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In July, 2023, polymyxin B sulfate for injection, an exclusive drug produced by a subsidiary of Shanghai Pharmaceutical Group, suddenly announced that it had dropped from 2,303 yuan/branch to 270 yuan/branch, with a drop of nearly 90%, which attracted the attention of the industry.

The reporter learned from official website, State Administration of Market Supervision, that the decision of administrative punishment on the case of abuse of market dominance by four companies, such as Shanghai Shangyao No.1 Biochemical Pharmaceutical Co., Ltd., was recently released. According to the decision, in July 2023, the Shanghai Municipal Market Supervision Administration initiated an investigation into the abuse of market dominance by four companies, including SAIC Biochemical. In December 2023, Shanghai Municipal Market Supervision Administration made an administrative punishment decision on this case according to law. The punishment decision shows that during the period from December 2017 to June 2023, four pharmaceutical companies abused the dominant position in the market of polymyxin B sulfate for injection in China, and implemented the behavior of selling preparations at unfairly high prices, which excluded and restricted market competition and harmed the interests of patients and social public interests.

Well-known anti-monopoly law experts pointed out in an interview that the above four companies were fined 1.219 billion yuan for violating the Anti-monopoly Law of the People’s Republic of China, which is the case with the largest amount of anti-monopoly punishment in the pharmaceutical field at present.

Monopolize the API market

Polymyxin B sulfate for injection plays an important role in the treatment of carbapenem-resistant gram-negative bacteria infection, which is highly dependent on hospitals and patients and difficult to be replaced by other drugs. Before 2017, no domestic company produced its raw materials and medicines and needed to import them from abroad.

According to the circular of the State Administration of Market Supervision, three private pharmaceutical companies, Wuhan Huihai Pharmaceutical Co., Ltd., Wuhan Kede Pharmaceutical Co., Ltd. and Hubei Minkang Pharmaceutical Co., Ltd., and the state-owned pharmaceutical company Shanghai Pharmaceutical Group Shangyao No.1 Biochemical Pharmaceutical Co., Ltd., abused the dominant position in the market of polymyxin B sulfate for injection in China and implemented the act of selling preparations at unfair high prices.

Wuhan Huihai, Wuhan Kede and Minkang Pharmaceutical (collectively referred to as Wuhan Huihai) have the same actual controlling shareholders, confused personnel and office locations, unified decision-making, division of labor and cooperation, jointly implemented the acts involved, and shared monopoly profits.

In order to introduce and control its raw materials, in 2010, Wuhan Huihai signed an agreement with Danish Yaseli Company to become the agent of Danish Yaseli China market. Since 2016, Wuhan Huihai has given the sales manager of Danish Yaseli China a benefit fee, asking him not to sell the API to other enterprises, thus controlling the supply of the whole API in China market.

On the other hand, Wuhan Huihai is busy looking for manufacturers. Because only the drug is qualified for production in China, it has not been put into production. Wuhan Huihaisui reached a cooperation intention with Shanghai Pharmaceutical Biochemical Co., Ltd. to supply raw materials to Shanghai Pharmaceutical Biochemical Co., Ltd., which was responsible for drug declaration and production, and granted exclusive distribution rights to its preparations, from which Shanghai Pharmaceutical Biochemical collected processing fees. Shanghai Pharmaceutical Biochemical applied for production qualification, and obtained the production approval from the Food and Drug Administration in 2017, becoming the only production enterprise in China.

According to the Shanghai Municipal Market Supervision Bureau, operators must first have APIs for R&D and production when entering the market, while Wuhan Huihai controls the supply of APIs in the China market, so it is difficult for other operators to obtain APIs. It is reported that this is the second time that Wuhan Huihai was punished by pharmaceutical antitrust in 2023. In May 2023, the State Administration of Market Supervision fined him 4,126,800 yuan. Wuhan Huihai Pharmaceutical Co., Ltd. was established in 2003 with a registered capital of 3 million yuan, and its legal representative is Li Meilin.

Conspire to earn excess profits

Shanghai Pharmaceutical Biochemical Co., Ltd. belongs to Shanghai Pharmaceutical Group, with total assets of 800 million yuan and registered capital of 225 million yuan.

When Wuhan Huihai signed a cooperation agreement with Shanghai Pharmaceutical Biochemical Co., Ltd., it was agreed that when bidding for preparations, the two sides would negotiate and communicate on matters such as bidding price and distributors, and jointly agree on bidding matters. According to the rules of drug sales, Shanghai Pharmaceuticals Biochemistry came forward to connect with the drug recruitment departments of all provinces in the country, made online quotations, and invoiced and sold them to circulation enterprises according to the instructions of Wuhan Huihai to obtain the sales income of preparations.

As the only operator who sells the drug, Shangyao Biochemical has the ability to influence and determine the key trading conditions such as sales price and sales quantity. The price of the drug was 2303 yuan/piece in Fujian province for the first time, and then it reached 2918 yuan/piece in Shanghai. Since then, the provinces have hung up their nets one after another, and the prices are mostly 2303 yuan/branch to 2918 yuan/branch. According to the instructions of Wuhan Huihai, Shanghai Pharmaceutical Biochemical Co., Ltd. supplies the goods to the circulation enterprises after deducting the distribution fee according to the hanging price.

In 2016, the state began to implement the "two-vote system" policy, that is, drugs are invoiced once from the production enterprise to the circulation enterprise and once from the circulation enterprise to the medical institution, with the aim of reducing the circulation of drugs and lowering the price of drugs. Limited by the "two-vote system", Wuhan Huihai can’t directly obtain the monopoly profit of preparation sales by buying low and selling high. To this end, Wuhan Huihai, with the cooperation of Shanghai Pharmaceutical Biochemical Co., Ltd., obtained monopoly profits from the raw materials link by inflating the sales price of raw materials.

Due to the large amount of payment for raw materials, Wuhan Huihai arranged for 38 pharmaceutical companies in Hubei and Jiangxi to increase prices step by step, and gradually pushed up the import price of raw materials purchased from Danish Yaseli Company from 73 yuan/g to 94 yuan/g to 18,000 yuan/g to 35,000 yuan/g, and sold them to Shanghai Pharmaceutical Biochemical Company to produce preparations, from which profits were made. This creates the illusion that the high drug price is due to the high drug price of raw materials.

Drive up drug prices for nearly six consecutive years.

According to the Shanghai Municipal Market Supervision Bureau, in 2022 alone, the illegal income of Wuhan Huihai was 610 million yuan, and that of Shanghai Pharmaceutical was 330 million yuan. The biochemical behavior of Wuhan Huihai and Shanghai Pharmaceutical Co., Ltd. constitutes the abuse of market dominance to sell goods at unfairly high prices.

It is reported that the cost of drug production is mainly composed of two parts: the cost of raw materials and the cost of biochemical workshop. According to the biochemical financial data of Shanghai Pharmaceutical Co., Ltd., the total production cost of this drug is about 8.6 yuan -14.6 yuan/piece, and the processing fee charged by Shanghai Pharmaceutical Co., Ltd. is from 140.4 yuan/piece -230 yuan/piece. Finally, the net price of the drug is as high as 2303 yuan/piece -2918 yuan/piece.

In addition, the domestic sales price of polymyxin B sulfate for injection is significantly higher than that of other countries and regions in the same period, which is about 35 to 44 times that of overseas products.

"The serious handling of this case corrected the illegal behavior in time, and the drug price dropped by nearly 90%. This safeguards the interests of consumers and the public interest. " In an interview, Wang Xianlin, a member of the Expert Advisory Group of the State Council Anti-monopoly Committee and vice president of china law society Economic Law Research Association, pointed out that the parties in this case abused their dominant market position to sell drugs at unfairly high prices. On the one hand, they distorted the market price formation mechanism of this drug and made its price seriously deviate from the normal level, which excluded and restricted market competition. On the other hand, it also makes patients have to pay higher prices, increases the cost of medication for patients, and seriously damages the interests of patients; It also increased the expenditure of the national medical insurance fund, which seriously damaged the public interest.

The reporter learned that after the above-mentioned case was investigated in July 2023, six senior executives of Shanghai Pharmaceutical Group were investigated. In September 2023, Pan Deqing, former vice president of Shanghai Pharmaceutical, Li Ping, general manager of Shanghai Shangke Pharmaceutical, Chen Binhua, former general manager of Shanghai Pharmaceutical Biochemical, and Huang Yuhui, former deputy general manager of Shanghai Pharmaceutical Biochemical, were investigated. In November, Zhou Jun, chairman of Shanghai Pharmaceutical, and Gu Haoliang, former vice president of Shanghai Pharmaceutical, were investigated.

CCTV News:Weihai Economic Development Zone in Shandong Province has a coastal industrial coastline of 19 kilometers. In recent years, the local area has fully tapped its development potential, cultivated leading enterprises and built an industrial cluster of offshore equipment.

At present, at the Weihai Shipyard in Jinling, China Merchants, the eighth ro-ro passenger ship is finishing its work.

Li Wenxiu, Technical Manager of 271 Ship of China Merchants Jinling Ship (Weihai) Co., Ltd.:The ship not only meets the latest requirements for safe return to Hong Kong, but also has the functions of waste heat recovery of main engine, waste heat recovery of air conditioner and zero discharge when berthing.

Weihai Economic Development Zone has a coastal industrial coastline of 19 kilometers. In recent years, they have focused on the development of high-end marine equipment and vigorously cultivated a number of leading enterprises such as Jinling Shipyard. The current order of the shipyard has been scheduled for 2028.

To ensure the development of key enterprises, Weihai Economic Development Zone implemented the system of leadership subcontracting and daily contact service, and the needs of enterprises quickly received attention. The Development Zone Management Committee coordinated the cooperation between Haida Logistics and the shipyard.

Wang Dengpan, Deputy Director of Economic Development Bureau of Weihai Economic Development Zone:The whole area of Haida Logistics Project is 30 mu, and the construction area is close to 20,000 square meters. After completion, no suitable project has been found, and the factory building is idle.

The two sides hit it off, initially reaching 5-mdash; Ten years of cooperation intention has fully released the production capacity of Jinling Shipyard. To cultivate high-end offshore equipment industry, the Economic Development Zone has also made efforts in industrial chain docking and investment promotion, reducing enterprise costs and promoting cluster development.

Wang Jinpo, Deputy Director of China Merchants Bureau of Weihai Economic Development Zone:Up to now, the production project of Shandong Electrician and submarine cable with an investment of 3 billion yuan has been signed and landed, and the production base of unmanned boats will start construction immediately.

[Episode 3: Returning with Full Load]

"Return" is the ultimate goal of Chang ‘e V, but every step on the way back faces many tests. This episode begins with the take-off from the lunar surface of the probe and tells the journey of Chang ‘e 5 to go home. Take-off on the lunar surface, space pursuit, the first unmanned rendezvous and docking of human beings in lunar orbit, the transfer of lunar samples and re-entry are both thrilling and exciting. On December 17th, the Chang ‘e V returner successfully landed in the scheduled area of Siziwangqi, Inner Mongolia.　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　

　　On April 20th, the journal Tumor Biology (hereinafter translated as Tumor Biology) under SAGE Publishing House in the United States issued a retraction statement, announcing that 107 papers written by China authors would be revoked, which were suspected of providing false peer review information in violation of regulations. Another international organization, The Committee on Publication Ethics (COPE), claimed: "These illegal operations seem to be planned by some third-party organizations, which provide such illegal services for the authors of papers."

　　107 articles were rejected by journals.

　　The reporter of Beijing Youth Daily saw on the website of Tumor Biology that the journal released a retraction statement on April 20th: "According to the recommendation of the Publishing Ethics Committee, publishers and editors decided to retract the manuscript. After a thorough investigation, we believe that the paper has violated the rules in the peer review process. "

　　In the retraction statement, the journal listed a statement posted on the website of the Publishing Ethics Committee, which stated: "The organization has realized that several journals belonging to different publishers have systematic and inappropriate manipulation in the peer review process. These operations seem to be planned by some third-party organizations, which provide this service for the authors of the papers. "

　　According to the reporter of Beiqing Daily, Oncology Biology is the official magazine of the International Society of Oncology and Biomarkers, which once belonged to Springer-Verlag Publishing House. The website introduces its impact factor as 2.926. Springer Publishing House is one of the largest scientific and technological publishing houses in the world, which is famous for publishing academic publications. At the end of 2016, "Tumor Biology" was transferred to American SAGE Publishing House. Since January this year, American SAGE Publishing House has started publishing this journal.

　　The author of the withdrawn manuscript involves many hospital doctors.

　　The reporter of Beiqing Daily noticed that there were 107 papers mentioned in Tumor Biology that were withdrawn, involving many cities in China. Most of the authors are hospital doctors, and their institutions are affiliated hospitals of domestic universities, including Zhejiang University Affiliated Hospital, Shanghai Jiaotong University Affiliated Hospital, Jinan Central Hospital affiliated to Shandong University, Xiangya No.1, No.2 and No.3 Hospitals and other well-known hospitals.

　　Yesterday, the reporter of Beiqing Daily tried to contact the author of the withdrawn paper listed in the journal. Among them, among several authors published in Regulation of Activating Protein-4-Associated Metastases of Non-Small Cell Lung Cancer Cells by Mir-144 in 2016, Zhang Zefeng, deputy chief physician of the Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University, admitted that he had published a paper in Tumor Biology at the same time, but he said that he only participated in the relevant research as a member of the scientific research team, and he was not clear about the specific process of publishing the paper. Liu Junfeng, another chief physician of the hospital, refused the interview on the grounds that the identity of the reporter could not be verified.

　　Peer review is accused of fraud.

　　In a statement issued by the Publishing Ethics Committee, it was mentioned: "Some institutions that provide services for authors to publish papers are suspected of fraud in peer review."

　　Peer review mentioned in the retraction statement is a kind of review procedure, and the publishing unit will choose whether to accept the manuscript or not by this method. The specific operation is to let other experts and scholars in the same field review the academic works to be published. In the peer review, the real names and e-mail addresses of experts and scholars participating in the review need to be provided, and the editorial department of academic journals will confirm the review opinions to these experts and scholars by e-mail.

　　Although the names of the peer-reviewed experts of 107 papers that have been rejected are true, their e-mail addresses are suspected to be false. Because many experts who mentioned their names, publishing institutions have their e-mails, which can’t match the e-mail addresses provided in these papers.

　　An industry insider who has been engaged in peer review told the reporter of Beiqing Daily that the editorial department was not sure whether the review comments were true because it was suspected that the email address of the review experts was false.

　　The industry believes that these papers with suspected problems did not fulfill their review duties at the beginning of publication. Because even if the author of the paper provides false peer review information, the editorial department of the journal can contact the experts and scholars who are named for review to verify it, because many of those experts and scholars are in the expert database of academic journals, but they have not verified it.

　　The reporter of Beiqing Daily noticed that in August 2015, springer announced the withdrawal of 64 papers published in its 10 academic journals, all of which were from China authors. As early as March 2015, British publishing house BMC announced the withdrawal of 43 academic articles, 41 of which were written by China. In these two cases, publishers gave reasons for "suspected fraud in peer review".

　　A doctor in the affiliated hospital of Zhejiang University, who asked not to be named, said that no matter how busy the doctor is, he can’t find a third-party agency to represent the paper. "Under normal circumstances, our contributions to international journals are carried out in the journal official website, and we operate in the order of instructions. The paper intermediary is unreliable. If something goes wrong, even the doctor may not be able to do it. Once the paper is considered fraudulent, it will be ruined. "

　　Text/reporter Guo Linlin Intern reporter Xu Lina Liu Sijia

　　Xinhua News Agency, Shanghai, March 28th Title: Legal interpretation of Wu Xiaohui’s case — — Interview with Professor Ruan Qilin of China University of Political Science and Law

　　Xinhua News Agency reporter Chen Fei, Huang Anqi

　　On March 28th, the Shanghai No.1 Intermediate People’s Court held a trial in the first instance to hear the case of Wu Xiaohui, the former chairman and general manager of Anbang Property Insurance Group Co., Ltd., who was suspected of fund-raising fraud and duty embezzlement. Weibo, the official of Shanghai No.1 Intermediate People’s Court, made a summary of the trial. The reporter interviewed Professor Ruan Qilin, an expert in criminal law and China University of Political Science and Law, and asked him to analyze and interpret the main legal issues involved in this case according to the facts and evidence of the case published by Guan Wei of Shanghai No.1 Intermediate People’s Court, as well as the relevant information published by relevant departments and media before.

　　Reporter: From the main criminal facts and evidence that the procuratorate accused the defendant of being suspected published by Weibo, the official of Shanghai No.1 Intermediate People’s Court, how do you think to evaluate the nature of these behaviors of the defendant in criminal law? What kind of serious social harm do these behaviors have?

　　Ruan Qilin: Defendant Wu Xiaohui used Anbang Property Insurance as a financing platform, and the amount of illegally selling investment-type insurance products exceeded the scale approved by the China Insurance Regulatory Commission, reaching more than 720 billion yuan, which was illegal. According to Article 1 of the Supreme People’s Court’s Interpretation on Several Issues Concerning the Specific Application of Laws in the Trial of Illegal Fund-raising Cases, (1) those who, without the approval of the relevant departments according to law, (2) publicize in the society, and (3) promise to repay the principal and interest or pay a return, and absorb funds from the public are illegal to absorb public deposits. Although Anbang Property Insurance controlled by Wu Xiaohui has been approved by the relevant departments to issue investment-type insurance products according to law, it is far beyond the scale of sales approved by the China Insurance Regulatory Commission (over-raised), and the over-raised part should be considered as "not approved by the relevant departments according to law", which is illegal. Its over-raised part is staggering, reaching more than 720 billion yuan, which contains great financial risks and has extremely serious social harm.

　　Defendant Wu Xiaohui, in the above-mentioned illegal fund-raising process, first, used deception to secretly increase the capital of Anbang Group and Anbang Property Insurance by over-raised premium funds of more than 77 billion yuan. According to the relevant regulations, shareholders must increase their capital to insurance companies with their own funds, and Wu Xiaohui secretly converted the premium funds raised in excess into shareholders’ funds as capital increase for Anbang Property Insurance and Anbang Group, which violated the law and invented solvency to the CIRC and the public. At the same time, Wu Xiaohui manipulated Anbang Group and Anbang Property Insurance to modify profits, adjust data, disclose false information, and continue to make false propaganda to the public. Deceive the public to buy its investment insurance products, resulting in a sharp expansion of the scale of over-raising. Second, illegal possession of huge illegal fund-raising funds (over-raised premiums). After Anbang Property & Casualty sold investment insurance with a predetermined income in its own name, according to Wu Xiaohui’s request, it concealed the over-raised premium to Anbang Group or transferred it to the industrial company actually controlled by Wu Xiaohui, leaving the supervision of the China Insurance Regulatory Commission and other regulatory authorities, thus realizing the purpose of Wu Xiaohui’s illegal possession of huge premium funds by himself or through the industrial company actually controlled by himself, and actually causing a fund gap of 65.2 billion yuan. Wu Xiaohui can only repay the old premium gap with new premium income, and so on, with the Ponzi scheme. According to Article 192 of the Criminal Law, "those who illegally raise funds by deception for the purpose of illegal possession … …” It constitutes a crime of fund-raising fraud.Wu Xiaohui used deception to illegally raise funds and illegally took some of the funds for himself, which was suspected of constituting a crime of fund-raising fraud.

　　At the same time, the defendant Wu Xiaohui took advantage of his position to instruct others to transfer the original Anbang property insurance premium to the industrial company he actually controlled for his own use by means of transfer without accounting, which met the constitutive requirements of the crime of occupational embezzlement, and the amount was 10 billion yuan, which was extremely huge.

　　Reporter: We noticed that the defendant’s illegal fund-raising behavior in this case was carried out by insurance institutions. In judicial practice, how to determine the illegality of the actual controller using legal financial institutions to raise funds illegally? How to identify its criminal purpose? How to distinguish between unit crime and individual crime of natural person?

　　Ruan Qilin: These questions you asked are very professional. First of all, about the illegality of this behavior. Although Anbang Property Insurance is a legal financial institution, its issuance of investment-type insurance products must be approved by the CIRC according to relevant regulations. It is illegal to sell investment insurance products without the approval of the CIRC or beyond the sales scale approved by the CIRC. Because super-scale sales and illegal fund-raising have the same financial risks and are equally harmful to investors. Moreover, because it is a legal financial institution, it is easier to gain the trust of the public, and it can quickly expand the scale of illegal fund-raising to form greater financial risks, which is more harmful to society. The scale of illegally raised funds in this case has rapidly expanded to more than 720 billion yuan, which is closely related to Wu Xiaohui’s use of the signboard of Anbang Property Insurance legal financial institutions. After the incident, the relevant government departments immediately took over Anbang Group, which reflected the seriousness of the financial risks it created and forced the government departments to take over. In recent years, illegal fund-raising cases, such as the largest "Easy Rent Treasure" case, involved only tens of billions of yuan, which is a drop in the bucket compared with the scale of illegal fund-raising in this case. The amount that this case was illegally occupied and could not be returned reached more than 65 billion yuan, far exceeding the fund-raising fraud cases such as "Easy Rent Treasure".

　　Secondly, about the defendant’s criminal purpose. According to Article 2 of the Supreme People’s Court’s Interpretation on Several Issues Concerning the Specific Application of Laws in the Trial of Illegal Fund-raising Cases, if illegal fund-raising by deception has one of the following circumstances, it can be considered as "for the purpose of illegal possession": (2) wantonly squandering fund-raising funds, resulting in the non-return of fund-raising; … … (5) Evading, transferring funds, concealing property and evading the return of funds; … … (8) Other circumstances in which the purpose of illegal possession can be identified. In this case, the defendant used fictitious equity investment, false shareholder dividends and other means to transfer the investment-type insurance product funds raised by Anbang Property Insurance to the industrial company actually controlled by him for possession and use, and has caused more than 65 billion yuan of premium funds to be returned. Enough to identify the purpose of illegal possession.

　　Third, whether it is a unit crime or an individual crime. This case should be considered as an individual crime such as the defendant, and should not be considered as a unit crime. First, the unit crime should reflect the unit will, while the management of Anbang Group, Anbang Property Insurance and other Anbang companies all reflect Wu Xiaohui’s personal will, which does not conform to the company’s operating rules and cannot make Wu Xiaohui’s personal will rise to the unit will. Second, the essential feature of unit crime is "for the benefit of the unit". A large number of facts in this case show that Wu Xiaohui made a personal decision and sought personal interests. According to Article 3 of the Supreme People’s Court’s Interpretation on Relevant Issues Concerning the Specific Application of Law in the Trial of Unit Crimes: "Whoever embezzles the name of a unit to commit a crime, and the illegal income is divided among the individuals who commit the crime, shall be convicted and punished in accordance with the provisions on crimes committed by natural persons". In this case, Wu Xiaohui illegally took tens of billions of premium funds for himself, which should be considered as a natural person crime. At the same time, in this case, Zhongyuan Anbang Property Insurance and Anbang Group had to bear the responsibility of paying more than 720 billion yuan of wealth management products illegally raised by Wu Xiaohui and others because of their illegal fund-raising and illegal possession of premium funds. It has suffered huge economic losses and financial risks, and it is also a victim.

　　Reporter: Generally, fund-raising fraud cases will cause great losses to fund-raising participants, but there is no actual loss of the insured in this case. Excuse me, Professor Ruan, does this situation affect the criminal evaluation?

　　Ruan Qilin: Actually, Anbang Property Insurance has already taken great risks. According to today’s trial, the total assets of Wu Xiaohui’s personal and industrial companies at the time of the incident were far below the funding gap. Wu Xiaohui has hollowed out Anbang Property Insurance by using false capital injection, false investment, and various pretexts to transfer premiums. Once the capital chain breaks, millions of investors will suffer huge losses. Fortunately, the government supervision department found the huge redemption risk in time, took over Anbang Group urgently, and went all out to prevent the risk from expanding. That is to say, the actual loss of investors has not yet occurred in this case, which is entirely due to the fact that the government regulatory authorities prevented Wu Xiaohui and others from committing crimes of illegal fund-raising and taking over Anbang Group. This should not reduce Wu Xiaohui and others’ guilt of encroaching on the original Anbang property insurance and Anbang Group property, using fraudulent methods to illegally raise funds and illegally occupying fund-raising funds.

　　Reporter: Wu Xiaohui’s two criminal facts in the prosecution are that he took the funds of financial institutions as his own, but some of them were identified as fund-raising fraud and some as duty crimes. Why are these two parts of criminal facts evaluated differently in law? Why can’t it be regarded as the crime of illegal use of funds?

　　Ruan Qilin: In the case of basically the same criminal modus operandi, the public prosecutor found that Wu Xiaohui constituted the crime of fund-raising fraud and the crime of occupational embezzlement respectively. The criteria for such identification were based on the nature of illegally occupied funds.

　　Generally speaking, after an investor buys the products of an insurance company, the funds are actually owned and controlled by the insurance company, and the actual controller’s transfer of possession by taking advantage of his position should be regarded as a duty crime or a crime of illegal use of funds. All the illegally occupied funds come from Anbang’s legal premium income.

　　In order to obtain a large amount of funds, the actual controller used financial institutions as a tool to illegally absorb funds from the public. For example, in this case, Wu Xiaohui sold investment-type insurance products beyond the scale approved by the China Insurance Regulatory Commission, which was illegal in fund-raising, and the defendant illegally transferred and occupied the huge amount of funds in illegal fund-raising. The illegally occupied funds came from the premium funds of investment products that Anbang had overpaid (illegally raised funds). In illegal fund-raising, using deception to illegally raise funds and transfer the illegal fund-raising funds for possession is a related act under the deliberate control, that is, illegal fund-raising and illegal possession of fund-raising funds, which cannot be divided and should be evaluated as a whole. Therefore, it is reasonable to identify this part as fund-raising fraud.

　　The crime of illegal use of funds is the illegal use of funds managed by the relevant management institutions in violation of state regulations. This crime cannot cover or include illegal sources of funds and illegal possession of funds. Wu Xiaohui, the defendant in this case, used Anbang Property Insurance to sell insurance products beyond the approved scale, which was illegal fund-raising, and this illegal fund-raising behavior could not be included in the crime of illegal use of funds. That is to say, the crime of illegal use of funds can only evaluate the illegal use of funds, but it cannot or is not enough to evaluate the illegal source of funds, that is, it cannot include the evaluation of illegal fund-raising behavior. For Wu Xiaohui’s illegal fund-raising behavior, only the crime of illegally absorbing public deposits or the crime of fund-raising fraud can accurately evaluate the illegality of his obtaining funds. In addition, the crime of illegal use of funds can not cover the illegal possession of funds, and the crime of fund-raising fraud can include not only the illegal acquisition of funds, but also the illegal possession of illegally acquired funds, as well as the domination, use and punishment on the basis of illegal possession. Therefore, only the crime of fund-raising fraud can completely evaluate Wu Xiaohui’s illegal fund-raising and illegal possession of illegally raised funds. If the crime of illegal use of funds is found, the evaluation of its illegal fund-raising and illegal possession of funds is omitted, and all its behaviors are not completely evaluated.

What is the current automobile market? 26,900, you can buy a car.

Just now, it went on the market. As a pure electric mini-car, Pentium Pony has three models, one of which has a battery life of 122km and the other two have a battery life of 170km, and the price ranges from 26,900 to 31,900 yuan.

What is the biggest highlight of this car? Obviously, it is cheap. Moreover, no matter from the appearance or publicity, the positioning of this car is very clear, that is, female consumers who have just entered the society and bought cars for the first time. So is this car worth buying? Today we will analyze it.

122km and 170km, who should I buy?

In terms of price, the price of the 122km cute horse is 26,900 yuan, and the price of the 170km energetic horse is 29,900 yuan, and the difference is only 3,000 yuan. So what’s the difference?

The most obvious is the difference in battery life. One is 122km, and the other is 170km. What else?

It is worth mentioning that all three models of Pony do not support fast charging. The charging time of 122km Mengqu Horse is 5.2 hours, and that of 170km Yuanqi Horse is 6.5 hours.

There is no difference between them except energy density.

Then, compared with the price difference of 3,000 yuan, we still think that the price-performance ratio of the 170km Yuanqi horse model is higher.

Which of the two 170km models is more cost-effective?

Let’s look at the price first. The price of a 170km energetic horse is 29,900 yuan, and the price of a 170km energetic horse is 31,900 yuan. The difference between the two cars is only 4000 yuan.

So what is the difference between the two cars under the premise of the same battery life?

In fact, it is some more detailed configurations, such as the reversing image that the 170km Yuanqi horse does not have, and the full LCD instrument is carried on the dynamic horse model; Moreover, the Yuanqima model is only equipped with one front USB interface, but the vitality is equipped with two interfaces immediately; The number of speakers has also changed from one to two.

In that case, in fact, I think the most useful configuration of vitality immediately is the reversing image, so I think that the 170km models are very cost-effective, but it is a good choice to spend 31,900 yuan on the top version.

Therefore, if we recommend it, we think that 170km is worth buying than 122km, and among the 170km models, the high-powered horse is more cost-effective.

And if you buy a car now, you can also enjoy a series of rights and interests. For example, discount interest and various subsidies, and you can also enjoy two years of original value repurchase, etc., which can basically be said to minimize the cost of car purchase, and it is also considered more comprehensively for young people.

Summary:

Generally speaking, Pentium Pony has cut into the entry-level car buying range at a very low price, so that many young people who have just entered the society have the opportunity to drive a car that can shelter from the wind and rain, and from the configuration point of view, this car is also sincere. I believe this car will be a car of FAW Pentium that undertakes the task of walking.

So what do you think of this car? Welcome to leave a message for discussion.

　　CCTV News:The Central Meteorological Observatory continued to issue a cold wave orange warning at 18: 00 on December 14th. Affected by strong cold air, it is estimated that the temperature will drop by 8 ~ 12℃ from west to east and from north to south in most parts of China from 20: 00 on December 14th to 08: 00 on December 17th, among which the temperature will drop by 14 ~ in central and northern Shaanxi, northwestern and western Shanxi, central Inner Mongolia, northern Hebei, northwestern Shandong, eastern Liaoning, southeastern Jilin, eastern Jianghuai, most of the south of the Yangtze River, southeastern Southwest China and most of southern China. Most of the above areas are accompanied by northerly winds of 4-6 grades, with gusts of 7-9 grades and local winds exceeding 10 grades. There are 6-8 grades and gusts of 9-10 grades in the eastern and southern seas. On the morning of 17th, the lowest temperature line of 0℃ can be pressed south to southern Guizhou and northern Jiangnan, and the line of -10℃ is located from northern Huanghuai to Qinling. The lowest temperature in some areas of North China and northern Huanghuai will approach or reach the historical extreme value in the same period.

　　Defense guide:

　　1, the government and relevant departments shall, in accordance with their duties, do a good job in cold wave emergency work;

　　2. Pay attention to cold and warmth;

　　3, agriculture, aquaculture, animal husbandry, etc. should actively take anti-frost, freezing and other cold measures to minimize losses;

　　4, do a good job of windproof.

　　Central Meteorological Observatory (in China)twelvemoon14sun18timecontinueissueicefreezeyellowColor warning:

　　It is estimated that there will be freezing rain in parts of southern Henan, western and northeastern Hubei and western Anhui from 20: 00 on December 14th to 20: 00 on 15th.

　　Defense guide:

　　1, transportation, public security and other departments should do a good job in preparing for road icing in accordance with their duties;

　　2. The electric power department should prepare for the deicing of power facilities;

　　3. Take certain protective measures for crops, vegetables, flowers, fruits and forestry;

　　4. Pedestrians should pay attention to anti-skid when going out.

　　Central Meteorological Observatory (in China)At 18: 00 on December 14,Issue a blue warning for blizzard:

　　It is estimated that there will be heavy snow in parts of eastern Jilin, eastern Liaoning, southwestern Shandong, southern Henan and northwestern Hubei from 20: 00 on December 14th to 20: 00 on December 15th, among which there will be heavy snow (10 ~ 12mm) in eastern Jilin and eastern Liaoning. The depth of newly added snow in some areas above is 5-7 cm, and the local area is more than 9 cm.

　　Defense guide:

　　1. The government and relevant departments shall, in accordance with their duties, make preparations for snow disaster prevention and freezing injury prevention;

　　2 transportation, railway, electric power, communications and other departments should carry out road, railway and line inspection and maintenance, and do a good job in road cleaning and snow melting;

　　3. Pedestrians should pay attention to cold prevention and anti-skid, drivers should drive carefully, and vehicles should take anti-skid measures;

　　4. Farming and pastoral areas and breeding industries should reserve feed and prepare for snow disaster prevention and freezing injury prevention;

　　5. Reinforce temporary structures that are easily crushed by snow, such as scaffolding.

　　Central Meteorological Observatory (in China)twelvemoon14sun18timecontinueIssue a gale blue warning:

　　It is estimated that from 20: 00 on December 14th to 20: 00 on 15th, there will be strong winds with grades 5-6 and gusts 7-8 in parts of western Inner Mongolia, central and western Liaoning, southern Xinjiang basin, western Tibet, eastern and southern Qinghai, Hexi in Gansu, northwestern Shaanxi, southwestern Shanxi, eastern Shandong and northern Sichuan Plateau, among which there are grades 7 in southern Xinjiang basin, northern and western Tibet and eastern and southern Qinghai. There will be strong winds of 7-8 grades and gusts of 9 grades in the Bohai Sea, the Bohai Strait, most of the Yellow Sea and the western part of the East China Sea.

　　From 20: 00 on December 15 to 20: 00 on December 16, there were strong winds of 5~6 and gusts of 7 in central Inner Mongolia, southern Xinjiang basin, central and western Tibet and southern Qinghai, among which there will be strong winds of 7 and gusts of 8 in southern Xinjiang basin, northern Tibet and southwest China; The Bohai Sea, Bohai Strait, most of the Yellow Sea, most of the East China Sea, the east of Taiwan Province Strait, bashi channel, Taiwan Province, the northern South China Sea and Beibu Gulf will have strong winds of magnitude 7-8 and gusts of magnitude 9, among which the winds in parts of the Taiwan Province Strait and bashi channel can reach magnitude 9 and gusts of magnitude 10.

　　Defense guide:

　　1. The Central Meteorological Observatory and China Maritime Search and Rescue Center remind ships sailing and operating in the sea areas affected by strong winds to pay attention to navigation safety;

　　2, forest, grassland, urban fire departments to prepare for fire prevention, airport, railway, highway and other traffic management departments should take measures to ensure traffic safety;

　　3, stop high altitude, water outdoor work and recreational activities, reinforcement or proper placement of hoardings, scaffolding billboards, simple facilities and other structures that are easily blown by strong winds;

　　4. Pedestrians and vehicles should not stay in temporary buildings such as tall buildings and billboards, or under trees.

Where to go for leisure and entertainment during the Spring Festival holiday? Shijiazhuang’s characteristic commercial district has prepared a rich consumption feast, which makes you feel the rich flavor of the year and experience the charm of traditional culture.

■ Wanli Temple Pedestrian Street

First, the activity time:

From New Year’s Eve on January 21st to the sixth day of January 27th, the Spring Festival holiday lasts for 7 days.

Second, the activity content:

Theme 1: Theme activity of "Opening the New Year with Beautiful Companion"

1. Meet the "rabbit" auspicious Wanli Temple and spend the auspicious year with you at the Spring Festival Cultural Temple Fair.

Time: December 31st-February 5th　

Venue: Wanlimiao Square+Tongle Street

2. Play in the world of ice and snow-ice carnival

Snow hills, snow circle slides, snowmobiles, snowmobiles, snow walks … Hey, play nonstop.

Time: December 26th to February 5th.　

Venue: Water Curtain Square

Theme 2: A series of ethnic and folk activities of "Culture Enters Thousands of Families, Not Leaving the Legacy for the New Year"

1. "Welcome the New Year to celebrate the New Year" and the closing ceremony of the colorful weekend.

(1) Special performance by the library team.

Special performance of dance models: January 14th.

Special performance of Beijing Opera Fans Association: January 15th.

Zhang Yong Famous Artists Studio Instrumental Performance Time: January 31st.

(2) Comprehensive high-end cultural performances (performance unit: Love Art Troupe)

The performance time of "Jade Rabbit Making New Year" variety show: the evening of January 26th (the fifth day of the first month).

The performance time of "Jade Rabbit Making Lantern Festival" variety show: February 5th (Lantern Festival) night.

■ Ximeihua Street Lane Characteristic Commercial Pedestrian Street

Flower Young new year collection season 1

I. Activity time: January 7-January 21, a total of 15 days.

2. Location: Hibox Block

Third, the way of publicity: radio, WeChat, LED, advertising space in the venue.

IV. Activities:

During the Spring Festival, the operation department will organize 30-50 Chinese New Year folk customs and people’s livelihood necessities merchants to set up stalls in Hibox block. This kind of goods have the characteristics of value-added, characteristics, traditional craftsmanship, intangible cultural heritage and so on, such as: traditional Chinese New Year’s goods, folk culture, collars, fish fishing, popcorn, hand-weaving, cooking oil, bagged rice, famous wine, gift boxes, meat, cooked food, fruits and vegetables, miscellaneous grains, and so on.

■ Wangquan Ancient Street

First, the activity time:

January 8, 2023 (the seventeenth day of the twelfth lunar month)-February 6, 2023 (the sixteenth day of the first lunar month)

2. Venue: Wangquan Ancient Street and Weidong Hutong

Iii. Activities:

During the Spring Festival holiday in Wangquan Ancient Street, modeling scenes, online celebrity punch points and special areas of the New Year Festival were set up to increase the atmosphere of the New Year in the neighborhood. Hold a variety of cultural and entertainment activities, and introduce a large number of special snacks. A cultural market to welcome the Spring Festival was held years ago, and Wangquan Jitu celebrated the Spring Festival during the Spring Festival.

1. Welcome the Spring Festival Cultural Market

(1) Time: January 8 to 20, 2023

(2) Location: Outside the service road of Wangquan Ancient Street

(3) Activity content: On the basis of the traditional Spring Festival neighborhood atmosphere, add fashion trend elements, introduce high-quality formats, and create a high-quality new year collection.

(4) format:

Traditional non-legacy: paper-cutting, wooden rotation and crochet;

Special snacks: making cakes, sugar people, rice cakes, retort cakes, etc.

Festive decorations: couplets, snuff, window grilles, lanterns, etc.

Layout map of waipai block: (including stalls and amusement areas)

2. Wangquan is the most delicious and Longxing celebrates the New Year.

(1) Time: January 21st, 2023 to February 6th, 2023.

(2) Scene atmosphere: In order to welcome the arrival of the Spring Festival, Wangquan Ancient Street is decorated with a wide range of Spring Festival atmosphere, with the theme of auspicious rabbits welcoming the spring; Merchants in the whole street posted Spring Festival couplets and hung red lanterns; Indoor promotion of Chinese New Year activities;

(3) Amusement: large-scale theme amusement facilities and recreational activities.

(4) Performing Arts: Spring Festival Cultural Performance of Wangquan Ancient Street Dance Stage; Non-legacy performances in the neighborhood, including Changshan drums, walking on stilts, running donkeys, etc.

(5) Parade: "Spring Festival Temple Fair Parade" in cooperation with Longxing Temple;

(6) Exhibition: Hanfu Parade Exhibition, Cosplay Theme Parade Exhibition, and Ancient Street Characteristic Theme Exhibition;

(7) Market: non-legacy exhibitions and sales, including tanghua, Latin films, metal crochet, imitation fur, etc. Special snacks are on sale, including fried skewers, drinks, candied haws and marshmallows.

■ Nanguan Ancient Town

1. Organize a food festival during the Spring Festival from January 21st to January 28th, 2023. During the event, organize cultural performances such as blessing in the New Year, crossing Hanfu, dancing the ancient city and celebrating the New Year with the Golden Lion.

2. On January 26th, 2023, cheongsam catwalk actors were invited to give visitors an immersive travel experience, and various cultural performances were used to set off the New Year atmosphere during the catwalk.

3. From January 26th to January 31st, 2023, traditional non-genetic inheritors were invited to show China’s traditional non-legacy performances and live shows in the block, covering shadow play, tanghua, Latin films, paper-cutting, gourd pyrography, etc.

■ Hutuo Wharf Pedestrian Street "Fuyun Yutu" Food Festival

1. New Year’s Day activities to benefit people’s livelihood

Time: January 1st (the 10th day of the twelfth lunar month)-February 6th (the 16th day of the first month).

Venue: Hutuo Wharf Pedestrian Street, Yijiayue City Plaza, Yijiayue Shopping Mall

2. "Chinese calligraphy welcomes New Year’s greetings to thousands of families" writes the Spring Festival couplets to send blessings.

Time: January 13th, 2023 (9: 00 -11: 00 am on the 22nd of the twelfth lunar month)

Venue: Hutuo Wharf Pedestrian Street

3. "Ruitu Chengxiang" is obliged to write couplets for the masses.

Time: January 13th (22nd of the twelfth lunar month)-January 19th (28th of the twelfth lunar month).

Venue: Art Museum, Confucian Temple, townships.

4. Illustrated Shijiazhuang Art Works Tour Exhibition

Time: January 23rd (the second day of the first month)-February 5th (the fifteenth day of the first month).

9: 00-11: 30 am; 2:00-5:00 p.m.

Venue: Art Museum

5. A special performance of pendant.

Time: January 25th (the fourth day of the first month)-January 28th (the seventh day of the first month).

10: 00-11: 30 am; 2: 00-3: 30 pm

Venue: Recreation and Sports Square

6. Ice and Snow Games

Time: January 25th (the fourth day of the first month)-February 7th (the seventeenth day of the first month).

Venue: West of Hutuo River South Bridge

7. "New Year’s Celebration" activity

Time: January 25th (the fourth day of the first month)-February 5th (the fifteenth day of the first month) 9: 00-11: 30 am; 2:00-5:00 p.m.

Venue: Confucian Temple, North Pole Station

8. "Jitu Happy New Year" sends culture to the countryside.

Time: January 30th (9th day of the first month)-February 4th (14th day of the first month).

Location: Mapu Village, Tiegan Town, the ninth day of the first month, Beiliujiazhuang Village, Zhaoba Town, the eleventh day of the first month, Gengzhuang Village, Daqiaotou Town, Nanying Village, Baizhuang Township, and Yangcun Village, Liucun Township, the fourteenth day of the first month. Performance time: 10: 00-11: 30 am; 2:00-3:30 p.m.

9. "Non-legacy makes the Spring Festival"-non-legacy and folk art exhibition activities

Time: January 25th (the 4th day of the first month)-February 5th (the 15th day of the first month).

9: 00 am-12: 00 am; 2:00-5:00 p.m.

Venue: Hutuo Wharf Pedestrian Street

10. China Chess Competition

Time: January 28th (the seventh day of the first month)

Venue: National Fitness Center

11. "Everyone reads-all people read" Spring Festival red reading activities.

Time: January 28th (the seventh day of the first month)-February 7th (the seventeenth day of the first month).

8: 30-12: 00 am; 1:30-5:00 pm

Venue: Library

12. Billiards Competition

Time: January 30th (the 9th day of the first month)

Venue: Zhanyun Billiards Club

13. The folk flower show will be concentrated in the city.

Time: February 2 (8: 30 am -11: 30 am on the twelfth day of the first month)

Venue: Xiangyang Street (Fuqian Road-Binhe Road)

14. Photo Exhibition of "Learning from the Top 20, Always Walking with the Party and Striving for a New Journey"

Time: February 2-February 5

Venue: Shenze County Sports and Culture Square

15. Table tennis match

Time: February 3rd (13th day of the first month)

Venue: National Fitness Center

16. "Lantern Festival in solve riddles on the lanterns" activity

Time: February 5th (15th day of the first month)

Venue: Hutuo Wharf Pedestrian Street

17. Cycling Competition

Time: February 10th (20th day of the first month)

Venue: Hutuo River Landscape Road

18. Exquisite Painting and Calligraphy Exhibition of "Jin Hu Farewell the Old Year and Welcome the New Year with Jade Rabbit"

Time: February 10th (20th of the first month)-March 11th (20th of February).

9: 00-11: 30 am; 2:00-5:00 p.m.

Venue: Art Museum

19.5km walking (running) activity

Time: February 15th (25th day of the first month)

Venue: Hutuo River Landscape Road

20. Basketball Invitational Tournament

Time: February 18th (January 28th)

Venue: Lize Square

21. "Everybody Dance-Fitness Dance (Fuck)" Competition

Time: February 21st (the second day of February)

Venue: Shenze Grand Theatre

■ Characteristic Pedestrian Street of Phoenix Sleepless City in Gaoyi County

Visit traditional temple fairs and watch folk performances.

I. Activity Time: December 31, 2022-January 15, 2023

2. Location: Liuxiu Park

Iii. Activities:

Folk stilts, steel spears stabbing throat, monkey show, two ghosts wrestling, magic acrobatics, etc.

1. From January 22nd to February 8th, watch the non-legacy iron flower for free at 21pm every day;

2. From January 21st to February 5th, the original price of 98 yuan Royal Circus tickets is 39.9 yuan; The original price of 68 yuan Royal Circus tickets is 29.9 yuan, with 3-6 performances every day;

3.1.15-The end of the snow season, the original price of the 98 yuan snow play package is the current price of 58 yuan; The original price is 19.9 yuan. The current price of tickets for Snow Park is only 9.9 yuan;

4. The original price of Tongqu Square 110 yuan amusement package is 29.9 yuan;

5. More than 120 uninterrupted real-life performances and temple fair performances in the whole day are free to watch.

■ Ole Northland

Auspicious, Happy New Year, Xinyi Beiren Happy Year

Activity content: Golden Rabbit Nafu welcomes the Year of China.

1. More than 100 famous brands are as low as 30% off in the new year’s holiday season, and you can enjoy more discounts.

2. The Spring Festival Garden has a strong Spring Festival atmosphere, and the New Year is blessed with good luck!

3. Carnival Parade, Ole Modern Clown Corps New Year Carnival Parade!

4. Open the door, dance the lion to welcome the spring, open the door to receive blessings and celebrate the New Year!

5. Rabbit flies into 2008-2023 Northern Ole New Year Joy Club!

■ Tumen Pass Post Town

Activity theme:

Pick up the flavor of the new year, and you will not be left behind.

Activity time: January 12-20

Activity content:

1. The opening ceremony of the fifth lantern show in Tumenguan: lighting the guard of honor and striking iron flowers;

On February 14th, Luquan District Folk Culture Festival opened, and there was a collection of new year’s goods.

3. Ice and Snow Festival (opening of Snow Park);

The above activities are from childhood to the fifteenth day of the first month.

Activity theme:

The Millennium Tumen happy ever after Spring Festival is not closed and lively.

Activity time: the first day to the fifteenth day of the Spring Festival.

Activity content:

1. New Year Lantern Festival, showing the Millennium Tumen, happy ever after;

2. Spring Festival activities: the God of Wealth and the Rabbit celebrate the New Year, and folk performances celebrate the New Year.

3. The whole first month activities: iron flower, traditional lantern ceremony and your legend performance.

■ Baili Water Town

"Happy New Year, Happy Water Town in Baili"

First, the activity time:

January 14-February 6, 2023 (24 days in total)

Second, the venue:

Dafudi and Shangjie

Third, the theme of the event:

Traveling in the snow and ice is happy for the New Year.

IV. Activities:

Step 1 have a reunion dinner

(1) Bai Li Bai Wei family banquet

The restaurant offers different standard family banquet menus, and the dishes are named and set with Chinese New Year elements. Provide basic services for individual customers during the event.

(2) jiaozi activities.

The event is only available for table meals for 8 or more people. The restaurant provides basic materials for wrapping jiaozi, and the restaurant processes them free of charge after tourists wrap them on site.

(3) The God of Wealth sends blessings

Arrange the staff to wear the costumes of the God of Wealth at random, and distribute red envelopes to the elderly and children, including blessing words and small coupons.

2. Stay at a homestay in Huaxiang (this activity is only for customers staying at the homestay, and it will stimulate the sales of the homestay through exclusive activities. )

(1) Dress up your "home"

Customers can get Spring Festival decoration materials from the front desk when they check in. Customers are encouraged to stick Spring Festival couplets, stick window grilles and hang lanterns in their rooms. Invite the housekeeper to take a family photo for him. After the photo is sent to a circle of friends, you can get a blind box for the New Year.

(2) Folklore Experience/Bailibai New Year

Before the Spring Festival, we will carry out special experience activities according to folk customs, such as making candied haws with twenty-three candied melons; Years later, in order to gather Five Blessingg experience, customers exchanged Five Blessingg by visiting other neighbors.

(3) Spring Festival blind box

Gifts with elements of the Year of the Rabbit, such as cups, red envelopes, scarves, ornaments, welcome cards, etc. Gifts are randomly combined, and the set value is controlled within 40 yuan.

3. Conduct an investigation group on primary ice.

(1) Snow Country Train Number

Sightseeing bus will be formed into a snow country train, and snow and ice elements will be properly decorated. Take tourists to visit the natural landscape of Baili in winter according to the route around the island. Choose the most representative locations as stops along the way, and arrange photographers to take photos for tourists free of charge. Departure time: 10:00-16:00 am, leaving on the hour.

(2) Walking briskly around the island

The activity is aimed at soliciting the participation of tourists who stay on the same day, and the scenic spot arranges special personnel to hold the team flag to lead the way. Enjoy the beautiful winter scenery of Baili in the morning along the way, and arrange photographers to take pictures for tourists free of charge. If no one signs up for the activity on that day, the activity will be cancelled and the train number will be changed to Xueguo. The time for marching into a group is 9:00 a.m.

4. Visit Dafudi Snow Field

(1) Ice and snow theme punching area (bubble carving)

Dafudi Snow Resort is an important display window of Baili’s winter tourism, and it is also the image card of Baili in the launching ceremony of the Cultural Tourism Hall. Setting up a unique photo punching device can effectively improve the functional attributes of the snow resort. The punching area is made of foam carving, which can be reused for a long time, including but not limited to subsequent ice and snow activities.

The punching area will be divided into three themes, ice and snow elements; Fireworks literature of youth (I Shijiazhuang); New Year elements in the Year of Rabbit.

5. Buy Baili Commercial Street

(1) Hometown Taste Characteristic Business Street

With Qingyin Pavilion as the center and peripheral merchants as the main body, we will carry out the hometown flavor market, and provide the full-featured products such as steamed buns, rice cakes, Gu Yue bean curd, preserved meat cauldrons, baked sweet potatoes, sugar-coated haws, etc. continuously, so as to arouse tourists’ long-lost flavor with the most familiar flavor.

(2) Baili local product market

The market consists of Xibaipo characteristic agricultural and sideline products, New Year gift boxes and Baili Baili commodities, which are displayed in the rest area on the north side of Qingyin Pavilion for tourists to buy.

6. Recreation ice sports

(1) Baijing Lake Ice Park

Make use of the lake space of Baijing Lake to build an iceberg paradise, and set up many ice fun projects, such as sledge-pulling, ice monkey-drawing, ice bowling, etc., to further enrich the park’s winter tourism projects and enhance the customer experience, which can be enjoyed by both parent-child families and urban youth.

(2) Snow Fireworks Party (night activities, attracting overnight stays)

Give priority to Dafu land, carry out night entertainment activities, punch cards and take pictures while fireworks pray. A large fireworks party is preferred, and in case of force majeure, it will be changed to holding cold fireworks.

■ Gulongshui Town

From January 1 to February 5, 2023, festivals with distinctive themes and various promotional activities were held, creating a travel experience integrating leisure, entertainment, shopping, culture and food for the people of the city.

1. Play while the iron is hot

Activity time: from grade one to grade six.

Venue: Xiaoxihu Lake in Guluan

2. Guluanshui Town Ice and Snow Festival

Guluanshui Town started the Guluanshui Town Ice and Snow Festival on January 1, and built a large-scale snow resort entertainment area in the block. Visitors can experience more than 30 kinds of entertainment facilities and experience the fun of the snow season.

3. Guluan New Year Festival

During the Spring Festival, Guluanshui Town will hold a large collection of new year’s goods, with hundreds of kinds of new year’s goods, to provide tourists with an annual shopping experience. Come here for shopping during the Spring Festival to satisfy everyone’s one-stop shopping experience.

4. Global Robot Carnival

Guluanshui Town introduced the Global Robot Carnival, which provided interesting robot performances and experiences for tourists during the New Year and brought more choices for the whole family to travel. You can watch nearly 100 kinds of robots at the scene, and you can also participate in interactive games, robot experience, and purchase robots.

5. Chinese New Year Drama Festival

Traditional drama and folk performances are the memories of the older generation, and Guluanshui Town will also launch the Chinese New Year Drama Festival, which will bring rich opera performances and musical instruments to send holiday blessings to middle-aged and elderly friends.

6. Happy New Year’s performances

The Spring Festival cultural performance is everyone’s favorite activity. This year, we have presented a number of wonderful Spring Festival performances to increase the fun of shopping. Fashion songs, ancient songs and dances, musical instrument solos, you can feel the joy of the festival when you stroll around Guluanshui Town.

7. China Spring Festival Garden Party in Guzhen

During the New Year, Guluanshui Town will also hold a variety of garden party activities to satisfy tourists’ multiple experiences of eating, drinking, traveling and shopping in the neighborhood. Hanfu Garden, Rabbit Spring Festival, Fun Games, Surprise Overlord Meal and many other experience activities are waiting for you.

8. Guluan Food City

In addition to the beautiful scenery and wonderful activities, delicious snacks have been prepared. On the eve of the Spring Festival, the neighborhood has been re-invested and planned, and hundreds of special foods are waiting for you to taste. At the same time, with the discount promotion activities of blocks and merchants, it will drive the local consumption boom.

9. Intangible Cultural Arts Festival

During the festival, Guluanshui Town will also hold an intangible cultural festival to inherit the artistic charm of intangible culture. At that time, provincial capitals and local inheritors of non-legacy technologies will be invited to give live exhibitions and performances, covering various skills such as sculpture, tanghua, clay figurine, hand-painted facial makeup, gourd pyrography and hand weaving.

■ Jinzhou New Century Shopping Mall Pedestrian Street

Activity content: the first "New Year Collection" in Jinzhou City

China’s intangible cultural heritage China tanghua, Shijiazhuang municipal intangible cultural heritage Liu Hulu pyrography, Jinzhou intangible cultural heritage antique doll, New Year’s goods, Spring Festival couplets, lanterns, melon seeds and candy.

■ Zanhuangtang Street

Activity content:

1. On January 14th-15th, 2023, the first Tang costume photography exhibition was held in Tang Street. During the event, Tang costumes were performed, and non-legacy folk culture exhibitions were held, such as Sugar Man, tanghua, folk paper-cutting, artistic sculpture, artistic calligraphy and painting, palace lantern exhibitions, etc.

2. From January 1 to January 31, 2023, Tangjie Recreation Carnival covers large-scale wonderful and diverse amusement projects such as Need for Speed, Time Plane, Carousel, Dream Pirate Boat, etc.

■ Jingxing Ceramic Water Town

Series of activities of "Jingxing —— Spring Festival Temple Fair in Ceramic Water Town"

First, the activity time:

January 14th to February 5th, 2023

Second, the activity content:

1. Theme 1: Ceramic Water Town New Year Collection

At the turn of the old and the new approaching the end of the year, there is a traditional custom of buying new year’s goods in China. By buying new year’s goods in Ceramic Water Town, local residents create an annual market belonging to Jingxing Ceramic Water Town, which sets off the atmosphere of the New Year.

Activity time: January 14th, 2023-January 21st, 2023.

Venue: East Parking Lot of Ceramic Shuidong

Theme: 2023 "New Year Festival" in Ceramic Water Town

Activity time: January 14th, 2023-January 21st, 2023.

Theme of the event: 2023 Spring Festival couplets in ceramic water town love Wanjia.

Activity time: January 14, 2023

2. Theme 2: Ceramic Water Town Spring Festival Temple Fair

From the memory of catching a big episode, to watching the lion dance churning and frolicking in the joyful gongs and drums, and then going shopping in the garden to eat candied melons, the traditional culture of China is once again written into the window of blessing. After three years of epidemic, the tourism industry has been fully liberalized this year, which is also a signal that the tourism industry is in a favorable situation, and the lives of ordinary people will gradually get on the right track. With the progress of modern society and the development of the times, the very important folk custom of the Spring Festival is facing an intangible crisis, that is, it is getting less and less stale in the traditional sense. In order to create a new year atmosphere, Ceramic Water Town will dig deep into the annual flavor of the traditional Spring Festival in 2023 and combine the needs of modern individuality and diversification to create an annual flavor Jingxing series belonging to the ceramic water town.

Activity time: January 22, 2023-February 5, 2023

Venue: Ceramic Water Town Cultural Street and Ancient Village

3. Theme 3: Prosperous China is intoxicated with the new era.

Activity time:

January 22nd, 2023-January 26th, 2023

February 4, 2023-February 8, 2023

Activity overview:

Convene performance teams from surrounding villages and towns to integrate performance programs, and divide folk performances such as folk performances, non-legacy cultures, fireworks shows, lanterns, dozens of traditional snacks, traditional performances, banban operas, amusement facilities, social fires, dragon and lion dances and so on into regions, so as to create the atmosphere of the New Year Temple Fair in the 1990s and return the Spring Festival to the traditional flavor.

Activity rules (visitors):

Visitors can get a lucky bag in the tourist center after collecting 8 lucky cards, and get a free prize when they get a lucky bag. They can also pay attention to WeChat official account, a ceramic water town, and the video number to get a string of lanterns for free.

■ Jichao Commercial and Cultural Pedestrian Street in Wuji County

First, the theme of the event: the climax of the New Year.

2. Venue: Jichao Commercial and Cultural Pedestrian Street, Wuji County

III. Activity Time: December 23, 2022-February 6, 2023

IV. Activities:

1. Extreme Spring Festival

From January 5, 2022 to January 20, 2023, a quality New Year’s Fair will be held in the neighborhood to fully meet the needs of residents for the New Year:

Traditional intangible heritage: machine embroidery, tanghua, paper-cutting, calligraphy, painting and calligraphy, hand-painting, gourd pyrography, leather art, copper wire handwork, etc.

Special snacks: hot milk fort, strawberry tower, fried dough sticks wrapped in sesame paste, spaghetti, spicy fried rice cake, hot red wine, mouth-mixed wine, rock sugar baked pear, traditional cakes (Osmanthus Jelly, Gordon Euryale cake, striped cake), baked sugarcane, cotton candy, red bean cake, rice cake, dried fruit, candied fruit, etc.

Festive decorations: snuff, window grilles, lanterns, Spring Festival couplets, stickers, balloons, clothes rented by fairy wand and online celebrity (Hanfu, horse-faced skirts), luminous headdresses, etc., which fully highlight the festive atmosphere;

Wonderful interlude: during the event, a food festival will be organized, so that the vast number of merchants will take to the streets to let consumers enjoy it. At the same time, cultural performances and interactive activities such as New Year’s blessing and punching cards, Golden Lion’s New Year greeting and Muppets’ interaction will be designed to provide tourists with an annual shopping experience.

Promotion and promotion: the block combines with the residents’ preferential coupons to carry out vigorous publicity, and at the same time withdraws from a series of activities, such as the block consumption lottery, the courtesy of punching cards on the wall, the preferential activities of block merchants, and the courtesy of consumption cards, to fully stimulate consumption.

2. Lantern Festival

From February 3 to February 6, 2023, the Lantern Festival was organized, and solve riddles on the lanterns, lion dance, non-legacy performances and performances were held to create a festive atmosphere and let the people feel the rich Chinese excellent traditional culture.

■ yuanshi county Banquet

I. Activity Time: January 1-February 15, 2023

2. Venue: yuanshi county Night Banquet Characteristic Commercial Street+Hanfeng Market.

Third, the theme of the event: New Year Festival+New Year Collection+Ice and Snow Carnival

Create the first choice festival for citizens to buy new year’s goods with rich flavor, excellent quality and close price. In Tik Tok, Aauto Quicker and other all-media channels, hot topics such as "the taste of the year in memory" were launched, which aroused the participation and discussion of netizens, created an all-round atmosphere to attract the surrounding people’s shopping and consumption activities, and really detonated the "yuanshi county New Year Festival".

IV. Activities:

1. New Year Festival

By displaying the famous and special products in Yuanshi County, holding special product promotion meetings, live broadcast activities and cultural performances, this activity will create an all-round atmosphere to attract the people around Shijiazhuang to shop and consume, prosper the consumer market in yuanshi county, promote the economic growth of agricultural and sideline industries, and stimulate the overall consumption of the county, making it a win-win event for both economic and social benefits.

2. New Year Collection

Fireworks return, warm the Chinese New Year, expand the local product market, push characteristic products to a wider market, further expand domestic demand to promote consumption, and help to resume work and production and rural revitalization. While enriching everyone’s dining table, it also enriches entertainment life, makes the taste of the year more "fragrant", exhausts the "net" of the taste of the year and brings "Ji" home!

3. Ice and Snow Carnival

The ice and snow tourism market will usher in the peak consumption season during the Spring Festival. People will experience the ice and snow carnival in addition to visiting relatives and friends and greeting each other. This ice and snow carnival is the first outdoor ice and snow entertainment project in Yuanshi County. It mainly includes skiing circle experience, snow off-road vehicles and other recreational projects, as well as a series of delicious food and special snacks, so that visitors can feel the charm of ice and snow in the characteristic commercial street of yuanshi county Night Banquet.

4. Promote profits

The Development and Reform Commission of Yuanshi County provided 200,000 yuan as consumption vouchers for the smooth progress of this activity, which were used in a matching way according to the ratio of 1:4. The actual consumption amount was 4 times or more of the consumption vouchers, and only one consumption voucher could be written off for each consumption, and the consumption vouchers could be superimposed on the basis of merchants’ preferential treatment.

■ Yingpan Commercial Street in Xingtang County

1. Yingpan Food Festival. At that time, special snacks from all over the country, including local and exotic foods, will be gathered through the food festival stage to gather popularity and promote consumption.

2. New Year’s Collection. The Spring Festival is a traditional festival of the Chinese nation. According to the Chinese people’s traditional habits of Spring Festival couplets, a special Spring Festival with the theme of "Spring Festival" is created.

3. Yingpan Commercial Street Light Show. Taking lighting technology and culture as the main line, and a large number of neon lights as the main venue atmosphere, the rainbow staircase of online celebrity lighting is formed, and various beautiful lighting shows are set up to bring a rich visual feast through bright lighting shapes.

4. Yingpan Ice and Snow Carnival. Taking advantage of the Spring Festival peak season, with the theme of "Happy Ice and Snow Tour", the only project in winter every year attracts attention.

The block will create a high-quality consumption environment, enrich people’s lives through colorful activities, further promote local consumer confidence, enhance urban economic development, and contribute to the sound development of the city’s economy.

■ Gaocheng Miyagi Yinxiang (Gongli Street)

Gaocheng Guo Chao nian Wei temple fair

I. Activity time: from January 14th to February 5th, 2023.

2. Business hours: 9:00-22:00

3. Venue: Wangyang Commercial Plaza+Gongli Street

IV. Activities:

The content of the activity is divided into two parts as a whole. First, catch up with the big episode in the twelfth lunar month; Second: visit the temple fair in the first month; Around the content of two large plates, the time span is 30 days; Years ago, you can buy new year’s goods here and feel the atmosphere of the market. The products cover: grain and oil, non-staple food, dry goods, fruits, clothing, seafood, decorations for the Spring Festival atmosphere and so on.

Years later, the scene-based multi-block temple fair mode was launched, with Chaowan block, folk-custom block, New Year’s Day collection, cultural block and gourmet block, and the five blocks started the Spring Festival Zhou Bianyou crazy hi mode, which is definitely an excellent place for Gaocheng, whether for strolling around the baby or traveling around!

1. New Year Collection

A collection of new year’s goods full of annual flavor, regional characteristics and the most grounded atmosphere, bringing together all kinds of new year’s goods, so that the people in the city can also find the old fireworks. The time span is from the fifteenth to the thirtieth of the twelfth lunar month. The investment promotion format covers all the formats of Spring Festival New Year’s goods, as well as local agricultural and sideline products in Gaocheng, especially township products!

2. Folk blocks

(1) He Xinchun, the Five-way God of Wealth: In different time periods, the Five-way God of Wealth walked into the block and took photos with tourists to enliven the atmosphere of the block, so that tourists could welcome the Spring Festival and win a good prize.

(2) Non-legacy folk programs: Miyagi drums, northern Zhou hexagrams playing randomly, folk folk performances: dragon and lion dancing, boating, walking on stilts, etc … organized and planned non-legacy performances during the first month.

(3) Folklore souvenirs+regional agricultural and sideline products: folk cultural souvenirs such as straw animals, dough sculptures, sugar blowers, gourd pyrography, candied haws, etc., combined with Gaocheng related associations to graft folk intangible items.

(4) Folk acrobatics: Dinggang, flying saucer … all kinds of folk acrobatics, enriching the vision of the neighborhood and driving the atmosphere of tourists.

3. Chaowan block

(1) Punching in the snow in the block: In the central square of Gongli Street, create a 600-square real snow scene, with two dedications every day. In the winter of Gongli Street, you can experience the romance of bald heads every day!

(2) Children’s play interaction: divide special venues, equip with conventional and customized children’s play equipment and interactive DIY activities.

(3) Transformers interactive performance: A live-action version of Transformers will be staged at the event, and the cool-looking Transformers mecha will definitely attract children’s attention and become the focus of the audience.

4. Food block

(1) Taste of the Year Taste Buds: Integrate Gaocheng regional specialty food and online celebrity specialty snacks, and eat them nonstop from the year before to the year after!

(2) The taste of the year and the taste of the tide: integrating online celebrity’s special snacks-smoking ice cream, brothers throwing bowls of wine, Changsha stinky tofu, Sichuan hot and sour powder and so on.

5. Cultural blocks

Famous for the three palaces: Palace culture is a loud and powerful business card in Gaocheng, where you can enjoy palace wine, enjoy palace lanterns and eat palace noodles. At that time, more people around Gaocheng can be radiated during the activities, so that more people can know about the three palaces culture in Gaocheng!

■ jingxing mining area Taigu Qingxi Characteristic Commercial Street

I. Activity Time: February 4, 2023-February 9, 2023

2. Venue: Jiazhuang Ancient Town, jingxing mining area

Iii. Activities:

1. Folk performances. In the New Year’s festival, colorful folk performances are presented, and with the help of festival traditions, folk cultural performances are integrated into the neighborhood, such as drums, sedan chairs, old ladies sending their daughters away, non-legacy social fires, and non-legacy flower-pulling performances, creating a strong Spring Festival atmosphere and making consumers feel a strong sense of the year.

2. Traditional snacks and food exhibition. On-the-spot production and display of traditional food with mining characteristics in the neighborhood, such as handmade vermicelli, Fengjiagou sip beard, cold rice noodles in the mining area, Qingquan rice cake, grilled cake, etc., will promote the traditional food culture and attract consumers to taste it.

3. punch in the children’s garden. Organize children’s favorite activities, such as treasure hunting on the beach in Shachi Garden, bottle feeding fish, DIY hand painting, educational area, etc.

4. solve riddles on the lanterns, online celebrity Lighting District. Solve riddles on the lanterns activities are set up in the lighting area, and riddles are set up in the lighting areas such as dynamic light tunnel, Ferris wheel, Angel’s wing, Dragon and Phoenix Chengxiang, Zodiac, online celebrity Bear, etc., so that customers can enjoy the light show and get involved in the riddles of the traditional Lantern Festival and feel the festive atmosphere.

5. Visit temple fairs. Merchants in the block combine consumption activities with temple fairs to achieve the festive atmosphere of temple fairs shopping, so that everyone can recall the atmosphere of their childhood visits to temple fairs, and provide Hanfu photography, sugar blowers, calligraphy and painting, candied haws, etc., to enrich the shopping experience and celebrate the New Year.

■ Xinle Fuxi South Lane Totem Impression Commercial Street

1. Activity content: New Year Temple Fair in Xinle City, New Year’s Collection.

Second, the activity time: January 14th to February 5th.

With the theme of "New Rhyme Temple in the Ancient City is full of fun", this new year’s festival collection gathers large-scale entertainment, non-legacy exhibitions, cultural performances, national wind cruises, special new year’s products, festival supplies exhibitions and other colorful theme activities, creating a new year’s feast with all forms of integration, bringing full affection to Xinle citizens for the new year’s new year’s goods and a lively atmosphere for the new year. (Reporter Jiao Lili)

　　On May 30th, Chongqing Municipal Bureau of Planning and Natural Resources and Chongqing Meteorological Bureau jointly issued the meteorological risk warning of geological disasters in Chongqing.

　　From 20: 00 on May 30 to 20: 00 on May 31, Chengkou County, Kaizhou District, Wuxi County and fengjie county belong to high-risk areas, and the meteorological risk level of geological disasters is Grade III (yellow warning), Yunyang County, Wanzhou District, Zhongxian County, Liangping District, Dianjiang County, Changshou District, jiangjin district, Qijiang District, Fuling District, Fengdu County and Shizhu County.

　　Heavy rain occurred in 5 districts and counties, and 15 small and medium-sized rivers experienced the process of rising water.

　　According to the monitoring of Chongqing Hydrological Monitoring Station, from 8: 00 on the 30th to 8: 00 on the 31st, there were heavy rains in five districts and counties in Chongqing, including Banan, Jiangjin, Changshou, Fengdu and Xiushan, among which there were heavy rains in Fengdu and moderate rains in other areas. The maximum daily rainfall occurred in Fengyu and Wuyang Village, Longxiang Township, which was 100.5mm.. Affected by rainfall and upstream water, 15 small and medium-sized rivers, such as Longtan River in Fuling District and Meixi River in fengjie county, experienced a 1-4 meter flood process, and the highest water level did not exceed the warning water level.

　　(Headquarters reporter Chen Peng, Wang Hongchao, Fa Qi)

originate

Not long ago, the National Health and Wellness Commission and other six departments jointly formulated the "Second Batch of Rare Diseases Catalogue", which newly included 86 rare diseases. Together with the first batch of 121 rare diseases included in 2018, at present, there are 207 rare diseases included in the catalogue in China.

In recent years, the word "rare disease" has appeared more and more frequently in everyone’s field of vision. For example, in the news, the father developed "self-made medicine" for his son’s complex disease, and then in the past two years, the price negotiation of medical insurance was hot, and most of them were related to rare disease drugs.

The "drug god father", who was known on the Internet in 2021, took his son to be injected with gene therapy drugs in June 2022, and was also the first patient with Menkes disease who underwent gene therapy in China | See the watermark for the source.

In the past two years, the medical insurance price negotiations have always been hot headlines, and drugs related to rare diseases are included in the national medical insurance drug list every year | Source: CCTV News

Therefore, many people have the impression that the concept of rare diseases is both familiar and unfamiliar: rare diseases don’t seem so "rare", it seems difficult to treat them, and there don’t seem to be so many experts studying rare diseases …

But these superficial impressions are not enough to describe the whole picture of rare diseases.

What is a rare disease? Really "rare"?

In fact, different countries have different definitions of rare diseases. For example, the United States generally defines it as a disease with fewer than 200,000 people in China (that is, about 1 in 1,500), while the prevalence rate in Europe is less than 1 in 2,000.

According to China’s "Research Report on the Definition of Rare Diseases in China 2021", the definition of rare diseases in China is: "Diseases with neonatal morbidity less than 1/ 10,000, morbidity less than 1/ 10,000, and patients less than 140,000 are classified as rare diseases". The main reason is that China has a large population base. If the definition is too loose, the pressure on drug research and development and medical insurance will be too great.

Taking Europe as an example, different countries have different definitions of rare diseases, which often need to be considered according to factors such as population, drug research and development (the unit is every 100,000 people) | Source: Chung C C Y, et al. 2022.

You may be curious: since the prevalence rate is one thousandth or one thousandth, why do you say that it may be too loose to put pressure on the medical system? That’s because the concept of rare diseases is actually a collection of thousands of diseases, or collectively.

According to incomplete statistics, the number of known rare diseases is about 6000-8000. Although the prevalence rate is not all 1/2000, this figure is still very scary-according to the statistical estimation of the incidence rate of 3585 rare diseases, there are about 263-446 million people suffering from various rare diseases all over the world.

This is why, although it is called a rare disease, this group is not "rare" at all.

What does it mean to have a rare disease?

What does it mean to get this rare disease with a probability of one thousandth? Will it become a rare object that is taken care of by everyone like the stars holding the moon?

At least at present, most patients with rare diseases are not so lucky.

First of all, you have to diagnose what disease you are.

But in fact, the diagnosis of rare diseases is very difficult because of limited medical resources and imperfect medical knowledge. About half of the patients with rare diseases in the world still don’t know what disease they have, and the remaining half still face problems such as delayed diagnosis, wrong diagnosis, no treatment plan and unattended care.

What does this mean? If there is a rare patient in Europe, Xiao A, who suddenly has an attack, there is a 25% possibility that Xiao A will not know what disease he has until five years later. In 40% cases, different doctors will give Xiao A different diagnosis and different treatment schemes, and most of these treatment schemes are not helpful to Xiao A because of misdiagnosis.

However, under this wave of operation, Xiao A may have spent a lot of money to cure the disease.

"Layer-by-layer Screening" of Rare Diseases in Europe from Diagnosis to Treatment

In China, however, the shortage of medical resources will only make these ratios higher.

Suppose Xiao A was lucky enough to get an accurate diagnosis in just one year. At this time, the doctor turned over a long list of rare diseases and told Xiao A with regret that there was no medicine for your disease. Because now more than 90% of rare diseases have no good treatment.

This is also the reason why it was mentioned at the beginning that two years ago, the father could only develop drugs to treat his son himself.

As a result, Xiao A will fall into long-term hospitalization or drug treatment, not only can barely maintain his life, but also bear the sky-high medical expenses for life-for example, patients with cystic fibrosis need about 280-1.9 million euros in medical expenses for a lifetime.

Let’s assume that Xiao A is super lucky. Not only is he diagnosed quickly, but he also finds that this rare disease has a very effective orphan drug (rare disease is also called "orphan disease" because the patient is rare, just like "orphan"). As a result, ta may be shocked when he looks at the drug price: it is reported that the average price of rare disease drugs used by each patient is 4.8 times that of other diseases.

You can do a "simple math problem": in 2014, the development of a new drug in China will cost about $1.2 billion, and to maintain the research and development of the whole pharmaceutical industry, it is required that the sales volume should be at least $15 billion. According to the maximum subsidy of 300,000 RMB (about 50,000 US dollars) provided by medical insurance, at least 300,000 patients are needed-and a rare disease is defined as a disease with less than 140,000 patients. Then it requires higher pricing, so that drug researchers and the whole industry can "return to the original".

In other words, patients with rare diseases have to pay more for treatment than other patients.

What does it mean to study rare diseases?

But why are drugs for rare diseases so expensive? Are biomedical companies all black-hearted enterprises? In fact, it is not only patients, but also researchers of rare diseases.

However, the research on rare diseases in China is on the rise, even catching up with common diseases. The above figure shows the number of published research articles, and the following figure shows the number of clinical trials | Source: Yang L, et al.2015.

Suppose researcher Xiao B wants to study a rare disease. The first question Xiao B faces is: Where is my research object?

Although the definition of rare diseases is less than 140,000 people, it sounds like a large number, but in fact only a small number of patients will go to the hospital, and they are scattered in hospitals all over the country.

Not to mention finding a needle in a haystack, it should be as difficult as finding a needle in a swimming pool.

Let’s continue to assume that Xiao B is lucky enough to collect information about dozens of patients with rare diseases in several hospitals and prepare for research. At this time, the question comes again-where does the research funding come from? Rare diseases are mostly genetic diseases, and the study of rare diseases requires gene sequencing, data analysis, animal experiments and so on, which require no less funds than ordinary diseases.

However, from the simple relationship between supply and demand, patients with more common diseases often get more financial support; However, there are more than 5,000 rare diseases with different pathogenesis, so much research funds are available, and what researchers can get is often a drop in the bucket.

From diagnosis to research and development of rare diseases, every step is money, especially when ordinary sequencing (exon sequencing, ES) is ineffective, it is more complicated for researchers to judge the difficulty and exploration direction of rare diseases | Source: Marwaha S, et al. 2022.

However, assuming that Xiao B is lucky, he just applied to the National Natural Science Foundation of China, which has started to increase funding for research on rare diseases in recent years, and got a lot of research funds. Xiao B intends to do a big job to develop an effective drug for this rare disease and solve this rare disease once and for all!

So Xiao B collected patient information, sequenced to find rare disease targets, and began to screen different drugs;

After discovering hundreds of drugs that may be useful, carry out cell experiments and animal experiments;

Finally, five drugs may be effective, so they went to clinical trials;

After the first phase, the second phase and the third phase of the clinic, I was particularly lucky that a drug was proved to be effective;

Start the long drug approval and enter the fourth phase of clinical practice;

Finally, the drug was put into use.

So more than ten years have passed.

Process of new drug research and development | Source: Shanghai Institute of Pharmacology, China Academy of Sciences

In addition, the results brought by the small sample size of patients are unreliable, the experimental design is difficult, and the treatment is not necessarily extensive and effective, which are puzzling the researchers of rare diseases.

It can be seen that it is a thankless thing for researchers to study rare diseases and develop related new drugs.

We can’t ignore it just because it’s "rare"

However, we can’t ignore hundreds of millions of patients with rare diseases because rare diseases are rare, or because research is "thankless".

For patients, governments all over the world have gradually realized the importance of rare diseases, and have increased investment in relevant medical insurance policies, so that more and more patients can get the best treatment at acceptable prices. There was also a hot search for high-priced drug negotiations in the previous two years.

By the end of this year, more than 50 kinds of 75 kinds of drugs for rare diseases that have been approved for listing in China have been included in the medical insurance drug list.

The status quo of rare disease drugs included in medical insurance | Source: Comprehensive report on rare diseases

For the drug research of rare diseases, different countries often support the development of rare diseases drugs from the aspects of research and development funds, drug approval cycle, drug tax relief and so on. In recent years, China has also improved the laws and regulations in this area to better support the research of rare diseases in China.

From the end of last century, governments and research institutions in various countries gradually realized that rare diseases are not rare, and they also deserve public attention. From diagnosis to treatment, from research to drugs, there are more and more different supports, but in the face of 300 million patients and thousands of diseases, the progress now is far from enough.

As a trivial biological science popularization person, we also hope to make a contribution in this respect. Now that China has listed 207 rare diseases, we will try to introduce these "orphan diseases" in simple and easy-to-understand language, which you may have never heard of.

I believe that as long as everyone knows something, orphan disease will no longer be lonely.

References:

? Chung C C Y, Hong Kong Genome Project, Chu A T W, et al. Rare disease emerging as a global public health priority[J]. Frontiers in public health, 2022, 10: 1028545.

The Third Multidisciplinary Expert Seminar on the Definition of Rare Diseases/Orphans in China, Research Report on the Definition of Rare Diseases in China 2021.

Comprehensive report on lilac orchard and rare diseases

? Ferreira C R. The burden of rare diseases[J]. American journal of medical genetics Part A, 2019, 179(6): 885-892.

? Yang L, Su C, Lee A M, et al. Focusing on rare diseases in China: are we there yet? [J]. Orphanet journal of rare diseases, 2015, 10(1): 1-2.

? Griggs R C, Batshaw M, Dunkle M, et al. Clinical research for rare disease: opportunities, challenges, and solutions[J]. Molecular genetics and metabolism, 2009, 96(1): 20-26.

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