ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. ConclusionIn patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.

OBJECTIVE To investigate the causal relationships between gut microbiota， blood metabolites and antidepressant treatment response from a genetic perspective， and to assess the potential mediating role of blood metabolites. METHODS This study utilized a two-sample Mendelian randomization （MR） design. Exposure data were derived from four large-scale gut microbiome genome-wide association study （GWAS） datasets and two blood metabolite GWAS datasets. The inverse variance weighted method was used as the primary method to evaluate the causal relationships between gut microbiota， blood metabolites and antidepressant effects. The robustness， heterogeneity and horizontal pleiotropy of the results were evaluated through various sensitivity analyses. Additionally， the false discovery rate （FDR） was applied to correct type Ⅰ errors caused by multiple hypothesis testing. Finally， MR mediation analysis was conducted to test the potential mediating effect of blood metabolites. RESULTS The s_ Bilophila was negatively associated with the effectiveness of antidepressant treatment （ P ＝8.030×10 －5 ， then P ＝0.033 after FDR correction）， and the f_Bacteroidales was positively associated with the effectiveness of antidepressant treatment （ P ＝3.275×10 －4 ， then P ＝0.034 after FDR correction）. Over a hundred blood metabolites were also screened out as being associated with antidepressant response， but after FDR correction， no significant causal relationship was observed. The P value of the mediation effect proportion of blood metabolites in the “gut microbiota-blood metabolites-antidepressant efficacy” pathway was greater than 0.05. CONCLUSIONS The s_ Bilophila may represent a risk factor for antidepressant effects， whereas the f_Bacteroidales may serve as a protective factor for antidepressant effects. The correlation between blood metabolites and antidepressant efficacy is not strong， and no genetic evidence is found to support that the investigated blood metabolites play a key mediating role between the gut microbiota and antidepressant response.

ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.

Objective To systematically review the studies on predictive models for delayed graft function (DGF) after kidney transplantation. Methods Databases including China Biology Medicine Database, China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Web of Science and CINAHL were searched to collect studies on predictive models for DGF after kidney transplantation published from the establishment of each database to June 29, 2025. Two researchers screened the literatures according to the inclusion and exclusion criteria, evaluated the quality of the literatures using the prediction model risk of bias assessment tool (PROBAST), and conducted a meta-analysis of the common predictors of the models using R software. Results A total of 12 literatures were included, involving 14 predictive models with sample sizes ranging from 103 to 24 653 cases. Donor serum creatinine level, cold ischemia time, donor age and donor body mass index were the top four common predictors. All the predictive models were at high risk of bias and low in applicability. The results of meta-analysis showed that abnormal donor body mass index, advanced donor age, prolonged cold ischemia time and elevated donor serum creatinine level were all associated with an increased risk of DGF after transplantation (all P<0.01), but there was high heterogeneity among the studies. Fixed-effect model and random-effect model were used to re-pool the effect sizes separately. The results indicated that the fixed-effect model and random-effect model had good consistency in terms of donor body mass index, donor age and cold ischemia time, while there was a significant difference in the effect sizes of the two models for donor serum creatinine level. Conclusions The predictive models for DGF risk after kidney transplantation have good predictive performance, but the overall risk of bias is high. In the future, large-sample, multicenter and high-quality prospective clinical studies should be carried out to optimize the predictive models, so as to improve their predictive ability and clinical application value.

ObjectiveTo investigate the association of hepatic steatosis with the level of viral replication and the progression of hepatic fibrosis in patients with chronic hepatitis B （CHB） through a real-world study， and to determine the independent influencing factors for hepatic fibrosis. MethodsA total of 887 CHB patients who attended the outpatient service and inpatient ward of Hepatology in The First Affiliated Hospital of Dalian Medical University from July 2021 to March 2025 were enrolled as subjects， and according to the presence or absence of metabolic dysfunction-associated steatotic liver disease （MASLD）， they were divided into CHB group with 560 patients and CHB+MASLD group with 327 patients. The association between hepatic steatosis and HBV load in CHB patients was analyzed， as well as the impact of varying degrees of hepatic steatosis on hepatic fibrosis. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a Spearman correlation analysis was performed； a Logistic regression analysis was used to investigate influencing factors. ResultsThe patients enrolled received antiviral therapy according to viral load； of all patients， 275 （31%） received nucleos（t）ide analogue combined with pegylated interferon-α， 532 （60%） received nucleos（t）ide analogue monotherapy， and 80 （9%） did not receive antiviral therapy. A total of 44 patients （5.0%） who were receiving PEG-IFN-α therapy and had marked thrombocytopenia were excluded， and finally 843 patients were included for comparison of aspartate aminotransferase-to-platelet ratio index （APRI） and fibrosis-4 index （FIB-4）. Compared with the CHB group， the CHB+MASLD group had a significantly higher proportion of male patients （χ²=5.917， P<0.05） and a significant increase in CAP value （t=21.646， P<0.05）. The median values of liver function parameters for the population enrolled were within the normal range， and no significant inflammatory activity was observed. The virological analysis showed that compared with the CHB group， the CHB+MASLD group had significantly lower serum level of pregenomic RNA （Z=-2.894， P<0.05） and HBeAg positivity rate （χ²=8.725， P<0.05）， and CAP was significantly negatively correlated with pgRNA （r=-0.117， P<0.05）. In the HBeAg-negative subgroup， compared with the CHB group， the CHB+MASLD group had a significantly lower level of hepatitis B surface antigen （Z=-0.765， P<0.05）； in the HBeAg-positive subgroup， the CHB+MASLD group had a significantly higher level of HBV DNA than the CHB group （Z=-2.509， P<0.05）. The analysis of hepatic fibrosis showed that the CHB+MASLD group had significantly lower values of APRI （Z=-3.418， P<0.05） and FIB-4 （Z=-6.237， P<0.05）. Compared with the CHB group， the CHB+MASLD S1 group had a significantly higher proportion of patients without fibrosis and a significantly lower proportion patients with liver cirrhosis （χ²=7.935， P<0.05）； in the CHB+MASLD S2 group， there was no significant difference in the proportion of patients with different fibrosis stages； the CHB+MASLD S3 group had a significantly lower proportion of patients without fibrosis and a significantly higher proportion of patients with early-stage fibrosis （χ²=9.101， P<0.05）. The Logistic regression analysis showed that an increase in CAP （odds ratio ［OR］=1.08， 95% confidence interval ［CI］： 1.03 — 1.13， P<0.05）， an increase in age （OR=1.02， 95%CI： 1.01 — 1.04， P<0.05）， male sex （OR=1.77， 95%CI： 1.19 — 2.64， P<0.05）， an increase in HBV DNA （OR=1.35， 95%CI： 1.15 — 1.57， P<0.001）， an increase in aspartate aminotransferase （OR=1.02， 95%CI： 1.01 — 1.03， P<0.001）， and an increase in gamma-glutamyl transpeptidase （OR=1.00， 95%CI： 1.00 — 1.01， P=0.028） were independent influencing factors for hepatic fibrosis. The risk of hepatic fibrosis in S3 patients was higher than that in patients without steatosis （OR=5.05， 95%CI： 2.48 — 10.29， P<0.001）. ConclusionThere is a lower level of HBV replication in CHB patients comorbid with MASLD. Hepatic steatosis is associated with HBV-related virological markers and the progression of hepatic fibrosis， and severe fatty liver disease may promote the progression of hepatic fibrosis in CHB patients.

OBJECTIVE To investigate the clinical characteristics of euglycemic diabetic ketoacidosis （euDKA） induced by empagliflozin， and provide references for safe medication. METHODS Case reports of euDKA induced by empagliflozin were retrieved and analyzed from PubMed， Web of Science， CNKI， and Wanfang Data. The Naranjo’s scale was adopted to assess the causal relationship between empagliflozin and euDKA. RESULTS A total of 29 patients were enrolled， including 16 males and 13 females，with a median age of 58 years. All patients were diagnosed with type 2 diabetes mellitus； 22 patients had at least one comorbidity. The median time to euDKA onset was 60 days after administration， and 7 cases occurred within 2 weeks of treatment. Perioperative periods，fasting，and low-carbohydrate or ketogenic diets were the main predisposing factors. Common presentations included nausea，vomiting， fatigue， tachypnea，and tachycardia. The causal relationship between empagliflozin and euDKA was assessed as “probable” in all cases. According to adverse reaction severity grading， 13 cases were grade 3 （severe） and 16 cases were grade 4 （life-threatening）. All patients discontinued empagliflozin and recovered after corresponding treatment. CONCLUSIONS euDKA is a serious adverse reaction to empagliflozin， which mostly occurs early in treatment. Perioperative periods， fasting， and ketogenic diets are prone to induce euDKA. Elderly patients and those with comorbidities are at higher risk. Risk assessment should be conducted before clinical administration； blood ketones and acid-base monitoring should be strengthened in the early medication period； withhold the drug before elective surgery， avoid prolonged fasting；upon diagnosis， discontinue empagliflozin and initiate intravenous insulin， provide fluid resuscitation promptly， and use other treatments to improve patient prognosis.

Objective:To determine the optimal cut-off value of serum cotinine for distinguishing smoking status among Chinese adults based on a large-scale national sample.Methods:A cross-sectional study was conducted among 8 987 Chinese adults aged 20-79 years from 152 administrative counties across 31 provinces during 2017-2018. Sociodemographic characteristics, lifestyle, smoking status, and health status were collected via questionnaires and physical examinations. Blood samples were analyzed for serum cotinine levels using liquid chromatography-mass spectrometry and for blood creatinine levels using the picric acid method. Receiver operating characteristic (ROC) curve analysis was performed with serum cotinine concentration as the test variable and self-reported smoking status as the state variable. The optimal cut-off value was determined based on the maximum Youden′s index, and the bootstrap method was used for repeated sampling (2 000 times) to evaluate the confidence interval of the cut-off value. The net reclassification index (NRI) was used to evaluate the discrimination ability of the cut-off value of this study, the cut-off value of the American population 1 (total population: 3.3 μg/L, men: 4.1 μg/L, women: 3.0 μg/L) and the cut-off value of the American population 2 (the recommended value of the United States Centers for Disease Control and Prevention for the total population: 10.0 μg/L) against the smoking status of the Chinese population. Statistical analyses were conducted using IBM SPSS 27 and Python 3.11, with a significance level of α=0.05.Results:The age of the research subjects was (49.2±15.2) years. Among them, males accounted for 49.8% (4 477); smokers accounted for 28.8% (2 586); the detection rate of serum cotinine was 94.6% (8 501), and the M ( Q1, Q3) concentration of serum cotinine was 0.9 (0.3, 85.4) μg/L. The ROC curve analysis results showed that the cut-off value (95% CI) of serum cotinine in the total population was 8.8 (6.7-11.7) μg/L, with the specificity (95% CI) about 93.6%(92.7%-94.3%), the sensitivity (95% CI) about 91.0%(89.7%-92.3%) and the area under the curve (AUC) (95% CI) about 0.93 (0.92-0.94). The cut-off value (95% CI) of cotinine for males was 17.1 (8.8-21.8) μg/L, with the specificity (95% CI) about 90.7%(87.9%-92.0%), the sensitivity (95% CI) about 89.4%(88.4%-92.2%) and the AUC (95% CI) about 0.92 (0.91-0.93). The cut-off value (95% CI) of cotinine for females was 7.4 (3.3-15.0) μg/L, with the specificity (95% CI) about 95.6%(92.7%-96.8%), the sensitivity (95% CI) about 87.6%(81.6%-92.8%) and the AUC (95% CI) about 0.92 (0.87-0.95). The NRI analysis results showed that compared with the cut-off value of the American population 2, the NRI of this study′s cut-off values in the total population, males and females were 0.020 ( P=0.015), 0.033 ( P=0.015) and 0.011 ( P=0.380), respectively, indicating that this study′s cutoff value could have better classification performance in the total population and males. Compared with the cut-off value of the American population 2, the NRI of the total population in this study was 0.001 ( P=0.285). Conclusion:The serum cotinine cut-off value based on the analysis of large sample data in China is more suitable for distinguishing the smoking status of Chinese adults.

Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.

OBJECTIVE To explore the colonization rates of carbapenem-resistant gram-negative bacteria(CRGNB)in intestinal tracts of intensive care unit(ICU)patients and analyze the influencing factors.METHODS The ICU patients were recruited from a three-A general hospital of Shanghai from Jan.2024 to Dec.2024,an ac-tive screening was carried out for intestinal tract CRGNB,and the detection rates of 5 types of carbapenems resist-ance genes(CRGs)in the CRGNB strains were observed.The baseline data and hospitalization data before the ac-tive screening were collected from the patients,logistic regression analysis was performed for the influencing fac-tors for the colonization of CRGNB.The effects of targeted infection control measures on length of ICU stay,hos-pitalization cost and prognosis were observed and compared before and after the active screening was carried out.RESULTS A total of 748 patients were included in the active screening,and the colonization rate of CRGNB in intestinal tracts was 11.50％(86/748).Among the CRGs,the detection rate of blaNDM was the highest(6.82％),followed by blaIMP(4.55％)and blaKPC(2.54％).The result of logistic regression analysis showed that,with an increase of 1 each day of hospital stay before the admission to ICUs,the risk was increased by 1.055 times(OR=1.055,95％CI:1.030 to 1.081,P＜0.001),the risk was 0.442 times the use of as aminoglycosides as the use of β-lactams(OR=0.442,95％CI:0.244 to 0.801,P=0.007).The targeted infection control measures that were taken after the active screening shortened the length of hospital stay(Z=-3.514,P＜0.001),reduce the hospitalization cost(Z=3.030,P=0.002)and improve the prognosis of the patients(x2=7.470,P=0.006).CONCLUSIONS The colonization rates of CRGNB in intestinal tracts are high among the ICU patients.It is necessary to reduce the length of hospital stay prior to ICU and strengthen the surveillance of drug-resistant strains and management of antibiotics.

Objective To establish a highly sensitive and specific method for detecting human DNA based on real time quantitative PCR(qPCR)technique for the rapid detection of potential DNA con-tamination sources in DNA laboratories.Methods Primers and probes were designed with Primer Ex-pressTM software using the reference sequence of human 18S rRNA gene as a template,and the opti-mal prime-probe combination was screened by matrix method.The PCR products of the target se-quence of human 18S rRNA gene were used to construct the plasmid,and a plasmid standard was used to draw the standard curve of the qPCR system.According to the Minimum Information for Pub-lication of Quantitative Real-time PCR Experiments(MIQE)guidelines,the specificity,sensitivity,re-peatability and application effect of the qPCR system were evaluated.Results The sensitivity of the qPCR system established in this study was 5.3×10-5 ng/μL,which showed good specificity for human DNA samples.The correlation coefficient of the qPCR system was-0.999,and amplification efficiency was 100％.Both the intra-batch and inter-batch variation coefficients were less than 2％.Conclusion The established human DNA detection method based on qPCR technique has good specificity,high sen-sitivity,and robust stability.It can be used for rapid detection of DNA contamination and daily moni-toring of the accumulated human DNA in the laboratory environment.