Prognostic implications and functional enrichment analysis of LTB4R in patients with acute myeloid leukemia / 南方医科大学学报

OBJECTIVE@#To explore the expression patterns, prognostic implications, and biological role of leukotriene B4 receptor (LTB4R) in patients with acute myeloid leukemia (AML).@*METHODS@#We collected the data of mRNA expression levels and clinical information of patients with AML from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database for mRNA expression analyses, survival analyses, Cox regression analyses and correlation analyses using R studio to assess the expression patterns and prognostic value of LTB4R. The correlation of LTB4R expression levels with clinical characteristics of the patients were analyzed using UALCAN. The co-expressed genes LTB4R were screened from Linkedomics and subjected to functional enrichment analysis. A protein-protein interaction network was constructed using STRING. GSEA analyses of the differentially expressed genes (DEGs) were performed based on datasets from TCGA-LAML stratified by LTB4R expression level. We also collected peripheral blood mononuclear cells (PBMCs) from AML patients and healthy donors for examination of the mRNA expression levels of LTB4R and immune checkpoint genes using qRT-PCR. We also examined serum LTB4R protein levels in the patients using ELISA.@*RESULTS@#The mRNA expression level of LTB4R was significantly increased in AML patients (4.898±1.220 vs 2.252±0.215, P < 0.001), and an elevated LTB4R expression level was correlated with a poor overall survival (OS) of the patients (P=0.004, HR=1.74). LTB4R was identified as an independent prognostic factor for OS (P=0.019, HR=1.66) and was associated with FAB subtypes, cytogenetic risk, karyotype abnormalities and NPM1 mutations. The co- expressed genes of LTB4R were enriched in the functional pathways closely associated with AML leukemogenesis, including neutrophil inflammation, lymphocyte activation, signal transduction, and metabolism. The DEGs were enriched in differentiation, activation of immune cells, and cytokine signaling. Examination of the clinical serum samples also demonstrated significantly increased expressions of LTB4R mRNA (P=0.044) and protein (P=0.008) in AML patients, and LTB4R mRNA expression was positively correlated with the expression of the immune checkpoint HAVCR2 (r= 0.466, P=0.040).@*CONCLUSION@#LTB4R can serve as a novel biomarker and independent prognostic indicator of AML and its expression patterns provide insights into the crosstalk of leukemogenesis signaling pathways involving tumor immunity and metabolism.

Preliminary study on common molecular markers between endometriosis and ovarian cancer / 肿瘤研究与临床

Objective To determine common molecular markers between endometriosis and ovarian cancer . Methods The specimens from 31 endometriosis patients who underwent laparoscopic excision , 28 other disease patients with normal oarium and 35 ovarian cancer patients who received the ovariectomy were collected. Expressions of transforming growth factor β1 (TGF-β1), cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF), estrogen receptor 1α(ER-1α), progesterone receptor (PR), androgen receptor (AR) and aromatase (CYP19) were detected by real-time reverse transcription polymerase chain reaction (RT-PCR). Results Compared with those in normal oarium group, the mRNA levels of TGF-β1, VEGF, ER-1α, AR, CYP19 and COX-2 in endometriosis group were increased by 2.05 fold, 2.20 fold, 3.32 fold, 1 . 45 fold , 3 . 19 fold and 3 . 00 fold , respectively , and the mRNA level of PR was reduced by 69 % ( all P< 0.05), while those in ovarian cancer group were increased by 5.61 fold, 7.61 fold, 7.49 fold, 4.79 fold, 7.76 fold and 5.35 fold, respectively, and the mRNA level of PR was reduced by 95 % (all P< 0.05). Conclusion In endometriosis and ovarian cancer tissues, the expression levels of TGF-β1, COX-2, VEGF, ER-1α, AR and CYP19 are increased, and the expression levels of PR are decreased, which maybe suggest both diseases are potentially relevant.

CDH13 Genetic Polymorphisms, Adiponectin and Ischemic Stroke: a Chinese Family-based Sib-pair Study / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To understand the relationships between CDH13 (T-cadherin) genetic polymorphisms, adiponectin levels and ischemic stroke, and possible interactions between CDH13 polymorphisms and other risk factors.</p><p><b>METHODS</b>We recruited 342 Chinese ischemic stroke sib pairs. We genotyped rs4783244 and rs7193788 on CDH13 using time-of-flight mass spectrometry genotyping technology and measured total and high-molecular weight (HMW) adiponectin levels. We investigated associations between SNPs and ischemic stroke, and interactions between SNPs and other risk factors using multi-level mixed-effects regression model.</p><p><b>RESULTS</b>In individuals without ischemic stroke, CDH13 rs4783244 was associated with total adiponectin levels (per T: Coef = -0.257, P = 0.001). CDH13 rs7193788 was associated with total adiponectin levels (per A: Coef = -0.221, P = 0.001) and HMW adiponectin levels (per A: Coef = -0.163, P = 0.003). rs7193788 was significantly associated with ischemic stroke (GA/AA vs. GG: OR = 1.55, 95% CI: 1.07 to 2.24, P = 0.020) after Bonferroni correction (α = 0.025). There was an interaction between rs7193788 and diabetes (P = 0.036). Compared to diabetes-free individuals with rs7193788 GG genotype, diabetes patients with rs7193788 GA/AA genotypes had higher risks for ischemic stroke (OR = 2.64, 95% CI: 1.58-4.40, P < 0.001).</p><p><b>CONCLUSION</b>CDH13 genetic polymorphisms are associated with adiponectin levels and ischemic stroke. An interaction is found between CDH13 SNP and diabetes for ischemic stroke.</p>

Systematic Evaluation onYupingfeng Granules Combined with Western Medicine in the Treatment of Children with Recurrent Respiratory Tract Infections / 中国中医药信息杂志

ObjectiveTo evaluate clinical efficacy ofYupingfeng Granules combined with western medicine for children with recurrent respiratory tract infection (RRTI).Methods CNKI, VIP, WANFANG DATA, SinoMed, PubMed, Embase, and Cochrane Library were searched for the randomized controlled trials (RCTs) that investigated the clinical and immune effects ofYupingfeng Granules in children with RRTI from inception to October 2015. Two researchers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of included studies. Then Meta analysis was performed through the software RevMan 5.3.Results A total of 8 articles involving 550 patients were included. The results of Meta analysis showed effective rate ofYupingfeng Granules combined with western medicine for children with RRTI [OR=4.16, 95%CI (2.49, 6.95),P0.05). ConclusionYupingfeng Granules combined with western medicine can improve effective rate, antibody level and T-cell level in the treatment of children with RRTI. The overall clinical efficacy is better than single western medicine treatment. However, RCTs with large samples, multiple centers and high quality are needed for further verification.

BACE1 inhibitors: From peptide mimics to small molecules / 国际药学研究杂志

Alzheimer’s disease(AD)is a chronic neurodegenerative disorder. According to the amyloid cascade hypothesis, abnormal accumulation of amyloid peptides(Aβ)in the brain resulting in neuronal toxicity is the main cause of AD. β-secretase1 (BACE1)is a rate-limiting enzyme that hydrolyzes β-amyloid precursor protein(β-APP)to produce amyloid peptides(Aβ). Therefore, BACE1 has been considered to be an attractive therapeutic target for the treatment of AD. Different structural classes of BACE1 inhibitors have been designed and developed since BACE1 was cloned and identificated. This review highlights the core scaffold to summarize the evolution of structure-based design of BACE1 inhibitors.

Clinical observation of axial offset after treatment by Ilizarov bone transport technology / 中国骨伤

<p><b>OBJECTIVE</b>To observe the incidence, causes and deviation angle of axial offset in patients with fracture ununited treated by Ilizarov bone transport technology.</p><p><b>METHODS</b>From January 2007 to December 2012, 10 patients with fracture ununited were treated by Ilizarov bone transport including 8 males and 2 females with an average age of (30.3 ± 10.6) years old ranging from 18 to 49 years old. The segment of bone defect involved upper tibial in 2 cases, medial tibia in 2 cases, lower tibial in 5 cases, upper femoral in 1 case. For Paley type of bone defect, 6 cases were type B1, 4 cases were B3. The incidence and deviation angle of axial offset after Ilizarov bone transport technology were observed and evaluated on bone result by Paley assessment.</p><p><b>RESULTS</b>All patients were followed up from 19 to 32 months with an average of (22.0 ± 5.6) months. Three cases were natural healed at fracture ends, the other 7 cases were healed after bone graft. The time of external fixator was 16 to 28 months. At the last follow-up, there were 3 cases occurred coronal angulation of angle 5° to 11° with an average of (8.7 ± 3.2). Sagittal angulation was in 4 cases, angle 6° to 9° with an average of (8.5 ± 2.1)°. There were 4 cases occurred axial offset. In the last follow-up, according to Paley evaluation criteria, osseous results were excellent in 7 cases, good in 3 cases; functional results were excellent in 6 cases, good in 4 cases.</p><p><b>CONCLUSION</b>Axial deviation after the Ilizarov bone transport treatment is relatively common, which will result in delayed healing of bone and poor limb alignment. In order to improve the bone healing, corresponding measurements should be taken to avoid or reduce the incidence of axial deviation during and after the operation.</p>

Study on the association between leukotriene A4 hydrolase gene polymorphism and ischemic stroke / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the association between polymorphism of leukotriene A4 hydrolase (LTA4H) gene among ischemic stroke patients and the related subtypes in the discordant sib pairs.</p><p><b>METHODS</b>Families including ischemic stroke patients and their siblings were recruited. Four single nucleotide polymorphisms (SNPs) of LTA4H as rs2072512, rs2540489, rs2540500 and rs6538697 were selected. Generalized estimating equation (GEE) was used to adjust for in-family correlation in the analysis of discordant sib pairs. Conditional logistic regression model and family based association test (FBAT) were both used to test the associations of LTA4H gene with ischemic stroke and its subtypes.</p><p><b>RESULTS</b>In total, data from 356 discordant sib pairs from 234 ischemic stroke patient pedigrees were analyzed. Results of GEE showed that hypertension, diabetes mellitus and hyperlipoidemia were associated with ischemic stroke. According to the association test results, rs2540489 G allele was found to be associated with ischemic stroke, both in the additive model (OR = 0.62, 95% CI: 0.41-0.94) and in the recessive model (OR = 0.48, 95% CI: 0.23-1.02). For two main ischemic stroke subtypes, rs2540489 G allele was found to be associated with large-artery atherosclerosis stroke in the additive model (OR = 0.48, 95% CI: 0.24-0.95) and in the recessive model (OR = 0.25, 95% CI: 0.07-0.93). After adjusting age, sex and other factors, the associations mentioned above, still existed.</p><p><b>CONCLUSION</b>rs2540489 polymorphism in LTA4H gene seemed to be associated with large-artery atherosclerosis stroke.</p>

A matched case-control study of risk factors in abdominal aortic aneurysm / 北京大学学报(医学版)

Objective:To examine the potential influence factors of abdominal aortic aneurysm (AAA).Methods:A 1∶2 pair-matched, case-control study was conducted from July 2011 to December 2012 .A pair was composed of one AAA patient recruited from the Vascular Surgery Department , Chinese PLA General Hospital and two gender-and age-matched non-AAA subjects , one from the same hospital and the other from the community in Fangshan District in Beijing .Demographic data , medical history and the lifestyle of each subject were collected .Moreover , all the participants underwent abdominal ultra-sound or computed tomography ( CT ) and peripheral venous blood samples were obtained .Results:There were 155 case/control pairs .The multivariate conditional logistic regression model confirmed that suffering from hypertension conferred a 1.98-fold (95%CI 1.12-3.18) increased likelihood of AAA. Smoking was a strong independent risk factor of AAA , with odds ratios ( 95% confidence intervals ) of 5.23 (2.44-11.23).Dyslipidemia(OR=2.61,95%CI 1.45-4.70), a higher level of serum hs-CRP (OR=2.43,95%CI 1.37-4.31) and homocysteine (OR=2.73,95%CI 1.61-4.65) were all asso-ciated with AAA.Conclusion: Hypertension and smoking are the risk factors of AAA .Dyslipidemia, hsCRP and Hcy are associated with AAA .

Relationship between genetic polymorphisms of β2-adrenergic receptor gene and essential hypertension risk among the Han Chinese population: a Meta analysis / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between A46G and C79G polymorphisms in the β2-adrenergic receptor (ADRB2) gene and the incidence of essential hypertension (EH) among the Han Chinese population.</p><p><b>METHODS</b>We conducted a computer retrieval of PUBMED, EMBASE, CNKI, Wanfang and VIP databases prior to May 2010. Articles investigating the relationship of EH and ADRB2 gene polymorphism of Han group were found through literature search, including 15 articles on A46G and 10 articles on C79G. According to the including and excluding criteria, a Meta-analysis was conducted in EH and ADRB2 gene polymorphism of A46G and C79G. The association was examined by RevMan4.2 software through quantitative analysis.</p><p><b>RESULTS</b>Eight articles on A46G polymorphism (including 1078 EH cases and 788 control subjects) and six articles on C79G polymorphism (including 1367 EH cases and 1006 control subjects) were included in the current study. Meta-analysis showed that there was a significant association between A46G polymorphism and EH: genotype GG/(AA + AG) (fixed-effected model, OR = 1.35, 95%CI = 1.04 - 1.74, P = 0.02), genotype GG/AA (fixed-effected model, OR = 1.41, 95%CI = 1.06 - 1.89, P = 0.02). No significant association was found between C79G polymorphism and EH of Han group in China: G/C allele comparison (random-effected model, OR = 0.88, 95%CI = 0.55 - 1.39, P = 0.57).</p><p><b>CONCLUSION</b>Significant association was found between A46G polymorphism of ADRB2 gene and EH, whereas no association could be found between C79G polymorphism and EH among Han Chinese population.</p>