Protocatechuic acid promotes cell proliferation and reduces basal apoptosis in cultured neural stem cells

Protocatechuic acid (PCA), a phenolic compound isolated from the kernels of Alpinia oxyphylla, showed anti-oxidant neuroprotective property in our previous study. However, it is still unknown whether PCA have effects on the cultured neural stem cells (NSCs). In this study, we investigated the roles of PCA in the survival and apoptosis of rat NSCs under normal conditions. NSCs obtained from 13.5-day-old rat embryos were propagated as neurospheres and cultured under normal conditions with or without PCA for 4 and 7 days. The cell viability was determined by the cell counting kit-8 (CCK-8) test, while cell proliferation was assayed by bromodeoxyuridine (BrdU) labeling. PCA increased the cellular viability of NSCs and stimulated cell proliferation in a dose- and time-dependent manner. Apoptotic cells were detected after 4 days by observing the nuclear morphological changes and flow cytometric analysis. Compared with the control on both culture days, treatment with PCA effectively reduced the levels of apoptosis of NSCs. At the same time, the reactive oxygen species (ROS) level in NSCs was depressed. In addition, PCA also significantly decreased the activity of elevated caspase-3, indicating that PCA may inhibit apoptosis of NSCs via suppression of the caspase cascade. These results suggest that PCA may be a potential growth inducer and apoptosis inhibitor for NSCs.     

The role of an Ommaya reservoir in the management of children with cryptococcal meningitis

Cryptococcal meningitis is the most common life-threatening fungal infection and is associated with high mortality in children. Amphotericin B plus flucytosine and fluconazole is the optimal current therapy. Implantation of an Ommaya reservoir for intraventricular infusion of medication and aspiration of cerebrospinal fluid (CSF) for the treatment of increased intracranial pressure (ICP) has been reported. Intraventricular injection of amphotericin B through an Ommaya reservoir in children with cryptococcal meningitis has not been reported previously. We report two children who had cryptococcal meningitis and associated increased intracranial pressure, and were treated with an Ommaya reservoir. Both patients experienced rapid reversal of symptoms. At the time of discharge both patients had recovered and have remained asymptomatic.     

Genetic polymorphisms of glutathione S-transferase T1 and bladder cancer risk: a meta-analysis

In recent years, there have been numerous papers emphasizing the relationship between Glutathione S-transferases polymorphisms and bladder cancer risk, but the findings have not reached a consensus. The relationship between glutathione S-transferase T 1 null genotype and bladder cancer susceptibility is now even more disputable. Therefore, we present a meta-analysis of (nested) case–controlled, genotype-based studies (including 37 studies, 6,986 cases and 9,166 controls) examining this association. Using a fixed-effect model, statistically significant increase was observed between glutathione S-transferase T 1 deletion and bladder cancer risk for the overall studies (OR = 1.12; 95% confidence interval (CI): 1.04–1.21; P = 0.004 for Z test; I ² = 47.43 for heterogeneity). After adjusting the result using trim-and-fill method, the outcome still had significant difference with little downgrade (OR = 1.10, 95% CI = 1.02–1.18). Three potential sources of heterogeneity including ethnicity, source of control and smoking status were also assessed. Minor increased correlation was found only in population-based studies (OR = 1.16; 95% CI = 1.03–1.30; I ² = 47.16). Our analysis suggests that glutathione S-transferase T 1 null status is associated with a modest increase in the risk of bladder cancer and the difference exiting in source of control has been confirmed. Due to limited sample size, various confounding variables as well as discrepancy in study design, a valid conclusion still cannot be confirmed.     

Relation between soluble intercellular adhesion molecule-1, statin therapy, and long-term risk of clinical cardiovascular events in patients with previous acute coronary syndrome (from PROVE IT-TIMI 22)

High levels of adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1), are associated with long-term risk of cardiac events in patients with and without stable coronary artery disease. The relation between sICAM-1 and long-term risk after acute coronary syndromes (ACSs) and the influence of statin treatment has not been explored. Using a nested case-control design, patients with ACS who were enrolled in the PROVE IT-TIMI 22 trial were matched for age, gender, smoking, diabetes, type of ACS presentation, and revascularization for index event (583 patients with recurrent events vs 581 controls). Patients with recurrent events were identified as such by death, myocardial infarction, or hospitalization for recurrent ACS. Soluble ICAM-1 was measured at study entry (approximately 7 days after ACS). After adjusting for statin regimen and other risk factors, patients in quartiles 2 to 4 were at a higher risk of clinical events compared with those in quartile 1 (odds ratio 1.6 for quartile 4 vs 1, 95% confidence interval 1.1 to 2.3, p = 0.02). The risk of adverse events in patients with sICAM-1 levels in quartiles 2 to 4 was most marked in subjects who were allocated to standard dose statin therapy, even after adjusting for low-density lipoprotein cholesterol and C-reactive protein at day 30. The risk in quartiles 2 to 4 was somewhat attenuated in the intensive therapy group. In conclusion, in this large study of patients with ACS, we provide evidence that increased endothelial activation after ACS is independently associated with increased long-term risk of death, myocardial infarction, or recurrent ACS.     

Novel polymorphisms in the myosin light chain kinase gene confer risk for acute lung injury

The genetic basis of acute lung injury (ALI) is poorly understood. The myosin light chain kinase (MYLK) gene encodes the nonmuscle myosin light chain kinase isoform, a multifunctional protein involved in the inflammatory response (apoptosis, vascular permeability, leukocyte diapedesis). To examine MYLK as a novel candidate gene in sepsis-associated ALI, we sequenced exons, exon-intron boundaries, and 2 kb of 5' UTR of the MYLK, which revealed 51 single-nucleotide polymorphisms (SNPs). Potential association of 28 MYLK SNPs with sepsis-associated ALI were evaluated in a case-control sample of 288 European American subjects (EAs) with sepsis alone, subjects with sepsis-associated ALI, or healthy control subjects, and a sample population of 158 African American subjects (AAs) with sepsis and ALI. Significant single locus associations in EAs were observed between four MYLK SNPs and the sepsis phenotype (P<0.001), with an additional SNP associated with the ALI phenotype (P=0.03). A significant association of a single SNP (identical to the SNP identified in EAs) was observed in AAs with sepsis (P=0.002) and with ALI (P=0.01). Three sepsis risk-conferring haplotypes in EAs were defined downstream of start codon of smooth muscle MYLK isoform, a region containing putative regulatory elements (P<0.001). In contrast, multiple haplotypic analyses revealed an ALI-specific, risk-conferring haplotype at 5' of the MYLK gene in both European and African Americans and an additional 3' region haplotype only in African Americans. These data strongly implicate MYLK genetic variants to confer increased risk of sepsis and sepsis-associated ALI.     

血小板输注：预防出血的量效分析

本研究评价再生障碍性贫血患者使用血小板输注预防出血的有效剂量。将即将进行造血干细胞移植的血液肿瘤和实体肿瘤患者随机分组,当清晨血小板计数≤10000／mm^3时,给予低、中、高剂量血小板输注（按体表面积：1.1×10^11／mm^2,2．2×10^11／mm^2或4．4×10^11／mm^2）,评估每日出血情况。主要观察终点为2级或以上出血（WHO）。     

Diagnostic performance of contrast-enhanced ultrasound and enhanced magnetic resonance for breast nodules

In the current study, we sought to evaluate the diagnostic efficacies of conventional ultrasound (US), contrastenhanced US (CEUS), combined US and CEUS and magnetic resonance imaging (MRI) in detecting focal solid breast lesions. Totally 117 patients with 120 BI-RADS category 4A-5 breast lesions were evaluated by conventional US and CEUS, and MRI, respectively. SonoVue was used as contrast agent in CEUS and injected as an intravenous bolus; nodule scan was performed 4 minutes after bolus injection. A specific sonographic quantification software was used to obtain color-coded maps of perfusion parameters for the investigated lesion, namely the time-intensity curve. The pattern of contrast enhancement and related indexes regarding the time-intensity curve were used to describe the lesions, comparatively with pathological results. Histopathologic examination revealed 46 benign and 74 malignant lesions. Sensitivity, specificity, and accuracy of US in detecting malignant breast lesions were 90.14%, 95.92%, and 92.52%, respectively. Meanwhile, CE-MRI showed sensitivity, specificity, and accuracy of 88.73%, 95.92%, and 91.67%, respectively. The area under the ROC curve for combined US and CEUS in discriminating benign from malignant breast lesions was 0.936, while that of MRI was 0.923, with no significant difference between them, as well as among groups. The time-intensity curve of malignant hypervascular fibroadenoma and papillary lesions mostly showed a fast-in/fast-out pattern, with no good correlation between them (kappa < 0.20). In conclusion, the combined use of conventional US and CEUS displays good agreement with MRI in differentiating benign from malignant breast lesions.     

Characterization of hydrogels prepared from copolymerization of the different degrees of methacrylate-grafted chondroitin sulfate macromers and acrylic acid

Different degrees (between 20 and 75%) of methacrylate-grafted chondroitin sulfate (CS-MA) were synthesized. These CS-MA macromers were further copolymerized with acrylic acid (AA) at the molar ratio of 1 to 5 to form hydrogels. The sol percents of these CS-MA-AA hydrogels decreased and the cross-linking densities were studied with respect to the degrees of MA substitution onto CS-MA. The cytotoxicity with the increase in degree of MA substitution (DS) onto CS-MA as well as their hydrogels prepared from the corresponding macromers was tested using 293T cells. The cell viability of human dermal fibroblast and mescenchymal stem cells was further tested upon exposure to 75% CS-MA for 1-, 3-, and 7-day incubation period. The hydrogels maintained degradability for long periods of time as evidenced by SEM. A model protein, BSA, demonstrated the prolong-release behaviors of these hydrogels in simulated gastric fluids and pH 7.4 phosphate buffer solutions and a faster release rate in the presence of chondroitinase and esterase at pH 7.4.