1.Mechanism by which esketamine improves postoperative cognitive impairment in rats with hip fracture through AMPK/SIRT1/PGC-1α signaling pathway
Xuan LIU ; Xiaomin ZHANG ; Jinting LIU ; Yan HAO ; Yeming WANG ; Lixing CHEN
China Pharmacy 2025;36(21):2674-2680
OBJECTIVE To investigate the mechanism by which esketamine improves postoperative cognitive impairment in rats with hip fracture based on the AMP-activated protein kinase (AMPK)/silencing information regulatory factor 1 (SIRT1)/ peroxisome proliferator activated-receptor-γ coactivator-1α (PGC-1α) signaling pathway. METHODS Rats with hip fracture surgery were assigned into model group, esketamine group (10 mg/kg), inhibitor group (250 μg/mL AMPK inhibitor Compound C), and esketamine+inhibitor group (10 mg/kg esketamine + 250 μg/mL Compound C), and rats undergoing sham surgery were used as the control group, with 12 rats in each group. New object recognition and Barnes maze experiments were used to E-mail:448231@163.com evaluate cognitive function in rats. The levels of serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β),superoxide dismutase (SOD), malondialdehyde (MDA), gamma-aminobutyric acid (GABA), dopamine (DA) and glutamate (Glu), and the apoptosis of hippocampal neurons were detected. The pathological morphology of the hippocampal tissue and the ultrastructure of mitochondria were observed. The mRNA expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax),the mRNA and protein expression of AMPK, SIRT1 and PGC-1α, as well as the expression of phosphorylated (p)-AMPK in hippocampal tissue, were detected. RESULTS Compared with the control group, the hippocampal neurons in the model group of rats were disordered, with more neurons necrotic and swollen mitochondria;the new object recognition index, the SOD, GABA, DA levels, Bcl-2, AMPK, SIRT1 and PGC-1α mRNA expression levels, and p-AMPK, SIRT1, PGC-1α protein expression levels were significantly reduced, while the latency and number of errors for locating unknown holes, the TNF-α, IL-1β, MDA and Glu levels, neuronal cell apoptosis rate, and Bax mRNA expression levels were significantly increased/prolonged (P<0.05). Compared with the model group, the esketamine group showed reduced pathological damage to the hippocampal tissue of rats, and the new object recognition index, the SOD, GABA and DA levels, the Bcl-2, AMPK, SIRT1 and PGC-1α mRNA expression levels, and p-AMPK, SIRT1, PGC-1α protein expression levels were significantly increased,while the latency and error frequency for locating unknown holes, TNF-α, IL-1β, MDA and Glu levels, neuronal cell apoptosis rate, and Bax mRNA expression levels were significantly decreased (P<0.05);the inhibitor group showed the opposite trend of changes in these indicators compared to the esketamine group (P<0.05).AMPK inhibitor could reverse the improvement effect of esketamine on the above indicators after hip fracture surgery in rats (P<0.05). CONCLUSIONS Esketamine may improve postoperative inflammatory response and oxidative stress levels in rats with hip fracture by activating the AMPK/SIRT1/PGC-1α signaling pathway, inhibiting neuronal cell apoptosis, improving mitochondrial structure, and promoting postoperative cognitive function recovery.
2.Clinicopathological features and short-term prognosis of negative triple-biomarker hepatocellular carcinoma
Chengwei WANG ; Yeming ZHOU ; Wei JIANG ; Yongfei HUA
Chinese Journal of Postgraduates of Medicine 2025;48(9):809-815
Objective:To explore the prognosis and influencing factors of hepatocellular carcinoma patients with negative triple-biomarker after surgery.Methods:Two hundred patients undergoing surgeries for hepatocellular carcinoma with complete clinicopathological data from Lihuili Hospital Affiliated to Ningbo University from January 2020 to December 2021 were retrospectively analyzed, and their clinicopathological features, postoperative recurrence and prognosis were analyzed.Results:Among the 200 hepatocellular carcinoma patients, 54 cases were triple-negative type, 88 cases were protein induced by vitamin K absence-Ⅱ (PIVKA-Ⅱ) type, 51 cases were alpha-fetoprotein (AFP) type and 7 cases were alpha-fetoprotein Lens culinaris aggluyinin-reactive fraction 3 (AFP-L3) type. Due to the limited cases of AFP-L3 type, patients with this type were not included in this study. The recurrence rates were 29.6% (16/54), 40.9% (36/88) and 41.2% (21/51) for tripe-negative type, PIVKA-Ⅱ type and AFP type, respectively, the corresponding median recurrence-free survival time was 25.8, 10.6 and 10.0 months, respectively, and there were statistical differences ( P<0.05). The median overall survival time of tripe-negative type, PIVKA-Ⅱ type and AFP type was 40.7, 40.0 and 36.6 months, respectively, without statistical difference ( P>0.05). Univariate analysis showed that tumor diameter, tumor differentiation degree, and capsule or were not factors affecting patients′ overall survival time after surgery. Postoperative albumin, tumor diameter, tumor differentiation degree, capsule or not, and microvascular invasion were factors affecting patients′ recurrence-free survival time after surgery. Multivariate analysis showed that low tumor differentiation and no envelope were independent risk factors for patients′overall survival time after surgery. Tumor long diameter>5 cm, low differentiation, no envelope, preoperative hypoproteinemia and non-tripe-negative type were independent risk factors for patients′ recurrence-free survival time after surgery. Conclusions:The short-term postoperative recurrence rate for triple-negative hepatocellular carcinoma is low, and the correlation with long-term prognosis remains to be evaluated.
3.Rehabilitation effect of individual computer magnanimous therapy on patients with end-stage renal disease undergoing maintenance hemodialysis
Lanlan WU ; Junjie WANG ; Yunfang ZHANG ; Xuewei HUANG ; Yanyan SU ; Yeming LEI ; Yumin LI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(8):698-705
Objective:To explore the rehabilitation effects of individual computer story-version magnanimous therapy (ICSMT) on patients with end-stage renal disease undergoing maintenance hemodialysis (MHD).Methods:A total of 120 patients with end-stage renal disease receiving MHD treatment at the Department of Nephrology Hemodialysis Center of Huadu District People's Hospital of Guangzhou from August 2022 to April 2024 were selected as the study subjects.They were randomly divided into control group ( n=60, receiving routine clinical treatment) and ICSMT group ( n=60, receiving routine clinical treatment combined with ICSMT for psychological intervention) by random number table method.The patients in the two groups were evaluated by the self-rating anxiety scale (SAS), self-rating depression scale (SDS), enterprising and magnanimous questionnaire (EMQ), the short-form-36 health survey (SF-36), and activity of daily living scale (ADL) before intervention and at 4-week post-intervention.Blood pressure, blood urea nitrogen (BUN), hemoglobin (Hb), and serum albumin (ALB) levels were also measured before the intervention and at the 4-week post-intervention.The clinical global impression scale (CGI) was used to evaluate clinical efficacy before the intervention, at the 2-week post-intervention, and at the 4-week post-intervention.Statistics analysis was performed using SPSS 29.0.1.0(171). Independent-samples t-test, paired t-test, Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Results:After 4 weeks of intervention, the SAS and SDS in the ICSMT group (49.0 (48.0, 50.0), 50.0 (49.0, 51.0)) were significantly lower than those in the control group (51.0 (50.0, 52.0), 52.0 (51.0, 53.0)) (both P<0.001). The enterprising subscore of the EMQ in the ICSMT group (35.0 (32.0, 37.0)) was significantly higher than that in the control group (31.0 (29.0, 34.0)) ( P<0.001). Furthermore, the differences of enterprising and magnanimous subscores between the two groups before and after intervention in the ICSMT group (2.0 (1.0, 4.0), 1.0 (-1.0, 2.0))were significantly higher than those in the control group (-1.0 (-1.0, 0), -1.0 (-1.2, 0)) (both P<0.05). Systolic and diastolic blood pressure values in the ICSMT group (130 (126, 134) mmHg, 85 (80, 88) mmHg)were significantly lower than those in the control group (145 (138, 152) mmHg, 93 (88, 99) mmHg)(1 mmHg=0.133 kPa) after 4 weeks of intervention(both P<0.05). After 4 weeks of intervention, the level of BUN in the ICSMT group (5.5 (3.7, 8.4) mmol/L) was significantly lower than that in the control group (9.1 (6.8, 11.4) mmol/L), while the level of Hb and ALB in the ICSMT group ((115.0±10.0)g/L, (38.3±3.2)g/L)were significantly higher than those in the control group ((104.0±12.0)g/L, (37.1±2.9)g/L) (all P<0.05). After 4 weeks of intervention, the physical functioning, role-physical, general health, vitality, social functioning, role-emotional, and mental health subscores of SF-36 in ICSMT group were all significantly higher than those in the control group (all P<0.05). After 4 weeks of intervention, the score of ADL in the ICSMT group (15.42±1.58)was significantly lower than that in the control group (16.78±2.06) ( t=-4.08, P<0.05). At the 2-week post-intervention and the 4-week post-intervention, the severity of illness (SI) and global improvement (GI) in the ICSMT group were significantly lower than those in the control group, while the efficacy index (EI) in the ICSMT group was significantly higher than that in the control group (all P<0.05). Conclusion:ICSMT can effectively promote the physical, psychological, and social functional rehabilitation of end-stage renal disease patients undergoing MHD, significantly improving their quality of life.
4.Precision-driven imaging assessment of traumatic fractures in the era of personalized medicine
Xuan WEI ; Yeming ZHONG ; Zigang CHE ; Yuchen CHEN ; Hao WANG ; Pengfei ZHAO
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(4):343-347
Traumatic injuries represent the fifth leading cause of death in China and the primary cause of death among young adults. While facial fractures can lead to significant aesthetic and psychological consequences, fractures in the limbs and joints impair functional mobility. In traumatic incidents requiring forensic evaluation, such as traffic accidents or violent conflicts, the type and severity of fractures directly determine injury grading and disability assessment. Consequently, the accurate diagnosis of traumatic fractures is not only a critical medical issue impacting patient management and rehabilitation but also a significant social issue influencing judicial fairness. This article systematically reviews advancements in multi-modal imaging techniques. While conventional X-ray radiography remains a fundamental screening tool, it faces challenges in detecting occult fractures. Multi-slice spiral computed tomography (MSCT), utilizing 3D reconstruction, enables spatial analysis of complex fractures. Magnetic resonance imaging (MRI), with its multi-sequence capabilities, plays an indispensable role in detecting bone marrow edema and assessing concomitant soft tissue injuries. Regarding innovative technologies, dual-energy computed tomography (DECT) employs virtual non-calcium (VNC) techniques for quantitative bone marrow edema analysis; ultra-high-resolution computed tomography (U-HRCT) breaks through imaging limitations of trabecular microarchitecture with a resolution of approximately 10 μm; and 7.0 T ultra-high-field MRI, alongside MRI-based CT-like imaging techniques, advances radiation-free bone structure evaluation. Artificial intelligence (AI) models significantly enhance diagnostic efficiency in fracture detection. Future developments will focus on multi-modal image fusion, the construction of intelligent decision-support systems, and the quantitative functional assessment of bone microstructure, facilitating a paradigm shift from anatomical description to prognostic prediction and realizing the principles of personalized medicine.
5.Rehabilitation effect of individual computer magnanimous therapy on patients with end-stage renal disease undergoing maintenance hemodialysis
Lanlan WU ; Junjie WANG ; Yunfang ZHANG ; Xuewei HUANG ; Yanyan SU ; Yeming LEI ; Yumin LI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(8):698-705
Objective:To explore the rehabilitation effects of individual computer story-version magnanimous therapy (ICSMT) on patients with end-stage renal disease undergoing maintenance hemodialysis (MHD).Methods:A total of 120 patients with end-stage renal disease receiving MHD treatment at the Department of Nephrology Hemodialysis Center of Huadu District People's Hospital of Guangzhou from August 2022 to April 2024 were selected as the study subjects.They were randomly divided into control group ( n=60, receiving routine clinical treatment) and ICSMT group ( n=60, receiving routine clinical treatment combined with ICSMT for psychological intervention) by random number table method.The patients in the two groups were evaluated by the self-rating anxiety scale (SAS), self-rating depression scale (SDS), enterprising and magnanimous questionnaire (EMQ), the short-form-36 health survey (SF-36), and activity of daily living scale (ADL) before intervention and at 4-week post-intervention.Blood pressure, blood urea nitrogen (BUN), hemoglobin (Hb), and serum albumin (ALB) levels were also measured before the intervention and at the 4-week post-intervention.The clinical global impression scale (CGI) was used to evaluate clinical efficacy before the intervention, at the 2-week post-intervention, and at the 4-week post-intervention.Statistics analysis was performed using SPSS 29.0.1.0(171). Independent-samples t-test, paired t-test, Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Results:After 4 weeks of intervention, the SAS and SDS in the ICSMT group (49.0 (48.0, 50.0), 50.0 (49.0, 51.0)) were significantly lower than those in the control group (51.0 (50.0, 52.0), 52.0 (51.0, 53.0)) (both P<0.001). The enterprising subscore of the EMQ in the ICSMT group (35.0 (32.0, 37.0)) was significantly higher than that in the control group (31.0 (29.0, 34.0)) ( P<0.001). Furthermore, the differences of enterprising and magnanimous subscores between the two groups before and after intervention in the ICSMT group (2.0 (1.0, 4.0), 1.0 (-1.0, 2.0))were significantly higher than those in the control group (-1.0 (-1.0, 0), -1.0 (-1.2, 0)) (both P<0.05). Systolic and diastolic blood pressure values in the ICSMT group (130 (126, 134) mmHg, 85 (80, 88) mmHg)were significantly lower than those in the control group (145 (138, 152) mmHg, 93 (88, 99) mmHg)(1 mmHg=0.133 kPa) after 4 weeks of intervention(both P<0.05). After 4 weeks of intervention, the level of BUN in the ICSMT group (5.5 (3.7, 8.4) mmol/L) was significantly lower than that in the control group (9.1 (6.8, 11.4) mmol/L), while the level of Hb and ALB in the ICSMT group ((115.0±10.0)g/L, (38.3±3.2)g/L)were significantly higher than those in the control group ((104.0±12.0)g/L, (37.1±2.9)g/L) (all P<0.05). After 4 weeks of intervention, the physical functioning, role-physical, general health, vitality, social functioning, role-emotional, and mental health subscores of SF-36 in ICSMT group were all significantly higher than those in the control group (all P<0.05). After 4 weeks of intervention, the score of ADL in the ICSMT group (15.42±1.58)was significantly lower than that in the control group (16.78±2.06) ( t=-4.08, P<0.05). At the 2-week post-intervention and the 4-week post-intervention, the severity of illness (SI) and global improvement (GI) in the ICSMT group were significantly lower than those in the control group, while the efficacy index (EI) in the ICSMT group was significantly higher than that in the control group (all P<0.05). Conclusion:ICSMT can effectively promote the physical, psychological, and social functional rehabilitation of end-stage renal disease patients undergoing MHD, significantly improving their quality of life.
6.Clinicopathological features and short-term prognosis of negative triple-biomarker hepatocellular carcinoma
Chengwei WANG ; Yeming ZHOU ; Wei JIANG ; Yongfei HUA
Chinese Journal of Postgraduates of Medicine 2025;48(9):809-815
Objective:To explore the prognosis and influencing factors of hepatocellular carcinoma patients with negative triple-biomarker after surgery.Methods:Two hundred patients undergoing surgeries for hepatocellular carcinoma with complete clinicopathological data from Lihuili Hospital Affiliated to Ningbo University from January 2020 to December 2021 were retrospectively analyzed, and their clinicopathological features, postoperative recurrence and prognosis were analyzed.Results:Among the 200 hepatocellular carcinoma patients, 54 cases were triple-negative type, 88 cases were protein induced by vitamin K absence-Ⅱ (PIVKA-Ⅱ) type, 51 cases were alpha-fetoprotein (AFP) type and 7 cases were alpha-fetoprotein Lens culinaris aggluyinin-reactive fraction 3 (AFP-L3) type. Due to the limited cases of AFP-L3 type, patients with this type were not included in this study. The recurrence rates were 29.6% (16/54), 40.9% (36/88) and 41.2% (21/51) for tripe-negative type, PIVKA-Ⅱ type and AFP type, respectively, the corresponding median recurrence-free survival time was 25.8, 10.6 and 10.0 months, respectively, and there were statistical differences ( P<0.05). The median overall survival time of tripe-negative type, PIVKA-Ⅱ type and AFP type was 40.7, 40.0 and 36.6 months, respectively, without statistical difference ( P>0.05). Univariate analysis showed that tumor diameter, tumor differentiation degree, and capsule or were not factors affecting patients′ overall survival time after surgery. Postoperative albumin, tumor diameter, tumor differentiation degree, capsule or not, and microvascular invasion were factors affecting patients′ recurrence-free survival time after surgery. Multivariate analysis showed that low tumor differentiation and no envelope were independent risk factors for patients′overall survival time after surgery. Tumor long diameter>5 cm, low differentiation, no envelope, preoperative hypoproteinemia and non-tripe-negative type were independent risk factors for patients′ recurrence-free survival time after surgery. Conclusions:The short-term postoperative recurrence rate for triple-negative hepatocellular carcinoma is low, and the correlation with long-term prognosis remains to be evaluated.
7.Precision-driven imaging assessment of traumatic fractures in the era of personalized medicine
Xuan WEI ; Yeming ZHONG ; Zigang CHE ; Yuchen CHEN ; Hao WANG ; Pengfei ZHAO
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(4):343-347
Traumatic injuries represent the fifth leading cause of death in China and the primary cause of death among young adults. While facial fractures can lead to significant aesthetic and psychological consequences, fractures in the limbs and joints impair functional mobility. In traumatic incidents requiring forensic evaluation, such as traffic accidents or violent conflicts, the type and severity of fractures directly determine injury grading and disability assessment. Consequently, the accurate diagnosis of traumatic fractures is not only a critical medical issue impacting patient management and rehabilitation but also a significant social issue influencing judicial fairness. This article systematically reviews advancements in multi-modal imaging techniques. While conventional X-ray radiography remains a fundamental screening tool, it faces challenges in detecting occult fractures. Multi-slice spiral computed tomography (MSCT), utilizing 3D reconstruction, enables spatial analysis of complex fractures. Magnetic resonance imaging (MRI), with its multi-sequence capabilities, plays an indispensable role in detecting bone marrow edema and assessing concomitant soft tissue injuries. Regarding innovative technologies, dual-energy computed tomography (DECT) employs virtual non-calcium (VNC) techniques for quantitative bone marrow edema analysis; ultra-high-resolution computed tomography (U-HRCT) breaks through imaging limitations of trabecular microarchitecture with a resolution of approximately 10 μm; and 7.0 T ultra-high-field MRI, alongside MRI-based CT-like imaging techniques, advances radiation-free bone structure evaluation. Artificial intelligence (AI) models significantly enhance diagnostic efficiency in fracture detection. Future developments will focus on multi-modal image fusion, the construction of intelligent decision-support systems, and the quantitative functional assessment of bone microstructure, facilitating a paradigm shift from anatomical description to prognostic prediction and realizing the principles of personalized medicine.
8.MiRNA-103-3p promotes neural cell autophagy by activating Wnt/β-catenin signaling via targeting rab10 in a rat model of depression
Yeming ZHANG ; Yuanxiang ZHANG ; Xuebin SHEN ; Guodong WANG ; Lei ZHU
Journal of Southern Medical University 2024;44(7):1315-1326
Objective To explore the neuroprotective role of Rab10 gene in depression and the mechanism mediating its effect.Methods Forty-eight male SD rats were randomized into a control group and 3 chronic unpredictable mild stress(CUMS)groups(n=12).The rats in the latter 3 groups were subjected to injections of normal saline,an adeno-associated viral(AAV)vector,or a Rab10-overexpressing AAV vector in the lateral ventricle after CUMS modeling.The depressive behavioral changes of the rats were assessed using behavioral tests.The TargetScan database was used to predict the miRNA interacting with Rab10 and the binding sites.The interaction between miRNA-103-3p and Rab10 was investigated using dual-luciferase and radioimmunoprecipitation(RIP)assay.The effect of corticosterone treatment on PC12 cell viability was assessed with CCK-8 assay.In corticosterone-stimulated PC12 cells,the changes in BDNF,CREB,p62,Beclin-1,Wnt3a,Gsk3β,phosphorylated(p)-Gsk3β,and β-catenin protein expressions following transfection with the Rab10-overexpressing AAV vector and a miRNA-103-3p inhibitor,alone or in combination,were analyzed using qRT-PCR and Western blotting.Results Injection of Rab10-overexpressing AVV vector into the lateral ventricle significantly improved depressive behaviors of CUMS rats.The mRNA and proteins expression of Rab10 were significantly down-regulated in the hippocampus of CUMS rats and in corticosterone-stimulated PC12 cells.Bioinformatics analysis and the results of double luciferase and RIP experiments confirmed the targeting relationship between miRNA-103-3p and Rab10.In PC12 cells,overexpression of Rab10 or silencing miRNA-103-3p activated the Wnt/β-catenin signaling pathway,up-regulated the expressions of BDNF,CREB and Beclin-1,and down-regulated the expression of p62 protein;silencing Rab10 obviously blocked the effect of miRNA-103-3p inhibitor.Conclusion In mouse models of depression,miRNA-103-3p activates Wnt/β-catenin signaling via targeting rab10 to improve neural plasticity and promotes neural cell autophagy.
9.Comparative study on the prognosis of hepatolithiasis and hepatitis B virus-associated intrahepatic cholangiocarcinoma
Yeming ZHOU ; Wei JIANG ; Shuqi MAO ; Changjiang LU ; Jing HUANG ; Shengdong WU ; Chunnian WANG ; Caide LU
Chinese Journal of Hepatobiliary Surgery 2024;30(11):840-844
Objective:To compare the prognosis of patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV)-associated ICC after radical resection.Methods:The clinicopathological and survival data of 69 patients with ICC undergoing radical resection in the Department of Hepatobiliary and Pancreatic Surgery, Lihuili Hospital Affiliated to Ningbo University from January 2012 to February 2024 were retrospectively analyzed, including 40 males and 29 females, aged (62.9±10.2) years. Patients were divided into the stone group ( n=40, with hepatolithiasis) and HBV group ( n=29, with HBV). Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival rate comparison. Cox proportional hazard regression model was used for multivariate analysis to analyze the effect of hepatolithiasis and HBV on the prognosis. Results:The median overall survival of ICC patients in the stone group was 16 months, and that in the HBV group was 27 months. The 1-, 3-, and 5-year cumulative survivals of the stone group were 56.6%, 23.2%, and 10.3%, respectively, which were lower than those of the HBV group (72.0%, 50.7%, and 43.4%, respectively, χ2=5.95, P=0.015). The median recurrence-free survivals (RFS) of the stone group and the HBV group were 12 months and 23 months, respectively. The 1-year and 3-year RFS of the stone group were 49.2% and 18.1%, which were lower than those of the HBV group (65.0% and 39.8%, respectively, χ2=3.94, P=0.047). Univariate analysis showed that hepatolithiasis was assciated with prognosis ( χ2=5.95, P=0.015). Multivariate Cox regression analysis showed that hepatolithiasis and hepatitis B virus infection had no effect on the prognosis of ICC patients after surgery (all P>0.05). Conclusion:Compared to HBV infection, ICC patients with hepatolithiasis have a worse prognosis. Hepatolithiasis and HBV infection have no effect on the prognosis of ICC after radical resection.
10.MiRNA-103-3p promotes neural cell autophagy by activating Wnt/β-catenin signaling via targeting rab10 in a rat model of depression
Yeming ZHANG ; Yuanxiang ZHANG ; Xuebin SHEN ; Guodong WANG ; Lei ZHU
Journal of Southern Medical University 2024;44(7):1315-1326
Objective To explore the neuroprotective role of Rab10 gene in depression and the mechanism mediating its effect.Methods Forty-eight male SD rats were randomized into a control group and 3 chronic unpredictable mild stress(CUMS)groups(n=12).The rats in the latter 3 groups were subjected to injections of normal saline,an adeno-associated viral(AAV)vector,or a Rab10-overexpressing AAV vector in the lateral ventricle after CUMS modeling.The depressive behavioral changes of the rats were assessed using behavioral tests.The TargetScan database was used to predict the miRNA interacting with Rab10 and the binding sites.The interaction between miRNA-103-3p and Rab10 was investigated using dual-luciferase and radioimmunoprecipitation(RIP)assay.The effect of corticosterone treatment on PC12 cell viability was assessed with CCK-8 assay.In corticosterone-stimulated PC12 cells,the changes in BDNF,CREB,p62,Beclin-1,Wnt3a,Gsk3β,phosphorylated(p)-Gsk3β,and β-catenin protein expressions following transfection with the Rab10-overexpressing AAV vector and a miRNA-103-3p inhibitor,alone or in combination,were analyzed using qRT-PCR and Western blotting.Results Injection of Rab10-overexpressing AVV vector into the lateral ventricle significantly improved depressive behaviors of CUMS rats.The mRNA and proteins expression of Rab10 were significantly down-regulated in the hippocampus of CUMS rats and in corticosterone-stimulated PC12 cells.Bioinformatics analysis and the results of double luciferase and RIP experiments confirmed the targeting relationship between miRNA-103-3p and Rab10.In PC12 cells,overexpression of Rab10 or silencing miRNA-103-3p activated the Wnt/β-catenin signaling pathway,up-regulated the expressions of BDNF,CREB and Beclin-1,and down-regulated the expression of p62 protein;silencing Rab10 obviously blocked the effect of miRNA-103-3p inhibitor.Conclusion In mouse models of depression,miRNA-103-3p activates Wnt/β-catenin signaling via targeting rab10 to improve neural plasticity and promotes neural cell autophagy.

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