ObjectiveTo investigate the effects and underlying mechanisms of polydatin in delaying the progression of colitis-associated colorectal cancer （CAC） by constructing an azoxymethane （AOM）/dextran sulfate sodium （DSS）-induced CAC mouse model and conducting in vitro experiments. MethodsFifty-four male C57BL/6J mice were randomly divided into normal， model， and polydatin groups （0.045 g·kg^-1）. The CAC mouse model was established using AOM/DSS， and samples were collected at 4， 7， and 10 weeks. Body weight change rate， disease activity index （DAI）， and tumor formation were assessed. Hematoxylin-eosin （HE） staining was used to observe pathological injury in intestinal tissues. Immunohistochemistry （IHC） was performed to detect zonula occludens-1 （ZO-1） expression in colonic tissues， and Western blot was used to detect the expression of E-cadherin， N-cadherin， and Vimentin in colonic epithelial cells. Real-time PCR was used to measure mRNA expression of interleukin-17A （IL-17A）， Wnt3a， β-catenin， T cell factor 1 （Tcf1）， E-cadherin， N-cadherin， and Vimentin in colonic tissues. Flow cytometry was used to analyze the proportion of CD8⁺T cells and the expression of exhaustion-related molecules in tumors. Human colon cancer DLD-1 cells were cultured in a polydatin-containing medium， and wound healing assays were performed to observe migration changes. Real-time PCR was used to detect mRNA expression of interleukin-17 receptor A （IL-17RA）， Wnt3a， β-catenin， Tcf1， E-cadherin， N-cadherin， and Vimentin in DLD-1 cells. ResultsCompared with the normal group， the model group at all three time points showed significantly decreased body weight change rate （P<0.01）， significantly shortened colon length （P<0.01）， and markedly increased DAI scores （P<0.01）. HE staining revealed significant inflammatory cell infiltration in the submucosa of the colon in the model group， accompanied by epithelial dysplasia. ZO-1 expression in colonic tissues was significantly reduced （P<0.01）. The mRNA expression of the pro-inflammatory factor IL-17A and key molecules of the Wnt/β-catenin pathway （Wnt3a， β-catenin， Tcf1） was significantly elevated （P<0.05）. The mRNA and protein expression of epithelial-mesenchymal transition （EMT） markers N-cadherin and Vimentin was significantly upregulated （P<0.05）， while E-cadherin expression was significantly downregulated （P<0.05）. The proportion of tumor-infiltrating CD8⁺T cells expressing immunosuppressive molecules （TIM-3， LAG-3， PD-1） was significantly increased （P<0.05）. Compared with the model group， the polydatin group showed significant improvement in body weight and DAI score （P<0.01）， as well as recovery of colon length and tissue injury. ZO-1 expression in colonic tissue was significantly increased （P<0.01）， while IL-17A， Wnt3a， β-catenin， Tcf1， N-cadherin， and Vimentin expression levels were significantly decreased （P<0.05）， and E-cadherin expression was significantly increased （P<0.01）. Tumor-infiltrating CD8⁺ T cells expressing immunosuppressive molecules were significantly reduced （P<0.05）. In vitro experiments showed that polydatin significantly inhibited migration of DLD-1 cells （P<0.01） and reversed the upregulation of IL-17RA， Wnt3a， β-catenin， N-cadherin， and Vimentin mRNA， as well as the downregulation of E-cadherin mRNA （P<0.05）. ConclusionPolydatin inhibits IL-17A secretion and IL-17RA expression， improves the immune microenvironment， blocks activation of the Wnt/β-catenin signaling pathway， suppresses EMT markers （N-cadherin and Vimentin）， and restores tight junction protein expression in intestinal epithelial cells， thereby delaying the progression from colitis to colorectal cancer in mice.

Objectives To explore the causal relationship between asthma-related pneumonia and heart failure(HF)by using two-sample Mendelian randomization(MR)analysis.Methods The causal relationship between asthma-related pneumonia and HF were systematically evaluated through two-sample MR analysis based on publicly available Genome-Wide Association Study data.Inverse variance weighted(IVW),MR-Egger,weighted median,weighted mode,and simple mode methods were used.Different models were used to analyze sensitivity.Testing approaches were conducted to assess the robustness of the results.Results IVW analysis results showed that there was a causal relationship between asthma-related pneumonia and HF risk(OR=1.113,95％CI:1.027-1.206,P=0.009).HF was not found to have a causal effect on asthma-related pneumonia risk based on IVW analysis(OR=1.018,95％CI:0.780-1.328,P=0.893).The variance used in all MR analyses showed no heterogeneity or horizontal pleiotropy.The leave-one-out analysis revealed that no single nucleotide polymorphism disproportionately influenced the results,further confirming the credibility of the bidirectional MR findings.Conclusion This study established a causal relationship between asthma-related pneumonia and HF risk.No clear causal relationship between HF and asthma-related pneumonia risk was found.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Diabetic retinopathy(DR)is one of the common serious microvascular complications in diabetic patients,with the main pathological features of retinal vascular injury,oxidative stress and chronic inflammatory re-sponse.In recent years,more and more studies have shown that mitophagy plays an important role in maintaining the func-tional homeostasis of retinal cells and preventing oxidative damage,and nucleotide-binding oligomerization domain-like re-ceptor protein 3(NLRP3)is a key regulator of pro-inflammatory response in DR.Mitophagy can reduce the excessive pro-duction of reactive oxygen species(ROS)by removing damaged mitochondria,thereby inhibiting the activation of NLRP3 inflammasome.In contrast,mitochondrial dysfunction can lead to excessive activation of NLRP3 inflammasome,which further aggravates the inflammatory response and apoptosis of the retina.Therefore,this article reviews the independent role of mitophagy and NLRP3 inflammasome in DR and their mutual regulatory mechanisms,so as to provide reference for the study of mitophagy and NLRP3 inflammasome as targets.

Objective:By analyzing the correlation between genotypes and phenotypes,we explored the impact of the variant c.917T＞C(p.L306P)in the ABO*B.01 allele on the expression and function of B-glycosyltransferase(GTB).This study aims to elucidate the molecular mechanisms underlying the occurrence of this subtype.Methods:The study subjects included a blood donor specimen with incompatible forward and reverse ABO typing results.ABO phenotyping was determined using ABO blood group serology and GTB activity testing.Subsequently,Sanger sequencing and third-generation sequencing based on the PacBio platform were employed to sequence the ABO gene,resulting in the determination of haplotype sequences.Mutations were identified through sequence alignment.An in vitro cell expression system was established to assess the impact of the mutation site on antigen expression.Results:The index case in this study was identified as B subtype with the allelic genotype c.917T＞C in ABO*B.01/ABO*O.01.01,which has not been previously reported.In vitro expression results revealed decreased levels of GTB expression and overall GTB activity in the mutant cells.Furthermore,the expression of the B antigen on the cell membrane was weaker in the mutant cells compared to the wild-type cells.Conclusion:The p.L306P variation caused by the c.917T＞C mutation in the ABO*B.01 allele may be a genetic factor contributing to the reduced expression of B antigens on the surface of red blood cells.

Objective:To understand the relationship between sleep duration and cardiovascular and metabolic comorbidities (CMM) in middle-aged and elderly people in China.Methods:This study was a prospective cohort study, based on the data of China Health and Retirement Tracing Survey (CHARLS) from 2011 to 2015, and included middle-aged and elderly people aged≥45 years in the cohort study. Age, gender, marital status, residence, education, smoking status, alcohol status, body mass index, history of diabetes, history of dyslipidemia, history of hypertension, history of stroke, history of heart disease, history of mental illness, depression scale score were collected. Multivariate logistic regression was used to analyze the association between daily sleep duration and the risk of CMM onset and to construct four models with stepwise adjusted covariates. A stratified analysis was established based on demographic factors, lifestyle factors, metabolic factors, cardiovascular and cerebrovascular factors, and psychological factors. Meanwhile, a subgroup analysis was established according to different combinations of cardiovascular and metabolic diseases to explore the association between sleep length and the risk of CMM in different populations.Results:A total of 297 (4.4%) of the 6 788 included participants experienced CMM. In the multivariate logistic regression, the RR value (95% CI) for the risk of CMM for>9 h was 1.99 (1.86-2.08) and 1.78 (1.64-1.92), respectively (all P<0.001). The stratified analysis showed that the risk of CMM incidence between sleep duration<7 h and>9 h was associated in people with different age, sex, residence, smoking status, drinking status, body mass index, hypertension, hypertension, diabetes, heart disease, stroke, dyslipidemia, and depression (all P<0.05). Subgroup analysis showed that sleep duration<7 h with both diabetes, heart disease and stroke had the highest risk of CMM ( RR=1.95, 95% CI: 1.65-2.14). Conclusion:In the middle-aged and elderly group in China, there is a U-shaped association between sleep duration and CMM, that is, insufficient or too long sleep duration throughout the day is related to the increased risk of CMM.

Objective:To investigate the association between triglyceride glucose index (TyG) and early vascular aging measured by brachial ankle pulse wave velocity (baPWV) in young and middle-aged population.Methods:It was a cross-sectional study. A total of 5 680 subjects aged 20 to 59 years who underwent health check-ups at the Health Management Center of General Hospital of Tianjin Medical University from January to December in 2020 were selected as the research subjects. All the research subjects completed the health risk assessment questionnaire, physical examination, laboratory test, and multi-functional vascular lesion detection. The TyG was calculated and the research subjects were divided into four groups with the quartiles of TyG (Q 1 to Q 4, with a cut-off value of 8.22, 8.60 and 9.01, respectively). The baPWV value was converted into a Z-score, and those with a Z-score above the 95th percentile were defined as having early vascular aging. The Spearman correlation method, multiple linear regression model, binary logistic regression model and the area under the receiver operating characteristic curve (AUC) were used to analyze the association between TyG and early vascular aging. Results:Among the 5 680 middle-aged and young people included in the analysis, there were 3 117 males and 2 563 females, with an age of 46 (39, 52) years, a TyG of 8.60 (8.22, 9.01), and a baPWV of 1 279.25 (1 147.50, 1 434.25) cm/s. The prevalence rate of early vascular aging was 5.02% (285/5 680). Taking group Q 1 as the reference, in the multiple linear regression model adjusted for multiple factors, group Q 4 was significantly associated with a 47.64 (95% CI: 28.18-67.11) cm/s increase in baPWV ( P for trend<0.001). In the multivariate adjusted binary logistic regression model, compared with that in the Q 1 group, the OR of early vascular aging occurrence in the Q 2, Q 3, and Q 4 groups was 1.52 (95% CI: 0.75-3.07), 1.78 (95% CI: 0.89-3.58), and 3.04 (95% CI: 1.47-6.31), respectively. Elevated TyG level was positively correlated with the occurrence of early vascular aging ( P for trend<0.001). The AUC of TyG in predicting early vascular aging was 0.732 (95% CI: 0.704-0.759), with the optimal cut-off value being 8.86. The AUC of TyG in predicting early vascular aging in males was lower than that in females [0.665 (95% CI: 0.628-0.702) vs 0.796 (95% CI: 0.748-0.843)] ( P<0.001). Conclusions:There is a correlation between TyG and early vascular aging measured by baPWV in the middle-aged and young population. When TyG≥8.86, clinical intervention measures should be taken in a timely manner.