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 evaluate a third-generation applicator template for intracavitary combined with interstitial brachytherapy(IC-ISBT)suitable for locally advanced cervical cancer,aiming to improve therapeutic outcomes.[Methods]A retrospective study was conducted on patients with stage IB3-ⅣB cervical cancer treated at Sun Yat-sen University Cancer Center from January 2023 to October 2023.Magnetic resonance imaging data before and after external beam radiation therapy were collected and analyzed.According to the residual tumor after external beam radiation,high-risk clinical target volumes(HR-CTV)were delineated,based on which a third-generation IC-ISBT applicator template was designed.The dosimetric and therapeutic differences between using this applicator template(template implantation group)and traditional freehand interstitial implantation(freehand implantation group)were further compared.Statistical methods were used to analyze the data from both groups to test the efficacy and safety of the two approaches.[Results]The third-generation applicator template could accommodate different cervical structures and optimize needle path layout.The tumor volume in the template implantation group was significantly larger than in the freehand implantation group,showing statistical differences.In terms of dosimetric coverage(V100%),the template implantation group exhibited significant statistical differences compared with the freehand implantation group,demonstrating superior dose coverage.Additionally,the third-generation template showed advantages in protecting the rectum and sigmoid colon by potentially reducing high-dose points,while there were no significant differences in bladder dosimetry between the two methods.The primary cervical lesion remission rates were similar between the two groups.[Conclusion]The third-generation IC-ISBT applicator template is scientifically and rationally designed,especially for patients with larger tumor volumes and later stages.It is easy to operate,highly reproducible,and shows significant advantages in dose distribution and protection of surrounding critical organs.The template has the potential to be widely applied as a routine treatment option.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To investigate the protective effects of Ligilactobacillus salivarius Li01(L.salivarius Li01)against DNA damage induced by Helicobacter pylori(Hp),Benzo(a)pyrene(BaP),and Hp+BaP,and to evaluate the probiotic properties of L.salivarius Li01.Methods After 1 week of adaptive feeding,specific pathogen-free male Mongolian gerbils were randomly assigned to groups and subjected to intragastric administration of Hp,BaP,and Hp+BaP for model induction.At week 32 post model establishment,therapeutic L.salivarius Li01 was administered intragastrically.At week 36,peripheral blood samples were collected from each group for the comet assay,while liver tissues were collected and tested for Cyp1a1 gene expression levels.Results Compared with those in the control group,the comet tail length,％tail DNA,and hepatic Cyp1a1 expression levels were significantly increased in the Hp,BaP,and Hp+BaP groups(P＜0.0001).Among these,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly higher in the Hp+BaP group than in the Hp and BaP groups(P＜0.05).Following intervention with L.salivarius Li01,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly reduced in each group(P＜0.001).Conclusions Hp infection,BaP exposure,and the Hp+BaP combination induced DNA damage in the peripheral lymphocytes of Mongolian gerbils,with the Hp+BaP combination showing synergistic damage.L.salivarius Li01 had a protective effect against DNA damage caused by Hp,BaP,and Hp+BaP.

Objective:To construct univariate and multivariate relapse free survival (RFS) prediction models for breast cancer patients with diabetes mellitus type 2 (T2DM) and to compare and select the model with higher predictive performance.Methods:A total of 912 breast cancer patients treated at the First Affiliated Hospital of Dalian Medical University from January 2010 to December 2016 were included, of which 202 patients had T2DM and 710 patients did not. Kaplan-Meier survival curve was drawn based on whether patients had T2DM, and log-rank test was performed based on whether patients had T2DM. All patients were randomly divided into a training set ( n=640) and a validation set ( n=272) at a ratio of 7∶3. Univariate and multivariate Cox proportional risk regression models were used to analyze RFS in breast cancer patients with the survival package. The "rms" package was employed to construct univariate and multivariate RFS prediction models for breast cancer patients with T2DM. Clinical decision curves and calibration curves were used to validate the models. The receiver operator characteristic (ROC) curve was used to compare and analyze the prediction performance of the two models. Results:There were no statistically significant differences between the training set and the validation set patients in terms of age, T2DM, surgical approach, axillary management methods, T stage, N stage, molecular sub-type, estrogen receptor (ER) 1, ER2, progesterone receptor (PR) , ER and PR consistency, Ki67, human epidermal growth factor receptor 2 (HER2) (all P>0.05) . There was a statistically significant difference in histological grade ( χ2=7.59, P=0.022) . Survival analysis showed that the 5-year RFS rate was 83.7% in patients with T2DM and 92.3% in patients without T2DM ( χ2=16.61, P<0.001) . Univariate analysis revealed that age ( HR=1.04, 95% CI: 1.03-1.06, P<0.001) , T2DM ( HR=2.31, 95% CI: 1.49-3.55, P<0.001) , surgical approach ( HR=2.39, 95% CI: 1.20-4.77, P=0.013) , axillary management methods ( HR=2.62, 95% CI: 1.72-3.98, P<0.001) , T stage (T 2: HR=2.13, 95% CI: 1.36-3.31, P<0.001; T 3: HR=6.90, 95% CI: 3.35-14.22, P<0.001) , N stage (N 2: HR=3.87, 95% CI: 2.12-7.07, P<0.001; N 3: HR=8.61, 95% CI: 4.71-15.75, P<0.001) , molecular sub-type (Luminal B: HR=2.74, 95% CI: 1.17-6.36, P=0.019; HER2 +: HR=3.64, 95% CI: 1.38-9.58, P=0.009; TNBC: HR=4.40, 95% CI: 1.71-11.34, P=0.002) , ER1 (>10%: HR=0.57, 95% CI: 0.37-0.90, P=0.016) , ER2 ( HR=0.57, 95% CI: 0.37-0.89, P=0.015) , and PR ( HR=0.56, 95% CI: 0.37-0.86, P=0.008) were all factors influencing RFS in breast cancer patients. Multivariate analysis demonstrated that age ( HR=1.04, 95% CI: 1.02-1.06, P<0.001) , T2DM ( HR=1.82, 95% CI: 1.16-2.85, P=0.009) , T stage (T 2: HR=1.60, 95% CI: 1.01-2.54, P=0.046; T 3: HR=2.64, 95% CI: 1.22-5.72, P=0.014) , N stage (N 2: HR=3.72, 95% CI: 2.01-6.88, P<0.001; N 3: HR=5.34, 95% CI: 2.78-10.25, P<0.001) , and ER1 (>10%: HR=0.63, 95% CI: 0.39-0.99, P=0.046) were independent factors influencing RFS in breast cancer patients. Based on the 10 and 5 variables with P<0.05 in the univariate and multivariate analyses respectively, the nomograms of the univariate and multivariate prediction models were constructed to evaluate the influence of factors such as T2DM on the postoperative RFS of breast cancer patients. Clinical decision curves and calibration curves indicated that both models had high predictive value for RFS in breast cancer patients, and the predictive results were highly consistent with the actual observed results. ROC curve analysis showed that there was no statistically significant difference in the area under the curve (AUC) of the two models for predicting the RFS rates of breast cancer patients in the training set and validation set at 36, 60, and 84 months (all P>0.05) , indicating that the predictive efficacy of the two models was comparable. The multivariate model is more suitable for clinical application because it uses fewer variables. Conclusions:Breast cancer patients with T2DM have poorer prognosis. Age, T2DM, T stage, N stage, and ER1 are independent factors influencing postoperative RFS in breast cancer patients. The multi-factor prediction model of RFS in breast cancer patients based on T2DM is more suitable for clinical application due to its higher predictive efficacy and fewer variables.

Objective To investigate the clinical and CT findings features of nonaneurysmal perimesencephalic subarachnoid hem-orrhage(NAPSAH).Methods A retrospective analysis was conducted on 19 cases of NAPSAH confirmed by clinical treatment and follow-up,and their clinical and CT findings features were summarized.Results All patients exhibited mild clinical symptoms and had a good prognosis without complications.The sites of NAPSAH involved the anterior cistern in 17 cases,the suprasellar cistern in 8 cases,the interpeduncular cistern in 7 cases,the anterior cistern only in 1 case,and the suprasellar cistern only in 1 case;Among them,4 cases had vertebrobasilar dolichoectasia(VBD)and 3 cases had tortuous prolongation of vertebrobasilar artery.Conclusion The incidence of NAPSAH is low,the clinical symptoms are mild and good prognosis.It has typical imaging features.Most of its hemorrhage sites are confined to the anterior cistern,suprasellar cistern and interpeduncular cistern.Combining clinical and CT find-ings helpful to improve the accuracy of diagnosis.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To investigate the protective effects of Ligilactobacillus salivarius Li01(L.salivarius Li01)against DNA damage induced by Helicobacter pylori(Hp),Benzo(a)pyrene(BaP),and Hp+BaP,and to evaluate the probiotic properties of L.salivarius Li01.Methods After 1 week of adaptive feeding,specific pathogen-free male Mongolian gerbils were randomly assigned to groups and subjected to intragastric administration of Hp,BaP,and Hp+BaP for model induction.At week 32 post model establishment,therapeutic L.salivarius Li01 was administered intragastrically.At week 36,peripheral blood samples were collected from each group for the comet assay,while liver tissues were collected and tested for Cyp1a1 gene expression levels.Results Compared with those in the control group,the comet tail length,％tail DNA,and hepatic Cyp1a1 expression levels were significantly increased in the Hp,BaP,and Hp+BaP groups(P＜0.0001).Among these,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly higher in the Hp+BaP group than in the Hp and BaP groups(P＜0.05).Following intervention with L.salivarius Li01,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly reduced in each group(P＜0.001).Conclusions Hp infection,BaP exposure,and the Hp+BaP combination induced DNA damage in the peripheral lymphocytes of Mongolian gerbils,with the Hp+BaP combination showing synergistic damage.L.salivarius Li01 had a protective effect against DNA damage caused by Hp,BaP,and Hp+BaP.

ObjectiveTo analyze the expression level of triggering receptor expressed on myeloid cells-1 （TREM-1） in serum and ascites of patients with cirrhotic ascites， and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation. MethodsA total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled， and according to the presence or absence of intra-abdominal infection， they were divided into infection group with 72 patients and non-infection group with 38 patients. The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients. Clinical data and laboratory markers were collected from all patients. Serum and ascites samples were collected， and ELISA was used to measure the level of TREM-1. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between indicators. A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection. The receiver operating characteristic （ROC） curve was used to evaluate the diagnostic and prognostic efficacy of each indicator， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsThe level of TREM-1 in ascites was significantly positively correlated with that in serum （r=0.50， P<0.001）. Compared with the improvement group， the non-improvement group had a significantly higher level of TREM-1 in ascites （Z=-2.391， P=0.017） and serum （Z=-2.544， P=0.011）， and compared with the non-infection group， the infection group had a significantly higher level of TREM-1 in ascites （Z=-3.420， P<0.001）， while there was no significant difference in the level of TREM-1 in serum between the two groups （P>0.05）. The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein （CRP）， procalcitonin （PCT）， white blood cell count， and neutrophil-lymphocyte ratio （r=0.288， 0.344， 0.530， 0.510， 0.534， 0.454， 0.330， and 0.404， all P<0.05）. The ROC curve analysis showed that when PCT， CRP， and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection， the AUCs were 0.715 and 0.740， respectively. The multivariate Logistic regression analysis showed that CRP （odds ratio ［OR］=1.019， 95% confidence interval ［CI］： 1.001‍ ‍—‍ ‍1.038， P=0.043） and serum TREM-1 （OR=1.002， 95%CI： 1.000‍ ‍—‍ ‍1.003， P=0.016） were independent risk factors for the prognosis of patients with cirrhotic ascites and infection， and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis. ConclusionThe level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites， and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.