Characterization of Streptococcus sanguis Isolated from Patients with Behçet's Disease

The DNA homology and cell wall sugar constituents of eight Streptococcus sanguis(-like) strains, three isolated from the patients with Behçet's disease (BD114-23, BD113-20, BD118-1), two from patients with Kawasaki disease (MCLS-1, MCLS-2), and three type and reference strains of ATCC (ATCC10556^T: S. sanguis, ATCC10557: S. oralis, and ATCC10558^T: S. gordonii) were analyzed. Strains BD114-23 and BD118-1 showed high DNA homology to ATCC10556^T, and their cell wall constituents were identical. Conversely, BD113-20, MCLS-1, MCLS-2, and ATCC10557 showed little DNA homology to ATCC10556^T and ATCC10558^T, but showed approximately 50 to 60% homology to each other. The cell wall constituents of BD113-20, MCLS-1, MCLS-2, and ATCC10557, however, were somewhat different, indicating that some of the clinical isolates have different characters from those of the three ATCC strains.     

Association of long non-coding RNAs NEAT1, and MALAT1 expression and pathogenesis of Behçet's disease among Egyptian patients

Behçet''s disease (BD) is a chronic inflammatory disease. Immunological defects have been shown to play a significant role in the progression of BD. The serum levels of two long non-coding RNAs (lncRNAs), NEAT1 and MALAT1, were examined in patients with BD to identify their role in the disease pathogenesis. Both lncRNAs were mentioned as essential regulators of innate immune responses and have a crucial role in inflammatory diseases. Fifty patients with BD and a similar number of control individuals were involved in our study. At enrollment, data was collected from patients and controls, and the disease severity in active cases was determined using the Behçet''s Disease Current Activity Form (BDCAF). Levels of the two studied biomarkers in the serum, NEAT1 and MALAT1, were investigated by quantitative RT-PCR (qRT-PCR). NEAT1 levels were significantly turned down in BD patients (fold changes = 0.77, p = 0.0001) and correlated negatively with the BDCAF (r = −0.41; p = 0.003). On the other hand, the MALAT1 levels were significantly up-regulated in BD patients (fold changes = 2.65, p = 0.003). Serum levels of NEAT1 were significantly decreased in patients with active states than in stationary cases (0.387 versus 1.99, respectively; p = 0.01) and compared with controls (p = 0.001). Also, NEAT1 levels were significantly increased in patients with stationary states compared to controls (p = 0.03). There was a positive association between NEAT1 and MALAT1 levels among BD patients (r = 0.29, p = 0.04). Our findings demonstrate a possible role of NEAT1 and MALAT1 in the pathogenesis of BD.     

Interleukin-6 in neuro-Behçet’s disease: Association with disease subsets and long-term outcome

Increased cerebrospinal fluid (CSF) IL-6 has been reported in patients with Behçet’s disease (BD) and neurological involvement. To elucidate the value of IL-6 as a marker of disease activity, serum and CSF IL-6 levels of 68 BD patients with acute (26) or chronic progressive (14) parenchymal involvement (pNB), dural sinus thrombosis (10), ischemic stroke (5) or headache (13) were measured by ELISA. Samples from multiple sclerosis, subacute sclerosing panencephalitis, and noninflammatory neurological disorders were used as controls. CSF but not serum samples of neuro-BD patients with acute pNB displayed significantly increased IL-6 levels as compared to other groups. Chronic progressive pNB patients also showed increased CSF IL-6 levels, albeit less prominent. Patients with increased CSF IL-6 levels were more likely to have increased CSF cell counts and total protein levels and these three parameters were correlated with long-term (3 years) disease outcome. In four chronic progressive patients, IL-6 was elevated despite otherwise normal CSF. CSF IL-6 seems to be a marker of disease activity and long-term outcome for pNB along with CSF cell count and protein levels. CSF IL-6 could be used in chronic progressive patients who have normal CSF cell, or protein levels to detect disease activity.     

Focus: Rare Disease: Behçet’s Disease and Pregnancy: A Retrospective Case-control Study

Background: Behçet’s disease (BD) is a rare chronic multisystemic vasculitis of unknown etiology. It is usually diagnosed between the 2^nd and 4^th decades of life, so its association with pregnancy is not unusual. This study aims to characterize the evolution of pregnancy in a group of pregnant women with BD and the impact of this pathology in embryo-fetal morbidity. Methods: A retrospective case-control study included 49 pregnancies in women suffering from BD, followed in our institution. Pregnancy outcomes were compared with a control group of healthy pregnant women. Two controls per case were randomly selected. Statistical analysis used SPSS 25.0, and a p-value of 0.05 was considered statistically significant. Results: Forty-nine pregnancies were included in 27 patients with BD. BD exacerbation occurred in 32.6% of the pregnancies. There were no significant statistical differences between the two groups regarding the rate of preterm delivery, gestational diabetes, and preeclampsia (p>0.05). In the BD group, we found a higher rate of miscarriage (24.5%) and fetal growth restriction (FGR, 13.3%, p<0.05). In the study group, 13 (32.5%) of the pregnant patients did not need treatment. The cesarean rate was significantly higher in the BD group (43.2% vs 20.4% in the control group, p<0.05), and there were no significant differences in median gestational age at the time of delivery (p>0.05). The birth weight of newborns did not differ significantly between the groups. There was no association of BD with maternal morbidity and neonatal complications. Conclusion: In this study, the majority of pregnant with BD did not present clinical exacerbation of their pathology. However, BD may have an adverse influence on pregnancy outcomes. FGR and miscarriage rates were significantly higher in the study group.     

帕金森病患者血浆alpha-synuclein、Abeta及tau蛋白变化特点

目的：探索帕金森病（Parkinson''s disease,PD）患者血浆中alpha- 突触核蛋白、Abeta及tau 蛋白变化情况。方法：募集2014 年4 月至 2015 年4 月来我院就诊的PD 患者62 例,正常对照人群59 例,采集两组人群的基本临床信息,测定血浆中琢- 突触核蛋白、 Abeta40、Abeta42、pT181-tau 蛋白、pT231-tau 蛋白和总tau 蛋白浓度,比较两组之间的差异,同时进行相关性分析。结果：PD患者血浆 alpha- 突触核蛋白和pT181-tau 蛋白浓度显著高于对照组(P 值分别为0.001,0.019),而两组间Abeta40、Abeta42、pT231-tau 蛋白和总tau 蛋白浓度无明显差异（P>0.05）。相关性分析提示PD 患者血浆alpha-突触核蛋白和pT181-tau 蛋白浓度与患者年龄、性别、教育程度、 病程、高血压、糖尿病、Hoehn/ Yahr 分级及Schwab &England 评分无相关性（P>0.05）。结论：虽然PD患者血浆琢- 突触核蛋白和 pT181-tau 蛋白高于正常对照组,但尚不适宜作为PD 的生物标志物。     

Approximating Exact Probabilities by χ2 and Continuity-Corrected χ2 in 2×2 Tables

Computations have been performed to find an adequate definition of exact two-sided probabilities in 2times2 contingency tables. It turns out, that both uncorrected χ² and Yates' correction for continuity give only unsatisfactory approximations to the exact probabilities of the hypergeometric distribution. The latter are therefore recommended for general use.     

A novel ATP7B gene mutation in a liver failure patient with normal ceruloplasmin and low serum alkaline phosphatase

Wilson's disease (WD) is a rare disorder of copper metabolism resulting in accumulation of copper in liver and other organs. We present a liver failure patient, who was misdiagnosed for two years, with normal ceruloplasmin and low serum alkaline phosphatase. Molecular testing revealed a novel p.Ala982Thr mutation within ATP7B gene. The pathology of liver sample showed a large amount of copper deposition in the hepatocytes and confirmed the diagnosis of WD. Our data highlighted the importance of molecular testing in the early diagnosis of atypical WD.     

帕金森病患者营养不良的影响因素分析及与衰弱、认知功能和跌倒风险的关系研究

摘要 目的：分析帕金森病（PD）患者营养不良的影响因素,并观察营养不良对衰弱、认知功能和跌倒风险的影响。方法：选取江苏省人民医院2019年3月至2022年3月期间收治的100例PD患者。采用简易营养评价量表（MNA）对研究对象进行营养状态评估,将100例患者分为营养不良组（n=52）和无营养不良组（n=48）。获取所有患者的一般资料,经Logistic回归分析PD患者营养不良的影响因素。同时对比无营养不良组、营养不良组的衰弱、认知功能和跌倒风险情况。结果：PD患者营养不良与年龄、体质量指数、Hoehn-Yahr分级、居住地、婚姻状况、血红蛋白、白蛋白、前白蛋白、每日左旋多巴等效剂量（LEDDs）、睡眠状况、焦虑状况、抑郁状况、味觉障碍、吞咽障碍、食欲下降有关（P<0.05）。Logistic回归分析,结果显示：年龄偏大、Hoehn-Yahr分级为III~V级、睡眠状况偏差、焦虑/抑郁状况严重、味觉障碍、吞咽障碍、食欲下降、LEDDs偏高是PD患者出现营养不良的危险因素（P<0.05）。营养不良组的衰弱发生率高于无营养不良组,衰弱前期、无衰弱发生率低于无营养不良组（P<0.05）。营养不良组的简易精神状态检查量表（MMSE）、蒙特利尔认知评估量表（MOCA）评分低于无营养不良组（P<0.05）。营养不良组的起立-行走计时测验（TUGT）时间、站起测验（CRT）时间长于无营养不良组,走直线步态测验（TGT）正确步数少于无营养不良组（P<0.05）。结论：PD患者营养不良发生风险较高,且受到年龄、睡眠状况、焦虑状况、抑郁状况、Hoehn-Yahr分级、味觉障碍、吞咽障碍、食欲下降、LEDDs的影响,且营养不良可加重衰弱、降低认知功能和增加跌倒风险。     

经颅直流电刺激对帕金森病伴快速眼动相睡眠行为障碍患者认知功能及神经功能的影响

摘要 目的：探讨经颅直流电刺激对帕金森病伴快速眼动相睡眠行为障碍患者认知功能及神经功能的影响。方法：选择2018年9月-2019年9月在我院接受治疗的69例帕金森病伴快速眼动相睡眠行为障碍患者,采用随机数表法分为电刺激组（n=35）和对照组（n=34）。对照组给予常规抗帕金森病治疗,观察组在对照组的基础上给予经颅直流电刺激治疗。比较两组临床疗效、蒙特利尔认知评估量表（MoCA）、自主神经症状量表（SCOPA-AUT）、睡眠情况、汉密尔顿抑郁量表(HAMD)、Epworth嗜睡量表（ESS）评分、匹兹堡睡眠指数（PSQI）、帕金森氏病综合评分量表（UPDRS）变化情况。结果：治疗后,电刺激组有效率91.43%（32/35）较对照组70.59%（24/34）显著升高,差异显著（P<0.05）;治疗前,电刺激组与对照组之间认知功能及神经功能结果无差异;治疗后,电刺激组与对照组MoCA均随着时间的推移均呈上升趋势,且电刺激组上升程度较较组更低,SCOPA-AUT均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间临床睡眠情况结果无差异;治疗后,电刺激组与对照组总睡眠时间、睡眠效率均随着时间的推移均呈上升趋势,且电刺激组上升程度较对照组更低,醒觉指数均随着时间的推移呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间抑郁、嗜睡情况无差异;治疗后,电刺激组与对照组抑郁、嗜睡均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间PSQI、UPDRS评分无差异;治疗后,电刺激组与对照组PSQI、UPDRS评分均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）。结论：在帕金森病伴快速眼动相睡眠行为障碍患者中应用经颅直流电刺激效果显著,可有效改善认知功能及神经功能水平。     

补肾活血疏肝汤联合西药治疗帕金森伴睡眠障碍及抑郁的疗效分析

目的:探讨补肾活血疏肝汤联合西药治疗帕金森(PD)伴睡眠障碍及抑郁的临床疗效。方法:选择2016年1月～2018年1月上海中医药大学附属第七人民医院神经内科收治的210例PD伴睡眠障碍及抑郁患者,根据随机数字表法将患者分为联合组和对照组,每组各105例。对照组采用常规西医治疗,治疗组在此基础上加用补肾活血疏肝汤。治疗3个月后,评价和比较两组的总体疗效、治疗前后UPDRSⅡ、Ⅲ评分、PSQI评分及HAMD评分的变化情况。结果:治疗后,联合组UPDRSⅡ、Ⅲ评分和HAMD评分均较治疗前显著下降,且明显低于对照组(P0.05);两组PSQI评分均较治疗前显著下降,且联合组PSQI评分显著低于对照组(P0.05)。结论:补肾活血疏肝汤联合西药治疗PD伴睡眠障碍及抑郁可显著提高其临床疗效,改善患者的睡眠障碍及抑郁状态。     

老年帕金森病患者睡眠障碍的危险因素及其对认知功能、心理状态和衰弱的影响

摘要 目的：探讨老年帕金森病（PD）患者睡眠障碍的危险因素,并观察睡眠障碍对认知功能、心理状态和衰弱的影响。方法：选取2018年3月~2021年9月期间中国人民解放军海军青岛特勤疗养中心收治的91例老年PD患者作为研究对象,根据是否存在睡眠障碍将入选的91例患者分为睡眠障碍组（n=56）及非睡眠障碍组（n=35）。采用蒙特利尔认知评估量表（MoCA）评估所有患者的认知功能状况。采用汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）评价患者焦虑、抑郁情况。采用Tilburg衰弱评估量表评估所有患者的衰弱情况。采用多因素Logistic回归分析探讨老年PD患者睡眠障碍的危险因素,并观察睡眠障碍对认知功能、心理状态和衰弱的影响。结果：睡眠障碍组的视空间与执行功能、语言、命名、延迟回忆、注意、抽象、定向评分及总分均低于非睡眠障碍组（P<0.05）。睡眠障碍组的HAMA、HAMD评分均高于非睡眠障碍组（P<0.05）。睡眠障碍组的心理衰弱、躯体衰弱、社会衰弱评分及总分均高于非睡眠障碍组（P<0.05）。多因素Losgistic回归分析结果显示：HAMA评分偏高、多巴丝肼片等效剂量偏高、HAMD评分偏高、Hcy偏高是老年PD患者睡眠障碍的危险因素（P<0.05）。结论：HAMA评分偏高、Hcy偏高、多巴丝肼片等效剂量偏高、HAMD评分偏高是老年PD患者睡眠障碍的危险因素。同时,睡眠障碍可加重老年PD患者的认知功能障碍和衰弱程度,增加抑郁焦虑情绪。     

肝豆汤联合驱铜治疗方案对湿热内蕴型肝豆状核变性患者肝脏代谢和认知功能的影响

摘要 目的：探讨肝豆汤联合驱铜治疗方案对湿热内蕴型肝豆状核变性（WD）患者肝脏代谢和认知功能的影响。方法：按照随机数字表法将2018年1月至2021年12月期间我院收治的80例WD患者分为观察组（n=40,接受肝豆汤联合驱铜治疗）、对照组（n=40,接受驱铜治疗）。观察两组中医证候积分、24 h尿铜、肝功能指标、肝纤维化指标和认知功能变化情况。结果：治疗4个疗程后,两组手足震颤、言语含糊、行动困难、步履艰难、肢僵挛缩、口涎不止、口苦或臭、头目昏眩、纳谷不香、腹胀痞满、尿赤便结、鼻衄齿衄、黄疸水臌评分均降低,且观察组均低于对照组（P<0.05）。治疗4个疗程后,两组24 h尿铜升高,且观察组高于对照组（P<0.05）。治疗4个疗程后,两组丙氨酸氨基转移酶（ALT）、天门冬氨酸转氨酶（AST）、总胆红素（TBIL）均下降,且观察组均低于对照组（P<0.05）。治疗4个疗程后,两组透明质酸（HA）、Ⅲ型前胶原肽（PⅢP）、层黏连蛋白（LN）、Ⅳ型胶原（CⅣ）均下降,且观察组均低于对照组（P<0.05）。治疗4个疗程后,两组视空间与执行功能、命名、注意力、语言、抽象能力、延迟回忆、定向力评分均升高,且观察组均高于对照组（P<0.05）。结论：肝豆汤联合驱铜治疗方案治疗湿热内蕴型WD患者,可有效缓解临床症状,调节肝脏代谢,改善认知功能。     

阿尔茨海默病患者血清P-tau-181、8-OHdG、Lp-PLA2水平与认知功能的关系及其预测价值分析

摘要 目的：探讨阿尔茨海默病（AD）患者血清磷酸化Tau蛋白-181（P-tau-181）、8-羟基脱氧鸟苷酸（8-OHdG）、脂蛋白相关磷脂酶A2（Lp-PLA2）水平与认知功能的关系及其预测价值。方法：选择2018年1月～2019年12月我院收治的AD患者90例作为AD组,血管源性痴呆（VD）患者90例作为VD组,同期于我院进行体检的健康者90例作为对照组,比较各组血清P-tau-181、8-OHdG、Lp-PLA2水平、蒙特利尔认知评估量表（MoCA）、简易智力状态检查量表（MMSE）、临床痴呆评定量表（CDR）评分,比较不同认知功能障碍程度AD患者血清P-tau-181、8-OHdG、Lp-PLA2水平,并分析各指标的相关性,应用ROC曲线分析血清P-tau-181、8-OHdG、Lp-PLA2水平对AD的预测价值。结果：AD组血清P-tau-181、8-OHdG、Lp-PLA2水平显著高于VD组和对照组（P＜0.05）,VD组和对照组血清P-tau-181、8-OHdG、Lp-PLA2水平比较无统计学差异（P>0.05）。AD组、VD组MoCA、MMSE评分显著低于对照组,CDR评分显著高于对照组（P＜0.05）,AD组和VD组MoCA、MMSE和CDR评分比较无统计学差异（P>0.05）。随着AD患者认知功能的降低,患者血清P-tau-181、8-OHdG、Lp-PLA2水平逐渐升高（P＜0.05）。Pearson相关性分析显示,AD患者血清P-tau-181、8-OHdG、Lp-PLA2与MoCA、MMSE评分呈负相关,与CDR评分呈正相关（P＜0.05）。ROC曲线分析显示,P-tau-181、8-OHdG、Lp-PLA2诊断AD的敏感度分别为88.55%、89.34%、89.77%,特异度分别为81.94%、82.56%、85.67%。结论：AD患者血清P-tau-181、8-OHdG、Lp-PLA2水平异常升高,其水平可以反映患者认知功能障碍程度,对AD的早期诊断和防治具有一定价值。     

Systemic vaccination with anti‐oligomeric monoclonal antibodies improves cognitive function by reducing Aβ deposition and tau pathology in 3xTg‐AD mice

Alzheimer's disease (AD) is a devastating disorder that is clinically characterized by a comprehensive cognitive decline. Accumulation of the amyloid‐beta (Aβ) peptide plays a pivotal role in the pathogenesis of AD. In AD, the conversion of Aβ from a physiological soluble monomeric form into insoluble fibrillar conformation is an important event. The most toxic form of Aβ is oligomers, which is the intermediate step during the conversion of monomeric form to fibrillar form. There are at least two types of oligomers: oligomers that are immunologically related to fibrils and those that are not. In transgenic AD animal models, both active and passive anti‐Aβ immunotherapies improve cognitive function and clear the parenchymal accumulation of amyloid plaques in the brain. In this report we studied effect of immunotherapy of two sequence‐independent non‐fibrillar oligomer specific monoclonal antibodies on the cognitive function, amyloid load and tau pathology in 3xTg‐AD mice. Anti‐oligomeric monoclonal antibodies significantly reduce the amyloid load and improve the cognition. The clearance of amyloid load was significantly correlated with reduced tau hyperphosphorylation and improvement in cognition. These results demonstrate that systemic immunotherapy using oligomer‐specific monoclonal antibodies effectively attenuates behavioral and pathological impairments in 3xTg‐AD mice. These findings demonstrate the potential of using oligomer specific monoclonal antibodies as a therapeutic approach to prevent and treat Alzheimer's disease.     

Bovine CLEC7A genetic variants and their association with seropositivity in Johne's disease ELISA

Mycobacterium avium ssp. paratuberculosis (MAP) infection in cattle causes significant economic losses to the dairy and beef industries resulting from reduced productivity, premature culling and mortality. Bovine Dectin-1, an important pattern recognition molecule that is able to generate a proinflammatory response by acting alongside Toll like receptor (TLR) signaling, is known to co-operate with TLR2 to specifically activate a macrophage proinflammatory response against mycobacterial infections. Therefore, the goal of this study was to identify single nucleotide polymorphisms (SNPs) in the gene encoding bovine Dectin-1 (CLEC7A) and to assess their association with susceptibility to MAP infection in dairy cattle. Blood and milk samples, collected from commercial dairy operations, were tested for MAP infection using blood and milk ELISAs and a resource population consisting of 197 infected and 242 healthy cattle was constructed. Pooled DNA was used for sequencing and eight single nucleotide polymorphisms (SNPs) were identified. Identified SNPs were genotyped on the resource population using the iPLEX MassARRAY system and statistical analysis was performed using logistic regression fitting the additive and dominance effects of each SNP in the model. Out of a total of eight identified SNPs, five were successfully genotyped, and three out of these five SNPs were found to be in complete linkage. Statistical analysis revealed a strong association between a non-synonymous SNP c.589A>G (p = 0.008), and MAP infection status of the resource population inferred by seropositivity in MAP antibody specific ELISAs. This SNP c.589A>G was located in the geneic region that encodes the carbohydrate recognition domain of bovine Dectin-1. Therefore, further investigation of its functional relevance is warranted.