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.

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.

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.

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.

Strong policies control the spread of COVID-19 in China.

The coronavirus disease 2019 (COVID-19) outbroke in Wuhan, Hubei Province, China, affecting more than 200 countries and regions. This study aimed to predict the development of the epidemic with specific interventional policies applied in China and evaluate their effectiveness. COVID-19 data of Hubei Province and the next five most affected provinces were collected from daily case reports of COVID-19 on the Health Committee official website of these provinces. The number of current cases, defined as the number of confirmed cases minus the number of cured cases and those who have died, were examined in this study. A modified susceptible-exposed-infectious-removed (SEIR) model was used to assess the effects of interventional policies on the epidemic. In this study, 28 January was day 0 of the model. The results of the modified SEIR model showed that the number of current cases in Hubei and Zhejiang provinces tended to be stabilized after 70 days and after 60 days in the four other provinces. The predicted number of current cases without policy intervention was shown to far exceed that with policy intervention. The estimated number of COVID-19 cases in Hubei Province with policy intervention was predicted to peak at 51 222, whereas that without policy intervention was predicted to reach 157 721. Based on the results of the model, strong interventional policies were found to be vital components of epidemic control. Applying such policies is likely to shorten the duration of the epidemic and reduce the number of new cases.

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.

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.

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.

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.

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.

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.

Dysbiosis of oral microbiota is associated with systemic lupus erythematosus.

OBJECTIVE: The important role of intestinal microbiota in systemic lupus erythematosus (SLE) has been recognized. Oral-gut microbiome axis is a crucial link in human health and disease, but few researches indicated the relationship between oral microorganisms and SLE. This study mainly explored the composition and changes of oral microorganisms in SLE patients with different stages, clinical manifestations and biomarkers. DESIGN: Oral microbiota was detected by 16S ribosomal RNA gene sequencing from 20 SLE patients and 19 healthy controls (HCs). The evenness, diversity and composition of oral microbiota were analyzed. Moreover, receiver-operating characteristic analysis was conducted. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to investigate microbiota functions. RESULTS: The oral microbiota of SLE patients was imbalanced and the diversity was decreased, but no difference was found between new-onset and treated SLE patients. Families Lactobacillaceae, Veillonellaceae and Moraxellaceae were enriched in SLE patients. Families like Corynebacteriaceae, Micrococcaceae, Defluviitaleaceae, Caulobacteraceae, Phyllobacteriaceae, Methylobacteriaceae, Hyphomicrobiaceae, Sphingomonadaceae, Halomonadaceae, Pseudomonadaceae, Xanthomonadaceae, etc. were decreased in SLE patients. After multiple testing adjustment, families Sphingomonadaceae, Halomonadaceae, and Xanthomonadaceae were significantly decreased in SLE patients. And area under the curve was 0.953 (95% confidence intervals 0.890-1.000) to distinguish SLE patients from HCs. There were differences in metabolic pathways between SLE and HCs (P = 0.025). CONCLUSIONS: These findings collectively support that oral microbiota dysbiosis and aberrant metabolic pathways were observed in patients with SLE. Our findings may provide suggestive evidences for the diagnosis and treatment of SLE.