BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Objective To investigate the risk factors of acute kidney injury(AKI) after intracoronary stent implantation in order to provide the basis for clinical prophylaxis and treatment.Methods Retrospectively analyzed 626 consecutive patients who underwent isolated intracoronary stent implantation in our institution from January 2007 to July 2011.Multivariate logistic regression model was constructed to identify the risk factors for the development of AKI defined as a serum creatinine (SCr) 130 to 199 μ mol/L or estimated creatinine clearance(Ccr) 30 to 60 ml/min per 1.73 m2.Results Ninety-three patients of 626 (14.9％) underwent isolated intracoronary stent implantation developed AKI.The results of the multivariate forward stepwise logistic regression analysis found that risk factors for the development of AKI following isolated intra-coronary stent implantation was associated with age (OR =1.570,95％ CI 1.308-1.885),ejection fraction (EF) ≤ 30％(OR =11.526,95％ CI 2.452-54.177),hypotension during perioperative and postoperation (OR =11.074,95％ CI 2.439-50.282),operation duration(OR =1.032,95％ CI 1.012-1.051),sex (OR =0.010,95％ CI 0.001-0.086),NYHA class Ⅲ & Ⅳ (OR =0.209,95％ CI 0.059-0.737),peripheral vascular disease (OR =0.528,95％ CI 0.286-0.973),chronic obstructive pulmonary diseases (OR =0.546,95％ CI 0.304-0.982),preoperation Cr (OR=1.418,95％CI 1.216-1.654) (and all P＜0.05).Conclusion AKI is the common complications after intracoronary stent implantation,especially age,EF ≤ 30％,hypotension during perioperative and postoperation,operation duration are independent risk factors.

BACKGROUNDOwing to the limitation of monolayer tumour cells or transplanted tumor in radiation biology, multicellular spheroid (MTS) as a model of entity tumor had a wide range of application. This research aims to study the growth characteristics of A549 lung adenocarcinoma MTS so as to choose the best ones to perform experiments.

METHODS1.75×10⁷ A549 cells in 35mL were transfered into the 100mm incubator sealed with 2% agarose to have a rotating culture with 60r/min. After 40 hours every MTS was transfered into each of the 96 wells of multi-well plates coated with 2% agarose to have a static culture.

RESULTSDuring the rotation stage the MTS was round, the size was uniform, and the conjunction between cells was loose. After about 10 days of static culture, when the diameter of MTS at 429 to 570 μm the conjunction was close. After 26.5 days of static culture, the diameter of MTS became 1358.5 μm which could not be used for experiment. Observed under electron microscopy the cells in the MTS grew well without any apoptosis and necrosis. The cell cycle of MTS was dominated by G0 and G1 stage.

CONCLUSIONSCombination of rotating and static culture is a simple method to produce MTS which has similar growth characteristics with entity tumor and is best suitable for experiment research when the diameter is about 500 μm.