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The response to icotinib in advanced non‐small cell lung cancers (NSCLC) with EGFR uncommon mutation (EGFRum) is unclear. Here we reported the efficacy and potential resistance mechanism of icotinib in Chinese EGFRum NSCLC patients. Between July 2013 and November 2016, 3117 NSCLC patients were screened for EGFRum in a multi‐center study in China. Circulating tumor DNA (ctDNA) was detected and analyzed using next‐generation sequencing (NGS) after progression from icotinib. The efficacy, safety and the potential resistance mechanism of icotinib were explored. After a median follow‐up of 6.2 months, 69 patients (70.41%) developed disease progression, the objective rate (ORR) and disease control rate (DCR) were 13.27% and 29.59% respectively, and the median progression‐free survival (PFS) was 5.5 months (95% CI: 1.2‐13.0 months). Both complex‐pattern with EGFR classical mutations (EGFRcm) and single‐pattern have better PFS than complex‐pattern without EGFRcm (median PFS was 7.2 (95% CI: 4.65‐9.75), 5.2 (95% CI: 3.24‐7.16) and 3.2 (95% CI: 2.97‐3.44) months, respectively, P <.05); patients harboring S768I mutation had the worst PFS than others (2.0 months, P <.05). Diarrhea was the most frequent side effect (42.9%). Forty‐eight (69.6%) patients developed drug resistance after 3.0 months and 81.2% of them acquired T790M mutation. Better response was observed in complex‐pattern with the EGFRcm group. S768I mutation carriers may not benefit from icotinib. Acquired T790M mutation was common in icotinib‐resistant EGFRum NSCLC patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this meta-analysis is to evaluate the distribution pattern of KRAS and BRAF mutations in colorectal cancer.Materials and Methods: The database was searched without language restrictions. Meta-analyses were conducted using the STATA software. We calculated the odds ratio (OR) and its 95% confidence interval (95% CI) to estimate the distribution of and correlation between KRAS and BRAF mutations, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) in left- and right-sided colorectal cancer.Results: The studies were divided into five groups: (1) distribution of KRAS/BRAF mutations in distal and proximal colorectal cancer, the summary OR value was 1.24 versus 4.03, (2) distribution of KRAS/BRAF mutations in CIMP-low/Neg and CIMP-high (CIMP-H) tumors, the summary OR value was 0.77 versus 10.49, (3) distribution of KRAS/BRAF mutations in MSI-low (MSI-L)/microsatellite stable (MSS) and MSI-high (MSI-H) tumors, the summary OR value was 0.51 versus 9.60, (4) proportion of CIMP-H/MSI-H tumors among distal and proximal colorectal tumors, the summary OR value was 3.66 versus 6.54, and (5) proportion of CIMP-H tumors among MSI-L/MSS and MSI-H tumors, the summary OR value was 5.87.Conclusion: The meta-analysis reveals that KRAS has a slightly higher mutation rate in MSI-L/MSS tumors. Moreover, BRAF mutations have higher detection rates in right-sided colorectal cancer, which suggests that BRAF mutations are likely in CIMP-H tumors. Therefore, based on these findings, the molecular diagnostic tests to be conducted in colorectal cancer patients can be determined according to the location/clinical features of the tumor. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy is the major choice for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion (EGFR ex20ins). The efficacy of pemetrexed-based with other chemotherapy regimens and EGFR ex20ins subtypes in this population has not been well studied., Methods: We screened patients with EGFR ex20ins by next-generation sequencing (NGS) from a large cohort. The clinicopathologic and medical information were collected in advanced NSCLC patients with EGFR ex20ins. We also compared the clinical outcomes among patients with different subtypes of EGFR ex20ins., Results: We retrospectively collected 119 stage IIIB/IV NSCLC patients with EGFR ex20ins from 9142 NSCLC patients across China from June 2013 to December 2018. The subtypes of EGFR ex20ins included A767&#95;V769dupASV (33/119, 27.73%), S768&#95;D770dupSVD (19/119, 15.97%), N771&#95;H773dupNPH (11/119, 9.24%), A763&#95;Y764insFQEA (2/119, 1.68%) and others (54/119, 45.38%). A total of 64.7% (77/119) of patients received pemetrexed-based first-line chemotherapy and 13.45% (16/119) of patients received pemetrexed-based second-line chemotherapy. Pemetrexed-based chemo-treated patients had longer median progression-free survival (PFS) than patients without pemetrexed-based chemo-treated (5.5 vs. 3.0 months, P=0.0026). Survival data was available for 66 patients and the median overall survival (OS) was 24.7 months. Pemetrexed-based chemo-treated patients had longer OS tendency than patients without pemetrexed-based chemo-treated (25.0 vs. 19.6 months, P=0.0769). Patients harboring A767&#95;V769dupASV had better OS than other subtypes of EGFR ex20ins but without statistical significance (P=0.0676). Multivariate analysis revealed that histological type of NSCLC and bone-metastasis before treatment were independent prognostic factors for OS in all patients after adjusting all characteristic and treatment factors (P<0.05)., Conclusions: To the best of our knowledge, it is the largest cohort study of advanced NSCLC patients with EGFR ex20ins across China. Pemetrexed-based treatment could have better control of disease than non-pemetrexed-based chemotherapies in this population. Furthermore, more effective agents are expected for patients harboring EGFR ex20ins., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-382). The authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Non-thyroid malignancies to the thyroid gland resulting from distant metastases are extremely rare, and such cases are rarely seen in clinical settings. The question of how a tumor metastasizes to the thyroid remains unanswered. Here we report a case of lung adenocarcinoma metastasizing to the thyroid gland. The article covers the pathological features, treatments, examination reports, and the postoperative follow-up reviews of the patient. In this article, we discuss the diagnostic method, the spread route, the prognosis, the mechanism and above all, the treatment. In addition, we searched the PubMed and ISI Web of Science databases for articles published in English using the key words "lung", "thyroid", and "metastasis", and we reviewed nearly all the reports about thyroid malignancies being metastasized from lung cancer. This rare case emphasizes the importance of the multifaceted comprehensiveness of the cephalometry diagnosis, pathological diagnosis, and immunohistochemical analysis to ensure that such rare cases are not missed. We declare that all cases of thyroid malignancies metastasized from the lungs shall be reported at large for further clinical research., Competing Interests: None., (IJCEP Copyright © 2019.)

Objective: To analysis the E protein epitopes of dengue virus type 1-4, Japanese encephalitis virus and yellow fever virus and to distinguish the shared or specific epitopes among them., Methods: Bioinformatic software DNAStar was used to analyze the hydrophilicity, flexibility, surface probability and antigenicity of dengue virus type 1-4, Japanese encephalitis virus and yellow fever virus E protein amino acid sequences. The influence of secondary structure was also considered. Based on the bio-informatic analysis of E protein epitopes, 6 specific epitopes were amplified and inserted into prokaryotic expression vector pMAL-c2x. The vectors was then transferred into E. coli BL21 (DE3) and Rosetta (DE3). Isopropyl-beta-D-thiogalactoside (IPTG) was used to induce the expression of gene segments and SDS-PAGE were used identify the expression proteins. The antigenicity was tested, using Western blot., Results: 15 shared epitopes and 47 specific epitopes were forecasted by bioinformatic analysis, and 6 specific epitopes from dengue virus type 1-4, Japanese encephalitis virus and yellow fever virus E protein were expressed in E. coli successfully. Two specific antigenic determinant from dengue virus type 1 and dengue virus type 2 were confirmed using Western blot, while the others epitopes shown no antigenic reaction property., Conclusion: Two specific antigenic determinant were confirmed, under Western blot.

Objective: To establish a specific, sensitive and practicable method for detection and typing of dengue virus., Methods: Based on the genomic sequence analysis of dengue virus types 1-4, 4 pairs of primers were designed. The specific capture probes of dengue virus types 1-4 were amplified using RT-PCR, cloned and sequenced before using them for precoating the microwell plate. The samples were amplified using biotin-labeled forward primer and reverse primer, and microwell plate hybridization was carried out for detection and typing of dengue virus types 1-4., Results: The absorbance of the positive samples were higher than 0.5, while the average absorbance of the negative samples was lower than 0.1, with the S/N higher than 10., Conclusion: The method of PCR-ELISA we established for early detection and typing of all 4 dengue viruses seretypes.

Objective: To develop multiplex reverse translation-polymerase chain reaction (RT-PCR) method for detection of dengue virus type 1-4., Methods: Based on the genomes sequence analysis of dengue virus type 1-4, four-pair of primers were designed. The specificity of the primers was primarily tested by searching the GenBank DNA sequence database. The optimal reaction conditions of the multiplex RT-PCR were then established. The specificity of RT-PCR was tested using the homologous yellow fever virus and Japanese encephalitis virus. 30 serum samples of dengue virus from suspected sufferers in the prevalence of dengue virus in 2003 were detected using the methods we developed., Results: Positive segments about 295, 237, 118, 347 bp could be seen in the multiplex RT-PCR production of dengue virus type 1-4, respectively. There were no positive segments in the RT-PCR productions of Japanese encephalitis virus and yellow fever virus. 25 of the 30 serum samples showed dengue virus type 1 positive results, while the sequencing results suggesting the amplification sequence having a high homology with dengue virus type 1 strain Cambodia, GD14/97 and GD05/99 (97%, 97%, 98%, respective)., Conclusion: The method of multiplex RT-PCR we established could be used for early detection and identification of dengue virus type 1-4.

Objective: To trace the infection sources of three dengue virus type 1 isolates found in Guangdong province, namely GD05/99, GD14/97 and GD23/95., Methods: According to the genomes of dengue virus type 1 S275 strain, a pair of primers was designed for amplification of the structural protein E gene of the isolated dengue virus type 1 strains by reverse transcriptase-PCR. The amplified gene fragment was then cloned into pMD18-T vector and sequenced., Results: GD14/97 and GD05/99 shared a high nucleotide homology with Cambodia (98% and 99% respectively) and may belong to the same genotype. GD23/95 had a 95% nucleotide homology with A88, higher than that with other strains. GD23\95 and A88 may belong to another genotype., Conclusion: The dengue fever outbreak in Guangdong during 1999, 1997, and 1995 may originate from the viruses from different countries.

Objective: To identify the virus isolated from Jiangmen, Guangdong province and to discuss the possible origin., Methods: Using characteristics of indirect fluorescent antibody tests (IFA), reverse transcription-polymerase chain reaction (RT-PCR), mouse neurovirulence and cell culture to identify the isolated virus. According to the nature of dengue virus type 2 NGC strain, two pairs of primers were designed. The structural protein gene of isolated dengue virus type 2 strain was then amplified by RT-PCR, cloned into pMD18-T vector and sequenced., Results: Twenty-two of 37 serum samples showed a positive reaction to dengue antibody IgG, and 36 of 37 with IgM with the highest antibody titer 1:640. Ten samples were resulted in a cytopathy on C6/36 cells and showed a neurovirulence in suckling mice when inoculated intracerebrally. The structural gene of new isolate GD19/2001 containing 2 325 nucleotides which encoded 774 amino acids. Data on nucleotide homology were 98%, 96%, 94%, 94%, 92%, 92%, 92% and 91% compared with TSV01, GD06/93, NGC and 44, ThNH81/93, 04 and GD08/98, and S1 respectively., Conclusion: The isolated virus from Jiangmen, Guangdong province belonged to dengue virus type 2, which might come from Australia.