Experiments on physical ablation of long bone using microwave ablation:Defining optimal settings using ex- and in-vivo experiments

Background: Improved survival of cancer patients leads to more skeletal metastatic lesions that need local therapies for tumor control and pain relief. Not all tumors are radiosensitive and alternative therapies are direly needed. Microwave ablation (MWA) is a technique for minimally invasive local tumor control by physical ablation. In soft tissue local temperature ablation is more common, but studies on bone tissue are limited. To ensure safe and effective treatment, studies on local tumor ablation in bone are needed.Method: Microwave ablation was performed on sheep bone, for both in- and ex-vivo settings. Both a slow-cooking MWA protocol (gradually increasing wattage in the first two minutes of ablation) and a fast-cooking protocol (no warm-up period) were used. Heat distribution through the bone during ablation was determined by measuring temperature at 10- and 15mm from the ablation probe (= needle). Ablation size after procedure was measured using nitro-BT staining.Results: In-vivo ablations led to up to six times larger halos than ex-vivo with the same settings. Within both ex- and in-vivo experiments, no differences in halo size or temperature were found for different wattage levels (65W vs 80W). Compared to a fast cooking protocol, a two-minute slow cooking protocol led to increased temperatures and larger halos. Temperatures at 10- and 15mm distance from the needle no longer increased after six minutes. Halo sizes kept increasing over time without an evident plateau.Conclusion: Microwave ablation is technically effective for creating cell death in (sheep) long bone. It is recommended to start ablations with a slow-cooking period, gradually increasing the surrounding tissue temperature in two minutes from 40 to 90°C. Ex-vivo results cannot simply be translated to in-vivo.</p

CXCL13/CXCR5 Axis Predicts Poor Prognosis and Promotes Progression Through PI3K/AKT/mTOR Pathway in Clear Cell Renal Cell Carcinoma

The chemokine ligands and their receptors play critical roles in cancer progression and patients outcomes. We found that CXCL13 was significantly upregulated in ccRCC tissues compared with normal tissues in both The Cancer Genome Atlas (TCGA) cohort and a validated cohort of 90 pairs ccRCC tissues. Statistical analysis showed that high CXCL13 expression related to advanced disease stage and poor prognosis in ccRCC. We also revealed that serum CXCL13 levels in ccRCC patients (n = 50) were significantly higher than in healthy controls (n = 40). Receiver operating characteristic (ROC) curve revealed that tissue and serum CXCL13 expression might be a diagnostic biomarker for ccRCC with an area under curve (AUC) of 0.809 and 0.704, respectively. CXCL13 was significantly associated with its receptor, CXCR5, in ccRCC tissues, and ccRCC patients in high CXCL13 high CXCR5 expression group have a worst prognosis. Functional and mechanistic study revealed that CXCL13 promoted the proliferation and migration of ccRCC cells by binding to CXCR5 and activated PI3K/AKT/mTOR signaling pathway. These results suggested that CXCL13/CXCR5 axis played a significant role in ccRCC and might be a therapeutic target and prognostic biomarker

Knockdown of a novel lincRNA AATBC suppresses proliferation and induces apoptosis in bladder cancer

Long intergenic noncoding RNAs (lincRNAs) play important roles in regulating various biological processes in cancer, including proliferation and apoptosis. However, the roles of lincRNAs in bladder cancer remain elusive. In this study, we identified a novel lincRNA, which we termed AATBC. We found that AATBC was overexpressed in bladder cancer patient tissues and positively correlated with tumor grade and pT stage. We also found that inhibition of AATBC resulted in cell proliferation arrest through G1 cell cycle mediated by cyclin D1, CDK4, p18 and phosphorylated Rb. In addition, inhibition of AATBC induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-9 and caspase-3. The investigation for the signaling pathway revealed that the apoptosis following AATBC knockdown was mediated by activation of phosphorylated JNK and suppression of NRF2. Furthermore, JNK inhibitor SP600125 could attenuate the apoptotic effect achieved by AATBC knockdown, confirming the involvement of JNK signaling in the induced apoptosis. Moreover, mouse xenograft model revealed that knockdown of AATBC led to suppress tumorigenesis in vivo. Taken together, our study indicated that AATBC might play a critical role in pro-proliferation and anti-apoptosis in bladder cancer by regulating cell cycle, intrinsic apoptosis signaling, JNK signaling and NRF2. AATBC could be a potential therapeutic target and molecular biomarker for bladder cancer

Long Non-Coding RNA LUCAT1 Promotes Proliferation and Invasion in Clear Cell Renal Cell Carcinoma Through AKT/GSK-3β Signaling Pathway

Background/Aims: Long non-coding RNAs (lncRNAs) have emerged as new regulators and biomarkers in several cancers. However, few lncRNAs have been well characterized in clear cell renal cell carcinoma (ccRCC). Methods: We investigated the lncRNA expression profile by microarray analysis in 5 corresponding ccRCC tissues and adjacent normal tissues. Lung cancer–associated transcript 1 (LUCAT1) expression was examined in 90 paired ccRCC tissues by real-time PCR and validated by The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis was used to examine the prognostic value of LUCAT1 and CXCL2 in ccRCC patients. Loss and gain of function were performed to explore the effect of LUCAT1 on proliferation and invasion in ccRCC cells. Western blotting was performed to evaluate the underlying mechanisms of LUCAT1 in ccRCC progression. Chemokine stimulation assay was performed to investigate possible mechanisms controlling LUCAT1 expression in ccRCC cells. Enzyme-linked immunosorbent assays were performed to determine serum CXCL2 in ccRCC patients and healthy volunteers. Receiver operating characteristic curve analysis was performed to examine the clinical diagnostic value of serum CXCL2 in ccRCC. Results: We found that LUCAT1 was significantly upregulated in both clinical ccRCC tissues (n = 90) and TCGA ccRCC tissues (n = 448) compared with normal tissues. Statistical analysis revealed that the LUCAT1 expression level positively correlated with tumor T stage (P &#x3c; 0.01), M stage (P &#x3c; 0.01), and TNM stage (P &#x3c; 0.01). Overall survival and disease-free survival time were significantly shorter in the high-LUCAT1-expression group than in the low-LUCAT1-expression group (log-rank P &#x3c; 0.01). LUCAT1 knockdown inhibited ccRCC cell proliferation and colony formation, induced cell cycle arrest at G1 phase, and inhibited cell migration and invasion. Overexpression of LUCAT1 promoted proliferation, migration, and invasion of ccRCC cells. Mechanistic investigations showed that LUCAT1 induced cell cycle G1 arrest by regulating the expression of cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma transcriptional corepressor 1. Moreover, LUCAT1 promoted proliferation and invasion in ccRCC cells partly through inducing the phosphorylation of AKT and suppressing the phosphorylation of GSK-3β. We also revealed that chemokine CXCL2, upregulated in ccRCC, induced LUCAT1 expression and might be a diagnostic and prognostic biomarker in ccRCC. Conclusions: LUCAT1 was upregulated in ccRCC tissues and renal cancer cell lines, and significantly correlated with malignant stage and poor prognosis in ccRCC. LUCAT1 promoted proliferation and invasion in ccRCC cells through the AKT/GSK-3β signaling pathway. We also revealed that LUCAT1 overexpression was induced by chemokine CXCL2. These findings indicate that the CXCL2/LUCAT1/AKT/GSK-3β axis is a potential therapeutic target and molecular biomarker for ccRCC

Study on Design Parameters of Girder Bridge Span Structure in City Railway

[Objective] The compiling of TB 10624—2020 Urban (Suburban) Railway Design Code follows most of the content of GB 50157—2013 Subway Design Code and TB 10623—2014 Intercity Railway Design Code. In order to verify the reasonability of the design parameters of girder bridge span structure in TB 10624—2020, such as deflection-span ratio, natural vibration frequency and dynamic factor, further research is needed. [Method] According to the differences in bridge design codes between city railway and other types of railways, the reasonable design limits of deflection-span ratio, natural frequency and dynamic factor of city railway girder bridge span structure are analyzed on the basis of the theoretical calculation of train-bridge coupling dynamic simulation method. [Result & Conclusion] Due to the train load differences, the deflection design limits for girder bridge span structure in city railway should not follow TB 10623—2014 and the design standard that meets the rigidity requirement of city railway itself should be formulated. The natural frequency design limit applicable to the girder bridge span structure of city railway is proposed. The dynamic coefficient of city railway bridge following that of mixed passenger/freight transport railway bridge in TB 10002—2017 Code for Design of Railway Bridges and Culverts is reasonable and has certain safety guarantee

Study of Testing Method for Dynamic Initiation Toughness of Sandstone under Blasting Loading

In this paper, an internal central single-cracked disk (ICSCD) specimen was proposed for the study of dynamic fracture initiation toughness of sandstone under blasting loading. The ICSCD specimen had a diameter of 400 mm sandstone disc with a 60 mm long crack. Blasting tests were conducted by using the ICSCD specimens. The blasting strain-time curve was obtained from the radial strain gauges placed around the blast hole. The fracture initiation time was determined by circumferential strain gauges placed around the crack tip. The stress history on the blast hole of the sandstone specimen was then derived from measured strain curve through the Laplace transform. The numerical solutions were further obtained by the numerical inversion method. A numerical model was established using the finite element software ANSYS. The type I dynamic stress intensity factor curves of sandstone under blasting loading were derived by the mutual interaction integration method. The results showed that (1) the ICSCD specimen can be used to measure dynamic initiation fracture toughness of rocks; (2) the stress on the blast hole wall can be obtained by the Laplace numerical inversion method; (3) the dynamic initiation fracture toughness of the ICSCD sandstone specimen can be calculated by the experimental-numerical method with a maximum error of only 7%

Numerical Study on Crack Propagation by Using Softening Model under Blasting

A mixed failure criterion, which combined the modified maximum principal stress criterion with the damage model of tensile crack softening, was developed to simulate crack propagation of rock under blasting loads. In order to validate the proposed model, a set of blasting models with a crack and a borehole with different incident angles with the crack were established. By using this model, the property of crack propagation was investigated. The linear equation of state (EOS) was used for rock, and the JWL EOS was applied to the explosive. In order to validate the numerical simulation results, experiments by using PMMA (polymethyl methacrylate) with a crack and a borehole were carried out. The charge structure and incident angle of the blasting experimental model were the same as those in the numerical models. The experiment results agree with the numerical simulation results

Does varicocele grade predict the postoperative changes of semen parameters following left inguinal micro-varicocelectomy?

Objective: To evaluate the relationship between preoperative grade and postoperative changes of semen parameters following left inguinal varicocelectomy. Methods: This study included 44 patients undergoing left microsurgical inguinal varicocelectomy. Internal spermatic veins were classified as large (4 mm or more in diameter), medium (2–4 mm), or small (2 mm or less). Changes in sperm activity, morphology and count were estimated perioperatively. The introperative findings and semen parameters were compared between varicocele groups of grades 2 and 3. Results: Both sperm motility and count improved significantly postoperatively (from (31.9 ± 16.3)% to (47.3  ± 15.5)%, from (28.1 ± 28.1) × 106/mL to (52.1 ± 74.2) × 106/mL). In varicoceles with grade 2 and 3, significant differences were found in the number of large veins (0.4 ± 0.6 vs. 1.2 ± 0.7, p < 0.001) and ultrasonographic maximum diameters of spermatic vein in supine and standing positions (2.3 ± 0.4 cm vs. 2.8 ± 0.6 cm, 3.1 ± 0.7 cm vs. 3.9 ± 0.7 cm, p = 0.001 and 0.001 respectively). However no difference of changes in sperm motility and count was detected ((16.3  ±  13.5)% vs. (14.4  ±  12.6)%, (30.5 ± 84.4) × 106/mL vs. (12.9 ± 20.6) × 106/mL respectively, p = 0.65 and 0.40 respectively). Conclusion: Preoperative varicocele grade might not predict postoperative semen changes regardless of possible existence of anatomic and ultrasonographic associations