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关键词： IL6ST   LIF signaling   Skeletal dysplasia   Autosomal recessive  

摘要： Stüve-Wiedemann syndrome is a rare skeletal dysplasia characterized by severe shortening and bowing of the long bones and by immunological and autonomous dysfunction, usually resulting in early death. Bi-allelic loss-of-function variants in either the leukemia inhibitory factor receptor encoding LIFR or the interleukin-6 cytokine family signal transducer encoding IL6ST are causative. So far, five individuals from three unrelated families were described with IL6ST associated Stüve-Wiedemann syndrome. We here report on a sixth case that came to attention at 21 weeks of gestation with short and bowed long bones. Prenatal trio exome sequencing revealed the homozygous novel variant p.(Ser375∗) in IL6ST in the fetus. The further course of the pregnancy was complicated by early rupture of the membranes and preeclampsia. The fetus died in utero in gestational week 34 and was born with dolichocephalus, severe bowing and shortening of limb bones, a narrow upper thorax, joint dislocations and abnormal bone mineralization. With this case report, we further delineate the molecular and clinical spectrum of IL6ST related Stüve-Wiedemann syndrome.

关键词： 结核   抗结核药   超敏反应   酶联免疫斑点法   干扰素γ  

摘要： 背景抗结核药物超敏反应在临床上常见,药物激发试验是目前唯一有效的找出致敏药物的方法,但可诱发患者再次出现过敏甚至休克,严重时危及患者生命;也有患者放弃治疗导致结核菌耐药和播散。由于目前常用的抗结核方案需要4种药物联合使用,如何及时、精确地找出诱导患者出现超敏反应的致敏药物是临床迫切需要解决的问题。目的评估干扰素γ(IFN-γ)酶联免疫斑点法在快速识别出诱导抗结核药物治疗患者发生超敏反应的致敏药物中的临床价值。方法选取2021—2022年住院治疗的初治敏感肺结核且在治疗过程中发生药物超敏反应的患者50例,采集患者过敏急性期外周血单个核细胞,用酶联免疫斑点法检测药物特异性IFN-γ释放细胞的情况,采用药物激发试验作为判定何种药物诱导的超敏反应的金标准;分析酶联免疫斑点检测对识别抗结核四联方案(异烟肼、乙胺丁醇、利福平、吡嗪酰胺)所致超敏反应中的临床价值。结果酶联免疫斑点法在识别异烟肼、乙胺丁醇、利福平、吡嗪酰胺所致超敏反应中的灵敏度分别为69.2%(35/50)、61.5%(31/50)、75.0%(38/50)、66.7%(33/50),特异度为97.3%(49/50)、100.0%(50/50)、100.0%(50/50)、100.0%(50/50)。结论IFN-γ酶联免疫斑点检测在抗结核药物超敏反应患者急性期需进行致敏药物识别时,可作为一种体外检测的有效手段。

关键词： HSP90   ADAM33   IL-lβ   支气管哮喘   治疗效果  

摘要： 目的:探讨血清热休克蛋白90(HSP90)、解整合素-金属蛋白酶33(ADAM33)、白细胞介素-1β(IL-1β)水平联合检测对支气管哮喘(简称哮喘)患儿治疗效果的评估价值。方法:选取2022年1月至2024年3月周口市中心医院177例哮喘患儿为研究对象,依据病情程度分为重度组(n=44)、中度组(n=61)、轻度组(n=72),另选取同期177例健康体检儿童为对照组。对比4组入院时血清HSP90、ADAM33、IL-lβ水平并分析其相关性,采用Logistic回归分析影响患儿治疗效果的单因素及多因素,并分析各指标水平联合检测对患儿治疗效果的预测价值。结果:4组入院时血清HSP90、ADAM33、IL-lβ水平比较,对照组<轻度组<中度组<重度组(P<0.05);入院时血清HSP90、ADAM33、IL-lβ水平均与患儿病情程度呈正相关(P<0.05);未有效控制患儿入院时动脉血二氧化碳分压(PaCO_(2))、HSP90、ADAM33、IL-lβ均高于有效控制、动脉血氧分压(PaO_(2))均低于有效控制患儿(P<0.05);PaCO_(2)、HSP90、ADAM33、IL-lβ水平为哮喘患儿未有效控制的危险因素,PaO_(2)为哮喘患儿未有效控制的保护因素(P<0.05);入院时血清HSP90、ADAM33、IL-lβ水平联合预测患儿未有效控制的效能为0.927,均高于各指标单独预测(P<0.05)。结论:哮喘患儿血清HSP90、ADAM33、IL-lβ水平与病情程度有关,其联合检测可有效预测患儿治疗效果,为早期临床合理治疗提供参考。

关键词： Feline calicivirus infection   IL-1β   NF-κB   TLR2  

摘要： Feline calicivirus (FCV) induces systemic inflammation in felines, posing a serious threat to feline health worldwide. Severe cases may lead to chronic stomatitis and other inflammatory conditions. However, the precise mechanisms underlying FCV-induced inflammation remain unclear. To investigate the involvement of toll-like receptors (TLRs), in vitro experiments assessed changes in TLR gene expression following FCV infection. FCV infection significantly upregulated TLR2 and TLR7 transcription, as well as expression of the NLRP3 gene. Functional assays revealed that inhibition or silencing of TLR2 markedly reduced FCV-induced transcription and secretion of proinflammatory cytokines IL-1β, IL-6, and TNF-α. Conversely, TLR2 overexpression enhanced IL-1β transcription and secretion, further implicating TLR2 in FCV-mediated inflammatory signaling. Mechanistically, FCV infection increased the expression of TLR2 and MyD88, promoted IκBα phosphorylation and degradation, and facilitated NF-κB (p65) phosphorylation and nuclear translocation. Disruption of TLR2 or MyD88 abrogated these events, thereby blocking NF-κB activation and downstream IL-1β expression. Inhibition of any component within the TLR2/MyD88/NF-κB axis—including NF-κB or IκBα—similarly suppressed IL-1β transcription, expression, and secretion, establishing the central role of this pathway in FCV-induced inflammation. Further experiments demonstrated that FCV virus-like particles (VLPs) can induce IL-1β gene transcription through the TLR2/MyD88/NF-κB axis but are insufficient to trigger IL-1β secretion. Dual-luciferase assays confirmed that FCV VP1 alone is capable of activating IL-1β gene transcription via this pathway and directly interacts with TLR2. Collectively, these findings demonstrate that FCV VP1 binds to TLR2, initiates IκBα phosphorylation through MyD88, promotes nuclear translocation of NF-κB (p65), and activates the NF-κB signaling cascade. This cascade primes the inflammasome by inducing transcri

关键词： antibodies   antibody-mediated rejection   graft dysfunction   heart transplantation   HLA antigens   immunotherapy   AMR   antibody-mediated rejection   ACR   acute cellular rejection   AR   acute rejection   BNR   biopsy-negative rejection   dd-cfDNA   donor-derived cell-free DNA   dnDSA   de novo donor-specific antibody   DSA   donor-specific antibody   EMB   endomyocardial biopsy   HT   heart transplantation   HLA   human leukocyte antigen   IVIG   intravenous immunoglobulin   pAMR   pathologic antibody-mediated rejection  

摘要： Heart transplantation remains the definitive therapy for patients with advanced heart failure. Acute and chronic rejection affect both short- and long-term outcomes. Antibody-mediated rejection (AMR) remains a leading cause of graft failure and mortality. The reported incidence of AMR varies widely, on the basis of patient characteristics, variability in the interpretation of endomyocardial biopsy, and differences in clinical thresholds at which to treat AMR. There has been increased recognition of the role of human leukocyte antigen donor-specific antibodies and molecular diagnostics, such as donor-derived cell-free DNA or intragraft gene expression, in supporting the diagnosis of AMR beyond histopathology alone. Furthermore, therapeutic management of patients with AMR previously focused on quelling inflammation, removing or neutralizing pathological antibodies, and blocking antibody-producing cells. Novel therapies now also target complement-mediated injury, costimulatory blockade, and specific cytokine-mediated inflammatory pathways. This position statement highlights contemporary diagnostic and therapeutic approaches for AMR after heart transplantation.

关键词： HLA-B*15:02   LAMP-IDE-AI   POCT   Adverse drug reactions  

摘要： The HLA-B*15:02 allele is strongly associated with adverse drug reactions induced by aromatic antiseizure medications such as carbamazepine and oxcarbazepine. Consequently, it is strongly recommended to test for the presence of the HLA-B*15:02 allele before prescribing these medications. Traditional HLA genotyping methods (e.g. polymerase chain reaction or Sanger sequencing) require laboratory environments and expert personnel, resulting in a typical report turnaround time of 1–2 weeks. In this study, we developed a rapid point-of-care test (POCT) using the LAMP-IDE-AI platform for the automatic detection of the HLA-B*15:02 allele within one hour. We evaluated the platform's performance using blood samples collected from 537 children presented with a convulsion, comparing the results obtained with the LAMP-IDE-AI platform to those from PCR tests and further verifying them with Sanger Sequencing. The LAMP-IDE-AI platform exhibited 100 % sensitivity, correctly detecting all 25 positive samples. Meanwhile it demonstrated a specificity of 99.8 %, with only one sample yielding a "False Positive" result. These findings suggest that the LAMP-IDE-AI platform could potentially serve as a rapid, automated, simple, and accurate POCT for detecting the HLA-B*15:02 allele in clinical application.

关键词： 骨细胞   骨衰老   免疫微环境   免疫细胞   细胞因子   免疫衰老   免疫治疗   工程化组织构建  

摘要： 背景:骨骼微环境中富含各种免疫细胞和细胞因子,它们与骨细胞紧密联系形成了相互影响的网络,因此,骨骼的衰老不单单是由骨细胞衰老导致,免疫系统衰老同样会加速骨衰老过程。目的:综述骨髓间充质干细胞、成骨细胞和破骨细胞以及骨微环境中免疫细胞的年龄相关变化,强调免疫微环境在骨衰老中的关键作用以及免疫治疗在骨衰老治疗中的潜力。方法:检索PubMed数据库、中国知网中关于骨骼细胞衰老与免疫细胞衰老相互作用的文献,英文检索词为“Osteocytes,Bone aging,Immune microenvironment,Immune cells,Cytokines,Immunosenescence,Immunotherapy”,中文检索词为“骨细胞,骨衰老,免疫微环境,免疫细胞,细胞因子,免疫衰老,免疫治疗”。根据纳入与排除标准,最终纳入128篇文献进行综述。结果与结论:骨衰老是老年人普遍存在的一种病理状态,以多种生物学过程相互作用为特征,其中免疫因素起着关键作用。免疫微环境中的细胞、分子和信号通路共同构成了一个复杂的网络,这个网络的失衡会加速骨衰老进程。抗细胞衰老与免疫治疗相结合可能为骨衰老疾病的治疗带来新的方法,包括清除衰老的细胞、衰老相关分泌表型靶向药物、炎症细胞因子靶向治疗、免疫细胞调节疗法、干细胞治疗及分子治疗等。为了更有效且合理地清除衰老细胞,需要更深入地了解衰老细胞的机制,这将有助于更准确地识别衰老细胞。免疫治疗在骨衰老治疗中展现出强大的潜力和前途,但存在一些潜在的风险。相信随着科技的进步,人们可以更准确地了解人体的遗传信息和免疫状态,制定更个性化的免疫治疗方案。

关键词： Inflammatory bowel disease   Probiotic therapy   TNF-alpha   Inflammatory cytokines   Oxidative stress  

摘要： Oral probiotic therapy holds great promise for inflammatory bowel disease (IBD) by virtue of its non-invasive nature and ability to modulate inflammation, but its potential remains limited by insufficient probiotic colonization and incomprehensive therapeutic intervention. Herein, we developed a versatile oral-administrated system, termed EcN-Ap@A/H-Ce, designed to combat chronic relapsing IBD by downregulating inflammatory cytokines (e.g., TNF-alpha) and scavenging reactive oxygen species (ROS). By conjugating TNF-alpha aptamers to the surface of Escherichia coli Nissle 1917 (EcN) and encapsulating the engineered probiotic into uniform-sized pH-responsive sodium alginate microspheres via microfluidic technology, a dual-layered microcapsule system was further constructed with an outer composite coating of hyaluronic acid (HA) and CeO2 nanozymes through liquid interface self-assembly. As expected, the system exhibited robust resistance to the harsh gastrointestinal environment. The HA coating enhanced colon-targeting efficiency, while the CeO2 nanozymes alleviated oxidative stress and promoted EcN-Ap colonization. Concurrently, EcN-Ap neutralized TNF-alpha, suppressed inflammation, and restored intestinal barrier integrity. In a murine colitis model, the EcN-Ap@A/H-Ce microcapsule revealed a substantially improved therapy than conventional oral-administrated mesalamine and even achieved comparable therapeutic benefits with clinical intravenous-administrated infliximab while avoiding unpleasant invasive administration. Notably, 16S sequencing revealed enhanced gut microbiota modulation, particularly increasing beneficial Akkermansiaceae populations. This multifunctional microcapsule provides comprehensive IBD treatment with low side effects and improved patient compliance, representing a promising non-invasive alternative for the effective management of IBD and other gastrointestinal disorders.

关键词： GTS   CUMS   抑郁症   细胞因子  

摘要： 目的:本研究通过建立慢性不可预见性温和应激(chronic unpredicted mild stress, CUMS)大鼠抑郁模型,观察人参总皂苷(ginseng total saponins, GTS)对前额叶皮质(prefrontal cortex, PFC)细胞因子表达水平的调控作用,探讨其发挥抗抑郁作用的机制。方法:48只雄性无特定病原体(specific pathogen free, SPF)动物级(sprague-dawley, SD)大鼠适应性喂养1 w后,按照数字随机法分为6组(n=8):正常对照组,模型组,GTS低、中、高剂量组(13 mg/kg, 26 mg/kg, 52 mg/kg)和阳性药物对照组(盐酸帕罗西汀,2.06 mg/kg),每组分两笼饲养。除正常对照组外,给予夹尾、禁食、禁水、鼠笼倾斜等应激刺激,同时,给药组灌胃,正常对照组与模型组同体积生理盐水灌胃,每日1次,连续28 d。Lab Ex多因子方法检测细胞因子的表达情况。结果:与正常对照组相比,模型组大鼠白介素-1ɑ(interleukin-1ɑ,IL-1ɑ)、白介素-2(interleukin-6,IL-2)等炎性细胞因子以及巨噬细胞趋化因子-1(monocyte chemoattractant protein-1,MCP-1)、重组趋化因子(chemokine c-motif ligand 5,CCL5)等趋化因子的表达水平升高(P<0.05),同时,白介素-4(interleukin-4,IL-4)、白介素-10(interleukin-10,IL-10)等抗炎细胞因子和巨噬细胞集落刺激因子(macrophage colony-stimulating factor, M-CSF),血管内皮生长因子(vascular endothelial growth factor, VEGF)等生长因子的表达水平降低(P<0.05);与模型组相比较,GTS治疗组及阳性药物对照组大鼠以上指标的表达水平出现逆转(P<0.05)。结论:GTS通过降低CUMS抑郁模型大鼠中枢神经系统PFC区趋化因子、炎症因子的表达水平发挥抗抑郁作用。

关键词： 强直性脊柱炎   TBNK淋巴细胞亚群   细胞因子  

摘要： 目的探讨强直性脊柱炎(AS)患者外周血TBNK淋巴细胞亚群及细胞因子变化特征,为AS临床诊疗提供新的实验室指标。方法选择125例AS患者作为AS组,其中,HLA-B27阳性患者106例,HLA-B27阴性患者19例,随机选取同期127名健康体检者作为对照组,空腹采集静脉血,采用流式细胞仪测定淋巴细胞亚群CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞、B细胞等指标和细胞因子,分析强直性脊柱炎患者外周血TBNK淋巴细胞亚群及细胞因子的变化特征。结果AS组CD4^(+)T细胞占比、CD4^(+)/CD8^(+)明显高于对照组(P<0.05),CD8^(+)T细胞、NK细胞、NKT细胞占比则低于对照组(P<0.05);AS患者组淋巴细胞亚群绝对值均低于对照组(P<0.05)。AS患者组血清IL-6和TNF-α水平更高,TNF-α和IL-6水平与CD4^(+)T细胞呈较强的正相关关系,与CD4^(+)T细胞升高相符。HLA-B27阳性与HLA-B27阴性AS患者淋巴细胞亚群及细胞因子检测结果比较差异无统计学意义(P>0.05)。AS患者BASDAI指数与CD4^(+)T细胞占比、CD4^(+)/CD8^(+)、IL-6和TNF-α水平呈较强的正相关关系。结论强直性脊柱炎患者外周血T淋巴细胞亚群CD4^(+)T细胞占比、CD4^(+)/CD8^(+),细胞因子IL-6和TNF-α水平对AS患者的鉴别诊断和治疗监测具有临床意义。