Bestrophin3 Deficiency in Vascular Smooth Muscle Cells Activates MEKK2/3-MAPK Signaling to Trigger Spontaneous Aortic Dissection.

BACKGROUND: Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive. METHODS: Smooth muscle cell-specific and endothelial cell-specific Best3 knockout mice (Best3SMKO and Best3ECKO, respectively) were engineered to investigate the role of Best3 in vascular pathophysiology. Functional studies, single-cell RNA sequencing, proteomics analysis, and coimmunoprecipitation coupled with mass spectrometry were performed to evaluate the function of Best3 in vessels. RESULTS: Best3 expression in aortas of human AD samples and mouse AD models was decreased. Best3SMKO but not Best3ECKO mice spontaneously developed AD with age, and the incidence reached 48% at 72 weeks of age. Reanalysis of single-cell transcriptome data revealed that reduction of fibromyocytes, a fibroblast-like smooth muscle cell cluster, was a typical feature of human ascending AD and aneurysm. Consistently, Best3 deficiency in smooth muscle cells decreased the number of fibromyocytes. Mechanistically, Best3 interacted with both MEKK2 and MEKK3, and this interaction inhibited phosphorylation of MEKK2 at serine153 and MEKK3 at serine61. Best3 deficiency induced phosphorylation-dependent inhibition of ubiquitination and protein turnover of MEKK2/3, thereby activating the downstream mitogen-activated protein kinase signaling cascade. Furthermore, restoration of Best3 or inhibition of MEKK2/3 prevented AD progression in angiotensin II-infused Best3SMKO and ApoE-/- mice. CONCLUSIONS: These findings unveil a critical role of Best3 in regulating smooth muscle cell phenotypic switch and aortic structural integrity through controlling MEKK2/3 degradation. Best3-MEKK2/3 signaling represents a novel therapeutic target for AD.

Risk factors associated with surgical site infections in patients undergoing cardiothoracic surgery: A systematic review and meta-analysis.

Surgical site infections (SSIs) following cardiothoracic surgery can pose significant challenges to patient recovery and outcome. This systematic review and meta-analysis aim to identify and quantify the risk factors associated with SSIs in patients undergoing cardiothoracic surgery. A comprehensive literature search adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and based on the PICO paradigm was conducted across four databases: PubMed, Embase, Web of Science and the Cochrane Library, without any temporal restrictions. The meta-analysis incorporated studies detailing the risk factors for post-operative sternal infections, especially those reporting odds ratios (OR) or relative risks with 95% confidence intervals (CI). Quality assessment of the studies was done using the Newcastle-Ottawa Scale. Statistical analysis was executed using the chi-square tests for inter-study heterogeneity, with further analyses depending on I2 values. Sensitivity analyses were performed, and potential publication bias was also assessed. An initial dataset of 2442 articles was refined to 21 articles after thorough evaluations based on inclusion and exclusion criteria. Patients with diabetes mellitus have an OR of 1.80 (95% CI: 1.40-2.20) for the incidence of SSIs, while obese patients demonstrate an OR of 1.63 (95% CI: 1.40-1.87). Individuals who undergo intraoperative blood transfusion present an OR of 1.13 (95% CI: 1.07-1.18), and smokers manifest an OR of 1.32 (95% CI: 1.03-1.60). These findings unequivocally indicate a pronounced association between these factors and an elevated risk of SSIs post-operatively. This meta-analysis confirms that diabetes, obesity, intraoperative transfusion and smoking heighten the risk of SSIs post-cardiac surgery. Clinicians should be alert to these factors to optimise patient outcomes.

MitraClip used for severe mitral regurgitation after surgery for type A aortic dissection combined with Marfan syndrome.

Mitral regurgitation is a rare but catastrophic condition in patients after surgery for type A aortic dissection. The second thoracotomy to complete the mitral valve operation could be fatal. Here, we report a case of severe mitral regurgitation treated with MitraClip in a 53-year-old woman after surgery for type A aortic dissection combined with Marfan syndrome. She was discharged uneventfully, and a significant reduction of regurgitation of mitral valve and tricuspid valve was observed at the 6-month follow-up. MitraClip could be an alternative device for such high-risk patients.

Niche Differentiation Among Canonical Nitrifiers and N2O Reducers Is Linked to Varying Effects of Nitrification Inhibitors DCD and DMPP in Two Arable Soils.

The efficacy of nitrification inhibitors (NIs) dicyandiamide (DCD) and 3,4-dimethylpyrazole phosphate (DMPP) varies with soil types. Understanding the microbial mechanisms for this variation may lead to better modelling of NI efficacy and therefore on-farm adoption. This study addressed the response patterns of mineral nitrogen, nitrous oxide (N2O) emission, abundances of N-cycling functional guilds and soil microbiota characteristics, in relation to urea application with or without DCD or DMPP in two arable soils (an alkaline and an acid soil). The inhibition of nitrification rate and N2O emission by NI application occurred by suppressing ammonia-oxidizing bacteria (AOB) abundances and increasing the abundances of nosZI-N2O reducers; however, abundances of ammonia-oxidizing archaea (AOA) were also stimulated with NIs-added in these two arable soils. DMPP generally had stronger inhibition efficiency than DCD, and both NIs' addition decreased Nitrobacter, while increased Nitrospira abundance only in alkaline soil. N2O emissions were positively correlated with AOB and negatively correlated with nosZI in both soils and AOA only in acid soil. Moreover, N2O emissions were also positively correlated with nirK-type denitrifiers in alkaline soil, and clade A comammox in acid soil. Amendment with DCD or DMPP altered soil microbiota community structure, but had minor effect on community composition. These results highlight a crucial role of the niche differentiation among canonical ammonia oxidizers (AOA/AOB), Nitrobacter and Nitrospira, as well as nosZI- and nosZII-N2O reducers in determining the varying efficacies of DCD and DMPP in different arable soils.

A circular network of purine metabolism as coregulators of dilated cardiomyopathy.

BACKGROUND: The crosstalk of purine biosynthesis and metabolism exists to balance the cell energy production, proliferation, survival and cytoplasmic environment stability, but disorganized mechanics of with respect to developing heart failure (HF) is currently unknown. METHODS: We conducted a multi-omics wide analysis, including microarray-based transcriptomes, and full spectrum metabolomics with respect to chronic HF. Based on expression profiling by array, we applied a bioinformatics platform of quantifiable metabolic pathway changes based on gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), Shapley Additive Explanations (SHAP), and Xtreme Gradient Boosting (XGBoost) algorithms to comprehensively analyze the dynamic changes of metabolic pathways and circular network in the HF development. Additionally, left ventricular tissue from patients undergoing myocardial biopsy and transplantation were collected to perform the protein and full spectrum metabolic mass spectrometry. RESULTS: Systematic bioinformatics analysis showed the purine metabolism reprogramming was significantly detected in dilated cardiomyopathy. In addition, this result was also demonstrated in metabolomic mass spectrometry. And the differentially expressed metabolites analysis showing the guanine, urea, and xanthine were significantly detected. Hub markers, includes IMPDH1, ENTPD2, AK7, AK2, and CANT1, also significantly identified based on XGBoost, SHAP model and PPI network. CONCLUSION: The crosstalk in the reactions involved in purine metabolism may involving in DCM metabolism reprogramming, and as coregulators of development of HF, which may identify as potential therapeutic targets. And the markers of IMPDH1, ENTPD2, AK7, AK2, and CANT1, and metabolites involved in purine metabolism shown an important role.

Identification of a Novel 15q21.1 Microdeletion in a Family with Marfan Syndrome.

Background: Marfan syndrome (MFS) is a connective tissue disease involving multiple systems, with thoracic aortic aneurysm (TAA) as the most common life-threatening manifestation. Method: A pedigree with TAA was investigated, and peripheral venous blood was extracted from six family members. After whole exome sequencing (WES) and chromosomal microarray analysis (CMA) in these individuals, bioinformatics and inheritance analyses were performed. Result: WES revealed a novel, small, 0.76 Mb microdeletion in 15q21.1, which cosegregated with the disease phenotype in the family and led to the haploinsufficiency of the fibrillin 1 (FBN1) gene, which is associated with MFS. This small copy number variant (CNV) was confirmed by CMA. Conclusion: Our study expands the phenotypic spectrum of the pathogenic CNV associated with MFS, thereby facilitating clinical genetic diagnosis and future genetic counseling for this family.

Reconstruction of aortic sinus using patches in patients with acute type A aortic dissection.

OBJECTIVES: Acute type A aortic dissection involving the aortic sinus is often combined with varying degrees of aortic regurgitation, while the structure of the aortic valve is often undamaged. The aim of this study was to evaluate the clinical effects of reconstruction of the aortic sinus using patches in patients with acute type A aortic dissection. METHODS: From January 2016 to December 2019, 52 patients with acute type A aortic dissection involving the aortic sinus were treated with aortic sinus reconstruction using pericardial or artificial vascular patches. The clinical and follow-up data were summarized. RESULTS: Bovine pericardial patches were used in 31 cases and artificial vascular patches were used in 21 cases for aortic sinus reconstruction. Cardiopulmonary bypass time was (250.4 ± 65.7) min, aortic cross clamp time was (143.7 ± 42.3) min, and hypothermic circulatory arrest time was (9.6 ± 8.1) min. Three patients died in hospital, with a mortality rate of 5.8%. Fifteen patients (28.8%) had mild postoperative aortic regurgitation. The follow-up duration was 40 ± 12 (range, 21-66) months. Five patients (10.2%) developed moderate to severe aortic regurgitation and 3 (6.1%) died during the follow-up period. CONCLUSIONS: The application of patches for aortic sinus reconstruction is a relatively easy method in aortic valve-sparing root reconstruction for acute type A aortic dissection involving the aortic sinus. The clinical and follow-up results are favorable.

Aortic Repair Through a Left Thoracotomy in a 12-Year-Old Child with Traumatic Aortic Pseudoaneurysm: A Case Report.

Traumatic pseudoaneurysm of the descending aorta is a rare but life-threatening disease, especially in children. Open surgical replacement and thoracic endovascular repair in treating traumatic pseudoaneurysm to prevent aortic rupture rarely have been reported in children. Here, we present a rare case of aortic pseudoaneurysm caused by trauma in a 12-year-old child treated with an alternative surgical strategy. Aortic repair without an implant assisted by distal perfusion was performed through a left thoracotomy. The child satisfactorily recovered, was discharged, and remained in a good condition during the follow-up period.

Calcitonin gene-related peptide receptor antagonist BIBN4096BS regulates synaptic transmission in the vestibular nucleus and improves vestibular function via PKC/ERK/CREB pathway in an experimental chronic migraine rat model.

BACKGROUND: Vestibular symptoms are frequently reported in patients with chronic migraine (CM). However, whether vestibular symptoms arise through overlapping neurobiology of migraine remains to be elucidated. The neuropeptide calcitonin gene-related peptide (CGRP) and CGRP1 receptor play important pathological roles in facilitating central sensitization in CM. Therefore, we aimed to investigate whether CGRP1 receptor contributes to vestibular dysfunction after CM by improving synaptic transmission in the vestibular nucleus (VN). METHODS: A CM rat model was established by recurrent intermittent administration of nitroglycerin (NTG). Migraine- and vestibular-related behaviors were assessed. CGRP1 receptor specific antagonist, BIBN4096BS, and protein kinase C (PKC) inhibitor chelerythrine chloride (CHE) were administered intracerebroventricularly. The expressions of CGRP and CGRP1 receptor components, calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) were evaluated by western blot, immunofluorescent staining and quantitative real-time polymerase chain reaction in the vestibular nucleus (VN). Synaptic associated proteins and synaptic morphological characteristics were explored by western blot, transmission electron microscope, and Golgi-cox staining. The expressions of PKC, phosphorylated extracellular signal regulated kinase (p-ERK), phosphorylated cAMP response element-binding protein at serine 133 site (p-CREB-S133) and c-Fos were detected using western blot or immunofluorescent staining. RESULTS: The expressions of CGRP, CLR and RAMP1 were significantly upregulated in CM rats. CLR and RAMP1 were expressed mainly in neurons. BIBN4096BS treatment and PKC inhibition alleviated mechanical allodynia, thermal hyperalgesia and vestibular dysfunction in CM rats. Additionally, BIBN4096BS treatment and PKC inhibition markedly inhibited the overexpression of synaptic associated proteins and restored the abnormal synaptic structure in VN after CM. Furthermore, BIBN4096BS treatment dysregulated the expression levels of PKC, p-ERK and p-CREB-S133, and attenuated neuronal activation in VN after CM. CONCLUSIONS: The present study demonstrated that CGRP1 receptor inhibition improved vestibular function after CM by reversing the aberrant synaptic transmission via downregulating PKC/ERK/CREB signaling pathway. Therapeutic interventions by inhibiting CGRP/CGRP1 signaling may be a new target for the treatment of vestibular symptoms in CM.

Effect of P availability on straw-induced priming effect was mainly regulated by fungi in croplands.

Phosphorus (P) accumulation in croplands resulting from ever-increasing input of P fertilizer strongly influences soil microbial growth and activities, which is expected to alter the soil priming effect (PE) induced by plant residue. However, the effect of P availability on the magnitude and direction of PE remains largely unexplored and the underlying microbial mechanisms are still unclear. Therefore, a 40-day incubation experiment was established by adding C4-maize straw to C3-soils with or without long-term P fertilizer inputs to investigate PE and accompanied dynamics of microbiota. The results revealed that in both soils, straw application caused positive real PEs via a "microbial co-metabolism" mechanism, accompanied by a microbial succession from the dominance of r- and K-strategists to K-strategists (mainly fungi). In addition, long-term amendment with P increased PE by 83.2% compared with no P fertilization control, which was mainly mediated by K-strategists, especially the fungal families Chaetomiaceae and Myrmecridiaceae. The increased PE was accompanied by enhanced microbial biomass carbon, extracellular enzyme activities, and bacterial gene abundance, confirming the "stoichiometric decomposition" theory. Meanwhile, deviating from the conventional paradigm, higher phosphatase activity and lower enzymatic stoichiometry of carbon (C)-to-P ratios in high-P soil compared with that in low-P soil suggested stronger "P mining" with high-P availability.

Astilbin Protects Against Carbon Tetrachloride-Induced Liver Fibrosis in Rats.

BACKGROUND: Hepatic fibrosis is an inflammatory liver disease, and there is no effective therapy at present. Astilbin is a bioactive ingredient found in many medicinal and food plants, with antioxidative, anti-inflammatory, and antitumor properties. OBJECTIVES: This study aimed to investigate the protective effect and related molecular mechanism of astilbin against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Liver fibrosis was induced by injection of CCl4 in male Sprague-Dawley rats, and those rats were then treated with astilbin at different concentrations. Pathological changes, collagen production, inflammatory cytokine, and oxidative stress were evaluated to evaluate the effects of astilbin on CCl4-induced hepatic fibrosis. Real-time PCR and western blot were performed to detect the mRNA and protein expression of indicated genes. RESULTS: We discovered that CCl4 caused significant fibrosis damage in rat liver, and astilbin dose-dependently improved the liver functions and fibrosis degree. Astilbin treatment significantly decreased collagen production, inflammatory response, and oxidative stress in vivo. Mechanically, administration of astilbin obviously elevated the hepatic levels of Nrf2 and its downstream components, including NAD(P)H:quinone oxidoreductase 1 (Nqo1), heme oxygenase (HO-1), glutamate-cysteine ligase catalytic subunit, and glutamate cysteine ligase modifier. CONCLUSIONS: Taken together, these findings demonstrate that astilbin could protect against CCL4 induced-liver fibrosis in rats.

Outcomes of long versus short stent cronus hybrid prosthesis in type A aortic dissection: A single centre experience.

OBJECTIVES: The frozen elephant trunk (FET) technique has become an important tool in the treatment of acute type A aortic dissection. The aim of this study was to evaluate the effect of long FET on spinal cord injury (SCI) and distal aortic remodeling after acute type A aortic dissection based on clinical and radiological outcomes. METHODS: From January 2018 to November 2019, 158 patients (mean age 51.8 years [range: 32-78 years], 88.6% male) with acute type A aortic dissection were treated by FET with 100 mm (n = 113) or 150 mm (n = 45) open hybrid stent graft prosthesis. Patients were divided into two groups according to the length of FET. The clinical and radiological outcomes of the patients were reviewed retrospectively. RESULTS: Postoperative outcomes did not differ significantly: in-hospital mortality (9.7% vs. 6.7%, p = .758) and SCI (5.3% vs. 2.2%, p = .674). Aortic remodeling, which was evaluated by aortic diameter, true lumen diameter, false lumen (FL) diameter and the rate of FL complete thrombosis, was more positive in long FET group in the descending thoracic aorta during the follow-up period. At the abdominal level, there was no statistically significant difference between the two groups. CONCLUSIONS: The long version of FET does not increase the risk of SCI in patients with acute type A aortic dissection. The application of long FET can achieve better results in terms of remodeling of the thoracic aorta in the short- and medium-term follow-up.

Multi-Level Fusion Temporal-Spatial Co-Attention for Video-Based Person Re-Identification.

A convolutional neural network can easily fall into local minima for insufficient data, and the needed training is unstable. Many current methods are used to solve these problems by adding pedestrian attributes, pedestrian postures, and other auxiliary information, but they require additional collection, which is time-consuming and laborious. Every video sequence frame has a different degree of similarity. In this paper, multi-level fusion temporal-spatial co-attention is adopted to improve person re-identification (reID). For a small dataset, the improved network can better prevent over-fitting and reduce the dataset limit. Specifically, the concept of knowledge evolution is introduced into video-based person re-identification to improve the backbone residual neural network (ResNet). The global branch, local branch, and attention branch are used in parallel for feature extraction. Three high-level features are embedded in the metric learning network to improve the network's generalization ability and the accuracy of video-based person re-identification. Simulation experiments are implemented on small datasets PRID2011 and iLIDS-VID, and the improved network can better prevent over-fitting. Experiments are also implemented on MARS and DukeMTMC-VideoReID, and the proposed method can be used to extract more feature information and improve the network's generalization ability. The results show that our method achieves better performance. The model achieves 90.15% Rank1 and 81.91% mAP on MARS.

Enhancing the Electrochemical Performance of a High-Voltage LiNi0.5 Mn1.5 O4 Cathode in a Carbonate-Based Electrolyte with a Novel and Low-Cost Functional Additive.

Butyric anhydride (BA) is used as an effective functional additive to improve the electrochemical performance of a high-voltage LiNi0.5 Mn1.5 O4 (LNMO) cathode. In the presence of 0.5 wt % BA, the capacity retention of a LNMO/Li cell is significantly improved from 15.3 to 88.4 % after 200 cycles at 1 C. Furthermore, the rate performance of the LNMO/Li cell is also effectively enhanced, and the capacity goes up to 112 mAh g-1 even at 5 C, which is considerably higher than that of a LNMO/Li cell in electrolyte without BA additive (95.4 mAh g-1 at 5 C). Linear sweep voltammetry and cyclic voltammetry results reveal that the BA additive can be preferentially oxidized to construct a stable cathode electrolyte interphase (CEI) film on the LNMO cathode. Subsequently, the BA-derived CEI film can alleviate the decomposition of the electrolyte and the dissolution of Mn and Ni ions from the LNMO cathode as well as maintain the structural stability of LNMO during the cycling process; this leads to outstanding electrochemical performance. Thus, this work provides an effective and low-cost functional electrolyte for high-voltage LNMO-based LIBs.

Involvement of miR-145 in the development of aortic dissection via inducing proliferation, migration, and apoptosis of vascular smooth muscle cells.

AIM: The current study aimed to examine miR-145's contribution to thoracic aortic dissection (AD) development by modulating the biological functions of vascular smooth muscle cells (VSMCs). METHODS: The concentration of circulating miR-145 was determined in patients with AD and healthy controls using quantitative polymerase chain reaction (qPCR). Aortic specimens were obtained from both individuals with Stanford type A AD undergoing surgical treatment and deceased organ donors (serving as controls) whose causes of death were nonvascular diseases. Then, qPCR and fluorescence in situ hybridization were applied to assess miR-145 amounts and location, respectively. Furthermore, qPCR and immunoblot were employed to determine SMAD3 (the target gene of miR-145, involved in the TGF-ß pathway) amounts at the gene and protein levels, respectively. Moreover, in vitro transfection of VSMCs with miR-145 mimics or inhibitors was conducted. Finally, the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Transwell assay and flow cytometry were employed for detecting VSMC proliferation, migration, and apoptosis, respectively. RESULTS: The amounts of miR-145 in plasma and aortic specimens were markedly reduced in the AD group in comparison with control values (P < .05). miR-145 was mostly located in VSMCs. Proliferation and apoptosis of VSMCs were significantly induced in vitro by the downregulation of miR-145. Also, miR-145 modulated SMAD3 expression. CONCLUSIONS: miR-145 was found to be downregulated in patients with AD, which induced the proliferation, migration, and apoptosis of VSMCs by targeting SMAD3. This suggested the involvement of miR-145 in the pathogenesis of AD.

Calcitonin gene-related peptide facilitates sensitization of the vestibular nucleus in a rat model of chronic migraine.

BACKGROUND: Vestibular migraine has recently been recognized as a novel subtype of migraine. However, the mechanism that relate vestibular symptoms to migraine had not been well elucidated. Thus, the present study investigated vestibular dysfunction in a rat model of chronic migraine (CM), and to dissect potential mechanisms between migraine and vertigo. METHODS: Rats subjected to recurrent intermittent administration of nitroglycerin (NTG) were used as the CM model. Migraine- and vestibular-related behaviors were analyzed. Immunofluorescent analyses and quantitative real-time polymerase chain reaction were employed to detect expressions of c-fos and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and vestibular nucleus (VN). Morphological changes of vestibular afferent terminals was determined under transmission electron microscopy. FluoroGold (FG) and CTB-555 were selected as retrograde tracers and injected into the VN and TNC, respectively. Lentiviral vectors comprising CGRP short hairpin RNA (LV-CGRP) was injected into the trigeminal ganglion. RESULTS: CM led to persistent thermal hyperalgesia, spontaneous facial pain, and prominent vestibular dysfunction, accompanied by the upregulation of c-fos labeling neurons and CGRP immunoreactivity in the TNC (c-fos: vehicle vs. CM = 2.9 ± 0.6 vs. 45.5 ± 3.4; CGRP OD: vehicle vs. CM = 0.1 ± 0.0 vs. 0.2 ± 0.0) and VN (c-fos: vehicle vs. CM = 2.3 ± 0.8 vs. 54.0 ± 2.1; CGRP mRNA: vehicle vs. CM = 1.0 ± 0.1 vs. 2.4 ± 0.1). Furthermore, FG-positive neurons was accumulated in the superficial layer of the TNC, and the number of c-fos+/FG+ neurons were significantly increased in rats with CM compared to the vehicle group (vehicle vs. CM = 25.3 ± 2.2 vs. 83.9 ± 3.0). Meanwhile, CTB-555+ neurons dispersed throughout the VN. The structure of vestibular afferent terminals was less pronounced after CM compared with the peripheral vestibular dysfunction model. In vivo knockdown of CGRP in the trigeminal ganglion significantly reduced the number of c-fos labeling neurons (LV-CGRP vs. LV-NC = 9.9 ± 3.0 vs. 60.0 ± 4.5) and CGRP mRNA (LV-CGRP vs. LV-NC = 1.0 ± 0.1 vs. 2.1 ± 0.2) in the VN, further attenuating vestibular dysfunction after CM. CONCLUSIONS: These data demonstrates the possibility of sensitization of vestibular nucleus neurons to impair vestibular function after CM, and anti-CGRP treatment to restore vestibular dysfunction in patients with CM.

STAT3-induced upregulation of lncRNA CASC11 promotes the cell migration, invasion and epithelial-mesenchymal transition in hepatocellular carcinoma by epigenetically silencing PTEN and activating PI3K/AKT signaling pathway.

Accumulating evidence suggest that long noncoding RNAs (lncRNAs) are dysregulated in various tumors and serve as crucial regulators in biological processes. Based on The Cancer Genome Atlas (TCGA) database, upregulation of CASC11 was associated with the low overall survival rate of patients with Hepatocellular carcinoma (HCC). However, the function and mechanism of lncRNA CASC11 in the progression of HCC remain unclear. Therefore, we further analyzed the expression pattern and biological role of CASC11 in HCC. CASC11 was found to be overexpressed in HCC tissues and cell lines and predicted a poor prognosis. Loss of CASC11 function efficiently suppressed cell migration, invasion and epithelial-mesenchymal transition (EMT). The mechanism which led to the upregulation of CASC11 was investigated. CASC11 was found to be activated by the transcription factor STAT3. Mechanically, the enhancer of zeste homolog 2 (EZH2) was found to be a binding partner of CASC11. Moreover, CASC11 epigenetically silenced PTEN by binding with EZH2. Finally, rescue assays were conducted to make confirmation. The present results revealed that CASC11 may be potential therapeutic target in HCC.

Upregulation of miR-146a-5p is associated with increased proliferation and migration of vascular smooth muscle cells in aortic dissection.

BACKGROUND: This study aimed to investigate whether miR-146a-5p was involved in the pathogenesis of thoracic aortic dissection (AD) via regulating the biological function of vascular smooth muscle cells (VSMCs). METHODS: Circulating miR-146a-5p level was measured by quantitative polymerase chain reaction (qPCR) in AD patients and healthy controls. Human dissected aortic samples were obtained from patients with thoracic AD Stanford type A undergoing surgical repair, and normal control samples were from organ donors who died from nonvascular diseases. The expression level of miR-146a-5p was detected using qPCR in each sample. The expression of SMAD4, which is involved in the TGF-ß pathway and indicated as the target gene of miR-146a-5p, was measured by qPCR and Western blot analysis at the mRNA level and protein level, respectively. Subsequently, VSMCs were transfected with miR-146a-5p mimics or inhibitors in vitro. VSMC proliferation and migration were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assay, respectively. Flow cytometry was used to identify apoptosis. The expression of SMAD4 in VSMCs was determined using qPCR and Western blot analysis. RESULTS: Plasma level of miR-146a-5p is significantly higher in the AD group as compared with the control group. The expression of miR-146a-5p was significantly upregulated in dissected aorta compared with controls (P < 0.05). The overexpression of miR-146a-5p significantly induced VSMC proliferation and migration in vitro. CONCLUSIONS: The expression of SMAD4 was modulated by miR-146a-5p. miR-146a-5p induced VSMC proliferation and migration through targeting SMAD4 and hence might be potentially involved in the development of AD.

Outcomes of hybrid procedure for type B aortic dissection with an aberrant right subclavian artery.

OBJECTIVE: To report our single-center experience of the hybrid procedure for type B aortic dissection (TBAD) with an aberrant right subclavian artery (ARSA) and the early to midterm outcomes in these patients. METHODS: From December 2011 to February 2016, 16 patients (12 males; median age, 51 years; range, 40-66 years) underwent thoracic endovascular aortic repair and extraanatomic bypass hybrid procedure for TBAD with an ARSA in our center. Demographics, coexisting medical conditions, imaging features, operation details, and follow-up outcomes of these patients were collected retrospectively and analyzed. RESULTS: Duration from onset to hybrid procedure ranged from 5 to 57 days, with a median duration of 17 days. The median duration of stay in the intensive care unit and duration of in-hospital stay was 126 hours (range, 14-450 hours) and 21 days (range, 11-31 days), respectively. The overall technique success rate was 100%. No perioperative death, major stroke, or spinal cord ischemia was registered. Immediate type Ia endoleak was detected in three patients (18.8%) and immediate type II endoleak was detected in one patient (6.3%). One access-related complication occurred, which was a femoral artery pseudoaneurysm requiring compression bandage. Brachial plexus injury was observed in two patients (12.5%) with weakness of the upper extremity. The median follow-up was 33 months (range, 11-59 months). During follow-up, a retrograde type A aortic dissection was found in one patient (6.3%) 3 months after procedure. The occlusion of left common carotid artery to left subclavian artery bypasses were confirmed by computed tomography angiography in two patients (12.5%). They were left untreated for no symptoms. Reintervention was required in one patient (6.3%) for persistent type II endoleak by using Amplatzer plugs to seal the origin of the ARSA 20 months after the operation. There was no recorded death or stroke during the study period. CONCLUSIONS: Our limited experience demonstrates that a hybrid procedure is a viable and relatively safe treatment strategy for patients with TBAD and an ARSA. A larger series of cases with a longer follow-up is needed to substantiate these results.