Objective:To investigate gut microbiota differences between individuals with and without colorectal adenoma(CRA)and to identify gut microbes associated with CRA.Methods:This cross-sectional study analyzed the gut microbiota of 100 patients with CRA and 68 individuals without CRA(aged 40-75 years)who underwent colonoscopies between March 2021 and March 2022 at Tianjin Nankai Hospital.Fecal samples were sequenced for the V3-V4 region of the bacterial 16S rRNA gene using the Illumina NovaSeq platform.Results:Compared to the non-CRA group,the CRA group exhibited reduced relative abundances of identified and unidentified Lachnospiraceae,with increased Faecalibacterium and Streptococcus.In the non-CRA group,the relative abundances of Coprococcus,unidentified Clostridiaceae,and Clostridium were higher.LEfSe analysis revealed significant enrichment of Gammaproteobacteria,Proteobacteria,Enterobacteriales,and Faecalibacterium in the CRA group,while the non-CRA group was enriched for Moraxellaceae,Acinetobacter,and Anaerostipes.Conclusions:These findings suggest a discernible disparity in the gut microbiota structure between CRA patients and individuals without adenoma.The enrichment of potential pathogenic taxa,such as Faecalibacterium and Streptococcus,in the CRA group suggests a possible association with adenoma development.

Objective:To investigate the effect of natural plant compound puerarin(PUE)on expression of NLRP3 inflamma-some in macrophages and its effect in ulcerative colitis(UC)in mice.Methods:A mouse model of UC was established using dextran sulfate sodium(DSS).Mice received PUE via gavage for 7 consecutive days,body weight,disease activity index and colon length were measured.HE staining was performed to assess tissue pathological damage.Flow cytometry was used to determine the proportion of peripheral blood mononuclear cells in colonic lamina propria.Immunofluorescence was employed to assess the colocalization of NLRP3 inflammasome and macrophages.qRT-PCR was conducted to measure mRNA expression levels of pro-inflammatory cytokines and NLRP3-related genes in colonic tissues.Protein expression levels of ZO-1,Occludin,cleaved caspase-1 and IL-1β in colonic tissues were detected by Western blot.A cell model was established using lipopolysaccharide(LPS)and adenosine triphosphate(ATP).mRNA expression levels of genes related to NLRP3 inflammasome were detected by qRT-PCR.Western blot was used to detect effects of PUE on expression levels of proteins related to NLRP3 inflammasome and NF-κB signaling pathway.Results:PUE treatment signifi-cantly improved symptoms of DSS-induced UC in mice,including body weight,disease index,colon length and pathological damage.Following PUE intervention,infiltration of Ly6C+MHC Ⅱ-monocyte derived macrophages in the colonic lamina propria was reduced.Expression levels of pro-inflammatory cytokines and NLRP3 inflammasome related molecules in colonic tissues were decreased.PUE treatment increased expression levels of ZO-1 and Occludin in intestinal epithelial cells.In vitro experiments confirmed that PUE reduced expression levels of NLRP3 inflammasome-related molecules in macrophages induced by LPS combined with ATP,as well as protein expression level of p-NF-κB p65.Conclusion:PUE significantly alleviates the symptoms of UC by reducing intestinal tissue inflamma-tion and repairing the epithelial barrier.The mechanism may involve regulating NF-κB signaling pathway,thereby reducing the forma-tion and activation of NLRP3 inflammasome in macrophages.

Objective To identify determinants of subtherapeutic voriconazole(VRCZ)concentrations in allogeneic hematopoietic stem cell transplantation(allo-HSCT)recipients and to develop/validate a nomogram-based risk prediction model.Methods This study retrospectively analyzed 310 VRCZ therapeutic drug monitoring(TDM)measurements from allo-HSCT recipients at 310 patients who under went allo-HSCT surgery at Hebei Yanda Ludaopei Hospital from October 2022 to October 2024 and received VRCZ for the prevention and treatment of invasive fungal infections before transplantion were selected as the study subjects.Cases were stratified into target-concentration group(0.5～5.0μg/ml)and subtherapeutic group(<0.5μg/ml).Through single factor and multiple factor Logistic regression analysis,indeipendent predictive factors forvecz plasma concentration non-compliance were screened,and a column chart prediction model(NPM)was constructed.The performance of the model was evaluateding area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow(H-L)goodness-of-fit test,and decision curve analysis(DCA).Results Among 310 VRCZ-TDM measurements,71.61%(222/310)achieved target concentrations.Multivariate analysis showed that CYP2C19 intermediate metabolite,daily dose of cyclosporine A(CSA),daily dose of VRCZ,creatinine(Cr)>97 μmol/L,albumin(Alb)and C-reactive protein(CRP)were independent influencing factors for VRCZ blood drug concentration non-compliance(Wald χ2=4.046～13.221,all P＜0.05).The nomogram demonstrated excellent discrimination,calibration(H-L goodness of fit test χ2=2.663,P=0.954),and clinical utility with net benefit across 0.05～0.96 risk thresholds.Conclusion The nomogram incorporating CYP2C19 gene phenotype,daily CSA dosing,daily VRCZ dosing,Cr levels,Alb and CRP provides a validated tool for optimizing VRCZ therapy in allo-HSCT recipients,enabling precision dosing strategies.

Objective To identify determinants of subtherapeutic voriconazole(VRCZ)concentrations in allogeneic hematopoietic stem cell transplantation(allo-HSCT)recipients and to develop/validate a nomogram-based risk prediction model.Methods This study retrospectively analyzed 310 VRCZ therapeutic drug monitoring(TDM)measurements from allo-HSCT recipients at 310 patients who under went allo-HSCT surgery at Hebei Yanda Ludaopei Hospital from October 2022 to October 2024 and received VRCZ for the prevention and treatment of invasive fungal infections before transplantion were selected as the study subjects.Cases were stratified into target-concentration group(0.5～5.0μg/ml)and subtherapeutic group(<0.5μg/ml).Through single factor and multiple factor Logistic regression analysis,indeipendent predictive factors forvecz plasma concentration non-compliance were screened,and a column chart prediction model(NPM)was constructed.The performance of the model was evaluateding area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow(H-L)goodness-of-fit test,and decision curve analysis(DCA).Results Among 310 VRCZ-TDM measurements,71.61%(222/310)achieved target concentrations.Multivariate analysis showed that CYP2C19 intermediate metabolite,daily dose of cyclosporine A(CSA),daily dose of VRCZ,creatinine(Cr)>97 μmol/L,albumin(Alb)and C-reactive protein(CRP)were independent influencing factors for VRCZ blood drug concentration non-compliance(Wald χ2=4.046～13.221,all P＜0.05).The nomogram demonstrated excellent discrimination,calibration(H-L goodness of fit test χ2=2.663,P=0.954),and clinical utility with net benefit across 0.05～0.96 risk thresholds.Conclusion The nomogram incorporating CYP2C19 gene phenotype,daily CSA dosing,daily VRCZ dosing,Cr levels,Alb and CRP provides a validated tool for optimizing VRCZ therapy in allo-HSCT recipients,enabling precision dosing strategies.

Objective To analyze the clinical and immunological characteristics of a rare case of CHARGE syndrome,we summarize the genotype and phenotype in the Chinese patient population,and explore the underlying immunopathogenic mechanisms.Methods Clinical data from a pediatric patient with CHARGE syndrome were collected and analyzed.A comprehensive analysis of the Chinese patient population was conducted.Gene analysis and immunological characterization were performed using flow cytometry,deep sequencing,and quantitative PCR.Results The proband was a premature female infant whose primary clinical manifestations included congenital heart disease,recurrent respiratory infections,respiratory failure,airway dysplasia,hearing impairment,and bilateral choroidal coloboma.Whole-exome sequencing revealed a de novo heterozygous nonsense mutation in the CHD7 gene,c.5122C＞T(p.Gln1708Ter),classified as pathogenic according to ACMG criteria.Immunological studies indicated impaired thymic output of T cells,significant alterations in the number and proportion of CD8+T cell subsets,increased apoptosis,and defective activation and production of key effector cytokines such as IFN-γ by CD8+T cells.However,no significant abnormalities were observed in peripheral lymphocyte proliferation.Conclusion CHARGE syndrome is a rare autosomal dominant genetic disorder primarily caused by mutations in the CHD7 gene.The main clinical features include ocular defects,cardiac disease,choanal atresia/cleft lip and palate,growth retardation,gonadal hypoplasia,and ear anomalies.This case study suggests that CHARGE syndrome is associated with abnormalities in the development,apoptosis,and effector functions of immune cells.

Objective To determine the pathogenicity of a novel mutation(c.109_111del)in DKC1 gene of an adult patient,and to analyze the clinical phenotype,immunophenotype and telomere length,so as to provide clues for early clinical identification and diagnosis.Methods The clinical data and peripheral blood samples of the patient were collected for genetic testing and family analysis.The lymphocyte subsets of the patient were detected by Flow cytometry,and the telomere length of the patient and healthy controls were detected by Flow-FISH.Results The main clinical manifestations of the patient were mucocutaneous triad,bone marrow failure and infection.The telomere length of lymphocytes in the patient was significantly shorter than that of healthy controls of the same age,and the absolute value and percentage of lymphocyte subsets were abnormal.Conclusion The clinical manifestations of DC patients are diverse.Flow-FISH detection of telomere length is helpful for early diagnosis of DC patients.

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 association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.

The American College of Cardiology/American Heart Association,in collaboration with other societies/associations,has issued"the 2023 Multimodality Appropriate Use Criteria for the Detection and Risk Assessment of Chronic Coronary Disease".This guideline aims to provide appropriate use criteria for the use of functional stress testing and anatomical diagnostic methods in the evaluation of known or suspected chronic coronary disease.The updated content of the guideline is of significant importance for guiding clinical practitioners in China to apply cardiovascular imaging techniques rationally,to detect chronic coronary disease patients at an early stage,and to conduct risk assessments accurately,thereby ensuring high-quality clinical management of patients with chronic coronary disease.

[Purpose]To analyze the changes in the incidence trend of thyroid cancer from 1990 to 2021,and to predict the future incidence from 2022 to 2030.[Methods]We collected data related to the incidence of thyroid cancer among Chinese residents from 1990 to 2021 in the Global Bur-den of Disease 2021(GBD 2021)study,analyzed the trend of thyroid cancer incidence using the Joinpoint regression model,and constructed a Bayesian age-period-cohort(BAPC)model to pre-dict the future incidence of thyroid cancer during the years of 2022-2030,based on the inci-dence data during the years of 1990-2021.[Results]From 1990 to 2021,the age-standardized incidence rate(ASIR)of thyroid cancer in China showed a fluctuating upward trend,and the ASIR of thyroid cancer in China in 2021 was 2.47/105,slightly lower than the global average(2.91/105)in the same year.In 2021,there were significant differences in new cases and incidence rate of thyroid cancer between men and women,with the incidence rate of women being higher than that of men.Among them,the number of new cases in women was 27 915,the crude incidence rate was 4.02/105,and the ASIR was 2.87/105;in men,the number of new cases was 20 189,the crude incidence rate was 2.77/105,and the ASIR was 2.11/105.Between 1990 and 2021,the increase in the number of new cases,the crude incidence rate,and the ASIR of men in China was much larger than that of women.The ASIR of thyroid cancer in both male and female showed an in-creasing trend,while the average annual percentage change(AAPC)in female was lower than that in male.There were significant gender differences in the age-specific incidence rates of thyroid cancer.In 2021,the incidence rate of women was higher than that of men in the Chinese population＜75 years old,whereas the incidence rate of men was higher than that of women in the population≥75 years old.From 1990 to 2021,the incidence rates of the Chinese male population aged 45～59 years old and ≥75 years old increased significantly;and the incidence rate of the Chinese fe-male popu-lation aged 50～74 years old increased significantly.Projections showed that the ASIR of overall,male and female standardized incidence rates in 2030 increased to 2.90/105,2.44/105 and 3.26/105 respectively.[Conclusion]The incidence rate of thyroid cancer in China is on the rise,with the incidence rate of women being higher than that of men,but the incidence rate of men has increased more than that of women,and the gap between the incidence rates is narrow-ing,and the peak age of incidence of men is mostly in the senior age group.