血清miR-155联合组织PTEN检测对子宫内膜癌的诊断价值

目的 探讨血清微小RNA-155(miR-155)联合组织人第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)检测对子宫内膜癌的诊断价值。方法 选取2015年9月至2018年6月邯郸市第一医院妇产科收治的子宫内膜癌51例、良性病变患者52例,采用荧光实时定量聚合酶链反应(Q-PCR)法检测研究对象血清中miR-155表达,免疫组织化学法检测各组子宫内膜组织中PTEN水平,并通过受试者工作特征(ROC)曲线评价miR-155、PTEN及二者联合对子宫内膜癌的诊断价值。结果 与良性病变组相比,子宫内膜癌组血清miR-155表达水平显著升高,差异有统计学意义(P<0.05);与良性病变组相比,子宫内膜癌组PTEN蛋白表达量显著降低,差异有统计学意义(P<0.05);ROC曲线显示,血清miR-155水平预测患者子宫内膜癌发生的曲线下面积为0.876,灵敏度为96.3%,特异度为94.2%;子宫内组织PTEN水平预测患者子宫内膜癌发生的曲线下面积为0.952,灵敏度为94.1%,特异性度为92.3%;二者联合检测诊断子宫内膜癌曲线下面积为0.991,灵敏度为99.2%,特异度为92.5%。结论 血清miR-155联合组织PTEN检测可作为子宫内膜癌的诊断指标。     

Establishing a prognostic model for metachronous second squamous cell lung cancer in patients with resected squamous cell lung cancer

BackgroundFor metachronous second pulmonary squamous cell carcinoma (msPSC) in patients with resected PSC, the method to distinguish tumour clonality has not yet been well established, which makes it difficult to determine accurate staging and predict prognosis.MethodsPatients who underwent surgery for first PSC and encountered msPSC were recruited from the Surveillance, Epidemiology, and End Results (SEER) database. We extracted overall survival 1 (OS1) for the first PSC, overall survival 2 (OS2) for msPSC, and interval survival for the time interval between the first and second PSC. The nomogram was calibrated for OS2, and recursive partitioning analysis (RPA) was performed for risk stratification.ResultsA total of 617 patients were identified. Several independent prognostic factors were identified and integrated into the nomogram for OS2, including gender, age (2^nd), nodal status (1^st), node metastasis (2^nd), and extrapulmonary metastasis (2^nd). The calibration curves showed optimal agreement between the predictions and actual observations, and the c-index was 0.678. Surgery was associated with longer survival for msPSC patients. The prognosis of sublobectomy was comparable and inferior to that of lobectomy in the low- and moderate-risk groups, respectively. Radiotherapy was associated with better outcomes in patients who did not undergo surgery.ConclusionsThe RPA-based clinical nomogram appears to be suitable for the prognostic prediction and risk stratification of OS2 in msPSC. This practical system may help clinicians make decisions and design clinical studies.     

内关穴双向调节作用考略

[目的]归纳内关穴对多病症的双向调节作用。[方法]采集古代文献,整理出内关穴定位、主治症及相关配穴处方的原文,按病症进行分析归纳。[结果]通过本次文献研究,证明了内关穴对心肺、脾胃、大肠小肠、女子胞宫等脏腑的病症有双向调节作用。[结论]内关穴有多项双向调节作用。     

引导式教育理念在脑瘫儿童康复护理中的应用

目的:探讨引导式教育理念在脑瘫儿童康复护理中应用的可行性和疗效。方法 :选择2015年7月—2016年12月在深圳市儿童医院康复科接受康复护理的120例脑瘫患儿,随机分为研究组(60例)和对照组(60例)。对照组采用常规康复护理方法,研究组采用基于引导式教育理念的康复护理方法。分别在初诊时和治疗结束后24周时采用粗大运动功能评估量表(Gross Motor Function Measure,GMFM)对患儿进行评估,比较2组患儿的康复疗效。结果 :2组患儿治疗结束后24周时的GMFM能区评分均较初诊时显著提高(P值均0.05),并且研究组的评分(84.37±5.94)显著高于对照组(68.77±6.02)(P0.05)。研究组的总有效率(86.7%,52/60)亦显著高于对照组(68.3%,41/60)(P0.05)。结论 :将引导式教育理念引入脑瘫儿童的康复护理中能够显著提高康复治疗的效果,值得在临床上予以推广应用。     

脂质代谢相关新基因与肝肿瘤发生研究进展

研究发现,恶性肿瘤存在基因异常和代谢异常,后者表现在能量代谢的异常较突出,而作为肿瘤能量来源底物的脂肪酸代谢研究并不多见。本文讨论了与脂质代谢相关的新基因,如ALDOC、TUBB5、ANXA2、FABP4、ApoA1和AOP1,CIDE家族蛋白（Cidea、Cideb、Fsp27）,在产生癌症相关性恶病质中起关键作用的脂肪甘油三酯脂肪酶（ATGL）和激素敏感性脂肪酶（HSL）,长链酰基辅酶A脱氢酶（ACADL）,SCD1、FASN或ACC1等。由于肿瘤细胞与正常细胞在能量代谢上存在明显的差异,因此根据这种区别以能量代谢途径上的某个分子作为肿瘤治疗的靶点是完全有可能的。     

志愿者同伴教育在慢性阻塞性肺疾病病人健康教育中的应用

[目的]探讨志愿者同伴教育在慢性阻塞性肺疾病(COPD)病人健康教育中的应用。[方法]将70例COPD病人采用随机数字表法分为观察组和对照组各35例,对照组采用常规健康教育,观察组在常规健康教育基础上应用志愿者同伴教育,比较干预前后两组病人健康教育对病情的改善情况。[结果]观察组病人干预后戒烟、家庭氧疗、呼吸功能训练干预、心理干预等方面优于对照组,差异有统计学意义(P0.05)。[结论]志愿者同伴教育可帮助COPD病人提高自护行为能力,是COPD病人健康教育的有益方式。     

A mild and concise synthesis of aryloxy phosphoramidate prodrug of alcohols via transesterification reaction

A synthesis of aryloxy phosphoramidate prodrug of alcohols enabled by a transesterification strategy is described here. This reaction operates under mild conditions and thus has excellent functional group tolerance. This method provides an efficient and practical solution to the rapid construction of the aryloxy phosphoramidate prodrugs library for potential SAR studies.

A synthesis of aryloxy phosphoramidate prodrug of alcohols enabled by a transesterification strategy is described here.

The phosphate and phosphonate prodrug strategy is widely recognized as an effective approach to improve the physicochemical and pharmacological properties of therapeutic nucleosides and sugars.¹ Over the last few decades, the ProTide prodrug strategy pioneered by Prof. Chris McGuigan has emerged as a powerful platform for developing nucleotide therapeutics.² This prodrug approach has been extensively studied in the antiviral and anticancer fields, enabling the discovery and development of three FDA-approved antiviral drugs and several clinical candidates (Fig. 1a).³ Whereas early efforts focused mainly on nucleoside-based medicines, many recent discoveries suggested that this technology can be applied to non-nucleoside substrates as well.⁴ The nature of different components of the phosphoramidate core is essential for the prodrug''s potency, especially for the case of non-nucleoside drug candidates in which other amino acid motifs are more effective than the commonly used l-alanine.⁵ As a result, SAR studies of amino acid ester and aryl moieties would be necessary to identify the optimal combination of these masking groups when applying ProTide technology to a new therapeutic chemical entity. Consequently, an efficient method capable of rapidly assembling aryloxy phosphoramidate prodrug library from parent drug would be very attractive to the discovery of new ProTide prodrugs.Open in a separate windowFig. 1Pharmaceutical importance and the synthetic methods of aryloxy phosphoramidate prodrugs.Current methods for the preparation of aryloxy phosphoramidate structures include: (a) phosphorylating the nucleoside with phosphorochloridate reagent,⁶ (b) ester exchange between nucleoside and a diarylphosphite followed by oxidative amination,⁷ (c) coupling of the amino acid ester with a nucleoside aryl phosphate or its derivatives.⁸ Among these methods, coupling nucleosides with phosphorochloridate reagents in the presence of either N-methylimidazole (NMI) or tert-butyl magnesium chloride (tBuMgCl) is the most popular strategy for ProTide prodrug construction (Fig. 1b). Although this method has enabled the synthesis of numerous nucleoside prodrugs, regioselectivity and diastereoselectivity issues associated with this approach remained challenging.⁹ As a result, numerous efforts have been devoted to develop methods with high regioselectivity¹⁰ and diastereoselectivity.¹¹ While these advances offer a variety of choices on batch synthesis of designated compounds, other issues remain to be addressed. First, the current method mainly focused on accessing phosphoramidate prodrugs containing l-alanine and nucleoside. The compatibility of these methods towards other amino acid motif and non-nucleosides substrates are less investigated. Second, compatible substrate nucleoside bases are limited due to the high reactivity of phosphorylating reagents such as phosphorchloridate or diarylphosphite, which have to involve protection of the nucleobase moiety sometimes.Given the growing interest in expanding ProTide technology to other therapeutic areas and the unmet need for rapid access to the prodrug library for hit screenings or SAR studies, we wonder if we can develop a practical method capable of preparing aryloxy phosphoramidates prodrugs from both nucleoside and non-nucleoside substrates. We reasoned that N-diphenyl phosphoryl amino acid ester could serve as a mild phosphorylating reagent and afford aryloxy phosphoramidate prodrugs via a simple transesterification process. Herein, we report our discovery on a DBU promoted synthesis of aryloxy phosphoramidates prodrugs from stable and readily available N-diphenylphosphoryl amino acid esters and alcoholic substrates (Fig. 1c).We began our study by examining the reaction of phosphoramidate 1 and stavudine (d4T, anti-HIV drug) in the presence of diisopropylethylamine (DIPEA) as the base in acetonitrile (CH₃CN) at 25 °C (12 Increasing the equivalents of phosphorylating reagent 1 to 2.0 equivalent or 3.0 equivalent afforded the target product in 91% and 92% yield, respectively (entries 5–6). Stoichiometry optimization on base revealed that 2.0 equivalent of DBU was optimal, with 1.0 or 3.0 equivalent of DBU gave impaired yield (entries 7–8). In addition, solvent is proved to be vital for a productive reaction, as replacing CH₃CN with DCM, DMF, and THF only afford product 3 in 27% to 71% yield (entries 9–11). To test the scalability of this strategy, we conducted a 1.5 mmol scale synthesis of product 3 under the standard conditions. This reaction afforded the desired product in 85% isolated yield, demonstrating the scalability and potential synthetic application of this protocol.¹³Optimization of the reaction conditions^a

经导管纽扣式堵塞装置关闭小儿室间隔缺损临床探讨

目的为探讨经导管纽扣式堵塞装置关闭小儿室间隔缺损的疗效。方法我科从1995年1月～1997年9月采用Sideris纽扣式补片关闭小儿室间隔缺损9例。结果堵闭成功8例，失败1例，经1月～2年随访，4例恢复良好，2例有轻或中度主动脉瓣关闭不全，1例残余分流2．smm，1例中度三尖瓣关闭不全。结论本方法关闭小儿室间隔缺损，从指征，堵塞装置及操作技术上尚待进一步研究。