Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma

Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that reduction of lysyl oxidase (Lox) in Lkb1-deficient lung ADC decreases collagen disposition and triggers extracellular matrix remodelling and upregulates p63 expression, a SCC lineage survival oncogene. Pharmacological Lox inhibition promotes the transdifferentiation, whereas ectopic Lox expression significantly inhibits this process. Notably, ADC and SCC show differential responses to Lox inhibition. Collectively, our findings demonstrate the de novo transdifferentiation of lung ADC to SCC in mice and provide mechanistic insight that may have important implications for lung cancer treatment

The Association of Hypertension with Obesity and Metabolic Abnormalities among Chinese Children

A total of 8898 Chinese children (4580 boys and 4318 girls) aged 7–13 years in 6 cities of east China were recruited. Data on height, weight, waist circumference, blood pressure, serum lipid profiles, glucose, and insulin were collected. The overall prevalence of hypertension was 11.1%. Overweight and obese children had a higher risk of developing hypertension than their counterparts (29.1%, 17.4%, and 7.8%, resp.) (P=0.0001). The means levels of triglycerides, glucose, insulin, and HOMA-IR (1.0 mmol/L, 4.5 mmol/L, 8.4 mU/mL and 1.7, resp.) among hypertensive children were all significantly higher than their normotensive counterparts (0.8 mmol/L, 4.5 mmol/L, 5.9 mU/mL, and 1.2, resp.) (P=0.0001). Compared with the healthy children, the risk (odds ratio, OR) of having hypertension among children with high triglycerides, hyperglycemia, and metabolic syndrome was 1.4 (95% confidence interval (CI): 1.0–2.0, P=0.0334), 1.5 (95% CI: 0.9–2.5, P=0.0890), and 2.8 (95%CI: 1.5–5.4, P=0.0014), respectively, after controlling for age, gender, BMI, income level, parents' education level and puberty. In conclusion, overweight and obese children have higher risk of having hypertension and children with dyslipidemia, hyperglycemia, and metabolic syndrome and higher HOMA-IR have higher risk of developing hypertension

Spectrum of Oncogenic Driver Mutations in Lung Adenocarcinomas from East Asian Never Smokers

PURPOSE:We previously showed that 90% (47 of 52; 95% CI, 0.79 to 0.96) of lung adenocarcinomas from East Asian never-smokers harbored well-known oncogenic mutations in just four genes: EGFR, HER2, ALK, and KRAS. Here, we sought to extend these findings to more samples and identify driver alterations in tumors negative for these mutations. EXPERIMENTAL DESIGN:We have collected and analyzed 202 resected lung adenocarcinomas from never smokers seen at Fudan University Shanghai Cancer Center. Since mutations were mutually exclusive in the first 52 examined, we determined the status of EGFR, KRAS, HER2, ALK, and BRAF in stepwise fashion as previously described. Samples negative for mutations in these 5 genes were subsequently examined for known ROS1 fusions by RT-PCR and direct sequencing. RESULTS:152 tumors (75.3%) harbored EGFR mutations, 12 (6%) had HER2 mutations, 10 (5%) had ALK fusions all involving EML4 as the 5' partner, 4 (2%) had KRAS mutations, and 2 (1%) harbored ROS1 fusions. No BRAF mutation were detected. CONCLUSION:The vast majority (176 of 202; 87.1%, 95% CI: 0.82 to 0.91) of lung adenocarcinomas from never smokers harbor mutant kinases sensitive to available TKIs. Interestingly, patients with EGFR mutant patients tend to be older than those without EGFR mutations (58.3 Vs 54.3, P = 0.016) and patient without any known oncogenic driver tend to be diagnosed at a younger age (52.3 Vs 57.9, P = 0.013). Collectively, these data indicate that the majority of never smokers with lung adenocarcinoma could benefit from treatment with a specific tyrosine kinase inhibitor

The nutrition-based comprehensive intervention study on childhood obesity in China (NISCOC): a randomised cluster controlled trial

<p>Abstract</p> <p>Background</p> <p>Childhood obesity and its related metabolic and psychological abnormalities are becoming serious health problems in China. Effective, feasible and practical interventions should be developed in order to prevent the childhood obesity and its related early onset of clinical cardiovascular diseases. The objective of this paper is to describe the design of a multi-centred random controlled school-based clinical intervention for childhood obesity in China. The secondary objective is to compare the cost-effectiveness of the comprehensive intervention strategy with two other interventions, one only focuses on nutrition education, the other only focuses on physical activity.</p> <p>Methods/Design</p> <p>The study is designed as a multi-centred randomised controlled trial, which included 6 centres located in Beijing, Shanghai, Chongqing, Shandong province, Heilongjiang province and Guangdong province. Both nutrition education (special developed carton style nutrition education handbook) and physical activity intervention (Happy 10 program) will be applied in all intervention schools of 5 cities except Beijing. In Beijing, nutrition education intervention will be applied in 3 schools and physical activity intervention among another 3 schools. A total of 9750 primary students (grade 1 to grade 5, aged 7-13 years) will participate in baseline and intervention measurements, including weight, height, waist circumference, body composition (bioelectrical impendence device), physical fitness, 3 days dietary record, physical activity questionnaire, blood pressure, plasma glucose and plasma lipid profiles. Data concerning investments will be collected in our study, including costs in staff training, intervention materials, teachers and school input and supervising related expenditure.</p> <p>Discussion</p> <p>Present study is the first and biggest multi-center comprehensive childhood obesity intervention study in China. Should the study produce comprehensive results, the intervention strategies would justify a national school-based program to prevent childhood obesity in China.</p> <p>Trial Registration</p> <p>Chinese clinical trial registry (Primary registry in the WHO registry network) Identifier: ChiCTR-TRC-00000402</p

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

Prevalence of the metabolic syndrome among children from six cities of China

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) in childhood can increase the risk of cardiovascular disease, diabetes mellitus and dyslipidemia in adulthood, which is of increasing concern in transitional and advanced economies. The aim of the current study was to explore the prevalence of MetS among children from six cities of China.</p> <p>Methods</p> <p>A total of 8,764 children (4,495 boys, 4,269 girls) aged 7-11 years were randomly selected from 6 cities of China. MetS was mainly defined by the criteria proposed by International Diabetes Federation (IDF).</p> <p>Results</p> <p>The overall prevalence of MetS for children older than 10 years was 0.8% by IDF definition. Obese children had significantly higher MetS prevalence compared with their counterparts with overweight (6.6% vs. 0.9%, <it>p </it>< 0.01) and normal weight (6.6% vs. 0.05%, <it>p </it>< 0.01). The prevalence of abdominal obesity, high triglycerides, low high density lipoprotein cholesterol, hypertension and high glucose among obese children was 93.4%, 16.5%, 14.3%, 7.3% and 4.0%, respectively, which significantly higher than those among overweight children (37.0%, 6.1%, 10.0%, 4.2%, and 3.3%, respectively) and among normal weight children (1.2%, 3.3%, 4.0%, 1.7% and 2.5%, respectively). The proportion of children with at least one, two, and three items of the metabolic abnormalities were 25.0%, 5.4% and 0.9%, respectively. Metabolic abnormalities were also present in children under 10 years of age.</p> <p>Conclusions</p> <p>The early onset of MetS among children and relatively high proportions of children with at least one or two metabolic abnormalities in cities of China can increase the risk of developing MetS. It implies the necessity to take effective actions to control and prevent the rapid development of obesity among children in developing countries, especial those undergoing transition to a Western lifestyle.</p

Object Detection with the Addition of New Classes Based on the Method of RNOL

Object detection plays an important role in many computer vision applications. Innovative object detection methods based on deep learning such as Faster R-CNN, YOLO, and SSD have achieved state-of the-art results in terms of detection accuracy. There have been few studies to date on object detection with the addition of new classes, however, though this problem is often encountered in the industry. Therefore, this issue has important research significance and practical value. On the premise that the old class samples are available, a method of reserving nodes in advance in the output layer (RNOL) was established in this study. Experiments show that RNOL can achieve high detection accuracy in both new and old classes over a short training time while outperforming the traditional fine-tuning method