Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways.

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKß independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.

Clinical outcomes of percutaneous microwave ablation for pulmonary oligometastases from hepatocellular carcinoma: a retrospective, multicenter study.

BACKGROUND: Pulmonary oligometastases are common in hepatocellular carcinoma (HCC), however, the existing therapeutic options have several limitations. This study aimed to assess the safety and efficacy of microwave ablation (MWA) in the treatment of HCC-originating pulmonary oligometastases. METHODS: A total of 83 patients, comprising 73 males and 10 females with a median age of 57 years, who had pulmonary oligometastases from HCC, underwent MWA treatment at four different medical institutions. Inclusion criteria for patients involved having primary HCC under control and having less than three oligometastases with a maximum diameter of ≤ 5 cm in the unilateral lung or less than five oligometastases with a maximum diameter of ≤ 3 cm in the bilateral lung. A total of 147 tumors were treated with MWA over 116 sessions. The primary endpoints assessed included technical success, treatment efficacy, and local progression rate, while secondary endpoints encompassed complications, clinical outcomes, overall survival (OS), local progression-free survival (LPFS), and prognostic factors. RESULTS: The technical success rate for MWA was 100% (116/116 sessions), and the treatment efficacy rate was 82.3% (121/147 tumors). Six months after MWA, the local progression rate was 23.1% (18/147 tumors). Complications were observed in 10.3% (major) and 47.4% (minor) of the 116 sessions, with no cases of ablation-related deaths. The median follow-up period was 21.6 months (range: 5.7-87.8 months). Median OS was 22.0 months, and the 1-, 2-, and 3-year OS rates were 82.6%, 44.5%, and 25.2%, respectively. Median LPFS was 8.5 months. Multivariate Cox regression analysis identified α-fetoprotein (AFP) levels during initial diagnosis and the number of oligometastases as potential independent prognostic factors for OS (p = 0.017 and 0.045, respectively). CONCLUSION: Percutaneous MWA is a safe and effective treatment modality for pulmonary oligometastases originating from HCC.

Apatinib weakens proliferation, migration, invasion, and angiogenesis of thyroid cancer cells through downregulating pyruvate kinase M2.

Thyroid cancer (TC) is the most frequent malignancy of the endocrine system. Apatinib, as an anti-angiogenic agent, has been applied in the therapy of several cancers. However, the function and mechanism of Apatinib in TC have not been clearly elucidated. After processing with Apatinib alone or combined PKM2 overexpression plasmids, cell proliferation, migration, and invasion were analyzed by EdU staining, CCK-8, wound healing, and Transwell. Meanwhile. HUVECs were incubated with the conditioned medium prepared from cell culture medium, and tube formation and VEGFR2 expression in HUVECs were examined using tube formation and immunofluorescence (IF) assays. Besides, we established a nude mouse xenograft model by lentivirus-mediated PKM2 shRNAs, and tested the growth of tumors; the pathological structure was analyzed with H&E staining. And the expressions of N-cadherin, Vimentin, E-cadherin, PKM2, VEGFA, VEGFR2, and Ki67 were determined by immunohistochemistry or Western blot. Apatinib could prominently suppress proliferation, migration, invasion, and HUVEC tube formation in SW579 and TPC-1 cells. Besides, we discovered that Apatinib had a significant inhibitory role on the expression of pyruvate kinase M2 (PKM2) in TC cells. And PKM2 overexpression also could notably reverse Apatinib-mediated inhibition of TC progression. Moreover, PKM2 shRNAs were applied to TC xenografts, resulting in significant reduction in tumor volume and suppression of angiogenesis-related protein expression. In summary, Apatinib has a regulatory role in TC progression, and Apatinib can block cancer cell angiogenesis by downregulating PKM2. This will provide a theoretical basis for therapy of TC.

High rumen degradable starch diet induced blood bile acids profile changes and hepatic inflammatory response in dairy goats.

The objective of this study was to reveal the effect of rumen degradable starch (RDS) on bile acid metabolism and liver transcription in dairy goats using metabolomics and transcriptomics. Eighteen Guanzhong dairy goats of a similar weight and production level (body weight = 45.8 ± 1.54 kg, milk yield = 1.75 ± 0.08 kg, and second parity) were randomly assigned to 3 treatment groups where they were fed a low RDS (LRDS, RDS = 20.52% DM) diet, medium RDS (MRDS, RDS = 22.15% DM) diet, or high RDS (HRDS, RDS = 24.88% DM) diet, respectively. The goats were fed with the experimental diets for 5 weeks. On the last day of the experiment, all goats were anesthetized, and peripheral blood and liver tissue samples were collected. The peripheral blood samples were used in metabolomic analysis and white blood cell (WBC) count, whereas the liver tissue samples were used in transcriptomic analysis. Based on the metabolomics results, the relative abundances of primary bile acids in the peripheral blood were significantly reduced in the group that was fed the HRDS diet (P < 0.05). The WBC count was significantly increased in the HRDS group compared with that in the LRDS and MRDS groups (P < 0.01), indicating that there was inflammation in the HRDS group. Transcriptomic analysis showed that 4 genes related to bile acid secretion (genes: MDR1, RXRα, AE2, SULT2A1) were significantly downregulated in the HRDS group. In addition, genes related to the immune response were upregulated in the HRDS group, suggesting the HRDS diet induced a hepatic inflammatory response mediated by lipopolysaccharides (LPS) (gene: LBP), activated the Toll-like receptor 4 binding (genes: S100A8, S100A9) and the NF-kappa B signaling pathway (genes: LOC106503980, LOC108638497, CD40, LOC102180880, LOC102170970, LOC102175177, LBP, LOC102168903, LOC102185461, LY96 and CXCL8), triggered inflammation and complement responses (genes: C1QB, C1QC, and CFD). The HRDS diet induced a hepatic inflammatory response may be mediated by activating the Toll-like receptor 4 binding and NF-kappa B signaling pathway after free LPS entered the liver. The changes of bile acids profile in blood and the down-regulation of 4 key genes (MDR1, RXRα, AE2, SULT2A1) involved in bile secretion in liver are probably related to liver inflammation.

Microwave ablation for the treatment of peripheral ground-glass nodule-like lung cancer: Long-term results from a multi-center study.

Introduction: Microwave ablation (MWA) is an effective and safe approach for the treatment of ground-glass nodule (GGN)-like lung cancer, but long-term follow-up is warranted. Therefore, this multi-center retrospective study aimed to evaluate the results of MWA for the treatment of peripheral GGN-like lung cancer with a long-term follow-up. Materials and Methods: From June 2013 to January 2018, a total of 87 patients (47 males and 40 females, mean age 64.6 ± 10.2 years) with 87 peripheral lung cancer lesions showing GGN (mean long axis diameter, 17 ± 5 mm) underwent computed tomography (CT)-guided percutaneous MWA. All GGN-like lung cancers were histologically verified. The primary endpoints were local progression-free survival (LPFS) and overall survival (OS). The secondary endpoints were cancer-specific survival (CSS) and complications. Results: During a median follow-up of 65 months, both the 3-year and 5-year LPFS rates were 96.6% and 96.6%. The OS rate was 94.3% at 3 years and 84.9% at 5 years, whereas the 3-year and 5-year CSS rates were 100% and 100%, respectively. No periprocedural deaths were observed. Complications were observed in 49 patients (51.6%). Grade 3 or higher complications included pneumothorax, pleural effusion, hemorrhage, and pulmonary infection, which were identified in ten (10.5%), two (2.1%), two (2.1%), and one (1.1%) patient, respectively. Conclusions: CT-guided percutaneous MWA is an effective, safe, and potentially curative treatment regimen for GGN-like lung cancer.

Experimental confirmation of driving pressure boosting and smoothing for hybrid-drive inertial fusion at the 100-kJ laser facility.

In laser-driven inertial confinement fusion, driving pressure boosting and smoothing are major challenges. A proposed hybrid-drive (HD) scheme can offer such ideal HD pressure performing stable implosion and nonstagnation ignition. Here we report that in the hemispherical and planar ablator targets installed in the semicylindrical hohlraum scaled down from the spherical hohlraum of the designed ignition target, under indirect-drive (ID) laser energies of ~43-50 kJ, the peak radiation temperature of 200 ± 6 eV is achieved. And using only direct-drive (DD) laser energies of 3.6-4.0 kJ at an intensity of 1.8 × 1015 W/cm2, in the hemispherical and planar targets the boosted HD pressures reach 3.8-4.0 and 3.5-3.6 times the radiation ablation pressure respectively. In all the above experiments, significant HD pressure smoothing and the important phenomenon of how a symmetric strong HD shock suppresses the asymmetric ID shock pre-compressed fuel are demonstrated. The backscattering and hot-electron energy fractions both of which are about one-third of that in the DD scheme are also measured.

2,3',4,4',5-Pentachlorobiphenyl induces mitochondria-dependent apoptosis mediated by AhR/Cyp1a1 in mouse germ cells.

Polychlorinated biphenyls (PCBs) are environmental organic pollutants widely used in industry that can bioaccumulate and affect the reproductive systems of male animals of different species. 2,3',4,4',5-Pentachlorobiphenyl (PCB118) is a representative of the 209 toxic PCB congeners. In this study, male mice were exposed to PCB118 at 0, 50, and 500 µg/kg/day for 35 days beginning 3-4 weeks after birth. The results of the study showed that PCB118 exposure during puberty reduced testicular quality, caused tissue damage, decreased sperm motility and sperm count, and increased malformation and testicular cell apoptosis in mice. Moreover, PCB118 increased the oxidative stress levels in sperm and testicular tissue and the expression of aryl hydrocarbon receptor (AhR) and Cyp1a1 and siginificantly decreased the level of nuclear factor-erythroid 2-related factor 2 (Nrf2). The results indicate that PCB118 can activate the AhR/Cyp1a1 pathway and inhibit Nrf2 expression to aggravate testicular oxidative stress and induce cell apoptosis, resulting in testicular and sperm quality damage.

PILN: A posterior information learning network for blind reconstruction of lung CT images.

BACKGROUND AND OBJECTIVE: Computer tomography (CT) imaging technology has played significant roles in the diagnosis and treatment of various lung diseases, but the degradations in CT images usually cause the loss of detailed structural information and interrupt the judgement from clinicians. Therefore, reconstructing noise-free, high-resolution CT images with sharp details from degraded ones is of great importance for the computer-assisted diagnosis (CAD) system. However, current image reconstruction methods suffer from unknown parameters of multiple degradations in actual clinical images. METHODS: To solve these problems, we propose a unified framework, so called Posterior Information Learning Network (PILN), for blind reconstruction of lung CT images. The framework consists of two stages: Firstly, a noise level learning (NLL) network is proposed to quantify the Gaussian and artifact noise degradations into different levels. Inception-residual modules are designed to extract multi-scale deep features from the noisy image, and residual self-attention structures are proposed to refine deep features to essential representations of noise. Secondly, by taking the estimated noise levels as prior information, a cyclic collaborative super-resolution (CyCoSR) network is proposed to iteratively reconstruct the high-resolution CT image and estimate the blur kernel. Two convolutional modules are designed based on cross-attention transformer structure, named as Reconstructor and Parser. The high-resolution image is restored from the degraded image by the Reconstructor under the guidance of the predicted blur kernel, while the blur kernel is estimated by the Parser according to the reconstructed image and the degraded one. The NLL and CyCoSR networks are formulated as an end-to-end framework to handle multiple degradations simultaneously. RESULTS: The proposed PILN is applied to the Cancer Imaging Archive (TCIA) dataset and the Lung Nodule Analysis 2016 Challenge (LUNA16) dataset to evaluate its ability in reconstructing lung CT images. Compared with the state-of-the-art image reconstruction algorithms, it can provide high-resolution images with less noise and sharper details with respect to quantitative benchmarks. CONCLUSIONS: Extensive experimental results demonstrate that our proposed PILN can achieve better performance on blind reconstruction of lung CT images, providing noise-free, detail-sharp and high-resolution images without knowing the parameters of multiple degradation sources.

Facilitating combined biopsy and percutaneous microwave ablation of pulmonary ground-glass opacities using lipiodol localisation.

OBJECTIVES: Whether preoperative localisation is necessary and valuable for the microwave ablation (MWA) of small pulmonary lesions with ground-glass opacity (GGO) remains unclear. This study aimed to explore the role of the Chiba needle and lipiodol localisation techniques in facilitating MWA and biopsy. METHODS: This retrospective before-after study included patients with GGOs who underwent conventional MWA and biopsy treatment in our hospital between January 2018 and December 2019 (group A) or who underwent the Chiba needle and lipiodol localisation treatment before MWA and biopsy between January 2020 and December 2020 (group B). The characteristics of each patient and GGO lesion were collected and analysed to evaluate the safety and effectiveness of the localisation technique. RESULTS: A total of 122 patients with 152 GGOs and 131 patients with 156 GGOs underwent MWA and biopsy in groups A and B, respectively. The primary technique efficacy rate of MWA differed significantly between the two groups (A vs. B: 94.1% vs. 99.4%; p = 0.009). The positive biopsy rate in the two groups was determined by the difference (A vs. B: 93.4% vs. 98.1%; p = 0.042). The incidence of complications did not increase in group B. CONCLUSIONS: Compared with the unmarked group, the Chiba needle and lipiodol localisation technique improved the positive rate of biopsy and the initial effective rate of MWA, without significantly increasing the complication rate. KEY POINTS: • The localisation of the Chiba needle and lipiodol could improve the positive biopsy rate and the initial effective rate of MWA. • The localisation of the Chiba needle and lipiodol does not affect the subsequent MWA and biopsy and does not increase the incidence of pneumothorax and haemorrhage.

Rosmarinic acid potentiates and detoxifies tacrine in combination for Alzheimer's disease.

BACKGROUND: There is no doubt that Alzheimer's disease (AD) is one of the greatest threats facing mankind today. Within the next few decades, Acetylcholinesterase inhibitors (AChEIs) will be the most widely used treatment for Alzheimer's disease. The withdrawal of the first generation AChEIs drug Tacrine (TAC)/ Cognex from the market as a result of hepatotoxicity has always been an interesting case study. Rosmarinic acid (RA) is a natural compound of phenolic acids that has pharmacological activity for inhibiting Alzheimer's disease, as well as liver protection. PURPOSE AND STUDY DESIGN: In this study, we determined that RA can reduce the hepatotoxicity of TAC, and both of them act synergistically to inhibit the progression of AD in mice. METHODS: In addition to the wild type mice (WT) group, the 6-month-old APP/PS1 (APPswe/PSEN1dE9) double-transgenic (Tg) mice were randomly divided into 6 groups: Tg group, TAC group, RA group, TAC+Silymarin (SIL) group, TAC+RA-L (Rosmarinic Acid Low Dose) goup and TAC+RA-H (Rosmarinic Acid High Dose) group. A series of experiments were carried out, including open field test, Morris water maze test, Hematoxylin - Eosin (HE) staining, Nissl staining, biochemical analysis, immunofluorescence analysis, western blotting analysis and so on. RESULTS: RA combined with TAC could enter the brain tissue of AD mice, and the combination of drugs could better improve the cognitive behavior and brain pathological damage of AD mice, reduce the expression of A ß oligomer, inhibit the deposition of A ß, inhibit the activity of AChE and enhance the level of Ach in hippocampus. Both in vivo and in vitro experiments showed that RA could alleviate the hepatotoxicity or liver injury induced by TAC. The Western blot analysis of the liver of AD mice showed that RA combined with TAC might inhibit the apoptosis of Bcl-2/Bax, reduce the programmed apoptosis mediated by caspase-3 and reduce the burden of liver induced by TAC, could inhibit the development of liver apoptosis by alleviating the hepatotoxicity of TAC and inhibiting the phosphorylation of JNK. CONCLUSION: The potential drug combination that combines rosmarinic acid with tacrine could reduce tacrine's hepatotoxicity as well as enhance its therapeutic effect on Alzheimer's disease.

Mitochondria-targeted pentacyclic triterpenoid carbon dots for selective cancer cell destruction via inducing autophagy, apoptosis, as well as ferroptosis.

Natural products have been an important database for anti-cancer drug development. However, low water solubility and poor biocompatibility limit the efficacy of natural products. Carbon dots (CDs), as an emerging 0D material, have unique properties in bioimaging, water solubility and biocompatibility. Here, we prepared three pentacyclic triterpenoids (PTs) included glycyrrhetinic acid (GA), ursolic acid (UA) and oleanolic acid (OA), which have anticancer activity but poor water solubility, as raw materials into CDs to improve disadvantages. Our data indicated that the active surface groups of all three CDs were largely preserved and were able to excite green fluorescence. Their carboxyl edges not only exhibited excellent water solubility, but also specifically targeted tumor cell mitochondria due to high sensitivity to ROS-induced damage and high internal oxidative stress. In cancer cells, the PT-CDs induced cell death through three pathways (apoptosis, ferroptosis, and autophagy), which is essentially the same way their raw materials induce death, but the effect was much stronger than raw materials. Notably, functionalized PT-CDs also exhibited extremely low toxicity. In summary, PT-CDs not only have improved water solubility and biocompatibility, but also retain the structure of their raw materials well and exert better efficacy, which provides new ideas for the development of anti-cancer natural product drugs.

Molecular Dynamics Simulation of the Thermomechanical and Tribological Properties of Graphene-Reinforced Natural Rubber Nanocomposites.

The thermomechanical and tribological properties of graphene (GNS)-reinforced NR were investigated using molecular dynamics (MD) simulations. The amorphous molecular dynamics models of two nanocomposites, i.e., natural rubber (pure NR) and graphene/natural rubber (GNS/NR), were established. In addition, the thermodynamic properties of the two materials, before and after the incorporation of graphene into the natural rubber matrix, were investigated through analytical comparison. The results showed that after the graphene was added to the rubber matrix as a reinforcing material, the elastic modulus and shear modulus were increased by 110% and 94.8%, respectively, the tensile property was increased by 178%, the overall thermal conductivity of the composite system was increased by 59%, the glass transition temperature increased from 223 K to 236 K, and the rigidity of the material matrix was significantly improved. The inherent interactions and wear mechanisms of the polymer nanocomposites were discussed at the atomic scale by analyzing the changes in temperature, atomic velocity, relative atomic concentration, and radial distribution functions at the friction interface in the thickness direction.

Cost and effectiveness of microwave ablation versus video-assisted thoracoscopic surgical resection for ground-glass nodule lung adenocarcinoma.

Purpose: To retrospectively evaluate the cost and effectiveness in consecutive patients with ground-glass nodules (GGNs) treated with video-assisted thoracoscopic surgery (VATS; i.e., wedge resection or segmentectomy) or microwave ablation (MWA). Materials and methods: From May 2017 to April 2019, 204 patients who met our study inclusion criteria were treated with VATS (n = 103) and MWA (n = 101). We calculated the rate of 3-year overall survival (OS), local progression-free survival (LPFS), and cancer-specific survival (CSS), as well as the cost during hospitalization and the length of hospital stay. Results: The rates of 3-year OS, LPFS, and CSS were 100%, 98.9%, and 100%, respectively, in the VATS group and 100%, 100% (p = 0.423), and 100%, respectively, in the MWA group. The median cost of VATS vs. MWA was RMB 54,314.36 vs. RMB 21,464.98 (p < 0.001). The length of hospital stay in the VATS vs. MWA group was 10.0 vs. 6.0 d (p < 0.001). Conclusions: MWA had similar rates of 3-year OS, LPFS, and CSS for patients with GGNs and a dramatically lower cost and shorter hospital stay compared with VATS. Based on efficacy and cost, MWA provides an alternative treatment option for patients with GGNs.

Hypophysitis: A rare but noteworthy immune-related adverse event secondary to camrelizumab therapy.

The programmed cell death 1 (PD-1) inhibitor - camrelizumab - is a promising agent for the treatment of several malignancies. Secondary hypophysitis has been reported in patients treated with the other PD-1 inhibitors such as nivolumab and pembrolizumab. However, camrelizumab-related hypophysitis has not yet been described. Herein, we report three cases of hypophysitis secondary to camrelizumab therapy. Case 1 was a 60-year-old male patient with non-small-cell lung carcinoma, who was diagnosed with central adrenal insufficiency associated with hypophysitis after 11 cycles of camrelizumab treatment (200 mg every 2 weeks). Glucocorticoid therapy rapidly improved his symptoms. Case 2 was a 68-year-old male patient with hepatocellular carcinoma who received ten cycles of camrelizumab (200 mg every 2 weeks) plus apatinib (250 mg daily), before the diagnosis of hypophysitis. Steroid therapy was also efficacious. Case 3 was a 69-year-old male patient diagnosed with renal carcinoma. After eight cycles of camrelizumab therapy (200 mg every 2 weeks) combined with oral apatinib (250 mg daily), the patient presented with hypophysitis, which responded well to glucocorticoid therapy. These results suggest a caution for hypophysitis in patients treated with camrelizumab.

Transcriptome analysis reveals chrysanthemum flower discoloration under high-temperature stress.

Temperature is an important environmental factor affecting plant anthocyanin synthesis. High temperatures are associated with decreased anthocyanin pigmentation in chrysanthemum. To reveal the effects of high temperature on anthocyanin biosynthesis in chrysanthemum, ray florets of the heat-sensitive cultivar "Nannong Ziyunying" (ZYY) were subjected to RNA sequencing. A total of 18,286 unigenes were differentially expressed between the control and treatment groups. Functional annotation and enrichment analyses of these unigenes revealed that the heat shock response and flavonoid pathways were significantly enriched, suggesting that the expression of these genes in response to high temperature is associated with the fading of chrysanthemum flower color. In addition, genes related to anthocyanin synthesis and heat shock response were differentially expressed under high-temperature stress. Finally, to further investigate the molecular mechanism of discoloration under high-temperature stress and facilitate the use of marker-assisted breeding for developing novel heat-tolerant cultivars, these results were used to mine candidate genes by analyzing changes in their transcription levels in chrysanthemum.

Temperature Dependence of Rubber Hyper-Elasticity Based on Different Constitutive Models and Their Prediction Ability.

Based on the electronic universal testing machine with a temperature chamber, this paper investigated the temperature and filler effects on the hyper-elastic behavior of reinforced rubbers and revealed the regulation of the stress and strain of the natural rubber and filled rubber with temperature. The experimental results showed that the hyper-elastic behavior of the filled rubber was temperature-dependent in a wide range. Comparing the adaptability of different models to the stress-strain variation with temperature, the Yeoh model was proven to reasonably characterize the experimental data at different temperatures. Based on the Yeoh model, an explicit temperature-dependent constitutive model was developed to describe the stress-strain response of the filled rubber in a relatively large temperature range. The prediction data of this proposed constitutive model fit well with the test data of the mechanical experiments, indicating that the model is suitable to characterize the large deformation behavior of filled rubbers at different temperatures to a certain degree. The proposed model can be used to obtain the material parameters and has been successfully applied to finite element analysis (FEA), suggesting a high application value. Notably, the model has a simple form and can be conveniently applied in related performance tests of actual production or finite element analysis.

MID-UNet: Multi-input directional UNet for COVID-19 lung infection segmentation from CT images.

Coronavirus Disease 2019 (COVID-19) has spread globally since the first case was reported in December 2019, becoming a world-wide existential health crisis with over 90 million total confirmed cases. Segmentation of lung infection from computed tomography (CT) scans via deep learning method has a great potential in assisting the diagnosis and healthcare for COVID-19. However, current deep learning methods for segmenting infection regions from lung CT images suffer from three problems: (1) Low differentiation of semantic features between the COVID-19 infection regions, other pneumonia regions and normal lung tissues; (2) High variation of visual characteristics between different COVID-19 cases or stages; (3) High difficulty in constraining the irregular boundaries of the COVID-19 infection regions. To solve these problems, a multi-input directional UNet (MID-UNet) is proposed to segment COVID-19 infections in lung CT images. For the input part of the network, we firstly propose an image blurry descriptor to reflect the texture characteristic of the infections. Then the original CT image, the image enhanced by the adaptive histogram equalization, the image filtered by the non-local means filter and the blurry feature map are adopted together as the input of the proposed network. For the structure of the network, we propose the directional convolution block (DCB) which consist of 4 directional convolution kernels. DCBs are applied on the short-cut connections to refine the extracted features before they are transferred to the de-convolution parts. Furthermore, we propose a contour loss based on local curvature histogram then combine it with the binary cross entropy (BCE) loss and the intersection over union (IOU) loss for better segmentation boundary constraint. Experimental results on the COVID-19-CT-Seg dataset demonstrate that our proposed MID-UNet provides superior performance over the state-of-the-art methods on segmenting COVID-19 infections from CT images.

Synchronous Microwave Ablation Combined With Cisplatin Intratumoral Chemotherapy for Large Non-Small Cell Lung Cancer.

Background: Microwave ablation (MWA) and intratumoral chemotherapy (ITC) are useful for treating tumors in animal models; however, their clinical use in patients with large non-small cell lung cancer (NSCLC) remains unknown. This retrospective study aimed to evaluate preliminary outcomes of MWA + ITC for large NSCLC. Methods: From November 2015 to April 2020, a total of 44 NSCLC patients with a mean lesion diameter of 6.1 ± 1.5 cm were enrolled and underwent synchronous MWA + ITC procedures. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were progression-free survival (PFS), complications, overall survival (OS), and associated prognostic factors. Results: The median follow-up time was 19.0 months. At the 1-month CT scan, complete tumor ablation was observed in 47.7% of cases. Median LPFS was 12.1 months; 1-, 2-, and 3-year LPFS rates were 51.2%, 27.9%, and 13.6%, respectively. A shorter LPFS was significantly associated with large lesions (HR 1.23, 95% CI 1.02-1.49; p = 0.032). Median PFS was 8.1 months; 1-, 2-, and 3-year PFS rates were 29.5%, 18.2%, and 9.1%, respectively. LPFS was significantly superior to PFS (p = 0.046). Median OS was 18.8 months. The 1-, 2-, 3-, and 5-year OS rates were 65.9%, 43.2%, 26.4%, and 10.0%, respectively. In univariate comparisons, high performance status (PS) score, smoking, and larger lesions were significantly correlated with poor survival. In multivariate analysis, advanced age, higher PS score, higher stage, larger lesion, and prior systematic treatment were independent prognostic factors for shorter OS. Adverse events were well tolerated and all patients recovered after appropriate intervention. Conclusions: MWA + ITC is a safe and effective new modality of local treatment for large NSCLC and can significantly prolong LPFS.

A study of microwave ablation for small cell lung cancer.

Purpose: To reveal the survival and safety of percutaneous microwave ablation (MWA) combined with chemoradiotherapy (CRT) in treating small cell lung cancer (SCLC). Materials and Methods: Clinical data of 48 SCLC patients who underwent MWA were retrospectively collected; survival and incidence of major complications were analyzed. Results: Totally, 48 SCLC patients underwent 51 MWA procedures. The median overall survival (OS) for all SCLC was 27.0 months (95% confidence interval 22.4-31.6 months). The OS of limited-stage (LS-SCLC) was longer than the extensive-stage (ES-SCLC) (median 48.0 months vs. 25.0 months, P = 0.022). The OS of SCLC with tumor diameter ≤3.0 cm was longer than that of tumor diameter >3.0 cm (median 48.0 months vs. 27.0 months, P = 0.041). For LS-SCLC, the 1-, 2-, 3-, and 5-year survival rate was 91.67%, 72.22%, 66.67%, and 61.11%, respectively. For ES-SCLC, the 1-, 2-, and 3-year survival rates were 83.33%, 50.0%, and 8.33%. Major complications included pneumothorax needing tube placement (29.4%), rarely arrhythmia (2.0%), empyema (2.0%), pulmonary fungal infection (2.0%), and shingles (2.0%). Conclusion: For SCLC patients, who received MWA combined with CRT, OS of LS-SCLC and tumor diameter ≤3.0 cm was better than that of the ES-SCLC and tumor diameter >3.0 cm. For inoperable SCLC, MWA was safe.

Targeting adipokines: A new strategy for the treatment of myocardial fibrosis.

Cardiac fibrosis is a pathogenic factor of many cardiovascular diseases (CVD), which seriously affects people's life and health, causing huge economic losses.Therefore, it is very significant to find an effective treatment for myocardial fibrosis. Adipokines are mainly derived from adipose tissue and have an prominent regulatory effect on glucose and lipid metabolism, inflammation, immune response and cardiovascular function. Adipose tissue is composed of a variety of cell types, including adipocytes, endothelial cells, macrophages and smooth muscle cells. Adipokines mainly include adiponectin, leptin, resistin, visfatin and omentin, which are synthesized and secreted by adipocytes. More and more evidence shows that adipokines can regulate the progress of cardiac fibrosis. This scientific review provides new ideas for targeting adipokines in the treatment of myocardial fibrosis and provides strategies for the development of new, safe, and effective pharmacological antagonists against myocardial fibrosis based on adipokines activity.