OBJECTIVE:Growing evidence supports the efficacy and safety of fecal microbiota transplantation (FMT) in treating Parkinson's disease (PD). Fecal microbiota are commonly transplanted via oral capsules, a nasojejunal tube, or colonoscopy, but freezing often decreases the diversity and viability of transplanted microbiota. This single-center, double-blind, randomized, placebo-controlled trial aims to explore the efficacy and safety of fresh FMT via colonoscopy in dealing with PD. METHODS:Thirty patients with mild-to-moderate PD (Hoehn-Yahr stage I-III) were randomly assigned into the FMT group (fresh FMT via colonoscopy) and placebo group (saline injection via colonoscopy) in a 1:1 ratio. Motor and non-motor symptoms, constipation, quality of life, cognitive function, emotional state and sleep quality were assessed using relevant scales. Fecal samples were harvested before and at 4, 8 and 12 weeks after treatment for metagenomic and metabolomics analyses. RESULTS:A total of 30 patients with mild-to-moderate PD were enrolled in the present study, involving 18 males and 12 females with a median age of 68 years, a median age of onset of 63.5 years, and a median disease duration of 3 years. At 12 weeks, scores of the UPDRS Ⅲ (group × time effect, B =  - 8.80 [-13.79, -3.81]), PAC-QOL (group × time effect, B =  - 29.67 [-45.35, -13.98]), UPDRS Ⅱ (group × time effect, B =  - 5.07 [-8.85, -1.28]), NMSS (group × time effect, B =  - 35.60 [-53.59, -17.61]), PDQ-39 (group × time effect, B =  - 17.80 [-28.21, -7.39]), HAMA (group × time effect, B =  - 1.66 [-2.92, -0.40]), and HAMD (group × time effect, B =  - 1.33 [-2.49, -0.16]) were significantly reduced in the FMT group, while CSBM per week (group × time effect, B = 3.03 [1.42, 4.63]) and the Bristol Stool Scale score (group × time effect, B = 1.95 [0.12, 3.79]) significantly increased (all P < 0.05). Significant alterations were seen in the gut microbiota and fecal metabolites in the FMT group. No adverse events were observed during the follow-up period. CONCLUSION:Fresh FMT via colonoscopy is a safe and well-tolerated procedure for treating mild-to-moderate PD. It effectively alleviates motor and non-motor symptoms, thus facilitating defecation and improving the quality of life. These effects can be maintained for a minimum of 12 weeks and may be attributed to the optimization of gut microbiota and fecal metabolites.

Background and purpose Multiple inflammatory biomarkers have been shown to predict symptomatic cerebral vasospasm (SCVS) and poor functional outcome in patients with aneurysmal subarachnoid hemorrhage. However, the impact of the low-grade inflammation (LGI) score, which can reflect the synergistic effects of five individual inflammatory biomarkers on SCVS and poor functional outcome on aneurysmal subarachnoid hemorrhage (aSAH), has not yet been well established. The aim of this study was to evaluate the impact of the LGI score on SCVS and poor functional outcome in aSAH patients. Methods The LGI score was calculated as the sum of 10 quantiles of each individual inflammatory biomarker. The association of the LGI score with the risk of SCVS and poor functional outcome was analyzed with multivariate logistical regression. Results A total of 270 eligible aSAH patients were included in this study: 74 (27.4%) had SCVS, and 79 (29.3%) had poor functional outcomes. After adjusting for confounders, a higher LGI score was revealed to independently predict SCVS (OR, 1.083; 95% CI, 1.011–1.161; P = 0.024) and poor functional outcome (OR, 1.132; 95% CI, 1.023–1.252; P = 0.016), and the second and third tertile group had higher risk of SCVS than lowest tertile group (OR, 2.826; 95% CI, 1.090–7.327; P = 0.033) (OR, 3.243; 95% CI, 1.258–8.358; P = 0.015). The receiver operating characteristic (ROC) curve uncovered the ability of the LGI score to distinguish patients with and without SCVS (area under the curve [AUC] = 0.746; 95% CI, 0.690–0.797; P < 0.001) and poor functional outcomes (area under the curve [AUC] = 0.799; 95% CI, 0.746–0.845; P < 0.001), the predictive value of LGI on SCVS and poor functional outcome is superior than PLT, NLR and WBC, but there was no statistical difference between LGI and CRP for predicting SCVS ( P = 0.567) and poor functional outcome ( P = 0.171). Conclusions A higher LGI which represents severe low grade inflammation status is associated with SCVS and poor functional outcome at 3 months after aSAH.

目的:研究骨转换标志物Ⅰ型胶原氨基端前肽(procollagen typeⅠN-terminal propeptide,PINP)、Ⅰ型胶原羧基端前肽(β-cross-linked ctelopeptide of type Ⅰ collagen,β-CTX)在帕金森病(Parkinson's disease,PD)并发骨质疏松中的预测价值.方法:纳入PD患者105例,根据是否合并骨质疏松分为骨质疏松组和非骨质疏松组,对所有患者检测25(OH)D、甲状旁腺激素、骨钙素、β-CTX、PINP等骨代谢指标,分析各指标与骨质疏松发生之间的关系.结果:①骨质疏松组少动强直型比例、女性比例、PINP、骨钙素、β-CTX水平均高于非骨质疏松组,骨质疏松组25(OH)D水平低于非骨质疏松组,差异均具有统计学意义;②相关分析结果显示PD患者骨质疏松发生与骨钙素(r=0.28,P=0.005)、β-CTX(r=0.36,P=0.001)、PINP(r=0.40,P＜0.001)均呈正相关,与25(OH)D(r=-0.30,P=0.002)、PINP/β-CTX(r=-0.56,P＜0.001)均呈负相关,差异具有统计学意义;③多因素二元Lo-gistic回归分析显示,25(OH)D(OR=0.95,95%CI:0.84～0.98,P=0.041)、PINP/β-CTX(OR=0.90,95%CI:0.83～0.98,P=0.017)是PD病合并骨质疏松的独立危险因素;④ROC曲线分析示25(OH)D联合PINP/β-CTX时ROC曲线下面积最大,AUC=0.82,灵敏性=0.80,特异性=0.84,P＜0.001.结论:血清25(OH)D水平及PINP/β-CTX比值与PD患者骨质疏松发生密切相关,在PD患者骨质疏松的发生中具有重要的预测价值,二者联合检测时诊断价值更高.

Background:The role of the microbiota-gut-brain axis in Parkinson's disease (PD) has received increasing attention. Although gender differences are known to an essential role in the epidemiology and clinical course of PD, there are no studies on the sex specificity of the microbiota-gut-brain axis in the development and progression of PD.Methods:Fresh fecal samples from 24 PD patients (13 males, 11 females) were collected for metagenomic sequencing. The composition and function of the gut microbiota were analyzed by resting-state functional magnetic resonance imaging (fMRI). Gender-dependent differences in brain ALFF values and their correlation with microbiota were further analyzed.Results:The relative abundance of Propionivibrio, Thermosediminibacter, and Flavobacteriaceae_noname was increased in male PD patients. LEfse analysis showed that Verrucomicrobial, Akkermansiaceae, and Akkermansia were dominant in the males. In female patients, the relative abundance of Propionicicella was decreased and Escherichia, Escherichia_coli, and Lachnospiraceae were predominant. The expression of the sesquiterpenoid and triterpenoid biosynthesis pathways was increased in male PD patients and was statistically different from females. Compared to the Male PD patients, female patients showed decreased ALFF values in the left inferior parietal regions, and the relative abundance of Propionivibrio was positively correlated with the regional ALFF values.Conclusion:Our study provides novel clinical evidence of the gender-specific relationship between gut microbiota alterations and brain function in PD patients, highlighting the critical role of the microbiota-gut-brain axis in gender differences in PD.

Objective To investigate the impact of human serum albumin (HSA) levels on symptomatic cerebral vasospasm (SCVS) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods We retrospectively reviewed the medical records. SCVS was defined as the development of a new neurological deterioration when the cause was considered to be ischemia attributable to vasospasm after other possible causes of worsening had been excluded. The aSAH patients were divided into two groups: those with SCVS (group 1) and those without SCVS (group 2). The HSA level data on the 1st, 2nd, and 3rd day after admission was collected. Multivariate logistical regression and receiver operating characteristic (ROC) analysis were performed to evaluate the ability of HSA level to predict the development of SCVS. Results A total of 270 patients were included in our study, of which 74 (27.4%) developed SCVS. The average and lowest HSA levels were lower in group 1 ( P < 0.001). In univariate logistic regression, white blood cell count, neutrophil count, and average and lowest HSA levels were associated with SCVS. After adjustment for age, CT Fisher grade, Hunt-Hess grade, and WFNS grade, both the average and lowest HSA levels remained independent predictors of SCVS ( P < 0.001). The CT Fisher grade was confirmed to be an independent predictor of SCVS across each model. ROC analysis revealed that the lowest HSA level was a better predictor for SCVS than average HSA level and CT Fisher grade. Conclusion Clinicians are encouraged to measure HSA levels for the first 3 days after admission to predict the occurrence of SCVS after aSAH.

目的 探讨帕金森病嗅觉识别障碍的临床特点及相关影响因素.方法 选取淮安市第一人民医院就诊的原发性PD患者54例,另同期健康检查的20名志愿者为对照组.采用PD嗅觉障碍(OD)辅助诊断卡对2组进行嗅觉识别功能评估,对比组间人口学资料、嗅觉得分及各气味选项正确率.根据嗅觉识别评分将PD患者分为PD伴OD(PD-OD)组和PD不伴OD(PD-NOD)组,对2组人口学资料、疾病分型及分期、非运动症状等临床资料进行比较,采用Logistic回归分析研究PD并发嗅觉识别障碍的危险因素.结果 PD组嗅觉得分明显低于对照组[5.0(4.0,8.0)分vs 9.0(8.0,9.0)分,P<0.05].PD组苹果(25.9％vs 85.0％,P<0.05)、玫瑰(24.1％vs 80.0％,P<0.05)、木头(44.4％vs 85.0％,P<0.05)、薄荷(29.6％vs 80.0％,P<0.05)气味选项的正确率较对照组降低.PD-OD组较PD-NOD组焦虑[(8.1±3.7)分vs(5.9±2.8)分,P<0.05]、抑郁[(7.6±3.6)分vs(5.4±3.0)分,P<0.05]、RBD[(5.6±2.7)分vs(3.9±2.1)分,P<0.05]、便秘评分[6.0(4.0,7.8)分vs 3.0(2.0,6.3)分,P<0.05]及PIGD亚型占比增高(45％vs 21.4％,P<0.05),PD-OD组较PD-NOD组焦虑(50％vs 14.3％,P<0.05)、便秘(70％vs 35.7％,P<0.05)、RBD(52.5％vs 21.4％,P<0.05)的发生率升高.Logistic回归显示疾病亚型、便秘及RBD是PD伴发嗅觉识别功能障碍的独立危险因素.结论 苹果、玫瑰、木头、薄荷气味用于评估PD嗅觉识别障碍具有优势,伴OD的PD患者更易出现便秘、焦虑、抑郁、RBD等非运动症状,便秘、疾病亚型、RBD是PD-OD的影响因素.

帕金森病是中老年患者常见的神经系统退行性疾病.嗅觉障碍、神经精神症状、睡眠障碍、自主神经功能障碍等非运动症状是帕金森病除静止性震颤、运动迟缓、肌强直、姿势平衡障碍等临床表现之外的另一组显著特征.其中嗅觉障碍可能是帕金森病最早出现和最常见的非运动症状之一.嗅觉检测可为帕金森病早期诊断和鉴别诊断提供依据.本文从帕金森病嗅觉障碍的病理生理机制、嗅觉检测方法、嗅觉检测在帕金森病鉴别诊断中的应用等方面作一综述.

自身免疫性胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)星形细胞病是一组累及脑膜、脑、脊髓及视神经的综合征,其影像学特点为侧脑室旁放射状线样强化病灶[1-2],该病于 2016 年由梅奥诊所首先报道并命名[3].近年来,该疾病的报道日益增多.现对南京医科大学附属淮安第一医院诊断的两例自身免疫性GFAP星形细胞病的临床资料总结并结合文献复习,以提高神经科医师对该病的认识.

目的 观察粪菌移植对帕金森病便秘患者心境及睡眠障碍的临床影响.方法 筛选2017年9月至2019年12月南京医科大学附属淮安第一医院神经内科收治的16例存在便秘、焦虑、抑郁和睡眠障碍的帕金森病患者,行粪菌移植治疗并随访12周,记录粪菌移植前后患者Wexner便秘评分量表(Wexner)、便秘患者生活质量量表(PAC-QOL)、匹斯堡睡眠质量指数量表(PSQI)、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)、帕金森病生活质量问卷(PDQ-39)评分并进行比较.结果 与治疗前比较,粪菌移植治疗后患者第4、8、12周的Wexner、PAC-QOL、PSQI、HAMD、HAMA和PDQ-39评分均明显下降(均P<0.01).结论 粪菌移植治疗可以显著改善帕金森病便秘患者的心境和睡眠障碍.

目的 系统评价嗅觉功能障碍与帕金森病(PD)认知功能的关系.方法 计算机检索中国知网、万方数据、中国生物医学文献数据库、PubMed、Embase、Cochrane Library和Web of Science数据库,搜集PD患者嗅觉功能障碍和认知功能关系的病例对照研究,检索从建库至2021年11月,依据纳入和排除标准筛选文献、质量评价后采用Revman 5.4软件及Stata 14进行Meta分析.结果 最终纳入10篇研究,共包括1 568名受试对象,其中嗅觉障碍组(PD-OD组)884例,嗅觉正常组(PD-NOD组)684例.与对照组相比PD-OD组认知评分更低[SMD=-0.45,95％CI(-0.62,-0.28),P＜0.01],在不同认知域得分比较中,与PD-NOD组相比,PD-OD组在记忆[SMD=-0.71,95％CI(-0.90,-0.51),P＜0.01]、执行[SMD=-0.46,95％CI(-0.80,-0.12),P＜0.01]、语言[SMD=-0.41,95％CI(-0.71,-0.11),P＜0.01]、注意与工作记忆[SMD=-0.27,95％CI(-0.48,-0.06),P＜0.01]、视空间功能[SMD=-0.45,95％CI(-0.78,-0.11),P＜0.01]五方面得分均较低.结论 PD患者认知功能下降与嗅觉功能障碍有关.在对PD患者实施促进认知功能的干预措施时应重点关注已出现嗅觉障碍的患者.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Patients with PD often suffer from gastrointestinal symptoms in the early stage of the disease. Several studies have confirmed that gut microbiota is involved in the progress of PD. As one of the most effective ways to reconstruct the gut microbiota, fecal microbiota transplantation (FMT) has shown potential therapeutic effects on PD. This review summarizes the basic and clinical studies of FMT in the treatment of PD.

目的 探究不同年龄后循环急性脑梗死患者阿替普酶静脉溶栓的疗效及安全性.方法 选取2017年2月至2020年3月在江苏省淮安市第一人民医院接受阿替普酶静脉溶栓治疗的150例后循环急性脑梗死患者,根据年龄分为A组(年龄<65岁)、B组(年龄65～80岁)、C组(年龄>80岁),各50例.比较3组患者治疗效果、疗效维持时间、治疗后不同时间美国国立卫生研究院卒中量表(NIHSS)评分、改良Rankin(mRS)评分、死亡情况和不良反应发生情况.结果 治疗后14 d,3组患者有效率组间差异无统计学意义(P>0.05).C组平均疗效维持时间长于A、B组[(8.3±2.4)d比(6.5±1.7)、(6.8±1.8)d],差异有统计学意义(P<0.05).C组治疗后1、7 d的NIHSS评分高于A、B组[(7.5±2.1)分比(6.1±1.7)、(6.3±1.8)分;(6.2±1.7)分比(5.2±1.4)、(5.1±1.3)分],差异均有统计学意义(均P<0.05).3组治疗后14、30 d的NIHSS和mRS评分差异均无统计学意义(均P>0.05).治疗14、30 d,3组病死率比较差异均无统计学意义(均P>0.05).3组不良反应发生率比较差异无统计学意义(P=0.726).结论 阿替普酶在>80岁的后循环急性脑梗死患者中应用的安全性和有效性较高,疗效维持时间长于年龄≤80岁的患者.

Parkinson’s disease (PD) is the most prevalent neurodegenerative movement diseases featured by selective loss of dopaminergic (DA) neurons within the striatum and substantia nigra (SN). Accumulating evidence have indicated that angiotensin-(1-7) (Ang-(1-7)) prevents neuronal damage by binding to its specific receptor Mas in PD. To date, the underlying mechanisms is not known thus far. In the present study, by using α-synuclein A53T transgenic mice (A53T mice), we showed that the neuronal apoptosis in the SN of A53T mice may be attributed to a decrease in Ang-(1-7) levels. Additionally, we revealed that AVE0991, a recently found non-peptide analogue of Ang-(1−7), ameliorated neuronal apoptosis via Mas/ERK pathway in primary DA neurons. More importantly, we provided novel evidence that this beneficial impact was dependent on the suppression of mitochondrial permeability transition pore opening. In conclusion, these findings disclose the neuroprotective impact of Ang-(1−7) in the etiology of PD, and support the application of its nonpeptide analogue AVE0991 in the therapies of this neurodegenerative disease.

Recent researches showed that nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome inhibition exerted dopaminergic neuroprotection in cellular or animal models of Parkinson’s disease (PD). NLRP3 inflammasome has been proposed as a drug target for treatment of PD. However, the interplay between chronic NLRP3 inflammasome and progressive α-synuclein pathology keeps poorly understood. Moreover, the potential mechanism keeps unknown. In the present study, we investigate whether NLRP3 inflammasome inhibition prevents α-synuclein pathology by relieving autophagy dysfunction in the chronic 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of PD. NLRP3 knockout mice and their wild-type counterparts were treated with continuous MPTP administration via osmotic mini-pumps. Dopaminergic neuronal degeneration was assessed by western blotting and immunohistochemistry (IHC). The levels of dopamine and its metabolites were determined using high-performance liquid chromatography. NLRP3 inflammasome activation and autophagy biomarkers were assessed by western blot. The expressions of pro-inflammatory cytokines were measured by ELISA. The glial reaction and α-synuclein pathology were assessed by IHC and immunofluorescence. Our results show that NLRP3 inflammasome inhibition via NLRP3 knockout not only protects against nigral dopaminergic degeneration and striatal dopamine deletion but also prevents nigral pathological α-synuclein formation in PD mice. Furthermore, it significantly suppresses MPTP-induced glial reaction accompanied by the secretion of pro-inflammatory cytokines in the midbrain of mice. Most importantly, it relieves autophagy dysfunction in the midbrain of PD mice. Collectively, we demonstrate for the first time that improving autophagy function is involved in the preventive effect of NLRP3 inflammasome inhibition on α-synuclein pathology in PD.

Imbalances in the gut microbiota mediate the progression of neurodegenerative diseases such as Parkinson's disease (PD). Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for PD. The objective of this study was to assess the efficacy and safety of FMT on PD. Fifteen PD patients were included, 10 of them received FMT via colonoscopy (colonic FMT group) and 5 received FMT via nasal-jejunal tube (nasointestinal FMT group). The score of PSQI, HAMD, HAMA, PDQ-39, NMSQ and UPDRS-III significantly decreased after FMT treatment (allP < .05). Colonic FMT group showed significant improvement and longer maintenance of efficacy compared with nasointestinal FMT (P = .002). Two patients achieved self-satisfying outcomes that last for more than 24 months. However, nasointestinal FMT group had no significant therapeutic effect, although UPDRS-III score slightly reduced. There were no patients were satisfied with nasointestinal FMT for more than 3 months. Among 15 PD patients, there were 5 cases had adverse events (AEs), including diarrhea (2 cases), abdominal pain (2 cases) and flatulence (1 case). These AEs were mild and self-limiting. We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable.

目的 探讨晚期前列腺癌患者经内分泌治疗后前列腺特异性抗原(PSA)的动态变化情况与疾病自身进展和生存预后情况的相关性.方法 检测46例晚期前列腺癌患者血清标本中PSA值,比较其变化水平与患者生存时间之间的关系.结果 PSA谷值<0.2 ng/mL患者的总生存率及疾病无进展生存率均明显高于PSA谷值≥0.2 ng/mL患者,差异有统计学意义(P=0.008;P=0.033).PSA达谷时间≥10个月患者总生存率及疾病无进展生存率均明显高于PSA达谷时间<10个月患者,差异有统计学意义(P<0.001;P<0.001).结论 PSA谷值、PSA达谷时间与患者的总生存率及疾病无进展生存率之间具有明显相关性,PSA动态变化可以预测晚期前列腺癌患者内分泌治疗的预后.

Objective To observe the safety and efficacy of fecal microbiota transplantation (FMT) in treatment of Parkinson′s disease (PD) with constipation. Methods From September 2017 to April 2019, 22 PD patients with serious constipation in the Department of Neurology, the Affiliated Huaian No. 1 People′s Hospital of Nanjing Medical University were treated with FMT and followed up for 12 weeks. Spontaneous bowel movement (SBM) per week and scores of Wexner Constipation Scale (Wexner), Constipation Quality of Life Scale (PAC-QOL) and Parkinson′s Disease Quality of Life Questionnaire (PDQ-39) were recorded before and after transplantation. Results Compared with the number of independent defecation and scores before treatment, the number of independent defecation per week (4.63± 2.25, 5.38 ± 1.23, 5.75 ± 1.29, 5.54 ± 1.30 vs 1.57 ± 0.74), Wexner score (7.92 ± 2.61, 5.67 ± 1.78, 5.08 ± 1.83, 4.92 ± 1.78 vs 16.67 ± 4.31), PAC-QOL score (62.3 ± 3.2, 58.8 ± 2.8, 57.1 ± 3.9, 59.6 ± 4.4 vs 110.3 ± 14.7) and PDQ-39 score (44.8 ± 14.8, 37.8 ± 12.8, 32.8 ± 12.3, 31.9 ± 9.2 vs 58.7 ± 16.7) were significantly improved by FMT treatment at two, four, eight and 12 weeks (P<0.01). After 12-week treatment, the effective rate was 100% (22/22), and the clinical cure rate was 86% (19/22). No serious adverse reactions occurred during treatment. Conclusion FMT is effective and safe in treating PD with constipation.

本病例急性起病,首诊被误诊为急性缺血性脑血管病,经皮肤活检和FMR1基因检测排除脆性X相关震颤/共济失调综合征(FXTAS)最终确诊为神经元核内包涵体病(NIID).通过对本病例资料的复习,可以加深对NIID的认识,提高临床对NIID的识别能力和鉴别诊断水平,避免误诊和漏诊.