Gastrointestinal bleeding risk factors in type A aortic dissection post-aortic arch replacement.

Background: Gastrointestinal bleeding (GIB) is a notable complication in patients diagnosed with aortic dissection (AD). We evaluated the outcomes and identified the risk factors associated with GIB in patients with AD. Methods: A retrospective case-control study was conducted on patients diagnosed with type A aortic dissection (TAAD) who underwent total aortic arch replacement (TAAR) at our institution from July 2021 to July 2023. Comprehensive clinical data, laboratory findings, and imaging results were meticulously gathered and analyzed to identify potential risk factors linked to GIB in this patient cohort. Results: Of the 198 AD patients who underwent TAAR, 38 (19.2%) developed postoperative GIB (GIB group), with a median interval of 7 days between surgery and bleeding onset. The GIB group exhibited significantly higher mortality (26.3% vs. 3.1%, P<0.001), prolonged intensive care unit (ICU) stay {15 [interquartile range (IQR), 8-25] vs. 7 (IQR, 5-12) days, P<0.001}, and extended duration of ventilation [168 (IQR, 120-372) vs. 71 (IQR, 34-148) hours, P<0.001] compared to the control group (n=160, 80.8%). Logistic regression analysis identified age >54 years [odds ratio (OR): 3.529], intraoperative red blood cell (RBC) transfusion >600 mL (OR: 3.865), and concomitant celiac trunk and superior mesenteric artery (SMA) hypoperfusion (OR: 15.974) as independent risk factors for GIB in AD patients. Conclusions: GIB subsequent to TAAR in AD patients is linked to adverse prognosis. Factors such as advanced age, extensive intraoperative transfusion, and gastrointestinal (GI) perfusion abnormalities may heighten the risk of GIB in this patient population.

Human aortic smooth muscle cell regulation by METTL3 via upregulation of m6A NOTCH1 modification and inhibition of NOTCH1.

Background: Thoracic aortic dissection (TAD) is a very serious vascular condition that requires immediate treatment. Phenotypic conversion of human aortic smooth muscle cells (HASMCs) has been reported to be a causal factor for TAD development. Genetic variations affecting RNA modification may play a functional role in TAD. In this study, we aimed to explore the potential role of the methyltransferase like 3 (METTL3) and notch homolog 1 (NOTCH1) N6-methyladenosine (m6A) modification mechanisms in HASMCs. Methods: HASMCs were cultured. METTL3 was knocked down and overexpressed. Then, both METTL3 and NOTCH1 were simultaneously knocked down in HASMCs. HASMC proliferation was determined using Cell Counting Kit-8 (CCK-8). METTL3, NOTCH1, α-smooth muscle actin (α-SMA), smooth muscle protein 22-alpha (SM22α), and calponin expressions were monitored with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. An m6A dot blot assay was used to examine the m6A modification levels. The NOTCH1 3' untranslated region (3'UTR) m6A modification was analyzed using SRAMP and RMBase v. 2.0. A methylated RNA immunoprecipitation (MeRIP) assay was used to evaluate the METTL3 overexpression effect on m6A modification of NOTCH1 messenger RNA (mRNA). A dual-luciferase assay was used to investigate the effect of METTL3 binding of the NOTCH1 mRNA m6A modification site. YTH domain family 2 (YTHDF2)-RNA immunoprecipitation (RIP) was used to detect the change in YTHDF2's ability to bind to NOTCH1 mRNA after METTL3 overexpression. Results: Overexpression of METTL3 inhibited α-SMA, SM22α, calponin, and NOTCH1 expressions and promoted HASMC proliferation. Knocking down METTL3 had the opposite effect. The cointerference of the METTL3 and NOTCH1 results suggested that METTL3 regulated NOTCH1, contributing to HASMC phenotypic changes. The MeRIP assay showed that the m6A modification of NOTCH1 mRNA increased after METTL3 overexpression. The dual-luciferase assay indicated that the NOTCH1 mRNA m6A modification site and METTL3 overexpression promoted NOTCH1 mRNA degradation. YTHDF2-RIP further demonstrated that the binding ability of YTHDF2 and NOTCH1 mRNA was enhanced after METTL3 overexpression. Conclusions: METTL3 regulated the phenotypic changes of HASMC by upregulating m6A modification of NOTCH1 and inhibiting NOTCH1.

Defining a postoperative mean arterial pressure threshold in association with acute kidney injury after cardiac surgery: a prospective observational study.

Acute kidney injury (AKI) is a common but fatal complication after cardiac surgery. In the absence of effective treatments, the identification and modification of risk factors has been a major component of disease management. However, the optimal blood pressure target for preventing cardiac surgery-associated acute kidney injury (CSA-AKI) remains unclear. We sought to determine the effect of postoperative mean arterial pressure (MAP) in CSA-AKI. It is hypothesized that longer periods of hypotension after cardiac surgery are associated with an increased risk of AKI. This prospective cohort study was conducted on adult patients who underwent cardiac surgery requiring cardiopulmonary bypass at a tertiary center between October 2018 and May 2020. The primary outcome is the occurrence of CSA-AKI. MAP and its duration in the ranges of less than 65, 65 to 74, and 75 to 84 mmHg within 24 h after surgery were recorded. The association between postoperative MAP and CSA-AKI was examined by using logistic regression. Among the 353 patients enrolled, 217 (61.5%) had a confirmed diagnosis of CSA-AKI. Each 1 h epoch of postoperative MAP less than 65 mmHg was associated with an adjusted odds ratio of 1.208 (95% CI, 1.007 to 1.449; P = 0.042), and each 1 h epoch of postoperative MAP between 65 and 74 mmHg was associated with an adjusted odds ratio of 1.144 (95% CI, 1.026 to 1.275; P = 0.016) for CSA-AKI. A potentially modifiable risk factor, postoperative MAP less than 75 mmHg for 1 h or more is associated with an increased risk of CSA-AKI.

Prediction of acute kidney injury after total aortic arch replacement with serum cystatin C and urine N-acetyl-ß-d-glucosaminidase: A prospective observational study.

BACKGROUND: Acute kidney injury (AKI) after total aortic arch replacement (TAAR) is frequent and associated with adverse outcomes, whereas its early detection remains a challenge. Serum cystatin C (sCysC) and urinary N-acetyl-ß-d-glucosaminidase (uNAG) are clinically available renal biomarkers, but their combination for AKI detection requires more evidence. This study aimed to assess the discriminative abilities of these biomarkers in AKI after TAAR. MATERIALS AND METHODS: Patients undergoing TAAR were included in this prospective observational study. The AKI prediction model was developed and internal verificated, and the significance of each variable was analyzed by random forest (RF). Finally, the best predictive critical values of sCysC and uNAG were explored by the AUC-ROC curve. RESULTS: The AUC-ROC of the prediction model was substantially enhanced by adding sCysC and uNAG (0.909 vs 0.844, p < 0.001), and the clinical utility and risk reclassification were significantly improved. Additionally, the RF showed that sCysC and uNAG ranked first and second. The AUC-ROC for each were 0.864 and 0.802 respectively, and the cut-off values were 1.395 mg/L and 31.90 U/g Cre respectively. CONCLUSION: The prediction model incorporating functional marker sCysC and tubular injury marker uNAG can improve the discriminative abilities of AKI after TAAR.

Indole-3-Propionic Acid as a Potential Therapeutic Agent for Sepsis-Induced Gut Microbiota Disturbance.

The effects of using gut microbiota metabolites instead of live microorganisms to modulate sepsis-induced gut dysbiosis remain largely unknown. We assessed the effects of microbiota metabolite indole-3-propionic acid (IPA) on gut microbiota in mice during sepsis. Sepsis models were constructed by cecal ligation and puncture (CLP) methods. Fecal microbiota composition analysis was performed to characterize the gut microbiota composition. Fecal microbiota transplantation was performed to validate the roles of gut microbiota on sepsis progression. IPA-treated mice exhibited lower serum inflammatory mediator levels and a higher survival rate than those of saline-treated mice after modeling of sepsis, which were negated in the presence of antibiotics. Compared with saline-treated mice after modeling, IPA-treated mice showed a markedly different intestinal microbiota composition, with an enrichment of Bifidobacteriaceae family and a depletion of Enterobacteriaceae family. Mice gavaged with postoperative feces from IPA-treated animals displayed better survival than mice gavaged with feces from saline-treated animals. Overall, these data suggest that IPA offers a microbe-modulated survival advantage in septic mice, indicating that some microbiota metabolites could replace live microorganisms as potential options for regulation of sepsis-induced gut dysbiosis. IMPORTANCE The role of gut microbiota in the pathophysiology of sepsis is gaining increasing attention and developing effective and safe sepsis therapies targeting intestinal microorganisms is promising. Given the safety of probiotic supplementation or fecal microbiota transplantation in critically ill patients, identifying an abiotic agent to regulate the intestinal microbiota of septic patients is of clinical significance. This study revealed that IPA, a microbiota-generated tryptophan metabolite, ameliorated sepsis-induced mortality and decreased the serum levels of proinflammatory cytokines by modulating intestinal microbiota. Although IPA did not increase the abundance and diversity of the microbiota of septic mice, it significantly decreased the number of Enterobacteriaceae family. These findings indicate that a specific microbiota metabolite (e.g., IPA) can mediate the intestinal microbiota apart from FMT or probiotics.

Downregulated ALKBH5 contributes to myocardial ischemia/reperfusion injury by increasing m6A modification of Trio mRNA.

Background: The modification of N6-methyladenosine (m6A) is a dynamic and reversible course that might play a role in cardiovascular disease. However, the mechanisms of m6A modification in myocardial ischemia/reperfusion injury (MIRI) remain unclear. Methods: A mouse model of MIRI and a cell model of oxygen-glucose deprivation/reperfusion (OGD/R) HL-1 cells were employed. In an in vivo study, the total RNA m6A modification levels were determined by dot blot, and the key genes related to m6A modification were screened by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In an in vitro study, the effects of AlkB homolog 5 (ALKBH5), an RNA demethylase, on cell proliferation, cell injury, and apoptosis were detected by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, lactate dehydrogenase (LDH) and cardiac troponin-I (cTnI) levels, and flow cytometry. Besides, the m6A modification-changed and differentially expressed messenger RNA (mRNA) were determined by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) in ALKBH5-overexpressed HL-1 cells. Finally, the mRNA levels of the promising targeted gene were examined by RT-qPCR and its m6A modification levels were examined by MeRIP-qPCR. Results: Our results showed that RNA m6A modification was involved in MIRI, in which ALKBH5 was downregulated. Functionally, by overexpressing or silencing ALKBH5 in experimental cells, we verified its protective properties on cell proliferation, cell injury, and apoptosis in the process of MIRI. Besides, we provided a mass of latent different mRNAs with m6A modification variation in ALKBH5-overexpressed HL-1 cells. Mechanistically, we further screened the most potential targeted mRNAs and suggested that triple functional domain (Trio) mRNA could be upregulated by ALKBH5 by reducing m6A level of Trio. Conclusions: This study demonstrated that the downregulated ALKBH5 might contribute to MIRI process by increasing the m6A modification of Trio mRNA and downregulating Trio.

Variations of urinary N-acetyl-ß-D-glucosaminidase levels and its performance in detecting acute kidney injury under different thyroid hormones levels: a prospectively recruited, observational study.

OBJECTIVE: Changes in thyroid function will be accompanied by changes in urinary N-acetyl-ß-D-glucosaminidase (uNAG) levels. Therefore, whether thyroid hormones interfere the ability of uNAG in detecting acute kidney injury (AKI) has raised concern in patients with critical illness. DESIGN: A prospectively recruited, observational study was performed. SETTING: Adults admitted to the intensive care unit of a grade A tertiary hospital in China. PARTICIPANTS: A total of 1919 critically ill patients were enrolled in the study. MAIN OUTCOME MEASURES: To investigate the variations of the ability of uNAG to detect AKI in patients with critical illness under different thyroid hormones levels (differences in area under the curve (AUC) for uNAG diagnosis and prediction of AKI with different thyroid hormones levels). RESULTS: The bivariate correlation analysis revealed that FT3 and TT3 levels were independently associated with uNAG levels (p<0.001). FT3 and uNAG also showed correlation in multivariable linear regression analysis (p<0.001). After stratification according to the levels of FT3 or TT3, significant variation was observed in the uNAG levels with different quartiles (p<0.05). However, in patients with varying FT3 and TT3 levels, no significant difference was found in the AUCs of uNAG to detect AKI (p>0.05). CONCLUSIONS: Even if uNAG levels varied with FT3 and TT3 levels, these hormones did not interfere with uNAG's ability to detect AKI in patients with critical illness.

MSCs-Derived Extracellular Vesicles Carrying miR-212-5p Alleviate Myocardial Infarction-Induced Cardiac Fibrosis via NLRC5/VEGF/TGF-ß1/SMAD Axis.

The purpose of the present study was to define the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in the progression of myocardial infarction (MI)-induced cardiac fibrosis. An in vitro cell model of hypoxia-induced cardiac fibrosis was constructed in cardiac fibroblasts (CFs). miR-212-5p was poorly expressed in clinical pathological samples and animal models of cardiac fibrosis caused by MI, while miR-212-5p expression was enriched in EVs released from MSCs. EVs from MSCs were isolated, evaluated, and co-cultured with CFs. Dual-luciferase reporter gene assay revealed that miR-212-5p negatively targeted NLRC5 progression of cardiac fibrosis. Following loss- and gain-function assay, EVs expressing miR-212-5p protected against cardiac fibrosis evidenced by reduced levels of α-SMA, Collagen I, TGF-ß1, and IL-1ß. In vivo experiments further confirmed the above research results. Collectively, EVs from MSCs expressing miR-212-5p may attenuate MI by suppressing the NLRC5/VEGF/TGF-ß1/SMAD axis.

Identification and Potential Mechanisms of a 7-MicroRNA Signature That Predicts Prognosis in Patients with Lower-Grade Glioma.

Background: Lower-grade glioma is an intracranial cancer that may develop into glioblastoma with high mortality. The main objective of our study is to develop microRNA for LGG patients which will provide novel prognostic biomarkers along with therapeutic targets. Methods: Clinicopathological data of LGG patients and their RNA expression profile were downloaded through The Cancer Genome Atlas Relevant expression profiles of RNA, and clinicopathological data of the LGG patients had been extracted from the database of "The Cancer Genome Atlas." Differential expression analysis had been conducted for identification of the differentially expressed microRNAs as well as mRNAs in LGG samples and normal ones. ROC curves and K-M plots were plotted to confirm performance and for predictive accuracy. For the confirmation of microRNAs as an independent prognostic factor, an independent prognosis analysis was conducted. Moreover, target differentially expressed genes of these identified prognostic microRNAs that were extracted and protein-protein interaction networks were developed. Moreover, the biological functions of signature were determined through Genome Ontology analysis, genome pathway analysis, and Kyoto Encyclopedia of Genes. Results: 7-microRNA signature was identified that has the ability of categorization of individuals with LGG into high- and low-risk groups on the basis of significant difference in survival during training and testing cohorts (P < 0.001). The 7-microRNA signature had appeared to be robust in predictive accuracy (all AUC> 0.65). It was also approved with multivariate Cox regression along with some traditional clinical practices that we can use 7-microRNA signature for therapeutic purposes as a self-regulating predictive OS factor (P < 0.001). KEGG and Gene Ontology (GO) analyses reported that 7-microRNAs had mainly developed in important pathways related with glioma, e.g., the "cAMP signaling pathway," "glutamatergic synapses," and "calcium signaling pathway". Conclusion: A newly discovered 7-microRNA signature could be a potential target for the diagnosis and treatment for LGG patients.

Analysis of the contribution of 129 candidate genes to thoracic aortic aneurysm or dissection of a mixed cohort of sporadic and familial cases in South China.

Thoracic aortic aneurysm or dissection (TAAD) is a group of life-threatening complex diseases after symptomatic onset with genetic heterogeneity accounting for approximately 20% of cases. Previously, we identified 40 rare variants in 11 TAAD-related core genes among 70 TAAD patients by next-generation sequencing. In this study, we further analyzed the variants in the disease-causing genes in 129 cases of sporadic TAAD and 22 familial cases by whole-exome sequencing. A total of 116 variants in 47 TAAD-related genes were identified, 64.7% (75/116) of which occurred in sporadic TAAD without syndromes, and among these genes, FBN1 was the most common TAAD-related gene. Of the 26.7% (31/116) that were pathogenic or likely pathogenic, almost one third were from sporadic cases without syndromes involving FBN1, SMAD3, SMAD6, MYH11, TGFBR1, MYLK, LOX and LTBP3. Interestingly, the novel VUS (variant of uncertain significance) *879Glu in MCTP2 occurred in two unrelated probands with sporadic acute aortic dissection without a bicuspid aortic valve. Furthermore, more than one variant was detected in 24 patients, and 70.8% (17/24) occurred in sporadic cases. Younger individuals were more likely to carry P/LP (pathogenic or likely pathogenic) variants and harbor more variants. P/LP carriers seem to have a larger aortic diameter, lower D-dimer levels, and a shorter ICU length of stay but longer hospitalization time. In conclusion, we expanded the candidate gene profile of TAAD, especially for sporadic cases without syndromic features. VUSs need further clarification.

Therapeutic management of acute type A aortic intramural hematoma.

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.

Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction.

The ceRNA network involving circular RNAs (circRNAs) is essential in the cardiovascular system. We investigated the underlying ceRNA network involving circHIPK3 in myocardial infarction (MI). After an MI model was established, cardiac function was verified, and myocardial tissue damage in mice with MI was evaluated. A hypoxia model of cardiomyocytes was used to simulate MI in vivo, and the expression of and targeting relationships among circHIPK3, miR-93-5p, and Rac1 were verified. The apoptosis of cardiomyocyte was identified. Gain- and loss-of-functions were performed to verify the ceRNA mechanism. The MI-modeled mice showed cardiac dysfunction and enlarged infarct size. CircHIPK3 was highly expressed in mouse and cell models of MI. Silencing circHIPK3 reduced infarct size, myocardial collagen deposition, and myocardial apoptosis rate and improved cardiac function. CircHIPK3 sponged miR-93-5p, and miR-93-5p targeted Rac1. Overexpression of miR-93-5p inhibited MI-induced cardiomyocyte injury and eliminated the harmful effect of circHIPK3. CircHIPK3 acted as ceRNA to absorb miR-93-5p, thus promoting the activation of the Rac1/PI3K/AKT pathway. We highlighted that silencing circHIPK3 can upregulate miR-93-5p and then inhibit the activation of Rac1/PI3K/Akt pathway, which can improve MI-induced cardiac dysfunction.

Modified Nasoseptal Rescue Flap Technique for Pituitary Adenoma Resection via Endoscopic Endonasal Approach.

ABSTRACT: Nasoseptal rescue flap (NSRF), which preserves the pedicle of the flap and is harvested as a nasoseptal flap (NSF) when intraoperative leakage of cerebrospinal fluid (CSF) occurs, is an alternative strategy for skull base reconstruction in patients with pituitary adenoma resection via an endoscopic endonasal approach. However, in practice, the original NSRF technique cannot meet the needs during operation. Therefore, the authors aimed to describe a modified NSRF technique for the resection of pituitary adenoma via endoscopic endonasal approach and to examine its utility and outcomes. The authors retrospectively analyzed the medical records of 87 consecutive patients with pituitary adenoma who underwent endoscopic endonasal surgery performed using NSRF technique from September 2019 to August 2020. Data on intraoperative CSF leakage, NSF conversion rate, and reconstruction-related complications were analyzed. The average age of patients was 50.1 years (men, 50.5%). Twenty-five cases of intraoperative CSF leakage were observed: 23 cases of low-flow CSF leakage and two cases of high-flow CSF leakage. NSRF was converted to NSF in 11 cases. Two patients experienced postoperative CSF leakage after reconstruction without NSF and required unplanned reoperation to rebuild the skull base with NSF. In conclusion, this modified NSRF utilized a minimally invasive way to provide sufficient surgical corridor without the need for pedicle retraction, and it can be effectively converted to an NSF for skull base reconstruction in patients with pituitary adenoma.

Adjuvant chemotherapy and survival outcome in node-negative breast cancer with a 21-gene recurrence score of 26-30.

Aim: To investigate the benefit of chemotherapy among early-stage breast cancer patients with 21-gene recurrence scores of 26-30. Methods: We identified 3754 patients in the Surveillance, Epidemiology, and End Results database. Results: 57.6% of the patients received adjuvant chemotherapy. Patients with higher tumor grade, larger tumors and younger age were more likely to receive chemotherapy. The receipt of chemotherapy was independently associated with better breast cancer-specific survival than in patients without chemotherapy before (p = 0.016) and after (p = 0.043) propensity score matching. The sensitivity analyses showed that survival gain was pronounced in patients with poorly differentiated or undifferentiated disease. Conclusions: Adjuvant chemotherapy improves the outcome for early-stage breast cancer with 21-gene recurrence score of 26-30, especially for patients with high-grade tumors.

Lay abstract In current clinical practice, the 21-gene recurrence score has been developed for chemotherapy decision-making based on prognostic risk stratification, especially for patients with tumor size ≤5 cm, node-negative, hormone receptor-positive and HER2-negative breast cancer. However, the chemotherapy benefit in breast cancer patients with a 21-gene recurrence score (RS) of 26­30 is unclear. This study aimed to investigate the survival benefit of additional chemotherapy for early-stage breast cancer patients with RS 26­30 using the Surveillance, Epidemiology, and End Results data. Our study suggests that the RS 26­30 group is regarded as a uniform entity by clinicians. Adjuvant chemotherapy improves the outcome for early-stage breast cancer patients with RS 26­30, especially for patients with high-grade tumors.

C-reactive protein concentration as a risk predictor of mortality in intensive care unit: a multicenter, prospective, observational study.

BACKGROUND: It is not clear whether there are valuable inflammatory markers for prognosis judgment in the intensive care unit (ICU). We therefore conducted a multicenter, prospective, observational study to evaluate the prognostic role of inflammatory markers. METHODS: The clinical and laboratory data of patients at admission, including C-reactive protein (CRP), were collected in four general ICUs from September 1, 2018, to August 1, 2019. Multivariate logistic regression was used to identify factors independently associated with nonsurvival. The area under the receiver operating characteristic curve (AUC-ROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the effect size of different factors in predicting mortality during ICU stay. 3 -knots were used to assess whether alternative cut points for these biomarkers were more appropriate. RESULTS: A total of 813 patients were recruited, among whom 121 patients (14.88%) died during the ICU stay. The AUC-ROC values of PCT and CRP for discriminating ICU mortality were 0.696 (95% confidence interval [CI], 0.650-0.743) and 0.684 (95% CI, 0.633-0.735), respectively. In the multivariable analysis, only APACHE II score (odds ratio, 1.166; 95% CI, 1.129-1.203; P = 0.000) and CRP concentration > 62.8 mg/L (odds ratio, 2.145; 95% CI, 1.343-3.427; P = 0.001), were significantly associated with an increased risk of ICU mortality. Moreover, the combination of APACHE II score and CRP > 62.8 mg/L significantly improved risk reclassification over the APACHE II score alone, with NRI (0.556) and IDI (0.013). Restricted cubic spline analysis confirmed that CRP concentration > 62.8 mg/L was the optimal cut-off value for differentiating between surviving and nonsurviving patients. CONCLUSION: CRP markedly improved risk reclassification for prognosis prediction.

The effect of glucocorticoids on serum cystatin C in identifying acute kidney injury: a propensity-matched cohort study.

BACKGROUND: Glucocorticoids may impact the accuracy of serum cystatin C (sCysC) in reflecting renal function. We aimed to assess the effect of glucocorticoids on the performance of sCysC in detecting acute kidney injury (AKI) in critically ill patients. METHODS: A prospective observational cohort study was performed in a general intensive care unit (ICU). Using propensity score matching, we successfully matched 240 glucocorticoid users with 960 non-users among 2716 patients. Serum creatinine (SCr) and sCysC were measured for all patients at ICU admission. Patients were divided into four groups based on cumulative doses of glucocorticoids within 5 days before ICU admission (Group I: non-users; Group II: 0 mg < prednisone ≤50 mg; Group III: 50 mg < prednisone ≤150 mg; Group IV: prednisone > 150 mg). We compared the performance of sCysC for diagnosing and predicting AKI in different groups using the area under the receiver operator characteristic curve (AUC). RESULTS: A total of 240 patients received glucocorticoid medication within 5 days before ICU admission. Before and after matching, the differences of sCysC levels between glucocorticoid users and non-users were both significant (P <  0.001). The multiple linear regression analysis revealed that glucocorticoids were independently associated with sCysC (P <  0.001). After matching, the group I had significantly lower sCysC levels than the group III and group IV (P <  0.05), but there were no significant differences in sCysC levels within different glucocorticoids recipient groups (P > 0.05). Simultaneously, we did not find significant differences in the AUC between any two groups in the matched cohort (P > 0.05). CONCLUSIONS: Glucocorticoids did not impact the performance of sCysC in identifying AKI in critically ill patients.

Author Correction: Identification of Novel Clinically Relevant Variants in 70 Southern Chinese patients with Thoracic Aortic Aneurysm and Dissection by Next-generation Sequencing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Circular RNA involved in the protective effect of losartan on ischemia and reperfusion induced acute kidney injury in rat model.

Although losartan has inhibitory effects on acute kidney injury (AKI), the underlying molecular mechanisms have remained largely unclear. The expressional alteration of circular RNAs (circRNAs) was investigated in the present study to understand the therapeutic effects of losartan against AKI. AKI rat models were established by ischemia and reperfusion (I/R) treatment. Urea and creatinine levels were determined and histological features of kidney tissues examined following hematoxylin and eosin staining. Cell apoptosis was assessed by TUNEL. CircRNA profiles were obtained by RNA-Seq followed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Expression of circRNAs was validated by quantitative RT-PCR. I/R treatment induced an increase in plasma urea and creatinine levels, abnormal kidney tubular structure, and cell apoptosis in Sprague-Dawley (SD) rats, which were effectively inhibited by pre-treatment with losartan. Further RNA-Seq analysis revealed a wide range of differentially expressed circRNAs in I/R rat kidneys, which were reversed by losartan pre-treatment. GO and KEGG analyses revealed that the circRNAs are associated with various biological processes, including the PI3K-Akt signaling pathway. Specifically, circ-Dnmt3a, circ-Akt3, circ-Plekha7, and circ-Me1 were down-regulated in AKI rats and restored by losartan. The current study provides an overview of circRNAs expression profiles based on the inhibitory effects of losartan in ischemic AKI rats.

Rat mRNA expression profiles associated with inhibition of ischemic acute kidney injury by losartan.

Objective: Losartan was reported to inhibit the progression of acute kidney injury (AKI), but little is known about the underlying pharmacological mechanisms. In the present study, the mRNA expression profiles in ischemic AKI rat kidney altered by losartan treatment were analyzed by next-generation deep sequencing technology.Methods: Ischemia and reperfusion treatment was applied to induce AKI in Sprague-Dawley (SD) rats. The urea and creatinine contents in rat blood were measured. H&E staining was performed to evaluate the histological alteration of rat kidney tissues under a microscope. The TUNEL method was applied to analyze apoptosis in rat kidney tissues. The mRNA profiles in rat kidney were analyzed using next-generation deep sequencing. Differential gene expression was confirmed by quantitative qRT-PCR.Results: The rat model of AKI induced by ischemia and reperfusion showed significant increases in urea and creatinine levels, accompanied by a disrupted kidney tubular structure and renal cell apoptosis. Losartan treatment effectively inhibited the changes in urea and creatinine, tubular structure, and apoptosis in AKI rat kidney. A large number of mRNAs were found to be differentially expressed in the kidneys of AKI rats treated with losartan, which are involved in multiple processes and signaling pathways. The expression of nine differentially expressed genes such as monocyte chemoattractant protein-1 (CCL2) and suppressor of cytokine signaling 3 (SOCS3) was confirmed by qRT-PCR and Western blot.Conclusion: Losartan caused significant alterations in the gene expression profile in AKI rat kidney, which mediated its anti-AKI effects.