With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

BACKGROUND:At present,the pathogenesis of osteoarthritis is still unclear,and there is a lack of effective means to control the disease.Research on osteoarthritis is mostly concentrated in the field of immunity,and there are few studies in the field of oxidative stress. OBJECTIVE:To explore the roles of oxidative stress and immune infiltration in osteoarthritis and to predict related miRNAs and therapeutic agents. METHODS:The GSE55235 dataset(10 samples of osteoarthritis and 10 healthy control samples)and the GSE55457 dataset(10 samples of osteoarthritis and 10 healthy control samples)were obtained from the GEO database for merging to obtain their differentially expressed genes that were combined with oxidative stress genes to get the differentially expressed genes of oxidative stress.The differentially expressed genes of oxidative stress were analyzed for KEGG and GO enrichment,and the osteoarthritis pathways and biological processes were evaluated using GSEA enrichment analysis.The protein-protein interaction network was constructed using the STRING online website and Cytoscape software,and the Degree algorithm was run to get the key genes.The GSE1919 dataset was obtained from the GEO database as a validation dataset,and the key genes were analyzed by variance analysis and receiver operating characteristic curve analysis to get the core genes.In addition,immune infiltration was evaluated by CIBERSORT and the correlation between core genes and immune cells was explored.miRNA prediction of core genes was performed using TargetScan and target drugs were predicted using the DSigDB database. RESULTS AND CONCLUSION:Sixty-five differentially expressed genes and five core genes(IL1B,CXCL8,MYC,NFKBIA,JUN)associated with oxidative stress were identified.Enrichment analysis showed that differentially expressed genes associated with oxidative stress were concentrated in the pathways of oxidative stress,interleukin-17,osteoclast differentiation,fluid shear stress and atherosclerosis.The area under the receiver operating characteristic curve for the five core genes exceeded 0.85,indicating their excellent specificity and sensitivity in diagnosing bone and joint conditions,as well as their close association with immune cells.The predicted miRNA was has-miR-3937,and the therapeutic small-molecule drugs were metformin,ionomycin and celecoxib.To conclude,oxidative stress and immune infiltration exist in osteoarthritis,and immune infiltration is involved in activating oxidative stress.The core genes and predicted miRNAs can be used as novel markers for the diagnosis of osteoarthritis,and small molecule drugs are predicted to treat osteoarthritis.

Objective To develop the functions and optimize the automatic monitoring module for arrhythmias of the adverse drug event active surveillance and assessment system-Ⅱ,in order to continuously improve the performance,enhance the monitoring efficiency,and explore the ways to optimize the module.Methods Expand and optimize the functions of the module,increase the customized configuration,and determine the optimal setting conditions;compare the optimized test data with the results of the evaluation studies on the automatic monitoring of drug-induced arrhythmias in large samples of medicated population previously,and verify the optimization extent as well as the accuracy of the module.Results In the new module optimized according to the characteristics of the monitoring population,the function of"mandatory medical order keywords"was added,and it was determined that the inclusion of 6 electrocardiogram examination-related medical order keywords with a frequency of not less than 2 occurrences was the optimal configuration condition for the optimization of the module;combining the results of the previous automatic monitoring and evaluation researches,the system functions were verified and compared under the conditions of using the whole drugs and 2 kinds of single drug.While there was no loss of true positive cases,the number of cases with system alarms decreased by 30.75％,80.13％and 90.82％,respectively,compared with that before the optimization of the module,and the positive predictive value was significantly improved.Conclusion After the function expansion and optimization,the automatic monitoring module of drug-induced arrhythmias significantly reduces the labor cost of case evaluation and keeps the accuracy of monitoring results constant;the new module can better adapt to the demands of different automatic monitoring modes and operates stably,which is more generalizable and flexible,and provides a new way of considering for the research and development of automatic monitoring modules.

Objective To obtain the occurrence and clinical characteristics of central nervous system adverse drug reactions(CNS-ADR)associated with three kinds of carbapenems,and to provide reference for clinical drug safety.Methods Based on adverse drug event active surveillance and assessment system-Ⅱ(ADE-ASAS-Ⅱ),retrospective automated monitoring of inpatients using imipenem,meropenem,and biapenem in a tertiary hospital from January 2022 to December 2022 was conducted.The incidence of carbapenem related CNS-ADR was calculated,and the basic conditions,disease conditions,drug use,occurrence time of ADR and symptoms of patients with CNS-ADR were analyzed by descriptive statistics.Results A total of 2 482 patients with 2 709 times of medication were included in this study,and a total of 93 positive cases of CNS-ADR occurred,with an overall incidence of 3.43％for all three medications,3.98％for imipenem,3.51％for meropenem,and 2.78％for biapenem.The indications for the 93 positive cases of CNS-ADR were mainly pulmonary infections(59.13％)and abdominal infections(25.80％);they occurred mostly within 7 days of the administration of the medication;with a variety of clinical manifestations,with anxiety/irritability being the most common,and epilepsy appearing most frequently in severe cases.Co-administration of proton pump inhibitors and cephalosporins accounted for a greater proportion of positive cases,50.54％of positive cases had a history of surgery,and 69.89％of positive cases were associated with electrolyte disturbances.Conclusion Clinical use of carbapenems should be based on the actual situation of the patient to develop an individualised drug regimen,and special attention should be paid to patients with comorbidities of renal disease,electrolyte disorders,and a history of previous surgery and neurological disorders,in order to reduce the risk of the occurrence of CNS-ADR.

Objective: To understand the current situation and differences in physical activity among children and adolescents in different regions of China, so as to provide a scientific reference for promoting the level of overall physical activity promotion among children and adolescents in China. Methods: From June to December 2023, the student satisfaction assessment questionnaire for the national children and adolescents theme fitness activity "Run, Youth!" was conducted, which was administered via a combined online and offline questionnaire survey to explore 397 013 students participation in the "Run, Youth!" activity in 2023. Descriptive statistics, Logistic regression, and other approaches were utilized for data analysis. Results: There were notable disparities in the rates of children and adolescents meeting the physical activity standards among northeast China, northwest China, north China, east China, central China and southwest China (10.27%, 11.79%, 9.32%, 8.48%, 8.81%, 7.30%) ( χ 2=33.48, P <0.05). The results of multivariate Logistic regression analysis showed that rate of recommended level of physical activity among children in northwest China, boys, children aged 16-18, children in urban areas were relatively high ( OR =1.12, 1.68, 0.60, 1.88, P < 0.05 ). After adjusting for confounding factors, the results of binary Logistic regression analysis showed that there was an interactive effect relationship between the interaction of region, age, gender, and urban-rural distribution and physical activity among children and adolescents ( OR=0.51, P <0.01). Based on gender analysis, weekly physical activity duration of boys in each region surpassed that of girls; based on age analysis, except for the central and southwestern regions, weekly physical activity duration of children and adolescents gradually increased with age in other regions; based on the proportion of urban and rural areas, weekly physical activity duration of children and adolescents in urban areas across all regions exceeded that in rural areas. Conclusions The attainment rate of sufficient physical activity among children and adolescents in northwest China is the highest, and the differences between regions are not significant. The participation and level of physical activity of male students in each region surpass those of females and the attainment rate of physical activity of physical activity of urban children and adolescents is higher than that of those in rural areas.

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Objective To understand the incidence and characteristics of adverse drug reactions(ADRs)of carbapenems,explore the relevant risk signals,and provide a reference for clinically safe drug use.Methods All spontaneous reports of carbapenem drug-related ADRs from January 2008 to October 2022 in the Adverse Drug Reaction Monitoring Center,PLA General Hospital's ADR database were retrieved,and information such as patients'general conditions,involved systems and organs damage,and the names of ADRs involved were retrospectively analysed.Using the reporting odd ratio method,the proportional reporting ratio method,the Medicines and Healthcare Products Regulatory Agency method,and information component method to obtain risk signals of carbapenem antimicrobial drug-related ADR.Results A total of 2 642 ADR reports of carbapenems were reported,of which 410 serious ADR reports(15.52％)were serious ADR reports,five cabapenem antimirobial drug species were mainly involved.In descending order of composition were imipenem cilastatin(51.28％),meropenem(32.13％),biapenem(8.10％),ertapenem(7.68％),and panipenem(0.79％).The male to female ratio of patients was 1.74:1,with the most age＞60 years(59.69％).A total of 14"drug-ADR name"combinations generated risk signals in all four data mining methods,with meropenem being the most signals,and imipenem cilastatin and ertapenem had a high number of reported ADR in nervous system.Conclusion The results of risk signal mining are basically consistent with the known carbapenem ADR information,during the use of carbapenem antimicrobial drugs in the clinic,it is recommended to monitor patients'liver and kidney functions as well as blood biochemical indexes,so as to strengthen the awareness of vigilance in the clinical use of carbapenem antimicrobial drugs,and timely recognize and deal with ADRs in a timely manner,and to avoid the occurrence of serious ADRs.

Objective To construct a module for drug-induced central nervous system adverse reactions(CNS-ADR)within the Clinical Adverse Drug Event Active Monitoring and Intelligent Assessment Alert System-Ⅱ(ADE-ASAS-Ⅱ),and to conduct a large-scale,real-world active monitoring and evaluation of CNS-ADR specifically related to imipenem/cilastatin.Methods Based on literature review,spontaneous report evaluation,and initial word set of CNS-ADR related descriptions in electronic medical records,text recognition technology was used to construct and optimize the condition settings of the CNS-ADR automatic monitoring module.Hospitalized patients using imipenem/cilastatin were retrospectively monitored from 2017 to 2021,and the positive patients which had CNS-ADR were statistically described in terms of the demographic characteristics,CNS symptoms,and hospital departments.Results Based on a repeated testing optimization using 1 185 manually monitored results,the best setting for the determined module includes 62 sets of keywords,with a positive predictive value(PPV)of 13.63％and a recall rate of 100％.Expanding the monitoring to 8 222 medication users using this module,281 cases of positive causality were identified,with an incidence rate of 3.42％.Among them,patients over 60 years old accounted for 50.17％,and the main manifestations of CNS-ADR were epileptic seizures,headaches,mania,and delirium.Conclusion The CNS-ADR automatic monitoring module established based on ADE-ASAS-Ⅱ provides fast and reliable text data mining support for conducting real-world research on CNS-ADR.

Professor ZHOU Peng has deeply discussed the pathological characteristics of psoriasis vulgaris,emphasizing that the disease is usually manifested deficiency interweaved with excess,leading to frequent recurrence and persistent refractory,which may lead to psychological and emotional problems of patients.This paper further expounds the effect of blood stasis on the pathogenesis,progression and prognosis of psoriasis,and puts forward a new method of combining Lingnan fire needling and filiform needling acupuncture technique to treat psoriasis vulgaris with blood stasis syndrome.Professor ZHOU Peng believes that the treatment principle of this disease is"regulating the mind first,rectifying blood as a base,syndrome differentiating and eliminating pathogenic factors",aiming at comprehensively considering the etiology and symptoms,in order to achieve more effective treatment results.Combined with the analysis of dermoscopic signs,it provides a possible improvement direction for the treatment of psoriasis vulgaris from a new perspective.

AIM:To investigate the effects of Panax notoginseng compound formula(PN)on endometrial fibro-sis by regulating inflammatory reaction and intestinal flora(IF)in a rat model of intrauterine adhesion(IUA).METHODS:The rat IUA model was established by following the mechanical injury method.A total of 50 rats were randomly divided in-to sham group,model group,low-dose(210 mg/kg)PN group,medium-dose(420 mg/kg)PN group and high-dose(840 mg/kg)PN group.After 8 weeks of intragastric administration,the uterus was collected to observe morphological changes with naked eye.The degree of uterine tissue damage and fibrosis was evaluated through hematoxylin-eosin(HE)and Mas-son staining.The collagen type Ⅰ(Col Ⅰ)was detected by immunohistochemistry.The interleukin-6(IL-6)and IL-10 pro-tein expression was detected by Western blot.The levels of IL-6,IL-1β,tumor necrosis factor-α(TNF-α)and vascular endothelial growth factor B(VEGFB)were detected by enzyme-linked immunosorbent assay(ELISA).The IF diversity and population structure were observed by 16S amplicon.RESULTS:Compared with the sham group,the uteruses of rats in the model group showed:reduced elasticity,accompanied by congestion and edema;decreased number of glands and blood vessels,and thinned endometrium(P<0.01);increased collagen fibers and Col Ⅰ protein expression(P<0.01);sig-nificantly increased IL-1β,IL-6,TNF-α and VEGFB levels in the uterine tissue(P<0.01);decreased IL-10 level(P<0.01);and reduced IF diversity(P<0.05).Compared with the model group,the drug intervention groups exhibited:re-covered elasticity of the uterus and relieved congestion and edema;increased number of endometrial glands and blood ves-sels(P<0.05);decreased collagen fibers and Col Ⅰ protein expression(P<0.01);reduced IL-1β,IL-6,and TNF-α lev-els to varying degrees in the uterine tissue(P<0.05);elevated IL-10 level(P<0.01);and improved IF diversity(P<0.05).CONCLUSION:The PN is able to significantly improve the endometrial tissue fibrosis in IUA rats.The under-lying mechanisms may be related to the inhibition of IL-6,IL-1β and TNF-α expression,up-regulation of IL-10,and im-provement of IF diversity.