Objective To comprehensively evaluate the causal relationship between gut microbiota and 9 respiratory diseases, explore whether there are common mechanisms among these 9 respiratory diseases, and delves into the potential commonalities of pre-chronic obstructive pulmonary disease (pre-COPD) by focusing on COPD, emphysema, and chronic bronchitis. Methods Mendelian randomization was used to explore the causal relationship between gut microbiota and 9 respiratory diseases, sensitivity analysis was conducted, and robustness was verified. Single nucleotide polymorphisms of common gut microbiota were mapped to genes to explore their common mechanisms. Results Mendelian randomization studies found that 66 gut microbiota had a causal relationship with 9 respiratory diseases, and 15 gut microbiota might be potential common mechanisms for these 9 respiratory diseases, with a total of 85 potential genes. GO functional enrichment analysis found that these genes were mainly enriched in biological functions such as synaptic transmission, synaptic membrane, cytokine activity, and growth factor binding. KEGG enrichment analysis showed that these genes were mainly enriched in glutamatergic synapses, relaxin signaling pathway, calcium signaling pathway, Rap1 signaling pathway, and PI3K-Akt signaling pathway. Allisonella and Prevotellaceae might be protective factors for pre-COPD, while Howardella might be a risk factor. Ten protective genes and six risk genes for the pre-COPD were identified. Conclusion This study further confirms the correlation between the lung-gut axis and the lung-colon connection, explores the potential common mechanisms of 9 respiratory diseases, investigates the potential mechanisms of pre-COPD based on the common gut microbiota of COPD, chronic bronchitis, and emphysema, and provides some ideas for the early prevention and treatment of COPD, and diagnosis of pre-COPD from the perspective of gut microbiota.

Non-typhoid Salmonella(NTS)is widely distributed around the world, mainly infected children under 5 years of age.Salmonella Enteritidis and Salmonella Typhimurium are the main serotypes.NTS are major cause of acute gastroenteritis, but the invasive diseases such as bacteremia and meningitis are more serious.The antibiotic resis-tance of NTS is severe, and irrational use of antibiotics is ubiquitous.Now, the epidemiology, clinical characteristics, susceptible factor and antibiotic therapy of NTS infection in children were summarized, which helps early diagnose and rational antibiotic therapy.

Objective To investigate the effects and mechanisms of shRNA interfered with expression of leucine-rich repeat containing G-protein coupled receptor 5 (Lgr5) on the malignant behaviors of colorectal cancer stem cells (CSCs).Methods The experimental study was conducted.The CSCs expressing Lgr5+ were sorted by fluorescence activated cell sorting.Lgr5+ cells that were transfected with Lgr5-shRNA lentiviral vector and nontarget shRNA lentiviral vector were respectively allocated into the experimental group and control group.The percentage of Lgr5+ cells was analyzed by flow cytometery.The relative expression of Lgr5 mRNA was detected by fluorescence quantitative real-time polymerase chain reaction (qRT-PCR).The capacity of self-renewal was detected by sphere forming assay.The tumorigenesis in vitro and in vivo were respectively measured by colony formation assay and xenografting experiment.The mRNA expressions of stem cells related genes (Oct4,Sox2,Nanog,KLF4),CSCs genes (CD133,CD44,ALDH) and Wnt/β-catenin pathway key genes (Axin2,Wnt5a,Wnt3a,Fzd3,c-myc,VEGF,Ascl2,claudin-1) were detected by qRT-PCR.Measurement data with normal distribution were represented as-x±s.Comparison between groups was analyzed using the t test.Results (1)Transfection efficiency of shRNA lentiviral vector induced Lgr5 by flow cytometery was respectively 6.8％± 1.0％ in the experimental group and 92.7％±3.3％ in the control group,with a statistically significant difference (t =43.148,P＜0.05).The relative expression of Lgr5 mRNA measured by qPT-PCR was respectively 0.168±0.057 in the experimental group and 1.148±0.004 in the control group,with a statistically significant difference (t=28.778,P＜0.05).(2) The capacity of self-renewal was detected by sphere forming assay.The results of sphere forming assay:the number of spheres was 29±6 in the experimental group and 410± 10 in the control group,with a statistically significant difference (t =41.070,P＜0.05).The results of colony formation assay:the numbers of colonies in the experimental group and control group were respectively 72±4 and 412± 19,showing a statistically significant difference (t =31.433,P＜ 0.05).The results of tumorigenesis:the volumes of tumors in the experimental group and control group were respectively (81± 15)mm3 and (328±24)mm3,with a statistically significant difference (t=11.304,P＜0.05).(3) The effects of Lgr5 down-regulation on related genes,results of qRT-PCR detection:① The mRNA relative expressions of Oct4,Sox2,Nanog and KLF4 (stem cells related genes) were 0.377±0.093,0.662±0.104,3.591±0.300,0.425±0.091 in the experimental group and 1.957± 0.026,2.137±0.015,5.831±0.165,1.536±0.014 in the control group,with statistically significant differences (t=23.079,22.261,8.446,19.186,P＜0.05).② The mRNA relative expressions of CD133,CD44 and ALDH (CSCs genes) were 1.490±0.155,5.535±0.487,1.640±0.039 in the experimental group and 2.488± 0.061,9.908±0.332,5.718±0.292 in the control group,with statistically significant differences (t =8.170,9.667,27.849,P＜0.05).③The mRNA relative expressions of Axin2,Wnt5a,Wnt3a,Fzd3,c-myc,VEGF,Ascl2 and claudin-1 genes in the Wnt/β-catenin pathway were respectively 1.592±0.267,0.528±0.138,2.153±0.078,1.480±0.064,0.248±0.128,1.492±0.025,0.658±0.095,1.647±0.087 in the experimental group and 3.651±0.224,2.570±0.093,2.301±0.157,1.636±0.058,1.415±0.080,2.610±0.159,2.480±0.123,3.432±0.273 in the control group.There were statistically significant differences in the mRNA relative expressions of Axin2,Wnt5a,c-myc,VEGF,Ascl2 and claudin-1 genes between the 2 groups (t =7.316,15.332,12.649,12.320,14.831,9.063,P＜0.05),and no statistically significant difference in the mRNA relative expressions of Wnt3a and Fzd3 between the 2 groups (t =2.887,2.242,P＞0.05).Conclusion The malignant behaviors of colorectal CSCs are suppressed after shRNA lentivirus interfered with expression of Lrg5,and its mechanism is related to inhibiting activity of Wnt/β-catenin pathway.