Thrombocytosis and eosinophilia in 32 Chinese neonatal incontinentia pigmenti.

INTRODUCTION: Incontinentia pigmenti (IP) is a rare X-linked dominant genetic disease affecting ectodermal tissue and often misdiagnosed in the neonatal period. The aim of this study was to highlight sequential clinical features and evaluate prognosis of the 32 neonatal IP patients. MATERIAL AND METHODS: A retrospective descriptive analysis was performed, using the clinical, blood analytical, pathological, radiological, genetic, and followed-up data of neonatal patients diagnosed with IP from 2010 to 2021, in Xi'an, China. RESULTS: Of the 32 patients, two (6.25%) were male. Thirty babies (93.75%) had eosinophilia (eosinophilic granulocyte count: 0.31-19.9 × 109 , mean proportion of white blood cells: 20.98 ± 15.21%). Twenty babies (62.5%) had thrombocytosis (thrombocyte count: 139-975 × 109 , mean count: 416.76 ± 176.82). Thirty-one babies (96.88%) exhibited the first three cutaneous lesion stages characterized by erythema and superficial vesicles on inflammatory bases in a linear distribution in the first week of age. Thirteen babies (40%) combined nervous system abnormalities, and nine babies (28.13%) had retinopathy. Two types of genetic mutations were detected in the NEMO gene. Nineteen babies were followed up. According to the follow-up, four babies displayed psychomotor retardation, and five babies developed a decrease in vision with astigmatism and amblyopia. CONCLUSION: It is important that 30 babies (93.75%) had eosinophilia and 20 babies (62.5%) had thrombocytosis. Therefore, we speculate that the mechanism of the injury may be related to the platelet aggregation on the basis of the increase in eosinophil cells and the release of inflammatory factors.

Serum and glucocorticoid inducible kinase 1 modulates mitochondrial dysfunction and oxidative stress in doxorubicin-induced cardiomyocytes by regulating Hippo pathway via Neural precursor cell-expressed developmentally down-regulated 4 type 2.

Doxorubicin (Dox) was reported to cause mitochondrial dysfunction and oxidative stress in cardiomyocytes, leading to cardiomyocyte apoptosis and ultimately heart failure. Serum and glucocorticoid inducible kinase 1 (SGK1) participates in the progression of various cardiovascular diseases. Thus, we aimed to explore the role and regulatory mechanism of SGK1 in Dox-induced cardiomyocyte injury. The expression of SGK1 was evaluated in blood samples of heart failure children, and in myocardial tissues and blood samples of Dox-induced rats. Subsequently, we treated cardiomyocytes with Dox in vitro. A gain-of-function assay was performed to assess the effects of SGK1 on mitochondrial dysfunction and oxidative stress in Dox-induced cardiomyocytes. Furthermore, the modulation of SGK1 on Neural precursor cell-expressed developmentally down-regulated 4 type 2 (NEDD4-2) expression and the subsequent Hippo pathway was validated. In our study, we found that SGK1 was downregulated in blood samples of heart failure children, as well as myocardial tissues and blood samples of Dox-induced rats. SGK1 overexpression alleviated the decreases of mitochondrial complex activity, mitochondrial membrane potential, adenosine triphosphate (ATP) content and ATP synthetase activity stimulated by Dox. Besides, SGK1 overexpression reversed the promoting effects of Dox on oxidative stress and apoptosis. Mechanistically, SGK1 overexpression inhibited the expression of NEDD4-2 and blocked the subsequent activation of Hippo pathway. NEDD4-2 overexpression or activation of Hippo reversed the protective effects of SGK1 overexpression on Dox-induced cardiomyocyte injury. In conclusion, our results revealed that SGK1 modulated mitochondrial dysfunction and oxidative stress in Dox-induced cardiomyocytes by regulating Hippo pathway via NEDD4-2.

Clinical Characteristics of Anaphylaxis in Children Aged 0-16 Years in Xi'an, China.

INTRODUCTION: Anaphylaxis is a serious systemic hypersensitivity reaction that usually has a rapid onset and may cause death. The aim of this study was to clarify the clinical characteristics of anaphylaxis in children of all ages in Xi'an, China. METHODS: A retrospective study was conducted on anaphylaxis cases in the emergency department of the Affiliated Children's Hospital of Xi'an Jiaotong University between January 1, 2016, and July 1, 2021. The statistical methods used were the χ2 test, Fisher's exact test, and Z-test. RESULTS: A total of 110 cases of anaphylaxis were collected: 70% were male, 13 were <1 year old, 17 were 1-2 years old, 42 were 3-6 years old, 38 were 7-16 years old, 10 (9.1%) had ≥2 anaphylaxis, and 75 (68.1%) had a previous history of allergy. The triggers of anaphylaxis were analyzed: 50 cases (45.5%) were induced by food, 37 cases (33.6%) by drugs, 6 cases (5.5%) by insect bites, 4 cases (3.6%) by exercise, and 12 cases (11.8%) by unknown causes. Common food allergens were milk (20%, 10/50), buckwheat (16%, 8/50), eggs (14%, 7/50), and fruits (14%, 7/50). The most common drug triggers were antibiotics (59.4%, 22/37), non-steroidal anti-inflammatory drugs (NSAIDs) (10.8%, 4/37), vaccines (10.8%, 4/37), and herbal medicines (10.8%, 4/37). Common food allergens vary by age: milk and eggs for infants, fruit for children aged 1-2 years, and buckwheat for children older than 3 years. Ninety-eight cases (89.1%) had skin mucosal involvement, 78 (70.9%) had respiratory compromise, 45 (40.9%) had cardiovascular compromise, and 31 (28.2%) had gastrointestinal symptoms. Cardiovascular compromise and reduced level of consciousness were statistically different between the age groups (p < 0.05). Twenty cases (18.2%) had resolved spontaneously when they reached the hospital, 53 cases (48.1%) received epinephrine, 18 (16.4%) were hospitalized, and 2 (1.8%) experienced a biphasic reaction. CONCLUSIONS: Males are overrepresented in children with anaphylaxis, and food and drugs are common triggers in children. However, the types of common food triggers differ across age groups, and infants are more likely to have cardiovascular compromise and a reduced level of consciousness. However, the use of epinephrine remains inadequate. The training of clinical staff in recognizing anaphylaxis needs to be strengthened.

LincRNA RMRP Regulates Phenylephrine-induced Cardiomyocyte Hypertrophy by Means of Targeting miR-1.

ABSTRACT: Cardiac hypertrophy is a feature of hypertrophic cardiomyopathy (HCM), which could lead to heart failure and other cardiovascular diseases. Cardiomyocyte hypertrophy (CH) is the primary characteristic of cardiac hypertrophy. Long noncoding RNA (lncRNA, lincRNA) plays an important role in CH. In this study, the expression of linc-RMRP and its correlation with cardiac hypertrophy were analyzed in cardiac tissues of patients with HCM. Real-time qPCR and western blotting measured the expressions of lincf-RMRP, miR-1, and hypertrophic marker genes. RNA pulldown and luciferase reporter gene assays were performed to validate the combination between linc-RMRP and miR-1. We confirmed that Linc-RMRP was upregulated in both cardiac hypertrophy tissues and phenylephrine (PE)-induced CH cells, and the cells presented hypertrophic features, enlarged cell surface area and volume, elevated total protein contents, and increased expressions of ANP, BNP, ß-MHC, and activated p70S6K and 4EBP1. Bioinformatic analysis found that linc-RMRP directly bonds to miR-1. RNA pulldown, mutation, and luciferase reporter gene assays verified this combination. Silencing linc-RMRP significantly attenuated hypertrophic responses induced by PE while the expression of miR-1 was released. However, the transfection of miR-1 inhibitor reversed the effects of linc-RMRP knockdown exerted on PE-treated cardiomyocytes. In summary, our study identified the modulatory role linc-RMRP played in regulating PE-induced CH by means of binding miR-1, and this might provide a new target for cardiac hypertrophy therapy.

Absence of miR-223-3p ameliorates hypoxia-induced injury through repressing cardiomyocyte apoptosis and oxidative stress by targeting KLF15.

Apoptosis of cardiomyocytes and oxidant stress are considered essential processes in the progression of cardiovascular diseases. A hypoxic stress which causes apoptosis of cardiomyocytes is the main problem in ischemic heart disease. The aim of the present study was to explore the functional role and potential mechanisms of miR-223-3p in hypoxia-induced cardiomyocyte apoptosis and oxidative stress. Here, we observed a increment of miR-223-3p level accompanied by the decrease of Krüppel-like zinc-finger transcription factor 15 (KLF15) expression in response to hypoxia. Additionally, absence of miR-223-3p manifestly dampened hypoxia-induced cardiomyocyte injury in H9c2 cells, including improving cell viability, attenuating the LDH leakage and preventing cardiomyocyte apoptosis accompanied by an increase in the expression of Bcl-2 and a decrease in the expression of Bax and C-caspase 3 in the setting of hypoxia. Moreover, depletion of miR-223-3p evidently retarded oxidant stress by inhibiting reactive oxygen species generation and lipid peroxidation, as well as enhancing antioxidant enzyme activity in H9c2 cells following exposure to hypoxia. More importantly, KLF15 was a direct and functional target of miR-223-3p. Further data validated that miR-223-3p negatively regulated the expression of KLF15. Mechanistically, deletion of KLF15 partly abrogated the suppressive effects of miR-223-3p deletion on hypoxia-induced cardiomyocyte apoptosis and oxidative stress. Taken all data together, our findings established that our study defines a novel mechanism by which miR-223-3p protects against cardiomyocyte apoptosis and oxidative stress by targeting KLF15, suggesting that the miR-223-3p/KLF15 may be a potential therapeutic target for ischemic heart conditions.

[Expression and significance of interleukin-6, interferon-inducible protein-10 and interleukin-17 in serum and synovial fluid of patients with juvenile idiopathic arthritis].

OBJECTIVE: To detect the disparity of three cytokines interleukin-6 (IL-6), interferon-inducible protein 10 (IP-10) and interleukin-17 (IL-17) in peripheral blood (PB) and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA). METHOD: Serum concentrations of the three cytokines were measured in 27 patients with 13 systemic-onset JIA (sJIA), 14 polyarticular JIA (pJIA) and 28 healthy controls using enzyme-linked immunosorbent assay (ELISA). Nineteen patients with no marked arthritis symptom or only temporary arthralgia were enrolled in probable sJIA group. SF from 18 patients with 7 sJIA, 11 pJIA were examined for cytokine levels. RESULT: (1) The statistically significant difference in serum IL-6 was detected between sJIA and healthy control group [28.0(4.2-59.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P < 0.05], but no significant difference between probable sJIA and healthy control group [11.8(7.7-39.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P > 0.05] was found. There were statistically significant differences between sJIA group and healthy control group in serum concentrations of IL-17 [14.0(9.8-34.3) ng/L vs. 9.8 (7.9-16.2) ng/L, P < 0.05], yet compared to healthy control group, no significant difference in concentration level of IL-17 was found in pJIA Group [14.2(9.9-16.9) ng/L vs. 9.8(7.9-16.2) ng/L, P > 0.05].(2) In sJIA and pJIA SF, the median IP-10 level was significantly higher compared to respective PB levels [619.7 (160.9, 873.1) ng/L vs. 64.8 (27.4-111.9) ng/L;660.9 (401.9, 1349.8) ng/L vs. 97.4 (41.9-222.1) ng/L, P < 0.01, respectively], but there was only significant difference in IL-17 between pJIA SF and PB [22.9 (17.1, 45.8) ng/L vs. 14.2 (9.9-16.9) ng/L, P < 0.01]. CONCLUSION: IL-6 may play more important role in the pathogenesis of sJIA. Moreover, IL-6 may be the biomarker associated with arthritis in early JIA stage. Both autoinflammation and autoimmune response may be involved in the pathogenesis of sJIA. IL-17 enrichment may only occur in local joint, the levels of IL-17 in PB may not be significantly increased. The prominent expression gradient between SF and PB of IP-10 maybe the basis of performing chemotaxis and further causing joint damage.