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关键词： CD45 on CD33br HLA-DR   cholecystitis   glycine levels   Mendelian randomization  

摘要： Over the past 2 decades, the prevalence of cholecystitis has increased significantly, a trend believed to be influenced by improvements in quality of life and changes in lifestyle habits. However, the precise etiology of cholecystitis remains unclear. Although gallstones are commonly associated with this condition, recent studies suggest that immune cells also play a critical role in their development. This study investigated the relationship between cholecystitis and CD45 on CD33br HLA-DR+ immune cells, focusing on the mediating role of glycine levels, using Mendelian randomization (MR). The primary analytical approach employed was inverse variance weighting (IVW) complemented by additional methods, such as MR-Egger, weighted median, simple mode, and weighted mode. Horizontal pleiotropy and heterogeneity were evaluated to ensure the robustness of the MR findings, and a "leave-one-out" analysis was conducted to explore potential mediating effects. IVW analysis revealed that the association between cholecystitis and CD45 on CD33br HLA-DR+ immune cells yielded an odds ratio of 1.039 (95% confidence interval: 1.012-1.067, P = .004). Mediation analysis further indicated that glycine levels mediated this relationship, with a significant mediating effect of 6.87% (P = .0046). Notably, cholecystitis did not exhibit a reverse causal effect of CD45 on CD33br HLA-DR+ levels (P = .545;IVW odds ratio = 1.044, 95% confidence interval: 0.907-1.201). These findings suggested that the association between CD45 on CD33br HLA-DR+ immune cells and cholecystitis is mediated by glycine levels. This study provides novel insights into cholecystitis pathogenesis, highlighting the potential role of metabolic factors in immune-mediated inflammation. These results offer a new perspective on the underlying mechanisms of cholecystitis and suggest potential metabolic intervention targets for its prevention.

关键词： BNP   IL-6   超声心动图参数   慢性心力衰竭   诊断效能  

摘要： 以慢性心力衰竭(CRF)病例为对象,观察B型脑钠肽(BNP)、白细胞介素-6(IL-6)、超声心动图参数诊断价值。方法 纳入CRF病例(40例,设为CRF组)、健康体检者(40例,设为参照组),均2023.1-2025.1期间就诊于联勤保障部队第970医院。以上病例均行IL-6、BNP测定,及超声心动图检查;观察诊断结果。结果 超声心动图参数统计,CRF组LVEF低于参照组,LVESV、LVEDV、LVESD、LVEDD高于参照组(均P<0.05);血清学指标统计,CRF组IL-6、BNP高于参照组(均P<0.05)。四组不同心功能分级CRF病例各指标比较LVEF、LVEDD,Ⅲ级、Ⅳ级水平高于Ⅰ级、Ⅱ级(P<0.05);Ⅲ级、Ⅳ级比较无意义(均P>0.05);Ⅰ级、Ⅱ级比较无意义(均P>0.05)。LVESV、LVEDV、LVESD、IL-6、BNP比较,均Ⅰ级<Ⅱ级<Ⅲ级<Ⅳ级(均P<0.05)。各项联合检验灵敏度、准确性较各单一指标均更高(均P<0.05)。结论 比较非RF健康体检者,RF病例IL-6、BNP及超声心动图参数均波动明显,且伴随病情加重,各指标波动幅度明显增大。超声心动图参数+BNP+IL-6诊断RF灵敏度、准确性均较高,可为疾病诊断治疗提供科学参考。

关键词： CD8+ T cells   HLA-B44 supertype   HLA-I supertype   immunogenicity   influenza   structural prediction  

摘要： Objectives CD8+ T cells are protective against influenza and there is an interest in designing a future CD8+ T-cell-mediated vaccine. However, a significant challenge is the extensive polymorphism of Human Leukocyte Antigen class I (HLA-I) molecules, the targets of CD8+ T cells. Despite this, HLA supertypes have been defined as a subset of HLA-I molecules sharing similar peptide motif preferences that may present overlapping peptide repertoires. Therefore, selecting immunogenic peptides presented by a range of HLA-I molecules for inclusion in a vaccine may partially overcome the challenge presented by HLA-I *** In this study, we investigated the presentation and immunogenicity of a known HLA-B*44:03-restricted influenza-derived peptide NS1195-203 across the HLA-B44 supertype. Using TFold and AlphaFold2, we predicted the structures of the NS1195-203 bound by the HLA-B44 supertype molecules, including HLA-B*44:02, HLA-B*44:03, HLA-B*40:01, HLA-B*40:01 and HLA-B*45:01. Peripheral blood mononuclear cells (PBMCs) isolated from donors expressing one of these HLA-B44 supertype molecules were used to generate CD8+ T-cell lines against the NS1195-203 peptide and assess its immunogenicity via intracellular cytokine staining *** The structures predicted with TFold and AlphaFold2 of the NS1195-203 peptide in complex with the HLA-B44 allomorphs were overall similar, with some notable differences at the peptide P9-Trp. A polyfunctional NS1195-203-specific CD8+ T-cell response was observed in HLA-B*44:03+ and HLA-B*44:02+ samples;however, minimal responses were observed in the three other HLA-B44+ supertype *** Although HLA molecules from the same supertype may be able to present the same peptide, this will not always result in CD8+ T-cell responses. As such, HLA-I supertypes, defined based on peptide binding motif and presentation, do not include information on immunogenicity and are not currently able to be used on their own to select

关键词： Biochemistry   Cell biology  

摘要： trans-Fatty acids (TFAs) have been associated with various inflammatory diseases, including atherosclerosis and metabolic syndrome, such as metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH). However, the underlying mechanism remains unclear. Here, we show that in response to DNA damage, elaidic acid (EA), a most common TFA, amplifies interleukin-1 receptor (IL-1R) signaling, leading to the promotion of cellular senescence and senescence-associated secretory phenotype (SASP). Upon DNA damage, EA enhanced senescence-associated beta-galactosidase activity and expressions of IL-1 alpha/6/8 through the IL-1R-transforming growth factor-beta-activated kinase 1 (TAK1)-nuclear factor (NF)-kappa B axis in a manner dependent on mammalian target of rapamycin (mTOR). Mechanistically, EA, incorporated into lipid rafts, enhances IL-1R activation and subsequent NF-kappa B signaling, creating a positive feedback loop. EA consumption elevated expressions of SASP factors and cellular senescence in the livers of high-fat diet mice. Our findings provide a mechanistic insight into TFA-related inflammation and disorders, including MASLD/ MASH.

关键词： C/EBPβ   RNA-seq   inflammatory phenotype   osteoarthritis   synovium  

摘要：

关键词： 颈椎病   针灸   推拿   白细胞介素-6   肿瘤坏死因子-α  

摘要： 分析针灸、推拿中医疗法对颈椎病患者各指标的影响。方法 本研究选取2024年1月~12月在本院治疗的颈椎病患者100例,50例对照组接受常规西医治疗,50例研究组接受针灸、推拿中医疗法,比较两组的各项指标和治疗效果。结果 治疗后,两组VAS评分均低于治疗前,且研究组低于对照组;两组JOA评分均高于治疗前,且研究组高于对照组;两组血清IL-6、TNF-α、PGE2水平均低于治疗前,且研究组低于对照组;研究组治疗总有效率高于对照组(P<0.05)。结论 针灸、推拿中医疗法对颈椎病患者来说效果显著。

关键词： 牛乳低聚糖   抗生素相关腹泻   细胞因子   肠道菌群   短链脂肪酸  

摘要： 为了阐明牛乳低聚糖（Bovine Milk Oligosaccharide,BMO）改善抗生素相关腹泻的作用效果，该研究采用动物模型评估了牛乳低聚糖对小鼠腹泻、肠道菌群及代谢功能的影响。采用氨苄西林诱导C57BL/6J小鼠建立抗生素相关腹泻模型，小鼠分为正常对照组（Normal Control,NC），模型组（Model Group,MC）和牛乳低聚糖低、高剂量组（L-BMO组和H-BMO组），干预一周后，分析小鼠腹泻表型、炎症因子水平和紧密连接蛋白表达水平，通过16S rRNA高通量测序和气相色谱分析肠道菌群及短链脂肪酸代谢。结果显示，与MC组相比，牛乳低聚糖高剂量组小鼠体重和水通道蛋白3(Aquaporin 3,AQP3)分别增加了8.65%、128.46%，粪便含水率降低24.51%，血清中白介素（Interleukins,IL）-6、肿瘤坏死因子-α(Tumor Necrosis Factor,TNF-α)和IL-1β降低了26.98%、30.31%和37.60%,IL-10增加了59.21%。同时，牛乳低聚糖组紧密连接蛋白ZO-1、Claudin-1和Occludin的m RNA表达水平显著高于MC组。牛乳低聚糖高剂量组富集了阿克曼菌、拟杆菌、副拟杆菌属和杜伯氏菌，恢复了肠道菌群的平衡。牛乳低聚糖高剂量组小鼠肠道乙酸、丙酸和丁酸的含量是模型组的2.18、2.31和2.25倍。综上，牛乳低聚糖通过改善小鼠腹泻表型、调节肠道炎症反应、促进肠道屏障功能、富集有益菌群并产生短链脂肪酸，展现出改善抗生素相关腹泻的作用。该研究为乳源功能成分在腹泻人群的食品或保健品开发中的应用提供理论支持。

关键词： Saliva   Gingival crevicular fluid   Smoking   Periodontitis   Nonsurgical periodontal debridement   Interleukin-17   Interleukin-35  

摘要： Periodontitis, a chronic inflammatory disease influenced by host-microbiota interactions, poses a significant global health burden. Smoking exacerbates periodontitis progression and impacts treatment outcomes. Interleukin (IL)-17 and IL-35 are key mediators of inflammation, yet their roles in smoking-related periodontitis and responses to non-surgical periodontal treatment (NSPT) remain underexplored. This clinical trial aimed to evaluate the effects of NSPT on salivary and gingival crevicular fluid (GCF) levels of IL-17 and IL-35 in smokers and non-smokers with periodontitis. A total of 55 subjects were divided into three groups: smokers with periodontitis (SP), non-smokers with periodontitis (NSP), and healthy controls (C). All subjects underwent comprehensive periodontal assessments and cytokine level analyses at baseline and four weeks post-NSPT. Saliva and GCF samples were analysed for IL-17 and IL-35 using enzyme-linked immunosorbent assay (ELISA). Statistical analyses evaluated group differences and correlations. After NSPT, both SP and NSP groups exhibited significant improvements in clinical parameters (p < 0.05). Salivary IL-17 and IL-35 levels did not show significant differences between the SP, NSP, and C groups after NSPT (p > 0.05). However, in GCF, IL-17 and IL-35 concentrations significantly increased in both SP and NSP groups following NSPT (p < 0.05). The total amount of GCF IL-17 decreased significantly only in the NSP group after NSPT (p < 0.05), while the total amount of GCF IL-35 increased significantly in both SP and NSP groups (p < 0.05). Strong correlations between IL-17 and IL-35 levels in both saliva and GCF were observed. NSPT modulates inflammatory and anti-inflammatory cytokine profiles, promoting improved clinical outcomes. The impact of smoking on cytokine responses highlights the need for further research to elucidate the mechanisms underlying these cytokine modulations and their role in periodontal therapy. Trial registration Clinic

关键词： parasite-mediated selection   pathogen recognition   reproductive success   corynebacterium   quantitative PCR   black-legged kittiwake  

摘要： The major histocompatibility complex (MHC) is a gene cluster essential for pathogen recognition in jawed vertebrates. It encompasses the MHC class I genes which primarily recognize intracellular parasites, and the MHC class II genes which primarily recognize extracellular parasites. In wild birds, most studies investigating associations between MHC variants and parasites have been carried out in passerines, and have repeatedly shown that specific MHC class I variants provide resistance to intracellular haemosporidian parasites. In contrast, research on the associations between MHC variants and parasites in non-passerine birds remains limited. In this study, we examined the association between MHC-IIB supertypes and the bacterial load of a sexually transmitted bacterium (named C34) in the black-legged kittiwake (Rissa tridactyla), a genetically monogamous seabird. We focused on MHC class II genes because extracellular parasites are particularly prevalent in non-passerines and may therefore exert strong selection on the studied host. We found that females with lower C34 load had better reproductive performance, and higher probability to carry the MHC-IIB supertype SUP6. In contrast, in males, we observed a positive association between C34 load and reproductive performance, but no association between C34 load and MHC-IIB supertypes. While sexually transmitted diseases are not expected to be a strong selective force in genetically monogamous species, our study suggests that C34 might exert a selective pressure on the evolution of the MHC-IIB. Therefore, further research should explore the influence of sexually transmitted diseases on the reproductive biology of genetically monogamous species.

关键词： 贝林妥欧单抗   异基因造血干细胞移植   MRD阳性   急性B淋巴细胞白血病  

摘要： 目的：探索有效治疗策略，以降低异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT前微小残留病（minimal residual disease,MRD）阳性急性B淋巴细胞白血病（acute B-cell lymphocyte leukemia,B-ALL）患者移植后高复发风险。方法：回顾性分析陆军军医大学第二附属医院血液病医学中心2022年11月至2024年11月10例移植前MRD阳性B-ALL患者，中位年龄30（7～56）岁，男性4例，女性6例，4例无关供者移植，6例亲缘间单倍体移植。10例患者均给予贝林妥欧单抗(≥45 kg,28μg/d,14 d;<45 kg,5μg·m-2·d-1,14 d),7 d之内桥接异基因造血干细胞移植预处理。结果：10例患者经贝林妥欧单抗治疗后MRD均转阴，造血干细胞移植后100%供者造血重建，中性粒细胞重建中位时间12（9～22）d，血小板重建中位时间13.5（9～22）d。至2025年1月，中位观察时间14（2～26）个月，2例复发，1例MRD转阳，复发率20%;9例存活，1例死于疾病复发，1例复发后经Car T细胞治疗再次达到完全缓解，MRD转阳患者经白细胞介素-2（interleukin-2,IL-2）治疗MRD再次转阴，目前均存活。治疗期间，有1例患者并发细胞因子释放综合征，1例患者并发新冠病毒感染，1例患者并发带状疱疹及病毒性脑炎，3例患者出现Ⅰ～Ⅱ度急性移植物抗宿主病，4例出现慢性移植物抗宿主病，无移植相关微血栓病变发生。结论：贝林妥欧单抗桥接异基因造血干细胞移植治疗MRD阳性B-ALL可明显降低移植后复发、并发症较少且易控制，后续可通过多中心、随机对照临床研究进一步验证其有效性和安全性。