Aim This study aims to investigate the therapeutic effect and underlying mechanism of Todda-lia asiatica in the treatment of ischemic stroke(IS),utilizing network pharmacology,molecular docking technology,and animal experiments.Methods To screen the chemical components of Toddalia asiatica and its targets related to IS,a database was utilized.A protein-protein interaction(PPI)network was con-structed,followed by KEGG pathway enrichment anal-ysis.Molecular docking was performed to investigate the interaction between the components and target pro-teins.Finally,the effects of the drug on the PI3K/AKT/mTOR pathway and autophagy were validated through animal experiments.We established a middle cerebral artery occlusion(MCAO)rat model and di-vided the rats into the model group,Donepezil hydro-chloride group,Toddalia asiatica group,and sham op-eration group randomly.Observed the pathological changes in neurons of the rat hippocampal and cortical regions induced by the drug,performed immunohisto-chemical analysis to detect and localize mTOR expres-sion,and used Western blot to assess the expression levels of PI3K,p-PI3K,AKT,p-AKT,mTOR,as well as autophagy markers(LC3-Ⅱ and p62).Re-sults A total of 22 active ingredients from Toddalia asiatica,including AKT1 and MAPK3,were identified through screening.Additionally,194 signaling path-ways,such as PI3K/AKT and MAPK,were analyzed.The active compounds in Toddalia asiatica demonstra-ted stable binding affinity with targets associated with ischemic stroke.The results of the animal experiment indicated that,compared to the sham-operated group,the neuronal distribution in the hippocampal and corti-cal regions of the model group rats became sparser and more disorganized.There was a decrease in the number of Nissl bodies and cytoplasmic vacuolization.The ex-pression of mTOR-positive cells in the hippocampal and cortical regions was reduced.Additionally,the ex-pression levels of p-PI3K,p-AKT,mTOR,and p62 in the rat hippocampal tissue decreased(P＜0.05,P＜0.01),while the expression of LC3-Ⅱ increased(P＜0.01).Compared with the model group,the rats in the Toddalia asiatica and the Donepezil hydrochloride groups effectively improved the aforementioned indica-tors in rats.Conclusions Network pharmacology a-nalysis has revealed the promising potential of Toddalia asiatica in treating ischemic stroke,attributed to its di-verse components,targets,and pathways.The animal experiment showed that Toddalia asiatica can protect the neuronal structure in the hippocampal and cortical regions,which may be related to the inhibition of ex-cessive autophagy mediated by the PI3 K/AKT/mTOR pathway.

Oromucosal drug delivery preparations offer advantages such as convenient administration,suitability for patients with dysphagia,rapid onset of action,and avoidance of first-pass metabolism in the liver.The 2020 edition of the Chinese Pharmacopoeia,EP11.0,BP2022,USP44-NF39,and JP18 all include relevant standards for the quality control of different oromucosal drug delivery systems.This article compares the differences in general re-quirements for oromucosal formulations among different countries and provides an overview of inspection items for marketed oral mucosal formulations and those documented in pharmacopoeias both domestically and internationally.Foreign pharmacopoeias include a wide range of oromucosal drug delivery formulations,with more refined quality control measures for systemic action.These findings can serve as a reference for the improvement and enhancement of standards for oromucosal drug delivery systems in China.

Objective:To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia,and to strengthen understanding of the disease.Methods:7 cases of acute leukemia(AL)patients diagnosed with mucormycosis by metagenomic next generation sequencing(mNGS)after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected,and their clinical data,including clinical characteristics,diagnosis,treatment,and prognosis,were retrospectively analyzed.Results:Among the 7 patients with AL complicated with mucormycosis,there were 3 males and 4 females,with a median age of 52(20-59)years.There were 6 cases of acute myeloid leukemia(AML)and 1 case of acute lymphocytic leukemia(ALL).Extrapulmonary involvement in 4 cases,including 1 case suspected of central nervous system involvement.The median time for the occurrence of mucor infection was 16(6-69)days after chemotherapy and 19(14-154)days after agranulocytosis.The main clinical manifestations of mucormycosis were fever(7/7),cough(3/7),chest pain(3/7)and dyspnea(1/7).The most common chest CT imaging findings were nodules,patchy or mass consolidation(6/7).All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase.5 patients died within 8 months,and the median time from diagnosis to death was 1 month.Conclusion:Although prophylactic antifungal therapy is adopted,patients with acute leukemia still have a risk of mucor infection during the neutropenia phase.Fever is the main manifestation in the early stage of mucor infection.The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.

Objective To quantitatively analyze the impact of environmental hygiene on the occurrence of health-care-associated infections(HAI).Methods Monitoring data of HAI and environmental hygiene from a tertiary first-class hospital from January 2018 to December 2022 were collected,and the impact of environmental bacterial colony forming unit(CFU)on the occurrence of HAI was analyzed by a time-series generalized additive model.Results The single-contamination model showed a significant positive correlation between HAI and staff's hand bacterial CFU(β1=0.009,P=0.012).For an increase of 1 interquartile range(IQR)in the monthly mean CFU per dish(MCFU/Dish)of staffs'hand,the incidence of HAI increased by 13.28％(95％CI:2.82％-24.81％).Subgroup and lag effect analysis showed that when the monthly MCFU/Dish(after hand disinfection)of staffs'hand in-creased by one IQR,the excess risk(ER)of HAI for the month(lag0)was 16.26％(95％CI:15.45％-17.09％).In the multi-contamination model,the correlation between surface contamination and HAI was also statistically sig-nificant.Conclusion There is a significant correlation between hospital environmental hygiene and the occurrence of HAI.

Hospital water supply system may serve as a reservoir of waterborne pathogens,and contaminated wa-ter can lead to the occurrence and outbreak of healthcare-associated infection(HAI),which bring great challenge to the prevention and control of HAI.Waterborne pathogens,such as Pseudomonas aeruginosa,Legionella,no-tu-berculous Mycobacterium,Acinetobacter,and Stenotrophomonas maltophilia,often propagate and spread through the water supply system.Water temperature,residual chlorine concentration,and biofilm in water supply system are key influencing factors.This article reviews the current situation of waterborne infection,characteristics and in-fluencing factors of water supply system in medical institutions in recent years,as well as related waterborne infec-tion events at home and abroad,so as to bring new insights for the prevention and control of waterborne infection in medical institutions.

Objective:To analyze clinical significance of peripheral blood neutrophil CD64(nCD64)index in patients with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods:The clinical data of 98 AAV patients admitted to the First Medical Center of Chinese People's Liberation Army General Hospital from February 1,2023 to February 29,2024 were retrospectively selected,and they were divided into the high-value group(nCD64 index＞1.82,28 patients)and the normal-value group(nCD64 index≤1.82,70 patients)based on the nCD64 index.Ethylenediaminetetraacetic acid(EDTA)-anticoagulated venous blood specimens were collected from patients in both groups,and the mean fluorescence intensity of CD64 expression on the surfaces of polymorphonuclear leukocytes(PMN),lymphocytes(Lym)and monocytes(Mo)was detected by flow cytometry.Clinical manifestations,relevant examination data of hospital,and survival situation of patients with regular follow-up were compared between the two groups.Results:Spearman correlation analysis showed that peripheral blood nCD64 index was positively correlated with Birmingham vasculitis activity score(BVAS)in AAV patients(r=0.216,P＜0.05).There were no statistically significant differences in white blood cells(109/L),blood creatinine(μmol/L),CD8+lymphocytes(amount/μl),CD3-CD16+CD56+lymphocytes(amount/μl),blood sedimentation and interleukin 6 between the two groups.The mean values of BVAS,neutrophils(109/L),CD8+CD28-lymphocytes(％)were respectively(14.96±8.62),(7.51±4.56),(22.16±13.28)in high-value group,which were significantly higher than those[(11.88±7.39),(6.32±3.60)and(17.32±11.27)]in normal-value group,and the mean values of lymphocytes(109/L),platelets(109/L),hemoglobin(g/L),CD3+lymphocytes(amount/Al),CD4+lymphocytes(amount/μl),CD8+CD28+lymphocytes(％)were respectively(1.52±1.01),(216.84±92.32),(106.26±21.99),(1401.15±658.22),(618.43±420.50)and(12.43±5.98)in high-value group,which were significantly lower than those[(1.98±0.95),(248.20±97.21),(114.30±24.71),(1815.43±657.29),(969.15±385.72)and(15.77±7.66)]in normal-value group,and the differences of them between two groups were statistically significant(t=-2.68,-2.04,-2.54,3.25,2.26,2.34,2.02,2.84,3.02,P＜0.05),respectively.Neutrophil/lymphocyte ratio and C-reactive protein of high-value group were higher than those of normal-value group,and eosinophils of high-value group were lower than that of normal-value group,and the differences of them between two groups were statistically significant(Z=-3.370,-2.396,-4.462,P＜0.05),respectively.Conclusions:Peripheral blood nCD64 index is positively correlated with BVAS in AAV patients,which involve in multiple immune cells and inflammatory factors.It has clinically application value in monitoring the disease progression and assessing the prognosis.

Type 1 diabetes mellitus is a T-cell-mediated autoimmune disease that commonly affects adolescents, characterized by progressive destruction of pancreatic β-cells, absolute insulin deficiency, and hyperglycemia. The pathogenesis of type 1 diabetes mellitus is complex and is believed to be mainly associated with immunity, environment, and genetics. There is increasing evidence that gut microbiota is closely related to the occurrence of type 1 diabetes mellitus. This article focuses on the immune mechanisms and roles of gut microbiota and its derivatives in the development of type 1 diabetes mellitus from the perspectives of innate and adaptive immunity. Additionally, it introduces therapeutic approaches targeting gut microbiota for the treatment of type 1 diabetes mellitus.

Objective To investigate the effect of Ganoderma lucidum polysaccharide peptide(GLPP)on proliferation,migration and apoptosis of diffuse large B cell lymphoma(DLBCL)cells and its mechanism.Methods OCI-LY19 cells were divided into six groups:control,GLPP,si-NC,si-protein arginine methyltransferase 6(PRMT6),GLPP+pcDNA3.1-NC and GLPP+pcDNA3.1-PRMT6 groups.The si-NC,si-PRMT6,GLPP+pcDNA3.1-NC and GLPP+pcDNA3.1-PRMT6 groups were transfected with si-NC,si-PRMT6,pcDNA3.1-NC and pcDNA3.1-PRMT6,respectively.After the transfection was completed,control,si-NC and si-PRMT6 groups were treated with RPMI-1640 medium,while the GLPP,GLPP+pcDNA3.1-NC and GLPP+pcDNA3.1-PRMT6 groups were cultured with RPMI-1640 medium containing with 20 μg·mL-1 GLPP.After administration 24 h,the cell proliferation inhibition rates,mobility rates and apoptosis rates were detected.The expression levels of PRMT6 protein were measured by Western blotting.Results The cell proliferation inhibition rates of si-NC,si-PRMT6,GLPP+pcDNA3.1-NC and GLPP+pcDNA3.1-PRMT6 groups were(1.28±0.16)％,(38.61±3.29)％,(52.84±7.74)％and(22.75±3.87)％,respectively.The number of cell migrations in the control,GLPP,si-NC,si-PRMT6,GLPP+pcDNA3.1-NC and GLPP+pcDNA3.1-PRMT6 groups was(252.65±24.65),(136.54±16.46),(231.65±21.24),(142.76±15.34),(140.23±9.84)and(192.38±23.38)cells;the apoptosis rates were(4.36±0.52)％,(28.24±2.36)％,(4.23±0.45)％,(24.54±2.27)％,(28.42±3.85)％and(14.25±2.13)％);the expression levels of PRMT6 protein were 1.82±0.21,0.56±0.05,1.78±0.19,0.54±0.05,0.29±0.02 and 0.32±0.03,respectively.The differences of above indexes were statistically significant between control group and GLPP group,between si-NC group and si-PRMT6 group,between GLPP+pcDNA3.1-NC group and GLPP+pcDNA3.1-PRMT6 group(all P＜0.05).Conclusion GLPP could inhibit proliferation,migration and promote apoptosis of DLBCL cells by down-regulating PRMT6 expression.

Polycystic ovary syndrome(PCOS)is a common endocrine and metabolic disease in gynecology.The main clinical manifestations are infertility,hirsuty,obesity,menstrual disorders,etc.,which seriously affect women's health.Studies have shown that the mechanism of action of traditional Chinese medicine in the treatment of PCOS involves a variety of signaling pathways,among which advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway is an important pathway regulating inflammation and oxidative stress.More and more Chinese herbal compounds,single herbs and their extracts can reduce inflammation,oxidative stress,insulin resistance and hyperandrogenemia in patients by regulating AGE-RAGE signaling pathway,which provides a new strategy and direction for the treatment of PCOS.However,there is currently no comprehensive summary of Chinese medicine intervention in the treatment of PCOS by AGE-RAGE signaling pathway.Therefore,this paper reviews the current research status of Chinese medicine regulation of AGE-RAGE signaling pathway in the treatment of PCOS in recent years,so as to provide new directions and thoughts for further research on PCOS.

Objective To observe the effects of indobufen tablets combined with clopidogrel tablets on levels of serum myocardial injury indexes and incidence of major adverse cardiovascular events(MACE)in elderly patients with coronary heart disease after percutaneous coronary intervention(PCI).Methods The elderly patients with coronary heart disease after PCI were divided into treatment group[clopidogrel 75 mg(qd)combined with indobufen 200 mg(qd)]and control group[clopidogrel 75 mg(qd)combined with aspirin 100 mg(qd)]according to cohort method.All patients were treated for 3 months.The total effective rate,serum myocardial injury indexes[N terminal pro B type natriuretic peptide(NT-proBNP),cardiac troponin Ⅰ(cTn Ⅰ)],coagulation-fibrinolysis indexes[fibrinogen(FIB),prothrombin time(PT),antithrombin Ⅲ(AT-Ⅲ)]and platelet function indexes[platelet distribution width(PDW)]were compared between two groups.Occurrence of bleeding events and MACE within 6 months were compared between the two groups.The safety was evaluated.Results There were 32 cases in control group and 32 cases in treatment group.After treatment,the total effective rates in treatment group and control group were 93.75％(30 cases/32 cases)and 78.13％(25 cases/32 cases),without significant difference(P＞0.05).After treatment,NT-proBNP levels in treatment group and control group were(202.65±30.77)and(283.52±31.42)pg·mL-1,cTn Ⅰ levels were(0.06±0.01)and(0.12±0.03)ng·mL-1,FIB levels were(3.17±0.51)and(3.84±0.59)g·L-1,PT were(15.87±1.23)and(14.92±1.35)s,AT-Ⅲ levels were(138.95±14.18)％and(125.17±14.96)％,PDW were(17.04±2.04)％and(19.13±2.32)％,the differences were statistically significant(all P＜0.05).The incidences of bleeding events in treatment group and control group were 6.25％and 15.63％,adverse drug reactions were 9.38％and 15.63％,respectively,the differences of above indexes were statistically significant between two groups(all P＞0.05).The total incidences of MACE in treatment group and control group were 6.25％and 25.00％,respectively(P＜0.05).Conclusion Indobufen tablets combined with clopidogrel tablets can reduce levels of serum myocardial injury indexes in elderly patients with coronary heart disease after PCI,improve coagulation-fibrinolysis function and reduce the incidence of MACE.