BACKGROUND:Apoptosis and autophagy imbalance in the hippocampal region of perimenopausal depressed rats are closely related to cognitive decline.Whether aerobic exercise can reduce apoptosis by promoting hippocampal autophagy and thus improve the learning and memory abilities of perimenopausal depressed rats is not clear.OBJECTIVE:To investigate the possible mechanism by which 4-week moderate-intensity treadmill exercise improves learning memory ability in ovariectomized stressed rats.METHODS:Forty Sprague-Dawely rats were randomly divided into four groups,namely,sham operation group(n=10),ovariectomized group(n=10),ovariectomized stress group(n=10)and ovariectomized stress exercise group(n=10).Except for the sham operation group,the ovaries were removed in the other three groups to establish a perimenopausal rat model,and then a depressed rat model was established by chronic unpredictable stress in the latter two groups.The rats in the ovariectomized stress exercise group underwent a 4-week moderate-intensity treadmill exercise.Tail suspension test and sucrose preference test were performed to text depression-like behaviors in rats after exercise and stress.The eight-arm maze experiment was used to test the learning and memory behaviors of rats after exercise and stress.Western blot was used to detect the protein levels of AMP-activated protein kinase/UNC-51 like autophagy activating kinase 1/mammalian target of rapamycin(AMPK/mTOR/ULK1),hippocampus apoptotic factor Caspase-3 and the protein expression of autophagy markers LC-3II/Beclin-1 in the hippocampus.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,rats in the ovariectomized and ovariectomized stress groups had prolonged resting time in the tail suspension test and decreased sugar-water intake and sugar-water preference in the sucrose preference test.(2)Ovary removal reduced the learning memory capacity of rats,as evidenced behaviorally by a significant increase in the number of working memory errors,the number of reference memory errors,and the completion time,and an even more pronounced increase in the above measures in the ovariectomized stress group.(3)Compared with the ovariectomized group,there was a significant reduction in the number of working memory errors,the number of reference memory errors,and the completion time in the ovariectomized stress group.(4)Compared with the sham operation group,in the ovariectomized and ovariectomized stress groups,the expression of hippocampal apoptotic factor Caspase 3 protein was significantly elevated,the expression of autophagy-related factors proteins Beclin-1 and LC3II,as well as the protein expression of AMPK and ULK1,was decreased,whereas the expression of mTOR protein was elevated.Changes in the above indicators were more significant in the ovariectomized stress group.(5)Compared with the ovariectomized stress group,in the ovariectomized stress exercise group,the protein expression of Caspase 3 was significantly decreased,the protein expression of Beclin-1 and LC3II was significantly increased,the protein expression of AMPK and ULK1 was significantly increased,and the protein expression of mTOR was significantly reduced.To conclude,4-week moderate-intensity treadmill exercise may promote cellular autophagy and reduce apoptosis through the AMPK/mTOR/ULK1 autophagy signaling pathway,thereby enhancing the learning and memory capacity of rats with ovariectomized depression

Objective:To investigate the possible mechanism of treadmill exercise(TR)in improving cognitive function of rats with chronic unpredictable mild stress(CUMS)by detecting pathological changes and the expression of sigma-1 receptor(SIR),endoplasmic reticulum stress-related proteins in hippocampus.Methods:30 SD rats were ran-domly allocated into control group(n=10),CUMS group(n=10)and CUMS exercise group(CUMS+TR,n=10).Subsequently,depressive model was established in rats of CUMS group and CUMS+TR group,meanwhile,CUMS+TR group rats were subjected to 4 weeks of moderate intensity treadmill exercise(20 m/min).After the CUMS and tread-mill exercise,the eight-arm radial maze test(RAM)was carried out to evaluate the learning-memory functions.Subse-quently,the pathological changes of neurons in the hippocampus of rats were measured by HE staining,the protein expression of the GRP78,IRE1,XBP1,CHOP,caspase-3 and SIR in the hippocampus were measured by Western blot.Results:Compared with the control group,the time of finishing the eight-arm radial maze prolonged and the num-ber of total memory errors increased(P＜0.05)in the RAM of the CUMS group rats.The morphology and structure of neurons in the hippocampus of CUMS group rats showed obvious pathological changes,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 significantly increased and SIR protein expression decreased(P＜0.05)in hippocampus in the CUMS group compared with the control group rats.4-week treadmill exercise significantly im-prove the learning and memory ability and pathological changes of neurons in hippocampus of CUMS+TR group rats.Compared with CUMS group rats,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 signifi-cantly decreased,the SIR expression in hippocampus significantly increased in the CUMS+TR group rats(P＜0.05).Conclusion:Treadmill exercise can improve cognitive impairment in CUMS rats,and its mechanism may be related to the up-regulation of SIR expression and the inhibition of ERS-mediated apoptosis pathway in hippocampus.

Objective:To evaluate the prognostic value of droplet digital PCR(ddPCR)in conjunction with multiparametric flow cytometry(MFC)for measurable residual disease(MRD)detection in predicting relapse risk in patients with acute myeloid leukemia(AML).Methods:In this retrospective cohort study,we have analyzed 78 newly diagnosed patients with AML who underwent combined MRD monitoring using MFC and ddPCR at The Affiliated Hospital of Hebei University(January 2018-January 2025).Clinical outcomes-including MRD negativity rates,cumulative incidence of relapse(CIR),relapse-free survival(RFS),and overall survival(OS)-were systematically evaluated.Prognostic discrim-ination between the MRD-negative and MRD-positive subgroups was compared across standalone and combined detection approaches.Results:With a median follow-up of 17 months(range:2.4-86.7)and a median of one mutation tracked per patient(range:1-3),both MFC-MRD and ddPCR-MRD negative subgroups demonstrated superior 2-year RFS compared with MRD-positive counterparts.Notably,com-bined MFC/ddPCR monitoring enhanced prognostic discrimination,with MRD-negative patients achieving significantly prolonged 2-year RFS compared with MRD-positive patients.MFC-MRD negativity independently predicted improved 2-year OS.Conclusion:ddPCR-based multi-gene MRD profiling provides significant independent prognostic value in patients with AML.The synergistic application of MFC and ddPCR enables superior predictive accuracy for relapse risk and survival outcomes,supporting its integration into standardized MRD monitoring protocols.

Objective:To explore the correlation between serum γ-glutamyl transpeptidase (γ-GGT), albumin/globulin ratio (AGR), miR-208a levels and cardiac function classification and prognosis in patients with chronic heart failure (CHF).Methods:A total of 150 CHF patients who were diagnosed in the Affiliated Hospital of Yan′an University from May 2020 to May 2023 and followed up for at least 1 year were retrospectively selected as the CHF group. Eighty healthy volunteers recruited from the physical examination center were selected as the control group. The serum levels of γ-GGT, AGR and miR-208a were compared between the two groups. Subgroup analysis was conducted according to the New York Heart Association (NYHA) classification of CHF patients and whether major adverse cardiovascular events (MACE) occurred during 1-year follow-up. Multivariate logistic regression analysis was used to screen the influencing factors of prognosis in CHF patients. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of each index for adverse prognosis of patients.Results:The serum levels of γ-GGT and miR-208a in the CHF group were significantly higher than those in the control group (all P<0.05), while the AGR level was lower than that in the control group ( P<0.05). The serum levels of γ-GGT and miR-208a in patients with NYHA class Ⅳ were significantly higher than those in patients with class Ⅱ and Ⅲ (all P<0.05), and the AGR level was lower than that in patients with class Ⅱ and Ⅲ (all P<0.05); the serum levels of γ-GGT and miR-208a in patients with NYHA class Ⅲ were significantly higher than those in patients with class Ⅱ (all P<0.05). The serum levels of γ-GGT and miR-208a in the MACE group were significantly higher than those in the non-MACE group (all P<0.05), while the AGR level was lower than that in the non-MACE group ( P<0.05). Prolonged CHF course, NYHA classification ≥class Ⅲ, decreased left ventricular ejection fraction (LVEF), complicated with atrial fibrillation, increased γ-GGT, decreased AGR and increased miR-208a were independent risk factors for adverse prognosis of CHF patients (all P<0.05). ROC curve analysis showed that the areas under the curve (AUC) of γ-GGT, AGR, miR-208a alone and in combination for predicting adverse prognosis of CHF patients were 0.631(95% CI: 0.531-0.731), 0.704(95% CI: 0.602-0.805), 0.753(95% CI: 0.657-0.849) and 0.879(95% CI: 0.818-0.941), respectively. Conclusions:Serum γ-GGT, AGR and miR-208a are closely related to NYHA classification and adverse prognosis of CHF patients. The combined application of the three indicators has important reference significance for predicting the adverse prognosis of patients.

Objective:To investigate the possible mechanism of treadmill exercise(TR)in improving cognitive function of rats with chronic unpredictable mild stress(CUMS)by detecting pathological changes and the expression of sigma-1 receptor(SIR),endoplasmic reticulum stress-related proteins in hippocampus.Methods:30 SD rats were ran-domly allocated into control group(n=10),CUMS group(n=10)and CUMS exercise group(CUMS+TR,n=10).Subsequently,depressive model was established in rats of CUMS group and CUMS+TR group,meanwhile,CUMS+TR group rats were subjected to 4 weeks of moderate intensity treadmill exercise(20 m/min).After the CUMS and tread-mill exercise,the eight-arm radial maze test(RAM)was carried out to evaluate the learning-memory functions.Subse-quently,the pathological changes of neurons in the hippocampus of rats were measured by HE staining,the protein expression of the GRP78,IRE1,XBP1,CHOP,caspase-3 and SIR in the hippocampus were measured by Western blot.Results:Compared with the control group,the time of finishing the eight-arm radial maze prolonged and the num-ber of total memory errors increased(P＜0.05)in the RAM of the CUMS group rats.The morphology and structure of neurons in the hippocampus of CUMS group rats showed obvious pathological changes,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 significantly increased and SIR protein expression decreased(P＜0.05)in hippocampus in the CUMS group compared with the control group rats.4-week treadmill exercise significantly im-prove the learning and memory ability and pathological changes of neurons in hippocampus of CUMS+TR group rats.Compared with CUMS group rats,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 signifi-cantly decreased,the SIR expression in hippocampus significantly increased in the CUMS+TR group rats(P＜0.05).Conclusion:Treadmill exercise can improve cognitive impairment in CUMS rats,and its mechanism may be related to the up-regulation of SIR expression and the inhibition of ERS-mediated apoptosis pathway in hippocampus.

BACKGROUND:Apoptosis and autophagy imbalance in the hippocampal region of perimenopausal depressed rats are closely related to cognitive decline.Whether aerobic exercise can reduce apoptosis by promoting hippocampal autophagy and thus improve the learning and memory abilities of perimenopausal depressed rats is not clear.OBJECTIVE:To investigate the possible mechanism by which 4-week moderate-intensity treadmill exercise improves learning memory ability in ovariectomized stressed rats.METHODS:Forty Sprague-Dawely rats were randomly divided into four groups,namely,sham operation group(n=10),ovariectomized group(n=10),ovariectomized stress group(n=10)and ovariectomized stress exercise group(n=10).Except for the sham operation group,the ovaries were removed in the other three groups to establish a perimenopausal rat model,and then a depressed rat model was established by chronic unpredictable stress in the latter two groups.The rats in the ovariectomized stress exercise group underwent a 4-week moderate-intensity treadmill exercise.Tail suspension test and sucrose preference test were performed to text depression-like behaviors in rats after exercise and stress.The eight-arm maze experiment was used to test the learning and memory behaviors of rats after exercise and stress.Western blot was used to detect the protein levels of AMP-activated protein kinase/UNC-51 like autophagy activating kinase 1/mammalian target of rapamycin(AMPK/mTOR/ULK1),hippocampus apoptotic factor Caspase-3 and the protein expression of autophagy markers LC-3II/Beclin-1 in the hippocampus.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,rats in the ovariectomized and ovariectomized stress groups had prolonged resting time in the tail suspension test and decreased sugar-water intake and sugar-water preference in the sucrose preference test.(2)Ovary removal reduced the learning memory capacity of rats,as evidenced behaviorally by a significant increase in the number of working memory errors,the number of reference memory errors,and the completion time,and an even more pronounced increase in the above measures in the ovariectomized stress group.(3)Compared with the ovariectomized group,there was a significant reduction in the number of working memory errors,the number of reference memory errors,and the completion time in the ovariectomized stress group.(4)Compared with the sham operation group,in the ovariectomized and ovariectomized stress groups,the expression of hippocampal apoptotic factor Caspase 3 protein was significantly elevated,the expression of autophagy-related factors proteins Beclin-1 and LC3II,as well as the protein expression of AMPK and ULK1,was decreased,whereas the expression of mTOR protein was elevated.Changes in the above indicators were more significant in the ovariectomized stress group.(5)Compared with the ovariectomized stress group,in the ovariectomized stress exercise group,the protein expression of Caspase 3 was significantly decreased,the protein expression of Beclin-1 and LC3II was significantly increased,the protein expression of AMPK and ULK1 was significantly increased,and the protein expression of mTOR was significantly reduced.To conclude,4-week moderate-intensity treadmill exercise may promote cellular autophagy and reduce apoptosis through the AMPK/mTOR/ULK1 autophagy signaling pathway,thereby enhancing the learning and memory capacity of rats with ovariectomized depression

Objective:To evaluate the prognostic value of droplet digital PCR(ddPCR)in conjunction with multiparametric flow cytometry(MFC)for measurable residual disease(MRD)detection in predicting relapse risk in patients with acute myeloid leukemia(AML).Methods:In this retrospective cohort study,we have analyzed 78 newly diagnosed patients with AML who underwent combined MRD monitoring using MFC and ddPCR at The Affiliated Hospital of Hebei University(January 2018-January 2025).Clinical outcomes-including MRD negativity rates,cumulative incidence of relapse(CIR),relapse-free survival(RFS),and overall survival(OS)-were systematically evaluated.Prognostic discrim-ination between the MRD-negative and MRD-positive subgroups was compared across standalone and combined detection approaches.Results:With a median follow-up of 17 months(range:2.4-86.7)and a median of one mutation tracked per patient(range:1-3),both MFC-MRD and ddPCR-MRD negative subgroups demonstrated superior 2-year RFS compared with MRD-positive counterparts.Notably,com-bined MFC/ddPCR monitoring enhanced prognostic discrimination,with MRD-negative patients achieving significantly prolonged 2-year RFS compared with MRD-positive patients.MFC-MRD negativity independently predicted improved 2-year OS.Conclusion:ddPCR-based multi-gene MRD profiling provides significant independent prognostic value in patients with AML.The synergistic application of MFC and ddPCR enables superior predictive accuracy for relapse risk and survival outcomes,supporting its integration into standardized MRD monitoring protocols.

Objective:To explore the correlation between serum γ-glutamyl transpeptidase (γ-GGT), albumin/globulin ratio (AGR), miR-208a levels and cardiac function classification and prognosis in patients with chronic heart failure (CHF).Methods:A total of 150 CHF patients who were diagnosed in the Affiliated Hospital of Yan′an University from May 2020 to May 2023 and followed up for at least 1 year were retrospectively selected as the CHF group. Eighty healthy volunteers recruited from the physical examination center were selected as the control group. The serum levels of γ-GGT, AGR and miR-208a were compared between the two groups. Subgroup analysis was conducted according to the New York Heart Association (NYHA) classification of CHF patients and whether major adverse cardiovascular events (MACE) occurred during 1-year follow-up. Multivariate logistic regression analysis was used to screen the influencing factors of prognosis in CHF patients. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of each index for adverse prognosis of patients.Results:The serum levels of γ-GGT and miR-208a in the CHF group were significantly higher than those in the control group (all P<0.05), while the AGR level was lower than that in the control group ( P<0.05). The serum levels of γ-GGT and miR-208a in patients with NYHA class Ⅳ were significantly higher than those in patients with class Ⅱ and Ⅲ (all P<0.05), and the AGR level was lower than that in patients with class Ⅱ and Ⅲ (all P<0.05); the serum levels of γ-GGT and miR-208a in patients with NYHA class Ⅲ were significantly higher than those in patients with class Ⅱ (all P<0.05). The serum levels of γ-GGT and miR-208a in the MACE group were significantly higher than those in the non-MACE group (all P<0.05), while the AGR level was lower than that in the non-MACE group ( P<0.05). Prolonged CHF course, NYHA classification ≥class Ⅲ, decreased left ventricular ejection fraction (LVEF), complicated with atrial fibrillation, increased γ-GGT, decreased AGR and increased miR-208a were independent risk factors for adverse prognosis of CHF patients (all P<0.05). ROC curve analysis showed that the areas under the curve (AUC) of γ-GGT, AGR, miR-208a alone and in combination for predicting adverse prognosis of CHF patients were 0.631(95% CI: 0.531-0.731), 0.704(95% CI: 0.602-0.805), 0.753(95% CI: 0.657-0.849) and 0.879(95% CI: 0.818-0.941), respectively. Conclusions:Serum γ-GGT, AGR and miR-208a are closely related to NYHA classification and adverse prognosis of CHF patients. The combined application of the three indicators has important reference significance for predicting the adverse prognosis of patients.

Objective:To summary the clinical phenotype and genotype characteristics of 2 cases of autosomal dominant mental retardation (MRD) caused by TRIO gene variation. Methods:Retrospective study of the clinical data of 2 cases of autosomal dominant MRD caused by TRIO gene mutations diagnosed at the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in April 2019 and January 2023 was conducted. The clinical features were summarized and gene analysis and follow-up were carried out. Results:The 2 patients were 6 years and 5 months old and 5 months old males, respectively. Clinical manifestations included seizures, cognitive and motor disorders, low intelligent development; case 1 had microcephaly, attention deficit disorder, ataxia, and aggressive behavior, and case 2 had macrocephaly. Brain magnetic resonance imaging revealed cerebellar atrophy in case 1, and non-specific dilation of the subarachnoid space and hypoplasia of the corpus callosum in case 2. Analysis of chromosome karyotype and chromosome copy number variation in 2 children showed no abnormalities. Whole exome sequencing revealed novel missense mutations in the TRIO gene in both patients [NM_007118:c.4289C>A(p.Thr1430Lys), c.4111C>A(p.His1371Asn), respectively]. The application of rehabilitation function training and a variety of anti-seizure medications can not fully and effectively control the seizure. Conclusion:TRIO gene c.4289C>A(p.Thr1430Lys), c.4111C>A(p.His1371Asn) de novo missense variants were the genetic etiology of the 2 probands,causing rare autosomal dominant MRD type 44 and 63.

Glaucoma is a neurodegenerative disease characterized by progressive and irreversible necrosis and apopto-sis of retinal ganglion cells.The abnormal activation of microglia,astrocytes and Müller cells in the central nervous system of the retina and macrophages,T/B lymphocytes and regulatory T cells in the peripheral immune system is involved in the pathogenesis of glaucoma,and the secretion of inflammatory factors such as interleukin 6 and interleukin 8 is closely relat-ed to the development of glaucoma.In this paper,the role of immune cells of the central nervous system and peripheral im-mune system of the retina and the inflammatory factors they secreted in the development of glaucoma is reviewed,in order to understand the pathogenesis of glaucoma at the cellular and molecular levels and to provide ideas for exploring new treatment methods.