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AnteayerPLOS ONE Medicine&Health

Automated VMAT planning for short-course radiotherapy in locally advanced rectal cancer

by Qiong Zhou, Liwen Qian, Chong Shen, Xinyan Bei, Gaojie Liu, Xiaonan Sun

Purpose

This study aims to develop a fully automated VMAT planning program for short-course radiotherapy (SCRT) in Locally Advanced Rectal Cancer (LARC) and assess its plan quality, feasibility, and efficiency.

Materials and methods

Thirty LARC patients who underwent short-course VMAT treatment were retrospectively selected from our institution for this study. An auto-planning program for neoadjuvant short-course radiotherapy (SCRT) in LARC was developed using the RayStation scripting platform integrated with the Python environment. The patients were re-planned using this auto-planning program. Subsequently, the differences between the automatic plans (APs) and existing manual plans (MPs) were compared in terms of plan quality, monitor units (MU), plan complexity, and other dosimetric parameters. Plan quality assurance (QA) was performed using the ArcCHECK dosimetric verification system.

Results

Compared to MPs, the APs achieved similar target coverage and conformity, while providing more rapid dose fall-off. Except for the V5Gy dose level, other dosimetric metrics (V25 Gy, V23 Gy, V15 Gy, Dmean, etc.) for the small bowel were significantly lower in the AP compared to the MP (p  Conclusion

We developed a fully automated, feasible SCRT VMAT planning program for LARC. This program significantly enhanced plan quality and efficiency while substantially reducing the dose to OARs.

Association between hyperlipidemia and nephrolithiasis: A comprehensive bioinformatics analysis deciphering the potential common denominator pathogenesis

by Zhikai Su, Zhenjie Ling, Haoqiang Chen, Lei Hu, Songtao Xiang, Qian Li, Jianfu Zhou

Objective

Evidence suggests that nephrolithiasis and hyperlipidemia are linked. The study is designed to identify diagnostic biomarkers for nephrolithiasis in conjunction with hyperlipidemia using bioinformatics analysis, while exploring the potential common denominator pathogenesis.

Methods

The NCBI Gene Expression Omnibus (GEO) database provided separate datasets for nephrolithiasis and hyperlipidemia. We employed the R limma package to detect differentially expressed genes (DEGs), which were subsequently analyzed for enrichment using Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Immune cell infiltration was analyzed by the CIBERSORT method. The WGCNA-R package clustered genes with similar expression profiles, followed by an analysis of the associations between the modules and specific traits or phenotypes. The STRING database was utilized to establish a protein-protein interaction (PPI) network and key functional modules, which were then analyzed using Cytoscape software. Diagnostic genes for both diseases were screened from core hub genes using least absolute shrinkage and selection operator (Lasso) regression. Subsequently, we generated receiver operating characteristic (ROC) curves to validate the predictive ability of these diagnostic genes for diagnosing nephrolithiasis in combination with hyperlipidemia. Lastly, the Network Analyst platform facilitated the construction of transcription factor-gene (TF-gene) and TF-miRNA regulatory networks.

Results

Based on datasets of nephrolithiasis and hyperlipidemia, we identified 167 DEGs and 74 hub genes through WGCNA. Using PPI networks and machine learning techniques, we recognized three frequently diagnostic genes (HSP90AB1, HSPA5, and STUB1), which demonstrated high diagnostic validity. The functional enrichment of these three diagnostic genes primarily involved pathways related to cellular metabolism.

Conclusions

Our study identified three candidate diagnostic genes that can predict nephrolithiasis in conjunction with hyperlipidemia, providing a solid foundation for further exploration into the pathogenesis of nephrolithiasis and hyperlipidemia.

The dysregulation of PARP9 expression is linked to apoptosis and DNA damage in gastric cancer cells

by Yating Li, Xing Wang, Xiaolong Liu, Xiangjie Li, Jianling Zhang, Yulan Li

Background

Gastric cancer (GC) is a highly malignant gastrointestinal tumor characterized by difficult early diagnosis and poor prognosis. Therefore, it is imperative to explore potential therapeutic targets for gastric cancer. PARP9 is abnormally expressed in a variety of tumors and is associated with tumor cell apoptosis and DNA damage. However, its relationship with GC has not been fully studied.

Methods

The expression and prognostic significance of PARP9 in gastric cancer (GC) were examined using bioinformatics approaches. Cell lines with either knockdown or overexpression of PARP9 were established through lentiviral transduction, and the role of PARP9 in the malignant phenotypes of GC cells was validated via CCK8 assays, wound healing assays, clonogenic assays, and Transwell migration experiments. Finally, alterations in downstream targets and signaling pathways following changes in PARP9 expression were analyzed through RNA sequencing.

Results

PARP9 is highly expressed in GC tissues and is associated with poor prognosis. PARP9 knockdown can significantly inhibit the proliferation, invasion and migration of GC cells, and increase the apoptosis and DNA damage of GC cells. The therapeutic process of PARP9 in GC may be realized by synergistic interaction with SOX6 through MAPK signaling pathway.

Conclusions

Our study reveals a potential link between PARP9 and GC, providing a new target for the treatment of GC.

Obesity-induced activation of NADPH oxidase 2 prolongs cardiac repolarization via inhibiting K<sup>+</sup> currents

by Bin Li, Yating Chen, Maoxiang Zhao, Zhijie Chen, Zhuhui Lin, Jie Liu, Xueping Wang, Jiancheng Zhang, Yang Li

Obesity is associated with abnormal repolarization manifested by QT interval prolongation, and oxidative stress is an important link between obesity and arrhythmias. However, the underlying electrophysiological and molecular mechanisms remain unclear. The aim of this study is to evaluate the role of obesity in potassium current in ventricular myocytes and the potential mechanism of NADPH oxidase 2 (Nox2). We investigated the effect of Nox2 on cardiac repolarization without compromising its expression and function in other systems using mice with conditional cardiac-specific deletions of Nox2 (knockout [KO]). Wild-type, KO, and Flox littermate mice were randomized to either the control or high-fat diet (HFD) groups. Surface electrocardiograms were recorded to analyze repolarization in vivo. Whole-cell patch-clamp techniques were used to evaluate the electrophysiological phenotype of isolated myocytes in vitro. Western blotting was performed to assess protein expression levels. Compared with the control mice, the HFD group had a prolonged QTc. The consequences of an HFD were not attributed to delayed rectifier K+ and inward-rectifier K+ currents but were associated with reduced peak outward KV and fast transient outward K+ currents. Downregulated expression of KV4.2 and KChIP2, comprising functional Ito channel pore-forming (α) and accessory (β) subunits, was detected in HFD mice. Nox2-KO reversed the effect of obesity on Ipeak and Ito amplitude. Our data demonstrate that obesity mediates impaired cardiac repolarization in mice, manifested by QTc at the whole organism level and action potential duration at the cellular level, and correlated with Nox2. The electrophysiological and molecular aspects of this phenomenon were mediated by repolarizing outward K+ currents.

Effects of immersion bathing in <i>Lactobacillus plantarum</i> CLY-05 on the growth performance, non-specific immune enzyme activities and gut microbiota of <i>Apostichopus japonicus</i>

by Bin Li, Jinjin Wang, Jianlong Ge, Meijie Liao, Xiaojun Rong, Jinyan Wang, Yingeng Wang, Zheng Zhang, Chunyuan Wang, Yongxiang Yu

In order to study the optimal use of Lactobacillus plantarum in sea cucumber (Apostichopus japonicus), 49 days feeding trial was conducted to determine the influence of immersion bathing in different concentrations of Lactobacillus plantarum CLY-05 on body weight gain rate and non-specific immune activities. The potential effect of CLY-05 on gut microbiota was also analyzed during the immersion bathing at the optimum concentration. The results showed that the body weight growth rate of all bathing groups was higher than that of control. The highest specific growth rate (4.58%) and weight gain rate (25.35%) was achieved at the bacterial concentration of 1×103 CFU/mL. The activities of non-specific immune enzymes (ACP, AKP, SOD and LZM) of all bathing groups increased after immersion bathing, and the enzyme activities of groups bathed with the bacterium at 1×103 and 1×104 CFU/mL reached the highest. Therefore, 1×103 CFU/mL was considered as the optimum concentration of L. plantarum CLY-05 for A. japonicus pond culture. The results of gut microbiota analysis showed that the gut microbiota changed with the addition of L. plantarum CLY-05, and the richness and diversity of the gut microbiota peaked on day 14 and day 21, respectively. The correlation analysis revealed that the non-specific immune enzyme activities were significantly correlated to some gut bacteria (in the phyla Proteobacteria, Firmicutes) after immersion bathing in L. plantarum CLY-05. These findings provide the theoretical foundation for probiotic application in sea cucumber farming.

Construction of reusable fluorescent assembled 3D-printed hydrogen-based models to simulate minimally invasive resection of complex liver cancer

by Wenli Cao, Xiaofeng Pan, Liming Jin, Jie Liu, Jie Cao, Lei Jin, Fangqiang Wei

Complex liver cancer is often difficult to expose or dissect, and the surgery is often challenging. 3D-printed models may realistically present 3D anatomical structure, which has certain value in planning and training of liver surgery. However, the existing 3D-printed models are all monolithic models, which are difficult to reuse and limited in clinical application. It is also rare to carry fluorescence to accurately present tumor lesions. Here we report reusable fluorescent assembled 3D-printed models to mimic minimally invasive resection of complex liver cancer. Based on the models, multiple copies of liver lesion structure assembled accessories can be printed for the same patient or different patients, ensuring the quantity and quality of simulated surgical training, and greatly reducing the cost of simulated surgical training. The addition of fluorescence is helpful in accurately presenting tumor lesions. The reusable fluorescent assembled 3D-printed models may mimic minimally invasive resection of complex liver cancer, demonstrating potential value in simulated surgery.

Microdissection testicular sperm extraction outcomes in azoospermic patients post-orchidopexy surgery: A systematic review and meta-analysis

by Hao-nan He, Hong Xiao, Rui-jie Yao, Shi-jie Liao, Jun-hang Zheng, Hui-liang Zhou

Cryptorchidism is a common cause of male infertility, often necessitating microdissection testicular sperm extraction (m-TESE) for sperm retrieval post-surgery. However, uncertainties persist regarding m-TESE outcomes and influencing factors following cryptorchidism surgery. A systematic review and meta-analysis were conducted to evaluate sperm retrieval rates (SRR) among patients undergoing m-TESE after cryptorchidism surgery. Factors including age at orchidopexy, age at m-TESE, type of cryptorchidism, serum hormone levels, testicular volume, and interval from surgery to m-TESE were analyzed for their impact on SRR.Nine studies encompassing 935 patients were included. The overall SRR was 57% (95% confidence interval [CI] 51% to 63%). Compared to patients with negative sperm retrieval (SR-), patients with positive sperm retrieval (SR+) underwent m-TESE at an older age (1.81 years; 95% CI 1.17 to 2.45) and orchidopexy at a younger age (-3.35 years; 95% CI -6.34 to -0.36). Different types of cryptorchidism (including high scrotal, inguinal canal, intra-abdominal) significantly influenced SRR (P0.05). Furthermore, SR- patients typically experienced shorter intervals from orchidopexy to m-TESE compared to SR+ patients (34.09 months; 95% CI 0.40 to 67.77). Earlier orchidopexy and much later m-TESE procedures, as well as undescended testis closer to the scrotum, increase the likelihood of successful sperm retrieval. Orchidopexy for cryptorchidism should be done as early as possible, whether it is performed before 18 months of age or detected at a much older age. In patients with undetected cryptorchidism and azoospermia after puberty, m-TESE should not be performed immediately after orchidopexy, the optimal interval from orchidopexy to m-TESE still requires further study.

High-intensity focused ultrasound ablation combined with immunotherapy for treating liver metastases: A prospective non-randomized trial

by Xiyue Yang, Yao Liao, Lingli Fan, Binwei Lin, Jie Li, Danfeng Wu, Dongbiao Liao, Li Yuan, Jihui Liu, Feng Gao, Gang Feng, Xiaobo Du

Purpose

Given the unique features of the liver, it is necessary to combine immunotherapy with other therapies to improve its efficacy in patients of advanced cancer with liver metastases (LM). High-intensity focused ultrasound (HIFU) ablation is now widely used in clinical practice and can enhanced immune benefits. The study is intended to prospectively evaluate the safety and clinical feasibility of HIFU ablation in combination with systemic immunotherapy for patients with liver metastases.

Methods

The study enrolled 14 patients with LM who received ultrasound-guided HIFU ablation combined with immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein 1 (anti-PD-1 agents manufactured in China) at Mianyang Central Hospital. Patients were followed up for adverse events (AEs) during the trial, using the CommonTerminology Criteria for Adverse Events v5.0(CTCAE v5.0) as the standard. Tumour response after treatment was assessed using computerized tomography.

Results

The 14 patients (age range, 35–84 years) underwent HIFU ablation at 19 metastatic sites and systemic immunotherapy. The mean lesion volume was 179.9 cm3 (maximum: 733.1 cm3). Median follow-up for this trial was 9 months (range: 3–21) months. The study is clinically feasible and acceptable to patients.

Conclusion

This prospective study confirmed that HIFU combined with immunotherapy is clinically feasible and safe for treating liver metastases.

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