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Boyi Niu Yixian Zhou Kaixin Liao Ting Wen Sixian Lao Guilan Quan Xin Pan Chuanbin Wu 《药学学报(英文版)》2022,12(4):2074
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 相似文献
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Hailin Xiong Miaochan Lao Shuyi Zhang Jialian Chen Qianping Shi Yanxia Xu Qiong Ou 《Journal of gastrointestinal oncology.》2022,13(2):683
BackgroundThe association between colorectal cancer (CRC) and obstructive sleep apnoea (OSA) has been attracting increasing attention. several studies had confirmed that OSA increases the risk of CRC onset. However, the findings of studies on the morbidity of OSA in patients with CRC were unclear. Therefore, this study aimed to investigate the morbidity of OSA in patients with CRC as well as the association between the clinicopathological characteristics of OSA and CRC.MethodsA total of 414 patients with a pathological diagnosis of CRC from 1 January, 2020 to 30 December, 2020 were included in this study. Demographic characteristics, clinical information, and tumor characteristics of participants were collected; sleep was monitored using a wearable oximeter and via sleep quality questionnaire. The oxygen desaturation index (ODI) was used to classify OSA severity so that the diagnostic criteria for OSA were set based on the ODI as 0–5 (normal) and ≥5 (abnormal). After correcting for confounding factors, a logistic regression analysis was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) for the factors affecting the tumor lymph node stage (N stage).ResultsA total of 402 patients with CRC were included in this study, including 225 (55.97%) men and 177 (44.03%) women. The mean ODI value of participants was 3.40±8.17. The morbidity of OSA among the patients with CRC having ODI ≥5 was 16.17%. A comparison between the normal and abnormal ODI value groups revealed that the high proportion of abnormal ODI was related to higher N stage (P<0.05). Logistic regression analysis revealed a correlation of ODI values and age to the N stage. Specifically, CRC patients with an abnormal ODI had a higher risk of lymph node metastasis compared to those with normal ODI (OR =1.915, 95% CI: 1.025 to 3.579). Moreover, patients with CRC aged ≥65 years had a higher risk of lymph node metastasis compared to those aged <65 years (OR =2.190, 95% CI: 1.163 to 4.125).ConclusionsCRC patients with abnormal ODI are susceptible to OSA. Additionally, abnormal ODI and age ≥65 years are relevant factors for the N2 stage. 相似文献
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手术治疗老年股骨转子间骨折 总被引:7,自引:4,他引:7
目的探讨手术治疗老年股骨转子间骨折的效果。方法用国产Richards钉、130°角钢板(新型氮化钛自动加压梯形钢板)及加压螺钉3种内固定技术治疗不同类型老年股骨转子间骨折82例。结果稳定型骨折术后优良率100%,不稳定型骨折术后优良率92%;3种术式优良率:Richards钉45/48,130°角钢板19/20,加压螺钉3/3。结论老年股骨转子间骨折以手术治疗为宜,手术方式应根据患者情况和骨折稳定程度决定。 相似文献
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目的探讨锁定加压钢板治疗复杂胫骨平台骨折的临床效果。方法选择我院2008年1月至2011年1月复杂胫骨平台骨折患者82例,其中男49例,女33例,平均年龄为33.8±6.8岁,均行手术治疗,实施锁定加压钢板内固定治疗。结果本组患者随访时间为10~36个月,3例失访,79例患者骨折均愈合,术后没有出现骨筋膜室综合症,没有患者出现下肢深静脉血栓形成。骨折骨性愈合平均时间为5个月;术后没有患者出现断钉、钢板断裂等;其中1例患者出现小范围皮肤坏死,经游离植皮等处理后愈合。2例伤口出现轻度感染,经抗感染治疗后控制并治愈。无患者出现明显膝关节僵硬,无患者合并排总神经损伤。按Rasmussen评分标准,优良率为82.9%。结论锁定加压钢板治疗复杂性胫骨平台骨折膝关节功能恢复效果显著,临床效果显著。 相似文献
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目的 探讨获得性免疫缺陷综合征(AIDS)患者骨髓细胞形态学特征,为快速诊断AIDS以及预后提供依据。方法 回顾性分析广西医科大学第一附属医院行HIV检查的疑似AIDS患者60例,对其中HIV阳性患者行骨髓细胞学检查,并对检查结果进行统计学分析。结果 AIDS患者取材60份,取材满意度为100%。其中马尔尼菲青霉菌(PM)检出8例、淋巴瘤细胞检出1例;有核细胞增生活跃57例,粒红细胞比值升高27例、降低26例;骨髓细胞常见异常表现型分布前3的依次为:淋巴细胞减少、红细胞核形态异常、红细胞缗钱状排列。截止最后随访时间,60例HIV阳性患者死亡27例,总生存率为45.0%,增生活跃者死亡率为11.67%,低于增生不活跃者(P?<0.05)。结论 AIDS患者的骨髓细胞学特点主要表现为粒细胞、红细胞、巨核细胞系统一系或多系病态造血,淋巴细胞比率降低,常伴组织细胞反应性增殖或活化,骨髓细胞检测可以用于AIDS的筛查。 相似文献
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Welch WJ Mendonca M Blau J Karber A Dennehy K Patel K Lao YS José PA Wilcox CS 《Kidney international》2005,68(1):179-187
INTRODUCTION: Tempol is a permeant nitroxide superoxide dismutase (SOD) mimetic that lowers mean arterial pressure (MAP) in spontaneously hypertensive rats (SHRs). We investigated the hypothesis that the antihypertensive response entails a negative salt balance, blunting of plasma renin activity (PRA), endothelin-1 (ET-1), or catecholamines or correction of oxidative stress as indexed by 8-isoprostane prostaglandin F(2alpha) (PGF(2alpha)) (8-Iso). METHODS: Groups (N= 6 to 8) of SHRs were infused for 2 weeks with vehicle or tempol (200 nmol/kg/min) or given tempol (2 mmol/L) in drinking water. RESULTS: Tempol infusion reduced the MAP of anesthetized SHRs (150 +/- 5 vs. 126 +/- 6 mm Hg) (P < 0.005). Oral tempol did not change the heart rate but reduced the MAP of conscious SHRs (-23 +/- 6 mm Hg) (P < 0.01) but not Wistar-Kyoto (WKY) rats. Tempol infusion increased the PRA (2.2 +/- 0.2 vs. 5.0 +/- 0.9 ng/mL/hour) (P < 0.005), did not change excretion of nitric oxide (NO) [NO(2)+ NO(3) (NOx)], ET-1, or catecholamines but reduced excretion of 8-Iso (13.2 +/- 1.4 vs. 9.6 +/- 0.9 ng/24 hours; P < 0.01). Cumulative Na(+) balance and gain in body weight were unaltered by tempol infusion. Tempol prevented a rise in MAP with high salt intake. CONCLUSION: Tempol corrects hypertension without a compensatory sympathoadrenal activation or salt retention. The response is independent of nitric oxide, endothelin, or catecholamines and occurs despite increased PRA. It is accompanied by a reduction in oxidative stress and is maintained during increased salt intake. 相似文献
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目的:探讨改良功能性腮腺良性肿瘤切除术的临床效果和美学效果。方法:收集32例腮腺良性肿瘤病例,采用腮腺美容切口、保留耳大神经、腮腺区域性切除和SMAS筋膜填塞(或植入脱细胞真皮基质)等改良腮腺良性肿瘤切除术,随访6~24个月,通过问卷调查患者面部外形满意度、腮腺区味觉出汗症状和术区感觉恢复情况,临床检查和淀粉碘试验评价面部外形、面神经功能和Freys综合征。结果:术后切口均Ⅰ期甲级愈合,随访6~24个月,腮腺区外形良好,凹陷畸形不明显。28例面神经功能评价为House-Brackmann分级Ⅰ级,4例为II级;3例术侧耳垂麻木,术后3~8个月触觉、痛觉和温度觉逐渐恢复;1例出现Freys综合征;术后美容效果满意率100%。结论:应用改良腮腺良性肿瘤切除术尽可能保留了术后腮腺功能,有效减少了术后多种并发症的发生,获得了良好的美学效果。 相似文献