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关键词： Italian simmental   SCS genomic values   functional haplotypes   immune genes  

摘要： This study aimed to investigate the potential association between the breeding values for somatic cell scores in milk (SCS) and polymorphisms in genes that encode for cytokines ( and ) and . These genes were selected because of their critical roles in immune regulation and their known involvement in mastitis-related inflammatory processes. To gain a comprehensive breeding perspective, the association study was conducted simultaneously with breeding values for productive traits in 558 Italian Simmental cows, a widespread dual-purpose dairy and beef bovine breed that is adaptable to harsh farming and breeding *** association analysis showed that only three of the nine chosen markers, one in and two in , significantly associated with somatic cell breeding values, without effects on the other dairy traits. Only one of the two SNPs has been considered, being in linkage disequilibrium. The two remaining SNPs were grouped into three haplotypes (A-G, 88%; A-A, 5%; and T-G, 7%, respectively), and Haplotype-3 significantly affected the breeding values for SCS. The combination of Haplotype-1 with Haplotype-2 resulted in a significant decrease, while with Haplotype-3 led to a considerable improvement in SCS breeding values. It was noted that the functional haplotypic combinations examined did not significantly affect the production breeding values. This research could provide interesting polymorphisms for genomic evaluation of Italian Simmental dairy cows, increasing the accuracy of breeding values, assisting breeders in selecting animals with enhanced immune responses, minimising the economic impact of mastitis, and improving overall herd health and productivity.

关键词： immunodermatology   inflammation/inflammatory   lasers   pyoderma gangrenosum   scars   wounds and wound healing   IBD   inflammatory bowel disease   IL   interleukin   PG   Pyoderma gangrenosum  

摘要： Introduction Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that manifests as painful, nonhealing ulcers. The rarity of PG, combined with its variable clinical presentation, makes timely diagnosis challenging, and the lack of Food and...

关键词： 冠心病   壳多糖酶3样蛋白1   白细胞介素-6   脂蛋白相关磷脂酶A 2   疾病严重程度   诊断价值  

摘要： 目的:探讨血清壳多糖酶3样蛋白1(CHI3L1)、白细胞介素-6(IL-6)、脂蛋白相关磷脂酶A 2(Lp-PLA 2)联合检测对冠心病(CHD)的诊断价值及与疾病严重程度的相关性。方法:选取2024年1月-12月咸宁市中心医院心血管内科住院治疗的138例冠心病患者作为实验组,另选取同期因胸痛入院且经冠脉造影排除冠心病的138例患者作为对照组。采用全球急性冠状动脉事件注册(GRACE)评分将实验组分为轻度组(≤108分,n=45)、中度组(109-140分,n=55)、重度组(≥140分,n=38)。检测两组血清CHI3L1、IL-6、Lp-PLA2水平,比较组间差异;采用Spearman秩相关分析三者与疾病严重程度的相关性;通过多因素Logistic回归分析冠心病发生的危险因素;利用受试者工作特征(ROC)曲线评估三者单独及联合检测对冠心病的诊断价值。结果:实验组合并高血压、糖尿病、高血脂及吸烟史的比例均高于对照组(P<0.01);实验组血清CHI3L1、IL-6、Lp-PLA 2水平均显著高于对照组(P<0.01)。血清CHI3L1、IL-6、Lp-PLA 2水平在重度组>中度组>轻度组(P<0.05)。Spearman秩相关分析显示,三者水平与冠心病疾病严重程度均呈正相关(r=0.819、0.829、0.470,P<0.01)。多因素Logistic回归分析表明,合并高血压、糖尿病、高血脂、吸烟史及血清CHI3L1、IL-6、Lp-PLA 2水平升高是冠心病发生的危险因素(P<0.05)。ROC曲线分析显示,三者联合检测诊断冠心病的曲线下面积(AUC)为0.941,高于单独检测(0.900、0.883、0.757),敏感度和特异度分别为87.80%、87.50%。结论:血清CHI3L1、IL-6、Lp-PLA 2在冠心病患者中高表达,其水平与疾病严重程度呈正相关,三者联合检测可提高冠心病的诊断效能。

摘要： This study highlights the significance of supercharged NK (sNK) cells in inducing the lysis and differentiation of tumors at much higher levels compared to primary activated NK cells. sNK cells-induced higher release of growth factors, cytokines, and chemokines when compared to primary activated NK cells. When we used a similar level of IFN-γ from primary activated NK cells and sNK cells, the IFN-γ secreted from sNK cells exhibited greater potential to induce differentiation in both oral and pancreatic tumors. It is long known in the field of NK cells that primary NK cells induce significant lysis of stem-like/poorly differentiated tumors, but differentiated tumors are generally resistant to primary NK cell-mediated lysis. sNK cells, unlike primary activated NK cells, are found to highly target stem-like as well as differentiated tumors, indicating sNK cells can target not only tumors specific to NK cells but also those targeted by CD8+ T cells. Differentiation by sNK cells was inhibited less by the antibodies to IFN-γ and TNF-α when compared to that mediated by the primary activated NK cells, suggesting the role of other unexplored mechanisms in sNK cell-induced tumor differentiation. Overall, this study suggests the role of sNK cells in targeting the heterogeneous population of tumors, likely mediating the functions of both NK cells and T cells in controlling tumors, and inducing them to be effectively targeted by chemotherapy.

关键词： NOD样受体热蛋白结构域3   白细胞介素1β   白细胞介素-18   妊娠晚期   B族链球菌   感染  

摘要： 目的 探讨外周血焦亡相关因子NOD样受体热蛋白结构域3(NLRP3)、白细胞介素1β(IL-1β)、白细胞介素-18(IL-18)与妊娠晚期B族链球菌(GBS)感染的关系。方法 选取2021年7月-2023年7月本院收治的116妊娠晚期孕妇,发生GBS感染的有36例即为感染组,未发生GBS感染的有80例即为未感染组。其中GBS带菌12例(带菌组)、GBS亚临床感染16例(亚感染组)、绒毛膜羊膜炎8例(羊膜炎组)。采用酶联免疫吸附试验(ELISA)法检测血清中NLRP3、IL-1β、IL-18的表达水平。ROC曲线分析血清NLRP3、IL-1β、IL-18对妊娠晚期GBS感染的诊断价值。多因素Logistic回归分析影响妊娠晚期GBS感染的因素。结果 果与未感染组相比,感染组患者血清中NLRP3、IL-1β、IL-18水平显著升高(P<0.05)。与带菌组、亚感染组相比,羊膜炎组患者血清中NLRP3、IL-1β、IL-18水平显著升高(P<0.05)。与单独诊断相比,血清NLRP3、IL-1β、IL-18联合诊断妊娠晚期GBS感染的AUC显著升高(Z_(NLRP~LRP+1L-1β+1L-18)=2.302,P=0.021;Z_(NLRP~LRP+1L-1β+1L-18)=2.576,P=0.010;Z_(NLRP~LRP+1L-1β+1L-18)=3.477,P=0.001)。NLRP3(OR=2.458)、IL-1β(OR=1.365)、IL-18(OR=3.258)均为妊娠晚期GBS感染的危险因素(P<0.05)。结论 NLRP3、IL-1β、IL-18水平在妊娠晚期GBS感染患者血清中升高,三者联合对妊娠晚期GBS感染的发生具有较高诊断价值。

摘要： Background Results of the DRESS-PS trial showed that a tapering strategy with TNF inhibitors is non-inferior to continuation of the same TNF inhibitor dose for up to 12 months in patients with psoriatic arthritis and axial spondyloarthritis. This study aimed to describe the effectiveness of TNF inhibitor tapering for up to 24 months in patients who participated in the DRESS-PS trial. Methods This study was a 12-month observational extension of the original 12-month, open-label, non-inferiority DRESS-PS trial conducted at the Sint Maartenskliniek, Nijmegen and Woerden, the Netherlands. Patients aged 16 years and older with psoriatic arthritis or axial spondyloarthritis and stable low disease activity for at least 6 months participated in the original DRESS-PS trial. Patients were randomly assigned to either a treat-to-target tapering strategy (the intervention group), which involved extending the interval between TNF inhibitor doses, resulting in doses of 100%, 66%, 50%, or 0% of the defined daily dose, or to a treat-to-target strategy without tapering (the control group). All patients who participated in the DRESS-PS trial were eligible to participate in this extension study, in which treat-to-target tapering was allowed for all patients, and treatment decisions were made through shared decision making between physicians and patients. The primary outcome was the difference between the original intervention and control groups in the proportion of patients with low disease activity at 24 months; this difference (adjusted for stratification factors at randomisation) was compared, without and with imputation, with the prespecified non-inferiority margin of 20% from the original DRESS-PS trial, and non-inferiority was determined from the adjusted 95% CIs. There was no involvement of people with lived experience of psoriatic arthritis or axial spondyloarthritis in the design, recruitment, conduct, analysis, or reporting of this extension study. The DRESS-PS trial was regi

关键词： lichen amyloidosis   nemolizumab   IL   interleukin   JAK   Janus kinase   LA   lichen amyloidosis  

摘要： Introduction Lichen amyloidosis (LA) is a subtype of primary localized cutaneous amyloidosis, clinically characterized by persistent pruritic, hyperkeratotic papules most commonly affecting the shins, forearms, and occasionally the trunk. Histolog...

关键词： frailty   lung transplant   anemia   epigenetic age   telomere   CI   confidence interval   CpG   cytosine-phosphate-guanine   FFP   Fried Frailty Phenotype   IL   interleukin   IQR   interquartile range   IRB   institutional review board   RBC   red blood cell   SPPB   Short Physical Performance Battery   TBS-seq   targeted bisulfite sequencing  

摘要： Frailty is a syndrome of vulnerability to stressors linked to worse outcomes before and after lung transplantation. However, the biological basis of this association is unknown. Biological correlates of aging include epigenetic reprograming, chronic inflammation, telomere dysfunction, and anemia. We hypothesized that these aging-associated biological processes would be associated with frailty in lung transplant recipients. In a nested case-control study, we compared 43 lung transplant recipients who were frail pretransplant and posttransplant with 43 nonfrail matched controls. We quantified peripheral blood leukocyte epigenetic aging (Horvath) and longevity (GrimAge) clocks, telomere length, cytokine profiles, and hemoglobin before transplant. Epigenetic clocks were correlated with age but not frailty. However, we observed hypermethylation of multiple gene pathways, including hedgehog signaling and angiogenesis, and associated decreased levels of plasma cytokines in frail recipients. Frailty was also associated with telomere dysfunction and anemia. Overall, telomere dysfunction and anemia of chronic disease were most linked to frailty in this cohort, whereas epigenetic aging and chronic inflammation were not. Understanding the heterogeneity of aging syndromes may help target interventions in frail lung transplant recipients.

关键词： Acute exacerbation of bronchial asthma   Diagnostic value   ECP   FeNO   IL-4   Lung function   Periostin  

摘要： Objective This study aimed to analyze the diagnostic value of fractional exhaled nitric oxide (FeNO), periostin , interleukin (IL)-4, and eosinophil cationic protein (ECP) in patients with acute exacerbation of bronchial asthma (AEBA) and their relationship with lung function. Methods Ninety-six bronchial asthma patients admitted to our hospital from January 2020 to January 2021 were collected and divided into two groups: acute exacerbation group ( n = 55) and non-acute-exacerbation group ( n = 41). Pulmonary function indices and serum levels of FeNO, IL-4, periostin , ECP, and EOS % were determined. Pearson correlation analysis was used to analyze the relationships between these biomarkers and pulmonary function indices. A receiver operating characteristic (ROC) curve was applied to assess the diagnostic value of these biomarkers for AEBA. Results The acute-exacerbation group showed lower percentage of predicted values of peak expiratory flow (PEF %pred), forced expiratory volume in 1 s (FEV1 %pred), and forced vital capacity (FVC %pred) while higher levels of FeNO, IL-4, periostin , ECP, and EOS compared to the non-acute-exacerbation group. Pearson correlation analysis indicated that FeNO, IL-4, periostin , and ECP levels were negatively correlated with PEF %pred, FEV1 %pred, and FVC %pred, and positively correlated with EOS %. ROC curve analysis revealed that these biomarkers had high predictive value for AEBA. Conclusions FeNO, IL-4, periostin, and ECP levels are negatively correlated with pulmonary function indices (PEF %pred, FEV1 %pred, and FVC %pred) and positively correlated with EOS %. These biomarkers have high predictive value for AEBA.

关键词： IL-18 binding protein   Ulcerative colitis   dual single-atom catalyst   engineered probiotic bacterium   oral delivery  

摘要： Ulcerative Colitis (UC) involves a complex pathological process characterized by excessive reactive oxygen species (ROS) production at lesion sites and gut microbiota dysregulation. Conventional therapies are often limited by their inability to concurrently address oxidative stress, immune dysregulation, and microbial imbalance. Herein, we developed an integrated bionanoplatform (DEI) by conjugating dual single-atom catalysts (DACs) with an engineered probiotic strain, Nissle 1917 (EcN). This EcN was genetically modified to stably express interleukin-18 binding protein (IL-18BP). The DACs effectively scavenge ROS in intestinal tissues via multienzyme mimetic activities, while IL-18BP neutralizes pro-inflammatory cytokines to modulate the inflammatory milieu. Orally administered, the engineered EcN delivers and retains the DACs within the intestine, significantly enhancing ROS neutralization. Concomitantly, the DACs augment colonization of the engineered EcN, thereby amplifying its therapeutic efficacy. In a dextran sulfate sodium-induced mouse colitis model, DEI effectively mitigated colitis symptoms, attenuated inflammation, and restored the abundance and diversity of the intestinal microbiota, promoting intestinal homeostasis. This multifunctional bionanoplatform thus offers a promising synergistic strategy for UC treatment by integrating ROS scavenging, immune modulation, and microbiota restoration.