Initial dosage optimization of tacrolimus in Chinese pediatric patients undergoing kidney transplantation based on population pharmacokinetics and pharmacogenetics

ABSTRACT

Background

The purpose of our research was to recommend the initial tacrolimus dosage for Chinese pediatric patients undergoing kidney transplantation based on population pharmacokinetics and pharmacogenetics.     

加味金宁方抑制磨玻璃样早期肺癌术后复发的临床评价

  目的：观察加味金宁方对磨玻璃样早期肺癌术后复发的抑制作用。  方法：将72例磨玻璃样早期肺癌术后患者随机分为治疗组和对照组,每组36例。治疗组服用加味金宁方,对照组服用1/20剂量加味金宁方。两组均连续服药1年或至病情进展,观察实体瘤疗效、免疫疗效,比较中医证候积分的变化情况。  结果：①试验过程中治疗组、对照组各脱落3例,最终有效完成试验的病例66例,治疗组、对照组各33例。②实体瘤疗效:在术后1年内,治疗组、对照组的疾病控制率分别为93.94%、72.73%；治疗组实体瘤疗效优于对照组(P<0.05)。③免疫疗效:术后3个月治疗组、对照组有效率分别为75.76%、69.70%,两组免疫疗效差异无统计学意义(P>0.05)；术后6个月、术后9个月、术后12个月两组免疫疗效比较,治疗组优于对照组(P<0.05)。④治疗后,两组中医证候积分均呈持续下降趋势,与本组前一观察时点比较,差异有统计学意义(P<0.05)；术后6个月、术后9个月、术后12个月组间比较,治疗组中医证候积分低于对照组(P<0.05)。  结论：加味金宁方对磨玻璃样早期肺癌术后复发具有一定的抑制作用,且有助于促进机体免疫功能的恢复,并改善中医证候,值得临床推广应用。     

缓解视疲劳功能中药复方保健产品配方规律及特点分析

目的通过检索特殊食品信息查询平台公布的具有缓解视疲劳功能的保健食品信息资料,以及药智数据网的中成药处方数据库中眼科中成药中有保健功能的产品信息资料,为具有缓解视疲劳功能的保健产品的组方与产品开发提供依据与参考。方法运用Microsoft Excel2016软件及中医传承辅助平台对检得的产品信息进行统计,分析其配方特点。结果共收集到141个具有缓解视疲劳功能的保健食品,其中64个(45.4%)保健食品配方中含有中药类原料。使用频次≥5的中药原料有6味,累计使用145次(72%),由高到低分别是菊花、枸杞子、决明子、桑椹、熟地黄、茯苓。通过无监督的熵层次聚类得到3个新处方。非中药原料在缓解视疲劳功能的保健食品中应用较为普遍,含有外来天然植物资源的60个产品,含叶黄素及维生素类的17个。统计眼科中成药中有保健功能的产品可知,使用频次≥4的中药原料有7味,累计使用32次(29%),由高到低分别是枸杞子、决明子、菟丝子、熟地黄、菊花、五味子、车前子。通过无监督的熵层次聚类得到1个新处方。结论保健食品在中药原料的选择上与中医药理论治疗视疲劳的原则基本契合,即滋补肝肾、平肝明目。但二者在中药原料选择范围、原料配伍、剂型种类等方面有所不同。此外,还在辨证保健理论指导下,尝试探讨应用文献数据处理统计方法筛选新配方、开发新产品,为中药复方保健产品的研发开辟了新思路、新方法。     

Choosing wisely in the ED: The diagnostic cascade of needless medical testing in a two-level study

BackgroundThe diagnostic cascade in the emergency department (ED) has not been fully elucidated.AimTo inspect whether the usage of consulting medicine and imaging contributes to hospital outcomes. We also propose a theoretical model for better understanding the diagnostic cascade of needless medical testing.MethodsA two-level study was conducted. The first local phase was a retrospective archive study that was conducted between 2014 and 2017 in a tertiary hospital. We extracted the number of requested imaging and consultations for each patient, and main time lags were calculated. The second-phase (January–April 2018) was conducted on a national level. We examined 22 hospitals with the emphasis on five hospital outcomes: recurrent ED visits (within 24 h), median waiting time at the ED, rate of early discharge at the same day and day after and percentage of patients spending >4 h in the ED.ResultsA 5% upsurge in CT scans was observed (p = .032), and a significant increase was found in the number of consultations (14%, p = .002). On a national level, a linear regression model found that the proportion of patients discharged from the hospital on the same day and on the day after and the proportion of patients staying in the ED > 4 h predict ED recurrence visits within 24 h (p = .025; R² = 46.3%).ConclusionsUpsurge in resource usage in the ED leads to a diagnostic cascade of health consumption. Further study is necessary to examine the proposed model in a global scale.     

针对射程不确定性的质子调强放疗鲁棒优化方法

目的 因治疗精度高、副作用小,质子调强放疗(IMPT)成为放疗领域的研究热点,但其精度对射程变化非常敏感。本研究提出一种针对射程不确定性的IMPT鲁棒优化方法用于减小射程偏差对放疗计划的影响。方法 首先建立鲁棒优化模型,目标函数采用二次型函数表达式,其中包含3种射程:射程增加、射程正常、射程缩短;每种射程对应的器官剂量贡献矩阵采用质子笔形束算法计算得到。对射程偏差进行离散化,每个射程的发生概率基于高斯分布函数得到。最后采用共轭梯度法优化出最优解,最优解使得靶区和危及器官实际剂量分布在射程偏差内尽量达到期望剂量。结果 采用AAPM TG-119号报告的3套模拟例题测试本研究方法的有效性:鼻咽癌病例、前列腺病例和“C”型病例。与常规IMPT优化结果对比,发现该方法对射程不确定性的敏感性更低。射程发生偏差时,鼻咽癌病例和前列腺病例的靶区和危及器官基本达到期望剂量,“C”型病例的靶区高剂量覆盖率和危及器官保护都有了提高。结论 针对射程不确定性,该方法可得到更高的靶区覆盖率,同时降低危及器官剂量。     

基于响应面法优选美洲大蠊口腔原位温敏凝胶的制备研究

目的制备美洲大蠊Periplaneta americana口腔原位温敏凝胶。方法采用自由基聚合法首次以N-异丙基丙烯酰胺(NNIPAM)和甲基丙烯酸羟丙酯(HPMA)合成聚(N-异丙基丙烯酰胺-甲基丙烯酸羟丙酯)[P(NNIPAM-HPMA)]作为温敏材料;通过冷溶法制备美洲大蠊口腔原位温敏凝胶,采用Box-Behnken设计响应面法,以溶蚀时间、胶凝时间为评价指标,在固定美洲大蠊提取物用量基础上,对羟丙基甲基纤维素(HPMC)、聚乙烯吡咯烷酮(PVP K30)、P(NNIPAM-HPMA)的用量进行优选。结果通过原位聚合法合成了P(NNIPAM-HPMA)温敏材料;并用响应面法优选了可用于口腔的美洲大蠊原位温敏凝胶的处方,优选的处方为美洲大蠊提取物10%、HPMC 3.0%、PVP K30 9.5%、P(NNIPAM-HPMA) 10.0%,其溶蚀时间为2 h,胶凝时间8～9 s。结论优选得到美洲大蠊口腔原位温敏凝胶,为美洲大蠊提取物的口腔原位局部的临床应用奠定了科学依据。     

Clinical observation on the effect of Chinese medicine-“TCM formula” intervention on recurrence and metastasis of triple negative breast cancer

ObjectiveThis study used a prospective cohort study to observe the effect of triple-negative breast cancer on the 2-year disease-free survival rate with or without “TCM formula”.MethodsFrom November 1 st, 2016, the first patient was enrolled in the cohort study. A total of 356 patients were enrolled on January 30, 2019. Among them, 154 cases were followed up for 2 years. During the follow-up, there were 6 cases of shedding, so 6 cases were affected. A total of 148 cases were included in the analysis, including 73 in the exposed group and 75 in the non-exposed group. The exposed group was given “TCM formula” on the basis of standardized treatment, and the non-exposed group was treated with simple triple-negative breast cancer. The two groups visited each of the three months. The interview included safety examination (hematology and imaging). The endpoint was the difference in 2-year invasive disease-free survival between the exposed and non-exposed groups and the safety of the “TCM formula”.ResultsThere were 6 cases of shedding during the experiment and the shedding rate was 3.9 %. The 2-year rate of invasive disease-free survival in the exposed team was 88.7 % and the non-exposed group was 82.5 %. Logistic multivariate regression analysis predicted that “TCM formula” could reduce the disease-related recurrence and metastasis rate by 11 % (OR = 0.89, 95 % CI 0.37−0.956, P＜0.05). Through K–M survival analysis, TNBC patients with age ≤35 years and regional lymph node stage N1 may be the benefit group of “TCM formula”(P＜0.05). During the study, the incidence of total adverse events was 8.2 % in the exposed group, mainly manifested as stomach discomfort, diarrhea, and hepatocyte damage.Conclusion1. In the exposed group, the two-year rate of invasive disease-free survival increased by 6.2 % compared with the non-exposed group(P＞0.05). 2. According to K–M survival analysis, TNBC patients with age ≤35 years and regional lymph node metastasis to N1 may be potential beneficiaries of “TCM formula”. 3. “TCM Formula” is safe and tolerable to most patients.     

复肝丸调控miR-424表达抑制肝窦内皮细胞血管新生的体外研究

目的观察复肝丸调控miR-424表达以抑制肝窦内皮细胞血管新生的作用及其机制。方法以不同剂量(0～2 000 mg/L)的复肝丸与人肝窦内皮细胞(HHSEC)共孵育,CCK8法检测复肝丸对细胞活力的影响,分析复肝丸对细胞无毒性作用的剂量范围,并以此作为后续药效及机制评价的剂量。以CoCl_2诱导HHSEC血管新生模型,分为正常组、模型组、miR-424抑制剂组及复肝丸组,除正常组外,其余各组以CoCl_2诱导细胞血管新生,miR-424抑制剂组及复肝丸组分别以miR-424抑制剂及复肝丸(200 mg/L)与细胞共孵育24 h。采用CCK8法检测细胞活力与增殖情况;Transwell观察细胞迁移变化情况;Matrigel管腔生成实验评价细胞管腔形成情况;定量RT-PCR检测miR-424、HIF-1α、vWF、CD31基因表达;Western blot法检测HIF-1α、vWF、CD31蛋白表达。结果复肝丸剂量小于400 mg/L对HHSCE无明显细胞毒性。与正常组比较,200μmol/L CoCl_2可诱导肝窦内皮细胞缺氧损伤模型,且模型组miR-424、HIF-1α表达增加,细胞迁移和管腔生成增多,vWF、CD31表达增加(P0.01);与模型组比较,miR-424抑制剂与200 mg/L复肝丸干预后,miR-424与HIF-1α表达均不同程度降低,细胞迁移和管腔生成受抑制,vWF、CD31表达降低(P0.01);且复肝丸组综合疗效与miR-424抑制剂相当。结论复肝丸具有良好的抑制肝窦内皮细胞血管新生的作用,其作用机制与抑制miR-424表达相关。