多靶点酪氨酸激酶抑制剂治疗恶性肿瘤的群体药动学研究进展

多靶点酪氨酸激酶抑制剂是临床常用的抗肿瘤药物,其通过抑制细胞信号转导,从而促进肿瘤细胞凋亡,具有选择性高,副作用少的特点。目前在非小细胞肺癌、转移性肾癌、甲状腺癌及血液肿瘤等恶性肿瘤的治疗中应用广泛。但该类药物在临床疗效和药动学特征等方面受多种因素的影响,存在较大的个体差异。近年来,群体药动学研究发展迅速,广泛应用于多种药物的研究。笔者综述了阿昔替尼、伊马替尼、厄洛替尼和舒尼替尼在肿瘤患者及健康人群中的药动学特征及影响因素,进而对其群体药动学研究进展进行总结,分析了其在不同瘤种中的药动学特点及其相关协变量。结果表明,人口统计学因素、基因多态性、血生化指标、合并用药和肝肾功能是影响其在体内代谢的重要因素。试验设计和模型构建等因素可能是导致研究结果产生差异的重要原因。本文为临床制定合理、安全的个体化给药方案制定提供理论参考。     

Segmental branches emanating from saphenous nerve morphing into sympathetic trunks for innervation of saphenous artery and its clinical implication for arterial sympathectomy

Sympathectomy of arteries has been adopted for the treatment of peripheral arterial disease and Raynaud''s disease. However, the exact route for sympathetic axons to reach peripheral arteries awaits further investigation that could pave the way for development of new surgical strategies. In this study, saphenous neurovascular bundles from 10 neonatal Sprague‐Dawley rats first were harvested for whole‐mount immunostaining to show sympathetic innervation pattern of the artery. Secondly, 40 Sprague‐Dawley male rats weighing 350 to 400 g were assigned to five groups, receiving either sham, perivascular sympathectomy, nerve‐artery separation, nerve transection in the saphenous neurovascular bundle, or lumbar sympathectomy surgery that removes the lumbar sympathetic trunks. Immediately after surgery, the arterial perfusion and diameter were measured using laser speckling contrast imaging, and 1 week later the saphenous neurovascular bundles were harvested for immunostaining using antibodies against TH, neuron‐specific β‐tubulin (Tuj 1), and α‐SMA to show the presence or absence of the TH‐immuopositive staining in the adventitia. The differences among the five groups were determined using one‐way analysis of variance (ANOVA). We found that an average of 2.8 ± 0.8 branches with a diameter of 4.8 ± 1.2 μm derived from the saphenous nerve that morphed into a primary and a secondary sympathetic trunk for innervation of the saphenous artery. Nerve‐artery separation, nerve transection, and lumbar sympathectomy could eradicate TH‐immunopositive staining of the artery, resulting, respectively, in a 12%, 36%, and 59% increase in diameter (P < .05), and a 52%, 63%, and 201% increase in perfusion compared with sham surgery (P < .01). In contrast, perivascular sympathectomy did not have a significant impact on the TH‐immunopositive staining, the diameter, and perfusion of the distal part of the artery (P > .05). We conclude that the sympathetic innervation of an artery derives from segmental branches given off from its accompanying nerve. Nerve‐artery disconnection is a theoretic option in sympathectomy of an artery.     

大剂量孕激素在年轻患者早期子宫内膜癌治疗中的应用

目的 探讨年轻女性子宫内膜癌的诊断、治疗及预后的特点.方法 口服大剂量孕激素,根据子宫内膜逆转情况调节药物用量.结果 子宫内膜癌逆转,并IVF-ET受孕成功,分娩1个正常女婴.结论 年轻妇女子宫内膜癌多与月经不调、不孕不育、多囊卵巢综合征等高危因素有关;以手术治疗为主,分化好病理分期Ⅰ期、有迫切生育要求者,可在严密观察下行药物保守治疗并助孕.     

曾被误诊的麻痹性痴呆23例分析

目的:研究麻痹性痴呆的诊断与治疗。方法:对曾被误诊的23例麻痹性痴呆,使用简明精神病评定量表(BPRS)及简易精神状态检查(MMSE)评定。并予驱梅毒及抗精神病药治疗。结果:驱梅毒治疗后可显著提高疗效。结论:麻痹性痴呆应及早正确诊断,作驱梅毒及抗精神病治疗。     

Inhibition of In Vitro Infection of Hepatitis B Virus by Human Breastmilk

Despite the presence of hepatitis B virus (HBV) in the human breastmilk of mothers infected with HBV, it has been shown that breastfeeding does not increase the risk of mother-to-child transmission (MTCT) of HBV. We tested the hypothesis that human breastmilk may contain active components that bind to HBV and inhibit the infectivity of HBV. The results show that human whey significantly inhibited the binding of the hepatitis B surface antigen (HBsAg) to its antibodies in competitive inhibition immunoassays. The far-western blotting showed that HBsAg bound to a protein of 80 kD in human whey, which was identified as lactoferrin by mass spectrometry. Competitive inhibition immunoassays further demonstrated that both human lactoferrin and bovine lactoferrin bound to HBsAg. Human whey, human lactoferrin, and bovine lactoferrin each significantly inhibited the infectivity of HBV in vitro. Our results indicate that human breastmilk can bind to HBsAg and inhibit the infectivity of HBV, and the active component is lactoferrin. The findings may explain the reason that breastfeeding has no additional risk for MTCT of HBV, although human breastmilk contains HBV. Our study provides experimental evidence that HBV-infected mothers should be encouraged to breastfeed their infants     

双极电凝镊在扁桃体摘除术中的应用

目的：通过比较采用双极电凝镊与传统的剥离法实施扁桃体摘除的手术效果,探讨双极电凝镊在扁桃体摘除术中的应用效果。方法：选取行扁桃体手术摘除的患者100例,前瞻性地分为两组,比较手术时间、术中出血量及术后患者并发症、疼痛程度及恢复时间。结果：用双极电凝镊行扁桃体摘除与普通法扁桃体摘除相比,手术时间短,术中出血少,术后并发症发生率低,患者痛苦轻。结论：采用双极电凝镊扁桃体摘除手术效果明显优于普通剥离法扁桃体摘除,两方法术后恢复时间无统计学差别。     

Association of Vitamin D in Different Trimester with Hemoglobin during Pregnancy

The association between vitamin D and hemoglobin has been suggested. Vitamin D can affect erythropoiesis by the induction of erythroid progenitor cell proliferation and enhance iron absorption by regulating the iron-hepcidin-ferroportin axis in monocytes. However, this relationship in pregnant women is scarce. The purpose of this study was to investigate the association between plasma vitamin D levels with hemoglobin concentration in pregnant women considering each trimester and iron supplementation. The data were obtained from Zhoushan Pregnant Women Cohort, collected from 2011 to 2018. Plasma 25(OH)D was measured in each trimester using liquid chromatography–tandem mass spectrometry. Generalized estimating equations and multiple linear regressions were performed. Finally, 2962 pregnant women and 4419 observations in the first trimester were included in this study. Plasma 25(OH)D in first trimester (T1) (β = 0.06, p = 0.0177), second trimester (T2) (β = 0.15, p < 0.0001), and third trimester (T3) (β = 0.12, p = 0.0006) were positively associated with Hb. Association between plasma 25(OH)D levels in T1 and Hb concentration was positively associated with gestational age (β = 0.005, p = 0.0421). Pregnant women with VD deficiency in T1 (OR = 1.42, 95% CI: 1.07–1.88) or T2 (OR = 1.94, 95% CI: 1.30–2.89) presented an increased risk of anemia, compared with women without VD deficiency. Moreover, the significant relationship between VD and Hb was only observed among women with iron supplementation during pregnancy. Plasma 25(OH)D levels in each trimester were positively associated with Hb concentration. Iron supplementation might be an important factor affecting the relationship between VD and Hb.