1.Alpha-synuclein Fibrils Inhibit Activation of the BDNF/ERK Signaling Loop in the mPFC to Induce Parkinson's Disease-like Alterations with Depression.
Zhuoran MA ; Yan XU ; Piaopiao LIAN ; Yi WU ; Ke LIU ; Zhaoyuan ZHANG ; Zhicheng TANG ; Xiaoman YANG ; Xuebing CAO
Neuroscience Bulletin 2025;41(6):951-969
Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals
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Brain-Derived Neurotrophic Factor/metabolism*
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alpha-Synuclein/metabolism*
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Male
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Prefrontal Cortex/drug effects*
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Rats, Sprague-Dawley
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Depression/metabolism*
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MAP Kinase Signaling System/drug effects*
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Rats
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Parkinson Disease/metabolism*
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Receptor, trkB/metabolism*
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Phosphorylation
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Disease Models, Animal
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Signal Transduction
2.Impact of SALL4 gene promoter methylation on trophoblast cell function
Mengxia XIE ; Zhaoyuan YANG ; Keji LI ; Jicong LU ; Shuangyu ZHANG ; Jing GUO ; Da XU ; Kanglu YAN ; Ning HAN ; Yuehua LIU
Chinese Journal of Perinatal Medicine 2025;28(5):395-402
Objective:To investigate the expression and methylation status of the SALL4 gene in placental tissues of fetal growth restriction (FGR) and its effects on trophoblast cell proliferation, migration, and invasion. Methods:Placental tissues were collected from 20 full-term FGR patients and 20 healthy term controls who underwent regular prenatal examination and cesarean section at the Third Affiliated Hospital, Zhengzhou University between July 2023 and February 2024. SALL4 mRNA and protein expression were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Methylation specific polymerase china reaction (MSP) assessed promoter methylation levels. HTR8/SVneo cells were transfected with SALL4-targeting small interfering RNA (si-SALL4) or negative control small interfering RNA (si-NC). HTR8/SVneo cells were treated with the demethylating agent 5-aza-2′-deoxycytidine (5-Aza-dC) to inhibit gene methylation (5-Aza-dC group) or with 10% RPMI-1640 medium as a vehicle control. Transfection efficiency (for siRNA) and the efficacy of 5-Aza-dC-induced demethylation were assessed by qRT-PCR and Western blot. The functional effects of SALL4 knockdown and methylation inhibition on trophoblast cells were evaluated using proliferation assays, scratch wound healing assays, and Transwell invasion assays. Statistical analyses included independent t-tests and Chi-square test. Results:(1) Human tissues: FGR placentas showed lower SALL4 mRNA (0.802±0.194 vs. 1.015±0.186, t=3.55) and protein expression (0.445±0.114 vs. 0.701±0.113, t=3.19), alongside higher methylation rates of SALL4 [80% (16/20) vs. 15% (3/20), χ2=14.44] compared to controls (all P<0.05). (2) In vitro: si-SALL4 transfection reduced HTR8/SVneo proliferation (OD450 at 48 h: 0.653±0.021 vs. 0.827±0.040, t=6.60), migration [healing rate at 48 h: (24.317±2.637)% vs. (49.327±1.961)%, t=13.18], and invasion [counted invaded cells: (133.000±6.557) vs. (272.667±18.009) cells, t=12.62] versus si-NC (all P<0.05). Conversely, 5-Aza-dC treatment increased HTR8/SVneo proliferation (0.917±0.042 vs. 0.783±0.031, t=-4.47), migration [(71.097±3.354)% vs. (51.632±2.877)%, t=-7.63], and invasion [(384.000±12.166) vs. (202.833±7.095) cells, t=-13.69] versus vehicle control (all P<0.05). Conclusions:Hypermethylation of the SALL4 promoter in FGR placentas suppresses its expression, impairing trophoblast cell function. Demethylation restores SALL4 expression and enhances cellular proliferation, migration, and invasion, involving in the occurrence and development of FGR disease.
3.Relationship between school bullying and non-suicidal self-injury behaviors in adolescents with depressive disorders: the pathways of self-esteem and alexithymia
Liping LIU ; Min ZHANG ; Yingyi CHEN ; Binglan XU ; Lei DU ; Zhaoyuan XU
Sichuan Mental Health 2025;38(4):327-332
BackgroundNon-suicidal self-injury (NSSI) behaviors are common among adolescents with depressive disorders, and school bullying is recognized as a major risk factor. Previous research has shown that self-esteem and alexithymia are closely associated with both school bullying and NSSI. However, the mediating roles of self-esteem and alexithymia in the link between school bullying and NSSI are unclear. ObjectiveTo explore the mediating roles of alexithymia and self-esteem in the relationship between school bullying and NSSI behaviors in adolescents with depressive disorders, in order to inform intervention strategies targeting NSSI in this population. MethodsA total of 335 adolescents diagnosed with depressive disorders and treated at the First Psychiatric Hospital of Harbin from July 2023 to October 2024 were enrolled. Assessments included a self-developed demographic questionnaire, Adolescent Non-suicidal Self-injury Assessment Questionnaire-Behavior (ANSAQ-B), Delaware Bullying Victimization Scale-Student (DBVS-S), Rosenberg Self-Esteem Scale (RSES), and 26-item Toronto Alexithymia Scale (TAS-26). Pearson correlation analysis was used to examine the relationship among variables. Controlling for gender and age at onset of depressive symptoms, mediation analysis was performed using the “mediation” package in R 4.4.2. ResultsScores on DBVS-S and TAS-26 were positively correlated with ANSAQ-B score (r=0.408, 0.417, P<0.01), while RSES scores were negatively correlated(r=-0.300, P<0.01). Regression analysis showed that school bullying and alexithymia significantly positively predicted NSSI behaviors (B=0.212, 0.333, P<0.01), while self-esteem negatively predicted NSSI behaviors (B=-0.368, P<0.01). Alexithymia was found to mediate the relationship between school bullying and NSSI behaviors, with an indirect effect of 0.040 (95% CI: 0.018~0.069) ,account for 17.17% of the total effect. The indirect effect through self-esteem was not statistically significant (95% CI: -0.004~0.069). ConclusionExposure to school bullying and high levels of alexithymia are important predictors of NSSI behavior in adolescents with depressive disorders, and school bullying may indirectly influence NSSI behavior through alexithymia. [Funded by Scientific Research Project of Health Commition of Heilongjiang Province,(number, 20230303090154]
4.Advances in treatment strategies for drug-eluting stent restenosis of a new classification via optical coherence tomography
Yuan ZHANG ; Zhen FANG ; Jing ZHANG ; Bing XU ; Gan CAO ; Zhaoyuan ZHANG ; Jun JI
Journal of Clinical Medicine in Practice 2025;29(19):140-144,148
Catheter-based percutaneous coronary intervention has become a crucial approach for treating obstructive coronary artery disease and is widely applied in clinical practice.Although the new generation of drug-eluting stents(DES)has significantly reduced the incidence of post-procedur-al restenosis and improved long-term clinical outcomes,in-stent restenosis(ISR)remains one of the key challenges affecting the long-term efficacy of percutaneous coronary intervention.Recent studies have demonstrated that DES still have certain inherent limitations.From the metallic stent platform,drug coating to the polymer carrier,each component may exert varying degrees of biological effects on the vascular intima.Optical coherence tomography(OCT),as a high-resolution intravascular imaging technique,has shown significant value in the mechanism research,etiological diagnosis,and clinical classification of ISR.It can clearly identify the tissue composition and morphological characteristics of ISR,providing a precise basis for the formulation of individualized treatment strategies.This review aimed to systematically search the existing literature,comprehensively review the clinical and patho-logical features of ISR after DES implantation,focus on the OCT-based ISR classification system,and summarize the current treatment strategies and latest advances for ISR.
5.Exploration on the application of TCM in the whole life-cycle management of pediatric epilepsy
Zhaoyuan CHEN ; Xilian ZHANG ; Hanjiang CHEN ; Ruiben LI ; Han LI ; Yuling TIAN
International Journal of Traditional Chinese Medicine 2025;47(12):1652-1657
Epilepsy is a chronic neurological disorder that often begins in childhood and can extend over the entire life course; therefore, it is necessary to establish a long-term, systematic life-course management model. Whole life-cycle disease management emphasizes interventions at key points in time and focuses on diagnosis and treatment points at all stages of life and disease processes. Guided by the concept of holism and preventive treatment, this article discussed the application strategies of TCM in the prevention, control, treatment, health and management of epilepsy in children at different stages. In the prevention period, the disease should be prevented first, and early screening should be carried out; in the control period, the disease should be prevented from changing, and the early intervention of Chinese materia medica should be carried out; during the treatment period, the combination of disease and syndrome and dynamic syndrome differentiation by stages were adopted; during the rehabilitation period, the treatment of different diseases with the same treatment should be emphasized to manage the comorbidity and improve the prognosis; in the long-term management period, the prevention and recovery after stroke should be focused on, and the comprehensive management scheme of TCM in the transition period from children to adults should be put forward. This article systematically expounded the role of TCM in improving seizure control rate and prognosis in the whole life-cycle management of childhood epilepsy, and actively explored the construction of the whole process health management system of chronic diseases.
6.Clinical Observation on Acupuncture Combined with Western Medicine in the Treatment of Lumbar Disc Herniation of Qi Stagnation and Blood Stasis Type
Long CHEN ; Wanxia ZHANG ; Niandong LI ; Zhaoyuan ZHANG ; Zhouhang ZHENG ; Yu ZHANG ; Xuemeng XU
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(2):322-327
Objective To observe the clinical efficacy of acupuncture combined with western medicine in the treatment of lumbar disc herniation(LDH)of qistagnation and blood stasis type.Methods A total of 62 cases of patients with LDH of qistagnation and blood stasis type were randomly divided into observation group and control group,with 31 cases in each group.The control group was given conventional western medicine for treatment,and the observation group was treated by acupuncture on the basis of the control group,the course of treatment covered three consecutive weeks.After three weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Japanese Orthopedic Association(JOA)scores and Oswestry Disability Index(ODI)scores,as well as the Visual Analogue Scale(VAS)scores of pain,were observed before and after the treatment of the patients in the two groups.The changes in muscle tension,muscle hardness,and muscle elasticity of the multifidus muscle(MM)and lumbar multifidus muscle(LMM)before and after treatment were compared between the two groups.And the safety and the occurrence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate was 96.77%(30/31)in the observation group and 74.19%(23/31)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(2)After treatment,the VAS,JOA,and ODI scores of the patients in the two groups improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.01).(3)After treatment,the muscle tension,muscle hardness,and muscle elasticity of LMM and MM of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)The incidence rate of adverse reactions was 9.68%(3/31)in the observation group and 9.68%(3/31)in the control group;the intergroup comparison showed that there being no statistically significant difference(P>0.05).Conclusion Acupuncture combined with western medicine in the treatment of LDH of qistagnation and blood stasis type can significantly improve the lumbar function and clinical symptoms of the patients,and improve the muscular performance of the patients'LMM and MM,so as to enhance their quality of life.
7.Clinical Observation of Dangui Siwei Yin Cell-Wall Broken Powder in Treating Degenerative Lumbar Spinal Stenosis with Qi Deficiency and Blood Stasis Syndrome
Zhaoyuan ZHANG ; Long CHEN ; Zhouhang ZHENG ; Hua SHEN ; Miaoling LIU ; Yanling LIANG ; Weixuan CHEN ; Yu ZHANG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(11):2720-2727
Objective To evaluate the clinical efficacy of Dangui Siwei Yin cell-wall broken powder in the treatment of degenerative lumbar spinal stenosis(DLSS)with qi deficiency and blood stasis syndrome.Methods A randomized controlled trial was conducted on 72 patients with qi deficiency and blood stasis-typed DLSS admitted to Guangdong Second Traditional Chinese Medicine Hospital(Huangpu Hospital)from November 2023 to January 2025.Patients were randomly divided into a cell-wall broken powder group and a traditional midicinal slice group(36 cases each)using a random number table method.Both groups received conventional western treatment(oral administration of Etoricoxib Tablets and Mecobalamin Tablets).Additionally,the cell-wall broken powder group was treated with Dangui Siwei Yin cell-wall broken powder,while the traditional midicinal slice group received traditional decoction of Dangui Siwei Yin.Both groups underwent a 1-week treatment course.Changes in Visual Analogue Scale(VAS)of pain scores,Oswestry Disability Index(ODI)scores,and Japanese Orthopaedic Association(JOA)lumbar function scores were observed before and after treatment.Clinical efficacy and medication safety were evaluated.Results(1)After one week of treatment,the total effective rate was 88.89%(32/36)in the cell-wall broken powder group and 75.00%(27/36)in the traditional midicinal slice group.The intergroup comparison(by chi-square test)showed that the efficacy in the cell-wall broken powder group was superior to the traditional midicinal slice group(P<0.05).(2)After treatment,VAS and ODI scores were significantly decreased in both groups(P<0.05),while JOA scores significantly increased(P<0.05).The cell-wall broken powder group demonstrated superior improvements in VAS and ODI reduction and JOA elevation compared to the traditional midicinal slice group(P<0.05).(3)The adverse reaction rate was 8.33%(3/36)in the cell-wall broken powder group and 11.11%(4/36)in the traditional midicinal slice group,with no statistically significant difference(P>0.05).Conclusion Compared with traditional midicinal slice,Dangui Siwei Yin cell-wall broken powder exhibit better efficacy in alleviating low back and leg pain and improving lumbar function in qi deficiency and blood stasis-typed DLSS patients.This study provides evidence-based medical support for the clinical application and further development of cell-wall broken powder formulations in traditional Chinese medicine.
8.Development model and considerations for the immunology platform in research-oriented hospitals
Zhaoyuan LIANG ; Yang BAI ; Dan LIU ; Yanfang LI ; Liu YANG ; Lixiang XUE ; Jianling YANG ; Yuqing WANG ; Zhengyang GUO ; Jie ZHANG
Chinese Journal of Medical Science Research Management 2025;38(3):219-226
Objective:This study systematically summarized the construction experience of the immunology platform at the Institute of Basic Medical Sciences, Peking University Third Hospital, aiming to provide theoretical references and practical guidance for research-oriented hospitals in building high-quality research platforms.Methods:This study employed case study analysis to elaborate on the platform development initiatives, integrating literature analysis and in-depth interviews to conduct a horizontal comparison of management models among peer research platforms.Results:Through five years of development, the platform had achieved remarkable outcomes via a model integrating ″Talent cultivation-Technological innovation-Equipment procurement″ Research talents had demonstrated breakthroughs in securing national-level research grants, publishing high-impact papers, and obtaining scientific awards. The technical service system had achieved enhancement in both service scope and professional depth, fostering robust interdisciplinary synergy. The platform had effectively expanded its societal engagement capacity.Conclusions:The sustainable advancement of research-oriented hospital immunology platform necessitates establishing standardized flow cytometry databases and implementing high-dimensional data integration. Building upon multidisciplinary convergence, it is imperative to pioneer innovative operational mechanisms characterized by efficiency, open-access, and shared frameworks.
9.Correlation between systemic inflammatory response index and prognosis of elderly patients with heart failure
Jiling YU ; Zhaoyuan ZHANG ; Yifan DENG ; Zhen FANG ; Jun JI ; Shenghu HE ; Jing ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(4):450-453
Objective To explore the correlation between systemic inflammatory response index(SIRI)and the prognosis of elderly heart failure(HF)patients.Methods A retrospective study was conducted on 300 elderly HF patients with complete medical records hospitalized in our de-partment from January to December 2022.During the follow-up period for 1 year in different ways,46 of them were lost,and 254 were finally included.Baseline data,complete blood count at admission,and results of auxiliary examinations,and medicine adherence after discharge were col-lected and recorded.According to the occurrence of major adverse cardiovascular events(MACE),the subjected patients were divided into a MACE group(96 cases)and a non-MACE group(158 cases).The baseline data and relevant examination indicators were compared between the two groups,and the relevant factors for the occurrence were analyzed by using logistic regression.ROC curve analysis was employed to assess the predictive value of SIRI for MACE occurrence.Results The MACE group had significantly advanced age,larger proportion of diabetes mellitus,higher neutrophil and platelet counts,and elevated D-dimer level,but lower standardized medication rate when compared with the non-MACE group(P<0.05,P<0.01).The SIRI level was obviously higher in the MACE group than the non-MACE group[1.70(1.13,2.33)vs 1.29(0.85,2.06),P=0.002].Multivariate logistic regression analysis showed that atrial fibrillation,standardized medi-cation,mononuclear cells,and SIRI were independent risk factors for the occurrence of MACE in elderly HF patients(P<0.05,P<0.01).ROC curve analysis indicated that the AUC value of SIRI in predicting the occurrence of MACE was 0.614(95%CI:0.544-0.683),with a sensitivity of 0.813 and a specificity of 0.437.Conclusion SIRI is significantly correlated with the occurrence of MACE in elderly HF patients,and has a certain predictive value for their prognosis.
10.Design of Evidence-Based Decision-Making Pathway for the Selection of the National Essential Medicines List
Haili ZHANG ; Wenjie CAO ; Yijiu YANG ; Weili WANG ; Ning LIANG ; Ziteng HU ; Bin LIU ; Lijiao YAN ; Huizhen LI ; Zhaoyuan GONG ; Guozhen ZHAO ; Yanping WANG ; Nannan SHI
Chinese Health Economics 2025;44(1):15-19
The National Essential Medicines System could protect public health and ensure access to essential medications.Although the current selection methods for China's National Essential Medicines Lists(NEMLs)are becoming more scientific and standardized,there are still problems such as much emphasis on expert experience and the lack of transparency of decision-making basis.To address these issues,it proposes an evidence-based decision-making pathway for NEMLs selection guided by clinical value.This approach ensures a strong integration of evidence and decision-making,offering valuable insights for improving the adjustment procedures and selection criteria of the NEMLs in China.

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