Peripheral immunity and neuroinflammation interact with each other and they play important roles in the pathophysiology of idiopathic Parkinson’s disease (IPD). There have been very few real-world reports on the relationship between peripheral immune inflammation and motor phenotypes of IPD. This study aimed to investigate the potential correlation between peripheral inflammatory indicators and motor subtypes in patients with IPD. This observational, prospective case-control study examined patients with IPD and healthy controls (HC) matched for age and sex between September 2021 and July 2023 at the Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University. The levels of peripheral inflammatory indicators were collected from each patient with IPD and HCs. Differences in the levels of peripheral inflammatory indicators among groups were compared. Binary logistic regression analysis was used to explore the inflammatory mechanism underlying the motor subtype of IPD. A total number of 94 patients with IPD were recruited at the Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University between September 2021 and July 2023, including 49 males and 45 females, and 37 healthy volunteers matched for age and sex were also enrolled as the control group. Of the 94 patients with IPD, 42.6

BACKGROUD:Fatigue is one of the most common non-motor symptoms among patients with Parkinson's disease (PD).However, the pathogenesis keeps largely unknown. Moreover, it is lack of objective biomarker.OBJECTIVE:To investigate the relationship between plasma inflammatory cytokines and α-syn levels and fatigue in patients with PD.METHODS:A total of 63 PD patients were enrolled, including 35 patients with fatigue and 28 patients without fatigue. We compared the difference between plasma cytokines and alpha-synuclein (α-syn) in the two groups. Meanwhile, we analyzed the relationship between plasma cytokines and p-α-syn levels and fatigue.RESULTS:PD patients with fatigue had older age, longer disease duration, more severe motor scores. There were significant differences in the plasma levels of IL-1β, IL-18, TNF-α, and phosphorylated α-syn (p-α-syn) between the two groups. The plasm inflammatory cytokine levels (IL-1β, IL-18 and TNF-α) were positively associated with FSS scores. Moreover, the plasma p-α-syn level was significantly positively correlated with FSS scores. Furthermore, the higher PDQ-39 scores and higher plasma levels of TNF-α and p-α-syn were strongly associated with fatigue in PD. The ROC curve analysis showed the AUC of TNF-α for fatigue in PD was 0.663 with a sensitivity of 65.71% and specificity of 67.86%, while the AUC of p-α-syn was 0.786 with a sensitivity of 74.29% and specificity of 64.29%. The combination of TNF-α and p-α-syn improves the AUC to 0.803 with a sensitivity of 88.57% and specificity of 64.29%.CONCLUSION:The high plasma levels of TNF-α and p-α-syn were strongly associated with fatigue in PD.

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.

Objective:To investigate the correlation between plasma glial fibrillary acidic protein (GFAP), total α-synuclein (α-syn), phosphorylated α-synuclein (p-α-syn) and the disease progression in patients with Parkinson disease(PD).Methods:Sixty-three patients with PD including the outpatients and inpatients from Department of Neurology of Huai'an First People's Hospital were continuously collected as a PD group, and 25 healthy people matched in age and sex were selected as a healthy control (HC) group at the same time. The plasma levels of GFAP, α-syn, and p-α-syn levels in the PD group and HC group were detected by ELISA. SPSS 25.0 software was used for statistical analysis. Mann-Whitney U test was performed to assess the differences of GFAP, α-syn and p-α-syn levels between the two groups, and the correlation between GFAP and α-syn and p-α-syn levels in PD group was examined by Spearman correlation analysis. The levels of GFAP, α-syn and p-α-syn in different Hoehn-Yahr(H-Y) stages of PD group were compared by Mann-Whitney U test and Spearman correlation analysis. Results:The levels of GFAP (0.80(0.62, 0.97)ng/mL, 0.54(0.27, 0.88)ng/mL, Z=-3.216, P=0.001), α-syn (3.93(3.16, 6.02)ng/mL, 2.67(1.74, 4.47)ng/mL, Z=-2.600, P=0.009), and p-α-syn (5.80(1.31, 15.62), 0.71(0.61, 0.83), Z=-6.607, P<0.001) in PD group were higher than those in HC group, and the difference was statistically significant. In PD group, there was a significant positive correlation between GFAP and α-syn ( r=0.442, P<0.001) and p-α-syn ( r=0.493, P<0.001). GFAP in the advanced PD group was higher than that in the early PD group, and the difference was statistically significant( P=0.039). There was no significant difference in α-syn and p-α-syn between different H-Y stages of PD patients( P>0.05). Plasma GFAP was positively correlated with H-Y stages ( r=0.277, P=0.018). Conclusion:The level of plasma GFAP in PD patients is positively correlated with disease progression, which can be used as a potential biomarker for PD disease assessment.

目的 探讨 2 型糖尿病(T2DM)患者线粒体呼吸链复合酶Ⅰ、Ⅱ、Ⅲ活性与疲劳之间的潜在关系.方法 选取 2022 年 1 月 1 日—2022 年 12 月 31 日于泗洪县第一人民医院就诊的 130 例T2DM患者作为研究对象,根据疲劳量表评分分为糖尿病无疲乏组和糖尿病疲乏组.采集患者的血样,进行常规的空腹血糖(FBG)、糖化血红蛋白(HbA1c)检测,分别使用辅酶Q10(CoQ10)酶联免疫试剂盒和线粒体呼吸链复合物活性定量检测试剂盒检测CoQ10 和呼吸链复合酶Ⅰ、Ⅱ、Ⅲ的活性.采用独立样本t检验、双相关Pearson检验、ROC曲线、二元logistic回归分析评估各项临床指标与糖尿病疲劳风险的相关性.结果 2 组患者FBG、HbA1c、24 h平均血糖(24 h MBG)及 24 h血糖标准差(24 h SDBG)和简单自测抑郁量表(PHQ-9)、广泛性焦虑量表(GAD-7)评分差异无统计学意义(P>0.05).疲乏组患者CoQ10 和线粒体呼吸链复合酶Ⅰ、Ⅱ、Ⅲ水平均低于无疲乏组患者(P<0.05).T2DM患者CoQ10 水平和线粒体呼吸链复合酶Ⅰ、Ⅱ、Ⅲ活性与疲劳量表评分呈负相关(r=-0.451～-0.906,P<0.05).性别(女性)、年龄(60～69 岁/70～79 岁)、病程(10～年)均为影响T2DM患者产生疲劳感的独立危险因素.结论 线粒体呼吸链复合酶Ⅰ、Ⅱ、Ⅲ活性降低与 T2DM 患者疲劳感产生密切相关,而且对T2DM患者疲劳感的产生具有预测价值.

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.