1.Molecular Mechanism of Liuwei Dihuangwan Regulating GPNMB Expression and Enhancing Autophagy in Prevention and Treatment of Alzheimer's Disease
Yuxi LIU ; Zhongkang ZHU ; Songnan WANG ; Jiali LIU ; Ye YIN ; Jiarui MIAO ; Shunuo HE ; Danyu ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):1-10
ObjectiveThis study aims to investigate the effect of Liuwei Dihuangwan on the autophagy function in the hippocampus of senescence-accelerated mouse prone 8 (SAMP8) by regulating the expression of glycoprotein non-metastatic melanoma protein B (GPNMB). Furthermore, it is designed to explore the mechanism of the method of tonifying the kidneys and replenishing essence in the treatment of Alzheimer's disease (AD). MethodsIn experiment 1, 24 5-month-old SAMP8 mice were randomly and equally divided into the model group, and the low-, middle- and high-dose(0.59,1.18,2.36 g·kg-1) Liuwei Dihuangwan groups. At the same time, six 5-month-old senescence accelerated mouse resistant 1 (SAMR1) mice were used as the control group. The learning and memory ability was evaluated through novel object recognition experiment. Serum cortisol (Cort), adrenocorticotropic hormone (ACTH) and urine 17-hydroxycorticosteroid (17-OHCS) levels were detected by enzyme-linked immunosorbent assay (ELISA). The ultrastructure of hippocampal neurons was observed by transmission electron microscope (TEM), and the expression levels of hippocampal GPNMB, a disintegrin and metalloproteinase 10 (ADAM10) and autophagy-related proteins were detected by Western blot. In experiment 2, 18 SAMP8 mice were randomly and equally divided into the model group, vector control group (Vector), and GPNMB overexpression group (GPNMBOE). Lentiviral vectors were stereotactically injected into the brain (2 μL per side in the GPNMBOE group). Western blot was used to detect the expression of the above target proteins in the hippocampus; In Experiment 3, 24 SAMP8 mice were randomly and equally divided into the model group, Liuwei Dihuangwan group, Liuwei Dihuangwan+negative control (NC) group, and Liuwei Dihuangwan+GPNMB silencing group (shGPNMB). Before drug treatment, the Liuwei Dihuangwan+NC group and the Liuwei Dihuangwan+shGPNMB group were injected with negative control and GPNMB silencing lentivirus, respectively. Western blot was used to detect the expression of the above target proteins in the hippocampus. ResultsThe novel object discrimination index of mice in the model group was significantly lower than that of mice in the control group (P<0.01). The novel object discrimination index of mice in the medium- and high-dose Liuwei Dihuangwan groups was significantly higher than that of mice in the model group (P<0.01). Aggregated autolysosomes were observed in the normal hippocampus tissue by TEM. In the model group, mitochondria were dominant, and no typical characteristic autophagosomes were observed. In the low- and medium-dose Liuwei Dihuangwan groups, a small number of autolysosomes and autophagosomes with double-membrane structures were observed. In the high-dose Liuwei Dihuangwan group, the number of autophagosomes and autolysosomes was greater than that in the low- and medium-dose groups. The results of ELISA and Western blot showed that compared with the control group, the levels of serum Cort, ACTH, and urine 17-OHCS in the model group were substantially increased, while the expression of hippocampal ADAM10, Beclin1, and microtubule associated-protein light chain 3-Ⅱ/Ⅰ (LC3 Ⅱ/Ⅰ) was significantly decreased. The expression of GPNMB and ubiquitin binding protein p62 was significantly increased (P<0.05, P<0.01). Compared with the model group, the serum Cort and ACTH levels in the low-, medium-, and high-dose Liuwei Dihuangwan groups were significantly reduced, while only the urine 17-OHCS level in the high-dose group was significantly reduced. The hippocampal GPNMB, ADAM10, Beclin1, and LC3 Ⅱ/Ⅰ expression levels in the medium-, and high-dose groups of Liuwei Dihuangwan were significantly increased compared to the model group, whereas the expression of p62 was significantly reduced (P<0.01). The above indicators showed a progressive trend among the three groups. Compared with the model group, the GPNMBOE group showed a significant increase in GPNMB, ADAM10, Beclin1, LC3 Ⅱ/Ⅰ expression, and a significant decrease in p62 expression (P<0.01). Compared with the model group, the expression of GPNMB, ADAM10, Beclin1, and LC3 Ⅱ/Ⅰ in the hippocampus of the Liuwei Dihuangwan group significantly increased, while the expression of p62 significantly decreased (P<0.01). Compared with the Liuwei Dihuangwan group, the Liuwei Dihuangwan+shGPNMB group showed a significant decrease in GPNMB, ADAM10, Beclin1, LC3 Ⅱ/Ⅰ, and a significant increase in p62 expression (P<0.01). ConclusionLiuwei Dihuangwan can enhance hippocampal autophagy function and improve AD by upregulating GPNMB expression.
2.Association of sleep and screen time with coexistence of screening myopia and depressive symptom among primary and secondary school students
ZHAI Shuang, MIAO Shenghao, SHI Mengxing, ZHANG Yang, QI Jiarui, LI Jiaan, CHENG Pei, ZHANG Juan
Chinese Journal of School Health 2025;46(11):1640-1644
Objective:
To explore the prevalence of screening myopia and depressive symptom among primary and secondary school students in Xuzhou, and to explore the association of sleep and screen time on the coexistence of screening myopia and depressive symptom, so as to provide scientific references for developing intervention strategies to address the development of myopia and promote mental health in children and adolescents.
Methods:
From September to October 2024, a stratified cluster random sampling method was used to select 6 605 students in grade 4 to 12 in 2 urban and 2 suburban districts in Xuzhou. The students health condition and influencing factors questionnaire were used to assess students basic information, sleep time, and screen time. The Center for Epidemiological Studies Depression Scale (CES-D) was used to assess primary and secondary school students depressive symptom.Unaided distance visual acuity examination was conducted, and refractive assessment was performed using an automated refractometer without cycloplegic agents. The Chi-square test and multiple Logistic regression analysis were used to evaluate the association of sleep and screen time with the coexistence of screening myopia and depressive symptom.
Results:
The detection rates of screening myopia, depressive symptom, and screening myopia and depressive symptoms co morbidity among primary and secondary school students in Xuzhou were 60.35%, 4.45% and 18.61% respectively. Results from the multinomial Logistic regression analysis, using the healthy group as the reference and after adjusting for confounding factors, showed that students with insufficient sleep duration were more likely to have depressive symptom ( OR=1.57, 95%CI =1.08-2.27) and the coexistence of screening myopia and depressive symptom ( OR=1.85, 95%CI =1.45-2.36). Students with daily screen time≥2 h were more likely to have depressive symptom only ( OR=1.41, 95%CI =1.04-1.93) and the coexistence of screening myopia and depressive symptom ( OR=1.31, 95%CI =1.06-1.61). Further stratified analysis based on sufficient and insufficient sleep duration revealed that only in the insufficient sleep duration group, students with daily screen time≥2 h had an increased risk of depressive symptom only ( OR=1.49, 95%CI =1.07-2.07) and the coexistence of screening positive myopia and depressive symptom ( OR=1.40, 95%CI =1.11- 1.77 ) (all P <0.05).
Conclusions
Primary and secondary school students with insufficient sleep duration and daily screen time≥2 h have higher risks of depressive symptoms and the coexistence of screening myopia and depressive symptoms. It is recommended to ensure adequate sleep duration and limit screen time for children and adolescents.
3.Development status among infants at ages of 0 to 36 months in Xiaoshan District
LI Qing ; ZHONG Bihua ; SUN Jiarui ; DAI Fengpo ; DING Yina ; MIAO Xiangqing ; FU Yaxian ; TU Yuyan ; TAN Wenjuan ; YU Yinfei
Journal of Preventive Medicine 2024;36(3):255-259
Objective:
To learn the status and influencing factors of development among infants at ages of 0 to 36 months in Xiaoshan District, Hangzhou City, so as to provide the reference for promoting healthy development of infants.
Methods:
Infants at ages of 0-36 months who underwent physical examination in Child Health Clinic of Xiaoshan District Community Health Service Center were selected in 2022. General data of infants and their mothers were collected through questionnaires, and the development status of infants was screened by Age and Stages Questionnaire (third edition). Factors affecting the development status were identified using a multivariable logistic regression model.
Results:
A total of 2 519 infants were investigated, including 1 339 males (53.16%) and 1 180 females (46.84%). There were 608 infants with abnormal development of at least one functional area of communication (CM), gross motor (GM), fine motor (FM), problems solving (CG) and personal-social (PS). The abnormal rate was 24.14%, and the abnormal rates of the above functional areas were 9.77%, 6.59%, 7.98%, 6.39% and 9.33%, respectively. Multivariable logistic regression analysis showed that gender (male, OR=1.563, 95%CI: 1.191-2.052), mother's childbearing age (≥35 years, OR=1.411, 95%CI: 1.001-1.988), mother's educational level (lower than junior college, OR=1.460, 95%CI: 1.116-1.912) were factors affecting abnormal development of CM; preterm birth (OR=2.323, 95%CI: 1.315-4.103) was factors affecting abnormal development of GM; gender (male, OR=1.654, 95%CI: 1.225-2.232) was factors affecting abnormal development of FM; gender (male, OR=1.511, 95%CI: 1.086-2.102) and mode of delivery (cesarean section, OR=1.460, 95%CI: 1.060-2.010) were factors affecting abnormal development of CG; gender (male, OR=1.340, 95%CI: 1.019-1.763) and birth weight (low birth weight, OR=1.985, 95%CI: 1.149-3.432) were factors affecting abnormal development of PS.
Conclusions
The rate of abnormal development among infants at ages of 0 to 36 months in Xiaoshan District is 24.14%. Gender, preterm birth, mode of delivery, birth weight, mother's childbearing age and mother's educational level could affect the development status of infants.
4.The role of circadian clock-controlled mitochondrial dynamics in nonalcoholic fatty liver disease
Ce ZHANG ; Jiarui MIAO ; Xu FAN
Journal of Clinical Hepatology 2024;40(8):1670-1676
Nonalcoholic fatty liver disease(NAFLD)is a disease closely associated with metabolic abnormalities and is currently one of the most common chronic liver diseases.Mitochondria are highly dynamic organelles involved in a variety of metabolic and bioenergetic pathways in the liver,and they respond to environmental changes in a highly dynamic manner through mitochondrial dynamics.The circadian clock is able to modulate mitochondrial dynamics,making it exhibit rhythmic changes.In case of circadian rhythm disorders,mitochondrial dynamics loses rhythmicity,and mitochondria are unable to respond to changing energy demands in different environments,leading to the development and progression of NAFLD.This article summarizes the important role of circadian clock-controlled mitochondrial dynamics in the etiology of NAFLD.
5.Resting-state functional MRI observation on relationship between functional connectivity of frontoparietal network and cognitive function in patients with cerebral small vessel disease
Ting LEI ; Wei YAN ; Siwei TANG ; Huiling ZHOU ; Haiqing LI ; Yuxing JIANG ; Xi HE ; Miao HE ; Jiarui SONG ; Lijing ZHOU ; Yajun LI ; Li CHEN
Chinese Journal of Medical Imaging Technology 2024;40(5):718-723
Objective To observe the relationship between functional connectivity(FC)of frontoparietal network(FPN)and cognitive function in patients with cerebral small vessel disease(CSVD)using resting-state functional MRI(rs-fMRI).Methods rs-fMRI of 50 CSVD patients with cognitive impairment(CI group),65 CSVD patients with normal cognition(NC group)and 60 healthy controls(HC group),as well as outcomes of neuropsychological tests were retrospectively analyzed.Brain regions with different FC of FPN were compared among 3 groups and between each 2 groups.Partial correlation analysis was used to evaluate the correlations of FC of brain regions value being statistically different between CI and NC groups and cognitive scores.Results Significant differences of FC in bilateral cingulate gyrus,left middle frontal gyrus,right supramarginal gyrus,right inferior parietal lobule and right medial superior frontal gyrus were found among groups(FWE correction,all P<0.05).Compared with NC group,FC of left cingulate gyrus decreased,of right inferior frontal gyrus and right medial superior frontal gyrus increased in CI group(FWE correction,all P<0.05).The decreased FC value of left cingulate gyrus was negatively correlated with clock drawing test score in CSVD patients(r=-0.159,P=0.049).Conclusion CSVD patients with or without CI had extensive abnormal FC of FPN,and the left cingulate gyrus was associated with patient's cognitive function.
6.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
7.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
8.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
9.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
10.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.


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