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.     

Trends in using mesenchymal stromal/stem cells (MSCs) in treating corneal diseases

Since their inception in the 1960s–70s, mesenchymal stem/stromal cells (MSCs) have gained interest because of their differentiation potential, anti-inflammatory effects, and immune-modulating properties. Both cell-based and cell-free MSC treatments show healing capacity in injured tissues. Cell-based treatment comprises MSCs and all secreted products, whereas cell-free treatments include only the secreted products. MSCs are therapeutically administered to many damaged organs owing to their efficacy. Specifically, the eye is a unique organ system to study the effects of MSCs, as treatment is easily applied and measured owing to its external location. The eye holds an immune-privileged status, wherein inflammation and immune responses are innately down-regulated. As excessive inflammation in the cornea often leads to fibrosis and irreversible corneal hazing, many studies have investigated the anti-inflammatory and immune-modulating capacities of MSCs. Decades of research suggest that MSCs modulate the immune response by secreting cytokines, growth factors, and extracellular matrix proteins that inhibit the infiltration of inflammatory cells following injury and promote a healing phenotype via M2 macrophage polarization. MSCs have also shown trans-differentiation potential into cornea-specific cell types during the wound healing process, such as corneal epithelial, stromal, or endothelial cells. This review discusses recent investigations of MSC treatment in the cornea, focusing on therapeutic efficacy, mechanisms, and future directions.     

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。     

儿童1型糖尿病骨密度变化及影响因素分析

目的 测定儿童1型糖尿病(T1DM)患者骨密度(BMD),分析探讨骨密度变化的影响因素。方法 选取于2018年1月—2021年6月于我院收治的儿童1型糖尿病患者76例,收集性别、年龄、发病年龄、身高、体重、BMI、病程等基本资料,检测空腹血糖、空腹C肽、糖化血红蛋白(HbA1c)、血碳酸氢根(HCO3-)、血清碱性磷酸酶(ALP),应用双能X线吸收测定法测定骨密度,获取Z值。结果 76例儿童1型糖尿病患者骨密度Z值为-0.93±2.14。HbA1c、病程与骨密度Z值呈负相关,差异具有统计学意义(分别B=-0.334,P<0.001;B=-0.191,P=0.017)。结论 儿童1型糖尿病患者骨密度低于健康儿童,血糖控制不良、病程长是1型糖尿病儿童骨密度减低的危险因素。     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.     

上调miR-145表达抑制卵巢癌HO8910细胞侵袭、迁移及促进TβR-Ⅱ蛋白表达北大核心

目的:探究微小RNA-145(microRNA-145,miR-145)对卵巢癌(ovarian cancer, OC)HO8910细胞侵袭、迁移及TβR-Ⅱ蛋白水平的影响。方法:将某大学研究实验室细胞库提供的OC细胞HO8910分为ZW组(无转染HO8910细胞)、ZN组(转染miR-145-NC)、YJ组(转染miR-145 mimics)。采用qRT-PCR、MTT、Hoechst33258荧光染色、Transwell小室、细胞划痕、Western blot检测miR-145、转化生长因子βⅡ型受体(transforming growth factorβtypeⅡreceptor, TβR-Ⅱ)表达、细胞活力、凋亡、侵袭、迁移能力以及TβR-Ⅱ蛋白量。结果:YJ组HO8910细胞中miR-145的表达量最高,提示转染成功。YJ组TβR-Ⅱ表达量较其他两组对比明显提高(P<0.05),ZW组、ZN组miR-145、TβR-ⅡmRNA表达水平无明显差异(P>0.05);培养48、72、96 h, YJ组细胞活力较ZW组、ZN组比较明显减弱(P<0.05),随着时间的延续,培养96 h三组细胞活力均优于48、72 h(P<0.05);YJ组与ZW组、ZN组对比细胞凋亡率明显提高(P<0.05);ZW组HO8910细胞荧光强度最弱,细胞凋亡率最低,ZW组与ZN组对比无明显差异(P>0.05);三组细胞侵袭、迁移数量相比差异较大(P<0.05),其中YJ组侵袭、迁移数量少于其他两组(均P<0.05),ZN组与ZW组的细胞侵袭、迁移数量无明显差异(P> 0.05);YJ组TβR-Ⅱ蛋白表达量与ZU组、ZN组对比明显升高(P<0.05),YJ组转化生长因子-β(transforming growth factorβ,TGF-β)蛋白表达量与其他两组对比均降低(P<0.05),ZW组TGF-β、TβR-Ⅱ蛋白表达量与ZN组对比差异较小(P> 0.05)。结论:通过上调miR-145对抑制OC细胞迁移、侵袭等生物活性发挥积极作用,分析原因可能与靶向调控TβR-Ⅱ蛋白相关。