进展型脑梗死患者miRNA的表达水平及临床意义

目的探讨进展型脑梗死患者微小RNA(miRNA)的表达水平及临床意义。方法回顾性分析2016年7月至2018年7月期间我院收治的138例脑梗死患者病例资料。根据斯堪的那维亚卒中量表(SSS)将其分为对照组(稳定型脑梗死,82例)和观察组(进展型脑梗死,56例)。观察组患者按照高级中枢损伤严重程度评定标准(MESSS)评分为轻度进展(30例)、中度进展(17例)、重度进展(9例)三个亚组。对观察组出院两个月后进行预后随访,并将其分为预后不良组及预后良好组。分析进展型脑梗死患者miRNA的表达水平及临床意义。结果进展型脑梗死患者的miRNA-21、miRNA-223水平均显著高于稳定型脑梗死患者(P 0. 05); miRNA-21、miRNA-223的高表达均是进展型脑梗死的危险因素(P 0. 05),且进展型脑梗死的严重程度与血清miRNA-21、miRNA-223的表达水平均呈正相关(r=0. 834,P=0. 008;r=0. 896,P=0. 001)。预后不良组患者血清miRNA-21、miRNA-223表达水平显著高于预后良好组(P 0. 05);血清miRNA-21、miRNA-223表达水平预测进展型脑梗死预后的AUC面积分别为0. 805、0. 834,并分别得出截断值4. 45 (敏感度77. 14%,特异性82. 28%)、7. 06(敏感度82. 86%,特异性73. 42%)。结论进展型脑梗死患者miRNA-21、miRNA-223呈高表达,且其表达水平与脑梗死严重程度呈正相关,同时对预测进展型脑梗死预后均具有较高的敏感度和特异度,有可能成为一种早期诊断和预测进展型脑梗死生物标志物。     

A Burnout Reduction and Wellness Strategy: Personal Financial Health for the Medical Trainee and Early Career Radiation Oncologist

PurposePhysician burnout is reported in more than one out of every 2 practicing clinicians and is just as prevalent in training physicians. Burnout severity is also associated with increasing levels of financial debt. Medical professionals are notable for their high and increasing levels of debt; despite this, financial literacy is poor among physicians, and financial education is largely absent from medical education. Radiation oncologists (ROs) are no different in this regard, with 33% of residents reporting high levels of burnout symptoms, 33% carrying >$200,000 of educational debt, and 75% reporting being unprepared to handle future financial decisions. To fill this gap, we reviewed the basic tenets of personal financial health for the early career RO.Methods and materialsThe core concept of financial independence (FI) is introduced, and we review 4 basic tenets of personal financial health for the young medical professional: debt, behavior, investment, and asset protection strategies.ResultsFI is achieved by saving until the desired quality of life can be maintained, independent of employment income. Debt strategy involves minimizing debt accrual, understanding student loans, and having a debt management plan. Behavioral strategy involves setting financial goals, calculating worth and a savings rate, budgeting, and frugal living. The basics of investing include asset allocation, diversification, rebalancing, and minimizing expenses. Finally, asset protection includes insuring against catastrophic events with disability, life, health, liability, and property insurance.ConclusionsHealthy financial practices can lead to FI and may facilitate professional and personal freedoms with the goal of mitigating burnout-associated stressors. The tenets of strong financial health for ROs in the early stages of their career include sound debt, behavioral, investment, and asset protection strategies. Furthermore, initial and continuing financial education is an overlooked but important curriculum component. ROs with their financial houses in order can devote more resources to learning and practicing good medicine while living healthy, rewarding lives.     

ZDY101和SZ201对α-分泌性淀粉样前体蛋白生成的影响

目的探讨ZDY10 1和SZ2 0 1及二者不同配比联合应用对HEK2 93sw细胞生成α -分泌性淀粉样前体蛋白的影响。　方法用Westernblot法检测HEK2 93sw细胞生成的α -sAPP含量 ,观察ZDY10 1、SZ2 0 1及二者不同配比联合应用在 2 4～ 48h、48～ 72h时段内α -sAPP生成量的变化。　结果 2 4～ 48h时段的实验中 ,ZDY10 1和SZ2 0 1浓度分别为 1× 10 - 5mol L时 ,α -sAPP含量分别为 2 .0 6± 0 .73、2 .6 4± 1.2 1,明显高于DMSO对照组的 1.0 0(P <0 .0 1) ;48～ 72h时段的实验中 ,ZDY10 1和SZ2 0 1单独应用且浓度分别为 1× 10 5mol L时 ,α -sAPP含量也明显高于DMSO对照组的 1.0 0 (P <0 .0 1)。二者相加的效果高于ZDY 10 1、SZ2 0 1单独应用 (P <0 .0 5 )。如果二者联合应用 ,降低各自的浓度 ,总浓度仍为 1× 10 - 5mol L时 ,提高α -sAPP含量的效果不明显。　结论ZDY10 1、SZ2 0 1在一定浓度时 ,能增加α -sAPP的生成 ,二者联合应用效果更强。     

用大肠杆菌CM89菌株对三种化学物抗突变作用的研究

本文以 E.coli CM891为靶细胞,用细菌内抗突变作用模式研究了肉桂醛,鞣酸,二烯丙三硫的抗4NQO 突变性及其作用机制。含质粒 pKM101的 CM891的高抗株(抗50μg/ml 氨苄青霉素)能提高该菌株的自发突变率和4NQO 诱发的突变率以及对鞣酸的杀伤抗性。肉桂醛的抗突变性不依赖质粒 pKM101效应,但与暂时性生长延搁有关。鞣酸及二烯丙三硫的抗突变机制可能包括质粒 pKM101介导的易误修复。上述三种化学物中每二种联合应用均显示抗4NQO 突变性的协同效应及对靶细胞的毒性杀伤作用。     

复方脑得生中总黄酮纯化工艺研究

目的研究复方脑得生中总黄酮的最佳纯化工艺。方法采用正交设计和单因素试验法，以总黄酮的洗脱率和含量为指标，考察利用D-101树脂富集、纯化复方脑得生中总黄酮的工艺条件及参数。结果优选纯化工艺为：上样溶液浓度0．1g／mL，流速2aV／h，树脂径高比1：7；吸附后，先用5BV的水洗脱，再用5BV40％乙醇洗脱。所得提取物中总黄酮的含量为80．57％，总黄酮转移率达83．76％。结论优选纯化工艺得到的总黄酮含量高，工艺简单，适宜工业化生产。     

SNHG6靶向miR-101/TGFBR1促进AMI小鼠左心室心肌纤维化

目的探讨SNHG6对急性心肌梗死(AMI)小鼠左心室心肌的影响。 方法将30只雄性C57/BL6小鼠构建成AMI小鼠后随机均分为AMI组、AMI+SNHG6组、AMI+miR-101-3p组、AMI+SNHG6+miR-101-3p组、AMI+miR-101-3p+TGFBR1组,另设正常小鼠6只为假手术组。qRT-PCR检测AMI小鼠SNHG6、miR-101-3p表达水平。心脏彩超检测各组小鼠左室射血分数(LVEF);马松和天狼星红染色法以及免疫组化分析各组小鼠左心室心肌纤维化变化。将H9C2细胞株分为阴性对照组(转染空质粒)、SNHG6组(转染质粒SNHG6)、miR-101-3p组(转染质粒miR-101-3p)。Western blotting检测各组TGFBR1蛋白表达;采用双荧光素酶报告基因法预测并验证SNHG6/miR-101-3p/TGFBR1荧光素酶活性及调控机制。 结果AMI小鼠较假手术组SNHG6表达显著增加,miR-101-3p降低(P＜0.05)。与AMI组比较,AMI+SNHG6组小鼠LVEF降低,心肌纤维化程度加重(P＜0.05);AMI+miR-101-3p组LVEF升高,心肌纤维化程度减轻(P＜0.05)。AMI+SNHG6+miR-101-3p组较AMI+SNHG6组LVEF升高、心肌纤维化程度减轻(P＜0.05),而AMI+miR-101-3p+TGFBR1组较AMI+miR-101-3p组LVEF降低、心肌纤维化程度加重(P＜0.05)。双荧光素酶报告基因法验证显示,miR-101-3p组SNHG6、TGFBR1野生型质粒的荧光素酶活性较阴性对照组明显降低(P＜0.05)。 结论SNHG6抑制miR-101-3p上调TGFBR1加重AMI小鼠左心室心肌纤维化。     

TAC-101, a benzoic acid derivative, inhibits liver metastasis of human gastrointestinal cancer and prolongs the life-span

We examined the anti-tumor effect of a novel benzoic acid derivative, TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid) on models with liver metastasis. Oral administration of TAC-101 significantly inhibited spontaneous liver metastasis of AZ-521 (human gastric cancer ) by orthotopic implan-tation to athymic nude mice. It also inhibited both the liver metastasis of AZ-521 induced by intrasplenic injection and the secondary lung metastasis from the liver. In addition, TAC-101 inhibited the proliferation of Co-3 (human colon adenocarcinoma) that formed a single nodule in the liver of athymic nude mice by intrahepatic implantation. The growth inhibitory effect of TAC-101 on AZ-521 experimental liver metastasis was observed when treatment was started on day 7, 14, or 21 which may correspond to the progressive stage of liver metastasis in clinical settings. Multiple administration of TAC-101 (8 mg/kg/day) significantly prolonged survival time of the animals with liver met astasis by intrasplenic injection of AZ-521 (T/C = 230%) and A549 (human lung adenocarcinoma; T/C = 186%). These effects of TAC-101 were stronger than those of 5-FU, CDDP or ATRA. Furthermore, TAC-101 inhibited the binding of AP-1 to DNA on electrophoretic mobility shift assay using nuclear extract of AZ-521 cells, although ATRA did not inhibit. These findings suggested that TAC-101 may be a candidate for a new class of anti-cancer agents for liver metastasis. © Rapid Science Ltd.     

Selective PI3Kδ inhibitors,a review of the patent literature

Introduction: Phosphatidylinositol 3-kinase (PI3K), a lipid kinase, is the first kinase involved in, and a key component of, the PI3K/Akt/mTOR signalling pathway, and is significantly upregulated in many cancers. However, four distinct isoforms of PI3K are known with different expression patterns and different pathophysiological roles. The PI3Kδ isoform is expressed in leukocytes and has been implicated as a potential target in the development of selective inhibitors for the treatment of haematological malignancies and various inflammatory diseases.

Areas covered: This review briefly covers the understanding of the four PI3K isoforms and their roles and the inhibitors selective for either one or two isoforms that have been identified to date. It then focuses upon progress in the identification of selective PI3Kδ inhibitors focusing upon the original efforts at ICOS/Calistoga that led to the initial clinical candidates such as CAL-101. After assessing the patent filings from these companies, it considers filings from other players and how they have sought to explore similar, and structurally distinct, scaffolds in their search for selective inhibitors, and how different companies appear focused on either oncological or anti-inflammatory uses for their inhibitors.

Expert opinion: The impact of the work at ICOS is highlighted by the fact that prior to their disclosure of selective leads, no patent applications claiming selective PI3Kδ inhibitors had been filed by other companies. This disclosure, followed by the first filings by Piramed, led to an upsurge in interest with a large cluster of filings published in 2008 while half the relevant applications were published in 2010 or 2011. These efforts, and the initial clinical data on CAL-101, the leading PI3Kδ inhibitors, have also prompted a number of commercially significant deals. In addition to an increasing number of filings, the entry into the clinical development of more selective PI3Kδ inhibitors should stimulate a better understanding of the role of this specific kinase isoform.