Abstract: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.

Abstract:Objective:This study aimed to conduct a comprehensive clinical evaluation of hyzetimibe,establishing an evidence-based foundation for its rational and standardized clinical use while providing references for relevant drug policy formulation.Methods:Following established guidelines,a rapid assessment methodology was employed.Evidence was synthesized through a systematic literature review.Within the context of currently marketed cholesterol absorption inhibitors in China,a multidimensional evaluation of hyzetimibe for treating primary hypercholesterolemia was conducted across six domains:safety,efficacy,economic efficiency,innovation,suitability,and accessibility.Results:Hyzetimibe demonstrated a safety profile comparable to that of ezetimibe with no significant differences observed,indicating manageable safety risks.It effectively reduced LDL-C,non-HDL-C,total cholesterol(TC),and Apo B levels in patients with primary hypercholesterolemia.When used in combination of statin therapy,hyzetimibe significantly enhanced the efficacy of LDL-C reduction beyond what is achieved with statin monotherapy alone.For patients who failed to achieve lipid targets with statins alone,combination therapy with hyzetimibe facilitated goal attainment,and potentially reduced cardiovascular event risks associated with suboptimal lipid control and subsequent treatment costs,suggesting a cost-effectiveness advantage.The drug exhibits innovative characteristics in structural optimization,metabolic pathways,and indigenous research and development,demonstrating both clinical value and social significance.With convenient oral administration and favorable short-and long-term tolerability profiles,it is suitable for statin-refractory patients or those requiring statin dose reduction.Patients with mild to moderate hepatic or renal impairment showed good tolerance without adverse events reported.Hyzetimibe is widely available across all 32 provincial-level administrative regions in China;its utilization has been steadily increasing along with reliable supply chains.Conclusion:As the first independently developed novel selective cholesterol absorption inhibitor in China,hyzetimibe is similar to ezetimibe in mechanism of action,efficacy,and safety,but has certain local advantages in chemical structure,production process(localization),and drug cost control.Combination with hyzetimibe shows potential cost-effectiveness advantages when LDL-C reduction targets cannot be achieved with statin monotherapy.

Abstract:With the rising global prevalence of obesity,the limitations of lifestyle interventions and traditional anti-obesity drugs have become increasingly prominent,making the research and development of novel anti-obesity drugs a focal point in this field.Glucagon-like peptide-1(GLP-1)receptor agonists and their derived dual-target drugs,relying on their significant anti-obesity efficacy and relatively good safety profile have emerged as an effective therapeutic regimen for obese patients.This article summarizes the clinical pharmacology factors of these anti-obesity drugs,including their pharmacokinetic and pharmacodynamic characteristics,exposure-response relationships,immunogenicity,medication in special populations,and the influence of intrinsic and extrinsic factors.It focuses on elaborating key issues such as PK optimization strategies,dosage regimen selection,and drug-drug interactions.The purpose of this article is to summarize the research priorities of clinical pharmacology for this class of drugs and provide a comprehensive overview for domestic research and development institutions.

Abstract:Objective:To evaluate the clinical efficacy and safety of Shugan Jianpi Yangxin Prescription in patients with insomnia disorder combining liver depression and spleen deficiency.Methods:This was a three-center,randomized,placebo controlled trial.A total of 130 patients of insomnia disorder with the Chinese medicine pattern of liver depression and spleen deficiency were enrolled and divided evenly into control and trial groups in this study.65 patients in trial group were treated with Shugan Jianpi Yangxin Prescription granules,and 65 patients in control group were treated with placebo granules of Shugan Jianpi Yangxin Prescription.All patients received a 4-week treatment course followed by a 4-week follow-up period.After 4 weeks of intervention,the changes in Pittsburgh Sleep Quality Index(PSQI)scores,Insomnia Severity Index(ISI)scores and Traditional Chinese Medicine(TCM)syndrome evaluation scale scores were analyzed between the two groups.Safety indicators was evaluated through vital signs,laboratory tests(blood routine,urine routine,liver/kidney function),and electrocardiogram results.Changes in ISI scores between the two groups were analyzed at weeks 6 and 8.Results:After 4 weeks'treatment,the total response rate was 93.85%in the trial group and 69.84%in the control group.There were significant differences between the trial and control groups in the following indexes:the PSQI scores,ISI scores,the TCM Syndrome Evaluation scale,and single symptoms of TCM syndromes including difficulty falling asleep,dream-disturbed sleep with easy awakening,low mood or irritability,and mental fatigue.Vital signs,laboratory parameters,and ECG results remained normal in both groups.No adverse reactions or adverse events were recorded.There were no adverse and serious adverse events during the treatment period in the trial and control group either.Conclusion:Shugan Jianpi Yangxin Prescription can significantly improve the clinical efficacy in patients with insomnia disorder combining liver depression and spleen deficiency.It had advantages in alleviating symptoms such as difficulty falling asleep,frequent nightmares or awakenings and the accompanying symptoms.

Abstract:Developing co-crystals is a technical approach to improve the solubility,stability,and solid-state characteristics of drugs,which shows significant value in drug development.Several co-crystal drugs have been marketed both domestically and internationally.However,regulatory frameworks for co-crystals differ between the U.S.Food and Drug Administration(FDA)and the European Medicines Agency(EMA).China currently lacks specific technical requirements for co-crystals.This paper references the current regulatory landscape for co-crystal drugs and combines insights from practical review work to discuss the pharmaceutical research of co-crystals from aspects including elucidation of structure,key physicochemical property studies,process development and control,and co-crystal quality studies.

Abstract:Therapeutic cancer vaccines represent a significant branch of cancer immunotherapy and have become a major focus of research and development in recent years.This article systematically reviews the latest progress in the development of therapeutic cancer vaccines,with a primary emphasis on comparing and analyzing the pharmaceutical properties of different technological platforms.It discusses the core considerations in pharmaceutical research,both general and platform-specific,and addresses the unique aspects of personalized therapeutic cancer vaccines.Furthermore,the article summarizes the key challenges these products facing and provides an outlook on future development directions.The aim is to offer valuable insights and references for the research,development,and regulatory submission of these innovative drugs.

Abstract:Neoantigen is a special tumor specific antigen produced by nonsynonymous gene mutations,gene rearrangements,and abnormal post-translational modifications in tumor cells.Because it is only expressed in tumor cells and has strong tumor cell targeting and immunogenicity,it is considered to be an ideal target for tumor immunotherapy.Neoantigen prediction algorithm based on artificial intelligence has its own particularity,and its accompanying regulatory issues have become the focus of attention in the field of international drug regulation.Based on the research progress in artificial intelligence in recent years,this paper systematically reviews the method evolution,existing challenges and future development trends of machine learning models and deep learning models for tumor neoantigen prediction,in order to provide insights for pharmaceutical research and regulation of neoantigen products.

Abstract:This paper focuses on the field of precision medicine,taking the invalidation request case of the invention patent titled"Use of Degarelix in the Preparation of a Medicament for Treating Metastatic Prostate Cancer",which was one of the top ten patent reexamination and invalidation cases of 2024,as a starting point.By combining classic cases from the European Patent Office and examination practices in China and Europe,this paper provides an in-depth analysis of the differences and evolving trends in the examination of invention patents related to patient-group-specific medical uses between China and Europe.The paper aims to provide insights for pharmaceutical R&D enterprises,patent practitioners,and relevant policy makers,thereby supporting the healthy development of patent innovation and protection in the pharmaceutical field.

Abstract:Perianal abscess and anal fistula are common conditions in anorectal surgery,often requiring surgical intervention.The postoperative recovery process significantly impacts patients'quality of life.In recent years,Compound Huangbai Liquid Liniment has garnered increasing attention and demonstrated certain efficacy in the preoperative and postoperative management of perianal abscess and anal fistula.However,there is currently a lack of unified guidelines or consensus to standardize its clinical application,including aspects such as indications,treatment duration,and dosage.This writing team reviewed relevant domestic and international guidelines and consensuses,summarized recent advances in clinical research,and employed a modified Delphi method to address key issues,including basic drug information,clinical questions,recommendations for clinical use,and considerations of safety.Finally,the nominal group technique was used at expert meetings to formulate recommendations and consensus statements.The aim is to clarify the advantages,dosage,treatment duration,efficacy,and safety of Compound Huangbai Liquid Liniment in the management of perianal abscess and anal fistula,thereby creating a guiding document to promote rational drug use,reduce medication risks,enhance clinical outcomes,and improve patient prognosis.

Abstract:Objective:To evaluate the efficacy and safety of Honghua Ruyi Wan(HHRYW)in patients with primary dysmenorrhea(PD).Methods:A multi-center,large-sample,self-controlled before-after clinical trial was designed.A total of 671 PD patients were enrolled to receive HHRYW treatment.The Visual Analogue Scale(VAS)score and COX menstrual symptom scale(CMSS)score were compared before and after the treatment.Results:In PD patients treated with HHRYW alone,both VAS and CMSS scores were significantly reduced compared to the baseline(P<0.0001).Within and between different treatment duration groups,there was statistically significant differences in VAS score improvement(P<0.0001).The severity and duration of PD-related symptoms were also significantly reduced post-treatment(P<0.0001).The improvement of VAS score in patients with cold coagulation and blood stasis type and Qi stagnation and blood stasis type was better than that in other syndrome types(P<0.000 1).Conclusion:HHRYW significantly alleviates pain severity(in patients with VAS scores≥4,indicating moderate-to-severe PD)and improves dysmenorrhea-related symptoms,especially for patients with cold coagulation and blood stasis type and Qi stagnation and blood stasis type.Its clinical application is worth promoting.

Abstract:Objective:To systematically review the effectiveness,safety,anti-tumor efficacy,and cost-effectiveness of trilaciclib in preventing chemotherapy-induced myelosuppression(CIM)in extensive stage small cell lung cancer(ES-SCLC),providing evidence-based support for rational drug use in clinical practice.Methods:Databases of PubMed,Embase,CENTRAL,CNKI,WangFang Data,and SinoMed were systematically searched.Randomized controlled trials(RCT)and economics research of preventing CIM with the use of trilaciclib or placebo prior to chemotherapy up to August 2024 were included.Reviewers screened literature according to the inclusion and exclusion criteria,extracted data,and assessed the risk bias of included studies.Then descriptive analysis or Meta-analysis was conducted using the RevMan 5.4 software.Results:A total of four RCTs involving 327 patients were included.Risk bias assessment results showed moderate bias.The Meta-analysis results showed that in terms of effectiveness,the incidence of severe neutropenia[RR=0.18,95%CI(0.05,0.63),P=0.008],neutropenia with fever[RR=0.27,95%CI(0.10,0.71),P=0.008],leukopenia[RR=0.34,95%CI(0.17,0.67),P=0.002],anemia[RR=0.68,95%CI(0.57,0.82),P<0.000 1]in the trilaciclib group were superior to the placebo group.The duration of severe neutropenia[MD=-3.23,95%CI(-4.38,-2.07),P<0.000 01]was shorter than the placebo group.The utilization rate of erythropoiesis-stimulating agent(ESA)[RR=0.49,95%CI(0.25,0.97),P=0.04]and the transfusion rate of red blood cells after 5 weeks of treatment[RR=0.59,95%CI(0.36,0.95),P=0.03]were significantly lower in the trilaciclib group.In terms of safety,there was no statistically significant difference in the incidence of all-cause mortality and different types of AEs between the two groups(P>0.05).In terms of anti-tumor efficacy,there was no significant difference in objective response rate,progression free survival,and overall survival between the two groups(P>0.05).In terms of economics,a total of four studies were included,and foreign data showed that trilaciclib was cost-effective.Conclusion:The use of trilaciclib before chemotherapy in ES-SCLC patients can effectively reduce the occurrence of CIM,reduce supportive treatments such as ESA and red blood cell transfusion,with good safety,no significant impact on survival,and can reduce the economic burden on patients.High quality research is still needed in the future to further evaluate the long-term survival outcomes.

Abstract:Coronary heart disease is a cardiovascular disease caused by atherosclerotic lesions in the coronary arteries,leading to vessel stenosis or occlusion,and subsequently resulting in myocardial ischemia,hypoxia or necrosis.It is also one of the most common cardiovascular diseases in clinical practice.In recent years,researches on the treatment of coronary heart disease with Codonopsis pilosula have gradually increased,demonstrating its unique advantages.Codonopsis pilosula exerts its effects through multiple mechanisms,including regulating the immune system,regulating lipid and blood pressure levels,improving left ventricular function,and inhibiting platelet aggregation.This article reviews the mechanisms of Codonopsis pilosula and its extracts in the treatment of coronary heart disease,providing a reference for the clinical development and application of Codonopsis pilosula as an alternative therapy for coronary heart disease.

Abstract: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.

Abstract: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 149661 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.

Abstract:Antitumor antibodies enhance the body's resistance to tumor cells by modulating the immune system or targeting molecules that are overexpressed on the surface of tumor cells,secreted into the extracellular space,and involved in tumor cell growth.These antibodies can directly inhibit or kill tumors,as well as deliver cytotoxic payloads to tumor cells in cancer treatment.With the development of biotechnology and pharmaceutical industry,antibody drugs have emerged as focal point in cancer treatment due to their unique advantages.They have become first-line treatment options for some types of tumors.Based on the patent information related to anti-tumor antibodies combined with the information of antibody drugs globally approved or under approval by World Health Organization-listed Authorities,this study conducts statistical analysis to study the overall situation of global and Chinese patent applications,technical distribution,valuable applicants and their related products.The essential patented technologies and research trending related to the core technical directions in the field of anti-tumor antibodies are discussed,including modifications of antibody constant region(Fc region),constructions of antibody drug conjugate and preparations of bispecific antibody.

Abstract:Objective:To explore the impact of artificial intelligence(AI)technology on innovation efficiency in the pharmaceutical manufacturing industry.Methods:Based on panel data from 26 provinces in China between 2012 and 2021,this study empirically examined the influence of AI technology on innovation efficiency in pharmaceutical manufacturing using data enveloping analysis,benchmark regression modeling and threshold effect modeling.Results:The benchmark regression results showed that the regression coefficients of AI technology on R&D efficiency and achievement conversion efficiency were 0.169 and 0.095,respectively.The threshold test results showed a double threshold effect for R&D efficiency and a single threshold effect for outcome transformation efficiency.Conclusion:AI technology significantly promoting effect on the innovation efficiency in the pharmaceutical manufacturing industry,with regional heterogeneity observed.In the era of the digital economy,a significant threshold effect exists between AI technology and pharmaceutical innovation efficiency.

Abstract:Clinical trials are the main procedure in the pre-market safety assessment of drugs,and quality management is carried out throughout the process.The quality of clinical trials is related to the safety and health of the medication population after drug marketing.As the main body to guarantee the quality of clinical trials and the rights and interests of the subjects,the vaccine trial research institutions should gradually establish and improve the quality assurance system of vaccine trials according to the latest laws,regulations,and guidelines,and combine the quality control of the process,to ensure the standardization of the trial process and the reliability of the results.This paper is based on a literature review and the work experience of vaccine trial research institutions in Guizhou Province,to share and discuss the quality management practice of institutions.

Abstract: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.

Abstract: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.

Abstract:This paper sorts out the phaseⅡclinical trials of traditional Chinese medicine registered in the drug clinical trial registration and information publicity platform of the Drug Evaluation Center of the State Drug Administration from January 1,2015 to October 1,2024,and analyzed the dosage form,indication,study design,sample size,dosage,and syndrome type,etc.A total of 393 Phase Ⅱ clinical trials involving 336 varieties were included in this study.The results showed that:granules have become the main dosage form in new drug development,followed by capsule and tablet.Three dosage forms accounted for 75.3%of the drugs.The indications included 136 diseases,with trials on the respiratory,digestive,and cardiovascular and cerebrovascular system registered the most.Most indications are represented by only one research variety each.More than 90%of the trials were randomized,double-blind,placebo-controlled designs.Dose exploration was conducted in 54.96%of the studies-primarily divided into two dosing groups-with a typical dose ratio being approximately 2∶1.The sample size of each trial ranged from 24 to 704 cases,and the average sample size of each group was 31 to 120 cases,accounting for 86.01%.Based on the analysis of the above information,this paper reviews the literature,compares the research characteristics of new Chinese medicine compound medicines approved for market from 2005 to 2021 and the review of application for registration of Chinese medicine from 2021 to 2024,and discusses the differences in research and development characteristics at different stages and the reasons,so as to provide beneficial inspiration for the research and development of new Chinese medicine medicines in the future.