The Duolong mineral district in western Tibet is one of the largest porphyry Cu–Au deposit fields with significant metallogenic potential in China.Its tectonic environment relevant to Early Cretaceous Cu–Au minerali...The Duolong mineral district in western Tibet is one of the largest porphyry Cu–Au deposit fields with significant metallogenic potential in China.Its tectonic environment relevant to Early Cretaceous Cu–Au mineralization remains controversial.Here we report new whole-rock major and trace element,and Sr-Nd-Hf-Pb isotopic data for the newly discovered basalt in the Nadun area,Duolong mineral district,to decipher their genesis and further constrain the tectonic environment.A contemporaneous rhyolite sample interbedded with the basalt in the lower part of the volcanic section in the Nadun area yields an LA-ICP-MS zircon U–Pb age of 122.5±1.2 Ma.The basalt samples exhibit high-K calc-alkaline/shoshonite properties and are enriched in high field strength elements,e.g.,high Ti O_(2)(1.43–1.79 wt.%)and Nb(14.6–19.5 ppm)contents,with high Nb/La ratios(0.4–0.6),which are compositionally comparable to those of Nb-enriched arc basalts(NEABs).The(^(87) Sr/^(86) Sr)iratios of 0.7052 to 0.7056,negative eNd(t)(-0.7 to-0.2)and eHf(t)values(+6.0 to+6.5),and high(^(206) Pb/^(204)Pb)i,(^(207) Pb/^(204)Pb)i,(^(208) Pb/^(204)Pb)iand ratios(18.522 to 18.561,15.641 to 15.645 and 38.679 to 38.730,respectively)suggest that the Nadun NEABs are more enriched than those of the island arc basalts(IABs)in the area.The slightly enriched radiogenic isotopes for the Nadun NEABs indicate that the subducting sediments play an important role in the source.Furthermore,their high Nb,Ti,and Cu contents indicate that the source mantle wedge was metasomatized by slab melts.The Nadun NEAB and other coeval magmatic rocks in the Duolong mineral district,including adakite,OIB-like basalt,MORB-type basalt,A-type rhyolite,and common IAB,are typical rock assemblages of ridge subduction.We infer that the Duolong mineral district were formed by ridge subduction in the Early Cretaceous.展开更多
Seamounts on the drifting oceanic crust are inevitably carried by plate motions and eventually accreted or subducted.However,the geochemical signatures of the subducted seamounts and the significance of seamount subdu...Seamounts on the drifting oceanic crust are inevitably carried by plate motions and eventually accreted or subducted.However,the geochemical signatures of the subducted seamounts and the significance of seamount subduction are not well constrained.Hundreds of seamounts have subducted beneath the Philippine Sea Plate following the westward subduction of the Pacific Plate since the Eocene(~52 Ma).The subducted oceanic crust and seamount materials can be exhumed from the mantle depth to the seafloor in the Mariana forearc region by serpentinite mud volcanoes,providing exceptional opportunities to directly study the subducted oceanic crust and seamounts.The International Ocean Discovery Program(IODP)expedition 366 has recovered a few metamorphosed mafic clasts exhumed from the Mariana forearc serpentinite mud volcanoes,e.g.,the Fantangis?a and Asùt Tesoru seamounts.These mafic clasts have tholeiitic to alkaline affinities with distinct trace elements and Nd-Hf isotopes characteristics,suggesting different provenances and mantle sources.The tholeiites from the Fantangisna Seamount have trace element characteristics typical of mid-ocean ridge basalt.The Pacific-type Hf-Nd isotopic compositions,combined with the greenschist metamorphism of these tholeiites further suggest that they came from the subducted Pacific oceanic crust.The alkali basalts-dolerites from the Fantangisna and Asùt Tesoru seamounts show ocean island basalt(OIB)-like geochemical characteristics.The OIB-like geochemical signatures and the low-grade metamorphism of these alkali basalts-dolerites suggest they came from subducted seamounts that originally formed in an intraplate setting on the Pacific Plate.The Pacific Plate origin of these metabasites suggests they were formed in the Early Cretaceous or earlier.Two types of OIBs have been recognized from alkali metabasites,one of which is geochemically similar to the HIMU-EMI-type OIBs from the West Pacific Seamount Province,and another is similar to the EMII-type OIBs from the Samoa Island in southern Pacific,with negative Nb-Ta-Ti anomalies and enriched Nd-Hf isotopes.Generally,these alkali metabasites are sourced from the heterogeneous mantle sources that are similar to the present South Pacific Isotopic and Thermal Anomaly.This study provides direct evidence for seamount subduction in the Mariana convergent margins.We suggest seamount subduction is significant to element cycling,mantle heterogeneity,and mantle oxidation in subduction zones.展开更多
Importance:Systemic lupus erythematosus(SLE)is a diffuse connective tissue disease with complex clinical manifestations and prolonged course.The early diagnosis and condition monitoring of SLE are crucial to disease p...Importance:Systemic lupus erythematosus(SLE)is a diffuse connective tissue disease with complex clinical manifestations and prolonged course.The early diagnosis and condition monitoring of SLE are crucial to disease prognosis.Objective:To assess the diagnostic value of long noncoding RNA(lncRNA)nuclear enriched abundant transcript 1(NEAT1)in childhood-onset SLE(cSLE).Methods:Fifty-seven children diagnosed with SLE,40 children diagnosed with juvenile idiopathic arthritis(JIA),and 40 healthy children were included.Peripheral blood samples from each patient were collected.A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT1_1 and lncNEAT1_2 in peripheral blood.Associations among parameters were analyzed using the Mann-Whitney U test or independent sample t-test.Results:The expression of both lncNEAT1_1 and lncNEAT1_2 in patients with cSLE were significantly higher than that of healthy control and patients with JIA.Receiver operating characteristic curves revealed an area under the curve(AUC)of 0.633(95%confidence interval[CI],0.524-0.742;P=0.024)for lncNEAT1_1.The AUC of lncNEAT1_2 was 0.812(95%CI,0.727-0.897;P<0.0001)to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of 0.925.Moreover,lncNEAT1_2 expression was higher in patients with cSLE presenting with fever,lupus nephritis,elevated erythrocyte sedimentation rate,active disease activity,and decreased C3 level,compared with those without these conditions.However,no similar correlation was observed for lncNEAT1_1.Interpretation:The expression of lncNEAT1_2 was significantly elevated in children with SLE,especially those with fever,renal involvement,and low C3 levels.These findings suggest that lncNEAT1_2 may represent a potential biomarker for cSLE.展开更多
Background:Circular RNA (circRNA) plays an important role in the pathogenesis of many diseases and can be used as a biomarker for diagnosis or disease monitoring. However, reports on circRNA in childhood-onset systemi...Background:Circular RNA (circRNA) plays an important role in the pathogenesis of many diseases and can be used as a biomarker for diagnosis or disease monitoring. However, reports on circRNA in childhood-onset systemic lupus erythematosus (cSLE) are limited. Therefore, this study aimed to investigate circEPSTI1 expression in cSLE and evaluate its potential as a biomarker for diagnosing cSLE.Methods:This study included 70 children diagnosed with cSLE, 20 diagnosed with juvenile idiopathic arthritis (JIA), 20 diagnosed with juvenile dermatomyositis (JDM), and 50 healthy children at the Rheumatology Department of Beijing Children's Hospital from January 2019 to December 2019. Quantitative polymerase chain reaction was used to determine circEPSTI1 expression in the children. Correlations between circEPSTI1 and clinical features were assessed using Spearman's correlation test. Additionally, we calculated the receiver operating characteristic curve to assess the diagnostic efficacy.Results:We found that circEPSTI1 expression was higher in children with cSLE (4.62 ± 3.55) than that in healthy children (1.00 ± 0.45), those with JDM (1.06 ± 0.76), and those with JIA (0.96 ± 0.48). The area of the curve of circEPSTI1 was 0.892 (95% confidence interval [CI]: 0.832-0.952, p < 0.001) to discriminate children with SLE from healthy children, with a specificity of 0.814 and a sensitivity of 0.922. Children with lupus nephritis showed a higher circEPSTI1 expression than healthy children, those with JDM, and those with JIA. In addition, circEPSTI1 expression in children with SLE showed significant correlations with the SLE Disease Activity Index ( p < 0.0001) and C3 concentrations ( p = 0.001). Conclusion:Our study suggests that circEPSTI1 is a promising biomarker for the diagnosis and monitoring of cSLE.展开更多
To the Editor,Blau syndrome(BS)is a rare autosomal dominant disorder that occurs early in childhood.It is caused by mutations in nucleotide-binding oligomerization domain-containing protein 2(NOD2),also known as caspa...To the Editor,Blau syndrome(BS)is a rare autosomal dominant disorder that occurs early in childhood.It is caused by mutations in nucleotide-binding oligomerization domain-containing protein 2(NOD2),also known as caspase activation and recruitment domain 15(CARD15).NOD2 mutations result in the activation of nuclear factor-kappa B and induction inflammation.1 Some patients develop the disease in a familial manner,but sporadic cases can occur.The main clinical manifestations of BS are the triad of rash,arthritis,and iridocyclitis,while multiple aortitis,deafness,heart disease,liver,spleen,and central nervous system are also involved.2 The disease was first described by Dr.Blau in 1985.展开更多
To improve the power-extraction performance of the Savonius vertical-axis wind turbine(S-VAWT),additional cylinders,which are used to control the fluid flow around the wind turbine blade,were introduced into the blade...To improve the power-extraction performance of the Savonius vertical-axis wind turbine(S-VAWT),additional cylinders,which are used to control the fluid flow around the wind turbine blade,were introduced into the blade design.In contrast to the traditional numerical method,a mathematical model in the form of a dynamical system was used in this study.A numerical calculation program that could effectively solve the equations of wind-induced rotation of S-VAWT was developed,and combined with the Taguchi experimental method to investigate the influence of additional cylinders on the power-extraction characteristics of the S-VAWT.The results showed that the additional cylinders have a significant impact on the power-extraction performance of the S-VAWT.At 4-m/s wind speed,the average power coefficient of the S-VAWT with additional cylinders is 15%higher than that of the conventional S-VAWT.After construction of the wind turbine prototype and power-extraction tests,the results showed that compared with a conventional S-VAWT,the output power was 29%higher for the S-VAWT with additional cylinders under the same particular conditions.展开更多
The aim of our study is to explore the features of clinical manifestations and genetic mutations in Chinese CAPS patients. Fifteen confirmed patients with CAPS were enrolled. The onset time ranges from 2 days after bi...The aim of our study is to explore the features of clinical manifestations and genetic mutations in Chinese CAPS patients. Fifteen confirmed patients with CAPS were enrolled. The onset time ranges from 2 days after birth to 6 years and 1 month. Recurrent urticaria rash(93.3%) with fever(100%) were two dominant characteristics of these patients that were presented as either acute or chronic process. Systemic involvements were found in all patients except for one with only rash and fever. The top three symptoms were fever(100%), rash(93.3%) and myalgia(76%). Other clinical manifestations include arthritis(11 cases), lung involvement(seven cases), optical dysfunction(seven cases), nerve deafness(six cases), nervous system involvement(five cases), hepatomegaly, splenomegaly and lymphadenectasis(five cases). Also, four patients had heart involvement and one patient suffered kidney involvement. The laboratory inflammation index such as leukocyte counts, platelet counts, erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), serum amyloid A(SAA) and fibrinogen(FIB) increased significantly at initial stage, but decreased after therapy. As for gene mutation detection, Twelve out of 15 patients were confirmed with mutation in NLRP3, including 11 mutant site: c1789 A>G, c.1703 T>A, c.913 G>A, c.1710 G>C, c.1057 G >T, c.2335 C>T, c.932 T>C,c.296 G>C, c.663 C>T, t.1702 T>A, 299 G>A. Mutation sites c.1703 T>A, c.2335 C>T, c.296 G>C, c.663 C>T, and 299 G>A were newly identified. The association between gene mutation and clinical manifestation shows that D305 N was highly associated with severe organs involvements, and therefore, the time of therapy and regimen were critical for the prognosis of disease. As the largest cohort study of Chinese CAPS patients, we confirmed that all patients presented typical clinical manifestations, identified five new mutation sites on NLRP3 and analyzed the correlation between the genotypes and phenotypes. We also raise concerns for one case with serious conditions that only had two nonsense mutations(c.663 C>T and t.1702 T>A) detected.展开更多
The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified10 missense mutations, out of which five were new: R334 L, E383 D, R471 C, C495 R and D512 F. The r...The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified10 missense mutations, out of which five were new: R334 L, E383 D, R471 C, C495 R and D512 F. The rest of them, R334 W,R334Q, G481 D, M513 T and R587 C, have been reported previously. Among all the mutations, R334 W, R334 Q and C495 R had the highest frequency. Blau syndrome was found at early age after birth. It began with lepidic rash and symmetric polyarthritis and was phenotypically characterized by typical rash, arthritis, iridocyclitis and arteritis. Cardiac involvement was also found in Blau syndrome. In addition to nerve deafness, renal involvement, osteochondroma and central nervous system involvement were also found in our patients. Therefore, Chinese children with Blau syndrome have unique gene mutations and complicated clinical phenotypes. Pathologic examination and CARD15 mutation testing should be considered for diagnosis as early as possible for suspected patients.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.42002235,41803002)the National Key R&D Program of China(2016YFC0600408)+3 种基金the China Postdoctoral Science Foundation(Grant Nos.2019M652495,2018M642708)the Taishan Scholar Program of Shandong(ts201712075)the Ao Shan Talents Cultivation Program Supported by Qingdao National Laboratory for Marine Science and Technology(2017ASTCP-OS07)the Pilot National Laboratory for Marine Science and Technology(Qingdao)(No.JCZX202026)。
文摘The Duolong mineral district in western Tibet is one of the largest porphyry Cu–Au deposit fields with significant metallogenic potential in China.Its tectonic environment relevant to Early Cretaceous Cu–Au mineralization remains controversial.Here we report new whole-rock major and trace element,and Sr-Nd-Hf-Pb isotopic data for the newly discovered basalt in the Nadun area,Duolong mineral district,to decipher their genesis and further constrain the tectonic environment.A contemporaneous rhyolite sample interbedded with the basalt in the lower part of the volcanic section in the Nadun area yields an LA-ICP-MS zircon U–Pb age of 122.5±1.2 Ma.The basalt samples exhibit high-K calc-alkaline/shoshonite properties and are enriched in high field strength elements,e.g.,high Ti O_(2)(1.43–1.79 wt.%)and Nb(14.6–19.5 ppm)contents,with high Nb/La ratios(0.4–0.6),which are compositionally comparable to those of Nb-enriched arc basalts(NEABs).The(^(87) Sr/^(86) Sr)iratios of 0.7052 to 0.7056,negative eNd(t)(-0.7 to-0.2)and eHf(t)values(+6.0 to+6.5),and high(^(206) Pb/^(204)Pb)i,(^(207) Pb/^(204)Pb)i,(^(208) Pb/^(204)Pb)iand ratios(18.522 to 18.561,15.641 to 15.645 and 38.679 to 38.730,respectively)suggest that the Nadun NEABs are more enriched than those of the island arc basalts(IABs)in the area.The slightly enriched radiogenic isotopes for the Nadun NEABs indicate that the subducting sediments play an important role in the source.Furthermore,their high Nb,Ti,and Cu contents indicate that the source mantle wedge was metasomatized by slab melts.The Nadun NEAB and other coeval magmatic rocks in the Duolong mineral district,including adakite,OIB-like basalt,MORB-type basalt,A-type rhyolite,and common IAB,are typical rock assemblages of ridge subduction.We infer that the Duolong mineral district were formed by ridge subduction in the Early Cretaceous.
基金financially supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA22050103,XDB42020303,XDB18020102)the National Natural Science Foundation of China(Grant No.41803002)+2 种基金China Postdoctoral Science Foundation(No.2018 M642708)the Qingdao National Laboratory for Marine Science and Technology(2017ASKJ02)the Taishan Scholar Foundation of Shandong Province(ts201712075)。
文摘Seamounts on the drifting oceanic crust are inevitably carried by plate motions and eventually accreted or subducted.However,the geochemical signatures of the subducted seamounts and the significance of seamount subduction are not well constrained.Hundreds of seamounts have subducted beneath the Philippine Sea Plate following the westward subduction of the Pacific Plate since the Eocene(~52 Ma).The subducted oceanic crust and seamount materials can be exhumed from the mantle depth to the seafloor in the Mariana forearc region by serpentinite mud volcanoes,providing exceptional opportunities to directly study the subducted oceanic crust and seamounts.The International Ocean Discovery Program(IODP)expedition 366 has recovered a few metamorphosed mafic clasts exhumed from the Mariana forearc serpentinite mud volcanoes,e.g.,the Fantangis?a and Asùt Tesoru seamounts.These mafic clasts have tholeiitic to alkaline affinities with distinct trace elements and Nd-Hf isotopes characteristics,suggesting different provenances and mantle sources.The tholeiites from the Fantangisna Seamount have trace element characteristics typical of mid-ocean ridge basalt.The Pacific-type Hf-Nd isotopic compositions,combined with the greenschist metamorphism of these tholeiites further suggest that they came from the subducted Pacific oceanic crust.The alkali basalts-dolerites from the Fantangisna and Asùt Tesoru seamounts show ocean island basalt(OIB)-like geochemical characteristics.The OIB-like geochemical signatures and the low-grade metamorphism of these alkali basalts-dolerites suggest they came from subducted seamounts that originally formed in an intraplate setting on the Pacific Plate.The Pacific Plate origin of these metabasites suggests they were formed in the Early Cretaceous or earlier.Two types of OIBs have been recognized from alkali metabasites,one of which is geochemically similar to the HIMU-EMI-type OIBs from the West Pacific Seamount Province,and another is similar to the EMII-type OIBs from the Samoa Island in southern Pacific,with negative Nb-Ta-Ti anomalies and enriched Nd-Hf isotopes.Generally,these alkali metabasites are sourced from the heterogeneous mantle sources that are similar to the present South Pacific Isotopic and Thermal Anomaly.This study provides direct evidence for seamount subduction in the Mariana convergent margins.We suggest seamount subduction is significant to element cycling,mantle heterogeneity,and mantle oxidation in subduction zones.
基金National Natural Science Foundation of China,Grant/Award Number:81701604R&D program of Beijing Municipal Education Commission,Grant/Award Number:202210025037。
文摘Importance:Systemic lupus erythematosus(SLE)is a diffuse connective tissue disease with complex clinical manifestations and prolonged course.The early diagnosis and condition monitoring of SLE are crucial to disease prognosis.Objective:To assess the diagnostic value of long noncoding RNA(lncRNA)nuclear enriched abundant transcript 1(NEAT1)in childhood-onset SLE(cSLE).Methods:Fifty-seven children diagnosed with SLE,40 children diagnosed with juvenile idiopathic arthritis(JIA),and 40 healthy children were included.Peripheral blood samples from each patient were collected.A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT1_1 and lncNEAT1_2 in peripheral blood.Associations among parameters were analyzed using the Mann-Whitney U test or independent sample t-test.Results:The expression of both lncNEAT1_1 and lncNEAT1_2 in patients with cSLE were significantly higher than that of healthy control and patients with JIA.Receiver operating characteristic curves revealed an area under the curve(AUC)of 0.633(95%confidence interval[CI],0.524-0.742;P=0.024)for lncNEAT1_1.The AUC of lncNEAT1_2 was 0.812(95%CI,0.727-0.897;P<0.0001)to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of 0.925.Moreover,lncNEAT1_2 expression was higher in patients with cSLE presenting with fever,lupus nephritis,elevated erythrocyte sedimentation rate,active disease activity,and decreased C3 level,compared with those without these conditions.However,no similar correlation was observed for lncNEAT1_1.Interpretation:The expression of lncNEAT1_2 was significantly elevated in children with SLE,especially those with fever,renal involvement,and low C3 levels.These findings suggest that lncNEAT1_2 may represent a potential biomarker for cSLE.
基金R&D program of the Beijing Municipal Education Commission(No.KZ202210025037)Beijing Hospitals Authority Youth Program(No.QMS 20191202).
文摘Background:Circular RNA (circRNA) plays an important role in the pathogenesis of many diseases and can be used as a biomarker for diagnosis or disease monitoring. However, reports on circRNA in childhood-onset systemic lupus erythematosus (cSLE) are limited. Therefore, this study aimed to investigate circEPSTI1 expression in cSLE and evaluate its potential as a biomarker for diagnosing cSLE.Methods:This study included 70 children diagnosed with cSLE, 20 diagnosed with juvenile idiopathic arthritis (JIA), 20 diagnosed with juvenile dermatomyositis (JDM), and 50 healthy children at the Rheumatology Department of Beijing Children's Hospital from January 2019 to December 2019. Quantitative polymerase chain reaction was used to determine circEPSTI1 expression in the children. Correlations between circEPSTI1 and clinical features were assessed using Spearman's correlation test. Additionally, we calculated the receiver operating characteristic curve to assess the diagnostic efficacy.Results:We found that circEPSTI1 expression was higher in children with cSLE (4.62 ± 3.55) than that in healthy children (1.00 ± 0.45), those with JDM (1.06 ± 0.76), and those with JIA (0.96 ± 0.48). The area of the curve of circEPSTI1 was 0.892 (95% confidence interval [CI]: 0.832-0.952, p < 0.001) to discriminate children with SLE from healthy children, with a specificity of 0.814 and a sensitivity of 0.922. Children with lupus nephritis showed a higher circEPSTI1 expression than healthy children, those with JDM, and those with JIA. In addition, circEPSTI1 expression in children with SLE showed significant correlations with the SLE Disease Activity Index ( p < 0.0001) and C3 concentrations ( p = 0.001). Conclusion:Our study suggests that circEPSTI1 is a promising biomarker for the diagnosis and monitoring of cSLE.
基金Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority,Grand/Award Number:XTCX201819National Regional Medical Center Opening Project,Grand/Award Number:NRMC0110BCH Young Investigator Program(BCHYIP),Grant/Award Number:BCHYIP-3-39.
文摘To the Editor,Blau syndrome(BS)is a rare autosomal dominant disorder that occurs early in childhood.It is caused by mutations in nucleotide-binding oligomerization domain-containing protein 2(NOD2),also known as caspase activation and recruitment domain 15(CARD15).NOD2 mutations result in the activation of nuclear factor-kappa B and induction inflammation.1 Some patients develop the disease in a familial manner,but sporadic cases can occur.The main clinical manifestations of BS are the triad of rash,arthritis,and iridocyclitis,while multiple aortitis,deafness,heart disease,liver,spleen,and central nervous system are also involved.2 The disease was first described by Dr.Blau in 1985.
基金This work is supported by the National Natural Science Foundation of China(No.51975429).
文摘To improve the power-extraction performance of the Savonius vertical-axis wind turbine(S-VAWT),additional cylinders,which are used to control the fluid flow around the wind turbine blade,were introduced into the blade design.In contrast to the traditional numerical method,a mathematical model in the form of a dynamical system was used in this study.A numerical calculation program that could effectively solve the equations of wind-induced rotation of S-VAWT was developed,and combined with the Taguchi experimental method to investigate the influence of additional cylinders on the power-extraction characteristics of the S-VAWT.The results showed that the additional cylinders have a significant impact on the power-extraction performance of the S-VAWT.At 4-m/s wind speed,the average power coefficient of the S-VAWT with additional cylinders is 15%higher than that of the conventional S-VAWT.After construction of the wind turbine prototype and power-extraction tests,the results showed that compared with a conventional S-VAWT,the output power was 29%higher for the S-VAWT with additional cylinders under the same particular conditions.
基金supported by special fund for clinical medicine of Chinese Medical Association(12040690369)
文摘The aim of our study is to explore the features of clinical manifestations and genetic mutations in Chinese CAPS patients. Fifteen confirmed patients with CAPS were enrolled. The onset time ranges from 2 days after birth to 6 years and 1 month. Recurrent urticaria rash(93.3%) with fever(100%) were two dominant characteristics of these patients that were presented as either acute or chronic process. Systemic involvements were found in all patients except for one with only rash and fever. The top three symptoms were fever(100%), rash(93.3%) and myalgia(76%). Other clinical manifestations include arthritis(11 cases), lung involvement(seven cases), optical dysfunction(seven cases), nerve deafness(six cases), nervous system involvement(five cases), hepatomegaly, splenomegaly and lymphadenectasis(five cases). Also, four patients had heart involvement and one patient suffered kidney involvement. The laboratory inflammation index such as leukocyte counts, platelet counts, erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), serum amyloid A(SAA) and fibrinogen(FIB) increased significantly at initial stage, but decreased after therapy. As for gene mutation detection, Twelve out of 15 patients were confirmed with mutation in NLRP3, including 11 mutant site: c1789 A>G, c.1703 T>A, c.913 G>A, c.1710 G>C, c.1057 G >T, c.2335 C>T, c.932 T>C,c.296 G>C, c.663 C>T, t.1702 T>A, 299 G>A. Mutation sites c.1703 T>A, c.2335 C>T, c.296 G>C, c.663 C>T, and 299 G>A were newly identified. The association between gene mutation and clinical manifestation shows that D305 N was highly associated with severe organs involvements, and therefore, the time of therapy and regimen were critical for the prognosis of disease. As the largest cohort study of Chinese CAPS patients, we confirmed that all patients presented typical clinical manifestations, identified five new mutation sites on NLRP3 and analyzed the correlation between the genotypes and phenotypes. We also raise concerns for one case with serious conditions that only had two nonsense mutations(c.663 C>T and t.1702 T>A) detected.
基金supported by Special Fund for Clinical Medicine of Chinese Medical Association (12040690369)
文摘The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified10 missense mutations, out of which five were new: R334 L, E383 D, R471 C, C495 R and D512 F. The rest of them, R334 W,R334Q, G481 D, M513 T and R587 C, have been reported previously. Among all the mutations, R334 W, R334 Q and C495 R had the highest frequency. Blau syndrome was found at early age after birth. It began with lepidic rash and symmetric polyarthritis and was phenotypically characterized by typical rash, arthritis, iridocyclitis and arteritis. Cardiac involvement was also found in Blau syndrome. In addition to nerve deafness, renal involvement, osteochondroma and central nervous system involvement were also found in our patients. Therefore, Chinese children with Blau syndrome have unique gene mutations and complicated clinical phenotypes. Pathologic examination and CARD15 mutation testing should be considered for diagnosis as early as possible for suspected patients.