Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species.     

食蟹猴静脉注射抗HER2人源化抗体急性毒性研究

目的 评价抗HER2 人源化抗体的急性毒性。方法 将食蟹猴随机分为4 组,包括溶媒对照和抗HER2 人源化抗体75、150 和250 mg/kg 组,单次iv 溶媒对照组或供试品,进行各项毒理学指标检测。结果 给药后各组动物临床症状、体质量、摄食量、体温、心电图、血压和血液学检测均未见明显异常;血清生化结果显示,150 mg/kg 组与250 mg/kg 组动物给药后血清IgG 水平出现一过性增加;各组动物均未见大体病理学改变。结论 食蟹猴单次iv 抗HER2 单抗,总体上动物具有良好的耐受性,最大耐受剂量可达250 mg/kg,这些结果为进一步临床前评价抗HER2 人源化单克隆抗体的安全性奠定了基础。     

Molecular Mechanisms of Lipoic Acid Protection against Aflatoxin B1-Induced Liver Oxidative Damage and Inflammatory Responses in Broilers

Alpha-lipoic acid (α-LA) was evaluated in this study for its molecular mechanisms against liver oxidative damage and inflammatory responses induced by aflatoxin B₁ (AFB₁). Birds were randomly allocated into four groups with different diets for three weeks: a basal diet, a 300 mg/kg α-LA supplementation in a basal diet, a diet containing 74 μg/kg AFB₁, and 300 mg/kg α-LA supplementation in a diet containing 74 μg/kg AFB₁. In the AFB₁ group, the expression of GSH-P_X mRNA was down-regulated (p < 0.05), and the levels of lipid peroxide and nitric oxide were increased (p < 0.05) in the chicken livers compared to those of the control group. Additionally, the mRNA level of the pro-inflammatory factor interleukin-6 was up-regulated significantly (p < 0.05), the protein expressions of both the nuclear factor kappa B (NF-κB) p65 and the inducible nitric oxide synthase were enhanced significantly (p < 0.05) in the AFB₁ group. All of these negative effects were inhibited by α-LA. These results indicate that α-LA may be effective in preventing hepatic oxidative stress, down-regulating the expression of hepatic pro-inflammatory cytokines, as well as inhibiting NF-κB expression.     

冷处理对单增李斯特菌生物膜形成能力的影响

目的研究冷处理对不同食品来源及不同血清型的单增李斯特菌生物膜形成能力的影响,为食品中单增李斯特菌的防治提供基础信息。方法使用结晶紫染色法对单增李斯特菌食品分离株在37 ℃、4 ℃冷胁迫及4 ℃冷适应条件下生物膜形成能力进行测定,并对代表菌株的生物膜相关基因hpt、luxS及sigB进行基因序列分析及表达量差异分析。结果37 ℃条件下,1/2c血清型单增李斯特菌生物膜形成能力较强,不存在生物膜形成能力弱株。 37 ℃条件下的生物膜形成能力强组（3株）以及中组（10株）菌株中,9株菌的hpt基因发生非同义突变。 冷处理条件下4株中组菌株中,1株菌的sigB基因表达量增多,3株菌的hpt基因表达量增多。结论单增李斯特菌生物膜形成能力与血清型相关,1/2c血清型菌株在37 ℃条件下具有较强生物膜形成能力。 hpt基因突变株在37 ℃下具有较强生物膜形成能力,冷处理使得病原菌生物膜形成能力降低,但hpt及sigB基因的过量表达会增强4 ℃条件下单增李斯特菌生物膜形成能力。     

Genomic and comparative genomic analyses of Rickettsia heilongjiangensis provide insight into its evolution and pathogenesis

Rickettsia heilongjiangensis, the causative agent of far eastern spotted fever, is an obligate intracellular gram-negative bacterium that belongs to the spotted fever group rickettsiae. To understand the evolution and pathogenesis of R. heilongjiangensis, we analyzed its genome and compared it with other rickettsial genomes available in GenBank. The R. heilongjiangensis chromosome contains 1333 genes, including 1297 protein coding genes and 36 RNA coding genes. The genome also contains 121 pseudogenes, 54 insertion sequences, and 39 tandem repeats. Sixteen genes encoding the major components of the type IV secretion systems were identified in the R. heilongjiangensis genome. In total, 37 β-barrel outer membrane proteins were predicted in the genome, eight of which have been previously confirmed to be outer membrane proteins. In addition, 266 potential virulence factor genes, seven partially deleted antibiotic resistance genes, and a genomic island were identified in the genome. The codon usage in the genome is compatible with its low GC content, and the amino acid usage shows apparent bias. A comparative genomic analysis showed that R. heilongjiangensis and R. japonica share one unique fragment that may be a target sequence for a diagnostic assay. The orthologs of 37 genes of R. heilongjiangensis were found in pathogenic R. rickettsii str. Sheila Smith but not in non-pathogenic R. rickettsii str. Iowa, which may explain why R. heilongjiangensis is pathogenic. Pan-genome analysis showed that R. heilongjiangensis and 42 other rickettsiae strains share 693 core genes with a pan-genome size of 4837 genes. The pan-genome-based phylogeny showed that R. heilongjiangensis was closely related to R. japonica.     

养老机构老年人移动体征监测系统设计

基于ZigBee定位与无线数据传输技术,设计了一种针对养老机构的老年人移动体征监测系统。该系统可实现体征（脉搏、心电、血氧）监测、人体定位与紧急情况报警。基于脉搏信号的移动采集与存储实验验证了该系统的有效性,脉搏测量范围为（50-170）次/分,测量平均误差小于3%,定位平均误差小于4 m,系统数据传输速率为250 kbps。该系统可有效实时地对养老机构中的老年人的健康与安全状况进行监护,对老年人生命安全保障具有重要意义。     

Relation of neutrophil-to-lymphocyte ratio to acute kidney injury in patients with sepsis and septic shock: A retrospective study

BackgroundThe purpose of this study was to determine the association of the neutrophil-to-lymphocyte ratio (NLR) measured at the time of admission to intensive unit (ICU) with acute kidney injury (AKI) in patients with sepsis and septic shock. In addition, we investigated whether the NLR affects in-hospital mortality in septic AKI patients.MethodsIn this retrospective study, a total of 222 adult patients with sepsis and septic shock were included, who were admitted to the ICU of Zhongnan Hospital of Wuhan University from January 2015 to December 2017. Sepsis and septic shock were diagnosed based on sepsis-3 consensus. AKI was diagnosed according to the KDIGO-AKI criteria. The primary outcome of the study was septic AKI. The secondary endpoint was in-hospital mortality of patients with septic AKI.Results132 patients (59.46%) had AKI, and 64 (28.83%) died, of whom 55 (41.67%) in the AKI group and 9 (10.00%) in the non-AKI group. The NLR of the AKI group was significantly higher than that of the non-AKI group, and there was a statistically significant difference between the two groups (P < 0.001). Multivariate logistic regression analysis suggested that the NLR was independent predictors of septic AKI (OR = 1.047, 95% CI: 1.005–1.091, P = 0.026). The ROC curve showed that the AUC of the NLR for predicting septic AKI was 0.656 (95% CI 0.584–0.728, P < 0.001) and the cutoff value was 17.11 (sensitivity, 62.1%; specificity, 68.9%). However, no correlation was found between the NLR and in-hospital mortality in septic AKI patients.ConclusionNLR, a laboratory variable that is simple, widely available and inexpensive, was associated with the development of septic AKI and may be potential for risk stratification of septic AKI.     

新型肿瘤标志物:Mu-GlcNAc

作者发现了一个新的肿瘤标志物MA153,其化学结构为Mu-GlcNAc（粘蛋白1-N-乙酰氨基葡萄糖）,它可与单克隆抗体Ma695和相关Aptamer（适配体MA153-A）形成Ma695-Mu-GlcNAc-MA153-A式的夹心反应。临床血清学检测表明,Mu-GlcNAc存在于癌症患者血中,以1U/mL为正常界值,Mu-GlcNAc的肿瘤特异度达95%,癌症检出的灵敏度对乳腺癌、胰腺癌、肝癌、肺癌、食管癌、口腔癌、结肠癌、胆管癌、卵巢癌、宫颈癌、子宫癌,分别为80%、74%、68%、70%、75%、50%、60%、55%、70%、64%、60%。本研究资料显示,Mu-GlcNAc是一个新的良好广谱肿瘤标志物。     

2020年7月全球传染病疫情概要

2020年7月全球共监测到传染病63种,涉及217个国家和地区。 除流感外,涉及国家和地区数量位于前5位的传染病分别为新型冠状病毒肺炎（217个）、登革热（35个）、麻疹（15个）、霍乱（8个）和基孔肯雅热（8个）。 病死率位于前4位的传染病分别为埃博拉病毒病（43.1%）、鼠疫（21.9%）、拉沙热（20.8%）和新型冠状病毒肺炎（4.0%）。 死亡病例数位于前5位的传染病分别为新型冠状病毒肺炎、霍乱、登革热、麻疹和埃博拉病毒病。 亚洲主要流行新型冠状病毒肺炎和登革热;非洲主要流行新型冠状病毒肺炎、埃博拉病毒病、鼠疫、霍乱、黄热病、拉沙热和麻疹;美洲主要流行新型冠状病毒肺炎和登革热;欧洲主要流行新型冠状病毒肺炎和麻疹。     

HPLC-MS/MS 法在检测慢性粒细胞白血病患者帕纳替尼血药浓度中的应用

目的　建立测定慢性粒细胞白血病(chronic myelogenous leukemia, CML) 患者血浆帕纳替尼浓度的高效液相色谱- 串联质谱法（HPLC-MS/MS）,并应用于帕纳替尼血药浓度日常监测,为帕纳替尼合理使用提供实验室依据。方法　采用含内标（帕纳替尼-d8）的甲醇对患者血浆进行沉淀蛋白处理。色谱柱为Ultimate XB-C18,柱温60℃,流动相为甲醇相（0.1% 甲酸）和水相（0.1% 甲酸和2 mmol/L 乙酸铵）,梯度洗脱。质谱检测方式为电喷雾离子阱正离子模式,MRM 扫描,同时监测帕纳替尼m/z 533.1>260.1 和帕纳替尼-d8 m/z 541.2>260.1。采用内标法定量,以帕纳替尼和帕纳替尼-d8 峰面积比为定量依据,计算血浆帕纳替尼浓度,并分别对其线性、专属性、精密度、准确度及稳定性进行考察。结果　帕纳替尼浓度在（1 ～ 250） ng/ml 范围内与峰面积线性关系良好,Y = 0.019 3X + 0.028 4 （r= 0.999 1）。专属性较好,血浆中的内源性物质不干扰帕纳替尼及其内标的测定;日内及日间RSD 均小于5%;相对回收率为100.91%~105.18%;室温放置稳定性及冻融稳定性RSD 均小于5%。结论　该文建立的HPLC-MS/MS 法,前处理简单,特异度及灵敏度高,能准确、快速地检测血浆帕纳替尼浓度,适合慢性粒细胞白血病患者帕纳替尼血药浓度的日常监测。