Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Exploration of the association between serum uric acid and testosterone in adult males: NHANES 2011–2016

BackgroundPrevious studies have suggested that the possible relationship between serum uric acid (SUA) and testosterone. However, the results of previous studies are controversial and there is limited evidence examining the relationship between SUA and testosterone in a general US population of men. The objective of this study is to explore the correlation of SUA and testosterone among adult males from the US.MethodsData from the National Health and Nutrition Examination Survey 2011–2016 were used, including a total of 7,796 male participants aged 18 years or older and excluding those lacking serum testosterone and uric acid data. Clinical characteristics of the participants among different SUA groups and testosterone groups are compared. Univariate and multivariate linear regression analyses were applied to evaluate the association between SUA and testosterone.ResultsWe found an inverse association between SUA and testosterone after fully adjusted the potential confounding factors in general US adult males. In the multivariate linear regression analysis, we found that increasing age (estimate testosterone percent difference: −0.20% per year, P<0.01), uric acid (estimate testosterone percent difference: −4.40% per md/dL, P<0.01) and BMI (estimate testosterone percent difference: −2.86% per kg/m2, P<0.01) were associated with declining serum testosterone. This association remained significant in sensitivity analysis, while in the stratified analysis, above association was not significant in men with diabetes or aged 65 and over.ConclusionsSUA levels might be negatively associated with serum testosterone in adult males.     

The effect of culture on the sex differences in schizophrenia

Cultural influences on sex differences in clinical characteristics and symptomatology of schizophrenia were studied among 369 schizophrenic patients from the United States and Turkey. Male schizophrenics were more likely to be single, and were younger than female schizophrenics at onset of symptoms and when first diagnosed, treated and hospitalised in both cultures. Turkish male and female schizophrenics were more ambivalent, inappropriate, "silly", euphoric, depersonalised, dissociated, mute, conceptually disorganised, and exhibiting more flight of ideas and thought than American male and female schizophrenics. Irrelevant thought and stereotypic behaviour were most severe in Turkish male and American female schizophrenics. Hallucinatory behaviour was most intense in Turkish separated, divorced, or widowed female schizophrenics and American married male schizophrenics. Turkish married female and Turkish separated, divorced, or widowed male schizophrenics were most disoriented. Turkish single female schizophrenics were most mute. Turkish separated, divorced, or widowed male schizophrenics showed most intense stupor behaviour.     

亚甲基四氢叶酸还原酶基因多态性与脑血管疾病的研究

目的　探讨N 亚甲基四氢叶酸还原酶 (MTHFR)基因多态性与脑血管疾病的关系。方法　利用聚合酶链反应和限制性片段长度多态性 (PCR RFLP)方法 ,检测了 72名健康人和 71名脑血管疾病患者MTHFR基因的6 77碱基多态性突变C→T情况 ,并加以对照分析。结果　脑血管疾病患者MTHFR基因突变型V6 77基因的频率 ,与正常健康人对比差异无显著意义 (P >0 .0 5 )。结论　MTHFR基因突变型V6 77基因可能是脑血管疾病的又一个遗传风险因子 ,但本研究结果显示与脑血管疾病的发病无关 ,是否为脑血管病的遗传风险因素有待进一步研究。     

鼻咽癌患者前列环素及血栓素与外周血细胞免疫状况

应用间接免疫荧光法和放射免疫法分别检测了 34例鼻咽癌患者外周血中淋巴细胞的数量和血浆前列环素(PGI2 )及血栓素 (TXA2 )的含量 ,并与正常对照组对比研究。结果显示 :鼻咽癌患者外周血中 CD4细胞减少 (P<0 .0 1) ,而 CD8细胞则明显升高 (P<0 .0 5 )。同时鼻咽癌患者血浆中 PGI2 和 TXA2 的稳定代谢产物 6 - keto- PGF1α及 TXB2分别比对照组升高 ,以 TXB2 升高更明显 (P<0 .0 5 )。提示鼻咽癌患者体内前列腺素类物质 PGI2 和 TXA2 与鼻咽癌患者机体细胞免疫功能有关 ,并对其作为一种可能性抑制因素在鼻咽癌细胞免疫中的作用进行了讨论     

哑铃形椎管肿瘤29例临床分析

回顾性分析我院从 1 990年 3月～ 1 998年 1 1月 2 9例哑铃形椎管肿瘤的诊治。所有病例经CT ,MRI确诊。MRI能提供多时向、多空间图像 ,故可视为诊断哑铃形椎管肿瘤最有价值的方法。除 2例拒绝手术治疗外 ,2 7例采用后正中或后外侧入路作Ⅰ期显微手术切除 ,疗效较满意。本文重点讨论了该肿瘤的临床表现特征 ,CT ,MRI检查和手术治疗的特点     

脑梗死患者急性期血小板膜糖蛋白表达的研究

目的　探讨脑硬死患者急性期血小板膜P -选择素 (CD6 2p)的表达及其与临床神经功能缺损程度的关系。方法　用流式细胞术测定 41例急性期脑梗死患者血小板膜CD6 2 p的表达。 结果　轻、中、重型脑梗死患者CD6 2 p的表达分别为 (1.38± 0 .2 9) %、(3.15± 1.5 8) %、(10 .46± 5 .0 7) % ,与正常对照组 (1.5 6± 0 .17) %比 ,轻型脑梗死患者CD6 2p的表达无显著性差异 (P >0 .0 5 ) ,中、重型脑梗死患者CD6 2 p的表达显著升高 (P <0 .0 5和0 .0 1)。结论　脑梗死患者急性期血小板膜CD6 2 p的表达与临床神经功能缺损程度有关。     

非小细胞肺癌放疗期间外周血细胞数的变化

目的　研究胸部受电离辐射后外周血细胞的变化特点。方法　选取１９９７ ～１９９８ 年非小细胞肺癌患者３０ 例。按１∶２ 配比年龄相似,性别相同的非放疗慢性病患者作为对照组。观察胸部外照射对外周血白细胞、淋巴细胞、血小板数的影响。ＮＳＣＬＣ以医用直线加速器６ ＭＶ－ Ｘ 线,常规分割放射治疗。射野包括肿瘤及其周围１ ～２ｃｍ 正常肺组织,同侧肺门以及纵膈,有时包括锁骨上区ＦＳＺ（Ｆｉｅｌｄｓｑｕａｒｅｚｏｏｍ） ７２ ～２４６ｃｍ２ ,剂量率２Ｇｙ／ｍｉｎ ,ＳＳＤ１００ｃｍ 。采用ＳＷＧＥＡＢＡＣ－ ９２０ 型血液细胞自动分析仪检测外周血白细胞、淋巴细胞、血小板数,并严格质量控制。结果　当吸收剂量１０Ｇｙ／５ｆ／ Ｗ ,ＮＳＣＬＣ外周血细胞数量开始下降;至２０ ～３０Ｇｙ／１０ ～１５ｆ／２ ～３ Ｗ 时,其外周血细胞数量降至低谷。并且上述３ 种细胞数量较之放疗前和对照组具有显著差异（ｔ＞ ２．５８ ,Ｐ＜ ０．０１）。另外,局部照射野＞ １００ｃｍ２ 组外周血白细胞数显著低于照射野为＜ １００ｃｍ２ 组,（ Ｆ＝６ ．４６,Ｐ＜ ０ ．０１）。在缩野和改侧斜野,放疗第四周（Ｄｔ＝ ４０Ｇｙ） 后,局部受损骨髓开始修复,受照区内的毒性产物被迅速稀