Objective:To investigate the mechanism by which non-enterotoxin-producing Bacteroides fragilis (NTBF) inhibits TNF-α-induced inflammatory responses in human normal colonic epithelial cells hcoEPIC, and explore new probiotic therapies for the prevention and treatment of colitis. Methods:The co-culture system of NTBF and hcoEPIC cells was established, and the adhesion and invasion ability of NTBF were detected, respectively. TNF-α was added to induce cellular inflammation after 4 h of co-culture of NTBF and hcoEPIC cells, and cell survival and apoptosis were detected by the CCK-8 assay and the AnnexinⅤ-FITC/PI assay respectively after 24 h. Key proteins of the NF-κB signalling pathway in hcoEPIC cells in different treatment groups were detected by Western blot and RT-qPCR, and the expression of downstream cytokines of this pathway incluing IL-1β, TNF-α and IL-10 were detected by ELISA. The effect of NTBF intervention on dextran sodium sulfate(DSS)-induced colitis mice was assessed by in vivo animal experiments. Results:NTBF adhered to hcoEPIC cells, and was non-toxic to the cells. Compared with control group, NTBF treatment alone did not affect cell survival and apoptosis of hcoEPIC cells ( P>0.05), but significantly reduced cell damage and apoptosis induced by TNF-α ( P<0.05); Compared with the TNF-α treatment alone group, the expression levels of p-NF-κB p65 and p-IκBα protein as well as NF-κB and IκBα mRNA were significantly reduced ( P<0.05); the production of IL-1β and TNF-α in the cell supernatant was reduced and the release of IL-10 was increased ( P<0.05). Animal experiments demonstrated that NTBF was indeed effective in alleviating DSS-induced colitis in ulcerative colitis model mice, which was mainly manifested by inhibiting weight loss, lowering DAI scores, improving colonic shortening, and attenuating colonic pathological damage in colitis-induced mice. Conclusions:NTBF may inhibit TNF-α-induced inflammatory responses in colonic epithelial cells by down-regulating the NF-κB pathway.

Ureaplasma is a common pathogen in the human reproductive tract and consists of two distinct biotypes: biotype 1 and biotype 2. In 2002, based on the differences between biotypes, biotype 1 was further classified to a separate species named Ureaplasma parvum (Up), whereas biotype 2 is referred to as Ureaplasma urealyticum (Uu). Uu infection is associated with various urogenital diseases including infertility, preterm birth, and urethritis, while the pathogenicity of Up remains controversial. Researches have shown that different serotypes showed distinct pathogenicity and drug resistance in different diseases and populations, highlighting the importance of clinical tests of serotype and biotype for Ureaplasma. This article reviews the factors that may be associated with Ureaplasma infection, and the current status of the diagnosis and treatment in clinical practice, aiming to provide insights into the clinical significance and necessity of biotypes and serotype tests for Ureaplasma-positive cases and to serve as a reference for the clinical diagnosis and treatment of related diseases.

BACKGROUND: Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). METHODS: We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. CONCLUSION: BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors. TRIAL REGISTRAION ClinicalTrials.gov, No. NCT02226185.
Animals ; Humans ; Berberine/therapeutic use* ; Carcinogenesis ; Veillonella ; Colorectal Neoplasms/genetics* ; Tumor Microenvironment

ObjectiveTo investigate the structural features of vaginal microbiota in the early threatened abortion patients with the syndrome of kidney deficiency. MethodThirty-one patients with early threatened abortion of kidney deficiency syndrome （DK-TA group） and 116 women with normal early pregnancy （NP group） attending the First Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2018 to December 2020 were selected. The vaginal secretions were collected for 16S rRNA sequencing， which can reveal the vaginal microbiota composition and differential bacteria between the two groups. ResultThe DK-TA group had higher abundance and diversity of vaginal microbiota than the NP group. The Binary jaccard and unweighted_unifrac distance matrix analysis showed that the similarity， dispersion， abundance， and phylogenetic relationship of vaginal microbiota were significantly different between the two groups. At the phylum level， the DK-TA group had lower relative abundance of Bacteroidetes and Fusobacteria and higher relative abundance of Proteobacteria and Gemmatimonadetes than the NP group. At the genus level， the DK-TA group had lower relative abundance of Sneathia and Bifidobacterium and higher relative abundance of Escherichia-Shigella and Shuttleworthia than the NP group. Linear discriminant analysis Effect Size（LEfSe）revealed that Bacteroidetes， Fusobacteria， and Bifidobacteria were dominant in the NP group and Proteobacteria and Firmicutes in the DK-TA group. The function prediction found that DK-TA was closely associated with 38 functional pathways， including cyclic adenosine monophosphate signaling pathway and regulation of tryptophan channels by inflammatory mediators. In addition， the vaginal differential bacteria between the two groups had significant positive or negative association with the differential metabolic pathways. ConclusionProteobacteria， Gemmatimonadetes， and Bacteroidetes in the vaginal microbiota may be biomarkers for threatened abortion of kidney deficiency syndrome.

Metformin is one of the commonly used hypoglycemic drugs in clinical practice. In addition to hypoglycemia, there are a variety of medical biological values that have been constantly discovered and attracted much attention. In recent years, studies have shown that metformin through activation of AMPK inhibition of sterols regulating element binding protein 1 (SREBP-1) reduce lipid synthesis, in the treatment of liver steatosis, improve insulin sensitivity, prevention Metformin is one of the commonly used hypoglycemic drugs in clinical practice. In addition to hypoglycemia, there are a variety of medical biological values that have been constantly discovered and attracted much attention. In recent years, studies have shown that metformin through activation of AMPK inhibition of sterols regulating element binding protein 1 (SREBP-1) reduce lipid synthesis, in the treatment of liver steatosis, improve insulin sensitivity, prevention of atherosclerosis and cardiovascular dysfunction, tumor, polycystic ovary syndrome and adjuvant therapy of COVID-19 aspects play a role. Therefore, this article reviews the possible mechanism and clinical application of metformin in regulating glucose and lipid metabolism by inhibiting SREBP-1 through activating AMPK.

Objective:To evaluate the effects of single spay of L-menthol (NPO-11) on suppressing gastric peristalsis during upper gastrointestinal endoscopy and the influencing factor.Methods:This study was a multicenter, randomized, double-blind, placebo-parallel controlled study. The eligible patients were randomly divided into two groups by randomized blocks. Patients received local spray of either NPO-11 (160 mg L-menthol) or placebo 20 mL during upper gastrointestinal endoscopy. The gastric peristalsis was recorded and evaluated before, 2 minutes after and at the end of endoscopy. The complexity of the procedure was evaluated by the researchers. The influencing factors for antiperistaltic effect of NPO-11 were analyzed.Results:A total of 220 patients were enrolled from five research centers. There were 109 cases in the NPO-11 group and 111 cases in the placebo group. The baseline data of the two groups were similar and comparable. The proportion of patients with grade 1 peristalsis at 2 minutes after the treatment and at the end of endoscopy was significantly higher in the NPO-11 group than that in the placebo group [40.37% (44/109) VS 16.22% (18/111), χ2=15.93, P<0.001]. Compared with the placebo group, the proportions of weak peristalsis (grade 1 and 2) were higher in the NPO-11 group at 2 minutes after the treatment [67.89% (74/109) VS 46.85% (52/111)] and at the end of endoscopy [79.82% (87/109) VS 48.65% (54/111)]. Subgroup analysis showed that the inhibitory effect of NPO-11 on gastric peristalsis was more significant in Helicobacter pylori antibody positive group. Conclusion:Local spray of NPO-11 can effectively inhibit gastric peristalsis during upper gastrointestinal endoscopy, and its effect is more significant in Helicobacter pylori antibody positive group. It could be recommended for no obvious adverse reactions , its safety, and the convenient procedure.

The incidence and mortality of early-onset colorectal cancer (EOCRC) are increasing worldwide and have become a major issue in the field of public health. Dietary, environment and lifestyle factors are related to the incidence of EOCRC, and gut microbiota may play an important role in the development of EOCRC. This article reviewed the risk factors of EOCRC, the potential relationship between gut microbiota and EOCRC, and the prevention of EOCRC, which may provide new ideas for the prevention and treatment of EOCRC.

Lung cancer is one of the malignant tumors with serious health consequences for people all over the world.Non small-cell lung cancer(NSCLC)is the most common type of lung cancer,making up 80％ to 85％ of all cases.As a result of low rates of early detection,more than 70％ of patients,many of them elderly patients,are in late stages(Ⅲ-Ⅳ)at the time of diagnosis,and cannot be effectively treated with surgery.First line chemotherapy is the most common and critical treatment for patients with advanced or recurrent lung cancer.Elderly patients show decreased tolerance for side effects and toxicities of chemotherapy agents because of low basic metabolic rates and functional decline of major organs.Therefore,first-line chemotherapy strategies for elderly patients with NSCLC need further investigation.

Educational reform of pathophysiology oriented to clinical application is to pass the physician qualifica -tion examination .One of essential approach is to implement pathophysiology teaching with the translational medical philosophy and promote the harmonious development of physician -patient relationship with the utilization of the de-velopment and changes of disease in the teaching process .In that way, the pathophysiology in basic and clinical medicine is worthy of the name of “bridge”, and ultimately achieves the goal of “the transformation and develop-ment of the cultivation of clinical application talents”.

Objective To investigate the relationship between genetic variants in the Toll-like receptor (TLR) pathway genes and susceptibility of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC).Methods The data of whole genome association studies of the high-risk population of GC and ESCC in China were analyzed by adaptive rank-truncated product (ARTP) method in pathway and gene level.The associations between single nucleotide polymorphism (SNP) and susceptibility of GC and ESCC were analyzed with additive model of unconditional Logistic regressions.PLINK 1.07 and SPSS 19.0 software were performed for statistical analyses,and ARTP package in R3.0.2 was used for pathway and gene level analysis.Results In gene-level analyses,eight genes were found to be associated with susceptibility of GC (P ＜0.05) and six genes were associated with susceptibility of ESCC (P ＜ 0.05).In single SNP-level analyses,21 SNPs were statistically correlated with susceptibility of GC (P ＜ 0.01),and 11 SNPs were statistically correlated with susceptibility of ESCC (P ＜0.01).Conclusions Some genetic variants in TLR pathway are associated with risk of GC and ESCC.The potential molecular mechanisms need further investigation.