Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

Effectiveness of a double-carbapenem combinations against carbapenem-resistant Gram-negative bacteria

The emergence of carbapenem-resistant organisms posed considerable threat to global health while only limited treatment options are available and led to efforts to discover a novel way to treat them. To evaluate in vitro synergistic activity of meropenem plus ertapenem, a total of 203 carbapenem-resistant strains, collected from 12 provinces and municipalities in China, were examined with a dual carbapenem combination therapy. The statistical software R was used for analysis. Two hundred and one (201) of carbapenem-resistant strains mainly produced four types of carbapenemase: KPC-2 (n = 142, 69.95%), OXA-232 (n = 7, 3.45%), NDM (n = 38, 18.72%; 36 NDM-1, 1 NDM-4, 1 NDM-5), and IMP (n = 15, 7.39%; 1 IMP-26, 10 IMP-30, 4 IMP-4). Fifty-one out of two hundred and three (51/203 or 25.12%) of the examined strains showed a synergistic effect for the meropenem plus ertapenem combination throughout the checkerboard method, while only three isolates showed potential clinically relevant synergy (3/203, 1.48%). An additive effect was observed in 55/203 (27.09%) of the examined strains. Ninety-seven of the examined isolates (47.78%) showed fractional inhibitory concentration (FIC) greater or equal to 2 (indicating antagonism). The synergistic activity of meropenem plus ertapenem combination suggests this combination can be a possible way to treat the infection caused by the carbapenem-resistant organisms, especially for IMP or NDM producer with a lesser minimum inhibitory concentration (MIC) and the infected individual who was not recommended to use colistin or tigecycline.     

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.     

PERK信号通路介导结肠癌细胞对5-氟尿嘧啶耐药机制的研究

目的:观察PERK蛋白对结肠癌细胞药物敏感性的影响，并进一步探讨其相关作用机制。方法:结肠癌细胞系HCT116分为三组:空白对照（Control）组、下调PERK表达（si-PERK）组、阴性对照（si-NC）组；采用免疫荧光及RT-PCR验证转染效率；利用CCK-8实验检测下调PERK表达后结肠癌细胞对化疗药物5-FU的敏感性变化；Annexin V-FITC凋亡实验检测下调PERK表达对结肠癌细胞凋亡的影响；利用RT-PCR及Western Blot实验检测PERK信号通路中关键分子eIF2α、ATF4、CHOP、XIAP的mRNA及蛋白表达变化。结果:RT-PCR实验表明:与正常对照组相比，si-PERK 组mRNA的表达显著下降（P＜0.05）,免疫荧光提示转染效率达80%以上；CCK-8实验发现与si-NC组相比，5-FU对 si-PERK组细胞的半数抑制浓度（IC50）明显降低（P＜0.01）；Annexin V-FITC凋亡实验发现与si-NC组相比，si-PERK组细胞的凋亡发生率显著升高（P＜0.05）；RT-PCR及Western Blot实验发现与si-NC组相比，si-PERK组细胞中PERK信号通路下游关键分子eIF2α、ATF4、CHOP的mRNA及蛋白表达均明显降低（P＜0.05）。结论:在结肠癌细胞中，抑制PERK表达后，其可能通过下调eIF2α、ATF4、CHOP的表达促进细胞发生凋亡，从而促进细胞对化疗药物5-FU的敏感性。     

Short-Duration Prednisolone in Children with Nephrotic Syndrome Relapse: A Noninferiority Randomized Controlled Trial

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不同药物方案治疗儿童双相情感障碍疗效比较及代谢指标观察

目的 探讨儿童双相情感障碍经不同药物方案治疗后代谢指标的变化及治疗疗效。方法 回顾性分析2017年1月至2020年1月于该院就诊的220例儿童双相情感障碍患儿的临床资料。根据治疗方法分组，单纯采用非典型抗精神病药物治疗的112例患儿纳入对照组，采用非典型抗精神病药物联合心境稳定剂治疗的108例患儿纳入研究组。比较两组基线资料水平，治疗前后代谢指标空腹胰岛素（FIN）、糖化血红蛋白（HbAlc）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平变化，以及代谢综合征发生情况及临床疗效。结果 两组患儿年龄、性别、病程等基线资料比较差异均无统计学意义（P > 0.05）。研究组总有效率为92.6%，高于对照组（82.1%，P < 0.05）。治疗前，两组FIN、HbAlc水平比较差异无统计学意义（P > 0.05）；治疗后，对照组FIN水平高于治疗前，且高于研究组（P < 0.05）；但研究组治疗前后FIN水平比较差异无统计学意义（P > 0.05）；两组治疗前后HbAlc水平比较差异无统计学意义（P > 0.05）。治疗前，两组TC、TG、HDL-C、LDL-C水平比较，差异无统计学意义（P > 0.05）；治疗后，对照组TC、TG水平均高于治疗前，且高于研究组（P < 0.05）；但研究组治疗前后TC、TG水平比较差异无统计学意义（P > 0.05）；两组治疗前后HDL-C、LDL-C水平比较差异无统计学意义（P > 0.05）。研究组代谢综合征发生率（2.8%）低于对照组（9.8%）（P < 0.05）。结论 儿童双相情感障碍采用非经典抗精神病药物联合心境稳定剂治疗对代谢指标水平影响较小，且疗效显著。     

新氨基糖苷类抗生素89－07给药方案研究

用小鼠败血症系统感染模型，以感染小鼠肾匀浆活菌计数为标准，以庆大霉素为对照药，探讨日剂量单次与分两次给药两种方案对新氨基糖苷类抗生素８９—０７体内抗留作用的影响。结果表明大肠杆菌９０－０２０、绿脓假单胞菌３—３７４、金葡球菌９０—５０６对抗生素８９—０７和庆大霉素均敏感（ＭＩＣ范围０．０６２５～２ｍｇ／Ｌ）；抗生素８９—０７和庆大霉素日剂量单次给药组（ＯＤ）３株实验菌的肾匀浆活菌计数值由给药前的４．９４±０．０９、４．６０±０．２７、４．８６±０．１０１ｇｃｆｕ／ｍｌ分别降至１．９４±０．１９、１．８４±０．２５、１．８８±０．２５１ｇｃｆｕ／ｍｌ（给药后７～８ｈ）．日剂量分两次给药组（ＢＩＤ）则分别降至２．９５±０．４８、２．８７±０．３７、３．４４±０．２７１ｇｃｆｕ／ｍｌ。ＯＤ组对３株实验菌的最大杀菌作用Ｅｍａｘ分别为３．０２、２．９７和２．８５１ｇｃｆｕ／ｍｌ，ＯＤ给药方案的体内杀菌作用明显优于ＢＩＤ方案。     

Influence of tumours on normal cells and optimal chemotherapy regimens: the case of several drugs and toxicity constraints.

Cancer chemotherapy with the application of several drugs is studied. The negative and inhibiting effect of the tumour on normal cells is taken into account. Under certain hypotheses, we determine the optimal regimen that minimizes the tumour burden at the end of a fixed period of therapy while maintaining several normal cell populations above prescribed levels. More precisely, it is demonstrated that the optimal drug administration corresponds to the strategy of intensive chemotherapy.     

血肌酐值法预测地高辛个体化给药方案

在地高辛常规监测中，用血肌酐值法预测个体化药动学参数和给药方案。结果表明，８４例病人的地高辛药物动力学参数预测值为，ＣＬ７６±２１ｍｌ／（ｋｇ·ｈ），Ｖｄ７．０５±１．２０Ｌ／ｋｇ，Ｔ１／２６６±７ｈ。预测的个体化剂量为３．１±０．９μｇ／（ｋｇ·ｄ），预测的稳态血药浓度（Ｃ＿（ｓｓ））为１．２４±０．３８μｇ／Ｌ，与实测Ｃ＿（ｓｓ）１．２±０．４μｇ／Ｌ比较，差异无显著性（Ｐ＞０．０５）。     

非霍奇金淋巴瘤采用CHOP方案治疗与护理

目的探讨NHL采用CHOP方案治疗中护理的重要性.方法对115例NHL采用CTX,750mg/m2 静滴第1日,VCR 1.4g/m2静滴第1.8日,PDN100mg/m2PO第1～5日,每21天为1周期,本组病例用药4～6个周期.结果顺利地完成了115例NHL的化疗,无1例出现化疗作用.结论肿瘤专科护理的措施是顺利完成化疗,减轻副作用,提高生活质量的保证.