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关键词： 骨结核   T细胞亚群   细胞因子   免疫紊乱   抗结核   结核杆菌  

摘要： 目的 探讨非骨结核与骨结核人群以及骨结核患者治疗前后机体T细胞亚群和相关细胞因子差异及原因分析。方法 整理2022年1月至2024年8月于南京市中西医结合医院骨伤科住院并完成T细胞亚群及相关细胞因子检测的患者资料，共纳入分析837例，按病种分为骨结核组168例，非骨结核组669例，根据住院期间定期检测的T细胞亚群及相关细胞因子指标，对比非骨结核与骨结核人群以及骨结核患者治疗前后上述指标的差异。结果 与非骨结核组相比，骨结核组表现为Th1、Th17、Treg水平降低，(Th1+Th17)/Treg升高，白介素-1β(IL-1β)、白介素-4(IL-4)、白介素-5(IL-5)、白介素-8(IL-8)、白介素-10(IL-10)、白介素-12p70(IL-12P70)、干扰素-α(INF-α)水平明显降低，差异有统计学意义(P<0.05),白介素-2(IL-2)、白介素-6(IL-6)、白介素-17(IL-17)、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)水平轻度降低，差异无统计学意义(P>0.05);骨结核患者治疗前后表现为T细胞亚群及相关细胞因子水平初期升高明显，随着骨结核疾病的好转逐渐下降趋于平稳，其中Th1、Th17、Treg、(Th1+Th17)/Treg、IL-2、IL-6、IL-17、IFN-γ、TNF-α的水平变化较为明显，差异有统计学意义(P<0.05)。结论 与非骨结核人群对比，骨结核患者存在以T细胞亚群及细胞因子整体水平降低的免疫机能低下，在抗结核治疗的过程中免疫缺陷逐渐纠正，Th1、Th17、Treg及细胞因子IL-2、IL-6、IL-17、IFN-γ、TNF-α作为骨结核特异性免疫因子发挥着积极的作用。

摘要： Il nuovo fenotipo del paziente diabetico di tipo 1 è caratterizzato dalla presenza di diabete insulino dipendente in concomitanza a sovrappeso o obesità. Recentemente, si è assistito a un incremento significativo di casi correlati alla sedentarietà, a diete ipercaloriche e all’utilizzo di pompe a insulina (CSII) oltre che per il corretto controllo della glicemia, anche per tamponare gli sbalzi glicemici conseguenti a un’alimentazione scorretta. L’incremento di peso che ne consegue, legato all’azione anabolica dell’ormone, aumenta anche il rischio di complicazioni microvascolari e macrovascolari. Sono stati descritti, in soggetti predisposti, disturbi specifici dell’alimentazione legati all’utilizzo dei CSII per il controllo del peso corporeo, fenomeno sempre più frequente soprattutto tra i giovani diabetici. La forma fisica, da sempre, gioca un ruolo cruciale nell’integrazione sociale e nell’accettazione del sé, condizione che rafforza il ricorso all’autogestione del numero di infusioni di insulina per compensare gli effetti di un’alimentazione scorretta. La necessità di un approccio multidisciplinare è indispensabile: l’adozione di stili di vita sani e un utilizzo corretto delle nuove tecnologie per la gestione della malattia diabetica possono essere utili nella gestione del fenomeno.

关键词： Thlaspi arvense (TA)   ulcerative colitis (UC)   TNF-alpha   inflammatory pathway   NF-kappa B   gut microbiota  

摘要： Introduction Thlaspi arvense (TA), commonly known as "Ximi" or "Subaijiang," is a traditional Chinese medicinal herb used to prevent and treat ulcerative colitis (UC). However, the precise mechanisms underlying its therapeutic effects remain unclear, necessitating further investigation to identify potential pharmaceutical applications for UC management. This study aims to elucidate the efficacy and mechanisms of TA and its active constituents in UC *** This study first evaluated the effects of varying TA doses on 3% dextran sulfate sodium (DSS)-induced UC. Gut microbiota alterations in UC mice were analyzed via 16S rRNA sequencing, with correlation analyses to reveal the relationship between gut microbiota and cytokines. Then, network pharmacology was utilized to identified potential TA targets for UC treatment. Protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were employed to explore TA's mechanisms. Molecular docking and dynamics simulations validated interactions between TA's active compounds and UC-related targets. Finally, TNF pathway modulation by TA and its active component, isovitexin, was verified in vitro and in *** TA alleviated DSS-induced weight loss in a dose-dependent manner, reduced disease activity indices, and preserved intestinal mucosal barrier integrity. Subsequently, fluorescence in situ hybridization (FISH) revealed TA suppressed microbial translocation in intestinal tissues. To further characterize inflammatory responses, ELISA demonstrated that TA modulated levels of key cytokines (TNF-alpha, IL-1 beta, IL-6, IL-10) and oxidative stress markers (SOD, MDA), indicating systemic anti-inflammatory effects. Building on these findings, 16S rRNA sequencing analyses showed that TA regulated gut microbiota alpha/beta diversity and inhibited infectious disease-related pathways. Notably, correlation heatmaps highlighted a strong association betw

关键词： 类风湿性关节炎   枸橼酸托法替布片   艾拉莫德   疗效   骨代谢   炎症因子  

摘要： 目的：探讨枸橼酸托法替布片联合艾拉莫德治疗类风湿性关节炎（RA）的效果，并分析其对临床症状体征、炎症反应、白细胞介素-21（IL-21）/信号转导和转录活化因子3（STAT3）信号通路的影响。方法：选取2022年1月至2023年9月RA患者110例分为对照组、观察组，各55例。对照组给予艾拉莫德+甲氨蝶呤治疗，观察组给予枸橼酸托法替布片+艾拉莫德+甲氨蝶呤治疗，连续治疗12 w。比较两组治疗效果及治疗前后临床症状改善情况、血清IL-21/STAT3信号通路因子（IL-21、p-STAT3、STAT3）、炎症指标、骨代谢指标。比较两组不良反应。结果：观察组总有效率为94.55%，高于对照组的80.00%（P＜0.05）；观察组治疗后晨僵时间、关节肿胀数、关节压痛数、VAS评分低于对照组（P＜0.05）；观察组治疗后血清IL-21、p-STAT3、STAT3水平分别为（69.50±14.49）pg/mL、（4.58±1.13）ng/mL、（1.04±0.11）ng/mL，低于对照组的（90.27±20.15）pg/mL、（6.03±1.27）ng/mL、（1.18±0.14）ng/mL（P＜0.05）；观察组治疗后ESR、血清RF、CRP、TNF-α水平分别为（18.47±4.11）mm/h、（83.30±14.36）IU/mL、（15.31±3.22）mg/L、（274.35±23.43）pg/mL，低于对照组的（25.68±4.70）mm/h、（102.58±18.79）IU/mL、（19.06±3.64）mg/L、（321.59±28.82）pg/mL（P＜0.05）；观察组治疗后血清骨钙素N端中分子（N-MID）、总Ⅰ型胶原氨基端延长肽（TPINP）水平高于对照组，β-胶原降解产物（β-CTX）水平低于对照组（P＜0.05）；两组不良反应比较无明显差异（P＞0.05）。结论：枸橼酸托法替布片联合艾拉莫德治疗RA患者，可提高临床疗效，改善临床症状，减轻疼痛程度，抑制炎症反应，改善骨代谢，且具有一定安全性，其疗效机制可能与抑制IL-21/STAT3信号通路有关。

关键词： platelet immunomodulation   rheumatoid arthritis   T lymphocyte activation   CD40L   cytokine production  

摘要： Background: Platelets (PLTs) from healthy donors (HD) modulate T lymphocyte responses but PLTs from rheumatoid arthritis (RA) patients contribute to persistent systemic inflammation. This suggests that PLTs from RA patients and HD have different immunomodulatory effects. Methods: Using cell culture, flow cytometry, proteomics, and ELISA, we compared PLTs from HD and RA patients and their effects on T lymphocyte activation and cytokine production. Results: HD PLTs suppressed T lymphocyte proliferation and IFN gamma and TNF production, while RA PLTs exhibited reduced suppressive capacity. In the presence of RA PLTs, IFN gamma levels correlated with T lymphocyte proliferation, greater disease activity, and anti-citrullinated protein antibodies (ACPA). Proteomic analysis revealed that RA PLTs show upregulation of proteins linked to acute-phase response and complement activation. RA PLTs secreted higher levels of soluble CD40L (sCD40L) and PDGF-BB that correlated with enhanced IFN gamma production. Seropositive RA patients had higher levels of sCD40L, and these levels were predictive of disease remission in RA patients treated with anti-IL6R. sCD40L was found to enhance T lymphocyte activation and to contribute to increased pro-inflammatory cytokine production. Conclusions: This study highlights the diminished ability of RA PLTs to suppress T lymphocyte activation and that sCD40L can be a potential biomarker and therapeutic target in RA.

关键词： 阶梯型   抗人胸腺细胞免疫球蛋白   IST治疗   中药   重型再生障碍性贫血  

摘要： 目的应用创新性的阶梯型兔抗人胸腺细胞免疫球蛋白治疗SAA并评价疗效；方法回顾性分析2023年11月—2024年5月中国中医科学院西苑医院血液科病房明确诊断为获得性SAA患者45例。实验组15例患者为减剂量阶梯方案r-ATG治疗，同时予以环孢素联合海曲波帕口服；30例患者因低风险治疗意愿非随机进入到对照组，选择接受环孢素联合TPO-RA类药物治疗方案，两组患者均予以大菟丝子饮加减补肾生血。结果实验组治疗3个月时客观缓解率（ORR）66.67%；6个月时客观缓解率（ORR）80.00%。对比治疗3个月、6个月与治疗前血细胞计数均值变化，白细胞、中性粒细胞、血红蛋白、血小板、网织红细胞均较治疗前升高，其中治疗3个月血红蛋白、血小板、网织红细胞计数对比治疗前有统计学意义（*P<0.05)；治疗6个月白细胞计数、中性粒细胞计数、血红蛋白、血小板、网织红细胞计数对比治疗前均有统计学意义(*P<0.05)。治疗6个月白细胞计数、中性粒细胞计数对比治疗3个月均有统计学意义(*P<0.05)。与对照组相比，治疗6个月后中性粒细胞计数、血红蛋白、血小板高于对照组，差异具有统计学意义(*P<0.05)。结论新的阶梯型ATG方案在SAA治疗既能够确保疗效，促进骨髓造血功能的恢复，同时有助于降低ATG的副作用，给SAA患者带来低风险IST治疗机遇。

关键词： bladder cancer   interferon gamma response   AGO2   immunotherapy   antitumor immunity   tumor immune microenvironment   STAT1   CD8 T cell   micro-RNA  

摘要： Interferon-gamma (IFN-y), a cytokine essential for activating cellular immune responses, plays a crucial role in cancer immunosurveillance and the clinical success of immune checkpoint blockade therapy. In this study, we show that Argonaute 2 (AGO2), a key mediator in small RNA-guided gene regulation, inversely correlates with tumor responsiveness to IFN-y and the efficacy of immunotherapy. Mechanistically, IFN-y upregulates miR1246 expression in tumor cells, enhancing its interaction with AGO2. This miR-1246-AGO2 complex disrupts IFN-y-mediated signal transducer and activator of transcription 1 (STAT1) phosphorylation by stabilizing protein tyrosine phosphatase non-receptor 6 (PTPN6) mRNA, thereby suppressing the expression of downstream C-X-C motif chemokine ligands (CXCLs), IFN-stimulated genes (ISGs), and human leukocyte antigen (HLA) molecules, which collectively contribute to tumor immune evasion. In preclinical cancer models, inhibiting AGO2 with BCI-137 or targeting miR-1246 with its antagomir re-sensitizes tumor cells to IFN-y, leading to the enhanced recruitment, activation, and cytotoxicity of CD8+ T cells and ultimately improving immunotherapy efficacy.

关键词： BCG   trained immunity   LDLR   type I interferon pathway   antiviral infection   PCSK9 inhibitor   cholesterol   NFE2L1   IRAK1   RIG-I  

摘要： Trained immunity refers to memory-like responses of innate immune cells when they re-encounter pathogenic stimuli. Bacillus Calmette-Guerin (BCG) vaccination implies enhanced antiviral immunity, whereas the underlying mechanisms remain unclear. Herein, we have uncovered elevated expression of low-density lipoprotein receptor (LDLR) on BCG-trained macrophages with robust type I interferon (IFNI) production and antiviral effects both in vivo and in vitro. Consequently, cholesterol is accumulated in BCG-trained macrophages, leading to the augmentation of NFE2L1 expression and the formation of NFE2L1/IRAK1/TRIM25 complex where TRIM25 mediates IRAK1 K63 polyubiquitination to exaggerate IFNI responses in an RIG-I-dependent manner. We have also observed LDLR+ macrophages displaying heightened IFNI responses in BCG-treated human macrophages. To antagonize LDLR degradation by PCSK9 inhibitors increases IFNI responses in the macrophages and accelerated viral clearance. Our study thus couples LDLR upregulation to antiviral activity in BCG-trained macrophages, making commercial PCSK9 inhibitors potential antiviral indications in clinic.

关键词： ginsenoside Rh2   interferon gamma   combination treatment   cancer   Rh2+IFN gamma signature genes (RISG)  

摘要： Interferon gamma (IFN gamma) can amplify immune cell-mediated anti-tumor immunity, as well as directly kill cancer cells. Ginsenoside Rh2 (Rh2), a bioactive compound in traditional Chinese medicine, exhibits anti-cancer effects such as inhibiting proliferation and metastasis. Our earlier research found that Rh2 combined with IFN gamma enhanced CXCL10 secretion in cancer cells. Here, we explored whether Rh2 and IFN gamma exerted more potent anti-cancer activity in vitro and in vivo, along with its mechanisms and clinical value. Our data showed that Rh2 in combination with IFN gamma resulted in a remarkably increased cytotoxicity in colorectal cancer cells including HT29, LoVo and T84 cell lines. Consistently, intratumoral injection with Rh2 plus IFN gamma further restricted the HT29 tumor growth in vivo, and importantly, it was demonstrated to be safe for mice. Meanwhile, the combo treatment activated the stimulator of interferon genes (STING) pathway in cancer cells, promoting the transcription of downstream type I interferon. RNA sequencing revealed a dramatically transcriptional alteration in cancer cells with combo treatment and indicated that Rh2 further augmented the activation of interferon signaling pathway, compared with the IFN gamma alone. Inhibition of janus kinase (JAK) by ruxolitinib could significantly rescue the cell death-triggered by the combo treatment. Then, a gene set named Rh2+IFN gamma signature genes (RISG) was defined, which contained top 20 significantly upregulated genes from the combo treatment. Patients who exhibited a favorable response to the immunotherapy had a higher expression of RISG in tumor compared with those who did not respond. And the high expression of RISG was correlated with better clinical outcome in patients with colorectal cancer (CRC) and skin cutaneous melanoma (SKCM). Herein, the combination of Rh2 with IFN gamma served as a promising strategy for cancer treatment, and its-derived RISG gene set also exhibited potentia

关键词： C. difficile   innate immunity   innate lymphoid cells   interleukin-22   colitis   immunology   infection   mucosal repair   intestinal stem cells  

摘要： Clostridioides difficile causes debilitating colitis via secreted toxins that disrupt the intestinal barrier, and toxemia is associated with severe disease. Thus, therapies that fortify the intestinal barrier will reduce the severity of infection. Innate lymphoid cells (ILCs) are critical in the defense against acute C. difficile infection and represent a promising therapeutic target to limit disease. Here, we report that oral administration of the Toll-like receptor (TLR) 7 agonist R848 limits intestinal damage and protects mice from lethal C. difficile infection without impacting pathogen burden or altering the intestinal microbiome. R848 induced interleukin (IL)- 22 secretion by ILCs, leading to STAT3 phosphorylation in the intestinal epithelium and increased stem cell proliferation. Genetic ablation of ILCs, IL-22, or epithelial-specific STAT3 abrogated R848-mediated protection. R848 reduced intestinal permeability following infection and limited systemic toxin dissemination. Combined, these data identify an immunostimulatory molecule that activates IL-22 production in ILCs to enhance host tissue defenses following C. difficile infection.