A pyrimidine metabolism-related signature for prognostic and immunotherapeutic response prediction in hepatocellular carcinoma by integrating analyses.

BACKGROUND: Hepatocellular carcinoma (HCC), with discouraging morbidity and mortality, ranks as one of the most prevalent tumors worldwide. Pyrimidine metabolism is a critical process that regulates DNA and RNA synthesis in cells. It is imperative to investigate the significance of pyrimidine metabolism in liver cancer. METHODS: Transcriptome and clinical data were downloaded from the TCGA database and the GEO database. The genes related to pyrimidine metabolism were sourced from the MSigDB. The pyrimidine metabolism-related signature (PMRS) was constructed through Cox regression and Lasso regression and then verified in the external validation set from the ICGC database. Functional enrichment, immune infiltration analysis, drug sensitivity, and Immunophenoscore (IPS) were further implemented to predict the response to immunotherapy. The role of PMRS in the malignant phenotype of hepatocellular carcinoma was explored by conducting a series of in vitro experiments. RESULTS: Our study developed a four-genes PMRS which demonstrates a substantial correlation with the prognosis of HCC patients, serving as an independent predictor in clinical practice. The result of risk-stratified analysis yielded evidence that low-risk patients experienced more favorable clinical outcomes. The nomogram exhibited remarkable prognostic predictive value. The subsequent results revealed that low-risk patients manifested a more promising response to immunotherapy. Moreover, the results of cell experiments demonstrated that the downregulation of DCK markedly inhibited the malignant phenotype of hepatocellular carcinoma. CONCLUSIONS: Our pyrimidine metabolism-centered prognostic signature accurately predicts overall survival, immune status, and treatment response in hepatocellular carcinoma (HCC) patients, offering innovative insights for precise diagnosis, personalized treatment, and improved prognosis.

A comprehensive analysis of the prognostic and immunotherapeutic characteristics of KIFC1 in pan-cancer and its role in the malignant phenotype of pancreatic cancer.

BACKGROUND: Kinesin family member C1 (KIFC1) is an essential member of the motor protein family, which is critically involved in various cellular events, such as mitosis, meiosis, and macromolecular transport, but also in carcinogenesis, malignant progression, and tumor recurrence. METHODS: The analysis determined the relationship between KIFC1 expression, prognosis significance, immune characteristics landscape, and genetic alterations in pan-cancer with the data extracted from web-based platforms and databases, including but not limited to UCSC, NCBI, GEPIA2, HPA, cBioPortal, SangerBox, UALCAN, GEO and TCGA. Additionally, the expression of KIFC1 in pancreatic cancer tumor tissues and adjacent normal tissues was evaluated through immunohistochemistry. In vitro Edu, colony formation, wound healing, and Transwell assay were done to elucidate the biological functions of KIFC1 in pancreatic cancer cells. RESULTS: The analysis revealed that KIFC1 is upregulated in most cancers, and its increased expression is significantly associated with reduced overall survival and disease-free survival in multiple cancer types. Additionally, strong correlations between KIFC1 expression and tumor immunotherapy were observed across various malignancies. Through univariate and multivariate Cox regression analyses using TCGA data, KIFC1 was identified as an independent predictor of prognosis in pancreatic cancer cases. Furthermore, cellular experiments demonstrated that knockdown of KIFC1 resulted in the suppression of cell proliferation, migration, and invasive ability. CONCLUSIONS: Our study indicated that KIFC1 harbors the potential to be a prognostic and immunotherapeutic biomarker of tumors, and it can have an impact on the metastasis and the cell cycle of pancreatic cancer cells.

Adventitial Collagen Cross-Linking by Glutaraldehyde Reinforcing Human Saphenous Vein - Implication for Coronary Artery Bypass Grafting.

INTRODUCTION: A weak venous wall is one of the major reasons contributing to vein graft failure after coronary artery bypass grafting (CABG). We investigated whether adventitial collagen cross-linking by glutaraldehyde reinforces venous wall, preserving the endothelium of veins during high-pressure distention. METHODS: Human saphenous veins (SVs) were collected from 40 patients undergoing CABG, and adventitia cross-linking was performed with 0.3% glutaraldehyde for five minutes. The cross-linked SVs were accessed by biodegradation assay, immunofluorescent staining, and tensile test. Native SVs and cross-linked SVs from another 20 patients received the 200 mmHg pressure distention for two minutes. Pressure-induced injury of SVs were accessed by immunohistochemistry and electron microscopy. RESULTS: Time to digestion was 97±13 minutes for native SVs and 720±0 minutes for cross-linked SVs (P<0.05). After adventitial cross-linking, the collagen I fibres of the vein remarkably presented with compact and nonporous arrangement. In the high-stretch region (stretch ratio 1.4-1.8), the Young's elastic modulus of stress-stretch ratio curve in cross-linked SVs was larger than that in native SVs (13.88 vs. 5.83, P<0.05). The cross-linked SVs had a lower extent of endothelial denudation without fibre fracture during high-pressure distension than native SVs. Comparing with the non-cross-linked SVs, the percentage of endothelial nitric oxide synthase staining length on the endothelium of cross-linked SVs was significantly preserved after high-pressure distension (85.2% vs. 64.7%, P<0.05). CONCLUSION: Adventitial collagen cross-linking by glutaraldehyde reinforced venous wall by increasing stiffness and decreasing extensibility of SVs and mitigated the endothelial damage under high-pressure distension.

Adventitial Collagen Cross-Linking by Glutaraldehyde Reinforcing Human Saphenous Vein - Implication for Coronary Artery Bypass Grafting

ABSTRACT Introduction: A weak venous wall is one of the major reasons contributing to vein graft failure after coronary artery bypass grafting (CABG). We investigated whether adventitial collagen cross-linking by glutaraldehyde reinforces venous wall, preserving the endothelium of veins during high-pressure distention. Methods: Human saphenous veins (SVs) were collected from 40 patients undergoing CABG, and adventitia cross-linking was performed with 0.3% glutaraldehyde for five minutes. The cross-linked SVs were accessed by biodegradation assay, immunofluorescent staining, and tensile test. Native SVs and cross-linked SVs from another 20 patients received the 200 mmHg pressure distention for two minutes. Pressure-induced injury of SVs were accessed by immunohistochemistry and electron microscopy. Results: Time to digestion was 97±13 minutes for native SVs and 720±0 minutes for cross-linked SVs (P<0.05). After adventitial cross-linking, the collagen I fibres of the vein remarkably presented with compact and nonporous arrangement. In the high-stretch region (stretch ratio 1.4-1.8), the Young's elastic modulus of stress-stretch ratio curve in cross-linked SVs was larger than that in native SVs (13.88 vs. 5.83, P<0.05). The cross-linked SVs had a lower extent of endothelial denudation without fibre fracture during high-pressure distension than native SVs. Comparing with the non-cross-linked SVs, the percentage of endothelial nitric oxide synthase staining length on the endothelium of cross-linked SVs was significantly preserved after high-pressure distension (85.2% vs. 64.7%, P<0.05). Conclusion: Adventitial collagen cross-linking by glutaraldehyde reinforced venous wall by increasing stiffness and decreasing extensibility of SVs and mitigated the endothelial damage under high-pressure distension.

The Necessity to Seal the Re-Entry Tears of Aortic Dissection After TEVAR: A Hemodynamic Indicator.

Thoracic endovascular aortic repair (TEVAR) is a common treatment for Stanford type B aortic dissection (TBAD). However, re-entry tears might be found distal to the stented region which transports blood between the true and false lumens. Sealing the re-entry tears, especially for the thoracic tears, could further reduce blood perfusion to the false lumen; however, it might also bring risks by re-intervention or surgery. Wise determination of the necessity to seal the re-entry tears is needed. In this study, patient-specific models of TBAD were reconstructed, and the modified models were established by virtually excluding the thoracic re-entries. Computational hemodynamics was investigated, and the variation of the functional index and first balance position (FBP) of the luminal pressure difference, due to the sealing of the re-entries, was reported. The results showed that the direction of the net flow through the unstented thoracic re-entries varied among cases. Excluding the re-entries with the net flow toward the false lumen may induce the FBP moving distally and the relative particle residence time increasing in the false lumen. This study preliminarily demonstrated that the hemodynamic status of the re-entry tears might serve as an indicator to the necessity of sealing. By quantifying the through-tear flow exchange and shift of FBP, one can predict the hemodynamic benefit by sealing the thoracic re-entries and thus wisely determine the necessity of further interventional management.

Identification of MAD2L1 as a Potential Biomarker in Hepatocellular Carcinoma via Comprehensive Bioinformatics Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is widely acknowledged as a malignant tumor with rapid progression, high recurrence rate, and poor prognosis. At present, there is a paucity of reliable biomarkers at the clinical level to guide the management of HCC and improve patient outcomes. Our research is aimed at assessing the prognostic value of MAD2L1 in HCC. METHODS: Four datasets, GSE121248, GSE101685, GSE85598, and GSE62232, were selected from the GEO database to analyze differentially expressed genes (DEGs) between HCC and normal liver tissues. After functional analysis, we constructed a protein-protein interaction network (PPI) for DEGs and identified core genes in this network with high connectivity with other genes. We assessed the relationship between core genes and the pathogenesis and prognosis of HCC. Finally, we explored the gene regulatory signaling mechanisms involved in HCC pathogenesis. RESULTS: 145 DEGs were screened from the intersection of the four GEO datasets. MAD2L1 was associated with most genes according to the PPI network and was selected as a candidate gene for further study. Survival analysis suggested that high MAD2L1 expression in HCC correlated with a worse prognosis. In addition, real-time quantitative PCR (RT-qPCR), western blot (WB), and immunohistochemistry (IHC) findings suggested that the expression of MAD2L1 was abnormally increased in HCC tissues and cells compared to paraneoplastic tissues and normal hepatocytes. CONCLUSION: We found that high MAD2L1 expression in HCC was significantly associated with overall patient survival and clinical features. We also explored the potential biological properties of this gene.

Multi-stage learning for segmentation of aortic dissections using a prior aortic anatomy simplification.

Aortic dissection (AD) is a life-threatening cardiovascular disease with a high mortality rate. The accurate and generalized 3-D reconstruction of AD from CT-angiography can effectively assist clinical procedures and surgery plans, however, is clinically unavaliable due to the lacking of efficient tools. In this study, we presented a novel multi-stage segmentation framework for type B AD to extract true lumen (TL), false lumen (FL) and all branches (BR) as different classes. Two cascaded neural networks were used to segment the aortic trunk and branches and to separate the dual lumen, respectively. An aortic straightening method was designed based on the prior vascular anatomy of AD, simplifying the curved aortic shape before the second network. The straightening-based method achieved the mean Dice scores of 0.96, 0.95 and 0.89 for TL, FL, and BR on a multi-center dataset involving 120 patients, outperforming the end-to-end multi-class methods and the multi-stage methods without straightening on the dual-lumen segmentation, even using different network architectures. Both the global volumetric features of the aorta and the local characteristics of the primary tear could be better identified and quantified based on the straightening. Comparing to previous deep learning methods dealing with AD segmentations, the proposed framework presented advantages in segmentation accuracy.

Flow analysis of aortic dissection: comparison of inflow boundary conditions for computational models based on 4D PCMRI and Doppler ultrasound.

Computational hemodynamics quantifying the flow environment is an important tool in understanding aortic dissection. In this study, various inflow boundaries were applied on a patient-specific model and compared to the individualized velocimetry. The results indicated that the computations generally overestimated the flow volume and underestimated the wall shear stress. By quantifying the accuracy of the simulation results, two inflow settings were suggested. One was individualized, the PCMRI-extracted 4D flow information, and the other was averaged by healthy data, the ultrasound-extracted averaged flow waveform with parabolic velocity profile. This study might contribute to improving the precise computation of aortic dissection hemodynamics.

3D Morphologic Findings Before and After Thoracic Endovascular Aortic Repair for Type B Aortic Dissection.

BACKGROUND: Stanford type-B aortic dissection (TBAD) is commonly treated by thoracic endovascular aortic repair (TEVAR). Usually, the implanted stent-grafts will not cover the entire dissection-affected region for those patients with dissection extending beyond the thoracic aorta, thus the fate of the uncovered aortic segment is uncertain. This study used 3-dimensional measurement of aortic morphological changes to classify the different remodeling effects of TBAD patients after TEVAR, and hypothesized that not only initial morphological features, but also their change over time at follow-up are associated with the remodeling. METHODS: Forty-one TBAD patients underwent TEVAR and CT-angiography before and after the intervention (twice or more follow-ups) were included in this study. According to the false-lumen volume variations post-TEVAR, patients who had abdominal aortic expansion at the second follow-up were classified into the Enlarged (n =12, 29%) and remaining into the Stable group (n = 29, 71%). 3D morphological parameters were extracted on precise reconstruction of imaging datasets. Statistical differences in 3D morphological parameters over time between the 2 groups and the relationship among these parameters were analyzed. RESULTS: In the Enlarged group, the number of all tears before TEVAR was significantly higher (P = 0.022), and the size of all tears at the first and second follow-up post-TEVAR were significantly higher than that in the Stable group (P = 0.008 and P = 0.007). The location of the primary tear was significantly higher (P = 0.031) in the Stable group. The cross-sectional analysis of several slices below the primary tear before TEVAR shows different shape features of the false lumen in the Stable (cone-like) and Enlarged (hourglass-like) groups. The number of tears before TEVAR has a positive correlation with the post-TEVAR development of dissection (r = 0.683, P = 0.00). CONCLUSION: The results in this study indicated that the TBAD patients with larger tear areas, more re-entry tears and with the primary tear proximal to the arch would face a higher risk of negative remodeling after TEVAR.

Computed tomography-based hemodynamic index for aortic dissection.

OBJECTIVE: In this study we aimed to propose a new computed tomography-based hemodynamic indicator to quantify the functional significance of aortic dissection and predict post intervention luminal remodeling. METHODS: Computational hemodynamics and 3D structural analyses were conducted in 51 patients with type B aortic dissection, at initial presentation and at approximately 1 month, 3 months, and 1 year post intervention. A functional index was proposed on the basis of luminal pressure difference. Statistical relationships between the proposed indicator and longitudinal luminal development were analyzed. RESULTS: The computed luminal pressure difference (true lumen pressure minus false lumen pressure) varied overall from positive to negative along the aorta. The first balance position at which the pressure difference equals 0 was proposed as the functional indicator. A more distally located first balance position indicated better functional status. Implantation of stent graft distally shifted this balance position. Patients with the balance position shifted out of the dissected region (43%) presented the highest functional improvement after intervention; whereas those with the balance position shifted to the abdominal region (25%) showed unsatisfactory results. The magnitude of distal shifting of the first balance position at 3 months post intervention was statistically related to the subsequent true lumen expansion and false lumen reduction. CONCLUSIONS: The first balance position of luminal pressure difference quantified the hemodynamic status of the dissected aorta. The magnitude of distal shifting of the balance position after intervention was associated with functional improvement and might be used predict longitudinal aortic remodeling.

Retrograde branched extension limb assembling stent of pararenal abdominal aortic aneurysm: A longitudinal hemodynamic analysis for stent graft migration.

PURPOSE: Pararenal abdominal aortic aneurysms (PRAAAs) are a life-threatening disease, and hemodynamic analysis may provide greater insight into the effectiveness and long-term outcomes of endovascular aneurysm repair (EVAR). However, the lack of patient-specific boundary conditions on the periphery compromises the accuracy. Windkessel (WK) boundary conditions coupled to hemodynamic follow-up models of a PRAAA patient, aims to provide insights into the link between hemodynamics and poor prognosis. METHOD: One PRAAA patient underwent EVAR and reintervention after one branch of stent-graft (SG) had migrated. Totally five computational follow-up models were studied. Patient-specific flow data acquired via ultrasound were used to define the boundary conditions in the ascending aorta and the following three branches. Coupled zero-dimensional WK models representing the distal vasculature were used to define the outlet boundary conditions under the abdomen. RESULTS: Flow divisions of the main SG branches were 40.7% and 24.7%, respectively. Time-averaged wall shear stress and oscillatory shear index (OSI) increased at the junction connected the SG branch and the stent leading to the right common iliac artery (RCIA) where the stent migrated. The OSI and relative residence time (RRT) value in superior mesenteric artery increased notably after the migration, the RRT continuously increased following the reintervention. CONCLUSION: Unbalanced flow, resulting in locally high-speed flow, high WSS and OSI might significantly affect stent stability. Results suggest that diameters and interconnection design of stents in complex cases should take the flow division into consideration and computational simulations might be considered as a tool for intervention protocol design.

Optimization schemes for endovascular repair with parallel technique based on hemodynamic analyses.

Endovascular repair with parallel stent-grafts (SG) is a challenging technique that reconstructs the luminal flow pathways by implanting parallel-placed SGs into the vessel. After treatment, occlusion and shifting of the parallel SGs are sometimes reported, which could be fatal and difficult to be re-operated. These issues are highly related to the local hemodynamic conditions in the stented region. In this study, a patient case treated by the octopus endograft technique (a head-SG with three limb-SGs) and experienced limb-SG occlusion is studied. 3-D models are established based on computed tomography (CT) angiography datasets pretreatment and posttreatment as well as during follow-ups. Hemodynamic quantities such as pressure drop, wall shear stress-related parameters, and flow division in limb-SGs and visceral arteries are quantitatively investigated. Optimizations on the length of the head-SG and diameter of the limb-SGs are analyzed based on various scenarios. The results indicate that when reconstructing the flow pathways via octopus stenting, it is important to ensure the flow distribution as physiologically required with this new morphology. Position (or length) of the head-SG and diameter of the limb-SGs play an important role in controlling flow division, and high time average wall shear stress (TAWSS) around the head-SG acts as a main factor for graft immigration. This study, by proposing optimization suggestions with hemodynamic analyses for a specific case, implicates that pretreatment SG scenarios may assist in wise selection and placement of the device and thus may improve long-term effectiveness of this kind of challenging endovascular repair techniques.

Virtual stenting with simplex mesh and mechanical contact analysis for real-time planning of thoracic endovascular aortic repair.

In aortic endovascular repair, the prediction of stented vessel remodeling informs treatment plans and risk evaluation; however, there are no highly accurate and efficient methods to quantitatively simulate stented vessels. This study developed a fast virtual stenting algorithm to simulate stent-induced aortic remodeling to assist in real-time thoracic endovascular aortic repair planning. Methods: The virtual stenting algorithm was established based on simplex deformable mesh and mechanical contact analysis. The key parameters of the mechanical contact analysis were derived from mechanical tests on aortic tissue (n=40) and commonly used stent-grafts (n=6). Genetic algorithm was applied to select weighting parameters. Testing and validation of the algorithm were performed using pre- and post-treatment computed tomography angiography datasets of type-B aortic dissection cases (n=66). Results: The algorithm was efficient in simulating stent-induced aortic deformation (mean computing time on a single processor: 13.78±2.80s) and accurate at the morphological (curvature difference: 1.57±0.57%; cross-sectional area difference: 4.11±0.85%) and hemodynamic (similarity of wall shear stress-derived parameters: 90.16-90.94%) levels. Stent-induced wall deformation was higher (p<0.05) in distal stent-induced new entry cases than in successfully treated cases, and this deformation did not differ significantly among the different stent groups. Additionally, the high stent-induced wall deformation regions and the new-entry sites overlapped, indicating the usefulness of wall deformation to evaluate the risks of device-induced complications. Conclusion: The novel algorithm provided fast real-time and accurate predictions of stent-graft deployment with luminal deformation tracking, thereby potentially informing individualized stenting planning and improving endovascular aortic repair outcomes. Large, multicenter studies are warranted to extend the algorithm validation and determine stress-induced wall deformation cutoff values for the risk stratification of particular complications.

The Motion of An Inv Nodal Cilium: a Realistic Model Revealing Dynein-Driven Ciliary Motion with Microtubule Mislocalization.

BACKGROUND/AIMS: Nodal cilia that rotate in the ventral node play an important role in establishing left-right asymmetry during embryogenesis; however, inv mutant cilia present abnormal movement and induce laterality defects. The mechanism of their motility, which is regulated by dynein activation and microtubule arrangement, has not been fully understood. This study analyzed the dynein-triggered ciliary motion in the abnormal ultrastructure of the inv mutant, aiming to quantitatively evaluate the influence of microtubule mislocalization on the movement of the cilium. METHODS: We established a realistic 3-D model of an inv mutant cilium with an ultrastructure based on tomographic datasets generated by ultra-high voltage electron microscopy. The time-variant activation of the axonemal dynein force was simulated by pairs of point loads and embedded at dynein-mounted positions between adjacent microtubule doublets in this mathematical model. Utilizing the finite element method and deformable grid, the motility of the mutant cilium that is induced by various dynein activation hypotheses was investigated and compared to experimental observation. RESULTS: The results indicate that for the inv mutant, simulations of the ciliary movement with the engagement of dyneins based on the distance-controlled pattern in the partially activation scenario are broadly consistent with the observation; the shortening of the microtubules induces smaller movement amplitudes, while the angles of the mislocalized microtubules affect the pattern of the ciliary movement, and during the ciliary movement, the microtubules swing and twist in the mutant ciliary body. CONCLUSION: More generally, this study implies that dynein engagement is sensitive to subtle geometric changes in the axoneme, and thus, this geometry greatly influences the integrity of a well-formed ciliary rotation.

Hemodynamic parameters that may predict false-lumen growth in type-B aortic dissection after endovascular repair: A preliminary study on long-term multiple follow-ups.

Thoracic endovascular aortic repair (TEVAR) is commonly applied in type-B aortic dissection. For patients with dissection affects descending aorta and extends downward to involve abdominal aorta and possibly iliac arteries, false lumen (FL) expansion might occur post-TEVAR. Predictions of dissection development may assist in medical decision on re-intervention or surgery. In this study, two patients are selected with similar morphological features at initial presentation but with different long-term FL development post-TEVAR (stable and enlarged FL). Patient-specific models are established for each of the follow-ups. Flow boundaries and computational validations are obtained from Doppler ultrasound velocimetry. By analyzing the hemodynamic parameters, the false-to-true luminal pressure difference (PDiff) and particle relative residence time (RRT) are found related to FL remodeling. It is found that (i) the position of the first FL flow entry is the watershed of negative-and-positive PDiff and, in long-term follow-ups, and the position of largest PDiff is consistent with that of the greatest increase of FL width; (ii) high RRT occurs at the FL proximal tip and similar magnitude of RRT is found in both stable and enlarged cases; (iii) comparing to the RRT at 7days post-TEVAR, an increase of RRT afterwards in short-term is found in the stable case while a slight decrease of this parameter is found in the enlarged case, indicating that the variation of RRT in short-term post-TEVAR might be potential to predict long-term FL remodeling.

The Significance of the Angle between Superior Mesenteric Artery and Aorta in Spontaneous Isolated Superior Mesenteric Artery Dissection.

BACKGROUND: The aim of this study is to assess the significance of the angle between superior mesenteric artery (SMA) and distal aorta in spontaneous isolated superior mesenteric artery dissection (SISMAD) by clinical and biomechanical analyses. METHODS: Thirty-seven patients with SISMAD (1 asymptomatic) and 148 controls (1:4 matched for age [mean 50.2 years], gender [92% male], and body mass index, and being ruled out for arterial disease) underwent aortic computed tomography angiography. SMA-distal aorta angle, measured on sagittal plane, was compared along with baseline characteristics (body mass index, smoking history, and comorbidities) between groups, and assessed as tool to evaluate SISMAD risk after stratification into 4 angle-interval categories. Flow analysis and fluid-structure interaction study were conducted based on patient-specific models with ultrasound-measured boundary conditions to further reveal the flow pattern and loading distribution in the 4 angle-interval categories. RESULTS: SISMAD patients versus controls had larger mean SMA-distal aorta angle (73 ± 19.8° vs. 50 ± 18.81°, P < 0.001), and more frequently smoking history (62% vs. 40%, P = 0.02) and hypertension (59% vs. 34%, P < 0.001), all multivariate predictors of no SISMAD (odds ratio 0.946 [95% confidence interval 0.927-0.966]; 0.415 [0.198-0.87]; and 0.252 [0.117-0.544], respectively). Odds ratio for SISMAD increased with increasing SMA-distal aorta angle (1, 10, 57, and 73 for <50°, 50-69°, 70-90°, and >90°, respectively; P < 0.05 for >70°). In silico study confirmed that larger angle is associated with higher stress in the arterial wall and higher oscillatory shear index in the vessel lumen at the SMA superior convex, where dissection commonly occurs. CONCLUSIONS: Besides smoking history and hypertension, SISMAD was positively associated with a morphological parameter, the SMA-distal aorta angle. This might be due to the greater wall stress and oscillatory stress index in the arterial convex with a larger angle.

Successful use of retrograde branched extension limb assembling technique in endovascular repair of pararenal abdominal aortic aneurysm.

Surgeon-modified retrograde branched extension limb assembling technique and bridged endografts were successfully used to exclude an asymptomatic pararenal abdominal aortic aneurysm and to reconstruct the superior mesenteric artery and bilateral renal arteries in a case with high-grade celiac artery stenosis, nondilated aorta above the superior mesenteric artery, and large lumen below the renal arteries. In patient-specific models for hemodynamics analysis, enhanced flow diversion to visceral arteries up to 6-month follow-up confirmed treatment feasibility; however, endograft configurations could be improved to avoid sharp corners at bifurcations, thereby ensuring smooth flow transport and possibly reducing risk for endograft narrowing or the development of thrombosis.

[Analysis of the Physiological Activities and Functions in Vitro of Apheresis Platelets during Storage].

OBJECTIVE: To investigate the changes of physiological activities and functions in vitro of apheresis platelets during storage. METHOD: 17 units of apheresis platelets were randomly chosen and stored at 20 °C to 24 °C with agitation. Platelet counting (Plt), mean platelet volume (MPV), blood gases, pH value, glucose (Glu) concentration, lactate (LA) concentration, LDH concentration, thromboelastogram (TEG), hypotonic shock response (HSR), CD62p expression rate and anew expression rate were measured on days 0, 1, 3, 5 after platelet storage. Changes of physiological activities and functions in vitro were systematically evaluated by above-mentioned indexes. RESULTS: During storage, Plt, MPV and HSR were not significantly changed; but pH value, blood gases, Glu, LA, LDH, HSR, expression rate of CD62p and anew expression rate were significant differenty. Among thromboelastogram indexes, R value increased obviously with prolongation of storage time; K value and αAngle were not significantly changed; MA was not significantly changed on day 1 and 3, but was slightly increase on day 5. CONCLUSION: The physiological activities and functions in vitro of apheresis platelets are kept well during storage. For clinical transfusion of apheresis platelet during storage, clinical effect of transfusione is not influenced.

[Analysis of Patients' Irregular Antibody Screening and Identification Results before Blood Transfusion].

OBJECTIVE: To analyze the results of irregular antibody screening and identification among patients before blood transfusion, and to investigate the specific distribution of irregular antibodies and the distribution regularity in different diseases. METHODS: Choosing the patients intended to be transfused in our hospital from January 1, 2009 to December 31, 2013 years, micro-column gel technique was used to screen the irregular antibodies of those receptors and to identify the antibody specificity of the positive specimens. RESULTS: Among 44194 patients, 137 patients were with irregular antibody positive and their positive rate was 0.31%, among them 33 cases were male and accounted for 0.18% in the studied males; the 104 cases were females and accounted for 0.40% in all the studied females. The difference of sex distribution was statistically significant (X2=15.38, P<0.05). In the irregular antibody screening positive patients, patients with transfusion or pregnancy history were 129 cases, and the patients without transfusion or pregnancy history were 8 cases. In the irregular antibody screening positive patients, the main antibody of 54 cases belongs to Rh blood type system, accounting for 39.42%; The main antibody of 37 cases belongs to MNS blood type system, accounting for 27.01%; while the 30 cases belong to Lewis blood type system, accounting for 21.90%. According to the classification of diseases, the irregular antibody screening-positive patients with tumors were ranked in the highest rate at 5.96‰, the secondary hemorrhage of digestive tract and chronic renal failure were ranked at the rate of 3.28‰ and 3.19‰. The difference of positive rates between diseases was statistically significant (χ2=19.33, P<0.05). CONCLUSION: Irregular antibody screening before blood transfusion is necessary, which can discover the irregular antibodies of clinical significance, especially for patients with tumors and the other patients with the history of frequent blood transfusions or multiple pregnancies. Antibody screening is a useful warning signal, as it ensures the safety of blood transfusions.

Nestin positively regulates the Wnt/ß-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells.

INTRODUCTION: We investigated Nestin expression in triple-negative breast cancer and examined how the modulation of Nestin expression affects cell cycle progression, survival, invasion and regulatory signaling in breast cancer stem cells (CSC) in vitro. METHODS: Nestin expression in 150 triple-negative breast cancer specimens were examined by immunohistochemistry. The role of Nestin expression in tumorigenesis was examined by assaying naturally occurring Nestinhigh/Nestinlow CSC from 12 breast cancer tissues, as well as CSC from 26 clinical specimens, where Nestin overexpression and silencing was achieved by genetic manipulation, for their ability to form mammospheres and induce solid tumors. Cell cycle progression, spontaneous apoptosis and invasiveness of Nestin-silenced breast CSC were investigated by flow cytometry and transwell assays. The relative levels of expression of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathway-related molecules were determined by western blotting. RESULTS: Nestin expression was significantly associated with poor survival in patients with triple-negative breast cancer (P = 0.01). Nestinhigh breast CSC rapidly formed typical mammospheres in vitro. Nestinhigh, but not Nestinlow CSC, efficiently formed solid tumors in vivo. Nestin silencing induced cell cycle arrest at G2/M (52.03% versus 19.99% in controls) and promoted apoptosis (36.45% versus 8.29% in controls). Nestin silencing also inhibited breast CSC invasiveness, and was associated with significantly upregulated E-cadherin, while N-cadherin, vimentin, a-smooth muscle actin (a-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression was downregulated (P <0.05 for all). Nestin silencing also upregulated Axin, glycogen synthase kinase-3 beta (GSK-3ß), adenomatous polyposis coli (APC), and peroxisome proliferator-activated receptor alpha (PPARa), and downregulated ß-catenin, c-Myc, cyclin D and MMP-7 expression in CSC. Inhibition of the Wnt/ß-catenin pathway mitigated mammosphere formation in Nestinhigh CSC, while inhibition of GSK-3ß promoted the mammosphere formation in Nestinlow CSC (P <0.05 for all). CONCLUSIONS: Our data indicates that Nestin positively regulates the proliferation, survival and invasiveness of breast CSC by enhancing Wnt/ß-catenin activation.