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关键词： dupilumab   monoclonal gammopathy   primary mucinosis   scleromyxedema   IL   interleukin   IVIG   intravenous Immunoglobulin   SMX   scleromyxedema  

摘要： Histopathologic examination of the biopsy sample. Histopathologic features of scleromyxedema. A- C, Abundant mucin deposition within papillary and reticular dermis ( A-C, Hematoxylin-eosin stain; original magnifications: A, 20×; B, 50×; C, 100×). ...

摘要： The author regrets that the image of KPC in shATG9A group in Fig. 4 D was duplicated with the image of Panc02 in OE+ICB group of Fig. 5F. The image of Panc02 in NC group of Fig. 4D was duplicated with the image of KPC in NC group of Fig. 5E. Upon ...

关键词： AAV   adeno-associated virus   ABM   Ascl1, Brn2 and Myt1l   AD   Alzheimer disease   ADRC   adipose-derived regenerative cell   AI   artificial intelligence   ALS   amyotrophic lateral sclerosis   AMD   age-related macular degeneration   ASO   antisense oligonucleotide   ATMP   advanced therapy medicinal product   BBB   blood–brain barrier   BM   basement membrane   BDNF   brain-derived neurotrophic factor   BP-NCD   branched polyethyleneimine coated nitrogen-enriched carbon dots   BrdU   Bromodeoxyuridine   CD-AOF   chemically defined animal origin–free   CiPSC   chemically induced pluripotent stem cell   CNS   central nervous system   2D   2-dimensional   3D   3-dimensional   DMD   Duchenne muscular dystrophy   ECM   extracellular matrix   EGR2   early growth response protein 2   EMT   epithelial-to-mesenchymal transition   EPI   epiblast   ESC   embryonic stem cell   EV   extracellular vesicle   FAD   familial Alzheimer disease   FDA   US Food and Drug Administration   FGF   fibroblast growth factor   FNLM   FH-peptide-modified neutrophil-mimicking membrane   GMT   GATA4, MEF2C and TBX5   HCV   hepatitis C virus   HDF   human dermal fibroblast   hESC   human embryonic stem cell   HFF   human foreskin fibroblast   HIP   hypoimmune induced pluripotent stem cell   hiPSC   human induced pluripotent stem cell   hPSC   human pluripotent stem cell   HLA   human leukocyte antigen   HSC   hematopoietic stem cell   hUC   human urine cell   iCM   induced cardiomyocyte   ICM   inner cell mass   iHep   induced hepatocyte   IL   interleukin   ILC   innate lymphoid cell   iN   induced neuron   iPSC   induced pluripotent stem cell   iPSC-CM   induced pluripotent stem cell–derived cardiomyocyte   IRD   inherited retinal disease   LQTS   long-QT syndrome   MEF   mouse embryonic fibroblast   MG   Müller glia   MI   myocardial infarction   ML   machine learning   miR   microRNA   MPS   microphysiological system   MSC   mesenchymal stem cell   MST   MYOCD, SMAD6 and TBX20   MT   MEF2C and TBX5   mtDNA   mitochondrial DNA   MuSC   muscle stem cell   NCC   neural crest cell   NeuroD1   neuronal differentiation 1   NK   natural killer   NMJ   neuromuscular junction   NSC   neural stem cell   OCA   oculocutaneous albinism   OSK   Oct3/4, Sox2, Klf4   OSKM   Oct3/4, Sox2, Klf4, c-Myc   OPC   oligodendrocyte pro  

摘要： Recent advancements in cell and tissue biology have fundamentally changed our understanding of cellular behavior, revealing that both stem and nonstem cells exhibit remarkable plasticity and adaptability. This discovery has paved the way for revolutionary medical drug therapies that leverage cell and tissue reprogramming to repair or regenerate damaged tissues, offering new hope for conditions that were once considered irreversible. Tissue reprogramming involves the activation of specific molecular pathways to convert the function of residual tissue to compensate for the loss of tissue function to aging, trauma, or disease processes. By targeting these pathways, emerging drugs can promote regenerative processes, enabling the restoration of tissue function lost due to aging, injury, or disease. These therapies have shown promising results in preclinical studies addressing a wide range of diseases. Unlike traditional treatments, which focus primarily on managing symptoms, tissue reprogramming therapies offer a dynamic approach that can fundamentally alter cellular states, leading to functional recovery. This review explores the current state of cell and tissue reprogramming, highlighting its potential applications in regenerative medicine and the challenges that must be addressed for successful clinical translation. As our understanding of cellular plasticity continues to evolve, these innovative therapies stand at the forefront of a new era in medicine, with the potential to transform treatment paradigms and significantly improve patient outcomes across a wide range of conditions. Significance Statement Breakthrough technologies have transformed our understanding of cell and tissue biology, uncovering that cells and tissues possess remarkable adaptability and fluidity in their roles. This revelation has opened up exciting possibilities in regenerative medicine, where emerging drug therapies aim to harness and reprogram cells to repair or regenerate damaged tissues. A

关键词： 大肠杆菌   沙门氏菌   翁芩复方   细胞因子  

摘要： 为了探讨翁芩复方（WQ）对雏鸭感染禽大肠杆菌（E. coli）或沙门氏菌（Sal）的预防效果，本研究采用肉汤二倍稀释法体外测定最小抑菌浓度（MIC）和最小杀菌浓度（MBC）；不同剂量WQ预处理雏鸭7 d后，气囊注射E. coli或口服感染Sal，通过比较日增重和存活率评价WQ对感染雏鸭的预防效果，RT-PCR和细菌计数检测细菌入侵和定植肝脏程度，RT-qPCR检测十二指肠白介素6（IL-6）、白介素10（IL-10）表达。结果表明：WQ对E. coli和Sal有明显的体外抑菌效果；WQ干预后E. coli和Sal感染雏鸭的存活率提高；WQ降低E. coli诱导的IL-6，且恢复E. coli抑制的IL-10至正常水平；WQ组肝脏的Sal阳性率减少。以上结果表明，WQ对E. coli和Sal感染具有一定的预防效果，为临床防控该菌大规模流行提供了技术支撑。

关键词： Autoimmunity   Sex   AFAB   assigned female at birth   AIRE   autoimmune regulator   AMAB   assigned male at birth   ANA   antinuclear antibody   AR   androgen receptor   CLE   cutaneous lupus erythematosus   DC   dendritic cell   ER   estrogen receptor   GAHT   gender-affirming hormonal therapy   HIF1α   hypoxia inducible factor-1α   ILC2   innate lymphoid cell type 2   lncRNA   long noncoding RNA   MHC   major histocompatibility complex   PAR   pseudoautosomal region   pDC   plasmacytoid dendritic cell   PR   progesterone receptor   pSS   primary Sjögren syndrome   RA   rheumatoid arthritis   RNP   ribonucleoprotein   SLE   systemic lupus erythematosus   SNV   single-nucleotide variation   SS   Sjögren’s syndrome   SSc   systemic scleroderma   TGD   transgender and gender-diverse   Th17   T helper 17   TLR   toll-like receptor   Treg   regulatory T cell   XCI   X chromosome inactivation  

摘要： Autoimmune diseases result from the immune system’s inability to discriminate between self and foreign antigens, leading to development of self-reactive immune cells and autoantibodies that can cause organ damage and failure. It has long been known that many autoimmune diseases are more common in females. Although much progress has been made over the years, the exact mechanisms for this sex bias are not yet fully understood. In this review, we provide an overview and update on how chromosomes, genes, sex hormones (including gender-affirming hormone therapy), immunometabolism, and the skin can play a role in sex-biased autoimmunity. We also identify gaps in our understanding that require additional research. In an era of increased development of personalized medicine, a thorough understanding of sex bias in autoimmunity may facilitate the development of much-needed targeted therapeutics, thereby reducing the risks of broader immunosuppression and adverse effects that lead to premature termination of treatment by patients.

关键词： 禽网状内皮组织增生症病毒   囊膜蛋白gp90   原核表达   杂交瘤细胞   单克隆抗体  

摘要： 为研制禽网状内皮组织增生症病毒(Reticuloendotheliosis virus,REV)囊膜蛋白gp90单克隆抗体,试验构建重组原核表达质粒pCold-gp90,转化至感受态细胞BL21中进行蛋白诱导表达;采用纯化的gp90蛋白免疫BALB/c小鼠,通过细胞融合技术制备杂交瘤细胞,利用间接酶联免疫吸附试验(ELISA)和流式细胞分选技术筛选鉴定阳性杂交瘤细胞,并制备单克隆抗体腹水,对单克隆抗体的亚型、效价进行测定;并初步测试单克隆抗体在Western blot和间接免疫荧光试验(IFA)中检测gp90蛋白和REV中的应用效果。结果显示:REV囊膜蛋白gp90获得成功表达和纯化,获得3株能稳定分泌REV gp90单克隆抗体的阳性杂交瘤细胞株,该单克隆抗体亚型均为IgG1、Kappa,腹水效价均可达1∶64000;该单克隆抗体不仅可用于Western blot或IFA检测gp90原核表达蛋白和真核表达蛋白,还可用于IFA检测REV的TCID50效价。研究表明,成功制备的REV gp90单克隆抗体为进一步的REV检测方法建立和gp90蛋白功能研究提供了重要工具。

关键词： 四物汤   辐射   免疫损伤   PI3k-Akt-mTOR   Sirt1   淋巴细胞  

摘要： 目的探讨四物汤(Siwu decoction,SWD)对^(60)Coγ射线辐射所致小鼠免疫损伤的防护作用及机制。方法将C57BL/6J小鼠随机分为6组:对照组(Control)、模型组(Model)、四物汤低剂量组(SWD-L)、四物汤中剂量组(SWD-M)、四物汤高剂量组(SWD-H)、阳性药白藜芦醇组(resveratrol,Res),于辐照前11 d及辐照后继续给药,单次全身照射4 Gy,照射后3 d检测各指标。检测外周血象及脏器指数变化,酶联免疫吸附法(ELISA)检测血清中细胞因子γ干扰素(IFN-γ)、白细胞介素(IL)-1β、IL-2、IL-4、IL-6、IL-10、IL-17、转化生长因子-β(TGF-β)、肿瘤坏死因子(TNF)-α以及免疫球蛋白A(IgA)、IgG、IgM,补体蛋白3(C3)、C4的含量。流式细胞术检测小鼠脾脏B淋巴细胞、T淋巴细胞、NK细胞以及胸腺中T淋巴细胞;苏木精-伊红(HE)染色显示脾脏、胸腺病理损伤变化。免疫荧光染色检测辐射后脾脏组织Sirt1蛋白表达,Western blot实验检测脾脏中Sirt1,PI3K,Akt,p-Akt,mTOR蛋白含量变化。结果SWD能明显提高LYMPH%,减轻脾脏和胸腺病理损伤,流式细胞术实验结果表明,SWD能明显提高脾脏中CD19^(+)B淋巴细胞百分比,降低NK淋巴细胞百分比以及脾脏和胸腺中CD4^(+)/CD8^(+)比值。ELISA结果显示,SWD明显降低IL-1β、IL-2、IL-6、IL-17、IFN-γ、TGF-β、TNF-α的含量,以及增强抗炎因子IL-4、IL-10的含量。同时,SWD显著抑制辐射引起的IgA、IgG、IgM,C3、C4的升高。免疫荧光染色和Western blot实验结果表明,SWD能够降低PI3K、Akt、p-Akt、mTOR蛋白表达,增强Sirt1蛋白表达。结论SWD对^(60)Coγ射线辐射所致小鼠免疫损伤具有明显的预防作用,其机制可能与Sirt1-PI3k-Akt-mTOR有关。

关键词： Cystic fibrosis   Clinical trial   Cytokines   Biomarkers   Inflammation   Antibiotics   Anti-inflammatory   cf   Cystic fibrosis   cfq-r   Cystic fibrosis questionnaire-revised   cfrsd   Cf respiratory symptom diary   cftr   Cystic fibrosis transmembrane conductance regulator   criss   Chronic respiratory infection symptom score   crp   C-reactive protein   elisa   Enzyme-linked immunosorbent assay   fev1   Forced expiratory volume in 1 s   g-csf   Granulocyte colony stimulating factor   hemt   Highly-effective cftr modulator therapy   ifn-γ   Interferon-gamma   il   Interleukin   il-1ra   interleukin-1 receptor antagonist   IP-10   interferon-gamma-induced protein 10   IV   intravenous   LLOD   lower limit of detection   P. aeuruginosa   Pseudomonas aeruginosa   PEx   pulmonary exacerbation   pwCF   people with CF   RCT   randomized controlled trial  

摘要： Background: Cystic fibrosis (CF) pulmonary exacerbations are characterized by increased inflammation. The objectives of this study were to identify inflammatory biomarkers associated with 1) early clinical response to IV antibiotics (by day 7); and 2) response to the delayed use of prednisone (from day 7 to 14). Methods: This was a secondary analysis of a clinical trial evaluating the adjunctive use of prednisone in pwCF. We studied blood and sputum inflammatory markers at Day 0 that were associated with early response to IV antibiotics at Day 7 (early responder analysis). In non-responders to IV antibiotics alone, we examined biomarkers at Day 7 that were associated with response to oral prednisone at Day 14. Clinical outcomes included: 1) absolute change in ppFEV 1 ; 2) absolute change in chronic respiratory infection symptom score (CRISS); and 3) composite outcome of absolute improvement in ppFEV1 of ≥ 8 % and CRISS score decrease by ≥ 11 (early responder analysis only). Results: Higher Day 0 sputum IFN-γ and lower blood calprotectin were associated with improved Day 7 lung function response; lower Day 0 sputum IL-8 and blood eotaxin were associated with improved symptom scores. In non-responders at Day 7, higher blood eotaxin was associated with better lung function response and higher blood CRP was associated with worse symptom score response at Day 14 in those treated with prednisone versus placebo. Conclusion: Sputum and blood inflammatory markers are associated with early response to IV antibiotics and change with prednisone treatment during PEx.

关键词： CD4(+) T cells   CXCR6   IFN-γ   gut   neuroimmunomodulation   subfornical organ   white adipose  

摘要： The constitutive presence of immune cells within brain parenchyma under homeostatic conditions is debated. Recent findings by Yoshida et al . have shown that the subfornical organ harbors gut- and adipose-derived T cells that secrete IFN-γ to regulate brain homeostasis and adaptive behavior in the gut–fat–brain immune axis.

关键词： 慢性鼻窦炎   白细胞介素-6   趋化因子4   嗜酸性细胞阳离子蛋白   术后复发   预测价值  

摘要： 目的探讨慢性鼻窦炎患者血清白细胞介素-6(IL-6)、趋化因子4(CCL-4)、嗜酸性细胞阳离子蛋白(ECP)水平变化及对术后复发的预测价值。方法回顾性2021年12月—2023年12月盐城市第三人民医院收治的154例慢性鼻窦炎患者的临床资料,将其归为研究组,并以同期入院体检的60例健康人群为对照组。根据患者术后复发情况将研究组分为复发组63例和未复发组91例。比较研究组与对照组、复发组与未复发组血清IL-6、CCL-4、ECP水平。采用受试者工作特征(ROC)曲线分析血清IL-6、CCL-4、ECP水平对慢性鼻窦炎患者术后复发的预测效能。结果研究组血清IL-6、CCL-4、ECP水平均高于对照组(P<0.05)。复发组血清IL-6、CCL-4、ECP水平均高于未复发组(P<0.05)。ROC曲线分析结果显示,血清IL-6、CCL-4、ECP预测慢性鼻窦炎患者术后复发的曲线下面积分别为0.768(95%CI:0.705,0.822)、0.791(95%CI:0.731,0.844)、0.815(95%CI:0.755,0.863);敏感性分别为62.50%(95%CI:0.538,0.706)、77.94%(95%CI:0.700,0.846)、67.65%(95%CI:0.591,0.754);特异性分别为83.12%(95%CI:0.729,0.907)、74.03%(95%CI:0.628,0.834)、80.52%(95%CI:0.699,0.887)。结论慢性鼻窦炎患者血清IL-6、CCL-4、ECP水平较健康人群有明显升高趋势,其水平与术后复发有关,水平越高术后复发概率越大,临床早期检测患者血清IL-6、CCL-4、ECP水平,可有效预测患者术后复发,为临床早期预防性治疗提供参考。