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关键词： 术藤方   结直肠癌   肿瘤驯化B细胞   IL-10/STAT3/VEGFC信号轴   淋巴管生成   细胞凋亡  

摘要： 目的:探讨术藤方(ZTF)调控肿瘤驯化B细胞(tumor educated B cell,TEB)抑制结直肠癌淋巴管生成及对白细胞介素-10(interleukin-10,IL-10)/信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)/血管内皮生长因子C(vascular endothelial growth factor C,VEGFC)信号轴的影响。方法:采用超高效液相色谱检测ZTF的活性成分。取***和MC38细胞,采用CCK-8法检测ZTF的半数抑制浓度(half maximal inhibitory concentration,IC_(50))。提取小鼠原代B细胞,构建TEB模型,并以ZTF干预。将TEB分为LPS+Anti-CD40 B cell组、TEB^(CT26)cell/TEB^(MC38)cell组、ZTF-L组、ZTF-M组、ZTF-H组,采用流式细胞术检测细胞凋亡率,ELISA法检测细胞上清中IL-10、VEGFC含量,Western blot法检测p-STAT3、VEGFC蛋白表达水平。收集各组细胞上清干预SVEC4-10细胞,分为LPS+Anti-CD40 B cell CM组、TEB^(CT26)cell/TEB^(MC38)cell CM组、ZTF-L CM组、ZTF-M CM组、ZTF-H CM组,采用细胞迁移实验和成管实验检测迁移细胞数、管腔节点数及管腔长度,Western blot法检测LYVE-1、Podoplanin、VEGFR2、VEGFR3蛋白表达水平。结果:术藤方的活性成分包括柠檬酸、儿茶素、香草酸葡萄糖苷等。与TEB^(CT26)cell/TEB^(MC38)cell组比较,LPS+Anti-CD40 B cell、ZTF-M、ZTF-H组细胞凋亡率升高(P<0.01)。与TEB^(CT26)cell/TEB^(MC38)cell组比较,LPS+Anti-CD40 B cell、ZTF-M、ZTF-H组细胞上清中IL-10、VEGFC含量降低(P<0.01)。与TEB^(CT26)cell/TEB^(MC38)cell组比较,LPS+Anti-CD40 B cell、ZTF-M、ZTF-H组细胞p-STAT3/STAT3、VEGFC蛋白表达水平降低(P<0.05)。与TEB^(CT26)cell CM/TEB^(MC38)cell CM组比较,LPS+Anti-CD40 B cell CM、ZTF-L CM、ZTF-M CM、ZTF-H CM组SVEC4-10细胞迁移数目、管腔节点数及管腔长度减少(P<0.05)。与TEB^(CT26)cell CM/TEB^(MC38)cell CM组比较,LPS+Anti-CD40 B cell CM、ZTF-H CM组细胞LYVE-1、Podoplanin、VEGFR2、VEGFR3蛋白表达水平降低(P<0.05)。结论:ZTF可能通过抑制IL-10/STAT3/VEGFC信号轴,调控TEB,从而抑制淋巴管生成。

关键词： 大剂量甲氨蝶呤   急性淋巴细胞白血病   排泄延迟   预测模型  

摘要： 目的:分析成人急性淋巴细胞白血病(ALL)患者在大剂量甲氨蝶呤(HD-MTX)化疗期间药物排泄延迟的危险因素,并构建风险预测模型,提高临床用药安全。方法:回顾性分析本院在2010年3月至2023年3月收治的39例成人ALL患者,共计完成74例次HD-MTX化疗,应用高效液相色谱法检测MTX用药结束后0、20和44 h血药浓度。依据44 h血药浓度将患者分为排泄延迟组(≥0.3μmol/L)及非排泄延迟组(<0.3μmol/L),比较两组毒副反应的发生率。收集患者的临床资料及实验室检查结果,筛选出与MTX排泄延迟相关的危险因素,采用Logistic回归分析明确MTX排泄延迟的独立危险因素,基于相关危险因素应用R软件构建列线图预测模型,并评估模型的预测价值。结果:74例次化疗共发生27例次排泄延迟,排泄延迟组的黏膜损害及肾功能损害发生率较非延迟组明显增加(均P<0.05)。MTX用量、血尿酸、MTX峰浓度(即用药结束后0 h血药浓度)是MTX排泄延迟的独立影响因素。根据所筛选的3个独立影响因素构建MTX排泄延迟的列线图预测模型,校准曲线、一致性指数、曲线下面积及决策曲线分析法等结果显示该模型良好,具有较好的一致性及区分度。结论:成人ALL在HD-MTX化疗期间MTX排泄延迟发生率较高,基于筛选出的独立影响因素构建的列线图预测模型可用于评估排泄延迟的发生风险,及时甄别出排泄延迟的高危人群,联合MTX血药浓度检测可以个体化调整解救措施,减少毒副作用的发生,保障化疗安全.

关键词： 髓系抗原表达   急性B淋巴细胞白血病   融合基因   基因突变  

摘要： 目的分析伴髓系抗原表达(My+)急性B淋巴细胞白血病(B-ALL)患者的融合基因表达和基因突变情况,进一步探讨不同融合基因阳性My+B-ALL患者的基因突变特点。方法选取116例初诊B-ALL患者,采用多重荧光逆转录聚合酶链反应(RT-PCR)检测14种淋系白血病相关融合基因的表达情况,采用二代测序法检测35个B-ALL相关基因的突变情况,并分析不同融合基因表达情况My+B-ALL患者的基因突变特点。结果116例B-ALL患者中,My+B-ALL患者63例,My-B-ALL患者53例,分别作为My+B-ALL组和My-B-ALL组。116例B-ALL患者中57例检测到4种不同的融合基因:BCR-ABL1、TCF3-PBX1、TEL-AML1、MLL-相关融合基因。My+B-ALL组患者的BCR-ABL1阳性率高于My-B-ALL组,TCF3-PBX1、MLL-相关融合基因只在My-B-ALL组中检出,差异均有统计学意义(P<0.05)。116例B-ALL患者中74例患者计共发生18个基因突变,63例My+B-ALL组患者中39例共计发生15个基因突变,融合基因阳性患者的基因突变率为25.8%,低于融合基因阴性患者的96.9%,差异有统计学意义(P<0.05)。大鼠肉瘤癌基因(RAS)通路相关基因突变均发生在BCR-ABL1阴性患者中。结论My+B-ALL与My-B-ALL的遗传学与分子学存在明显差异,这种差异有助于对My+B-ALL患者发病机制和预后的理解,为精准治疗提供更多的理论基础。

关键词： 神经根型颈椎病   参附舒络丸   艾瑞昔布   LTD4   TNF-α   IL-6   IL-1β  

摘要： 目的:观察参附舒络丸联合艾瑞昔布片治疗神经根型颈椎病(cervical spondylotic radiculopathy, CSR)患者的临床疗效及其对血清细胞因子的影响。方法:选取2021年1月—2024年1月本院收治的82例CSR患者为研究对象进行前瞻性分析,采用随机数字表法将患者分为对照组、观察组,各41例。对照组给予艾瑞昔布片治疗,观察组给予参附舒络丸、艾瑞昔布片联合治疗,疗程4周,比较两组患者的临床疗效;治疗前后进行中医证候积分、颈椎功能障碍指数(NDI)、视觉疼痛模拟评分(VAS)、颈椎活动度评估,酶联免疫吸附法检测血清白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞三烯D4(LTD4)水平,统计不良反应发生率。结果:观察组临床总有效率高于对照组(92.68%VS 75.61%)(P<0.05);治疗4周后,观察组中医证候积分、疼痛VAS评分、NDI评分均低于治疗前和同期对照组(P<0.05);颈椎左旋转、右旋转、左侧屈、右侧屈活动度均大于治疗前和同期对照组(P<0.05);血清LTD4、TNF-α、IL-6、IL-1β水平均低于治疗前和同期对照组(P<0.05);观察组、对照组不良反应总发生率分别为12.20%、4.88%,组间比较无明显差异(P>0.05)。结论:参附舒络丸联合艾瑞昔布片治疗可有效改善CSR患者的临床症状,改善颈椎功能障碍,提高颈椎活动度,抑制炎症反应,增强疗效,且有一定安全性。

关键词： diabetes mellitus   insulin resistance   interleukin-1 beta   interleukin-10   interleukin-6   type 2 diabetes mellitus  

摘要： Background & Objective: This study aimed to elucidate the complex interplay between insulin resistance (IR), type 2 diabetes mellitus (T2DM), and the expression of key inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-1 beta (IL-1β). Methods: A cross-sectional study was conducted involving 100 participants categorized into four groups: IR only (n=30), T2DM without IR (DM-IR, n=20), T2DM with IR (DM+IR, n=20), and healthy controls (HC, n=30). mRNA levels of the cytokines in peripheral blood mononuclear cells (PBMCs) were quantified using qRT-PCR, and serum protein levels were assessed via ELISA. Results: Significant upregulation of IL-6 mRNA in PBMCs was observed in the DM+IR and DM-IR groups compared to controls and the IR only group, while serum IL-6 protein was paradoxically lower in DM+IR compared to DM-IR. Both IL-10 mRNA and serum protein levels were elevated in the DM-IR group, suggesting a compensatory anti-inflammatory response, but were downregulated in the DM+IR group. IL-1β showed a similar pattern, with increased mRNA and serum protein in DM-IR and decreased serum protein in DM+IR. Conclusion: The findings reveal distinct inflammatory cytokine profiles associated with IR and T2DM, highlighting discrepancies between mRNA and protein levels that suggest complex post-transcriptional and translational regulation. These results emphasize the necessity for careful interpretation of cytokine expression in the context of metabolic disorders. © 2025.

关键词： 2型糖尿病   非酒精性脂肪性肝病   脂联素   肿瘤坏死因子   胰岛素样生长因子-1  

摘要： 目的研究2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者血清脂联素(ADPN)、肿瘤坏死因子(TNF-α)、胰岛素样生长因子-1(IGF-1)水平及意义。方法纳入2020年3月至2023年2月本院收治的99例T2DM患者为研究对象,依据是否合并NAFLD分为观察组42例(合并NAFLD)和对照组57例(未合并NAFLD)。比较两组一般资料和血清ADPN、TNF-α、IGF-1水平,分析影响因素,探讨血清ADPN、TNF-α及IGF-1对T2DM合并NAFLD的诊断价值。结果两组性别、身体质量指数(BMI)、收缩压、舒张压、吸烟史、糖尿病家族史、空腹血糖(FPG)及餐后2 h血糖(2 h PG)比较差异均无统计学意义(均P>0.05)。观察组三酰甘油(TG)、胆固醇(TC)、低密度脂蛋白(LDL-C)、空腹胰岛素(FIns)、碱性磷酸酶(ALP)、尿酸(UA)水平均高于对照组,年龄、高密度脂蛋白(HDL-C)水平均低于对照组,上述差异均有统计学意义(均P<0.05)。观察组血清TNF-α水平高于对照组,ADPN、IGF-1水平低于对照组,上述差异均有统计学意义(均P<0.05)。多因素logistic回归分析显示,年龄、HDL-C、FIns、ALP、UA、ADPN、TNF-α及IGF-1是T2DM合并NAFLD的影响因素(均P<0.05)。经受试者工作特征(ROC)曲线分析显示,ADPN、TNF-α及IGF-1诊断T2DM合并NAFLD的AUC值分别为0.643、0.812、0.614(均P<0.05),上述指标联合检测的诊断价值最高(AUC=0.864)。结论T2DM合并NAFLD患者血清TNF-α高表达而ADPN、IGF-1低表达,血清TNF-α、ADPN、IGF-1诊断T2DM合并NAFLD的价值较高。

关键词： 光动力疗法   口腔正畸   牙周炎   炎症反应   牙周菌群  

摘要： 目的探讨光动力疗法协同口腔正畸治疗对牙周炎的应用价值。方法方法选取2021年11月-2024年10月收治的牙周炎患者66例,按随机数表分配法分为研究组和对照组各33例。对照组采用牙周基础治疗联合正畸治疗,研究组在对照组基础上整合光动力疗法进行辅助干预。对比两组疗效、牙周相关指标、炎症反应、牙周菌群情况。结果结果研究组治疗总有效率高于对照组(P<0.05);研究组牙周袋探诊深度(Probing Depth,PD)、附着丧失(Attachment Loss,AL)、牙龈出血指数(Bleeding Index,BI)、菌斑指数(Plaque Index,PLI)均低于对照组(P<0.05);研究组单核细胞趋化蛋白-1(Monocyte Chemoattractant Protein-1,MCP-1)、肿瘤坏死因子-α(Tumor Necrosis Factor-alpha,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-8(Interleukin-8,IL-8)均低于对照组(P<0.05);研究组牙龈卟啉单胞菌、具核梭杆菌、中间拟杆菌数量均低于对照组(P<0.05)。结论结论在治疗牙周炎的过程中,光动力疗法辅助口腔正畸治疗有利于提高临床疗效,减轻炎症反应,改善牙周菌群,值得应用。

关键词： Plasma proteome   Mendelian randomization   Ankylosing spondylitis   Potential drug targets   Causal inference  

摘要： Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the spine and pelvis, leading to ankylosis, stiffness, and reduced quality of life. Despite therapeutic advances, identifying novel drug targets remains critical. Methods: This Mendelian randomization (MR) study leveraged proteome-wide analysis, utilizing data from five genome-wide association studies (GWAS) for proteomics exposure. Outcome data included 3162 European ancestry cases and 294,770 controls from FinnGen R10, and replication analyses used two plasma proteomic datasets (ARIC: 4657 proteins in 7213 individuals;UK Biobank: 4907 proteins in 35,559 participants) and UK Biobank AS GWAS (1344 cases, 324,074 controls). Sensitivity analyses, including Bayesian co-localization and Steiger's direction test, were conducted to ensure robust findings. Protein-protein interaction (PPI) networks were constructed to explore interactions between identified proteins and known AS drug targets. Results: After FDR adjustment, circulating ERAP1 (OR = 1.30, 95 % CI: 1.21-1.39, P = 8.18 x 10(-14)) and IL23R (OR = 2.21, 95 % CI: 1.61-3.03, P = 9.47 x 10(-7)) were genetically linked to increased AS risk, while IL1RL2 showed a protective effect (OR = 0.70, 95 % CI: 0.58-0.85, P = 3.22 x 10(-4)). Steiger's test confirmed directionality (P < 1.70 x 10(-15)), and Bayesian co-localization supported shared causal variants (PPH4 > 0.75 for IL23R/IL1RL2). PPI networks revealed interactions between ERAP1, IL23R, and known AS targets. Replication validated ERAP1 and IL23R associations but not IL1RL2. Conclusion: Genetically determined levels of ERAP1 and IL23R are robustly associated with AS risk, highlighting their potential as therapeutic targets. This study demonstrates the utility of MR in identifying drug targets for complex diseases, providing a foundation for further clinical investigation into their therapeutic potential.

关键词： lymph node   regulatory T cells   peripheral tolerance   rheumatoid arthritis   HLA-DR   fibroblasts  

摘要： Introduction Murine studies have demonstrated that lymph node fibroblasts can present self-antigens via major histocompatibility complex class II molecules, inducing functional regulatory T cells and contributing to peripheral *** To investigate this phenomenon in humans, we developed an in vitro system co-culturing human lymph node fibroblasts with autologous CD4+ T *** Our results reveal that lymph node fibroblasts upregulate human leukocyte antigen-DR (HLA-DR) upon contact with CD4+ T cells and maintain FoxP3 + regulatory T cells. This maintenance is lost upon blockade of HLA-DR or interleukin-2, and regulatory T cells are lost in the absence of lymph node fibroblasts. Furthermore, we demonstrate that lymph node fibroblasts directly isolated from rheumatoid arthritis patients exhibit a significant reduction in the frequency of HLA-DR + cells compared to those from individuals at risk of developing the *** These findings highlight a crucial role for HLA-DR-expressing lymph node fibroblasts in maintaining peripheral tolerance within lymph nodes, a function that may be impaired in autoimmunity. Our study provides novel insights into the intricate cellular interactions within human lymph nodes and their potential implications in autoimmune disorders, opening new avenues for understanding and potentially treating these conditions. This study demonstrates that human lymph node fibroblasts play a crucial role in maintaining regulatory T cell survival via HLA-DR expression. Analysis of lymph node biopsies from rheumatoid arthritis patients revealed a significantly reduced frequency of HLA-DR+ fibroblasts. This finding suggests that defects in these specialized fibroblasts may contribute to the breakdown of immune tolerance and the development of autoimmunity

关键词： 乳腺癌   乳腺癌保乳术   放射治疗   大分割调强放疗   T淋巴细胞  

摘要： 目的 分析早期乳腺癌保乳术中采用常规放疗、大分割放疗的临床价值。方法 选取2021年8月至2022年8月接收的早期乳腺癌患者120例,均行早期乳腺癌保乳手术治疗,按照随机数表形式分为对照组和观察组,每组60例,对照组术后采用常规放疗,观察组采用大分割放疗。对比2组放疗前、后的T淋巴细胞亚群指标(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、肿瘤标志物水平(癌胚抗原、糖类抗原15-3、甲胎蛋白)、不良反应发生情况以及危及器官所受剂量。结果 放疗前,2组T淋巴细胞亚群指标以及肿瘤标志物水平差异均无统计学意义(P>0.05),放疗后,较之于对照组,观察组的CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平更高,CD8^(+)水平更低(P<0.05),且观察组的癌胚抗原、糖类抗原15-3、甲胎蛋白水平均更低(P<0.05);2组总不良反应发生率比较,观察组(6.67%)比对照组(20.00%)更低(P<0.05);观察组危及器官所受剂量均较对照组更低(P<0.05)。结论 在早期乳腺癌保乳术后采用大分割放疗的方式具有积极价值,可有效改善患者的免疫功能,预防或降低不良反应,并可有效减少危机器官放疗剂量,与常规放疗相比,其更加安全有效。