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关键词： Alanine aminotransferase   Entecavir   Finite   Flare   Functional cure   Hepatitis B surface antigen   Hepatitis B virus   Liver cirrhosis   Nucleos(t)ide analogue  

关键词： Arthritis   Lyp   NADPH-Oxidase   Neutrophils   PTPN22  

摘要： Neutrophils are essential for host defense against infections, but they also play a key role in acute and chronic inflammation. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes the lymphoid-specific tyrosine phosphatase (Lyp) and a genetic single-nucleotide polymorphism of PTPN22 rs2476601 (R620W) has been associated with several human autoimmune diseases, including rheumatoid arthritis (RA). Here, we investigated the role of Lyp in TNFα-induced priming of neutrophil ROS production and in the development of arthritis using new selective Lyp inhibitors. Results show that Lyp-selective inhibitors (IC-11 and compound 8b), inhibited TNFα-induced priming of neutrophil superoxide anion production. TNFα induced an increase of Lyp protein expression in human neutrophils isolated from healthy donors. Key pathways involved in neutrophil priming were investigated. Lyp-selective inhibitors, inhibited TNFα-induced p47phox phosphorylation on Ser345, ERK1/2 phosphorylation and Pin1 activation. Interestingly, Lyp expression was increased in neutrophils isolated from synovial fluid of RA patients and Lyp inhibitors, I-C11 and compound 8b prevented superoxide anion production by endogenously primed neutrophils isolated from synovial fluid of RA. Moreover, IC-11 significantly prevented collagen antibody-induced arthritis in mice. These results show that Lyp expression is increased in inflammatory neutrophils, Lyp is involved in TNFα-induced excessive ROS production by neutrophils and its inhibition protected mice against arthritis. Inhibition of Lyp could be a therapeutic strategy in inflammatory arthritis.

关键词： 膝骨关节炎   独活寄生汤   铁死亡  

摘要： 膝骨关节炎（KOA）是一种发病率高且机制复杂的退行性关节疾病，病理表现为关节软骨损伤、滑膜炎症、骨赘增生等，是中老年人群的常见病。铁死亡（ferroptosis）是一种新发现的非凋亡形式的调节性细胞死亡。近年来，中药及复方通过调控铁死亡治疗疾病成为新的热点。本文就膝骨关节炎中铁死亡的发生机制及独活寄生汤可通过调控铁死亡治疗该类疾病展开系统性综述，发现在膝骨关节炎防治过程中，铁死亡显示出巨大的潜力，可能成为该疾病治疗的潜在靶点。独活寄生汤作为中医临床治疗膝骨关节炎的常用经典名方，通过调节铁代谢紊乱、氧化应激、脂质过氧化和炎症反应等铁死亡发生机制，影响膝骨关节炎进程。

关键词： 炙甘黄白汤   过敏性鼻炎   脾肺气虚型   症状评分   嗜酸性粒细胞计数   免疫球蛋白   白细胞介素-4  

摘要： 目的 探讨炙甘黄白汤联合常规西药治疗脾肺气虚型过敏性鼻炎(AR)的效果。方法 选取在2020年3月至2022年3月在该院治疗的脾肺气虚型AR患者96例作为研究对象,分为对照组(48例)和中药组(48例)。对照组使用常规西药治疗,中药组在对照组的基础上加用炙甘黄白汤。治疗1个月后,比较两组患者的治疗总有效率;比较治疗前和治疗1个月后两组鼻部症状(鼻塞、鼻痒、流涕、喷嚏)积分、嗜酸性粒细胞(EOS)计数及免疫球蛋白(Ig E)、白细胞介素-4(IL-4)水平;比较两组治疗后1个月、3个月复发情况。结果中药组总有效率为91.67%,明显高于对照组的77.08%(P<0.05)。治疗前,中药组和对照组的鼻塞、鼻痒、流涕、喷嚏症状评分比较,差异均无统计学意义(P>0.05);治疗后,两组鼻塞、鼻痒、流涕、喷嚏症状评分均低于治疗前(P<0.05),且治疗后中药组鼻塞、鼻痒、流涕、喷嚏症状评分低于对照组(P<0.05)。治疗前,两组EOS计数及Ig E、IL-4水平比较,差异均无统计学意义(P>0.05);治疗后,两组EOS计数及Ig E、IL-4水平均较治疗前下降(P<0.05),且治疗后中药组EOS计数及Ig E、IL-4水平均低于对照组(P<0.05)。两组治疗后1个月复发率比较,差异无统计学意义(P>0.05);治疗后3个月,中药组复发率低于对照组(P<0.05)。结论 炙甘黄白汤与常规西药联合治疗脾肺气虚型AR的效果较好,鼻部症状和EOS计数改善明显,复发率降低。

摘要： Periodontitis was reported to be associated with aspiration pneumonia. However, the relationship between periodontitis and aspiration pneumonia remains unclear. This study investigated the virulence factor of Porphyromonas gingivalis, which exacerbates aspiration pneumonia, and the role of IL-35, an inhibitory heterodimeric cytokine of EBI3 and p35, in aspiration pneumonia using Ebi3 knockout (KO) mice. Aspiration pneumonia was induced by the intratracheal injection of Streptococcus pneumoniae and P. gingivalis culture supernatant (mixed infection). We used leupeptin to inhibit gingipain, a virulence factor of P. gingivalis. Four days after infection, lung tissues were collected for analyses. The percentage of interstitium in the group with mixed infection and leupeptin treatment was significantly reduced compared with the non-leupeptin administration group. Additionally, the percentage of interstitium in the field of Ebi3 KO mice was significantly increased compared with wild-type (WT) mice in mixed infection. IL-35 production in WT mice with mixed infection was significantly increased compared with the Control group. IL-17 production in Ebi3 KO mice was significantly increased compared with WT mice with mixed infection. These findings suggest that gingipain exacerbates aspiration pneumonia and that IL-35 may contribute to suppressing the exacerbation of aspiration pneumonia.

关键词： IL-17A   CEBPβ   osteopontin   LYVE-1   tissue-resident macrophage   cancer immunotherapy   tumor microenvironment   tumor-associated macrophage   monocyte-derived macrophage   triple-negative breast cancer   CP: Cancer   CP: Immunology  

摘要： Tumor-associated macrophages (TAMs) are a critical component of the immunosuppressive tumor microenvironment, comprising monocyte-derived macrophages (MDM-TAMs) and tissue-resident macrophages (TRM-TAMs). Here, we discovered that TRM-TAMs mediate the pro-tumor effects of interleukin (IL)-17A and that IL-17A-driven tumor progression requires tumor cell production of osteopontin (OPN). Mechanistically, we identified CEBPb as a transcription factor downstream of IL-17A in tumor cells and LYVE-1 as an OPN receptor on TRM-TAMs. IL-17A stimulates tumor cell production of OPN, and OPN/LYVE-1 signaling activates the JNK/c-Jun pathway, leading to the proliferation of immunosuppressive LYVE-1+ TRM-TAMs. Unlike its effect on LYVE-1+ TRM-TAMs, OPN interacts with a4b1 to promote the chemotaxis of LYVE-1- MDM-TAMs toward tumors. IL-17A neutralization, OPN inactivation in tumor cells, or LYVE-1 deletion in macrophages inhibited TAMs and enhanced anti-tumor immune responses and anti-PDL1 therapy. Thus, the IL-17A/CEBPb/OPN/LYVE-1 axis offers a mechanism suppressing anti-tumor immune responses and, hence, an effective therapeutic target for cancer.

关键词： 益肾通痹汤   督灸   强直性脊柱炎   Th17偏移   炎症   骨代谢   脊柱骨结构损伤  

摘要： 目的：观察益肾通痹汤联合督灸对强直性脊柱炎患者脊柱骨结构损伤、骨代谢失衡、激素水平及血清白细胞介素23(IL-23)、辅助性T细胞17(Th17)的影响。方法：选取符合纳入标准98例强直性脊柱炎患者，依据随机数字表随机分为对照组和观察组，每组各49例。对照组给予常规西医治疗，观察组在对照组治疗基础上给予益肾通痹汤联合督灸治疗，均连续治疗4周。治疗结束后评估两组临床疗效，分别于治疗前后通过改良Stoke强直性脊柱炎脊柱评分（mSASSS）评价脊柱骨结构损伤情况，强直性脊柱炎功能指数（BASFI）评价脊柱功能，同时比较两组患者中医症状评分变化情况，检测血清核因子-κB、软骨寡聚基质蛋白（COMP）、IL-23、前列腺素E2、缓激肽、人可溶性CD14、多巴胺、骨钙素水平、睾酮、Th17水平。结果：观察组总有效率为97.96%(48/49)，对照组总有效率为81.63%(40/49)，两组比较差异有统计学意义（P <0.05）。治疗后，两组患者中医症状评分、mSASSS评分、BASFI评分、核因子-κB、IL-23、人可溶性CD14、Th17细胞含量、COMP、睾酮、前列腺素E2、缓激肽、多巴胺水平均降低（P <0.05），骨钙素水平升高（P <0.05），且观察组上述指标改善情况优于对照组（P <0.01）。结论：益肾通痹汤联合督灸可明显改善强直性脊柱炎患者Th17偏移，减少炎症，调节骨代谢平衡、睾酮水平，减少疼痛介质含量，减轻脊柱骨结构损伤，缓解病情，提升临床疗效及生活质量。

关键词： BV2   Ischemia–reperfusion injury   Mir-21   Neuroinflammation   Oxygen–glucose deprivation and reoxygenation  

摘要： Elevated inflammatory reactions are a significant component in cerebral ischemia-reperfusion injury (CIRI). Activation of α7-Nicotinic Acetylcholine Receptor (α7nAChR) reduces stroke-induced inflammation in rats, but the anti-inflammatory pathway in microglia under CIRI condition remains unclear. This study employed qRT-PCR, protein assays, NanoString analysis, and bioinformatics to examine the effects of PNU282987 treatment (α7nAChR agonist) on BV2 microglial functional differentiation in oxygen-glucose deprivation/reoxygenation (OGDR) condition. OGDR significantly increased the gene expression of pro-inflammatory markers such as TNF-α, IL-6, and IL1β, while α7nAChR agonists reduced these markers. The anti-inflammatory gene marker IL-10 was upregulated by α7nAChR agonist treatment. Downstream pathway marker analysis showed that both gene and protein expression of NFκB was associated with anti-inflammatory effects. Blocking microRNA-21 with antagomir reversed the anti-inflammatory effects. NanoString analysis revealed that microRNA-21 inhibition significantly affected inflammation-related genes, including AL1RAP, TLR9, FLT1, PTGIR, NFκB, TREM2, TNF, SMAD7, FOS, CCL5, IFIT1, CFB, CXCL10, IFI44, DDIT3, IRF7, OASL1, IL1A, IFIT2, C3, CD40, STAT2, IFIT3, IL1RN, OAS1A, CSF1, CCL4, CCL2, CCL3, BCL2L1, and ITGB2. Enrichment analysis of upregulated genes identified Gene Ontology Biological Processes related to cytokine responses and TNF-associated pathways. This study highlights α7nAChR activation as a key regulator of anti-inflammatory responses in BV2 microglia under OGDR conditions, with micro-RNA21 identified as a crucial mediator of receptor-driven neuroprotection via the TNF-α/NFκB signalling pathway.

关键词： 电针   溃疡性结肠炎   白细胞介素-6   信号转导与转录活化因子3   辅助性T细胞   调节性T细胞  

摘要： 目的 观察电针通过调控白细胞介素-6(IL-6)/信号转导与转录活化因子3(STAT3)信号通路，影响葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）小鼠辅助性T细胞17(Th17)/调节性T细胞（Treg）之间的免疫平衡，探讨电针治疗UC的部分机制。方法 雄性C57BL/6N小鼠采用DSS自由饮水法建立UC模型后，随机分为模型组、电针组、和假针组，每组10只，另取10只作为空白对照组。选取双侧“天枢”“上巨虚”进行电针或假针治疗，每次20 min，共10次。观察各组小鼠的一般情况、疾病活动指数（DAI）,HE染色法观察结肠组织病理学变化，ELISA法检测血清中IL-6、IL-10和IL-17含量，Western blot法检测结肠组织中IL-6、STAT3、维甲酸相关孤儿受体（RORγt）和叉头框蛋白P3(FoxP3)的蛋白表达水平，流式细胞术检测小鼠脾脏中Th17和Treg细胞的占比。结果 与空白组相比，模型组小鼠DAI评分明显升高（P<0.01），出现结肠黏膜破损、大量炎性细胞浸润等表现，血清IL-6、IL-17含量明显增加（P<0.01）、IL-10含量明显减少（P<0.01），结肠组织中IL-6、STAT3和RORγt的表达均明显增加（P<0.01）,FoxP3的表达降低（P<0.05），脾脏中Th17细胞百分比升高、Treg细胞百分比降低（P<0.05）。与模型组相比，电针组小鼠DAI评分降低（P<0.05），结肠损伤减轻，炎性浸润减少，血清IL-6、IL-17含量减少、IL-10含量增加（P<0.05），结肠组织中IL-6、STAT3、RORγt表达均明显降低（P<0.01）、FoxP3表达增加（P<0.05），脾脏中Th17细胞百分比下降、Treg细胞百分比升高（P<0.05）。而假针组小鼠结肠损伤未见好转，与模型组相比，各指标变化未见统计学差异。结论 电针可能通过下调IL-6/STAT3信号通路，促进Th17/Treg恢复免疫平衡，从而改善UC小鼠的肠道炎症，发挥治疗UC的作用效应。