Rationale: Despite recent studies indicating a crucial role of ecto-5′-nucleotidase (CD73) on T cells in cardiac injury after ischemia/reperfusion, the involvement of CD73 + regulatory T cells (Tregs) in cardiac repair post-myocardial infarction (MI) remains unclear. We sought to investigate the contribution of CD73 on Tregs to the resolution of cardiac inflammation and remodeling after MI. Methods: Cardiac function, tissue injury, Tregs percentage in injured hearts, and purinergic signaling changes in cardiac FoxP3 + Tregs were analyzed after permanent descending coronary artery ligation. CD73 knockout Tregs were used to determine the function of CD73 on Tregs. Peripheral blood mononuclear cells (PBMCs) from acute myocardial infarction (AMI) patients and matched non-MI subjects were assessed via flow cytometry. Results: Cardiac Tregs exhibited distinction of purinergic signaling post MI with dramatically high level of CD73 compared to the sham Tregs. CD73 deficiency decreased the tissue tropism, and impaired the immunosuppressive and protective function of Tregs in cardiac healing. Administration of low-dose of IL-2/anti-IL-2 complex resulted in FoxP3 + CD73 + Tregs expansion in the heart and contributed to the recovery of cardiac function. CD73 derived from FoxP3 + Tregs could bind to FoxP3 - effector T-cells and inhibit the production of multiple inflammatory cytokines. In AMI patients, CD73 expressions on both CD4 + cells and FoxP3 + Tregs decreased in PBMCs. Moreover, CD73 expressions on CD4 + T cells were negatively correlated with the levels of NT pro-BNP and myocardial zymogram in serum. Conclusions: Our findings indicated the importance of FoxP3 + CD73 + Tregs in inflammation resolution and cardiac healing post-MI.
Background Laparoscopic colorectal surgery has been proved to have similar oncological outcomes with open surgery. Due to the lack of tactile perception, surgeons may have misjudgments in laparoscopic colorectal surgery. Therefore, the accurate localization of a tumor before surgery is important, especially in the early stages of cancer. Autologous blood was thought a feasible and safe tattooing agent for preoperative endoscopic localization but its benefits remain controversial. We therefore proposed this randomized trial to the accuracy and safety of autogenous blood localization in small, serosa-negative lesion which will be resected by laparoscopic colectomy. Methods The current study is a single-center, open-label, non-inferiority, randomized controlled trial. Eligible participants would be aged 18–80 years and diagnosed with large lateral spreading tumors that could not be treated endoscopically, malignant polyps treated endoscopically that required additional colorectal resection, and serosa-negative malignant colorectal tumors (≤ cT3). A total of 220 patients would be randomly assigned (1:1) to autologous blood group or intraoperative colonoscopy group. The primary outcome is the localization accuracy. The secondary endpoint is adverse events related to endoscopic tattooing. Discussion This trial will investigate whether autologous blood marker achieves similar localization accuracy and safety in laparoscopic colorectal surgery compared to intraoperative colonoscopy. If our research hypothesis is statistically proved, the rational introduction of autologous blood tattooing in preoperative colonoscopy can help improve identification of the location of tumors for laparoscopic colorectal cancer surgery, performing an optimal resection, and minimizing unnecessary resections of normal tissues, thereby improving the patient’s quality of life. Our research data will also provide high quality clinical evidence and data support for the conduction of multicenter phase III clinical trials. Trial registration This study is registered with ClinicalTrials.gov, NCT05597384. Registered 28 October 2022
Background There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFTR) technique for GISTs. Methods In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. Results The median tumor size was 2.5 cm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (> 3.0 cm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were discharged within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant metastasis. Conclusions NT-EFTR was a feasible method for the resection of gastric GISTs and can be expected to achieve complete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural difficulty.
Sound barriers are widely used as an important engineering measure to mitigate traffic noise pollution in urban elevated roads. However, structure design codes on sound barrier used in urban viaduct is empty, which is a key reason for the short service life of sound barrier. Numerical simulation of characteristics of running cars induced wind loads on sound barrier of elevated roads is carried out based on the method of computational fluid dynamics. The changing course of wind loads on the surface of sound barrier is reappeared in the process of cars passing by the sound barrier. The distribution rule of wind loads on the surface of sound barrier at different space positions is revealed. Influence factors of wind loads on surface of sound barrier are discussed by parameter analysis. The conclusions shows that running cars induced wind loads on sound barrier of elevated roads should considered as one main design loads, especially for the anti-fatigue design of steel columns of plate-inserted sound barrier.
BackgroundMany COVID-19 patients have been discharged, but lung injury, including pulmonary fibrosis, might lead to long-term impairment. This study aimed to evaluate predictors and monitors of pulmonary fibrosis in patients with COVID-19.MethodsThirty-five convalescent patients with severe COVID-19, after appropriate medical treatments, were recruited. According to evidence of fibrosis on initial computed tomography (CT), the patients were divided into mild-to-moderate and severe groups. Levels of transforming growth factor beta (TGF-β), chemokine ligand 18 (CCL18), type III procollagen peptide (PⅢP), hyaluronic acid (HA), laminin (LN), and type IV collagen (CⅣ) were determined. Laboratory tests, clinical data, and CT features at different stages were collected and analyzed, and the prognostic performance of these parameters was evaluated.ResultsSevere fibrosis was found in 76.29% (26/35) of patients. However, most baseline laboratory characteristics were normal. Fibrosis indicators (TGF-β: 66.67±158.57 vs 55.84±126.43 pg/mL, P=0.006; CCL18: 364.27±167.70 vs 84.47±60.67 ng/mL, P=0.000; PⅢP: 54.12±55.34 vs 17.15±2.48 ng/mL, P=0.000; HA: 122.47±78.84 vs 59.74±18.01 ng/mL, p=0.000; LN: 55.43±46.44 vs 24.25±7.79 ng/mL, P=0.000; CⅣ: 24.77±14.97 vs 15.32±1.15 ng/mL, P=0.001) were elevated in patients compared with controls. Over 90 days’ follow-up, HRCT scores gradually decreased from 22.48±16.13 to 10.33±11.11 (P<0.001), and mMRC scores decreased from 3.27±0.32 to 1.48±0.33, and all fibrosis indicators, except for PⅢP, gradually declined with the improvement of pulmonary fibrosis. Moreover, TGF-β and CCL18 levels were lower in the mild-to-moderate than severe fibrosis group (88.16±97.45 vs 205.93±170.57 pg/mL, P=0.024; 241.84±125.37 vs 366.64±161.06 ng/mL, P=0.038), and patients with elevated baseline levels of serum TGF-β and CCL18 had longer rehabilitation times.ConclusionsTGF-β and CCL18 may be promising biomarkers for predicting and monitoring the development of pulmonary fibrosis in patients with COVID-19.
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