EGFR L792H and G796R: Two Novel Mutations Mediating Resistance to the Third-Generation EGFR Tyrosine Kinase Inhibitor Osimertinib.

Background: The third-generation EGFR tyrosine kinase inhibitor osimertinib has been approved in many countries to treat advanced NSCLC in patients with the EGFR T790M mutation. As the development of acquired resistance is inevitable, it is urgent that the mechanisms of such resistance be clarified.

Methods: DNA samples from a cohort of 340 patients with lung adenocarcinoma who were taking osimertinib were subjected to next-generation sequencing and screened in terms of the frequencies of the L792H and G796R mutations.

ADAURA: Phase III, Double-blind, Randomized Study of Osimertinib Versus Placebo in EGFR Mutation-positive Early-stage NSCLC After Complete Surgical Resection.

Introduction: Currently, the role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as adjuvant therapy for early-stage non-small-cell lung cancer after complete surgical tumor resection remains under investigation. We present the rationale and study design for the ADAURA (ClinicalTrials.gov identifier, NCT02511106) trial, a multicenter, double-blind, randomized, placebo-controlled study.

[Detection of differentially expressed gene of allergic rhinitis based on RT² profiler PCR array].

The aim of this study is to detect differentially expressed gene of allergic rhinitis (AR) based on RT² profiler PCR array. The real-time PCR array containing 84 genes were used to compare inferior turbinate samples obtained from AR patients (n=8) and healthy individuals (n=8). The results showed that 67 genes were down regulated and 17 genes were up regulated in AR inferior turbinate after analysis of 84 genes related to allergy and asthma.

Final Overall Survival Analysis From a Study Comparing First-Line Crizotinib Versus Chemotherapy in ALK-Mutation-Positive Non-Small-Cell Lung Cancer.

Purpose The phase III PROFILE 1014 trial compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) -positive advanced nonsquamous non-small-cell lung cancer. Here, we report the final overall survival (OS) results. Patients and Methods Patients were randomly assigned to receive oral crizotinib 250 mg twice daily (n = 172) or intravenous pemetrexed 500 mg/m plus cisplatin 75 mg/m or carboplatin (area under the concentration-time curve of 5 to 6 mg·mL/min) every 3 weeks for a maximum of six cycles (n = 171).

Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-tumour Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis.

Background And Aims: The association between anti-tumour necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumour necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients.

"Hepatic Superscan" in a Patient With Hepatosplenic Alphabeta T-cell Lymphoma: 18F-FDG PET/CT Findings.

A 36-year-old woman with a 2-week history of fever and markedly elevated lactate dehydrogenase levels. Nonenhanced CT and contrast-enhanced CT showed hepatosplenomegaly, diffusely decreased attenuation of the liver, and homogeneous enhancement in the hepatic and splenic parenchyma. F-FDG PET/CT revealed diffuse intense heterogeneous uptake by the liver (like superscan in bone scintigraphy).

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

Background: EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear.

VISTA expression associated with CD8 confers a favorable immune microenvironment and better overall survival in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) often arises in the setting of chronic inflammation with multiple inhibitory immune signals. V-domain Ig suppressor of T cell activation (VISTA) is identified as a novel negative checkpoint regulator. This study sought to determine the expression and prognostic value of VISTA in HCC and classify tumor microenvironments (TMEs) based on VISTA and CD8+ tumor-infiltrating lymphocytes (TILs).

Antipsychotic-Free Status in Community-Dwelling Patients With Schizophrenia in China: Comparisons Within and Between Rural and Urban Areas.

Objective: To date, no study has specifically compared antipsychotic-free patients with schizophrenia living in the community between rural and urban areas. This study examined the rural-urban differences among antipsychotic-free community-dwelling individuals with schizophrenia in China.

Methods: Data on 1,365 community-dwelling patients with schizophrenia (n = 742 in a rural area and n = 623 in an urban area) with diagnoses according to DSM-IV or ICD-10 were collected by interviews during 2013-2014 and 2015-2016.

Afatinib as First-line Treatment of Older Patients With EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Subgroup Analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 Trials.

Background: Afatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm) non-small-cell lung cancer (NSCLC).

Patients And Methods: Treatment-naive patients with advanced EGFRm NSCLC were randomized to afatinib (40 mg/d) versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine (LUX-Lung 6 [LL6]), or versus gefitinib (250 mg/d; LUX-Lung 7 [LL7]). We report subgroup analyses according to age, including 65 years or older versus younger than 65 years (preplanned; LL3/LL6) and additional cutoffs up to 75 years and older (exploratory; LL7).

Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non-Small-Cell Lung Cancer.

Purpose Approximately 1% to 2% of non-small-cell lung cancers (NSCLCs) harbor a c-ros oncogene 1 ( ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study. We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC.

The Modifying Effect of a Functional Variant at the miRNA Binding Site in E2F1 Gene on Recurrence of Oropharyngeal Cancer Patients with Definitive Radiotherapy.

Human papillomavirus (HPV) activates E2F1-driven transcription via the E7-RB-E2F1 pathway. A polymorphism in the 3' UTR of E2F1 gene may disrupt a binding site for miRNA and may affect its transcription level, thus modifying the susceptibility to radiotherapy and outcomes through this pathway. We evaluated the association of a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) with risk of recurrence of SCCOP in a cohort of 1008 patients.

Clinical predictor of postoperative hyperkalemia after parathyroidectomy in patients with hemodialysis.

Objective: Hyperkalaemia is one of the most common reasons for patients requiring emergency treatment. This study is to investigate the risk factors of postoperative hyperkalemia in renal failure patients undergoing parathyroidectomy with autotransplantation (PTXa).

Methods: One hundred and eight patients [ 54 men and 54 women; age, 45.

Mobile Phone Dependence, Social Support and Impulsivity in Chinese University Students.

This study examined the frequency of mobile phone dependence in Chinese university students and explored its association with social support and impulsivity. Altogether, 909 university students were consecutively recruited from a large university in China. Mobile phone use, mobile phone dependence, impulsivity, and social support were measured with standardized instruments.

A novel generation 1928zT2 CAR T cells induce remission in extramedullary relapse of acute lymphoblastic leukemia.

Background: Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promise in the treatment of B cell acute lymphocytic leukemia (B-ALL). However, its efficacy in B-ALL patients with extramedullary involvement is limited due to poor responses and neurotoxicity. Here, we utilized a third generation of CAR T cell vector, which contains the Toll/interleukin-1 receptor (ITR) domain of Toll-like receptor 2 (TLR2), to generate 1928zT2 T cells targeting CD19, and evaluated the efficacy of 1928zT2 T cells in relapse or refractory B-ALL patients with extramedullary involvement.

Acoustic and Perceptual Analyses of Adductor Spasmodic Dysphonia in Mandarin-speaking Chinese.

Objective: The objective of this study was to examine the perceptual structure and acoustic characteristics of speech of patients with adductor spasmodic dysphonia (ADSD) in Mandarin.

Study Design: Case-Control Study MATERIALS AND METHODS: For the estimation of dysphonia level, perceptual and acoustic analysis were used for patients with ADSD (N = 20) and the control group (N = 20) that are Mandarin-Chinese speakers. For both subgroups, a sustained vowel and connected speech samples were obtained.

Rutaecarpine Suppresses Proliferation and Promotes Apoptosis of Human Pulmonary Artery Smooth Muscle Cells in Hypoxia Possibly Through HIF-1α-Dependent Pathways.

Purpose: The aim of this study is to investigate the potential roles of Rutaecarpine (Rut) in hypoxia-induced human pulmonary artery smooth muscle cells (HPASMCs) model.

Methods: HPASMCs were cultured with or without hypoxia followed by Rut administration. Cytotoxicity and cell proliferation were assessed by CCK-8 and Cell counting method.

Vascular dysfunction of postural tachycardia syndrome in children.

Background: Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic intolerance, and its incidence in children is approximately 6.8% [1]. The pathogenesis of POTS is complex with multiple, overlapping, interacting pathophysiological mechanisms.

PFKFB3 is involved in breast cancer proliferation, migration, invasion and angiogenesis.

6-Phosphofructo 2-kinase/fructose 2, 6-bisphosphatase 3 (PFKFB3) has been reported to be overexpressed in human cancer tissues and to promote the proliferation and migration of cancer cells. However, the role of PFKFB3 in the progression and prognosis of breast cancer is not yet fully understood. In the present study, we investigated the specific role of PFKFB3 in breast cancer progression and its preliminary mechanisms of action.

Toll-like receptor-9 is involved in the development of B cell stimulating factor-induced systemic lupus erythematosus.

The objective of the present study was to investigate the role of Toll-like receptor (TLR)-9 in B lymphocyte stimulating factor (BLyS)-induced systemic lupus erythematosus (SLE) in mice. The anti-double stranded (ds)DNA antibody titer, levels of complement proteins (C3 and C4), interleukin (IL)-10 and the disease activity [assessed by the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level] were measured. A total of 21 transgenic female mice (aged 8-10 weeks and weighing 30-40 g) expressing the Epstein-Barr virus membrane antigen, BLLF1, were studied.

Hypercapnia induces IL-1β overproduction via activation of NLRP3 inflammasome: implication in cognitive impairment in hypoxemic adult rats.

Background: Cognitive impairment is one of common complications of acute respiratory distress syndrome (ARDS). Increasing evidence suggests that interleukin-1 beta (IL-1β) plays a role in inducing neuronal apoptosis in cognitive dysfunction. The lung protective ventilatory strategies, which serve to reduce pulmonary morbidity for ARDS patients, almost always lead to hypercapnia.

Survival in Vivo Canine Phonation Model Without Stimulation.

Objectives: We describe a survival nonstimulated in vivo canine phonation model using distending laryngoscope, cramp frame, and constant humidified glottal airflow to elicit phonation.

Methods: Five beagle dogs were involved in this study. One cuffed endotracheal tube was placed below the glottis through the tracheotomy and delivered humidified airflow to the glottis.

[Effect of different time windows and interventions on skin pressure ulcers and ischemia-reperfusion injury in rats].

Objective: To observe the effect of different time windows and interventions on skin pressure ulcers and ischemia-reperfusion (I/R) injury in rats.

Methods: Sixty?eight SD rats were randomly divided into blank control group (n=4) and model group (n=64). The rats in the model group were randomly divided into group A (n=32) without intervention and group B (n=32) with post?conditioning.

Stromal PD-L1-Positive Regulatory T cells and PD-1-Positive CD8-Positive T cells Define the Response of Different Subsets of Non-Small Cell Lung Cancer to PD-1/PD-L1 Blockade Immunotherapy.

Introduction: Inhibition of programmed cell death-1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) by using an immune checkpoint inhibitor has emerged as a promising immunotherapy for NSCLC. The correlation of PD-L1 expression in tumor cells with treatment outcomes has been reported in many pivotal trials; however, the relationship remains unclear. Here, we demonstrate that those patients with both high density of PD-1-positive CD8 and PD-L1-positive CD4-positive CD25-positive (PD-1 PD-L1) regulatory T cells (Tregs) have a better response to PD1/PD-L1 blockade.