Diagnostic significance of serum levels of serum amyloid A,procalcitonin,and high-mobility group box 1 in identifying necrotising enterocolitis in newborns

BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.

Serum Amyloid A Protein: A Potential Biomarker Correlated With Clinical Stage of Lung Cancer

Objective To identify serum diagnosis or progression biomarkers in patients with lung cancer using protein chip profiling analysis. Method Profiling analysis was performed on 450 sera collected from 213 patients with lung cancer, 19 with pneumonia, 16 with pulmonary tuberculosis, 65 with laryngeal carcinoma, 55 with laryngopharyngeal carcinoma patients, and 82 normal individuals. A new strategy was developed to identify the biomarkers on chip by trypsin pre-digestion. Results Profiling analysis demonstrated that an 11.6kDa protein was significandy elevated in lung cancer patients, compared with the control groups （P〈0.001）. The level and percentage of 11.6kDa protein progressively increased with the clinical stages Ⅰ-Ⅳ and were also higher in patients with squamous cell carcinoma than in other subtypes. This biomarker could be decreased after operation or chemotherapy. On the other hand, 11.6kDa protein was also increased in 50% benign diseases of lung and 13% of other cancer controls. After trypsin pre-digestion, a set of new peptide biomarkers was noticed to appear only in the samples containing a 11.6kDa peak. Further identification showed that 2177Da was a fragment of serum amyloid A （SAA, MW 11.6kDa）. Two of the new peaks, 1550Da and 1611Da, were defined from the same protein by database searching. This result was further confirmed by partial purification of 11.6kDa protein and MS analysis. Conclusion SAA is a useful biomarker to monitor the progression of lung cancer and can directly identify some biomarkers on chip.

Decrease in Serum Amyloid a Protein Levels Following Three-month Stays in Negatively Charged Particle-dominant Indoor Air Conditions

Objective The changes in serum adipokines and cytokines related to oxidative stress were examined during 3 months ‘Off to On’ and ‘On to Off’ periods using negatively charged particle-dominant indoor air conditions（NCPDIAC）.Methods Seven volunteers participated in the study,which included ‘OFF to 3 months ON’ periods（ON trials） for a total of 16 times,and ‘ON to 3 months OFF’（OFF trials） periods for a total of 13 times.Results With the exception of one case,serum amyloid A（SAA） levels decreased significantly during the ON trials.Conclusion Considering that SAA is an acute phase reactive protein such as C reactive protein（CRP）,this observed decrease might indicate the prevention of cardiovascular and atherosclerotic changes,since an increase in high-sensitive CRP is associated with the subsequent detection of these events.

Immune infiltration-associated serum amyloid A1 predicts favorable prognosis for hepatocellular carcinoma

BACKGROUND Serum amyloid A1(SAA1)is an acute-phase protein involved in acute or chronic hepatitis.Its function is still controversial.In addition,the effect of the expression of SAA1 and its molecular function on the progression in hepatocellular carcinoma(HCC)is still unclear.AIM To demonstrate the expression of SAA1 and its effect on the prognosis in HCC and explain further the correlation of SAA1 and immunity pathways.METHODS SAA1 expression in HCC was conducted with The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC)in GEPIA tool,and the survival analysis based on the SAA1 expression level was achieved in the Kaplan-Meier portal.The high or low expression group was then drawn based on the median level of SAA1 expression.The correlation of SAA1 and the clinical features were conducted in the UALCAN web-based portal with TCGA-LIHC,including tumor grade,patient disease stage,and the TP53 mutation.The correlation analysis between SAA1 expression and TP53 mutation was subjected to the TCGA portal.The tumor purity score and the immune score were analyzed with CIBERSORT.The correlation of SAA1 expression and tumor-infiltrating lymphocytes was achieved in TISIDB web-based integrated repository portal for tumor-immune system interactions.GSE125336 dataset was used to test the SAA1 expression in the responsive or resistant group with anti-PD1 therapy.Gene set enrichment analysis was applied to evaluate the gene enrichment signaling pathway in HCC.The similar genes of SAA1 in HCC were identified in GEPIA,and the proteinprotein interaction of SAA1 was conducted in the Metascape tool.The expression of C-X-C motif chemokine ligand 2,C-C motif chemokine ligand 23,and complement C5a receptor 1 was studied and overall survival analysis in HCC was conducted in GEPIA and Kaplan-Meier portal,respectively.RESULTS SAA1 expression was decreased in HCC,and lower SAA1 expression predicted poorer overall survival,progression-free survival,and disease-specific survival.Furthermore,SAA1 expression was further decreased with increased tumor grade and patient disease stage.Also,SAA1 expression was further downregulated in patients with TP53 mutation compared with patients with wild type TP53.SAA1 expression was negatively correlated with the TP53 mutation.Lower SAA1 predicted poorer survival rate,especially in the patients with no hepatitis virus infection,other than those with hepatitis virus infection.Moreover,the SAA1 expression was negatively correlated with tumor purity.In contrast,SAA1 expression was positively correlated with the immune score in HCC,and the correlation analysis between SAA1 expression and tumor-infiltrating lymphocytes also showed a positive correlation in HCC.Decreased SAA1 was closely associated with the immune tolerance of HCC.C-X-C motif chemokine ligand 2 and C-C motif chemokine ligand 23 genes were identified as the hub genes associated with SAA1,which could also serve as favorable prognosis markers for HCC.CONCLUSION SAA1 is downregulated in the liver tumor,and it is closely involved in the progression of HCC.Lower SAA1 expression indicates lower survival rate,especially for those patients without hepatitis virus infection.Lower SAA1 expression also suggests lower immune infiltrating cells,especially for those with immune cells exerting anti-tumor immune function.SAA1 expression is closely associated with the anti-tumor immune pathways.

Serum amyloid A and pairing formyl peptide receptor 2 are expressed in corneas and involved in inflammation-mediated neovascularization

AIM:To solidify the involvement of Saa-related pathway in corneal neovascularization(CorNV).The pathogenesis of inflammatory CorNV is not fully understood yet,and our previous study implicated that serum amyloid A(Saa)1(Saa1)and Saa3 were among the genes up-regulated upon CorNV induction in mice.METHODS:Microarray data obtained during our profiling project on CorNV were analyzed for the genes encoding the four SAA family members(Saa1-4),six reported SAA receptors(formyl peptide receptor 2,Tlr2,Tlr4,Cd36,Scarb1,P2rx7)and seven matrix metallopeptidases(Mmp)1a,1b,2,3,9,10,13reportedly to be expressed upon SAA pathway activation.The baseline expression or changes of interested genes were further confirmed in animals with CorNV using molecular or histological methods.CorNV was induced in Balb/c and C57BL/6 mice by placing either three interrupted 10-0 sutures or a 2 mm filter paper soaked with sodium hydroxide in the central area of the cornea.At desired time points,the corneas were harvested for histology examination or for extraction of mRNA and protein.The mRNA levels of Saa1,Saa3,Fpr2,Mmp2and Mmp3 in corneas were detected using quantitative reverse transcription-PCR,and SAA3 protein in tissues detected using immunohistochemistry or western blotting.RESULTS:Microarray data analysis revealed that Saa1,Saa3,Fpr2,Mmp2,Mmp3 messengers were readily detected in normal corneas and significantly upregulated upon CorNV induction.The changes of these five genes were confirmed with real-time PCR assay.Onthe contrary,other SAA members(Saa2,Saa4),other SAA receptors(Tlr2,Tlr4,Cd36,P2rx7,etc),or other Mmps(Mmp1a,Mmp1b,Mmp9,Mmp10,Mmp13)did not show consistent changes.Immunohistochemistry study and western blotting further confirmed the expression of SAA3 products in normal corneas as well as their upregulation in corneas with CorNV.CONCLUSION:SAA-FPR2 pathway composing genes were expressed in normal murine corneas and,upon inflammatory stimuli challenge to the corneas,their expressions were up-regulated,suggesting their roles in pathogenesis of CorNV.The potential usefulness of SAA-FPR2 targets in future management of CorNVrelated diseases deserves investigation.

Roles of Serum Amyloid A 1 Protein Isoforms in Rheumatoid Arthritis

Secondary amyloid A amyloidosis,a lethal complication,is induced when acute or chronic infection coexists with over-secretion of the serum amyloid A 1(SAA1)protein and deposition in key internal organs.Previously,using the whole-exome sequencing method,we identified a novel deleterious mutation SAA1.2 in rheumatoid arthritis(RA)patients.However,the role of SAA1 in RA pathogenesis and its complications remains unknown.The purpose of this study was to determine the pathogenetic roles of SAA1 protein isoforms in RA progression.We modified an experimental adenovirus infection protocol to introduce SAA1.2 gene alleles into the knee joints of mice and used SAA1.3 and SAA1.5 as controls.Microcomputed tomography analysis was applied to determine changes in bone morphology and density.Immunohistochemical(IHC)analysis,flow cytometry,enzyme-linked immunosorbent assay(ELISA),and real-time polymerase chain reaction(RT-PCR)were used to investigate disease progression and cytokine alterations in the course of adenoviral SAA-induced knee joint inflammation and bone destruction.We found that the arthritis-inducing effect of SAA1.2 transcription in the knee joints and mutant SAA1 protein secretion in blood resulted in the stimulation of immune responses,leading to CD8^(+)T cell and pro-inflammatory cytokine elevation,such as interleukin(IL)-6,IL-22,matrix metalloproteinase(MMP)-3,MMP-9,with subsequent synovial inflammation and bone destruction.These findings indicate that SAA1 protein isoforms,particularly SAA1.2,play a significant role in the induction and progression of RA and may have potential value in the early diagnosis and severity prediction of RA.

Comparative evaluation of acute phase proteins by C-reactive protein(CRP)and serum amyloid A(SAA)in nonhuman primates and feline carnivores

The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals.

Association of SelS mRNA expression in omental adipose tissue with Homa-IR and serum amyloid A in patients with type 2 diabetes mellitus

Background Tanis was reported as a putative receptor for serum amyloid A （SAA） involving glucose regulated protein in insulin regulated resistance. It was found to be dysregulated in diabetic rats （Psammomys obesus, Israeli sand rat） and its homologue for humans is SelS/AD-015. The present study analyzed mRNA expression of SelS in omental adipose tissue biopsies from patients with type 2 diabetes mellitus （T2DM）, and age- and weight-matched nondiabetic patients, the relationship of SelS mRNA with Homa-IR and serum SAA level. Methods Human omental adipose tissues from ten cases of type 2 diabetic patients and twelve cases of nondiabetic individuals were analyzed for the expression level of SelS mRNA by semiquantitative polymerase chain reaction （PCR）, Homa-IR estimated by standard formula and SAA level by enzyme-linked immunosorbent assay （ELISA）. Results SelS mRNA expression, Homa-IR and serum SAA were higher in T2DM sufferers than in nondiabetic control group. SelS mRNA level was positively correlated with Homa-IR and SAA level in each group. Conclusions SelS protein may be involved in insulin resistance in Chinese with T2DM by acting as the SAA receptor, thus playing an important role in the development of T2DM and atherosclerosis.

High-density lipoprotein associated factors apoA-I and serum amyloid A in Chinese non-diabetic patients with coronary heart disease

Background High-density lipoprotein cholesterol（HDL-C）levels are a strong,independent inverse predictor of coronary heart disease （CHD）.In this cross-sectional study we investigated the interrelationships between HDL-C and HDL relaled factors apolipoprotein A-I（apoA-I）and serum amyloid A（SAA）and the presence and extent of CHD in a population of Chinese patients with CHD. Methods Two hundred and twenty-four consecutive patients took part in this study.Demographic data were obtained from hospital records.Serum chemical concentrations were measured by standard laboratory methods.Reaults The concentrations of high-sensitive C-reactive protein（hsCRP）（median：1.85 mg/L）and SAP,（median：9.40 mg/L）were significantly higher in the CHD group（P〈0.05）,while concentrations of HDL-C（0.03±0.25）mmol/L）and apoA-I（（604.59±1 05.79）mmol/L）were significantly lower than those in the non-CHD group（P〈0.05）.The concentrations of apoA-l decreased with the increase in vascular damage.but the difference did not reach statistical significance.However, the concentrations of hsCRP and SAA increased with the increase in vascular damage.The unadjusted odd ratios（ORs）（CI） for apoA-I and SAA of the presence of CHD were 0.093（0.990-0.997）（P=0.00）and 2.571（1.029-6.424）（P〈0.05）,respectively.The association between elevated SAA and the presence of CHD was lost after adjusting for lipid status parameter concentrations.The associations between apoA-I.SAA and the extent of CHD remained strong,regardless of confounding variables.Conclusions Increased concentrations of SAA represent the inflammatory marker of the extent of coronary stenosis in patients with CHD.In contrast to SAA, the level of apoA-I was also associated with the presence of CHD, indicating that apoA-I was not only a marker of CHD presence but also a quantitative indicator of CHD extent.In short.determining the change apolipoprotein content within HDL particle is a more accurate and effective method to evaluate the impact of HDL on CHD.

The relationship between serum amyloid A and apolipoprotein A-I in high-density lipoprotein isolated from patients with coronary heart disease

Background Alteration in the protein composition of high-density lipoprotein （HDL） has been proposed as a mechanism for the development of coronary heart disease （CHD）.In HDL,an increase in serum amyloid A protein （SAA） accompanying the decrease in apolipoprotein A-I （apoA-I） has been found during the acute inflammation period.However,whether this phenomenon persists in CHD patients,a disease related to inflammation,is unknown.The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients.Methods Overall,98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study.Potassium bromide （KBr） density gradient ultracentrifugation was used to isolate HDL from plasma.The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits.Pearson＇s correlation and general linear models were used in the analysis.Results Compared with controls,patients with CHD had a significant decrease in the amount of apoA-I （（14.21±8.44） μg/ml vs.（10.95±5.95） μg/ml,P =0.003） in HDL and a significant increase in the amount of log SAA （1.21±0.46 vs.1.51±0.55,P 〈0.00001）.Differences were independent of age,body mass index （BMI）,HDL cholesterol （HDL-C）,and other factors.An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group （β =2.0,P =0.026）.In the general linear model,changes in Iog（SAA）,age,age2,gender,BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I.Conclusions This study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients,indicating the alteration of protein composition in HDL.However,the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.

Effects of five-year intensive multifactorial intervention on the serum amyloid A and macroangiopathy in patients with short-duration type 2 diabetes meUitus

Background A five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A （SAA） levels and the incidence of atherosclerosis （AS） in patients with short-duration type 2 diabetes mellitus （T2DM） without macroangiopathy, and whether intensive multifactorial intervention could prevent or at least postpone the occurence of macroangiopathy. Methods Among 150 patients with short-duration T2DM, 75 were assigned to receive conventional outpatient treatment （conventional group） and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia, hypertension, dyslipidemia and received aspirin simultaneously （intensive group）. Results Plasma SAA levels were higher in diabetic patients than those in healthy control subjects, and decreased obviously after intensive multifactorial intervention. The levels of SAA were positively correlated with body mass index （BMI）, waist hip ratio （WHR）, triglyceride （TG）, high sensitive C-reactive protein （hs-CRP） and common carotid intima-media thickness （CC-IMT）. The standard-reaching rates of glycemia, blood pressure and lipidemia were significantly higher in intensive group than those of conventional group. The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group. Conclusions Intensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM. SAA might be one of the risk factors of T2DM combined with AS.

Discovery and identification of Serum Amyloid A protein elevated in lung cancer serum

Two hundred and eighteen serum samples from 175 lung cancer patients and 43 healthy individuals were analyzed by using Surface Enhaced Laser Desorption/Ionization Time of Flight Mass Spectrome- try (SELDI-TOF-MS). The data analyzed by both Biomarker Wizard? and Biomarker Patterns? software showed that a protein peak with the molecular weight of 11.6 kDa significantly increased in lung cancer. Meanwhile,the level of this biomarker was progressively increased with the clinical stages of lung cancer. The candidate biomarker was then obtained from tricine one-dimensional sodium dodecyl sul- fate-polyacrylamide gel electrophoresis by matching the molecular weight with peaks on WCX2 chips and was identified as Serum Amyloid A protein (SAA) by MALDI/MS-MS and database searching. It was further validated in the same serum samples by immunoprecipitation with commercial SAA antibody. To confirm the SAA differential expression in lung cancer patients, the same set of serum samples was measured by ELISA assay. The result showed that at the cutoff point 0.446(OD value)on the Receiver Operating Characteristic (ROC) curve, SAA could better discriminate lung cancer from healthy indi- viduals with sensitivity of 84.1% and specificity of 80%. These findings demonstrated that SAA could be characterized as a biomarker related to pathological stages of lung cancer.

The diagnostic value of transient elastography combined with serum SAA and IL-6 in the degree of hepatitis B liver fibrosis

Objective:To investigat the diagnostic value of transient elastography combined with serum amyloid A and interleukin-6 in the degree of hepatitis B liver fibrosis.Methods:A total of 334 patients with chronic HBV infection that were admitted to the Department of Infectious Diseases of the First Affiliated Hospital of Hainan Medical College from January 2020 to May 2022 with informed consent and underwent liver biopsy puncture were selected.According to the pathological results,they were divided into no obvious fibrosis group,obvious fibrosis group and liver cirrhosis group.Comparison of liver stiffness measurement(LSM),serum amyloid A(SAA0,IL-6 levels between different groups.This study drawed was conducted draw the receiver operating characteristic(ROC)curve of each index to diagnose significant liver fibrosis and liver cirrhosis,and compared the area under the ROC curve(AUC)and diagnostic efficacy of each non-invasive fibrosis diagnostic model.The diagnostic performance of the combined assay was superior to that of APRI and FIB-4 In different degrees of liver fibrosis.Results:According to the degree of liver fibrosis,the levels of SAA,IL-6,and LSM in the no significant fibrosis group(n=140),the significant fibrosis group(n=134),and the cirrhosis group(n=60)were statistically significant difference(All P<0.001).SAA,IL-6 and LSM were significantly correlated with the degree of liver fibrosis(rs=0.456,rs=0.482,rs=0.602,All P<0.001).The AUC of SAA and IL-6 for the diagnosis of significant fibrosis in hepatitis B were 0.738 and 0.809,respectively.And the AUC for the diagnosis of liver cirrhosis were 0.813 and 0.823,respectively.The AUC for the combined diagnosis of significant fibrosis and cirrhosis were 0.930 and 0.964,respectively.The diagnostic performance of the combined assay was superior to that of APRI and FIB-4 in different degrees of liver fibrosis(All P<0.001).Conclusion:LSM combined with serum SAA and IL-6 has great diagnostic value for different degrees of hepatitis B liver fibrosis.

Role of biomarkers in community-acquired pneumonia management

Community-acquired pneumonia(CAP)poses a significant global health threat,particularly affecting vulnerable populations.Biomarkers and scoring systems play a crucial role in diagnosing,assessing severity,and guiding treatment decisions for CAP patients.Biomarkers like C reactive protein,procalcitonin,and the neutrophil-to-lymphocyte ratio aid in diagnosis and severity assessment,while scoring systems such as CURB-65 and Pneumonia Severity Index classify patients into risk categories.Emerging biomarkers(uremia,elevated respiratory rate,hypotension,and age≥65)like serum amyloid A and S100 proteins show promise in predicting disease severity and prognosis.However,further research is needed to determine their precise roles and clinical utility in CAP management.

血清淀粉样蛋白A的检测方法及临床应用研究进展

血清淀粉样蛋白A(Serum Amyloid A,SAA)是一种急性期炎症反应蛋白,可作为炎症和肿瘤的生物标志物之一。近年来,SAA在感染性疾病的诊断和预防方面得到了广泛应用,但很少有研究对SAA检测方法及临床应用进行系统的综述。因此,本文对SAA的主要检测方法及临床应用进行了概括,以期为相关科研工作者进一步深入研究SAA提供参考和借鉴。

Serum Markers of Systemic Inflammation in Patients with Pulmonary Tuberculosis

Serum markers of systemic inflammation （SAA （serum amyloid protein A）, CRP （C-reactive protein）, cq-AT （ct l-antitripsin）, Hp （haptoglobin） and F （fibrinogen）） have been studied in 317 patients with pulmonary tuberculosis. It was established that sensitivity of SAA as an activity marker was higher than of other acute phase reactants, because its levels were increased in 98.8% patients, whereas the level of CRP exceeded the norm in 80.8%, α1-AT--in 59.3%, Hp----in 43.5% and F--in 63.1% cases. The degree of increase of acute phase reactants directly related to the expressiveness of tuberculosis intoxication, the extent of the process in the lung and the quantity of MTB （M. tuberculosis） in sputum. We concluded that SAA was a useful marker of the process activity in patients with pulmonary tuberculosis and its sensitivity was higher than that of other acute phase reactants.

Ischemic stroke susceptibility gene in a Northern Han Chinese population

Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the –607C allele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affiliated Hospital of Qingdao University Medical College, China, and 226 healthy controls. Both patients and controls were from the Han population in northern China. Immunoresonance scattering assays detected increased serum amyloid A protein, C-reactive protein, and interleukin-18 levels in ischemic cerebrovascular disease patients compared with healthy controls. Analysis of the –607C/A （rs1946518） polymorphism in the interleukin-18 gene promoter showed ischemic cerebrovascular disease patients exhibited increased frequencies of the CC genotype and C alleles than healthy controls. Genotype and allele frequencies of the interleukin-18 –137G/C （rs187238） polymorphism and the –13T/C （rs11024595） polymorphism in the 5＇-flanking region of serum amyloid A, showed no significant difference between the two groups. Multivariate logistic regression analysis on the interleukin-18 promoter A/C genetic locus, for correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and an ischemic stroke family history, showed ischemic cerebrovascular disease risk in individuals without the A allele （C homozygotes） was 2.2-fold greater than in A allele carriers. Overall, our findings suggest that the –13T/C （rs11024595） polymorphism in the 5′-flanking region of serum amyloid A has no correlation with ischemic cerebrovascular disease, but the C allele of the –607C/A （rs1946518） polymorphism in the interleukin-18 promoter is a high-risk factor for ischemic cerebrovascular disease in the Han population of northern China. In addition, the A allele is likely a protective gene for ischemic cerebrovascular disease.

The Mechanisms of SAA/TLR4 Inducing Angiogenesis in Rheumatoid Arthritis through NETs Formation

Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which angiogenesis represents a critical early event of synovial inflammation. The present study aimed to reveal the potential molecular mechanisms of SAA/TLR4 induction of angiogenesis through NETs in RA. Materials and methods: Firstly, immunohistochemistry and immunofluorescence were used to determinate TLR4 and NETs expression in synovial tissue, respectively. ELISA was used to detect the content of SAA, MPO and NE in serum and synovial fluid of patients. DNA quantification was done by fluorescence. DNA fluorescence staining was used to compare NETs formation in RA and HC sera, and to investigate the mechanism of NETs formation induced by SAA stimulation. PicoGreen DNA testing was used to characterize the DNA in the supernatants. Also, DNA fluorescence staining to explore whether NETs formation induced by SAA was dependent or independent on NADPH oxidase pathway. MTT assay, Wound healing assay, Tube formation assay were performed to analyze human veins umbilical cells (HUVECs) proliferation, migration, and tube vessels formation, respectively under NETs or NETs + DNase stimulants. Results: Firstly, we demonstrated that TLR4 was predominantly and widely expressed in synovial tissues with elevated serum levels of SAA, compared to osteoarthritis (OA) patients, and the similar results were observed for NETs formation. Afterwards, in a series of in vitro experiments, we reported an increased MPO and NE levels, and a relatively decreased DNA level in the sera of RA patients. Set apart, the levels of MPO and NE in RA were correlated to the disease activity. Moreover, an increased spontaneous NETs formation was observed in RA patients, enhanced under SAA stimulation and regulated by TLR4 activation. And the total DNA expressed in RA patients was partly composed of NET-DNA. Also, SAA induced NETs formation dependent on NADPH pathway. Finally, our results indicated that extracted SAA-induced NETs promoted endothelial cells (ECs) migration, proliferation, and vascular tube formation. Conclusion: Our current study highlighted the role of SAA/TLR4 interaction in the induction of angiogenesis through formed NETs. Therefore, this study offers new perspectives in the understanding of RA pathogenicity and its management.

Research Progress of Echocardiography Combined with Blood Related Detection Indexes in the Diagnosis and Treatment of Kawasaki Disease in Children

Aim: To explore the research progress of echocardiography combined with blood-related detection indicators in the diagnosis and treatment of Kawasaki disease in children. By collecting relevant literature reports, echocardiography and several blood-related detection indicators such as SAA, IL-6, PCT and CRP were screened out. It has good clinical application value in the clinical diagnosis and treatment of Kawasaki disease in children, but there is no report on the application of echocardiography combined with blood SAA, IL-6, PCT and CRP detection in the diagnosis and treatment of Kawasaki disease in children. The author intends to explore the role of echocardiography combined with blood SAA, IL-6, PCT and CRP detection in the diagnosis and treatment of Kawasaki disease in children, hoping to achieve better results.

Serum amyloid P component:a new biomarker for low sperm concentration?

Serum amyloid P component(SAP)is present in seminal plasma,on spermatozoa,and in different tissues of the male reproductive tract,but its function is not known.The aims of this study were to determine if the concentration of SAP in seminal plasma is associated with commonly assessed semen parameters and to investigate if SAP could be a new,indirect biomarker for these parameters.In a cross-sectional study of 203 young volunteers,the concentration of SAP in seminal plasma was measured with a in-house developed enzyme-linked immunosorbent assay.Scatter plots,Pearson’s correlation coefficients(r),and linear regression models were produced,and SAP showed a statistically significant correlation with sperm concentration(r=0.75),sperm number(r=0.68),semen volume(r=-0.19),progressive sperm motility(r=0.24),and sperm immotility(r=-0.20).When the study group was dichotomized,SAP could be used to discriminate samples with a sperm concentration<or≥5×10^(6)ml^(-1),15×10^(6)ml^(-1),or 40×10^(6)ml^(-1),and in receiver operating characteristic curves,the corresponding areas under the curves were 0.97,0.93,and 0.82,respectively,with P<0.001 for all three cutoff values studied.The concentration of SAP in seminal plasma showed a strong,positive correlation with the concentration of spermatozoa in semen.SAP may be used as a new indirect potential biomarker for sperm concentration in fresh and in frozen,stored samples.In addition,it is envisaged that the assay could be developed into a home fertility test to differentiate between a low and a normal sperm concentration.