中国汉族人群家族性前列腺癌的初步研究

目的:以中国汉族人群为研究对象,估计家族性前列腺癌的发病率,分析家族史对于前列腺癌发生的作用及家族性前列腺癌的临床和病理学特点。方法:回顾性分析我院2014年7月～2016年7月行穿刺并证实为前列腺癌的598例患者的一级亲属前列腺癌家族史。采取病例对照研究分析前列腺癌家族史对于前列腺癌发生的作用,病例组选择年龄56～79岁的495例前列腺癌患者,对照组选择同期接受穿刺且结果为前列腺增生的患者,匹配条件为年龄、民族(汉)和居住地相同。通过比较两组发病年龄、BMI、确诊时的PSA中位数、肿瘤分期、Gleason评分、D’Amico危险因素分级和首要治疗方式,来探究家族性前列腺癌患者和散发性前列腺癌患者临床病理学特点的差异。结果:年龄56～79岁且具有前列腺肿瘤家族史的患者,其前列腺癌发病率显著高于同年龄无前列腺癌家族史的人群(RR=3.0,P=0.010)。598例在我院穿刺并确诊为前列腺癌的患者中,有25例(4.2%)是家族性前列腺癌患者。和散发性前列腺癌患者相比,家族性前列腺癌患者中分级属低或中度危险分级的比例更高,但差异无统计学意义(P>0.05),并且家族性前列腺癌患者更愿意接受根治手术作为其首要治疗方式(P<0.05)。结论:在中国,家族性前列腺癌发生率远低于西方国家。前列腺癌家族史显著增加中国男性前列腺癌的发病风险。家族性与散发性前列腺癌之间并无显著的临床及病理学差异,但家族性前列腺癌患者更愿意接受根治手术作为首要的治疗方式。     

Multiple Genes of the Renin-Angiotensin System Are Novel Targets of Wnt/β-Catenin Signaling

Activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of CKD and cardiovascular disease. However, current anti-RAS therapy only has limited efficacy, partly because of compensatory upregulation of renin expression. Therefore, a treatment strategy to simultaneously target multiple RAS genes is necessary to achieve greater efficacy. By bioinformatics analyses, we discovered that the promoter regions of all RAS genes contained putative T-cell factor (TCF)/lymphoid enhancer factor (LEF)-binding sites, and β-catenin induced the binding of LEF-1 to these sites in kidney tubular cells. Overexpression of either β-catenin or different Wnt ligands induced the expression of all RAS genes. Conversely, a small-molecule β-catenin inhibitor ICG-001 abolished RAS induction. In a mouse model of nephropathy induced by adriamycin, either transient therapy or late administration of ICG-001 abolished established proteinuria and kidney lesions. ICG-001 inhibited renal expression of multiple RAS genes in vivo and abolished the expression of other Wnt/β-catenin target genes. Moreover, ICG-001 therapy restored expression of nephrin, podocin, and Wilms’ tumor 1, attenuated interstitial myofibroblast activation, repressed matrix expression, and inhibited renal inflammation and fibrosis. Collectively, these studies identify all RAS genes as novel downstream targets of Wnt/β-catenin. Our results indicate that blockade of Wnt/β-catenin signaling can simultaneously repress multiple RAS genes, thereby leading to the reversal of established proteinuria and kidney injury.     

膝关节镜下中心成形联合边缘稳定术治疗外侧盘状半月板损伤

目的探讨关节镜下中心成形联合边缘稳定术治疗外侧盘状半月板损伤的疗效。方法收集自2009-01—2013-08诊治的盘状半月板损伤68例(72膝),经MRI和关节镜下确诊后,随机分成2组。A组给予保留边缘6~8 mm成形联合半月板稳定术,进行体部、肌腱裂口周围垂直缝合固定,前、后角经胫骨骨道固定;B组行盘状半月板全切或次全切除术。观察2组术后3、6、12膝关节功能Lysholm评分,术后12个月MRI半月板板台比。结果 A组34例获得随访,B组34例获得随访,随访时间平均12.3(12~14)个月。患者术后关节活动度恢复满意,关节交锁及弹响症状消失,无再撕裂或因症状复发需要二次手术者。2组术后3、6个月Lysholm评分差异无统计学意义(t=1.826,P=0.077;t=0.442,P=0.661);术后12个月A组Lysholm评分较B组高,差异有统计学意义(t=3.718,P=0.001)。A组术后12个月MRI半月板板台比为(9.2±2.6)%,B组为(5.0±2.7)%,A组残存半月板板台比较B组高,差异有统计学意义(t=3.475,P=0.001);但比同侧正常的(12.3%)低。结论对于不稳定盘状软骨损伤,在半月板成形的基础上,给予周边缝合固定及前后角重建固定,能最大程度地保留外侧半月板周缘并保持其稳定性,具有良好的短期疗效。     

Abundance of saccharides and scarcity of glycosaminoglycans in the soft tissue of clam, Meretrix meretrix (Linnaeus)

We investigated presence and distribution of glycosaminoglycans (GAGs) in Meretrix meretrix soft tissue by determining GAG composition in the different parts, namely, mantle edge, foot, gill, adductor muscle, and viscera. The occurrence of glycan ingredients was examined by histochemistry, whereas GAG and general polysaccharide contents in clam tissue were qualified through extraction and determination. Tissue sections stained with alcian blue or periodic acid–Schiff demonstrated the general existence of saccharides and trifling generation of GAGs in clam tissues. GAGs coexisting with glycogens appeared to be primarily produced in the mantle and foot tissues in mucus form by visualization. The GAG content of the polysaccharide extract ranged from 16.8 to 75.8?mg in 10?g of 5 dried tissue materials in comparison with total carbohydrate level in the range of 500–1760?mg, thereby indicating that GAGs were not the major components of polysaccharide extracts. GAG composition only accounted for approximately 4% of total glycan components, which consist of the determinations of amino sugar and uronic acid. The soft tissues of clam contained abundant saccharide compounds but sparse amounts of GAGs. The results will benefit the subsequent development of products made from the polysaccharide components of M. meretrix.     

Genetic polymorphisms,forensic efficiency and phylogenetic analysis of 15 autosomal STR loci in the Kazak population of Ili Kazak Autonomous Prefecture,northwestern China

Aim: We investigated the frequencies of 15 autosomal STR loci in the Kazak population of the Ili Kazak Autonomous Prefecture with the aim of expanding the available population information in human genetic databases and for forensic DNA analysis.

Subjects and methods: Genetic polymorphisms of 15 autosomal short tandem repeat (STR) loci were analysed in 456 individuals of the Kazak population from Ili Kazakh Autonomous Prefecture, northwestern China.

Results: A total of 173 alleles at 15 autosomal STR loci were found; the allele frequencies ranged from 0.5022–0.0011. The combined power of discrimination and exclusion statistics for the 15 STR loci were 0.999 999 999 85 and 0.999 998 800 65, respectively. In addition, phylogenetic analysis involving the Ili Uygur population and other relevant populations was carried out. A neighbour-joining tree and multidimensional scaling plot were generated based on Nei’s standard genetic distance.

Conclusions: Results of the population comparison indicated that the Ili Uygur population was most closely related genetically to the Uygur populations from other regions in China. These findings are consistent with the historical and geographic backgrounds of these populations.     

Screening HCV genotype-specific epitope peptides based on conserved sequence analysis and B cell epitope prediction in HCV E2 region

The high mutation rate of the hepatitis C virus (HCV) genome increases the genotype diversity and renders the detection of the virus more difficult. Therefore, prediction and assessment of highly conserved and strongly antigenic epitope polypeptide sequences have become a focus of current research. The E2 region is the target binding region of neutralizing antibodies. HCV genomics, especially the high mutation rate of E2 region sequence, makes its genotyping more and more diverse, and the detection of HCV and genotype is becoming more and more strict. In this study, four HCV B cell epitope polypeptides were constructed based on assessment of conserved sequences in the HCV E2 region and prediction of B cell epitopes, including sequences specific to genotype 1A (DC-13: 434-DTGWLAGLFYYHK-446), genotype 1B (HC-13: 434-HTGFLAALFYAKS-446), genotype 4D (NC-13: 434-NTGFLASLFYTHK-446), and a consensus sequence (FC-9: 447-FNSSGCPER-455). Epitope polypeptides combined with serum from 29 HCV-infected or 25 non-HCV-infected individuals were assayed by enzyme-linked immunosorbent assay (ELISA), and differences were analyzed by T/T’ test methods in SPSS v20.0 software. Binding levels of genotype 1A, 4D, and consensus epitope polypeptides with sera of HCV-infected patients were higher than those of non-infected individuals. Moreover, binding of genotype 1B epitope polypeptides with serum of HCV 1B-infected patients was higher than that of HCV 2A-infected patients. While the screening results of HCV genotype-specific epitope polypeptides were preliminary, these findings indicated that we successfully established an HCV and genotype serological ELISA detection method. Such an approach would facilitate the discovery of epitope polypeptides which may become new antigen candidates in peptide vaccine development for the prevention of HCV infection.     

Coculture with mesenchymal stem cells facilitates the proliferation of hematopoietic stem cells under different coculture modes北大核心

BACKGROUND: Although a large number of related studies have been carried out, there is still a lack of practical methods to amplify hematopoietic stem cells (HSCs) in vitro. Mesenchymal stem cells (MSCs) secrete a variety of cytokines that promote the HSCs proliferation and inhibit their differentiation. These cytokines play an important role in maintaining the hematopoietic microenvironment and regulating HSCs function. OBJECTIVE: To investigate the effect of bone marrow MSCs on the proliferation of HSCs in vitro under different coculture modes. METHODS: Mesenchymal stem cells from the bone marrow of C57BL/6 mice were cultured in vitro using the whole bone marrow adherent culture. CD117+ cells (HSCs) were sorted from passage 3 cells by using miniMACS magnetic beads sorting. Then, CD117+ cells were co-cultured with MSCs under different coculture models, including single culture of HSCs (control group), Transwell coculture (upper chamber, HSCs; lower chamber, MSCs) and two-dimensional contact coculture (coculturing HSCs and MSCs in 24-well platts). The morphology of HSCs was observed under phase contrast microscope and fluorescence microscope, and the number of active cells of HSCs was counted at 1,3,5, and 7 days after coculture. RESULTS AND CONCLUSION: During the coculture of 1-7 days, the number of HSCs in the two groups was increased with culture time (P < 0.05). After 3 days of coculture, HSCs in each group was grown into the logarithmic growth phase, and morphological changes in some HSCs were detected at 5 days of coculture. Ait 7 days of coculture, the viabilities of HSCs in different culture models were ranked as follows: single culture model < Transwell coculture model < two-dimensional contact coculture model (P < 0.05). These findings suggest that MSCs can effectively promote the proliferation of HSCs in vitro, and the promotion effect is increased under contact coculture conditions. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Current Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphocytic Leukemia: Success,Failure and Future Perspectives—A Single-Center Experience, 2008 to 2016

Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed acute lymphoblastic leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T cell depletion used and, consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes among different donor types. One hundred and twenty-four pediatric patients underwent HSCT from a matched sibling donor (MSD; n?=?48), an unrelated matched donor (UMD; n?=?56), or a haploidentical donor (n?=?20). We observed a similar 3-year event-free survival (EFS) for MSD recipients (of .64) and for UMD recipients (.62), but a significantly lower EFS for recipients of haploidentical transplants (.35; P?=?.01). Relapse was the main cause of HSCT failure and was significantly higher in the haploidentical donor group (.47 versus .19 for MSD and .24 for UMD; P?=?.02). Treatment-related mortality was evenly distributed among the donor groups (.17, .16, and .15 for the MSD, UMD, and haploidentical groups, respectively). Rates of infection-related mortality were lower than previously reported. Relapse is the main obstacle for successful HSCT in the contemporary era, and this effect is most evident in recipients of haploidentical donor grafts. Newer methods to improve graft-versus-leukemia effect are being evaluated and will need to be incorporated into the management of high-risk patients.