Successful endovascular management for spontaneous hemothorax in a patient with neurofibromatosis Type1: A case report and review.

INTRODUCTION AND IMPORTANCE: Neurofibromatosis Type 1 (NF1) is a rare autosomal dominant genetic disorder that affects multiple organs and systems, including the nervous system, integumentary system, and connective tissues. Spontaneous hemothorax occurs infrequently in patients with NF1 and is associated with high fatality rates. However, it is commonly overlooked or misdiagnosed. CASE PRESENTATION: We present the case of a 29-year-old woman with NF1 who complained of chest pain and was detected with hemothorax on radiographic examination. No bleeding sites were identified following thrombectomy. The patient's condition deteriorated with conservative treatment over nine days, posing a potentially life-threatening risk. After a diagnostic evaluation using computerized tomography angiography (CTA) and digital subtraction angiography (DSA) of the neck vasculature, the patient was diagnosed with spontaneous rupture of the vertebral artery (VA) and subclavian artery (SuA) aneurysm. Following a multidisciplinary discussion and extensive investigations, the patient underwent successful endovascular treatment. A VIABAHN covered stent was implanted in the left SuA to overlay the emergent orifice. The endovascular treatment challenge due to the inaccessible of the proximal of left VA. To prevent retrograde flow into the VA aneurysm, the coils were used to embolize the left VA via the right vertebral artery-basilar artery (VA-BA) passage. The patient was alive at the 5-year follow-up without further complications. CLINICAL DISCUSSION: The CTA examination led to the diagnosis of vascular rupture due to NF1, and endovascular treatment was performed to occlude the vascular lumen. There have been no recurrences during the five-year follow-up period. CONCLUSION: Vasculopathy is the second leading cause of death in patients with NF1 after malignancy. Early diagnosis of spontaneous hemothorax in patients with NF1 is crucial, as misdiagnosis can result in missed treatment opportunities. CTA plays a vital role in preliminarily diagnosing the cause of spontaneous hemothorax, while endovascular treatment offers a new therapeutic option for such patients.

A new noninvasive and patient-specific hemodynamic index for the severity of renal stenosis and outcome of interventional treatment.

Renal arterial stenosis (RAS) often causes renovascular hypertension, which may result in kidney failure and life-threatening consequences. Direct assessment of the hemodynamic severity of RAS has yet to be addressed. In this work, we present a computational concept to derive a new, noninvasive, and patient-specific index to assess the hemodynamic severity of RAS and predict the potential benefit to the patient from a stenting therapy. The hemodynamic index is derived from a functional relation between the translesional pressure indicator (TPI) and lumen volume reduction (S) through a parametric deterioration of the RAS. Our in-house computational platform, InVascular, for image-based computational hemodynamics is used to compute the TPI at given S. InVascular integrates unified computational modeling for both image processing and computational hemodynamics with graphic processing unit parallel computing technology. The TPI-S curve reveals a pair of thresholds of S indicating mild or severe RAS. The TPI at S = 0 represents the pressure improvement following a successful stenting therapy. Six patient cases with a total of 6 aortic and 12 renal arteries are studied. The computed blood pressure waveforms have good agreements with the in vivo measured ones and the systolic pressure is statistical equivalence to the in-vivo measurements with p < .001. Uncertainty quantification provides the reliability of the computed pressure through the corresponding 95% confidence interval. The severity assessments of RAS in four cases are consistent with the medical practice. The preliminary results inspire a more sophisticated investigation for real medical insights of the new index. This computational concept can be applied to other arterial stenoses such as iliac stenosis. Such a noninvasive and patient-specific hemodynamic index has the potential to aid in the clinical decision-making of interventional treatment with reduced medical cost and patient risks.

Red blood cell distribution width-to-albumin ratio is associated with all-cause mortality in cancer patients.

BACKGROUND: Cancer causes a serious health burden on patients worldwide. Chronic low-level inflammation plays a key role in tumorigenesis and prognosis. However, the role of the red blood cell distribution width (RDW)-to-albumin (RA) ratio in cancer mortality remains unclear. METHODS: In this retrospective cohort study, we collected clinical information from cancer patients from the Medical Information Mart for Intensive Care III (MIMIC-III) version 1.4 database and then calculated RA by dividing RDW by albumin concentration. The primary outcome was 30 days mortality, while secondary outcomes were 90 days and 1 year mortality. Next, we adopted Cox regression models to calculate hazard ratios (HR) together with 95% confidence intervals (CI) for all-cause mortalities associated with the RA ratio. RESULTS: For 30 days mortality, the HR (95% CI) for the high RA ratio (≥5.51) was 2.17 [95CI% (1.87-2.51); p = <0.0001], compared with the low RA ratio (<5.51). In Model 2, we adjusted sex and age and obtained HR (95% CI) of 2.17 [95CI% (1.87-2.52); p = <0.0001] for the high RA ratio (≥5.51) group, compared to that in the low RA ratio (<5.51). In Model 3, adjusting for age, sex, anion gap, hematocrit, white blood cell count, congestive heart failure, SOFA, liver disease, and renal failure resulted in HR (95% CI) of 1.74 [95CI% (1.48-2.04); p = <0.0001] for the high RA ratio (≥5.51) relative to the low RA ratio (<5.51). We also analyzed common diseases in cancer patients but found no significant association. CONCLUSION: To the best of our knowledge, this is the first study demonstrating that increased RA ratio is independently associated with increased all-cause mortality in cancer patients.

Association Between Red Blood Cell Distribution Width-to-Albumin Ratio and Prognosis of Patients with Aortic Aneurysms.

OBJECTIVE: Red blood cell distribution width (RDW) is a predictor of adverse outcomes in aortic aneurysms. Recent recommendations suggest that combining RDW with other biomarkers could yield better results. We, therefore, propose evaluating the biomarker of vascular aging, albumin with RDW to predict the risk of aortic aneurysms. This study aims to explore whether the combination of RDW with albumin can effectively predict the prognosis of aortic aneurysm patients. METHODS: This retrospective cohort study was conducted among adults (age >18) with aortic aneurysms in the Medical Information Mart for Intensive Care Database III V1.4 (MIMIC-III). RAR was measured according to the red blood cell distribution width and albumin. The primary outcome was the 30-day mortality rate, and the secondary outcome was the 90-day and one-year mortality rates. Estimation of hazard ratios (HR) was obtained from Cox regression models for all-cause mortality related to red cell distribution width-to-albumin ratio (RAR) values. RESULTS: In total, 312 patients were involved, with an average age of 74.9 ± 10.9 years and an average RAR value of 5.4 ± 1.6 mL/g. In 30 days for all-cause mortality, the HR (95% CI) in the highest RAR group (>5.8 mL/g) in tertiles was 2.54 (1.25, 5.14) in the unadjusted model, with a significant difference compared with the reference group (P < 0.05). After adjusting for race, gender and age, there was still a correlation (P < 0.05), and the HR (95% CI) was 2.51 (1.23, 5.10). Further adjustment of possible covariates showed similar correlation in model 3 (P < 0.05), and HR (95% CI) was 2.66 (1.17, 6.01). Multivariable logistic regression shows that RAR is an independent risk factor for the outcome of aortic aneurysms after adjusting the covariates. In the subgroup analysis, we analyzed the patient's complications, and no significant interaction was observed. CONCLUSION: RAR is a risk factor for patients with aortic aneurysms. However, more in-depth research is warranted to further analyze and substantiate our findings on the role of RAR in aortic aneurysm patients.

Effect of miR-126 on the Proliferation and Migration of Vascular Smooth Muscle Cells in Aortic Aneurysm Mice Under PI3K/AKT/mTOR Signaling Pathway.

This paper is to investigate the expression changes of Phosphatidylinositol-3 Kinase (PI3K), protein kinase B (AKT), and Mammalian Target of Rapamycin (mTOR) in Vascular Smooth Muscle Cells (VSMCs) of aortic aneurysm mice, and to analyze the mechanism of VSMCs proliferation and migration. Aortic VSMCs cells were cultured using BALB/c mice as the research object. VSMCs were identified using artificial intelligence-based digital microscopy equipment, and liposome-transfected VSMCs experiments were performed. Real-time PCR was used for the mRNA expression levels of miR-126 and Phosphatase and Tensin Homolog (PTEN). Western blot was used for the protein expression levels of PTEN, PI3K, AKT, and mTOR. The cultured cells were identified as mouse VSMCs using digital microscopes based on artificial intelligence. Compared with the normal group, the expression of miR-126 and PTEN mRNA in the model group were significantly increased and reduced, respectively. Compared with the model group, the expression level of miR-126 and PTEN mRNA in the inhibitor group were significantly reduced and increased, respectively. Compared with the model group, the expression of miR-126 and PTEN mRNA in the ursolic acid group was significantly reduced and increased, respectively. After liposome transfection, compared with the normal group, the expression of PTEN protein in the model group was significantly reduced, and the expression of PI3K protein was significantly increased. Compared with the model group, the expression of PTEN protein was significantly increased and the expression of PI3K protein was significantly decreased in the transfection group. Compared with the control group, the expression of PI3K, AKT and mTOR protein in the model group was significantly increased. Compared with the model group, the expression of PI3K, AKT, and mTOR protein in the ursolic acid group was significantly reduced. The expressions of PI3K, AKT and mTOR protein in PI3K inhibitor group and AKT inhibitor group were significantly reduced. In conclusion, ursolic acid can inhibit the proliferation and migration of VSMCs in aortic aneurysm mice through the miR-126/PTEN/PI3K/AKT/mTOR signaling pathway. Furthermore, PTEN gene and miR-126 negatively regulate PI3K/AKT/mTOR and PTEN/PI3K/AKT/mTOR signaling pathway, respectively .

Clinical efficacy of one-stage thrombus removal via contralateral femoral and ipsilateral tibial venous access for pharmacomechanical thrombectomy in entire-limb acute deep vein thrombosis.

OBJECTIVE: In the present study, we compared the early results between different approaches for pharmacomechanical thrombectomy (PMT) in the treatment of entire-limb acute deep vein thrombosis (DVT). METHODS: The present retrospective cohort study included patients with entire-limb acute DVT who had undergone PMT from January 2016 to March 2019 at two independent vascular centers. At the first center (Renji Hospital), the vascular surgeons used contralateral femoral venous access or ipsilateral tibial venous access (CFVA/ITVA). All consecutive patients with entire-limb acute DVT had undergone PMT through CFVA/ITVA at the first center. At the second center (Affiliated Hangzhou First People's Hospital), the vascular surgeons had conducted PMT using the traditional approach via ipsilateral popliteal venous access (IPVA). All consecutive patients had undergone PMT through IPVA at the second center. The primary endpoint was the incidence of post-thrombotic syndrome (PTS). The secondary endpoints included thrombus removal grade, venous primary patency rate, and the incidence of moderate-to-severe PTS. RESULTS: A total of 73 patients were enrolled in the present study, including 37 patients with CFVA/ITVA at the first center and 36 patients with IPVA at the second center. No significant difference was detected between the two groups in age, gender, onset time, affected limb, or risk factors. The proportion of patients who had undergone catheter-directed thrombolysis was significantly lower in the CFVA/ITVA group than in the IPVA group (P = .010). Thrombus removal grade III was achieved more often in the CFVA/ITVA group than in the IPVA group (P = .007). The PTS incidence was significantly lower in the CFVA/ITVA group than in the IPVA group (P = .043). The thrombus removal grade and access type were independent factors associated with the development of PTS. Patients with complete thrombus removal (grade III) and CFVA/ITVA had a significantly lower incidence of PTS. CONCLUSIONS: PMT can increase the thrombus clearance rate, reduce the requirement for subsequent catheter-directed thrombolysis, and, potentially, decrease the incidence of PTS using CFVA/ITVA instead of traditional IPVA in the treatment of entire-limb acute DVT.

Elevation of hypertonicity­induced protein NFAT5 promotes apoptosis of human umbilical vein endothelial cells through the NF­κB pathway.

Abdominal aortic aneurysm (AAA) is a great threat to the health of elder (>50 years old) individuals. High salt intake is considered to raise the risk of AAA but the underlying mechanism remains to be elucidated. As endothelial dysfunction in the abdominal aorta is strongly associated with AAA, the present study hypothesized that high salt led to AAA by inducing apoptosis of endothelial cells. The present study verified that hypertonic medium with excess sodium chloride induced apoptosis of human umbilical vein endothelial cells (HUVECs), a commonly used cell model to study aortic endothelial cells. Further mechanism studies suggested that hypertonic conditions elevated the expression of nuclear factor of activated T cells 5 (NFAT5) and a high level of NFAT5 was capable of inducing apoptosis of HUVECs. In the investigation of downstream signals of NFAT5, it was identified that either hypertonic conditions or NFAT5 overexpression promoted the activity of NF­κB signaling pathway and subsequently suppressed the expression of anti­apoptotic protein Bcl­2. Thus, the present study demonstrated a novel mechanism by which high salt induced apoptosis of endothelial cells by enhancing the NFAT5­NF­κB signaling pathway. These findings will extend our knowledge about the pathogenesis of AAA and provide potential drug targets for the treatment of AAA.

Zinc Finger E-Box Binding Protein 2 (ZEB2) Suppress Apoptosis of Vascular Endothelial Cells Induced by High Glucose Through Mitogen-Activated Protein Kinases (MAPK) Pathway Activation.

BACKGROUND Hyperglycemia has been confirmed to damage endothelial function of vascular and microvascular. The regulation of zinc finger E-box binding protein 2 (ZEB2) on vascular endothelial cells (VECs) is reported rarely. Our study investigates the role of ZEB2 on the apoptosis of VECs induced by high glucose through MAPK pathway. MATERIAL AND METHODS Downregulated and upregulated expression of ZEB2 in human umbilical vein endothelial cells (HUVECs) were performed by plasmids transfection. HUVECs are respectively treated with different concentrations of glucose (5.5 mM, 33 mM). The expression of mRNA and protein were detected by real-time quantified PCR and western blotting. Apoptotic cells were measured by flow cytometry. Proliferation and migration of HUVECs were detected by MTT assay and wound healing assay. RESULTS The apoptosis of HUVECs detected by flow cytometry and western blot revealed that ZEB2 overexpression distinctly suppressed the apoptosis of HUVECs induced by high glucose. ZEB2 overexpression promoted the proliferative and migration activity of HUVECs. Besides, ZEB2 overexpression specifically accelerated the phosphorylation level of JNK, and suppressed the apoptosis and promoted the proliferative of VECs via JNK pathway. CONCLUSIONS ZEB2 suppress apoptosis of VECs induced by high glucose through MAPK pathway activation, which provides a novel insight and therapeutic target for endothelial injury.

microRNA-23b suppresses epithelial-mesenchymal transition (EMT) and metastasis in hepatocellular carcinoma via targeting Pyk2.

Numerous microRNAs (miRNAs) have been shown to play important roles in various cancers, including hepatocellular carcinoma (HCC). However, the functions and mechanisms of the miRNAs involved in HCC progress and metastasis still remain unknown. We downloaded the normalized data of microRNA expression profiling of HCC comparing primary tumor with lung metastasis from GEO database (GSE26323), and gain a group of metastasis-related candidate miRNAs. Among the candidate miRNAs, we focused on miR-23b for further study. The association of metastasis-related miR-23b with survival was also explored. Furthermore, the effects of miR-23b on biological role in HCC were demonstrated by MTT proliferation assay, wound healing and migration assay and the EMT related markers was analyzed by Western blot. Potential target genes of miR-23b were predicted using TargetScan and PicTar and confirmed by luciferase activity assay. A rescue experiment was performed to verify whether the function of miR-23b was exerted via regulation of its target. Our results showed that miR-23b expression was significantly decreased in HCC tissues, which was more importantly, positively correlated to the intrahepatic metastasis of HCC. Meanwhile, patients with low miR-23b expression had significantly poorer prognosis. Overexpression of miR-23b could inhibit MHCC97L cell proliferation, migration, invasion and regulate the expression of MMPs and EMT-associated genes. Moreover, Pyk2, one of the crucial regulators of EMT, was identified as a direct target of miR-23b. In addition, the inhibitory effects of miR-23b overexpression on the metastasis could be restored by Pyk2 overexpression. This study revealed that miR-23b was a tumor suppressor which may regulate HCC migration and invasion by targeting Pyk2 via regulation of EMT, implicating a potential prognostic biomarker and therapeutic target for HCC treatment.