基于文本挖掘和生物医学数据库的新型冠状病毒肺炎药物发现

目的 基于文本挖掘技术和生物医学数据库对新型冠状病毒肺炎（COVID-19）相关文献进行数据挖掘分析，探究COVID-19及其主要症状发热、咳嗽、呼吸障碍相关基因靶点，筛选潜在有效的化学药和中药。方法 使用GenCLiP 3网站获取COVID-19和其主要症状咳嗽、发热、呼吸障碍共4个关键词的共有靶点，在METASCAPE数据库中对其进行基因本体（GO）和通路富集分析，再利用String数据库和Cytoscape软件构建共有靶点的蛋白质相互作用网络，筛选获得核心基因，运用DGIdb数据库、SymMap数据库针对核心基因进行中西医治疗药物预测。结果 获得COVID-19及其主要症状共有基因靶点28个，其中有IL2、IL1B、CCL2等核心基因16个，使用DGIdb数据库筛选获得与16个关键靶点相互作用的化学药包括沙利度胺、来氟米特、环孢素等28种，中药包括虎杖、黄芪、芦荟等70味。结论 COVID-19及其主要症状的病理机制可能和CD4、KNG1、VEGFA等28个共有基因相关，可能通过介导TNF、IL-17等信号通路参与COVID-19病理过程。潜在有效药物可能通过作用相关靶点通路起到治疗COVID-19的作用。     

Medication Adherence App for Food Pantry Clients With Diabetes: A Feasibility Study

Low-income food pantry clients are unable to adhere to the diet and physical activity recommendations of the American Diabetes Association. The aim of the study is to test the feasibility of using a mobile phone app to improve diabetes medication adherence. Clients with uncontrolled type 2 diabetes were enrolled in a mobile phone app featuring 70 days of text message reminders and incentives. The app and the 4-item Morisky Medication Adherence Scale evaluated medication adherence. Clinically significant medication adherence of 93% was achieved with use of the app. Phone app use is feasible among urban low-income clients to improve medication adherence.     

The gap between legal rules and practice in advertising non-registered pharmaceutical products : A new method of analysis

The market of non-registered pharmaceutical products is growing fast in number and overall costs, not only in the Netherlands, but also in other European countries. These products often give the impression that the consumer may expect 'an effect as from a drug'. Legally, there is a clear distinction between 'drugs' and 'commodities' in the Netherlands; the question is whether legislation and practice concur. In an investigation we analysed texts of advertisements for non-registered pharmaceutical products published in a popular magazine. A method was developed, based on the legal definition of a drug and jurisprudence, to determine in a qualitative and quantitative way the application of medicinal claims. It transpired that in 65% of the analysed advertisements explicit or implicit claims were made. These products should therefore be subject to drugs legislation. Thus, in the Netherlands there is a gap between legislation and practice in advertising non-registered pharmaceutical products.     

Deleterious effects of low-dose oestrogen theraphy on coronary status in patients with prostatic cancer

The effects of oestrogen therapy and of orchidectomy on coronarystauts, as reflected by exercise ECG-testing before and afteryear of tretment, were assessed in a randomized study of patients(N=100) prostatic cancer. Oestrogen was given as polyestradiolphosphate 80 mg i.m. per month in combination with 150 µgor in pre-traetment exercise test results Twelve months afterstart of therapy the oestrogen group showed a significantlygreater depression of the ST-segment during maximal exercisein leads CH₂ (P<0.0005) and CH⁵)P<0.01) compared withthe pre-treatment depression. Twenty-five per cent (N=13) ofthe patients in the oestrogen group suffered cardiovascularcomplications during the yera the of therapy, whereas no suchcomplications were observed in the orchidectomy group. However,even the patients in the oestrogen group who had not sufferedcardiovascular complications had significantly greater depressionsof the ST-segment during exercise both in lead CH₂ (P<0.0005)and in CH₅ (P<0.05). There was no significant change in theST-segment level in the orchidectomy group twelve months aftersurgery. In summary, we found of an induction of myocardialishaemia during treatment with exogenous oestrogens at low dosagein patients with prostatic. This deleterious effect of oestrogenon the coronary status argues against oestrogen therapy, sinceoedtrogen has not been shown to be more beneficial than orhidectomyagainst prostatic carcinoma.     

溶栓通脉胶囊纤溶活性和毒性的实验研究

目的:探讨溶栓通脉胶囊的纤溶性和毒性。方法:应用纤维蛋白平板法和纤维蛋白加热平板法对溶栓通脉胶囊的纤溶活性进行实验性研究;同时进行急性毒性试验。结果与结论:溶栓通脉胶囊具有很强的纤溶性且安全、无毒副作用。     

Effects of FR173657, a non-peptide B2 antagonist,on kinin-induced hypotension,visceral and peripheral oedema formation and bronchoconstriction

1. Kinins are believed to play a key role in many inflammatory conditions. Therefore, bradykinin antagonists are being developed for potential therapeutic applications. In the present investigation we describe the pharmacology, in vivo, of (E)-3-(6- acetamido- 3-pyridyl)- N-[N- [2,4- dichloro- 3-[(2- methyl-8- quinolinyl)oxymethyl]phenyl]- N-methylaminocarbonylmethyl]acrylamide ({"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657), a novel, non-peptide bradykinin antagonist.
2. The hypotensive effects of i.v. injections of bradykinin (50 pmol) in captopril-pre-treated anaesthetized rats were significantly inhibited by 100 nmol kg⁻¹ {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 s.c., and completely abolished by 300 nmol kg⁻¹. The full inhibitory effect developed within 60 min and remained unchanged for at least 4 h. However, the effect was reversible, since 24 h after an injection of 300 nmol kg⁻¹ {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 no inhibitory effect could be observed.
3. The plasma protein extravasation into the pancreas and duodenum induced by an i.v. infusion of bradykinin (11 nmol kg⁻¹ within 20 min) in captopril-treated anaesthetized rats was completely abolished by {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 at doses of 30 nmol kg⁻¹ s.c. and above, given 60 min before bradykinin. {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 3 nmol kg⁻¹ was ineffective, while a dose of 10 nmol kg⁻¹ produced an intermediate effect.
4. The paw oedema induced by the subplantar injection of bradykinin (30 nmol) in anaesthetized rats was inhibited slightly by s.c. injection of {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 0.3 μmol kg⁻¹, whereas 1 and 3 μmol kg⁻¹ produced significant inhibition of the bradykinin-induced oedema. The maximum inhibition amounted to about 50% and could not be increased even when the dose of {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 was increased to 30 μmol kg⁻¹. {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 did not effect the oedema caused by histamine or 5-hydroxytryptamine.
5. Bradykinin (20 nmol kg⁻¹, i.v.) caused increases in pulmonary inflation pressure by 300–600 Pa in anaesthetized, respirated guinea-pigs. The effect was reduced to 58±9% of the initial value 60 min after the s.c. injection of {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 1 μmol kg⁻¹, whereas only 9±7% remained after 10 μmol kg⁻¹. The bronchoconstrictor actions of histamine remained unaffected by {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657.
6. In summary, {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 is a highly potent and selective bradykinin antagonist. The inhibitory action in vivo lasts for longer than 4 h but is fully reversible. {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657, or similar compounds, will be a useful tool for the pharmacological investigation of pathophysiological states and may possess a therapeutic potential in diseases involving the endogenous release of kinins.

     

Increases in synthetic cannabinoids-related harms: Results from a longitudinal web-based content analysis

BackgroundSynthetic Cannabinoid Receptor Agonists (SCRA), also known as “K2” or “Spice,” have drawn considerable attention due to their potential of abuse and harmful consequences. More research is needed to understand user experiences of SCRA-related effects. We use semi-automated information processing techniques through eDrugTrends platform to examine SCRA-related effects and their variations through a longitudinal content analysis of web-forum data.MethodEnglish language posts from three drug-focused web-forums were extracted and analyzed between January 1st 2008 and September 30th 2015. Search terms are based on the Drug Use Ontology (DAO) created for this study (189 SCRA-related and 501 effect-related terms). EDrugTrends NLP-based text processing tools were used to extract posts mentioning SCRA and their effects. Generalized linear regression was used to fit restricted cubic spline functions of time to test whether the proportion of drug-related posts that mention SCRA (and no other drug) and the proportion of these “SCRA-only” posts that mention SCRA effects have changed over time, with an adjustment for multiple testing.Results19,052 SCRA-related posts (Bluelight (n = 2782), Forum A (n = 3882), and Forum B (n = 12,388)) posted by 2543 international users were extracted. The most frequently mentioned effects were “getting high” (44.0%), “hallucinations” (10.8%), and “anxiety” (10.2%). The frequency of SCRA-only posts declined steadily over the study period. The proportions of SCRA-only posts mentioning positive effects (e.g., “High” and “Euphoria”) steadily decreased, while the proportions of SCRA-only posts mentioning negative effects (e.g., “Anxiety,” ‘Nausea,” “Overdose”) increased over the same period.ConclusionThis study’s findings indicate that the proportion of negative effects mentioned in web forum posts and linked to SCRA has increased over time, suggesting that recent generations of SCRA generate more harms. This is also one of the first studies to conduct automated content analysis of web forum data related to illicit drug use.