ObjectiveTo explore the mechanisms of Yangjing Tongluo prescription （YJTL） in the treatment of intrauterine adhesion （IUA） from the perspective of oxidative stress mediated by the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Keap1/Nrf2/HO-1） signaling pathway. MethodsA total of 48 rats with normal estrous cycles were selected and randomly divided into a normal group （n=8） and a modeling group （n=40）. An IUA rat model was established using a dual-injury method combining surgical curettage and infection. Eight rats were randomly selected from the modeling group for a pilot experiment to confirm successful model establishment. After successful modeling， the remaining 32 rats were randomly divided into a model group， a low-dose YJTL group （YJTL-L）， a high-dose YJTL group （YJTL-H）， and a Progynova group. Rats in the normal and model groups were administered purified water （15 mL·kg^-1） by gavage daily， while rats in the YJTL-L， YJTL-H， and Progynova groups received YJTL at doses of 6.43 and 12.86 g·kg^-1 and Progynova at 2.06 × 10^-4 g·kg^-1， respectively， for 14 consecutive days. The general condition， uterine morphology， and uterine index of the rats were monitored. Histopathological changes in uterine tissue were observed using hematoxylin-eosin （HE） staining. Serum levels of reactive oxygen species （ROS） and glutathione peroxidase （GSH-Px） were measured by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of Keap1， Nrf2， and HO-1 in endometrial tissue were detected by Western blot. Immunofluorescence （IF） was used to assess the distribution of Nrf2 and HO-1， as well as the expression of Nrf2 in the cytoplasm and nucleus. ResultsCompared with the normal group， rats in the model group exhibited poor mental status and reduced mobility， markedly edematous and tortuous uterine morphology， decreased gland number， and inflammatory reactions in the endometrium， along with an increased uterine organ index （P<0.05）. Serum ROS levels were significantly increased （P<0.05）， while serum GSH-Px levels were significantly decreased （P<0.05）. In endometrial tissue， Keap1 protein expression was increased （P<0.05）， whereas Nrf2 and HO-1 protein expression was decreased. Mild nuclear translocation of Nrf2 was observed， accompanied by increased relative fluorescence intensity of nuclear Nrf2 and decreased relative fluorescence intensity of cytoplasmic HO-1. Compared with the model group， all treatment groups showed varying degrees of improvement in the above symptoms and pathological changes. Serum ROS levels were reduced （P<0.05）， serum GSH-Px levels were increased （P<0.05）， Keap1 protein expression in endometrial tissue was decreased， and Nrf2 and HO-1 protein expression was increased in a dose-dependent manner （P<0.05）. Notably， significant nuclear translocation of Nrf2 was observed， with correspondingly increased relative fluorescence intensity of nuclear Nrf2 and enhanced relative fluorescence intensity of cytoplasmic HO-1. ConclusionYJTL may enhance antioxidant capacity and repair oxidative damage to the endometrial basal layer by regulating the Keap1/Nrf2/HO-1 signaling pathway.

[摘 要] 目的：探讨绿茶单体表没食子儿茶素没食子酸酯（EGCG）对大鼠肝癌发生过程中肠道菌群结构变化的影响。方法：建立二乙基亚硝胺（DEN）诱导的肝癌大鼠模型。将26只SD大鼠随机分成3组，分别为正常对照组、肝癌组和EGCG干预组。从实验开始第1天起，EGCG干预组每日给予EGCG（40 mg/kg）灌胃，正常对照组和肝癌组给予等量生理盐水灌胃，1次/日，持续至第20周。灌胃结束后，采集大鼠粪便样本，提取DNA，进行高通量16S rRNA V3-V4区测序；处死大鼠，取肝，观察肿瘤形成情况，并计算肝癌发生率。对测序数据进行生物信息学分析：经质控、聚类获得操作分类单元（OTU）表，据此计算α多样性指数（包括Observed species、Chao1、Shannon和Simpson指数），并进行β多样性分析。同时，对物种进行分类学注释，比较各组间菌群组成与丰度差异。结果： EGCG干预组大鼠（8只）肝脏肿瘤形成率明显低于肝癌组（10只）（50% vs 100%， P = 0.023），正常对照组（8只）大鼠无肿瘤发生。在肠道菌群方面，肝癌组操作分类单元（OTU）数量远低于正常对照组（P <0.001），而EGCG干预组OTU数量总体上高于肝癌组（P = 0.021）。α多样性分析显示，肝癌组Shannon指数低于正常对照组（P < 0.05）；此外，与肝癌组相比，EGCG干预组的Observed species指数、Chao1指数、Shannon指数和Simpson指数均显著提高（P < 0.05）。β多样性分析及主坐标分析（PCoA）表明，三组肠道菌群结构存在显著分离（PERMANOVA， R² = 0.3918， P = 0.001），其中EGCG干预组群落结构介于肝癌组与正常对照组之间，并更接近于正常对照组。肝癌组大鼠较正常大鼠肠道菌群中链球菌等潜在致病菌富集，丁酸产生相关菌（如丁酸球菌属、瘤胃球菌属等）丰度显著降低（P < 0.05）。相比之下，在EGCG干预肝癌发生过程中，大鼠肠道菌群结构相对稳定。厚壁菌门/拟杆菌门比值较肝癌组显著提高（P < 0.05），益生菌（如双歧杆菌属、乳杆菌属等）和丁酸产生相关菌（如丁酸球菌属）富集。结论：EGCG干预可降低DEN诱导的大鼠肝癌发生率，并有助于稳定肠道菌群结构，其作用可能与增加菌群多样性、促进益生菌及丁酸产生菌富集、恢复菌群平衡有关。

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

Objective:To characterize the epidemiology of respiratory syndrome across healthcare facilities of different types and tiers in Beijing City, to compare pathogen-testing modalities and their associations with adverse outcomes, and to identify key factors associated with progression to severe illness, thereby informing regional prevention, control, and clinical optimization.Methods:The multicenter observational cohort study was performed using outpatient and emergency department data from five sentinel hospitals in Beijing (Beijing Xiaotangshan Hospital, Beijing Chaoyang District Shuangqiao Hospital, Beijing Haidian Hospital, Beijing You′an Hospital, Capital Medical University (Beijing You′an Hospital), and Beijing Ditan Hospital, Capital Medical University (Beijing Ditan Hospital)) from October 1st, 2023 to April 9th, 2025. Dual-target (two-plex) and triple-target (three-plex) respiratory specimens were collected. Demographic characteristics, visit information, pathogen-testing modalities and results were collected, and the epidemiologic features of patients who progressed to severe illness between the influenza high-incidence season (December to May) and the non-influenza season (June to November) were compared. Categorical variables were analyzed using the chi-square test. Multivariable logistic regression was used to estimate associations between covariates and risk of progression to severe illness.Results:Among the 192 131 cases, patients visited at Beijing You′an Hospital were concentrated in the 16 to 44 year age group, accounting for 66.79%(32 532/48 708). Beijing Xiaotangshan Hospital had a broad age distribution, with older adults comprising up to 22.35% (885/3 960). Of the 47 349 respiratory specimens across the five hospitals, Beijing You′an Hospital had the highest positivity rate for dual-target testing (46.76%(1 585/3 390)), while Beijing Haidian Hospital conducted the largest number of this tests ( n=12 514). For triple-target testing, Beijing You′an Hospital again had the highest positivity rate (45.03%(2 835/6 296)), whereas Beijing Ditan Hospital tested the most specimens ( n=12 011; positivity rate was 29.73%(3 571/12 011)). The influenza season within the same period (November 2023 to January 2024) exhibited a bimodal pattern, with alternating circulation of influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among 32 744 outpatients/emergency patients who progressed to severe illness, significant seasonal differences were observed by sex, age, comorbidity status, and infection type ( χ2=6.60, 189.24, 32.71 and 189.99, respectively; all P<0.05). After adjustment for sex, age group, comorbidities, and infection type, testing modality remained significantly associated with risk of progression (dual-target testing, odds ratio ( OR)=0.116, 95% confidence interval ( CI) 0.111 to 0.122, P<0.001); no testing, OR=0.063, 95% CI 0.060 to 0.065, P<0.001). Conclusions:The epidemiological pattern of respiratory pathogens undergo significant changes after October 2023, which is characterized by alternating waves of influenza viruses and SARS-CoV-2 with pronounced seasonality and diversity. Substantial inter-hospital differences are observed in testing modalities and positivity rates. Risk of progression to severe illness varies significantly by sex, age, comorbidity burden, and infection type, and is closely associated with the testing modality. These findings support strengthening multiplex pathogen testing and targeted surveillance of high-risk groups to improve early identification and precise control of febrile-respiratory syndromes.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Objective With the increasing demand from the country for optimizing the allocation of medical resources and improving service balance,this study aims to promote the improvement of regional medical service levels through the explora-tion and practice of the management model of provincial medical quality control centers.Methods The First Affiliated Hospital of Sun Yat-sen University,as the affiliated unit of one of the 14 provincial quality control centers,organizes the quality control center to play a professional role and improve its management efficiency through stable construction,solid framework,reorgani-zation,and multiple support.Results With the leadership and support of the health administrative department in Guangdong Province,the hospital has organized the provincial quality control center to carry out its work in an orderly manner,promoting the continuous improvement of the comprehensive strength of regional medical services and key indicators of various professional qual-ity control centers.Conclusion The management model of the quality control center in this study has shown initial effectiveness.

Diamond-Blackfan anemia(DBA),also known as congenital pure red cell aplasia,is a rare genetic disorder characterized by bone marrow failure,congenital anomalies,and severe red blood cell abnormalities.The rarity of the condition,and consequently limited patient pool and scarcity of research models,means that the pathogenic mechanisms associated with genetic mutations in DBA remain uncertain,and the clinical treatment options are limited.This review synthesizes the findings from zebrafish,mouse,and human cellular models of DBA mutations.We clarify the pathogenic mechanisms and monitor the progression of drugs into clinical trials,thereby aiding further in-depth explorations into the etiology and therapeutic advancements for DBA.

Nitric oxide synthase(NOS)and its product nitric oxide are involved in learning and memory functions.Increasing evidence shows that NOS plays an important role in the pathogenesis of Alzheimer's disease,influencing β-amyloid protein(Aβ)deposition,neuroinflammation,oxidative stress,abnormal microglia activation,synapse damage,autophagy,abnormal mitochondrial function of nerve cells,and cerebral hypoperfusion or vascular endothelial cell injury.This review summarizes the recent evidence for the role of NOS in the pathogenesis of Alzheimer's disease and provides new feasible targets for the prevention and treatment of Alzheimer's disease.