Background:Currently,there is a deficiency in a strong risk prediction framework for precisely evaluating the likelihood of severe postoperative complications in patients undergoing elective hepato-pancreatobiliary su...Background:Currently,there is a deficiency in a strong risk prediction framework for precisely evaluating the likelihood of severe postoperative complications in patients undergoing elective hepato-pancreatobiliary surgery subsequent to experiencing breakthrough infection of coronavirus disease 2019(COVID-19).This study aimed to find factors predicting postoperative complications and construct an innovative nomogram to pinpoint patients who were susceptible to developing severe complications following breakthrough infection of COVID-19 after undergoing elective hepato-pancreato-biliary surgery.Methods:This multicenter retrospective cohort study included consecutive patients who underwent elective hepato-pancreato-biliary surgeries between January 3 and April 1,2023 from four hospitals in China.All of these patients had experienced breakthrough infection of COVID-19 prior to their surgeries.Additionally,two groups of patients without preoperative COVID-19 infection were included as comparative controls.Surgical complications were meticulously documented and evaluated using the comprehensive complication index(CCI),which ranged from 0(uneventful course)to 100(death).A CCI value of 20.9 was identified as the threshold for defining severe complications.Results:Among 2636 patients who were included in this study,873 were included in the reference group I,941 in the reference group II,389 in the internal cohort,and 433 in the external validation cohort.Multivariate logistic regression analysis revealed that completing a full course of COVID-19 vaccination>6 months before surgery,undergoing surgery within 4 weeks of diagnosis of COVID-19 breakthrough infection,operation duration of 4 h or longer,cancer-related surgery,and major surgical procedures were significantly linked to a CCI>20.9.A nomogram model was constructed utilizing CCI>20.9 in the training cohort[area under the curve(AUC):0.919,95%confidence interval(CI):0.881–0.957],the internal validation cohort(AUC:0.910,95%CI:0.847–0.973),and the external validation cohort(AUC:0.841,95%CI:0.799–0.883).The calibration curve for the probability of CCI>20.9 demonstrated good agreement between the predictions made by the nomogram and the actual observations.Conclusions:The developed model holds significant potential in aiding clinicians with clinical decisionmaking and risk stratification for patients who have experienced breakthrough infection of COVID-19 prior to undergoing elective hepato-pancreato-biliary surgery.展开更多
BACKGROUND Acute kidney injury(AKI)after surgery appears to increase the risk of death in patients with liver cancer.In recent years,machine learning algorithms have been shown to offer higher discriminative efficienc...BACKGROUND Acute kidney injury(AKI)after surgery appears to increase the risk of death in patients with liver cancer.In recent years,machine learning algorithms have been shown to offer higher discriminative efficiency than classical statistical analysis.AIM To develop prediction models for AKI after liver cancer resection using machine learning techniques.METHODS We screened a total of 2450 patients who had undergone primary hepatocellular carcinoma resection at Changzheng Hospital,Shanghai City,China,from January 1,2015 to August 31,2020.The AKI definition used was consistent with the Kidney Disease:Improving Global Outcomes.We included in our analysis preoperative data such as demographic characteristics,laboratory findings,comorbidities,and medication,as well as perioperative data such as duration of surgery.Computerized algorithms used for model development included logistic regression(LR),support vector machine(SVM),random forest(RF),extreme gradient boosting(XGboost),and decision tree(DT).Feature importance was also ranked according to its contribution to model development.RESULTS AKI events occurred in 296 patients(12.1%)within 7 d after surgery.Among the original models based on machine learning techniques,the RF algorithm had optimal discrimination with an area under the curve value of 0.92,compared to 0.87 for XGBoost,0.90 for DT,0.90 for SVM,and 0.85 for LR.The RF algorithm also had the highest concordance-index(0.86)and the lowest Brier score(0.076).The variable that contributed the most in the RF algorithm was age,followed by cholesterol,and surgery time.CONCLUSION Machine learning algorithms are highly effective in discriminating patients at high risk of developing AKI.The successful application of machine learning models may help guide clinical decisions and help improve the long-term prognosis of patients.展开更多
To the Editor:WereadwithgreatinterestthearticlebyDr.Leeetal.[1],which compared the long-term outcomes of patients with perivascular hepatocellular carcinoma (HCC) after radiofrequency ablation(RFA) and surgical resect...To the Editor:WereadwithgreatinterestthearticlebyDr.Leeetal.[1],which compared the long-term outcomes of patients with perivascular hepatocellular carcinoma (HCC) after radiofrequency ablation(RFA) and surgical resection (SR) as first-line treatment. By using propensity score matching (PSM) analyses, the authors concluded that SR provided better long-term tumor control and overall survival than RFA for patients with small periportal tumors. Herein,展开更多
The application of tumor antigen-based immunotherapy is hindered by the rarity of validated immunogenic peptides.In this study,we aimed to investigate the potential of circular RNAs(circRNAs)as a novel source of tumor...The application of tumor antigen-based immunotherapy is hindered by the rarity of validated immunogenic peptides.In this study,we aimed to investigate the potential of circular RNAs(circRNAs)as a novel source of tumor antigen peptides in hepatobiliary tumor organoids.Using RNA-sequencing(RNA-seq)with an algorithm-based score tool,3950 translated tumor-specific circRNAs were predicted to generate 18971 antigen peptides in 27 organoids.In view of the antigen landscape,11 amino acid length(mer)peptides and human leukocyte antigen(HLA)-A binding peptides harbored the highest immunogenicity-related scores.In three out of five analyzed organoids,13 predicted antigen peptides were directly confirmed as HLA-A,-B,and-C(HLA-ABC)binding peptides with mass spectrometry(MS)-based immunopeptidomics.CircRNA-derived tumor-specific peptides presented by the HLA-ABC molecules stimulated cluster of differentiation 8(CD8)T cells to exhibit increased CD107a interferonγ(IFNγ)co-expressions and IFNγsecretion in flow cytometry and enzyme-linked immunosorbent assay(ELISA).Cytotoxic T cell activity targeting the organoids,induced by the immunogenic circRNA-derived peptides,was verified in a killing assay.Notably,the antigen peptide YGFNEILKK from circTBC1D15 was not only recognized as an HLA-ABC-presented peptide of the organoids but also drastically reduced the tumor organoid survival rate.Our findings highlight a crucial subset for generating tumor antigens,which has implications for targeting tumor-specific circRNAs in cancers.展开更多
BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatme...BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.展开更多
Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in re...Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.展开更多
BACKGROUND To investigate the preoperative factors influencing textbook outcomes(TO)in Intrahepatic cholangiocarcinoma(ICC)patients and evaluate the feasibility of an interpretable machine learning model for preoperat...BACKGROUND To investigate the preoperative factors influencing textbook outcomes(TO)in Intrahepatic cholangiocarcinoma(ICC)patients and evaluate the feasibility of an interpretable machine learning model for preoperative prediction of TO,we developed a machine learning model for preoperative prediction of TO and used the SHapley Additive exPlanations(SHAP)technique to illustrate the prediction process.AIM To analyze the factors influencing textbook outcomes before surgery and to establish interpretable machine learning models for preoperative prediction.METHODS A total of 376 patients diagnosed with ICC were retrospectively collected from four major medical institutions in China,covering the period from 2011 to 2017.Logistic regression analysis was conducted to identify preoperative variables associated with achieving TO.Based on these variables,an EXtreme Gradient Boosting(XGBoost)machine learning prediction model was constructed using the XGBoost package.The SHAP(package:Shapviz)algorithm was employed to visualize each variable's contribution to the model's predictions.Kaplan-Meier survival analysis was performed to compare the prognostic differences between the TO-achieving and non-TO-achieving groups.RESULTS Among 376 patients,287 were included in the training group and 89 in the validation group.Logistic regression identified the following preoperative variables influencing TO:Child-Pugh classification,Eastern Cooperative Oncology Group(ECOG)score,hepatitis B,and tumor size.The XGBoost prediction model demonstrated high accuracy in internal validation(AUC=0.8825)and external validation(AUC=0.8346).Survival analysis revealed that the disease-free survival rates for patients achieving TO at 1,2,and 3 years were 64.2%,56.8%,and 43.4%,respectively.CONCLUSION Child-Pugh classification,ECOG score,hepatitis B,and tumor size are preoperative predictors of TO.In both the training group and the validation group,the machine learning model had certain effectiveness in predicting TO before surgery.The SHAP algorithm provided intuitive visualization of the machine learning prediction process,enhancing its interpretability.展开更多
Background:Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma(HCC).Based on age,sex,alpha-fetoprote...Background:Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma(HCC).Based on age,sex,alpha-fetoprotein(AFP),and protein induced by vitamin K absence II(PIVKA-II)with/without AFP-L3,ASAP and GALAD models are potential diagnostic panels.The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases(CLDs).Methods:A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chi-nese hospitals.The etiologies of CLDs included hepatitis B virus(HBV),hepatitis C virus(HCV),alcoholic liver disease(ALD),and nonalcoholic fatty liver disease(NAFLD).Using area under the receiver operating characteristic curve(AUC)values,the diagnostic performances of ASAP and GALAD models were com-pared to detect HCC among patients with various etiologies of CLDs.Results:Among 248 HCC patients and 722 CLD controls,the ASAP model demonstrated the highest AUC(0.886)to detect HCC at any stage,outperforming the GALAD model(0.853,P=0.001),as well as any individual biomarker(0.687-0.799,all P<0.001).In the subgroup analysis of various CLDs etiologies,the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology.In addition,the ASAP model performed better in detecting early-stage(BCLC stage 0/A)HCC versus the GALAD model.Conclusions:Despite using one less laboratory variable(AFP-L3),the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various eti-ologies of CLDs-related HCC.展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantati...Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.展开更多
BACKGROUND Most patients with non-alcoholic fatty liver disease(NAFLD)exhibit mild symptoms;however,without timely intervention,the condition may progress to cirrhosis or even liver cancer.The development of internet-...BACKGROUND Most patients with non-alcoholic fatty liver disease(NAFLD)exhibit mild symptoms;however,without timely intervention,the condition may progress to cirrhosis or even liver cancer.The development of internet-based proactive follow-up management models has provided new avenues for medical services,allowing patients to access online consultations and enabling doctors to efficiently manage patient information.These models have particular significance for NAFLD patients,as they can enhance compliance and facilitate timely intervention.AIM To explore the effect of an internet-based proactive follow-up management model on the prognosis management of patients with NAFLD.METHODS This study collected data from 145 patients diagnosed with NAFLD.The patients were randomly divided into the internet-based proactive follow-up group(71 patients)and the traditional follow-up group(74 patients).The traditional followup group underwent routine outpatient and telephone follow-up,while the internet-based proactive follow-up group used the WeChat applet for active reminding,health education and follow-up.During the follow-up period,patients’compliance,disease control status,and quality of life score were recorded.RESULTS The follow-up compliance of patients in the internet-based proactive follow-up group was significantly higher than that in the traditional follow-up group(85.6%vs 68.4%,P<0.01),and the quality of life score was significantly improved(78.9±7.6 vs 72.5±8.4,P<0.01).CONCLUSION The internet-based proactive follow-up management model can provide personalized health management plans and reduce the risk of disease deterioration,making it worthy of promotion in a broader healthcare context.展开更多
BACKGROUND The frequent occurrence of respiratory diseases in the island reef environment of the navy severely affects the health of personnel and the combat effectiveness of the troops.Current common screening method...BACKGROUND The frequent occurrence of respiratory diseases in the island reef environment of the navy severely affects the health of personnel and the combat effectiveness of the troops.Current common screening methods can only indicate whether there is an infection with pathogenic microorganisms but not the degree of disease progression.Therefore,it is necessary to identify simple-to-operate and cost-effective methods that indicate the degree of disease progression,based on traditional screening methods.AIM To explores correlation between serum concentrations of nicotinamide phosphoribosyltransferase(NAMPT),nicotinamide nucleotide adenylyltransferase 1(NMNAT1),and the risk of upper respiratory infections in the island reef envirsonment.METHODS A total of 600 cases of upper respiratory infections among naval officers and soldiers were included.Types of infection were confirmed through sputum culture combined with multiplex polymerase chain reaction.The serum concentrations of NAMPT and NMNAT1 were measured using ELISA,and infection severity was assessed using the pneumonia severity index(PSI).Statistical analysis was performed using nonparametric tests and Spearman correlation analysis.RESULTS The serum concentrations of NAMPT and NMNAT1 in high-risk group patients with PSI were significantly lower than those in the medium and low-risk groups(P<0.05),and the concentrations increased in a stepwise manner with disease progression.However,within the same risk group,the differences in concentrations of NAMPT and NMNAT1among patients infected with different pathogens were not significant(P>0.05).CONCLUSIONConcentrations of NAMPT and NMNAT1 are closely related to severity of upper respiratory infections,and theircommon regulatory mechanisms provide new directions for development of broad-spectrum anti-infectionstrategies.展开更多
BACKGROUND Core-fucosylated low-molecular-weight kininogen(LMWK-Fc)levels are significantly elevated in patients with liver fibrosis and cirrhosis.AIM To assess the value of LMWK-Fc as a diagnostic biomarker for liver...BACKGROUND Core-fucosylated low-molecular-weight kininogen(LMWK-Fc)levels are significantly elevated in patients with liver fibrosis and cirrhosis.AIM To assess the value of LMWK-Fc as a diagnostic biomarker for liver fibrosis.METHODS Our study included 132 healthy people and 132 patients with liver fibrosis.The LMWK-Fc level was measured based on the principle of chemiluminescence.Fibrosis stage and inflammatory activity were assessed by liver biopsy.Comparative analysis between groups and receiver operating characteristic curve analysis were performed.RESULTS LMWK-Fc had an area under the curve of 0.871,which indicates a good level of performance in distinguishing between patients with and without fibrosis.Furthermore,the LMWK-Fc level had a certain correlation with the liver stiffness value,which reached 0.5789.CONCLUSION LMWK-Fc could be used as a non-invasive marker of liver fibrosis.Further studies are needed to evaluate the usefulness of this marker.展开更多
BACKGROUND Patients with chronic hepatitis B(CHB)require long-term antiviral therapy.The effects of different antiviral drugs on kidney function are unclear.There is a lack of effective markers for monitoring early re...BACKGROUND Patients with chronic hepatitis B(CHB)require long-term antiviral therapy.The effects of different antiviral drugs on kidney function are unclear.There is a lack of effective markers for monitoring early renal impairment.AIM To investigate the rate of abnormal renal function index and related potential hazards in patients with CHB.METHODS Clinical data of patients with CHB with urinaryβ2-microglobulin(β2-M)detec-tion,including demographic characteristics,hepatitis B virus(HBV)DNA,serum liver function(alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin),serum renal function(urea nitrogen,creatinine),blood lipid index(high density lipoprotein,low density lipoprotein,cholesterol,trigly-ceride),liver imaging,and other routine tests were retrospectively collected.The normal level of urinaryβ2-M and estimated glomerular filtration rate(eGFR)is defined as<0.173 mg/L and≥90 mL/min/1.73 m^(2),retrospectively.The pro-portion of patients with abnormal renal function index and related risk factors were analyzed.RESULTS A total of 500 patients with CHB were enrolled;these patients were aged 44.7±10.8 years,67.2%(336/500)were male,57.2%(286/500)were treated with anti-viral drugs,and 52.2%(261/500)had an HBV-related family history.In total,28.8%(144/500)of patients had fatty liver,35.0%(175/500)had liver fibrosis,and 13.2%(66/500)had cirrhosis.The proportion of patients with eGFR<90 mL/min/1.73 m^(2) was 43.2%(216/500),and the abnormal rate of urinaryβ2-M was 56.2%(281/500).There was no significant difference in the abnormal rate of urinaryβ2-M between the untreated group and the antiviral treated group(54.2%vs 57.7%;P=0.25).The abnormal rate ofβ2-M after long-term entecavir treatment(more than 1 year)was 54.6%(89/163).In the treatment group,56.4%(92/163)of patients with eGFR≥90 mL/min/1.73 m^(2) had abnormal urinaryβ2-M.CONCLUSION In patients with CHB,a higher proportion had greater urinaryβ2-M levels than eGFR for renal injury.Male patients should pay more attention to renal function and use antiviral regimens with a renal safety profile.展开更多
Background:Hepatocellular carcinoma(HCC)is a prevalent liver malignancy.This study examined the roles of transforming growth factor beta(TGF-β)and cytochrome b5 domain containing 2(CYB5D2)in HCC etiology and their pr...Background:Hepatocellular carcinoma(HCC)is a prevalent liver malignancy.This study examined the roles of transforming growth factor beta(TGF-β)and cytochrome b5 domain containing 2(CYB5D2)in HCC etiology and their prognostic biomarker potential.Methods:Key modules and prognostic genes were identified by analyzing the GSE101685 dataset by weighted gene co-expression network analysis(WGCNA)and Least absolute shrinkage and selection operator(LASSO)Cox regression.The expression levels of CYB5D2 and TGF-βin HCC cell lines were quantified using Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blotting(WB)assays.Effects of CYB5D2 overexpression on cell proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)marker regulation were assessed in vitro,while in vivo tumorigenicity was evaluated using a xenograft model of HCC in nude mice.Results:In this study,WGCNA identified the turquoise module as significantly associated with HCC,containing 452 DEGs.LASSO Cox regression analysis revealed 9 key prognostic genes,with CYB5D2 being underexpressed in HCC cells and tissues.TGF-βwas negatively correlated with CYB5D2 expression,resulting in poor patient prognosis.Functional assays demonstrated that CYB5D2 overexpression inhibited proliferation,migration,and invasion of HCC cell lines,and altered EMT marker expression.Furthermore,the addition of TGF-βpartially reversed the suppressive effects caused by CYB5D2 overexpression.In vivo,CYB5D2 overexpression significantly reduced tumor growth,indicating its potential as a therapeutic target for HCC.Conclusion:The tumor suppressor function of CYB5D2 in HCC and its interaction with TGF-βoffered fresh information on the molecular pathophysiology of HCC and possible treatment avenues.展开更多
As one of the most prevalent malignant tumors,hepatocellular carcinoma(HCC)represents a major global public health burden.Traditionally,HCC pathogenesis has been attributed to chronic liver diseases(viral hepatitis,ci...As one of the most prevalent malignant tumors,hepatocellular carcinoma(HCC)represents a major global public health burden.Traditionally,HCC pathogenesis has been attributed to chronic liver diseases(viral hepatitis,cirrhosis)and aflatoxin exposure.However,with evolving lifestyles and environmental changes,sleep disorders have become increasingly prevalent.Emerging evidence suggest that sleep disorders may contribute to hepatocarcinogenesis through multiple mechanisms,including immunity environment disorder,oxidative stress,metabolic dysregulation,disruption of gut microbiota,and circadian rhythm disruption,thereby influencing disease progression and patient prognosis.This review summarizes epidemiological evidence on the relationship between sleep disorders and HCC incidence,explores the underlying mechanisms through which sleep disorders contribute to HCC,and discusses clinical challenges and potential intervention strategies.Our objective is to provide novel insights into HCC prevention and therapeutic approaches.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide and currently lacks effective treatment options.This is particularly true for advanced HCC,for which conventional therapies...BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide and currently lacks effective treatment options.This is particularly true for advanced HCC,for which conventional therapies often lead to a poor prognosis.AIM To assess the safety and efficacy of transarterial chemoembolization(TACE)with donafenib and immune checkpoint inhibitors(ICIs)for unresectable HCC.METHODS We retrospectively assessed the data of patients with HCC who underwent TACE combined with donafenib and an ICI(tislelizumab or cedilimumab).Patients received oral donafenib daily for 2 weeks before TACE,followed by tislelizumab or cedilimumab 200 mg intravenously on day 1 of a 21-day therapeutic cycle.The primary endpoints were objective response rate,disease control rate,and duration of response according to the modified RECIST criteria.The secondary endpoint was presence of treatment-related adverse events(TRAEs).RESULTS The median follow-up was 7.8 months(95%CI:5.0-11.8 months).The objective response rate was 60.0%(18/30),while the disease control rate was 93.3%.The median duration of response in confirmed responders was 6.6 months(95%CI:1.3-12.9 months).The median progression-free survival was 11.8 months(95%CI:8.3-15.4 months).More than half of the patients survived until the end of the study.Grade>3 TRAEs occurred in 40%of the patients with no grade 5 TRAEs reported.The most common grade 3/4 TRAE was palmar-plantar erythrodysesthesia,a dermatologic condition characterized by painful redness and swelling of the palms and soles,with an incidence of 56.7%.No ICI-related adverse effects were observed.CONCLUSION TACE combined with donafenib and ICI is a promising and safe therapeutic regimen for unresectable HCC.展开更多
BACKGROUND The clinical effectiveness of magnetically controlled capsule endoscopy(MCE)is well established.However,problems,such as abdominal distension,insufficient gastric filling,and prolonged gastric retention tim...BACKGROUND The clinical effectiveness of magnetically controlled capsule endoscopy(MCE)is well established.However,problems,such as abdominal distension,insufficient gastric filling,and prolonged gastric retention time,persist with MCE gastric preparations.AIM To compare gastric filling using a carbonated soft drink with that using pure water during MCE.METHODS We performed an open-label randomised controlled trial at the Endoscopy Centre of Changhai Hospital in Shanghai.Patients aged 18-80 years,with or without gastrointestinal symptoms,scheduled for MCE were consecutively recruited.Those who provided informed consent were randomly assigned to the carbonated soft drink group(C group)or water group(W group)in a 1:1 ratio.For patients in the W group,1000 mL of water was ingested to distend the stomach,whereas for patients in the C group,550 mL of carbonated soft drink was provided,and patients were required to drink quickly while minimising burping.The primary endpoint was the number of patients with a gastric filling score of≥4 within 5 minutes after the capsule entered the stomach.RESULTS From December 3,2020 to May 17,2021,252 patients(141 men),aged 18-77 years,were assigned to the C(n=126)and W(n=126)groups.For the primary outcome,123 patients in the C group achieved a gastric filling score of≥4(97.62%vs 80.16%,P<0.0001).More patients in the C group had the highest gastric filling scores within the first 5 min(78.57%vs 29.37%,P<0.0001)and 10 minutes(54.76%vs 13.49%,P<0.0001)after the capsule entered the stomach.More patients in the W group required extra liquid for gastric refilling(1.59%vs 16.67%,P<0.0001).Transpyloric passage of the capsule under magnetic control was successfully performed in 43 patients in the C group(P<0.0001),accompanied by a shorter gastric transit time(53.27±53.83 minutes vs 71.12±52.19 minutes,P=0.001).CONCLUSION Carbonated soft drinks demonstrated superior and more sustained gastric filling compared with those of water alone,with the potential to promote gastric emptying.展开更多
Background:Despite advances in surgical treatment,high recurrence after surgery remains a challenge for patients with hepatocellular carcinoma(HCC).This study aimed to investigate the association between compliance to...Background:Despite advances in surgical treatment,high recurrence after surgery remains a challenge for patients with hepatocellular carcinoma(HCC).This study aimed to investigate the association between compliance to regular follow-up and long-term oncological outcomes among patients undergoing curative resection for HCC.Methods:This multicenter study included patients who underwent curative resection for early-stage HCC between January 2012 and December 2021 at 12 liver surgery centers.Patients were stratified into a regular follow-up group(follow-up every 2–3 months for the first 2 years and every 3–6 months thereafter)and an irregular/no follow-up group.Overall survival(OS),time to recurrence(TTR),and post-recurrence survival(PRS)were compared between the two groups.Results:Among 1544 patients,786(50.9%)underwent regular follow-up during postoperative follow-up.The regular follow-up group had better OS(median:113.4 vs.94.5 months,P=0.010)and PRS(median:37.9 vs.16.3 months,P<0.001)than the irregular/no follow-up group,although TTR was comparable(median:61.4 vs.66.2 months,P=0.161).Furthermore,patients in the regular follow-up group had a lower incidence of tumor beyond the Milan criteria at recurrence(41.6%vs.50.4%,P=0.013)and were more likely to receive curative treatments for recurrence(56.1%vs.49.3%,P=0.061).On multivariate analysis,compliance to regular follow-up was an independent factor associated with better OS[hazard ratio(HR)=0.777,95%confidence interval(CI):0.663–0.910,P=0.002]and PRS(HR=0.523,95%CI:0.428–0.638,P<0.001).Conclusions:Compliance to regular follow-up improved OS and PRS after curative resection for HCC,highlighting the importance of postoperative regular follow-up for early detection of recurrence and timely intervention.展开更多
AIM:To investigate the indications for lymph node dissection(LND)in intrahepatic cholangiocarcinoma patients.METHODS:A retrospective analysis was conducted on 124 intrahepatic cholangiocarcinoma(ICC)patients who had u...AIM:To investigate the indications for lymph node dissection(LND)in intrahepatic cholangiocarcinoma patients.METHODS:A retrospective analysis was conducted on 124 intrahepatic cholangiocarcinoma(ICC)patients who had undergone surgical resection of ICC from January 2006 to December 2007.Curative resection was attempted for all patients unless there were metastases to lymph nodes(LNs)beyond the hepatoduodenal ligament.Prophylactic LND was performed in patients in whom any enlarged LNs had been suspicious for metastases.The patients were classified according to the LND and LN metastases.Clinicopathologic,operative,and long-term survival data were collected retrospectively.The impact on survival of LND during primary resection was analyzed.RESULTS:Of 53 patients who had undergone hepatic resection with curative intent combined with regional LND,11 had lymph nodes metastases.Whether or not patients without lymph node involvement had undergone LND made no significant difference to their survival(P=0.822).Five patients with multiple tumors and involvement of lymph nodes underwent hepatic resection with LND;their survival curve did not differ significantly from that of the palliative resection group(P=0.744).However,there were significant differences in survival between patients with lymph node involvement and a solitary tumor who underwent hepatic resection with LND and the palliative resection group(median survival time 12 mo vs 6.0 mo,P=0.013).CONCLUSION:ICC patients without lymph node involvement and patients with multiple tumors and lymph node metastases may not benefit from aggressive lymphadenectomy.Routine LND should be considered with discretion.展开更多
AIM To clone and identify the whole cDNA ofMXR7 gene and to find out its expression inhuman HCC,and normal tissues.METHODS The DNA primers were designed andsynthesized according to the whole cDNAsequence of MXR? gene....AIM To clone and identify the whole cDNA ofMXR7 gene and to find out its expression inhuman HCC,and normal tissues.METHODS The DNA primers were designed andsynthesized according to the whole cDNAsequence of MXR? gene.The cDNA of humanHCC was taken as the template while the cDNA ofMXR7 gene was synthesized by polymerasechain reaction（PCR）.Recombinant DNAconforming to reading frame was constructed byconnecting purified PCR product of the cDNA ofMXR? gene with expression vector pGEX-5X-1 offusion protein.The plasmid MXRT/pGEX-5X-1was identified by sequencing.Using <sup>32</sup>p labeledMXR? cDNA as probe,MXR7 mRNA expressionwas detected by Northern blot analysis in 12different human normal tissues,7 preoperativelyuntreated non-liver tumor tissues,30preoperatively untreated HCC,theparacancerous liver tissues and 12 normal livertissues samples.RESULTS Restriction enzyme and sequenceanalysis confirmed that the insertion sequence invector pGEX-5X-1 was the same as the cDNAsequence of MXR7 gene.Northern blot analysisshowed no expression of MXR? mRNA in 12 kindsof normal human tissues including liver,7 tumortissues in other sites and 12 normal livertissues,the frequencies of MXR7 mRNA expression in HCC and paracancerous livertissues were 76.6% and 13.3%,respectively.The frequency of MXR7 mRNA expression in HCCwithout elevation of serum AFP and in HCC【5cm was 90%（9/10）and 83.3%（5/6）,respectively.CONCLUSION MXR7 mRNA is highly expressedin human HCC,which is specific and occurs at anearly stage of HCC,suggesting MXR7 mRNA canbe a tumor biomarker for HCC.The detection ofMXR7 mRNA expression in the biopsied livertissue is helpful in discovering early subclinicalliver cancer in those with negative serum AFP.展开更多
基金supported by grants from the Science Fund for Creative Research Groups of the National Natural Science Founda-tion of China(81521091 and 82073031)the National Natural Sci-ence Foundation of China(92269204)Clinical Research Plan of SHDC(SHDC2020CR5007 and SHDC22020213)。
文摘Background:Currently,there is a deficiency in a strong risk prediction framework for precisely evaluating the likelihood of severe postoperative complications in patients undergoing elective hepato-pancreatobiliary surgery subsequent to experiencing breakthrough infection of coronavirus disease 2019(COVID-19).This study aimed to find factors predicting postoperative complications and construct an innovative nomogram to pinpoint patients who were susceptible to developing severe complications following breakthrough infection of COVID-19 after undergoing elective hepato-pancreato-biliary surgery.Methods:This multicenter retrospective cohort study included consecutive patients who underwent elective hepato-pancreato-biliary surgeries between January 3 and April 1,2023 from four hospitals in China.All of these patients had experienced breakthrough infection of COVID-19 prior to their surgeries.Additionally,two groups of patients without preoperative COVID-19 infection were included as comparative controls.Surgical complications were meticulously documented and evaluated using the comprehensive complication index(CCI),which ranged from 0(uneventful course)to 100(death).A CCI value of 20.9 was identified as the threshold for defining severe complications.Results:Among 2636 patients who were included in this study,873 were included in the reference group I,941 in the reference group II,389 in the internal cohort,and 433 in the external validation cohort.Multivariate logistic regression analysis revealed that completing a full course of COVID-19 vaccination>6 months before surgery,undergoing surgery within 4 weeks of diagnosis of COVID-19 breakthrough infection,operation duration of 4 h or longer,cancer-related surgery,and major surgical procedures were significantly linked to a CCI>20.9.A nomogram model was constructed utilizing CCI>20.9 in the training cohort[area under the curve(AUC):0.919,95%confidence interval(CI):0.881–0.957],the internal validation cohort(AUC:0.910,95%CI:0.847–0.973),and the external validation cohort(AUC:0.841,95%CI:0.799–0.883).The calibration curve for the probability of CCI>20.9 demonstrated good agreement between the predictions made by the nomogram and the actual observations.Conclusions:The developed model holds significant potential in aiding clinicians with clinical decisionmaking and risk stratification for patients who have experienced breakthrough infection of COVID-19 prior to undergoing elective hepato-pancreato-biliary surgery.
文摘BACKGROUND Acute kidney injury(AKI)after surgery appears to increase the risk of death in patients with liver cancer.In recent years,machine learning algorithms have been shown to offer higher discriminative efficiency than classical statistical analysis.AIM To develop prediction models for AKI after liver cancer resection using machine learning techniques.METHODS We screened a total of 2450 patients who had undergone primary hepatocellular carcinoma resection at Changzheng Hospital,Shanghai City,China,from January 1,2015 to August 31,2020.The AKI definition used was consistent with the Kidney Disease:Improving Global Outcomes.We included in our analysis preoperative data such as demographic characteristics,laboratory findings,comorbidities,and medication,as well as perioperative data such as duration of surgery.Computerized algorithms used for model development included logistic regression(LR),support vector machine(SVM),random forest(RF),extreme gradient boosting(XGboost),and decision tree(DT).Feature importance was also ranked according to its contribution to model development.RESULTS AKI events occurred in 296 patients(12.1%)within 7 d after surgery.Among the original models based on machine learning techniques,the RF algorithm had optimal discrimination with an area under the curve value of 0.92,compared to 0.87 for XGBoost,0.90 for DT,0.90 for SVM,and 0.85 for LR.The RF algorithm also had the highest concordance-index(0.86)and the lowest Brier score(0.076).The variable that contributed the most in the RF algorithm was age,followed by cholesterol,and surgery time.CONCLUSION Machine learning algorithms are highly effective in discriminating patients at high risk of developing AKI.The successful application of machine learning models may help guide clinical decisions and help improve the long-term prognosis of patients.
文摘To the Editor:WereadwithgreatinterestthearticlebyDr.Leeetal.[1],which compared the long-term outcomes of patients with perivascular hepatocellular carcinoma (HCC) after radiofrequency ablation(RFA) and surgical resection (SR) as first-line treatment. By using propensity score matching (PSM) analyses, the authors concluded that SR provided better long-term tumor control and overall survival than RFA for patients with small periportal tumors. Herein,
基金the National Natural Science Foundation of China(U21A20376,82102871,81988101,81903184,81790633,and 81830054)the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-07E00065)+1 种基金the National Science Foundation of Shanghai(21XD1404600,21JC1406600,and 22140901000)the China Postdoctoral Science Foundation(2020M671007).
文摘The application of tumor antigen-based immunotherapy is hindered by the rarity of validated immunogenic peptides.In this study,we aimed to investigate the potential of circular RNAs(circRNAs)as a novel source of tumor antigen peptides in hepatobiliary tumor organoids.Using RNA-sequencing(RNA-seq)with an algorithm-based score tool,3950 translated tumor-specific circRNAs were predicted to generate 18971 antigen peptides in 27 organoids.In view of the antigen landscape,11 amino acid length(mer)peptides and human leukocyte antigen(HLA)-A binding peptides harbored the highest immunogenicity-related scores.In three out of five analyzed organoids,13 predicted antigen peptides were directly confirmed as HLA-A,-B,and-C(HLA-ABC)binding peptides with mass spectrometry(MS)-based immunopeptidomics.CircRNA-derived tumor-specific peptides presented by the HLA-ABC molecules stimulated cluster of differentiation 8(CD8)T cells to exhibit increased CD107a interferonγ(IFNγ)co-expressions and IFNγsecretion in flow cytometry and enzyme-linked immunosorbent assay(ELISA).Cytotoxic T cell activity targeting the organoids,induced by the immunogenic circRNA-derived peptides,was verified in a killing assay.Notably,the antigen peptide YGFNEILKK from circTBC1D15 was not only recognized as an HLA-ABC-presented peptide of the organoids but also drastically reduced the tumor organoid survival rate.Our findings highlight a crucial subset for generating tumor antigens,which has implications for targeting tumor-specific circRNAs in cancers.
基金Shanghai Pudong New Area Health Commission’s Excellent Young Medical Talent Training Plan,No.PWRq2020-68Shanghai Pudong New Area Health Commission Discipline Leader Training Project,No.PWRd2020-16Shanghai Pudong New Area Science and Technology Development Fund,No.PKJ2020-Y36.
文摘BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.
基金supported by the National Natural Science Foun-dation of China(Grant Nos.:32170680 and T2122018)the Natural Science Foundation of Shanghai,China(Grant No.:21ZR1476000)the CAS Youth Innovation Promotion Association,China(Grant No.:Y2022076).
文摘Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.
基金Supported by National Key Research and Development Program,No.2022YFC2407304Major Research Project for Middle-Aged and Young Scientists of Fujian Provincial Health Commission,No.2021ZQNZD013+2 种基金The National Natural Science Foundation of China,No.62275050Fujian Province Science and Technology Innovation Joint Fund Project,No.2019Y9108Major Science and Technology Projects of Fujian Province,No.2021YZ036017.
文摘BACKGROUND To investigate the preoperative factors influencing textbook outcomes(TO)in Intrahepatic cholangiocarcinoma(ICC)patients and evaluate the feasibility of an interpretable machine learning model for preoperative prediction of TO,we developed a machine learning model for preoperative prediction of TO and used the SHapley Additive exPlanations(SHAP)technique to illustrate the prediction process.AIM To analyze the factors influencing textbook outcomes before surgery and to establish interpretable machine learning models for preoperative prediction.METHODS A total of 376 patients diagnosed with ICC were retrospectively collected from four major medical institutions in China,covering the period from 2011 to 2017.Logistic regression analysis was conducted to identify preoperative variables associated with achieving TO.Based on these variables,an EXtreme Gradient Boosting(XGBoost)machine learning prediction model was constructed using the XGBoost package.The SHAP(package:Shapviz)algorithm was employed to visualize each variable's contribution to the model's predictions.Kaplan-Meier survival analysis was performed to compare the prognostic differences between the TO-achieving and non-TO-achieving groups.RESULTS Among 376 patients,287 were included in the training group and 89 in the validation group.Logistic regression identified the following preoperative variables influencing TO:Child-Pugh classification,Eastern Cooperative Oncology Group(ECOG)score,hepatitis B,and tumor size.The XGBoost prediction model demonstrated high accuracy in internal validation(AUC=0.8825)and external validation(AUC=0.8346).Survival analysis revealed that the disease-free survival rates for patients achieving TO at 1,2,and 3 years were 64.2%,56.8%,and 43.4%,respectively.CONCLUSION Child-Pugh classification,ECOG score,hepatitis B,and tumor size are preoperative predictors of TO.In both the training group and the validation group,the machine learning model had certain effectiveness in predicting TO before surgery.The SHAP algorithm provided intuitive visualization of the machine learning prediction process,enhancing its interpretability.
基金supported by grants from the National Natural Science Foundation of China(81972726 and 82273074)Abbott Diagnostics(ADD-China-2016).
文摘Background:Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma(HCC).Based on age,sex,alpha-fetoprotein(AFP),and protein induced by vitamin K absence II(PIVKA-II)with/without AFP-L3,ASAP and GALAD models are potential diagnostic panels.The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases(CLDs).Methods:A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chi-nese hospitals.The etiologies of CLDs included hepatitis B virus(HBV),hepatitis C virus(HCV),alcoholic liver disease(ALD),and nonalcoholic fatty liver disease(NAFLD).Using area under the receiver operating characteristic curve(AUC)values,the diagnostic performances of ASAP and GALAD models were com-pared to detect HCC among patients with various etiologies of CLDs.Results:Among 248 HCC patients and 722 CLD controls,the ASAP model demonstrated the highest AUC(0.886)to detect HCC at any stage,outperforming the GALAD model(0.853,P=0.001),as well as any individual biomarker(0.687-0.799,all P<0.001).In the subgroup analysis of various CLDs etiologies,the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology.In addition,the ASAP model performed better in detecting early-stage(BCLC stage 0/A)HCC versus the GALAD model.Conclusions:Despite using one less laboratory variable(AFP-L3),the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various eti-ologies of CLDs-related HCC.
基金Supported by the National Natural Science Foundation of China,No.82270634Third Affiliated Hospital of Naval Medical University,No.tf2024yzyy01.
文摘Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.
文摘BACKGROUND Most patients with non-alcoholic fatty liver disease(NAFLD)exhibit mild symptoms;however,without timely intervention,the condition may progress to cirrhosis or even liver cancer.The development of internet-based proactive follow-up management models has provided new avenues for medical services,allowing patients to access online consultations and enabling doctors to efficiently manage patient information.These models have particular significance for NAFLD patients,as they can enhance compliance and facilitate timely intervention.AIM To explore the effect of an internet-based proactive follow-up management model on the prognosis management of patients with NAFLD.METHODS This study collected data from 145 patients diagnosed with NAFLD.The patients were randomly divided into the internet-based proactive follow-up group(71 patients)and the traditional follow-up group(74 patients).The traditional followup group underwent routine outpatient and telephone follow-up,while the internet-based proactive follow-up group used the WeChat applet for active reminding,health education and follow-up.During the follow-up period,patients’compliance,disease control status,and quality of life score were recorded.RESULTS The follow-up compliance of patients in the internet-based proactive follow-up group was significantly higher than that in the traditional follow-up group(85.6%vs 68.4%,P<0.01),and the quality of life score was significantly improved(78.9±7.6 vs 72.5±8.4,P<0.01).CONCLUSION The internet-based proactive follow-up management model can provide personalized health management plans and reduce the risk of disease deterioration,making it worthy of promotion in a broader healthcare context.
文摘BACKGROUND The frequent occurrence of respiratory diseases in the island reef environment of the navy severely affects the health of personnel and the combat effectiveness of the troops.Current common screening methods can only indicate whether there is an infection with pathogenic microorganisms but not the degree of disease progression.Therefore,it is necessary to identify simple-to-operate and cost-effective methods that indicate the degree of disease progression,based on traditional screening methods.AIM To explores correlation between serum concentrations of nicotinamide phosphoribosyltransferase(NAMPT),nicotinamide nucleotide adenylyltransferase 1(NMNAT1),and the risk of upper respiratory infections in the island reef envirsonment.METHODS A total of 600 cases of upper respiratory infections among naval officers and soldiers were included.Types of infection were confirmed through sputum culture combined with multiplex polymerase chain reaction.The serum concentrations of NAMPT and NMNAT1 were measured using ELISA,and infection severity was assessed using the pneumonia severity index(PSI).Statistical analysis was performed using nonparametric tests and Spearman correlation analysis.RESULTS The serum concentrations of NAMPT and NMNAT1 in high-risk group patients with PSI were significantly lower than those in the medium and low-risk groups(P<0.05),and the concentrations increased in a stepwise manner with disease progression.However,within the same risk group,the differences in concentrations of NAMPT and NMNAT1among patients infected with different pathogens were not significant(P>0.05).CONCLUSIONConcentrations of NAMPT and NMNAT1 are closely related to severity of upper respiratory infections,and theircommon regulatory mechanisms provide new directions for development of broad-spectrum anti-infectionstrategies.
文摘BACKGROUND Core-fucosylated low-molecular-weight kininogen(LMWK-Fc)levels are significantly elevated in patients with liver fibrosis and cirrhosis.AIM To assess the value of LMWK-Fc as a diagnostic biomarker for liver fibrosis.METHODS Our study included 132 healthy people and 132 patients with liver fibrosis.The LMWK-Fc level was measured based on the principle of chemiluminescence.Fibrosis stage and inflammatory activity were assessed by liver biopsy.Comparative analysis between groups and receiver operating characteristic curve analysis were performed.RESULTS LMWK-Fc had an area under the curve of 0.871,which indicates a good level of performance in distinguishing between patients with and without fibrosis.Furthermore,the LMWK-Fc level had a certain correlation with the liver stiffness value,which reached 0.5789.CONCLUSION LMWK-Fc could be used as a non-invasive marker of liver fibrosis.Further studies are needed to evaluate the usefulness of this marker.
文摘BACKGROUND Patients with chronic hepatitis B(CHB)require long-term antiviral therapy.The effects of different antiviral drugs on kidney function are unclear.There is a lack of effective markers for monitoring early renal impairment.AIM To investigate the rate of abnormal renal function index and related potential hazards in patients with CHB.METHODS Clinical data of patients with CHB with urinaryβ2-microglobulin(β2-M)detec-tion,including demographic characteristics,hepatitis B virus(HBV)DNA,serum liver function(alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin),serum renal function(urea nitrogen,creatinine),blood lipid index(high density lipoprotein,low density lipoprotein,cholesterol,trigly-ceride),liver imaging,and other routine tests were retrospectively collected.The normal level of urinaryβ2-M and estimated glomerular filtration rate(eGFR)is defined as<0.173 mg/L and≥90 mL/min/1.73 m^(2),retrospectively.The pro-portion of patients with abnormal renal function index and related risk factors were analyzed.RESULTS A total of 500 patients with CHB were enrolled;these patients were aged 44.7±10.8 years,67.2%(336/500)were male,57.2%(286/500)were treated with anti-viral drugs,and 52.2%(261/500)had an HBV-related family history.In total,28.8%(144/500)of patients had fatty liver,35.0%(175/500)had liver fibrosis,and 13.2%(66/500)had cirrhosis.The proportion of patients with eGFR<90 mL/min/1.73 m^(2) was 43.2%(216/500),and the abnormal rate of urinaryβ2-M was 56.2%(281/500).There was no significant difference in the abnormal rate of urinaryβ2-M between the untreated group and the antiviral treated group(54.2%vs 57.7%;P=0.25).The abnormal rate ofβ2-M after long-term entecavir treatment(more than 1 year)was 54.6%(89/163).In the treatment group,56.4%(92/163)of patients with eGFR≥90 mL/min/1.73 m^(2) had abnormal urinaryβ2-M.CONCLUSION In patients with CHB,a higher proportion had greater urinaryβ2-M levels than eGFR for renal injury.Male patients should pay more attention to renal function and use antiviral regimens with a renal safety profile.
基金National Natural Science Foundation of China Youth Training Project(2021GZR003)Medical-Engineering Interdisciplinary Research Youth Training Project(2022YGJC001).
文摘Background:Hepatocellular carcinoma(HCC)is a prevalent liver malignancy.This study examined the roles of transforming growth factor beta(TGF-β)and cytochrome b5 domain containing 2(CYB5D2)in HCC etiology and their prognostic biomarker potential.Methods:Key modules and prognostic genes were identified by analyzing the GSE101685 dataset by weighted gene co-expression network analysis(WGCNA)and Least absolute shrinkage and selection operator(LASSO)Cox regression.The expression levels of CYB5D2 and TGF-βin HCC cell lines were quantified using Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blotting(WB)assays.Effects of CYB5D2 overexpression on cell proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)marker regulation were assessed in vitro,while in vivo tumorigenicity was evaluated using a xenograft model of HCC in nude mice.Results:In this study,WGCNA identified the turquoise module as significantly associated with HCC,containing 452 DEGs.LASSO Cox regression analysis revealed 9 key prognostic genes,with CYB5D2 being underexpressed in HCC cells and tissues.TGF-βwas negatively correlated with CYB5D2 expression,resulting in poor patient prognosis.Functional assays demonstrated that CYB5D2 overexpression inhibited proliferation,migration,and invasion of HCC cell lines,and altered EMT marker expression.Furthermore,the addition of TGF-βpartially reversed the suppressive effects caused by CYB5D2 overexpression.In vivo,CYB5D2 overexpression significantly reduced tumor growth,indicating its potential as a therapeutic target for HCC.Conclusion:The tumor suppressor function of CYB5D2 in HCC and its interaction with TGF-βoffered fresh information on the molecular pathophysiology of HCC and possible treatment avenues.
基金Supported by National Natural Science Foundation of China,No.82270634.
文摘As one of the most prevalent malignant tumors,hepatocellular carcinoma(HCC)represents a major global public health burden.Traditionally,HCC pathogenesis has been attributed to chronic liver diseases(viral hepatitis,cirrhosis)and aflatoxin exposure.However,with evolving lifestyles and environmental changes,sleep disorders have become increasingly prevalent.Emerging evidence suggest that sleep disorders may contribute to hepatocarcinogenesis through multiple mechanisms,including immunity environment disorder,oxidative stress,metabolic dysregulation,disruption of gut microbiota,and circadian rhythm disruption,thereby influencing disease progression and patient prognosis.This review summarizes epidemiological evidence on the relationship between sleep disorders and HCC incidence,explores the underlying mechanisms through which sleep disorders contribute to HCC,and discusses clinical challenges and potential intervention strategies.Our objective is to provide novel insights into HCC prevention and therapeutic approaches.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide and currently lacks effective treatment options.This is particularly true for advanced HCC,for which conventional therapies often lead to a poor prognosis.AIM To assess the safety and efficacy of transarterial chemoembolization(TACE)with donafenib and immune checkpoint inhibitors(ICIs)for unresectable HCC.METHODS We retrospectively assessed the data of patients with HCC who underwent TACE combined with donafenib and an ICI(tislelizumab or cedilimumab).Patients received oral donafenib daily for 2 weeks before TACE,followed by tislelizumab or cedilimumab 200 mg intravenously on day 1 of a 21-day therapeutic cycle.The primary endpoints were objective response rate,disease control rate,and duration of response according to the modified RECIST criteria.The secondary endpoint was presence of treatment-related adverse events(TRAEs).RESULTS The median follow-up was 7.8 months(95%CI:5.0-11.8 months).The objective response rate was 60.0%(18/30),while the disease control rate was 93.3%.The median duration of response in confirmed responders was 6.6 months(95%CI:1.3-12.9 months).The median progression-free survival was 11.8 months(95%CI:8.3-15.4 months).More than half of the patients survived until the end of the study.Grade>3 TRAEs occurred in 40%of the patients with no grade 5 TRAEs reported.The most common grade 3/4 TRAE was palmar-plantar erythrodysesthesia,a dermatologic condition characterized by painful redness and swelling of the palms and soles,with an incidence of 56.7%.No ICI-related adverse effects were observed.CONCLUSION TACE combined with donafenib and ICI is a promising and safe therapeutic regimen for unresectable HCC.
基金Supported by Shanghai Municipal Hospital Emerging Frontier Technology Joint Project,No.SHDC12019105Shanghai Science and Technology Development Funds,No.24YF2758200National Natural Science Foundation of China,No.82100699.
文摘BACKGROUND The clinical effectiveness of magnetically controlled capsule endoscopy(MCE)is well established.However,problems,such as abdominal distension,insufficient gastric filling,and prolonged gastric retention time,persist with MCE gastric preparations.AIM To compare gastric filling using a carbonated soft drink with that using pure water during MCE.METHODS We performed an open-label randomised controlled trial at the Endoscopy Centre of Changhai Hospital in Shanghai.Patients aged 18-80 years,with or without gastrointestinal symptoms,scheduled for MCE were consecutively recruited.Those who provided informed consent were randomly assigned to the carbonated soft drink group(C group)or water group(W group)in a 1:1 ratio.For patients in the W group,1000 mL of water was ingested to distend the stomach,whereas for patients in the C group,550 mL of carbonated soft drink was provided,and patients were required to drink quickly while minimising burping.The primary endpoint was the number of patients with a gastric filling score of≥4 within 5 minutes after the capsule entered the stomach.RESULTS From December 3,2020 to May 17,2021,252 patients(141 men),aged 18-77 years,were assigned to the C(n=126)and W(n=126)groups.For the primary outcome,123 patients in the C group achieved a gastric filling score of≥4(97.62%vs 80.16%,P<0.0001).More patients in the C group had the highest gastric filling scores within the first 5 min(78.57%vs 29.37%,P<0.0001)and 10 minutes(54.76%vs 13.49%,P<0.0001)after the capsule entered the stomach.More patients in the W group required extra liquid for gastric refilling(1.59%vs 16.67%,P<0.0001).Transpyloric passage of the capsule under magnetic control was successfully performed in 43 patients in the C group(P<0.0001),accompanied by a shorter gastric transit time(53.27±53.83 minutes vs 71.12±52.19 minutes,P=0.001).CONCLUSION Carbonated soft drinks demonstrated superior and more sustained gastric filling compared with those of water alone,with the potential to promote gastric emptying.
基金This study was supported by grants from the National Natural Science Foundation of China(82425049,81972726 and 82273074)Dawn Project Foundation of Shanghai(21SG36)+4 种基金Shanghai Health and Hygiene Discipline Leader Project(2022XD001)Shanghai Out-standing Academic Leader Program(23XD1424900)the Natural Science Foundation of Shanghai(22ZR1477900)Shanghai Science and Technology Committee Rising-Star Program(22QA1411600)the Special Clinical Project of Shanghai Municipal Health Com-mission(20244Y0233)。
文摘Background:Despite advances in surgical treatment,high recurrence after surgery remains a challenge for patients with hepatocellular carcinoma(HCC).This study aimed to investigate the association between compliance to regular follow-up and long-term oncological outcomes among patients undergoing curative resection for HCC.Methods:This multicenter study included patients who underwent curative resection for early-stage HCC between January 2012 and December 2021 at 12 liver surgery centers.Patients were stratified into a regular follow-up group(follow-up every 2–3 months for the first 2 years and every 3–6 months thereafter)and an irregular/no follow-up group.Overall survival(OS),time to recurrence(TTR),and post-recurrence survival(PRS)were compared between the two groups.Results:Among 1544 patients,786(50.9%)underwent regular follow-up during postoperative follow-up.The regular follow-up group had better OS(median:113.4 vs.94.5 months,P=0.010)and PRS(median:37.9 vs.16.3 months,P<0.001)than the irregular/no follow-up group,although TTR was comparable(median:61.4 vs.66.2 months,P=0.161).Furthermore,patients in the regular follow-up group had a lower incidence of tumor beyond the Milan criteria at recurrence(41.6%vs.50.4%,P=0.013)and were more likely to receive curative treatments for recurrence(56.1%vs.49.3%,P=0.061).On multivariate analysis,compliance to regular follow-up was an independent factor associated with better OS[hazard ratio(HR)=0.777,95%confidence interval(CI):0.663–0.910,P=0.002]and PRS(HR=0.523,95%CI:0.428–0.638,P<0.001).Conclusions:Compliance to regular follow-up improved OS and PRS after curative resection for HCC,highlighting the importance of postoperative regular follow-up for early detection of recurrence and timely intervention.
文摘AIM:To investigate the indications for lymph node dissection(LND)in intrahepatic cholangiocarcinoma patients.METHODS:A retrospective analysis was conducted on 124 intrahepatic cholangiocarcinoma(ICC)patients who had undergone surgical resection of ICC from January 2006 to December 2007.Curative resection was attempted for all patients unless there were metastases to lymph nodes(LNs)beyond the hepatoduodenal ligament.Prophylactic LND was performed in patients in whom any enlarged LNs had been suspicious for metastases.The patients were classified according to the LND and LN metastases.Clinicopathologic,operative,and long-term survival data were collected retrospectively.The impact on survival of LND during primary resection was analyzed.RESULTS:Of 53 patients who had undergone hepatic resection with curative intent combined with regional LND,11 had lymph nodes metastases.Whether or not patients without lymph node involvement had undergone LND made no significant difference to their survival(P=0.822).Five patients with multiple tumors and involvement of lymph nodes underwent hepatic resection with LND;their survival curve did not differ significantly from that of the palliative resection group(P=0.744).However,there were significant differences in survival between patients with lymph node involvement and a solitary tumor who underwent hepatic resection with LND and the palliative resection group(median survival time 12 mo vs 6.0 mo,P=0.013).CONCLUSION:ICC patients without lymph node involvement and patients with multiple tumors and lymph node metastases may not benefit from aggressive lymphadenectomy.Routine LND should be considered with discretion.
基金the National Natural Science Foundation of China,No.39770379the National Basic Research Project("973")SUGEN,USA.
文摘AIM To clone and identify the whole cDNA ofMXR7 gene and to find out its expression inhuman HCC,and normal tissues.METHODS The DNA primers were designed andsynthesized according to the whole cDNAsequence of MXR? gene.The cDNA of humanHCC was taken as the template while the cDNA ofMXR7 gene was synthesized by polymerasechain reaction（PCR）.Recombinant DNAconforming to reading frame was constructed byconnecting purified PCR product of the cDNA ofMXR? gene with expression vector pGEX-5X-1 offusion protein.The plasmid MXRT/pGEX-5X-1was identified by sequencing.Using <sup>32</sup>p labeledMXR? cDNA as probe,MXR7 mRNA expressionwas detected by Northern blot analysis in 12different human normal tissues,7 preoperativelyuntreated non-liver tumor tissues,30preoperatively untreated HCC,theparacancerous liver tissues and 12 normal livertissues samples.RESULTS Restriction enzyme and sequenceanalysis confirmed that the insertion sequence invector pGEX-5X-1 was the same as the cDNAsequence of MXR7 gene.Northern blot analysisshowed no expression of MXR? mRNA in 12 kindsof normal human tissues including liver,7 tumortissues in other sites and 12 normal livertissues,the frequencies of MXR7 mRNA expression in HCC and paracancerous livertissues were 76.6% and 13.3%,respectively.The frequency of MXR7 mRNA expression in HCCwithout elevation of serum AFP and in HCC【5cm was 90%（9/10）and 83.3%（5/6）,respectively.CONCLUSION MXR7 mRNA is highly expressedin human HCC,which is specific and occurs at anearly stage of HCC,suggesting MXR7 mRNA canbe a tumor biomarker for HCC.The detection ofMXR7 mRNA expression in the biopsied livertissue is helpful in discovering early subclinicalliver cancer in those with negative serum AFP.
