Circadian rhythms play crucial roles in orchestrating diverse physiological processes that are critical for health and disease.Dysregulated circadian rhythms are closely associated with various human metabolic diseases,including type 2 diabetes,cardiovascular disease,and non-alcoholic fatty liver disease.Modern lifestyles are frequently associated with an irregular circadian rhythm,which poses a significant risk to public health.While the central clock has a set periodicity,circadian oscillators in peripheral organs,particularly in the liver,can be entrained by metabolic alterations or stress cues.At the molecular level,the signal transduction pathways that mediate stress responses interact with the key determinants of circadian oscillation to maintain metabolic homeostasis under physiological or pathological conditions.In the liver,a number of nuclear receptors or transcriptional regulators,which are regulated by me-tabolites,hormones,the circadian clock,or environmental stressors,serve as direct links between stress responses and circadian metabolism.In this review,we summarize recent advances in the understanding of the interactions between stress responses(endoplasmic reticulum stress response,oxidative stress response,and inflammatory responses)and circadian metabolism,and the role of these interactions in the development of metabolic diseases.

Objective ToinvestigatethepatternsofbrainactivityabnormalitiesinpatientswithParkinson’sdisease(PD)with freezingofgait(FOG),andtoexploretheneuropathologicalmechanismofFOG.Methods Resting-statefunctionalMRI(rs-fMRI) scanswereobtainedfrom31PDpatientsand16healthycontrols(HCs).Accordingtothefreezingofgaitquestionnaire(FOG-Q),31 PDpatientsweredividedinto15PDFOG(+)and16PDFOG(－).ANCOVAandPost-Hocttestwereperformedtoassessinter groupdifferenceofbrainactivityabnormalitybasedonregionalhomogeneity.Results ComparedtoHCs,PDFOG(+)showeddecreased ReHointheleftinferiortemporalgyrus,rightlingual,bilateralfusiform,rightoccipitalgyrus,rightcalcarine,andrightcerebellum, whileincreasedReHointherightmiddlefrontalgyrus,rightsuperiorfrontalgyrus,rightprecentralgyrus,andrightsupplementary motorarea(SMA).ComparedtoPDFOG(－),PDFOG(+)exhibitedincreasedReHointherightprecentralgyrus,rightmiddle frontalgyrus,rightinferiorfrontalgyrus,andrightSMA,whiledecreasedReHoinleftfusiform.Conclusion Thisstudysuggests thatFOGinPDisassociatedwithabnormalitiesincerebellum,frontallobeandvisualnetwork,whichishelpfultounderstandthe neuralmechanismsunderlyingFOGinPD.

Objective To identify early Klebsiella pneumoniae(KP)infection after liver transplantation and its impact on prognosis.Methods Clinical data of 171 liver transplant recipients were retrospectively analyzed,and they were divided into the non-infection(n=52)and infection groups(n=119)according to the bacterial culture results at postoperative 2 weeks.In the infection group,KP was not detected in 86 cases(non-KP infection group),and KP was cultured in 33 cases(KP infection group).Preoperative,intraoperative and postoperative data were statistically compared between the non-infection and infection groups,and between the non-KP infection and KP infection groups.The risk factors of early KP infection after liver transplantation and the influencing factors of long-term survival of the recipients were analyzed.Results Compared with the non-infection group,model for end-stage liver disease(MELD)score and total bilirubin level were higher,the operation time was longer,the length of postoperative intensive care unit(ICU)stay and the length of hospital stay were longer,the amount of intraoperative red blood cell transfusion was higher,the hospitalization expense was higher,the incidence of severe complications was higher,white blood cell count,absolute neutrophil cell count and neutrophil-to-lymphocyte ratio at postoperative 14 and 30 d were higher,absolute lymphocyte count at postoperative 14 d was lower and hemoglobin level at postoperative 30 d was lower in the infection group.The differences were statistically significant(all P＜0.05).Compared with the non-KP infection group,MELD score,total bilirubin level and aspartate aminotransferase(AST)level were higher,the operation time and the length of postoperative ICU stay were longer,the hospitalization expense was higher,the 90-d fatality was higher,the albumin level at postoperative 14 d was lower,and total bilirubin level at postoperative 30 d was higher in the KP infection group.The differences were statistically significant(all P＜0.05).Among 33 recipients with KP infection,16 cases were resistant to carbapenem antibiotics,and 7 of them died within postoperative 90 d.Seventeen cases were intermediate or sensitive to carbapenem antibiotics,and 4 of them died within postoperative 90 d.Preoperative MELD score ≥17 and operation time≥415 min were the independent risk factors for KP infection after liver transplantation(both P＜0.05).The length of postoperative ICU stay ≥44 h and KP infection were the independent risk factors for long-term prognosis of liver transplantation(both P＜0.05).Conclusions KP infection is an independent risk factor for death after liver transplantation.High preoperative MELD score and long operation time are the independent risk factors for early KP infection after liver transplantation.