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 value of lumbar volumetric bone mineral density (vBMD) measured by quantitative computed tomography (QCT) in predicting coronary artery calcification (CAC).Methods:This retrospective, cross-sectional study included a total of 991 patients (504 male and 487 female) who underwent coronary artery CT angiography (CTA) and chest, abdomen, or lumbar spine CT examinations at Taihe County People′s Hospital from January 2023 to June 2024. Lumbar vBMD was measured by QCT. The coronary artery calcification score (CACS) was calculated using an artificial intelligence-assisted diagnostic system. Patients were categorized into a low calcification group (CACS≤100, 592 cases) and a moderate-to-severe calcification group (CACS>100, 399 cases). Independent-sample t-tests, Mann-Whitney U tests, or χ2 tests were employed to analyze the differences in clinical data and lumbar vBMD between the two groups. Binary logistic regression was employed to control confounding factors and analyze the correlation between lumbar vBMD and moderate-to-severe CAC. Multivariate binary logistic regression was used to identify independent predictors of moderate-to-severe CAC and construct a combined prediction model. The receiver operating characteristic curve was used to evaluate the efficacy of lumbar vBMD and the combined model in predicting moderate-to-severe CAC. The comparison of the area under the curve (AUC) was conducted using the DeLong test. Results:The age, incidence of diabetes, hypertension, and osteoporosis were significantly higher in the moderate-to-severe calcification group than in the low calcification group, while lumbar vBMD was significantly lower in the former group (all P<0.05). The body mass index, smoking history, and hyperlipidemia had no statistical differences between the two groups (all P>0.05). Following adjustment for potential confounding variables, the results of binary logistic regression analysis revealed that lumbar vBMD was not significantly associated with the presence of moderate-to-severe CAC in the overall study population or in male ( OR=0.998, 95% CI 0.993-1.003, P=0.379; OR=1.000, 95% CI 0.993-1.006, P=0.918). However, lumbar vBMD was a statistically significant predictor in females ( OR=0.992, 95% CI 0.985-0.999, P=0.032). Multivariate binary logistic regression analysis further demonstrated that age ( OR=1.048, 95% CI 1.019-1.077, P=0.001), hypertension ( OR=2.649, 95% CI 1.719-4.082, P<0.001), and lumbar vBMD ( OR=0.992, 95% CI 0.984-0.999, P=0.022) were independent predictors of moderate-to-severe CAC in women. The AUC of lumbar vBMD for predicting moderate-to-severe CAC in female patients was 0.684 (95% CI 0.641-0.725), and the AUC of the combined model was 0.746 (95% CI 0.705-0.784), with a statistically significant difference ( Z=3.26, P=0.001). Conclusions:Lumbar vBMD measured by QCT is an independent predictor of moderate-to-severe CAC in women and demonstrates moderate predictive value. The predictive performance can be enhanced by integrating age and hypertension into a combined predictive model.

Objective:To investigate the related factors for unexpected positive intraoperative cultures (UPC) in patients undergoing aseptic hip revision and the long-term prosthesis survival rate in such patients.Methods:A retrospective cases series analysis was conducted in 397 patients who underwent aseptic hip revision surgery at the Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University from January 2012 to December 2021. There were 225 females and 172 males with an age ( M(IQR)) of 58(23) years (range:21 to 89 years) and a body mass index (BMI) of 25(6) kg/m 2 (range:15 to 39 kg/m 2). Based on the culture results of intraoperative specimens, patients were divided into culture-positive group (32 cases) and culture-negative group (365 cases). The clinical data were analyzed including gender, age, BMI, preoperative C-reactive protein, preoperative erythrocyte sedimentation rate, American Society of Anesthesiologists(ASA) classification, preoperative urinary bacteria, preoperative hypoproteinemia; comorbidities of diabetes mellitus, anemia, chronic obstructive pulmonary disease, cerebral infarction; history of allergy to antibiotics, smoking, drinking, previous prosthetic dislocation, previous surgical intervention; and time from symptom onset to admission, duration of surgery, etc. A univariate analysis was performed by Mann-Whitney U orχ2 test and the independent risk factors were identified by including the independent variables with P<0.20 in the univariate analysis in a logistic regression analysis of dichotomous variables. The study outcomes were defined as :(1) re-surgical treatment for any reason; (2)symptoms of infection such as sinus and incision seepage; (3) persistent excessive hip pain.The Kaplan-Meier survival curve was plotted using the study outcome of any cause as the endpoint event, and the log-rank test was used to compare the 10-year survival rate of the prosthesis in the culture-negative group with that in the culture-positive group. Results:Univariate analysis showed statistically significant differences between the culture-negative and culture-positive groups when comparing gender, BMI, ASA classification, and preoperative urinary bacterial results ( χ2=2.368, P=0.124; χ2=-1.648, P=0.098; χ2=14.128, P=0.003; and χ2=7.384, P=0.007). Logistic regression analysis showed that male, ASA classification Ⅳ, and positive preoperative urinary bacteria were independent risk factors for the development of UPC during aseptic hip revision( OR=2.35,95% CI:1.08 to 5.36, P=0.040; OR=37.32,95% CI:1.80 to 1 810.63, P=0.030; OR=4.11,95% CI:1.40 to 11.12, P=0.012). The follow-up time of the 397 patients included in this study was 70 (134) months (range:12 to 146 months). The Kaplan-Meier survival curves showed that the 10-year survival rates of the prostheses in the culture-negative and culture-positive groups were 95.7% and 75.0%, respectively. There was no statistically significant difference in the 10-year survival rate comparing the two groups ( P=0.661). Conclusions:UPC is more likely to occur in patients undergoing hip revision due to noninfectious factors in those who are male, have positive preoperative urinary bacteria, and have an ASA classification of Ⅳ. Intraoperative specimen culture results (negative or positive) do not affect 10-year prosthesis survival rate after hip revision.

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.

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.

Objective:To explore the value of lumbar volumetric bone mineral density (vBMD) measured by quantitative computed tomography (QCT) in predicting coronary artery calcification (CAC).Methods:This retrospective, cross-sectional study included a total of 991 patients (504 male and 487 female) who underwent coronary artery CT angiography (CTA) and chest, abdomen, or lumbar spine CT examinations at Taihe County People′s Hospital from January 2023 to June 2024. Lumbar vBMD was measured by QCT. The coronary artery calcification score (CACS) was calculated using an artificial intelligence-assisted diagnostic system. Patients were categorized into a low calcification group (CACS≤100, 592 cases) and a moderate-to-severe calcification group (CACS>100, 399 cases). Independent-sample t-tests, Mann-Whitney U tests, or χ2 tests were employed to analyze the differences in clinical data and lumbar vBMD between the two groups. Binary logistic regression was employed to control confounding factors and analyze the correlation between lumbar vBMD and moderate-to-severe CAC. Multivariate binary logistic regression was used to identify independent predictors of moderate-to-severe CAC and construct a combined prediction model. The receiver operating characteristic curve was used to evaluate the efficacy of lumbar vBMD and the combined model in predicting moderate-to-severe CAC. The comparison of the area under the curve (AUC) was conducted using the DeLong test. Results:The age, incidence of diabetes, hypertension, and osteoporosis were significantly higher in the moderate-to-severe calcification group than in the low calcification group, while lumbar vBMD was significantly lower in the former group (all P<0.05). The body mass index, smoking history, and hyperlipidemia had no statistical differences between the two groups (all P>0.05). Following adjustment for potential confounding variables, the results of binary logistic regression analysis revealed that lumbar vBMD was not significantly associated with the presence of moderate-to-severe CAC in the overall study population or in male ( OR=0.998, 95% CI 0.993-1.003, P=0.379; OR=1.000, 95% CI 0.993-1.006, P=0.918). However, lumbar vBMD was a statistically significant predictor in females ( OR=0.992, 95% CI 0.985-0.999, P=0.032). Multivariate binary logistic regression analysis further demonstrated that age ( OR=1.048, 95% CI 1.019-1.077, P=0.001), hypertension ( OR=2.649, 95% CI 1.719-4.082, P<0.001), and lumbar vBMD ( OR=0.992, 95% CI 0.984-0.999, P=0.022) were independent predictors of moderate-to-severe CAC in women. The AUC of lumbar vBMD for predicting moderate-to-severe CAC in female patients was 0.684 (95% CI 0.641-0.725), and the AUC of the combined model was 0.746 (95% CI 0.705-0.784), with a statistically significant difference ( Z=3.26, P=0.001). Conclusions:Lumbar vBMD measured by QCT is an independent predictor of moderate-to-severe CAC in women and demonstrates moderate predictive value. The predictive performance can be enhanced by integrating age and hypertension into a combined predictive model.

Objective:To investigate the related factors for unexpected positive intraoperative cultures (UPC) in patients undergoing aseptic hip revision and the long-term prosthesis survival rate in such patients.Methods:A retrospective cases series analysis was conducted in 397 patients who underwent aseptic hip revision surgery at the Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University from January 2012 to December 2021. There were 225 females and 172 males with an age ( M(IQR)) of 58(23) years (range:21 to 89 years) and a body mass index (BMI) of 25(6) kg/m 2 (range:15 to 39 kg/m 2). Based on the culture results of intraoperative specimens, patients were divided into culture-positive group (32 cases) and culture-negative group (365 cases). The clinical data were analyzed including gender, age, BMI, preoperative C-reactive protein, preoperative erythrocyte sedimentation rate, American Society of Anesthesiologists(ASA) classification, preoperative urinary bacteria, preoperative hypoproteinemia; comorbidities of diabetes mellitus, anemia, chronic obstructive pulmonary disease, cerebral infarction; history of allergy to antibiotics, smoking, drinking, previous prosthetic dislocation, previous surgical intervention; and time from symptom onset to admission, duration of surgery, etc. A univariate analysis was performed by Mann-Whitney U orχ2 test and the independent risk factors were identified by including the independent variables with P<0.20 in the univariate analysis in a logistic regression analysis of dichotomous variables. The study outcomes were defined as :(1) re-surgical treatment for any reason; (2)symptoms of infection such as sinus and incision seepage; (3) persistent excessive hip pain.The Kaplan-Meier survival curve was plotted using the study outcome of any cause as the endpoint event, and the log-rank test was used to compare the 10-year survival rate of the prosthesis in the culture-negative group with that in the culture-positive group. Results:Univariate analysis showed statistically significant differences between the culture-negative and culture-positive groups when comparing gender, BMI, ASA classification, and preoperative urinary bacterial results ( χ2=2.368, P=0.124; χ2=-1.648, P=0.098; χ2=14.128, P=0.003; and χ2=7.384, P=0.007). Logistic regression analysis showed that male, ASA classification Ⅳ, and positive preoperative urinary bacteria were independent risk factors for the development of UPC during aseptic hip revision( OR=2.35,95% CI:1.08 to 5.36, P=0.040; OR=37.32,95% CI:1.80 to 1 810.63, P=0.030; OR=4.11,95% CI:1.40 to 11.12, P=0.012). The follow-up time of the 397 patients included in this study was 70 (134) months (range:12 to 146 months). The Kaplan-Meier survival curves showed that the 10-year survival rates of the prostheses in the culture-negative and culture-positive groups were 95.7% and 75.0%, respectively. There was no statistically significant difference in the 10-year survival rate comparing the two groups ( P=0.661). Conclusions:UPC is more likely to occur in patients undergoing hip revision due to noninfectious factors in those who are male, have positive preoperative urinary bacteria, and have an ASA classification of Ⅳ. Intraoperative specimen culture results (negative or positive) do not affect 10-year prosthesis survival rate after hip revision.

To investigate the prevalence and epidemiological characteristics of diabetic retinopathy (DR) in Yunnan Province, explore its risk factors, and provide a basis for the prevention and treatment of chronic complications of diabetes mellitus (DM). This is a large cross-sectional study, in all, 1 524 DM patients in 16 communities and villages of Yunnan Province who were registered in health service centers were included in this study from August to November 2019. All patients completed a uniform questionnaire, anthropometric measurements, biochemical measurements, and auxiliary examinations. Logistic regression analysis was used to screen the risk factors of DR. The prevalence rates of DR, mild non-proliferative DR (mild-NPDR), and referable DR (RDR) were 16.0% (244/1 524), 4.5% (69/1 524), and 11.5% (175/1 524), respectively. Glycated hemoglobin A 1c (HbA 1c)≥7.0% was the risk factor of mild-NPDR ( OR=1.872, 95% CI 1.055-3.323) and RDR ( OR=4.821, 95% CI 2.917-7.969). Blood pressure≥130/80 mmHg (1 mmHg=0.133 kPa) was the risk factor of mild-NPDR ( OR=1.933, 95% CI 1.112-3.358) and RDR ( OR=1.505, 95% CI 1.063-2.130). In Yunnan Province, 16.0% DM patients had accompanying DR, wherein about 71.7% of them required an ophthalmology referral, and the high incidence of RDR in DM patients was associated with poor control of blood glucose and blood pressure.

Objective:To explore the optimal acceleration factor and feasibility of the compressed SENSE (CS) technique in non-contrast MR coronary angiography (NMRCA) for clinical practice.Methods:The image data of completed coronary CTA and 3.0 T NMRCA sequence in 31 patients with suspected coronary heart disease were prospectively recruited at Fuyang People′s Hospital from August 2021 to November 2021. NMRCA sequences included conventional SENSE2 sequence and CS sequences with acceleration factors of 4, 5, and 6, respectively. The subjective scores of image quality and the objective scores, the contrast ratios between assessed coronaries and myocardium (CMCR) were compared among the 4 groups using the Friedman and Wilcoxon rank sum test.Results:Compared with the conventional SENSE2 [(343±46)s], the scan time of CS4 (269±36), CS5 (214±29) and CS6 (178±26) s were shortened by 21.5%, 37.5% and 48.0%, respectively. There was a good consistency between the subjective scores of the four groups (Kappa=0.769, 95% Cl 0.738-0.800). There was no significant difference in subjective score and CMCR value between CS4 and SENSE2 ( P>0.05). The coronary artery segments of CS5 and CS6 were significantly different from SENSE2 group ( P<0.05). Conclusions:For 3.0 T NMRCA, CS technology shows high feasibility. The CS4 can reduce imaging time while ensuring high-quality coronary arterial images, which has a well-established clinical application value for NMRCA.

Objective To investigate the situation of drinking water fluorosis in Tianjin, to study the benchmark dose of urinary fluoride, and to provide a reference for the formulation of the standard for urinary fluoride. Methods Three fluorosis endemic areas were selected in Tianjin, and three villages in each area were selected in this study. The water fluoride was detected, and the prevalence of dental fluorosis and the urinary fluoride of children aged 8-12 years old were investigated. Results The prevalence of dental fluorosis and urinary fluoride content in children in the villages with water fluoride exceeding the standard were significantly higher than those in the villages with water fluoride qualified, and the difference was statistically significant (χ²=88.821, P＜0.001; Z=6.089, P＜0.001). The analysis of the prevalence of dental fluorosis in children showed that the younger the age, the lower the prevalence and severity of dental fluorosis (χ²_trend=14.584, P<0.001; χ²_trend= 20.525, P<0.001). There were no significant differences in the prevalence and severity of dental fluorosis among children of different genders (χ²=0.736, P=0.391; χ²=3.649, P=0.456). There were significant differences in urinary fluoride between children with different ages and genders (H=14.768, P=0.011; Z=-2.526, P=0.012). According to the level of urinary fluoride, the children were divided into 5 groups. With the increase of urinary fluoride concentration, the prevalence of dental fluorosis gradually increased and the difference was statistically significant (χ²_trend=16.348, P<0.001), showing a dose-effect relationship. Based on the prevalence of dental fluorosis in children, BMDS was used to calculate the BMD and BMDL, which were 2.20 mg/L and 1.54 mg/L, respectively. Conclusion The water reform and fluoride reduction in Tianjin has achieved certain results. There is a dose-effect relationship between urinary fluoride and prevalence of dental fluorosis in children, and the reference dose value is slightly higher than the current standard, suggesting that the current standard can be updated timely.