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.

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.

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.

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.