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Human epidermal growth factor receptor (EGFR) is involved in strong association with malignant proliferation, which has been shown to play a central role in the development and progression of non-small cell lung cancer and other solid tumors. The tumor-suppressor protein MIG6 is a negative regulator of EGFR kinase activity by binding at the activation interface of asymmetric dimer of EGFR kinase domain to disrupt EGFR dimerization and then inactivate the kinase. The protein adopts two discrete fragments 1 and 2 to directly interact with EGFR. It is revealed that the MIG6 fragment 2 is intrinsically disordered in free unbound state, but would fold into a well-structured β-hairpin when binding to EGFR, thus characterized by a so-called coupled folding-upon-binding process, which can be regarded as a compromise between favorable direct readout and unfavorable indirect readout. Here, a 23-mer F2P peptide was derived from MIG6 fragment 2, trimmed into a 17-mer tF2P peptide that contains the binding hotspot region of the fragment 2, and then constrained with an ordered hairpin conformation in free unbound state by disulfide stapling, finally resulting in a rationally stapled/trimmed stF2P peptide that largely minimizes the unfavorable indirect readout effect upon its binding to EGFR kinase domain, with affinity improved considerably upon the trimming and stapling/trimming. These rationally designed β-hairpin peptides may be further exploited as potent anti-lung cancer agents to target the activation event of EGFR dimerization.

Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic molecular targets for severe asthma in neutrophils using bioinformatics analysis.Fifteen healthy controls and 3 patients with neutrophilic severe asthma were screened from the Gene Expression Omnibus (GEO) database. Based on the analysis of differentially expressed genes (DEGs), functional and pathway enrichment analyses, gene set enrichment analysis, protein-protein interaction network construction, and analysis were performed. Moreover, small-molecule drug candidates have also been identified.Three hundred and three upregulated and 59 downregulated genes were identified. Gene ontology function enrichment analyses were primarily related to inflammatory response, immune response, leukocyte migration, neutrophil chemotaxis, mitogen-activated protein kinase cascade, Jun N-terminal kinase cascade, I-kappaB kinase/nuclear factor-κB, and MyD88-dependent toll-like receptor signaling pathway. Pathway enrichment analyses and gene set enrichment analysis were mainly involved in cytokine-cytokine receptor interaction, the TNF signaling pathway, leukocyte transendothelial migration, and the NOD-like receptor signaling pathway. Furthermore, 1 important module and 10 hub genes (CXCL8, TLR2, CXCL1, ICAM1, CXCR4, FPR2, SELL, PTEN, TREM1, and LEP) were identified in the protein-protein interaction network. Moreover, indoprofen, mimosine, STOCK1N-35874, trapidil, iloprost, aminoglutethimide, ajmaline, levobunolol, ethionamide, cefaclor, dimenhydrinate, and bethanechol are potential drugs for the treatment of neutrophil-predominant severe asthma.This study identified potential biomarkers, pathogenesis, and therapeutic molecular targets for neutrophil-predominant severe asthma.

Dieulafoy's disease is characterized by abnormal submucosal arteries and results in acute luminal hemorrhage. Dieulafoy's lesions can also be found in the submucosa of the bronchus. Due to its low incidence rate and non-specific clinical symptoms, Dieulafoy's disease is easy to overlook, but can lead to massive bleeding and high rates of mortality. Therefore, improvements in the understanding of the disease are necessary. The awareness of the disease and associated diagnostic and treatment techniques have continued to improve, and thus, an increasing number of cases of Dieulafoy's disease of the bronchus have been reported. In the present review, 74 cases of Dieulafoy's disease are summarized. New technologies such as endobronchial ultrasound, narrow-band imaging, angiography and argon plasma treatment have been found to be increasingly applied to diagnose and treat Dieulafoy's disease of the bronchus. Therefore, the primary focus of this systematic review is to highlight advances in the diagnosis and treatment of bronchial Dieulafoy's disease.

Baduanjin is a traditional Chinese exercise regimen used to treat various chronic illnesses and is associated with both psychological and physical benefits. However, its benefits for patients suffering from chronic obstructive pulmonary disease (COPD) are unclear. This study aims to assess the efficacy, safety, and underlying mechanisms of Baduanjin exercise in patients with moderate-to-severe COPD (BROCADE) by remote monitoring.This study protocol describes a multicenter, open-label, prospective randomized computed tomography. A total of 150 individuals who meet the inclusion criteria after the screening and consent processes will take part in the study. All participants will be provided routine medication and lifestyle interventions. They will be randomly assigned to a control group, a classical pulmonary rehabilitation group, or a Baduanjin group, which will undergo remotely monitored Baduanjin exercises for a cumulative duration of 1 hour per day, three times per week for 12 weeks. The participants will be followed for 24 weeks. The primary outcomes will be a 6-minutes walking distance and St. George's Respiratory Questionnaire index. The secondary outcomes will be lung function, cross-sectional area of the pectoralis major and subcutaneous fat, modified Medical Research Council score, COPD assessment test questionnaire results, extremity muscle strength, and quality of life. Any adverse events that may occur will be monitored and recorded.This study is ongoing and will be submitted to a peer-reviewed journal for publication once completed.A novel neutrophil-related inflammatory mechanism will potentially be identified. In addition, the study results will provide a safe, effective, simple and operational Baduanjin exercise protocol for moderate-to-severe COPD patients aimed at improving prognosis and quality of life.

Severe neutrophilic asthma is often characterized by persistent airway inflammation and irreversible airway remodeling, which are overstimulated by the high-mobility group box protein 1 (HMGB1). Although wogonin, an O-methylated flavone, has been widely used to treat inflammatory and allergic diseases, its therapeutic effects and potential mechanisms on severe neutrophilic asthma remain elusive.To evaluate whether wogonin alleviates airway neutrophilia through inducing neutrophil apoptosis and attenuates airway smooth muscle cells (ASMCs) proliferation and migration.The effect of wogonin on reducing neutrophilic airway inflammation, including neutrophil infiltration and inflammatory mediators, was examined in a mouse model of severe neutrophilic asthma sensitized with ovalbumin and lipopolysaccharide. Also, the effect of wogonin on inducing human neutrophil apoptosis was manifested using cellular morphology, flow cytometry, and caspase inhibition assays. Furthermore, the effect of wogonin on inhibiting HMGB1-mediated ASMCs proliferation and migration was determined.Wogonin reduced the frequency of neutrophils and inhibited the production of multiple inflammatory mediators, including ovalbumin-specific IgE, tumor necrosis factor-α, interleukin-6, and HMGB1, in bronchoalveolar lavage fluid and lung tissues of the neutrophilic asthmatic mouse model. These data strongly support a significantly suppressed neutrophilic airway inflammation, functionally consistent to the relieved airway hyperresponsiveness by wogonin in vivo. Wogonin induced human neutrophil apoptosis in a dose-dependent manner by activating caspase-8 and caspase-3 in vitro. Wogonin pretreatment abolished HMGB1-induced ASMCs proliferation and migration, which can be explained by the inhibition of phosphorylation in the mitogen-activated protein kinase (MAPK) /Akt singling pathways.Our findings demonstrate that wogonin augments caspase-dependent apoptosis in neutrophils to alleviate neutrophilic inflammatory responses and regulates intracellular signaling to inhibit HMGB1-mediated ASMCs activation, providing a promising therapeutic agent for severe neutrophilic asthma.

The incidence of hypoxic pulmonary hypertension (HPH) is increasing. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in HPH, but the functions and mechanism have yet to be fully elucidated. In the present study, we established a HPH rat model with 8 h of hypoxia exposure (10% O2) per day for 21 days. High-throughput sequencing identified 60 differentially expressed (DE) lncRNAs, 20 DE miRNAs and 695 DE mRNAs in rat lung tissue. qRT-PCR verified the accuracy of the results. The DE mRNAs were significantly enriched in immune response, inflammatory response, leukocyte migration, cell cycle, cellular response to interleukin-1, IL-17 signalling pathway, cytokine–cytokine receptor interaction and Toll-like receptor signalling pathway. According to the theory of competing endogenous RNA (ceRNA) networks, lncRNA–miRNA–mRNA network was constructed by Cytoscape software, 16 miRNAs and 144 mRNAs. The results suggested that seven DE lncRNAs (Ly6l, AABR07038849.2, AABR07069008.2, AABR07064873.1, AABR07001382.1, AABR07068161.1 and AABR07060341.2) may serve as molecular sponges of the corresponding miRNAs and play a major role in HPH.

BACKGROUND miR-214-3p has been found to inhibit proliferation and migration in cancer cells. The objective of this study was to determine whether ARHGEF12 is involved in miR-214-3p-mediated suppression of proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). MATERIAL AND METHODS PASMCs were cultured under normoxia or hypoxia. miR-214-3p mimics or inhibitors were transiently transfected into PASMCs. Proliferation, apoptosis, and migration of PASMCs were evaluated using MTT assay, flow cytometry, and Boyden chamber apparatus. Western blot analysis was used to examine expression of Rho guanine nucleotide exchange factor 12 (ARHGEF12), c-fos, c-jun, and caspase-3. Luciferase reporter assay was used to test the direct regulation of miR-214-3p on the 3'-untranslated region (UTR) of ARHGEF12. RESULTS miR-214-3p was significantly upregulated in hypoxia-treated PASMCs. Knockdown of miR-214-3p significantly attenuated hypoxia-induced proliferation and migration in PASMCs and promoted apoptosis, whereas this effect was aggravated by overexpression of miR-214-3p. In addition, dual-luciferase reporter assay demonstrated that ARHGEF12 is a direct target gene of miR-214-3p. The protein levels of ARHGEF12 were downregulated after knockdown of miR-214-3p in PASMCs. Rescue experiment results indicated that decreased proliferation of PASMCs resulted from knockdown of miR-214-3p were partially reversed by silencing of ARHGEF12 by siRNA. Furthermore, knockdown of miR-214-3p reduced expression of c-jun and c-fos, but increased expression of caspase-3 in PASMCs under hypoxia. CONCLUSIONS In conclusion, these results indicate that miR-214-3p acts as a novel regulator of hypoxia-induced proliferation and migration by directly targeting ARHGEF12 and dysregulating c-jun and c-fos in PASMCs, and may be a potential therapeutic target for treating pulmonary hypertension.

Autophagy is an important mechanism for cellular self-digestion and basal homeostasis. This gene- and modulator-regulated pathway is conserved in cells. Recently, several studies have shown that autophagic dysfunction is associated with pulmonary hypertension (PH). However, the relationship between autophagy and PH remains controversial. In this review, we mainly introduce the effects of autophagy-related genes and some regulatory molecules on PH and the relationship between autophagy and PH under the conditions of hypoxia, monocrotaline injection, thromboembolic stress, oxidative stress, and other drugs and toxins. The effects of other autophagy-related drugs, such as chloroquine, 3-methyladenine, rapamycin, and other potential therapeutic drugs and targets, in PH are also described.

Background: Liuzijue is a traditional Qigong exercise that is commonly performed in China. However, the treatment effects of Liuzijue Qigong are controversial. The aim of this systematic review was to evaluate the efficacy of Liuzijue Qigong in patients with chronic obstructive pulmonary disease (COPD). Methods: Randomised controlled trials were identified by searching several English and Chinese databases from inception to August 8, 2020. Study selection and data extraction were independently performed by two investigators. Data synthesis and analysis were carried out with Review Manager software 5.2. Quality assessment for each study was based on the modified Jadad scale. Results: Forty studies with 3137 participants were included. Significant improvements were observed in the following outcomes (mean difference, 95% confidence interval): forced expiratory volume in 1 s (0.17, 0.09–0.25) and its percent predicted normal value (6.04, 3.43–8.65), forced expiratory volume in 1 s to forced volume capacity ratio (6.95, 3.06–10.83), 6-min walking distance (33.06, 23.73–42.38), 30-s sit-to-stand test (2.65, 0.98–4.32), COPD assessment test score (− 2.04, − 2.77 to − 1.30), modified Medical Research Council dyspnea scale (− 0.34, − 0.48 to − 0.20), Medical Research Council dyspnea scale (− 0.37, − 0.57 to − 0.18), Traditional Chinese Medicine syndrome score (− 1.85, − 2.86 to − 0.85), Hamilton Anxiety Scale (− 2.31, − 3.04 to − 1.59), Hamilton Depression Scale (− 2.08, − 2.45 to − 1.71) and St. George’s Respiratory Questionnaire (− 6.94, − 9.20 to − 4.67). Conclusions: Liuzijue Qigong may be an effective adjuvant therapy for the improvement of lung function, exercise capacity, health status, mental status and quality of life in patients with COPD.

BACKGROUNDRemdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial.METHODSWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046).RESULTSData of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05–1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44–0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63–0.94], I2 = 0.0%, P = 0.716).CONCLUSIONRemdesivir is efficacious and safe for the treatment of COVID-19.TRIAL REGISTRATION NUMBERThis study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).

BACKGROUND Fractures are a major public health problem for elderly people throughout the world. Anemia is also a common, important health problem among elderly populations. The aim of this article was to estimate the association between anemia and fracture incidence via a systematic review and meta-analysis. MATERIAL AND METHODS The participant, intervention, observation, and study design (PICOS) reporting guidelines were followed, and databases were searched from their inception to May 2020 to identify relevant studies. When heterogeneity was significant, and a random-effects model was used. Subgroup analysis was conducted to explore the source of heterogeneity based on sex, study design, and region. RESULTS We found that anemia significantly increased fracture risk [relative risk (RR)=1.26, 95% confidence interval (CI)=1.14-1.39, P

To explore potential critical genes and identify circular RNAs (circRNAs) that act as the competitive endogenous RNA (ceRNA) in a hypoxic pulmonary hypertension (HPH) rat model. Constructed rat model, and a bioinformatics method was used to analyse differentially expressed (DE) genes and construct a circRNA-miRNA-mRNA ceRNA regulatory network. Then, qRT-PCR was used to verify. The significant DEcircRNAs/DEmiRNAs/DEmRNAs was showed, and a ceRNA network with 8 DEcircRNAs, 9 DEmiRNAs and 46 DEmRNAs were constructed. The functional enrichment suggested the inflammatory response, NF-κB signalling, MAPK cascade and Toll-like receptor were associated with HPH. Further assessment confirmed that circ_002723, circ_008021, circ_016925 and circ_020581 could have a potential ceRNA mechanism by sponging miR-23a or miR-21 to control downstream target gene and be involved in the pathophysiology of HPH. The qRT-PCR validation results were consistent with the RNA-Seq results. This study revealed potentially important genes, pathways and ceRNA regulatory networks in HPH.

We conduct a study to explore the influence of impaired renal function on prognosis in Acute pulmonary embolism (APE) patients. A meta-analysis was performed using the EMBASE and PubMed databases for relevant publications reporting the impact of impaired renal function on the clinical outcomes in patients with APE. Eventually, 17 articles were included in our analysis. The results suggested that renal insufficiency (RI) is a predictor of poor prognosis in APE patients(short-term mortality: pooled OR = 2.83, 95%CI: 2.20���3.63; long-term mortality: pooled OR = 2.30, 95%CI: 1.72���3.08; adverse outcomes: pooled OR = 3.02, 95%CI: 2.60���3.51). The short-term and long-term mortality rates of APE patients with RI were both higher than those in patients without RI. In addition, acute kidney injury(AKI) could serve as a predictive factor of poor prognosis (pooled OR = 2.75, 95%CI: 2.45���3.08), and it doubles the overall mortality rate in APE patients. However, chronic kidney disease (CKD) did not predict poor prognosis in APE patients (pooled OR = 1.94, 95%CI: 0.99���3.81), although it could slightly increase the overall mortality rate in APE patients. RI and AKI could be included in the prognosis evaluation for APE, but the impact of CKD in APE patients has yet to be determined.

ObjectiveTo assess the relationship between opioid therapy for chronic noncancer pain and fracture risk by a meta-analysis of cohort studies and case-control studies.MethodsThe included cohort studies and case-control studies were identified by searching the PubMed and EMBASE databases from their inception until May 24, 2019. The outcome of interest was a fracture. This information was independently screened by two authors. When the heterogeneity among studies was significant, a random effects model was used to determine the overall combined risk estimate.ResultsIn total, 12 cohort studies and 6 case-control studies were included. We used the Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included literature, and 14 of the studies were considered high-quality studies. The overall relative risk of opioid therapy and fractures was 1.78 (95% confidence interval (CI) 1.53 - 2.07). Subgroup analyses revealed sources of heterogeneity, sensitivity analysis was stable, and no publication bias was observed.ConclusionsThe meta-analysis showed that the use of opioids significantly increased the risk of fracture.

Background To determine the association of lymphatic vessel density (LVD) with the prognosis of Asian non-small cell lung cancer (NSCLC) patients via a meta-analysis. Methods Eligible studies were selected by searching PubMed and EMBASE from inception to July 25, 2017. The reference lists of the retrieved articles were also consulted. The information was independently screened by two authors. When heterogeneity was significant, a random-effects model was used to determine overall pooled risk estimates. Results A total of 15 studies with 1075 patients were finally included in the meta-analysis. LVD was positively associated with the prognosis of NSCLC in the overall analysis (hazard ratio (HR) 1.14, 95% confidence interval (95% CI): 1.02–1.27, p = 0.000, I2 = 73.2%). Subgroup analyses were performed on 5 VEGFR-3 groups (p = 0.709, I2 = 0.0%), 3 LYVE-1 groups (p = 0.01, I2 = 86.4%), 5 D2–40 groups (p = 0.019, I2 = 66.2%), and 2 podoplanin groups (p = 0.094, I2 = 64.5%). Sensitivity analysis indicated robust results. There was no publication bias. Conclusions LVD is an indicator of poor prognosis in Asian NSCLC patients.

Objectives Patients with pulmonary embolism (PE) have a higher red cell distribution width (RDW), which may complicate the interpretation of the prognosis of PE. We aim to evaluate the diagnostic utility of the RDW in patients with PE. Methods Eligible studies were identified by searching PubMed and EMBASE from inception to December 23, 2018. The data were pooled using Stata 12 to evaluate the prognostic value. The sources of heterogeneity were detected. Results For the analysis of prognosis, 7 studies with 2146 patients were included, with median RDW values ranging from 13.4% to 15.7% and a median cut-off point of 18.27%. A total of 247 patients (11.5% mortality) among the 2146 participants died. Overall, RDW was positively associated with the prognosis of PE in the overall analysis (HR = 1.19, 95% CI = 1.10-1.29, I2 = 73.4%; P = 0.000). Subgroup analyses by study design, sex and follow-up time indicated that they were not sources of heterogeneity. Conclusions An elevated RDW has the potential to be a biomarker for prognosis in PE patients.

Phosphatase and tensin homolog (PTEN) plays an important role in the pathogenesis of hypoxic pulmonary hypertension (HPH). A decrease in PTEN expression is associated with the hypermethylation of its promoter. However, whether the demethylation of the PTEN gene could attenuate HPH remains unknown. 5-Aza-2'-deoxycytidine (5-Aza-dC) is a DNA methyltransferase (DNMT) inhibitor. The present study was designed to investigate the effects and mechanisms of 5-Aza-dC on HPH. The proliferation, migration and apoptosis of rat pulmonary artery smooth muscle cells (PASMCs) induced by hypoxia and treated with 5-Aza-dC were detected. The expression of PTEN and DNMTs and the PTEN methylation status of PASMCs were detected. SD rats were randomly divided into normal group, hypoxia group and hypoxia + 5-Aza-dC group. The expression of PTEN was decreased, the expression of DNMTs was increased, and the methylation status of PTEN was increased in hypoxia-induced PASMCs. However, 5-Aza-dC can rescue the decreased PTEN, inhibit DNMT levels in a dose-dependent manner and suppress PTEN methylation. Furthermore, the demethylation of PTEN, which was induced by 5-Aza-dC, inhibited the proliferation, migration and promoted apoptosis in PASMCs. In vivo studies further demonstrated that the expression of PTEN, mean pulmonary artery pressure and right ventricular hypertrophy index in HPH rats was attenuated by 5-Aza-dC. 5-Aza-dC also suppressed the expression of DNMTs and PTEN methylation in the lungs of HPH rats. These results indicated that PTEN promoter methylation status is involved in HPH. 5-Aza-dC, as a DNMT inhibitor, has the potential to attenuate HPH via demethylation of the PTEN promoter.

The reconstruction of pulmonary vascular structure caused by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) is the central link in the formation of pulmonary arterial hypertension (PAH). Platelet‑derived growth factor (PDGF) can regulate the proliferation and migration of PASMCs. At the same time, nuclear factor of activated T cells (NFATs) plays an important role in the development of PAH. To the best of our knowledge, there are no reports yet regarding whether PDGF regulates NFATc2 to increase the proliferation of PASMCs. The present study aimed to investigate whether PDGF affects the proliferation and migration of PASMCs by regulating NFAT, and to study the pathogenesis of PAH. PASMCs were treated with recombinant PDGF; Cell Counting Kit‑8 and clone formation experiments showed that PDGF enhanced the cell viability and proliferation of PASMCs. Cell cycle distribution and molecular markers related to cell proliferation (cyclin D1, CDK4 and Proliferating Cell Nuclear Antigen) were detected by flow cytometry, and the results indicated that PDGF promoted the division of PAMSCs. The scratch migration and Transwell migration assays showed that the migratory ability of PASMCs was enhanced following PDGF treatment. Changes in NFATs (NFATc1‑5) after PDGF treatment were evaluated by reverse transcription‑quantitative PCR and western blotting; NFATc2 showed the most significant results. Finally, PDGF‑treated cells were treated with an NFAT pathway inhibitor, cyclosporin A, or a small interfering RNA targeting NFATc2, and changes in cell proliferation and migration were evaluated to assess the role of NFATc2 in PDGF‑induced cell proliferation and migration. In conclusion, PDGF may regulate PASMC proliferation and migration by regulating the expression of NFAT, further leading to the occurrence of PAH. It is proposed that NFATc2 could be used as a potential target for PAH treatment.

Elevated red blood cell distribution width (RDW) may correlate with a worse prognosis in pulmonary hypertension (PH), though results to date are inconsistent. The goal of this study is to detect the impact of RDW on the prognosis of PH.PubMed and EMBASE databases were searched from their inception to July 22, 2019 for relevant publications reporting the relationship between RDW and the prognosis of PH. A meta-analysis was performed, and the heterogeneity across the included studies was evaluated using I and Q statistics. We conducted sensitivity and subgroup analyses to detect sources of heterogeneity. In addition, potential publication bias was evaluated by Begg's and Egger's tests.In total, 1236 publications were retrieved, and 7 eligible publications with 666 PH patients were included in our meta-analysis. The results suggested that increased RDW can predict worse prognosis in PH (hazard ratio (HR) = 1.27, 95% confidence interval (CI) 1.11-1.45). According to subgroup analysis, study design, region, various endpoints, time of follow-up, and patient age were not sources of heterogeneity. In addition, RDW showed prognostic value in retrospective studies (HR = 1.32, 95%CI 1.15-1.51) but not in prospective studies (HR = 1.14, 95%CI 0.78-1.67). Additionally, RDW may serve as a predictive biomarker of PH in Europe (HR = 1.33, 95%CI 1.18-1.49) but not in Asia (HR = 1.20, 95%CI 0.90-1.58). Further analysis indicated that the prognostic value of RDW was influenced by patient age (>44 years: HR = 1.34, 95%CI 1.17-1.55; ≤44 years: HR = 1.20, 95%CI 0.90-1.58) and follow-up (

[This corrects the article DOI: 10.1371/journal.pone.0181852.].

The association between abdominal obesity (as measured by waist circumference (WC) and waist-to-hip ratio (WHR)) and colorectal cancer (CRC) has not been fully quantified, and the magnitude of CRC risk associated with abdominal obesity is still unclear. A meta-analysis of prospective studies was performed to elucidate the CRC risk associated with abdominal obesity. Pubmed and Embase were searched for studies assessing the association between abdominal obesity and CRC risk. Relative risks (RRs) with 95% confidence intervals (95% CIs) were pooled using random-effects model of meta-analysis. Nineteen prospective cohort studies from eighteen publications were included in this meta-analysis. A total of 12,837 CRC cases were identified among 1,343,560 participants. Greater WC and WHR were significantly associated with increased risk of total colorectal cancer (WC: RR 1.42, 95% CI 1.30, 1.55; WHR: RR 1.39, 95% CI 1.25, 1.53), colon cancer (WC: RR 1.53, 95% CI 1.36, 1.72; WHR: 1.39, 95% CI 1.18, 1.63), and rectal cancer (WC: RR 1.20, 95% CI 1.03, 1.39; WHR: RR 1.22, 95% CI 1.05, 1.42). Subgroup analyses further identified the robustness of the association above. No obvious risk of publication bias was observed. In summary, abdominal obesity may play an important role in the development of CRC.

Supplemental Digital Content is available in the text, Background: Cancer morbidity and mortality are growing rapidly worldwide. There have been an increasing number of studies on the correlation between miRNA1246 expression in circulating blood and tumors; however, no comprehensive conclusion has been reached. Therefore, this meta-analysis was carried out to systematically evaluate the diagnostic value of blood levels of microRNA-1246 for malignant tumors. Methods: We searched PubMed, MEDLINE, Embase, The Cochrane Library, the China National Knowledge Internet (CNKI), and Wanfang databases from the inception of each database until November 2018. The quality of the included literature was evaluated using the quality assessment tool called Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The data were pooled using Stata14 and Meta-DiSc 1.4 software. Results: Seven studies were included. The pooled sensitivity (SENS) was 0.80 (95% CI 0.65–0.89), the pooled specificity (SPEC) was 0.77 (95% CI 0.70–0.83), the pooled positive likelihood ratio (PLR) was 3.55 (95% CI 2.53–4.99), the pooled negative likelihood ratio (NLR) was 0.26 (95% CI 0.16–0.47), the pooled diagnostic odds ratio (DOR) was 13.78 (95% CI 5.84–32.5), and the area under the curve (AUC) was 0.83 (95% CI 0.79–0.86). The result of Deeks’ funnel plot was P = 0.31, indicating a lack of publication bias. Conclusion: MicroRNA-1246 in the blood can be used as a good indicator for the diagnosis of malignant tumor diseases and has a moderate diagnostic accuracy for the differentiation of patients with malignant tumors from healthy people.

Objective This study aimed to elucidate the effects of cholecystectomy on the risk of colorectal cancer (CRC) by conducting a meta-analysis of 10 cohort studies. Methods The eligible cohort studies were selected by searching the PubMed and EMBASE databases from their origination to June 30, 2016, as well as by consulting the reference lists of the selected articles. Two authors individually collected the data from the 10 papers. When the data showed marked heterogeneity, we used a random-effects model to estimate the overall pooled risk; otherwise, a fixed effects model was employed. Results The final analysis included ten cohort studies. According to the Newcastle-Ottawa Scale (NOS), nine papers were considered high quality. After the data of these 9 studies were combined, an increased risk of CRC was found among the individuals who had undergone cholecystectomy (risk ratio (RR) 1.22; 95% confidence interval (CI) 1.08–1.38). In addition, we also found a promising increased risk for colon cancer (CC) (RR 1.30, 95% CI 1.07–1.58), but no relationship between cholecystectomy and rectum cancer (RC) (RR 1.09; 95% CI 0.89–1.34) was observed. Additionally, in the sub-group analysis of the tumor location in the colon, a positive risk for ascending colon cancer (ACC) was found (RR 1.18, 95% CI 1.11–1.26). After combining the ACC, transverse colon cancer (TCC), sigmoid colon cancer (SCC) and descending colon cancer (DCC) patients, we found a positive relationship with cholecystectomy (RR 1.18, 95% CI 1.11–1.26). Furthermore, after combining the ACC and DCC patients, we also found a positive relationship with cholecystectomy (RR 1.28; 95% CI 1.11–1.26) in the sub-group analysis. In an additional sub-group analysis of patients from Western countries, there was a positive relationship between cholecystectomy and the risk of CRC (RR 1.20; 95% CI 1.05–1.36). Furthermore, a positive relationship between female gender and CRC was also found (RR 1.17; 95% CI 1.03–1.34). However, there was no relationship between gender and CC or RC. Furthermore, no publication bias was observed, and the sensitivity analysis indicated stable results. Conclusions This meta-analysis of 10 cohort studies revealed that cholecystectomy is associated with an increased risk for CRC, CC and ACC, particularly in Western countries. No relationship between cholecystectomy and RC was observed. There was no relationship between gender and either CC or RC, but a positive relationship between female gender and CRC was observed.