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           no simple clinical biomarkers that could rapidly and effectively detecting sepsis. Objective To assess the combined predictive
           value of toll-like receptor 4(TLR4) in peripheral blood mononuclear cells and serum procalcitonin(PCT) for sepsis. Methods
            One hundred and ten sepsis patients(sepsis group),113 patients with infection but without sepsis(non-sepsis group),
           and 95 healthy individuals(control group) were recruited from Renmin Hospital of Wuhan University from October 2020 to
           November 2021. Sepsis patients were divided into non-shock subgroup and shock subgroup according to the shock situation.
           Laboratory indicators,TLR4 in peripheral blood mononuclear cells and serum PCT of three groups were collected and analyzed.
           The quick Sepsis-related Organ Failure Assessment(qSOFA)score,infectious pathogens,and sites of infection of sepsis and
           non-sepsis groups were comparatively analyzed. The receiver operating characteristic curve(ROC)and area under the curve(AUC)
           were used to analyze the diagnostic value of TLR4 mRNA and PCT,alone and in combination,for sepsis. Results The levels of
           red blood cell (RBC) count,white blood cell(WBC) count,neutrophil count,hemoglobin(Hb),hematocrit (HCT),
           platelet count,alanine aminotransferase (ALT),aspartate aminotransferase(AST)and direct bilirubin(DBiL) differed
           significantly across the three groups(P<0.05). Sepsis group had significantly elevated levels of WBC count,neutrophil count,
           ALT,AST and DBiL,and significantly decreased levels of RBC count,Hb,HCT and platelet count compared with other two
           groups(P<0.05). Sepsis and non-sepsis groups had significant difference in qSOFA score(Z=-3.128,P=0.002). Gram-
           negative bacteria were the most prevalent pathogenic microorganism in both sepsis and non-sepsis groups,and lung was the most
           infected site. There were significant differences between the two groups in infected pathogenic microorganisms and infected sites
           (P=0.033,0.003). The levels of TLR4 mRNA in peripheral blood mononuclear cells and PCT showed a successive decrease in
           sepsis group,non-sepsis group and control group(P<0.01). The TLR4 mRNA levels in peripheral blood mononuclear cells of
           patients with sepsis induced by gram-positive bacteria,gram-negative bacteria,fungi and other pathogens in sepsis group were
           0.154(0.302),0.139(0.493),0.119(0.206)and 0.151(0.336),respectively,with no significant differences(H=0.378,
           P=0.945). The level of TLR4 mRNA differed significantly between shock subgroup(n=75)〔0.210 (0.330)〕 and non-
           subgroup hose without(n=35)〔0.118 (0.323)〕(Z=1.473,P=0.026). For the prediction of sepsis,the AUC of TLR4
           mRNA level was 0.813,with sensitivity of 80.00%,specificity of 68.97% and Youden index of 0.489 7,when the optimal cutoff
           value was defined as 0.056;the AUC of PCT was 0.818,with sensitivity of 87.63%,specificity of 75.94% and Youden index of
           0.635 6,when the optimal cutoff value was defined as 0.070 μg/L;the AUC of TLR4 mRNA combined with PCT was 0.888,
           with sensitivity of 68.04%,sensitivity of 93.10% and Youden index of 0.611 4. Conclusion Multiple routine blood indicators
           and biomarkers abnormalities were found in sepsis patients. TLR4 mRNA level was associated with the severity of sepsis. TLR4
           mRNA in peripheral blood mononuclear cells and serum PCT could be used as auxiliary predictors of sepsis,the combination of
           TLR4 mRNA and PCT could improve the predictive efficiency in sepsis,indicating a high clinical application value.
               【Key words】 Sepsis;Toll-Like receptor 4;Procalcitonin;Diagnosis;Noxae;Forecasting;Infections


               脓毒症是一种广义上由感染引起的全身炎症反应综                          特异度   [9-11] 。目前关于 TLR4 mRNA 联合血清 PCT 对
           合征,常伴发器官衰竭,是全世界危重症患者主要死                             脓毒症诊断价值的相关研究较少,本研究旨在探讨外周
           因之一   [1-2] 。脓毒症发病机制复杂,涉及炎性因子、                      血单个核细胞 TLR4 mRNA 联合血清 PCT 对脓毒症的诊
           氧化损伤、线粒体功能障碍、凋亡等其他因素                     [3] 。目     断价值,并分析 TLR4 mRNA 在不同脓毒症严重程度分
           前对于脓毒症的诊断有血培养、C 反应蛋白、降钙素                            级和感染不同病原时的水平变化,为临床诊断提供理论
           原(procalcitonin,PCT)等指标,但无法在单一指标                    依据,以达到对潜在脓毒症患者进行及早发现和干预的
           下及时准确诊断       [4] 。Toll 样受体(Toll-like receptors,    目的。
           TLRs)是一种免疫识别受体,是一种很有前途的新型生                          1 对象与方法
           物标志物    [5] 。脓毒症的常见感染菌是革兰阴性菌,其                      1.1 研究对象 选取 2020 年 10 月至 2021 年 11 月武
           细胞壁成分脂多糖(lipopolysaccharide,LPS)与 TLR4              汉大学人民医院收治的 110 例脓毒症患者为脓毒症组,
           结合,激发机体免疫炎性反应,导致多种促炎递质和细                            同期 113 例感染性疾病患者为非脓毒症组,95 例体检
           胞因子的分泌,如白介素(IL)-1β 和 IL-6,造成细                       健康者为对照组。纳入标准:(1)脓毒症组纳入符合
           胞因子风暴,导致机体损伤            [6] 。TLR4 mRNA 水平在脓         2016 年《第三版脓毒症与感染性休克定义国际共识》                    [1]
           毒症初期即上升,其水平被认为与炎症程度相关                     [7-8] 。   中脓毒症诊断标准的患者,即入院时临床诊断存在感
           PCT 是一种由 116 个氨基酸组成的多肽,是降钙素前体,                      染且序贯器官衰竭评分(SOFA)≥ 2 分或快速 SOFA
           可作为脓毒症级联反应的一部分,水平迅速升高,并在                            (qSOFA)≥ 2 分。(2)非脓毒症组选取入院主要诊
           脓毒症发病 12~48 h 后达到峰值,具有较高的灵敏度和                       断为感染性疾病的患者;(3)健康组选取同期健康体
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