This study aims to explore the clinicopathological and immunological characteristics of Talaromyces marneffei (TM) infection in patients with acquired immunodeficiency syndrome-related diffuse large B-cell lymphoma (AIDS-DLBCL), and to analyze the risk factors and prognostic impact. This study was designed as a retrospective cohort study, clinical data of 73 patients with AIDS-DLBCL admitted to the First Hospital of Changsha from January 2020 to December 2021 were collected and analyzed, and the patients aged 26 to 84 years, including 63 males and 10 females.Patients were divided into a TM infection group (n=17) and a non-TM infection group(n=56) based on the presence or absence of TM infection.The clinical and pathological characteristics as well as therapeutic effects of the two groups of patients were compared using the χ2 test and Fisher's exact test. Survival curves were plotted using the Kaplan-Meier method, and the association between AIDS-DLBCL specific variables and TM infection was analyzed using the binary logistic regression model. The results showed that a total of 73 patients with AIDS-DLBCL were included. Among them, 23.3% had TM infection(17/73). The histopathological examination of biopsy tissues showed that TM appeared as yeast-like round or oval spores under special staining, some of which were sausage-shaped or joint-like, with a septum in the middle, and existed within or outside macrophages. Comparative analysis between the two groups showed that the proportions of patients with HIV-RNA>200 copies/ml [88.24% (15/17) vs. 58.93% (33/56), χ2=4.260, P=0.039], CD4⁺ T cell count<50 cells/μl [41.18% (7/17) vs. 8.93% (5/56), χ2=9.553, P=0.004], occult blood (OB) positivity [47.06% (8/17) vs. 17.86% (10/56), χ²=5.173, P=0.023], and Mycobacterium tuberculosis (MTB) positivity [29.41% (5/17) vs. 3.57% (2/56), Fisher's exact test, P=0.006] were significantly higher in the TM infection group than in the non-TM infection group, with statistically significant differences between the groups (all P<0.05). Survival curve analysis showed that the 2-year overall survival rate of the TM infection group was significantly lower than that of the non-TM infection group [52.94% (9/17) vs. 92.85% (52/56), χ²=17.670, P<0.001]. The binary logistic regression model analysis showed that CD4+T cell count<50 cells/μl (OR=8.29, 95%CI:1.47-46.81), positive tuberculosis (OR=17.70, 95%CI:2.21-148.01), and positive occult blood (OR=5.19, 95%CI:1.14-23.57) were risk factors affecting the occurrence of TM infection in AIDS-DLBCL. In conclusion, CD4⁺ T cell count<50 cells/μl, occult blood positivity, and tuberculosis positivity may be risk factors for TM infection in patients with AIDS-DLBCL.
Objective: To explore the association between feeding styles and early developmental trajectories of infants aged 6-12 months. Methods: This prospective cohort study recruited 367 mother-infant dyads from a multicenter longitudinal study in China on feeding behavior and early development of infants aged 0-12 months between July 2019 and October 2024. Information about infants and their parents was collected through questionnaires. The weight of infants at 3 months of age was evaluated by performing physical examinations. Feeding styles of infants at 3 months of age were evaluated using the Infant Feeding Style Questionnaire (IFSQ), and the early development Z-scores of infants at 6, 9, and 12 months of age were evaluated by using the Caregiver Reported Early Development Instrument (CREDI) simplified version. The group-based trajectory model was used to identify potential categories of Z-score trajectories in early infant development. Multivariate logistic regression was performed to examine the association between feeding styles and early development Z-score trajectory. Results: Among the 367 mothers surveyed, 327 (89.1%) were aged ≤35 years at baseline, and 305 (83.1%) had a bachelor's degree or above. There were 188 male infants (51.2%), with an average weight of 6.4±0.8 kg at 3 months of age. In terms of feeding styles at 3 months of age, 163 infants (44.4%) were subject to high-frequency food restriction, 159 (43.3%) to high-frequency forced feeding, and 121 (33.0%) to high-frequency food-based soothing. About 121 infants (33.0%) had caregivers with high sensitivity to infant hunger and satiety cues, and only 37 (10.1%) had caregivers with close attention during infant feeding. Among infants aged 6-12 months, two potential early development Z-score trajectories were identified, with 304 (82.8%) in the "average early development" and 63 (17.2%) in the "optimal early development". Multivariate logistic regression showed that compared with infants who were forced to eat at low frequency at 3 months of age, frequent forced feeding reduced the likelihood of infants being in the "optimal early development" at 6-12 months of age (OR=0.48, 95%CI:0.26-0.91). Compared with infants who received less attention during feeding at 3 months of age, infants who received close attention were more likely to achieve "optimal early development" (OR=3.10, 95%CI:1.30-7.35). Conclusion: Responsive feeding styles may be associated with the optimal developmental trajectory of infants.
Objective: To develop a prediction model for colorectal cancer liver metastasis (CRLM) using machine learning algorithms based on routine clinical laboratory data. Methods: A retrospective case-control study was performed on 5 026 patients with colorectal cancer admitted to Qilu Hospital of Shandong University from January 2019 to August 2023. Clinical information and 70 routine laboratory indicators at admission were collected. Patients were randomly divided into training and validation sets in a 7∶3 ratio. Feature selection was performed stepwise using LASSO regression followed by multivariate logistic regression. A random forest (RF) prediction model was constructed in the training set. The model performance was comprehensively evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, decision curve analysis (DCA), calibration curve, and Brier score, and further validated in the validation set. SHapley Additive exPlanations (SHAP) analysis was used to interpret the feature importance of the final model. Results: 11 laboratory indicators were screened to develop an RF predictive model, including AFP, CEA, CA19-9, ADA, HDL-C, LDH, Cys C, GLDH, Hcy, PT, and lymphocyte ratio. The AUC of the RF model, CEA, CA19-9, and combined detection of the two markers was 0.867, 0.737, 0.738, and 0.786, respectively. Delong test revealed that the predictive performance of the RF model was superior to that of the other detection methods (all P<0.05). Model interpretation using the SHAP algorithm revealed that carcinoembryonic antigen, carbohydrate antigen 19-9, and other indicators were key predictors of CRLM. Conclusion: An interpretable machine learning model is developed for the early prediction of liver metastasis and personalized treatment regimens in colorectal cancer patients through the effective integration of clinical laboratory data, providing valuable clinical decision support to clinicians and improving patient prognosis.
Objective: To investigate the impact of the hsdS gene on the phenotypic characteristics and transcriptomic expression profiles of Mycoplasma pneumoniae (MP). Methods: This study is an experimental study. A total of 20 clinical MP strains were isolated from the clinical respiratory samples from the children with pneumonia in Shanghai Children's Hospital, between December 2023 and December 2024. MP strains were selected and divided into the multi-hsdS homologous group (MHG, n=10) and the oligo-hsdS homologous group (OHG, n=10) based on the number of hsdS homologous genes. The two groups were compared in terms of biofilm formation capacity, growth rate, morphological polarization of macrophages, and inflammatory cytokine secretion levels using independent-sample t-tests or Mann-Whitney U tests. Differentially expressed genes were analyzed by transcriptome sequencing and validated by RT-qPCR. Results: Compared with the OHG group, the MHG group exhibited significantly enhanced biofilm formation capacity (OD590: 0.33±0.06 vs. 0.28±0.05, t=3.364, P=0.001), accelerated growth rate (OD430/OD560: day 5: 4.03±1.51 vs. 2.81±1.80, t=2.852, P=0.042, day 6: 7.35±0.49 vs. 6.02±1.62, t=3.018, P=0.026), and an increased proportion of morphologically polarized macrophages (49.8%±15.7% vs. 29.6%±9.3%, t=2.657, P=0.026). Transcriptome sequencing revealed that the overall expression of hsdS homologous genes was upregulated in the MHG group (54.87±75.99 vs. 21.78±35.36, t=3.058, P=0.003), along with upregulation of topJ, MPN_RS00155, ftsZ, thyA, and multiple ATP synthase subunits (P<0.05). Except for MPN_RS03435, the expression levels of the remaining seven genes in the MHG group were significantly higher than those in the OHG group (topJ: t=3.144, P=0.014; MPN_RS00155: t=2.927, P=0.019; ftsZ: t=3.172, P=0.013; thyA: t=2.429, P=0.041; atpH: t=3.379, P=0.010; atpG: t=4.204, P=0.003; MPN_RS03405: t=2.368, P=0.045). Conclusion: The enhanced of hsdS homologous genes is closely associated with biofilm formation capacity, growth rate, and ability to induce morphologically macrophage polarization of MP strains, and upregulates the transcriptional expression of multiple phenotype-related genes.
In 2024, the overall prevalence of malnutrition (including wasting, overweight, and obesity) among children and adolescents aged 6-18 years in Zhejiang Province was 34.80%, with the prevalences of mild wasting, moderate-to-severe wasting, overweight, and obesity being 4.54%, 3.30%, 14.25%, and 12.72%, respectively. The highest prevalences of moderate-to-severe wasting, overweight, and obesity were 4.74% (aged 6-8 years), 16.43% (aged 15-18 years), and 14.89% (aged 9-11 years), respectively. The prevalences of mild wasting, moderate-to-severe wasting, overweight, and obesity were all higher in boys than in girls (5.11% vs. 3.91%, 3.56% vs. 3.01%, 16.67% vs. 11.60%, 15.84% vs. 9.30%, all P<0.001). The prevalence of obesity was lower among urban students than among rural students (12.05% vs. 13.30%, P<0.001), while the prevalence of overweight was higher among middle school students than among primary school students (15.88% vs. 12.84%, P<0.001). From 2005 to 2024, the prevalence of wasting among children and adolescents aged 6-18 years in Zhejiang Province showed a trend of initial increase, followed by a decrease, and then a rebound [Annual Percentage Change (APC) values were 1.88, -3.87, and 7.45 for the periods 2005-2008, 2009-2020, and 2021-2024, respectively]. The prevalence of overweight and obesity exhibited a continuous upward trend, though its growth rate gradually slowed (APC values were 4.80, 3.12, and 0.12 for the periods 2005-2013, 2014-2020, and 2021-2024, respectively).
Objective: To investigate the expression and function of Zeste 12 homolog (SUZ12) in hepatocellular carcinoma (HCC), and to preliminarily explore its biological role and underlying molecular mechanisms in HCC. Methods: This cell-based experimental study was conducted at the Basic Laboratory of the General Hospital of Southern Theater Command of the PLA from June 2024 to June 2025. The mRNA and protein expression levels of SUZ12 in HCC tissues and their correlations with clinicopathological features were analyzed using The Cancer Genome Atlas (TCGA). The prognostic impact of SUZ12 on HCC patients was evaluated using the K-M plotter database. SUZ12 overexpression and knockdown models were established in human hepatocellular carcinoma cells (HepG2). Transfection efficiency was verified by quantitative real-time polymerase chain reaction (qPCR) and Western blot. The effects of SUZ12 on HCC cell proliferation, invasion, and migration were assessed via Cell Counting Kit-8 assay (CCK-8), colony formation assay, and Transwell assay. The interaction between SUZ12 and enhancer of Zeste homolog 2 (EZH2) was validated by Co-Immunoprecipitation (Co-IP). Western blot was further used to preliminarily examine the effects of SUZ12 on the protein expression levels of H3K27me3 and CDKN1A. Statistical analyses were performed using two independent-sample t-tests. Results: In HCC tissues, SUZ12 mRNA levels were significantly higher than those in normal liver tissues (TPM=7.644 vs. 4.643, t=-6.648, P<0.001), and SUZ12 protein expression levels were also significantly elevated (Z-score=0.004 vs.-1.621, t=-9.815, P<0.001). The mRNA expression level of SUZ12 showed an increasing trend with higher clinical stage (normal: 4.643; stage Ⅰ: 7.071; stage Ⅱ: 7.085; stage Ⅲ: 8.677 TPM,H=36.700, P<0.001) and pathological grade (normal: 4.643; grade 1: 5.589; grade 2: 7.032; grade 3: 8.586 TPM, H=38.200, P<0.001). In the CCK-8 assay, the cell viability value in the SUZ12 overexpression group was higher than that in the control group; the relative absorbance at 450 nm on day 1(0.370±0.020 vs. 0.379±0.010, t=0.376, P=0.725), day 2 (0.477±0.016 vs. 0.370±0.069, t=-4.391, P=0.005), day 3 (0.900±0.022 vs. 0.816±0.024, t=-6.577, P=0.001), day 4 (1.601±0.017 vs. 1.390±0.026, t=-2.477, P=0.048). The cell viability value in the SUZ12 knockdown group was lower than that in the control group; the relative absorbance at 450 nm on day 1 (0.277±0.005 vs. 0.287±0.001, t=1.737, P=0.133), day 2 (0.344±0.002 vs. 0.377±0.006, t=4.677, P=0.010), day 3 (0.643±0.006 vs. 0.720±0.006, t=4.142, P=0.012), day 4 (1.065±0.015 vs. 1.210±0.031, t=8.941, P<0.001). In the colony formation assay, the number of colonies formed in the SUZ12 overexpression group was significantly higher than that in the control group [(775.000±51.884) colonies vs. (429.333±16.756 )colonies, t=-6.340, P=0.003]; the number of colonies decreased in the knockdown group [(150.666±4.055) colonies vs. (272.666±7.172) colonies, t=13.917, P<0.001]. In the Transwell assay, the invasion ability [(329.000±33.291) cells vs. (229.333±12.732) cells, t=-4.564, P=0.010] and migration ability [(325.333±7.310) cells vs. (217.333±1.732) cells, t=-14.120, P<0.001)] were significantly enhanced in the SUZ12 overexpression group compared to the control group; the invasion ability [(269.000±19.467) cells vs. (374.000±22.500) cells, t=3.529, P=0.024] and migration ability [(163.333±8.412) cells vs. (272.333±19.220) cells, t=6.194, P=0.020] were significantly weakened in the SUZ12 knockdown group compared to the control group. Western blot results suggested that high expression of SUZ12 downregulated the protein expression level of CDKN1A. Conclusion: SUZ12 high expression is associated with malignant biological behaviors of HCC cells. The SUZ12/EZH2/CDKN1A axis may represent a potential therapeutic target for patients with advanced HCC.
Objective: To explore the functional role of RAD51AP1 protein targeting and binding to mRNA in human lung adenocarcinoma A549 cells and its effect on cell proliferation and apoptosis. Methods: In vitro cytological and molecular biological experiments were conducted in the Surgical Research Laboratory of the General Hospital of Ningxia Medical University from January 2024 to September 2025.The expression of RAD51AP1 protein in lung adenocarcinoma tissue was analyzed by Immunohistochemistry(IHC). A549 cell with RAD51AP1 overexpression and knockdown was constructed by Lentiviral transfection, and divided into the RAD51AP1-shRNA group and the RAD51AP1-Over group. Flow cytometry was used to detect cell proliferation and apoptosis. RIP-seq combined with RNA-seq was performed to identify the mRNA molecules targeted by RAD51AP1 protein. The mRNA and protein expression levels of FASN, MUC5B, and RAD51AP1 were detected by RT-qPCR and Western blot, respectively. Actinomycin D assay to detect the RNA stability of FASN, MUC5B, and RAD51AP1 mRNA. Nuclear translocation assay to detect the nuclear import of RAD51AP1 protein. In this study, for normally distributed measurement data, comparisons between two groups were performed using independent samples t-test, while comparisons among multiple groups were conducted using one-way analysis of variance. Count data were presented as frequencies or percentages, and inter-group comparisons were made using the chi-square test. Results: Immunohistochemistry showed that the RAD51AP1 protein is highly expressed in lung adenocarcinoma. Flow cytometry results showed that cell proliferation was significantly increased (27.30±0.72 vs. 47.13±1.04, t=27.13, P<0.000 1)and apoptotic was significantly decreased (9.95±0.87 vs. 3.50±0.41, t=11.62, P<0.000 1)in the RAD51AP1-Over group, while the opposite trends were observed in the RAD51AP1-shRNA group. RIP-seq and RNA-seq results showed that FASN, MUC5B, and RAD51AP1 may be the target mRNA molecules of RAD51AP1 protein. RT-qPCR results showed that compared to the control group, MUC5B mRNA expression was significantly decreased in RAD51AP1-Over group(0.83±0.18 vs. 0.22±0.09, t=5.29, P<0.01), FASN mRNA expression levels was no significant difference in both the RAD51AP1-shRNA and RAD51AP1-Over groups(0.96±0.10 vs. 0.92±0.07, t=0.62;vs. 0.94±0.03, t=0.38;P>0.05). RAD51AP1 mRNA expression showed significant differences consistent with silencing and overexpression(1.02±0.08 vs. 0.15±0.12, t=10.38;vs. 27.51±1.98, t=23.22;P<0.01).Western blot results were consistent with those of RT-qPCR. Actinomycin D assay showed that, compared with the control group, the half-life of MUC5B mRNA was significantly down-regulated in both the RAD51AP1-shRNA and RAD51AP1-Over groups (13.72±0.17 vs. 12.54±0.17, t=8.50;vs. 11.64±0.29, t=10.66;P<0.05). No significant difference was observed in the half-life of FASN mRNA among the groups (8.10±0.19 vs. 7.63±0.23, t=2.75;vs. 7.22±0.60, t=2.43;P>0.05). The half-life of RAD51AP1 mRNA was significantly decreased in the RAD51AP1-shRNA group (10.67±0.52 vs. 5.66±0.12, t=1.93, P<0.05), while no significant difference was found in the RAD51AP1-Over group (10.67±0.52 vs. 9.96±0.37, t=16.21, P>0.05). Nuclear translocation assay showed that the nuclear fluorescence intensity was significantly increased in the RAD51AP1-Over group compared with the Control group (1.00±0.08 vs. 2.24±0.14, t=13.08, P<0.05). Conclusion: Overexpression of RAD51AP1 promoted cell proliferation and inhibited apoptosis, whereas the opposite effects were observed in its knockdown. Furthermore, RAD51AP1 exerts a non-canonical bidirectional regulatory effect on the stability of MUC5B mRNA, whereas no conventional stability regulation was observed for FASN or RAD51AP1's own mRNA, suggesting that it may primarily function through other mechanisms (such as DNA repair or transcriptional regulation) in this cellular system.
Objective: To understand the influencing factors of the second dose of varicella vaccine for children aged 1-12 years in 10 provinces of China. Methods: In December 2022, a multistage random sampling method was employed to recruit children aged 1-12 years who had received one dose of varicella vaccine and their guardians from 180 vaccination clinics in 10 provinces of China. Questionnaire surveys were conducted to collect information on children's characteristics, guardians' demographic characteristics, and vaccination status. Chi-square test and multivariate logistic regression were used to identify independent factors associated with receipt of the second dose of varicella vaccine. Compared with children who had received only one dose, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated. Results: A total of 1 947 questionnaires were included, with 1 081 (55.5%) who received two doses of varicella vaccine. Multivariate logistic regression showed that children whose guardians were aged 30 years or older (OR=1.220, 95%CI: 1.007-1.479), whose guardians were medical professionals (OR=1.457, 95%CI:1.054-2.014), and whose annual household income was 100 000 yuan or more (OR=1.739, 95%CI:1.395-2.168) had a higher proportion of receiving the second dose of varicella vaccine. Conclusion: Among children aged 1-12 years in 10 provinces of China who had received only one dose of varicella vaccine, the proportion of receiving the second dose remains suboptimal. Guardians' age, occupation, and annual household income might be the main influencing factors.
Objective: To investigate the associations of the triiodothyronine (T3) to thyroxine (T4) ratio (T3/T4), thyroid-stimulating hormone (TSH), and free T3 to free T4 ratio (FT3/FT4) with the risk of diabetes among elderly individuals aged 65 years and older in longevity areas of China. Methods: Data were drawn from the 2021 cross-sectional survey of the Healthy Ageing and Biomarkers Cohort Study (HABCS), which enrolled 5 795 participants across 18 longevity areas in China. Plasma concentrations of FT3, FT4, T3, T4, and TSH were determined using chemiluminescence immunoassay, and fasting blood glucose (FBG) was measured via the hexokinase method. Diabetes mellitus was defined as an FBG≥7.0 mmol/L and/or self-reported physician-diagnosed diabetes. Multivariable logistic regression models were applied to evaluate the independent associations of FT3/FT4, T3/T4, and TSH with diabetes. Additionally, restricted cubic splines (RCS) were utilized to visualize and analyze the exposure-response relationships. Results: The age of the 5 795 study participants was (85.25±11.56) years; 56.3% were female, and the prevalence of diabetes was approximately 16.1%. The M (Q1, Q3) values for FT3/FT4, T3/T4, and TSH were 0.27 (0.24, 0.30), 0.020 (0.017, 0.022), and 2.12 (1.34, 3.44) mIU/L, respectively. Multivariable logistic regression analysis showed that, after adjusting for confounding factors, compared with the Q4 group of FT3/FT4 ratio, the risk of diabetes was higher in the Q1 (OR=2.02, 95%CI: 1.61-2.54), Q2 (OR=1.72, 95%CI: 1.39-2.13), and Q3 groups (OR=1.37, 95%CI: 1.11-1.70); compared with the Q4 group of T3/T4 ratio, the risk of diabetes was higher in the Q1 (OR=2.16, 95%CI: 1.71-2.73), Q2 (OR=1.70, 95%CI: 1.37-2.12), and Q3 groups (OR=1.51, 95%CI: 1.22-1.86) (all P<0.001). RCS analysis revealed that FT3/FT4 (P overall<0.001, P nonlinear=0.846) and T3/T4 (P overall<0.001, P nonlinear=0.492) exhibited linear inverse associations with diabetes. Conclusion: Lower FT3/FT4 and T3/T4 ratios are linearly and inversely associated with an increased risk of diabetes among the population aged 65 years and older across 18 longevity areas in China.
Objective: To investigate the antibody persistence and influencing factors of the simplified two-dose and standard three-dose hepatitis B vaccine (HepB) among people aged 15-40 years after 20 years of primary immunization. Methods: In November 2003, a total of 1 994 healthy people aged 15-40 were randomly selected from 20 villages in Jiyang County, Jinan City, Shandong Province. Venous blood samples were collected from 3-5 ml of people who tested negative for hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs), and anti-hepatitis B core antibody (anti-HBc). A total of 850 people were included in the study. The study randomly assigned 428 people to the "0-1-6" immunization program group and 422 people to the "0-6" immunization program group, and administered primary immunization to people using 10 μg HepB according to the corresponding program. 629 people completed full immunization and underwent blood sampling and anti-HBs testing one month after immunization. Blood samples were collected at 1 month, 12 years (2015), and 20 years (2023) after primary immunization, and solid-phase radioimmunoassay (SPRIA) or chemiluminescence particle immunoassay (CMIA) were used to detect anti-HBs, HBsAg, and anti-HBc. Simultaneously, a questionnaire survey was conducted, and information on birth date, gender, vaccination time, HepB immunization history, smoking history, alcohol consumption history, chronic disease history, and family members' hepatitis B infection history were collected during the baseline survey and follow-up survey. The generalized estimation equation (GEE) was used to analyze the main effects, interaction effects, and influencing factors of anti-HBs seropositive rates and geometric mean concentration (GMC). Results: A total of 304 people were followed up at 1 month, 12 years (2015), and 20 years (2023) after primary immunization, with 50.99% (155 people) in the "0-1-6" immunization program group. In 2003, 2015, and 2023, the seropositive rates of anti-HBs in the "0-1-6" immunization program group were 94.19% (95%CI: 89.26%-97.31%), 74.19% (95%CI: 66.56%-80.88%), and 69.68% (95%CI: 61.79%-76.79%), respectively. The seropositive rates of anti-HBs in the "0-6" immunization program group were 87.25% (95%CI: 80.80%-92.14%), 55.03% (95%CI: 46.68%-63.18%), and 51.01% (95%CI: 42.70%-59.28%), respectively. In 2003, 2015, and 2023, the anti-HBs GMC of the "0-1-6" immunization program group were 268 (95%CI: 200-359) mIU/ml, 34 (95%CI: 26-46) mIU/ml, and 37 mIU/ml (95%CI: 27-51), respectively. The anti-HBs GMC of the "0-6" immunization program group were 121 (95%CI: 87-168) mIU/ml, 13 (95%CI: 9-18) mIU/ml, and 15 (95%CI: 11-20) mIU/ml, respectively. The main effects analysis of GEE showed that there were statistically significant differences in the anti-HBs seropositive rates and GMC between the "0-1-6" immunization program group and the "0-6" immunization program group (both P<0.001). Compared with 2003, the anti-HBs seropositive rate and GMC were lower in 2015 and 2023 (both P<0.001). There was no interaction effect between the seropositive rate of anti-HBs and the follow-up time of anti-HBs GMC and the immunization program (both P>0.05). The multivariate analysis of GEE showed that compared with the "0-1-6" immunization program group and the 2003 baseline, the "0-6" immunization program group (OR=0.45, 95%CI: 0.30-0.68, P<0.001) had lower anti-HBs seropositive rates in 2015 and 2023 (OR=0.17, 95%CI: 0.12-0.25, P<0.001; OR=0.14, 95%CI: 0.10-0.20, P<0.001). Compared with the "0-1-6" immunization program group, baseline in 2003, and without chronic disease history, people in the "0-6" immunization program group (β=-0.83, 95%CI:-1.19--0.47, P<0.001) had lower anti-HBs GMC in 2015 and 2023 (β=-2.15, 95%CI:-2.37--1.93, P<0.001; β=-2.04, 95%CI:-2.27--1.80, P<0.001), and those with chronic disease history (β=0.55, 95%CI: 0.02-1.08, P=0.043). Conclusion: Compared with those receiving three-dose HepB, people receiving two-dose HepB have lower anti-HBs seropositive rates and GMC. Seropositive rates are associated with immunization program and follow-up duration, while the anti-HBs GMCs are associated with immunization program, follow-up duration, and chronic disease history.
Objective: Investigating the impact of combined exposure to cold spells and heavy pollution on circulatory disease mortality in the population. Methods: Daily population mortality, atmospheric fine particulate matter (PM2.5), and meteorological data were collected from 70 districts/counties in the Beijing-Tianjin-Hebei region and surrounding areas from 2013 to 2018. Cold spells were defined by daily mean temperature (<10th percentile) and duration (≥2 days), while heavy pollution events were defined by PM2.5 daily mean concentration (>75 μg/m³,>115 μg/m³,>150 μg/m³) and duration (≥2 days). Further, three overlapping combined exposure events were constructed. Based on this, three scenarios of combined exposure to cold spells and heavy pollution events were defined: Scenario A involved overlapping cold spell and heavy pollution periods; Scenario B featured a standalone heavy pollution event occurring within 7 days after a cold spell ended; Scenario C featured a standalone cold spell event occurring within 7 days after a heavy pollution event ended. A distributed lag nonlinear model was used to analyze the impact of each district/county's combined events on mortality risk. A meta-analysis was conducted to calculate cumulative relative risk (CRR) and attributable deaths. Subgroup analyses were also conducted. Results: During the cold season (November to March) from 2013 to 2018, the mean daily temperatures and PM2.5 concentrations across all districts/counties were (3.1±5.8) ℃ and (98.58±78.19) μg/m³, respectively, with an average of (6±5) daily circulatory disease deaths. The CRR (95%CI) of combined exposure to cold spells and heavy pollution was 1.35 (1.14-1.60), higher than that of exposure to cold spells [1.14 (1.09-1.20)] or heavy pollution [1.08 (1.00-1.16)] alone. However, the exposure and lag-response relationships differed across various combined scenarios. At a cumulative lag of 21 days, the CRR values (95%CI) for circulatory disease mortality associated with combined scenarios A, B, and C were 1.24 (1.17-1.32), 1.12 (1.01-1.23), and 1.17 (1.11-1.22), respectively. Subgroup analysis revealed that the increased risk associated with combined events was primarily observed in specific disease subcategories such as ischemic heart disease and cerebrovascular disease. Conclusion: Combined cold spells and heavy pollution exposure events increase the risk of multiple circulatory disease deaths in the population. Compared with other combined scenarios, higher risks may be associated when cold spells and heavy pollution overlap in time.
To analyze the subtypes, epidemiological characteristics, and drug resistance of HIV-1 strains among newly diagnosed HIV-1-infected individuals in Huai'an City from 2021 to 2023 based on molecular transmission networks. The in-house assay was used to amplify the pol gene fragment of the virus and complete sequencing, genotyping, and analysis of drug resistance mutations. The HIV-1 molecular transmission network was constructed, and the multivariate logistic regression was used to analyze the association between demographic and sociological characteristics and network-clustering transmission. The majority of 422 infected individuals was males (84.60%), aged over 50 years (38.86%), married (48.10%), those with a junior high school education or below (59.48%), non-students (94.79%), and infected through men who have sex with men (MSM) transmission routes (54.50%). The predominant HIV-1 subtypes were CRF07_BC (33.41%, 141/422) and CRF01_AE (28.20%, 119/422). The network entry rate was 34.36% (145/422), and three active transmission clusters were identified. The multivariate logistic regression revealed that females (OR=2.256, 95%CI:1.321-3.853), those aged ≥50 years (OR=1.812, 95%CI:1.133-2.899), and those with the education level of junior high school or below (OR=2.250, 95%CI:1.306-3.900) were independent risk factors for entering the molecular transmission network. Nineteen drug-resistant cases were detected among network participants and distributed across 12 transmission clusters, of which 8 drug-resistant clusters had cross-district transmission characteristics. In summary, the 422 newly reported HIV-1 infections in Huai'an City from 2021 to 2023 are mainly transmitted by middle-aged and elderly males with low education levels and through MSM as the major transmission route. The strains are mainly CRF07_BC and CRF01_AE, and gender, age, and educational level are risk factors affecting the entry of infected individuals into the molecular transmission network. Some transmission clusters exhibit drug resistance and cross-district characteristics.
Objective: To investigate the association between urinary personal care products (PCPs) level and the risk of diabetes among adults aged 18-79 years. Methods: Data was derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 911 adults. Information on general demographic characteristics, behavioral habits, and dietary frequency was collected through questionnaire surveys and physical examinations. Fasting venous blood and midstream random urine samples were collected to measure fasting blood glucose and urinary personal care product levels. Multivariable logistic regression models were used to examine the associations between urinary PCP levels and diabetes prevalence. Subgroup analyses were further conducted according to age, sex, residence, and history of hair dyeing or perming. Results: A total of 911 participants were included in this study, including 458 females (50.3%), 319 residents aged 19-39 years (35.0%), and 456 rural residents (50.1%). The concentrations of the three parabens were 23.30 (20.73, 26.19), 2.00 (1.74, 2.30), and 2.74 (2.34, 3.22) μg/g creatinine, respectively. Multivariable logistic regression analysis showed that, after adjusting for potential confounding factors, urinary ethyl paraben (EtP) levels were positively associated with diabetes prevalence (OR=1.17, 95%CI: 1.02-1.34, P=0.025). Subgroup analyses further showed that the positive association between urinary EtP levels and diabetes prevalence was stronger among females (OR=1.25, 95%CI: 1.02-1.54, P=0.029) and individuals with a history of hair dyeing or perming (OR=1.29, 95%CI: 1.05-1.59, P=0.016). Conclusion: Urinary ethyl paraben exposure was positively associated with an increased risk of diabetes among Chinese adults, with women and individuals with a history of hair dyeing or perming potentially representing susceptible subpopulations warranting further attention.
This study collected fecal and blood samples from diarrhea patients at three hospitals in Jiamusi City between 2015 and 2023. After isolation and identification, 98 Salmonella strains were obtained, and whole-genome sequencing and annotation analysis were performed on these strains. The results showed that the 98 strains were classified into 23 serotypes, with Salmonella Enteritidis being the most common (44.89%, 44/98). The isolates exhibited resistance to streptomycin, ampicillin, tetracycline, and nalidixic acid. The multidrug resistance rate was 52.04% (51/98), and the mutation rate of the quinolone resistance-determining region was 57.14% (56/98). A total of 48 resistance genes belonging to 10 categories were detected, with the aminoglycoside resistance gene aac(6')-Iaa being the most prevalent (94.89%). Both the core genome multilocus sequence typing analysis and the phylogenetic analysis based on single nucleotide polymorphisms demonstrated a correlation with serotype, and the isolates were predominantly Salmonella Enteritidis. Virulence factors were predominantly associated with secretion systems and fimbrial adherence. In conclusion, in Jiamusi City, Salmonella Enteritidis is the dominant serovar, multidrug-resistant Salmonella is prevalent, aminoglycoside resistance genes are highly prevalent, chromosomal mutations dominate the resistance mechanism, genetic relatedness exists among the isolates, and virulence genes are abundant, indicating strong pathogenic potential.
DNA methylation represents one of the most prevalent and significant epigenetic modifications in humans, playing a crucial role in numerous physiological and pathological processes within the human body. It demonstrates considerable potential as a novel disease biomarker. DNA methylation testing involves diverse sample types and complex procedures, with no unified standards currently established for its workflow. Consequently, developing a consensus on sample processing and detection techniques for DNA methylation holds significant value for advancing technological development, clinical translation, and application in this field. This consensus document, jointly authored by the Laboratory Medicine Committee of the Chinese Association of Integrative Medicine, the Molecular Diagnostics Group of the Chinese Society of Laboratory Medicine of Chinese Medical Association, and the Precision Medicine Committee of the Beijing Association of the Integrating of Traditional and Western Medicine, synthesizes the perspectives and expertise of specialists of laboratory medicine and pathology. The present document provides detailed guidance on key aspects such as the definition of DNA methylation, sample collection and pre-processing, nucleic acid extraction and conversion, methylation detection, and reporting of results. Fourteen consensus statements have been distilled from this comprehensive framework.
To screen out potential ligands of Agglutinin-like sequence protein 3 (ALS3) with anti-adhesion from the candidate drug library. To clarify the antibacterial and anti-biofilm activities of proanthocyanidins (PAC) and conduct a preliminary exploration of their metabolomics mechanisms. From January to December in 2023, at the Laboratory Department of Guiyang Maternal and Child Health Hospital,using ALS3 as the target protein, the molecular docking virtual screening method was adopted to screen out ALS3 inhibitors with potential resistance to biofilm formation. The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of PAC for Candida albicans were determined by the micro-liquid-based dilution method, and the time-growth curve was plotted to explore the antibacterial activity of PAC for Candida albicans. The XTT[2, 3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] staining method was used to explore the formation of Candida albicans biofilms by PAC and its dispersal effect on the formation of mature biofilms within 24 hours. The metabolites of Candida albicans after the action of PAC were identified by liquid chromatography-mass spectrometry. Multivariate analysis (principal component analysis and partial least squares discriminant analysis) and univariate analysis (t-test) were used to screen differential metabolites to preliminarily explore the anti-biofilm mechanism of PAC. The results showed that a total of 69 compounds were obtained through Glide's three-level screening (SP, XP, HTVS). Based on the criteria of (1) docking scores better than diazepam and (2) excluding antibiotics, PAC compounds with excellent scores and relatively promising pattern binding were obtained. The MIC of PAC is 256 μg/ml, and the MFC is 1 024 μg/ml, showing a time-dose dependence. The concentration of PAC with a 50% inhibition rate on Candida albicans biofilm is 256 μg/ml(one-way analysis of variance, F=15.92,P<0.001). When the concentration reaches 1 024 μg/ml, PAC can inhibit 80% of Candida albicans biofilm formation(One-way analysis of variance, F=15.92,P<0.001).For mature Candida albicans biofilms, when the PAC concentration reaches 1 024 μg/ml, it exhibits a dispersal effect on approximately 40% of the biofilm.(One-way analysis of variance, F=5.01,P=0.002). The results of non-targeted metabolomics indicated that compared with the untreated control group, the total number of differential metabolites of Candida albicans under the action of PAC was 350, among which 119 were up-regulated and 231 were down-regulated. The significantly changed differential metabolites include: 5-hydroxypiperidinic acid, Rhodamine 123, allantoin, indolebutyric acid, thiamine, etc.The main metabolic pathways enriched by differential metabolites are: global and overview maps, carbohydrate metabolism, membrane transport systems, lipid metabolism, cofactor and vitamin metabolism, nucleotide metabolism, and amino acid metabolism. In conclusion,it is feasible to use ALS3 as the target and a virtual screening method to search for the hit compounds of anti-Candida albicans biofilms. PAC was revealed to be an inhibitor targeting ALS3 in Candida albicans, and its anti-biofilm mechanism is associated with disturbances in energy metabolism, nucleic acid synthesis, membrane structure disruption, and enhanced oxidative stress.
Objective: To screen for novel candidate serum biomarkers of colorectal cancer (CRC) using serum proteomics, and to evaluate the value of combining them with conventional tumor markers to construct a multivariable diagnostic model for the non-invasive auxiliary diagnosis of CRC. Methods: This study adopted a retrospective case-control design and consecutively enrolled patients with colorectal diseases and healthy individuals undergoing routine health examination at the Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, between August 2023 and August 2024. Candidate protein markers were screened by four-dimensional data-independent acquisition (4D-DIA) mass spectrometry and subsequently validated by enzyme-linked immunosorbent assay (ELISA) in 623 participants (267 with CRC, 256 healthy controls, and 100 with colorectal polyps). On this basis, a machine learning diagnostic model incorporating multiple variables was constructed, and a nomogram was generated. Between-group differences were compared using non-parametric methods such as the Kruskal-Wallis test, and diagnostic performance was evaluated and compared using the area under the ROC curve (AUC) in combination with the DeLong test. Results: A total of 140 differentially expressed proteins were identified by 4D-DIA proteomic analysis, and stepwise screening selected three candidate markers-lipopolysaccharide-binding protein (LBP), inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3), and C-X-C motif chemokine ligand 7 (CXCL7)-for the large-sample validation cohort. In the validation cohort of 623 participants, the serum concentrations of LBP, ITIH3, and CXCL7 in the CRC group were all significantly higher than those in the healthy control and colorectal polyp groups (Kruskal-Wallis H values of 161.77, 232.62, and 126.89, respectively; all P<0.001), and their AUCs for discriminating CRC from all non-tumor participants were 0.797, 0.857, and 0.760, respectively, all superior to CEA (AUC=0.711) and CA19-9 (AUC=0.606). The three-protein combination of ITIH3, CXCL7, and LBP further improved performance, achieving an AUC of 0.905 for discriminating CRC from all non-tumor participants; in stage I CRC, the AUCs of LBP, ITIH3, and CXCL7 for discriminating CRC from all non-tumor participants were 0.701, 0.792, and 0.789, respectively, all superior to CEA (AUC=0.594) and CA19-9 (AUC=0.537), and the ITIH3+CXCL7 combination further reached an AUC of 0.853. In the independent test set, the seven-variable logistic regression model achieved an AUC of 0.919 (95%CI: 0.872-0.955) for discriminating all-stage CRC from all non-tumor participants, significantly outperforming the CEA+CA19-9 reference model (AUC=0.704; DeLong P<0.001); for stage I CRC, the model yielded AUCs of 0.879, 0.882, and 0.870 for distinguishing stage I CRC from all non-tumor participants, healthy controls, and benign diseases, respectively, all significantly superior to the CEA+CA19-9 reference model (corresponding AUCs of 0.651, 0.664, and 0.645; DeLong P=0.003, 0.003, and 0.012, respectively). The model was well calibrated (Hosmer-Lemeshow test χ²=6.31, P=0.613); decision curve analysis showed that its net benefit exceeded that of the CEA+CA19-9 model across threshold probabilities of 0.05-0.50, with this advantage being more pronounced in early-stage CRC. A nomogram derived from the model showed that the total points contributed by ITIH3, LBP, and CXCL7 (90.8) exceeded those of CEA and CA19-9 (1.3). Conclusion: The combined detection of LBP, ITIH3, and CXCL7 together with conventional markers can improve auxiliary diagnostic performance for CRC, particularly early-stage CRC.
Objective: To analyze the diagnostic accuracy of upper gastrointestinal lesions and the influencing factors among the pathologists in the Upper Gastrointestinal Cancer Screening Program in Rural China from 2019 to 2023. Methods: The assessment questionnaires were created using pathological images of esophageal and gastric lesions. The "Early Diagnosis and Treatment" application was used as an examination platform. The multivariate ordinal logistic regression was used to analyze the factors influencing the examination score grade of esophageal and gastric lesions. Results: A total of 1 565 pathologists participated in the assessment, with an average age of (39.49±8.17) years and 39.74% being males. The average examination score for esophageal and gastric lesions was 71.29±11.49 and 78.47±11.72, respectively. The multivariate ordinal logistic regression revealed that pathologists with postgraduate degree (OR=1.87, 95%CI:1.30-2.70), undergraduate degree (OR=1.60, 95%CI:1.17-2.17), professional work with experience of 10-<15 years (OR=1.41, 95%CI:1.02-1.97), and participating in the program for ≥2 years (OR=1.90, 95%CI:1.53-2.36) had higher diagnostic accuracy of esophageal lesions, respectively. Pathologists with postgraduate degree (OR=2.09, 95%CI:1.67-2.61), undergraduate degree (OR=1.60, 95%CI:1.34-1.91), attending physicians (OR=1.26, 95%CI:1.07-1.48), participating in the program for ≥2 years (OR=1.20, 95%CI:1.06-1.35), and from western areas (OR=1.19, 95%CI:1.01-1.40) had higher diagnostic accuracy of gastric lesions, respectively. Conclusion: The pathologists basically acquire diagnostic skills of upper gastrointestinal lesions in the Upper Gastrointestinal Cancer Screening Program in Rural China. Education level, professional title, duration of the career, duration of participating in the program, and location are associated with the diagnostic accuracy of the pathologists.
Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants, young children and older adults. Based on global RSV genomic surveillance data, this review systematically summarizes the geographic distribution, seasonal epidemic patterns, and long-term evolutionary trends of RSV, with particular emphasis on the sustained circulation and evolutionary mechanisms of dominant genotypes such as ON1 in RSV-A and BA9 in RSV-B. Current evidence indicates that RSV transmission dynamics are tightly coupled with viral evolution. The G gene evolves relatively rapidly and contains multiple positively selected sites, suggesting an important role in immune escape and population adaptation. In recent years, changes in social behavior patterns and population immunity have further disrupted the seasonal rhythm of RSV and may have influenced the spread of dominant genotypes. Under routine respiratory infectious disease surveillance, strengthened genomic monitoring and integration of multi-source data are needed to improve early warning of abnormal RSV epidemics and variant-associated risks, thereby providing prospective evidence for protecting high-risk populations and informing public health decision-making.
In January 2026, the U.S. Department of Agriculture and the Department of Health and Human Services jointly released the"Dietary Guidelines for Americans 2025-2030"(hereinafter referred to as the"new guidelines"). The core focus of these guidelines has shifted from nutrient limits to overall food quality; they advocate"enjoying real food,"take a clear stand against highly processed foods, increase the recommended protein intake, recommend full-fat dairy products, and simplify information dissemination strategies. While these changes have attracted widespread attention, they have also sparked significant controversy, including contradictions between visual presentations and written recommendations, the absence of quantitative limits, and a lack of transparency in the revision process. This article systematically interprets the major changes and scientific rationale behind the new guidelines, analyzes related academic controversies, compares the dietary guidelines of China and the United States, and evaluates their implications for China's nutrition policy from the dual perspectives of their value as a reference and their potential risks, taking into account the dietary structure, metabolic characteristics, and nutritional status of the Chinese population.
