噻托溴铵治疗稳定期慢性阻塞性肺疾病的疗效评价

噻托溴铵是新一代治疗慢性阻塞性肺疾病(COPD)的吸入型长效抗胆碱药物,通过选择性作用于M1和M3受体,扩张支气管,疗效持续,每天只需使用一次.UPLIFT研究结果进一步证实,长期规律使用噻托溴铵能够改善中重度、极重度稳定期COPD患者肺功能情况,缓解症状、提高运动耐量及改善生活质量,延长急性发作的时间间隔、减少急性加重发作次数,降低COPD患者死亡率,具有良好的安全性.     

M与m-bcr/abl融合基因转录子共表达与 CML患者血小板增多的关系

目的 研究共表达m-bcr/abl融合基因转录子对初诊慢性髓系白血病(CML)患者的巨核细胞形态的影响.方法 分别用逆转录-聚合酶链反应(RT-PCR)和巢式PCR检测M和m-bcr/abl融合基因转录子.盲法计数患者骨髓涂片1.0 cm×1.5 cm2面积内巨核细胞数,随机选取20个巨核细胞分类计数并测定成熟期巨核细胞直径;计数产板型巨核细胞产血小板数.结果 107例初诊CML患者M和m-bcr/abl共表达者56例,b3a2型31例,b2a2型25例.共表达m-bcr/abl的b3a2型初诊CML患者血小板数比单表达M-bcr/abl和b2a2型m-bcr/abl( )患者高(P＜0.05).对巨核细胞形态观察,在b3a2和b2a2组,共表达m-bcr/abl和单表达M-bcr/abl的患者骨髓1.0 cm×1.5 cm面积内巨核细胞数、成熟巨核细胞数和直径差异均无统计学意义(P＞0.05);共表达m-bcr/abl的b3a2型患者产板型巨核细胞产板数比单表达M-bcr/abl患者高(P＜0.05);而b2a2型的共表达m-bcr/abl组和单表达M-bcr/abl组1.0 cm × 1.5 cm面积内巨核细胞数、成熟巨核细胞数和直径及产板型巨核细胞产板数差异均无统计学意义(P＞0.05).结论 共表达m-bcr/abl的b3a2型初诊CML患者血小板数增高是由其巨核细胞产板数多造成的,而与其巨核细胞数、产板型巨核细胞数和直径无关.     

SUMOylation of Kir7.1 participates in neuropathic pain through regulating its membrane expression in spinal cord neurons

AimsPotassium (K⁺) channels have been demonstrated to play a prominent involvement in nociceptive processing. Kir7.1, the newest members of the Kir channel family, has not been extensively studied in the CNS, and its function remains largely unknown. The present study investigated the role of spinal Kir7.1 in the development of pathological pain.Methods and ResultsNeuropathic pain was induced by spared nerve injury (SNI). The mechanical sensitivity was assessed by von Frey test. Immunofluorescence staining assay revealed that Kir7.1 was predominantly expressed in spinal neurons but not astrocytes or microglia in normal rats. Western blot results showed that SNI markedly decreased the total and membrane expression of Kir7.1 in the spinal dorsal horn accompanied by mechanical hypersensitivity. Blocking Kir7.1 with the specific antagonist ML418 or knockdown kir7.1 by siRNA led to mechanical allodynia. Co‐IP results showed that the spinal kir7.1 channels were decorated by SUMO‐1 but not SUMO‐2/3, and Kir7.1 SUMOylation was upregulated following SNI. Moreover, inhibited SUMOylation by GA (E1 inhibitor) or 2‐D08 (UBC9 inhibitor) can increase the spinal surface Kir7.1 expression.ConclusionSUMOylation of the Kir7.1 in the spinal cord might contribute to the development of SNI‐induced mechanical allodynia by decreasing the Kir7.1 surface expression in rats.     

Extracellular ATP promotes angiogenesis and adhesion of TNBC cells to endothelial cells via upregulation of CTGF

Our previous works have indicated that extracellular ATP is an important prometastasis factor. However, the molecular mechanism involved needs to be further studied. We demonstrated that extracellular ATP treatment could upregulate the expression of connective tissue growth factor (CTGF) in both triple‐negative breast cancer (TNBC) cells and endothelial cells (ECs). Extracellular ATP stimulated the migration of TNBC cells and ECs, and angiogenesis of ECs via the P2Y2––YAP‐CTGF axis. Furthermore, we demonstrated that adenosine triphosphate (ATP) stimulated TNBC cell adhesion to ECs and transmigration through the EC layer via CTGF by upregulation of integrin β1 on TNBC cells and VCAM‐1 on ECs. Both apyrase (ATP‐diphosphohydrolase) and CTGF shRNA treatments could inhibit the metastasis of inoculated tumors to lung and liver in a mouse model, and these treated tumors had fewer blood vessels. Collectively, our data indicated that extracellular ATP promotes tumor angiogenesis and the interactions between TNBC cells and ECs through upregulation of CTGF, thereby stimulating TNBC metastasis. The pleiotropic effects of ATP in angiogenesis and cell adhesion suggest that extracellular ATP or CTGF could be an effective target for TNBC therapy.     

“Pincer movement”: Reversing cisplatin resistance based on simultaneous glutathione depletion and glutathione S-transferases inhibition by redox-responsive degradable organosilica hybrid nanoparticles

The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers. Intracellular glutathione (GSH) detoxification of cisplatin under the catalysis of glutathione S-transferases (GST) plays important roles in the development of cisplatin resistance. Herein, a strategy of “pincer movement” based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy. Specifically, a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid (EA), a GST inhibitor. Responding to high level of intracellular GSH, the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds, which further promotes drug release. Meanwhile, the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance. Moreover, the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma. The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion, GST inhibition, and consequent tumor growth suppression. Overall, this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance, which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.KEY WORDS: Cancer therapy, Cisplatin, Drug resistance, Glutathione depletion, Glutathione S-transferases, Disulfide bonds, Organosilica hybrid nanoparticles, Ethacrynic acid     

近五年针刺治疗慢性疼痛机制研究进展

针刺镇痛在临床上被广泛应用。针刺的神经传导通路与机体痛觉传导通路基本相似,对周围神经和中枢神经均有一定的影响,因此推断这可能是针刺缓解疼痛的一种调节机制。本文总结了近五年针刺治疗各种疼痛疾病的机制研究,从传导通路上分析得知针刺能激发神经元活性,改善周围神经的病理变化,增加神经元之间突触传递,修复受损的周围神经以缓解疼痛。此外,应用针刺或加用电针治疗痛症,能改善大脑内与疼痛相关各功能区之间的联系,对镇痛起到一定的中枢调控作用。在研究中还发现针刺能减少病变区炎性反应和细胞凋亡,增加细胞自噬和血管调节因子的表达。这些反应之间常存在一定的相互作用,共同缓解机体疼痛症状。然而,临床中针刺手法及辅助方法众多,治疗选取的相关穴位各异,根据疾病定位定性后选择最优组合方式是今后总结经验的重要目标。     

Avian IRF1 and IRF7 Play Overlapping and Distinct Roles in Regulating IFN-Dependent and -Independent Antiviral Responses to Duck Tembusu Virus Infection

Avian interferon regulatory factors 1 and 7 (IRF1 and IRF7) play important roles in the host’s innate immunity against viral infection. Our previous study revealed that duck tembusu virus (DTMUV) infection of chicken fibroblasts (DF1) and duck embryo fibroblasts (DEFs) induced the expression of a variety of IFN-stimulated genes (ISGs), including VIPERIN, IFIT5, CMPK2, IRF1, and IRF7. IRF1 was further shown to play a significant role in regulating the up-expression of VIPERIN, IFIT5, and CMPK2 and inhibiting DTMUV replication. In this study, we confirm, through overexpression and knockout approaches, that both IRF1 and IRF7 inhibit DTMUV replication, mainly via regulation of type I IFN expression, as well as the induction of IRF1, VIPERIN, IFIT5, CMPK2, and MX1. In addition, IRF1 directly promoted the expression of VIPERIN and CMPK2 in an IFN-independent manner when IRF7 and type I IFN signaling were undermined. We also found that non-structural protein 2B (NS2B) of DTMUV was able to inhibit the induction of IFN-β mRNA triggered by Newcastle disease virus (NDV) infection or poly(I:C) treatment, revealing a strategy employed by DTMUV to evade host’s immunosurveillance. This study demonstrates that avian IRF7 and IRF1 play distinct roles in the regulation of type I IFN response during DTMUV infection.     

三七总皂甙对实验性脑缺血脑血流及血脑屏障的影响作用

目的 观察三七总皂甙对脑缺血后再灌流期间血脑屏障及脑血流的影响。方法 利用大鼠局灶性脑缺血再灌流和全脑缺血再灌流损伤两种实验模型。结果 与相应对照组比较，不论是全脑缺血还是局灶性脑缺血1h后再灌注3d，应用三七总皂甙的各组动物及水肿明显减轻，血脑屏障通透性改善，大脑局部血流量显著增加。结论 三七总皂甙对脑缺血后脑水肿、血脑屏障、大脑局部血流量具有保护作用。     

英国伦理委员会的现状与分析

伦理委员会的主要职责是保护药物临床试验受试者的权益、安全和健康.现对英国伦理委员会的法律、法规、申请及审评程序等进行归纳分析,旨在对规范我国伦理委员会的运作具有参考借鉴作用.     

巩膜隧道切口和透明角膜切口对白内障超声乳化摘除术患者术后泪膜的影响

目的 探究巩膜隧道切口和透明角膜切口对白内障超声乳化摘除术患者术后泪膜的影响。 方法 选取2014年2月至2015年10月接受白内障超声乳化摘除手术的白内障患者86例为研究对象,按手术切口不同分为实验组和对照组,每组43例。实验组患者采用透明角膜切口行白内障超声乳化摘除术,对照组患者采用巩膜隧道切口进行手术,分别于术后第1、7、15和30天观察两种切口白内障超声乳化摘除术对患者泪膜功能的影响。 结果 术后第1、7、15天,实验组患者的泪膜破裂时间均较术前缩短,且实验组患者的泪膜破裂时间显著短于对照组;术后第30天,两组患者的泪膜破裂时间均较术前明显延长,差异有统计学意义(P均<0.05);术后第1、7、15、30天,两组患者的泪液分泌量均较术前明显增多,且实验组患者的泪液分泌量明显多于对照组,差异均有统计学意义(P均<0.05)。 结论 与巩膜隧道切口行白内障超声乳化摘除术比较,透明角膜切口对患者术后泪膜功能的影响较小,是更值得在临床推广的白内障超声乳化摘除术的一种切口方式。