Classification and prediction of chemoradiotherapy response and survival from esophageal carcinoma histopathology images.

Whole slide imaging (WSI) of Hematoxylin and Eosin-stained biopsy specimens has been used to predict chemoradiotherapy (CRT) response and overall survival (OS) of esophageal squamous cell carcinoma (ESCC) patients. This retrospective study collected 279 specimens in 89 non-surgical ESCC patients through endoscopic biopsy between January 2010 and January 2019. These patients were divided into a CRT response group (CR + PR group) and a CRT non-response group (SD + PD group). The WSIs have segmented approximately 1,206,000 non-overlapping patches. Two experienced pathologists manually delineated the eight types of tissues on 32 WSIs, including esophagus tumor cell (TUM), cancer-associated stroma (CAS), normal epithelium layer (NEL), smooth muscle (MUS), lymphocytes (LYM), Red cells (RED), debris (DEB), uneven areas (UNE). The chemoradiotherapy response prediction models were built using maximum relevance-minimum redundancy (MRMR) feature selection and least absolute shrinkage and selection operator (LASSO) regression. However, pathological features with p < 0.1 were selected and integrated to be further screened using a LASSO Cox regression model to build a multivariate Cox proportional hazards model for predicting the OS. The testing accuracy of the tissue classification model was 91.3 %. The pathological model created using two CAS in-depth features and eight TUM in-depth features performed best for the prediction of treatment response and achieved an AUC of 0.744. For the prediction of OS, the testing AUC of this model at one year and three years were 0.675 and 0.870, respectively. The TUM model showed the highest AUC at one year (0.712). With its high accuracy rate, the deep learning model has the potential to transform from bench to bedside in clinical practice, improve patient's quality of life, and prolong the OS rate.

Emergency exploratory laparotomy and radical gastrectomy in patients with gastric cancer combined with acute upper gastrointestinal bleeding.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor worldwide and ranks as the fourth leading cause of cancer-related mortality. Upper gastrointestinal bleeding (UGIB) is a frequent complication of GC. Radical gastrectomy and palliative therapy are widely used surgical procedures in the clinical management of GC. This study intends to probe the clinical efficacy and safety of radical gastrectomy and palliative therapy on the basis of exploratory laparotomy in patients with GC combined with UGIB, hoping to provide valuable information to aid patients in selecting the appropriate surgical intervention. AIM: To investigate the clinical efficacy and safety of exploratory laparotomy + radical gastrectomy and palliative therapy in patients with GC and UGIB combined. METHODS: A total of 89 GC patients admitted to the First Affiliated Hospital of the University of South China between July 2018 and July 2020 were selected as participants for this study. The 89 patients were divided into two groups: radical resection group (n = 46) treated with exploratory laparotomy + radical gastrectomy and Palliative group (n = 43) treated with palliative therapy. The study compared several variables between the two groups, including surgical duration, intraoperative blood transfusion volume, postoperative anal exhaust time, off-bed activity time, length of hospitalization, and incidence of complications such as duodenal stump rupture, anastomotic obstruction, and postoperative incision. Additionally, postoperative immune function indicators (including CD3+, CD4+, CD8+, CD4+/CD8+, and CD3+/HLADR+), immunoglobulin (IgG and IgM), tumor markers (CEA, CA199, and CA125), and inflammatory factors (IL-6, IL-17, and TNF-α) were assessed. The surgical efficacy and postoperative quality of life recovery were also evaluated. The patients were monitored for survival and tumor recurrence at 6 mo, 1 year, and 2 years post-surgery. RESULTS: The results indicated that the duration of operation time and postoperative hospitalization did not differ between the two surgical procedures. However, patients in the radical resection group exhibited shorter intraoperative blood loss, anus exhaust time, off-bed activity time, and inpatient activity time than those in the Palliative group. Although there was no substantial difference in the occurrence of postoperative complications, such as duodenal stump rupture and anastomotic obstruction, between the radical resection group and Palliative group (P > 0.05), the radical resection group exhibited higher postoperative immune function indicators (including CD3+, CD4+, CD8+, etc.) and immunoglobulin levels (IgG, IgM) than the Palliative group, while tumor markers and inflammatory factors levels were lower than those in the radical resection group. Additionally, surgical efficacy, postoperative quality of life, and postoperative survival rates were higher in patients who underwent radical gastrectomy than in those who underwent palliative therapy. Moreover, the probability of postoperative tumor recurrence was lower in the radical gastrectomy group compared to the palliative therapy group, and these differences were all statistically significant (P < 0.05). CONCLUSION: Compared to palliative therapy, exploratory laparotomy + radical gastrectomy can improve immune function, reduce the levels of tumor markers and inflammatory factors, improve surgical efficacy, promote postoperative quality of life recovery, enhance survival rates, and attenuate the probability of tumor recurrence.

Circ_0001714 knockdown alleviates lipopolysaccharide-induced apoptosis and inflammation in renal tubular epithelial cells via miR-129-5p/TRAF6 axis in septic acute kidney injury.

BACKGROUND: Circular RNAs (circRNAs) have been shown to play roles in regulating sepsis. Sepsis is a major cause of acute kidney injury (AKI). Herein, we aimed to investigate the role and mechanism of circ_0001714 in the progression of sepsis-induced AKI. METHODS: Human HK-2 cells were exposed to lipopolysaccharide (LPS) for functional experiments. Quantitative real-time polymerase chain reaction and western blotting were used for expression analysis. Functional experiments were performed by using MTT assay, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). The binding between miR-129-5p and circ_0001714 or TRAF6 (TNF receptor associated factor 6) was validated using dual-luciferase reporter assay. RESULTS: Circ_0001714 expression was higher in sepsis-AKI patients. HK-2 cells were exposed to LPS to imitate the injury of renal tubular epithelial cells during sepsis-AKI. LPS dose-dependently up-regulated circ_0001714, moreover, circ_0001714 silencing reversed LPS-evoked apoptosis and inflammation in HK-2 cells. Mechanistically, circ_0001714 sequestered miR-129-5p to up-regulate TRAF6 expression, implying the circ_0001714/miR-129-5p/TRAF6 feedback loop. MiR-129-5p was decreased, while TRAF6 was increased in sepsis-AKI patients and LPS-stimulated HK-2 cells. MiR-129-5p re-expression or TRAF6 silencing protected against LPS-induced HK-2 cell apoptosis and inflammation. Additionally, a series of rescue experiments showed that miR-129-5p inhibition reversed the inhibitory action of circ_0001714 knockdown on LPS-induced HK-2 cell injury. Furthermore, TRAF6 overexpression also attenuated the protective effects of miR-129-5p on HK-2 cells under LPS treatment. CONCLUSION: Circ_0001714 silencing might alleviate LPS-induced apoptosis and inflammation via targeting miR-129-5p/TRAF6 axis in HK-2 cells.

CIRC_0001818 TARGETS MIR-136-5P TO INCREASE LIPOPOLYSACCHARIDE-INDUCED HK2 CELL INJURIES BY ACTIVATING TXNIP/NLRP3 INFLAMMASOME PATHWAY.

ABSTRACT: Background: The implication of circular RNAs (circRNAs) in sepsis-related complications arouses much attention, which provides additional treatment options for sepsis-related complications. The purpose of this study is to unveil the function and functional mechanism of circ_0001818 in cell models of septic acute kidney injury (AKI). Methods: Septic AKI cell models were constructed using HK2 cells treated with lipopolysaccharide (LPS). The expression levels of circ_0001818, miR-136-5p, and thioredoxin interacting protein (TXNIP) mRNA were examined by quantitative real-time polymerase chain reaction. Cell viability and death were explored by CCK-8 and flow cytometry assays. The activity of oxidative stress-related markers was examined using commercial kits. The secretion of inflammatory factors was examined using ELISA kits. The binding between miR-136-5p and circ_0001818 or TXNIP was validated by dual-luciferase reporter test and pull-down assay. The receiver operating characteristic curve was depicted to assess the diagnostic value of circ_0001818, miR-136-5p, and TXNIP in serumal exosomes from patients with septic AKI. Results: Circ_0001818 expression was elevated in LPS-treated HK2 cells. Loss-of-function assays displayed that circ_0001818 downregulation alleviated LPS-induced HK2 cell death, oxidative stress, inflammatory release, and inflammasome activation. MiR-136-5p was targeted by circ_0001818, and inhibition of miR-136-5p attenuated the effects of circ_0001818 downregulation, thus recovering LPS-induced HK2 cell injuries. MiR-136-5p targeted the downstream TXNIP, and circ_0001818 dysregulation could affect TXNIP expression via targeting miR-136-5p. Overexpression of TXNIP overturned the effects of circ_0001818 downregulation. Moreover, circ_0001818, miR-136-5p, and TXNIP in serumal exosomes had diagnostic values. Conclusions: Circ_0001818 targets miR-136-5p to activate TXNIP expression, leading to the contribution of LPS-induced HK2 cell injury.

CIRC_0008882 STIMULATES PDE7A TO SUPPRESS SEPTIC ACUTE KIDNEY INJURY PROGRESSION BY SPONGING MIR-155-5P.

ABSTRACT: Background: The importance of circular RNA (circRNA) in the progression of septic acute kidney injury (AKI) was gradually recognized. It has been confirmed that circ_0008882 expression was decreased in the blood of patients with AKI. However, the role of circ_0008882 in septic AKI progression remains unclear. Methods: Human kidney-2 (HK2) cells were stimulated with lipopolysaccharide (LPS) to establish a septic AKI cell model. The RNA and protein expression of circ_0008882, miR-155-5p, phosphodiesterase 7A (PDE7A), PCNA, Bax, and Bcl-2 were detected by quantitative real-time polymerase chain reaction and Western blot. Cell viability was investigated by cell counting kit-8 assay. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the levels of inflammatory factors (TNF-α, IL-1ß, and IL-6). Flow cytometry was implemented to evaluate cell cycle and cell apoptosis. The Caspase3 activity was examined using Caspase3 Assay Kit. Dual-luciferase reporter assay and RNA immunoprecipitation assay were applied to verify the molecular target relations. Results: Septic AKI serum samples and LPS-induced HK2 cells displayed low expression of circ_0008882 and PDE7A, and high expression of miR-155-5p when compared with the controls. Overexpression of circ_0008882 relieved LPS-induced HK2 cell injury. MiR-155-5p was a target of circ_0008882, and miR-155-5p mimic restored circ_0008882 overexpression-mediated effects on LPS-treated HK2 cells. PDE7A was identified as a target gene of miR-155-5p, and PDE7A downregulation almost reverted the improvement impacts induced by the miR-155-5p inhibitor. Conclusions: Overexpression of circ_0008882 impeded LPS-induced HK2 cell injury by modulating miR-155-5p/PDE7A pathway, implying that circ_0008882 might be a possible circRNA-targeted therapy for septic AKI.

Molecular mechanism of Acanthopanax senticosus in the treatment of Alzheimer's disease based on network pharmacology and molecular docking.

Alzheimer's disease is the most common neurodegenerative disease. Acanthopanax senticosus, also known as Ciwujia or Siberian ginseng in Chinese, has a wide range of antioxidant and anti-inflammatory activities. The study aims to explore the action mechanism of A. senticosus against Alzheimer's disease using network pharmacology and molecular docking. The active ingredients and targets of A. senticosus were searched through the ETCM database, and Alzheimer's disease-related targets were obtained through the OMIM and GeneCards databases. The Cytoscape 3.7.2 software was used to construct a "drug-component-target" relationship network, and the target genes of A. senticosus against Alzheimer's disease were imported into the String database to establish a protein interaction (PPI) network. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes gene enrichment analyses were performed through the Metascape database to obtain potential pathways of action of A. senticosus for the treatment of Alzheimer's disease, and the ability of these active ingredients to bind to core targets was then verified by molecular docking. 51 active ingredients were screened from A. senticosus, and 88 effective targets for Alzheimer's disease were screened. Topological and pathway-enrichment analyses revealed that A. senticosus could play a beneficial role in the treatment of Alzheimer's disease by regulating apoptosis and inflammation. Molecular docking results showed that Ciwujianoside B, Chiisanoside, and Ciwujianoside D1 had strong binding abilities to key target proteins (TNFα, IL1ß, and CASP3). Collectively, A. senticosus is feasible in the treatment of Alzheimer's disease.

Bifocal flat lens with different imaging characteristics for a dual-sensor imaging system.

Wide field of view (FOV) images and magnified images can be taken simultaneously by dual-sensor imaging systems. Here, we propose an approach for creating a bifocal flat lens with different imaging characteristics of its two foci, which makes dual-sensor imaging systems more integrated and miniaturized. That is, two special parts of two different conventional ZP are extracted and then combine the two elements in a specific way. So that there are two foci with different characteristics along the optical axis, one is long focus with higher resolution, the other is short focus with long depth of focus (DOF). Under the proposed approach, a thin and light bifocal diffractive lens (BDL) with thickness of 0.6 µm is developed. The long and short focal lengths of the BDL are ~ 81 mm and ~ 27 mm, respectively, with a diameter of 6 mm. We experimentally demonstrate that the long focus of the BDL is capable of taking high-resolution magnified images, and its resolution is up to 21.90″. The short focus is able to take wide FOV with long DOF images, and two objects spread 2880 mm apart can be imaged clearly. The experiment results demonstrate that all of these metrics are better than those of a conventional refractive lens.

Extended the depth of field and zoom microscope with varifocal lens.

Extending the depth of field (DOF) is especially essential in thick and 3D sample imaging. However, it's difficult to achieve both large DOF and high resolution in a zoom microscope. Currently, the use of optical sectioning to expand DOF still has the problem of inconstant magnification. Here, we develop an extended the depth of field (EDOF) and zoom microscope, which can realize EDOF with constant magnification and high resolution. Besides, the proposed microscope can achieve optical axial scanning at different NA and magnifications in real time without any mechanical movement. The proposed varifocal lens is employed to realize optical axial scanning, zooming, and keeping constant magnification when extending the DOF. Experimental results show that the proposed microscope can realize a continuous optical zoom of 10-40×, NA from 0.14 to 0.54, and the DOF of microscope can be extended to 1.2 mm.

Cross-subject EEG emotion recognition combined with connectivity features and meta-transfer learning.

In recent years, with the rapid development of machine learning, automatic emotion recognition based on electroencephalogram (EEG) signals has received increasing attention. However, owing to the great variance of EEG signals sampled from different subjects, EEG-based emotion recognition experiences the individual difference problem across subjects, which significantly hinders recognition performance. In this study, we presented a method for EEG-based emotion recognition using a combination of a multi-scale residual network (MSRN) and meta-transfer learning (MTL) strategy. The MSRN was used to represent connectivity features of EEG signals in a multi-scale manner, which utilized different receptive fields of convolution neural networks to capture the interactions of different brain regions. The MTL strategy fully used the merits of meta-learning and transfer learning to significantly reduce the gap in individual differences between various subjects. The proposed method can not only further explore the relationship between connectivity features and emotional states but also alleviate the problem of individual differences across subjects. The average cross-subject accuracies of the proposed method were 71.29% and 71.92% for the valence and arousal tasks on the DEAP dataset, respectively. It achieved an accuracy of 87.05% for the binary classification task on the SEED dataset. The results show that the framework has a positive effect on the cross-subject EEG emotion recognition task.

Relaxation Degree Analysis Using Frontal Electroencephalogram Under Virtual Reality Relaxation Scenes.

Increasing social pressure enhances the psychological burden on individuals, and the severity of depression can no longer be ignored. The characteristics of high immersion and interactivity enhance virtual reality (VR) application in psychological therapy. Many studies have verified the effectiveness of VR relaxation therapy, although a few have performed a quantitative study on relaxation state (R-state). To confirm the effectiveness of VR relaxation and quantitatively assess relaxation, this study confirmed the effectiveness of the VR sightseeing relaxation scenes using subjective emotion scale and objective electroencephalogram (EEG) data from college students. Moreover, some EEG features with significant consistent differences after they watched the VR scenes were detected including the energy ratio of the alpha wave, gamma wave, and differential asymmetry. An R-state regression model was then built using the model stacking method for optimization, of which random forest regression, AdaBoost, gradient boosting (GB), and light GB were adopted as the first level, while linear regression and support vector machine were applied at the second level. The leave-one-subject-out method for cross-validation was used to evaluate the results, where the mean accuracy of the framework achieved 81.46%. The significantly changed features and the R-state model with over 80% accuracy have laid a foundation for further research on relaxation interaction systems. Moreover, the VR relaxation therapy was applied to the clinical treatment of patients with depression and achieved preliminary good results, which might provide a possible method for non-drug treatment of patients with depression.

Zoom liquid lens employing a multifocal Fresnel zone plate.

We propose a zoom liquid lens employing a multifocal Fresnel zone plate. The proposed lens has two optical surfaces: liquid-liquid interface and Fresnel zone plate. The Fresnel zone plate is designed to have a multifocal point and an increased depth of focus. Therefore, the proposed lens has two obvious advantages. Due to increased depth of focus, the proposed lens can realize zooming using only one tunable liquid-liquid interface, which is not available for conventional liquid lens. Thus, it is possible to remove conventional zooming mechanisms from cameras. Besides, the focal length tuning range is also increased, and a lens system based on the proposed lens can simultaneously collect two images with different magnifications. We present the design, fabrication and characterization of the proposed lens. The shortest positive and negative focal length are ∼17.5mm and ∼-34.5mm and the diameter is 5mm. The zoom ratio of the proposed lens reaches ∼1.48×. Our results confirm that the proposed lens has widespread applications in imaging system.

Outcomes of uncomplicated Type B intramural hematoma patients with Type 2 diabetes mellitus.

OBJECTIVES: We aimed to summarize the clinical presentations, therapeutic approaches, and outcomes of Type B intramural hematoma (IMHB) patients with and without Type 2 diabetes mellitus (DM). METHODS: Patients with uncomplicated IMHBs were included between January 2016 and January 2018 and divided into two groups according to whether or not they had DM. We also assessed the potential diagnostic value of serum matrix metalloproteinase-9 (MMP-9) level and the association of it with the disease progression of uncomplicated IMHB patients with and without DM. RESULTS: A total of 149 patients were included (DM group [n = 60] and non-DM group [n = 89]). Patients in the non-DM group underwent thoracic endovascular aortic repair treatment more frequently (12% vs 2%, p = .028) and had a higher reintervention rate during the follow-up (9 in 81 patients, 11% vs. 2%, p = .043). There were significant differences between the two groups regarding the aorta-related mortality rate during the acute phase (9% vs. 0%, p = .042) and the all-cause mortality rate (22% vs. 7%, p = .011). Ulcer-like projection (ULP) development (during the acute phase; hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.15-1.79, p = .005), C-reactive protein (CRP) levels (HR, 2.08; 95% CI, 1.91-3.91, p = .003), and MMP-9 levels (HR, 15.77; 95% CI, 6.48-21.62, p < .001) were associated with an elevated risk for aorta-related mortality. CONCLUSIONS: IMHBs with DM have a considerably better prognosis and serum MMP-9 level appear to be a potential biomarker to predict the disease progression. ULP development (during the acute phase) and CRP levels are also associated with an elevated risk for aorta-related mortality.

Large zooming range adaptive microscope employing tunable objective and eyepiece.

The conventional microscope has discrete magnification and slow response time in zoom process, which is difficult to capture the dynamic activity of the live specimen. We demonstrate an adaptive microscope employing a tunable objective and a tunable eyepiece with large zooming range. The tunable objective consists of three glass lenses and four electrowetting liquid lenses. The tunable eyepiece consists of an achromatic eyepiece and an electrowetting liquid lens. The focal point between the objective and the eyepiece is designed to be tunable, which are controlled by voltages. Thus, the tuning range is relatively large. We fabricate the adaptive microscope and observe the specimen. In the experiment, the magnification of the microscope changes continuously from ~ 59.1 × to ~ 159.2 × , and the largest numerical aperture is ~ 0.212. The tunable eyepiece can release the back focal length of the tunable objective, which increases the zoom range of the microscope. No mechanical movement is required and the aberrations can be corrected over a wide wavelength range. Thus, the proposed adaptive microscope has a potential application in biological research and clinical medical examination.

Outcomes of type A intramural hematoma: Influence of diabetes mellitus.

OBJECTIVES: We aimed to investigate whether uncomplicated type A intramural hematoma (IMHA) patients with type 2 diabetes mellitus (DM) who underwent a "wait-and-watch strategy" and tight glycemic control had similar clinical outcomes as patients without DM who received the same treatment strategy. METHODS: Between January 2010 and December 2016, uncomplicated IMHA patients with and without diabetes mellitus were included and were propensity score-matched to improve the balance between the two groups. Cox proportional hazard models were constructed to identify the specific factors associated with aorta-related mortality. The Fine-Gray model for the competing risk analysis was used to estimate the aorta-related and nonaorta-related mortality in different groups during the follow-up period. RESULTS: A total of 109 IMHA patients were included in this study, and 66 patients were included after matching. Patients without DM experienced significantly more aorta-related adverse events (51.6% vs 13.3%; P = .001) and reinterventions than patients in the DM group (29.0% vs 6.7%; P = .023). Cox regression analysis revealed that a higher matrix metalloproteinase-9 level (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.39-2.09; P < .001) and larger maximum aortic diameter (HR, 1.41; 95% CI, 1.11-1.80; P = .005) were associated with higher aorta-related mortality. The competing risk analysis revealed a significantly higher aorta-related mortality during the follow-up period in the no DM group than in the DM group (36.4%; 95% CI, 11.6%-82.3%; P = .0294). CONCLUSIONS: Uncomplicated IMHA patients with DM (receiving the "wait-and-watch strategy" and tight glycemic control) may have lower aorta-related mortality and rates of aorta-related adverse events and reinterventions than the no DM group.

The evolution of treatments for uncomplicated type B intramural hematoma patients.

OBJECTIVES: We aimed to investigate whether uncomplicated type B intramural hematoma (IMHB) patients with known evolution predictors could benefit from more aggressive therapy. METHODS: Retrospective analysis was performed in uncomplicated IMHB patients with evolution predictors between January 2001 and August 2018. Cox proportional hazard models were constructed to identify the specific factors associated with aorta-related mortality. RESULTS: A total of 226 uncomplicated acute IMHB patients with evolution predictors were included. The conventional therapy group included 187 patients, and the other 39 patients received the more aggressive therapy. Aorta-related mortality in the first year was higher in the conventional therapy group than in the more aggressive therapy group (15% vs 2.5%, P = .035), and more patients died after thoracic endovascular aortic repair (TEVAR) (13 of 27 patients, 48.1% vs 2.5%, P < .001). The more aggressive therapy group had a higher rate of hematoma resolution than the conventional therapy group (81.6% vs 62.2%, P = .024), a lower possibility of hematoma worsening (2.6% vs 17.0%, P = .021), and a lower reintervention rate (0% vs 11.9%, P = .028). Cox regression analysis revealed that a higher rate of focal intimal disruption (FID) development (hazard ratio [HR], 3.99; 95% confidence interval [CI], 1.16-11.46, P = .010), and a higher C-reactive protein (CRP) level (HR, 1.27; 95% CI, 1.16-1.40, P < .001) were associated with increased aorta-related mortality. CONCLUSIONS: More aggressive therapy for uncomplicated IMHB patients with evolution predictors during the acute phase may result in better clinical outcomes. A higher rate of FID development and a higher CRP level are associated with increased aorta-related mortality.

Certain aortic geometries and hemodynamics are associated with FID development and impact the evolution of uncomplicated type B intramural hematoma during the acute phase.

OBJECTIVES: It is difficult to predict the evolution of uncomplicated type B intramural hematoma (IMHB) with a focal intimal disruption (FID) in the acute phase. The aims of this study were to investigate the predictors of FIDs and summarize the risk factors for the evolution of uncomplicated IMHB in the acute phase. METHODS: Eighty-six patients with uncomplicated IMHB were included and were divided according to the development of an FID during the acute phase: the FID group (n = 32) and the no-FID group (n = 54). Geometric measurements and computed fluid dynamic calculations were based on a computed tomography scan performed on admission. Multivariate logistic regression analysis was used to estimate the predictors of FID development. RESULTS: Thirty-two (37%) patients developed an FID. Patients with an FID had higher C-reactive protein levels (18.6 ± 2.3 vs 8.1 ± 0.2 mg/dL, P < 0.001) and white blood cell counts (10.3 ± 2.1 vs 7.5 ± 1.7 109 /L, P < 0.001). The no-FID group had lower occurrences of disease progression (15% vs 64%, P < 0.001) and aorta-related mortality (6% vs 25%, P = 0.016). Multivariate logistic regression analysis indicated a significant risk for the occurrence of an FID with a larger maximum aortic diameter (OR, 1.35; 95% CI, 1.05-1.73, P = 0.020), thicker hematoma (OR, 2.20; 95% CI, 1.40-3.48, P = 0.001), and higher oscillatory shear index (per 0.01 unit, OR, 1.74; 95% CI, 1.21-2.49, P = 0.003). The aorta-related mortality during the acute phase was 25% (n = 8). CONCLUSIONS: Certain aortic conditions, including ta larger aortic diameter, thicker hematoma and higher oscillatory shear stress, are associated with the FID development and result in worse clinical outcomes.

Synthesis and biological evaluation of N-glucosyl indole derivatives as sodium-dependent glucose co-transporter 2 inhibitors.

Sodium-dependent glucose co-transporter 2 (SGLT2) inhibition has been demonstrated to efficiently control hyperglycemia via an insulin secretion-independent pathway. The unique mode of action eliminates the risk of hypoglycemia and makes SGLT2 inhibitors an attractive option for the treatment of type 2 diabetes. In a continuation of our previous studies on SGLT2 inhibitors bearing different sugar moieties, sixteen new N-glucosyl indole derivatives were designed, synthesized, and evaluated for their inhibitory activity against hSGLT2. Of these sixteen, acethydrazide-containing N-glucosyl indole 9d was found to be the most potent SGLT2 inhibitor, and caused a significant elevation in urine glucose excretion in rats at 50 mg/kg, relative to the vehicle control.

[Properties of decellularized rabbit carotid artery with two different cross-linked technologies: A comparative study].

OBJECTIVE: To compare the properties between decellularized rabbit carotid artery with different cross-linked technologies.
 Methods: The decellularized rabbit carotid arteries were randomly divided into a photo-oxidation group and a procyanidins group. One group was cross-linked with photo-oxidation and the other group was cross-linked with procyanidins. The in vitro or in vivo properties of the two groups were evaluated by testing heat-shrinking temperature, max tensile strength and the max elongation or by testing tissue structure, inflammatory reaction and calcification degree.
 Results: The heat-shrinking temperature, max tensile strength and the max elongation were similar in the two groups (P>0.05). The tissue structure and inflammatory reaction were also similar in the two groups. Although the result of Von-Kossa calcium salt stain was slightly different, the calcium content was lower in the procyanidins group than that in the photo-oxidation group (P<0.05).
 Conclusion: The grafts by two cross-linked technologies show excellent mechanical capability, lower immunogenicity, good biological stability and anti-calcification ability. The procyanidins group shows a better anti-calcification property than the photo-oxidation group.

A New Concept of the Old Inhibitor NSC 74859 in Alleviating Cardiac Allograft Rejection and Extending Allograft Survival in Mice.

BACKGROUND STAT1/4 has been suggested to be involved in cardiac allograft rejection. However, no direct evidence regarding STAT3 has been established in cardiac allograft rejection. Here, we hypothesized that inhibition of STAT3 attenuates cardiac allograft rejection. MATERIAL AND METHODS To test our hypothesis, homotopic mouse heart transplantation was carried out in syngeneic C57BL/6 to C57BL/6 strain mice with or without oral gavage with NSC 74859, an inhibitor of STAT3. The immune response was investigated using real-time PCR for CD4 and CD8 surface makers of T cells and CD14 of monocytes and cytokines, including IL-2, IL-15, and IL-6 of allografts at 3, 6, and 9 days after transplantation. Prognosis was also evaluated. RESULTS We found that allografts with oral gavage of NSC 74859 whose CD4, CD8 T, and CD14 monocytes were significantly lower than that of allograft without oral gavage of NSC 74859, and the same was true for the expression of IL-2, IL-15, and IL-6. Immunohistochemical analysis of grafts showed reduced infiltration of monocytes/macrophages into the graft myocardium. Survival was also markedly extended in the NSC 74859 group. CONCLUSIONS Inhibition of IL-6/STAT3 using NSC 74859 was shown to remarkably alleviate cardiac allograft rejection in mice, indicating that the target against IL-6/STAT3 pathway might be clinically used as an alternative therapy for cardiac allograft rejection.

Design, Synthesis, and Evaluation of Thiazolidine-2,4-dione Derivatives as a Novel Class of Glutaminase Inhibitors.

Humans have two glutaminase genes, GLS (GLS1) and GLS2, each of which has two alternative transcripts: the kidney isoform (KGA) and glutaminase C (GAC) for GLS, and the liver isoform (LGA) and glutaminase B (GAB) for GLS2. Initial hit compound (Z)-5-((1-(4-bromophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)thiazolidine-2,4-dione (2), a thiazolidine-2,4-dione, was obtained from a high throughput screening of 40 000 compounds against KGA. Subsequently, a series of thiazolidine-2,4-dione derivatives was synthesized. Most of these were found to inhibit KGA and GAC with comparable activities, were less potent inhibitors of GAB, and were moderately selective for GLS1 over GLS2. The relationships between chemical structure, activity, and selectivity were investigated. The lead compounds obtained were found to (1) offer in vitro cellular activities for inhibiting cell growth, clonogenicity, and cellular glutamate production, (2) exhibit high concentrations of exposure in plasma by a pharmacokinetic study, and (3) reduce the tumor size of xenografted human pancreatic AsPC-1 carcinoma cells in mice.