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关键词： 白细胞介素31   巨噬细胞极化   类风湿性关节炎   线粒体DNA  

摘要： 目的探讨白细胞介素(interleukin,IL)-31激活PI3K/AKT2/HIF-1α通路导致巨噬细胞M1型极化的机制,为类风湿性关节炎(rheumatoid arthritis,RA)发病机制的阐明提供新思路。方法选用人单核细胞白血病细胞系(THP-1),根据处理方法进行分组。实时荧光定量PCR(quantitative reverse transcription PCR,RT-qPCR)和免疫印迹法(Western blot,WB)检测空白对照组和IL-31刺激组巨噬细胞中线粒体相关基因线粒体外膜转位酶20(mitochondrial permeability porin 20,TOMM20)、电压依赖性阴离子通道1(voltage-dependent anion channel 1,VDAC1)、线粒体转录因子A(mitochondrial transcription factors A,TFAM)的表达。RT-qPCR检测空白对照组和IL-31刺激组巨噬细胞胞质和培养液中线粒体DNA(mitochondrial DNA,mtDNA)拷贝数变化。RT-qPCR、WB和化学发光法检测IL-31以及溴化乙锭(ethidium bromide,Etbr)处理后巨噬细胞中PI3K/AKT2/HIF-1α通路的激活情况。在IL-31和Etbr的基础上敲低磷脂酰肌醇3激酶(phosphatidylinositol 3 kinase,PI3K),检测肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和IL-1β的表达。结果IL-31处理后巨噬细胞中的TOMM20、VDAC1和TFAM的mRNA和蛋白表达均明显降低(t=5.11、14.43、8.82、3.80、56.27、4.67,P值均<0.05),线粒体发生损伤功能障碍,胞质中和细胞外的mtDNA拷贝数增加(t=5.01、12.00,P值均<0.05)。释放到巨噬细胞胞质中的mtDNA激活了PI3K/AKT2/HIF-1α通路。使用Etbr刺激巨噬细胞后敲低PI3K,细胞中的TNF-α和IL-1β的mRNA和蛋白表达均明显降低(t=11.61、5.16、12.09、2.74,P值均<0.05)。结论IL-31诱导巨噬细胞M1型极化的机制为IL-31通过促进mtDNA向胞质中释放,激活PI3K/AKT2/HIF-1α轴,引起炎症因子TNF-α和IL-1β分泌。

关键词： 胎盘植入性疾病   TRAIL-R2   IL-35   ROC   预测价值  

摘要： 目的探究血清肿瘤坏死因子相关凋亡诱导配体受体2(TRAIL-R2)和白细胞介素-35(IL-35)在胎盘植入性疾病(PAS)中的表达和临床意义。方法回顾性选取2021年4月至2024年4月长沙市妇幼保健院诊治的PAS患者为观察组,另选同期健康孕妇为对照组。收集研究对象临床资料并测定血清TRAIL-R2和IL-35水平。采用相关性分析探讨血清TRAIL-R2、IL-35水平与PAS的相关性。行多因素Logistic回归分析筛选PAS发生的独立危险因素,受试者操作特征(ROC)曲线及其曲线下面积(AUC)评估血清TRAIL-R2、IL-35水平单独及联合检测对PAS的诊断效能。结果共纳入160例研究对象,观察组100例,包括胎盘植入组63人、胎盘粘连组37人,对照组60例。观察组血清TRAIL-R2水平显著低于对照组、IL-35水平显著高于对照组(P<0.001);观察组中,胎盘植入组TRAIL-R2水平显著低于胎盘粘连组,但IL-35水平显著高于胎盘粘连组(P<0.001)。相关性分析显示,血清TRAIL-R2(Eta系数=0.513)、IL-35(Eta系数=0.485)水平均与PAS有较高相关性。Logistic回归分析结果显示,孕次>2次、剖宫产史、胎盘评分越高、血清TRAIL-R2水平降低和IL-35水平升高为PAS发生的独立危险因素(P<0.01)。ROC分析显示,TRAIL-R2联合IL-35诊断PAS的AUC为0.887、灵敏度为0.950、特异度为0.710,二者联合诊断效能显著优于单一诊断(P<0.05)。结论血清TRAIL-R2水平异常降低及IL-35水平异常升高是PAS发生的独立危险因素,且二者联合检测对PAS具有较高的早期诊断价值。

关键词： Guselkumab   Inflammatory Bowel Diseases   Mirikizumab   Risankizumab   anti-IL23p19  

摘要： A wide range of advanced therapies has become available in recent years for the treatment of moderate-to-severe inflammatory bowel disease (IBD). Among these, monoclonal antibodies targeting the interleukin 23 p19 subunit (anti-IL23p19) have emerged as a promising therapeutic class. Pivotal Phase 3 trials have demonstrated their favourable clinical efficacy and safety in both Crohn's disease (CD) and ulcerative colitis (UC). Three such agents, Risankizumab, Mirikizumab and Guselkumab, have now been approved in CD and UC. For gastroenterologists, the ability to rationally select among these options to personalise treatment and maximise patient benefit is critical. Key factors to consider when selecting an anti-IL23p19 agent include patient preference regarding mode of administration, IBD phenotype, presence of co-existing extra-intestinal manifestations, concomitant immune mediated diseases and previous advanced-therapy exposure. Our review summarises the current clinical evidence on anti-IL23p19 therapies and provides practical guidance on their use in IBD clinical management, including dosing strategies, choice of dose in CD and UC and clinical positioning across patients. Finally, anti-IL23p19 inhibition may represent a future first-line therapy option for moderate-to-severe IBD, particularly in patients with concomitant IL-23 driven co-morbidities such as psoriasis. Its use in combination with other advanced therapies in selected patients is being explored to enhance therapeutic efficacy and improve long-term outcomes. Further real-world studies are needed to assess its effectiveness and benefits in complex disease phenotypes, including perianal fistulizing Crohn's disease.

关键词： 地衣芽孢杆菌   诺如病毒性肠炎   炎症因子   肠道菌群  

摘要： 目的分析地衣芽孢杆菌治疗诺如病毒性肠炎患儿的临床效果及对血清PCT、IL-6水平的影响。方法采用随机数字表法将2022年4月-2023年4月我院诊治的74例诺如病毒性肠炎患儿分为对照组和观察组,各组37例。对照组采用对症综合治疗,观察组在对照组基础上给予地衣芽孢杆菌活菌胶囊治疗,对两组治疗效果、炎症因子水平[降钙素原(PCT)、白细胞介素-6(IL-6)]、临床症状消失时间、肠道菌群水平、不良反应发生率进行比较。结果观察组治疗总有效率(94.59%)高于对照组(83.78%)(P<0.05);两组治疗后血清PCT、IL-6水平较治疗前低,且相较于对照组,观察组治疗后血清PCT、IL-6水平更低(P<0.05);观察组发热、呕吐、腹泻消失时间较对照组短(P<0.05);两组治疗后乳酸菌、双歧杆菌数量较治疗前高,且相较于对照组,观察组治疗后乳酸菌、双歧杆菌数量更高(P<0.05);观察组不良反应发生率与对照组相比,差异无统计学意义(P>0.05)。结论地衣芽孢杆菌治疗可提升诺如病毒性肠炎患儿治疗总有效率,在较短时间内减轻临床症状,改善乳酸菌和双歧杆菌水平,抑制炎症反应,且应用安全性较高。

关键词： Kinsenoside   Pain   Anti-inflammation   ER stress   Glutamatergic transmission  

摘要： Neuro-inflammation contributes to neuropathic pain by sensitizing ionic channels. Kinsenoside, a traditional Chinese medicine, has recognized anti-inflammatory properties. However, it remains unclear whether kinsenoside can be used for pain therapy. Network pharmacology analysis revealed that 57 % of its targets are associated with pain, including inflammation and synaptic transmission. The analgesic effects of kinsenoside were confirmed in SNL and formalin rat models, with ED50 values of 47.99 mu g and 36.80 mu g, respectively. Transcriptome and WGCNA analyses indicated the involvement of cytokine release, anti-inflammatory activity, and synapse enrichment in the blue module. Furthermore, we confirmed that kinsenoside's efficacy was mainly mediated by IL-10 induction, phosphorylation of STAT3, and SOCS3 expression. Pretreatment with kinsenoside significantly inhibited the release of TNF-alpha, IL-1 beta, and IL-6. Kinsenoside also attenuated ER stress in both microglia and neural cells. Molecular docking analysis demonstrated significantly high binding energies of IL-10, STAT3, and SOCS3 with MHC. Additionally, whole-cell recordings revealed that bath application of kinsenoside reduced the frequency and amplitude of spinal glutamatergic transmission in a dose-dependent manner. In summary, pharmacological prediction and biological validation collectively indicate that kinsenoside significantly exerts significant analgesic effects by attenuating ER stress and inhibiting inflammatory responses via the IL-10/p-STAT3/SOCS3 axis, precisely regulating spinal glutamatergic transmission for pain relief.

关键词： 骨髓瘤细胞   单克隆抗体   多发性骨髓瘤   致病机理   症状与治疗  

摘要： 介绍骨髓瘤细胞的定义,单克隆抗体制备中如何获取骨髓瘤细胞,选用同源品系骨髓瘤细胞的原因,多发性骨髓瘤的病因、症状提示及治疗方案,通过问题释疑强化学生对生物学专业名词的新认识,树立稳态与平衡观。

关键词： 口腔鳞状细胞癌   肝细胞生长因子   间充质上皮转化因子   作用机制   磷脂酰肌醇3-激酶   蛋白激酶B   表皮生长因子   靶向治疗   单克隆抗体   酪氨酸激酶抑制剂  

摘要： 口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)是严重威胁人类健康的恶性肿瘤,其典型的生物学特征包括局部侵袭性强、淋巴结转移率高以及治疗后易复发等特点。来源于间充质的肝细胞生长因子(hepatocyte growth factor,HGF)、间充质上皮转化因子(cellular-mesenchymal to epithelial transition factor,c-Met)及HGF/c-Met信号通路参与调控OSCC的发生发展。一方面,HGF和c-Met蛋白在OSCC中过表达,且多项研究提示与肿瘤恶性特征和不良预后显著相关;HGF/c-Met信号通路的异常激活(由HGF依赖性自/旁分泌或MET基因突变、扩增、融合及蛋白过表达等非依赖性机制驱动)可通过激活下游信号通路,协同促进肿瘤细胞侵袭转移和血管生成;另一方面,HGF/c-Met还可通过促进乳酸分泌增加、诱导程序性细胞死亡配体(programmed death ligand 1,PD-L1)表达上调、激活和扩增髓源性抑制细胞以及促进调节性T细胞(regulatory T cells,Tregs)细胞增殖的方式介导免疫逃逸;此外,HGF/c-Met信号通路与磷脂酰肌醇3-激酶(phosphatidylinositide 3-kinases,PI3K)/蛋白激酶B(protein kinases B,AKT)、表皮生长因子(epidermal growth factor receptor,EGFR)、Janus激酶(Janus kinase,JAK)/转录激活蛋白(signal transducer and activator of transcription,STAT3)等关键通路和非编码RNA形成的串扰也可促进肿瘤进展。针对这一通路,目前已开发出三类靶向药物:HGF单抗、c-Met单抗和酪氨酸激酶抑制剂,其中部分药物已进入临床试验阶段。然而,治疗过程中出现的耐药现象,特别是EGFR等替代信号通路的双向代偿性激活,成为临床面临的重大挑战。本文通过深入分析HGF/c-Met通路在OSCC中的作用机制及其与其他通路的交互关系,梳理现有治疗药物的研究现状,旨在为开发更有效的联合治疗策略、实现个体化精准治疗提供重要依据,最终改善患者的临床预后和生活质量。

关键词： lactic acid bacteria   ulcerative colitis   gut microbiota   inflammatory cytokines   intestinal barrier  

摘要： Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracasei L21 (L. paracasei L21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracasei L21 decreased levels of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracasei L21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-kappa B signaling while activating HIF1 alpha/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracasei L21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracasei L21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies.

关键词： 心功能不全   心房颤动   可溶性白细胞分化抗原14   组蛋白去乙酰化酶3   白细胞介素-6  

摘要： 目的探讨心功能不全并发心房颤动(简称房颤)患者血清可溶性白细胞分化抗原14(sCD14)、组蛋白去乙酰化酶3(HDAC3)、白细胞介素-6(IL-6)水平及其意义。方法选取2023年2月至2024年3月于该院住院的心功能不全患者254例为研究对象,根据是否并发房颤分为房颤组(96例)和非房颤组(158例),所有房颤患者均确诊为房颤且均为持续性房颤。收集所有患者资料,检测所有患者血清sCD14、HDAC3、IL-6水平,采用多因素Logistic回归分析心功能不全患者并发房颤的影响因素,分析心功能不全并发房颤患者血清sCD14、HDAC3、IL-6水平与心功能分级、N末端B型钠尿肽前体(NT-proBNP)水平的相关性,绘制受试者工作特征(ROC)曲线分析血清sCD14、HDAC3、IL-6单项及3项联合对心功能不全患者并发房颤的诊断价值。结果2组患者心功能分级及NT-proBNP、HDAC3、IL-6、sCD14水平比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,心功能分级为Ⅲ级或Ⅳ级及NT-proBNP、sCD14、HDAC3、IL-6水平升高均是心功能不全患者并发房颤的危险因素(P<0.05)。心功能不全并发房颤患者的血清sCD14、HDAC3、IL-6水平与心功能分级、NT-proBNP水平均呈正相关(P<0.05)。ROC曲线分析结果显示,血清sCD14、HDAC3、IL-6诊断心功能不全患者并发房颤的曲线下面积(AUC)分别为0.860、0.855、0.771,3项联合诊断的AUC为0.955,3项联合诊断的AUC高于sCD14(Z=2.952,P=0.011)、HDAC3(Z=3.205,P=0.009)、IL-6(Z=5.129,P<0.001)单项诊断的AUC。结论血清sCD14、HDAC3、IL-6水平升高是心功能不全患者并发房颤的危险因素且对其具有一定的诊断价值,3项联合诊断价值更高。

关键词： 糖类抗原72-4   糖类抗原19-9   神经元特异性烯醇化酶   食管癌   远处转移  

摘要： 目的探讨血清糖类抗原72-4(CA72-4)、糖类抗原19-9(CA19-9)、神经元特异性烯醇化酶(NSE)水平与食管癌远处转移的关系。方法选取102例食管癌患者作为食管癌组,93例良性食管疾病患者作为良性组,比较两组患者血清CA72-4、CA19-9、NSE水平。采用病理检查确定食管癌患者是否发生远处转移,比较发生远处转移和未发生远处转移食管癌患者血清CA72-4、CA19-9、NSE水平。采用Spearman法分析血清CA72-4、CA19-9、NSE水平与食管癌远处转移的相关性。结果食管癌组患者血清CA72-4、CA19-9、NSE水平均明显高于良性组,差异均有统计学意义(P<0.01)。经病理检查,9例食管癌患者发生远处转移(转移组),93例食管癌患者未发生远处转移(未转移组)。转移组患者血清CA72-4、CA19-9、NSE水平均高于未转移组,差异均有统计学意义(P<0.05)。血清CA72-4、CA19-9、NSE水平与食管癌远处转移均呈正相关(P<0.05)。结论在食管癌患者中,血清CA72-4、CA19-9、NSE水平明显升高,且血清CA72-4、CA19-9、NSE水平与食管癌远处转移均呈正相关。