Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective: To analyze changes in tuberculosis infection among junior high school students before and after tuberculosis exposure, so as to provide a reference for improving school tuberculosis prevention and control measures and policy formulation. Methods: Retrospectively collect data on a tuberculosis outbreak that occurred in a grade of a junior high school in Chongqing in 2025, including tuberculosis screening records of students in this grade upon their enrollment in 2022 (1 156 students) and after two tuberculosis outbreaks in 2023 (206 students) and 2025 (171 students). The Wilcoxon signed rank test for paired design was used to compare the induration diameters of the subjects, and the Chi square test was adopted to analyze the rate of tuberculosis infection among students. Results: In the tuberculosis outbreak in 2023, the rate of tuberculosis infection among close contacts ( 11.84 %) and the rate of tuberculosis infection among freshrman at school enrollment (12.89%) showed no statistically significant difference ( χ 2=0.25, P >0.05). The rate of tuberculosis infection of close contacts in the 2025 tuberculosis outbreak (55.56%) was higher than that in the 2023 outbreak (11.84%) ( χ 2=30.42, P <0.01). Among the 106 students included in the cohort analysis, the median induration diameter was 3.50 (1.50, 7.50) mm in 2023 and 8.75 (4.25, 11.50) mm in 2025, with a statistically significant difference ( Z=-5.76, P <0.01). There was no statistically significant difference between the infection rate in 2022 (16.98%) and that in 2023 (10.38%) ( χ 2=1.96, P =0.16). The infection rate in 2025 (43.40%) was higher than those in 2022 and 2023 ( χ 2=17.55, 29.39, both P <0.017). The seroconversion rate of students in the same class in 2025 ( 58.00 %) was higher than that of students in different classes (16.07%), with a statistically significant difference ( χ 2=20.19, P <0.01). All 72 individuals with latent tuberculosis infections identified during the pandemic in 2023 and 2025 refused to undergo prophylactic treatment. Conclusions The lack of preventive treatment may be the underlying cause of the successive outbreaks during the epidemic. Early detection of infection sources and standardized outbreak management are crucial to controlling the spread of the epidemic.

BackgroundPersistent cognitive impairment is prevalent among patients with stable schizophrenia. While serum total bile acid （TBA） level in acute-phase patients are known to be associated with cognitive dysfunction， the relationship between serum TBA and multi-dimensional cognitive functions in stable phase patients remains unclear. ObjectiveTo investigate the correlation between serum TBA level and cognitive function in patients with stable schizophrenia， and to evaluate its predictive value for cognitive impairment， thereby providing a serological biomarker for the timely identification and objective assessment of cognitive dysfunction. MethodsA cross-sectional study was conducted on 137 inpatients with stable schizophrenia at The Fourth People's Hospital of Yancheng from March to December 2024. All participants met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）. Cognitive function was evaluated using the Chinese Brief Cognitive Test （C-BCT）， patients were categorized into four groups： normal cognition （n=28）， mild impairment （n=28）， moderate impairment （n=47）， and severe impairment （n=34）. Fasting venous blood samples were collected， and serum TBA level was quantified using an enzymatic cycle assay. Spearman correlation analysis was ultilized to determine the relationship between serum TBA level， overall cognitive function， and specific cognitive domains. Binary Logistic regression model was used （adjusting for covariates such as age， gender， and disease duration） to analyze the impact of serum TBA level on overall and individual cognitive functions. The predictive value of serum TBA level for overall cognitive impairment was evaluated using receiver operating characteristic （ROC） curve. ResultsSerum TBA levels differed significantly among the four groups （H=18.677， P<0.01）. Specifically， serum TBA levels in both the moderate and severe cognitive impairment groups were significantly higher than those in the normal cognitive group （adjusted P<0.01）. Serum TBA level was positively correlated with the severity grading of overall cognitive impairment （r_s=0.354， P<0.05）， and negatively correlated with T-scores on the trail making test （r_s=-0.328， P<0.05）， continuous performance test （r_s=-0.247， P<0.05）， digit span （r_s=-0.265， P<0.05）， and symbol coding （r_s=-0.221， P<0.05）. Binary Logistic regression analysis identified serum TBA level as an independent risk factor for overall cognitive impairment （OR=1.322， 95% CI： 1.021 - 1.713， P=0.034）， with a particularly robust predictive ability for impaired information processing speed （OR=1.325， 95% CI： 1.057 - 1.661， P=0.015）. The area under ROC curve （AUC） for serum TBA level in predicting overall cognitive impairment was 0.738， with a sensitivity of 60.61% and a specificity of 78.64%. ConclusionIn patients with stable schizophrenia， elevated serum TBA levels are associated with worse overall cognitive function， as well as deficits in information processing speed， attention， working memory， and executive function. Serum TBA serves as an independent risk factor and exhibits moderate predictive value for overall cognitive impairmen，particularly in the domain of information processing speed. ［Funded by Yancheng Municipal Health Commission Medical Research Project （number， YK2024141）］

Objective:To explore the application effect of phased target teaching combined with case teaching method in neurosurgery intern nurses.Methods:A convenient sampling method was used to select 96 intern nurses in the neurosurgery department of Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2022 to December 2023. The participants were divided into a control group and an observation group. The control group received conventional teaching, while the observation group was given phased target teaching combined with case teaching method based on the control group's curriculum. The clinical work ability, critical thinking ability, teaching performance, teaching satisfaction and cooperation of the intern nurses in both groups were compared.Results:After the intervention, the observation group scored higher in clinical work ability, critical thinking ability, teaching satisfaction and cooperation, teaching performance compared to the control group ( P<0.05) . Conclusions:The application of phased target teaching combined with case teaching method for neurosurgery intern nurses can improve their clinical work ability, critical thinking ability, academic performance, teaching satisfaction and cooperation. This method is worth recommending.

Objective:To evaluate the effect of an opioid-sparing anesthesia strategy primarily using quadratus lumborum block combined with esketamine on early postoperative recovery in patients undergoing laparoscopic radical resection of colon cancer.Methods:This study was a randomized controlled trial. From January 2023 to July 2024, 72 patients of either sex, aged 45-65 yr, with body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective laparoscopic radical resection of colon cancer with general anesthesia at Yichang Central People′s Hospital, were divided into 2 groups ( n=36 each) using a random number table method: control group (group C) and opioid-sparing anesthesia strategy group (group D). Anesthesia was induced with sufentanil and propofol and maintained with propofol and remifentanil in group C. In group D, ultrasound-guided quadratus lumborum block was performed before the start of anesthesia, and anesthesia was induced with esketamine, propofol and lidocaine and maintained with esketamine, propofol, low-dose remifentanil, lidocaine and magnesium sulfate. Patient-controlled intravenous analgesia was carried out at the end of surgery until 48 h postoperatively, using dezocine for rescue analgesia. The Quality of Recovery-15 scores were assessed and recorded at 1 day before operation and 1, 3 and 7 days after operation. Ramsay sedation scores were recorded at 2, 6, 12, 24 and 48 h after surgery. The effective pressing times of patient-controlled analgesia and requirement for rescue analgesia were recorded within 24 h after surgery and during the 24-48 h postoperative period. The intraoperative consumption of opioid, emergence time, duration of postanesthesia care unit stay, time to first flatus, first ambulation time and length of postoperative hospital stay were also recorded. The postoperative complications were recorded during hospital stay and assessed with the Clavien-Dindo classification. Results:Compared with group C, the Quality of Recovery-15 scores were significantly increased at each time point after operation, Ramsay sedation scores were increased at 2, 6 and 12 h after operation, the effective pressing times of patient-controlled analgesia and rate of rescue analgesia were decreased in each postoperative period, the intraoperative consumption of remifentanil was reduced, the time to first flatus, first ambulation time and length of postoperative hospital stay were shortened, the incidence of nausea and vomiting was decreased ( P<0.05), and no significant change was found in the emergence time or duration of postanesthesia care unit stay in group D ( P>0.05). Conclusions:The opioid-sparing anesthesia strategy primarily using quadratus lumborum block combined with esketamine can raise the quality of early postoperative recovery in the patients undergoing laparoscopic radical resection of colon cancer.

Objective:To explore the molecular mechanism of TCM compound Shengxue Tongbian Granules in improving intestinal injury in septic rats through bioinformatics and experimental validation methods.Methods:The GSE131761 gene set was processed by bioinformatics to screen differential genes, then weighted gene co-expression network analysis (WGCNA) was applied to screen modular genes. The intersection of modular genes and differential genes was taken, and finally, the least absolute shrinkage and selection operator (LASSO) technique was applied to further obtain the key targets of sepsis, which was validated by experiments. Totally 72 SD rats were divided into sham-operation group, model group, dexamethasone group (0.15 mg/kg), Shengxue Tongbian Granules low- (0.3 g/kg), medium- (0.6 g/kg), and high-dosage (1.2 g/kg) groups, with 12 rats in each group. Corresponding drug interventions were administered to each treatment group before and 12 hours after modeling. The sham-operation group and the model group were gavaged daily with equal amounts of saline. Samples were collected after 24 hours. HE staining was used to detect the pathological morphology of intestinal tissues in each group of rats; ELISA was used to detect the levels of TNF-α, diamine oxidase (DAO), IL-6, IL-10, and myeloperoxidase (MPO) in rat serum. Immunohistochemistry was used to detect the protein expressions of MPO and neutrophil elastase (NE/LANE) in intestinal tissue, and Western blot was used to detect the protein expression of peptidyl arginine deaminase (PAD4) in intestinal tissue.Results:Seven final key genes related to sepsis were selected, namely ANXA3, CYP1B1, FCAR, LILRA5, PADI4, NOV, and S100A12. Experimental results showed that drug administration alleviated intestinal injury; compared with the model group, the levels of TNF-α, IL-6, MPO, and DAO decreased in the Shengxue Tongbian Granules high-dosage group ( P<0.05), the levels of ELANE and MPO were reduced in Shengxue Tongbian Granules low-, medium-, and high-dosage groups ( P<0.05), and PAD4 expression was reduced in the Shengxue Tongbian Granules high-dosage group ( P<0.05). Conclusion:Shengxue Tongbian Granules can improve the intestinal injury of septic rats, and the mechanism may be related to the inhibition of PAD4-mediated formation of NETs and the improvement of inflammatory response.

Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

Objective To quantify the lower limb coordination and coordination variability of children with spastic cerebral palsy(CP)during flat ground walking using vector coding technology.Methods From September to December,2023,eight children with spastic CP(patients)from Ji'nan Rehabilitation Hospi-tal and Ji'nan Special Education School,and eight healthy children(controls)from communities walked on a treadmill at a speed of 0.45 m/s.Lower limb kinematic data were collected using Vicon,a three-dimensional mo-tion capture system.Vector coding technology was used to quantify the temporal and spatial parameters of ipsilat-eral lower limb joints to calculate joint coupling angles and coupling angle variability(CAV).Results In the first and second double support phase,the hip-knee coupling angle was significantly larger in the patients than in the controls(|t|>2.317,P<0.05).In the swing phase,the hip-ankle and knee-ankle coupling angles were significantly larger in the patients(|t|>2.346,P<0.05).In the first double support phase and the single support phase,CAV of the hip-knee and hip-ankle were significantly larger in the patients(|t|>2.454,P<0.05),and they were smaller in the swing phase(t>2.560,P<0.05).In the second double support phase and the swing phase,CAV of the knee-ankle was significantly larger in the patients(|t|>2.909,P<0.05).Conclusion Coordination among hip,knee and ankle joints is poor for children with spastic CP during both the stance and swing phases of walking,and variability is more during the stance phase.

Objective To explore the diagnostic value of dual-low-dose CT energy spectral imaging combined with adaptive statis-tical iterative reconstruction-Veo(ASIR-V)in distinguishing benign and malignant thyroid nodules.Methods A total of 242 patients with thyroid nodules were included.In part Ⅰ,the initial 90 patients were randomly and equally assigned to the conventional scan group,the low radiation dose group,and the dual-low-dose group.Both subjective and objective image qualities,the radiation dose,and contrast agent dosage in these three groups were evaluated,respectively.In part Ⅱ,the remaining 152 patients underwent dual-low-dose CT energy spectral scanning.Radiographic features of thyroid nodules in benign and malinant groups were observed,fol-lowed by spectral imaging analysis.The iodine concentration(IC)value,normalized iodine concentration(NIC)value,effective atomic number(Eff-Z),and λHU value of benign and malignant nodules were measured and compared,respectively.Results There were significant differences in nodule morphology,sign of edge truncation,enhancement characteristics and nodule boundary enhancement between benign and malignant thyroid nodules(P<0.05).There were statistically significant differences in IC value,NIC value,and λHU value in the venous phase among the three groups(P<0.05).The sensitivity and specificity of IC,NIC,λHU were 81.6%and 60.0%,86.4%and 67.5%,88.8%and 65.0%,respectively.The area under the curve(AUC)of combining the three energy spectral parameters with radiographic fea-tures via binary logistic regression model was 0.905,and the sensitivity and specificity were 82.4%and 87.5%,respectively.The effective dose(ED)in the dual-low-dose group was reduced by 60.13%com-pared to the conventional scan group,and the contrast agent dos-age was reduced by 38.56%.Conclusion The dual-low-dose CT energy spectral imaging combined with ASIR-V significantly reduced the radiation dose and the contrast agent dosage,and might help in distinguishing between benign and malignant thyroid nodules,demonstrating considerable clinical application value.