No abstract

Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases that can breakdown almost all extracellular matrix components. MMP8 and MMP9 have been shown to be associated with breast cancer (BC) risk in European and American populations. However, few studies have focused on the polymorphisms of MMP8 and MMP9 in Chinese Han BC patients. We investigated nine single nucleotide polymorphisms (SNPs) in 571 BC cases and 578 controls to evaluating their association with risk of BC. The frequency of the “A” allele of rs3787268 was significantly lower in BC cases than in controls (P = 0.025). In the genetic model analysis, the minor allele “T” of rs11225394 in MMP8 was associated with increased risk of BC under the recessive model (P = 0.019), and the minor allele “A” of rs3787268 was associated with decreased risk of BC under the dominant model (P = 0.014). Additionally, the haplotype “AGTCA” constructed by rs3740938, rs2012390, rs1940475, rs11225394, and rs11225395 and the haplotype “CCG” constructed by rs3918249, rs3918254 and rs3787268 were associated with increased risk of BC (P < 0.05). Our data showed that polymorphisms of MMP8 and MMP9 may be associated with BC risk in the Chinese Han population.

Over the past two decades, it is improved gut microbiota plays an important role in the health and disease pathogenesis. Metabolites, small molecules produced as intermediate or end products of microbial metabolism, is considered as one of the major interaction way for gut microbiota with the host. Bacterial metabolisms of dietary substrates, modification of host molecules or bacteria are the major source of metabolites. Signals from microbial metabolites affect immune maturation and homeostasis, host energy metabolism as well as mucosal integrity maintenance. Based on many researches, the composition and function of the microbiota can be changed, which is also seen in the metabolite profiles of patients with inflammatory bowel disease (IBD). Additionally, some specific classes of metabolites also can trigger IBD. In this paper, definition of the key classes of microbial-derived metabolites which are changed in IBD, description of the pathophysiological basis of association and identification of the precision therapeutic modulation in the future are the major contents.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by a relapsing-remitting course owing to recurrent intestinal inflammation. UC often has symptoms such as intermittent rectal bleeding, diarrhea, and abdominal pain. As the precise etiology of UC has not completely clarified, UC has become a public health challenge worldwide. According to an epidemiological survey, there were about 350,000 new cases of IBD in China from 2005 to 2014. By 2025, the number of IBD patients in China will reach 1.5 million. Traditional Chinese medicine (TCM) has been widely used to treat UC in China, however, it is still challenging to systematically determine the efficacy of in UC. Therefore, this trial aims to evaluate the clinical efficacy and safety of CHM in the treatment of mild active UC patients. Methods: A multi-center, double-blinding, double-dummy, active-controlled, randomized trial will be established. A total of 240 patients in 6 centers with mild active UC (Mayo score is 3–5 points) and TCM syndrome of damp-heat stasis blocking and spleen-qi deficiency will be randomly allocated in the ratio of 1:1 to 2 groups: the experimental group and the control group. The experimental group will receive Hudi enteric-coated capsules (HEC) and enteric-coated mesalazine tablets placebo; the control group will receive enteric-coated mesalazine tablets and HEC placebo. Each group will be treated for 8 weeks. The primary therapeutic outcome: the rate of clinical efficacy and clinical remission at 8 weeks of treatment (last survey point) according to the modified Mayo score. The secondary outcomes: individual symptom score, TCM syndrome score, endoscopic response rate, mucosal healing rate, and quality of life scale score. Outcomes will be assessed at baseline and the end of the trial. Besides, intestinal mucosa, stools and blood biopsies from the mild active UC patients before and after treatment will be collected to reveal the underlying mechanisms. Discussion: The results of this trial will provide compelling evidence of the efficacy and safety of HEC for treatment of mild active UC and preliminarily show the potential mechanism of how HEC acts. Finally, it will widen treatment options for patients with mild active UC.

With the development of microbiology and metabolomics, the relationship between the intestinal microbiome and intestinal diseases has been revealed. Fecal microbiota transplantation (FMT), as a new treatment method, can affect the course of many chronic diseases such as metabolic syndrome, malignant tumor, autoimmune disease and nervous system disease. Although the mechanism of action of FMT is now well understood, there is some controversy in metabolic diseases, so its clinical application may be limited. Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection, and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases. However, the initial results are varied, suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT. The success of FMT depends on the microbial diversity and composition of donor feces. Therefore, clinical trials may fail due to the selection of ineffective donors, and not to faulty indication selection for FMT. A new understanding is that FMT not only improves insulin sensitivity, but may also alter the natural course of type 1 diabetes by modulating autoimmunity. In this review, we focus on the main mechanisms and deficiencies of FMT, and explore the optimal design of FMT research, especially in the field of cardiometabolic diseases.