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 nonsen展开更多
Background： Restrictive cardiomyopathy （RCM） is the least common cardiomyopathy in which the walls are rigid and the heart is restricted from stretching and filling properly. Cardiac troponin I （cTnI） mutation-ca...Background： Restrictive cardiomyopathy （RCM） is the least common cardiomyopathy in which the walls are rigid and the heart is restricted from stretching and filling properly. Cardiac troponin I （cTnI） mutation-caused myofibril Ca2＋ hypersensitivity has been shown to be associated with impaired diastolic function. This study aimed to investigate the linkage between the genotype and clinical therapy of RCM. Methods： Five sporadic pediatric RCM patients confirmed by echocardiography were enrolled in this study.Whole-exome sequencing （WES） was performed for the cohort to find out candidate causative gene variants. Sanger sequencing confirmed the WES-identified variants. Results： TNNI3 variants were found in all of the five patients. R192H mutation was shared in four patients while R204H mutation was found only in one patient. Structure investigation showed that the C terminus of TNNI3 was flexible and mutation on the C terminus was possible to cause the RCM. Catechins were prescribed for the five patients once genotype was confirmed. Ventricular diastolic function was improved in three patients during the follow-up. Conclusions： Our data demonstrated that TNNI3 mutation-induced RCM1 is the most common type of pediatric RCM in this study. In addition, WES is a reliable approach to identify likely pathogenic genes of RCM and might be useful for the guidance of clinical treatment scheme.展开更多
Background:The hereditary spastic paraplegias(HSPs)are a group of clinically and genetically heterogeneous disorders.Approximately 10% of the autosomal dominant(AD)HSPs(ADHSPs)have the spastic paraplegia 3A(SPG3A)geno...Background:The hereditary spastic paraplegias(HSPs)are a group of clinically and genetically heterogeneous disorders.Approximately 10% of the autosomal dominant(AD)HSPs(ADHSPs)have the spastic paraplegia 3A(SPG3A)genotype which is caused by ATL1 gene mutations.Currently there are more than 60 reported ATL1 gene mutations and the genotype-phenotype correlation remains unclear.The study aims to investigate the genotypephenotype correlation in SPG3A patients.Methods:We performed a reanalysis of the clinical features and genotype-phenotype correlations in 51 reported studies exhibiting an ATL1 gene mutation.Results:Most HSPs-SPG3A patients exhibited an early age at onset(AAO)of<10 years old,and showed an autosomal dominant pure spastic paraplegia.We found that 14% of the HSPs-SPG3A patients presented complicated phenotypes,with distal atrophy being the most common complicated symptom.The AAO of each mutation group was not statistically significant(P>0.05).The mutational spectrum associated with ATL1 gene mutation is wide,and most mutations are missense mutations,but do not involve the functional motif of ATL1 gene encoded atlastin-1 protein.Conclusions:Our findings indicate that there is no clear genotype-phenotype correlation in HSPs-SPG3A patients.We also find that exons 4,7,8 and 12 are mutation hotspots in ATL1 gene.展开更多
Tumor infiltrating lymphocytes (TIL) were cultured with “moxibustion serum”(MS), and the results were examined by flow cytometry. The results indicated that MS could enhance the proliferation of TIL,accelerate it to...Tumor infiltrating lymphocytes (TIL) were cultured with “moxibustion serum”(MS), and the results were examined by flow cytometry. The results indicated that MS could enhance the proliferation of TIL,accelerate it to reach the exponential growth phase, and assist recombinant interleukin 2 (rIL-2) to enhance successively the percentage of CD3^+ positive cells, maintain the number of CD4^+ positive T cells, promote greatly the percentage of CD8^+ positive T cells among TILs, and reverse the CD4^+/CD8^+ ratio. Such cooperative effects rely on relative specificity of acupoints. It is suggested that MS is beneficial to the growth of TIL both in the aspects of proliferation and phenotypes.展开更多
Objective： Hepatocellular carcinoma （HCC） is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, wh...Objective： Hepatocellular carcinoma （HCC） is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of micreRNA-718 （miR-718） in the malignant phenotype of HCC cells and its possible role in HCC diagnosis. Methods： Here we first used a methylthiazolyldiphenyl- tetrazolium bromide （MTT） assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein （GFP） reporter assay, Western blot, and quantitative real-time polymerase chain reaction （qRT-PCR） to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype. Results： We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 （EGR3） is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the via- bility and proliferation of HCC cells, and promot the migration and invasion of HCC cells. Conclusions： miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic 07） found that overexpreget for HCC.展开更多
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 nonsen
文摘Background： Restrictive cardiomyopathy （RCM） is the least common cardiomyopathy in which the walls are rigid and the heart is restricted from stretching and filling properly. Cardiac troponin I （cTnI） mutation-caused myofibril Ca2＋ hypersensitivity has been shown to be associated with impaired diastolic function. This study aimed to investigate the linkage between the genotype and clinical therapy of RCM. Methods： Five sporadic pediatric RCM patients confirmed by echocardiography were enrolled in this study.Whole-exome sequencing （WES） was performed for the cohort to find out candidate causative gene variants. Sanger sequencing confirmed the WES-identified variants. Results： TNNI3 variants were found in all of the five patients. R192H mutation was shared in four patients while R204H mutation was found only in one patient. Structure investigation showed that the C terminus of TNNI3 was flexible and mutation on the C terminus was possible to cause the RCM. Catechins were prescribed for the five patients once genotype was confirmed. Ventricular diastolic function was improved in three patients during the follow-up. Conclusions： Our data demonstrated that TNNI3 mutation-induced RCM1 is the most common type of pediatric RCM in this study. In addition, WES is a reliable approach to identify likely pathogenic genes of RCM and might be useful for the guidance of clinical treatment scheme.
基金This study was supported by the National Scientific Foundations of China(81000484)Natural Scientific Fundation of Zhejiang Province(LY17H090002)+2 种基金the Research Fundation of Zhejiang Health(2008QN017,2016144072)the Natural Science Foundation of Shandong Province(ZR2013HQ016)the Key Research and Development Project of Shandong Province(2015GGH318011).
文摘Background:The hereditary spastic paraplegias(HSPs)are a group of clinically and genetically heterogeneous disorders.Approximately 10% of the autosomal dominant(AD)HSPs(ADHSPs)have the spastic paraplegia 3A(SPG3A)genotype which is caused by ATL1 gene mutations.Currently there are more than 60 reported ATL1 gene mutations and the genotype-phenotype correlation remains unclear.The study aims to investigate the genotypephenotype correlation in SPG3A patients.Methods:We performed a reanalysis of the clinical features and genotype-phenotype correlations in 51 reported studies exhibiting an ATL1 gene mutation.Results:Most HSPs-SPG3A patients exhibited an early age at onset(AAO)of<10 years old,and showed an autosomal dominant pure spastic paraplegia.We found that 14% of the HSPs-SPG3A patients presented complicated phenotypes,with distal atrophy being the most common complicated symptom.The AAO of each mutation group was not statistically significant(P>0.05).The mutational spectrum associated with ATL1 gene mutation is wide,and most mutations are missense mutations,but do not involve the functional motif of ATL1 gene encoded atlastin-1 protein.Conclusions:Our findings indicate that there is no clear genotype-phenotype correlation in HSPs-SPG3A patients.We also find that exons 4,7,8 and 12 are mutation hotspots in ATL1 gene.
文摘Tumor infiltrating lymphocytes (TIL) were cultured with “moxibustion serum”(MS), and the results were examined by flow cytometry. The results indicated that MS could enhance the proliferation of TIL,accelerate it to reach the exponential growth phase, and assist recombinant interleukin 2 (rIL-2) to enhance successively the percentage of CD3^+ positive cells, maintain the number of CD4^+ positive T cells, promote greatly the percentage of CD8^+ positive T cells among TILs, and reverse the CD4^+/CD8^+ ratio. Such cooperative effects rely on relative specificity of acupoints. It is suggested that MS is beneficial to the growth of TIL both in the aspects of proliferation and phenotypes.
基金Project supported by the Science and Technology Project of Higher Education of Shandong Province(No.J12LK07),China
文摘Objective： Hepatocellular carcinoma （HCC） is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of micreRNA-718 （miR-718） in the malignant phenotype of HCC cells and its possible role in HCC diagnosis. Methods： Here we first used a methylthiazolyldiphenyl- tetrazolium bromide （MTT） assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein （GFP） reporter assay, Western blot, and quantitative real-time polymerase chain reaction （qRT-PCR） to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype. Results： We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 （EGR3） is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the via- bility and proliferation of HCC cells, and promot the migration and invasion of HCC cells. Conclusions： miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic 07） found that overexpreget for HCC.
