Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Objective Study cisplatin intraperitoneal hot perfusion chemotherapy for colorectal cancer effect a radical cure the prognosis of the patients and the influence of immune function.Methods120 patients who underwent radical resection of colorectal cancer patients, divided into observation group and control group, 60 cases in each group.The observation group were treated with cisplatin in postoperative continuous hyperthermic perfusion chemotherapy (chemotherapy for 200mg/m2 solution to cisplatin and injected with 1L), once a week, continuous treatment three weeks.The control group was treated with mFOLFOX6 intravenous chemotherapy (oxaliplatin 100mg/m2 fluorouracil leucovorin 400mg/m2, 400mg/m2), once every two weeks, 12 times of treatment.After the treatment, observation and analysis of two groups of patients before and after treatment of tumor markers (CEA, cancer antigen 19-9, cancer antigen 242), immune function (CD3+ cells, CD4+ cells, CD8+ cells, CD4+ cell ratio/CD8+ cell natural killer cells), quality of life, and the incidence of recurrence and metastasis.ResultsAfter treatment, the quality of life of patients in the observation group the total effective rate was 91.67%, significantly higher than the control group 70.00% (P<0.05), the recurrence rate is 8.33%, the metastasis rate of 10.00% was significantly higher than the control group 28.33% and 25.00% (P<0.05).The observation group of patients with carcinoembryonic antigen, cancer antigen 19-9, cancer antigen 242 level respectively (3.4±1.1)% and (17.5±7.1)% and (4.7±1.9)% was significantly lower than the control group (10.2±2.8)% and (30.1±10.3)% and (20.3±4.5)% (P<0.05), the observation of immune function effect is improved significantly better than the control group, significant differences (P<0.05).ConclusionChemotherapy after radical resection of colorectal cancer patients using cisplatin intraperitoneal hyperthermic perfusion, can significantly reduce the recurrence rate and metastasis rate, improve immune function, reduce the level of tumor markers, so as to improve the quality of life of patients.

As an important member of metabotropic glutamate receptors (mGluR), metabotropic glutamate receptor 1 (mGluR1) plays an important role in the signal transduction of central nervous system. Selective mGluR1 antagonists can block the signaling pathway activated by mGluR1 and exert a series of physiological actions including analgesia, antianxiety, antidepression, etc. Currently, the discovery and modification of selective mGluR1 antagonists have become a hot research focus. This paper reviews the structural catalogs of selective mGluR1 antagonists and their structure-activity relationships in the last decade.

Phase separation immunoassay (PSI) combines some advantages of both homogeneous and heterogeneous immunoassays by carrying out a fast homogeneous immune reaction and a simple heterogeneous separation process. The method is readily amenable to automation. The principle of PSI is introduced. The carriers, the immobilization modes, the labels, the applications and the development of PSI are comprehensively reviewed with 60 References.