Short-term decreased post transplant lymphoproliferative disorder risk after kidney transplantation using two novel regimens

BackgroundBelatacept is employed alongside calcineurin inhibitor (CNI) therapy to prevent graft rejection in kidney transplant patients who are Epstein-Barr virus (EBV) seropositive. Preliminary data suggested that rates of post-transplant lymphoproliferative disorder (PTLD) were higher in individuals treated with belatacept compared to CNI therapy alone.MethodsThe records of 354 adults who underwent kidney only transplantation from January 2015 through September 2021 at one medical center were evaluated. Patients underwent treatment with either low-doses of mycophenolate, tacrolimus and sirolimus (B⁰, n = 235) or low-doses of mycophenolate, tacrolimus and belatacept (B¹, n = 119). All recipients underwent induction with antithymocyte globulin and a rapid glucocorticosteroid taper. Relevant donor and recipient information were analyzed and endpoints of PTLD were assessed.ResultsThere were no cases of PTLD in either cohort within the study period. Recipients in the belatacept cohort experienced lower estimated glomerular filtration rates at 12 months (B⁰: 67.48 vs. B¹: 59.10, p = 0.0014). Graft failure at 12 (B⁰: 1.28% vs. B¹: 0.84%, p = 1.0) and 24 months (B⁰:2.55% vs. B¹: 0.84%, p = 0.431) were similar. There was no difference in rejection rates at 12 (B⁰: 1.27% vs. B¹: 2.52%, p = 0.408) or 24 months (B⁰: 2.12% vs. B¹: 2.52%, p = 1.000). Both groups had similar rates of malignancy, mortality and CMV/BK viremia.ConclusionNon-belatacept (MMF, tacrolimus and sirolimus) and belatacept-based (MMF, tacrolimus and belatacept) regimens do not appear to pose any increased risk of early onset PTLD. Both cohorts benefited from low rates of rejection, malignancy, mortality and graft failure. Recipients will continue to be monitored as PTLD can manifest as a long-term complication.     

siRNA沉默CD147基因对肝癌细胞的影响

目的 观察小分子干扰RNA(siRNA)沉默CD147基因在肝癌细胞HepG2中的表达,探讨CD147基因对肝癌细胞生长、凋亡的影响.方法 根据CD147 cDNA序列设计具有短发夹结构的两条DNA序列,与载体pSileneerTM4.1-CMV neo构建重组表达载体,鉴定后转染至HepG2细胞,Western blotting法检测抑制效果,MTT法检测细胞增殖情况,流式细胞术检测肿瘤细胞凋亡情况.结果 成功构建了针对CD147基因表达的干扰质粒,有效抑制了HepG2细胞增殖,促进了HepG2细胞凋亡.结论 CD147靶向RNA干扰重组表达栽体为肝癌的基因治疗提供了可能.     

黄芪首乌化纤汤与金水宝胶囊抗乙型肝炎肝纤维化疗效比较

目的：观察中药复方黄芪首乌化纤汤抗慢性乙型肝炎（慢性乙肝）肝纤维化的作用，寻找抗肝纤维化有效中药复方。方法：慢性乙肝肝纤维化患者９２例，随机分为黄芪首乌化纤汤治疗组４７例，虫草孢子菌丝制剂金水宝胶囊对照组４５例，进行为期４８周的对照治疗。对照治疗前后肝纤维化４项血清学指标：透明质酸（ＨＡ），层粘连蛋白（ＬＮ），Ⅲ型前胶原（ＰＣⅢ），Ⅳ型胶原（ＣⅣ）；肝功能主要指标，总胆红素（ＴＢ），丙氨酸转氨酶（     

Classification and regression tree analysis of acute‐on‐chronic hepatitis B liver failure: Seeing the forest for the trees

At present, there is no ideal model for predicting the short‐term outcome of patients with acute‐on‐chronic hepatitis B liver failure (ACHBLF). This study aimed to establish and validate a prognostic model by using the classification and regression tree (CART) analysis. A total of 1047 patients from two separate medical centres with suspected ACHBLF were screened in the study, which were recognized as derivation cohort and validation cohort, respectively. CART analysis was applied to predict the 3‐month mortality of patients with ACHBLF. The accuracy of the CART model was tested using the area under the receiver operating characteristic curve, which was compared with the model for end‐stage liver disease (MELD) score and a new logistic regression model. CART analysis identified four variables as prognostic factors of ACHBLF: total bilirubin, age, serum sodium and INR, and three distinct risk groups: low risk (4.2%), intermediate risk (30.2%‐53.2%) and high risk (81.4%‐96.9%). The new logistic regression model was constructed with four independent factors, including age, total bilirubin, serum sodium and prothrombin activity by multivariate logistic regression analysis. The performances of the CART model (0.896), similar to the logistic regression model (0.914, P=.382), exceeded that of MELD score (0.667, P<.001). The results were confirmed in the validation cohort. We have developed and validated a novel CART model superior to MELD for predicting three‐month mortality of patients with ACHBLF. Thus, the CART model could facilitate medical decision‐making and provide clinicians with a validated practical bedside tool for ACHBLF risk stratification.     

水飞蓟宾胶囊对非酒精性脂肪性肝病患者肝功能及血脂的影响

目的探讨水飞蓟宾胶囊在非酒精性脂肪性肝病治疗中的疗效。方法选择医院2011年5月至2012年5月收治的102例患者,随机分为2组。所有患者均给予减重及控制饮食等基础治疗,对照组51例患者口服维生素E胶丸100 mg,治疗组51例患者口服水飞蓟宾胶囊105 mg,均每日3次,疗程均为6个月。结果与治疗前比较,治疗后2组患者的肝功能包括丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)、谷氨酰转肽酶(GGT)水平均明显改善(P<0.05),血脂包括甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平均显著下降(P<0.05),高密度脂蛋白胆固醇(HDL-C)水平上升(P<0.05),且治疗组改善更显著(P<0.05)。治疗组总有效率高达90.20%,明显高于对照组(P<0.05)。治疗过程中两组均未出现明显不良反应。结论水飞蓟宾胶囊治疗非酒精性脂肪性肝病的疗效显著,可有效改善患者的肝功能及血脂水平,值得推广。     

A novel xenograft model of human hepatocellular carcinoma in immunocompetent mice based on the microcarrier-6

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors that threaten human health; thus, the establishment of an animal model with clinical features similar to human hepatocellular carcinoma is of important practical significance.MethodsTaking advantage of the novel microcarrier-6, human HCC cells were injected into immunocompetent mice to establish a novel human HCC patient-derived xenograft (PDX) model. Primary HCC cells were isolated from fresh hepatocellular carcinoma tissues, which were subsequently co-cultured with microcarrier-6 to construct a three-dimensional tumor cell culture model in vitro. The HCC-microcarrier complex was implanted into mice by subcutaneous inoculation, and the tumor formation time, tumor formation rate, and pathological manifestation were recorded. Changes of immune parameters in mice were detected by flow cytometry.ResultsThe success rate was 60% (6/10) in the establishment of hepatocellular carcinoma PDX mouse model, and the total tumor formation rate of the tumor-forming model is 90–100%. H&E staining and immunohistochemical experiments indicate that the model well retained the characteristics of the primary tumor. Interestingly, M2 macrophages in tumor-bearing mice increased significantly, and the levels of CD4⁺ T cells were significantly reduced.ConclusionsThrough the application of the microcarrier-6 in immunocompetent mice, we successfully established a novel human HCC PDX model, which can be used to better study and further elucidate the occurrence and pathogenic mechanism of HCC, improve the predictability of toxicity and drug sensitivity in HCC.     

Risk factors for acute rejection in liver transplantation and its impact on the outcomes of recipients

ObjectiveTo determine the risk factors for acute rejection in liver transplantation and its impact on the outcomes of the recipients.MethodsClinicopathological data of 290 patients who underwent liver transplantation from January 2012 to December 2021 at our center were retrospectively evaluated. Patients were grouped into an acute rejection (AR) group and a normal (NM) group based on the confirmed histopathological diagnosis of acute rejection. Univariate and multivariate logistic regression were used to determine the risk factors for acute rejection.Results244 patients were included in the study. Acute rejection occurred in 27 (11.1%) of the patients. Warm ischemia time (P = 0.137), cold ischemia time (P = 0.064) and chronic liver failure (P = 0.001) were potential risk factors for acute rejection. Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47–27.32) was the independent risk factor. There was no significant difference in overall survival between recipients with acute rejection and those without it (P = 0.985). The 1-, 3- and 5-year overall survival in the NM group was 98.1%, 85.7% and 78.6% respectively vs 88.9%, 82.5% and 82.5% respectively in the AR group.ConclusionAcute rejection does not appear to affect the long-term survival of the recipients. Only chronic liver failure was an independent risk factor for acute rejection. Our findings further illustrate that contradictions still exist on which factors influence acute rejection in liver transplant recipients.SummaryClinicopathological data of 290 liver transplant recipients at our center between January 2012 and December 2021 were retrospectively evaluated to determine the risk factors for acute rejection and its impact on the outcomes of the recipients. 244 patients were included in the analysis. 27 of the 244 experienced acute rejection. Propensity score matching was performed to reduce the confounding effect. Patients were assigned to an acute rejection group (n = 27) and a normal group (n = 54). Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47–27.32) was the determined to be independent risk factor for acute rejection. Acute rejection did not appear to affect the long-term survival of the recipients and there was no significant difference in overall survival between the patients with acute rejection and those without it.