[An analysis on clinical characteristics and prognosis-related risk factors in patients with drug-induced liver injury].

Objective: To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely. Methods: A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI. Results: Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T(0.5ALP) and T(0.5ALT)) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC) = 0.787, 95%CI: 0.697~0.878, P < 0.001], with cutoff values of 12.5d and 9.5d, respectively. Conclusion: Traditional Chinese medicine is the main contributing cause of DILI. The occurrence risk of severe DILI is related to preexisting gallbladder disease, initial total bilirubin, prothrombin time, and antinuclear antibodies. T(0.5ALP) and T(0.5ALT) can be used as indicators to predict chronic DILI.

[Regulatory effects of microRNAs on hepatic stellate cell activation and liver fibrogenesis].

Hepatic fibrogenesis (HF) is the common consequence of various chronic liver diseases (CLD) induced by a variety of pathogenic factors. The mechanism of HF involves the interactions within different types of liver cells, cytokines, chemokines, cell mediators and multiple signaling pathways in a way of networks. As a result, excessive production and deposition of extracellular matrix (ECM) mainly composed of type I and type III fibril forming collagen destroys the original morphology, structure and function of the liver. The activation of hepatic stellate cells (HSCs), the major scar forming cells in liver, plays a crucial role in hepatic fibrogenesis. MicroRNAs are a group of short, single stranded, non-coding RNAs that can inhibit mRNA expression at the transcriptional and post transcriptional levels. They can be loaded and transferred as cargos by exosomes, to regulate the function of nearby and distant receptive cells. The expressions of many microRNAs such as miR-21, miR-29, miR-708, miR-101, miR-455, miR-146, miR-193 change significantly in activated HSCs, which regulate the activation, fibrogenic function, proliferation, apoptosis and autophagy of HSCs via affecting target genes expression and signaling pathway molecules. They are important substances and regulatory mechanism that mediate the initiation and progression of HF.

[Effect of occupational stress on depression in gas field workers].

Objective: To explore the occurrence level of depressive symptoms and it's influencing factors among gas field workers. Methods: In October 2018, a cross-sectional study was conducted in 1726 gas field workers from a gas field by using cluster sampling method. Questionaire was used to evaluate the individual factors, depressive symptoms, occupational stress factors and stress regulatory factors. The correlation between depressive symptoms and occupational stress was analyzed. Multivariate logistic regression was used to analyze the influencing factors of depressive symptoms. Results: The depressive symptoms score of gas field workers was 12.00 (7.00, 19.00) point. Correlation analysis revealed that depressive symptoms score was positively related to sleep disorders (r=0.598) , effort (r=0.186) , daily tension (r=0.478) , negative affectivity (r=0.565) , social support (r=0.446) and monotony of work (r=0.484) (P<0.01) . And it was negatively related to reward (r=-0.386) , work stability (r=-0.294) , promotion opportunities (r=-0.258) , positive affectivity (r= -0.310) , self-efficacy (r=-0.312) , contral strategy (r=-0.268) , support strategy (r=-0.209) and job satisfaction (r=-0.398) (P<0.01) . Multivariate logistic regression analysis revealed that sleep disorder, high negative affectivity, low support from colleagues, low support from family, high monotony of work and high daily tension were the risk factors for depressive symptoms of gas field worker (OR=3.423, 95%CI: 2.644-4.397; OR=2.847, 95%CI: 2.200-3.683; OR=1.646, 95%CI: 1.215-2.116; OR=1.496, 95%CI: 1.164-1.923; OR=1.578, 95%CI: 1.227-2.303; OR=1.903, 95%CI: 1.480-2.440; P<0.01) . High work stability, high self-efficacy and high job satisfaction were protective factors for depressive symptoms of gas field workers (OR=0.752, 95%CI: 0.591-0.958; OR=0.590, 95%CI: 0.465-0.749; OR=0.718, 95%CI: 0.516-0.999; P<0.05) . Conclusion: Occupational stress factors have a great influence on the depressive symptoms of gas field workers. Increased work stability, self-efficacy and job satisfaction could reduce the risk of depressive symptoms.

[Correlation between social support and occupational stress among gas production workers in the field].

Objective: To investigate the level of social support and its correlation with occupational stress among gas production workers in the field. Methods: In October 2018, the cluster sampling method was used to perform a cross-sectional survey for 1726 gas production workers in the field, and related data of these workers were collected, including age, education level, marital status, level of social support, and related factors for occupational stress. A Spearman's rank correlation analysis was used to investigate the correlation between social support and occupational stress, and the levels of occupational stress-related factors were compared between the groups with different social support scores. Results: The gas production workers in the field had a median (25th percentile, 75th percentile) social support score of 24.00 (19.00, 28.00) , and there was a significant difference in social support score between the workers with different posts or work shifts (P<0.01) . Social support score was positively correlated with effort, daily stress, negative emotion, and job routinization (P<0.05) and was negatively correlated with job satisfaction, reward, working stability, and promotion opportunity (P<0.05) . The group with a high social support score had significantly higher scores of effort, job routinization, sleep disorders, and daily stress than the other two groups (P<0.01) , and the group with a low social support score had significantly higher scores of reward, self-efficacy, positive affection, and job satisfaction than the other two groups (P<0.01) . Conclusion: High-level social support plays an important role in alleviating occupational stress and protecting mental health among gas production workers in the field.

Innovative development ideas of web-based medical teaching during the COVID-19 epidemic.

OBJECTIVE: In response to the sudden COVID-19 epidemic outbreak, China's Ministry of Education proposed "continuing teaching and learning regardless of suspending classes" to provide "available courses and teachers" for students. Web-based teaching has become the main teaching method of medical colleges and universities during the COVID-19 epidemic period. Before the outbreak, the concept and technology of web-based teaching had been partially implemented. The epidemic situation has promoted the implementation of large-scale web-based teaching and the multidimensional development of education in China. Furthermore, there are higher requirements for information teaching. Teachers and students cannot adapt to the web-based teaching mode. The lack of interaction is a problem in the web-based teaching. To adapt to the rapid development of information technology, medical colleges and universities must consider the COVID-19 epidemic as an opportunity to quickly update educational concepts, train teachers' Internet thinking, innovate the web-based teaching mode, and make full use of the network platform to provide better teaching and services. Moreover, medical colleges and universities should eliminate the weaknesses of web-based teaching and improve the quality and connotation of teaching.

[Sleep quality and occupational stress relationship analysis of field gas recovery workers].

Objective: To explore the relationship between sleep quality and occupational stress in field gas recovery workers. Methods: In October 2018, cluster sampling method was adopted to conduct cross-sectional survey on 1726 field workers in a gas production oilfield. The individual characteristics, occupational stress factors, stress regulation factors, stress response and sleep quality, social support and coping strategies were evaluated by occupational stress measurement tools and job content questionnaire. Mann Whitney U test and Kruskal Wallis H test were used to compare sleep quality scores between the groups. Spearman rank correlation analysis was used to analyze the correlation between sleep quality and occupational stress, and logistic regression analysis was used to analyze multiple factors. Results: There were significant differences in sleep quality scores among different positions, gender, marital status, age, length of service, smoking and drinking (P<0.05) . There were no significant differences in sleep quality scores between different education levels and work shift groups (P>0.05) . Spearman rank correlation analysis showed that sleep quality score was negatively correlated with job satisfaction, reward, job stability, promotion opportunity, positive emotion, respect, self-esteem, control strategy, support strategy and self-efficacy score (r(s)=-0.361, -0.311, -0.238, -0.261, -0.248, -0.212, -0.139, -0.188, -0.152, -0.226, P<0.01) , and was positively correlated with social support, giving, daily tension, negative emotion, work monotony and depression symptom (r(s)=0.312, 0.279, 0.547, 0.493, 0.429, 0.599, P<0.01) . Compared with the high sleep quality score group, the middle and low sleep quality score groups had lower giving, work monotony, daily tension, depressive symptoms, negative emotions and social support (P<0.01) , while the scores of respect, reward, job satisfaction, positive emotion, self-efficacy, job stability, promotion opportunity, control strategy and support strategy were higher (P<0.01) . Multiple depressive symptoms, high daily tension, high negative emotion and high work monotony were the risk factors for sleep disorders (OR=3.417, 2.659, 2.913, 1.543) . Conclusion: Depressive symptoms, daily tension and negative emotion have great influence on sleep quality of field gas recovery workers.

[Research hotspots and progress of hepatic fibrosis - 2019 viewpoints].

The application of modern bioinformatics, 'omics' and molecular biology to research of fibrotic liver diseases holds promise to accelerate the development of new therapeutic targets and therapies for hepatic fibrosis. Specifically, progress is anticipated in delineating pathways of fibrosis reversal and functional compensation, and defining key determinants and presenting factors associated with fibrosis progression and reversion. These efforts will also lead to develop accurate biomarkers and methods for early noninvasive diagnosis, and to accelerate the testing of anti-fibrotic drugs.

[Research progress of extracellular vesicles in hepatic fibrosis].

Liver fibrosis is a pathophysiological process characterized by abnormal accumulation of connective tissues in the liver caused by chronic liver injuries, in which the activation and migration of hepatic stellate cells (HSCs) play a central role. Extracellular vesicles (EVs) are a class of nanoscale, bilayer lipid enveloped vesicles secreted by almost all cells. EVs are of great interest in liver pathology because they have been found to mediate the communication between cells and regulate cellular microenvironment via horizontal transfer of their cargoes. EVs carry bioactive cargoes including proteins, lipids and RNA molecules, and are involved in the activation of HSCs during liver fibrogenesis.

[The application of non-selective ß-blockers, angiotensin receptor antagonists and statins in liver cirrhotic patients].

Portal hypertension is the major cause of complications in decompensated liver cirrhosis. Research results showed that non-selective ß-blockers, angiotensin receptor antagonists, and statins can improve portal hypertension by reducing portal vein blood flow and intrahepatic resistance, and have certain prevention and treatment effect on hemodynamic disorders and portal hypertensive complications in chronic liver diseases. Herein, we review the mechanism of action, clinical effects and limitations of these three types of drugs on portal hypertension of cirrhosis.

[Epigenetics and liver fibrogenesis].

Epigenetic modification refers to a variety of regulating processes that may induce the changes in gene expression without altering DNA sequence. Epigenetic mechanisms including DNA methylation, histone modification, and regulatory non-coding RNAs are involved in hepatic stellate cell activation and liver fibrogenesis. A deep understanding of epigenetic mechanisms in liver fibrosis helps to identify new markers and therapies for liver fibrosis.

[Clinical features and significance of cirrhosis-associated immune dysfunction].

Cirrhosis-associated immune dysfunction (CAID) refers to immunodeficiency and systemic inflammation in cirrhotic patients and is the characteristic pathophysiological change of liver cirrhosis of various causes. The phenotype of CAID changes dynamically with the progression of liver cirrhosis. In patients with stable cirrhotic ascites, CAID is manifested as "pro-inflammatory" state, and in patients with severe decompensated liver cirrhosis complicated by extrahepatic organ failure, it is manifested as "immunodeficiency". CAID affects the clinical manifestations and prognosis of liver cirrhosis, aggravates the condition of cirrhotic patients, and increases the risk of infection. This article briefly introduces the mechanism, features, and clinical significance of CAID.

Overexpression of EsMcsu1 from the halophytic plant Eutrema salsugineum promotes abscisic acid biosynthesis and increases drought resistance in alfalfa (Medicago sativa L.).

The stress phytohormone abscisic acid (ABA) plays pivotal roles in plants' adaptive responses to adverse environments. Molybdenum cofactor sulfurases influence aldehyde oxidase activity and ABA biosynthesis. In this study, we isolated a novel EsMcsu1 gene encoding a molybdenum cofactor sulfurase from Eutrema salsugineum. EsMcus1 transcriptional patterns varied between organs, and its expression was significantly upregulated by abiotic stress or ABA treatment. Alfalfa plants that overexpressed EsMcsu1 had a higher ABA content than wild-type (WT) plants under drought stress conditions. Furthermore, levels of reactive oxygen species (ROS), ion leakage, and malondialdehyde were lower in the transgenic plants than in the WT plants after drought treatment, suggesting that the transgenic plants experienced less ROS-mediated damage. However, the expression of several stress-responsive genes, antioxidant enzyme activity, and osmolyte (proline and total soluble sugar) levels in the transgenic plants were higher than those in the WT plants after drought treatment. Therefore, EsMcsu1 overexpression improved drought tolerance in alfalfa plants by activating a series of ABA-mediated stress responses.

IL28B rs12979860 polymorphism does not influence outcomes of hepatitis B virus infection.

rs12979860 in interleukin 28B (IL28B) gene is associated with response to interferon-α therapy and natural viral clearance in hepatitis C. The role of this polymorphism is less known in hepatitis B virus (HBV) infection. We evaluated whether rs12979860 was associated with outcomes of HBV infection. There were 651 individuals with persistent infection (387 with liver cirrhosis, 264 without cirrhosis) and 226 healthy individuals who recovered from HBV infection. The genotypic distributions were compared between different phenotypes pertaining to disease progression and HBV markers. The polymorphism had no association with clearance of hepatitis B surface antigen and hepatitis B e antigen, HBV-DNA level, apparent hepatitis onset and liver cirrhosis (P > 0.05). These results suggest that rs12979860 does not have such a strong effect in hepatitis B compared to hepatitis C.

Cotransplant of neural stem cells and NT-3 gene modified Schwann cells promote the recovery of transected spinal cord injury.

STUDY DESIGN: An animal model of transected spinal cord injury (SCI) was used to test the hypothesis that cografted neural stem cells (NSCs) and NT-3-SCs promote morphologic and functional recoveries of injured spinal cord. OBJECTIVE: To explore whether cotransplant of NSCs and NT-3-SCs could promote the injured spinal cord repair. SETTING: Zhongshan Medical College, Sun Yat-sen University, PR China. METHODS: Female Sprague-Dawley (SD) rats weighing on 200-220 g were used to prepare SCI models. The spinal cord was transected between T(9) and T(10), then NSCs, SCs+NSCs, LacZ-SCs+NSCs, or NT-3-SCs+NSCs were grafted into the transected site. RESULTS: (1) Part of NSCs could differentiate to neuron-like cells in the transected site and the percentage of differentiation was NT-3-SCs+NSCs group>SCs+NSCs group>NSCs group. (2) In the grafted groups, there were 5-HT, CGRP, and SP positive nerve fibres within the transected site. Some fluorogold (FG)-labeled cells were found in the spinal cord rostral to the transected site, the red nuclei and the inner pyramidal layer of sensorimotor cortex. (3) The cells grafted could enhance the injured neurons survival in inner pyramidal layer of sensorimotor cortex, red nuclei of midbrain, and Clark's nuclei of spinal cord's L1 segment, could decrease the latency and increase the amplitude of cortical somatosensory evoked potential (CSEP) and cortical motor evoked potential (CMEP), and could promote partly structural and functional recovery of the SCI rats. CONCLUSION: These results demonstrate that cografted NT-3-SCs and NSCs is a potential therapy for SCI. SPONSORSHIP: This research was supported by Chinese National Key Project for Basic Research (G1999054009), Chinese National Natural Science Foundation (30270700) and Social Developmental Foundation of Guangdong Province (2003C33808) to YS Zeng; Natural Science Foundation of Guangdong Province (04300468) and Medical Science Research Grant of Guangdong Province (A2004081) to JS Guo.

Over-expression of inducible heat shock protein 70 in the gastric mucosa of partially sleep-deprived rats.

BACKGROUND: Previous findings have demonstrated increased expression of inducible heat shock protein 70 (iHSP70) in the gastric mucosa of rats exposed to partial sleep deprived (PSD). The purpose of this study was to investigate the functional role of iHSP70 and its relationship with acid secretion in the stomachs of PSD animals. METHODS: A slowly rotating drum was used to induce PSD in male Sprague-Dawley rats with or without omeprazole treatment. Gastric mucosal samples were harvested for iHSP70 mRNA and protein analysis with RT-PCR and Western blotting, respectively. Enzyme immunoassay was used to determine plasma gastrin level and gastric acidity was measured by titration. The modulating effect of PSD on 0.6 M hydrochloric acid (HCl)-induced gastric damage was also evaluated. RESULTS: PSD increased plasma gastrin, gastric acidity and expression of iHSP70, while significantly reducing HCl-induced gastric damage. Omeprazole administration decreased gastric acidity and reversed iHSP70 over-expression in PSD rats. CONCLUSIONS: PSD increases gastric acidity which enhances expression of mucosal iHSP70. Over-expression of iHSP70 may be a protective homeostatic response of the stomach to stress induced by PSD and acid secretion.

Expression and immunolocalization of heat shock proteins in the healing of gastric ulcers in rats.

BACKGROUND: Heat shock proteins are induced when cells are subjected to noxious stimuli. They afford cytoprotection and increase the resistance of the tissue to damage. However, their roles in the healing of gastric ulcers have not been well established. In this study, the expression and immunolocalization of three heat shock proteins (HSPs); namely inducible HSP70 (iHSP70), HSP47, and HSP32 during ulcer healing were investigated in rats with gastric ulcer. METHODS: Gastric ulcers (kissing ulcers) were induced by luminal application of acetic acid solution. Gastric tissue samples were obtained from the ulcer base, ulcer margin, and non-ulcerated area around the ulcer margin at different time intervals after ulcer induction. The protein levels and distributions of HSPs were analyzed with Western blotting and immunohistochemical methods, respectively. RESULTS: It was found that all HSPs were expressed in normal, non-ulcerated, and gastric ulcer tissues. HSP32 was elevated during inflammation (1-8 days after ulcer induction), while HSP47 expression was exacerbated at the ulcer base and margin during ulcer healing (3-12 days). Decreased expression of iHSP70 was observed at the ulcer base immediately after ulcer induction, but returned to normal level by the end of the healing stage (8-12 days). Inducible HSP70 was found distributed in the gastric glands and injured tissues in the inflamed areas. Wide distribution of HSP47 was detected in granulation tissues and collagen producing cells, while HSP32 was localized in the gastric glands and inflammatory cells. CONCLUSIONS: The findings indicate that iHSP70, HSP47, and HSP32 play different roles during ulcer healing. HSP32 seems to act as an inflammatory defensive factor, and HSP47 as a collagen-specific molecular chaperon contributing significantly to gastric ulcer healing. However, the role of iHSP70 in the ulcer healing process is still undefined.

Maternal zinc deficiency impairs brain nestin expression in prenatal and postnatal mice.

Effects of maternal dietary zinc deficiency on prenatal and postnatal brain development were investigated in ICR strain mice. From d 1 of pregnancy (E0) until postnatal d 20 (P20), maternal mice were fed experimental diets that contained 1 mg Zn/kg/day (severe zinc deficient, SZD), 5 mg Zn/kg/day (marginal zinc deficient, MZD), 30 mg Zn/kg/day (zinc adequately supplied, ZA) or 100 mg Zn/kg/day (zinc supplemented, ZS and pair-fed, PF). Brains of offspring from these dietary groups were examined at various developmental stages for expression of nestin, an intermediate filament protein found in neural stem cells and young neurons. Immunocytochemistry showed nestin expression in neural tube 10.5 d post citrus (dpc) as well as in the cerebral cortex and neural tube from 10.5 dpc to postnatal d 10 (P10). Nestin immunoreactivities in both brain and neural tube of those zinc-supplemented control groups (ZA, ZS, PF) were stronger than those in zinc-deficient groups (SZD and MZD). Western blot analysis confirmed that nestin levels in pooled brain extracts from each of the zinc-supplemented groups (ZA, ZS, PF) were much higher than those from the zinc-deficient groups (SZD and MZD) from 10.5 dpc to P10. Immunostaining and Western blots showed no detectable nestin in any of the experimental and control group brains after P20. These observations of an association between maternal zinc deficiency and decreased nestin protein levels in brains of offspring suggest that zinc deficiency suppresses development of neural stem cells, an effect which may lead to neuroanatomical and behavioral abnormalities in adults.

[Effect of extract from overground part of Tripterygium wilfordii Hook. f. on Masugi nephritis in rabbits].

OBJECTIVE: To observe the effect of extract from overground part of Trpterygium wilfordii on Masugi nephritis in rabbits. METHOD: Masugi nephritis was made by giving i.v. the rabbit an injection of sheep antirabbit serum. RESULT: The extract could effectively inhibit the increase of uric protein, serum BUN, creatinine and glomerulus cells in rabbits. CONCLUSION: The extract from overground part of Tripterygium wilfordii has better curative effect on Masugi nephritis in rabbits.