Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

Management of sagittal craniosynostosis: morphological comparison of eight surgical techniques

The aim of this study was to carry out a retrospective multicentre study comparing the morphological outcome of 8 techniques used for the management of sagittal synostosis versus a large cohort of control patients. Computed tomographic (CT) images were obtained from children CT-scanned for non-craniosynostosis related events (n = 241) and SS patients at preoperative and postoperative follow-up stages (n = 101). No significant difference in morphological outcomes was observed between the techniques considered in this study. However, the majority of techniques showed a tendency for relapse. Further, the more invasive procedures at older ages seem to lead to larger intracranial volume compared to less invasive techniques at younger ages. This study can be a first step towards future multicentre studies, comparing surgical results and offering a possibility for objective benchmarking of outcomes between methods and centres.     

Ventilatory support in the intensive care unit

This article focuses on the functional features of positive-pressure ventilators, the modes of invasive and non-invasive mechanical ventilation, and the main ventilator settings. It also highlights the potential complications of mechanical ventilation, the basic principles of weaning, and the pathophysiological basis of patient-ventilator dyssynchrony.     

Is routine extubation overnight safe in cardiac surgery patients?

Objectives

Expedient extubation after cardiac surgery has been associated with improved outcomes, leading to postoperative extubation frequently during overnight hours. However, recent evidence in a mixed medical-surgical intensive care unit population demonstrated worse outcomes with overnight extubation. This study investigated the impact of overnight extubation in a statewide, multicenter Society of Thoracic Surgeons database.

3D-CRT 低剂量区 V5体积的大小对非小细胞肺癌患者肺功能的影响

目的：探讨3D-CRT 低剂量区 V5体积的大小对非小细胞肺癌患者肺功能的影响。方法：收集我院肿瘤科2014年4月～2015年10月收治的46例首次行三维适形放射治疗且顺利完成治疗的非小细胞肺癌患者，对每例患者分别在治疗前以及治疗后的1、3个月进行肺功能检测，分析3D-CRT 低剂量区 V5体积的大小与肺功能变化之间的关系。结果：放疗后1个月的 FEV1％、FVC％值明显高于放疗前且差异均具有显著性。放疗后1个月、3个月的 DLCO％值明显低于放疗前，且放疗前的与放疗后3个月的差异具有显著性；V5≦45％、45％55％三组放疗前后的 FEV1％值和 FVC％值比较差异均不具有显著性。V5≦45％、45％55％三组放疗前后的 DLCO％值均呈逐渐下降趋势，且 V5>55％组的放疗前后 DLCO％值比较差异具有显著性。而 V5≦45％组和45％55％时，DLCO％值降低的趋势更加显著。     

Prostatic Artery Embolization—Anatomic Predictors of Technical Outcomes

PurposeTo determine if cone-beam CT and digital subtraction angiography analysis of pelvic arterial anatomy has predictive value for radiation exposure and technical success of prostatic artery embolization (PAE).Materials and MethodsThis prospective, nonrandomized, single-center study included 104 consecutive patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia. Cone-beam CT was performed in 160/208 (76.9%) hemipelves to determine prostatic artery (PA) origin. Classification of pelvic arterial tortuosity was possible in 73/104 (70.2%) patients. Learning curves of 2 interventionalists who performed 86.5% of PAEs were analyzed.ResultsTortuosity of pelvic arteries was classified as mild in 25 (34.2%) patients median age 64 years, moderate in 40 (54.8%) patients median age 69 years, and severe in 8 (11.0%) patients median age 70 years (mild vs moderate, P = .002; mild vs severe, P = .019); median fluoroscopy times were 24, 36, and 46 minutes (P = .008, P = .023); median contrast volumes were 105, 122.5, and 142 mL (P = .029, P = .064); and bilateral PAE rates were 84.0%, 77.5%, and 62.5% (P = .437), respectively. PA origin from superior vesical artery was most frequent (27.5%) and showed higher dose area product (median 402.4 vs 218 Gy ∙ cm², P = .033) and fluoroscopy time (median 42.5 vs 27 min, P = .01) compared with PA origin from obturator artery, which was least frequent. Interventionalist experience revealed significant impact on procedure times (median 159 vs 130 min, P = .006).ConclusionsTortuosity of pelvic arteries was more frequent in older patients and predicted worse technical outcomes of PAE. PA origin from obturator artery was associated with lower dose area product and fluoroscopy time, especially compared with PA origin from superior vesical artery. Interventionalist experience showed significant influence on technical outcome.     

Modern theatre design and usage: do joint replacements need laminar flow?

Since the introduction of laminar flow to theatre systems by Charnley, it has become a necessity in arthroplasty surgery. His initial work in the 1960s and 70s created improvements in terms of reducing overall rates of periprosthetic joint replacement, but it has been hard to ascertain if this stems from the laminar flow itself or improvements in asepsis and the utilization of perioperative antibiotics. The aim of this paper is therefore to establish if laminar flow is still a necessary addition to modern theatre design, particularly in joint replacement surgery, irrespective of other surgical factors. A wide variety of studies were utilized to form an objective analysis of whether laminar flow is essential to asepsis in theatre design. It explores a number of smaller earlier studies and ends with two large trials which provide evidence that laminar flow may in fact have a deleterious effect on the potential for peri-prosthetic joint infection (PJI). The article discusses potential reasons for these findings and seeks to explain them in context of overall asepsis during joint replacement surgery.