Interleukin-11 Overexpression and M2 Macrophage Density are Associated with Angiogenic Activity in Proliferative Diabetic Retinopathy

ABSTRACT

Purpose

To investigate the expression of IL-11 and its receptor IL-11Rα and to quantify density of CD163⁺ M2 macrophages in proliferative diabetic retinopathy (PDR).     

CD44基因多态性与宫颈癌及非小细胞肺癌的相关性

背景与目的：CD44分子是众多肿瘤细胞的标志分子，其表达水平与肿瘤细胞的恶性程度有关。该研究探讨CD44基因中的单核苷酸多态性（single nucleotide polymorphism，SNP）位点与云南汉族人群宫颈癌和非小细胞肺癌（nonsmall cell lung cancer，NSCLC）易感性的相关性。方法：选取了CD44基因中的两个SNP位点rs13347和rs8193，采用TagMan基因分型的方法，分析这两个多态性位点在497例宫颈癌患者和500例健康对照个体以及483例NSCLC患者和471例健康对照个体中的分布特征，并分析CD44基因中的多态性位点与云南汉族人群宫颈癌和NSCLC的相关性。结果：rs13347和rs8193位点等位基因和基因型在宫颈癌组和对照组中的分布频率的差异无统计学意义（P>0.05）。而在NSCLC组和对照组的比较中：rs13347和rs8193位点等位基因在NSCLC组和对照组中的分布频率的差异有统计学意义（P=0.020和P=0.004）；这两个位点基因型在NSCLC组和对照组中分布频率的差异有统计学意义（P=0.027和P=0.020）；其中rs13347位点等位基因C在NSCLC组中的分布频率显著高于对照组，可能是NSCLC发生的风险因素（OR=1.250，95% CI：1.035～1.509），rs8193位点等位基因C在对照组中的分布频率显著高于NSCLC组，可能是NSCLC发生的保护性因素（OR=0.768，95%CI：0.641～0.921）。单倍型分析结果显示，rs13347C-rs8193T和rs13347T-rs8193C在NSCLC组和对照组中的分布频率差异有统计学意义（P=0.003和0.022）；该结果说明单倍型rs13347C-rs8193T可能是云南汉族人群NSCLC发生的风险性因素（OR=1.316，95%CI：1.096～1.579）。结论：CD44基因中的两个SNP位点rs13347和rs8193可能与云南汉族人群宫颈癌发病风险无关，而可能与云南汉族人群NSCLC具有相关性。     

Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44+ cancer stem cells

Cis-diamminedichloridoplatinum(II)(CDDP)-based combination chemotherapy is frequently used in gastrointestinal cancer. The synergistic mechanism of all-trans retinoic acid (ATRA), cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear. Despite their potent antitumor properties, resistance to CDDP and 5-FU develops frequently in tumors. To clarify this mechanism, we determined the sensitivity to each drug and their combination in two gastrointestinal cancer stem cells (CSCs) subpopulation.Here, we report the identification and separation of CD44⁺ cells from human gastric carcinoma (AGS) and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines by magnetic activated cell sorting (MACS). We allowed the CD44^± cells to grow 6 days at a subtoxic concentration of ATRA and then treated with different concentration of CDDP and 5-FU for 24 h. The cytotoxicity was examined by cell proliferation MTT assay. Additionally, AO/EB staining was used for detection of apoptotic cells. In order to determine whether the growth inhibition was also associated with changes in cell cycle distribution, cell cycle analysis was performed using flow cytometry.Low concentration of ATRA (1 μM, 6days) followed by 5-FU and CDDP was found to be more effective than either drugs alone, thus resulting in synergistic cytotoxicity in Kyse-30 and AGSCD44^± cells. Furthermore, there was an indication that the combination of ATRA with 5FU and CDDP caused an increase in cell cycle arrest in G2/M and G0/G1.We conclude that low concentration of ATRA enhances the cytotoxicity of CDDP and 5FU by facilitating apoptosis and cell cycle arrest in gastrointestinal CSCs and provide a rational basis for the design of novel, well-tolerated CDDP- and 5FU-based chemotherapy in human gastrointestinal carcinoma.     

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

1. Download : Download high-res image (134KB)
2. Download : Download full-size image

     

Left Ventricular Systolic Dysfunction and Cardiovascular Outcomes in Tetralogy of Fallot: Systematic Review and Meta-analysis

BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem.     

喉癌患者PAC-1、CD62P表达与临床病理特征和复发的关系

目的探讨喉癌患者血小板表面血小板膜糖蛋白Ⅱb/Ⅲa纤维蛋白原受体(PAC-1)、血小板P-选择素(CD62P)阳性表达率以及与患者临床病理特征和复发的关系。方法选取2014年1月~2015年12月间在我院耳鼻喉科手术治疗的116例喉癌患者,随访≥2年,并选取同期在我院体检的健康人群60例为对照组,采用流式细胞仪检测法检测外周血PAC-1和CD62P阳性率,并分析与临床病理特征、复发的关系。结果喉癌患者PAC-1和CD62P阳性表达率分别为(17.82±1.76)%和(22.87±3.13)%,明显高于健康人群(P<0.05);而且在喉癌患者PAC-1表达和CD62P表达呈正相关性(r=0.238,P<0.05)。T3-T4分期或N2-N3分期患者PAC-1和CD62P阳性表达率高于T1-T2分期或N0-N1分期患者(P<0.05)。另外远处转移组PAC-1和CD62P阳性表达率高于未发生转移组(P<0.05);随访期间有24例患者复发,复发率为20.69%。复发喉癌患者PAC-1、CD62P阳性表达率分别为(17.02±0.85)%和(21.84±1.17)%,明显高于未复发的喉癌患者(P<0.05)。经Logistics回归分析,PAC-1和CD62P是喉癌患者复发的独立危险因素(P<0.05)。结论PAC-1和CD62P阳性表达率与喉癌患者T分期、淋巴结转移和远处转移密切相关,同时可作为喉癌局部复发、区域淋巴结转移、远处转移的预测指标。     

Implementation of Recommendations for Long-Acting Contraception Among Women Aged 13 to 18 Years in Primary Care

ObjectiveClinical specialty societies recommend long-acting reversible contraceptives (LARCs) as first-line contraception for adolescent women. We evaluated whether a combined educational and process improvement intervention enhanced LARC placement in primary care within an integrated health care system.MethodsThe intervention included journal clubs, live continuing education, point-of-care guidelines, and new patient materials. We conducted a retrospective cohort study across 3 time periods: baseline (January 2013?September 2015), early implementation (October 2015–March 2016), and full implementation (April 2016–June 2017). The primary outcome was the proportion of LARCs placed by primary care clinicians among women aged 13 to 18 years compared with gynecology clinicians.ResultsKaiser Foundation Health Plan of Colorado cared for approximately 20,000 women aged 13 to 18 years in each calendar quarter between 2013 and 2017. Overall, LARC placement increased from 7.0 per 1000 members per quarter at baseline to 13.0 per 1000 during the full intervention. Primary care clinicians placed 6.2% of all LARCs in 2013, increasing to 32.1% by 2017 (P < .001), including 45.5% of contraceptive implants. Clinicians who attended educational sessions were more likely to adopt LARCs than those who did not (17.9% vs 6.4% respectively, P = .009). Neither overall LARC placement rates (relative risk, 1.9; 95% confidence interval, 0.7?5.6) nor contraceptive implant rates (relative risk, 3.0; 95% confidence interval, 0.9?9.8) increased significantly in clinicians who attended educational activities.ConclusionsThis multimodal intervention was associated with increased LARC placement for adolescent women in primary care. The combination of education and process improvement is a promising strategy to promote clinician behavior change.     

AAV-CRISPR Gene Editing Is Negated by Pre-existing Immunity to Cas9

1. Download : Download high-res image (155KB)
2. Download : Download full-size image