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Biomedical subjects

Chaur-Jong Hu

Publications and source records attributed to Chaur-Jong Hu.

At least 19 recordsLinked to original sources

Segmental study of the median nerve versus comparative tests in the diagnosis of mild carpal tunnel syndrome.

OBJECTIVE: The aims of this study were to analyze normative data of nerve conduction studies (NCS) by optimal transformations, and compare the utility of electrodiagnostic tests in detecting mild carpal tunnel syndrome (CTS). METHODS: In 131 hands of patients with mild CTS and 136 hands of controls, the segmental study of the median nerve between the digit-palm and palm-wrist segments, and the median-to-ulnar and median-to-radial comparative tests were performed. Normal limits were derived by calculating the mean+/-2 standard deviations of the optimally transformed data of the controls. The specificity, sensitivity, and misclassification rate were calculated to evaluate the utility of each test. RESULTS: All tests had high specificities, ranging from 98.5 to 100%. The distoproximal latency ratio (DPLR) of the median nerve showed the highest sensitivity and the difference between the median and radial sensory latencies (D1M-D1R) the second highest, but there was no statistical difference between them. The difference between the median and ulnar mixed nerve latencies in the palm-to-wrist segment (PM-PU) showed the lowest sensitivity. Misclassification rates of the DPLR, D1M-D1R, and PM-PU were 6.9, 3.8, and 6.1%, respectively. CONCLUSIONS: Optimal transformation of NCS data is mandatory to diminish the effect of skewness and enhance the diagnostic accuracy. As compared to the comparative tests, the segmental study of the median nerve is more easily applied and yields higher sensitivity in detecting mild CTS. SIGNIFICANCE: With a high diagnostic yield and easy application, the segmental study of the median nerve may routinely be used to evaluate patients with mild CTS.

Adult↗

Promoter region methylation and reduced expression of thrombospondin-1 after oxygen-glucose deprivation in murine cerebral endothelial cells.

Angiogenesis is induced in response to ischemia. Thrombospondin-1 (TSP-1) is a potent angiostatic factor. Silencing of TSP-1 expression may contribute to the postischemic angiogenesis. Upregulation of TSP-1, in contrast, may terminate the postischemic angiogenesis. A possible mechanism that silences TSP-1 expression is the DNA methylation of its promoter region. DNA methylation has been reported following cerebral ischemia. The present study aimed to explore whether methylation of the promoter region of TSP-1 regulates its expression after oxygen-glucose deprivation (OGD) in murine cerebral endothelial cells (CECs) in vitro. Sublethal OGD increased the extent of methylation of the promoter region of TSP-1 with a concurrent decrease in TSP-1 mRNA and protein expression in CECs. After reoxygenation, demethylation of the TSP-1 promoter region led to the restoration of TSP-1 mRNA and protein expression. The extent of methylation of the promoter region of TSP-1 was inversely correlated with the extent of TSP-1 gene expression at mRNA and protein levels after OGD. Oxygen-glucose deprivation-induced reduction in the TSP-1 mRNA level was not accompanied by a change in mRNA stability. These findings raise the possibility that OGD downregulation of TSP-1 expression is at least in part due to methylation of its promoter region.

Animals↗

A novel compound heterozygous mutation of K494_V495 deletion plus R496L and D487_F489 deletion in extreme C-terminus of cytochrome P450c17 causes 17alpha-hydroxylase deficiency.

17alpha-Hydroxylase deficiency is a rare disease caused by mutation of the CYP17 gene, resulting in hypertension, hypokalemia, female sexual infantilism or male pseudohermaphroditism, low blood cortisol and low plasma renin activity. Herein, we report a female Taiwanese with 17alpha-hydroxylase deficiency. The CYP17 genes of this patient and five members of her family were analyzed by PCR-direct sequencing. One allele of the patient contains a 9-bp (c. 1459-1467 GACTCTTTC: D487, S488, F489) deletion, which is prevalent in Southeast Asia. The other allele has a 6-bp (c. 1480-1485 AAGGTG: K494, V495) deletion and an R496L (c. 1487 G>T) missense mutation, which is a novel mutation. Site-directed mutagenesis, in vitro expression and functional analysis in HEK-293T cells showed that this novel mutation [K494_V495 Del; R496L] resulted in complete loss of 17alpha-hydroxylase and 17,20-lyase activity. Thus this novel mutation in the extreme C-terminus abolishes enzyme activity, and when accompanied by a 9-bp deletion at codons 487-489 in the other allele, results in 17alpha-hydroxylase/17,20-lyase deficiency in this patient.

Adrenal Hyperplasia, Congenital↗

Proteomic identification of lower apolipoprotein A-I in Alzheimer's disease.

Many researches have been trying to find the potential biomarkers for Alzheimer's disease (AD). We hereby used the proteomics method to search for protein expression differences in the serum between AD patients and controls. We enrolled 59 AD patients and 74 age- and sex-matched controls in this study. Ten AD patients and 10 controls were selected for proteomic analysis. Apolipoprotein A-I (ApoA-I) was found to have a lower expression in the AD group by a proteomics two-dimensional gel electrophoresis study. We further measured the serum ApoA-I level which was significantly lower in the AD patients (112.29 +/- 21.33 mg/dl) in comparison to the controls (144.53 +/- 19.91 mg/dl; p < 0.0002). Lower serum ApoA-I levels might be a potential biomarker for AD.

Aged↗

The genetic studies of dementias in Taiwan.

In Taiwan, Alzheimer's disease (AD) followed by vascular dementia (VsD) is the most common cause of dementia among Taiwanese (ethnic Chinese). Several studies have documented the increase of risk for AD among the apolipoprotein E gene allele 4 (ApoE4) carriers in Taiwanese. It is a consensus that ApoE4 is the most important risk factor for AD at present. The researchers also found that ApoE4 allele frequency is lower in Taiwanese, around 7%, than it in the most Caucasian populations. This phenomenon raises the hypothesis that low ApoE4 allele frequency contributes to low prevalence of AD in Taiwanese. Besides, many genetic studies were involved in genetic impacts on modulation or regulation of the manifestation, progression, and treatment response of AD. But, these genetic studies are still inconclusive. Few familial AD attributed to PS1 gene mutation has been identified. The genetic studies of VsD are just beginning and NOTCH3 gene mutation has been detected in Taiwanese cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) families. Since there is a large proportion of non- ApoE4-associated AD in Taiwanese, it remains more researches to look for novel genetic factors in Taiwanese. Based on the Japanese experience of studies, the association between the polymorphisms of ApoE and familial AD, sporadic early-onset AD respectively warrants further investigation.

Alzheimer Disease↗

Genetic characteristics of dementia in Taiwan.

The most common causes of dementia in Taiwan are Alzheimer's disease (AD) followed by vascular dementia (VaD). Several genetic studies have documented an increased risk of AD among apolipoprotein E gene allele 4 (ApoE4) carriers in Taiwanese (ethnic Chinese). Although ApoE4 is considered the most important risk factor for AD, the ApoE4 allele frequency is lower in Taiwanese (around 7%), than that in most Caucasian populations (over 10%). This phenomenon raises the hypothesis that low ApoE4 allele frequency contributes to the low prevalence of AD in Taiwanese. Other studies of the genetic impacts on modulation or regulation of manifestations, progression, and treatment response of AD in Taiwan have been inconclusive. Familial AD, which is conferred by PS1 gene mutation has been identified. There were very few studies of fronto-temporal dementia (FTD) or dementia with Lewy body (DLB) in Taiwan. Genetic studies of VaD remain limited and only NOTCH3 gene mutation has been detected in a Taiwanese cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) family. Limited data indicated that non- ApoE4-associated AD may represent a larger proportion of AD in Taiwanese, suggesting the existence of novel genetic factors which remain to be identified.

Alzheimer Disease↗

Natural resistance-associated macrophage protein 1 gene polymorphisms in rheumatoid arthritis.

OBJECTIVES: To investigate the association of natural resistance-associated macrophage protein 1 gene (NRAMP1) polymorphisms with rheumatoid arthritis (RA) in Taiwan. METHODS: NRAMP1 polymorphisms were determined from 113 RA patients and 74 healthy controls using the polymerase chain reaction/restriction fragment length polymorphism method. RESULTS: The genotype frequencies of NRAMP1 823 C/C, 1703G/G (543D/D), and 1729+55 del 4 TGTG+/+ (244/244) were significantly higher in patients with RA than in controls. Similar findings were also evident in allele frequencies and allele carriage frequencies of 823C, 1703G (543D), and 1729+55 del 4 TGTG+ (244). The associations of these polymorphisms with RA were independent of HLA-DR4. Linkage disequilibria could be found between 823C and 1703G, and between 1703G and 1729+55 del 4 TGTG+. The estimated haplotype frequency of NRAMP1 823C/1703G/1729+55 del 4 TGTG+ was significantly increased in RA patients compared with controls. We also found that patients with 823 C/C had a significantly lower prevalence of rheumatoid nodule than those without 823 C/C. CONCLUSION: NRAMP1 823C, 1703G (543D), and 1729+55 del 4 TGTG+ (244) are precipitating factors for the development of RA in Taiwan. The estimated NRAMP1 823C/1703G/1729+del 4 TGTG+ haplotype is associated with susceptibility to RA. NRAMP1 823 C/C prevents the development of rheumatoid nodule in RA patients.

Alleles↗

Toll-like receptor 4 gene C119A but not Asp299Gly polymorphism is associated with ischemic stroke among ethnic Chinese in Taiwan.

Stroke is one of the leading causes of death in the world. Most stroke patients are classified as having ischemic stroke. The causes of ischemic stroke are very diverse. Atherosclerosis resulting in cerebral or carotid arterial stenosis/occlusion plays the most important role in the occurrence of ischemic stroke. Inflammatory processes or immune responses are involved in the formation of atherosclerosis. Toll-like receptor 4 (TLR4) is a member of the toll-like receptor (TLR) family. TLRs are pattern-recognition receptors, which initiate innate immune responses after interaction with pattern-specific ligands. A polymorphism of the TLR4 gene, Asp299Gly, is associated with an increased risk for coronary heart diseases in Caucasian populations. In this study, we explored the complete coding regions of TLR4 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Single-strand conformation polymorphism (SSCP), and sequencing and found obvious ethnic differences. There was no Asp299Gly polymorphism among the ethnic Chinese examined in this study. We found only one polymorphism on intron 1 (A119C) among our samples. The allele frequencies of 119A were 0.0256 and 0.0022 among the patients and controls, respectively. The odds ratio of 119A of TLR4 in ischemic stroke was 11.71 (95% CI: 1.52-90.01). This polymorphism was significantly associated with ischemic stroke. These data possibly implicate TLR4 as an important genetic factor for stroke in ethnic Chinese populations despite the rarity of the Asp299Gly polymorphism.

Aged↗

Pravastatin attenuates ceramide-induced cytotoxicity in mouse cerebral endothelial cells with HIF-1 activation and VEGF upregulation.

Ceramide is a pro-apoptotic lipid messenger that induces oxidative stress and may mediate apoptosis in cerebral endothelial cells (CECs) induced by TNF-alpha/cycloheximide, lipopolysaccharide, oxidized LDL, IL-1, and amyloid peptide. Exposure of CECs to C2 ceramide for 12 h caused cell death in a concentration-dependent manner, with a LC50 of 30 microM. Statins are inhibitors of 3-hydroxyl-3-methyl coenzyme A reductase which is the rate-limiting enzyme for cholesterol biosynthesis. Pretreatment with pravastatin at 20 microM for 16 h substantially attenuated ceramide cytotoxicity in mouse CECs. Increases in vascular endothelial growth factor (VEGF) expression were detected within 1-3 h after pravastatin treatment. This pravastatin action was accompanied by the activation of hypoxia-inducible factor-1 (HIF-1), a transcription factor known to activate VEGF expression. These results raise the possibility that pravastatin may protect CECs against ceramide-induced death via the HIF-VEGF cascade.

Animals↗

Relationship between vertebral bone marrow blood perfusion and common carotid intima-media thickness in aging adults.

PURPOSE: To evaluate the relationship between vertebral marrow blood perfusion and common carotid intima-media thickness (IMT) in aging adults. MATERIALS AND METHODS: An age- and sex-matched case control study was conducted. Subjects were contacted and enrolled voluntarily according to a database containing 2,258 cases that received carotid ultrasonography examination at our hospital in the previous two years. Forty-three pairs of subjects (56 male, 30 female; aged 44-85 years, average 63 years) underwent dynamic contrast-enhanced magnetic resonance (MR) study of the lumbar spine. The average peak enhancement percentage of the second to fourth lumbar vertebrae was used to represent the vertebral marrow perfusion status for each subject. The common carotid IMT, presence of plaque, peak enhancement percentage, body mass index (BMI), systolic and diastolic blood pressure, serum total cholesterol, high-density lipoprotein (HDL), and triglycerol levels were acquired for statistical analysis. RESULTS: The average peak enhancement percentage was significantly lower in thickened IMT group compared to the normal IMT group (73 +/- 23 vs. 90 +/- 27, P=0.0023). The carotid IMT inversely correlated with vertebral peak enhancement percentage (r=-0.33, P=0.0018). The vertebral peak enhancement percentage was significantly lower in subjects with presence of any carotid plaque (P=0.032). Common carotid IMT was the only significant variable that was negatively associated with vertebral marrow perfusion after adjusting for the effect of sex, age, blood pressure, BMI, total cholesterol, HDL, and triglycerol level in linear regression model (P=0.008). CONCLUSION: Our data demonstrate the negative association between vertebral marrow blood perfusion and common carotid IMT. These results suggest that common carotid IMT may provide the information of tissue perfusion status of the vertebral bone marrow.

Adult↗

Aspirin inhibits monocyte chemoattractant protein-1 and interleukin-8 expression in TNF-alpha stimulated human umbilical vein endothelial cells.

Atherosclerosis and its complications such as stroke, myocardial infraction and peripheral vascular disease, remain the major causes of morbidity and mortality in the world. Studies have showed that chemokines and adhesion molecules are involved in causing atherosclerosis by promoting directed migration of inflammatory cells. Monocyte chemoattractant protein-1 (MCP-1) is one of the key factors critical for the initiating and developing of atherosclerotic lesions. IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Aspirin is the most common drug used to prevent the complications of atherosclerosis such as stroke and coronary heart disease. In this study, we found that aspirin inhibited TNF-alpha (10 ng/ml)-induced MCP-1 and IL-8 expression at the RNA and protein levels in human umbilical vein endothelial cells (HUVECs), monocyte adhesion and transmigration, and that its inhibitory effects were not due to decreased HUVEC viability as assessed by MTT test. Aspirin at the dose as low as 10 microg/ml significantly inhibited the release of TNF-stimulated MCP-1 by 29.1% (P = 0.008) and IL-8 by 26.9% (P = 0.0146) as compared to TNF-stimulated release. Antibodies pretreatment were likely to decrease the production of MCP-1 (P < 0.0001) and IL-8 (P < 0.0001). Furthermore, aspirin (10 microg/ml) inhibited U937 cell adhesion by a 13.4% (P = 0.0119) inhibition as compared to TNF-stimulated alone. Finally, at higher concentration, aspirin also inhibited U937 migration to HUVEC by 89.1% (P = 0.0475) as compared to TNF-stimulated alone. These results in our study suggest that aspirin inhibits TNF-alpha stimulated MCP-1 and IL-8 release in HUVECs, for its additional therapeutic effects of aspirin in causing atherosclerosis.

Animals↗

DAT polymorphism and diverse clinical manifestations in methamphetamine abusers.

The clinical outcome for methamphetamine (MAP) abusers is variable. MAP exerts its biological activity through rapid conversion to amphetamine (AP) and MAP itself. The dopamine transporter (DAT) is the main modulator of MAP/AP-induced dopamine release and dopamine neurotoxicity, and is also the major regulator of dopamine level in the brain. We tested for an association between a DAT-gene polymorphism and clinical variations in MAP abusers. A total of 146 MAP abusers were enrolled in the study and classified into three clinically distinct groups: MAP dependence (n = 30), MAP psychosis (n = 88) and chronic MAP psychosis (n = 28). Patients with schizophrenia (n = 79) and healthy controls (n = 72) were also recruited for the study. The 40 base pair variable number tandem repeat polymorphism in the 3'-untranslated region of the DAT was the focus of the investigation. The subjects were all Chinese residents of Taiwan. The respective allelic frequencies for DAT repeats 11, 10 and 9 were 0.067, 0.833 and 0.083 for the MAP-dependence group, 0.006, 0.864 and 0.119 for the MAP psychosis group, 0.018, 0.893 and 0.089 for the chronic MAP psychosis group, 0.019, 0.911 and 0.07 for the schizophrenic controls, and 0.021, 0.889 and 0.083 for the healthy controls. No significant associations were demonstrated between this DAT polymorphism in genotype and allele frequency and the clinical outcome of MAP abusers. The biological relevance of the variable number tandem repeat polymorphism in the 3'-untranslated region of DAT in MAP abusers was not demonstrated in this study.

3' Untranslated Regions↗

Cytochrome P450 1A1 and manganese superoxide dismutase gene polymorphisms in Behçet's disease.

OBJECTIVE: To investigate the association of cytochrome p450 1A1 (CYP1A1) and manganese superoxide dismutase (MnSOD) gene polymorphisms with susceptibility to Behçet's disease (BD) in Taiwan. METHODS: The polymorphisms of CYP1A1 and MnSOD genes were determined in 51 patients with BD and 91 healthy controls by polymerase chain reaction/restriction fragment length polymorphism methods. RESULTS: The frequencies of CYP1A1 4889G and 4887A were significantly increased in patients with BD. In contrast, there was no significant difference in the frequencies of MnSOD gene polymorphisms between patients with BD and controls. Linkage disequilibrium was found between CYP1A1 4889G and CYP1A1 6235C in controls and patients with BD. However, a similar finding could not be found between CYP1A1 4889G and 4887A. We also found that the association of CYP1A1 4889G with BD was dependent on the presence of CYP1A1 4887A. On the other hand, the association of CYP1A1 4887A with BD was dependent on the presence of CYP1A1 4889G. An additive effect of CYP1A1 4889G and 4887A on the susceptibility to BD could be found. CONCLUSION: Simultaneous presence of CYP1A1 4889G and 4887A is associated with development of BD in Taiwan.

Adult↗

Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in reactive arthritis.

To investigate the role of cytochrome P450 1A1 (CYP1A1) and manganese superoxide dismutase (Mn SOD) genes polymorphisms in the susceptibility to reactive arthritis, the polymorphisms of CYP1A1 and Mn SOD genes were determined in 43 patients with reactive arthritis following Chlamydia trachomatis infection and 92 healthy controls by polymerase chain reaction (PCR)/restriction fragment length polymorphisms (RFLP) method. The frequencies of CYP1A1 4887C/A and C/A+A/A were significantly higher in patients with reactive arthritis than in controls. Moreover, the increased frequency of CYP1A1 4887A in patients with reactive arthritis is independent of HLA-B27. The frequency of Mn SOD 1183T/T tended to be increased in patients with reactive arthritis. We also found that the frequency of CYP1A1 4887A was significantly increased in Mn SOD 1183T/T(+) reactive arthritis patients compared with 1183T/T(+) controls. CYP1A1 4887A may be a risk factor for the development of reactive arthritis, especially in the presence of Mn SOD 1183T/T.

Arthritis, Reactive↗

Cytochrome P450 and manganese superoxide dismutase genes polymorphisms in systemic lupus erythematosus.

OBJECTIVES: To investigate the role of cytochrome P450 1A1 (CYP1A1) and manganese superoxide dismutase (Mn SOD) genes polymorphisms in the pathogenesis of systemic lupus erythematosus (SLE) in Taiwan. METHODS: CYP1A1 and Mn SOD genes polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism (RFLP) method in 90 patients with SLE and 94 healthy controls. RESULTS: The genotype frequency of CYP1A1 4887C/A was significantly higher in patients with SLE than in controls. The allele and phenotype frequencies of CYP1A1 4887A were also significantly increased in SLE patients. In contrast, there were no significant differences in the genotype, allele and phenotype frequencies of Mn SOD C1183T polymorphisms between patients with SLE and controls. We also found that SLE patients with CYP1A1 4887A had a trend of increasing prevalence of renal involvement, while Mn SOD C1183T polymorphisms were not associated with the renal involvement in SLE. CONCLUSIONS: CYP1A1 4887A may be a precipitating factor for the development of SLE. It also tended to be associated with the occurrence of renal involvement in SLE patients. A synergistic effect was found between CYP1A1 4887C/A and Mn SOD 1183T/T on the susceptibility to SLE.

Adult↗

Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in ankylosing spondylitis.

OBJECTIVES: To investigate the associations of cytochrome p450 1A1 (CYP1A1) and manganese superoxide dismutase (MnSOD) genes polymorphisms with the susceptibility to AS in Taiwan. METHODS: The polymorphisms of CYP1A1 and MnSOD genes were determined in 70 patients with ankylosing spondylitis (AS) and 93 healthy controls by polymerase chain reaction (PCR)/restriction fragment length polymorphisms (RFLP) methods. RESULTS: The genotype frequency of CYP1A1 4887C/A was significantly lower in patients with AS than in controls. The phenotype frequency of CYP1A1 4887A also tended to be decreased in patients with AS. There were no significant differences in the genotype, allele, and phenotype frequencies of MnSOD gene polymorphisms between patients with AS and controls. CONCLUSION: CYP1A1 4887A may be a protective factor for the development of AS in Taiwan. However, MnSOD gene polymorphisms are not associated with the susceptibility to AS.

Cytochrome P-450 CYP1A1↗

The association of beta-site APP cleaving enzyme (BACE) C786G polymorphism with Alzheimer's disease.

The deposition of amyloid beta-peptide (Abeta) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Beta-site APP cleaving enzyme (BACE) is the rate-limiting enzyme in the Abeta formation. BACE mutations/polymorphisms may be associated with AD. We searched the BACE coding region mutations/polymorphisms of cDNA in 25 AD patients and 100 healthy controls by single-strand conformational polymorphism. A polymorphism at BACE coding region was identified and confirmed to be 786C/G polymorphism by nucleotide sequencing. Based on these findings, we investigated the association of this polymorphism with the occurrence of AD by PCR-RFLP. A total of 98 AD patients along with 138 controls were recruited in the present study. The allele frequencies of the 786C/G polymorphism were 0.622 for C and 0.378 for G in AD. In controls, the C and G allele frequencies were 0.691 and 0.309, respectively. No significant association of this polymorphism with the occurrence of AD can be established. Larger sample size may be necessary to identify other potential mutations/polymorphisms among BACE gene.

Aged↗

Manganese superoxide dismutase and cytochrome P450 1A1 genes polymorphisms in rheumatoid arthritis in Taiwan.

To investigate the role of manganese superoxide dismutase (MnSOD) and cytochrome P450 1A1 (CYP1A1) gene polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan, MnSOD and CYP1A1 genes polymorphisms were determined by he polymerase chain reaction/restriction fragment length polymorphism method in 112 patients with RA and 96 controls. There were no significant differences in the genotype, allele, and phenotype frequencies of MnSOD Ala-9Val (C1183T) polymorphisms between patients with RA and controls. The polymorphism of MnSOD 5777T, threonine at the 58th amino acid, cannot be found in RA patients and controls in Taiwan. The allele and phenotype frequencies of CYP1A1 4887A and genotype frequency of CYP1A1 4887C/A were lower in RA patients than in controls, whereas the significant difference was lost after correction. MnSOD C1183T polymorphisms were not associated with the clinical manifestations of RA. However, RA patients with CYP1A1 4889G/G have significantly higher frequency of Sjögren's syndrome, especially in the presence of MnSOD 1183T/T. Patients with CYP1A1 4887C/A also have a trend to develop Sjögren's syndrome in the presence of MnSOD 1183T/T. The linkage disequilibrium between CYP1A1 4889G and CYP1A1 6235C can be found in this study. MnSOD gene polymorphisms are not related to susceptibility to RA in Taiwan, whereas individuals with CYP1A1 4887A tend to avoid the development of RA. Moreover, CYP1A1 4889G/G and 4887C/A may play a role in the development of Sjögren's syndrome, especially in the presence of MnSOD 1183T/T. These findings are preliminary. A further confirmation study is necessary.

Arthritis, Rheumatoid↗