Search

Nan Guo,1 Peng Qu,2 Hao Li,2 Liuli Liu,2 Hao Jin,3 Renqi Liu,3 Zhen Zhang,3 Xuan Zhang,2 Yingchun Li,4 Xiaobo Lu,2 Yuejiao Zhao1 1Department of Head and Neck Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, People’s Republic of China; 2Department of Toxicology, School of Public Health, China Medical University, Shenyang, People’s Republic of China; 3Jin Zhou Center for Disease Control and Prevention, Jinzhou, People’s Republic of China; 4Department of Central Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, People’s Republic of ChinaCorrespondence: Yuejiao ZhaoDepartment of Head and Neck Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, People’s Republic of ChinaTel +86 24 31916833Email yuejiaozhao@126.comXiaobo LuDepartment of Toxicology, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People’s Republic of ChinaTel +86 24 31939077Email xblu@cmu.edu.cnObjective: To investigate the associations of polymorphisms in the following DNA double-strand break repair (DSBR) genes with papillary thyroid carcinoma (PTC) risk (including RAD51 rs11852786, RAD51B rs963917, BRCA1 rs12516 and rs8176318, BRCA2 rs15869, XRCC4 rs2035990 and XRCC5 rs2440).Materials and Methods: A matched case–control study was implemented to examine associations between PTC risk and the above polymorphisms. Subsequently, we evaluated the effects of the potential PTC susceptibility-related variant rs15869 on BRCA2 mRNA secondary structure and BRCA2 expression through bioinformatics analysis and experiment validation. Additionally, luciferase assay was used to identify whether rs15869 polymorphism can substantially affect the binding of hsa-miR-1178-3p to BRCA2 mRNA. Finally, Pearson correlation analysis was performed to determine the correlation between the expression of hsa-miR-1178-3p and BRCA2 mRNA and protein in thyroid tissues harboring rs15869 different genotypes.Results: BRCA2 rs15869 CC genotype was associated with a higher risk of PTC than its AA genotype. Subsequently, stratified analyses came to the same conclusion in the female or age< 50 population. Furthermore, we confirmed that the A-to-C substitution of rs15869 changed BRCA2 mRNA secondary structure and contributed to a decreased BRCA2 expression. Mechanistically, a significantly decreased luciferase activity verified a greater binding between hsa-miR-1178-3p and rs15869 C allele, but not the A allele, which was evidenced by the significant negative correlation between hsa-miR-1178-3p with BRCA2 mRNA and protein levels in thyroid tissues with AC and CC genotype but not AA genotype at rs15869.Conclusion: BRCA2 rs15869 is characterized as a potential biomarker associated with PTC risk, highlighting the contribution of the hsa-miR-1178-3p via functional exploration.Keywords: papillary thyroid carcinoma, DNA double-strand break repair, BRCA2, rs15869 polymorphism, hsa-miR-1178-3p

Bisphenol A (BPA), a ubiquitous endocrine‐disrupting chemical, alters the function of endocrine system and enhances the susceptibility to tumorigenesis in several hormone‐dependent tumours as thyroid carcinoma. About 50% of papillary thyroid cancers (PTC), the most common type of thyroid malignancy, harbours the BRAF V600E mutation. This study aimed to investigate a potential combined effect of BPA exposure and BRAF V600E mutation on epithelial‐mesenchymal transition (EMT) in PTC. Firstly, the level of BPA in plasma, the evaluation of BRAFV600E mutation and the level of EMT‐related proteins in PTC samples were individually determined. Additionally, the migration, invasion, colony formation capacity and the expression of EMT‐related proteins after exposure to BPA were precisely analysed in vitro thyroid cells genetically modified by the introduction of BRAF V600E mutation. Moreover, ERK‐Cox2 signalling pathway was also introduced to explore the possible mechanism in PTC development. As expected, whether the clinical investigation or cultured thyroid cells demonstrated that BPA at a concentration compatible with human exposed levels (10‐7 M) synergized with the BRAF V600E mutation promoted EMT via the activation of ERK‐Cox2 signalling pathway. Our findings offer some evidence that BPA as an environmental risk factor can facilitate the progression of PTC harbouring BRAF V600E mutation.

Background/Aim. Pericapsular nerve group block (PNGB) does not affect the motor nerve while blocking obturator and femoral nerves. The aim of study was to determine the application value of PNGB for elderly hip replacement. Methods. Ninety elderly patients undergoing hip replacement from March 2019 to October 2020 were randomly divided into fascia iliaca compartment block (FICB) and PNGB groups. FICB and PNGB were performed prior to subarachnoid block (SAB), respectively. Their baseline data, operation conditions, incidence of adverse reactions, visual analogue scale (VAS) score, heart rate (HR), mean arterial pressure (MAP), plasma cortisol (COR) and epinephrine (E) were compared. Results. VAS score, E and COR levels in PNGB group were lower than those in FICB group at time points T2-T4 (T2: 10 min after nerve block; T3: at position changing; T4: after position changing) (p0.05). In PNGB group, the ultrasonic imaging time was shorter, the time point of pressing patient-controlled analgesia (PCA) for the first time was later, and the numbers of pressing PCA were fewer than those of FICB group (p

Bisphenol A (BPA) and di-(2-ethylhcxyl) phthalate (DEHP) are exist widespread in the environment and produce adverse effect to human as environmental disruptors (EDCs). Epidemiological studies have found that the exposure of DEHP and BPA could increase the susceptibility to thyroid diseases including thyroid cancer and benign thyroid nodules. Due to the existence of multiple pollutants in our daily life, the mixed toxic effects of exposure and their interrelationships may distinguish from the exposure to a single chemical, so it is of great significance to explore the mixed toxic effect of DEHP and BPA co-exposure. Thyroid, as one of the target organs of EDCs, is prone to tumor occurrence, however, whether the mixture of BPA and DEHP will affect the occurrence of thyroid cancer is still obscure. We aim to investigate the effect of single or combined exposure to BPA and DEHP on the occurrence of thyroid cancer. An animal model of exposure to BPA and DEHP was firstly established to evaluate their effect on DMD-induced thyroid cancer. Additionally, human thyroid cancer cells BCPAP and thyroid cells Nthy-ori3-1 were used to further clarify some possible mechanisms of BPA and MEHP, the main metabolite of DEHP. Consequently, we found that BPA alone could increase the incidence of thyroid tumors in female rats compared with DEHP, and DEHP enhanced the effect of BPA on cancer promotion. BPA alone and in combination with DEHP mainly induced the expression of HDAC6, inhibited tumor suppressor gene PTEN upregulated the expression of oncogene c-MYC, and eventually elevate the susceptibility to thyroid tumors. Mechanistically, BPA alone and in combination with MEHP could significantly induce the proliferation of BCPAP cells depending on HDAC6, which could modulate H3K9ac to inhibit PTEN, activate AKT signaling pathway, and simultaneously upregulate the expression of c-MYC. Interestingly, we found that BPA alone and in combination with MEHP could significantly induce the proliferation of Nthy-ori3-1 cells independent on HDAC6 via activating ERK signaling pathway. Taken together, these findings not only provide new evidence of the promoting effect of BPA and DEHP on thyroid cancer but also discusses some possible mechanisms underlying these effects.

We demonstrate two type phasing methods for tiled-aperture coherent beam combining for high-power lasers based on the near and far field measurement techniques respectively, a comparison is made.

A deep convolutional neural network is employed to simultaneously measure the beam-pointing and phase difference of sub-beams from a single far-field interference fringe for coherent beam combining systems. The amplitudes of sub-beams in the measurement path are modulated in order to prevent measuring mistakes caused by the symmetry of beam-pointing. This method is able to measure beam-pointing and phase difference with an RMS accuracy of about 0.2 μrad and λ/250, respectively, in a two-beam coherent beam combining system.

In this Letter, we report the demonstration of the coherent beam combining (CBC) of two-beam femtosecond laser pulses based on chirped-pulse amplification (CPA). To the best of our knowledge, this is the first experimental realization of coherent combination pulses from Ti:sapphire CPA systems. In this experiment, the combined laser beams operate at a repetition rate of 1 Hz, and a reference laser is introduced to detect the phase error between the sub-beams. Finally, we realize a coherent combining efficiency of 90% which verified the feasibility for CPA CBC. Moreover, the influence of the amplification process on CBC is studied.

We proposed a new phase-locking technique for multibeam coherent beam combination. By near-field angle modulation and angular spectrum measurement, we obtained the relative phase between each pair of beams with one camera. This method is appropriate for multibeam schemes and possesses the advantages of high accuracy, resistance to energy fluctuation, and simplicity, as shown by the analysis in this study. In a proof-of-principle experiment, we realized the phase-locking of three beams, achieving a Strehl ratio of 89.5%. Our method may supply a scheme for multibeam coherent combining of ultra-intense bulk laser systems.