AA

AA
  • 文章类型: Letter
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:氧化应激(OS)在白癜风和斑秃(AA)中的具体作用尚不清楚。本研究的目的是通过生物信息学分析和鉴定白癜风和AA中OS的关键标志物。
    方法:我们从基因表达综合(GEO)数据库获得了白癜风和AA数据集。通过差异分析鉴定白癜风和AA的差异表达基因。并通过基因本体论(GO)鉴定差异表达基因的功能,京都基因和基因组百科全书(KEGG),和基因集富集分析(GSEA)富集分析。随后,采用Veen软件包获取OS相关基因与白癜风和AA的交集基因。最后,我们使用CIBERSORT评估白癜风和AA的免疫细胞浸润。
    结果:通过富集分析,我们发现白癜风和AA主要富集在细胞周期和细胞粘附分子通道。我们确定KLB和EIF3C是白癜风和AA的OS调控的关键基因。发现KLB和EIF3C通过调节T细胞和中性粒细胞参与疾病进展。
    结论:根据我们的发现,KLB和EIF3C在白癜风和AA的进展和发展中起着至关重要的作用。已被确定为生物标志物和目标,用于患者的早期诊断。
    BACKGROUND: The specific role of oxidative stress (OS) in vitiligo and alopecia areata (AA) remains unclear. The aim of this study was to analyze and identify the key markers of OS in vitiligo and AA by bioinformatics.
    METHODS: We obtained vitiligo and AA datasets from gene expression omnibus (GEO) database. The difference-expressed genes of vitiligo and AA were identified by differential analysis, and the functions of difference-expressed genes were identified by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis. Subsequently, Veen package was used to obtain the intersection genes of OS-related genes with vitiligo and AA. Finally, we used CIBERSORT to assess the infiltration of immune cells in vitiligo and AA.
    RESULTS: Through enrichment analysis, we found that vitiligo and AA were mainly enriched in cell cycle and cell adhesion molecular channels. We identified KLB and EIF3C as key genes in OS regulation of vitiligo and AA, and found that KLB and EIF3C participate in disease progression by regulating T cells and neutrophils.
    CONCLUSIONS: According to our findings, KLB and EIF3C play a crucial role in the progression and development of vitiligo and AA, which have been identified as biomarkers and target for early diagnosis of patients.
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  • 文章类型: Journal Article
    高活性抗逆转录病毒疗法(HAART)的引入导致发达国家和发展中国家中与人类免疫缺陷病毒(HIV)相关的发病率和死亡率的显著降低。虽然HAART已有效减少快速进行性视网膜病变,艾滋病毒的其他眼部表现尚待确定,表征和解决。该研究的目的是确定HAART对西北地区HIV/AIDS患者的调节-融合机制的影响。尼日利亚。
    这是基于医院的队列研究,于2019年4月至2019年11月进行。招募符合纳入标准的参与者,将其分为A组和B两组。而B组被细分为四组;由B1组成:那些已经接受HAART治疗0-2½年的患者,B2组:>2½-5年,B3组:>5-7½年,和B4组:>7½-10年,称为HAART体验。从患者那里获得的信息包括性别,年龄,婚姻状况,近收敛点(NPC),住宿幅度(AA),老花眼阅读添加(ADD),CD4+T细胞计数,HAART方案和HAART治疗的持续时间。
    有400名参与者,年龄在25-55岁之间,平均年龄为37.86±7.5岁。参与者的NPC平均值为6.4±1.47cm,范围为2-18cm。与具有正常NPC值的64(16%)相比,大多数参与者336(84.0%)具有异常近点收敛。平均AA为4.18±1.34DS,范围为0.75至10.0DS,约273名(68.2%)参与者的AA在3至5DS之间。平均老花眼添加量为1.39±0.98DS,范围为1.00至3.50DS,而大多数参与者,305(76.2%)的阅读增加异常。
    研究表明,接受HAART的HIV/AIDS患者表现出异常低的AA,与年龄匹配的HAART天真相比,NPC和老花眼读数增加减少。AA和HAART(p=0.002)与HAART持续时间(p=0.00)之间存在统计学上的显着关联,但与他们的CD4+T细胞水平和HAART方案无关(p=0.12,p=0.08).异常阅读添加与HAART之间没有统计学上的显着关联(p=0.46),CD4+4T细胞水平和HAART方案(p=0.53和p=0.59),但与HAART持续时间有统计学显著关联(p=0.00).
    UNASSIGNED: The introduction of Highly Active Anti-Retroviral Therapy (HAART) has led to a dramatic decrease in Human Immune Deficiency Virus (HIV) related morbidity and mortality in the developed as well as developing world. Whilst HAART has been effective in reducing rapidly progressive retinopathies, there are other ocular manifestations of HIV which are yet to be determined, characterised and addressed. The aim of the study was to determine the effect of HAART on Accommodative-Convergence mechanism among HIV/AIDS patients in Northwestern, Nigeria.
    UNASSIGNED: This was hospital-based cohort study carried out from April 2019 to November 2019. Participants that met the inclusion criteria were recruited and were separated into two groups A and B. Group A were those about to commence HAART referred to as HAART naive, while group B were subdivided into four groups; comprising of B1: those that had been on HAART for 0 - 2½ years, group B2: >2½ - 5 years, group B3: >5 - 7½ years, and group B4: >7½ - 10 years, termed as HAART experience. Information obtained from the patients included sex, age, marital status, Near Point of Convergence (NPC), Amplitude of Accommodation (AA), Presbyopic reading Addition (ADD), CD4+ T cell count, HAART regimen and duration on HAART therapy.
    UNASSIGNED: There were 400 participants aged 25 - 55years with a mean age of 37.86 ± 7.5years. The participant\'s NPC mean was 6.4 ± 1.47cm with a range of 2 - 18cm. Most of the participants 336 (84.0%) had an abnormal Near Point of Convergence compared to 64 (16%) with normal NPC values. The mean AA was 4.18± 1.34DS, ranging from 0.75 to 10.0DS and about 273 (68.2%) of the participant\'s AA was within 3 to 5DS. The mean presbyopic addition was 1.39± 0.98 DS ranging from 1.00 to 3.50DS whilst majority of the participants, 305 (76.2%) had an abnormal Reading Addition.
    UNASSIGNED: The study showed that the HIV/AIDS patients on HAART exhibit an abnormally low AA, receded NPC and High presbyopic reading addition as compared to age matched HAART naïve. There was a statistically significant association between AA and HAART (p = 0.002) and HAART duration (p = 0.00), but there was no association with their CD4+ T cell levels and HAART regimen (p = 0.12, p = 0.08). There was no statistically significant association between Abnormal reading addition and HAART (p= 0.46), CD4+4 T cell levels and HAART regimen (p=0.53 and p= 0.59), but there was a statistically significant association with HAART duration (p= 0.00).
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  • 文章类型: Case Reports
    再生障碍性贫血是一种罕见的血液系统疾病,其特征是造血功能抑制和全血细胞减少。尽管有几种药物与再生障碍性贫血有关,它的发生是对奥希替尼的反应,第三代表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKI),极为罕见。我们提供了一例63岁的局部晚期非小细胞肺癌(NSCLC)患者的病例报告,该患者在接受奥希替尼辅助治疗后发展为再生障碍性贫血。广泛的调查排除了感染性病因,并且没有骨髓受累或其他可识别的原因表明是药物引起的病因,特别是奥希替尼。本病例报告强调认识到这一不良事件并将其视为奥希替尼治疗的潜在并发症的重要性。警惕监测和及时管理对于优化患者预后至关重要。需要进一步的研究来更好地了解风险因素,潜在机制,奥希替尼诱导的再生障碍性贫血的辅助治疗策略.
    Aplastic anemia is a rare hematological disorder characterized by suppressed hematopoiesis and pancytopenia. Although several drugs have been associated with aplastic anemia, its occurrence in response to Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is extremely rare. We present a case report of a 63-year-old patient with locally advanced non-small cell lung cancer (NSCLC) who developed aplastic anemia following adjuvant treatment with Osimertinib. Extensive investigations ruled out infectious etiology, and the absence of bone marrow involvement or other identifiable causes suggested a drug-induced etiology, specifically Osimertinib. This case report emphasizes the importance of recognizing this adverse event and considering it as a potential complication of Osimertinib therapy. Vigilant monitoring and prompt management are essential for optimizing patient outcomes. Further studies are needed to better understand the risk factors, underlying mechanisms, and management strategies for Osimertinib-induced aplastic anemia in the adjuvant settings.
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  • 文章类型: Journal Article
    目的:跟踪测试B部分(TMT-B)评估执行功能,记忆,和感觉运动功能。以前没有研究发现APOE-ε4基因型对阿尔茨海默病(AD)中TMT-B评分的纵向影响。
    方法:这项研究使用了阿尔茨海默病神经影像学倡议(ADNI)的数据:382名患有AD的参与者,503与认知正常(CN),1293例轻度认知障碍(MCI)在基线和随访四年。多变量线性混合模型用于研究APOE-ε4基因型对TMT-B评分变化的影响。
    结果:与白人相比,非洲裔美国人(AA)和西班牙裔美国人的TMT-B得分较高(认知功能较差)。此外,在基线和四次随访时,与没有APOE-ε4等位基因的个体相比,具有1或2个APOE-ε4等位基因的白人受试者的TMT-B得分明显更高;然而,在西班牙裔和AA组中,APOE-ε4等位基因之间的TMT-B没有发现差异。在3个种族群体中未发现通过访问互动的APOE-ε4。按AD诊断分层,APOE-ε4等位基因仅在MCI组中与TMT-B评分相关,虽然教育访问有重要的互动,APOE-ε4等位基因,MCI组的简易精神状态检查(MMSE)评分。此外,TMT-B与MMSE显著相关,AD评估量表-认知子量表13(ADAS13),ttau,pTau,Aβ42和海马。
    结论:APOE-13C4等位基因与白人受试者的TMT-B评分相关,但不是在西班牙裔和AA组。APOE-ε4在MCI组中显示与访问的相互作用。
    OBJECTIVE: The trail making test part B (TMT-B) evaluates executive functions, memory, and sensorimotor functions. No previous study was found to examine the longitudinal effect of APOE-ε4 genotypes on the TMT-B scores in Alzheimer\'s disease (AD) across racial groups.
    METHODS: This study used the data from Alzheimer\'s Disease Neuroimaging Initiative (ADNI): 382 participants with AD, 503 with cognitive normal (CN), 1293 with mild cognitive impairment (MCI) at baseline and follow-up of four years. The multivariable linear mixed model was used to investigate the effect of APOE-ε4 genotypes on changes in TMT-B scores.
    RESULTS: Compared with Whites, African Americans (AA) and Hispanics had higher TMT-B scores (poor cognitive function). Furthermore, Whites subjects with 1 or 2 APOE-ε4 alleles had significantly higher TMT-B scores compared with individuals without APOE-ε4 allele at baseline and four follow-up visits; however, no differences in TMT-B were found between APOE-ε4 alleles in the Hispanic and AA groups. No APOE-ε4 by visit interactions was found for 3 racial groups. Stratified by AD diagnosis, the APOE-ε4 allele was associated with TMT-B scores only in the MCI group, while there were significant interactions for visit by education, APOE-ε4 allele, and the Mini Mental State Examination (MMSE) score in the MCI group. In addition, TMT-B was significantly correlated with the MMSE, AD Assessment Scale-cognitive subscale 13 (ADAS13), tTau, pTau, Aβ42, and hippocampus.
    CONCLUSIONS: APOE-ɛ4 allele is associated with TMT-B scores in Whites subjects, but not in the Hispanic and AA groups. APOE-ε4 showed interaction with visit in the MCI group.
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  • 文章类型: Journal Article
    在这项研究中,5,10,15,20-(4-磺基苯基)卟啉(TPPS4)因其优异的特性包括高量子产率而被选作荧光探针,良好的水溶性,和特殊的生物相容性。激发波长设置为515nm,TPPS4的最佳荧光发射波长为642nm。此时此刻,TPPS4粉红色溶液的荧光信号处于\'ON\'状态。当引入抗坏血酸(AA)时,TPPS4的荧光强度被猝灭,这是由于AA和TPPS4之间的电子转移猝灭作用。相应溶液的颜色从粉红色变为绿色,荧光信号处于“关闭”状态。当将HPO42-进一步引入TPPS4-AA系统时,由于HPO42-与AA之间的独特相互作用,TPPS4的猝灭荧光强度得以恢复。此时,相应溶液的颜色从绿色变为红色,和荧光信号处于\'ON\'状态。因此,基于TPPS4构建了一个“ON-OFF-ON”信号可切换的荧光探针来检测HPO42-。结果表明,HPO42-的线性范围为4.0×10-9~1.7×10-6M,检出限为1.3×10-9M(S/N=3)。传感系统具有很高的精度和灵敏度,它可以成功地检测实际样品中的HPO42-。
    In this study, 5,10,15,20-(4-sulphonatophenyl)porphyrin (TPPS4 ) was selected as a fluorescent probe due to its excellent characteristics including high quantum yield, good water solubility, and exceptional biocompatibility. With an excitation wavelength set at 515 nm, the optimal fluorescence emission wavelength for TPPS4 was measured at 642 nm. At this moment, the fluorescence signal of TPPS4 pink solution was in the \'ON\' state. The fluorescence intensity of TPPS4 was quenched when ascorbic acid (AA) was introduced, which was due to the electron transfer quenching effect between AA and TPPS4 . The colour of the corresponding solution changed from pink to green, and the fluorescence signal was in the \'OFF\' state. When HPO4 2- was further introduced into the TPPS4 -AA system, the quenched fluorescence intensity of TPPS4 was recovered due to the unique interaction between HPO4 2- and AA. At this time, the colour of the corresponding solution changed from green to red, and the fluorescence signal was in the \'ON\' state. Therefore, an \'ON-OFF-ON\' signal-switchable fluorescent probe was constructed based on TPPS4 to detect HPO4 2- . The results showed that the linear range of HPO4 2- was 4.0 × 10-9 to 1.7 × 10-6  M, and the detection limit was 1.3 × 10-9  M (S/N = 3). The sensing system exhibited high accuracy and sensitivity, and it could be used successfully to detect HPO4 2- in real samples.
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  • 文章类型: Journal Article
    目的:确定尿路/前列腺中不同淀粉样蛋白类型的患病率和相关系统性淀粉样变性的频率。
    方法:我们在2008年至2020年期间研究了刚果红阳性前列腺(n=150)和尿路(n=767)标本,采用基于蛋白质组学的方法进行分型。临床随访可用于一个子集(尿路,n=111;前列腺,n=17)。淀粉样蛋白类型与各种临床病理特征相关。对患者进行临床随访,进行图表审查以建立局部疾病与全身性疾病,尿路/前列腺标本上淀粉样变性的初始诊断频率,心脏病的存在,和死于疾病相关并发症。
    结果:最常见的淀粉样蛋白类型是尿路AL/AH(479/767,62%)和前列腺局部ASem1(64/150,43%)。尿路AL/AH淀粉样蛋白通常是局部的,但系统性AL淀粉样变性发生在两个部位(尿路:5/71,7%;前列腺:2/2,100%)。在超过三分之一的病例中观察到ATTR淀粉样变性(尿路:286/767,37%;前列腺:55/150,37%)。尿路/前列腺是44/48例患者(92%)中ATTR淀粉样变性的初始诊断部位,38/48(79%)随后发现心脏受累。精囊/射精管受累是ASem1型淀粉样变性的病因(39/39,100%)。
    结论:超过40%的患者有系统性淀粉样变性,泌尿道/前列腺通常是发现淀粉样蛋白的第一个部位。由于早期识别系统性淀粉样变性对于最佳患者预后至关重要,刚果红染色应该有一个低门槛。建议使用基于蛋白质组学的淀粉样蛋白分型,因为治疗取决于正确识别淀粉样蛋白类型。
    OBJECTIVE: To determine the prevalence of different amyloid types and frequency of associated systemic amyloidosis in the urinary tract/prostate.
    METHODS: We studied Congo red-positive prostate (n = 150) and urinary tract (n = 767) specimens typed by a proteomics-based method between 2008 and 2020. Clinical follow up was available for a subset (urinary tract, n = 111; prostate, n = 17). Amyloid types were correlated with various clinicopathologic features. For patients with clinical follow up, chart review was performed to establish localized versus systemic disease, frequency of initial diagnosis of amyloidosis on urinary tract/prostate specimens, presence of cardiac disease, and death from disease-related complications.
    RESULTS: The most common amyloid types were AL/AH in urinary tract (479/767, 62 %) and localized ASem1 in prostate (64/150, 43 %). Urinary tract AL/AH amyloid was usually localized, but systemic AL amyloidosis occurred in both sites (urinary tract: 5/71, 7 %; prostate: 2/2, 100 %). ATTR amyloidosis was seen in over a third of cases (urinary tract: 286/767, 37 %; prostate: 55/150, 37 %). Urinary tract/prostate was the site of the initial ATTR amyloidosis diagnosis in 44/48 patients (92 %), and 38/48 (79 %) were subsequently found to have cardiac involvement. Seminal vesicle/ejaculatory duct involvement was pathognomonic for ASem1-type amyloidosis (39/39, 100 %).
    CONCLUSIONS: Over 40 % of patients had systemic amyloidosis, with urinary tract/prostate often the first site in which amyloid was identified. Since early recognition of systemic amyloidosis is critical for optimal patient outcomes, there should be a low threshold to perform Congo red stain. Proteomics-based amyloid typing is recommended since treatment depends on correctly identifying the amyloid type.
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  • 文章类型: Journal Article
    二十二碳六烯酸(DHA;22:6)在视觉中起关键作用,并且是超长链多不饱和脂肪酸(VLC-PUFA)的前体。磷脂酰胆碱(PC)的sn-1和sn-2释放32-和34-碳VLC-PUFA和DHA导致细胞存活介质的合成,elovanoid(ELVs)和神经保护素D1(NPD1),分别。通过基于LC-MS/MS的脂质组学分析和MALDI-分子成像评估年龄相关性黄斑变性(AMD)供体视网膜的黄斑和外周的DHA相关脂质的可用性。我们发现减少的视网膜DHA和VLC-PUFA途径从前体合成omega-3ELV,这可能导致改变的圆盘和光感受器损失。此外,我们比较了omega-3(n-3)脂肪酸与DHA(22:6)和omega-6(n-6)脂肪酸与花生四烯酸(AA;20:4)途径。n-3PC(22:6/22:6,44:12)和n-6PC(20:4/20:4,40:8)显示男性/女性之间的差异,黄斑/周边,和正常/AMD视网膜。AMD男性视网膜边缘增加44:12丰度,而正常女性增加40:8(所有黄斑都有40:8的趋势)。我们还显示,女性AMD从n-3脂肪酸转变为n-6脂肪酸;AMD的大多数变化发生在女性AMD视网膜的外围。从PC释放的DHA和VLC-PUFA导致前存活NPD1和ELV的转化。来自AMD的视网膜周边中ELV的神经保护性前体的损失促进了未补偿的应激和细胞损失。在AMD中,女性视网膜失去外周杆VLC-PUFAs,比男性减少约33%,限制了ELV的形成及其保护性生物活性。
    Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, we compared omega-3 (n-3) fatty acid with DHA (22:6) and omega-6 (n-6) fatty acid with arachidonic acid (AA; 20:4) pathways. n-3 PC(22:6/22:6, 44:12) and n-6 PC(20:4/20:4, 40:8) showed differences among male/female, macula/periphery, and normal/AMD retinas. Periphery of AMD retina males increased 44:12 abundance, while normal females increased 40:8 (all macula had an upward 40:8 tendency). We also showed that female AMD switched from n-3 to n-6 fatty acids; most changes in AMD occurred in the periphery of female AMD retinas. DHA and VLC-PUFA release from PCs leads to conversion in pro-survival NPD1 and ELVs. The loss of the neuroprotective precursors of ELVs in the retina periphery from AMD facilitates uncompensated stress and cell loss. In AMD, the female retina loses peripheral rods VLC-PUFAs to about 33% less than in males limiting ELV formation and its protective bioactivity.
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  • 文章类型: Journal Article
    在这项研究中,通过将发红光的有机荧光染料罗丹明B(RhB)引入金属-有机骨架(Tb-MOFs)中,构建了红绿双发射荧光复合材料(RhB@MOFs)。该样品可用作比率荧光探针,这不仅避免了仪器和环境不稳定引起的误差,而且在检测中具有多种应用。结果表明,RhB@MOF表现出对Fe3的关闭响应和对抗坏血酸(AA)的连续检测的开启响应。该比率荧光探针对Fe3+和AA的连续测定具有较高的灵敏度和良好的选择性。值得一提的是,在紫外灯下肉眼可以清楚地观察到显著的荧光变化,在应用中更方便。此外,详细讨论了Fe3-和AA-诱导的荧光猝灭和恢复的机理。这种比率探针对重金属离子和生物分子表现出突出的识别,为水质监测和生物分子测定提供潜在的应用。
    In this study, a red-green dual-emitting fluorescent composite (RhB@MOFs) was constructed by introducing the red-emitting organic fluorescent dye rhodamine B (RhB) into metal-organic frameworks (Tb-MOFs). The sample can be used as a ratiometric fluorescent probe, which not only avoids errors caused by instrument and environmental instability but also has multiple applications in detection. The results indicated that the RhB@MOFs exhibited a turned-off response toward Fe3+ and a turned-on response for the continuous detection of ascorbic acid (AA). This ratiometric fluorescent probe possessed high sensitivity and excellent selectivity in the continuous determination of Fe3+ and AA. It is worth mentioning that remarkable fluorescence change could be clearly observed by the naked eye under a UV lamp, which is more convenient in applications. In addition, the mechanisms of Fe3+- and AA-induced fluorescence quench and recovery are discussed in detail. This ratiometric probe displayed outstanding recognition of heavy metal ions and biomolecules, providing potential applications for water quality monitoring and biomolecule determination.
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