Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

Hcy、LPA及TGF-β1在创伤性骨折下肢静脉栓塞中的预测价值

目的分析同型半胱氨酸(Hcy)、溶血磷脂酸(LPA)及转化生长因子-β1(TGF-β1)在创伤性骨折下肢静脉栓塞中的预测价值。方法选取2019年3月至2020年2月商丘市第一人民医院收治的104例创伤性骨折者(观察组),根据有无DVT:有DVT组33例,无DVT组71例;根据创伤严重程度:轻度组61例,重度组43例。另选取本院同期92例健康体检者设为对照组。比较不同人群、不同病情程度以及有无DVT者血浆Hcy、LPA及血清TGF-β1水平,分析Hcy、LPA及TGF-β1对DVT的预测价值。结果观察组Hcy、LPA及TGF-β1表达水平均明显高于对照组,差异均有统计学意义(P<0.05)。重度组Hcy、LPA及TGF-β1表达水平明显高于轻度组,差异均有统计学意义(P<0.05)。有DVT组者Hcy、LPA及TGF-β1表达水平明显高于无DVT组,差异均有统计学意义(P<0.05)。依据ROC曲线分析可知,Hcy+LPA+TGF-β1三者联合预测创伤性骨折后发生DVT敏感度和特异度分别为88.90%、8130%,明显高于三者单独检测(P<0.05)。结论Hcy、LPA及TGF-β1在创伤性骨折发生下肢静脉栓塞时水平均明显升高,三者联合检测对下肢静脉栓塞早期诊断有重要的临床价值。     

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

靶向MLL1-WDR5蛋白-蛋白相互作用抑制剂的研究进展

Mixed lineage leukemia 1(MLL1)是组蛋白甲基转移酶SET家族的成员之一。MLL1与WDR5、RbBP5、Ash2L和DPY-30组成MLL1甲基转移酶复合物调控组蛋白H3的第4位赖氨酸的甲基化水平，对造血系统的发育和血细胞的更新至关重要。部分白血病患者体内存在因MLL1基因易位而产生的致癌蛋白——MLL1融合蛋白，MLL1融合蛋白在发挥其致癌作用时需要功能完整的MLL1酶复合物，故靶向MLL1-WDR5的蛋白-蛋白相互作用成为治疗MLL1融合型白血病的潜在策略。本文对MLL1-WDR5蛋白-蛋白相互作用的生物学机制、结构信息以及抑制剂进行了系统的总结，并结合已报道数据对该领域进行了展望，以期为后续研究提供参考。     

New approaches to moderate CRISPR-Cas9 activity: Addressing issues of cellular uptake and endosomal escape

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Deepm5C: A deep-learning-based hybrid framework for identifying human RNA N5-methylcytosine sites using a stacking strategy

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嘌呤能受体X1与肺腺癌预后及免疫细胞浸润的相关性研究

目的：探索嘌呤能受体X1(purinergic receptor，P2RX1)与肺腺癌(LUAD)患者预后及免疫细胞浸润的相关性。方法：利用生物信息学技术分析非小细胞肺癌中P2RX1的表达及其甲基化与患者预后的关系，对P2RX1共表达基因进行富集分析并筛选核心基因。利用TIMER 2.0数据库、R软件等分析P2RX1与免疫细胞、免疫检查点、免疫基质评分等的相关性。结果：P2RX1在LUAD中表达下调，低表达P2RX1的患者预后较差(P<0.05)，且P2RX1与肿瘤纯度、分期等临床病理因素有关(P<0.05)。P2RX1的表达与肺鳞癌患者预后无明显相关。Cg06475633等P2RX1 CpG位点甲基化与患者预后相关。P2RX1共表达基因主要富集于免疫细胞活化、分化等通路和生物学进程，核心基因主要包括BTK、IKZF1等。P2RX1的表达与B细胞浸润、免疫/基质评分、PD-1、CTLA-4等多个免疫检查点显著相关(P<0.05)。结论：P2RX1有望成为LUAD诊断和免疫治疗的新靶点。     

脂质纳米粒-mRNA递送系统及其在嵌合抗原受体T细胞治疗中的应用

尽管嵌合抗原受体（CAR）T细胞治疗在血液系统恶性肿瘤患者中取得了显著的临床疗效，但需要进一步优化。脂质纳米粒（LNP）-信使核糖核酸（mRNA）递送系统作为一种非病毒性基因载体运用于CAR-T细胞治疗研究中，一方面通过LNP将密封蛋白-6 mRNA靶向递送至抗原提呈细胞，从而实现抗原提呈细胞辅助性增强密封蛋白-6靶向的CAR-T细胞的功能，以进一步诱导对实体瘤的清除；另一方面，通过LNP将成纤维细胞激活蛋白（FAP）CARmRNA靶向递送至T细胞，实现体内FAP靶向的CAR-T细胞的制备，以通过阻断心脏纤维化过程达到治疗急性心肌损伤的目的。在CAR-T细胞研究和治疗中，LNP-mRNA递送系统具有不与细胞基因组整合、价格便宜、毒副作用小及可修饰等优点，亦存在蛋白瞬时表达导致调控细胞功能的持久性不足及制备等方面的技术局限性。本文综述了LNP-mRNA递送系统及其在CAR-T细胞治疗中的应用研究。