刺南蛇藤倍半萜的研究

从刺南蛇藤(Celastrus flagelaris Rupr.)种子油中分离到八个β-二氢沉香呋喃倍半萜,经红外、紫外、质谱及核磁共振谱确定它们的结构是1α-乙酰氧基-2α,9β-二肉桂酰氧基-β-二氢沉香呋喃(1),1α,6β,13-三乙酰氧基-9β-苯甲酰氧基-β-二氢沉香呋喃-(2),triptogelinG-1(3),1α,6β-二乙酰氧基-9β-苯甲酰氧基-β-二氢沉香呋喃(4),triptogelinF-2(5),1α,2α-二乙酰氧基-9β-肉桂酰氧基-β-二氢沉香呋喃(6),celaforlinB-3(7),1α,6β-二乙酰氧基-8α-肉桂酰氧基-9α-苯酰氧基-β-二氢沉香呋喃(8)。其中1是新化合物,命名为celastrine B。     

The combined use of steroids and immune checkpoint inhibitors in brain metastasis patients: a systematic review and meta-analysis

BackgroundImmune checkpoint inhibitors (ICI) have been a breakthrough for selected cancer patients, including those with brain metastases (BMs). Likewise, steroids have been an integral component of symptomatic management of BM patients. However, clinical evidence on the interaction between ICI and steroids in BM patients is conflicting and has not adequately been summarized thus far. Hence, the aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI.MethodsA systematic literature search was performed. Pooled effect estimates were calculated using random-effects models across included studies.ResultsAfter screening 1145 abstracts, 15 observational studies were included. Fourteen studies reported sufficient data for meta-analysis, comprising 1102 BM patients of which 32.1% received steroids. In the steroid group, median OS ranged from 2.9 to 10.2 months. In the nonsteroid group, median OS ranged from 4.9 to 25.1 months. Pooled results demonstrated significantly worse OS (HR = 1.84, 95% CI 1.22-2.77) and systemic progression-free survival (PFS; HR = 2.00, 95% CI 1.37-2.91) in the steroid group. Stratified analysis showed a consistent effect across the melanoma subgroup; not in the lung cancer subgroup. No significant association was shown between steroid use and intracranial PFS (HR = 1.31, 95% CI 0.42-4.07).ConclusionsAdministration of steroids was associated with significantly worse OS and PFS in BM patients receiving ICI. Further research on dose, timing, and duration of steroids is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.     

Tumour control by whole brain irradiation of anti-VEGF-treated mice bearing intracerebral glioma

Aim of the studyTumour angiogenesis and invasion are key features of glioblastoma multiforme (GBM). Angiogenesis inhibitors increase progression-free survival (PFS) of recurrent GBM patients. VEGF inhibition controls the bulk tumour growth by inhibition of angiogenesis, but does not inhibit the invasive tumour component. We investigated if invasive tumour growth can be controlled by combining anti-VEGF treatment with irradiation of tumour plus surrounding brain in an orthotopic murine model for GBM.Methods and materialsGBM cell line U251-NG2 was inoculated through a guide screw in the right frontal lobe of 53 athymic nude mice. Pegaptanib (a slow-releasing aptamer against VEGF) was injected in the tumour bed either or not followed by irradiation treatment with implanted I-125 seeds. Pegaptanib and/or irradiation were compared with sham-treated controls, resulting in four groups of 10–15 mice each. After 6 weeks of treatment, histological analysis was performed on all brains.ResultsVEGF inhibition by locally deposited pegaptanib decreased tumour blood vessel density, and increased tumour hypoxia. Pegaptanib treatment still allowed the formation of tumour satellites. Irradiation decreased tumour size and suppressed formation of satellites. Combined pegaptanib plus irradiation further increased PFS. Tumour size directly correlated with PFS.Concluding statementThe anti-tumour effects of local VEGF inhibition are partially circumvented by the formation of invasive tumour satellites. Additional irradiation is effective in slowing down proliferation of these invasive tumour components.     

高效液相色谱法同时测定五加中剌五加苷B、苷E的含量

目的测定甘肃产五加中剌五加苷B、苷E的含量。方法高效液相色谱法,ODSKromasal柱。水乙晴(955)为流动相,检测波长222nm,柱温度25℃。结果本文可同时测定剌五加苷B、苷E的含量。剌五加苷B、苷E分别在0.064～0.320μg/ml;0.074～0.370μg/ml范围内峰面积与浓度呈线性关系,平均回收率分别为102.5%,RSD=4.2%,95.5%,RSD=4.6%。结论剌五加苷B、苷E在红毛五加中含量最高;茎皮中含量最高;剌五加苷E的含量高于苷B。     

The Impact of Migraine on Health Status

Problems.-What is the effect of migraine on health status, defined as the patient's physical, psychological, and social functioning? And, suppose that the health status of migraine sufferers appears to be impaired, to what extent is this a consequence of migraine-associated comorbidity rather than of migraine itself? Methods.-A group of 846 migraineurs, selected from the general population following IHS criteria, and a control group were surveyed with the Medical Outcomes Study 36-item Short-Form Health Survey, Nottingham Health Profile, EuroQol instrument, end the COOP/WONCA charts. Questions on demographic characteristics and comorbidity were included. Results.-The health status of migraineurs appeared to be significantly impaired in comparison to the control group. Because statistical significance is distinct from relevance, effect size estimators were employed. Although the direction of the differences indicated consistently a worse health status of the migraineurs, regardless of the instrument used, the sizes of the differences were small to medium. Self-reported comorbidity, especially depression, was more prevalent in the migraine group. However, this offered only a partial explanation for the impaired health status of the migraine group. Conclusions.-Migraine has an independent moderately deteriorating effect on the daily functioning of individuals.     

Dopamine receptor availability in Tourette''s syndrome

A large body of evidence suggests that abnormal dopaminergic activity is present in Gilles de la Tourette Syndrome (GTS). To investigate whether dopamine dysregulation involving the D₂/D₃ receptor occurs in GTS, we performed single slice dynamic single photon emission computed tomography (SPECT) with ¹²³iodo-6-methoxybenzamide (¹²³I-IBZM) in 15 GTS patients (eight unmedicated) and six healthy volunteers. After intravenous administration of 5 mCi (185 MBq) of ¹²³I-IBZM, dynamic SPECT (5 minutes per slice) studies were performed at the level of the basal ganglia for 55 minutes. The mean activity per pixel in the basal ganglia was compared with the mean activity per pixel in the visual cortex. Unmedicated GTS patients showed no differences from control subjects. However, GTS patients taking D₂ blocking medications had significantly decreased ¹²³IIBZM binding compared with control subjects in both the right and left basal ganglia. Thus, D₂/D₃ receptor availability, as measured by ¹²³I-IBZM SPECT, is not abnormal in GTS.     

人白血病HL60细胞的分化状态对细胞凋亡的影响

用细胞培养和流式细胞术等方法,研究人白血病HL60细胞诱导分化后,对三尖杉酯碱(Har)和喜树碱(Cam)诱导细胞凋亡的影响。结果表明,12-豆蔻酰及13-乙酸佛波酯以16nmol·L^-1浓度处理HL60细胞24h,细胞向单核/巨噬细胞方向分化,阻断于G_{1期;分化细胞抗Har和Cam诱导的细胞凋亡,但其c-myc基因的表达无变化。1.4%二甲基亚砜处理HL60细胞48h,细胞向粒细胞方向分化,阻断于G1期;分化细胞抗Cam,而不抗Har诱导的细胞凋亡;分化细胞的c-myc基因表达明显下降。结果提示,人白血病HL60细胞的分化状态,明显影响三尖杉酯碱和喜树碱诱导的细胞凋亡,但可能与c-myc基因的表达变化无关。}