Phospho-Aspirin (MDC-22) inhibits pancreatic cancer growth in patient-derived tumor xenografts and KPC mice by targeting EGFR: Enhanced efficacy in combination with irinotecan

Novel therapeutic strategies are needed in the fight against pancreatic cancer. We have previously documented the chemopreventive effect of MDC-22 in preclinical models of pancreatic cancer. In the present work, we examined the therapeutic effects of MDC-22 in patient-derived tumor xenografts (PDTXs) and in LSL-Kras^G12D/+, LSL-Trp53^R172H/+, Pdx1-Cre (KPC) genetically engineered mice, two complementary and clinically relevant animal models of pancreatic cancer. In addition, we evaluated whether MDC-22 could synergize with current chemotherapeutic drugs used in the clinic. MDC-22 reduced the growth of various human pancreatic cancer cell lines in a concentration-dependent manner. In vivo, MDC-22 strongly reduced patient-derived pancreatic tumor xenograft growth by 50%, and extended survival of LSL-Kras^G12D/+; LSL-Trp53^R172H/+; Pdx1-Cre (KPC) mice by over a month (5.3 months versus 7.0 months). In both models, MDC-22 inhibited EGFR activation and its downstream signals, including ERK and FAK phosphorylation. In human pancreatic cancer cell lines, MDC-22 enhanced the growth inhibitory effect of irinotecan, and to a lesser degree those of gemcitabine and nab-paclitaxel. Normal human pancreatic epithelial cells were more resistant to the cytotoxic effects of, both, MDC-22 alone or in combination with irinotecan, indicating selectivity. Furthermore, MDC-22 enhanced irinotecan''s effect on cell migration, in part, by inhibiting EGFR/FAK signaling. Collectively, our results indicate that MDC-22 is an effective anticancer drug in preclinical models of pancreatic cancer, and suggest that MDC-22 plus irinotecan as drug combination strategy for pancreatic cancer treatment, which warrants further evaluation.     

基于NLRP3信号通路探究天麻素注射液联合神经节苷脂辅助治疗 脊髓损伤的可能机制

基于NOD样受体热蛋白结构域相关蛋白3（NLRP3）信号通路探究天麻素注射液联合神经节苷脂辅助治疗脊髓损 伤（SCI）的可能机制。【方法】 将108例SCI患者随机分为观察组和对照组,每组各54例。2组患者均给予常规康复训练,在此 基础上,对照组给予神经节苷脂治疗,观察组给予天麻素注射液联合神经节苷脂治疗。30 d为1个疗程,连续治疗2个疗程。 比较2组患者的肌力恢复正常时间、可下地行走时间和留院观察时间,观察2组患者治疗前后美国脊柱损伤协会（ASIA）评分 及血清脑源性神经生长因子（BDNF）、中枢神经特异性蛋白（S-100β）、白细胞介素（IL）-1β、IL-18及NLRP3、半胱氨酸蛋白 酶1（Caspase-1）、凋亡相关斑点样蛋白（ACS）水平的变化情况,并评价2组患者的临床疗效及安全性。【结果】（1）治疗2个疗 程后,观察组的总有效率为 83.33%（45/54）,对照组为 66.67%（36/54）,组间比较（χ2检验）,观察组的疗效明显优于对照组 （P＜0.05）。（2）治疗后,观察组的肌力恢复正常时间、可下地行走时间及留院观察时间均较对照组明显缩短（P＜0.01）。 （3）治疗 1 个和2个疗程后,2组患者ASIA的痛觉、运动、触觉评分均较治疗前明显升高（P＜0.05）,且治疗2个疗程后又较 治疗 1个疗程后升高（P＜0.05）;组间比较,观察组在治疗 1个和 2个疗程后对 ASIA的痛觉、运动、触觉评分的升高幅度均 明显优于对照组（P＜0.05）。（4）治疗1个和2个疗程后,2组患者的血清BDNF水平均较治疗前升高（P＜0.05）,NLRP3、ACS、 Caspase-1蛋白和血清IL-1β、IL-18、S-100β水平均较治疗前下降（P＜0.05）,且治疗2个疗程后血清BDNF水平又均较治疗 1 个疗程后升高（P＜0.05）,NLRP3、ACS、Caspase-1 蛋白和血清 IL-1β、IL-18、S-100β 水平又均较治疗 1 个疗程后下降 （P＜0.05）;组间比较,观察组在治疗1个和2个疗程后对血清BDNF水平的升高幅度及对NLRP3、ACS、Caspase-1蛋白和血 清IL-1β、IL-18、S-100β水平的下降幅度均明显优于对照组（P＜0.05）。（5）治疗过程中,2组患者均未出现药物相关不良反 应。【结论】 天麻素注射液联合神经节苷脂治疗 SCI患者疗效确切,可通过调控炎症小体 NLRP3信号通路,减轻神经炎症反 应,促进神经功能恢复,其疗效优于单纯神经节苷脂治疗。     

黑逍遥散对APP/PS1双转基因小鼠海马和脑皮层CaMKⅡα蛋白及其磷酸化表达的影响

目的:观察黑逍遥散对阿尔茨海默症(AD)小鼠海马和脑皮层钙调蛋白依赖性激酶2α(CaMKⅡα)及其磷酸化表达水平的干预效应。方法:30只APP/PS1双转基因雄性小鼠称体质量并按随机原则分为模型组、盐酸多奈哌齐组、黑逍遥散组,每组10只。同月龄、同种系的野生型C57BL/6雄性小鼠10只为空白组。盐酸多奈哌齐组(6 g·kg~(-1))、黑逍遥散组(3. 25 mg·kg~(-1))分别连续给药90 d后,Morris水迷宫检测行为学变化,免疫组化和蛋白免疫印迹法检测小鼠海马区和脑皮层CaMKⅡα蛋白及其磷酸化的表达。结果:干预90 d后,与空白组比较,AD模型组小鼠,逃避潜伏期显著延长,跨原平台和有效区域次数显著减少(P 0. 01),小鼠海马区及脑皮层Ca MKⅡα蛋白表达显著减弱或降低,而p-CaMKⅡα蛋白表达显著升高(P 0. 05,P 0. 01);与模型组比较,盐酸多奈哌齐和黑逍遥散组小鼠的逃避潜伏期均显著缩短、跨原平台次数均显著增加(P 0. 01),小鼠海马区及脑皮层Ca MKⅡα蛋白显著增强或升高,p-CaMKⅡα蛋白表达显著降低(P 0. 05,P 0. 01)。结论:黑逍遥散通过调节AD小鼠不同脑区参与细胞记忆形成机制的关键蛋白Ca MKⅡα及其磷酸化表达,进而发挥改善AD小鼠的学习记忆能力。     

中医导引研究综述

导引是中医临床常用方法之一,在防治疾病和养生康复方面发挥着重要作用。就中医导引的文献研究、临床研究、基础研究和历史研究做一综述,梳理其发展现状。     

经皮穿刺置管引流联合生长抑素治疗胰腺假性囊肿

胰腺假性囊肿(pancreatic pseudocyst,PPC)是胰腺炎和胰腺外伤后常见的并发症。胰腺假性囊肿的并发症包括感染、出血及囊肿破裂等,一旦发生,后果严重,治疗困难。近年报道采用超声或CT引导     

Application of bone metabolic parameters in the diagnosis of growing pains

ObjectiveThe present study aimed to assess the diagnostic significance of serum bone metabolic parameters in children with growing pains (GPs).MethodsAll patients diagnosed with GP and healthy controls matched with age and gender were recruited at the outpatient clinic of Children''s Hospital at Zhejiang University School of Medicine from August 2016 to August 2021. In all subjects, serum levels of calcium (Ca), phosphorus (P), procollagen type‐I N‐terminal (PINP), parathormone (PTH), 25‐hydroxyvitamin D (25‐(OH)D), osteocalcin (OC), N‐terminal cross‐linked telopeptides of type‐I collagen (CTX), and tartrate‐resistant acid phosphatase type 5b (TRACP5b) were investigated. The univariate analysis, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve were used to identify the bone metabolic parameters factors for diagnosing GP.ResultsWe enrolled 386 children with GP and 399 healthy controls in present study. The mean age of GP group was 5.319 years, and, primarily, the subjects were preschool‐age children. The gender ratio (male‐to‐female) was 1.27 in GP group. After adjusting for age and gender, we identified that the serum levels of Ca (p < 0.001, OR: 25.039), P (p = 0.018, OR: 2.681), PINP (p < 0.001, OR: 1.002), and PTH (p = 0.036, OR: 0.988) were independent diagnostic factors associated with GP. Area under curve (AUC) of the ROC curves was in the order: PINP (0.612) > Ca (0.599) > P (0.583) > PTH (0.541). A combination of independent diagnostic factors and multivariable logistic regression analysis provided a refined logistic regression model to improve the diagnostic potential, of which the AUC had reached 0.655.ConclusionsSerum levels of Ca, P, PINP, and PTH could be independent diagnostic factors associated with GP. The logistic model was significantly superior to bone metabolic parameters for diagnosing GP.     

毛细管电泳和质谱联用在线预浓缩酚酸类化合物及其抗氧化活性评价

目的 建立一种新型高效的毛细管电泳和质谱联用（CE-MS）在线预浓缩方法,用于检测丹参样品中酚酸类化合物中4种亲水活性成分（丹参素、丹酚酸B、咖啡酸和紫草酸）,并对其抗氧化活性作出评价。方法 利用CE-MS在线预浓缩技术,采用未涂层石英毛细管柱（90 cm × 50 μm）,电压：27 kV。样品的进样压力：50 mbar,进样时间：3～300 s,毛细管温度：25 ℃。鞘液：5 mmol·L-1的乙酸氨溶液（甲醇溶解）,流速：4 mL·min-1。结果 该技术灵敏度比通常的流体注射提高了30～50倍。结论 该方法可用于分析丹参药材中丹参素、丹酚酸、咖啡酸、紫草酸等酚酸类化合物,也可以用于评价丹参样品中酚酸类化合物的抗氧化成分。     

梗阻性黄疸对患者体内右美托咪定药动学的影响

目的 建立超高效液相色谱-串联质谱法测定人血浆右美托咪定的浓度,评价梗阻性黄疸对患者体内右美托咪定药动学参数的影响.方法 样品经液-液萃取后测定,色谱柱为Agilent Eclipse Plus C18,流动相为甲醇?0.1％甲酸水溶液,流速为0.2 ml/min,柱温为35℃,质谱检测采用动态多反应离子检测模式.结果...     

劳绍贤辨治胃痞的数据挖掘分析和经验总结

目的 分析劳绍贤教授辨治胃痞的用药规律。方法 收集劳绍贤教授于2017年3月至2022年3月期间治疗胃痞患者的有效处方,提取患者一般资料、主诉、诊断、辨证分型、处方等。采用Excel软件和古今医案云平台（V 2.3.7）工具,构建处方数据库,利用其数据挖掘功能对处方进行证型分析、中药使用频次和属性分析,以及药物关联规则分析、聚类分析等。结果 共纳入272首处方,涉及164味药物。中医证型以湿热证、气滞证为主;使用频次≥30次的中药有25味,代表性药物为法半夏、甘草、陈皮、紫苏梗、木香;药性主要是温性、平性;药味主要为辛、苦、甘;药物主要归脾、胃、肺三经,其次是肝经;关联规则获得木香-紫苏梗、陈皮-紫苏梗、法半夏-陈皮等23个核心药对;聚类分析将药物分为3个组合,有理气除痞、祛湿化滞、清热解毒等功效。结论 劳绍贤教授治疗胃痞的核心处方为木香、紫苏梗、陈皮、法半夏、甘草、柿蒂、枳实、大腹皮;重在调畅中焦气机,脾胃同治,以理气除痞为主要治法,同时重视祛湿化滞、清热解毒类药物的应用,临床疗效显著,可供诊疗参考。     

网络环境下的病案首页质量问题与管理

目的实现医院病案首页质量管理的自动化、体系化、制度化,提高医院病案首页质量,为医院管理提供准确、及时、有效的决策依据。方法依托医院信息系统,建立相关制度,开发相关软件,实现病案首页质量管理。结果提高了医院病案首页质量,为医院管理提供了大量有效、准确的数据。结论网络环境下可以通过制度与软件相结合的方法,提高病案首页质量。