Background Carbendazim (CBZ), a widely used benzimidazole fungicide, has raised increasing concerns regarding the health risks associated with its residues. However, the toxic effects and associated mechanisms of CBZ on the skeletal system have not been reported. Objective To elucidate the effects of carbendazim on osteogenic differentiation and its underlying mechanisms. Methods MC3T3-E1 mouse pre-osteoblastic cells were treated with 1, 10, and 100 μmol·L⁻¹ CBZ for 24 h to examine cell viability, alkaline phosphatase (ALP) activity, bone nodule formation, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and nitric oxide synthase (NOS) activity. Transcriptomics was used to identify differentially expressed genes (DEGs) in osteoblasts exposed to CBZ. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were employed to analyze the potential biological pathways of DEGs. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to validate changes in gene and protein expression. Results Exposure to 10 and 100 μmol·L⁻¹ CBZ significantly reduced osteoblast viability, ALP activity, bone nodule formation, and NOS activity, while increasing intracellular ROS levels. CBZ at 100 μmol·L⁻¹ concentration significantly elevated MDA level (P < 0.05). The transcriptomic analysis revealed that 1 μmol·L⁻¹ CBZ treatment resulted in 385 significantly DEGs. The KEGG enrichment analysis revealed that CBZ significantly affects hormone regulation pathways (including parathyroid hormone, growth hormone, dopamine, and oxytocin), mitogen-activated protein kinase (MAPK) and cyclic GMP-dependent protein kinase G (cGMP-PKG) signaling pathways, focal adhesion and adherens junction, as well as the NOD-like receptor signaling pathway and the mRNA surveillance (NMD) pathway. The results of GSEA showed that CBZ significantly inhibited the bile acid metabolism and the Wnt/β-catenin pathway in osteoblasts. The validation results demonstrated that CBZ significantly suppressed the mRNA expression of Wnt3a and β-catenin, as well as the protein expression of Runx2 and Osterix in the Wnt/β-catenin pathway. Conclusion CBZ exposure exhibits potential skeletal toxicity, and its mechanism is through promoting oxidative stress, interfering with the Wnt/β-catenin pathway in osteogenic differentiation, thereby inhibiting the bone formation function of osteoblasts.

Objective: To explore the intervention effects of different exercise modalities on executive function in school aged children, providing references for formulating exercise prescriptions to promote school aged children executive function. Methods: A systematic literature search was conducted using PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP and CBM to identify studies on the effects of exercises on executive function in school aged children. The search period spanned from the database inception to August 2025. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. Network Meta analysis was performed using Stata 16.0. Results: A total of 51 studies involving 5 710 school aged children and seven modalities of exercises(control group,small ball sports,large ball sports,aerobic exercise,combined exercise,sport game,gymnastic and dance sports) were finally included. Network Meta analysis showed that, in terms of inhibitory control development of school aged children, small ball sports ( SMD =-0.98,95% CI =-1.32 to -0.64 ), large ball sports ( SMD =-0.64,95% CI =-0.91 to -0.36), and mixed sports ( SMD =-0.26,95% CI =-0.50 to -0.02]) were more effective than the control group; in terms of working memory, largeball sports ( SMD =-1.26,95% CI =-1.88 to -0.65) and small ball sports ( SMD =-0.91,95% CI =-1.64 to -0.19) were superior to the control group; in terms of improving cognitive flexibility, large ball sports ( SMD =-1.02,95% CI =-1.28 to -0.76), gymnastics and dance sports ( SMD =-0.80,95% CI =-1.21 to -0.40), and small ball sports ( SMD =-0.75,95% CI =-1.15 to -0.36) were more effective than the control group (all P <0.05). Surface under cumulative ranking curve(SUCRA) showed that small ball sports had the highest value (SUCRA=98.9%) in improving inhibitory control, while large ball sports achieved the highest score(SUCRA=92.6%) in enhancing working memory, and large ball sports also had the highest value(SUCRA=94.7%) in promoting cognitive flexibility. Conclusions For developing inhibitory control in school aged children, small ball sports are recommended as a priority. For enhancing working memory and cognitive flexibility, large ball sports are recommended.

Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

Objective: Patients with atherosclerotic cardiovascular disease (ASCVD) following percutaneous coronary intervention (PCI) are classified as very-high-risk individuals in cardiovascular disease (CVD) risk stratification. The distribution pattern of traditional Chinese medicine (TCM) syndromes in this patient population, as well as its association with blood lipid profiles and clinical prognosis, remains unclear. The present prospective cohort study aims to investigate these correlations, thereby providing insights to enrich the research fields. Methods: We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1, 2020 and December 31, 2022. Demographics and clinical characteristics, signs and symptoms defining each TCM syndrome, and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events (MACEs). We analyzed the correlation between TCM syndromes, blood lipid profiles, and MACEs, and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression. The analyses were based on detailed baseline and one-year follow-up data. Results: A per-protocol analysis was performed on 586 patients with complete data ultimately. During the one-year follow-up, 174 patients (29.69%) experienced a MACE. We performed statistical analyses on comorbidities, medication, and biochemical indicators across groups defined by TCM syndrome differentiation. When comparing different TCM syndromes, no significant differences were found in age, body mass index (BMI), history of revascularization, comorbidities, family history of CVD, smoking or drinking, or statin intensity (P > 0.05). Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol (TC, 5.27 ± 1.18 mmol/L, P < 0.001), triglyceride (TG, 1.96 ± 1.33 mmol/L, P = 0.008), low-density lipoprotein cholesterol (LDL-C, 3.35 ± 0.79 mmol/L, P < 0.001), and high-density lipoprotein cholesterol (HDL-C, 1.24 ± 0.81 mmol/L, P < 0.001) compared with those with other TCM syndromes combined. A multivariable logistic regression model was constructed to predict MACEs. The model included TCM syndrome type [with intertwined phlegm and blood stasis as a predictor, adjusted odds ratio (OR) = 1.413, 95% confidence interval (CI): 0.517 – 3.864, P = 0.501], age (adjusted OR = 0.97, 95% CI: 0.955 – 1.001, P = 0.057), male gender (adjusted OR = 0.698, 95% CI: 0.416 – 1.170, P = 0.173), TC (adjusted OR = 1.004, 95% CI: 0.513 – 1.965, P = 0.990), and LDL-C (adjusted OR = 5.825, 95% CI: 2.214 – 15.326, P < 0.001). This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients [the area under the receiver operating characteristic (ROC) curve (AUC) = 0.865, 95% CI: 0.816 – 0.914]. Conclusion The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C. The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters (TC and LDL-C) shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI, underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.

Objective: To explore the association between meat consumption and anxiety symptoms in first year junior high school students in Yunnan Province, and to provide theoretical support for preventing and relieving anxiety symptoms in junior high school students. Methods: From October to December 2022, a random cluster sampling method was used to select 8 500 first year junior high school students from 11 counties in Yunnan Province as the survey subjects for a questionnaire survey. The study used Food Frequency Questionnaire and the Chinese version of the Depression Anxiety Stress Scale-21 (DASS-21) to assess the meat consumption and anxiety symptoms of junior high school students.The distribution differences in anxiety symptoms among first year junior high school students with different demographic characteristics were analyzed statistically by using the Chi-square test,and the association between meat consumption and anxiety symptoms in students was analyzed by using a generalized linear model. Results: The detection rate of anxiety symptoms was 48.47%. After controlling for demographic variables and confounding factors, the consumption of livestock meat, poultry meat, processed meat, cured meat, barbecued meat and raw skin meat was statistically significant with anxiety symptoms ( β =-0.05, 0.04, 0.04, 0.08, 0.14, 0.17, all P <0.05). Stratified by ethnicity, The consumption of livestock meat, cured meat and barbecue was statistically correlated with anxiety symptoms in Han adolescents ( β =-0.07, 0.14, 0.22 ); the consumption of processed meat and raw skin meat was statistically correlated with anxiety symptoms in ethnic minority adolescents ( β =0.08, 0.18) (all P <0.05). Conclusions There is a statistical association between meat comsumption and the risk of anxiety symptoms in first year junior high school students in Yunnan Province. Guidance on meat consumption should be strengthened to prevent the occurrence of anxiety symptoms.

To investigate the clinical efficacy of neoadjuvant imatinib in the treatment of rectal gastrointestinal stromal tumor (GIST).

OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

ObjectiveTo investigate the effects of Jianpi Qinghua granules on blood glucose fluctuations in patients with newly diagnosed overweight/obese type 2 diabetes mellitus （T2DM） and Qi-Yin deficiency syndrome from the perspective of skeletal muscle mass and function， while providing new insights for the treatment of diabetes. MethodsThis study employed a randomized， double-blind， placebo-controlled design. A total of 110 newly diagnosed overweight/obese T2DM patients meeting the inclusion criteria were randomly assigned to either the traditional Chinese medicine （TCM） group （54 cases） or the control group （56 cases）. Patients in the TCM group received Jianpi Qinghua Granules， while those in the control group received a placebo. Both groups underwent dietary and exercise guidance. After 12 weeks of intervention， blood glucose fluctuations were assessed using the following parameters： time in the target blood glucose range （TIR）， mean daily blood glucose （MBG）， standard deviation of mean daily blood glucose （SDBG）， mean amplitude of glycemic excursions （MAGE）， coefficient of variation of blood glucose （CV）， glycated hemoglobin （HbA1c） achievement rate， fasting plasma glucose （FPG）， and 2 hour postprandial glucose （2 hPG）. Skeletal muscle mass was measured by dual-energy X-ray absorptiometry （DXA）， while skeletal muscle function was evaluated using a handheld dynamometer for distal muscle strength and a 5-time sit-to-stand test for lower limb function. Additionally， pancreatic islet function and TCM syndrome scores were analyzed. ResultsNo significant differences were observed in baseline data between the two groups before intervention， ensuring comparability. After treatment， compared to the control group， the TCM group showed a significant increase in TIR （P<0.01）. While the SDBG and CV decreased， and MBG and MAGE increased in the TCM group， these differences were not statistically significant. Notably， the TCM group exhibited significant reductions in 2 hPG （P<0.01） and HbA1c （P<0.05）， though the decrease in FPG was not statistically significant. The HbA1c achievement rate in the TCM group was significantly higher than that in the control group （χ²=45.498， P<0.01）. In terms of skeletal muscle mass and function， the TCM group demonstrated a significant increase in handgrip strength （P<0.01） and a significant reduction in the 5-time sit-to-stand duration （P<0.05）. However， although body fat percentage increased， leading to a decrease in skeletal muscle mass and the ratio of skeletal muscle to fat， these changes were not statistically significant. For pancreatic islet function， the TCM group showed significant reductions in fasting insulin （FINS） and homeostasis model assessment of insulin resistance （HOMA-IR） （P<0.01）. Additionally， the TCM syndrome score in the TCM group was significantly reduced （P<0.01）. ConclusionJianpi Qinghua granules may reduce blood glucose fluctuations in newly diagnosed overweight/obese T2DM patients with Qi-Yin deficiency syndrome by enhancing skeletal muscle function， improving pancreatic islet function， and ameliorating related TCM syndromes.

Hepatocellular carcinoma (HCC) develops within a profoundly immunosuppressive tumor immune microenvironment (TIME), which limits the efficacy of immunotherapy. Polarization of tumor-associated macrophages (TAMs) toward a pro-tumorigenic M2 phenotype is a major driver of immune escape. Ferroptosis, an iron-dependent regulated cell death program, intersects with hepatic iron metabolism and immune regulation and thus offers promising points of therapeutic intervention. This review systematically elucidates the mechanistic role of TAM ferroptosis in HCC immune evasion and highlights a “bidirectional regulation” intervention strategy grounded in the Traditional Chinese medicine (TCM) principle of “fortifying healthy qi and eliminating pathogens” (Fuzheng Quxie). This strategy employs “eliminating pathogens” (Quxie) approaches to exploit the metabolic vulnerability of M2-like TAMs and precisely induce their ferroptosis. Moreover, it utilizes “fortifying healthy qi” (Fuzheng) approaches to protect M1-like TAMs and CD8⁺ T cells from oxidative damage. This parallel “induction-protection” paradigm demonstrates the unique advantages of TCM in systemically remodeling TIME through multitarget synergistic actions. Accordingly, precision regulation of TAM ferroptosis based on the Fuzheng Quxie theory represents a promising integrative Chinese-Western medicine strategy for overcoming current bottlenecks in HCC immunotherapy, although its clinical translational potential warrants further validation.

Objective: To explore the longitudinal association between weight trajectories and physical fitness test composite scores among primary school students, so as to provide empirical evidence for school based weight management and physical health promotion. Methods: A total of 2 112 students from a primary school in Beijing who participated in physical fitness assessments annually from 2008 to 2023 were included and classified into different body weight trajectory groups based on body mass index (BMI) threshold: "normal/overweight-obese". Group based trajectory model was used to identify distinct weight trajectories. Generalized estimating equation and Cox regression were used to analyze the associations between weight trajectories and changes in physical fitness test scores, as well as event risks. Robustness checks were conducted. Results: The prevalence of overweight and obesity among primary school students was 26.50%. BMI showed a significant negative correlation with physical fitness composite scores ( r=-0.19, P <0.01). Four types of weight trajectories were identified: persistent normal group (64.5%, 1 362), persistent overweight- obese group (18.2%, 385), normal to overweight-obese group (14.0%, 296), and overweight-obese to normal group (3.3%, 69). Compared to the persistent normal group, both the normal to overweight-obese and persistent overweight-obese groups showed significantly higher risks of failing the physical fitness test ( HR =4.23, 4.60), and the speed of achieving excellent was slower ( HR = 0.52, 0.40) (all P <0.05). Robustness tests confirmed the stability of the findings. Conclusions Body weight trajectories have a long term impact on physical fitness performance among primary school students. Students with persistent or progressive overweight-obese trajectories have limited score improvement and a higher risk of failure; primary school students with persistent or progressive overweight and obesity should be a key focus.