Scutellarin activates IDH1 to exert antitumor effects in hepatocellular carcinoma progression.

Isochlorate dehydrogenase 1 (IDH1) is an important metabolic enzyme for the production of α-ketoglutarate (α-KG), which has antitumor effects and is considered to have potential antitumor effects. The activation of IDH1 as a pathway for the development of anticancer drugs has not been attempted. We demonstrated that IDH1 can limit glycolysis in hepatocellular carcinoma (HCC) cells to activate the tumor immune microenvironment. In addition, through proteomic microarray analysis, we identified a natural small molecule, scutellarin (Scu), which activates IDH1 and inhibits the growth of HCC cells. By selectively modifying Cys297, Scu promotes IDH1 active dimer formation and increases α-KG production, leading to ubiquitination and degradation of HIF1a. The loss of HIF1a further leads to the inhibition of glycolysis in HCC cells. The activation of IDH1 by Scu can significantly increase the level of α-KG in tumor tissue, downregulate the HIF1a signaling pathway, and activate the tumor immune microenvironment in vivo. This study demonstrated the inhibitory effect of IDH1-α-KG-HIF1a on the growth of HCC cells and evaluated the inhibitory effect of Scu, the first IDH1 small molecule agonist, which provides a reference for cancer immunotherapy involving activated IDH1.

Development of youth tennis players: A study based on the ranking history of top ATP/WTA players worldwide and China.

BACKGROUND: The top 100 ATP/WTA ranking points are a crucial indicator of entry into the high-level world of tennis players, and the number of players from a nation in this ranking reflects the overall level of their tennis. However, the growth time series characteristics of elite tennis athletes are unclear. OBJECTIVE: This study aims to examine the historical career ranking changes of elite players and provide valuable insights for aspiring young players looking to achieve success in the sport. At the same time, it is of great significance for the efficient and sustainable cultivation of Chinese tennis players. METHODS: Data on the rankings of 202 players were analyzed, Spearman and Pearson correlations were employed to investigate the association between ranking and time-use patterns. The variance test was utilized to compare disparities in time characteristics of the ranking, with a statistical significance level of p<0.05. RESULTS: There was a significant correlation between the time of entering the professional tournament ranking system and the ranking, top 100 time, top 100 age, and age of starting tennis. Top 50 ATP players are earlier than those ranked 51-100. There was a significant difference between the age of starting tennis and the time to top 10 among the ATP and WTA players. Chinese female players showed no significant differences compared to their global Top 10 counterparts in terms of time-to-success characteristics. CONCLUSION: The elite tennis players who achieve success typically start playing and competing in the sport at a young age, with professional competition often commencing around 18 years of age. Notably, these players frequently attain high rankings before reaching the age of 20. Furthermore, top 10 ATP male players tend to start tennis at an earlier age and require a shorter time to achieve a top 10 ranking compared with WTA female players.

Janus kinase inhibitor, tofacitinib, in refractory juvenile dermatomyositis: a retrospective multi-central study in China.

OBJECTIVES: Juvenile dermatomyositis (JDM) is a chronic autoimmune disease. Some patients remain in an active state even though they were administrated with a combination of corticosteroid and methotrexate. Existing research has suggested that interferon and Janus kinase played an important role in pathogenesis. Existing research has suggested the efficacy of JAK inhibitors (JAKi). Our retrospective study aimed to investigate the efficacy of tofacitinib in refractory JDM patients. METHODS: A total of eighty-eight patients in China who had been diagnosed with JDM and subjected to tofacitinib therapy for over 3 months were retrospectively analyzed. Skin and muscle manifestations were assessed using the Cutaneous Assessment Tool-binary method (CAT-BM), Childhood Myositis Assessment Scale (CMAS), and kinase. Pulmonary function was assessed using a high-resolution CT (computerized tomography) scan and pulmonary symptoms. All patients were subjected to regular follow-up, and core measures were assessed every 3 months after initiation. Furthermore, the data were analyzed using the Wilcoxon single test, Mann-Whitney U test, and chi-square test. RESULTS: Compared with the baseline data, skin and muscle manifestations were found significantly improved during the respective follow-up visit. At the most recent follow-up, nearly 50% of patients achieved a clinical complete response and six patients received tofacitinib monotherapy. Sixty percent of patients suffering from interstitial lung disease well recovered on high-resolution CT. Seventy-five percent of patients showed a reduction in the size or number of calcinosis, and 25% of patients showed completely resolved calcinosis. CONCLUSION: In this study, the result suggested that tofacitinib therapy exerted a certain effect on skin manifestations, muscle manifestations, interstitial lung disease (ILD), calcinosis, as well as downgrade of medication. In-depth research should be conducted to focus on the correlation between the pathogenesis of JDM and JAKi.

MiR-34a targets SIRT1 to reduce p53 deacetylation and promote sevoflurane inhalation anesthesia-induced neuronal autophagy and apoptosis in neonatal mice.

This study is to investigate the function of miR-34a and interactions between miR-34a, SIRT1, and p53 in sevoflurane-induced neuronal apoptosis and autophagy in neonatal mice. A mouse model was established by inhalation anesthesia with sevoflurane and injected with genetic reagents, followed by tests of learning and memory abilities and histological staining of the hippocampus. CCK-8 and AnnexinV/PI staining respectively measured the survival and apoptosis rates of primary hippocampal neurons cultured with sevoflurane. The expression levels of miR-34a, SIRT1, p53, Ac-p53, and autophagy- or apoptosis-related proteins were measured. Sevoflurane impaired the learning and memory abilities of mice, increased TUNEL-positive cells in their hippocampus, and hindered the survival of hippocampal neurons. Sevoflurane increased miR-34a, Bax, cleaved caspase-3, and the ratio of LC3-II/LC3-I and reduced SIRT1 and p62. MiR-34a overexpression promoted sevoflurane-induced neural damage, whereas SIRT1 inhibition or p53 upregulation counteracted the neuroprotection of miR-34a knockdown. SIRT1 was a target of miR-34a and promoted p53 deacetylation. MiR-34a promotes sevoflurane-stimulated neuronal apoptosis and autophagy in neonatal mice by inhibiting SIRT1 expression and subsequent p53 deacetylation.

A systematic review and meta-analysis of environmental factors associated with juvenile idiopathic arthritis.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanisms and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA. METHODS: MEDLINE (Ovid), EMBASE (Ovid), Cumulative Index of Nursing and Related Health Literature (EBSCOhost), science network (WOS, Clarivate Analytics), Chinese National Knowledge Infrastructure, and Chinese Biological Medical Database were systematically searched. Study quality was rated using the Newcastle-Ottawa Scale. Pooled estimates for each environmental factor were generated using a random-effects, inverse-variance method, where possible. The remaining environmental factors were synthesized in narrative form. RESULTS: This review includes environmental factors from 23 studies (6 cohorts and 17 case-control studies). Cesarean section delivery was associated with increased JIA risk (pooled relative risk [RR] 1.103, 95% CI 1.033-1.177). Conversely, maternal smoking of more than 20 cigarettes/day (pooled RR 0.650, 95% CI 0.431-0.981) and gestational smoking (pooled RR0.634, 95% CI 0.452-0.890) were associated with decreased JIA risk. CONCLUSION: This review identifies several environmental factors associated with JIA and demonstrates the huge breadth of environmental research. We also highlight the challenges of combining data collected over this period due to limited study comparability, evolution in healthcare and social practices, and changing environment, which warrant consideration when planning future studies.

Paraneoplastic pemphigus misdiagnosed as juvenile dermatomyositis: A case report.

Paraneoplastic pemphigus (PNP) is a rare autoimmune skin disease closely related to tumors, characterized by a maculopapular rash with mucosal pain, bronchiole occlusion, and respiratory failure may occur over time, even resulting in death. We report a rare case of a child with autoimmune PNP misdiagnosed as juvenile dermatomyositis (JDM), and summarize the key points of differentiation of clinical manifestations and auxiliary examinations of PNP and JDM. When the diagnosis is not clear because the patient has features not typical of JDM, then skin biopsy and other diagnostic studies should be considered prior to any immunosuppressive therapy, as this could potentially obscure and delay the diagnosis of malignancy.

Early onset is an indication of the severity of DADA2 disease.

OBJECTIVE: To find indicators of disease severity and factors of early remission in patients with deficiency of adenosine deaminase 2 (DADA2). METHODS: We enrolled six DADA2 patients from six families. Direct sequencing of adenosine deaminase 2 gene (ADA2) was performed by Sanger analysis. A literature review was conducted for articles regarding paediatric DADA2. RESULTS: We found that more organs were involved in early-onset (≤1 year of age) than in late-onset (>1 year of age) DADA2 patients had high level inflammatory responses, such as elevated ESR, SF, serum amyloid A and CRP. Disease severity was not significantly different from missense and frameshift mutation. Early administration of TNF inhibitor might result in better remission and reduce recurrence. In the literature, four articles describing 51 paediatric DADA2 patients were identified. We also found that fever, stroke, peripheral nervous system involvement, hypogammaglobulinaemia and hypertension were more frequent in early onset DADA2 patients. CONCLUSION: Early-onset DADA2 may be more severe. Early administration of TNF inhibitor can effectively reduce recurrence and quickly alleviate the disease.

The potential of plant extracts in cell therapy.

Cell therapy is the frontier technology of biotechnology innovation and the most promising method for the treatment of refractory diseases such as tumours. However, cell therapy has disadvantages, such as toxicity and poor therapeutic effects. Plant extracts are natural, widely available, and contain active small molecule ingredients that are widely used in the treatment of various diseases. By studying the effect of plant extracts on cell therapy, active plant extracts that have positive significance in cell therapy can be discovered, and certain contributions to solving the current problems of attenuation and adjuvant therapy in cell therapy can be made. Therefore, this article reviews the currently reported effects of plant extracts in stem cell therapy and immune cell therapy, especially the effects of plant extracts on the proliferation and differentiation of mesenchymal stem cells and nerve stem cells and the potential role of plant extracts in chimeric antigen receptor T-cell immunotherapy (CAR-T) and T-cell receptor modified T-cell immunotherapy (TCR-T), in the hope of encouraging further research and clinical application of plant extracts in cell therapy.

Chip-DSF: A rapid screening strategy for drug protein targets.

Identification of the drug target of lead compounds is an important means for rapid and efficient drug discovery. Protein chips are a high-throughput protein function analysis technology that has been widely used in screening drug protein targets in recent years. However, the verification of the results after high-throughput protein chip screening is still cumbersome. Based on our mature protein chip preparation platform, we prepared a protein chip containing 150 important high-frequency protein targets and used antibodies to prove the availability of the protein chip. To improve the accuracy of target screening, we combined the label-free differential scanning fluorimetry (DSF) with the protein chip, proposing the Chip-DSF strategy. Subsequently, we tested the method with small molecular ginsenoside-Rg2 (Rg2). The Chip-DSF strategy was used to successfully screen the potential target protein KRAS(G12C) of Rg2. Consistently, we found that Rg2 could inhibit NCI-H23 cell proliferation by inducing cell cycle arrest. Also, we found that Rg2 could reduce the amount of KRAS protein and inhibit the phosphorylation of KRAS downstream key signaling protein ERK1, RPS6, and P70S6K in NCI-H23 cells. Collectively, our Chip-DSF strategy could achieve rapid target verification which improved the accuracy and efficiency of target screening of protein chips.

Effect of sigh in lateral position on postoperative atelectasis in adults assessed by lung ultrasound: a randomized, controlled trial.

BACKGROUND: Postoperative atelectasis occurs in 90% of patients receiving general anesthesia. Recruitment maneuvers (RMs) are not always effective and frequently associated with barotrauma and hemodynamic instability. It is reported that many natural physiological behaviors interrupted under general anesthesia could prevent atelectasis and restore lung aeration. This study aimed to find out whether a combined physiological recruitment maneuver (CPRM), sigh in lateral position, could reduce postoperative atelectasis using lung ultrasound (LUS). METHODS: We conducted a prospective, randomized, controlled trial in adults with open abdominal surgery under general anesthesia lasting for 2 h or longer. Subjects were randomly allocated to either control group (C-group) or CPRM-group and received volume-controlled ventilation with the same ventilator settings. Patients in CPRM group was ventilated in sequential lateral position, with the addition of periodic sighs to recruit the lung. LUS scores, dynamic compliance (Cdyn), the partial pressure of arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2) ratio (PaO2/FiO2), and other explanatory variables were acquired from each patient before and after recruitment. RESULTS: Seventy patients were included in the analysis. Before recruitment, there was no significant difference in LUS scores, Cdyn and PaO2/FiO2 between CPRM-group and C-group. After recruitment, LUS scores in CPRM-group decreased significantly compared with C-group (6.00 [5.00, 7.00] vs. 8.00 [7.00, 9.00], p = 4.463e-11 < 0.05), while PaO2/FiO2 and Cdyn in CPRM-group increased significantly compared with C-group respectively (377.92 (93.73) vs. 309.19 (92.98), p = 0.008 < 0.05, and 52.00 [47.00, 60.00] vs. 47.70 [41.00, 59.50], p = 6.325e-07 < 0.05). No hemodynamic instability, detectable barotrauma or position-related complications were encountered. CONCLUSIONS: Sigh in lateral position can effectively reduce postoperative atelectasis even without causing severe side effects. Further large-scale studies are necessary to evaluate it's long-term effects on pulmonary complications and hospital length of stay. TRIAL REGISTRATION: ChiCTR1900024379 . Registered 8 July 2019,.

Identification of PDCD2 as a Candidate Target of Andrographolide That Arrests the Tumor Cell Cycle by Human Proteome-Scale Screening.

Andrographolide (andro) and its derivatives have been reported to have antitumor activity by arresting the cell cycle. However, the more precise mechanism has been controversial. Here, a proteome chip was used to screen drug targets in cells, and we discovered that andro can bind to PDCD2 (PD2), which has been shown to be associated with the cell cycle and mRNA nuclear export. Then, RNA-binding protein immunoprecipitation for PD2 was used to detect the quantity of cell cycle-related mRNAs, and the nuclear distribution difference analyses of these mRNAs in tumor cells after andro intervention, followed by systematic experiments, were performed to assess the downstream effects of this event in vivo and in vitro. Thus, the target spectrum of andro was revealed at the level of the human proteome chip for the first time, and this work demonstrated that andro, through targeting PD2, blocks the nuclear output of CDK mRNAs in the nucleus of tumor cells, further reduces the expression of cell CDK proteins, and finally causes tumor cell cycle arrest in phenotype and tumor tissue growth arrest in vivo.

Machine learning for screening and predicting the risk of anti-MDA5 antibody in juvenile dermatomyositis children.

Objective: The anti-MDA5 (anti-melanoma differentiation associated gene 5) antibody is often associated with a poor prognosis in juvenile dermatomyositis (JDM) patients. In many developing countries, there is limited ability to access myositis- specific antibodies due to financial and technological issues, especially in remote regions. This study was performed to develop a prediction model for screening anti-MDA5 antibodies in JDM patients with commonly available clinical findings. Methods: A cross-sectional study was undertaken with 152 patients enrolled from the inpatient wards of Beijing Children's Hospital between June 2018 and September 2021. Stepwise logistic regression, least absolute shrinkage and selection operator (LASSO) regression, and the random forest (RF) method were used to fit the model. Model discrimination, calibration, and decision curve analysis were performed for validation. Results: The final prediction model included eight clinical variables (gender, fever, alopecia, periungual telangiectasia, digital ulcer, interstitial lung disease, arthritis/arthralgia, and Gottron sign) and four auxiliary results (WBC, CK, CKMB, and ALB). An anti-MDA5 antibody risk probability-predictive nomogram was established with an AUC of 0.975 predicted by the random forest algorithm. The model was internally validated by Harrell's concordance index (0.904), the Brier score (0.052), and a 500 bootstrapped satisfactory calibration curve. According to the net benefit and predicted probability thresholds of decision curve analysis, the established model showed a significantly higher net benefit than the traditional logistic regression model. Conclusion: We developed a prediction model using routine clinical assessments to screen for JDM patients likely to be anti-MDA5 positive. This new tool may effectively predict the detection of anti-MDA5 in these patients using a non-invasive and efficient way.

l-Cysteine-Modified Graphene Oxide-Based Membrane for Chiral Selective Separation.

A novel chiral separation membrane was fabricated by assembling l-cysteine (l-Cys)-modified graphene oxide sheets. l-Cys modification leads to an enantiomer separation membrane with an accessible interlayer spacing of 8 Å, which allows high solvent permeability. In the racemate separation experiments under isobaric conditions, the enantiomeric excess (ee) values of alanine (Ala), threonine (Thr), tyrosine (Tyr), and penicillamine (Pen) racemates in the permeation solution were 43.60, 44.11, 27.43, and 46.44%, respectively. In the racemate separation experiments under negative pressure, the separation performances of Ala, Thr, and Tyr were still maintained, and the enantiomeric excess (ee) values of the filtrate after separation were 56.80, 54.57, and 32.34%, respectively. These results indicate that the as-prepared GO-Cys membrane has a great practical value in the field of enantiomer separation.

Xanthoceras sorbifolium Bunge: A Review on Botany, Phytochemistry, Pharmacology, and Applications.

Xanthoceras sorbifolium Bunge (Sapindaceae) is a native Chinese plant with promising applications as a biofuel feedstock and a source of novel drugs. Historical records and documents from different periods have mentioned the use of X. sorbifolium and its botanical constituents in treating diseases, highlighting its central role in Chinese and Mongolian traditional medicinal therapies. Phytochemical research has focused on the husks, leaves, trunks, and branches of this herb. A total of 278 chemical compounds have been isolated and divided into 8 categories: triterpenoids, flavonoids, phenylpropanoids, steroids, phenols, fatty acids, alkaloids, and quinones. Modern pharmacological studies on X. sorbifolium have demonstrated positive effects on learning and memory, as well as anti-inflammatory, anti-tumor, and anti-oxidative properties. This review provides a comprehensive analysis of the available research on X. sorbifolium, focusing on the relationship between chemical constituents, traditional uses, and pharmacological effects. We also assess the potential for therapeutic and other applications of this plant in support of further research and development of X. sorbifolium.

Long-term Outcomes of Patients with Systemic Lupus Erythematosus: A Multicenter Cohort Study from CSTAR Registry.

Objective: To study the long-term outcomes, in the context of both mortality and organ damage in patients with systemic lupus erythematosus (SLE) in the Chinese SLE Treatment and Research group (CSTAR) registry cohort. Methods: Patients were enrolled from April 2009 to February 2010 and they were followed up. The demographic data, clinical manifestations, labs test results and imaging examinations, disease activity (SLEDAI-2K), damage scores (SLLIC/Damage Index [SDI]), and medications were collected. Data were censored at either the last clinic visit or telephonic interview. Survival rate was analyzed by Kaplan-Meier (KM) method. COX proportional hazard model was adopted to perform the analysis of predicting factors for mortality and organ damage. Logistic regression analysis was employed to discuss the relationship among mortality, organ damage, and flare. Results: A total of 2104 patients were recruited at baseline and 1494 patients were followed up. The cumulative 1-year, 3-year, and 5-year survival rates were 98.3%, 96.9%, and 95.7%, respectively. Seventy-eight patients died during follow-up, and the main causes of death were infection (34.6%), active disease (26.9%), cardiovascular and cerebrovascular events (5.13%), and malignancy (5.13%). At entry, 247 patients presented with irreversible organ damage and it increased to 398 patients at the endpoint. The major accumulated organ damages were kidney (25.9%), musculoskeletal disease (20.2%), neuropsychiatric disease (12.2%), and pulmonary damage (10.9%). Cox regression analysis further showed that male, late disease onset, delayed diagnosis (diagnosis from disease onset >1 year), baseline organ damage, and specific organ involvements predicted for higher mortality. In addition, early disease onset was a protecting factor for organ damage, and anti-SSA was an independent predicting factor for new organ damage. Logistic regression analysis showed that flare predicted for more organ damage. Conclusion: The 5-year survival rate of Chinese SLE patients has improved and is comparable to Caucasians SLE patients. Disease flare impact on prognosis is the increasing risk of damage development. Early diagnosis, prevention for flare and damage to maintain remission, may improve outcome.

Modulating the antioxidant system by exogenous 2-(3,4-dichlorophenoxy) triethylamine in maize seedlings exposed to polyethylene glycol-simulated drought stress.

Maize (Zea mays L.), an important agricultural crop, suffers from drought stress frequently during its growth period, thus leading to a decline in yield. 2-(3,4-Dichlorophenoxy) triethylamine (DCPTA) regulates many aspects of plant development; however, its effects on crop stress tolerance are poorly understood. We pre-treated maize seedlings by adding DCPTA to a hydroponic solution and then subjected the seedlings to a drought condition [15% polyethylene glycol (PEG)-6000 treatment]. The activities of superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), and glutathione reductase (GR) were enhanced under drought stress and further enhanced by the DCPTA application. The activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and catalase (CAT) declined continuously under drought stress; however, the activities partially recovered with DCPTA application. Up-regulation of the activities and transcript levels of APX, GR, MDHAR and DHAR in the DCPTA treatments contributed to the increases in ascorbate (AsA) and glutathione (GSH) levels and inhibited the increased generation rate of superoxide anion radicals (O2·-), the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA), and the electrolyte leakage (EL) induced by drought. These results suggest that the enhanced antioxidant capacity induced by DCPTA application may represent an efficient mechanism for increasing the drought stress tolerance of maize seedlings.

Gene mutations and clinical phenotypes in 15 Chinese children with cryopyrin-associated periodic syndrome (CAPS).

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: c1789A

Development and Initial Validation of the Macrophage Activation Syndrome/Primary Hemophagocytic Lymphohistiocytosis Score, a Diagnostic Tool that Differentiates Primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome.

OBJECTIVE: To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. STUDY DESIGN: The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. RESULTS: Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from <1% for a score of <11 to >99% for a score of ≥123. A cutoff value of ≥60 revealed the best performance in discriminating pHLH from MAS. CONCLUSION: The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.

Gene mutations and clinical phenotypes in Chinese children with Blau syndrome.

The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified 10 missense mutations, out of which five were new: R334L, E383D, R471C, C495R and D512F. The rest of them, R334W, R334Q, G481D, M513T and R587C, have been reported previously. Among all the mutations, R334W, R334Q and C495R 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.