Sepsis is an infection-caused systemic inflammatory response syndrome, with relatively high morbidity and fatality rate. Early diagnosis and treatment are vital for prevention and treatment of sepsis. However, there are no simple clinical biomarkers that could rapidly and effectively detecting sepsis.

To assess the combined predictive value of toll-like receptor 4 (TLR4) in peripheral blood mononuclear cells and serum procalcitonin (PCT) for sepsis.

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.

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.

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.

脓毒症是由感染引起的全身炎症反应综合征，其发病率和致死率均较高，早期诊断和治疗是防治脓毒症的关键，但目前临床缺乏简便、快速、有效诊断脓毒症的检查指标。

探讨外周血单个核细胞Toll样受体4（TLR4）基因检测联合血清降钙素原（PCT）对脓毒症的诊断价值。

选取2020年10月至2021年11月武汉大学人民医院收治的110例脓毒症患者为脓毒症组，同期113例感染性疾病患者为非脓毒症组，95例体检健康者为对照组。将脓毒症患者依据休克情况分为非休克亚组和合并休克亚组。收集并分析三组实验室检查指标；分别测定三组外周血单个核细胞TLR4 mRNA和血清PCT水平；评估非脓毒症组和脓毒症组的快速序贯器官衰竭评分（qSOFA），分析两组间感染病原和感染部位的差异；采用受试者工作特征（ROC）曲线及ROC曲线下面积（AUC）分析外周血单个核细胞TLR4 mRNA、PCT单独与联合检测对脓毒症的诊断价值。

三组红细胞计数（RBC）、白细胞计数（WBC）、中性粒细胞计数（NEU）、血红蛋白（Hb）、血细胞比容（HCT）、血小板计数（PLT）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、直接胆红素（DBiL）比较，差异有统计学意义（P<0.05）。其中脓毒症组WBC、NEU、ALT、AST、DBiL较非脓毒症组、对照组均升高（P<0.05）；脓毒症组RBC、Hb、HCT、PLT较非脓毒症组、对照组均降低（P<0.05）。非脓毒症组和脓毒症组qSOFA比较，差异有统计学意义（Z=-3.128，P=0.002）。脓毒症组和非脓毒症组患者感染最多的病原微生物均为革兰阴性菌，感染最多的部位均为肺；两组感染病原、感染部位比较，差异均有统计学意义（P=0.033、0.003）。脓毒症组外周血单个核细胞TLR4 mRNA和PCT水平高于非脓毒症组和对照组（P<0.01）；非脓毒症组外周血单个核细胞TLR4 mRNA和PCT水平均高于对照组（P<0.01）。脓毒症组革兰阳性菌、革兰阴性菌、真菌和其他病原菌患者外周血单个核细胞TLR4 mRNA分别为0.154（0.302）、0.139（0.493）、0.119（0.206）和0.151（0.336），脓毒症组4种感染病原患者TLR4 mRNA比较，差异无统计学意义（H=0.378，P=0.945）。非休克亚组（35例）和合并休克亚组（75例）患者TLR4 mRNA水平分别为0.118（0.323）和0.210（0.330），两亚组TLR4 mRNA水平比较，差异有统计学意义（Z=1.473，P=0.026）。TLR4 mRNA单独诊断脓毒症的AUC为0.813时，对应的截断值为0.056，灵敏度为80.00%，特异度为68.97%，约登指数为0.489 7；血清PCT单独诊断脓毒症的AUC为0.818时，对应的截断值为0.070 μg/L，灵敏度为87.63%，特异度为75.94%，约登指数为0.635 6；联合检测诊断脓毒症的AUC为0.888时，灵敏度为68.04%，特异度为93.10%，约登指数为0.611 4。

脓毒症患者多项血常规和生化指标存在异常。外周血单个核细胞TLR4 mRNA、PCT可作为脓毒症的辅助诊断指标，两项指标联合检测可提高对脓毒症的诊断效能，具有较高的临床价值。