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.

Purpose To evaluate the diagnostic accuracy of low-iodine contrast subtraction CT pulmonary angiography(CTPA)combined with iodine maps for acute pulmonary embolism(APE),with a focus on detecting subsegmental emboli.Materials and Methods A retrospective analysis included 48 patients with suspected APE who underwent both pulmonary ventilation/perfusion SPECT/CT and low-iodine subtraction CTPA within one week in Beijing Hospital from September 1,2021 to September 1,2024.Using SPECT/CT as the reference standard,the diagnostic performance of subtraction CTPA with iodine maps was assessed.A retrospective review was performed to identify potential causes of false-positive and false-negative results.Results Subtraction CTPA with iodine maps demonstrated high diagnostic accuracy at the segmental and subsegmental pulmonary artery levels,with a sensitivity of 0.917 and specificity of 0.991.At the segmental level,the detection rate was 100%,while at the subsegmental level,it was 66.7%.The method showed consistently high diagnostic performance(83.3%-100%)across different clinical risk stratifications of APE.Retrospective review identified explicable causes for 85.7%(6/7)of false-positive and 33.3%(2/6)of false-negative cases.Conclusion Low-iodine subtraction CTPA combined with iodine maps exhibits robust diagnostic efficacy for APE.Accurate recognition of characteristic perfusion defects on iodine maps may further enhance diagnostic precision.

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 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 prognostic value of triglyceride-glucose index(TyG index)in non-diabetic patients with acute coronary syndrome(ACS)who underwent percutaneous coronary intervention(PCI).Methods A total of 529 non-diabetic ACS patients who had successfully underwent PCI in our hospital from January 2019 to December 2020 were selected.According to the median TyG index(8.98),the patients were divided into low TyG index group(TyG＜8.98)and high TyG index group(TyG≥8.98).All the patients were followed up for major adverse cardiovascular events(MACE).Results Overall,55(10.4％)endpoint events were documented during a 24-month follow-up.Kaplan-Meier survival curves showed that the cumulative incidence of MACE was significantly higher in patients in the high TyG group than in the low TyG group(Log Rank P=0.001).Multivariate Cox analysis showed that after adjusting other confounding factors,TyG index was an independent predictor of MACE(HR=3.50,95％CI:1.44-8.53,P＜0.01).The risk of MACE in the high TyG group was 1.12-fold increased compared with the low TyG group(95％CI:1.19-3.79,P=0.011).The subgroup analysis results were generally consistent.Conclusion TyG index is an independent predictor of MACE in non-diabetic ACS patients who underwent PCI.

OBJECTIVE To explore the isolation rates,drug resistance and molecular epidemiological characteristics of carbapenem-resistant gram-negative bacilli(CRGNB)isolated from intensive care units(ICU)of a tertiary hos-pital so as to provide bases for prevention and control of the nosocomial infections caused by CRGNB.METHODS The environmental surfaces that were high frequently contacted by the patients with CRGNB infections[carbapen-em-resistant Klebsiella pneumoniae(CRKP),carbapenem-resistant Acinetobacter baumannii(CRAB),carbap-enem-resistant Pseudomonas aeruginosa(CRPA)]and their hands were randomly sampled from the ICU of a ter-tiary three-A hospital from Apr.2024 to Aug.2024.Multilocus sequence typing(MLST)and detection of drug re-sistance genes were performed by means of complete genome sequencing technique and bioinformatics,and the ho-mology between the CRGNB strains isolated from the patients and the strains isolated from their surrounding was observed.RESULTS Totally 30(7.85％)strains of CRGNB were isolated,23(6.02％)of which were CRKP,7(1.83％)were CRAB,and no strain of CRPA was detected.The molecular subtyping showed that ST 11(93.33％)was dominant among the CRKP strains,and ST2(69.23％)was dominant among the CRAB strains.The phylogenetic analysis indicated that there were clonal transmission tendencies of CRKP-ST11 and CRAB-ST2.The analysis of drug resistance genes showed that the CRAB strains mainly carried ant(3")-lla(100％),blaOXA-23(92.31％)and amvA(92.31％);blaOXA-23 and blaOXA-66 were the major carbapenems resistance genes;the CRKP strains mainly carried the drug resistance genes emrDh,rmtB1,fosA and kdeA(all were 96.67％),followed by the carbapenems resistance gene blaKPC-2(90.00％).CONCLUSIONS ST11 is the predomi-nant molecular subtype for CRGNB among the CRKP strains isolated from the ICU,anf ST2 predominant among the CRAB strains;the carrying rates of drug resistance genes are high.There is risk of clonal transmission.It is necessary to strengthen the monitoring and take comprehensive infection control measures so as to reduce the incidence of nosocomial infections.

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.