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关键词： Platelet transfusion refractoriness   HLA-I antibodies   Compatible blood transfusion   Immune microsphere liquichip  

摘要： To investigate the differences in HLA-I antibody distribution and corresponding platelet transfusion effectiveness among patients with a history of platelet transfusion refractoriness(PTR) in the Han population of Zhejiang, China, to ensure the rational utilization of platelet resources.A retrospective analysis was conducted on 77 patients with a history of PTR admitted to the Hematology Department of Zhejiang Provincial Hospital of Traditional Chinese Medicine from May 2018 to December 2022. Testing was conducted for HLA-I antibodies in platelets were tested using an immune microsphere liquid chip. The distribution of antibodies and their intensities were analyzed along with the distribution characteristics of antibodies by disease type, sex, age, and blood type. Furthermore, the relationships between HLA-I antibody intensity distribution and transfusion frequency, as well as transfusion outcomes, were *** average positive rates of HLA-A, -B, and -C antibodies were 0.393, 0.527, and 0.242. The number of weakly positive and total positive HLA-I antibodies in the ITP group was significantly lower than in the other disease categories (P < 0.05).Positive HLA-I antibody count was not related to the patient's sex, blood type, or age. In contrast, positive HLA-I antibody count was significantly higher for platelet transfusions > 10 than for platelet transfusions <= 10. As anticipated, the effectiveness of HLA standard antigen-matched platelet transfusions was significantly superior to random platelet transfusions (P < 0.001).The distribution of HLA-I antibodies in PTR patients among the Han Chinese population in Zhejiang, China is relatively extensive. An increase in the frequency of platelet transfusions leads to higher frequency and stronger intensity of HLA-I antibody production, resulting in poorer transfusion outcomes. HLA standard antigen-matched platelet transfusions can effectively address the occurrence of PTR.

关键词： intervertebral disc   degeneration   back pain   link N   interleukin-1 beta   inflammation  

摘要： Intervertebral disc (IVD) disease is typically characterized by the degradation of IVD tissue, secretion of inflammatory and painful factors, and hyperinnervation of the disc. The pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) has been regarded as a principal factor in orchestrating disc degeneration. Link N (LN) is a peptide derived from the link protein that has been shown to promote extracellular disc regeneration even in an inflammatory milieu;however, no mechanism(s) has been described for their behaviour to date. Building on prior studies on LN, we hypothesize that LN directly inhibits IL-1 beta. IVD degeneration was experimentally induced in New Zealand white rabbits, followed by the injection of either sLN or saline as the vehicle control. To determine the expression of markers of pain, histology was performed. Cultured human Nucleus Pulposus disc cells (hNP) were used to determine the effects of LN on IL-1 beta-induced changes in gene expression, including the effects on IL-1 beta, TNF alpha, and IL6 signalling. Isolated murine dorsal root ganglia (DRG) neurons were used to assess the effect of LN on IL-1 beta-induced neuronal hyperactivity. LN significantly reduced IL-1 beta-induced NF-kappa B activation in a dose-dependent manner in disc cells and was further able to modulate IL-1 beta-induced gene expression, inflammatory mediators, and neurotrophic factors. Peptide docking simulations revealed that LN could interact with IL-1 beta. A direct interaction of LN and IL-1 beta was revealed through co-immunoprecipitation experiments. Although IL-1 beta was able to hypersensitize DRG neurons following a seven-day exposure, as demonstrated by Ca2+ imaging, this effect was significantly blunted when co-treated with LN. LN demonstrates a novel mechanism of action by directly inhibiting IL-1 beta, in addition to mitigating IL-1 beta-induced hypersensitivity in DRG neurons. These data suggest a potential role for LN in reducing discogenic pain.

关键词： Gastric cancer   Prognostic nutrition index   LAG3   MHC class II  

摘要： BackgroundThe prognostic nutrition index (PNI) has recently been highlighted as a predictor of immune checkpoint (IC) inhibitor efficacy in gastric cancer (GC). Although LAG3, an IC molecule, has gained considerable attention, its association with PNI remains *** and methodsWe retrospectively analyzed clinical data from 796 GC patients who underwent radical gastrectomy to identify which previously reported nutritional index had the greatest impact on prognosis. Single-cell RNA sequencing was performed on 38 GC tissues, and multiplex immunofluorescence staining was conducted on 59 GC tissues to evaluate the relationship between nutritional indices and IC molecule expression in cytotoxic CD8-positive T *** low preoperative PNI was identified as the strongest predictor of poor prognosis among the nutritional indices in GC patients. The expression of not only PDCD1 (encoding PD1) but also LAG3 in cytotoxic CD8-positive T cells was significantly higher in GC with low PNI compared to those with high PNI. Among cytotoxic CD8-positive T cells, the proportion of LAG3-positive cells was greater than that of PDCD1-positive cells, particularly in GC with low PNI, and most LAG3-positive cells did not co-express PDCD1. Additionally, the expression of MHC class II, a ligand for LAG3, was higher in GC cells with high levels of epithelial-mesenchymal transition-related molecules in GC with low PNI compared to those with high *** can reflect LAG3 expression in cytotoxic CD8-positive T cells and MHC class II expression in GC cells.

关键词： Zika virus   Placenta   Trophoblast   First trimester pregnancy   Interferon   Interferon lambda   Interferon stimulated genes  

摘要： BackgroundZika virus (ZIKV) is a positive-strand RNA virus of the Flaviviridae family. Maternal ZIKV infection during pregnancy can spread to the placenta and fetus causing severe neurological defects and infants born with microcephaly. Here, we investigated ZIKV infection and the cellular innate antiviral immune response in first trimester human placental explant cultures and isolated primary villus cytotrophoblasts (CTBs).MethodsPlacentas were obtained with informed consent from women undergoing elective pregnancy termination and either cultured as placental explants or used to isolate primary CTBs. Explants and CTBs were both infected with ZIKV (PRVABC59), and samples evaluated for infection by qRT-PCR, viral plaque and ELISA assays, and immunohistochemical or immunocytochemical *** demonstrate robust infection and production of ZIKV in placental explant and CTB cultures. Both displayed delayed upregulation of interferons (IFN), most notably IFN beta and IFN lambda 2/3, and a panel of interferon stimulated genes (ISG) (IFI6, IFIT1, IFIT2, IFITM1, ISG15, MX1, RSAD). Stimulation of explants and CTBs with the dsRNA mimic poly(I: C), caused immediate IFN and ISG upregulation, demonstrating the first trimester placenta is innate immune competent. This suggests that either ZIKV blocks the early innate response, or the placental response is inherently *** these data show that first trimester placenta is susceptible to ZIKV infection which induces a delayed type III IFN antiviral response. This delay likely creates an environment favourable to ZIKV replication and dissemination across the early gestation placenta to fetal tissue, causing pathologies associated with congenital ZIKV syndrome.

关键词： Renal cell carcinoma   JUN/AP-1   IL-17 pathway   Gut microbial metabolites   Icaritin   Molecular docking  

摘要： The gut microbiome plays a crucial role in renal diseases, influencing conditions such as renal cell carcinoma (RCC), acute kidney injuries, and diabetic nephropathy. Recent studies highlight the association between gut microbial metabolites (GMM) and RCC progression. This study employs a computational network pharmacology framework to explore the mechanistic action of gut microbiota-derived metabolites against RCC. GMM were selected from the gutMgene database and analyzed for common targets using DisGeNET, Gene Card, and OMIM. Downstream analysis included gene ontology, KEGG pathway enrichment, metabolite-target-pathway-disease network construction, and protein-protein interaction analysis. Further, key metabolites were evaluated for drug-likeness, ADMET properties, and molecular docking, followed by molecular dynamics simulations (MDS) to assess complex stability. The JUN/AP-1 gene emerged as the prime target, exhibiting the highest binding affinity with Icaritin (- 5.9 kcal/mol), followed by Quercetin and Luteolin. MDS confirmed the stable binding of Icaritin to the active site throughout the simulation. These GMM may influence anticancer activity through distinct regulatory pathways involving the JUN/AP-1 gene, either by inhibiting or modulating its function. These insights establish a basis for further in vitro and in vivo investigations, supporting the development of microbiome-based therapeutic *** abstractThe graphical abstract illustrates a computational network pharmacology and computer-aided analysis approach to investigating gut microbiota-derived metabolites in renal cell carcinoma (RCC). It highlights core target genes, gene ontology, KEGG pathways, and network analyses. The right section depicts gut microbiota, specifically Bacterium sp. MRG-PMF-1 produces Icaritin, which inhibits the JUN gene, potentially suppressing RCC progression. Molecular docking and molecular dynamics simulations confirm stable binding interactions, supporting

关键词： 吴茱萸碱(EVO)   免疫抑制剂   细胞周期   细胞因子   流式细胞术  

摘要： 目的 探究吴茱萸碱（EVO）对活化T细胞增殖的抑制特性。方法 采用密度梯度离心法从健康供体中提取外周血单个核细胞（PBMC），采用免疫磁珠法纯化T细胞，抗人CD3/CD28抗体活化T细胞。以不同浓度的EVO（0.37、1.11、3.33、10）μmol/L作用于T细胞。流式细胞术测定T细胞增殖率、凋亡率、存活率、CD25表达水平以及细胞周期分布。ELISA分析细胞因子白细胞介素2（IL-2）、IL-17A、IL-4和IL-10的表达水平。结果 EVO（1.11、3.33、10）μmol/L能有效抑制活化T细胞增殖，其半数抑制浓度IC50为（1.5±0.3）μmol/L。EVO不诱导活化T细胞凋亡，且不影响静息T细胞的存活率。EVO不影响活化T细胞CD25的表达及IL-2的分泌。EVO阻滞T细胞周期于G2/M期，使G2/M期细胞增加，且具有浓度-效应关系。EVO不影响活化T细胞分泌IL-4、IL-10，但显著抑制IL-17A的分泌。结论 EVO对T细胞的活化过程无显著影响 ， 但可通过阻滞细胞周期于G2/M期 ， 从而抑制T细胞的增殖 ， 并显著抑制促炎因子IL-17A的分泌。提示EVO有望作为先导物 ， 促进低毒高效性免疫抑制剂的研发 ， 并有助于阐释传统中药吴茱萸在抗炎及免疫调节中的作用机制。

关键词： 恒温扩增-实时荧光法   呼吸道多病原检测   抗原法  

摘要： 呼吸道多病原检测中分别使用抗原法和恒温扩增-实时荧光法,对比两种检测方法应用效果。方法 观察患者选择我院诊断的呼吸道多病原检测120例,观察开始于2024年9月,观察结束于2025年1月,并且根据患者采取的检测方法不同分成荧光法组与抗原法组,方法均以传统的核酸定量荧光法(qPCR)为金标准,荧光法组使用恒温扩增-实时荧光法检测,抗原法组使用抗原法检测,对比两组应用效果。结果 (1)荧光法组和抗原法组操作时间、操作满意度情况:荧光法组操作时间高于抗原法组操作时间,荧光法组操作满意度高于抗原法组操作满意度,(t=3.785,p=0.032)。(2)荧光法组和抗原法组检测阳性率情况:荧光法组检测阳性率高于抗原法组检测阳性率,(x2=14.904,p=0.008)。(3)荧光法组和抗原法组诊断效能情况:荧光法组特异性高于抗原法组特异性;荧光法组灵敏度高于抗原法组灵敏度,荧光法组准确率高于抗原法组准确率,(x2=13.271,p=0.009)。结论 呼吸道多病原检测中使用恒温扩增-实时荧光法检测效果优良,可推广。

摘要： Excessive alcohol consumption drives the development of alcohol-associated liver disease (ALD), including steatohepatitis, cirrhosis, and hepatocellular carcinoma, and its associated complications, such as hepatorenal syndrome. Hepatocyte death, inflammation, and impaired liver regeneration are key processes implicated in the pathogenesis and progression of ALD. Despite extensive research, therapeutic options for ALD remain limited. Interleukin-22 (IL-22) has emerged as a promising therapeutic target due to its hepatoprotective properties mediated through the activation of signal transducer and activator of transcription 3 (STAT3) signaling pathway. IL-22 enhances hepatocyte survival by mitigating apoptosis, oxidative stress, and inflammation while simultaneously promoting liver regeneration through the proliferation of hepatocytes and hepatic progenitor cells and the upregulation of growth factors. Additionally, IL-22 exerts protective effects on epithelial cells in various organs affected by ALD and its associated complications. Studies from preclinical models and early-phase clinical trials of IL-22 agonists, such as F-652 and UTTR1147A, have shown favorable safety profiles, good tolerability, and encouraging efficacy in reducing liver injury and promoting regeneration. However, the heterogeneity and multifactorial nature of ALD present ongoing challenges. Further research is needed to optimize IL-22-based therapies and clarify their roles within a comprehensive approach to ALD management. This review summarizes the current understanding of IL-22 biology and its role in ALD pathophysiology and ALD-associated complications along with therapeutic application of IL-22, potential benefits and limitations.

关键词： MC-LR   Apoptosis   TNF-R1   RIPK1   HEK293  

摘要： In recent years, the outbreak of cyanobacterial blooms has become increasingly frequent. Microcystin-LR (MC-LR), a metabolite of cyanobacteria, poses a significant threat to the ecosystem and human health. Several studies have demonstrated that MC-LR might induce renal cell apoptosis, as a consequence of tissue damage. However, the molecular mechanisms underlying MC-LR-initiated renal injury remain to be determined. This investigation aimed to determine the role of apoptosis in MC-LR-induced kidney damage and its potential underlying mechanisms using the human embryonic kidney (HEK293) cell line. The results of TUNEL and immunofluorescence assays indicated that MC-LR induced increased apoptosis in HEK293 cells. Compared to control, the mRNA expression levels of RIPK1, caspase-8, and TNF-alpha were elevated following incubation with MC-LR, while the mRNA expression level of Bcl-2/Bax was decreased. The protein levels of RIPK1, TNF-R1, and caspase-8 were elevated in the MC-LR-treated HEK293 cells. Data demonstrated that MC-LR induced renal cell apoptosis through activation of the TNF-R1/RIPK1 pathway, providing new insights into understanding the toxic mechanisms attributed to MC-LR.

关键词： 银屑病   白细胞介素-17A抑制剂   头皮   真菌   内源转录间隔区测序  

摘要： 目的 探究白细胞介素-17A(interleukin-17A,IL-17A)抑制剂治疗前后银屑病患者头皮皮损,及其与正常人群头皮表面真菌菌群结构的差异,为开发新型治疗或辅助方案提供支持.方法 纳入2024年1-9月海南省第五人民医院17例初次使用IL-17A抑制剂治疗的头皮银屑病患者,分别采集治疗前(M0)、治疗4周(M4)、治疗12周(M12)以及10例同年龄段健康人群对照,观察患者使用IL-17A抑制剂治疗后的治疗效果及皮损改善情况.收集受试者皮损处头皮样本,采用内源转录间隔区(internal transcribed space,ITS)扩增子测序技术以及illumina nextseq 2000测序平台,经过DNA提取、PCR扩增、文库构建、上机测序等步骤获得原始测序数据.对测序数据进行注释,并进行生物信息学、医学统计学分析.结果 17例患者经IL-17A抑制剂治疗12周后,完全缓解病例数2例,显著缓解病例数13例,部分缓解病例数2例,总有效率100.00%.IL-17A抑制剂治疗后,各组间真菌群落的α多样性分析差异无统计学意义(P>0.05).β多样性分析提示随着治疗的进展,银屑病患者头皮真菌微生态情况得到改善.组间差异性物种分析,经过生物制剂治疗后,在属水平上,马拉色菌(Malasseziales)的相对丰度减少,弯孢菌(Curvularia)、浅孔菌(Grammothele)、毛栓菌(Trametes)、短梗霉菌(Aureobasidium)的相对丰度增多,差异有统计学意义(P<0.05).结论 IL-17A抑制剂治疗寻常型银屑病疗效显著.寻常型银屑病头皮皮损的真菌微生态与健康人群存在一定差异,经IL-17A抑制剂治疗后趋于正常.