Maresin1 Promotes M2 Macrophage Polarization Through Peroxisome Proliferator-Activated Receptor-γ Activation to Expedite Resolution of Acute Lung Injury.

BACKGROUND: Acute lung injury (ALI), manifested by progressive hypoxemia and respiratory distress, is associated with high morbidity and mortality, which lacks the effective therapies in clinics. Our previous studies demonstrated that maresin1 (MaR1), a specialized proresolving mediator, could effectively mitigate the inflammation of lipopolysaccharide (LPS)-induced ALI. However, whether MaR1 impacts the macrophage polarization to alleviate ALI remains unclear. Our study explored the effects and underlying mechanisms of MaR1 on the macrophage phenotypes in ALI. MATERIAL AND METHODS: Male BALB/c mice were subjected to endotracheal instillation of LPS to induce ALI and then intravenously injected with MaR1 or normal saline. Intraperitoneal administration of peroxisome proliferator-activated receptor-γ (PPAR-γ) inhibitor GW9662 was given 30 mins before MaR1. We measured the pathohistologic changes, pulmonary edema, inflammatory cytokines, and the flow cytometry of macrophage phenotypes. RESULTS: Our results illustrated that MaR1 ameliorated lung injury and increased monocyte or macrophage recruitment and the release of anti-inflammatory cytokines. The flow cytometry showed that MaR1 promoted polarization of CD11c-CD206+ (M2) macrophages and inhibited polarization of CD11c+CD206- (M1) macrophages. Besides, the western blotting revealed that MaR1 increased the expression of PPAR-γ. The pretreatment with PPAR-γ antagonist GW9662 could significantly suppress the polarization of M2 macrophages and antagonize the protective effects of MaR1 on LPS-stimulated ALI. CONCLUSIONS: MaR1 was able to promote M2 macrophage polarization by reversing LPS-mediated PPAR-γ inhibition, thereby expediting the recovery of LPS-stimulated ALI.

The myodural bridge complex defined as a new functional structure.

PURPOSE: The connective tissue between suboccipital muscles and the cervical spinal dura mater (SDM) is known as the myodural bridge (MDB). However, the adjacent relationship of the different connective tissue fibers that form the MDB remains unclear. This information will be highly useful in exploring the function of the MDB. METHODS: The adjacent relationship of different connective tissue fibers of MDB was demonstrated based upon three-dimensional visualization model, P45 plastinated slices and histological sections of human MDB. RESULTS: We found that the MDB originating from the rectus capitis posterior minor muscle (RCPmi), rectus capitis posterior major muscle (RCPma) and obliquus capitis inferior muscle (OCI) in the suboccipital region coexists. Part of the MDB fibers originate from the ventral aspect of the RCPmi and, together with that from the cranial segment of the RCPma, pass through the posterior atlanto-occipital interspace (PAOiS) and enter into the posterior aspect of the upper cervical SDM. Also, part of the MDB fibers originate from the dorsal aspect of the RCPmi, the ventral aspect of the caudal segment of the RCPma, and the ventral aspect of the medial segment of the OCI, enter the central part of the posterior atlanto-axial interspace (PAAiS) and fuse with the vertebral dura ligament (VDL), which connects with the cervical SDM. CONCLUSIONS: Our findings prove that the MDB exists as a complex structure which we termed the 'myodural bridge complex' (MDBC). In the process of head movement, tensile forces could be transferred possibly and effectively by means of the MDBC. The concept of MDBC will be beneficial in the overall exploration of the function of the MDB.

Coil Embolization for Persistent Thoracic False Lumen of Type B Aortic Dissection after Thoracic Endovascular Aortic Repair.

BACKGROUND: The natural history of the thoracic false lumen after coil embolization for type B aortic dissection (TBAD) treated by previous thoracic endovascular aortic repair (TEVAR) remains a matter of debate. The aim of this study is to assess the efficacy of coil embolization in promoting thoracic aortic remodeling of TBAD with persistent thoracic false lumen after TEVAR. METHODS: Between January 2015 and December 2016, 7 consecutive TBAD patients with persistent thoracic false lumen post-TEVAR underwent coil embolization, either isolated (3 with maximum thoracic aortic diameter <55 mm) or combined with adjunctive procedure(s) specifically for distal re-entry tears (4 with thoracic aneurysmal aortic dissection ≥55 mm in diameter). Pre- and postcoiling computer tomography angiography (CTA) images were used to evaluate aortic remodeling via false lumen thrombosis status and maximum thoracic aorta diameter. RESULTS: Procedures were performed successfully in all patients, without intraoperative complications or 30-day mortality. Two dissection-related deaths occurred after hospital discharge, yielding a 6-month mortality of 28.6%. Six patients had surveillance CTA images available for analyses at median 11.2 months (range 5.6-23.5) of follow-up. Thoracic aortic shrinkage and completely thrombosed thoracic false lumen were seen in 1 patient (16.7%); thoracic aortic stabilization albeit with persistent blood flow along the false lumen below or even more proximal to the embolization in 4 patients (66.7%); and continued thoracic aortic growth and aortoesophageal fistula proximal to the embolized false lumen in 1 patient. CONCLUSIONS: In this retrospective single center experience, the efficacy of coil embolization in promoting thoracic aortic remodeling of TBAD with persistent thoracic false lumen post-TEVAR appears to be limited, especially in patients with thoracic aneurysmal aortic dissection. Further studies are warranted to inform the optimal treatment strategy.

Novel Morphological Features for Prediction of Distal Thoracic Aortic Enlargement after Thoracic Endovascular Aortic Repair of DeBakey IIIb Aortic Dissection.

BACKGROUND: Identifying the risk factors predisposing to aortic enlargement after thoracic endovascular aortic repair (TEVAR) is needed for DeBakey IIIb aortic dissection. The aim of the study is to assess the novel morphological features for DeBakey IIIb aortic dissection in predicting distal thoracic aortic enlargement after TEVAR. METHODS: Sixty-seven patients who underwent TEVAR for DeBakey IIIb aortic dissection between January 2011 and December 2013 at our center were divided based on preoperative computer tomography angiography (CTA) features into 3 groups: I (n = 27) and III (n = 9), with true and false lumen, respectively, coursing closely along thoracic vertebral bodies and II, spiral configuration (n = 31). Distal thoracic aortic enlargement was determined using preoperative and postoperative CTA images. RESULTS: At median 12.2 (interquartile range, 4.3-26.6) months, 12 patients developed distal thoracic aortic enlargement, with estimated cumulative incidence tending to increase from categories I to III (P for trend < 0.01). Categories II and III versus I had more frequently concave location of primary entry tear (P < 0.01), larger dissection length and height index (L/Hi) (P = 0.05), and greater number of abdominal small branches involved preoperatively (P = 0.03), with otherwise similar baseline characteristics; and significantly greater total aortic diameter increase and lower false lumen regression up to 24 months, and lower true lumen expansion up to 12 months. In multivariable regression analysis, categories II and III were independently associated with distal thoracic aortic enlargement (hazard ratio, 19.95 [95% confidence interval, 2.14-186.09]; 41.23 [3.61-470.22], respectively) after adjustment for Society of Vascular Surgery score, preoperative maximum total aortic diameter, L/Hi, and number of abdominal small branches involved preoperatively. CONCLUSIONS: The CTA-based morphological features described in this study might improve preoperative risk stratification of DeBakey IIIb aortic dissection, with categories II and III having higher risk of distal thoracic aortic enlargement after TEVAR.

Preoperative thoracic false lumen branches relate to aortic remodeling after thoracic endovascular aortic repair for DeBakey IIIb aortic dissection.

OBJECTIVE: This study evaluated the association between thoracic false lumen branches (TFLBs; dissected thoracic branches fed by a false lumen) and distal thoracic aortic enlargement (DTAE) after thoracic endovascular aortic repair (TEVAR) for DeBakey IIIb aortic dissection. METHODS: We retrospectively analyzed the records of 67 patients with DeBakey IIIb dissection initially treated with TEVAR between January 2011 and December 2013. Preoperative and postoperative computed tomography angiography images were reviewed to evaluate the number of preoperative TFLBs and aortic diameter change after TEVAR. Patients were stratified into two groups by the estimated optimal cutoff value of preoperative TFLBs for the prediction of DTAE: group A (n = 28), preoperative TFLBs ≥8; group B (n = 39), preoperative TFLBs <8. The diameter changes over time were modeled by mixed models of repeated data. Multivariable Cox regression analysis was used to assess the independent association between preoperative TFLBs and DTAE after TEVAR. RESULTS: Baseline demographics, clinical features, and devices implanted were largely similar between the two groups. Group A had more preoperative abdominal false lumen branches (7 [4-8] vs 4 [1-6]; P = .02) and a greater proportion of preoperative patent thoracic false lumen (83.9% vs 66.7%; P = .04). Twelve patients experienced DTAE during a median imaging follow-up period of 12.2 months (interquartile range, 4.3-26.6 months). Log-rank testing revealed a significant increase in cumulative estimated proportion with DTAE in group A (P < .01). The maximum thoracic aortic diameter decreased significantly in group B (P < .01) but not in group A. The overall change in the maximum thoracic aortic diameter was statistically different between the two groups (P < .01). Each group exhibited a significant increase in true lumen diameter and a significant decrease in false lumen diameter postoperatively. However, a lower degree of false lumen regression in group A was detected compared with group B (P = .03). Multivariable analysis identified that preoperative TFLBs were independently associated with DTAE after TEVAR (hazard ratio [for one increase], 1.46; 95% confidence interval, 1.20-1.77) after adjustment for gender, hyperlipidemia, length of dissected aorta and height index, preoperative abdominal false lumen branches, and preoperative false lumen status of thoracic aorta. CONCLUSIONS: Preoperative TFLBs are independently associated with DTAE after TEVAR in DeBakey IIIb aortic dissection. Long-term follow-up is necessary to further verify the preliminary finding.

Thoracic Aorta Dimension Changes During Systole and Diastole: Evaluation with ECG-Gated Computed Tomography.

BACKGROUND: This study was conducted to characterize the differences in the dimensions between systole and diastole in thoracic aorta in Chinese population with electrocardiogram (ECG)-gated multidetector computed tomography angiography (CTA) scans. METHODS: The CTAs of 56 patients (mean age 58.2 ± 17.9 years; 42 men, 14 women) both in systole and diastole were obtained on a 64-slice ECG-gated multidetector CT scanner. Four anatomic levels of the thoracic aorta were selected for analysis (Level A: 1 cm proximal to the innominate artery; Level B: 1 cm distal to the left common carotid artery; Level C: 1 cm distal to the left subclavian artery; and Level D: 10 cm distal to the left subclavian artery). On each level, the maximal and the minimal diameters were measured both in systole and diastole. RESULTS: The paired sample t-test results showed a significant difference between the systolic and diastolic diameters in all individual subjects on every level. The diameter differences range between -1.7 mm (diastolic dimension is greater than systolic dimension) and 3.6 mm (systolic dimension is greater than diastolic dimension). The aortic diameters in diastolic phase are greater than in systolic phase in 18-22% subjects on different levels. A mean maximum diameter change of 2.68% (range -3.45% to 8.25%) and a mean minimum diameter change of 2.71% (range -5.05% to 8.38%) were found at Level A; a maximum diameter change of 2.89% (range -4.5% to 13.3%) and a minimum diameter change of 2.37% (range -5.2% to 14.9%) were found at Level B; a maximum diameter change of 2.81% (range -6.02% to 10.85%) and a minimum diameter change of 2.92% (range -7.14% to 9.62%) were found at Level C; and a maximum diameter change of 3.08% (range -1.76% to 10.36%) and a minimum diameter change of 2.93% (range -2.37% to 11.9%) were found at Level D. CONCLUSIONS: Our study verifies that the dimensional differences in thoracic aorta between systolic and diastolic phase are significant. But the pulsatility of thoracic aorta in Chinese population might be different from published literature.

A Novel Endovascular Double-Disc Implant for Sealing Intimal Tears in Aortic Dissection.

Postdissection thoracoabdominal aortic aneurysm incidence after thoracic endovascular aortic repair for type B aortic dissection is high, with residual distal tears being a major reason for persistent blood flow in the false lumen. The EndoPatch is an endovascular double-disc implant for sealing re-entry tears in aortic dissection, isolating blood flow in the false lumen and promoting thrombosis formation. Compared with conventional endovascular treatment techniques, this endovascular double-disc implant's small size and minimal working space requirements may reduce the risk of spinal ischemia and offer flexible vascular access. Although several barriers still impede this endovascular device's broad application, its innovative design, flexible vascular access, and streamlined surgical process make it a promising alternative for managing intimal tears in aortic dissection, either alone or as a supplementary method combined with conventional endovascular techniques. (Guo's Entry Tear Repair: The First in Man Study of Endopatch System; NCT04745039).

Experimental Study of the Propagation Process of Dissection Using an Aortic Silicone Phantom.

BACKGROUND: The mortality of acute aortic dissection (AD) can reach 65~70%. However, it is challenging to follow the progress of AD formation. The purpose of this work was to observe the process of dissection development using a novel tear-embedded silicone phantom. METHODS: Silicone phantoms were fabricated by embedding a torn area and primary tear feature on the inner layer. CT scanning and laser lightening were conducted to observe the variations in thickness and volume of the true lumen (TL) and false lumen (FL) during development. RESULTS: The model with a larger interlayer adhesion damage required a lower pressure to trigger the development of dissection. At the initiation stage of dissection, the volume of TL increased by 25.5%, accompanied by a 19.5% enlargement of tear size. The force analysis based on the change of tear size verified the deduction of the process of interlaminar separation from the earlier studies. CONCLUSIONS: The primary tear and the weakening adhesion of the vessel layers are key factors in AD development, suggesting that some forms of primary damage to the arterial wall, in particular, the lumen morphology of vessels with straight inner lumen, should be considered as early risk predictors of AD.

Co-expression Network Analysis Identifies Fourteen Hub Genes Associated with Prognosis in Clear Cell Renal Cell Carcinoma.

Renal cancer is a common genitourinary malignance, of which clear cell renal cell carcinoma (ccRCC) has high aggressiveness and leads to most cancer-related deaths. Identification of sensitive and reliable biomarkers for predicting tumorigenesis and progression has great significance in guiding the diagnosis and treatment of ccRCC. Here, we identified 2397 common differentially expressed genes (DEGs) using paired normal and tumor ccRCC tissues from GSE53757 and The Cancer Genome Atlas (TCGA). Then, we performed weighted gene co-expression network analysis and protein-protein interaction network analysis, 17 candidate hub genes were identified. These candidate hub genes were further validated in GSE36895 and Oncomine database and 14 real hub genes were identified. All the hub genes were up-regulated and significantly positively correlated with pathological stage and histologic grade of ccRCC. Survival analysis showed that the higher expression level of each hub gene tended to predict a worse clinical outcome. ROC analysis showed that all the hub genes can accurately distinguish between tumor and normal samples, and between early stage and advanced stage ccRCC. Moreover, all the hub genes were positively associated with distant metastasis, lymph node infiltration, tumor recurrence and the expression of MKi67, suggesting these genes might promote tumor proliferation, invasion and metastasis. Furthermore, the functional annotation demonstrated that most genes were enriched in cell-cycle related biological function. In summary, our study identified 14 potential biomarkers for predicting tumorigenesis and progression, which might contribute to early diagnosis, prognosis prediction and therapeutic intervention.

Long-Term Outcome of Chimney Technique Using a Balloon-Expandable Bare-Metal Stent to Preserve Supra-Arch Branches in Type B Aortic Dissection.

PURPOSE: This study was performed to investigate the long-term effect of chimney technique using balloon-expandable bare-metal stents (BMSs) to preserve the supra-arch branches in type B aortic dissection (TBAD). METHODS: Fifty patients with TBAD treated by thoracic endovascular aortic repair with the chimney technique (chTEVAR) using balloon-expandable BMSs from July 2009 to December 2013 were retrospectively assessed. Follow-up computed tomography angiography was performed to assess the postoperative outcomes. The primary end point was a persistent type Ia endoleak (ELIa). The secondary endpoints were chimney stent (CS)-based complications (stenosis, occlusion, fracture, or transposition), all-cause mortality, reintervention, and stroke. RESULTS: Fifty supra-arch branches (left common carotid artery, n = 11; left subclavian artery, n = 39) were preserved via the chimney technique with 50 balloon-expandable BMSs. The technical success rate was 100%. An immediate ELIa was discovered in 9 (18%) patients. The median survival duration during follow-up was 77.3 months. Five (10%) patients had a persistent ELIa; 3 of these patients had an immediate ELIa. Asymptomatic CS-based complications were found in 3 (6%) patients. The all-cause mortality rate was 8% (4/50); 2 deaths were aortic-related deaths. Five (10%) patients underwent a reintervention. During the estimated 36-month survival period, the survival rate, the rate of freedom from persistent ELIa, and the rate of freedom from reintervention were 93.87%, 89.48%, and 95.56%, respectively. CONCLUSIONS: The long-term outcomes showed that chTEVAR using balloon-expandable BMSs was safe and feasible for preservation of the supra-arch branches. Evaluation of more patients with a longer follow-up period is needed.

Preoperative thoracic false lumen branches are predictors of aortic enlargement after stent grafting for DeBakey IIIb aortic dissection.

OBJECTIVE: The study objective was to assess the effect of preoperative thoracic false lumen branches on thoracic aortic enlargement along the stent graft after thoracic endovascular aortic repair for DeBakey IIIb aortic dissection. METHODS: From January 2011 to December 2013, 67 patients who underwent thoracic endovascular aortic repair for DeBakey IIIb aortic dissection were retrospectively investigated. We assessed preoperative thoracic false lumen branches and diameter measurements at the level of the tracheal carina. Patients with a median follow-up of 12.2 months (interquartile range, 4.3-26.6 months) were categorized into 2 groups based on a receiver operating characteristic curve analysis: group A (preoperative thoracic false lumen branches ≥8, n = 28) and group B (preoperative thoracic false lumen branches <8, n = 39). Diameter changes over time were evaluated using a mixed model approach. A multivariate Cox regression analysis was used to study the influence of the preoperative thoracic false lumen branches on thoracic aortic enlargement along the stent graft. RESULTS: Six patients experienced thoracic aortic enlargement along the stent graft during follow-up (6 in group A, 0 in group B). The cumulative thoracic aortic enlargement along the stent-graft rate was higher in group A than in group B (log-rank P < .01). Diameter data showed significantly more reduction of the thoracic false lumen from preprocedure to 12 months in group B than in group A (change difference, 2.51; standard error, 0.99; P = .01). Complete false lumen thrombosis was more prominent in group B than in group A at each follow-up time point. After multivariate adjustment, preoperative thoracic false lumen branches were associated with thoracic aortic enlargement along the stent graft (hazard ratio, 2.92; 95% confidence interval, 1.06-8.01). CONCLUSIONS: Preoperative thoracic false lumen branches are a morphologic predictor of thoracic aortic enlargement along the stent graft in DeBakey IIIb aortic dissection after thoracic endovascular aortic repair.

Orientation and property of fibers of the myodural bridge in humans.

BACKGROUND CONTEXT: Studies over the past 20 years have revealed that there are fibrous connective tissues between the suboccipital muscles, nuchal ligament, and cervical spinal dura mater (SDM). This fibrous connection with the SDM is through the posterior atlanto-occipital or atlantoaxial interspaces and is called the myodural bridge (MDB). Researchers have inferred that the MDB might have important functions. It was speculated that the function of MDB might be related to proprioception transmission, keeping the subarachnoid space and the cerebellomedullary cistern unobstructed, and affecting the dynamic circulation of the cerebrospinal fluid. In addition, clinicians have found that the pathologic change of the MDB might cause cervicogenic or chronic tension-type headache. Previous gross anatomical and histologic studies only confirmed the existence of the MDB but did not reveal the fiber properties of the MDB. This is important to further mechanical and functional research on the MDB. PURPOSE: Multiple histologic staining methods were used in the present study to reveal the various origin and fiber properties of the MDB. Muscles and ligaments participating in forming the MDB at the posterior atlanto-occipital or atlantoaxial interspaces were observed, and the fiber properties of the MDB were confirmed. The present study provides a basis for speculating the tensile force values of the MDB on the SDM and a morphologic foundational work for exploring the physiological functions and clinical significances of the MDB. STUDY DESIGN: Anatomical and histologic analyses of suboccipital structures that communicate with the SDM at the posterior atlanto-occipital or atlantoaxial interspaces were carried out. METHODS: Multiple histologic staining methods were used to evaluate the histologic properties and composition of the MDB at the posterior atlanto-occipital or atlantoaxial interspaces in five formalin-fixed head-neck human specimens. RESULTS: The results show that the MDB traversing the atlanto-occipital interspace originated from the rectus capitis posterior minor (RCPmi). The MDB traversing the atlantoaxial interspace originated mainly from the RCPmi, rectus capitis posterior major, and obliquus capitis inferior. These fibers form the vertebral dural ligament in the atlantoaxial interspace and connect with SDM. The MDB is mainly formed by parallel running type I collagen fibers; thus, suboccipital muscle could pull SDM strongly through the effective force propagated by the MDB during head movement. CONCLUSIONS: Myodural bridge is mainly formed by parallel running type I collagen fibers; thus, it can transmit the strong pull from the diverse suboccipital muscles or ligaments during head movement. The results of the present study will serve as a basis for further biomechanical and functional MDB research.

Early and midterm outcomes of thoracic endovascular aortic repair (TEVAR) for acute and chronic complicated type B aortic dissection.

Thoracic endovascular aortic repair (TEVAR) in the current era has been chosen as a dominant and minimally invasive treatment for complicated aorta dissection. This study aimed to assess safety and feasibility of TEVAR in acute and chronic type B aortic dissection.Between January 2011 and December 2013, 85 patients with complicated type B aortic dissection undergoing TEVAR were divided into acute aortic dissection (AAD) (n = 60) group and chronic aortic dissection (CAD) group (n = 25). Computed tomography was used to evaluate postoperative changes in maximal aortic diameter and true and false lumen diameters at 3 levels during a mean follow-up period of 26.4 ±â€Š15.6 months.The technical success rate was 100%. In-hospital and 30-day rates of death were 3.3% in acute group and 0 in chronic group. Postdischarge rates of type I leak, type II leak, and retrograde type A dissection were 6.7%, 5.2%, and 3.4% (acute) and 0%, 4.0%, and 4.0% (chronic), respectively. The maximal aorta diameter remained stable in all the 3 levels in both acute and chronic group. The cumulative freedom from all-cause mortality at 3 years was similar in acute and chronic groups (89.5% vs 95.5%, P = .308). The cumulative freedom from aortic-related mortality was also not significantly different in the acute and chronic groups (92.8% vs 95.2%, P = .531). In the thoracic aorta, TEVAR treatment resulted in a significant increase in true lumen (TL) diameter and decrease in false lumen (FL). However, in the abdominal aorta, TEVAR did not lead to significant change in TL and FL diameters. The rates of complete thrombosis thoracic false lumens were better than that in the abdominal false lumen.TEVAR was a safe and effect therapy for complicated acute and chronic type B dissection with low early and mid-term mortality and morbidity.

Fenofibrate increases radiosensitivity in head and neck squamous cell carcinoma via inducing G2/M arrest and apoptosis.

Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/ or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.