Metabolomic approach to understand the acute and chronic hepatotoxicity of Veratrum nigrum extract in mice based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry

Veratrum nigrum L. (VN) is a poisonous traditional Chinese medicine herb present since thousands of years in China. Clinical studies have shown that VN has the ability to cause hepatotoxicity, which severely limits its clinical use. The mechanism of its hepatotoxicity has not been fully elucidated. The purpose of this study was to develop and characterize a model of acute and chronic hepatotoxicity induced by Veratrum nigrum L. extract (VNE) to understand the mechanism of liver tissue metabolomics approach using on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS). Mice were administered with VNE in the acute and chronic phases. Histopathologic inspections and biochemistry analysis disclosed severe liver damage after exposure to VNE. A partial least-squares discriminant analysis (PLS-DA) of the metabolomic profiles of rat liver tissues highlighted a number of metabolic disturbances induced by VNE, focusing on purine and pyrimidine metabolism, tryptophan metabolism, phospholipid metabolism, sphingolipid metabolism and fatty acid metabolism. These findings could well explain VNE-induced acute and chronic hepatotoxicity and reveal several potential biomarkers associated with this toxicity. This indicates that UHPLC-Q-TOFMS-based metabolomics approach demonstrated its feasibility and allowed a better understanding of VNE-induced liver toxicity dynamically.     

Remote Postconditioning Induced by Trauma Protects the Mouse Heart against Ischemia Reperfusion Injury. Involvement of the Neural Pathway and Molecular Mechanisms

Purpose

Abdominal superficial surgical incision elicits cardioprotection against myocardial ischemia reperfusion (I/R) injury in mice. This cardioprotective phenomenon, termed remote preconditioning of trauma (RPCT), results in an 80 to 85 % reduction in cardiac infarct size. We evaluated cardioprotection and the molecular mechanisms of remote postconditioning of trauma (RPostCT) in a murine I/R injury model.

Methods

Mice were analyzed using a previously established I/R injury model. An abdominal superficial surgical incision was made 45 min after myocardial ischemia at the end of coronary occlusion, and infarct size was determined 24 h after reperfusion.

Results

The results indicated that a strong cardioprotective effect occurred during RPostCT (56.94 ± 2.71 % sham vs. 15.58 ± 2.16 % RPostCT; the mean area of the infarct divided by the mean area of the region at risk; p ≤ 0.05; n = 10). Furthermore, pharmacological intervention revealed neurogenic signaling involvement in the beneficial effects of RPostCT via sensory and sympathetic thoracic nerves. Pharmacological experiments in transgenic mice demonstrated that bradykinin receptors, β-adrenergic receptors (AR), and protein kinase C were implicated in the cardioprotective effects of RPostCT.

Conclusions

RPostCT significantly decreased myocardial infarction size via neurogenic transmission and various signaling pathways. This study describes a new cardiac I/R injury prevention method that might lead to the development of therapies that are more clinically relevant for myocardial I/R injury.

     

Histologic features and genomic alterations of primary colorectal adenocarcinoma predict growth patterns of liver metastasis

BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established.AIM To assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis.METHODS A total of 29 patients with paired resections of both primary CRC and liver metastasis were divided into two groups:A(15 cases with desmoplastic liver metastasis)and B(14 cases with replacement liver metastasis).Clinical information was obtained from patients’charts.Mismatch repair proteins,BRAFV600E,and PD-L1 were evaluated by immunohistochemistry.Five cases were selected randomly from each group for whole exome sequencing(WES)analysis.RESULTS In the primary tumor,expanding growth pattern,low tumor budding score(TBS),and Crohn’s disease-like response(CDR)were associated with desmoplastic liver metastasis and better overall survival,whereas infiltrating growth pattern alone of primary carcinoma could predict the replacement liver metastasis and worse overall survival(P<0.05).On WES analysis,primary carcinoma with desmoplastic liver metastasis showed mutations in APC(4/5);TP53(3/5);KRAS,PIK3CA,and FAT4(2/5);BRCA-1,BRCA2,BRAF,and DNAH5(1/5),whereas primary carcinoma with replacement liver metastasis showed mutations in APC and TP53(3/5);KRAS,FAT4,DNH5,SMAD,ERBB2,ERBB3,LRP1,and SDK1(1/5).CONCLUSION The HGPs,TBS,and CDR of primary CRC as well as the presence of specific genetic mutations such as those in PIK3CA could be used to predict the HGPs of liver metastasis,response to therapy,and patients’prognosis.     

区域医疗与PACS网络系统建设的决策意义

本文探索区域医疗PACS络系统建设的决策意义。区域PAcs是从区域卫生信息化建设大局出发,以区域内代表性医院为核心,通过构造区域内部的医学影像信息交换平台,以实现区域内医院的医学影像资源的共享与整合。运行3年来,区域医疗中心与PAcs网络系统建设使区域医学影像信息得以共享,提升了现代化医院建设,提升了区域医疗质量和管理水平。     

Study on the expression of CD14 + CD16 + monocytes and VEGF in peripheral blood of patients with type 2 diabetes mellitus and diabetic macroangiopathy

International Journal of Diabetes in Developing Countries - To study the expression of CD14 + CD16 + monocytes and VEGF and the levels of serum adiponectin and MCP-1 in peripheral blood...     

等离子扁桃体手术与超声刀扁桃体手术组织损伤与疼痛的对照研究

目的比较低温等离子扁桃体手术与超声刀扁桃体手术的效果,为临床应用提供参考。方法选取2014年1月—2017年4月在复旦大学附属上海市第五人民医院耳鼻喉科行扁桃体切除术的成年患者共304例,采用电脑生成随机数方法随机分为等离子手术组155例和超声刀手术组149例。记录2组患者手术时间、手术出血情况、住院时间,测量组织损伤深度,对2组患者术后1~10 d每天休息时与吞咽时的VAS疼痛评分进行多元线性回归分析。结果等离子手术组手术时间为(20.2±7.5)min,超声刀手术组为(16.7±6.3)min,超声刀手术组手术时间明显短于等离子手术组(P<0.05)。2组术后近期出血(<24 h)发生率分别为3.2%(5/155)、1.3%(2/149),远期出血(>24 h)发生率分别为7.7%(12/155)、1.3%(2/149),等离子手术组远期出血发生率明显高于超声刀手术组(P<0.05)。2组组织损伤深度及术后住院时间比较差异均无统计学意义(P均>0.05)。等离子手术组休息时疼痛评分达到3分的时间相比超声刀手术组缩短了1.94 d,吞咽时疼痛评分达到3分的时间则缩短了2.02 d。结论超声刀扁桃体手术术后远期出血概率明显小于等离子扁桃体手术,但等离子扁桃体手术患者术后疼痛减轻时间相比超声刀扁桃体手术患者约快2 d。     

Does right lateral decubitus position change retroperitoneal oblique corridor? A radiographic evaluation from L1 to L5

Purpose

To determine if the retroperitoneal oblique corridor will be affected by right lateral decubitus position.

Methods

Forty volunteers were randomly enrolled and MRI scan was performed from L1 to L5 in supine and right lateral decubitus positions, respectively. In images across the center of each disc, O was defined as the center of a disc and A (supine) or A′ (right lateral decubitus) was located in left lateral border of the aorta or the iliac artery; B (supine) or B′ (right lateral decubitus) was on the anterior medial border of the psoas. The distance of AB and A′B′ (Recorded as A-Ps and A-Pr, respectively) at each level was recorded and compared to each other. The relationships between A-Pr, sex, BMI and relative psoas cross-sectional area (PCSA) at each level were also evaluated.

Results

A-Pr was significantly smaller than A-Ps at L1/2, L2/3 and L3/4 (All p < 0.05); there was no significantly difference of A-Pr between all levels (p = 0.105), but L1/2 seemed to be larger than L3/4, followed by L2/3 and L4/5; A-Pr at each level was not affected by sex (All p > 0.05); linear relationships were found between A-Pr, BMI and PCSA at L1/2 and L3/4.

Conclusions

ROC at L1/2, L2/3 and L3/4 will significantly decrease from supine to right lateral decubitus position and the reason may be due to the relaxed psoas deformation. Using MRI images in supine position for pre-operatively ROC evaluation is not accurate. Spine surgeon should also be more cautious when OLIF is performed at L4/5 where ROC is the smallest. Patients from Asia and those with strong psoas major at L1/2 and L3/4 are also associated with relatively narrow ROC.

     

Repetitive nerve stimulation as a diagnostic aid for distinguishing cervical spondylotic amyotrophy from amyotrophic lateral sclerosis

Purpose

To identify and compare the features of compound muscle action potential (CMAP) decrements in repetitive nerve stimulation (RNS) in patients with cervical spondylotic amyotrophy (CSA) and in patients with amyotrophic lateral sclerosis (ALS).

Methods

The cohort consisted of 43 CSA (distal-type to proximal-type ratio: 27–16) and 35 ALS patients. Five muscles, including abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps brachii (BB), middle deltoid (Del), and upper trapezius (Trap), were tested by 3-Hz RNS. Decrements greater than cutoff values (APB > 5.8%; ADM > 4.8%; BB > 5.2%; Del > 6%; Trap > 5.1%) determined using receiver operating characteristic (ROC) curves were defined as abnormal, and the conventional criterion (≥10%) was also considered.

Results

A significant CMAP decrement (>cutoff values) was recorded from at least one tested muscle in 91.4% of ALS patients, and was most common in the proximal muscle, a finding that differed significantly from CSA patients (32.6%, P < 0.05). The application of cutoff values greatly improved the sensitivity of RNS over the conventional criterion (≥10%) for the detection of ALS (P < 0.05). The specificity of this technique remained higher when performing RNS in the proximal muscles, especially in the upper trapezius (AUC = 0.864, sensitivity = 0.643, and specificity = 1.000). The decrement percentages were significantly greater in the proximal muscles of ALS patients than in those of the CSA patients (P < 0.05). In addition, illness duration was not correlated with decrement percentage in either patient group, and no difference in the frequency of decrement among different ALS diagnostic categories was observed (P > 0.05).

Conclusions

The application of RNS, especially in proximal muscles, may provide a simple accurate and noninvasive supplementary test for distinguishing CSA from ALS, even in the early stage of these diseases. A combination of RNS, needle EMG, clinical features and cervical magnetic resonance imaging may yield sufficient diagnostic information to differentiate CSA and ALS.

     

生存素反义寡核苷酸对人子宫内膜癌细胞增殖的抑制作用

 目的 探讨生存素（survivin）反义寡核苷酸（antisense oligonucleotide,ASODN）对人子宫内膜癌细胞HEC-1B增殖的抑制作用。方法 实验分空白对照组（control组）、单纯脂质体对照组（Lip组）、正义链转染对照组（SODN组）、ASODN转染组（ASODN组）4组。人工合成正、反义寡核苷酸,经脂质体将survivin正、反义寡核苷酸转染入子宫内膜癌细胞48 h后收集各组细胞。免疫印迹（Western blot）法检测各组细胞生存素表达情况,流式细胞仪检测各组细胞凋亡率,四甲基偶氮唑蓝试验（MTT）法检测细胞生长抑制情况。结果 脂质体介导生存素反义寡核苷酸转染后的子宫内膜癌细胞出现生存素蛋白表达明显下降;ASODN转染组细胞凋亡率和增殖抑制率均明显高于各对照组（P<0.05）,而各对照组间差异无统计学意义（P>0.05）。结论 生存素反义寡核苷酸转染子宫内膜癌细胞能下调生存素蛋白表达,诱导子宫内膜癌细胞凋亡,抑制细胞增殖,对子宫内膜癌是一种有效的基因疗法。