Temozolomide (TMZ) resistance is a critical factor that affects the therapeutic efficacy in glioblastoma (GBM). Glutathione peroxidase 8 (GPX8), a ROS scavenging enzyme, is associated with poor prognosis in GBM. In this study, we comprehensively studied the role and mechanism of GPX8 in GBM resistance to TMZ. We found that GPX8 was upregulated in GBM cells, tissues, and TMZ-resistant GBM cells. In U87 TMZ-resistant cells, GPX8 knockdown significantly suppressed cell proliferation, reversed the epithelial-mesenchymal transition (EMT), and sensitized cells to TMZ. Moreover, GPX8 knockdown induced mitochondrial oxidative stress, leading to apoptosis in TMZ-resistant cells. TEA domain family member 4 (TEAD4) was upregulated in GBM cells and transactivates GPX8. GPX8 interacted with collagen triple helix repeat containing-1 (CTHRC1) and promoted its expression. Overexpression of TEAD4 or CTHRC1 reversed the suppressive effect of GPX8 knockdown on the malignant phenotypes of TMZ-resistant cells and antagonized its promotive effect on mitochondrial ROS generation and apoptosis. Furthermore, overexpression of GPX8 or CTHRC1 promoted EMT, reduced ROS levels, and lowered TMZ sensitivity in resistant cells. Crucially, the p38 MAPK/FOXO3 pathway inhibitor Ade was able to reverse these effects. GPX8 knockdown increased GBM sensitivity to TMZ, inhibited EMT, and elevated ROS levels in both xenograft models and glioma organoids. Overall, our results elucidated that TEAD4-driven GPX8 suppresses mitochondrial oxidative stress in TMZ-resistant cells through activation of the CTHRC1/p38 MAPK/FOXO3 pathway, which promotes TMZ resistance in GBM cells. These findings suggest that GPX8 may serve as a novel therapeutic target for overcoming TMZ resistance in GBM.

Previous studies have suggested that N6-methyladenosine (mA) modification of RNA affects fundamental aspects of RNA metabolism, and mA dysregulation is implicated in various human diseases, including Alzheimer’s disease (AD). This study is designed to explore the role and mechanism of methyltransferase-like 14 (METTL14) in the pathogenesis of AD. SK-N-SH cells were treated with Aβ1–42 to establish an in vitro model of AD. Cerebellin 4 (CBLN4) and METTL14 expression levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were analyzed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry assay. B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), C-caspase-3, total-caspase-3, C/EBP homologous protein (CHOP), and glucose-related protein 78 (GRP78) protein levels were determined using Western blot. Interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) levels were analyzed using ELISA. Reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) products were examined using special assay kits. Interaction between CBLN4 and METTL14 was verified using methylated RNA immunoprecipitation (MeRIP) and dual-luciferase reporter assays. CBLN4 and METTL14 expression was decreased in Aβ1-42-treated SK-N-SH cells. Upregulation of CBLN4 relieved Aβ1-42-induced SK-N-SH cell apoptosis, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress in vitro. At the molecular level, METTL14 could improve the stability and expression of CBLN4 mRNA via m6A methylation. Our findings indicated that m6A methylase METTL14-mediated upregulation of CBLN4 mRNA stability could repress Aβ1-42-triggered SK-N-SH cell injury, providing a promising therapeutic target for AD treatment.

Glioblastoma (GBM) is the most aggressive form of brain cancer, characterized by rapid growth and invasion into surrounding brain tissue. Ubiquitin-specific protease 9X (USP9X) has emerged as a key regulator in various cancers, but its role in GBM pathogenesis remains unclear. Understanding the molecular mechanisms underlying USP9X modulation of GBM progression could unveil potential therapeutic targets for this deadly disease. The mRNA and protein levels were determined in GBM tissues and/or cells using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting assays, respectively. Cell migration was evaluated through wound-healing assay, while cell proliferation was measured using colony formation and CCK-8 assays. Flow cytometry analysis was performed to quantify the CD206-positive macrophages to assess M2 polarization. Co-immunoprecipitation (Co-IP) assays were conducted to elucidate the association between USP9X and transformation/transcription domain-associated protein (TRRAP). Cycloheximide (CHX) treatment was used to determine the impact of USP9X on TRRAP protein stabilization. Furthermore, the effect of USP9X depletion on GBM cell malignancy was validated using a xenograft mouse model. We found that USP9X expression was elevated in GBM tissues and cells. Depletion of USP9X suppressed GBM cell migration, proliferation, and M2 macrophage polarization. Mechanistically, USP9X stabilized TRRAP through the deubiquitination pathway in GBM cells, and TRRAP mitigated the effects of USP9X silencing on GBM cell malignant phenotypes and M2 macrophage polarization. Moreover, silencing of USP9X inhibited tumor formation in vivo. Together, USP9X deubiquitinated TRRAP, thereby promoting glioblastoma cell proliferation, migration, and M2 macrophage polarization. These results highlight the potential of targeting the USP9X-TRRAP axis as a therapeutic strategy for GBM.

The function of glioma stem cells (GSCs) is closely related to the progression of glioblastoma multiforme (GBM). Centromere protein A (CENPA) has been confirmed to be related to the poor prognosis of GBM patients. However, whether CENPA regulates GSCs function to mediate GBM progression is still unclear. GSCs were isolated from GBM cells. The expression of CENPA and guanylate-binding protein 2 (GBP2) was examined by quantitative real-time PCR and western blot. GSCs proliferation and stemness were assessed using EdU assay and sphere formation assay. Cell ferroptosis was evaluated by detecting related factors. The interaction between CENPA and GBP2 was analyzed by ChIP assay and dual-luciferase reporter assay. Animal experiments were conducted to measure the effect of CENPA knockdown on the tumorigenicity of GSCs in vivo. CENPA was upregulated in GBM tissues and GSCs. CENPA knockdown inhibited GSCs proliferation, stemnness, and promoted ferroptosis. GBP2 was overexpressed in GBM tissues and GSCs, and CENPA enhanced GBP2 transcription by binding to its promoter region. CENPA overexpression accelerated GSCs proliferation and stemnness and suppressed ferroptosis, while GBP2 knockdown reversed these effects. Downregulation of CENPA reduced the tumorigenicity of GSCs by decreasing GBP2 expression in vivo. In conclusion, CENPA enhanced GBP2 transcription to increase its expression, thus accelerating GSCs proliferation and stemnness and repressing ferroptosis. Our findings promote a new idea for GBM treatment.

The predictors of seizure outcomes after resective surgery for focal epilepsy, for an update on the features of good and poor outcomes, are investigated. A retrospective study of patients with focal epilepsy undergoing resective surgery from March 2011 to April 2019 was performed. There were 3 groups according to the seizure outcomes: seizure freedom, seizure improvement, and no improvement. Predictors of seizure outcomes were identified by multivariate logistic regression analysis. Of all 833 patients, 561 (67.3%) patients remained seizure-free at the last follow-up, 203 (24.4%) patients had seizure improvement, and 69 (8.3%) had no improvement. The mean follow-up duration was 5.2 years (range: 2.7 to 9.6). Predictors of better outcomes included epilepsy duration < 5 years, localized discharge, no. of antiepileptic drugs at surgery < 3, and temporal lobe resection. However, predictors of worse outcomes included intracranial hemorrhage in infancy, interictal abnormal discharge, intracranial electrode monitoring, and acute postoperative seizure. Our study suggests that resective surgery for focal epilepsy has satisfactory outcomes. Short epilepsy duration, localized discharge, and temporal lobe resection are positive predictors of seizure freedom. Patients with these predictors are intensively recommended for surgery.

Marizomib is a novel, irreversible, brain-penetrant panproteasome inhibitor with encouraging findings in preclinical models and early-stage clinical trials for patients with newly diagnosed and recurrent glioblastoma. Marizomib (MRZ)-loaded zeolitic imidazolate framework-8 (ZIF-8) and manganese dioxide (MnO2) (termed as MRZ-ZIF-8 @MnO2) nanoparticles, a smart-functional therapeutic system, were prepared for the treatment of glioma cancer. Fourier transforms infrared (FTIR) and transmission electron microscope (TEM) were used to assess the structural and morphology properties of drug-loaded ZIF-8-NPs. The findings demonstrated this drug delivery carrier's narrow and particle size distribution. The anticancer drug MRZ released from the NPs was measured. The cell viability of glioma cancer cells (C6 and U87) treated with NPs was established using the cell counting kit-8. The in vitro proliferation of drug-loaded ZIF-8-NPs was substantially increased than that of free MRZ and drug-loaded ZIF-8-NPs treated cells. In addition, The C6 and U87 cell morphological staining studies, such as dual staining (acridine orange/ethidium bromide, AO/EB) and nuclear staining (4 ',6-diamidino-2-phenylindole, DAPI), ascertain that the drug-loaded ZIF-8-NPs stimulates the apoptosis in glioma cancer cell lines. The results of morphological changes show that a high apoptosis level was found with drug-loaded ZIF-8-NPs. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) validate the apoptotic mode of cancer cell death via the MMP pathway. These findings suggest that the as-fabricated MRZ-ZIF-8 @MnO2-NPs with the synergetic anticancer drug might be applied to treat glioma cancer.

Background Glioma is a major type of brain cancer and responsible for high death rate worldwide due to the delayed diagnosis and chemo-resistance. It is responsible for nearly 16% of all brain cancer incidences with increased prevalence globally. Objective The present research study deals with discovering the in vitro anticancer potential of cirsilineol on the rat glioma C6 cells through the inhibition of PI3K/Akt/mTOR and MAPK signaling pathways. Methodology The in vitro antioxidant potential of cirsilineol was examined by different free radical scavenging analyses. The effects of cirsilineol on the cell viability of C6 and normal Vero cells were investigated by MTT assay. The intracellular ROS production and apoptotic cell death in the cirsilineol-administered C6 cells were scrutinized by fluorescent staining techniques. The contents of TBARS and GSH, SOD and caspase activity were examined using assay kits. The PI3K, mTOR, Akt, ERK1/2, JNK1/2, and p38 expressions in the cirsilineol-supplemented C6 cells were examined by RT-PCR study. Results The cirsilineol treatment appreciably scavenged the DPPH, superoxide, and peroxyl radicals. The cell viability of C6 cells was markedly reduced by the cirsilineol; however, it does not affected the Vero cell viability. The cirsilineol treatment demonstrated the augmented ROS production and apoptosis in the C6 cells. The TBARS level and caspase activity were improved, and GSH level and SOD activity were depleted by the cirsilineol. Cirsilineol effectively inhibited PI3K, mTOR, Akt, ERK1/2, JNK1/2, and p38 expressions in the C6 cells. Conclusion Our findings confirmed that the cirsilineol inhibited cell growth and induced apoptosis in C6 cells by inhibiting the PI3K/Akt/mTOR and MAPK signaling cascades. Hence, it can be a potential candidate to treat the glioma in the future.

Background Recent studies revealed the key role of circular RNA (circRNA) in glioma progression. However, the effect of circ_0000520, also named as circRNA ribonuclease P RNA component H1 (circ_RPPH1), in glioma development was unknown. The study aimed to reveal the role of circ_RPPH1 in glioma cell malignancy. Methods Human astrocytes (NHA) and glioma cell lines (A172 and U251) were employed in this study. Quantitative real-time polymerase chain reaction and western blot were used to check the expression of circ_RPPH1, microRNA-627-5p (miR-627-5p), miR-663a and syndecan 1 (SDC1). Immunohistochemistry assay was conducted to assess the protein expression of nuclear proliferation marker ki67 and matrix metalloprotein 9 (MMP9). Cell viability was assessed by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation and apoptosis were investigated by flow cytometry analysis, 5-Ethynyl-29-deoxyuridine, or cell colony formation assay. Cell migration and invasion were evaluated by transwell assays. The interaction between miRNAs (miR-627-5p and miR-663a) and circ_RPPH1 or SDC1 was identified by a dual-luciferase reporter assay. A mouse model assay was performed to reveal the impact of circ_RPPH1 knockdown on glioma cell malignancy in vivo by analyzing neoplasm volume and weight. Results Circ_RPPH1 and SDC1 expression were significantly increased, whereas miR-627-5p and miR-663a expression were decreased in glioma tissues and cells in comparison with healthy brain tissues or human astrocytes. Circ_RPPH1 depletion led to the decreased cell proliferation, migration and invasion, and the increased cell apoptosis. Additionally, circ_RPPH1 bound to miR-627-5p/miR-663a and mediated glioma cell processes by interacting with them. SDC1 overexpression attenuated miR-627-5p/miR-663a-mediated actions. Moreover, circ_RPPH1 regulated SDC1 expression through interaction with miR-627-5p and/or miR-663a. Furthermore, circ_RPPH1 knockdown inhibited glioma cell malignancy in vivo, accompanied by the decreases of ki67 and MMP9 expression. Conclusion Circ_RPPH1 knockdown inhibited glioma tumorigenesis by downregulating SDC1 by binding to miR-627-5p/miR-663a, showing that circ_RPPH1 might be an effective therapeutic target for glioma.

To evaluate the potential effect of radiofrequency ablation and deep brain stimulation in patients with treatment-refractory Tourette syndrome (TS), this study enrolled thirteen patients with TS who were admitted to our hospital between August 2002 and September 2018. Four patients received a single- or multi-target radiofrequency ablation after local, potentiated, or general anesthesia; eight patients underwent deep brain stimulation (DBS) surgery; and one patient underwent both ablation and DBS surgery. The severity of tics and obsessive compulsive disorder symptoms and the quality of life were evaluated using the Yale Global Tic Severity Scale (YGTSS), Yale–Brown Obsessive Compulsive Scale (YBOCS), and Gilles de la Tourette Syndrome Quality of Life scale (GTS-QOL), respectively, before surgery, one month after surgery, and at the final follow-up after surgery, which was conducted in December 2018. A paired-sample t test and a multiple linear regression analysis were performed to analyze the data. All patients underwent the operation successfully without any severe complications. Overall, the YGTSS total scores at one month post-surgery (44.1 ± 22.3) and at the final visit (35.1 ± 23.7) were significantly decreased compared with those at baseline (75.1 ± 6.2; both p < 0.05). Additionally, the YBOCS scores at one month post-surgery (16.5 ± 10.1) and at the final visit (12.0 ± 9.5) were significantly decreased compared with those at baseline (22.5 ± 13.1; both p < 0.05). Furthermore, the GTS-QOL scores at one month post-surgery (44.0 ± 12.8) and at the final visit (31.0 ± 17.8) were significantly decreased compared with those at baseline (58.4 ± 14.2; both p < 0.05). Results from a multiple linear regression analysis revealed that the improvement in the YGTSS total score was independently associated with the improvement in the GTS-QOL score at one month post-surgery (standardized β = 0.716, p = 0.023) and at the final visit (standardized β = 1.064, p = 0.000). Conversely, changes in YBOCS scores did not correlate with changes in GTS-QOL scores (p > 0.05). Our results demonstrate that tics, psychiatric symptoms, and the quality of life in patients with intractable TS may be relieved by stereotactic ablation surgery and deep brain stimulation. Furthermore, it appears that the improvement in tics contributes more to the post-operative quality of life of patients than does the improvement in obsessive compulsive symptoms.

Objective:To explore the value of visualized endoscopic skull base anatomy training for improving the level of relevant clinical anatomy of young neurosurgeons.Methods:From August 2020 to April 2021, the refresher neurosurgery physicians (aged from 26-32 years old, working in Neurosurgery for 1-4 years) in Neurosurgery Department of First Affiliated Hospital of Xi’an Jiaotong University were trained in skull base endoscopic anatomy. They were divided into experimental and control groups by the random number table. The experimental group received visualized endoscopic skull base anatomy training, and the control group received conventional endoscopic skull base anatomy training. Then all of them underwent the clinical skill test. The test is quantitatively assessed in accordance with the scoring standards set by the department.Results:Twenty-two male neurosurgery fellows were included in the study, with 10 in the experimental group and 12 in the control group. There was no statistical difference between the two groups in age and professional working time (P>0.05). The ability of imaging analysis and surgical planning was higher in the experimental group than that in the control group (P<0.05); the ability of understanding and predicting essential anatomical structures was better in the experimental group than that in the control group (P<0.05); the final overall score of the experimental group was better than the control group (P<0.05); the differences between the two groups were statistically significant (P<0.05).Conclusion:Visualized endoscopic skull base anatomy training is more effective than traditional methods for young neurosurgeons.

Introduction: The objective was to explore the improvements and therapeutic effects of deep brain stimulation on the symptoms and living quality of patients with Parkinson disease. Materials and methods: A total of 82 patients with Parkinson disease who underwent deep brain stimulation in the Neurosurgery Department at The First Affiliated Hospital of Xi'an Jiaotong University from May 2016 to January 2019 were enrolled. The clinical symptoms, disease severity, disability, and quality of life of enrolled patients were evaluated at 1 week before the surgery and 6 months after the surgery. Results: 1. Given the "close" drug status, compared with the preoperative UPDRS (Unified Parkinson's Disease Rating Scale) scores, the sports examinations and activities of daily lives of patients decreased significantly (P<0.01). 2. Compared with the preoperative conditions, the Hoehn- Yahr staging and Schwab and England activities of daily lives were significantly improved during the "open" and "close" periods of the drug status (P<0.01). 3. The PDQ- 39(Quality of life questionnaire for Parkinson-39) total scores of patients after the surgery decreased significantly compared with those before the surgery. Besides, the sports, activities of daily lives, and physical discomfort of patients were greatly improved after the surgery (P< 0.01). Conclusion: Deep brain stimulation precisely.

Temozolomide (TMZ) is the major chemotherapy agent in glioma, and isocitrate dehydrogenase (IDH) is a well-known prognostic marker in glioma. O6-methylguanine-DNA methyltransferase promoter methylation (MGMTmethyl) is a predictive biomarker in overall gliomas rather than in IDH mutant gliomas. To discover effective biomarkers that could predict TMZ efficacy in IDH mutant low-grade gliomas (LGGs), we retrieved data of IDH mutant LGGs from TMZ arm of the EORTC22033-26033 trial as the training-set (n = 83), analyzed correlations between long non-coding RNAs (lncRNAs) and progression-free survival (PFS) using Lasso-Cox regression, and created a risk score (RS) to stratify patients. We identified a three-lncRNA signature in TMZ-treated IDH mutant LGGs. All of the three lncRNAs, as well as the RS derived, were significantly correlated with PFS. Patients were classified into high-risk and low-risk groups according to RS. PFS of the high-risk group was significantly worse than that of the low-risk group (P < 0.001). AUCs of the three-, four-, and five-year survival probability predicted by RS were 0.73, 0.79, and 0.76, respectively. The predictive role of the three-lncRNA signature was further validated in an independent testing-set, the TCGA-LGGs, which resulted in a significantly worse PFS (P < 0.001) in the high-risk group. Three-, four-, and five-year survival probabilities predicted by RS were 0.65, 0.69, and 0.84, respectively. Functions of these three lncRNAs involve cell proliferation and differentiation, predicted by their targeting cancer genes. Conclusively, we created a scoring model based on the expression of three lncRNAs, which can effectively predict the survival of IDH mutant LGGs treated with TMZ.

Background It has been shown that circular RNAs (circRNAs) play a vital role in the progression of glioma. Recently, hsa_circ_0001836 was found to be upregulated in glioma tissues, but the role of hsa_circ_0001836 in glioma remains unclear. Methods EdU staining and flow cytometry assays were used to measure the viability and death of glioma cells. In addition, scanning electron microscopy (SEM) was used to observe the morphology of cells undergoing cell death. Results Hsa_circ_0001836 expression was upregulated in U251MG and SHG-44 cells. In addition, hsa_circ_0001836 knockdown significantly reduced the viability and proliferation of U251MG and SHG-44 cells. Moreover, hsa_circ_0001836 knockdown markedly induced the pyroptosis of U251MG and SHG-44 cells, evidenced by the increased expressions of NLRP1, cleaved caspase 1 and GSDMD-N. Meanwhile, methylation specific PCR (MSP) results indicated that hsa_circ_0001836 knockdown epigenetically increased NLRP1 expression via mediating DNA demethylation of NLRP1 promoter region. Furthermore, downregulation of hsa_circ_0001836 notably induced pyroptosis and inhibited tumor growth in a mouse xenograft model of glioma. Conclusion Collectively, hsa_circ_0001836 knockdown could induce pyroptosis cell death in glioma cells in vitro and in vivo via epigenetically upregulating NLRP1 expression. These findings suggested that hsa_circ_0001836 may serve as a potential therapeutic target for the treatment of glioma.

There has been an increased interest for observational studies or randomized controlled trials exploring the impact of calcium intake on cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic stroke (IS). However, a direct relationship between total calcium intake and CVD has not been well established and remains controversial. Mendelian randomization (MR) studies have been performed to evaluate the causal association between serum calcium levels and CAD risk and found that increased serum calcium levels could increase the risk of CAD. However, MR analysis found no significant association between genetically higher serum calcium levels and IS as well as its subtypes. Hence, three MR studies reported inconsistent effects of serum calcium levels on CAD and IS. Here, we performed an updated MR study to investigate the association of serum calcium levels with the risk of IS using large-scale genome-wide association study (GWAS) datasets. We selected 14 independent genetic variants as the potential instrumental variables from a large-scale serum calcium GWAS dataset and extracted summary statistics corresponding to the 14 serum calcium genetic variants from the MEGASTROKE Consortium IS GWAS dataset. Interestingly, we found a significant association between serum calcium levels and IS risk using the robust inverse-variance weighted (IVW) and penalized robust IVW methods, with β = 0.243 andP= 0.002. Importantly, the MR results from the robust MR-Egger and penalized robust MR-Egger methods further supported the causal association between serum calcium levels and IS risk, with β = 0.256 andP= 0.005. Meanwhile, the estimates from other MR methods are also consistent with the above findings.

As a newly epidemic, 2019 coronavirus disease (COVID-19) with a concentrated outbreak poses a great challenge to medical treatment. The severe and critical patients are complex complicatied with the psychological problems, and the medical staff are overworked and under tremendous psychological pressure. The surgeon participated in emergency medical rescue could provide professional treatment for the patients combined with surgical diseases, as well as specialized training for the non-surgeon crew, to reduce surgical-related mortality. With the advantages of good team consciousness, strong aseptic concept and good psychological quality, the surgeons can quickly adapt to and carry out rescue work under the premise of good self-protection. Surgeons need to develop critical care management concepts and focus on the critical care support equipment. Some suggestions are put forward for the standardized training of resident surgeons to cultivate compound talents. It is hoped that this article can lead to the thinking of how to participate in the emergency medical rescue of infectious diseases among surgeons and provide some enlightenment for future surgical education.

BACKGROUND: Methamphetamine (MA) addiction is one of the most prevalent socioeconomic and health problems worldwide. In recent years, deep brain stimulation (DBS) has increasingly been used for the treatment of addiction. CASE DESCRIPTION: This study reports on 2 MA-dependent patients who received DBS of the nucleus accumbens (NAc). During the approximately 2-year follow-up period, one patient (A) remained abstinent and presented with positive emotional experiences, whereas the other (B) had no significant psychobehavioral changes during stimulation at low-to-moderate voltages and subsequently relapsed. Through coregistration of preoperative magnetic resonance imaging with postoperative computed tomography/magnetic resonance imaging, the DBS electrode of patient A was confirmed to be accurately implanted in the NAc, whereas one side of the electrode of patient B deviated from the target. CONCLUSIONS: These case reports demonstrate that NAc-DBS maybe a possible treatment option for MA addiction.

Drug addiction can be viewed as a chronic psychiatric disorder that is related to dysfunction of neural circuits, including reward deficits, stress surfeits, craving changes, and compromised executive function. The nucleus accumbens (NAc) plays a crucial role in regulating craving and relapse, while the medial prefrontal cortex (mPFC) represents a higher cortex projecting into the NAc that is active in the management of executive function. In this study, we investigated the role of the small conductance calcium-activated potassium channels (SK channels) in NAc and mPFC after morphine withdrawal. Action potential (AP) firing of neurons in the NAc shell was enhanced via the downregulations of the SK channels after morphine withdrawal. Furthermore, the expression of SK2 and SK3 subunits in the NAc was significantly reduced after 3 weeks of morphine withdrawal, but was not altered in the dorsal striatum. In mPFC, the SK channel subunits were differentially expressed. To be specific, the expression of SK3 was upregulated, while the expression of SK2 was unchanged. Furthermore, the AP firing in layer 5 pyramidal neurons of the infralimbic (IL) cortex was decreased via the upregulations of the SK channel-related tail current after 3 weeks of morphine withdrawal. These results suggest that the SK channel plays a specific role in reward circuits following morphine exposure and a period of drug withdrawal, making it a potential target for the prevention of relapse.

Objective To evaluate the long-term efficacy of deep brain stimulation (DBS) for the treatment of primary generalized dystonia (PGD) and to analyze the factors influencing the clinical outcome.Methods We retrospectively analyzed the data of 21 patients with PGD who underwent DBS from December 2004 to April 2013 at Department of Neurosurgery,Tangdu Hospital,Air Force Medical University.DBS targeting the subthalamic nucleus (STN-DBS) was applied in 11 patients,and DBS targeting the globus pallidus internus (GPi-DBS) was performed in 10 patients.The severity of dystonia was assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS).Multiple linear regression analysis was used to explore the factors affecting clinical outcomes.Results The follow-up period ranged from 5 years to 11 years,and the median time was 6.5 years.The average improvement rate of BFMDRS movement scores was 65.7％ ± 13.9％ and the median improvement rate of disability scores was 54.5 ％ [IQR (interquartile range):17.0％] in the 21 patients with PGD at the last follow-up.The mean/median improvement rates of movement score and disability score in STN-DBS group were 64.4％ ± 15.8％ and 57.1％ (IQR:20.2％) respectively,and those in GPi-DBS group were 67.1％ ± 12.2％ and 52.8％ (IQR:18.0％) respectively.There was no significant difference in the average improvement rate of BFMDRS movement score or disability score between STN-DBS and GPi-DBS group (both P ＞ 0.05).Multiple linear regression analysis showed that only the course of disease had a significant effect on clinical outcome,which was negatively correlated with the results (t =-7.082,P ＜ 0.001).The remaining variables including gender,age of onset,age of surgery,DBS target and preoperative movement score had no effect on clinical efficacy (all P ＞ 0.05).Conclusions DBS treatment of PGD is effective.Both GPi and STN can be used as alternative therapeutic targets and their efficacies seem similar.Patients with shorter disease duration may achieve better clinical outcomes.

Background Deep brain stimulation (DBS) is currently used to treat addiction, with the nucleus accumbens (NAc) as one promising target. The anterior limb of the internal capsule (ALIC) is also a potential target, as it carries fiber tracts connecting the mesocorticolimbic circuits that are crucially involved in several psychiatric disorders, including addiction. Stimulating the NAc and ALIC simultaneously may have a synergistic effect against addiction. Methods Eight patients with a long history of heroin use and multiple relapses, despite optimal conventional treatments, were enrolled. Customized electrodes were implanted through the ALIC into the NAc, and deep brain stimulation (DBS) treatment began two weeks after surgery. The patients were followed for at least 24 months. The duration of drug-free time, severity of drug cravings, psychometric evaluations, and PET studies of glucose metabolism before and after DBS were conducted. All adverse events were recorded. Results With DBS, five patients were abstinent for more than three years, two relapsed after abstaining for six months, and one was lost of follow-up at three months. The degree of cravings for drug use after DBS was reduced if the patients remained abstinent (p < 0.001). Simultaneous DBS of the NAc and ALIC also improved the quality of life, alleviated psychiatric symptoms, and increased glucose metabolism in addiction-related brain regions. Moreover, stimulation-related adverse events were few and reversible. Conclusions Simultaneous DBS of the NAc and ALIC appears to be safe, with few side effects, and may prevent long-term heroin relapse after detoxification in certain patients. (This trial was registered at ClinicalTrials.gov, NCT01274988).

OBJECTIVE: To evaluate the clinical effect of the position of stimulation contacts relative to the hyperdirect pathway (HDP) on the alleviation of motor symptoms in patients with Parkinson disease (PD). METHODS: A group of 11 patients diagnosed with idiopathic PD were included in this study, and all selected targets were in the subthalamic nucleus (STN). In 1 patient, a single side electrode was implanted because of unilateral symptoms; in all other patients, bilateral electrodes each containing 4 discrete contacts were implanted. Nine contacts were excluded due to adverse reactions caused by stimulation, and thus a total of 75 active contacts were evaluated using the same stimulus parameters. Fiber tractography results were individually processed using StealthViz software before all data were subjected to statistical analysis. RESULTS: Under the same stimulus parameters, the shortest distance of each contact to the HDP was smaller in group I (n = 45; >50% improvement rate) compared with group II (n = 30; <= 50% improvement rate) (mean, 1.18 +/- 0.86 mm vs. 2.14 +/- 1.20 mm; t = 3.78; P < 0.05), and the shortest distance had a negative correlation with the improvement of motor symptoms (r = L0.48; P < 0.05). CONCLUSIONS: Stimulation of the HDP coincided with the improvement of motor symptoms in patients with PD. We propose an improvement of the direct visualization method based on diffusion tensor imaging fiber tractography of the HDP to select the motor part of the STN. Further rigorous clinical trials are needed to verify the value of this method for achieving precise target location and individualized treatment.