YAP1 inhibits the senescence of alveolar epithelial cells by targeting Prdx3 to alleviate pulmonary fibrosis.

The senescence of alveolar type II (AT2) cells impedes self-repair of the lung epithelium and contributes to lung injury in the setting of idiopathic pulmonary fibrosis (IPF). Yes-associated protein 1 (YAP1) is essential for cell growth and organ development; however, the role of YAP1 in AT2 cells during pulmonary fibrosis is still unclear. YAP1 expression was found to be downregulated in the AT2 cells of PF patients. Deletion of YAP1 in AT2 cells resulted in lung injury, exacerbated extracellular matrix (ECM) deposition, and worsened lung function. In contrast, overexpression of YAP1 in AT2 cells promoted alveolar regeneration, mitigated pulmonary fibrosis, and improved lung function. In addition, overexpression of YAP1 alleviated bleomycin (BLM) -induced senescence of alveolar epithelial cells both in vivo and in vitro. Moreover, YAP1 promoted the expression of peroxiredoxin 3 (Prdx3) by directly interacting with TEAD1. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in BLM-treated MLE-12 cells, whereas depletion of Prdx3 partially abrogated the protective effect of YAP1. Furthermore, overexpression of Prdx3 facilitated self-repair of the injured lung and reduced ECM deposition, while silencing Prdx3 attenuated the antifibrotic effect of YAP1. In conclusion, this study demonstrated that YAP1 alleviates lung injury and pulmonary fibrosis by regulating Prdx3 expression to improve mitochondrial dysfunction and block senescence in AT2 cells, revealing a potential novel therapeutic strategy for pulmonary fibrosis.

BertNDA: A Model Based on Graph-Bert and Multi-Scale Information Fusion for ncRNA-Disease Association Prediction.

Non-coding RNAs (ncRNAs) are a class of RNA molecules that lack the ability to encode proteins in human cells, but play crucial roles in various biological process. Understanding the interactions between different ncRNAs and their impact on diseases can significantly contribute to diagnosis, prevention, and treatment of diseases. However, predicting tertiary interactions between ncRNAs and diseases based on structural information in multiple scales remains a challenging task. To address this challenge, we propose a method called BertNDA, aiming to predict potential relationships between miRNAs, lncRNAs, and diseases. The framework identifies the local information through connectionless subgraph, which aggregate neighbor nodes' feature. And global information is extracted by leveraging Laplace transform of graph structures and WL (Weisfeiler-Lehman) absolute role coding. Additionally, an EMLP (Element-wise MLP) structure is designed to fuse pairwise global information. The transformer-encoder is employed as the backbone of our approach, followed by a prediction-layer to output the final correlation score. Extensive experiments demonstrate that BertNDA outperforms state-of-the-art methods in prediction assignment and exhibits significant potential for various biological applications. Moreover, we develop an online prediction platform that incorporates the prediction model, providing users with an intuitive and interactive experience. Overall, our model offers an efficient, accurate, and comprehensive tool for predicting tertiary associations between ncRNAs and diseases.

Influence of Obesity and Changes in Weight or BMI on Incident Fractures in Postmenopausal Women: From Peking Vertebral Fracture Study.

This study aims to investigate the influence of overweight/obesity and change in weight or body mass index (BMI) on incident fractures among Chinese postmenopausal women. According to BMI, 754 postmenopausal women were categorized into normal weight (NW), overweight (OW), and obesity (OB) groups, respectively. We used data from the baseline and the second survey for statistical analysis, including anthropometric data, clinical fractures, and morphometric vertebral fractures (MVFs) assessed by X-rays. The prevalence of previous MVFs was 32.7% and 21.8% in the OB and NW groups, respectively (p < 0.05). All incident fractures and incident MVFs accounted for 10.7 and 6.3% among all participants within five years. Overweight/obesity and increase in weight or BMI during the follow-up had no associations with all incident fractures, incident MVFs, and incident clinical non-VFs among all participants. However, after multivariate adjustment, the increased BMI at baseline was the risk factor of incident MVFs in the OW group (odds ratio, OR 2.06, 95% confidence interval, 95% CI 1.16-3.66, p = 0.014), and increase in weight (OR 0.89, 95% CI 0.79-0.99, p = 0.036) or BMI (OR 0.77, 95% CI 0.59-0.99, p = 0.045) during the follow-up were the protective factors of all incident fractures in the NW group. Overweight/obesity and change in weight or BMI do not correlate with fracture risk in postmenopausal women, but an increase in weight is the protective factor against incident fractures in normal-weight participants. Overweight postmenopausal women with a higher BMI should pay attention to the risk of MVFs.

Incident vertebral fracture and longitudinal BMD change in Chinese postmenopausal women with early CKD: Peking Vertebral Fracture Study.

Early chronic kidney disease (CKD) and non-CKD individuals had similar morphometric vertebral fracture (mVF) incidence and longitudinal bone mineral density (BMD) change. CKD did not modify the association between BMD and incident mVF status. Patients with a higher baseline BMD had a higher longitudinal BMD loss in early CKD. PURPOSE: The aim of this 5-year longitudinal cohort study was to compare the risk of incident morphometric vertebral fracture (mVF) and longitudinal bone mineral density (BMD) change between individuals with early chronic kidney disease (CKD) and those without CKD. METHODS: A total of 869 Chinese postmenopausal women were enrolled in the study. Serum creatinine levels were assessed using standard methods, and estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Incident mVF was confirmed through lateral radiographs of the thoracolumbar spine. BMDs at the lumbar spine (LS) and femoral neck (FN) were measured using dual-energy X-ray absorptiometry. CKD was defined based on eGFR values: 60-89 mL/min/1.73m2 for stage 2 (n = 511) and 30-59 mL/min/1.73m2 for stage 3 (n = 92). The non-CKD group included individuals with an eGFR greater than or equal to 90 mL/min/1.73m2. RESULTS: The incidence of mVF was not statistically different between individuals with early CKD and those without CKD (4.1% in non-CKD, 6.3% in CKD stage 2, and 7.6% in CKD stage 3; p = 0.348). Neither eGFR nor CKD status was significantly associated with incident mVF in the multivariate logistic regression analysis. Baseline BMD T-scores were negatively associated with incident mVF (LS T-score, OR = 0.603, 95% CI = 0.468-0.777; FN T-score, OR = 0.511, 95% CI = 0.350-0.746). No evidence of interaction between BMD T-scores and CKD status were identified (p = 0.284-0.785) . The differences in longitudinal BMD changes between non-CKD and CKD groups were comparable (FN BMD: -6.31 ± 7.20% in non-CKD, -5.07 ± 8.20% in CKD stage 2, and -4.49 ± 8.40% in CKD stage 3, p = 0.556; LS BMD: -1.38 ± 8.18% in non-CKD, -0.32 ± 7.14% in CKD stage 2, and 1.5 ± 6.97% in CKD stage 3, p = 0.406). Individuals with a higher baseline FN BMD showed a greater longitudinal FN BMD loss (r = -0.185, p < 0.001) . CONCLUSIONS: Our study revealed that early CKD was not associated with an increased risk of incident mVF or greater longitudinal BMD loss. Moreover, CKD did not modify the association between BMD and the risk of incident mVF, suggesting that the management and prevention of fractures in early CKD should be approached similarly to those without CKD. Measurement of BMD appears to be crucial for predicting incident mVF risk and longitudinal bone loss in early CKD.

KGETCDA: an efficient representation learning framework based on knowledge graph encoder from transformer for predicting circRNA-disease associations.

Recent studies have demonstrated the significant role that circRNA plays in the progression of human diseases. Identifying circRNA-disease associations (CDA) in an efficient manner can offer crucial insights into disease diagnosis. While traditional biological experiments can be time-consuming and labor-intensive, computational methods have emerged as a viable alternative in recent years. However, these methods are often limited by data sparsity and their inability to explore high-order information. In this paper, we introduce a novel method named Knowledge Graph Encoder from Transformer for predicting CDA (KGETCDA). Specifically, KGETCDA first integrates more than 10 databases to construct a large heterogeneous non-coding RNA dataset, which contains multiple relationships between circRNA, miRNA, lncRNA and disease. Then, a biological knowledge graph is created based on this dataset and Transformer-based knowledge representation learning and attentive propagation layers are applied to obtain high-quality embeddings with accurately captured high-order interaction information. Finally, multilayer perceptron is utilized to predict the matching scores of CDA based on their embeddings. Our empirical results demonstrate that KGETCDA significantly outperforms other state-of-the-art models. To enhance user experience, we have developed an interactive web-based platform named HNRBase that allows users to visualize, download data and make predictions using KGETCDA with ease. The code and datasets are publicly available at https://github.com/jinyangwu/KGETCDA.

Long non-coding RNA PFI inhibits apoptosis of alveolar epithelial cells to alleviate lung injury via miR-328-3p/Creb1 axis.

Acute lung injury (ALI), a common clinical type of critical illness, is an acute hypoxic respiratory insufficiency caused by the damage of alveolar epithelial cells and capillary endothelial cells. In a previous study, we reported a novel lncRNA, lncRNA PFI, which could protect against pulmonary fibrosis in pulmonary fibroblasts. The present study demonstrated that lncRNA PFI was downregulated in alveolar epithelial cell of mice injury lung tissues, and further investigated the role of lncRNA PFI in regulating inflammation-induced alveolar epithelial cell apoptosis. Overexpression of lncRNA PFI could partially abrogated bleomycin induced type II AECs injured. Subsequently, bioinformatic prediction revealed that lncRNA PFI might directly bind to miR-328-3p, and further AGO-2 RNA binding protein immunoprecipitation (RIP) assay confirmed their binding relationship. Furthermore, miR-328-3p promoted apoptosis in MLE-12 cells by limiting the activation of the Creb1, a protein correlated with cell apoptosis, whereas AMO-328-3p ablated the pro-apoptosis effect of silencing lncRNA PFI in MLE-12 cells. While miR-328-3p could also ablate the function of lncRNA PFI in bleomycin treated human lung epithelial cells. Enhanced expression of lncRNA PFI reversed the LPS-induced lung injury in mice. Overall, these data reveal that lncRNA PFI mitigated acute lung injury through miR-328-3p/Creb1 pathway in alveolar epithelial cells.

Surface Feature Prediction for Laser Ablated 40Cr13 Stainless Steel Based on Extreme Learning Machine.

Determining an optimal combination of laser process parameters can significantly improve the efficiency and quality of 40Cr13 steel surface processing. In this study, two machine learning models (ELMSS and ELMPS) were proposed to predict the processing results of surface features to optimize process parameters. The prediction accuracies of the proposed models were always higher than those of traditional back propagation (BP) and radial basis function (RBF) neural networks, and the calculation time of the proposed models was significantly reduced. In comparison, the prediction accuracy ranking for ablation depth was ELMSS (92.6%), BP (89.8%), and RBF (89.6%), and for the ablation width, it was ELMSS (98.3%), BP (97.4%), and RBF (96.1%). The material removal rate was 92.4%, 91.1%, and 89.1% for ELMSS, BP, and RBF, respectively. Finally, the prediction accuracy ranking for surface roughness was 86.8%, 80.7%, and 79.5% for ELMPS, BP, and RBF, respectively. After optimization by the genetic algorithm, the prediction accuracies of the proposed models for the depth, width, material removal rate, and surface roughness reached 94.0%, 99.0%, 93.2%, and 91.2%, respectively. With the support of ELMSS and ELMPS, the results of the surface features can be predicted before machining and the appropriate process parameters can be selected in advance.

Research Status and Prospect of Laser Scribing Process and Equipment for Chemical Milling Parts in Aviation and Aerospace.

Laser scribing in chemical milling is an important process which can effectively improve the precision and efficiency of chemical milling, and is of great significance to improve the thrust-weight ratio and manufacturing efficiency of aviation and aerospace parts. According to the scribing requirements in chemical milling for aviation and aerospace parts, the process and mechanism of laser scribing were studied and the influence of different process parameters for the quality of laser scribing was analyzed. Based on the review of related research literature, the laser scribing process, the ablation mechanism and technology of different materials and the selective laser removal process for "laser-coating-substrate" are summarized and discussed. Based on the requirements of high-precision laser scribing on complex surfaces, the current situation of laser scribing equipment is summarized. Finally, the practical challenges and key technical problems for the laser scribing process are summarized, and the application and development of laser scribing in aerospace manufacturing are prospected.

Design, Synthesis and Antimicrobial Evaluation of Novel Benzimidazoleincorporated Naphthalimide Derivatives as Salmonella typhimurium DNA Intercalators, and Combination Researches.

OBJECTIVE: A series of novel benzimidazole-incorporated naphthalimide derivatives were designed and prepared in an effort to overcome the increasing antibiotic resistance. METHODS: The target novel benzimidazole-incorporated naphthalimide derivatives were synthesized from commercial 4-bromo-1,8-naphthalic anhydride and o-phenylene diamine by aminolysis, Nalkylation and so on. The antimicrobial activity of the synthesized compounds was evaluated in vitro by a two-fold serial dilution technique. The interaction of compound 10g with Salmonella typhimurium DNA was studied using UV-vis spectroscopic methods. RESULTS: Compound 10g bearing a 2,4-dichlorobenzyl moiety exhibited the best antimicrobial activities in this series relatively; especially, it exhibited comparable activity against Salmonella typhimurium in comparison with the reference drug Norfloxacin (MIC = 4 µg/mL). Further research showed that compound 10g could effectively intercalate into the Salmonella typhimurium DNA to form the 10g-DNA complex, which might correlate with the inhibitory activity. Molecular docking results demonstrated that naphthalimide compound 10g could interact with base-pairs of DNA hexamer duplex by π-π stacking. Additionally, the combination of the strong active compound with clinical drugs exhibited better antimicrobial efficiency with less dosage and broader antimicrobial spectrum than the separate use of them alone. Notably, these combined systems were more sensitive to Fluconazole-insensitive M. ruber. CONCLUSION: This work provides a promising starting point to optimize the structures of benzimidazole- incorporated naphthalimide derivatives as potent antimicrobial agents.

Associations between Osteocalcin, Calciotropic Hormones, and Energy Metabolism in a Cohort of Chinese Postmenopausal Women: Peking Vertebral Fracture Study.

OBJECTIVE: The endocrine function of bone in energy metabolism may be mediated by the osteocalcin (OC). We examined the association between OC and energy metabolism among Chinese postmenopausal women. Design and Setting. A cross-sectional cohort study enrolling 1635 participants was conducted using data from the Peking Vertebral Fracture study. Partial correlation analysis was performed to explore the correlation of OC, parathyroid hormone (PTH), or 25-hydroxyvitamin D (25(OH)D) with glycemic and lipid metabolic parameters. A logistic regression model was used to investigate the association of OC, PTH, or 25(OH)D with the prevalence of diabetes and dyslipidemia. RESULTS: Serum levels of OC, PTH, and 25(OH)D were all positively correlated with serum cholesterol levels, whereas only OC was negatively associated with serum glucose level. In the logistic regression model, both OC and PTH were negatively associated with the prevalence of diabetes (odds ratio [OR], 95% confidence interval [95% CI]: 0.967, 0.948-0.986 for OC and 0.986, 0.978-0.994 for PTH). No significant association was found between 25(OH)D and diabetes. Both OC and 25(OH)D, rather than PTH, were associated with abnormalities of high cholesterol levels, such as hypercholesterolemia and high LDL-C levels. Further classifying the population based on the median value of OC and PTH, low OC and low PTH subgroup had the highest OR, 95% CI for diabetes (1.873, 1.287-2.737) and the lowest OR, 95% CI for hypercholesterolemia (0.472, 0.324-0.688) and for high LDL-C (0.538, 0.376-0.771). CONCLUSION: Among Chinese postmenopausal women, a lower serum level of OC was associated with a higher prevalence of diabetes and lower serum cholesterol levels, and a low PTH concentration could magnify these associations.

Incident Fracture Risk in Type 2 Diabetic Postmenopausal Women in Mainland China: Peking Vertebral Fracture Study.

Using data from the Peking Vertebral Fracture Study, we conducted a longitudinal cohort study to investigate the association between type 2 diabetes mellitus (T2DM) and the risk of incident fractures, especially of vertebral fractures (VFs), and we also examined the modifying effect of body mass index (BMI) on this association and the effect of bone mineral density (BMD) T-score as a risk factor for incident fractures in T2DM. Chinese postmenopausal women were enrolled (n = 982), among whom 186 had T2DM. Incident VFs were confirmed by lateral radiographs of the thoracolumbar spine (T4-L5), while incident clinical non-VFs were self-reported. BMDs at the lumbar spine (LS) and femoral neck (FN) were measured by dual-energy X-ray absorptiometry. T2DM and non-DM women were at similar risk for VFs (OR 0.74, 95% CI 0.32-1.74), even adjusting for age, BMI, BMD, and previous fractures. Meanwhile, T2DM women had nearly twice the risk for non-VFs (HR 1.95, 95% CI 1.11-3.35) compared with non-DM women. After stratifying by BMI, the risk of VFs remained similar between diabetics and non-diabetics despite their BMI status (p for interaction = 0.470), and the risk of non-VFs was positively associated with T2DM only in women with BMI ≥ 25 kg/m2 (HR 3.59, 95% CI 1.68-7.65) (p for interaction = 0.065). Although LS BMD T-score was similarly and negatively associated with incident VFs both in T2DM (OR 0.34, 95% CI 0.12-0.88) and non-DM women (OR 0.60, 95% CI 0.44-0.82) (p for interaction = 0.430), the FN BMD T-score was not found to be significantly associated with either non-VFs or VFs among T2DM women. Comparing T2DM and non-DM women with similar fracture risks, the mean difference in LS T-score was - 0.36 (95% CI - 1.77 to 1.04) for VF, and difference in FN T-score was 1.61 (95% CI - 0.11 to 3.34) for non-VF. In conclusion, Chinese postmenopausal women with T2DM had a similar risk of incident VFs, but a significantly higher risk of incident non-VF, compared to women without DM. Higher BMI did not modify the effect of T2DM on risk of VFs, but it increased the association between T2DM and risk of non-VFs. LS BMD T-score was similarly and negatively associated with VF risk in T2DM and non-DM women and appear to be useful for clinical evaluation of VF risk.

Calciotropic Hormones and the Prevalence of Vertebral Fractures in Chinese Postmenopausal Women with Vitamin D Insufficiency: Peking Vertebral Fracture Study.

This case-control study aimed to examine the effect of high serum parathyroid hormone (PTH) level, especially the effect of secondary hyperparathyroidism (SHPT) related to hypovitaminosis D, on bone metabolism and bone phenotypes. We included a total of 830 Chinese postmenopausal women aged ≥ 50 years with serum 25-hydroxyvitamin D (25(OH)D) level < 30 ng/ml, among whom 415 women had prevalent vertebral fractures (VFs) and others were age-matched controls. We measured serum levels of 25(OH)D, PTH and bone turnover markers (BTMs), which included C-terminal telopeptide of type I collagen (ß-CTX), N-aminoterminal prepeptide of type I procollagen (P1NP) and osteocalcin (OC). Bone mineral densities (BMDs) at lumbar spine and femoral neck were quantified by dual-energy X-ray absorptiometry. Morphometric VFs were validated by lateral radiograph of thoracolumbar spine. Compared to fracture-free controls, women with VFs exhibited a higher serum level of PTH and a higher percentage of SHPT (both p < 0.05), but had a similar serum level of 25(OH)D (p = 0.166). Positive correlations were depicted between PTH and BTMs (all p < 0.01), and between 25(OH)D and bone formation markers (p = 0.013 for OC, p = 0.068 for P1NP), whereas no significant correlation was identified between both calciotropic hormones and BMDs or between 25(OH)D and ß-CTX (all p > 0.05). Increasing PTH was associated with an increased risk of VFs independent of 25(OH)D and BMD [odds ratio (OR) per SD increase in PTH 1.016, 95% confidence interval (95% CI) 1.006-1.027]. Moreover, women with SHPT (i.e., > 68 pg/ml) had about three times odds for VF compared to women with normal PTH levels (OR 3.270, 95% CI 1.581-6.760). These data suggest that evaluated serum PTH level might promote the bone remodeling and then lead to increased risks of VFs among Chinese postmenopausal women with vitamin D insufficiency.

The potential role of circRNA_004229 in hair/epidermal regulation after MED1 ablation in keratinocytes.

Background/Aims: Mediator complex subunit 1 (MED1) is an important transcriptional co-activator involved in multiple signaling pathways. Previous studies indicated an essential role of MED1 in hair cycling and wound repair through regulating the transcription of mRNAs. Circular RNAs (circRNAs), as a novel class of non-coding RNAs, are involved in various skin biological functions. Our study aimed to investigate the circRNAs expression profile in MED1 epidermal conditional knockout mice (KO), and provide potential candidates as well as the mechanism underlying the circRNAs regulation in both hair follicles and epidermis. Method: Microarray based circRNA expression was determined in MED1 KO mice and wild type mice (WT). The expression level was further confirmed by qRT-PCR. We predicted a possible interaction network of circRNA/microRNA/mRNA by bioinformatics and constructed them with Cytoscape software. Expression of several candidate target mRNAs was verified using qRT-PCR. A TUNEL assay was performed to assess the apoptosis level of MED1 KO and WT skin. Results: Here we identified 109 (34-up, 75-down) distinct circRNAs through microarrays that are differently expressed in MED1 KO mice compared with WT mice (FC > 2 and p-value < 0.05), suggesting a potential role of circRNAs in epidermal regulation. Among these circRNAs, circRNA_004229 was found to decrease significantly after MED1 deletion. The most likely potential targets miRNA for circRNA_004229 include miR-149-5p and miR-207, which possibly further impede the expression of their target mRNA, Tnfrsf19 and Perp, respectively. Apoptosis was suppressed in MED1 KO mice, which implies a potential role of circRNAs in regulating epidermal biological processes including apoptosis. Conclusion: Our study determined the expression profile of circRNAs in MED1 KO skin, and provided hints that circRNA_004229 might be involved in the regulation of keratinocytes in both hair follicles and interfollicular epidermis through a ceRNA mechanism.

Phospholipase Cε deficiency delays the early stage of cutaneous wound healing and attenuates scar formation in mice.

This study aimed to investigate the role of phospholipase Cε (PLCε) in the skin wound healing process. PLCε, an effect factor of Ras/Rap small G protein, plays a crucial role in skin inflammation by regulating inflammatory cytokines. Inflammatory responses are closely associated with wound healing. Full-thickness skin wounds were made in the PLCε knockout (KO) and wild-type (WT) mice, and the healing process was analyzed. The macroscopic wound closure rate declined in the PLCε KO mice on days 3, 4, and 5 after wounding, following the decreased expression of interleukin (IL)-6, chemokine (C-X-C motif) ligand (Cxcl)-1, Cxcl-2, and chemokine (C-C motif) ligand (Ccl) 20. The proliferation rate of epidermal keratinocytes was not affected by PLCε, but silencing of PLCε resulted in the delayed migration of keratinocytes. Moreover, the scars were found to be much smaller in the PLCε KO mice than in the WT mice. The mRNA expression of Ccl20, collagen (Col) 6a1, and Col17a1 decreased in the PLCε KO mice. These results were in agreement with a previous hypothesis that PLCε might delay the early stage of cutaneous wound healing by inhibiting the migration of keratinocytes, and decrease the expression of Col6a1, Col17a1, and Ccl20 by inhibiting the inflammatory response to reduce scar formation. This study shed light on a novel role of PLCε in wound healing and provided new therapeutic approaches to target PLCε for diminishing scar formation after injury.

High prevalence of vitamin D deficiency in urban health checkup population.

BACKGROUND: Vitamin D deficiency is documented as a common health problem in the world. Limited data has been found on the prevalence of vitamin D deficiency in Beijing area. AIM: To investigate the prevalence s of vitamin D deficiency in urban Beijing residents and the seasonal and monthly serum 25(OH)D variation in this population. METHODS: This is an urban hospital based cross-sectional study lasting whole 2 years. 5531 (5-101 years old) urban Beijing residents for health checkup are recruited from December 9th, 2011 to December 8th, 2013. Each subject completed a questionnaire designed to quantify intake of vitamin D through food, vitamin D supplements, hours of sun exposure, sunscreen use over the past month. Serum 25(OH)D is statistically analyzed in accordance with gender, age, and time-lines. RESULTS: Vitamin D deficiency (Serum 25(OH)D level ≤20 ng/mL) and sever deficiency (Serum 25(OH)D level ≤ 10 ng/mL) are highly prevalent in this population. The prevalence of vitamin D deficiency is 87.1% and higher prevalence is found in female (89.0%) than male (84.9% P < 0.001). Severe vitamin D deficiency is also higher in female than male (59.3% and 42.7%, respectively, P < 0.001). Female under 20 and over 80 have lower 25(OH)D levels compared to 40-60 years old female (both P < 0.05). Severe vitamin D deficiency are also highly prevalence in this two group (60.9% and 54.1%) compared with 40-60 years old females (43.1%, both P < 0.05). Seasonal variation are also found in this population (P < 0.01). Autumn and summer have the higher 25(OH)D level than winter and spring in both genders (P < 0.001). Winter and spring have higher vitamin D deficiency and Severe deficiency than the other two seasons (P < 0.05). Serum 25(OH)D level peaks in October and troughed in April in both female and male. Lower serum 25(OH)D level are found in April than February (P < 0.05) in both gender. CONCLUSIONS: This is the first time to examine the prevalence of vitamin D deficiency among urban Beijing residents spanning the age spectrum. And Vitamin D deficiency and severe deficiency is found highly prevalent in this population, especially among females under 20 and older than 80 and in winter and spring seasons. Targeted prevention on vitamin D deficiency is urgent for this population.

MEN1 c.825­1G>A mutation in a family with multiple endocrine neoplasia type 1: A case report.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease characterized by combined occurrence of tumors and hyperplasia in tissues including the parathyroid, gastrointestinal endocrine tissue and anterior pituitary. Heterozygous germline mutation of the tumor suppressor gene MEN1 is the cause of the disease. Treatment and long­term follow up of patients with MEN1 are rarely reported in the literature due to the relative rarity of the disease; thus, there is limited understanding of tumor biology and behavior, and heterogeneous clinical presentation. This case report observed a family that presented with MEN1 c.825­1G>A mutation. The clinical features and treatment were followed up for >20 years. Detailed family history of this pedigree was investigated and followed up. Genomic DNA was extracted by standard methods from peripheral leukocytes. The coding sequence, including 9 coding exons and 16 splice junctions of the MEN1 gene of leukocyte DNA was determined. The proband presented with gastrinoma, pituitary tumors, hyperparathyroidism, thymoma and lung carcinoid tumors, and was followed from age 35 to 54 years old. During the 20 years, the patient underwent four surgeries: Trans­sphenoidal adenomectomy, followed by post operative radiotherapy at 39 years; hyperplasia parathyroid gland resection at 40 years; removal of pancreatic, head and neck, duodenal, gallbladder, bile duct, subtotal gastric (4/5) and pyloric region lymph nodes at age 41; and a thymectomy and left lung carcinoid tumor removal procedure at the age of 49. The patient died of unrelated trauma and had a relatively stable illness course. DNA sequence analysis revealed MEN1 gene c.825­1G>A or IVS 5­1G>A mutation in the family. Two carriers in the pedigree were identified and followed up. Data indicated that although MEN1 is a complex disease involving multiple organs and systems, MEN1 tumors should be considered surgically curable. If patients are properly cared for by multidisciplinary teams comprising of relevant specialists with experience in the diagnosis and treatment of patients with endocrine tumors, patients may have a relatively positive prognosis.

Association of genetic variants of vit D binding protein (DBP/GC) and of the enzyme catalyzing its 25-hydroxylation (DCYP2R1) and serum vit D in postmenopausal women.

OBJECTIVE: To determine if GC (group-specific component globulin) and CYP2R1 genetic variants have an association with serum 25-OHD3 levels, BMD or bone turnover markers in a population of Chinese postmenopausal women. DESIGN: We randomly selected 1494 postmenopausal women of the Han ethnic group from seven communities in Beijing. BMD was determined by dual energy X-ray absorptiometry; serum bone turnover markers and 25-OHD3 were measured by the automated Roche electrochemiluminescence system; genotypes of GC and CYP2R1 were detected by the TaqMan allelic discrimination assay. Multiple statistic methods were used to test the associations of SNP genotypes and vitamin D levels. RESULTS: In our sample, 89.6% women had vitamin D deficiency and another 9.8% had vitamin D insufficiency. The variants of rs2298849 (ß=0.105, P<0.001) in GC were significantly associated with serum 25-OHD3 levels. Allele G of rs2298849 might be protective for serum 25-OHD3 level. Among the haplotypes of rs222020-rs2298849, CG (ß=0.104, P=0.001) corresponded to increasing serum 25-OHD3 concentrations. CYP2R1 polymorphisms showed some significant association with serum ß-CTX and P1NP levels. CONCLUSIONS: We found that GC variants had a significant association with serum 25-OHD3 levels among postmenopausal women of the Han ethnic group in Beijing, while CYP2R1 variants were not found to be significant.

Association of GALNT3 gene polymorphisms with bone mineral density in Chinese postmenopausal women: the Peking Vertebral Fracture study.

OBJECTIVE: GALNT3 gene encodes the glycosyltransferase polypeptide N-acetylgalactosaminyltransferase-3 (ppGalNacT3), which initiates the O-glycosylation of fibroblast growth factor 23 (FGF23) that is important in phosphorous regulation. Inactivating mutations of the GALNT3 gene can cause familial tumoral calcinosis. The aim of present study is to investigate the association of GALNT3 polymorphisms with osteoporosis phenotypes in Chinese postmenopausal women. METHODS: A community-based population of 1,353 postmenopausal women was randomly selected in Beijing. Bone mineral densities (BMDs) of the lumbar spine, femoral neck (FN), and total hip (TH) were measured by dual-energy x-ray absorptiometry. Vertebral fracture phenotypes were ascertained by vertebral x-ray reading. Osteoporotic fracture phenotypes were obtained from questionnaires. Single nucleotide polymorphisms of GALNT3 were determined by TaqMan allelic discrimination assay. Differences in BMD, serum phosphorus, or serum calcium across diverse genotypes or haplotypes were analyzed by general linear model analysis of covariance. Linear regression or logistic regression was used for association analyses of different osteoporosis phenotypes, phosphorous, or calcium. Partial correlation was used to investigate the relationship between phosphorus or calcium and BMD. RESULTS: We found that polymorphisms of rs1863196, rs6710518, and rs13429321 were significantly associated with FN BMD (P values of 0.002, 0.003, and 0.002, respectively). Polymorphisms of rs1863196, rs6710518, rs4667492, rs13429321, and rs6721582 were associated with TH BMD (P values of 0.002, 0.004, 0.037, 0.005, and 0.014, respectively). Haplotype-1 additive and dominant models were found to be associated with TH BMD (P values of 0.035 and 0.024, respectively). Haplotype-2 dominant model was found to be associated with FN BMD (P = 0.003) and TH BMD (P = 0.001). CONCLUSIONS: GALNT3 may play a role in genetic susceptibility to osteoporosis among Chinese postmenopausal women. Efforts should be exerted to replicate our findings in other similar and ethnically diverse populations.

A haplotype of MATN3 is associated with vertebral fracture in Chinese postmenopausal women: Peking Vertebral Fracture (PK-VF) study.

The Matrilin3 gene (MATN3) encodes an extracellular matrix protein, which modulates chondrocyte differentiation. The aim of this study was to test for association of MATN3 polymorphisms with bone mineral density (BMD), fracture, vertebral fracture, bone turnover or 25-hydroxyvitamin D [25(OH)D] in postmenopausal women. A community-based population of 1488 postmenopausal women was randomly selected in Beijing. The history of fracture and vertebral fracture was obtained via questionnaire and vertebral X-ray respectively. BMD of lumbar spine (2-4), femoral neck and total hip were measured by dual energy X-ray absorptiometry. Serum N-terminal procollagen of type 1 collagen (P1NP), ß-isomerized type I collagen C-telopeptide breakdown products (ß-CTX) and 25(OH)D were quantified. Binary logistic regression revealed that Haplotype-4 was significantly associated with vertebral fracture risk in both additive model (p=0.023, OR=1.521) and dominant model (p=0.028, OR=1.623). The significance remained after 10,000 permutation tests to correct multiple testing (p=0.042). Re-selected age matched vertebral fracture case-control groups revealed similar associations in additive model (p=0.014, OR=1.927, 95%CI=1.142-3.253) and in dominant model (p=0.011, OR=2.231, 95%CI=1.200-4.148). However, no significant association was found between MATN3 polymorphisms and serum ß-CTX, P1NP, 25(OH)D levels, or BMD. In linear regression, Haplotype-2 approached marginal significance in association with femoral neck BMD T-score (p=0.050), but this would account for only 0.2% of BMD variation in our sample. This study suggests that Haplotype-4 of MATN3 is associated with vertebral fracture risk independent of BMD in Chinese postmenopausal women. Efforts should be made to replicate our finding in other, similar and ethnically diverse, populations.

The levels of bone turnover markers in Chinese postmenopausal women: Peking Vertebral Fracture study.

OBJECTIVE: The aim of this study was to evaluate serum N-aminoterminal propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (ß-CTX), and vitamin D status in healthy Chinese postmenopausal women. The study was also designed to investigate their possible relationships with osteoporosis phenotypes. METHODS: A community-based population of 1,724 postmenopausal women in Beijing was randomly selected. Serum bone turnover markers and 25-hydroxyvitamin D [25(OH)D] were tested by an automated Roche electrochemiluminescence system. Dual-energy x-ray absorptiometry was used to measure bone mineral density (BMD). RESULTS: The mean (SD) values of serum ß-CTX and P1NP were 0.439 (0.210) and 56.7 (27.9) ng/mL, respectively. The 25(OH)D level of postmenopausal women in Beijing was remarkably low (13.2 ± 5.4 ng/mL). Serum ß-CTX and P1NP levels were negatively correlated with BMDs of lumbar spine, femoral neck, and total hip (all P < 0.01). The cubic regression model better fitted the relationships of BMD and bone turnover markers. Serum ß-CTX levels were significantly higher in women with sustained osteoporotic fracture or vertebral fracture (P = 0.006 and 0.012, respectively). No association between P1NP and fracture or vertebral fracture was detected. The same situation applied to 25(OH)D. 25(OH)D was negatively correlated with ß-CTX and P1NP (r = -0.073 and -0.088, P = 0.002 and <0.001, respectively). CONCLUSIONS: Serum ß-CTX and P1NP levels were negatively correlated with BMD. ß-CTX was significantly higher in postmenopausal women with sustained fracture or vertebral fracture. Vitamin D deficiency was highly prevalent in postmenopausal women in Beijing.