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

D-Glycero-D-mannno-heptose 1β, 7-bisphosphate (HBPβ) is an important intermediate for constructing the core structure of Gram-negative bacterial lipopolysaccharides and was reported as a pathogen-associated molecular pattern (PAMP) that regulates immune responses. HBPβ with 3-O-amyl amine linker and its monophosphate derivative D-glycero-D-mannno-heptose 7-phosphate (HP) with 1α-amyl amine linker have been synthesized as candidates for immunity study of HBPβ. The O3-amyl amine linker of heptose was installed by dibutyltin oxide-mediated regioselective alkylation under fine-tuned protecting condition. The stereoselective installation of 1β-phosphate ester was achieved by NIS-mediated phosphorylation at low temperature. The strategy for installation of 3-O-amyl amine linker onto HBP derivative can be expanded to the syntheses of other conjugation-ready carbohydrates bearing anomeric phosphoester.

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.

OBJECTIVE： To investigate the effects of Buyang huanwu decoction on the expression of MMPs and TIMPs in cardiac tissue of viral myocarditis （VMC） model mice. METHODS： Male BALb/c mice were randomly divided into control group， model group， positive control group [captopril， 100 mg/（kg·d）]， Buyang huanwu decoction low-dose， medium-dose and high-dose groups [6， 18， 36 g/（kg·d）]， with 24 mice in each group. Except for control group， other groups were given Coxsackie virus B3 once intraperitoneally to induce VMC model. After modeling， control group and model group were given constant volume of normal saline intragastrically； administration groups were given relevant medicine intragastrically； once a day， for consecutive 30 days. The general situation of mice in each group was observed. The day of inoculation was set at 0 d， heart mass to body mass ratio （HW/BW） was measured at 4， 10， 20， 30 d after inoculation. The morphological characteristics of myocardium were observed by HE staining， and the myocardial histopathological scores of myocardium were evaluated. The distribution of type Ⅰ and Ⅲ collagen in myocardium was observed by Abcam picrosirius red staining， and the ratio of type Ⅰ to Ⅲ collagen was calculated. At 30 d， relative expressions of MMP-1， MMP-3， MMP-9 and TIMP-1 in cardiac tissue were detected by Western blotting assay， and the ratio of MMPs to TIMPs was calculated. RESULTS： Compared with control group， mice in model group suffered from irritability， arch back， alleviation of stimulation response， reduction of body mass and even mental depression. Typical inflammatory changes and local interstitial hyperemia were observed in the myocardium， accompanied by a large number of lymphocyte infiltration and distribution of type Ⅰ and Ⅲ collagen. HW/BW （at different time points of 10-30 d）， myocardial histopathological score （at different time points of 4-30 d）， ratio of type Ⅰ and Ⅲ collagen （at different time points of 4-30 d）， the expression of MMP-1 and MMP-9， ratio of MMPs to TIMPs were increased significantly， while the expression of MMP-3 and TIMP-1 were decreased significantly （P＜0.05）. Compared with model group， above symptoms of mice in administration groups were improved to different extents. HW/BW [at different time points of 10-30 d in administration groups （except for 10 d in Buyang huanwu decoction low-dose group）]， myocardial histopathological score （at different time points of 10-30 d in administration groups）， ratio of type Ⅰand Ⅲ collagen （at different time points of 4-10 d in positive control group and Buyang huanwu decoction high-dose group， at different time points of 20-30 d in Buyang huanwu decoction low-dose and medium-dose groups）， the expression of MMP-1 （positive control group and Buyang huanwu decoction high-dose group） and MMP-9 （administration groups）， ratio of MMPs to TIMPs （administration groups） were decreased significantly， while the expression of MMP-3 （positive control group， Buyang huanwu decoction low-dose and high-dose groups） and TIMP-1 （administration groups） were increased significantly （P＜0.05）. CONCLUSIONS： Buyang huanwu decoction can inhibit myocardial fibrosis of VMC model mice by inhibiting myocardial collagen hyperplasia， regulating the expression of MMPs and TIMPs， improving MMPs/TIMPs imbalance.

The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
Adalimumab ; Asia ; Asian Continental Ancestry Group ; Biological Factors ; Biosimilar Pharmaceuticals ; Colitis ; Colitis, Ulcerative ; Consensus ; Cooperative Behavior ; Crohn Disease ; Gastroenterology ; Hepatitis B ; Humans ; Immunologic Factors ; Inflammatory Bowel Diseases ; Infliximab ; Pharmacogenetics ; Philippines ; Practice Guidelines as Topic ; Tuberculosis ; Ulcer

Objective: To investigate frailty progress status and related factors in the elderly living in communities. Methods: A cohort of elderly people aged 65 and over in Pingyi community of Dujiangyan, Sichuan province, was established. Face-to-face questionnaire survey was conducted by trained interviewers. The frailty status, cognitive function, nutrition status and other functions of the subjects surveyed were evaluated at baseline survey and during follow-up. The socio-demographic and clinical characteristics of the subjects surveyed were assessed at baseline survey. Binary logistic regressions were used to identify factors associated with frailty progress. Results: A total of 653 elderly people were surveyed in January 2014, and 507 elderly people were followed up while 146 elderly people terminated further follow-up in January 2017. The prevalence rates of frailty and pre-frailty at baseline survey were 11.2% (n=57) and 26.2% (n=133), respectively. After 3 years, 205 subjects (40.4%) surveyed experienced frailty progress, 276 (54.5%) remained to be in frailty state at baseline survey, and 26 (5.1%) had improvement. Disability (OR=8.27, 95%CI: 1.62-42.26), visual problem (OR=2.02, 95%CI: 1.27-3.22), cognitive impairment (OR=1.94, 95%CI: 1.08-3.48), poor self-rated health (OR=1.89, 95%CI: 1.07-3.31), chronic pain (OR=1.57, 95%CI: 1.03-2.40) and older age (OR=1.12, 95%CI: 1.08-1.17) were independently associated with the progress of frailty. In contract, overweight was a protective factor (OR=0.54, 95%CI: 0.34-0.85). Conclusions: Frailty is a dynamic syndrome affected by several socio-demographic factors and geriatric factors. The results of the study can be used in the prevention of frailty progress in the elderly in communities.
Aged ; Aged, 80 and over ; China/epidemiology* ; Frail Elderly/statistics & numerical data* ; Frailty ; Geriatric Assessment/statistics & numerical data* ; Humans ; Prospective Studies ; Quality of Life/psychology* ; Surveys and Questionnaires

Adult ; Antitubercular Agents ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Pneumonia ; drug therapy ; etiology ; Retrospective Studies ; Treatment Outcome ; Tuberculosis, Multidrug-Resistant ; complications ; drug therapy

Due to the complex circuitry and plethora of cell types involved in somatosensation, it is becoming increasingly important to be able to observe cellular activity at the population level. In addition, since cells rely on an intricate variety of extracellular factors, it is important to strive to maintain the physiological environment. Many electrophysiological techniques require the implementation of artificially-produced physiological environments and it can be difficult to assess the activity of many cells simultaneously. Moreover, imaging Ca transients using Ca-sensitive dyes often requires in vitro preparations or in vivo injections, which can lead to variable expression levels. With the development of more sensitive genetically-encoded Ca indicators (GECIs) it is now possible to observe changes in Ca transients in large populations of cells at the same time. Recently, groups have used a GECI called GCaMP to address fundamental questions in somatosensation. Researchers can now induce GCaMP expression in the mouse genome using viral or gene knock-in approaches and observe the activity of populations of cells in the pain pathway such as dorsal root ganglia (DRG), spinal neurons, or glia. This approach can be used in vivo and thus maintains the organism's biological integrity. The implementation of GCaMP imaging has led to many advances in our understanding of somatosensation. Here, we review the current findings in pain research using GCaMP imaging as well as discussing potential methodological considerations.
Afferent Pathways ; physiology ; Animals ; Calcium ; metabolism ; Calcium Signaling ; drug effects ; genetics ; Ganglia, Spinal ; metabolism ; Humans ; Pain ; metabolism ; pathology

Asthma ; therapy ; Humans ; Patient Education as Topic ; Physician-Patient Relations ; Self Care

Family-based cohort study is a special type of study design, in which biological samples and environmental exposure information of the member in a family are collected and related follow up is conducted. Family-based cohort study can be applied to explore the effect of genetic factors, environmental factors, gene-gene interaction, and gene-environment interaction in the etiology of complex diseases. This paper summarizes the objectives, methods and results, as well as the opportunities and challenges of the family-based cohort study on common chronic non-communicable diseases in rural population in northern China.
China/epidemiology* ; Chronic Disease/ethnology* ; Cohort Studies ; Female ; Gene-Environment Interaction ; Humans ; Male ; Middle Aged ; Noncommunicable Diseases/ethnology* ; Research Design ; Rural Population