The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

Sesquiterpenes are natural terpenes containing 15 carbon atoms. They are widely used in the perfume, pharmaceutical, and biofuel industries due to their remarkable biological activities. The traditional production of sesquiterpenes relies on chemical synthesis or plant extraction, which has the disadvantages of low yields and waste of resources. The construction of microbial cell factories for the efficient synthesis of sesquiterpenes by means of synthetic biology provides a new option. In recent years, with the development of metabolic engineering and synthetic biology, the heterologous synthesis of a variety of sesquiterpenes has been successfully achieved by metabolic engineering of the oleaginous yeast, Yarrowia lipolytica. In this paper, we review the research progress in the heterologous synthesis of different sesquiterpenes by Y. lipolytica, discuss the synthetic biology strategies commonly used in this field, and make an outlook on the research directions and engineering approaches to further enhance the sesquiterpene yield in this host. This paper provides a reference for strategies such as synergistic optimization of synthetic biology and metabolic engineering, enhanced precursors, and opens up new directions for the application of synthetic biology in green chemistry and sustainable production.
Yarrowia/genetics* ; Sesquiterpenes/metabolism* ; Metabolic Engineering/methods* ; Synthetic Biology/methods*

Objective:Systematic evaluation and integration of the real experience of dietary restriction in patients with inflammatory bowel disease, providing reference for the development of targeted intervention strategies.Methods:Qualitative studies on the dietary restriction experience of patients with inflammatory bowel disease retrieved from PubMed, Cochrane Library, Web of Science, Embase, CINAHL, China National Knowledge Infrastructure, Wanfang, VIP, and Chinese Biomedical Literature Database using computer search. The search period was from the establishment of the database to May 31, 2024. According to the Australian Joanna Briggs Institute Evidence Based Healthcare Center Qualitative Research Quality Evaluation Criteria, the quality of included literature was evaluated, and the results were subjected to meta-analysis using a pooled integration method.Results:A total of 9 studies were included, and 36 research results were extracted and summarized into 9 categories. Then, three integrated results were further synthesized, namely physical and mental impairment and social limitation; change attitude and actively explore; seeking external support to promote beneficial growth.Conclusions:Dietary restrictions for inflammatory bowel disease have various impacts on patients. Medical staff should focus on the nutritional status and emotional needs of patients, and provide multidimensional social support based on their actual dietary management experience. They should develop patient-centered personalized intervention measures to help patients achieve more scientific and effective dietary management and improve their overall quality of life.

Artificial intelligence(AI)has emerged as a cutting-edge technology leading the future and is a key engine for China's development.In the innovation and research of medical devices,AI has provided critical support in the areas of intelligent diagnostic assistance,intelligent therapeutic assis-tance,intelligent monitoring,life support,et al.Ma-chine learning-enabled device software functions(ML-DSFs)have become an essential component of many medical devices.Recently,the United States Food and Drug Administration(FDA)released a draft guidance titled"Marketing Submission Rec-ommendations for a Predetermined Change Con-trol Plan for Artificial Intelligence/Machine Learn-ing(AI/ML)-Enabled Device Software Functions(Draft)."that aimed to provide a forward-looking approach to foster the development of ML medical devices.By supporting iterative updates through modifications,this approach ensures the continu-ous safety and effectiveness of the devices.This guidance represents the latest in regulatory direc-tion and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI prod-ucts.Therefore,we plan to provide a detailed intro-duction and interpretation of the guidance,with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To investigate the trends of pathogen distribution and drug resistance in elderly patients with stroke-associated pneumonia(SAP)in China,providing references for clinical antibiotic selection and application.Methods:A meta-analysis was conducted to comprehensively evaluate changes in resistance rates of major pathogens isolated from elderly SAP patients to key clinical antibiotics over the past 10 years.The trends of antimicrobial resistance were analyzed.Results:A total of 12 qualified articles were screened out,involving 1 202 cases of pulmonary infections and 1 315 pathogenic isolates.Gram-negative bacilli accounted for 951 strains(72.32%),Gram-positive cocci for 278 strains(21.14%),and fungi for 86 strains(6.54%).The top five pathogens were Klebsiella pneumoniae,Pseudomonas aeruginosa,Acinetobacter Baumannii,Staphylococcus aureus and Escherichia coli.The resistance rates to various antibiotics showed minor fluctuations across years.Conclusions:Gram-negative bacilli dominate pulmonary infections in elderly stroke patients,with a high proportion of multidrug-resistant strains.Strengthened pathogen surveillance and rational antibiotic use are critical in clinical practice.

Objectives:The study assessed the relationship between atherogenic index of plasma(AIP)and the rapid progression of coronary non-target lesions.Methods:A total of 1 247 patients with coronary artery disease who underwent two coronary angiography examinations at Fuwai Hospital,Chinese Academy of Medical Sciences between January 2010 and September 2014 were enrolled in this retrospective study.The AIP is defined as the base 10 logarithm of the ratio of the concentrations of triglyceride to high-density lipoprotein cholesterol.Patients were divided into the high AIP group(n=623)and the low AIP group(n=624)based on the median value of AIP.Lesion rapid progression is defined as an increase of more than 10%in the lumen stenosis of the lesion with a stenosis rate of more than 50%,or an increase of more than 30%in the lumen stenosis rate of the lesion with a stenosis rate of less than 50%,or a progression to total occlusion within 2 years.Results:Median AIP was 0.39(0.23-0.56)in this patient cohort.Rapid progression of non-target lesions occurred in 65(5.21%),including 42(6.74%)in the high AIP group.The Kaplan-Meier curve showed that the cumulative incidence of rapid progression of non-target lesions was higher in the high AIP group than in the low AIP group(HR=1.751,95%CI:1.053-2.912,log-rank P=0.028).In univariate cox analysis,the AIP and high AIP correlated with rapid progression of non-target lesions.After multivariate adjustment,AIP was an independent risk factor for rapid progression of non-target lesions(adjusted HR=2.731,95%CI:1.090-6.844,P=0.032).Conclusions:AIP is an independent risk factor for rapid progression of non-target lesions.AIP should be considered as a biomarker for estimating the risk of cardiovascular disease,along with other traditional risk factors.

Objective:To investigate the impacts of nuclear receptor-interacting protein 1(NRIP1)on sepsis-evoked intesti-nal epithelial injury via transcriptional regulation of high mobility group box 1(HMGB1).Methods:The expression levels of NRIP1 and HMGB1 were detected by RT-qPCR and Western blot.The pathological changes of intestinal tissue were detected by HE staining.CCK-8 assay determined the optimal treatment time of LPS.Caco-2 cells were transfected with NRIP1 small interfering RNA(siRNA-NRIP1-1/2),and cell viability and apoptosis were detected by CCK-8 assay and flow cytometry,respectively.RT-qPCR and Western blot examined the expressions of inflammation-associated factors.Transepithelial resistance(TEER)was used to detect intestinal epi-thelial permeability.Western blot was used to detect the expressions of apoptosis and tight-junction related proteins.The binding rela-tionship between NRIP1 and HMGB1 was verified by luciferase reporting assay and chromatin immunoprecipitation assay(ChIP).After knocking down NRIP1 and overexpressing HMGB1 in LPS-treated Caco-2 cells,the functional experiment was performed again.Results:NRIP1 expression was fortified in the intestinal tissues of sepsis rats and LPS-treated Caco-2 cells.Interference with NRIP1 attenuated LPS-elicited Caco-2 cell viability injury,apoptosis,inflammatory response and barrier damage.Additionally,NRIP1 might activate HMGB1 expression at transcriptional level and HMGB1 elevation might reverse the impacts of NRIP1 absence on Caco-2 cell viability,apoptosis,inflammatory response as well as barrier function.Conclusion:NRIP1 may promote sepsis-elicited intestinal epi-thelial injury,which may be related to transcriptional activation of HMGB1.

This study constructed a porcine reproductive and respiratory syndrome virus(PRRSV)NADC30-like strain GP3 recombinant adenovirus vector vaccine through in vitro homologous re-combination to explore its immunological efficacy evaluation at the mouse level.Using type 5 ade-novirus as a vector,a recombinant adenovirus expressing PRRSV GP3 protein was prepared and i-dentified in vitro by fluorescence observation,PCR,and Western blot analysis.Immunize mice with recombinant adenovirus and detect humoral and cellular immune responses induced by recombi-nant adenovirus using indirect ELISA and ELISpot methods.The recombinant adenovirus rAdGP3 was identified by enzyme digestion,PCR,fluorescence and Western blot,indicating that the recom-binant adenovirus rAdGP3 was successfully constructed and packaged.After immunizing mice,spe-cific antibodies and neutralizing antibodies were produced,indicating that the recombinant adenovi-rus could elicit strong humoral immunity.ELISpot and lymphocyte proliferation assays showed that the recombinant adenovirus vaccine could stimulate the secretion of IFN-γ-specific T lymphocytes and induce the proliferation of lymphocytes,indicating that the recombinant adenovi-rus could enhance the level of cellular immune response.In this study,rAdGP3 recombinant adeno-virus was successfully constructed and had good immunogenicity at the mouse level,which provid-ed a reference for the development of novel PRRSV vaccines.