TGR5,expressing in many tissue cells,is a kind of bile acid membrane receptor and participates in a variety of metabolic and immune diseases.Activated TGR5 can keep the metabolism system in a steady state by mediating the metabolism of bile acid,lipid,and blood sugar,reducing insulin resistance and increasing the body's energy consumption; TGR5 could regulate the immune responses of mononuclear cell and Kupffer cell in the liver.For example,it can regulate the adaptive immune response by inhibiting the expression and release of inflammatory cytokines in Kupffer cells,and regulating the differentiation and maturation of dendritic cells.This review mainly focused on the function of TGR5 in liver metabolism and immune and further explored the related mechanism,as well as its clinical significance in related liver diseases.

Objective To investigate the role of autophagy in podocyte damage,and the intracellular mechanism of autophagy activation through passive Heymann nephritis (PHN) animal model.Methods Male Sprague-Dawley rats (n=40) were studied on day 0,2,4,7,and 21 after induction of PHN by injection of anti-Fx1A.Podocyte morphology and autophagosomes were observed by transmission electron microscopy.Podocyte numerical density was estimated by Weibel-Gomez =method.Cell apoptosis was detected by TUNEL assay and caspase-3 immunohistochemical staining.Expressions of autophagy markers and endoplasmic reticulum stress (ERS)-associated proteins were analyzed by Western blotting.Results (1) In PHN rats,immunohistochemical staining showed that C5b-9 deposited along glomerular basement membrane on day 4 to day 21.Small subepithelial electron -dense deposits and a part of foot process fusion were detected in the glomerulus of PHN rats on day 4 by transmission electron microscope,and podocyte damage was aggravated on day 21.Furthermore,compared with control,the urinary protein levels of PHN rats began to increase on day 3,and reached the top on day 21 [(50.6±6.0) mg/24 h].(2) The number of podocytes significantly decreased in PHN rats compared with control group on day 21(P ＜ 0.05).(3) In PHN rats,apoptotic podocytes were found by caspase-3 immunohistochemical staining and TUNEL assay on day 21.(4) The expression of autophagy marker LC3 Ⅱ was markedly increased on day 7 and 21,but down-regulated on day 21 compared with day 7.Moreover,accumulated autophagosomes in podocytes were detected on day 7 and 21 by transmission electron microscope.(5) The level of GRP78 was significantly increased on day 2 and 7 but reduced to baseline on day 21.At the same time,the downstream pathways (ATF6α,p-PERK and p-JNK) of unfolded protein response were also up-regulated in the early process of PHN and down-regulated later.Conclusions Autophagy is an important way to protect against immunemediated podocyte injury in membranous nephropathy.Autophagy activation is mainly related to endoplasmic reticulum stress induced by complement attack.This provides an important basis for a thorough understanding of the role of autophagy in the process of podocyte damage and the pathogenesis of membranous nephropathy.

Objective To investigate the value of intravital fluorescence microscopy in the observation of the changes of hepatic microcirculation in the rat model with hepatic cirrhosis and portal hypertension.Methods Seventy male SD rats were selected.According to the random number table,40 SD rats were randomly divided into the sham operation group,bile duct ligation (BDL) 2 weeks group,4 weeks group and 6 weeks group,there were 10 rats in each group,and the hepatic microcirculation of the rats was observed with intravital fluorescence microscope; the remaing 30 SD rats were randomly divided into the normal saline (NS) group,endothelin-1 (ET-1) group and the S-nitrosoglutathion (GSNO) group at 4 weeks later after the establishment of BDL model.The changes of hepatic microcirculation of the 3 groups were observed.All data were analyzed using the one-way analysis of variance (ANOVA) or paired samples t test.Results Nine rats died in the BDL model groups,and the survival rate was 85.0％ (51/60).All rats in the sham operation group were survived.The hepatic sinusoid diameters were decreased as time passed by.The hepatic sinusoid diameters of the BDL 2 weeks group,4 weeks group and 6 weeks group were (13.6 ± 1.0) μm,(8.8 ± 0.7) μm and (8.0 ± 0.5) μm,respectively,which were significantly shorter than (17.4 ± 1.0) μm of the sham operation group (t =5.86,18.24,15.57,P ＜ 0.05).The hepatic sinusoid densities of the BDL 2 weeks group,4 weeks group and 6 weeks group were (6.8 ±0.8)/ 200 μm,(4.3 ± 1.8)/200 μm and (4.0 ± 1.2)/200 μm,which were significandy lesser than (8.8 ± 0.5)/200 μm (t =3.25,2.77,2.12,P ＜ 0.05).At 15 minutes after injection of NS,the hepatic sinusoid diameter of the NS group was (7.2 ± 1.2) μm,which was significantly different from (6.9 ± 0.5) μm before injection of NS (t =0.89,P ＞ 0.05) ; the hepatic sinusoid density of the NS group before and after injection of NS were (6.6 ± 0.4) / 200 μm and (6.8 ± 1.4)/200 μm,with no significant difference(t =1.12,P ＞0.05).At 15 minutes after injection of ET-1,the hepatic sinusoid diameter of the ET-1 group was (5.4 ±0.5) μm,which was significantly different from (7.9 ± 0.6) μm before injection of ET-1 (t =7.39,P ＜ 0.05) ; the hepatic sinusoid density of the ET-1 group before and after ET-1 injection were (5.8 ± 1.2)/200 μm and (5.4 ± 1.8)/200 μm,with no significant difference(t =0.84,P ＞0.05).At 15 minutes after injection of the GSNO,the hepatic sinusoid diameter of the GSNO group was (11.4 ± 1.3) μm,which was significantly different from (7.5 ± 1.7) μm before injection of GSNO (t =5.95,P ＜ 0.05) ; the hepatic sinusoid density of the GSNO group before and after GSNO injection were(5.6 ± 0.8)/200 μm and (6.4 ± 1.6)/200 μm,with no significant difference (t =0.54,P ＞ 0.05).Conclusions The changes of hepatic microcirculation observed under intravital fluorescence microscope could reflect the progress of hepatic cirrhosis,and the changes of hepatic sinusoid diameters caused by drugs could be dynamically monitored under the intravital fluorescence microscope.

Objective To observe any differences in the morphology of the lumbar multifidus (LM) muscles between normal subjects and persons with chronic lumbar disc herniation (CLDH).Methods Thirty-two persons with CLDH and thirty-five matched,healthy controls performed various maneuvers in prone lying.Ultrasound imaging was used to measure the antero-posterior diameter (A-P),lateral diameter (Lat),cross sectional area (CSA) and flattening ratio (FR) of the bilateral LM muscles at the L4/5 level.Results In the control subjects,A-P,Lat,CSA and FR were not significantly different between the left and right sides.In those with CLDH,A-P,Lat and CSA were significantly smaller on the painful side than on the no-pain side,and this difference showed asymmetry between the two sides.Average A-P,Lat,FR and muscle CSA were all significantly smaller among the CLDH subjects on both sides compared with the controls.Conclusion CLDH induces asymmetric local atrophy of the bilateral multifidus muscles which can be detected and measured using ultrasound.

Objective: To investigate the clinical features and reliable diagnostic method in HIV/AIDS patients with smear negative pulmonary tuberculosis (TB). Methods: Clinical data of 112 HIV/AIDS patients complicated with smear negative pulmonary TB who were treated in our hospital from January 2013 to September 2015 were retrospectively analyzed. These clinical data includeded clinical symptom, blood routine test, blood biochemistry, T lymphocyte subsets classification, sputum acid-fast bacillus smear, mycobacterium tuberculosis culture, purified protein derivatives tuberculin (PPD) test, interferon gamma-release assay for Mycobacterium tuberculosis (T-SPOT.TB), TB-DNA and chest computed tomography (CT). Diagnostic specificity and sensitivity of these parameters were analyzed. Results: No specific clinical manifestation of these patients was identified. The chest CT feature was also atypical. The positive rates including T-SPOT, TB, TB-DNA and PPD test were all low. The positive rates of T-SPOT.TB and PPD test in patients with a CD4+ cell count >200 cells/μl was significantly higher than that of patients with a CD4+ cell count ≤50 cells/μl and 51≤CD4≤200 cells/μl (P<0.01). Conclusions The clinical feature of smear negative pulmonary TB in HIV/AIDS patients is atypical. For a definite diagnosis, a comprehensive analysis with clinical manifestations, laboratory test, imaging examination and etiologic detection is required.

Objective:To evalte a novel laparoscopic splenic artery ligation plus devascularization (LSALD) vs. laparoscopic splenectomy and devascularization (LSD) for the treatment of portal hypertention. Methods:From Jan 2014 to Dec 2019, 50 patients undergoing LSALD and 30 patients receiving LSD . We compared the safety and feasibility between LSALD and LSD groups by analyzing the patients′ blood routine, liver function before and after operation, intraoperative condition, postoperative recovery and prognosis.Results:The operation time[(181±72)min vs.(284±72)min , t=-6.205, P<0.01], intraoperative blood loss[(100±50)ml vs.( 700±86 ml), t=-5.166, P<0.01]and blood transfusion rate (28% vs.67%, χ 2=11.471, P<0.01)in LSALD group were significantly more favorite than those in LSD group ( P<0.05). The postoperative exhaust in the LSALD group was earlier than that in the LSD group (2 d vs.3 d, Z=2.361, P<0.05) though the WBC and blood platelet count was higher in LSD group ( P<0.05). Portal vein thrombosis occurred in 10 cases in LSD group and 6 cases in LSALD group (χ 2=5.757, P<0.05). Conclusion:Compared with laparoscopic splenectomy combined with periesophagogastric devascularization, laparoscopic splenic artery ligation combined with periesophagogastric devascularization is less traumatic, helping quick recovery and lower rate of post-op portal vein thrombosis.

Objective To compare the applicability of the Beijing Version of the Montreal Cognitive Assessment (MoCA) and the Mini Mental State Examination (MMSE) in screening for cognitive impairment in patients with acute ischemic stroke for 2-3 weeks.Methods MoCA and MMSE were conducted in 201 patients with acute ischemic stroke within 2 to 3 weeks after the onset of stroke.With MoCA＜23 and MMSE ＜26 as the cut off value,we assessed the clinic effect of the MoCA and MMSE and explored the correlation between two instruments.Results The average scores of MoCA and MMSE scale were (20.5±4.3) and (25.4±3.5) points.The prevalence of cognitive impairment evaluated with MoCA and MMSE were 57.2％and 43.3％,respectively.MoCA showed significant correlation with MMSE score (Pearson's correlation coefficient=0.833,P＜0.001),and an agreement with Kappa values of 0.532 (P＜0.01) in screening for cognitive impairment.Conclusions The prevalence of cognitive impairment assessed with MoCA is higher than that of with MMSE when using MoCA＜23 and MMSE＜26 as the cut off values.Both instruments show a good agreement for screening cognitive impairment in acute ischemic stroke within 2 to 3 weeks following the disease onset.

Objective:To explore the effect of grief counseling for relieving donor family′s grief. Methods:From September 2012 to February 2015, 180 families of potential organ donors, who met the class III standard of China, were invited to participate in this study. The grief score was evaluated using questionnaire before and after grief counseling. Results:All of 180 potential organ donor′s families had different level of sadness. The grief was significantly reduced after grief counseling and the score was significantly lower than before ( P<0 . 05 ) . Sixty-five cases agreed to donate organ and 60 cases succeed. Conclusion:Grief counseling for potential organ donor′s families could relieve their grief effectively. This method is beneficial for communication of organ donation and pro-moting donation career of China.

Objective To evaluate the safety and feasibility of simple ligation and resection of the tumor involved inferior vena cava (IVC) without reconstruction during the resection of huge intraabdominal tumors.Methods From 2008 to 2011,4 cases of giant tumor encroaching on inferior vena cava underwent resection without IVC reconstruction.After resection,renal vein was not obstructed in patient 1 and 2.Tumor invaded the third patient's retrohepatic inferior vena cava,anastomosis was performed between the left hepatic vein and the opening of atrium dextrum with artificial vascular graft.The forth patient had right trisegmentectomy of the liver with retrohepatic inferior vena cava resection,anastomosis was performed between the left hepatic vein and the remaining inferior vena cava.Results All 4 patients had a successful operation without intraoperative massive bleeding and death.The postoperative complications included edema in one patient whose collateral circulation was damaged and bile leak in one.Ewin sarcoma patient died of tumor recurrence after a year,but there was no sign of poor renal function and other complications.Ligament fibroma patient had lower limb edema for a long time after the surgery,and tumor relapse for the fourth time in two years following resection.Conclusions When a giant tumor involving and invading IVC,undergoing resection,under the condition that the collateral circulations around IVC established completely,resection and ligation of the inferior vena cava along with huge tumor without IVC reconstruction is safe.This method saves operation time,increases the safety of surgery.

Objective To determine the effect of rapamycin on sublytic C5b-9-induced podocyte adhesion damage,and whether autophagy is involved in this progression.Methods Sublytic complement C5b-9 stimulation was used in vitro.Autophagosomes were viewed using electron microscopy.Western blotting was used to measure the change of autophagy-related markers.Attachment assay was used to assess the adhesion of podocyte.Confocal microscopy was used to explore the expression patterns of cytoskeletal protein F-actin.Flow cytometry was used to measure the level of adhesion-associated protein integrin α3.Results (1) For ensuring sublytic complement injury,the maximal amounts of anti-podocyte antiserum and 160×-diluted normal human serum were used without inducing cell lysis (defined as ＞ 5％ LDH release).(2) Sublytic C5b-9 promoted autophagy in podocyte in vitro.The proautophagic effect of sublytic C5b-9 manifested in the form of accumulated autophagosomes and enhanced expression of LC3-lⅡ.(3) Inhibition of autophagy by 3-methyadenine enhanced the effect of sublytic C5b-9-induced podocyte injury,including serious cytoskeleton damage and markedly reduced adhesion of podocyte.(4) Rapamycin treatment significantly improved the above lesions.(5) Rapamycin enhanced autophagy induced by sublytic C5b-9 in podocyte.Conclusions In summary,rapamycin can improve sublytic CSb-9-induced podocyte adhesion damage by appropriate autophagy activation.These findings provide important information for the development of appropriate protocols for the application of mTOR (mammalian target of rapamycin) inhibitors in podocytopathy.