No causal association between pneumoconiosis and three inflammatory immune diseases: a Mendelian randomization study.

Objectives: To investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout. Methods: The random-effects inverse variance weighted (IVW) approach was utilized to explore the causal effects of the instrumental variables (IVs). Sensitivity analyses using the MR-Egger and weighted median (WM) methods were did to investigate horizontal pleiotropy. A leave-one-out analysis was used to avoid the bias resulting from single-nucleotide polymorphisms (SNPs). Results: There was no causal association between pneumoconiosis and SLE, RA or gout in the European population [OR = 1.01, 95% CI: 0.94-1.10, p = 0.74; OR = 1.00, 95% CI: 0.999-1.000, p = 0.50; OR = 1.00, 95% CI: 1.000-1.001, p = 0.55]. Causal relationships were also not found in pneumoconiosis due to asbestos and other mineral fibers and SLE, RA and gout [OR = 1.01, 95% CI: 0.96-1.07, p = 0.66; OR = 1.00, 95% CI: 1.00-1.00, p = 0.68; OR = 1.00, 95% CI: 1.00-1.00, p = 0.20]. Conclusion: Our study suggests that pneumoconiosis may have no causal relationship with the three inflammatory immune diseases.

Perturbations in gut and respiratory microbiota in COVID-19 and influenza patients: a systematic review and meta-analysis.

Objectives: Coronavirus disease-19 (COVID-19)/influenza poses unprecedented challenges to the global economy and healthcare services. Numerous studies have described alterations in the microbiome of COVID-19/influenza patients, but further investigation is needed to understand the relationship between the microbiome and these diseases. Herein, through systematic comparison between COVID-19 patients, long COVID-19 patients, influenza patients, no COVID-19/influenza controls and no COVID-19/influenza patients, we conducted a comprehensive review to describe the microbial change of respiratory tract/digestive tract in COVID-19/influenza patients. Methods: We systematically reviewed relevant literature by searching the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2023. We conducted a comprehensive review to explore microbial alterations in patients with COVID-19/influenza. In addition, the data on α-diversity were summarized and analyzed by meta-analysis. Results: A total of 134 studies comparing COVID-19 patients with controls and 18 studies comparing influenza patients with controls were included. The Shannon indices of the gut and respiratory tract microbiome were slightly decreased in COVID-19/influenza patients compared to no COVID-19/influenza controls. Meanwhile, COVID-19 patients with more severe symptoms also exhibited a lower Shannon index versus COVID-19 patients with milder symptoms. The intestinal microbiome of COVID-19 patients was characterized by elevated opportunistic pathogens along with reduced short-chain fatty acid (SCFAs)-producing microbiota. Moreover, Enterobacteriaceae (including Escherichia and Enterococcus) and Lactococcus, were enriched in the gut and respiratory tract of COVID-19 patients. Conversely, Haemophilus and Neisseria showed reduced abundance in the respiratory tract of both COVID-19 and influenza patients. Conclusion: In this systematic review, we identified the microbiome in COVID-19/influenza patients in comparison with controls. The microbial changes in influenza and COVID-19 are partly similar.

Endocrine-disrupting chemicals and autoimmune diseases.

Endocrine-disrupting chemicals (EDCs) widely exist in people's production and life which have great potential to damage human and animal health. Over the past few decades, growing attention has been paid to the impact of EDCs on human health, as well as immune system. So far, researchers have proved that EDCs (such as bisphenol A (BPA), phthalate, tetrachlorodibenzodioxin (TCDD), etc.) affect human immune function and promotes the occurrence and development of autoimmune diseases (ADs). Therefore, in order to better understand how EDCs affect ADs, we summarized the current knowledge about the impact of EDCs on ADs, and elaborated the potential mechanism of the impact of EDCs on ADs in this review.

Essential Trace Element Status in Systemic Lupus Erythematosus: a Meta-analysis Based on Case-Control Studies.

The homeostasis of trace elements is essential to regulate different aspects of the immune system and might play important roles in systemic lupus erythematosus (SLE). However, epidemiological evidences that compared the level of essential trace elements in SLE patients and healthy controls (HCs) did not reach a consensus. This was the first meta-analysis to comprehensively assess the level of zinc (Zn), copper (Cu), iron (Fe), and selenium (Se) in SLE and HCs. PubMed, Embase, and Web of Science were systematically searched until April 2022 to find relevant literatures. The PRISMA statement 2020 was followed to make sure the quality of reporting a meta-analysis. The outcomes were assessed by pooled standardized mean difference (SMD) and 95% confidence intervals (CIs). Finally, eleven articles with 1262 subjects were included in the meta-analysis. Significantly lower levels of Zn (SMD = -0.709; 95% CI: -1.173, -0.245; P = 0.003) and Fe (SMD = -1.783; 95% CI: -2.756, -0.809; P = 0.000) were found in SLE compared with HCs. Higher levels of Cu (SMD = 0.808; 95% CI: 0.234, 1.382; P = 0.006) were found in SLE patients. In addition, compared with HCs, Fe and Zn were lower in SLE patients in Asia and Cu was higher in SLE patients in Europe. However, no significant difference was observed in the level of Se (SMD = -0.251; 95% CI: -1.087, 0.586; P = 0.557). Above all, SLE patients exhibited lower Zn and Fe and increased Cu concentrations compared with HCs. Further studies are warranted to investigate the mechanism of Zn, Cu, and Fe in SLE patients.

Intestinal fungi and systemic autoimmune diseases.

Nearly 20 years of studies have shown that fungi and the human immune system (non-specific immunity and specific immunity) and bacterial--fungal interactions maintain a balance that can't lead to diseases. Fungi--microorganism that lives in human intestine--may play an important role in human health and disease. Population studies and animal models in some diseases have found the changes in the diversity and composition of fungi. The dysregulation of the fungi can disrupt the normal "running" of the immune system and bacteria, which triggers the development of inflammatory diseases. The latest studies of fungi in inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and type 1 diabetes mellitus were summarized. This review considers how the healthy host protect against the potential harm of intestinal fungi through the immune system and how fungal dysregulation alters host immunity.

The effect of greenness on allergic rhinitis outcomes in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: The relationship between greenness and health emerges as new public health concern. More published studies from multiple areas have explored the relationship between greenness and allergic rhinitis (AR) in children and adolescents. This study aims to determine the association between greenness and allergic rhinitis by systematic review and meta-analysis, in order to provide a more comprehensive assessment of the impact of greenness on AR in children and adolescents. METHODS: The relative literature was systematically searched in PubMed, Embase, and Web of science lastly on September 25, 2022. Terms related to greenness and allergic rhinitis were used for searching. Summary effect estimates of greenness on AR in children and adolescents were calculated for per 10 % increase of greenness exposure with different buffer sizes by random-effects model. RESULTS: A total of 579 studies were screened, and fourteen studies from Europe, Asia and North America were finally included. Most greenness exposure were measured by normalized difference vegetation index (NDVI). Enhanced vegetation index, outdoor-green environmental score and existed to measuring different greenness types. Greenness surrounding residences and schools were assessed. The overall effect of greenness on primary outcome was 1.00 (95%CI = 0.99-1.00). Most effect estimates of greenness were included in the NDVI-500 m group, and the pooled OR was 0.99 (95%CI = 0.97-1.01). No significant pooled estimates were found in analyses with study locations. CONCLUSION: This study indicates no significant association between greenness exposure and AR in children and adolescents. Various exposure measures and conversion of data may affect the results of this meta-analysis. More precise assessment of personal greenness exposure in well-designed prospective studies are vital for drawing a definite association in future. Furthermore, greenness exposure surrounding schools should be paid considerable attention for its effect on AR in school-aged children and adolescents.

Altered gut fungi in systemic lupus erythematosus - A pilot study.

Objective: Gut fungi, as symbiosis with the human gastrointestinal tract, may regulate physiology via multiple interactions with host cells. The plausible role of fungi in systemic lupus erythematosus (SLE) is far from clear and need to be explored. Methods: A total of 64 subjects were recruited, including SLE, rheumatoid arthritis (RA), undifferentiated connective tissue diseases (UCTDs) patients and healthy controls (HCs). Fecal samples of subjects were collected. Gut fungi and bacteria were detected by ITS sequencing and 16S rRNA gene sequencing, respectively. Alpha and beta diversities of microbiota were analyzed. Linear discriminant analysis effect size analysis was performed to identify abundance of microbiota in different groups. The correlation network between bacterial and fungal microbiota was analyzed based on Spearman correlation. Results: Gut fungal diversity and community composition exhibited significant shifts in SLE compared with UCTDs, RA and HCs. Compared with HCs, the alpha and beta diversities of fungal microbiota decreased in SLE patients. According to principal coordinates analysis results, the constitution of fungal microbiota from SLE, RA, UCTDs patients and HCs exhibited distinct differences with a clear separation between fungal microbiota. There was dysbiosis in the compositions of fungal and bacterial microbiota in the SLE patients, compared to HCs. Pezizales, Cantharellales and Pseudaleuria were enriched in SLE compared with HCs, RA and UCTDs. There was a complex relationship network between bacterial and fungal microbiota, especially Candida which was related to a variety of bacteria. Conclusion: This study presents a pilot analysis of fungal microbiota with diversity and composition in SLE, and identifies several gut fungi with different abundance patterns taxa among SLE, RA, UCTDs and HCs. Furthermore, the gut bacterial-fungal association network in SLE patients was altered compared with HCs.

The Interaction Between Dietary Fructose and Gut Microbiota in Hyperuricemia and Gout.

With the worldwide epidemics of hyperuricemia and associated gout, the diseases with purine metabolic disorders have become a serious threat to human public health. Accumulating evidence has shown that they have been linked to increased consumption of fructose in humans, we hereby made a timely review on the roles of fructose intake and the gut microbiota in regulating purine metabolism, together with the potential mechanisms by which excessive fructose intake contributes to hyperuricemia and gout. To this end, we focus on the understanding of the interaction between a fructose-rich diet and the gut microbiota in hyperuricemia and gout to seek for safe, cheap, and side-effect-free clinical interventions. Furthermore, fructose intake recommendations for hyperuricemia and gout patients, as well as the variety of probiotics and prebiotics with uric acid-lowering effects targeting the intestinal tract are also summarized to provide reference and guidance for the further research.

Ambient air pollutants increase the risk of immunoglobulin E-mediated allergic diseases: a systematic review and meta-analysis.

Immunoglobulin E (IgE)-mediated allergic diseases, including eczema, atopic dermatitis (AD), and allergic rhinitis (AR), have increased prevalence in recent decades. Recent studies have proved that environmental pollution might have correlations with IgE-mediated allergic diseases, but existing research findings were controversial. Thus, we performed a comprehensive meta-analysis from published observational studies to evaluate the risk of long-term and short-term exposure to air pollutants on eczema, AD, and AR in the population (per 10-µg/m3 increase in PM2.5 and PM10; per 1-ppb increase in SO2, NO2, CO, and O3). PubMed, Embase, and Web of Science were searched to identify qualified literatures. The Cochran Q test was used to assess heterogeneity and quantified with the I2 statistic. Pooled effects and the 95% confidence intervals (CIs) were used to evaluate outcome effects. A total of 55 articles were included in the study. The results showed that long-term and short-term exposure to PM10 increased the risk of eczema (PM10, RRlong = 1.583, 95% CI: 1.328, 1.888; RRshort = 1.006, 95% CI: 1.003-1.008) and short-term exposure to NO2 (RRshort = 1.009, 95% CI: 1.008-1.011) was associated with eczema. Short-term exposure to SO2 (RRshort: 1.008, 95% CI: 1.001-1.015) was associated with the risk of AD. For AR, PM2.5 (RRlong = 1.058, 95% CI: 1.014-1.222) was harmful in the long term, and short-term exposure to PM10 (RRshort: 1.028, 95% CI: 1.008-1.049) and NO2 (RRshort: 1.018, 95% CI: 1.007-1.029) were risk factors. The findings indicated that exposure to air pollutants might increase the risk of IgE-mediated allergic diseases. Further studies are warranted to illustrate the potential mechanism for air pollutants and allergic diseases.

Proton pump inhibitors induce changes in the gut microbiome composition of systemic lupus erythematosus patients.

BACKGROUND: Currently, few studies focus on the association between gut microbiota and systemic lupus erythematosus (SLE), and much less studies consider the effect of drug usage. Proton pump inhibitors (PPIs) are commonly used to treat drug-related gastrointestinal damage in SLE patients. Therefore, the purpose of this study is to examine the gut microbiota of SLE patients using PPIs. METHODS: Fecal samples from 20 SLE patients with PPIs (P-SLE), 20 SLE patients without PPIs (NP-SLE) and 17 healthy controls (HCs) were obtained. The structure of the bacterial community in the fecal samples was analyzed by 16S rRNA gene sequencing. Redundancy analysis (RDA) was performed to observe the relationship between clinical variables and microbiome composition in P-SLE and NP-SLE patients. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, functional capabilities of microbiota were estimated. Network analysis was performed to analyze the association of metabolic pathway alterations with altered gut microbiota in P-SLE and NP-SLE patients. RESULTS: P-SLE patients exhibited increased alpha-diversity and an altered composition of the gut microbiota compared with NP-SLE patients. The alpha-diversity of NP-SLE patients was significantly lower than HCs but also of P-SLE patients, whose alpha-diversity had become similar to HCs. Compared with NP-SLE patients, the relative abundances of Lactobacillus, Roseburia, Oxalobacter, and Desulfovibrio were increased, while those of Veillonella, Escherichia, Morganella, Pseudomonas and Stenotrophomonas were decreased in P-SLE patients. RDA indicated that PPI use was the only significant exploratory variable for the microbiome composition when comparing SLE patients. KEGG analysis showed that 16 metabolic pathways were significantly different between NP-SLE and P-SLE patients. These metabolic pathways were mainly associated with changes in Escherichia, Roseburia, Stenotrophomonas, Morganella and Alipipes as determined by the network analysis. CONCLUSIONS: PPI use is associated with an improved microbiome composition of SLE patients as it 1) increases alpha-diversity levels back to normal, 2) increases the abundance of various (beneficial) commensals, and 3) decreases the abundance of certain opportunistic pathogenic genera such as Escherichia. Validation studies with higher patient numbers are however recommended to explore these patterns in more detail.

Temperature might increase the hospital admission risk for rheumatoid arthritis patients in Anqing, China: a time-series study.

Temperature has been studied in relation to many health outcomes. However, few studies have explored its effect on the risk of hospital admission for rheumatoid arthritis (RA). A distributed lag non-linear model (DLNM) was used to analyze associations between mean temperature, diurnal temperature range (DTR), temperature change between neighboring days (TCN), and daily admissions for RA from 2015 to 2019 in Anqing, China. Subgroup analyses based on age, gender, rheumatoid factors, and admission route were performed. In total, 1456 patients with RA were hospitalized. Regarding the cumulative-lag effects of extreme cold temperature (5th percentile = 3℃), the risks of admissions for RA were increased and highest at lag 0-11 (RR = 2.68, 95% CI: 1.23-5.86). Exposing to low (5th percentile = 1.9℃) and high (95th percentile = 14.2℃) DTRs both had increased risks of RA admission, with highest RRs of 1.40 (95% CI: 1.03-1.91) and 1.24 (95% CI: 1.0-1.53) at lag 0 day, respectively. As for TCN, the marginal risk of admission in RA patients was found when exposed to high TCN (95th percentile = 2.9℃) with the largest single-day effect at lag 10 (RR = 1.11, 95% CI: 1.01-1.23). In subgroup analyses, females were more susceptible to extreme cold temperature, low and high DTRs, and high TCN. In regard to extreme cold temperature, significant risk of hospital admission in females only appeared at lag 2 (RR = 1.48, 95% CI: 1.02-2.15) and lag 0-2 (RR = 2.35, 95% CI: 1.11-4.95). It is clear that RA patients exposed to changing temperature may increase risks of admission.

Antimalarials may reduce cancer risk in patients with systemic lupus erythematosus: a systematic review and meta-analysis of prospective studies.

OBJECTIVE: To investigate the effect of antimalarials on cancer risk in patients with systemic lupus erythematosus (SLE). METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched from their inception to October 3, 2020. Relative risk (RR) with 95% confidence intervals (CI) was used to evaluate the results. Subgroup analyses were used to assess heterogeneity. A funnel plot was used to explore publication bias. STATA was applied for all analyses. RESULTS: A total of nine studies consisted of four nested case-control, two case-cohort and three cohort studies were included. The results showed that antimalarials might reduce the risk of cancer in SLE (RR = 0.68, 95%CI: 0.55-0.85). In the subgroup analysis of four nested case-control and two case-cohort studies, the pooled RR was estimated as 0.69 (95% CI: 0.60-0.80). In four studies about hydroxychloroquine, the pooled RR was estimated as 0.70 (95% CI: 0.53-0.93). Antimalarials might reduce the risk of cancer in SLE among the Asian population (RR = 0.66; 95% CI: 0.49-0.88) (I2 = 43.1%, p = .173). And the consistent result was also found in SLE from multiple centres (RR = 0.72; 95%CI: 0.60-0.87) (I2 = 0%, p = .671). On disease course- and comorbidities-matched studies, the pooled RRs were 0.69 (95% CI: 0.52-0.93) and 0.59 (95% CI: 0.46-0.75), respectively. CONCLUSION: Results of this meta-analysis showed that antimalarial drugs might be protective factors for cancer in SLE. Hydroxychloroquine might be a protective factor for cancer in SLE patients.KEY MESSAGESAntimalarials might be protective factors for cancer in SLE.Hydroxychloroquine might be a protective factor for cancer in SLE patients.The first article to perform the meta-analysis of antimalarial drugs on the risk of cancer in SLE patients.

Periodontitis Exacerbates and Promotes the Progression of Chronic Kidney Disease Through Oral Flora, Cytokines, and Oxidative Stress.

Periodontitis is a type of systemic immune inflammation that is caused by the complex infection of a variety of microorganisms in the subgingival plaque and the imbalance of the microbial ecological environment in the mouth. Periodontitis and chronic kidney disease (CKD) share many risk factors, such as obesity, smoking, and age. A growing body of data supports a strong correlation between periodontitis and kidney disease. Evidence supports the role of periodontal inflammation and elevated serum inflammatory mediators in renal atherosclerosis, renal deterioration, and end-stage renal disease (ESRD) development. Periodontitis is a risk factor for kidney disease. However, to our knowledge, there are few studies detailing the possible link between periodontitis and CKD. This review summarizes the possible mechanisms underlying periodontitis and CKD. More importantly, it highlights novel and potential pathogenic factors for CKD, including bacteria, pro-inflammatory mediators and oxidative stress. However, most research on the relationship between periodontitis and systemic disease has not determined causality, and these diseases are largely linked by bidirectional associations. Future research will focus on exploring these links to contribute to new treatments for CKD.

Systemic lupus erythematosus patients have a distinct structural and functional skin microbiota compared with controls.

OBJECTIVE: The skin is the second most affected organ after articular involvement in systemic lupus erythematosus (SLE) patients. Cutaneous involvement occurs in approximately 80% of patients during the course of SLE. Interaction between the host and skin microorganism is a complex process. There are few studies on the diversity of skin microbes in SLE patients. Therefore, this study aims to explore the relationship between skin microorganisms and SLE. METHODS: A total of 20 SLE patients, 20 controls with rosacea and 20 healthy controls were selected as study subjects. Both the skin microbiota of rash region and non-rash region for each SLE patient were collected.16S rRNA gene sequencing was used to detected skin microbiota from 80 specimens. α-Diversity and ß-diversity of skin microbiota were analyzed based on operational taxonomic units (OTUs) and minimal entropy decomposition (MED). Using Wilcoxon test and Linear Discriminate Analysis Effect Size (LEfSe), skin microbial diversity and composition were analyzed. Functional capabilities of microbiota were estimated through Kyoto Encyclopedia of Genes and Genomes database. RESULTS: Compared to rash region of SLE, diversity and richness were increased in healthy controls, and decreased in non-rash region of SLE and rash region of controls with rosacea. Additionally, changes of skin microbial composition were found at different taxonomic levels between four groups. For example, genus Halomonas was increased and genera Pelagibacterium, Novosphingobium, and Curvibacter were decreased in rash region compared to non-rash region of SLE based on OTUs and MED. Based on OTUs, metabolic pathways were also found differences in SLE patients, such as Xenobiotics Biodegradation and Metabolism. CONCLUSION: Compositions and diversity of skin microbiota in SLE patients are changed. This pilot study provides some suggestive evidence for further exploration of skin microbiota in SLE patients with cutaneous involvement.

Verification of SARS-CoV-2-Encoded small RNAs and contribution to Infection-Associated lung inflammation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. SARS-CoV-2 is a positive-stranded RNA virus belongs to Coronaviridae family. The viral genome of SARS-CoV-2 contains around 29.8 kilobase with a 5'-cap structure and 3'-poly-A tail, and shows 79.2% nucleotide identity with human SARS-CoV-1, which caused the 2002-2004 SARS outbreak. As the successor to SARS-CoV-1, SARS-CoV-2 now has circulated across the globe. There is a growing understanding of SARS-CoV-2 in virology, epidemiology, and clinical management strategies. In this study, we verified the existence of two 18-22 nt small viral RNAs (svRNAs) derived from the same precursor in human specimens infected with SARS-CoV-2, including nasopharyngeal swabs and formalin-fixed paraffin-embedded (FFPE) explanted lungs from lung transplantation of COVID-19 patients. We then simulated and confirmed the formation of these two SARS-CoV-2-Encoded small RNAs in human lung epithelial cells. And the potential pro-inflammatory effects of the splicing and maturation process of these two svRNAs in human lung epithelial cells were also explored. By screening cytokine storm genes and the characteristic expression profiling of COVID-19 in the explanted lung tissues and the svRNAs precursor transfected human lung epithelial cells, we found that the maturation of these two small viral RNAs contributed significantly to the infection associated lung inflammation, mainly via the activation of the CXCL8, CXCL11 and type I interferon signaling pathway. Taken together, we discovered two SARS-CoV-2-Encoded small RNAs and investigated the pro-inflammatory effects during their maturation in human lung epithelial cells, which might provide new insight into the pathogenesis and possible treatment options for COVID-19.

The oral and gut microbiome in rheumatoid arthritis patients: a systematic review.

BACKGROUND: Recently, researchers have proposed a possible relationship between RA and the microbiome of the oral cavity and gut. However, this relation has not been systematically established. Herein, we conducted a comprehensive review of the pertinent literature to describe this possible association. METHODS: We systematically performed searches in databases, namely EMBASE, the Cochrane Library, and PubMed, from inception to 7 June 2020 to identify case-control studies that compared the oral and gut microbiome in adult RA patients with those of controls. The primary outcome was specific bacterial changes between RA and controls. The secondary outcome was microbial diversity changes between RA and controls. RESULTS: In total, 26 articles were considered eligible for inclusion and reported some differences. Therein, ≥3 articles reported decreased Faecalibacterium in the gut of early-RA (ERA)/RA patients compared with healthy controls (HCs). Also, ≥3 articles reported decreased Streptococcus and Haemophilus and increased Prevotella in the oral cavity of ERA/RA patients compared with HCs. In addition, some Prevotella species, including P. histicola and P. oulorum, showed increased trends in RA patients' oral cavity, compared with HCs. The α-diversity of the microbiome was either increased or not changed in the oral cavity of RA patients, but it was more commonly either decreased or not changed in the gut of RA patients. CONCLUSIONS: In this systematic review, we identified the microbiome associated with RA patients in comparison with controls. More research is needed in the future to find the deep relationship between RA and the microbiome.

Comparative of the Effectiveness and Safety of Biological Agents, Tofacitinib, and Fecal Microbiota Transplantation in Ulcerative Colitis: Systematic Review and Network Meta-Analysis.

BACKGROUND: Biological agents are commonly used for the treatment of ulcerative colitis (UC). As new treatments, tofacitinib, and fecal microbiota transplantation (FMT) have demonstrated efficacy in treating UC. This network meta-analysis aims to determine the efficacy and safety of biological agents, tofacitinib, and FMT. METHODS: A network meta-analysis was conducted by systematically searching the PubMed, Embase, and Cochrane Libraries. According to strict inclusion and exclusion criteria, we included randomized controlled trials (RCTs) of biological agents, tofacitinib, and FMT in UC. A random-effect model was chosen by the network meta-analysis and sensitivity analysis. Heterogeneity test and publication bias test were performed to determine the efficacy of treatments. RESULTS: Data were extracted from 16 RCTs and we found that all treatments were more effective than the placebos. A total of 21 comparisons were made to determine efficiency. We found that infliximab, vedolizumab, and FMT performed better curative effect in terms of absolute effects and relative ranks. Furthermore, there was no statistical difference in the efficacy of biological agents, tofacitinib, and FMT. Moreover, no treatments were found to increase the occurrence of adverse events when compared with placebos, except infliximab. However, vedolizumab seemed to reduce the occurrence of adverse events compared with infliximab. CONCLUSION: Of the biological agents, vedolizumab and infliximab were the most effective, suggesting that biological agents are still a better choice. Nevertheless, tofacitinib and FMT may be promising alternatives with high efficacies. However, more safety and maintenance studies need to be conducted in future for the acquisition of more accurate results.Abbreviations: FMT: Fecal microbiota transplantation; UC: Ulcerative colitis; RCTs: Randomized controlled trials; IBD: Inflammatory bowel disease; CD: Crohn's disease; IBS: Irritable bowel syndrome; CDI: Clostridium difficile infections; ITT: Intention-to-treat; RR: Relative risk; CI: Confidence interval; CrI: Credible intervals; IFX: Infliximab; ADA: Adalimumab; TFB: Tofacitinib; GLM: Golimumab; VDZ: Vedolizumab; PBO: Placebo; wk: week; F: Female; M: Male; AEs: Adverse events; SAEs: Serious adverse events; anti-TNF: Anti-tumor necrosis factors.

"Smoking paradox" is not true in patients with ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Ischemic stroke (IS) is a common cause of death from vascular diseases. Studies have found that smoking increases the risk of ischemic stroke, but the association of smoking with the outcome of IS remains unclear. This meta-analysis aims to investigate the effect of smoking on the prognosis of IS. METHODS: We searched four electronic databases including PubMed, EMBASE, Cochrane library and Web of science for papers, published before January 2019. In this meta-analysis, Review Manager 5.3 software was used to calculate for the pooled estimate effect, as well as the inverse-variance method for pooled mean difference (MD) and odds ratio (OR) of incidence in two groups of population. RESULTS: A total of 14,789 citations were identified during the literature search, 21 studies were included in the meta-analyses after screening. The full-adjusted OR of poor prognostic outcome in smoking and nonsmoking patients with stroke was pooled as 0.96 (95% CI 0.77-1.21), suggested that smoking or not has no impact on prognosis of IS. The pooled MD of onset age between smoking and nonsmoking IS patients was - 10.05 (- 12.91, - 7.19), indicated that smoking causes first onset of IS to occur 10 years earlier. CONCLUSIONS: This meta-analysis showed that smoking was not a protective factor for poor prognosis of IS. Smoking patients with IS are 10 years younger than nonsmoking patients at time of the first onset of stroke.

Efficacy and safety of bismuth-containing quadruple treatment and concomitant treatment for first-line Helicobacter pylori eradication: A systematic review and meta-analysis.

Bismuth-containing quadruple treatment (BQT) and concomitant treatment (CT) were recommended as alternative first-line treatments of Helicobacter pylori (H. Pylori). A meta-analysis was performed to evaluate the cure rates and compare efficacy and safety of BQT and CT for H. Pylori eradication. PubMed, Cochrane Library, and Embase databases were searched on June 16, 2020. Meta-analysis, sensitivity analysis, and subgroup analysis were conducted by Review Manager 5.3 and Stata 11.0. Ten studies were collected. We found no difference of cure rate between BQT and CT in intention-to-treat (ITT) analysis (84.6% vs. 82.9%, OR = 1.14, 95% CI: 0.94-1.38; P = 0.19) and marginally statistical difference in per-protocol (PP) analysis (92.4% vs 90.1%, OR = 1.32, 95% CI: 1.00-1.73; P = 0.05). Based on the results of subgroup analyses, we found statistical difference of eradication rate between BQT and CT (amoxicillin + clarithromycin + metronidazole + PPI treatment) according to PP analysis (94.3% vs. 91.5%, OR = 1.49, 95% CI:1.03-2.15; P = 0.03) and marginally statistical difference according to ITT analysis (87.5% vs. 84.6%, OR = 1.28, 95% CI:1.00-1.65; P = 0.05). BQT and CT may be both good treatment options for H. pylori infection. However, BQT was superior to current scheme of CT (amoxicillin + clarithromycin + metronidazole + PPI treatment) in subgroup analysis. It is very necessary to choose tailored therapy as an outstanding way to reduce the impact of antibiotic.

Flipped classroom improves nursing students' theoretical learning in China: A meta-analysis.

OBJECTIVE: At present, current didactic teaching delivery method help nursing students apply theory to clinical situations in an inefficient way. The flipped classroom (FC), a novel teaching mode emphasizing self-study and critical thinking, has generated interest in nursing education in China. However, there are a gap in the literature and no consistent outcomes of current studies which compared FC and lecture-based learning (LBL), and no systematic review has comprehensively compared theoretical scores as an affected outcome in FC versus LBL modes. METHODS: In this review, we analyze flipped-learning nursing students' scores, and aim to assess the efficacy and provide a deeper understanding of the FC in nursing education. Following the inclusion criteria, articles were obtained by searching PubMed, Embase and Chinese data, including the China National Knowledge Infrastructure, Wanfang Data, and VIP database until 3 January 2020. Data were extracted from eligible articles and quality was assessed. A meta-analysis was then performed using a random effects model with a standardized mean value (SMD) and a 95% confidence interval (CI).32 studies were included after reviewing 2,439 citations. All studies were randomized controlled trials (RCTs). The FC theoretical knowledge scores in FC were significantly positively affected compared to those of the traditional classroom (SMD = 1.33, 95% CI: 1.02-1.64; P < 0.001). In addition, 23 studies reported skill scores, indicating significant difference between the FC mode and LBL mode (SMD = 1.58, 95%CI: 1.23-1.93; P < 0.001). CONCLUSIONS: The results of this meta-analysis suggest that compared to the LBL teaching method, the FC mode dose significantly improve Chinese nursing students' theoretical scores. However, the problems of heterogeneity and publication bias in this study need to be remedied high-quality future studies.