Tau as a biomarker of cognitive impairment and neuropsychiatric symptom in Alzheimer's disease

The A/T/N research framework has been proposed for the diagnosis and prognosis of Alzheimer''s disease (AD). However, the spatial distribution of ATN biomarkers and their relationship with cognitive impairment and neuropsychiatric symptoms (NPS) need further clarification in patients with AD. We scanned 83 AD patients and 38 cognitively normal controls who independently completed the mini‐mental state examination and Neuropsychiatric Inventory scales. Tau, Aβ, and hypometabolism spatial patterns were characterized using Statistical Parametric Mapping together with [18F]flortaucipir, [18F]florbetapir, and [18F]FDG positron emission tomography. Piecewise linear regression, two‐sample t‐tests, and support vector machine algorithms were used to explore the relationship between tau, Aβ, and hypometabolism and cognition, NPS, and AD diagnosis. The results showed that regions with tau deposition are region‐specific and mainly occurred in inferior temporal lobes in AD, which extensively overlaps with the hypometabolic regions. While the deposition regions of Aβ were unique and the regions affected by hypometabolism were widely distributed. Unlike Aβ, tau and hypometabolism build up monotonically with increasing cognitive impairment in the late stages of AD. In addition, NPS in AD were associated with tau deposition closely, followed by hypometabolism, but not with Aβ. Finally, hypometabolism and tau had higher accuracy in differentiating the AD patients from controls (accuracy = 0.88, accuracy = 0.85) than Aβ (accuracy = 0.81), and the combined three were the highest (accuracy = 0.95). These findings suggest tau pathology is superior over Aβ and glucose metabolism to identify cognitive impairment and NPS. Its results support tau accumulation can be used as a biomarker of clinical impairment in AD.     

Hippocampus‐prefrontal cortex inputs modulate spatial learning and memory in a mouse model of sepsis induced by cecal ligation puncture

AimsSepsis‐associated encephalopathy (SAE) often leads to cognitive impairments. However, the pathophysiology of SAE is complex and unclear. Here, we investigated the role of hippocampus (HPC)‐prefrontal cortex (PFC) in cognitive dysfunction in sepsis induced by cecal ligation puncture (CLP) in mice.MethodsThe neural projections from the HPC to PFC were first identified via retrograde tracing and viral expression. Chemogenetic activation of the HPC‐PFC pathway was shown via immunofluorescent staining of c‐Fos‐positive neurons in PFC. Morris Water Maze (MWM) and Barnes maze (BM) were used to evaluate cognitive function. Western blotting analysis was used to determine the expression of glutamate receptors and related molecules in PFC and HPC.ResultsChemogenetic activation of the HPC‐PFC pathway enhanced cognitive dysfunction in CLP‐induced septic mice. Glutamate receptors mediated the effects of HPC‐PFC pathway activation in CLP mice. The activation of the HPC‐PFC pathway resulted in significantly increased levels of NMDAR, AMPAR, and downstream signaling molecules including CaMKIIa, pCREB, and BDNF in PFC. However, inhibition of glutamate receptors using 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo (F)quinoxaline (NBQX), which is an α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR inhibitor), or D‐2‐amino‐5‐phosphonopentanoate (D‐AP5), which is an NMDA receptor antagonist abolished this increase.ConclusionOur study reveals the important role of the HPC‐PFC pathway in improving cognitive dysfunction in a mouse model of CLP sepsis and provides a novel pathogenetic mechanism for SAE.     

Different Clinical Courses of Nephronophthisis in Dizygotic Twins

Siblings with nephronophthisis occasionally show different clinical courses; however, the reasons for this remain unclear. We herein report cases of nephronophthisis in a pair of dizygotic twins with different clinical courses. The brother developed end-stage kidney disease at 17 years old; however, his sister did not show kidney insufficiency. Kidney biopsies revealed severe tubulointerstitial damage at 14 and 22 years old in the brother and sister, respectively. Both had a homozygous NPHP1 deletion with different heterozygous mutations related to hereditary cystic kidney disease. Since the dizygotic twins were exposed to similar environmental factors, genetic factors may have influenced their clinical course more strongly than environmental factors.     

Emodin alleviates lung ischemia–reperfusion injury by suppressing gasdermin D‐mediated pyroptosis in rats

BackgroundPyroptosis refers to programmed cell death associated with inflammation. Emodin has been reported to alleviate lung injuries caused by various pathological processes and attenuate ischemia–reperfusion (I/R) injuries in diverse tissues.MethodsLewis rats were assigned into the sham, the I/R, and the I/R + emodin groups. Emodin and phosphate‐buffered saline were intraperitoneally injected into rats of the emodin group and I/R group for 30 min, respectively. These rats were then subjected to left thoracotomy followed by 90‐min clamping of the left hilum and 120‐min reperfusion. Sham‐operated rats underwent 210‐min ventilation. Lung functions, histological changes, lung edema, and cytokine levels were assessed. Protein levels were measured by western blotting. Immunofluorescence staining was conducted to evaluate pyroptosis.ResultsEmodin alleviated the I/R‐induced lung dysfunction, lung damages, and inflammation. Protective effects of emodin against I/R‐mediated endothelial pyroptosis was observed in vivo and in vitro. Mechanistically, emodin inactivated the TLR4/MyD88/NF‐κB/NLRP3 pathway.ConclusionEmodin attenuates lung ischemia–reperfusion injury by inhibiting GSDMD‐mediated pyroptosis in rats.     

Correction of Hypercortisolemia with an Improved Cognitive Function and Muscle Mass after Transsphenoidal Surgery in an Older Patient with Cushing's Disease

Cushing''s disease causes numerous metabolic disorders, cognitive decline, and sarcopenia, leading to deterioration of the general health in older individuals. Cushing''s disease can be treated with transsphenoidal surgery, but thus far, surgery has often been avoided in older patients. We herein report an older woman with Cushing''s disease whose cognitive impairment and sarcopenia improved after transsphenoidal surgery. Although cognitive impairment and sarcopenia in most older patients show resistance to treatment, our case indicates that normalization of the cortisol level by transsphenoidal surgery can be effective in improving the cognitive impairment and muscle mass loss caused by Cushing''s disease.     

蛋白A免疫吸附治疗肺移植术后新生DSA介导的急性排斥反应

目的  探讨肺移植术后新生供者特异性抗体(dnDSA)介导的急性排斥反应的治疗方法。方法  回顾性分析1例肺移植术后早期出现抗体介导的急性排斥反应(AMR)受者的资料,分析其诊疗经过。结果  受者因系统性硬化症相关性终末期间质性肺病接受右肺移植,术前群体反应性抗体(PRA)Ⅰ类阳性(11%),术前未行特殊预处理,手术当日及术后予以抗胸腺细胞球蛋白诱导治疗。术后早期受者康复顺利,术后13 d出现胸闷、气促,并呈进行性加重,迅速进展为Ⅰ型呼吸衰竭,PRA Ⅰ类上升为58%,并出现dnDSA,其位点为A24：02,平均荧光强度(MFI)值为2 110,据国际心肺移植学会指南,拟诊为(可能)AMR。予血浆置换、蛋白A免疫吸附、糖皮质激素冲击、利妥昔单抗及免疫球蛋白静脉滴注等综合治疗后,PRA及DSA水平逐渐下降,术后20 d DSA MFI值为0,受者临床情况逐渐好转,呼吸困难消失,气促逐渐缓解,呼吸衰竭纠正,肺部渗出影逐渐吸收;术后45 d,受者完全康复出院。随访1年,受者状态良好,生活质量与同龄健康人相同,PRA Ⅰ类为5%,Ⅱ类为阴性,未出现DSA。结论  在传统药物治疗基础上加用蛋白A免疫吸附治疗,能有效去除受者循环血液中的DSA,减轻靶器官损害,近期及远期治疗效果理想。针对肺移植术后AMR,采用传统药物治疗联合免疫吸附,可以达到理想治疗效果。     

体素内不相干运动扩散加权成像对原发性肝细胞肝癌患者经导管动脉栓塞化疗疗效的评估价值

目的 探讨体素内不相干运动扩散加权成像(IVIM-DWI)对原发性肝细胞肝癌(HCC)患者经导管动脉栓塞化疗(TACE)疗效的评估价值.方法 80例HCC患者均接受TACE治疗,术后根据实体瘤疗效评价标准分为稳定组(n=45)和进展组(n=35),所有患者TACE前后均接受IVIM-DWI检查,检测纯扩散系数(D)、伪...     

南宁市肺结核病发病率灰色系统模型及预测

对广西南宁市(含郊区)1996~2005年肺结核发病率建立灰色系统模型,并预测2008年和2010年发病率,使结核病的防治和控制更科学、更有效。     

广州居民新型冠状病毒肺炎知信行状况调查

目的了解广州市应急健康传播教育后,居民对新型冠状病毒肺炎(NCP)的知信行情况,为下一步开展新冠肺炎疫情宣传防控工作提供依据。方法 2020年2月,采用滚雪球抽样方法对195 282名居民新冠肺炎知信行情况进行问卷调查,使用SPSS 23.0对数据进行描述性分析。结果居民对新冠肺炎病相关知识的知晓率和个人防护行为执行率相对较高,分别为(70.73%～98.92%)和(88.87%～98.30%),差异均有统计学意义(χ²=143 783.668,P <0.001;χ²=22 679.015,P <0.050)。绝大部分居民愿意配合政府实施相关防控措施(98.90%～99.78%),差异有统计学意义(χ²=3 364.959,P <0.001)。结论居民对新冠肺炎相关基本知识知晓率和个人防护行为执行率相对较高,应对居民的知信行进行动态监测,为后续防控措施制定和实施提供参考。     

人力资本的理论研究及其新视角——关注家庭培训和小孩的人力资本投资

探讨西方现代人力资本理论,发现一个被忽略的重要领域——家庭培训。像“在职培训”一样,家庭培训是一种非正规教育,它需要大量的时间投入,并且是正规学校教育的一种补充。在家庭生产中,父母除了选择娱乐、工作,还要选择某种家庭活动方式。有工作的母亲常常通过减少休闲、睡眠和其他家庭活动时间来保证与小孩接触的时间,而在这些时间内,一些活动是能对小孩的人力资本的形成产生有益的作用。