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关键词： 糖尿病肾病   血液透析   感染   白介素-10   单核细胞趋化蛋白-1   相关性  

摘要： 目的探讨血清白介素-10(IL-10)、单核细胞趋化蛋白-1(MCP-1)与糖尿病肾病(DN)维持性血液透析患者感染的相关性。方法回顾性分析,采集2021年1月至2024年6月濮阳市人民医院收治的182例DN行维持性血液透析患者资料,所有患者入院时接受主要血清学指标检测,重点记录血清IL-10、MCP-1水平。根据患者透析治疗期间有无发生感染纳入感染组、未感染组,比较两组血清IL-10、MCP-1水平,一般资料及实验室指标差异,重点分析血清IL-10、MCP-1与DN患者维持性血液透析期间合并感染的关系。结果182例DN行维持性血液透析患者并发感染51例,感染率为28.02%。限制性立方样条分析结果显示,血清IL-10、MCP-1连续变化与DN维持性血液透析患者发生感染的关联强度呈非线性剂量反应关系(P<0.05);经χ^(2)检验Phi系数相关性检验,结果显示,DN维持性血液透析患者发生感染风险与血清IL-10、MCP-1水平呈正相关关系(Phi=0.502、0.631,P<0.05)。结论血清IL-10、MCP-1连续变化与DN维持性血液透析患者发生感染有显著的非线性关联强度,二者水平均与患者并发感染呈正相关关系。

关键词： Chronic rhinosinusitis   Nasal polyps   Phase 3   Biologics   Type 2 inflammation   ACQ   Asthma Control Questionnaire   CI   Confidence interval   CRSwNP   Chronic rhinosinusitis with nasal polyps   CT   Computed tomography   ESS   Endoscopic sinus surgery   FeNO   Fractional exhaled nitric oxide   FEV1   Forced expiratory volume in 1 second   IgE   Immunoglogulin E   IL   Interleukin   LMS   Lund-Mackay score   LOS   Loss of smell score   MCID   Minimal clinically important difference   NCS   Nasal congestion score   NPS   Nasal polyp score   QoL   Quality of life   SNOT22   22-item Sinonasal Outcome Score   TSLP   Thymic stromal lymphopoietin   T2I   Type 2 inflammation  

摘要： Chronic rhinosinusitis with nasal polyps (CRSwNP) is commonly associated with type 2 inflammation and may be punctuated by exacerbations requiring systemic corticosteroids and eventually a need for surgery. The use of biologics to target type 2 inflammation has greatly ameliorated the management of refractory CRSwNP. Currently available biologics act upstream by blocking the epithelial cytokine thymic stromal lymphopoietin (TSLP) or downstream blocking type 2 cytokines including Interleukin (IL4), IL5, and IL13, or Immunoglogulin E (IgE). Synthesizing the data from phase 3 randomized control trials using Forest plots to compare crude 95% confidence intervals permits an indirect comparison of different biologics in terms of their relative efficacy. Anti-TSLP (tezepelumab) or anti-IL4Rα (dupilumab) provide the best improvements in coprimary end points of nasal polyp and congestion score compared with other biologics including anti-IL5/5Rα (mepolizumab, depemokimab, and benralizumab) and anti-IgE (omalizumab). Greater improvements were also seen with tezepelumab and dupilumab in regard to olfaction as loss of smell score and University of Pennsylvania Smell Identification Test, computerized tomography sinus imaging as Lund Mackay score, and also the need for surgery or rescue use of systemic corticosteroid. Prospective pragmatic studies are required to directly compare different biologics in type 2 high and low CRSwNP, including effects on the unified airway in patients with severe asthma and CRSwNP, in particular to look at quality of life as well as clinical remission for upper and lower airway outcomes.

关键词： MLKL   mixed lineage kinase domain-like protein   P-MLKL   phosphorylated MLKL   ICU   Intensive Care Units   MODS   multiple organ dysfunction syndrome   PIPs   phosphatidylinositol phosphates   Nec-1   Necrostatin-1   TLR   Toll-like receptors   DAMPs   damage-associated molecular patterns   NETs   Neutrophil extracellular traps   TNFR   tumor necrosis factor receptor   TNFR1   tumor necrosis factor receptor 1   TNF-α   tumor necrosis factor-α   IFN-γ   Interferon gamma   P2A   proteinphosphatase2A   PRRs   Pattern recognition receptor   IL-1β   Interleukin-1β   IL-18   Interleukin-18   GPX4   Glutathione peroxidase 4   ROS   reactive oxygen species   RNS   reactive nitrogen species   PS   phosphatidylserine   ELISA   Enzyme-linked immunosorbent assay   ScRNA-seq   single-cell RNA sequencing   APCs   antigen-presenting cells   PAMPs   Pathogen-associated molecular patterns   HMGB1   high mobility group box 1   TRADD   TNF-associated death domain   TNF   Tumor Necrosis Factor   RIPK1   receptor-interacting protein kinases 1   RIPK3   receptor-interacting protein kinases 3   CIAP1/2   cellular inhibitor of apoptosis 1 /2   DISC   death-inducing signaling complex   NF-κB   nuclear factor-κB   ZBP1   Z-DNA binding protein 1   FADD   Fas associated via death domain   RIPK3   receptor interacting protein kinases 3   TLRs   Toll-Like Receptors   TLR3   Toll-like receptor 3   TLR4   Toll-like receptor 4   TRIF   TIR domain-containing adapter-inducing interferon-β   NETs   neutrophil extracellular traps   LPS   lipopolysaccharides   SCFAs   short-chain fatty acids   GALT   gut-associated lymphoid tissue   NLRP3   NOD-like receptor protein 3   CASP1/3/6/7/8   caspase 1/3/6/7/8   MTOR   mammalian target of rapamycin   ROS   reactive oxygen species   SIRS   systemic inflammatory response syndrome   MSCs   mesenchymal stem cells   AI   artificial intelligence   NK   natural killer   Necroptosis   Sepsis   PANoptosis   Gut microbiota  

摘要： Sepsis, a life-threatening condition characterized by systemic inflammatory responses, remains a significant challenge in clinical settings due to its complex pathogenesis and limited therapeutic strategies. Central to this conundrum is the role of cell death mechanisms, particularly necroptosis, in the progression and resolution of sepsis. Necroptosis, a regulated form of necrotic cell death, not only exacerbates inflammation through the release of intracellular contents but also compromises barrier functions, facilitating microbial translocation and systemic spread. While current therapeutic approaches predominantly focus on broad-spectrum antibiotics and supportive care, they often overlook the intricate interplay of cell death pathways and the host immune response. This review aims to shed light on the mechanistic intricacies of necroptosis in sepsis and its potential as a promising therapeutic target. By understanding and modulating necroptosis, we may unlock innovative strategies that address the current shortcomings in sepsis treatment and pave the way for a new era of targeted therapies.

关键词： 喉咽清颗粒   风热证   急性咽炎   便秘   免疫球蛋白  

摘要： 目的探讨喉咽清颗粒对风热证急性咽炎伴便秘成人患者的疗效及免疫球蛋白指标的影响。方法选取2023年1月至2024年4月上海电力医院收治的风热证急性咽炎伴便秘成人患者98例,按随机数字表法分为对照组(常规西医治疗)和观察组(在对照组基础上应用喉咽清颗粒),各49例。比较两组患者临床疗效、中医证候积分、慢性便秘严重度评分量表(CCS)评分,血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、C-反应蛋白(CRP)、免疫球蛋白-A(IgA)、免疫球蛋白E(IgE)及唾液分泌型免疫球蛋白-A(SIgA)水平。结果观察组治疗总有效率较对照组高(P<0.05)。两组治疗前中医证候积分、CCS评分,血清TNF-α、IL-6、CRP、IgA、IgE及唾液SIgA水平无统计学差异(P>0.05);观察组治疗后中医证候积分、CCS评分,血清TNF-α、IL-6、CRP、IgE水平低于对照组(P<0.05),血清IgA及唾液SIgA水平高于对照组(P<0.05)。结论喉咽清颗粒对风热证急性咽炎伴便秘成人患者疗效显著,能缓解临床症状,减少炎症因子分泌,改善免疫球蛋白指标。

关键词： 急性肺炎   Sema7a   巨噬细胞   蛋白质组学   细胞因子  

摘要： 目的探究Sema7a促进急性肺炎炎症消退的分子机制。方法本研究采用Sema7a-eKO基因敲除小鼠模型、HE染色、ELISA检测及蛋白质组学分析等新技术在分子、组织及动物三个水平上,探明了游离Sema7a在调节急性肺炎小鼠模型中巨噬细胞代谢重编程,促进巨噬细胞向M2分化,加速炎症消退及促进肺组织恢复稳态中的作用。结果Sema7a-/-及Sema7a+/+肺炎小鼠模型显示在24、48、72和96 h时两组小鼠肺泡结构均有不同程度的破坏。与Sema7a+/+小鼠相比,Sema7a-/-小鼠肺组织浸润更多的中性粒细胞及红细胞,肺泡结构破坏更明显,且表现出更强的中性粒细胞浸润及更长的消退间隔(26.2 h vs.13.8 h,P<0.05);ELISA分析显示在第48 h时,Sema7a-/-小鼠肺泡灌洗液中IL-6、KC、TNF-α和IL-1β显著高于Sema7a+/+对照组小鼠(P均<0.05);我们通过5D Label-free蛋白质组学技术明确了Sema7a处理后MΦs中101320个肽段和7357个蛋白质的变化,GO二级功能注释分析显示巨噬细胞生物进程有59个蛋白质分子的变化与其细胞变化过程相关,52个蛋白质分子的变化与生物学功能的调节相关,37个蛋白质分子的变化与其代谢过程相关(P均<0.05);KEGG通路注释和富集分析显示线粒体呼吸链信号通路变化显著,Sema7a刺激后MΦs表面的M1标记物(STAT-1,CD40,CD80)和炎症细胞因子显著降低,而M2标记物(Arg1、CD163和CD20)和IL-10在蛋白水平显著增加。结论游离Sema7a蛋白可通过调节急性肺炎模型中巨噬细胞代谢重编程增强其氧化磷酸化水平,促进巨噬细胞向M2型细胞分化,进而促进肺部炎症消退,最终使肺组织恢复稳态。

关键词： 原发性高胆固醇血症   混合型高脂血症   前蛋白转化酶枯草溶菌素9抑制剂  

摘要： 目前,前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂作为一类新兴的药物,在原发性高胆固醇和混合型高脂血症疾病临床实践中占据了一席之地。《2022 ACC专家共识决策路径:非他汀类药物降低低密度脂蛋白胆固醇(LDL-C)在动脉粥样硬化性心血管疾病风险管理中的作用》根据心血管结局试验现有结局数据和安全性特征,推荐将PCSK9单克隆抗体作为PCSK9抑制剂首选治疗药物。该共识进一步肯定PCSK9单克隆抗体的治疗地位,明确推荐其作为部分心血管病一级预防和二级预防人群的联合治疗首选药物。

关键词： 重症肺炎   成人   支气管肺泡灌洗术   临床症状   血清指标  

摘要： 目的评估支气管肺泡灌洗术对成人重症肺炎疗效以及对血清可溶性细胞间黏附分子-1(sICAM-1)和白细胞介素-6(IL-6)水平的影响。方法共纳入安康市中医医院2020年1月至2023年12月收治的102例成人重症肺炎患者,采用随机分层抽样法将患者分为对照组和研究组。对照组男28例,女23例;年龄45~70(58.24±6.53)岁;体重指数(24.56±3.21)kg/m2;病程7~20(12.48±3.67)d。研究组男27例,女24例;年龄46~69(57.92±6.28)岁;体重指数(24.78±3.15)kg/m2;病程8~19(12.35±3.54)d。对照组接受盐酸氨溴索注射液治疗,15 mg盐酸氨溴索与50 ml 5%葡萄糖注射液混合后静脉滴注,滴注时间约30 min,每日两次;研究组在此基础上联合电子支气管镜支气管肺泡灌洗术治疗,每周1~2次,两组均治疗14 d。比较两组患者临床症状(咳嗽、咳痰、发热)消失时间,血清指标(sICAM-1、IL-6)、呼吸力学指标[气道阻力(RAW)、肺动态顺应性(Cdyn)、呼吸做功量(WOB)]、临床肺部感染评分(CPIS)、急性生理功能和慢性健康状况评分系统Ⅱ(APACHEⅡ)评分和不良反应(恶心、皮肤瘙痒、气道出血、气道痉挛、腹泻)发生情况。统计学方法采用t检验、χ^(2)检验。结果研究组咳嗽、发热、咳痰消失时间为(2.22±1.11)d、(1.46±0.38)d、(2.41±0.34)d,短于对照组(6.45±1.06)d、(2.51±0.57)d、(5.77±0.82)d,差异均有统计学意义(t=19.682、10.946、27.031,均P<0.05)。治疗14 d后,研究组的sICAM-1和IL-6水平为(134.51±28.17)µg/L、(17.41±1.53)µg/L,低于对照组(168.25±35.44)µg/L、(23.20±1.86)µg/L,差异均有统计学意义(t=5.322、17.168,均P<0.05);研究组的RAW和WOB为(9.71±2.15)cmH_(2)O/(L·s)(1 cmH_(2)O=0.098 kPa)、(0.53±0.09)J/L,低于对照组(11.87±2.68)cmH_(2)O/(L·s)、(0.65±0.14)J/L,Cdyn为(36.84±4.99)ml/cmH_(2)O,高于对照组(32.63±4.85)ml/cmH_(2)O,差异均有统计学意义(t=4.490、5.149、4.321,均P<0.05);研究组的CPIS和APACHEⅡ评分为(3.41±0.83)分、(11.65±2.74)分,低于对照组(4.76±1.21)分、(14.55±3.19)分,差异均有统计学意义(t=6.570、4.925,均P<0.05)。研究组的不良反应发生率为3.92%(2/51),低于对照组的13.73%(7/51),但差异无统计学意义(χ^(2)=3.047,P=0.081)。结论支气管肺泡灌洗术能有效改善成人重症肺炎患者的临床症状,降低sICAM-1和IL-6水平,改善呼吸力学指标,并降低CPIS和APACHEⅡ评分,显示出较高的安全性和耐受性。

关键词： MHC-associated peptides   immunopeptidomics   phosphorylation   post-translational modification   cancer immunotherapy   β2m   β-2-microglobulin protein   APBA   amino phenylboronic acid   APC   antigen-presenting cell   CAD   collision-activated dissociation   ETD   electron transfer dissociation   HCD   higher energy collisional dissociation   HILIC   hydrophilic interaction chromatography   HLA   human leukocyte antigen   IDA   iminodiacetic acid   MHC   major histocompatibility complex   nCE   normalized collision energy   NTA   nitrilotriacetic acid   PBMC   peripheral blood mononuclear cell   PC   precolumn   PHEA   polyhydroxyethyl aspartamide   PTM   post-translational modification   STAGE   stop and go extraction   TCR   T-cell receptor  

摘要： Over the past 3 decades, the Hunt laboratory has developed advancements in mass spectrometry–based technologies to enable the identification of peptides bound to major histocompatibility complex (MHC) molecules. The MHC class I processing pathway is responsible for presenting these peptides to circulating cytotoxic T cells, allowing them to recognize and eliminate malignant cells, many of which have aberrant signaling. Professor Hunt hypothesized that due to the dysregulation in phosphorylation in cancer that abnormal phosphopeptides could be presented by this pathway, and went on to demonstrate that this was, in fact, the case. Thereafter, the laboratory continued to sequence MHC-associated phosphopeptides and contributed several improved methods for their enrichment, detection, and sequencing. This article summarizes the most recent advancements in identification of modified MHC-associated peptides and includes the cumulative list of phosphopeptides sequenced by the Hunt lab. Further, many other post-translational modifications (PTMs) were found to modify MHC peptides, including O-GlcNAcylation, methylation, and kynurenine; in total, we present here a list of 2450 MHC-associated PTM peptides. Many of these were disease-specific and found across several patients, thus highlighting their potential as cancer immunotherapy targets. We are sharing this list with the field in hopes that it might be used in investigating this potential. Overall, the Hunt lab’s contributions have significantly advanced our understanding of antigen presentation and dysregulation of PTMs, supporting modern immunotherapy and vaccine development efforts.

关键词： 结肠炎,溃疡性   槐角丸   糖皮质激素类   炎性细胞因子   肠道屏障功能  

摘要： 目的研究槐角丸联合糖皮质激素在溃疡性结肠炎临床治疗中的效果。方法选择2020年9月至2024年9月,于我院就诊的溃疡性结肠炎患者共计80例,依据随机原则将其划分为2个组。对照组单用糖皮质激素,观察组联用槐角丸。比较2组的疗效、肠道屏障功能、炎性细胞因子[白细胞介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)、白细胞介素-33(IL-33)、转化生长因子-β1(TGF-β1)]。结果治疗4周后,观察组的有效率高于对照组(P<0.05);治疗4周后,观察组肠道屏障功能优于对照组(P<0.05);治疗4周后,观察组肠道黏膜愈合情况优于对照组(P<0.05);治疗4周后,观察组炎性因子水平优于对照组(P<0.05);治疗期间,2组的不良反应比较差异无统计学意义(P>0.05)。结论联合应用槐角丸与糖皮质激素可能提高溃疡性结肠炎患者的临床疗效,改善患者炎症指标及肠道屏障功能,并未增加不良反应的发生风险。

关键词： 哮喘-慢性阻塞性肺病重叠症   风咳方   沙美特罗替卡松   外泌体   高迁移率族蛋白1   趋化因子配体13  

摘要： 目的:探讨风咳方联合沙美特罗替卡松治疗稳定期哮喘-慢阻肺重叠征(ACO)的临床疗效,以及对血清外泌体miR-34a和细胞因子表达的影响。方法:随机纳入ACO患者188例,根据随机数字表法分为对照组和观察组各94例,对照组采用沙美特罗替卡松吸入治疗,观察组联合应用自拟风咳方,疗程均为2周。比较两组中医证候积分,肺功能[FEV1%预计值、FEV1/FVC、最大呼气中段流量(MMEF)和呼气峰流速(PEF)],炎症介质[hs-CRP、中性粒细胞与淋巴细胞比值(NLR)、白细胞介素-6(IL-6)],细胞因子[高迁移率族蛋白1(HMGB1)和趋化因子配体13(CXCL13)],以及外泌体miR-34a表达量。评估临床疗效。结果:两组治疗后中医证候积分、HMGB1、CXCL13、hs-CRP、NLR、IL-6和miR-34a表达量较治疗前降低,且观察组明显低于对照组(均P<0.05);两组治疗后FEV1%预计值、FEV1/FVC、MMEF和PEF较治疗前升高,且观察组明显高于对照组(均P<0.05)。观察组总有效率显著高于对照组(P<0.05)。结论:风咳方联合沙美特罗替卡松治疗稳定期ACO可以进一步提高临床疗效,改善肺功能,减轻炎症反应,抑制外泌体miR-34a表达。