Orphan drugs and medical devices are related to the forefront of science and technology, with high R&D difficulties, long cycles, and high costs. However, the market size is relatively small. It is difficult to effectively motivate enterprises to increase R&D investment through market mechanisms alone. How to improve product accessibility and help patients share the dividends of reform and development is an important issue during the process of Chinese modernization. The United States, the European Union, Japan, Taiwan province of China, and other countries and regions have formed useful experience in solving product supply problems through legislation, especially specialized legislation. With the improvement of economic strength, scientific and technological strength, and comprehensive national strength, it has become a consensus among all sectors of society to draw on the experience of comparative law to carry out specialized legislation at the national level. As the country's rare disease prevention, treatment and protection work enters a new stage of high-quality development, the Law on Promoting the Development of orphan drugs and medical devices should be formulated and promulgated as soon as possible. This law belongs to promotional legislation, with empowerment, incentive and support as the main approach of adjustment. On the basis of defining basic concepts, such as rare diseases, it concretizes existing incentive policies and localizes comparative legal experience. It creatively sets up incentive systems, such as product qualification recognition, market exclusivity, and tax reductions. On the track of the rule of law, institutional innovation and institutional synergy are used to enhance product accessibility and promote people's health and well-being.

Objective: To sort out the policies related to rare disease drugs in China, exploring their incentive and promotion effects on the marketed entry of rare disease drugs. Additionally, the implementation effects and shortcomings of the policies were analyzed, and suggestions to improve the policy of rare disease drugs were put forward. Methods: China's policies on R&D registration and medical security of rare disease drugs and approved rare disease drugs from 2018 to 2024 were summarized and analyzed. Results: China's rare disease drug policies currently focus on the research and registration of drugs prior to market approval, as well as the construction of post-market medical security systems. Under the impetus of policies, the difficulties on research and development of domestic rare disease drug in China has decreased, the time to market has been shortened. Also, the number of drugs in the pipeline and those already in the market has continued to grow. While ensuring the accessibility of rare disease drugs for patients, medical security policies have also significantly reduced the financial burden on patients. Flexible clinical research and development strategies have accelerated the domestic market entry of foreign rare disease drugs, and most domestic research and development pipelines have also accelerated their progress under the guidance and effective combination of multiple policies. Conclusion： In the future, China should accelerate the formulation of guiding documents and continuously improve the establishment of comprehensive policy system and management mechanism for rare diseases. This will encourage domestic pharmaceutical enterprises in China to enhance their independent innovation and R&D investment, and support the research and development and market entry of innovative and generic drugs for rare diseases, so as to accelerate the development of China's rare disease industry.

Human genetic resources are an important strategic resources for the development of science and technology. The scientific research on human genes not only holds significant potentials for development and utilization value but also poses biological safety risks. In order to implement the “Regulations of the People's Republic of China on the Management of Human Genetic Resources” (hereinafter referred to as “the Regulations”), further improve the standardization level of human genetic resources management in China, strengthen the management of human genetic resources, and promote the effective protection and rational use of human genetic resources, the Ministry of Science and Technology of the People's Republic of China (hereinafter referred to as “Ministry of Science and Technology”) issued the “Implementing Rules of the Regulations on the Management of Human Genetic Resources” (hereinafter referred to as the “Implementation Rules”) and has successively released several notifications regarding the administrative approval management of human genetic resources, and adjusted relevant approval processes. How to optimize the supervision and application process of clinical trials and scientific research projects on the basis of standardized management has become an extremely important issue to hospital management. This article is set against the backdrop of “the Regulations” and the “Implementation Rules”. It summarizes, based on the characteristics of the review process at various stages of actual application, the management mechanisms for human genetic resources, related system construction, and declaration situation at the Dermatology Hospital of Chinese Academy of Medical Sciences over the past four years. Focusing on several aspects of human genetic resources collection, preservation, international cooperation in scientific research, and the provision or open use of information to the outside world, the paper summarizes the main problems found in the process of project declaration and puts forward targeted improvement measures in order to promote the standardized management of clinical research, in order to provide reference suggestions for medical institutions in strengthening human genetic resources management.

Proteasomes are widely distributed in cells and play important a regulatory role in most cell biological pathways to maintain protein homeostasis. They can be further divided into constitutive and immune types. Abnormalities in its function have been found to be closely related to the development and progression of tumors, infectious diseases, neurodegenerative diseases, and autoimmune diseases. Currently marketed drugs are mainly pan-proteasome inhibitors, and some immune-based proteasome inhibitors are under development. This article provides a review of the structure and function of the proteasome, its physiopathologic roles, and the current status of drug discovery and development against proteasomes, which will bring new thoughts and insights into the study of the proteasome and the development of targeted drugs.

It is vital to protect the safety, rights, and interests of subjects in clinical trials. Ethical review of the completion or termination of clinical trials is an important measure to protect the human subjects who volunteer for these trials. Ethics committee give approvals to the completion or termination of the trials and might agree after necessary modifications and list the suggestions when the project needs further processing. Based on the actual work conditions of  ethics committees, the authors analyzed and discussed the current problems of completion and termination of clinical trials, especially the reasons for terminations, the harm of forced terminations, and the key points of ethical review to propose reasonable countermeasures and provide specific suggestions for the ethical review after the completion of clinical trials.

The objective of accelerating postoperative recovery is to enhance the quality of recovery and improve patient satisfaction. The recovery quality scale is a patient-centered outcome that comprehensively assesses patients' postoperative  health status and serves as a recommended indicator. Recent studies have shown that low-dose or sub-anesthetic dose of esketamine as an adjunct to general anesthesia can reduce pain intensity and opioid requirement, decrease postoperative hyperalgesia, and prevent postpartum depression. This article reviews the research progress of the effects of esketamine, when used as part of a multimodal analgesic regimen, on the quality of recovery of adult patients undergoing different types of surgery.

The endometrium is an important part of the female reproductive system, characterized by a variety of physiological functions and complex structures. At present, due to the lack of research models to characterize the genesis and developmental characteristics of the endometrium, the research on the mechanism of endometrial diseases and the development of therapeutic drugs is limited. Organoids are self-assembled three-dimensional cellular structures that retain many physiologically relevant and functional features of their native tissue. The genetic, histological, and biological characteristics of endometrial organoids are consistent with those of the original tissues and organs. These organoids not only respond to exogenous hormones, thereby  reproducing the physiological cycle of endometrium in vitro, but also simulate the complex process of blastocyst implantation. This article reviews the application and prospect of endometrial organoids in physiological fertility, disease research, and clinical translation.

l of Pharmacy, Hainan Medical University, Haikou 570300, China)
［Abstract］　Objective: Agarwood has been widely used in incense since ancient times. It has the effect of sedation and tranquilization. Modern pharmacological studies have shown that agarwood has a good sleep-promoting effect, and its active components are mainly sesquiterpene compounds. But the mechanism of action has not been explained. In this study, molecular docking technology was used to verify the mechanism of action and the possible drug targets of agarwood sesquiterpene compounds for insomnia prevention and treatment. Methods: Agarwood sesquiterpenoids, key targets of insomnia prevention and treatment, as well as their structural formulas, were obtained through the database, and the chemical components and their targets were verified by molecular docking using AutoDock software. Results: A total of 186 agarwood sesquiterpene compounds were collected and scored by interlinking with key targets through molecular docking. The threshold value of affinity ≤-5 kcal·mol^－1 was generally selected. The lower the score is, the higher affinity between ligand and receptor was obtained, which was considered as potential affinity. The conformation with the lowest affinity was used as the best docking conformation and visualized. Molecular docking found that five of the 186 compounds were highly bound to eight selected key targets. The neuroprotective activity of five compounds (G32, G39, G40, G41, M18) was screened in vitro with the IC₅₀ of (6.22±0.35), (5.72±0.22), (4.37±0.56), (4.03±0.26), and (3.05±0.13) μmol·L^－1, respectively. The IC₅₀ value of the positive drug diazepam was 3.12 μmol·L^－1, and the neuroprotective effect of compound M18 was slightly greater than that of positive drug. Conclusion: The study showed that some reported agarwood sesquiterpene compounds could be highly combined with insomnia related targets, which provides scientific data and reference for the study of molecular mechanism and pharmacoactive substances of agarwood for the prevention and treatment of insomnia.

Objective: To explore the effects of different material compositions (formula) of Massa Medicata Fermentata (MMF) on intestinal flora and gastrointestinal hormones in mice with spleen deficiency constipation based on the network pharmacology. Methods: Using network pharmacology to predict the potential function of Massa Medicata Fermentata-constipation, the model with spleen deficiency constipation was established in mice. In the modeling phase, the MC group was gavaged with sterile water, while the model group was gavaged with folium sennae decoction for 7 d, and then the diet and drinking water were restricted for 8 d. After successful modeling, the mice in the model group were randomly divided into four groups: model (MM) group, Massa Medicata Fermentata 1 (MS1) group, Massa Medicata Fermentata 2 (MS2) group, and Massa Medicata Fermentata 3 (MS3) group. MC and MM groups were given sterile water, and mice in MS1, MS2, and MS3 groups were given Massa Medicata Fermentata S1, S2, and S3, respectively, for 7 d. After the intervention, blood samples and intestinal mucosa samples of mice in each group were collected for gastrointestinal hormone motilin (MTL) and gastrin (GAS) level determination and 16S rRNA high-throughput sequencing. Results: Network pharmacology showed that the signal pathway of medicated leaven in treating constipation involves gastric acid secretion and neuroactive ligand-receptor interaction. The weight change rate of mice with spleen deficiency constipation decreased significantly, and that of mice after intervention of MMF with different material compositions increased significantly compared with the normal group. And compared with model group, the weight change rate increased at the same time. Massa Medicata Fermentata with different material composition can improve the moisture feces content of mice with spleen deficiency constipation into more normal levels. The analysis of gastrointestinal hormone levels showed that the levels of MTL in mice with spleen deficiency constipation decreased significantly. After intervention with different material compositions of MMF, the levels of GAS in each intervention group had no significant difference, and the levels of MTL in MS2 and MS3 groups increased significantly. Sequencing analysis indicated that the intervention of MMF with different material compositions could effectively restore the composition structure of intestinal mucosal flora in mice with spleen deficiency constipation. LEfSe analysis showed that, compared with MM group, the intervention of MMF with different material compositions could reduce the abundances of Bifidobacterium, Faecalibaculum, Coriobacteriaceae_UCG_002. The intervention of MMF S1 and S3 can significantly increase the abundance of Lachnospiraceae_UCG_001, while the intervention of MMF S2 and S3 can significantly increase the abundances of Psychrobacter and Atopostipes, and decrease the abundance of Streptococcus. Correlation analysis showed that Mucispirillum in MS1 group, Psychobacter and Paenalcaligenes in MS2 group, and Psychobacter in MS3 group were positively correlated with MTL. Conclusion: MMF with different material compositions can regulate the levels of MTL, restore the structure of intestinal mucosal flora in mice with spleen deficiency constipation, and regulate the abundance of dominant intestinal bacteria. Bifidobacterium, Faecalibaculum, Psychrobacter could be the key bacteria to identify the intervention of MMF with different material compositions in mice with spleen deficiency constipation. MMF may improve spleen deficiency constipation by regulating the abundance of Psychrobacter bacteria and increasing the level of MTL.

Objective: To establish a method for determining the aerodynamic particle size distribution (APSD) of revefenacin inhalation solution and to provide a reference for subsequent quality studies on this generic drug. Methods: The APSD of revefenacin inhalation solution was determined by the next generation impactor method. The aerosol content was determined by HPLC, and the in vitro nebulization characteristics of revefenacin inhalation solution was evaluated by fine particle dose, fine particle fraction, mass median aerodynamic diameter and geometric standard deviation. Results: The method has good precision and robustness, and the loss rate at different stages was negligible. The nebulization can be completed in 10 min. There was no significant difference in the determination results in the range of flow rate 15 L·min^－1(±5%). The results also showed no significant variation under the test conditions （20~25 ℃、35% RH~55% RH）. There are differences in the results of the APSD measurements obtained by using three compression nebulizers of different brands and models. The PARI BOY nebulizer is suitable for the APSD measurement of this variety. Conclusion: This study established a method for determining the APSD of revefenacin inhalation solution, which was validated. An appropriate nebulizer was also identified. These findings can provide a basis for future quality research of this drug, and offer a reference for developing nebulization characteristics of inhalation solutions in vitro.

Objective: To study the pharmacokinetics of crisaborole ointment in healthy subjects in China, and to evaluate the bioequivalence between the domestic test preparation and the original reference preparation. Methods: A single dose, randomized, open, two-period, crossover drug trial design was adopted. A total of 36 healthy subjects were randomly divided into two groups, and administered test preparation T or the reference preparation R (crisaborole ointment, 4.0 g) each period, respectively. The concentrations of crisaborole in plasma at different time points were determined by LC-MS/MS. The pharmacokinetic parameters were calculated and the bioequivalence was compared by SAS9.4 program. Results: The pharmacokinetic parameters of crisaborole for test and reference preparations in fasting condition were as follows: C_max are 29.39 and 29.25 ng·mL^－1; AUC_0-t are 288.32 and 294.07 ng·h·mL^－1; AUC_0-∞ are 291.07 and 296.54 ng·h·mL^－1, respectively. The ratios of crisaborole test preparation and reference preparation C_max, AUC_0-t, AUC_0-∞ were 98.55%, 97.28%, and 97.35%, respectively. The 90% confidence intervals were 91.26%～106.41%, 90.20%～104.93%, and 90.37%～104.88%, respectively. Conclusion: The test and reference preparations of crisaborole ointment were bioequivalent in healthy Chinese subjects.

Objective: To study the chemical compounds and the mechanism against ovarian cancer of the water decoction of Curcumae Rhizoma-Sparganii Rhizoma. Methods: Chromatographic techniques were used to separate compounds, and their structures were identified using physicochemical and spectral analyses. The genes that are differentially expressed in ovarian cancer patients and normal controls were obtained from the GEO database. Protein-protein interaction network (STRING database, Cytoscape) was constructed to screen core targets. Molecular docking with active ingredients was  used to analyze target-ligand binding affinities. Results: 19 compounds were isolated and identified as furanocadina-1(10),6,8-triene-4-sulfonic acid (1), Curcolonol (2), Dihydrocurcolone (3), Phacadinane C (4), Zederone (5), Wenyujin K (6), Furanodienone (7), Germacrone (8), Zedoalactone B (9), Zedoarolide B (10), Curcumenol (11), Zedoarondiol (12), cyclo(Pro-Val) (13), cyclo(Ala-Pro) (14), cyclo(Leu-Pro) (15), d-corydaline (16), Tetrahydropalmatine (17), Adenosine (18), Uridine (19), including 12 sesquiterpenes and 7 nitrogen-containing. 2 239 genes that were differentially expressed was obtained by Bioinformatics analysis. Prostaglandin-endoperoxide synthase 1, progesterone receptor, DNA topoisomerase II Alpha and matrix metallopeptidase 1 were identified as core targets. A strong affinity between the active ingredient and the core target was found. Conclusion: Compounds 1~19 were isolated from water decoction of Curcumae Rhizoma-Sparganii Rhizoma for the first time, and compounds 13~17 were isolated for the first time from Curcumae Rhizoma or Sparganii Rhizoma. Drug pairs may exert anti-ovarian cancer effect through PTGS1, PGR, TOP2A and other targets.

Objective: To evaluate the cost-effectiveness of dupilumab plus background therapy compared with omalizumab plus background therapy in the treatment of severe asthma from the perspective of Chinese health system. Methods: A Markov model was established. The clinical efficacy, health benefit and cost data were obtained from the randomized controlled trials, published literatures and clinical expert consultation results. Lifetime disease outcomes, effectiveness, and costs under each intervention were calculated. With incremental cost-effectiveness ratio (ICER) as the index, the economy of each intervention was evaluated under the threshold of 2 times GDP per capita (178 716 yuan in 2023). Scenario analysis, one way sensitivity analysis and probability sensitivity analysis were carried out to verify the robustness of the results. Results: The total costs were 679 459 and 615 213 CNY in the groups of dupilumab and omalizumab, respectively. Total quality-adjusted life year (QALY) were 13.11 and 12.68. Compared with omalizumab, dupilumab increased costs by 64 246 CNY and QALY by 0.43. ICER was 149 661 CNY per QALY, which was lower than the 2 times per-capita GDP threshold, indicating that dupilumab was cost-effective compared with omalizumab. In the two scenarios set in the study, the group of dupilumab was more economical than the group of omalizumab. In the three scenarios set in the study, the group of dupilumab was more economical. If the negotiated price of dupilumab in the 2024 edition of the National Medical Insurance Drug List is used, the group of dupilumab is obviously superior. Sensitivity analysis verified the robustness of the above results. Conclusion: Under the threshold of 2-time Chinese GDP per capita, dupilumab is more cost-effective than omalizumab in the treatment of severe asthma patients.

Objective: To analyze the reports of hematologic adverse drug reactions (ADRs) induced by fulvestrant and investigate their clinical characteristics and risk factors. Methods: Cases of hematologic ADR associated with fulvestrant reported by our hospital from September 1, 2021 to December 31, 2023 were screened and analyzed to explore the features of these ADR. Results: The majority of patients who experienced ADRs were elderly individuals aged 70 years or older. The primary hematologic toxicities observed included leukopenia/neutropenia and thrombocytopenia, with two cases identified as new serious ADRs that had not been previously documented in the drug's prescribing information. Temporally, most ADRs occurred within 15 d after the first dose. Additionally, concomitant use of fulvestrant with CDK4/6 inhibitors (e.g., abemaciclib) or anti-HER2 targeted therapies was found to potentially exacerbate hematologic toxicity. In terms of management, most patients showed significant improvement after symptomatic treatment, including drug discontinuation, granulocyte colony-stimulating factor (G-CSF) infusion, and thrombopoietin administration. Conclusion: Fulvestrant, whether used as monotherapy or in combination regimens, may induce myelosuppression, particularly in elderly patients and when co-administered with other drugs. Enhanced blood monitoring during initial treatment and updates to ADR warnings in the prescribing information are recommended to optimize clinical safety.

Compound Phellodendron Liquid Coating has the effects of clearing heat, detoxifying, reducing swelling, and relieving decay. It is mainly used clinically for the treatment of damp heat stagnation and heat toxin accumulation syndrome. Modern clinical studies have demonstrated that the formulation exhibits robust safety profiles and significant therapeutic efficacy.In order to further standardize the clinical application of Compound Phellodendron Liquid Coating in the treatment of mixed hemorrhoids, our society organized the experts in relevant fields to conduct systematic discussions on the key issues such as clinical efficacy and drug safety evaluation based on existing evidence-based medicine. The ultimate objective is toestablish a consensus among experts, aiming to provide scientific and standardized medication guidance for clinical practice.