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关键词： 血清   VEGF   FGF19   GDF15   IL-6   肝癌   预后评估  

摘要： 目的 分析血清血管内皮生长因子（vascular endothelial growth factor，VEGF）、成纤维细胞生长因子19（fibroblast growth factor 19，FGF19）、生长分化因子15（growth differentiation factor 15，GDF15）、白细胞介素6（interleukin-6，IL-6）评估肝癌预后的价值。方法 选择2021年1月—2024年8月淄博市博山区中医院收治的90例肝癌手术患者作为研究对象，术后随访12个月，68例未复发，设为未复发组；22例复发，设为复发组。对比两组患者血清VEGF、FGF19、GDF15、IL-6水平。制作ROC曲线分析血清VEGF、FGF19、GDF15、IL-6评估肝癌预后的价值。结果 术后，患者血清VEGF、FGF19、GDF15、IL-6水平低于术前，未复发组血清VEGF、FGF19、GDF15、IL-6水平低于复发组（P<0.05）。ROC曲线分析结果显示，血清VEGF、FGF19、GDF15、IL-6联合检测AUC为0.723，灵敏度为77.27%，特异度为60.29%（P=0.001）。结论 血清VEGF、FGF19、GDF15、IL-6可用于评估肝癌预后。

关键词： Ichthyophthirius multifiliis   Pelteobagrus vachelli   interleukin-1 beta   interleukin-6   serum amyloid A  

摘要： Interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and serum amyloid A (SAA) are key pro-inflammatory mediators in the regulation of immune responses. The hypothesis posits that their expression varies with the progression of Ichthyophthirius multifiliis (Ich) infection and may serve as predictors of disease outcome. To elucidate their spatiotemporal dynamics, the full-length CDS of IL-1 beta, IL-6, and SAA in Pelteobagrus vachelli were cloned, and then their mRNA levels were tracked from infection onset (day 0) to resolution (day 40) or mortality in seven tissues. Key findings revealed a surge in IL-1 beta expression in the kidney and SAA expression in the spleen at 5 days post-infection (dpi), coinciding with no visible symptoms. Significant SAA elevation in the head kidney was observed at 10 dpi, preceding the emergence of white spots on the skin. This was followed by gill-specific SAA downregulation at 20 dpi, when 40% of fish presented with white spots. Complete clinical resolution by 40 dpi correlated with reduced hepatic SAA and branchial IL-1 beta levels. Notably, the concurrent upregulation of all three mediators occurred exclusively in the skin of moribund individuals. These findings identify potential biomarkers for tracking host inflammatory responses in ichthyophthiriasis.

关键词： 急性胰腺炎   生长抑素   乌司他丁   肿瘤坏死因子   白介素-6  

摘要： 文章旨在对重症急性胰腺炎(SAP)患者实施乌司他丁+生长抑素治疗下改善血清[C反应蛋白(CRP)、白介素-6(IL-6)、血清肿瘤坏死因子-α(TNF-α)]水平的效果。方法 于2021年1月至2023年12月,选取SAP患者为研究对象,通过电脑随机分组,将患者分为接受生长抑素治疗的对照组(共54例)以及额外加入乌司他丁治疗的实验组(亦为54例),进而对比两组在用药方案上的病情改善成效。结果 研究发现,干预组的总体疗效显著优于参照组(96.30%对比85.19%),差异具有统计学意义,P值<0.05。参照组与干预组CRP、IL-6、TNF-α与血清淀粉酶(AMS)、内毒素(ET)水平治疗相比未见差异,P>0.05;干预组治疗后较参照组更低,P<0.05;两组急性生理及慢性健康状况评分系统(APACHEⅡ)评分在治疗相比未见差异,P>0.05;于治疗后对比参照组,干预组更低,P<0.05。结论 SAP患者经生长抑素+乌司他丁治疗,在改善血清指标的同时,缓解病情严重程度,值得被临床推广与应用。

关键词： 化痰安神方   HT22细胞   凋亡   NLRP3/IL-18/NF-κB信号通路   炎症小体  

摘要： 目的 基于核因子激活的B细胞的NOD-样受体热蛋白结构域相关蛋白3(NOD-like receptor pyrin domain-containing protein 3, NLRP3)/白细胞介素-18(interleukin-18, IL-18)/κ-轻链(nuclear factor-activated B cellκ-light chain, NF-κB)信号通路探讨化痰安神汤抑制神经元细胞凋亡的作用机制。方法 体外培养HT22小鼠海马神经元细胞,C57小鼠灌胃化痰安神方后制备含药小鼠血清,CCK-8法筛选化痰安神汤含药血清最佳干预浓度。采用不同浓度含药血清处理HT22细胞后,予脂多糖(lipopolysaccharide,LPS)诱导其发生凋亡,CCK-8法L-乳酸脱氢酶(L-lactate dehydrogenase,L-LDH)生化检测法和Annexin V/PI染色法用于检测细胞损伤与凋亡情况,Western blotting法、反转录聚合酶链式反应用于测定通路相关蛋白P-NF-κB/NF-κB、凋亡相关的斑点样蛋白(apoptosis-associated speck-like protein containing, ASC)、NLRP3、Caspase-1的表达,酶联免疫吸附测定法用于测定IL-18的表达。过表达NLRP3后重复试验,进行单基因功能验证。结果 化痰安神方含药血清可改善LPS诱导的细胞损伤和凋亡,降低细胞L-LDH浓度(P<0.05);显著下调NLRP3/IL-18/NF-κB信号通路相关蛋白的转录表达(P<0.05);显著降低细胞内IL-18浓度;同时过表达NLRP3可逆转化痰安神方含药血清对HT22细胞凋亡抑制作用(P<0.05)。结论 化痰安神方能够通过抑制NLRP3/IL-18/NF-κB信号通路改善神经元细胞凋亡。

关键词： Cyprinus carpio   Un-ionized ammonia   RT-qPCR   Pro-inflammatory cytokines   Stress response   Leptin  

摘要： BackgroundCommon carp is one of the most economically important freshwater fish species globally. Ammonia exposure, a frequent challenge in aquaculture, can lead to significant economic losses. This study investigated the impact of un-ionized ammonia (UIA) exposure on the expression profiles of three key genes in common carp fry: interleukin-1 beta (IL-1 beta), corticotropin-releasing hormone (CRH), and leptin a1 (Lep-a1). These genes are crucial indicators of immune response, stress regulation, and appetite control, respectively. Fish were exposed to 0.7 mg/L of UIA, and gene expression was analysed in liver and gill tissues at five time points (12 h, 2-, 4-, 7-, and 14-days of exposure) using quantitative real-time PCR (RT-qPCR).ResultsResults demonstrated that expression levels of all three genes were significantly affected by exposure time and tissue type. IL-1 beta, CRH, and Lep-a1 were upregulated in both liver and gill tissues, with the liver consistently showing higher expression levels. Notably, significant positive correlations were observed between each pair of the three genes studied, suggesting a coordinated physiological response to ammonia stress. The liver emerged as a key organ in orchestrating the long-term adaptive response, while the gills exhibited a more acute, transient *** study provides valuable insights into the molecular mechanisms underlying the physiological response of common carp to ammonia toxicity. The findings highlight the complex interplay between immune, stress, and metabolic pathways in coping with ammonia exposure. A deep understanding of these mechanisms could lead to improved management strategies in aquaculture and the development of potential biomarkers for assessing stress responses in fish populations.

关键词： 肾移植   肾功能延迟恢复   淋巴细胞   滤泡辅助性T细胞   血肌酐  

摘要： 目的 探讨外周血CD4+T淋巴细胞亚群与肾移植受者肾功能延迟恢复（DGF）及近期预后的相关性,以期帮助优化肾移植术前评估并为DGF免疫机制研究提供参考。方法 回顾性分析2022年6月—2023年10月于苏州大学附属第一医院进行肾移植的103例受者的临床资料。最终纳入61例受者,根据术后肾功能恢复情况分为DGF组（20例）和肾功能正常恢复（IGF）组（41例）。采用流式细胞术检测受者肾移植术后第7天外周血中各CD4+T淋巴细胞亚群的比例和绝对值,比较两组受者临床资料及外周血淋巴细胞亚群差异,针对存在差异的亚群,进一步分析在DGF组受者中,外周血Tfh及PD-1+Tfh细胞亚群比例和绝对值与术后第7天血肌酐（Scr）水平的相关性,绘制受试者工作特征（ROC）曲线并计算曲线下面积（AUC）,评估与术后第7天Scr水平相关性最强的CD4+T淋巴细胞亚群的比例及绝对值对近期肾功能的预测效能。结果 DGF组和IGF组的Th1、Th2、Th17和调节性T细胞（Treg）等细胞的比例和绝对值比较差异无统计学意义（P>0.05）;DGF组滤泡辅助性T细胞（Tfh）及PD-1+Tfh细胞的比例及绝对值均高于IGF组（P<0.000 1）。DGF组较IGF组术后1个月及1年的Scr水平更高（P<0.01）、估算肾小球滤过率（eGFR）更低（P<0.01,P=0.02）。Spearman相关性分析显示:Tfh及PD-1+Tfh细胞亚群比例和绝对值与术后第7天Scr水平呈正相关（P<0.05）。ROC曲线显示,PD-1+Tfh细胞比例预测受者术后1个月Scr、eGFR的AUC分别为0.73（95%CI:0.61～0.86）、0.75（95%CI:0.62～0.88）,预测术后1年Scr、eGFR的AUC分别为0.72 （95%CI:0.59～0.86）、0.70（95%CI:0.58～0.83）。结论 Tfh及PD-1+Tfh细胞比例及绝对值升高与肾移植受者术后DGF有关,PD-1+Tfh细胞比例可能有助于预测受者近期肾功能。

关键词： bile salt   demicellization   enthalpy   entropy   Gibbs free energy   IL   thermodynamics  

摘要： Isothermal titration calorimetric (ITC) study can probe critical micelle concentration (CMC) as well as the associated thermodynamics of surfactant aggregation. Micellization behavior of two bile salts, sodium cholate (NaC) and sodium deoxycholate (NaDC) were evaluated through ITC studies;subsequently the enthalpy change (Delta Hdemic0$$ {\Delta H}_{\mathrm{demic}}<^>0 $$), Gibbs free energy change (Delta Gdemic0$$ {\Delta G}_{\mathrm{demic}}<^>0 $$) and entropy change (Delta Sdemic0$$ {\Delta S}_{\mathrm{demic}}<^>0 $$) of demicellization processes were also evaluated in the presence of varied concentration of an ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) and at different temperatures at ascertain concentration of IL (1.0 mM). In order to distinguish the effect of IL from the corresponding common salt, studies were also carried out in aqueous sodium tetrafluoroborate (NaBF4) medium. CMC values decrease with increasing IL/NaBF4 concentration and increase with increasing temperature. CMC reduction in case of NaDC-NaBF4 system is more prominent, while considering temperature variation, the CMC rise in NaC-[bmim]BF4 system is more significant. Delta Hdemic0$$ {\Delta H}_{\mathrm{demic}}<^>0 $$ values considerably depend on temperature. Temperature rise causes an increase in Delta Gdemic0$$ {\Delta G}_{\mathrm{demic}}<^>0 $$ values. However, it decreases with increasing IL/NaBF4 concentration for both NaC and NaDC. Effect of temperature is less prominent on the Delta Gdemic0$$ {\Delta G}_{\mathrm{demic}}<^>0 $$ variation whereby the demicellization processes are found to be entropy driven processes. Temperature variation exhibits greater effect on Delta Hdemic0$$ {\Delta H}_{\mathrm{demic}}<^>0 $$ than the additive concentration. Such comprehensive studies hold promise for diverse scientific and industrial applications besides the fundamental understanding on IL induced micellization.

关键词： anti-IL-1 treatment   anakinra   canakinumab   child   neonate   CAPS   pregnancy   paternal-maternal exposure  

摘要： Objectives To determine the effect of paternal and maternal anti-IL-1 treatment exposures on pregnancies and neonatal outcomes in *** A single-centre study consecutive adult CAPS patients and their partners was performed between January 2012 and July 2024. All were screened for pregnancies and anti-IL-1 exposure before conception and/or during pregnancy;teratogenic co-therapies resulted in exclusion. Data included patient characteristics, disease activity, anti-IL-1 treatment, pregnancy complications, neonatal outcomes and child health *** Among 112 patients 11 pregnancies were recorded including eight maternal and three paternal anti-IL-1 exposures. All patients had moderate CAPS, 43% had hearing loss. At conception, all patients received canakinumab. Among the eight maternal exposures, six switched to anakinra, one refused the switch and continued canakinumab, and one had to be switched back to canakinumab due to significant local injection reactions. Pregnancy complications included one miscarriage and one preterm birth, both associated with disease activity. Neonatal outcomes were favorable, with a mean gestational age of 37 + 6 weeks and an average birth weight of 3028 g. No congenital malformations were observed. Neonatal complications included one presumed sepsis (culture negative) requiring IV antibiotics and one mild respiratory syncytial virus infection. CAPS was diagnosed in 5 of 11 offspring, all of whom achieved effective disease control early, with no cases of hearing loss or *** In summary, the benefit risk ratio of maternal and paternal anti-IL-1 exposure during conception and pregnancy in our CAPS patients was favourable. CAPS disease activity may have a significant impact on development of pregnancy complications.

摘要： High-dose posttransplantation cyclophosphamide (HD-PTCy), given at 50 mg/kg/day on days +3/+4, is a standard-of-care graft-versus-host disease (GVHD) prophylaxis for allogeneic hematopoietic cell transplantation (HCT). Our murine MHC-haploidentical HCT studies suggested intermediate-dose PTCy produces superior GVHD control compared with HD-PTCy and PTCy is maximally effective on day +4. We conducted a single-institutional prospective phase 1/2 trial to reduce PTCy dosing to 25 mg/kg/day on days +3/+4 or on day +4 only for myeloablative HLA-haploidentical bone marrow HCT using PTCy, sirolimus, and mycophenolate mofetil. Among 35 patients, 89% were ethnic/racial minorities, 46% had high/very-high-risk disease, and median comorbidity score was 3. The phase 1 dose-limiting-toxicity, grade III-IV acute GVHD, was not observed after either reduced-PTCy dose level. PTCy 25 mg/kg/day on days +3/+4 (intermediate-dose (ID)-PTCy;n = 23), the phase 2 dose, resulted in no grade II-IV acute GVHD;2-year cumulative incidences of chronic GVHD requiring systemic immunosuppression, nonrelapse mortality, and relapse were 13%, 17%, and 22%, and 2-year overall survival, disease-free survival, and GVHD-free/relapse-free survival were 61%, 61%, and 52%. In exploratory analysis compared with HD-PTCy (n = 5), ID-PTCy resulted in significantly faster engraftment and T-cell reconstitution, fewer transfusions, less mucositis, and reduced severity of BK-virus-associated cystitis/urethritis;area-under-the-curve exposure of 4-hydroxycyclophosphamide (4HCY), a key cyclophosphamide metabolite, correlated with these outcomes but not with chronic GVHD occurrence. Ideal-body-weight-based PTCy dosing best approximated 4HCY exposure. ID-PTCy is effective and has apparent clinical benefits compared with HD-PTCy. Before broader implementation, further studies are needed to confirm these findings and define optimal PTCy dosing across various donor/graft types. This trial was registered at ***.

关键词： C1q/TNF-related protein 1   chronic inflammation   kidney fibrosis   macrophage activation  

摘要： Chronic kidney disease (CKD), characterized by persistent inflammation and progressive renal fibrosis, remains a major therapeutic challenge due to incomplete understanding of its pathogenesis. Since C1q/TNF-related protein 1 (CTRP1) plays a potential role in fibrosis and inflammation in other tissues, we investigated the role of CTRP1 in patients and mice with CKD. Here CTRP1 expression was increased in plasma and decreased in kidneys from patients with CKD. Upregulation of renal CTRP1 with adeno-associated-CTRP1 were associated with decreased renal fibrosis, inflammation, macrophage accumulation and activation in mice models. Mechanistically, CTRP1 abolished the expression of TGFß1-induced macrophage M2-associated genes and the transcriptional regulators Yes-associated protein Yap)/transcriptional coactivator with PDZ-binding motif (Taz). Additionally, upregulation of CTRP1 could partly down regulate LPS-stimulated expression of pro inflammatory genes . Conditioned media from TGFß1-CTRP1-pretreated macrophages could less efficiently stimulate fibroblast activation compared to those from TGFß1-pretreated macrophages. Thus, our study reveals local CTRP1 as a potential regulator of chronic inflammation and kidney fibrosis through regulating macrophage activation. Taking together, these findings support renal CTRP1 as a novel therapeutic target for CKD.