Vitamin D supplementation during pregnancy and the risk of wheezing in offspring: a systematic review and dose-response meta-analysis.

Background: In the past few years, growing evidence supports a preventive role of vitamin D supplementation during pregnancy for wheezing or asthma in offspring. However, the optimal dose of vitamin D intake is unclear. We conducted a meta-analysis to examine the linear and nonlinear dose-response pattern of vitamin D intake during pregnancy and asthma or wheezing in offspring. Questions/purposes: The purpose of this study was to answer the following question: Which dose of vitamin D is more effective in preventing wheezing in offspring? Method: We identified relevant studies by searching PubMed, EMBASE and CENTRAL up to December 2017 and by hand-searching reference lists. Meta-analysis and subgroup analysis were performed. Fixed or random effects model linear trends analyses were conducted based on the heterogeneity test. Then, if the data did not show linear trends, we considered a nonlinear trend analysis instead. Results: A total of 6068 participants were included in the study. Our analysis showed an inverse relationship between the intake of vitamin D during pregnancy and the occurrence of wheezing in offspring (pooled OR = 0.68, 95% CI = 0.55-0.83, I2 = 24%, Z statistic = 3.64, p < 0.01). We found a nonlinear U-shaped association between vitamin D supplementation during pregnancy and asthma or wheezing in offspring, with the lowest risk at approximately 800 IU/d. Publication bias was shown in a funnel plot without Egger's test. Conclusions: Vitamin D intake during pregnancy is inversely related to wheezing or asthma in offspring. Furthermore, the trend analysis indicates that offspring may benefit from approximately 800 IU/d vitamin D intake during pregnancy.

Azithromycin or erythromycin? Macrolides for non-cystic fibrosis bronchiectasis in adults: A systematic review and adjusted indirect treatment comparison.

Non-cystic fibrosis (non-CF) bronchiectasis is a condition characterized by an airway inflammatory response to bacterial pathogens. Frequent exacerbations have a major influence on the quality of life. Macrolide antibiotics have not only antibacterial but also immune-regulation effects. It is proved that macrolides have a benefit in preventing exacerbations. However, it is still uncertain whether azithromycin or erythromycin is more effective and safe. The purpose of this study was to answer the following question: Which kind of macrolide antibiotic is more effective and safe in preventing non-CF bronchiectasis exacerbation? We conducted a systematic review to identify randomized clinical trials published up to May 2017 that reported on macrolides for non-CF bronchiectasis and an adjusted indirect treatment comparison (AITC) between macrolides to evaluate their efficacy and safety. The direct comparison meta-analysis found that macrolides decreased the rate of exacerbation of non-CF bronchiectasis (risk ratio (RR) = 0.45; 95% confidence interval (CI) 0.36-0.55) with heterogeneity ( I2 = 63.7%, p = 0.064). The AITC showed that azithromycin had a significantly lower bronchiectasis exacerbation rate than erythromycin (RR = 0.35; 95% CI: 0.403-0.947). Azithromycin increased the risk of diarrhea and abnormal pain. This meta-analysis suggested that long-term treatment with macrolides significantly reduced the incidence of non-CF bronchiectasis exacerbation. Moreover, azithromycin is more efficient than roxithromycin and erythromycin in preventing exacerbation.

Study on the mechanism of inhibition of Escherichia coli by Polygonum capitatum based on network pharmacology and molecular docking technology: A review.

This study aims to analyze the effective components of Polygonum capitatum (PC) inhibiting Escherichia coli based on network pharmacology methods and predict its molecular mechanism of action. PC compounds and targets were collected from the TCMSP database, Swiss Target Prediction, and the literature. E coli targets were searched using the GeneCards database. The targets of E coli and the targets of the active ingredients of PC were taken as intersections to obtain the intersecting targets. The resulting overlapping targets were uploaded to the STRING database to construct the protein interaction network diagram of E coli target inhibition. The key targets for the inhibitory effect of PC on E coli were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by uploading key targets into the DAVID database. The results showed that there were 50 targets for PC to inhibit E coli. Among them, there are 5 core targets, mainly including AKT1, TNF, EGFR, JUN, and ESR1. A total of 196 gene ontology functional analysis results and 126 Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis results were obtained. These include cellular response to cadmium-ion, cellular response to reactive oxygen species, pathways in cancer, prostate cancer, and PI3K-Akt signaling pathway. Molecular docking results indicate that Lutedin, Hirsutin, Flazin, and Ellagic acid in PC have high affinity for the target genes AKT1, TNF, MAPK3 and EGFR. PC exerts its inhibitory effect on E coli through multi-targets and multi-pathways, which provides a new basis for the new use of PC as an old medicine.

Mechanism of Simiao Decoction in the treatment of atherosclerosis based on network pharmacology prediction and molecular docking.

To explore the molecular mechanism of Simiao Decoction (SMD) intervening atherosclerosis (AS). The main components and potential mechanisms of SMD remain unknown. This study aims to initially clarify the potential mechanism of SMD in the treatment of AS based on network pharmacology and molecular docking techniques. The principal components and corresponding protein targets of SMD were searched on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the compound-target network was constructed by Cytoscape3.9.1. AS targets were searched on DrugBank, OMIM, and TTD databases. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a protein-protein interaction network. We further performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the targets. The molecular docking method was used to verify the interaction between core components of SMD and targets. We created the active compounds-targets network and the active compounds-AS-targets network based on the network database containing Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, DrugBank, OMIM, and TTD. We discovered that the therapy of AS with SMD involves 3 key substances-quercetin, kaempferol, and luteolin-as well as 5 crucial targets-ALB, AKT1, TNF, IL6, and TP53. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the shared targets involved a number of signaling pathways, including the advanced glycosylation end product-receptor of AGE signaling pathway in diabetic complications, Hepatitis B, Lipid and atherosclerosis, Chemical Carcinogenesis-Receptor Activation, and Pathways in Cancer. The molecular docking demonstrated that the binding energies of quercetin, kaempferol, and luteolin with 5 important targets were favorable. This study reveals the active ingredients and potential molecular mechanism of SMD in the treatment of AS, and provides a reference for subsequent basic research.

Association of vitamin D receptor gene polymorphism with the risk of sepsis: A systematic review and meta-analysis.

BACKGROUND: To investigate the association between sepsis and the vitamin D receptor (VDR) gene polymorphisms. METHODS: Databases including PubMed, Cochrane Library, EMbase, CNKI, Wanfang Data, and VIP Data were systematically searched. The association was assessed using odds ratios (ORs), and 95% confidence intervals (CIs). The statistical tests were performed using Review Manager 5.4. RESULTS: We identified a total of 5 studies. The relationship between VDR gene polymorphisms (Apa I, Bsm I, Taq I, and Fok I), and incidence of sepsis was investigated. The results of this meta-analysis showed that the allelic contrast model (F vs f, P = .03, OR = 0.65, 95% CI = 0.44-0.95), dominant genetic model (FF vs Ff + ff, P = .02, OR = 0.53, 95% CI = 0.30-0.91), and codominance genetic model (FF vs ff, P = .03, OR = 0.39, 95% CI = 0.16-0.91) of VDR Fok I locus increased the risk of sepsis, and the lack of association between the VDR Fok I gene polymorphism and the risk assessment of sepsis, based on the ethnic subgroup analysis, might be attributable to the small sample size. The risk of sepsis with Apa I, Bsm I, and Taq I did not appear to be correlated. CONCLUSION SUBSECTIONS: This meta-analysis revealed that the VDR Fok I polymorphism is closely associated with the susceptibility to sepsis, and patients with sepsis have lower 25-hydroxyvitamin D levels. VDR Fok I gene mutations may change the risk of sepsis.

Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain.

Neuropathic pain (NeP) remains a significant clinical challenge owing to insufficient awareness of its pathological mechanisms. We elucidated the aberrant metabolism of the cerebral cortex in NeP induced by the chronic constriction injury (CCI) using metabolomics and proteomics analyses. After CCI surgery, the values of MWT and TWL markedly reduced and maintained at a low level. CCI induced the significant dysregulation of 57 metabolites and 31 proteins in the cerebral cortex. Integrative analyses showed that the differentially expressed metabolites and proteins were primarily involved in alanine, aspartate and glutamate metabolism, GABAergic synapse, and retrograde endocannabinoid signaling. Targeted metabolomics and western blot analysis confirmed the alterations of some key metabolites and proteins in endogenous pain-modulatory system. In conclusion, our study revealed the alterations of endocannabinoids system and purinergic system in the CCI group, and provided a novel perspective on the roles of endogenous pain-modulatory system in the pathological mechanisms of NeP.

Vitamin D can ameliorate premature ovarian failure by inhibiting neutrophil extracellular traps: A review.

The etiology of premature ovarian failure (POF) is mainly related to inflammatory diseases, autoimmune diseases, and tumor radiotherapy and chemotherapy; however, its specific pathogenesis has not been clarified. Vitamin D (VD), a fat-soluble vitamin, is an essential steroid hormone in the human body. Neutrophil extracellular traps (NETs) are meshwork structures that are formed when neutrophils are stimulated by inflammation and other factors and are closely associated with autoimmune and inflammatory diseases. Notably, VD inhibits NET formation and intervenes in the development of POF in terms of inflammatory and immune responses, oxidative stress, and tissue fibrosis. Therefore, this study aimed to theorize the relationship between NETs, VD, and POF and provide new ideas and targets for the pathogenesis and clinical treatment of POF.

Mechanism of Polygonum capitatum intervention in pulmonary fibrosis based on network pharmacology and molecular docking technology: A review.

Pulmonary fibrosis (PF) is a serious interstitial disease that includes diffuse collagen deposition of lung tissue. Polygonum capitatum Buch.-Ham. ex D. Don (THL) is a traditional vaccine that has antibacterial and anti-inflammatory effects. In this research, to investigate the mechanism of action of THL in the intervention of pulmonary fibrosis by network pharmacology and molecular docking related research methods, in order to provide a theoretical basis for expanding the scope of THL medication. A total of 49 active ingredients were analyzed and screened in Cephalus cephalusis, including 35 pulmonary fibrosis targets, and 10 key targets such as ALB, EGFR were screened after software analysis. The molecular docking results showed that there were 44 binding energies less than -3 kcal·mol-1 in the 60 docking results, indicating that most proteins had strong binding energies with compounds. The key targets of KEGG enrichment analysis were mainly enriched in 20 core action pathways, such as hemostasis-related pathway, regulation of kinase activity. This study shows that based on network pharmacology, the multicomponent-multitarget-multipathway effect of THL intervention in pulmonary fibrosis is discussed.

Astragalus polysaccharide protects sepsis model rats after cecum ligation and puncture.

To investigate the protective effect and mechanism of Astragalus polysaccharide (APS) on septic rats, the present project applied APS at concentrations of 400, 600, and 800 mg/kg/d to rats for prophylactic administration for 7 d, and a rat sepsis model was constructed by the cecum ligation and puncture (CLP) method. Forty-eight rats were divided into six groups of eight each. Each experiment was repeated at least three times. Rat serum levels of VD3, 25(OH)D3, 1,25(OH)2D3, IL-6, TNF-α, CRP, sICAM-1, corticosterone (CORT), and short-chain fatty acids (SCFAs) in each group were detected, and renal damage was observed by H&E. We also determined the protein expression of CYP27B1, CYP24A1, vitamin D receptor (VDR), steroidogenic acute regulatory protein (STAR), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), CYP21A2, CYP17A1, and CYP11B1. An operational taxonomic unit (OTU) was used to determine the gut microbiota diversity of septic rats after prophylactic administration and before modeling. Results revealed that APS markedly increased the contents of 25(OH)D3 and 1,25(OH)2D3 but greatly decreased those of TNF-α, IL-6, CRP, sICAM-1, and CORT. APS alleviated renal tubular dilation and vascular congestion in rat kidneys and substantially reduced renal cell apoptosis. Moreover, the expression of CYP24A1, VDR, CYP11B1, CYP21A2, CYP17A1, STAR, and 3ß-HSD in the kidneys of the H-APS group was substantially decreased compared to that of the model group, whereas CYP27B1 was markedly increased. GC-MS detection indicated a substantial increase in SCFAs and acetic acid content in the H-APS group versus model group. Through 16S sequencing, the abundance of genus and gut microbiota species increased in the APS groups compared to that of the control group. Taken together, APS increased the activity of the vitamin D axis, inhibited the production of inflammatory factors in the body, altered the structure of rat intestinal flora, and increased the amount of acetic acid and SCFAs in rats, thereby effectively hindering inflammation and organ damage in septic rats.

Ankylosing spondylitis disease activity and serum vitamin D levels: A systematic review and meta-analysis.

BACKGROUND: To prove that serum vitamin D (VD) levels are strongly associated with ankylosing spondylitis (AS) disease activity, the association between serum VD levels and key monitoring indicators of AS disease activity has been analyzed, such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). METHODS: Studies published in PubMed, Cochrane Library, EMBASE, and China National Knowledge Infrastructure by August 30, 2022 were searched, and 6 studies finally met the selection criteria. Serum 25-hydroxyvitamin D (25(OH)D), ESR, CRP levels, and correlation coefficients between serum VD and BASDAI, ESR, CRP in AS, and control in these studies were extracted for the meta-analysis. RESULTS: When compared to controls, patients with AS had considerably lower blood 25(OH)D levels (MD = -7.53 ng/mL, 95% CI, -9.78 to -5.28, P < .001) and significantly higher ESR and CRP levels (ESR: MD = 11.75 mm/h, 95% CI, 4.20 to 19.31, P = .002; CRP: MD = 15.36 mg/L, 95% CI, 4.95 to 25.77, P = .004). Additionally, a negative correlation was discovered between serum VD levels and BASDAI, ESR, and CRP (Fisher' Z = -0.34, -0.38, -0.35, respectively). CONCLUSION: The findings of our meta-analysis demonstrated a negative correlation between serum VD levels and the main monitoring indices of disease activity in patients with AS and verified that the differences in the continent and ethnicity may be one of the major contributors to this finding.

The pathogenesis and treatment mechanism of Parkinson's disease from the perspective of traditional Chinese medicine.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease with no treatment currently available to modify its progression. Traditional Chinese medicine (TCM) has gained attention for its unique theoretical basis and clinical effects. Many studies have reported on the clinical effects and pharmacological mechanisms of Chinese herbs in PD. However, few studies have focused on the treatment mechanisms of anti-PD TCM drugs from the perspective of TCM itself. PURPOSE: To elaborate the treatment mechanisms of anti-PD TCM drugs in the perspective of TCM. METHODS: We performed a literature survey using traditional books of Chinese medicine and online scientific databases including PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), and others up to July 2021. RESULTS: TCM theory states that PD is caused by a dysfunction of the zang-fu organs (liver, spleen, kidney, and lung) and subsequent pathogenic factors (wind, fire, phlegm, and blood stasis). Based on the pathogenesis, removing pathogenic factors and restoring visceral function are two primary treatment principles for PD in TCM. The former includes dispelling wind, clearing heat, resolving phlegm, and promoting blood circulation, while the latter involves nourishing the liver and kidney and strengthening the spleen. The anti-PD mechanisms of the active ingredients of TCM compounds and herbs at different levels include anti-apoptosis, anti-inflammation, and anti-oxidative stress, as well as the restoration of mitochondrial function and the regulation of autophagy and neurotransmitters. CONCLUSION: Chinese herbs and prescriptions can be used to treat PD by targeting multiple pharmacological mechanisms.

Mechanisms of Dendrobium officinale polysaccharides in repairing gastric mucosal injuries based on mitogen-activated protein kinases (MAPK) signaling pathway.

The present study aimed to investigate the protective effects and molecular mechanisms of Dendrobium officinale polysaccharides on gastric mucosal injuries. Following one week of continuous intragastric administration, a gastric mucosal injury model was established using intragastric administration of anhydrous ethanol. The area of gastric ulcer was measured, the contents of interleukin- 6 (IL-6), epidermal growth factor receptor (EGFR), and thyroid transcription factor 1 (TFF-1) in serum were detected by enzyme linked immunosorbent assay (ELISA), and the expressions of EGFR, TFF-1, IL-6, Raf-2, MAP kinase kinase 1 (MEK1), MEK2, and ERK1 in the gastric tissue were determined utilizing qPCR, Western blotting and immunohistochemistry. Simultaneously, Dendrobium officinale polysaccharides and anhydrous ethanol were added to the gastric mucosal cells (GES1) cultured in vitro, and the protective effects of Dendrobium officinale polysaccharides on cell viability was detected using Cell Counting Kit (CCK)-8. The addition of Dendrobium officinale polysaccharides markedly improved the gastric epithelial defect, inflammatory cell infiltration, and redness and swelling stemmed from gastric mucosal injuries and greatly reduced the area of gastric ulcer. The inhibition rates of gastric ulcer were 48.12 ± 2.98, 42.95 ± 1.52, and 27.96 ± 2.05% in the high, medium, and low concentration Dendrobium officinale polysaccharide groups, respectively. Dendrobium officinale polysaccharides could increase the expressions of EGFR and TFF-1 and decrease the expressions of IL-6, Raf-2, MEK1, MEK2, and ERK1. Dendrobium officinale polysaccharides could reduce the level of inflammatory factors and protect gastric mucosa by inhibiting the expression of MAPK pathway genes and proteins.

Inhibitory effect of Astragalus Membranaceus on osteoporosis in SAMP6 mice by regulating vitaminD/FGF23/Klotho signaling pathway.

Spontaneous senile osteoporosis severely threatens the health of the senior population which has emerged as a severe issue for society. A SAMP6 mouse model was utilized to estimate the impact of intragastrically administered Astragalus Membranaceus (AR) on spontaneous senile osteoporosis. Bone mineral density (BMD) and bone microstructure were measured using Micro-CT; contents of calcium and phosphorus were determined with the colorimetric method; and gene and protein expressions of fibroblast growth factor 23 (FGF23), Klotho, Vitamin D receptor (VDR), CYP27B1 and CYP24A1 were detected using qPCR, Western blot and ELISA assays, respectively. The findings indicated that AR could improve the femoral BMD and bone microstructure, elevate the contents of calcium and phosphorus, and increase the expression of Klotho, VDR, and CYP27B1 whereas decreasing the expression of FGF23 and CYP24A1 in SAMP6 mice in a dose independent manner. The present study has demonstrated that AR can promote osteogenesis and alleviate osteoporosis. It is also expected to provide a new insight for the treatment of spontaneous senile osteoporosis and to serve as a research basis for AR application.

Astragaloside alleviates alcoholic fatty liver disease by suppressing oxidative stress.

Alcoholic fatty liver disease (AFLD) is the most common liver disease and can progress to fatal liver cirrhosis and carcinoma, affecting millions of patients worldwide. The functions of astragaloside on the cardiovascular system have been elucidated. However, its role in AFLD is unclear. Ethanol-treated AML-12 cells were used as a cell model of alcoholic fatty liver. Real-time quantitative reverse transcription-PCR and Western blotting detected genes and proteins expressions. Reactive oxygen species (ROS), triglyceride, total cholesterol, low-density lipoprotein, albumin, ferritin, bilirubin, superoxide dismutase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were examined using commercial kits. Lipid accumulation was assessed by Oil red O staining. MTT and flow cytometry measured cell viability and apoptosis. JC-1 was used to analyze mitochondrial membrane potential. A rat model of AFLD was established by treating rats with ethanol. Astragaloside suppressed ethanol-induced lipid accumulation, oxidative stress, and the production of AST and ALT in AML-12 cells. Ethanol induced TNF-α and reduced IL-10 expression, which were reversed by astragaloside. Ethanol promoted Bax expression and cytochrome C release and inhibited Bcl-2 and ATP expression. Astragaloside hampered these apoptosis effects in AML-12 cells. Impaired mitochondrial membrane potential was recovered by astragaloside. However, all these astragaloside-mediated beneficial effects were abolished by the ROS inducer pyocyanin. Ethanol-induced activation of NF-κB signaling was suppressed by astragaloside in vitro and in vivo, suggesting that astragaloside inhibited oxidative stress by suppressing the activation of NF-κB signaling, thus improving liver function and alleviating AFLD in rats. Our study elucidates the pharmacological mechanism of astragaloside and provides potential therapeutic strategies for AFLD.

Astragalus improve aging bone marrow mesenchymal stem cells (BMSCs) vitality and osteogenesis through VD-FGF23-Klotho axis.

To clarify the regulation of astragalus on the aging BMSCs model and the effect of astragalus on Vitamin D (VD)-FGF23-Klotho axis. siRNA was used to interfere the expression of VDR gene in aging BMSCs. Serum containing astragalus in different concentrations was added to the cultured cells. The expression of osteocalcin and alkaline phosphatase were detected by alizarin red staining and ELISA. Cell vitality was detected by flow cytometry, CCK-8 test, and ß-galactosidase staining. The expression of FGF23, Klotho, CYP27B1, and CYP24A1 was detected by qRT-PCR and western blot. The results showed that after reducing VDR gene expression, the aging BMSCs model showed decreased activity and osteogenic ability, increased expression of FGF23, Klotho and CYP24A1, and decreased expression of CYP27B1. After adding serum-containing astragalus, the activity of cells and the osteogenic ability was increased; the expression levels of FGF23, Klotho and CYP24A1 were decreased, the expression levels of CYP27B1 were increased, and the trend was more obvious with the increase of astragalus concentration. This study confirmed that astragalus could inhibit the aging of BMSCs and improve the osteogenesis ability by regulating the VD-FGF23-Klotho pathway. This study provided a certain research basis for the therapeutic of traditional Chinese medicine (TCM) on primary osteoporosis.

Efficacy and Safety of Aidi Injection as an Adjuvant Therapy on Advanced Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Aidi injection (ADI) is being used widely for breast cancer in China. However, the efficacy and safety of it need to be summarized. We conducted a systematic review and meta-analysis to compare ADI and non-ADI treatment for advanced breast cancer. METHODS: We searched PubMed, EMBASE, CNKI, SinoMed, and CENTRAL from inception to Jan 2020 for randomized controlled trials (RCTs) with diagnosis of advanced breast cancer that compared the efficacy of ADI with non-ADI treatment. Two researchers screened the literature, extracted data, and evaluated risk of bias separately. The primary outcomes were overall response rate (ORR) and disease control rate (DCR). The secondary outcomes included the QOL, immune cells, and adverse events. Review Manager software was used for estimating risks of bias of included studies, data analysis, and plotting. The sensitivity analysis and the publication bias test were performed using the R language. I 2 and chi-square tests were used to estimate heterogeneity. If P > 0.1 or I 2 < 40%, the fixed-effect model meta-analysis was performed. A random or fixed-effect analysis was used depending on the heterogeneity testing. Weighted mean difference (WMD) or standard mean difference (SMD) was used for analysis of continuous data, and the rate ratio (RR) was calculated for the dichotomous variable, respectively. RESULTS: We included 14 studies with 1006 patients diagnosed as advanced breast cancer in total. The pooled effect showed that ADI increased ORR in advanced BC patients as an add-on therapy with little heterogeneity (RR = 1.14, 95% CI 1.03-1.27). DCR in BC patients could not be improved by ADI. ADI improved the KPS score in BC patients compared with chemotherapy alone (MD = 3.26, 95% CI 1.74-4.78). There were no improvements on immune markers except CD4/CD8 and NK%. Serum tumor markers CEA and CA153 were decreased while treated with ADI, but only one trial was involved. ADI decreased the numbers of myelosuppression in advanced BC patients, and AST, ALT, γ-GT, and CK-MB were all decreased. The sensitivity evaluation indicated that the result of the pooled effect size had good stability. CONCLUSION: This meta-analysis suggested that based on the existing evidence, treatment with ADI significantly changed the ORR of patients with advanced BC and improved their quality of life with few side effects. However, more randomized trials involving larger samples should be considered, and detailed mechanisms are needed to be uncovered.

Association of Metformin Use with Asthma Exacerbation in Patients with Concurrent Asthma and Diabetes: A Systematic Review and Meta-Analysis of Observational Studies.

Background: Asthma and diabetes are both diseases that affect a wide range of people worldwide. As a common treatment for diabetes, metformin has also been reported to be effective in improving asthma outcomes. We conducted a combined analysis to examine the efficacy of metformin in reducing asthma exacerbation in patients with concurrent asthma and diabetes. Methods: We searched the PubMed, Embase, and CENTRAL databases for articles published prior to April 2020 to find observational studies of individuals with concurrent asthma and diabetes that compared the risk of asthma exacerbation between metformin users and nonusers. Two researchers separately screened the studies, extracted data, and evaluated the risk of bias. The primary outcome was the adjusted risk of asthma exacerbation. The secondary outcomes were the adjusted risk of asthma-related hospitalization and emergency room visits. Review Manager was used for data analysis and plotting. I 2 and χ 2 tests were used to estimate heterogeneity. A random effects or fixed effects model was used depending on the heterogeneity. Odds ratios were calculated for dichotomous variables. Results: We included two studies with a total of 25252 patients. The pooled effect size showed that metformin was inversely associated with a risk of asthma exacerbation (OR = 0.65, 95% CI 0.28-1.48; χ 2 = 5.42, P=0.02; I 2 = 82%), asthma-related emergency department visits (OR = 0.81, 95% CI 0.74-0.89; χ 2 = 0.36, P=0.55; I 2 = 0%), and hospitalizations (OR = 0.43, 95% CI 0.14-1.29; χ 2 = 4.01, P=0.05; I 2 = 75%). Conclusion: This meta-analysis suggested that metformin decreased the risk of asthma-related emergency room visits for patients with concurrent asthma and diabetes. Metformin reduced the risk of asthma-related hospitalization and exacerbation but was not statistically significant. More randomized trials involving larger samples should be considered, and the mechanisms of these effects need to be fully elucidated.