Whether or not use of intravenous alteplase in combination with endovascular thrombectomy (EVT) improves outcomes versus EVT alone, for acute stroke patients with large vessel occlusion presenting directly to a comprehensive stroke center, is uncertain. Six randomized trials and two clinical guidelines exploring this issue were published in 2021 and 2022. The European Stroke Organisation (ESO) published a guideline that made a strong recommendation in favor of intravenous thrombolysis plus EVT over EVT alone for acute stroke patients presenting with anterior circulation large vessel occlusion and who are eligible for both treatments, while our team guideline, a study-level meta-analysis and economic analysis of all six trials suggested proceeding with thrombectomy alone without intravenous alteplase. Here, we synthesized this evidence and discuss the difference between the two guidelines. In the future, more effective intravenous drug therapies are needed.
Ginsenoside Rg3 (Rg3), extracted from the root of Panax ginseng, is one of the most abundant ginsenosides. Rg3 exhibits anticancer activity in various cancer models in vitro and in vivo by modulating several signaling pathways, such as those of phosphatidylinositol 3-kinase, epidermal growth factor receptor, mitogen-activated protein kinases, p53, nuclear factor kappa-B, and reactive oxygen species. Besides, Rg3 can be used as adjunctive with conventional anticancer therapies, enhancing therapeutic effects and reversing drug resistance in cancer therapy. So, the purpose of this review is to provide a systematic summary and analysis the anticancer effects and the potential mechanisms of Rg3 extracted from ginseng.
Neonatal sepsis is divided into early-onset sepsis (EOS) and late-onset sepsis (LOS). The European neonatal detection network reported in 2011 that EOS has a high mortality rate of 26.3%, almost double that of LOS (13.3%). EOS sometimes lacks specific symptoms, which makes early diagnosis difficult and leads to extensive empirical antibiotic therapy with potential hazards and both immediate and long-term adverse outcomes. The Neonatal EOS Risk Calculator is an assessment model proposed in recent years to quantify the risk of EOS in newborns based on a range of high-risk factors in the perinatal period. This model has attracted widespread attention in some developed countries and has been applied in retrospective and prospective clinical studies, suggesting new strategies to address the appropriate use of antibiotics in neonates. This article reviews the clinical application and research progress of the Neonatal EOS Risk Calculator.
Background: The poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, olaparib has been approved for the treatment of mCRPC in patients with BRCA1/2 mutations who have progressed following prior therapy that included a new hormonal agents. Patients with prostate cancer carrying BRCA gene mutations exhibit a more aggressive disease progression and poorer prognosis, posing challenges for the effectiveness of current treatment options.
Methods: From the perspective of healthcare payers in China, a three-state partition survival model (progression-free survival, progressed disease and death) was constructed to conduct a cost-effectiveness analysis of olaparib versus enzalutamide for the approved indication. The efficacy and safety of olaparib and enzalutamide were obtained from PROfound trial. Cost were from pricing records and the literature. The model was simulated for 10 years with monthly cycles. Costs and health outcomes were discounted by 5%. Sensitivity analyses were conducted to evaluate the robustness of parameters on the results.
Results: In the base-case analysis, the total cost of olaparib was ¥ 101,012, with a total of 1.1576 QALYs gained. The total cost of enzalutamide was ¥ 52,425, with a total of 0.5929 QALYs gained. Compared to enzalutamide, olaparib had an ICER of ¥ 86,043 per QALY, with an increase in total costs of ¥ 48,587 and an increase in QALYs of 0.5647. At a threshold of three times per capita GDP of China (¥ 257,094 in 2022), the probability of olaparib being cost-effective compared to enzalutamide was 99.0%.
Conclusion: From the healthcare payer perspective, olaparib is cost-effective compared to enzalutamide for the treatment of metastatic castration-resistant prostate cancer in patients with BRCA1/2 mutations who have progressed following prior therapy that included a new hormonal agent.
The significant gap between animal experimentation and clinical trials has resulted in immense expenses in time and money in drug development. The popularity of researches on alternative models to animal experimentation has grown, with the development of artificial organs at its forefront. Three state-of-the-art technologies used to simulate organs are organ-on-a-chip, organoid, and 3D bioprinting. Organ-on-a-chip technology utilizes flexible fluidic manipulation and accurate recreation of the cell microenvironment. Organoid technology allows for the development of personalized mini-organs and the testing of drugs on different human species. 3D bioprinting technology is capable of creating artificial organs with intricate 3D structures. All these technologies play a significant role in developing drugs in highly efficient mode.
Antibody-based drugs have been a significant breakthrough in the field of cancer treatment in recent years with the development of biotechnology in pharmaceuticals. These drugs utilize artificially synthesized antibodies to target specific antigens on cancer cells for targeted therapy. Bispecific antibodies (BsAbs) and antibody–drug conjugates (ADCs) are emerging classes of antibody-based drugs. Currently, there are five approved BsAbs and fifteen approved ADCs globally for the treatment of various solid tumors and hematological malignancies. BsAbs can target two different antigens, allowing for more precise targeting, increased specificity, and reduced toxicity. ADCs consist of antibody, linker, and payload, offering improved efficacy and reduced side effects. This article provides an overview of approved BsAbs and ADCs globally, including their characteristics, therapeutic targets, indications, clinical efficacy, and safety profiles, aiming to provide insights into the global development of these types of drugs.
Objective: To explore the molecular mechanism of Banxia -Chenpi in the treatment of cough variant asthma with phlegm evil accumulation lung syndrome based on network pharmacology and molecular docking technology.
Methods: TCMSP database was used to screen the active ingredients and targets of Banxia-Chenpi. GeneCards, OMIM and PharmGKB databases were used to obtain the targets of cough variant asthma. Cytoscape 3.9.1 software was used to construct the “couplet medicines-active ingredients-targets” network and screen key ingredients according to the degree value. The protein–protein interaction data were obtained from the STRING database and core targets were screened by Cytoscape plugin cytoNCA. The core targets conduct GO and KEGG pathway enrichment analyses in the David database. Molecular docking technology was used to verify the binding energy between key ingredients and core targets.
Results: There were 16 active ingredients and potential 118 targets in Banxia-Chenpi,2429 cough variant asthma targets, and 72 intersection targets. The key ingredients of the Banxia-Chenpi in treating cough variant asthma were nobiletin, baicalein, naringenin, stigmasterol, beta-sitosterol and coniferin. The core targets of the Banxia-Chenpi for CVA treatment were FOS, MMP9, AKT1, CASP3, TP53, JUN and VEGFA. The molecular docking results indicated key ingredients and core targets of the Banxia-Chenpi in CVA treatment had a good binding affinity.
Conclusion: Active ingredients maybe act on MMP9, AKT1, VEGFR and FOS to reduce eosinophils and neutrophils accumulation, dissolve phlegm, alleviate airway inflammation, and reduce airway resistance and hyperresponsiveness for treating CVA. This study provides a reference for clinical medication and subsequent research.
Background: Huangqin-Jinyinhua couplet medicines (HQJYH) were often used to treat hand-foot and mouth disease (HFMD), although its mechanism remains unclear. This study investigated the active ingredients in HQJYH and their mechanism when treating HFMD by network pharmacology and molecular docking.
Methods: The TCMSP database obtained the principal active ingredients found in HQJYH. The GeneCards, CTD, PharmGkb and DisGeNet databases were used to obtain the main targets involved in HFMD, and the merged targets were obtained by R software and the Venn package. The DAVID database performed GO and KEGG enrichment analyses on the intersection targets. We also used Cytoscape software to construct an “HQJYH-Active Ingredients-Targets” network and used the STRING platform to conduct protein–protein interaction (PPI) analyses on the intersection targets. Molecular docking of core active ingredients-core targets interactions were modeled using AutoDock Vina software.
Results: 56 active ingredients were found in HQJYH, corresponding to 212 targets, 5323 HFMD targets, and 156 intersection targets. KEGG enrichment analysis found that genes were mainly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway and other pathways. Cytoscape showed that the core active ingredients were quercetin, luteolin, kaempferol, beta-sitosterol, stigmasterol, wogonin, baicalein and acacetin. The PPI network showed that the core targets involved were TP53, CASP3, AKT1, IL6, MAPK14, EGFR, and HIF1A. The molecular docking results indicated key binding activity between Baicalein-AKT1, quercetin-AKT1, wogonin-AKT1, kaempferol-AKT and wogonin-MAPK14.
Conclusion: This study was based on network pharmacology and revealed the potential molecular mechanisms involved in treating HFMD by HQJYH.