ObjectiveTo investigate the contamination status of arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) in commercially available aquatic products in Shanghai and their distribution characteristics among different categories of aquatic products, and to assess the dietary exposure levels and non‑carcinogenic health risks of As, Cd, Pb, and Hg through aquatic product consumption among different age groups, so as to provide a scientific basis for food safety surveillance of aquatic products and dietary risk management for residents in Shanghai. MethodsFrom October to November 2021, a total of 90 aquatic product samples, including marine fish, freshwater fish, freshwater shrimp, marine crab, freshwater crab, and mollusks, were randomly collected from 16 districts of Shanghai. Sample pretreatment was performed according to GB 5009.268‒2016 (National Food Safety Standard—Determination of Multi‑elements in Foods). The concentrations of As, Cd, and Pb in aquatic products were determined by inductively coupled plasma mass spectrometry (ICP‑MS), and Hg was determined by direct mercury analyzer. Inorganic arsenic (iAs) was estimated as 3.5% of total As according to the method recommended by the European Food Safety Authority (EFSA). The contamination levels of As, Cd, Pb, and Hg in aquatic products were evaluated according to GB 2762‒2017 (National Food Safety Standard—Maximum Levels of Contaminants in Foods). A combined approach of point assessment and probabilistic assessment was applied to estimate the estimated daily intake (EDI) and non‑carcinogenic risk indicators—hazard quotient (HQ) and hazard index (HI)—for different age groups. ResultsThe detection rates of As and Hg were both 100.00% in all samples, while those of Cd and Pb were 74.44% and 25.56%, respectively. The arithmetic means (wet weight) of the four elements and estimated iAs were: As (1.432 9±3.736 5) mg·kg^-1, iAs (0.050 2±0.130 8) mg·kg^-1, Cd (0.082 5±0.197 8) mg·kg^-1, Pb (0.006 1±0.005 5) mg·kg^-1, and Hg (0.021 9±0.016 7) mg·kg^-1. According to the relevant maximum residue limits, 2 out of 7 mollusk samples (28.57%) and 3 out of 20 marine fish samples (15.00%) exceeded the limit for iAs, and 2 out of 8 marine crab samples (25.00%) exceeded the limit for Cd. The estimated daily intake (EDI, μg·kg^-1·d^-1, by body weight) of iAs, Cd, Pb, and Hg via aquatic product consumption varied among different age groups, with the highest levels observed in children aged 3‒4 years, decreasing gradually with age to the lowest level at 12 ‒ <15 years, with a slight rebound thereafter. The point assessment results showed that the HQs of iAs, Cd, Pb, and Hg ranged from 0 to 0.25, and the cumulative HI ranged from 0.27 to 0.48, all below 1, indicating a relatively low overall risk. The probabilistic assessment results revealed that under the high‑exposure scenario (P_97.5), the HQs of iAs (1.101‒1.281) and Cd (1.175‒1.366) exceeded 1 in children aged 3‒9 years, suggesting potential health risks, while the HQs of Pb and Hg were all below 1, indicating relatively lower risks. ConclusionHg and As are ubiquitously detected in commercially available aquatic products in Shanghai, while the detection rates of Cd and Pb are relatively low. The overall non-carcinogenic risk is at an acceptable level, but children aged 3‒9 years may have potential health risks from iAs and Cd under high-percentile exposure levels. It is recommended to strengthen the monitoring of toxic elements in key aquatic products such as marine fish, mollusks, and marine crabs, and to implement targeted dietary risk management measures for sensitive populations, including children.

This study delves into the mechanism of total flavone of Abelmoschus manihot(TFA) in treating ulcerative colitis(UC) and depression via inhibiting M1 polarization of macrophages and reshaping intestinal flora and glycerolphospholipid metabolism. The study established a mouse model of UC and depression induced by chronic restraint stress(CRS) and dextran sulfate sodium(DSS). The fecal microbiota transplantation(FMT) experiment after TFA intervention was conducted. Mice in the FMT donor group were modeled and treated, and fecal samples were taken to prepare the bacterial solution. Mice in the FMT receptor group were treated with antibiotic intervention, and then administered bacterial solution by gavage from mice in the donor group, followed by UC depression modeling. After the experiment, behavioral tests were conducted to evaluate depressive-like behaviors by measuring the levels of 5-hydroxytryptamine(5-HT) and brain-derived neurotrophic factor(BDNF) in the hippocampus of mice. The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the brain and colon tissue of mice were also measured, and the polarization status of macrophages was evaluated by measuring the mRNA levels of CD86 and CD206. 16S ribosomal RNA(16S rRNA) sequencing technology was used to analyze changes in the intestinal flora of mice. Wide target lipidomics was used to detect serum lipid metabolite levels in mice after FMT,and correlation analysis was conducted between lipids and differential intestinal flora significantly regulated by TFA. In vitro experiments, representative glycerophospholipid metabolites and glycerophospholipid inhibitors were used to intervene in Raw264.7 macrophages, and the mRNA levels of TNF-α,IL-6,IL-1β,CD86,and CD206 were detected. The results showed that TFA and FMT after intervention could significantly improve depressive-like behavior and intestinal inflammation in mice with UC and depression, significantly downregulate pro-inflammatory cytokines and CD86 mRNA expression in brain and colon tissue, inhibiting M1 polarization of macrophages, and significantly upregulate CD206 mRNA expression, promoting M2 polarization of macrophages. In addition, the high-dose group had a more significant effect. After TFA intervention, FMT significantly corrected the metabolic disorder of glycerophospholipids in mice with UC and depression, and there was a significant correlation between differential intestinal flora and glycerophospholipids. In vitro experiments showed that glycerophospholipid metabolites, especially lysophosphatidylcholine(LPC),significantly upregulated pro-inflammatory cytokines and CD86 mRNA expression, promote M1 polarization of macrophages, while glycerophospholipid inhibitors had the opposite effect. The results indicate that TFA effectively treats depression and UC by correcting intestinal flora dysbiosis and reshaping glycerophospholipid metabolism, thereby inhibiting M1 polarization of macrophages.
Animals ; Mice ; Gastrointestinal Microbiome/drug effects* ; Abelmoschus/chemistry* ; Macrophages/metabolism* ; Colitis, Ulcerative/immunology* ; Flavones/administration & dosage* ; Male ; Depression/genetics* ; Glycerophospholipids/metabolism* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL

Objective: To investigate the seroepidemiological characteristics of hepatitis B among outpatients in medical institutions in Jiaxing City, Zhejiang Province, so as to provide a reference for formulating region-specific hepatitis B prevention and control strategies. Methods: From April to June 2024, outpatients were selected as study subjects from sentinel medical institutions in Jiaxing City. Information such as gender and age was collected. Venous blood samples were obtained and serological markers including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb), and hepatitis B core antibody (HBcAb) were tested. Positive rates of hepatitis B virus (HBV) serological markers were analyzed by genders and ages. Results: A total of 1 468 outpatients were included, among whom 721 were males (49.11%) and 747 were females (50.89%). The mean age was (46.41±19.66) years. The positive rates of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb were 7.29%, 44.75%, 1.84%, 23.50%, and 42.03%, respectively. The HBcAb positive rate in males was significantly higher than in females (46.05% vs. 38.15%, P<0.05), while no statistically significant gender differences were observed in the positive rates of other four HBV serological markers (all P>0.05). Except for HBsAb, the positive rates of the other four HBV serological markers showed statistically significant differences across different age groups (all P<0.05). Pairwise comparisons results showed that the HBsAg positive rates in age groups of 20-<40 years and 40-<60 years were 9.48% and 9.57%, respectively, which were higher than those in age groups of <20 years (1.43%) and ≥60 years (2.75%) (all P<0.05). A total of 17 HBV serological marker patterns were observed, among which the proportion of all markers negative was the highest, at 39.65%. The proportions of "small three positive" (HBsAg+, HBeAb+, HBcAb+) and "large three positive" (HBsAg+, HBeAg+, HBcAb+) patterns were 4.77% and 1.50%, respectively. Among HBsAg-positive individuals, the proportions of the "small three positive" pattern across age groups were 0, 45.45%, 90.00%, and 81.82%, while those of the "large three positive" were 0, 36.36%, 5.00%, and 0, with statistically significant differences across age groups (both P<0.05). Conclusions The positive rate of HBsAg among outpatients in medical institutions in Jiaxing City is relatively high, with a notable proportion of individuals showing either no immunity or non-response to vaccination. It is recommended to strengthen hepatitis B immunization efforts among the population aged 20-<60 years, and to enhance monitoring and interventional treatment for "small three positive" and "large three positive" patterns.

Objective:To investigate the efficacy and safety of glofitamab in the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 patients with relapsed/refractory DLBCL who were treated with glofitamab in Sichuan Provincial People's Hospital from March 2024 to October 2024 were retrospectively analyzed. All patients received glofitamab monotherapy. Dose escalation was required in the first course, and glofitamab at a dose of 30 mg was administered from the second to the 12th course. The general data, clinical manifestations, laboratory examination results, Eastern Cooperative Oncology Group (ECOG) performance score, previous treatment history, therapeutic effect after medication and adverse reactions were collected.Results:Among 11 patients, there were 8 males and 3 females, with the median age [ M ( Q1, Q3)] of 60 (51, 76) years; 1 case was primary central nervous system DLBCL. The median number of prior treatment lines was 3 (2, 3) lines, and 6 cases received ≥3 lines of therapy; 1 case was double DLBCL and 3 cases was complicated with p53 mutations. The median follow-up time was 5 months (2-7 months). After treatment of the median number of glofitamab, 3 cases achieved complete remission, among which 1 case successfully bridged to autologous hematopoietic stem cell transplantation; 1 case had the stable disease and 7 cases achieved partial remission. Grade 1-2 adverse events included mild leukopenia in 3 patients, mild anemia in 4 patients, thrombocytopenia in 1 patient, and lymphopenia in 8 patients. Grade 3 hematologic adverse events included thrombocytopenia in 1 patient and severe lymphopenia in 1 patient. Non-hematological toxicities included mild rash in 1 patient, grade 1 liver dysfunction in 3 patients and inflammatory factor storm in 4 patients. No medication stop or deferral was found in patients due to severe adverse events. Conclusions:Glofitamab demonstrates a high response rate in the treatment of relapsed/refractory DLBCL, with manageable adverse events and a favorable safety.

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

The activation of Keap1-Nrf2 signaling pathway is an important mechanism for cells to resist oxidative stress.Under oxidative stress,Keap1 is affected by post-translational modification(PTM)such as glutathione,alky-lation and S-sulfhydrylation,which weakens its binding to Nrf2,leading to Nrf2 accumulation,nuclear translocation and the expression and transcription of downstream detoxification and antioxidant defense proteins.The PTM of Keap1 is involved in the regulation of a variety of oxidative stress-related diseases such as cancer,Parkin-son's disease and atherosclerosis.For example,alkylation inhibits abdominal aortic aneurysm formation,methylation promotes innate resistance of breast cancer,and S-sulfhydrylation improves atherosclerosis,which pro-vides a theoretical basis for finding new drug targets and biomarkers.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective To investigate the characteristics of changes in pain-anxiety-depression-fatigue symptom clusters and their possible associated factors in adolescents with acute lymphoblastic leukemia(ALL)during early chemotherapy.Methods A prospective longitudinal study was conducted from Nov 2019 to Oct 2021,enrolling newly diagnosed adolescent ALL patients from 5 tertiary or pediatric specialty hospitals in Shanghai,Zhejiang Province,Sichuan Province,Anhui Province and Guangdong Province.Patient-reported pain,anxiety,depression,and fatigue were collected at five time points within the first nine weeks of chemotherapy using the PROMIS Pediatric-25 instrument.Latent profile analysis(LPA)and latent transition analysis(LTA)were applied to explore the latent classes of symptom clusters,their transition probabilities over time,and possible risk or protective factors associated with class membership.Results A total of 134 ALL cases were enrolled,and symptom clusters at all the 5 time points(T1-T5)were consistently classified into three groups of mild,moderate and severe symptoms.The severe symptoms group accounted for the largest proportion at each time point(54.5%,59.7%,66.4%,49.3%,and 47.0%,respectively),while the mild and moderate symptoms groups showed an initial decline followed by an increase.Among participants,40.2%maintained the same symptom status,and 77.4%experienced at least one episode of severe symptom status during the trajectory.Religious affiliation(T5)and family monthly income>5 000 Yuan(T2,T4 and T5)served as protective factors against severe symptoms.Higher baseline fatigue(T1)was associated with membership in the severe symptoms group at subsequent time points.Conclusion Pain-anxiety-depression-fatigue symptoms in adolescents with ALL during early chemotherapy can be categorized into mild,moderate and severe symptoms with dynamic transitions over time.Higher baseline fatigue was associated with increased risk of severe symptoms,whereas higher family income and religious affiliation appeared protective effects.

OBJECTIVE To explore the application value of a diagnostic model based on machine learning and SHAP in the diagnosis of severe pneumonia caused by adenovirus infection in children.METHODS A total of 562 children with adenovirus infection who were admitted to Wuhan Third Hospital from Mar.2023 to Apr.2024 were selected and divided into a non-pneumonia group(n=236)and a pneumonia group(n=326).The pneumonia group was further divided into a training set(n=245)and a validation set(n=81)at a ratio of 3∶1.The training set was further categorized into a severe group(n=90)and a non-severe group(n=155)based on the severity of pneumonia.M ultivariate logistic regression analysis was used to identify the risk factors for severe pneumonia in children with adenovirus infection,and collinearity diagnosis was performed.Receiver operating characteristic(ROC)curves were used to validate the predictive performance of the model in both the training and validation sets,and the optimal model was selected.The optimal predictive model was interpreted using SHAP.RESULTS Compared with the non-pneumonia group,the pneumonia group had a high proportion of children aged＜2 years,with cough,wheezing,pulmonary consolidation,pleural effusion,mixed infections and allergic history,as well as long hospital stays and fever duration(P＜0.05).After univariate analysis and collinearity diagnosis to exclude confounding factors,the length of hospital stay(OR=1.112),fever duration(OR=1.964),wheezing(OR=2.430),pulmonary consolidation(OR=2.546),mixed infections(OR=2.617)and LDH level(OR=1.613)were identified as risk factors for severe pneumonia in children with adenovirus infection(P＜0.05).Among the eight machine learning models constructed based on these risk factors,the gradient boosting machine(GBM)model demonstrated the best performance in predicting severe pneumonia in children with adenovirus in-fection,with area under the curve(AUC)of 0.796 and 0.785 in the training and validation sets,respectively.SHAP analysis revealed that the top four contributing characteristics were LDH level,wheezing,fever duration and pulmonary consolidation.CONCLUSIONS The GBM model exhibits optimal performance in predicting the risk of severe pneumonia in children with adenovirus infection.Among the predictive characteristics,LDH level,wheezing,fever duration and pulmonary consolidation are significant,providing valuable reference for clinical di-agnosis and treatment.