1. Application of imatinib plasma concentration monitoring in the whole process management of gastrointestinal stromal tumor patients
Linxi YANG ; Ming WANG ; Runhao XU ; Lin TU ; Chun ZHUANG ; Wenyi ZHAO ; Xinli MA ; Min LI ; Jie ZHANG ; Hui CAO
Chinese Journal of Gastrointestinal Surgery 2019;22(9):841-847
Objective:
To investigate the significance of monitoring imatinib mesylate (IM) plasma concentrations in patients with gastrointestinal stromal tumor (GIST).
Methods:
A retrospective descriptive study was carried out. Inclusion criteria: (1) patients with GIST confirmed by postoperative pathology or puncture pathology receiving maintenance therapy of IM; (2) administration of same dose of IM for at least 4 weeks (achieving steady - state plasma concentration). Patients who had severe organ dysfunction, received IM generics, or received IM simultaneously with other drugs significantly affecting IM pharmacokinetic were excluded. A total of 185 patients at the GIST Clinic of Renji Hospital, Shanghai Jiaotong University School of Medicine from August 2018 to May 2019 were enrolled, including 114 males (61.6%) and 71 females (38.4%) with a median age of 60 years old (range, 30-89 years), and 63 advanced cases. Patients receiving preoperative or postoperative adjuvant therapy were given IM 400 mg QD; patients with KIT exon 9 mutation or with disease progression during IM 400 mg QD treatment were given IM 600 mg QD. If the patient had adverse reactions such as myelosuppression during the medication, IM would be reduced or given BID per day. The peripheral venous blood was collected (22 to 24 hours after the last dose for patients who took IM QD and 2 hours before the first dose per day for those who took IM BID). IM plasma concentration was measured through high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Correlation analysis between IM plasma concentration results and clinical data was performed using linear regression analysis.
Results:
A total of 241 stable blood samples of IM plasma concentration from 185 patients were finally collected. The IM plasma concentrations were significantly different between the doses of 300 mg/d and 400 mg/d [(942.4±433.5) μg/L vs. (1340.0±500.1) μg/L,
2.Mechanism of Shengmaisan Regulating Cardiac Remodeling of Arrhythmias with Deficiency of Qi and Yin
Jingheng WEI ; Xiaolu SHI ; Wei YANG ; Cong HUANG ; Mengru SHI ; Runhao MA ; Mingjie SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):248-259
Arrhythmia is an important disease among cardiovascular diseases. Malignant arrhythmias often occur clinically and are induced by abnormal ion channels, electrical activity disorders, myocardial fibrosis, inflammation, dysfunctional mitochondrial biogenesis, mitochondrial calcium overload, out-of-balance energy metabolism, oxidative stress, sympathetic hyperactivity, and other pathological cardiac remodeling, and they are the main causes of sudden cardiac death. In traditional Chinese medicine, arrhythmias are considered to be palpitations, which are commonly caused by deficiency of Qi and Yin. It is often manifested as a deficiency of the spleen and stomach, resulting in malfunction of the Qi mechanism, followed by a particularly severe decline in cardiac function. Shengmaisan is a representative formula for nourishing Qi and Yin, consisting of Ginseng Radix et Rhizoma, Ophiopogonis Radix, and Schisandrae Chinensis Fructus. In recent years, clinical studies have shown that Shengmaisan and its additions and subtractions are commonly used in the treatment of arrhythmias. In this article, the mechanisms of the active ingredients of Shengmaisan in the electrophysiology, biochemistry, structure, autonomic nervous system, and subcellular fraction of the heart are reviewed, and the multi-target, multi-system, and integrality of Shengmaisan in the treatment of arrhythmias of Qi and Yin deficiency are described. In addition, energy metabolism disorder is tightly juxtaposed with Qi and Yin deficiency syndrome. Mitochondria, as the center of myocardial energy metabolism, play a paramount role in cardiac remodeling, indicating that Shengmaisan will be a salient part of future research to ameliorate cardiac pathologic remodeling through energy metabolism of mitochondria, so as to provide a theoretical basis for the clinical treatment of these arrhythmias.