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.     

Quantile regression and empirical likelihood for the analysis of longitudinal data with monotone missing responses due to dropout,with applications to quality of life measurements from clinical trials

The analysis of quality of life (QoL) data can be challenging due to the skewness of responses and the presence of missing data. In this paper, we propose a new weighted quantile regression method for estimating the conditional quantiles of QoL data with responses missing at random. The proposed method makes use of the correlation information within the same subject from an auxiliary mean regression model to enhance the estimation efficiency and takes into account of missing data mechanism. The asymptotic properties of the proposed estimator have been studied and simulations are also conducted to evaluate the performance of the proposed estimator. The proposed method has also been applied to the analysis of the QoL data from a clinical trial on early breast cancer, which motivated this study.     

中药复方配伍的研究方法及其进展

中药复方是由2味或2味以上中药遵循中医理论组合而成的方剂。多味中药在合适的剂量配比之下,协同发挥作用,实现中医的整体调节治疗。研究中药复方的配伍对推动中药现代化发展、新药开发以及临床应用有着重要意义。近年来,研究者们在传统的"七情和合"与"君臣佐使"的基础上,运用新技术和新方法对中药复方的成分、药效活性和药代动力学性质等进行了研究,从不同角度探讨了中药复方配伍的科学内涵。同时,多种数理方法和模型的建立、网络药理学和数据挖掘方法的发展与应用,也对中药复方配伍研究提供了很大帮助。研究方法的发展虽促进了中药复方配伍的科学研究,但还需进一步建立适合中药复方配伍复杂关系的研究方法,以阐明中药复方及其成分/组分配伍的内在规律,进而构建新的现代中药复方,这也是目前中药复方配伍研究的重点任务。     

In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.     

高海拔地区精神分裂症患考临床特征分析

目的:了解高海拔环境对精神分裂症的影响。方法:对106例高海拔地区精神分裂症患者(高海拔组)的临床特征、疗效、药物副作用进行调查,与同期106例平原精神分裂症患者(平原组)对照。结果:高海拔组临床症状以幻觉、疑病妄想、夸大妄想、紧张冲动行为及焦虑、抑郁等精神症状出现频率较高,而对照组以被害妄想、情感淡漠等精神症状出现频率较高(P<0.01或P<0.05);入院时高海拔组总体病情较重(P<0.01);两组间疗效无显著性差异;高海拔组药物不良反应多于平原组。结论:高海拔地区精神分裂症患者临床特征、总体病情严重程度、药物不良反应与平原地区有一定区别,可能与高海拔环境有关。     

硫化氢及一氧化氦气体信号分子在高原高血压发病中的作用

目的 探讨气体信号分子硫化氢（H2S）及一氧化氮（NO）在高原高血压的病理生理意义。方法 平原体检正常者进入海拔5000m高原（1～3）月期间，在高原暴露时间、劳动强度及生活条件相同的施工群体中随机抽样127人。依血压变化将其分为高原高血压（Ⅰ～Ⅲ级）组78人（进一步分为收缩期高原高血压组与舒张期高原高血压组），高原正常血压组49人，采取肘静脉血，采用敏感硫电极法测定其H2S浓度，Griess法测定血清NO含量。结果 高原高血压组、收缩期高原高血压组、舒张期高原高血压组的血清H2S与NO平均含量均显著增加，分别比正常血压组高34．5％，36．9％，31.7％（均P〈0．001）与28．4％，33．1％，39．7％，（均P〈0．05），尤以H2S更为突出；随着血压分级程度的升高H2S与NO血清含量相应增高，也以H2S更显著（R^2=0．918）；H2S与NO、舒张压间均有密切正相关关系及良好的拟和优度、与氧饱和度呈显著的负相关与拟和优度（R^2=0．374，P=0．001）。结论 H2S与NO的代谢失常可能参与了高原高血压发病过程。     

高压氧预适应对大鼠高原颅脑损伤的作用研究

目的探讨高压氧（HBO）预适应对高原颅脑损伤（TBI）的神经保护作用。方法将78只SD大鼠随机分为平原组、高原组和高压氧预适应组，各组按Feeney自由落体撞击法制作TBI模型，并通过低压氧舱模拟高原环境。采用Longa评分法进行神经功能缺损评分，Moor DRT4激光多普勒血流监测仪和LICOX CMP组织氧分压监测仪分别监测伤区局部脑血流（rCBF）和局部脑组织氧分压（PbtiO2）变化，利用光镜观察伤区脑组织的病理学改变。结果伤后24h高原组较平原组神经功能缺损评分上升。rCBF和PbtiO2下降，病理损伤加重；高压氧预适应组较高原组神经功能缺损评分下降（P〈0.05），rCBF和PbtiO2升高（均为P〈0.05）病理损伤减轻。结论高压氧预适应可诱导对高原颅脑损伤的神经保护作用改善神经功能。     

MRI技术对高原人群颅脑脱髓鞘疾病回顾性研究

目的研究高原地区,脱髓鞘疾病与中老年人疾病等因素的关系。方法对我院所有接受过磁共振头部扫描的病人进行评估,确诊出40位脱髓鞘疾病患者,并对大脑7个部位的脱髓鞘疾病按严重性分4级打分,统计临床数据,最后运用统计学方法分析其相关性。结果在40例患者中,出现在大脑半球、放射冠、半卵圆中心和脑室前后角的脑白质损伤频率最多,分别占总量的50%、67.5%、77.5%和87.5%。脑白质损伤患者的平均年龄为47.1岁,这比世界其他地区都有明显的提前。男性患者将近是女性患者的3倍(29∶11)。年龄、慢性高原红细胞增多症、收缩压、脑梗塞与脑白质损伤正相关(P<0.05)。结论对于高海拔地区,有效控制高原心血管疾病的发生对于减少颅脑脱髓鞘疾病的发生具有重要意义。     

血管内皮生长因子在高原脑水肿形成中作用的实验研究

目的:探讨血管内皮生长因子(VEGF)在高原脑水肿形成中的作用。方法:建立大鼠模拟高原模型,应用脑干湿重比率法定量脑水肿情况、应用荧光素钠透过率测定BBB通透性、应用实时荧光定量RT-PCR法检测脑组织VEGF mRNA含量以及应用蛋白印迹法半定量脑组织VEGF含量。结果:大鼠在高原24 h后脑组织含水率明显增高(P<0.05),荧光素钠透过率显著增加(P<0.01);VEGF mRNA转录及其表达显著增高(P<0.001)。结论:VEGF表达在高原脑水肿形成中起重要作用。