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BackgroundMETamplification plays an important role in the development of non-small-cell lung cancer (NSCLC) either de novo or in resistance to epidermal growth factor receptor tyrosine–kinase inhibitor (EGFR-TKI) settings. Fluorescence in situ hybridization (FISH) is the standard method forMETamplification. With more and more discoveries of oncogenic driver genes, next-generation sequencing (NGS) plays a significant role in precision oncology. Meanwhile, the role of NGS inMETamplification remains uncertain.MethodsForty patients diagnosed with advanced NSCLC were included. FISH and NGS were conducted prior to MET inhibitors treatment.METamplification by FISH was defined as a MET/CEP7 ratio of > 2.0 and/or copy number (CN) > 5.METamplification by NGS was defined as gene copy number (GCN) ≥ 5.ResultsThe concordance rate among FISH and NGS was 62.5% (25/40).METamplification identified by FISH showed the optimal predictive value. The partial response (PR) rate was 68.0% (17/25 withMETamplification) vs. 6.7% (1/15 withoutMETamplification); the median progression-free survival (PFS) was 5.4 months versus 1.0 months (P METamplification identified by NGS failed to distinguish significant clinical outcomes. The PR rate was 60.0% (6/10, withMETGCN ≥ 5) vs. 40.0% (12/30, withMETGCN ConclusionsMETamplification identified by FISH remains the optimal biomarker to identify suitable candidates for MET-TKI therapy. In comparison, amplification identified by NGS seems not as robust to be effective predictive biomarker. Further exploration is needed regarding the focal amplification by NGS in predicting the efficacy.

BACKGROUND Computed tomography (CT) and magnetic resonance imaging (MRI) are both capable of predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). However, which modality is better is unknown. PURPOSE To intraindividually compare CT and MRI for predicting MVI in solitary HCC and investigate the added value of radiomics analyses. STUDY TYPE Retrospective. SUBJECTS Included were 402 consecutive patients with HCC (training set:validation set = 300:102). FIELD STRENGTH/SEQUENCE T2-weighted, diffusion-weighted, and contrast-enhanced T1-weighted imaging MRI at 3.0T and contrast-enhanced CT. ASSESSMENT CT- and MR-based radiomics signatures (RS) were constructed using the least absolute shrinkage and selection operator regression. CT- and MR-based radiologic (R) and radiologic-radiomics (RR) models were developed by univariate and multivariate logistic regression. The performance of the RS/models was compared between two modalities. To investigate the added value of RS, the performance of the R models was compared with the RR models in HCC of all sizes and 2-5 cm in size. STATISTICAL TESTS Model performance was quantified by the area under the receiver operating characteristic curve (AUC) and compared using the Delong test. RESULTS Histopathologic MVI was identified in 161 patients (training set:validation set = 130:31). MRI-based RS/models tended to have a marginally higher AUC than CT-based RS/models (AUCs of CT vs. MRI, P: RS, 0.801 vs. 0.804, 0.96; R model, 0.809 vs. 0.832, 0.09; RR model, 0.835 vs. 0.872, 0.54). The improvement of RR models over R models in all sizes was not significant (P = 0.21 at CT and 0.09 at MRI), whereas the improvement in 2-5 cm was significant at MRI (P

Background Here we present a rare case of localized amyloidosis involving the nasolacrimal duct and lacrimal sac which was managed by endoscopic surgery. Case summary A 50-year-old man whose medical history included bilateral ventricular fold and vocal cord amyloidosis complained of bilateral epiphora. Magnetic resonance imaging revealed a neoplasm within the nasolacrimal sac. Characteristic positivity for Congo red staining and birefringence under a polarized microscope proved the diagnosis of amyloidosis. Dacryocystorhinostomy via an endoscope obtained a favorable result. A one-year follow-up found no recurrence. Conclusion There are few reports on amyloidosis involving the lacrimal outflow system, and management and outcome are not clear. Endoscopic dacryocystorhinostomy can be a choice to relieve symptoms. Regular follow-up and monitoring of systemic diseases are highly recommended.

The self-crosslinked hyaluronic acid (scHA) and steroids are considered as efficient factors for postoperative management after chronic rhinosinusitis (CRS) nasal surgery. This randomized clinical trial is designed to investigate the efficacy and potential of scHA gel as a topical drug sustained release carrier for steroid of budesonide. The study is performed with 30 patients of chronic rhinosinusitis with nasal polyps (CRSwNP) who underwent functional endoscopic sinus surgery (FESS). The single application of scHA was assessed in the control patient group for postoperative recovery. In the treatment patient group, the combination of scHA/budesonide was applied for postoperative management. The patients are followed up in 2 weeks, 4 weeks and 12 weeks after surgery. The combination of scHA/budesonide results in better endoscopic scoring and mucus evaluation than the single scHA application. The results indicate that the combination of scHA/budesonide is a valuable treatment for the FESS postoperative management and implies the potential of scHA gel as a topical drug sustained release scaffold.

Background In previous studies, the predictive role of BIM deletion polymorphism with respect to responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) has been controversial. The potential reasons for these inconsistent findings were unknown. Methods Data from CTONG0901 clinical trial and medical records of Guangdong Lung Cancer Institute (GLCI) were retrospectively pooled. A total of 194 and 141 EGFR‐mutant non‐small cell lung cancer (NSCLC) patients treated with first‐ and second‐generation EGFR‐TKIs were examined in the CTONG0901 and GLCI cohorts, respectively. Sixty‐eight patients were treated with third‐generation EGFR‐TKIs in the GLCI cohort. The BIM gene status was examined by next‐generation sequencing. Results The frequency of BIM deletion polymorphism was 11.3% and 17.0% in CTONG0901 and GLCI cohorts, respectively. For first‐ and second‐generation EGFR‐TKIs in CTONG0901 cohort, objective response (ORR) was 54.5% in BIM deletion group versus 56.4% in wild‐type BIM group (P = .87); disease control rate (DCR) was 90.9% versus 88.4% (P = 1.00); progression‐free survival (PFS) was 10.5 versus 11.2 months (P = .59); and overall survival (OS) was 20.5 versus 20.5 months (P = .73). In GLCI cohort, ORR was 54.2% versus 60.7% (P = .55); DCR was 91.7% versus 96.6% (P = .27); PFS was 10.1 versus 11.6 months (P = .63); and OS was 58.5 versus 45.0 months (P = .93). For third‐generation EGFR‐TKIs, ORR was 18.2% versus 63.2% (P = .02); DCR was 81.8% versus 96.5%, (P = .12); PFS was 5.8 versus 9.0 months (P = .13); and OS was 30.0 versus 24.8 months (P = .85). Cox regression analysis showed that concomitant genetic alterations could adversely affect the response to EGFR‐TKIs, but not BIM deletion. Conclusions The presence of BIM deletion showed no relation to an impaired response to first‐, second‐, and third‐generation EGFR‐TKIs in NSCLC patients. The factors influencing the response of EGFR‐TKIs were concomitant genetic alterations, but not BIM deletion.

Introduction: Lung cancer is the most prevalent malignant tumors worldwide. Over the past decade, the emergence of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has ushered in a new era of lung cancer treatment. Therefore, clinical trials investigating the efficacy and safety of these drugs are important.Areas covered: This review provides an overview on the safety of three classes of EGFR-TKIs and discusses the adverse events (AEs) and reactions reported in the literature.Expert opinion: EGFR-TKIs significantly improve progression-free survival and overall survival in non-small cell lung cancer (NSCLC) patients with an activating mutation of EGFR. However, EGFR-TKIs also block the EGFR-regulating pathways in the skin and gastrointestinal tract and cause AEs, including diarrhea, liver toxicity, skin disease, stomatitis, interstitial lung disease, and ocular toxicity, which have detrimental effects on quality of life and drug compliance. Clinicians should understand how to prevent and control these adverse reactions, which can often be achieved by dose reduction, discontinuation of treatment, or switching to another drug.

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide. Checkpoint blockade immunotherapy has made tremendous progress in the treatment of a variety of cancers in recent years. Costimulatory molecules constitute the foundation of cancer immunotherapies and are deemed to be promising targets for cancer treatment. This study attempted to evaluate the potential value of costimulatory molecule genes (CMGs) in HNSCC.Materials and MethodsBased on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, we identified the prognostic value of CMGs in HNSCC. Subsequently, CMGs-based signature (CMS) to predict overall survival of HNSCC patients was established and validated. The differences of downstream pathways, clinical outcomes, immune cell infiltration, and predictive immunotherapy responses between different CMS subgroups were investigated via bioinformatic algorithms. We also explored the biological functions of TNFRSF12A, one risk factor of CMS, by in vitro experiments.ResultsAmong CMGs, 22 genes were related to prognosis based on clinical survival time in HNSCC. Nine prognosis-related CMGs were selected to establish CMS. CMS was an independent risk factor and could indicate the survival of HNSCC patients, the component of tumor-infiltrating lymphocytes, and the immunotherapy response rate. Functional enrichment analysis confirmed that CMS might involve immune-relevant processes. Additionally, TNFRSF12A was related to poor prognosis and enhanced malignant phenotype of HNSCC.ConclusionCollectively, CMS could accurately indicate prognosis, evaluate the tumor immune microenvironment, and predict possible immunotherapy outcomes for HNSCC patients.

Background and Purpose: Ipsilateral thalamic diaschisis (ITD) initially describes functional depression of the thalamus ipsilateral to a supratentorial lesion, but accumulating evidence has shown morphological changes also occur. Therefore, we aimed to characterize thalamic perfusion and diffusion related to ITD over time and their inter-relationships after middle cerebral artery infarction. Methods: Eighty-five patients with middle cerebral artery infarction who underwent diffusion kurtosis imaging and arterial spin labeling were retrospectively included. ITD was diagnosed as ipsilateral thalamic hypoperfusion present on ≥2 cerebral blood flow maps. The thalamic asymmetrical index was calculated as (ipsilateral value−contralateral value)/contralateral value×100%. Finally, the inter-relationships of thalamic perfusion and diffusion were analyzed. Results: ITD was present in 56/85 patients (65.9%, ITD+). In ITD+ patients, larger abnormal perfusion volume, higher perfusion-infarct mismatch and lower rates of focal hyperperfusion were observed than ITD− patients. Infarction affecting the corona radiata were more frequent among ITD+ patients. Mean kurtosis were slightly but significantly increased within the ipsilateral thalamus compared with the contralateral one in ITD+ patients of subacute and chronic groups, while fractional anisotropy was significantly increased in subacute group but decreased in chronic group for both ITD+ and ITD− patients. Mean diffusivity was significantly increased in ITD+ patients of chronic group. Furthermore, the AI CBF was negatively and significantly correlated with AI MK and AI FA in ITD+ patients in subacute group, and AI MD , even after adjustment for abnormal perfusion volume and days from symptoms onset, in chronic group. ITD+ patients had significantly higher National Institutes of Health Stroke Scale and modified Rankin Scale scores at admission and discharge and also showed a trend to independent association with clinical outcome at discharge. Conclusions: The combination of arterial spin labeling and diffusion kurtosis imaging can reveal early, time-specific thalamic perfusion and diffusion changes after middle cerebral artery infarction. ITD-related hypoperfusion was significantly correlated with underlying microstructural alterations.

The ectoparasitoid beetle, Dastarcus helophoroides (Fairmaire) (Coleoptera: Bothrideridae), has been widely used as a biological control agent for many cerambycid beetles in China, Korea, and Japan. However, much less is known about its phototactic behavior to visual stimuli. In this paper, the phototactic behavioral response of D. helophoroides to 27 monochromatic lights and to nine illumination intensities of the most attractive light was evaluated using light-emitting diodes (LEDs) as light sources. The results showed that in dual choice between darkness and individual LED light, D. helophoroides adults exhibited a positively phototactic response to all wavelengths ranging from 300 to 860 nm. The near-infrared light (NIR, ranging from 700 to 760 nm) elicited stronger phototactic behavioral response, showing a preference for NIR wavelengths light. In paired choice among four preferred NIR lights, D. helophoroides adults displayed a significantly more favorable response to NIR light at 700 nm. Furthermore, the beetles expressed varying levels of sensitivity to illumination intensities from 1 to 600 lux under NIR light at 700 nm. The phototactic response was strongest at 7 lux and a statistically significant downward trend was found with increasing or decreasing the illumination intensities. These findings clearly demonstrate that D. helophoroides is a positively phototactic insect and its phototactic behavior is significantly influenced by light wavelength and illumination intensity, among which NIR light with peak wavelength at 700 nm and an intensity at 7 lux are most suitable in attracting D. helophoroides adults.

Background Olfactory neuroblastoma (ONB) is a rare malignancy arising in the nasal vault. Endoscopic resection has been reported to improve overall survival (OS). At present, clinicopathological predictors of the prognosis of ONB remain undefined. Methods Data including demographics, clinical characteristics and follow-up information of ONB patients treated with endoscopic surgery were collected. Risk factors on OS rates were investigated by LASSO and Cox analyses. A nomogram was developed and evaluated with internal validation. Risk groups were established according to patients’ points in the nomogram. Findings 154 ONB patients treated with surgery were included in this single center study. A nomogram based on multivariate Cox regression model including multiple tumor history, orbital invasion, carotid canal invasion, modified Kadish stage, delivery sequence of RT and surgery, sequence of chemotherapy and surgery was developed. The bias-corrected C-index (0.886 [95% CI: 0.843-0.943]) was significantly higher than of conventional staging classifications. The AUC of nomogram regarding 1-, 2- and 5-year OS probabilities reached 0.912, 0.929 and 0.957, respectively. The risk levels based on nomogram points were more discriminative than conventional classifications. Interpretation Validation analysis showed good predictive accuracy and discriminative ability of the nomogram. Therefore, the nomogram could be utilized to individually predict survival probability for ONB patients after endoscopic resection. Funding This study was funded by the Chinese Academy of Medical Sciences (No. 2019-I2M-5-003), the Shanghai Science and Technology Commission (No. 19411950600), the Shanghai Hospital Development Center (No. SHDC12018118) and the Eye, Ear, Nose and Throat Hospital of Fudan University (No. SYB202006).

Background The KRAS mutation is the second most common genetic variant in Chinese non-small cell lung cancer (NSCLC) patients. At the 2019th World Conference of Lung Cancer, the KRAS G12C-specific inhibitor AMG510 showed promising results in the phase I clinical trial. However, the frequency, clinical characteristics, and prognostic significance of the KRAS G12C mutation in Chinese NSCLC patients are rarely reported. Methods Next-generation sequencing was used to confirm the KRAS mutation status in 40,804 NSCLC patients from multiple centers (mCohort). Survival data were collected retrospectively from 1456 patients at one of the centers, the Guangdong Lung Cancer Institute (iCohort). Results In the mCohort, 3998 patients (9.8%) were confirmed to harbor a KRAS mutation, of whom 1179 (29.5%) had the G12C subtype. In the iCohort, 130 NSCLC patients (8.9%) had a KRAS mutation and 42 (32.3%) had the G12C subtype. The G12C subgroup included more male patients (85.2% vs 67.4%, P P = 0.02) than did the non-G12C subgroup. Both the KRAS mutation group and KRAS G12C mutation subgroup were associated with a shorter median overall survival (OS) than wildtype tumors (15.1 vs 26.7 months, hazard ratio [HR]KRAS = 1.50, P = 0.002; 18.3 vs 26.7 months, HRG12C = 1.66, P = 0.007). In Cox regression analysis, smoking (HR = 1.39, P = 0.05) and stage IV disease (HR = 2.72, P KRAS mutation (HR = 1.30, P = 0.07) and KRAS G12C mutation (HR = 1.47, P = 0.07) reached borderline significance. Conclusions In the largest sample used thus for, our study found that approximately 10% of Chinese NSCLC patients had KRAS mutations. Of these, nearly 30% harbored the KRAS G12C mutation subtype, which was most common in male smokers. The KRAS G12C mutation is a biomarker of poor prognosis in Chinese NSCLC patients, which could potentially be improved by G12C-specific inhibitors in the future. (296 words)

Highlights • Predictive power of PD response for ICIs was superior than traditional biomarkers; • Predictive efficacy was improved by integrating tumor-immune-related features; • When tumor-specific feature was replaced, the model has pan-cancer applicability. • NRAS and PDPK1 have the potential to induce primary resistance to ICIs., Background Treatment by immune checkpoint blockade (ICB) provides a remarkable survival benefit for multiple cancer types. However, disease aggravation occurs in a proportion of patients after the first couple of treatment cycles. Methods RNA sequencing data was retrospectively collected. 6 tumour-immune related features were extracted and combined to build a lung cancer-specific predictive model to distinguish responses as progression disease (PD) or non-PD. This model was trained by 3 public pan-cancer datasets and a lung cancer cohort from our institute, and generated a lung cancer-specific integrated gene expression score, which we call LITES. It was finally tested in another lung cancer dataset. Results LITES is a promising predictor for checkpoint blockade (area under the curve [AUC]=0.86), superior to traditional biomarkers. It is independent of PD-L1 expression and tumour mutation burden. The sensitivity and specificity of LITES was 85.7% and 70.6%, respectively. Progression free survival (PFS) was longer in high-score group than in low-score group (median PFS: 6.0 vs. 2.4 months, hazard ratio=0.45, P=0.01). The mean AUC of 6 features was 0.70 (range=0.61-0.75), lower than in LITES, indicating that the combination of features had synergistic effects. Among the genes identified in the features, patients with high expression of NRAS and PDPK1 tended to have a PD response (P=0.001 and 0.01, respectively). Our model also functioned well for patients with advanced melanoma and was specific for ICB therapy. Conclusions LITES is a promising biomarker for predicting an impaired response in lung cancer patients and for clarifying the biological mechanism underlying ICB therapy.

Renal function varies according to the nature and stage of diseases. Renal functional magnetic resonance imaging (fMRI), a technique considered superior to the most common method used to estimate the glomerular filtration rate, allows for noninvasive, accurate measurements of renal structures and functions in both animals and humans. It has become increasingly prevalent in research and clinical applications. In recent years, renal fMRI has developed rapidly with progress in MRI hardware and emerging postprocessing algorithms. Function-related imaging markers can be acquired via renal fMRI, encompassing water molecular diffusion, perfusion, and oxygenation. This review focuses on the progression and challenges of the main renal fMRI methods, including dynamic contrast-enhanced MRI, blood oxygen level-dependent MRI, diffusion-weighted imaging, diffusion tensor imaging, arterial spin labeling, fat fraction imaging, and their recent clinical applications. Level of evidence 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:863-881.

Background Although TP53 co-mutation with KRAS/ATM/EGFR/STK11 have been proved to have predictive value for response to immune checkpoint inhibitors (ICIs), not all TP53 mutations are equal in this context. As the main part of TP53 mutant types, Missense and Nonsense alternations in TP53 as independent factors to predict the response to ICIs within Lung Adenocarcinoma (LUAD) patients have not yet been reported. Methods An integrated analysis based on multiple-dimensional data types including genomic, transcriptomic, proteomic and clinical data from published lung adenocarcinoma data and local database of LUAD taking immune checkpoint inhibitors. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups. Single-sample GSEA (GSVA) is conducted to calculate the score for enrichment of a set of genes regulating DNA damage repair (DDR) pathway. Findings The TP53-missense-mutation group showed increased PD-L1 (CD274) level and enriched IFN-γ signatures compared with the TP53-wild-type subgroup, but no differences were noted in patients with nonsense-mutant vs wild-type p53. Furthermore, a group of suppressor Immune cells like M2 Macrophage and Neutrophils are found enriched in nonsense group. On the other-side, both TP53 missense and nonsense mutations are associated with elevated TMB and neoantigen levels and contribute equally to DNA damage repair deficiency. The distribution regarding to multi-dimensional factors determining the efficacy of ICIs finally transformed into diverse clinical benefits for LUAD. TP53 missense but not -nonsense Mutants are associated with better clinical benefits taking antiPD-1/1L. However, all such TP53 subgroups responds well to nivolumab (antiPD-L1) plus ipilimumab (antiCTLA-4) therapy. Interpretation Our study demonstrated that not all TP53 mutations are equal in predicting efficacy in patients with LUAD treated with ICIs. Multi-center data showed that TP53 missense and nonsense mutations were significantly different in terms of associations with PD-L1 expression, IFN-γ signatures and TME composition. Special attention should be paid to potential TP53 mutation heterogeneity when evaluating TP53 status as biomarker for ICIs. Funding The study was supported by Key Lab System Project of Guangdong Science and Technology Department – Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120, to Yi-Long WU)

The proportion of aged population nowadays almost rises acutely in each countries, which resulted from the increasing life expectancy and falling fertility rates. The impairment of mobility is a major health concern for the elderly. While the more decline of daily activities, more dangerous the elderly would be. The design of an image-based surveillance system for tracking elderly's activities in home was proposed in this paper, and the algorithm of shadow elimination was applied to reduce the effect of the subject's shadow for regional segmentation. The HOG-SVM algorithm-based image segmentation technique was recommended to analyze the gradient orientations of segmented objects to follow the trail of the subject movement. The accuracy of this method is almost 96.3%. We hope this designed construction system can be applied in the clinical application for the elderly in the respects of health care and home care in the future.

Objective To investigate ultrastructural changes in pulmonary tissue of a rat model of pulmonary fibrosis following treatment with compound Carapax trionycis ( C. trionycis ; Biejia in Chinese) formula. Methods Sixty male Sprague-Dawley rats were randomly divided into four groups ( n =15): compound C. trionycis formula high-, middle-, and low-dose groups as well as model group. Pulmonary fibrosis was induced by bleomycin. Five rats from each group were sacrificed on day 7, 14 and 28 of the drug treatment, respectively. The pulmonary tissue was harvested followed by hematoxylin-eosin staining and subsequent transmission electron microscopy. The Szapiel's method was used to assess the degree of alveolitis and pulmonary fibrosis. Results Compared with the model group, the compound C. trionycis formula groups had slighter pulmonary alveolitis after the 7-day treatment and also had alleviated alveolar inflammation and pulmonary fibrosis after the 14-day treatment. After the 28-day treatment, the compound C. trionycis formula groups showed deposition of a small amount of fibrous tissue and lesions occupying less than 21% of the whole lung area, while the model group showed focal or diffuse fibrous deposition, narrow alveolar cavity, disordered lung structure, and lesions in larger than 51% of the whole lung area. Conclusions The compound C. trionycis formula can inhibit the proliferation of collagen fibers and resist pulmonary fibrosis.