Objective To investigate the protective effect of miR-193a-5p on cardiac function and the regulation of IL-33/ST2 signaling pathway in rats with chronic heart failure(CHF).Methods Forty SPF-grade Wistar rats were randomly divided to four groups:Sham group,CHF group,NC group,and miR-193a-5p group,10 rats in each group.The model of chronic heart failure was duplicated in the CHF group,NC group,and miR-193a-5p group.Subsequently,the rats in the NC group and miR-193a-5p group were received 5 nmol/L of NC-agomiR or miR-193a-5p-agomiR,respectively,via tail vein injection every 3 days for 4 weeks.In contrast,the rats in the Sham and CHF groups were received an equal amount of saline injection.At the endpoint of the experiment,doppler color ultrasonography was used to detect the left ventricular posterior wall thicknesses(LVPWs),left ventricular posterior wall thickness at end-diastole(LVPWd),systolic interventricular septal thicknesses IVSs,end-diastolic interventricular septal thicknesses(IVSd),and left ventricular ejection fractions(LVEFs)in the above rats,and the changes in the cardiac phenotypic indices of HW/BW vs.LVW/BW in the 4 groups,and cardiac tissues of the rats of the 4 groups were selected.Histomorphological analysis was performed,and the expression levels of miR-193a-5p in the cardiac tissues of the four groups of the rats were detected by qPCR;apoptosis was detected by Tunel staining;the levels of the inflammatory factors interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-alpha)in the myocardial tissues were measured by Elisa;Western blot was used to detect the expression levels of IL-33 and ST2 protein in myocardial tissues.Results Compared with the Sham group,the hearts in the CHF and NC groups showed increased volume,altered geometry,thinning of the myocardium,and pallor in the infarcted area,whereas the miR-193a-5p group showed partial remission.In addition,the expression levels of miR-193a-5p in cardiac tissues of the CHF and NC groups showed a decreasing trend,whereas showed a significant increase in the miR-193a-5p group(P<0.01).In CHF group and NC group,LVPWs,LVPWd,IVSS,IVSD HW/BW and LVW/BW increased significantly,and LVEF decreased significantly(P<0.01).In miR-193a-5p group,LVPWs,LVPWd,IVSs,IVSd,HW/BW and LVW/BW decreased significantly but higher than sham group,and LVEF increased significantly but lower than sham group(P<0.01).The expression of miR-193a-5p increased significantly in CHF group and NC group,decreased significantly in miR-193a-5p group but still higher than sham group(P<0.01).The expression of IL-33 and ST2 protein increased significantly in CHF group and NC group,and decreased significantly in miR-193a-5p group(P<0.01).Conclusion miR-193a-5p has a protective effect on cardiac function in the rats with chronic heart failure.The mechanism might be related to inhibiting the release of inflammatory factors,reducing cardiomyocyte apoptosis and the inhibition of IL-33/ST2 signaling pathway.

With the change of infectious disease incidence pattern and the development of related technologies, progresses have been made in the research of infectious disease epidemiology. In recent years, due to the change in the requirements of infectious disease prevention and control, the research focus has expanded from common infectious diseases to diseases which have been eliminated or might be eliminated, as well as emerging and re-emerging infectious diseases. Infectious disease data has been characterized by multiple sources and modalities. Along with the rapid development of pathogen detection methods, infectious disease surveillance has shifted from a single disease-targted one to a comprehensive one. Moreover, novel technologies such as multi-omics and artificial intelligence have been applied in infectious disease epidemiology research. The international cooperation in this field has become increasingly crucial, and the revision of the International Health Regulations and the negotiation of pandemic agreement will have a profound impact. In the future, infectious disease epidemiology research will develop with more powerful tools to improve its capabilities.

Objective:To explore the dynamic change trajectory and influencing factors of postoperative fatigue (POF) in patients with early digestive tract cancer undergoing endoscopic submucosal dissection (ESD), so as to provide theoretical basis for individualized management of such patients.Methods:Using cross-sectional survey and convenient sampling method, the patients who underwent ESD for early cancer of digestive tract in the endoscopic center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to June 2024 were selected as the research objects. The questionnaires were conducted at 30 min, 24 h, 3 days, 5 days, 7 days after ESD with Christensen's postoperative fatigue score. Spearman test was used to analyze the correlation between pain, insomnia and POF. The latent variable growth model was used to identify the potential categories of POF trajectory, and the influencing factors were analyzed by Logistic regression.Results:A total of 232 patients were finally induded, with ages of 19-94(59.53 ± 13.29) years, including 120 males and 112 femalss. The POF level of patients with early cancer of digestive tract showed a downward trend one week after operation. Three postoperative fatigue trajectories were fitted, 9.05% in moderate or severe fatigue low-speed smooth descent group (C1 group); 32.76% in moderate fatigue first decreased quickly and then slowly group (C2 group) and 58.19% in mild fatigue continuous decline group (C3 group). The result of Logistic regression analysis showed that, compared with C1 group, people without religious beliefs were morelikely to enter C2 group [ β = 1.572, OR = 4.818(1.033 - 22.465), P<0.05]; compared with C3 group, patients with high pain level and severe insomnia degree were likely to enter C1 [ β = 2.621, 0.663, OR were 13.754(2.692 - 70.283) and 1.942(1.429 - 2.638), both P<0.05] and C2 [ β = 2.010, 0.491, OR were 7.464(1.890 - 29.482) and 1.634(1.348 - 1.982), both P<0.05] group. Conclusions:There were three potential types of POF in patients with early digestive tract cancer ESD. Medical staff should pay attention to patients with severe insomnia, intense pain and religious beliefs, and give staged fatigue assessment and individualized intervention, so as to reduce the level of POF and promote rapid recovery.

With the change of infectious disease incidence pattern and the development of related technologies, progresses have been made in the research of infectious disease epidemiology. In recent years, due to the change in the requirements of infectious disease prevention and control, the research focus has expanded from common infectious diseases to diseases which have been eliminated or might be eliminated, as well as emerging and re-emerging infectious diseases. Infectious disease data has been characterized by multiple sources and modalities. Along with the rapid development of pathogen detection methods, infectious disease surveillance has shifted from a single disease-targted one to a comprehensive one. Moreover, novel technologies such as multi-omics and artificial intelligence have been applied in infectious disease epidemiology research. The international cooperation in this field has become increasingly crucial, and the revision of the International Health Regulations and the negotiation of pandemic agreement will have a profound impact. In the future, infectious disease epidemiology research will develop with more powerful tools to improve its capabilities.

Objective:To explore the dynamic change trajectory and influencing factors of postoperative fatigue (POF) in patients with early digestive tract cancer undergoing endoscopic submucosal dissection (ESD), so as to provide theoretical basis for individualized management of such patients.Methods:Using cross-sectional survey and convenient sampling method, the patients who underwent ESD for early cancer of digestive tract in the endoscopic center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to June 2024 were selected as the research objects. The questionnaires were conducted at 30 min, 24 h, 3 days, 5 days, 7 days after ESD with Christensen's postoperative fatigue score. Spearman test was used to analyze the correlation between pain, insomnia and POF. The latent variable growth model was used to identify the potential categories of POF trajectory, and the influencing factors were analyzed by Logistic regression.Results:A total of 232 patients were finally induded, with ages of 19-94(59.53 ± 13.29) years, including 120 males and 112 femalss. The POF level of patients with early cancer of digestive tract showed a downward trend one week after operation. Three postoperative fatigue trajectories were fitted, 9.05% in moderate or severe fatigue low-speed smooth descent group (C1 group); 32.76% in moderate fatigue first decreased quickly and then slowly group (C2 group) and 58.19% in mild fatigue continuous decline group (C3 group). The result of Logistic regression analysis showed that, compared with C1 group, people without religious beliefs were morelikely to enter C2 group [ β = 1.572, OR = 4.818(1.033 - 22.465), P<0.05]; compared with C3 group, patients with high pain level and severe insomnia degree were likely to enter C1 [ β = 2.621, 0.663, OR were 13.754(2.692 - 70.283) and 1.942(1.429 - 2.638), both P<0.05] and C2 [ β = 2.010, 0.491, OR were 7.464(1.890 - 29.482) and 1.634(1.348 - 1.982), both P<0.05] group. Conclusions:There were three potential types of POF in patients with early digestive tract cancer ESD. Medical staff should pay attention to patients with severe insomnia, intense pain and religious beliefs, and give staged fatigue assessment and individualized intervention, so as to reduce the level of POF and promote rapid recovery.

OBJECTIVE To evaluate the quality of diagnosis and treatment guidelines and expert consensuses on childhood immune thrombocytopenic purpura(ITP)published domestically and internationally,in order to provide reference for clinical practice and future guideline/expert consensus development and improvement.METHODS A systematic search was conducted across multiple databases,including PubMed,Cochrane Library,Embase,CNKI,Wanfang data,VIP,CBM;additionally,supplementary searches were carried out on websites such as Medlive,the Chinese Medical Association's official website,and National Institute for Health and Clinical Excellence in the UK.The retrieval time ranged from the inception to September 2,2024.Researchers who had undergone systematic training independently evaluated the methodology and report quality included in the guideline/consensus using the Appraisal of Guidelines Research and Evaluation Ⅱ(AGREE Ⅱ)and the Reporting Items for Practice Guidelines in Healthcare(RIGHT).RESULTS A total of 11 guidelines/consensuses were included.The average scores for the six domains of AGREE Ⅱ tool respectively were"range and purpose"[(66.67±17.98)%],"participants"[58.33%(13.89%,73.61%)],"rigor"[(41.81±23.85)%],"clarity"[(69.57±19.35)%],"applicability"[(35.98±17.83)%],and"independence"[27.08%(0,75.00%)];out of 11 articles,9 had a recommendation level of B,2 had a recommendation level of C,and there were no A-level articles.The average reporting rates of the 7 areas in the RIGHT tool were"basic information"[(72.35±12.95)%],"background"[(54.55±15.40)%],"evidence"[(36.36±24.81)%],"recommended opinions"[(53.25±19.20)%],"review and quality assurance"[0(0,25.00%)],"funding and conflict of interest statement and management"[12.50%(0,25.00%)],and other aspects[8.33%(0,50.00%)].In addition,there was no statistically significant difference in the AGREE Ⅱ and RIGHT scores between the guidelines and consensuses(P＞0.05).CONCLUSIONS The overall quality of the guidelines and consensuses included in this study is not high,with a recommended level of B or C.It is recommended that clinical decision-making prioritize referring to the relatively high-quality guideline/consensus among them.The quality of evidence in the existing traditional Chinese medicine guidelines for children with ITP needs to be improved,and there is no integrated guideline/consensus for traditional Chinese and Western medicine.It is recommended to revise or write relevant guideline/consensus according to the requirements of AGREE Ⅱ and RIGHT in various fields to guide clinical practice.

Objective To investigate the correlation between the total load of cerebral small vessel disease(CSVD)and the early prognosis of patients with acute cerebral infarction(ACI).Methods A total of 150 patients with ACI admitted to the Department of Neurology,the First Hospital of Jiaxing from October 2020 to June 2022 were included,according to modified Rankin scale(mRs)score,patients were classified good prognosis group(mRs≤2 points)and poor prognosis group(mRs≥3 points),baseline data and clinical characteristics were compared between the 2 groups,and total CSVD load was assessed by cranial MRI,single factor and multi-factor analysis were performed with Logistic model.The relativity of CSVD load and early prognosis was analyzed with Pearson method.Results Age,length of stay,National Institute of Health stroke scale(NIHSS),hypersensitivity C-reactive protein,triglyceride and homocysteine were significantly higher in poor prognosis group than those in good prognosis group,the difference was significant(P<0.05).The scores of lacunar,cerebral microhemorrhage,white matter hyperintensity and CSVD in poor prognosis group were significantly higher than those in good prognosis group(P<0.05).Multivariate Logistic regression analysis showed that length of stay(OR=1.278,95％CI=1.054-1.548,P=0.012),admission NIHSS score(OR=1.354,95％CI=1.113-1.647,P=0.002),CSVD total load(OR=2.494,95％CI=1.666-3.735,P<0.001)were independent risk factors for poor early prognosis in patients with acute cerebral infarction.Conclusion CSVD load is associated with poor prognosis in patients with acute cerebral infarction.

AIM:To study the effect of hepatitis B combined with hepatic fibrosis on endogenous and exogenous metabolism of liver and the effect of glycyrrhizic acid combined with tenofovir(TFV)es-ter on anti-HBV efficacy.METHODS:Hepatitis B mouse was induced by chronic CCI4 to form a mod-el of hepatitis B with hepatic fibrosis.H&E staining,Sirius Red Staining,α-SMA immunohistochemistry were used to detect pathological changes in liver tissue.The changes of liver endogenous metabo-lism in mice with hepatitis B and hepatic fibrosis were detected by metabolomics.LC-MS/MS was used to investigate the plasma and liver concentra-tions of TFV and its active metabolite(TFV-DP),for investigating the changes of exogenous metabo-lism.RESULTS:HBV+CCl4 mice showed fibrosis symptoms such as liver injury and collagen deposi-tion.Hepatitis B combined with hepatic fibrosis af-fected nucleotide metabolism,amino acid metabo-lism,tricarboxylic acid cycle,pentose phosphate pathway and other endogenous metabolism,low-ered the hepatic level of TFV-DP,and decreased the antiviral efficacy.By combining with glycyrrhizic acid or forming a self-assembled preparation,the hepatic level of TFV-DP was improved,and the anti-viral efficacy was enhanced.CONCLUSIONS:Hepati-tis B combined with hepatic fibrosis affected both endogenous and exogenous metabolism of liver.Different forms of combination of glycyrrhizic acid and TFV could elevate the level of TFV-DP in liver and improve the antiviral efficacy in HBV+CCI4 mice.

Neuropeptide Y receptor Y8(NPY8R)is a fish-specific receptor with two subtypes,NPY8AR and NPY8BR.Changes in expression levels during physiological processes or in vivo regulation after ventricular injection suggest that NPY8BR plays an important role in feeding regulation;this has been found in only a few fish,at present.In order to better understand the physiological function of npy8br,especially in digestion,we used clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)technology to generate npy8br-/-Japanese medaka(Oryzias latipes).We found that the deletion of npy8br in medaka larvae affected their feeding and digestion ability,ultimately affecting their growth.Specifically,npy8br deficiency in medaka larvae resulted in decreased feed intake and decreased expression levels of orexigenic genes(npy and agrp).npy8br-/-medaka larvae fed for 10 d(10th day of feeding)still had incompletely digested brine shrimp(Artemia nauplii)in the digestive tract 8 h after feeding,the messenger RNA(mRNA)expression levels of digestion-related genes(amy,lpl,ctra,and ctrb)were significantly decreased,and the activity of amylase,trypsin,and lipase also significantly decreased.The deletion of npy8br in medaka larvae inhibited the growth and significantly decreased the expression of growth-related genes(gh and igf1).Hematoxylin and eosin(H&E)sections of intestinal tissue showed that npy8br-/-medaka larvae had damaged intestine,thinned intestinal wall,and shortened intestinal villi.So far,this is the first npy8br gene knockout model established in fish and the first demonstration that npy8br plays an important role in digestion.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.