ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

OBJECTIVE To conduct a comprehensive clinical evaluation of four nucleoside （acid） analogues that have been approved and marketed in China， such as entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide fumarate， and tenofovir amibufenamide. METHODS According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs （2021 edition， trial implementation）， a comprehensive search was conducted across databases including CNKI， Wanfang Data， VIP， PubMed， the Cochrane Library， Embase， as well as relevant official websites. Drug package inserts， guidelines， consensus statements， and relevant literature for the four drugs were collected and subjected to a comprehensive evaluation across six dimensions： safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility. RESULTS The scores for entecavir in terms of safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility-along with its comprehensive score-were 13， 14， 13， 10， 18， and 6， totaling 74 points. For tenofovir disoproxil fumarate， the respective scores were 13， 17， 18， 8， 18， and 7， totaling 81 points. For tenofovir alafenamide fumarate， the scores were 14， 20， 12， 8， 18， and 5， totaling 77 points. Finally， for tenofovir amibufenamide， the scores were 10.5， 17， 10， 6， 15， and 4， totaling 62.5 points. CONCLUSIONS Tenofovir disoproxil fumarate， with the highest score， is recommended as the first-line option， suitable for adults， children， and pregnant women. However， caution is warranted for potential renal impairment. Tenofovir alafenamide fumarate is recommended as a second-line alternative， particularly for individuals at high risk for bone and renal damage. Entecavir has a score similar to tenofovir alafenamide fumarate but requires dosing on an empty stomach and dose adjustment based on renal function of patients. Tenofovir amibufenamide received the lowest score and is considered a weak recommendation. The clinical application of these nucleoside （acid） analogues should be individualized based on the patient’s age， physiological status， and risk factors.

Objective To develop a reminiscence therapy program with Montessori educational philosophy in treatment of elderly people with mild cognitive impairment(MCI)in nursing homes and evaluate its effect.Methods On the basis of Montessori education principles,a reminiscence therapy program was drafted through literature review and had it finalised with expert consultations and a pilot study.Between February and May 2022,70 elderly with MCI were recruited from a nursing home in Liaoning Province using convenience sampling.The recruited elderly were randomly divided into a control group(n=35)and an intervention group(n=35)using a random number table.The elderly in control group received conventional cognitive training only while the elderly in the intervention group received reminiscence therapy in addition to the conventional cognitive training.Cognitive function and ability of daily living(ADL)were compared between the two groups after a 6-week intervention.Results The elderly in intervention group demonstrated statistically significant improvements in both cognitive function and dimensions(visuospatial/executive function,naming ability,delayed recall and orientation,as well as in ADL after a 6-week intervention(all P<0.05).Conclusion The Montessori philosophy based on reminiscence therapy improves cognitive function and activities of daily living in the elderly with MCI,particularly from the perspectives of visuospatial/executive function,naming ability,delayed recall and orientation.

Objective:To investigate effect and mechanism of hydroxysafflor yellow A(HSYA)activating neuronal autophagy on cerebral ischemia-reperfusion injury through a combination of in vitro and in vivo experiments.Methods:SD rat MCAO/R model was established by improved suture method.Rats were randomly divided into sham surgery(Sham)group,MCAO/R group and MCAO/R+HSYA group,following indicators were detected to determine extent of cerebral ischemia-reperfusion nerve damage:Z-Longa neu-rological function score was detected,TTC staining to measure cerebral infarction area,and TUNEL staining to measure cell apopto-sis;Western blot was used to detect protein expressions of autophagy related markers LC3,Beclin1,P62 and SIRT1 in rat brain tis-sue;immunofluorescence staining was used to observe expression of LC3 co-localization with neurons.OGD/R injury model of SH-SY5Y cells was established and randomly divided into Normal group,OGD/R group,OGD/R+HSYA group,OGD/R+SIRT1 inhibitor(EX-527)group and OGD/R+EX-527+HSYA group.Western blot was used to detect protein expressions of LC3,Beclin1,P62 and SIRT1.Results:Compared with Sham group,model group rats showed impaired neurological function,significantly increased neu-robehavioral scores,widespread cerebral infarction,significantly increased neuronal cell apoptosis,significantly increased autophagy related protein Beclin1 expression and LC3-Ⅱ/LC3-Ⅰ,significantly decreased P62 expression,significantly increased LC3/NeuN co-stained cells,and decreased SIRT1 expression;compared with model group,HSYA intervention group showed a significant decrease in neurological functional scores,a significant reduction in cerebral infarction area,a significant decrease in neuronal cell apoptosis,a further increase in Beclin1 expression and LC3-Ⅱ/LC3-Ⅰ,a further decrease in P62 expression,number of LC3/NeuN and P62/NeuN co-stained cells also increased,and SIRT1 expression significantly increased.Expression trends of Beclin1,LC3-Ⅱ/LC3-Ⅰ,P62 and SIRT1 of cells between normal group,model group and HSYA intervention group were same as animal experiment;compared with model group,expressions of SIRT1,Beclin1 and LC3-Ⅱ/LC3-Ⅰ in OGD/R+EX-527 group were significantly reduced,while expression of P62 was significantly increased;compared with OGD/R+EX-527 group,there was no significant change in SIRT1 expression in OGD/R+EX-527+HSYA group,LC3-Ⅱ/LC3-Ⅰ and Beclin1 expression were significantly increased,and P62 expres-sion was significantly decreased.Conclusion:HSYA can significantly improve neurological deficits in rats after cerebral ischemia-reperfusion,reduce cerebral infarction area,and decrease neuronal cell apoptosis rate,whose neuroprotective effect may be related to its activation of SIRT1,which significantly enhances neuronal autophagy.

Poliovirus receptor(PVR)family includes several immune checkpoint receptors such as T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif structural domains(TIGIT),CD96 and CD226,and their ligands CD155 and CD112,etc.PVR family members have sequence homology and highly interact with each other for synergistic stimulatory or inhibitory effects,forming a complex immunomodulatory network together.The co-signaling network formed by PVR family members is of great significance and has become a major hot spot in hematologic tumor immunotherapy in recent years.This review describes the structure of PVR family members,their mechanism of action,research progress in hematological tumors,and their prospects for application in the immunotherapy of hematologic tumors.

Objective To explore the therapeutic effect and prognostic influencing factors of endovascular therapy for periprocedural acute ischemic stroke with large vessel occlusion(AIS-LVO)after cardiac surgery,and to analyze the pathological characteristics of thrombi leading to LVO.Methods This study retrospectively and consecutively enrolled patients who experienced AIS-LVO during the perioperative period of cardiac surgery at the Cardiovascular Surgery Department of Guangdong Provincial People's Hospital from June 1,2017,to March 31,2024.The patients were divided into a surgical group and a non-surgical group based on whether they received endovascular treatment.The clinical and imaging data of the patients were collected,including gender,age,hypertension,diabetes,history of smoking,low-density lipoprotein cholesterol,cardiac surgical methods(coronary artery bypass grafting,total arch replacement[TRA],cardiac valve replacement,other types of surgery[valve repair,atrial septal repair,ventricular septal repair,heart transplantation]),time from cardiac surgery to AIS onset,location of vascular occlusion(vertebral-basilar artery,right internal carotid artery,left internal carotid artery),National Institutes of Health stroke scale(NIHSS)score at the onset of stroke,time from stroke onset to puncture,stroke etiology(embolism,arterial dissection,atherosclerotic stenosis),and imaging data including Alberta stroke program early CT score(ASPECTS)of the anterior circulation,ASPECTS of the posterior circulation(pc-ASPECTS)and CT angiography,CT perfusion,etc.The thrombus samples were stained with hematoxylin-eosin and martius scarlet blue staining.According to the proportion of red blood cells(RBC)in the thrombus,the thrombi were classified as erythrocyte-rich thrombi(RBC proportion≥70%),mixed thrombi(RBC proportion 31%-69%),and fibrin-rich thrombi(RBC proportion≤30%).At 90d after stroke onset,the modified Rankin scale(mRS)was used for both outpatient and telephone follow-up.The mRS score 0-2 indicated a good prognosis,3-6 indicated a poor prognosis,and 6 points indicated death.Factors with P＜0.1 in univariate Logistic regression and those factors may influence the prognosis according to clinical experience were included and further analyzed with multivariate Logistic regression to analyze the 90 d prognostic influencing factors after stroke onset for AIS-LVO patients during the perioperative period of cardiac surgery.Results A total of 102 patients who experienced AIS-LVO during the perioperative period of cardiac surgery(68 males,34females,with mean age of[58±14]years)were enrolled in this study,50 were in the non-surgery group and 52 in the surgery group.(1)Significant differences were observed between the surgical and non-surgical group in hypertension(32.7%[17/52]vs.54.0%[27/50],P=0.030),NIHSS score at stroke onset(12.3[12.3,21.8]vs.35.0[18.0,35.0],P＜0.01),vascular occlusion site(P=0.048),cardiac surgery type(P＜0.01),ASPECTS/pc-ASPECTS(9[8,9]vs.4[3,6],P＜0.01),favorable90-day prognosis rate(75.0%[39/52]vs.10.0%[5/50],P＜0.01)and 90-day mortality rate(7.7%[4/52]vs.68.0%[34/50],P＜0.01).Other clinical and imaging data showed no significant differences(all P＞0.05).In the surgery group,86.5%(45/52),7.7%(4/52),and 5.8%(3/52)patients were attributed to embolism,arterial dissection,and atherosclerotic stenosis,respectively.(2)Univariate Logistic regression analysis identified NIHSS score at stroke onset,TRA,endovascular therapy,and ASPECTS/pc-ASPECTS score as prognostic factors affecting the 90-day prognosis after stroke.Set the patient's 90-day prognosis(assign favorable prognosis as 1 and poor prognosis as 0)as dependent variable,incorporate factors with P＜0.1 in the univariate Logistic analysis and location of vascular occlusion in a multivariate Logistic regression analysis.The results showed that high NIHSS score on stroke onset(OR,0.86,95%CI 0.78-0.95,P=0.002)and non endovascular therapy(OR,6.93,95%CI 1.05-45.55,P=0.044)were independent risk factors of poor prognosis 90-day after stroke onset for AIS-LVO patients during the perioperative period of cardiac surgery.(3)Among 45 cardioembolic patients,thrombus samples from 33 patients were analyzed.The analysis revealed no erythrocyte-rich thrombi,3 mixed thrombi,and 30 fibrin-rich thrombi,with 12having a fibrin proportion exceeding 90%.Conclusion Endovascular therapy improved the prognosis and reduces mortality rate in patients with periprocedural AIS-LVO after cardiac surgery,and thrombi in these patients are predominantly fibrin-rich.

OBJECTIVE To investigate the prevalence of plasma vitamin B1 deficiency in patients with sepsis and analyze the relationship between plasma vitamin B1 levels and lactic acidosis.METHODS A total of 40 patients with sepsis and 42 patients with sepsis shock admitted to the intensive care unit(ICU)of General Hospital of Ningxia Medical University from Nov.2020 to Nov.2022 were selected as the study objects.Volunteers matched by age,gender and body mass index(BMI)were selected as the healthy group.Data on gender,age,BMI,under-lying diseases,sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluation(APACHE)Ⅱ score,infection site,duration of mechanical ventilation and ICU length of stay were collected.La-boratory tests including blood routine,electrolytes,blood lactate(Lac),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),blood urea nitrogen(BUN)and serum creatinine(Scr)were performed in both groups.Plasma samples from both disease group and the healthy group were collected.High-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to measure plasma thiamine(vitamin B1)levels in the disease group on the first,third and fifth days,respectively,as well as in the healthy group.RESULTS On the first day of admission,both the sepsis group and the septic shock group exhibited vitamin B1 de-ficiency.Specifically,6 cases of vitamin B1 deficiency were observed in the patients with sepsis,while 8 cases of vitamin B1 deficiency were noted in the patients with septic shock(P=0.640).By the third and fifth days,the proportions of vitamin B1 deficiency in the sepsis group were 22.50％and 42.50％,respectively,whereas in the septic shock group,these proportions were high at 26.19％and 54.76％,with a statistically significant difference(P＜0.05).On the fifth day,in the normal liver function group,vitamin B1 levels showed a negative correlation with lactate(r=-0.590,P=0.005),whereas in the abnormal liver function group,vitamin B1 levels were pos-itively correlated with lactate(r=0.678,P=0.017).The patients in the septic shock group had low K+and ALB levels[(2.60±0.42)mmol/L and(24.56±5.78)g/L,respectively]compared to those in the sepsis group(P＜0.05).CONCLUSIONS Plasma vitamin B1 deficiency is prevalent among patients with sepsis.Changes in plasma vitamin B1 levels are closely associated with blood lactate levels in these patients.

Objective To explore the characteristics of gastric emptying in the whole process of drinking water for colonoscopy in the elderly,and to develop an elderly-friendly drinking water program,thereby improving the comfort and the quality of bowel preparation.Methods From April to September 2024,gastric ultrasound was used to monitor gastric emptying indicators in the whole process of drinking water for colonoscopy in the elderly,summa-rizing its physiological features.On this basis,in October 2024,through literature review and expert argumentation,a bowel preparation drinking water program that meets the characteristics of gastric emptying in the elderly was de-veloped.A convenience sample of 90 elderly patients scheduled for colonoscopy at 2 tertiary hospitals in Beijing was enrolled from November 2024 to January 2025.A non-concurrent controlled trial was conducted:an experimen-tal group from December 2024 to January 2025 received the new elderly-friendly drinking water program,while a control group in November 2024 followed the conventional program.Outcomes included drinking comfort assessed via Visual Analogue Scale(VAS),adverse events,total fluid intake volume and bowel preparation quality via Boston Bowel Preparation Scale(BBPS).Results The experimental group demonstrated superior VAS score(P＜0.05),bowel preparation quality(P＜0.05),total fluid intake(P＜0.05),and higher compliance with optimal stool consistency(P＜0.05),compared to the control group.The experimental group also exhibited a lower incidence of adverse events(P＜0.05).No significant difference was observed in total bowel preparation duration between 2 groups(P＞0.05).Conclusion The bowel preparation drinking water program based on the characteristics of gastric emptying in the elderly improved solution intake tolerance and bowel preparation quality,with practical implications for clinical implementation.

Objective To investigate the effects of obesity-related indexes on cardiovascular autonomic nervous function in type 2 diabetes mellitus(T2DM)patients.Methods A total of 421 T2DM patients treated in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2020 to October 2023.All the patients were divided into simple T2DM group with VFA<100 cm2(n=193)and obese group with VFA≥100 cm2(OB,n=228)according to visceral fat area(VFA).BMI,waist-to-height ratio(WHtR),waist-to-hip ratio(WHR),lipid accumulation index(LAP),visceral fat index(VAI),Chinese visceral fat index(CVAI),tapeness index(CI),body shape index(ABSI),and body roundness index(BRI)were calculated.Time domain parameters of heart rate variability(HRV)in 24 h holter electrocardiogram were recorded,including the global standard deviation(SDNN)of normal sinus RR interval,standard deviation of mean value of sinus RR interval(SDANN),root mean square difference(RMSSD)of normal continuous sinus RR interval.The percentage of adjacent RR interval difference>50 ms in total interval(PNN50),the HRV triangle index,the standard deviation of the difference of the entire adjacent NN interval length(SDSD).Results Compared with T2DM group,the OB group showed an increase in age,weight,BMI,WC,hip circumference(HC),neck circumference(NC),SBP,HbA1c,TG,SUA,CI,WHtR,WHR,VFA,SFA,VAI,LAP,CVAI,and BRI(P<0.05 or P<0.01),while a decrease in HDL-C(P<0.05).The SDNN,SDANN,SDSD,RMSSD,HRV trigonometric index,and PNN50 were lower in OB group than in T2DM group(P<0.05 or P<0.01).Spearman correlation analysis showed that SDNN and HRV trigonometric index was negatively correlated with age,DM duration,HR,SBP,PWV,WHtR,TG,SUA,VAI,LAP,BRI,VFA,LAP,and CVAI(P<0.05 or P<0.01).Logistic regression analysis shows that age,VFA,and LAP are influencing factors for cardiac autonomic dysfunction.The analysis of the working characteristic curve of the subjects showed that the area under the curve of VFA,age,and LAP in predicting cardiovascular autonomic dysfunction was 0.680,0.614,and 0.577,with sensitivity of 87.5%,41.7%,and 61.8%,and specificity of 47.3%,73.6%,and 55.6%respectively.Conclusions BMI,HC,NC,WC,TG,SFA,CI,WHtR,WHR,LAP,BRI,VAI,CVAI and VFA are closely related to cardiovascular autonomic nervous function in T2DM patients.As VFA,Ageand LAP increase,the risk of cardiovascular autonomic dysfunction increases.

BACKGROUND:Remyelination in the central nervous system is a basic repair process triggered by demyelinating events,mainly through the proliferation,migration,and differentiation of oligodendrocyte precursor cells into oligodendrocytes.The process of remyelination is affected by many factors such as astrocytes,myelin debris,microglia,macrophages,endothelial cells,pericytes,T cells,and age.OBJECTIVE:Astrocytes play an important role in regulating synaptic activity,nutritional support,and tissue repair in the central nervous system.This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.METHODS:A search was conducted on relevant literature collected from CNKI,PubMed,and Web of Science from 2014 tO 2024.The search terms were"astrocytes,oligodendrocyte precursor cells,remyelination"in both Chinese and English.Finally,66 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)The treatment of demyelinating diseases,such as multiple sclerosis,is limited to disease-modifying therapies,and there is no available method to overcome the failure of remyelination.Therefore,it is necessary to explore targets related to remyelination to promote myelin repair.(2)Remyelination is a process in which oligodendrocyte precursor cells proliferate,migrate,differentiate,and mature into oligodendrocytes,and the latter produce myelin to wrap axons to form myelin sheath.(3)Astrocytes regulate remyelination by phagocytosis of myelin debris,participating in inflammatory response,transforming into oligodendrocyte lineage cells,providing energy supply for oligodendrocyte lineage cells,releasing neurotrophic factors,and secreting extracellular matrix components.(4)The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination.Some drugs have satisfactory effects,but their effectiveness and safety still need more basic research and clinical trials to verify.(5)The mechanism of action of astrocytes in remyelination has not been fully elucidated,and the related molecular targets and signaling pathways can be further studied.