Potential risk of hyperuricemia: leading cardiomyocyte hypertrophy by inducing autophagy.

BACKGROUND: Clinical studies have shown that hyperuricemia is associated with many cardiovascular diseases; however, the mechanisms involved remain unclear. In this study, we investigated the effect of uric acid on cardiomyocytes and the underlying mechanism. METHODS AND RESULTS: H9c2 cardiomyocytes were treated with various concentrations of uric acid. 3-Methyladenine (3-MA) or Compound C was added before treatment with uric acid. The expression of myocardial hypertrophy-related genes was measured using polymerase chain reaction (PCR). The cell surface area was calculated using ImageJ Software. Western blotting was used to measure the protein levels. Uric acid increased the gene expression of Nppa, Nppb, and Myh5, which are involved in myocardial hypertrophy, and the relative cell surface area of cardiomyocytes in a dose-dependent manner. Consistently, the ratio of LC3II/I, which is a biomarker of autophagy, increased dose-dependently, whereas the protein level of p62, a protein that is degraded by autophagy, decreased. 3-MA, an autophagy inhibitor, rescued uric acid-induced myocardial hypertrophy. Treatment with uric acid increased the level of phosphorylated adenosine monophosphate kinase (AMPK), as well as its downstream effector unc-51-like kinase (ULK1). Pharmacological inhibition of AMPK by Compound C attenuated the uric acid-induced activation of autophagy and myocardial hypertrophy. CONCLUSIONS: Uric acid induces myocardial hypertrophy by activating autophagy via the AMPK-ULK1 signaling pathway. Decreasing the serum uric acid level may therefore be clinically beneficial in alleviating cardiac hypertrophy.

Plasma microRNA-320, microRNA-let-7e and microRNA-21 as novel potential biomarkers for the detection of retinoblastoma.

Retinoblastoma (RB) is a childhood malignancy caused by inactivation of the RB gene, with neuron-specific enolase (NSE) levels considered as its diagnostic marker. MicroRNAs (miRNAs) have been proven to play a significant role in multiple physiological and pathological processes and several miRNAs were identified as tumor biomarkers in recent studies. In the present study, 65 plasma samples were collected from RB patients and 65 samples from healthy individuals to serve as controls. The miRNA levels were measured via quantitative reverse transcription-polymerase chain reaction and their association with RB was assessed by statistical data analysis and receiver operating characteristic curves. Plasma miRNA (miR)-320, miR-let-7e and miR-21 levels were downregulated in the patient samples, the areas under the curves (AUCs) were 0.548-0.660, whereas the AUCs of combined classifiers were ≥0.990. The plasma miRNA levels, particularly of miR-320, were found to be of value in RB diagnosis and may be considered as novel diagnostic biomarkers.

[Analysis on the safety of ophthalmic artery cannulation for intra-arterial chemotherapy in 42 patients with intraocular stage retinoblastoma].

OBJECTIVE: To investigate the safety of treatment with ophthalmic artery cannulation for intra-arterial chemotherapy (IAC) for children with intraocular retinoblastoma (RB). METHOD: In the RB Treatment Center of General Hospital of Armed Police Forces between January 2009 and September 2011, 42 patients who were diagnosed intraocular RB and treated with ophthalmic artery cannulation for IAC, 8 patients were treated 1 circle, 31 patients were treated 2 circles and 3 patients were treated 3 circles (total, 96 times). Each month had IAC once. The ophthalmic and the whole body evaluations were performed during IAC and after IAC for each circle, the blood cell count, alanine aminotransferase (ALT), serum creatinine (Scr), CK-MB content before and after IAC for 1 circle, 2 circles and 3 circles were determined. RESULT: (1) In 52 eyes of 42 patients, 44 eyes (84.6%) were in remission. (2) Successful IAC was achieved in all cases, no severe side effects occurred during IAC. (3) The main ophthalmic complications were eyelid edema and blepharoptosis after IAC, the incidence for 1 circle was 18% (2/11) and 9% (1/11); for 2 circles was 29% (11/38) and 21% (8/38); for 3 circles was all 100% (3/3). The rare complications were vitreous hemorrhage and heterotropia, the incidence was all 2% (1/42). The incidence of eyelid edema and blepharoptosis had no significant differences for 1 circle IAC compared with 2 circles (P > 0.05); the incidence of eyelid edema and blepharoptosis had significant differences for 3 circles IAC compared with 2 circles and 1 circle (P < 0.01). (4) No fever, septicemia and other systemic toxic effects occurred. (5) ALT of 19% patients (8/42) elevated temporarily and CK-MB of 24% patients (10/42) increased. The blood cell counts, ALT, Scr, and CK-MB content before IAC had no significant differences compared with that at 24 h after IAC for 1 circle, 2 circles and 3 circles (P > 0.05). CONCLUSION: Ophthalmic artery cannulation for IAC is a safe and effective method in treating intraocular stage retinoblastoma.

[114 children with acquired non-severe aplastic anemia benefitted from androgen].

This study was purposed to assess the efficacy of stanozolol for treatment of childhood patients with acquired non-severe aplastic anemia (NSAA). The records of 114 children with acquired NSAA treated in hospital between January 1996 and January 2009 were analyzed retrospectively. All patients received stanozolol with the dose of 0.1 mg/(kg·d). Some patients were treated with supportive care. The incidence and the risk factors of progression severe aplastic anemia (SAA) including gender, age, absolute neutrophil count, absolute reticulocyte count, dependent or independent of transfusion, the ratio of granulocytes and erythrocytes were evaluated. The results indicated that at a median follow-up of 52 months (range 5 - 181), 6 patients (5.3%) progressed into SAA, 93 (81.6%) remained in NSAA, and 15 (13.2%) had complete remission. Patients with dependent of transfusion (platelet count < 10 × 10(9)/L and/or haemoglobin < 70 g/L) have higher risk to progress into SAA (19.2% vs 1.1%) (p = 0.016); patients with lower absolute neutrophil count (ANC) (< 0.8 × 10(9)/L) or with lower absolute reticulocyte count (ARC) (< 40 × 10(9)/L) at diagnosis have higher risk to progress into SAA (8.1% vs 0%) (p = 0.029); (9.1% vs 1.7%) (p = 0.034); Those patients with lower ANC (ANC < 0.8 × 10(9)/L) and lower ARC (ARC < 40 × 10(9)/L) have higher risk into progress to SAA (19.2% vs 1.1%) (p = 0.016). It is concluded that NSAA patients treated with Stanozolol progress into SAA with the rate of 5.3%. Those patients with dependent of transfusion or ANC < 0.8 × 10(9)/L or/and ARC < 40 × 10(9)/L have higher risk of progress into SAA.

[Clinical utility of reticulocyte hemoglobin content for the diagnosis of iron deficiency anemia in children].

OBJECTIVE: To study the clinical utility of measuring reticulocyte hemoglobin content (CHr) in the diagnosis of iron deficiency anemia (IDA) in children. METHODS: One hundred children with IDA at ages of 1 to 6 years and 50 healthy children were enrolled. Red blood cell parameters, CHr, hemoglobin (Hb), red blood count (RBC) and mean corpusular volume (MCV), were determined using the Blood Cell Analyzer. Serum ferritin (SF) levels were determined using radioimmunoassay double antibody techique. Soluble serum transferrin (sTfR) levels were determined using ELISA. RESULTS: The values of Hb (100 ± 6 g/L vs 126 ± 8 g/L) and CHr (18 ± 5 pg vs 31 ± 3 pg) in the IDA group were significantly lower than normal controls (P<0.01). SF levels (11 ± 4 µg/L) in the IDA group were also lower than normal controls (59 ± 36 µg/L) (P<0.01). In contrast, the values of sTfR in the IDA group were significantly higher than normal controls (4.8 ± 2.1 mg/L vs 1.4 ± 0.6 mg/L; P<0.01). In both groups, there was a positive correlation between the values of CHr and Hb [r=0.540 (control group), r=0.734 (IDA group); P<0.01]. In the IDA group, CHr was positively correlated with SF(r=0.464; P<0.01) and negatively correlated with sTfR(r=-0.450; P<0.01). When the cut-off value of CHr was 27.8 pg, the sensitivity and specificity for the diagnosis of IDA were 88.0% and 90.0%, respectively and the area under the ROC curve was 0.948. CONCLUSIONS: CHr can be used as an index for the diagnosis of IDA in children.

[Pathogenesis of Fanconi anemia: FA-BRCA network -- review].

Fanconi anemia (FA) is a rare genetic disease with both autosomal and X-linked inheritance, characterized by genomic instability. The cells from individuals with FA are highly sensitive to DNA-crosslinking drugs, such as mitomycin C (MMC), diepoxybutane (DEB) and so on. Now at least 13 genes (FA-A, B, C, D1, D2, E, F, G, I, J, L, M, N) have been identified, whose products participate in a DNA damage-response network involving breast cancer susceptibility gene products, BRCA1 and BRCA2. The impaired DNA repair due to mutations in FA genes is thought to be one of the main pathogenesis of FA, also closely related to the development of some cancers. In this review, the advances of study about FA-BRCA network are summarized.