Autophagy regulates biliary differentiation of hepatic progenitor cells through Notch1 signaling pathway

Autophagy plays important roles in self-renewal and differentiation of stem cells. Hepatic progenitor cells (HPCs) are thought to have the ability of self-renewal as well as possess a bipotential capacity, which allows them to differentiate into both hepatocytes and bile ductular cells. However, how autophagy contributes to self-renewal and differentiation of hepatic progenitor cells is not well understood. In this study, we use a well-established rat hepatic progenitor cell lines called WB-F344, which is treated with 3.75 mM sodium butyrate (SB) to promote the differentiation of WB-F344 along the biliary phenotype. We found that autophagy was decreased in the early stage of biliary differentiation, and maintained a low level at the late stage. Activation of autophagy by rapamycin or starvation suppressed the biliary differentiation of WB-F344. Further study reported that autophagy inhibited Notch1 signaling pathway, which contributed to biliary differentiation and morphogenesis. In conclusions, autophagy regulates biliary differentiation of hepatic progenitor cells through Notch1 signaling pathway.     

胆囊结石患者结石形态学特征及血浆脂多糖水平与急性胆源性胰腺炎的关系研究

摘要 目的：探讨胆囊结石患者结石形态学特征及血浆脂多糖（LPS）水平与急性胆源性胰腺炎（ABP）的关系。方法：选取2015年10月~2018年9月期间武汉大学人民医院收治的胆囊结石患者164例为研究对象,分析结石形态学特征与并发ABP的关系,同时采用Logistic回归分析ABP发生的危险因素。将所有患者根据LPS水平分为低LPS组（n=65,<10 pg/mL）以及高LPS组（n=99,≥10 pg/mL）,分析血浆LPS水平对不同结石大小、不同总胆固醇（TG）水平患者并发ABP的影响。结果：多发胆囊结石、球状结石、<3 mm结石、软碎型结石患者并发ABP的概率明显高于单发胆囊结石、不规则状结石或泥沙状结石、3~10 mm结石或>10 mm结石、硬型结石或胶冻型结石（P<0.05）。Logistic回归分析结果显示,多发胆囊结石、球状结石、<3 mm结石以及软碎型结石均是ABP发生的高危因素（P<0.05）。当患者处于高TG水平时,高LPS组并发ABP的概率高于低LPS组（P<0.05）,在细小结石患者中,高LPS组并发ABP的概率高于低LPS组（P<0.05）。结论：依据结石形态学特征可对胆囊结石患者并发ABP的可能性作出早期的判断,同时血浆LPS水平升高是高TG以及细小胆囊结石患者易并发ABP的重要因素之一。     

中国结节性硬化症患者的临床特点及诊断现状分析

目的:回顾结节性硬化症(TSC)在中国的诊断现状,分析中国TSC患者的临床特点,促进TSC的识别、规范化诊治和管理。方法:在维普数据库、万方数据库、中国知网、中国生物医学文献数据库、PubMed数据库中全面检索2001年-2014年13年间国内外发表的关于中国患者TSC的269篇所涉及的3171例TSC患者从皮肤、神经系统、肾脏、心脏、肺等多系统的临床特点对文献进行了统计和分析,并对TSC患者遗传学方面的基因检测情况进行了归纳和总结。结果:对照2012年TSC诊断指南,在对诊断标准中主要指征的报道中,共有247篇文献对2607例TSC患者的皮肤损害进行了描述,212篇文献对2395例TSC患者的神经系统损害的影像学表现进行了报道,有55篇文献报道了对348例患者进行的眼底检查中发现多发性视网膜错构瘤84例,32篇文献报道了对282例患者进行的心脏彩超检查中发现162例心脏横纹肌瘤,45篇文献在对282例患者进行的胸片检查、20篇文献在对36例患者进行的胸部CT检查中共发现淋巴管肌瘤病50例。在98篇文献报道的对696例患者进行的肾脏超声检查、51篇文献报道的对221例患者进行的肾脏CT检查和2篇文献报道的对2例患者进行的肾脏MRI检查中共发现肾脏血管平滑肌脂肪瘤416例;在58篇文献报道的对586例TSC患者进行的肝脏超声检查、30篇文献报道的对104例患者进行的腹部CT检查、2篇文献报道的对3例患者进行的腹部MRI检查中共发现肝脏血管平滑肌脂肪瘤141例。在诊断标准中的次要指征的报道中,对多发性肾囊肿的报道最多,而对牙釉质凹陷、Confetti皮损的描述却几乎缺失。在其他临床表现的研究中,癫痫的相关文献最多,有关智力评估的文献尚缺乏客观的智力评估标准。遗传学基因检测逐渐成为近几年文献报道的热点。结论:在过去13年间,中国医生对TSC的诊治作出了很大贡献,但诊断过程中仍存在对疾病认识的不足和对全局观念的缺乏,推广新版指南的诊断标准对于中国医生是十分有意义的。     

经皮肝穿刺胆道引流术与逆行胰腺胆管造影术对结石性梗阻性黄疸患者的疗效比较研究

目的:比较经皮肝穿刺胆道引流术(PTCD)与逆行胰腺胆管造影术(ERCP)对结石性梗阻性黄疸患者的治疗效果。方法:选取海军军医大学第三附属医院东方肝胆外科医院于2016年3月～2018年4月间收治的结石性梗阻性黄疸患者80例。按照介入治疗术式的异同将患者分为ERCP组(n=40,给予ERCP治疗)和PTCD组(n=40,给予PTCD治疗),记录两组手术时间、术中出血量、住院费用、住院时间、治疗成功率、黄疸缓解率、并发症发生情况,比较两组术前、术后1 d、术后7 d肝功能指标情况。结果:两组患者手术时间、术中出血量、治疗成功率、黄疸缓解率比较差异无统计学意义(P0.05),ERCP患者住院费用少于PTCD组患者,住院时间亦短于PTCD组患者(P0.05)。两组患者术后1 d、术后7 d丙氨酸转氨酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)水平均较术前降低,且两组患者术后7 d上述指标水平低于术后1 d(P0.05),ERCP组术后1 d、术后7 d ALT、TBIL、DBIL水平与PTCD组比较差异无统计学意义(P0.05)。两组患者术后并发症总发生率比较差异无统计学意义(P0.05)。结论:PTCD、ERCP治疗结石性梗阻性黄疸,均能有效改善患者临床症状和肝功能,且手术安全性相当,但ERCP可明显减少住院时间和住院费用。     

Feeding strategies for <Emphasis Type="Italic">E. coli</Emphasis> fermentations demanding an enriched environment

The addition of a carbon nutrient feed to a fed-batch cultivation is often not enough to obtain satisfactory growth and/or production. In some cases, an additional feed with for example supplementary amino acids or complex media is required. This work presents the development of feeding strategies where more than one feed is required and the knowledge of the growth requirements is low. Simulations and cultivations with E. coli are shown using the proposed feed controllers which are based on a probing control concept. The strategies work well and they can be used to shorten the process development phase considerably.     

Laws, constraints, and the modeling relation--history and interpretations

The modeling relation and models of complex systems expressed by non-integrable constraints were developed during ca. 1970-1987, when I worked most closely with Robert Rosen. I contrast the modeling relation within the organism itself as a necessary condition for life and evolution, as Rosen developed it in his fundamental work 'Anticipatory Systems', with the modeling relation within our brain as a necessary condition for understanding life, as Rosen developed it in 'Life Itself'. Our approaches to the modeling relation were complementary. Rosen focused on the formal relational conditions necessary for life, and on the limitations that formal mathematical-symbol systems impose on our models. I focused on the physical conditions necessary for these abstract relations to be realized, and on the symbolic control in organisms that allows open-ended evolution. I contrast Rosen's views on physics and evolution in 'Anticipatory Systems' and later papers with his views in 'Life Itself', and I speculate on why they differ so greatly.     

可视化多镜联合治疗复杂鹿角结石的对比研究

摘要 目的：研究不同组合方式治疗复杂鹿角样结石的疗效对比。方法：选取 80例我院治疗的复杂鹿角样结石患者,将患者随机分成两组,A组以经皮肾镜 +针状肾镜 （needle-perc） 的方式清理结石,B组以经皮肾镜 +输尿管软镜（flexibleureteroscope,F-URS）的方式清理结石,术后收集患者相关数据包括穿刺时间,单次穿刺成功率,单位结石量手术时间,清石效率,术中出血量,术后并发症,完全清石率等参数评估手术效果。结果：80例患者一期完成,主通道穿刺时间 A组（6± 1.62）min小于 B组（10±3.25）min（P<0.001）。单次穿刺成功率 A组（38/40）优于 B组（32/40）（P<0.05）。主通道清石时间 A组（40.94± 8.09）min和 B组（37.29± 4.19）min相比较无统计学意义（P>0.05）。残石处理时间 A组（34.37± 6.68）min小于 B组（49.55± 11.62）min（P<0.05）,主通道结石清石效率 A组（0.27± 0.05）cm3/min和 B组（0.26± 0.06）cm3/min相比较无统计学意义（P>0.05）,残石清石效率 A组（0.05± 0.01）cm3/min高于 B组（0.03± 0.01）cm3/min（P<0.05）。术后并发症及完全清石率两组无统计学意义（P>0.05）。结论：作为标准通道的辅助手段,needle-perc和输尿管软镜能很好的完成残石的处理,同超声定位穿刺相比较,可视穿刺花费时间更短,穿刺单次穿刺成功率更高,相对于软镜处理残石,needle-perc有更高的清石效率。两种方法的术中及术后并发症发生率,完全清石率无差别。