No abstract

Osmotic response element binding protein (OREBP) is a Rel-like transcription factor critical for cellular osmoresponses. Previous studies suggest that hypertonicity-induced accumulation of OREBP protein might be mediated by transcription activation as well as posttranscriptional mRNA stabilization or increased translation. However, the underlying mechanisms remain incompletely elucidated. Here, we report that microRNAs (miRNAs) play critical regulatory roles in hypertonicity-induced induction of OREBP. In renal medullary epithelial mIMCD3 cells, hypertonicity greatly stimulates the activity of the 3′-untranslated region of OREBP (OREBP-3′UTR). Furthermore, overexpression of OREBP-3′UTR or depletion of miRNAs by knocking-down Dicer greatly increases OREBP protein expression. On the other hand, significant alterations in miRNA expression occur rapidly in response to high NaCl exposure, with miR-200b and miR-717 being most significantly down-regulated. Moreover, increased miR-200b or miR-717 causes significant down-regulation of mRNA, protein and transcription activity of OREBP, whereas inhibition of miRNAs or disruption of the miRNA–3′UTR interactions abrogates the silencing effects. In vivo in mouse renal medulla, miR-200b and miR-717 are found to function to tune OREBP in response to renal tonicity alterations. Together, our results support the notion that miRNAs contribute to the maximal induction of OREBP to participate in cellular responses to osmotic stress in mammalian renal cells.

Background Acute aortic dissection type A is a life-threatening disease required emergency surgery during acute phase. Different clinical manifestations, laboratory tests, and imaging features of patients with acute aortic dissection type A are the risk factors of preoperative mortality. This study aims to establish a simple and effective preoperative mortality risk assessment model for patients with acute aortic dissection type A. Methods A total of 673 Chinese patients with acute aortic dissection type A who were admitted to our hospital were retrospectively included. All patients were unable to receive surgically treatment within 3 days from the onset of disease. The patients included were divided into the survivor and deceased groups, and the endpoint event was preoperative death. Multivariable analysis was used to investigate predictors of preoperative mortality and to develop a prediction model. Results Among the 673 patients, 527 patients survived (78.31%) and 146 patients died (21.69%). The developmental dataset had 505 patients, calibration by Hosmer Lemeshow was significant (χ2 = 3.260, df = 8, P = 0.917) and discrimination by area under ROC curve was 0.8448 (95% CI 0.8007–0.8888). The validation dataset had 168 patients, calibration was significant (χ2 = 5.500, df = 8, P = 0.703) and the area under the ROC curve was 0.8086 (95% CI 0.7291–0.8881). The following independent variables increased preoperative mortality: age (OR = 1.008, P = 0.510), abrupt chest pain (OR = 3.534, P < 0.001), lactic in arterial blood gas ≥ 3 mmol/L (OR = 3.636, P < 0.001), inotropic support (OR = 8.615, P < 0.001), electrocardiographic myocardial ischemia (OR = 3.300, P = 0.001), innominate artery involvement (OR = 1.625, P = 0.104), right common carotid artery involvement (OR = 3.487, P = 0.001), superior mesenteric artery involvement (OR = 2.651, P = 0.001), false lumen / true lumen of ascending aorta ≥ 0.75 (OR = 2.221, P = 0.007). Our data suggest that a simple and effective preoperative death risk assessment model has been established. Conclusions Using a simple and effective risk assessment model can help clinicians quickly identify high-risk patients and make appropriate medical decisions.

Objective: This study aimed to establish a risk assessment model to predict postoperative severe acute lung injury (ALI) risk in patients with acute type A aortic dissection (ATAAD). Methods: Consecutive patients with ATAAD admitted to our hospital were included in this retrospective assessment and placed in the postoperative severe ALI and nonsevere ALI groups based on the presence or absence of ALI within 72 h postoperatively (oxygen index [OI] ≤ 100 mmHg). Patients were then randomly divided into training and validation groups in a ratio of 8:2. Univariate and multivariate stepwise forward logistic regression analyses were used to statistically assess data and establish the prediction model. The prediction model's effectiveness was evaluated via 10-fold cross-validation of the validation group to facilitate the construction of a nomogram. Results: After the screening, 479 patients were included in the study: 132 (27.6%) in the postoperative severe ALI group and 347 (72.4%) in the postoperative nonsevere ALI group. Based on multivariate logistics regression analyses, the following variables were included in the model: coronary heart disease, cardiopulmonary bypass (CPB) ≥ 257.5 min, left atrium diameter ≥ 35.5 mm, hemoglobin ≤ 139.5 g/L, preCPB OI ≤ 100 mmHg, intensive care unit OI ≤ 100 mmHg, left ventricular posterior wall thickness ≥ 10.5 mm, and neutrophilic granulocyte percentage ≥ 0.824. The area under the receiver operating characteristic (ROC) curve of the modeling group was 0.805 and differences between observed and predicted values were not deemed statistically significant via the Hosmer-Lemeshow test (χ 2 = 6.037, df = 8, p = .643).For the validation group, the area under the ROC curve was 0.778, and observed and predicted value differences were insignificant when assessed using the Hosmer-Lemeshow test (χ 2 = 3.3782, df = 7; p = .848). The average 10-fold crossvalidation score was 0.756. Conclusions:This study established a prediction model and developed a nomogram to determine the risk of postoperative severe ALI after ATAAD. Variables used in the model were easy to obtain clinically and the effectiveness of the model was good.

Objective: This study aimed to establish a risk assessment model to predict postoperative severe acute lung injury (ALI) risk in patients with acute type A aortic dissection (ATAAD). Methods: Consecutive patients with ATAAD admitted to our hospital were included in this retrospective assessment and placed in the postoperative severe ALI and non-severe ALI groups based on the presence or absence of ALI within 72 h postoperatively (oxygen index (OI) ≤100 mmHg). Patients were then randomly divided into training and validation groups in a ratio of 8:2. Logistic regression analyses were used to statistically assess data and establish the prediction model. The prediction model’s effectiveness was evaluated via tenfold cross-validation of the validation group to facilitate construction of a nomogram. Results: After screening, 479 patients were included in the study: 132 (27.5%) in the postoperative severe ALI group and 347 (72.5%) in the postoperative non-severe ALI group. Based on logistics regression analyses, the following variables were included in the model: coronary heart disease (CHD), cardiopulmonary bypass (CPB) ≥257.5 min, left atrium (LA) diameter ≥35.5 mm, hemoglobin ≤139.5 g/L, preCPB OI ≤100 mmHg, intensive care unit (ICU) OI ≤100 mmHg, left ventricular posterior wall thickness (LVPWT) ≥10.5 mm, and neutrophilic granulocyte percentage (NEUT) ≥0.824. The area under the receiver operating characteristic (ROC) curve of the modeling group was 0.805, and differences between observed and predicted values were not deemed statistically significant via the Hosmer–Lemeshow test (χ2=6.037, df=8, P=0.643). For the validation group, the area under the ROC curve was 0.778, and observed and predicted value differences were insignificant when assessed using the Hosmer–Lemeshow test (χ =3.3782, df=7; P=0.848). The average tenfold cross-validation score was 0.756. Conclusions: This study established a prediction model and developed a nomogram to determine the risk of postoperative severe ALI after ATAAD. Variables used in the model were easy to obtain clinically and the effectiveness of the model was good.

Objectives The proper therapeutic management for acute type A aortic intramural hematoma (IMH) is still controversial. The purpose of this study was to compare the outcomes following emergency surgery or conservative treatment for patients with this disease. Methods From January 2015 to December 2018, 124 consecutive patients were diagnosed with an acute type A aortic IMH and were included in this study. According to our surgical indications, they were divided into two groups: an operation group (OG) and a conservative treatment group (CG). Results Of 124 patients, 83 (66.9%) patients accepted emergency surgery and 41 (33.1%) patients accepted strict conservative treatment. There were no differences between these two groups in early mortality and complications. However, the late mortality of patients in the CG was significantly higher than for patients in the OG. A maximum aortic diameter in the ascending aorta and aortic arch ≥ 45 mm and maximum thickness of IMH in the same section ≥ 8 mm were risk factors for IMH related death in patients undergoing conservative treatment. Conclusions The mortality associated with emergency surgery for patients with acute type A aortic IMH was satisfactory. In clinical centers with well-established surgical techniques and postoperative management, emergency surgical treatment may provide a better outcome than medical treatment for patients with acute type A aortic IMH.

BackgroundAcute type A aortic dissection (ATAAD) is a rare, life-threatening condition affecting the aorta. This study explores the relationship between the level of admission D-dimer, which was assessed during the first 2 h from admission, and in-hospital major adverse events (MAE) with ATAAD.MethodsA total of 470 patients with enhanced computed tomography (CT) confirmed diagnosis of ATAAD who underwent operation treatment in Guangdong Provincial People's hospital between September 2017 and June 2021 were enrolled in the present study. The X-tile program was used to determine the optimal D-dimer thresholds for risk. Restricted cubic spline (RSC) was performed to assess the association between D-dimer and endpoint. The perioperative data were compared between the two groups, univariate and multivariate analyses were used to investigate the risk factors of major adverse events (in-hospital mortality, gastrointestinal bleeding, paraplegia, acute kidney failure, reopen the chest, low cardiac output syndrome, cerebrovascular accident, respiratory insufficiency, MODS, gastrointestinal bleeding, and severe infection).ResultsAmong 470 patients, 151 (32.1%) had MAE. In-hospital mortality was 7.44%. The patients with D-dimer &gt;14,500 ng/ml were more likely to present with acute kidney failure, low cardiac output, cerebrovascular accident, multiple organ dysfunction syndromes (MODS), gastrointestinal bleeding, and severe infection. D-dimer level was an independent risk factor for acute kidney failure (OR 2.09, 95% CI: 1.25–3.51, p = 0.005), MODS (OR 6.40, 95% CI: 1.23–33.39, p = 0.028), gastrointestinal bleeding (OR 17.76, 95% CI: 1.99–158.78, p = 0.010) and mortality (OR 3.17, 95% CI: 1.32–7.63, p = 0.010). Multivariate regression analysis of adverse events also suggested that D-dimer &gt;14,500 ng/ml (OR 1.68, 95% CI: 1.09–2.61, p = 0.020) was the independent risk factor of major adverse events.ConclusionsIncreasing D-dimer levels were independently associated with the in-hospital MAE and thus can be used as a useful prognostic biomarker before the surgery.

Acute Type A Aortic Dissection (ATAAD) is a kind of cardiovascular disease which seriously threatens human life and health. Surgical treatment is currently recognized as the standard treatment for ATAAD. It has the characteristics of rapid onset, long operation time, and worse post-operative prognosis than other routine cardiac surgeries. Preoperative biomarkers correlated with the outcome of ATAAD was rarely reported. Future research should be directed toward finding out some useful predictive biomarkers and assessing their potential treatment value, in the hope of improving the postoperative prognosis of ATAAD. Von Willebrand factor (vWF) is considered to be closely related to pathophysiological processes such as blood coagulation and vascular inflammation. Its deficiency or elevation may affect patients' blood coagulation condition and postoperative intravascular inflammation, thus affecting the occurrence of postoperative hemorrhagic complications. The purpose of this study is to investigate the effect of vWF on the early postoperative outcome of patients with ATAAD. Method and analysis: Patients with ATAAD who receive surgical treatment in our center from April 1, 2021 to April 1, 2022 will be prospectively included. According to the preoperative vWF measurement, enrolled patients will be divided into two groups: normal vWF (normal level of vWF: NL-vWF, reference value of 50–160%) group and abnormal vWF (Disrupted level of vWF: DL-vWF) group. The preoperative baseline data (including demographic characteristics, comobidities and malperfusion syndrome state, imaging examination, and laboratory examination), and surgical data will be documented. Primary and secondary endpoints events (described in part 2.4) will be assessed and recorded. We will use propensity score approach to account for baseline differences between DL-vWF group and NL-vWF group, and compare the early postoperative outcomes for a purpose of assessing the effect of vWF on the early postoperative outcomes of patients with ATAAD. Highlights