Abstract:Henoch-schönlein purpura nephritis(HSPN),a common chronic kidney disease in children,seriously affects the physical and mental health of the affected children.Exploring effective prevention and treatment strategies is of vital importance.Traditional Chinese medicine(TCM)has demonstrated unique advantages in this field.Scientifically and standardly designing clinical trials of TCM for the prevention and treatment of HSPN in children is crucial for guiding rational clinical use of TCM and promoting the clinical transformation of new TCM drugs.This study systematically integrated relevant domestic and international diagnosis and treatment guidelines,high-quality research evidence,and clinical practice experience to summarize and distill the core technical points for the design and evaluation of clinical trials of TCM for children with HSPN.It aims to construct a methodological system for pediatric TCM clinical trials that integrates the characteristics of TCM with the rigor of evidence-based medicine,promoting standardization of the diagnosis and treatment of integrated traditional Chinese and Western medicine of HSPN and the research and development of new TCM drugs for children.

Abstract:This article systematically reviews the safety and efficacy of the bispecific antibody ivonescimab in the treatment of advanced solid tumors,particularly non-small cell lung cancer(NSCLC).Multiple clinical trial results have shown that ivonescimab has good anti-tumor activity,can improve clinical outcomes,overcome resistance to programmed death-ligand(PD-L1)inhibitors,especially in PD-L1 positive and epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor(EGFR-TKI)resistant NSCLC,with significant efficacy and good safety.Its listing marks a significant advancement in dual antibody technology for the treatment of advanced NSCLC,which may reshape the treatment pattern of EGFR mutant and PD-L1 positive NSCLC and open up new ideas for the treatment of solid tumors.Future research should focus more on the long-term trial results and real-world applications of ivonescimab in the field of solid tumors,in order to better determine its application in solid tumors,especially NSCLC.

Abstract:Bronchial asthma is a common chronic airway disease in children.Based on domestic and international clinical trial protocols or reports in the past decade,the Global Initiative for Asthma,diagnostic and treatment guidelines,and technical guidance for clinical trials,combined with our team's practical experience,this study systematically reviews the essential aspects of clinical trials of traditional Chinese medicine(TCM)in treating pediatric bronchial asthma,such as clinical positioning,efficacy evaluation,overall trial design,diagnostic criteria,participant selection and withdrawal,treatment protocols,and safety monitoring.The aim is to provide scientific and standardized technical guidance for such clinical trials,thereby promoting further development of TCM-based drug research and development for pediatric asthma.

Abstract:Patient-derived bladder cancer organoids represent an emerging in vitro model system capable of retaining the histological and molecular characteristics of the primary tumor,accurately recapitulating the tumor microenvironment,and demonstrating stable passaging potential.Driven by the growing"animal-free"trend,organoids are increasingly recognized as vital tools for drug evaluation and translational research in bladder cancer.This article aims to systematically review the methodologies for constructing bladder cancer organoids,assess their consistency with parental tumor tissues,and explore their applications within drug evaluation and translational research,including pharmacodynamic assessment,precision medicine,and mechanism research,ultimately seeking to advance stand-ardization and broaden the scope of their utilization.

Abstract:Objective:To analyze the priority challenges in vaccine regulation in China and provide reference for the improvement of the national regulatory system.Methods:A list of possible challenges in vaccine regulation in China was generated through literature review and in-depth interviews.Using the Hanlon method,expert consultation was conducted to assess the importance,severity and feasibility of intervention for these potential challenges to screen out priority challenges.Results:The expert response rate was 83.5%,the expert authority coefficient was 0.772,and the coordination coefficients for expert scoring on the importance,severity,and feasibility of intervention of potential challenges were 0.576,0.517,and 0.510,respectively(P<0.05).According to the results of the Hanlon's analysis,the top five priority challenges in vaccine regulation in China were:inadequate development of regulatory human resources;an underdeveloped information disclosure and public communication mechanism;an incomplete quality management system within regulatory authorities;weak quality management capabilities in some enterprises;and insufficient coordination in accelerated regulatory processes.Conclusion:This study suggests that strengthening the development of professional human resources,improving mechanisms for information disclosure and public communication,enhancing quality management system construction,guiding enterprises to implement self-regulation,and coordinating accelerated regulatory mechanisms are five key dimensions for systematically advancing vaccine regulatory capacity and comprehensively improving the level of vaccine regulatory governance in China.

Abstract:Objective:To identify and analyze disproportionality signals of drug-related thyroid adverse reactions,summarize potentially high-risk drugs,and provide references for clinical medication safety.Methods:Reports of thyroid adverse events from the US Food and Drug Administration Adverse Event Reporting System(FAERS)between January 2004 and December 2024 were retrieved.Disproportionality analysis was used to assess drug-thyroid adverse event associations,with further evaluation of demographics,time to onset,and patient outcomes.Results:Among 1 261 drugs,80 exhibited signals of thyroid adverse reactions,including 39 antineoplastic agents(48.75%),7 anti-infectives(8.75%),6 cardiovascular drugs(7.5%),and 9 neurologic agents(11.25%).Amiodarone(2 537 cases),pembrolizumab(1 953 cases),and nivolumab(1 748 cases)were the most frequently reported agents.The strongest thyroid signal intensities(by ROR)were observed for biotin(ROR=164.57),amiodarone(ROR=61.51),bexarotene(ROR=46.85),and benzophenylamine(ROR=35.26).Females showed higher susceptibility(female-to-male ratio:1∶2.33),particularly in individuals aged 18～64 years(18352 cases,59.12%).Thyroid abnormalities associated with antineoplastic drugs had a shorter time to onset.Higher proportions of fatal outcomes were associated with digoxin,sorafenib,pembrolizumab,and nivolumab.Conclusion:Numerous drugs are associated with the risk of thyroid dysfunction,warranting vigilant monitoring.Females,especially those aged 18～64,represent a high-risk population for frug-related thyroid abnormalities.For antineoplastic agents,the first 60 days of treatment constitute a critical monitoring period;long-term medications demand regular surveillance.

Abstract:Objective:To establish an HPLC-PDA method for the simultaneous determination of 5-hydroxy-methylfurfural,chlorogenic acid,caffeic acid,isochlorogenic acid A,cichoric acid,baicalin,oroxylin A-7-O-β-D-glucuronide,wogonoside,baicalein and glycyrrhizic acid in the Puqin Jiedu Lishi Granules.Methods:The analysis was performed on a Waters Symmetry C18 column(250 mm×4.6 mm,5 μm)with gradient elution using acetonitrile and 0.2%phosphoric acid solution as the mobile phase.The flow rate was 1.0 mL·min-1,the column temperature was 20℃,and the detection wavelengths were set at 284 nm,327 nm,280 nm and 254 nm.Results:The linear ranges of 5-hydroxymethylfurfural,chlorogenic acid,caffeic acid,isochlorogenic acid A,cichoric acid,baicalin,oroxylin A-7-O-β-D-glucuronide,wogonoside,baicalein and glycyrrhizic acid were 1.860～59.64,5.425～173.6,1.980～63.36,1.890～60.24,5.990～191.6,33.30～1066,6.440～206.0,28.00～896.0,2.044～65.40,6.660～213.1 μg·mL-1,respectively,with the correlation coefficients r≥0.999 5.The precision,stability,and reproducibility tests yielded satisfactory results.The average recoveries of the 10 components ranged from 98.15%～102.21%,with RSDs between0.96%～1.91%.Conclusion:This method is reliable,stable and reproducible,providing a reference for the quality control of Puqin Jiedu Lishi Granules.

Abstract:Micron-scale tablets(1 000～3 000 μm),driven by the dual forces of Pharmaceutical Industry 4.0 and precision medicine,have emerged as a core carrier for pediatric and personalized treatment due to their exceptional dose flexibility and multi-unit delivery advantages.The quality by design(QbD)concept provides a systematic framework to overcome key industrialization bottlenecks-such as poor flowability at high drug loads,challenges in achieving blend uniformity for ultra-low-dose formulations,and stringent sensitivity requirements for miniaturized quality control-facilitating the successful establishment of a multidimensional"structure-process-quality"correlation model in the field.Research advances demonstrate that the integration of multimodal spectral imaging(HSI-FT-NIR coupling)with neural network fusion technology enables real-time tracking of content uniformity and release profiles at the millimeter level,facilitating the formation of a full-chain quality control closed-loop from process analysis to dynamic release.The integrated application of innovative technologies such as hot melt extrusion-based microfluidic 3D printing offers new pathways for constructing complex functional dosage forms like colon-targeted and gastric-floating tablets.This review further examines the challenges and breakthrough directions for intelligent upgrades in continuous manufacturing under the QbD framework and outlines interdisciplinary pathways and future prospects for the efficient clinical translation of micron-scale tablet technologies.

Abstract:Drug transporters are critical membrane proteins that facilitate the transmembrane transport of drugs,endogenous molecules,and toxins via ATP hydrolysis or ion/concentration gradients.These transporters significantly impact drug absorption,distribution,metabolism,and excretion,and are essential to drug safety and efficacy.They are classified two major families:ATP-binding cassette(ABC)transporters and solute carrier(SLC)transporters.Single nucleotide polymorphisms in transporter genes have a significant influence on drug metabolism and individual variability.In recent years,advances in genomics have led to increasing reports linking transporter gene polymorphisms to differences in drug disposition and clinical efficacy.This paper reviews some key polymorphisms in drug transporters that are associated with anti-cancer drug disposition,with the aim of supporting rational clinical drug use and facilitating personalized anti-cancer therapy.

Abstract:Through analysis of the on-site inspections of registration and manufacturing of innovative therapeutic biological products,the application and inspection initiation status of such products from 2021 to 2023 were reviewed.Common issues identified in the corresponding inspection reports were categorized and analyzed,and then suggestions to offer valuable references for drug registration applicants in the development and registration of innovative therapeutic biological products were provided.The aim is to support continuous improvement in pharmaceutical production management,enhance quality risk management capabilities,and promote the implementation of drug lifecycle management.

Abstract:Objective:To investigate the effects and underlying mechanisms of Heqi San in improving insulin resistance in newly diagnosed type 2 diabetes mellitus(T2DM).Methods:Network pharmacology was employed to predict the key targets and signaling pathways involved in Heqi San's intervention in T2DM-related insulin resistance.A rat model of T2DM with insulin resistance was then established.Animals were divided into five groups:normal control,model,metformin,high-dose Heqi San,and low-dose Heqi San.The effects of Heqi San on blood glucose,insulin resistance,lipid levels,and hepatic histopathological changes were evaluated.Western blot and ELISA were used to detect the expression of key proteins and inflammatory cytokines in liver tissue and serum to verify the accuracy of the network pharmacology predictions.Results:Network pharmacology analysis predicted that Heqi San may act through multiple targets,particularly by modulating the AGEs/RAGE/PI3K/AKT signaling pathway.In vivo experiments demonstrated that high-dose Heqi San significantly reduced fasting blood glucose and HOMA-IR index,alleviated insulin resistance and dyslipidemia,and ameliorated hepatic steatosis.Mechanistically,Heqi San inhibited the expression of AGEs and RAGE,suppressed NF-κB activation,reduced inflammatory cytokines TNF-α and IL-6,relieved inhibition of the PI3K/AKT pathway,increased GLUT2 expression,and enhanced hepatic glucose metabolism.Conclusion:Heqi San improves insulin signaling by modulating the AGEs/RAGE/PI3K/AKT pathway,thereby alleviating hepatic insulin resistance,regulating lipid and glucose metabolism,and exerting hypoglycemic,lipid-lowering,and hepatoprotective effects.These findings provide experimental evidence supporting the use of Heqi San in the treatment of newly diagnosed T2DM insulin resistance.

Abstract:Objective:To establish an ELISpot method for detection of antigen-specific T cell immune response of rats to tetanus vaccine.Methods:Based on the SD rat animal model,a dynamic monitoring strategy was adopted after immunization with a single dose of vaccine.Blood samples were collected before the first day of administration and on Day 14 and 28 to isolate PBMC,and key parameters such as the concentration of peptide stimulus and the ratio of positive controls were systematically optimized to establish an interferon-γ ELISpot detection method(IFN-γ ELISpot).The level of T cell immune response to the vaccine was quantitated.Results:The optimal concentration of peptide stimulus was determined to be 5 μg·mL-1·peptide-1,and the optimal positive control stimulus and concentration was20ng·mL-1 PMA+0.4μg·mL-1 Ionomycin.Nine dominant polypeptide sequences that could effectively stimulate T cell response were identified.Conclusion:The established method shows good performance in detecting the cellular immunity level after immunization with tetanus vaccine.

Abstract:Objective:The link prediction analysis explores the technological frontier of radiopharmaceuticals,identifies potential technological opportunities,and provides a scientific basis for R&D decision-making.Methods:This study constructed a prediction analysis framework containing four modules:patent text mining based on TF-IDF;constructing a keyword co-occurrence network and analyzing network characteristics and interaction trends;identifying potential technological opportunities by using similarity-based link prediction algorithms;and evaluating technological opportunities through indicators such as growth rate and technological influence.Results:It was found that the patent data from 1969-2023 indicated a continuous innovation trend in the field of radiopharmaceuticals;the network analysis showed that the technology interactions showed small-world characteristics and a high degree of technology interactions;the link prediction results identified multiple potential technological opportunities,and the drugs were found to have a significant potential for associating with Trop2,CD47,and so on.Conclusion:The recommendation results derived from the link prediction algorithm can provide decision-making reference for enterprise cooperation and provide references for researchers to select research direction.

Abstract:With the continuous development of modern biotechnology,monoclonal antibody,as an important and rapidly growing biotechnology product,plays an increasingly important role in disease treatment,diagnosis and bioscience research.Monoclonal antibodies have been widely used in the treatment of tumors,autoimmune diseases,infectious diseases,and transplant rejection.Although traditional immunoassays are technically straightforward,they are constrained by antibody cross-reactivity,limited dynamic range,and challenges in simultaneously detecting low-abundance monoclonal antibodies and their metabolites within complex biological matrices.In recent years,liquid chromatography-tandem mass spectrometry(LC-MS/MS),as a highly sensitive,highly selective,rapid,and efficient analytical tool,has shown important application value in the analysis of monoclonal antibodies.The purpose of this paper is to review the biological analysis methods of monoclonal antibody,focusing on the detection methods,pre-treatment methods,key steps,and challenges,so as to provide references for further promoting the development of mass spectrometry-based quantitative techniques for monoclonal antibody drugs.

Abstract:Orally delivered engineered bacteria hold significant promise for treating conditions such as inflammatory bowel disease,intestinal infections,cancer,and metabolic disorders.Compared to administration routes such as injection,oral delivery offers enhanced simplicity,improved patient compliance,and a lower risk of systemic infection.However,multiple physiological barriers-including gastric acid,bile salts,digestive enzymes,and the mucus layer-often lead to substantial loss of bacterial viability before reaching the target site.Recent advances in synthetic biology and material surface engineering have provided new strategies to overcome these challenges.This review systematically summarizes the design strategies for oral bacterial delivery systems,focusing primarily on genetic engineering and surface modification,and discusses their representative applications along with in vivo therapeutic validations.We conclude that the integration of genetic circuit regulation and functional surface modification can synergistically enhance colonization capacity,targeting precision,and treatment safety of engineered bacteria in the complex gut environment,representing a core direction for advancing oral bacterial therapeutics.Future efforts should focus on developing more intelligent genetic circuits and more precise surface functionalization strategies,alongside rigorous validation of their safety and efficacy in clinical translation,to expedite the real-world application of these living therapeutics.

Abstract:Suzetrigine,a novel oral non-opioid analgesic,was approved by the U.S.FDA on January 30,2025,for managing moderate-to-severe acute pain in adults.It relieves pain by targeting the peripheral nervous system to inhibit signal transmission.The drug specifically inhibits the voltage-gated sodium channel subtype 1.8(Nav1.8)predominantly expressed in peripheral nerves,which plays a critical role in the rising phase of action potential and is closely associated with nociceptive signaling.Suzetrigine demonstrated significant efficacy in managing postoperative pain after abdominoplasty and bunionectomy in clinical trials,with no addiction risk.This review comprehensively summarizes the pharmacological profile of suzetrigine,including its mechanism of action,pharma-codynamics,pharmacokinetics,drug-drug interactions,safety evaluation,and the results of clinical trials.

Abstract:Objective:To evaluate the cost-effectiveness of mirogabalin compared with pregabalin in the treatment of diabetic peripheral neuropathic pain(DPNP).Methods:Based on secondary literature review,a network meta-analysis was conducted to obtain the data on the efficacy and safety of mirogabalin and pregabalin in the treatment of DPNP.Then,a Markov model was used from the Chinese healthcare system perspective.The health outcome indicator was quality-adjusted life years(QALYs),the time horizon was set as one year,and the economic outcome indicator was the incremental cost-effectiveness ratio(ICER).Sensitivity analysis was performed on the key parameters to verify the robustness of the results.Results:Mirogabalin could reduce the pain score more than pregabalin,and the difference was 0.28 points(95%CI:-0.043～0.60).The ICER of mirogabalin compared with pregabalin was 74 206.13 yuan·QALY-1,which was lower than the per capita GDP of China(2023,89 358 yuan).One-way sensitivity analysis showed that the utility values and drug costs were the main influencing factors.Conclusion:Based on current price,compared with pregabalin,mirogabalin is more cost-effective in the treatment of DPNP.

Abstract:Objective:This study aimed to assess the clinical efficacy and safety of Shenyu Ningshen Tablets(NYYX)in the treatment of mild-to-moderate depression.Methods:In this multicenter,randomized,double-blind trial,572 eligible participants(CCMD-3-diagnosed,baseline HAMD-17:14～24)were allocated to three arms:NYYX(2.4 g thrice daily,n=344),fluoxetine(10 mg·d-1 first week,20 mg·d-1 subsequent weeks,n=115),and placebo(n=113)for 8 weeks.The primary endpoint compared adjusted mean differences in HAMD-17 score changes from baseline using modified intention-to-treat analysis,with non-inferiority margin prespecified as Δ=2.5 against fluoxetine and superiority testing versus placebo.Results:After 8 weeks of treatment,the NYYX group demonstrated a mean reduction in HAMD-17 score of 10.50±4.46 points,which was significantly greater than that of the placebo group(7.03±5.07,P<0.05)and achieved non-inferiority to fluoxetine(10.13±3.94;adjusted difference:-0.25,97.5%CI:-1.18 to 0.68).Safety assessments revealed no treatment-related adverse events in the NYYX group(0%),in contrast to 8.8%incidence in fluoxetine recipients(P<0.01).Conclusion:NYYX exhibits non-inferior antidepressant efficacy to fluoxetine with enhanced tolerability,positioning it as a viable botanical alternative for mild-to-moderate depression.These findings advance evidence-based integration of traditional Chinese medicine into mainstream psychiatric therapeutics.

Abstract:Objective:To review the case reports of erythrodermic skin lesions caused by dupilumab,analyze the occurrence rules and characteristics,and provide references for clinical safe and rational drug use.Methods:The cases of erythrodermic skin lesions caused by dupilumab were analyzed by searching CNKI,Wanfang Data,Vipnet,PubMed,Web of Science,and other databases.Results:There were 6 cases of erythrodermic skin lesions caused by dupilumab,involving a total of 8 patients,including 7 males and 1 female,aged from 26 to 82 years old,which occurred within 3 to 150 days after medication,mostly within 2 weeks after medication.The main involved areas were the face,trunk,and limbs.The recovery time was mostly within 7 to 20 days.After improvement,5 patients re-used the drug,among whom 2 patients did not have recurrence,and 3 patients had recurrence,but the severity and recovery time were reduced and shortened compared with the previous occurrence.Conclusion:Clinicians should pay close attention to the erythrodermic skin lesions of dupilumab and strengthen monitoring during medication to facilitate timely diagnosis and treatment,ensuring medication safety.

Abstract:B7H7 shows a relatively limited expression profile in healthy tissues,but is highly expressed in a wide range of human cancers.There is no significant co-expression pattern between B7H7 and other B7 family members,suggesting its potential as an independent immune checkpoint in cancer patients.This characteristic may provide therapeutic opportunity for programmed death-1(PD-L1)negative and refractory tumors,thereby expanding the coverage of cancer treatment.Therefore,targeting B7H7 represents a promising treatment approach for patients unresponsive to PD-1/PD-L1 inhibitors.In-depth analysis of B7H7-related patent information will provide strong support for the research,development and innovation of such drugs.This article uses patent intelligence analysis methods to analyze the application trend of B7H7-related patents,the distribution of patent regions,and important innovation entities based on the retrieved global patent data related to the technology.Statistical analysis reveals that the number of global B7H7 patents is still in an early growth stage.The United States and China lead in terms of patent applications,with the United States actively pursuing patent protection in major global market and demonstrating high patent quality.In view of these findings,it is suggested that China focus on the research and development in the monoclonal antibody field,rationally optimize resource allocation,and avoid blind and clustered investment,so as to promote the rapid development of the tumor treatment field in China.