Objective To investigate the value of cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) in diagnosis and prognosis in patients with sepsis.Methods Clinical data of patients admitted to intensive care unit (ICU) of the First Hospital of Hebei Medical University from December 2014 to December 2016 were retrospectively analyzed. According to the severity of sepsis, the patients were divided into three groups: sepsis patients, severe sepsis patients and septic shock patients, and 100 healthy persons were enrolled as control group. Levels of serum CRISPLD2, procalcitonin (PCT) and C-reactive protein (CRP), acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, and 28-day prognosis were recorded. Analysis of the correlation between CRISPLD2 and PCT, CRP, APACHEⅡscore, SOFA score was done. The receiver operating characteristic (ROC) curve was plotted for the CRISPLD2 value for the diagnosis and prognosis in patients with sepsis.Results A total of 115 patients with sepsis were enrolled in this study, including 52 sepsis, 48 severe sepsis, and 15 septic shock; 29 patients died after 28 days, 28-days mortality rate was 25.2%. There was no significant difference in CRISPLD2 between sepsis and healthy control group (mg/L: 204.1±74.5 vs. 211.3±12.0, P > 0.05); the level of CRISPLD2 in septic shock group was significantly lower than that in sepsis group and severe sepsis group (mg/L: 139.0±55.0 vs. 240.2±89.6, 233.0±8.9, bothP < 0.05). The level of PCT, CRP and APACHE Ⅱ score, SOFA score in sepsis patients were significantly higher than those in healthy control group, and increased with the severity of sepsis. There was no statistically significant difference in CRISPLD2 level between the dead and the survival of sepsis, and the levels of PCT and CRP in death group were significantly higher. The levels of CRISPLD2 were significantly negative correlated with the levels of PCT, CRP, APACHE Ⅱ score and SOFA score (r values were -0.089,-0.431, -0.115, -0.201, respectively, allP < 0.05). It was shown by ROC curve analysis that the area under ROC curve (AUC) and 95% confidence interval (95%CI) of CRISPLD2, PCT, CRP for diagnosis of sepsis were 0.907 (0.871-0.944), 0.922 (0.886-0.958), 0.916 (0.878-0.954) respectively, allP = 0.000; when the cut-off value of CRISPLD2 > 216.0 mg/L, the sensitivity was 96.7%, and the specificity was 92.6%, which power lied between PCT and CRP. The AUC of CRISPLD2 for prognosis was significantly lower than that of PCT [0.617 (0.507-0.727) vs. 0.786 (0.668-0.903),P <0.01]; when the cut-off value of CRISPLD2 was 103.5 mg/L, the sensitivity was 100%, and the specificity was 25.6%. Conclusion CRISPLD2 is a potential biomarker in sepsis, but cannot predict the prognosis of patients with sepsis.

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.

Objective To evaluate the accuracy of serum pro-adrenomedullin (pro-ADM) concentration in predicting sepsis at different degrees of severity.Methods A total of 145 patients of both sexes,aged 18-64 yr,who were admitted to intensive care unit (ICU) of the First Hospital of Hebei Medical University from March 2015 to April 2017,with length of ICU stay＞24 h,were enrolled.The patients were divided into 3 groups according to the Sequential Organ Failure Assessment (SOFA) score within 24 h after admission to ICU:2＜SOFA score ≤ 6 mild sepsis group (n =50),6＜SOFA score ≤ 12 moderate sepsis group (n =50) and SOFA score＞ 12 severe sepsis group (n =45).Peripheral venous blood samples were collected immediately after admission to hospital for determination of serum pro-ADM concentrations by enzyme-linked immunosorbent assay.The receiver operating characteristic (ROC) curve of pro-ADM in predicting sepsis at different degrees of severity was plotted,and the area under the curve and 95％ confidence interval,cut-off value,sensitivity and specificity were calculated.Results The serum pro-ADM concentrations were significantly increased with the severity of sepsis,and the length of ICU stay was prolonged with the severity of sepsis (P＜0.05).In mild sepsis group,the area under the ROC curve was 0.770,95％ confidence interval 0.591-0.949,sensitivity 0.725,specificity 0.700 and cut-off value 6.45 nmol/L.In moderate sepsis group,the area under the ROC curve was 0.776,95％ confidence interval 0.645-0.907,sensitivity 0.813,specificity 0.760,cut-off value 8.30 nmol/L.In severe sepsis group,the area under the ROC curve was 0.83,95％ confidence interval 0.715-0.963,sensitivity 0.73,specificity 0.800,cut-off value 5.70 nmol/L.Conclusion Serum pro-ADM concentration can be used as a reliable index in predicting sepsis at different degrees of severity.

Objective:To explore the value of plasma soluble leukocyte differentiation antigen 14 subtype(Presepsin) combined with neutrophil gelatinase associated lipocalin(NGAL) in the early diagnosis and prognosis of sepsis in children.Methods:A total of 94 children with sepsis admitted to our hospital from June 2017 to October 2020 were selected, 41 children with shock were classified as septic shock group, and 53 children without shock were classified as sepsis group.Another 41 healthy children in our hospital during the same period were selected as the control group.The plasma levels of Presepsin, NGAL, procalcitonin(PCT) and C-reactive protein(CRP)were detected in three groups.The pediatric critical illness score and sequential organ failure(SOFA)score of children with sepsis were recorded.According to the mortality of the children within 28 days of admission, they were divided into survival group( n=75)and death group( n=19). The plasma levels of Presepsin, NGAL, PCT and CRP, pediatric critical illness score and SOFA score were compared between the survival group and the death group.Pearson test and receiver operating characteristic curve were used to analyze the correlation between plasma Presepsin, NGAL and pediatric critical illness score, SOFA score, and the predictive value of early diagnosis and prognosis of sepsis in children. Results:The levels of plasma Presepsin, NGAL, PCT and CRP in sepsis group and septic shock group were higher than those in control group, and those in septic shock group were higher than those in sepsis group( P<0.05). The plasma levels of Presepsin, NGAL, PCT, CRP and SOFA scores in death group were higher than those in survival group, and the pediatric critical illness score in death group was lower than that in survival group( P<0.05). Plasma Presepsin and NGAL were negatively correlated with pediatric critical illness score( r=-0.676, P<0.001; r=-0.664, P<0.001), and positively correlated with SOFA score( r=0.781, P<0.001; r=0.749, P<0.001). When the plasma Presepsin level was 468.91 ng/L, the sensitivity of area under curve(AUC) for sepsis diagnosis was 85.6% and the specificity was 77.5%.When the plasma NGAL level was 38.94 ng/mL, the sensitivity of AUC for sepsis diagnosis was 82.4%, and the specificity was 65.8%.The AUC of plasma Presepsin combined with NGAL for early diagnosis of sepsis was 0.912(95% CI 0.865 to 0.959), which was higher than of plasma Presepsin of 0.857(95% CI 0.785 to 0.928) and the AUC of NGAL of 0.761(95% CI 0.680 to 0.841). When the plasma Presepsin level was 816.92 ng/L, the sensitivity for predicting the prognosis of sepsis was 73.2% and the specificity was 76.1%.When the plasma NGAL level was 51.27 ng/mL, the sensitivity for predicting the prognosis of sepsis was 67.4% and the specificity was 68.0%.The AUC of plasma Presepsin combined with NGAL to predict the prognosis of sepsis was 0.891(95% CI 0.816 to 0.966), which was higher than the AUC of plasma Presepsin of 0.795(95% CI 0.698 to 0.892) and NGAL of AUC 0.714(95% CI 0.577 to 0.851). Conclusion:Clinical detection of plasma Presepsin and NGAL levels is helpful to early diagnosis of sepsis and judge the severity of the disease in children, which has guiding significance in evaluating the prognosis, and is beneficial to improve the prognosis.