There is a need to understand the relationship between COVID-19 Convalescent Plasma (CCP) anti-SARS-CoV-2 IgG levels and clinical outcomes to optimize CCP use. This study aims to evaluate the relationship between recipient baseline clinical status, clinical outcomes, and CCP antibody levels.
To evaluate the effectiveness and safety of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) undergoing complex percutaneous coronary intervention (PCI).It remains inconclusive whether ticagrelor is superior to clopidogrel in ACS patients undergoing complex PCI in real-world practice.Based on an all-comers PCI registry, we compared the long-term effectiveness and safety between ticagrelor and clopidogrel in ACS patients undergoing complex PCI, defined as PCI procedures for complex lesions including bifurcation, chronic total occlusion, ostial, tortuous, calcific, diffused, thrombus-containing, and restenotic lesions. The primary ischemic outcome was a composite of cardiac death, myocardial infarction, or stroke. The safety outcome comprised Bleeding Academic Research Consortium (BARC) types 2, 3, and 5 bleeding. Propensity score matching (PSM) was performed to reduce bias.Among ACS patients who underwent complex PCI, 4373 (35.2%) and 8065 (64.8%) received dual antiplatelet therapy based on ticagrelor and clopidogrel, respectively. The incidences of composite ischemic events (before PSM: 1.74% vs. 2.84%; after PSM: 1.50% vs. 2.65%; p < 0.01 for both) and all-cause death (before PSM: 1.23% vs. 2.12%, p < 0.01; after PSM: 1.09% vs. 1.81%, p = 0.02) were significantly lower in the ticagrelor-treated than in the clopidogrel-treated group. There was no significant difference in BARC types 2, 3, and 5 bleeding between groups.Whilst the risk of major bleeding was comparable between the two drugs, ticagrelor was associated with a significantly lower risk of ischemic events than clopidogrel in ACS patients undergoing complex PCI.
Background. There are few studies comparing recurrences between endoscopic retrograde cholangiopancreatography (ERCP) and open choledochotomy (OCT). Aims. To compare the effect of different surgical methods on single and multiple recurrences of choledocholithiasis. Methods. A total of 1255 patients with choledocholithiasis who underwent ERCP or OCT were retrospectively studied. The recurrence of choledocholithiasis was calculated by the Kaplan–Meier method with the log-rank test. Multivariate analyses of recurrent choledocholithiasis were performed by introducing variables with in univariate analysis into the logistic regression model. Results. A total of 204 (16.7%, 204/1225) patients relapsed. Among the 204 patients, 74.5% relapsed within three years after surgery, of whom 39.7% (81/204) had multiple relapses (≥ 2). The recurrence rate of ERCP (17.2%, 119/692) was higher than that of OCT (15.1%, 85/563), but the difference was not statistically significant. The independent risk factors for a single recurrence of choledocholithiasis were diabetes, stone , maximum stone , sedentary occupation, the approach of ERCP (EST or EPBD), periampullary diverticulum, primary suture, high-fat diet (postoperative), frequency of weekly vegetable intake (< 4, postoperative), and drinking (postoperative). However, the ERCP approach (EST or EPBD), OCT approach (LCBDE), primary suture, high-fat diet (postoperative), and frequency of weekly vegetable intake (< 4, postoperative) were independent risk factors for multiple recurrences of choledocholithiasis. Conclusion. Patients with choledocholithiasis should be followed up regularly for one to three years after treatment. Stone number ≥ 2, diabetes mellitus, periampullary diverticulum, surgical methods, and lifestyle are all risk factors for the recurrence of choledocholithiasis. ERCP is still the preferred surgical method based on the advantages of low risk of cholangitis recurrence, less hospital stay, minimally invasive surgery, fewer postoperative complications, and easier acceptance by elderly patients. In addition to optimizing the treatment plans, postoperative lifestyle management is also vital.
Abstract Background Postoperative pulmonary embolism (PE) is a severe complication leading to death and poor prognosis. The present study investigated the risk factors and potential predictors of PE in cancer patients undergoing thoracic and abdominopelvic surgery. Methods A retrospective study was conducted on the patients with cancer who underwent thoracic and abdominopelvic surgery in Sichuan Cancer Hospital from December 2016 to January 2022. A total of 189 patients were included, in which 63 patients diagnosed PE after operation were collected as PE group, and 126 patients matched by age, type of cancer and cancer location were enrolled as control group. Conditional logistic regression was conducted to analyze the association between PE and risk factors. Predictive values of key factors were compared by the area under the curve (AUC) in receiver operating characteristic curve (ROC) curve. Results Conditional multivariate logistic regression showed that BMI (odds ratio [OR] 4.065, 95% confidence interval [CI] 1.138–14.527; p = 0.031), intraoperative hypotension time (OR 4.095, 95% CI 1.367–12.266; p = 0.009), same day fluid balance (OR 0.245, 95% CI 0.061–0.684; p = 0.048), and postoperative D-Dimer (OR 1.693, 95% CI 1.098–2.611; p = 0.017) were significantly related to the occurrence of postoperative PE. Postoperative D-Dimer had the maximal AUC value 0.8014 (95% CI: 0.7260–0.8770) for predicting PE, with a cutoff value of 1.505 μg/ml. Conclusions BMI, intraoperative hypotension time, lower same day fluid balance and postoperative D-dimer are independent risk factors associated with PE in cancer patients undergoing thoracic and abdominopelvic surgery. Postoperative D-Dimer seems to be a good indicator to predict postoperative PE for cancer patients.
Schistosomiasis is a tropical disease that poses a significant risk to hundreds of millions of people, yet often goes unnoticed. While praziquantel, a widely used anti-schistosome drug, has a low cost and a high cure rate, it has several drawbacks. These include ineffectiveness against schistosome larvae, reduced efficacy in young children, and emerging drug resistance. Discovering new and active anti-schistosome small molecules is therefore critical, but this process presents the challenge of low accuracy in computer-aided methods. To address this issue, we proposed GNN-DDAS, a novel deep learning framework based on graph neural networks (GNN), designed for drug discovery to identify active anti-schistosome (DDAS) small molecules. Initially, a multi-layer perceptron was used to derive sequence features from various representations of small molecule SMILES. Next, GNN was employed to extract structural features from molecular graphs. Finally, the extracted sequence and structural features were then concatenated and fed into a fully connected network to predict active anti-schistosome small molecules. Experimental results showed that GNN-DDAS exhibited superior performance compared to the benchmark methods on both benchmark and real-world application datasets. Additionally, the use of GNNExplainer model allowed us to analyze the key substructure features of small molecules, providing insight into the effectiveness of GNN-DDAS. Overall, GNN-DDAS provided a promising solution for discovering new and active anti-schistosome small molecules.
Focused ultrasound (FUS) combined with microbubbles (MBs) has emerged as a potential approach for opening the blood-brain barrier (BBB) for delivering drugs into the brain. However, MBs range in size of microns and thus can hardly extravasate into the brain parenchyma. Recently, growing attention has been paid to gas vesicles (GVs), which are genetically encoded gas-filled nanostructures with protein shells, due to their potential for extravascular targeting in ultrasound imaging and therapy. However, the use of GVs as agents for BBB opening has not yet been investigated.In this study, GVs were extracted and purified from Halobacterium NRC-1. Ultrasound imaging performance of GVs was assessed in vitro and in vivo. Then, FUS/GVs-mediated BBB opening for small molecular Evans blue or large molecular liposome delivery across the BBB was examined.The results showed a good contrast performance of GVs for brain perfusion ultrasound imaging in vivo. At the acoustic negative pressure of 1.5 MPa, FUS/GVs opened the BBB safely, and effectively enhanced Evans blue and 200-nm liposome delivery into the brain parenchyma.Our study suggests that biosynthetic GVs hold great potential to serve as local BBB-opening agents in the development of new targeted drug delivery strategies for central nervous system disorders.
SIRT1 is known to be closely associated with cellular senescence, while the relationship between miR-487a-3p and SIRT1 and their role in mesenchymal stem cells (MSCs) remains unclear. MiRDB analysis showed SIRT1 is a target of miR-487a-3p. Here we investigated whether miR-487a-3p modulates senescence of mesenchymal stem cells by targeting SIRT1. The human MSCs (hMSCs) were divided into control group (NC group), miR-487a-3p Mimics group, pCMV-SIRT+miR-487a-3p Mimics group followed by analysis of miR-487a-3p expression by qPCR and protein level of SIRT1, P21 and P53 by western blot. Dual luciferin report assay verified the binding of miR-487a-3p to SIRT1 mRNA and β -galactosidase activity staining detected hMSCs senescence. miR-487a-3p level was significantly elevated after miR-487a-3p Mimics treatment ( P <0.01) without difference between miR-487a-3p Mimics group and pCMV-SIRT1 group+miR-487a-3pMimics ( P >0.05). miR-487a-3p mimics significantly decreased SIRT1 level ( P < 0.01), which was reversed by pCMVSIRT1 plasmid transfection ( P <0.05). Moreover, miR-487a-3p could bind SIRT1 mRNA 3′-UTR region. Further more, miR-487a-3p Mimics induced cellular senescence as displayed by increased β -galactosidase activity ( P <0.01) and increased level of senescence-related proteins P21 and P53 ( P < 0.01), which were all reversed by overexpression of SIRT1 ( P < 0.05). In conclusion, miR-487a-3p reduced SIRT1 expression, thus promoting hMSCs senescence, while overexpression of SIRT1 could counteract the senescence of hMSCs induced by miR-487a-3p.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
