OBJECTIVES: Recent evidence suggests that the gut may be a primary site of metformin action. However, studies on the effects of metformin on gut microbiota remain limited, and its impact on gut microbial metabolites such as short-/medium-chain fatty acids is unclear. This study aims to investigate the effects of metformin on gut microbiota, short-/medium-chain fatty acids, and associated metabolic benefits in high-fat diet rats. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 3 groups: 1) Normal diet group (ND group), fed standard chow; 2) high-fat diet group (HFD group), fed a high-fat diet; 3) high-fat diet + metformin treatment group (HFD+Met group), fed a high-fat diet for 8 weeks, followed by daily intragastric administration of metformin solution (150 mg/kg body weight) starting in week 9. At the end of the experiment, all rats were sacrificed, and serum, liver, and colonic contents were collected for assessment of glucose and lipid metabolism, liver pathology, gut microbiota composition, and the concentrations of short-/medium-chain fatty acids. RESULTS: Metformin significantly improved HFD-induced glucose and lipid metabolic disorders and liver injury. Compared with the HFD group, the HFD+Met group showed reduced abundance of Blautia, Romboutsia, Bilophila, and Bacteroides, while Lactobacillus abundance significantly increased (all P<0.05). Colonic contents of butyric acid, 2-methyl butyric acid, valeric acid, octanoic acid, and lauric acid were significantly elevated (all P<0.05), whereas acetic acid, isoheptanoic acid, and nonanoic acid levels were significantly decreased (all P<0.05). Spearman correlation analysis revealed that Lactobacillus abundance was negatively correlated with body weight gain and insulin resistance, while butyrate and valerate levels were negatively correlated with insulin resistance and liver injury (all P<0.05). CONCLUSIONS Metformin significantly increases the abundance of beneficial bacteria such as Lactobacillus and promotes the production of short-/medium-chain fatty acids including butyric, valeric, and lauric acid in the colonic contents of HFD rats, suggesting that metformin may regulate host metabolism through modulation of the gut microbiota.
Animals ; Metformin/pharmacology* ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects* ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Fatty Acids, Volatile/metabolism* ; Fatty Acids/metabolism*

Inflammatory bowel disease(IBD)is a group of chronic autoimmune inflammatory disorder that attack the gastrointestinal tract,mainly categorized into two types:ulcerative colitis and Crohn′s disease.Studies have shown that the pathogenesis of IBD is complex,involving genetic,microbial,immune response,and environmental factors.Among them,the abnormal activation of the immune system,including immune cells,cytokines,and cell-to-cell interactions,as well as the alterations of the immune microenvironment,play a key role in the pathogenesis of IBD.This article reviewed the regulatory role and mechanism of immune microenvironmental changes in IBD,with the aim of providing new ideas and research direction for the formulation of immunotherapy regimens for IBD.

Inflammatory bowel disease(IBD)is a group of chronic autoimmune inflammatory disorder that attack the gastrointestinal tract,mainly categorized into two types:ulcerative colitis and Crohn′s disease.Studies have shown that the pathogenesis of IBD is complex,involving genetic,microbial,immune response,and environmental factors.Among them,the abnormal activation of the immune system,including immune cells,cytokines,and cell-to-cell interactions,as well as the alterations of the immune microenvironment,play a key role in the pathogenesis of IBD.This article reviewed the regulatory role and mechanism of immune microenvironmental changes in IBD,with the aim of providing new ideas and research direction for the formulation of immunotherapy regimens for IBD.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Objective To summarize the clinical features of patients with ovarian tumor associated anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis,and to explore the influence of operation patterns on the prognosis.Methods The clinical data of ovarian tumors with anti-NMDAR encephalitis in the Third Affiliated Hospital of Sun Yat-sen University from January 2009 to December 2018 were collected,and the clinical characteristics,treatment and prognosis were analyzed.Results A total of 110 patients with ovarian tumors and anti-NMDAR encephalitis were collected.All patients were positive for anti-NMDAR antibodies in serum and/or cerebrospinal fluid.The age of onset ranged from 10 to 35 years (24.6 ±5.7).About 60.9％ patients'initial symptom was psychosis.The main clinical features were psychosis (97.3％),seizures (83.6％),conscious disturbance (72.7％),autonomic dysfunction (64.5％),dyskinesia (64.5％),central hypoventilation (54.5％) and impaired memory (31.8％).Most patients'symptoms were relieved after surgery and immunotherapy.Postoperative pathological results revealed that ovarian teratoma accounted for 97.8％ of the ovarian tumor.The prognosis of patients with surgery was better than the patients without surgery,with statistically significant difference (P ＜ 0.05).The prognosis of patients with adnexectomy was better than the patients with ovarian tumor excision,with statistically significant difference (P ＜ 0.05).Conclusions Anti-NMDAR encephalitis,with psycho-neurological symptoms as dominant manifestation,is usually associated with ovarian tumor.For young female patients with psychosis,clinicians should be alert to the possibility of anti-NMDAR encephalitis and screen for tumor.Patients with adnexectomy and immunotherapy can get a better prognosis.

Objective To investigate the role of skin homing T lymphocytes in the development of psoriasis vulgaris(PV). Methods Indirect immunofluorescent double staining technique was employed to study the expression of infiltrating skin homing T lymphocytes in normal, uninvolved perilesional and lesional psoriatic skin in different stages (progressing, stable or regressing) and in normal human skin. Results ①Expression of cutaneous lymphocyte associated antigen (CLA) was found in the majority of CD3+T lymphocytes in normal human skin and in lesions of PV, and CD45RO phenotype was expressed in almost all CLA+T lymphocytes. ②In psoriatic lesions, the number of CD4+CLA+and CD8+CLA+cells was higher in progressive stage than that in stable stage(P