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The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression, and participates in cytokine secretion in many diseases. However, the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied. A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool. Some rats were first treated with JAK2/STAT3 small interfering RNA (Si-JAK2/Si-STAT3) or overexpression plasmids of JAK2/STAT3. In the brains of subarachnoid hemorrhage model rats, the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated, reaching a peak at 48 hours after injury. Simultaneously, the interactions between JAK2 and SOCS1 were reduced. In contrast, the interactions between JAK2 and STAT3 were markedly enhanced. Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis, destruction of the blood-brain barrier, brain edema, and cognitive functional impairment after subarachnoid hemorrhage. This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein, decreased total levels of JAK2 and STAT3 protein, and increased SOCS1 protein expression. However, overexpression of JAK2 and STAT3 exerted opposite effects, aggravating subarachnoid hemorrhage-induced early brain injury. Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors (inducible nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α) and increased the release of anti-inflammatory factors (arginase-1, interleukin-10, and interleukin-4). Furthermore, primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro, and the JAK2 inhibitor AG490 was used as an intervention. The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression. Together, our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in vivo by inducing inflammatory responses. This study was approved by the Animal Ethics Committee of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China (approval No. LLSC-20180202) on March 1, 2018.

Parkinson's disease (PD) is a common neurodegenerative disease with strong heterogeneity of clinical symptoms and progressive aggravation. The core pathological feature is the apoptosis of dopaminergic neurons in substantia nigra and striatum, but this pathological feature can only explain part of the symptom. With the development of electrophysiological recording, fMRI, optogenetics and other technologies, it has been found that neural circuit dysfunction after dopaminergic neuron apoptosis is an important mechanism for the occurrence and development of PD, as well as many therapeutic measures such as deep brain stimulation (DBS) intervention target. This article reviews the research progress of PD neural circuit mechanism in recent years, including common symptoms of PD, neural circuit models, and abnormal electrical activity patterns, to provide ideas for clinical research. DOI：10.3969/j.issn.1672⁃6731.2020.12.002

Objective To investigate the feasibility and efficacy of deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD) after pallidum or thalamus lesion, and to analyze its therapeutic strategy. Methods From December 2013 to December 2019, nine patients with PD whose symptoms recurred after nuclear lesion and underwent DBS were selected. MRI combined with microelectrode recording (MER) technology was used to locate the target, and patients were treated with DBS. The adverse events during and after awake anesthesia and postoperative follow⁃up were observed to evaluate the safety of operation, Unified Parkinson's Disease Rating Scale (UPDRS) and Activities of Daily Living Scale (ADL) were used to evaluate the improvement of postoperative symptoms and the efficacy of DBS. Results In this group of 9 patients, 2 patients were treated with unilateral subthalamic nucleus (STN) ⁃ DBS, the remaining 7 cases were treated with bilateral STN ⁃ DBS; the cell discharge frequency recorded on the ipsilateral and contralateral sides of the lesion was 400-500 Hz, without significant difference. There were no intraoperative and postoperative complications, and the symptoms of all patients were improved in varying degrees. After 3 months of stimulation, the UPDRS score of PD patients decreased from (115.56 ± 26.17) score to (32.56 ± 9.08) score, the difference was statistically significant (t = 10.853, P = 0.000); and the ADL score increased from (38.56 ± 6.09) score to (73.68 ± 19.07) score, the difference was statistically significant (t = 10.850, P = 0.000). There was no postoperative complication. Conclusions For PD patients who had undergone unilateral pallidotomy or thalamus lesion, if limb stiffness/tremor symptoms exist, as long as the STN nuclei have complete anatomical structure, selective STN⁃DBS assisted by MER is safe and feasible, and bilateral STN⁃DBS would be better. DOI：10.3969/j.issn.1672⁃6731.2020.12.004

Deep brain stimulation (DBS) was first used in the treatment of essential tremor in 1987, and later used in the treatment of advanced Parkinson's disease (PD), drug⁃refractory dystonia, other types of tremor and Tourette's syndrome, which can reduce the clinical symptoms and improve quality of life of patients for a long time, as a major progress in surgical treatment of movement disorders in past 30 years. However, there are also limitations that can not effectively improve the axial system symptoms of PD, secondary dystonia, or related side effects such as cognitive impairment and balance disorder. In recent years, the exploration of new targets and innovation of DBS equipment have further promoted the treatment of DBS for movement disorders. This article reviews relevant research to provide clinical guidance. DOI：10.3969/j.issn.1672⁃6731.2020.12.001

Objective To explore the characteristics of resting⁃state amplitude of low⁃frequency fluctuation (ALFF) and functional connectivity (FC) in patients with Parkinson's disease (PD) and working memory impairment, and to explore its correlation with cognitive function in order to reveal the abnormal neuronal activity and possibility of brain regions related to working memory impairment neuroimaging mechanism. Methods Thirty⁃nine patients with primary PD from January 2019 to September 2020 were enrolled, using Mini ⁃ Mental State Examination (MMSE), Digital Span Test [DST, including Digit Span Forward Test (DSFT) and Digit Span Backward Test (DSBT)], Clock Drawing Test (CDT) and Animal Verbal Fluency Test (VFT) to evaluate the cognitive function, resting⁃state fMRI (rs⁃fMRI) examination, calculation of ALFF value and FC value between different brain regions and the whole brain. The corrdation between ALFF value and the cognitive function was analysed by Spearman rank correlation. Results According to the DSFT score, 39 patients were divided into PD with working memory impairment group (PD⁃WI group,n = 17) and PD without working memory impairment group (PD⁃normal group, n = 22). MMSE total score (Z = ⁃ 2.149, P = 0.032) and memory (Z = ⁃ 2.465, P = 0.014), attention and calculation (Z = ⁃ 2.239, P = 0.025), language function (Z = ⁃ 2.575, P = 0.010) scores, and DST (Z = ⁃ 5.357, P = 0.000) scores, DSBT (Z = ⁃ 3.967, P = 0.000) and CDT (Z = ⁃ 3.410, P = 0.001) scores in PD⁃WI group were lower than those in PD⁃ normal group. The increased ALFF value was mainly located in the right posterior cingulate gyrus, right thalamus and right precuneus (GRF correction; voxel P < 0.05, cluster P < 0.05). The right posterior cingulate gyrus was the region of interest (ROI). The brain regions with increased FC value were mainly located in the left orbital middle frontal gyrus and the right lingual gyrus (GRF correction; voxel P < 0.05, cluster P < 0.05). Spearman rank correlation analysis showed that the ALFF value at the right cingulate was negatively correlated with the DSFT score (rs = ⁃ 0.530, P = 0.001). Conclusions PD with working memory impairment patients have different degrees of cognitive dysfunction. The spontaneous neuronal activity in the right posterior cingulate gyrus of the core brain region of the brain default network is enhanced and its correlation with the left orbital middle frontal gyrus and the right lingual gyrus, which is a compensation for early working memory impairment. DOI：10.3969/j.issn.1672⁃6731.2020.12.003

Gliosarcoma (GSM), a histologic variant of glioblastoma (GBM), carries a poor prognosis with less than one year of median survival. Though GSM is similar with GBM in most clinical and pathological symptoms, GBM has unique molecular and histological features. However, as the rarity of GSM samples, the genetic information of this tumor is still lacking. Here, we take a comprehensive analysis of DNA copy number variations (CNV) in GBM and GSM. Whole genome sequencing was performed on 21 cases of GBM and 15 cases of GSM. CNVKIT is used for CNV calling. Our data showed that chromosomes 7, 8, 9, and 10 were the regions where CNV frequently happened in both GBM and GSM. There was a distinct CNV signal in chromosome 2 especially in GSM. The pathway enrichment of genes with CNV was suggested that the GBM and GSM shared the similar mechanism of tumor development. However, the CNV of some screened genes displayed a disparate form between GBM and GSM, such as AMP, BEND2, HDAC6, FOXP3, ZBTB33, TFE3, and VEGFD. It meant that GSM was a distinct subgroup possessing typical biomarkers. The pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.

Objective To explore the expression of long non⁃coding RNA (lncRNA) SNORD3A in glioma tissues and cell lines and its effect on proliferation and invasion of glioma cells. Methods We analyzed the differentially expressed lncRNAs in the National Center for Biotechnology Information (NCBI) GEO (GSE58276) by bioinformatics. A total of 30 glioma tissue specimen were collected from June 2017 to August 2019, lncRNA SNORD3A expression was detected by real⁃time fluorescence quantitative polymerase chain reaction (PCR). The si⁃SNORD3A was transfected into T98G and U251 cells. CCK⁃8 was used to analyze the proliferative capacity of cells. Transwell assay was used to detect cell invasion changes. The expression of c⁃Myc protein was detected by Western blotting. Results Compared with the control group, the expression level of lncRNA SNORD3A in glioma tissue was increased (P = 0.000). Compared with HEB cells, the expression levels of T98G, U87, U251 and U373 lncRNA SNORD3A in glioma cell lines were elevated (P < 0.05, for all). The expression levels of lncRNA SNORD3A in T98G cells (P = 0.001, 0.007) and U251 cells (P = 0.002, 0.009) in si⁃SNORD3A⁃1 group and si⁃SNORD3A⁃2 group were lower than those in control group. At 24, 48 and 72 h after transfection, the proliferation capacity of T98G cells (P = 0.000, for all) and U251 cells (P = 0.000, for all) in si⁃SNORD3A⁃1 and si⁃SNORD3A⁃2 groups were lower than those in control group. At 48 h after transfection, the number of T98G and U251 cells passing through the chamber in si⁃SNORD3A⁃1 and si⁃SNORD3A⁃2 groups were less than those in control group (P = 0.000, for all), and the levels of c⁃Myc mRNA and protein expression were lower than control group (P < 0.01, for all). Conclusions lncRNA SNORD3A promotes proliferation and invasion of T98G and U251 cells by partly targeting c⁃Myc. DOI：10.3969/j.issn.1672⁃6731.2019.12.007

The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage. Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham (injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1 (rhwnt1), small interfering Wnt1 (siwnt1) RNA, and monoclonal antibody of Frizzled1 (anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, β-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and β-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury (within 72 hours), including cortical cell apoptosis, brain edema, and neurobehavioral deficits, accompanied by increasing protein levels of β-catenin, CD36, and peroxisome proliferator-activated receptor-γ and decreasing protein levels of nuclear factor-κB. Of note, rhwnt1 promoted M2-type microglia conversion and inhibited release of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α). In contrast, siwnt1 RNA and anti-Frizzled1 treatment both resulted in an opposite effect. In conclusion, the Wnt/Frizzled1 signaling pathway may participate in subarachnoid hemorrhage-induced early brain injury via inhibiting the inflammatory response, including regulating microglia type conversion and decreasing inflammatory cytokine release. The study was approved by the Animal Ethics Committee of Anhui Medical University and First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (approval No. LLSC-20180202) in May 2017.

Conserved dopamine neurotrophic factor protects and rescues dopaminergic neurodegeneration induced by 6-hydroxydopamine in vivo, but its potential value in treating Parkinson's disease remains controversial. Here, we used the proteasome inhibitors lactacystin and MG132 to induce neurodegeneration of PC12 cells. Afterwards, conserved dopamine neurotrophic factor was administrated as a therapeutic factor, both pretreatment and posttreatment. Our results showed that (1) conserved dopamine neurotrophic factor enhanced lactacystin/MG132-induced cell viability and morphology, and attenuated alpha-synuclein accumulation in differentiated PC12 cells. (2) Enzyme linked immunosorbent assay showed up-regulated 26S proteasomal activity in MG132-induced PC12 cells after pre- and posttreatment with conserved dopamine neurotrophic factor. Similarly, 26S proteasome activity was upregulated in lactacystin-induced PC12 cells pretreated with conserved dopamine neurotrophic factor. (3) With regard proteolytic enzymes (specifically, glutamyl peptide hydrolase, chymotrypsin, and trypsin), glutamyl peptide hydrolase activity was up-regulated in lactacystin/MG132-administered PC12 cells after pre- and posttreatment with conserved dopamine neurotrophic factor. However, upregulation of chymotrypsin activity was only observed in MG132-administered PC12 cells pretreated with conserved dopamine neurotrophic factor. There was no change in trypsin expression. We conclude that conserved dopamine neurotrophic factor develops its neurotrophic effects by modulating proteasomal activities, and thereby protects and rescues PC12 cells against neurodegeneration.

Objective To explore the methods and curative effect of stereotactic surgery for treating writer's cramp (WC). Methods and Results Two patients with writer's cramp (tremor type) underwent MRI guided stereotactic ventrointermediate (Vim) thalamotomy on the left side. The symptoms of one patient disappeared immediately after operation, and the patient could write legibly. The tremor of right upper extremity in another patient was improved significantly. Two patients did not present obvious complications, and the previous symptoms were not found to recur during follow-up period respectively. Conclusions Stereotactic surgery for treatment of writer's cramp has definite therapeutic effect. MRI guided stereotactic technique can effectively avoid the complications of Vim thalamotomy. However, the indications of two methods in surgical treatment [thalamotomy and deep brain stimulation (DBS)] and the respective merits still need further study. DOI: 10.3969/j.issn.1672-6731.2015.10.009

Background Traditional surgical treatments for this rare disease include open surgical procedures and ventriculoperitoneal shunting. In 1995, endoscopic fenestration was first applied to treatment of cysts of the septum pellucidum (CSP). However, cyst fenestration generally takes a bilateral approach by making two burr holes leading to two fenestrations in the lateral walls of the cyst. Some disadvantages are related to bilateral fenestration. So far, there is no consensus on the surgical indications, the endoscopic approaches, and techniques for CSPs. Based on our experience with 14 cases of symptomatic CSP treated with neuronavigation-assisted endoscopic unilateral cyst fenestration via a single burr hole, we discuss the operative indications and the utility of endoscope-assisted techniques in combination with neuronavigation. Methods 14 patients underwent endoscopic CSP fenestration via a right frontal approach using a rigid endoscope and neuronavigation. Neuronavigation helped locating optimal skin incision, puncture point, optimal operation trajectory, and real-time operation monitoring. Postoperatively, a follow-up study on the 14 patients was performed. Results The follow-up period ranged from 6 months to 2 years. Postoperatively, the mass effect of the cysts and the self-reported symptoms disappeared immediately. In 7 patients with papilledema, the optic fundus examinations showed that papilledema improved. The computerized tomography (CT) or magnetic resonance imaging (MRI) scans showed significant decrease in the cyst size and no recurrence during the followup. In 2 patients with accompanying hydrocephalus, the hydrocephalus disappeared. Conclusion The results after uni- and bilateral CSP fenestration show no significant difference. Avoiding damage of contralateral tissue, the surgical trauma in unilateral fenestration is less than in bilateral fenestration. Furthermore, the unilateral approach shortens the operation time. We believe that unilateral cyst fenestration is a better therapeutic option in symptomatic CSP. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of all-trans retinoic acid(ATRA) on the proliferation and differentiation of brain tumor stem cells(BTSCs) in vitro. Methods: Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP) in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS) were observed. Results: BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P < 0.01). In serum-containing medium, the expression percentages of CD133 and GFAP in the differentiated BTSCs were (2.29% ± 0.27%) and (75.60% ± 4.03%) respectively in the ATRA group, and (7.05% ± 0.49%) and (12.51% ± 0.77%) respectively in the control group. The differentiation rate of BTSCs in the ATRA group was significantly higher than that in the control group (P < 0.05), but there was still CD133 expressed in the ATRA group. The differentiated BTSCs could re-form BTSs in serum-free medium. The percentage of BTS formation in the ATRA group was(4.84% ± 0.32%), significantly lower than that in the control group (17.71% ± 0.78%) (P < 0.05), and the time required for BTS formation in the ATRA group was (10.07 ± 1.03)d, significantly longer than that in the control group (4.08 ± 0.35)d (P < 0.05). Conclusion: ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again. [ABSTRACT FROM AUTHOR]