枯草杆菌肠球菌二联活菌胶囊对失代偿期肝硬化患者的保护作用

目的探讨枯草杆菌肠球菌二联活菌胶囊对失代偿期肝硬化患者的保护作用。方法 125例失代偿期肝硬化患者被随机分为观察组(63例)和对照组(62例)。对照组接受肝硬化常规治疗,观察组在对照组基础上加用枯草杆菌肠球菌二联活菌胶囊500mg/次,3次/d,口服。2组疗程均为2个月。观察两组患者治疗前后肝功能(ALT、TBil、PA)、血氨、血清内毒素、炎症反应因子(IL-6、TNF-α、CRP)、Child-Pugh分级变化及并发症发生情况。结果治疗后观察组ALT、TBil、血氨、血清内毒素、IL-6、TNF-α及CRP明显降低,PA明显升高(P0.01),对照组ALT、TBil、血氨、IL-6、TNF-α及CRP也明显降低(P0.05或P0.01);两组治疗后比较,观察组上述指标的改善情况优于对照组(P0.01);观察组Child-Pugh分级有明显改善(P0.01),但对照组治疗前后及两组治疗后ChildPugh分级差异无统计学意义(P0.05);观察组并发症SBP、HE、HRS的发生率明显低于对照组(P0.05)。治疗过程中未发现明显不良反应。结论枯草杆菌肠球菌二联活菌胶囊能降低失代偿期肝硬化患者的血氨、血清内毒素及炎症因子IL-6、TNF-α、CRP水平,改善肝功能,减少并发症的发生。     

乳果糖联合培菲康预防肝硬化自发性细菌性腹膜炎的疗效观察

目的 探讨乳果糖联合培菲康预防肝硬化自发性细菌性腹膜炎(SBP)的疗效.方法 选择肝硬化失代偿期患者186例,随机分为乳果糖与培菲康联合治疗组和常规抗生素治疗组各93例,住院期间同时予以护肝利尿及对症支持治疗,用药3个月进行观察,并采集腹水样本,采用ELISA方法进行TNF-α和IL-6的检测.结果 肝硬化患者应用乳果糖与培菲康联合治疗组SBP发生率为12.9％,而常规抗生素治疗组SBP发生率为21.5％,二者间比较差异有统计学意义(P＜0.05).SBP发生患者腹水TNF-α的水平为(1650±126) pg/mL,而未发生SBP为(1312±289) pg/mL,两组间比较差异有统计学意义(P＜0.05).SBP发生患者腹水IL-6的水平为(2566±138) pg/mL,而未发生SBP患者中为(924±251) pg/mL,两组间比较差异有统计学意义(P＜0.01).结论 肝硬化患者应用乳果糖联合培菲康可显著降低SBP的发生率.腹水TNF-α和IL-6的水平可监测肝硬化患者SBP的发生.     

地衣芽胞杆菌治疗肝硬化并自发性细菌性腹膜炎的临床疗效研究

目的观察益生菌治疗肝硬化自发性细菌性腹膜炎（SBP）患者的效果。方法将60例肝硬化自发性细菌性腹膜炎随机分成2组,对照组30例,予抗感染、保肝、降门脉高压、利尿、营养支持治疗;治疗组30例,在对照组的综合治疗基础上加用地衣芽胞杆菌胶囊,每日3次,每次2粒,连服21d后观察感染控制及肝功能变化情况。结果治疗组总有效率明显高于对照组,除了腹痛、腹部压痛无差异外,发热、腹泻消失、腹水常规、肝功能改善方面与对照组比较差异存在统计学意义（P〈0．05）。结论益生菌对肝硬化并发自发性腹膜炎有一定治疗效果。     

醋酸奥曲肽联合乌司他丁对重症急性胰腺炎患者血清ET、MCP-1、TNF-α、IL-6水平及预后的影响

目的:探讨醋酸奥曲肽联合乌司他丁对重症急性胰腺炎血清内皮素(ET)、单核细胞趋化因子蛋白1(MCP-1)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平及预后的影响。方法:纳入我院2017年1月至2018年9月收治的94例重症急性胰腺炎患者,并依据随机数字表法将其分为对照组47例与观察组47例。对照组患者给予乌司他丁治疗,观察组在对照组基础上结合醋酸奥曲肽治疗,两组疗程均为7～14 d。比较两组治疗的疗效,血淀粉酶和尿淀粉酶恢复正常时间,腹痛缓解时间、肠鸣音恢复时间和腹胀缓解时间,治疗前后血清ET、MCP-1、TNF-α、IL-6水平的变化及预后。结果:观察组治疗总有效率(93.62%)显著高于对照组(72.34%)(P0.05)。观察组血淀粉酶和尿淀粉酶恢复时间、腹痛缓解时间、肠鸣音恢复时间和腹胀缓解时间明显短于对照组(P0.05)。两组治疗后血清ET、MCP-1、TNF-α和IL-6水平均较治疗前降低(P0.05),且观察组以上指标均显著低于对照组(P0.05)。观察组出院时生存率高于对照组,但差异无统计学意义(P0.05)。结论:与单用乌司他丁相比,醋酸奥曲肽联合乌司他丁治疗重症急性胰腺炎患者疗效更好,其可显著降低患者血清ET、MCP-1、TNF-α和IL-6水平。     

双歧杆菌四联活菌片对肝硬化白发性细菌性腹膜炎患者肠黏膜屏障和炎症因子的影响

目的探讨双歧杆菌四联活菌片对肝硬化自发性细菌性腹膜炎（SBP）患者肠黏膜屏障和炎症因子的影响。方法选择乙肝后肝硬化SBP患者68例,分为治疗组和对照组。两组患者均予以低盐饮食、护肝利尿、补充白蛋白和抗感染等基础治疗。治疗组在此基础上予以双歧杆菌四联活菌片口服,1．5g／次,3次／d,连用6周。结果治疗6周后,两组血浆内毒素、PCT和尿L／M比值比较均有明显下降（对照组比较P〈0．05,或治疗组比较P〈0．01）,且治疗组下降幅度明显优于对照组（P〈0．05）;两组血浆TNF-α、IL-6和IL-10水平均有明显下降（对照组比较P〈0．05,或治疗组比较P〈0．01）,且治疗组下降幅度明显优于对照组（P〈0．05）。治疗组临床总有效率明显高于对照组（χ2=8．17,P〈0．01）,治疗期间未发生严重的药物不良反应。结论双歧杆菌四联活菌片治疗肝硬化SBP患者具有较好的临床疗效及安全性,对患者肠黏膜屏障功能具有良好保护和改善作用,并能下降血浆TNF—α、IL-6和IL-10水平,具有辅助治疗肝硬化作用。     

双歧三联活菌对肝硬化患者血浆中内毒素及多种细胞因子水平的影响

目的:初步探讨在常规保肝治疗的基础上辅助应用双歧三联活菌制剂治疗肝硬化内毒素血症的疗效,并观察治疗前后血浆中内毒素以及IL-1α、IL-6、TNFα等水平的变化.方法:选择典型肝硬化失代偿期患者60例,随机分为对照组和试验组.应用鲎试剂动态比浊法准确定量测定血浆中内毒素的含量;应用酶联免疫技术测定血浆中IL-1α、IL-6、TNF-α的含量.比较治疗前后组间和组内血浆中内毒素、IL-1α、IL-6和TNFα水平的变化.结果:试验组治疗后与治疗前相比,各观察指标的含量均明显降低(P<0.05);对照组治疗前后血浆中各观察指标的含量差异无显著性;治疗后试验组血浆中各观察指标的含量均比对照组低(P<0.05),差异有统计学意义.结论:常规保肝治疗的基础上辅助应用双歧三联活菌制剂贝飞达与单纯保肝治疗相比,可以明显降低肝硬化失代偿期患者血浆中内毒素的水平,减少生物活性介质IL-α、IL-6和TNFα的释放,促使肝功能好转,具有重要的临床实用意义.     

复合乳酸杆菌治疗肝硬化失代偿期患者效果分析

目的:探讨分析复合乳酸杆菌在治疗肝硬化失代偿期患者中的效果。方法:选择2011年1月~2014年12月间在我院住院治疗的54例肝硬化失代偿期患者为研究对象,随机分为观察组和对照组各27例,选取同时期健康体检者27例为健康对照组。观察组患者接受复合乳酸杆菌联合肝硬化常规治疗,对照组仅接受肝硬化常规治疗。治疗8周后,比较对照组和观察组治疗前后及健康对照组患者血浆ALT、AST、内毒素、IL-1β、TNF-α、血氨及消化道症状积分的差异。结果:观察组和对照组患者治疗前血浆ALT、AST、内毒素、IL-1β、TNF-α、血氨水平及消化道症状积分差异无统计学意义(P0.05),均明显高于健康对照组(P0.05);治疗后两组患者上述指标均明显降低(P0.05),但观察组较对照组下降更为明显(P0.05)。结论:复合乳酸杆菌联合常规疗法在肝硬化失代偿期患者的治疗方面发挥了重要作用,值得临床推广。     

益生菌对稳定性冠心病患者血清TMAO水平的影响及 与血清炎性因子水平的相关性

目的探究益生菌对稳定性冠心病(SCAD)患者血清氧化三甲胺(TMAO)水平的影响及其与血清炎性因子水平的相关性。方法选取我院2017年6月至2018年1月间诊断及治疗的SCAD患者74例,采用随机数表法分为益生菌组(37例)与对照组(37例),对照组予以稳定型冠心病标准治疗,益生菌组在对照组的基础上口服益生菌制剂,金双歧,2 g/次,3次/d,疗程均为2个月,比较治疗前后患者血液中TMAO、TNF-α、IL-6、IL-8、CRP水平及大便中双歧杆菌载量,使用Pearson相关性分析模型探究细菌载量与TMAO、TNF-α、IL-6、IL-8、CRP水平的相关性。结果治疗前两组TMAO、TNF-α、IL-6、IL-8及CRP水平无明显差异(Ps0.05),治疗后两组上述指标均显著下降(Ps0.05),其中益生菌组TMAO、TNF-α及CRP水平显著低于对照组(t=2.702,4.301,2.632;P=0.009,0.000,0.010)。治疗前两组患者大便中双歧杆菌载量无明显差异(P0.05),治疗后益生菌组双歧杆菌载量显著提高(t=4.382,P=0.000),且显著高于对照组(P0.05)。Pearson相关性分析显示,双歧杆菌载量与TMAO、TNF-α水平存在显著负相关(r=-0.706,-0.427;P=0.000,0.017)。结论益生菌可有效改善SCAD患者TMAO水平,其与TMAO、TNF-α水平呈显著负相关。     

控制性液体复苏治疗严重多发伤的疗效及其对血清炎症因子水平的影响

目的:观察控制性液体复苏治疗严重多发伤的疗效及其对降钙素原(PCT)、高敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)水平的影响。方法:选取2010年12月~2012年12月在我院就诊的多发伤患者64例,随机分为观察组和对照组,每组各32例,对照组予以快速液体复苏,观察组予以控制性液体复苏。观察和比较两组的复苏液体量、复苏1小时乳酸、复苏时间、确定手术时间、住院时间、治愈率和死亡率,以及入院时和治疗后患者的血清PCT、hs-CRP、IL-6和TNF-α水平。结果:治疗后,观察组的复苏液体量、复苏1h乳酸、复苏时间、确定手术时间、住院时间和死亡率较对照组明显降低或减少,而观察组的治愈率较对照组明显提高。两组治疗后血清PCT、hs-CRP、IL-6和TNF-α水平均较入院时明显降低(P0.01),且观察组以上指标的水平显著低于对照组(P0.01)。结论:控制性补液复苏对多发伤的疗效优于快速液体复苏,并可显著降低患者的血清PCT、hs-CRP、IL-6和TNF-α水平。     

乌司他丁联合阿托莫兰对感染性休克患者血清IL-6,TNF-α和PCT水平的影响

目的:探究乌司他丁联合阿托莫兰对感染性休克患者血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和降钙素原(PCT)水平的影响。方法:选择2013年6月~2015年12月期间我院收治感染性休克患者79例为研究对象;采用随机数字法将其分为观察组(39例)和对照组(40例),观察组患者给予乌司他丁联合阿托莫兰治疗,对照组给予常规抗感染治疗;观察并比较两组患者治疗前后IL-6、TNFα和PCT水平,比较两组患者药物不良反应、多器官功能障碍综合征(MODS)发生率及病死率。结果:治疗前两组患者间IL-6、TNF-α及PCT水平均无差异(P0.05);治疗后两组患者IL-6、TNF-α及PCT均显著下降,且观察组IL-6、TNF-α及PCT水平低于对照组(P0.05);治疗过程中两组患者药物不良反应发生率无差异(P0.05);治疗后观察组MODS及死亡发生率均低于对照组(P0.05)。结论:乌司他丁联合阿托莫兰能够改善对感染性休克患者炎症反应,降低机体IL-6、TNF-α及PCT水平,降低MODS发生率及病死率,在临床治疗感染性休克具有重要价值。     

Mitochondrial dysfunction in liver disease and organ transplantation

The mitochondria play a crucial role in maintaining hepatocyte integrity and functions. Mitochondrial defects are either inherited or acquired. Mitochondria dysfunction occurs when the hepatocyte experience excessive physiologic stress. Its clinical presentation depends on the severity of the stress. It varies from mild abnormalities in liver biochemical tests to manifestations of acute or chronic liver failure. Mitochondria dysfunction is implicated in most liver disease and in early graft dysfunction after liver transplantation. This review will address the role of mitochondria in liver disease.     

Uptake of phosphatidylserine-containing liposomes by liver sinusoidal endothelial cells in the serum-free perfused rat liver

We studied the kinetics of hepatic uptake of liposomes during serum-free recirculating perfusion of rat livers. Liposomes consisted of phosphatidylcholine, cholesterol and phosphatidylserine in a 6:4:0 or a 3:4:3 molar ratio and were radiolabelled with [³H]cholesteryl oleyl ether. The negatively charged liposomes were taken up to a 10-fold higher extent than the neutral ones. Hepatic uptake of fluorescently labelled liposomes was examined by fluorescence microscopy. The neutral liposomes displayed a typical Kupffer cell distribution pattern, in addition to weak diffuse staining of the parenchyma, while the negatively charged liposomes showed a characteristic sinusoidal lining pattern, consistent with an endothelial localization. In addition, scattered Kupffer cell staining was distinguished as well as diffuse parenchymal fluorescence. The mainly endothelial localisation of the negatively charged liposomes was confirmed by determining radioactivity in endothelial and Kupffer cells isolated following a 1-h perfusion. Perfusion in the presence of polyinosinic acid, an inhibitor of scavenger receptor activity, reduced the rate of uptake of the negatively charged liposomes twofold, indicating the involvement of this receptor in the elimination mechanism. These results are compatible with earlier in vitro studies on liposome uptake by isolated endothelial cells and Kupffer cells, which showed that in the absence of serum also endothelial cells in situ are able to take up massive amounts of negatively charged liposomes. The present results emphasize that the high in vitro endothelial cell uptake in the absence of serum from earlier observations was not an artifact induced by the cell isolation procedure.     

Role of liver stem cells in hepatocarcinogenesis

Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the “cancer stem cell hypothesis”, which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells (liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future.     

Potential neural progenitor cells in fetal liver and regenerating liver

From unfractionated embryonic mice liver cells, appreciable amount of spherical bodies containing nestin-positive cells were generated in the presence of neuronal growth factors. Following cultivation on poly-d-lysine/laminin-coated slips, approximately 70% of the cells expressed neuronal markers, and 16% had long processes. Functional analysis of these long-process-bearing cells with the whole-cell patch clamp method showed an inward current in response to glutamate, GABA, and serotonin as the neuronal characteristics. Furthermore, regenerating liver in adult mice also contained nestin-positive cells to the same extent as fetal liver. Regenerating liver could have potential as a source of neural cells for autologous transplantation.     

Expression of neuritin during liver maturation and regeneration

Cell surface molecules are not only important for cell-cell interactions but also useful for a marker to define cell types and differentiation stages. Unlike hematopoietic system in which numerous such antigens have been identified, only a few cell surface molecules have been used to define differentiation stage of hepatocytes. In order to identify such cell surface molecules, we performed DNA microarray analysis using mRNA from fetal hepatocytes in E12.5 and E17.5 mice and cDNAs encoding a membrane protein were selected. Northern blot analysis was employed to confirm the genes upregulated during maturation of fetal hepatocytes and neuritin, a GPI-anchored protein, was found as a membrane protein expressed in hepatocytes, but not in nonparenchymal cells. Its expression increased along with liver development and the maximum expression was achieved from the neonatal to adult stage. The neuritin protein was localized in sinusoidal lumen of hepatocytes in adult liver. Partial hepatectomy transiently downregulated the expression of neuritin. The expression of neuritin mRNA in C/EBPalpha deficient liver was reduced to about 50% of that of wild type mice. Thus, neuritin expression is well correlated to the maturation of hepatocytes and can be a useful tool to define the differentiation stage of hepatocytes.     

Ultrasound scatter-spacing based diagnosis of focal diseases of the liver

Ultrasound returns from liver shows periodicity arising from periodic scattering centers within tissue. Focal diseases such as tumors interrupt this structure. In this paper, we propose the use of a wavelet transform based technique to estimate the inter-scatterer-distribution (ISS) in diagnosing focal diaseases of the liver. The efficacy of the method is illustrated with simulated and clinical ultrasound images. The mean value (MSS) of the ISS has been proposed as a signature for focal diseases, but its effectiveness has not been established yet. We show that the ISS distribution may function as a feature to characterize focal diseases even when its mean value MSS fails. The method proposed in this paper works even when data is non-stationary.     

甲亢性肝损害116例临床分析

目的探讨甲状腺功能亢进症（甲亢）肝损害的临床特点。方法收集228例甲亢患者的临床资料,分为肝损害组及无肝损害组,对两组患者的年龄、性别、甲亢病程、肝功能及甲状腺功能等指标进行分析比较。结果 228例甲亢患者中发生肝损害116例,发生率为50.72%。甲亢患者的性别与甲亢性肝损害的发生率无相关性;而年龄越大甲亢性肝损害发生率越高,病程越长甲亢性肝损害发生率也越高。甲亢性肝损害患者甲状腺功能指标TT4、FT3明显高于甲亢肝功能正常的患者,差异有统计学意义（P〈0.05）;肝功能测定以ALT、ALP升高多见。结论甲亢性肝损害的发病率较高,病情的严重程度与年龄、病程、甲状腺激素水平有密切关系;建议临床医生对初诊及复诊甲亢患者进行肝功能常规测定,以便合理选用治疗方案,使甲亢性肝损害得以及早治疗。     

Proteomic analysis of liver tissues subjected to early ischemia/reperfusion injury during human orthotopic liver transplantation

Knowledge of early molecular events occurring upon ischemia/reperfusion (I/R) during liver transplantation (LT) is of great importance to improve the therapeutic intervention of surgical treatment. However, nowadays, few data are available on early protein targets of I/R injury. To identify these proteins, we used a differential proteomics approach in the characterization human liver biopsies during I/R upon LT. Analyses were performed on nine donor livers during LT. By using 2-DE and MALDI-TOF MS, we identified 36 proteins which resulted significantly altered upon I/R injury. The majority of these proteins are functionally involved in lipid and energy metabolism, in different metabolic pathways, in redox signalling and in oxidative-stress response. Our data represent the first global approach in the study of I/R injury in liver.     

Interleukin-6: A promising cytokine to support liver regeneration and adaptive immunity in liver pathologies

Liver pathologies (fibrosis, cirrhosis, alcoholic, non-alcoholic diseases and hepatocellular carcinoma) represent one of the most common causes of death worldwide. A number of genetic and environmental factors contribute to the development of liver diseases. Interleukin-6 (IL-6) is a pleiotropic cytokine, exerting variety of effects on inflammation, liver regeneration, and defence against infections by regulating adaptive immunity. Due to its high abundance in inflammatory settings, IL-6 is often viewed as a detrimental cytokine. However, accumulating evidence supports the view that IL-6 has a beneficial impact in numerous liver pathologies, due to its roles in liver regeneration and in promoting an anti-inflammatory response in certain conditions. IL-6 promotes proliferation, angiogenesis and metabolism, and downregulates apoptosis and oxidative stress; together these functions are critical for mediating hepatoprotection. IL-6 is also an important regulator of adaptive immunity where it induces T cell differentiation and regulates autoimmunity. It can augment antiviral adaptive immune responses and mitigate exhaustion of T cells during chronic infection. This review focuses on studies that present IL-6 as a key factor in regulating liver regeneration and in supporting effector immune functions and suggests that these functions of IL-6 can be exploited in treatment strategies for liver pathologies.