Value of 18F-FDG PET/CT combined with tumor markers ProGRP and NSE in diagnosis and differential diagnosis of stageⅠA small cell lung cancer / 中华核医学与分子影像杂志

Objective:To explore the value of 18F-FDG PET/CT combined with pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) in diagnosis and differential diagnosis of stageⅠA small cell lung cancer (SCLC). Methods:From June 2017 to October 2021, 113 patients (75 males, 38 females; age 32-79 years) with stageⅠA lung cancer (70 with adenocarcinoma, 25 with squamous cell carcinoma, 18 with SCLC; patients with adenocarcinoma and squamous cell carcinoma were combined into non-SCLC (NSCLC) group) and 30 patients with benign pulmonary nodule (21 males, 9 females; age 37-77 years) from the Affiliated Qingdao Central Hospital of Qingdao University were retrospectively analyzed. All patients were examined by 18F-FDG PET/CT and serum tumor markers associated with lung cancer. Differences of the clinical, imaging and tumor markers data among different groups were analyzed by χ2 test, Fisher exact test and Kruskal-Wallis rank sum test. Independent risk factors were analyzed by logistic regression analysis and ROC curve analysis was used to analyze the value of different predictive factors in diagnosis and differential diagnosis of SCLC. Results:There were significant differences in SUV max, lobulation sign, spiculation sign, calcification, pleural traction sign, ProGRP, NSE and carcinoembryonic antigen (CEA) among SCLC, NSCLC and benign nodules groups ( H values: 14.06-20.54, χ2 values: 8.16-14.95, all P<0.05), in which lobulation sign of SCLC was more than that of benign nodules (12/18 vs 26.7%(8/30); χ2=7.41, P=0.007), spiculation sign (2/18 vs 51.6%(49/95); χ2=10.01, P=0.002) and pleural traction sign (1/18 vs 35.8%(34/95); χ2=6.47, P=0.011) were less than those of NSCLC, SUV max was higher than that of benign nodules (7.4(5.8, 9.0) vs 2.3(1.4, 5.1); H=51.82, P<0.001), ProGRP was higher than that of NSCLC and benign nodules (64.0(40.1, 84.8) vs 38.7(26.9, 47.6), 36.7(29.1, 40.5) ng/L; H values: 36.13, 43.96, P values: 0.002, 0.001) and NSE was higher than that of benign nodules (12.4(10.9, 14.5) vs 7.4(5.4, 11.8) μg/L; H=40.53, P=0.001). When differentiated SCLC from NSCLC, spiculation sign (odds ratio ( OR)=0.043, 95% CI: 0.004-0.450, P=0.009) and ProGRP ( OR=1.083, 95% CI: 1.035-1.133, P<0.001) were independent risk factors for SCLC, and the AUC of the two factors combination was 0.875, with the sensitivity and specificity of 14/18 and 84.2%(80/95). When differentiated SCLC from benign nodules, SUV max( OR=2.706, 95% CI: 1.099-6.662, P=0.030), ProGRP ( OR=1.165, 95% CI: 1.009-1.344, P=0.038) and NSE ( OR=1.639, 95% CI: 1.016-2.645, P=0.043) were independent risk factors for SCLC, and the AUC of the three factors combination was 0.985, with the sensitivity and specificity of 17/18 and 96.7%(29/30). Conclusion:18F-FDG PET/CT combined with tumor markers ProGRP and NSE is helpful to improve the diagnosis and differential diagnosis of stage ⅠA SCLC.

The clinical research progress in serum Presepsin / 中华检验医学杂志

Presepsin(sCD14-ST), is an soluble leukocyte differentiation antigen 14 subtype. It is a glycoprotein fragment and a marker of acute phase reaction. For diagnosis of adult sepsis, bacteremia and bacterial DNAaemia, the area under of ROC is 0.88,0.78 and 0.79, respectively. The levels of Presepsin increase earlier than procalcitonin, and have better clinical value for early diagnosis of sepsis. It is significantly correlated with disease severity and can be used to predict prognosis. One study mentioned that in the absence of organ dysfunction, the value was 235.0 (172.0-340.3) pg/ml, and for one, two, three or more organ dysfunction, were 403.5 (275.8-587.3) pg / ml, 844.5 (559.8-1259.5) pg / ml, 1412.5 (893.0-2675.8) pg/ml (P<0.01), respectively. Another study mentioned that Presepsin is an independent risk factor for 30-day death of sepsis, and it is effective to evaluate poor prognosis with a threshold of >927.5 pg/ml. Presepsin also has clinical value for neonatal and child sepsis. The Greece meta-analysis showed that the AUC for neonatal sepsis diagnosis was 0.9751, which was higher and more sensitive than that of CRP and procalcitonin. Turkish study on children showed a significant increase in sCD14-ST in sepsis patients compared with healthy controls. Its AUC was 0.98, the best threshold was 990 pg/ml. The reference range of this value was been studied, showing that 75％ and 95％ percentiles of full-term infants are 791 and 1178 pg/ml. Adults do not exceed 200 pg/ml of all age groups. It is affected by renal function. Prospective trials are expected to further clarify its diagnostic value, more therapeutic research to elaborate its therapeutic value, and corresponding clinical practice guideline.

Age-related Reference Intervals for Total Collagen-I-N-terminal Propeptide in Healthy Korean Population

BACKGROUND: Procollagen type I N-terminal propeptide (PINP) is one of the most clinically useful bone formation biomarkers. Therefore, the purpose of this study was to independently evaluate the performance of automated total PINP assay and established age- and gender-specific reference intervals for PINP in healthy Korean population. METHODS: The imprecision, linearity, and detection capability of Elecsys total PINP assay was determined and reference interval was established using 599 serums from Korean population with normal bone mineral densities based on bone densitometry. Age groups were divided into 20s, 30s, 40s, 50s, 60s and over. RESULTS: Elecsys total PINP had excellent performance in imprecision, linearity, and detection capability. When partitioning age groups in Korean male and female populations, there was significant difference in total PINP between different age groups. In male populations, PINP level was decreased with increasing age, then it remained steady after middle-age. In female populations, there was a decreasing tendency similar to that in the male population with a sharp increase in the 50 to 59 age group. CONCLUSIONS: Elecsys total PINP assay showed precise and reliable performance in our study. We established age-related PINP reference intervals for Korean male and female population with normal bone mineral densities.

Application of bone metabolism markers tP1NP,beta-CTx and BAP in bone metastasis of lung cancer / 中华检验医学杂志

Objective To investigate the diagnosis, therapeutic monitoring and prognosis value of the total procollagen type 1 amino-terminal propeptide(tP1NP), beta-C-terminal telopeptide(β-CTx)and bone alkaline phosphatase(BAP)in the bone metastasis of lung cancer.Methods With the case-control study method, the serum levels of tP1NP, β-CTx and BAP in 196 lung cancer patients, including 109 patients with bone metastases,87 patients without bone metastases,and 106 healthy controls at the Shanghai Sixth People′s East Hospital affiliated to Shanghai Jiao Tong University between 2014 and 2015 were quantitatively detected by chemiluminescent immunoassay.Receiver operating characteristic(ROC)curve was calculated to assess the diagnostic value.Survival curve was performed by Kaplan-Meier method. Results The concentration of tP1NP,β-CTx and BAP in the lung cancer patients with bone metastasis were significantly higher than that in the lung cancer patients without bone metastasis(Z=-5.642,P<0.001;Z=-3.783,P<0.01;Z=-8.923,P<0.01).ROC curve analysis showed that the AUC of tP1NP, β-CTx and BAP were 0.874,0.776 and 0.678 respectively(P<0.05).The AUC of the combined three markers was 0.925(95%CI 0.867-0.963),with sensitivity of 77.11% and specificity of 98.11%.The levels of tP1NP and β-CTx were associated with the clinical response.The concentration of tP1NP,β-CTx were significantly decreased in patients achieved remission(t=4.607,P<0.05;t=5.355,P<0.05). Survival analysis showed that higher concentration of tP 1NP was correlated with poor prognosis[OR=3.287, 95%CI(1.118-9.661),P<0.05].Conclusions The levels of tP1NP,β-CTx and BAP cloud be used for the differential diagnosis of bone metastasis of lung cancer,and the combined usage was more effective. tP1NP and β-CTx cloud be used in therapeutic monitoring of lung cancer patients with bone metastasis. Moreover,tP1NP could be used as prognostic biomarker in lung cancer patients.

Brain renin-angiotensin system: a potential therapeutic target for ischemic stroke / 国际脑血管病杂志

Brain renin-angiotensin system (RAS) is closely associated with many pathophysiological processes of cardiocerebrovascular diseases,including stroke.The activation of the different components in RAS will produce specific biological effects.This article reviews the roles of brain RAS in the pathophysiological processes of ischemic stroke,especially the neuroprotective effect of ACE2/Ang-(1-7)/Mas axis.

Re-understand the clinical significance of natriuretic peptide family / 中华检验医学杂志

Although BNP/NT-proBNP has been widely accepted as the gold standard biomarker for the diagnosis and prognosis of heart failure, and current guidelines on heart failure list the application of natriuretic peptide in the diagnosis and prognosis of heart failure as ⅠA recommendations, the latest studies discovered a lot of new finding, which show that some of our thoughts on the test result of BNP/NT-proBNP is wrong. It is important for clinical and laboratory physicians to understand the latest progress on natriuretic peptide family. It will help them use BNP/NT-proBNP more properly. In the future, as the new drugs, which work via natriuretic peptide family, will be used widely in patients, the test of natriuretic peptide family will become more important.

Effects of glycomacropeptide in human milk and formula milk on proliferation ofbiifdobacterium infantis in vitro / 中华围产医学杂志

ObjectiveTo explore the effects of glycomacropeptide (GMP) in human milk and formula milk on proliferation ofbifidobacterium infantis and their dose-response relationship.Methods Casein was isolated from the milk of 30 healthy postpartum women from Guangzhou Women and Children's Medical Center in September 2014, and hydrolyzed by rennet to obtain GMP, which was then purified by ultrafiltration and ion exchange chromatography. Human milk GMP and cow milk GMP (0, 250, 500, 1 000, 1 500, 2 000 and 3 000 mg/L) were added tobifidobacterium infantis liquid medium, and cultured under anaerobic conditions. Concentration of bacteria was measured by turbidimetric microplate assay (detection of OD600 nmvalue of medium). Difference of proliferative activities ofbiifdobacterium infantis in human milk GMP and cow milk GMP was compared with independent samplest-test.ResultsPurified human milk GMP concentration was 1 712.20 mg/L, with a purity of 80.3%. Increasing the cow milk GMP initial concentration in the culture medium at 250-2 000 mg/L could increase the concentration and proliferation rate ofbiifdobacteria infantis. When cultured at 36 h with GMP of various concentrations, the proliferation ofbiifdobacteria infantis maintained at a logarithmic phase. Therefore, 36 h was chosen as the test time point to compare the proliferation ofbifidobacterium infantis. At 36 h, when GMP in the medium was 1 000, 1 500, 2 000 and 3 000 mg/L, concentrations ofbiifdobacteria infantis in human milk GMP were 2.255±0.036, 2.583±0.088, 2.877±0.080 and 3.219±0.081, respectively, which were significantly higher than those in cow milk GMP (2.115±0.053, 2.312±0.064, 2.542±0.090 and 2.894±0.076;t=4.867, 5.569, 6.192 and 6.516; allP<0.01).Conclusions Both human milk GMP and cow milk GMP can promote the proliferation ofbiifdobacterium infantisin vitro, and the proliferative activity in human milk is greater than in cow milk at the same concentration of GMP.

Pathologic features of fallopian tubal fimbriae in patients with endometrial serous carcinoma / 中华妇产科杂志

Objective To discuss the potential relationship between endometrial serous carcinoma (ESC) and tubal epithelial lesions by pathologic examination of fallopian tubes with ESC. Methods A total of 30 cases of typical ESC were reexamined and chosen by the pathologist. In each case, bilateral fallopian tubes were submitted to examination of pathologic morphology and immunostaining for p53, annexin Ⅳ(ANX-Ⅳ), human epidermal growth factor receptor 2(HER2)/neu, and high-mobility group protein A2 (HMGA2). Results Fallopian tubal epithelial lesions were found in 15 cases, including 9 cases tubal serous carcinoma, 2 cases serous tubal intraepithelial carcinoma (STIC) and 2 cases epithelial hyperplasia. Both sides of tubal serous carcinoma and STIC were found in 1 case. The results showed the positive expression for p53 in 26(87%)out of 30 endometrial malignant specimens tissues and 9(30%)tubal tissues samples (P>0.05). Twenty-five(83%)endometrial malignant specimens tissues and 6(20%)tubal tissues samples showed the positive expression of ANX-Ⅳ. Twenty-one(70%)endometrial malignant tissues and 7(23%) tubal tissues showed the positive expression of HER2/neu. Twenty-five(83%) endometrial malignant tissues and 6(20%)tubal tissues showed the positive expression of HMGA2. While, there were significant differences among the expression of three proteins between endometrium and the fallopian tube site (all P<0.05). Conclusions STIC may be associated with the occurrence of ESC. The expression of p53 was positively correlated between the fallopian tube and the endometrium. ANX-Ⅳ,HER2/neu and HMGA2 were extensively expressed in ESC.

The performance evaluation of soluble ST2 detection kit and the clinical application of sST2 in diagnosing heart failure / 中华检验医学杂志

Objective To evaluate the performance of sST 2 ELISA kit and investigate the clinical application of sST2.Methods This verification study validated the precision , linearity of sST2 ELISA kit according to the CLSI EP-15A, EP-6A protocols.300 healthy adults(aged from 20 to 85, 124 male and 176 female) from 5 different districts of Shanghai were used to establish serum sST 2 reference interval .The correlations between sST2, NT-ProBNP, LVEF and NYHA class were analyzed in 117 patients diagnosed with heart failure who were grouped according to the New York heart association ( NYHA).Receiver operating characteristic (ROC) curve was used to compare the ablity of sST2, NT-ProBNP, LVEF in distinguishing heart failure patients .Results The within-lot and between-lot variation of three level samples were below 4% and 10% respectively.There was a good linear correlation ( Y=0.995X+0.005, R2 =0.999) between theoretical value and actual detection result in the range of 0 to 200 μg/ml.The reference interval of sST2 was 10.2 to 41.0μg/ml for males and 8.9 to 28.1μg/ml for females.sST2 was positively correlated with NT-ProBNP and NYHA class but did not correlate with LVEF in heart failure patients . Patients with NYHA class>II (Median:28.3,IQR:19.5-39.2)had higher serum sST2 level than patients with NYHA class≤II (Median:45.1,IQR:34.1 -85.6), PII were 0.743, 0.810, 0.831 respectively and the sensitivity of sST 2 +NT-ProBNP+LVEF was 94.7%.Conclusions Experimental results show that this sST 2 ELISA kit has a good performance in the precision, linearity.sST2 correlates with NT-ProBNP and NYHA class but do not correlates with LVEF . Serum sST2 level is not influenced by age , BMI, renal function.sST2 could be a good supplement of NT-ProBNP and LVEF in distinguishing patients between NYHA class≤II and>II.

Development and performance evaluation of a novel quantitative fluorescence immunochromatography for NT-proBNP / 中华检验医学杂志

Objective To develop a rapid quantitative detecting assay for point-of-care testing ( POCT ) of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) in serum by the fluorescence immunochromatographic technology.Methods Applying double-antibody sandwich assay to establish the quantitative NT-proBNP kit.The performance of quantitative NT-proBNP kit was evaluated by the sensitivity , specificity, accuracy, precision, stability and clinical effectiveness.It compared the research kit and conference kit by the parallel experience in the 1 056(605 males, 451 females)serum specimen collected from Guangdong Provincial People′s Hospital, Sun Yat-sen Memorial Hospital and Children′s Hospital of Zhengzhou between February 2013 to April 2014.Statistical significance of the results was assessed by correlation analysis , linear regression , receive operating characteristic ( ROC) curve analysis , negative and positive consistent.Results The report range of the NT-proBNP kit was 18-35 000 ng/L.The coefficient of variation ( CV) values for low , median and high concentration calibrators respectively were all less than 15%.Common interfering substances in human serum specimens such as bilirubin , triglyceride and cholesterol were found no significant affect on NT-proBNP antigen detection and the CV were no more than 15%.According to the results of detection for calibrators , the shelf time of the NT-proBNP diagnostic kit should be longer than 12 months.The NT-proBNP kit and reference kit had good correlation ( Y=1.048 9X developed reference +121.54, R2 =0.956 6, n=1 056) to detect the target protein through the parallel experiments and the deviation of the quantitative results of clinical serum samples showed no statistical significance (Z=0.88, P=0.379>0.05).The clinical assays of two different diagnostic kits showed good consistency based on the ROC curve evaluation which is compared by two cut-off values (300 and 450 ng/L).The areas under ROC curve were 0.981 and 0.978 respectively.Conclusions A novel NT-proBNP chromatographic quantitative immunofluorescence detection method was developed in this study .The performance evaluation data indicated that the kit is suitable for rapid detection of serum NT -proBNP.

How can we know if treatment for heart failure is effective? / Como saber se o tratamento da insuficiência cardíaca é eficaz?

Heart failure is a disease that progresses with high morbidityand mortality, but the correct treatment using neurohormonal inhibitors could alter its natural history. Although more and more patients have been treated, drugs are sometimes prescribed at doses lower than those known to be effective. In heart failure, a marker of treatment efficacy is lacking, since symptomatic improvement does not indicate that the patient will remainstable in the long term. The aim of this study was to evaluate the need for a marker of improvement during treatment. Reverse remodeling, present in clinical trials of drugs that reduced the mortality of patients with heart failure, is a marker of good response to treatment and can be used as a marker of treatment efficacy. Lack of reverse remodeling is indicative of greater severity of the case or of insufficient treatment. The same is true of the analysis of hemodynamic response when there is a reduction in intracardiac pressures, documenting that the treatment is effective. The persistence of heart rate above 70 bpm is another important marker of poor prognosis, and indicative of the need for treatment optimization. Reverse remodeling,improved ejection fraction, hemodynamic improvement, andreduction in heart rate are markers of treatment efficacy and are followed by significant reduction in mortality, and may be used to guide treatment...

A insuficiência cardíaca é uma doença que evolui com alta morbimortalidade, mas o tratamento correto, que emprega bloqueadores neurohormonais, pode modificar sua história natural. Embora cada vez mais os pacientes recebam tratamento, muitas vezes os fármacos são prescritos em doses menores do que as reconhecidas como eficazes. Na insuficiência cardíaca, falta um marcador de eficácia do tratamento, pois a melhora sintomática não indica que o paciente permanecerá estável em longo prazo. O objetivo deste estudo foi avaliar a necessidade de emprego marcador de melhora durante o tratamento. A reversão da dilatação cardíaca, presente nos ensaios clínicos dos fármacos que reduziram a mortalidade dos portadores de insuficiência cardíaca, é um marcador de boa resposta ao tratamento e pode ser empregada como marcador de eficácia do tratamento. A ausência de reversão é indicativa de maior gravidade do casoou de tratamento insuficiente. O mesmo é verdadeiro em relação à análise da resposta hemodinâmica, quando ocorre redução das pressões intracardíacas, documentando que o tratamento está sendo eficaz. A persistência de frequência cardíaca acima de 70 bpmé outro marcador importante de pior prognóstico e indicativo de necessidade de melhora no tratamento. A reversão da dilatação cardíaca, a melhora da fração de ejeção, a melhora hemodinâmica e a redução da frequência cardíaca são marcadores de eficácia do tratamento e são acompanhadas de redução significativa da mortalidade, podendo ser empregadas para orientar o tratamento...

Valor prognóstico do fragmento N-terminal do peptídeo natriurético tipo B em cirurgia não-cardíaca / Prognostic value of perioperative N-terminal pro-B-type natriuretic peptide in noncardiac surgery

FUNDAMENTO: Já foi demonstrado o uso do NT-proBNP pré-operatório para prever resultado cardíaco adverso, embora estudos recentes tenham sugerido que a determinação do NT-proBNP pós-operatório possa fornecer um valor adicional em pacientes submetidos à cirurgia não cardíaca. OBJETIVO: Avaliar o valor prognóstico perioperatório do NT-proBNP em pacientes de intermediário e alto risco cardiovascular submetidos à cirurgia não cardíaca. MÉTODOS: Este estudo incluiu prospectivamente 145 pacientes com idade > 45 anos, com pelo menos um fator de risco do Índice de Risco Cardíaco Revisado e submetidos à cirurgia de médio ou alto risco não-cardíaca. Os níveis de NTproBNP foram medidos no pré e pós-operatório. Preditores cardíacos de curto prazo foram avaliados por modelos de regressão logística. RESULTADOS: Durante uma mediana de acompanhamento de 29 dias, 17 pacientes (11,7%) apresentaram eventos cardíacos adversos importantes (MACE - 14 infartos do miocárdio não fatais, 2 paradas cardíacas não-fatais e 3 mortes cardíacas). Os níveis ótimos de limiar discriminatório para o NT-proBNP pré e pós-operatório foram 917 e 2962 pg/ mL, respectivamente. O NT-proBNP pré e pós-operatório (OR = 4,7, IC 95%: 1,62-13,73, p = 0,005 e OR 4,5, IC 95%: 1,53-13,16, p = 0,006) foram associados de forma significativa com MACE (eventos cardíacos adversos maiores). O NTproBNP pré-operatório foi significativa e independentemente associado com eventos cardíacos adversos em análise de regressão multivariada (OR ajustado 4,2, IC 95%: 1,38-12,62, p = 0,011). CONCLUSÃO: O NT-proBNP é um importante marcador de curto prazo de eventos cardiovasculares perioperatórios em pacientes de alto risco. Os níveis pós-operatórios foram menos informativos do que os níveis pré-operatórios. Uma única medição de NT-proBNP pré-operatório deve ser considerada na avaliação de risco pré-operatório.

BACKGROUND: Preoperative NT-proBNP has been shown to predict adverse cardiac outcomes, although recent studies suggested that postoperative NT-proBNP determination could provide additional information in patients submitted to noncardiac surgery. OBJECTIVE: To evaluate the prognostic value of perioperative NT-proBNP in intermediate and high risk cardiovascular patients undergoing noncardiac surgery. METHODS: This study prospectively enrolled 145 patients aged >45 years, with at least one Revised Cardiac Risk Index risk factor and submitted to intermediate or high risk noncardiac surgery. NT-proBNP levels were measured pre- and postoperatively. Short-term cardiac outcome predictors were evaluated by logistic regression models. RESULTS: During a median follow-up of 29 days, 17 patients (11.7%) experienced major adverse cardiac events (MACE- 14 nonfatal myocardial infarctions, 2 nonfatal cardiac arrests and 3 cardiac deaths). The optimum discriminatory threshold levels for pre- and postoperative NT-proBNP were 917 and 2962 pg/mL, respectively. Pre- and postoperative NT-proBNP (OR 4.7; 95% CI 1.62-13.73; p=0.005 and OR 4.5; 95% CI 1.53-13.16; p=0.006) were significantly associated with MACE. Preoperative NT-proBNP was significantly and independently associated with adverse cardiac events in multivariate regression analysis (adjusted OR 4.2; 95% CI 1.38-12.62; p=0.011). CONCLUSION: NT-proBNP is a powerful short-term marker of perioperative cardiovascular events in high risk patients. Postoperative levels were less informative than preoperative levels. A single preoperative NT-proBNP measurement should be considered in the preoperative risk assessment.

Value of pro-GRP and NSE in the diagnosis of small-cell lung cancer difference and combination detection / 中华检验医学杂志

Objective To study the serum levels of progastrin-releasing peptide (pro-GRP) and neuron-specific enolase (NSE) for the clinical diagnosis,therapy monitoring and survival time analysis of small cell lung cancer (SCLC).Methods All 41 SCLC samples (30 males,11 females,age range from 46 to 78 years),95 NSCLC samples (55 males,40 females,age range from 42 to 88 years),and 127 normal individuals samples (80 males,47 females,age range from 35 to 78 years) which were diagnosed by People's Hospital of Zhengzhou from May 1,2008 to April 30,2011 were collected.Serum levels of pro-GRP,NSE and their changes in SCLC patients before and after therapy were evaluated.ANOVA analysis,randomized block design analysis of variance and the log-rank test were collected SPSS 16.0 to evaluate the survival time.Results The serum levels of pro-GRP (median 357.8 ng/L) and NSE (median 89.5 μg/L) in SCLC group were significantly higher than those in the NSCLC group (pro-GRP:39.9 ng/L;NSE:11.43 μg/L) and normal individuals group (pro-GRP:12.7 ng/L;NSE:10.03 μg/L) (P=0.000).The sensitivity of pro-GRP and NSE for the diagnosis of SCLC were 80.4％ and 78.0％,while the specificity were 92％ and 87％,respectively.There is a poor correlation between pro-GRP and NSE serum levels,but when combined the sensitivity can be 95％ and specificity can be 85％.Significantly statistical difference of pro-GRP levels was observed in the different stages of treatment (before and after therapy) in SCLC-LD patients (F =3.53,P =0.038),and significant statistical difference of NSE levels was also observed in SCLC-ED patients in different stages (F =16.049,P =0.000).In partied response SCLC patients,the group with NSE level lower than cut-off value had longer survival time than the other group with NSE level higher than cut-off value (P =0.001).Conclusions The sensitivity of the combined analysis of pro-GRP and NSE is better than single marker for the diagnosis of SCLC.The serum level of pro-GRP has better correlation with therapeutic effect of SCLC-LD patient than NSE.The serum level of NSE are well correlated with therapeutic effect in SCLC-ED patients.There are some certain value of NSE level for evaluation the survival time of SCLC patients who were in partial response.

Diagnostic value and prognosis assessment of ProGRP for small cell lung cancer / 中华检验医学杂志

Objective The purpose of this study was to discuss the clinical significance of serum levels of Pro-gastrin-releasing peptide (ProGRP) in diagnosis,therapy monitoring and prognosis in patients with small cell lung cancer (SCLC).Methods Clinical diagnostic trial.Serum levels of ProGRP were measured by ELISA assays in 413 SCLC patients,418 NSCLC,120 with benign pulmonary diseases patients and 200 healthy subjects.Patients were recuited by the Shanxi Cancer Hospital from Dec.2005 to Oct.2008.Three hundreds and sixty-eight patients with SCLC were followed up from Dec.2005 to Oct.2011.The receiver operating characteristic curves (ROC) was used to set the cut-off value of ProGRP and the area under ROC (ROC-AUC).The sensitivity and specificity of ProGRP were analyzed for diagnosing SCLC.The survival analysis was performed by the Kaplan-Meier method and Cox's proportional hazards model for multivariate analysis of prognosis.Results Using healthy subjects group as control,the largest Youden index point of ROC was used to set the cut-off values of ProGRP and NSE (45.3 ng/L and 12.4 ng/L).The ROC-AUC of ProGRP was 0.798 (95％ CI:0.746-0.850)the sensitivity and specificity were 79.2％,98.1％ respectively.The AUC of NSE was 0.786(95％ CI:0.726-0.746),the sensitivity and specificity were 71.9％,96.7％ respectively; Combing detection of ProGRP and NSE,the sensitivity and specificity were 88.1％,95.8％ respectively.Serum levels of ProGRP in healthy subjects,benign pulmonary diseases,NSCLC and SCLC groups were 6.9 (5.3-8.6),36.8 (26.3-43.4),21.3 (18.6-35.2) and 1758.7 (368.4-2967.3) μg/L respectively.The serum levels of ProGRP in SCLC groups were significantly higher than those in the healthy group,benign pulmonary diseases group and NSCLC group (H =103.66,P =0.000).Serum levels of ProGRP in SCLC at stage Ⅰ-],stage m,stage Ⅳ were 543.3 (256.8-843.2),1440.6 (1042.4-2543.3) and 1897.6 (1586.5-3958.7) μg/L,respectively (H =25.974,P =0.000).Serum levels of ProGRP in 165 SCLC patients with complete remission(CR) were significantly declined after treatment (U =11.65,P ＜ 0.01).The levels of ProGRP in 146 SCLC patients with partial remission(PR) slowly decreased (U =9.17,P ＜ 0.01).Thirty-nine cases with progressive disease (PD)and 63 cases with stable disease(SD) presented elevated ProGRP levels (U =3.314,P ＜ 0.001 ; U =2.54,P ＜ 0.01,respectively).By the end of October 31st 2011,a total of 368 cases with SCLC were followedup.Ratio of follow-up was 89.1％.There were 56 deaths in 119 SCLC patients with ProGRP ＜ 1000 μg/L (median time =16.0 months,4-23 months) ; 159 deaths in 249 with ProGRP ＞ 1000 μg/L (median survival time =12.0 months,2-18 months).Median survival time of the two groups showed significant differences(x2 =11.04,P =0.001).Multivariate analysis by Cox's proportional hazards model revealed that ProGRP was independent prognostic factor related to the overall survival (OS) of SCLC patients.Conclusions The serum ProGRP is valuable tumor marker for diagnosis,treat monitoring and prognosis of SCLC.It's important to predict relapses and recurrence of diseases earlier,instruct therapy and prognosis assessment.

N-Terminal pro-brain natriuretic peptide and ischemic stroke / 国际脑血管病杂志

Brain natriuretic peptide (BNP) is one of the most sensitive and specific laboratory indicators during cardiac dysfunction.N-Terminal pro-brain natriuretic peptide (NT-proBNP) is the N-terminal precursor of BNP.The functions of both are not consistent,but its physicochemical properties are superior to BNP.Now it has been widely used in the diagnosis and treatment monitoring of cardiovascular diseases.In the field of stroke,the testing and application of BNP,especially NT-proBNP is less.This article reviews the roles of NT-proBNP in cardio-cerebrovascular diseases,especially in ischemic cerebrovascular disease.

Establishment of the test method of the Aβ42 in the serum of the alzheimer disease patient and its clinical significance / 中华检验医学杂志

ObjectiveTo establish a enzyme-linked immunosorbent assay (ELISA) method for detecting the β-amyloid peptide 42 ( Aβ42 ) and explore its clinical meaning for diagnosis and treatment in the early stages of the alzheimer disease ( AD).Methods Using the Aβ42 single chain variable fragment constructed by phage antibody library display system as coat antibody,associated with the Aβ42 polyclonal antibody acquired by Aβ42 immunized rabbit and HRP labeled goat anti rabbit IgG to establish ELISA method for detecting the Aβ42 in peripheral blood.The method was used it to test the Aβ42 in 120 vascular dementia VD) or cerebral vessel infarction patients and 120 AD patients and 120 controls.The methodology performance were evaluated.ResultsThe inter and intra coefficient of variable (CV) of this self-established ELISA method was 3.6％ and 3.5％,6.8％ and 7.1％ respectively.The recovery rate was 97.2％ -103.1％.The linear range was 0.050 - 2 μg,/L.Its reactivity decreased ＜ 12％ when it was put in both 37 ℃ for 6 days and 4 ℃ for 6 months.Compared with the Belgium INNOTEST reagent by testing 90 samples simultaneously,the results of self-established method was (0.207 ± 0.039 ) μg/L,the results of INNOTEST was (0.206± 0.038 ) μg/L; the regression equation was Y =1.011X - 0.003,R2 =0.979,P ＜0.01.The Aβ42 in blood of AD group was (0.247 ± 0.032 ) μg/L,VD or cerebral vessel infarction group was (0.173 ±0.028) μg/L,control group was (0.172 ±0.032) μg/L.The Aβ42 in AD group was higher than that in the VD or cerebral vessel infarction group and control group (q =18.867,18.907respectively,P ＜ 0.01 ).The cut off value was 0.212 μg/L decided by the receiver operating characteristic (ROC) curve.The reference interval was 0 -0.212 μg/L.The sensitivity of this ELISA method was 86.7％(104/120) and specificity was 90.8％ (218/240).ConclusionsThe ELISA method for detecting Aβ42 in peripheral blood established by the study is sensitive and specific and has good precision and stability.It could provide a new effective criterion and support for the early diagnosis and treatment of the AD patients.

Role of BNP and NT-proBNP in clinical application / 中华检验医学杂志

The precursor of B-type natriuretic peptide (proBNP) is cleaved by a specific enzyme into the biologically active BNP and biologically inactive N-terminal fragment (NT-proBNP).Plasma BNP and NT-proBNP concentrations are affected by gender,age,obesity (higher BMI) and renal function.BNP is primary metabolized by clearance receptors,NT-proBNP is suggested by renal excretion,so plasma concentrations of NT-proBNP are more affected by renal function than that of BNP.The differential diagnosis of acute dyspnea and acute heart failure (AHF) is one of the most important clinical applications of BNP and NT-proBNP.Two cut-off points were used:a lower one with a high negative predictive value to reliably exclude acute heart failure (AHF) as the cause of acute dyspnoea (rule-out cutoff value),and a second higher one with a high positive predictive value to rule in AHF as the cause of dyspnoea (rule-in cutoff value).The rule-in cutoff values of NT-proBNP divided into three levels according to the age,these cutoff values apply irrespective of gender,obesity and renal function,but the rule-in cutoff point of BNP need to be corrected by obesity and renal function.In addition,BNP/NT-proBNP has been shown to provide diagnosis,prognosis and therapy-guiding information in chronic heart failure and coronary heart disease.

Progress in the mechanism of plasma N-terminal pro-brain natriuretic peptide in children with Kawasaki disease / 国际儿科学杂志

Kawasaki disease ( KD) is an acute febrile systemic vasculitic syndrome. Since there is no specific diagnostic test for KD, the diagnosis is mainly based on the clinical menifetations according to the criterias and excluding of other diseases. Recently the value of plasma brain natriuretic peptide ( BNP) in the diagnosis of KD has been paid more attention gradually. The plasma NT-proBNP level is significantly elevated in KD patients in the acute phase. It is of some specificity and sensitivity, and it may due to the local myocardial inflammation, cytokines and diastolic function of left ventricular. This review summarizes the mechanisms by which the elevated levels of plasma NT-proBNP occur in the acute phase of KD.

Application of serum levels of pro-gastrin releasing peptide, tissue polypeptide specific antigen and neuron specific enolase in therapy monitoring in small cell lung cancer patients / 中华检验医学杂志

Objective To evaluate the clinical significance of serum levels of ProGRP, TPS and NSE in diagnosis and therapy monitoring in small cell lung cancer patients. Methods The levels of serum ProGRP, TPS and NSE in 51 SCLC patients (SCLC group), 60 benign pulmonary disease patients (benign disease group ) and 60 healthy people (healthy group ) were determined using chemiluminescent immunoassay, ELISA and electrochemiluminescent immunoassay respectively. Blood samples were collected and detected prior to therapy, before the second course of chemotherapy and the third course of chemotherapy consecutively in all the 51 SCLC patients. Results The serum ProGRP, TPS and NSE concentrations prior to chemotherapy in limited stage SCLC (LSCLC) were 136. 9(22.8-631.7)ng/L, 78. 2(56.4-114.6) U/L and 28.1(20.9-46.1)μg/L, respectively; And in extensive stage SCLC patients (ESCLC) were 1 106.6(41.2-2161.1) ng/L, 230. 9( 143.5-259.0) U/L and 81.1 (34.3-140.0)μg/L, respectively. The serum concentrations of the 3 markers in benign disease group were 19. 7 ( 9. 5-29. 1 )ng/L, 48. 7 ( 17.9-95.4) U/L and 12. 1(1.2-13.9) μg/L; and in healthy group were 20.3(10.7-30.6) ng/L, 50.3(19.5-70.7) U/L and 11.7 (1.1-13.4)μg/L, respectively. The Kruskal-Wallis test showed significantly statistical difference in different groups of the 3 tumor markers, Chi-Square were 51. 368,36. 532 and 81. 645( P ＜0. 01 ). Significant statistically differences showed when the concentrations of the 3 marks of the 2 control group were compared with that of the LSCLC group ( U =491, 827, 609 and 476, 831, 585,respectively, P ＜ 0. 05 ). Differences were also statistically significant when the 2 control group compared with that of the ESCLC group ( U = 314,532,456 and 302,553,430, respectively, P ＜ 0. 01 ). The AUC of ProGRP was 0.832 +0.029(95% CI:0.774-0.890). When cutoff value of ProGRP set as 37.7 ng/L, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and Youden's index were 71% (36/51), 97% (116/120), 90% (36/40), 89% ( 116/131 ) and 67%, respectively; show good detection performance. The sensitivity increased to 92%, 86%, 92% and 88%, when combination detection of ProGRP + TPS + NSE, ProGRP + TPS, ProGRP + NSE and TPS + NSE were used, and the specificities were 77%, 77% , 92% and 77% accordingly. The Fridman test showed significantly statistical difference in the 3 tumor markers at different stages of treatment, x2 were 49. 120, 10. 614 and 44. 392, P ＜0. 01. After the first chemotherapy course, all the tumor marker levels except TPS decreased significantly in comparison with the pretreatment concentrations. However, only ProGRP levels showed a progressive drop during the two consecutive courses of therapy, and the median concentrations were 68.0 ( 18. 6-158.4 ) and 21.0( 14. 9-63.5) ng/L (compared to the level before therapy,Z=-4. 889 and -5. 594, P ＜0. 01 ). The median of serum TPS increased slightly to 105.2 (54. 1-181.2 ) U/L after the first chemotherapy course (Z=-1.248, P＞0.05), and decreased significantly to 79.0(48.7-155.3) U/L after the second chemotherapy course (Z=-2.484, P＜0. 05 ). As to the NSE, the median concentration decreased to 11.8(8.0-16.0)μg/L after the first chemotherapy course ( Z= - 5. 568, P ＜ 0. 01 ). However, the median was 10. 6(9.0-12.7)μg/L, which showed no significant decrease after the second chemotherapy course (Z=-1.851, P＞0.05).Forty-six SCLC patients evaluated as clinical remission ( 3 CR and 43 PR) after the second chemotherapy course, among them there were 38 patients (83%) with normal serum ProGRP, TPS and NSE level ( 19 patients) or with only 1 abnormal tumor level ( 19 patients). There were only 2 patients with all abnormal serum ProGRP, TPS and NSE level, and both patients were evaluated as clinical PD. Two patients with 2 abnormal tumors results were classified as SD, the only 1 patient without therapy evaluation also had 2 abnormal tumor marker results. Conclusions The serum ProGRP, TPS and NSE are valuable tumor markers for diagnosis and treat monitoring of SCLC, particularly the ProGRP + NSE shows the highest clinical value. Combing detection of the 3 tumor markers are valuable for therapy monitoring and prognosis in SCLC patients.

Evaluation of performance of a rapid immunofluorescence method for assaying plasma NT-proBNP / 中华检验医学杂志

Objective To analyze the performance of a rapid immunofluorescence assay for plasma NT-proBNP. Methods Human plasma NT-proBNP was measured by RAMP in 264 healthy cases and 78 patients with heart failure. The precision, stability, linearity and interference factors of RAMP were evaluated according to the protocold from America CLSI. Meanwhile, the results were compared with those obtained by Elecsys. Results Functional sensitivity of RAMP in 20% CV and 10% CV were 48 ng/L and 57 ng/L respectively. The linear range was 18-8 000 ng/L. NT-proBNP in plasma samples detected by RAMP were stable at room temperature for 24 hours, 4 ℃ for 3 days and - 20 ℃ for 20 days. No influences on results were observed throughout three freeze-thaw cycles. The results measured by RAMP were compared between EDTA-K2 anticoagulant plasma and heparin anticoagulant plasma, which showed that YEDTA-K2 =0. 953 9 Xheparin + 0. 365 2 ( R2 = 0. 982, P < 0. 01, n = 40 ). The results of EDTA-K2 and heparin anticoagulant plasma using RAMP and Elecsys showed no significant difference( P ＞0. 05). Slight hemolysis( Hb 2 g/L)had small effect on the results of PAMP and Elecsys assays and deviations of them were below 5%. However median and heavy hemolysis( Hb 3-4 g/L )obviously influenced the results with deviation were more than 15%. The values measured by RMAP fell from 390 ng/L to 82 ng/L, and those measured by Elecsys method fell from 390 ng/L to 178 ng/L when 3 different concentrations of triacylglycerol were added, the values measured by two methods fell from 7 777 ng/L to 7 741 ng/L when bilirubin ( 16-330 μmol/L) was added. The anti-interference ability of RAMP method was similar to Elecsys. Results detected with two methods in 45 EDTA-K2 anticoagulant plasma samples were analyzed with Passing and Bablok regression.The regression equation was YRAMP = 0. 972 8XElecsys - 0. 035 2 (R2 = 0. 994, P ＞ 0. 05, n = 45 ). When heparin anticoagulant plasma samples increased to 78 samples, Passing and Bablok regression equation showed:YRAMP= 0. 983 2XElecsys - 0. 037 6 ( R2 = 0. 991, P ＞ 0. 05, n = 78 ). NT-proBNP levels in healthy adults were elevated along with age and related to the gender. The median value of female[105(60-120) ng/L] was higher than that of male [59 ( 44-91 ) ng/L, Z = 3. 264, P < 0. 01] significantly. Conclusions RAMP method has good repeatability, outstanding stability, and broad linear range. The results detected by RAMP is consistent with results detected by Elecsys.