Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

Hypofractionated radiation therapy for invasive breast cancer: From moderate to extreme protocols

Adjuvant irradiation is the standard treatment after breast conservative surgery. Normofractionated regimen with an overall treatment time of 5 to 6 weeks is often considered as a limiting factor for irradiation compliance. In order to answer this issue, moderate and more recently extreme hypofractionated protocols appeared. We report here oncological outcomes and toxicity of hypofractionated breast irradiation. After defining the frame of moderate and extreme hypofractionated breast irradiations based on overall treatment time, patient selection criteria were listed. According to their levels of proof, the results of moderate and extreme hypofractionated breast irradiation were analysed. Overall treatment time for moderate hypofractionated breast irradiation ranged from 3 to 4 weeks, while for extreme hypofractionated breast irradiation, it was less than 1 week. For moderate hypofractionated breast irradiation, whole breast irradiation was currently performed with or without lymph node irradiation. Moderate hypofractionated breast irradiation has proven to be as safe and as efficient as normofractionated breast irradiation with level IA evidence. For extreme hypofractionated breast irradiation, phase III randomized trials confirmed that accelerated partial breast irradiation was non-inferior in terms of local control compared to normofractionated whole breast irradiation (with external beam radiation therapy and multicatheter brachytherapy), with similar acute and late toxicity. While the use of intraoperative breast irradiation remains under debate, new very accelerated partial breast irradiation (overall treatment time not exceeding 2 days) protocols emerged with encouraging results. Accelerated partial breast irradiation is warranted for extreme hypofractionated breast irradiation and is indicated for low-risk breast cancers. Moderate and extreme hypofractionated breast irradiation regimens are validated and can be routinely proposed according to patient selection criteria.     

新型冠状病毒核酸检测在眼科医院疫情防控中的实践与有效性研究

目的:探索以系统化、标准化的新型冠状病毒核酸检测为核心和重要组成部分,建立适合于眼科医院新冠疫情精准防控切实可行的防控体系。方法:系列病例研究。自2020年2月24日至3月2日期间,以标准化病毒核酸检测联合血常规、C反应蛋白(CRP)、血清淀粉样蛋白A(SAA)等检测作为所有眼科手术患者术前筛查常规检测项目,同时也为返岗员工提供病毒核酸检测。设计调查问卷了解受检者对鼻咽拭子采样的接受度以及核酸检测结果对其心理状态的影响。结果:99例患者血液学检测结果有一定的异常比例,其中SAA检测结果增高13例,淋巴细胞计数减低12例、增高5例,白细胞计数增高11例、减低1例,CRP增高2例,新型冠状病毒核酸检测均阴性。33例本院职工新型冠状病毒核酸检测均阴性。12%的受访者对鼻咽拭子采样接受度评分较低。受检者在核酸检测前后思想压力评分较高的比例分别为46.7%和6.7%。结论:该项举措一方面为术前新冠病毒肺炎筛查及鉴别诊断提供了客观依据,很大程度上排除了隐性无症状感染者传播的可能,有利于减少二次传播的风险,降低院内交叉感染的概率;另一方面,核酸检测阴性结果有利于调整患者术前的心理状态并缓解医护人员在疫情防控期间的心理压力。     

An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers

Radiodermatitis is one of the commonest side effects of radiotherapy. They are usually assessed by semi‐quantitative clinical scores, which are not validated and may be subject to inter‐observer variability. A few previous studies suggested that high‐frequency ultrasonography (HF‐USG) is useful in the assessment of the acute phase of radiation dermatitis in breast cancer patients. (a) To monitor skin changes by HF‐USG during the course of radiotherapy due to head and neck cancers, and (b) to determine whether there is any connection between skin sonograms and the skin scoring criteria. This prospective, observational study includes patients diagnosed with head and neck cancers, treated with radiotherapy or concomitant chemoradiation. The final analysis includes six patients. In every patient, the HF‐USG as well as dermatological assessment (target lesion score—TLS and CACE v. 4.0) were performed 4×: before, in the middle, day after, and 3 months after radiotherapy. There were significant differences between non‐irradiated skin thickness and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P < .0001), as well as between irradiated, unchanged skin thickness (TLS grade 0) and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P = .0002). There was no significant difference between non‐irradiated and irradiated, unchanged skin thickness (TLS grade 0; P = .9318). In four patients, we demonstrated subepidermal low echogenic band (SLEB). HF‐USG can be useful tool to noninvasive and objective assessment of skin changes during radiotherapy.     

腹腔镜胆囊切除术治疗急性结石性胆囊炎的疗效

目的探讨分析对急性结石性胆囊炎患者采用腹腔镜胆囊切除术进行治疗的临床效果,以及对患者的胃肠功能和C反应蛋白所造成的影响。方法本次研究对象乃是我院肝胆外科于2017年4月-2019年4月期间收治的急性结石性胆囊炎患者62例,按照患者就诊的先后顺序对其进行平均分组,比较两组患者的术后肠鸣音恢复时间、肛门排气时间、排便时间、C反应蛋白水平以及并发症发生率。结果腹腔镜手术组患者的术后肠鸣音恢复时间(13.6±3.5)小时、肛门排气时间(16.5±2.7)小时以及排便时间(25.7±3.3)小时,均明显少于开腹式手术组患者(P<0.05);腹腔镜手术组患者的术后并发症发生率(6.45%)明显低于开腹式手术组患者(25.80%)(P<0.05);腹腔镜手术组患者的C反应蛋白水平为(10.4±2.5)mg/L,少于开腹式手术组患者(P<0.05)。结论根据本次研究的结果可以确认,对急性结石性胆囊炎患者采用腹腔镜胆囊切除术进行治疗能够取得更好的效果,可以促使患者的胃肠功能在术后更快的恢复,提高患者的C反应蛋白,从而有效避免患者出现并发症。