Activation of the PPARγ/NF-κB pathway by A-MPDA@Fe3O4@PVP via scavenging reactive oxygen species to alleviate hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (IRI) is a common pathological process during hepatectomy and liver transplantation and the two primary reasons for hepatic IRI are reactive oxygen species (ROS)-mediated oxidative stress and excessive inflammatory responses. Herein, a novel antioxidant nanodrug (A-MPDA@Fe3O4@PVP) is prepared by employing L-arginine-doped mesoporous polydopamine (A-MPDA) nanoparticles as the carrier for deposition of ultra-small ferric oxide (Fe3O4) nanoparticles and further surface modification with polyvinylpyrrolidone (PVP). A-MPDA@Fe3O4@PVP not only effectively reduces the aggregation of ultra-small Fe3O4, but also simultaneously replicates the catalytic activity of catalase (CAT) and superoxide dismutase (SOD). A-MPDA@Fe3O4@PVP with good antioxidant activity can rapidly remove various toxic reactive oxygen species (ROS) and effectively regulate macrophage polarization in vitro. In the treatment of hepatic IRI, A-MPDA@Fe3O4@PVP effectively alleviates ROS-induced oxidative stress, reduces the expression of inflammatory factors, and prevents apoptosis of hepatocytes through immune regulation. A-MPDA@Fe3O4@PVP can further protect liver tissue by activating the PPARγ/NF-κB pathway. This multiplex antioxidant enzyme therapy can provide new references for the treatment of IRI in organ transplantation and other ROS-related injuries such as fibrosis, cirrhosis, and bacterial and hepatic viral infection.

Overexpression of NtLHT1 affects the development of leaf morphology and abiotic tolerance in tobacco.

LYSINE HISTIDINE TRANSPORTER1 (LHT1) is a crucial broad-specificity and high-affinity amino acid transporter affecting the uptake of nitrogen and probably the tolerance to abiotic stress in plants. However, little is known about the phenotypic functions of LHT1 in plant growth and development and abiotic stress tolerance. In this study, we identified the NtLHT1 gene from the tobacco variety Honghuadajinyuan (HD) and determined its important roles in leaf morphological development and plant resistance to abiotic stress. Comprehensive functional analyses using knockout and overexpression transgenic lines (ntlht1 and OE) revealed overexpression of NtLHT1 accelerated leave senescence and increased plant height, leaf number and plant tolerance under cold, salt and drought stresses. In addition, NtLHT1 overexpression significantly decreased the leaf elongation of HD, causing the leaves to change from a long-elliptical shape to an elliptical shape. However silencing NtLHT1 decreased the seed germination rate under NaCl and PEG stresses. Moreover, NtLHT1 significantly affected the contents of various amino acids, such as the neutral, acidic, non-polar and aromatic amino acids, ethylene precursor (ACC), GA3 and IAA in tobacco. These results suggested that the amino acid and ethylene precursor ACC transport activities of NtLHT1 provide fine regulatory function for plant growth and development and plant tolerance to abiotic stress.

Enrollment Success, Factors, and Prediction Models in Cancer Trials (2008-2019).

PURPOSE: To investigate the enrollment success rate of cancer clinical trials conducted in 2008-2019 and various factors lowering the enrollment success rate. METHODS: This is a cross-sectional study with clinical trial information from the largest registration database ClinicalTrials.gov. Enrollment success rate was defined as actual enrollment greater or equal to 85% of the estimated enrollment goal. The association between trial characteristics and enrollment success was evaluated using the multivariable logistic regression. RESULTS: A total of 4,004 trials in breast, lung, and colorectal cancers were included. The overall enrollment success rate was 49.1%. Compared with 2008-2010 (51.5%) and 2011-2013 (52.1%), the enrollment success rate is lower in 2014-2016 (46.5%) and 2017-2019 (36.4%). Regression analyses found trial activation year, phase I, phase I/phase II, and phase II (v phase III), sponsor agency of government (v industry), not requiring healthy volunteers, and estimated enrollment of 50-100, 100-200, 200, and >500 (v 0-50) were associated with a lower enrollment success rate (P < .05). However, trials with placebo comparator, ≥5 locations (v 1 location), and a higher number of secondary end points (eg, ≥5 v 0) were associated with a higher enrollment success rate (P < .05). The AUC for prediction of the final logistic regression models for all trials and specific trial groups ranged from 0.69 to 0.76. CONCLUSION: This large-scale study supports a lower enrollment success rate over years in cancer clinical trials. Identified factors for enrollment success can be used to develop and improve recruitment strategies for future cancer trials.

Global trends in the burden of esophageal cancer, 1990-2019: results from the Global Burden of Disease Study 2019.

Background: Esophageal cancer is one of the leading causes of cancer death worldwide. A deeper understanding of the trends in annual incidence, mortality, and disability-adjusted life-years (DALYs) of esophageal cancer is critical for management and prevention. In this study, we report on the disease burden of esophageal cancer in 204 countries and territories between 1990 and 2019 by age, sex, and sociodemographic index (SDI). Methods: Data on incidence, mortality, and DALYs were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The estimated numbers and age-standardized rates for esophageal cancer in 2019 are presented in this paper, as well as trends from 1990 to 2019. All estimates are presented as counts and age-standardized rates per 100,000 population, with 95% uncertainty intervals (UIs) for each estimate. Results: In 2019, nearly 535,000 (95% UI: 467,000-595,000) new cases of esophageal cancer occurred globally. Esophageal cancer was responsible for more than 498,000 (95% UI: 438,000-551,000) deaths and 11.7 million (95% UI: 10.4-12.9 million) DALYs. Worldwide age-standardized rates of esophageal cancer, including incidence, deaths, and DALYs, have declined since 1990. However, the trends differ across countries and territories. Notably, there was a nonlinear but generally inverse correlation between age-standardized DALY rates and SDI. Higher age-standardized incidence and death rates were observed in males compared to females, and both increased with age. Regarding risk factors, smoking, alcohol use, and high body-mass index were 3 predominant contributors to esophageal cancer DALYs in 2019 for both sexes worldwide. Conclusions: This study found a global reduction in the esophageal cancer burden, but substantial heterogeneity remains across regions and countries. Hence, the identification of high-risk groups and the exploration of specific local strategies and primary prevention efforts are required.

Effectiveness and implementation of models of cancer survivorship care: an overview of systematic reviews.

PURPOSE: To critically assess the effectiveness and implementation of different models of post-treatment cancer survivorship care compared to specialist-led models of survivorship care assessed in published systematic reviews. METHODS: MEDLINE, CINAHL, Embase, and Cochrane CENTRAL databases were searched from January 2005 to May 2021. Systematic reviews that compared at least two models of cancer survivorship care were included. Article selection, data extraction, and critical appraisal were conducted independently by two authors. The models were evaluated according to cancer survivorship care domains, patient and caregiver experience, communication and decision-making, care coordination, quality of life, healthcare utilization, costs, and mortality. Barriers and facilitators to implementation were also synthesized. RESULTS: Twelve systematic reviews were included, capturing 53 primary studies. Effectiveness for managing survivors' physical and psychosocial outcomes was found to be no different across models. Nurse-led and primary care provider-led models may produce cost savings to cancer survivors and healthcare systems. Barriers to the implementation of different models of care included limited resources, communication, and care coordination, while facilitators included survivor engagement, planning, and flexible services. CONCLUSIONS: Despite evidence regarding the equivalent effectiveness of nurse-led, primary care-led, or shared care models, these models are not widely adopted, and evidence-based recommendations to guide implementation are required. Further research is needed to address effectiveness in understudied domains of care and outcomes and across different population groups. IMPLICATIONS FOR CANCER SURVIVORS: Rather than aiming for an optimal "one-size fits all" model of survivorship care, applying the most appropriate model in distinct contexts can improve outcomes and healthcare efficiency.

Beta-glucan enhanced immune response to Newcastle disease vaccine and changed mRNA expression of spleen in chickens.

The present study was performed to investigate the effect of oral administration of ß-glucan (G70), a product obtained from the cell wall of yeast, on Newcastle disease virus (NDV)-specific hemagglutination inhibition (HI) titers, lymphocyte proliferation, and the role of T lymphocyte subpopulations in chickens treated with live NDV vaccine. In addition, the influence of ß-glucan on splenic gene expression was investigated by transcriptome sequencing. The results revealed that the supplementation of ß-glucan boosted the titer of serum NDV HI increased the NDV stimulation index of lymphocytes in peripheral blood and intestinal tract, and promoted the differentiation of T lymphocytes into CD4+ T cells. The RNA sequencing (RNA-seq) analysis demonstrated that G70 upregulated the mRNA expressions related to G-protein coupled receptor and MHC class I polypeptide, and downregulated the mRNA expressions related to cathelicidin and beta-defensin. The immunomodulatory effect of G70 might function through mitogen-activated protein kinase signaling pathway. To sum up, G70 could boost the immunological efficacy of live NDV vaccine in chickens and could be applied as a potential adjuvant candidate in the poultry industry.

Characteristics of toxicity occurrence patterns in concurrent chemoradiotherapy after induction chemotherapy for patients with locally advanced non-small cell lung cancer: a pooled analysis based on individual patient data of CALGB/Alliance trials.

Background: For patients with locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy is the foundational treatment strategy. Adding induction chemotherapy did not achieve a superior efficacy but increased the burden from toxicity. Accordingly, we retrospectively investigated the toxicity patterns through pooling individual patient data of the Cancer and Leukemia Group B (CALGB)/Alliance trials. Methods: We included a total of 637 patients with unresectable stage III NSCLC who received induction chemotherapy with a platinum doublet and concurrent chemoradiotherapy and experienced at least one adverse event (AE) in CALGB 9130, 9431, 9534, 30105, 30106 and 39801 trials. The following toxicity occurrence patterns were evaluated: top 10 most frequent AEs, AE distribution by grade, rate of treatment discontinuation due to AEs, associations of AE occurrence with patient characteristics and treatment phase, the time to the first grade ≥3 AE occurrence and its associations with patient characteristics and treatment phase. Results: The occurrence of AEs was the main reason accounting for treatment discontinuation (60 of 637 among all patients; 18 of 112 patients who experienced the induction phase only; 42 of 525 patients who experienced both phases). All patients experienced a total of 11,786 AEs (grade ≥3: 1,049 of 5,538 in induction phase, 1,382 of 6,248 in concurrent phase). Lymphocytes and white blood count were of top 3 grade ≥3 AEs that patients experienced the most in the either phase. Multivariable analysis found AE occurrence was associated with age ≥65 [any grade: odds ratio (OR) =1.44, 95% confidence interval (CI): 1.12-1.86] and the concurrent phase (grade ≥3: OR =1.86, 95% CI: 1.41-2.47; any grade: OR =1.47, 95% CI: 1.19-1.81). Patients in the concurrent phase were more likely and earlier to develop grade ≥3 AEs than those in the induction phase [hazard ratio (HR) =4.37, 95% CI: 2.52-7.59]. Conclusions: The report provides a better understanding regarding the toxicity occurrence patterns in concurrent chemoradiotherapy after induction chemotherapy.

Minimum Volume Standards for Surgical Care of Early-Stage Lung Cancer: A Cost-Effectiveness Analysis.

BACKGROUND: Multiple stakeholders have advocated for minimum volume standards for complex surgical procedures. The Leapfrog Group recommends that patients with non-small cell lung cancer (NSCLC) receive surgical resection at hospitals that perform at least 40 lung resections annually. However, the cost-effectiveness of this paradigm is unknown. METHODS: A cost-effectiveness analysis was performed on 90-day and 5-year horizons for patients with clinical stage I NSCLC undergoing surgical resection at hospitals stratified by Leapfrog standard. Model inputs were derived from either the literature or a propensity score-matched cohort using the National Cancer Database. For the 5-year horizon, we simulated using a Markov model with 1-year cycle. Incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. RESULTS: For the 90-day horizon, resection at a Leapfrog hospital was more costly ($25 567 vs $25 530) but had greater utility (0.185 vs 0.181 quality-adjusted life-years), resulting in an ICER of 10 506. Similarly, for the 5-year horizon, resection at a Leapfrog hospital was more costly ($26 600 vs $26 495) but more effective (3.216 vs 3.122 quality-adjusted life-years), resulting in an ICER of 1108. When the costs for long-distance travel, lodging, and loss of productivity for caregivers were factored in, the ICER was 20 499 during the 5-year horizon for resection at Leapfrog hospitals. Using a willingness-to-pay threshold of $50 000, resection at a Leapfrog hospital remained cost-effective. CONCLUSIONS: Receiving surgery for clinical stage I NSCLC at hospitals that meet Leapfrog volume standards is cost-effective. Payers and policymakers should consider supporting patient and caregiver travel to higher volume institutions for lung cancer surgery.

Pan-Driver-Negatives versus Epidermal Growth Factor Receptor Mutants for C-Stage IA Lung Adenocarcinoma with Ground-Glass Opacity.

PURPOSE: We aimed to verify the prognosis of epidermal growth factor receptor (EGFR) mutation of clinical (c)-stage IA lung adenocarcinoma with the ground-glass opacity (GGO) component. METHODS: We evaluated 226 cases of surgically resected c-stage IA lung adenocarcinoma with GGO component. Endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis and the log-rank test were used to estimate the survival differences. Prognostic factors were assessed using the univariable and multivariable Cox proportional hazards model. RESULTS: Among the 226 cases, 177 cases harbored the EGFR-mutant adenocarcinoma with the GGO component. The mean duration of follow-up time was 54.4 ± 1.2 months. The 5-year OS and RFS did not differ significantly between the EGFR-mutant and wild-type groups (5-year OS 100% vs. 94.3%, hazard ratio [HR] 0.276, P = 0.168; 5-year RFS 94.7% vs. 95.7%, HR 0.873, P = 0.864). Multivariable Cox hazard model revealed that radiologically solid component size (P = 0.010) and pathological node-positive (P = 0.036) were significant predictors of an inferior RFS. CONCLUSION: EGFR-mutant was not a prognostic factor of OS and RFS for c-stage IA lung adenocarcinoma with the GGO component. Radiologically solid component size and pathological lymph node status were independent prognostic factors of worse RFS.

Damage-Free and Time-Saving Platform Integrated by a Flow Membrane Separation Device and a Dual-Target Biofuel Cell-Based Biosensor for Continuous Sorting and Detection of Exosomes and Host Cells in Human Serum.

The growth relationship between exosomes (EXOs) and the host cells is highly desired for tumor evaluations, which puts forward high demand on the accurate and convenient acquisition of their individual quantitative information. However, the tedious and destructive separation process and the requirement of dual-channel detection make it become an extremely challenging task. Herein, we integrated an enzymatic biofuel cell (EBFC)-powered biosensor with a flow cell-supported membrane separation device (FMSC) to develop a continuous separation and detection platform for EXOs and host cancer cells in human serum. The FMSC equipped with an aluminum oxide membrane served as a size-dependent sorting unit to nondestructively extract EXOs from human serum within 5 min, representing a 99.3% reduction in isolating time compared to ultracentrifugation. The EBFC-powered biosensors modified with different aptamers on anodes and cathodes were used as a dual-channel sensing unit. By regulating the controlling valves of different fluid passages, the extracted EXOs and residual host cells could be successively inputted into EBFC-powered biosensors, which generated a segmental degradation in output performance due to the EXO-and host cell-caused increase in the steric hindrance of anodes and cathodes, respectively. Based on these degradations, we obtained the quantitative information of EXOs and host cells with a record-breaking sensitivity (EXOs: 5.59 × 103 particles/mL and host cells: 25 cells/mL). Moreover, the growth relationship between EXOs and host cells was also built, which would be beneficial for the disclosure of the growth state or even more detailed biology information of tumor.

Time to diagnosis and treatment of lung cancer: A systematic overview of risk factors, interventions and impact on patient outcomes.

Over half of patients with lung cancer are diagnosed at a stage when curative treatment is not possible, suggesting an earlier diagnosis could improve outcomes. This comprehensive overview summarises the evidence on 1) times to diagnosis and treatment, 2) their impact on patient outcomes, 3) risk factors and 4) interventions to reduce time intervals, and 5) key methodological issues in such studies. Eligible articles were relevant systematic or scoping reviews and meta-analyses, searched via PubMed, Embase, Web of Science, and Cochrane Library; published from database inception to 6 August 2020 (PROSPERO identifier: CRD42020203530). A total of 18 systematic and scoping reviews were included. Times to diagnosis and treatment significantly varied and were often longer than recommended in international guidelines. Results regarding the impact of time intervals on survival or tumour stage indicated mixed associations (positive, negative, or no); in each review, however, more studies reported either no or negative association. Risk factors were considerable, categorized at the disease, patient, healthcare provider and system levels. Interventions including fast-access diagnosis programs, patient navigation and multidisciplinary strategies were effective in reducing times to diagnosis and treatment. Methodological issues included large variations in interval definitions and summary measures, lack of addressing an important potential source of bias-the "waiting time paradox"-and few studies of trends over time of these intervals. The current evidence indicates that patients with lung cancer experience diagnosis and treatment delays given guidelines' recommendations, but there are inconsistent findings about the association between times to diagnosis and treatment and patient outcomes. This is partially due to variations in definitions of time intervals, and limitations in analytic approaches that fail to account for a potential waiting time paradox. The identified risk factors and effective interventions demonstrate the potential for improvements in addressing diagnostic and treatment delays, regionally and globally.

CRISPR System-Linked Self-Assembling Nanoplatforms for Inspection and Screening of Gastric Cancer Stem Cells.

Cancer stem cells (CSCs) possess a high degree of plasticity, constituting a formidable challenge to identify and screen CSCs in situ with outstanding specificity and sensitivity. To overcome this limitation, a self-assembled heterodimer consisting of clustered regularly interspaced short palindromic repeats/Cas12a (named A-CCA) linkage is designed for in situ identification and screening of gastric CSCs (GCSCs) from gastric cancer cells (GCCs). In this system, the editable character of crRNA performs recognition of dual-targets in GCSCs, effectively boosting the specificity of identification, while the enzymatic reaction of Cas12a contributes meaningfully to the sensitivity of sensing, enabling in situ examination and screening of GCSCs. Specifically, the A-CCA nanoplatforms hybridized with ABCG 2 and ABCB 1 overexpress in GCSCs, which can generate heterodimers and simultaneously restore the function of trans-cleavage. At this time, the asymmetry of the heterodimer causes a circular dichroism signal, which together with the recovered fluorescence signal form a dual-signals output system that can further ensure the precision of screening GCSC. Therefore, fluorescence-enhanced GCSCs can be sorted out from GCCs by flow cytometry. Furthermore, GCSCs screened by this assay possess extremely aggressive tumorigenic efficiency, providing a fundamental research object for further developing CSC targeted drugs in vivo.

Effect of High-Flow Nasal Cannula for Hypoxemia Following Sun's Procedure in Acute Aortic Dissection Type a Patients.

Background: Patients with acute aortic dissection type A (AADA) often have hypoxemia (partial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2] <300 mmHg) before weaning in the intensive care unit (ICU). This study compared the efficacy of high-flow nasal cannula (HFNC) with that of conventional oxygen therapy (COT) in patients with AADA following Sun's procedure. Methods: The medical records of 87 adult patients with AADA who underwent Sun's procedure and met the inclusion criteria (PaO2/FiO2 <300 mmHg before weaning) were retrospectively analyzed. After surgery, 41 patients were treated with HFNC and 46 were treated with COT. The oxygenation level, FiO2, partial pressure of carbon dioxide, heart rate, respiratory rate, subjective discomfort, and reintubation rate were recorded. The difference in lung volume loss between the HFNC and COT groups was assessed using the radiological atelectasis score (chest radiograph) or calculated from three-dimensional (3D) reconstructed computed tomography (CT) images. Results: From day 1 to day 5 after weaning, there was no significant difference in PaO2/FiO2 between the HFNC and COT groups, although the FiO2 was significantly lower in the HFNC group than in the COT group (P < 0.05). Further studies indicated that the percentage of lung volume loss (pleural effusion and/or pulmonary atelectasis) by 3D reconstruction of CT images at 4-8 days post-operation was significantly lower in the HFNC group (P < 0.05). The subjective experience of breathing discomfort, reintubation rate, and length of stay in the ICU were significantly reduced in the HFNC group (P < 0.05). There was no significant difference in readmission to the ICU and in-hospital mortality between the two groups. Conclusions: HFNC can be used as an effective oxygen therapy for AADA patients with hypoxemia after Sun's procedure.

Effect of the Mendelsohn maneuver and swallowing training in patients with senile vascular dementia complicated with dysphagia.

OBJECTIVE: We investigated the effect of the Mendelsohn maneuver and swallowing training in patients with senile vascular dementia complicated with dysphagia. METHODS: We randomly classified 214 patients with senile vascular dementia and swallowing dysfunction into a control group (CG, n = 106) and observation group (OG, n = 108). Both groups underwent health education, psychological intervention, and training of the oral muscle group. The OG additionally underwent the Mendelsohn maneuver and swallowing training. The Hasegawa Dementia Scale (HDS), China Stroke Scale (CSS), and Neurobehavioral Cognitive Status Examination (NCSE) were used to evaluate dementia, neurological impairment, and cognitive dysfunction, respectively. RESULTS: The OG had a higher rate of effective therapy than the CG. After intervention, the OG showed better swallowing function than the CG. At 15 days and 1 month after intervention, the OG had higher video fluoroscopic swallowing exam scores than the CG. The OG had lower serum interleukin (IL)-1, IL-6, and tumor necrosis factor-α levels than the CG. After intervention, the OG had higher HDS and NCSE scores and lower CSS scores than the CG. CONCLUSIONS: The Mendelsohn maneuver and swallowing training can improve swallowing function in patients with senile vascular dementia complicated with dysphagia and help to ameliorate the inflammatory response.

Papaverine Perfusion via the Aortic Root before Heart Re-beating Alleviates Myocardial Injury after Heart Valve Replacement.

AIM: Myocardial injury is inevitable during cardiac surgical procedures and reducing myocardial injury in patients with CPB surgery is the focus of current research. Papaverine is accepted as an ideal coronary vasodilator. This study was to estimate the effect of papaverine perfusion via the aortic root before heart re-beating on patients undergoing heart valve replacement. METHODS: All the patients enrolled in this study were admitted during 2013-2015. The basic clinical characteristics of the patients preoperative, intraoperative, and postoperative were compared. The immunochemistry assays and enzyme-linked immunosorbent assay (ELISA) were performed to assess the serum biomarkers. Western blot and immunohistochemistry (IHC) were undertaken to detect the expression of associated proteins. RESULTS: Patients receiving papaverine perfusion via the aortic root before heart re-beating during heart valve replacement surgery under CPB showed less extracorporeal circulation time and CPB time, higher automatic heartbeat recovery rate, less mechanical ventilation time, shorter ICU and in-hospital stay, less leak of cTnI and CK-MB, and weaker inflammatory response than the patients in control group. In addition, the protein expression of IL-6/8/10 and TNF-α was reduced by the perfusion of papaverine. The IHC staining for NFκB was depressed in papaverine group. CONCLUSION: Papaverine perfusion presented positive effect during valve replacement; this cardioprotective effect may be associated with inhibition of inflammatory response and NF-κB. These findings provided new clues for reduction of myocardial injury during cardiac surgery.

Comparison of first-generation EGFR-TKIs (gefitinib, erlotinib, and icotinib) as adjuvant therapy in resected NSCLC patients with sensitive EGFR mutations.

BACKGROUND: Several randomized controlled trials have suggested that adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were associated with prolonged disease-free survival (DFS) in EGFR-mutated NSCLC patients after radical resection, comparing with chemotherapy or placebo. We aimed to compare the effectiveness of different first-generation EGFR-TKIs as adjuvant treatment in real-world setting. METHODS: Early-stage EGFR mutated NSCLC patients who underwent radical resection and treated with first-generation EGFR-TKIs (gefitinib, erlotinib, icotinib) as adjuvant therapy between Feb 2010 and Jan 2019 were retrieved from a prospectively-maintained database in our center. The primary endpoint was DFS in stage II/III (TNM 8th) patients with exploratory endpoint regarding DFS in stage I patients. Sensitivity analyses were based on propensity score matched (PSM) cohorts. Treatment failure patterns among different TKIs were also compared. RESULTS: Of 588 eligible patients, 198 patients (33.7%) received gefitinib, 106 patients (17.9%) received erlotinib, and 284 patients (48.2%) received icotinib. The median DFS of stage II/III patients in the gefitinib, erlotinib and icotinib group were 36.1 months (95% CI, 23.9-49.4), 42.8 months (95% CI, 29.6-97.8), and 32.5 months (95% CI, 23.9-49.4), respectively, with no significant difference (log-rank test P=0.22). There was also no significant difference in DFS among stage I patients receiving different TKIs (P=0.12). PSM adjustments and multivariate analyses adjusting for other confounders revealed similar results. In addition, there were no significant differences in treatment failure pattens in different EGFR-TKI arms, especially in terms of brain metastases (6.1% in gefitinb, 7.5% in erlotinib, 3.9% in icotinib) and bone metastases (8.6% in gefitinb, 9.4% in erlotinib, 7.0% in icotinib). CONCLUSIONS: This first and largest real-world study showed that gefitinib, erlotinib, and icotinib demonstrated comparable clinical effectiveness as adjuvant therapy for patients with early-stage EGFR mutated NSCLC.

Dysregulated circRNA_100876 contributes to proliferation and metastasis of colorectal cancer by targeting microRNA-516b (miR-516b).

Colorectal cancer (CRC) is globally one of the most common malignant tumors. Increasing number of studies indicate that circular RNAs (circRNAs) play a significant role in the initiation and progression of CRC. However, the role of circRNA_100876 in CRC progression remains unclear. In this study, we investigated the expression and function of circRNA_100876 in CRC progression. The expression of circRNA_100876 and microRNA-516b (miR-516b) was compared in normal and CRC tissues using quantitative real-time polymerase chain reaction (RT-qPCR). In addition, proliferation, metastasis, and apoptosis of the cells were analyzed using Cell Counting Kit-8 (CCK-8) assay, Transwell assay, and flow cytometry, respectively. The relationship between circRNA_100876 and miR-516b was further verified using dual-luciferase reporter assay. Our data showed that circRNA_100876 was highly expressed in CRC tumor tissues, and the high expression gtransition (EMT)-related proteins. Furthermore, we found that the addition of miR-516b reversed the anti-tumor effect induced by the downregulation of circRNA_100876. In conclusion, this study revealed that circRNA_100876 is overexpressed in CRC tissues and represents a promising therapeutic target for CRC.