Absent in melanoma 2 attenuates proliferation and migration and promotes apoptosis of human colorectal cancer cells by activating P38MAPK signaling pathway

Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.

Drosophila Eyes Absent Homologue 2 is up-regulated in lung adenocarcinoma

Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to identify the expression of Drosophila Eyes Absent Hemologue 2 （EYA2） in non-small cell lung cancer （NSCLC） and to investigate their correlation with clinical parameters. Methods： Fresh, paired lung samples （n = 59） of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People＇s Liberation Army General Hospital. Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue. Clinical data, pathologic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed. Results： EYA2 expression was found located in cytoplasm and nucleus, but mostly in cytoplasm. The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry, which was correlated with histology type, but not correlated with gender, age, pTNM stage, histological differentiation and lymph node metastasis. Compared with normal lung tissue, the expression of EYA2 significantly was up-regulated in lung adenocarcinoma, while no significant difference in lung squamous cell carcinoma. Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC. Conclusion： Expression of EYA2 was augmented in lung adenocarcinoma. EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.

Expression and localization of absent in melanoma 2 in the injured spinal cord

In traumatic brain injury, absent in melanoma 2(AIM2) has been demonstrated to be involved in pyroptotic neuronal cell death. Although the pathophysiological mechanism of spinal cord injury is similar to that of brain injury, the expression and cellular localization of AIM2 after spinal cord injury is still not very clear. In the present study, we used a rat model of T9 spinal cord contusive injury, produced using the weight drop method. The rats were randomly divided into 1-hour, 6-hour, 1-day, 3-day and 6-day(post-injury time points) groups. Sham-operated rats only received laminectomy at T9 without contusive injury. Western blot assay revealed that the expression levels of AIM2 were not significantly different among the 1-hour, 6-hour and 1-day groups. The expression levels of AIM2 were markedly higher in the 1-hour, 6-hour and 1-day groups compared with the sham, 3-day and 7-day groups. Double immunofluorescence staining demonstrated that AIM2 was expressed by NeuN+(neurons), GFAP+(astrocytes), CNPase+(oligodendrocytes) and CD11 b+(microglia) cells in the sham-operated spinal cord. In rats with spinal cord injury, AIM2 was also found in CD45+(leukocytes) and CD68+(activated microglia/macrophages) cells in the spinal cord at all time points. These findings indicate that AIM2 is mainly expressed in neurons, astrocytes, microglia and oligodendrocytes in the normal spinal cord, and that after spinal cord injury, its expression increases because of the infiltration of leukocytes and the activation of astrocytes and microglia/macrophages.

Surgical treatment for severe cubital tunnel syndrome with absent sensory nerve conduction

For severe cubital tunnel syndrome, patients with absent sensory nerve action potential tend to have more severe nerve damage than those without. Thus, it is speculated that such patients generally have a poor prognosis. How absent sensory nerve action potential affects surgical outcomes remains uncertain owing to a scarcity of reports and conflicting results. This retrospective study recruited one hundred and fourteen cases(88 patients with absent sensory nerve action potential and 26 patients with present sensory nerve action potential) undergoing either subcutaneous transposition or in situ decompression. The minimum follow-up was set at 2 years. Primary outcome measures of overall hand function included their McGowan grade, modified Bishop score, and Disabilities of the Arm, Shoulder, and Hand Questionnaire(DASH) score. For patients with absent sensory nerve action potential, 71 cases(80.7%) achieved at least one McGowan grade improvement, 76 hands(86.4%) got good or excellent results according to the Bishop score, and the average DASH score improved 49.5 points preoperatively to 13.1 points postoperatively. When compared with the present sensory nerve action potential group, they showed higher postoperative McGowan grades and DASH scores, but there was no statistical difference between the modified Bishop scores of the two groups. Following in situ decompression or subcutaneous transposition, great improvement in hand function was achieved for severe cubital tunnel syndrome patients with absent sensory nerve action potential. The functional outcomes after surgery for severe cubital tunnel syndrome are worse in patients with absent sensory nerve action potential than those without. This study was approved by the Ethical Committee of Huashan Hospital, Fudan University, China(approval No. 2017142).

Absent-minded Mark Twain

The famous American writer MarkTwain was well—known for his absent-mind-edness.One day,when he was riding in a train,the conductor asked him for his ticket.MarkTwain looked for the ticket in all his pockets.but 11e didn’t find it.At last,the

教育元宇宙背景下线上教学的虚实互促研究

元宇宙描绘未来的虚实共生、虚实链接。该文给出元宇宙背景下线上教学场景,针对线上教学中的学生“虚位”与作业“虚化”两个问题,分析线上教学的虚拟数字对象与物理实体对象的特点,提出采用多模态感知学生状态、推演式知识运用、区块链数字作业价值信任和教师数字成果价值流动等虚实互促着力点,为提升线上教学质量提供支撑。

论虚构叙事中的不在场叙述者、零叙述者与无叙述者

在叙事理论研究中,虚构叙事中的叙述者是一个极为重要的概念。在探讨叙事文本的讲述及其内在交流中,它都起着核心作用。伴随叙述者这一中心概念,产生了一系列与之相关的附属概念。本文集中探讨不在场叙述者、零叙述者与无叙述者三个相互关联的概念。厘清这三个概念的确切含义,指出其功用,说明其存在的某些含混与矛盾之处,有助于理解叙事文本的构成及叙事的内在机制。不在场叙述者、零叙述者和无叙述者所表现的叙述情境,呈现的或者是一种局部的、部分的叙述者暂时隐蔽的状态;或者其概念本身便具有矛盾性,难于成立;或者是以一种叙述声音代替另一种叙述声音。从整体上说,叙述者作为叙述主体,是叙事文本中不可或缺的要素,叙述者、叙述、文本之间的关系缺一不可。

Unroofed coronary sinus,left-sided superior vena cava and mitral insufficiency:A case report and review of the literature

BACKGROUND Unroofed coronary sinus(UCS)is a rare subtype of atrial septal defect.It is frequently associated with a persistent left superior vena cava and is often part of a more intricate cardiac malformation.CASE SUMMARY This report describes a rare case of an adolescent patient with UCS featuring atrial situs solitus,absence of the right superior vena cava and a persistent left superior vena cava draining into the left atrium consistent with total unroofing of the coronary sinus.This was associated with concurrent severe mitral insufficiency secondary to redundant and prolapsing leaflets,and a substantial left-to-right shunt across the coronary sinus orifice.A comprehensive examination of the existing literature is included,shedding light on the diagnostic challenges of UCS and describing the available surgical options within the context of mitral valve surgery.CONCLUSION UCS is a complex condition requiring careful consideration of associated anomalies and a tailored surgical approach.

艾叶/茶叶水提物促进皮肤感染模型大鼠创面愈合的协同作用及机制研究

目的探讨艾叶水提物和茶叶水提物对皮肤感染模型大鼠的协同治疗作用及其机制。方法实验分两个部分进行:第一部分将皮肤感染模型大鼠随机分为模型组、西药组、艾叶水提物组、茶叶水提物组、2∶1组(艾叶水提物与茶叶水提物质量比为2∶1)、1∶1组(艾叶水提物与茶叶水提物质量比为1∶1)和1∶2组(艾叶水提物与茶叶水提物质量比为1∶2),每组7只。比较治疗前后各组大鼠创面面积;ELISA法检测各组大鼠血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-1β、IL-18水平。第二部分随机选取7只大鼠为正常组,将皮肤感染模型大鼠随机分为模型组、2∶1组(艾叶水提物与茶叶水提物质量比为2∶1),每组7只。Western blot法检测各组大鼠皮肤组织黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、含有CARD的凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing CARD,ASC)和Caspase-1蛋白表达水平;ELISA法检测各组大鼠血清AIM2、ASC、Caspase-1及IL-1β、IL-18水平。结果第一部分,与模型组比较,西药组、艾叶水提物组、茶叶水提物组和3个不同比例组感染创口收缩明显,创面面积明显减小,且促炎因子TNF-α、IL-1β、IL-18的表达水平均显著降低(P<0.05)。其中西药组、2∶1组效果更明显,两组促炎因子TNF-α、IL-1β水平比较,差异无统计学意义(P>0.05)。第二部分,与正常组比较,模型组感染创面组织中AIM2、ASC、Caspase-1蛋白表达水平和血清IL-1、IL-18水平均显著升高(P<0.05)。与模型组比较,2∶1组感染创面组织中AIM2、ASC、Caspase-1蛋白表达水平和血清IL-1、IL-18水平均显著降低(P<0.05)。结论艾叶水提物和茶叶水提物对治疗皮肤感染模型大鼠存在协同作用,艾叶水提物与茶叶水提物质量比为2∶1是最优比例。其协同机制可能与AIM2炎症小体活化和细胞焦亡通路有关。

黑色素瘤缺乏因子2与银屑病关系的最新研究进展

银屑病是一种由环境诱因刺激、多基因遗传控制和免疫因素调节等多因素共同作用导致的慢性、炎症性、复发性、系统性疾病,炎症因素在该疾病的发生和发展中具有重要作用。全外显子组测序(whole-exome sequencing,WES)鉴定出黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)基因为银屑病的易感基因。AIM2基因编码的AIM2蛋白可识别双链DNA,诱导凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)的胱天蛋白酶募集结构域(caspase activation and recruitment domain,CARD)招募半胱氨酸天冬氨酸蛋白水解酶-1(cysteine-requiring aspartate protease-1,caspase-1),组成高分子量蛋白复合体——AIM2炎症小体。国内外研究者聚焦于AIM2基因及AIM2炎症小体在银屑病中的作用开展了大量研究,并取得一定的研究进展。本文对近五年来有关AIM2基因及AIM2炎症小体在银屑病中的研究进展进行一综述。

Epigenetic Silencing of Eyes Absent 4 Gene by Acute Myeloid Leukemia 1-Eight-twenty-one Oncoprotein Contributes to Leukemogenesis in t（8;21） Acute Myeloid Leukemia

Background： The acute myeloid leukemia 1 （AML1）-eight-twenty-one （ETO） fusion protein generated by the t（8;2 1）（q22;q22） translocation is considered to display a crucial role in leukemogenesis in AML. By focusing on the anti-leukemia effects of eyes absent 4 （EYA4） gene on AML cells, we investigated the biologic and molecular mechanism associated with AML 1 -ETO expressed in t（8;21） AML. Methods： Qualitative polymerase chain reaction （PCR）, quantitative reverse transcription PCR （RT-PCR）, and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines. Different plasmids （including mutant plasmids） of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4. Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4. Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region. The influence ofEYA4 gene in the cell proliferation, apoptosis, and cell clone-forming ability was detected by the technique of Cell Counting Kit-8, flow cytometry, and clonogenic assay. Results： EYA4 gene was hyperrnethylated in AMLI-ETO＋ patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells, compared to HL-60 and SKNO-1-siA/E cells, respectively. We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA 4 gene by binding at AML 1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases. Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AMLI-ETO cell lines. We also found EYA4 transfection increased apoptosis of Kasumi- 1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control, respectively. Conclusions： Our study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene. In addition, we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML 1-ETO＋ t （8;21 ） AML.

FEES联合DSS对卒中后咽反射消失吞咽障碍的诊断价值

目的评估纤维鼻咽喉镜吞咽功能检查(FEES)联合视频透视吞咽造影(DSS)在卒中后咽反射消失患者中的应用价值。方法选取徐州市中心医院卒中后咽反射消失的住院患者90例,均进行FEES及DSS检查。结果(1)FEES与DSS对不同稠度食物误吸检出率的差异均无统计学意义(P>0.05)。(2)咽期FEES检查结果:咽期吞咽障碍40例,其中渗漏34例,误吸29例,梨状窝残留35例,会厌谷残留38例。咽期DSS检查结果:咽期吞咽障碍38例,其中渗漏34例,误吸27例,梨状窝残留31例,会厌谷残留35例。以FEES检查为金标准,DSS检查在渗漏、误吸、梨状隐窝残留及会厌谷残留方面的灵敏度分别为100.00%、93.10%、88.57%、92.11%,特异度高达100.00%。两种检查方法在评估咽期吞咽障碍上一致性较强,Kappa值为0.85。(3)FEES检查结果:咽部感觉障碍25例,咽肌收缩无力21例,Yale分级法3级及以上43例,咽部异常分泌10例。DSS检查结果:唇闭合障碍7例,咀嚼失用3例,口腔残留15例,舌骨上抬障碍15例,环咽肌开放障碍13例,食管蠕动异常2例。结论FEES与DSS对误吸检出率基本一致、咽期吞咽障碍检出一致性较强,DSS评估包括从口腔期到咽期到食道期,而FEES能直接观察咽期、咽部感觉及咽肌收缩,在卒中后咽反射消失病变中有不可替代的价值。两种检查方法联用既能相互佐证,又能相互补充。

炎症小体在缺血性脑卒中中的激活和作用机制的研究进展

缺血性脑卒中是临床常见的心血管疾病之一,致死率及致残率均较高。核苷酸结合寡聚化结构域样受体蛋白(NLRP)1、NLRP3、黑色素瘤缺乏因子2等炎症小体是缺血性脑卒中炎症反应的重要机制。而钾离子外流、活性氧过量产生以及缺氧诱导因子-1α信号通路和胱天蛋白酶1信号通路激活等是炎症小体激活的主要机制,并在缺血性脑卒中中通过炎症和(或)凋亡过程引发细胞死亡,发挥神经保护作用。因此,深入研究NLRP3等炎症小体引发缺血性脑卒中及炎症反应的相关机制,可以为疾病的抗炎治疗提供可靠依据。

Surgical outcome after complete repair of tetralogy of Fallot with absent pulmonary valve: comparison between bovine jugular vein-valved conduit and monocusp-valve patch

Background The prognosis of tetralogy of Fallot with absent pulmonary valve (TOF/APV) without operation is poor. We evaluated the surgical outcome of TOF/APV in a single center. Methods Twenty-two TOF/APV patients underwent complete surgical correction in our hospital. Right ventricular outflow tract reconstruction was performed using bovine jugular vein (BJV)-valved conduit implantation (n=10), homograft-valved conduit implantation (n=2), or monocusp-valve patch (n=10). Health-related quality of life (QOL) was evaluated during follow-up. Results The overall survival at 5 and 10 years was 86.4±7.3% (confidence interval 69.4–97.2%). The survival rates were significantly different between patients with and without bronchial stenosis (40 and 100%, P=0.0003, log-rank test). The survival of patients aged>6 months was higher than those≤6 months (100 vs. 40%, P=0.0003, log-rank test). Patients with BJV-valved conduits had higher systolic gradients from the right ventricle to the pulmonary artery (RV–PA) compared to those with monocusp-valve patches. BJV-valved conduit implantation was a risk factor for post-operative pulmonary-valve stenosis. The QOL score for patients with BJV-valved conduits was lower than those with monocusp-valve patches (P<0.05). No reoperation was performed during follow-up. Conclusions Bronchial stenosis and lower age (≤6 months) were the main factors influencing post-operative survival. The use of a BJV-valved conduit was a main reason for RV–PA restenosis;thus, the use of a BJV-valved conduit may increase the need for repeat intervention and decrease the post-operative quality of life.

Two naturally derived small molecules disrupt the sineoculis homeobox homolog 1–eyes absent homolog 1 (SIX1–EYA1) interaction to inhibit colorectal cancer cell growth

Background:Emerging evidence indicates that the sineoculis homeobox homolog 1−eyes absent homolog 1(SIX1–EYA1)transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes,such as cell-cycle progression and metastasis.However,the roles of the SIX1–EYA1 transcriptional complex and its targets in colorectal cancer(CRC)are still being investigated.This study aimed to investigate the roles of SIX1–EYA1 in the pathogenesis of CRC,to screen inhibitors disrupting the SIX1–EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.Methods:Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues(collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine,West China Hospital of Sichuan University,between 2016 and 2018,n=24).In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1–EYA1 interaction.Cell proliferation,cell survival,and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay,clonogenic assay,and Boyden chamber assay,respectively.The Amplified Luminescent Proximity Homogeneous Assay Screen(AlphaScreen)method was used to obtain small molecules that specifically disrupted SIX1–EYA1 interaction.CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts,and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.Results:Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues(for SIX1,7.47±3.54 vs.1.88±0.35,t=4.92,P=0.008;for EYA1,7.61±2.03 vs.2.22±0.45,t=6.73,P=0.005).The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1(CCNA1)and transforming growth factor beta 1(TGFB1)by binding to the myocyte enhancer factor 3 consensus.Knockdown of both SIX1 and EYA1 could decrease cell proliferation,cell invasion,tumor growth,and in vivo tumor growth(all P<0.01).Two small molecules,NSC0191 and NSC0933,were obtained using AlphaScreen and they could significantly inhibit the SIX1–EYA1 interaction with a half-maximal inhibitory concentration(IC50)of 12.60±1.15μmol/L and 83.43±7.24μmol/L,respectively.Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.Conclusions:Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1,causing the pathogenesis of CRC.Pharmacological inhibition of the SIX1–EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.

基于Notch信号通路探讨芪蛭皱肺颗粒对慢性阻塞性肺疾病大鼠Th1/Th2免疫平衡的调节机制

目的探讨果蝇双翅边缘缺刻同源基因(Notch)信号通路在慢性阻塞性肺疾病(COPD)辅助性T细胞1(Helper T cells 1,Th1)和辅助性T细胞2(Helper T cells 2,Th2)失衡中的作用及芪蛭皱肺颗粒的干预机制。方法70只Wistar大鼠随机挑选10只作为空白对照组,其余大鼠均采用香烟烟雾(CS)联合气管滴注脂多糖(Lipopolysaccharide,LPS)法建立COPD模型,空白对照组及造模组各随机挑选3只大鼠验证造模是否成功。造模结束进行灌胃给药干预,造模组大鼠随机分为模型对照组、阳性对照组(67.5μg·kg^(-1))及芪蛭皱肺颗粒高中低剂量组(3.24、1.62、0.81 g·kg^(-1)),分别给予生理盐水、醋酸地塞米松混悬液、芪蛭皱肺高、中、低剂量混悬液进行灌胃干预,空白对照组同模型对照组,灌胃等体积生理盐水。经28天造模及28天治疗后,采用动物肺功能测试系统检测吸气峰流速(Peak Inspiratory Flow,PIF)和呼气峰流速(Peak Expiratory Flow,PEF),处死大鼠提取肺脏、脾脏、血清及支气管肺泡灌洗液(BALF),苏木素-伊红(HE)染色评价肺组织病理变化,酶联免疫吸附实验法(ELISA)测定血清及BALF中肿瘤坏死因子-α(TNF-α)含量,流式细胞仪检测脾脏Th1/Th2细胞水平,免疫组织化学法(Immunohistochemistry,IHC)及蛋白免疫印迹法(Western blot)检测肺组织Notch1、Hes家族发状分裂相关增强子1(Hes1)、Hey家族发状分裂相关增强子1(Hey1)蛋白水平,实时荧光定量聚合酶链式反应(Real-time PCR,RT-PCR)检测肺组织Notch1、Hes1、Hey1基因表达水平。结果与空白对照组比较,模型对照组大鼠肺功能显著降低(P<0.05),肺组织出现炎性细胞浸润、支气管结构破坏等病变,血清及BALF中TNF-α含量显著升高(P<0.05),脾Th1细胞百分比显著降低(P<0.05),Th2细胞百分比显著升高(P<0.05),肺组织Notch1、Hes1、Hey1蛋白及mRNA表达显著升高(P<0.05),差异均具有统计学意义;与模型对照组比较,各给药组大鼠肺功能显著升高(P<0.05),肺组织病理损伤均有所减轻,血清及BALF中TNF-α含量显著降低(P<0.05),脾Th1细胞百分比显著升高(P<0.05),Th2细胞百分比显著降低(P<0.05),肺组织Notch1、Hes1、Hey1蛋白及mRNA表达显著降低(P<0.05),差异均具有统计学意义。结论芪蛭皱肺颗粒通过抑制Notch信号通路调节Th1/Th2平衡,从而改善COPD大鼠肺功能及病理损伤,影响其免疫功能。

黑色素瘤缺乏因子2炎症小体在牙周炎及糖尿病中的研究进展

黑色素瘤缺乏因子2(AIM2)炎症小体是由AIM2、凋亡相关斑点样蛋白及半胱天冬氨酸特异性蛋白酶1组成的大分子蛋白质复合物,活化后可释放白细胞介素-1β、白细胞介素-18等促炎细胞因子并诱导焦亡,在炎症性疾病的发生发展过程中有重要作用。目前的研究表明AIM2炎症小体的激活参与了牙周炎的发展,还可以直接或间接影响胰岛素信号通路的传导,从而参与糖尿病的发生发展。牙周炎与糖尿病互为双向关系,AIM2作为DNA传感器在牙周炎和糖尿病发生发展中所扮演的角色已经引起广泛关注。本文重点综述了AIM2炎症小体在两种疾病中的相关研究,并对AIM2炎症小体在两种疾病双向关系中的潜在机制进行探讨,为后续牙周炎和糖尿病的发病机制研究提供基础。

3~6岁儿童乳前牙发育异常的研究

目的:探讨3~6岁儿童乳前牙发育异常的发生情况。方法:选择2023年1~12月来我院就诊的3~6岁儿童,最终纳入9432张曲面断层片,记录乳前牙和继承恒牙发育异常的情况,应用SPSS 24.0统计软件分析所得的数据。结果:乳前牙发育异常的总发生率为3.90%,性别间差异无统计学意义(P=0.483)。乳前牙先天缺失最常见,发生率为2.15%,性别间差异无统计学意义(P=0.887),单侧缺失多于双侧(P=0.000),下颌缺失多于上颌(P=0.000),右侧缺失多于左侧(P=0.000),乳前牙先天缺失其继承恒牙有4种情况(缺失70.85%,正常25.83%,融合牙1.85%和额外牙1.48%)。乳前牙融合牙的发生率为1.84%,性别间差异无统计学意义(P=0.110),单侧融合多于双侧(P=0.000),下颌融合多于上颌(P=0.000),右侧融合多于左侧(P=0.012),乳前牙融合牙其继承恒牙有3种情况(缺失52.33%,正常43.52%和融合牙4.15%)。乳前牙额外牙的发生率为0.13%,其继承恒牙有2种情况(额外牙33.33%,无额外牙66.67%)。乳前牙畸形舌尖的发生率为0.42‰,乳前牙双根的发生率为0.21‰,乳前牙阻生牙的发生率为0.11‰。结论:乳前牙发育异常发生率3.90%,乳前牙发育异常在一定程度上影响乳牙和乳牙列,甚至可能并发恒牙和恒牙列异常。对乳前牙发育异常的患儿,可通过影像学检查了解继承恒牙的情况,早期发现和诊断恒牙异常,以便采取合理的治疗方案。

急性痛风性关节炎患者外周血黑色素瘤缺乏因子2信号通路相关细胞因子及焦孔素D表达变化观察

目的观察急性痛风性关节炎患者外周血黑色素瘤缺乏因子2(AIM2)炎症小体信号通路相关细胞因子[AIM2、双链DNA(dsDNA)、IL-1β、IL-18]及焦孔素D表达变化,并分析单个核细胞中AIM2、焦孔素D与急性痛风性关节炎患者病情[WBC、PLT、ESR、CRP、IL-1β、IL-18、BMI、UA、BUN、肌酐(SCr)、肌酐清除率(CCr)、TG、TC]的关系,以探讨AIM2炎症小体信号通路介导的细胞焦亡在急性痛风性关节炎发生、发展中的作用。方法纳入30例急性痛风性关节炎患者(观察组)和30例健康对照者(对照组),比较两组外周血单个核细胞(PBMCs)中AIM2、焦孔素D及血清中IL-1β、IL-18、双链DNA(dsDNA)水平。采用Spearman相关分析AIM2 mRNA和焦孔素D mRNA与急性痛风性关节炎患者病情相关指标(IL-1β、IL-18、WBC、PLT、ESR、CRP、BMI、UA、BUN、SCr、CCr、TG、TC)的关系。结果与对照组比较,观察组PBMCs中AIM2和焦孔素D mRNA的表达水平高(P均<0.05),血清dsDNA、IL-1β、IL-18水平高(P均<0.01)。PBMCs中AIM2 mRNA与WBC、ESR、CRP、BMI、TC、TG、sCr正相关(P均<0.05),焦孔素D mRNA与ESR、IL-1β、sCr正相关(P均<0.05)。结论急性痛风性关节炎患者外周血PBMCs中AIM2、焦孔素D及血清中dsDNA、IL-1β、IL-18水平均升高,AIM2炎症小体介导的细胞焦亡可能参与了急性痛风性关节炎的发生、发展。

血管性痴呆患者血清AIM2和载脂蛋白J水平表达与临床病情程度评估及预后的关系研究

目的探究血管性痴呆(vascular dementia,VD)患者血清黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、载脂蛋白J(apolipoprotein J,Apo J)水平与病情程度及预后的关系。方法选取滨州市第二人民医院2020年10月~2022年9月接诊的血管性痴呆患者128例作为研究组,依据简易精神状态检查表(mini-mental stateexamination,MMSE)评分评估病情严重程度,将研究组分为轻度组(n=43)、中度组(n=54)和重度组(n=31);治疗90天后根据日常生活能力(activities of daily living,ADL)量表评分评估患者预后,分为Ⅰ级组(n=66)、Ⅱ级组(n=40)和Ⅲ级组(n=22);另选取同期正常健康体检者96例作为对照组。应用实时荧光定量PCR(qRT-PCR)、酶联免疫吸附测定(ELISA)法检测血清AIM2和Apo J表达水平,并进行各组间比较;采用Spearman法分析血清AIM2,Apo J表达水平与MMSE评分的相关性以及与预后的关系;采用Logistic回归分析血管性痴呆患者预后影响因素。结果与对照组比较,研究组血清AIM2 mRNA(3.11±0.57 vs 1.06±0.23)表达水平显著升高,血清Apo J表达水平显著降低(68.83±12.24 ng/L vs 81.07±13.15 ng/L),差异具有统计学意义(t=32.054,7.174,均P<0.001);重度组血清AIM2 mRNA表达水平显著高于轻度组和中度组(q=12.807,15.780),血清Apo J表达水平、MMSE评分均明显低于轻度组和中度组(q=26.021,4.301;12.191,20.802),且中度组血清AIM2 mRNA表达水平显著高于轻度组(q=14.688),血清ApoJ表达水平、MMSE评分均低于轻度组(q=20.338,37.537),差异具有统计学意义(均P<0.001);血管性痴呆患者Ⅲ级组血清AIM2 mRNA(5.27±0.60)表达水平显著高于Ⅱ级组(3.36±0.58)、Ⅰ级组(2.23±0.55),而血清ApoJ(51.22±12.21 ng/L)表达水平显著低于Ⅱ级组(64.15±12.23 ng/L)、Ⅰ级组(77.53±12.25ng/L);Ⅱ级组血清AIM2 mRNA表达水平显著高于Ⅰ级组,而血清ApoJ表达水平显著低于Ⅰ级组,差异具有统计学意义(q=5.630~30.740,均P<0.001);血管性痴呆患者血清AIM2水平与MMSE评分呈负相关性,与预后(ADL分级)呈正相关性(r=-0.535,0.432,均P<0.001);血管性痴呆患者血清ApoJ水平与MMSE评分呈正相关性,与预后(ADL分级)呈负相关性(r=0.467,-0.496,均P<0.001);血清AIM2 mRNA[OR(95%CI):2.746(1.481~5.091),Apo J[OR(95%CI):0.496(0.311~0.791),MMSE评分[OR(95%CI):0.568(0.347~0.931)为血管性痴呆患者预后的影响因素(均P<0.05)。结论血管性痴呆患者血清AIM2 mRNA表达水平升高,血清Apo J表达水平降低,与患者病情程度及预后密切相关,可有效评估患者预后。