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 evaluate the platelet transfusion requirements in children with high-risk stage Ⅳ neuroblastoma undergoing autologous hematopoietic stem cell transplantation (ASCT), and to identify risk factors for increased transfusion needs and prolonged time to platelet transfusion independence. Methods: This single-center retrospective clinical study included 96 children with high-risk stage Ⅳ neuroblastoma who underwent ASCT from January 2019 to May 2024 in our hospital. Relevant clinical data were collected and analyzed, including age, gender, body surface area, platelet count (PLT) on stem cell infusion day (day 0), conditioning regimen, CD34 stem cell dose, platelet transfusion requirements during transplantation, and time to platelet transfusion independence post-transplant. Results: All 96 (100%) children received transfusion after ASCT. From day 0 to transfusion independence, the median number of platelet transfusion was 3 (2, 4.50), and the median volume of platelet transfused was 3 (2, 4.25) units. Platelet transfusion was required in almost all children in pseudo-healing stage (day 4 to day 6) and polar stage (day 7 to day 14), with transfusion rates as high as 83.33%(n=80) and 100%(n=96), respectively. The median time to platelet transfusion independence post-transplant was 13(11,17) days. Multivariate analysis showed that PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, the use of “busulfan+ melphalan” conditioning regimen, and CD34 stem cell dose<4.0×10 /kg were associated with significantly increased platelet requirements and numbers of transfusion (P<0.05). PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, and CD34 stem cell dose<4.0×10 /kg were associated with significantly delayed platelet transfusion independence (P<0.05). Age, sex, and blood type showed no statistically significant association (P>0.05) with post-transplant platelet transfusion requirements or time to transfusion independence in neuroblastoma patients. Conclusion: This study provided quantitative data for platelet transfusion after ASCT in children with high-risk stage Ⅳ neuroblastoma, and identified PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, CD34 stem cell dose<4.0×10 /kg were risk factors for increased platelet transfusions and delayed transfusion independence. Furthermore, the use of the BuMel (busulfan-melphalan) conditioning regimen was also found to contribute to increased transfusion requirements.

Objective: To evaluate the platelet transfusion requirements in children with high-risk stage Ⅳ neuroblastoma undergoing autologous hematopoietic stem cell transplantation (ASCT), and to identify risk factors for increased transfusion needs and prolonged time to platelet transfusion independence. Methods: This single-center retrospective clinical study included 96 children with high-risk stage Ⅳ neuroblastoma who underwent ASCT from January 2019 to May 2024 in our hospital. Relevant clinical data were collected and analyzed, including age, gender, body surface area, platelet count (PLT) on stem cell infusion day (day 0), conditioning regimen, CD34 stem cell dose, platelet transfusion requirements during transplantation, and time to platelet transfusion independence post-transplant. Results: All 96 (100%) children received transfusion after ASCT. From day 0 to transfusion independence, the median number of platelet transfusion was 3 (2, 4.50), and the median volume of platelet transfused was 3 (2, 4.25) units. Platelet transfusion was required in almost all children in pseudo-healing stage (day 4 to day 6) and polar stage (day 7 to day 14), with transfusion rates as high as 83.33%(n=80) and 100%(n=96), respectively. The median time to platelet transfusion independence post-transplant was 13(11,17) days. Multivariate analysis showed that PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, the use of “busulfan+ melphalan” conditioning regimen, and CD34 stem cell dose<4.0×10 /kg were associated with significantly increased platelet requirements and numbers of transfusion (P<0.05). PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, and CD34 stem cell dose<4.0×10 /kg were associated with significantly delayed platelet transfusion independence (P<0.05). Age, sex, and blood type showed no statistically significant association (P>0.05) with post-transplant platelet transfusion requirements or time to transfusion independence in neuroblastoma patients. Conclusion: This study provided quantitative data for platelet transfusion after ASCT in children with high-risk stage Ⅳ neuroblastoma, and identified PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, CD34 stem cell dose<4.0×10 /kg were risk factors for increased platelet transfusions and delayed transfusion independence. Furthermore, the use of the BuMel (busulfan-melphalan) conditioning regimen was also found to contribute to increased transfusion requirements.

Objective:To explore effects and mechanism of Hydroxylsafflower Yellow A(HSYA)on expression of NLRP3 in glial cells after cerebral ischemic injury.Methods:A middle cerebral artery occlusion/reperfusion(MCAO/R)model was established in male SD rats.After successfully modeling for 24 h,Longa scoring and corner test were used to evaluate degree of neurological dys-function.Western blot and immunofluorescence were used to detect expressions of JAK2/STAT3 molecules and NLRP3,ELISA was used to measure IL-1β,IL-6 and TNF-α levels.A glucose-oxygen deprivation/reperfusion(OGD/R)model was established in microg-lia,and JAK2 and STAT3 inhibitor AG490 was used to further verify action of HSYA on NLRP3.Results:Compared with sham group,neurological dysfunction aggravated in MCAO/R group(P<0.01),HSYA treatment improved neurological function(P<0.01).Expres-sions of p-JAK2,p-STAT3 and NLRP3 in MCAO/R group were higher than those in the sham group(P<0.01);and HSYA treatment reduced expressions of p-JAK2,p-STAT3 and NLRP3(P<0.01).Levels of inflammatory factors IL-1β,IL-6 and TNF-α were higher in MCAO/R group than sham group(P<0.01),and HSYA inhibited expressions of IL-1β,IL-6 and TNF-α(P<0.01 or P<0.05).In vi-tro experiments showed expressions of p-JAK2,p-STAT3 and NLRP3 in OGD/R group were significantly higher than normal control group(P<0.01),after adding AG490,phosphorylation of JAK2 and STAT3 decreased,NLRP3 expression was inhibited(P<0.01).Inflammatory cytokines IL-1β,IL-6 and TNF-α levels were higher in OGD/R group than normal control group(P<0.01),and HSYA inhibited expressions of IL-1β,IL-6 and TNF-α(P<0.01 or P<0.05).Conclusion:HSYA alleviates brain damage,probably by regu-lating JAK2/STAT3 signaling pathway and inhibiting NLRP3 expression in microglia after cerebral ischemia and hypoxia.

Objective To investigate the association between body roundness index(BRI)and hyperuricemia(HUA)in patients with type 2 diabetes mellitus(T2DM).Methods 555 T2DM inpatients were selected from July 2022 to October 2023 in Gansu Province People's Hospital Endocrinology.According to BRI,the T2DM patients were divided into four group:low BRI(L-BRI,BRI≤3.579,n=140)group,moderate BRI(M-BRI,3.579

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.