BACKGROUND:The abuse of methamphetamine (METH) is associated with an increased risk of Parkinson's disease (PD), whereas microglial polarization and glucose metabolism disorders are closely related to the progression of PD. This study aimed to investigate the specific molecular mechanism underlying the promotion of PD progression by METH through the regulation of microglial polarization and glycolysis. METHODS:METH-induced C57BL/6 mice and BV2 cells were used to construct PD-like neurotoxicity animal and cell models for experimental investigation. Behavioral tests, immunohistochemistry and Nissl staining were used to assess the behavioral ability and neuronal damage of the animals. The levels of related proteins, inflammatory cytokines and glycolysis were detected using immunofluorescence, ELISA, Western blotting, and CCK-8 assays. RESULTS:METH treatment significantly promoted behavioral disorders in PD mice, reduced the number of TH-positive neurons, and aggravated neuronal damage in the substantia nigra (SN). In addition, METH decreased the M2 marker proteins Arg-1 and CD206 and increased the M1 marker proteins iNOS and CD86; the proinflammatory cytokines TNF-α, IL-β, and IL-6; and glucose uptake, glucose consumption and lactic acid production, thus promoting M1 polarization and glycolytic activity in BV2 cells. In terms of the underlying molecular mechanism, METH treatment significantly increased the level of LPA. METH promotes LPA expression via upregulation of LIPH expression, and activates the PI3K/AKT pathway. Knockdown of LIPH or treatment with BrP-LPA reduces the ability of METH to promote M1 microglial polarization and glycolytic activity. Furthermore, the addition of the PI3K/AKT signaling pathway activator 740 YP weakened the inhibitory effect of BrP-LPA on the above process. CONCLUSION:METH may promote M1 polarization and glycolytic activity in microglia by activating LIPH/LPA/PI3K/AKT signaling, thus promoting the progression of PD.

Parkinson’s disease (PD) constitutes the world’s second most widespread neurodegenerative ailment impacting the central nervous system. Its complex pathogenesis and significant heterogeneity restrict development of effective treatments, making reliable animal models indispensable for mechanistic studies and drug development. Caenorhabditis elegans ( C. elegans ) serves as a superior preclinical organism, attributed to its streamlined nervous architecture, human orthologous genes, abbreviated lifespan, and tractable genetic manipulation. Following PRISMA 2020 guidelines, this systematic review screened 1259 papers published between 2010 and 2026, retaining 50 qualified studies. This review outlines two primary approaches to establish C. elegans -based PD models: transgenic genetic strains and toxin-triggered models. We further elaborate three principal avenues for pharmaceutical investigation utilizing these platforms: restraining α‑synuclein aggregation alongside dopaminergic neuroprotection, balancing oxidative stress and sustaining mitochondrial integrity, and tuning metabolic and senescence-associated signaling cascades. This work offers a framework to dissect PD pathogenic mechanisms and expedite development of disease-modifying agents against PD.

BACKGROUND:Microglial autophagy is closely related to the development of Parkinson's disease (PD). The objective of this research was to investigate the effect of glycyrrhizin (Gly) combined with electroacupuncture (EA) on PD mice and its potential regulation of microglial autophagy. METHODS:A PD mouse model was constructed using the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), followed by the administration of Gly to PD mice and EA. The activation of BV2 cells was triggered by lipopolysaccharide (LPS). Western blotting, immunofluorescence, flow cytometry, Nissl staining, and immunohistochemistry were used to investigate the molecular mechanism that governs how microglial autophagy levels influence PD progression. RESULTS:Elevated levels of HMGB1 were observed in both patients with PD and PD mice. Gly inhibited HMGB1 expression and extracellular secretion by increasing SIRT1 activity and subsequently inhibit BV2 autophagy. EA inhibited the autophagy of microglia in PD mice by inhibiting the activation of TRPV1 and reducing the expression of HMGB1 in vivo. Gly combined with EA downregulated HMGB1 expression, inhibited microglial autophagy and improved the PD process, resulting in better effects than Gly or EA alone. CONCLUSION:Gly combined with EA can reduce the level of autophagy in microglia by downregulating HMGB1, thereby improving the PD process and providing a theoretical basis for the clinical treatment of PD.

BackgroundDeep brain stimulation is a primary surgical treatment for advanced Parkinson’s disease (PD). The globus pallidus interna (GPi) is a key target for this procedure. The posterior subthalamic area (PSA) serves as an effective target for tremor-dominant Parkinson’s disease. However, it is less commonly utilized in conventional DBS surgery compared to the subthalamic nucleus (STN) or the ventral intermediate nucleus (VIM). There is currently no clinical research on the combined DBS surgery targeting both the PSA and the GPi, which is why we have conducted this study.Case reportWe introduced a case of a patient with advanced PD. Due to the patient’s primary manifestations of right-sided tremor and left-sided rigidity, along with significant dyskinesia on the left side, DBS implantation was performed in the left hemisphere targeting the PSA and in the right hemisphere targeting the GPi. The patient’s UPDRS-III score decreased from 73 to 46 postoperatively, showing an improvement of approximately 36.99%, while the H-Y stage improved from stage 4 to 2.5, representing a 37.5% improvement. During the 6-months postoperative follow-up, the patient’s PD symptoms were effectively controlled, with no significant adverse effects.DiscussionWhen advanced PD patients present with asymmetric and variable motor symptoms, combined DBS stimulation targeting both the GPi and the PSA is a viable treatment option.

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide and severely affects the physical and mental health of patients. The protein arginine methyltransferase 5 (PRMT5) has been shown to be associated with neuronal degeneration in PD, but its specific mechanism of mediating PD remains unclear. The purpose of this study was to investigate the role of PRMT5 in PD and its potential mechanism. PD models in rats and MN9D cells were induced by 6-hydroxydopamine (6-OHDA). Key genes and proteins were identified through real-time quantitative polymerase chain reaction (RT‒qPCR), Western blotting, and immunofluorescence staining; apoptosis levels were measured using flow cytometry; autophagosome formation was observed via monodansylcadaverine (MDC) staining; and neuronal damage in PD rats was evaluated using hematoxylin‒eosin (H E) and Nissl staining. In this study, we found that PRMT5 levels were elevated in the peripheral blood of PD patients and in 6-OHDA-induced rat brain tissue and MN9D cells and that the expression of PRMT5 was positively correlated with the level of α-Syn. After PRMT5 was knocked down, α-Syn levels in PD rats decreased, neuronal damage was inhibited, and motor disorders improved. In addition, knockdown of PRMT5 promoted 6-OHDA-induced MN9D cell proliferation, inhibited apoptosis, and upregulated autophagy. Mechanistically, PRMT5 inhibits the activation of the Wnt/β-catenin signaling pathway through H3R8me2s modification to stabilize the expression of DKK1, thus inhibiting neuronal autophagy and promoting the development of PD. Our study suggests that PRMT5 may be a potential intervention target for improving PD progression.

Deep brain stimulation (DBS) is a common therapy for managing Parkinson’s disease (PD) in clinical practice. However, a complete understanding of its mode of action is still needed. DBS is believed to work primarily through electrical and neurochemical pathways. Furthermore, DBS has other mechanisms of action. This review explores the fundamental concepts and applications of DBS in treating PD, including its mechanisms, clinical implications, and recent research.

Parkinson's disease (PD) is a neurodegenerative disease that mainly manifests as cognitive decline and motor dysfunction, the treatment of which is still a major challenge in the clinical field. Acupuncture therapy has been shown in many studies to enhance the body's own immunity and disease resistance. This study mainly discusses the specific mechanism underlying electroacupuncture intervention in improving PD. Male C57BL/6 mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce a mouse PD model, and the chorea trembling control area of the head of PD mice was treated by electroacupuncture. Western blotting was used to detect the expression of related proteins in mouse pathological samples; TUNEL measured neuronal apoptosis levels; Nissl staining observed neuronal damage; immunofluorescence and immunohistochemistry were used to detect the expression of Iba-1, TH, and α-syn in substantia nigra denser (SN). The expression levels of oxidative stress factors and inflammatory factors were measured by kits. Flow cytometry measured mitochondrial membrane potential and Ca2+ levels. MPTP intraperitoneal injection induced an increase in inflammatory factors in PD mice and promoted the oxidative stress response, and the inflammatory response was alleviated after electroacupuncture treatment. Electroacupuncture intervention effectively alters the decrease in oxidative stress levels and alleviates neuronal damage in PD mice. Electroacupuncture improves mitochondrial dysfunction induced by MPTP in PD mice by activating the SIRT1/AMPK signaling pathway. We also confirmed that knocking down TRPC1 can inhibit the SIRT1/AMPK signaling pathway, weaken the Ca2+ content in mouse neuronal tissue, and promote cell apoptosis. Electroacupuncture improves neuronal damage and alleviates PD in mice through the TRPC1 and SIRT1/AMPK signaling pathways. In addition, electroacupuncture therapy can improve MPTP-induced mitochondrial dysfunction in PD mice and alleviate the PD process.

Background: Parkinson's disease (PD) is a common central neurodegenerative disease in middle-aged and elderly people. The progressive degeneration and death of dopaminergic neurons leads to insufficient dopamine (DA) neurotransmitters. Acupuncture and moxibustion can alleviate the aging of neurons. Therefore, studying the neuroprotective effects of electroacupuncture (EA) in PD mice is particularly important. Methods: Intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was used to establish a PD mouse model, and lipopolysaccharide (LPS) was used to induce microglia polarization. Western blotting, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), Nissl staining and immunohistochemistry were used to detect neuronal apoptosis and injury, alpha-syn expression and microglial accumulation in PD mice. In addition, the levels of inflammatory factors were determined using enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the Ca2+ content. The fluorescein isothiocyanate (FITC) labeling method was used to assess glucose uptake. A reagent kit was used to detect glucose and lactate levels. Results: MPTP induced the selective loss of DA neurons in the SN of mice, altered Ca2+ homeostasis, and induced an inflammatory response. In addition, maintaining Ca2+ homeostasis depends on the activity of transient receptor potential channel 1 (TRPC1). EA therapy promotes TRPC1 expression, which has a negative regulatory effect on sodium-glucose cotransporter 1 (SGLT1). Under the action of EA, TRPC1 protein expression increased, Ca2+ concentrations increased, and the effect of SGLT1 was inhibited, thereby facilitating glucose metabolism, blocking the activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, restraining M1 polarization of microglia, and alleviating the PD process. Conclusion: EA promotes TRPC1/Ca2+ pathway activation, inhibits SGLT1-mediated regulation of glucose metabolism and PI3K/AKT pathway activation, inhibits microglial M1 polarization, and alleviates PD.

This study aims to elucidate the role of miR-23b-3p in mesenchymal stem cell exosomes in regulating the Wnt signaling pathway to promote autophagy of neurons and alleviate Parkinson's disease (PD) symptoms. We generated rat and cellular PD models with 6-OHDA, treated them with mesenchymal stem cell exosomes rich in miR-23b-3p and determined the expression of α-syn and Wnt/β-catenin pathway and autophagy-related genes. In the plasma of PD patients, the levels of miR-23b-3p and the Wnt/β-catenin pathway-related genes β-catenin and DAT were low, while α-syn expression was high. In the PD cell model, miR-23b-3p was downregulated, the Wnt pathway was inhibited, α-syn was upregulated, neuron autophagy was inhibited, and the revitalization of the Wnt/β-catenin pathway could promote the autophagy of neurons. Coculture of miR-23b-3p-enriched exosomes with MN9D cells confirmed that miR-23b-3p-enriched exosomes could promote autophagy in MN9D cells in a PD cell model. Moreover, animal experiments confirmed the results of the cell experiments. Therefore, miR-23b-3p-enriched mesenchymal stem cell exosomes promote neuronal autophagy by regulating the Wnt signaling pathway, thus alleviating PD progression and providing an important basis for the clinical treatment of PD.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the gradual death of dopaminergic neurons. Brain-derived neurotrophic factor (BDNF) and its receptors are widely distributed throughout the central nervous system, which can promote the survival and growth of neurons and protect neurons. This study revealed that BDNF promotes STAT3 phosphorylation and regulates autophagy in neurons. The PD mouse model was established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Moreover, SH-SY5Y cells were treated with 1-methyl-4-phenyl-pyridinium (MPP+) to establish a PD cell model. The level of BDNF was low in PD model mice and SH-SY5Y cells treated with MPP+. BDNF enhanced the levels of p-TrkB, P-STAT3, PINK1, and DJ-1. BDNF promoted autophagy, inhibited the level of p-α-syn (Ser129) and enhanced cell proliferation. The autophagy inhibitor 3-Methyladenine (3-methyladenine, 3-MA) reversed the protective effects of BDNF on neurons. BiFC assay results showed that there was a direct physical interaction between BDNF and STAT3, and coimmunoprecipitation experiments indicated an interaction between STAT3 and PI3K. The PI3K agonist Recilisib activated the PI3K/AKT/mTOR pathway, promoted autophagy, and alleviated neuronal cell damage. BDNF alleviates PD pathology by promoting STAT3 phosphorylation and regulating neuronal autophagy in SH-SY5Y cells and cultured primary neurons. Finally, BDNF has neuroprotective effects on PD model mice.

Background. Parkinson’s disease (PD) is a very common neurodegenerative disease that adversely affects the physical and mental health of many patients, but there is currently no effective treatment. Objective. To this end, this study focused on investigating the potential mechanisms leading to dopaminergic neuronal apoptosis in PD. Methods. Rotenone induces damage in dopaminergic neuronal MN9D cells. Apoptosis was detected by flow cytometry, and the expression of apoptosis-related proteins was detected by western blot. RT-qPCR was used to detect the expression of MALAT1 and miR-23b-3p. The expression of α-synuclein was detected by ELISA. A dual luciferase gene reporter assay was used to determine the targeted regulatory relationship between MALAT1 and miR-23b-3p and miR-23b-3p and α-synuclein. MN9D supernatant was cocultured with BV-2 cells, or BV-2 cells were treated with exogenous α-synuclein and then treated with an autophagy inhibitor (3-MA) and autophagy activator (RAPA). The expression of α-synuclein in BV-2 cells was detected by immunofluorescence. The expression of MIP-1α, a marker of microglial activation, was detected by ELISA. The nuclear translocation of NF-κB p65 was detected by immunofluorescence. The expression of proinflammatory cytokines was detected by ELISA. Western blotting was used to detect the expression of autophagy-related proteins. Apoptosis of MN9D cells was detected after coculture of BV-2 supernatant with MN9D. Results. The expression of MALAT1 and α-synuclein was upregulated, while the expression of miR-23b-3p was downregulated in damaged MN9D cells, resulting in cell apoptosis. MALAT1 can negatively regulate the expression of miR-23b-3p, while miR-23b-3p negatively regulates the expression of α-synuclein. α-synuclein can enter BV-2 cells through cell phagocytosis. Coculture of BV-2 cells with α-synuclein or with MN9D supernatant overexpressing MALAT1 resulted in a decrease in the autophagy level of BV-2 cells and an inflammatory reaction. However, miR-23b-3p mimics and knockdown of α-synuclein reversed the effect of MALAT1 on autophagy and the inflammatory response of BV-2 cells. In addition, after coculture of BV-2 cells with α-synuclein, the level of autophagy further decreased when 3-MA was added, while the opposite result occurred when RAPA was added. After coculture of α-synuclein-treated BV-2 cell supernatant with MN9D cells, autophagy-impaired BV-2 promoted the apoptosis of MN9D cells, and 3-MA aggravated the autophagy disorder of BV-2 and further promoted the apoptosis of MN9D cells, while RAPA reversed the autophagy disorder of BV-2 and alleviated the apoptosis of MN9D cells. Conclusion. MALAT1 can promote α-synuclein expression by regulating miR-23b-3p, thereby inducing microglial autophagy disorder and an inflammatory response leading to apoptosis of dopaminergic neurons. This newly discovered molecular mechanism may provide a potential target for the treatment of PD.

帕金森病(Parkinson's disease,PD)是一种以运动和非运动为特征的慢性、进行性神经退行性疾病,主要是由于大脑黑质中多巴胺能神经元(Dopaminergic neuron、DAN)的逐渐丧失,表现出静止性震颤、强直、姿势不稳定和运动迟缓等主要特征.长链非编码RNA(Long non-coding RNA,LncRNA)是长度超过200个核苷酸,无蛋白质编码能力的RNA,但可参与调控细胞的各种生物过程.LncRNA通过参与α-突触核蛋白(α-Synuclein,α-Syn)、线粒体功能障碍、氧化应激、钙稳定、轴突传输和神经炎症等不同的生理过程在RNA的转录水平、表观遗传调控或转录后水平参与PD的病理进程,对PD的发病机制和疾病进展的有重要的影响.在这里,我们回顾了与PD相关的常见LncRNA(Malat1、SNHG1、LncRNA-p21、NEAT1、AS UCHL1、HOTAIR、HAGLROS)相关研究,为基于lncRNA的PD的诊断、治疗及预后提供新的思路.

OBJECTIVE:This study sought to evaluate the feasibility of multifunctional gastrodin (GAS)-containing nano-drug carrier system against cerebral ischemia-reperfusion injury (CIRI).METHODS:The drug-loaded nanocomposite (Au-G5.NHAc-PS/GAS) with certain encapsulation efficiency (EE) was prepared by physical adsorption method using different proportions of GAS and drug-carrying system (Au-G5.NHAc-PS). High-performance liquid chromatography was used to determine the drug loading and EE. Cultured rat astrocytes and hypothalamic neurons were assigned into four groups: PBS, Au-G5.NHAc-PS, Au-G5.NHAc-PS/GAS, and GAS. CCK-8 assay, flow cytometry, and quantitative real-time PCR were performed to examine the cell viability, apoptosis, and the expression of tumor necrosis factor-α (TNF-α), IL-1β, and IL-6 in the astrocytes and hypothalamic neurons, respectively. Cellular uptake of GAS and Au-G5.NHAc-PS/GAS was analyzed by using Hoechst 33342 staining. The animal model with focal cerebral ischemia was generated by middle cerebral artery occlusion (MCAO) in healthy male Sprague Dawley (SD) rats, and pathological changes of brain tissue and major organs in the rats were identified by hematoxylin and eosin (HE) staining. Apoptosis in rat astrocytes and hypothalamic neurons was detected by TUNEL staining and flow cytometry.RESULTS:Au-G5.NHAc-PS had a spherical shape with a uniform size of 157.3 nm. Among the nanoparticles, Au-G5.NHAc-PS/GAS with an EE of 70.3% displayed the best release delay effect. Moreover, we observed that in vitro cytotoxicity and cellular uptake of Au-G5.NHAc-PS/GAS were higher than those of GAS, whereas the expression of TNF-α, IL-1β, and IL-6 was significantly downregulated in Au-G5.NHAc-PS/GAS group as compared to G5.NHAc-PS group. Notably, HE staining revealed that although Au-G5.NHAc-PS/GAS had no toxic and side effects on the main organs of rats, it alleviated the damage of brain tissue in the MCAO rats. Besides, Au-G5.NHAc/GAS markedly reduced MCAO-induced apoptosis.CONCLUSION:Au-G5.NHAc-PS showed favorable surface morphology, sustained drug release ability, no measurable toxicity, and good biocompatibility, indicating that GAS exerts anti-inflammatory and antiapoptotic effects on CIRI.

Background: To investigate the safety and efficacy of endovascular embolization of very tiny (≤2 mm) intracranial aneurysms with single coil and summarize experience. Methods: A retrospective analysis was performed for 15 consecutive patients with very tiny aneurysms treated by coil embolization alone or stent-assisted coil embolization between January 2017 and January 2020. 15 patients with six unruptured aneurysms and nine ruptured aneurysms were included in this study. There were eight males and seven females with a mean age of 50.0 ± 5.2 years (range 41 to 57 years old). Intraoperative complications, imaging outcomes, clinical outcomes and follow-up data were analyzed. Results: All aneurysms were embolized with a single coil. Lvis stents were used in all coil assisted embolizations. The embolization success rate was 100%. The average volume embolization ratio (VER) of aneurysm embolization was 53.7 ± 25.5%. An intraoperative aneurysm re-rupture complication occurred in one patient (6.7%). 11 patients (73.3%) had immediate complete occlusion after embolization. After a mean follow-up period of 6.7 ± 1.4 months, 13 patients (86.7%) had complete occlusion. No patients had aneurysm re-rupture, an ischemic event or recurrence during follow-up. All patients achieved favorable clinical outcomes with a modified rankin scale (MRS) of 0-2. Conclusions: This study demonstrates that endovascular embolization of very tiny intracranial aneurysms with a single coil is safe and effective. However, the follow-up period was not long enough and studies with larger numbers of patients are required. The summary of experience reported here is expected to provide significant patient benefits.

BACKGROUND: Surgical resection is a key method for glioma treatment. This inherently invasive procedure alters the tumor microenvironment of glioma cells that cannot be removed by surgery. However, few studies have focused on the impact of this microenvironment change on the growth of glioma cells. METHODS: The authors preconstructed a surgical brain injury model, and then C6 glioma cells were transplanted. HE staining was used to observe the general morphology of tumor cells, and immunohistochemistry of MMP-2, MMP-9, GFAP, and CD31 was used to evaluate the invasiveness of glioma cells and activation of astrocytes and calculate microvessel density. In vitro, primary rat astrocytes were exposed to different temperature gradients. The supernatant was made into conditioned medium for culturing C6 glioma cells. The scratch test and transwell test were used to evaluate the migration and invasion of tumor cells. RESULTS: GFAP expression was stronger in surgical brain injury rats, C6 cells implanted in these rats showed stronger expression of MMP-2 and MMP-9, and CD31 was expressed in more microvessels. Astrocytes exposed to high temperatures of 40 degrees C and 43 degrees C expressed stronger GFAP, and C6 cells cultured in their supernatants had stronger scratch healing ability and the ability to cross transwell chambers. CONCLUSIONS: The microenvironment changes caused by surgical brain injury will enhance the migration and invasion of glioma cells and increase the microvessel density in the tumor. This effect may be related to the activation of astrocytes caused by the thermal injury of bipolar coagulation during surgery.

脊髓损伤(SCI)在临床工作中十分常见,近年来其发病率呈逐年上升趋势.由于神经元损伤后的不可再生性,即使通过各种手段对SCI患者进行积极治疗,效果仍十分有限,这对其身体、心理及情感产生伤害,同时对家庭和社会造成重大经济负担.随着对各种信号通路的深入研究,发现其在神经损伤与修复过程中都起着重要调控作用,尤其是在神经干细胞增殖、分化和代谢中起着关键作用,这为SCI的修复提供了新的方向.其中Wnt、Notch、TGF-β/Smads、mTOR信号通路在SCI修复过程中的分子机制是目前研究热点,本文对SCI相关信号通路在SCI修复过程中的研究成果和进展作一综述.

Objective:To explore the clinical effect of microsurgical treatment of hemangioblastoma (HB) in the central nervous system.Methods:The clinical data of 41 HB patients who underwent microsurgery from January 2016 to January 2020 at Department of Neurosurgery, the First Affiliated Hospital of Kunming Medical University were retrospectively analyzed. Three of them were complicated with Von Hippel-Lindau (VHL) syndrome. Before tumor resection, 2 cases underwent ventricular-abdominal shunting; 1 case underwent third ventriculostomy connecting the third ventricle with the interpeduncular cistern; 3 cases underwent partial embolization of the blood supply artery. Intraoperative neuroelectrophysiological monitoring was performed in all patients. Intraoperative real-time ultrasound with preoperative MRI fusion technology was used in 2 cases, and auxiliary neuroendoscopy was employed in 2 cases. The Karnofsky neurological function score (KPS) was used to evaluate the clinical efficacy at 3 months post operation, and the tumor recurrence was followed up by imaging.Results:Among 41 patients, total resection of tumor was achieved in 40 cases (97.6%) and partial resection in 1 case (2.4%). One patient (2.4%) died of intracranial infection after surgery, and two patients (4.9%) developed severe lung infection. At 3-month follow-up, 30 out of 40 patients (75.0%) had symptomatic improvement, and 10 patients (25.0%) had no significant changes in symptoms compared with preoperative conditions. The KPS score was 79.8±15.3 points, which had significant difference from preoperative score (70.2 ±14.9 points) ( P=0.011). MRI examination showed that 4 cases (10.0%) had recurrence in the original location or new lesions in distant regions, of which 3 cases were patients with VHL and underwent radiation treatment resulting in tumor shrinkage on follow-up MRI. Conclusions:With the combination of multiple techniques, the total resection rate of HB in the central nervous system seems high with low incidence of complications. HB patients with VHL syndrome may have a higher chance of tumor recurrence rate after surgery.

BACKGROUND:Spinal cord injury (SCI) is a life-changing event with an extremely poor prognosis. In our preliminary studies, electroacupuncture (EA) was found to promote the repair of SCI, which was closely related to the Notch signaling pathway. Therefore, in the present study, we hypothesized that EA protects against SCI by inhibiting the Notch signaling pathway and sought to investigate the underlying molecular mechanisms.METHODS:Rat and cell models of SCI were established. The expression of long non-coding RNA H19 was measured by real-time quantitative polymerase chain reaction. The expression levels of EZH2, Notch1, Notch3, Notch4, Hes1, and PS1 protein were measured by western blot. Cell apoptosis and viability were analyzed using flow cytometry and Cell Counting Kit-8 assays, respectively. The expressions of glial fibrillary acidic protein (GFAP) and nestin were detected by immunofluorescence staining.RESULTS:The expressions of H19, EZH2, and GFAP were significantly increased after SCI but were inhibited by EA; in contrast, nestin expression was significantly decreased by SCI but was restored by EA. Moreover, oxygen-glucose deprivation (OGD) treatment elevated the expression of H19, EZH2, and Notch-related factors as well as apoptosis in PC-12 cells, while suppressing cell viability. Suppressing H19 alleviated the effects of OGD on cell viability and apoptosis, and inhibited the expression of EZH2 and Notch-related factors expression; these effects were reversed by EZH2 overexpression. Finally, EA promoted the recovery of SCI rats and neural stem cell (NSC) proliferation by inhibiting the Notch signaling pathway, which was reversed by H19 overexpression.CONCLUSIONS:Our results demonstrated that EA promotes the recovery of SCI rats and increases the proliferation and differentiation of NSCs by suppressing the Notch signaling pathway via modulating the H19/EZH2 axis.

Objective: Tiny intracranial aneurysms pose a great therapeutic challenge for endovascular embolization due to the difficulties in coil packing and risk of intraoperative aneurysm re-rupture. These aneurysms are defined as the maximum diameter of less than or equal to 3 mm. This study was designed to explore the clinical efficacy and prognosis of endovascular embolization in the treatment of ruptured tiny intracranial aneurysms. Method: A total of 46 patients with 46 ruptured tiny intracranial aneurysms admitted to our hospital were retrospectively analyzed and evaluated for clinical efficacy and follow-up results by the Modified Rankin Scale (MRS). Clinical efficacy was assessed by the embolization degree of aneurysms and perioperative complications. According to patients' MRS scores at 12 months after discharge, univariate analysis was performed for gender, age, hypertension, diabetes, smoking, Hunt-Hess grade (HHG), Modified Fisher Scale (MFS), time from admission to embolization, aneurysm location, embolization method, embolization degree and perioperative complications, and factors with statistically significant differences were included in multivariate logistic regression analysis. Results: There were 37 patients (80.4%) with complete embolization. Of the remaining 9 patients, 4 patients (8.7%) were found with sub-complete embolization and 5 patients (10.9%) with incomplete embolization. In the process of embolization, there were 4 cases (8.7%) of cerebral vasospasm, 3 cases (6.5%) of acute thrombosis and 3 cases of intraoperative aneurysm re-rupture. The postoperative complications included cerebral infarction in 2 cases (4.3%), serious hydrocephalus in 1 case (2.2%) and severe pulmonary infection in 1 case (2.2%). After treatment, the proportion of MRS score 0 and 1 was significantly higher than that at admission (P<0.05). During the follow-up of all patients for 12 months, 35 patients (76.1%) had good prognosis and 11 patients (23.9%) had poor prognosis. Univariate analysis showed that HHG, MFS and perioperative complications were the factors affecting the prognosis of patients (P<0.05), and were the independent risk factors affecting the prognosis of patients with ruptured tiny intracranial aneurysms (P<0.05). Conclusion: Endovascular embolization has been proven effective in the treatment of patients with ruptured tiny intracranial aneurysms. HHG, MFS and perioperative complications are significantly correlated to poor prognosis of patients, which is worthy of attention.

BACKGROUND:Ischemic stroke leads to a long-term disability in humans and no efficient clinical therapy exists to date. The middle cerebral artery occlusion (MCAO) model in non-human primates has shown to be of value for translational stroke research. New method In the current study, a photothrombotic (PT) stroke model was established in rhesus monkeys with either a proximal or distal segment of middle cerebral artery (MCA) thrombosis. This study is the first that compares the two approaches of PT stroke in monkeys using behavioral and physiological measurements and MRI scans.RESULTS:The experiment found that infarct occurred in the MCA target regions, with all monkeys having impaired behavior reflected by deficits in neurologic function, and motor and cognition in object retrieval detour (ORD) task. The monkeys with distal MCA thrombosis developed with sequential photo-irritations of the Sylvian fissure zone, adjacent central anterior gyrus and central posterior gyrus, had similar impairments with respect to behavior and showed a tendency of a small edema volume with proximal MCA thrombosis at days 4 and 7 post PT stroke.COMPARISON WITH EXISTING METHODS:The distal MCA thrombosis developed with sequential photo-irritations might provide a consistent and well-tolerated focal ischemia in rhesus monkeys, compared with other PT stroke models which usually were singly conducted on the animal's motor cortex and had a temporal effect.CONCLUSIONS:The sequentially photo-irritated PT stroke model is a promising ischemic stroke model in rhesus monkey for studying human stroke pathology and physiology and for new therapies development.