Evaluation of the efficacy of a modified method of treating the incisions of the single-port video-assisted thoracoscopic surgery using V-Loc™ barbed sutures.

This paper describes a modified method of applying unidirectional barbed sutures to treat the incisions of the single-port video-assisted thoracoscopic surgery (VATS) and discusses its safety and feasibility. This was a retrospective analysis of 108 patients who underwent single-port VATS admitted to the Department of Thoracic Surgery, the China-Japan Union Hospital of Jilin University, from April 2019 to April 2020. The experimental group (65 patients) was given unidirectional barbed sutures (V-Loc™ sutures) to treat the incision, and the control group (43 patients) had a skin stapler to treat the incision. The complications related to the incisions of the two groups were compared. There was no statistically significant difference between the experimental and control groups regarding incisional infection, incisional splitting, fat liquefaction, and incisional resewing. The pleural fluid outflow from the drainage orifice after removal of the chest tube (0 cases in the experimental group and 7 cases in the control group, P = 0.001) was significantly lower in the experimental group than in the control group. The scores of the scars showed that the experimental group was significantly better than the control group. The modified method of treating the incisions of the single-port VATS with V-Loc™ sutures has good efficacy and safety. It reduces the incidence of pleural fluid outflow from the drainage orifice after removal of the chest tube compared with the traditional stapler suture method, and it has superior cosmetic outcomes.

Neoadjuvant ceritinib treatment in ALK-rearranged locally advanced adenosquamous carcinoma: A case report.

Here, we first report a case of neoadjuvant ceritinib for locally advanced lung adenosquamous carcinoma. In this study, a locally advanced adenosquamous carcinoma (ASC) patient with EML4-ALK fusion who achieved a partial response with neoadjuvant ceritinib treatment after a cycle of neoadjuvant chemotherapy did not show significant efficacy. A complete surgical resection was performed with mild adhesions and a small amount of bleeding intraoperatively. The EML4-ALK fusion was detected by targeted next-generation sequencing (NGS) in both pretreatment biopsy and the postoperative tissue specimens with a dramatic decrease in the allele frequency (26.2% [pre]-2.3% [post]). Pathological examination of the postoperative specimens indicated a diagnosis of ASC but the proportions of adenocarcinoma and squamous cell carcinoma cells in the primary lung tumor and metastatic lymph node site were different, suggesting the various responses to ceritinib. Thus, with the case presented here, we provide the clinical evidence for ALK-positive locally advanced ASC patients benefiting from neoadjuvant ceritinib treatment with a tolerable safety profile, whereas further cohort studies of the efficacy and safety of neoadjuvant ceritinib in such patients are needed.

Critical Role of Notch-1 in Mechanistic Target of Rapamycin Hyperactivity and Vascular Inflammation in Patients With Takayasu Arteritis.

OBJECTIVE: Takayasu arteritis (TA) is a major type of large vessel vasculitis characterized by progressive inflammation in vascular layers. In our recent study we identified a central role of mechanistic target of rapamycin (mTOR) hyperactivity in proinflammatory T cell differentiation in TA. This study was undertaken to explore potential mechanisms underpinning T cell-intrinsic mTOR hyperactivity and vascular inflammation in TA, with a focus on Notch-1. METHODS: Notch-1 expression and activity was determined according to Notch-1, activated Notch-1, and HES-1 levels. We detected mTOR activity with intracellular expression of phosphorylated ribosomal protein S6. Differentiation of proinflammatory T cells was analyzed by detecting Th1 and Th17 lineage-determining transcription factors. The function of Notch-1 was evaluated using γ-secretase inhibitor DAPT and gene knockdown using a short hairpin RNA (shRNA) strategy. We performed our translational study using humanized NSG mouse chimeras in which human vasculitis was induced using immune cells from TA patients. RESULTS: CD4+ T cells from TA patients exerted Notch-1high , leading to mTOR hyperactivity and spontaneous maldifferentiation of Th1 cells and Th17 cells. Blockade of Notch-1 using DAPT and Notch-1 shRNA efficiently abrogated mTOR complex 1 (mTORC1) activation and proinflammatory T cell differentiation. Mechanistically, Notch-1 promoted mTOR expression, interacted with mTOR, and was associated with lysosomal localization of mTOR. Accordingly, systemic administration of DAPT and CD4+ T cell-specific gene knockdown of Notch-1 could alleviate vascular inflammation in humanized TA chimeras. CONCLUSION: Expression of Notch-1 is elevated in CD4+ T cells from TA patients, resulting in mTORC1 hyperactivity and proinflammatory T cell differentiation. Targeting Notch-1 is a promising therapeutic strategy for the clinical management of TA.

DNA Methylation-Mediated Low Expression of CFTR Stimulates the Progression of Lung Adenocarcinoma.

In recent years, the mortality rate of lung adenocarcinoma (LUAD) is persistently increasing, which has already caused a huge impact on human living standards. Hence, there is an urgent need to probe the molecular mechanism of LUAD progression, so as to disclose prognostic and diagnostic markers for patients with LUAD. Methylation 450 K data and mRNA expression data of LUAD were obtained via bioinformatics analysis to screen methylation-driven genes. The expression of the target gene was detected through qRT-PCR, while the methylation level was evaluated via methylation-specific PCR (MSP). The impact of the gene on cell proliferation, migration, invasion, apoptosis and cell cycle was measured through CCK-8, wound healing, Transwell invasion assay, and flow cytometry. CFTR was defined by bioinformatics analysis as the target gene for this study. qRT-PCR revealed that CFTR was lowly expressed in LUAD cells. MSP displayed that the CFTR promoter region in LUAD cells was hypermethylated, and demethylation could pronouncedly increase the level of CFTR mRNA in LUAD cells. Cell biological functional experiments exhibited that CFTR hindered cell proliferation, migration, and invasion, fostered cell apoptosis of LUAD, and blocked the cell cycle in G2-M phase. CFTR was hypermethylated in LUAD, which mediated the low expression of CFTR in LUAD to stimulate the progression of LUAD.

Etoposide plus cisplatin chemotherapy improves the efficacy and safety of small cell lung cancer.

BACKGROUND: According to the statistical data of GLOBOCAN in 2020, the incidence of lung cancer ranks third worldwide. Approximately 60%-70% of newly diagnosed patients with small cell lung cancer (SCLC) has already progressed to extensive-stage SCLC (ES-SCLC). SCLC is sensitive to chemotherapy and radiotherapy, but prone to secondary drug resistance. At present, chemotherapy is the mainstay of treatment for ES-SCLC. This study is designed to evaluate the efficacy and safety of etoposide plus platinum in the treatment of SCLC. METHODS: A retrospective analysis was performed on 112 patients with SCLC admitted to the China-Japan Union Hospital of Jilin University from 2016 to 2018. According to treatment methods, the patients were divided into an EL group (etoposide plus lobaplatin, n = 53) and an EP group (etoposide plus cisplatin, n = 59). The short-term efficacy (objective response rates and disease control rates) and 2-year survival rates were observed. The two groups were compared in terms of serum levels of pro-gastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) before and after treatment. The incidence of adverse reactions was also compared. The quality of life (QOL) of patients was compared by measuring the Karnofsky Performance Status (KPS) scale. The risk factors affecting treatment efficacy were analyzed by multivariate Logistics analysis. RESULTS: Patients in the EL group had similar objective response rate (ORR) and disease control rate (DCR) to those in the EP group. The 2-year survival prognosis (median survival time) between the two groups was not significantly different. After treatment, serum levels of ProGRP, NSE, VEGF and MMP-9 in both groups decreased remarkably, with no remarkable differences between the two groups. The EL group had a remarkably lower incidence of adverse reactions than the EP group. In the EP group, the KPS scores after 6 cycles of treatment were remarkably higher than those after 2 cycles of treatment. ProGRP, NSE, VEGF and MMP-9 were independent risk factors affecting the efficacy of patients with SCLC. CONCLUSION: With equivalent efficacy, EP regimen is safer than EL regimen in the treatment of SCLC, which suggests that etoposide plus platinum has better clinical application value for SCLC.

Long Non-Coding RNA GATA6-AS1 Sponges miR-324-5p to Inhibit Lung Cancer Cell Proliferation and Invasion.

BACKGROUND: Long non-coding RNAs (lncRNAs), which are key regulators of gene expression, are involved in lung cancer progression. Although numerous differentially expressed lncRNAs have been reported, merely a limited number of studies have been performed to verify their functions in lung cancer. METHODS: RNA sequencing data were re-analyzed to investigate the GATA6-AS1 expression in lung cancer. RT-qPCR was performed to verify the expression of GATA6-AS1 in collected tissue samples and cell lines. CCK-8 and transwell assays were carried out to evaluate the role of GATA6-AS1 in lung cancer cells. Dual-luciferase reporter assay and bioinformatic analysis were used to explore the miRNA which can be sponged by GATA6-AS1 in lung cancer cells. RESULTS: Currently, we focused on exploring the role and mechanisms of GATA6-AS1 in lung cancer. Expression of GATA6-AS1 was decreased in lung cancer based on the analysis of RNA sequencing dataset, TCGA data and RT-qPCR of clinical tissue samples. Via overexpression of GATA6-AS1, it was revealed that GATA6-AS1 inhibited lung cancer cell proliferation and invasion. Oncogene miR-324-5p was predicted to interact with GATA6-AS1. RT-qPCR and dual-luciferase reporter assay verified the regulation of miR-324-5p by GATG6-AS1 in lung cancer cells. Overexpression of GATA6-AS1 increased the expression of FBXO11 and SP1, two target genes of miR-324-5p. We further showed that miR-324-5p mimic reversed the effect of GATA6-AS1 overexpression in lung cancer cells. CONCLUSION: Overall, our findings demonstrated GATA6-AS1 as a novel tumor suppressor in lung cancer.