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Significance Of Procalcitonin,C-reactive Protein In Fever And Loss Of Reelin Suppresses Cell Survival And Mobility In Non-hodgkin Lymphoma

Posted on:2019-04-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z L WangFull Text:PDF
GTID:1364330545959010Subject:Clinical medicine
Abstract/Summary:PDF Full Text Request
Objective Fever is a common symptom we can often see in clinical works.The normal human body can maintain a constant body temperature through the hypothalamus thermoregulatory center control.Various factors can lead to the central body temperature regulation dysfunction,resulting in excessive heat.If the temperature rises above the normal range,fever occurs.Fever can be caused by thermal factors and non pyrogen factors.Since the causes of fever are complex,early diagnosis is quite difficult.So,finding a simple,easy way is very important.In our study,by determination of procalcitonin(PCT),C-reactive protein(CRP),and ferritin(Ferr)expression in patients with fever,we want to clarify their meanings in eraly diagnosis.By doing all this,we want to provide the basis for the early diagnosis of fever,so that we can know more about the cause of the disease and the application of antibiotics.Methods Inpatients who had fever during Jan 1st,2016 to Dec 31st,2016 are included in our study.If the tempreture is above 38?,we say he/she has fever.Then,we test their CRP,PCT and Ferr levels,and we detect the WBC at the same time.If possible,we take blood culture,G/GM test also.After gathering all the data,we use SPSS 22.0 software to analyze.The steps are as follows:first,by infected or not,we grouped the patients into 2 groups,and we compared the differences between them;second,in each group,according to the levels of WBC,we divided the patients into 4 sub-groups(WBC<1.0×109/L?WBC 1.0?3.5×109/L?WBC 3.5?10×109/L?WBC>10×109/L),still we compared the difference;third,draw ROC curves according to CRP>10mg/L,PCT>0.5 ng/ml and Ferr>336.2ng/ml;then we draw ROC curve by CRP>10mg/L+PCT>0.5 ng/ml+ Ferr>336.2ng/ml,so that we can spectulate the values in diagnosis of fever.Since the outcomes of CRP,PCT and Ferr are all according with normal distribution,we use F test to evaluate.In all analysis,we think P<0.05 means have statistical significance.Results In our study,we have a total data of 317 cases,in which 12 cases are deleted due to lack of some data.In the end,305 were included in the analysis.The minimum age is 14 years old,while the maximum age is 83 years old,the median age was 56.We have 136 male and 169 female patients,the ratio between male and female is 136:169.The results showed that in the infection group,the CRP,PCT,Ferr were significantly higher,and the difference makes statistical signifance.In the four sub-groups according to the WBC levels in each group,the outcomes are as follows.In infection group,the differences of CRP and Ferr have statistical significance.CRP level is highest in sub-group in which WBC>10.0 × 109/L,and lowest in sub-group while WBC is below 1.0 × 109/L;but Ferr level is highest in sub-group while WBC<1.0 × 109/L,and in the left three sub-groups,Ferr didn't have differnences.While in the non-infection group,the levels of CRP also have differences.In sub-group in which WBC<1.0 × 109/L,CRP is 111.35mg/l.But when WBC is between 3.5 to 10 X 109/L,CRP level drops to 26.67mg/L,then CRP begins to rise.But we didn't detect differnences of PCT and Ferr in non-infection group.While drowing ROC curves to speculaing infection,we find that the sensitivity of CRP is 86.16%,the specificity is 26.87%,the positive predictive value of infection is 79.75%,the negative predictive value of infection is 36.73%;as to PCT,the sensitivity is 98.15%,the specificity is 19.27%,the positive predictive value of infection is 25.48%,the negative predictive value of infection is 97.37%.In case of Ferr,the sensitivity is 81.58%,the specificity is 13.11%,the positive predictive value of infection is 70.46%,the negative predictive value of infection is 22.22%.In patients whose WBC is below 1.0 × 109/L,the sensitivity of CRP is 87.77%,the positive predictive value of infection is 90.63%;and the sensitivity,positive and negative predictive value of PCT are all 100%;the sensitivity of Ferr is 91.30%,the positive predictive value of infection is 91,30%.Conclusions In patients with fever,the levels of PCT,CRP and Ferr are all significantly increased,and the difference between infection and noninfection groups is statistically significant.In patients who have icfection,the differences of CRP and Ferr are statistically significant in the 4 sub-groups divided by the levels of WBC.CRP level is highest in sub-group in which WBC is above 10.0 × 109/L,and lowest in sub-group while WBC is below 1.0 × 109/L;and Ferr level is highest in sub-group while WBC is below 1.0 × 109/L,and in the left three sub-groups,we didn't see differnences of Ferr.In the non-infection group,the levels of CRP also have differences.In sub-group in which WBC<1.0 × 109/L,CRP is 111.35mg/l.But when WBC is between 3.5 to 10 × 109/L,CRP level drops to 26.67mg/L,then CRP begins to rise.But we didn't detect differnences of PCT and Ferr in non-infection group.So we infer that CRP,PCT can be used as ideal early diagnosing indexs of infection,Combinatin of CRP,PCT and ferritin has good predictive value for infection.Objective Non-Hodgkin lymphoma(NHL)is thought as the most common hematologic malignancy arising from lymphatic cells worldwide.Approximately 90%of lymphoma patients have non-Hodgkin lymphoma(NHL).NHL often arises from genetic alterations such as gene translocations.It has been found that translocation of MYC oncogene on chromosome 8 with IGH gene on chr14,22 or 2 in adolescents Burkitt lymphoma patients.Several checkpoint inhibitors are used for immune checkpoint blockade and other immune therapies such as pidilizumab,nivolumab and pembrolizumab.These reports still are not enough to explain the pathogenesis of NHL.Reelin,is a secreted glycoprotein.Previous studies of Reelin mostly focused on its functions in nervous system development.However,it was recently demonstrated to be involved in the pathogenesis of cancer.Studies show that Reelin has very important role in the control of cell migration.In vitro and in vivo,Reelin protein can both promote the proliferation of tumor cells,and the Warburg effect is enhanced in Reelin expressing cells.But its oncogenic activities in non-Hodgkin lymphoma(NHL)remain unclear.Therefore,we carried out this study,so that we can evaluate the functional role of Reelin in NHL,clarify the underlying molecular mechanisms.Methods In the present study,we analyzed Reelin expression in lymphoma tissues and cell lines using immunohistochemistry,immunofluorescence staining,qRT-PCR and Western blotting.Then,the expression of Reelin was silenced with short hairpin RNA(shRNA)-expressing plasmid in the NHL cell line A20.The effects of Reelin depletion on cell growth,migration and invasion in vitro were determined by CCK-8 and transwell assays.Flow cytometry was used to examine the cell cycle status and cellular apoptosis.Hoechst 33258 fluorescence staining was used to analyze morphologic changes caused by apoptosis.The second messenger,cAMP was analyzed by ELISA.In addition,we used nude mice to evaluate the tumori-genic ability of Reelin.Results Aberrant upregulated levels of mRNA and protein of Reelin were observed in lymphoma tissues and cell lines.Knockdown of Reelin suppressed lymphoma growth,migration and invasion ability of A20.Furthermore,Reelin depletion induced cell cycle arrest in G0/G1 phase and promoted apoptosis of A20 cells.Further analysis indicated that knockdown of Reelin downregulated the expression of CDK5 and IL-10 and activated caspase-3 in shReelin group.ELISA assay showed cAMP at a lower level in shReelin group.SQ22536,a cAMP pathway inhibitor,treated A20 cells and revealed likely effects.The tumor size in a mouse model injected shReelin was significantly smaller than controls.Conclusions These results suggest that Reelin played essential roles in the development of lymphoma and might be a potential drug target in lymphoma.
Keywords/Search Tags:procalcitonin(PCT), C-reactive protein(CRP), ferritin(Ferr), fever, infection, lymphoma, Reelin, proliferation, apoptosis, cAMP
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