Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by bradykinesia, rigidity, and tremor. However, familial PD caused by single-gene mutations remain relatively rare. Herein, we described a Chinese family affected by PD, which associated with a missense heterozygous glucocerebrosidase 1 (GBA1) mutation (c.231C > G). Clinical data on the proband and her family members were collected. Brain MRI showed no difference between affected and unaffected family members. Whole-exome sequencing (WES) was performed to identify the pathogenic mutation. WES revealed that the proband carried a missense mutation (c.231C > G) in GBA1 gene, which was considered to be associated with PD in this family. Sanger sequencing and co-segregation analyses were used to validate the mutation. Bioinformatics analysis indicated that the mutation was predicted to be damaging. In vitro functional analyses were performed to investigated the mutant gene. A decrease in mRNA and protein expression was observed in HEK293T cells transfected with mutant plasmids. The GBA1 c.231C > G mutation caused a decreased GBA1 concentration and enzyme activity. In conclusion, a loss of function mutation (c.231C > G) in GBA1 was identified in a Chinese PD family and was confirmed to be pathogenic through functional studies. This study help the family members understand the disease progression and provide a new example for studying the pathogenesis of GBA1-associated Parkinson disease.

目的 观察早期应用丁苯酞联合低分子肝素、双联抗血小板聚集药物治疗急性穿支动脉病变型脑梗死的疗效及安全性.方法 503例急性穿支动脉病变型脑梗死患者,随机分为对照组(253例)和研究组(250例).对照组患者给予低分子肝素、双联抗血小板聚集药物进行治疗,研究组在对照组基础上给予丁苯酞进行治疗.观察比较两组患者治疗前和治疗1、7 d后神经功能缺损程度,治疗前和治疗3个月后生活能力,不良反应发生情况.结果 两组患者治疗1、7 d后美国国立卫生研究院卒中量表(NIHSS)评分均低于本组治疗前,差异具有统计学意义(P<0.05).治疗1 d后,研究组NIHSS评分(14.63±1.34)分略低于对照组的(14.77±1.48)分,但差异无统计学意义(P>0.05);治疗7 d后,研究组患者NIHSS评分(8.03±1.54)分明显低于对照组的(11.56±2.01)分,差异具有统计学意义(P<0.05).两组患者治疗3个月后改良RANKIN量表(mRS)评分均低于本组治疗前,差异具有统计学意义(P<0.05).治疗3个月后,研究组患者mRS评分(0.98±0.34)分明显低于对照组的(1.77±0.48)分,差异具有统计学意义(P<0.05).两组患者治疗过程中均无肠道出血等不良反应发生.结论 早期应用丁苯酞联合低分子肝素、双联抗血小板聚集药物治疗急性穿支动脉病变型脑梗死患者,可有效改善患者的神经功能损伤状态,恢复患者生活能力,且安全性较好,具有较高的推广价值.

Alpha6-containing nicotinic acetylcholine receptors are primarily found in neurons of the midbrain dopaminergic (DA) system, suggesting these receptors are potentially involved in drug reward and dependence. Here, we report a novel effect that cocaine directly inhibits α6N/α3Cβ2β3-nAChR (α6*-nAChRs) function. Human α6*-nAChRs were heterologously expressed within cells of the SH-EP1 cell line for functional characterization. Mechanically dissociated DA neurons from mouse ventral tegmental area (VTA) were used as a model of presynaptic α6*-nAChR activation since this method preserves terminal boutons. Patch-clamp recordings in whole-cell configuration were used to measure α6*-nAChR function as well as evaluate the effects of cocaine. In SH-EP1 cells containing heterologously expressed human α6*-nAChRs, cocaine inhibits nicotine-induced inward currents in a concentration-dependent manner with an IC50 value of 30 μM. Interestingly, in the presence of 30 μM cocaine, the maximal current response of the nicotine concentration-response curve is reduced without changing nicotine’s EC50 value, suggesting a noncompetitive mechanism. Furthermore, analysis of whole-cell current kinetics demonstrated that cocaine slows nAChR channel activation but accelerates whole-cell current decay time. Our findings demonstrate that cocaine-induced inhibition occurs solely with bath application, but not during intracellular administration, and this inhibition is not use-dependent. Additionally, in Xenopus oocytes, cocaine inhibits both α6N/α3Cβ2β3-nAChRs and α6M211L/α3ICβ2β3-nCAhRs similarly, suggesting that cocaine may not act on the α3 transmembrane domain of chimeric α6N/α3Cβ2β3-nAChR. In mechanically isolated VTA DA neurons, cocaine abolishes α6*-nAChR-mediated enhancement of spontaneous inhibitory postsynaptic currents (sIPSCs). Collectively, these studies provide the first evidence that cocaine directly inhibits the function of both heterologously and naturally expressed α6*-nAChRs. These findings suggest that α6*-nAChRs may provide a novel pharmacological target mediating the effects of cocaine and may underlie a novel mechanism of cocaine reward and dependence.

Objective To investigate the role of network platform for treatment and rescue of acute and severe cerebrovascular diseases in improving treatment level of patients with acute ischemic stroke.Methods The differences of number of patients accepted venous thrombolysis, number of patients accepted emergency intravascular interventional treatment, and time from admission to intravenous thrombolysis (door to needle time [DNT]) were analyzed in patients with acute ischemic stroke admitted to our hospital in the first year (2016) and the second and third years (2017 and 2018) of construction of network platform for treatment and rescue of acute and severe cerebrovascular diseases in Yunfu city. The National Institutes of Health Stroke Scale (NIHSS) scores were compared in 120 patients selected randomly from online referral (study group,n=60) and non-online referral (control group,n=60) within the same time periods in 2018.Results In 2017 and 2018, the number of patients accepted intravenous thrombolysis was 85 and 103, respectively, and the rate of intravenous thrombolysis was 9.92％ and 9.83％; they were all significantly larger/higher than those in 2016 (n=50, 6.97％,P<0.05). In 2017 and 2018, the number of patients accepted emergency endovascular treatment was 56 and 129, respectively, and the emergency endovascular treatment rate was 6.53％ and 12.31％; they were all higher&nbsp;than those in 2016 (n=44 and 6.14％), and the differences between those in 2018 and 2016 were statistically significant (P<0.05). The DNT ([82.00±18.75] min in 2017 and [77.00±32.17] min in 2018) was significantly shorter than that in 2016 ([109.00±30.58] min,P<0.05). The NIHSS scores of the study group and control group were 4.70±3.64 and 8.90±5.62, respectively, after one week of treatment, both of which were lower than those before treatment (14.30±6.29 and 13.60±6.37); and after treatment, the NIHSS scores of the treatment group were statistically lower than those of the control group (P<0.05). Conclusion Construction and effective operation of network platform for treatment and rescue of acute and severe cerebrovascular diseases is an effective guarantee to improve the success rate of treatment for patients with acute ischemic stroke.

目的:探讨超时间窗急性前循环脑梗死患者血管内治疗的临床特点及疗效.方法:回顾性分析2017年1月至2019年1月云浮市人民医院收治的超时间窗急性前循环脑梗死患者的临床资料,所有患者均接受血管内治疗.所有患者进行TOAST分型和美国国立卫生研究院卒中量表(NIHSS)评分,术前基于CT平扫(NC-CT)进行阿尔伯特卒中项目早期CT评分(ASPECTS).出院后随访,行改良Rankin评分(mRS).结果:共10例患者纳入本研究,其中男7例、女3例,TOAST分型均为大动脉粥样硬化型,术前NIHSS评分均大于7分、ASPECTS评分大于5分.术后随访显示,7例ASPECTS评分大于7分的患者出院后3个月mRS评分为0～1分;3例ASPECTS评分为5～6分的患者出院后3个月mRS评分为4～5分.结论:基于NC-CT的ASPECTS评分大于7分的超时间窗急性前循环脑梗死患者进行血管内治疗可能获益.

目的:分析丁苯酞软胶囊、阿托伐他汀钙片对脑梗塞的治疗效果、侧支循环建立的影响.方法:研究阶段为2018年1月-2019年6月,共纳入研究对象87例,均为脑梗塞患者,随机分为两组,对照组采用阿托伐他汀钙片治疗,观察组采取丁苯酞软胶囊联合阿托伐他汀钙片治疗,比较两组临床效果.结果:对照组总有效率明显低于观察组(80.95％ vs 93.33％,P＜0.05).两组治疗前缺血区域血流量差异无统计学意义(P＞0.05),观察组治疗4周、8周后缺血区域血流量明显高于对照组(P＜0.05).结论:针对脑梗塞患者在常规对症治疗基础上采取丁苯酞软胶囊联合阿托伐他汀钙片治疗可有效提高治疗效果,实现侧支循环的建立,值得临床应用与推广.

目的 研究轻型脑梗死患者行静脉溶栓治疗的疗效及安全性,同时比较阿替普酶与尿激酶静脉溶栓疗效及安全性.方法 采用前瞻性研究方法,收集我科130例起病在6h内美国国立卫生研究院卒中量表(NIHSS)评分≤5分的轻型脑梗死患者的临床资料,其中治疗组41例,29例接受rt-PA静脉溶栓治疗,12例接受尿激酶静脉溶栓治疗;对照组89例接受常规治疗,通过分析患者溶栓后24h、3d、7d NIHSS和90d和180d的mRS评分及治疗期间的出血、纤维蛋白原减少、病情进展、死亡等不良事件,评估治疗方案的有效性和安全性.结果 治疗组患者24h、3d、7d后NIHSS评分均低于对照组,差异有统计学意义(P<0.05);治疗组90d、180d mRS评分也均低于对照组,差异有统计学意义(P<0.05).安全性方面治疗组轻型出血3例(1例为rt-PA,2例为尿激酶),溶栓后纤维蛋白原低于0.7g/L的有7例(rt-PA静脉溶栓1例,尿激酶溶栓6例),无死亡病例.对照组无出血、死亡,但出现脑梗死进展12例.结论 轻症脑梗死接受静脉溶栓治疗有效和相对安全,但对比尿激酶rt-PA静脉溶栓更为安全.

目的:监控缺血性脑卒中关键医疗质量指标(KPI)提高缺血性卒中医疗质量.方法:参照2007年国家卫生部制定的缺血性脑卒中/脑梗塞的质控指标及美国2003年开展一项大型研究"跟着指南走-卒中(Get With The Guideline-Stroke)"中的KPI,按照纳入标准收集2015年8月至2016年8月KPI,将之与我院2011年1月至2012年1月数据纵向比较,并与2012年华侨医院、2012-2013 CNSR及2009 GWTG相关数据横向比较.结果:纳入患者342名,溶栓人次、出院抗栓、出院降脂明显提高,但和美国相应指标比较仍然存在很大差距.结论:通过监控KPI可以提高缺血性卒中医疗质量.

目的:探讨应用氟哌噻吨美利曲辛治疗抑郁症疗效及脑电图变化.方法:选取我院收治的抑郁症患者140例,按随机数字表法分组,对照组70例予以谷维素、七叶神安片等一般药物治疗,研究组70例在一般药物治疗基础上予以氟哌噻吨美利曲辛治疗,比较两组汉密尔顿抑郁量表(HAMD)评分、抑郁自评量表(SDS)评分、健康调查问卷(SF-36)评分、脑电图异常率、临床疗效及不良反应发生率.结果:对照组有效率(57.14％)低于研究组(82.86％),差异具有统计学意义(P<0.05);与对照组比较,研究组治疗后HAMD评分、SDS评分较低,SF-36评分较高,治疗后脑电图异常率较低,差异具有统计学意义(P<0.05);治疗中发生的不良反应为头晕头痛、震颤、睡眠障碍、口干,两组不良反应发生率无显著差异(P>0.05).结论:氟哌噻吨美利曲辛治疗抑郁症的临床疗效确切,能有效改善抑郁状态,提高生活质量,降低脑电图异常率,具有较高的安全性.

目的:探讨云浮市区急性缺血性卒中患者超早期溶栓治疗院前、院内延误的影响因素.方法:以2015年01月至2016年12月我院收治的418例急性缺血性卒中患者基本资料为依据,以症状发生后3 h内是否入院治疗为标准,将其分为及时治疗组和延误治疗组,进行对比分析.结果:共304例符合研究要求,其中及时治疗组109例(35.9％),延误治疗组195例(64.1％);两组患者性别、年龄无明显差异(P>0.05),及时治疗组在对美国国立卫生研究院卒中量表(NIHSS)评分、对脑卒中的认识、溶栓治疗的知晓、发病时有旁观者,就医转运方式的比例均显著高于延误治疗组(P<0.01).患者到院后,超早期接受rt-PA溶栓78例,平均到院至溶栓时间(DNT)109 min(最短47 min),存在有呼叫会诊、接受CT检查、检验报告发出等流程方面的延误.结论:目前急性缺血性卒中的治疗存在明显延误的情况,应结合延误原因,进行针对性强化.

Cannabis sativa (marijuana) is a fibrous flowering plant that produces an abundant variety of molecules, some with psychoactive effects. At least 4% of the world's adult population uses cannabis annually, making it one of the most frequently used illicit drugs in the world. The psychoactive effects of cannabis are mediated primarily through cannabinoid receptor (CBR) subtypes. The prevailing view is that CB1Rs are mainly expressed in the central neurons, whereas CB2Rs are predominantly expressed in peripheral immune cells. However, this traditional view has been challenged by emerging strong evidence that shows CB2Rs are moderately expressed and function in specific brain areas. New evidence has demonstrated that brain CB2Rs modulate animal drug-seeking behaviors, suggesting that these receptors may exist in brain regions that regulate drug addiction. Recently, we further confirmed that functional CB2Rs are expressed in mouse ventral tegmental area (VTA) dopamine (DA) neurons and that the activation of VTA CB2Rs reduces neuronal excitability and cocaine-seeking behavior. In addition, CB2R-mediated modulation of hippocampal CA3 neuronal excitability and network synchronization has been reported. Here, we briefly summarize recent lines of evidence showing how CB2Rs modulate function and pathophysiology in the CNS.

Background Although rare, brain abnormalities without optic neuritis (ON) or transverse myelitis (TM) diagnosed with neuromyelitis optica spectrum disorder (NMOSD) have been reported in patients positive for the aquaporin-4 (AQP4) antibody. Objective To analyze demographic and clinical differences among NMOSD patients without ON or TM, those with either ON or TM, and patients with simultaneous ON and TM at disease onset. Methods In this retrospective study, patients who were positive for the AQP4 antibody, as detected using a cell-based assay, at the Second Affiliated Hospital of Guangzhou Medical University in China were recruited. Demographic and clinical data were obtained from each patient’s medical record. Results A total of 292 patients were included in this study and were divided into four subgroups based on their initial manifestations: (i) NMOSD without ON or TM (NMOSD-ON−TM−, n = 70); (ii) NMOSD with ON (NMOSD-ON+, n = 95); (iii) NMOSD with TM (NMOSD-TM+, n = 116); and (iv) simultaneous ON and TM [neuromyelitis optica (NMO), n = 11]. We found that age at onset was lower in the NMOSD-ON−TM− group than that in the other groups. The interval from the first episode to relapse was shorter in the NMOSD-ON−TM− group than that in NMOSD-TM+ group. Cerebral spinal fluid white cell counts and protein levels were significantly higher in the NMOSD-ON−TM− group than those in the other groups. Lower Expanded Disability Status Scale scores were observed in the NMOSD-ON−TM− group. Brain abnormalities, including in area postrema and hemisphere lesions, were more frequent in the NMOSD-ON−TM− group. Kaplan–Meier analysis showed that patients in the NMOSD-ON−TM− group experienced earlier relapse than those in other groups. Conversion to NMO in the NMOSD-ON+ group was greater than that in the other groups. Only 14 patients (4.8%, 14/292) had pure brain abnormalities, of which 12 had disease duration of several more years and 8 (57.1%) experienced relapses. Conclusion NMOSD patients with different initial manifestations present with significant differences in clinical features during follow-up. Patients with long-term AQP4 autoimmunity in the brain in the absence of ON or TM are not common.

目的 比较阿替普酶与尿激酶静脉溶栓治疗急性脑梗死的疗效及安全性.方法 111例急性脑梗死患者,根据所用静脉溶栓治疗药物不同分为阿替普酶组(采用阿替普酶静脉溶栓,67例)和尿激酶组(采用尿激酶静脉溶栓,44例).比较两组患者的临床疗效及安全性.结果 治疗后3 h、24 h、7 d、2周,两组患者美国国立卫生研究院卒中量表(NIHSS)评分均显著低于本组治疗前,且阿替普酶组NIHSS评分均低于尿激酶组,差异具有统计学意义(P<0.05).治疗3个月后,阿替普酶组预后良好患者42例(62.69%),与尿激酶组的28例(63.64%)比较差异无统计学意义(χ2=0.01,P>0.05).治疗后,阿替普酶组患者溶栓后纤维蛋白原<0.7 g/L有2例(2.99%),少于尿激酶组的7例(15.91%),差异具有统计学意义(χ2=5.95,P<0.05);阿替普酶组患者并发症发生率为5.97%,明显低于尿激酶组的20.45%,差异具有统计学意义(χ2=5.39,P<0.05);阿替普酶组死亡率1.49%低于尿激酶组6.82%,但差异无统计学意义(χ2=2.17,P>0.05).结论 治疗急性脑梗死患者,阿替普酶在溶栓后2周内疗效优于尿激酶,但两者治疗3个月后的神经功能恢复状况相当,且阿替普酶并发症少,死亡率低,相对较安全.

目的:探讨假性甲状旁腺功能减退症(PHP)的临床特征和伴发症状.方法:回顾性分析假性甲状旁腺功能减退症病例的资料,从临床表现、血生化结果、影像学结果等阐述假性甲状旁腺功能减退症的诊治方法.结果:假性甲状旁腺功能减退症是一种具有以低钙血症和高磷血症为特征的显性遗传性疾病,典型患者可伴有发育异常、智力发育迟缓、体态矮小肥胖、脸圆、并见掌骨及跖骨缩短,特别是对称性第四与第五掌骨缩短等.头颅CT容易发现异位钙化表现.脑电图可出现癫痫样波形.本病的治疗为纠正低钙高磷状态,控制癫痫发作.结论:以抽搐为首发症状、伴低血钙、高血磷生化表现,同时有异位钙化影像表现的病例,可能为假性甲状旁腺功能减退症.

目的:探讨假性甲状旁腺功能减退症(PHP)的临床特征和伴发症状。方法:回顾性分析假性甲状旁腺功能减退症病例的资料,从临床表现、血生化结果、影像学结果等阐述假性甲状旁腺功能减退症的诊治方法。结果:假性甲状旁腺功能减退症是一种具有以低钙血症和高磷血症为特征的显性遗传性疾病,典型患者可伴有发育异常、智力发育迟缓、体态矮小肥胖、脸圆、并见掌骨及跖骨缩短,特别是对称性第四与第五掌骨缩短等。头颅CT容易发现异位钙化表现。脑电图可出现癫痫样波形。本病的治疗为纠正低钙高磷状态,控制癫痫发作。结论:以抽搐为首发症状、伴低血钙、高血磷生化表现,同时有异位钙化影像表现的病例,可能为假性甲状旁腺功能减退症。

Background: High-dose methylprednisolone (MP) is a clinically recommended therapeutic regimen for Multiple Sclerosis (MS), whereas some dreadful complications induced by it remain inevitable. Studies implied that estrogens might play neuroprotective and anti-inflammatory roles in EAE and MS and promote glucocorticoid efficacy. Icariin (ICA), a primary active component of Epimedium extracts, also possesses neuroprotective and estrogen-like effects with less adverse complication than estrogen. However, rare study focuses ICA's effects on MS or EAE. Objective: Our purpose is to determine whether ICA has synergistic effects with MP in treating EAE and explore the possible mechanisms. Methods: C57BL/6 EAE mice were received different dose of ICA combined with MP and single MP treatment. Then, the clinical scores and serum Interleukin-17 (IL-17), Corticosterone (CORT), Adrenocorticotropic Hormone (ACTH) concentrations were analyzed. Western blot and Flow Cytometry were used to investigate the expression of glucocorticoid receptor (GR) and cell apoptosis. Results: ICA has cooperative effects with MP in decreasing serum IL-17 and CORT concentrations, up-regulating the expression of GR in cerebral white matter and attenuating the cell apoptosis in spinal cord, especially high-dose ICA combined with MP. Conclusion: ICA has synergistic effects with MP to ameliorate EAE via modulating hypothalamic-pituitary-adrenal (HPA) function, promoting anti-inflammatory and anti-apoptotic effects. ICA could be considered as a promising therapeutic option for MS.

目的探讨肝豆状核变性（HLD）患者的个性特点及不同人格类型患者的心理状况。方法 68例住院HLD患者采用艾森克个性问卷（EPQ）进行测查,根据结果分为外向-情绪稳定、外向-情绪不稳定、内向-情绪稳定、内向-情绪不稳定四个人格类型,与60例正常人的心理测查结果进行对照,并比较各人格类型的症状自评量表（Scl-90）。结果 HLD患者组外向-情绪不稳定型性格比例为52.9%,多于健康对照组（P＜0.00）;外向-情绪稳定型及内向-情绪稳定型性格的比例分别为19.1%、11.8%,少于健康对照组（P＜0.05）;内向-情绪不稳定型性格比例为16.2%,与健康对照组比较差异无统计学意义（P＞0.05）。HLD患者外向-情绪不稳定型及内向-情绪不稳定型性格者的敌对、偏执因子均分较外向-情绪稳定、内向-情绪稳定型性格者高（P＜0.05）。结论 HLD患者的个性特点以外向-情绪不稳定型为主。根据基因突变类型给予不同心理干预措施以及尽早介入心理干预,可能有助于对其良好人格特征的塑造并提高治疗效果。

Objective To investigate the correlation of transforming growth factor(TGF)-β1 T869C gene polymorphism with lacunar infarction(LI). Methods The genotyes of TGF-β1 T869C gene were determined by PCR-based assay in 143 patients with LI and 138 healthy controls. Results The frequency of T869C C allele was significantly higher in the LI group than that in the healthy controls(P = 0.002). The distribution of T869C polymorphism demonstrated that LI patients had higher TGF-β1 T869C CC frequency comparing with that in the healthy controls(P = 0.004). Conclusion The TGF-β1 T869C gene polymorphism is associated with LI, TGF-β1 T869C C allele may be an independent risk factor for LI.

This study aimed to identify aberrant transcripts of the new splice-site mutation c.3244-2A>C in the Wilson disease (WD) gene (ATPase, Cu++ transporting, beta polypeptide, ATP7B) and discuss its genotype and clinical phenotype. DNA and RNA were extracted from peripheral blood lymphocytes, amplified by polymerase chain reaction (PCR) and nested reverse transcription PCR (RT-nested PCR) to characterize the aberrant transcripts. RT-nested PCR product sequencing comparison showed that c.3244-2A>C splice-site mutation caused aberrant transcripts and formatted a new splice acceptor. Patient carrying the splice-site mutation c.3244-2A>C presented early onset age, severe clinical manifestations, and poor prognosis. WD patients with the splice-site mutation show severe clinical manifestations, indicating that aberrant transcripts have important implications for WD phenotype.

Objective:To study the related factors affecting mental health of patients with wilson disease ( WD) .Methods:We used Eysenck Personality Questionnaire ( EPQ ) , Unified Wilson's Disease Rating Scale ( UWDRS ) , Nazer Scale , Social Support Rating Scale(SSRS) and Symptom Checklist 90 (Scl-90) to investigate 82 patients with WD and recorded their basic clinical data as well as head imaging changes .The factors which may affact its mental health were analyzed .Results:The prevalence rates of psychological dis-order of the patients with WD was 46.3%.Their mental health was related to the neuroticism , degree of neurologic lesion , degree of liver lesion, social support and imaging range of intracranial lesions .Neurologic lesion(OR=8.708) and imaging range of intracranial lesions (OR=4.889) were independent Ly related factors in multiariable Logistic regression analysis .Conclusion:To reduce the neu-rologic lesion and restore the function of neurologic can improve the mental health of patient with WD .