摘要:目的: 研究蛻皮甾酮對非酒精性脂肪性肝病大鼠模型腫瘤壞死因子α(TNFα)與核因子κB(NFκB)表達的影響，并探索其可能的作用機制。 方法 :健康成年SD大鼠36只,隨機分為正常對照組12只與實驗組24只;正常對照組喂以普通基礎飼料,實驗組應用高脂飼料喂養。實驗12周末時將造模成功的實驗組大鼠隨機分為模型組與蛻皮甾酮治療組2個亞組,每組12只;正常對照組喂以普通基礎飼料至16周,模型組繼續應用改良高脂飼料喂養至16周,蛻皮甾酮治療組大鼠在高脂飲食同時加用蛻皮甾酮灌胃。實驗16周末時處死3組所有大鼠;檢測肝臟指數,血清與肝組織生化指標及肝組織病理改變;ELISA法檢測肝臟TNFα水平;免疫組化檢測各組大鼠肝組織中核因子κB蛋白表達情況。 結果 :蛻皮甾酮治療組血清膽固醇(TC)、丙氨酸氨基轉移酶(ALT)和天門冬氨酸氨基轉移酶(AST)明顯低于模型組(212±058比263±024,Plt;005;5336±1848比8460±3627,P＜005;14020±3595比24359±3638,P＜001);蛻皮甾酮治療組與模型組相比肝組織丙二醛(MDA)水平降低明顯(18454±1645比23928±2376,P＜001),超氧化物歧化酶(SOD)活力增加顯著(942±052比518±043,P＜001),肝臟指數顯著降低(435±037比504±046,P＜001)，肝組織脂肪變性程度和炎癥活動度明顯減輕(546±037比630±049,P＜001)。蛻皮甾酮治療組與模型組相比TNFα與核因子κB水平明顯減輕(4304±748比6156±727,2465±539比4504±746,P值均＜001)。 結論 :蛻皮甾酮具有改善高脂飲食誘發的非酒精性脂肪性肝病大鼠肝臟酶學功能,通過增加肝組織SOD的含量和減少MDA的含量來減輕肝組織氧化應激水平,減輕肝組織TNFα和核因子κB來減輕肝臟炎癥,發揮防治非酒精性脂肪性肝病的作用。Abstract: Objective: To investigate the effect and possible mechanism of ecdysterone on the expression of tumor necrosis factoralpha (TNFα) and nuclear factor κ B (NFκB) in rats with nonalcoholic fatty liver disease of rats. Methods : A total of 36 male Sprague Dawley rats were randomly divided into two groups, who were fed with highfat diet (experimental group, n=24) and normal basic food (normal control, n=12) respectively. At the end of the 12th week, the experimental group was randomly divided into two subgroups: model group and ecdysterone group, each group contained 12 rats. From the 13th week, the rats in the normal control group and model group were lavaged with normal sodium, and the rats in the ecdysterone group were lavaged with ecdysterone at 10 mg·kg-1·d-1. At the end of the 16th week, all rats were weighed, narcotized, sacrificed, and the liver index, biochemical indicators in serum and liver tissues and the hepatic pathological changes were observed. The expression of TNFα was detected by ELISA and the expression of NFκB was measured by immunohistochemical staining. Results : At the end 16th week in ecdysterone group, the serum levels of cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reduced markedly (212±058 vs 263±024 and 5336±1848 vs 8460±3627, both P＜005; 14020±3595 vs 24359±3638, P＜001); the tissue content of malondialdehyde (MDA) was decreased evidently (18454±1645 vs 23928±2376, P＜001), while the activity of superoxide dismutase (SOD) was enhanced notably (942±052 vs 518±043, P＜001); the liver index was decreased significantly in comparison with that inmodel group (435±037 vs 504±046, P＜001); the degree of fatty degeneration and inflammation were relieved dramatically (546±037 vs 630±049, P＜001). The expression of TNFα and the levels of NFκB were significantly lower (4304±748 vs 6156±727 and 2465±539 vs 4504±746, both P＜001) in ecdysterone group compared with model group. Conclusion : The effects of ecdysterone in preventing NAFLD in rats could be related to the increase of SOD content in hepatic tissue and the decrease of MDA content, tumor necrosis factorα and NFκB.
【Abstract】Objective To introduce the birth and development of model of endstage liver disease (MELD) and evaluate its effect on liver transplantation(LT) as a new scoring system. Methods Literatures of MELD applied in LT were analyzed retrospectively. Results MELD scoring system was used for predicting the prognosis of patients with endstage liver disease and the death risk of candidates on waiting LT extensively and the order of organ sharing was determined by its predicable results. Conclusion MELD has been had a successful initial implementation for predicting the shortterm survival probability and mortality in patients with endstage liver disease, and meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, which has been proven to be a powerful tool for auditing the liver allocation system.
ObjectiveTo summarize the research progress of phytochemicals in the prevention and treatment of alcoholic liver disease and its possible clinical application value.MethodThe current literatures about the preventive and therapeutic effects of phytochemicals on alcoholic liver disease at home and abroad were reviewed.ResultsPhyto- chemicals could prevent and treat alcoholic liver disease by reducing inflammation, reducing oxidative stress, and improving lipid metabolism. They had the advantage of multi-targets.ConclusionPhytochemicals play an important role in the prevention and treatment of alcoholic liver disease, and it also lay a solid foundation for translational medicine.
ObjectiveTo summarize the changes of gut microbiota after cholecystectomy, the mechanisms of changes, and the relation with colorectal cancer, nonalcoholic fatty liver disease and post-cholecystectomy syndrome after cholecystectomy, in order to provide new ideas for the perioperative management of patients undergoing cholecystectomy. MethodThe studies related to gut microbiota after cholecystectomy at home and abroad were searched and analyzed for review. ResultsThe cholecystectomy disrupted the liver–bile acid–gut flora axis of the patients, and the composition and diversity of the gut microbiota of the patients were altered, and the alteration might lead to the occurrence of colorectal cancer, nonalcoholic fatty liver disease, and post-cholecystectomy syndrome, but the exact mechanism remained unclear. ConclusionsThe balance of intestinal microecology is disrupted after cholecystectomy, and the relation between cholecystectomy and gut microbiota may provide new ideas for the perioperative management of cholecystectomy patients and the prevention and treatment of diseases or symptoms after cholecystectomy, but the effect of cholecystectomy on gut microbiota and the relation with diseases or symptoms still need to be further studied.
Objective
To understand and analyze technique development of magnetic resonance elastography (MRE) and its application in chronic liver disease.
Method
The relevant literatures about the application of MRE in the field of chronic liver disease were reviewed.
Results
The liver fibrosis was a common pathway of chronic liver disease, which would progress to cirrhosis of the liver if untreated. The diagnosis and assessment of fibrosis was important in the treatment of patients with chronic liver disease. The liver biopsy was considered to be the reference standard for clinical assessment of liver fibrosis. However, this technique was invasive and still had inevitable drawbacks in the clinical practice. With the update of the imaging technology and equipment, the MRE had been developed as a safe and noninvasive examination method for the evaluation of liver fibrosis in the chronic liver disease, early diagnosis of nonalcoholic fatty liver disease, evaluation of focal liver lesions, and other clinical applications.
Conclusion
MRE is currently regarded as an attractive noninvasive technique in management of chronic liver disease.
ObjectiveTo summarize the epidemiology of nonalcoholic fatty liver disease (NAFLD) and the epidemiological and economic burdens of NAFLD, so as to provide a reference for hospital management decision-making. MethodThe domestic and foreign guidelines relevant to NAFLD and the literatures relevant to epidemiological investigation and disease burden researches were summarized and its research progress was reviewed. ResultsThe global prevalence of NAFLD was increasing over years. The incidence, mortality, and disability adjusted life years of liver cirrhosis and liver cancer caused by NAFLD had increased year by year. The patients relevant to NAFLD of inpatients and outpatients had increased obviously, and the overall medical expenses had also shown a rising trend. The possible reasons were health care awareness, new drug research, population aging, and excessive medical consumption. In addition, children and adolescents with NAFLD had a obviously increased risk of liver or extrahepatic diseases. ConclusionsBy understanding the epidemiological trend of NAFLD, it is a certain understanding of the disease burden of NAFLD and the related factors affecting the increase of its treatment cost. It is believed that it is necessary to further pay attention to and strengthen the genetic characteristics, pathogenesis, drug research and development, and early diagnosis of cirrhosis and liver cancer relevant to NAFLD in the future. At the same time, the NAFLD group of children and adolescents should not be ignored.
Non-alcoholic fatty liver disease (NAFLD) is one of the major chronic liver diseases that endanger human health. It is characterized by hepatic steatosis and absence of other causes of hepatic fat accumulation, such as alcohol abuse. The incidence of NAFLD is increasing year by year. However, the pathogenesis is still undefined. Porphyromonas gingivalis is a major periodontal pathogen of various periodontal disease. Apart from affecting periodontal health, Porphyromonas gingivalis is also related to the incidence of many systemic diseases. In recent years, Porphyromonas gingivalis is considered to be a risk factor of NAFLD. In this paper, the relationship between NAFLD and Porphyromonas gingivalis, as well as the possible pathogenesis are discussed.
ObjectiveTo analyze the incidence of bacterial lung infection after orthotopic liver transplantation and its risk factors.
MethodsNinety-six patients with end-stage liver disease who underwent liver transplantation from Jan. 2010 to Jun. 2012 in our hospital were retrospectively analyzed. The relationship of preoperative, intraoperative, and postoperative variables with early postoperative bacterial lung infection was explored by multivariate non-conditional logistic regression.
ResultsTwenty-nine cases of 96 cases after liver transplantation occurred early bacterial lung infection, and the infection rate was 30.21%(29/96), in which G-aerobic bacteria infection accounted for 65.52%(19/29), and G+ aerobic bacteria accounted for 34.48%(10/29). Preoperative model for end-stage liver disease score(OR=2.165, P=0.001), intraoperative blood transfusion(OR=1.952, P=0.003), average of plasma creatinine during 3 days after operation(OR=1.913, P=0.001), liquid negative balance time during 3 days after operation(OR=0.916, P=0.023), and postoperative hospital stay(OR=1.923, P=0.003) were all associated with early postoperative bacterial lung infection.
ConclusionsRetrograde reperfusion in orthotopic liver transplantation patients are susceptible to bacterial lung infections. Improving basic status before operation, controlling volume of intraoperative blood transfusion, the volume of transfusion, and postoperative hospital stay, and improving renal function can reduce incidence of early postoperative bacterial lung infection.
Objective
To investigate the changes of indocyanine green retention rate at 15 minutes (ICGR15) of autologous peripheral blood CD34+ hematopoietic stem cells transplantation in end-stage liver disease (end-stage liver, disease, ESLD) patients with different Child-Pugh grades during before and after transplantation of 3, 6, 12, 36, and 60 months.
Methods
The CD34+ hematopoietic stem cells transplantation were performed in 60 cases of advanced liver cirrhosis with different Child-Pugh grades who were ineffectively treated with strictly conservative treatment and complied with the criterion of liver transplantation. The ICGR15 were performed before transplantation and in 3, 6, 12, 36 and 60 months after transplantation. And the results of each time point in each Child-Pugh classification group were compared, and the rate of change of ICGR15 value were compared between each Child-Pugh classification group.
Results
The ICGR15 values of the Child-Pugh grading groups all decreased with time. In Child A group, there were respectively significant differences between the 6 months, 12 months, 36 months, and 60 months groups after transplantation and preoperative and 3 months groups after transplantation (P<0.05), but there was no significant difference between preoperative and 3 months group after transplantation (P>0.05), and there was significant difference between the 12 months and the 60 months group after transplantation (P<0.05). As same as Child A group, there were also significant differences between that time groups in the Child B group (P<0.05), but there were also significant differences between the 3 months group after transplantation and preoperative (P<0.05), and there were respectively significant differences between the 6 months and 12 months, 36 months, and 60 months group after transplantation in the Child B group (P<0.05). Also in the Child C group, there were significant differences between that time groups (P<0.05), but there was no significant difference between preoperative and 3 months group after transplantation (P>0.05), and there were respectively significant differences between the 6 months and 12 months, 36 months, and 60 months group after transplantation (P<0.05). There was no significant difference in the rate of ICGR15 between Child-Pugh classification groups.
Conclusion
Autologous peripheral blood CD34+ hematopoietic stem cells transplantation can effectively improve the liver function reserve capacity of ESLD patients and improve the safety of operation for a long time.
ObjectiveTo systematically review recent research advances in mesenchymal stem cells (MSCs) for preventing the progression of end-stage liver disease to hepatocellular carcinoma (HCC), with a focus on their mechanisms of action, clinical application prospects, and major challenges. MethodA systematic search of recent domestic and international literature was conducted, and the findings were summarized and reviewed. ResultsMSCs exert anti-hepatofibrotic effects through multiple pathways. First, via direct contact or paracrine signaling, MSCs inhibit the activation and proliferation of hepatic stellate cells (HSCs) and promote their apoptosis. Second, by releasing exosomes, MSCs deliver functional microRNA such as miR-455-3p, miR-4465, which target key signaling pathways including phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and Wnt/β-catenin, thereby suppressing the fibrogenic activity of HSCs. Concurrently, MSCs restore the balance between matrix metalloproteinases and their tissue inhibitors, promoting the degradation of excessively deposited extracellular matrix. Additionally, through the secretion of factors like vascular endothelial growth factor, MSCs improve hepatic microcirculation and oxygen supply, creating a favorable microenvironment for liver tissue repair. MSCs reshape the hepatic immune microenvironment to delay disease progression. By paracrine release of immunomodulatory factors such as prostaglandin E2 and indoleamine 2,3-dioxygenase, MSCs suppress the release of pro-inflammatory cytokines (such as tumor necrosis facto-α, interleukin-17) and promote the production of anti-inflammatory cytokines (such as interleukin-10). This modulates the functions of immune cells including T cells and macrophages, thereby alleviating hepatic inflammation. Notably, the immunomodulatory function of MSCs is highly plastic and heavily dependent on the status of the inflammatory microenvironment; under specific conditions, MSCs may also exert immune-promoting effects, highlighting the complexity of their functionality. Furthermore, MSCs and their exosomes demonstrate direct potential against HCC. MSCs can home to tumor sites and, by delivering anti-tumor molecules such as miR-17-5p or synergizing with drugs like sorafenib, inhibit HCC cell proliferation, induce apoptosis, and reverse drug resistance. Their mechanisms involve the regulation of key oncogenic signaling pathways, such as insulin like growth factor 1 receptor/PI3K/Akt and nuclear factor-κB. Meanwhile, MSCs may influence anti-tumor immune responses by modifying the tumor microenvironment. ConclusionsMSCs demonstrate significant potential in preventing the progression of end-stage liver disease to HCC primarily through multi-target and multi-mechanism synergistic actions, including anti-fibrotic, immunomodulatory, and direct anti-tumor effects. However, further standardization of their preparation and application protocols, optimization of clinical translation strategies, and validation of long-term safety and efficacy through high-quality clinical studies are still required.
