Systemic lupus erythematosus is associated with lower risk of hepatitis B virus infection: A multivariable Mendelian randomization study in East Asian population.

The relationship between systemic lupus erythematosus (SLE) and hepatitis B virus (HBV) infection is still unclear. We conducted a two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies for SLE and HBV infection in individuals of East Asian ancestry. The inverse-variance weighted (IVW) method, weighted median (WM) method, and MR-Egger method were used to estimate the causal effect of SLE on HBV infection. Additionally, we performed a multivariable MR analysis adjusting for the effects of body mass index and rheumatoid arthritis. This MR study included a total of 225 106 individuals of East Asian ancestry, comprising 5616 cases and 219 490 controls. The IVW method (OR: 0.79, p = 3.34E-08) and the WM method (OR: 0.79, p = 9.09E-06) revealed a causal relationship between genetically predicted SLE and a low risk of HBV infection. The multivariable MR analysis still suggested a low risk of HBV infection associated with SLE (OR: 0.83, p = 2.89E-06). Our MR analysis supports a causal relationship between SLE and a low risk of HBV infection in individuals of East Asian ancestry.

Causal associations between human gut microbiota and cholelithiasis: a mendelian randomization study.

Background: There was some evidence that gut microbiota was closely related to cholelithiasis, but the causal relationship between them remained unclear. In this study, we try to use Two-sample Mendelian randomization (MR) to clarify the potential causal relationship between gut microbiota and cholelithiasis. Methods: Summary Genome-Wide Association Studies (GWAS) statistical data for gut microbiota was obtained from MiBioGen, and the data of cholelithiasis was obtained from UK Biobank (UKB). Two-sample MR analyses were performed to assess causalities between gut microbiota and cholelithiasis mainly using the inverse-variance weighted (IVW) method. Sensitivity analyses were used to determine the robustness of the MR results. Reverse MR analyses were performed to examine the reverse causal association. Results: Our research results, based primarily on the IVW method, support the existence of a causal relationship between nine gut microbial taxa and cholelithiasis. We observed a positive association between Genus Butyrivibrio (p=0.032), Genus Lachnospiraceae_UCG_001 (p=0.015), Genus Ruminococcaceae_NK4A214_group (p=0.003), Genus Ruminococcaceae_UCG_011 (p=0.010) and cholelithiasis, while Order Rhodospirillales (p=0.031), Genus Actinomyces (p=0.010), Genus Phascolarctobacterium (p=0.036), Genus Rikenellaceae_RC9_gutgroup (p=0.023), Genus Ruminococcaceae_UCG_013 (p=0.022) may be associated with a reduced risk of cholelithiasis. We did not find a reverse causal relationship between cholelithiasis and 9 specific gut microbial taxa. Conclusions: This is the first mendelian randomization study to explore the causalities between specific gut microbiota taxa and cholelithiasis, which may provide new ideas and a theoretical basis for the prevention and treatment of cholelithiasis in the future.

Systemic lupus erythematosus is causally associated with hypothyroidism, but not hyperthyroidism: A Mendelian randomization study.

Background: The relationship between systemic lupus erythematosus (SLE) and thyroid diseases is still controversial. Due to confounders and reverse causation, previous studies were not convincing. We aimed to investigate the relationship between SLE and hyperthyroidism or hypothyroidism by Mendelian randomization (MR) analysis. Methods: We performed a two-step analysis using bidirectional two-sample univariable and multivariable MR (MVMR) to explore the causality of SLE and hyperthyroidism or hypothyroidism in three genome-wide association studies (GWAS) datasets, including 402,195 samples and 39,831,813 single-nucleotide polymorphisms (SNPs). In the first step analysis, with SLE as exposure and thyroid diseases as outcomes, 38 and 37 independent SNPs strongly (P < 5*10-8) associated with SLE on hyperthyroidism or SLE on hypothyroidism were extracted as valid instrumental variables (IVs). In the second step analysis, with thyroid diseases as exposures and SLE as outcome, 5 and 37 independent SNPs strongly associated with hyperthyroidism on SLE or hypothyroidism on SLE were extracted as valid IVs. In addition, MVMR analysis was performed in the second step analysis to eliminate the interference of SNPs that were strongly associated with both hyperthyroidism and hypothyroidism. 2 and 35 valid IVs for hyperthyroidism on SLE and hypothyroidism on SLE were obtained in MVMR analysis. MR results of two steps analysis were estimated respectively by multiplicative random effects-inverse variance weighted (MRE-IVW), simple mode (SM), weighted median (WME) and MR-Egger regression methods. Sensitivity analysis and visualization of MR results were performed by heterogeneity test, pleiotropy test, leave-one-out test, scatter plots, forest plots and funnel plots. Results: The MRE-IVW method in the first step of MR analysis revealed that SLE was causally associated with hypothyroidism (OR = 1.049, 95% CI = 1.020-1.079, P < 0.001), but not causally associated with hyperthyroidism (OR = 1.045, 95% CI = 0.987-1.107, P = 0.130). In the inverse MR analysis, the MRE-IVW method revealed that both hyperthyroidism (OR = 1.920, 95% CI = 1.310-2.814, P < 0.001) and hypothyroidism (OR = 1.630, 95% CI = 1.125-2.362, P = 0.010) were causally associated with SLE. Results from other MR methods were consistent with MRE-IVW. However, when MVMR analysis was performed, there was no longer a causal relationship of hyperthyroidism on SLE (OR = 1.395, 95% CI = 0.984-1.978, P = 0.061), nor was there a causal relationship of hypothyroidism on SLE (OR = 1.290, 95% CI = 0.823-2.022, P = 0.266). The stability and reliability of the results were confirmed by sensitivity analysis and visualization. Conclusions: Our univariable and multivariable MR analysis revealed that systemic lupus erythematosus was causally associated with hypothyroidism, but did not provided evidence to support a causal relationship of hypothyroidism on SLE or between SLE and hyperthyroidism.

Structural and Temporal Dynamics of Mesenchymal Stem Cells in Liver Diseases From 2001 to 2021: A Bibliometric Analysis.

Background: Mesenchymal stem cells (MSCs) have important research value and broad application prospects in liver diseases. This study aims to comprehensively review the cooperation and influence of countries, institutions, authors, and journals in the field of MSCs in liver diseases from the perspective of bibliometrics, evaluate the clustering evolution of knowledge structure, and discover hot trends and emerging topics. Methods: The articles and reviews related to MSCs in liver diseases were retrieved from the Web of Science Core Collection using Topic Search. A bibliometric study was performed using CiteSpace and VOSviewer. Results: A total of 3404 articles and reviews were included over the period 2001-2021. The number of articles regarding MSCs in liver diseases showed an increasing trend. These publications mainly come from 3251 institutions in 113 countries led by China and the USA. Li L published the most papers among the publications, while Pittenger MF had the most co-citations. Analysis of the most productive journals shows that most are specialized in medical research, experimental medicine and cell biology, and cell & tissue engineering. The macroscopical sketch and micro-representation of the whole knowledge field are realized through co-citation analysis. Liver scaffold, MSC therapy, extracellular vesicle, and others are current and developing areas of the study. The keywords "machine perfusion", "liver transplantation", and "microRNAs" also may be the focus of new trends and future research. Conclusions: In this study, bibliometrics and visual methods were used to review the research of MSCs in liver diseases comprehensively. This paper will help scholars better understand the dynamic evolution of the application of MSCs in liver diseases and point out the direction for future research.

[An analysis of factors for quality-of-life in patients with chronic cough].

OBJECTIVE: To constitute a correlation with the subjective indicators by investigation of the causes and clinical features in patients with chronic cough. METHODS: Totally 100 patients with chronic cough were recruited followed a diagnostic program. Airway responsiveness [by methacholine challenge test (MCT)], Leicester cough questionnaire (LCQ), visual analogue scale (VAS), cough score, age, gender and disease duration were all recorded for analysis. RESULTS: The top five causes of chronic cough in these patients were variant asthma, post infectious cough, atopic cough, eosinophilic bronchitis and upper airway cough syndrome. LCQ total score was negatively correlated with age and the VAS score (r = -0.239 and -0.470 respectively, all P < 0.05), while no difference was found among patients with different causes of disease or gender (F = 1.233, t = 1.918, all P > 0.05) and no correlation was found with BMI (r = -0.029, P > 0.05). The physiological and psychological field score in female patients significantly reduced (t = 2.174, 1.990, P < 0.05), and LCQ total score of MCT positive patients obviously reduced than negative ones (t = -2.22, P < 0.05). After the treatment of two weeks, LCQ three component field and total score could be improved significantly (all P < 0.01). CONCLUSIONS: Gender and age may have some impact on the quality of life in patients with chronic cough. LCQ, VAS and cough score should be used to assess cough severity and evaluate therapeutic effect in patients with chronic cough.

[The levels of nerve growth factor and IL-4 in induced sputum and characteristics of airway inflammation in cough variant asthma].

OBJECTIVE: To observe sputum cytology counts, the levels of nerve growth factor (NGF) and IL-4 in cough variant asthma (CVA) patients and the change of their levels after using glucocorticoids combined with ß(2)-adrenergic agonists one month, and to investigate CVA's characteristics of airway inflammation. METHODS: Totally 36 patients with untreated CVA were selected, as well as 23 healthy controls. Coughed up sputum cells were obtained and HE strained for differential cell counting in each enrolled patient. In induced sputum's supernatant, the levels of NGF and IL-4 were determined by ELISA. RESULTS: Before treatment, CVA patients had a median eosinophils (EOS) percentage of 8%, which was significantly higher than that after treatment (2%, P < 0.05) and in healthy control group (1%, P < 0.001). The levels of NGF and IL-4 in induced sputum of CVA group were (9.50 ± 1.69) ng/L and (257.37 ± 53.57) ng/L. After treatment, they were (8.78 ± 1.02) ng/L and (228.60 ± 52.93) ng/L in CVA group, (6.98 ± 0.69) ng/L and (166.44 ± 24.75) ng/L in healthy control group. The levels of NGF and IL-4 before and after treatment in the CVA group, as compared with the healthy control group, had statistically significant differences (all P < 0.001). In CVA group before and after treatment, the level of NGF and IL-4 paired difference was significant (P < 0.001). The percentage of induced sputum EOS correlated with sputum supernatant concentrations of NGF and IL-4 (P < 0.01). In induced sputum supernatant, the concentrations of NGF and IL-4 were significant correlated (P < 0.01). CONCLUSIONS: Glucocorticoid joint long-term ß(2) agonist inhaled treatment significantly reduced NGF, IL-4 and EOS levels and reduced eosinophilic inflammation, which are closely related with the nerve-immune mechanism, NGF as well as IL-4 participated the inflammation. Induced sputum examination is non-invasive, economical, simple, easily accepted by patients, and repeatable, widely used in clinical.