Comprehensive analysis of the gut microbiota in patients with chronic obstructive pulmonary disease of varying severity-A prospective, observational study.

Accumulating evidence has highlighted the influence of the gut microbiota on lung immunity. We examined the effects of changes in intestinal microecology on the development of Chronic Obstructive Pulmonary Disease (COPD) and identified microbial biomarkers for acute exacerbations of COPD (AECOPD). Fecal samples were collected from 30 patients with stable COPD, 30 patients with AECOPD, and 10 healthy individuals. Fecal microbiological profiles were analyzed using 16S rRNA gene sequencing. The results showed a distinct difference in the bacterial community composition between the AECOPD, COPD, and healthy control groups. The COPD and AECOPD groups had higher levels of Firmicutes but lower levels of Bacteroidetes compared to the healthy control group at the phylum level. At the genus level, there was an increased abundance of Lachnoclostridium, Alistipes, Streptococcus, and Prevotella in COPD and AECOPD patients. Increasing levels of Lachnoclostridium and Prevotella may indicate an acute exacerbation of COPD. This study identified specific microbial biomarkers associated with AECOPD and characterized the composition of gut microbiota in patients with AECOPD.

Prediction of exacerbation frequency of AECOPD based on next-generation sequencing and its relationship with imbalance of lung and gut microbiota: a protocol of a prospective cohort study.

INTRODUCTION: Patients with frequent acute exacerbation phenotype chronic obstructive pulmonary disease (AECOPD) have a higher hospitalisation rate than infrequent exacerbation, the disease progresses quickly and treatment is more difficult. At present, it is impossible to predict patients with COPD with frequent acute exacerbation phenotypes. The composition of the lower respiratory tract flora and the intestinal flora is closely related to AECOPD, but the specific association mechanism between them is not very clear. This study used metagenomic next-generation sequencing (mNGS) technology to explore the microbial characteristics of the intestinal tract and airways of patients with COPD, and analyse the correlation between the sequencing results and inflammatory factors, immune factors and nutritional factors. METHODS AND ANALYSIS: This will be a prospective cohort study. We intend to recruit 152 patients with stable COPD. In the baseline, we will detect the participants' induced sputum and faecal flora through mNGS, and changes in blood immune levels, and the patient's condition is evaluated. Every 2 months, we will check the number of acute exacerbation through the phone range. After 12 months, we will check again the changes in the blood immune level, evaluate the patient's condition and count the number of episodes. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee of Guangdong Provincial Hospital of Traditional Chinese Medicine (approval number ZF2019-219-03). The results of the study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (ChiCTR2000032870).

Knockdown of metadherin inhibits cell proliferation and migration in colorectal cancer.

Metadherin (MTDH) is a multifunctional oncogene involved in tumor cell migration and metastasis through regulating a number of oncogenic signaling pathways in various human malignancies. Previous studies have demonstrated that MTDH is overexpressed in human colorectal cancer (CRC) and associated with cancer progression and a poor prognosis. However, the underlying mechanisms remain largely unknown. The present study investigated the expression and role of MTDH in CRC cells as well as the underlying mechanism of this. Western blot analysis and quantitative polymerase chain reaction were conducted to determine protein and mRNA expression of MTDH in three human CRC cell lines. A short hairpin RNA (shRNA) targeting MTDH was introduced into CRC HCT116 cells to stably inhibit MTDH expression. A Cell Counting Kit­8 assay, colony formation assay, Transwell assay and flow cytometry were used to investigate the effect of MTDH­knockdown on cell proliferation, migration, apoptosis and cell cycle arrest. Western blotting was performed to examine the protein expression levels of cell growth­ and apoptosis­associated genes. The results demonstrated that MTDH was commonly expressed in CRC cell lines. MTDH silencing significantly suppressed cell growth, colony forming ability and migration while inducing the apoptosis of HCT116 cells. In addition, MTDH depletion induced S phase cell cycle arrest in HCT116 cells. Mechanistically, knockdown of MTDH markedly downregulated the expression of phosphorylated protein kinase B, c­Myc, proliferating cell nuclear antigen and B­cell lymphoma 2 (Bcl­2) protein in HCT116 cells, and the expression of p53 and Bcl­2­associated X protein was significantly increased compared with the negative control shRNA group (P<0.05), suggesting that MTDH may function through the expression of numerous types of apoptosis­associated and signaling channel proteins in CRC cells. Taken together, these data indicated that MTDH may serve as a biomarker and candidate therapeutic target for CRC.

Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in hepatocellular carcinoma cells.

This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival. Six2 expression was higher in clinical HCC tissues than in normal tissues, and was negatively correlated with E-cadherin expression. Additionally, six2 overexpression decreased the sensitivity of HCC cells to 5-Fu, characterized as attenuating 5-FU-induced cell apoptosis and downregulation of cell viability, and promoted HCC cells stemness. Mechanistically, six2 overexpression repressed E-cadherin expression via stimulating promoter methylation of the E-cadherin. And E-cadherin overexpression rescued six2-induced decrease of 5-FU sensitivity and promotion on HCC cells stemness. Therefore, our results suggest that Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in HCC cells.

A meta-analysis of parental smoking and the risk of childhood brain tumors.

OBJECTIVE: Previous studies regarding the association between parental smoking and the risk of childhood brain tumors (CBT) have reported inconsistent results. We performed a meta-analysis to summarize evidence on this association and to quantify the potential dose-response relationship. METHODS: A systematic literature search was conducted in the Medline and Embase databases. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Dose-response meta-analysis was also performed for studies that reported categorical risk estimates for a series of smoking exposure levels. RESULTS: A total of 17 studies fulfilled the inclusion criteria. In the meta-analyses, the summary RRs (95% CIs) of CBT for maternal smoking during pregnancy, paternal smoking during pregnancy, maternal smoking before pregnancy, and paternal smoking before pregnancy were 0.96 (0.86-1.07), 1.09 (0.97-1.22), 0.93 (0.85-1.00), and 1.09 (1.00-1.20), respectively. Dose-response meta-analysis also showed no significant association between parental smoking and the risk of CBT. CONCLUSIONS: Findings from our meta-analysis indicate that parental smoking may not be associated with a risk of CBT.

Angiotensin-converting enzyme insertion/deletion gene polymorphisms and risk of intracerebral hemorrhage: a meta-analysis of epidemiologic studies.

Studies investigating the association between the intron 16 insertion/deletion (I/D) polymorphism (rs4646994) in the angiotensin-converting enzyme (ACE) gene and risk of intracerebral hemorrhage (ICH) have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. Published literature from the National Library of Medline and Embase databases were retrieved. Odds ratios (OR) and 95% confidence limits (CLs) were calculated in fixed- or random-effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included six case-control studies, which included 744 ICH cases and 1411 controls. The combined results based on all studies showed that ICH cases had a significantly lower frequency of ID genotype (OR (codominant model) = 0.43, 95% CL = 0.22, 0.84, p = 0.01). In the subgroup analysis by race, we found that ICH cases had a significantly lower frequency of II genotype in Asians (OR (recessive model) = 0.50, 95% CL = 0.38, 0.66, p < 0.001; OR (codominant model) = 0.25, 95% CL = 0.09, 0.71, p = 0.009). In conclusion, our meta-analysis suggests that ACE I/D polymorphisms are associated with ICH, especially in Asians.