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In non-small cell lung cancer(NSCLC),the heterogeneity promotes drug resistance,and the restricted expression of programmed death-ligand 1(PD-L1)limits the immunotherapy benefits.Based on the mechanisms related to translation regulation and the association with PD-L1 of methyltransferase-like 3(METTL3),the novel small-molecule inhibitor STM2457 is assumed to be useful for the treat-ment of NSCLC.We evaluated the efficacy of STM2457 in vivo and in vitro and confirmed the effects of its inhibition on disease progression.Next,we explored the effect of STM2457 on METTL3 and revealed its effects on the inhibition of catalytic activity and upregulation of METTL3 protein expression.Importantly,we described the genome-wide characteristics of multiple omics data ac-quired from RNA sequencing,ribosome profiling,and methylated RNA immunoprecipitation sequencing data under STM2457 treatment or METTL3 knockout.We also constructed a model for the regulation of the translation of METTL3 and PD-L1.Finally,we found PD-Ll upregulation by STM2457 in vivo and in vitro.In conclusion,STM2457 is a potential novel suppressor based on its inhibitory effect on tumor progression and may be able to overcome the heterogeneity based on its impact on the translatome.Furthermore,it can improve the immunotherapy outcomes based on PD-L1 upregulation in NSCLC.
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BACKGROUND@#Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE).@*METHODS@#This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE.@*RESULTS@#This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively.@*CONCLUSIONS@#Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.
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Objective@#To compare the effects of video assisted thoracoscopic surgery(VATS) of intercostal surgery and by subxiphoid surgical treatment for early thymoma, to investigate the feasibility and clinical application value of VATS subxiphoid surgical treatment for thymoma.@*Methods@#From January 2014 to January 2017, 30 thymoma patients who met the diagnostic criteria of the Masaoka stageⅠ~Ⅱ in the People's Hospital of Jingshan County were selected, and were divided into two groups according to the different surgical methods.The observation group (12 patients) received VATS underwent subxiphoid surgery, 18 patients in the control group were treated with VATS intercostal surgery.The operation time, blood loss, drainage time, length of stay, degree of pain, antibacterial time, incidence rate of complication and patients' satisfaction were compared between the two groups.@*Results@#The preoperative general data between the two groups had no statistically significant differences(all P>0.05). The operation time, intraoperative bleeding volume, postoperative drainage time, antibacterial time, postoperative hospitalization time in the observation group were (102.2±26.6)min, (105.9±29.4)mL, (3.8±1.4)d, (6.8±0.3)d, (8.5±1.6)d, respectively, which in the control group were (124.6±35.1)min, (255.6±82.8)mL, (5.2±1.2)d, (9.3±0.8)d, (14.4±1.8)d, respectively, there were statistically significant differences between the two groups(t=1.516, 2.517, 2.857, 4.462, 3.327, all P<0.05). The incidence rate of complications (8.33% vs.16.67%), satisfaction(82% vs.59%) between the two groups had statistically significant differences(χ2=4.013, 4.427, all P<0.05). During the follow-up period, there was no recurrence or metastasis in the two groups.@*Conclusion@#Compared with VATS intercostal surgery, VATS subxiphoid approach for surgical treatment of thymoma can reduce surgical trauma and reduce the incidence of complications, reduce the pain of patients, shorten the hospitalization time, its curative effect is more significant.
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Objective To study the effect of continuous positive airway pressure (CPAP) treatment on the endothelial function in patients with obstructive sleep apnea (OSA). Methods This study strictly followed the PRISMA principle. PubMed, Web of Science and the Cochrane Collaboration Database were searched on randomized controlled trials (RCT) which assessed the effects of CPAP on endothelial function of OSA patients from 1992 to 2013. The parameters of endothelial function evaluation included endothelium-dependent vasodilation function (EDV) and endothelium-independent vasodilation function (EIV). EDV was used to detect flow mediated dilation (FMD) and reactive hyperemia index (RHI), and EIV was used to detect nitroglycerin-induced dilation (GTN-ID). Results A total of 4 articles (137 patients) were selected. Meta-analysis results showed that CPAP significantly altered the overall EDV: standardized mean difference ( SMD )＝1.42, 95% CI 0.45 to 2.38, P＝0.004; and the FMD was significantly improved: weighed mean difference ( WMD ) ＝ 3.94, 95% CI 1.30 to 6.57, P ＝ 0.003. CPAP did not significantly alter the GTN-ID: WMD ＝ -0.71, 95% CI 2.69 to 1.26, P ＝ 0.48. Conclusions Using CPAP to treat OSA patients is beneficial to promoting overall EDV improvement, but the EIV has not improved significantly.
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Objective To compare positron emission tomography/computed tomography(PET/CT)vs.endobronchial ultra-sound-guided transbronchial needle aspiration(EBUS-TBNA)in evaluating lymph node metastasis in NSCLC.Methods We col-lected 79 NSCLC patients with enlarged mediastinal lymph nodes(diameter >1 cm by CT).The diagnostic values of PET/CT scanning and EBUS-TBNA for mediastinal staging were evaluated.Subgroup analysis according to histologic type was per-formed.Results There were 22 patients of N1 stage and 28 patients of N2 in these 79 cases.In the N1 patients,PET/CT's sen-sitivity and specificity was 59.1% and 75.4%,respectively.EBUS-TBNA's sensitivity and specificity was 86.4% and 100.0%,respectively.In the N2 patients,PET/CT's sensitivity and specificity was 67.9% and 76.5% and EBUS-TBNA's sensitivity and specificity was 89.3% and 100.0%.Conclusion EBUS-TBNA is more accurate than PET/CT in evaluating the metastatic condition of patients,and EBUS-TBNA can also benefit PET/CT(-)patients with adenocarcinoma.
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Objective To investigate the expression of miR-200b in lung cancer and its relationship with clinicopathological features of lung cancer.Methods The specimens of lung tumor tissue and adjacent normal lung tissue of 36 cases of lung cancer who received surgical treatment in our department were collected,and then quantitative real time PCR (qRT-PCR) was applied to determine the expression of miR-200b in lung cancer tissue and adjacent normal lung tissue.Results The expression of miR-200b in lung cancer was significantly lower than adjacent normal lung tissue (P =0.000),and in small cell lung cancer was also significantly lower than adenocarcinoma and squamous cell carcinoma (0.13 ± 0.09 vs.0.64 ± 0.33,0.75 ± 0.30) (P =0.005 and P =0.001).The expression of miR-200b in patients with positive lymph nodes,advanced stage of lung cancer and in smokers were significantly lower than those with negative lymph nodes,early stage of lung cancer and in non-smokers,respectively (0.52 ± 0.29 vs.0.87 ± 0.35,0.46 ±0.25 vs.0.90 ±0.32,0.52 ±0.27 vs.0.90 ±0.39) (P =0.004,P =0.000 and P =0.015).Conclusions Low expression of miR-200b may participate in the occurrence and progression of lung cancer,especially in small cell lung cancer,and correlates with the metastasis of lung cancer.The down-regulated expression of miR-200b may be induced by smoking.Thus,miR-200b perhaps is a new target for the treatment of lung cancer.
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Insulin-like growth factors (IGF), regulated by their receptors and binding proteins, play a pivotal role in human cell proliferation, differentiation and apoptosis. Increasing evidence has revealed that IGF system is involved in the genesis and progress of various malignancies including lung cancer. Recent studies in regard to IGF axis expression in the lung cancer cell lines, pulmonary tissue samples and blood circulation of lung cancer patients have shown that the IGF axis may contribute to the transformation and progression of lung cancer. Several researches have shown that a number of drugs targeting the IGF receptor are being investigated in clinical trials and suggest a potential therapeutic efficacy. This article reviews the updates and progress in the research of IGF axis in lung cancer.