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关键词： miR-21   IL-12   INF-Y   Diagnostic markers   Different stages   Breast cancer  

摘要： Studying miR-21, IL-12, and INF-Y as diagnostic markers in breast cancer stages aids in early detection and optimizing treatment for improved patient outcomes. In the current research, 150 breast cancer patients and 50 healthy controls from Baqiyatullah and Shahada Hospital underwent ELISA for IL-12 and INF-Y and real-time PCR for miR-21 expression. We examined 150 patients with BC and 50 healthy individuals. The average age was 51.56 +/- 10.16 years. 96.5% were married, with a higher family history of cancer (51.33%) in patients. IL-12 and INF-Y levels' highest mean was in stage 1 and stage 4, respectively. miR-21 gene expression was highest in stage IIIA (11.61) and lowest in stage IIIB (5.13). Significant differences in miR-21 expression, IL-12, and INF-Y levels were observed between breast cancer (BC) cases and the healthy group. The study sheds light on biomarkers critical to BC detection, including interleukin-12, interferon-gamma, and miRNA-21. The study suggests IL-12, INF-Y, and miR-21 gene expression as potential diagnostic markers for breast cancer, with strong correlations to disease grade and stage. IL-12 and INF-Y exhibit 100% sensitivity and specificity, while miR-21 shows 85% sensitivity, promising accurate detection.

关键词： Alzheimer's disease   ApoE gene polymorphism   homocysteine   cognitive dysfunction   prediction model  

摘要： Objective: This study focuses on the cognitive dysfunction in patients with Alzheimer's disease (AD), aims to in-depth analysis of the Apolipoprotein E (ApoE) gene polymorphism, homocysteine (Hcy) and the intrinsic relationship between the disease, and build accurate and effective prediction model. Methods: A total of 193 AD patients were divided into a training set (n = 135) and a validation set (n = 58) according to the ratio of 7:3. The risk factors were screened by univariate and multivariate Logistic regression in the training set, and the nomogram model was constructed. The receiver operating characteristic curve (ROC) was drawn and the calibration curve was used to evaluate the effectiveness of the model. The model was verified in the validation set, and the clinical value was evaluated by decision curve analysis (DCA). Results: The multivariate Logistic regression analysis showed that high PSQI score, elevated Hcy, ApoE epsilon 4 allele carrying, decreased folic acid, elevated hs-CRP and IL-6 were the independent risk factors for cognitive dysfunction in AD patients (p < 0.05). The nomogram model performed well in the training and validation sets for calibration and prediction, with C-index values of 0.863 and 0.769, respectively, area under ROC curve (AUC) values of 0.870 and 0.771. Conclusion: The nomogram prediction model constructed based on ApoE gene polymorphism and Hcy et al. can be used to predict the risk of cognitive dysfunction in AD patients and provide a reference basis for formulating personalized intervention plan in clinic. However, it still needs further verification by large sample and multi-center study.

关键词： microbiome   JAK inhibitors   dupilumab   cyclosporine A   topical corticosteroids   AD   atopic dermatitis   CyA   cyclosporine A   DLQI   Dermatology Life Quality Index   DUPI   dupilumab   EASI   Eczema Area and Severity Index   IgE   serum immunoglobulin E   IL   interleukin   JAK   Janus kinase   JAKi   Janus kinase inhibitors   PP NRS   Peak Pruritus Numeric Rating Scale   S. aureus   Staphylococcus aureus   TCS   topical corticosteroids   TP   time point   S/CC ratio   the ratio of the genus   Staphylococcus   to genera   Corynebacterium   and   Cutibacterium  

摘要： Atopic dermatitis is a complex disease that requires treatments addressing skin barrier disruption, inflammation, and microbial imbalance. Here, we aimed to investigate the effects of four different therapies on clinical outcomes and skin bacteriome in patients with atopic dermatitis, namely: Janus kinase inhibitors, dupilumab, cyclosporine A, and topical corticosteroids (intermittently used methylprednisolone aceponate). Samples from 60 patients were collected before treatment and after three and six months and their bacteriome diversity and composition were analyzed. All treatment groups showed significant improvement in disease severity after three months; however, only dupilumab resulted in a marked reduction in serum immunoglobulin E levels and an almost complete depletion of Staphylococcus aureus . The relative abundance of this bacterium correlated with disease severity and remained significantly lower in patients receiving dupilumab compared to those treated with cyclosporine A or topical corticosteroids. While overall bacteriome alpha diversity remained unchanged, the ratio of Staphylococcus to Corynebacterium and Cutibacterium decreased significantly after Janus kinase inhibitors as well as dupilumab treatment but remained stable with cyclosporine A and topical corticosteroids. These results indicate that addressing type 2 inflammation by targeted drugs alters the skin bacteriome towards a healthy balance, while traditional anti-inflammatory treatments have minimal impact on microbial composition.

关键词： 中性粒细胞与淋巴细胞比值(NLR)   慢性阻塞性肺疾病(COPD)   肺癌   慢性阻塞性肺疾病合并肺癌   综述  

摘要： 中性粒细胞与淋巴细胞比值（NLR) 作为一种简便、可靠的炎症生物标志物，在多种炎症性疾病和肿瘤中的临床应用备受关注。该指标通过量化中性粒细胞和淋巴细胞数量，反映了机体的免疫炎症状态。本文主要对NLR在慢性阻塞性肺疾病（COPD）合并晚期肺癌(LC）中的研究进展进行综述，旨在为临床实践提供新的诊断工具和预后评估方法及治疗参考。

关键词： tuberculosis   cytokines   TNF-alpha   IL-1 beta   nutritional status   length of stay   case-control study   mortality   inflammatory markers   host directed therapy  

摘要： Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised with pulmonary TB. We analysed 80 adults with microbiologically confirmed pulmonary TB and 40 respiratory symptom controls;four TB patients (5%) died during hospitalisation, all within 10 days of admission. Methods: A retrospective analytical case-control study was conducted at the Constanta regional TB referral centre (October 2020-October 2023). Patients with smear- or culture-confirmed TB were frequency-matched by sex, 10-year age band, and BMI class to culture-negative respiratory controls at a 2:1 ratio. The patients' serum interferon-gamma (IFN-gamma), interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), and tumour-necrosis-factor-alpha (TNF-alpha) were quantified within 24 h of admission;the neutrophil/lymphocyte ratio (NLR) was extracted from full blood counts. Independent predictors of in-hospital mortality were identified by multivariable logistic regression;factors associated with the length of stay (LOS) were modelled with quasi-Poisson regression. Results: The median TNF-alpha (24.1 pg mL(-1) vs. 16.2 pg mL(-1);p = 0.009) and IL-1 beta (5.34 pg mL(-1) vs. 3.67 pg mL(-1);p = 0.008) were significantly higher in the TB cases than in controls. TNF-alpha was strongly correlated with IL-1 beta (rho = 0.80;p < 0.001), while NLR showed weak concordance with multiplex cytokine patterns. Among the patients with TB, four early deaths (5%) exhibited a tripling of TNF-alpha (71.4 pg mL(-1)) and a doubling of NLR (7.8) compared with the survivors. Each 10 pg mL(-1) rise in TNF-alpha independently increased the odds of in-hospital death by 1.8-fold (95% CI 1.1-3.0;p = 0.02). The LOS (median 29 days) was unrelated to the

关键词： vitiligo   tissue-resident memory T cell   IL-15   CD122   ruxolitinib   AMG 714  

摘要： Vitiligo is a chronic autoimmune disorder in which melanocyte-specific CD8+ T cells destroy pigment-forming cells, producing persistent depigmented macules. Recurrence after treatment implicates tissue-resident memory T (TRM) cells that are maintained by interleukin-15 (IL-15) signaling. Here we review current insights into TRM-cell biology, summarize experimental and emerging clinical data targeting the IL-15/CD122 axis-including the ongoing Phase 2a AMG 714 trial-and discuss combination strategies with approved topical Janus kinase inhibitors such as ruxolitinib cream. Disrupting IL-15 may offer durable repigmentation with minimal systemic immunosuppression.

关键词： 哮喘   白细胞介素33   小鼠模型   炎症  

摘要： 为了探究IL-33敲低减轻小鼠哮喘模型气道炎症的作用,以期发现哮喘治疗的新靶点,收集鼠源骨髓间充质干细胞（bone marrow mesenchymal stem cell, BMMSC）,通过慢病毒将IL-33沉默质粒（si-IL-33-1#、 si-IL-33-2#、 si-IL-33-3#质粒和si-空载对照质粒）转染BMMSC,利用qRT-PCR筛选IL-33沉默质粒。利用致敏剂和激发剂相结合的方法构建哮喘小鼠模型,根据处理方案分成对照组、模型组、 BMMSC组、 BMMSC+空载组和BMMSC+IL-33敲低组。利用H-E染色、Masson染色和免疫组织化学（immunohistochemistry, IHC）等方法检测肺组织病理性改变, ELISA法检测小鼠血清中IL-33、 IL-1β和IL-6的表达量。原代BMMSC贴壁生长,细胞呈梭形或多角形;流式细胞仪检测BMMSC的表面蛋白CD90阳性率为99.30%, CD29阳性率为100.00%。而CD45和CD34的阳性率较低,分别为0.34%和1.24%。qRT-PCR结果显示, si-IL-33-3#质粒可沉默BMMSC中IL-33的表达,可作为IL-33的敲减质粒。H-E和Masson染色结果显示, BMMSC+IL-33敲低组肺部炎症细胞浸润极少,支气管上皮细胞正常。IHC结果显示, BMMSC+IL-33敲低组中α-平滑肌肌动蛋白（alpha-smooth muscle actin,α-SMA）和血管内皮生长因子（vascular endothelial growth factor B, VEGFB）的蛋白相对表达量显著低于BMMSC组和模型组（P<0.05）。ELISA结果显示, BMMSC+IL-33敲低组小鼠外周血中IL-1β、 IL-6和IL-33的表达量显著低于模型组和BMMSC组（P<0.05）。IL-33敲低后可抑制哮喘小鼠模型的炎症反应,进而阻止哮喘肺部病变。

关键词： circadian rhythm disorder   fish oil   flaxseed oil   kidney damage   signalling protein  

摘要： ObjectivesThis study set out to investigate kidney damage by examining the levels of key proteins-HIF-2 alpha, COX-2 and IFN-gamma in rats with disrupted circadian rhythms. It also explored how fish oil and flaxseed oil might influence the intensity of inflammation and its effects on kidney *** rhythm disorder model groups consisted of eight rats each. Except for the control group, other groups (circadian rhythm, flaxseed oil and fish oil groups) were exposed to an adjustable light/dark cycle for 19 days, while the control group was kept on a standard light/dark cycle. In addition to standard food and water ad libitum nutrition for 19 days in four groups, 1000 mg/kg/day flaxseed oil was given to the flaxseed oil group and 400 mg/kg/day fish oil was given to the fish oil group by gavage for 19 days. Histological lesions in tissues were evaluated by Haematoxylin-Eosin staining and using a sequential grading system. For immunohistochemical analysis, IFN-gamma, COX-2 and HIF-2 antibodies were used to evaluate the degree of immunohistochemical reactivity of the *** unequivocally plays a critical role in regulating circadian rhythms, as factors such as meal timing, nutrient composition and gut health directly influence the body's internal clock and overall rhythm stability. Omega-3 fatty acids are known to influence immune, inflammatory and neurological pathways-all of which are controlled by the circadian clock. When circadian rhythms are disrupted, key signalling proteins such as HIF-2 alpha, COX-2 and IFN-gamma become dysregulated, leading to potential kidney damage. Remarkably, treatments with fish oil and flaxseed oil have been shown to reduce inflammation markers, effectively mitigating kidney damage and offering significant anti-inflammatory benefits. These results emphasize the aptitude of incorporating fish oil and flaxseed oil into the diet as a powerful strategy to combat kidney damage and slow the pathological effects cau

关键词： HLA-E   Multiple Myeloma   NKG2A   NKG2C   NK   Immune Checkpoint  

摘要： HLA-E presenting the HLA-G leader peptide VMAPRTLFL (HLA-E [pHLA-G] ) on tumor cells plays a crucial role in suppressing natural killer(NK) and cytotoxic CD8+ T cells through NKG2A interaction. While blocking HLA-E:NKG2A is a promising immune checkpoint(IC) approach in cancer therapy, toxicity remains a major clinical concern. We developed a novel immune checkpoint inhibitor(ICI) that selectively prevents HLA-E:NKG2A interaction, a monoclonal antibody(mAb) that selectively targets the HLA-E [pHLA-G] complex, distinguishing cancerous from non-cancerous cells. In clinical bone marrow samples from multiple myeloma(MM) patients, 4D7 specifically recognized tumor-associated HLA-E-peptide complexes. Using NK cells from healthy donors, 4D7 effectively blocked the HLA-E:NKG2A interaction and enhanced NKG2A-positive NK cell activity in autologous MM cell co-cultures. Importantly, 4D7 did not inhibit NKG2C-positive NK cells, preserving their activity. Even though NKG2C also interacts with HLA-E. In MM-bearing mice treated with human NK cells, 4D7 significantly reduced tumor growth. This targeted approach activates NK cells only against tumor cells presenting HLA-E-peptide complexes, potentially minimizing toxicity compared to current NKG2A inhibitors. The development of 4D7 highlights a promising advancement in immunotherapy for hematological malignancies, offering improved outcomes for MM patients and a foundation for broader application across cancer types.

关键词： non-HLA autoantibodies   anti-angiotensin II type 1 receptor antibody   endothelin type A receptor antibody   antibody-mediated rejection   Banff classification   biopsy-based transcript diagnostics   kidney transplantation   ADPKD   autosomal dominant polycystic kidney disease   ah   arteriolar hyalinosis   AKI   acute kidney injury   AMR   antibody-mediated rejection   AT1R-Ab   angiotensin II type 1 receptor antibody   Bx   biopsy   CAKUT   congenital anomalies of the kidneys and urinary tracts   cg   glomerular basement membrane double contours   ci   interstitial fibrosis   ct   tubular atrophy   cv   vascular fibrous intimal thickening   DCD   donor after cardiac death   DSA   donor-specific antibody   eGFR   estimated glomerular filtration rate   ETAR-Ab   endothelin type A receptor antibody   g   glomerulitis   hAMR   histological antibody-mediated rejection   HLA   human leukocyte antigen   i   intersitial inflammation   IFTA   interstitial fibrosis and tubular atrophy   i-IFTA   inflammation in the area of interstitial fibrosis and tubular atrophy   IQR   interquartile range   IRRAT   injury-repair response–associated transcripts   KTR   kidney transplant recipient   mAMR   molecular antibody-mediated rejection   MFI   mean fluorescence intensity   MMDx   molecular microscope diagnostic system   MVI   microvascular inflammation   NA   not applicable   pAMR   probable antibody-mediated rejection   ptc   peritubular capillaritis   ptcml   peritubular capillary basement membrane multilayering   SAB   single antigen bead   SCr   serum creatinine   SD   standard deviation   t   tubulitis   TCMR   T-cell-mediated rejection   ti   total inflammation   TMA   thrombotic microangiopathy   TPL   transplantation   ULN   upper limit of normal   UPCR   urinary protein-to-creatinine ratio   v   intimal arteritis  

摘要： Some kidney allograft biopsies with microvascular inflammation (MVI) – a hallmark of antibody-mediated rejection (AMR) – lack evidence of anti-human leukocyte antigen (HLA) donor-specific antibodies (DSA). In these cases, alternative mechanisms of allograft injury may play a role, such as non-HLA angiotensin II type 1 receptor (AT1R) or endothelin type A receptor (ETAR) autoantibodies. In this single-center study, 196 biopsies were evaluated by histology and biopsy-based transcript diagnostics. Anti-HLA antibodies, AT1R-, and ETAR-Ab serology were determined at the time of biopsy. Of 61 histological AMR, 29 (48%) were identified as molecular AMR (mAMR); of 24 MVI, DSA negative, C4d negative biopsies, 11 (46%) biopsies were mAMR. Additionally, 6 (16%) of 37 probable AMR biopsies were mAMR. The AT1R-/ETAR-Ab concentration did not differ among histological categories or across different levels of molecular scores. However, biopsies with mAMR had higher concentrations of AT1R-Ab (p=0.09) and ETAR-Ab (p=0.02) compared to biopsies with no molecular rejection. The presence of non-HLA autoantibodies did not affect the outcome. Biopsies with MVI at/above threshold showed higher hazard (HR 2.09, 95% CI [0.90 to 4.86], p=0.09) of composite endpoint (allograft failure or eGFR <15ml/min). Non-HLA autoantibodies reflect molecular AMR injury, but their clinical utility is likely limited.