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关键词： 中医药   免疫球蛋白A肾病   辨证论治   免疫功能   研究进展  

摘要： 免疫球蛋白A肾病(IgAN)是一种常见的肾小球疾病,其特征是IgA在肾脏中的沉积,该病的临床表现多样,包括无症状的血尿、蛋白尿,部分患者可发展至严重的肾功能衰竭。中医药在治疗IgAN方面具有丰富的经验,其强调辨证施治,即根据患者的具体病情、体质和症状,制订个性化的治疗方案,旨在通过调整人体的阴阳平衡,改善肾脏功能,减少炎症损伤,从而达到治疗疾病的目的。因此,现对中医药治疗IgAN的最新研究进展进行综述,为临床实践提供参考。

关键词： 5FU   5-Fluorouracil   IL10   Interleukin 10   FA   Fatty acid   ABC transporters   ATP-binding cassette transporters   Colon cancer   CCL20   IL10   Fatty Acid   Chemoresistance  

摘要： Conventional chemotherapeutics for colon cancer often fail to achieve optimal clinical outcomes, as many patients develop resistance and experience significant toxicity, thereby increasing the overall health burden. Understanding the mechanisms conferring resilience to cancer cells is essential for developing more effective therapies. 5-Flourouracil (5FU) is the standard of care used for colon cancer. 5FU-associated inflammation, characterized by a change in cytokine profile, enables the colon cancer cells to evade cell death, thereby undermining the cytotoxic effects of the drug. Current study underscores the significance of CCL20 signaling, which is linked to inflammatory conditions and is elevated during colon carcinogenesis, in tempering the cytotoxic effects of 5FU. The presented data demonstrate an inverse correlation between CCL20 concentrations in colon cancer and sensitivity to 5FU. Moreover, treatment with 5FU further stimulates CCL20 signaling in colon cancer cells, likely via increased fatty acid efflux. Notably, the findings reveal that IL10 signaling is under negative regulation of CCL20. Additionally, exposure to 5FU elevates IL10 levels, thus creating a complex interplay of pro-inflammatory and anti-inflammatory pathways. Such dual activation of contrasting mechanisms undermines the therapeutic efficacy of 5FU. Therefore, the insights gained from this study emphasize the significance of addressing immune signatures characterized by CCL20 and IL10 to enhance the effectiveness of 5FU in colon cancer treatment.

关键词： urticarial vasculitis   urticarial vasculitis syndrome   urticarial vasculitis treatment   anti-TNF   anti-tumor necrosis factor   HUV   hypocomplementemic urticarial vasculitis   IgE   immunoglobulin E   IL   interleukin   UV   urticarial vasculitis  

摘要： Background Urticarial vasculitis (UV) is a rare form of small vessel vasculitis, and there are limited published data on its management. Objective This study aims to review the current therapeutic options for UV. Methods A PubMed search was conducted, selecting articles published from 2000 to January 2024. Results Of 305 identified articles, 21 were included. Mild cutaneous UV can be treated with antihistamines and nonsteroidal anti-inflammatory drugs. For intermittent cutaneous UV, short courses of systemic corticosteroids are recommended. Hydroxychloroquine, colchicine, and dapsone show comparable efficacy to corticosteroids and are often used for refractory and hypocomplementemic UV patients. In cases with persistent symptoms, first-line immunosuppressants such as azathioprine, cyclophosphamide, cyclosporine A, methotrexate, and mycophenolate mofetil may be considered. Some studies suggest the effectiveness of omalizumab, rituximab, canakinumab, anakinra, and plasmapheresis. Limitations Only noninterventional observational studies, which were mostly retrospective, were found and included in our scoping review. Furthermore, the study is limited by small sample sizes due to the nature of UV. Conclusion UV is a rare condition with insufficient treatment data. This scoping review outlines potential treatment options, highlighting the need for further research.

关键词： hUC-MSCs   NINJ1   IFN-γ   TNF-α   Sepsis  

摘要： Purpose:To investigate the regulatory role of nerve injury-induced protein 1(NINJ1)in the anti-inflammatory function of human umbilical cord mesenchymal stem cells(hUC-MSCs)co-stimulated by interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α).Methods:hUC-MSCs were expanded in vitro using standard protocols,with stem cell characteristics confirmed by flow cytometry and multilineage differentiation *** immunomodulatory properties and cellular activity of cytokine-co-pretreated hUC-MSCs were systematically evaluated via quantitative reverse transcription RT-qPCR,lymphocyte proliferation suppression assays,and Cell Counting Kit-8 viability *** sequencing,Western blotting and small interfering RNA interference were integrated to analyze the regulatory mechanisms of NINJ1 *** roles of NINJ1 in pretreated hUC-MSCs were elucidated through gene silencing combined with lactate dehydrogenase release assays,Annexin V/Propidium Iodide apoptosis analysis,macrophage co-culture models,and cytokine Enzyme-Linked Immunosorbent *** efficacy was validated in a cecal ligation and puncture-induced septic mouse model:80 mice were randomly allocated into 4 experimental groups(n=20/group):sham group(laparotomy without cecal ligation);phosphate-buffered salinetreated group(cecal ligation and puncture(CLP)+0.1 mL phosphate-buffered saline);hUC-MSCs(small interfering RNA(siRNA)-interferon-gamma and tumor necrosis factor-alpha co-stimulation(IT))-treated group(CLP+hUC-MSCs transfected with scrambled siRNA);and hUC-MSCs(siNINJ1-IT)-treated group(CLP+hUC-MSCs with NINJ1-targeting siRNA).Results:hUC-MSCs demonstrated compliance with International Society for Cellular Therapy criteria,confirming their stem cell ***-γ/TNF-αco-pretreatment enhanced the immunosuppressive capacity of hUC-MSCs,accompanied by the reduction of cellular viability,while concurrently upregulating pro-inflammatory cytokines such as interleukin-6 and inte

关键词： 25(OH)D   IL-6   cytokine   inflammation   pregnancy   vitamin D  

摘要： Background Non-Hispanic Black women have a 1.5 times greater rate of preterm birth (PTB, any birth occurring at <37 wk of gestation) than non-Hispanic White women. Black women are also more likely to have vitamin D deficiency (VDD; 25[OH]D <20 ng/mL) than White women. Vitamin D has anti-inflammatory effects, which may help explain the association of VDD with PTB in Black women. Objectives To examine associations between inflammatory biomarkers and VDD with PTB as an outcome. Methods We used an exploratory retrospective cross-sectional design utilizing data collected as part of the larger Biosocial Impact on Black Births (BIBB) study. A case-control subsample was selected from the BIBB participants who had stored blood plasma available at 8–25 wk of gestation ( n = 172). Fifty-nine PTB cases were included in the current study, with a set of matched controls based on maternal age controls at a 1:2 ratio of PTB to term birth ( n = 113, 65.6%). Total 25(OH)D and cytokine levels were measured in the plasma. Results Seventy percent of women with PTB had VDD compared with 50% of women with term birth who had VDD. Other inflammatory biomarkers were not associated with PTB except for IL-6. The PTB group had higher IL-6 and lower 25(OH)D levels compared with term birth. In adjusted models controlling for IL-6 and other covariates, odds ratios (OR) for VDD remained significant for predicting PTB (OR: 2.45; 95% confidence interval: 1.18, 5.06; P = 0.016). Conclusions Increased VDD was associated with increased risk of PTB among Black women after controlling for IL-6 and other factors. Achieving adequate vitamin D status in early pregnancy may have an important role in PTB prevention as it is a significant predictor of risk after inflammation and other factors are considered. Further investigation is warranted.

关键词： HLA   immunopeptidomics   pancreatic cancer   ZenoSWATH DIA   cancer antigens   CTA   Cancer-Testis Antigen   DDA   Data-Dependent Acquisition   DIA   Data-Independent Acquisition   HLA   Human Leukocyte Antigen   HPH-RP   High pH Reversed-Phase Fractionation   LC-MS/MS   Liquid Chromatography-Tandem Mass Spectrometry   MS   Mass Spectrometry   PDAC   Pancreatic Ductal Adenocarcinoma   TAA   Tumor-Associated Antigen   vwZSW   Variable-Window ZenoSWATH   XIC   Extracted Ion Chromatogram   ZenoSWATH-MS   Zenotrap-enabled Sequential Window Acquisition of All Theoretical Mass Spectra  

摘要： Pancreatic ductal adenocarcinoma (PDAC), with its devastating prognosis and limited treatment options, demands innovative therapeutic strategies. T-cell-based immunotherapy has shown promise for many cancers, including PDAC, but is limited by our knowledge of the breadth of cancer-specific T-cell epitopes available. Thus, a comprehensive assessment of the immunopeptidome of PDAC is essential to pave the way for the effective design of immunotherapy and related interventions. In this study, we immunoaffinity purified Human Leukocyte Antigen (HLA) class I-bound peptides from the Panc1 cell line grown in the absence and presence of cytokine stimulation. These peptides were subjected to an off-line high-pH reversed-phase (HPH-RP) fractionation prior to data acquisition. We demonstrate that HPH-RP fractionation followed by data-dependent acquisition (DDA) is a relatively simple and reliable technique that expands the depth of coverage of the PDAC immunopeptidome, allowing the identification of over 22,500 canonical HLA-bound peptides. In addition, the complementary separation by HPH-RP improved the identification confidence, particularly in the case of co-fragmenting precursors in data-independent acquisition (DIA) workflows. This strategy facilitated the identification of a high number of cancer-testis antigen (CTA)-derived immunopeptides. However, given that fractionation is typically associated with an adsorptive loss, it is impractical to apply HPH-RP on often minuscule clinical specimens and biopsies. Thus, we explored the feasibility of immunopeptidome analysis with cellular inputs as low as 1 million cells (equivalent to approximately 1 mg of tissue) using either a ZenoSWATH DIA interpreted using a spectral library derived from the HPH-RP strategy, or an optimized DDA workflow on the SCIEX ZenoToF 7600 system. Both approaches enabled robust detection of CTA-derived and other potentially clinically actionable immunopeptides even at the lowest cellular inputs. We di

关键词： 兔抗人胸腺细胞免疫球蛋白   肾移植   诱导治疗   心脏死亡器官捐献   急性排斥反应   移植物功能延迟恢复   不良反应  

摘要： 目的 评估兔抗人胸腺细胞免疫球蛋白（rATG）诱导治疗在中国心脏死亡器官捐献肾移植受者中的疗效和安全性。方法 这是一项在中国进行的前瞻性、多中心、单臂、干预性研究（NCT03099122）。纳入接受心脏死亡器官捐献肾移植并接受rATG诱导治疗（累积剂量为5 mg/kg）的成年患者，采用单因素和多因素逻辑回归分析探讨与急性排斥反应（AR）、移植物功能延迟恢复（DGF）、移植物失功和患者死亡相关的因素。分析不良事件的发生情况。结果 共115例成年患者纳入研究，其中107例患者可评估疗效。活组织检查证实的AR(BPAR)和AR的发生率分别为2.8%(95%可信区间0.6%～8.0%)和4.7%(95%可信区间1.5%～10.6%)。DGF的发生率为13.1%(95%可信区间7.3%～21.0%)，移植物和患者生存率分别为97.2%(95%可信区间92.0%～99.4%)和99.1%(95%可信区间94.9%～100%)。多因素逻辑回归分析结果显示，供者血清肌酐和受者群体反应性抗体是DGF的危险因素（均为P<0.05）。常见的治疗期间出现的不良事件（发生率>5%）包括贫血（8.7%）、感染性肺炎（8.7%）和尿路感染（8.7%）。结论 标准剂量的rATG诱导治疗在中国心脏死亡器官捐献肾移植受者中表现出较低的BPAR、AR和DGF发生率，且耐受性良好。

摘要： Objectives The study objective was to determine if a common single nucleotide polymorphism in the interleukin 6 (IL-6) receptor (rs2228145, ***358Ala) predicted treatment response to tocilizumab in giant cell arteritis (GCA). Methods Genetic sequencing of the rs2228145 locus was performed in 2 independent cohorts of patients with GCA. Peripheral blood mononuclear cells (PBMCs) from patients and controls were evaluated for expression of the interleukin 6 receptor (IL-6R) and its coreceptor, gp130, using flow cytometry. The same PBMCs were stimulated with IL-6 and evaluated for downstream targets of IL-6: STAT3 phosphorylation (pSTAT3) and IL-17A expression. Results In total, 100 patients with GCA were included (derivation cohort n = 58; validation cohort n = 42). The rs2228145 variant predicted tocilizumab response in each cohort. In the derivation cohort, a gene dose-dependent response was observed with a 36% response rate in the homozygous patients and 95% response rate in patients without the variant ( P = .003). In the validation cohort, tocilizumab response rates were 50% for homozygotes and 85% for patients without the variant ( P = .04). pSTAT3 levels were significantly increased in response to IL-6 stimulation in a gene dose-dependent manner in CD4 T cells from patients with GCA but not controls. CD4 T cells from patients with GCA had significantly higher membrane expression of gp130 than healthy controls, and response to IL-6 correlated with gp130 expression. IL-17 producing CD4 T cells were increased in a gene dose-dependent response to IL-6 ( P < .01). Conclusions The rs2228145 variant is associated with decreased treatment response to tocilizumab and worse outcomes in GCA by enhancing CD4 T cell response to IL-6.

关键词： 血小板计数   纤维蛋白原   中性粒细胞/淋巴细胞比值   恶性肿瘤   肿瘤分期   相关性  

摘要： 目的探讨恶性肿瘤患者血小板计数(PLT)、纤维蛋白原(FIB)及中性粒细胞/淋巴细胞比值(NLR)与肿瘤分期的关系。方法收集134例恶性肿瘤患者的临床资料,依据TNM分期情况分为Ⅰ~Ⅱ期组(n=69)和Ⅲ~Ⅳ期组(n=65)。比较不同肿瘤分期恶性肿瘤患者的PLT、FIB、NLR水平;采用Spearman相关性检验分析PLT、FIB、NLR水平与肿瘤分期的相关性;绘制受试者工作特征(ROC)曲线,以曲线下面积(AUC)评价PLT、FIB、NLR对肿瘤分期的诊断效能。结果Ⅲ~Ⅳ期组恶性肿瘤患者PLT、FIB、NLR水平均明显高于Ⅰ~Ⅱ期组,差异均有统计学意义(P<0.01)。Spearman相关性检验结果显示,PLT、FIB、NLR水平与恶性肿瘤患者TNM分期均呈正相关(P<0.01)。ROC曲线显示,PLT、FIB、NLR诊断恶性肿瘤患者TNM分期的AUC分别为0.727、0.756、0.791。结论PLT、FIB、NLR水平与恶性肿瘤患者凝血纤溶系统异常及生理病理状态密切相关,这些指标可作为诊断肿瘤分期的生物学标志物。

关键词： Vialinin A   肝癌   耐药   HepG2/ADM细胞   TNF-α/TRAF6/NF-κB信号通路  

摘要： 目的探究Vialinin A对肝癌耐药细胞HepG2/ADM生长的抑制作用。方法CCK-8法筛选Vialinin A干预浓度,同时检测阿霉素、5-氟尿嘧啶、顺铂、长春新碱的抑制作用。将HepG2/ADM细胞分为对照组和Vialinin A 20、30、40μmol/L组,CCK-8法检测细胞活力,流式细胞术检测细胞凋亡率和细胞周期,RT-qPCR法检测细胞BCRP、MDR1、MRP1 mRNA表达,Western blot法检测细胞BCRP、MDR1、MRP1、TNF-α、TRAF6、TAK1、NF-κB p65、cleaved-Caspase-3蛋白表达。同时验证TNF-α对Vialinin A的逆转作用。结果Vialinin A可以抑制HepG2/ADM细胞增殖活力,IC50值为(31.52±2.76)μmol/L。与对照组比较,Vialinin A 20、30、40μmol/L组HepG2/ADM细胞凋亡率升高(P<0.01),细胞周期阻滞在G_(2)/M期,BCRP、MDR1、MRP1 mRNA和蛋白表达降低(P<0.05,P<0.01);Vialinin A 30、40μmol/L组细胞TNF-α、TRAF6、TAK1、NF-κB p65蛋白表达降低(P<0.01),cleaved-Caspase-3蛋白表达升高(P<0.01),并呈浓度依赖性。使用10 ng/mL TNF-α处理细胞48 h后可以有效逆转30μmol/L Vialinin A的作用。结论Vialinin A对HepG2/ADM细胞生长的抑制作用可能与抑制耐药基因表达和TNF-α/TRAF6/NF-κB信号通路有关。