Traditional Chinese medicine （TCM） is an important part of the treatment of primary liver cancer （PLC） in China; however, the current instructions for the integrative use of traditional Chinese and Western medicin...Traditional Chinese medicine （TCM） is an important part of the treatment of primary liver cancer （PLC） in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical prac-tice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the method- ological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.展开更多
BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclea...BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.展开更多
The liver,the largest solid organ in the body,is susceptible to metabolic diseases and malignant tumors.Studying its physiological and pathological processes helps to optimize the clinical treatment.Organoids are a no...The liver,the largest solid organ in the body,is susceptible to metabolic diseases and malignant tumors.Studying its physiological and pathological processes helps to optimize the clinical treatment.Organoids are a novel tool for studying physical development,disease mechanisms,and high-throughput drug screening due to their similarity in composition,structure,and function to internal organs.Recent studies have shown that stem cells,hepatocytes,or cholangiocytes can form“liver organoids”under the synergistic action of specific extracellular matrix and various signaling molecules.This review outlines techniques for generating liver organoids that maximally recapitulate the liver structure and functions in vitro and thoroughly discusses the customary applications of organoids derived from liver tissue,induced pluripotent stem cells(iPSCs)and liver tumors.In this review,a meticulous analysis is provided of the comparatively advanced culture systems used in the construction of liver cancer-derived organoids.Additionally,we reviewed the progress of liver organoids in disease modeling,drug efficacy,and toxicity evaluation,in hopes of generating innovative ideas for the research and applications of liver organoids.展开更多
AIM: To investigate the long-term results of liver transplantation (LT) for non-acetaminophen fulminant hepatic failure (FHF). METHODS: Over a 20-year period, 29 FHF patients underwent cadaveric whole LT. Most frequen...AIM: To investigate the long-term results of liver transplantation (LT) for non-acetaminophen fulminant hepatic failure (FHF). METHODS: Over a 20-year period, 29 FHF patients underwent cadaveric whole LT. Most frequent causes of FHF were hepatitis B virus and drug-related (not acetaminophen) liver failure. All surviving patients were regularly controlled at the out-patient clinic and none was lost to follow-up. Mean follow-up was 101 mo. RESULTS: One month, one-, five- and ten-year patient survival was 79%, 72%, 68% and 68%, respectively. One month, one-, five- and ten-year graft survival was 69%, 65%, 51% and 38%, respectively. Six patients needed early (< 2 mo) retransplantation, four for primary non-function, one for early acute refractory rejection because of ABO blood group incompatibility, and one for a malignant tumor found in the donor. Two patients with hepatitis B FHF developed cerebral lesions peri-transplantion: One developed irreversible and extensive brain damage leading to death, and one suffered from deep deficits leading to continuous medical care in a specialized institution. CONCLUSION: Long-term outcome of patients transplanted for non-acetaminophen FHF may be excellent. As the quality of life of these patients is also particularly good, LT for FHF is clearly justified, despite lower graft survival compared with LT for other liver diseases.展开更多
Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research h...Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research has uncovered the complex roles of neutrophils as regulators in tumorigenesis,during which neutrophils exhibit a dualistic nature that promotes or inhibits tumor progression.This adaptability is pivotal within the tumor microenvironment(TME).In this review,we provide a comprehensive characterization of neutrophil plasticity and heterogeneity,aiming to illuminate current research findings and discuss potential therapeutic avenues.By delineating the intricate interplay of neutrophils in the TME,this review further underscores the urgent need to understand the dual functions of neutrophils with particular emphasis on the anti-tumor effects to facilitate the development of effective therapeutic strategies against cancer.展开更多
The robotic surgical system has been applied in liver surgery.However,controversies concerns exist regarding a variety of factors including the safety,feasibility,efficacy,and cost-effectiveness of robotic surgery.To ...The robotic surgical system has been applied in liver surgery.However,controversies concerns exist regarding a variety of factors including the safety,feasibility,efficacy,and cost-effectiveness of robotic surgery.To promote the development of robotic hepatectomy,this study aimed to evaluate the current status of robotic hepatectomy and provide sixty experts'consensus and recommendations to promote its development.Based on the World Health Organization Handbook for Guideline Development,a Consensus Steering Group and a Consensus Development Group were established to determine the topics,prepare evidence-based documents,and generate recommendations.The GRADE Grid method and Delphi vote were used to formulate the recommendations.A total of 22 topics were prepared analyzed and widely discussed during the 4 meetings.Based on the published articles and expert panel opinion,7 recommendations were generated by the GRADE method using an evidence-based method,which focused on the safety,feasibility,indication,techniques and cost-effectiveness of hepatectomy.Given that the current evidences were low to very low as evaluated by the GRADE method,further randomized-controlled trials are needed in the future to validate these recommendations.展开更多
AIM:To investigate the efficacy and toxicity of systemic chemotherapy in a retrospective study of patients with hepatocellular carcinoma(HCC)occurring in normal or fibrotic liver without cirrhosis. METHODS:Twenty-four...AIM:To investigate the efficacy and toxicity of systemic chemotherapy in a retrospective study of patients with hepatocellular carcinoma(HCC)occurring in normal or fibrotic liver without cirrhosis. METHODS:Twenty-four patients with metastatic or locally advanced HCC in a normal or a fibrotic liver were given systemic chemotherapy(epirubicin,cis- platin and 5-fluorouracil or epirubicin,cisplatin and capecitabine regimens).Tumor response,time to pro- gression,survival,and toxicity were evaluated. RESULTS:There were 7 women and 17 men,mean age 54±10 years;18 patients had a normal liver and 6 had a fibrotic liver(F1/F2 on biopsy).Mean tumor size was 14 cm,5 patients had portal vein thrombosis and 7 had metastasis.Patients received a median of 4 chemotherapy sessions.Overall tolerance was good. There were 5 partial responses(objective response rate =22%),and tumor control rate was 52%.Second line surgical resection was possible in two patients.Median survival was 11 mo,and 1-and 2-year overall survival rates were 50%±10%and 32%±11%,respectively. CONCLUSION:In patients with HCC in a non-cirrhotic liver,chemotherapy was well tolerated and associated with an objective response rate of 22%,including two patients who underwent secondary surgical resection.展开更多
The robotic liver resection(RLR)has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system,however,controversies still exist.Base...The robotic liver resection(RLR)has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system,however,controversies still exist.Based on the foundation of the previous consensus statement,this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice.The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine(EBM).Relevant literature was reviewed and analyzed by the evidence evaluation group.According to the WHO Handbook for Guideline Development,the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022,a total of 14 recommendations were generated.Among them were 8 recommendations formulated by the GRADE method,and the remaining 6 recommendations were formulated based on literature review and experts’opinion due to insufficient EBM results.This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.展开更多
Cancer metastasis remains one of the most confounding questions in oncology1,2.Although current cutting-edge techniques enable very early detection of tumors,profiling whether a tumor has already begun to spread and w...Cancer metastasis remains one of the most confounding questions in oncology1,2.Although current cutting-edge techniques enable very early detection of tumors,profiling whether a tumor has already begun to spread and where it has attempted to colonize remains a major hurdle.Indeed,metastatic seeding events exhibit remarkable temporal and spatial heterogeneity,wherein the origin(primary site)and destination(metastatic site)are highly dynamic.For example,liver metastasis is particularly common and remains a leading cause of mortality3.展开更多
The covalently closed circular DNA(cccDNA)of HBV plays a crucial role in viral persistence and is also a risk factor for developing HBV-induced diseases,including liver fibrosis.Stimulator of interferon genes(STING),a...The covalently closed circular DNA(cccDNA)of HBV plays a crucial role in viral persistence and is also a risk factor for developing HBV-induced diseases,including liver fibrosis.Stimulator of interferon genes(STING),a master regulator of DNA-mediated innate immune activation,is a potential therapeutic target for viral infection and virus-related diseases.In this study,agonist-induced STING signaling activation in macrophages was revealed to inhibit cccDNA-mediated transcription and HBV replication via epigenetic modification in hepatocytes.Notably,STING activation could efficiently attenuate the severity of liver injury and fibrosis in a chronic recombinant cccDNA(rcccDNA)mouse model,which is a proven suitable research platform for HBV-induced fibrosis.Mechanistically,STING-activated autophagic flux could suppress macrophage inflammasome activation,leading to the amelioration of liver injury and HBV-induced fibrosis.Overall,the activation of STING signaling could inhibit HBV replication through epigenetic suppression of cccDNA and alleviate HBV-induced liver fibrosis through the suppression of macrophage inflammasome activation by activating autophagic flux in a chronic HBV mouse model.This study suggests that targeting the STING signaling pathway may be an important therapeutic strategy to protect against persistent HBV replication and HBV-induced fibrosis.展开更多
(PHLF)is a severe complication and main cause of death in patients undergoing hepatectomy.The aim of this study was to build a predictive model of PHLF in patients undergoing hepatectomy.Methods:We retrospectively ana...(PHLF)is a severe complication and main cause of death in patients undergoing hepatectomy.The aim of this study was to build a predictive model of PHLF in patients undergoing hepatectomy.Methods:We retrospectively analyzed patients undergoing hepatectomy at Zhongshan Hospital,Fudan University from July 2015 to June 2018,and randomly divided them into development and internal validation cohorts.External validation was performed in an independent cohort.Least absolute shrinkage and selection operator(commonly referred to as LASSO)logistic regression was applied to identify predictors of PHLF,and multivariate binary logistic regression analysis was performed to establish the predictive model,which was visualized with a nomogram.Results:A total of 492 eligible patients were analyzed.LASSO and multivariate analysis identified three preoperative variables,total bilirubin(p=0.001),international normalized ratio(p<0.001)and platelet count(p=0.004),and two intraoperative variables,extent of resection(p=0.002)and blood loss(p=0.004),as independent predictors of PHLF.The area under receiver operating characteristic curve(referred to as AUROC)of the predictive model was 0.838 and outperformed the model for end-stage liver disease score,albumin-bilirubin score and platelet-albumin-bilirubin score(AUROCs:0.723,0.695 and 0.663,respectively;p<0.001 for all).The optimal cut-off value of the predictive model was 14.7.External validation showed the model could predict PHLF accurately and distinguish high-risk patients.Conclusions:PHLF can be accurately predicted by this model in patients undergoing hepatectomy,which may significantly contribute to the postoperative care of these patients.展开更多
References Show full outline Cited by(1)Figures(3)Unlabelled figure Fig.1.Population diversity of DNA methylation Fig.2.Genetic contribution to the population differentiation in DNA methylation…Extras(1)Supplementary...References Show full outline Cited by(1)Figures(3)Unlabelled figure Fig.1.Population diversity of DNA methylation Fig.2.Genetic contribution to the population differentiation in DNA methylation…Extras(1)Supplementary Data 1 Elsevier Science Bulletin Volume 70,Issue 5,15 March 2025,Pages 638-642 Science Bulletin Short Communication DNA methylation and genetic regulation in natural populations of East Asian and mixed Eurasian ancestry Author links open overlay panel Shuangshuang Cheng a,Zhilin Ning b,Yan Lu a e,Yuhan Du a,Xiaonan Yang c,Minghui Li c,Dilinuer Maimaitiyiming d,Shuhua Xu a f a State Key Laboratory of Genetic Engineering,Human Phenome Institute,Zhangjiang Fudan International Innovation Center,Center for Evolutionary Biology,School of Life Sciences,Department of Liver Surgery and Transplantation Liver Cancer Institute,Zhongshan Hospital,Fudan University,Shanghai 200032,China b Key Laboratory of Computational Biology,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China c Sinotech Genomics Co.,Ltd.,Shanghai 200120,China d The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China e Ministry of Education Key Laboratory of Contemporary Anthropology,Fudan University,Shanghai 200438,China f School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China Received 27 March 2024,Revised 16 July 2024,Accepted 30 September 2024,Available online 15 October 2024,Version of Record 10 March 2025.What do these dates mean?Show less Add to Mendeley Share Cite https://doi.org/10.1016/j.scib.2024.10.006 Get rights and content Under a Creative Commons license Open access Graphical abstract Download:Download high-res image(109KB)Download:Download full-size image Previous article Next article As an important epigenetic marker,DNA methylation(DNAm)is a stably inherited epigenetic modification that plays an important role in mammalian epigenetics.DNAm is influenced by genetic and environmental factors[1],and has different functions in different genomic contexts.It has been suggested that a large proportion of DNAm differences are associated with allele frequency divergence[2].In addition,significant differences in cis-DNA methylation quantitative trait loci were found in three Southeast Asian populations[3].The epigenetic structure of DNAm in several populations in China has also been reported recently[4].Some genome-wide studies have identified ancestral origins and population relationships;for example,the Uyghurs have approximately a half-Eastern and half-Western genetic composition[5],[6].Notably,a recent study explored the genetic basis of highly differentiated gene expression with east–west origins in Uyghurs[7].However,our understanding of DNAm profiles and their genetic basis remains limited,particularly in 1:1 mixed-descent populations.In this study,we constructed a DNAm map with data from 92 Uyghurs(XJU)and 33 Han Chinese(HAN)individuals.The procedures followed the ethical standards of the Responsible Committee on Human Experimentation and were approved by the Biomedical Research Ethics Committee of Shanghai Institutes for Biological Sciences(ER-SIBS-261408)and the Helsinki Declaration of 1975(revised in 2000).Each individual was the offspring of a nonconsanguineous marriage of members of the same nationality within three generations.We identified the highly differentiated DNAm positions and regions between HAN and XJU.We then examined the correlation between the level of genetic differences and the level of DNAm differences.Finally,we studied the relationship between the genomic and epigenetic data at the global and local levels.展开更多
Introduction Liver transplantation(LT)benefits patients with decompensated liver cirrhosis,acute liver failure,or hepatocellular carcinoma.The greatest challenge in LT is the insufficient number of donors for the grow...Introduction Liver transplantation(LT)benefits patients with decompensated liver cirrhosis,acute liver failure,or hepatocellular carcinoma.The greatest challenge in LT is the insufficient number of donors for the growing number of transplantation candidates.Various surgical strategies have been adopted to overcome the increasing donor-recipient disparity,including sequential/“domino”transplantation,split LT,use of marginal livers,and living donor LT(LDLT).To ensure the safety of donors and recipients,dual-graft LT may be considered(1).Herein,we describe the first successful hybrid-dual-graft LT in an obese patient requiring urgent LT,which involved transplantation of an otherwise-wasted resected liver lobe from a patient with a benign hepatic tumor and an inadequate-size living donor graft from the recipient’s father.展开更多
Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85%of all cancer cases in the country.Several g...Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85%of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.展开更多
In recent years,significant advances have been achieved in liver cancer management with the development of artificial intelligence(AI).AI-based pathological analysis can extract crucial information from whole slide im...In recent years,significant advances have been achieved in liver cancer management with the development of artificial intelligence(AI).AI-based pathological analysis can extract crucial information from whole slide images to assist clinicians in all aspects from diagnosis to prognosis and molecular profiling.However,AI techniques have a“black box”nature,which means that interpretability is of utmost importance because it is key to ensuring the reliability of the methods and building trust among clinicians for actual clinical implementation.In this paper,we provide an overview of current technical advancements in the AI-based pathological analysis of liver cancer,and delve into the strategies used in recent studies to unravel the“black box”of AI's decision-making process.展开更多
BACKGROUND Improving the intraoperative and postoperative performance of laparoscopic hepatectomy was quite a challenge for liver surgeons.AIM To determine the benefits of indocyanine green(ICG)fluorescence imaging in...BACKGROUND Improving the intraoperative and postoperative performance of laparoscopic hepatectomy was quite a challenge for liver surgeons.AIM To determine the benefits of indocyanine green(ICG)fluorescence imaging in patients with hepatocellular carcinoma(HCC)who underwent laparoscopic hepatectomy during and after surgery.METHODS We retrospectively collected the clinicopathological data of 107 patients who successfully underwent laparoscopic hepatectomy at Zhongshan Hospital(Xiamen),Fudan University from June 2022 to June 2023.Whether using the ICG fluorescence imaging technique,we divided them into the ICG and non-ICG groups.To eliminate statistical bias,a 1:1 propensity score matching analysis was conducted.The comparison of perioperative outcomes,including inflammationrelated markers and progression-free survival,was analyzed statistically.RESULTS Intraoperatively,the ICG group exhibited lower blood loss,a shorter surgical time,lower hepatic inflow occlusion(HIO)frequency,and a shorter total HIO time.Postoperatively,the participation of ICG resulted in a shorter duration of hospitalization(6.5 vs 7.6 days,P=0.03)and postoperative inflammatory response attenuation(lower neutrophil-lymphocyte ratio on the first day after surgery and platelet-lymphocyte ratio on the third day,P<0.05).Although the differences were not significant,the levels of all inflammation-related markers were lower in the ICG group.The rates of postoperative complications and the survival analyses,including progression-free and overall survivals showed no significant difference between the groups.CONCLUSION The involvement of ICG fluorescence imaging may lead to improved perioperative outcomes,especially postoperative inflammatory response attenuation,and ultimately improve HCC patients’recovery after surgery.展开更多
Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Ge...Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Genetic variants that regulate gene expression,known as expression quantitative trait loci(eQTL),are primarily shaped by human migration history and evolutionary forces,likewise,regulation of gene expression in principle could have been influenced by these events.Therefore,a comprehensive understanding of how human evolution impacts eQTL offers important insights into how phenotypic diversity is shaped.Recent studies,however,suggest that eQTL is enriched in genes that are selectively constrained.Whether eQTL is minimally affected by selective pressures remains an open question and requires comprehensive investigations.In addition,such studies are primarily dominated by the major populations of European ancestry,leaving many marginalized populations underrepresented.These observations indicate there exists a fundamental knowledge gap in the role of genomics variation on phenotypic diversity,which potentially hinders precision medicine.This article aims to revisit the abundance of eQTL across diverse populations and provide an overview of their impact from the population and evolutionary genetics perspective,subsequently discuss their influence on phenomics,as well as challenges and opportunities in the applications to precision medicine.展开更多
Liver cancer,mostly hepatocellular carcinoma(HCC),is the second leading cause of cancer mortality globally.Most patients were diagnosed at an advanced stage,and systemic therapy is the standard of care.All the approve...Liver cancer,mostly hepatocellular carcinoma(HCC),is the second leading cause of cancer mortality globally.Most patients were diagnosed at an advanced stage,and systemic therapy is the standard of care.All the approved systemic therapies for HCC are molecular targeted therapies with anti-angiogenic effects targeting the vascular endothelial growth factor signaling pathway.Sorafenib and lenvatinib are the first-line treatment,and regorafenib,ramucirumab,and cabozantinib are second-line treatment options.Although anti-PD-1 antibodies,including nivolumab and pembrolizumab,demonstrated promising anti-tumor effects as monotherapy for advanced HCC in phase II clinical trials,both failed in phase III studies.Anti-angiogenic treatment remains the backbone of systemic therapy for HCC.In this review,we summarized the approved anti-angiogenic medicines and discussed the potential strategies to improve the efficacy of anti-angiogenic therapy,including combination therapy with other treatments,and discussed the approaches to overcome the drawbacks of anti-angiogenic therapies.展开更多
Advances in antibody engineering have led to the generation of more innovative antibody drugs,such as bispecific antibodies(bs Abs).Following the success associated with blinatumomab,bs Abs have attracted enormous int...Advances in antibody engineering have led to the generation of more innovative antibody drugs,such as bispecific antibodies(bs Abs).Following the success associated with blinatumomab,bs Abs have attracted enormous interest in the field of cancer immunotherapy.By specifically targeting two different antigens,bs Abs reduce the distance between tumor and immune cells,thereby enhancing tumor killing directly.There are several mechanisms of action upon which bs Abs have been exploited.Accumulating experience on checkpoint-based therapy has promoted the clinical transformation of bs Abs targeting immunomodulatory checkpoints.Cadonilimab(PD-1×CTLA-4)is the first approved bs Ab targeting dual inhibitory checkpoints,which confirms the feasibility of bs Abs in immunotherapy.In this review we analyzed the mechanisms by which bs Abs targeting immunomodulatory checkpoints and their emerging applications in cancer immunotherapy.展开更多
Background:Intrahepatic cholangiocarcinoma(ICC)is a highly metastatic cancer.^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)enables sensitive tumor and metastasis detectio...Background:Intrahepatic cholangiocarcinoma(ICC)is a highly metastatic cancer.^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)enables sensitive tumor and metastasis detection.Our aim is to evaluate the influence of pre-treatment PET/CT on the N-and M-staging and subsequent clinical management in ICC patients.Methods:Between August 2010 and August 2018,660 consecutive ICC patients,without prior anti-tumor treatments nor other malignancies,were enrolled.The diagnostic performance of PET/CT on the N-and M-staging was compared with conventional imaging,and the preoperative staging accuracy and treatment re-allocation by PET/CT were retrospectively calculated.Survival difference was compared between patients receiving PET/CT or not after propensity score matching.Results:Patients were divided into group A(n=291)and group B(n=369)according to whether PET/CT was performed.Among 291 patients with both PET/CT and conventional imaging for staging in group A,PET/CT showed significantly higher sensitivity(83.0%vs.70.5%,P=0.001),specificity(88.3%vs.74.9%,P<0.001)and accuracy(86.3%vs.73.2%,P<0.001)than conventional imaging in diagnosing regional lymph node metastasis,as well as higher sensitivity(87.8%vs.67.6%,P<0.001)and accuracy(93.5%vs.89.3%,P=0.023)in diagnosing distant metastasis.Overall,PET/CT improved the accuracy of preoperative staging from 60.1%to 71.8%(P<0.001),and modified clinical treatment strategy in 5.8%(17/291)of ICC patients,with unique roles in different tumor-node-metastasis(TNM)stages.High tumor-to-non-tumor ratio(TNR)predicted poor overall survival[hazard ratio(HR)=2.17;95%confidence interval(CI):1.49-3.15;P<0.001].Furthermore,patients performing PET/CT had longer overall survival compared with those without PET/CT(HR=0.74;95%CI:0.58-0.93;P=0.011)after propensity score matching.Conclusions:PET/CT was valuable for diagnosing regional lymph node metastasis and distant metastasis in ICC patients,and facilitated accurate tumor staging and optimal treatment allocation.展开更多
基金funded by the Shanghai Municipal Commission of Health and Family Planning(Grant Number ZY3-LCPT-2-1004)National Natural Science Foundation of China(Grant Number81503459)E-Institutes of Shanghai Municipal Education Commission(Grant Number E03008)
文摘Traditional Chinese medicine （TCM） is an important part of the treatment of primary liver cancer （PLC） in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical prac-tice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the method- ological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.
基金Supported by National Natural Science Foundation of China,No.81670514 and No.81702337Scientific Research Project of Shanghai Municipal Health Commission,No.202040065Natural Science Foundation of Shanghai Scientific and Technological Project of Innovative Action,No.20ZR1411900.
文摘BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.
基金supported by Research Projects from the Science and Technology Commission of Shanghai Municipality(No.21JC1401200).
文摘The liver,the largest solid organ in the body,is susceptible to metabolic diseases and malignant tumors.Studying its physiological and pathological processes helps to optimize the clinical treatment.Organoids are a novel tool for studying physical development,disease mechanisms,and high-throughput drug screening due to their similarity in composition,structure,and function to internal organs.Recent studies have shown that stem cells,hepatocytes,or cholangiocytes can form“liver organoids”under the synergistic action of specific extracellular matrix and various signaling molecules.This review outlines techniques for generating liver organoids that maximally recapitulate the liver structure and functions in vitro and thoroughly discusses the customary applications of organoids derived from liver tissue,induced pluripotent stem cells(iPSCs)and liver tumors.In this review,a meticulous analysis is provided of the comparatively advanced culture systems used in the construction of liver cancer-derived organoids.Additionally,we reviewed the progress of liver organoids in disease modeling,drug efficacy,and toxicity evaluation,in hopes of generating innovative ideas for the research and applications of liver organoids.
文摘AIM: To investigate the long-term results of liver transplantation (LT) for non-acetaminophen fulminant hepatic failure (FHF). METHODS: Over a 20-year period, 29 FHF patients underwent cadaveric whole LT. Most frequent causes of FHF were hepatitis B virus and drug-related (not acetaminophen) liver failure. All surviving patients were regularly controlled at the out-patient clinic and none was lost to follow-up. Mean follow-up was 101 mo. RESULTS: One month, one-, five- and ten-year patient survival was 79%, 72%, 68% and 68%, respectively. One month, one-, five- and ten-year graft survival was 69%, 65%, 51% and 38%, respectively. Six patients needed early (< 2 mo) retransplantation, four for primary non-function, one for early acute refractory rejection because of ABO blood group incompatibility, and one for a malignant tumor found in the donor. Two patients with hepatitis B FHF developed cerebral lesions peri-transplantion: One developed irreversible and extensive brain damage leading to death, and one suffered from deep deficits leading to continuous medical care in a specialized institution. CONCLUSION: Long-term outcome of patients transplanted for non-acetaminophen FHF may be excellent. As the quality of life of these patients is also particularly good, LT for FHF is clearly justified, despite lower graft survival compared with LT for other liver diseases.
基金supported by the National Natural Science Foundation of China(Grant Nos.82130077,81961128025,and 82121002)the Research Projects from the Science and Technology Commission of Shanghai Municipality(Grant Nos.21JC1401200,20JC1418900,and 21JC1410100)to QG,the China National Postdoctoral Program for Innovative Talents(Grant No.BX20240090)the China Postdoctoral Science Foundation(Grant No.2024M750551)to MZ.
文摘Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research has uncovered the complex roles of neutrophils as regulators in tumorigenesis,during which neutrophils exhibit a dualistic nature that promotes or inhibits tumor progression.This adaptability is pivotal within the tumor microenvironment(TME).In this review,we provide a comprehensive characterization of neutrophil plasticity and heterogeneity,aiming to illuminate current research findings and discuss potential therapeutic avenues.By delineating the intricate interplay of neutrophils in the TME,this review further underscores the urgent need to understand the dual functions of neutrophils with particular emphasis on the anti-tumor effects to facilitate the development of effective therapeutic strategies against cancer.
基金Supported by National Key Research and Development Program of China,No.2017YFC0110405National Natural Science Foundation of China,No.81500499
文摘The robotic surgical system has been applied in liver surgery.However,controversies concerns exist regarding a variety of factors including the safety,feasibility,efficacy,and cost-effectiveness of robotic surgery.To promote the development of robotic hepatectomy,this study aimed to evaluate the current status of robotic hepatectomy and provide sixty experts'consensus and recommendations to promote its development.Based on the World Health Organization Handbook for Guideline Development,a Consensus Steering Group and a Consensus Development Group were established to determine the topics,prepare evidence-based documents,and generate recommendations.The GRADE Grid method and Delphi vote were used to formulate the recommendations.A total of 22 topics were prepared analyzed and widely discussed during the 4 meetings.Based on the published articles and expert panel opinion,7 recommendations were generated by the GRADE method using an evidence-based method,which focused on the safety,feasibility,indication,techniques and cost-effectiveness of hepatectomy.Given that the current evidences were low to very low as evaluated by the GRADE method,further randomized-controlled trials are needed in the future to validate these recommendations.
文摘AIM:To investigate the efficacy and toxicity of systemic chemotherapy in a retrospective study of patients with hepatocellular carcinoma(HCC)occurring in normal or fibrotic liver without cirrhosis. METHODS:Twenty-four patients with metastatic or locally advanced HCC in a normal or a fibrotic liver were given systemic chemotherapy(epirubicin,cis- platin and 5-fluorouracil or epirubicin,cisplatin and capecitabine regimens).Tumor response,time to pro- gression,survival,and toxicity were evaluated. RESULTS:There were 7 women and 17 men,mean age 54±10 years;18 patients had a normal liver and 6 had a fibrotic liver(F1/F2 on biopsy).Mean tumor size was 14 cm,5 patients had portal vein thrombosis and 7 had metastasis.Patients received a median of 4 chemotherapy sessions.Overall tolerance was good. There were 5 partial responses(objective response rate =22%),and tumor control rate was 52%.Second line surgical resection was possible in two patients.Median survival was 11 mo,and 1-and 2-year overall survival rates were 50%±10%and 32%±11%,respectively. CONCLUSION:In patients with HCC in a non-cirrhotic liver,chemotherapy was well tolerated and associated with an objective response rate of 22%,including two patients who underwent secondary surgical resection.
文摘The robotic liver resection(RLR)has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system,however,controversies still exist.Based on the foundation of the previous consensus statement,this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice.The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine(EBM).Relevant literature was reviewed and analyzed by the evidence evaluation group.According to the WHO Handbook for Guideline Development,the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022,a total of 14 recommendations were generated.Among them were 8 recommendations formulated by the GRADE method,and the remaining 6 recommendations were formulated based on literature review and experts’opinion due to insufficient EBM results.This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.
基金supported by the National Natural Science Foundation of China(Grant Nos.81961128025 and 91942313)Program of Shanghai Academic Research Leader(Grant No.19XD1420700)+1 种基金Shanghai Municipal Key Clinical Specialtyand Sanming Project of Medicine in Shenzhen(Grant No.SZSM202003009).
文摘Cancer metastasis remains one of the most confounding questions in oncology1,2.Although current cutting-edge techniques enable very early detection of tumors,profiling whether a tumor has already begun to spread and where it has attempted to colonize remains a major hurdle.Indeed,metastatic seeding events exhibit remarkable temporal and spatial heterogeneity,wherein the origin(primary site)and destination(metastatic site)are highly dynamic.For example,liver metastasis is particularly common and remains a leading cause of mortality3.
基金This work was supported by grants from the National Natural Science Foundation of China(C31872731,C32070910,C31470839)Zhengyi Scholar Foundation of School of Basic Medical Sciences,Fudan University(S25-01).
文摘The covalently closed circular DNA(cccDNA)of HBV plays a crucial role in viral persistence and is also a risk factor for developing HBV-induced diseases,including liver fibrosis.Stimulator of interferon genes(STING),a master regulator of DNA-mediated innate immune activation,is a potential therapeutic target for viral infection and virus-related diseases.In this study,agonist-induced STING signaling activation in macrophages was revealed to inhibit cccDNA-mediated transcription and HBV replication via epigenetic modification in hepatocytes.Notably,STING activation could efficiently attenuate the severity of liver injury and fibrosis in a chronic recombinant cccDNA(rcccDNA)mouse model,which is a proven suitable research platform for HBV-induced fibrosis.Mechanistically,STING-activated autophagic flux could suppress macrophage inflammasome activation,leading to the amelioration of liver injury and HBV-induced fibrosis.Overall,the activation of STING signaling could inhibit HBV replication through epigenetic suppression of cccDNA and alleviate HBV-induced liver fibrosis through the suppression of macrophage inflammasome activation by activating autophagic flux in a chronic HBV mouse model.This study suggests that targeting the STING signaling pathway may be an important therapeutic strategy to protect against persistent HBV replication and HBV-induced fibrosis.
基金This work was supported by the Leading Investigator Program of the Shanghai municipal government(17XD1401100)the National Key Basic Research Program(973 Program+1 种基金2015CB554005)from the Ministry of Science and Technology of Chinathe National Natural Science Foundation of China(81672326 and 81871928,and 81871929).
文摘(PHLF)is a severe complication and main cause of death in patients undergoing hepatectomy.The aim of this study was to build a predictive model of PHLF in patients undergoing hepatectomy.Methods:We retrospectively analyzed patients undergoing hepatectomy at Zhongshan Hospital,Fudan University from July 2015 to June 2018,and randomly divided them into development and internal validation cohorts.External validation was performed in an independent cohort.Least absolute shrinkage and selection operator(commonly referred to as LASSO)logistic regression was applied to identify predictors of PHLF,and multivariate binary logistic regression analysis was performed to establish the predictive model,which was visualized with a nomogram.Results:A total of 492 eligible patients were analyzed.LASSO and multivariate analysis identified three preoperative variables,total bilirubin(p=0.001),international normalized ratio(p<0.001)and platelet count(p=0.004),and two intraoperative variables,extent of resection(p=0.002)and blood loss(p=0.004),as independent predictors of PHLF.The area under receiver operating characteristic curve(referred to as AUROC)of the predictive model was 0.838 and outperformed the model for end-stage liver disease score,albumin-bilirubin score and platelet-albumin-bilirubin score(AUROCs:0.723,0.695 and 0.663,respectively;p<0.001 for all).The optimal cut-off value of the predictive model was 14.7.External validation showed the model could predict PHLF accurately and distinguish high-risk patients.Conclusions:PHLF can be accurately predicted by this model in patients undergoing hepatectomy,which may significantly contribute to the postoperative care of these patients.
基金National Key Research and Development Program of China(2023YFC2605400)National Natural Science Foundation of China(32030020,32288101,and 32470649)+2 种基金Shanghai Science and Technology Commission Program(23JS1410100)Office of Global Partnerships(Key Projects Development Fund)The computational work in this study was supported by the CFFF Computing Platform of Fudan University.The funders had no role in the study design,data collection,analysis,decision to publish,or preparation of the manuscript.
文摘References Show full outline Cited by(1)Figures(3)Unlabelled figure Fig.1.Population diversity of DNA methylation Fig.2.Genetic contribution to the population differentiation in DNA methylation…Extras(1)Supplementary Data 1 Elsevier Science Bulletin Volume 70,Issue 5,15 March 2025,Pages 638-642 Science Bulletin Short Communication DNA methylation and genetic regulation in natural populations of East Asian and mixed Eurasian ancestry Author links open overlay panel Shuangshuang Cheng a,Zhilin Ning b,Yan Lu a e,Yuhan Du a,Xiaonan Yang c,Minghui Li c,Dilinuer Maimaitiyiming d,Shuhua Xu a f a State Key Laboratory of Genetic Engineering,Human Phenome Institute,Zhangjiang Fudan International Innovation Center,Center for Evolutionary Biology,School of Life Sciences,Department of Liver Surgery and Transplantation Liver Cancer Institute,Zhongshan Hospital,Fudan University,Shanghai 200032,China b Key Laboratory of Computational Biology,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China c Sinotech Genomics Co.,Ltd.,Shanghai 200120,China d The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China e Ministry of Education Key Laboratory of Contemporary Anthropology,Fudan University,Shanghai 200438,China f School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China Received 27 March 2024,Revised 16 July 2024,Accepted 30 September 2024,Available online 15 October 2024,Version of Record 10 March 2025.What do these dates mean?Show less Add to Mendeley Share Cite https://doi.org/10.1016/j.scib.2024.10.006 Get rights and content Under a Creative Commons license Open access Graphical abstract Download:Download high-res image(109KB)Download:Download full-size image Previous article Next article As an important epigenetic marker,DNA methylation(DNAm)is a stably inherited epigenetic modification that plays an important role in mammalian epigenetics.DNAm is influenced by genetic and environmental factors[1],and has different functions in different genomic contexts.It has been suggested that a large proportion of DNAm differences are associated with allele frequency divergence[2].In addition,significant differences in cis-DNA methylation quantitative trait loci were found in three Southeast Asian populations[3].The epigenetic structure of DNAm in several populations in China has also been reported recently[4].Some genome-wide studies have identified ancestral origins and population relationships;for example,the Uyghurs have approximately a half-Eastern and half-Western genetic composition[5],[6].Notably,a recent study explored the genetic basis of highly differentiated gene expression with east–west origins in Uyghurs[7].However,our understanding of DNAm profiles and their genetic basis remains limited,particularly in 1:1 mixed-descent populations.In this study,we constructed a DNAm map with data from 92 Uyghurs(XJU)and 33 Han Chinese(HAN)individuals.The procedures followed the ethical standards of the Responsible Committee on Human Experimentation and were approved by the Biomedical Research Ethics Committee of Shanghai Institutes for Biological Sciences(ER-SIBS-261408)and the Helsinki Declaration of 1975(revised in 2000).Each individual was the offspring of a nonconsanguineous marriage of members of the same nationality within three generations.We identified the highly differentiated DNAm positions and regions between HAN and XJU.We then examined the correlation between the level of genetic differences and the level of DNAm differences.Finally,we studied the relationship between the genomic and epigenetic data at the global and local levels.
基金supported by the National Natural Science Foundation of China(Nos.82150004,81830102),and Shanghai Municipal Key Clinical Specialty.
文摘Introduction Liver transplantation(LT)benefits patients with decompensated liver cirrhosis,acute liver failure,or hepatocellular carcinoma.The greatest challenge in LT is the insufficient number of donors for the growing number of transplantation candidates.Various surgical strategies have been adopted to overcome the increasing donor-recipient disparity,including sequential/“domino”transplantation,split LT,use of marginal livers,and living donor LT(LDLT).To ensure the safety of donors and recipients,dual-graft LT may be considered(1).Herein,we describe the first successful hybrid-dual-graft LT in an obese patient requiring urgent LT,which involved transplantation of an otherwise-wasted resected liver lobe from a patient with a benign hepatic tumor and an inadequate-size living donor graft from the recipient’s father.
基金funded by the National Natural Science Foundation of China(No.82272956).
文摘Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85%of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.
基金supported by the National Natural Science Foundation of China(Nos 81961128025 and 82273187)the Research Projects from the Science and Technology Commission of Shanghai Municipality(Nos 21JC1401200 and 20JC1418900)the Natural Science Foundation of Fujian Province(No.2023J05292).
文摘In recent years,significant advances have been achieved in liver cancer management with the development of artificial intelligence(AI).AI-based pathological analysis can extract crucial information from whole slide images to assist clinicians in all aspects from diagnosis to prognosis and molecular profiling.However,AI techniques have a“black box”nature,which means that interpretability is of utmost importance because it is key to ensuring the reliability of the methods and building trust among clinicians for actual clinical implementation.In this paper,we provide an overview of current technical advancements in the AI-based pathological analysis of liver cancer,and delve into the strategies used in recent studies to unravel the“black box”of AI's decision-making process.
基金Supported by the Incubation Project of Zhongshan Hospital(Xiamen),Fudan University,No.2019ZSXMYS15the Clinical Research Center for Precision Medicine of Abdominal Tumor of Fujian Province+1 种基金the Key Clinical Specialty Discipline Construction Program of Fujian ProvinceXiamen Medical and Health Guidance Project,No.3502Z20244ZD1103.
文摘BACKGROUND Improving the intraoperative and postoperative performance of laparoscopic hepatectomy was quite a challenge for liver surgeons.AIM To determine the benefits of indocyanine green(ICG)fluorescence imaging in patients with hepatocellular carcinoma(HCC)who underwent laparoscopic hepatectomy during and after surgery.METHODS We retrospectively collected the clinicopathological data of 107 patients who successfully underwent laparoscopic hepatectomy at Zhongshan Hospital(Xiamen),Fudan University from June 2022 to June 2023.Whether using the ICG fluorescence imaging technique,we divided them into the ICG and non-ICG groups.To eliminate statistical bias,a 1:1 propensity score matching analysis was conducted.The comparison of perioperative outcomes,including inflammationrelated markers and progression-free survival,was analyzed statistically.RESULTS Intraoperatively,the ICG group exhibited lower blood loss,a shorter surgical time,lower hepatic inflow occlusion(HIO)frequency,and a shorter total HIO time.Postoperatively,the participation of ICG resulted in a shorter duration of hospitalization(6.5 vs 7.6 days,P=0.03)and postoperative inflammatory response attenuation(lower neutrophil-lymphocyte ratio on the first day after surgery and platelet-lymphocyte ratio on the third day,P<0.05).Although the differences were not significant,the levels of all inflammation-related markers were lower in the ICG group.The rates of postoperative complications and the survival analyses,including progression-free and overall survivals showed no significant difference between the groups.CONCLUSION The involvement of ICG fluorescence imaging may lead to improved perioperative outcomes,especially postoperative inflammatory response attenuation,and ultimately improve HCC patients’recovery after surgery.
基金supported by the Ministry of Higher Education(MOHE)Malaysia through Fundamental Research Grant Scheme(FRGS)with project code:FRGS/1/2021/STG01/UCSI/01/.SX was funded by the National Natural Science Foundation of China(NSFC)grants 32030020 and 32288101funded by the NSFC grant 32270665.
文摘Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Genetic variants that regulate gene expression,known as expression quantitative trait loci(eQTL),are primarily shaped by human migration history and evolutionary forces,likewise,regulation of gene expression in principle could have been influenced by these events.Therefore,a comprehensive understanding of how human evolution impacts eQTL offers important insights into how phenotypic diversity is shaped.Recent studies,however,suggest that eQTL is enriched in genes that are selectively constrained.Whether eQTL is minimally affected by selective pressures remains an open question and requires comprehensive investigations.In addition,such studies are primarily dominated by the major populations of European ancestry,leaving many marginalized populations underrepresented.These observations indicate there exists a fundamental knowledge gap in the role of genomics variation on phenotypic diversity,which potentially hinders precision medicine.This article aims to revisit the abundance of eQTL across diverse populations and provide an overview of their impact from the population and evolutionary genetics perspective,subsequently discuss their influence on phenomics,as well as challenges and opportunities in the applications to precision medicine.
基金This work was supported by the Leading Investigator Program of Shanghai municipal government(17XD1401100)the National Key Basic Research Program(973 Program,2015CB554005)the National Natural Science Foundation of China(81372655,81472224 and 81672326)to HCS.
文摘Liver cancer,mostly hepatocellular carcinoma(HCC),is the second leading cause of cancer mortality globally.Most patients were diagnosed at an advanced stage,and systemic therapy is the standard of care.All the approved systemic therapies for HCC are molecular targeted therapies with anti-angiogenic effects targeting the vascular endothelial growth factor signaling pathway.Sorafenib and lenvatinib are the first-line treatment,and regorafenib,ramucirumab,and cabozantinib are second-line treatment options.Although anti-PD-1 antibodies,including nivolumab and pembrolizumab,demonstrated promising anti-tumor effects as monotherapy for advanced HCC in phase II clinical trials,both failed in phase III studies.Anti-angiogenic treatment remains the backbone of systemic therapy for HCC.In this review,we summarized the approved anti-angiogenic medicines and discussed the potential strategies to improve the efficacy of anti-angiogenic therapy,including combination therapy with other treatments,and discussed the approaches to overcome the drawbacks of anti-angiogenic therapies.
基金supported by the National Natural Science Foundation of China(Grant Nos.82130077 and 81961128025)。
文摘Advances in antibody engineering have led to the generation of more innovative antibody drugs,such as bispecific antibodies(bs Abs).Following the success associated with blinatumomab,bs Abs have attracted enormous interest in the field of cancer immunotherapy.By specifically targeting two different antigens,bs Abs reduce the distance between tumor and immune cells,thereby enhancing tumor killing directly.There are several mechanisms of action upon which bs Abs have been exploited.Accumulating experience on checkpoint-based therapy has promoted the clinical transformation of bs Abs targeting immunomodulatory checkpoints.Cadonilimab(PD-1×CTLA-4)is the first approved bs Ab targeting dual inhibitory checkpoints,which confirms the feasibility of bs Abs in immunotherapy.In this review we analyzed the mechanisms by which bs Abs targeting immunomodulatory checkpoints and their emerging applications in cancer immunotherapy.
基金supported by project grants from the National Natural Science Foundation of China(Nos.91859105,and 81961128025)the Program of Shanghai Academic Research Leader(No.19XD1420700)+1 种基金the Science and Technology Commission of Shanghai Municipality(No.20JC1418900)the Shanghai Municipal Key Clinical Specialty.
文摘Background:Intrahepatic cholangiocarcinoma(ICC)is a highly metastatic cancer.^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)enables sensitive tumor and metastasis detection.Our aim is to evaluate the influence of pre-treatment PET/CT on the N-and M-staging and subsequent clinical management in ICC patients.Methods:Between August 2010 and August 2018,660 consecutive ICC patients,without prior anti-tumor treatments nor other malignancies,were enrolled.The diagnostic performance of PET/CT on the N-and M-staging was compared with conventional imaging,and the preoperative staging accuracy and treatment re-allocation by PET/CT were retrospectively calculated.Survival difference was compared between patients receiving PET/CT or not after propensity score matching.Results:Patients were divided into group A(n=291)and group B(n=369)according to whether PET/CT was performed.Among 291 patients with both PET/CT and conventional imaging for staging in group A,PET/CT showed significantly higher sensitivity(83.0%vs.70.5%,P=0.001),specificity(88.3%vs.74.9%,P<0.001)and accuracy(86.3%vs.73.2%,P<0.001)than conventional imaging in diagnosing regional lymph node metastasis,as well as higher sensitivity(87.8%vs.67.6%,P<0.001)and accuracy(93.5%vs.89.3%,P=0.023)in diagnosing distant metastasis.Overall,PET/CT improved the accuracy of preoperative staging from 60.1%to 71.8%(P<0.001),and modified clinical treatment strategy in 5.8%(17/291)of ICC patients,with unique roles in different tumor-node-metastasis(TNM)stages.High tumor-to-non-tumor ratio(TNR)predicted poor overall survival[hazard ratio(HR)=2.17;95%confidence interval(CI):1.49-3.15;P<0.001].Furthermore,patients performing PET/CT had longer overall survival compared with those without PET/CT(HR=0.74;95%CI:0.58-0.93;P=0.011)after propensity score matching.Conclusions:PET/CT was valuable for diagnosing regional lymph node metastasis and distant metastasis in ICC patients,and facilitated accurate tumor staging and optimal treatment allocation.
