Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

Background Long working hours, as a common risk factor for occupational stress, is closely related to the occurrence of depressive symptoms. Understanding how long working hours affect occupational stress and depressive symptoms will inform occupational health interventions. Objective To quantify the impact of long working hours exposure on occupational stress and depressive symptoms among Internet industry employees, translate black-box outputs into actionable insights, and demonstrate the value of interpretable machine learning for early-warning occupational-health surveillance. Methods A dataset was derived from a cross-sectional survey involving 2866 internet industry employees in China. This survey was part of the project Risk Assessment Of Long Working Hour Exposure And Its Adverse Health Effects, conducted by the National Institute for Occupational Health and Poisoning Control, Chinese Center for Disease Control and Prevention, from 2021 to 2023. Working hours, occupational stress and depressive symptoms were quantified with a set of structured questionnaires including the Core Occupational Stress Scale and the Patient Health Questionnaire. Pairwise associations were screened by Mantel tests and variance-inflation factors. Key predictors identified through feature selection were fed into six machine-learning risk-prediction models. Visual interpretation was provided by feature importance, Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME), while directed causal effects and intervention impacts of prolonged working hours exposure on occupational stress and depressive symptoms were dissected with causal explanation of features techniques. Results The positive rates of occupational stress and depressive symptoms among internet employees were 12.9% and 77.8% respectively. Twelve core features for occupational stress and nine for depressive symptoms were retained after selection. After these features were supplied to six predictive algorithms and evaluated on five metrics, the Light Gradient Boosting Machine (LGBM) achieved the highest accuracy—0.89 for occupational stress and 0.79 for depressive symptoms on the hold-out test set. The feature-importance rankings converged on fatigue accumulation and life satisfaction as dominant drivers for both outcomes, whereas weekly working hours and daily overtime emerged as the principal exposure-related predictors. The SHAP summary plots revealed that longer weekly hours and daily overtime systematically elevated the probability of occupational stress. The causal feature explanation further quantified that ascending one category in weekly working hours increased the probability of occupational stress by 7.04%. Conclusion Exposure to long working hours is associated with both occupational stress and depressive symptoms among internet industry employees. Interpretable machine-learning frameworks translate these associations into transparent, defensible drivers, enabling precise identification of the pivotal factors and their interplay. This evidence base equips occupational-health practitioners with actionable insights for designing targeted prevention and intervention strategies.

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Liquiritigenin(LG)is a flavone of pharmacological importance,however,its application potential is severely limited due to its poor water solubility.LG could be disassociated slightly in water to form phenolate anion,therefore,better solubilization effect is expected by inclusion with cationic cyclodextrins(CCDs).In this work,four kinds of CCDs modified with amino groups at the primary face were synthesized,and their solid inclusion complexes with LG were successfully prepared by preparing their saturated solutions.The formation of the solid inclusion complexes was confirmed by scanning electron microscopy(SEM)and powder X-ray diffraction(PXRD),and their supramolecular binding behavior in solution was studied using multiple techniques.A 1∶1 inclusion stoichiometry of inclusion complexation was defined using Job plot by ultraviolet-visible(UV-vis)spectroscopy,and their binding stability constants(Ks)were determined as 2862.77,3494.70,6521.85 and 9599.48 L/mol using UV-vis spectroscopic titration,far more superior to that of nativeβ-CD(Ks=236.79 L/mol).This indicated that the amino side chains on CCDs could actively participate in the inclusion complexation through anion-cation interactions,significantly strengthening the host-guest binding between CCDs and LG.The inclusion modes were further elucidated based on proton and two-dimensional rotating-frame overhauser enhancement spectroscopy(2D-ROESY)nuclear magnetic resonance(NMR)experiments and molecular docking.Water solubility of LG was dramatically promoted up to 4.9 mg/mL,which was 70-fold higher than that of native LG.This study could draw inspiration for the binding and solubilization of phenols such as flavones by design of cationic macrocyclic molecules.

Follicular Helper T Cells(TFH)are a specialized subset of CD4+T cells that predominantly lo-calize within lymphoid follicles.These cells play a crucial role in facilitating B cell proliferation,differentia-tion,and antibody production,thereby thereby serving as a pivotal component of the adaptive immune re-sponse against infections.Given the significant function of TFH cells in regulating humoral immunity,they have become a focal point in the research of infectious diseases and related vaccine development in recent years.This review summarizes the surface markers of T follicular helper(Tfh)cells,their differentiation reg-ulatory mechanisms,and the latest research progress of Tfh cells in SARS-CoV-2 infection and vaccine stud-ies.It aims to provide new theoretical foundations and research insights for optimizing the design of SARS-CoV-2 vaccines and enhancing the cross-protection ability against SARS-CoV-2 variants.

Objective:To explore the technique methods and clinical application value of β-electrode (a plasma needle shape electrode) assisted laparoscopic repair of complex vesicovaginal fistula (VVF).Methods:Clinical data of one patient with complex VVF admitted to Chinese PLA General Hospital in April 2025 was retrospectively analyzed. A 36-year-old female presented with urinary leakage 2 months after hysterectomy. Computed tomography urography excluded ureterovaginal fistula. Cystoscopy revealed a 2 cm fistula on the posterior bladder wall with both ureteral orifices adjacent to the fistula edge. The procedure involved two steps: first, transurethral β-electrode pretreatment was performed to protect the ureteral orifices and create a passage from the bladder to the abdominal cavity. Then, laparoscopic separation, suture closure of the fistula, and omental flap coverage were conducted.Results:Total operation time was 180 min (the time of β- electrode operation was 30 min) with intraoperative estimated blood loss of 50 mL. The catheter was removed 3 weeks postoperatively, and the patient voided well without leakage during 4-month follow-up.Conclusions:β- electrode assisted laparoscopic repair of complex VVF have the advantage of precise manipulation, minimal invasion and rapid recovery. No similar technique have been reported domestically or internationally. This technique provides a new approach for the treatment of complex VVF.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndrome manifestations and syndrome types in advanced colorectal cancer(CRC),and to mine out the medication rules and the core prescriptions of traditional Chinese medicine in the treatment of advanced CRC as well as to observe the clinical efficacy of the core prescriptions.Methods From January 2022 to March 2024,the first-visit medical records of the outpatients and inpatients of advanced CRC admitted to the Department of Oncology,Suzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine were collected.The data of clinical information and prescriptions were input to the Traditional Chinese Medicine Inheritance Support System(TCMISS)V2.5.And then the TCM syndrome manifestations and syndrome types,medication frequency and attributes of Chinese herbal medicines were analyzed.A core prescription(Jianpi Huashi Prescription)was obtained after association rule analysis and cluster analysis.The core prescription was used for the treatment of CRC,and the cure rate and total effective rate after 4,8 and 12 weeks of treatment were compared.Moreover,the changes of TCM syndrome score,Karnofsky Performance Status(KPS)score and quality of life score evaluated with Functional Assessment of Cancer Therapy-Colorectal(FACT-C)were observed before and after treatment.Results(1)The data mining showed that a total of 143 prescriptions were included in this study,involving 214 Chinese herbal medicines.The medicines were usually sweet and warm in flavor and nature,and mainly had the meridian tropism of the spleen and liver meridians.The association rule analysis yielded 14 core drug combinations and 7 new candidate prescriptions,and the herbal combination of Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine and Citri Reticulatae Pericarpium had the highest support(94 times)with a confidence of 95.92%.The results of frequency analysis showed that the top five TCM syndrome manifestations were poor appetite,poor sleep at night,weakness and fatigue,loose stools,and abdominal distension.The top three TCM syndrome types were spleen deficiency with predominant dampness syndrome,spleen-qi deficiency syndrome,and spleen-kidney yang deficiency syndrome,and the syndrome element of spleen deficiency had the highest frequency.Apriori correlation analysis and entropy clustering yielded a core prescription(Jianpi Huashi Prescription),which was composed of Citri Reticulatae Pericarpium,Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine,crude Astragali Radix,Atractylodis Macrocephalae Rhizoma,Coicis Semen,Galli Gigerii Endothelium Corneum,Corydalis Rhizoma,Spatholobi Caulis,Sargentodoxae Caulis,Sclerotium Poriae Pararadicis and Albiziae Cortex.(2)Clinical research showed that after 8 and 12 weeks of treatment,the markedly effective rates for TCM syndromes were 25.87%(37/143)and 50.35%(72/143)respectively,and the total effective rates were 60.14%(86/143)and 79.02%(113/143)respectively,which were significantly higher than 13.99%(20/143)and 41.96%(60/143)after 4 weeks of treatment,and the differences were statistically significant(P＜0.05 or P＜0.01).Moreover,the scores of TCM syndromes,KPS scores and FACT-C scores after 12 weeks of treatment were significantly improved compared with those before treatment,and the differences were statistically significant(P＜0.05 or P＜0.01).Conclusion Patients with advanced CRC usually have the syndrome of spleen deficiency,often complicated with cancer-toxin,phlegm,dampness,blood-stasis and other pathogens.Jianpi Huashi Prescription can enhance the clinical efficacy of CRC in the treatment of stage IIIB-IV,decrease the TCM syndrome score,and improve the patient's performance status and quality of life.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the effect of changes in metabolic syndrome status and persistence on carotid plaque risk.Methods:This retrospective cohort study analyzed individuals who underwent routine health check-ups at the health management center of the Second Affiliated Hospital of Dalian Medical University from 2014 to 2023. Participants with at least three carotid ultrasound records meeting the inclusion criteria were classified into 4 groups based on changes in metabolic status: persistently metabolic health, transitioning from metabolic health to unhealth, transitioning from metabolic unhealth to health, and persistently metabolic unhealth. The cumulative incidence of carotid plaque in these groups was compared. A Cox proportional risk model was used to evaluate the relationship between changes in metabolic syndrome status, the number of metabolic syndrome components, and the risk of carotid plaque development. Restricted cubic spline analysis was applied to explore the association between changes in individual metabolic syndrome components and carotid plaque risk.Results:Compared to the persistently metabolic health group, the persistent unhealth group had the highest risk of developing carotid plaque( HR=1.35, 95% CI 1.05-1.74, P=0.021), followed by those who transitioned from metabolic health to unhealth and those who improved from metabolic unhealth to health. Furthermore, the risk of carotid plaque increased progressively with the number of metabolic syndrome components. Restricted cubic spline analysis revealed a nonlinear relationship between fasting blood glucose change and carotid plaque risk, while systolic blood pressure, diastolic blood pressure, waist circumference, triglycerides, and high-density lipoprotein-cholesterol showed a linear dose-response relationship with carotid plaque. Conclusions:The change of metabolic syndrome is associated with the risk of developing carotid plaque, and maintaining metabolic health, recovering from metabolic syndrome, or minimizing the number of metabolic syndrome components may be effective strategies to prevent carotid plaque formation.