填埋场封场土地沉降特性分析与模拟研究

通过对上海老港填埋场49号填埋单元进行的地面沉降监测,分析堆体沉降机理,建立了反映填埋场沉降特性的数学模型,结果表明:垃圾堆体在监测期内平均表面沉降量77.62 mm,沉降速率约为0.174 mm/d,模型预测监测堆体最终沉降量约为122 cm,未来5 a内还将有约7.9 cm沉降。     

Speech Perception with Noise Vocoding and Background Noise: An EEG and Behavioral Study

This study explored the physiological response of the human brain to degraded speech syllables. The degradation was introduced using noise vocoding and/or background noise. The goal was to identify physiological features of auditory-evoked potentials (AEPs) that may explain speech intelligibility. Ten human subjects with normal hearing participated in syllable-detection tasks, while their AEPs were recorded with 32-channel electroencephalography. Subjects were presented with six syllables in the form of consonant-vowel-consonant or vowel-consonant-vowel. Noise vocoding with 22 or 4 frequency channels was applied to the syllables. When examining the peak heights in the AEPs (P1, N1, and P2), vocoding alone showed no consistent effect. P1 was not consistently reduced by background noise, N1 was sometimes reduced by noise, and P2 was almost always highly reduced. Two other physiological metrics were examined: (1) classification accuracy of the syllables based on AEPs, which indicated whether AEPs were distinguishable for different syllables, and (2) cross-condition correlation of AEPs (r_cc) between the clean and degraded speech, which indicated the brain’s ability to extract speech-related features and suppress response to noise. Both metrics decreased with degraded speech quality. We further tested if the two metrics can explain cross-subject variations in their behavioral performance. A significant correlation existed for r_cc, as well as classification based on early AEPs, in the fronto-central areas. Because r_cc indicates similarities between clean and degraded speech, our finding suggests that high speech intelligibility may be a result of the brain’s ability to ignore noise in the sound carrier and/or background.     

Genes in the serotonin pathway are associated with bipolar affective disorder in a Han Chinese population

Serotonin plays an important role in mood regulation, but the involvement of serotonin pathway genes in the development of bipolar I disorder (BP-I), a mood disorder, is not clear. We selected 21 singlenucleotide polymorphisms (SNPs) within the HTR2A gene, 8 within the SLC6A4 gene and 23 within the TPH2 gene for genotyping using the GoldenGate genotyping assay. A total of 375 patients with BP-I and 475 normal controls were recruited. Two out of 21 SNPs (rs1475196 and rs9567747) in the HTR2A gene and 1/23 SNPs (rs17110566) in the TPH2 gene were significantly associated with BP-I, both genotype-wise and allele-wise. Furthermore, a specific haplotype in the HTR2A gene showed a significant association with BP-I. Our results indicate that the HTR2A and TPH2 genes in the serotonin pathway play important roles in susceptibility to BP-I.     

大面积烧伤患儿静脉导管感染病原菌情况调查与耐药性分析

 目的 探讨大面积烧伤患儿静脉导管感染病原菌情况,分析其耐药性。方法 选取2014-01至2019-01武警辽宁总队医院和解放军总医院第三医学中心烧伤科收治的478例烧伤患儿,收集所有患儿的静脉导管进行细菌培养与鉴定,对按不同因素分类的置管后患儿中心静脉导管感染情况进行对比分析。结果 478例静脉导管中共分离出病原菌304株。其中革兰阳性菌113株(37.17%),革兰阴性菌183株(60.20%),真菌8株(2.63%)。药敏试验显示:金黄色葡萄球菌对万古霉素和利奈唑胺敏感;铜绿假单胞菌对哌拉西林/他唑巴坦和亚胺培南敏感。男女感染率对比差异无统计学意义,不同年龄患儿感染率对比,差异有统计学意义(P<0.05);中心静脉导管穿刺部位股、颈内、锁骨下静脉感染率、导管留置及住院时间不同感染率对比,差异均有统计学意义(P<0.05)。结论 大面积烧伤患儿年龄越小感染率越高,股静脉感染率较重,留置、住院时间越长感染率越高。     

MiR-132 Inhibits Expression of SIRT1 and Induces Pro-inflammatory Processes of Vascular Endothelial Inflammation through Blockade of the SREBP-1c Metabolic Pathway

Purpose

Inflammation participates centrally in all stages of atherosclerosis (AS), which begins with pro-inflammatory processes and inflammatory changes in the endothelium, related to lipid metabolism. MicroRNA (miRNA) inhibition of inflammation related to SIRT1 has been shown to be a promising therapeutic approach for AS. However, the mechanism of action is unknown.

Methods

We investigated whether miRNAs regulate the SIRT1 and its downstream SREBP-lipogenesis-cholesterogenesis metabolic pathway in human umbilical vein endothelial cells (HUVECs). HUVECs were transfected with miR-132 mimics and inhibitors, and then treated with or without tumor necrosis factor α (TNFα). The effects of miR-132 on pro-inflammatory processes, proliferation and apoptosis were assessed.

Results

We identified that the relative 3’ UTR luciferase activities of SIRT1 were significantly decreased in miR-132 transfected HUVECs (0.338?±?0.036) compared to control (P?=?0.000). miR-132 inhibited SIRT1 expression of mRNA level in HUVECs (0.53?±?0.06) (P?SIRT1. mRNA expression and protein levels of SREBP (0.45?±?0.07), fatty acid synthase (FASN) (0.55?±?0.09) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) (0.62?±?0.08) (P?TNF-α, and inhibited its proliferation, viability and migration.

Conclusions

SIRT1 mRNAs are direct targets of miR-132. miR-132 controls lipogenesis and cholesterogenesis in HUVECs by inhibiting SIRT1 and SREBP-1c expression and their downstream regulated genes, including FASN and HMGCR. Inhibition of SIRT1 by miR-132 was associated with lipid metabolism-dependent pro-inflammatory processes in HUVECs. The newly identified miRNA, miR-132 represents a novel targeting mechanism for AS therapy.     

一体化PET/MR结合统计参数图辅助^11C-PIB显像的半定量分析及其临床应用

目的 研究一体化PET/MR结合统计参数图(SPM)辅助^11C-匹兹堡化合物B(PIB)用于β-淀粉样蛋白(Aβ)PET显像半定量分析的准确性,探索其用于认知障碍的诊断及鉴别诊断的可行性.方法 回顾分析2018年1月至2019年9月在华中科技大学同济医学院附属协和医院PET中心进行^11C-PIB PET/MR扫描,临床最终确诊的13例阿尔茨海默病(AD)患者[男4例,女9例;年龄(59.2±5.8)岁]和10例血管性认知障碍(VCD)患者[男9例,女1例;年龄(59.5±11.5)岁].结合三维T1加权成像(3D T1WI)对^11C-PIB PET图像分别进行脑区手动勾画和SPM辅助半自动分割,获得8个关键脑区(大脑白质、纹状体、丘脑、后扣带回、额叶皮质、后顶叶皮质、颞叶外侧皮质和枕叶皮质)与小脑皮质的标准摄取值比值(SUVR).对2种方法所获结果进行Pearson相关分析;采用两独立样本t检验、配对t检验分析数据.结果 AD组与VCD组患者的年龄和简易精神状态检查量表(MMSE)评分[(19.7±4.7)和(21.7±3.8)分]差异均无统计学意义(t值:0.095和1.098,均P>0.05).除丘脑外(r=0.179,P=0.413),分割法和勾画法在其余7个关键脑区获得的SUVR均有良好的相关性(r值:0.678~0.893,均P<0.05).AD组8个关键脑区的SUVR均明显高于VCD组(1.519~2.055与1.105~1.618;t值:2.799~11.582,均P相似文献   

Evidence that the LRRK2 ROC domain Parkinson's disease‐associated mutants A1442P and R1441C exhibit increased intracellular degradation

Mutations in the leucine‐rich repeat kinase 2 (lrrk2) gene are the leading genetic cause of Parkinson's disease (PD). In characterizing the novel ROC domain mutant A1442P, we compared its steady‐state protein levels, propensity to aggregate, and toxicity with the pathogenic R1441C mutant and wild‐type (WT) LRRK2. Mutant (R1441C and A1442P) and WT LRRK2 fused to green fluorescent protein (GFP) and FLAG were transiently expressed in HEK293 cells using plasmid constructs. Western analysis and fluorescence microscopy consistently demonstrated lower mutant LRRK2 protein levels compared with WT. A time‐course expression study using flow cytometry showed that WT LRRK2 expression increased initially but then plateaued by 72 hr. Conversely, R1441C and A1442P mutant expression attained 85% and 74% of WT levels at 24 hr but fell to 68% and 55% of WT levels by 72 hr, respectively. We found that proteasome inhibition markedly increased mutant LRRK2 to levels approaching those of WT. Taken together, our findings reveal increased intracellular degradation for both mutants. Furthermore, the impact of mutant and WT LRRK2 expression on HEK293 cell viability was assessed under normative and oxidative (hydrogen peroxide) conditions and found not to differ. Expression of WT and mutant LRRK2 protein gave rise to intracellular aggregates of similar appearance and cellular localization. In summary, we provide evidence that the novel A1442P mutant and the previously investigated R1441C pathogenic mutant exhibit increased intracellular degradation, a property reportedly demonstrated for the pathogenic LRRK2 kinase domain mutant I2020T. © 2013 Wiley Periodicals, Inc.     

一例3-甲基戊烯二酸尿症Ⅶ型患儿的临床和遗传学分析

目的对一例全面发育落后的婴儿进行临床和遗传学分析,明确其病因。方法采集患儿及其家系成员的病史,应用实验室检查、遗传代谢病筛查和新一代测序技术对该家系进行临床和遗传学分析。结果先证者临床表现为对声音反应不灵敏,竖头不稳,不能翻身、逗笑,不认识母亲。实验室检查血乳酸、血糖等正常,尿有机酸中3-甲基戊烯二酸、3-甲基戊二酸水平增高,提示为"3-甲基戊烯二酸尿症可能"。头颅磁共振扫描显示胼胝体压部T1W信号偏低,髓鞘化落后于月龄。高通量测序发现CLPB基因存在复合杂合变异c.1085G>A和c.1700A>C,分别遗传自父亲和母亲,二者均为新变异。根据美国医学遗传学与基因组学学会标准,两个变异均预测为疑似致病变异。结论该患儿可能为CLPB基因变异引起的3-甲基戊烯二酸尿症Ⅶ型。高通量测序技术为分析该类疾病提供了有力的诊断工具。