Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

Objective:To explore the risk factors for recurrence of thyroid cancer after radical resection via areola endoscopy,and to construct a visual risk prediction model.Methods:The clinical data of 350 thyroid cancer patients who underwent radical surgery via areola endoscopy in our hospital from January 2016 to October 2018 were retro-spectively analyzed,and they were randomly divided into the modeling group(233 cases)and the internal validation group(117 cases)in a 2:1 ratio.All patients were followed up for 3 years after surgery,and the patients of modeling group were further divided into recurrent group(51)and non recurrent group(182)according to whether they with or not recurrence.Another 163 patients with thyroid cancer who underwent laparoscopic radical mastectomy at our hos-pital from January 2019 to May 2020 were selected as the external validation group.The risk factors for recurrence of thyroid cancer after radical surgery via areola endoscopy was analyzed by using Cox regression method,and a risk prediction nomogram model was established based on this.Internal validation of the nomogram model was conducted by using the Bootstrap method,and the calibration,predictive efficacy and clinical net benefit of the nomogram model were evaluated by the calibration curve,receiver operating characteristic(ROC)curve and decision curve analysis(DCA).The external validation group data was used for external validation.Results:The recurrence rate of thyroid cancer patients after 5 years of radical surgery via areola endoscopy was 21.64％(111/513).The proportions of multiple le-sions,preoperative lymph node metastasis,TNM stages Ⅲ-Ⅳ and maximum tumor diameter,the levels of thyro-globulin(TG),triiodothyronine(T3),thyroxine(T4),free triiodothyronine(FT3),free thyroxine(FT4)and thyroid stimulating hormone(TSH)in the recurrence group were higher than those in the non recurrence group(P<0.05).The Cox regres-sion analysis results showed that the maximum tumor diameter,multiple lesions,preoperative lymph node metasta-sis,TNM stage Ⅲ-Ⅳ and TG,T3,T4,FT3,FT4 and TSH levels were all risk factors for recurrence of thyroid cancer after radical surgery via areola endoscopy(P<0.05).The risk prediction nomogram model of recurrence of thyroid cancer af-ter radical surgery under areola endoscopy was constructed based on the above influencing factors.After internal and external validation,the consistency indices of the modeling group,internal verification group and external verification group were 0.832,0.825 and 0.41 respectively,and the calibration curves of three groups were close to the standard curve.The ROC curve analysis and verification showed that the area under the curve predicted by the nomogram model of the modeling group,internal verification group and external verification group were 0.859,0.847 and 0.853 respectively.The DCA curve showed that the nomogram model had good clinical net benefits when the threshold probability of the modeling group,internal verification group and external verification group were 0.03-0.82,0.02-0.78 and 0.06-0.88 respectively.Conclusion:The maximum tumor diameter,multiple lesions,preoperative lymph node metastasis,TNM staging stage Ⅲ-Ⅳ and levels of TG,T3,T4,FT3,FT4 and TSH are all risk factors for recurrence of thy-roid cancer after radical surgery via areola endoscopy,and the risk prediction visualization nomogram model con-structed based on this is helpful for clinical screening of high-risk patients to guide early intervention and reduce the risk of recurrence.

Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain fami-ly member ACSL5 and their effect on migration and in-vasion of breast cancer cell,and to explore the underly-ing mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were as-sessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentra-tions of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-α and p-AMPK-α were detected by Western blot.Results Leptin promoted breast cancer cell mi-gration and invasion and EMT.ACSL5 was significant-ly low expressed in breast cancer and related to progno-sis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.

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.

Family with sequence similarity 3 member A(FAM3A),a novel mitochondrial protein,plays a pivotal role in hepatic glucose and lipid metabolism by enhancing ATP synthesis and secretion and mod-ulating the ATP-P2 receptor-Akt signaling pathway.Dysregulation of FAM3A is closely associated with the pathogenesis of non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM).In this study,targeting FAM3A as a therapeutic candidate,we conducted virtual screening to identify 47 small-molecule compounds with potential binding activity.Surface plasmon resonance(SPR)analysis re-vealed three compounds exhibiting high binding affinity to FAM3 A.Further structural characterization of the FAM3A-compound complexes,combined with intermolecular interaction analysis,elucidated the binding mode of the lead compound Index 2(taxifolin)to FAM3A at atomic resolution.These findings provide critical insights into the molecular mechanisms underlying ligand-FAM3A interactions and deliver valuable chemical scaffolds for the development of therapeutics targeting NAFLD and T2DM.This work establishes a foundation for advancing drug discovery efforts focused on FAM3A-mediated metabolic disor-ders.

Objective:This study aimed to evaluate the application effect of opioid-free anesthesia(OFA)in modified radical mastectomy for breast cancer.Methods:80 patients undergoing unilateral modified radical mastec-tomy were randomly divided into two groups:general anesthesia group(G group)and OFA group(O group).The G group received general anesthesia with opioid drugs and a laryngeal mask,while the O group received general anes-thesia with intravenous lidocaine combined with thoracic paravertebral nerve block and a laryngeal mask.The average arterial pressure(MAP)and heart rate(HR)of the patients were recorded at the time of admission(T0),induction(T1),start of surgery(T2),gland resection(T3),and admission to the recovery room(T4).The surgical time,awakening time,ex-tubation time,and getting out of bed time were recorded.The VAS score at 2 hours(T5),6 hours(T6),and 12 hours(T7)after surgery,as well as the systemic immune-inflammatory index(SII)before surgery(T8),6 hours after surgery(T9),and 12 hours after surgery(T10)were recorded.The occurrence of postoperative nausea and vomiting(PONV)and post-mastectomy pain syndrome(PMPS)were recorded.The occurrence of adverse events such as poor nerve block effect,pneumothorax,hematoma,and local anesthetic toxicity were also recorded.Results:The MAP and HR of the O group were more stable than those of the G group during surgery(P＜0.05).The awakening time,extubation time,and getting out of bed time in the O group were earlier than those in the G group(P＜0.05).The VAS and SII values after surgery were significantly lower in the O group than in the G group(P＜0.05).The incidence of PONV was also signifi-cantly decreased(P＜0.05).In addition,no adverse events such as pneumothorax,hematoma,or local anesthetic toxic-ity occurred in the O group.Conclusion:Pioid-free anesthesia is safe and effective in modified radical mastectomy for breast cancer,shortening recovery time,time to first flatus,and time to ambulation,while alleviating postoperative pain,systemic inflammatory response,perioperative hemodynamic fluctuations,and the incidence of postoperative nau-sea and vomiting.

In October 2023, a patient with locally advanced breast cancer was treated in the Department of Reconstructive Microsurgery, Xuzhou Renci Hospital. Radical mastectomy for breast cancer was performed, and the huge soft tissue defect (40.0 cm×22.0 cm) was reconstructed by a pedicled transverse rectus abdominis myocutaneous flap (TRAMF) combined with a free deep inferior epigastric artery perforator flap (DIEPF) and a free anterolateral thigh perforator flap (ALTPF). The size of the lower abdominal flap was 28.0 cm×11.0 cm, and the size of ALTPF was 30.0 cm×11.0 cm. All flaps survived well with soft texture. Scores of Karnofsky Performance Status (KPS) and Visual Analogue Scale (VAS) were significantly improved at 1 month after the surgery. The patient refused chemotherapy, radiotherapy and other comprehensive treatments at the time. A local cancer recurrence in chest wall was found at 9 months after surgery, the patient was currently under chemotherapy and other comprehensive therapies.

In October 2023, a patient with locally advanced breast cancer was treated in the Department of Reconstructive Microsurgery, Xuzhou Renci Hospital. Radical mastectomy for breast cancer was performed, and the huge soft tissue defect (40.0 cm×22.0 cm) was reconstructed by a pedicled transverse rectus abdominis myocutaneous flap (TRAMF) combined with a free deep inferior epigastric artery perforator flap (DIEPF) and a free anterolateral thigh perforator flap (ALTPF). The size of the lower abdominal flap was 28.0 cm×11.0 cm, and the size of ALTPF was 30.0 cm×11.0 cm. All flaps survived well with soft texture. Scores of Karnofsky Performance Status (KPS) and Visual Analogue Scale (VAS) were significantly improved at 1 month after the surgery. The patient refused chemotherapy, radiotherapy and other comprehensive treatments at the time. A local cancer recurrence in chest wall was found at 9 months after surgery, the patient was currently under chemotherapy and other comprehensive therapies.

Objective:To explore the risk factors for recurrence of thyroid cancer after radical resection via areola endoscopy,and to construct a visual risk prediction model.Methods:The clinical data of 350 thyroid cancer patients who underwent radical surgery via areola endoscopy in our hospital from January 2016 to October 2018 were retro-spectively analyzed,and they were randomly divided into the modeling group(233 cases)and the internal validation group(117 cases)in a 2:1 ratio.All patients were followed up for 3 years after surgery,and the patients of modeling group were further divided into recurrent group(51)and non recurrent group(182)according to whether they with or not recurrence.Another 163 patients with thyroid cancer who underwent laparoscopic radical mastectomy at our hos-pital from January 2019 to May 2020 were selected as the external validation group.The risk factors for recurrence of thyroid cancer after radical surgery via areola endoscopy was analyzed by using Cox regression method,and a risk prediction nomogram model was established based on this.Internal validation of the nomogram model was conducted by using the Bootstrap method,and the calibration,predictive efficacy and clinical net benefit of the nomogram model were evaluated by the calibration curve,receiver operating characteristic(ROC)curve and decision curve analysis(DCA).The external validation group data was used for external validation.Results:The recurrence rate of thyroid cancer patients after 5 years of radical surgery via areola endoscopy was 21.64％(111/513).The proportions of multiple le-sions,preoperative lymph node metastasis,TNM stages Ⅲ-Ⅳ and maximum tumor diameter,the levels of thyro-globulin(TG),triiodothyronine(T3),thyroxine(T4),free triiodothyronine(FT3),free thyroxine(FT4)and thyroid stimulating hormone(TSH)in the recurrence group were higher than those in the non recurrence group(P<0.05).The Cox regres-sion analysis results showed that the maximum tumor diameter,multiple lesions,preoperative lymph node metasta-sis,TNM stage Ⅲ-Ⅳ and TG,T3,T4,FT3,FT4 and TSH levels were all risk factors for recurrence of thyroid cancer after radical surgery via areola endoscopy(P<0.05).The risk prediction nomogram model of recurrence of thyroid cancer af-ter radical surgery under areola endoscopy was constructed based on the above influencing factors.After internal and external validation,the consistency indices of the modeling group,internal verification group and external verification group were 0.832,0.825 and 0.41 respectively,and the calibration curves of three groups were close to the standard curve.The ROC curve analysis and verification showed that the area under the curve predicted by the nomogram model of the modeling group,internal verification group and external verification group were 0.859,0.847 and 0.853 respectively.The DCA curve showed that the nomogram model had good clinical net benefits when the threshold probability of the modeling group,internal verification group and external verification group were 0.03-0.82,0.02-0.78 and 0.06-0.88 respectively.Conclusion:The maximum tumor diameter,multiple lesions,preoperative lymph node metastasis,TNM staging stage Ⅲ-Ⅳ and levels of TG,T3,T4,FT3,FT4 and TSH are all risk factors for recurrence of thy-roid cancer after radical surgery via areola endoscopy,and the risk prediction visualization nomogram model con-structed based on this is helpful for clinical screening of high-risk patients to guide early intervention and reduce the risk of recurrence.