小鼠骨髓基质干细胞体外转化为肝细胞最佳诱导体系的筛选及验证

目的:采用均匀设计法筛选及验证小鼠骨髓基质干细胞体外转化为肝细胞的最佳诱导培养体系.方法:获取小鼠骨髓基质干细胞,根据均匀设计法分8组进行体外诱导实验.通过流式细胞术检测各组ALB及CK18的阳性表达率,通过逐步回归分析法确立最佳细胞因子组合及浓度.从基因水平、蛋白水平以及细胞合成代谢功能检测.证实诱导的细胞为有功能的肝细胞.结果:FGF取35 μg/L,OSM取30μg/L时,ALB及CK18的阳性细胞达到最高值.采用该最佳诱导体系诱导过程中可检测到细胞表达ALBmRNA、CK18 mRNA、AFP mRNA、TTRmRNA:以及ALB、CK18蛋白表达:第21天最佳体系诱导组ALB阳性细胞的比例为82.83%±9.03%.CK18阳性细胞的比例为74.79%±8.41%.诱导培养过程中细胞分泌尿素及白蛋白,且随诱导时间的延长而增强.结论:均匀设计法可有效进行最佳诱导体系的筛选,以35 μg/LFGF、30μg/LOSM为主的诱导培养体系,可以有效地促进骨髓基质干细胞体外定向转化为有功能的肝细胞.     

生物人工肝研究现状及进展

肝功能衰竭病情凶险,进展迅速,预后较差,各种药物治疗效果不佳,肝移植是治疗肝衰竭病人惟一有效的手段.但是,由于供体器官缺乏、费用高昂、需长期使用免疫抑制剂等原因,病人往往在等待供体过程中由于病情进展而迅速死亡,生物人工肝(bioartificial liver,BAL)可为病人提供短暂的肝功能支持,从而成为人们研究的焦点.本文从细胞来源、细胞培养方式及生物反应器三方面综述BAL目前的研究现状及近年来的进展.     

中晚期胆囊癌的外科治疗策略:附17例报告

目的 探讨中晚期胆囊癌(NevinⅢ～Ⅴ期)的外科治疗方法,进一步提高患者存活时间.方法 结合文献,联系17例中晚期胆囊癌的围手术期临床资料及随访数据,着重从患者术前诊断、手术治疗策略、术后并发症及存活时间等方面进行探讨.结果 通过术前多种影像学资料相互印证,可以诊断中晚期胆囊癌并对分期做出判断,但是不能避免误诊;手术治疗中晚期胆囊癌的要点在于手术范围的确定,特别是淋巴结彻底清扫的程度,本组13a淋巴结阳性率35.3%;8淋巴结阳性率23.5%,说明为了尽量保证肿瘤无残留必要时可适当扩大手术范围;手术后并发症主要包括腹腔感染、胆瘘和麻痹性肠梗阻.结论 中晚期胆囊癌外科治疗需要适当手术范围,术中肿瘤无残留可以使患者存活较长时间.

Abstract：

Objective To explore the optimal surgical treatment strategy of advanced gallbladder carcinoma (Nevin Ⅲ - Ⅴ ), with an aim to prolong patients' overall survival. Methods 17 patients with advanced gallbladder carcinoma were reviewed. Their preoperative diagnosis, surgical treatment, complications and survival time were studied. Results The diagnosis of advanced gallbladder carcinoma was done using different medical imaging techniques, but incorrect diagnosis still happened. There is a wide range of surgical treatment for advanced gallbladder carcinoma. Controversy still exists as whether lymph node resection should be done. In our patients, 35.3% of the 13a lymph nodes and 23. 5% of the 8 lymph nodes were positive for metastasis, which showed that lymph node resection should be carried out. Extended surgery was sometime required to ensure a R0 resection.The main complications of surgery were intraabdominal infection, bile leakage and paralytic ileus.Conclusion An aggressive surgical approach for advanced gallbladder carcinoma is required to ensure a R0 resection, which contributed to better overall survival.     

肝再生发生及其相关机制的研究进展

肝脏再生是指因手术、创伤、中毒、感染、坏死等致部分肝细胞功能丧失后,肝细胞重新修复的过程.对于肝再生的发生及其内在机制的认识和研究,大致可分为三个阶段:(1)最初认为可能存在一种特定的激素类物质决定肝再生的过程.     

体外生物人工肝支持系统治疗肝功能衰竭的系统评价

背景：生物人工肝支持系统由生物反应器和细胞材料组成,治疗过程中可部分替代肝脏的主要功能如解毒、合成、分泌和生物转化等功能。目的：回顾和评价体外生物人工肝支持系统近15年来治疗肝功能衰竭的疗效。方法：检索1995至2009年PubMed和Cochrane数据库有关生物人工肝支持系统的临床研究。被纳入的研究类型包括随机对照试验、临床对照试验和病例报告。结果与结论：共纳入31项研究,在生物人工肝支持系统治疗之后,患者生化指标呈现好转趋势,且大部分患者神经系统症状均得到改善,但多数患者生存率未见明显改善。说明尽管生物人工肝支持系统被证明具有一定治疗效果,但今后仍然有许多方面需要改进。     

兔慢性肝损害急性肝衰竭动物模型的建立

目的 建立新西兰兔的慢加急性肝衰竭(ACLF)动物模型.方法 将75只新西兰兔随机分为实验组(n=70)与对照组(n=5),实验组采用四氯化碳(CCl4)腹腔注射建立兔代偿性肝纤维化模型,每周2次,通过体质量及谷丙转氨酶(ALT)/谷草转氨酶(AST)改变调整药物剂量,共10周,获得48只肝纤维化新西兰兔,在此基础上将动物随机分为4组(n=12),Ⅰ组:继续腹腔注射CCl4,Ⅱ组:静脉注射D-氨基半乳糖(D-Gal)0.65 g/kg,Ⅲ组:静脉注射D-Gal 0.70 g/kg,Ⅳ组:静脉注射D-氨基半乳糖0.75 g/kg,观察各组动物的一般情况、生化指标及病理改变.结果 与对照组比较,肝纤维化实验组兔10周时ALT、AST、ALB、γ-谷氨酰转肽酶(GGT)、透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)差异均有统计学意义(P＜0.05),可观察到肝纤维化的病理表现,出现典型的假小叶,在肝纤维化基础给予D-Gal后,Ⅰ组动物全部存活,生化指标轻度改变;Ⅱ组动物死亡率为33.3%(4/12),生化指标仅出现一过性的改变;Ⅲ组动物死亡率为83.3%(10/12),平均存活时间为(53.00±25.69)h,给药后12 h生化指标及临床表现出现改变,48 h达到高峰,病理显示肝脏大块坏死;Ⅳ组动物均死于肝衰竭,平均存活时间为(32.70±17.46)h,肝损害出现时间早,损伤剧烈.结论 对CCl4诱导的肝纤维化新西兰兔给予D-Gal急性攻击可建立ACLF模型.其中给予D-Gal 0.70 g/kg的模型稳定性好,能较大程度上的模拟临床上ACLF的病理生理过程.

Abstract：

Objective To establish an ideal animal model of acute-on-chronic liver failure (ACLF) in New Zealand white rabbits in order to provide a large animal model for further researches.Methods Totally 75 New Zealand rabbits were randomly divided into experimental group (n =70) and control group (n = 5 ). Rabbits in the experimental group were injected with CCl4 into the abdominal cavity twice every week and the doses of CCl4 were modified according to the index of liver function and the body weight, whereas those in the control group were treated with the same volume of saline. At the 10th week,48 New Zealand rabbits with hepatic fibrosis were randomly assigned to 4 groups and injected with CCl4 as before, D-Gal at a dose of 0. 65 g/kg body weight (BW), 0. 70 g/kg BW and 0. 75 g/kg BW, respectively. By observing and comparing the general state, survival time, biochemical indexes, and the histopathology, a method of establishing a stable animal model of acute hepatic failure was found. Results As compared with those in control group, the levels of ALT, AST, GGT, HA, LN and PC-Ⅲ in the experiment group were increased significantly, while the level of ALB was decreased at the end of 10 weeks. Typical features of hepatic fibrosis and the formation of pseudo-lobules were observed at the end of 10 weeks. After treatment with D-Gal, all rabbits in group Ⅰ survived with minimal changes in liver function tests. In group Ⅱ , there was a temporary hepatic injury, but no hepatic coma. Four of the 12 rabbits died (33. 3% ). In group Ⅲ , biochemical indexes changed obviously 12 h after the administration and hepatic injury reached its peak after 48 h. Ten of 12 rabbits were died of severe hepatic failure with a survival time of ( 53. 00 ± 25. 69) h. Histology of liver section revealed massive necrosis in nodules. In group Ⅳ , hepatic injury occurred early and severely. All the rabbits died of severe hepatic failure with a survival time of (32. 70 ± 17. 46) h. Conclusion The experimental model of ACLF could be established by injected with D-Gal in New Zealand rabbits with hepatic fibrosis, induced by CCl4 intraperitoneal injection for 10 weeks.The one induced by 0. 70 g/kg of D-galactosamine was more stable and showed similar clinical pathophysiological changes in human beings. So it can be a good experimental platform for studies of ACLF.     

UW器官保存液感染对肝移植术后恢复的影响

[摘 要] 目的 了解UW器官保存液（简称UW液）感染对肝移植术后恢复的影响。方法 收集2014年6月至2017年4月期间南京鼓楼医院行同种异体原位肝移植术的患者临床资料,共68例,将供肝保存液UW液感染后的病例划为阳性组,未被感染的划为阴性组,对比分析两组患者术后肝功能、急性肾损伤（AKI）的发生及术后感染情况。结果 两组患者肝移植术后第1、3、7、10天肝功能的恢复未见明显差异（P＞0.05）。阳性组患者术后AKI的发生率为45.7%,阴性组18.1%,阳性组明显高于阴性组（P=0.028）。阳性组中UW液培养见两种细菌和（或）真菌的患者术后血培养及腹水培养较阴性组有明显升高（P值分别为0.01、0.039）。结论 UW液感染后可增加术后AKI的发生,其中UW液培养见两种细菌和（或）真菌会增加术后血液感染及腹腔积液感染发生率。     

MSCs移植治疗肝切除术后肝衰竭的应用及进展

肝大部切除术后肝衰竭的病死率极高,是非常危重的肝脏手术并发症,并且尚无有效治疗手 段,目前仍然以控制症状为主。间充质干细胞（mesenchymal stem cells,MSCs）因免疫调节、减轻炎症反应 能力被广泛研究。此外,MSCs具有促增殖和抗凋亡的特性,可以促进肝脏的修复和再生。综上,MSCs移 植成为治疗肝大部切除术后肝衰竭的研究热点,本文对MSCs的治疗效果及其促进肝脏修复的机制作一综 述。     

术前临床指标对肝细胞癌患者微血管侵犯分级的预测价值

目的 通过对根治性肝切除患者术前临床指标综合分析构建术前预测模型,预测肝细胞癌（HCC）患者是否合并微血管侵犯（MVI）,并验证其预测效能。方法 对2017年3月至2022年6月在南京鼓楼医院肝胆外科收治的579例肝切除HCC患者的临床资料进行回顾性研究,根据手术时间顺序分为模型组279例和验证组300例。采用单因素与多因素Logistic回归分析术前临床指标影响MVI分级的独立危险因素,并建立预测评分模型,通过ROC曲线判断MVI的诊断价值,并在验证组中进行独立验证。结果多因素Logistic回归分析显示,肿瘤最大径>5 cm(OR=8.356,95%CI 3.950～17.675,P<0.001)、肿瘤数目为多个（OR=8.652,95%CI 3.213～23.302,P<0.001）、肿瘤包膜强化（OR=4.636,95%CI 2.266～9.483,P<0.001）及AFP>400μg/L(OR=8.938,95%CI 4.182～19.105,P<0.001)为MVI分级的独立危险因素。根据Logistic回归分析结果构建预测模型,ROC曲...     

胆管乳头状腺瘤一例报告及文献复习

<正>胆管乳头状腺瘤为胆管良性肿瘤,WHO将腺瘤分为乳头状腺瘤、管状腺瘤和乳头管状腺瘤,临床以乳头状腺瘤居多[1]。但临床仍较少见,很容易被误诊。胆管乳头状腺瘤目前相关发病机制仍不是很明确,且缺乏统一命名,无法进行系统性研究。结合相关文献报道,该病可能与胆道结石、胆道炎症、胰胆管合流异常、先天性胆总管囊肿等有关[2-3]。本文回顾性分析南京鼓楼医院2016年2月收治的一例胆管乳头状腺瘤患者资料,就其临床表现、影像学表现及治疗方法进行总结。