基于国际健康分类架构构建新型冠状病毒病重症病区配对康复治疗模式及其效果

基于国际健康分类架构探讨构建新型冠状病毒病(COVID-19)配对康复治疗模式，并观察其对重症病区COVID-19危重患者的治疗效果。     

他山之石 何以攻玉:从脑出血国际临床研究现状看我国的规范化治疗

自发性脑出血病死率和病残率较高,但缺乏有效的治疗策略。我国的脑出血相关研究与国际先进水平存在一定差距。近年国际上一系列临床研究从不同角度探讨脑出血的治疗方式,对我国脑出血研究和规范化治疗具有十分重要的参考价值。我国的脑出血临床治疗经验和研究成果要想走向世界,必须开展高质量的临床试验。四川大学华西医院神经外科正在开展INTERACT3试验,以及准备开展STICHⅢ试验,希望能够推动中国脑出血研究事业的进步。     

Vinorelbine After Prior Treatment With Eribulin for Advanced Breast Cancer: A Single-Centre Experience Suggesting Cross-Resistance

IntroductionThe tubulin inhibitor, eribulin, improves survival for previously treated advanced breast cancer (ABC) compared to chemotherapy of physician's choice, including vinorelbine, an older anti-tubulin. Vinorelbine is commonly still used after eribulin, but potentially risks cross-resistance and its efficacy in this setting is unproven.Materials and MethodsA retrospective analysis of all patients who received vinorelbine after prior eribulin (VAE) 2011-2015 and a parallel cohort of consecutive patients who received vinorelbine without prior eribulin (VWE) for previously treated ABC between 2005 and 2011. Patient demographics, histopathological features, treatment duration and responses were recorded. The primary endpoint was progression-free survival from date of first vinorelbine for each cohort. Secondary endpoints included radiological response rate, and overall survival (OS).ResultsThirty-five VAE and 103 VWE patients were identified, all female, 71.4% and 78.6% were ER positive/HER2 negative, 8.6% and 6.8% HER2 positive, and 20.0% and 14.6% triple negative for VAE and VWE cohorts, respectively. The median number of lines of chemotherapy lines prior to vinorelbine was 4 (range 2-6) and 2 (range 0-4), respectively. Fifteen VAE patients (42.9%) received ≥1 line of chemotherapy between eribulin and vinorelbine. VAE and WWE Patients received a median of 3 cycles of vinorelbine (range 1-9 and 1-12, respectively). The median progression-free survival for VAE patients was 2.1 months and 2.0 months for VWE patients. No VAE patients were progression-free at 24 weeks, compared to 15.5% of VWE patients. Median OS from commencing vinorelbine was 4.3 months for VAE and 6.4 months for VWE patients.ConclusionVinorelbine was of limited benefit after prior eribulin in our study, suggesting cross-resistance. Even without prior eribulin, only 15% of patients experienced clinical benefit from vinorelbine monotherapy.     

Plant extract incorporated into glass ionomer cement as a photosensitizing agent for antimicrobial photodynamic therapy on Streptococcus mutans

BackgroundA plant extract (EB) incorporated into glass ionomer cement (GIG) could be a potential photosensitizer for Antimicrobial PDT (aPDT) against caries-microorganisms, replacing methylene blue (MB), due to the presence of chlorophyll. GIC + EB + aPDT could be an therapeutic alternative to dentin decontamination and sealing, allowing reduction of operative time.ObjectiveEvaluate Dioscorea altissima (EB) incorporated into GIC as a photosensitizer for aPDT against Streptococcus mutans.MethodsGroups (n = 24; ntotal = 192): G1-GIC; G2-GIC + LASER; G3-GIC/EB; G4-GIC/EB + LASER; G5-GIC+MB; G6-GIC + aPDT; G7-GIC/EB + MB; and G8 – GIC/EB+aPDT. In aPDT groups, MB was the photosensitizer. In LASER groups, MB was not used. The irradiation protocol was 660 nm/100 mW/5 J/150 J/cm²/50 s, with a 5-min pre-irradiation time for the MB groups. Antibacterial assays were carried out in 24-well microplates. The wells were completed with one milliliter of a S. mutans in BHI at 1.3 × 10⁸ CFU/mL suspension. After incubation, PDT or laser was performed. After MTT bacteria viability test, the data were submitted to the Kolgomorov-Smirnoff normality test, followed by one-way ANOVA and Tukey's posterior test, α < 0.05.ResultsGroup G6 showed significant inhibition (p < 0.001), followed by groups G4, G5, G7, and G8, which did not show significant differences among them (p > 0.05). Groups G2 and G3 also showed similar results (p > 0.05) and were the least active compared to the others.ConclusionsEB potentiated the antimicrobial action of GIC against S. mutans and laser irradiation over GIC/EB presented better antimicrobials results. The results indicate that EB could be a potential photosensitizer for aPDT.     

妊娠合并长QT间期综合征的研究进展

长QT间期综合征（long QT syndrome,LQTS）是一种由基因突变导致离子通道结构或功能异常的遗传性心脏疾病,心电图以QT间期延长及T波改变为特征,易发生心悸、晕厥、心律失常、心脏骤停甚至猝死等。LQTS患者临床最常见的基因亚型为LQT1型、LQT2型和LQT3型,不同基因亚型的LQTS在突变基因、触发因素甚至心电图改变上均有差异,明确患者基因亚型,有助于临床诊断、治疗及对心脏事件发生的预防。有效预防心脏事件发生对LQTS患者是最重要的措施之一;合并LQTS孕产妇在妊娠、产褥期将经历激素水平、血流动力学改变等一系列生理性变化,均可能影响LQTS相关心脏事件的发生风险;其临床管理也不同于非LQTS孕产妇,有必要了解其发病机制、诊断标准、治疗方案及围生期管理的研究进展。     

硫氧还蛋白相互作用蛋白在多囊卵巢综合征中作用的研究进展

多囊卵巢综合征（polycystic ovary syndrome，PCOS）是一种常见于育龄妇女的内分泌代谢性疾病，以月经不规则、高雄激素血症和卵巢多囊样改变为特征，常表现为肥胖、不孕和胰岛素抵抗。硫氧还蛋白相互作用蛋白（thioredoxin-interacting protein，TXNIP）是一种多功能调节剂，不仅参与胰岛素分泌和葡萄糖代谢的调节，还与氧化应激、炎症因子和情绪障碍密切相关。PCOS患者体内的TXNIP水平较健康人群明显增加，表明TXNIP可能参与PCOS及其并发症的发生、发展。近年体内外研究尝试应用中药提取物和西医药物抑制TXNIP的表达，TXNIP特异性抑制剂的发现使TXNIP有望成为抑制PCOS进程的有效靶点。综述TXNIP在PCOS中的作用进展，以期为PCOS发病机制的深入研究及临床诊疗提供新的思路和方向。     

Extracellular vesicles or free circulating DNA: where to search for BRAF and cKIT mutations?

Clinical evidence in oncology argues for the advantages of performing molecular analysis of blood biomarkers to provide information about systemic changes and tumor heterogeneity.Whereas the diagnostic value of cell-free circulating DNA (fcDNA) has successfully been demonstrated in several studies, DNA enclosed in extracellular vesicles (EV) has only recently been described, and its potential diagnostic value is unclear. We established a protocol for separation of EV and fc fractions and tested for presence of mutant BRAFV600E mediating resistance to Vemurafenib and cKITD816V mediating resistance to Imatinib in blood of patients with melanoma and mastocytosis. Our results show that EV contain significantly higher amounts of total DNA as compared to the fc fraction. However, about ten-fold higher copy numbers of the wild type and mutant BRAF and cKIT were detected in the fcDNA fraction supporting its diagnostic value and pointing to differences in fc and EV DNA content.     

重度烧伤后高代谢特征及临床治疗新进展

重度烧伤后机体应激导致神经内分泌调节紊乱,涉及机体长时间高强度的代谢反应、难以纠正的蛋白质代谢紊乱、长期的顽固高血糖及胰岛素低敏性等,不仅增加了营养支持和治疗困难,而且常常会增加机体感染概率、延迟组织修复,导致严重烧伤患者多器官功能障碍的风险增加。因此深入研究重度烧伤后高代谢,探索其有效的治疗方案一直是临床研究的热点。本文通过回顾近年来重度烧伤高代谢的特征及治疗进展,以期为临床救治提供切实可行的方法。     

Targeting Aurora kinase B attenuates chemoresistance in glioblastoma via a synergistic manner with temozolomide

BackgroundRecent studies have demonstrated that aberrant expression or activation of kinases results in oncogenesis of a wide range of cancers including GBM. Inhibition of kinases expression induces a reduction of therapy resistance. In this study, we investigate the underlying mechanism by which glioblastoma (GBM) cells acquire resistance to Temozolomide (TMZ) through Aurora kinase B (AURKB) thus to identify novel therapeutic targets and prognostic biomarkers for GBM.MethodsAURKB was identified as a key candidate kinase-encoding gene in chemoresistance regulation by using kinome-wide bioinformatic analysis. Afterwards, the potential biological functions of AURKB in oncogenesis and chemoresistance were investigated by lentivirus-dependent silencing of AURKB combined with qRT-PCR, western blot and in vivo intra-cranial xenograft mice models. Additionally, immunohistochemistry (IHC) assays were performed to explore the clinical significance of AURKB in glioma patients. Lastly, Chou-Talalay method was used to confirm the synergistic effect of TMZ combined with AURKB inhibitor.ResultsAURKB was among the most significantly up-regulated kinase-coding genes in TMZ resistant GBM cells according to database GSE68029, moreover, an increased expression of AURKB was closely associated with poor prognosis in glioma and GBM patients. AURKB knock-down resensitized U87 resistant cells to TMZ both in vitro and in vivo. Additionally, the combination of TMZ and Hesperadin, a specific AURKB inhibitor, significantly suppressed the proliferation of TMZ resistant GBM cells thus dramatically prolonged the survival of xenograft mice viaa synergistic effect with TMZ.ConclusionElevated AURKB expression was strongly correlated to TMZ resistant acquisition and poor prognosis, furthermore, targeting AURKB would be a potential therapeutic target for GBM patients.     

慢性炎症与多囊卵巢综合征的关系及相关研究进展

多囊卵巢综合征（PCOS）是发生于青春期或育龄期女性常见的内分泌失调性疾病,以排卵障碍、胰岛素抵抗（IR）和高雄激素血症（HA）为主要特征,是女性不孕症的主要原因之一。慢性炎症是机体发挥防御功能的重要途径之一,但也是代谢性疾病形成的原因之一。PCOS患者存在低度的慢性炎症,某些重要炎症因子的分泌水平异常升高,提示慢性炎症与PCOS发生、发展之间可能具有相关性,但尚存争议。已有研究表明,PCOS病理过程中释放一些炎症因子,引发慢性低度炎症。新近报道指出,慢性炎症可能在PCOS早期即参与了肥胖、IR和HA的发生;将某些具有抗炎功用的药物应用于PCOS患者,改善其炎性微环境,具有肯定的疗效。本文综述慢性炎症与PCOS的关系及相关研究进展。