Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Cholangiocarcinoma/pathology* ; Carcinoma, Squamous Cell ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/pathology*

Humans ; B7-H1 Antigen ; Neoplasms/genetics*

<b>Objective:b> To investigate the clinical outcome and preventive effect of polyetheretherketone(PEEK) rod hybrid surgery on proximal junction failure(PJF) after long-segment fusion of adult spinal deformity. <b>Methods:b> A retrospective study was conducted to analyze patients with degenerative scoliosis/kyphosis who underwent long-segment decompression and fusion surgery at Department of Orthopedics, Peking University First Hospital from January 2017 to December 2021. A total of 75 patients were included in the study, including 14 males and 61 females, aged (67.2±6.8)years (range:55 to 84 years). According to the operation method chosen by the patients, the patients were divided into PEEK rod hybrid group (20 cases) and traditional titanium rod group (55 cases). The general information of the patients was collected, and the coronal and sagittal parameters of the spine were measured before operation, at 1 month after operation, and at the last follow-up. The clinical effect of surgery was judged by the visual analogue scale (VAS) and Oswestry disability index (ODI). Whether proximal junctional kyphosis (PJK) and PJF occurred during the follow-up and the time of occurrence were recorded. Comparisons between groups were performed using independent sample t test, Mann-Whitney U test, χ² test and Fisher's exact probability method. The data before and after surgery in the same group were compared using the paired sample t test and the Wilcoxon test. <b>Results:b> There were no significant differences in age, gender, body mass index, bone mineral density, distal instrumented vertebrae, surgical segments, osteotomy method, operation time, and intraoperative bleeding between the two groups (all P>0.05). The follow-up time of the PEEK rod group was shorter(M(IQR)16.5(4.8) vs. 25.0(12.0),Z=-4.230,P<0.01). There were no significant differences in coronal, sagittal parameters, VAS and ODI between the two groups before operation (all P>0.05). Postoperative coronal Cobb angle, pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis, sagittal vertical axis (SVA), VAS and ODI were significantly improved in both groups(all P<0.05). At the last follow-up, the SVA of the PEEK rod hybrid group was(3.74±2.40)cm, which was significantly lower than that of the titanium rod group (6.28±4.06)cm (t'=-3.318, P=0.002). At the last follow-up, the ODI of the PEEK rod hybrid group was 30.7±6.1, significantly better than the titanium rod group 39.3±17.2(t=-3.203, P=0.046). PJK occurred in 2 patients (10.0%) in the PEEK rod hybrid group, and no PJF phenomenon was observed. In the titanium rod group, 18 patients (32.7%) developed PJK, and 11 patients (20.0%) developed PJF. There was a statistically significant difference in the incidence of PJF between the PEEK rod hybrid group and the titanium rod group (P=0.031). <b>Conclusions:b> PEEK rod hybrid surgery can achieve good clinical results in the treatment of adult spinal deformities. Compared with traditional titanium rod surgery, it can significantly reduce the incidence of postoperative PJF and improve the clinical function of patients.
Male ; Female ; Animals ; Humans ; Adult ; Retrospective Studies ; Titanium ; Kyphosis/etiology* ; Sacrum ; Osteotomy/adverse effects* ; Spinal Fusion/methods* ; Lumbar Vertebrae ; Treatment Outcome ; Postoperative Complications/epidemiology*

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Squamous Cell/genetics* ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide

Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Hearing Loss, Noise-Induced ; Humans ; Male ; MicroRNAs ; Noise, Occupational ; Polymorphism, Single Nucleotide ; STAT3 Transcription Factor

Adult ; Automobiles ; Hearing Loss, High-Frequency ; Hearing Loss, Noise-Induced/etiology* ; Humans ; Male ; Noise, Occupational/adverse effects* ; Occupational Diseases ; Occupational Exposure

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

As next-generation sequencing (NGS) technology has become widely used to identify genetic causal variants for various diseases and traits, a number of packages for checking NGS data quality have sprung up in public domains. In addition to the quality of sequencing data, sample quality issues, such as gender mismatch, abnormal inbreeding coefficient, cryptic relatedness, and population outliers, can also have fundamental impact on downstream analysis. However, there is a lack of tools specialized in identifying problematic samples from NGS data, often due to the limitation of sample size and variant counts. We developed SeqSQC, a Bioconductor package, to automate and accelerate sample cleaning in NGS data of any scale. SeqSQC is designed for efficient data storage and access, and equipped with interactive plots for intuitive data visualization to expedite the identification of problematic samples. SeqSQC is available at http://bioconductor.org/packages/SeqSQC.
Breast Neoplasms ; genetics ; Cohort Studies ; Continental Population Groups ; genetics ; Female ; Genome, Human ; High-Throughput Nucleotide Sequencing ; methods ; standards ; Humans ; Software ; Whole Exome Sequencing

<b>Objective:b> To describe the genetic structure of populations in different areas of China, and explore the effects of different strategies to control the confounding factors of the genetic structure in cohort studies. <b>Methods:b> By using the genome-wide association study (GWAS) on data of 4 500 samples from 10 areas of the China Kadoorie Biobank (CKB), we performed principal components analysis to extract the first and second principal components of the samples for the component two-dimensional diagram generation, and then compared them with the source of sample area to analyze the characteristics of genetic structure of the samples from different areas of China. Based on the CKB cohort data, a simulation data set with cluster sample characteristics such as genetic structure differences and extensive kinship was generated; and the effects of different analysis strategies including traditional analysis scheme and mixed linear model on the inflation factor (λ) were evaluated. <b>Results:b> There were significant genetic structure differences in different areas of China. Distribution of the principal components of the population genetic structure was basically consistent with the geographical distribution of the project area. The first principal component corresponds to the latitude of different areas, and the second principal component corresponds to the longitude of different areas. The generated simulation data showed high false positive rate (λ=1.16), even if the principal components of the genetic structure was adjusted or the area specific subgroup analysis was performed, λ could not be effectively controlled (λ>1.05); while, by using a mixed linear model adjusting for the kinship matrix, λ was effectively controlled regardless of whether the genetic structure principal component was further adjusted (λ=0.99). <b>Conclusions:b> There were large differences in genetic structure among populations in different areas of China. In molecular epidemiology studies, bias caused by population genetic structure needs to be carefully treated. For large cohort data with complex genetic structure and extensive kinship, it is necessary to use a mixed linear model for association analysis.
China ; Genetic Structures ; Genome-Wide Association Study ; Humans ; Linear Models ; Principal Component Analysis

<b>Objective:b> To examine the prevalence of 'healthy lifestyle' from data extracted from the China Kadoorie Biobank (CKB) of 0.5 million adults from ten areas across China. <b>Methods:b> After excluding participants with self-reported histories of coronary heart disease, stroke or cancer, a total of 487 198 participants at baseline (2004-2008) and 22 604 participants at second survey (2013- 2014), were included for analysis. 'Healthy lifestyle' was defined as haing the following characteristics: a) never smoking or having stopped smoking for reasons other than illness; b) alcohol drinking <25 g/day (men)/<15 g/day (women); c) diet rich in vegetables, fruits, legumes and fish, but low in red meat; d) upper quarter of the physical activity level; e) body mass index of 18.5-23.9 kg/m(2) and waist circumstance <85 cm (men)/80 cm (women). We calculated the healthy lifestyle scores (HLS) by counting the number of all the healthy lifestyle factors, with a range from 0 to 6. <b>Results:b> At baseline, prevalence rates of the above five healthy lifestyles (except physical activity) were 70.6%, 92.6%, 8.7%, 52.6% and 59.0%, respectively, with the mean HLS being 3.1±1.2. Most participants (81.4%) had2-4 healthy components, while only 0.7% (0.2% in men and 1.0% in women) of all the participants had all six healthy lifestyles. Participants who were women, at younger age, with more schooling and rural residents, were more likely to adhere to the healthy lifestyle. After ten years, the mean HLS showed a slight decrease. <b>Conclusion:b> The prevalence of optimal lifestyles in Chinese adults appeared extremely low. Levels of 'healthy lifestyle' varied greatly among those populations with different socio-demographic characteristics across the ten areas in China.
Adult ; Asian People/statistics & numerical data* ; China ; Female ; Healthy Lifestyle ; Humans ; Life Style ; Male ; Prevalence ; Risk Factors