Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges.

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.

Two birds with one stone: facile fabrication of an iron-cobalt bimetallic sulfide nanosheet-assembled nanosphere for efficient energy storage and hydrogen evolution.

Transition metal sulfides are widely regarded as the most promising electrode materials for supercapacitors. Herein, we utilized a straightforward electrodeposition method to prepare an iron-cobalt bimetallic sulfide nanosheet-assembled nanosphere on nickel foam (FeCo2S4/NF). The synergistic effect between bimetals and the unique three-dimensional structure significantly improved its capacitive performance. As a result, it demonstrated a remarkable specific capacitance, brilliant long-term stability and acceptable rate capability. Moreover, FeCo2S4/NF and active carbon (AC) were used to assemble an asymmetric supercapacitor (ASC), and FeCo2S4//AC displays a maximum energy density of 29.4 W h kg-1 at 800 W kg-1. Moreover, when adopted as an electrocatalyst for the hydrogen evolution reaction (HER), FeCo2S4/NF exhibited excellent catalytic properties (η10 = 165 mV). Our research provides a valuable insight into the multidisciplinary integration of high-performance energy materials.

Correlation of immune inflammatory indices and nutritional risk index with prognosis in patients with non-small cell lung cancer.

OBJECTIVE: To investigate the relationship of lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and nutritional risk index (NRI) with the prognosis of non-small cell lung cancer (NSCLC). METHODS: The clinical data of 400 NSCLC patients undergoing surgery at Shaoxing Shangyu Hospital of Traditional Chinese Medicine from January 2019 to June 2022 were collected for this retrospective analysis. The optimal cutoff values for NLR, PLR, LMR and NRI were determined using receiver operating characteristic (ROC) curves. The patients were grouped according to the optimal cutoff values, and the clinicopathological characteristics were compared between groups. The Kaplan-Meier survival curve and Cox risk model were used to identify the independent risk factors affecting the prognosis of patients with NSCLC. A nomogram risk prediction model was constructed and its effectiveness was verified. RESULTS: ROC curve analysis revealed that the area under the curve (AUC) values for NLR, PLR, LMR and NRI in predicting overall survival of NSCLC patients were 0.827, 0.753, 0.719 and 0.770, respectively. The optimal cutoff values for NLR, PLR, LMR and NRI were 2.49, 126.32, 3.02 and 89, respectively. Survival analysis found that the survival time was shorter in patients with NLR>2.49, PLR>126.32, LMR>3.02 and NRI≤89. Results from Cox model indicated that TNM staging, NLR>2.49, LMR>3.02, NRI≤89, surgical method, intraoperative blood loss, postoperative complication, and adjuvant chemotherapy were risk factors affecting the prognosis of NSCLC patients. A nomogram was constructed based on the results of multivariate analysis. The AUC of the nomogram was 0.967 (95% CI: 0.943-0.992) and 0.948 (95% CI: 0.874-1) in the training set and the test set, respectively. The C-index was 0.90 and 0.89, respectively. The calibration curve demonstrated good agreement between the predicted values of the nomogram and the actual observed values. CONCLUSION: NLR, LMR and NRI are significant predictors of the prognosis of patients with NSCLC. NLR>2.49, LMR>3.02, and NRI≤89 are risk factors for the prognosis of NSCLC patients.

IKZF3 is a novel prognostic biomarker for head and neck squamous cell carcinoma: A study based on bioinformatics analysis.

In the past few years, immunotherapy of tumors has become an extensive research hotspot, and the value of IKZF family genes in the tumor microenvironment has also been increasingly recognized. However, the expression of the IKAROS family zinc finger 3 (IKZF3) gene in human head and neck squamous cell carcinoma (HNSCC) and its prognostic value were not reported for the main subset until now. In the present study, we analyzed the relationship between IKZF3 gene expression and the survival of HNSCC patients. To evaluate the potential of IKZF3 as a prognostic biomarker for HNSCC comprehensively, multiple online analysis tools, including UALCAN, cBioPortal, GEPIA, WebGestalt, String, Genomic Data Commons, and TIMER databases were utilized in our study. We observed that the HNSCC patients with higher IKZF3 expression tended to exhibit longer overall survival. Univariate and multivariate Cox regression analyses indicated that age and grade were independent prognostic indicators in HNSCC. Moreover, Gene Ontology and KEGG function enrichment analyses showed that several pathways in HNSCC might be pivotal pathways regulated by IKZF3, which revealed that IKZF3 was probably participating in the occurrence and development of HNSCC. Furthermore, the hypomethylation of the IKZF3 gene was closely associated with genes that observed mutation in HNSCC. IKZF3 was significantly correlated with several immune cells in HNSCC (e.g., CD8+ T cell, CD4+ cell, and dendritic cell). We explored the potential prognostic values and roles of the IKZF3 in HNSCC, revealing that IKZF3 was probably a novel and reliable prognostic biomarker for patients with HNSCC.

Rapid Detection of Aspergillus flavus and Quantitative Determination of Aflatoxin B1 in Grain Crops Using a Portable Raman Spectrometer Combined with Colloidal Au Nanoparticles.

Aspergillus flavus and Aflatoxins in grain crops give rise to a serious threat to food security and cause huge economic losses. In particular, aflatoxin B1 has been identified as a Class I carcinogen to humans by the International Agency for Research on Cancer (IARC). Compared with conventional methods, Surface-Enhanced Raman Scattering (SERS) has paved the way for the detection of Aspergillus flavus and Aflatoxins in grain crops as it is a rapid, nondestructive, and sensitive analytical method. In this work, the rapid detection of Aspergillus flavus and quantification of Aflatoxin B1 in grain crops were performed by using a portable Raman spectrometer combined with colloidal Au nanoparticles (AuNPs). With the increase of the concentration of Aspergillus flavus spore suspension in the range of 102-108 CFU/mL, the better the combination of Aspergillus flavus spores and AuNPs, the better the enhancement effect of AuNPs solution on the Aspergillus flavus. A series of different concentrations of aflatoxin B1 methanol solution combined with AuNPs were determined based on SERS and their spectra were similar to that of solid powder. Moreover, the characteristic peak increased gradually with the increase of concentration in the range of 0.0005-0.01 mg/L and the determination limit was 0.0005 mg/L, which was verified by HPLC in ppM concentration. This rapid detection method can greatly shorten the detection time from several hours or even tens of hours to a few minutes, which can help to take effective measures to avoid causing large economic losses.

In Situ Collection and Rapid Detection of Pathogenic Bacteria Using a Flexible SERS Platform Combined with a Portable Raman Spectrometer.

This study aims to develop a simple, sensitive, low-cost, environmentally friendly and flexible surface-enhanced Raman scattering (SERS) platform, combined with a portable Raman spectrometer, for the rapid and on-site SERS detection of bacteria. Commercial tobacco packaging paper (TPP) with little background interference was used as a loading medium that effectively adsorbed Au nanoparticles and provided sufficient "hot spots". This Au-tobacco packaging paper (Au-TPP) substrate used as a flexible SERS platform can maximize sample collection by wiping irregular surfaces, and was successfully applied to the on-site and rapid detection of pathogenic bacteria. Raman fingerprints of pathogenic bacteria can be obtained by SERS detection of spiked pork using wipeable Au-TPP, which verifies its value in practical applications. The results collected by SERS were further verified by polymerase chain reaction (PCR) results. It showed several advantages in on-site SERS detection, including accurate discrimination, simple preparation, easy operation, good sensitivity, accuracy and reproducibility. This study indicates that the established flexible SERS platform has good practical applications in pathogenic bacterial identification and other rapid detections.

Upregulation of hsa_circ_0000977 participates in esophageal squamous cancer progression by sponging miR-874-3p.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common clinical malignancies of the digestive system, characterized by high mortality but not evident early symptoms. Molecular markers for diagnostic and outcome prediction are urgently needed. Circular RNAs might play essential roles in the progression of ESCC. METHODS: Hsa_circ_0000977 was identified using circRNA microarrays and qRT-PCR. The diagnostic value of hsa_circ_0000977 was calculated. We also examined in vitro cell functions in ECA109 and TE12 ESCC cells to determine the effect of hsa_circ_0000977. A dual-luciferase reporter vector validated the binding of hsa_circ_0000977 to miR-874-3p. RESULTS: The top 10 significantly upregulated circRNAs from microarray assays were hsa_circ_0000977, hsa_circ_0006220, hsa_circ_0043278, hsa_circ_0000691, hsa_circ_0000288, hsa_circ_0000367, hsa_circ_0021647, hsa_circ_0006440, hsa_circRNA_405571 and hsa_circRNA_100790, while the top 10 significantly downregulated circRNAs were hsa_circ_0008389, hsa_circ_0089763, hsa_circ_0089762, hsa_circ_0000102, hsa_circ_0001714, hsa_circ_0089761, hsa_circ_0007326, hsa_circ_0001549, hsa_circ_0005133 and hsa_circRNA_405965. Hsa_circ_0000977 was significantly upregulated in ESCC (p < 0.01) and had diagnostic value in ESCC. The hsa_circ_0000977 expression level was related to the pT stage and numbers of lymph nodes in ESCC patients. Elevated hsa_circ_0000977 promoted cell proliferation, migration and inhibited apoptosis in ESCC cells. Hsa_circ_0000977 might function as a micro-RNA sponge to competitively bind miR-874-3p. CONCLUSION: Disordered hsa_circ_0000977 expression can promote carcinogenesis in ESCC and might serve as a diagnostic biomarker to evaluate the occurrence and development of esophageal cancer.

BMPR2 promoter methylation and its expression in valvular heart disease complicated with pulmonary artery hypertension.

Valvular heart disease (VHD) is a common heart disease that affects blood flow. It usually requires heart surgery. Valvular heart disease complicated with pulmonary artery hypertension (VHD-PAH) may be lethal due to heart failure that results from increased heart burden. It is important for these patients to seek early treatment in order to minimize the heart damage. However, there is no reliable diagnosis method in VHD. In this study, we found DNA methylation was increased at the promoter of BMPR2 gene in the VHD patients compared with the healthy controls. This finding was confirmed by an independent cohort study of VHD patients and healthy controls. In addition, BMPR2 mRNA levels were reduced in the plasma of the VHD patients. There is strong correlation between BMPR2 promoter DNA methylation and the severity of VHD. Indeed, we found that both BMPR2 promoter DNA methylation and BMPR2 mRNA levels in the plasma are good biomarkers of VHD by themselves, with the respective AUC value of 0.879 and 0.725, respectively. When they were used in combination, the diagnostic value was even better, with the AUC value of 0.93. Consistent with the results in the VHD patients, we observed decreased BMPR2 and increased fibrosis in the lung of a PAH model mouse. BMPR2 was also decreased in the hearts of the PAH mice, whereas BMP4 was increased. Furthermore, BMPR2 was reduced in the heart valve tissue samples of human VHD patients after valve replacement with moderate/severe PAH compared with those with mild PAH. There was also increased apoptosis in the hearts of the PAH mice. BMPR2 promoter DNA methylation and its expression appear to be good biomarkers for VHD. Our results also suggest that DNA methylation may cause PAH through deregulation of BMP signaling and increased apoptosis.

Clinical characteristics and gene mutation analysis of clear cell tumor of the lung.

There were rare clinical reports on clear cell tumor of the lung (CCTL). The clinical characteristics and underlying genetic mutation status of CCTL are poorly understood. From 2012 to 2017, patients pathologically diagnosed with CCTL in our hospital were investigated and analyzed based on clinical manifestations, pathological characteristics, prognosis and full gene mutation status through next generation sequencing (NGS) technology. During a 6-year period, four eligible patients were diagnosed with CCTL through surgical resection and were included in this study. All patients showed solitary nodules or lumps located in the left lung. The average maximum diameter of lesions was 2.5 ± 1.1 cm. Computed tomography (CT) imaging characteristics of these nodules/lumps demonstrated the features of benign tumors. The hematoxylin-eosin (HE) morphology and immunohistochemistry were consistent with the histopathological features of benign CCTL. Subsequent NGS analysis showed frame shift mutations of F2421/E2419, K1466E mutation, and p. 1450_1456 deletion mutation in mTOR gene in two of four patient samples and amplifications of MCL1 were observed in three of four samples. CCTL is a rare type of primary pulmonary mesenchymal tumor with good prognosis. Preliminary diagnosis on CT is usually sclerosing pneumocytoma. It is still unclear whether the occurrence and development of the disease are related to specific gene mutation. In this study, the genomic findings of frame shift mutation of mTOR genes and amplification of MCL1 gene in CCTL suggest that these mutations might play a role in proliferation of CCTL.

[Repair of distal phalanx finger wound with modified great toe fibular flap with distal artery pedicle as reflux vein].

OBJECTIVE: To investigate the effectiveness of the modified great toe fibular flap using the distal artery pedicle as reflux vein for repairing distal phalanx finger wound. METHODS: Between June 2018 and January 2020, 15 patients who suffered tissue defect of the distal phalanx finger were treated, including 12 males and 3 females, the average age was 40.2 years (range, 24-56 years). All of them were caused by machine crush injury. There were 2 cases of thumb, 6 cases of index finger, 3 cases of middle finger, 3 cases of ring finger, and 1 case of little finger. The defects ranged from 1.7 cm×1.3 cm to 3.0 cm×2.0 cm. The time from injury to admission was 0.6-4 hours, with an average of 2.3 hours. The medial fibular proper digital artery was further dissociated to the distal end and anastomosed with the recipient vein as the reflux vein. The area of flaps ranged from 2.0 cm×1.5 cm to 3.2 cm×2.2 cm. RESULTS: All the flaps survived without vascular crisis, and the wounds healed by first intention. Except for 1 case that the suture was too tight, the incision was partially split after the stitches were removed, and it healed spontaneously after dressing change, the other patients had good healing of the donor site incision and normal foot function. All 15 patients were followed up 3-18 months, with an average of 9.3 months. The appearance of finger pulps were satisfactory with full and threaded. The color, texture, and elasticity of the flaps were good, and the two-point discrimination was 6-8 mm at last follow-up. The flexion and extension of fingers were normal. At last follow-up, hand function was evaluated according to the upper limb function evaluation trial standard of the Chinese Medical Association Hand Surgery Society, and the results were 13 cases of excellent and 2 cases of good. CONCLUSION: Modified great toe fibular flap using the distal arterial pedicle as a reflux vein can improve the venous drainage of the flap and contribute to increase the success rate of the flap without additional injury.

Rapid and label-free identification of different cancer types based on surface-enhanced Raman scattering profiles and multivariate statistical analysis.

Rapid detection and classification of cancer cells with label-free and non-destructive methods are helpful for rapid screening of cancer patients in clinical settings. Here, surface-enhanced Raman scattering (SERS) was used for rapid, unlabeled, and non-destructive detection of seven different cell types, including human cancer cells and non-tumorous cells. Au nanoparticles were used as enhanced substrates and directly added to cell surfaces. The single cellular SERS signals could be easily and stably collected in several minutes, and the cells maintained structural integrity over one hour. Different types of cells had unique Raman phenotypes. By applying multivariate statistical analysis to the Raman phenotypes, the cancer cells and non-tumorous cells were accurately identified. The high sensitivity enabled this method to discriminate subtle molecular changes in different cell types, and the accuracy reached 81.2% with principal components analysis and linear discriminant analysis. The technique provided a rapid, unlabeled, and non-destructive method for the detection and identification of various cancer types.

miRNA-1183-targeted regulation of Bcl-2 contributes to the pathogenesis of rheumatic heart disease.

To determine whether up-regulation of miR-1183 targeting the gene for anti-apoptotic factor, B-cell lymphoma 2 (BCL-2) contributes to apoptosis in patients with rheumatic heart disease (RHD). Peripheral blood samples were isolated for miR-1183 characterization. The function of miRNA-1183 in RHD using miRNA mimic on PBMCs and THP-1 cell models. The binding of miR-1183 and Bcl-2 gene was confirmed by luciferase activity test. We also measured expression levels of BCL-2 in heart valve tissue from patients with RHD using ELISA and immunohistochemistry. In silico analysis and reporter gene assays indicated that miR-1183 directly targets the mRNA encoding BCL-2. It is found that miR-1183 binds directly to the 3'UTR of the BCL-2 mRNA and down-regulates the mRNA and protein levels of BCL-2. Overexpression of miR-1183 in RHD patients and cell lines down-regulated BCL-2 expression and induced apoptosis. With the progression of the disease, the expression of BCL-2 in the heart valve tissue of patients with RHD decreased. MiRNA-1183 is up-regulated in RHD and induces cardiac myocyte apoptosis through direct targeting and suppression of BCL-2, both of which might play important roles in RHD pathogenesis. During the compensatory period of RHD, up-regulated miR-1183 destroyed the balance of apoptosis proteins (Bax and BAK) in Bcl-2 family, enhance the apoptosis cascade reaction and reduce the anti apoptosis effect. The significantly higher expression levels of miR-1183 appear to play distinct roles in RHD pathogenesis by regulation BCL-2, possibly affecting myocardial apoptosis and remodeling in the context of RHD.

Saikosaponin D inhibits proliferation and induces apoptosis of non-small cell lung cancer cells by inhibiting the STAT3 pathway.

OBJECTIVE: To study the effects of saikosaponin D (SSD) on proliferation and apoptosis in human non-small cell lung cancer cell lines, and to explore underlying mechanisms. METHODS: Following treatment with saikosaponin D, A549 and H1299 cells were assessed for anti-proliferation effects using cell cycle kit-8 assays, changes in nuclear morphology using 4',6-diamidino-2-phenylindole (DAPI) staining, and cell apoptosis using annexin V/propidium iodide double staining. Proliferation- and apoptosis-related proteins were detected by immunoblotting. RESULTS: Saikosaponin D had dose-dependent inhibitory effects on A549 cells (IC50, 3.57 µM) and H1299 cells (IC50, 8.46 µM). DAPI staining revealed decreased cell numbers, and most H1299 cells became round after treatment with 20 µM saikosaponin D. As saikosaponin D concentration increased, the proportions of cells in G0/G1 phase, and cells undergoing apoptosis, increased. Levels of phosphorylated p44/42 and signal transducer and activator of transcription (STAT)3 were significantly downregulated in both cell lines, while total STAT3 levels were not significantly affected. The cleaved form of caspase 3 was significantly upregulated. CONCLUSIONS: Saikosaponin D inhibits proliferation, inducing cell cycle arrest and apoptosis, in lung cancer cells in a dose-dependent manner, possibly through inhibition of STAT3 phosphorylation and activation of caspase 3.

Free superficial circumflex iliac artery perforator flap with a single-pedicle bilobed design for pediatric multi-digit defect reconstruction.

OBJECTIVES: This paper describes imaging and anatomical features, in order to assess the feasibility of superficial circumflex iliac artery perforator (SCIP) flap with a single-pedicle bilobed design for multi-digit skin and soft tissue reconstruction in pediatric patients. METHODS: A total of 7 pediatric patients who were being treated with free single-pedicle bilobed SCIP flap reconstruction for multi-digit defects were included in this study. The details of the clinical features were collected, and the following were successively analyzed: the preoperative computed tomographic angiography (CTA) and color Doppler sonography (CDS) examinations for flap design, the intraoperative anatomy for perforator vessel, defect reconstruction and interphalangeal range of motion (ROM) and tactile sense, pain sense, and two-point discrimination recovery results. RESULTS: CTA and CDS performed preoperatively could accurately and rapidly identify the position, location and course of the superficial circumflex iliac artery perforator. All wounds healed by the first follow-up and no complications occurred at the follow-up visit. All flaps survived, the patients achieved proximal interphalangeal joint (PIP) ranges of motions (ROM) from 80 to 100° and distal interphalangeal joint (DIP) ROM from 65 to 80°. The tactile sense and pain sense recovered, and average of the two-point discrimination scores was 9.3 mm (range 7-12 mm). The donor area was primarily sutured with a tidy scar in the underwear region. CONCLUSION: CTA and CDS performed preoperatively are accurate and intuitive methods for assessing the location and course of SCIP. The SCIP flap is suitable for pediatric patients due to its small vessel caliber, specific functional and esthetic benefits. It can be designed in a lobulated fashion in order to repair two or more wounds during one surgery. We suggest that the free single-pedicle bilobed SCIP flap should be considered a good option choice for multi-digit defect reconstruction in pediatric patients in the clinic.

Label-Free Exosomal Detection and Classification in Rapid Discriminating Different Cancer Types Based on Specific Raman Phenotypes and Multivariate Statistical Analysis.

Exosomes contain different functional bimolecular characteristics related to physiological or pathological processes and are now recognized as new biomarkers in different human cancers. Rapid detection and classification of cancer-related exosomes might be helpful in the rapid screening of patients that may have cancer. Here, we report a surface enhanced Raman scattering technology for rapid and label-free exosomal detection (Exo-SERS) to aid in the discrimination of different cancer cells based on specific Raman phenotypes and multivariate statistical analysis. The results demonstrated that exosomes derived from both tumor cells and normal cells exhibit special, unique Raman phenotypes. Using the Exo-SERS method, the cancer cells were accurately discriminated from normal cells, and subtle molecular changes between the different cell types could be detected with high sensitive. This research provides a rapid, label-free and non-destructive manner for detecting and discriminating between cancer types.

MicroRNA-9 Enhanced Cisplatin Sensitivity in Nonsmall Cell Lung Cancer Cells by Regulating Eukaryotic Translation Initiation Factor 5A2.

We determined the role of microRNA (miR)-9 in regulating cisplatin chemoresistance in nonsmall cell lung cancer (NSCLC) cells. miR-9 and eukaryotic translation initiation factor 5A2 (eIF5A2) levels were examined by reverse transcription-quantitative PCR. Cell Counting Kit-8 and the 5-ethynyl-2'-deoxyuridine (EdU) assay were used to determine the effects of miR-9 mimic or inhibitor on NSCLC cell proliferation and viability, respectively. Bioinformatics was used to analyze the relationship between miR-9 and eIF5A2. Flow cytometry was used to analyze the percentage of apoptotic cells. miR-9 mimic enhanced cisplatin sensitivity, while miR-9 inhibitor produced the opposite result. eIF5A2 was identified as a potential target of miR-9, where miR-9 regulated eIF5A2 expression at mRNA and protein level. miR-9 mimic decreased the expression of eIF5A2 mRNA and protein, while miR-9 inhibitor increased eIF5A2 expression. eIF5A2 knockdown resolved the effects of miR-9 mimic or inhibitor on cisplatin sensitivity. miR-9 may be a potential biomarker for enhancing cisplatin sensitivity by regulating eIF5A2 in NSCLC cells.

Fatal interstitial lung disease associated with Crizotinib pathologically confirmed by percutaneous lung biopsy in a patient with ROS1-rearranged advanced non-small-cell lung cancer: a case report.

BACKGROUND: Crizotinib is a multi-target inhibitor approved for the treatment of advanced non-small-cell lung cancer patients with a ROS1 rearrangement. However, interstitial lung disease is a rare but severe and fatal side effect of crizotinib that should lead to immediate discontinuation of the drug. Unfortunately, the pathophysiology, molecular mechanism and risk factors for crizotinib-induced interstitial lung disease remain poorly understood. CASE PRESENTATION: We first identified and reported interstitial lung disease induced de novo by crizotinib in a 47-year-old female patient who was diagnosed with advanced lung adenocarcinoma with a ROS1 rearrangement in a malignant pleural effusion. Subsequent next-generation sequencing analysis revealed both ROS1 rearrangement and an EGFR exon 19 deletion mutation in lung biopsy specimens, which were histologically confirmed to be interstitial lung disease. Although crizotinib treatment was ceased immediately and a shock treatment with high-dose methylprednisolone as well as other necessary treatment procedures was applied to reverse the interstitial lung disease process, the patient died. CONCLUSIONS: The present case indicates that while treating non-small-cell lung cancer patients with crizotinib, it is important to constantly monitor any newly emerging respiratory symptoms and unexplained imaging changes, which may suggest an adverse effect related to drug-induced interstitial lung disease or even lethality. Histopathology and molecular pathological examination of lung biopsy specimens may help clinicians understand the development mechanism and exclude other causes.

Correction: Local thoracic therapy improve prognosis for stage IV non-small cell lung cancer patients combined with chemotherapy: A Surveillance, Epidemiology, and End Results database analysis.

[This corrects the article DOI: 10.1371/journal.pone.0187350.].