Overexpression of SEZ6L2 and Immune Infiltration in Cancer Based on Gene Image Diagnosis.

BACKGROUND: With the rapid advancement of optical image diagnostic technology, researchers are delving into the potential applications in the field of cancer diagnosis and treatment. The exact link between the SEZ6L2 gene and cancer immune infiltration remains elusive. MATERIALS AND METHODS: This study aims to investigate the relationship between SEZ6L2 gene overexpression and cancer immune infiltration using optical image diagnostic technology, thereby presenting novel insights for enhancing cancer diagnosis and treatment strategies. Tissue samples obtained from cancer patients were meticulously analyzed to quantitatively assess the expression of the SEZ6L2 gene through light image diagnostic technology. Additionally, immunohistochemical techniques were employed to assess the nature and quantity of immune infiltrating cells within the cancerous tissues. RESULTS: The enrichment pathways were found to include complement activation, circulating immunoglobulin mediated humoral immune response, protein activation cascade, immunoglobulin complex, and immunoglobulin. In addition, the expression of SEZ6L2 is closely related to the infiltration level of tumor infiltrating immune cells (TIICs), and there is a potential relationship between the expression of SEZ6L2 and different marker genes of TIIC. CONCLUSION: Increased SEZ6L2 mRNA expression in breast invasive carcinoma was significantly associated with negative prognosis and immune invasion. SEZ6L2 may be a novel prognostic biomarker and a potential immunotherapeutic target in BRCA.

The short-term outcomes and risk factors of post-myocardial infarction ventricular septal rupture: a multi-center retrospective Study.

OBJECTIVES: Post-myocardial infarction ventricular septal rupture (PIVSR) is one of the most severe types of mechanical complications after acute myocardial infarction (AMI) with high mortality and poor prognosis. The risk factors for short-term mortality of patients with PIVSR may be not widely recognized. We aimed to assess the prevalence and short-term mortality risk predictors of PIVSR. METHODS: A total of 62 patients with a diagnosis of PIVSR were admitted to three top general public hospitals in Chongqing, China. Clinical characteristics and short-term outcomes of patients with PIVSR were compared. Predictors of PIVSR were assessed using logistic regression analysis. RESULTS: Mean age was 70.7 ± 10.7 years (38.7% female). The overall in-hospital mortality of PIVSR remained high (71%). Most (47/62) of the patients were in Killip class III or IV at the time of rupture diagnosis. Logistic regression analysis revealed that white blood cell count (WBC, OR 1.619, 95% CI 1.172-2.237, P = 0.005), cardiogenic shock (OR 47.706, 95%CI 2.859-795.945, P = 0.007) and left ventricular ejection fraction (LVEF, OR 0.803, 95%CI 0.689-0.936, P = 0.009) were independent risk factors of in-hospital early mortality. The nomogram developed for predicting the risk of short-term mortality showed a robust discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.956 (95%CI 0.912-1.000). CONCLUSION: The short-term mortality of PIVSR remained high. WBC, cardiogenic shock, and LVEF were the independent predictive factors of short-term mortality. Our nomogram might be used to predict early mortality of patients with PIVSR.

Preoperative fibrinogen level predicts the risk and prognosis of patients with native valve infective endocarditis undergoing valve surgery.

Aim: The aim of this study was to assess the clinical significance and prognostic value of the preoperative fibrinogen (FBG) level in patients with native valve infective endocarditis (NVIE) who underwent valve surgery. Methods: This retrospective study included a total of 163 consecutive patients who were diagnosed with NVIE and underwent valve surgery from January 2019 to January 2022 in our hospital. The primary endpoint was all-cause mortality. Results: All-cause mortality was observed in 9.2% of the patients (n = 15). Body mass index (BMI) was lower in the survival group (p = 0.025), whereas FBG (p = 0.008) and platelet count (p = 0.044) were significantly greater in the survival group than in the death group. Multivariate Cox proportional hazards analysis revealed that FBG (HR, 0.55; 95% CI, [0.32-0.94]; p = 0.029) was an independent prognostic factor for all-cause mortality. Furthermore, Kaplan‒Meier survival curve analysis revealed that patients with low FBG levels (<3.28 g/L) had a significantly greater mortality rate (p = 0.034) than did those with high FBG levels (>3.99 g/L). In the trend analysis, the FBG tertiles were significantly related to all-cause mortality in all three adjusted models, and the p values for trend were 0.017, 0.016, and 0.028, respectively. Conclusion: Preoperative FBG may serve as a prognostic factor for all-cause mortality, and an FBG concentration less than 3.28 g/L was associated with a greater risk of all-cause mortality in NVIE patients undergoing valve surgery.

Description and Prognosis of Patients with Recovered Dilated Cardiomyopathy: A Retrospective Cohort Study.

Background: With the recent advances in the treatment of heart failure (HF), it is intriguing that a very small number of patients with dilated cardiomyopathy (DCM) have been observed as being fully recovered. However, knowledge of the progression and prognosis of patients with recovered DCM remains sparse. Herein, we conducted this study to investigate the clinical characteristics and prognosis of patients with recovered DCM. Methods: Consecutive patients with recovered DCM referred to our hospital between March 2009 and May 2021 were included. The recovered DCM patients were categorized into relapse and non-relapse groups. The primary endpoint was all-cause death, and the secondary endpoint was HF re-hospitalization during follow-up. Multivariate analyses were performed to identify predictors of relapse among recovered DCM patients. Kaplan-Meier analyses were used to assess the prognostic significance of relapse. Results: A comparatively large cohort of 122 recovered DCM patients from 10,029 DCM patients was analyzed. During a median follow-up duration of 53.5 months, the relapse rate among recovered DCM patients was 15.6% (19/122). Age (odds ratio, OR 1.079, 95% confidence interval, CI: 1.014-1.148; p = 0.017), systolic blood pressure (SBP) at diagnosis (OR 0.948, 95% CI: 0.908-0.990; p = 0.015) and changes in left ventricular ejection fraction from diagnosis to recovery ( Δ LVEF) (OR 0.898, 95% CI: 0.825-0.978; p = 0.013) were identified as predictors of relapse. Furthermore, among 122 patients, 5 (4.1%) experienced death, and 12 (9.8%) underwent HF re-hospitalization. Four deaths occurred in the relapse group, with one in the non-relapse group. All deaths were attributed to cardiovascular events. The long-term prognosis of the relapse group was significantly worse compared to the non-relapse group by Kaplan-Meier analysis (p < 0.001 based on the log-rank test). Multivariate analyses significantly associated relapse with all-cause mortality in recovered DCM patients (hazard ratio, HR 7.738, 95% CI: 1.892-31.636; p = 0.004). Conclusions: Recovered DCM patients are at risk of relapse. Older age, lower SBP, and smaller Δ LVEF were independently associated with relapse in recovered DCM patients. Relapse after recovery was related to an unfavorable long-term prognosis.

MAS-CL: An End-to-End Multi-Atlas Supervised Contrastive Learning Framework for Brain ROI Segmentation.

Brain region-of-interest (ROI) segmentation with magnetic resonance (MR) images is a basic prerequisite step for brain analysis. The main problem with using deep learning for brain ROI segmentation is the lack of sufficient annotated data. To address this issue, in this paper, we propose a simple multi-atlas supervised contrastive learning framework (MAS-CL) for brain ROI segmentation with MR images in an end-to-end manner. Specifically, our MAS-CL framework mainly consists of two steps, including 1) a multi-atlas supervised contrastive learning method to learn the latent representation using a limited amount of voxel-level labeling brain MR images, and 2) brain ROI segmentation based on the pre-trained backbone using our MSA-CL method. Specifically, different from traditional contrastive learning, in our proposed method, we use multi-atlas supervised information to pre-train the backbone for learning the latent representation of input MR image, i.e., the correlation of each sample pair is defined by using the label maps of input MR image and atlas images. Then, we extend the pre-trained backbone to segment brain ROI with MR images. We perform our proposed MAS-CL framework with five segmentation methods on LONI-LPBA40, IXI, OASIS, ADNI, and CC359 datasets for brain ROI segmentation with MR images. Various experimental results suggested that our proposed MAS-CL framework can significantly improve the segmentation performance on these five datasets.

Sodium-glucose cotransporter 2 inhibitors attenuate vascular calcification by suppressing endoplasmic reticulum protein thioredoxin domain containing 5 dependent osteogenic reprogramming.

AIMS: Vascular calcification is strongly linked to the development of major adverse cardiovascular events, but effective treatments are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging category of oral hypoglycemic drugs that have displayed marked effects on metabolic and cardiovascular diseases, including recently reported vascular medial calcification. However, the roles and underlying mechanisms of SGLT2 inhibitors in vascular calcification have not been fully elucidated. Thus, we aimed to further determine whether SGLT2 inhibitors protect against vascular calcification and to investigate the mechanisms involved. METHODS AND RESULTS: A computed tomography angiography investigation of coronary arteries from 1554 patients with type 2 diabetes revealed that SGLT2 inhibitor use was correlated with a lower Agatston calcification score. In the vitamin D3 overdose, 5/6 nephrectomy chronic kidney disease-induced medial calcification and Western diet-induced atherosclerotic intimal calcification models, dapagliflozin (DAPA) substantially alleviated vascular calcification in the aorta. Furthermore, we showed that DAPA reduced vascular calcification via Runx2-dependent osteogenic transdifferentiation in vascular smooth muscle cells (VSMCs). Transcriptome profiling revealed that thioredoxin domain containing 5 (TXNDC5) was involved in the attenuation of vascular calcification by DAPA. Rescue experiments showed that DAPA-induced TXNDC5 downregulation in VSMCs blocked the protective effect on vascular calcification. Furthermore, TXNDC5 downregulation disrupted protein folding-dependent Runx2 stability and promoted subsequent proteasomal degradation. Moreover, DAPA downregulated TXNDC5 expression via amelioration of oxidative stress and ATF6-dependent endoplasmic reticulum stress. Consistently, the class effects of SGLT2 inhibitors on vascular calcification were validated with empagliflozin in intimal and medial calcification models. CONCLUSIONS: SGLT2 inhibitors ameliorate vascular calcification through blocking endoplasmic reticulum stress-dependent TXNDC5 upregulation and promoting subsequent Runx2 proteasomal degradation, suggesting that SGLT2 inhibitors are potentially beneficial for vascular calcification treatment and prevention.

Anomalous origin of the coronary artery: prevalence and coronary artery disease in adults undergoing coronary tomographic angiography.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital coronary anomaly with the potential to cause adverse cardiac events. However, there is limited data on the association between AAOCA and coronary artery disease (CAD). Therefore, the aim of this study is to determine the prevalence and symptoms of patients with AAOCA, as well as investigate the correlation between AAOCA and CAD in a population referred for coronary computed tomographic angiography (CTA). METHODS AND RESULTS: All consecutive patients who underwent CTA from 2010 to 2021 were included. Characteristics, symptoms, coronary related adverse events and CTA information were reviewed by medical records. Separate multivariable cumulative logistic regressions were performed, using the stenosis severity in each of the four coronaries as individual responses and as a combined patient clustered response. Finally, we identified 207 adult patients with AAOCA, the prevalence of AAOCA is 0.23% (207/90,501). Moreover, this study found no significant association between AAOCA and CAD. AAOCA did not contribute to higher rates of hospitalization or adverse cardiac events, including calcification. CONCLUSION: AAOCA is a rare congenital disease that is not associated with increased presence of obstructive CAD in adults.

ANXA9 facilitates S100A4 and promotes breast cancer progression through modulating STAT3 pathway.

Breast cancer has the highest global incidence and mortality rates among all cancer types. Abnormal expression of the Annexin family has been observed in different malignant tumors, including upregulated ANXA9 in breast cancer. We found highly expressed ANXA9 in metastatic breast cancer tissues, which is correlated with breast cancer progression. In vitro, the functional experiments indicated ANXA9 influenced breast cancer proliferation, motility, invasion, and apoptosis; in vivo, downregulation of ANXA9 suppressed breast cancer xenograft tumor growth and lung metastasis. Mechanically, on one side, we found that ANXA9 could mediate S100A4 and therefore regulate AKT/mTOR/STAT3 pathway to participate p53/Bcl-2 apoptosis; on the other side, we found ANXA9 transferred S100A4 from cells into the tumor microenvironment and mediated the excretion of cytokines IL-6, IL-8, CCL2, and CCL5 to participate angiogenesis via self- phosphorylation at site Ser2 and site Thr69. Our findings demonstrate significant involvement of ANXA9 in promoting breast cancer progression, thereby suggesting that therapeutic intervention via targeting ANXA9 may be effective in treating metastatic breast cancer.

MSEF-Net: Multi-scale edge fusion network for lumbosacral plexus segmentation with MR image.

Nerve damage of spine areas is a common cause of disability and paralysis. The lumbosacral plexus segmentation from magnetic resonance imaging (MRI) scans plays an important role in many computer-aided diagnoses and surgery of spinal nerve lesions. Due to the complex structure and low contrast of the lumbosacral plexus, it is difficult to delineate the regions of edges accurately. To address this issue, we propose a Multi-Scale Edge Fusion Network (MSEF-Net) to fully enhance the edge feature in the encoder and adaptively fuse multi-scale features in the decoder. Specifically, to highlight the edge structure feature, we propose an edge feature fusion module (EFFM) by combining the Sobel operator edge detection and the edge-guided attention module (EAM), respectively. To adaptively fuse the multi-scale feature map in the decoder, we introduce an adaptive multi-scale fusion module (AMSF). Our proposed MSEF-Net method was evaluated on the collected spinal MRI dataset with 89 patients (a total of 2848 MR images). Experimental results demonstrate that our MSEF-Net is effective for lumbosacral plexus segmentation with MR images, when compared with several state-of-the-art segmentation methods.

B-type natriuretic peptide levels at admission predict the prognosis of patients with infective endocarditis undergoing cardiac surgery.

Purpose: The objective of this study was to explore the relationship between elevated B-type natriuretic peptide (BNP) levels and the prognosis of patients with infective endocarditis (IE) undergoing cardiac surgery. Methods: In total, 162 IE patients with recorded BNP levels upon admission were included in the present study. The primary end point was all-cause mortality. Results: Multivariate Cox analysis revealed a significant association between log BNP and all-cause mortality. Kaplan-Meier analysis revealed a poorer prognosis for patients with BNP levels ≥ the 75th percentile. Furthermore, the linear trend test indicated a significant link between BNP quartiles and the primary end point within the models. Conclusion: Elevated BNP levels upon admission could predict all-cause mortality in IE patients undergoing cardiac surgery.

Infective endocarditis (IE) refers to an infection affecting the heart lining, heart valves or blood vessels. Despite advancements in medical and surgical interventions, the overall mortality rate remains high among IE patients after surgery. B-type natriuretic peptide (BNP) is a peptide released in response to increased stress on the ventricular and atrial walls and is commonly used as a biomarker for heart failure. This study was aimed to assess the potential of BNP in predicting all-cause mortality in IE patients. The results indicate that elevated BNP levels upon admission could predict a worse prognosis following endocarditis surgery. Additionally, elevated BNP levels upon admission were associated with an increased risk of death.

Impact of coronary artery disease in patients with hypertrophic cardiomyopathy.

BACKGROUND: Atherosclerotic coronary artery disease (CAD) often occurs concurrently with hypertrophic cardiomyopathy (HCM). However, the influence of concomitant CAD has not been fully assessed in patients with HCM. METHODS: Invasive or computed tomography coronary angiography was performed in 461 patients with HCM at our hospital to determine the presence and severity of CAD from March 2010 to April 2022. The primary end points were all-cause, cardiovascular, and sudden cardiac deaths. The survival of HCM patients with severe CAD was compared with that of HCM patients without severe CAD. RESULTS: Of 461 patients with HCM, 235 had concomitant CAD. During the median (interquartile range) follow-up of 49 (31-80) months, 75 patients (16.3%) died. The 5-year survival estimates were 64.3%, 82.5%, and 86.0% for the severe, mild-to-moderate, and no-CAD groups, respectively (log-rank, p = 0.010). Regarding the absence of cardiovascular death, the 5-year survival estimates were 68.5% for patients with severe CAD, 86.4% for patients with mild-to-moderate CAD, and 90.2% for HCM patients with no CAD (log-rank, p = 0.001). In multivariate analyses, severe CAD was associated with all-cause and cardiovascular death after adjusting for age, left ventricular ejection fraction, hypertension, and atrial fibrillation. CONCLUSIONS: This study showed a worse prognosis among HCM patients with severe CAD than among HCM patients without severe CAD. Therefore, timely recognition of severe CAD in HCM patients and appropriate treatment are important.

Characterizing the Survival-Associated Interactions Between Tumor-Infiltrating Lymphocytes and Tumors From Pathological Images and Multi-Omics Data.

The tumor-infiltrating lymphocytes (TILs) and its correlation with tumors have shown significant values in the development of cancers. Many observations indicated that the combination of the whole-slide pathological images (WSIs) and genomic data can better characterize the immunological mechanisms of TILs. However, the existing image-genomic studies evaluated the TILs by the combination of pathological image and single-type of omics data (e.g., mRNA), which is difficulty in assessing the underlying molecular processes of TILs holistically. Additionally, it is still very challenging to characterize the intersections between TILs and tumor regions in WSIs and the high dimensional genomic data also brings difficulty for the integrative analysis with WSIs. Based on the above considerations, we proposed an end-to-end deep learning framework i.e., IMO-TILs that can integrate pathological image with multi-omics data (i.e., mRNA and miRNA) to analyze TILs and explore the survival-associated interactions between TILs and tumors. Specifically, we firstly apply the graph attention network to describe the spatial interactions between TILs and tumor regions in WSIs. As to genomic data, the Concrete AutoEncoder (i.e., CAE) is adopted to select survival-associated Eigengenes from the high-dimensional multi-omics data. Finally, the deep generalized canonical correlation analysis (DGCCA) accompanied with the attention layer is implemented to fuse the image and multi-omics data for prognosis prediction of human cancers. The experimental results on three cancer cohorts derived from the Cancer Genome Atlas (TCGA) indicated that our method can both achieve higher prognosis results and identify consistent imaging and multi-omics bio-markers correlated strongly with the prognosis of human cancers.

Low-Dose CT Denoising via Sinogram Inner-Structure Transformer.

Low-Dose Computed Tomography (LDCT) technique, which reduces the radiation harm to human bodies, is now attracting increasing interest in the medical imaging field. As the image quality is degraded by low dose radiation, LDCT exams require specialized reconstruction methods or denoising algorithms. However, most of the recent effective methods overlook the inner-structure of the original projection data (sinogram) which limits their denoising ability. The inner-structure of the sinogram represents special characteristics of the data in the sinogram domain. By maintaining this structure while denoising, the noise can be obviously restrained. Therefore, we propose an LDCT denoising network namely Sinogram Inner-Structure Transformer (SIST) to reduce the noise by utilizing the inner-structure in the sinogram domain. Specifically, we study the CT imaging mechanism and statistical characteristics of sinogram to design the sinogram inner-structure loss including the global and local inner-structure for restoring high-quality CT images. Besides, we propose a sinogram transformer module to better extract sinogram features. The transformer architecture using a self-attention mechanism can exploit interrelations between projections of different view angles, which achieves an outstanding performance in sinogram denoising. Furthermore, in order to improve the performance in the image domain, we propose the image reconstruction module to complementarily denoise both in the sinogram and image domain.

Residual-atrous attention network for lumbosacral plexus segmentation with MR image.

Accurate segmentation of the lumbosacral plexus is a crucial step for diagnosis and analysis of nerve damage in clinical. Due to the extremely low contrast and complicated structure around the lumbosacral plexus, it has been remaining a challenging task to effectively segment the lumbosacral plexus from spinal MR images. Even though several deep learning methods for spine segmentation have been developed, most of them only pay attention to the segmentation of vertebral bodies and intervertebral discs rather than nerves. To solve these problems, in this paper, we propose a residual-atrous attention network (RA2-Net) for lumbosacral plexus segmentation with MR images. Specifically, the RA2-Net consists of three main parts, (1) the atrous encoder module is employed to learn multi-scale contextual features from MR images in the encoder, (2) the residual skip connection operation is used to integrate the features with high-resolution spatial details in the encoder and the high-level contextual features in the decoder, and (3) the scale attention block is proposed for fusing the multi-scale high-level features in the decoder. We perform our proposed RA2-Net for the lumbosacral plexus segmentation on the collected spinal MRI dataset with 10 patients (a total of 236 MRI scans). Extensive experiments demonstrate that our RA2-Net achieves better performance in lumbosacral plexus segmentation with MR images when compared with several state-of-the-art methods.

Bombesin receptor-activated protein exacerbates cisplatin-induced AKI by regulating the degradation of SIRT2.

BACKGROUND: Acute kidney injury (AKI) is a public health problem with no specific therapies in the clinic and the underlying pathogenesis of AKI remains obscure. Bombesin receptor-activated protein (BRAP, C6ORF89 protein) was initially discovered as a ligand for a previously orphan G-protein-coupled receptor bombesin-like receptor-3. At present, accepted biological effects of BRAP include cell cycle progression, wound repair and the activation of histone deacetylases. However, its role in kidney disease is unknown. In this study we have investigated the role of BRAP and underlying mechanisms involved in cisplatin (CP)-induced AKI. METHODS: Here we used Bc004004 (homologous of C6ORF89 in mice) knockout mice and HK2 cells to investigate the effect of BRAP on AKI in vitro and in vivo. We analyzed ChIP-Seq and RNA-Seq data to search for the upstream regulators of BRAP and downstream mediators of BRAP action in AKI. Immunostaining, real-time polymerase chain reaction (PCR), co-immunoprecipitation, a dual-luciferase reporter assay and ChIP-PCR assay were applied to reveal the upstream and downstream regulation mechanism of BRAP during cisplatin-induced AKI. RESULTS: BRAP was downregulated in mice and human kidneys with AKI. Global Bc004004 deletion alleviated tubular cell apoptosis and necroptosis in CP-induced AKI mice, whereas local overexpression of BRAP in kidneys aggravated them. Pan-caspase inhibitor Z-VAD pretreatment attenuated CP-induced blood creatinine increase and kidney injury in wild-type mice but not in BRAP -/- mice. The activation of mixed lineage kinase like-domain was magnified by Z-VAD in CP-treated mice, especially in BRAP -/- mice. The cytoprotective effect of Z-VAD was more substantial than necrostatin-1 (Nec-1, an inhibitor of necroptosis) in CP-treated human kidney proximal tubular epithelial (HK2) cells. Furthermore, Nec-1 pretreatment reduced the CP-induced cell death in BRAP overexpression HK2 cells but did not work in cells with normal BRAP levels. We determined that CP treatment activated the nuclear factor-κB subunit P65 and inhibition of P65 increased the messenger RNA (mRNA) levels of BRAP in HK2 cells. The chromatin immunoprecipitation assay and dual-luciferase reporter gene assay verified P65 binding to the C6ORF89 promoter and reduced its mRNA expression upon CP treatment. Next we found that sirtuin 2 (SIRT2) was downregulated in CP-induced AKI and BRAP levels directly impacted the protein levels of SIRT2. Our findings further confirmed that BRAP regulates the SIRT2 protein levels by affecting SIRT2's interactions with E3 ubiquitin ligase HRD1 and subsequent proteasomal degradation. CONCLUSIONS: Our results demonstrated that BRAP played an important role in tubular cell apoptosis and necroptosis during CP-induced AKI. Safe and efficient BRAP inhibitors might be effective therapeutic options for AKI.

Comparison of two internal fixation systems in lumbar spondylolysis by finite element methods.

BACKGROUND AND PURPOSE: Internal fixation surgeries are currently the most effective treatments for lumbar spondylolysis, but the optimal fixation method is still on debate. This study was designed to compare the biomechanical characteristics of two fixation methods for lumbar spondylolysis, the pedicle screw-U shape rod (PSUSR) internal fixation system, and the pedicle screw-vertebral plate hook (PSVPH) internal fixation system, through three-dimensional finite element analysis, expecting to provide clinical guidance. METHODS: Four finite element models (A, B, C, D) of L4-S1 vertebral body of a female patient were reconstructed by CT image segmentation. (A: intact model. B: spondylolysis model. C: spondylolysis model with PSUSR internal fixation. D: spondylolysis model with PSVPH internal fixation). Six physiological motion states were simulated by applying 500N concentrated force and 10Nm moment load to four models. The biomechanical advantages of the two internal fixation systems were evaluated by comparing the range of motion (ROM), maximum stress, maximum strain, and maximum displacement of the models. RESULTS: Compared to model B, the ROM decreased by 35.7%-57.1% in model C and 39.7%-64.8% in model D. The maximum displacements of model C and D both decreased. The maximum stresses in both vertebral and the internal fixation system are greater in model C than those in model D. The maximum stress and strain reduction of L5-S1 intervertebral disc in model D was greater than that in model C. Model D restores the articular cartilage stresses to the normal levels of model A. The maximum stress and maximum displacement of the bone graft in model C are greater than those in model D. CONCLUSIONS: The PSVPH internal fixation system has better biomechanical properties than PSUSR internal fixation system in several mechanical comparisons. Experimental results suggest that PSVPH internal fixation system can effectively treat lumbar spondylolysis while preserving segmental mobility, and can be the treatment of choice.

A Triple-Regulated Oncolytic Adenovirus Carrying MicroRNA-143 Exhibits Potent Antitumor Efficacy in Colorectal Cancer.

The cancer-targeting gene virotherapy might be a useful strategy for the treatment of cancer, because it could combine the advantages of both gene therapy and virotherapy. This study aimed to construct a triple-regulated oncolytic adenovirus, Ad-RGD-Survivin-ZD55-miR-143, carrying the therapeutic gene miR-143 and evaluate its possible antitumor effect in colorectal cancer. We observed that miR-143 was lowly expressed in patients with colorectal cancer. The upregulation of miR-143 could inhibit cell proliferation and induce cell apoptosis by targeting KRAS in colorectal cancer cells. Then, Ad-RGD-Survivin-ZD55-miR-143 was successfully constructed in this study. Cells infected with Ad-RGD-Survivin-ZD55-miR-143 could inhibit cell proliferation, suppress cell migration and invasion, arrest cells at the G1 phase, and induce cellular apoptosis. At the same time, Ad-RGD-Survivin-ZD55-miR-143 decreased the expression of PARP-1 and KRAS protein in vitro. In a HCT116 xenograft model, intratumoral injection of Ad-RGD-Survivin-ZD55-miR-143 resulted in reduced tumor growth. Furthermore, Ad-RGD-Survivin-ZD55-miR-143 induced apoptosis and decreased the expression level of KRAS in HCT116 xenograft cells. Our results suggested that Ad-RGD-Survivin-ZD55-miR-143 produced a strong antitumor effect by targeting KRAS and that this strategy could broaden the therapeutic options for treating colorectal cancer.

Thoracic vertebra fixation with a novel screw-plate system based on computed tomography imaging and finite element method.

BACKGROUND AND OBJECTIVE: The traditional pedicle screw-rod internal fixation system has been widely used for thoracic diseases in clinical practice, but its high profile increases the damage to soft tissue, leading to long-term intractable back stiffness. The purpose of this study is to compare biomechanical advantages between the new spine pedicle screw-plate internal fixation system and traditional pedicle screw-rod internal fixation system using finite element analysis. METHODS: Based on computed tomography (CT), four three-dimensional finite element models of T7-T9 were constructed. The downward concentrated force of 150 N and the moment of 5 Nm was applied to the models to simulate six physiological activities, including flexion, extension, left and right lateral bending, left and right axial torsion. The maximum displacement, range of motion (ROM) and maximum stress of the two models in six physiological activities, was measured to evaluate the biomechanical advantages of the novel pedicle screw-plate internal fixation system. RESULTS: The novel pedicle screw-plate internal fixation system has a lower profile than the traditional pedicle screw-rod internal fixation system. With regards to the stability, the maximum displacement of the models of two internal fixation systems decreased by 56.2%-91.4% under the six motion status when comparing with the unstable model. Meanwhile, the ROM remained unchanged between the two models of internal fixation systems besides the left lateral bending. However, there is no significant difference in the ROM between the models of the two internal fixation systems in left lateral bending motion (P = 0.203). In terms of the strength, the maximum stress in the model with the new pedicle screw-plate internal fixation system was higher than that of model with the traditional pedicle screw-rod internal fixation system in every motion status but left and right lateral bending motion. CONCLUSIONS: The novel pedicle screw-plate internal fixation system has lower profile in orthopedics and higher strength, However, it has no disadvantage when comparing with the traditional pedicle screw-rod internal fixation system in terms of the stability. In summary, we suggest that the novel spine pedicle screw-plate system can be used as a new internal fixation and provide better comfort for patients.

Modelling tri-cortical pedicle screw fixation in thoracic vertebrae under osteoporotic condition: A finite element analysis based on computed tomography.

BACKGROUND AND OBJECTIVE: The technique of tri-cortical pedicle screw (TCPS) has been used to improve the anchoring strength in the sacral vertebrae. However, no studies have reported their application in the thoracic vertebrae. Our research is aimed to assess the stability and strength of the TCPS in thoracic vertebrae under osteoporotic condition by three dimensional (3D) finite element method on the basis of medical image reconstruction using computed tomography (CT), and verifying its effectiveness in clinical application. MATERIALS AND METHODS: The 3D finite element models were constructed using Mimcs to transfer two dimensional CT images into 3D models by marching cubes algorithm of six-partition. Six physiological activities were simulated in 3D finite element models. Compared with the strength and stability of the uni-cortical pedicle screw (UCPS) and bi-cortical pedicle screw (BCPS), the effectiveness of TCPS was assessed. The stress distribution and maximum stress were measured to evaluate the strength. The maximum displacement and the range of motion were analysed to assessed the stability. EXPERIMENTAL RESULTS: Four geometrically accurate and nonlinear T7-T9 finite element models were constructed successfully by 3D finite element method based on the CT images. Three kinds of internal fixation methods in the osteoporotic thoracic vertebral body can improved the maximum stress, decrease the maximum displacement and range of motion in six physiological activities. The range of motion and maximum displacement of TCPS decreased more significantly than that of UCPS and BCPS. The maximum von Mises stress of TCPS was minimum and UCPS was maximum under the condition of extension, right lateral bending, left rotation and right rotation. CONCLUSIONS: Effectively, TCPS can provide better stability and strength than that of UCPS and BCPS techniques in the osteoporotic thoracic vertebrae. In practice, the technique of TCPS can be applied in the osteoporotic thoracic vertebral body to enhance the griping strength of the screws and reduce the risk of pedicle screw loosening. However, further cadaver experiments and more biomechanical analysis are necessary to confirmed our findings.

VGLL4 interacts with STAT3 to function as a tumor suppressor in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive malignancy with a poor prognosis, and there are no effective molecular-targeted drugs for TNBC patients in clinical practice. The JAK-STAT pathway is implicated in tumorigenesis and the progression of various cancers. In this study, the results demonstrated that VGLL4 is expressed at low levels in both TNBC specimens and cell lines and that VGLL4 expression is negatively correlated with Ki67 expression and tumor size in TNBC patients. VGLL4 knockdown can promote the growth of TNBC cells, while VGLL4 overexpression significantly suppresses the growth of TNBC cells in vitro. More importantly, VGLL4 significantly inhibits tumor progression in a nude mouse model. In addition, VGLL4 is a direct target of miR-454, and the upregulation of miR-454 decreases VGLL4 expression and promotes the cell growth of TNBC cells. Furthermore, we also demonstrated that VGLL4 interacts with STAT3, the core component of the JAK-STAT pathway, leading to the inactivation of STAT3 and the inhibition of STAT3 downstream transcription. Collectively, these findings indicate that VGLL4 expression is negatively associated with poor prognosis in TNBC patients. High expression of miR-454 may be one of the causes of the downregulation of VGLL4 in TNBC, and VGLL4 acts as a tumor suppressor in TNBC by interacting with STAT3 and subsequently suppresses the STAT3 signaling axis, providing potential biomarkers and therapeutic approaches for this fatal disease.