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关键词： 阻塞性睡眠呼吸暂停低通气综合征   儿童   低温等离子消融术   T细胞亚群   细胞免疫功能  

摘要： 目的:探讨低温等离子消融术治疗儿童阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的疗效及安全性。方法:选取2022年3月至2024年1月在新疆维吾尔自治区人民医院就诊的80例OSAHS患儿,随机分为腺样体刮除-扁桃体剥离组、等离子消融组,分别接受鼻内窥镜下腺样体刮除术^(+)双侧扁桃体剥离术、鼻内窥镜下低温等离子消融术。比较两组的疗效。结果:等离子消融组临床治疗总有效率优于腺样体刮除-扁桃体剥离组(P<0.05)。等离子消融组患儿的手术时间、术中出血量、术后疼痛时间、住院时间均优于腺样体刮除-扁桃体剥离组(P<0.05)。两组术后的Ig A、Ig G、Ig M水平差异不显著(P>0.05)。两组术后的CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)水平差异不显著(P>0.05)。等离子消融组术后疼痛等级优于腺样体刮除-扁桃体剥离组(P<0.05)。等离子消融组并发症发生率优于腺样体刮除-扁桃体剥离组(P<0.05)。结论:低温等离子消融术对OSAHS儿童T细胞亚群及细胞免疫功能无显著不良影响;该术式可缩短手术时间、术后疼痛持续时间及住院时间,减少术中出血量,降低患儿疼痛等级与并发症发生率。

关键词： bone marrow transplantation   breast cancer   cardiovascular disease   epigenetics   inflammaging   inflammation   immune-oncology   ischemia   myelopoiesis   peripheral arterial disease   peripheral vascular disease   reverse cardio-oncology   CLP   common lymphoid progenitor   CMP   common myeloid progenitor   CVD   cardiovascular disease   GMP   granulocyte-macrophage progenitor   HLI   hind limb ischemia   HSC   hematopoietic stem cell   HSPC   hematopoietic stem and progenitor cell   IL   interleukin   MDP   monocyte/dendritic cell progenitor   MI   myocardial infarction   PAD   peripheral artery disease   scRNAseq   single-cell RNA sequencing   Treg   regulatory T cell  

摘要： Background Patients with peripheral artery disease have an increased risk of cancer development. Aging-associated changes in hematopoietic stem and progenitor cells (HSPCs), including inflammation and increased myelopoiesis, are implicated in both cardiovascular disease and cancer, but their contributions to cardiovascular disease–driven tumor progression are unclear. Objectives This study sought to study tumor growth after peripheral ischemia and consequent changes within the HSPC bone marrow compartment to uncover mechanisms through which altered hematopoiesis promotes cancer. Methods Mammary cancer (E0771) growth was monitored in C57BL/6J mice after hind limb ischemia (HLI) or sham surgery. The tumor immune microenvironment, circulatory immune cells, and HSPC compartment were assessed by flow cytometry. Next-generation single-cell RNA and assay for transposase-accessible chromatin sequencing of bone marrow progenitors was performed to assess the distinct and synergistic transcriptomic and epigenetic changes of cancer and peripheral ischemia. The functional impact on tumor progression and persistence of ischemia-induced epigenetic reprogramming of HSPCs and their myeloid progeny was examined by bone marrow transplantation. Results Peripheral ischemia increased monocyte and neutrophil output at the expense of lymphocytes, driven by a shift toward CD150 hi myeloid-biased hematopoietic stem cells. This was associated with accelerated cancer growth and enrichment of tumors with myeloid cells (monocytes, macrophages, neutrophils) and regulatory T cells. Increased myelopoiesis was also supported by sequencing analyses showing HLI and tumor-induced transcriptional and epigenetic enrichment for inflammatory (NLRP3 inflammasome) and aging-associated neogenin-1, thrombospondin-1) signatures in subsets of monocyte/dendritic progenitors. HLI-accelerated tumor growth and myeloid-skewing was transmissible via bone marrow transplantation, indicating long-term reprogramming of in

关键词： 甲状腺癌   甲状腺髓样癌   流式细胞术   定量PCR法   新靶点  

摘要： 目的:探讨不同类型甲状腺癌患者体内IL-9来源细胞及分布特点。方法:选取2021年3月—2023年12月甲状腺乳头状癌22例和甲状腺髓样癌8例,以同期30例健康体检者为对照组,收集术前、术后7天甲状腺癌患者及对照组血液标本,流式细胞术检测外周血单个核细胞(PBMC)中IL-9表达;ELISA法测定外周血清中细胞因子IL-13、IL-4、IL-33、IL-25、IL-1β、IL-9、IL-21水平;荧光定量PCR测定血细胞PU.1、SMAD2、TGF-β、STAT3 mRNA水平。收集术中甲状腺癌组织及癌旁组织标本,荧光定量PCR法检测组织中IL-25、IL-33、IL-1β、IL-13、RORα及IL-9的mRNA表达水平,免疫荧光染色分析癌组织及癌旁组织中IL-9的表达状况。结果:流式细胞检测结果显示,产IL-9源的T细胞(Th9细胞)分布频率在甲状腺乳头状癌明显高于甲状腺髓样癌,且甲状腺髓样癌高于对照组,甲状腺癌患者术后均较术前显著上升;而产IL-9的二型固有淋巴细胞(ILC2细胞)在各组间分布无明显差异。甲状腺癌患者术前血清IL-9、IL-33、IL-25、IL-1β、IL-4、IL-21水平均显著高于对照组,术后血清IL-9、IL-4水平较术前明显升高,而IL-33、IL-25水平较术前显著下降。定量PCR结果显示,对照组Th9相关调控因子PU.1、SMAD2、TGF-β、STAT3的mRNA表达水平最低,且甲状腺癌患者术后较术前表达显著升高。癌组织定量PCR检测结果表明,甲状腺乳头状癌和甲状腺髓样癌组织中IL-25、IL-33 mRNA表达水平均显著高于癌旁组织,且甲状腺髓样癌组织显著高于乳头状癌组织,而IL-9、IL-1βmRNA表达水平相反;组织免疫荧光染色结果证明,癌组织IL-9表达水平较癌旁组织显著降低,且IL-9主要存在于CD4+T细胞。结论:甲状腺癌患者体内参与抗肿瘤作用的IL-9主要来源于Th9,且其分布可能与甲状腺癌的恶性程度相关,IL-9有望成为甲状腺癌患者诊断和治疗的新靶点。

关键词： Perforin   CD8   T Cells   Inflammatory Bowel Disease   Depression   CXCL9   CSF   cerebrospinal fluid   DSS   dextran sulfate sodium   ER   endoplasmic reticulum   FBS   fetal bovine serum   GzmB   granzyme B   IBD   inflammatory bowel disease   IFN   interferon   PBS   phosphate-buffered saline   QIDS   Quick Inventory of Depressive Symptomatology   RNA-seq   RNA sequencing   SCCAI   Simple Clinical Colitis Activity Index   siRNA   small interfering RNA   UC   ulcerative colitis   WT   wild type  

摘要： Background & Aims Approximately 25.2% of patients with inflammatory bowel disease (IBD) suffer from psychological disorders, particularly depression. Recent studies have indicated a close relationship between intestinal immunity and brain disorders. Methods We performed transcriptome analysis and immunofluorescence staining of colonic samples from patients with IBD. The role of perforin generated by colonic CD8 + T cells in IBD-induced depression was investigated in dextran sulfate sodium– and CD8 + T-cell transfer-induced colitis by using Prf1 -EGFP reporter and Prf1 knockout mice. Results In this study, we revealed a significant correlation between depressive symptom severity and perforin production in CD8 + T cells in both patients with IBD and mice with colitis. Moreover, perforin deficiency in CD8 + T cells mitigated both inflammation and depressive-like behaviors in mice with colitis. Mechanistically, perforin and granzyme B were found to stimulate the expression of CXCL9 in colonic epithelial cells. CXCL9 was shown to be released into the circulation and to enter the hippocampus, where it induced endoplasmic reticulum stress in hippocampal neurons through the CXCR3-HSPA5 axis. This cascade of events subsequently was found to exacerbate depression. Neutralizing CXCL9 in vivo alleviated depression but had no effect on colitis in mice. Conclusions Perforin generated by colonic CD8 + T cells promotes intestinal epithelial cell CXCL9 production, which leads to neuronal endoplasmic reticulum stress in hippocampus and induces depression in IBD.

关键词： 二甲双胍   利拉鲁肽   2型糖尿病   疗效   炎性因子  

摘要： 目的评估二甲双胍联合利拉鲁肽治疗2型糖尿病的效果及对血清炎性因子水平的影响。方法选取96例2型糖尿病为研究对象,应用随机数字表法将患者分为对照组(n=48例)和观察组(n=48例)。对照组患者应用二甲双胍单药治疗,观察组患者应用二甲双胍+利拉鲁肽联合治疗;评估两组患者的血糖水平、炎性因子水平,统计用药期间不良反应发生率。结果观察组治疗有效率高于对照组(P<0.05)。治疗前,两组患者血糖水平比较差异无统计学意义(P>0.05);治疗后,两组患者血糖水平比较差异具有统计学意义(P<0.05),且观察组低于对照组(P<0.05)。治疗前,两组患者血清炎性因子水平比较差异无统计学意义(P>0.05);治疗后,两组患者血清炎性因子水平明显低于治疗前(P<0.05),且观察组低于对照组(P<0.05)。观察组用药后不良反应发生率低于对照组,但两组患者比较差异无统计学意义(P>0.05)。结论2型糖尿病患者应用二甲双胍联合利拉鲁肽治疗具有较高的安全性和有效性,对于调控血糖水平、减轻机体炎性因子水平具有积极的临床意义。

摘要： PURPOSE:T cell stemness is important for anti-tumor immunity. The presence in tumor draining lymph node and tumor of stem-like memory T cells (TSCM) and T cells expressing the transcription factor TCF1, critical in T cell self-renewal, are associated with improved response to immune checkpoint inhibitors. METHODS:We studied the effects of the tumor-targeting immunocytokine PDS01ADC (NHS-IL12) on peripheral T cell stemness in murine hosts and in patients with advanced solid tumors. TSCM and expression of the murine T cell stemness markers SCA1 (Ly6a) and Tcf7 were evaluated in naïve and tumor-bearing mice receiving murine PDS01ADC (NHS-muIL12). Peripheral blood from patients treated in a clinical trial with PDS01ADC was analyzed for TSCM and expression of TCF1 on T cell subsets. RESULTS:NHS-muIL12 treatment in naïve mice increased SCA1+ peripheral T cells with stem-like phenotypes and promoted tumor infiltration of CD8+ T cells displaying increased stemness. In patients with advanced solid tumors, PDS01ADC treatment increased peripheral CD8+ and CD4+ TSCM frequencies and effector memory T cells expressing TCF1, with greater increases associated with disease control. Most peripheral TSCM were negative for PD-1 and TIGIT throughout treatment, suggesting their quiescence and self-renewal capacity. Expanded TCF1-negative effector memory CD8+ T cells expressed PD-1 with increased intensity of granzyme B, indicating an activated, cytotoxic state. CONCLUSIONS:PDS01ADC treatment in patients with advanced solid tumors boosts peripheral T cells with stem-like characteristics, correlating with disease stabilization. Further studies combining PDS01ADC with other immunotherapies to synergize with this peripheral burst of T cell stemness are warranted.

关键词： 乔松素   TLR4/NF-κB/NLRP3信号通路   IL-1β   关节软骨细胞   焦亡  

摘要： 目的 观察乔松素(Pin)抑制Toll样受体4(TLR4)/核因子κB(NF-κB)/NOD样受体蛋白3(NLRP3)信号通路对白细胞介素1β(IL-1β)诱导的关节软骨C-20/A4细胞焦亡的影响。方法 将人软骨C-20/A4细胞分为对照组、IL-1β组(50 ng/mL IL-1β)、Pin低浓度组(50 ng/mL IL-1β+50 mg/L Pin)、Pin中浓度组(50 ng/mL IL-1β+100 mg/L Pin)、Pin高浓度组(50 ng/mL IL-1β+200 mg/L Pin)、Pin高浓度+脂多糖(LPS)组(50 ng/mL IL-1β+200 mg/L Pin+2μg/mL LPS),分别进行相应处理。逆转录实时定量聚合酶链式反应(RT-qPCR)检测焦亡基因IL-18、IL-1β、半胱天冬氨酸蛋白酶1(Caspase-1)mRNA表达;流式细胞仪检测细胞焦亡情况;CCK-8法检测细胞增殖活力;蛋白免疫印迹法(Western blot)检测细胞中p-NF-κB p65、NF-κB p65、TLR4、NLRP3、IL-18、IL-1β、Caspase-1蛋白表达;酶联免疫吸附法(ELISA)检测细胞上清液IL-18、IL-6水平。结果 与对照组比较,IL-1β组细胞增殖率降低,焦亡率、细胞上清液IL-18、IL-6水平、焦亡基因IL-18、IL-1β、Caspase-1 mRNA表达及p-NF-κB p65/NF-κB p65、TLR4、NLRP3、IL-18、IL-1β、Caspase-1蛋白表达均升高(均P<0.05);与IL-1β组比较,Pin低、中、高浓度组细胞增殖率均升高,焦亡率、细胞上清液IL-18、IL-6水平、焦亡基因IL-18、IL-1β、Caspase-1 mRNA表达及p-NF-κB p65/NF-κB p65、TLR4、NLRP3、IL-18、IL-1β、Caspase-1蛋白表达均降低(均P<0.05);与Pin高浓度组比较,Pin高浓度+LPS组细胞增殖率降低,焦亡率、细胞上清液IL-18、IL-6水平、焦亡基因IL-18、IL-1β、Caspase-1 mRNA表达及p-NF-κB p65/NF-κB p65、TLR4、NLRP3、IL-18、IL-1β、Caspase-1蛋白表达均升高(均P<0.05)。结论 Pin可能通过抑制TLR4/NF-κB/NLRP3信号通路减少IL-1β诱导的关节软骨C-20/A4细胞焦亡。

关键词： LTR   Lung Transplant Recipients   AMR   antibody-mediated rejection   DSA   Donor-Specific Antibodies   TPE   therapeutic plasma exchange   MFI   Mean Fluorescence Intensity   Lung transplant   Rejection   HLA antibodies   Serum dilution   Plasma exchange  

摘要： Purpose Antibody-Mediated Rejection (AMR) due to HLA donor-specific antibodies (DSA) is associated with poor outcomes in lung transplant recipients (LTR). AMR treatment using therapeutic plasma exchange (TPE) improves clinical outcomes in LTR. The objective of this study was to assess the clinical utility of 1:16 serum dilution HLA antibody test results as a predictor of response to TPE for de novo DSA (dnDSA) levels and AMR treatment in LTR. Methods A retrospective analysis of 32 LTR diagnosed with AMR due to dnDSA and treated with TPE was performed at Mayo Clinic (n = 18) and Temple University Hospital (n = 14). HLA antibodies were detected by Luminex single antigen beads assay. Mean Fluorescence Intensity (MFI) levels were measured in undiluted and 1:16 diluted sera before the 1st and after the 5th TPE session. Statistical analysis was performed using GraphPad PRISM software. Results Of 32 patients, 14 and 18 patients were diagnosed with early (< 3 months post-transplant) and late (6 months – 3 years post-transplant) AMR respectively. All patients, except one, had HLA Class II dnDSA (97%). In addition, 9/14 (64.2%) and 3/18 (16.6%) of LTR with early and late AMR respectively had HLA class I dnDSA. The MFI for all positive dnDSA in 1:16 diluted sera collected before 1st TPE demonstrated a significant correlation with MFI in undiluted sera collected after 5th TPE in both early (R 2 = 0.8786) and late (R 2 = 0.9045) AMR post-transplant. In addition, MFI in 1:16 diluted pre TPE sera correlated with better overall LTR survival following TPE (p = 0.001). Conclusion The MFI of 1:16 serum dilution before 1st TPE may be utilized as a surrogate to predict response to TPE for AMR treatment and overall survival in LTR.

关键词： 运脾宣肺通窝汤   孟鲁司特   西替利嗪   儿童变应性鼻炎   哮喘  

摘要： 目的观察运脾宣肺通窍汤联合孟鲁司特与西替利嗪治疗儿童变应性鼻炎合并哮喘对血清白细胞介素-17(IL-17)、白细胞介素-33(IL-33)、微小RNA-31(miRNA-31)水平的影响。方法选取110例儿童变应性鼻炎合并哮喘患者为对象,采用抽签法分为两组。西药组采用孟鲁司特联合西替利嗪治疗,综合组在西药组基础上联合运脾宣肺通窍汤加减治疗。比较两组中医证候评分、哮喘控制调查问卷(ACT)评分、症状评分及miRNA-31、黏附分子CD44(CD44)mRNA、特异性免疫球蛋白G4(sIgC4)、白细胞介素-8(IL-8)、IL-17、IL-33水平,统计两组不良反应发生率。结果两组治疗后ACT评分高于治疗前,且综合组高于西药组(P<0.05);两组治疗后中医证候评分低于治疗前,且综合组低于西药组(P<0.05);两组治疗后连续喷嚏个数、鼻痒、鼻堵及每日擦鼻次数评分低于治疗前,且综合组低于西药组(P<0.05);两组治疗后miRNA-31、CD44mRNA低于治疗前,且综合组低于西药组(P<0.05);两组治疗后sIgC4高于治疗前,且综合组高于西药组(P<0.05);两组治疗后IL-8、IL-17、IL-33低于治疗前,且综合组低于西药组(P<0.05);两组不良反应发生率比较,无差异(P>0.05)。结论运脾宣肺通窝汤联合孟鲁司特与西替利嗪治疗儿童变应性鼻炎合并哮喘可降低miRNA一31、CD44mRNA表达水平,减轻症状,且安全性高。

关键词： hMHC mice   SARS-CoV-2   COVID-19   Humanization   Transcriptome  

摘要： Background The ongoing COVID-19 pandemic caused by SARS-CoV-2 remains a critical global health priority, with persistent socioeconomic ramifications despite its reclassification from Public Health Emergency of International Concern (PHEIC) status. While humanized major histocompatibility complex (hMHC) murine models have been extensively utilized in oncological research, their application in virological studies-particularly for coronavirus pathogenesis-remains *** This study systematically characterized immune responses in SARS-CoV-2-challenged hMHC mice lung tissues through comparative transcriptomic profiling, combined with functional enrichment and PPI network *** Key findings demonstrate that hMHC mice exhibit enhanced immunological activation relative to wild-type controls, particularly in IFN-gamma signaling pathways and neutrophil mobilization dynamics that closely parallel human post-vaccination responses. Comparative analysis with human whole blood RNA-seq datasets revealed that hMHC mice exhibit both high reproducibility in transcriptomic profiles and significant similarity to human immune responses across innate and adaptive *** These results confirm that the hMHC murine model can serve as an effective platform for vaccine research, providing a theoretical foundation for the application of humanized MHC mice and offering new insights into viral infection mechanisms and the development of novel vaccines.