Venous thromboembolism (VTE) as the most common cancer-associated complication has become the second death-causing reason among cancer patients. The management of VTE in patients with lung adenocarcinoma should focus on early and timely detection of risk factors. The aim of the study is to investigate the current situation of VTE in patients with lung adenocarcinoma treated with anti-tumor therapy and then explore the risk factors associated with the occurrence of VTE during anti-tumor therapy for early detection and screening of VTE.The present study included patients diagnosed as lung adenocarcinoma undergoing anti-tumor therapy in First Affiliated Hospital of Nanjing Medical University between December 2019 and May 2021. The risk factors were identified via univariate and multivariate Cox analysis. The incidence of independent risk factors were investigated through Kaplan-Meier curves combined with Log-rank test.The results of univariate and multivariate Cox regression showed that history of VTE, targeted therapy and radiotherapy were risk factors for VTE in patients with lung adenocarcinoma treated with anti-tumor therapy (P<0.05). Furthermore, the results of Kaplan-Meier curves and Log-rank tests indicated the incidences of VTE in patients with history of VTE, targeted therapy and radiotherapy were higher (P<0.05).History of VTE, radiotherapy and targeted therapy are found as independent risk factors for the occurrence of VTE, which should be identified and monitored for reduction of VTE incidence. .【中文题目：抗肿瘤治疗的肺腺癌患者发生静脉血栓栓塞的情况及危险因素分析】 【中文摘要：背景与目的 静脉血栓栓塞（venous thromboembolism, VTE）是癌症患者最常见的并发症，也是癌症患者死亡的第二大原因。肺腺癌患者发生VTE的管理重点在于早期、及时发现危险因素。本研究旨在调查抗肿瘤治疗的肺腺癌患者VTE发生现状，探讨在抗肿瘤治疗过程中发生VTE的影响因素，为VTE的早期识别和筛查提供依据。方法 收集2019年12月-2021年5月于南京医科大学第一附属医院确诊为肺腺癌且行抗肿瘤治疗患者的临床资料，分别采用Cox单因素及多因素回归分析、Kaplan-Meier曲线和Log-rank检验比较独立危险因素影响VTE发生的差异。结果 Cox回归单因素及多因素分析显示，VTE病史、靶向药物治疗、放疗是抗肿瘤治疗肺腺癌患者VTE发生的危险因素（P<0.05）。Kaplan-Meier曲线和Log-rank检验比较独立危险因素发现VTE病史、靶向治疗、放疗患者的VTE发生率更高（P<0.05）。结论 有VTE病史、放疗、靶向治疗是VTE发生的高危因素，对于这类影响因素的早期识别和筛查有助于今后临床实践中VTE的防控和管理。 】 【中文关键词：肺肿瘤；静脉血栓栓塞；抗肿瘤治疗；影响因素】.
Abstract The 70-kD heat shock proteins (Hsp70s) are highly conserved molecular chaperones that play essential roles in cellular processes including abiotic stress responses. Physcomitrella patens serves as a representative of the first terrestrial plants and can recover from serious dehydration. To assess the possible relationship between P. patens Hsp70s and dehydration tolerance, we analyzed the P. patens genome and found at least 21 genes encoding Hsp70s. Gene structure and motif composition were relatively conserved in each subfamily. The intron-exon structure of PpcpHsp70-2 was different from that of other PpcpHsp70s ; this gene exhibits several forms of intron retention, indicating that introns may play important roles in regulating gene expression. We observed expansion of Hsp70s in P. patens , which may reflect adaptations related to development and dehydration tolerance and results mainly from tandem and segmental duplications. Expression profiles of rice, Arabidopsis and P. patens Hsp70 genes revealed that more than half of the Hsp70 genes were responsive to ABA, salt and drought. The presence of overrepresented cis -elements (DOFCOREZM and GCCCORE) among stress-responsive Hsp70s suggests that they share a common regulatory pathway. Moss plants overexpressing PpcpHsp70-2 showed salt and dehydration tolerance, further supporting a role in adaptation to land. This work highlights directions for future functional analyses of Hsp70s.
Patent foramen ovale (PFO) is a congenital defect between the atria, resulting in abnormal hemodynamics. We conducted a genome-wide association study (GWAS) to identify common genetic variants associated with PFO. We performed a whole genome sequencing in a discovery cohort of 3,227 unrelated Chinese participants screened for PFO via contrast transthoracic echocardiography (cTTE). Single-nucleotide polymorphisms (SNPs) associated with PFO were further validated by Sanger sequencing and subsequently were evaluated in a validation cohort. Expression quantitative trait loci (eQTL) analysis was conducted using the GTEx database. Single-cell sequencing analyses with pseudotime trajectory modeling were employed to evaluate their expression in human fetal hearts. The case-control GWAS of discovery cohort ultimately included 517 cases and 517 demographically matched controls. Of the 7,040,407 variants assessed, we identified rs1227675732 (OR = 2.903; 95% CI, 1.961 to 4.297; p = 3.05 × 10-8), rs62206790 (OR = 2.780; 95% CI, 1.864 to 4.146; p = 2.02 × 10-7), rs879176184 (OR = 2.724; 95% CI, 1.822 to 4.073; p = 4.30 × 10-7) and rs13115019 (OR = 2.437; 95% CI, 1.702 to 3.488; p = 5.80 × 10-7) as high-risk variants for PFO, while rs57922961 (OR = 0.5081; 95% CI, 0.388 to 0.666; p = 6.82 × 10-7) was identified as protective variant. These variations were replicated in the validation cohort (111 cases and 152 controls). Single-cell sequencing showed that CNOT2, KCNMB4, MLLT10, IGBP1, and FRG1 were highly expressed with significant changes during heart development. The identification of susceptible loci for PFO might provide insights into the pathogenesis of PFO and contribute to understanding heart development. https://www.chictr.org.cn/showproj.html?proj=40590, identifier ChiCTR1900024623.
Abstract CRISPR/Cas9 is a valuable tool for both basic and applied research that has been widely applied to different plant species. Nonetheless, a systematical assessment of the efficiency of this method is not available for the allotetraploid Brassica napus —an important oilseed crop. In this study, we examined the mutation efficiency of the CRISPR/Cas9 method for 12 genes and also determined the pattern, specificity and heritability of these gene modifications in B . napus . The average mutation frequency for a single-gene targeted sgRNA in the T0 generation is 65.3%. For paralogous genes located in conserved regions that were targeted by sgRNAs, we observed mutation frequencies that ranged from 27.6% to 96.6%. Homozygotes were readily found in T0 plants. A total of 48.2% of the gene mutations, including homozygotes, bi-alleles, and heterozygotes were stably inherited as classic Mendelian alleles in the next generation (T1) without any new mutations or reversions. Moreover, no mutation was found in the putative off-target sites among the examined T0 plants. Collectively, our results demonstrate that CRISPR/Cas9 is an efficient tool for creating targeted genome modifications at multiple loci that are stable and inheritable in B . napus . These findings open many doors for biotechnological applications in oilseed crops.
Abstract Glial scar formation is a major obstacle to nerve regeneration following spinal cord injury (SCI). Pin1 and the PI3K/AKT/CDK2 signaling pathway play crucial roles in neuronal regulation, but research on their involvement in glial scarring remains limited. In this study, we have for the first time observed that Pin1, PI3K, AKT, and CDK2 are upregulated and interact with each other following SCI. Further experiments revealed that Pin1 contributes to the development of glial scars by promoting astrocyte proliferation, inhibiting apoptosis, and activating the PI3K/AKT/CDK2 pathway. Additionally, all‐trans retinoic acid (ATRA), a specific chemical inhibitor of Pin1, effectively suppresses Pin1 expression. However, its clinical application is limited by its short half‐life and susceptibility to inactivation. To address these issues, we have developed a thermosensitive sodium beta‐glycerophosphate (β‐GP)/chitosan (CS) hydrogel loaded with ATRA (β‐GP/CS@ATRA). This hydrogel exhibits favorable morphology and biocompatibility. Compared to free ATRA, the β‐GP/CS@ATRA hydrogel significantly enhances functional motor recovery after SCI and protects spinal cord tissue, thereby inhibiting glial scar formation. Mechanistically, ATRA administration blocks the development of glial scars and the activation of the PI3K/AKT/CDK2 pathway by inhibiting Pin1 expression. This study suggests that combining ATRA with a hydrogel to target Pin1 expression may be a promising strategy for treating glial scar formation following SCI.
Liquid filled double bottom structure is a usual type for large surface vessel, so the optimal design of which has important significance for viability of vessels in war. Appling a FEM process of MSC.Dytan, and changing the depth of liquid cabins, the thickness of bottoms and the thickness of stiffening, the response of different double bottom structures to underwater explosion were studied. After comparing and analyzing the deformation, the optimal design method of double bottom structures filled with liquid resisting underwater explosion was achieved. The best depth of water in water cabins is 90%, the best ratio of thickness of inner bottom and outer bottom is 11/9, and the stiffening should be thicker than outer bottom and thinner than inner bottom.
An analytical model is developed for high-velocity perforation of moderately thick, plain-woven laminated plates by deformable blunt projectiles. Based on different mechanical states and energy-dissipative mechanisms, penetration is divided into three consecutive stages: cratering and mushrooming, shearing and compression, and stretching deformation. The model is based on the concept of energy conservation, which allows approximative calculation of residual velocity, and hence, ballistic limit. The model is validated by using experimental results for ultra-high molecular weight polyethylene-woven laminated plates in terms of residual velocity and ballistic limit. The model considers the mushrooming deformation of projectiles. Consequently, as projectile velocity increases, the accuracy and universality of the model improve.
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