Determination of a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-associated acute-on-chronic liver failure / 临床肝胆病杂志

Objective To investigate a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and to realize accurate early diagnosis. Methods A retrospective analysis was performed for the clinical data of 1232 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from September 2008 to September 2018, and according to the baseline serum level of total bilirubin (TBil), the patients were divided into group A (TBil 15%) in patients with acute-on-chronic liver failure (ACLF). Although there was a difference in long-term mortality rate between the two groups, there was no significant increase in transplant-free mortality rate after 90 days in either group. Conclusion Under the premise of international normalized ratio ≥1.5, it is not recommended to increase the threshold of TBil to 205.2 μmol/L in the diagnostic criteria for HBV-ACLF, so as to ensure the early diagnosis of more ACLF patients and bring more opportunities for treatment and cure.

Clinical features of patients with acute-on-chronic liver failure and bacterial infection and influencing factors for prognosis / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of infection in patients with acute-on-chronic liver failure (ACLF) and bacterial infection and the influencing factors for 90-day survival rate. MethodsThe patients with ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to December 2015 were enrolled, and related clinical data were collected and analyzed, including infection time and site, microbial culture, biochemical parameters and inflammatory markers, and 28- and 90-day prognosis after infection. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The life-table method was used to plot survival curves. The indices affecting prognosis in the univariate analysis were further included in the multivariate logistic regression analysis. ResultsA total of 1074 patients with ACLF were admitted, among whom 609 had bacterial infection, and the incidence rate of bacterial infection was 567%. Among these 609 patients, 16 underwent liver transplantation within 90 days and related data statistics were obtained for the remaining 593 patients. As for infection site, among the patients with infection, 70.15% had abdominal infection, 41.15% had pulmonary infection, 11.97% had sepsis, 5.40% had urinary system infection, 4.89% had thoracic infection, and 8.6% had infection at other sites. Among the patients with infection, 64.76% had infection at a single site. The positive rates of microbial culture of ascites, phlegm, urine, and pleural effusion were 22.70%, 52.82%, 40.63%, and 35.71%, respectively. Escherichia coli was the most common bacterium in ascites and accounted for 43.82%; Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii accounted for 22.67%, 2400%, and 22.67%, respectively, in phlegm; Escherichia coli, Klebsiella pneumoniae, and Staphylococcaceae accounted for 33.80%, 29.58%, and 15.49%, respectively, in blood culture. The 90-day survival rate after infection was 38.11% (226/593) in the patients with ACLF, and the multivariate logistic regression analysis showed that age (P=0.006), stage of hepatic encephalopathy (HE) (P＜0001), stage of liver failure (P＜0.001), and acute kidney injury (AKI) (P＜0.001) were independent risk factors for 90-day survival in patients with ACLF and infection. ConclusionThere is a high incidence rate of infection in patients with ACLF. The 90-day survival rate is relatively low, and the presence of AKI, HE stage III or above, and advanced liver failure may indicate poor prognosis.

Association between blood ammonia and 90-day prognosis in patients with hepatitis B virus-related acute-on-chronic liver failure / 临床肝胆病杂志

ObjectiveTo investigate the association between baseline blood ammonia (BLA) and 90-day prognosis in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). MethodsA retrospective analysis was performed for the clinical data of 789 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to December 2016, and the association between baseline BLA and 90-day prognosis was analyzed. The Cox regression risk model was used for multivariate analysis. The Kaplan-Meier survival curve was used to analyze the 90-day survival rate of patients with different levels of baseline BLA, and the log-rank test was used for comparison. ResultsThe Cox multivariate regression analysis showed that BLA was independently and positively correlated with the risk of 90-day death in HBV-ACLF patients (Model 2: hazard ratio = 1.007, 95% confidence interval: 1.005-1.010, P＜0.00001). The log-rank test indicated that in the patients without hepatic encephalopathy (HE), the BLAhigh group had the highest 90-day cumulative mortality rate, followed by the BLAmid group and the BLAlow group (P=0002 3); among the patients with HE, the BLAhigh group had a significantly higher 90-day cumulative mortality rate than the other two groups (P=0.012), while there was no significant difference in 90-day cumulative mortality rate between these two groups (P=0.18). ConclusionBaseline BLA is independently and positively correlated with the risk of 90-day death in HBV-ACLF patients, and it may have a certain clinical value in treatment and prognostic evaluation.

The function and related factors between depression, anxiety and rheumatoid arthritis / 中华风湿病学杂志

Objective To survey the function and relation of cytokine interleukin-6 (IL-6) between depression,anxiety and rheumatoid arthritis (RA).Methods One hundred and twenty-one patients with RA were investigated.All of them were assessed by Hamihon Depression Rating Scale and Hamihon Anxiety Rating Scale.Results ① The rate of depression in RA patients was 44.6％,and the rate of anxiety was 32.2％,the rate of depression combined anxiety in RA patients was 30.6％.② Social factors:Unemployment [14 cases (26.4％) vs8 cases (11.9％),x2=4.14] and education [41 cases (83.7％) vs 37 cases (58.7％),x2=8.11]was significantly different between depression and non-depression patients (P＜0.05).Age,unemployment and education was significantly different between anxiety patients and non-anxiety patients (P＜0.05).③ Clinical factors:tender joint count,swollen joint count,disease activity score (DAS)28,health assessment questionnaire (HAQ),VAS,function of joint and C-reactive protein (CRP) was significantly different between depression patients and non-depression patients [6(2,21) vs 1(0,14);4(1,11) vs 2(0,8);24.0(2.5,36.25) vs 2.5(0,19.5);5(3,9) vs 4(0,7);89.8％ vs 9.7％;37.63(13.25,70.75) vs 11.29(2.05,36.78)] (P＜0.05).And anxiety patients and non-anxiety patients had the same results [6(3,25) vs 2(0,14);6(1.5,12) vs 2(0,7.25);25(5,36) vs 3(0,25);8(5,10) vs 5(1.75,7);91.4％ vs 64.5％;33.4(11.0,63.0) vs 16.8(2.5,54.3)](P＜0.05).④ Cytokine:IL-6 was significantly different between depression patients and non-depression patients (P＜0.05).JAK-2,JAK-3,Signal transducer and activator of transcription (STAT)-3,matrix Metalloproteinases (MMP)-3,MMP-13 were not different between depression patients and non-depression patients (P＞0.05).IL-6,JAK-2,JAK-3,STAT-3,MMP-3,MMP-13 were not different between anxiety patients and non-anxiety patients (P＞0.05).⑤ Correlation analysis:Education level was negatively related with the severity of depression (r=0.288,P＜0.05).Tender joint count,swollen joint count,DAS28,HAQ,VAS,function of joint,erythrocyte sedimentation rate (ESR),CRP,IL-6 was positively related with the severity of depression (r=0.348,0.268,0.481,0.318,0.381,0.417,0.397,0.311,0.249;P＜0.05).Education level was negatively related with the severity of anxiety.Tender joint count,swollen joint count (r=-0.244,P＜0.05),DAS28,HAQ,VAS,function of joint,ESR,CRP was positively related with the severity of depression (r=0.282,0.261,0.381,0.284,0.284,0.299,0.263,0.178;all P＜0.05).⑥ Risk factors:IL-6 was the only risk factor in RA patients with depression.Conclusion The rate of depression and anxiety in RA is 44.6％.Depression and anxiety is related with disease activity,pain and HAQ.IL-6 is a high risk factor that makes patients prone to develop depression in RA patients.

Effects of propofol anesthesia on cognitive function of aged rats / 国际生物医学工程杂志

Objective To investigate the effects of propofol anesthesia on cognitive function of aged rats. Methods Ninety-six male aged SD rats (16 months) were collected and given propofol anesthesia via tail vein catheter. At 7, 30, and 90 d after anesthesia, fear conditioning experiment was performed to test long-term memory of the aged rats (12 rats at each time point, total 36 rats). At 1, 2, 3, 4, and 5 d after anesthesia, spontaneous alternation in Y-maze experiment was performed to test spatial working memory of the aged rats (12 rats at each time point, total 60 rats). Results There were no statistical differences in long-term memory at 7, 30, and 90 d after anesthesia between the propofol group and control group (P>0.05). While spatial working memory of aged rats in propofol group was impaired at 1 and 2 d after anesthesia (P0.05). Conclusions These results indicate that clinical dose propofol anesthesia will not induce long-term memory impairment of aged rats, although it impairs spatial working memory of aged rats within 48 h after anesthesia.

The late stage of autophagy: cellular events and molecular regulation

Autophagy is an intracellular degradation system that delivers cytoplasmic contents to the lysosome for degradation. It is a "self-eating" process and plays a "house-cleaner" role in cells. The complex process consists of several sequential steps-induction, autophagosome formation, fusion of lysosome and autophagosome, degradation, efflux transportation of degradation products, and autophagic lysosome reformation. In this review, the cellular and molecular regulations of late stage of autophagy, including cellular events after fusion step, are summarized.

Th1/Th2 shift in gut of mouse model of postinfectious irritable bowel syndrome / 中华消化杂志

Objective To observe the expressions of Th1 cytokin [interleukin (IL)-12] and Th2 cytokin (IL-4) in gut of the mouse model of postinfcctious irritable bowel syndrome (PI-IBS). Methods Thirty mice were divided into control group (n=8) and model group (n=22,infected with Trichinella spiralis). The weight of the mouse was measured weekly after infection. Visceral sensitivity of colorectal distention in mouse was accessed by abdominal withdrawal reflex (AWR) at 0 and 8 weeks after infection. All mice were sacrificed at the 8th week, and tissues of jejunum, terminal ileum, proximal colon and distal colon were observed for inflammation with HE staining. The mRNA and protein expressions of IL-12 and IL-4 were examined by RT-PCR and Western blotting, respectively. Results Two weeks after infection, body weight was decreased in model group compared with control group ( -1.08%±1.08 % vs 3.09%±1.85%, P<0.05), but there was no significant difference at the 8th week between two groups (P>0.05). Severe inflammation was observed in the gut of mouse 2 weeks after infection, however it was recovered at the 8th week. The score of AWR was higher in model group at 30,45 and 60 mmHg in comparison with control group (P<0.05), whereas the perceptual threshold was lower in model group than in the control group (P<0.05). In comparison with control group, increased expressions of IL-12 mRNA and protein in ileocecum and proximal colon as well as decreased expressions of IL-4 mRNA and protein in all parts of gut were found in model group (P<0.05). Conclusion Th1/Th2 shift may involve in gut of PI-IBS mouse, which provides a new idea for treatment of PI-IBS.

Th17 cells influence intestinal muscle contraction during Trichinella spiralis infection / 华中科技大学学报（医学）（英德文版）

Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility. The aim of the study was to use this experimental model to elucidate if Th17 cells are involved in the development of gastrointestinal hypermotility. Colonic smooth muscle contractility was investigated in response to acetylcholine. The levels of IL-17, IL-23 and TGF-beta1 in colon were measured by Western blotting. Flow cytometric detection of intracellular IFN-gamma/IL-4/IL-17 cytokine production was used to analyze the proportions of CD4+ T cells subsets in colon. Our results showed that colonic muscle contractility was increased 2 weeks post infection (PI) and stayed high 12 weeks PI when no discernible inflammation was present in the gut. The proportion of Th17 cells and the expression of IL-17 were up-regulated in colon 2 weeks PI and returned to normal 8 weeks PI. The content of IL-17 was correlated with the colonic smooth muscle hypercontracility 2 weeks PI. Meanwhile, TGF-beta1 was increased 2 weeks PI, while IL-23 was normal. Our results suggest that Th17 cells affect the colonic muscle contractility in mice infected with Trichinella spiralis at intestine stage but not at muscle stage and the effect of Th17 cells on muscle contractility might be induced by TGF-beta1. Other cytokines might be involved in the hypercontracility of colonic smooth muscle at muscle stage.

The value of Rome Ⅲ criteria in diagnosis and differentiation of functional dyspepsia / 中华消化杂志

Objective To evaluate the sensitivity and specificity of Rome Ⅲ criteria in diagnosis of functional dyspepsia (FD) and assess its value in differentiate FD from other organic diseases in upper gastrointestinal tract. Methods Four thousand nine hundred and sixty-two patients, who underwent gastroscopy from July to August 2006 and March to April 2007, were consecutively enrolled and interviewed face to face with a standard questionnaire. The patients who were diagnosed as FD were according to Rome Ⅲ criteria, and those who were diagnosed as upper gastrointestinal diseases, such as chronic erosive gastritis (CEG), gastric ulcer (GU), duodenal ulcer (DU) and gastric carcinoma (GC), were done by gastroscopy and pathology. The differences of clinical characteristics among these diseases were analyzed. Results The FD patients accounted for 7.58% (376/4962) with female in predominant (P = 0.000). The patient with CEG, GU, DU or GC accounted for 29.99% (1488/4962), 1.89% (94/4962),4.25% (211/4962) or 4.57% (227/4962), respectively, all with male in predominant (P<0.05). Further analysis indicated that the age of onset between patients with FD and DU was no difference, but was younger than those with other three diseases (P<0.05). The incidence of early satiation and postprandial in FD patients were higher than those in other patients (P<0.05). The incidence of belching, nausea and vomiting showed no difference among these patients(P>0.05). According to Rome Ⅲ criteria, the symptoms of epigastric pain, early satiation, postprandial fullness and epigastric burning had higher sensitivity and specificity (except epigastric burning)in diagnosing FD (P<0.05), with highest Youden index in epigastric pain (0.42) and postprandial fullness (0.46). Conclusion Rome Ⅲ criteria has high specificity and sensitivity in diagnosing FD, and also has an important value in differentiate FD from other organic diseases.

Phenotypic analysis of Th cells in colonic mucosa and peripheral blood of patients with ulcerative colitis / 中华消化杂志

Objective To analyze the changes of proportion of Th1/Th2/Th17 cells in colonic mucosa and peripheral blood in pathogenesis of ulcerative colitis (UC) and its significance. Methods Twenty patients with UC were enrolled according to the criterion established in Jinan in 2007 and 16 patients were served as controls. The phenotypes of the colonic mucosa and peripheral blood were analysis by using flow cytometry. The variation of proportion of Th1/Th2/Th17 in colonic lamina propria mononuclear cells (cLPMCs) and peripheral blood mononuclear cells (PBMCs) were compared between two groups. Results The proportion of Th17 cell in cLPMCs was increased in UC group compared with controls [3.75% (6.93%)vs. 1.25 (3.70%), P<0.05], whereas it was 1.40%(2.15%) in UC group and 0.70%(0.33%) in controls in PBMCs with significant difference (P<0.05). The proportion of Th17 cell in cLPMCs was positively correlated with clinical parameters of the disease (r=0.34, P<0.05). No difference was found in proportion of Th1 or Th2 cells in cLPMCs or PBMCs between UC group and controls. Conclusions Among three helper T cells, Th17 cell in UC patients is predominant both in colonic mucosa and peripheral blood, which can be used as an effective target for treatment.