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关键词： IL-4/13A   Th2 immune response   large yellow croaker (Larimichthys crocea)   mTOR pathway   miR-301a  

摘要： Interleukin-4 (IL-4) and IL-13, predominantly secreted by T helper type 2 (Th2) cells, are pivotal cytokines involved in the Th2 response via the MAPK and mTOR signaling pathways. MicroRNAs (miRNAs) modulate various biological processes by inhibiting mRNA translation or facilitating mRNA degradation. However, research on miRNAs targeting IL-4 and IL-13 and their associated downstream signaling molecules remains limited. In this study, the miR-301a was identified for the first time as a potential regulator of IL-4/13A in Larimichthys crocea ( Lc ) through comprehensive analyses of miRNA-mRNA transcriptomes. The Lc pre-miR-301a comprises 86 nucleotides, including a 21-bp mature miRNA sequence. Secondary structure prediction showed that Lc pre-miR-301a can form a classic hairpin structure. Multiple sequence alignment revealed that the mature Lc miR-301a is highly conserved across fish, mammals, amphibians, and birds. The miR-301a was demonstrated to directly bind to the 3′-UTR of Lc IL-4/13A. Upon induction with phytohemagglutinin (PHA), the expression levels of Lc IL-4/13A were significantly upregulated, leading to the activation of T cell proliferation and differentiation, as well as B cell proliferation in primary head kidney leukocytes (PKLs). Conversely, the overexpression of miR-301a in PKLs significantly inhibited the PHA-induced upregulation of Lc IL-4/13A expression level. Additionally, the stimulatory effects of PHA on T cells and B cells were diminished by the overexpression of Lc miR-301a. Moreover, after transfection with miR-301a mimics and subsequent induction with PHA, the phosphorylation levels of MEK1/2 and 4E-BP1, two critical signaling molecules within the MAPK and mTOR pathways, were significantly reduced in PKLs compared to induction with PHA alone. These findings suggest that miR-301a plays a crucial role in negatively regulating the Th2 immune response by targeting Lc IL-4/13A. This study enhances our understanding of the mechanisms underlying m

关键词： 急性淋巴细胞白血病   儿童   异基因造血干细胞移植   白介素-17   乳酸脱氢酶  

摘要： 目的 探讨外周血白介素-17(IL-17)、乳酸脱氢酶(LDH)与小儿急性淋巴细胞白血病(ALL)异基因造血干细胞移植(allo-HSCT)后复发的关系。方法 采用回顾性研究,选取2019年1月至2023年12月收治的101例ALL患儿,均接受allo-HSCT治疗,收集治疗后24 h外周血IL-17、LDH;以治疗后1年为随访观察时间,统计患儿allo-HSCT后复发情况并分为复发组(n=24)与未复发组(n=77);单因素和多因素Logistic回归分析比较2组一般资料与实验室指标,分析外周血IL-17、LDH与ALL患儿allo-HSCT后复发的关系,评估其预测价值。结果 复发组患儿诱导疗程数>1个占比、未发生慢性移植物抗宿主病(GVHD)占比、IL-17和LDH水平高于未复发组,差异有统计学意义(P<0.05);经多因素Logistic回归分析,结果显示,诱导疗程数>1个、未发生慢性GVHD、IL-17水平高、LDH水平高是ALL患儿allo-HSCT后复发的影响因素(OR>1,P<0.05);绘制ROC曲线,结果显示,外周血IL-17、LDH水平预测ALL患儿allo-HSCT后复发的AUC均>0.7,联合预测的AUC>0.8,联合预测价值更高;绘制决策曲线,结果显示,在阈值范围0.0～0.47、0.5～0.53内,外周血IL-17、LDH水平联合预测ALL患儿allo-HSCT后复发的净收益率明显优于单一指标的净收益率,最大净收益率为0.238;且在高风险阈值0.0～0.55范围内,联合预测的净收益率>0,具有临床意义。结论 外周血IL-17、LDH与ALL患儿allo-HSCT后复发有关,二者水平升高是ALL患儿allo-HSCT后复发的危险因素,且可预测ALL患儿allo-HSCT后复发风险。

关键词： 前列腺癌   前列腺特异性抗原同源异构体2   前列腺健康指数  

摘要： 前列腺癌是男性最常见的恶性肿瘤之一,在世界范围内发病率和病死率呈逐年上升的趋势。前列腺特异性抗原是一种由前列腺腺体分泌的蛋白质,广泛应用于前列腺癌的筛查和监测,在提高早期诊断率的同时,其低特异性的缺点也逐渐暴露。近年来的研究表明,前列腺特异性抗原同源异构体2及其衍生指标性质稳定,特异性更高,极大提高了前列腺癌筛查的准确率,不但避免了一部分非必要前列腺穿刺活检,而且与前列腺癌的病理分级明显相关,在前列腺癌根治术后预后评估等方面展现出了良好的临床价值。

关键词： 癌,肝细胞   γ干扰素   肿瘤坏死因子α   甲胎蛋白异质体   临床病理参数   预后  

摘要： 目的探讨原发性肝细胞癌(HCC)血清中γ干扰素(IFN-γ)、肿瘤坏死因子α(TNF-α)、甲胎蛋白异质体(AFP-L3)的表达与临床病理参数、预后的关系。方法选取2018年2月至2021年2月中国人民解放军北部战区总医院接诊的110例HCC病人作为HCC组,并选取同时期来院体检的90例体检健康者作为对照组,收集两组入院时IFN-γ、TNF-α、AFP-L3,分析IFN-γ、TNF-α、AFP-L3与病理参数之间的关系。共随访36个月,采用Cox回归单因素、多因素模型分析影响HCC病人预后的相关因素。对不同预后病人的IFN-γ、TNF-α、AFP-L3进行Point-biserial相关性分析。结果与对照组比较,HCC组病人的IFN-γ水平[(77.26±16.46)ng/L比(96.85±35.27)ng/L]明显降低,而TNF-α[(258.41±61.28)ng/L比(150.82±114.83)ng/L]和AFP-L3水平[(16.08±2.19)%比(0.28±0.05)%]明显升高。不同病理参数下,与BCLC分期极早期-中期、中高分化、淋巴结未发生转移的病人相比,BCLC分期晚期、低分化、淋巴结发生转移病人的IFN-γ水平明显降低,而TNF-α和AFP-L3水平明显升高。Kaplan-Meier结果显示,BCLC分期、IFN-γ、AFP-L3、TNF-α、分化程度、淋巴结转移均与生存时间有关(P<0.05)。多因素Cox回归模型中,淋巴结发生转移、AFP-L3≥10.26%、TNF-α≥216.27 ng/L、IFN-γ<82.23 ng/L、低分化均是HCC病人预后的独立影响因素。Point-biserial相关性分析发现,TNF-α、AFP-L3与不良预后之间呈现明显正相关性(r=0.47、0.49,P<0.05),IFN-γ与不良预后之间呈现明显负相关性(r=−0.41,P<0.05)。结论IFN-γ在HCC病人中呈低水平表达且TNF-α、AFP-L3呈高表达水平,三者均与HCC病人临床分期、转移、分化有一定的相关性,且是影响HCC病人预后的独立影响因素。

关键词： 鸡传染性法氏囊病病毒(IBDV)   直接免疫荧光法   单克隆抗体   R-藻红蛋白荧光素  

摘要： 【目的】利用R-藻红蛋白荧光素(R-PE)标记鸡传染性法氏囊病病毒(Infectious bursal disease virus, IBDV)单克隆抗体,建立快速检测组织和细胞中IBDV的直接免疫荧光方法。【方法】试验取单克隆抗体细胞4C12复苏后,免疫小鼠制备单克隆抗体腹水,用层析柱进行纯化,通过间接免疫荧光法和ELISA方法对其进行鉴定,并测定抗体效价;通过偶联试剂盒对单克隆抗体进行标记,建立直接免疫荧光法并优化反应条件,检测其特异性、敏感性及稳定性。利用建立的方法对感染IBDV的鸡法氏囊和脾脏进行检测。【结果】纯化的4C12单克隆抗体腹水效价为1∶10^(8);用R-PE标记4C12单克隆抗体,成功建立了直接免疫荧光检测方法,确定最佳反应条件为:IBDV感染DT40细胞48 h、4%多聚甲醛和无水乙醇为固定剂进行双重固定、R-PE-4C12株单克隆抗体工作浓度为24μg/mL、抗体孵育90 min,此条件下荧光效果最佳。建立的直接免疫荧光方法与禽白血病病毒(ALV)、禽网状内皮组织增生症病毒(REV)、禽脑脊髓炎病毒(AEV)和减蛋综合症病毒(EDSV)不发生交叉反应,特异性较好;该方法在病毒含量为10^(3)鸡胚半数感染量(ELD_(50))时仍能检测到阳性信号,灵敏性较好;稳定性试验显示,R-PE-4C12在4℃保存21 d后,仍能产生稳定的荧光信号。建立的直接免疫荧光方法中R-PE-4C12能与感染组织中IBDV结合产生特异性红色荧光;与间接免疫荧光法相比,两者荧光效果没有明显差异。【结论】本研究建立的直接免疫荧光方法具有较好的特异性、敏感性和稳定性,可以用于组织和细胞中IBDV的检测,为实验室IBDV检测提供一种快速有效的检测方案。

关键词： Drug eluting stents   Inflammation   PBMCs   Cytokines   Chemokines   Cell adhesion molecules   Growth factors   ANG   Angiogenin   BMS   Bare metal stents   BP-DES   Biodegradable polymer DES   CCL28   Chemokine (C   C motif) ligand 28   CoCr   Cobalt‑chromium   CoNi   Cobalt‑nickel   CVDs   Cardiovascular diseases   CRP   C-reactive protein   CXCL1   Chemokine (C-X-C motif) ligand 1   D/L   Diameter to length ratio   DES   Drug eluting stent   DET   Drug elution time   DP-DES   Durable polymer drug-eluting stents   EES   Everolimus-eluting stents   ELISA   Enzyme-linked immunosorbent assay   GCP   Good clinical practice   GROα   Growth-regulated protein alpha   h   Hours   H   2   SO   4   Sulphuric acid   ICAM-1   Intercellular adhesion molecule 1   IL   Interleukin   ISR   In-stent restenosis   LST   Late stent thromboses   MCP-1   Monocyte chemoattractant protein 1   MIF   Macrophage migration inhibitory factor   min   Minutes   MMP-9   Matrix metalloproteinase-9   mTOR   Mammalian target of Rapamycin   O.D   Optical density   PBMC   Peripheral blood mononuclear cell   PCI   Percutaneous coronary intervention   PDLLA-PCL   Poly-D, L-lactic acid polycaprolactone   PLGA   Poly-lactic co-glycolic acid   PLLA   Poly-L-lactic acid   PtCr   Platinum‑chromium   Pt-IR   Platinum‑iridium   PVDF-HFP   Co   polymer of vinylidene fluoride and hexafluoropropylene   SD   Standard deviation   SES   Sirolimus-eluting stents   SMC   Smooth muscle cell   ST   Stent thrombose   TGF-β1   Transforming growth factor 1   TNF-α   Tumor necrosis factor alpha   VCAM-1   Vascular adhesion molecule 1   ZES   Zotarolimus-eluting stents  

摘要： Drug eluting stents (DES) are a first-line treatment for ischemic heart diseases. Due to their direct contact with the blood stream, late stent thromboses are a common complication. Thrombosis and inflammation are tightly linked to each other, and are characterized by the activation of inflammatory cells and the secretion of cytokines and chemokines. To date, the influence of DES on the activation of the inflammatory cascade and its corresponding players has not yet been investigated. We performed an in vitro study to observe any potential response of isolated human peripheral blood mononuclear cells (PBMCs) to the structure and drug-coating of different DES. PBMCs from healthy volunteers were incubated with different DES types for 48 h. We measured the secretion of cytokines and chemokines, as well as cell adhesion molecules, and selected growth factors by ELISA. DES were found to significantly increase the cytokine and chemokine secretion of IL-1β, IL-6, IL-8, and ICAM-1, as well as the growth factors ANG and FGF-basic. We further showed that zotarolimus presents with the lowest inflammation-associated protein expression. Our data further revealed that the inflammatory reaction is highly dependent on the DES size, material, and the polymer type of the DES coating. Finally, we tendentially showed that thinner alloys are associated with a lower inflammatory reaction. Our results indicate that DES may potentially lead to an increased inflammatory reaction, considering the different DES designs and properties. This would potentially help to further improve composition and drug selection.

关键词： 间质性肺疾病   支气管肺泡灌洗液   细胞分析  

摘要： 目的探讨间质性肺疾病(Interstitial Lung Disease,ILD)采用支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)细胞分析的诊断价值。方法选取2023年2月-2025年1月我院呼吸科收治的ILD患者60例,设为观察组,另选择同期入院体检的60例健康自然人设为对照组。获取两组受检者支气管肺泡灌洗液后以流式细胞仪进行细胞分析。对比两组受检者以及ILD不同类型患者细胞总数、细胞分类计数以及T淋巴细胞亚群表达水平。结果观察组BALF细胞总数显著高于对照组(P<0.05);观察组巨噬细胞低于对照组,且淋巴细胞、中性粒细胞均高于对照组(P<0.05);观察组CD8+表达高于对照组,且CD4^(+)/CD8^(+)比值低于对照组(P<0.05);不同类型ILD患者中,特发性肺纤维化患者细胞总数明显高于其他类型(P<0.05)。细胞分类中,结节病、隐源性机化性肺炎、特发性肺纤维化患者巨噬细胞表达较高;结节病、过敏性肺炎患者淋巴细胞表达较高;特发性肺纤维化患者中性粒细胞表达最高;嗜酸性粒细胞肺炎患者嗜酸性粒细胞表达最高,T淋巴细胞亚群检测中,结节病患者CD4^(+)/CD8^(+)比值最高,以上统计对比差异均有统计学意义(P<0.05)。结论BALF细胞分析有助于不同类型间质性肺疾病的鉴别,诊断价值显著。

关键词： 肺炎   抗感染治疗   可溶性血管细胞黏附分子-1   内皮素-1   白细胞介素-6  

摘要： 目的:探讨血清可溶性血管细胞黏附分子-1(s VCAM-1)、内皮素-1(ET-1)与白细胞介素-6(IL-6)在老年肺炎患者抗感染治疗中的变化及其对预后的预测价值。方法:选取2021年1月至2024年1月在河南省职工医院接受抗感染治疗的91例老年肺炎患者,在治疗前和治疗10 d时检测血清s VCAM-1、ET-1与IL-6水平,比较患者治疗前后s VCAM-1、ET-1、IL-6水平的差异。在治疗7 d时采用改良临床肺部感染评分系统对患者进行评分,根据评分情况将患者分为预后良好组和预后不良组。其中,预后良好组定义为评分显示完全性改善或病情好转;预后不良组定义为病情恶化或患者死亡。比较两组一般资料和血清s VCAM-1、ET-1与IL-6水平,采用Logistic回归方法分析影响老年肺炎患者预后的独立危险因素。结果:治疗后,老年肺炎患者血清s VCAM-1水平由治疗前的(2402.95±159.73)pg/mL降至(2146.79±64.67)pg/mL(t=14.180,P<0.001);ET-1水平由(2.95±0.52)pg/m L降至(1.14±0.47)pg/m L(t=24.633,P<0.001);IL-6水平由(18.42±9.04)pg/m L降至(8.74±3.21)pg/mL(t=9.625,P<0.001)。与预后不良组比较,预后良好组的年龄、性别、糖尿病史、高血压史等一般资料比较差异无统计学意义(P>0.05),预后良好组的重症患者比例显著低于预后不良组(33.33%比55.00%;χ^(2)=4.297,P=0.038)。与预后不良组比较,预后良好组的s VCAM-1[(2121.41±62.15)pg/m L比(2179.12±66.36)pg/m L;t=4.267,P<0.001]、ET-1[(1.16±0.69)pg/m L比(2.24±0.81)pg/mL;t=6.864,P<0.001]及IL-6[(7.73±3.34)pg/mL比(10.02±3.51)pg/mL;t=3.174,P<0.001]均显著降低。Logistic回归分析结果显示,重症肺炎(OR=5.786,95%CI 1.049-31.919,P=0.044)、s VCAM-1升高(OR=4.869,95%CI 1.608-14.737,P<0.001)、ET-1升高(OR=5.333,95%CI 1.610-17.664,P<0.001)及IL-6升高(OR=5.053,95%CI 1.571-16.251,P<0.001)是影响老年肺炎患者预后的独立危险因素,该预测模型的受试者工作特征曲线下面积为0.890,敏感度、特异度分别为92.98%、89.18%。结论:在老年肺炎抗感染治疗中,s VCAM-1、ET-1与IL-6之间存在复杂的联系,其血清水平升高提示预后不良。

关键词： Time-restricted eating   Dietary intervention   Blood glucose   Body weight   Type 2 diabetes   ALT   alanine aminotransferase   AST   aspartate aminotransferase   BMI   body mass index   CGM   continuous glucose monitor   HbA1c   glycated hemoglobin   HDL-C   high-density lipoprotein cholesterol   HOMA   homeostasis model assessment   HOMA2-β   HOMA2 of β-cell function   HOMA2-IR   HOMA2 of insulin resistance   IFN   interferon   IL   interleukin   LDL-C   low-density lipoprotein cholesterol   MASLD   metabolic dysfunction-associated steatotic liver disease   PHQ-9   patient health questionnaire-9   SDSCA   summary of diabetes self-care activities   TNF-α   tumor necrosis factor-α   TRE   time-restricted eating   WHO-5   World Health Organization five-item well-being index  

摘要： Background & aims Time-restricted eating (TRE) is a newly emerging dietary strategy that reduces body weight and improves glucose tolerance in individuals with overweight or obesity. However, whether TRE is effective in improving glycemic control in individuals with diabetes remains unexplored. Herein, we aimed to investigate the effects of TRE intervention on glycemic control in patients with type 2 diabetes. Methods In this single-center, open-label, self-controlled trial, 18 overweight or obese adults with type 2 diabetes inadequately controlled on lifestyle modification alone or in combination with metformin and/or α-glycosidase inhibitors were enrolled to receive a 10-h TRE for 12 weeks. The effects of TRE on glucose metabolism, body weight, body composition and other metabolic parameters were evaluated in these participants following the intervention. Results The 12-week TRE intervention not only significantly reduced body weight (−1.72 ± 1.83 kg, P < 0.001), but also remarkably improved glycemic control, with reduced glycated hemoglobin (HbA1c; −0.69 % ± 0.48 %, P < 0.001) and fasting blood glucose (−0.90 ± 1.27 mmol/L, P = 0.008) levels. In addition, TRE also significantly reduced triglyceride level (−0.26 mmol/L [−0.52 to −0.04 mmol/L], P = 0.004) and fatty liver index (−8.64 [−15.4 to −2.87], P = 0.003) after 12 weeks of intervention. Notably, the benefits for HbA1c reduction lasted for up to 1 year. Conclusions TRE can improve glycemic control up to 1 year in individuals with type 2 diabetes. Our findings indicate that TRE may represent a novel diet management option for patients with type 2 diabetes.

关键词： Breast Cancer   IBD   Incident Cancer   Biologics   CD   Crohn’s disease   CI   confidence interval   IBD   inflammatory bowel diseases   IQR   interquartile range   TNF   tumor necrosis factor  

摘要： Background & Aims Breast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD). The aim of our study was to evaluate incident cancer rate (recurrence or new-onset cancer) in a cohort of patients with IBD with a history of breast cancer according to the subsequent IBD treatment provided. Methods A multicenter retrospective study included consecutive patients with IBD with prior breast cancer. The inclusion date corresponded to the diagnosis of index malignancy. Follow-up lasted from cancer diagnosis until the occurrence of incident cancer. Results Among 207 patients included (median disease duration, 13 years [interquartile range, 6–21]), first-line treatment (median interval of 28 months [interquartile range, 7–64]) was a conventional immunosuppressant in 19.3% of patients, anti–tumor necrosis factor in 19.8%, vedolizumab in 7.2%, and ustekinumab in 1.9%. After a median follow-up of 71 months (interquartile range, 34–148), 42 (20%) incident cancers were observed (34 breast cancer recurrences). Adjusted incidence rates per 1000 person-years were 10.2 (95% confidence interval, 6.0–16.4) for the untreated arm and 28.9 (95% confidence interval, 11.6–59.6) for exposed patients ( P = .0519). There was no significant difference between treated patients and control subjects regarding incident cancer-free survival rates ( P = .4796). In multivariable analysis, factors associated with incident cancer were stage T4d ( P = .036), triple negative tumor ( P = .016), and follow-up of less than 71 months ( P = .005). Conclusions We did not find a statistically significant increase in incident breast cancer related to IBD treatment beyond the already known poor prognostic factors of breast cancer.