AIM: To evaluate the efficacy and toxicity of stereotactic body radiotherapy using Cyber Knife for locally advanced unresectable and metastatic pancreatic cancer.METHODS: From June 2010 to May 2014,25 patients with lo...AIM: To evaluate the efficacy and toxicity of stereotactic body radiotherapy using Cyber Knife for locally advanced unresectable and metastatic pancreatic cancer.METHODS: From June 2010 to May 2014,25 patients with locally advanced unresectable and metastatic pancreatic cancer underwent stereotactic body radiotherapy.Nine patients presented with unresectable locally advanced disease and 16 had metastatic disease.Primary end-points of this study were overall survival,relief of abdominal pain,and toxicity.RESULTS: Fourteen patients were treated with a total dose of 30-36 Gy in three fractions and the remainder with 40-48 Gy in four fractions.Median follow-up was 11 mo(range: 2-25 mo).The median survival duration calculated from the time of stereotactic body radiotherapy for the entire group,the locally advanced group,and the metastatic group was 9.0 mo,13.5 mo,and 8.5 mo,respectively.Overall survival was 37% and 18% at one and two years,respectively.Abdominal pain relief was achieved within 2 wk of completing radiotherapy in the patients who received successful palliation(13 of 20 patients had significant pain).Five patients(20%) had grade 1 nausea,and one(4%) had grade 2 nausea.No acute grade 3+ toxicity was seen.CONCLUSION: Stereotactic body radiotherapy using the Cyber Knife system is a promising,noninvasive,palliative treatment with acceptable toxicity for locally advanced unresectable and metastatic pancreatic cancer.展开更多
BACKGROUND:Early reperfusion can effectively treat acute myocardial infarction(AMI) and reduce the mortality signif icantly. This study aimed to compare the role of plasma microRNA-1(miR-1) and cardiac troponin T(cTnT...BACKGROUND:Early reperfusion can effectively treat acute myocardial infarction(AMI) and reduce the mortality signif icantly. This study aimed to compare the role of plasma microRNA-1(miR-1) and cardiac troponin T(cTnT) in early diagnosis of AMI patients.METHODS:From May 2011 to May 2012,plasma samples were collected from 56 AMI patients and 28 non-AMI controls. The expression of plasma miR-1 was measured by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),and the level of plasma cTnT was measured using electrochemiluminescence-based methods on an Elecsys 2010 Immunoassay Analyzer. SPSS 16.0 was used for the statistical analysis of the results. Data were expressed as mean±standard deviation unless otherwise described. The differences about clinical characteristics between the AMI patients and controls were tested using Student's t test or Fisher's exact test. The Mann-Whitney U test was conducted to compare the expression of microRNAs between the AMI patients and controls. MicroRNAs expression between different intervals of the AMI patients was compared using Wilcoxon's signed-rank test. The receiver operating characteristic(ROC) curve was established to discriminate the AMI patients from the controls.RESULTS:In the present study,the expression of plasma miR-1 was signifi cantly increased in the AMI patients compared with the healthy controls(P<0.01). The plasma miR-1 in the AMI patients decreased to the normal level at 14 days(P>0.05). The expression of plasma miR-1 was not related to the clinical characteristics of the study population(P>0.05). ROC curve analyses demonstrated that miR-1 was specifi c and sensitive for the early diagnosis of AMI,but not superior to cTnT.CONCLUSION:Plasma miR-1 could be used in the early diagnosis of AMI,but it is similar to cTnT.展开更多
Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin (OCN) in predicting diabetes was reported, but with conflicting results. No study has explored...Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin (OCN) in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen (CTX) and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant (NGT) women at baseline were invited for follow-up. The incidence of diabetes and prediabetes (collectively defined as dysglycemia) was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% (95% confidence interval (CI), 6.8%-30.70/0)] compared with the lower [31.0% (95% CI, 17.2%-46.1%)] and upper [46.5% (95% CI, 31.2%-62.6%)] tertiles of CTX, with a significant difference seen between the middle and upper tertiles (P = 0.002 5). After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 (95% CI, 1.73-28.99) when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.展开更多
In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism (PHPT) changed from a symptomatic to an ...In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism (PHPT) changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT con- tinues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.展开更多
Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair u...Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.展开更多
Objective:To investigate the effect of lipoxin receptor agonist BML-111 on the NLRP3 inflammasome after traumatic brain injury in rats.Methods:Sixty male Sprague-Dawley rats,weighing 280~340 g,were randomly divided in...Objective:To investigate the effect of lipoxin receptor agonist BML-111 on the NLRP3 inflammasome after traumatic brain injury in rats.Methods:Sixty male Sprague-Dawley rats,weighing 280~340 g,were randomly divided into 4 groups(n=15):the sham operation group(group Sham),the traumatic brain injury group(group TBI),the BML-111 treatment group(group BML-111),and the BOC-2 treatment group(group BOC-2).The TBI model was prepared by craniocerebral collision,while the rats in group Sham underwent only craniotomy without collision.Acute traumatic brain injury model was prepared in group TBI,BML-111 and BOC-2.The rats in group BOC-2 were intraperitoneally injected with 50μg/kg of BOC-230 min prior to trauma.Then the rats in group BOC-2 and BML-111 were injected intraperitoneally with 1 mg/kg of BML-111 immediately and 24 hours after trauma.The neurological severity scores(NSS)were evaluated at 3 and 7 days after brain trauma.The protein expression levels of NLRP3,Caspase-1-p20 and active Caspase-3 were determined by Western blot.The content of IL-1βand IL-18 was detected by ELISA assays.The apoptotic cells were analyzed by the TUNEL method.Results:Compared with group Sham,the brain water content and NSS scores in group TBI were increased,and the protein levels of NLRP3,Caspase-1-p20,activated Caspase-3,IL-1βand IL-18 as well as TUNEL-positive cells in the cortex were elevated significantly(P<0.05);compared with group TBI,the brain water content and NSS scores in group BML-111 were reduced,and the protein levels of NLRP3,Caspase-1-p20,activated Caspase-3,IL-1βand IL-18 as well as TUNEL-positive cells in the cortex were decreased(P<0.05);Compared with group BML-111,the brain water content and NSS scores in group BOC-2 were increased,and the protein levels of NLRP3,Caspase-1-p20,activated Caspase-3,IL-1βand IL-18 as well as TUNEL-positive cells in the cortex were up-regulated(P<0.05).Conclusions:The lipoxin receptor agonist BML-111 might attenuate traumatic brain injury in rats by inhibiting NLRP3 inflammasome activation.展开更多
Tumor-induced osteomalacia(TIO)is a rare paraneoplastic syndrome caused by excessive fibroblast growth factor 23(FGF23)production by a tumor,which often arises from a mesenchymal origin.[1-3]Most clinical symptoms of ...Tumor-induced osteomalacia(TIO)is a rare paraneoplastic syndrome caused by excessive fibroblast growth factor 23(FGF23)production by a tumor,which often arises from a mesenchymal origin.[1-3]Most clinical symptoms of TIO are the consequences of prolonged FGF23-mediated hypophosphatemia as muscle weakness,bone pain,impaired mobility,and fractures.[4]Clinical diagnosis and management of TIO are challenging because knowledge about this condition is still restricted to a few specialized centers,leading to delay in diagnosis and appropriate treatment.The scope of the present consensus is to provide up-to-date guidance on the assessment and treatment of TIO.展开更多
Comparisons of large igneous provinces(UPs)and black shales from different cratons can provide important constraints on Precambrian paleogeographic reconstructions and a better understanding of the environmental effec...Comparisons of large igneous provinces(UPs)and black shales from different cratons can provide important constraints on Precambrian paleogeographic reconstructions and a better understanding of the environmental effects of large-scale volcanic events.A comparison of intraplate mafic events mostly interpreted as LIPs or portions of LIPs(LIP fragments/remnants due to continental breakup or erosion)from the North China Craton(NCC)and North Australian Craton(NAC)shows good correlation in the age range from 1800 Ma to 1300 Ma,and four robust age matches at ca.1790-1770 Ma,ca.1730 Ma,ca.1680-1670 Ma and ca.1320 Ma have been identified.Most notably,the coeval ca.1320 Ma Yanliao LIP in the eastern-northern NCC and the Derim Derim-Galiwinku LIP in the NAC are also characterized by similar field occurences and dominantly subalkaline tholeiitic basalts and intraplate geochemical compositions,and are interpreted as portions of the same LIP,separated by continental breakup.Subsequent to 1300 Ma,the NCC and NAC exhibit very different magmatic histories,indicating that separation of these two cratons occurred,likely subsequent to the ca.1320 Ma LIP event.A comparison of Paleo-Mesoproterozoic black shales from the NCC and NAC provides further evidence for close connections between these regions during this period.Black shales of the Chuanlianggou Formation in the northern NCC and the Cuizhuang Formation in the southern NCC were deposited in the age range ca.1650-1635 Ma and can be correlated with ca.1640-1635 Ma black shales in the Barney Creek Formation of the NAC.Deposition of black shales within the Xiamaling Formation in the NCC and the Velkerri and Kyalla formations of the McArthur Basin in the NAC occurred synchronously at ca.1380-1360 Ma.Our results from matching of LIP ages and black shales combined with paleomagnetic data show that the northern-northeastern margin of the NCC was connected to the northern margin of the NAC from ca.1800 Ma to 1300 Ma.This long-lived late Paleoproterozoic to mid-Mesoproterozoic connection lasted for at least 500 million years until separation of the NCC from the NAC between ca.1320 and ca.1230-1220 Ma.展开更多
Background: Ankylosing spondylitis (AS) is the most common rheumatic condition that is slowly progressive and predominantly affects adolescents. Pathological bone formation associated with AS is an important cause ...Background: Ankylosing spondylitis (AS) is the most common rheumatic condition that is slowly progressive and predominantly affects adolescents. Pathological bone formation associated with AS is an important cause of disability. The aim of the study was to investigate the possible involvement of the genes related to endochondral ossification and ectopia ossification in genetic susceptibility to AS in a Chinese Han population. Methods: Sixty-eight single nucleotide polymorphisms (SNPs) from 13 genes were genotyped in discovery cohorts including 300 AS patients and 180 healthy controls. The rs10019009 in dentin matrix protein 1 (DMP1) gene shown as association with AS after multiple testing corrections in discovery cohorts was replicated in a validation independent cohort of 620 AS patients and 683 healthy controls. The rs 10019009 was assessed with bioin fomlatics including phylogenetic context, F-SNP and FastSNP functional predictions, secondary structure prediction, and molecular modeling. We performed a functional analysis of rs10019009 via reverse transcription-polymerase chain reaction, alkaline phosphatase (ALP) activity in human osteosarcoma U2OS cells. Results: Interestingly, the SNP rs10019009 was associated with AS in both the discovery cohort (P = 0.0012) and validation cohort (P - 0.0349), as well as overall (P = 0.0004) in genetic case-control association analysis. After a multivariate logistic regression analysis, the effect of this genetic variant was observed to be independent of linkage disequilibrium. Via bioinformatics analysis, it was found that the amino acid change of the rs 10019009 led to changes of SNP function, secondary structure, tertiary confomlation, and splice mode. Finally, functional analysis ofrsl0019009 in U2OS cells demonstrated that the risk T allele of the rsl0019009 increased enzymatic activity of ALP, compared to that of the nonrisk allele (P = 0.0080). Conclusions: These results suggested that the DMP1 gene seems to be involved in genetic predisposition to AS, which may contribute to the ectopic mineralization or ossification in AS. In addition, DMP1 gene may be a promising intervention target for AS in the future.展开更多
文摘AIM: To evaluate the efficacy and toxicity of stereotactic body radiotherapy using Cyber Knife for locally advanced unresectable and metastatic pancreatic cancer.METHODS: From June 2010 to May 2014,25 patients with locally advanced unresectable and metastatic pancreatic cancer underwent stereotactic body radiotherapy.Nine patients presented with unresectable locally advanced disease and 16 had metastatic disease.Primary end-points of this study were overall survival,relief of abdominal pain,and toxicity.RESULTS: Fourteen patients were treated with a total dose of 30-36 Gy in three fractions and the remainder with 40-48 Gy in four fractions.Median follow-up was 11 mo(range: 2-25 mo).The median survival duration calculated from the time of stereotactic body radiotherapy for the entire group,the locally advanced group,and the metastatic group was 9.0 mo,13.5 mo,and 8.5 mo,respectively.Overall survival was 37% and 18% at one and two years,respectively.Abdominal pain relief was achieved within 2 wk of completing radiotherapy in the patients who received successful palliation(13 of 20 patients had significant pain).Five patients(20%) had grade 1 nausea,and one(4%) had grade 2 nausea.No acute grade 3+ toxicity was seen.CONCLUSION: Stereotactic body radiotherapy using the Cyber Knife system is a promising,noninvasive,palliative treatment with acceptable toxicity for locally advanced unresectable and metastatic pancreatic cancer.
基金supported by grants from the National Natural Science Foundation of China(81071030)the Science and Technology Foundation of Guangdong Province(2011B080701006)
文摘BACKGROUND:Early reperfusion can effectively treat acute myocardial infarction(AMI) and reduce the mortality signif icantly. This study aimed to compare the role of plasma microRNA-1(miR-1) and cardiac troponin T(cTnT) in early diagnosis of AMI patients.METHODS:From May 2011 to May 2012,plasma samples were collected from 56 AMI patients and 28 non-AMI controls. The expression of plasma miR-1 was measured by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),and the level of plasma cTnT was measured using electrochemiluminescence-based methods on an Elecsys 2010 Immunoassay Analyzer. SPSS 16.0 was used for the statistical analysis of the results. Data were expressed as mean±standard deviation unless otherwise described. The differences about clinical characteristics between the AMI patients and controls were tested using Student's t test or Fisher's exact test. The Mann-Whitney U test was conducted to compare the expression of microRNAs between the AMI patients and controls. MicroRNAs expression between different intervals of the AMI patients was compared using Wilcoxon's signed-rank test. The receiver operating characteristic(ROC) curve was established to discriminate the AMI patients from the controls.RESULTS:In the present study,the expression of plasma miR-1 was signifi cantly increased in the AMI patients compared with the healthy controls(P<0.01). The plasma miR-1 in the AMI patients decreased to the normal level at 14 days(P>0.05). The expression of plasma miR-1 was not related to the clinical characteristics of the study population(P>0.05). ROC curve analyses demonstrated that miR-1 was specifi c and sensitive for the early diagnosis of AMI,but not superior to cTnT.CONCLUSION:Plasma miR-1 could be used in the early diagnosis of AMI,but it is similar to cTnT.
基金supported by projects from the National Natural Science Foundation of China(81370977,81570796 and 81370018)by the Shanghai Science and Technology Committee(14411960900)
文摘Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin (OCN) in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen (CTX) and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant (NGT) women at baseline were invited for follow-up. The incidence of diabetes and prediabetes (collectively defined as dysglycemia) was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% (95% confidence interval (CI), 6.8%-30.70/0)] compared with the lower [31.0% (95% CI, 17.2%-46.1%)] and upper [46.5% (95% CI, 31.2%-62.6%)] tertiles of CTX, with a significant difference seen between the middle and upper tertiles (P = 0.002 5). After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 (95% CI, 1.73-28.99) when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.
基金supported by a grant from the NIH:DK32333supported by the National Natural Science Foundation of China (81070693 and 81200647)
文摘In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism (PHPT) changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT con- tinues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.
文摘Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.
文摘Objective:To investigate the effect of lipoxin receptor agonist BML-111 on the NLRP3 inflammasome after traumatic brain injury in rats.Methods:Sixty male Sprague-Dawley rats,weighing 280~340 g,were randomly divided into 4 groups(n=15):the sham operation group(group Sham),the traumatic brain injury group(group TBI),the BML-111 treatment group(group BML-111),and the BOC-2 treatment group(group BOC-2).The TBI model was prepared by craniocerebral collision,while the rats in group Sham underwent only craniotomy without collision.Acute traumatic brain injury model was prepared in group TBI,BML-111 and BOC-2.The rats in group BOC-2 were intraperitoneally injected with 50μg/kg of BOC-230 min prior to trauma.Then the rats in group BOC-2 and BML-111 were injected intraperitoneally with 1 mg/kg of BML-111 immediately and 24 hours after trauma.The neurological severity scores(NSS)were evaluated at 3 and 7 days after brain trauma.The protein expression levels of NLRP3,Caspase-1-p20 and active Caspase-3 were determined by Western blot.The content of IL-1βand IL-18 was detected by ELISA assays.The apoptotic cells were analyzed by the TUNEL method.Results:Compared with group Sham,the brain water content and NSS scores in group TBI were increased,and the protein levels of NLRP3,Caspase-1-p20,activated Caspase-3,IL-1βand IL-18 as well as TUNEL-positive cells in the cortex were elevated significantly(P<0.05);compared with group TBI,the brain water content and NSS scores in group BML-111 were reduced,and the protein levels of NLRP3,Caspase-1-p20,activated Caspase-3,IL-1βand IL-18 as well as TUNEL-positive cells in the cortex were decreased(P<0.05);Compared with group BML-111,the brain water content and NSS scores in group BOC-2 were increased,and the protein levels of NLRP3,Caspase-1-p20,activated Caspase-3,IL-1βand IL-18 as well as TUNEL-positive cells in the cortex were up-regulated(P<0.05).Conclusions:The lipoxin receptor agonist BML-111 might attenuate traumatic brain injury in rats by inhibiting NLRP3 inflammasome activation.
基金by grants from the CAMS Innovation Fund for Medical Science(No.2016-I2M-3-003)the National Natural Science Foundation of China(No.81970757 and No.81670714).
文摘Tumor-induced osteomalacia(TIO)is a rare paraneoplastic syndrome caused by excessive fibroblast growth factor 23(FGF23)production by a tumor,which often arises from a mesenchymal origin.[1-3]Most clinical symptoms of TIO are the consequences of prolonged FGF23-mediated hypophosphatemia as muscle weakness,bone pain,impaired mobility,and fractures.[4]Clinical diagnosis and management of TIO are challenging because knowledge about this condition is still restricted to a few specialized centers,leading to delay in diagnosis and appropriate treatment.The scope of the present consensus is to provide up-to-date guidance on the assessment and treatment of TIO.
基金the National Natural Science Foundation of China(Grants No.41725011,41920104004)the National Key Research and Development Project of China(Grant No.2020YFA0714803)+1 种基金REE was partially supported by Russian Mega-Grant(Grant No.14.Y26.31.0012)We are grateful to Darryl Stacey and Shannon Walsh(both NTGS)for help during drill core sample collecting in Darwin,Australia.The manuscript has benefited from thoughtful and constructive reviews by two anonymous reviewers,which significantly improved the quality of our paper.Tim Munson publishes with the permission of the Executive Director,Northern Territory Geological Survey.
文摘Comparisons of large igneous provinces(UPs)and black shales from different cratons can provide important constraints on Precambrian paleogeographic reconstructions and a better understanding of the environmental effects of large-scale volcanic events.A comparison of intraplate mafic events mostly interpreted as LIPs or portions of LIPs(LIP fragments/remnants due to continental breakup or erosion)from the North China Craton(NCC)and North Australian Craton(NAC)shows good correlation in the age range from 1800 Ma to 1300 Ma,and four robust age matches at ca.1790-1770 Ma,ca.1730 Ma,ca.1680-1670 Ma and ca.1320 Ma have been identified.Most notably,the coeval ca.1320 Ma Yanliao LIP in the eastern-northern NCC and the Derim Derim-Galiwinku LIP in the NAC are also characterized by similar field occurences and dominantly subalkaline tholeiitic basalts and intraplate geochemical compositions,and are interpreted as portions of the same LIP,separated by continental breakup.Subsequent to 1300 Ma,the NCC and NAC exhibit very different magmatic histories,indicating that separation of these two cratons occurred,likely subsequent to the ca.1320 Ma LIP event.A comparison of Paleo-Mesoproterozoic black shales from the NCC and NAC provides further evidence for close connections between these regions during this period.Black shales of the Chuanlianggou Formation in the northern NCC and the Cuizhuang Formation in the southern NCC were deposited in the age range ca.1650-1635 Ma and can be correlated with ca.1640-1635 Ma black shales in the Barney Creek Formation of the NAC.Deposition of black shales within the Xiamaling Formation in the NCC and the Velkerri and Kyalla formations of the McArthur Basin in the NAC occurred synchronously at ca.1380-1360 Ma.Our results from matching of LIP ages and black shales combined with paleomagnetic data show that the northern-northeastern margin of the NCC was connected to the northern margin of the NAC from ca.1800 Ma to 1300 Ma.This long-lived late Paleoproterozoic to mid-Mesoproterozoic connection lasted for at least 500 million years until separation of the NCC from the NAC between ca.1320 and ca.1230-1220 Ma.
基金This study was supported by grants from the National Natural Science Foundation of China,the Natural Science Foundation of Liaoning Province
文摘Background: Ankylosing spondylitis (AS) is the most common rheumatic condition that is slowly progressive and predominantly affects adolescents. Pathological bone formation associated with AS is an important cause of disability. The aim of the study was to investigate the possible involvement of the genes related to endochondral ossification and ectopia ossification in genetic susceptibility to AS in a Chinese Han population. Methods: Sixty-eight single nucleotide polymorphisms (SNPs) from 13 genes were genotyped in discovery cohorts including 300 AS patients and 180 healthy controls. The rs10019009 in dentin matrix protein 1 (DMP1) gene shown as association with AS after multiple testing corrections in discovery cohorts was replicated in a validation independent cohort of 620 AS patients and 683 healthy controls. The rs 10019009 was assessed with bioin fomlatics including phylogenetic context, F-SNP and FastSNP functional predictions, secondary structure prediction, and molecular modeling. We performed a functional analysis of rs10019009 via reverse transcription-polymerase chain reaction, alkaline phosphatase (ALP) activity in human osteosarcoma U2OS cells. Results: Interestingly, the SNP rs10019009 was associated with AS in both the discovery cohort (P = 0.0012) and validation cohort (P - 0.0349), as well as overall (P = 0.0004) in genetic case-control association analysis. After a multivariate logistic regression analysis, the effect of this genetic variant was observed to be independent of linkage disequilibrium. Via bioinformatics analysis, it was found that the amino acid change of the rs 10019009 led to changes of SNP function, secondary structure, tertiary confomlation, and splice mode. Finally, functional analysis ofrsl0019009 in U2OS cells demonstrated that the risk T allele of the rsl0019009 increased enzymatic activity of ALP, compared to that of the nonrisk allele (P = 0.0080). Conclusions: These results suggested that the DMP1 gene seems to be involved in genetic predisposition to AS, which may contribute to the ectopic mineralization or ossification in AS. In addition, DMP1 gene may be a promising intervention target for AS in the future.