BACKGROUND The impact of perioperative blood transfusion on short-and long-term outcomes in pediatric living donor liver transplantation(PLDLT)must still be ascertained,mainly among young children.Clinical and surgica...BACKGROUND The impact of perioperative blood transfusion on short-and long-term outcomes in pediatric living donor liver transplantation(PLDLT)must still be ascertained,mainly among young children.Clinical and surgical postoperative complications related to perioperative blood transfusion are well described up to three months after adult liver transplantation.AIM To determine whether transfusion is associated with early and late postoperative complications and mortality in small patients undergoing PLDLT.METHODS We evaluated the effects of perioperative transfusion on postoperative complications in recipients up to 20 kg of body weight,submitted to PLDLT.A total of 240 patients were retrospectively allocated into two groups according to postoperative complications:Minor complications(n=109)and major complications(n=131).Multiple logistic regression analysis identified the volume of perioperative packed red blood cells(RBC)transfusion as the only independent risk factor for major postoperative complications.The receiver operating characteristic curve was drawn to identify the optimal volume of the perioperative RBC transfusion related to the presence of major postoperative complications,defining a cutoff point of 27.5 mL/kg.Subsequently,patients were reallocated to a low-volume transfusion group(LTr;n=103,RBC≤27.5 mL/kg)and a high-volume transfusion group(HTr;n=137,RBC>27.5 mL/kg)so that the outcome could be analyzed.RESULTS High-volume transfusion was associated with an increased number of major complications and mortality during hospitalization up to a 10-year follow-up period.During a short-term period,the HTr showed an increase in major infectious,cardiovascular,respiratory,and bleeding complications,with a decrease in rejection complications compared to the LTr.Over a long-term period,the HTr showed an increase in major infectious,cardiovascular,respiratory,and minor neoplastic complications,with a decrease in rejection complications.Additionally,Cox hazard regression found that high-volume RBC transfusion increased the mortality risk by 3.031-fold compared to low-volume transfusion.The Kaplan-Meier survival curves of the studied groups were compared using log-rank tests and the analysis showed significantly decreased graft survival,but with no impact in patient survival related to major complications.On the other hand,there was a significant decrease in both graft and patient survival,with high-volume RBC transfusion.CONCLUSION Transfusion of RBC volume higher than 27.5 mL/kg during the perioperative period is associated with a significant increase in short-and long-term postoperative morbidity and mortality after PLDLT.展开更多
AIM: To identify risk factors associated with survival in patients retransplanted for hepatitis C virus(HCV) recurrence and to apply a survival score to this population.METHODS: We retrospectively identified 108 patie...AIM: To identify risk factors associated with survival in patients retransplanted for hepatitis C virus(HCV) recurrence and to apply a survival score to this population.METHODS: We retrospectively identified 108 patients retransplanted for HCV recurrence in eight European liver transplantation centers(seven in France, one in Spain). Data collection comprised clinical and laboratory variables, including virological and antiviral treatment data. We then analyzed the factors associated with survival in this population. A recently published score that predicts survival in retransplantation in patients with hepatitis C was applied. Because there are currently no uniform recommendations regarding selection of the best candidates for retransplantation in this setting, we also described the clinical characteristics of 164 patients not retransplanted, with F3, F4, or fibrosing cholestatic hepatitis(FCH) post-first graft presenting with hepatic decompensation. RESULTS: Overall retransplantation patient survival rates were 55%, 47%, and 43% at 3, 5, and 10 years, respectively. Patients who were retransplanted for advanced cirrhosis had survival rates of 59%, 52%, and 49% at 3, 5, and 10 years, while those retransplanted for FCH had survival rates of 34%, 29%, and 11%, respectively. Under multivariate analysis, and adjusting for the center effect and the occurrence of FCH, factors associated with better survival after retransplantation were: negative HCV viremia before retransplantation, antiviral therapy after retransplantation, non-genotype 1, a Model for End-stage Liver Disease(MELD) score < 25 when replaced on the waiting list, and a retransplantation donor age < 60 years. Although the numbers were small, in the context of the new antivirals era, we showed that outcomes in patientswho underwent retransplantation with undetectable HCV viremia did not depend on donor age and MELD score. The Andrés score was applied to 102 patients for whom all score variables were available, producing a mean score of 43.4(SD = 6.6). Survival rates after the date of the first decompensation post-first liver transplantation(LT1) in the liver retransplantation(re LT) group(94 patients decompensated) at 3, 5, and 10 years were 62%, 59%, and 51%, respectively, among 78 retransplanted individuals with advanced cirrhosis, and 42%, 32%, and 16% among 16 retransplanted individuals with FCH. In the non-re LT group with hepatic decompensation, survival rates were 27%, 18%, and 9% at 3, 5, and 10 years, respectively(P < 0.0001). Compared with non-retransplanted patients, retransplanted patients were younger at LT1(mean age 48 ± 8 years compared to 53 ± 9 years in the no re LT group, P < 0.0001), less likely to have human immunodeficiency virus(HIV) co-infection(4% vs 14% among no re LT patients, P = 0.005), more likely to have received corticosteroid bolus therapy after LT1(25% in re LT vs 12% in the no re LT group, P = 0.01), and more likely to have presented with sustained virological response(SVR) after the first transplantation(20% in the re LT group vs 7% in the no re LT group, P = 0.028).CONCLUSION: Antiviral therapy before and after retransplantation had a substantial impact on survival in the context of retransplantation for HCV recurrence, and with the new direct-acting antivirals now available, outcomes should be even better in the future.展开更多
AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by...AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution. RESULTS： In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 rain of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-kB was found between control and P-selectin antibody-treated livers. CONCLUSION： In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.展开更多
AIM:To clarify the mechanism by which bone marrow cells promote angiogenesis around transplanted islets.METHODS: Streptozotocin induced diabetic BALB/ c mice were transplanted syngeneically under the kidney capsule wi...AIM:To clarify the mechanism by which bone marrow cells promote angiogenesis around transplanted islets.METHODS: Streptozotocin induced diabetic BALB/ c mice were transplanted syngeneically under the kidney capsule with the following: (1) 200 islets (islet group: n=12), (2) 1-5×106 bone marrow cells (bone marrow group: n=11), (3) 200 islets and 1-5×106 bone marrow cells (islet + bone marrow group: n= 13), or (4) no cells (sham group:n=5). All mice were evaluated for blood glucose, serum insulin, serum nervegrowth factor (NGF) and glucose tolerance (GTT) up to postoperative day (POD) 14. Histological assessment for insulin, von Willebrand factor (vWF) and NGF was performed at POD 3, 7 and 14.RESULTS: Blood glucose level was lowest and serum insulin was highest in the islet + bone marrow group. Serum NGF increased in islet, bone marrow, and islet + bone marrow groups after transplantation, and there was a significant difference (P=0.0496, ANOVA) between the bone marrow and sham groups. The number of vessels within the graft area was signif icantly increased in both the bone marrow and islet + bone marrow groups at POD 14 as compared to the islet alone group (21.2 ± 3.6 in bone marrow, P=0.01, vs islet group, 22.6 ± 1.9 in islet + bone marrow, P = 0.0003, vs islet group, 5.3 ± 1.6 in islet-alone transplants). NGF was more strongly expressed in bone marrow cells compared with islets. CONCLUSION: Bone marrow cells produce NGF and promote angiogenesis. Islet co-transplantation with bone marrow is associated with improvement of islet graft function.展开更多
The coronavirus disease 2019(COVID-19)epidemic is a major public health emergency characterized by fast spread,a wide range of infections,and enormous control difficulty.Since the end of December 2019,Wuhan has become...The coronavirus disease 2019(COVID-19)epidemic is a major public health emergency characterized by fast spread,a wide range of infections,and enormous control difficulty.Since the end of December 2019,Wuhan has become the first core infection area of China's COVID-19 outbreak.Since March 2020,the domestic worst-hit areas have moved to the Heilongjiang Province due to the increased number of imported COVID-19 cases.Herein,we reported the major COVID-19 outbreak,which caused a rebound of the epidemic in Harbin,China.After the rebound,different levels of causes for the recurrence of COVID-19,including citylevel,hospital-level,and medical staff-level cause,were investigated.Meanwhile,corresponding countermeasures to prevent the recurrence of the epidemic were also carried out on the city level,hospital level,and medical staff level,which eventually showed the effect of infection control function in a pandemic.In this study,we described the complete transmission chain,analyzed the causes of the outbreak,and proposed corresponding countermeasures from our practical clinical experience,which can be used as a valuable reference for COVID-19 control.展开更多
This study was to determine whether GM-CSF induced WT1 gene expression and to establish an association with markers of proliferation CD71+CD34+ using nPCR and flow cytometry respectively, in samples obtained from 5 ne...This study was to determine whether GM-CSF induced WT1 gene expression and to establish an association with markers of proliferation CD71+CD34+ using nPCR and flow cytometry respectively, in samples obtained from 5 newly diagnosed JMML patients. Overtime (day 0 to day 14) there was an insignificant difference in WT1 gene expression and CD71+CD34+ in JMML samples when compared to peripheral blood of normal volunteers (n = 3). Our study suggests that there is a correlation between WT1 gene expression and cellular proliferation and that GMCSF in vitro does not create a significant difference in JMML samples.展开更多
The effector functions elicited by the fragment crystallizable (Fc) region of immunoglobulin G (IgG) antibodies are subject to variation by the presence of terminal sialic acid (Sia) residues at asparagine-297 (Asn-29...The effector functions elicited by the fragment crystallizable (Fc) region of immunoglobulin G (IgG) antibodies are subject to variation by the presence of terminal sialic acid (Sia) residues at asparagine-297 (Asn-297). We have previously shown that the sialic acid-containing (Sia<sup>+</sup>) fraction of intravenous immune globulin (IVIG) influences cell surface marker expression and cytokine/ chemokine secretion during the differentiation and maturation of human dendritic cells (DC). The present study examined the effects of Sia<sup>+</sup> IgG on human peripheral blood mononuclear cell (PBMC)-derived monocyte and macrophage surface marker expression and cytokine/chemokine secretion. Sia<sup>+</sup> IgG induced increased expression of CD80 and dendritic cell immunoreceptor (DCIR) on monocytes, whereas the expression of HLA-DR was decreased. In addition, the production of IL-6, TNFα, IL-1β, and CXCL1 by monocytes was profoundly increased by treatment with Sia<sup>+</sup> IgG. Sia<sup>+</sup> IgG also increased the expression of cell surface markers associated with macrophage polarization (e.g. CD40 and CD206) on monocytes. In macrophage-colony stimulating factor (MCSF) generated macrophages, Sia<sup>+</sup> IgG induced increased production of numerous cytokines/ chemokines including IL-6, TNFα, CXCL1, and IL-10, and the expression of the macrophage surface marker CD163. Our data extended prior observations of Sia<sup>+</sup> IgG on DC function and showed that Sia<sup>+</sup> IgG was able to differentially modulate multiple pathways in monocytes and macrophages. Our data indicate that the Sia<sup>+</sup> fraction of IVIG possesses the ability to influence inflammatory processes in multiple immune cell types and induces novel signatures in cell surface marker expression and cytokine/chemokine production.展开更多
Objective: The aim of this study was to evaluate intra- and inter-observer reproducibility of sinus x-rays in comparison to sinus computed tomography (CT) in chronic rhinosinusitis (CRS) patients. Methods: This was a ...Objective: The aim of this study was to evaluate intra- and inter-observer reproducibility of sinus x-rays in comparison to sinus computed tomography (CT) in chronic rhinosinusitis (CRS) patients. Methods: This was a prospective controlled study for which 14 adult CRS patients were recruited. Patients underwent a sinus multi-detector CT scan as well as additional sinus x-rays at the same time. Symptom interview and skin prick tests were performed. Lund-Mackay (LM) scores and 43 other findings in paranasal sinuses were analyzed by three blinded observers from CT-scans and x-rays. We compared agreement between sinus CT and x-rays (intra-observer reproducibility) and between three observers (inter-observer reproducibility) by Cohen’s kappa. Results: In at least 90% of the cases, the status of 47/49 structures was detectable in CT scans, whereas the status of only 8/49 structures was detectable in x-rays. The majority of the 25 visualized structures had poor intra-observer and inter-observer reproducibility. Conclusion: Only a few structures can be visualized in paranasal sinus x-rays and compared to paranasal sinus CT-scans, their reproducibility is poor. Our results strongly support the current consensus of radiation dose reduction by limiting the number of x-rays.展开更多
Background: After the failure of medical treatment, the surgery of chronic rhinosinusitis (CRS) is planned according to endoscopic and paranasal sinus computed tomography (CT) findings. Objective: The aim of this pros...Background: After the failure of medical treatment, the surgery of chronic rhinosinusitis (CRS) is planned according to endoscopic and paranasal sinus computed tomography (CT) findings. Objective: The aim of this prospective study was to evaluate whether this study method might be eligible in studies aiming at radiation dose reduction. Sinus CT scans were chosen as a model because of the high variation of the radiological anatomy of surgically important sinonasal structures. We hypothesized that 3 mm-slice-thick reconstruction CT had poor reproducibility. Methods: 59 CRS patients underwent routine multi-detector sinus CT (CT<sub>MD</sub>). CT<sub>3mm</sub> was reconstructed from CT<sub>MD</sub> data-sets. Lund-Mackay (LM) scores and 43 other structural parameters were analyzed blinded. Agreement was studied between CT<sub>MD</sub> and CT<sub>3mm</sub> (intra-observer reproducibility), and between three observers (inter-observer reproducibility) by using Cohen’s kappa. Results: The inter-observer agreement was moderate (kappa 0.4 - 0.6, p < 0.01) in the majority of structures of CT<sub>3mm</sub> scans. The intra-observer reproducibility of CT<sub>3mm</sub> scans was very good in most structures, however, it was poor in important structures such as frontal and spheno-ethmoid recess, lamina papyracae, and location of optic nerve or anterior ethmoidal artery. The grade of surgeon’s confidence of CT<sub>3mm</sub> in comparison to CT<sub>MD</sub> was lower (kappa 0.2 - 0.4, P < 0.05). Conclusion: This methodology might have some use in studies aiming at radiation dose reduction. As was expected, 3 mm-slice-thick reconstruction CT had poor reproducibility and surgeon’s confidence. More recent methods such as cone beam computed tomography scans have nowadays more relevant dose reduction potential.展开更多
Background:Clinical parameter-based nomograms and staging systems provide limited information for the prediction of survival in intrahepatic cholangiocarcinoma(ICC)patients.In this study,we developed a methylation sig...Background:Clinical parameter-based nomograms and staging systems provide limited information for the prediction of survival in intrahepatic cholangiocarcinoma(ICC)patients.In this study,we developed a methylation signature that precisely predicts overall survival(OS)after surgery.Methods:An epigenome-wide study of DNA methylation based on whole-genome bisulfite sequencing(WGBS)was conducted for two independent cohorts(discovery cohort,n=164;validation cohort,n=170)from three hepatobiliary centers in China.By referring to differentially methylated regions(DMRs),we proposed the concept of prognostically methylated regions(PMRs),which were composed of consecutive prognostically methylated CpGs(PMCs).Using machine learning strategies(Random Forest and the least absolute shrinkage and selector regression),a prognostic methylation score(PMS)was constructed based on 14 PMRs in the discovery cohort and confirmed in the validation cohort.Results:The C-indices of the PMS for predicting OS in the discovery and validation cohorts were 0.79 and 0.74,respectively.In the whole cohort,the PMS was an independent predictor of OS[hazard ratio(HR)=8.12;95% confidence interval(CI):5.48-12.04;P<0.001],and the C-index(0.78)of the PMS was significantly higher than that of the Johns Hopkins University School of Medicine(JHUSM)nomogram(0.69,P<0.001),the Eastern Hepatobiliary Surgery Hospital(EHBSH)nomogram(0.67,P<0.001),American Joint Committee on Cancer(AJCC)tumor-node-metastasis(TNM)staging system(0.61,P<0.001),and MEGNA prognostic score(0.60,P<0.001).The patients in quartile 4 of PMS could benefit from adjuvant therapy(AT)(HR=0.54;95%CI:0.32-0.91;log-rank P=0.043),whereas those in the quartiles 1-3 could not.However,other nomograms and staging system failed to do so.Further analyses of potential mechanisms showed that the PMS was associated with tumor biological behaviors,pathway activation,and immune microenvironment.Conclusions:The PMS could improve the prognostic accuracy and identify patients who would benefit from AT for ICC patients,and might facilitate decisions in treatment of ICC patients.展开更多
Recently,Lloyd Bod et al.published a study in Nature that identified the B-cell immune checkpoint T cell immunoglobulin and mucin domain 1(TIM-1)and mechanistically elucidated that targeting TIM-1 enhances the respons...Recently,Lloyd Bod et al.published a study in Nature that identified the B-cell immune checkpoint T cell immunoglobulin and mucin domain 1(TIM-1)and mechanistically elucidated that targeting TIM-1 enhances the responses to type I interferon(IFN-I),promotes B cells antigen presentation and activation,subsequently enhances anti-tumour responses of CD4^(+) and CD8^(+)T cells and inhibits tumour growth.This study provides important implications for anti-tumour therapy.展开更多
Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver cancer and causes major economic and health burdens throughout the world.Although the incidence of ICC is relatively low,an upward trend has ...Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver cancer and causes major economic and health burdens throughout the world.Although the incidence of ICC is relatively low,an upward trend has been seen over the past few decades.Owing to the lack of specific manifestations and tools for early diagnosis,most ICC patients have relatively advanced disease at diagnosis.Thus,neoadjuvant therapy is necessary to evaluate tumor biology and downstage these patients so that appropriate candidates can be selected for radical liver resection.However,even after radical resection,the recurrence rate is relatively high and is a main cause leading to death after surgery,which makes adjuvant therapy necessary.Because of its low incidence,studies in both neoadjuvant and adjuvant settings of ICC are lagging compared with other types of malignancy.While standard neoadjuvant and adjuvant regimens are not available in the current guidelines due to a lack of high-level evidence,some progress has been achieved in recent years.In this review,the available literature on advances in neoadjuvant and adjuvant strategies in ICC are evaluated,and possible challenges and opportunities for clinical and translational investigations in the near future are discussed.展开更多
Our understanding of immune responses to SARS-CoV-2 and variants of concern(VOCs)has been primarily acquired through analysis of Spike-specific IgG responses.However,a more comprehensive understanding of the breadth a...Our understanding of immune responses to SARS-CoV-2 and variants of concern(VOCs)has been primarily acquired through analysis of Spike-specific IgG responses.However,a more comprehensive understanding of the breadth and longevity of immune responses after infection and vaccination requires analysis of cellular immunity.Herein,we report on T cell immunity in infected and vaccinated individuals,identifying CD4+/CD8+T cell cytokine responses to SARS-CoV-2 and variant peptides(Alpha,B.1.1.7 and Delta,B.1.617.2).展开更多
To the Editor:The clinical spectrum of coronavirus disease 2019(COVID-19)appears to be wide,ranging from asymptomatic to severe progressive pneumonia with respiratory failure,multiorgan failure,and even death.Here,we ...To the Editor:The clinical spectrum of coronavirus disease 2019(COVID-19)appears to be wide,ranging from asymptomatic to severe progressive pneumonia with respiratory failure,multiorgan failure,and even death.Here,we investigated the clinical and pathological characteristics of a patient who died from severe COVID-19.Our findings will facilitate a deeper understanding of the pathogenesis and progression of COVID-19 and improve clinical strategies to combat the disease.On January 23,2020,a 57-year-old man without relevant history presented with fatigue and fever after attending a family party 2 days prior.Among the members of the family party,one relative had traveled from Wuhan.Over 9 days,the fever and cough developed,and the patient visited the emergency department.A throat swab was positive for severe acute respiratory syndrome coronavirus 2(SARS-COV-2)on real-time reverse-transcription polymerase chain reaction.He was admitted to the local hospital and received supportive therapies,anti-viral agents,atomized inhalation of interferon-γ,and oxygen therapy.Cough,fever,and dyspnea further developed on February 8.He received non-invasive mechanical ventilation therapy.On February 18,he was transferred to a superior hospital with shortness of breath.展开更多
文摘BACKGROUND The impact of perioperative blood transfusion on short-and long-term outcomes in pediatric living donor liver transplantation(PLDLT)must still be ascertained,mainly among young children.Clinical and surgical postoperative complications related to perioperative blood transfusion are well described up to three months after adult liver transplantation.AIM To determine whether transfusion is associated with early and late postoperative complications and mortality in small patients undergoing PLDLT.METHODS We evaluated the effects of perioperative transfusion on postoperative complications in recipients up to 20 kg of body weight,submitted to PLDLT.A total of 240 patients were retrospectively allocated into two groups according to postoperative complications:Minor complications(n=109)and major complications(n=131).Multiple logistic regression analysis identified the volume of perioperative packed red blood cells(RBC)transfusion as the only independent risk factor for major postoperative complications.The receiver operating characteristic curve was drawn to identify the optimal volume of the perioperative RBC transfusion related to the presence of major postoperative complications,defining a cutoff point of 27.5 mL/kg.Subsequently,patients were reallocated to a low-volume transfusion group(LTr;n=103,RBC≤27.5 mL/kg)and a high-volume transfusion group(HTr;n=137,RBC>27.5 mL/kg)so that the outcome could be analyzed.RESULTS High-volume transfusion was associated with an increased number of major complications and mortality during hospitalization up to a 10-year follow-up period.During a short-term period,the HTr showed an increase in major infectious,cardiovascular,respiratory,and bleeding complications,with a decrease in rejection complications compared to the LTr.Over a long-term period,the HTr showed an increase in major infectious,cardiovascular,respiratory,and minor neoplastic complications,with a decrease in rejection complications.Additionally,Cox hazard regression found that high-volume RBC transfusion increased the mortality risk by 3.031-fold compared to low-volume transfusion.The Kaplan-Meier survival curves of the studied groups were compared using log-rank tests and the analysis showed significantly decreased graft survival,but with no impact in patient survival related to major complications.On the other hand,there was a significant decrease in both graft and patient survival,with high-volume RBC transfusion.CONCLUSION Transfusion of RBC volume higher than 27.5 mL/kg during the perioperative period is associated with a significant increase in short-and long-term postoperative morbidity and mortality after PLDLT.
基金Supported by A research grant from Sao Paulo Research Foundation(FAPESP grant number 2012/03895-6)
文摘AIM: To identify risk factors associated with survival in patients retransplanted for hepatitis C virus(HCV) recurrence and to apply a survival score to this population.METHODS: We retrospectively identified 108 patients retransplanted for HCV recurrence in eight European liver transplantation centers(seven in France, one in Spain). Data collection comprised clinical and laboratory variables, including virological and antiviral treatment data. We then analyzed the factors associated with survival in this population. A recently published score that predicts survival in retransplantation in patients with hepatitis C was applied. Because there are currently no uniform recommendations regarding selection of the best candidates for retransplantation in this setting, we also described the clinical characteristics of 164 patients not retransplanted, with F3, F4, or fibrosing cholestatic hepatitis(FCH) post-first graft presenting with hepatic decompensation. RESULTS: Overall retransplantation patient survival rates were 55%, 47%, and 43% at 3, 5, and 10 years, respectively. Patients who were retransplanted for advanced cirrhosis had survival rates of 59%, 52%, and 49% at 3, 5, and 10 years, while those retransplanted for FCH had survival rates of 34%, 29%, and 11%, respectively. Under multivariate analysis, and adjusting for the center effect and the occurrence of FCH, factors associated with better survival after retransplantation were: negative HCV viremia before retransplantation, antiviral therapy after retransplantation, non-genotype 1, a Model for End-stage Liver Disease(MELD) score < 25 when replaced on the waiting list, and a retransplantation donor age < 60 years. Although the numbers were small, in the context of the new antivirals era, we showed that outcomes in patientswho underwent retransplantation with undetectable HCV viremia did not depend on donor age and MELD score. The Andrés score was applied to 102 patients for whom all score variables were available, producing a mean score of 43.4(SD = 6.6). Survival rates after the date of the first decompensation post-first liver transplantation(LT1) in the liver retransplantation(re LT) group(94 patients decompensated) at 3, 5, and 10 years were 62%, 59%, and 51%, respectively, among 78 retransplanted individuals with advanced cirrhosis, and 42%, 32%, and 16% among 16 retransplanted individuals with FCH. In the non-re LT group with hepatic decompensation, survival rates were 27%, 18%, and 9% at 3, 5, and 10 years, respectively(P < 0.0001). Compared with non-retransplanted patients, retransplanted patients were younger at LT1(mean age 48 ± 8 years compared to 53 ± 9 years in the no re LT group, P < 0.0001), less likely to have human immunodeficiency virus(HIV) co-infection(4% vs 14% among no re LT patients, P = 0.005), more likely to have received corticosteroid bolus therapy after LT1(25% in re LT vs 12% in the no re LT group, P = 0.01), and more likely to have presented with sustained virological response(SVR) after the first transplantation(20% in the re LT group vs 7% in the no re LT group, P = 0.028).CONCLUSION: Antiviral therapy before and after retransplantation had a substantial impact on survival in the context of retransplantation for HCV recurrence, and with the new direct-acting antivirals now available, outcomes should be even better in the future.
基金Supported by Grants from the American Liver Foundation, Naomi Judd Liver Scholar Award, The American Surgical Association Career Development Fellowship, and National Ⅰ
文摘AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution. RESULTS： In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 rain of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-kB was found between control and P-selectin antibody-treated livers. CONCLUSION： In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.
基金Supported by National Institutes of Health/National Instituteof Diabetes and Digestive and Kidney Diseases (NIH/NIDDK)Grant # 1R01-DK077541 (to Hathout E)a grant from the National Medical Test Bed (to Hathout E)
文摘AIM:To clarify the mechanism by which bone marrow cells promote angiogenesis around transplanted islets.METHODS: Streptozotocin induced diabetic BALB/ c mice were transplanted syngeneically under the kidney capsule with the following: (1) 200 islets (islet group: n=12), (2) 1-5×106 bone marrow cells (bone marrow group: n=11), (3) 200 islets and 1-5×106 bone marrow cells (islet + bone marrow group: n= 13), or (4) no cells (sham group:n=5). All mice were evaluated for blood glucose, serum insulin, serum nervegrowth factor (NGF) and glucose tolerance (GTT) up to postoperative day (POD) 14. Histological assessment for insulin, von Willebrand factor (vWF) and NGF was performed at POD 3, 7 and 14.RESULTS: Blood glucose level was lowest and serum insulin was highest in the islet + bone marrow group. Serum NGF increased in islet, bone marrow, and islet + bone marrow groups after transplantation, and there was a significant difference (P=0.0496, ANOVA) between the bone marrow and sham groups. The number of vessels within the graft area was signif icantly increased in both the bone marrow and islet + bone marrow groups at POD 14 as compared to the islet alone group (21.2 ± 3.6 in bone marrow, P=0.01, vs islet group, 22.6 ± 1.9 in islet + bone marrow, P = 0.0003, vs islet group, 5.3 ± 1.6 in islet-alone transplants). NGF was more strongly expressed in bone marrow cells compared with islets. CONCLUSION: Bone marrow cells produce NGF and promote angiogenesis. Islet co-transplantation with bone marrow is associated with improvement of islet graft function.
基金Supported by The National Natural Science Foundation of China,No.81770276,and No.81571871Nn10 Program of Harbin Medical University Cancer Hospital and Scientific Research Project of Heilongjiang Health and Family Planning Commission,No.2018086.
文摘The coronavirus disease 2019(COVID-19)epidemic is a major public health emergency characterized by fast spread,a wide range of infections,and enormous control difficulty.Since the end of December 2019,Wuhan has become the first core infection area of China's COVID-19 outbreak.Since March 2020,the domestic worst-hit areas have moved to the Heilongjiang Province due to the increased number of imported COVID-19 cases.Herein,we reported the major COVID-19 outbreak,which caused a rebound of the epidemic in Harbin,China.After the rebound,different levels of causes for the recurrence of COVID-19,including citylevel,hospital-level,and medical staff-level cause,were investigated.Meanwhile,corresponding countermeasures to prevent the recurrence of the epidemic were also carried out on the city level,hospital level,and medical staff level,which eventually showed the effect of infection control function in a pandemic.In this study,we described the complete transmission chain,analyzed the causes of the outbreak,and proposed corresponding countermeasures from our practical clinical experience,which can be used as a valuable reference for COVID-19 control.
文摘This study was to determine whether GM-CSF induced WT1 gene expression and to establish an association with markers of proliferation CD71+CD34+ using nPCR and flow cytometry respectively, in samples obtained from 5 newly diagnosed JMML patients. Overtime (day 0 to day 14) there was an insignificant difference in WT1 gene expression and CD71+CD34+ in JMML samples when compared to peripheral blood of normal volunteers (n = 3). Our study suggests that there is a correlation between WT1 gene expression and cellular proliferation and that GMCSF in vitro does not create a significant difference in JMML samples.
文摘The effector functions elicited by the fragment crystallizable (Fc) region of immunoglobulin G (IgG) antibodies are subject to variation by the presence of terminal sialic acid (Sia) residues at asparagine-297 (Asn-297). We have previously shown that the sialic acid-containing (Sia<sup>+</sup>) fraction of intravenous immune globulin (IVIG) influences cell surface marker expression and cytokine/ chemokine secretion during the differentiation and maturation of human dendritic cells (DC). The present study examined the effects of Sia<sup>+</sup> IgG on human peripheral blood mononuclear cell (PBMC)-derived monocyte and macrophage surface marker expression and cytokine/chemokine secretion. Sia<sup>+</sup> IgG induced increased expression of CD80 and dendritic cell immunoreceptor (DCIR) on monocytes, whereas the expression of HLA-DR was decreased. In addition, the production of IL-6, TNFα, IL-1β, and CXCL1 by monocytes was profoundly increased by treatment with Sia<sup>+</sup> IgG. Sia<sup>+</sup> IgG also increased the expression of cell surface markers associated with macrophage polarization (e.g. CD40 and CD206) on monocytes. In macrophage-colony stimulating factor (MCSF) generated macrophages, Sia<sup>+</sup> IgG induced increased production of numerous cytokines/ chemokines including IL-6, TNFα, CXCL1, and IL-10, and the expression of the macrophage surface marker CD163. Our data extended prior observations of Sia<sup>+</sup> IgG on DC function and showed that Sia<sup>+</sup> IgG was able to differentially modulate multiple pathways in monocytes and macrophages. Our data indicate that the Sia<sup>+</sup> fraction of IVIG possesses the ability to influence inflammatory processes in multiple immune cell types and induces novel signatures in cell surface marker expression and cytokine/chemokine production.
文摘Objective: The aim of this study was to evaluate intra- and inter-observer reproducibility of sinus x-rays in comparison to sinus computed tomography (CT) in chronic rhinosinusitis (CRS) patients. Methods: This was a prospective controlled study for which 14 adult CRS patients were recruited. Patients underwent a sinus multi-detector CT scan as well as additional sinus x-rays at the same time. Symptom interview and skin prick tests were performed. Lund-Mackay (LM) scores and 43 other findings in paranasal sinuses were analyzed by three blinded observers from CT-scans and x-rays. We compared agreement between sinus CT and x-rays (intra-observer reproducibility) and between three observers (inter-observer reproducibility) by Cohen’s kappa. Results: In at least 90% of the cases, the status of 47/49 structures was detectable in CT scans, whereas the status of only 8/49 structures was detectable in x-rays. The majority of the 25 visualized structures had poor intra-observer and inter-observer reproducibility. Conclusion: Only a few structures can be visualized in paranasal sinus x-rays and compared to paranasal sinus CT-scans, their reproducibility is poor. Our results strongly support the current consensus of radiation dose reduction by limiting the number of x-rays.
文摘Background: After the failure of medical treatment, the surgery of chronic rhinosinusitis (CRS) is planned according to endoscopic and paranasal sinus computed tomography (CT) findings. Objective: The aim of this prospective study was to evaluate whether this study method might be eligible in studies aiming at radiation dose reduction. Sinus CT scans were chosen as a model because of the high variation of the radiological anatomy of surgically important sinonasal structures. We hypothesized that 3 mm-slice-thick reconstruction CT had poor reproducibility. Methods: 59 CRS patients underwent routine multi-detector sinus CT (CT<sub>MD</sub>). CT<sub>3mm</sub> was reconstructed from CT<sub>MD</sub> data-sets. Lund-Mackay (LM) scores and 43 other structural parameters were analyzed blinded. Agreement was studied between CT<sub>MD</sub> and CT<sub>3mm</sub> (intra-observer reproducibility), and between three observers (inter-observer reproducibility) by using Cohen’s kappa. Results: The inter-observer agreement was moderate (kappa 0.4 - 0.6, p < 0.01) in the majority of structures of CT<sub>3mm</sub> scans. The intra-observer reproducibility of CT<sub>3mm</sub> scans was very good in most structures, however, it was poor in important structures such as frontal and spheno-ethmoid recess, lamina papyracae, and location of optic nerve or anterior ethmoidal artery. The grade of surgeon’s confidence of CT<sub>3mm</sub> in comparison to CT<sub>MD</sub> was lower (kappa 0.2 - 0.4, P < 0.05). Conclusion: This methodology might have some use in studies aiming at radiation dose reduction. As was expected, 3 mm-slice-thick reconstruction CT had poor reproducibility and surgeon’s confidence. More recent methods such as cone beam computed tomography scans have nowadays more relevant dose reduction potential.
基金supported by The National Key Technologies R&D Program of China(No.2018YFC1106800)The 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC18008)The Natural Science Foundation of China(Nos.91859105,81773012,81872004,81802302 and 81902401).
文摘Background:Clinical parameter-based nomograms and staging systems provide limited information for the prediction of survival in intrahepatic cholangiocarcinoma(ICC)patients.In this study,we developed a methylation signature that precisely predicts overall survival(OS)after surgery.Methods:An epigenome-wide study of DNA methylation based on whole-genome bisulfite sequencing(WGBS)was conducted for two independent cohorts(discovery cohort,n=164;validation cohort,n=170)from three hepatobiliary centers in China.By referring to differentially methylated regions(DMRs),we proposed the concept of prognostically methylated regions(PMRs),which were composed of consecutive prognostically methylated CpGs(PMCs).Using machine learning strategies(Random Forest and the least absolute shrinkage and selector regression),a prognostic methylation score(PMS)was constructed based on 14 PMRs in the discovery cohort and confirmed in the validation cohort.Results:The C-indices of the PMS for predicting OS in the discovery and validation cohorts were 0.79 and 0.74,respectively.In the whole cohort,the PMS was an independent predictor of OS[hazard ratio(HR)=8.12;95% confidence interval(CI):5.48-12.04;P<0.001],and the C-index(0.78)of the PMS was significantly higher than that of the Johns Hopkins University School of Medicine(JHUSM)nomogram(0.69,P<0.001),the Eastern Hepatobiliary Surgery Hospital(EHBSH)nomogram(0.67,P<0.001),American Joint Committee on Cancer(AJCC)tumor-node-metastasis(TNM)staging system(0.61,P<0.001),and MEGNA prognostic score(0.60,P<0.001).The patients in quartile 4 of PMS could benefit from adjuvant therapy(AT)(HR=0.54;95%CI:0.32-0.91;log-rank P=0.043),whereas those in the quartiles 1-3 could not.However,other nomograms and staging system failed to do so.Further analyses of potential mechanisms showed that the PMS was associated with tumor biological behaviors,pathway activation,and immune microenvironment.Conclusions:The PMS could improve the prognostic accuracy and identify patients who would benefit from AT for ICC patients,and might facilitate decisions in treatment of ICC patients.
基金the Key Research and Development Project of Sichuan Provincial Science and Technology Department(No.23ZDYF2875).
文摘Recently,Lloyd Bod et al.published a study in Nature that identified the B-cell immune checkpoint T cell immunoglobulin and mucin domain 1(TIM-1)and mechanistically elucidated that targeting TIM-1 enhances the responses to type I interferon(IFN-I),promotes B cells antigen presentation and activation,subsequently enhances anti-tumour responses of CD4^(+) and CD8^(+)T cells and inhibits tumour growth.This study provides important implications for anti-tumour therapy.
基金supported by grants from the National Key Technologies R&D Program(2018YFC1106800)the Natural Science Foundation of China(82002572,82002967,81972747 and 81872004)+1 种基金the fellowship of China National Postdoctoral Program for Innative Talents(BX20200225,BX20200227)the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYJC18008).
文摘Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver cancer and causes major economic and health burdens throughout the world.Although the incidence of ICC is relatively low,an upward trend has been seen over the past few decades.Owing to the lack of specific manifestations and tools for early diagnosis,most ICC patients have relatively advanced disease at diagnosis.Thus,neoadjuvant therapy is necessary to evaluate tumor biology and downstage these patients so that appropriate candidates can be selected for radical liver resection.However,even after radical resection,the recurrence rate is relatively high and is a main cause leading to death after surgery,which makes adjuvant therapy necessary.Because of its low incidence,studies in both neoadjuvant and adjuvant settings of ICC are lagging compared with other types of malignancy.While standard neoadjuvant and adjuvant regimens are not available in the current guidelines due to a lack of high-level evidence,some progress has been achieved in recent years.In this review,the available literature on advances in neoadjuvant and adjuvant strategies in ICC are evaluated,and possible challenges and opportunities for clinical and translational investigations in the near future are discussed.
文摘Our understanding of immune responses to SARS-CoV-2 and variants of concern(VOCs)has been primarily acquired through analysis of Spike-specific IgG responses.However,a more comprehensive understanding of the breadth and longevity of immune responses after infection and vaccination requires analysis of cellular immunity.Herein,we report on T cell immunity in infected and vaccinated individuals,identifying CD4+/CD8+T cell cytokine responses to SARS-CoV-2 and variant peptides(Alpha,B.1.1.7 and Delta,B.1.617.2).
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.81770276,81772045,and 81902000)Novel coronavirus pneumonia emergency treatment and diagnosis technology research project of Heilongjiang Provincial Science and Technology Department,Nn10 program of Harbin Medical University Cancer Hospital and Scientific research project of Heilongjiang health and Family Planning Commission(No.2018086)。
文摘To the Editor:The clinical spectrum of coronavirus disease 2019(COVID-19)appears to be wide,ranging from asymptomatic to severe progressive pneumonia with respiratory failure,multiorgan failure,and even death.Here,we investigated the clinical and pathological characteristics of a patient who died from severe COVID-19.Our findings will facilitate a deeper understanding of the pathogenesis and progression of COVID-19 and improve clinical strategies to combat the disease.On January 23,2020,a 57-year-old man without relevant history presented with fatigue and fever after attending a family party 2 days prior.Among the members of the family party,one relative had traveled from Wuhan.Over 9 days,the fever and cough developed,and the patient visited the emergency department.A throat swab was positive for severe acute respiratory syndrome coronavirus 2(SARS-COV-2)on real-time reverse-transcription polymerase chain reaction.He was admitted to the local hospital and received supportive therapies,anti-viral agents,atomized inhalation of interferon-γ,and oxygen therapy.Cough,fever,and dyspnea further developed on February 8.He received non-invasive mechanical ventilation therapy.On February 18,he was transferred to a superior hospital with shortness of breath.
