Application of network pharmacology and molecular docking to elucidate the potential mechanism of Astragalus–Scorpion against prostate cancer

The present study aimed to investigate the molecular mechanism of the Astragalus–Scorpion drug pair in the treatment of prostate cancer (PCa). We employed network pharmacology and molecular docking technology to retrieving the active ingredients and corresponding targets of Astragalus–Scorpion by using TCMSP, BATMAN-TCM, TCMID and Swiss Target Prediction Databases. The targets related to PCa were retrieved through GeneCards. Cytoscape software was used to construct the ‘active ingredient–target disease’ network, and GO and KEGG enrichment analyses were performed on the common targets. Autodock software was used for molecular docking verification. In total, 26 active ingredients, 340 potential targets related to active ingredients and 122 common targets were screened from Astragalus–Scorpion drug pair. The core targets of the protein–protein interaction (PPI) network were JUN, AKT1, IL6, MAPK1 and RELA, whereas the core active ingredients were quercetin, kaempferol, formononetin, 7-o-methylisomucronulatol and calycosin. Nearly 762 GO entries and 154 pathways were obtained by using the pathway enrichment analysis. Molecular docking results revealed that quercetin and kaempferol bind to AKT1 and formononetin binds to RELA, all of which were found to be stable bounds.     

Research trends of prostatitis over past 20 years: A bibliometric analysis

In the past two decades, thousands of documents in the field of prostatitis have been published. This bibliometric analysis aimed to assess the characteristics, hotspots and frontiers trend of global scientific output on prostatitis. With the trend of moderate growth, altogether 2,423 papers were reviewed. The leading role of the United States in global prostatitis research was obvious, while China had developed rapidly in recent years. Queen's University and JOURNAL OF UROLOGY were the most prolific affiliation and journal respectively. Nickel, J. C made the greatest contribution to the field of prostatitis. Five hotspots have been confirmed: (a) male infertility associated with prostatitis and the molecular mechanisms; (b) diagnosis and treatment of prostatitis; (c) inflammation, pain and bladder irritation symptoms; (d) relationship between chronic prostatitis/chronic pelvic pain syndrome, benign prostatic hyperplasia and prostate cancer; (e) epidemiology, complications of prostatitis and improvement of acupuncture. This bibliometric analysis reveals that the international cooperation was becoming more and more close. Hotspot analysis shows that the molecular mechanism of prostatitis will be a hotspot in the future, mainly focussing on inflammatory immunity and oxidative stress.     

中药复方发明专利创造性审查的影响因素分析

目的 寻找中药复方发明专利创造性审查的关键影响因素并分析原因,为完善相关审查标准提供参考。方法 筛选驳回依据为创造性的中药复方发明专利复审决定,建立数据库,通过分类和单因素逻辑（Logistic）回归等方法分析影响因素。结果 中药复方专利创造性的审查标准受年度变化的影响明显。按要求补充实验数据、区别技术特征数量、复方的发明类型、审查员所引用的对比文件及公知常识情况均能提高专利复审的撤驳率。结论 我国尚未建立合理、统一、清晰的中药复方发明专利创造性审查标准,仍有待从多个方面进一步完善。     

基于UHPLC-QTOF-MS/MS和分子对接筛选紫菀中润肠通便的效应

目的 通过UHPLC-QTOF-MS/MS和分子对接技术阐明紫菀Aster tataricus中润肠通便作用的效应成分。方法 采用UHPLC-QTOF-MS/MS技术分析体内肠道内容物的成分,再利用SYBYL-X 2.0与Discovery Studio 4.0分子对接软件研究肠道内容物成分与M2受体、M3受体、蛋白激酶C(protein kinase C,PKC)蛋白的相互作用,明确各成分与靶标蛋白的结合强度。结果 体内肠道内容物中共鉴定出28个紫菀中的化学成分,有10个成分均可与M2受体、M3受体及PKC蛋白分子对接较好,其中astin J与3种靶标蛋白结合的平均打分值最高,这些成分均以非共价键方式与靶标蛋白结合,产生氢键、范德华力、经典作用力等相互作用。结论 紫菀中的astin J、asterin F、asterin A、异绿原酸A、异绿原酸B、异绿原酸C、绿原酸、槲皮素、山柰酚和木犀草素共10个成分可能是通过调节M受体及其下游信号通路PKC蛋白的表达发挥润肠通便的作用。     

基于网络药理学探究防风中生物活性成分及对类风湿关节炎的作用机制

目的 通过以网络药理学为基础的策略研究防风治疗类风湿关节炎（rheumatoid arthritis,RA）的分子生物学机制。方法 采用网络药理学方法收集防风活性成分和治疗RA的潜在靶点,并评估活性成分的药理和毒理学等相关参数;构建蛋白质相互作用网络筛选核心靶点,并通过生物信息学方法进一步验证核心靶点和疾病的关联;对核心成分和相应靶点进行分子对接。体外通过CCK-8实验、细胞迁移和侵袭、细胞凋亡、qRT-PCR和Western blotting分析,阐明别欧前胡素对MH7A细胞磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase,PI3K）/蛋白激酶B（protein kinase B,Akt）通路的调控作用。结果 从防风中共鉴定出18种活性成分和66个与筛选出的RA疾病靶基因相交的潜在靶基因,最终获得了汉黄芩素、β-谷甾醇、5-O-甲基维斯阿米醇和别欧前胡素等核心成分。防风治疗RA的潜在机制可能是通过调控PI3K/Akt、白细胞介素-17（interleukin-17,IL-17）、凋亡等信号通路和多种生物过程来实现,以发挥抗炎和免疫调节作用。分子对接证实了所有的核心成分和关键靶点均具有很好的对接活性。别欧前胡素抑制MH7A细胞的活力、迁移和侵袭（P＜0.05、0.01）,诱导细胞凋亡（P＜0.01）,并显著下调IL-1β、IL-6、IL-8、基质金属蛋白酶-1（matrix metalloproteinase-1,MMP-1）和MMP-3的基因表达（P＜0.01）。分子分析表明别欧前胡素通过抑制PI3K/Akt通路发挥对MH7A的调控作用。结论 成功预测了防风治疗RA的有效成分和潜在靶点,为进一步探究其分子机制提供了新的理论基础。揭示了别欧前胡素通过PI3K/Akt通路抑制RA成纤维样滑膜细胞的活力、迁移、侵袭及细胞因子和MMPs的表达,并诱导细胞凋亡。     

Guidelines for the diagnosis,treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases.     

海藻酸钙/枸杞多糖凝胶微球对小鼠骨质疏松的作用研究

目的研究海藻酸钙(ALG-Ca)/枸杞多糖(LBPs)凝胶微球对小鼠骨质疏松的作用。方法采用静电液滴法制备ALG-Ca凝胶微球、ALG-Ca/LBPs凝胶微球,用扫描电镜观察微球结构。建立去卵巢小鼠骨质疏松模型,随机分为假手术组、模型组、单纯ALG-Ca微球组、单纯LBPs组、ALG-Ca/LBPs凝胶微球组,每组8只,每日灌胃1次,干预时间为12周,对各组小鼠股骨行HE染色观察骨组织形态变化,Micro-CT检测并经三维重建获得骨组织微观结构,对小鼠血清骨钙素(BGP)、血清碱性磷酸酶(BALP)、1型胶原羧基末端肽(CTX-1)进行检测。结果扫描电镜观察示凝胶微球呈均匀一致的微球形结构;OVX+LBPs、OVX+ALG-Ca/LBPs组的BGP、BALP、CTX-1均低于OVX+PBS组(P<0.05);OVX+LBPs、OVX+ALG-Ca/LBPs组骨体积分数(BV/TV)、骨小梁数目(Tb.N)及骨小梁厚度(Tb.Th)均高于OVX+PBS组(P<0.05),骨小梁间隙(Tb.Sp)小于OVX+PBS组(P<0.05),以OVX+ALG-Ca/LBPs组为最佳(P<0.01)。结论ALG-Ca凝胶微球是LBPs治疗骨质疏松的良好药物缓释载体;LBPs为天然植物成分,通过LBPs/ALG-Ca凝胶微球可以改善骨质疏松小鼠的骨代谢及骨微结构。     

牛磺酸治疗通过激活自噬介导对老年大鼠骨量和骨强度的保护作用

目的探讨牛磺酸(NHS)对老年大鼠骨量流失的影响,并探讨可能的机制。方法将30只大鼠随机分为对照组(CON)、模型组(MOD)以及牛磺酸组(NHS),每组10只;其中NHS组大鼠每天接受牛磺酸(2 g/kg)治疗12周;待治疗结束后通过Micro-CT检测、HE染色切片、血清指标、蛋白质印迹观察治疗效果,探讨可能的机制。结果治疗12周后,与MOD组相比,三点弯曲试验、Micro-CT和HE染色切片结果显示NHS组大鼠的骨小梁数量、骨强度和骨密度(bone mineral density,BMD)得到明显改善。NHS组大鼠最大载荷和弹性模量、BMD、TV/BV、Tb.N、Tb.Th和Tb.Sp较OVX组明显改善(P<0.05)。和MOD组比较,NHS治疗后大鼠血清BLAP、P1NP、TRACP-5b和β-CTX水平明显降低,组间差异有统计学意义(P<0.05)。和MOD组比较,NHS组Runx2、BMP2、Beclin-1和LC3Ⅱ/LC3-Ⅰ表达水平明显上调,而P62表达水平显著下调,比较差异有统计学意义(P<0.05)。结论NHS可能通过激活自噬,从而对年龄引起的骨量丢失起到保护作用。     

生信分析肾阴虚型绝经后骨质疏松症分子机制及熟地黄靶向治疗

目的基于生信数据挖掘探究肾阴虚型绝经后骨质疏松症的病理机制及熟地黄的治疗靶点。方法通过GEO数据库挖掘阴虚型绝经后骨质疏松症患者差异表达基因,运用GeneCards及OMIM数据库预测骨质疏松症相关基因,采用R软件对阴虚靶点与骨质疏松靶点映射匹配。借助String数据库在线平台进行蛋白互作网络构建。分子对接预测熟地黄治疗阴虚型骨质疏松症的靶点。采用DAVID数据库进行生物过程及通路注释。结果通过分析得到差异表达基因1 272个,骨质疏松症靶点662个,阴虚型骨质疏松症相关靶点45个,主要涉及细胞凋亡调节、雌激素应答、骨骼肌系统发育等生物过程,并由PI3K-Akt、Wnt信号通路、MAPK信号通路、卵巢类固醇生成等信号通路调节。熟地2种有效成分能够作用于核心蛋白IGF1、VEGFA等。结论熟地黄可能靶向IGF1、VEGFA等核心蛋白,通过PI3K-Akt、MAPK等信号通路调节细胞凋亡及雌激素应答过程,从而实现防治阴虚型骨质疏松症的疗效。     

Incidence and risk factors of suicide among patients diagnosed with bladder cancer: A systematic review and meta-analysis

Background: Patients with bladder cancer have a high risk of suicide. This study aimed to assess how bladder cancer increases suicide risk and to identify the demographic and clinical factors associated with suicidal death among patients with bladder cancer. Methods: Literature search of MEDLINE, PsycINFO, Embase, Web of Sciences and Cochrane Library databases was conducted up to April 2020 to identify eligible studies related to the incidence and risk factors of suicide after bladder cancer diagnosis. Summary multivariate-adjusted risk estimates and their associated 95% confidence intervals (CIs) were calculated using inverse variance method with random or fixed-effect modeling. Results: Five retrospective cohorts comprising 563,680 patients with bladder cancer were included. Higher risk of suicide by 1.90-fold was observed among patients with bladder cancer (hazard ratio, HR = 1.90, 95% CI: 1.29–2.81; P = 0.001; I² = 81.2%), especially in those aged 70 years or older (HR = 1.36, 95% CI: 1.29–1.43; P < 0.001; I² = 0%), unmarried (HR = 1.72, 95% CI: 1.61–1.83; P < 0.001; I² = 0%), and those with regional bladder cancer (HR = 1.88, 95% CI: 1.10–3.21; P = 0.021; I² = 96.3%), compared with those without bladder cancer. Furthermore, gender and race were not associated with increased suicide risk among patients with bladder cancer. Conclusions: Suicide risk is increased among patients with bladder cancer, particularly those aged 70 years or older, unmarried and those with regional bladder cancer. Hence, early psychological support must be provided during the follow-up period of these special populations with a high suicide risk.