Adropin 蛋白在多囊卵巢综合征中的研究进展及临床意义

多囊卵巢综合征 (polycystic ovary syndrome, PCOS) 是一种在育龄期女性中常见的疾病, 它的主 要临床表现是月经紊乱、 不孕、 痤疮、 多毛等症状, 可能伴随有糖脂代谢异常。 Adropin 是新近发现的一种 分泌性蛋白, 已证实其在调节糖脂代谢、 改善胰岛素抵抗中发挥着作用, 但具体作用机制及其临床意义尚 未完全明确。 文章简要综述 Adropin 蛋白的作用机理及其在多囊卵巢综合征中的研究进展及临床意义。     

Performance of the new FilmArray Blood Culture Identification 2 panel and its potential impact on clinical use in patients with Gram-negative bacteremia

IntroductionRapid diagnostic tests have been developed recently for rapid species or resistance genes identification, offering the potential to improve the selection of appropriate antibiotics. The newly developed FilmArray Blood Culture Identification 2 (BCID2) panel, which can identify more species and resistance genes, such as extended-spectrum beta-lactamase, is expected to make an impact on antimicrobial practice.MethodsThe consecutive 50 inpatients with Gram-negative bacilli bacteremia were enrolled to this retrospective single-center study. In addition to the existing FilmArray Blood Culture Identification (BCID) panel, we have implemented BCID2 panel for positive blood culture. The sensitivity and specificity of BCID and BCID2 panel were respectively calculated, and a simulation study of time to effective, optimal and de-escalation therapy was performed based on BCID or BCID2 result.ResultsA total of 52 Gram-negative organisms in 50 patients were identified from blood cultures. Of these, 45 (87%) organisms were detected by BCID2 panel, which was more than BCID panel (41 organisms, 79%). BCID2 panel detected 5 CTX-M genes, which were concordant with conventional method. The time to effective therapy did not differ between BCID arm and BCID2 arm; however, the median time to optimal therapy (34 h in BCID arm and 26 h in BCID2 arm, P = 0.0007) and the median time to de-escalation therapy (42 h in BCID arm and 22 h in BCID2 arm, P = 0.0005) were significantly shortened.ConclusionsThis simulation study of BCID2 panel showed high sensitivity and specificity, and the potential impact on shortening the time to optimal and de-escalation therapy.     

宫颈癌免疫治疗的耐药机制及应对措施

宫颈癌严重威胁全球女性的生命健康，晚期宫颈癌治疗手段有限，5年生存率不到20%，是妇科肿瘤的巨大挑战。免疫治疗是晚期宫颈癌患者的重要治疗手段之一，包括免疫检查点抑制剂、治疗性疫苗和过继性T细胞免疫疗法等，但免疫治疗耐药性使部分患者无应答而效果不佳。因此，迫切需要深入研究和探讨免疫耐药的机制从而改善耐药，现归纳总结了近年有关宫颈癌中免疫耐药机制的相关研究，主要分为肿瘤内在因素和外在免疫环境改变等因素，并介绍针对免疫耐药提出的应对措施及进展。     

非小细胞肺癌顺铂耐药相关基因生物信息学研究

目的：通过分析非小细胞肺癌顺铂敏感株及耐药株的基因芯片表达数据，筛选差异基因及关键通路，构建蛋白相互作用网络，探讨关键集群功能。方法:从GEO数据库获得基因芯片表达数据，利用GEO2R工具筛选差异基因，通过STRING数据库和Cytoscape软件构建蛋白相互作用网络，经DAVID富集得到相关特征基因与信号通路信息。结果：通过芯片分析共获得481个差异表达基因，相比于敏感细胞株，顺铂获得性耐药细胞株中有418个上调基因和63个下调基因。差异基因功能主要富集在piRNA代谢、DNA甲基化修饰、细胞有丝分裂及细胞周期进程等信号通路。蛋白复合物预测得到主要功能集群6个，分别与细胞趋化性、细胞角化性、piRNA代谢过程、细胞因子受体相互作用、细胞因子分泌调节及染色质沉默相关生物进程相关。结论:本研究利用生物信息学方法，发现顺铂耐药细胞株特征基因及信号通路，其中SAA1、KRT5、TDRD9、BCL2A1、CSF1R和HIST1H1A等显著上调基因及其功能集团可能是非小细胞肺癌顺铂耐药的潜在分子机制，为临床精准治疗提供新的理论依据。     

Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression

Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future.     

免疫编辑诱导的免疫治疗耐药

近年来，免疫治疗在多种恶性肿瘤治疗中取得突破性进展，为肿瘤患者带来明显生存获益。然而，免疫系统在识别和杀伤肿瘤细胞的同时，出现免疫编辑诱导，导致大多数患者对免疫治疗具有先天或后天的耐药性。肿瘤免疫编辑是免疫系统抑制或促进肿瘤发生发展的过程，肿瘤的发生发展经历了免疫消除、免疫平衡和免疫逃逸三个阶段。在整个过程中，肿瘤的免疫原性被编辑，并获得使疾病进展的各种免疫抑制机制，致使肿瘤细胞逃避免疫系统的监测，导致肿瘤细胞免疫逃逸产生耐药。因此，揭示肿瘤免疫治疗耐药机制及克服耐药至关重要。本文主要从肿瘤免疫编辑过程背后的机制对肿瘤免疫治疗耐药作一具体阐述，为临床中克服免疫耐药取得更好疗效提供参考。     

Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cells in vitro and in vivo

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [¹²⁵I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.     

Antibiotic resistant bacteria and resistance genes in biofilms in clinical wastewater networks

Increasing isolation rates of resistant bacteria in the last years require identification of potential infection reservoirs in healthcare facilities. Especially the clinical wastewater network represents a potential source of antibiotic resistant bacteria. In this work, the siphons of the sanitary installations from 18 hospital rooms of two German hospitals were examined for antibiotic resistant bacteria and antibiotic residues including siphons of showers and washbasins and toilets in sanitary units of psychosomatic, haemato-oncological, and rehabilitation wards. In addition, in seven rooms of the haemato-oncological ward, the effect of 24 h of stagnation on the antibiotic concentrations and MDR (multi-drug-resistant) bacteria in biofilms was evaluated. Whereas no antibiotic residues were found in the psychosomatic ward, potential selective concentrations of piperacillin, meropenem and ciprofloxacin were detected at a rehabilitation ward and ciprofloxacin and trimethoprim were present at a haemato-oncology ward. Antibiotic resistant bacteria were isolated from the siphons of all wards, however in the psychosomatic ward, only one MDR strain with resistance to piperacillin, third generation cephalosporins and quinolones (3MRGN) was detected. In contrast, the other two wards yielded 11 carbapenemase producing MDR isolates and 15 3MRGN strains. The isolates from the haemato-oncological ward belonged mostly to two specific rare sequence types (ST) (P. aeruginosa ST823 and Enterobacter cloacae complex ST167). In conclusion, clinical wastewater systems represent a reservoir for multi-drug-resistant bacteria. Consequently, preventive and intervention measures should not start at the wastewater treatment in the treatment plant, but already in the immediate surroundings of the patient, in order to minimize the infection potential.