Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunot...Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines.In spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.展开更多
The initiation and progression of liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, are dependent on its tumor microenvironment. Immune cells are key players in the liver cancer mic...The initiation and progression of liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, are dependent on its tumor microenvironment. Immune cells are key players in the liver cancer microenvironment and show complicated crosstalk with cancer cells. Emerging evidence has shown that the functions of immune cells are closely related to cell metabolism. However, the effects of metabolic changes of immune cells on liver cancer progression are largely undefined. In this review, we summarize the recent findings of immunometabolism and relate these findings to liver cancer progression. We also explore the translation of the understanding of immunometabolism for clinical use.展开更多
BACKGROUND Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide.Socioeconomic development,indicated by the Human Development Index(HDI),is closely interconnec...BACKGROUND Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide.Socioeconomic development,indicated by the Human Development Index(HDI),is closely interconnected with public health.But the manner in which social development and medical advances influenced liver cancer patients in the past decade is still unknown.AIM To investigate the influence of HDI on clinical outcomes for patients with existing liver cancer from 2008 to 2018.METHODS The HDI values were obtained from the United Nations Development Programme,the age-standardized incidence and mortality rates of liver cancer were obtained from the GLOBOCAN database to calculate the mortality-toincidence ratio,and the estimated 5-year net survival of patients with liver cancer was provided by the CONCORD-3 program.We then explored the association of mortality-to-incidence ratio and survival with HDI,with a focus on geographic variability across countries as well as temporal heterogeneity over the past decade.RESULTS From 2008 to 2018,the epidemiology of liver cancer had changed across countries.Liver cancer mortality-to-incidence ratios were negatively correlated and showed good fit with a modified“dose-to-inhibition response”pattern with HDI(r=-0.548,P<0.0001 for 2018;r=-0.617,P<0.0001 for 2008).Cancer survival was positively associated with HDI(r=0.408,P<0.01)and negatively associated with mortality-to-incidence ratio(r=-0.346,P<0.05),solidly confirming the interrelation among liver cancer outcome indicators and socioeconomic factors.Notably,in the past decade,the HDI values in most countries have increased alongside a decreasing tendency of liver cancer mortality-to-incidence ratios(P<0.0001),and survival outcomes have simultaneously improved(P<0.001),with significant disparities across countries.CONCLUSION Socioeconomic factors have a significant influence on cancer outcomes.HDI values have increased along with improved cancer outcomes,with significant disparities among countries.展开更多
Background: The enhanced recovery after surgery (ERAS) protocol is an evidence-based perioperative care program aimed at reducing surgical stress response and accelerating recovery. However, a small propor- tion of pa...Background: The enhanced recovery after surgery (ERAS) protocol is an evidence-based perioperative care program aimed at reducing surgical stress response and accelerating recovery. However, a small propor- tion of patients fail to bene t from the ERAS program following pancreaticoduodenectomy. This study aimed to identify the risk factors associated with failure of ERAS program in pancreaticoduodenectomy. Methods: Between May 2014 and December 2017, 176 patients were managed with ERAS program fol-lowing pancreaticoduodenectomy. ERAS failure was indicated by prolonged hospital stay, unplanned read- mission or unplanned reoperation. Demographics, postoperative recovery and compliance were compared of those ERAS failure groups to the ERAS success group. Results: ERAS failure occurred in 59 patients, 33 of whom had prolonged hospital stay, 18 were readmitted to hospital within 30 days after discharge, and 8 accepted reoperation. Preoperative American Society of Anesthesiologists (ASA) score of ≥III (OR = 2.736;95% CI: 1.276 6.939;P=0.028) and albumin (ALB) level of <35g/L (OR=3.589;95% CI: 1.403 9.181;P=0.008) were independent risk factors associated with prolonged hospital stay. Elderly patients (>70 years) were on a high risk of unplanned reoperation (62.5% vs. 23.1%, P=0.026). Patients with prolonged hospital stay and unplanned reoperation had delayed intake and increased intolerance of oral foods. Prolonged stay patients got off bed later than ERAS success patients did (65h vs. 46h, P =0.012). Unplanned reoperation patients tended to experience severer pain than ERAS success patients did (3 score vs. 2 score, P =0.035). Conclusions: Patients with high ASA score, low ALB level or age >70 years were at high risk of ERAS failure in pancreaticoduodenectomy. These preoperative demographic and clinical characteristics are important determinants to obtain successful postoperative recovery in ERAS program.展开更多
AIM:To identify the role of human development in the incidence and mortality rates of gastrointestinal cancers worldwide.METHODS:The age-standardized incidence and mortality rates for gastrointestinal cancers,includin...AIM:To identify the role of human development in the incidence and mortality rates of gastrointestinal cancers worldwide.METHODS:The age-standardized incidence and mortality rates for gastrointestinal cancers,including cancers of the esophagus,stomach,pancreas,liver,gallbladder,and colorectum,were obtained from the GLOBOCAN 2008 database and United States Cancer Statistics(USCS)report.The human development index(HDI)data were calculated according to the 2011 Human Development Report.We estimated the mortality-toincidence ratios(MIRs)at the regional and national levels,and explored the association of the MIR with development levels as measured by the HDI using a modified"drug dose to inhibition response"model.Furthermore,countries were divided into four groups according to the HDI distribution,and the MIRs of the four HDI groups were compared by one-way ANOVA followed by the Tukey-Kramer post-hoc test.Statespecific MIRs in the United States were predicted from the estimated HDI using the fitted non-linear model,and were compared with the actual MIRs calculated from data in the USCS report.RESULTS:The worldwide incidence and mortality rates of gastrointestinal cancers were as high as 39.4and 54.9 cases per 100000 individuals,respectively.Linear and non-linear regression analyses revealed an inverse correlation between the MIR of gastrointestinal cancers and the HDI at the regional and national levels(<0;P=0.0028 for regional level and<0.0001 for national level,ANOVA).The MIR differed significantly among the four HDI areas(very high HDI,0.620±0.033;high HDI,0.807±0.018;medium HDI,0.857±0.021;low HDI,0.953±0.011;P<0.001,oneway ANOVA).Prediction of the MIRs for individual United States states using best-fitted non-linear models showed little deviation from the actual MIRs in the United States.Except for 28 data points(9.93%of282),the actual MIRs of all gastrointestinal cancers were mostly located in the prediction intervals via the best-fit non-linear regression models.CONCLUSION:The inverse correlation between HDI and MIR demonstrates that more developed areas have a relatively efficacious healthcare system,resulting in low MIRs,and HDI can be used to estimate the MIR.展开更多
Objective: To sum up the experience in liver trans- plantation in a period of ten years at a single center. Methods: We retrospectively reviewed the clinical re- cords of 120 patients receiving liver transplantation f...Objective: To sum up the experience in liver trans- plantation in a period of ten years at a single center. Methods: We retrospectively reviewed the clinical re- cords of 120 patients receiving liver transplantation from April 1993 to October 2002. The patients' cli- nical characteristics, surgical techniques, complica- tions and survival were compared in the phases of 1993-1997 (phase Ⅰ), 1999 (phase Ⅱ), and 2000- 2002 (phase Ⅲ). Results: Malignant liver diseases were major indica- tions for liver transplantation in phase Ⅰ(100%) and Ⅱ(53. 3%), but decreased markedly in percentage in phase Ⅲ(34. 0%). When compared with recipi- ents in phase Ⅰ and Ⅱ, the survival of recipients with benign liver diseases in phase Ⅲ was significantly im- proved with the 3-month, 6-month and 1-year sur- vival rates of 85. 7%, 84. 5% and 83. 1%, respec- tively. For patients with malignant liver diseases, the 3-month, 6-month and 1-year survival rates were 87. 4%, 81. 1% and 46. 0%, respectively. The rein- fection rate of hepatitis B virus was 24% 12 months after transplantation. With technical refinements, the incidence of postransplantation vascular compli- cations has significantly decreased from 29. 4% in phase Ⅰ and Ⅱ to 4. 9% in phase Ⅲ. Biliary compli- cations remained one of the major obstacles to long- term survival. No reno-venous bypass was applied in phase Ⅲ, providing a promising outcome. Conclusion: Strict selection of potential recipients, technical refinement, appropriate management of vascular and biliary complications, and prophylaxis of recurrences of hepatitis B and malignant liver dis- eases are important to obtain long-term survival of patients receiving liver transplantation in China.展开更多
BACKGROUND Surgical site infections (SSI) remain a major cause of morbidity after hepatectomy for hepatocellular carcinoma (HCC).AIM To identify the risk factors associated with SSI,and develop a nomogram to predict S...BACKGROUND Surgical site infections (SSI) remain a major cause of morbidity after hepatectomy for hepatocellular carcinoma (HCC).AIM To identify the risk factors associated with SSI,and develop a nomogram to predict SSI among patients undergoing hepatectomy.METHODS We retrospectively reviewed the data of patients diagnosed with HCC undergoing hepatectomy at two academic institutions in China,and evaluated the occurrence of SSI.Independent risk factors for SSI were identified using univariate and multivariate analyses.Based on these independent risk factors,a nomogram was established using the data of patients in the first institution,and was validated using data from an external independent cohort from the second institution.RESULTS The nomogram was established using data from 309 patients,whereas the validation cohort used data from 331 patients.The operation duration,serum albumin level,repeat hepatectomy,and ASA score were identified as independent risk factors.The concordance index (C-index) of the nomogram for SSI prediction in the training cohort was 0.86;this nomogram also performed well in the external validation cohort,with a C-index of 0.84.Accordingly,we stratified patients into three groups,with a distinct risk range based on the nomogram prediction,to guide clinical practice.CONCLUSION Our novel nomogram offers good preoperative prediction for SSIs in patients undergoing hepatectomy.展开更多
Sister Mary Joseph's nodule(SMJN) refers to a metastatic tumor of the umbilicus.It is a rare entity which arises from a malignancy in the intra-abdominal cavity.We herein describe a patient who presented with SMJN...Sister Mary Joseph's nodule(SMJN) refers to a metastatic tumor of the umbilicus.It is a rare entity which arises from a malignancy in the intra-abdominal cavity.We herein describe a patient who presented with SMJN as his first sign of pancreatic cancer.It is an even more unusual case of SMJN.We therefore,suggest that pancreatic cancer should be included in the differential diagnosis when an umbilical mass is found.With the progress made in surgical procedures and other modalities,an early diagnosis will dramatically improve the prognosis of the patients.展开更多
OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation. METHODS: Reverse transcription-polymerase chain rea...OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in PBMCs from 22 patients receiving liver transplantation, 13 patients with primary liver carcinoma (PLC), and 12 healthy controls. To determine whether 4-1BB molecule is also expressed on the surface of CD4^+ and CD8^+ T cell, flow cytometry was used to analyse the phenotype of T cell subsets from the blood of liver transplantation patients. RESULTS: 4-1BB mRNA was detected in PBMCs from stable survivors after liver transplantation, but almost not deteeted in PBMCs from PLC patients and healthy controls. Meanwhile, 4-1BB was almost not expressed on the surface of CD4^+ and CD8^+ T cells in healthy controls and PLC patients. A low level of 4-1BB expression, however, was found on the surface of CD4^+ and CD8^+ T cells from the stable survivors after liver transplantation. CONCLUSIONS: This study demonstrates that although patients are stable after liver transplantation, effector T-cells can also be activated through the signal of 4-1BB molecule and persistent irmmune response to grafts. Blockage of 4-1BB/4-1BBL pathway may benefitially reduce the clinical dosage of immunosuppressive agents and prolong the survival of grafts.展开更多
Budd-Chiari syndrome(BCS)is defined as hepatic venous outflow obstruction at any level from the small hepatic veins to the junction of the inferior vena cava(IVC)and the right atrium,regardless of the cause of obstruc...Budd-Chiari syndrome(BCS)is defined as hepatic venous outflow obstruction at any level from the small hepatic veins to the junction of the inferior vena cava(IVC)and the right atrium,regardless of the cause of obstruction.We present two cases of acute iatrogenic BCS and our clinical management of these cases.The first case was a 43-year-old woman who developed acute BCS following the implantation of an IVC stent for the correction of stenosis in the IVC after hepatectomy for hepatolithiasis.The second case was a61-year-old woman with complete obstruction of the outflow of hepatic veins during bilateral hepatectomy for hepatolithiasis.Acute iatrogenic BCS should be con-sidered a rare complication following hepatectomy for hepatolithiasis.Awareness of potential hepatic outflow obstructions and timely management are critical to avoid poor outcomes when performing hepatectomy for hepatolithiasis.展开更多
Objective: To sum up the preliminary experience in living related liver transplantation (LRLT). Methods: A 9-month-old male infant with biliary atresia (BA) who had undergone an unsuccessful Kasai operation was define...Objective: To sum up the preliminary experience in living related liver transplantation (LRLT). Methods: A 9-month-old male infant with biliary atresia (BA) who had undergone an unsuccessful Kasai operation was defined as a candidate for LR- LT. The donor was his 30-year-old mother. Her la- teral lobe of the left liver was transplanted into the infant's body as the graft. The left branches of the portal vein, left hepatic artery and left hepatic vein of the graft were end-to-end anastomosed to the por- tal vein, hepatic artery proper and hepatic vein of the recipient respectively. Biliary drainage was re- established via Roux-en-Y operation. Results: The donor retained her liver function within 2 weeks after the operation. Steroid and FK506 were prescribed in immunosuppressive therapy for the re- cipient. The blood bilirubin level of the infant de- creased to normal 2 weeks after operation. No acute rejection occurred. Biliary leakage in the early peri- od after the transplantation was controlled by drain- age, and E. coli infection was effectively treated with antibiotics. The donor and recipient are in satisfacto- ry condition to the present. Conclusion: LRLT is advisable for children with bili- ary atresia.展开更多
Hepatocellular carcinoma(HCC)is characterized by high heterogeneity in both intratumoral and interpatient manners.While interpatient heterogeneity is related to personalized therapy,intratumoral heterogeneity(ITH)larg...Hepatocellular carcinoma(HCC)is characterized by high heterogeneity in both intratumoral and interpatient manners.While interpatient heterogeneity is related to personalized therapy,intratumoral heterogeneity(ITH)largely influences the efficacy of therapies in individuals.ITH contributes to tumor growth,metastasis,recurrence,and drug resistance and consequently limits the prognosis of patients with HCC.There is an urgent need to understand the causes,characteristics,and consequences of tumor heterogeneity in HCC for the purposes of guiding clinical practice and improving survival.Here,we summarize the studies and technologies that describe ITH in HCC to gain insight into the origin and evolutionary process of heterogeneity.In parallel,evidence is collected to delineate the dynamic relationship between ITH and the tumor ecosystem.We suggest that conducting comprehensive studies of ITH using single-cell approaches in temporal and spatial dimensions,combined with population-based clinical trials,will help to clarify the clinical implications of ITH,develop novel intervention strategies,and improve patient prognosis.展开更多
To the Editor:Liver transplantation remains the only cure for end-stage liver disease.Tacrolimus is widely used as a first-line immunosuppressive drug to prevent organ rejection after liver transplantation[1–3].Howev...To the Editor:Liver transplantation remains the only cure for end-stage liver disease.Tacrolimus is widely used as a first-line immunosuppressive drug to prevent organ rejection after liver transplantation[1–3].However,tacrolimus has a narrow therapeutic index and wide inter-individual variability in pharmacokinetics,which can result in underimmunosuppression or toxicity.Orally administered tacrolimus is rapidly absorbed from the distal gastrointestinal tract and extensively metabolized in the liver and intestinal walls by cytochrome P450(CYP)3A4 and 3A5[2,4,5].展开更多
BACKGROUND For tumors in the neck and body of the pancreas,distal pancreatectomy(DP)has been the standard surgical procedure for the last few decades and central pancreatectomy(CP)is an alternative surgical option.Whe...BACKGROUND For tumors in the neck and body of the pancreas,distal pancreatectomy(DP)has been the standard surgical procedure for the last few decades and central pancreatectomy(CP)is an alternative surgical option.Whether CP better preserves remnant pancreatic endocrine and exocrine functions after surgery remains a subject of debate.AIM To evaluate the safety and efficacy of CP compared with DP for benign or lowgrade malignant pancreatic tumors in the neck and body of the pancreas.METHODS This retrospective study enrolled 296 patients who underwent CP or DP for benign and low-malignant neoplasms at the same hospital between January 2016 and March 2020.Perioperative outcomes and long-term morbidity of endocrine/exocrine function were prospectively evaluated.RESULTS No significant difference was observed in overall morbidity or clinically relevant postoperative pancreatic fistula between the two groups(P=0.055).Delayed gastric emptying occurred more frequently in the CP group than in the DP group(29.4%vs 15.3%;P<0.005).None of the patients in the CP group had new-onset or aggravated distal metastasis,whereas 40 patients in the DP group had endocrine function deficiency after surgery(P<0.05).There was no significant difference in the incidence of diarrhea immediately after surgery,but at postoperative 12 mo,a significantly higher number of patients had diarrhea in the DP group than in the CP group(0%vs 9.5%;P<0.05).CONCLUSION CP is a generally safe procedure and is better than DP in preserving long-term pancreatic endocrine and exocrine functions.Therefore,CP might be a better option for treating benign or low-grade malignant neoplasms in suitable patients.展开更多
AIM:To evaluate the efficacy of autologous bone marrow mononuclear cell transplantation in decompensated liver disease.METHODS:Medline,EMBASE,PubMed,Science Direct,and the Cochrane Library were searched for relevant s...AIM:To evaluate the efficacy of autologous bone marrow mononuclear cell transplantation in decompensated liver disease.METHODS:Medline,EMBASE,PubMed,Science Direct,and the Cochrane Library were searched for relevant studies.Retrospective case-control studies were included along with randomized clinical trials.Metaanalysis was performed in line with recommendations from the Cochrane Collaboration software review manager.Heterogeneity was assessed using a randomeffects model.RESULTS:Four randomized controlled trials and four retrospective studies were included.Cell transplantation increased serum albumin level by 1.96 g/L(95%CI:0.74-3.17;P = 0.002],2.55 g/L(95%CI:0.32-4.79;P= 0.03),and 3.65 g/L(95%CI:0.76-6.54;P = 0.01)after 1,3,and 6 mo,respectively.Patients who had undergone cell transplantation also had a lower level of total bilirubin[mean difference(MD):-1.37 mg/dL;95%CI:-2.68-(-0.06);P = 0.04]after 6 mo.This decreased after 1 year when compared to standard treatment(MD:-1.26;95%CI:-2.48-(-0.03);P =0.04].A temporary decrease in alanine transaminase and aspartate transaminase were significant in the cell transplantation group.However,after 6 mo treatment,patients who had undergone cell transplantation had a slightly longer prothrombin time(MD:5.66 s,95%CI:0.04-11.28;P = 0.05).Changes in the model for endstage liver disease score and Child-Pugh score were not statistically significant.CONCLUSION:Autologous bone marrow transplantation showed some benefits in patients with decompensated liver disease.However,further studies are still needed to verify its role in clinical treatment for end-stage liver disease.展开更多
OBJECTIVES: To understand the characteristics of primary, liver camcer (PLC) in the elderly and summarize the experience in treatment of such patients. METHODS: The clinical data of PLC in the elderly group (≥60 year...OBJECTIVES: To understand the characteristics of primary, liver camcer (PLC) in the elderly and summarize the experience in treatment of such patients. METHODS: The clinical data of PLC in the elderly group (≥60 years, 125 patients) and the young group (≤59 years, 295 patients) were analyzed retrospectively. RESULTS: In the elderly group, 64 patients were found HBsAg positive, 39 patients small PLC, 24 large PLC, 15 tumor emboli in the portal vein, 86 AFP positive, and 34 hepatectomy performed. In the young group, 205 patients were found HBsAg positive, 79 patients small PLC, 97 large PLC, 96 tumor emboli in the portal vein, 200 AFP positive, and 126 hepatectomy performed. The median survival was 44 and 25 months respectively, and no significant difference was observed in the mortality between the two groups (P>0.05). CONCLUSIONS: Hepatectomy is a choice of treatment for PLC in the elderly based on their liver function. AFP and B-ultrasonography are important methods for the diagnosis of PLC in the elderly.展开更多
Objectives: To prevent and early diagnose hepatitis B virus reinfection and recurrent hepatitis B following liver transplantation, and to discuss the further treat- ment of recurrent hepatitis B. Methods: Liver transp...Objectives: To prevent and early diagnose hepatitis B virus reinfection and recurrent hepatitis B following liver transplantation, and to discuss the further treat- ment of recurrent hepatitis B. Methods: Liver transplantation recipients received lamivudine for prophylaxis of HBV reinfection. Viro- logical and biochemical data, serum HBV-DNA, and immunohistological staining for HBsAg and HBcAg in liver biopsy specimens were tested in due time. Results: Five patients with hepatitis B virus reinfection and two patients with hepatitis B recurrence were ob- served after liver transplantation. One patient with re- current hepatitis B developed chronic severe hepatitis B despite treatment. One patient improved after a se- ries of treatment. Conclusions: Hepatitis B virus reinfection or recurrent hepatitis B following liver transplantation occurs most- ly 6-12 months after operation. The diagnosis of hepa- titis B recurrence should be taken into account when liver biochemical data becomes poor during this pe- riod. The treatment for recurrent hepatitis B after liv- er transplantation includes increased dosage of lamivu- dine, application of famciclovir, and other liver pro- tection measures.展开更多
Although targeted therapies and immunotherapies have been effective againstseveral malignancies, the respective monotherapies are limited by low and/orshort-term responses. Specific inhibitors of oncogenic signaling p...Although targeted therapies and immunotherapies have been effective againstseveral malignancies, the respective monotherapies are limited by low and/orshort-term responses. Specific inhibitors of oncogenic signaling pathways andtumor-associated angiogenesis can activate the anti-tumor immune responses byincreasing tumor antigen presentation or intratumor T cell infiltration. Additionalinsights into the effects and mechanisms of targeted therapies on the induction ofanti-tumor immunity will facilitate development of rational and effective combinationstrategies that synergize rapid tumor regression and durable response. Inthis review, we have summarized the recent combinations of targeted therapiesand immunotherapies, along with the associated clinical challenges.展开更多
Surgery of the Liver and Biliary Tract, Editedby L. H. Blumgart and Y. Fong, Third Editionpp2180. with illus. London; Harcourt Pub-lishers Limited, UK. 2000. ISBN 0-7020-25011.Since the publication of the first and se...Surgery of the Liver and Biliary Tract, Editedby L. H. Blumgart and Y. Fong, Third Editionpp2180. with illus. London; Harcourt Pub-lishers Limited, UK. 2000. ISBN 0-7020-25011.Since the publication of the first and second edi-tions of 1988 and 1994, Surgery of the Liver andBiliary Tract has been considered by surgeons as asource of comprehensive and updated knowledgeon hepatobiliary and pancreatic surgery. Totally a new book, the third edition has un-dergone extensive changes in contents and struc-tures as compared with its predecessors. The bookis divided into two volumes consisting of morethan two thousand pages and one hundred and six-teen chapters, contributed by a total of one hun-展开更多
Objective: This study demonstrated that dexamethasone(DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α(TNF-α) during severe acute pancreatitis(SAP), a...Objective: This study demonstrated that dexamethasone(DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α(TNF-α) during severe acute pancreatitis(SAP), and improves the renal microcirculation. Methods: Ninety mice were evenly divided into 3 groups(Sham, SAP, and SAP+DEX). The SAP mice model was established by ligature of pancreatic duct and intraperitoneal injection of cerulein. Renal perfusion and function, and morphological changes of the glycocalyx were evaluated by laser Doppler velocimetry, electron microscopy, and histopathology(hematoxylin and eosin(H&E) staining), respectively. Serum levels of syndecan-1 and TNF-α were assessed by enzyme-linked immunosorbent assay(ELISA). The proàtectiveì effects of dexamethasone on the glycocalyx and renal microcirculation were evaluated. Results: Significantly high levels of serum TNF-α were detected 3 h after the onset of SAP. These levels might induce degradation of the glycocalyx and kidney hypoperfusion, resulting in kidney microcirculation dysfunction. The application of dexamethasone reduced the degradation of the glycocalyx and improved perfusion of kidney. Conclusions: Dexamethasone protects the endothelial glycocalyx from inflammatory degradation possibly initiated by TNF-α during SAP. This is might be a significant discovery that helps to prevent tissue edema and hypoperfusion in the future.展开更多
基金supported by the National Natural Science Foundation of China(31970696,81502975,81830089,U20A20378,82188102)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR22H160010)+2 种基金the National Key Research and Development Program(2019YFC1316000)the Zhejiang Provincial Key Research and Development Program(2019C03019)the Zhejiang Provincial College Student Science and Technology Innovation Activity Plan-College Student Innovation and Entrepreneurship Incubation Program(Young Talent Program)(2022R40122)。
文摘Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines.In spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.
文摘The initiation and progression of liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, are dependent on its tumor microenvironment. Immune cells are key players in the liver cancer microenvironment and show complicated crosstalk with cancer cells. Emerging evidence has shown that the functions of immune cells are closely related to cell metabolism. However, the effects of metabolic changes of immune cells on liver cancer progression are largely undefined. In this review, we summarize the recent findings of immunometabolism and relate these findings to liver cancer progression. We also explore the translation of the understanding of immunometabolism for clinical use.
基金Supported by the National Natural Science Foundation of China,No.81972207,No.81830089 and No.81502026Zhejiang Provincial Natural Science Foundation,No.LQ16H180002 and No.LY18H160026
文摘BACKGROUND Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide.Socioeconomic development,indicated by the Human Development Index(HDI),is closely interconnected with public health.But the manner in which social development and medical advances influenced liver cancer patients in the past decade is still unknown.AIM To investigate the influence of HDI on clinical outcomes for patients with existing liver cancer from 2008 to 2018.METHODS The HDI values were obtained from the United Nations Development Programme,the age-standardized incidence and mortality rates of liver cancer were obtained from the GLOBOCAN database to calculate the mortality-toincidence ratio,and the estimated 5-year net survival of patients with liver cancer was provided by the CONCORD-3 program.We then explored the association of mortality-to-incidence ratio and survival with HDI,with a focus on geographic variability across countries as well as temporal heterogeneity over the past decade.RESULTS From 2008 to 2018,the epidemiology of liver cancer had changed across countries.Liver cancer mortality-to-incidence ratios were negatively correlated and showed good fit with a modified“dose-to-inhibition response”pattern with HDI(r=-0.548,P<0.0001 for 2018;r=-0.617,P<0.0001 for 2008).Cancer survival was positively associated with HDI(r=0.408,P<0.01)and negatively associated with mortality-to-incidence ratio(r=-0.346,P<0.05),solidly confirming the interrelation among liver cancer outcome indicators and socioeconomic factors.Notably,in the past decade,the HDI values in most countries have increased alongside a decreasing tendency of liver cancer mortality-to-incidence ratios(P<0.0001),and survival outcomes have simultaneously improved(P<0.001),with significant disparities across countries.CONCLUSION Socioeconomic factors have a significant influence on cancer outcomes.HDI values have increased along with improved cancer outcomes,with significant disparities among countries.
基金supported by grants from the Project of Medical and Health Technology Platform of Zhejiang Province(2017RC003)the National High Technology Research and Development Pro-gram of China(SS2015AA020405)+4 种基金the General Program of the National Natural Science Foundation of China(81871925)the General Program of the National Natural Science Foundation of China(81672337)the Key Innovative Team for the Diagnosis and Treatment of Pancreatic Cancer of Zhejiang Province(2013TD06)the Key Program of National Natural Science Foundation of China(81530079)the Key Research and Development Project of Zhejiang Province(2015C03044)
文摘Background: The enhanced recovery after surgery (ERAS) protocol is an evidence-based perioperative care program aimed at reducing surgical stress response and accelerating recovery. However, a small propor- tion of patients fail to bene t from the ERAS program following pancreaticoduodenectomy. This study aimed to identify the risk factors associated with failure of ERAS program in pancreaticoduodenectomy. Methods: Between May 2014 and December 2017, 176 patients were managed with ERAS program fol-lowing pancreaticoduodenectomy. ERAS failure was indicated by prolonged hospital stay, unplanned read- mission or unplanned reoperation. Demographics, postoperative recovery and compliance were compared of those ERAS failure groups to the ERAS success group. Results: ERAS failure occurred in 59 patients, 33 of whom had prolonged hospital stay, 18 were readmitted to hospital within 30 days after discharge, and 8 accepted reoperation. Preoperative American Society of Anesthesiologists (ASA) score of ≥III (OR = 2.736;95% CI: 1.276 6.939;P=0.028) and albumin (ALB) level of <35g/L (OR=3.589;95% CI: 1.403 9.181;P=0.008) were independent risk factors associated with prolonged hospital stay. Elderly patients (>70 years) were on a high risk of unplanned reoperation (62.5% vs. 23.1%, P=0.026). Patients with prolonged hospital stay and unplanned reoperation had delayed intake and increased intolerance of oral foods. Prolonged stay patients got off bed later than ERAS success patients did (65h vs. 46h, P =0.012). Unplanned reoperation patients tended to experience severer pain than ERAS success patients did (3 score vs. 2 score, P =0.035). Conclusions: Patients with high ASA score, low ALB level or age >70 years were at high risk of ERAS failure in pancreaticoduodenectomy. These preoperative demographic and clinical characteristics are important determinants to obtain successful postoperative recovery in ERAS program.
基金Supported by The National Natural Science Funds for Distinguished Young ScholarsNo.30925033+1 种基金the Innovation and High-Level Talent Training Program of Department of Health of Zhejiang ProvinceChina
文摘AIM:To identify the role of human development in the incidence and mortality rates of gastrointestinal cancers worldwide.METHODS:The age-standardized incidence and mortality rates for gastrointestinal cancers,including cancers of the esophagus,stomach,pancreas,liver,gallbladder,and colorectum,were obtained from the GLOBOCAN 2008 database and United States Cancer Statistics(USCS)report.The human development index(HDI)data were calculated according to the 2011 Human Development Report.We estimated the mortality-toincidence ratios(MIRs)at the regional and national levels,and explored the association of the MIR with development levels as measured by the HDI using a modified"drug dose to inhibition response"model.Furthermore,countries were divided into four groups according to the HDI distribution,and the MIRs of the four HDI groups were compared by one-way ANOVA followed by the Tukey-Kramer post-hoc test.Statespecific MIRs in the United States were predicted from the estimated HDI using the fitted non-linear model,and were compared with the actual MIRs calculated from data in the USCS report.RESULTS:The worldwide incidence and mortality rates of gastrointestinal cancers were as high as 39.4and 54.9 cases per 100000 individuals,respectively.Linear and non-linear regression analyses revealed an inverse correlation between the MIR of gastrointestinal cancers and the HDI at the regional and national levels(<0;P=0.0028 for regional level and<0.0001 for national level,ANOVA).The MIR differed significantly among the four HDI areas(very high HDI,0.620±0.033;high HDI,0.807±0.018;medium HDI,0.857±0.021;low HDI,0.953±0.011;P<0.001,oneway ANOVA).Prediction of the MIRs for individual United States states using best-fitted non-linear models showed little deviation from the actual MIRs in the United States.Except for 28 data points(9.93%of282),the actual MIRs of all gastrointestinal cancers were mostly located in the prediction intervals via the best-fit non-linear regression models.CONCLUSION:The inverse correlation between HDI and MIR demonstrates that more developed areas have a relatively efficacious healthcare system,resulting in low MIRs,and HDI can be used to estimate the MIR.
文摘Objective: To sum up the experience in liver trans- plantation in a period of ten years at a single center. Methods: We retrospectively reviewed the clinical re- cords of 120 patients receiving liver transplantation from April 1993 to October 2002. The patients' cli- nical characteristics, surgical techniques, complica- tions and survival were compared in the phases of 1993-1997 (phase Ⅰ), 1999 (phase Ⅱ), and 2000- 2002 (phase Ⅲ). Results: Malignant liver diseases were major indica- tions for liver transplantation in phase Ⅰ(100%) and Ⅱ(53. 3%), but decreased markedly in percentage in phase Ⅲ(34. 0%). When compared with recipi- ents in phase Ⅰ and Ⅱ, the survival of recipients with benign liver diseases in phase Ⅲ was significantly im- proved with the 3-month, 6-month and 1-year sur- vival rates of 85. 7%, 84. 5% and 83. 1%, respec- tively. For patients with malignant liver diseases, the 3-month, 6-month and 1-year survival rates were 87. 4%, 81. 1% and 46. 0%, respectively. The rein- fection rate of hepatitis B virus was 24% 12 months after transplantation. With technical refinements, the incidence of postransplantation vascular compli- cations has significantly decreased from 29. 4% in phase Ⅰ and Ⅱ to 4. 9% in phase Ⅲ. Biliary compli- cations remained one of the major obstacles to long- term survival. No reno-venous bypass was applied in phase Ⅲ, providing a promising outcome. Conclusion: Strict selection of potential recipients, technical refinement, appropriate management of vascular and biliary complications, and prophylaxis of recurrences of hepatitis B and malignant liver dis- eases are important to obtain long-term survival of patients receiving liver transplantation in China.
文摘BACKGROUND Surgical site infections (SSI) remain a major cause of morbidity after hepatectomy for hepatocellular carcinoma (HCC).AIM To identify the risk factors associated with SSI,and develop a nomogram to predict SSI among patients undergoing hepatectomy.METHODS We retrospectively reviewed the data of patients diagnosed with HCC undergoing hepatectomy at two academic institutions in China,and evaluated the occurrence of SSI.Independent risk factors for SSI were identified using univariate and multivariate analyses.Based on these independent risk factors,a nomogram was established using the data of patients in the first institution,and was validated using data from an external independent cohort from the second institution.RESULTS The nomogram was established using data from 309 patients,whereas the validation cohort used data from 331 patients.The operation duration,serum albumin level,repeat hepatectomy,and ASA score were identified as independent risk factors.The concordance index (C-index) of the nomogram for SSI prediction in the training cohort was 0.86;this nomogram also performed well in the external validation cohort,with a C-index of 0.84.Accordingly,we stratified patients into three groups,with a distinct risk range based on the nomogram prediction,to guide clinical practice.CONCLUSION Our novel nomogram offers good preoperative prediction for SSIs in patients undergoing hepatectomy.
基金Supported by National Natural Science Funds for Distinguished Young Scholar,No.30925033National Natural Science Funds of China,No.30801101 and No.81171884Innovation and High-Level Talent Training Program of Department of Health of Zhejiang
文摘Sister Mary Joseph's nodule(SMJN) refers to a metastatic tumor of the umbilicus.It is a rare entity which arises from a malignancy in the intra-abdominal cavity.We herein describe a patient who presented with SMJN as his first sign of pancreatic cancer.It is an even more unusual case of SMJN.We therefore,suggest that pancreatic cancer should be included in the differential diagnosis when an umbilical mass is found.With the progress made in surgical procedures and other modalities,an early diagnosis will dramatically improve the prognosis of the patients.
文摘OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in PBMCs from 22 patients receiving liver transplantation, 13 patients with primary liver carcinoma (PLC), and 12 healthy controls. To determine whether 4-1BB molecule is also expressed on the surface of CD4^+ and CD8^+ T cell, flow cytometry was used to analyse the phenotype of T cell subsets from the blood of liver transplantation patients. RESULTS: 4-1BB mRNA was detected in PBMCs from stable survivors after liver transplantation, but almost not deteeted in PBMCs from PLC patients and healthy controls. Meanwhile, 4-1BB was almost not expressed on the surface of CD4^+ and CD8^+ T cells in healthy controls and PLC patients. A low level of 4-1BB expression, however, was found on the surface of CD4^+ and CD8^+ T cells from the stable survivors after liver transplantation. CONCLUSIONS: This study demonstrates that although patients are stable after liver transplantation, effector T-cells can also be activated through the signal of 4-1BB molecule and persistent irmmune response to grafts. Blockage of 4-1BB/4-1BBL pathway may benefitially reduce the clinical dosage of immunosuppressive agents and prolong the survival of grafts.
基金Supported by National Natural Science Foundation of China for Distinguished Young Scholars,No.30925033Innovation and High-Level Talent Training Program of Department of Health of Zhejiang Province,China
文摘Budd-Chiari syndrome(BCS)is defined as hepatic venous outflow obstruction at any level from the small hepatic veins to the junction of the inferior vena cava(IVC)and the right atrium,regardless of the cause of obstruction.We present two cases of acute iatrogenic BCS and our clinical management of these cases.The first case was a 43-year-old woman who developed acute BCS following the implantation of an IVC stent for the correction of stenosis in the IVC after hepatectomy for hepatolithiasis.The second case was a61-year-old woman with complete obstruction of the outflow of hepatic veins during bilateral hepatectomy for hepatolithiasis.Acute iatrogenic BCS should be con-sidered a rare complication following hepatectomy for hepatolithiasis.Awareness of potential hepatic outflow obstructions and timely management are critical to avoid poor outcomes when performing hepatectomy for hepatolithiasis.
文摘Objective: To sum up the preliminary experience in living related liver transplantation (LRLT). Methods: A 9-month-old male infant with biliary atresia (BA) who had undergone an unsuccessful Kasai operation was defined as a candidate for LR- LT. The donor was his 30-year-old mother. Her la- teral lobe of the left liver was transplanted into the infant's body as the graft. The left branches of the portal vein, left hepatic artery and left hepatic vein of the graft were end-to-end anastomosed to the por- tal vein, hepatic artery proper and hepatic vein of the recipient respectively. Biliary drainage was re- established via Roux-en-Y operation. Results: The donor retained her liver function within 2 weeks after the operation. Steroid and FK506 were prescribed in immunosuppressive therapy for the re- cipient. The blood bilirubin level of the infant de- creased to normal 2 weeks after operation. No acute rejection occurred. Biliary leakage in the early peri- od after the transplantation was controlled by drain- age, and E. coli infection was effectively treated with antibiotics. The donor and recipient are in satisfacto- ry condition to the present. Conclusion: LRLT is advisable for children with bili- ary atresia.
基金National Natural Science Foundation of China,No.81871320 and No.81830089Zhejiang Provincial Natural Science Foundation of China,No.LR20H160002.
文摘Hepatocellular carcinoma(HCC)is characterized by high heterogeneity in both intratumoral and interpatient manners.While interpatient heterogeneity is related to personalized therapy,intratumoral heterogeneity(ITH)largely influences the efficacy of therapies in individuals.ITH contributes to tumor growth,metastasis,recurrence,and drug resistance and consequently limits the prognosis of patients with HCC.There is an urgent need to understand the causes,characteristics,and consequences of tumor heterogeneity in HCC for the purposes of guiding clinical practice and improving survival.Here,we summarize the studies and technologies that describe ITH in HCC to gain insight into the origin and evolutionary process of heterogeneity.In parallel,evidence is collected to delineate the dynamic relationship between ITH and the tumor ecosystem.We suggest that conducting comprehensive studies of ITH using single-cell approaches in temporal and spatial dimensions,combined with population-based clinical trials,will help to clarify the clinical implications of ITH,develop novel intervention strategies,and improve patient prognosis.
文摘To the Editor:Liver transplantation remains the only cure for end-stage liver disease.Tacrolimus is widely used as a first-line immunosuppressive drug to prevent organ rejection after liver transplantation[1–3].However,tacrolimus has a narrow therapeutic index and wide inter-individual variability in pharmacokinetics,which can result in underimmunosuppression or toxicity.Orally administered tacrolimus is rapidly absorbed from the distal gastrointestinal tract and extensively metabolized in the liver and intestinal walls by cytochrome P450(CYP)3A4 and 3A5[2,4,5].
基金Supported by the National Natural Science Foundation of China,No.82172859,81801566,and 82071867the National Key Research and Development Program of China,No.2019YFC1316000.
文摘BACKGROUND For tumors in the neck and body of the pancreas,distal pancreatectomy(DP)has been the standard surgical procedure for the last few decades and central pancreatectomy(CP)is an alternative surgical option.Whether CP better preserves remnant pancreatic endocrine and exocrine functions after surgery remains a subject of debate.AIM To evaluate the safety and efficacy of CP compared with DP for benign or lowgrade malignant pancreatic tumors in the neck and body of the pancreas.METHODS This retrospective study enrolled 296 patients who underwent CP or DP for benign and low-malignant neoplasms at the same hospital between January 2016 and March 2020.Perioperative outcomes and long-term morbidity of endocrine/exocrine function were prospectively evaluated.RESULTS No significant difference was observed in overall morbidity or clinically relevant postoperative pancreatic fistula between the two groups(P=0.055).Delayed gastric emptying occurred more frequently in the CP group than in the DP group(29.4%vs 15.3%;P<0.005).None of the patients in the CP group had new-onset or aggravated distal metastasis,whereas 40 patients in the DP group had endocrine function deficiency after surgery(P<0.05).There was no significant difference in the incidence of diarrhea immediately after surgery,but at postoperative 12 mo,a significantly higher number of patients had diarrhea in the DP group than in the CP group(0%vs 9.5%;P<0.05).CONCLUSION CP is a generally safe procedure and is better than DP in preserving long-term pancreatic endocrine and exocrine functions.Therefore,CP might be a better option for treating benign or low-grade malignant neoplasms in suitable patients.
基金Supported by National Natural Science Foundation of China(No.81171884 and No.81401954)Innovation and HighLevel Talent Training Program of the Department of Health of Zhejiang Province,China
文摘AIM:To evaluate the efficacy of autologous bone marrow mononuclear cell transplantation in decompensated liver disease.METHODS:Medline,EMBASE,PubMed,Science Direct,and the Cochrane Library were searched for relevant studies.Retrospective case-control studies were included along with randomized clinical trials.Metaanalysis was performed in line with recommendations from the Cochrane Collaboration software review manager.Heterogeneity was assessed using a randomeffects model.RESULTS:Four randomized controlled trials and four retrospective studies were included.Cell transplantation increased serum albumin level by 1.96 g/L(95%CI:0.74-3.17;P = 0.002],2.55 g/L(95%CI:0.32-4.79;P= 0.03),and 3.65 g/L(95%CI:0.76-6.54;P = 0.01)after 1,3,and 6 mo,respectively.Patients who had undergone cell transplantation also had a lower level of total bilirubin[mean difference(MD):-1.37 mg/dL;95%CI:-2.68-(-0.06);P = 0.04]after 6 mo.This decreased after 1 year when compared to standard treatment(MD:-1.26;95%CI:-2.48-(-0.03);P =0.04].A temporary decrease in alanine transaminase and aspartate transaminase were significant in the cell transplantation group.However,after 6 mo treatment,patients who had undergone cell transplantation had a slightly longer prothrombin time(MD:5.66 s,95%CI:0.04-11.28;P = 0.05).Changes in the model for endstage liver disease score and Child-Pugh score were not statistically significant.CONCLUSION:Autologous bone marrow transplantation showed some benefits in patients with decompensated liver disease.However,further studies are still needed to verify its role in clinical treatment for end-stage liver disease.
文摘OBJECTIVES: To understand the characteristics of primary, liver camcer (PLC) in the elderly and summarize the experience in treatment of such patients. METHODS: The clinical data of PLC in the elderly group (≥60 years, 125 patients) and the young group (≤59 years, 295 patients) were analyzed retrospectively. RESULTS: In the elderly group, 64 patients were found HBsAg positive, 39 patients small PLC, 24 large PLC, 15 tumor emboli in the portal vein, 86 AFP positive, and 34 hepatectomy performed. In the young group, 205 patients were found HBsAg positive, 79 patients small PLC, 97 large PLC, 96 tumor emboli in the portal vein, 200 AFP positive, and 126 hepatectomy performed. The median survival was 44 and 25 months respectively, and no significant difference was observed in the mortality between the two groups (P>0.05). CONCLUSIONS: Hepatectomy is a choice of treatment for PLC in the elderly based on their liver function. AFP and B-ultrasonography are important methods for the diagnosis of PLC in the elderly.
文摘Objectives: To prevent and early diagnose hepatitis B virus reinfection and recurrent hepatitis B following liver transplantation, and to discuss the further treat- ment of recurrent hepatitis B. Methods: Liver transplantation recipients received lamivudine for prophylaxis of HBV reinfection. Viro- logical and biochemical data, serum HBV-DNA, and immunohistological staining for HBsAg and HBcAg in liver biopsy specimens were tested in due time. Results: Five patients with hepatitis B virus reinfection and two patients with hepatitis B recurrence were ob- served after liver transplantation. One patient with re- current hepatitis B developed chronic severe hepatitis B despite treatment. One patient improved after a se- ries of treatment. Conclusions: Hepatitis B virus reinfection or recurrent hepatitis B following liver transplantation occurs most- ly 6-12 months after operation. The diagnosis of hepa- titis B recurrence should be taken into account when liver biochemical data becomes poor during this pe- riod. The treatment for recurrent hepatitis B after liv- er transplantation includes increased dosage of lamivu- dine, application of famciclovir, and other liver pro- tection measures.
基金The National Key Research and Development Program of China,No.2019YFC1316000the National High Technology Research and Development Program of China,No.2015AA020405+1 种基金the National Natural Science Foundation of China,No.81672337China Postdoctoral Science Foundation,No.2020M671761.
文摘Although targeted therapies and immunotherapies have been effective againstseveral malignancies, the respective monotherapies are limited by low and/orshort-term responses. Specific inhibitors of oncogenic signaling pathways andtumor-associated angiogenesis can activate the anti-tumor immune responses byincreasing tumor antigen presentation or intratumor T cell infiltration. Additionalinsights into the effects and mechanisms of targeted therapies on the induction ofanti-tumor immunity will facilitate development of rational and effective combinationstrategies that synergize rapid tumor regression and durable response. Inthis review, we have summarized the recent combinations of targeted therapiesand immunotherapies, along with the associated clinical challenges.
文摘Surgery of the Liver and Biliary Tract, Editedby L. H. Blumgart and Y. Fong, Third Editionpp2180. with illus. London; Harcourt Pub-lishers Limited, UK. 2000. ISBN 0-7020-25011.Since the publication of the first and second edi-tions of 1988 and 1994, Surgery of the Liver andBiliary Tract has been considered by surgeons as asource of comprehensive and updated knowledgeon hepatobiliary and pancreatic surgery. Totally a new book, the third edition has un-dergone extensive changes in contents and struc-tures as compared with its predecessors. The bookis divided into two volumes consisting of morethan two thousand pages and one hundred and six-teen chapters, contributed by a total of one hun-
基金Project supported by the National Natural Science Foundation of China(No.81501644)
文摘Objective: This study demonstrated that dexamethasone(DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α(TNF-α) during severe acute pancreatitis(SAP), and improves the renal microcirculation. Methods: Ninety mice were evenly divided into 3 groups(Sham, SAP, and SAP+DEX). The SAP mice model was established by ligature of pancreatic duct and intraperitoneal injection of cerulein. Renal perfusion and function, and morphological changes of the glycocalyx were evaluated by laser Doppler velocimetry, electron microscopy, and histopathology(hematoxylin and eosin(H&E) staining), respectively. Serum levels of syndecan-1 and TNF-α were assessed by enzyme-linked immunosorbent assay(ELISA). The proàtectiveì effects of dexamethasone on the glycocalyx and renal microcirculation were evaluated. Results: Significantly high levels of serum TNF-α were detected 3 h after the onset of SAP. These levels might induce degradation of the glycocalyx and kidney hypoperfusion, resulting in kidney microcirculation dysfunction. The application of dexamethasone reduced the degradation of the glycocalyx and improved perfusion of kidney. Conclusions: Dexamethasone protects the endothelial glycocalyx from inflammatory degradation possibly initiated by TNF-α during SAP. This is might be a significant discovery that helps to prevent tissue edema and hypoperfusion in the future.
