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关键词： 补肺汤   玉屏风散   环磷酰胺   类风湿关节炎   肺间质病变   血清Ⅱ型肺泡细胞表面抗原   白细胞介素-27  

摘要： 目的：探究补肺汤合玉屏风散加减连环磷酰胺治疗类风湿关节炎肺间质病变的疗效及对血清KL-6、IL-27的影响。方法：选取2024年2月—2025年2月海南医学院第一附属医院住院治疗的类风湿关节炎肺间质病变患者100例，随机数字表奇偶位数分组分为试验组50例与对照组50例。对照组予以注射用环磷酰胺，试验组在对照组的基础上予以补肺汤合玉屏风散加减，两组均连续治疗8周。对比两组中医证候评分、临床疗效、类风湿关节炎疾病活动评分(DAS-28)、呼吸困难症状及肺高分辨率CT(HRCT)评分、血清白细胞介素27(IL-27)、Ⅱ型肺泡细胞表面抗原(KL-6)。结果：治疗后，两组中医证候评分、DAS-28、HRCT评分、血清KL-6、IL-27水平有所降低(P＜0.05)；试验组各项中医证候评分、DAS-28、HRCT评分、血清KL-6、IL-27水平较对照组低(P＜0.05)，总有效率较对照组高(P＜0.05)。对照组不良反应发生率为6.00%与试验组不良反应发生率为4.00%相比无统计学差异(P＞0.05)。结论：补肺汤合玉屏风散加减联合环磷酰胺联合疗法应用于类风湿关节炎肺间质病变中，不仅可增强疗效、改善患者症状、控制肺间质病变进展，其作用机制与下调血清KL-6和IL-27水平具有相关性。

关键词： B细胞   急性淋巴细胞白血病   培门冬酶   急性胰腺炎   危险因素   血常规  

摘要： 目的 分析接受培门冬酶（PEG-ASP）治疗的B细胞急性淋巴细胞白血病（B-ALL）并发胰腺炎（AP）患儿的临床特点及危险因素。方法 回顾性分析2021年1月至2023年2月在医院接受PEG-ASP治疗的272例ALL并发AP患儿的一般资料、临床资料、血常规数据、白蛋白浓度和PEG-ASP累计用量，分析患儿性别、年龄、危险分层、累计培门冬酶剂量、血常规指标、白蛋白浓度与胰腺炎进展的相关性。结果 在272例患儿中，AP发生率为8.5%(23/272),AP与性别、年龄、体质量指数（BMI）、危险分层分布、累计培门冬酶剂量、血红蛋白浓度、血小板计数和单核细胞计数关联无统计学意义（P> 0.05），但与白细胞计数、中性粒细胞计数、淋巴细胞计数、中性粒细胞/淋巴细胞比值、血小板/淋巴细胞比值和白蛋白浓度有显著相关性（P <0.05）。logistic回归分析进一步显示，白细胞计数、中性粒细胞计数、淋巴细胞计数、白蛋白浓度与PEG-ASP相关AP的发生有关（P <0.05）。ROC分析中发现，白细胞计数、淋巴细胞计数和白蛋白浓度可以提示与PEG-ASP相关AP的发生。结论 白细胞计数、中性粒细胞计数、淋巴细胞计数、白蛋白浓度是儿童B-ALL并发培门冬酶相关AP的危险因素。尤其是在血常规检查中观察到白细胞计数、淋巴细胞计数和白蛋白浓度检查中白蛋白浓度的异常有助于早期识别B-ALL并发PEG-ASP相关AP的高危患儿。

摘要： Traditional melon varieties with high value in local markets are grown in the Iberian Peninsula. However, their cultivation is declining, being replaced by modern varieties. Five high quality traditional were selected (‘Piel de Sapo’, ‘Amarillo’, ‘Rochet’, ‘Tendral’ and ‘Blanco’) to modify their fruit morphology in order to make them more appealing for consumer using a set of introgression lines (IL) from the accessions ‘Vedrantais’ (VED, cantaloupe, France), PI 273438 (DUD, Dudaim, Iraq), Ames 24,297 (TRI, wild melon, Pakistan), and PI 124112 (CALC, acidulus, India) in the genetic background of two ‘Piel de Sapo’ cultivars. The ILs contained QTLs that induced round fruits (CALC8-1, DUD4-2, VED11-2), large fruits (TRI05-2), and small fruits (TRI08-2, DUD1-2, DUD4-2). Hybrids between ILs and traditional varieties were studied to verify the effect of ILs in the traditional genetic backgrounds and IL × genetic background (IL × GB) interactions. The ILs with more stable effects were TRI08-2 (reducing fruit weight), TRI05-2 (increasing fruit weight), and CALC8-1 (round shape). ILxGB interactions were also found, mainly in VED11-2 and DUD4-2 for fruit weight. These results allowed us to identify the best ILs to modify fruit morphology in the traditional varieties by breeding programs. Additionally, the identification of IL × GB interactions for some ILs, such as VED11-2 and DUD4-2 for fruit weight provides an experimental system to shed insights into the genetic basis of QTLxGB interactions.

关键词： Obstructive sleep apnea   Claudin-4   IL-22   Intestinal repair  

摘要： Background Obstructive sleep apnea (OSA) is characterized as a low-grade inflammatory condition resulting from injury induced by intermittent hypoxia (IH). Interleukin-22 (IL-22), a mucosa-targeting cytokine, regulates tight junction proteins like Claudin-4 (CLDN4) to enhance barrier function, yet its role in OSA remains underexplored. Methods This pilot observational study included consecutive patients who underwent polysomnography. Plasma IL-22 and CLDN4 levels were measured using an enzyme-linked immunosorbent assay. Rat models of IH-exposed colon tissues were used for histology and immunohistochemical analysis. All statistical analyses were performed using SPSS 20.0. Results The expression of plasma IL-22 and CLDN4 was found to be positively correlated in OSA patients (r = 0.512, p  < 0.001). Plasma IL-22 and CLDN4 levels exhibited a significant positive correlation with the apnea–hypopnea index (both p  < 0.001), arousal index ( p  = 0.001 and p  = 0.014), oxygen desaturation index ( p  < 0.001 and p  = 0.001), and T90 (r = 0.379, p  < 0.001 and p  = 0.002). They also exhibited significant negative correlations with sleep efficiency (0.029; p  = 0.004), REM sleep phases ( p  = 0.037 and p  = 0.015), and mean oxygen saturation (SpO 2 ) ( p  = 0.044 and p  = 0.006). Plasma IL-22 and CLDN4 were significantly increased in the OSA group ( p  < 0.001), especially in severe OSA. The diagnostic value of plasma IL-22 combined with CLDN4 was superior to that of other indicators, with an AUC of 0.849 (0.783–0.915) for diagnosing OSA and an AUC of 0.909 (0.856–0.961) for diagnosing severe OSA. Pathological staining of the rat colon confirmed the damage of intermittent hypoxia (IH) to the intestine. The rat IH group had more IL-22 in the intestinal lymph node and more CLDN4 in the intestinal epithelium than the normal control (NC) group. The expression trends of IL-22 and CLDN4 in rat plasma were consistent with those observed in tissue samples. Conclusion Plasma IL-22 and

关键词： APP   antigen processing and presentation   bp   base pair   CDS   coding sequences   DRiPs   Defective ribosomal products   FDR   false discovery rate   HLA-1   Human Leucocyte Antigen class I   MS   mass spectrometry   MW   molecular weights   ORFs   open reading frames   PCPS   proteasome-catalyzed peptide splicing   RT   retention times   SPIsnake   Spliced Peptide Identification, Search space Navigation And K-mer filtering Engine  

摘要： Antigenic noncanonical epitope and novel protein discovery are research areas with therapeutical applications, predominantly done via mass spectrometry. The latter should rely on a well-characterized proteogenomic search space. Its size is barely known for antigenic noncanonical peptides and novel proteins, and this could impact their identification. To address these issues, we here develop an automated workflow comprised of Sequoia for the creation of RNA sequencing-informed and exhaustive sequence search spaces for various noncanonical peptide origins, and SPIsnake for pre-filtering and exploration of sequence search space before mass spectrometry searches. We apply our workflow to characterize the exact sizes of tryptic and nonspecific peptide sequence search spaces in a variety of definitions, their reduction when using RNA expression, their inflation by post-translational modifications, and the frequency of peptide sequence multimapping to different noncanonical origins. Furthermore, we explore the application of Sequoia and SPIsnake on HLA-I immunopeptidomes, thereby rescuing sensitivity in peptide identification when confronted with inflated search spaces. Taken together, Sequoia and SPIsnake pave the way for an educated development of methods addressing large-scale exhaustive proteogenomic discovery by exposing the consequences of database size inflation and ambiguity of peptide and protein sequence identification.

关键词： Allergy   bacteria   IgE   mast cell   activation   degranulation   LPS   infection   macrophage   priming   polarization   epigenetic   CCL   Chemokine C-C motif ligand   CXCL   C-X-C motif chemokine ligand   G-CSF   Granulocyte-colony stimulating factor   MHCII   Major histocompatibility complex II   EGR2   Early growth response protein 2   HLA   Human leukocyte antigen   MFI   Mean fluorescence intensity   ATAC-Seq   Assay for transposase-accessible chromatin using sequencing   BM   Bone marrow   BMCMC   BM-derived cultured mast cell   BMDM   BM-derived macrophage   CFU   Colony-forming units   DEG   Differentially expressed gene   DNP   2,4-Dinitrophenol   FCS   Fetal calf serum   FITC   Fluorescein isothiocyanate   GM-CSF   Granulocyte-macrophage colony-stimulating factor   HSA   Human serum albumin   iNOS   Inducible nitric oxide synthase   LB   Lysogeny broth   LPS   Lipopolysaccharide   M-CSF   Macrophage-colony stimulating factor   MoMPh   Monocyte-derived macrophage   PBCMC   Peripheral blood–derived cultured mast cell   PGD   2   Prostaglandin D   2   PGE   2   Prostaglandin E   2   RNA-Seq   RNA sequencing   TLR   Toll-like receptor  

摘要： Background Mast cells and macrophages are tissue-resident immune cells frequently found in close proximity in barrier organs. Macrophages show high plasticity and microenvironmental factors, such as cytokines, can influence their phenotype. Mast cells are central in allergic reactions where allergens cause mast cell activation via antigen-specific IgE antibodies and the release of a multitude of inflammatory substances. While macrophages have clearly defined physiologic roles in tissue maintenance and host defense against microbes, biological mast cell functions are less well defined. Objective In the current study, we aimed to understand the interplay of mast cells and macrophages and how mast cell–released mediators can shape macrophage phenotype and function. Methods Using primary in vitro models of mast cells and macrophages combined with microscopic, functional, metabolic, genetic, and epigenetic analyses, we investigate the macrophage polarization effects of mast cell mediators produced on activation with IgE and antigen. We apply a macrophage engraftment strategy to explore potential in vivo implications of mast cell–mediated priming. Results We find that preformed and newly synthesized mediators released by activated mast cells shape a macrophage phenotype different from the classical M1/M2 macrophage paradigm. Exposure to supernatant of activated mast cells induces epigenetic reprogramming of macrophages. This profound priming effect strongly alters macrophage phagocytosis, cytokine production, and transcriptomic responses on secondary exposure to bacteria or their products. Importantly, in vivo transfer of primed macrophages also significantly affects the outcome of sterile inflammation and bacterial peritonitis. Conclusion Our study highlights the great potential of activated mast cells as directors of macrophage function.

关键词： CD44   CYFRA 21-1   Diagnostic   IL-8   OSCC   POCT   Salivary biomarkers  

摘要： Objective: Early diagnosis of oral squamous cell carcinoma (OSCC) is a global concern, particularly in lowresource environments where invasive diagnostics limit population-wide screening. The purpose of this review is to evaluate the potential of salivary biomarkers: Interleukin-8 (IL-8), Cytokeratin 19 fragment (CYFRA 21-1), and Cluster of Differentiation 44 (CD44) in OSCC diagnosis. Methods: A methodical search was conducted across PubMed, Embase, Scopus, and Web of Science databases till December 2024. Following PRISMA guidlines, studies quantifying salivary IL-8, CYFRA 21-1, and CD44 levels in OSCC patients and healthy controls were included. Using a bivariate random-effects model, we retrieved and combined sensitivity, specificity, and area under the summary receiver operating characteristic (SROC) curve. The QUADAS-2 tool was used to evaluate risk of bias. A standardized mean difference (SMD) meta-analysis was also performed to assess quantitative elevation in biomarker levels between cases and controls. Results: Out of 311 articles reviewed, 20 eligible studies were included. IL-8, CYFRA 21-1, and CD44, individually, each biomarker demonstrated good diagnostic accuracy (with pooled AUCs of 0.88, 0.90, and 0.91, respectively), with CD44 showing overall highest diagnostic consistency. The combined biomarker panel exhibited significantly enhanced diagnostic precision (pooled AUC: 0.92;sensitivity: 88 %;specificity: 90 %). This combined metric was derived using a bivariate meta-analysis model applied to studies that evaluated at least two or more of the three biomarkers together. These findings were supported by corresponding forest plots and SROC curves, demonstrating low publication bias and moderate heterogeneity. Consistency across sample size, geographic origin, and assay technique were verified by subgroup analyses. Conclusion: Salivary IL-8, CYFRA 21-1, and CD44 taken together provide a scientifically strong, non-invasive method for OSCC diagnosis on a uni

关键词： 干细胞   卵巢颗粒细胞   衰老   机制   氧化应激   抑制凋亡   细胞因子   抗氧化   抗炎症反应  

摘要： 背景:干细胞疗法作为一种新兴的治疗手段,有望改善卵巢环境,延缓卵巢颗粒细胞的衰老,为高龄妊娠女性带来新的希望。目的:综述干细胞抗卵巢颗粒细胞衰老的机制及研究进展。方法:检索中国知网和PubMed数据库中关于干细胞抗卵巢颗粒细胞衰老的文献,以“干细胞,卵巢颗粒细胞,衰老”为中文检索词,以“stem cells,ovary granulosa cells,aging”为英文检索词,最终纳入67篇文献进行分析。结果与结论:①总结了5种卵巢颗粒细胞衰老的机制:DNA损伤和修复能力下降、氧化应激、线粒体功能受损、炎症反应、激素水平变化;②整理了当前干细胞治疗卵巢颗粒细胞衰老的5种机制:促进增殖和抑制凋亡、分化潜能及再生能力、分泌因子、抗氧化、抗炎症反应和免疫调节;③目前有多种类型的干细胞可通过多种方式协同治疗卵巢颗粒细胞衰老,干细胞疗法在恢复女性生育能力方面具有广阔前景。

关键词： 视网膜分支静脉阻塞   黄斑水肿   复发   细胞因子   血管内皮生长因子(VEGF)  

摘要： 目的:研究视网膜分支静脉阻塞继发黄斑水肿(BRVO-ME)抗血管内皮生长因子(VEGF)治疗后复发的相关危险因素。方法:选取2021年2月至2022年6月在山东第二医科大学附属医院眼科就诊的BRVO-ME患者32例32眼,采取3+PRN的抗VEGF治疗方案,随访时间6 mo。连续3次抗VEGF治疗后,根据治疗后6 mo OCT的黄斑中心凹厚度(CMT)变化,分为无复发组和复发组,应用悬浮液相检测法检测房水中多种细胞因子含量,比较两组间一般资料、CMT及细胞因子含量的变化,分析其与BRVO-ME抗VEGF治疗后复发的相关性。结果:无复发组19眼ME消退,复发组13眼ME复发或者未完全消退。与基线值相比,无复发组和复发组CMT在术后1 d,1、6 mo均有所改善(均P<0.05)。与无复发组相比,复发组在基线,术后1 d,6 mo的CMT值更大(均P<0.05)。复发组房水基线VEGF、单核细胞趋化蛋白-1(MCP-1)含量均显著高于无复发组(均P<0.05)。Spearman相关性分析显示,基线CMT与IL-1β、IL-5、IL-12、MCP-1及IP-10呈中度正相关(均P<0.05)。多因素逻辑回归分析显示,基线CMT、基线房水MCP-1含量均是ME复发的危险因素(OR>1,P<0.05)。结论:基线CMT和房水MCP-1水平是BRVO-ME患者抗VEGF治疗后复发的危险因素,基线CMT较高和基线房水MCP-1表达水平高的患者抗VEGF治疗后更容易复发。

关键词： Graft versus host disease   Graft versus leukemia   Major histocompatibility complex   Missing ligands   NK cell  

摘要： Background Natural killer (NK) cells express killer immunoglobulin-like receptors (KIRs), which regulate their functions. Self-human leukocyte antigens (HLA) class I molecules act as inhibitory molecules for KIRs, blocking the killing activity of NK cells. Since normal NK activity may affect the outcomes of hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) from their HLA-matched sibling donors, we investigated the interaction between KIRs and class I HLA presented on NK cells. Complications such as graft-versus-host disease (GvHD) or transplant rejection may result because of deficient expression of class I HLA ligand inhibitors in the transplant recipient. Methods We examined the effect of missing KIR ligands (MSL) and KIR haplotypes on GvHD development, relapses, death, infections, and cell recovery in HSCT patients. Our group included 59 patients [ n  = 24 with acute myeloid leukemia (AML), n  = 12 with chronic myeloid leukemia (CML), n = 12 with myelodysplastic syndrome (MDS), and n  = 11 with acute lymphoblastic leukemia (ALL)], who received HSCT/BMT from their sibling donors. Results Our results showed that haplotype AA was more common than Bx in donors for patients with MDS and was associated with a higher incidence of chronic (c) GvHD ( p  = 0.003). In this group, we also observed a statistically significant relationship between the AA donor haplotype and absolute neutrophil count reconstruction of 0.5 G/l (0.5 × 10 9 cells/L) under 28 days ( p  = 0.03). Our results also showed an excellent correlation between KIR MSL values and cGvHD in AML patients ( r  = 0.9932). Conclusion Our results indicate that KIR/HLA class I analysis at the stage of selection of a related donor could have an impact on the results of hematological transplantation and possibly reduce complications.