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.     

2035年中国入围科技期刊“世界第一方阵”:基础、差距与推进思路

【目的】 在“中国科技期刊卓越行动计划”实施三周年之际,有必要对我国科技期刊2035年迈入“世界第一方阵”目标的具体任务进行重新审视和预判,以进一步明确发展方向,动态调整推进思路。【方法】 采用国内外科技期刊、科技论文、科技期刊评价成果的系统性发展数据对科技期刊“世界第一方阵” 国家(或地区)在高水平科技期刊数量与质量层面的入围标准进行界定,在深入总结现有基础和优势的同时,对我国科技期刊综合实力与“世界第一方阵”国家(或地区)的现实差距进行逐一梳理和剖析,并对实现目标的可行性和推进思路进行研判和设计。【结果】 必须继续加强高水平英文科技期刊创办和培育力度、持续加大优秀中文科技期刊的建设强度、快速推进国内外科技期刊论文等质同效评价制度的建设与引导,并积极探索建立科学家和科研机构办好一流科技期刊的责任制度和贡献激励机制、创新发展编辑人才队伍培养与激励管理思路、深入实践灵活多样的期刊出版市场资本运作模式、稳步推进期刊出版市场机制和管理制度改革,为我国科技期刊事业的高质量发展提速增效。【结论】 虽然当前阶段目标任务艰巨,但迈入“世界第一方阵”未来可期。     

Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings

We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted.     

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.     

SLC及其受体CCR7与Ⅰ期非小细胞肺癌淋巴结微转移的相关性

目的 探讨溶质载体蛋白（SLC）及其受体趋化因子受体7（CCR7）与I期非小细胞肺癌（NSCLC）淋巴结微转移的相关性。方法 选取2019年1月~2020年3月于我院就诊的I期NSCLC患者127例为研究对象，按照淋巴结微转移情况分为对照组92例和转移组35例，所有患者入院后均通过根治术切除病灶，通过免疫组化方式检测病灶中SLC7A11及CCR7含量，并收集患者临床资料、实验室检查资料及影像学检查资料。通过Logistic回归分析评价SLC7A11及CCR7与淋巴结微转移之间的关系。最后通过建立ROC曲线分析两者及其联合检测对NSCLC患者微淋巴结转移的预测价值。结果 两组患者SLC7A11及CCR7表达水平存在显著差异（P＜0.05）。转移组患者病灶直径、支气管受累及TLG显著高于对照组（P＜0.05）。病灶直径（OR=49.254,95%CI=11.062~507.604）是影响NSCLC淋巴结微转移的独立危险因素（P＜0.05）。SLC7A11（OR=8.622）及CCR7（OR=8.709）表达水平是影响NSCLC淋巴结微转移的独立因素（P＜0.05）。SLC7A11、CCR7及联合诊断对NSCLC淋巴结微转移具有较好的检测价值（均P＜0.05）。联合检测特异度显著高于 SLC7A11及CCR7单独检测（2=7.292，15.125；均P＜0.01）。结论 SLC家族的中SLC7A11及其受体CCR7与NSCLC患者微淋巴结转移显著相关。     

Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

腹腔镜胆囊切除术治疗急性结石性胆囊炎的疗效

目的探讨分析对急性结石性胆囊炎患者采用腹腔镜胆囊切除术进行治疗的临床效果,以及对患者的胃肠功能和C反应蛋白所造成的影响。方法本次研究对象乃是我院肝胆外科于2017年4月-2019年4月期间收治的急性结石性胆囊炎患者62例,按照患者就诊的先后顺序对其进行平均分组,比较两组患者的术后肠鸣音恢复时间、肛门排气时间、排便时间、C反应蛋白水平以及并发症发生率。结果腹腔镜手术组患者的术后肠鸣音恢复时间(13.6±3.5)小时、肛门排气时间(16.5±2.7)小时以及排便时间(25.7±3.3)小时,均明显少于开腹式手术组患者(P<0.05);腹腔镜手术组患者的术后并发症发生率(6.45%)明显低于开腹式手术组患者(25.80%)(P<0.05);腹腔镜手术组患者的C反应蛋白水平为(10.4±2.5)mg/L,少于开腹式手术组患者(P<0.05)。结论根据本次研究的结果可以确认,对急性结石性胆囊炎患者采用腹腔镜胆囊切除术进行治疗能够取得更好的效果,可以促使患者的胃肠功能在术后更快的恢复,提高患者的C反应蛋白,从而有效避免患者出现并发症。     

新生儿肺炎PCT和炎性因子水平表达及其意义

目的研究新生儿肺炎(NP)患儿血清高敏C反应蛋白(hs-CRP)、降钙素原(PCT)、白细胞介素-6(IL-6)水平表达及其意义。方法选取2017年1月-2018年2月韶关市曲江区妇幼保健计划生育服务中心诊治的NP患儿80例,按细菌感染情况分为观察1组和观察2组,各40例。选择同期40例健康新生儿作为对照组。测定并比较三组的hs-CRP、PCT和IL-6水平。结果观察1组血清PCT、hs-CRP和IL-6水平明显高于观察2组和对照组,差异均有统计学意义(P<0.05)。观察1组血清PCT、hs-CRP和1L-6检测阳性率明显高于观察2组和对照组,差异均有统计学意义(P<0.05),且观察1组血清PCT、hs-CRP和1L-6诊断NP的敏感度均明显高于观察2组,差异均有统计学意义(P<0.05);观察组各指标特异度与观察2组比较差异无统计学意义(P>0.05)。结论血清hs-CRP、PCT、IL-6水平可作为NP患儿的辅助鉴别指标,为抗生素的合理使用和疗效提供依据。     

组织气氛在护士知识与行为间的中介效应:以脑卒中吞咽障碍护理为例

目的探究组织气氛在护士吞咽障碍知识水平与护理行为之间的中介效应。方法2019年6-7月,便利抽样法选取15个省市33所医院及医疗机构神经科、康复科具有吞咽障碍护理经验的231名护士为研究对象采用脑卒中吞咽障碍知识水平问卷、脑卒中吞咽障碍护理行为问卷及团队创新气氛量表对其进行调查。结果护士吞咽障碍知识水平总分为(56.69±13.50)分、护理行为得分为(140.65土32.02)分、组织气氛得分为(157.63±26.56)分。组织气氛与吞咽障碍知识水平(r=0.49,P<0.01)、护理行为(r=0.50,P<0.01)均呈正相关。组织气氛在知识水平和护理行为之间起中介作用,中介效应占总效应的83.18%。结论组织气氛在护士吞咽障碍知识水平与护理行为之间起中介作用,临床管理者可在提升护士吞咽障碍知识水平的基础上,通过提高组织气氛水平推进其护理行为。