1.Effect of Bushen Huoxue Granule (补肾活血颗粒) on Dopamine Homeostasis and ERK/CREB/VMAT2 Signaling Pathways in the Striatum in Parkinson's Disease Model Mice
Hehao SUN ; Yingfan CHEN ; Peng WANG ; Xiaohan GENG ; Yuzhi ZHANG ; Qian ZHANG ; Min LI ; Shaodan LI ; Minghui YANG
Journal of Traditional Chinese Medicine 2025;66(23):2484-2493
ObjectiveTo investigate the possible mechanism of Bushen Huoxue Granule (补肾活血颗粒, BHG) in treating Parkinson's disease (PD) from the perspecitve of dopamine (DA) homeostasis. MethodsSeventy-two mice were randomly divided into blank group, model group, madopar group and BHG low-, medium- and high-dose groups, with 12 mice in each group. Except for the blank group, all mice were administered intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to induce a PD model. On the day following the injection, BHG low-, medium- and high-dose groups were administered BHG at doses of 1.25, 2.5, and 5.0 mg/(g·d) by oral gavage, respectively, while the madopar group received madopar tablets at dose of 0.093 8 mg/(g·d) by oral gavage. The blank group and the model group were given 0.2 ml/10 g of distilled water by gavage. All treatments were given once daily for 14 days. Open field test, pole climbing test and grip test were used to evaluate the behavior of mice in each group. Immunohistochemistry was used to detect the expression of tyrosine hydroxylase (TH) in striatum. Nissl staining was used to detect the activity of striatal neurons. The contents of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in striatum were detected by ultra performance liquid chromatography tandem mass spectrometry. The number and volume of synaptic vesicles were observed by transmission electron microscope. The expression of vesicular monoamine transporter 2 (VMAT2) in striatum was detected by immunofluorescence. Western Blot was used to detect the expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), cAMP response element-binding protein (CREB), phosphorylated CREB (p-CREB) and VMAT2 in striatum. ResultsCompared to the blank group, mice in the model group showed a significant decline in total distance and average speed in the open field test, along with an increase in total resting time; in the pole test, both the time required for the mice to turn completely downward (T-turn) and the total time taken to reach the bottom of the pole (T-total) were prolonged; forelimb grip strength was reduced; in the striatum, the mean optical density of TH, the average fluorescence intensity of VMAT2 protein, and DA content all decreased, while the number of striatal neurons was reduced, and the DOPAC/DA ratio was elevated; the levels of p-ERK/ERK, p-CREB/CREB, and VMAT2 in the striatum significantly decreased (P<0.01); transmission electron microscopy revealed that both the number and volume of synaptic vesicles in striatal neurons were markedly reduced. Compared to the model group, mice in the madopar group and BHG low-, medium- and high-dose groups showed significant improvements in all the above indicators (P<0.05 or P<0.01). Compared to madopar group, the BHG high-dose group exhibited increased DA content and elevated p-CREB/CREB ratio in the striatum (P<0.05). Compared to the BHG low-dose group, the BHG high-dose group showed increased total distance and mean velocity, decreased total resting time, T-turn, and T-total, as well as enhanced forelimb grip strength; moreover, the average fluorescence intensity of VMAT2 protein, DA content, p-ERK/ERK, p-CREB/CREB, and VMAT2 levels in the striatum were all significantly elevated (P<0.05 or P<0.01). ConclusionBHG may restore DA homeostasis and alleviate the damage of dopaminergic neurons by regulating ERK/CREB/VMAT2 signaling pathway.
2.Correlation between plasma NT-proBNP level and postoperative outcomes in elderly and critically ill patients with hip fractures
Taijun LUO ; Wenchao ZHANG ; Rui XIAO ; Tao XU ; Geng WANG ; Minghui YANG
The Journal of Clinical Anesthesiology 2024;40(1):18-22
Objective To investigate the correlation between preoperative N-terminal pro-B-type natriuretic peptidogen(NT-proBNP)levels and early postoperative outcomes in elderly and critically ill pa-tients with hip fractures.Methods A total of 593 elderly and critically ill patients with hip fractures from January 2018 to April 2021 were selected,including 189 males and 404 females,aged≥65 years,BMI 12.0-35.5 kg/m2,ASA physical status Ⅱ-Ⅳ.General preoperative information,intraoperative and post-operative discharge outcomes of patients were retrospectively obtained by the electrical clinical medical record system or telephone follow-up.The receiver operator characteristic(ROC)curve of preoperative plas-ma NT-proBNP and postoperative 30-day death was plotted,and the corresponding optimal cut-off value was 1 765.0 pg/ml.According to NT-proBNP values,the patients were divided into two groups:low-ratio group(NT-proBNP≤1 765.0 pg/ml,group L,n = 463)and high-ratio group(NT-proBNP>1 765.0 pg/ml,group H,n = 130).The correlation between different plasma concentrations of NT-proBNP before surgery and ICU length of stay,total length of stay,postoperative complications,and 30-day mortality rate were an-alyzed using univariate and multivariate logistic regression analysis.Results Compared with group L,age,preoperative comorbidities with coronary heart disease,arrhythmia,chronic heart failure,lung disease,and chronic kidney disease,as well as mortality within 30 days after surgery were significantly increased in group H(P<0.05).The multivariate logistic regression analysis showed that high preoperative plasma NT-proBNP concentration was positive correlation with postoperative ICU length of stay(OR = 1.215,95%CI 1.073-1.375,P = 0.020)and 30-day mortality rate(OR = 32.696,95%CI 7.158-149.338,P<0.001).Conclusion High preoperative plasma NT-proBNP concentration is positive correlation with postoperative ICU hospitalization timeand 30-day mortality.
3.Application of chemogenetic technology in the study of neural circuits in depression
Shaowei LI ; Jiehui LI ; Mingkuan ZHANG ; Hao ZHANG ; Minghui HU ; Dan CHEN ; Kaiyong XU ; Zifa LI ; Xiwen GENG ; Sheng WEI
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(6):554-559
Chemogenetic technology is a receptor-ligand system that regulates cell viability and function by changing receptor specificity and affinity, and it achieves precise neuronal regulation by specifically regulating neurons and neural circuits. At present, this technique is widely used in the study of neural circuits. This article briefly describes the application and progress of chemogenetic technology in the study of depression neural circuits, reviews the application of chemogenetic technology in several brain regions closely related to depression, such as ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus and lateral habenula, and discusses the potential and challenges of chemogenetic technology as a technology for precise regulation of neural activity in future research, in order to provide reliable ideas and directions for chemogenetic technology in the study of depression neural circuits.
4.Application of neurocircuit identification technology in traditional Chinese medicine brain science
Yaru CUI ; Qian GAO ; Zifa LI ; Minghui HU ; Hao ZHANG ; Xiwen GENG ; Xinyu WANG ; Sheng WEI
Acta Laboratorium Animalis Scientia Sinica 2024;32(8):1059-1064
The neural circuit is the material carrier for the realization of brain function,consisting of a complex network of different neurons.Neural circuit identification technology tracks the structure and activity of specific neural circuits,to study their adequacy and necessity for brain function,which is crucial for understanding the pathogenesis of brain diseases.As a high-tech tool in the fields of neuroscience and brain science,neural circuit identification technology has been gradually introduced into basic traditional Chinese medicine(TCM)research in recent years.This systematic review considers the principles of neural circuit identification technology and progress in its application in the field of TCM neuroscience.We note that future developments in this field should be based on the overall concept of TCM characteristics and the design of syndrome differentiation and treatment.Further research on the neural circuit mechanisms of diverse method of TCM in diseases will help to promote the deep integration of TCM and modern neuroscience.
5.Confusion and countermeasures of the non-conditioned anxiety test in rodent laboratory animals
Kun LIU ; Ying XING ; Zhiyong ZHENG ; Jialing XU ; Hao ZHANG ; Minghui HU ; Xiaohua HE ; Kai CHEN ; Zifa LI ; Xiwen GENG ; Sheng WEI
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(4):361-366
Anxiety is a major mood disorder, and the high morbidity, co-morbidity and disability of anxiety disorders seriously affect people's quality of life, so the importance and urgency of research on anxiety cannot be overstated. Animal models are the main carriers for studying the mechanism of disease occurrence and development, drug efficacy evaluation and drug development.Unconditioned anxiety model is a common anxiety model.Elevated plus maze test, open field test and light-dark box test are widely accepted paradigms for the detection of unconditioned anxiety.This kind of behavioral paradigm based on environmental exposure takes advantage of the conflict between curiosity and fear of the unfamiliar environment to simulate and detect the anxiety of animals.However, the validity of these behavioral paradigms for evaluating anxiety in animals is questionable.In this paper, we discuss the concept of anxiety, the definition of anxiety behavior in the behavioral test of unconditioned anxiety, and the factors to be considered in the test of unconditioned anxiety behavior.On this basis, new solutions were proposed to the contradictions and blind spots in order to improve the test paradigm of anxiety behavior and provide a more reliable animal model for the evaluation of anxiety.This paper presents a new approach to address the contradictions and blind spots of this paradigm.
6.The past,present,and future of in vivo-implant-able recording microelectrodes:the neural interfaces
Kun LIU ; Hao ZHANG ; Minghui HU ; Zifa LI ; Kaiyong XU ; Dan CHEN ; Wenqiang CUI ; Cui LYU ; Ran DING ; Xiwen GENG ; Sheng WEI
Chinese Journal of Pharmacology and Toxicology 2023;37(7):553-553
Neural recording electrodes enable the acquisition and collection of electrical signals from neu-rons,and these recorded neural electrical signals are an important means of understanding neuronal activity.As a major component of the brain-machine interface,neu-ral recording electrodes serve as a bridge between the nervous system and external devices.The extracted information can be used to understand the state of the brain and acts as a feedback signal to regulate external devices,thus providing important information for the clini-cal treatment of neurological diseases.Moreover,the electrodes can be used as a vehicle for drug injection to directly treat diseases.Since the time that Strumwas-ser used microwires to achieve long-term recordings of neural activity in hibernating squirrels,implantable elec-trode technology has gradually improved over three gen-erations of development,and progress has been made in improving the biocompatibility,mechanical performance(size,shape,density,etc.),and signal-to-noise ratio.Implantable neural recording electrodes can acquire sig-nals from cortical and deep neural clusters,with the advantages of high signal-to-noise ratio,information con-tent,and spatial/temporal resolution.However,there is still a need to improve the structure and performance of these electrodes;for example,their high invasiveness and lack of biocompatibility pose technical difficulties in the process of translation to the clinic.This paper reviews the basic requirements for electrodes,main recording methods and signal types,common types of implant-able neural recording electrodes,and their challenges and future development directions.With the continuous development of electrode materials,equipment,systems,and neurotechnology,it should be possible to apply neu-ral recording electrodes in clinical practice,to promote safe and efficient treatment of human diseases.
7.Safety of early hip fracture surgery for elderly patients on clopidogrel
Minghui YANG ; Dongchen YAO ; Yan ZHOU ; Wenchao ZHANG ; Geng WANG ; Ping ZHANG ; Shiwen ZHU ; Xinbao WU
Chinese Journal of Orthopaedic Trauma 2021;23(3):197-201
Objective:To investigate the safety of early hip fracture surgery for elderly patients on clopidogrel.Methods:This retrospective study included 242 consecutive elderly patients (≥65 years) with acute hip fracture who had undergone surgery at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital between November 2016 and April 2017. Of them, 20 were assigned into the study group who had taken clopidogrel before injury but discontinued its use within 4 days before surgery. They were 6 males and 14 females, with a median age of 80 years (77, 81). Their operation procedures for hip fracture included internal fixation with cannulated screws for femoral neck fracture in 2 cases, hemiarthroplasty for displaced femoral neck fracture in 11 cases, and internal fixation for intertrochanteric fracture in 7 cases. The control group included 222 patients who had undergone the same operative procedures but not taken any antiplatelet or anticoagulant drugs. The 2 groups were compared in terms of time between admission and operation, operation duration, intraoperative blood loss, perioperative transfusion and complications related to bleeding to analyze the safety of early surgery.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). There was no significant difference between the 2 groups in the time between admission and operation [42.5 (36.3, 48.0) h for the study group versus 43.0 (28.0, 61.0) h for the control group] ( P=0.870). The median time between the last use of clopidogrel and operation was 55.0 (30.5, 71.0) h. There were no significant differences between the 2 groups in preoperative hemoglobin, operation duration, intraoperative blood loss, rate or amount of perioperative blood transfusion, or rate or amount of wound drainage ( P>0.05). The rate of general anesthesia was significantly higher for the study group (45.0%, 9/20) than for the control group (18.5%,41/222) ( P=0.012). No complications related to spinal hematoma occurred in the patients receiving spinal anesthesia from the study group. Wound hematoma and subsequent infection occurred in 2 patients from the control group. Conclusion:Early hip fracture surgery is safe for elderly patients on clopidogrel.
8.The predictive value of serum alkaline phosphatase combined with parathyroid hormone in all-cause and cardiovascular mortality in maintenance hemodialysis patients
Xiaohan LU ; Haixia LIN ; Minghui GENG ; Xiaoyan WU ; Ping GAO
Chinese Journal of Internal Medicine 2020;59(8):634-637
To analyze the predictive value of serum intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) on all-cause and cardiovascular mortality in maintaining hemodialysis (MHD) patients. A total of 224 MHD patients were prospectively investigated and followed up for 2 years. Serum iPTH levels were not associated with all-cause death and cardiovascular death ( HR=1.001, 95% CI 1.000-1.004, P=0.048) . The level of serum ALP was associated with cardiovascular death ( HR=1.002, 95% CI 1.000-1.004, P=0.033) . ALP≥106 IU/L was an independent risk factor for cardiovascular death in MHD patients ( P<0.05) . The joint variable was correlated with mortality in MHD patients ( HR=1.002, 95% CI 1.000~1.004, P=0.033) , that equal or over 37.28 was an independent risk factor for mortality ( P<0.05).
9.Diagnostic value of high frequency ultrasound on lesions of knee traumas
Ping XU ; Minghui TONG ; Hongxia LU ; Jieyan WU ; Xilin GENG
Chinese Journal of Ultrasonography 2011;20(5):417-419
Objective To discuss the diagnostic value of high frequency ultrasound on lesions of knee traumas.Methods Ninty-eight cases with post-traumatic knee injuries were examined by high frequency ultrasound,and the characteristics of changing ultrasonogram were observed and comparing with surgical results and MR.Results Of the 98 cases with post-traumatic knee injuries,there were 57 cases with effusion and hematocele in knee joint,among which there were 41 cases with collateral ligaments and meniscus injuries,the diagnostic coincidence rate was 93.3% in tendon tear and complete tendon fracture(compared with MR),91.7% in partial and complete muscle tear(compared with MR),67.7% and 71.4% in collateral ligaments and meniscus injuries(compared with surgical results).Conclusions High frequency ultrasound can be used as a conventional imaging examination method for post-traumatic knee injuries.
10.The relationship between antiendothelial cell antibodies and anticardiolipin antibodies
Hui GENG ; Youkang ZHANG ; Minghui ZHAO
Chinese Journal of Nephrology 1997;0(05):-
Objective To investigate the relationship between antiendothelial cell antibodies(AECA)and anticardiolipin antibodies(ACA)in patients with lupus nephritis. Methods 58 sera from patients with lupus nephritis were studied. ELISA technique were used to detect both AECA and ACA, and immunoblotting was performed to determine specific endothelial targets. Results The prevalence of IgG-AECA and IgG-ACA positive were 36.2% and 39.7% respectively in the patients with lupus nephritis. 17 out of 23 patients with ACA had higher titers of AECA, while only 4 out of 35 patients without ACA were AECA positive(P

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