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.

BACKGROUND:Resveratrol is a natural antioxidant extracted from plants.Its mechanism of improving exercise-induced fatigue mainly focuses on the protective effect against oxidative stress and inflammation.In this study,the protective mechanism of resveratrol on exercise-induced fatigue was mainly discussed from the perspective of gluconeogenesis. OBJECTIVE:To investigate the effect of resveratrol on gluconeogenesis in exercise-induced fatigue rats. METHODS:After 1 week of adaptive training,male Sprague-Dawley rats were randomly divided into 4 groups with 12 rats in each group:blank control group,resveratrol group,exercise group,resveratrol + exercise group.Weight-bearing swimming training was used to simulate long-term medium-high intensity exercise.After swimming with a weight of 5%for 1 hour every day,50 mg/kg resveratrol solution or the same volume of dimethyl sulfoxide solvent were given orally,6 days a week,for a total of 6 weeks.Samples were collected 24 hours after the last exercise,and the levels of urea nitrogen,creatine kinase,blood glucose,liver glycogen and lactic acid and pyruvate in liver tissue were detected by the kit.The activity of phosphoenolpyruvate carboxykinase was detected by microassay,and the activity of glucose-6-phosphatase was detected by enzyme-linked immunosorbent assay.Real-time fluorescence quantitative PCR was used to detect the gene expression of silent information regulator 1,cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α. RESULTS AND CONCLUSION:In the exercise group,plasma urea nitrogen and creatine kinase levels of rats were significantly increased(both P<0.05),liver lactate and pyruvate levels and lactate/pyruvate ratio were significantly increased(all P<0.01),and blood glucose and liver glycogen contents were significantly decreased(both P<0.01).Resveratrol supplementation could effectively improve the above conditions.Exercise significantly decreased the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase(P<0.01,P<0.05),and resveratrol supplementation significantly increased the activity of phosphoenolpyruvate carboxykinase in liver tissue(P<0.01).The mRNA expression levels of silent information regulator 1,cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α in liver tissue of the exercise group were significantly decreased(all P<0.01),while resveratrol supplementation could significantly increase the gene expression levels of this pathway.To conclude,resveratrol can relieve exercise-induced fatigue caused by long-term medium-high intensity exercise,and its mechanism may be related to up-regulating the gluconeogenesis regulatory pathway,improving rate-limiting enzyme activity,promoting liver gluconeogenesis,and increasing blood glucose and liver glycogen levels.

BACKGROUND:Studies have shown that resveratrol can relieve exercise-induced fatigue and protect the heart,but its action mechanism needs further study. OBJECTIVE:To explore the protective effect and regulatory mechanism of resveratrol on ventricular remodeling in exercise-induced fatigue rats. METHODS:Totally 48 male Sprague-Dawley rats were randomly divided into four groups,with 12 rats in each group.Rats in the blank control group were fed conventionally.After one week of adaptive training,rats in the exercise-related fatigue group and exercise-related fatigue with resveratrol supplement group were trained by 6-week weight-bearing swimming(5%body mass lead block fixed in the tail,70%-80%maximal oxygen uptake intensity),6 days a week,60 minutes a day.Rats in the resveratrol supplement group and exercise-related fatigue with resveratrol supplement group were given resveratrol(50 mg/kg per day)by gavage one hour after exercise intervention.Blank control group and exercise-related fatigue group were given the same volume of 2%dimethyl sulfoxide,6 days a week,once a day for 6 weeks.The body mass and heart mass of the rats were measured 24 hours after the last intervention.Plasma creatine kinase isoenzyme,cardiac troponin 1,pyruvate dehydrogenase and uncoupling protein 1 levels in myocardial tissue were determined by ELISA.The mRNA expression levels of ventricular remodeling-related factor Foxp1,transforming growth factor β1 and endothelin 1 were detected by RT-PCR. RESULTS AND CONCLUSION:Compared with the blank control group,the body mass of rats decreased and the heart mass increased in the exercise-related fatigue group(P＜0.05).Compared with the exercise-related fatigue group,the body mass and heart mass of the rats reduced in the exercise-related fatigue with resveratrol supplement group(P＜0.05).Compared with the blank control group,the levels of creatine kinase isoenzyme,cardiac troponin 1 and uncoupling protein 1 increased(P＜0.01),and the level of pyruvate dehydrogenase decreased(P＜0.01)in the exercise-related fatigue group.Compared with the exercise-related fatigue group,the levels of creatine kinase isoenzyme,myocardial troponin 1 and uncoupling protein 1 decreased(P＜0.05),and the level of pyruvate dehydrogenase increased(P＜0.05)in the exercise-related fatigue with resveratrol supplement group.Compared with the blank control group,the expression of the Foxp1 gene decreased(P＜0.01),and the expression of transforming growth factor β1 and endothelin 1 gene increased(P＜0.01)in the myocardium of the exercise-related fatigue group.Compared with the exercise-related fatigue group,the expression of the Foxp1 gene in the myocardium of the exercise-related fatigue with resveratrol supplement group increased(P＜0.01),while the expression of the transforming growth factor β1 and endothelin 1 gene decreased(P＜0.05).It is suggested that exercise-induced fatigue can promote myocardial adaptability and cause compensatory hypertrophy.Resveratrol can improve myocardial injury and energy metabolism and delay ventricular energy remodeling in rats.This effect may be related to the regulation of Foxp1/transforming growth factor β1/endothelin 1 signaling pathway.

ObjectiveTo understand the current drug resistance status and bacterial multilocus sequence typing （MLST） of human and avian Campylobacter jejuni in Jinshan District， Shanghai. MethodsFecal samples were collected from diarrhea patients in the annuity mountainous area from 2021 to 2022， and poultry and related samples were collected from 2 poultry farms in the Jinshan area for detection of C. jejuni. Minimal inhibitory concentration （MIC） drug sensitivity test was performed on the detected C. jejuni， and some strains were selected for whole genome sequencing and MLST analysis. ResultsA total of 823 samples of diarrhea disease were collected， and 32 strains of C. jejuni were detected， with a detection rate of 3.89%. Out of 600 poultry related samples， 62 strains of C. jejuni were detected， with a detection rate of 10.33%. Human multidrug resistance reached 93.75% （30/32）， while avian multidrug resistance reached 100.00%（62/62）. The top four drug resistance rates of human and avian C. jejuni were azithromycin （100.00% from humans and 100.00% from birds）， naphthoic acid （93.75% from humans and 87.10% from birds）， ciprofloxacin （90.63% from humans and 98.39% from birds）， and tetracycline （84.38% from humans and 98.39% from birds）. The relatively low resistance strains of human derived C. were erythromycin， chloramphenicol， and thalithromycin. The relatively low resistance strains of avian C. jejuni were erythromycin， clindamycin， and flufenicol. MLST analysis showed that the selected 16 strains of bacteria were divided into 9 ST types， among which the evolutionary relationship of avian C. jejuni was relatively concentrated， while human C. jejuni was relatively dispersed. It was found that one strain of avian C. jejuni was closely related to two strains of human C. jejuni. ConclusionsC. jejuni infection is severe in patients with diarrhea in this region， with a detection rate second only to salmonella and Vibrio parahaemolyticus. C. jejuni infection in poultry is relatively common， and both are highly resistant. Therefore， monitoring and control should be strengthened. MLST analysis shows new ST types in both avian and human sources of C. jejuni， indicating the emergence of new mutations that require continuous monitoring to avoid the epidemics caused by new strains. The isolated strains with close genetic relationships between avian and human sources reveal the evidence of the spread of C. jejuni from poultry to humans. Therefore it is necessary to strengthen the monitoring of C. jejuni in relevant samples from breeding farms.

The genus jujube(Ziziphus jujuba Mill.)within the Rhamnaceae family encompasses numerous varieties,such as Ziziphus jujuba Mill.var.jujuba,Ziziphus jujuba var.inermis,and var.spinosa,etc.Among these,the jujube fructus has the most abundant cultivated variants across the country,including Ziziphus jujuba cv.Hamidazao and Ziziphus jujuba cv.Huanghetanzao.Jujube plants are rich in variety and are used for both medicinal and food purposes.Polysaccharides,one of the main active ingredients of jujube,are important medicinal components that contribute to its efficacy.Jujube polysaccharides have been found to promote hematopoiesis,exhibit antioxidant and anti-tumor activities,repair liver damage,regulate the immune system,and provide anti-inflammatory effects.By comprehensively summarizing and analyzing the literature on jujube polysaccharides from different varieties and origins,this paper reviews the potential mechanisms of action of jujube polysaccharides in exerting biological activities.It also summarizes the primary structural features,such as relative molecular mass,monosaccharide composition,glycosidic linkage,and the substituent modifications of jujube polysaccharides by sulfation,phosphorylation,carboxymethylation,selenization,and acetylation.This review aims to provide a reference for the research and development of jujube in the fields of innovative polysaccharide drugs and functional foods.

In recent years,enhanced recovery after surgery(ERAS)has been widely used in clinical practice,aiming to optimize perioperative management measures through evidence-based medicine and reduce the physical and mental trauma,stress reactions,and complications of surgical patients through multidisciplinary collaboration.This paper examined the clinical practice of ERAS from the perspective of medical humanities,reviewed its development and characteristics,and first pointed out that the concept of"minimal harm"laid the medical humanities foundation for ERAS.However,the concept of"minimum harm"faced ethical and realistic challenges in practice,such as differentiated cognition between benefits and non-harm,the tension between generalization and personalization,and the gap between rehabilitation continuity and family care.This paper led into the caregiving perspective of social sciences,proposed"optimal care"as a supplement to the medical humanities concept of ERAS,and introduced its connotation and practice.The combination of"minimal harm"and"optimal care"can provide theoretical guidance for medical humanistic care in ERAS and innovate the practical path of medical humanities into clinical practice.

In recent years,enhanced recovery after surgery(ERAS)has been widely used in clinical practice,aiming to optimize perioperative management measures through evidence-based medicine and reduce the physical and mental trauma,stress reactions,and complications of surgical patients through multidisciplinary collaboration.This paper examined the clinical practice of ERAS from the perspective of medical humanities,reviewed its development and characteristics,and first pointed out that the concept of"minimal harm"laid the medical humanities foundation for ERAS.However,the concept of"minimum harm"faced ethical and realistic challenges in practice,such as differentiated cognition between benefits and non-harm,the tension between generalization and personalization,and the gap between rehabilitation continuity and family care.This paper led into the caregiving perspective of social sciences,proposed"optimal care"as a supplement to the medical humanities concept of ERAS,and introduced its connotation and practice.The combination of"minimal harm"and"optimal care"can provide theoretical guidance for medical humanistic care in ERAS and innovate the practical path of medical humanities into clinical practice.

In recent years,enhanced recovery after surgery(ERAS)has been widely used in clinical practice,aiming to optimize perioperative management measures through evidence-based medicine and reduce the physical and mental trauma,stress reactions,and complications of surgical patients through multidisciplinary collaboration.This paper examined the clinical practice of ERAS from the perspective of medical humanities,reviewed its development and characteristics,and first pointed out that the concept of"minimal harm"laid the medical humanities foundation for ERAS.However,the concept of"minimum harm"faced ethical and realistic challenges in practice,such as differentiated cognition between benefits and non-harm,the tension between generalization and personalization,and the gap between rehabilitation continuity and family care.This paper led into the caregiving perspective of social sciences,proposed"optimal care"as a supplement to the medical humanities concept of ERAS,and introduced its connotation and practice.The combination of"minimal harm"and"optimal care"can provide theoretical guidance for medical humanistic care in ERAS and innovate the practical path of medical humanities into clinical practice.

In recent years,enhanced recovery after surgery(ERAS)has been widely used in clinical practice,aiming to optimize perioperative management measures through evidence-based medicine and reduce the physical and mental trauma,stress reactions,and complications of surgical patients through multidisciplinary collaboration.This paper examined the clinical practice of ERAS from the perspective of medical humanities,reviewed its development and characteristics,and first pointed out that the concept of"minimal harm"laid the medical humanities foundation for ERAS.However,the concept of"minimum harm"faced ethical and realistic challenges in practice,such as differentiated cognition between benefits and non-harm,the tension between generalization and personalization,and the gap between rehabilitation continuity and family care.This paper led into the caregiving perspective of social sciences,proposed"optimal care"as a supplement to the medical humanities concept of ERAS,and introduced its connotation and practice.The combination of"minimal harm"and"optimal care"can provide theoretical guidance for medical humanistic care in ERAS and innovate the practical path of medical humanities into clinical practice.

In recent years,enhanced recovery after surgery(ERAS)has been widely used in clinical practice,aiming to optimize perioperative management measures through evidence-based medicine and reduce the physical and mental trauma,stress reactions,and complications of surgical patients through multidisciplinary collaboration.This paper examined the clinical practice of ERAS from the perspective of medical humanities,reviewed its development and characteristics,and first pointed out that the concept of"minimal harm"laid the medical humanities foundation for ERAS.However,the concept of"minimum harm"faced ethical and realistic challenges in practice,such as differentiated cognition between benefits and non-harm,the tension between generalization and personalization,and the gap between rehabilitation continuity and family care.This paper led into the caregiving perspective of social sciences,proposed"optimal care"as a supplement to the medical humanities concept of ERAS,and introduced its connotation and practice.The combination of"minimal harm"and"optimal care"can provide theoretical guidance for medical humanistic care in ERAS and innovate the practical path of medical humanities into clinical practice.