CD8+T-bet+ cells as a predominant biomarker for inclusion body myositis

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months

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卵巢癌肿瘤标志物研究进展

卵巢癌是妇科三大恶性肿瘤之一,由于疾病早期没有明显的临床症状,发现时多已进展为晚期,且约80%的晚期患者在治疗后3年内复发,因此卵巢癌成为妇科恶性肿瘤中死亡率最高的肿瘤。早期有效的筛查及预后评估机制对卵巢癌的诊断及治疗有重要意义。CA125是监测卵巢癌病程和转归的重要标志物,然而其特异性不足,其他标志物包括HE4、CA199对卵巢癌的诊断和预后也缺乏敏感性和特异性。因此,寻找和鉴定新的分子标志物用于早期筛查和诊断卵巢癌以及评估预后至关重要。本文基于目前卵巢癌生物标志物最新研究进行综述。     

A Systematic Review of the Evidence for the Decipher Genomic Classifier in Prostate Cancer

ContextMolecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions remain as to whether sufficient evidence supports adoption of these biomarkers for clinical use.ObjectiveTo perform a systematic review of the available evidence supporting the clinical utility of the Decipher genomic classifier (GC).Evidence acquisitionThe review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching PubMed and conference abstracts from January 2010 to June 2020. Evidence was then graded using the criteria of Simon et al (Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009;101:1446–52) and American Urology Association (AUA) criteria.Evidence synthesisIn total, 42 studies and 30 407 patients were included. GC performance data were available for localized, postprostatectomy, nonmetastatic castration-resistant, and metastatic hormone-sensitive PCa as part of retrospective studies (n = 12 141), prospective registries (n = 17 053), and prospective and post hoc randomized trial analyses (n = 1213). In 32 studies (n = 12 600), the GC was independently prognostic for all study endpoints (adverse pathology, biochemical failure, metastasis, and cancer-specific and overall survival) on multivariable analysis and improved the discrimination over standard of care in 24 studies (n = 8543). GC use changed the management in active surveillance (number needed to test [NNT] = 9) and postprostatectomy (NNT = 1.5–4) settings in five studies (n = 4331). Evidence strength was levels 1 and 2 by the Simon criteria for all disease states other than high-risk PCa, and grades A and B by AUA criteria depending on disease state.ConclusionsConsistent data are now present from diverse levels of evidence, which when viewed together, have demonstrated clinical utility of the GC in PCa. The utility of the GC is strongest for intermediate-risk PCa and postprostatectomy decision-making.Patient summaryIn this paper, we review the evidence of the Decipher genomic classification tool for men with prostate cancer. We found consistent evidence that the test helps identify which cancers are more or less aggressive, which in turn aids in personalized treatment decision-making.     

Blood biomarkers of mild traumatic brain injury: State of art

BackgroundMild traumatic brain injury (mTBI) is one of the most common causes of emergency department visits around the world. Up to 90% of injuries are classified as mTBI. Cranial computed tomography (CCT) is a standard diagnosis tool to identify intracranial complications in adults with mTBI. Alternatively, children can be admitted for inpatient observation with CCT scans performed only on those with clinical deterioration. The use of blood biomarkers is a supplementary tool for identifying patients at risk of intracerebral lesions who may need imaging.MethodWe realised a bibliographic state of art providing a contemporary clinical and laboratory framework for blood biomarker testing in mTBI management.ResultsThe S100B protein is the only biomarker that can be used today in the clinical routine for management of mTBI with appropriate evidence-based medicine. Due to its excellent negative predictive value, S100B protein is an alternative choice to CCT scanning for mTBI management with considered, consensual and pragmatic use. In this state of art, we propose points to help clinicians and clinical pathologists use serum S100B protein in the clinical routine. A state of art on the different biomarkers (GFAP, UCH-L1, NF [H or L], tau, H-FABP, SNTF, NSE, miRNAs, MBP) is also conducted. Some of these other biomarkers, used alone (GFAP, UCH-L1) or in combination (GFAP + H-FABP ± S100B ± IL10) can improve the specificity of S100B.ConclusionUsing a bibliographic state of art, we highlighted the added values of the blood biomarkers for the clinical management of mTBI.     

基于代谢组学技术的黄芩-白芍对2型糖尿病模型小鼠的作用机制

目的：在肾脏代谢组学技术基础上,探讨黄芩-白芍药对对2型糖尿病（T2DM）的防治机制,并通过寻找内源性潜在生物标志物,寻找其相关代谢通路。方法：非糖尿病健康同窝出生仔畜(db/m小鼠）为空白组,同时选择血糖值高于11.1 mol/L的糖尿病瘦素受体基因缺陷（db/db）小鼠进行分组,分为模型组、黄芩-白芍组（5.625 g/kg）、阳性药组（二甲双胍250 mg/kg）,给药体积为7.5 mL/kg,1次/d,连续8周,并采用超高效液相色谱与串联四级杆飞行时间质谱仪联用技术(UPLC-Q-TOF-MS/MS)法进行小鼠肾脏代谢组学分析,探寻潜在的生物标志物,联合人类代谢组学数据库（HMDB）和京都基因与基因组百科全书数据库（KEGG）找出相关代谢通路。结果：黄芩-白芍组可改善T2DM模型小鼠代谢轨迹的偏离,同时,寻找出与DN模型及给予黄芩汤干预后具有共同差异的生物标志物14个,涉及8条相关代谢通路,应用相关代谢通路分析方法发现,影响最为广泛的代谢通路可能是甘油磷脂代谢、嘌呤代谢和嘧啶代谢。结论：黄芩-白芍药对治疗T2DM的作用机制可能与其通过调节脂质代谢、能量代谢等多条代谢通路,改善内源性代谢物的水平,恢复机体正常代谢活动有关。     

肝癌免疫治疗策略的进展与思考

中国是肝癌大国,全世界每年>50%的新发和死亡病例发生在中国。肝癌的化疗敏感性较低,以抗血管生成为主的靶向治疗是进展期肝癌的主要系统治疗手段,但能达到的有效率和生存延长作用十分有限。近年来,免疫检查点抑制剂在肝癌临床治疗中展现出较好疗效,正在改变肝癌治疗格局,但也面临诸多问题。如程序性死亡配体-1、肿瘤突变负荷、错配修复蛋白等临床常用生物标志物在肝癌的临床应用价值十分有限。与其他病因相关肝癌比较,中国乙型病毒性肝炎相关肝癌具有其独特的基因变异图谱,但基于分子分型的个体化治疗策略尚未建立。更加有效且多样化的系统治疗手段,可推动肝癌进入综合治疗新时代,相关诊断与治疗规范有待进一步探索和确立。笔者查阅相关文献,结合临床实践,探讨肝癌免疫治疗策略的进展与思考。     

Investigations into the effects of various hepatotoxic compounds on urinary and liver taurine levels in rats

The effect of various hepatotoxicants on urinary taurine and urinary creatine has been studied in the rat. Several hepatotoxic agents, carbon tetrachloride, thioacetamide, galactosamine and allyl alcohol which all caused hepatic necrosis (sometimes accompanied by steatosis), resulted in a rise in urinary taurine and in some cases creatine, when administered to rats. Ethionine and hydrazine also raised urinary taurine but caused only steatosis and did not raise urinary creatine. Therefore urinary taurine and possibly creatine may be useful markers of liver injury and dysfunction. Liver taurine levels were also affected by some of the hepatotoxicants but in those cases where there was a rise in urinary taurine this could not be accounted for by the loss in liver taurine. It is suggested that the increase in urinary taurine is partly due to changes in protein synthesis and hence in sulphur amino acid metabolism caused by hepatotoxic agents. However, bromobenzene did not increase urinary taurine and-naphthylisothiocyanate and lithocholate caused reduced levels. It is suggested that this lack of increase in urinary taurine may be due to depletion of glutathione or interference with the biliary system.     

Clinical Validation of a New Immunoradiometric Assay for Intact Human Osteocalcin

The purpose of this study was to estimate clinical validity of a new available immunoradiometric assay for circulating intact human BGP (N-tact Osteo SP) by measuring this protein in a large number of normal subjects and patients with the most common metabolic bone diseases. One hundred normal subjects were studied in order to obtain our normal ranges (4.9 ± 1.7 ng/ml). The mean values found in 28 patients with primary hyperparathyroidism (17.5 ± 22.8 ng/ml, P < 0.001), 15 glucocorticoid-treated patients (1.9 ± 1.5, P < 0.001), 10 patients with hypoparathyroidism (1.5 ± 0.7, P < 0.001), 9 with hyperthyroidism (8.3 ± 3.8, P < 0.001), 8 with skeletal metastases (7.2 ± 2.3, P < 0.001), and 4 with humoral hypercalcemia of malignancy (2.42 ± 1.91, P < 0.005) were significantly different from mean values found in normal subjects. Mean decrease of serum osteocalcin T-score values was significantly greater when evaluated by N-tact Osteo SP assay in 15 steroid-treated patients (−1.4 ± 1.0) and 19 primary hyperparathyroid (PHPT) patients (3.6 ± 1.9), compared with the mean values obtained with the Elsa-Osteo assay (−0.67 ± 1.2, P < 0.002 and 4.3 ± 2.8, P < 0.04, respectively). We found significant correlations between the global skeletal uptake of 99mTc-methylendiphosphonate and serum BGP levels assayed by both N-tact Osteo SP (P < 0.01) and Elsa-Ost-Nat assay (P < 0.05). Our results indicate that this new immunoradiometric assay for the intact human osteocalcin has the potential for good discrimination between normal subjects and patients with both low and high bone turnover. Furthermore, our findings emphasize the fact that, in the absence of available standardized commercial assays, one should rely on only one assay because different results are obtained by different assays under different clinical conditions. Received: 22 January / Accepted: 22 September 1998