OBJECTIVE To investigate the efficacy and safety of Wuling capsules combined with fluoxetine in the treatment of adolescents with first-episode moderate-to-severe depressive disorder accompanied by insomnia. METHODS The clinical data of 476 adolescents with first-episode moderate-to-severe depression accompanied by insomnia admitted to our hospital from June 2022 to May 2025， were retrospectively collected. According to the initial treatment regimen， patients were divided into a control group （241 cases， treated with fluoxetine alone） and an observation group （235 cases， treated with Wuling capsules combined with fluoxetine）. The depression severity （Hamilton Depression Rating Scale-17 Item and the Self-Rating Depression Scale scores）， sleep quality （Pittsburgh Sleep Quality Index score， sleep latency， wake after sleep onset， total sleep time， sleep efficiency）， serum neuroendocrine indicator （cortisol） and inflammatory markers （C-reactive protein， interleukin-6） were compared between the two groups before treatment and at 4th and 8th weeks of treatment. The effective rate at 8th weeks and the occurrence of adverse drug reactions （ADRs） were also compared between the two groups. RESULTS Before treatment， there were no significant differences in depression severity， sleep quality， serum neuroendocrine indicator， and inflammatory markers between the two groups （ P ＞0.05）. At 4th and 8th weeks， both groups showed significant improvement in these indicators compared to those before treatment， with the observation group demonstrating significantly greater improvement than the control group at the corresponding time points （ P ＜0.05）. At 8th week， the eff ective rate of the observation group was 90.21%， significantly higher than 80.50% in the control group （ P ＜0.05）. The incidence of nausea， headache， fatigue， dry mouth， and palpitations， as well as the total incidence of ADRs， did not differ significantly between the two groups （ P ＞0.05）. CONCLUSIONS Wuling capsules combined with fluoxetine can significantly improve the effective rate in adolescents with first-episode moderate-to-severe depression accompanied by insomnia， accelerate the relief of depressive symptoms， improve sleep quality， and reduce serum neuroendocrine indicator and inflammatory markers， with a favorable safety profile.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

In recent years,the incidence and mortality of heatstroke have been increasing annually alongside global warming,with a marked rise in cases exhibiting atypical symptoms.To address the increasingly complex challenges in heatstroke prevention and treatment,Heatstroke Prevention and Treatment Research Center of Chinese PLA,Expert Group of Heatstroke Prevention and Treatment of Chinese PLA,and Chinese PLA Professional Committee of Critical Care Medicine have jointly developed this guideline(2025 edition).Utilizing the Grading of Recommendations Assessment,Development and Evaluation(GRADE)system,Appraisal of Guidelines for Research and Evaluation(AGREE)criteria,and Reporting Items for Practice Guidelines in Healthcare(RIGHT)standards,and based on the 2015 draft"Expert Consensus on the Standardized Diagnosis and Treatment of Heatstroke"and the 2019"Chinese Expert Consensus on the Diagnosis and Treatment of Heatstroke",this guideline has been crafted.This guideline provides 25 evidence-based recommendations to guide the prevention,treatment and research of heatstroke,which thoroughly covers 8 critical domains:clinical classification,pathophysiological mechanisms,clinical manifestations,diagnostic criteria,differential diagnosis,treatment protocols,rehabilitation and return to work,and prevention.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

This study investigated the drug resistance and genetic relationships among strains co-existing in animals,the environ-ment,and the living quarters of employees at large-scale pig farms in certain regions of Shandong Province,to provide a scientific ba-sis for elucidating the transmission mechanisms of drug-resistant bacteria through bacterial traceability analysis.Samples were col-lected from two pig farms,and bacteria were isolated and purified.The species of the isolated strains were identified via 16S rRNA gene sequencing.Antimicrobial susceptibility testing was conducted with a VITEK-2 Compact system and the disk diffusion method for strains present in pigs,the environment,and living areas.Furthermore,whole-genome sequencing was performed on the Illumina Miniseq platform to annotate drug resistance genes,and multilocus sequence typing(MLST)and core genome single nucleotide poly-morphism(cgSNP)analyses were used to trace the resistant strains.Three species—Staphylococcus aureus,Pseudomonas aeruginosa,and Bacillus cereus—were isolated and cultured from animals,the environment,and employee living areas,and their distributions were analyzed.These strains exhibited diverse drug resistance spectra and genetic diversity.Additionally,the strains displayed highly consistent resistance profiles,resistance genes,ST types,and SNP loci in pig urine,soil both inside and outside the facility,human drinking water,and the cafeteria and dormitories.Our findings indicated a potential risk of transmission of opportunistic pathogens be-tween the pig farming area and the living quarters.Particular attention should be paid to the environmental transmission of methicillin-resistant Staphylococcus aureus.

Objective:To investigate the effect of hydrogen on the expressions of stromal interaction molecule 1 (STIM1) and Ca 2+-release-activated-Ca 2+ channel protein 1 (Orai1) and the protective effect of hydrogen on septic mice acute lung injury (ALI). Methods:Forty-eight male ICR mice were divided into sham operation group (Sham group), hydrogen control group (Sham+H 2 group), sepsis group (SS group) and hydrogen intervention group (SS+H 2 group) according to a random number table method, with 12 mice in each group. Sepsis mice model were established by cecal ligation and puncture (CLP). Sham group and Sham+H 2 group did not undergo CLP, other operations were the same as follow. Sham+H 2 group and SS+H 2 group received 1 hour inhalation of 2% H 2 at 1 hour and 6 hours after CLP or sham operation. At 24 hours after CLP, 6 mice in each group were sacrificed for observing pulmonary microvascular permeability after injecting Evans blue (EB) through tail vein. Other 6 mice in each group were sacrificed for obtaining fresh lung tissue to observe the lung pathological change and lung wet/dry (W/D) weight ratio. The protein expressions and distribution of STIM1 and Orai1 in lung tissue were detected by Western blotting and immunofluorescence staining. The mRNA expressions of STIM1 and Orai1 in lung tissue were detected by reverse transcriotion-polymerase chain reaction (RT-PCR). Coimmunoprecipitation was used to observe STIM1-Orai1 interaction. Finally, pulmonary microvascular endothelial cells (PMVEC) of mice were cultured in vitro and randomly divided into four groups for inoculation onto culture plates: Control group, rich hydrogen solution group (Control+H 2 group), lipopolysaccharide (LPS) group and rich hydrogen solution intervention group (LPS+H 2 group). PMVECs in Control group and LPS group were cultured in normal medium. Control+H 2 group and LPS+H 2 group were cultured in saturated hydrogen medium. LPS group and LPS+H 2 group were added with LPS at 5 μg/mL. Intracellular Ca 2+ ([Ca 2+]i) concentration of PMVECs were detected by Fluo-4/AM green dye. Results:Compared with Sham group, the pathological score and lung W/D ratio were significantly increased in SS group at 24 hours after CLP (pathological score: 11.00±1.41 vs. 1.00±0.63, lung W/D ratio: 7.63±0.52 vs. 3.45±0.58, both P < 0.05), the content of EB in the lung tissue was increased (μg/g: 0.16±0.02 vs. 0.09±0.02, P < 0.05). Compared with SS group, the pathological score and lung W/D ratio were decreased in SS+H 2 group (pathological score: 3.50±1.05 vs. 11.00±1.41, lung W/D ratio: 4.45±0.45 vs. 7.63±0.52, both P < 0.05), the content of EB in the lung tissue was decreased (μg/g: 0.13±0.02 vs. 0.16±0.02, P < 0.05), which prove that hydrogen can improve ALI caused by sepsis. Compared with Sham group, the protein and mRNA expressions of STIM1 and Orai1 were up-regulated in SS group (relative expression level of STIM1 protein: 3.08±0.32 vs. 1.00±0.00, relative expression level of STIM1 mRNA: 3.65±0.24 vs. 1.00±0.00, relative expression level of Orai1 protein: 3.63±0.23 vs. 1.00±0.00, relative expression level of Orai1 mRNA: 3.80±0.22 vs. 1.00±0.00, all P < 0.05), while the protein and mRNA expressions of STIM1 and Orai1 were down-regulated in SS+H 2 group compared with SS group (relative expression level of STIM1 protein: 1.78±0.13 vs. 3.08±0.32, relative expression level of STIM1 mRNA: 1.76±0.28 vs. 3.65±0.24, relative expression level of Orai1 protein: 1.92±0.22 vs. 3.63±0.23, relative expression level of Orai1 mRNA: 1.85±0.18 vs. 3.80±0.22, all P < 0.05). Coimmunoprecipitation staining results showed that there was no statistically significance in the association between STIM1 and Orai1 in Sham group and Sham+H 2 group. Compared with Sham group, the STIM1-Orai1 interaction was increased in SS group (relative expression level: 3.71±0.37 vs. 1.00±0.00, P < 0.05), while the STIM1-Orai1 interaction was decreased in SS+H 2 group compared with SS group (relative expression level: 2.17±0.29 vs. 3.71±0.37, P < 0.05). There were no statistically significant differences in various indicators between Sham group and Sham+H 2 group. In vitro, the intracellular [Ca 2+]i concentration in PMVECs was increased in LPS group compared with Control group using Fluo-4/AM green dye. The intracellular [Ca 2+]i concentration in PMVECs was decreased in LPS+H 2 group compared with LPS group. Conclusion:The protective effect of hydrogen on lung tissues in septic mice is related to the inhibition of STIM1, Orai1 and the interaction between them.

Attention is the cornerstone of effective functioning in a complex and information-rich world. While the neural activity of attention has been extensively studied in the cortex, the brain-wide neural activity patterns are largely unknown. In this study, we conducted a comprehensive analysis of neural activity across the mouse brain during attentional processing using EEG and c-Fos staining, utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the c-Fos activation patterns. Our findings reveal that a wide range of brain regions are activated, notably in the high-order cortex, thalamus, and brain stem regions involved in advanced cognition and arousal regulation, with the central lateral nucleus of the thalamus as a strong hub, suggesting the crucial role of the thalamus in attention control. These results provide valuable insights into the neural network mechanisms underlying attention, offering a foundation for formulating functional hypotheses and conducting circuit-level testing.
Animals ; Attention/physiology* ; Mice ; Brain/physiology* ; Male ; Electroencephalography ; Reaction Time/physiology* ; Brain Mapping ; Mice, Inbred C57BL ; Choice Behavior/physiology* ; Proto-Oncogene Proteins c-fos/metabolism*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant