BACKGROUND:The chronic progression of viral hepatitis and the terminal stage of cirrhosis impose a long-term disease burden on patients. The assessment of liver damage can be facilitated through the measurement of liver biomarkers. OBJECTIVES:To conduct a comprehensive analysis of the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), liver biomarkers, and cirrhosis via Mendelian randomization (MR). MATERIAL AND METHODS:A bidirectional multi-sample MR approach was used to extract data from publicly available genome-wide association studies (GWAS) databases. Information on liver biomarkers and cirrhosis, along with data from 351,885 HBV samples containing 19,079,722 single nucleotide polymorphisms (SNPs) and 176,698 HCV samples comprising 12,454,320 SNPs, were aggregated. The TwoSampleMR 0.5.7 package in R language facilitated the bidirectional MR analysis, utilizing methods such as inverse-variance weighting, weighted median and MR-Egger to investigate the causal relationships between HBV, HCV, liver biomarkers, and cirrhosis. RESULTS:The MR analysis revealed potential causal relationships between cirrhosis and HBV infection, indicating an increased probability of HBV as cirrhosis escalates (odds ratio (OR) = 1.253; 95% confidence interval (95% CI): 1.037-1.514; p = 0.019). Additionally, a potential causal link was observed between HBV and the level of aspartate aminotransferase (AST), with an increase in HBV leading to a gradual decrease in AST levels (OR = 0.972; 95% CI: 0.958-0.986; p < 0.01). A similar causal relationship was identified between HCV infection and cirrhosis, where the probability of cirrhosis significantly increases with rising HCV levels (OR = 2.213; 95% CI: 1.752-2.796; p < 0.01). The results demonstrated no pleiotropy or heterogeneity within the analysis. CONCLUSIONS:This research highlights a causal relationship between HBV and AST levels, suggesting that monitoring AST levels can indicate the extent of liver damage caused by chronic HBV infection. Additionally, causal connections were established between HBV, HCV and cirrhosis, emphasizing that cirrhosis represents the terminal stage of chronic HBV and HCV infections. By managing the progression of the disease, the risk of cirrhosis can be reduced.

BackgroundThe suppression of the fibroblast growth factor 21/fibroblast growth factor receptor 1 (FGF21/FGFR1) signaling pathway is considered as a vital factor in the type 2 diabetes mellitus (T2DM) progression. Our previous study showed that gentiopicroside (GPS), the main active compound present in Gentiana macrophylla Pall., has the capacity to control disorders related to glucose and lipid metabolism in individuals with T2DM. Nevertheless, the specific mechanism remains unclear.PurposeIn light of the fact that the PharmMapper database suggests FGFR1 as the target of GPS, our investigation aims to determine if GPS can enhance glucose and lipid metabolism issues in T2DM by modulating the FGF21/FGFR1 signaling pathway.MethodsIn this study, we used palmitic acid (PA)-induced HepG2 cells and db/db mice to investigate the function and mechanism of GPS in the FGF21/FGFR1 signaling pathway. To examine the interaction between GPS and FGFR1, researchers performed Cellular Thermal Shift Assay (CETSA) and Surface Plasmon Resonance (SPR) analysis.ResultsThe results suggest that GPS activates the traditional metabolic pathways, including PI3K/AKT and AMPK, which are the subsequent stages of the FGF21/FGFR1 pathway. This activation leads to the enhancement of glucose and lipid metabolism issues in PA-treated HepG2 cells and db/db mice. Furthermore, the depletion of FGFR1 has been noticed to oppose the stimulation of PI3K/AKT and AMPK pathways by GPS in HepG2 cells subjected to PA. Notability, our research affirms that GPS binds directly to FGFR1, hindering the ubiquitinated degradation of FGFR1 by neural precursor cells expressing developmentally decreased protein 4 (NEDD4) and ultimately promoting FGF21 signal transduction.ConclusionThis study demonstrates that GPS targeting FGFR1 activates the PI3K/AKT and AMPK pathways, which is an important mechanism for its treatment of T2DM.

BACKGROUND:Hepatic fibrosis is a severe liver disease that has threatened human health for a long time. In order to undergo timely and adequate therapy, it is important for patients to obtain an accurate diagnosis of fibrosis. Laboratory inspection methods have been efficient in distinguishing between advanced hepatic fibrosis stages (F3, F4), but the identification of early stages of fibrosis has not been achieved. The development of proteomics may provide us with a new direction to identify the stages of fibrosis.METHODS:We established serum proteomic maps for patients with hepatic fibrosis at different stages and identified differential expression of proteins between fibrosis stages through ultra-high-performance liquid chromatography tandem mass spectrometry proteomic analysis.RESULTS:From the proteomic profiles of the serum of patients with different stages of liver fibrosis, a total of 1,338 proteins were identified. Among three early fibrosis stages (control, F1, and F2), 55 differential proteins were identified, but no proteins simultaneously exhibited differential expression between control, F1, and F2. Differential proteins were detected in the comparison between different fibrosis stages. Significant differences were found between advanced fibrosis stages (F2-vs.-F3 and F3-vs.-F4) through a series of statistical analysis, including hierarchical clustering, Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction network analysis. The differential proteins identified by GO annotation were associated with biological processes (mainly platelet degranulation and cell adhesion), molecular functions, and cellular components.CONCLUSIONS:All potential biomarkers identified between the stages of fibrosis could be key points in determining the fibrosis staging. The differences between early stages may provide a useful reference in addressing the challenge of early fibrosis staging.

目的 探讨miR-203对酒精性肝病(ALD)大鼠肝损伤的保护作用及其作用机制.方法 将60只SD大鼠随机分为ALD组(A组)、NC-miRNA/ALD组(B组)和miR-203/ALD组(C组).将慢病毒质粒经尾静脉注射感染大鼠,并采用酒精饮料喂养法建立ALD模型,采用Realtime PCR法检测大鼠肝组织miR-203水平,常规行病理学检查,评估大鼠肝组织损伤情况.使用市售试剂盒检测大鼠肝组织匀浆超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和丙二醛(MDA)水平,采用Western Blot法检测肝组织IL-1β3和NF-κB蛋白表达.结果 在建模8 w末,C组大鼠肝组织miR-203水平为(2.8±0.1),显著高于B组[(1.3±0.5),P＜0.05];C组动物血清AST、ALT和TBIL水平分别为(89.5±7.9) U/L、(38.5±10.1) U/L和(27.8±5.1) μmol/L,显著低于B组[(162.8±16.5)U/L、(69.6±7.5) U/L和(54.9±7.8) μmol/L,P＜0.05];C组肝组织匀浆SOD和CAT水平分别为(57.6±11.4) U/mg和(54.6±9.9) U/mg,显著高于B组[(41.6±7.6) U/mg和(45.7±6.0) U/mg,P＜0.05],而MDA水平为(2.8±0.1) nmol/g,显著低于B组[(5.0±0.2)nmol/g,P＜0.05];Western Blot检测结果表明,C组肝组织IL-1β蛋白和NF-κB表达分别为(0.7±0.2)和(0.3±0.1),显著低于B组[(1.2±0.3)和(1.0±0.2),P＜0.05].结论 miR-203过表达对ALD大鼠肝损伤起到了保护作用,其可能的机制是增强了抗氧化和抗炎作用.

We firstly reported a case of acute myelitis in a SARS-CoV-2-infected patient. A 66-year-old man with COVID-19 was admitted with acute flaccid paralysis of bilateral lower limbs and urinary and bowel incontinence. All serum microbiological studies were negative except for SARS-CoV-2 nucleic acid testing. Clinical findings could be ascribed to a post-infectious acute myelitis. He was receiving treatment with ganciclovir, lopinavir/ritonavir, moxifloxacin, dexamethasone, human immunoglobulin and mecobalamin. With a diagnosis of post-infectious acute myelitis and comprehensive treatment, paralysis of bilateral lower extremities ameliorated. After two times negative novel coronavirus RNA nasopharyngeal swabs tests, he was discharged and transferred to a designated hospital for isolation treatment and rehabilitation therapy.

Background At present, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, is spreading all over the world, with disastrous consequences for people of all countries. The traditional Chinese medicine prescription Dayuanyin (DYY), a classic prescription for the treatment of plague, has shown significant effects in the treatment of COVID-19. However, its specific mechanism of action has not yet been clarified. This study aims to explore the mechanism of action of DYY in the treatment of COVID-19 with the hope of providing a theoretical basis for its clinical application. Methods First, the TCMSP database was searched to screen the active ingredients and corresponding target genes of the DYY prescription and to further identify the core compounds in the active ingredient. Simultaneously, the Genecards database was searched to identify targets related to COVID-19. Then, the STRING database was applied to analyse protein-protein interaction, and Cytoscape software was used to draw a network diagram. The R language and DAVID database were used to analyse GO biological processes and KEGG pathway enrichment. Second, AutoDock Vina and other software were used for molecular docking of core targets and core compounds. Finally, before and after application of DYY, the core target gene IL6 of COVID-19 patients was detected by ELISA to validate the clinical effects. Results First, 174 compounds, 7053 target genes of DYY and 251 genes related to COVID-19 were selected, among which there were 45 target genes of DYY associated with treatment of COVID-19. This study demonstrated that the use of DYY in the treatment of COVID-19 involved a variety of biological processes, and DYY acted on key targets such as IL6, ILIB, and CCL2 through signaling pathways such as the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and cytokine-cytokine receptor interaction. DYY might play a vital role in treating COVID-19 by suppressing the inflammatory storm and regulating immune function. Second, the molecular docking results showed that there was a certain affinity between the core compounds (kaempferol, quercetin, 7-Methoxy-2-methyl isoflavone, naringenin, formononetin) and core target genes (IL6, IL1B, CCL2). Finally, clinical studies showed that the level of IL6 was elevated in COVID-19 patients, and DYY can reduce its levels. Conclusions DYY may treat COVID-19 through multiple targets, multiple channels, and multiple pathways and is worthy of clinical application and promotion.

Abstract Background Various types of pulmonary diseases are associated with iron deficiency. However, information on iron status in coronavirus disease 2019 (COVID-19) is scarce. Methods This study included 50 hospitalized patients with confirmed COVID-19. The role of serum iron in predicting severity and mortality of COVID-19 was evaluated. Results The most common symptoms of COVID-19 patients in this study were cough (82%), fever (64%), and chest distress (42%). Of the 50 patients, 45 (90%) patients had abnormally low serum iron levels (<7.8 μmol/L). The severity of COVID-19 was negatively correlated with serum iron levels before and after treatment and was positively correlated with C-reactive protein, serum amyloid A, D-dimer, lactate dehydrogenase, urea nitrogen, and myoglobin levels. Decreased serum iron level could predict the transition of COVID-19 from mild to severe and critical illness. Seven (53.8%) patients with a lower serum iron level after treatment in the critical group had died. There was a significant difference in posttreatment serum iron levels between COVID-19 survivors and nonsurvivors. Conclusions Serum iron deficiency was detected in the patients with COVID-19. The severity and mortality of the disease was closely correlated with serum iron levels. Low serum iron concentration was an independent risk factor for death in COVID-19 patients.

结合重型老年患者病案1则,介绍从湿温论治新型冠状病毒肺炎的临床体会.认为本病初期邪伏膜原,进展期湿邪壅肺,重症期邪入营血,恢复期余热渐退;在西医常规治疗的同时,中医辨证加用达原饮合三仁汤清热利湿、透达膜原,有助予提高临床疗效.

目的:探究微小RNR-133(miR-133)对肝癌细胞增殖、侵袭和迁移的影响及其作用机制.方法:采用实时定量PCR检测miR-133在肝癌组织或肝癌细胞中的表达.采用Lipofectamine 2000试剂转染miR-133模拟物和miR-133抑制物,随后采用CCK-8和Transwell实验分析人肝癌细胞系HepG2细胞的增殖、侵袭和迁移能力变化.通过PicTar软件预测miR-133的靶基因,并进一步通过双荧光素酶报告实验验证其结合能力.最后利用蛋白质印迹法检测蛋白表达变化.结果:miR-133在肝癌组织和肝癌细胞中的表达显著降低.miR-133能够抑制HepG2细胞的增殖、迁移及侵袭能力.此外,miR-133能够靶向调控表皮生长因子受体(EGFR)的表达,敲低EGFR防止了miR-133下调对肿瘤细胞增殖、侵袭及迁移能力的促进作用.结论:miR-133通过影响EGFR表达而抑制肝癌细胞的增殖、侵袭及迁移.

Objective:To discuss and analyze renal protecctive effect of Alprostadil on patients with end-stage liver diseases. Methods:80 patients were divided into 4 groups according to dose. The clinical situation of each group was observed, and the effeccts of these groups were compared. Results:After the end of treatment, the symptoms of the patients in each group had different degrees of improvement, and increased urine output and creatinine clearance occurred. The use of Alprostadil 80 μg/day, you can achieve the best therapeutic effect. Conclusions:The results show that the use of Alprostadil 80 μg/ day has the best therapeutic effect, and has a certain renal protective effects for the patients with end-stage liver diseases.