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.

Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)₂-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)₂-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)₂-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)₂-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)₂-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.

Objective:To explore the relationship between drug literacy and quality of life in patients with multiple chronic diseases.Methods:It was a cross-sectional study. Between March and October 2023, 260 patients with multiple chronic diseases from the General Medicine Department of Peking University Third Hospital were selected using a convenience sampling method. A medication literacy scale, a medication adherence scale, and a health survey scale (SF-36 scale) were used to conduct a questionnaire survey in the patients. The SF-36 scale reflected the quality of life of the patients (including physical health and mental health). A total of 260 questionnaires were distributed, 260 questionnaires were returned, and 240 were effective (92.3%). Single-factor analysis of medication literacy in those patients was conducted using F-test and t-test. The correlation between medication literacy and medication adherence, as well as between medication literacy and quality of life, was analyzed using Pearson′s test. The correlation between different factors and medication adherence, as well as quality of life, in those patients was analyzed using multiple linear regression. Results:Among the 240 patients with multiple chronic diseases, 134 were male and 106 were female, aged (65.84±11.56) years. The drug literacy scale score was (8.36±3.57) points, the SF-36 physical health score was (242.00±87.85) points, mental health score was (275.67±80.29) points, medication compliance scale score was (6.22±1.93) points. The drug literacy was positively correlated with medication compliance ( r=0.157) and mental health ( r=0.165) in patients with multiple chronic diseases (all P<0.05). The score of drug literacy ( SE=2.440), mental health score ( SE=2.523), perceptual impairment ( SE=2.046) and duration of disease ( SE=2.459) were positively correlated with the medication compliance of the patients, while the number of chronic diseases ( SE=-2.818) was negatively correlated with the medication compliance of the patients (all P<0.05). The score of drug literacy ( SE=0.121) and insensible perception disorder ( SE=0.399) were positively correlated with the quality of life of the patients, and the number of chronic diseases ( SE=-0.171) was negatively correlated with the quality of life of the patients (all P<0.05). Conclusion:The drug literacy of patients with multiple chronic diseases is at the medium level, and the drug literacy is positively correlated with medication compliance and quality of life.

Objective:To investigate the operation of water improvement projects in villages affected by drinking-water-borne endemic arsenic poisoning in Shaanxi Province, the arsenic level in both internal and external environments, the trend of disease development and patient management, and evaluate the effectiveness of prevention and control measures.Methods:From March to December 2023, in accordance with the requirements of the "Notice of the Office of Shaanxi Provincial Health Commission on Issuing the Monitoring Plan for Key Endemic Diseases such as Kashin-Beck Disease" and the "Monitoring Plan for Endemic Fluorosis and Arsenism in Shaanxi Province", all villages affected by drinking-water-borne arsenic disease were monitored. Water arsenic testing was carried out in accordance with the "Standard Test Methods for Drinking Water Inorganic Nonmetallic Indicators" (GB/T 5750.5-2006), and the evaluation of whether water arsenic exceeded the standard was conducted based on the "Sanitary Standards for Drinking Water" (GB 5749-2022). According to the "Diagnosis of Endemic Arsenism" (WS/T 211-2015), the arsenic poisoning status of all population in the disease affected areas was investigated. In 5 villages of 3 monitoring counties, 358 people were randomly selected to determine the urinary arsenic level, and the determination was made according to the "Safety Guideline Value of Urinary Arsenic for Human Population" (WS/T 665-2019). According to the "Notice of the National Health Commission on Issuing the Evaluation Measures for Control and Elimination of Key Endemic Diseases (2019 Edition)", elimination evaluation was conducted.Results:A total of 2 cities, 3 counties, 9 towns, and 13 endemic villages were monitored, with a water improvement rate of 100% (13/13), and all were operating normally. The arsenic level in residents' drinking water was < 0.01 mg/L. A total of 12 688 people were examined, and 338 cases of arsenic poisoning were detected, all of whom were historical cases. There were no new cases of arsenic poisoning or skin cancer patients. The geometric mean of urinary arsenic was 0.026 0 mg/L, which was lower than the safety guideline value of 0.032 mg/L for urinary arsenic in the population. All 338 existing arsenic poisoning patients had received family doctor contract services and implemented follow-up management. The drinking-water-borne endemic arsenic poisoning areas counties in Shaanxi Province have reached the elimination standard.Conclusions:The water improvement project in drinking-water-borne endemic arsenic poisoning areas in Shaanxi Province is operating normally. The arsenic content in both the internal and external environments of the population meets the standard. The condition is stable and no new cases have been detected. Follow up management has been implemented for all current cases. All affected counties have reached the elimination standard.

ObjectiveTo understand the infection characteristics and drug resistance of carbapenem-resistant Serratia marcescens (CRSM) in a general hospital in Shanghai, and to provide a theoretical basis for clinical anti-infective treatment and prevention of drug-resistant bacteria. MethodsClinical data on cases with CRSM infections detected in clinical specimens at a gradeⅢ level A general hospital in Shanghai from June 2022 to June 2024 were retrospectively collected, and their clinical distributions, factors of hospital-acquired infections, prognosis, and drug-resistant situation were analyzed simultaneously. ResultsA total of 38 cases with CRSM were detected from June 2022 to June 2024, and the number of CRSM strains accounted for 25.00% (38/152) of the number of SM strains. The 38 CRSM infection samples were all derived from sputum. CRSM were distributed in 9 clinical departments, and the top 3 departments having the highest percentages of CRSM among SM strains, were intensive care unit (ICU) (78.79%, 26/33), gastrointestinal surgery department (57.14%, 4/7), and thyroid hernia surgery department (50.00%, 1/2). Among the 38 patients with CRSM infections, 8 cases were identified as hospital-acquired infection, resulting in a hospital-acquired infection rate of 21.05. The mortality rate of the 38 cases of CRSM infected patients within 30 days after detection of CRSM was 23.68% (9/38). The results of multivariate logistic regression analysis showed that sequential organ failure assessment (SOFA) score ≥6.5 points (OR=15.33, P<0.001), septic shock (OR=4.85, P=0.032), and suffering from neoplastic diseases (OR=0.12, P=0.018) were the related factors for death within 30 days after the detection of CRSM in patients with CRSM infection. The results of drug sensitivity test showed that the 38 cases of CRSM exhibited 100.00% (38/38) sensitivity to trimethoprim/sulfamethoxazole, tigecycline, or ceftazidime/avibactam; demonstrated high resistance toβ-lactams except for ceftazidime (18.42%, 7/38), the latter of which was one of the third-generation of cephalosporins; showed elevated resistance to fluoroquinolones [levofloxacin (89.47%, 35/38), ciprofloxacin (94.74%, 36/38)]; maintained good tetracycline sensitivity [doxycycline (97.37%, 37/38), minocycline (76.32%, 29/38)]; and displayed high susceptibility to the aminoglycoside gentamicin (94.74%, 36/38) and elevated resistance to tobramycin (86.84%, 34/38). The detection rate of serine carbapenemase in the 38 strains of CRSM was 100.00%, while all strains tested negative for metallo-β-lactamases. ConclusionFrom June 2022 to June 2024, the detection rate of CRSM in a gradeⅢ level A general hospital in Shanghai was relatively high, especially in the ICU. CRSM has a high resistance rate to commonly used antibacterial drugs such as the first and second-generation cephalosporins, quinolones, and polypeptide antibacterial drugs. Therefore the dynamics of drug-resistant bacteria should be tracked in a timely manner to guide the rational clinical application of antibacterial drugs.

OBJECTIVE To construct three-class （insufficient， normal， excessive） and two-class （insufficient， normal） models for predicting plasma concentration of valproic acid （VPA）， and compare the performance of these two models， with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 （a total of 695 sets of data）. In this study， predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation， and the performance of the models was evaluated using three indexes: accuracy， F1 score， and the area under the working characteristic curve of the subject （AUC）. RESULTS XGBoost feature importance scores revealed that in the three-class model， the importance ranking of kidney disease and electrolyte disorders was higher. However， in the two-class model， the importance ranking of these features significantly decreased， suggesting a close association with the excessive blood concentration of VPA. In the three-class model， Random Forest method performed best， with F1 score of 0.704 0 and AUC of 0.519 3 on the test set； while in the two-class model， CatBoost method performed optimally， with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration， but its prediction and model generalization abilities are poor； the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases， but its model performance is stronger.

Objective To analyze the influencing factors of preeclampsia(PE)complicated with renal impairment and construct a prediction model.Methods The clinical materials of 300 PE patients with antenatal examination in the hospital from January 2020 to January 2023 were retrospec-tively collected and divided into modeling set of 200 cases and validation set of 100 cases by a random number table in a ratio of 2 to 1.All the patients were followed up for 3 months after delivery.Pa-tients in the modeling set with renal impairment were included in occurrence group,and the rest were included in non-occurrence group.Clinical materials between the modeling set and the validation set as well as between the occurrence group and the non-occurrence group within the modeling set were compared.Logistic regression analysis was conducted to identify the influencing factors of renal im-pairment in PE and construct a prediction model.The model performance was evaluated by the receiv-er operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results There was no significant difference in clinical data between the modeling set and validation set(P＞0.05).After completion of follow-up for 300 PE patients,renal impairment occurred in 75 cases(25.00％),including 24 cases(24.00％)in the validation set and 51 cases(25.50％)in the modeling set.A total of 51 patients with renal impairment in the modeling set were included in the occurrence group,and the remaining 149 patients were included in the non-occurrence group.Com-pared with the non-occurrence group,the occurrence group had significant older age,higher propor-tions of HELLP syndrome,early-onset PE and severe manifestations of PE,increased systolic blood pressure,diastolic blood pressure,resistance index(RI)and pulsatility index(PI)of renal interlo-bar artery as well as decreased peak systolic velocity(PSV)and end-diastolic velocity(EDV)of re-nal interlobar artery and platelet(PLT)(P＜0.05).Logistic regression analysis showed that age,HELLP syndrome,early-onset of PE,severe manifestations of PE,and RI of renal interlobar artery were influencing factors of renal impairment in PE(P＜0.05).A prediction model for renal impair-ment in PE was established based on the results of Logistic regression analysis in the modeling set.The area under the curve(AUC)of this model for predicting renal impairment was 0.949(95％CI,0.917 to 0.971)in the modeling set and 0.944(95％CI,0.900 to 0.972)in the validation set.Calibration curves for the modeling set and validation set were plotted,and the Hosmer-Lemeshow test showed no significant differences(P＞0.05).Internal validation by the Bootstrap method showed consistency index was 0.913(95％CI,0.828 to 0.998)for the modeling set and 0.907(95％CI,0.840 to 0.974)for the validation set.According to DCA,the clinical net benefit of the prediction model was obtained at risk thresholds of 0.13 to 0.92 for the modeling set and 0.18 to 0.87 for the validation set.Conclusion The influencing factors of renal impairment in PE include age,HELLP syndrome,early-onset of PE,severe manifestations of PE,and RI of renal interlobar artery.The prediction model established based on these factors demonstrates good performance in predicting renal impairment in PE,providing evidences for clinical assessment of renal impairment risk in PE.

OBJECTIVE To carry out regular monitoring of carbapenem-resistant Klebsiella pneumoniae(CRKP)contamination status in the environment of intensive care unit(ICU)and take targeted prevention and control measures so as to reduce the incidence of hospital-associated infections with multidrug-resistant organisms(MDROs).METHODS The surfaces of surroundings of the patients who were colonized and infected with CRKP in the ICU of grade A tertiary hospital of Shanghai and the hands of relevant staff were sampled by stages from Jan 1,2021 to Jun 30,2024.The distribution of the CRKP strains in the surroundings were analyzed according to the locations positive for CRKP,and the disinfection measures were accordingly and continuously modified.The trend of isolation rate of CRKP strains from the ICU patients was analyzed during the time period when the measures were implemented.RESULTS Totally 266 environmental samples were collected during the baseline period(from Jan.1 2021 to Dec.31 2021),265 during intervention period(from Jan.1 2022 to Dec.31 2023),274 during con-solidation period(from Jan.1 to Jun.30 2024);the isolation rates of the CRKP strains were 4.51％,4.91％and 3.65％,respectively.The isolation rate of the strains was highest from the bed unit(10.40％),followed by the article for public use(6.74％),articles used by health care workers(2.98％)and diagnosis and treatment arti-cles(1.91％).The isolation rate of CRKP of the patients was 24.75％during the baseline period,15.48％during the intervention period,5.69％during the consolidation period,showing a continuously downward trend(x2=30.330,P＜0.001).CONCLUSION It is necessary to regularly carry out the environmental monitoring of CRKP strains,seek for the weak links of environmental disinfection and implement the intensified prevention and control measures so as to reduce the incidence of CRKP infection,which may provide theoretical bases for effective control of the CRKP strains.

Objective To investigate whether PKCβ inhibitor can alleviate RIRI by regulating macrophage phenotype.Methods Rats in the renal ischemia-reperfusion injury(RIRI)model group underwent right nephrec-tomy followed by a 60-minute clamping of the left renal pedicle.In the experimental group(Inhibitor+RIRI),PKCβ inhibitors were administered orally one day prior to surgery.All rats were euthanized 24 hours post-surgery for the collection of blood and left kidney samples.Renal function,tissue morphology,and the expression levels of renal tubular injury marker KIM-1,renal papilla injury marker RPA-1,macrophage subtype markers,and inflammatory factors were evaluated.Results PKCβ inhibitors alleviated renal ischemia-reperfusion injury in rats.PAS staining revealed marked tubular damage in kidney sections from the RIRI group,whereas kidney inflammatory cell infiltra-tion and renal tubular injury scores were significantly reduced in the Inhibitor+RIRI group following PKCβ inhibitor treatment(all P<0.05).The expression levels of Cr,BUN,KIM-1,and RPA-1 were markedly elevated in the RIRI group compared to the Sham and Inhibitor+RIRI groups(all P<0.05).After PKCβ inhibitor intervention,the expression levels of Cr,BUN,KIM-1,and RPA-1 were significantly decreased in the Inhibitor+RIRI group relative to the RIRI group(all P<0.05).Protein expression levels of iNOS,IL-2,and CD197 in the kidney tissue of the RIRI group were significantly higher than those in the Sham and Inhibitor+RIRI groups(all P<0.05).Compared with the RIRI group,the protein expression levels of iNOS,IL-12,and CD197 were significantly reduced in the Inhibitor+RIRI group following PKC β inhibitor intervention(all P<0.05).Additionally,the protein expression levels of Dectin-1,ARG-1,and CD163 were significantly higher in the Inhibitor+RIRI group than in the RIRI and Sham groups after PKCβ inhibitor intervention(all P<0.05).Conclusions PKCβ inhibitors can mitigate renal dysfunction,renal tubular injury,and the expression of injury markers in the renal tubules and renal papilla follow-ing ischemia-reperfusion.Additionally,PKCβ inhibitors play a role in modulating macrophage subtypes by reducing M1 macrophages and promoting polarization to M2,which leads to a decrease in pro-inflammatory factors and an increase in anti-inflammatory factors,ultimately facilitating kidney repair.

Objective:To investigate the diagnostic value of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for biopsy-negative esophageal strictures suspected for malignancy.Methods:Patients who underwent EUS-FNA for esophageal strictures with negative endoscopic biopsies in Nanjing Drum Tower Hospital from January 2014 to March 2022 were analyzed retrospectively. The final diagnosis was based on the pathological outcomes of EUS-FNA or surgery, complemented by follow-up data. Diagnostic efficacy and complication rates of EUS-FNA were analyzed.Results:A total of 64 patients were included in this study,with 54 ultimately diagnosed with malignant lesions and 10 with benign lesions. Malignant lesions were diagnosed by EUS-FNA in 50 cases, suspected malignant lesions in 3 cases, and no clear basis for malignancy was observed in 11 cases. The diagnostic accuracy of EUS-FNA was 98.4% (63/64), with the malignant tumor detection rate of 98.1% (53/54). No post-procedure complications such as bleeding, perforation, or infection were observed in any patient.Conclusion:EUS-FNA is safe and effective for the diagnosis of biopsy-negative suspected malignant esophageal stricture with a high malignant lesion detection rate.