[Retracted] MicroRNA­365b­3p represses the proliferation and promotes the apoptosis of non­small cell lung cancer cells by targeting PPP5C.

[This retracts the article DOI: 10.3892/ol.2021.12650.].

Structural optimization and in vivo evaluation of a colorectal stent with anti-migration and anti-tumor properties.

Clinically, colorectal stents can only palliatively relieve obstruction caused by colorectal cancer (CRC), with a high incidence of stent migration and tumor-related re-obstruction. To overcome these shortcomings, we developed a colorectal stent composed of a structure-optimized nitinol braided stent and a tubular film including an inner layer of poly (ethylene-co-vinyl acetate) (EVA) and a segmental outer layer of EVA with paclitaxel (PTX). The braiding pattern, segment number, and end shape of the stent were optimized based on the mechanical properties, ex vivo and in vivo anti-migration performance, and tissue response of the stent. The optimized nitinol stent had a structure of one middle segment in a hook-pattern and two end segments in a cross-pattern with two studs on each end in a staggered arrangement. Structure-optimized colorectal stents were prepared and evaluated in vivo. PTX released from the stent was mostly distributed in the rabbit rectum in contact with it. The biosafety of the colorectal stent was evaluated using blood tests, biochemical analysis, anatomical observation, and pathological analysis. The anti-tumor effect of the stent was also evaluated by endoscopy, anatomical observation, and pathological and immunohistochemical analyses in rabbits with orthotopic CRC. The results demonstrate that the optimized colorectal stents have effective anti-migration ability and anti-tumor effects with good biosafety. STATEMENT OF SIGNIFICANCE: In order to overcome the most common disadvantages of migration and re-obstruction of colorectal stents clinically, a colorectal stent composed of a structure-optimized nitinol stent and a tubular film including an inner layer of EVA and a segmental outer layer of EVA with PTX was put forward in this study. The optimized nitinol stent had a structure of one middle segment in hook-pattern and two end segments in cross-pattern with two studs on each end in staggered arrangement. The resulting colorectal stent has been proved with good anti-migration ability, anti-tumor effects, and biosafety in vivo, which provides a safe and effective potential treatment modality for patients with colorectal cancer.

Liver tumor segmentation and classification using FLAS-UNet++ and an improved DenseNet.

BACKGROUND: The incidence of liver tumors is among the top three in China. The treatments of benign and malignant tumors are different. Accurate diagnosis plays an important role in guiding the treatment of tumors. OBJECTIVE: The aim of this study is to solve the following: (1) blurred boundary between the liver tumor and other organs causes incorrect segmentation of liver tumor boundaries; (2) large difference in tumor size and the diversity in texture and grayscale are major challenges in liver tumor classification tasks. METHODS: Firstly, the liver tumor is segmented from the original CT images by a tumor segmentation network, UNet++ with fusion loss and atrous spatial pyramid pooling (FLAS-UNet++). The proposed segmentation method can solve the problem of tumor edge segmentation error by learning the tumor edge information. Secondly they are adaptively cropped according to the tumor volume to reduce the over-fitting and over-sensitivity of the deep network. Thirdly an improved Dense Block is designed to pay more attention to the changes in grayscale and texture between benign and malignant tumors. Finally, the features extracted from the network combined with tumor volume, patient's sex and age, are sent to a classifier for diagnosis. RESULT: Liver tumor segmentation results show that the dice, HD95 reached 71.9%, 12.1 mm, respectively. The classification results show that the accuracy, specificity, sensitivity and area under curve reached 82.4%, 79.8%, 84.4%, 87.5%, respectively. The segmentation and classification results are both better than other's methods and mainstream networks. CONCLUSIONS: In order to solve existing problems of liver tumor CT image classification methods, our method realizes the accurate segmentation and classification of liver tumors in CT images and has important clinical application value.

[Texture filtering based unsupervised registration methods and its application in liver computed tomography images].

Image registration is of great clinical importance in computer aided diagnosis and surgical planning of liver diseases. Deep learning-based registration methods endow liver computed tomography (CT) image registration with characteristics of real-time and high accuracy. However, existing methods in registering images with large displacement and deformation are faced with the challenge of the texture information variation of the registered image, resulting in subsequent erroneous image processing and clinical diagnosis. To this end, a novel unsupervised registration method based on the texture filtering is proposed in this paper to realize liver CT image registration. Firstly, the texture filtering algorithm based on L0 gradient minimization eliminates the texture information of liver surface in CT images, so that the registration process can only refer to the spatial structure information of two images for registration, thus solving the problem of texture variation. Then, we adopt the cascaded network to register images with large displacement and large deformation, and progressively align the fixed image with the moving one in the spatial structure. In addition, a new registration metric, the histogram correlation coefficient, is proposed to measure the degree of texture variation after registration. Experimental results show that our proposed method achieves high registration accuracy, effectively solves the problem of texture variation in the cascaded network, and improves the registration performance in terms of spatial structure correspondence and anti-folding capability. Therefore, our method helps to improve the performance of medical image registration, and make the registration safely and reliably applied in the computer-aided diagnosis and surgical planning of liver diseases.

A cascade-network framework for integrated registration of liver DCE-MR images.

Registration of hepatic dynamic contrast-enhanced magnetic resonance images (DCE-MRIs) is an important task for evaluation of transarterial chemoembolization (TACE) or radiofrequency ablation by quantifying enhancing viable residue tumor against necrosis. However, intensity changes due to contrast agents combined with spatial deformations render technical challenges for accurate registration of DCE-MRI, and traditional deformable registration methods using mutual information are often computationally intensive in order to tolerate such intensity enhancement and shape deformation variability. To address this problem, we propose a cascade network framework composed of a de-enhancement network (DE-Net) and a registration network (Reg-Net) to first remove contrast enhancement effects and then register the liver images in different phases. In experiments, we used DCE-MRI series of 97 patients from Renji Hospital of Shanghai Jiaotong University and registered the arterial phase and the portal venous phase images onto the pre-contrast phases. The performance of the cascade network framework was compared with that of the traditional registration method SyN in the ANTs toolkit and Reg-Net without DE-Net. The results showed that the proposed method achieved comparable registration performance with SyN but significantly improved the efficiency.

MicroRNA-365b-3p represses the proliferation and promotes the apoptosis of non-small cell lung cancer cells by targeting PPP5C.

MicroRNA (miR)-365b-3p has been recently reported to induce cell cycle arrest and apoptosis in retinoblastoma; however, its expression pattern and biological function in non-small cell lung cancer (NSCLC) remain unknown. The present study aimed to investigate the functional role of miR-365b-3p in NSCLC. The results demonstrated that miR-365b-3p expression level was significantly decreased in NSCLC tissues and cell lines compared with controls using reverse transcriptase quantitative PCR. Furthermore, miR-365b-3p expression level was overexpressed by miR-365b-3p mimics transfection in A549 cells, whereas it was downregulated following H1299 cell transfection with miR-365b-3p inhibitor. Restoration of miR-365b-3p inhibited cell proliferation, induced cell cycle G0/G1 arrest and stimulated apoptosis in A549 cells using CCK-8 assay, colony formation and flow cytometry assay. However, miR-365b-3p inhibitor had the opposite effects in H1299 cells. Furthermore, results from bioinformatics analysis and luciferase reporter assay confirmed that serine/threonine protein phosphatase 5 (PPP5C) was a direct target of miR-365b-3p. In addition, online Kaplan-Meier plotter software demonstrated that high PPP5C expression level was associated with lower overall survival and disease-free survival in patients with NSCLC. Furthermore, PPP5C knockdown imitated the effects of miR-365b-3p mimics on A549 cell proliferation, cell cycle distribution and apoptosis, whereas its overexpression rescued the effects of miR-365b-3p mimics on A549 cell proliferation, cell cycle distribution and apoptosis. In conclusion, the findings from the present study suggested that miR-365b-3p may partly suppress NSCLC cell behaviors by targeting PPP5C, which may represent a promising therapeutic target for patients with NSCLC.

Effectiveness of Infliximab on Deep Radiological Remission in Chinese Patients with Perianal Fistulizing Crohn's Disease.

BACKGROUND AND AIMS: Information concerning deep radiological healing of perianal fistulas in Chinese patients with CD is limited. The present study aimed to establish the effectiveness of infliximab on CD-related perianal fistulas using magnetic resonance imaging (MRI) and identify predictors of deep radiological remission of fistulas. METHODS: We retrospectively reviewed patients with CD with draining perianal fistulas treated with infliximab and included only those who underwent clinical assessment and MRI before and after infliximab therapy. RESULTS: Among 178 patients who underwent repeated MRI and clinical assessment, 65.2% had complex fistulas. Post-infliximab therapy, 55.1% of patients with perianal fistulizing CD showed clinical remission and 26.4% presented a clinical response; 38.2% had deep radiological remission, and 34.3% had a partial response based on the Ng score; the Van Assche scores decreased obviously compared with baseline. Prolonged infliximab infusion (18 times) presented higher radiological remission rates in patients with CD with complex fistulas. Concomitant treatment with azathioprine increased the fistula healing rate compared with infliximab alone (50% vs. 36.9%, P < 0.001). Younger age at diagnosis of CD, proctitis and requiring perianal surgery were identified as predictors of poor deep radiological remission of fistulas. Eight of ten patients who stopped infliximab and switched to an alternative agent retained a status of fistula healing in the first year of follow-up. CONCLUSIONS: Infliximab induced deep radiological remission of perianal fistulas in Chinese patients with CD. Routine MRI should be used to monitor fistula healing. Patients with younger age at diagnosis of CD, proctitis, and/or requiring perianal surgery should receive combined therapy and careful monitoring.

Efficacy of early intervention on the bowel damage and intestinal surgery of Crohn's disease, based on the Lémann index.

BACKGROUND: Clinicians aim to prevent progression of Crohn's disease (CD); however, many patients require surgical resection because of cumulative bowel damage. The aim of this study was to evaluate the impact of early intervention on bowel damage in patients with CD using the Lémann Index and to identify bowel resection predictors. METHODS: We analyzed consecutive patients with CD retrospectively. The Lémann Index was determined at the point of inclusion and at follow-up termination. The Paris definition was used to subdivide patients into early and late CD groups. RESULTS: We included 154 patients, comprising 70 with early CD and 84 with late CD. After follow-up for 17.0 months, more patients experienced a decrease in the Lémann Index (61.4% vs. 42.9%), and fewer patients showed an increase in the Lémann Index (20% vs. 35.7%) in the early compared with the late CD group. Infliximab and other therapies reversed bowel damage to a greater extent in early CD patients than in late CD patients. Twenty-two patients underwent intestinal surgery, involving 5 patients in the early CD group and 17 patients in the late CD group. Three independent predictors of bowel resection were identified: baseline Lémann index ≥ 8.99, disease behavior B1, and history of intestinal surgery. CONCLUSIONS: Early intervention within 18 months after CD diagnosis could reverse bowel damage and decrease short-term intestinal resection. Patients with CD with a history of intestinal surgery, and/or a Lémann index > 8.99 should be treated aggressively and monitored carefully to prevent progressive bowel damage.

Fracture Characteristics and Analysis in Dissimilar Cu-Al Alloy Joints Formed via Electromagnetic Pulse Welding.

The aim of this study was to identify and analyze the fatigue fracture characteristics of dissimilar Al 6061 to Cu (UNS C11000) lap joints made with ultrafast electromagnetic pulse welding (EMPW) via fractography, stress analysis and finite element simulation. It was observed that EMPW generated an annular (or ring-shaped) bonding area, with weld zones and a central non-weld zone when viewed from the cross section. Two types of failure modes occurred in relation to the cyclic loading levels: base metal fracture or transverse through-thickness (TTT) crack growth at a higher loading level, and joint interfacial failure at a lower loading level. In the interfacial failure, fatigue crack initiated from the outer edge of annular welding area, and propagated to form an approximate elliptical boundary. Fatigue crack propagation was characterized by fatigue striations existing in discrete areas on the fracture surface. This was attributed to a coupled role of shear and normal stresses present in a tensile lap shear sample due to the bending moment caused by the inherent misalignment. The final rapid fracture started from elliptical boundary with elongated shear dimples. Both theoretical stress analysis and finite element model revealed the maximum stress and stress concentration along the outer edge, where fatigue crack initiation occurred.

Angiotensin-converting enzyme 2 regulates autophagy in acute lung injury through AMPK/mTOR signaling.

Autophagy exerts a dual role in promoting cell death or survival. Recent studies have shown that it may play an important role in lipopolysaccharide (LPS)-induced acute lung injury (ALI). It was also suggested that angiotensin converting enzyme 2 (ACE2) may participate in the regulation of autophagy. The present study aims to investigate the role of autophagy in ALI and the involvement of ACE2. The regulation of the APMK/mTOR pathway was explored to clarify the underlying mechanism. The results showed that autophagy played an important role in ALI induced by LPS, as the autophagy inhibitor 3-methyladenine (3-MA) mitigated the severity of ALI. ACE2 activator resorcinolnaphthalein and inhibitor MLN-4760 significantly affected the histological appearance and wet/dry (W/D) ratio of the lung and altered the ACE2 activity of the lung, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) levels in lung tissue. Furthermore, LPS, resorcinolnaphthalein and MLN-4760 significantly affected the expression of autophagy proteins Beclin-1, LC3-I and LC3-II. To explore the mechanism of ACE2 on lung autophagy, we measured the phosphorylation of AMPK/mTOR after mice were treated with LPS and resorcinolnaphthalein or MLN-4760. The results revealed that resorcinolnaphthalein and MLN-4760 both significantly altered the phosphorylation of AMPK/mTOR. Finally, we found that AMPK inhibitor (8-bAMP) and mTOR activator (propranolol) both abolished the effects of ACE2 activator (resorcinolnaphthalein) on the expression of lung autophagy proteins Beclin-1, LC3-I and LC3-II. In conclusion, these findings suggest that ACE2 could alleviate the severity of ALI, inflammation and autophagy in lung tissue through the AMPK/mTOR pathway.