2005～2008年广东省诺如病毒胃肠炎暴发的分子流行病学特征

为研究广东省诺如病毒胃肠炎暴发疫情的分子流行病学特点,我们采集了2005～2008年期间24起急性暴发性胃肠炎患者的粪便和肛拭子标本,使用诺如病毒特异性引物,通过逆转录-聚合酶链反应(RT-PCR)技术进行检测,再经核苷酸序列测定以分析诺如病毒的基因型,同时收集急性暴发性胃肠炎患者的相关流行病学资料。结果显示:24起急性暴发性胃肠炎中19起由诺如病毒引起,时间主要集中在每年的10月至次年2月,2005年病毒胃肠炎暴发疫情是由GⅡ-3基因型病毒引起,主要为幼儿园和小学,发生地主要在内陆山区,2006年秋季疫情以后则均为GⅡ-4型的变异株2006b引起,主要为大学和社区,2007年疫情数比其他年份高1倍,发生地遍及广东全省。广东省诺如病毒变异株2006b在个别特殊的基因位点呈现出高度的地域一致性。随着诺如病毒流行株的基因型由GⅡ-3变为GⅡ-4型,广东省诺如病毒流行的强度大大增加,新出现诺如病毒变异株2006b引起的暴发波及地方多,涉及人群从低幼儿童为主扩展到全年龄组,表明GⅡ-4新变异株比其它毒株具有更高的侵袭力。     

浙江省2019年儿童腺病毒肺炎流行病学特征分析

为了解浙江地区腺病毒肺炎的流行病学和病原学特征,本研究统计分析了2019年1月至2019年12月浙江大学医学院附属儿童医院腺病毒肺炎患儿的基本临床资料;并前瞻性的通过聚合酶链式反应(PCR)随机对部分的腺病毒阳性的肺炎患儿咽拭子进行基因扩增、测序和分型鉴定;进而构建系统发育树分析其核苷酸序列进化情况。本研究共检测咽拭子标本19650份,其中腺病毒阳性标本有4032份,腺病毒检出率为20.5%;春季和夏季腺病毒肺炎的患病率相对较高,患儿年龄主要在1~7岁。本研究所检测的99株腺病毒阳性标本经与GenBank数据库比对均为HAdV-3,通过Hexon基因全长系统进化分析得出,所检出的HAdV-3腺病毒均为Clade2进化分支。2019年浙江地区存在儿童HAdV-3肺炎的暴发流行,该病毒株未发生大的变异,均为Clade2进化分支。1~7岁的儿童为主要的易感人群。     

Role of Chemokines in Renal Cell Carcinoma

With new frontiers of pharmaceutical therapies focusing on tumor growth and angiogenesis, understanding the interaction between immune system and tumor microenvironment has become ever more important. Chemokines and chemokine receptors appear to play an integral role in tumor characteristics. Evidence suggests CXCR4, CXCL5, CXCR7, and stromal derived factor-1 appear to be crucial in survival, growth, and metastasis of renal cell carcinoma. As the role of chemokines in renal cancer is becoming more evident, further research will lead to a better understanding of tumor biology and the development of new therapeutic targets to help improve survival.Key words: Chemokine, Cytokines, Renal cell carcinoma, OncocytomaRenal cell carcinoma (RCC) is the seventh most common malignant condition among men and twelfth among women, representing 2% to 3% of all cancers.¹ Thirty to 40% of affected patients present with stage III or stage IV disease. It has an estimated incidence of 57,760 per year, which has increased 2% to 3% per year with no significant decrease in mortality rates.² Median survival of patients with metastatic disease is merely 13 months.¹ Studies have established that tumor and stroma interact through a variety of cytokines, chemokines, and growth factors.³ Recent evidence suggests chemokines may facilitate tumor growth, survival, and metastatic potential of various cancers including RCC. Chemokines have a potential to be utilized as tumor markers and novel targets of antiangiogenic therapy. Investigating the role of various chemokines in the development and metastasis of cancer has become a major focus of contemporary research. We examined the relevant literature and present a review of selected chemokines and their roles in renal cell cancers.     

1961-2005年东北地区气温和降水变化趋势

利用东北地区96个气象站1961-2005年的日平均气温和日降水量资料,采用线性倾向率法,累积距平法,Mann-Kendall法和Morlet小波分析等方法,对东北地区近45年来的气候变化和突变现象进行了研究.结果表明:近45年来,东北地区年平均气温变化在2.45-5.72℃之间,年均温呈现显著上升趋势,气候倾向率为0.38 ℃/10 a(P＜0.01),1988-1989年间发生了由低温到高温的突变;东北地区四季平均气温均呈现增高的趋势,其中冬季气温增幅最大,气候倾向率达到0.53℃/10 a,夏季气温增幅最小,0.24 ℃/10 a.东北地区年均温和季节均温年代际变化亦呈现明显的增暖趋势,年均温,春季均温和冬季均温均在1981-1990年开始变暖,夏季均温和秋季均温在1991-2000年开始变暖.东北地区气温增暖幅度随纬度的升高而增大,大兴安岭北部和小兴安岭地区是增温最明显的地区,增暖幅度较小的地区为辽河平原,辽东半岛和长白山南部地区.东北地区年降水量变化在430.40-678.72 mm之间,降水量变化趋势不明显,整体呈现减少趋势,气候倾向率为-5.71 mm/10 a(P＞0.05),1981-1990年为降水最多的年代,1982-1983年间发生了降水量由少到多的突变.四季降水量变化呈现不同的趋势,其中春季和冬季降水量呈现增多的趋势,夏季和秋季降水量呈现减少的趋势.降水量减少较明显的地区为辽东半岛和长白山南段,降水量增多较明显的地区为大兴安岭北部和松嫩平原.Morlet小波分析结果表明,东北地区年平均气温存在11a的强显著周期,此外还有24 a和6a尺度的变化周期;东北地区年降水量存在16a的强显著周期和6 a的小尺度变化周期.通过以上分析,近45 a东北地区总体气候呈现明显暖干化趋势.     

去泛素化酶在肾细胞癌中的作用

肾细胞癌（renal cell carcinoma,RCC）是成人肾脏的原发性恶性肿瘤。泛素-蛋白酶体系统（ubiquitin-proteasome system,UPS）对控制蛋白质水平和调节生理病理过程至关重要。去泛素化酶（deubiquitinases,DUBs）是UPS的关键成分,特别是从靶蛋白中去除泛素链,通过严格调节正常生理学中泛素化和去泛素化之间的平衡,对蛋白质稳态和质量控制显示出至关重要的作用。越来越多的研究表明,功能异常的DUBs与RCC的进展和转移有关。根据底物的不同,一些DUB可能会抑制RCC,而另一些则促进。本文综述了RCC相关DUB的最新研究进展,描述了其分类、功能作用,总结了DUB在RCC中的作用和作用机制,并讨论了靶向DUBs用于癌症治疗。     

Epidemiology of Birth Defects Based on a Birth Defect Surveillance System from 2005 to 2014 in Hunan Province,China

Objective

To describe the epidemiology of birth defects (BDs) in perinatal infants in Hunan Province, China, between 2005 and 2014.

Methods

The BD surveillance data of perinatal infants (for stillbirth, dead fetus or live birth between 28 weeks of gestation and 7 days after birth) were collected from 52 registered hospitals of Hunan between 2005 and 2014. The prevalence rates of BDs with 95% confidence interval (CI) and crude odds ratio (ORs) were calculated to examine the associations of infant gender, maternal age, and region (urban vs rural) with BDs.

Results

From 2005 to 2014, there were a total of 925413 perinatal infants of which 17753 had BDs, with the average prevalence of 191.84 per 10000 PIs (perinatal infants), showing a significant uptrend. The risks of BDs are higher in urban areas versus rural areas (OR = 1.20), in male infants versus female infants (OR = 1.19), and in mothers above age 35 versus those below age 35 (OR = 1.24). The main five types of BDs are Congenital heart defects (CHD), Other malformation of external ear (OMEE), Polydactyly, Congenital malformation of kidney (CMK), and Congenital talipes equinovarus (CTE). From 2005 to 2014, the prevalence rates (per 10000 PIs) of CHD and CMK increased significantly from 22.56 to 74 (OR = 3.29, 95%CI: 2.65–4.11) and from 7.61 to 14.62 (OR = 1.92, 95%CI:1.30–2.84), respectively; the prevalence rates of congenital hydrocephalus and neural tube defects (NTDs) decreased significantly from 11.8 to 5.29 (OR = 0.45, 95%CI: 0.31–0.65) and from 7.87 to 1.74 (OR = 0.22, 95%CI: 0.13–0.38), respectively.

Conclusions

The prevalence rates of specific BDs in perinatal infants in Hunan have changed in the last decade. Urban pregnant women, male perinatal infants, and mothers above age 35 present different prevalence rates of BDs. Wider use of new diagnosis technology, improving the ability of monitoring, strengthening the publicity and education are important to reduce the prevalence of BDs.     

Relevance and Therapeutic Possibility of PTEN-Long in Renal Cell Carcinoma

PTEN-Long is a translational variant of PTEN (Phosphatase and Tensin Homolog). Like PTEN, PTEN-Long is able to antagonize the PI3K-Akt pathway and inhibits tumor growth. In this study, we investigated the role PTEN-Long plays in the development and progression of clear cell renal cell carcinoma (ccRCC) and explored the therapeutic possibility using proteinaceous PTEN-Long to treat ccRCC. We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt). Gain of function experiments showed overexpression of PTEN-Long in the ccRCC cell line 786-0 suppressed PI3K-Akt signaling, inhibited cell proliferation, migration and invasion, and eventually induced cell death. When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage. Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model. Our results implicated that understanding the roles of PTEN-Long in renal cell carcinogenesis has therapeutic significance.     

Computational Modelling of Metastasis Development in Renal Cell Carcinoma

The biology of the metastatic colonization process remains a poorly understood phenomenon. To improve our knowledge of its dynamics, we conducted a modelling study based on multi-modal data from an orthotopic murine experimental system of metastatic renal cell carcinoma. The standard theory of metastatic colonization usually assumes that secondary tumours, once established at a distant site, grow independently from each other and from the primary tumour. Using a mathematical model that translates this assumption into equations, we challenged this theory against our data that included: 1) dynamics of primary tumour cells in the kidney and metastatic cells in the lungs, retrieved by green fluorescent protein tracking, and 2) magnetic resonance images (MRI) informing on the number and size of macroscopic lesions. Critically, when calibrated on the growth of the primary tumour and total metastatic burden, the predicted theoretical size distributions were not in agreement with the MRI observations. Moreover, tumour expansion only based on proliferation was not able to explain the volume increase of the metastatic lesions. These findings strongly suggested rejection of the standard theory, demonstrating that the time development of the size distribution of metastases could not be explained by independent growth of metastatic foci. This led us to investigate the effect of spatial interactions between merging metastatic tumours on the dynamics of the global metastatic burden. We derived a mathematical model of spatial tumour growth, confronted it with experimental data of single metastatic tumour growth, and used it to provide insights on the dynamics of multiple tumours growing in close vicinity. Together, our results have implications for theories of the metastatic process and suggest that global dynamics of metastasis development is dependent on spatial interactions between metastatic lesions.     

2014年陕西省柯萨奇病毒A10型相关手足口病的流行特征和其VP1区基因特征研究

了解陕西省手足口病(Hand,foot and mouth disease,HFMD)的致病病原体柯萨奇病毒A10型(CV-A10)的流行特征及VP1区基因特征。对2014年收集的HFMD病例标本,通过荧光定量PCR检测确定肠道病毒型别,对CV-A10引起的HFMD流行特征进行描述性分析。使用RD细胞进行病毒分离,RT-PCR扩增CV-A10的VP1区基因片段并进行序列测定,使用Meg Align软件进行核苷酸及氨基酸的同源性分析,并使用MEGA5.0软件构建系统进化树。2014年CV-A10是陕西HFMD病原谱中的第三大病原,占其他肠道病毒的57.71%,13例重症HFMD病例的致病病原体鉴定为CV-A10,占重症病例的9.03%。CV-A10感染HFMD病例以≤3岁年龄组儿童为主(83.07%),男女性别比为1.15∶1。发病时间主要集中在4～7月。实验室分离出101株CV-A10,覆盖全省10市(区)。完成测序的18株CV-A10核苷酸和氨基酸同源性分别为94.0%～100.0%和97.3%～100.0%,与A型原型株的核苷酸和氨基酸同源性分别为76.2%～77.5%和91.9%～93.0%,与近年来河北、湖南和河南地区流行株具有较高的同源性。系统进化显示陕西CV-A10分离株属于C基因型。CV-A10是2014年陕西HFMD的优势病原,能引起重症HFMD,本次分离到的CV-A10毒株均属于C基因型。     

Unique Characteristics and Outcomes of Patients Diagnosed With Both Primary Thyroid and Primary Renal Cell Carcinoma

Objective: Patients with multiple primary malignancies may exhibit unique clinical characteristics that suggest a common predisposition or lead to different disease management. Given the association of primary thyroid (TC) and renal cell carcinoma (RCC), we characterized the clinicopathologic features of patients treated for both malignancies (TC/RCC).Methods: TC/RCC patients were identified through the institutional tumor registry and using data compiled by retrospective chart review. To compare with broader institutional and national cohorts, we examined patients admitted with TC or RCC institution-wide and reviewed the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for these cancers.Results: Overall, 51% of patients developed TC before RCC, 27% developed RCC before TC, and 22% were diagnosed within 1 year of each other. The mean age at TC diagnosis was 52 ± 15 (18–77), which was significantly older than institutional TC patients (45 ± 16.5 years, P≤.0001), and the mean age at RCC diagnosis was 59 ± 12 (32–79). The TC/RCC cohort had a balanced sex distribution (51% female) compared with the institutional TC group (67% female, P = .0003) and the institutional RCC group (31% female, P<.0001). Similar age and sex ratio differences were seen when compared with SEER cohorts. In the TC/RCC cohort, 43% of patients developed other cancers (52% of females, 33% of males; P = .04); among the females, 45% developed breast cancer.Conclusion: Individuals who develop both TC and RCC may represent a unique subset of cancer patients. Further prospective research is warranted to explore the unanticipated association with breast cancer in female patients and to investigate a possible common pathogenesis underlying these malignancies.Abbreviations: RCC = renal cell carcinoma SEER = Surveillance, Epidemiology, and End Results SPC = second primary cancer SPTC = subsequent primary thyroid cancer TC = thyroid cancer VHL = von Hippel-Lindau     

肾癌相关基因克隆——肾癌cDNA消减文库的构建

应用抑制性消减杂交技术,构建人肾癌与正常肾差异表达的cDNA消减文库.分别从肾癌及正常肾细胞系中提取poly(A)⁺RNA,依次合成单链及双链cDNA,经酶切成平均大小为400～600 bp的片段,将肾癌cDNA分为两组,分别与两种不同的接头衔接,再与正常肾cDNA进行两次消减杂交及两次抑制性PCR后,将产物与T/A载体连接构建成功cDNA消减文库,并转染大肠杆菌进行文库扩增.构建成功具有高消减效率的人肾癌cDNA消减文库,非特异性cDNA片段被有效地消减,特异表达的cDNA得到富集.文库扩增后得到6 500个克隆,随机挑取350个制备质粒,酶切分析均得到400～600 bp插入片段.所构建的人肾癌cDNA消减文库为进一步大批量筛选、克隆肾癌特异性表达的未知新基因奠定了基础.     

肾透明细胞癌相关微小RNA的研究进展

微小核糖核酸(miRNAs)是一类长约22个核苷酸的非编码单链小核糖核酸分子,miRNA通过与靶mRNA 3'端非翻译序列完全或部分互补结合,导致靶mRNA降解或转录后翻译抑制,从而调控靶基因的表达.最新研究显示人类血清/血浆中miRNA表达稳定,并在肿瘤患者血清中发现多种miRNA,其中的一些已经被证实与肾癌发生及发展相关,以往miRNA与肾癌的研究方.向多集中于肾癌组织,尽管发现很多有差异的miRNA,但不同研究者之间的结果常难以相互验证,而最近研究证实血清miRNA具有组织相关性和器官特异性,并对某些肿瘤具有高敏感性和特异性,因此其有望成为新的肿瘤标志物.肾癌是国内泌尿系统的第二常见恶性肿瘤,而且其近年来发病率和死亡率有逐年增高的趋势.由于肾透明细胞癌是肾癌的主要亚型,因此本文就血清miRNA在肾透明细胞癌的表达及其作用的研究进展作一综述.     

中国山西省大型木材腐朽菌多样性研究（英文）

2004–2016年对山西省8个保护区和森林公园天然林中的木材腐朽菌进行了真菌资源调查,共采集木生真菌标本1 000余号,基于对这些标本的研究,鉴定出木生真菌160种,分属于77个属,38个种为山西省首次报道。此外Antrodiella onychoides和Phlebiopsis pilatii为中国新记录种,本文提供了这2个种的详细描述、ITS序列和n LSU序列。     

VEGF和Survivin在肾癌中的表达及其相关性研究

目的:探讨肾癌组织中血管内皮生长因子VEGF与凋亡抑制蛋白Survivin表达的相关性及其之间的关系,研究Survivin和VEGF在肾癌发生发展中的作用机制。方法:应用免疫组织化学方法检测70例肾癌组织和70例癌旁正常肾脏组织中VEGF和Survivin的表达,并将检测结果与临床病理特征进行综合分析。结果:VEGF和Survivin在肾癌中表达均高于癌旁正常肾脏组织;Survivin和VEGF在肾癌中的阳性表达率分别为75.71%(53/70)和72.86%(51/70),在癌旁肾脏组织中的表达率分别为0%(0/70)、17.14%(12/70),差异均有显著性意义(P0.05);VEGF和Survivin的表达与患者的性别、年龄、肿瘤大小、病理分级均无相关性;VEGF和Survivin表达呈正相关性。结论:VEGF和Survivin在肾癌组织中表达率较高,为肾癌的分子靶向治疗提供了新的靶点。Survivin和VEGF在RCC中的表达关系密切,测定RCC中Survivin、VEGF蛋白的表达,有助于临床判断病人预后。     

鞍区颗粒细胞瘤1 例的病历分析及相关文献复习

目的：探讨伴有临床症状的鞍区颗粒细胞瘤(granular cell tumour,GCT)的病理组织学起源及其治疗方法。方法：回顾性分析 我院收治的1 例具有临床症状的GCT 患者的治疗状况和病理结果,并结合近20 年来关于GCT 病理和治疗的相关文献报道,探 讨GCT 肿瘤病理组织起源和治疗要点。结果：该患者影像学报告怀疑鞍区炎性肉芽肿,给予抗生素治疗后复查MRI 显示鞍区占 位较前次无改变,增强MRI可见占位明显强化,诊断良性肿瘤,并采取翼点入路手术切除。术后病理证实为神经垂体颗粒细胞瘤。 术后患者头痛缓解,尿量、尿比重、垂体内分泌激素等相关指标相继恢复至正常值。结论：GCT 很可能起源于神经组织,伴有临床 症状的GCT 的治疗首选开颅手术,肿瘤残存的患者,术后不必放射治疗,定期复查即可。     

VEGF和Survivin在肾癌中的表达及其相关性研究

目的：探讨肾癌组织中血管内皮生长因子VEGF与凋亡抑制蛋白Survivin表达的相关性及其之间的关系,研究Survivin和VEGF在肾癌发生发展中的作用机制。方法：应用免疫组织化学方法检测70例肾癌组织和70例癌旁正常肾脏组织中VEGF和Survivin的表达,并将检测结果与临床病理特征进行综合分析。结果：VEGF和Survivin在肾癌中表达均高于癌旁正常肾脏组织;Survivin和VEGF在肾癌中的阳性表达率分别为75.71%（53/70）和72.86%（51/70）,在癌旁肾脏组织中的表达率分别为0%（0/70）、17.14%（12/70）,差异均有显著性意义（P〈0.05）;VEGF和Survivin的表达与患者的性别、年龄、肿瘤大小、病理分级均无相关性;VEGF和Survivin表达呈正相关性。结论：VEGF和Survivin在肾癌组织中表达率较高,为肾癌的分子靶向治疗提供了新的靶点。Survivin和VEGF在RCC中的表达关系密切,测定RCC中Survivin、VEGF蛋白的表达,有助于临床判断病人预后。     

肾癌患者凝血指标的临床分析

目的:探讨肾癌患者异常增高的凝血指标、静脉血栓栓塞症(VTE)发生率与临床分期的关系,分析肾癌患者血液高凝状态的临床特征。方法:对2010年至2012年335例住院的肾癌患者Fib、D-D、BPC水平进行检测并筛查发生VTE的患者。结果:335例肾癌患者中,异常Fib、D-D、BPC的发生率分别为20.6%、9.9%、6.6%,且随着肾癌分期的增加,凝血指标异常的发生率逐渐升高,各分期之间比较有统计学差异(P0.05);VTE的发生率为2.2%,Ⅳ期肾癌患者最高为1.2%,且各分期之间比较有统计学意义(P0.05)。年龄≥60岁、肿瘤最大径10 cm、临床分期晚、伴有远处转移的肾癌患者血液高凝的发生率分别显著高于年龄60岁、肿瘤最大径10 cm、临床分期早、不伴有远处转移的肾癌患者(P0.05)。结论:年龄≥60岁、肿瘤最大径10 cm、临床分期晚、伴有远处转移可能是肾癌患者发生血液高凝状态和VTE的危险因素,应引起临床重视。