Design and synthesis of novel organometallic complexes using boronated phenylalanine derivatives as potential anticancer agents

Drug design and discovery studies are important because of the prevalence of diseases without available medical cures. New anticancer agents are particularly urgent because of the high mortality rate associated with cancer. A series of mononuclear gold (III) and platinum (II) complexes based on boronated phenylalanine (BPA) were designed and synthesized using 4,4’-dimethyl-2,2’-dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising anticancer drug candidates. Proton nuclear magnetic resonance, infrared, mass spectrometry, and elemental analyses were utilized for chemical characterizations. Cell viability, cancer cell colony formation, endothelial tube formation, and cytoskeleton staining assays were performed using A549 lung adenocarcinoma and human umbilical vein endothelial cells (HUVECs) to investigate preliminary pharmacological activities. L1-based platinum (II) complex (BPA-L1-Pt) was the most promising complex, and has similar activity with the approved chemotherapy drug cis-platinum. Half maximal inhibitory concentration values for BPA-L1-Pt were 9.15 µM on A549s and 16.61 µM on HUVECs; the values for cis-platinum were 5.24 µM on A549s and 23.14 µM on HUVECs. Consequently, further synthesis studies should be performed to boost the cancer cell selectivity feature of BPA by varying metal and ligand types.     

脂蛋白相关磷脂酶A2、胰岛素样生长因子-1与老年VD患者认知功能的关系及预测价值研究

目的 探讨脂蛋白相关磷脂酶A2（Lp-PLA2）、胰岛素样生长因子-1（IGF-1）与老年血管性痴呆（VD）患者认知功能的关系及预测价值。方法 选择2019 年3～6 月在我院接受治疗的VD 患者60 例为研究对象，同时选取同期在我院接受检查的健康者60 例为对照组，比较两组患者的Lp-PLA2、IGF-1、简易智力状态检查量表评分（MMSE）水平；采用Pearson 相关性分析法对Lp-PLA2、IGF-1 与MMSE 评分的相关性进行分析；采用受试者工作曲线（ROC）下面积（AUC）比较Lp-PLA2、IGF-1 对VD 的预测价值。结果 观察组患者的Lp-PLA2 水平明显高于对照组（P＜0.05），观察组患者的IGF-1、MMSE 评分明显低于对照组（P＜0.05）；Lp-PLA2 与MMSE 评分呈负相关性，IGF-1 与MMSE 评分呈正相关性；Lp-PLA2 与IGF-1 诊断VD 的AUC 值分别为0.940、0.954。结论Lp-PLA2 水平越低，IGF-1 水平越高，患者的认知功能越好，且Lp-PLA2、IGF-1 对老年VD 患者均具有较高的预测价值。     

Endoplasmic reticulum stress is involved in ventilator-induced lung injury in mice via the IRE1α-TRAF2-NF-κB pathway

Inflammation plays a critical role in the development of ventilator-induced lung injury (VILI). Endoplasmic reticulum (ER) stress is associated with a variety of diseases through the modulation of inflammatory responses. However, little is known about how ER stress is implicated in VILI. In this study, murine mechanical ventilation models were constructed. Total protein and inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF), and lung tissue injury was assessed by histology. Our data revealed that mice subjected to high tidal ventilation (TV) for 4 h showed more severe pulmonary edema and inflammation than those of mice with spontaneous breathing and low TV-treatment. In addition, the high TV-treated animals upregulated the ER stress markers GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB expression at both the mRNA and protein levels in lung tissue. Administration of thapsigargin exacerbated the histological changes, inflammation and expression of GRP78 and CHOP after high TV, but treatment with ER stress and IRE1α kinase inhibitors attenuated the pathological damage and downregulated the high expression of GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB, suggesting that ER stress is involved in VILI though the IRE1α/TRAF2/NF-κB signaling pathway in mice.     

Glycopolymer Code: Programming Synthetic Macromolecules for Biological Targeting

Targeting in a cellular level is still one of the major challenges in biomedical treatments. However, new synthetic and analytical techniques now allow the development of precisely prepared macromolecules. Thus, glycopolymer chains are reported to be prepared with controlled length, monomer sequences, as well as chain‐folded structures. A high level of complexity in synthetic macromolecules also allows increased selectivity in targeting, which is a key factor in biomedical applications.     

附加钢板技术治疗股骨干髓内钉术后骨不连的现状和研究进展

目的对附加钢板技术治疗股骨干髓内钉术后骨不连的历史、现状和进展进行综述。方法广泛查阅国内外关于附加钢板技术治疗股骨干髓内钉术后骨不连的临床研究文献，并进行综合分析。结果自 1997 年附加钢板技术已成功用于治疗股骨干髓内钉术后骨不连，根据原髓内钉是否失效，可分为保留原髓内钉和更换原髓内钉两类。该技术不仅适用于简单骨不连，还可用于合并严重畸形的复杂性骨不连。相比更换髓内钉、更换外侧钢板和双钢板技术，附加钢板技术手术创伤更小，骨折愈合时间更短，骨折愈合率更高，患者能更早重返社会和工作。然而，该技术也存在一些问题有待解决，包括双皮质螺钉固定困难、缺乏适合股骨干解剖型附加钢板以及缺乏术后功能和生活质量的评估研究。结论相比其他翻修固定方式，附加钢板技术能够获得更高的骨折愈合率和更好的临床预后。然而，术后患者能否在功能和生活质量方面进一步获益还有待证实。此外，还需要更高质量的临床对照研究深入证明其是否确实优于其他翻修固定方式。     

Perioperative management of diabetes

Diabetes is a complex, chronic metabolic disorder affecting approximately 9.3% of the adult population with the estimated number of adults with diabetes worldwide having more than tripled since 2000. This increase has largely been attributed to global urbanization and lifestyle changes. Diabetes affects 10–15% of the surgical population. These patients are frequently elderly, have complex medical co-morbidities and present for both high-risk elective and emergency surgery. This multisystem disease poses a significant challenge to both anaesthesia and surgery with patients with diabetes demonstrating higher morbidity and mortality rates compared to their non-diabetic counterparts. It is crucial that good glycaemic control is maintained throughout the perioperative period as this has been shown to correlate with positive patient outcomes. It is well-recognized that a co-ordinated, multidisciplinary approach aimed at optimizing every point in the patient pathway from GP referral to post-discharge care is required to obtain the best outcomes for the surgical patient with diabetes. The anaesthetist has a key role in the perioperative diabetes multidisciplinary team. Patients themselves are well experienced in manging their own diabetes and should be involved in doing so whenever possible.     

Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma

Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings.