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.     

Characterizing Standardized Functional Data at Inpatient Rehabilitation Facilities

ObjectiveThe Improving Medicare Post-Acute Care Transformation Act of 2014 mandates using standardized patient functional data across post-acute settings. This study characterized similarities and differences in clinician-observed scores of self-care and transfer items for the standardized section GG functional domain and the functional independent measure (FIM) at inpatient rehabilitation facilities.DesignWe conducted secondary analyses of 2017 Uniform Data System for Medical Rehabilitation national data. Patients were assessed by clinicians on both section GG and FIM at admission and discharge. We identified 7 self-care items and 6 transfer items in section GG conceptually equivalent with FIM. Clinician-assessed scores for each pair of items were examined using score distributions, Bland-Altman plot, correlation (Pearson coefficients), and agreement (kappa and weighted kappa) analyses.Setting and ParticipantsIn all, 408,491 patients were admitted to Uniform Data System for Medical Rehabilitation-affiliated inpatient rehabilitation facilities with one of the following impairments: stroke, brain dysfunction, neurologic condition, orthopedic disorders, and debility.MeasuresSection GG and FIM.ResultsPatients were scored as more functionally independent in section GG compared with FIM, but change score distributions and score orders within impairment groups were similar. Total scores in section GG had strong positive correlations (self-care: r = 0.87 and 0.95; transfer: r = 0.82 and 0.90 at admission and discharge, respectively) with total FIM scores. Weak to moderate ranking agreements with total FIM scores were observed (self-care: kappa = 0.49 and 0.60; transfers: kappa = 0.43 and 0.52 at admission and discharge, respectively). Lower agreements were observed for less able patients at admission and for higher ability patients of their change scores.Conclusions and ImplicationsOverall, response patterns were similar in section GG and FIM across impairments. However, variations exist in score distributions and ranking agreement. Future research should examine the use of GG codes to maintain effective care, outcomes, and unbiased reimbursement across post-acute settings.     

直肠癌新辅助放疗研究进展

在过去的近40年里，直肠癌的治疗方案逐渐标准化。大多数早期直肠癌患者仅通过手术即可得到充分的治疗。然而，相当比例的直肠癌患者处于局部进展期，此类患者需要行新辅助治疗。直肠癌的新辅助放射治疗已被证明能有效地降低患者术前肿瘤分期、改善患者生存以及降低直肠癌局部复发率等，随之而来的是患者放疗后出现的不同程度的放疗不良反应，但随着放射治疗规范化、放射治疗技术及设备的改进，放疗不良反应严重程度在逐渐降低。本文就新辅助放疗中的放疗方案的选择、放射治疗技术、放疗不良反应、放疗后的手术时间以及放疗后的观察与等待等问题的最新研究进展进行了系统性的综述，从而为临床直肠癌新辅助治疗提供有力依据。     

Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.     

Incidence and risk factors for Chyle leak after pancreatic surgery for cancer: A comprehensive systematic review

BackgroundChyle leak (CL) is a clinically relevant complication after pancreatectomy. Its incidence and the associated risk factors are ill defined, and various treatments options have been described. There is no consensus, however, regarding optimal management. The present study aims to systematically review the literature on CL after pancreatectomy.MethodsA systematic review from PubMed, Scopus and Embase database was performed. Studies using a clear definition for CL and published from January 2000 to January 2021 were included. The PRISMA guidelines were followed during all stages of this systematic review. The MINORS score was used to assess methodological quality.ResultsLiterature search found 361 reports, 99 of which were duplicates. The titles and abstracts of 262 articles were finally screened. The references from the remaining 181 articles were manually assessed. After the exclusions, 43 articles were thoroughly assessed. A total of 23 articles were ultimately included for this review. The number of patients varied from 54 to 3532. Incidence of post pancreatectomy CL varied from 1.3% to 22.1%. Main risk factors were the extent of the surgery and early oral or enteral feeding. CL dried up spontaneously or after conservative management within 14 days in 53% to 100% of the cases.ConclusionsThe extent of surgery is the most common predictor of risk of CL. Conservative treatment has been shown to be effective in most cases and can be considered the treatment of choice. We propose a management algorithm based on the current available evidence.