PERK信号通路介导结肠癌细胞对5-氟尿嘧啶耐药机制的研究

目的:观察PERK蛋白对结肠癌细胞药物敏感性的影响，并进一步探讨其相关作用机制。方法:结肠癌细胞系HCT116分为三组:空白对照（Control）组、下调PERK表达（si-PERK）组、阴性对照（si-NC）组；采用免疫荧光及RT-PCR验证转染效率；利用CCK-8实验检测下调PERK表达后结肠癌细胞对化疗药物5-FU的敏感性变化；Annexin V-FITC凋亡实验检测下调PERK表达对结肠癌细胞凋亡的影响；利用RT-PCR及Western Blot实验检测PERK信号通路中关键分子eIF2α、ATF4、CHOP、XIAP的mRNA及蛋白表达变化。结果:RT-PCR实验表明:与正常对照组相比，si-PERK 组mRNA的表达显著下降（P＜0.05）,免疫荧光提示转染效率达80%以上；CCK-8实验发现与si-NC组相比，5-FU对 si-PERK组细胞的半数抑制浓度（IC50）明显降低（P＜0.01）；Annexin V-FITC凋亡实验发现与si-NC组相比，si-PERK组细胞的凋亡发生率显著升高（P＜0.05）；RT-PCR及Western Blot实验发现与si-NC组相比，si-PERK组细胞中PERK信号通路下游关键分子eIF2α、ATF4、CHOP的mRNA及蛋白表达均明显降低（P＜0.05）。结论:在结肠癌细胞中，抑制PERK表达后，其可能通过下调eIF2α、ATF4、CHOP的表达促进细胞发生凋亡，从而促进细胞对化疗药物5-FU的敏感性。     

Preoperative intra-arterial chemotherapy with docetaxel,cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil for oral squamous cell carcinoma

The objectives of this study were to evaluate survival in 141 patients with stage II–IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.     

Recomendaciones sobre el manejo clínico de la infección por el «nuevo coronavirus» SARS-CoV2. Grupo de trabajo de la Asociación Española de Pediatría (AEP)

On 31 December 2019, the Wuhan Municipal Committee of Health and Healthcare (Hubei Province, China) reported that there were 27 cases of pneumonia of unknown origin with symptoms starting on the 8 December. There were 7 serious cases with common exposure in market with shellfish, fish, and live animals, in the city of Wuhan. On 7 January 2020, the Chinese authorities identified that the agent causing the outbreak was a new type of virus of the Coronaviridae family, temporarily called «new coronavirus», 2019-nCoV. On January 30th, 2020, the World Health Organisation (WHO) declared the outbreak an International Emergency. On 11 February 2020 the WHO assigned it the name of SARS-CoV2 and COVID-19 (SARS-CoV2 and COVID-19).The Ministry of Health summoned the Specialties Societies to prepare a clinical protocol for the management of COVID-19. The Spanish Paediatric Association appointed a Working Group of the Societies of Paediatric Infectious Diseases and Paediatric Intensive Care to prepare the present recommendations with the evidence available at the time of preparing them.     

苯扎贝特治疗儿童ApoE Tokyo(Arg25Cys)突变型脂蛋白肾病1例

脂蛋白肾病(Lipoprotein glomerulopathy,LPG),1989年首次由日本学者Saito报道,LPG主要累及肾脏,且以肾小球病变为主[1]。几乎所有患者均有不同程度的蛋白尿,多数表现为肾病综合征,少数表现为轻微蛋白尿和镜下血尿,部分患者伴有不同程度的贫血及高血压,血脂异常易被忽略为肾病综合征的低蛋白血症所致。载脂蛋白E(apolipoprotein E,ApoE)增高是LPG血脂改变的主要特点[2-3]。LPG为一种与脂质代谢紊乱密切相关的肾脏疾病,目前世界范围内有报道的病例不足200例,儿童报道仅10余例[2]。本病进展缓慢,临床常误诊为原发性肾病综合征[4]。因此,为增强对LPG的认识,提高诊治水平,现分析1例确诊的儿童LPG临床资料,总结LPG的临床特点、诊断、治疗及预后。     

肝细胞癌中miR-942-5p的表达及其与患者恶性特征及不良预后的关系

目的:探讨微小RNA-942-5p(miR-942-5p)在肝细胞癌(HCC)组织中的表达及其功能。方法:用实时定量PCR检测西安交通大学第一附属医院样本库保存的73例HCC组织和对应癌旁组织中miR-942-5p的表达。分析miR-942-5p表达与HCC患者临床病理资料的关系,同时分析TCGA数据库中miR-942-5p表达与HCC患者总生存率的关系。Transwell小室检测干扰miR-942-5p表达后HCC细胞迁移和侵袭能力的变化,StarBase V3.0网站和荧光素酶报告基因质粒预测分析miR-942-5p的下游靶点,并用Western blot验证。结果:miR-942-5p表达量在HCC组织中明显高于对应癌旁组织(2.390 vs. 1.764,P0.05)。miR-942-5p表达量与HCC患者肿瘤数目、血管浸润和临床分期明显有关(均P0.05)。miR-942-5p高表达HCC患者总生存率明显低于miR-942-5p低表达HCC患者(19.535%vs. 53.873%,P0.05)。沉默miR-942-5p表达后,肝癌HCCLM3和MHCC97H细胞迁移和侵袭能力明显减弱(均P0.05)。预测与分析结果显示,扣针蛋白5(FBLN5)是miR-942-5p的直接下游靶点(P0.05),沉默miR-942-5p表达导致HCCLM3和MHCC97H细胞中FBLN5表达增加。结论:miR-942-5p在HCC组织中表达异常升高并与恶性临床特征和不良预后密切相关,机制可能与miR-942-5p抑制FBLN5表达促进HCC细胞迁移和侵袭有关。     

Utility of QuantiFERON®-TB Gold In-Tube Test Compared with Tuberculin Skin Test in Diagnosing Tuberculosis in Indian Children with Malnutrition

This prospective cohort study was conducted to compare the accuracy of QuantiFERON®-TB (QFT) Gold In-Tube test and tuberculin skin test (TST) in diagnosing tuberculosis (TB) in predominantly bacille Calmette–Guerin-vaccinated children with a high incidence of malnutrition. The sensitivity of the QFT versus the TST was 69.6% versus 52.9% for WHO-defined TB, with specificity of 86% versus 78.3%, respectively. The concordance of the TST and QFT was 79% overall (κ = 0.430), 62.5% in those with WHO-defined TB and 85.7% in those without TB. Majority of the QFT+/TST − discordance was seen in children with TB, whereas majority of the TST+/QFT − discordance was seen in those without TB. The TST was more likely to be negative in children with moderate-to-severe malnutrition (P = 0.003) compared to the QFT, which was more likely to be positive in younger children. The significantly better performance of the QFT in malnourished children and those at younger ages supports its use for TB diagnosis in these subpopulations.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

Association of regional socioeconomic deprivation and rurality with global developmental delay in early childhood: Data from mandatory school entry examinations in Germany

BackgroundFrom birth to young adulthood, health and development of young people are strongly linked to their living situation, including their family’s socioeconomic position (SEP) and living environment. The impact of regional characteristics on development in early childhood beyond family SEP has been rarely investigated. This study aimed to identify regional predictors of global developmental delay at school entry taking family SEP into consideration.MethodWe used representative, population-based data from mandatory school entry examinations of the German federal state of Brandenburg in 2018/2019 with n=22,801 preschool children. By applying binary multilevel models, we hierarchically analyzed the effect of regional deprivation defined by the German Index of Socioeconomic Deprivation (GISD) and rurality operationalized as inverted population density of the children’s school district on global developmental delay (GDD) while adjusting for family SEP (low, medium and high).ResultsFamily SEP was significantly and strongly linked to GDD. Children with the highest family SEP showed a lower odds for GDD compared to a medium SEP (female: OR=4.26, male: OR=3.46) and low SEP (female: OR=16.58, male: OR=12.79). Furthermore, we discovered a smaller, but additional and independent effect of regional socioeconomic deprivation on GDD, with a higher odds for children from a more deprived school district (female: OR=1.35, male: OR=1.20). However, rurality did not show a significant link to GDD in preschool children beyond family SEP and regional deprivation.ConclusionFamily SEP and regional deprivation are risk factors for child development and of particular interest to promote health of children in early childhood and over the life course.     

Egg Intake Has No Adverse Association With Blood Lipids Or Glucose In Adolescent Girls

Objective: Longitudinal data on cardiometabolic effects of egg intake during adolescence are lacking. The current analyses aim to evaluate the impact of usual adolescent egg consumption on lipid levels, fasting glucose, and insulin resistance during late adolescence (age 17–20?years).

Methods: Data from 1392 girls, aged 9 to 10 at baseline and followed for 10?years, in the National Heart, Lung, and Blood Institute’s National Growth and Health Study were used to examine the association between usual egg intake alone and in combination with other healthy lifestyle factors and late adolescent lipid levels, fasting glucose, and insulin resistance, measured as homeostasis model assessment of insulin resistance (HOMA-IR). Diet was assessed using 3-day food records during eight examination cycles. Girls were classified according to usual weekly egg intake, ages 9–17?years:?<1 egg/wk (n?=?361), 1 to <3 eggs/wk (n?=?703), and ≥3 eggs/wk (n?=?328). Analysis of covariance modeling was used to control for confounding by other behavioral and biological risk factors.

Results: Girls with low, moderate, and high egg intakes had adjusted low-density lipoprotein cholesterol levels of 99.7, 98.8, and 95.5 mg/dL, respectively (p?=?0.0778). In combination with higher intakes of fiber, dairy, or fruits and vegetables, these beneficial effects were stronger and statistically significant. There was no evidence that ≥3 eggs/wk had an adverse effect on lipids, glucose, or HOMA-IR. More active girls who consumed ≥3 eggs/wk had the lowest levels of insulin resistance.

Conclusion: These results suggest that eggs may be included as part of a healthy adolescent diet without adverse effects on glucose, lipid levels, or insulin resistance.     

南充市社区中老年人群血脂血糖现状水平分析

【摘要】 目的 了解社区中老年人群的血脂、血糖现状水平，探讨其与性别和年龄的关系，为本地区心脑血管疾病、糖尿病等疾病的防治提供诊疗依据。方法 对我市38078名社区居民采集清晨空腹血清标本，检测血糖（GLU）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL C）和低密度脂蛋白胆固醇（LDL C）的结果，并对其进行年龄、性别分组统计分析。结果 不同性别和年龄组间的血脂、血糖水平差异有统计学意义（P＜005），74~89岁年龄组血脂、血糖总体水平高于其他各年龄组（P＜005）；女性血脂水平普遍高于男性（P＜005）。结论 中老年人群血脂、血糖异常率高，应定期对中老年人进行血脂、血糖监测，开展宣传教育活动，提高自我保健意识，预防高血脂、高血糖的发生和发展。