Background: Biliary mucinous cystic neoplasms(BMCNs) are rare hepatobiliary cystic tumors, which can be divided into noninvasive and invasive types. This study aimed to investigate the diagnosis, treatment, and progno...Background: Biliary mucinous cystic neoplasms(BMCNs) are rare hepatobiliary cystic tumors, which can be divided into noninvasive and invasive types. This study aimed to investigate the diagnosis, treatment, and prognosis of BMCNs in a large single center. Methods: We analyzed 49 patients with BMCNs confirmed by postoperative pathology at the First Afflliated Hospital, Zhejiang University School of Medicine between January 2007 and December 2021. Results: Among the 49 patients, 37 were female(75.5%), and the average age was 57.04 years. Common symptoms included abdominal discomfort, jaundice and fever, while 22 patients(44.9%) had no symptoms. Serum carbohydrate antigen(CA) 19-9 and CA125 concentrations were elevated in 34.8% and 19.6% of patients, respectively. Forty-eight patients had tumors in the intrahepatic bile ducts and only one had a tumor in the extrahepatic bile duct. Forty-eight patients with noninvasive intrahepatic BMCNs were further analyzed in terms of pathological features: 34(70.8%) had low-grade intraepithelial neoplasms(LGINs), and 14(29.2%) had high-grade intraepithelial neoplasms(HGINs). The potential immunohistochemical markers of BMCNs were cytokeratin(CK) 19, CK7, estrogen receptor and progesterone receptor. Follow-up data for 37 patients with intrahepatic BMCNs were obtained. The median overall survival(OS) of BMCNs was not reached. The longest survival time was 137 months.The 5-and 10-year OS rates were 100% and 85.4%, respectively. The 5-and 10-year recurrence-free survival(RFS) rates were 93.9% and 80.2%, respectively. Conclusions: BMCNs are rare cystic neoplasms that commonly occur in middle-aged females. BMCNs can only be diagnosed and classified by postoperative pathology, as there are no specific clinical presentations, serological indicators or imaging modalities for preoperative diagnosis. Complete surgical resection is necessary for BMCNs, and the postoperative prognosis is favorable.展开更多
To the Editor:Hepatocellular carcinoma(HCC)is one of the main causes of cancer related death worldwide,and new cases are expected to continue to increase in future[1].Surgical resection is still the best way to remove...To the Editor:Hepatocellular carcinoma(HCC)is one of the main causes of cancer related death worldwide,and new cases are expected to continue to increase in future[1].Surgical resection is still the best way to remove the tumor and improve patient’s prognosis.However,resection of caudate lobe often presents a technical challenge,even to accomplished hepatic surgeons.Caudate lobe is located anterior to the inferior vena cava(IVC)and posterior to the bifurcation of the portal vein(PV),generally consists of three regions:the paracaval portion,the left Spiegel lobe and the process portion[2].The anatomy of the paracaval portion includes the liver parenchyma ventral to the hepatic IVC and the area between the Spiegel lobe and the right lobe adjacent to the middle hepatic vein(MHV)ventrally,which was classified by Couinaud as segment IX[3].Here,we presented a case of HCC with successful downstaging therapy,as well as variation of MHV,which provides a safe path for anterior transection of segment IX.展开更多
To the Editor:We read with great interest the article by Schulze et al.entitled“Robotic surgery and liver transplantation:A single-center experience of 501 robotic donor hepatectomies”[1].It is the first single-cent...To the Editor:We read with great interest the article by Schulze et al.entitled“Robotic surgery and liver transplantation:A single-center experience of 501 robotic donor hepatectomies”[1].It is the first single-center report including over 500 fully robotic donor hepatectomies.For the donors,the overall complication rate was 6.4%(n=32).Postoperative self-limiting bleeding(0.4%)and bile leakage from the resection plane(1.8%)were rare.展开更多
Background:Liver transplantation(LT)is an effective treatment option for end-stage liver disease.Mammalian target of rapamycin(m TOR)inhibitors,such as rapamycin,are widely used post LT.Data sources:In this review,we ...Background:Liver transplantation(LT)is an effective treatment option for end-stage liver disease.Mammalian target of rapamycin(m TOR)inhibitors,such as rapamycin,are widely used post LT.Data sources:In this review,we focused on the anti-cancer activities and metabolic side effects of rapamycin after LT.The literature available on Pub Med for the period of January 1999-September 2022 was reviewed.The key words were rapamycin,sirolimus,liver transplantation,hepatocellular carcinoma,diabetes,and lipid metabolism disorder.Results:Rapamycin has shown excellent effects and is safer than other immunosuppressive regimens.It has exhibited excellent anti-cancer activity and has the potential in preventing hepatocellular carcinoma(HCC)recurrence post LT.Rapamycin is closely related to two long-term complications after LT,diabetes and lipid metabolism disorders.Conclusions:Rapamycin prevents HCC recurrence post LT in some patients,but it also induces metabolic disorders.Reasonable use of rapamycin benefits the liver recipients.展开更多
Dawei was in intensive care unit on a ventilator.He was declared brain death after a traffic accident.At visiting time,his younger brother Dayong told me their final decision to give up the subsequent treatment.“We ...Dawei was in intensive care unit on a ventilator.He was declared brain death after a traffic accident.At visiting time,his younger brother Dayong told me their final decision to give up the subsequent treatment.“We don’t have enough money and medical insurance,we can’t afford further treatment”,he said.展开更多
Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020.It includes hepatocellular carcinoma(HCC)(representing 75%-85%of cases),intrahepatic ...Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020.It includes hepatocellular carcinoma(HCC)(representing 75%-85%of cases),intrahepatic cholangiocarcinoma(representing 10%-15%of cases),and other rare types.The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years;however,high tumor recurrence rates continue to limit long-term survival,even after radical surgical resection(exceeding 50%recurrence).For resectable recurrent liver cancer,surgical removal[either salvage liver transplantation(SLT)or repeat hepatic resection]remains the most effective therapy that is potentially curative for recurrent HCC.Thus,here,we introduce surgical treatment for recurrent HCC.Areas Covered:A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022.Expert commentary:In general,long-term survival after the reresection of recurrent liver cancer is usually beneficial.SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients;however,SLT is constrained by the supply of liver grafts.SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival.When considering the similar overall survival rate and the current situation of donor shortages,repeat liver resection remains an important option for recurrent HCC.展开更多
Background:Liver transplantation(LT)is the best treatment for patients with hepatocellular carcinoma(HCC).However,the surgical technique needs to be improved.The present study aimed to evaluate the“no-touch”techniqu...Background:Liver transplantation(LT)is the best treatment for patients with hepatocellular carcinoma(HCC).However,the surgical technique needs to be improved.The present study aimed to evaluate the“no-touch”technique in LT.Methods:From January 2018 to December 2019,we performed a prospective randomized controlled trial on HCC patients who underwent LT.The patients were randomized into two groups:a no-touch technique LT group(NT group,n=38)and a conventional LT technique group(CT group,n=46).Operative outcomes and survival in the two groups were analyzed.Results:The perioperative parameters were comparable between the two groups(P>0.05).There was no significant difference between the two groups in disease-free survival(DFS)(P=0.732)or overall survival(OS)(P=0.891).Of 36 patients who were beyond the Hangzhou criteria for LT,the DFS of the patients in the NT group was significantly longer than that in the CT group(median 402 vs.126 days,P=0.025).In 31 patients who had portal vein tumor thrombosis(PVTT),DFS and OS in the NT group were significantly better than those in the CT group(median DFS 420 vs.167 days,P=0.022;2-year OS rate 93.8%vs.66.7%,P=0.043).In 14 patients who had diffuse-type HCCs,DFS and OS were significantly better in the NT group than those in the CT group(median DFS 141 vs.56 days,P=0.008;2-year OS rate 75.0%vs.33.3%,P=0.034).Multivariate analysis showed that for patients with PVTT and diffusetype HCCs,the no-touch technique was an independent favorable factor for OS(PVTT:HR=0.018,95%CI:0.001-0.408,P=0.012;diffuse-type HCCs:HR=0.034,95%CI:0.002-0.634,P=0.024).Conclusions:The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique.The no-touch technique may provide a new and effective LT technique for advanced HCCs.展开更多
Background:Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past.But it has seemed to remain controversial in the last decade,as a result of modified c...Background:Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past.But it has seemed to remain controversial in the last decade,as a result of modified clinical protocols,selected recipients,and advanced technology of organ perfusion and preservation.The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death(DCD).Methods:A total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups:using graft from older donor(aged≥65 years,n=87)and younger donor(age<65 years,n=857).Propensity score matching(PSM)was applied to eliminate selection bias.Results:A progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68%to 15.44%during the study period.The well-balanced older donor(n=79)and younger donor(n=79)were 1:1 matched.There were significantly more episodes of biliary nonanastomotic stricture(NAS)in the older donor group than the younger donor group[15/79(19.0%)vs.6/79(7.6%);P=0.017].The difference did not reach statistical significance regarding early allograft dysfunction(EAD)and primary non-function(PNF).Older livers had a trend toward inferior 1-,2-,3-year graft and overall survival compared with younger livers,but these differences were not statistically significant(63.1%,57.6%,57.6%vs.76.9%,70.2%,67.7%,P=0.112;64.4%,58.6%,58.6%vs.76.9%,72.2%,72.2%,P=0.064).The only risk factor for poor survival was ABO incompatible transplant(P=0.008)in the older donor group.In the subgroup of ABO incompatible cases,it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group[6/8(75.0%)vs.3/14(21.4%);P=0.014].Conclusions:Transplants with grafts from older donors(aged≥65 years)after circulatory death are more frequently associated with inferior outcome compared to those from younger donors.Older grafts from DCD are more likely to develop NAS,especially in ABO incompatible cases.展开更多
Background:Wernicke encephalopathy(WE)is an acute neurological disease resulting from vitamin B1 deficiency,and there are only very few case reports of WE after liver transplantation.The present study aimed to investi...Background:Wernicke encephalopathy(WE)is an acute neurological disease resulting from vitamin B1 deficiency,and there are only very few case reports of WE after liver transplantation.The present study aimed to investigate the clinical characteristics,etiology,magnetic resonance imaging(MRI)features,treatment and prognosis of patients with WE after liver transplantation.Methods:Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital,Zhejiang University School of Medicine and Jiangxi Provincial People’s Hospital between January 2011 and December 2021 were retrospectively analyzed.Results:Among the 23 patients diagnosed with WE after liver transplantation,6(26%)had a classic triad of impaired consciousness,oculomotor palsy and ataxia,and 17(74%)had two features.The misdiagno-sis rate was 65%.After treatment with high-dose vitamin B1,19(83%)patients showed improvement,whereas 4(17%)showed no improvement,including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia.Conclusions:The misdiagnosis rate is high in the early stage of WE,and the prognosis is closely asso-ciated with whether WE is diagnosed early and treated timely.High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment.Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation.展开更多
Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipi...Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. Results: Early posttransplant hypercholesterolemia(EPHC) was independently inversely associated with the risk of recurrence [hazard ratio(HR) = 0.630;P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC(B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence(HR = 0.504;P = 0.006) and mortality(HR = 0.511;P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival(89.6% and 83.7% vs. 83.8% and 72.7% respectively;P = 0.023), and 1-year and 3-year overall survival(95.8% and 84.8% vs. 94.6% and 77.6% respectively;P = 0.039). In the subgroup analysis, BEPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria;whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC(recurrence HR = 0.306, P = 0.011;mortality HR = 0.325, P = 0.031).Conclusions: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.展开更多
Background:Remote ischemic perconditioning(RIPerC)has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury(IRI).This study investigated the role of exosomes in RIPerC of liver grafts in rats.Me...Background:Remote ischemic perconditioning(RIPerC)has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury(IRI).This study investigated the role of exosomes in RIPerC of liver grafts in rats.Methods:Twenty-five rats(including 10 donors)were randomly divided into five groups(n=5 each group):five rats were used as sham-operated controls(Sham),ten rats were for orthotopic liver transplantation(OLT,5 donors and 5 recipients)and ten rats were for OLT+RIPerC(5 donors and 5 recipients).Liver architecture and function were evaluated.Results:Compared to the OLT group,the OLT+RIPerC group exhibited significantly improved liver graft histopathology and liver function(P<0.05).Furthermore,the number of exosomes and the level of P-Akt were increased in the OLT+RIPerC group.Conclusions:RIPerC effectively improves graft architecture and function,and this protective effect may be related to the increased number of exosomes.The upregulation of P-Akt may be involved in underlying mechanisms.展开更多
Pancreatic cancer is one of the most desperate malignances worldwide with approximately 470 0 0 0 deaths per year, and the 5-year survival rate is only 11% [1]. Pancreaticoduodenectomy(PD) is the standard treatment fo...Pancreatic cancer is one of the most desperate malignances worldwide with approximately 470 0 0 0 deaths per year, and the 5-year survival rate is only 11% [1]. Pancreaticoduodenectomy(PD) is the standard treatment for pancreatic head and periampullary lesions [2]. PD is often either described as “standard PD” or “extended PD”(e.g., “PD with portal vein resection, additional organ resection or arterial resection”) [3].展开更多
Hepatic arterial reconstruction remains a critically challenging technique in liver transplantation,as efficient graft and patient survival are dependent on strong and continuous arterial blood supply to the donor liv...Hepatic arterial reconstruction remains a critically challenging technique in liver transplantation,as efficient graft and patient survival are dependent on strong and continuous arterial blood supply to the donor liver[1,2].Complex arterial reconstruction has been identified as a crucial risk factor for arterial thrombosis[1–5].Consequently,selecting the appropriate arterial reconstruction method to decrease hepatic artery thrombosis has garnered the attention of the surgical community.展开更多
There are more than 1000 microbial species living in the complex human intestine.The gut microbial community plays an important role in protecting the host against pathogenic microbes,modulating immunity,regulating me...There are more than 1000 microbial species living in the complex human intestine.The gut microbial community plays an important role in protecting the host against pathogenic microbes,modulating immunity,regulating metabolic processes,and is even regarded as an endocrine organ.However,traditional culture methods are very limited for identifying microbes.With the application of molecular biologic technology in the field of the intestinal microbiome,especially metagenomic sequencing of the next-generation sequencing technology,progress has been made in the study of the human intestinal microbiome.Metagenomics can be used to study intestinal microbiome diversity and dysbiosis,as well as its relationship to health and disease.Moreover,functional metagenomics can identify novel functional genes,microbial pathways,antibiotic resistance genes,functional dysbiosis of the intestinal microbiome,and determine interactions and co-evolution between microbiota and host,though there are still some limitations.Metatranscriptomics,metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome.This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects.The limitations of metagenomics to be overcome are also discussed.Metatranscriptomics,metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed.展开更多
Background: Hepatocellular carcinoma(HCC) is one of the most common malignancies in the world. Gut microbiota has been demonstrated to play a critical role in liver inflammation, chronic fibrosis, liver cirrhosis, and...Background: Hepatocellular carcinoma(HCC) is one of the most common malignancies in the world. Gut microbiota has been demonstrated to play a critical role in liver inflammation, chronic fibrosis, liver cirrhosis, and HCC development through the gut-liver axis. Data sources: Recently there have been several innovative studies investigating gut microbial dysbiosismediated enhancement of HCC through the gut-liver axis. Literatures from January 1998 to January 2018 were searched in the Pub Med database using the keywords "gut microbiota" and "hepatocellular carcinoma" or "liver cancer", and the results of experimental and clinical studies were analyzed. Results: Gut microbial dysbiosis accompanies the progression of alcoholic liver disease, non-alcoholic fatty liver disease and liver cirrhosis, and promotes HCC progression in an experimental mouse model. The immune system and key factors such as Toll-like receptor 4 are involved in the process. There is evidence for gut microbial dysbiosis in hepatitis virus-related HCC patients. Conclusions: Gut microbial dysbiosis is closely associated with hepatic inflammation disease and HCC through the gut-liver axis. With the enhanced understanding of the interactions between gut microbiota and liver through the gut-liver axis, new treatment strategies for HCC are being developed.展开更多
AIM： To investigate the role of nuclear factor kappa B （NF-κB） in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion （I/R）, and its effect on intercellular adhesion molecule-1 （ICAM-1） ...AIM： To investigate the role of nuclear factor kappa B （NF-κB） in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion （I/R）, and its effect on intercellular adhesion molecule-1 （ICAM-1） expression and neutrophil infiltration. METHODS： Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate （PDTC） treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery （SMA） occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid （BALF） protein were assayed. Serum IL-6, lung malondialdehyde （MDA） and myeloperoxidase （MPO） as well as the expression level of NF-κB and ICAM-1 were measured.RESULTS： Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group （P=0.001）. Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly （P〈 0.05） when compared to I/R group.CONCLUSION： The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB.展开更多
AIM:To investigate the anti-tumor function of ginsenoside Rg3 on hepatocellular carcinoma(HCC) in vitro and in vivo,and its mechanism.METHODS:Hep1-6 and HepG2 cells were treated by Rg3 in different concentrations(0,50...AIM:To investigate the anti-tumor function of ginsenoside Rg3 on hepatocellular carcinoma(HCC) in vitro and in vivo,and its mechanism.METHODS:Hep1-6 and HepG2 cells were treated by Rg3 in different concentrations(0,50,100 and 200 μg/mL) in vitro.After incubation for 0,6,12,24 and 48 h,cell viability was measured by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay.Apoptosis was identified by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labeling.Caspase-3 activity was measured by chromophore p-nitroanilide and flow cytometry.Bcl-2 family proteins were ascertained by Western-blotting.Mitochondria membrane potentialwas detected by 5,5',6' 6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide.Forty liver tumor-bearing C57Bl6 mice were divided randomly into 4 groups for intra-tumor injection of saline,ginsenoside Rg3,cyclophosphamide(CTX) and ginsenoside Rg3 + CTX combination.RESULTS:The survival time was followed up to 102 d.The mice in the Rg3 + CTX group showed significant increased survival time compared with those in the control group(P < 0.05).Rg3 could inhibit HCC cell proliferation and induce cell apoptosis in vitro in the concentration and time dependent manner.It also induced mitochondria membrane potential to decrease.Caspase-3 activation can be blocked by the inhibitor z-DEVD-FMK.Bax was up-regulated while Bcl-2 and Bcl-XL were down-regulated after Rg3 treatment.CONCLUSION:Our data suggested that Rg3 alone or combined with CTX inhibited tumor growth in vivo and prolonged mouse survival time by inducing HCC cell apoptosis via intrinsic pathway by expression alterations of Bcl-2 family proteins.展开更多
AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transp...AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (Delta psi m) and total nitric oxide (NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RTPCR) and western blotting, and peroxynitrite was semiquantified by western blotting of 3-nitrotyrosine. RESULTS Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P < 0.05). ROS (P < 0.001) including H2O2 (P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P < 0.05) reversed this trend. The collapse of Delta psi m induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P < 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P < 0.01). CONCLUSION Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up-regulation of the PI3K/Akt/eNOS/NO pathway.展开更多
OBJECTIVE: To explore the effect of two dominating signaling pathways, VEGF/KDR and angiopoietins/Tie2, on the formation of new blood vessel in hepatocellular carcinoma (HCC) growth and metastasis. METHODS: RT-PCR and...OBJECTIVE: To explore the effect of two dominating signaling pathways, VEGF/KDR and angiopoietins/Tie2, on the formation of new blood vessel in hepatocellular carcinoma (HCC) growth and metastasis. METHODS: RT-PCR and Western blot were employed to evaluate the VEGF/KDR and angiopoietins/Tie2 expression in samples from 23 patients with HCC. Meanwhile, microvessel density (MVD) was determined as a marker of angiogenesis by counting CD34 positive cells with the method of immunohistochemistry. RESULTS: The two pathways were activated in all HCC samples. The expressions of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2) were significantly higher (P<0.05) in hepatocellular carcinoma tissues and the margin of the tumor than those in control groups, and so did CD34 positive cells. Although significant difference in the expression of kinase insert domain containing receptor (KDR) and Ang1/Tie2 was not observed in all groups, their distinct high levels were seen in hepatoma and its margin compared with normal and cirrhotic liver. VEGF and Ang2 expressions were seen up-regulated in HCC with vascular invasion and satellite lesion. CONCLUSIONS: The two signaling pathways, VEGF/KDR and angiopoietins/Tie2 are activated in the process of angiogenesis in HCC and modulate the formation of new blood vessels. The imparity of the two signaling pathways' activation is to benefit HCC metastasis. In the two pathways, VEGF and Ang2 may play an important role in the process of angiogenesis, and are necessary indicators for the prognosis and metastasis of HCC. This study provides another clue for the exploration of anti-angiogenic agents.展开更多
Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and death.The develop...Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and death.The development of metabolic disease is closely related to the side effects of immunosuppressants.Therefore,optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic disease.The Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent studies.Emphasis is placed on the risk factors of metabolic diseases,the effect of immunosuppressants on metabolic disease,and the prevention and treatment of metabolic diseases.展开更多
基金supported by grants from Zhejiang Natural Science Foundation (GF21H030024)the General Scientific Re-search Project of Zhejiang Provincial Department of Education (Y202146219)the Postgraduate Education Research Project of Zhejiang University (20220326)。
文摘Background: Biliary mucinous cystic neoplasms(BMCNs) are rare hepatobiliary cystic tumors, which can be divided into noninvasive and invasive types. This study aimed to investigate the diagnosis, treatment, and prognosis of BMCNs in a large single center. Methods: We analyzed 49 patients with BMCNs confirmed by postoperative pathology at the First Afflliated Hospital, Zhejiang University School of Medicine between January 2007 and December 2021. Results: Among the 49 patients, 37 were female(75.5%), and the average age was 57.04 years. Common symptoms included abdominal discomfort, jaundice and fever, while 22 patients(44.9%) had no symptoms. Serum carbohydrate antigen(CA) 19-9 and CA125 concentrations were elevated in 34.8% and 19.6% of patients, respectively. Forty-eight patients had tumors in the intrahepatic bile ducts and only one had a tumor in the extrahepatic bile duct. Forty-eight patients with noninvasive intrahepatic BMCNs were further analyzed in terms of pathological features: 34(70.8%) had low-grade intraepithelial neoplasms(LGINs), and 14(29.2%) had high-grade intraepithelial neoplasms(HGINs). The potential immunohistochemical markers of BMCNs were cytokeratin(CK) 19, CK7, estrogen receptor and progesterone receptor. Follow-up data for 37 patients with intrahepatic BMCNs were obtained. The median overall survival(OS) of BMCNs was not reached. The longest survival time was 137 months.The 5-and 10-year OS rates were 100% and 85.4%, respectively. The 5-and 10-year recurrence-free survival(RFS) rates were 93.9% and 80.2%, respectively. Conclusions: BMCNs are rare cystic neoplasms that commonly occur in middle-aged females. BMCNs can only be diagnosed and classified by postoperative pathology, as there are no specific clinical presentations, serological indicators or imaging modalities for preoperative diagnosis. Complete surgical resection is necessary for BMCNs, and the postoperative prognosis is favorable.
基金the Natural Science Foundation of Zhejiang Province(LQ22H160058).
文摘To the Editor:Hepatocellular carcinoma(HCC)is one of the main causes of cancer related death worldwide,and new cases are expected to continue to increase in future[1].Surgical resection is still the best way to remove the tumor and improve patient’s prognosis.However,resection of caudate lobe often presents a technical challenge,even to accomplished hepatic surgeons.Caudate lobe is located anterior to the inferior vena cava(IVC)and posterior to the bifurcation of the portal vein(PV),generally consists of three regions:the paracaval portion,the left Spiegel lobe and the process portion[2].The anatomy of the paracaval portion includes the liver parenchyma ventral to the hepatic IVC and the area between the Spiegel lobe and the right lobe adjacent to the middle hepatic vein(MHV)ventrally,which was classified by Couinaud as segment IX[3].Here,we presented a case of HCC with successful downstaging therapy,as well as variation of MHV,which provides a safe path for anterior transection of segment IX.
文摘To the Editor:We read with great interest the article by Schulze et al.entitled“Robotic surgery and liver transplantation:A single-center experience of 501 robotic donor hepatectomies”[1].It is the first single-center report including over 500 fully robotic donor hepatectomies.For the donors,the overall complication rate was 6.4%(n=32).Postoperative self-limiting bleeding(0.4%)and bile leakage from the resection plane(1.8%)were rare.
基金supported by grants from the Key Program,National Natural Science Foundation of China(81930016)the National Key Research and Development Program of China(2021YFA1100500)+2 种基金the Major Research Plan of the National Natu-ral Science Foundation of China(92159202)Key Research&Devel-opment Plan of Zhejiang Province(2019C03050)The Construction Fund of Key Medical Disciplines of Hangzhou(OO20200093)。
文摘Background:Liver transplantation(LT)is an effective treatment option for end-stage liver disease.Mammalian target of rapamycin(m TOR)inhibitors,such as rapamycin,are widely used post LT.Data sources:In this review,we focused on the anti-cancer activities and metabolic side effects of rapamycin after LT.The literature available on Pub Med for the period of January 1999-September 2022 was reviewed.The key words were rapamycin,sirolimus,liver transplantation,hepatocellular carcinoma,diabetes,and lipid metabolism disorder.Results:Rapamycin has shown excellent effects and is safer than other immunosuppressive regimens.It has exhibited excellent anti-cancer activity and has the potential in preventing hepatocellular carcinoma(HCC)recurrence post LT.Rapamycin is closely related to two long-term complications after LT,diabetes and lipid metabolism disorders.Conclusions:Rapamycin prevents HCC recurrence post LT in some patients,but it also induces metabolic disorders.Reasonable use of rapamycin benefits the liver recipients.
基金supported by grants from the Zhejiang Natural Science Foundation(LQ20H030005)the Zhejiang Health Technology Project(2019RC153 and 2020KY126)。
文摘Dawei was in intensive care unit on a ventilator.He was declared brain death after a traffic accident.At visiting time,his younger brother Dayong told me their final decision to give up the subsequent treatment.“We don’t have enough money and medical insurance,we can’t afford further treatment”,he said.
基金Supported by the Jinan Microecological Biomedicine Shandong Laboratory,No. JNL-2022022Cthe Health Commission of Zhejiang Province,No. JBZX-202004
文摘Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020.It includes hepatocellular carcinoma(HCC)(representing 75%-85%of cases),intrahepatic cholangiocarcinoma(representing 10%-15%of cases),and other rare types.The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years;however,high tumor recurrence rates continue to limit long-term survival,even after radical surgical resection(exceeding 50%recurrence).For resectable recurrent liver cancer,surgical removal[either salvage liver transplantation(SLT)or repeat hepatic resection]remains the most effective therapy that is potentially curative for recurrent HCC.Thus,here,we introduce surgical treatment for recurrent HCC.Areas Covered:A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022.Expert commentary:In general,long-term survival after the reresection of recurrent liver cancer is usually beneficial.SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients;however,SLT is constrained by the supply of liver grafts.SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival.When considering the similar overall survival rate and the current situation of donor shortages,repeat liver resection remains an important option for recurrent HCC.
基金supported by grants from the National Key R&D Program of China(2017ZX10203205-005-004)Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022022C)Grant from Health Commission of Zhejiang Province(JBZX-202004)。
文摘Background:Liver transplantation(LT)is the best treatment for patients with hepatocellular carcinoma(HCC).However,the surgical technique needs to be improved.The present study aimed to evaluate the“no-touch”technique in LT.Methods:From January 2018 to December 2019,we performed a prospective randomized controlled trial on HCC patients who underwent LT.The patients were randomized into two groups:a no-touch technique LT group(NT group,n=38)and a conventional LT technique group(CT group,n=46).Operative outcomes and survival in the two groups were analyzed.Results:The perioperative parameters were comparable between the two groups(P>0.05).There was no significant difference between the two groups in disease-free survival(DFS)(P=0.732)or overall survival(OS)(P=0.891).Of 36 patients who were beyond the Hangzhou criteria for LT,the DFS of the patients in the NT group was significantly longer than that in the CT group(median 402 vs.126 days,P=0.025).In 31 patients who had portal vein tumor thrombosis(PVTT),DFS and OS in the NT group were significantly better than those in the CT group(median DFS 420 vs.167 days,P=0.022;2-year OS rate 93.8%vs.66.7%,P=0.043).In 14 patients who had diffuse-type HCCs,DFS and OS were significantly better in the NT group than those in the CT group(median DFS 141 vs.56 days,P=0.008;2-year OS rate 75.0%vs.33.3%,P=0.034).Multivariate analysis showed that for patients with PVTT and diffusetype HCCs,the no-touch technique was an independent favorable factor for OS(PVTT:HR=0.018,95%CI:0.001-0.408,P=0.012;diffuse-type HCCs:HR=0.034,95%CI:0.002-0.634,P=0.024).Conclusions:The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique.The no-touch technique may provide a new and effective LT technique for advanced HCCs.
基金the Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine(2013-0022).
文摘Background:Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past.But it has seemed to remain controversial in the last decade,as a result of modified clinical protocols,selected recipients,and advanced technology of organ perfusion and preservation.The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death(DCD).Methods:A total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups:using graft from older donor(aged≥65 years,n=87)and younger donor(age<65 years,n=857).Propensity score matching(PSM)was applied to eliminate selection bias.Results:A progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68%to 15.44%during the study period.The well-balanced older donor(n=79)and younger donor(n=79)were 1:1 matched.There were significantly more episodes of biliary nonanastomotic stricture(NAS)in the older donor group than the younger donor group[15/79(19.0%)vs.6/79(7.6%);P=0.017].The difference did not reach statistical significance regarding early allograft dysfunction(EAD)and primary non-function(PNF).Older livers had a trend toward inferior 1-,2-,3-year graft and overall survival compared with younger livers,but these differences were not statistically significant(63.1%,57.6%,57.6%vs.76.9%,70.2%,67.7%,P=0.112;64.4%,58.6%,58.6%vs.76.9%,72.2%,72.2%,P=0.064).The only risk factor for poor survival was ABO incompatible transplant(P=0.008)in the older donor group.In the subgroup of ABO incompatible cases,it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group[6/8(75.0%)vs.3/14(21.4%);P=0.014].Conclusions:Transplants with grafts from older donors(aged≥65 years)after circulatory death are more frequently associated with inferior outcome compared to those from younger donors.Older grafts from DCD are more likely to develop NAS,especially in ABO incompatible cases.
基金approved by Jiangxi Provincial People’s Hospital and First Affiliated Hospital,Zhejiang University School of Medicine(2022068 and 2022370).Written informed consent was obtained from all participants.
文摘Background:Wernicke encephalopathy(WE)is an acute neurological disease resulting from vitamin B1 deficiency,and there are only very few case reports of WE after liver transplantation.The present study aimed to investigate the clinical characteristics,etiology,magnetic resonance imaging(MRI)features,treatment and prognosis of patients with WE after liver transplantation.Methods:Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital,Zhejiang University School of Medicine and Jiangxi Provincial People’s Hospital between January 2011 and December 2021 were retrospectively analyzed.Results:Among the 23 patients diagnosed with WE after liver transplantation,6(26%)had a classic triad of impaired consciousness,oculomotor palsy and ataxia,and 17(74%)had two features.The misdiagno-sis rate was 65%.After treatment with high-dose vitamin B1,19(83%)patients showed improvement,whereas 4(17%)showed no improvement,including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia.Conclusions:The misdiagnosis rate is high in the early stage of WE,and the prognosis is closely asso-ciated with whether WE is diagnosed early and treated timely.High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment.Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation.
基金supported by grants from the National Natural Science Funds for Distinguished Young Scholars of China (81625003)the Key Program,National Natural Science Foundation of China (81930016)the Key Research&Development Plan of Zhejiang Province (2019C03050)。
文摘Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. Results: Early posttransplant hypercholesterolemia(EPHC) was independently inversely associated with the risk of recurrence [hazard ratio(HR) = 0.630;P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC(B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence(HR = 0.504;P = 0.006) and mortality(HR = 0.511;P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival(89.6% and 83.7% vs. 83.8% and 72.7% respectively;P = 0.023), and 1-year and 3-year overall survival(95.8% and 84.8% vs. 94.6% and 77.6% respectively;P = 0.039). In the subgroup analysis, BEPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria;whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC(recurrence HR = 0.306, P = 0.011;mortality HR = 0.325, P = 0.031).Conclusions: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.
基金This study was supported by the Public Projects of Zhe-jiang Province(LGF21H030006)the Major Science and Tech-nology Projects of Hainan province(ZDKJ2019009)+2 种基金Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022002A,JNL-2022023C)Research Unit Project of Chinese Academy of Medical Sciences(2019-I2M-5-030)Innovative Re-search Groups of National Natural Science Foundation of China(81721091).
文摘Background:Remote ischemic perconditioning(RIPerC)has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury(IRI).This study investigated the role of exosomes in RIPerC of liver grafts in rats.Methods:Twenty-five rats(including 10 donors)were randomly divided into five groups(n=5 each group):five rats were used as sham-operated controls(Sham),ten rats were for orthotopic liver transplantation(OLT,5 donors and 5 recipients)and ten rats were for OLT+RIPerC(5 donors and 5 recipients).Liver architecture and function were evaluated.Results:Compared to the OLT group,the OLT+RIPerC group exhibited significantly improved liver graft histopathology and liver function(P<0.05).Furthermore,the number of exosomes and the level of P-Akt were increased in the OLT+RIPerC group.Conclusions:RIPerC effectively improves graft architecture and function,and this protective effect may be related to the increased number of exosomes.The upregulation of P-Akt may be involved in underlying mechanisms.
基金supported by grants from the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (JNL-2022016B)the Natural Science Foundation of Zhejiang Province (Y21H160259)。
文摘Pancreatic cancer is one of the most desperate malignances worldwide with approximately 470 0 0 0 deaths per year, and the 5-year survival rate is only 11% [1]. Pancreaticoduodenectomy(PD) is the standard treatment for pancreatic head and periampullary lesions [2]. PD is often either described as “standard PD” or “extended PD”(e.g., “PD with portal vein resection, additional organ resection or arterial resection”) [3].
基金the Fundamental Research Funds for the Central Universities(2022ZFJH003)the Major Research Plan of the National Natural Science Foundation of China(92159202)+1 种基金the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022016B)Zhejiang Provincial Natural Science Foundation of China g(Y21H160259).
文摘Hepatic arterial reconstruction remains a critically challenging technique in liver transplantation,as efficient graft and patient survival are dependent on strong and continuous arterial blood supply to the donor liver[1,2].Complex arterial reconstruction has been identified as a crucial risk factor for arterial thrombosis[1–5].Consequently,selecting the appropriate arterial reconstruction method to decrease hepatic artery thrombosis has garnered the attention of the surgical community.
基金Supported by National Basic Research Program(973 Program)of China,No.2013CB531403
文摘There are more than 1000 microbial species living in the complex human intestine.The gut microbial community plays an important role in protecting the host against pathogenic microbes,modulating immunity,regulating metabolic processes,and is even regarded as an endocrine organ.However,traditional culture methods are very limited for identifying microbes.With the application of molecular biologic technology in the field of the intestinal microbiome,especially metagenomic sequencing of the next-generation sequencing technology,progress has been made in the study of the human intestinal microbiome.Metagenomics can be used to study intestinal microbiome diversity and dysbiosis,as well as its relationship to health and disease.Moreover,functional metagenomics can identify novel functional genes,microbial pathways,antibiotic resistance genes,functional dysbiosis of the intestinal microbiome,and determine interactions and co-evolution between microbiota and host,though there are still some limitations.Metatranscriptomics,metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome.This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects.The limitations of metagenomics to be overcome are also discussed.Metatranscriptomics,metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed.
基金supported by grants from the National Natural Science Foundation of China(81672422 and 81600506)Natural Science Foundation of Zhejiang Province(LY15H160033)+4 种基金Zhejiang Province Health Department Program(2014KYB081 and 2017KY322)Open Project in State Key Laboratory for Diagnosis and Treatment of Infectious Disease(2015KF03)Academician JieShou Li Intestinal Mucosal Barrier Fund(201208)Medical S&T Project of Zhejiang Province(201479797)National S&T Major Project of China(2018ZX10301201)
文摘Background: Hepatocellular carcinoma(HCC) is one of the most common malignancies in the world. Gut microbiota has been demonstrated to play a critical role in liver inflammation, chronic fibrosis, liver cirrhosis, and HCC development through the gut-liver axis. Data sources: Recently there have been several innovative studies investigating gut microbial dysbiosismediated enhancement of HCC through the gut-liver axis. Literatures from January 1998 to January 2018 were searched in the Pub Med database using the keywords "gut microbiota" and "hepatocellular carcinoma" or "liver cancer", and the results of experimental and clinical studies were analyzed. Results: Gut microbial dysbiosis accompanies the progression of alcoholic liver disease, non-alcoholic fatty liver disease and liver cirrhosis, and promotes HCC progression in an experimental mouse model. The immune system and key factors such as Toll-like receptor 4 are involved in the process. There is evidence for gut microbial dysbiosis in hepatitis virus-related HCC patients. Conclusions: Gut microbial dysbiosis is closely associated with hepatic inflammation disease and HCC through the gut-liver axis. With the enhanced understanding of the interactions between gut microbiota and liver through the gut-liver axis, new treatment strategies for HCC are being developed.
基金Supported by The Natural Science Foundation of Liaoning Province,No.20042135
文摘AIM： To investigate the role of nuclear factor kappa B （NF-κB） in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion （I/R）, and its effect on intercellular adhesion molecule-1 （ICAM-1） expression and neutrophil infiltration. METHODS： Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate （PDTC） treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery （SMA） occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid （BALF） protein were assayed. Serum IL-6, lung malondialdehyde （MDA） and myeloperoxidase （MPO） as well as the expression level of NF-κB and ICAM-1 were measured.RESULTS： Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group （P=0.001）. Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly （P〈 0.05） when compared to I/R group.CONCLUSION： The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB.
基金Supported by The National Natural Science Foundation of China,No.30700778the Health Bureau Fund of Zhejiang Province,No.2007QN006,No.2008B080 and No.2008A050National Basic Research Program(973)of China,No.2007CB513005
文摘AIM:To investigate the anti-tumor function of ginsenoside Rg3 on hepatocellular carcinoma(HCC) in vitro and in vivo,and its mechanism.METHODS:Hep1-6 and HepG2 cells were treated by Rg3 in different concentrations(0,50,100 and 200 μg/mL) in vitro.After incubation for 0,6,12,24 and 48 h,cell viability was measured by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay.Apoptosis was identified by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labeling.Caspase-3 activity was measured by chromophore p-nitroanilide and flow cytometry.Bcl-2 family proteins were ascertained by Western-blotting.Mitochondria membrane potentialwas detected by 5,5',6' 6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide.Forty liver tumor-bearing C57Bl6 mice were divided randomly into 4 groups for intra-tumor injection of saline,ginsenoside Rg3,cyclophosphamide(CTX) and ginsenoside Rg3 + CTX combination.RESULTS:The survival time was followed up to 102 d.The mice in the Rg3 + CTX group showed significant increased survival time compared with those in the control group(P < 0.05).Rg3 could inhibit HCC cell proliferation and induce cell apoptosis in vitro in the concentration and time dependent manner.It also induced mitochondria membrane potential to decrease.Caspase-3 activation can be blocked by the inhibitor z-DEVD-FMK.Bax was up-regulated while Bcl-2 and Bcl-XL were down-regulated after Rg3 treatment.CONCLUSION:Our data suggested that Rg3 alone or combined with CTX inhibited tumor growth in vivo and prolonged mouse survival time by inducing HCC cell apoptosis via intrinsic pathway by expression alterations of Bcl-2 family proteins.
基金Supported by National Natural Science Foundation of China,No.81421062the Science and Technology Bureau of Zhejiang Province,China,No.2016C33145+1 种基金the National Natural Science Foundation of China,No.81470891the 863 National High Technology Research and Development Program of China for young scientist No.2015AA020923
文摘AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (Delta psi m) and total nitric oxide (NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RTPCR) and western blotting, and peroxynitrite was semiquantified by western blotting of 3-nitrotyrosine. RESULTS Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P < 0.05). ROS (P < 0.001) including H2O2 (P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P < 0.05) reversed this trend. The collapse of Delta psi m induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P < 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P < 0.01). CONCLUSION Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up-regulation of the PI3K/Akt/eNOS/NO pathway.
文摘OBJECTIVE: To explore the effect of two dominating signaling pathways, VEGF/KDR and angiopoietins/Tie2, on the formation of new blood vessel in hepatocellular carcinoma (HCC) growth and metastasis. METHODS: RT-PCR and Western blot were employed to evaluate the VEGF/KDR and angiopoietins/Tie2 expression in samples from 23 patients with HCC. Meanwhile, microvessel density (MVD) was determined as a marker of angiogenesis by counting CD34 positive cells with the method of immunohistochemistry. RESULTS: The two pathways were activated in all HCC samples. The expressions of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2) were significantly higher (P<0.05) in hepatocellular carcinoma tissues and the margin of the tumor than those in control groups, and so did CD34 positive cells. Although significant difference in the expression of kinase insert domain containing receptor (KDR) and Ang1/Tie2 was not observed in all groups, their distinct high levels were seen in hepatoma and its margin compared with normal and cirrhotic liver. VEGF and Ang2 expressions were seen up-regulated in HCC with vascular invasion and satellite lesion. CONCLUSIONS: The two signaling pathways, VEGF/KDR and angiopoietins/Tie2 are activated in the process of angiogenesis in HCC and modulate the formation of new blood vessels. The imparity of the two signaling pathways' activation is to benefit HCC metastasis. In the two pathways, VEGF and Ang2 may play an important role in the process of angiogenesis, and are necessary indicators for the prognosis and metastasis of HCC. This study provides another clue for the exploration of anti-angiogenic agents.
基金National Science and Technology Major Project of China,No.2017ZX10203205National Natural Science Funds for Distinguished Young Scholar of China,No.81625003National Natural Science Foundation of China,No.81930016.
文摘Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and death.The development of metabolic disease is closely related to the side effects of immunosuppressants.Therefore,optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic disease.The Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent studies.Emphasis is placed on the risk factors of metabolic diseases,the effect of immunosuppressants on metabolic disease,and the prevention and treatment of metabolic diseases.
