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 explore the echocardiographic features of critically ill patients with infection, and to evaluate the predictive value of echocardiographic parameters for 28-day mortality and myocardial injury. Methods Using a single-center prospective cohort design, 120 critically ill patients with infection admitted to the Intensive Care Unit, Jinshan Hospital of Fudan University from January 2024 to January 2025 were enrolled consecutively. According to the severity of infection, patients were divided into the sepsis group (n＝75) and the non-sepsis group (n＝45). Cox proportional hazards models and modified Poisson regression were used to analyze risk factors of 28-day all-cause mortality and myocardial injury. Kaplan-Meier survival curve and log-rank test were used to assess prognosis differences among patients with different ultrasound parameters. ROC curve and area under the curve (AUC) were applied to evaluate the predictive performance of ultrasound parameters, and restricted cubic spline (RCS) model was used to explore nonlinear relationships. Results The E/e′ ratio was significantly higher in the sepsis group than in the non-sepsis group (P＜0.001), while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the sepsis group (P＜0.05). The Cox proportional hazards model found no association between ultrasound parameters and 28-day all-cause mortality. Modified Poisson regression showed that, after adjusting for confounding factors, elevated E/e′ was an independent risk factor of myocardial injury (RR＝1.12, 95% CI 1.07–1.17, P＜0.001). Survival analysis demonstrated that patients with E/e′ ＞10.9 had lower 28-day survival rates (P＝0.02), and the AUC for E/e′ predicting myocardial injury was 0.835. RCS analysis suggested a nonlinear relationship between E/e′ and myocardial injury risk (P＜0.001). Conclusions E/e′, LVEF, and LVFS have no significant predictive value for 28-day mortality risk in critically ill patients with infections. Elevated E/e′ is an independent risk factor of myocardial injury in such patients, with a nonlinear relationship.

Objective: To explore the relationship between socio ecological risk factors (SERF), physical activity (PA) developmental trajectories, and depressive symptoms among junior and senior high school students in Tianjin, in order to provide theoretical support for comprehensive interventions for adolescent depression. Methods: A longitudinal follow up design was adopted. In September 2022, a baseline survey was conducted using a stratified cluster random sampling method in two junior high schools and two senior high schools in Tianjin, collecting data on students basic information, SERF, PA, and depressive symptoms. Two follow up surveys were conducted in September 2023 and 2024, yielding 588 valid participants. Latent class growth analysis (LCGA) was used to identify PA developmental trajectory categories among junior and senior high school students. Logistic regression was applied to examine the associations between depressive symptoms and SERF as well as PA trajectories. Results: The detection rates of depressive symptoms among Tianjin junior and senior high school students over the three years were 26.53%, 20.24%, and 21.26 %, respectively. Depressive symptoms were positively correlated with SERF ( OR=1.04, 95%CI=1.03-1.05, P <0.05). The highest risks were observed in the individual dimension and family dimension ( OR =1.28, 1.21, both P <0.05). LCGA identified three PA trajectory groups:persistently low level (80.65%), persistently high level (4.58%), and slowly increasing group ( 14.77 %). Multivariate regression analysis showed that compared with the persistently low level PA, the slowly increasing PA significantly reduced the risk of depressive symptoms ( OR=0.44, 95%CI =0.20-0.88), while SERF still increased the risk of depressive symptoms ( OR=1.04, 95%CI =1.03-1.05) (both P <0.05). Conclusion SERF are risk factors for depression symptoms among junior and senior high school students, whereas slowly increasing PA development trajectory demonstrates a protective effect.

Patients with inflammatory bowel disease (IBD) require long-term pharmacotherapy. Due to the wide variety of clinically available drugs, medication safety has become increasingly concerning. As an indispensable component of pharmaceutical formulations, drug excipients may induce various adverse reactions, including rash, allergic responses, and gastrointestinal discomfort, and may even lead to severe organic injury. However, they are often overlooked in clinical practice. Therefore, identifying and managing excipient-related adverse reactions is crucial for ensuring medication safety. To address this issue, this article systematically reviews common excipients in IBD therapeutics, the underlying mechanisms of excipient-induced adverse reactions, and corresponding management strategies, aiming to enhance clinicians' awareness of excipient-related issues, improve their ability to recognize and manage such reactions, and ultimately ensure patient safety.

Objective: To explore the value of body measurement indicators in screening for metabolic syndrome (MS), so as to provide the basis for early detection and prevention of MS. Methods: The individuals who were 18 years old or above and underwent physical examinations at a tertiary hospital of Xinjiang Uygur Autonomous Region were selected using the convenience sampling method. Demographic information, lifestyle, waist circumference (WC) and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. The associations of WC, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body roundness index (BRI), abdominal volume index (AVI), lipid accumulation product (LAP) and visceral adiposity index (VAI) with MS were analyzed using a multivariable logistic regression model. The screening values of these body measurement indicators for MS were assessed by receiver operating characteristic (ROC) curves. Results: A total of 37 921 individuals were recruited, including 20 666 males (54.50%) and 17 255 females (45.50%), and had a median age of 41.00 (interquartile range, 20.00) years. There were 7 988 cases of MS, with a detection rate of 21.06%. Multivariable logistic regression analysis showed that WC, WHR, LAP and VAI were statistically associated with MS (all P<0.05), and the risk of MS increased with the levels of these indicators (all Ptrend<0.05), after adjusting for confounding factors (gender, age, lifestyle, etc.). The area under the ROC curve (AUC) of LAP for screening MS was the highest among single indicators, at 0.930 (95%CI: 0.927-0.933), and the optimal cut-off value was 43.13, Youden's index was 0.720, the sensitivity was 88.01%, and the specificity was 84.04%. The combined indicators of WC×VAI for screening MS had the highest AUC, which was 0.937 (95%CI: 0.935-0.939), and the optimal cut-off value was 0.17, Youden's index was 0.730, the sensitivity was 91.88%, and the specificity was 81.07%. The DeLong test showed that the AUC of WC×VAI for screening MS was higher than that of WC, WHR, LAP and VAI, respectively (all P<0.05). Conclusion The value of combining WC and VAI for screening MS is higher than other body measurement indicators.

ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 （GPX4）-acyl-CoA synthetase long-chain family member 4 （ACSL4） axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury （SCI）. MethodsNinety rats were randomly divided into five groups： sham operation group， model group， low-dose Buyang Huanwutang group （12.5 g·kg^-1）， high-dose Buyang Huanwutang group （25 g·kg^-1）， and Buyang Huanwutang + inhibitor group （25 g·kg^-1 + 5 g·kg^-1 RSL3）. The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan （BBB） scale. Hematoxylin-eosin （HE）， Nissl， and Luxol fast blue （LFB） staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein （MBP）， GPX4， and ACSL4. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay （ELISA） was performed to measure the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD）. Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group， the model group exhibited significantly reduced BBB scores （P<0.01）， severe pathological damage in spinal cord tissue， and marked mitochondrial ultrastructural disruption. In addition， the model group showed a decrease in the number of NeuN-positive cells （P<0.01）， reduced fluorescence intensity of MBP and GPX4 （P<0.01）， lower levels of GSH and SOD （P<0.01）， and downregulated mRNA expression of GPX4 （P<0.01）. Moreover， compared to the sham operation group， the model group had elevated levels of ROS， MDA， and tissue iron content （P<0.01）， along with increased fluorescence intensity and mRNA expression of ACSL4 （P<0.01）. Compared with the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group showed significantly improved BBB scores （P<0.05， P<0.01） and exhibited less severe spinal cord tissue damage， reduced edema and inflammatory cell infiltration， increased neuronal survival， and more intact myelin structures. Additionally， mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP （P<0.05， P<0.01）. Furthermore， Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 （P<0.01） and decreased the fluorescence intensity and mRNA expression of ACSL4 （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. Finally， the Buyang Huanwutang group significantly decreased ROS， MDA， and tissue iron content （P<0.01） and significantly increased GSH and SOD levels （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis， reduces secondary neuronal and myelin injury and oxidative stress， and ultimately promotes the recovery of neurological function.

OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

Objective:To learn about the current status of fluoride in drinking water from historical drinking water-borne endemic fluorosis areas in Tianjin, and to evaluate the non-carcinogenic health risk of fluoride in drinking water for children.Methods:A cross-sectional survey was conducted from January to November 2023 to investigate the fluoride level in drinking water in 2 028 villages with children aged 6 - < 18 years residing in 10 historical drinking water-borne endemic fluorosis areas in Tianjin. Based on the risk assessment model of the Technical Guide for Environmental Health Risk Assessment of Chemical Exposure (WS/T 777-2021) and the child specific exposure parameters in the highlights of the Chinese exposure factors handbook (Children volume), the hazard index (HI) was used to quantify and assess the non-carcinogenic health risk of fluoride in drinking water for children of different age groups (6 - < 9, 9 - < 12, 12 - < 15, 15 - < 18 years old).Results:The water fluoride level [ M ( Q1, Q3)] in the historical drinking water-borne endemic fluorosis areas in Tianjin was 0.28 (0.12, 0.85) mg/L, ranging from 0.05 to 1.08 mg/L. The HI values of children in each age group were 0.218, 0.185, 0.136, and 0.124, respectively, all < 1, indicating low non-carcinogenic health risk. Among them, the age group of 6 - < 9 years old had the highest HI value, with HI values ranging from 0.148 to 0.412 in 10 regions, and the difference was statistically significant ( H = 594.62, P < 0.001). Comparing drinking water of different source types, regions, and treatment methods, there were statistically significant differences in HI values among children of different age groups ( Z = - 9.25, - 9.25, - 9.25, - 9.25, - 6.96, - 6.96, - 6.96, - 6.96, H = 146.75, 146.75, 146.75, 146.75, P < 0.001). Conclusion:The non-carcinogenic health risks of fluoride in drinking water for children in historical drinking water-borne endemic fluorosis areas of Tianjin are relatively low, but there is still a need to strengthen monitoring and early warning for young children.

Objective:To learn about the iodine nutrition status of pregnant women in Tianjin and analyze the influencing factors of moderate to severe iodine deficiency in pregnant women.Methods:From January 2022 to December 2024, a stratified random sampling method was adopted. Each year, five sampling areas were divided into the east, west, south, north and central directions in 16 districts of Tianjin. Ten pregnant women from one township/street in each area were selected for questionnaire surveys. Household salt samples and random urine samples were collected to measure salt iodine and urinary iodine levels. Multivariate logistic regression was used to analyze the influencing factors of moderate to severe iodine deficiency in pregnant women, and a restricted cubic spline model was used to analyze the dose-response relationship between the risk of moderate to severe iodine deficiency in pregnant women and salt iodine level.Results:A total of 2 532 pregnant women in Tianjin were surveyed, with an age of (30.70 ± 4.44) years. Among them, 53.20% (1 347/2 532) had received health education, and 52.45% (1 328/2 532) actively supplemented iodine. A total of 2 532 household salt samples of pregnant women were tested, with a median salt iodine level of 23.66 mg/kg. The coverage rate of iodized salt was 74.45% (1 885/2 532), the qualified rate of iodized salt was 87.59% (1 651/1 885), and the consumption rate of qualified iodized salt was 65.21% (1 651/2 532). A total of 2 532 urine samples of pregnant women were tested, with a median urinary iodine level of 151.68 μg/L. Among them, 652, 1 348 and 532 urine samples were collected from pregnant women in the early, middle, and late stages of pregnancy, respectively, with median urinary iodine levels of 150.80, 153.00 and 143.68 μg/L, respectively. Multivariate logistic regression analysis showed that consuming iodized salt was a protective factor for the moderate to severe iodine deficiency in pregnant women ( OR = 0.70, 95% CI: 0.58 - 0.86, P < 0.001). Restricted cubic spline analysis showed that there was a linear dose-response relationship between the risk of moderate to severe iodine deficiency in pregnant women and salt iodine level ( Poverall < 0.001, Pnonlinear = 0.065). Further stratified analysis revealed that there was a linear dose-response relationship between the risk of moderate to severe iodine deficiency in pregnant women who had received iodine supplementation and salt iodine level ( Poverall = 0.018, Pnonlinear = 0.554), while there was a nonlinear dose-response relationship between the risk of moderate to severe iodine deficiency in pregnant women who had not received iodine supplementation and salt iodine level ( Poverall < 0.001, Pnonlinear = 0.029). Conclusions:From 2022 to 2024, the overall iodine level of pregnant women in Tianjin is appropriate, but some pregnant women are at risk of iodine deficiency. Consuming iodized salt is a protective factor against the moderate to severe iodine deficiency in pregnant women. It is still necessary to further implement comprehensive prevention and control measures mainly based on iodized salt.

Objective:To investigate the prevalence of dental fluorosis in children in Tianjin and study its influencing factors.Methods:From January to December 2023, 5 affected villages were selected from each of the drinking water-borne endemic fluorosis (drinking water-borne fluorosis for short) areas of 10 agricultural areas in Tianjin, and 50 children aged 8 - 12 years (gender and age balanced) were selected from each affected village for questionnaire survey and dental fluorosis examination. At the same time, water samples from affected villages and children's one random urine sample were collected to test for fluoride levels in water and urine. Multivariate logistic regression was used to analyze the influencing factors of dental fluorosis prevalence in children, and a restricted cubic spline model was used to analyze the dose-response relationship between the years of water improvement and dental fluorosis prevalence.Results:A total of 50 water samples were collected, with water fluoride levels ranging from 0.05 to 0.85 mg/L. All affected villages had completed the water improvement and the water fluoride levels were qualified. A total of 2 439 urine samples were collected from children, with urinary fluoride levels ranging from 0.05 to 12.56 mg/L and a geometric mean of 0.82 mg/L. A total of 2 439 children were examined for dental fluorosis, with a detection rate of 22.67% (553/2 439). The results of multivariate logistic regression analysis showed that age ( OR = 1.26, 95% CI: 1.15 - 1.37, P < 0.001), father's education level of junior high school or below ( OR = 1.57, 95% CI: 1.04 - 2.38, P = 0.033), and high urinary fluoride (0.74 - 1.58 mg/L: OR = 1.59, 95% CI: 1.19 - 2.13, P = 0.002; 1.59 - 12.56 mg/L: OR = 2.00, 95% CI: 1.48 - 2.70, P < 0.001) were risk factors for dental fluorosis prevalence in children. The total annual household income with 40 000 to 80 000 yuan ( OR = 0.76, 95% CI: 0.58 - 0.99, P = 0.041), father's occupation was self-employed and other occupation ( OR = 0.69, 95% CI: 0.51 - 0.92, P = 0.013), the years of water improvement in affected villages ≥10 years ( OR = 0.39, 95% CI: 0.30 - 0.50, P < 0.001), and the material of the drinking water container at home was stainless steel products ( OR = 0.58, 95% CI: 0.40 - 0.85, P = 0.005), ceramic or glass products ( OR = 0.66, 95% CI: 0.48 - 0.90, P = 0.010) were protective factors for dental fluorosis prevalence in children. By constructing a restricted cubic spline model, it was found that there was a linear dose-response relationship between the prevalence of dental fluorosis in children and the years of water improvement in affected villages ( Poverall < 0.001, Pnonlinear = 0.059). The longer the years of water improvement, the lower the risk of dental fluorosis prevalence. Conclusions:The detection rate of dental fluorosis in children in Tianjin is relatively high. The fluoride reduction and water improvement measures implemented in drinking water-borne fluorosis areas can effectively reduce the risk of dental fluorosis prevalence. Factors such as age, urinary fluoride, economic conditions, and lifestyle also have important impacts on the prevalence of dental fluorosis.