视网膜新生血管的药物治疗研究进展

全身或局部的病变可导致血—视网膜屏障破坏、血液微循环障碍和血管通透性改变,进一步引起视网膜缺氧,乃至水肿,随之视网膜组织对缺氧发生一系列代偿性反应,在各种细胞因子、细胞内外调控机制的共同作用下生成新生血管,目的是补偿缺血缺氧的视网膜。视网膜新生血管相关疾病包括糖尿病性视网膜病变、视网膜静脉周围炎、早产儿视网膜病变等。抑制新生血管生长是治疗这类疾病的关键。本文对抑制视网膜新生血管药物的研究进展作一综述。     

小鼠视网膜新生血管模型的建立及特征

目的:建立可靠稳定的视网膜新生血管动物模型,为今后探究视网膜新生血管疾病的发生机制和治疗方法奠定模型基础。方法:将24只新生C57BL/6J小鼠随机分为正常组和模型组,每组各12只。将模型组小鼠于生后第7d置于750mL/L氧浓度环境,生后第12d返回正常空气中;正常组小鼠始终置于正常空气环境喂养。至小鼠生后第17d进行心脏荧光素灌注造影视网膜铺片以及眼球连续切片苏木精-伊红(H-E)染色,观测视网膜新生血管生成情况。结果:模型组小鼠心脏荧光素灌注造影结果显示视网膜中央区域呈无灌注缺血,另外视网膜血管有迂曲扩张、荧光渗漏等异常表现。眼球连续切片发现模型组小鼠突出视网膜内界膜的血管内皮细胞核数为48.65±6.24个/片/眼,而正常组小鼠平均为0.38±0.21个/片/眼,两组比较差异有显著统计学意义(P<0.01)。结论:氧诱导的视网膜缺血模型可成功诱导小鼠产生视网膜新生血管,可作为探究视网膜新生血管疾病发生机制和治疗方法的可靠动物模型。     

基于全脑影像组学的阿尔茨海默病诊断研究

目的：探讨构建影像组学、临床和联合模型,对正常认知（cognitively normal,CN）组、轻度认知障碍（mild cognitive impairment,MCI）组和阿尔茨海默病（Alzheimer’s disease,AD）组的分类价值。方法：选取阿尔茨海默病神经影像学倡议（Alzheimer’s Disease Neuroimaging Initiative,ADNI）数据库中139例CN、162例MCI和128例AD患者基线的临床和影像资料。以7∶3的比例随机分为训练集和验证集。基于3D-T1WI磁共振成像（magnetic resonance imaging,MRI）提取影像组学特征。在训练集中,使用套索回归算法（least absolute shrinkage and selection operator,LASSO）筛选组学特征,并通过多因素逻辑回归建立基于全脑皮层及皮层下核团的影像组学模型。使用单因素逻辑回归和多因素逻辑回归获得与分类相关的临床指标,并通过多因素逻辑回归模型建立临床模型和基于影像组学特征和临床指标的联合模型。用受试者工作特征（receiver ...     

CT技术诊断下肢动脉硬化闭塞症的应用进展

CT血管成像技术(CTA)在下肢动脉硬化闭塞症诊断中的应用日益广泛。该技术相对其他方法来说具有无创、简便等明显优势。数字减影血管造影以往被认为是诊断动脉硬化性疾病的唯一可靠方法, 而目前CTA技术对这个老的“金标准”提出了挑战。多源CT的应用使全动脉树形结构的无创成像成为可能, 该技术的优化令动脉硬化性疾病的诊断更加精准。对比剂的应用和仪器参数的优化, 使CTA检查的照射剂量明显降低。今后, 随着CT技术的快速发展, CTA技术必将成为诊断下肢动脉闭塞疾病的理想方法。     

膀胱灌注RTX治疗间质性膀胱炎的临床研究

目的:探讨膀胱灌注辣椒辣素类似物(resiniferatoxin,RTX)治疗间质性膀胱炎(interstitial cystitis,IC)的有效性和安全性.方法:56例间质性膀胱炎患者行RTX一次性膀胱灌注治疗.观察用药前及用药后1周、1个月、3个月时患者的临床症状情况(每日排尿次数、最大排尿容量、尿痛程度评分)和O'Leary-Sant问质性膀胱炎问卷表评分及生活质量评分(QOL)情况.并记录不良反应发生情况.结果:①患者用药后1周、1个月、3个月时每日排尿次数明显减少(用药前vs用药后1 W、1 M和3 M的每日排尿次数:28.41±10.77 vs 15.30±4.77、15.63±3.70和17.19±4.06),最大排尿容量增加[用药前vs用药后1 W、1 M和3 M的最大排尿容量为:124.26±79.31 vs 187.41±67.46、188.89±62.35和161.85±65.11(ml)],疼痛程度评分明显下降(用药前vs用药后1 W、1 M和3 M的疼痛程度评分为:6.74±1.38 vs 3.89±1.15、4.63±1.31和4.85±1.67),与用药前相比,差异具有统计学意义.②患者用药后1周、1个月、3个月时O'Leary-Sant评分和生活质量评分与用药前相比(O'Leary-Sant评分:用药前vs用药后1 W,1 M,3 M为27.93±4.03 vs 28.04±6.69,27.44±3.89,27.96±4.13;生活质量评分:用药前vs用药后1 W、1 M、3 M为5.52±0.51 vs 5.30±0.47、5.33±0.56、5.44±0.51),比较差异无统计学意义.③所有患者均坚持完成试验,无一例退出.使用RTX后患者生命体征均平稳,其中20例有轻度或中度膀胱或尿道刺激症状,可以耐受,1～3天后均自行消失,无全身不良反应.结论:用RTX膀胱灌注治疗能有效缓解间质性膀胱炎的临床症状和改善其生活质量,且耐受性及安全性好.     

GDF15在肾移植缺血-再灌注损伤中的作用及机制研究

目的  探讨生长与分化因子（GDF）15在肾移植缺血-再灌注损伤（IRI）中的作用及机制。方法  选取野生型供体小鼠9只,野生型受体小鼠9只,分别于术后4、24、72 h取3只受体小鼠的移植肾,进行GDF家族转录组学分析,检测各组肾组织GDF15的表达情况。选取野生型供体小鼠5只,GDF15敲除型供体小鼠5只,野生型受体小鼠10只,根据实验方案将小鼠分为野生型假手术组、野生型移植组、GDF15敲除假手术组、GDF15敲除移植组,于术后72 h提取血清及肾组织样本,对比各组肾功能、肾小管损伤情况、炎症细胞浸润、炎症因子及Toll样受体4（TLR4）、核因子（NF）-κB表达水平。选取野生型供体小鼠9只,GDF15敲除型供体小鼠9只,野生型受体小鼠18只,根据实验方案将小鼠分为野生型移植组、GDF15敲除移植组,观察肾移植术后两组生存率。结果  GDF15是移植肾转录组学中上调最多的GDF家族基因,主要在肾小管中表达。与假手术组比较,移植组小鼠肾功能下降;与野生型移植组比较,GDF15敲除移植组小鼠血清肌酐、血尿素氮水平升高（均为P < 0.05）。野生型移植组小鼠术后1周生存率为87.6%,GDF15敲除移植组小鼠术后1周生存率为41.8%。GDF15敲除移植组肾损伤分子（KIM）-1表达增多,肾小管损伤评分更高。野生型移植组肾小管可见溶解或坏死,髓外和皮质中可见管型形成,而GDF15敲除移植组肾小管坏死及管型更加明显。移植组髓过氧化物酶（MPO）和F4/80表达增多,且GDF15敲除移植组炎症细胞浸润加重。与假手术组比较,移植组肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和IL-6表达水平升高;与野生型移植组比较,GDF15敲除移植组TNF-α、IL-1β和IL-6表达水平升高（均为P < 0.05）。移植组肾组织中TLR4、NF-κB表达较假手术组增多;GDF15敲除移植组肾组织中TLR4和NF-κB表达较野生型移植组增多。结论  GDF15可减轻移植肾IRI,其作用机制可能与抑制TLR4-NF-κB信号通路有关。     

Architectural analysis of subconjunctival oblique limbus incision techniques in manual cataract extraction surgery by optical coherence tomography imaging

The purpose was to assess the profile of subconjunctival oblique limbus incision (SCOLI) design by using anterior-segment optical coherence tomography (AS-OCT) and try to emphasize the proper technique of wound construction. The structural dimensions and integrity of the wound were acquired from the patients, who had undergone manual small-incision cataract surgery with SCOLI techniques, using a Canon OCT anterior-segment imaging system on the first postoperative day. The use of AS-OCT allowed for an in vivo evaluation of SCOLI in high definition. The radial OCT scan image showed three staggered incisions, including conjunctiva incision, scleral entrance, and inner corneal lip. A tangential scan demonstrated that the internal lip is parallel to the curvature of the peripheral cornea. The en face image showed an asymmetric 4 arc-shaped configuration rather than a symmetrical one. In conclusion, AS-OCT could be used to analyze SCOLI to determine optimal wound construction and geometry. The results of this study indicated that an asymmetric 4 arc-shaped limbus tunnel incision was superior to the conventional linear equivalent in stability and nucleus delivery.     

维生素D改善2型糖尿病相关机制研究进展

2型糖尿病（T2DM）的病因和发病机制目前尚未完全阐明,但是从糖脂毒性到炎症学说,人们对其认识正逐步深化;维生素D的传统作用表现在调节钙磷代谢和促进骨质形成,随着多种细胞内1,25（OH）₂D₃受体的发现,维生素D在降低肿瘤、糖尿病、心血管疾病和肥胖等慢性疾病危险方面的作用正日益成为研究者们关注的焦点;本文将对维生素D在胰岛β细胞功能缺陷、胰岛素抵抗、免疫和炎症调节中的作用予以综述,重点介绍维生素D与T2DM相互关系的生理学机制,并从维生素D受体基因多态性方面解释人群实验中补充维生素D对2型糖尿病防治效果差异性产生的原因。     

Use of specific contrast-enhanced CT regions of interest to differentiate renal oncocytomas from small clear cell and chromophobe renal cell carcinomas

PURPOSEWe aimed to examine the usefulness of utilizing a specific contrast-enhanced computed tomography (CT) region of interest (ROI) to differentiate renal oncocytoma (RO) from small clear cell renal cell carcinoma (ccRCC) and chromophobe renal cell carcinoma (chRCC).METHODSA retrospective analysis of pre-contrast phase (PCP), corticomedullary phase (CMP), and nephro­graphic phase (NP) contrast-enhanced CT images of the histopathologically confirmed initial cohort (27 ROs, 74 ccRCCs, and 36 chRCCs) was conducted. Small, medium, large, and whole ROIs (S-ROI, M-ROI, L-ROI, and W-ROI, respectively) were utilized for CT attenuation value of tumor (AVT), lesion-to-cortex attenuation (L/C), and heterogeneous degree of tumor (HDT) calculations. Differences in these parameters were then compared between RO and ccRCC/chRCC, with receiver operating characteristic (ROC) curves being utilized to gauge the diagnostic utility of the statistically significant parameters. Logistic regression analyses were employed to identify key factors capable of differentiating RO and ccRCC/chRCC, with predictive models further being established. A validation cohort (6 ROs, 30 ccRCCs, and 12 chRCCs) was then employed to validate the performance of the predictive models.RESULTSOf the parameters evaluated using different ROIs, L/C-CMP (S-ROI) (0.88 ± 0.15 vs. 1.13 ± 0.25, P < .001) and HDT-CMP (W-ROI) (23.02 (12.00-51.21) vs. 37.81 (16.09-89.45), P < .001) were best suited to differentiating RO and ccRCC, yielding respective area under the curve (AUC) values of 0.803 and 0.834. AVT-NP (S-ROI) (122.85 ± 18.87 vs. 86.50 ± 18.65, P < .001) and AVT-NP (M-ROI) (119 (86-167) vs. 81.5 (53-142), P < .001) were better able to differentiate RO and chRCC, yielding respective AUC values of 0.918 and 0.906. Logistic regression analyses revealed that L/C-CMP (S-ROI) and HDT-PCP, as well as AVT-NP (S-ROI) and HDT-CMP, were the primary factors capable of differentiating RO from ccRCC and chRCC, respectively. The predictive model developed to differentiate between RO and ccRCC exhibited a sensitivity of 66.67% and 55.14% in the initial and validation cohorts, respectively, with corresponding specificity of 94.59% and 93.55%, accuracy of 87.13% and 86.84%, and AUC of 0.908 and 0.876. The predictive model developed to differentiate between RO and chRCC exhibited a sensitivity of 85.19% and 100.00% in the initial and validation cohorts, respectively, with corresponding specificity of 94.59% and 92.86%, accuracy of 87.30% and 95.24%, and AUC of 0.944 and 0.959.CONCLUSIONThese data demonstrate that a combination of quantitative parameters measured with particular ROIs can enable the efficient and reliable differentiation of RO from ccRCC and chRCC for use in routine patient differential diagnosis.

Main points

• Quantitative computed tomography (CT) parameters measured using different regions of interest (ROIs) exhibit varying levels of diagnostic efficacy when differentiating renal oncocytoma (ROs) from small clear cell renal cell carcinomas (ccRCCs) and chromophobe renal cell carcinomas (chRCCs).
• Lesion-to-cortex attenuation- corticomedullary phase (CMP) (small ROI (S-ROI)) and attenuation value of the tumor-nephrographic phase (S-ROI) were identified as the most reliable enhancement degree-related quantitative parameters when distinguishing ROs from ccRCCs and chRCCs, respectively.
• Heterogeneous degree of tumor (HDT), which was defined based upon the standard deviation for CT values, can serve as a quantitative measure of heterogeneity when differentiating ROs from ccRCCs and chRCCs, with HDT-CMP exhibiting the highest degree of differential diagnostic efficacy.
• Predictive models combining the above S-ROI-based enhancement degree parameters and whole ROI-based HDT values exhibit excellent diagnostic efficacy when differentiating ROs from ccRCCs and chRCCs.

An estimated 20%-30% of solid masses < 4 cm in size are benign, with renal oncocytomas (ROs) accounting for over half of these cases while the remaining 70%-80% are renal cell carcinomas (RCCs), among which clear cell RCCs (ccRCCs) are the most prevalent, followed by papillary RCCs (pRCCs) and chromophobe RCCs (chRCCs).^1,2 Given that ROs exhibit a benign disease course and affected patients have an excellent prognosis, accurately differentiating between RO and RCC is critical to guide appropriate patient treatment.³Computed tomography (CT) is the most common approach used for the diagnosis and evaluation of renal masses. Several reports have described the differentiation between ROs and RCCs based upon both qualitative and quantitative CT findings, with the enhancement degree and heterogeneity being 2 key indicators.^4-8 Owing to a lack of reference standard uniformity, however, these studies utilized different approaches to define the regions of interest (ROIs) to obtain CT parameter values, potentially contributing to inconsistencies or opposing findings among studies. Also, tumor heterogeneity is also considered to be a largely subjective determination of limited clinical utility.^7-8 Rosenkrantz et al.⁹ found the use of a small ROI (S-ROI) to be more accurate than a large ROI (L-ROI) when differentiating between RCCs and cysts, with this approach being most effective when comparing pRCCs and cysts. Wang et al.¹⁰ also reported that S-ROI-based enhancement degree and whole ROI (W-ROI)-based enhancement heterogeneity were superior to medium ROI (M-ROI) when differentiating between small ccRCC and fat-poor angiomyolipoma (AML).To date, no studies have explored the use of different ROIs to differentiate between ROs and RCCs on contrast-enhanced CT images. Given that pRCCs are typically hypovascular, efforts to distinguish between ROs and RCCs are generally focused on the chRCCs and ccRCCs.^11-12 This study was thus developed to explore the effect of ROI size in differentiating ROs from ccRCCs and chRCCs in an effort to define the most effective quantitative parameters for routine differential diagnosis.