Type 2 diabetes （T2D） is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis （OA）. Accordingl...Type 2 diabetes （T2D） is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis （OA）. Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic （n---70） and diabetes （n = 51） groups. Tibial plateaus were also collected from cadaver donors （n = 20） and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase （TRAP）, osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International （OARSI） scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~ osteoclasts and lower number of Osterix~ osteoprogenitors and Osteocalcin~ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.展开更多
With recent advances in biotechnology, genome-wide association study （GWAS） has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistica...With recent advances in biotechnology, genome-wide association study （GWAS） has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistical strategy is traditional logistical regression （LR） based on single-locus analysis. However, such a single-locus analysis leads to the well-known multiplicity problem, with a risk of inflating type I error and reducing power. Dimension reduction-based techniques, such as principal component-based logistic regression （PC-LR）, partial least squares-based logistic regression （PLS-LR）, have recently gained much attention in the analysis of high dimensional genomic data. However, the perfor- mance of these methods is still not clear, especially in GWAS. We conducted simulations and real data application to compare the type I error and power of PC-LR, PLS-LR and LR applicable to GWAS within a defined single nucleotide polymorphism （SNP） set region. We found that PC-LR and PLS can reasonably control type I error under null hypothesis. On contrast, LR, which is corrected by Bonferroni method, was more conserved in all simulation settings. In particular, we found that PC-LR and PLS-LR had comparable power and they both outperformed LR, especially when the causal SNP was in high linkage disequilibrium with genotyped ones and with a small effective size in simulation. Based on SNP set analysis, we applied all three methods to analyze non-small cell lung cancer GWAS data.展开更多
For the plane curves Γ,the maximal operator associated to it is defined by Mf(x)=sup|∫f(x-Γ(t))(r^(-1)t)r^(-1)dt| where is a Schwartz function.For a certain class of curves in R^2,M is shown to bounded on (H(R^2)...For the plane curves Γ,the maximal operator associated to it is defined by Mf(x)=sup|∫f(x-Γ(t))(r^(-1)t)r^(-1)dt| where is a Schwartz function.For a certain class of curves in R^2,M is shown to bounded on (H(R^2),Weak L^1(R^2).This extends the theorem of Stein & Wainger and the theo- rem of Weinberg.展开更多
Objective Modified upper abdominal cluster transplantation ( MCT) ,which was inspired by classical cluster transplant technique,has been proven more effective and feasible in the treatment of patients with end stage l...Objective Modified upper abdominal cluster transplantation ( MCT) ,which was inspired by classical cluster transplant technique,has been proven more effective and feasible in the treatment of patients with end stage liver diseases associated with insulin - dependent展开更多
The association of gluckinase (GCK) gene with type 2 (non-insulin-dependent) diabetes mellitus was investigated in 168 Chinese subjects (85 unrelated type 2 diabetics and 83 non-diabetic controls), The microsatellite ...The association of gluckinase (GCK) gene with type 2 (non-insulin-dependent) diabetes mellitus was investigated in 168 Chinese subjects (85 unrelated type 2 diabetics and 83 non-diabetic controls), The microsatellite polymorphism marker, GCK-5', was amplified with polymerase chain reaction. Four alleles were observed in Chinese population with length varying from 137bp to 143bp and the most common one being the 139bp allele 3. In comparison with non-diabetics, allele 4 was significantly increased in type 2 diabetes (10% versus 38, respectively; X(2)=6.773, P=0.009); genotype 44 and 4X (X denotes any allele other than allele 4) were significantly increased in type 2 diabetes (16% versus 6% respectively; X(2)=6.439, P=0.011), The frequency difference was also shown in overweight / obese subgroup comparison (X(2)=7.718, P=0.021), but not in lean / normal-weight subgroup comparison, No differences of age of onset and frequency of positive family history were observed between type 2 diabetic patients with genotype 44 or 4X and those with XX. The risk for type 2 diabetes in Chinese with genotype 44 or 4X was about 3.5 times higher than in Chinese with genotype XX. Therefore, GCK gene was associated with Chinese type 2 diabetes.展开更多
Objective To explore the influence of a polymorphism of protein tyrosine phosphatase receptor type R(PTPRR)gene rs1513105 on abnormal brain activities in resting-state patients with major depressive disorder(MDD)using...Objective To explore the influence of a polymorphism of protein tyrosine phosphatase receptor type R(PTPRR)gene rs1513105 on abnormal brain activities in resting-state patients with major depressive disorder(MDD)using the gene-imaging technology.Methods 54MDD and 43 gender-,age-,and education-matched con-展开更多
Single-cell RNA sequencing(scRNA-seq)is revolutionizing the study of complex and dynamic cellular mechanisms.However,cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual ...Single-cell RNA sequencing(scRNA-seq)is revolutionizing the study of complex and dynamic cellular mechanisms.However,cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual curation,which is cumbersome and subjective.The increasing number of scRNA-seq datasets,as well as numerous published genetic studies,has motivated us to build a comprehensive human cell type reference atlas.Here,we present decoding Cell type Specificity(deCS),an automatic cell type annotation method augmented by a comprehensive collection of human cell type expression profiles and marker genes.We used deCS to annotate scRNAseq data from various tissue types and systematically evaluated the annotation accuracy under different conditions,including reference panels,sequencing depth,and feature selection strategies.Our results demonstrate that expanding the references is critical for improving annotation accuracy.Compared to many existing state-of-the-art annotation tools,deCS significantly reduced computation time and increased accuracy.deCS can be integrated into the standard scRNA-seq analytical pipeline to enhance cell type annotation.Finally,we demonstrated the broad utility of deCS to identify trait-cell type associations in 51 human complex traits,providing deep insights into the cellular mechanisms underlying disease pathogenesis.展开更多
基金supported by National Natural Science Foundation of China(NSFC Nos.81601930 and U1613224)Natural Science Foundation of Guangxi(2016JJB140050)+1 种基金Research Grant Council of Hong Kong(HKU715213 and 17206916)Shenzhen Peacock Project
文摘Type 2 diabetes （T2D） is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis （OA）. Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic （n---70） and diabetes （n = 51） groups. Tibial plateaus were also collected from cadaver donors （n = 20） and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase （TRAP）, osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International （OARSI） scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~ osteoclasts and lower number of Osterix~ osteoprogenitors and Osteocalcin~ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.
基金founded by the National Natural Science Foundation of China(81202283,81473070,81373102 and81202267)Key Grant of Natural Science Foundation of the Jiangsu Higher Education Institutions of China(10KJA330034 and11KJA330001)+1 种基金the Research Fund for the Doctoral Program of Higher Education of China(20113234110002)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine)
文摘With recent advances in biotechnology, genome-wide association study （GWAS） has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistical strategy is traditional logistical regression （LR） based on single-locus analysis. However, such a single-locus analysis leads to the well-known multiplicity problem, with a risk of inflating type I error and reducing power. Dimension reduction-based techniques, such as principal component-based logistic regression （PC-LR）, partial least squares-based logistic regression （PLS-LR）, have recently gained much attention in the analysis of high dimensional genomic data. However, the perfor- mance of these methods is still not clear, especially in GWAS. We conducted simulations and real data application to compare the type I error and power of PC-LR, PLS-LR and LR applicable to GWAS within a defined single nucleotide polymorphism （SNP） set region. We found that PC-LR and PLS can reasonably control type I error under null hypothesis. On contrast, LR, which is corrected by Bonferroni method, was more conserved in all simulation settings. In particular, we found that PC-LR and PLS-LR had comparable power and they both outperformed LR, especially when the causal SNP was in high linkage disequilibrium with genotyped ones and with a small effective size in simulation. Based on SNP set analysis, we applied all three methods to analyze non-small cell lung cancer GWAS data.
文摘For the plane curves Γ,the maximal operator associated to it is defined by Mf(x)=sup|∫f(x-Γ(t))(r^(-1)t)r^(-1)dt| where is a Schwartz function.For a certain class of curves in R^2,M is shown to bounded on (H(R^2),Weak L^1(R^2).This extends the theorem of Stein & Wainger and the theo- rem of Weinberg.
文摘Objective Modified upper abdominal cluster transplantation ( MCT) ,which was inspired by classical cluster transplant technique,has been proven more effective and feasible in the treatment of patients with end stage liver diseases associated with insulin - dependent
文摘The association of gluckinase (GCK) gene with type 2 (non-insulin-dependent) diabetes mellitus was investigated in 168 Chinese subjects (85 unrelated type 2 diabetics and 83 non-diabetic controls), The microsatellite polymorphism marker, GCK-5', was amplified with polymerase chain reaction. Four alleles were observed in Chinese population with length varying from 137bp to 143bp and the most common one being the 139bp allele 3. In comparison with non-diabetics, allele 4 was significantly increased in type 2 diabetes (10% versus 38, respectively; X(2)=6.773, P=0.009); genotype 44 and 4X (X denotes any allele other than allele 4) were significantly increased in type 2 diabetes (16% versus 6% respectively; X(2)=6.439, P=0.011), The frequency difference was also shown in overweight / obese subgroup comparison (X(2)=7.718, P=0.021), but not in lean / normal-weight subgroup comparison, No differences of age of onset and frequency of positive family history were observed between type 2 diabetic patients with genotype 44 or 4X and those with XX. The risk for type 2 diabetes in Chinese with genotype 44 or 4X was about 3.5 times higher than in Chinese with genotype XX. Therefore, GCK gene was associated with Chinese type 2 diabetes.
文摘Objective To explore the influence of a polymorphism of protein tyrosine phosphatase receptor type R(PTPRR)gene rs1513105 on abnormal brain activities in resting-state patients with major depressive disorder(MDD)using the gene-imaging technology.Methods 54MDD and 43 gender-,age-,and education-matched con-
基金supported by National Institutes of Health grants(Grant Nos.R01LM012806R,I01DE030122,and R01DE029818)support from Cancer Prevention and Research Institute of Texas(Grant Nos.CPRIT RP180734 and RP210045),United States.
文摘Single-cell RNA sequencing(scRNA-seq)is revolutionizing the study of complex and dynamic cellular mechanisms.However,cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual curation,which is cumbersome and subjective.The increasing number of scRNA-seq datasets,as well as numerous published genetic studies,has motivated us to build a comprehensive human cell type reference atlas.Here,we present decoding Cell type Specificity(deCS),an automatic cell type annotation method augmented by a comprehensive collection of human cell type expression profiles and marker genes.We used deCS to annotate scRNAseq data from various tissue types and systematically evaluated the annotation accuracy under different conditions,including reference panels,sequencing depth,and feature selection strategies.Our results demonstrate that expanding the references is critical for improving annotation accuracy.Compared to many existing state-of-the-art annotation tools,deCS significantly reduced computation time and increased accuracy.deCS can be integrated into the standard scRNA-seq analytical pipeline to enhance cell type annotation.Finally,we demonstrated the broad utility of deCS to identify trait-cell type associations in 51 human complex traits,providing deep insights into the cellular mechanisms underlying disease pathogenesis.
