Frailty and depressive disorders exhibit a high prevalence and comorbidity rate in the elderly population.Their coexistence significantly reduces patients'quality of life,increases the risk of disability and mortality,and substantially exacerbates the socioeconomic burden.Emerging evidence indicates a significant bidirectional causal relationship between frailty and depressive disorders.The underlying comorbid mechanisms may be related to elevated levels of pro-inflammatory cytokines such as C-reactive protein,neutrophils,and white blood cells.Grey matter volume reduces in specific brain regions including the bilateral thalamus and right precentral gyrus.And abnormal hormone secretion,such as cortisol,resulting from the overactivation of the hypothalamic-pituitary-adrenal axis.Exercise interventions demonstrate positive effects in preventing and managing both frailty and depressive disorders,indicating broad application prospects.However,the underlying mechanisms require further validation.In summary,the comorbidity of frailty and depressive disorders in the elderly requires greater attention.Current evidence supports exercise intervention as an effective therapeutic strategy for improving health outcomes in this population.

Upper eyelid retraction is clinically characterized by an abnormally elevated position of the upper eyelid margin, leading to abnormal exposure of the superior sclera. Its primary etiologies include thyroid-associated orbitopathy, neurogenic causes, iatrogenic causes, trauma, and congenital developmental anomalies. This condition significantly impacts patients’ ocular function, appearance, psychological well-being, and overall quality of life. Current treatment strategies for upper eyelid retraction are generally classified into non-surgical approaches (such as pharmacologic injections or fillers) and surgical interventions. This article reviewed the research progress in the management of upper eyelid retraction aiming to provide clinicians with a reference to assist in selecting appropriate treatment plans based on the degree of retraction in individual patients, ultimately achieving functional and aesthetic rehabilitation of the upper eyelid.

AIM:This study aims to investigate the regulatory effect of the endocannabinoid 2-arachidonoyl glycerol(2-AG)on voltage-gated calcium channels(VGCCs)in caudate nucleus(CN)neurons subjected to kainic acid(KA)-induced damage,and to elucidate the underlying mechanisms involved.METHODS:Primary cultured CN neu-rons from neonatal Sprague-Dawley(SD)rats were treated with KA to establish an excitotoxic cellular model.The whole-cell patch-clamp technique was utilized to assess the effects of 2-AG on KA-induced excitotoxicity,along with the changes in the electrical properties of VGCCs.This included evaluations of current density,current-voltage relationships,and the kinetics of channel activation and inactivation.RESULTS:Treatment with KA significantly increased the current density and altered the electrical properties of VGCCs,as indicated by a reduction in the half-inactivation voltage and a shift of the inactivation curve towards depolarized potentials.Notably,KA did not affect the activation characteristics of VGCCs.Ad-ministration of exogenous 2-AG or the application of the monoacylglycerol lipase inhibitor URB602,which inhibits 2-AG degradation and elevates intracellular levels of 2-AG,effectively inhibited the KA-induced increase in VGCC current den-sity and the depolarization shift of the inactivation curve,highlighting the involvement of cannabinoid receptor 1(CB1R).CONCLUSION:The endocannabinoid 2-AG can modulate the function of VGCCs in CN neurons via the CB1R pathway,offering protective effects against excitotoxic damage induced by KA.

ObjectiveTo investigate the general situation， dietary factors， and clinical features of patients with recurrent primary common bile duct stones， and to provide a basis for effective prevention of stone recurrence. MethodsA retrospective analysis was performed for 23 730 patients who underwent cholecystectomy due to cholelithiasis in Department of Hepatobiliary， Pancreatic and Spleen Surgery， Inner Mongolia People’s Hospital， from January 2013 to December 2023， and according to the presence or absence of recurrence of primary common bile duct stones after surgery， 334 patients were divided into recurrence group. The recurrence group was further analyzed based on sex in terms of recurrence rate， recurrence cycle， recurrence age， recurrence type， and general， disease， imaging， and dietary factors. The independent-samples t test was used for comparison of continuous data between two groups， the chi-square test was used for comparison of categorical data between two groups. ResultsThere were 334 cases of recurrence of primary bile duct stones after cholecystectomy， with a recurrence rate of 1.41%， and the highest frequency of recurrence cycle was observed in 10 years after surgery， with a significant difference in recurrence cycle between the male and female patients （t=5.238， P<0.001）. There was a significant difference in the recurrence rate of stones after surgery between the patients with simple gallstones and those with gallbladder and common bile duct stones at initial diagnosis （1.23% vs 2.76%， χ²=42.104， P<0.001）. The patients with recurrence aged >60 years accounted for the highest proportion in the whole population and in both male and female populations， and 92% were Han residents； 10% of the patients with recurrence had a family history of gallstones， and as for comorbidities， the patients with hypertension accounted for the highest proportion. Among the patients with recurrence， the patients with smoking or drinking accounted for 76.7% and 10.3%， respectively. As for body weight， 63.8% of the patients with recurrence had a normal body mass index （BMI）， and 23.2% of the patients were overweight； compared with body weight at the time of the first gallbladder surgery， a reduction in body weight was observed in 60.1% of the patients with recurrence， while an increase in body weight was observed in 22.9% of the patients with recurrence. There were significant differences between the male and female patients with recurrence in age composition， ethnicity， the type of place of residence， comorbidities， smoking， drinking， BMI， and the change in body weight （all P<0.001）. As for the type of stone recurrence， the ratio of multiple stones， solitary stones， and muddy stones was 74∶15∶11， and the stone size of <1 cm， 1-2 cm， and >2 cm accounted for about 40.5%， 48.8%， and 10.6%， respectively. As for the surgical procedure， the patients undergoing laparotomy accounted for 66.1%， and those undergoing laparoscopy accounted for 33.9%. The patients with various types of dyslipidemia accounted for a percentage of<30%. There were significant differences between the male and female patients with recurrence in the type of stones at initial onset， the type and size of stones， and surgical procedure （all P<0.001）. Imaging data showed that 4 patients had an abnormal structure of the bile duct， manifesting as long and curve cystic ducts， and 73.1% of the patients had common bile duct dilatation after surgery. The follow-up of dietary factors showed irregular diets in 55.8% of the patients with recurrence. As for the dietary structure， meat and staple food accounted for 43.8% and 37.8%， respectively， which showed a sex difference， with meat in male patients and staple food in female patients； 64.1% of the patients with recurrence had a high-salt and high-oil diet； 59.8% of the patients had changes in diet after the first surgery for stones， among whom 80% were able to have a regular diet， and the patients with a regular diet accounted for 92%. ConclusionThere is a relatively low recurrence rate of primary common bile duct stones in this area， and there is no sex difference. The peak of recurrence is 10 years after surgery， and recurrence of stones is mainly observed in the population aged >60 years. The analysis of dietary and clinical features can help doctors and patients to further understand the characteristics of the recurrence of primary common bile duct stones and provide a basis for subsequent targeted prevention.

AIM:This study aims to investigate the regulatory effect of the endocannabinoid 2-arachidonoyl glycerol(2-AG)on voltage-gated calcium channels(VGCCs)in caudate nucleus(CN)neurons subjected to kainic acid(KA)-induced damage,and to elucidate the underlying mechanisms involved.METHODS:Primary cultured CN neu-rons from neonatal Sprague-Dawley(SD)rats were treated with KA to establish an excitotoxic cellular model.The whole-cell patch-clamp technique was utilized to assess the effects of 2-AG on KA-induced excitotoxicity,along with the changes in the electrical properties of VGCCs.This included evaluations of current density,current-voltage relationships,and the kinetics of channel activation and inactivation.RESULTS:Treatment with KA significantly increased the current density and altered the electrical properties of VGCCs,as indicated by a reduction in the half-inactivation voltage and a shift of the inactivation curve towards depolarized potentials.Notably,KA did not affect the activation characteristics of VGCCs.Ad-ministration of exogenous 2-AG or the application of the monoacylglycerol lipase inhibitor URB602,which inhibits 2-AG degradation and elevates intracellular levels of 2-AG,effectively inhibited the KA-induced increase in VGCC current den-sity and the depolarization shift of the inactivation curve,highlighting the involvement of cannabinoid receptor 1(CB1R).CONCLUSION:The endocannabinoid 2-AG can modulate the function of VGCCs in CN neurons via the CB1R pathway,offering protective effects against excitotoxic damage induced by KA.

Frailty and depressive disorders exhibit a high prevalence and comorbidity rate in the elderly population.Their coexistence significantly reduces patients'quality of life,increases the risk of disability and mortality,and substantially exacerbates the socioeconomic burden.Emerging evidence indicates a significant bidirectional causal relationship between frailty and depressive disorders.The underlying comorbid mechanisms may be related to elevated levels of pro-inflammatory cytokines such as C-reactive protein,neutrophils,and white blood cells.Grey matter volume reduces in specific brain regions including the bilateral thalamus and right precentral gyrus.And abnormal hormone secretion,such as cortisol,resulting from the overactivation of the hypothalamic-pituitary-adrenal axis.Exercise interventions demonstrate positive effects in preventing and managing both frailty and depressive disorders,indicating broad application prospects.However,the underlying mechanisms require further validation.In summary,the comorbidity of frailty and depressive disorders in the elderly requires greater attention.Current evidence supports exercise intervention as an effective therapeutic strategy for improving health outcomes in this population.

Upper eyelid retraction is clinically characterized by an abnormally elevated position of the upper eyelid margin, leading to abnormal exposure of the superior sclera. Its primary etiologies include thyroid-associated orbitopathy, neurogenic causes, iatrogenic causes, trauma, and congenital developmental anomalies. This condition significantly impacts patients’ ocular function, appearance, psychological well-being, and overall quality of life. Current treatment strategies for upper eyelid retraction are generally classified into non-surgical approaches (such as pharmacologic injections or fillers) and surgical interventions. This article reviewed the research progress in the management of upper eyelid retraction aiming to provide clinicians with a reference to assist in selecting appropriate treatment plans based on the degree of retraction in individual patients, ultimately achieving functional and aesthetic rehabilitation of the upper eyelid.

Objective:To explore the clinical manifestations and genetic etiology of a Chinese pedigree affected with Familial focal epilepsy with variable foci (FFEVF).Methods:A FFEVF pedigree presented at the Department of Medical Genetics of Linyi Maternal and Child Health Care Hospital on March 14, 2023 was selected as the study subject. The proband was subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of the proband and other affected members and bioinformatic analysis. This study was approved by Medical Ethics Committee of the Linyi Maternal and Child Health Care Hospital (Ethics No. QTL-YXLL-2023048).Results:WES revealed that the proband has harbored a heterozygous c. 1642C>T (p.Arg548Cys) missense variant in exon 15 of the NPRL3 gene. Sanger sequencing confirmed that the variant was inherited from the proband′s father, and multiple members of the pedigree had also harbored the same variant. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of unknown significance (PM2_supporting + PP3). Conclusion:The clinical phenotype of FFEVF patients caused by variants of NPRL3 gene is extensive, and the patients may present with neurological abnormality of autism spectrum disorder in addition to seizures.

In recent years, the carbapenem-resistant Klebsiella pneumoniae (CRKP) continues to significantly threaten public health. The limited therapeutic options are increasingly challenging for clinicians to reintroduce the polymyxin as last-resort drug, with the results that polymyxin resistance is not scarce in settings. The polymyxin resistance mechanism is diversified, mainly the modification of the lipopolysaccharide (LPS). In addition to phoPQ, pmrAB, crrAB and mgrB on chromosome, plasmid-carried mcr gene have been found to mediate the LPS modification. The mgrB gene variation plays an important role in polymyxin resistance. Above all, the aim of the current review is to discuss the mechanism of polymyxin resistance mechanism in Klebsiella pneumoniae provide insights for preventing this phenomenon.

AIM:To explore the modulation of 2-arachidonoylglycerol(2-AG)on A-type potassium channels injured by kainic acid(KA)and its molecular mechanism.METHODS:Primary cultured caudate nucleus(CN)neurons were treated with KA to establish a neuroexcitatory toxicity model.Whole-cell patch clamp recording was performed to ob-serve the changes of electrical activity of A-type potassium channels induced by KA-induced excitatory toxicity and 2-AG-mediated neuroprotective effect.RESULTS:In cultured CN neurons,patch clamp experiments confirmed that KA signifi-cantly decreased the A-type potassium channel current(IA)density and changed the electrical function of CN neurons:the slope(k)of inactivation curve and the recovery time constant(τ)after inactivation of A-type potassium channels in CN neurons were significantly increased.The experiments showed that the increase in 2-AG level,whether using 2-AG direct-ly or application of monoacylglycerol lipase inhibitor URB602 to decrease 2-AG metabolism and increase 2-AG level indi-rectly,inhibited the KA-induced reduction of IA density and the changes of electrical activity of A-type potassium channels through cannabinoid receptor 1(CB1R):2-AG effectively antagonized the KA-induced increases in τ value and k value for inactivation of A-type potassium channels,which accelerated the recovery process after inactivation of the channels.CONCLUSION:The changes of the electrical characteristics of A-type potassium channels may be one of the mecha-nisms of KA-induced excitotoxic injury of CN neurons.The 2-AG plays a neuroprotective role in KA-induced neuroexcit-atory toxic model by regulating the function of A-type potassium channels through CB1R.