Identification of common differential genes in three animal models of diabetic nephropathy / 医学研究生学报

ObjectiveAnimal model is an important means to study the pathogenesis and drug therapy of diabetic nephropathy. In this paper, the techniques of bioinformatics were used to analyze the common susceptibility genes and pathways in the kidneys of three diabetic nephropathy animal models of BKS db/db, BKS eNOS-/db/db and DBA-STZ3, so as to discover new and important genes and pathways, thus providing new ideas for the study of the pathogenesis of diabetic nephropathy.MethodsThe GSE33744 dataset was downloaded from the GEO database, and the differential genes of three animal models of diabetic nephropathy were analyzed by Limma package in R language. The genes differentially expressed in all models were obtained by intersection, and were then analyzed by GO, KEGG and PPI networks and screened for key genes and pathways.Results144 genes were differentially expressed in three animal models of diabetic nephropathy. GO analysis showed that these genes were enriched in the cell membrane and extracellular regions; in biological processes such as innate immune response, oxidation-reduction process and immune system process; and in molecular functions such as oxidoreductase activity, carbohydrate binding and heme binding. KEGG analysis indicated that the differential genes were enriched in signaling pathways such as PPAR signaling pathway, arachidonic acid metabolism, butyric acid metabolism and circadian rhythm. PPI network analysis suggested that Cd68, Ccl6, Fcer1g, Tyrobp, Clec4n, Lyz2, Ms4a6d, Ly86, Ctss, Cfp and Mpeg1 may be the key genes in the development of diabetic nephropathy.ConclusionSome genes and signaling pathways are altered in multiple kidneys of the diabetic animal models, suggesting that these genes and pathways play an important role in the pathogenesis of diabetic nephropathy.

Effect of quercetin on doxorubicin-induced expression of MDR1 gene in HL-60 cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>Leukemia cells can acquire a multidrug resistant (MDR) phenotype in response to a wide variety of chemotherapeutic agents including doxorubicin (Dox). In addition to the constitutive expression in the leukemia prior to chemotherapy, a complex phenotype of pleiotropic resistance is presented in the residual or recurrent leukemia. Recent studies showed Dox-induced coexpression of COX2 and MDR1 genes in human leukaemia cells, and whether Dox-induced MDR1 up-regulation in acute leukaemia cells is dependent on COX2-transcriptional activity and thus might be overcome or prevented with COX2-promotor inhibitor quercetin interfering with COX2 expression and activity. This study was purposed to investigate the impacts of quercetin on Dox-induced mRNA expression of MDR1 and COX2 genes in HL-60 leukemia cells.</p><p><b>METHODS</b>The MDR1 and COX2 mRNA expression in HL-60 cells was detected by RT-PCR; the prostaglandin E2 (PGE2) release was measured by ELISA; the cytotoxicity of Dox was determined by MTT test.</p><p><b>RESULTS</b>The incubation of HL-60 cells with Dox not only up-regulated MDR1 mRNA, but also COX2 mRNA expression, and after co-incubation with quercetin or celecoxib, Dox-induced overexpression of MDR1 and COX2 mRNA were reduced by quercetin, not by celecoxib, whereas PGE2 release was significantly decreased with subsequent enhancement of Dox cytotoxic efficacy by both of them.</p><p><b>CONCLUSIONS</b>Dox-induced MDR1 up-regulation may be dependent on COX2-transcriptional activity, not PGE2, suggesting that the existence of causal link between COX2 and MDR1 expression induced by Dox, and modulation of COX2 transcriptional expression by quercetin would not only sensitize leukemia cells to Dox, but also prevent the acquisition of MDR during chemotherapy.</p>

Risk factors for invasive pulmonary fungal infection in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To analyze the risk factors for invasive pulmonary fungal infection (IPFI) and to provide a theoretical basis for the early prevention and treatment of IPFI.</p><p><b>METHODS</b>A retrospective case-control study was conducted on the clinical data of children hospitalized in the pediatric intensive care unit between January 2012 and March 2013. These children consisted of 48 patients with a clinical diagnosis of IPFI (IPFI group) and 106 pneumonia patients without a clinical diagnosis of IPFI (non-IPFI group). The clinical date of the two groups were compared and analyzed. The main risk factors for the development of IPIF were identified by unconditional multivariate logistic regression analysis.</p><p><b>RESULTS</b>Compared with the non-IPIF group, the IPIF group had significantly lower mean age and serum albumin level (P<0.01), significantly longer mean length of hospital stay, duration of antibiotic use, and duration of corticosteroid use (P<0.01), and significantly higher rates of malnutrition, invasive mechanical ventilation, indwelling catheter use, oropharyngeal fungal infection, and diarrhea (P<0.05). Multivariate logistic regression analysis showed that invasive mechanical ventilation, diarrhea, long duration of corticosteroid use, long duration of antibiotic use, young age, and low serum albumin level were independent risk factors for the development of IPFI.</p><p><b>CONCLUSIONS</b>For the infants with suspected IPFI for whom pathogenic examination is difficult to perform, IPFI should be considered in cases of invasive mechanical ventilation, diarrhea, long-time uses of broad-spectrum antibiotics and corticosteroids and hypoalbuminemia, and empirical antifungal therapy should be performed as soon as possible.</p>

Association study of a functional SNP rs28493229 of ITPKC gene and Kawasaki disease in a Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Kawasaki disease (KD) is a form of acute multi-systemic vasculitis with unknown etiology. It is the leading cause of acquired heart disease in children due to the frequent occurrence of coronary artery lesions (CALs). Recently, a C allele of rs28493229 (G/C) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene was found to significantly increase the risk for KD/CALs in Japanese population. It is important to confirm such finding in Chinese population to enable prognosis and personalized therapy for KD.</p><p><b>METHODS</b>A case-control study was performed. The patient group has included 206 unrelated patients with KD, and the control group included 285 age, gender and ethnically matched children who never had KD. Genotyping of rs28493229 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The allele, genotype and C allele carrier frequencies were compared between the two groups, patients with or without CALs, and patients who were resistant or responsive to (intravenous immunoglobulin, IVIG) treatment.</p><p><b>RESULTS</b>Frequency of the C allele of rs28493229 was significantly lower in both groups than that in the Japanese population (P< 0.01). No significant difference was detected between the two groups in terms of allele, genotype and C carrier of rs28493229 frequencies. Such frequencies were also similar between patients with or without CALs, resistant or responsive to IVIG treatment.</p><p><b>CONCLUSION</b>Our study has failed to prove any association between rs28493229 and KD/CALs in Chinese patients, which indicated that the C allele of rs28493229 may not be used as a molecular marker for determining KD susceptibility, prognosis and effect of treatment. The much lower frequency of C allele does not support its significance in the occurrence of KD/CALs in Chinese population. It is still necessary to find functional SNPs in ITPKC gene which is associated with KD/CALs in Chinese population.</p>

Clinical and immunological studies on neonatal infectious pneumonia / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore etiology, clinical manifestation and immunological changes of infectious pneumonia of neonates in Chengdu area.</p><p><b>METHODS</b>Serum specimens were collected from 111 infants with infectious pneumonia. Eight viral and mycoplasmal specific serum IgM antibodies were detected by enzyme linked immunosorbent assay (ELISA); C reactive protein (CRP), total IgG and its subclasses, IgA and IgM were determined by rate scattered nephelometry; T lymphocyte subpopulations were detected by biotin-streptavidin-peroxidase method, and clinical and other laboratory data were analyzed.</p><p><b>RESULTS</b>(1) Etiological agents: specific serum IgM antibodies were positive in 40 of 111 cases (36.0%) with pneumonias. All the 30 control infants were negative for the specific serum IgM antibodies. Among 111 infants with infectious pneumonia, 20.7% had single viral or mycoplasmal infection, 40.5% had bacterial infection, 15.3% had viral and mycoplasmal infection with bacterial infection; 23.4% had infection with unknown agents. (2) The most common clinical manifestations were tachypnea and cyanosis. The next were cough, milk choking, rales, retractions of the supraclavicular, intercostal and subcostal areas. Roentgenographic examination commonly revealed vague opacities, increased density and patchy infiltration. (3) Immune status: (1) CD(3), CD(4) cell counts of infants with pneumonias were lower than those of the controls while their serum IgA, IgM concentrations were higher than those of the control. (2) The CD(3) and CD(4) cell counts of the group with bacterial infection were lower than those of the control group. (3) The serum IgA concentration of the group with viral and mycoplasmal infection was higher than those of the control group and the group with unknown infection. (4) The serum IgM concentration of the group with bacterial infection was higher than those of the control group. (5) There were no significant differences in CD(8) cell counts, CD(4)/CD(8), concentration of serum IgG and IgG(1 - 4) between pneumonia group and the control group, and among various infectious groups and the control.</p><p><b>CONCLUSION</b>Pathogens of neonatal infectious pneumonia in Chengdu area included single viral or mycoplasmic infection or bacterial infection, viral and mycoplasmal infection with bacterial infection, and unknown infection. Immunological changes of newborn infants suffered from infectious pneumonia included declined CD(3) and CD(4) cell counts, particularly in bacterial infection.</p>