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关键词： 脑组织   出血   白介素-10   神经发生   神经功能   修复  

摘要： 目的探讨白介素-10(IL-10)对脑出血雄性小鼠神经功能的影响及其可能作用机制。方法应用Ⅶ型胶原酶注射法制备脑出血(ICH)模型,于造模后第1、3、7、14、21、28 d分别进行神经功能缺失评分和感觉运动功能检测。于造模后第3、7、14 d取脑组织,采用免疫荧光法测定神经干细胞增殖和分化标记物的表达情况。结果与野生型(WT)组比较,IL-10基因敲除(KO)组在ICH术后第7、14、21 d的神经功能缺失评分较高(P<0.05);转角实验和前肢踏空实验显示,ICH术后第7、14 d KO组向右转向频次和踏空失误率高于WT组(P<0.05);前肢悬挂实验显示,ICH术后第7、14 d KO组悬挂时间低于WT组(P<0.05)。免疫荧光染色实验显示,ICH术后KO组的EDU、Ki67阳性细胞明显少于WT组(P<0.001);ICH术后KO组的NeuN/EDU双标阳性细胞、GFAP/EDU双标阳性细胞少于WT组(P<0.001)。结论IL-10对脑出血雄性小鼠神经功能存在影响;IL-10缺乏可能通过抑制脑内神经干细胞的神经发生,延缓脑出血后所致感觉和运动功能损伤的修复。

关键词： Hypoxia   Tibetan people   Monocytes   Medical hypoxia   Analysis of variance   Viral transmission and infection   COVID 19   SARS CoV 2  

摘要： We previously reported that Tibetan-specific variant of prolyl-hydroxylase-2 (PHD2)^D4E;C127S protects highlanders from hypoxia-triggered pathologies by destabilizing hypoxia-inducible factor (HIF)-1α. Others have reported that stabilized HIF1α negatively regulates interferon (IFN)-regulating factor (IRF)-3 under hypoxia. We examined the role of PHD2^D4E;C127S variant in IFN synthesis in immune cells during viral infections. Primary monocytes and cells engineered to express the PHD2^D4E;C127S variant displayed protection against dengue virus (DENV)-2 infection by suppressing HIF1α, in turn promoting IRF-3 and IFNα/β synthesis in hypoxia (3% O₂) in vitro. However, under normoxia (21% O₂), these mutant cells increased reactive oxygen species (ROS) generation following DENV2 infection. Increased ROS then suppressed PHD2^D4E;C127S activity, reflected by reduced hydroxylation and concomitant stabilization of HIF1α, resulting in suppressed IFN synthesis and higher DENV2 replication. The PHD2^WT cells demonstrated the opposite trend. Our data further confirmed the inverse correlation between HIF1α and IFN pathways. CAY10585, an HIF1α-inhibitor, decreased the DENV2 infection by increasing IFN-A/B and IRF-3/7/9 expression. HIF1α-depleted monocytes also showed a similar response to the infection. We extended our findings to COVID-19 infection. The CD4/CD8 T-cells collected from Tibetans with PHD2^D4E;C127S variant and exposed to SARS-CoV-2 infection showed elevated expression of IFN-γ in response to exposure to SARS-CoV-2 receptor-binding domain (RBD) peptide under hypoxia, and a lesser expression under normoxia. The study thus highlights a unique crosstalk of PHD2^D4E;C127S variant with HIF1α-IFN axis under environmental pO₂ in protecting or predisposing Tibetans to viral infections. This is an open access article, free of all copyright, and may be freely reproduced distrib

关键词： 非典型溶血尿毒综合征   基因分析   补体  

摘要： 回顾性分析2022年2月至2024年6月青岛大学附属医院肾病科的5例原发性非典型溶血尿毒综合征(aHUS)患者的临床特征、肾脏病理、基因检测及治疗情况。患者发病年龄14~29岁,男性2例,女性3例,4例患者存在前驱感染症状。5例患者起病时血清肌酐168.5~1230.2μmol/L,均表现为血尿、蛋白尿、高血压、非免疫性溶血性贫血、血小板减少、乳酸脱氢酶升高,外周血破碎红细胞范围0.5%~6.0%,血清结合珠蛋白低于正常值。4例患者血清补体C3下降,1例患者C3始终正常。1例患者血清H因子降低;1例血清抗H因子抗体阳性。4例患者接受肾穿刺活检,3例电镜下可见肾小球内皮细胞肿胀、内皮下间隙增宽的典型aHUS急性期病理特点,1例患者肾小球毛细血管呈缺血皱缩性改变,1例患者合并膜性肾病。5例患者均接受aHUS相关全外显子组高通量测序分析,全部存在基因杂合突变,其中补体相关基因突变常见,杂合突变为主。共发现8个基因变异,皆不在已知的aHUS致病基因库中。4例患者有机会应用依库珠单抗治疗,但因从初诊到应用的时间节点不同,呈现了不同结局。抗H因子抗体阳性患者应用利妥昔单抗治疗;合并膜性肾病的患者在依库珠单抗治疗半年后开始结合使用利妥昔单抗治疗。5例患者经治疗后血管内机械性溶血全部停止,乳酸脱氢酶和血小板恢复正常,肾功能得到不同程度的恢复。从致病本质入手,尽早及时应用补体C5抑制剂依库珠单抗可以使aHUS患者迅速获得临床缓解,降低终末期肾病的发生率,改善预后。

关键词： 西方蜜蜂   Smoothened(Smo)蛋白   多克隆抗体   免疫荧光   毛形感器  

摘要： Hedgehog(Hh)信号通路在多种生物的生长和发育过程中发挥重要作用,Smoothened(Smo)蛋白作为Hh信号通路的关键受体,是Hh信号转导的核心调控因子。为探究Smo蛋白在蜜蜂体内的功能及其调控机制,并深入解析蜜蜂嗅觉信号转导的分子机制,利用大肠杆菌BL21表达系统表达并纯化了Smo蛋白,并以纯化的Smo蛋白为抗原免疫新西兰白兔,制备了高活性和高特异性的Smo蛋白多克隆抗体。进一步采用免疫荧光技术检测了Smo蛋白在西方蜜蜂触角中的表达定位。结果显示,经大肠杆菌诱导表达后,重组Smo蛋白在83.72 ku处富集出明显目标条带,与预测的分子质量大小一致,表明诱导表达成功;SDS-PAGE分析结果显示,经富集纯化后,获得了高浓度的重组Smo蛋白洗脱液,表明Smo蛋白的纯化效果良好。ELISA检测结果显示,制备的Smo蛋白抗体效价达到1∶364500,表现出较高的免疫活性。免疫荧光结果显示,Smo蛋白在西方蜜蜂触角中广泛表达,尤其在毛形感器中高表达。研究成功制备了高纯度、高效价且特异性强的Smo蛋白多克隆抗体,并明确了Smo蛋白在西方蜜蜂触角中的表达定位。

关键词： asthma biologics   eosinophil   IL-5   severe asthma   type 2 inflammatio  

摘要： Background: Selecting optimal biologics based on type 2 biomarkers has been of interest in severe asthma treatment. However, few direct biomarker stratification-based comparisons have been made. Objective: To compare the effectiveness of anti-IL-5 (mepolizumab, benralizumab), omalizumab, and dupilumab ireducing the number of hospitalizations from asthma and exacerbations across all and eosinophil-stratified subgroups. Methods: A retrospective cohort study using the National Hospital Organization database (2016–2020) was performed. Asthmatic patients using biologics were selected, and the baseline backgrounds of the groups were balanced using inverse probability treatment weighting for propensity scores. Weighted rate ratios (RRs) were obtained using a Poisson regression model. Results: Among the 320 patients with asthma using biologics, 205 (64.1%), 75 (23.4%), and 40 (12.5%) were categorized into the anti-IL-5, omalizumab, and dupilumab groups, respectively. After weighting, there were 47.1, 30.0, and 62.6 hospitalizations per 100 person-years [omalizumab vs. anti-IL-5: weighted RR, 0.61 (0.34–1.08);dupilumab vs. anti-IL-5: 1.48 (0.81–2.72)], and 117.0, 134.6, and 287.3 exacerbations per 100 person-years [omalizumab vs. anti-IL-5: 1.13 (0.83–1.54);dupilumab vs. anti-IL-5: 2.69 (1.91–3.78)] in these respective groups. In patients with eosinophil of ≥ 300/μL, the dupilumab group had more exacerbations compared with the anti-IL-5 group [weighted RR, 2.85 (1.82–4.46)]. In patients with eosinophil of < 300/μL, the omalizumab group had fewer hospitalizations compared with the anti-IL-5 group [weighted RR, 0.32 (0.13–0.51)]. Conclusions: Anti-IL-5 biologics may be more effective than dupilumab in patients with high blood eosinophil countwhile less effective than omalizumab in patients with low eosinophil counts. © 2025, Allergy and Immunology Society of Thailand. All rights reserved.

关键词： 急性后循环脑梗死   年龄   NIHSS评分   中性粒细胞/淋巴细胞   临床加重   预测  

摘要： 目的探讨发病时年龄、入院时基线美国国立卫生研究院卒中量表(NIHSS)评分及中性粒细胞/淋巴细胞(NLR)对急性后循环脑梗死(APCCI)患者发病14 d内临床加重的预测价值。方法采用前瞻性队列研究,入选2023年9月至2024年5月首都医科大学附属北京友谊医院神经内科住院的APCCI患者作为研究对象。收集人口统计学资料、危险因素、入院时基线NIHSS评分、脑梗死病因等,计算NLR。终点事件为APCCI患者发病14 d内临床加重,评估标准为相对基线NIHSS评分增加≥2分。采用二分类Logistic回归分析评估影响APCCI患者发病14 d内临床加重的因素。采用Spearman相关性分析发病时年龄、入院时基线NIHSS评分及NLR与APCCI发病14 d内临床加重的相关性。采用受试者操作特征(ROC)曲线分析发病时年龄、入院时基线NIHSS评分和NLR对APCCI发病14 d内加重的预测效能。结果共纳入APCCI患者298例,其中发病14 d内临床加重者(加重组)78例,发病14 d内临床未加重者(未加重组)220例。加重组患者发病时年龄、入院时基线NIHSS评分、大动脉粥样硬化型脑梗死占比、中性粒细胞绝对值、入院当天随机血糖、NLR均高于未加重组,发病时血红蛋白、淋巴细胞绝对值均低于未加重组,差异均有统计学意义(P<0.05)。Logistic多元回归分析结果发现,发病时年龄(OR=1.06,95%CI:1.02~1.10)、入院时基线NIHSS评分(OR=1.87,95%CI:1.56~2.23)、NLR(OR=1.13,95%CI:1.03~1.23)与APCCI发病14 d内临床加重密切相关(P<0.05)。Spearman相关性分析结果显示,发病时年龄、入院时基线NIHSS评分及NLR与APCCI发病14 d内临床加重均呈正相关(r=0.210、0.222、0.210,P<0.05)。ROC曲线结果显示,发病时年龄、入院时基线NIHSS评分和NLR对APCCI发病14 d内临床加重具有较高的预测效能。结论发病时年龄、入院时基线NIHSS评分及NLR可作为对APCCI患者发病14 d内临床加重的预测因素。

关键词： Acupuncture Therapy   Point,Tianshu(ST25)   Point,Zusanli(ST36)   Colitis,Ulcerative   Inflammatory Bowel Disease   Gastrointestinal Microbiome   Interleukin-6   Rats  

摘要： Objective:To observe the effects of acupuncture on intestinal flora and inflammatory factor interleukin(IL)-6 in ulcerative colitis(UC)model rats and to explore the related mechanism of acupuncture in treating ***:Thirty-two Sprague-Dawley rats were randomly divided into a normal control(NC)group,a model(MO)group,a mesalazine(ME)group,and an acupuncture(AC)group,with 8 rats in each ***,except those in the NC group,were given a 2.5%sodium dextran sulfate solution to establish UC *** successful modeling,rats in the ME group were treated with mesalazine by gavage twice a day for 7 continuous days;rats in the AC group received acupuncture at bilateral Tianshu(ST25)and Zusanli(ST36)with needles retained for 20 min each time,once a day for 7 consecutive *** intervention,changes in the intestinal flora diversity,colon tissue damage degree,and inflammatory factor expression in each group of rats were ***:The body mass increased slowly in the MO group compared to the NC *** intervention,the body mass increased more significantly,colon injuries recovered,and intestinal flora diversity improved in the ME and AC groups compared to the MO group(P<0.05).The IL-6 expression level was higher in the MO group compared to the NC group(P<0.05).The IL-6 expression level decreased in the AC group compared to the MO group(P<0.05).Conclusion:Acupuncture at Tianshu(ST25)and Zusanli(ST36)improves body mass loss and colon injuries,regulates intestinal flora diversity,and reduces the expression of inflammatory factor IL-6 in the colon tissue of UC rats,therefore alleviating the disease severity of UC.

关键词： 鲍曼不动杆菌   荚膜多糖   血清型   临床预后   耐药表型  

摘要： 目的分析鲍曼不动杆菌(AB)各K抗原分型(KL)的耐药表型及感染患者临床预后情况。方法横断面研究。于2011—2021年从我国8个省份10家医院的血流感染(BSI,234例)、医院获得性肺炎(HAP,423例)、腹腔感染(IAI,17例)及尿路感染(UTI,1例)患者中分离出675株非重复AB,利用生物信息学方法鉴定其KL型别和耐药基因;采用琼脂或微量肉汤稀释法测定不同抗生素对675株AB的最低抑菌浓度;用简单随机抽样法从不同KL型别中各抽取10株菌进行全血存活实验;分析感染不同KL型别患者的住院时间和临床结局等差异。结果675例患者的年龄为(59±20)岁,男性460例;流行KL型别包括KL2(22.0%,149株)、KL3(17.5%,118株)、KL210(7.0%,47株)和KL160(7.0%,47株),其余为非流行KL型别(46.5%,314株)。4种流行KL型别对多数抗生素的耐药率均高于非流行KL型别(均P<0.05),KL2型别(92.6%,113株)对磺胺甲噁唑+甲氧苄啶的耐药率高于KL3型别(55.9%,66株)(P<0.05);KL2(87.2%,130株)和KL210型别(91.5%,43株)对米诺环素的耐药率高于KL3(67.8%,80株)和KL160型别(66.0%,31株)(均P<0.05)。KL2型别全血存活能力[(58.36±20.33)%]强于其他KL型别(均P<0.05)。KL2型别感染患者的病死率为30.9%(46例),高于感染KL3(11.9%,14例)及KL210型别(6.4%,3例)者(均P<0.05)。KL2型别感染患者的住院时间[M(Q1,Q3)]为46.00(26.50,74.00)d,长于感染KL3[30.00(15.25,40.75)d]、KL210[27.00(21.00,44.00)d]、KL160[27.00(20.00,34.00)d]以及非流行KL型别[25.00(12.00,40.00)d]者(均P<0.05)。结论AB不同KL型别在耐药表型及感染患者临床预后方面存在差异,其中KL2型别的耐药率较高,且感染患者的临床预后不佳。

关键词： 免疫球蛋白   肝衰竭   诊断价值  

摘要： 目的分析血清免疫球蛋白(Ig)检测在评估肝衰竭(LF)患者病情中的应用价值。方法选取2021年5月至2024年5月,由安阳市中医院和安阳市第五人民医院接诊的80例LF患者作为观察组,依据病程分为早期组(n=31,病程1~10天)、中期组(n=27,病程11~30天)和晚期组(n=22,病程31~45天)。同时纳入60名同期健康体检者为对照组,对比观察组、对照组以及观察组不同病程患者IgA、IgG及IgM浓度差异。分析影响LF发生的影响因素以及血清IgA、IgG、IgM水平单独及联合检测对LF的预测价值。结果观察组IgA、IgM和IgG水平均高于对照组,差异有统计学意义(P<0.05)。随着病情的加重,观察组患者的IgA、IgG和IgM水平均呈升高趋势,其中晚期组IgA、IgG和IgM水平均高于早、中期组,中期组IgA、IgG和IgM水平均高于早期组,差异有统计学意义(P<0.05)。观察组治疗后血清IgA、IgG、IgM水平与治疗前比较明显降低,差异有统计学意义(P<0.05)。Logistic回归分析结果显示,血清IgA、IgG和IgM水平升高是LF发生的相关因素。血清IgA、IgG及IgM水平单独预测LF的AUC分别为0.708、0.749和0.762,联合诊断LF的AUC为0.834。结论血清Ig水平的变动与LF发生发展过程均具有关联性,检测该指标可为临床决策提供支持。

关键词： AA   arachidonic acid   ALT   alanine aminotransferase   AST   aspartate aminotransferase   APAP   N-acetyl-p-aminophenol or acetamonophen   AMPK   AMP-activated protein kinase   Arg-1   arginase-1   BMDMs   bone-marrow-derived macrophages   CPLA2α   cytosolic phospholipase A2   CD36   cluster of differentiation 36   CD68   cluster of differentiation 68   COX   cyclooxygenases   CYP2E1   cytochrome P450 2E1   DHA   docosahexaenoic acid   ECP   eosinophilic cationic protein   GSH   glutathione   H&E   hematoxylin and eosin   HNF1α   hepatocyte nuclear factor1α   HNF4α   hepatocyte nuclear factor4α   HO-1   heme oxygenase-1   IHC   immunohistochemistry   IL   interleukin   INOS   inducible nitric oxide synthase   KC/CXCL1   keratinocyte chemoattractant/C-X-C motif chemokine receptor 1   LOX   lipoxygenases   LPS   lipopolysaccharides   Ly6C   lymphocyte antigen 6 complex locus C   Ly6G   lymphocyte antigen 6 family member G   KO   knockout   MASH   metabolic-associated steatohepatitis   MCP-1   monocyte chemoattractant protein-1   MCSF   macrophage colony-stimulating factor   MIP-1α   macrophage inflammatory protein-1α   MLKL   mixed lineage kinase domain-like protein   MPO   myeloperoxidase   Mφ   macrophages   NOX2   NADPH oxidase 2   NRF2   nuclear factor erythroid 2-related factor 2   PBMCs   peripheral blood mononuclear cells   PC   phosphatidylcholine   PE   phosphatidylethanolamine   PGE2   prostaglandin E2   PGD2   prostaglandin D2   15d-PGJ2   15-deoxy-∆-12,14-prostaglandin J2   PI   phosphatidylinositol   PLA2G6/iPLA2β   group VIA-calcium independent phospholipase A2   PLs   phospholipids   PS   phosphatidylserine   PT/CV   portal tract/central vein   QRT-PCR   quantitative real-time PCR   SM   sphingomyelin   UPLC-FLR   ultraperformance liquid chromatography-fluorescence   paracetamol toxicity   myeloid-PLA2G6   myelopoiesis   NADPH oxidase 2   cPLA2α   pro-resolving eicosanoids   tissue resolution  

摘要： Genetic PLA2G6 variants are associated with C-reactive protein in humans. Myeloid-specific PLA2G6-deficient (Pla2g6 M-/- ) mice show increased hepatic myeloperoxidase and recruitment of granulocytes in response to lipopolysaccharide (LPS). We hypothesized that Pla2g6 M-/- mice could be protected from acetaminophen (APAP) hepatotoxicity whereby neutrophils, eosinophils, and alternatively activated macrophages are reportedly protective. Herein, Pla2g6 M-/- mice treated with 300 mg/kg APAP for 24 h showed attenuated hepatic necrosis and plasma cytokines, and with elevated levels of Ly6C lo in peripheral blood mononuclear cells and plasma lipoxin A4. Remarkably, bone-marrow-derived macrophages (BMDMs) from untreated Pla2g6 M-/- mice exhibited elevated baseline expression of cPLA2α, NOX2, Rac1, Arg-1, phospho-MLKL, and iNOS protein, which was exacerbated by LPS in vitro . APAP administration preconditioned Pla2g6 M-/- BMDMs for further activation of enzymes involving in phagocytosis (Rac1 and phospho-MLKL) and eicosanoids (COX2 and A15LOXB). Pla2g6 M-/- BMDMs showed an increased release of pro-resolution lipid mediators lipoxin A4, PGE2, and 15d-PGJ2, which was further elevated by LPS in vitro or APAP in vivo . Phagocytic gene signatures (myeloperoxidase and NOX2) were also upregulated in livers of untreated and APAP-treated Pla2g6 M-/- mice. APAP protection in Pla2g6 M-/- mice was associated with increased proportion of neutrophils (Ly6G), eosinophils (eosinophilic cationic protein), and M2 macrophages (CD206) in/at the portal tract and central vein as determined by immunohistochemistry. Thus, myeloid-specific PLA2G6 deficiency preconditioned macrophages for eicosanoid and phagocytic pathways rendering protection against APAP hepatotoxicity. Our results may be applicable to patients with PLA2G6 mutations, and PLA2G6 inhibition specifically in myeloid cells may represent a new strategy to alleviate APAP poisoning.