Phytochemistry, Metabolism, and Metabolomics of Ginseng

Ginseng, as a medicinal plant, has been used for thousands of years in China, Korea, and Japan, and the study on ginseng is a hotspot in the research field as evidenced by about 7000 scientific papers in PUBMED. In recent decades, many ginseng studies focused on the metabolism and metabolomics of ginseng or its active ingredients using modern bioanalytical technologies. To date, more than 200 ginsenosides and non-saponin constituents have been isolated and identified. In the past decades, rapid development of analytical technologies has facilitated the advancement of ginseng research in many ways. In this review, we focus on the advances of ginseng research in chemistry, pharmacology, and metabolomics. We also provide the comments on the significance as well as challenges of metabolomics-based ginseng studies.     

Charcoal-based hemodiabsorption liver support for episodic type C hepatic encephalopathy

OBJECTIVES: Episodic (acute) type C hepatic encephalopathy (AHE) fails to respond to 5 days of medical therapy in 10-30% of patients and carries a 10-30% mortality rate. We prospectively studied extracorporeal liver support for AHE failing to respond to medical therapy to assess its safety and efficacy and the role of anticoagulation. METHODS: A series of patients with cirrhosis and AHE failing to respond to at least 24 h of medical therapy underwent a maximum of three 6-h charcoal-based hemodiabsorption (Liver Dialysis Unit) treatments. A standard anticoagulation protocol, with heparin dosing based on activated clotting time (ACT) determinations, heparin dose-response curve, and target ACT of 275-300 s, was developed. Therapy was terminated if patients met a predetermined clinical response, deteriorated, or underwent transplantation. RESULTS: Eighteen patients with grade 2-4 AHE despite 5.9 +/- 3.9 days of medical therapy underwent a mean of 1.6 treatments. In 2.6 +/- 1.9 days, 16 patients (88.9%) improved to less than grade 2 HE or achieved at least a 50% hepatic encephalopathy index (HEI) reduction. Median mental status (grade 2 vs 1, p < 0.05) and HEI (0.634 +/- 0.194 vs 0.363 +/- 0.263, p < 0.005) improved significantly. Survival was 94.4% and 72.2% at 5 and 30 days, respectively. Use of our developed anticoagulation protocol resulted in less platelet (14.2% +/- 2.8% vs 32.5% +/- 5.8%, p < 0.005) and fibrinogen consumption (12.1% +/- 3.5% vs 43.3% +/- 8.6%, p < 0.0005) and blood product use (6.2 +/- 1.8 vs 19.0 +/- 5.6 units, p < 0.05) compared with treatments according to manufacturer's guidelines. CONCLUSIONS: Charcoal-based hemodiabsorption treatments in which a standardized anticoagulation protocol is used is safe and effective treatment for AHE not responding to standard medical therapy.     

脑心通胶囊对冠心病无症状心肌缺血病人血管内皮依赖性舒张功能的影响

目的探讨脑心通胶囊治疗冠心病无症状心肌缺血(SMI)的疗效及其对血管内皮依赖性舒张功能的影响。方法随机将68例冠心病SMI病人分为两组,治疗组35例在常规药物治疗基础上加用脑心通胶囊治疗,对照组33例仅用常规药物治疗。治疗前后进行动态心电图及彩色多普勒超声检测,对缺血及血管内皮依赖性舒张功能的相关指标作对比观察。结果两组治疗12周后S,T段压低伴有症状的次数及其持续时间与无症状的ST段压低及其持续时间均有明显减少及缩短,与治疗前比较有统计学意义(P<0.05或P<0.01),治疗后两组比较也有统计学意义(P<0.05)。治疗组治疗后血管内皮依赖性舒张功能指标明显改善(P<0.01),与对照组比较差异亦有统计学意义(P<0.01)。用药期间病人无严重不良反应。结论脑心通胶囊对冠心病无症状心肌缺血有显著疗效,且能改善血管内皮依赖性舒张功能。     

A randomised phase II trial of selumetinib vs selumetinib plus temsirolimus for soft-tissue sarcomas

Background:

The MEK inhibitor, selumetinib, suppresses soft-tissue sarcoma (STS) cell proliferation in vitro. Mammalian target of rapamycin inhibitors possess modest activity against STS; however, resistance develops via MAPK pathway feedback activation. The combination of selumetinib and temsirolimus synergistically inhibits STS cell line growth. Therefore, a randomized phase II trial of selumetinib vs selumetinib plus temsirolimus was conducted.

Methods:

Seventy-one adults with advanced STS who received ⩽2 prior chemotherapeutics were randomized to selumetinib 75 mg p.o. bid and allowed to crossover upon progression, or to selumetinib 50 mg p.o. bid plus temsirolimus 20 mg i.v. weekly, with primary endpoint of progression-free survival (PFS).

Results:

There was no difference in PFS between the two arms for the overall cohort (median 1.9 vs 2.1 months); an improved median PFS was observed in the combination arm (N=11) over single agent (N=10) in the prespecified leiomyosarcoma stratum (median 3.7 vs 1.8 months; P=0.01). Four-month PFS rate was 50% (95% confidence interval 0.19–0.81) with the combination vs 0% with selumetinib alone in the leiomyosarcoma cohort. Most common grade 3/4 adverse events with the combination were mucositis (29%), lymphopenia (26%), neutropenia and anaemia (20% each).

Conclusions:

While single-agent selumetinib has no significant activity in STS, the combination may be active for leiomyosarcomas.     

子宫内膜癌单通道和六通道柱状施源器三维近距离照射的剂量学比较

目的 比较单通道和六通道柱状施源器2D、3D治疗计划靶区和正常组织照射剂量,评估三维近距离治疗在子宫内膜癌术后阴道内照射中的应用优势。方法 早期子宫内膜癌10例,分别置入六通道和单通道柱状施源器,CT模拟定位扫描后做治疗计划。CTV定义为阴道上段3 cm,黏膜下5 mm区域,处方剂量为5 Gy/次,共6次。分别制定不同施源器2D和3D治疗计划。比较两种施源器2D与3D计划CTV和OAR的剂量。结果 两种施源器2D、3D治疗计划均能很好满足CTV剂量要求。使用单通道施源器时3D计划可显著降低直肠D_{0.1 cm³}、D_{1.0 cm³}、D_{2.0 cm³}约18.2%、12.4%和10.7%。使用六通道施源器时,3D计划可显著降低直肠D_{0.1 cm³}、D_{1.0 cm³}、D_{2.0 cm³}和D_mean约36.6%、24.8%、20.4%和6.1%,并降低了膀胱和尿道D_mean。与单通道施源器3D计划相比,六通道施源器3D计划进一步降低了直肠、膀胱和小肠的照射剂量。结论 使用单通道或六通道柱状施源器进行阴道内照射时,2D和3D治疗计划均取得了很好的靶区剂量分布。3D治疗计划与2D治疗计划相比,能降低以直肠为主的OAR受量,六通道施源器3D计划进一步降低了直肠照射剂量。     

Multiple oncogenic mutations related to targeted therapy in nasopharyngeal carcinoma

Introduction:An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related oncogenic mutations have not been fully evalu...     

ITP患儿血小板内cAMP的研究

本文用放免法测定了38例正常儿及47例 ITP 患儿血小板内 cAMP 值。发现无论急、慢性患儿血小板内 cAMP 值均显著增高,其增高与血小板功能呈负相关,与血小板计数无相关性。急性患儿 PAIgG 增高,血小板内 cAMP 亦增高,二者之间呈正相关,而慢性患儿则无此相关性。并对 cAMP 的增高与 ITP 的发病机制进行了阐述。     

慢病毒介导生长分化因子15基因沉默增强胶质瘤U373细胞的化疗耐药性

目的:探讨慢病毒介导的生长分化因子15(growth differentiation factor 15,GDF15)基因低表达对胶质瘤U373细胞对化疗药物替尼泊苷(teniposide,VM-26)和顺铂(cisplatin,DDP)耐药性的影响及其可能的机制。方法:将靶向GDF15的GDF15-RNAi克隆入慢病毒载体GV248,构建shRNA慢病毒LV-GDF15-RNAi,用无关序列构建阴性对照慢病毒LV-RNAi,分别稳定转染U373细胞,Western blotting检测转染对细胞内GDF15表达的影响。用梯度质量浓度的VM-26(0.1、0.5、2.5和12.5μg/ml)和DDP(0.08、0.4、2和10μg/ml)处理LV-GDF15-RNAi组和LV-RNAi组细胞48 h,MTT法、Hoechst/PI双染检测LVGDF15-RNAi转染对U373细胞VM-26、DDP耐药性的影响,Western blotting检测LV-GDF15-RNAi转染对U373细胞凋亡相关蛋白Bcl-2、Bcl-x L、P53和Caspase-3表达的影响。结果:成功构建稳定低表达GDF15的U373细胞系,LV-GDF15-RNAi组细胞内GDF15表达较LV-RNAi组和野生型U373细胞显著降低(0.013±0.001 vs 0.622±0.068、0.601±0.004,均P<0.01)。VM-26和DDP在最低浓度时,LV-GDF15-RNAi组细胞存活率即显著高于LV-RNAi组[VM-26 0.1μg/ml:(91.84±2.64)%vs(80.71±2.66)%,P<0.01;DDP 0.08μg/ml:(102.35±6.79)%vs(85.10±3.69)%,P<0.01],随药物浓度升高差异更加显著。相同浓度的VM-26或DDP处理下,LV-GDF15-RNAi组细胞凋亡数均少于LV-RNAi组;同时,LV-GDF15-RNAi组的Bcl-2和Bcl-x L的表达量比LV-RNAi组显著增多(P<0.05或P<0.01),Caspase-3和P53的表达量显著下降(P<0.05或P<0.01)。结论:下调胶质瘤U373细胞中GDF15水平能够增强细胞对VM-26和DDP的耐药性,其机制可能与GDF15调控Bcl-2、Bcl-x L、P53和Caspase-3的表达有关。