Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population

BACKGROUND: Triggering receptor expressed on myeloid cells-1(TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify infl ammation and serves as a critical mediator of infl ammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock.METHODS: We genotyped two TREM-1 single nucleotide polymorphisms(SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis.RESULTS: TREM-1 rs2234246 A allele in the promoter region was signifi cantly associated with the susceptibility of septic shock in recessive model(AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model(AG, OR=0.72, 95%CI 0.43–1.19, P=0.02; AA, OR=2.71, 95%CI 1.00–7.42; P=0.03). However, in three inherited models(dominant model, recessive model, and codominant model), none of the assayed loci was signif icantly associated with the prognosis of septic shock. The nonsurvivor group demonstrated higher plasma IL-6 levels(99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P<0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/m L, AG 85.4±43 pg/m L, and GG 65.3±30.7 pg/m L(P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were signifi cantly higher than those in patients with GG genotypes(P<0.01).CONCLUSION: TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.

Relationship between expression of triggering receptor-1 on myeloid cells in intestinal tissue and intestinal barrier dysfunction in severe acute pancreatitis

BACKGROUND：Triggering receptor expressed on myeloid cells-1 （TREM-1） in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane- bound TREM-1 protein is increased in the pancreas, liver and kidneys of patients with severe acute pancreatitis （SAP）, suggesting that TREM-1 may act as an important mediator of inflammation and subsequent extra-pancreatic organ injury. This study aimed to investigate the relationship between the expression of TREM-1 in intestinal tissue and intestinal barrier dysfunction in SAP. METHODS： Sixty-four male Wistar rats were randomly divided into a sham operation group （SO group, n=32） and a SAP group （n=32）. A SAP model was established by retrograde injection of 5% sodium deoxycholate into the bile-pancreatic duct. Specimens were taken from blood and intestinal tissue 2, 6, 12, and 48 hours after operation respectively. The levels of D-lactate, diamine oxidase （DAO） and endotoxin in serum were measured using an improved spectro-photometric method. The expression levels of TREM-1, interleukin-1β （IL-1β）, and tumor necrosis factor-α （TNF-α） mRNA in terminal ileum were detected by real-time reverse transcription-polymerase chain reaction （RT-PCR）. Specimens of the distal ileum were taken to determine pathological changes by a validated histology score. The serum levels of D-lactate, DAO and endotoxin were significantly increased in each subgroup of SAP compared with the SO group （P〈0.01, P〈0.05）. The expression levels of TREM-1, IL-1β and TNF-a mRNA in the terminal ileum in each subgroup of SAP were significantly higher than those in the SO group （P〈0.01, P〈0.05）. The expression level of TREM-lmRNA was positively correlated with IL-1βand TNF-α mRNA （r=0.956, P=0.044; r=0.986, P=0.015）, but the correlation was not found between IL-1β mRNA and TNF-a mRNA （P=0.133）. Compared to the SO group, the pathological changes were aggravated significantly in the SAP group. CONCLUSIONS： The expression level of TREM-1 in intestinal tissue of rats with SAP was elevated, leading to the release of inflammatory mediators and intestinal mucosal injury. This finding indicates that TREM-I might play an important role in the development of intestinal barrier dysfunction in rats with SAP.

Expression of triggering receptor-1 in myeloid cells of mice with acute lung injury

BACKGROUND： Myeloid cell （TREM-1） is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury （ALl） by intraperitoneal injection of lipopolysaccharide （LPS） was established to observe the expression pattern of TREM-1 in lung tissue and the role of TREM-1 in pulmonary inflammatory response to ALl.METHODS： Thirty BALB/C mice were randomly divided into a normal control group （n=6） and an ALl group （n=24）. The model of ALl was made by intraperitonal injection of LPS in dose of 10 mg/ kg. Specimens from peripheral blood and lung tissue were collected 6, 12, 24 and 48 hours after LPS injection. RT-PCR was used to detect TREM-1 mRNA, and ELISA was employed for detection of TREM-1 protein and TNF-a protein, and HE staining was performed for the pathological Smith lung scoring under a light microscope.RESULTS： The expressions of TREM-1 mRNAin lung tissue and blood of the ALl group 6, 12, 24, and 48 hours after injection of LPS were higher than those in the control group. The levels of TREM- 1 protein and the levels of TNF-a protein in lung tissue of the ALl group 6, 12, 24, and 48 hours after LPS injection were higher than those of the control group; the level of TREM-1 protein peaked 12 hours after LPS injection, but it was not significantly correlated with the expression of TREM-1 mRNA （P=0.14）; the TNF-a concentration was positively correlated with TREM-1 levels in lung tissue and with Smith pathological score （r=0.795, P=0.001 ：r=0.499, P=0.034）, but not with the expression of TREM-1 mRNA （P=0.176）.CONCLUSION： The expression of TREM-1 mRNA in lung tissue of mice with ALl is elevated, and the expression of TREM-1 mRNA is related to the level of TNF-a and the severity of inflammatory response to ALl. The expressions of the TREM-1 gene are not consistent with the levels of TREM-1 protein, suggesting a new functional protein involved in immune regulation.

Transcriptome sequencing and experiments reveal the effect of formyl peptide receptor 2 on liver homeostasis

BACKGROUND Formyl peptide receptor 2(Fpr2)is an important receptor in host resistance to bacterial infections.In previous studies,we found that the liver of Fpr2-/-mice is the most severely damaged target organ in bloodstream infections,although the reason for this is unclear.AIM To investigate the role of Fpr2 in liver homeostasis and host resistance to bacterial infections.METHODS Transcriptome sequencing was performed on the livers of Fpr2-/-and wild-type(WT)mice.Differentially expressed genes(DEGs)were identified in the Fpr2-/-and WT mice,and the biological functions of DEGs were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Quantitative real time-polymerase chain reaction(qRT-PCR)and western blot(WB)analyses were used to further validate the expression levels of differential genes.Cell counting kit-8 assay was employed to investigate cell survival.The cell cycle detection kit was used to measure the distribution of cell cycles.The Luminex assay was used to analyze cytokine levels in the liver.The serum biochemical indices and the number of neutrophils in the liver were measured,and hepatic histopathological analysis was performed.RESULTS Compared with the WT group,445 DEGs,including 325 upregulated genes and 120 downregulated genes,were identified in the liver of Fpr2-/-mice.The enrichment analysis using GO and KEGG showed that these DEGs were mainly related to cell cycle.The qRT-PCR analysis confirmed that several key genes(CycA,CycB1,Cdc20,Cdc25c,and Cdk1)involved in the cell cycle had significant changes.The WB analysis confirmed a decrease in the expression of CDK1 protein.WRW4(an antagonist of Fpr2)could inhibit the proliferation of HepG2 cells in a concentration dependent manner,with an increase in the number of cells in the G0/G1 phase,and a decrease in the number of cells in the S phase.Serum alanine aminotransferase levels increased in Fpr2-/-mice.The Luminex assay measurements showed that interleukin(IL)-10 and chemokine(C-X-C motif)ligand(CXCL)-1 levels were significantly reduced in the liver of Fpr2-/-mice.There was no difference in the number of neutrophils,serum C-reactive protein levels,and liver pathology between WT and Fpr2-/-mice.CONCLUSION Fpr2 participates in the regulation of cell cycle and cell proliferation,and affects the expression of IL-10 and CXCL-1,thus playing an important protective role in maintaining liver homeostasis.

AduoLa Fuzhenglin Down-regulates Microwave-induced Expression of β_1-adrenergic Receptor and Muscarinic Type 2 Acetylcholine Receptor in Myocardial Cells of Rats

This paper is aimed to study the effect of ADL on expression of ~z-AR and Mz-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect the expression of ~I-AR and Mz-AchR in myocardial cells at 7 and 14 d after microwave exposure. The results show that the expression level was higher in microwave exposure group and 0.75 g/（kg.d） ADL group than in sham operation group and significantly lower in 1.5 and 3.0 g/（kg.d） ADL groups than in microwave group. So we have a conclusion that the expression of I^z-AR and Mz-AchR is down-regulated in myocardial cells of rats exposed to microwave radiation. ADL can protect rats against microwave-induced heart tissue injury.

Blockade of cholecystokinin-2 receptor and cyclooxygenase-2 synergistically induces cell apoptosis, and inhibits the proliferation of human gastric cancer cells in vitro

Gastrin and cyclooxygenase-2(COX-2) playimportant roles in the carcinogenesis and progression ofgastric cancer.However,it remains unknown whether the combination of cholecystokinin-2(CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer.Here,we demonstrated that the combination of AG-041R(a CCK-2 receptor antagonist) plus NS-398(a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition,apoptosis induction,down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells.These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.(C)2008 Elsevier Ireland Ltd.All rights reserved.

Cyclosporin A impairs dendritic cell migration by regulating chemokine receptor expression and inhibiting cyclooxygenase-2 expression

Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair cytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow-derived DCs toward macrophage inflammatory protein-3beta (MIP-3beta) and induces them to retain responsiveness to MIP-1alpha after lipopolysaccharide (LPS)-stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs chemokine receptor and cyclooxygenase-2 (COX-2) expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 (PGE2) reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of chemokine receptor and cyclooxygenase-2 (COX-2) expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of chemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.

The triggering receptor expressed on myeloid cells 2-apolipoprotein E signaling pathway in diseases

Triggering receptor expressed on myeloid cells 2(TREM2)is a membrane receptor on myeloid cells and plays an important role in the body’s immune defense.Recently,TREM2 has received extensive attention from researchers,and its activity has been found in Alzheimer’s disease,neuroinflammation,and traumatic brain injury.The appearance of TREM2 is usually accompanied by changes in apolipoprotein E(ApoE),and there has been a lot of research into their structure,as well as the interaction mode and signal pathways involved in them.As two molecules with broad and important roles in the human body,understanding their correlation may provide therapeutic targets for certain diseases.In this article,we reviewed several diseases in which TREM2 and ApoE are synergistically involved in the development.We further discussed the positive or negative effects of the TREM2-ApoE pathway on nervous system immunity and inflammation.

血清可溶性髓系细胞触发性受体1、白细胞介素-21、25羟基维生素D在炎症性肠病患儿中的表达及相关性

目的探讨血清可溶性髓系细胞触发性受体1(sTREM-1)、白细胞介素-21(IL-21)、25羟基维生素D[25(OH)D]在炎症性肠病患儿中的表达及相关性。方法选取107例炎症性肠病患儿纳入观察组,另选取同期53例健康体检儿童纳入对照组,依照疾病活动性将观察组患儿分为活动期组54例和缓解期组53例,分别比较观察组与对照组、活动期组与缓解期组sTREM-1、IL-21、25(OH)D表达水平,采用Kendall's tau-b法分析sTREM-1、IL-21、25(OH)D与炎症性肠病活动性的相关性;采用受试者工作特征(ROC)曲线分析sTREM-1、IL-21、25(OH)D诊断炎症性肠病和预测炎症性肠病活动期的曲线下面积(AUC)、敏感度、特异度。结果观察组血清sTREM-1、IL-21水平高于对照组,25(OH)D水平低于对照组,差异有统计学意义(P<0.05)。活动期组血清sTREM-1、IL-21水平高于缓解期组,25(OH)D水平低于缓解期组,差异有统计学意义(P<0.05)。Kendall′s tau-b相关性分析显示,sTREM-1、IL-21与炎症性肠病活动性呈正相关(r=0.460、0.484,P<0.05),25(OH)D与炎症性肠病活动性呈负相关(r=-0.434,P<0.05)。ROC曲线显示,sTREM-1、IL-21、25(OH)D和三者联合诊断炎症性肠病的AUC分别为0.791、0.852、0.808和0.862,敏感度分别为74.80%、81.30%、75.50%和81.30%,特异度分别为75.50%、75.50%、81.30%和79.20%;sTREM-1、IL-21、25(OH)D和三者联合预测炎症性肠病活动期的AUC分别为0.821、0.840、0.799和0.840,敏感度分别为79.60%、75.90%、77.40%和87.00%,特异度分别为79.20%、75.50%、83.30%和79.20%。结论血清sTREM-1、IL-21、25(OH)D水平与儿童炎症性肠病的发生与发展密切关联,动态监测其水平有助于为临床诊断炎症性肠病和评估患儿病情进展提供重要参考依据。

髓系细胞触发受体2在高糖处理的小胶质细胞中的表达及作用

目的 探索高糖条件下小胶质细胞中髓系细胞触发受体2(triggering receptor expressed on myeloid cells 2, TREM2)的表达情况,以及TREM2在高糖条件下小胶质细胞增殖、迁移和吞噬中的作用。方法 小胶质细胞分为对照组、高糖处理组(67.5 mmol/L葡萄糖,24 h),检测小胶质细胞数量、Iba1和TREM2的表达水平;转染TREM2的siRNA,检测小胶质细胞增殖和迁移能力的变化;加入带有荧光标签的淀粉样蛋白β(Aβ),观察小胶质细胞对Aβ吞噬能力的影响。结果 与正常小胶质细胞相比,高糖处理后小胶质细胞的数量明显下降(P<0.001),而TREM2和Iba1表达显著升高(P<0.001)。高糖和TREM2均不影响小胶质细胞的增殖能力。与正常组相比,高糖处理后小胶质细胞迁移能力下降(P<0.05),而TREM2对高糖小胶质细胞的迁移能力无显著影响。与正常小胶质细胞相比,高糖处理组小胶质细胞对Aβ的吞噬能力显著下降(P<0.001),TREM2 siRNA敲减后高糖小胶质细胞对Aβ的吞噬能力进一步下降(P<0.001)。结论 高糖处理后小胶质细胞TREM2表达明显升高,其主要影响小胶质细胞对Aβ的吞噬能力。

髓系细胞触发受体2及其信号通路在恶性肿瘤中作用的研究进展

髓系细胞触发受体2(triggering receptors expressed on myeloid cells,TREM2)属于免疫球蛋白超家族成员,是一种跨膜受体,主要在髓系细胞和小胶质细胞中表达。TREM2与相应配体结合后,通过胞内接头蛋白DAP12/DAP10激活下游信号通路,起到重要的免疫信号传递作用。TREM2参与调节多种生物学过程,包括细胞吞噬、炎症反应和代谢过程等,在多种疾病的发生发展中发挥重要作用。近年研究表明,TREM2在恶性肿瘤的发生和发展过程中扮演重要角色。除了调控肿瘤细胞自身的生物学行为外,TREM2还能够调节肿瘤微环境内免疫细胞的活性和功能,参与抑制性免疫微环境的形成。本文着重概述TREM2对不同类型恶性肿瘤的调控作用,并对未来TREM2的靶向治疗相关研究进行展望,旨在为肿瘤防治领域的研究提供新的思路和观点。

糖尿病合并TREM2突变相关认知功能障碍的生物信息学分析

目的通过生物信息学分析探寻糖尿病(DM)合并髓系细胞触发受体-2(TREM2)突变相关认知功能障碍的核心基因及可能的治疗靶点。方法利用微阵列数据分析,分别得到糖尿病合并TREM2突变相关认知功能障碍2个疾病的差异基因并交集得到共同的差异基因。对其进行GO分析、KEGG和Reactome通路分析,利用在线数据库构建蛋白质-蛋白质相互作用网络(PPI);最后利用水迷宫检测糖尿病和TREM2对小鼠空间学习记忆能力的影响;利用蛋白质免疫印迹检测SNAP25表达的变化。结果在这2个数据集中,有19个基因变化相同,这些基因主要在与神经元和代谢相关的生物过程和通路富集。根据PPI分析结果,确定DNER、GFAP、GRM5、SNAP25为核心基因。Trem2敲除加重糖尿病模型小鼠空间学习记忆障碍,糖尿病小鼠海马SNAP25表达明显增加,Trem2敲除后SNAP25表达显著降低。结论本研究发现19个糖尿病合并认知功能障碍中TREM2相关基因,得到4个核心基因。这些结果为治疗糖尿病合并认知功能障碍患者提供新的实验依据。

超声心动图联合sST2、sTREM-1在急性ST段抬高型心肌梗死诊断中的临床价值

目的研究超声心动图指标联合血清可溶性致癌抑制因子2(sST2)、可溶性髓样细胞触发受体-1(sTREM-1)在急性ST段抬高型心肌梗死(STEMI)诊断中的临床价值。方法选取2021年9月至2022年9月在河北省沧州中西医结合医院治疗的90例急性STEMI患者作为STEMI组,选取同期冠状动脉造影检查结果为阴性的90例胸痛患者为对照组,比较两组超声心动图指标左室射血分数(LVEF)、左室舒张末期内径(LVEDD)和血清sST2、sTREM-1水平;采用Pearson相关分析急性STEMI患者LVEF、LVEDD与血清sST2、sTREM-1水平的相关性。采用受试者工作特征(ROC)曲线分析血清sST2、sTREM-1、LVEF、LVEDD诊断急性STEMI的价值。采用多因素Logistic回归分析急性STEMI发生的影响因素。结果STEMI组LVEF低于对照组,LVEDD高于对照组,差异均有统计学意义(P<0.05)。STEMI组CK-MB、cTnI水平及心率、心绞痛史比例高于对照组,差异均有统计学意义(P<0.05)。Pearson相关分析结果显示,急性STEMI患者LVEF与血清sST2、sTREM-1水平均呈负相关(r=-0.454、-0.463,P<0.05),LVEDD与血清sST2、sTREM-1水平均呈正相关(r=0.493、0.515,P<0.05)。LVEF、LVEDD及血清sST2、sTREM-1联合诊断急性STEMI的曲线下面积(AUC)为0.930,明显大于各项指标单独检测的AUC(Z=4.780、5.611、3.591、3.087,P<0.05)。多因素Logistic回归分析结果显示,sST2≥24.91 ng/mL、sTREM-1≥36.65 pg/mL是急性STEMI发生的危险因素(P<0.05)。结论血清sST2、sTREM-1联合超声心动图对急性STEMI患者的诊断效能较好。

TREM2缺失加重小鼠肺缺血再灌注损伤的机制研究

目的:探讨2型髓系细胞触发受体(TREM2)对肺缺血再灌注损伤(LIRI)的影响及其可能的调控机制。方法:将C57BL/6J雄性小鼠(WT)及TREM2敲除鼠(TREM2 KO)各12只,随机分成WT小鼠假手术组(WT组)、TREM2 KO小鼠假手术组(TREM2 KO组)、WT小鼠LIRI组(WT+LIRI组)、TREM2 KO小鼠LIRI组(TREM2 KO+LIRI组),每组6只。WT+LIRI组和TREM2 KO+LIRI组采用夹闭左肺肺门1 h,再灌注24 h的方法制备小鼠LIRI模型,WT组和TREM2 KO组仅开胸不夹闭肺门;通过蛋白免疫印迹(western blotting)、免疫荧光、实时荧光定量PCR(RT-qPCR)、苏木精—伊红(HE)染色、测定肺湿干质量比值(W/D)实验,评价敲除TREM2对小鼠肺缺血再灌注后组织损伤、炎症反应以及肺内巨噬细胞焦亡情况的影响。结果:TREM2敲除明显加重了LIRI后肺组织形态学改变,增加肺损伤评分(P<0.05),升高肺组织湿干质量比值(P<0.05),促进肺组织炎症因子白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)表达(P<0.05),增加LIRI后肺组织巨噬细胞焦亡标志物天冬氨酸特异性半胱氨酸蛋白酶-1(caspase-1)和成孔蛋白Gasdermin-D(GSDMD)表达(P<0.05)。结论:TREM2敲除加重LIRI,其机制可能与TREM2缺失引发caspase-1介导的肺内巨噬细胞焦亡有关。

基于TREM2介导的炎症信号通路观察电针缓解2型糖尿病干眼大鼠眼表感觉异常的作用机制

目的 揭示电针调控2型糖尿病干眼大鼠三叉神经节(TG)和三叉神经脊核尾状核(SpⅤc)中髓系细胞触发受体2(TREM2)介导的神经炎症信号通路缓解眼表感觉异常的潜在机制。方法 健康雄性SD大鼠高糖高脂饮食4周后,腹腔注射10 g·L^(-1)链脲佐菌素诱导建立2型糖尿病干眼大鼠模型。实验第12周造模成功的大鼠随机分为模型组、电针组、假针组、氟米龙组,并选择普通饲料喂养的健康雄性SD大鼠设为空白组,各组干预2周。造模前、造模后及干预后各组大鼠均行角膜荧光素钠染色(FL)、酚红棉线试验(PRT)、泪膜破裂时间(BUT)和角膜机械知觉(CTT)检查,观察各组大鼠TG和SpⅤc组织形态变化及TREM2阳性表达部位,检测在各组大鼠TG和SpⅤc中TREM2、白细胞介素-18(IL-18)和白细胞介素-1β(IL-1β)的mRNA表达。结果 造模后,与空白组比较,其余各组大鼠FL评分显著升高,PRT、BUT、CTT显著降低,差异均有统计学意义(均为P<0.01)。干预后,与模型组比较,电针组、氟米龙组大鼠FL评分显著降低,PRT、BUT、CTT显著升高,差异均有统计学意义(均为P<0.01),假针组以上指标差异均无统计学意义(均为P>0.05)。与电针组比较,氟米龙组、假针组大鼠PRT、CTT显著降低,假针组大鼠FL评分显著升高、BUT显著降低,差异均有统计学意义(均为P<0.01),氟米龙组大鼠FL评分、BUT差异无统计学意义(均为P>0.05)。与假针组比较,氟米龙组大鼠FL评分降低,PRT、BUT、CTT升高,差异均有统计学意义(P<0.05)。免疫荧光双标染色结果显示,TREM2在模型组大鼠TG和SpⅤc中激活的小胶质细胞上阳性表达。TG和SpⅤc的RT-PCR检测结果显示,与空白组比较,模型组、电针组、氟米龙组、假针组TG和SpⅤc中TREM2 mRNA表达降低,模型组TG和SpⅤc及假针组TG中IL-18和IL-1β mRNA,以及假针组SpⅤc中IL-18 mRNA表达增加,差异均有统计学意义(均为P<0.05)。与模型组比较,电针组、氟米龙组TG和SpⅤc中TREM2 mRNA表达增加,IL-18和IL-1β mRNA表达降低,差异均有统计学意义(均为P<0.05)。与电针组比较,假针组TG和SpⅤc中TREM2 mRNA表达降低,IL-18和IL-1β mRNA表达增加,差异均有统计学意义(均为P<0.05),氟米龙组TG和SpⅤc中TREM2、IL-18及IL-1β mRNA表达差异均无统计学意义(均为P>0.05)。与假针组比较,氟米龙组TG、SpⅤc中TREM2 mRNA表达增加,SpⅤc中IL-18 mRNA表达降低,差异均有统计学意义(均为P<0.05),氟米龙组TG、SpⅤc中IL-1β mRNA及TG中IL-18 mRNA表达差异均无统计学意义(均为P>0.05)。结论 电针通过调控TG和SpⅤc中TREM2介导的炎症信号通路,可有效缓解2型糖尿病干眼大鼠眼表感觉异常。

阿米卡星联合哌拉西林钠/他唑巴坦钠治疗重症肺炎的疗效及对血清HMGB1、sTREM-1、miR-233的影响

目的研究阿米卡星联合治疗哌拉西林钠/他唑巴坦钠治疗重症肺炎的疗效及对血清高迁移率族蛋白B1(HMGB1)、可溶性髓系细胞触发受体-1(sTREM-1)、微RNA(miR)-233的影响。方法前瞻性选择2018年1月至2022年12月黄石市中心医院收治的重症肺炎患者100例,依据随机数字表法分为阿米卡星组与对照组,各50例。两组均行祛痰、补液、扩张支气管及营养支持等常规治疗。在常规治疗基础上,对照组行哌拉西林钠/他唑巴坦钠治疗,阿米卡星组在对照组基础上行阿米卡星治疗。治疗14 d后,观察两组临床疗效、临床症状指标(发热时间、痰液颜色改变时间、肺部炎症吸收时间、机械通气时间及细菌清除率),观察两组治疗前及治疗14 d后血清指标[HMGB1、sTREM-1、miR-233水平、血清肿瘤坏死因子-ɑ(TNF-ɑ)、白细胞介素(IL)-6、L-10]、肺功能指标[用力肺活量(FVC)、第1秒用力呼气容积(FEV1)、功能残气量(FRC)、深吸气量(IC)]和不良反应情况。结果治疗14 d后,阿米卡星组总有效率为94.00%,高于对照组(76.00%),差异有统计学意义(P<0.05)。治疗14 d后,阿米卡星组发热时间、痰液颜色改变时间、肺部炎症吸收时间、机械通气时间为(3.26±0.35)、(4.19±0.44)、(8.24±0.85)、(8.64±0.89)d,均短于对照组[(6.31±0.66)、(7.08±0.73)、(9.31±0.95)、(10.78±1.30)d],细菌清除率为(92.75±9.54)%,高于对照组[(76.29±7.93)%],差异均有统计学意义(P<0.05)。治疗14 d后,阿米卡星组血清HMGB1、sTREM-1、miR-233水平为(112.08±13.96)μg/L、(42.84±4.50)ng/L、1.19±0.13,均低于对照组[(140.17±17.64)μg/L、(51.07±6.38)ng/L、(1.51±0.17)],差异均有统计学意义(P<0.05)。治疗14 d后,阿米卡星组的血清TNF-ɑ、IL-6水平为(1.01±0.12)ng/mL、(22.65±2.49)pg/mL,均低于对照组[(1.32±0.16)ng/mL、(26.83±2.94)pg/mL],阿米卡星组的IL-10水平为(15.98±1.82)pg/mL,均高于对照组[(12.74±1.53)pg/mL],差异均有统计学意义(P<0.05)。治疗14 d后,阿米卡星组FVC、FEV1、IC为(3.22±0.35)、(2.14±0.23)、(2.56±0.28)L,均大于对照组[(2.94±0.32)、(1.93±0.21)、(2.27±0.25)L],FRC为(2.02±0.22)L,小于对照组[(2.35±0.26)L],差异均有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(16.00%vs.8.00%)(P>0.05)。结论阿米卡星联合治疗哌拉西林钠/他唑巴坦钠治疗重症肺炎可有效清除致病菌,抑制炎症反应,缩短临床恢复时间,改善肺功能,降低血清HMGB1、sTREM-1、miR-233水平,疗效显著,安全性好。

Measuring Ca^(2+) influxes of TRPC1-dependent Ca^(2+) channels in HL-7702 cells with Non-invasive Micro-test Technique

AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a normal human liver cell line.METHODS： Net Ca^2＋ fluxes were measured with NMT, a technology that can obtain dynamic information of specific/selective ionic/molecular activities on material surfaces, non-invasively. The expression levels of TRPCl were increased by liposomal transfection, whose effectiveness was evaluated by Western-blotting and single cell reverse transcription-polymerase chain reaction.RESULTS： Ca^2＋ influxes could be elicited by adding 1 mmol/L CaCl2 to the test solution of HL-7702 cells. They were enhanced by addition of 20 μmol/L noradrenalin and inhibited by 100 μmol/L LaCl3 （a non-selective Ca^2＋ channel blocker）; 5 μmol/L nifedipine did not induce any change. Overexpression of TRPCl caused increased Ca^2＋ influx. Five micromoles per liter nifedipine did not inhibit this elevation, whereas 100 μmol/L LaCI3 did.CONCLUSION： In HL-7702 cells, there is a type of TRPCl-dependent Ca^2＋ channel, which could be detected v/a NMT and inhibited by La^3＋.

镍纹蛋白样蛋白、可溶性髓样细胞触发受体-1水平与2型糖尿病患者颈动脉粥样硬化程度的相关性

目的 探究镍纹蛋白样蛋白(METRNL)、可溶性髓样细胞触发性受体1(sTREM-1)水平与2型糖尿病(T2DM)患者颈动脉粥样硬化(CAS)严重程度的关系。方法 选取2021年12月—2023年12月承德市中心医院T2DM患者235例,根据是否伴有CAS分为CAS组(126例)和对照组(109例)。将CAS组根据CAS的严重程度细分为3个亚组[内膜中层厚度(IMT)增厚组(26例)、斑块形成组(41例)、颈动脉狭窄组(59例)]。收集所有患者临床资料和实验室指标检测结果,同时检测血清METRNL、sTREM-1水平。采用Spearman相关分析评估血清METRNL、sTREM-1与CAS严重程度的相关性。采用多因素Logistic回归分析评估CAS严重程度的影响因素。结果 与对照组比较,CAS组血清METRNL水平显著降低(P<0.05),血清sTREM-1水平显著升高(P<0.05)。IMT增厚组、斑块形成组、颈动脉狭窄组血清METRNL水平依次降低(P<0.001),sTREM-1水平依次升高(P<0.001)。METRNL与CAS严重程度呈负相关性(rs=-0.422,P<0.05),sTREM-1与CAS严重程度呈正相关(rs=0.535,P<0.05)。高血压史、sTREM-1、糖化血红蛋白(Hb A1c)、低密度脂蛋白胆固醇(LDL-C)是CAS严重程度(颈动脉狭窄)的危险因素[比值比(OR)值分别为3.354、2.165、1.642、1.943,95%可信区间(CI)分别为1.580~7.119、1.296~3.618、1.238~2.177、1.188~3.178,P<0.05],METRNL是保护因素(OR=0.768,95%CI为0.640~0.922,P<0.05)。结论 T2DM伴CAS患者血清METRNL水平降低,sTREM-1水平升高,与CAS严重程度密切相关。

纤维支气管镜肺泡灌洗液中sTREM-1、IL-32及PCT水平对呼吸机相关性肺炎病情及预后判断的价值

目的:探讨纤支镜支气管肺泡灌洗液中可溶性髓系细胞触发受体-1(sTREM-1)、白细胞介素32(IL-32)及降钙素原(PCT)水平与呼吸机相关肺炎(VAP)患者病情及预后判断的价值。方法:选取确诊的53例VAP患者作为VAP组;另选取同期实施机械通气但是未发生VAP的56例患者作为对照组。记录两组患者肺泡灌洗液中sTREM-1、IL-32、PCT水平、CPIS评分、APACHEⅡ评分,并探究其与患者病情和预后的相关性。结果:VAP组患者肺泡灌洗液sTREM-1、IL-32、PCT水平及CPIS评分、APACHEⅡ评分均高于对照组(P<0.05);VAP组患者肺泡灌洗液的sTREM-1、IL-32、PCT水平与CPIS评分正相关(r=0.614、0.603、0.621,P<0.05);VAP组患者肺泡灌洗液的sTREM-1、IL-32、PCT水平与APACHEⅡ评分正相关(r=0.414、0.463、0.409,P<0.05);53例VAP患者,经过28 d治疗,死亡17例、存活36例,死亡的VAP患者肺泡灌洗液sTREM-1、IL-32、PCT水平及CPIS评分、APACHEⅡ评分均高于存活组(P<0.05);肺泡灌洗液sTREM-1、IL-32、PCT水平预测VAP患者不良预后结局的受试者工作曲线下面积(AUC)分别为0.900、0.862、0.917。结论:VAP患者肺泡灌洗液中sTREM-1、IL-32、PCT水平升高,并且与患者肺部感染程度、病情危重程度正相关,对于预测患者不良结局具有较高的价值。

慢性心力衰竭患者血清CA125 GDF15 sTREM-1水平及其与心功能的相关性分析

目的:探究血清糖类抗原125(CA125)、生长分化因子-15(GDF-15)、可溶性髓样细胞触发受体-1(sTREM-1)在慢性心力衰竭患者中的表达及其与心功能的相关性分析。方法:选取2022年6月至2023年6月本院收治的CHF患者96例临床资料开展回顾性分析,其中轻中度心力衰竭组46例(NYHA分级为Ⅰ~Ⅲ级)、重度心力衰竭组50例(NYHA分级为Ⅳ级),另按2∶1比例选取同期本院检查健康体检者48名为健康对照组。比较各组血清CA125、GDF15、sTREM-1水平与心功能指标的差异,并分析血清CA125、GDF15、sTREM-1水平与心功能指标的相关性。并通过ROC曲线分析血清CA125、GDF15、sTREM-1水平诊断慢性心力衰竭的效能。结果:研究组CA125、GDF15、sTREM-1水平均高于对照组(P<0.05)。研究组FS、EF均低于对照组,LAD、LVEDD均高于对照组(P<0.05)。Person相关性分析显示,CA125、GDF15、sTREM-1均与FS、EF呈负相关(r=-0.605/-0.617、-0.516/-0.512、-0.572/-0.613,P<0.05),均与LAD、LVEDD呈正相关(r=0.827/0.818、0.819/0.834、0.846/0.878,P<0.05)。重度心力衰竭组CA125、GDF15、sTREM-1水平均高于轻中度心力衰竭组(P<0.05)。二元Logistic回归分析显示,血清CA125、GDF15、sTREM-1为重度心力衰竭的危险因素(P<0.05)。采用ROC分析血清CA125、GDF15、sTREM-1评估慢性心力衰竭严重程度的AUC、敏感度、特异度,分别为0.761、0.695、0.822,以预测评分绘制ROC曲线评估慢性心力衰竭严重程度的AUC为0.848,敏感度为84.0%、特异性为82.6%。结论:血清CA125、GDF15、sTREM-1在CHF患者中高表达,与心功能相关密切,可作为评估心力衰竭严重程度的有效指标,联合评估效果更好。