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2026 Volume 35 Issue 11  Published: 2026-06-15
  • Sheng-yan GENG
    doi: 10.20251/j.cnki.1003-3734.2026.11.001

    With the advancement of Sino-US trade negotiations and the revision of relevant chapters on supplementary experimental data in the Patent Examination Guidelines, the number of administrative and judicial cases in which supplementary experimental data are the focus of dispute has shown a significant upward trend in recent years. At the same time, however, the trial processes of individual cases have also revealed certain controversial characteristics. This article comprehensively reviews the relevant provisions of the Patent Examination Guidelines and typical adjudication rules in the judicial field, and summarizes the approaches and methods for judging the "three facts" and the "three pairs of relationships" in the trial of supplementary experimental data. It then provides an in-depth analysis of representative administrative decisions and judicial judgments in recent years. On this basis and taking into account the characteristics of the trial practice, suggestions are put forward for the key steps in the trial of supplementary experimental data, so as to objectively and reasonably evaluate the issues related to supplementary experimental data under China's institutional framework for supplementary experimental data, continuously enhance the consistency and predictability of trials involving supplementary experimental data, and thereby help promote the innovative and high-quality development of China's pharmaceutical industry.

  • Zhong-jian FANG , Cheng-ling SHI , Li-you CUI , Li-ping CHEN , Yong-zhe MA , Jun-wen LU , Hai-cheng FANG , Yu-lu FAN
    doi: 10.20251/j.cnki.1003-3734.2026.11.002

    Under the strategic frameworks of the "Belt and Road Initiative" and Regional Comprehensive Economic Partnership, Southeast Asia has emerged as a critical region for the international expansion of traditional Chinese medicine (TCM) enterprises. However, the complexity of the market environment presents significant barriers to traditional internationalization pathways, necessitating the development of innovative strategic mechanisms tailored to local market characteristics. Employing game theory as the analytical foundation, this study constructed three strategic game models: signaling games for institutional entry, non-zero-sum cooperative games for resource integration, and evolutionary games for consumer cultural acceptance. Using Singapore, Malaysia, and Indonesia as representative markets, the research comparatively analyzed variations in institutional environments, cultural receptivity, and competitive structures. Empirical analysis of typical enterprises such as Pien Tze Huang and Tongrentang validated the effectiveness and differentiation of strategic pathways across various game-theoretic scenarios. The results indicated that internationalization strategies for TCM enterprises should emphasize proactive institutional signaling, sustainable non-zero-sum cooperative alliances, and the long-term cultivation of consumer cultural cognition, thereby achieving a dynamic equilibrium among institutions, resources, and culture. By introducing a game-theoretic perspective, this paper enriches the theoretical approaches to TCM internationalization strategies and provides practical insights for enterprises navigating culturally heterogeneous markets. The theoretical innovation of this study lies in its novel application of game theory to analyze strategic adaptation mechanisms of TCM enterprises in Southeast Asian markets, thereby offering concrete strategic guidance for enterprises aiming for breakthroughs in their internationalization processes.

  • Yi-fei DAI , Yu-jia XIE , Tao JIANG , Zhi-jun TU , Ming-hong WANG , Feng REN
    doi: 10.20251/j.cnki.1003-3734.2026.11.003

    Radionuclide drug conjugates (RDCs) have shown great potential in the field of nuclear medicine due to their precise targeting and radioactive killing capability. This article comprehensively reviews the selection criteria of radionuclides in RDCs and various conjugation strategies between radionuclides and targeting ligands, and provides an in-depth discussion on the differences in quality control for different radionuclides, aiming to provide a reference for the pharmaceutical research and evaluation of RDCs, and help realize their integrated precision diagnosis and treatment in more diseases.

  • Chao CHEN , Hui-nan XU , Jing PAN , Bo SHEN
    doi: 10.20251/j.cnki.1003-3734.2026.11.004

    Immune cell therapy products have demonstrated favorable therapeutic outcomes in the treatment of certain tumors. This article briefly descibes the application status of immune cell therapy products in China. By combining the pharmaceutical issues in investigational new drug (IND) applications and the common issues in regulatory communications for such products, and with reference to relevant domestic and international regulations as well as technical guidelines, it exemplifies the general considerations for pharmaceutical research in IND applicaitons of immune cell therapy products, focusing mainly on raw materials for production (cells for production, in vitro modification systems, and other raw materials for production), manufacturing processes, and quality research and control, in order to provide a reference for the research, development, and application of such products and to promote their clinical translation.

  • Yu-shan GUO , Ai-lin ZHANG , Yu-tong LIU , Da-peng TONG , Yu-tong MEI , Yan-hong WANG
    doi: 10.20251/j.cnki.1003-3734.2026.11.005

    As a drug delivery system capable of painlessly penetrating biological barriers, microneedles (MNs) are often limited in their application by issues such as the need for secondary needle removal and infection risks. Natural polysaccharides, due to their excellent biocompatibility, degradability, and biological activity, are regarded as novel MN materials that can overcome these limitations. Natural polysaccharide-based MNs can effectively penetrate biological barriers and gradually degrade in the dermis to achieve sustained drug release, demonstrating good therapeutic effects in the treatment of various diseases. Moreover, the combined application of natural polysaccharide-based MNs and nano drug delivery systems (NDDS) provides a new approach for the intelligent and precise development of natural polysaccharide-based MNs. This article summarizes the performance differences of MNs prepared from polysaccharides of different sources, and reviews the practical applications of combined drug delivery with polysaccharide-based MNs and NDDS, aiming to provide a theoretical basis for further research on natural polysaccharide-based MNs and to promote their further development in the field of drug delivery.

  • Ru ZHANG , Xin SUO , Wen-rong LIU , Ying-mei LI , Shui-xiang WANG , Xia DOU , Xin-rong YANG , Zi-ming JIN
    doi: 10.20251/j.cnki.1003-3734.2026.11.006

    Major depressive disorder (MDD) is a common psychiatric disorder characterized primarily by persistent low mood. With a high global prevalence, it has become one of the leading causes of the global disease burden. Current clinical treatment for MDD primarily relies on Western medicine, but issues such as frequent adverse reactions and high recurrence rates persist. Traditional Chinese medicine (TCM), leveraging its advantages of multi-target, multi-pathway action and fewer adverse reactions, demonstrates unique potential in MDD treatment. Bupleuri Radix (Chai Hu), a key herb in TCM for soothing the liver and resolving depression, possesses effects such as dispersing heat, soothing the liver and resolving depression, and elevating yang qi. Its role in the prevention and treatment of MDD has garnered significant attention in recent years. This paper systematically reviews recent studies on Bupleuri Radix's antidepressant effects, identifying saponins, flavonoids, and volatile oils as its core active components. Its mechanisms primarily involve regulating neurotransmitter balance, improving hypothalamic-pituitary-adrenal (HPA) axis dysfunction, protecting neural plasticity, suppressing neuroinflammation, modulating the "microbiome-gut-brain axis," and counteracting oxidative stress. This review covers Bupleuri Radix's active antidepressant components, mechanisms of action, and compound applications, providing a reference for the development, utilization, and clinical application of Bupleuri Radix and its active constituents.

  • Yan-mei ZHANG , Chang-hui ZHOU , Hong-yan SU , Bin YANG , Yan-xin LU , Hua LI
    doi: 10.20251/j.cnki.1003-3734.2026.11.007

    Glomerular filtration rate (GFR) serves as a critical indicator for assessing renal function, and its accurate measurement is essential for preclinical studies, clinical research, and fundamental research. This article systematically reviews the recent advances in GFR detection methods, including the application of endogenous markers (creatinine, blood urea nitrogen, and cystatin C) and exogenous markers (inulin, iohexol, fluorescein isothiocyanate (FITC)-sinistrin, and radiolabeled compounds), as well as emerging techniques such as in vivo fluorescence imaging. While endogenous markers offer operational convenience, their accuracy is limited by susceptibility to non-renal factors. Among exogenous markers, although inulin is the gold standard, its procedure is cumbersome, whereas FITC-inulin and iohexol achieve a balance between non-invasiveness and accuracy but still require optimization. Emerging technologies, such as multiphoton high-resolution fluorescence imaging, enable dynamic monitoring of single-nephron GFR, although challenges persist in the assessment of overall renal function. Future development should focus on non-invasive, high-precision, and continuous monitoring approaches. This article provides methodological references for renal function research and discusses future trends in technological innovation, aiming to serve as a reference for those involved in preclinical and clinical studies of renal function and the development of GFR monitoring techniques.

  • Jian-pei XU , Shun-wei ZHU , Rong CHEN , Shan-seng XU , Jian REN , Lan WANG , Feng WANG
    doi: 10.20251/j.cnki.1003-3734.2026.11.008

    The incidence and disease burden of myocardial and cerebral infarction is rising annually, creating an urgent need for effective therapeutic drugs. Cardiac and cerebral ischemic infarction has an acute onset and rapid progression, resulting in high mortality and disability rates. Rapid treatment and tissue protection within the golden therapeutic time window are the keys to improving prognosis and reducing disease burden. Traditional oral drugs have a slow onset and significant first-pass effect, while intravenous thrombolysis and interventional therapy are limited by medical conditions and cannot be widely accessible to patients. Sublingual tablets, with rapid absorption and convenient administration unrestricted by region or medical resources, have become the preferred dosage form for emergency treatment. Sublingual nitroglycerin tablets have revolutionized the emergency treatment landscape of myocardial infarction, whereas cerebral infarction emergency treatment still faces medication difficulties. Edaravone dexborneol sublingual tablets have demonstrated a clear cerebral protective effect with rapid brain penetration, meeting the medication needs of patients with dysphagia in various settings both inside and outside the hospital. Moreover, they are superior to injections in terms of production, transportation, administration, and storage costs, exhibiting high cost-effectiveness and good efficacy, and are expected to change the current emergency treatment situation of cerebral infarction. This article summarizes the research progress on sublingual tablets formulations based on the pathological features of cardiac and cerebral infarction, aiming to provide new ideas for drug development in the treatment for these diseases.

  • Jia-pei YANG , Wei WU , Xiu-hua LU , Hong-yan FAN
    doi: 10.20251/j.cnki.1003-3734.2026.11.009
    Objective:

    To analyze the characteristics and trends of traditional Chinese medicine (TCM) clinical trials registered in China from 2013 to 2024, and to provide a reference for the development of new TCM drugs and clinical research strategies.

    Methods:

    All TCM clinical trials registered on the National Medical Products Administration Drug Clinical Trial Registration and Information Disclosure Platform from its inception to December 31, 2024, were retrieved. A descriptive statistical analysis was conducted from multiple dimensions, including the number of trials, phases, design types, drug dosage forms, indications (classified using ICD-11 codes), and leading institutions.

    Results:

    A total of 1 125 TCM clinical trials were included, accounting for 4.03% of all registered trials during the same period. From 2013 to 2024, the annual number of registered TCM clinical trials did not show a significant growth trend, and their proportion relative to all clinical trials showed a declining trend. The trials were predominantly domestic multi-center studies (99.73%), with Phase II trials constituting the highest proportion (59.20%). A randomized, double-blind, parallel-controlled design was used in 86.31% of the trials. The rates of data safety monitoring committee establishment (3.64%) and subject insurance coverage (32.09%) were low. Oral dosage forms (capsules, granules, tablets, etc.) were the most common (85.87%). Indications were concentrated in respiratory system diseases (21.69%), digestive system diseases (15.64%), and urogenital system diseases (13.51%). The geographical distribution of leading institutions was highly concentrated, with Beijing, Tianjin, and Shanghai collectively accounting for 55.64% of the total.

    Conclusion:

    While progress has been made in the standardization of TCM clinical trial design in China, overall development remains slow, with challenges including low international participation, insufficient subject protection measures, and imbalanced distribution across research areas and regions. It is recommended to introduce targeted incentive policies, encourage exploration of innovative formulations and difficult-to-treat diseases, strengthen subject rights protection, and promote the high-quality and sustainable development of TCM.

  • Lin-wan CHEN , Zhou-li WANG , Wei-jun CHEN , Li-peng QIU , Dong-kai WANG
    doi: 10.20251/j.cnki.1003-3734.2026.11.010
    Objective:

    To prepare a targeted delivery system of quercetin metal complex loaded with doxorubicin and to investigate its pharmaceutical properties and anti-tumor capability.

    Methods:

    With quercetin as the ligand, the optimal bimetallic complex carrier was prepared and screened by adjusting the molar ratios of manganese to copper, and the drug-loaded nanoparticles with the best encapsulation efficiency and drug loading were screened by further adjusting the dosage of doxorubicin. Finally, the targeted drug delivery system was prepared by chondroitin sulfate modification. The physicochemical properties of the nanoparticles such as particle size, Zeta potential, infrared spectrum and ultraviolet spectrum, were characterized. Then, the in vitro drug release behavior, glutathione (GSH) degradation capability, reactive oxygen species (ROS) production capability and blood compatibility were investigated. Finally, the safety and anti-tumor activity were investigated using 3T3 and B16F10 cell lines.

    Results:

    The blank carrier synthesized at the optimal manganese-copper ratio of 2∶1 exhibited the best anti-tumor activity. When the dosage of doxorubicin was 0.05 mmol·L-1, the prepared nano-delivery system had the best drug loading and encapsulation efficiency, which were (15.89±0.34)% and (90.21±0.45)%, respectively. A targeted drug delivery system was then prepared after modification with 30% chondroitin sulfate. Various characterizations confirmed the successful preparation of the bimetallic complex targeted drug delivery system, with suitable particle size and high encapsulation efficiency and drug loading. The delivery system showed good drug release under pH 5.0 condition containing 10 mmol·L-1 GSH, and exhibited favorable GSH degradation capability, ROS production capability, blood compatibility, cytocompatibility, and tumor cytotoxicity.

    Conclusion:

    In this study, a targeted drug delivery system loaded with doxorubicin metal complexes was successfully prepared by screening the metal ratio and doxorubicin dosage, followed by chondroitin sulfate modification. The system achieved high drug loading and favorable drug release behavior. This therapeutic strategy using quercetin metal complexes and doxorubicin exerts synergistic anti-tumor effects through combined chemotherapy and chemodynamic therapy, which may provide new ideas for enhancing synergistic anti-tumor efficacy.

  • Ting-ting WANG , Man-shu ZOU , Hai-peng GUO , Xiao-shi YU , Yao ZHANG , Zi-xuan XIANG , Hai-long SU , Yu-hong WANG , Yuan-shan HAN
    doi: 10.20251/j.cnki.1003-3734.2026.11.011
    Objective:

    To investigate the mechanism of the P2X purinoceptor 7 (P2X7)-NOD like receptor family pyrin domain containing 3 (NLRP3) pathway in diabetes mellitus with depression (DD).

    Methods:

    Sixty Sprague Dawley (SD) rats were randomly divided into six groups (n=10 per group): control (Con), diabetes mellitus (DM), depression (Dep), diabetes mellitus with depression (DD), positive drug [metformin (0.18 g·kg-1)+fluoxetine (1.8 mg·kg-1)] (Y), and P2X7 inhibitor [Brilliant Blue G (BBG), 30 mg·kg-1]. DD rat models were established using 4 weeks of high-fat diet feeding combined with intraperitoneal streptozotocin (STZ) injection, followed by 4 weeks of chronic unpredictable mild stress (CUMS) combined with single caging. Rats in the inhibitor group received daily intraperitoneal injections starting from day 15 of modeling for 14 consecutive days. After modeling and drug intervention, behavioral tests (open field test, forced swim test, Morris water maze) were used to assess depression-like behaviors and cognitive function. Serum levels of norepinephrine (NE), 5-hydroxytryptamine (5-HT), and dopamine (DA) were measured by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was performed to detect hippocampal P2X7/Iba-1, NLRP3/Iba-1, postsynaptic density protein-95 (PSD95), and synapsin-1 (SYN1). Hippocampal neuronal damage was assessed using hematoxylin-eosin (HE) and Nissl staining. Western blotting was used to measure the expression of P2X7-NLRP3 axis-related proteins (P2X7, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, interleukin-1β (IL-1β) and brain-derived neurotrophic factor (BDNF).

    Results:

    Both BBG and the positive drug effectively attenuated the loss of body weight and elevated fasting blood glucose in DD rats. Behavioral results showed that BBG and the positive drug reduced immobility time in the forced swim test, increased total distance traveled and total activity in the open field test, shortened escape latency, and increased the time spent in the target quadrant in the Morris water maze. Pathological results demonstrated that BBG and the positive drug ameliorated neuronal damage in the hippocampal region of DD rats. Biochemical analysis results indicated that BBG and the positive drug upregulated serum levels of 5-HT, DA, and NE. Immunofluorescence and Western blot results showed that BBG could reduce the expression of P2X7 and NLRP3 in the hippocampus, while increasing the expression of PSD-95, SYN-1, and BDNF.

    Conclusion:

    BBG exerts neuroprotective effects by inhibiting the P2X7/NLRP3 axis and hippocampal microglial activation, thereby ameliorating neuroinflammation and abnormal NLRP3 inflammasome activation. This leads to increased expression of synaptic-related proteins (PSD95, SYN) and BDNF in the hippocampus.

  • Meng GAO , Yu-pei WU , Miao-miao WANG , Hui-zhen WU
    doi: 10.20251/j.cnki.1003-3734.2026.11.012
    Objective:

    To mine the adverse events (AEs) related to bevacizumab in ovarian cancer patients from the FDA Adverse Event Reporting System (FAERS) and to reveal their clinical priority information, so as to provide a reference for clinical medication.

    Methods:

    AE reports related to bevacizumab for ovarian cancer were collected from the FAERS database from the first quarter of 2004 (Q1) to the first quarter of 2025 (Q1). Signal mining was performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR) and Bayesian Confidence Propagation Neural Network (BCPNN) methods, and clinical priority assessment of positive signals was conducted.

    Results:

    A total of 5 025 reports were include. Physicians were the primary reporters (60.23%), and the United States accounted for the largest proportion of reporters (36.16%). A total of 195 preferred term (PT) signals were identified, spanning 20 System Organ Classes (SOCs). General disorders and administration site conditions was the most frequently reported SOC. Common AEs included hypertension, proteinuria and neutropenia, etc. The median onset time of all AEs was 81 days. Clinical priority classification: 2 PTs were classified as strong priority, 62 PTs as moderate priority, and 131 PTs as weak priority. The strong priority PTs were intestinal perforation and gastrointestinal perforation.

    Conclusion:

    Based on an extensive analysis of the post-marketing international safety database, this study identified common AEs associated with bevacizumab in ovarian cancer patients, and highlighted the need for close monitoring of intestinal perforation and gastrointestinal perforation, providing a reference for clinical medication and pharmacovigilance.

  • Jia-hui GU , Jian-qun ZHAO , Qing-yu CHEN , Yan-li CAO , Yin-ling MA
    doi: 10.20251/j.cnki.1003-3734.2026.11.013
    Objective:

    To mine the adverse drug event (ADE) signals of raltegravir and dolutegravir based on the FDA adverse event reporting system (FAERS) database, and provide references for clinical medication safety and rational drug selection.

    Methods:

    All ADE reports of raltegravir from the fourth quarter of 2007 to the fourth quarter of 2024 and dolutegravir from the third quarter of 2013 to the fourth quarter of 2024 in the FAERS database were mined using reporting odds ratio (ROR) and proportional report ratio (PRR).

    Results:

    After excluding all kinds of injuries, poisoning, and operation complications, as well as other unrelated signals such as all kinds of operations and medical operations, product problems and social problems, there were 4 136 ADE reports related to raltegravir, 288 effective signals were obtained, and the signals involved 23 system organs; there were 2 119 cases of dolutegravir-related ADE reports, 165 effective signals were mined, and 22 system organs were involved. The related ADE signals with significant differences between raltegravir and dolutegravir were mainly concentrated in nervous system disorders, psychiatric disorders, infections and infestations, blood and lymphatic system diseases, pregnancy, puerperium and perinatal conditions, congenital, familial and genetic diseases, and eye diseases, etc. Dolutegravir had a higher risk of ADEs in nervous system disorders and psychiatric disorders, while raltegravir had a higher risk in other disease-related ADEs.

    Conclusion:

    The study found that there is a significant difference in the risk of adverse events between raltegravir and dolutegravir in the treatment of acquired immunodeficiency syndrome, which can provide references for individualized clinical treatment.