Research advances in the diagnosis and treatment of Pompe disease / 中国当代儿科杂志

Pompe disease, also called type II glycogen storage disease, is a rare autosomal recessive inherited disease caused by the storage of glycogen in lysosome due to acid α-glucosidase (GAA) deficiency, with the most severe conditions in the skeletal muscle, the myocardium, and the smooth muscle. Patients may have the manifestations of dyspnea and dyskinesia, with or without hypertrophic cardiomyopathy. GAA gene mutation has ethnic and regional differences, and new mutation sites are found with the advances in research. Gene analysis is the gold standard for the diagnosis of Pompe disease. Conventional methods, such as skin and muscle biopsies and dried blood spot test, have certain limitations for the diagnosis of this disease. In recent years, prenatal diagnosis and newborn screening play an important role in early diagnosis of this disease. Enzyme replacement therapy (ERT) has a satisfactory effect in the treatment of this disease, but it may lead to immune intolerance. New targeted gene therapy and modified ERT will be put into practice in the future. This article reviews the research advances in the diagnosis and treatment of Pompe disease.

Quantitative assessment of bladder neck compliance by using transvaginal real-time elastography of women.

To assess the feasibility of using ultrasound real-time elastography (RTE) to measure bladder neck compliance, we performed real-time elastography measurements by manually applying repetitive compression with the transducer on the scan position of the bladder neck. Instant elastography index (EI) and mean EI of anterior and posterior lips of the bladder neck were calculated. The EI values of anterior and posterior lips of the bladder neck were analyzed in relation to age, body surface area, body mass index, detrusor wall thickness and length, width and thickness of the bladder neck in healthy women. The intra-observer and inter-observer repeatability of measurements in different parts of the bladder neck were assessed using intra-class correlation coefficients with 95% confidence intervals and Bland-Altman analysis. There were no statistically significant differences between elastography measurements made by the same or two different observers in each area measured. There was no significant difference between anterior and posterior lip thickness of the bladder neck. The distribution of the elastography measurements indicated that the anterior lip of the bladder neck was slightly harder than the posterior lip. On the whole, from the results of the study, it was clear that EIs of the bladder neck were related to age in healthy women. Stepwise multiple regression analysis results revealed that age was the only independent factor modulating compliance of the bladder neck in healthy women. It is possible to provide a reproducible semi-quantification of real-time elastography in bladder neck compliance.

TLR4 mediates MAPK-STAT3 axis activation in bladder epithelial cells.

The role of Toll-like receptor 4 (TLR4) in immune cells is well characterized, but its biological properties in bladder epithelial cells (BECs), especially reciprocal crosstalk between mitogen-activated protein (MAP) kinase pathway and signal transducer and activator of transcription (STAT)3-mediated signal transduction elicited by TLR4 have not been demonstrated so far. The present studies were to demonstrate the signal transduction and inflammatory cytokine response elicited through activation of TLR4 in BECs with a special focus on the crosstalk between the MAPK-pathway and STAT3-mediated signals and its regulatory relevance for the inflammatory response towards lipopolysaccharide (LPS). We selected human bladder cancer T24 cell line in the present study and examined its expression of TLR4 by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. The expression of p38, extracellular signal regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and STAT3 were performed by RT-PCR, quantitative PCR, and Western blotting. Signal transduction was analyzed by Western blotting. Interleukin-6 (IL-6) and interleukin-10 (IL-10) secretion in culture supernatants were tested by human enzyme-linked immunosorbent assay (ELISA) kit. BECs of rat infection in vivo model and patients with cystitis glandularis (CG) were analyzed as described above. Our study demonstrated that TLR4 was significantly upregulated following LPS treatment, with the maximum mRNA expression occurring at 4 h after stimulation. Activation of TLR4 signaling by LPS resulted in phosphorylation of MAPK and STAT pathways and upregulation of IL-10 in dose- and time-dependent manners in T24 cells. Pretreatment of cells with SB203580 (inhibitor of p38) and SP600125 (inhibitor of JNK) attenuated LPS-induced IL-10 expression, whereas it markedly inhibited the STAT3 expression. IL-10 mRNA expression was increased in inflamed lesions compared to noninflamed tissue in rats and patients with CG disease. Our results demonstrate that activation of TLR4 signaling in BECs induces IL-10 expression via activation of p38 and JNK, and the activation of STAT-3 was upregulated. Our data indicated that the reciprocal crosstalk between the MAPK pathway and STAT3-mediated signal transduction forms a critical axis successively activated by LPS in BECs.

Diagnostic value of tumor marker pro-gastrin-releasing peptide in patients with small cell lung cancer: a systematic review / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lung cancer is one of the most common malignancies in the world and one of the leading cancers that result in death. The aim of this study was to evaluate and compare the diagnostic value of the serum tumor marker pro-gastrin-releasing peptide 31-98 (ProGRP31-98) to pathological diagnosis as reference standard in patients with suspected small cell lung cancer (SCLC).</p><p><b>METHODS</b>Literature searches covering 1978 through to 2009 were performed in Pubmed, OVID, MEDLINE, EMbase, Cancerlit, China National Knowledge Infrastructure (CNKI), and CBM using the key search words; 'small cell lung cancer', 'tumor marker', 'ProGRP31-98' and 'diagnostic tests', 'ELISA', 'EIA' and 'diagnostic accuracy'. Studies were collected and data analyzed to evaluate the diagnostic value of serum ProGRP31-98 levels for the diagnosis of SCLC compared with pathology. Eligibility criteria for inclusion in the analysis were based on criteria for diagnostic research published by the Cochrane Screening and Diagnostic Tests</p><p><b>METHODS</b>Group (SDTMG). The characteristics of the included articles were appraised and the data were extracted from the original articles for further statistical analysis of study heterogeneity using Review Manager 4.2 software. Based on study heterogeneity analysis, a suitable 'effect' model was selected to calculate pooled sensitivity and specificity by meta-analysis. A Summary Receiver Operating Characteristic (SROC) curve and the area under the curve (AUC) were generated and sensitivity analysis conducted.</p><p><b>RESULTS</b>A total of 22 articles were entered into this meta-review, including 11 English articles with a quality at level C. In total, the studies involved 6759 subjects, of which 1470 were diagnosed with SCLC by pathology, and 5289 subjects diagnosed with non-SCLC (NSCLC). The meta-analysis showed that heterogeneity among studies was high (P = 0.00001, I(2) = 86.8%). With ELISA, the pooled sensitivity was 0.72 (0.70 to 0.75 at 95%CI) and the pooled specificity was 0.93 (0.92 to 0.94 at 95%CI); the SROC and the AUC were 0.8817. These data suggest that ProGRP31-98 has a relatively high rate of missed diagnosis (28%), but a relatively low rate of misdiagnosis (7%).</p><p><b>CONCLUSION</b>From meta-analysis, we concluded that serum ProGRP31-98 is a valuable marker with a high specificity for diagnosis of SCLC with a similar diagnostic accuracy to pathology.</p>

Advances in echocardiography on cardiac resynchronization therapy in patients with heart failure / 中国医学科学院学报

Cardiac resynchronization therapy (CRT) has became an alternative treatment in patients with severe medically refractory heart failure in recent years. Several large studies have demonstrated the effectiveness of CRT, which can improve the atrioventricular, interventricular, and intraventricular dyssynchronies. Echocardiography can be used to evaluate cardiac mechanical synchrony by means of M-mode, pulse Doppler, tissue Doppler, 3D, and other techniques, and can therefore be used to screen patients, select lead location, optimize pacemaker parameters, and follow up patients who have undergone CRT. This article reviews the strength and shortcomings of some commonly used echocardiographic techniques when they are applied in patients with heart failure.

Effects of nuclear factor-?B on cell apoptosis and left ventricular segmental function in acute myocardial ischemia-reperfusion / 中华急诊医学杂志

Objective To probe the effects of nuclear factor kappa B (NF-?B) on cell apoptosis and left ventricular segmental function in acute ischemia repeffusion in dogs.Method Twenty-four dogs were randomly divided into three groups:without left anterior artery (lAD) ligation group (C group),LAD was occluded 30 min following reperfusion 120 minutes in isehemical reperfusion group (IR group),and dogs were administered with PDTC before LAD ligation in ischemical reperfusion plus pyorrole dithitocarbamate group (PDTC group).The left ventricular segmental function was detected by echo cardiography using strain rate anlysis software.EF measured by Simpson's method.Cardiac myocyte apoptosis numbers were determined by terminal deoxynudeotidy transferease-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL).lmmunohistochemistry and western-blot anylysis of NF-?B protein expression.Results NF-?B was obviously expression on injury myocardium of IR group,and increased significantly in contrast to control group (P0.05)Conclusions NF-?B might play an important role in acute myocardial ischemia reperfusion.PDTC reduces myocardial iscbemia/repeffasion injury by preventing expression of factor NF-?B.