An evolutionary analysis of nitric oxide reductase gene norV in enterohemorrhagic Escherichia coli O157

A novel virulence gene, norV, that encodes nitric oxide (NO) reductase, was examined to investigate the emergence of enterohemorrhagic Escherichia coli (EHEC) O157 subgroup C clusters 2 and 3 from subgroup C cluster 1. Deletion of norV occurred at a point between cluster 1 and cluster 2 just after or at the same time that an stx2 bacteriophage, which retains Shiga toxin 2 gene, was inserted into wrbA, which encodes a novel multimeric flavodoxin-like protein, in EHEC O157. Sensitivity of NO to anaerobic growth was correlated with the deletion of norV in all EHEC O157 individuals tested. The C467A mutation of fimH, which encodes minor component of type 1 fimbriae, occurred within cluster 1, not as a transition from cluster 1 to cluster 2, indicating that there is a cluster 1 minority branch that leads to cluster 2. These data refine the evolutionary history of an emerging EHEC O157.     

An Adrenal Incidentaloma Diagnosed as Dopamine-Secreting Pheochromocytoma: A Case Report

BackgroundDopamine-secreting pheochromocytomas are exceedingly rare.Case presentationA 28-year-old woman, who was admitted due to 4 hours of acute-onset abdominal pain, detected an adrenal mass incidentally. She was almost asymptomatic without a known family history. Laboratory assessments showed significant increases in dopamine levels of serum and 24-h urinary. By using preoperative a-adrenergic receptor blockers, she developed orthostatic hypotension and palpitations. When she underwent laparoscopic left adrenalectomy, she experienced rapid cyclic fluctuations in systolic blood pressure from 90 mmHg to 200 mmHg. Postoperatively, she exhibited prolonged hypotension, requiring vasopressor therapy and fluid replacement. According to histopathological diagnosis, it was a pheochromocytoma. Dopamine levels in 24-h urine and serum decreased to normal after operation. Analysis of specific gene SDHB, SDHD, RET, VHL and NF1 detected no pathogenic mutations.ConclusionPatients with dopamine-secreting pheochromocytomas are mostly asymptomatic, leading to a significant delay in diagnosis. There is a large possibility for dopamine-secreting pheochromocytomas to show a malignant tendency than the adrenergic and noradrenergic phenotypes. The a-adrenergic receptor blocker is not indicated for preoperative medical treatment because it can cause hypotension and cardiovascular failure. Calcium channel blockers or metyrosine may be better alternatives. All patients with pheochromocytomas should receive targeted genetic testing based on specific clinical features. SDHB, SDHD, RET, VHL and NF1 mutations are suggested for genetic testing of adrenal dopamine-secreting pheochromocytomas.     

Variant analysis and genotype/phenotype association study in 42 Chinese patients with Bartter syndrome type 3

Objective To analyze the variants of 42 Chinese patients with Bartter syndrome type 3 (BS3) and explore the characteristics of genotype and phenotype. Methods Forty-two genetically diagnosed patients from 40 Han and one Hui families were collected in the Affiliated Hospital of Qingdao University and the Affiliated Qingdao Municipal Hospital of Qingdao University during the period of June 2012 to October 2018. The second-generation sequencing and multiplex ligase probe-dependent amplification (MLPA) technique were used to analyze the CLCNKB gene variation and its characteristics in children with BS3. The clinical data were collected, and the therapeutic effect and growth improvement were observed and followed up. Thirty eight patients were divided into severe (n=26) and light (n=12) groups according to the severity of genetic variation. The clinical phenotypic characteristics of the two groups were compared. Results Thirty-six variants including 16 novel ones of CLCNKB gene were found. The whole gene deletion of CLCNKB gene was the most frequent mutation (40%), and the rate of large deletions was up to 55%. The most common symptoms included development retardation (38/42), polydipsia and polyuria (35/42), constipation (31/42) and vomiting (27/42). All patients presented with hypokalemia, hypochloremia and metabolic alkalosis. After the medicine treatment that based on indomethacin and potassium chloride, most patients could achieve obvious recovery of growth rate and restoration of hypokalemia. The severe group showed more severe metabolic alkalosis than the light group. Conclusions Thirty-six variants of CLCNKB gene have been found in this study, including 16 novel ones, which enrich the human gene mutation database (HGMD) and provide valuable references to diagnosis, treatment and the genetic counseling of Chinese population.     

Gene Expression Omnibus资源库在肿瘤学研究中的应用

Gene Expression Ominibus （GEO）是供学者们分享基因表达谱芯片数据、高通量测序数据等的国际化的公共资源平台,其中涵盖了应用炎癌模型获得的大量相关实验数据,比如关于某些炎性因子的表达情况.这些数据为炎癌转化中的调控网络和分子机制的研究提供了帮助,也为肿瘤的防治提供了新思路.研究者针对新的预测基因进行研究时,起源于各种疾病模型或实验处理的GEO数据库为寻找其有关功能提供了有利条件和有力证据.     

单羧酸转运蛋白1促进胰腺导管癌细胞浸润转移的机制研究

背景与目的：单羧酸转运蛋白1（monocarboxylate transporter 1，MCT1）是细胞转运乳酸、丙酮酸等代谢产物及能量物质的一种重要蛋白质，其在胰腺导管癌中的作用及机制鲜有研究报道。该研究旨在探讨MCT1在胰腺导管癌中的表达及临床病理学意义。方法：纳入78例胰腺导管癌患者的癌组织及癌旁正常组织，运用免疫组织化学技术检测MCT1在癌组织和癌旁正常组织中的表达水平并分析其临床病理学意义。在体外细胞系水平上，我们运用胰腺癌细胞系PANC-1和Capan-1，运用细胞克隆形成实验、细胞划痕和Transwell实验分析沉默MCT1后胰腺癌细胞增殖、迁移和浸润的改变。为明确MCT1的相关作用机制，我们通过生物信息学分析，预测miR-124-3p是MCT1的潜在调控微小RNA；为了进一步验证，我们运用双荧光素酶报告实验分析miR-124-3p对MCT1的调控效果；运用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）分别检测51对新鲜胰腺癌组织中MCT1和miR-124-3p的基因表达并分析两者的相关性。结果：MCT1的阳性表达主要位于细胞膜和细胞质。相比癌旁正常组织，MCT1在胰腺导管癌组织中显著高表达，其表达水平与胰腺导管癌的分化程度、临床分期、淋巴结转移和不良预后具有显著相关性。在体外细胞系水平上，沉默MCT1能够显著抑制胰腺癌细胞系PANC-1和Capan-1的增殖、迁移和浸润；miR-124-3p在胰腺癌组织中显著低表达，并且与MCT1 mRNA的表达具有显著负相关性，能够负调控MCT1的蛋白表达。结论：MCT1是胰腺导管腺癌的致癌基因，miR-124-3p能够负调控MCT1的表达。     

胃肝样腺癌的诊治现状

目的了解胃肝样腺癌(GHA)的研究现状,以期为临床诊治提供参考。方法查阅近年来国内外关于GHA研究的相关文献并进行综述。结果 GHA是一种具有腺样分化和肝细胞分化的特殊类型胃癌,在所有胃癌中发生率≤1%。GHA的组织学形态与肝细胞癌相似,常伴有血清甲胎蛋白升高,极易出现淋巴结转移和肝转移。根治性手术及化疗是其最主要的治疗方法,但即使是根治性切除后仍常见复发和转移,且目前尚无针对GHA的标准化疗方案。结论 GHA是一种恶性度较高的特殊胃癌亚型,临床进展迅速,预后差。组织病理学结果是诊断GHA的金标准。GHA治疗以手术与化疗为主的综合治疗方式,基因分子特征及靶向治疗是未来的研究方向。     

Self-organizing maps based on limit cycle attractors

Recent efforts to develop large-scale brain and neurocognitive architectures have paid relatively little attention to the use of self-organizing maps (SOMs). Part of the reason for this is that most conventional SOMs use a static encoding representation: each input pattern or sequence is effectively represented as a fixed point activation pattern in the map layer, something that is inconsistent with the rhythmic oscillatory activity observed in the brain. Here we develop and study an alternative encoding scheme that instead uses sparsely-coded limit cycles to represent external input patterns/sequences. We establish conditions under which learned limit cycle representations arise reliably and dominate the dynamics in a SOM. These limit cycles tend to be relatively unique for different inputs, robust to perturbations, and fairly insensitive to timing. In spite of the continually changing activity in the map layer when a limit cycle representation is used, map formation continues to occur reliably. In a two-SOM architecture where each SOM represents a different sensory modality, we also show that after learning, limit cycles in one SOM can correctly evoke corresponding limit cycles in the other, and thus there is the potential for multi-SOM systems using limit cycles to work effectively as hetero-associative memories. While the results presented here are only first steps, they establish the viability of SOM models based on limit cycle activity patterns, and suggest that such models merit further study.     

Methods for development of a core outcome set for clinical trials integrating traditional Chinese medicine and Western medicine

Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndrome- set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.