Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P＜0.001;r=0.466,P＜0.001);ADL was positively correlated with sleep quality(r=0.294,P＜0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P＜0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.

Objective:To investigate the current situation of satisfaction with graduate education among recent medical graduates in China, and analyze the differences between different populations, and to propose countermeasures and suggestions.Methods:From June to July 2023, a self-made questionnaire was used to survey 16 903 medical graduates who had recently earned a post-graduate degree from 78 institutions about their satisfaction with curriculum sessions, practical sessions, research training, tutoring, and institutional management. The degrees of satisfaction with education among different populations were compared through the t test and analysis of variance with the use of SPSS 26.0. Results:The scores of satisfaction of the graduates with tutoring, curriculum sessions, practical sessions, institutional management, and research training were 4.44, 4.03, 4.02, 3.90, and 3.82, respectively. Satisfaction scores for individual dimensions were significantly higher for males, doctors, non-transfers, comprehensive universities, non-agricultural household registration, moderate-to-high annual household income per capita, parents with high educational levels, and parents with mid- or senior-level occupations ( P<0.05). Conclusions:There is room for improvement in students' satisfaction with medical graduate education. To improve the quality of medical graduate education, attention should be paid to key populations, education policies, school management, and tutoring to provide appropriate education for different students.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

Objective:To investigate the current status of and relationship between practice efficacy, professional identity, and anxiety among public health master's graduates.Methods:From a national survey on the satisfaction with education of fresh medical master's graduates conducted from June to July, 2022, we selected 461 master's graduates of public health with internship experience from 49 institutions. With the use of SPSS 21.0, we compared the scores of practice efficacy, professional identity, and self-rated anxiety by personal characteristics through t-tests and analysis of variance; and explored the mediating role of anxiety in the relationship between practice efficacy and professional identity through stratified regression analysis. Results:The public health master's graduates scored (3.47±1.23) points for anxiety, (3.92±0.88) points for practice efficacy, and (4.33±0.77) points for professional identity. The score of anxiety differed significantly by sex, the degree of being affected by public health emergencies/major outbreaks, and internship initiative (all P<0.05). The score of practice efficacy was significantly different by sex, the type of institution, the degree of being affected by public health emergencies/major outbreaks, and internship initiative (all P<0.05). The score of professional identity differed significantly by sex, the type of institution, major transfer, the degree of being affected by public health emergencies/major outbreaks, internship initiative, and internship duration (all P<0.05). Professional identity was positively correlated with practice efficacy ( r=0.652, P<0.01) and negatively correlated with anxiety ( r=-0.213, P<0.05). The stratified regression results showed that practice efficacy positively influenced professional identity ( β=0.782, P<0.001), and anxiety partially mediated the relationship between the two ( β=-0.104, P<0.05). Conclusions:Anxiety plays a mediating role in the relationship between practice efficacy and professional identity, suggesting that reducing anxiety can help enhance practice efficacy to promote the professional identity of public health master's graduates.

Objective To explore the effectiveness of different intervention strategies in response to outbreaks of emerging highly pathogenic respiratory infectious diseases(RIDs)in mega-city in China,and provide decision-ma-king basis for effective response to emerging RIDs.Methods A susceptible-exposed-infectious-recovered(SEIR)transmission dynamics model was constructed,referencing to and combining the pathogenicity and infectivity para-meters of previous emerging RIDs.The outbreak of emerging highly pathogenic RIDs with low,moderate,and high infectivity in a mega-city with a population of 10 million in China was simulated,the development of the epidemic within 100 days after implementing different combinations of non-pharmaceutical interventions(NPIs)in response to the outbreak was compared.Results When highly pathogenic RIDs outbreak occurred,and if its infectivity was low(R0 was about 1.5),it was unnecessary to adopt strict NPIs to control epidemic.If its infectivity was moderate(R0 was about 6),different intensities of NPIs were needed based on its existing infection scale.When the initial num-ber of infected cases was 50,moderate-intensity NPIs could keep the infection and death at a low level within 100 days,and the required bed number in hospital for cases could be kept below the national average reserve level.But when the scale of infection exceeded 100 cases,high-intensity NPIs were needed to control the development of the epidemic.In the case of extremely strong infectivity(R0 was about 10),regardless of the scale of infection,only immediate high-intensity NPIs could control the epidemic,infection and death scale.Conclusion In case of out-breaks of highly pathogenic RIDs,adopting appropriate NPIs as early as possible based on their epidemiological characteristics and infection scale is necessary to minimize the harm to the population.

Objective To explore the clinical characteristics and treatment strategies of infective endocarditis caused by Bartonella vinsonii subsp.berkhoffii(Bvb).Methods Clinical diagnosis and treatment of a 25-year-old male patient with infective endocarditis caused by Bvb in China was reported,combined with literatures about three similar cases reported abroad were summarized and analyzed.Results All 4 patients were young and middle-aged males with a history of close contact with canines in the past one year.The main symptoms were chest pain,fa-tigue,and dyspnea,accompanied by cerebrovascular accidents and severe anemia,as well as the formation of heart valve vegetations and valve function impairment.Multiple blood cultures were negative,2 and 3 cases were con-firmed to be infected with Bvb through metagenomic next-generation sequencing(mNGS)of pathogenic microorga-nisms and polymerase chain reaction respectively.All patients underwent surgical treatment due to heart failure,and all survived after surgery and targeted anti-infective treatment.Conclusion This case report is the first case of Bvb infective endocarditis in China.Patient's diagnosis is confirmed by serum indirect immunofluorescence assay and mNGS,combination of surgery and anti-infective treatment has achieved ideal effect.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

The cartilage-protective effect of ginkgolide C(GC)on the two modeling modalities was investigated based on joint pain,degree of cartilage pathology,ECM degradation process,and level of inflammatory mediator production in rats.Twenty-five SD rats were selected and randomly di-vided into five groups:the control group(Control group),model 1 group(ACLT group),adminis-tration 1 group(ACLT+GC group),model 2 group(MIA group),and administration 2 group(MIA+GC group.)The rats were euthanized after 4 weeks of the test.Femur,tibia and blood samples were collected from the right hind limb of rats.The degree of pathology in the femur and tibia of rats was assessed by saffron O solid green staining and OARSI score.Immunohistochemis-try was used to detect the expression levels of collagen Ⅱ and MMP-13 in cartilage.ELISA was used to detect the changes in the levels of MMP-3,MMP-13,CTX-Ⅱ,COMP,COX-2,INOS,IL-1β,and TNF-α in the serum of rats.Cold sensitivity test and knee extension vocalization test were conducted to detect the degree of joint pain in rats.ACLT could cause more severe structural dam-age to articular cartilage compared with the MIA group.The OARSI scores and the expression of MMP-13 in femur and tibia,and the serum levels of MMP-13,MMP-3,CTX-Ⅱ,and COMP were higher in the ACLT group than those in the MIA group.However,the levels of inflammatory me-diators COX-2,IL-1β,and TNF-α were significantly lower in the ACLT group than in the MIA group(P＜0.0l).GC intervention reduced the OARSI score(P＜0.05 or P＜0.01)and pain scores,inhibited the ECM matrix degrading enzymes(MMP-13,MMP-3),cartilage metabolism markers(CTX-11,COMP),and inflammatory mediators(COX-2,INOS,IL-1β and TNF-α)ex-pression,and promoted collagen Ⅱ synthesis.Both modeling methods resulted in cartilage damage.In particular,the OA model constructed by ACLT+PMMx method in rats had obvious joint dam-age,which was favorable to investigate the degree of cartilage structural damage.GC attenuated cartilage pathological changes,pain severity and inflammatory response in the rat OA model in both groups,thus exerting a cartilage-protective effect.