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 evaluate the effect of Bu-Zhong-Yi-Qi-Tang (BZYQT) combined with low molecular weight heparin (LMWH) on lower limb deep vein thrombosis (DVT) after fracture fixation in aged rabbits.Methods:Thirty-two elderly New Zealand rabbits of either sex, aged 36 months, weighing 3.5-4.0 kg, were divided into 4 groups ( n=8 each) using the random number table method: control group (C group), fracture fixation group (F group), low molecular weight heparin group (L group) and BZYQT combined with LMWH group (BL group). A model of fixation surgery for right femoral shaft fracture was established in anesthetized rabbits in F, L and BL groups. Starting from postoperative day 1, BL group received BZYQT at 3.6 ml/kg via gavage, F and L groups received normal saline at 3.6 ml/kg via gavage, L and BL groups received subcutaneous injection of LMWH at 200 IU/kg, and all the administrations were performed daily at 08: 00 for 7 consecutive days. On postoperative day 7, ultrasound examination was performed to assess lower limb DVT. Blood samples were collected from the marginal ear vein for determination of the serum concentrations of cortisol (COR), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and endothelin-1 (ET-1) by enzyme-linked immunosorbent assay. Femoral vein specimens were obtained under anesthesia for microscopic examination of the pathological changes of the femoral vein lumen and endothelial tissues (by HE staining) and of the morphology of vascular endothelial cells (by the transmission electron microscopy). Results:Compared with C group, the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly increased in F, L and BL groups, and the incidence of lower limb DVT within 7 days after surgery was significantly increased in F and L groups ( P<0.05). Compared with F group, the incidence of lower limb DVT within 7 days after surgery was significantly decreased in L and BL groups, and the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly decreased ( P<0.05), and the pathological damage was significantly reduced in BL group. Compared with L group, the incidence of lower limb DVT and concentration of IL-6 were significantly decreased ( P<0.05), and pathological damage was significantly alleviated in BL group. Conclusions:BZYQT combined with LMWH can prevent the occurrence of lower limb DVT after fracture fixation in aged rabbits.

Objective:To understand the occurrence of different patterns of multimorbidity among children and adolescents aged 9-18 in Tianjin City and analyze the cumulative effects of lifestyle on these patterns of multimorbidity.Methods:From September to November 2022, a stratified cluster random sampling method was used to select students from primary schools, junior high schools, general high schools, and vocational schools in 16 districts of Tianjin to screen for height, weight, blood pressure, distant vision, and diopter. One year later, a follow-up measurement and questionnaire survey were conducted. The log-binomial model was used to analyze the strength of the association between lifestyle factors and different patterns of multimorbidity.Results:The age of 9 488 students was (12.37±2.49) years old, including 4 999 boys and 4 489 girls. The detection rates of three patterns of multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia were 6.63%, 9.32%, and 4.21%, respectively. The detection rates of the three types of multimorbidity in boys were higher than those in girls (all P<0.001). The detection rate of overweight obesity and high blood pressure in suburban areas was higher than that in urban areas ( P=0.002). The detection rate of overweight obesity and myopia in suburban areas was lower than that in urban areas ( P=0.034). The detection rate of overweight obesity and myopia among those aged 9-12 years old was higher than other age groups (all P<0.001). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity and high blood pressure was 0.79 (0.68-0.92). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity with high blood pressure and myopia was 0.82 (0.67-0.99). Compared with children and adolescents with 0-2 favorable lifestyle factors, those with 4-5 favorable lifestyle factors had a lower risk of overweight obesity and high blood pressure ( ARR=0.84, 95% CI: 0.59-0.92). Conclusion:Boys aged 9-18 in Tianjin City are more prone to multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia. Children and adolescents with 4-5 favorable lifestyle factors have a reduced risk of occurrence of overweight obesity and high blood pressure. Lifestyle has cumulative effects on multimorbidity of overweight obesity and high blood pressure.

Objective This study aimed to explore the clinical and etiological characteristics of bloodstream infections in diabetic patients with different levels of glycosylated hemoglobin(HbA1c)for improving empirical diagnosis and treatment in clinical practice.Methods A retrospective study was conducted for diabetic patients with bloodstream infections who were admitted to Sichuan Mental Health Center from 2017 to 2023.Patients were assigned to one of the three groups based on HbA1c levels:low level(HbA1c＜7.0％),medium level(7.0％≤HbA1c＜9.0％),high level(HbA1c≥9.0％).The clinical data,pathogen distribution,and antimicrobial resistance were analyzed and compared between groups.Results A total of 426 diabetic patients with bloodstream infection were included.The proportion of community-acquired bloodstream infection,acidosis,and liver abscess in the high level HbA1c group were significantly higher than those in the medium and low level HbA1c groups.Overall,452 strains of nonduplicate pathogenic bacteria were isolated,the most common of which were Escherichia coli(47.1％),Klebsiella pneumoniae(23.0％),and Staphylococcus aureus(5.8％).The pathogens of bloodstream infections varied with different HbA1c levels.The proportion of K.pneumoniae in the high-level HbA1c group(30.7％)was significantly higher than that in the low-level HbA1c group(15.1％)and medium level HbA1c group(16.0％).More than 50％of E.coli isolates were resistant to piperacillin,cefazolin,and ampicillin,while lower than 10％of the isolates were resistant to cefoxitin and minocycline,and lower than 1％of the isolates were resistant to piperacillin-tazobactam,meropenem,imipenem,and amikacin.The E.coli strains isolated from hospital-acquired infections showed slightly higher resistance rates to penicillin,cephalosporins,aminoglycosides,and fluoroquinolones than the strains isolated from community-acquired infections.K.pneumoniae strains showed low resistance rates(＜30％)to the commonly used antibiotics.However,the strains isolated from hospital-acquired infections were significantly more resistant to cephalosporins,carbapenems,and aminoglycosides than the strains isolated from community-acquired infections.Conclusions E.coli,K.pneumoniae and S.aureus were the common pathogens of bloodstream infections in diabetic patients.Poor HbA1c control was associated with K.pneumoniae bloodstream infection,especially those originated from liver abscess.The antibiotic-resistant E.coli and K.pneumoniae strains were prevalent in hospital-acquired bloodstream infections in diabetic patients.Antimicrobial resistance surveillance should be strengthened for this patient population.

Diabetes is one of the major chronic non-communicable diseases in China. This article discusses the progress of diabetes prevention and control under the leadership of the government and how to integrate the National Diabetes Prevention and Control Center (DPCC) into the work of primary medical and health institutions in Yunnan Province, providing reference and experience for diabetes prevention and control efforts in the central and western regions of China.

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.