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Overdiagnosis of lung cancer by low-dose CT (LDCT) screening has raised concerns globally. LDCT screening has been used widely in employee health examinations in China since 2011.Has the increasing use of LDCT in low-risk populations in China led to lung cancer overdiagnosis?A total of 34,152 incident cases of and 27,208 deaths resulting from lung cancer in a population of approximately 3 million were derived from the Cancer Surveillance of Shanghai between 2002 and 2017. Changes in stage-specific and histologic type-specific incidence and mortality and incidence rate ratio (IRR) relative to the base year 2002 or to the period 2002 through 2005 were calculated by sex and were used to evaluate potential overdiagnosisve of lung cancer.In men, both age-adjusted incidence of and mortality as a result of lung cancer decreased significantly up to 2008 and thereafter remained stable; in women, the incidence increased rapidly from 2011 (annual percentage change, 11.98%; 95% CI, 9.57%-14.45%), whereas the mortality declined persistently. The upward trend of incidence mainly was observed in lung adenocarcinoma in both sexes, with a sharper increase from 2012 through 2017. In men, the incidence of early-stage cancer increased 6.9 per 100,000 (95% CI, 5.1-8.7 per 100,000) and was accompanied by 5.5 per 100,000 (95% CI, -9.2 to -1.7 per 100,000) decline in late-stage cancer from 2002 through 2017. In women, early-stage incidence rose 16.1 per 100,000 (95% CI, 14.0-18.3 per 100,000), but no significant decline in late-stage cancer was found (absolute difference, -0.6 per 100,000; 95% CI, -2.8 to 1.7 per 100,000). The IRR was highest in most recent period and increased most in young women, mainly for early-stage cancer or lung adenocarcinoma.The results provide evidence at a population level for lung cancer overdiagnosis in Chinese women resulting from increasing LDCT screening in the low-risk populations. Criteria for LDCT screening and management of screening-detected nodules need to be addressed fully for expanded application of LDCT screening in China.

The survival benefit of adjuvant radiotherapy in T4 colon cancer (CC) remains controversial, with conflicting results reported in the literature. This study aimed to explore the relationship between pretreatment carcinoembryonic antigen (CEA) level and overall survival (OS) of pT4N+ CC patients treated with adjuvant radiotherapy. Data of pT4N+ CC patients who received curative surgery between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome was OS, and subgroup analysis was conducted according to pretreatment CEA level. A total of 8763 patients were eligible for our study. In the CEA-normal group, 151 patients received adjuvant radiotherapy, while 3932 patients did not. In the CEA-elevated group, 212 patients received adjuvant radiotherapy, while 4468 patients did not. In general, adjuvant radiotherapy was associated with better OS in pT4N+ CC patients (HR = 0.846, 95% CI = 0.733–0.976, P = 0.022 ). Intriguingly, only patients with an elevated pretreatment CEA level gained a survival benefit from adjuvant radiotherapy (HR = 0.782; 95% CI = 0.651–0.939; P = 0.008 ) while those with a normal pretreatment CEA level did not (HR = 0.907; 95% CI = 0.721–1.141; P = 0.403 ). Multivariable Cox regression analysis demonstrated that adjuvant radiotherapy was an independent protective factor in pT4N+ CC patients with an elevated pretreatment CEA level. Pretreatment CEA levels could serve as a potential biomarker to screen pT4N+ CC patients who would benefit from adjuvant radiotherapy.

Lung cancer has the highest mortality among cancers, represented by a low 5-year survival rate. The function of the immune system has a profound influence on the development and progression of lung cancer. Thus genetic variants of the immune-related genes may serve as potential predictors of non-small cell lung cancer (NSCLC) survival.In the present study, we conducted a two-stage survival analysis in 1,531 NSCLC patients and assessed the associations between genetic variants in the immune-activation gene set and the overall survival (OS) of NSCLC patients. The validated variants were further subjected to functional annotation and in vitro experiments.We identified 25 SNPs spanning six loci associated with NSCLC OS after multiple-testing corrections in all datasets, in which two variants, PSMA4 rs12901682 A C and VAV2 rs12002767 C T, were shown to potentially affect lung cancer OS by cis-regulating the expression of the corresponding genes [(HR (95% CI) = 0.76 (0.65-0.89) and 1.36 (1.12-1.65), p = 4.29 × 10Our findings provide new insights into the role of genetic variants in the immune-activation pathway genes in lung cancer progression.

Genome‐wide association studies (GWAS) have identified some single nucleotide polymorphisms (SNPs) associated with the risk of gastric cancer (GCa). However, currently, there is no published predictive model to assess the risk of GCa. In the present study, risk‐associated SNPs derived from GWAS and large meta‐analyses were selected to construct a predictive model to assess the risk of GCa. A total of 1115 GCa cases and 1172 controls from the eastern Chinese population were included. Logistic regression models were used to identify SNPs that correlated with the risk of GCa. A predictive model to assess the risk of GCa was established by receiver operating characteristic curve analysis. Multifactor dimensionality reduction (MDR) and classification and regression tree (CART) were applied to calculate the effect of high‐order gene‐environment interactions on risk of the cancer. A total of 42 SNPs were selected for further analysis. The results revealed that ASH1L rs80142782, PKLR rs3762272, PRKAA1 rs13361707, MUC1 rs4072037, PSCA rs2294008, and PLCE1 rs2274223 polymorphisms were associated with a risk of GCa. The area under curve considering both genetic factors and BMI was 3.10% higher than that of BMI alone. MDR analysis revealed that rs13361707 and rs4072307 variants and BMI had interaction effects on susceptibility to GCa, with the highest predictive accuracy (61.23%) and cross‐validation consistency (100/100). CART analysis also supported this interaction model that non‐overweight status and a six SNP panel could synergistically increase the susceptibility to GCa. The six SNP panel for predicting the risk of GCa may provide new tools for prevention of the cancer based on GWAS and large meta‐analyses derived genetic variants., We identifed a six‐SNPs panel from GWAS and large meta‐analysis for predicting risk of gastric cancer, which may provide new tools for gastric cancer prevention.

Human leukocyte antigen (HLA) is highly polymorphic, driving antigen presentation, complement cascade and leukocyte maturation against cancer cells. Therefore, we extracted genotyping data in the HLA region from an ongoing Chinese genome-wide association study of non-small cell lung cancer (NSCLC). Using deep sequencing data of 10 689 healthy Han Chinese, we imputed for untyped genetic variants in the HLA region, followed by a two-stage survival analysis of 1531 NSCLC patients. In the discovery stage of 758 patients, we identified 301 out of 15 138 single-nucleotide polymorphisms to be independently associated with overall survival [P < 0.05 and Bayesian false-discovery probability < 0.8]. In further validation of another 773 patients, we confirmed chromosome 6p21, rs241424 (located at intron 3 of TAP2) and rs6457642 as two independent survival predictors. In the combined analysis of 1531 NSCLC patients, rs241424 G>A and rs6457642 C>T were associated with a hazards ratio of 1.26 [95% confidence interval (CI) = 1.14–1.40 and P = 4.04 × 10−6] and 0.76 (95% CI = 0.66–0.87 and P = 1.16 × 10−4), respectively. The analysis of publically available ChIP-sequencing and Hi-C data found that the rs241424 locus was involved in potential cis-regulatory element by a long-range interaction with the HLA-DQA1 promoter. Additional expression quantitative trait loci analysis showed that the rs241424 G>A change decreased HLA-DQA1 mRNA expression. Furthermore, expression levels of HLA-DQA1 were lower in lung cancer tissues than in adjacent normal tissues, and the lower expression was associated with a worse prognosis for patients with lung adenocarcinoma. Collectively, HLA genetic variants may modulate OS of NSCLC patients, possibly via a mechanism of long-range promoter interaction regulating HLA-DQA1 expression.

The Notch signaling pathway is involved in the progression of esophageal squamous cell carcinoma (ESCC), although the roles of single nucleotide polymorphisms (SNPs) of the Notch signaling pathway genes in the process remain unknown.The present study included 1009 patients with histopathologically diagnosed ESCC at Fudan University Shanghai Cancer Center. Two-stage multivariate Cox proportional hazards regression analysis was used to estimate associations between 13,248 SNPs in 103 Notch signaling pathway genes and overall survival of the patients.We found that overall survival of the patients was significantly associated with genotypes of HDAC9 rs1729318 (AT+TT vs. AA: hazard ratio = 1.44, 95% confidence interval = 1.16-1.80, pThe results suggest that these two potential functional SNPs on HDAC9 may serve as biomarkers for predicting survival of ESCC patients. However, further studies are needed to confirm these findings.

Background Genetic variation has an important role in the development of non-small-cell lung cancer (NSCLC). However, genetic factors for lung cancer have not been fully identified, especially in Chinese populations, which limits the use of existing polygenic risk scores (PRS) to identify subpopulations at high risk of lung cancer for prevention. We therefore aimed to identify novel loci associated with NSCLC risk, and generate a PRS and evaluate its utility and effectiveness in the prediction of lung cancer risk in Chinese populations. Methods To systematically identify genetic variants for NSCLC risk, we newly genotyped 19 546 samples from Chinese NSCLC cases and controls from the Nanjing Medical University Global Screening Array Project and did a meta-analysis of genome-wide association studies (GWASs) of 27 120 individuals with NSCLC and 27 355 without NSCLC (13 327 cases and 13 328 controls of Chinese descent as well as 13 793 cases and 14 027 controls of European descent). We then built a PRS for Chinese populations from all reported single-nucleotide polymorphisms that have been reported to be associated with lung cancer risk at genome-wide significance level. We evaluated the utility and effectiveness of the generated PRS in predicting subpopulations at high-risk of lung cancer in an independent prospective cohort of 95 408 individuals from the China Kadoorie Biobank (CKB) with more than 10 years' follow-up. Findings We identified 19 susceptibility loci to be significantly associated with NSCLC risk at p≤5·0 × 10−8, including six novel loci. When applied to the CKB cohort, the PRS of the risk loci successfully predicted lung cancer incident cases in a dose-response manner in participants at a high genetic risk (top 10%) than those at a low genetic risk (bottom 10%; adjusted hazard ratio 1·96, 95% CI 1·53–2·51; ptrend=2·02 × 10−9). Specially, we observed consistently separated curves of lung cancer events in individuals at low, intermediate, and high genetic risk, respectively, and PRS was an independent effective risk stratification indicator beyond age and smoking pack-years. Interpretation We have shown for the first time that GWAS-derived PRS can be effectively used in discriminating subpopulations at high risk of lung cancer, who might benefit from a practically feasible PRS-based lung cancer screening programme for precision prevention in Chinese populations. Funding National Natural Science Foundation of China, the Priority Academic Program for the Development of Jiangsu Higher Education Institutions, National Key R and D Program of China, Science Foundation for Distinguished Young Scholars of Jiangsu, and China's Thousand Talents Program.

The prognostic value of tumor regression grade (TRG) in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy has been explored extensively. However, whether TRG is predictive of outcome in colon cancer following preoperative chemotherapy has not been reported.A total of 276 colon cancer patients who had undergone preoperative chemotherapy and surgery in Fudan University Shanghai Cancer Center during the period March 2014 through November 2019 were recruited in this study. 113 (40.9%) and 163 (59.1%) patients were diagnosed with locally advanced colon cancer (LACC) and metastatic colon cancer (mCC) before preoperative chemotherapy, respectively. The TRG was divided into TRG0 (complete response), TRG1 (good response), TRG2 (moderate response), and TRG3 (poor response).Of the 276 patients 4.0% were TRG0, 5.4% were TRG1, 29.3% were TRG2, 61.2% were TRG3. TRG0 and TRG1 or TRG0, TRG1 and TRG2 were combined to simplify analysis due to limited sample size. In entire cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 80.0%, 68.8% and 43.3% (P = .003). In LACC cohort, TRG was not associated with patients' prognosis, which largely resulted from limited outcome events. In mCC cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 74.3%, 62.8% to 28.1% (P0.001). Multivariate analysis demonstrated that TRG was an independent prognostic factor for overall survival in both entire cohort and mCC cohort (TRG3 vs. TRG0-2).TRG is a prognostic factor in predicting long-term outcomes of mCC patients treated with preoperative chemotherapy.

Phase-change material such as Ge 2 Sb 2 Te 5 is usually utilized to store data due to the pronounced contrast in optical and electrical properties between crystalline and amorphous phases. As the density differs in the two phases, it is necessary to explore the influence of pressure on the structures of Ge 2 Sb 2 Te 5 , especially for the supercooled liquid which is an inevitable state in the formation of the two phases. The short-range structures in supercooled liquid Ge 2 Sb 2 Te 5 under compression have been investigated by using ab initio molecular dynamics simulation. The supercooled liquid eventually changes to a solid with an increase in pressure. During the process, tetrahedrons decrease slightly, revealing that tetrahedral structures are insensitive to the pressure. Octahedrons increase as the pressure is less than 3.7 GPa and then decrease, suggesting that a moderate pressure can promote the formation of octahedrons. The body-centered-cubic, face-centered-cubic and hexagonal closed-packed structures are observed at 9.9 GPa and then increase gradually. Additionally, it is noticed that Sb- and Te-centered clusters prefer Ge-centered clusters to forming the high-coordinated short-range structures during the compression process. Our research make us aware of the effects of pressure on short-range structures in supercooled liquid, which is of great importance in the application of phase-change materials.

BACKGROUND: Although microsatellite instability (MSI) is a powerful predictive biomarker for the efficacy of immunotherapy, the mechanism of MSI in sporadic gastrointestinal cancer is not fully understood. However, epigenetics, particularly microRNAs, has been suggested as one of the main regulators that contribute to the MSI formation. METHODS: We used microRNA expression data of 386 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database to identify differential microRNA expression profiles by different MSI status. We also obtained putative common target genes of the top differential microRNAs with miRanda online tools, and we analyzed these data by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment (KEGG). RESULTS: We found that 56 and 67 gastric adenocarcinoma samples were positive for low and high MSI, respectively, and that a high MSI status was associated with age, sex and subregion (P=0.049, 0.014 and 0.007, respectively). In the 67 samples with a high MSI status, expression levels of 14 microRNAs were upregulated but five microRNAs were downregulated as assessed by the fold change (FC), compared with that of the 56 samples with a low MSI status (P2). Further analysis suggested that the expression of miR-210-3p, miR-582-3p, miR-30a-3p and miR-105-5p predicted a high MSI status (P=4.93×10(−10), 5.63×10(−10), 3.23×10(−9) and 7.64×10(−4), respectively). Regulation of the transcription pathways ranked the top of lists from both GO and KEGG analyses, and these microRNAs might regulate DNA damage-repair genes that were also associated with a high MSI status. CONCLUSIONS: MiR-30a-3p and miR-105-5p are potential biomarkers for the MSI-H gastric adenocarcinoma, possibly by altering expression of DNA damage-repair genes.

We previously reported that some single nucleotide polymorphisms (SNPs) of candidate genes involved in the MTOR complex1 (MTORC1) were associated with risk of gastric cancer (GCa). In the present study, we further evaluated associations of eight potentially functional SNPs of MTOR, MLST8 and RPTOR with survival of 1002 GCa patients and also investigated molecular mechanisms underlying such associations. Specifically, we found that the MTOR rs2536 C allele at the microRNA binding site was independently associated with a 26% reduction of death risk (HR = 0.74, 95% CI = 0.57-0.96, p = 0.022). The results remained noteworthy with a prior false positive probability of 0.1. Genotype-phenotype correlation analysis in 144 patients' adjacent normal gastric tissue samples revealed that the MTOR expression levels were lower in rs2536 TC/CC carriers than that in wild-type TT carriers (p = 0.043). Dual luciferase assays revealed that the rs2536 C allele had a higher binding affinity to microRNA-150, leading to a decreased transcriptional activity of MTOR, compared to the rs2536 T allele. Further functional analysis revealed that MTOR knockdown by small interference RNA impaired proliferation, migration, and invasion ability in GCa cell lines. In conclusion, The MTOR rs2536 T > C change may be a biomarker for survival of Chinese GCa patients, likely by modulating microRNA-induced gene expression silencing. Additional studies are needed to validate our findings.

To identify genetic variants in Notch signalling pathway genes that may predict survival of Han Chinese patients with epithelial ovarian cancer (EOC), we analysed a total of 1273 single nucleotide polymorphisms (SNPs) within 75 Notch genes in 480 patients from a published EOC genomewide association study (GWAS). We found that PSEN1 rs165934 and MAML2 rs76032516 were associated with overall survival (OS) of patients by multivariate Cox proportional hazards regression analysis. Specifically, the PSEN1 rs165934 AA genotype was associated with a poorer survival (adjusted hazards ratio [adjHR] = 1.41, 95% CI = 1.07‐1.84, and P = .014), compared with the CC + CA genotype, while MAML2 rs76032516 AA + AC genotypes were associated with a poorer survival (adjHR = 1.58, 95% CI = 1.16‐2.14, P = .004), compared with the CC genotype. The combined analysis of these two SNPs revealed that the death risk increased as the number of unfavourable genotypes increased in a dose‐dependent manner (P trend < .001). Additionally, the expression quantitative trait loci analysis revealed that the SNP rs165932 in the rs165934 LD block (r 2 = .946) was associated with expression levels of PSEN1, which might be responsible for the observed association with SNP rs165934. The associations of PSEN1 rs165934 and MAML2 rs76032516 of the Notch signalling pathway genes with OS in Chinese EOC patients are novel findings, which need to be validated in other large and independent studies.

Gene-environmental interaction could be the major cause of autism. The aim of the current study is to detect the effects of valproic acid on gene expression profiles and alternatively spliced genes in the prefrontal cortex in rat models of autism. Female rats received a single intraperitoneal injection of 600 mg/kg valproic acid at day 12.5 post-conception, and controls were injected with saline. Only male offspring were employed in the current study. RNA sequencing was used to investigate transcriptome in the prefrontal cortex of VPA-exposed rats. There were 3228 differently expressed genes and 637 alternative spliced genes, in VPA rats compared to controls. Pathways enrichment among the differently expressed genes and alternatively spliced genes were associated with neurological diseases and neural system development. The results implied VPA affected transcriptional and splicing events genome-wide and the transcriptional and splicing events may be associated with the autistic behaviors of VPA rats.

Platinum-based chemotherapy (PBC) in combination with the 3rd generation drugs is the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC); however, the efficacy is severely hampered by grade 3-4 toxicities. Nucleotide excision repair (NER) pathway is the main mechanism of removing platinum-induced DNA adducts that contribute to the toxicity and outcome of PBC. We analyzed data from 710 Chinese NSCLC patients treated with PBC and assessed the associations of 25 potentially functional single nucleotide polymorphisms (SNPs) in nine NER core genes with overall, gastrointestinal and hematologic toxicities. Through a two-phase study, we found that ERCC4 rs1799798 was significantly associated with overall and gastrointestinal toxicities [all patients: GA/AA vs. GG, odds ratio (OR)adj =1.61 and 2.35, 95% confidence interval (CI)=1.11-2.33 and 1.25-4.41, and Padj =0.012 and 0.008, respectively]. Our prediction model for the overall toxicity incorporating rs1799798 demonstrated a significant increase in the area under the curve (AUC) value, compared to that for clinical factors only (all patients: AUC = 0.61 vs. 0.59, 95% CI = 0.57-0.65 vs. 0.55-0.63, P = 0.010). Furthermore, the ERCC4 rs1799798 A allele was associated with lower ERCC4 mRNA expression levels according to the expression quantitative trait loci (eQTL) analysis. Our study provided some new clue in future development of biomarkers for assessing toxicity and outcomes of platinum drugs in lung cancer treatment.

Elevated blood pressure (BP) is a major global risk factor for cardiovascular disease. Genome-wide association studies have identified several genetic variants at the NPR3 locus associated with BP, but the functional impact of these variants remains to be determined. Here we confirmed, by a genome-wide association study within UK Biobank, the existence of two independent BP-related signals within NPR3 locus. Using human primary vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) from different individuals, we found that the BP-elevating alleles within one linkage disequilibrium block identified by the sentinel variant rs1173771 was associated with lower endogenous NPR3 mRNA and protein levels in VSMCs, together with reduced levels in open chromatin and nuclear protein binding. The BP-elevating alleles also increased VSMC proliferation, angiotensin II-induced calcium flux and cell contraction. However, an analogous genotype-dependent association was not observed in vascular ECs. Our study identifies novel, putative mechanisms for BP-associated variants at the NPR3 locus to elevate BP, further strengthening the case for targeting NPR-C as a therapeutic approach for hypertension and cardiovascular disease prevention.

Structures and relative stabilities of small Co n clusters (n = 1–12) on a Cu(111) surface are studied using molecular dynamics simulations. It is shown that the supported clusters are all in two-dimensional island structures of the edges forming square microfacets (A step) and/or triangular microfacets (B step) with the substrate. For non-magic-number clusters, the lowest energy structures are the ones of the edges with more A steps and the most unstable structures are the ones of the edges with only A steps or B steps due to the lattice mismatch of the Co n /Cu(111) system. Magic number clusters are truncated triangular or elongated shapes with a closed atomic shell and maximum nearest-neighbor bonds. In addition, the anomalous mobility is found for Co 3 and Co 6 clusters in the diffusion processes of these clusters. The concerted translation and rotation movements are responsible for their special diffusion behaviors.

DNA repair protects genomic integrity and may modulate chemotherapy efficacy. Few large-scale studies have evaluated predictive roles of genetic variants of DNA repair genes in survival of Chinese gastric cancer (GCa) patients treated with chemotherapy. Here, we assessed the roles of 35 single nucleotide polymorphisms (SNPs) in DNA repair genes in survival of 1,002 GCa patients, of whom 694 received chemotherapy and 308 did not. Among patients receiving chemotherapy, the ERCC1 rs2298881A allele was associated with a better survival [hazards ratio (HR) =0.82, 95% confidence interval (CI) =0.69-0.98; P = 0.03)], whereas two XRCC4 SNPs were associated with a worse survival (HR = 1.26, 95% CI = 1.03-1.54 for the rs10040363G allele, P = 0.02; and HR = 1.30, 95% CI = 1.06-1.59 for the rs2075685T allele, P = 0.01). These three SNPs were unique survival predictors for patients treated with chemotherapy (P 0.05 for all), suggesting that they modulated chemotherapy efficacy. Patients who received chemotherapy and had haplotypes with at least one death-risk allele in XRCC4 had a poor survival, and the trend for an increase in the number of death-risk alleles adversely affecting the survival was also observed in an allelic dose-dependent manner (Ptrend = 0.001). Further functional analysis revealed that the death-risk alleles up-regulated the gene expression, leading to a worse survival as suggested by our meta-analysis pooling both mRNA microarray data from the GEO database and published data [ERCC1: HR = 1.31 (1.08-1.58); P = 0.006]. These functional genetic variants may independently or jointly affect survival in chemotherapy-treated GCa patients by modulating the gene expression in the tumors. This article is protected by copyright. All rights reserved

Nucleotide excision repair (NER) plays a vital role in platinum-induced DNA damage during chemotherapy. We hypothesize that regulatory single nucleotide polymorphisms (rSNPs) of the core NER genes modulate clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy (PBS). We investigated associations of 25 rSNPs in eight NER genes with progression free survival (PFS) and overall survival (OS) in 710 NSCLC patients. We found that ERCC1 rs3212924 AG/GG and XPC rs2229090 GC/CC genotypes were associated with patients’ PFS (HRadj = 1.21, 95% CI = 1.03–1.43, Padj = 0.021 for ERCC1 and HRadj = 0.80, 95% CI = 0.68–0.94, Padj = 0.007 for XPC), compared with the AA and GG genotypes, respectively. The association of XPC rs2229090 was more apparent in adenocarcinoma than in squamous cell carcinoma patients. Additionally, ERCC4 rs1799798 GA/AA genotypes were associated with poorer OS (HRadj = 1.32, 95% CI = 1.04–1.69, Padj = 0.026), compared with the GG genotype. The expression quantitative trait loci analysis revealed that ERCC1 rs3212924 and XPC rs2229090 might regulate transcription of their genes, which is consistent with their associations with survival. Larger studies are needed to validate our findings with further functional studies to elucidate the mechanisms underlying these observed associations.

Background Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk. Methods In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 × 10−4 p=5 × 10−5 p=5 × 10−6 p=5 × 10−7, and p=5 × 10−8) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low [quintile 1 of the polygenic risk score], intermediate [quintile 2–4 of the polygenic risk score], and high [quintile 5 of the polygenic risk score]). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor. Findings The polygenic risk score derived from 112 single-nucleotide polymorphisms (p Interpretation Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer. Funding National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation.

Background: The shortage of healthcare workers is becoming a serious global problem. The underlying reasons may be specific to the healthcare system in each country. Over the past decade, medicine has become an increasingly unpopular profession in China due to the heavy workload, long-term training, and inherent risks. The ongoing COVID-19 pandemic has placed the life-saving roles of healthcare professionals under the spotlight. This public health crisis may have a profound impact on career choices in the young generation of Chinese. Methods: We conducted a questionnaire-based online survey on high school students and their parents from 24 provinces (or municipalities) of China. We investigated the change of interest in medical study due to the outbreak of COVID-19 and the motivational factors. Pearson correlation analysis was used to assess the correlation of static or dynamic interest of medical career selection with the reported number of COVID-19 cases. Maslow’s Hierarchy of Needs was used to explore underlying motivations for selection of medical-related degrees. The logistic regression model was adopted to analyze the main factors associated with students’ choices. Findings: A total of 21,085 students and 21,009 parents were included in the study. We observed an increased preference for medical study since the outbreak of COVID-19 in both students (17·5% to 29·6%) and parents (37·1% to 47·3%). Contribution to society and interest in medicine was rated as the main motivations. Additionally, students who were female, in the resit of graduate year and outside of Hubei province were significantly associated with a keen interest in medical study. Interpretation: This first multi-center cross-sectional study explores the positive change and noble motivations of students’ preferences in medical study during the COVID-19 pandemic. A longitudinal study is required to determine the persistence of their choices. Funding Statement: The Local High Level University Construction Project of Shanghai, China. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was approved by the Institutional review board of the Fudan University School of Public Health. Informed consent was waived because the questions were answered anonymously.

// Lei Cheng 1,2,* , Li-Xin Qiu 1,2,3,* , Ming Jia 1,2,* , Fei Zhou 1,2 , Meng-Yun Wang 1,2 , Ruo-Xin Zhang 1,2 , Yajun Yang 4,5 , Xiaofeng Wang 4,5 , Jiucun Wang 4,5 , Li Jin 4,5 and Qing-Yi Wei 1,2,6 1 Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Xuhui, Shanghai, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Xuhui, Shanghai, China 3 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Xuhui, Shanghai, China 4 Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China 5 Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China 6 Duke Cancer Institute, Duke University Medical Center, and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA * These authors have contributed equally to this work Correspondence to: Qing-Yi Wei, email: // Keywords : gastric cancer, genome-wide association study, genetic risk score, prognosis Received : May 30, 2016 Accepted : October 14, 2016 Published : November 04, 2016 Abstract Literature suggests that genetic variants associated with increased susceptibility to gastric cancer (GCa) are mostly located in genes involved in carcinogenesis and possibly tumor progression. Therefore, we hypothesize that high genetic susceptibility is also associated with prognosis of the patients. To test this hypothesis, we selected a total of 42 common genetic variants that were reportedly associated with GCa risk with a high level of evidence obtained from either genome-wide association studies (GWASs) or meta-analyses and performed survival analysis of patients used in a case-control analysis. We first used 1115 GCa cases and 1172 cancer-free controls of ethnic Han Chinese to construct a weighted genetic risk score (GRS). Then, we included 633 GCa cases with available clinical information, fit GRS in a fractional polynomial Cox proportional hazards regression model to investigate whether there is a dose-dependent effect of GRS on risk of death in survival analysis. Dynamic predictive value of genetic risk for prognosis was also calculated. The results showed that the increase of GRS had no effect on risk of death in these GCa patients. Compared with GCa patients with the medium GRS, there was no significant difference in survival in patients with either a low ( P = 0.349) or a high ( P = 0.847) GRS. The results unchanged when data were stratified by tumor stage and Lauren’s classification. Time-dependent predictive value for prognosis in considering both clinical factors and GRS was comparable with that in considering clinical factors alone, for either all patients ( P = 0.986) or stage- and Laruen type-based subgroups ( P > 0.05 for all). In conclusion, higher polygenic susceptibility loci for GCa may not indicate worse prognosis of Chinese patients. Additional variants of relevant genes modulating GCa patients’ survival need to be further identified.

Genome-wide association studies have revealed a relationship between inter-individual variation in blood pressure and the single nucleotide polymorphism rs13107325 in the SLC39A8 gene. This gene encodes the ZIP8 protein which co-transports divalent metal cations, including heavy metal cadmium, the accumulation of which has been associated with increased blood pressure. The polymorphism results in two variants of ZIP8 with either an alanine (Ala) or a threonine (Thr) at residue 391. We investigated the functional impact of this variant on protein conformation, cadmium transport, activation of signalling pathways and cell viability in relation to blood pressure regulation. Following incubation with cadmium, higher intracellular cadmium was detected in cultured human embryonic kidney cells (HEK293) expressing heterologous ZIP8-Ala391, compared with HEK293 cells expressing heterologous ZIP8-Thr391. This Ala391-associated cadmium accumulation also increased the phosphorylation of the signal transduction molecule ERK2, activation of the transcription factor NFκB, and reduced cell viability. Similarly, vascular endothelial cells with the Ala/Ala genotype had higher intracellular cadmium concentration and lower cell viability than their Ala/Thr counterpart following cadmium exposure. These results indicate that the ZIP8 Ala391-to-Thr391 substitution has an effect on intracellular cadmium accumulation and cell toxicity, providing a potential mechanistic explanation for the association of this genetic variant with blood pressure.

Although physicians learn about new medical technologies from their peers, the magnitude and source of peer influence is unknown. We estimate the effect of peer adoption of three first-in-class medications (dabigatran, sitigliptin, and aliskiren) on physicians' own adoption of those medications. We included 11,958 physicians in Pennsylvania prescribing anticoagulant, antidiabetic, and antihypertensive medications. We constructed 4 types of peer networks based on shared Medicare and Medicaid patients, medical group affiliation, hospital affiliation, and medical school/residency training. Instrumental variables analysis was used to estimate the causal effect of peer adoption (fraction of peers in each network adopting the new drug) on physician adoption (prescribing at least the median number prescriptions within 15 months of the new drug's introduction). We illustrate how physician network position can inform targeting of interventions to physicians by computing a social multiplier. Dabigatran was adopted by 25.2%, sitagliptin by 24.5% and aliskiren by 8.3% of physicians. A 10-percentage point increase in peer adoption in the patient-sharing network led to a 5.90% (SE = 1.50%, p

Phase-change memory is one of the most promising candidates for future memory technologies. However, most of the phase-change memories are based on chalcogenides, while other families of materials for this purpose remain insufficiently studied. In this work, we investigate the optical properties and microstructure of Ga16Sb84 by an in-situ ellipsometer and X-ray diffraction. Our experimental results reveal that the Ga16Sb84 films exhibit a relatively high crystallization temperature of ~250 °C, excelling in long data retention. In addition, a large optical contrast exists between the amorphous and crystalline states, which may make it suitable for use in optical discs. Molecular dynamics simulations indicate that a unique local structure order in the amorphous and crystalline phases is responsible for the optical properties observed in the experiment. The similarity found in the short-range orders of the amorphous and crystalline phases is beneficial to better understanding the fast phase transition of phase-change memory.

The benefits of platinum-based chemotherapy (PBC) on survival of esophageal squamous cell carcinoma (ESCC) patients are inexplicit due to the varied therapeutic effects. Nucleotide excision repair (NER) pathway plays a vital role in removing platinum-DNA adducts in tumor cells and hence may modulate the therapeutic effect and survival outcome. The present study assessed the associations of 26 potentially functional regulatory single nucleotide polymorphisms (rSNPs) in nine core NER genes with disease-free survival (DFS) and overall survival (OS) in 339 ESCC patients. We found that ERCC2 rs2097215 T and rs3916788 A, ERCC5 rs3759497 A and XPC rs3731054 C alleles were associated with unfavorable DFS. Patients carrying high-risk allele group (HRG, 5-8 risk alleles) had a significantly shorter DFS, compared with those carrying low-risk alleles (LRG, 0-4 risk alleles) [adjusted hazards ratio (HRadj ) = 1.64, 95%CI = 1.23-2.19, Padj

To retrospectively assess the clinicopathological characteristics of orbital granular cell tumours (GCTs).A non-comparative review of the clinical characteristics, imaging, histopathological features, management, and prognosis of five cases of benign GCT and one case of malignant GCT (MGCT) was conducted, along with a review of the English language literature.Among the six cases, four tumours were adherent to the extraocular muscle (EOM), and three tumours to the optic nerve (ON). Morphologic examinations revealed polygonal cells containing periodic-acid-Schiff-positive eosinophilic granules. All tumours (100%) were positive for VIM and NSE, five (83.3%) tumours were positive for S-100, and three (50%) tumours were positive for CD68. The follow-up examination of the MGCT witnessed recurrence and brain metastasis despite several thorough resections, but the patient remained alive; the follow-up examination of the four benign GCTs that had received incomplete excision revealed recurrence in one patient and dramatic shrinkage of the residual tumour in another; there was no recurrence in the other two patients.GCT should be considered in the differential diagnosis of orbital tumours, which may affect EOMs and ON. The natural course of GCT can include tumour progression, stability, or spontaneous regression. To avoid recurrence, complete resection is recommended for orbital GCT. To the best of our knowledge, primary orbital MGCT is reported for the first time.

A new solid-state polymer composite electrolyte based on hypergrafted nano-silica (SiO2-g-HBPAE)/hyperbranched poly (amine-ester) (HBPAE) doped with lithium perchlorate (LiClO4) was studied in this paper. The N,N-diethylol-3-amine-2-methyl methylpropionate monomer was firstly synthesized by methyl methacrylate (MMA) and diethanolamine through Michael addition reaction and then self-condensed on the surface of nano-silica pretreated by 3-aminopropyltriethoxysilane (APTES) and MMA. The synthetic procedure of the monomers and SiO2-g-HBPAE/HBPAE was traced by fluorescence spectra. The size and grafting ratio of SiO2-g-HBPAE were characterized by transmission electron microscopy, static light scattering and thermogravimetric analysis. Incorporating SiO2-g-HBPAE to HBPAE could not only decrease the glass transition temperature of polymer according to the differential scanning calorimetry characterization, but also increase the elastic and viscosity modules indicated by rheological measurement results. Electrochemical properties of SiO2-g-HBPAE/HBPAE/LiClO4 were also investigated. The conductivity of SiO2-g-HBPAE/HBPAE with 50 wt% LiClO4 reached 1.4 × 10−5 S/cm at 30 °C and 10−3 S/cm at 100 °C. The lithium-ion transference number of synthesized hyperbranched electrolyte can be up to 0.55.

The multilevel impurity photovoltaic effect (IPV) of the sulfur doped crystalline silicon (c-Si) is studied by using the SCAPS program. The effects of impurity concentration (Nt) of two and four defect levels on the performance of sulfur doping c-Si solar cell are investigated, respectively. Then, the quantum efficiencies (QE) of different cases (without impurity, two and four defect levels) are considered. The results show that after the doping of sulfur, the infrared response of the c-Si solar cell is enhanced. Moreover, the infrared response wavelength range of the case considering two defect levels may be wider than that of four defect levels. In order to get the highest photovoltaic conversion efficiency (PCE), the number and the type of defect levels should be controlled. In the end, with four defect levels considered, the thickness and background doping concentration (ND for the n-type layer and Na for the p-type layer) of each layer of the n þ epep þ structure are optimized. Our results suggest that higher PCE could be achieved than that without impurity by choosing a suitable doping concentration. The efficiency of 25.32% attained in the four-defect case improved the PCE by 2% more than the value of 23.22% without sulfur doping.

Atomic-scale simulations are performed to study atomic motion on Cu surfaces to illustrate the effect of the scanning tunneling microscopy tip on mass transport (MT) in the surfaces and on top of the Co island in heteroepitaxial Co/Cu(0 0 1) and Co/Cu(1 1 1) systems. First we investigate tip-induced atomic motion of Co atoms embedded in the Cu(0 0 1) surface at zero bias voltage. With the help of the tip, the Co atom in the surface can freely diffuse toward its nearby vacancy site. So-called vacancy mechanism is used to interpret this phenomenon. Then tip-mediated atomic motion of Co adatoms on the Co islands supported by a Cu(1 1 1) surface is studied. It is revealed that the tip has a significant effect on the diffusion of adatoms on the islands and interlayer mass transport at the island edge. Interlayer mass transport at the island edge is found to depend strongly on the tip height and the lateral distance from the tip. By calculating the diffusion barriers, it is found that the jumping diffusion barrier on the island can be zero by the tip vertical manipulation while the Ehrlich–Schwoebel diffusion barrier at the island edge can be reduced by the tip lateral manipulation. Thus, the quality of thin films can be improved by controlling MT in and/or on the surface.