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关键词： 中医证型   IL-6   IFN-γ   原发性肺癌   化疗敏感性   预后   临床研究  

摘要： 目的:探讨中医证型、血清白细胞介素-6(IL-6)和干扰素-γ(IFN-γ)在评估原发性肺癌患者化疗敏感性、预后中的价值。方法:选取2019年4月—2021年7月在湖南中医药大学第二附属医院确诊的原发性肺癌患者120例,根据是否存在化疗耐药分为耐药组(n=48)和敏感组(n=72)。随访3年,根据患者存活情况分为预后良好组(存活,n=55)和预后不良组(死亡,n=65)。比较各组中医证型分布及血清IL-6、IFN-γ水平。结果:不同化疗敏感性患者中医证型分布比较,耐药组气滞血瘀型占比明显高于敏感组(P<0.05);敏感组阴虚热毒型和气阴两虚型明显高于耐药组(P<0.05);耐药组患者血清IL-6水平明显高于敏感组,IFN-γ水平明显低于敏感组(P<0.05);预后不良组患者气滞血瘀型占比明显高于预后良好组(P<0.05);预后不良组患者血清IL-6水平明显高于预后良好组,IFN-γ水平明显低于预后良好组(P<0.05)。结论:综合评估中医证型、血清IL-6和IFN-γ水平,有助于临床医生更准确地判断原发性肺癌患者的化疗敏感性和预后。

摘要： Organ transplantation is a lifesaving procedure, with 50,000 transplants happening every year in the United States. However, many patients harbor antibodies and B cells directed against allogeneic human leukocyte antigen (HLA) molecules, notably HLA-A2, greatly decreasing their likelihood of receiving a compatible organ. Moreover, antibody-mediated rejection is a significant contributor to chronic transplant rejection. Current strategies to desensitize patients non- specifically target circulating antibodies and B cells, resulting in poor efficacy and complications. Regulatory T cells (Tregs) are immune cells dedicated to suppressing specific immune responses by interacting with both innate and adaptive immune cells. Here, we genetically modified human Tregs with a chimeric anti-HLA antibody receptor (CHAR) consisting of an extracellular HLA-A2 protein fused to a CD28-CD3zeta intracellular signaling domain, driving Treg activation upon recognition of anti-HLA-A2 antibodies on the surface of alloreactive B cells. We find that HLA-A2 CHAR Tregs get activated specifically by anti-HLA-A2 antibody-producing cells. Of note, HLA-A2 CHAR activation does not negatively affect Treg stability, as measured by expression of the Treg lineage transcription factors FOXP3 and HELIOS. Interestingly, HLA-A2 CHAR Tregs are not cytotoxic towards anti-HLA-A2 antibody-producing cells, unlike HLA-A2 CHAR modified conventional CD4 T cells. Importantly, HLA-A2 CHAR Tregs recognize and significantly suppress high affinity IgG antibody production by B cells from HLA-A2 sensitized patients. Altogether, our results provide proof-of-concept of a new strategy to specifically inhibit alloreactive B cells to desensitize transplant recipients.

关键词： T-cell receptor triggering   T-cell receptor-ligand interactions   the structure of MHC presented peptides   well-tempered metadynamics and supercomputing  

摘要： A high-resolution crystal structure of stimulatory peptide-major histocompatibility complex (pMHC) ligands bound to T cell receptor (TCR) revealed different conformations of the two peptides at positions P6 and V7 compared to the conformation of the same peptides presented by unliganded MHC. Supercomputer simulations and a well-tempered metadynamics approach revealed several metastable noncanonical TCR-pMHC interactions that depend on the conformation of the MHCbound peptides. The diversity of metastable states was significantly more represented in the signaling TCR-pMHC complex. These findings suggest that TCR-pMHC recognition can be informed by a conformation of peptide presented by MHC that notably influences the orientation of a TCR-recognizing pMHC ligand. It appears that TCRs bound to stimulatory pMHC possess a significantly higher degree of freedom to assume various metastable TCR orientations, which are distinct from canonical docking. In contrast, TCR interacting with nonstimulatory pMHC ligand revealed markedly less metastable noncanonical interactions and disengaged from the pMHC. This suggests that productive TCR-mediated signaling may depend on noncanonical interactions between TCRs and pMHC, either facilitating early recognition events or providing new contacts for catch-bond formation. Our discovery can inform future attempts to simulate the catch-bond formation mechanism in TCR-pMHC recognition, allowing the formation of new bonds mediating alternative peptide presentation.

关键词： CD4(+) T Cells   Viral Infection   IFN-gamma   B-cell Responses  

摘要： CD4(+) T cells play a critical role in supporting antiviral humoral and cellular immune responses. Although these responses often coexist, one can sometimes dominate at the expense of the other. For instance, lymphocytic choriomeningitis virus (LCMV) induces a strong cellular immune response but generates a suboptimal neutralizing antibody (nAb) response, hindering viral clearance and enabling persistent infection. Recent findings indicate that this skewed preference toward cellular immunity is determined already during the differentiation of CD4(+) T cells. Specifically, subcutaneous (s.c.) LCMV infection predominantly induces T-bet(+) T helper 1 (T(H)1) differentiation while largely neglecting T follicular helper (T-FH) differentiation, a key driver of humoral immunity. Here, we investigated the mechanisms responsible for this impaired T-FH differentiation. We found that T-bet(+) cells induced by s.c. LCMV infection are heterogeneous and encompass a terminally differentiated T(H)1 subset expressing Granzyme-B (GzmB) and a Tcf-1(+) subset that retains the potential for T-FH differentiation but that does not express CXCR5 and other mature T-FH markers. Interestingly, T cell-derived IFN-gamma facilitated the proliferation of the GzmB(+) subset and inhibited Tcf-1(+) cells' progression into T-FH. The suppression of T-FH cells by IFN-gamma was not directly mediated through CD4(+) T cells but rather involved another cell type, likely dendritic cells. Consistently, inhibition of IFN-gamma enabled robust T-FH differentiation, formation of germinal centers and increased antibody production. Our study provides novel insights into the mechanisms inhibiting nAb production in response to viruses and lays a foundation for the development of advanced vaccine strategies.

关键词： 慢性放射性直肠炎   鹅掌楸苷   细胞因子  

摘要： 目的探究鹅掌楸苷对慢性放射性直肠炎的保护作用及其可能机制。方法将32只雌性C57/BL小鼠按照随机原则分为空白对照组、模型组、鹅掌楸苷灌胃组以及鹅掌楸苷灌肠组四组,每组8只小鼠。采用10 Gy X射线单次局部辐照小鼠盆腔区域建立慢性放射性直肠炎模型,鹅掌楸苷灌胃组和鹅掌楸苷灌肠组分别予以100 mg/kg鹅掌楸苷灌胃或灌肠,模型组与空白对照组予以等体积生理盐水灌胃,每周1次,持续8周。观察各组小鼠体重与排便情况,评估小鼠生存情况并评分,绘制生存曲线;HE染色观察小鼠肠组织病理学变化并统计病理评分;ELISA检测小鼠血清中促炎因子肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ),抑炎因子白细胞介素-10(IL-10)、转化生长因子-β1(TGF-β1)水平。结果鹅掌楸苷灌胃组和灌肠组小鼠生存率均高于模型组(P<0.05),其中,鹅掌楸苷灌胃组与灌肠组小鼠体重与排便情况均优于模型组(P<0.05);与模型组相比,鹅掌楸苷灌胃组和灌肠组小鼠血清中促炎因子IFN-γ、TNF-α水平明显降低,抑炎因子TGF-β1、IL-10水平明显升高(P<0.05)。结论鹅掌楸苷能有效改善小鼠慢性放射性直肠炎的炎症反应、保护直肠组织,提高慢性放射性直肠炎小鼠生存率,改善小鼠辐照后生存情况,其作用机制可能与鹅掌楸苷调控炎症相关细胞因子的释放有关。

关键词： 鼻腔鼻窦黏膜黑色素瘤   肿瘤浸润淋巴细胞   CD4   CD8   CD20  

摘要： 目的总结鼻腔鼻窦恶性黑色素瘤(MMNS)的临床病理学特点,提出MMNS预后预测因子;观察并分析CD4、CD8、CD20的表达、定位以及其与预后的关系。方法回顾分析87例MMNS患者临床病理资料,总结其临床病理特征;采用EnVision免疫组织化学(IHC)染色方法观察CD4、CD8、CD20在MMNS中的表达及定位情况。结果87例MMNS患者中,男性46例,女性41例,年龄在43至81岁之间,中位年龄60岁。鼻腔合并鼻窦及周围组织浸润、肿瘤体积大及AJCC分期高则预后差(P<0.05);统计结果显示性别、年龄、组织学类型、黑色素颗粒、核分裂象等与生存期之间无显著相关性(P>0.05)。CD4^(+)、CD8^(+)及CD20^(+)肿瘤浸润淋巴细胞(TILs)免疫亚型在瘤内间质与肿瘤基底分组之间差异均有统计学意义(P<0.05),且瘤内间质CD4^(+)、CD8^(+)及CD20^(+)TILs的阳性计数的高低与肿瘤基底部TILs密度呈正相关(P<0.01)。不管是瘤内间质还是肿瘤基底部CD20^(+)B细胞与CD4^(+)、CD8^(+)T细胞分布于同一区域,为较均匀的掺杂分布,CD20^(+)B细胞没有中心聚集形成三级淋巴结构的趋势。不同亚型分组的总生存期之间的差异无统计学意义。结论不论是瘤内间质还是肿瘤基底部间质,CD20^(+)B细胞的数量均明显少于CD4^(+)、CD8^(+)T细胞,不能形成三级淋巴结构,与皮肤恶性黑色素瘤不同,可能是MMNS预后差的一个原因。

关键词： 轻度胃肠炎伴婴幼儿良性惊厥   神经元特异性烯醇化酶   一氧化氮   白细胞介素-1   白细胞介素-6  

摘要： 目的探讨轻度胃肠炎伴婴幼儿良性惊厥(BICE)患儿肠道菌群特征与血清神经元特异性烯醇化酶(NSE)、一氧化氮(NO)、白细胞介素-1(IL-1)、白细胞介素-6(IL-6)的临床意义。方法选择2022年11月至2023年11月榆林市第一医院接诊的BICE患儿40例作为研究组,选择40例轻度胃肠炎患儿作为对照组。比较两组患儿肠道菌群、血清NSE、NO、IL-1、IL-6水平,并比较不同病情程度、复发情况BICE患儿的肠道菌群、血清NSE、NO、IL-1、IL-6水平。采用Pearson相关分析法分析BICE患儿肠道菌群特、血清NSE、NO、IL-1、IL-6与病情和复发情况的相关性。结果研究组患儿道菌群肠球菌、大肠杆菌、乳酸杆菌、双歧杆菌水平均低于对照组,血清NSE、NO、IL-1、IL-6均高于对照组,差异有统计学意义(P<0.05)。严重组BICE患儿肠道菌群肠球菌、大肠杆菌、乳酸杆菌、双歧杆菌水平均低于普通组,血清NSE、NO、IL-1、IL-6均高于普通组,差异有统计学意义(P<0.05);复发组BICE患儿肠道菌群肠球菌、大肠杆菌、乳酸杆菌、双歧杆菌水平均低于未复发组,血清NSE、NO、IL-1、IL-6均高于未复发组,差异有统计学意义(P<0.05);Pearson相关分析显示,BICE患儿肠道菌群肠球菌、大肠杆菌、乳酸杆菌、双歧杆菌与病情和复发情况均呈负相关,BICE患儿血清NSE、NO、IL-1、IL-6与病情和复发情况均呈正相关(P<0.05)。结论BICE患儿肠道菌群、血清NSE、NO、IL-1、IL-6变化与病情程度和复发密切相关,监测这些指标有助于采取临床早期干预和治疗。

关键词： 变应性鼻炎   温督法   鼻部症状总评分表   IFN-y   IL-5   EOS  

摘要： 探究变应性鼻炎患者,应用温鼻益肺方联合督脉铺灸治疗的价值。方法 选取2024年1月—2024年12月江西省人民医院耳鼻喉门诊肺气虚寒证变应性鼻炎病例作为研究对象,共计60例,采取单盲和随机分配的方法,分为治疗组(n=30,温督法)、对照组(n=30,普通针刺),分析其在鼻部症状总评分表(TNSS)、疗效以及白介素-5(IL-5)、γ-干扰素(IFN-γ)、鼻腔黏膜嗜酸性粒细胞(EOS)水平情况。结果 TNSS评分、IFN-y,IL-5,EOS的水平情况方面,两组治疗前差异无统计学意义(P>0.05),但治疗后,治疗组指标改善幅度均高于对照组(P<0.05);治疗后,治疗组疗效高于对照组(х2=6.405,P=0.011;P<0.05)。结论 临床患有变应性鼻炎的患者中,应用温鼻益肺方联合督脉铺灸治疗的价值较为理想,能够显著增强其临床疗效,降低其TNSS评分,促进IFN-y,IL-5,EOS水平的改善,具有临床应用意义。

关键词： HLA-B   新等位基因   二代测序   纳米孔测序   碱基突变  

摘要： 目的:区分人类白细胞抗原(HLA)模棱两可的基因分型结果,鉴定HLA-B新等位基因,并分析其核苷酸序列。方法:利用基于Ion Torrent S5平台的二代测序技术(NGS)对2022年2076例浙江省脐带血库样本进行HLA入库分型检测,发现1例含碱基突变的模棱两可组合样本,选择基于纳米孔技术平台的三代测序技术(TGS)对其进行鉴定。结果:HLA-B位点经NGS检测分型结果显示为HLA-B*46:18,54:06/46:01,54:XX(含碱基突变)组合,经纳米孔测序鉴定结果为HLA-B*46:01,54:XX(含碱基突变)。HLA-B*54:XX与同源性最高的HLA-B*54:01:01:01相比,第6外显子1014位碱基T>C,并未引起任何氨基酸的改变。新等位基因序列已递交给GenBank数据库(OP853532)。结论:应用纳米孔测序技术区分了1例NGS方法产生的模棱两可结果,并成功鉴定了HLA-B新等位基因。该新等位基因被世界卫生组织HLA因子命名委员会正式命名为HLA-B*54:01:11。