双环[1.1.1]戊烷衍生物的合成研究进展

双环[1.1.1]戊烷（BCP）是一种具有三维立体结构的桥环骨架，其作为苯环、叔丁基和炔烃的生物电子等排体，已经在药物化学领域得到广泛的应用。随着BCP应用范围的扩大，BCP及其衍生物的合成日益成为研究的热点。本文对BCP衍生物的主要合成策略和方法进行总结，旨在为新药研发人员提供参考。     

体外培育牛黄与天然牛黄指纹图谱的比较研究

目的：研究、比较体外培育牛黄与天然牛黄的指纹图谱。方法：利用TOFMS、HPIEJMS技术研究、比较体外培育牛黄与天然牛黄中肽类、胆汁酸类和胆红素类3类成分的指纹图谱。结果：体外培育牛黄与天然牛黄3类成分的指纹基本一致，但各成分间的相对含量有差异。结论：10批体外培育牛黄的指纹图谱有较好的一致性，说明体外培育牛黄的质量稳定。4批天然牛黄的指纹图谱，尤其是胆汁酸类成分的指纹图谱差异明显，说明天然牛黄由于来源不同，导致质量不够稳定.     

Comprehensive Care for Joint Replacement (CJR), a mandatory program with winners and losers

The Centers for Medicare and Medicaid (CMS) have continued to explore ways to decrease cost and increase quality in the provision of medical services. There is increasing concern that the current “fee-for-service” payment structure of American medicine may do neither. CMS has developed several programs aimed at incentivizing better quality at a lower spend, termed Alternative Payment Models (APMs). CJR is the largest, being implemented in 67 metropolitan regions. This is a mandated bundle payment where providers initially are not at risk, but hospitals control the bundle and are at risk. Clearly, in any program designed to curtail spending there will be losers and winners, “musical chairs” if you will. This article reviews the scope of services within the bundle, and predicts how specific stakeholders will do.     

双向冲水法在无肝素血液透析中的应用效果

目的探讨双向冲水法用于无肝素血液透析中对患者透析器及静脉壶凝血程度、透析时间的影响。方法选取2018年12月至2019年12月于医院行无肝素血液透析的62例患者,按随机数字表法分为两组,各31例。对照组予以传统冲水法,观察组予以双向冲水法,比较两组透析器及静脉壶凝血程度、透析时间。结果两组透析器凝血程度比较,差异无统计学意义(P>0.05);观察组静脉壶凝血程度低于对照组,差异有统计学意义(P<0.05);观察组透析时间长于对照组,差异有统计学意义(P<0.05)。结论双向冲水法可降低无肝素血液透析患者静脉壶凝血程度,延长透析时间,增强透析效果。     

Chance and challenge of associating liver partition and portal vein ligation for staged hepatectomy

BackgroundThe associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was first performed in 2007. The critical patient selection, timing to perform the second stage operation, and minimally invasive technique are three key factors for patient outcomes. The aim of this review is to summarize published data on these three aspects.Data sourcesStudies were identified by searching PubMed for articles published from January 2007 to October 2018, using the keywords “associating liver partition and portal vein ligation for staged hepatectomy” or “ALPPS” or “in situ split”. Studies on colorectal liver metastasis (CRLM), perihilar cholangiocarcinoma (PHC), and hepatocellular carcinoma (HCC) indicated for ALPPS, cutoff values to determine the timing of stage 2, as well as modifications of ALPPS were included.ResultsThe mortality of ALPPS for CRLM is declining, for PHC is high. In patients with HCC, essential hypertrophy makes the ALPPS safer. However, the degrees of fibrosis affect the hypertrophy. The future liver remnant volume is still the gold standard to start the second stage. Hepatobiliary scintigraphy plays an important role in quantitatively assessing liver function, whereas cutoff values need to be further calibrated. Less-invasive ALPPS modifications have increased and led to a decreased mortality.ConclusionsALLPS improved the CRLM outcomes; ALPPS is feasible in patients with PHC after failure of portal vein embolization; ALPPS may be an option for HCC patients with major vascular invasion and thrombosis. The simplified and less-invasive ALPPS is the trend.     

Sodium phenylbutyrate improved the clinical state in an adult patient with arginase 1 deficiency

An adult female patient was diagnosed with arginase 1 deficiency (ARG1-D) at 4 years of age, and had been managed with protein restriction combined with sodium benzoate therapy. Though the treatment was successful in ameliorating hyperammonemia, hyperargininemia persisted. After being under control with a strict restriction of dietary protein, severe fall of serum albumin levels appeared and her condition became strikingly worsened. However, after sodium phenylbutyrate (NaPB) therapy was initiated, the clinical condition and metabolic stability was greatly improved.Current management of ARG1-D is aimed at lowering plasma arginine levels. The nitrogen scavengers, such as NaPB can excrete the waste nitrogen not through the urea cycle but via the alternative pathway. The removal of nitrogen via alternative pathway lowers the flux of arginine in the urea cycle. Thereby, the clinical complications due to insufficient amount of protein intake can be prevented. Thus, NaPB therapy can be expected as a useful therapeutic option, particularly in patients with ARG1-D.     

SP联合CBL在骨外科临床实践教学中的应用研究

目的探讨标准化病人(standard patient,SP)结合案例式教学(case-based learning,CBL)在骨外科临床实践教学中的应用效果。方法选取2018—2019学年于我院骨科实习的南京医科大学2014级临床医学专业学生50人作为研究对象。随机将其均分为试验组和对照组两组,每组各25人。试验组采用SP+CBL相结合教学方法;对照组采用传统CBL授课方法。在教学结束后,请所有参与试验的学生对课程进行评价,并从理论和操作两方面对学生进行考核。结果两组学生的理论考试成绩无明显差异,不具统计学意义(P>0.05)。但试验组学生的临床技能操作考核成绩高于对照组(P<0.01)。试验组学生对SP+CBL教学在激发学习兴趣、增强解决实际问题能力及提高骨外科实践教学质量等方面的满意度显著高于对照组(P<0.01)。结论SP+CBL教学优于传统CBL教学,可以显著提高学习的积极性,有助于提高骨外科临床实践教学的效果。     

Activation status of CD56dim natural killer cells is associated with disease activity of patients with systemic lupus erythematosus

Clinical Rheumatology - Decreased natural killer (NK) cells have been reported in systemic lupus erythematosus (SLE) patients. However, the role of NK cells in the pathogenesis of SLE is not well...     

MYNN rs10936599基因多态性与急性心力衰竭患者短期预后的相关性

目的探讨MYNN基因的rs10936599位点多态性与急性心力衰竭（AHF）患者预后的关系。 方法选取2012年3月至2016年3月于南京医科大学第一附属医院心血管内科住院的AHF患者328例,采用TaqMan探针法对MYNN基因的SNP位点rs10936599（T/C）进行基因多态性检测,记录并比较不同基因型患者（TT基因型、CT基因型、CC基因型）住院期间的人口学特征、临床资料、病因和伴随疾病、住院期间治疗用药等基线资料,并对所有患者进行12个月的前瞻性随访,随访终点为全因死亡。分析rs10936599位点多态性对AHF预后的影响。 结果（1）rs10936599基因型频率分布：TT基因型100例（占30.5%）,CT基因型162例（占49.4%）,CC基因型66例（占20.1%）;rs10936599位点的基因型和等位基因频率在死亡患者和存活患者间比较,差异有统计学意义（χ²=9.749,P=0.0076;χ²=9.641,P=0.0019）。（2）心率、血清钾水平及住院期间地高辛和醛固酮拮抗剂使用情况在不同基因型患者间比较,差异有统计学意义（H=7.714,P=0.021;F=3.254,P=0.040）;其他基线资料在不同基因型患者间比较,差异无统计学意义（P＞0.05）。（3）Kaplan-Meier曲线分析显示携带等位基因C（CC/CT）的AHF患者12个月生存率较TT基因型患者明显下降,差异有统计学意义（TT vs CT,P=0.026;TT vs CC,P=0.002）。（4）进一步Cox回归分析结果显示杂合子CT基因型和纯合子CC基因型是影响AHF患者预后的独立危险因素（HR=2.10,95%CI：1.07~4.12;HR=2.96,95%CI：1.42~6.19）。 结论MYNN基因rs10936599位点多态性与AHF患者预后有关,CC和CT基因型是预测AHF患者12个月不良预后的独立危险因素。     

Fas信号通路通过诱导EMT促进胃癌细胞的侵袭转移

目的探讨Fas信号通路促进胃癌细胞侵袭转移的可能相关机制。方法以低浓度FasL处理胃癌细胞株AGS,免疫印迹及ELISA检测上皮间质转化(epithelial-mesenehymal transition,EMT)的分子生物学标记改变;稳定沉默Snail及Twist转录因子,transwell小室侵袭实验检测FasL处理后胃癌细胞的侵袭能力;免疫印迹检测信号通路激活状态及相应的抑制效应。结果 FasL可以诱导AGS细胞株出现EMT表型,并可促进胃癌细胞的侵袭转移能力。同时该过程中出现ERK1/2信号通路的激活,而抑制ERK1/2信号通路,可以抑制FasL诱导EMT及提高肿瘤侵袭能力的作用。胃癌组织中相应分子生物学标记的表达变化符合EMT的发生。结论 Fas信号通路能够激活ERK1/2通路诱导EMT的发生,并且能通过该机制增强胃癌细胞AGS的活动能力。