المؤلفون: Xiaohui Tao, Li Liu, Xingguang Yang, Zhe Wei, Zhongzhong Chen, Ge Zhang, Zhenlin Zhang, Hua Yue

مصطلحات موضوعية: Endocrinology, Reproduction, Cell Metabolism, Paget’s disease of bone, clinical characteristics, SQSTM1, whole-exome sequencing (WES), disease-causing gene

الوصف: Objective To evaluate the clinical features of sporadic Paget’s disease of bone (PDB) in China and further explore the underlying genetic abnormalities of the disease. Methods Clinical characteristics, biochemical indices, bone turnover markers and radiographic examinations of the patients were collected. Genomic DNA was extracted from peripheral blood and whole-exome sequencing was carried out to identify the potential pathogenic genes. The pathogenicity of the variants was thereafter investigated by bioinformatics analysis. Results A total of 50 patients (57.20 ± 15.52 years, male/female: 1.63: 1) with PDB were included and the mean onset age was 48.34 years (48.34 ± 17.24 years). 94.0% of the patients exhibited symptomatic patterns described as bone pain (86.0%), elevated skin temperature at the lesion site (26.0%), bone deformity (22.0%) and local swelling (18.0%). The most frequently involved lesion sites were pelvis (52.0%), femur (42.0%), tibia (28.0%), skull (28.0%) and spine (18.0%), respectively. Additionally, 40.0% of them accompanied with osteoarthritis, 14.0% with pathological fractures, and the misdiagnosis rate of PDB was as high as 36.0%. Serum level of alkaline phosphatase was significantly increased, with the mean value of 284.00 U/L (quartiles, 177.00-595.00 U/L). Two heterozygous missense mutations of SQSTM1 gene (c.1211T>C, M404T) and one novel heterozygous missense mutation in HNRNPA2B1 gene (c.989C>T, p. P330L) were identified in our study. Moreover, several potential disease-causing genes were detected and markedly enriched in the pathways of neurodegeneration (including WNT16, RYR3 and RYR1 genes) and amyotrophic lateral sclerosis (ALS, including NUP205, CAPN2, and NUP214 genes). Conclusion In contrast to Western patients, Chinese patients have an earlier onset age, more severe symptoms, and lower frequency of SQSTM1 gene mutation (4.0%). Moreover, a novel heterozygous missense mutation in HNRNPA2B1 gene was identified in one male patient with isolated bone phenotype. As for other ...

العلاقة: https://figshare.com/articles/figure/Image_1_Clinical_Characteristics_and_Pathogenic_Gene_Identification_in_Chinese_Patients_With_Paget_s_Disease_of_Bone_jpeg/19329038Test

الإتاحة: https://doi.org/10.3389/fendo.2022.850462.s001Test
https://figshare.com/articles/figure/Image_1_Clinical_Characteristics_and_Pathogenic_Gene_Identification_in_Chinese_Patients_With_Paget_s_Disease_of_Bone_jpeg/19329038Test

المؤلفون: Xiaohui Tao, Li Liu, Xingguang Yang, Zhe Wei, Zhongzhong Chen, Ge Zhang, Zhenlin Zhang, Hua Yue

مصطلحات موضوعية: Endocrinology, Reproduction, Cell Metabolism, Paget’s disease of bone, clinical characteristics, SQSTM1, whole-exome sequencing (WES), disease-causing gene

الوصف: Objective To evaluate the clinical features of sporadic Paget’s disease of bone (PDB) in China and further explore the underlying genetic abnormalities of the disease. Methods Clinical characteristics, biochemical indices, bone turnover markers and radiographic examinations of the patients were collected. Genomic DNA was extracted from peripheral blood and whole-exome sequencing was carried out to identify the potential pathogenic genes. The pathogenicity of the variants was thereafter investigated by bioinformatics analysis. Results A total of 50 patients (57.20 ± 15.52 years, male/female: 1.63: 1) with PDB were included and the mean onset age was 48.34 years (48.34 ± 17.24 years). 94.0% of the patients exhibited symptomatic patterns described as bone pain (86.0%), elevated skin temperature at the lesion site (26.0%), bone deformity (22.0%) and local swelling (18.0%). The most frequently involved lesion sites were pelvis (52.0%), femur (42.0%), tibia (28.0%), skull (28.0%) and spine (18.0%), respectively. Additionally, 40.0% of them accompanied with osteoarthritis, 14.0% with pathological fractures, and the misdiagnosis rate of PDB was as high as 36.0%. Serum level of alkaline phosphatase was significantly increased, with the mean value of 284.00 U/L (quartiles, 177.00-595.00 U/L). Two heterozygous missense mutations of SQSTM1 gene (c.1211T>C, M404T) and one novel heterozygous missense mutation in HNRNPA2B1 gene (c.989C>T, p. P330L) were identified in our study. Moreover, several potential disease-causing genes were detected and markedly enriched in the pathways of neurodegeneration (including WNT16, RYR3 and RYR1 genes) and amyotrophic lateral sclerosis (ALS, including NUP205, CAPN2, and NUP214 genes). Conclusion In contrast to Western patients, Chinese patients have an earlier onset age, more severe symptoms, and lower frequency of SQSTM1 gene mutation (4.0%). Moreover, a novel heterozygous missense mutation in HNRNPA2B1 gene was identified in one male patient with isolated bone phenotype. As for other ...

العلاقة: https://figshare.com/articles/figure/Image_2_Clinical_Characteristics_and_Pathogenic_Gene_Identification_in_Chinese_Patients_With_Paget_s_Disease_of_Bone_jpeg/19329041Test

الإتاحة: https://doi.org/10.3389/fendo.2022.850462.s002Test
https://figshare.com/articles/figure/Image_2_Clinical_Characteristics_and_Pathogenic_Gene_Identification_in_Chinese_Patients_With_Paget_s_Disease_of_Bone_jpeg/19329041Test

المؤلفون: Yang Xu, Li Shen, Lianyong Liu, Zhenlin Zhang, Weiwei Hu

مصطلحات موضوعية: Endocrinology, Reproduction, Cell Metabolism, undercarboxylated osteocalcin, bone mineral density, bone turnover markers, osteopenia, osteoporosis

الوصف: Objective Undercarboxylated osteocalcin (ucOC) is one form of osteocalcin lacking full carboxylation, which plays an important role in bone homeostasis, glucose homeostasis, and energy metabolism. Our aim is to obtain the profile of serum ucOC level according to gender and age and explore its associations with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteopenia and osteoporosis in the Chinese population. Methods This is a cross-sectional study with 900 subjects, composed of 431 men and 469 women. Clinical information was collected, and BMD values of the lumbar spine (L1–4), left femoral neck, and total hip were scanned. Biochemical markers including hepatic and renal function, serum calcium, serum phosphorus, procollagen type 1 N-propeptide (P1NP) β-CrossLaps of type I collagen-containing cross-linked C-telopeptide (β-CTX) intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and ucOC were measured. Results We found that the median ucOC level was higher in men than women [men, 2.6 ng/ml; women, 1.6 ng/ml; p < 0.001]. The profile according to age showed that ucOC levels were the lowest at the age of 40–49 years in both men [2.55 ng/ml (95% CI = 1.96–3.13 ng/ml)] and women [1.57 ng/ml (95% CI = 1.12–2.03 ng/ml)]; in patients younger than 49 years, they decreased with age; then over 50 years, they quickly increased. Furthermore, we found that a higher ucOC level was correlated with lower BMD values at the lumbar spine (men, r = −0.128, p = 0.013; women, r = −0.321, p < 0.001), femoral neck (men, r = −0.095, p = 0.062; women, r = −0.260, p < 0.001), and total hip (men, r = −0.123, p = 0.015; women, r = −0.209, p < 0.001) and higher P1NP (men, r = 0.307, p < 0.001; women, r = 0.239, p < 0.001) and β-CTX (men, r = 0.169, p = 0.001; women, r = 0.354, p < 0.001) levels in both men and women. Furthermore, we also showed that a 1 − SD increase in ucOC was associated with an odds ratio (OR) of 1.63 and 1.70 for having osteopenia or osteoporosis in men and ...

العلاقة: https://figshare.com/articles/figure/Image_1_Undercarboxylated_Osteocalcin_and_Its_Associations_With_Bone_Mineral_Density_Bone_Turnover_Markers_and_Prevalence_of_Osteopenia_and_Osteoporosis_in_Chinese_Population_A_Cross-Sectional_Study_jpeg/20280117Test

الإتاحة: https://doi.org/10.3389/fendo.2022.843912.s001Test
https://figshare.com/articles/figure/Image_1_Undercarboxylated_Osteocalcin_and_Its_Associations_With_Bone_Mineral_Density_Bone_Turnover_Markers_and_Prevalence_of_Osteopenia_and_Osteoporosis_in_Chinese_Population_A_Cross-Sectional_Study_jpeg/20280117Test

المؤلفون: Zhongjian Xie, Weibo Xia, Zhenlin Zhang, Wen Wu, Chunyan Lu, Shuqing Tao, Lijun Wu, Jiemei Gu, Julie Chandler, Senaka Peter, Hang Yuan, Ting Wu, Eryuan Liao

مصطلحات موضوعية: Endocrinology, Reproduction, Cell Metabolism, vitamin D deficiency, postmenopausal women, winter, urban, intact parathyroid hormone

الوصف: Purpose: We aimed to investigate the status of serum 25-hydroxyvitamin D [25(OH)D] among Chinese postmenopausal women in a multicenter cross-sectional study. Methods: Non-institutionalized postmenopausal women aged ≥55 years were recruited from urban and rural areas in 7 geographically different regions in China. Subject enrollment was executed during the summer and the winter. Vitamin D insufficiency and deficiency were defined as 25(OH)D < 30 and< 20 ng/ml, and was measured by liquid chromatography-tandem mass spectrometry. Women were referred to a dual-energy x-ray absorptiometry (DXA) if they had a medium-to-high fracture risk suggested by Osteoporosis Self-Assessment Tool for Asians (OSTA). Results: Among all subjects, 91.2% (1,535/1,684, 95%CI: 89.7, 92.5) had vitamin D insufficiency and 61.3% had vitamin D deficiency (1,033/1,684, 95%CI: 59.0, 63.7). The prevalence of vitamin D deficiency was significantly higher in urban dwellers (64.9 vs. 57.7% in rural, P = 0.002) and in winter-enrolled subjects (84.7 vs. 41.3% in summer, P < 0.0001). The prevalence of vitamin D inadequacy did not increase in trend by latitude and was numerically lower in women who had high fracture risk and osteoporosis. A non-curvilinear change of intact parathyroid hormone (iPTH) levels was observed at 25(OH)D >16.78 ng/mL. Conclusions: The prevalence of vitamin D inadequacy was remarkable among Chinese postmenopausal women and independent of fracture risk assessed by OSTA or osteoporosis suggested by DXA. Winter season, urban residence, however not latitude, were significantly associated with a higher likelihood of vitamin D deficiency. Optimal vitamin D status for iPTH and bone-related outcomes merits further investigation in this population.

العلاقة: https://figshare.com/articles/figure/Image_2_Prevalence_of_Vitamin_D_Inadequacy_Among_Chinese_Postmenopausal_Women_A_Nationwide_Multicenter_Cross-Sectional_Study_TIF/7553333Test

الإتاحة: https://doi.org/10.3389/fendo.2018.00782.s002Test
https://figshare.com/articles/figure/Image_2_Prevalence_of_Vitamin_D_Inadequacy_Among_Chinese_Postmenopausal_Women_A_Nationwide_Multicenter_Cross-Sectional_Study_TIF/7553333Test

المؤلفون: Zhongjian Xie, Weibo Xia, Zhenlin Zhang, Wen Wu, Chunyan Lu, Shuqing Tao, Lijun Wu, Jiemei Gu, Julie Chandler, Senaka Peter, Hang Yuan, Ting Wu, Eryuan Liao

مصطلحات موضوعية: Endocrinology, Reproduction, Cell Metabolism, vitamin D deficiency, postmenopausal women, winter, urban, intact parathyroid hormone

الوصف: Purpose: We aimed to investigate the status of serum 25-hydroxyvitamin D [25(OH)D] among Chinese postmenopausal women in a multicenter cross-sectional study. Methods: Non-institutionalized postmenopausal women aged ≥55 years were recruited from urban and rural areas in 7 geographically different regions in China. Subject enrollment was executed during the summer and the winter. Vitamin D insufficiency and deficiency were defined as 25(OH)D < 30 and< 20 ng/ml, and was measured by liquid chromatography-tandem mass spectrometry. Women were referred to a dual-energy x-ray absorptiometry (DXA) if they had a medium-to-high fracture risk suggested by Osteoporosis Self-Assessment Tool for Asians (OSTA). Results: Among all subjects, 91.2% (1,535/1,684, 95%CI: 89.7, 92.5) had vitamin D insufficiency and 61.3% had vitamin D deficiency (1,033/1,684, 95%CI: 59.0, 63.7). The prevalence of vitamin D deficiency was significantly higher in urban dwellers (64.9 vs. 57.7% in rural, P = 0.002) and in winter-enrolled subjects (84.7 vs. 41.3% in summer, P < 0.0001). The prevalence of vitamin D inadequacy did not increase in trend by latitude and was numerically lower in women who had high fracture risk and osteoporosis. A non-curvilinear change of intact parathyroid hormone (iPTH) levels was observed at 25(OH)D >16.78 ng/mL. Conclusions: The prevalence of vitamin D inadequacy was remarkable among Chinese postmenopausal women and independent of fracture risk assessed by OSTA or osteoporosis suggested by DXA. Winter season, urban residence, however not latitude, were significantly associated with a higher likelihood of vitamin D deficiency. Optimal vitamin D status for iPTH and bone-related outcomes merits further investigation in this population.

العلاقة: https://figshare.com/articles/figure/Image_3_Prevalence_of_Vitamin_D_Inadequacy_Among_Chinese_Postmenopausal_Women_A_Nationwide_Multicenter_Cross-Sectional_Study_TIF/7553336Test

الإتاحة: https://doi.org/10.3389/fendo.2018.00782.s003Test
https://figshare.com/articles/figure/Image_3_Prevalence_of_Vitamin_D_Inadequacy_Among_Chinese_Postmenopausal_Women_A_Nationwide_Multicenter_Cross-Sectional_Study_TIF/7553336Test

المؤلفون: Zhongjian Xie, Weibo Xia, Zhenlin Zhang, Wen Wu, Chunyan Lu, Shuqing Tao, Lijun Wu, Jiemei Gu, Julie Chandler, Senaka Peter, Hang Yuan, Ting Wu, Eryuan Liao

مصطلحات موضوعية: Endocrinology, Reproduction, Cell Metabolism, vitamin D deficiency, postmenopausal women, winter, urban, intact parathyroid hormone

الوصف: Purpose: We aimed to investigate the status of serum 25-hydroxyvitamin D [25(OH)D] among Chinese postmenopausal women in a multicenter cross-sectional study. Methods: Non-institutionalized postmenopausal women aged ≥55 years were recruited from urban and rural areas in 7 geographically different regions in China. Subject enrollment was executed during the summer and the winter. Vitamin D insufficiency and deficiency were defined as 25(OH)D < 30 and< 20 ng/ml, and was measured by liquid chromatography-tandem mass spectrometry. Women were referred to a dual-energy x-ray absorptiometry (DXA) if they had a medium-to-high fracture risk suggested by Osteoporosis Self-Assessment Tool for Asians (OSTA). Results: Among all subjects, 91.2% (1,535/1,684, 95%CI: 89.7, 92.5) had vitamin D insufficiency and 61.3% had vitamin D deficiency (1,033/1,684, 95%CI: 59.0, 63.7). The prevalence of vitamin D deficiency was significantly higher in urban dwellers (64.9 vs. 57.7% in rural, P = 0.002) and in winter-enrolled subjects (84.7 vs. 41.3% in summer, P < 0.0001). The prevalence of vitamin D inadequacy did not increase in trend by latitude and was numerically lower in women who had high fracture risk and osteoporosis. A non-curvilinear change of intact parathyroid hormone (iPTH) levels was observed at 25(OH)D >16.78 ng/mL. Conclusions: The prevalence of vitamin D inadequacy was remarkable among Chinese postmenopausal women and independent of fracture risk assessed by OSTA or osteoporosis suggested by DXA. Winter season, urban residence, however not latitude, were significantly associated with a higher likelihood of vitamin D deficiency. Optimal vitamin D status for iPTH and bone-related outcomes merits further investigation in this population.

العلاقة: https://figshare.com/articles/figure/Image_1_Prevalence_of_Vitamin_D_Inadequacy_Among_Chinese_Postmenopausal_Women_A_Nationwide_Multicenter_Cross-Sectional_Study_TIF/7553330Test

الإتاحة: https://doi.org/10.3389/fendo.2018.00782.s001Test
https://figshare.com/articles/figure/Image_1_Prevalence_of_Vitamin_D_Inadequacy_Among_Chinese_Postmenopausal_Women_A_Nationwide_Multicenter_Cross-Sectional_Study_TIF/7553330Test

المؤلفون: Yang Xu, Li Shen, Lianyong Liu, Zhenlin Zhang, Weiwei Hu

مصطلحات موضوعية: Endocrinology, Reproduction, Cell Metabolism, undercarboxylated osteocalcin, bone mineral density, bone turnover markers, osteopenia, osteoporosis, socio, envir

الوصف: Objective Undercarboxylated osteocalcin (ucOC) is one form of osteocalcin lacking full carboxylation, which plays an important role in bone homeostasis, glucose homeostasis, and energy metabolism. Our aim is to obtain the profile of serum ucOC level according to gender and age and explore its associations with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteopenia and osteoporosis in the Chinese population. Methods This is a cross-sectional study with 900 subjects, composed of 431 men and 469 women. Clinical information was collected, and BMD values of the lumbar spine (L1–4), left femoral neck, and total hip were scanned. Biochemical markers including hepatic and renal function, serum calcium, serum phosphorus, procollagen type 1 N-propeptide (P1NP) β-CrossLaps of type I collagen-containing cross-linked C-telopeptide (β-CTX) intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and ucOC were measured. Results We found that the median ucOC level was higher in men than women [men, 2.6 ng/ml; women, 1.6 ng/ml; p < 0.001]. The profile according to age showed that ucOC levels were the lowest at the age of 40–49 years in both men [2.55 ng/ml (95% CI = 1.96–3.13 ng/ml)] and women [1.57 ng/ml (95% CI = 1.12–2.03 ng/ml)]; in patients younger than 49 years, they decreased with age; then over 50 years, they quickly increased. Furthermore, we found that a higher ucOC level was correlated with lower BMD values at the lumbar spine (men, r = −0.128, p = 0.013; women, r = −0.321, p < 0.001), femoral neck (men, r = −0.095, p = 0.062; women, r = −0.260, p < 0.001), and total hip (men, r = −0.123, p = 0.015; women, r = −0.209, p < 0.001) and higher P1NP (men, r = 0.307, p < 0.001; women, r = 0.239, p < 0.001) and β-CTX (men, r = 0.169, p = 0.001; women, r = 0.354, p < 0.001) levels in both men and women. Furthermore, we also showed that a 1 − SD increase in ucOC was associated with an odds ratio (OR) of 1.63 and 1.70 for having osteopenia or osteoporosis in men and .

العلاقة: https://doi.org/10.3389/fendo.2022.843912.s001Test

الإتاحة: https://doi.org/10.3389/fendo.2022.843912.s001Test

المؤلفون: Damao Huang (410413), Yuejin Li (410414), Na Liu (102929), Zhenlin Zhang (105991), Zhengke Peng (410412), Chaojun Duan (326228), Xiaowei Tang (410415), Gongjun Tan (549370), Guangrong Yan (2007337), Faqing Tang (326220)

مصطلحات موضوعية: Biophysics, Biochemistry, Microbiology, Cell Biology, Genetics, Molecular Biology, Physiology, Immunology, Cancer, Infectious Diseases, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Dinitrosopiperazine, Nasopharyngeal carcinoma, Metastasis, Quantitative phosphoproteomics

الوصف: Authors’ original file for figure 7

العلاقة: https://figshare.com/articles/figure/Additional_file_10_of_Identification_of_novel_signaling_components_in_N_N_-Dinitrosopiperazine-mediated_metastasis_of_nasopharyngeal_Carcinoma_by_quantitative_phosphoproteomics/19090814Test

الإتاحة: https://doi.org/10.6084/m9.figshare.19090814.v1Test

المؤلفون: Damao Huang (410413), Yuejin Li (410414), Na Liu (102929), Zhenlin Zhang (105991), Zhengke Peng (410412), Chaojun Duan (326228), Xiaowei Tang (410415), Gongjun Tan (549370), Guangrong Yan (2007337), Faqing Tang (326220)

مصطلحات موضوعية: Biophysics, Biochemistry, Microbiology, Cell Biology, Genetics, Molecular Biology, Physiology, Immunology, Cancer, Infectious Diseases, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Dinitrosopiperazine, Nasopharyngeal carcinoma, Metastasis, Quantitative phosphoproteomics

الوصف: Authors’ original file for figure 8

العلاقة: https://figshare.com/articles/figure/Additional_file_11_of_Identification_of_novel_signaling_components_in_N_N_-Dinitrosopiperazine-mediated_metastasis_of_nasopharyngeal_Carcinoma_by_quantitative_phosphoproteomics/19090817Test

الإتاحة: https://doi.org/10.6084/m9.figshare.19090817.v1Test

المؤلفون: Damao Huang (410413), Yuejin Li (410414), Na Liu (102929), Zhenlin Zhang (105991), Zhengke Peng (410412), Chaojun Duan (326228), Xiaowei Tang (410415), Gongjun Tan (549370), Guangrong Yan (2007337), Faqing Tang (326220)

مصطلحات موضوعية: Biophysics, Biochemistry, Microbiology, Cell Biology, Genetics, Molecular Biology, Physiology, Immunology, Cancer, Infectious Diseases, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Dinitrosopiperazine, Nasopharyngeal carcinoma, Metastasis, Quantitative phosphoproteomics

الوصف: Authors’ original file for figure 1

العلاقة: https://figshare.com/articles/figure/Additional_file_4_of_Identification_of_novel_signaling_components_in_N_N_-Dinitrosopiperazine-mediated_metastasis_of_nasopharyngeal_Carcinoma_by_quantitative_phosphoproteomics/19090829Test

الإتاحة: https://doi.org/10.6084/m9.figshare.19090829.v1Test