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.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

ObjectiveTo investigate the effect of solute carrier family 7 member 5 (SLC7A5) inhibitor JPH203 on renal fibrosis induced by unilateral ureteral obstruction in mice. MethodsSixteen SPF male C57BL/6 mice were randomly divided into the control group and the experimental group, with 8 mice in each group. The mouse model of renal fibrosis was established by unilateral ureteral obstruction. From the third day after surgery, the mice in the control group were intraperitoneally injected with phosphate-buffered saline (PBS) for 11 consecutive days, and the injection dose was 200 μL/d. Mice in the experimental group received intraperitoneal injection of JPH203 (50 mg/kg) every day for 11 days. On day 14, the mice were euthanized, then the kidney tissues were obtained. Hematoxylin and eosin (HE) staining was used to assess renal tissue damage, Masson staining was used to evaluate collagen fiber deposition in the extracellular matrix, and immunohistochemistry was used to detect the levels of fibroblast activation markers α-smooth muscle actin (α-SMA) and collagen type Ⅰ (COL-Ⅰ) in kidney tissues. Western blotting was further performed to measure the expression levels of SLC7A5 and transforming growth factor-β1 (TGF-β1), as well as the phosphorylation levels of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway-related molecules. Real-time quantitative PCR was used to verify changes in the mRNA levels of SLC7A5, α-SMA, and COL-Ⅰ in kidney tissues. ResultsCompared with the control group, the experimental group showed reduced destruction of renal tissue structure and a significantly lower pathological injury score (P<0.05). Additionally, collagen deposition in the extracellular matrix was decreased, and the percentage of collagen fiber area was significantly reduced (P<0.001) in the experimental group. The levels of fibroblast activation markers α-SMA and COL-Ⅰ were significantly lower in the experimental group (both P<0.001). The expression levels of SLC7A5 and TGF-β1 were also significantly decreased (P<0.001), and the phosphorylation levels of mTORC1 signaling pathway-related proteins 4E-BP1 and mTORC1 were significantly reduced (P<0.001). Real-time quantitative PCR confirmed that the mRNA levels of SLC7A5, α- SMA, and COL-Ⅰ in kidney tissues were significantly lower in the experimental group (P<0.001). ConclusionJPH203 may inhibit the progression of renal fibrosis in mice by suppressing SLC7A5 expression, regulating the mTORC1 signaling pathway, and altering fibroblast activation status.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

OBJECTIVE To establish a Chinese drug-related problem （DRP） classification system applicable to pharmacist-led pharmaceutical care in China， providing pharmacists with an effective and practical tool for pharmaceutical care. METHODS A multi-stage process was employed to construct the DRP classification system， including literature review and analysis， comparison of existing classification systems， refinement of classification items and framework development， two rounds of standard case validation， expert discussion， and system revision. The Fleiss′ kappa test was used to calculate the consistency coefficient κ， assessing the reliability of pharmacists participating in evaluating the classification system. An electronic questionnaire comprising six items was employed to evaluate the system’s applicability. RESULTS The constructed Chinese DRP classification system comprised six sections [problem（including potential problems）， DRP evaluation， cause （including possible causes of potential problems）， intervention， acceptance of intervention and DRP status]， with 24 primary codes and 96 secondary codes. In the first round of case validation， κ values exceeded 0.4 for all sections except “intervention” and “DRP status”. In the second round， κ values exceeded 0.4 for all sections. In the applicability evaluation of the classification system， positive ratings （“strongly agree” or “agree”） exceeded 85% for all items. Specifically， positive ratings for“the classification system can provide appropriate category selection”，“ the classification system is comprehensive”，“ the classification system is convenient to use” and “the classification system is highly satisfactory” exceeded 92%. CONCLUSIONS The Chinese DRP classification system developed demonstrates both high reliability and applicability， providing an effective and practical classification tool for pharmacists in China to conduct pharmaceutical care.

[摘 要] 目的：探讨m6A调控因子在宫颈癌预后评估、免疫微环境特征及治疗反应中的作用，构建基于m6A调控因子的预后风险模型，并分析其与免疫浸润、药物敏感性及细胞间通信的关系。方法：基于TCGA和GEO数据库中宫颈鳞癌及腺癌（CESC）转录组数据，分析22个m6A调控因子的表达与突变情况；采用LASSO‑Cox回归构建m6A相关预后风险模型，并依据风险评分将患者分为高、低风险组。利用CIBERSORT和ESTIMATE算法评估两组免疫细胞浸润及微环境特征；通过oncoPredict预测抗肿瘤药物敏感性。整合单细胞转录组数据（E-MTAB-12305），采用CellChat分析细胞间通信网络。结果：共鉴定出12个在宫颈癌中差异表达的m6A调控因子。高风险组患者总生存期缩短（P < 0.05），免疫评分降低，且对紫杉醇、氟尿嘧啶、多柔比星等抗肿瘤药物敏感性较差（IC50较高）。单细胞分析显示宫颈癌组织中细胞间通信网络发生改变，其中T细胞与内皮/上皮细胞间的相互作用可能主要由CCL5‑ACKR1和MIF‑（CD74 + CXCR4）配体‑受体介导。在临床样本中，对关键的m6A调控因子进行mRNA和蛋白水平的验证，结果显示部分调控因子在宫颈癌组织中的表达水平高于正常宫颈组织（P < 0.05）。结论：m6A调控因子特征可有效预测宫颈癌患者预后，其风险评分与肿瘤免疫浸润、药物敏感性及细胞通信密切相关，为宫颈癌的预后分层及个体化治疗提供了新的分子依据。

Objective:To investigate the drug resistance gene characteristics, plasmid characteristics and genome tracing of Shigella sonnei causing a bacillary dysentery outbreak in Shandong Province. Methods:Sixty-five Shigella sonnei strains isolated from a 2021 outbreak in a county of Shandong Province were analyzed using antimicrobial susceptibility testing, whole genome sequencing (WGS), characterization of resistance and virulence genes, plasmid profiling, core genome multilocus sequence typing (cgMLST), and single nucleotide polymorphism (SNP) analysis. Results:All isolates had the same resistance phenotype and genotypes and were multidrug-resistant ESBL-producing Shigella sonnei, carrying important virulence genes. Plasmid analysis revealed a conserved genetic arrangement, pil( M/ N/ O2/ P)-tra( F/ H/ J/ K/ N/ O/ P/ Q)-IS Ecp1- blaCTX-M-14-Tn 903- yub( J/ I/ F/ G/ E/ D), and shared across strains from diverse regions and bacterial species. The cgMLST and SNP analyses demonstrated concordant clustering, with all 65 outbreak-related strains forming a single cluster alongside human-derived strains from Guangxi. Conclusion:The ESBL-producing Shigella sonnei responsible for the outbreak shares a homologous relationship with Guangxi human-derived strains, and the detected resistance plasmids and virulence genes underscore the need to strengthen drug resistance surveillance and genome tracing.

[Objective]To discuss the medicinal part and clinical use method of Amomum villosum.[Methods]Through searching the Yaozhi database,the prescriptions containing Amomum villosum were sorted out,and the medicinal part and use method of Amomum villosum were preliminarily understood.Checking the records of the processing specifications of each province and the investigation of the use of Amomum villosum in various medical units across the country with the questionnaire star,in order to understand the actual use of Amomum villosum throughout the country;the prescriptions containing Amomum villosum in Chinese Medicine Hospital of Puyang from June 1 to December 31,2023 were sorted out to indicate the situation of Amomum villosum in the practical application.[Results]There are 1 076 prescriptions containing Amomum villosum in the Yaozhi database.Among them 21 prescriptions clearly mention whether they have shells,5 prescriptions use Amomum villosum shells as medicine;1 prescription mention slightly decocting,and 22 prescriptions have descriptions of crushing.In the processing specifications of 23 provinces and municipalities,13 prescriptions record the use of Amomum villosum,13 prescriptions use Amomum villosum rice(unshelled Amomum villosum),and 5 prescriptions use both Amomum villosum and Amomum villosum rice;questionnaire star collects a total of 38 questionnaires,involving 14 provinces and municipalities,and the usage is basically the same as the processing specifications of each province.In the prescriptions containing Amomum villosum in the second half of 2023 in Chinese Medicine Hospital of Puyang,50.5％of the prescriptions are marked with later decocted,and 49.5％of the prescriptions are decocted together.[Conclusion]Medication site of Amomum villosum:Amomum villosum includes Amomum villosum rice and Amomum villosum shell,but there is no clear conclusion on the medicinal part specific application of which part;Amomum villosum should be crushed before use in the clinic;whether it should be added late during decoction should be determined according to whether its components volatile or non-volatile.

Catechol(CC)is a highly toxic phenolic pollutant,and its sensitive detection holds significant importance for environmental monitoring.Herein,graphene was used as a template to prepare graphdiyne/graphene(GDY/GR)heterogeneous materials,serving as high-performance electrochemical sensing materials for CC determination.GR played the role of an epitaxial template during the growth of GDY.The electrochemical experiment results demonstrated that the glassy carbon electrode(GCE)modified with GDY/GR showed excellent electrochemical response to CC,with a wide linear detection range(1-900 μmol/L)and a low detection limit(0.11 μmol/L).Meanwhile,GDY/GR/GCE also exhibited good anti-interference ability,stability and reproducibility.More importantly,the practicality of GDY/GR/GCE was evaluated and satisfactory results were obtained in actual water samples,which showed significant potential for practical applications in environmental monitoring.

Antibiotics are widely used in clinical treatment of bacterial infection diseases and in the breeding of livestock,poultry and aquatic products.However,the irrational and excessive use of antibiotics not only leads to the emergence of drug-resistant superbugs,but also the antibiotics discharged into the environment pose a significant threat to the environment and human health.Antibiotics have been included in the list of key new pollutants to be controlled.Therefore,the detection of residual antibiotics in environmental media and food is of vital importance for protecting the environment and public health.Among various antibiotic detection methods,electrochemical sensors have attracted extensive attention due to their high sensitivity,low cost,simplicity and rapidity.Appropriate modification of the electrode surface can enhance the sensitivity of electrochemical sensors,reduce interference and expand the detection range.Metal-organic frameworks(MOFs)materials have the advantages of rich types,adjustable structure and activity,high specific surface area and high porosity,and show great application potential in the field of electrochemical sensing.This paper first introduces the synthesis methods of MOFs,reviews the research progress of MOFs-modified electrodes for detection of common antibiotics by electrochemical sensors,and finally looks forward to their future development trends in the field of rapid antibiotic detection.