The role of neutrophil CD 11b, soluble CD 14 subtype and mitochondrial coupling factor-6 in the risk stratification of disease outcome in neonatal sepsis and its clinical significance / 中国医师进修杂志

Objective:To investigate the role of neutrophil CD 11b (nCD 11b), soluble CD 14 subtype (sCD 14-St) and mitochondrial coupling factor-6 (CF-6) in the risk stratification of disease outcome in neonatal sepsis and its clinical significance. Methods:The clinical data of 121 septic neonates from July 2019 to March 2020 in Shanxi Children′s Hospital were retrospectively analyzed. According to the neonatal critical illness score (NCIS), the neonates were divided into non-critical group (NCIS>90 scores) with 35 cases, critical group (NCIS 70 to 90 scores) with 49 cases, very critical group (NCIS<70 scores) with 37 cases. There were 25 cases with poor prognosis (death), and 96 cases with good prognosis (survival). The C-reactive protein (CRP), procalcitonin (PCT), nCD 11b, sCD 14-St and CF-6 before treatment were detected. The correlation between nCD 11b, sCD 14-St, CF-6 and disease severity was analyzed by Spearman method; the value of nCD 11b, sCD 14-St and CF-6 in predicting poor disease outcome in sepsis neonates was analyzed by the receiver operating characteristic (ROC) curve. Results:The nCD 11b, sCD 14-St, CF-6, PCT and CRP in critical group and very critical group were significantly higher than those in non-critical group: (414.68 ± 93.29) and (532.74 ± 101.85) MFI vs. (325.45 ± 71.90) MFI, (892.40 ± 113.72) and (1 249.53 ± 95.41) ng/L vs. (784.66 ± 103.72) ng/L, (84.79 ± 28.35) and (121.66 ± 34.27) ng/L vs. (42.59 ± 13.51) ng/L, (19.24 ± 6.30) and (34.96 ± 11.95) μg/L vs. (8.89 ± 2.24) μg/L, (109.49 ± 36.77) and (247.13 ± 82.06) mg/L vs. (56.84 ± 17.25) mg/L; the indexes in very critical group were significantly higher than those in critical group, and there were statistical differences ( P<0.05). Spearman correlation analysis result showed that nCD 11b, sCD 14-St and CF-6 were positively correlated with disease severity in sepsis neonates ( r = 0.719, 0.813 and 0.823; P<0.01). The nCD 11b, sCD 14-St, CF-6, PCT and CRP in poor prognosis neonates were significantly higher than those in good prognosis neonates: (618.58 ± 146.92) MFI vs. (374.55 ± 120.03) MFI, (1 516.91 ± 194.38) ng/L vs. (828.13 ± 175.67) ng/L, (165.84 ± 25.63) ng/L vs. (62.51 ± 16.75) ng/L, (43.46 ± 10.14) μg/L vs. (20.19 ± 6.30) μg/L and (321.09 ± 94.56) mg/L vs. (88.24 ± 29.19) mg/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of nCD 11b, sCD 14-St and CF-6 for predicting poor disease outcome in sepsis neonates were 0.763, 0.796 and 0.838 (95% CI 0.678 to 0.836, 0.713 to 0.864 and 0.760 to 0.899), and the AUC of combination the 2 indexes was 0.921 (95% CI 0.858 to 0.962). Conclusions:The nCD 11b, sCD 14-St and CF-6 are associated with the disease severity and prognosis in sepsis neonates, and can be used as markers for risk stratification of disease outcome and assessment prognosis.

Progress of plasma soluble CD14 subtype in neonatal septicemia / 国际儿科学杂志

Neonatal sepsis is a common infectious disease in the neonatal period, and its morbidity and mortality are increasing year by year.Its etiology and pathogenesis have not been fully elucidated.In recent years, studies have confirmed that plasma soluble CD14 subtype(sCD14-ST)plays a certain role in the pathogenesis of neonatal sepsis, and has a certain value in its diagnosis and prevention.The study found that sCD14-ST could be used as an indicator for early auxiliary diagnosis of neonatal sepsis, and the expression of sCD14-ST was positively correlated with the degree of neonatal sepsis.Early detection of sCD14-ST can predict neonatal sepsis.This article reviews the research on sCD14-ST and its application in neonatal sepsis.

Caracterização funcional do gene codificador de proteína CD14 e do gene não codificador de proteína LINC01133 em linhagens celulares humanas de câncer de mama triplo negativo / Functional characterization of the CD14 protein-coding gene and the non-protein-coding LINC01133 gene in triple negative human breast cancer cell lines

Dentre os subtipos de câncer de mama, o triplo negativo (TNBC) é o que apresenta as maiores taxas de mortalidade, sendo, portanto, considerado um enorme desafio para a clínica. O uso de moléculas como marcadores tumorais vem auxiliando o clínico no diagnóstico, no prognóstico e, até mesmo, no tratamento do TNBC, sendo essenciais na redução de suas altas taxa de mortalidade. No entanto, um pequeno grupo de marcadores tumorais são validados na prática clínica, estimulando à busca por novos alvos, e sua caracterização funcional, como forma de se entender a Biologia desta doença. Assim, o objetivo deste trabalho é caracterizar funcionalmente o gene codificador de proteína CD14 e o gene não codificador de proteína LINC01133 em linhagens celulares humanas de TNBC, no intuito de descobrir o papel destas moléculas na progressão tumoral. Na primeira parte deste trabalho, analisou-se a expressão do CD14 frente à um painel de linhagens celulares que representam os diferentes subtipos dos tumores mamários. O CD14 exibiu elevados níveis de expressão nas linhagens nãotumorigênicas MCF10A e MCF12A e baixos níveis na linhagem triplo negativa Hs578T. A partir destes resultados, o CD14 foi superexpresso na linhagem Hs578T. Ensaios de caracterização funcional mostraram que a superexpressão do CD14 reduziu a capacidade migratória e invasiva das células, efeito que foi hipoteticamente relacionado ao aumento da expressão da E-caderina. No entanto, observou-se aumento no potencial tumorigênico, levando-nos a sugerir seu envolvimento num possível mecanismo utilizado pelas células para compensar a significativa redução do potencial migratório e invasivo. Os resultados obtidos indicam que o nível basal de expressão do CD14 observado na linhagem Hs578T é importante, podendo contribuir para a desenvolvimento primário do tumor, atuando como um oncogene. Na segunda parte deste trabalho, analisou-se a expressão de 10 RNAs longos não codificadores (lncRNAs), frente ao mesmo painel de linhagens descritoanteriormente. Dentre estes, o lncRNA LINC01133 exibiu baixos níveis de expressão nas linhagens não-tumorigênicas MCF10A e MCF12A e elevados níveis na linhagem triplo negativa Hs578T, sendo, então, escolhido como alvo de estudo. A partir destes resultados, decidimos superexpressar, de forma indutível, o LINC01133 na linhagem MCF10A e nocautear este gene, via sistema CRISPR/Cas9, na linhagem Hs578T. Ensaios de caracterização funcional mostraram que a superexpressão do LINC01133 na linhagem MCF10A reduziu a proliferação celular e inibiu o crescimento de colônias dependente de ancoragem, mas, em contrapartida, aumentou o crescimento de colônias independente de ancoragem e a capacidade migratória e invasiva destas células. No entanto, sugerimos que isto não seja suficiente para tornar estas células tumorigênicas e metastáticas. Por outro lado, o nocauteamento do LINC01133 na linhagem triplo negativa Hs578T aumentou de forma considerável todos os parâmetros de malignidade analisados. Baseado nos dados obtidos, sugerimos que o elevado nível de expressão do LINC01133 na linhagem Hs578T é importante na regulação negativa de processos relacionados com a progressão tumoral, atuando com um supressor tumoral. Os dados obtidos em nosso estudo contribuem para o enriquecimento de informações relacionadas à Biologia do TNBC, auxiliando, desta forma, no desenvolvimento de potenciais protocolos clínicos e terapêuticos utilizandos estes biomarcadores

Among the breast cancer subtypes, the triple negative (TNBC) displays the highest mortality rates, being, therefore, considered a major challenge for the clinic. The use of molecules as tumor markers has helped clinicians in the diagnosis, prognosis and even in treatment of TNBC, being essential in reducing its high mortality rate. However, a small group of tumor markers is validated in clinical practice, stimulating the search for new targets, and their functional characterization, as a way to understand the biology of this disease. Thus, the aim of this work is to functionally characterize the CD14 protein-coding gene and the non-protein-coding LINC01133 gene in human TNBC cell lines, in order to probe into the role of these molecules in tumor progression. In the first part of this work, the expression of CD14 was analyzed in a panel of cell lines that represent the different subtypes of breast tumors. High expression levels of CD14 were observed in the non-tumorigenic MCF10A and MCF12A lineages and low levels in the triple negative Hs578T lineage. Based on these results, CD14 was overexpressed in the Hs578T lineage. Functional characterization assays showed that CD14 overexpression reduced the migratory and invasive capacity of cells, an effect that was hypothetically related to increased E-cadherin expression. However, increased in the tumorigenic potential was observed, leading us to suggest its involvement in a possible mechanism used by cells to compensate for the significant reduction in the migratory and invasive potential. The results obtained indicate that CD14 expression basal level observed in the Hs578T lineage may be important to contribute to the primary development of tumor, thus acting as an oncogene. In the second part of this work, the expression of 10 long non-coding RNAs (lncRNAs) was analyzed against the same lineage panel described above. Among these, the LINC01133 lncRNA exhibited low expression levels in the non-tumorigenic MCF10A and MCF12A lineages and high levels in the triple negative Hs578T lineage, being, then, chosen as a target for this study. Based on these results, we decided toinducibly overexpress LINC01133 in the MCF10A lineage and knockout this gene, via the CRISPR/Cas9 system, in the Hs578T lineage. Functional characterization assays showed that overexpression of LINC01133 in the MCF10A lineage reduced cell proliferation and inhibited anchorage-dependent colony growth, but, on the other hand, increased anchorage-independent colony growth and the migratory and invasive capacity of these cells. However, we suggest that this is not sufficient to render these cells tumorigenic and metastatic. On the other hand, the knockout of LINC01133 in the triple negative Hs578T lineage considerably increased all the analyzed malignancy parameters. Based on the results obtained, we suggest that the high expression level of LINC01133 in the Hs578T lineage is important for down-regulation of processes related to tumor progression, acting as a tumor suppressor. The data obtained in our study contribute to the enrichment of information related to TNBC Biology, thus assisting in the development of potential clinical and therapeutic protocols using these biomarkers

Effects and significance of continuous hemoperfusion on patients with diquat poisoning / 中华危重病急救医学

Objective:To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance.Methods:A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO 2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. Results:Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO 2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (μg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (μmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO 2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ2 = 7.288, P = 0.007]. Conclusion:Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.

Effect of Shaoyaotang on Expressions of CD14, FADD and Caspase-8 in Colonic Tissues of Rats with Large Intestinal Damp-heat Syndrome of Ulcerative Colitis / 中国实验方剂学杂志

Objective:To observe the effect of Shaoyaotang on the contents of cell adhesion molecule-1 （ICAM-1） and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） in serum of large intestine damp-heat syndrome of ulcerative colitis （UC） in rats， and the gene and protein expressions of leukocyte differentiation antigen14 （CD14）， Fas-related death domain protein （FADD） and cysteinyl aspartate specific protease-8 （Caspase-8） in the focal colon tissue. Method:A total of 80 SPF Wistar rats were randomly divided into the blank group （<italic>n</italic>=10） and modeling group （<italic>n</italic>=70）. The large intestine damp-heat syndrome of UC rats was replicated by the combination of disease and syndrome， which was high-fat， high-sugar and spicy diets combined with 2， 4-dinitrobenzene sulfonic acid （DNBS） and ethanol. After successful modeling， the modeled groups were divided into model group， sulfasalazine （SASP）control group， and low， medium and high-dose Shaoyaotang groups by the method of random number table， with14 rats in each group. Low， medium and high doses of Sulfasalazine 0.2 g·kg^-1·d^-1 and Shaoyaotang （6， 12， 24 g·kg^-1·d^-1）were given by gavage. The blank group and the model group were given equal volume of normal saline for 21 days. The contents of serum ICAM-1 and TGF-<italic>β</italic>₁ were detected by enzyme-linked immunosorbent assay （ELISA）， the expressions of CD14， FADD and Caspase-8 mRNA in colon tissues were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the expressions of CD14， FADD and Caspase-8 protein in colon tissues were detected by Western blot. Result:Compared with the blank group， the serum ICAM-1 level in the model group were significantly increased， whereas the content of TGF-<italic>β</italic>₁ were significantly decreased （<italic>P</italic><0.05）. The relative expression levels of CD14， FADD， Caspase-8 mRNA and protein were significantly increased （<italic>P</italic><0.05）. Compared with the model group， the content of ICAM-1 in the serum of the rats in the medium， high-dose Shaoyaotang groups and the SASP group were significantly decreased， while the content of TGF-<italic>β</italic>₁ in the serum of the rats in the low， medium， high-dose Shaoyaotang groups and the SASP group were significantly increased （<italic>P</italic><0.05）. The expression levels of CD14， FADD， Caspase-8 mRNA and protein in each intervention group were significantly decreased （<italic>P</italic><0.05）， especially in the high-dose Shaoyaotang group and the SASP group. Conclusion:Shaoyaotang has a certain intervention effect on UC rats with large intestine damp-heat syndrome， and its mechanism may be related to the inhibition of CD14， FADD and Caspase-8 genes and proteins expression.

CD14 genotype and functional dichotomy of CD14+ and CD14- cells are associated with activated immune response and development of Chagas dilated cardiomyopathy

We aimed to investigate the association of CD14 -260C/T (rs2569190) polymorphism and Chagas cardiomyopathy and the functional characteristics of CD14+ and CD14- monocytes upon infection with Trypanosoma cruzi. We observed an association between the T- genotype (absence of allele -260T) related to low CD14 expression and the dilated cardiomyopathy type of Chagas disease. Furthermore, we observed that CD14- monocytes showed a more activated profile upon in vitro infection with T. cruzi than CD14+ monocytes. Our findings suggest that T- genotype is associated with susceptibility to develop Chagas dilated cardiomyopathy, likely linked to the T. cruzi-induced inflammatory profile of CD14- monocytes.

Onset of Coronary Heart Disease is Associated with HCMV Infection and Increased CD14 CD16 Monocytes in a Population of Weifang, China / 生物医学与环境科学（英文）

Objective@#To investigate the relationship between human cytomegalovirus (HCMV) infection and peripheral blood CD14 CD16 monocytes in the pathogenesis of coronary heart disease (CHD), and to elucidate the mechanism of pathogenesis in CHD by analyzing the correlation between infection, inflammation, and CHD, to provide a basis for the prevention, evaluation, and treatment of the disease.@*Methods@#In total, 192 patients with CHD were divided into three groups: latent CHD, angina pectoris, and myocardial infarction. HCMV-IgM and -IgG antibodies were assessed using ELISA; CD14 CD16 monocytes were counted using a five-type automated hematology analyzer; mononuclear cells were assessed using fluorescence-activated cell sorting; and an automatic biochemical analyzer was used to measure the levels of triglyceride, cholesterol, high- and low-density lipoprotein cholesterols, lipoprotein, hs-CRp and Hcy.@*Results@#The positive rates of HCMV-IgM and -IgG were significantly higher in the CHD groups than in the control group. HCMV infection affects lipid metabolism to promote immune and inflammatory responses.@*Conclusion@#HCMV infection has a specific correlation with the occurrence and development of CHD. The expression of CD14 CD16 mononuclear cells in the CHD group was increased accordingly and correlated with acute HCMV infection. Thus, HCMV antibody as well as peripheral blood CD14 CD16 mononuclear cells can be used to monitor the occurrence and development of CHD.

Clinical value of plasma presepsin level in early severity evaluation for acute pancreatitis patients / 中华胰腺病杂志

Objective@#To investigate the clinical value of plasma presepsin level in early severity evaluation for acute pancreatitis (AP) patients.@*Methods@#The clinical data of 67 patients with AP admitted in Second Affiliated Hospital of Wenzhou Medical University from December 2016 to January 2019 were prospectively selected. The patients were divided into mild AP group (MAP, n=36) and moderately severe and severe AP group (MSAP+ SAP, n=31) according to CTSI and with or without organ dysfunction and local or systemic complications on admission. Another 20 healthy normal subjects were selected as the control group. Plasma presepsin, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), serum amylase and calcium levels were measured within 2 hours, and the APACHEⅡ score was calculated within 24 hours of admission. Receiver operating characteristic curves(ROC) were plotted and the area under the curve (AUC) was calculated to assess the clinical value of presepsin, CRP, PCT, WBC, serum amylase and calcium for predicting the severity of AP patients, respectively.@*Results@#The plasma presepsin level in MAP, MSAP+ SAP and control group was (439.59±74.23)ng/L, (1097.82±93.15)ng/L and (97.31±21.57)ng/L, respectively. Plasma presepsin level in MAP and MSAP+ SAP patients with biliary pancreatitis were obviously higher than those patients with other etiological factors, and plasma presepsin level in MSAP+ SAP patients with hyperlipidemia-associated pancreatitis was significantly higher than those in the MAP group, and the difference was statistically significant (P<0.05). The AUC of plasma presepsin in the diagnosis of MSAP+ SAP was 0.873(95% CI 0.734-0.922), which was greater than the AUC values of CRP, PCT, WBC and serum calcium; the optimal cut-off value was 951.94 ng/L; the diagnostic sensitivity was 85.6%, which was superior to CRP, PCT, WBC and serum calcium; and the specificity was 76.2%, which was second to 78.9% of serum calcium.@*Conclusions@#Plasma presepsin level can be used as a sensitive indicator for early severity evaluation of AP patients, with a specificity only second to serum calcium.

T cell immunoglobulin and mucin domain-containing protein 3 inhibits interleukin-12 secretion by CD14+ monocytes from patients with psoriasis vulgaris / 中华皮肤科杂志

Objective@#To assess the role of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) in regulation of interleukin (IL) -12 secretion by CD14+ peripheral blood monocytes from patients with psoriasis vulgaris.@*Methods@#From November 2017 to March 2018, a total of 47 patients with psoriasis vulgaris (psoriasis group) and 19 healthy volunteers (control group) were enrolled from Shanxi Provincial People′s Hospital. Peripheral blood mononuclear cells (PBMC) were isolated, and stimulated with Toll-like receptor (TLR) ligands. TIM-3 expression and IL-12 secretion by CD14+ monocytes were measured by flow cytometry. After blockade of TIM-3 pathway by anti-TIM-3 neutralizing antibody, changes in the downstream signaling pathway molecules in and IL-12 secretion by CD14+ monocytes were investigated. Two independent samples t-test was used for comparison between two groups, and Pearson correlation test for correlation analysis.@*Results@#Under the unstimulated condition, the level of IL-12 secreted by CD14+ monocytes was very low, and the proportion of CD14+ TIM-3+ cells was significantly higher in the psoriasis group (12.20% ± 2.83%) than in the control group (9.91% ± 1.77%, t = 3.270, P = 0.001 7) . After the stimulation with TLR ligands, the proportion of CD14+ IL-12+ cells was significantly lower in the psoriasis group (13.49% ± 2.80%) than in the control group (28.97% ± 8.97%, t = 10.71, P < 0.000 1) , but the proportion of CD14+TIM-3+ cells was still higher in the psoriasis group (6.80% ± 1.11%) than in the control group (4.85% ± 1.37%, t = 6.064, P < 0.000 1) . The proportion of CD14+TIM-3+ cells was negatively correlated with that of CD14+ IL-12+ cells in both the control group and psoriasis group (r = -0.473, -0.371 respectively, both P < 0.05) . The TIM-3 pathway blockade could induce the decrease of suppressor of cytokine signaling 1 in CD14+ monocytes, increase the phosphorylation of signaling transducers and activators of transcription 1, and promote IL-12 secretion by CD14+ monocytes induced by keratinocytes isolated from psoriatic skin lesions.@*Conclusion@#TIM-3 plays a crucial role in the negative regulation of CD14+ monocyte-induced innate immune response in psoriasis.

Interaction of notch signaling pathway with toll-like receptor 4 on the function of CD14+ monocytes in chronic hepatitis C patients / 中华肝脏病杂志

Objective@#To observe the expressional changes in Notch signaling pathway and toll-like receptor 4 (TLR4) and their interactions on the functions of CD14+ monocytes in chronic hepatitis C patients.@*Methods@#A total of 24 treatment-naïve chronic hepatitis C cases and 10 healthy individuals, who visited Shaanxi Provincial People's Hospital from August to October 2017, were enrolled. Selected CD14+ monocytes were stimulated by the Notch signaling pathway inhibitor DAPT or transfected with TLR4 siRNA, and the levels of Notch1, Notch2, Hes1 and Hes5 mRNA were detected by real-time quantitative PCR. TLR4 protein levels and phosphorylation of NF-κB was detected by Western blot. ELISA was used to detect the level of cytokines secreted from CD14+ monocytes. A t-test or paired t-test was used for comparison between groups.@*Results@#The relative expression of Notch1 mRNA (3.97 ± 2.03 vs. 0.91 ± 0.76, P < 0.01) and downstream of Notch signaling pathway (5.96 ± 2.31 vs. 0.99 ± 0.45, P < 0.01), Hes1 mRNA and Hes5 mRNA (4.31 ± 1.05 vs. 0.84 ± 0.20, P < 0.01) in CD14+ monocytes of chronic hepatitis C patients was significantly higher than that of healthy individuals. The relative expression of TLR4 mRNA (5.14 ± 1.09 vs. 1.27 ± 0.39) and protein level in CD14+ monocytes of chronic hepatitis C patients were significantly higher than those of healthy individuals (P < 0.01). An inhibition of Notch signaling pathway with DAPT had reduced the relative expression level of TLR4 mRNA (2.58 ± 1.36 vs. 4.34 ± 1.88, P < 0.05), protein expression and phosphorylation of NF-B in CD14+ monocytes of chronic hepatitis C patients. Furthermore, the secretion level of MCP-1 [(94.32 ± 23.59) pg/ml vs. (64.07 ± 9.39) pg/ml, P < 0.01] and IL-8 [(12.54 ± 4.89) pg/ml vs. (7.92 ± 3.01) pg/ml, P < 0.05] was significantly reduced. TLR4 siRNA transfection reduced the expressions of Notch1 mRNA (2.09 ± 1.72 vs. 3.73 ± 1.75, P < 0.05), Hes1 (2.87 ± 0.84 vs. 5.54 ± 0.97, P < 0.01), and Hes5 (2.89 ± 0.93 vs. 4.51 ± 1.54, P < 0.01) in CD14+ monocytes of chronic hepatitis C patients.@*Conclusion@#Interaction of Notch signaling pathway with TLR4 can promote the function of CD14+ monocytes in chronic hepatitis C patients.

Diagnostic value and prognostic evaluation of presepsin for acute respiratory distress syndrome (ARDS) / 复旦学报（医学版）

Objective To assess the diagnostic and prognostic value of measuring presepsin in patients with acute respiratory distress syndrome (ARDS).Methods Plasma prsepsin was collected from 81 patients with ARDS,27 patients with cardiogenic pulmonary edema (CPE) and 20 healthy volunteers at enrollment.Levels of presepsin were measured using the PATHFAST(R) analysis system based on a chemiluminescent enzyme immunoassay (CLEIA).The differences of plasma prsepsin were compared between different groups.The 28-day mortality were followed in ARDS patients,and the characteristics of the surviors and non-surviors were compared.Results ARDS patients had significantly higher median levels of presepsin compared to CPE patients [926.89 (485.41-2 662.32)pg/mL vs.376.21 (247.16-568.52) pg/mL,P＜0.001] at enrollment.The difference between infected and non-infected ARDS patients did not showed statistical significance [(934.74 (456.44-3 322.51) pg/mL vs.798.12 (485.41-2 561.40) pg/mL,P--0.079).In ARDS patients,the presepsin levels of non-survivors was significantly higher than that of survivors [3 158.3 (963.91-4 489.33) pg/mL vs.729.09 (398.05-1 467.24) pg/mL,P＜0.001],and multivariate Logistic regression showed that presepsin (OR =1.51,P =0.027) was the independent predictor for 28-day mortality in ARDS patients with acute lung injury (ALI).Conclusions Presepsin was an effective indicator in diagnosing ARDS,and it also was a strong prognostic marker for short-term mortality in ARDS.

Macrophage IL-33 expression in macrophages of human chronic periapical periodontitis and apical cyst / 口腔疾病防治

Objective@#To observe the expression of interleukin-33 (IL-33) in macrophages of chronic periapical periodontitis and apical cyst tissue, and to provide a basis for the study of the pathogenesis of IL-33 in periapical diseases.@*Methods @#The apical tissues of 20 normal control group, 15 chronic periapical periodontitis group and 15 apical cyst group were collected for HE staining and optical microscopy respectively. CD14 was used as the marker of macrophages and double immunofluorescence staining was used to observe the changes of periapical tissues under fluorescence microscopy. The expression of IL-33 in CD14-positive macrophages was observed.@*Results@#The macrophage density (cell/mm 2) of IL-33 and CD14 positive expression in normal control group, chronic periapical periodontitis group and root cyst group were（23.81 ± 5.16,62.97 ± 8.54,119.83 ± 14.61) respectively, and there were significant differences among the three groups（F=87.17,P < 0.01）. The density of IL-33 and CD14 positive macrophages in root cyst group was significantly higher than that in chronic periapical periodontitis group and control group（P < 0.01）.@*Conclusion@#IL-33 and CD14 positive macrophages increased in normal apical tissue, chronic periapical periodontitis tissue and apical cyst tissue in turn.

T cell immunoglobulin and mucin domain-containing protein 3 inhibits interleukin-12 secretion by CD14+ monocytes from patients with psoriasis vulgaris / 中华皮肤科杂志

Objective To assess the role of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) in regulation of interleukin(IL)-12 secretion by CD14+ peripheral blood monocytes from patients with psoriasis vulgaris.Methods From November 2017 to March 2018,a total of 47 patients with psoriasis vulgaris (psoriasis group) and 19 healthy volunteers (control group) were enrolled from Shanxi Provincial People's Hospital.Peripheral blood mononuclear cells (PBMC) were isolated,and stimulated with Toll-like receptor (TLR) ligands.TIM-3 expression and IL-12 secretion by CD14+ monocytes were measured by flow cytometry.After blockade of TIM-3 pathway by anti-TIM-3 neutralizing antibody,changes in the downstream signaling pathway molecules in and IL-12 secretion by CD14+ monocytes were investigated.Two independent samples t-test was used for comparison between two groups,and Pearson correlation test for correlation analysis.Results Under the unstimulated condition,the level of IL-12 secreted by CD14+ monocytes was very low,and the proportion of CD14+TIM-3+ cells was significantly higher in the psoriasis group (12.20％ ± 2.83％) than in the control group (9.91％ ± 1.77％,t =3.270,P =0.001 7).After the stimulation with TLR ligands,the proportion of CD14+IL-12+ cells was significantly lower in the psoriasis group (13.49％ ± 2.80％) than in the control group (28.97％ ± 8.97％,t =10.71,P ＜0.000 1),but the proportion of CD14+TIM-3+ cells was still higher in the psoriasis group (6.80％ ± 1.11％)than in the control group (4.85％ ± 1.37％,t =6.064,P ＜ 0.000 1).The proportion of CD14+TIM-3+ cells was negatively correlated with that of CD14+IL-12+ cells in both the control group and psoriasis group (r =-0.473,-0.371 respectively,both P ＜ 0.05).The TIM-3 pathway blockade could induce the decrease of suppressor of cytokine signaling 1 in CD14+ monocytes,increase the phosphorylation of signaling transducers and activators of transcription 1,and promote IL-12 secretion by CD 14+ monocytes induced by keratinocytes isolated from psoriatic skin lesions.Conclusion TIM-3 plays a crucial role in the negative regulation of CD 14+ monocyte-induced innate immune response in psoriasis.

Effects of Shenmai injection combined with enteral nutrition on immune function of patients with severe cardiac insufficiency / 中国中西医结合急救杂志

Objective To observe the effect of Shenmai injection combined with enteral nutrition (EN) on immune function in patients with severe cardiac insufficiency. Methods Fifty-seven patients with severe cardiac insufficiency admitted to the Department of Critical Care Medicine of Taizhou Hospital of Zhejiang Province from June 2015 to June 2018 were divided into an EN group (31 cases) and an EN group combined with Shenmai injection group (26 cases). The EN group was given EN on the basis of routine western medicine treatment, while in the EN combined with Shenmai injection group was treated additionally by intravenous drip of Shenmai injection 100 mL/d on the basis of above EN group treatment. The efficacies of the two groups were evaluated after consecutive 7-day treatment in the two groups. The changes in levels of subsets of T-lymphocytes (CD3+, CD4+, CD8+, CD4+/CD8+) and immunosuppressive cells CD14+ monocyte human leukocyte antigen DR (HLA-DR) were observed before and after treatment. Results After treatment, the levels of T-cell subsets CD3+, CD4+, CD4+/CD8+ and CD14+ monocytes HLA-DR in the peripheral blood of the two groups were significantly higher than those before treatment [CD3+: EN group was 0.539±0.126 vs. 0.379±0.093,Shenmai injection group was 0.652±0.185 vs. 0.393±0.091; CD4+: EN group was 0.402±0.121 vs. 0.275±0.066,Shenmai injection group was 0.524±0.168 vs. 0.281±0.077; CD4+/CD8+:EN group was 1.83±0.70 vs. 1.11±0.70,Shenmai injection group was 2.81±0.91 vs. 1.19±0.58; CD14+HLA-DR:EN group was (43.3±7.1)% vs. (35.4±5.7)%,Shenmai injection group was (54.9±6.2)% vs. (36.1±8.3)%]; After treatment, CD8+ in EN group decreased (0.223±0.052 vs. 0.253±0.081), while CD8+ in shenmai injection group increased (0.288±0.051 vs. 0.259±0.078), and the increase degrees of the above-mentioned indexes in EN combined with Shenmai injection group were more obvious than those in the EN group after treatment [CD3+: 0.652±0.185 vs. 0.539±0.126, CD4+: 0.524±0.168 vs. 0.402±0.121, CD8+: 0.288±0.051 vs. 0.223±0.052, CD4+/CD8+: 2.81±0.91 vs. 1.83±0.70, CD14+HLA-DR: (54.9±6.2)%, (43.3±7.1)%, all P < 0.05]. Conclusion The combined use of Shenmai injection and early EN can improve the immune function of T-lymphocytes in patients with severe cardiac insufficiency. The mechanism may be related to the enhancement of the activation of T lymphocytes and promotion of the CD14+ monocytes increase and immune function.

Effect of continuous blood purification on peripheral blood monocyte membrane binding CD14 expression and inflammatory response in patients with traumatic sepsis / 中华创伤杂志

Objective To investigate the effect of continuous blood purification (CBP) on peripheral blood monocyte membrane CD14 (mCD14) expression and inflammatory response in patients with traumatic sepsis Methods A retrospective case control study was conducted on the clinical data of 50 patients with severe sepsis after trauma treated between January 2015 and December 2016. There were 34 males and 16 females, with an average age of 45.37 years (range, 16-73 years). Patients were divided into CBP group (25 cases) and non-CBP group (25 cases) according to whether they agreed to receive CBP treatment. The peripheral blood samples were collected at 0, 12, 24, 48, and 72 hours after treatment, and the mCD14 and leukocyte elastase (HLE) expressions were detected by flow cytometry and by ELISA, respectively. The peripheral blood mononuclear cells were isolated from the two groups 24 h after treatment and cultured in vitro. The variations of mCD14 expression in mononuclear cells were measured at 4, 8, 12, 24, 48, and 72 h after stimulation with lipopolysaccharide (LPS). The expression levels of tumor necrosis factor (TNF) -a, interleukin (IL) -6, and IL-10 in mononuclear cells were detected by ELISA. Results At 12, 24, 48, and 72 hours after treatment, the leukocyte elastase levels in the two groups were lower than those before treatment (P ＜ 0.01), and the decrease in CBP group was significantly greater than that of non CBP group(P＜0.01). At 12, 24, 48, and 72 hours after treatment, the mCD14 levels in both groups were up-regulated before treatment (P ＜0.01), and the increase in CBP group was significantly greater than that of non CBP group (P ＜ 0.01). The mCD14 expressions before treatment, 4 h after treatment, and 8 h after treatment in CBP group were all higher than those in non CBP group at the same time points. At 4, 8, 12, 24, and 48 hours after the re-stimulation with LPS on the mononuclear cells in both groups, the levels of TNF-α and IL-6 in CBP group were significantly higher than those in non-CBP group (P ＜0.01), and there was no significant difference in IL-10 levels between the two groups (P ＞0.05). Conclusions CBP treatment can increase monocyte mCD14 expressions through eliminating inflammatory factors and pro-inflammatory mediators and reducing HLE directly or indirectly in patients with traumatic sepsis. When the body is stimulated again, its anti-inflammatory response ability is markedly stronger than that of patients who have not received CBP treatment.

Halofuginone ameliorates LPS-induced immune disorder of acute lung injury via CD14/NF-κB pathway / 中国免疫学杂志

Objective:To evaluate the regulatory effectsand underlying mechanism of halofuginone (HF) on lipopolysaccharide (LPS)-induced immune disorder of acute lung injury (ALI) in rat. Methods: Rats were treated with LPS and HF. Subsequently,HE staining was performed for pulmonarypathological lesion,apoptosis bodies were calculated by TUNEL assay,the levels of inflammatory factors were confirmed by ELISA assay and the level of CD14 was measured by flow cytometry. Protein levels were determined by Western blot. Results: Treatment of HF dose-dependently alleviated LPS-induced pulmonary injury and inhibited the formation of apoptosis bodies significantly. Meanwhile,HF notably inhibited inflammation of ALI rats,as demonstrated by decreased IL-1β,IL-6 and IL-18. Furthermore,postconditioning with HF markedly decreased CD14+cells. Moreover,HF dose-dependently attenuated the promotive effects of LPS on CD14,TLR4 and NF-κB p65. Conclusion: HF regulates LPS-induced immune disorder of ALI in rat via CD14/NF-κB pathway.

Relationship of Cell Compositions in Allografts with Outcomes after Haploidentical Transplantation for Acquired Severe Aplastic Anemia: Effects of CD34 and CD14 Cell Doses / 中华医学杂志(英文版)

<p><b>Background</b>The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA).</p><p><b>Methods</b>A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis.</p><p><b>Results</b>A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124-4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14 (P = 0.018) and CD34 cells (P < 0.001) were associated with a successful platelet engraftment. A successful platelet was associated with superior survival (P < 0.001). No correlation of other cell components with outcomes was observed.</p><p><b>Conclusions</b>These results provide evidence and explain that higher doses of CD34 and CD14 cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.</p>

Immune development in HIV-exposed uninfected children born to HIV-infected women

ABSTRACT Immunological and clinical findings suggestive of some immune dysfunction have been reported among HIV-exposed uninfected (HEU) children and adolescents. Whether these defects are persistent or transitory is still unknown. HEU pediatric population at birth, 12 months, 6-12 years were evaluated in comparison to healthy age-matched HIV-unexposed controls. Plasma levels of LPS, sCD14, cytokines, lymphocyte immunophenotyping and T-cell receptor excision circles (TREC) were assessed. HEU and controls had similar LPS levels, which remained low from birth to 6-12 years; for plasma sCD14, IL-2, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17, IFN-γ, TNF-α, G-CSF, GM-CSF and MCP-1, which increased from birth to 12 months and then decreased at 6-12 years; and for TREC/106 PBMC at birth in HEU and controls. By contrast, plasma MIP-1β levels were lower in HEU than in controls (p=0.009) at 12 months, and IL-4 levels were higher in HEU than controls (p=0.04) at 6-12 years. Immune activation was higher in HEU at 12 months and at 6-12 years than controls based on frequencies of CD38+HLA-DR+CD8+T cells (p=0.05) and of CD38+HLA-DR+CD4+T cells (p=0.006). Resting memory and activated mature B cells increased from birth to 6-12 years in both groups. The development of the immune system in vertically HEU individuals is comparable to the general population in most parameters, but subtle or transient differences exist. Their role in influencing clinical incidences in HEU is unknown.

Desempeño de la presepsina como biomarcador temprano de sepsis en un hospital de alta complejidad en Medellín, Colombia / Performance of presepsin as early biomarker of sepsis in a high complexity hospital from Medellin, Colombia

Introducción: la presepsina es el subtipo soluble de la glicoproteína CD14 expresada en la superficie de membrana de los monocitos y los macrófagos; molécula importante en el proceso inflamatorio. Varios estudios sugieren realizar su medición para la identificación temprana de la sepsis. Objetivo: determinar el desempeño diagnóstico y pronóstico de la presepsina en pacientes con sepsis clínica de un hospital de alta complejidad en Medellín, Colombia. Materiales y métodos: se realizó un estudio descriptivo prospectivo de cohorte única en 60 pacientes con diagnóstico de sepsis clínica durante marzo y diciembre de 2012. La presepsina se midió al momento del diagnóstico, a las 24 y 72 horas; la proteína C reactiva, la procalcitonina y el hemocultivo sólo al momento del diagnóstico. Se utilizaron herramientas de estadística descriptiva para la caracterización de la población y análisis bivariado para la comparación entre medianas. Resultados: El 98,3% de los pacientes tuvieron valores de presepsina sugestivos de sepsis, observándose un valor significativamente más alto en los pacientes sin mejoría (mayor que 700 pg/mL). Se observaron valores de presepsina mayores que 1.000 pg/mL a las 0 y 72 horas del diagnóstico en los pacientes que murieron, pero no se observaron diferencias significativas en comparación con los que no murieron. La proteína C reactiva y la procalcitonina mostraron valores aumentados en la mayoría de los pacientes. Conclusiones: los hallazgos de este estudio se relacionan con lo encontrado en otros estudios donde concluyen que la presepsina es un buen marcador de sepsis, con un importante valor pronóstico y mayor especificidad que otros biomarcadores tradicionales. Palabras clave: sepsis, biomarcadores, diagnóstico, antígenos CD14. (AU)

Introduction: Presepsin is the soluble form of CD14 molecule, a glycoprotein expressed on the membrane surface of monocytes and macrophages and important to inflammatory response. Several studies suggest that presepsin measuring could be used as a good tool to early sepsis diagnosis. Objective: To determine the diagnostic and prognostic performance of presepsin in patients with clinical sepsis at a high complexity hospital from Medellin, Colombia. Materials and methods: A prospective, descriptive cohort study was performed in 60 patients diagnosed with clinical sepsis between March and December of 2012. Presepsin measurement was made at diagnosis time and after 24 and 72 hours. Blood culture, C-reactive protein and procalcitonin were also measured but only at the diagnosis time. Results: 98.3% of patients had presepsin values suggestive of sepsis, with a significantly higher value in patients without clinical improvement (greater than 700 pg/mL). Presepsin values greater than 1,000 pg /mL at 0 and 72 hours of diagnosis was obtained in patients who died, but no significant differences compared to those who did not die were observed. C-reactive protein and procalcitonin showed increased values in most patients. Conclusions: The findings of this study are related to others where it is concluded that presepsin is a good marker of sepsis with an important prognostic value and greater specificity than other traditional biomarkers. (AU)

Curative effect of paraquat detoxification recipe combined with continuous hemoperfusion in the treatment of patients with APP and clinical value of Presepsin / 中华危重病急救医学

Objective To investigate the clinical effect of paraquat (PQ) detoxification recipe combined with continuous hemoperfusion (HP) in the treatment of patients with acute paraquat poisoning (APP) and clinical significance of soluble CD14 subtype (sCD14-st, Presepsin). Methods A prospective randomized controlled trial was conducted. 152 patients with moderate APP admitted to Department of Emergency Medicine of Harrison International Peace Hospital Affiliated to Hebei Medical University from July 2013 to June 2017 were enrolled, and they were randomly divided into three groups. The patients in HP group (group A, n = 35) only received 2-hour HP for 3 times, 8 hours each time, those in PQ detoxification recipe combined with HP group (group B, n = 50) received PQ detoxification recipe 1 (once per 2 hours until no PQ component was found in faeces) and 2 (3 times a day for 14 days) beside HP. The others in PQ detoxification recipe combined with persistent HP group (group C, n = 67) received continuous HP until the PQ component in serum was not detected. The parameters of organ function and inflammatory factor, and blood Presepsin and PQ contents were determined before and after treatment. The curative effect and 28-day mortality were recorded. The correlations between serum Presepsin level and PQ content as well as 28-day mortality were analyzed with Pearson correlation analysis. Receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of Presepsin on prognosis. Results The total effective rate of group C was significantly higher than that of groups A and B [70.1% (47/67) vs. 34.3% (12/35), 54.0% (27/50)], and 28-day mortality was significantly lowered [29.8% (20/67) vs. 65.7% (23/35), 46.0% (23/50), both P < 0.05]. There was no significant difference in alanine aminotransferase (ALT), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukins (IL-6 and IL-10) before treatment among the three groups. Five days after treatment, the above parameters in the three groups were increased as compared with those before treatment, but the increase degree in group C was the lowest. At 7 days after treatment, the parameters were decreased, especially in group C. There was no significant difference in serum Presepsin and PQ levels before treatment among the three groups. With the prolongation of treatment time, the Prespsin levels in groups A, B, and C were increased, and peaked at 12 hours (μg/L: 4.28±0.20, 3.87±0.25, 3.53±0.23), then gradually decreased,and the PQ contents were lower than those before treatment from 8 hours (mg/L: 1.76±0.12 vs. 2.12±0.17, 1.57±0.08 vs. 2.24±0.16, 1.25±0.10 vs. 2.14±0.18), with a time dependence pattern, especially in group C (all P < 0.05) . Correlation analysis showed that blood Presepsin level was positively correlated with PQ content and 28-day mortality (r1= 0.917, r2= 0.864, both P = 0.001), suggesting that the higher the PQ content was, the higher the Presepsin level, and the higher the 28-day mortality was. ROC curve analysis showed that the area under ROC curve (AUC) of Presepsin predicting 28-day mortality was 0.863; when the cut-off value was 1.22 μg/L, the sensitivity was 83.3%, the specificity was 81.4%, the positive predictive value was 77.46%, and the negative predictive value was 86.42%. Conclusions Early administration of PQ detoxification recipe combined with continuous HP treatment can effectively reduce Presepsin level, decrease the mortality of patients with moderate APP, improve the prognosis. Presepsin can assess the prognosis of patients with APP.