Immunotherapy for chronic hepatitis B / 临床肝胆病杂志

Although current direct anti-hepatitis B virus (HBV) drugs have good effects in controlling viral replication and limiting the progression to liver cirrhosis, there is still a long way to go in the treatment of chronic hepatitis B (CHB). Immune tolerance and immune dysfunction may be the two most important immunopathogenic factors. With reference to the development of new strategies and new drugs for anti-HBV immunotherapy and the latest research findings around the world, this article reviews the research advances in immunotherapy for CHB in recent years.

Expression of PPARαand Acox1 in Rats with Alcoholic Fatty Liver Disease / 华中科技大学学报(医学版)

Objective To investigate the molecular biological mechanism of deposition of triglyceride(TG)in hepatocytes in alcoholic fatty liver disease(AFLD)and the pathogenesis of this condition by detecting the contents of serum tumor necrosis fac-tor-α(TNF-α),liver triglyceride(TG),peroxisome proliferator-activated receptorα(PPARα)and acyl-CoA oxidase(Acox1)mR-NAs,and liver PPARαprotein after intervention with bezafibrate,a PPARαagonist.Methods Sixty Wistar rats were randomly divided into three groups:control group(n=20),AFLD group(n=20),and bezafibrate group(n=20).Animals in control group were given distilled water by gavage once a day for 8 weeks.Those in AFLD group were given ethanol and fish oil(2.5 mL/kg) by gavage daily for the same period of time.In bezafibrate group,rats were treated by gavage with ethanol and fish oil(2.5 mL/kg)for the first 4 weeks and then with bezafibrate(100 mg/kg)for another 4 weeks.TG in the liver was measured by colorimet-ric method,serum TNF-αlevels by enzyme linked immunoabsorbent assay (ELISA),the mRNA expression of PPARαand Acox1 in hepatocytes by reverse transcription polymerase chain reaction(RT-PCR)and the expression of PPARαprotein in hep-atocytes by Western blot.Results A significant increase in TG[AFLD group(0.72±0.09)mmol/L vs.control group(0.28± 0.07)mmol/L,P<0.01]and TNF-α[AFLD group(3.01±0.31)ng/mL vs.control group(1.07±0.28)ng/mL,P<0.01]was found in AFLD group when compared with control group.After bezafibrate intervention,the contents of liver TG and serum TNF-αwere significantly decreased.The mRNA expression of PPARα[AFLD group(0.22±0.08)vs.control group(0.68± 0.13),P<0.01]and Acox1[AFLD group(0.43±0.12)vs.control group(1.14±0.21),P<0.01]was suppressed in AFLD group,which was significantly reversed by bezafibrate treatment[bezafibrate group(0.59±0.13)for PPARαmRNA vs.AFLD group,P<0.01;bezafibrate group(0.83±0.17)for Acox1 mRNA vs.AFLD group,P<0.01].The expression of PPARαpro-tein in hepatocyts was also found to decrease in AFLD group[AFLD group(0.19±0.07)vs.control group(0.48±0.11),P<0.01].After bezafibrate intervention,it was profoundly increased.Conclusion The down-expression of PPARαand Acox1 in the liver of rats with AFLD may suppress the fatty acid metabolism and lead to the TG deposition in the liver.The increase in serum TNF-αcontents also contributes to the development of AFL.Bezafibrate can prevent and treat AFL by activating PPARα,increasing the expression of PPARαand Acox1 ,promoting the metabolism of fatty acids,decreasing the TG deposition and the serum TNF-αcontents.

Advances in Study on NLRP3 in Autoimmune Diseases / 胃肠病学

Inflammasome is a multi-protein complex which plays an important role in innate immune defense,and can adjust the activation of caspase-1 and promote the production of cytokines. NLRP3 is an important member of inflammasome Nod-like receptor(NLR)family,and its activation and expression occur mainly in macrophages and dendritic cells. NLRP3 can sense the pathogen associated molecular patterns(PAMPs)and damage associated molecular patterns(DAMPs)and initiate the inherent immune response,which plays an important role in the pathogenesis of autoimmune diseases. This article reviewed the advances in study on NLRP3 in autoimmune diseases.

Doctor-patient Communication Skills between Doctors and Hospitalized Patients / 中国医学伦理学

Good doctor-patient communication is the most effective way to build a harmonious doctor-patient relationship and reduce medical disputes, where the communication skill is the key. In communication with the hospitalized patients, it should pay attention to the communication object choice;the choice of the communicator;communication time, location and the form; pay attention to the communication protocol; using a comprehensible language communication;stand in the perspective of patients in order to enhance the doctor-patient trust and im-prove the doctor-patient relationship.

Influence of bone marrow mesenchymal stem cell transplantation on growth-associated protein-43 expression in rats with cerebral infarction / 中国组织工程研究

BACKGROUND:Growth-associated protein-43 is the primary substance for constructing plasticity of central nervous system, which is recognized as the first molecular marker for studying growth and repairing injury of nerves. OBJECTIVE: To explore the expression of growth-associated protein-43 in rats with focal cerebral ischemia following bone marrow mesenchymal stem cells (MSCs) transplantation.DEISNG, TIME AND SETTING: A randomized, controlled, animal study was performed at the Laboratory of Department of Neurology, Renmin Hospital of Wuhan University and Doctoral Scientific Research Work Station of C-BONS Pharmacy, Hubei, China, from March 2006 to October 2007.MATERIALS: Sixty adult Sprague Dawley rats, with clean grade, irrespective of genders, weighing (180±20) g, were randomly divided into the model, sham operated, and MSCs transplantation groups, with 20 animals in each group. METHODS: Additional 4 Sprague Dawiey rats, aged 2 months, were selected to isolate and culture MSCs, which was labeled with 5-Bromo-2,-deoxyuridine (BrdU). In the sham operated group, the right internal carotids were deligated after anaesthesia. The remained rats were prepared for models of right middle cerebral artery ischemia. At 24 hours after model preparation, 20 μL culture solution containing 5×105/L MSCs was injected into the left lateral ventricle of rats in the MSCs group, the same volume of phosphate buffer saline was injected in the model group.MAIN OUTCOME MEASURES: The rats were sacrificed prior to and at days 7, 14, and 21 after transplantation. The expression of growth associated protein-43 at the infarcted areas, the survival and migration of transplanted cells were examined by immunohistochemistry, at the same time, neurological deficit scores were recorded.RESULTS: The transplanted MSCs migrated from the left lateral ventricle to the infracted areas. Seven days after transplantation, the expression of BrdU-positive cells was found, reached a peak at day 14, and gradually decreased, until disappeared at 28 days after transplantation. Results of immunohistochemistry image analysis showed that immunological activity of growth associated protein-43 around the infarcted area of the MSCs group was obviously greater than that of the model group at days 7 and 14 after transplantation (P<0.06). There was no neurological deficit in the sham operated group. Moreover, with time prolonged, the neurological deficit scores gradually decreased in the model and MSCs groups, which were significantly lower in the MSCs group compared to the model group at day 14 after transplantation (P<0.05).CONCLUSION: MSCs transplantation up-regulates the expression of growth associated protein-43 around the infarcted area, which is consistent with the recovery of neurological function.

Effects and mechanism of changes of local neurotransmitters in rats' pylorus and bile reflux to the stomach with stress ulcer.

Stress ulcer occurs primarily in severe conditions, with a high incidence and mortality in intensive care units. However, studies on the association between stress ulcer and bile reflux to the stomach with stress ulcer are still inconclusive. Therefore, our research aimed to determine whether or not bile reflux exists during stress ulcer and then to investigate the effects and mechanism of changes of pyloric local neurotransmitters on bile reflux in such circumstances so as to provide a new pathway for clinical intervention. Cold water immersion was used to copy the stress ulcer model of rats. Sixty-five adult Sprague-Dawley rats of either sex were randomly divided into three groups: the normal control group (n = 10), the stress group (n = 30), and the antagonist group (n = 25). The gastric ulcer index, pH, and bile acid of gastric juice were measured before and after stress. Radio Immunoassay Detection Kit and Biochemic Detection Kit were used to measure local contents of CGRP (calcitonin gene-related peptide) and nitric oxide, respectively, in rats' pylorus. The local contents of nitric oxide in rats' pylorus reached a maximum at 1 hr after stress. The bile acid and pH of gastric juice peaked at 2 hr after stress and the ulcer index peaked at 4 hr after stress. But the local contents of CGRP in rats' pylorus decreased to the minimum at 4 hr after stress. The bile acid and ulcer index in the L-NAME group were significantly lower than in the antagonist control group. However, the bile acid in the hCGRP8-37 group was less than in the antagonist control group. Compared with hCGRP8-37 group, there was a significant reduction in bile acid in the L-NAME group. There was a significant reduction in the ulcer index of the hCGRP8-37 group compared with the L-NAME group and the antagonist control group. There was a certain kind of positive correlation between nitric oxide in rats' pylorus and bile acid to the stomach, for nitric oxide could loosen the pyloric sphincter and increase the bile acid to the stomach. L-NAME might reduce the local nitric oxide contents in rats' pylorus so that bile acid to the stomach might be decreased, obviously with a looser tight pyloric sphincter. Meanwhile, the CGRP in rats' pylorus was negatively associated with the ulcer index, hence CGRP might protect gastric mucosa under stress conditions.

The Effect of Chronic Stress on muc2 Protein Expression in Colonic Mucosa of Rats / 中国医师杂志

Objective To investigate the effect of chronic stress on the mucin secretion and muc2 protein content in goblet cells of rat colonic mucosa. Methods 24 healthy Wistar rats were randomly divided into 2 groups. Control group moved freely, experimental group was forced to undergo 2-hour-long immobilization stress per day for 14 days. The number of goblet cells containing mucus was determined by AB/PAS histochemical staining. The expression of muc2 protein was detected by immuohistochemical staining. Results Chronic stress decreased the number of goblet cells containing mucus, and down-regulated the expression of muc2 protein in goblet cells in rat colonic mucosa. Conclusion Chronic stress damaged the colonic epithelial barrier and functions of colonic goblet cells.