Inhibition of phosphodiesterase-4 suppresses HMGB1/RAGE signaling pathway and NLRP3 inflammasome activation in mice exposed to chronic unpredictable mild stress

Inhibition of phosphodiesterase-4 (PDE4) produces robust anti-inflammatory and antidepressant-like effects in multiple animal models. However, the detailed mechanisms have not been well studied. Receptor for advanced glycation endproducts (RAGE) and inflammasome activation are implicated in the etiology of depression. Here, we aimed to investigate the involvement of RAGE and nucleotide-binding domain (NOD)–like receptor protein 3 (NLRP3) inflammasome in the antidepressant-like effects of PDE4 inhibition in mice. We found that inhibition of PDE4 by roflupram (ROF, 0.5, and 1.0 mg/kg, i.g.) exerted antidepressant-like effects in mice subjected to chronic unpredictable mild stress (CUMS). Simultaneously, ROF inhibited CUMS-induced microglial activation and restored the morphology of microglial cells in the hippocampus, as evidenced by reduced total process length, area, volume, number of branching points, number of terminal points and total sholl intersections of microglia. ROF also decreased the expression of ionized calcium-binding adapter molecule-1 and the level of interleukin-1β. Western blot analysis showed that PDE4 inhibition suppressed the high-mobility group box 1 protein (HMGB1)/RAGE signaling pathway, as the levels of HMGB1, RAGE, toll-like receptor 4, phosphorylated p38 mitogen-activated protein kinase, and nuclear factor κ-B were decreased in both hippocampus and cortex in mice after treatment with ROF. Moreover, ROF also attenuated the protein levels of NLRP3, the apoptosis-associated speck-like protein containing (ASC), and cysteine-requiring aspartate protease-1 (Caspase-1), which are key proteins in the NLRP3-mediated inflammasome signaling pathway. In summary, these results demonstrate that the down-regulation of HMGB1/RAGE signaling pathway and inflammasome suppression possibly contribute to the antidepressant-like effects of PDE4 inhibitors. And, ROF has potential as a candidate drug in the treatment of depression.     

CT-based radiomics nomogram for preoperative prediction of No.10 lymph nodes metastasis in advanced proximal gastric cancer

IntroductionPreoperative diagnosis of No.10 lymph nodes (LNs) metastases in advanced proximal gastric cancer (APGC) patients remains a challenge. The aim of this study was to develop a CT-based radiomics nomogram for identification of No.10 LNs status in APGCs.Materials and methodsA total of 515 patients with primary APGCs were retrospectively selected and divided into a training cohort (n = 340) and a validation cohort (n = 175). Total incidence of No.10 LNM was 12.4% (64/515). CT based radiomics nomogram combining with radiomic signature calculated from venous CT imaging features and CT-defined No.10 LNs status evaluated by radiologists was built and tested to predict the No.10 LNs status in APGCs.ResultsCT based radiomics nomogram yielded classification accuracy with areas under ROC curves, AUC = 0.896 and 0.814 in training and validation cohort, respectively, while radiomic signature and radiologist’ diagnosis based on contrast-enhanced CT images yielded lower AUCs ranging in 0.742–0.866 and 0.619–0.685, respectively. In the specificity higher than 80%, the sensitivity of using radiomics nomogram, radiomic signature and radiologists’ evaluation to detect No.10 LNs positive cases was 82.8% (53/64), 67.2% (43/64) and 39.1% (25/64), respectively.ConclusionsThe CT-based radiomics nomogram provides a promising and more effective method to yield high accuracy in identification of No.10 LNs metastases in APGC patients.     

Preoperative Enteral Nutritional Support in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma: A Strengthening the Reporting of Observational Studies in Epidemiology Article

To compare the short-term outcomes between hepatocellular carcinoma (HCC) patients with and those without preoperative nutrition on the basis of postoperative enteral nutrition.HCC patients with postoperative enteral nutrition who underwent liver resection between February 2010 and December 2014 in Nanjing Drum Tower Hospital were considered for the study: 43 patients with and 36 patients without preoperative nutrition. Primary endpoint was the incidence of overall complications. Secondary endpoints were infectious and major complications.In the preoperative enteral nutrition group, shorter length of postoperative hospital stay (10.5 ± 2.7 versus 13.7 ± 6.3 days, P = 0.007), less exogenous albumin infusion (10.2 ± 22.4 versus 47.8 ± 97.7 g, P = 0.030), earlier first exhaust time (2.7 ± 0.8 versus 3.0 ± 0.9 days, P = 0.043), and first defection time (3.5 ± 0.9 versus 4.4 ± 1.4 days, P = 0.001) were observed. No significant differences were observed in the incidence of overall complications (32.6% versus 52.8%, P = 0.070), infectious complications (7.0% versus 8.3%, P = 1), and major complications (14.0% versus 11.1%, P = 0.969) between the preoperative enteral nutrition and control group.Preoperative enteral nutrition could improve short-term outcomes of HCC patients via accelerating the recovery of gastrointestinal function and shortening the length of postoperative hospital stay.     

围术期血容量变化对异丙酚代谢动力学影响的研究概况

血容量的变化不仅引起血流动力学的相应改变,也将导致机体内环境的变化,如血浆蛋白浓度的改变,这些变化都将影响药物在体内的转运和代谢,特别是高蛋白结合及高肝摄取药物,如异丙酚,从而影响药物疗效和（或）增加不良反应的发生。本文综述了近年来有关围术期血容量变化对异丙酚代谢影响的研究,以期有助于临床合理用药。     

1例房颤患者服用华法林期间INR值异常波动的药学监护

1例78岁房颤患者长期服用华法林,1NR值控制在1．6～2．5。入院当日测PT41．6S,INR3．53,遂停用华法林。4d后测INR1．25,低于正常水平,患者重新口服华法林。因关节疼痛加用塞来昔布,监测凝血四项显示PT、INR值分别由14．4S、1．25上升至36．7S、3．12。临床药师分析患者所用药物中,氯雷他定、塞来昔布均可加强华法林的抗凝作用,建议停用华法林、静脉注射维生素K1,医师采纳。此后,继续监测患者的凝血指标,至INR值回落后恢复使用华法林。患者住院期间未发生出血及栓塞事件。