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关键词： 白血病,T细胞   β-肾上腺素受体   儿童   预后  

摘要： 背景β-肾上腺素受体(β-AR)与部分肿瘤的发生、发展密切相关,但急性T淋巴细胞白血病(T-ALL)细胞上是否存在β-AR的表达,且β-AR是否与T-ALL的预后及危险度相关,目前国内外报道较缺乏。目的明确T-ALL患儿白血病细胞上β-AR的表达情况,并分析β-AR对T-ALL患儿危险度及预后的影响。方法数据库查询β1-AR、β2-AR及β3-AR在白血病细胞及其他恶性肿瘤上的表达水平,同时查询β1-AR、β2-AR及β3-AR的表达水平对肿瘤预后的影响,并归纳总结数据。收集2019年—2022年于遵义医科大学附属医院治疗的T-ALL患儿的临床资料及骨髓标本,共40例,根据诊治情况及疗效分为T-ALL初诊组及T-ALL缓解组,其中T-ALL初诊组23例,T-ALL缓解组17例;同时收集15例非血液疾病患儿的临床资料及骨髓标本作为对照组。将T-ALL初诊组患儿分为中危亚组(9例)及高危亚组(14例)。同时将T-ALL初诊组患儿按预后结果进行分组,死亡及复发者为预后不良亚组(10例),疗效好并完全缓解者为预后良好亚组(13例)。收集患儿的临床资料。采用免疫印迹试验(Western blot)检测T-ALL细胞β-AR表达。采用Pearson相关性分析或Spearman秩相关检验分析β-AR与T-ALL患儿危险程度的相关性。采用多因素Logistic回归分析探究T-ALL患儿高危的影响因素。结果数据库检索结果发现:β1-AR在前列腺癌中表达水平较高,β2-AR在血液及前列腺等相关恶性肿瘤中表达水平较高,β3-AR在恶性肿瘤中的表达水平极低。与正常血液组织比较,急性髓系白血病血液组织β-AR基因的表达较高,主要以β2-AR基因表达为主,其次是β1-AR基因,而β3-AR基因表达水平较低。β1-AR基因可影响宫颈癌、肺鳞状细胞癌、胰腺癌、肉瘤及黑色素瘤患者的生存率,β2-AR基因可影响肾癌、肺腺癌及胸腺癌患者的生存率,β3-AR基因可影响肾透明细胞癌患者的生存率。Western blot结果显示,T-ALL初诊组β1-AR、β2-AR、β3-AR蛋白表达水平高于对照组、T-ALL缓解组(P<0.05)。高危亚组β3-AR高于中危亚组(P<0.05)。多因素Logistic回归分析结果显示,β3-AR升高(OR=7.036,95%CI=1.244~39.783,P=0.027)及化疗15 d后骨髓中有白血病细胞(OR=10.667,95%CI=1.035~109.941,P=0.047)是T-ALL患儿高危的危险因素,β3-AR升高(OR=8.447,95%CI=1.557~45.819,P=0.013)是T-ALL患儿预后不良的危险因素。相关性分析结果显示,β2-AR与白血病计数、初诊骨髓白血病细胞比例、化疗15 d骨髓白血病细胞呈正相关,β3-AR与T-ALL患儿危险度、预后呈正相关(P<0.05)。结论T-ALL患儿白血病细胞上存在β-AR的异常高表达,且β-AR表达水平的下降可作为T-ALL患儿缓解的指标。此外,β3-AR异常高表达是T-ALL患儿发生高危及预后不良的独立危险因素。

关键词： kidney transplantation   ABO-histocompatibility   ABO histo-blood groups   ABO-incompatible transplantation   multiplex assay   hemagglutination titers   transplant inequities   ABO-A2i   ABO-A2-incompatible   DTT   dithiothreitol   HLA   human leukocyte antigen   MFI   mean fluorescence intensity   OPTN   Organ Procurement and Transplantation Network   PBS   phosphate-buffered saline  

摘要： Kidney transplantation from ABO-A2 donors into ABO-O and ABO-B recipients can alleviate inequitable transplant access created by ABO demographics. ABO-A2-incompatible (ABO-A2i) eligibility is determined by anti-A hemagglutination titers. However, titers do not distinguish antibodies specific for A-II glycans, the sole A-antigen subtype in vascular endothelium, from other anti-A antibodies. We examined whether reliance on anti-A titers unnecessarily limited ABO-A2i transplants for candidates with low anti-A-II levels. We created a single-antigen bead immunoassay for ABO antibodies, confirmed the specificity and reproducibility, and demonstrated the ability to detect anti-A and anti-B glycan subtype-specific antibodies in healthy control sera. We then measured subtype-specific anti-A antibodies in original sera from ABO-B and ABO-O candidates who had been previously evaluated for ABO-A2i eligibility. Anti-A-II levels in candidates who had been deemed ineligible (anti-A titers >4) were compared to eligible candidates (anti-A titers ≤4) who had subsequently received ABO-A2i kidneys. Of 141 candidates, 75 (53%) were ineligible; 66 (47%) were eligible and received ABO-A2 kidneys. Retesting original sera, 55% (41/75) of ineligible candidates had anti-A-II levels comparable to eligible candidates. Anti-A titers did not reflect anti-A-II levels. Our ABO antibody assay reproducibly measures graft-specific anti-A-II antibodies, providing information beyond anti-A titers that may increase transplant access for ABO-B and ABO-O candidates.

摘要： Tumor necrosis factor (TNF) signaling determines the cell's fate by promoting either survival or cell death via apoptosis, necroptosis or pyroptosis. Excessive or chronic cell death by TNF was shown to drive inflammatory pathologies, highlighting the importance of the mechanisms that normally block TNF cytotoxicity. This study investigates the role of TAB2, an adaptor protein traditionally linked to TAK1 activation in the TNF pathway. Contrary to expectations, TAB2 deficiency did not impair TAK1-dependent NF-κB or MAPK signaling, nor did it affect TAK1- and IKK-dependent inhibitory phosphorylation of RIPK1 in TNFR1 complex I, indicating that TAK1 remains functional in absence of TAB2. Still, TAB2 deficiency switches the TNF response from survival to apoptosis, demonstrating a crucial TAK1-independent pro-survival function of TAB2 in the pathway. This switch was absent in TAB3-deficient conditions, highlighting a non-redundant function of TAB2. We show that TAB2 is an integral part of TNFR1 complex II, limiting the abundance of the cytotoxic complex through direct association. The ubiquitin-binding NZF domain of TAB2 is critical for this function as cells expressing a NZF-deficient mutant switched the TNF response towards apoptosis, while not affecting TAK1-mediated signaling. Moreover, we found that the NZF domain of TAB2 also represses TNF-mediated necroptosis in conditions of Caspase-8 inhibition, thereby showing that TAB2 represses two different cell death modalities in the TNF pathway by limiting the abundance of two variations of the cytotoxic complex II. Together, our results reveal the existence of a new cell death checkpoint in the TNF pathway that is controlled by TAB2, through a mechanism independent of its established function in TAK1 recruitment and activation.

关键词： 三疣梭子蟹   原肌球蛋白   线性表位   预测  

摘要： 目的 研究三疣梭子蟹(Portunus trituberculatus)原肌球蛋白(tropomyosin,TM) Por t 4的理化性质、二级结构、B细胞和T细胞的线性表位。方法 利用生物信息学软件UniProt数据库、EXPASY、DNAstar软件、SOPMA、Immunomedicine Group、ABCpred、IEDB、SYFPEITHI、Net MHCII和Net MHCIIpan在线工具分析Por t 4的理化性质、蛋白二级结构并预测B细胞表位和T细胞表位。结果 Por t 4为亲水性蛋白,二级结构以α-螺旋为主,无复杂的空间结构,潜在的B细胞表位有^(23)NTLEQQN^(29)、^(36)AEKTEEEIRAT^(46)、^(134)SLS^(136)、^(177)ERAEERAE^(184)、^(210)SEEKANQRE^(218)、^(244)RSV^(246)和^(262)NEKEKY^(267),潜在的T细胞表位有^(82)EGEVAALNRRIQLL^(95)和^(222)KEQIKTLANKLKAA^(235)。结论 本研究通过生物信息学软件分析,在Por t 4蛋白中预测得到7个优势B细胞线性表位和2个优势T细胞线性表位,为进一步开展Por t 4的过敏机制研究提供理论依据。

关键词： 急性胰腺炎   低分子肝素   复方丹参注射液   肠黏膜屏障功能   肠道菌群   胰腺功能评分  

摘要： 目的分析急性胰腺炎患者接受低分子肝素联合复方丹参注射液治疗后对其肠黏膜屏障功能、肠道菌群以及白细胞介素-17(IL-17)、成纤维细胞生长因子-21(FGF-21)的影响。方法90例急性胰腺炎患者作为研究对象,按照单盲法分为丹参组、肝素组和联合组,各30例。丹参组接受复方丹参注射液治疗,肝素组接受低分子肝素治疗,联合组采用低分子肝素联合复方丹参注射液治疗。对比三组临床疗效、中医证候积分、肠黏膜屏障功能指标、肠道菌群指标、IL-17、FGF-21和胰腺功能评分。结果联合组治疗总有效率96.67%高于丹参组的66.67%和肝素组的70.00%(P<0.05)。联合组腹满硬痛拒按、大便燥结、胸脘痞闷不舒、恶心呕吐、小便短赤积分分别为(0.74±0.08)、(0.68±0.07)、(0.75±0.09)、(0.77±0.09)、(0.62±0.04)分,低于丹参组的(2.04±0.15)、(1.95±0.14)、(2.11±0.19)、(2.06±0.14)、(1.94±0.14)分和肝素组的(2.09±0.16)、(1.99±0.15)、(2.07±0.18)、(2.09±0.15)、(1.91±0.13)分(P<0.05)。治疗后,三组内毒素、二胺氧化酶、D-乳酸明显降低,且联合组内毒素(0.46±0.02)EU/ml、二胺氧化酶(2.10±0.18)U/ml、D-乳酸(3.81±0.36)mmol/L低于丹参组的(0.92±0.07)EU/ml、(3.09±0.28)U/ml、(6.86±0.66)mmol/L和肝素组的(0.95±0.08)EU/ml、(3.11±0.29)U/ml、(6.92±0.67)mmol/L(P<0.05)。治疗后,三组肠球菌、大肠埃希菌下降,乳酸杆菌、双歧杆菌上升,且联合组肠球菌、大肠埃希菌低于丹参组和肝素组,乳酸杆菌、双歧杆菌高于丹参组和肝素组(P<0.05)。治疗后,三组IL-17、FGF-21均下降,且联合组IL-17(152.58±13.46)pg/ml、FGF-21(450.25±42.05)ng/ml低于丹参组的(192.24±17.18)pg/ml、(493.63±47.21)ng/ml和肝素组的(192.39±17.20)pg/ml、(494.05±47.24)ng/ml(P<0.05)。治疗后,三组CT严重度指数(CTSI)评分、急性生理与慢性健康状况评分Ⅱ(APACHE-Ⅱ)评分均下降,且联合组CTSI评分(3.77±0.35)分、APACHE-Ⅱ评分(5.67±0.54)分低于丹参组的(5.84±0.56)、(9.09±0.88)分和肝素组的(5.80±0.55)、(9.12±0.89)分(P<0.05)。结论急性胰腺炎患者接受低分子肝素联合复方丹参注射液治疗,患者的肠道菌群、肠黏膜屏障功能、胰腺功能、IL-17、FGF-21明显改善,治疗效果较高。

摘要： L’intelligenza artificiale ha rivoluzionato l’analisi delle immagini ecografiche di noduli tiroidei, automatizzando la segmentazione, passaggio chiave per l’estrazione delle caratteristiche radiomiche e la stratificazione del rischio di malignità. La rassegna descrive i principali modelli di segmentazione automatica, analizzandone limiti e prospettive di integrazione clinica.

关键词： CFTR   COPD   Polymorphism   Cystic fibrosis   IL-8   RFFL   Ubiquitin ligase   Pyocyanin  

摘要： Chronic exposure to environmental pathogens and pollutants can impair CFTR chloride channel function, contributing to chronic obstructive pulmonary disease (COPD). Our previous study demonstrated that pyocyanin (PYO), a COPD-associated pathogen factor, significantly reduces the functional expression of R75Q- or M470VCFTR, two CFTR polymorphisms found in COPD patients, leading to increased IL-8 production in airway epithelial cells (AEC). In this study, we report that inhibition of RFFL, a ubiquitin ligase that targets CFTR mutants for removal from the plasma membrane (PM), mitigates excessive IL-8 production in AECs expressing R75Q- or M470V-CFTR, even in the presence of PYO. RFFL knockdown (KD) enhanced the functional PM expression of R75Q- or M470V-CFTR under PYO exposure, although it did not prevent PYO-induced CFTR downregulation. Our results indicate that RFFL likely regulates constitutive IL-8 production independently of CFTR, while also modulating pathogen-induced IL-8 expression through a CFTR-dependent mechanism. This highlights the potential of RFFL inhibitors to enhance CFTR function and reduce IL-8 secretion, even amid chronic exposure to environmental pathogens and pollutants, underscoring RFFL inhibition as a promising therapeutic approach for COPD management.

关键词： natural killer cells   MHC   comparative immunology/evolution   antigens/peptides/epitopes   KIR   killer-cell immunoglobulin-like receptor   MHC   major histocompatibility complex   NK   natural killer   PDB   Protein Data Bank   VDW   van der Waals  

摘要： HLA class I alleles of archaic origin may have been retained in modern humans because they provide immunity against diseases to which archaic humans had evolved resistance. According to this model, archaic introgressed alleles were somehow distinct from those that evolved in African populations. Here, we show that HLA-B∗73:01, a rare allotype with putative archaic origins, has a relatively rare peptide binding motif with an unusually long-tailed peptide length distribution. We also find that HLA-B∗73:01 combines a restricted and unique peptidome with high-cell surface expression, characteristics that make it well-suited to combat one or a number of closely related pathogens. Furthermore, a crystal structure of HLA-B∗73:01 in complex with KIR2DL2 highlights differences from previously solved structures with HLA-C molecules. These molecular characteristics distinguish HLA-B∗73:01 from other HLA class I alleles previously investigated and may have provided early modern human migrants that inherited this allele with a selective advantage as they colonized Europe and Asia.

关键词： 中性粒细胞/淋巴细胞   血小板/淋巴细胞   维持性血液透析   抑郁  

摘要： 目的:探讨中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)对维持性血液透析(MHD)患者抑郁的影响及预测价值。方法:选取2023年4月-2024年9月在本院接受规律MHD治疗的287例慢性肾脏病患者,依据汉密尔顿焦虑抑郁量表(HADS)评分分为非抑郁组(174例)和抑郁组(113例)。收集两组患者一般资料(包括家庭收入)及实验室指标,比较组间差异;采用多因素Logistic回归分析MHD患者抑郁的独立危险因素。结果:抑郁组家庭收入显著低于非抑郁组(P<0.05);抑郁组白细胞计数(WBC)、中性粒细胞计数(NEU)、血小板(PLT)、NLR及PLR水平均显著高于非抑郁组,淋巴细胞计数(LYM)水平显著低于非抑郁组(P<0.05或P<0.01)。多因素Logistic回归分析显示,家庭收入较低(4000-8000元/月vs<4000元/月:OR=0.317,95%CI 0.148-0.678,P=0.003)、NLR升高(OR=1.299,95%CI 1.187-2.875,P=0.029)及PLR升高(OR=1.011,95%CI 1.004-1.018,P=0.003)是MHD患者抑郁的独立危险因素。结论:家庭低收入、NLR及PLR升高与MHD患者抑郁密切相关,可作为早期识别MHD患者抑郁风险的潜在指标。

关键词： Tumor necrosis alpha inhibitors   infective endocarditis   prosthetic aortic valve   surgical aortic valve replacement   transesophageal echocardiography  

摘要： Tumor necrosis factor-alpha (TNF-α) inhibitors and other biologics used for autoimmune diseases are associated with low-grade immunosuppression. Treatment with these and the presence of prosthetic mechanical cardiac valves both increase the risk of infective endocarditis (IE). However, evidence on the risk of prosthetic valve endocarditis (PVE) among patients treated with TNF-α inhibitors is limited. This study reports a 41-year-old man with a prosthetic aortic valve who was on treatment with golimumab and presented with low-grade fevers and positive blood cultures for . Transesophageal echocardiogram revealed vegetations adjacent to the valve sewing ring and an inflammatory phlegmon in the right atrium, leading to a diagnosis of prosthetic valve endocarditis. The patient was referred to a higher level of care center and underwent urgent surgical intervention. The study highlights that TNF-α inhibitors and other biologics may increase the risk of prosthetic heart valve endocarditis and the importance of early imaging for diagnosis.