Relationship between plasma SP-A expression level and disease stage in silicosis patients / 上海预防医学

ObjectiveTo investigate the relationship between plasma surfactant protein⁃A （SP⁃A） expression level and silicosis progression， and to provide early evidence for exploring whether SP⁃A can be used as a biomarker for clinical monitoring of silicosis disease progression. MethodsWe recruited 187 silicosis patients in Guangdong Province hospital for occupational disease prevention and treatment between November， 2019 and November，2020. Their peripheral venous blood samples were collected for the plasma isolation. The level of pulmonary SP⁃A was detected by enzyme-linked immunosorbent assay. ResultsThere was a statistically significant difference in the level of SP⁃A among the silicosis groups （P<0.05）， and the plasma SP-A level of the silicosis patients in stage Ⅲ was higher than that in stage Ⅰ and stage Ⅱ （P<0.05）. Smoking had effect on plasma SP⁃A levels， Age， working years and drinking had no effect on plasma SP⁃A levels. ConclusionThe expression level of SP⁃A in the plasma of silicosis patients is increased， which has a certain correlation with the disease stage， and plays a certain early warning role in the occurrence and development of silicosis， and may be a potential biomarker for the diagnosis and prognosis of silicosis.

Clinical significance of Clara cell secreted protein 16 and pulmonary surfactant protein-A in early diagnosis of neonatal acute respiratory distress syndrome / 中国小儿急救医学

Objective:To investigate the clinical significance of changes of serum Clara cell secretory protein(CC16) and pulmonary surfactant protein A(SP-A) in neonates with acute respiratory distress syndrome(ARDS).Methods:The data of 30 neonates with ARDS who needed mechanical ventilation in neonatal intensive care unit of Xi′an Children′s Hospital from January 2016 to November 2018 were collected as observation group, including 12 cases in mild group, 10 cases in moderate group and 8 cases in severe group.The data of healthy newborns during the same period were taken as control group.The serum levels of CC16 and SP-A were detected by ELISA.The serum levels of CC16 and SP-A among different groups were compared.Results:The levels of serum CC16 and SP-A in ARDS group were (59.35±3.67)mg/L and(75.38±6.27)mg/L respectively, (11.26±1.32)mg/L and(18.15±2.69)mg/L in healthy group.The difference was significant( P<0.05). And the differences of serum CC16 and SP-A levels among different degree ARDS groups were significant( P<0.05). The levels of serum CC16 in mild, moderate and severe subgroup were(38.27±16.01)mg/L, (51.25±15.63)mg/L, (84.76±13.12)mg/L and SP-A were(47.02±7.18)mg/L, (73.12±7.98)mg/L, (96.45±12.50)mg/L, which increased with disease severity. Conclusion:Serum CC16 and SP-A are increased and correlated with the severity of neonatal ARDS, which may be used as the index for evaluating the severity of neonatal ARDS in the future.

Effects of CENP-A on invasion and migration of ovarian cancer cells by regulating PI3K/AKT/NF-κB signaling pathway / 中华内分泌外科杂志

Objective:To investigate the effects of centromere protein-A (CENP-A) on the invasion and migration of ovarian cancer (OC) cells and explore the related mechanism.Methods:OC cell line A2780 was cultured in vitro, and they were divided into Ng Group (Blank Control Group) , pcDNA group (negative transfection group:PCDNA vector plasmid) , pcDNA-CENP-A group (over-expression Group: pcDNA-CENP-A Vector Plasmid) and pathway inhibitor group (TRANSFECTION-CENP-A+ PI3K pathway inhibitor LY294002) . The cell proliferation was detected by CCK-8 method; the cell migration and invasion was detected by Scratch test and Transwell test; the expression of CENP-A, E-cadherin, N-cadherin and phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-kappa B (PI3K/AKT/NF-κB) pathway related proteins was detected by Western blot.Results:A2780 cells were successfully transfected. After 24 hours, with the extension of culture time, compared with that in NG group [ (0.50±0.07) , (0.72±0.11) , (0.99±0.14) ] and pcDNA group [ (0.55±0.08) , (0.78±0.12) , (1.02±0.15) ], the viability of A2780 cells in pcDNA-CENP-A group [ (0.78±0.12) , (1.03±0.15) , (1.67±0.25) ] and pathway inhibitor group [ (0.63±0.09) , (0.87±0.13) , (1.39±0.20) ] increased significantly ( P<0.05) , compared with that in the pcDNA-CENP-A group, the viability of A2780 cells in the pathway inhibitor group was significantly decreased ( P<0.05) , in a time-dependent manner. Compared with those in NG group [ (15.83±1.46) %, (105.32±15.78) individual] and pcDNA group [ (16.79±1.46) %, (108.98±16.35) individual], the migration rate [ (37.96±5.80) %, (25.15± 2.19) %] and invasion number [ (327.87±49.18) individual, 206.53±30.97) individual] of A2780 cells, protein expression of CENP-A, N-cadherin, Vimentin, p-PI3K/PI3K, p-AKT/AKT, NF-κB, interleukin (IL-1β) , tumor necrosis factor-α (TNF-α) in pcDNA-CENP-A group and pathway inhibitor group were significantly higher ( P<0.05) , the expression of E-cadherin was significantly lower ( P<0.05) ; compared with those in the pcDNA-CENP-A group, the migration rate and invasion number of A2780 cells, protein expression of CENP-A, N-cadherin, Vimentin, p-PI3K/PI3K, p-AKT/AKT, NF-κB, interleukin (IL-1β) , tumor necrosis factor-α (TNF-α) in pathway inhibitor group were significantly lower ( P<0.05) , and the expression of E-cadherin was significantly higher ( P<0.05) . Conclusion:Overexpression of CENP-A can promote the proliferation, invasion and migration of ovarian cancer cells, which may be achieved by activating PI3K/AKT/NF-κB signaling pathway.

Effect of first trimester maternal serum pregnancy associated plasma protein: a level on fetomaternal outcome

Background: Serum pregnancy-associated plasma protein-A (PAPP-A) levels fluctuate in continuation with the pregnancy and thus become an important standalone marker in monitoring the adverse outcomes that may occur in pregnancy.Methods: A prospective observational study was conducted in the department of obstetrics and gynaecology. A total of 240 pregnant women in their first trimester were included in the study. Serum PAPP-A levels were measured at 11-13+6week of gestation and were evaluated with respect to the feto-maternal outcome. The data was entered in MS excel spreadsheet and analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0.Results: The mean age of the study population was 27 years. Among the maternal pregnancy parameters, PIH, pre-term labor and Emergency LSCS were significantly associated with low (<0.5 MoM) Serum PAPP-A levels, P<0.05. All the fetal outcome measures: IUGR, IUD, low birth weight, SGA babies, prematurity and NICU admissions, were significantly associated with low (<0.5 MoM) Serum PAPP-A levels, p <0.05.Conclusions: Serum PAPP-A in the early pregnancy showed significant correlation with feto-maternal outcome. Thus, it has the potential to be used as a prognostic factor and in the management of adverse outcomes by increasing surveillance for pregnant women with high-risk factors.

Corrección de los múltiplos de la mediana de los biomarcadores del modelo de predicción de preeclampsia de la Fetal Medicine Foundation para población mexicana / Correction of the multiples of median of the biomarkers used in the Fetal Medicine Foundation's prediction model for preeclampsia in Mexican population

Resumen OBJETIVO: Calcular y ajustar los múltiplos de la mediana para el índice de pulsatilidad medio de las arterias uterinas, presión arterial media materna, factor de crecimiento placentario y proteína plasmática A asociada al embarazo, a fin de valorar el desempeño diagnóstico del modelo corregido de preeclampsia de la Fetal Medicine Foundation en población mexicana. MATERIALES Y MÉTODOS: Estudio de casos y controles anidado en una cohorte prospectiva efectuado en el Centro de Salud Dr. Galo Soberón y Parra entre el 1 de octubre de 2015 y el 30 de junio de 2016. Criterio de inclusión: pacientes con embarazo de 11-13.6 semanas. Criterio de exclusión: pacientes de riesgo no seleccionado, con embarazo único, entre 11 y 13.6 semanas calculadas por ecografía mediante longitud cráneo cauda. Criterio de eliminación: pacientes que abandonaron el estudio. Se evaluaron el índice de pulsatilidad medio de las arterias uterinas, la presión arterial media, los valores séricos del factor de crecimiento placentario y la proteína plasmática A asociada al embarazo. Se comparó la diferencia en la distribución de los biomarcadores entre la observada en población mexicana y la esperada según la formula original de la Fetal Medicine Foundation. Cuando la diferencia fue mayor a 0.2 múltiplos de la mediana, se utilizó la mediana del observado como coeficiente de ajuste a la fórmula original del esperado. RESULTADOS: De las 300 pacientes reclutadas, 292 concluyeron el estudio. La media de semanas de embarazo al momento del tamizaje fue de 12.4 (desviación estándar 0.72). La prevalencia de preeclampsia fue de 4.5% (13 de 292). Se encontraron diferencias importantes en la distribución de múltiplos de la mediana para el índice de pulsatilidad medio de las arterias uterinas, factor de crecimiento placentario y proteína plasmática A asociada al embarazo. Posterior a la corrección de los biomarcadores, la sensibilidad, falsos positivos y área bajo la curva del modelo ajustado para detectar cualquier preeclampsia fue de 92% (12 de 13), 5.7% (16 de 279) y 93.3%, respectivamente. CONCLUSIONES: La distribución de los múltiplos de la mediana en población mexicana es distinta para los biomarcadores: factor de crecimiento placentario, proteína plasmática A asociada al embarazo e índice de pulsatilidad medio de las arterias uterinas. El ajuste de estos biomarcadores para población mexicana resulta en un buen desempeño diagnóstico del modelo de preeclampsia.

Abstract OBJECTIVE: Calculate and adjust the multiples of the median (MoMs) for the mean pulsatility index of uterine arteries (IPm Aut), mean arterial pressure (PAM), placental growth factor (PlGF) and plasma protein associated with pregnancy (PAPP-A), in order to assess the diagnostic performance of the corrected preeclampsia model of the fetal medicine foundation in the Mexican population. MATERIALS AND METHODS: Case-control study nested in a prospective cohort conducted at the "Dr. Galo Soberón y Parra "from October 1, 2015 - June 30, 2016. Patients with pregnancy of 11-13.6 weeks were included, multiple pregnancies or older than 14 weeks were excluded and patients with medication intake prior to pregnancy; Patients who decided to leave the study were eliminated. Autm IPm, PAM, PlGF and PAPP-A serum values were evaluated. The difference in the distribution of biomarkers between that observed in the Mexican population and that expected was compared according to the original formula of the Fetal Medicine Foundation. When the difference was greater than 0.2 MoMs, the median observed was used as an adjustment coefficient to the original expected formula. RESULTS: Of the 300 patients recruited, 292 concluded the study. The average gestational age at the time of screening was 12.4 weeks (standard deviation [SD] 0.72). The prevalence of preeclampsia was 4.5% (13/292). Important differences were found in the distribution of multiples of the median (MoMs) for IPm Aut, PlGF and PAPP-A. After correction of the biomarkers, the sensitivity, false positives and area under the curve (AUC) of the model adjusted to detect any preeclampsia was 92% (12/13), 5.7% (16/279) and 93.3%, respectively . CONCLUSIONS: The distribution of MoMs in the Mexican population is different for the PlGF, PAPP-A and IPm Aut biomarkers. The adjustment of these biomarkers to the Mexican population results in a good diagnostic performance of the preeclampsia model.

Correlation between polymorphisms of surfactant protein A1 rs1059047 and rs1136450 and respiratory distress syndrome in Mongolian premature infants / 中华急诊医学杂志

Objective To study the correlation between polymorphisms of surfactant protein A1 rs1059047 and rs1136450 and respiratory distress syndrome (RDS) in Mongolian premature infants in Inner Mongolia.Methods Totally 50 Mongolian RDS premature infants in our ward were recruited as the case group (33 males and 17 females),and another 50 Mongolian non-RDS premature infants with same ethnicity,same sex and gestational age were served as the control group (29 males and 21 females).Single nucleotide polymorphisms of SP-A1 rs1059047 and,rs1136450 and allele haploids (6A,6A2,and 6A3) were detected by polymerase chain reaction-single strand conformation polymorphism gene detection technology and were compared between the case and control groups.Results Threegenotypes,CC,TT,CT were detected in the case and control groups at rs1059047,all ofwhich were mainly TT genotype.There was no significant difference in genotype frequency between the two groups (x2=1.429,P ＞ 0.05).Two genotypes,CG and GG,were detected in the case and control groups at rsl 136450,and CG was the dominant genotype.There was no significant difference in genotype frequency between the two groups (x2=1.624,P＞0.05).The distribution frequency of SP-A1 allele haploids (6A,6A2,6A3) in the case group was 36％,68％ and 42％,respectively,and 62％,46％ and 50％ in the control group,respectively.There was no significant differencein the frequency of allele haploid 6A3 between the two groups (x2=0.502,P＞0.05);but there was a significantly difference in the frequency of allele haploids (6A,6A2) between the two groups (x2=6.763,4.937,P＜0.05).Conclusions The alleles and allele fiequency of SP-A1 (rs1059047,rs1136450) were not associated with RDS in Mongolian premature infants.However,SP-A1 allele haploid 6A2 is the susceptible gene for RDS in Mongolian premature infants,and haploid 6A is the protective gene.

Reference centile charts of first-trimester aneuploidy screening & Doppler parameters for Indian population

Background & objectives: The risk estimation for foetal aneuploidies in the first trimester of pregnancy uses reference curves based on western data. The objective of this study was to construct the reference curves of first-trimester foetal aneuploidy screening parameters for the Indian women. Methods: Cross-sectional data were obtained from 1204 singleton pregnancies between the crown-rump length (CRL) of 40-84 mm. Linear regression models were constructed; the mean, median and standard deviation were derived as a function of CRL. Results: The mean value of CRL was 61.3 mm. The regression analysis showed a significant correlation between all variables and CRL (P< 0.001). There was a positive correlation of CRL with nuchal translucency (NT) (y=0.010x+0.629, R2=0.116) and pregnancy-associated plasma protein-A (PAPP-A) (y=0.107x?1.079, R2=0.173), whereas inverse correlation was seen with free ?-human chorionic gonadotropin (?-hCG) (y=?0.409x+75.025, R2=0.018) and Doppler parameters pulsatility index (PI) (y=?0.008x+1.924 R2=0.053). The centile charts of NT, PAPP-A, free ?-hCG and uterine artery (Ut A) Doppler PI were constructed. Interpretation & conclusions: The reference centile charts of first trimester aneuploidy screening along with Doppler parameters were derived in Indian pregnant women. These centile charts may be used as a reference for clinical use in Indian population.

Relationship between surfactant associated protein-A in bronchoalveolar lavage fluid and lung function in children with refractory mycoplasma pneumoniae pneumonia / 新乡医学院学报

Objective To investigate the relationship between surfactant associated protein-A(SP-A) in bronchoalveolar lavage fluid(BLAF) and lung function in children with refractory mycoplasma pneumoniae pneumonia(RMPP).Methods Thirty children with RMPP were selected from January 2015 to December 2016 in the People's Hospital of Hebi City.The partial pressure of oxygen in artery (PaO2),partial pressure of carbon dioxide in artery (PaCO2),forced expiratory volume in one second(FEV1) and forced vital capacity (FVC) of the children were detected at acute and convalescent periods.The BALF was collected by bronchoalveolar lavage,and the level of SP-A in BALF was detected by enzyme linked immunosorbent assay.Results The level of SP-A in BALF of children with RMPP at ac ute and convalescent period was (3.63 ± 0.09) and (5.86 ± 0.17)mg · L-1 respectively,the level of SP-A in BALF of children with RMPP at acute phase was significantly lower than that at convalescent period(t =-63.499,P ＜ 0.05).The PaO2 and PaCO2 in children with RMPP at acute phase were (49.25 ±7.32) and (47.16 ±6.48)mmHg respectively,and they were (76.54 ±6.48) and (36.20 ± 5.61)mmHg respectively at convalescent period;the PaO2 in children with RMPP at acute phase was significantly lower than that at convalescent period (t =-15.289,P ＜ 0.05),and the PaO2 in children with RMPP at acute phase was significantly higher than that at convalescent period(t =7.004,P ＜ 0.05).The FEV1,FVC and FEV1/FVC in RMPP children at acute phase were (1.36 ±0.67),(1.68 ± 0.31) L and 69.85 ± 8.34 respectively;and they were (1.89 ± 0.58),(1.99 ± 0.53) L and 87.32 ± 9.52 respectively at convalescent period;the FEV1,FVC and FEV1/FVC in RMPP children at acute phase were significantly lower than those at convalescent period(t =-3.276,-2.765,-7.560;P ＜ 0.05).The level of SP-A in BALF of children with RMPP was positively correlated with PaO2 (r =0.921 6,P ＜ 0.05),but there was no significant correlation between SP-A level and PaCO2 (r =1.211 4,P ＜ 0.05).The level of SP-A in BALF was positively correlated with FEV1,FVC and FEV1/FVC (r =0.831,0.905,0.803;P ＜ 0.05).Conclusion The level of SP-A in BALF was positively correlated with lung function of children with RMPP.The detection of SP-A level in BALF is helpful to assess the lung function and pathogenetic condition of children with RMPP.

Clinical value of surfactant protein-A in exudate pleural effusion / 中南大学学报(医学版)

Objective:To evaluate the clinical value of surfactant protein-A (SP-A) in exudate pleural effusion (EPE).Methods:This clinical study was prospective,observational and cross-sectional.Two hundred and fifteen patients with pleural effusion were divided into the transudate pleural effusions (TPE) group and the EPE group.TPE patients served as the control group.The concentrations of pleural effusions SP-A (SP-Apl) and serum SP-A (SP-Ase) were measured by ELISA,and receiver operator characteristic (ROC) curve and multivarate Cox analysis of SP-A was analysed for its clinical value.Results:SP-Apl concentrations in the EPE group were significantly higher than that in the TPE group [(189.8±43.4) ng/mLvs (22.3±5.1) ng/mL,P＜0.01];SP-Ase concentrations in the EPE group were higher than that in the TPE group [(78.9±11.3) ng/mL vs (25.8±12.4) ng/mL,P＜0.05];SP-Apl concentrations were significantly higher than the concentrations of SP-Ase in the EPE group (P＜0.01).In EPE group,SP-Apl and SP-Ase concentration in the patients with primary lung adenocarcinomas were the highest.The cut off value of SP-Apl concentrations was more than 484.5 ng/mL,yielding a 85.4％ sensitivity and 95.2％ specificity for diagnosing primary lung adenocarcinomas,with an area under the curve (AUC) of 0.943 (95％ CI 0.852 to 0.934,P＜0.01);when SP-Ase concentration was more than 84.2 ng/mL,it yielded a 76.4％ sensitivity and 94.3％ specificity for diagnosing primary lung adenocarcinomas,with an AUC of 0.910 (95％ CI 0.921 to 0.953,P＜0.01).Conclusion:While SP-Apl concentration is more than 484.5 ng/mL and/or SP-Ase concentration is more than 84.2 ng/mL,it may be helpful for the diagnosis of primary lung adenocarcinomas with the usage ofpleural effusion.

Predictive value of pregnancy-associated plasmaprotein-A and global registry of acute coronary events risk score on major adverse cardiac events in patients with acute myocardial infarction / 中国介入心脏病学杂志

Objective To investigate the predictive value of pregnancy-associated plasmaprotein-A (PAPP-A) and GRACE risk score for death and nonfatal myocardial infarction (combined endpoint) in AMI patients.Methods All AMI patients hospitalized in our department during July 2011 to July 2015 were included consecutively in this prospective study.Plasma PAPP-A were measured at admission.GRACE risk score was acquired with the application of GRACE risk score calculator.Patients were followed up for at least 1 year for any nonfatal myocardial infarction or MACE.Kaplan Meier survival study was analysed according to PAPP-A and GRACE score risk stratification respectively.A cutoff value of 3.0 ng/ml of PAPP-A was chosen from pilot work in this cohort.Results A total of 220 patients were enrolled in the study.The death and nonfatal myocardial infarction during follow-up were significantly higher in patients with PAPP-A≥3.0 ng/ml compared to patients with PAPP-A<3.0 ng/ml (15.7% vs.6.0%, log-rank χ2=5.684, P=0.017).The area under ROC curve of PAPP-A was 0.796(95%CI 0.696-0.896, P<0.01) and the ROC curve of PAPP-A GRACE risk stratification was 0.715 (95%CI 0.567-0.863,P<0.01).Subgroup analysis showed that death and nonfatal myocardial infarction during follow-up was significantly higher in patients with PAPP-A≥3.0 ng/ml compared to patients with PAPP-A<3.0 ng/ml in intermediate and low risk group by GRACE risk stratifcation (log-rank χ2=14.63,P<0.001).Conclusions PAPP-A could predict mortality and nonfatal myocardial infarction in patients with AMI.PAPP-A combined with GRACE risk score can better predict outcome than GRACE risk score alone in intermediate and low risk patients by GRACE risk stratifcation.

Asociación entre el sistema IGF y PAPP-A en ateroesclerosis coronaria / Association between IGF system and PAPP-A in coronary atherosclerosis

Resumen La aterosclerosis es una enfermedad que involucra múltiples mecanismos fisiopatológicos cuyo conocimiento no se ha dilucidado por completo. Con frecuencia, los avances científicos sobre la fisiopatología aterogénica generan que a diversas moléculas no consideradas previamente en el panorama de dicha enfermedad se les atribuyan acciones sobre el inicio o progresión de la misma. Un ejemplo representativo es el estudio de un nuevo mecanismo involucrado en el proceso aterogénico, consistente en la asociación entre el sistema de factores de crecimiento similares a la insulina (IGF) y la proteína plasmática A asociada al embarazo (PAPP-A). El sistema IGF es una familia de péptidos compuesto por 3 hormonas peptídicas, 4 receptores transmembranales y 6 proteínas transportadoras. El factor de crecimiento similar a la insulina tipo 1 (IGF-1) es el principal ligando del sistema IGF involucrado en la aterosclerosis coronaria y ejerce sus efectos mediante la activación del receptor IGF-1R en células de músculo liso vascular de las arterias coronarias o en macrófagos de placas ateroscleróticas. En células de músculo liso vascular promueve la migración y previene la apoptosis aumentando la estabilidad de la placa, y en macrófagos disminuye el transporte reverso de colesterol propiciando la formación de células espumosas. La regulación de la biodisponibilidad de IGF-1 en el endotelio se lleva a cabo por las proteasas de proteínas IGFBP, principalmente por la PAPP-A. En la presente revisión se abordan los mecanismos involucrados entre el sistema IGF y la PAPP-A en aterosclerosis coronaria con énfasis en los efectos moleculares producidos en células de músculo liso vascular y en macrófagos.

Abstract Atherosclerosis is a condition that involves multiple pathophysiological mechanisms and whose knowledge has not been fully elucidated. Often, scientific advances on the atherogenic pathophysiology generate that molecules not previously considered in the scene of this disease, were attributed actions on the onset or progression of it. A representative example is the study of a new mechanism involved in the atherogenic process, consisting of the association between the insulin-like growth factor (IGF) system and pregnancy-associated plasma protein-A (PAPP-A). Insulin-like growth factor system is a family of peptides that include 3 peptide hormones, 4 transmembrane receptors and 6 binding proteins. Insulin-like growth factor-1 (IGF-1) is the main ligand of the IGF system involved in coronary atherosclerosis. IGF-1 exerts its effects via activation of the IGF-1R receptor on vascular smooth muscle cells or macrophages. In vascular smooth muscle cells promotes migration and prevents apoptosis which increases plaque stability while in macrophages reduces reverse cholesterol transport leading to the formation of foam cells. Regulation of IGF-1 endothelial bioavailability is carried out by IGFBP proteases, mainly by PAPP-A. In this review, we address the mechanisms between IGF system and PAPP-A in atherosclerosis with emphasis on molecular effects on vascular smooth muscle cells and macrophages.

Relationship between serum PAPP-A expression and gene polymorphism with severity of coronary lesions in patients with coronary heart disease / 重庆医学

Objective To investigate the relationship between serum pregnancy associated plasma protein A (PAAA‐A) ex‐pression and gene polymorphism with the severity of coronary lesions in the patients with coronary heart disease (CHD) .Methods Ninety‐eight patients with CHD in the Nanyang Municipal Central Hospital were selected as the observation group and divided into single vessel lesion group and multiple vessel lesion group according to coronary angiographic results .Ninety‐eight individuals un‐dergoing healthy physical examination were selected as the control group .The venous blood was collected at the visiting hospital in the observation group and at the physical examination in the control group for detecting the serum PAPP‐A protein level by ELISA .PAPP‐A gene and IVS6+ 95 polymorphism were analyzed by adopting polymerase chain reaction restriction fragment length polymorphism(PCR‐RELP) .Results Compared with the control group ,peripheral blood PAPP‐A protein level in the obser‐vation group was significantly increased(P<0 .05) ,moreover the PAPP‐A protein level in the multiple vessel lesion group was sig‐nificantly higher than that of the single vessel lesion group (P<0 .05) .The peripheral blood PAPP‐A level was positively correlated with the severity of CHD .Three genotypes existed in PAPP‐A gene IVS6+95 locus ,including CG heterozygous ,homozygous CC and GG homozygous type .The CC homozygous allele frequency in the patients with multiple vessel lesion was higher than that in the patients with single vessel lesion (P<0 .05) .Conclusion The PAPP‐A protein level and IVS6+95 polymorphism have a close relation with the severity of coronary lesions in patients with CHD .CC genotype may be one of genetic susceptibility gene markers in the patients with CHD .

Serum levels and clinical signiifcance of IGF1, IGFBP-4 and PAPPA in non-small cell lung cancer / 中国癌症杂志

Background and purpose:It is increasingly focused on that insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 4 (IGFBP-4) effect cell proliferation, differentiation and apoptosis of tumor cells, and pregnancy-associated plasma protein-A (PAPPA) plays an important role in IGF-1-dependent IGFBP-4 protease mechanism that regulats tumor cells' growth. This study aimed to investigate the serum levels and clinical signiifcance of IGF-1, IGFBP-4, and PAPPA in patients with non-small cell lung cancer (NSCLC). Methods:IGF-1, IGFBP-4, and PAPPA plasma levels were measured by enzyme-linked immunosorbent assay from 82 patients with NSCLC and 40 control subjects, then the correlations between variables were assessed by Spearman correlation analysis, and associations between the IGFs variables and lung cancer risk were calculated through the odds ratio (OR) and its 95%conifdence interval (CI) with the use of unconditional logistic regression analysis. Results:Serum levels of IGF-1, IGFBP-4 and PAPPA in NSCLC patients were signiifcantly higher than those in the control group(P<0.05). There was a signiifcant positive correlation between the serum IGF-1 levels and PAPPA levels (r=0.835,P=0.000), and a negative correlation with IGFBP-4 levels (r=-0.612,P=0.000). IGFBP-4 and PAPPA levels were negatively correlated(r=-0.673, P=0.000). High plasma levels of IGF-1(OR=2.28, 95%CI: 1.25-4.36,P=0.008) and PAPPA (OR=1.64, 95%CI: 0.89-3.01,P=0.046)were associated with an increased risk of lung cancer, however high plasma levels of IGFBP-4(OR=0.54, 95%CI:0.30-1.01,P=0.047)were associated with reduced risk of lung cancer. Conclusion:To detect IGF-1, IGFBP-4 and PAPPA in serum in NSCLC patients is meaningful for the clinical auxiliary diagnosis and biology behavior prediction of NSCLC. And further study of signal transduction pathways of IGFs with the occurrence and development of NSCLC is a meaningful research direction.

Proteína plasmática A asociada al embarazo y fracción β de gonadotrofina coriónica humana en pacientes con resultados materno y perinatal adverso: informe preliminar / Plasma protein associated with pregnancy and β fraction human chorionic gonadotropin results in patients with adverse maternal and perinatal: preliminary report

Objetivo: Evaluar el comportamiento de marcadores bioquímicos: proteína plasmática asociada al embarazo (PAPP-A) y fracción β de la hormona gonadotrofina coriónica (β hCG) con resultado materno y perinatal adverso en el Hospital “Dr. Adolfo Prince Lara”. Métodos: Estudio prospectivo, comparativo en 35 gestantes con embarazos simples entre las 11 y 13 semanas + 6 días y resultado del embarazo conocido. Se realizó tamizaje combinado: traslucencia nucal, hueso nasal, ductus venoso, longitud craneocaudal y marcadores bioquímicos (PAPP-A y β -hCG). Se determinó la concentración de PAPP-A y β -hCG y sus resultados se expresaron en MoM. Variables cuantitativas fueron expresadas en media y desviación estándar (DE), cualitativas en porcentajes y se compararon estas variables entre el grupo de gestantes con resultado materno perinatal normal (RMPN) y adverso (RMPA) con la prueba U de Mann-Whitney. Resultados: 71 % tuvieron un RMPN y 29 % RMPA. No se encontraron diferencias entre los grupos respecto a edad materna, peso materno, IMC, paridad, presión arterial. La PAPP-A expresado en MoM presentan un valor más alto en las embarazadas que tuvieron un RMPA (1,07 vs 1,43) siendo estadísticamente significativo, los valores de β-HCG tuvieron valores más altos (0,60 vs 0,76) entre el grupo con RMPA en relación al grupo con RMPN sin llegar a la significancia estadística. Conclusión: Valores de la MoM PAPP-A difieren en las embarazadas con RMPA de aquellas con resultado normal, pero con valores mayores en las primeras, contrario a lo encontrado en la mayoría de las publicaciones estudiadas, iguales hallazgos con la β-hCG. Se debe profundizar en estos estudios para verificar los resultados encontrados.

Objective: To evaluate the behavior of biochemical markers PAPP-A and β hCG with adverse pregnancy and perinatal outcomes. Methods: Prospective, comparative study in 35 pregnant women with singleton pregnancies between 11 and 13 weeks + 6 days and outcome of pregnancy known. Nuchal translucency, nasal bone, ductus venosus, rump length and biochemical markers (PAPP-A and β-hCG) combined screening was performed. The concentration of PAPP-A and β-hCG was determined and the results were expressed in MoM. Quantitative variables were expressed as mean and standard deviation (SD), and these percentages qualitative variables between the group of pregnant women with a normal perinatal maternal outcome (NPMO) and adverse (AMPO) with the U Mann-Whitney test were compared. Setting: Hospital “Dr. Adolfo Prince Lara”. Results: 71 % had a NPMO and 29 % had an AMPO. No differences between the groups in respect of maternal age, maternal weight, BMI, parity, blood pressure were found. PAPP-A MoM have expressed a higher value in pregnant having an AMPO (1.07 vs 1.43) were statistically significant, the values of β-HCG had higher values (0.60 vs 0.76) between the group with AMPO relative to NMPO group without reaching statistical significance. Conclusion: MoM values of PAPP-A differ in pregnant with AMPO than in those with normal results, but with higher values in the first opposite to that found in most of the studied publications, the same findings with β-hCG. Thus, it should look into these studies to verify the results found.

Effect of salvianolate injection on serum levels of pregnancy associated plasma protein A , brain natriuretic peptide and high sensitively C-reactive protein in elderly patients with acute myocardial infarction / 中华老年医学杂志

Objective To observe the effects of salvianolate injection on blood levels of high sensitively C-reactive protein (hs-CRP),pregnancy associated plasma protein-A (PAPP-A) and brain natriuretic peptide (BNP) in elderly patients with acute myocardial infarction.Methods The elderly patients with AMI (AMI group,n=160) and healthy controls (control group.n=30) were enrolled in this study and their blood concentrations of PAPP A,hs CRP and BNP were detected before and two weeks after treatment.The elderly patients in AMI group were randomized into conventional treatment group (n =80) and salvianolate group (n =80).Results The levels of PAPP-A,hs-CRP and BNP were significantly higher in AMI patients [(12.88±2.56) mg/L,(20.13 ±5.35) mU/L,(412.0±69.5) ng/L,respectively] than in healthy subjects[(1.20±0.88) mg/L,(1.90±0.46) mU/L,(89.0±5.6) ng/L,respectively] (t=24.670,3.780,11.939,respectively,P ＜0.01).But,before treatment there were no significant differences in the levels of PAPP-A,hs-CRP and BNP between the AMI group and control group (t=0.864,0.712,0.985,all P＞0.05).After two weeks of treatment,as compared with control group,AMI group showed that the serum concentrations of PAPP-A,hs-CRP and BNP were decreased significantly (P＜0.05).The levels of PAPP A,hs-CRP and BNP were (3.83±1.20) mg/L,(1.33±0.38) mU/L,(105.0±31.2) ng/L in salvianolate group and (5.71± 1.93) mg/L,(1.81±0.72) mU/L,(150.0±36.7) ng/L in conventional treatment group respectively,and the decrements in levels of PAPP-A,hs CRP and BNP were greater in the former than in the latter(t=7.399,5.273,8.356,respectively,all P＜0.05).Conclusions The dynamic serum concentrations of PAPP-A,hs CRP and BNP can be used as clinical indexes for the prognosis of acute myocardial infarction.Salvianolate injection can significantly decrease the serum levels of PAPP A,hs CRP and BNP.The salvianolate injection may have anti inflammatory effect and improve cardiac function in elderly patients with acute myocardial infarction,but the mechanism is still to be further discussed.

The relationship between serum pregnancy associated plasma protein A level and pregnancy outcomes in early pregnancy / 中国医师进修杂志

Objective To explore the relationship between pregnancy associated plasma protein A (PAPP-A) and threatened abortion,whether low level of PAPP-A in early pregnancy can be used as indicators to predict the pregnancy outcomes.Methods The level of serum PAPP-A was measured by double antibody sandwich enzyme-linked immunosorbent assay in 110 cases with threatened abortion (threatened abortion group) and 131 cases with normal intrauterine pregnancy (control group),and track to 20 weeks pregnant.Results The serum PAPP-A multiple of median (MOM) value was 1.02 ± 0.15 in control group,0.98 ± 0.17 in threatened abortion group,and there was no significant difference(P ＞ 0.05).In threatened abortion group,90 cases of spuc success,the serum PAPP-A MOM value was 1.03 ± 0.11,20 patients of spuc failure,the serum PAPP-A MOM value was 0.73±0.21,and there was significant difference (P ＜ 0.01).There was no significant difference in the serum PAPP-A MOM value between control group and the spuc success of threatened abortion group (P ＞ 0.05).Conclusion Pregnant women with PAPP-A levels embryonic development is closely related to the good,as one can predict miscarriage in pregnant women with threatened abortion outcome evaluation.

The early diagnosis value of the serum surfactant protein a in critically ill acute lung injury of HFMD / 重庆医学

Objective To explore the early diagnosis clinical value of the serum surfactant protein-A (SP-A) against acute lung injury on HFMD (hand ,foot and mouth disease) in critically ill .Methods 60 cases of HFMD were selected in Xingtai People′s Hospital from August 2010 to December 2011 ,and they were divided into three groups .20 were ordinary cases ,28 were severe cases and 12 were critical cases(4 cases dead) .According to PaO2/FiO2 of ALI ,3 of critical cases (PaO2/FiO2 >300 mm Hg) were put into the non lung injury group and 9 (PaO2/FiO2 ≤300 mm Hg) were put into the lung injury group .Besides ,15 cases of healthy children were selected as the control group .The changes of the serum SP-A levels in these children were detected through ELISA methods after 24 h and 72 h .Results Contrasting the serum SP-A levels in the ordinary and severe groups separately with the ones in control group ,there was no statistical significance(P>0 .05) and so was contrasting the serum SP-A levels in the ordinary group with the ones in the severe group ,and the serum SP-A levels in the critical group after 24 h was significantly higher than the ordina-ry and severe groups (P0 .05) ,con-trasting with ones in the control group ;but the serum SP-A levels in the lung injury group after 24 h were significantly higher than ones in the control group and in the non lung injury group (P<0 .05) .Conclusion Detection of the serum SP A has clinical value of the early diagnosis of acute lung injury on HFMD in critically ill ,which is beneficial to guide the clinical treatment .Meanwhile , it can reduce the mortality rate and the sequela ,and help to diagnose the condition of acute lung injury and treat it .

Regulação diferencial da deubiquitinase A20 em tecido adiposo de obesos: potencial envolvimento na regulação da PGC1a / A20 deubiquitinase controls PGC-1a expression in the adipose tissue

A proteína PGC1α é um co-ativador de transcrição gênica que desempenha papel importante na regulação de uma série de fenômenos metabólicos que compreendem desde o controle da termogênese e mitocondriogênese até a regulação da secreção de insulina e a produção hepática de glicose. Como vários dos fenômenos biológicos controlados direta ou indiretamente pela PGC1α tem importância vital, a regulação dos níveis de PGC1α nos tecidos deve ser finamente ajustada. Nos últimos anos, inúmeros estudos exploraram os mecanismos envolvidos com o controle da expressão gênica e tradução da PGC1α. Entretanto, apenas alguns poucos estudos avaliaram a degradação da mesma. Um dos mais importantes mecanismos envolvidos com a regulação funcional e da meia-vida de proteínas é a ubiquitinação, que pode direcionar proteínas alvo ao proteassoma para degradação ou a outras modificações pós-traducionais. O objetivo do presente estudo foi avaliar a participação de uma proteína com atividade deubiquitinase e ubiquitina ligase, a A20, na manutenção da homeostase do tecido adiposo de animais submetidos à dieta rica em gordura e voluntários humanos magros e obesos antes e após cirurgia de redução de peso. Foram utilizados o tecido adiposo branco visceral e subcutâneo e o tecido adiposo marrom de camundongos Swiss machos submetidos a 16 semanas de dieta hiperlipídica e o tecido adiposo subcutâneo de voluntários magros e obesos antes e após a cirurgia bariátrica. Esses tecidos foram avaliados quanto ao conteúdo protéico e expressão gênica da proteína A20, e sua associação com a PGC1α por imunoprecipitação e imunofluorescência, bem como a ubiquitinação desta última. Os resultados obtidos a partir do tecido adiposo de humanos mostram uma diminuição na expressão da proteína A20 nos pacientes antes e após a cirurgia bariátrica com relação aos voluntários magros.

Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α) plays an important role in whole body metabolism and, particularly in glucose homeostasis. Its expression is tightly regulated and, small variations in tissue levels can have a major impact in a number of physiological and pathological conditions. Recent studies have shown that the ubiquitin/proteasome system plays a role in the control of PGC-1α degradation. Here we evaluated the interaction of PGC-1α with the protein A20, which plays a dual-role in the control of the ubiquitin/proteasome system acting as a deubiquitinase and as an E3 ligase. We employed immunoprecipitation, quantitative real-time PCR and immunofluorescence staining to evaluate PGC-1α, A20, PPARγ and ubiquitin in the adipose tissue of humans and mice. Our results show that, in distinct sites of the adipose tissue A20 binds to PGC-1α. At least in the subcutaneous fat of humans and mice the levels of PGC-1α decrease during obesity, while its physical association with A20 increases. The inhibition of A20 leads to a reduction of PGC-1α and PPARγ expression, suggesting that A20 acts as a protective factor against PGC-1α disposal. Thus, we provide evidence that mechanisms regulating PGC-1α ubiquitination are potentially involved in the control of the function of this transcriptional co-activator.

Teste de ELISA indireto para diagnóstico sorológico de leishmaniose visceral em canídeos silvestres / Indirect ELISA for the serological diagnosis of visceral leishmaniasis in wild canids

Na América do Sul, alguns canídeos silvestres são considerados reservatórios naturais da Leishmania chagasi. A resposta imunológica desses animais à Leishmania é pouco conhecida, havendo a necessidade de métodos diagnósticos adequados para esse fim. No presente estudo, é descrita a padronização do ensaio imunoenzimático indireto (ELISA) para o diagnóstico sorológico de leishmaniose visceral em canídeos silvestres brasileiros. Foram estudadas amostras de soro e plasma de 12 canídeos cativos: sete lobos-guará (Chrysocyon brachyurus), três raposinhas (Lycalopex vetulus) e dois cachorros-do-mato (Cerdocyon thous). As amostras de um C. brachyurus e uma L. vetulus, cativos em área endêmica para LV, que apresentavam doença clínica e positividade em testes de Imunofluorescência Indireta e Reação em Cadeia de Polimerase, foram utilizadas como controles positivos. Foram comparados os conjugados anti-IgG de cão e proteína A, ambos ligados a peroxidase, cujos testes detectaram quatro (04/12) e três (03/12) C. brachyurus soropositivos para anticorpos anti-Leishmania sp., respectivamente. As médias das densidades ópticas (DOs) das amostras negativas foram nitidamente mais baixas do que as médias das DOs dos positivos tanto no ELISA com anti-IgG de cão (4,8 vezes) como com proteína A (15,5 vezes). Os soros de três C. brachyurus positivos no ELISA indireto foram avaliados por Western blotting e identificaram 22 bandas, sendo imunodominantes as de peso molecular de 19, 22, 24, 45 e 66 kDa. Os testes ELISA com a proteína A e o conjugado anti-IgG de cão apresentaram respectivamente concordância excelente (Kappa = 1; p<0,001) e moderada (Kappa = 0,8; p<0,0015), com o Western blotting. Ambos foram, portanto, considerados adequados a avaliações de triagem de animais cuja resposta humoral de anticorpos indica contato com o parasito, úteis para subsidiar estudos para adequação de metodologias específicas para os canídeos silvestres.

In South America, some wild canids are considered natural reservoirs of Leishmania chagasi. The immunological response of wild canids to Leishmania is not well understood, and the development of diagnostic methods is necessary for such purpose. In the present study, the standardization of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of visceral leishmaniasis (VL) in Brazilian species of wild canids is described. Serum and plasma samples from 12 captive wild canids were studied: seven from maned wolves (Chrysocyon brachyurus), three from hoary foxes (Lycalopex vetulus), and two from crab-eating foxes (Cerdocyon thous). Samples from C. brachyurus and L. vetulus, both captive in an endemic area for VL, presenting clinical disease and positivity in Indirect Immunofluorescence Reaction and Polymerase Chain Reaction tests were used as positive controls. The antibody anti-dog IgG and Protein A, both conjugated with horseradish peroxidase, were compared in indirect ELISA tests which detected four (04/12) and three (03/12) seropositive C. brachyurus for anti-Leishmania antibodies, respectively. The ELISA tests were able to clearly distinguish negative from positive samples, as the mean optical density (OD) of the negative samples was 4.8 and 15.5 times lower than those of the positive ones either using anti-dog IgG and Protein A, respectively. Samples from three ELISA - positive C. brachyurus were analyzed by Western blotting and identified immunodominant bands of 19, 22, 24, 45 and 66 kDa, among 22 protein bands detected. The ELISAs with protein A and anti-dog IgG showed respectively excellent (Kappa = 1.0; p<0.001) and moderate (Kappa = 0.8; p<0.0015) agreement with the Western blotting assay. The ELISA tests showed to be adequate for screening studies to identify antibody responses, thus indicating contact with Leishmania infection by wild canids.

Effect of hyperoxia on A549 cells suppressed with surfactant protein-A suppressed by small RNA interference-mediated gene silencing / 中华实用儿科临床杂志

Objective To explore the effect of hyperoxia on A549 cells suppressed with surfactant protein A (SP-A) suppressed by small interference RNA(SiRNA)-mediated gene silencing,and discuss the function of SP-A in hyperoxic lung injury.Methods A549 cells were gained by serial sub cultivation in vitro and randomly divided into 2 groups,silenced of SP-A group and the control group.A549 cells were transfected with synthetic SP-A sequence-specific SiRNA by Lipofectamine 2000,continuously exposed to hyperoxia(950 mL/L 02,50 mL/L CO2).After exposure to hyperoxia for 48 hours,72 hours and 96 hours,total protein and culture supernatant were gained.SP-A protein was detected by Western-blot,the capacity of proliferation was detected by methyl thiazolyl tetrazolium,and thiobarbituric acid colorimetric method was used to detect the malondialdehyde (MDA) in culture supernatant.Results Sequence-specific SiRNA targeted SP-A2 and significantly down-regulated its expression in A549 cells.Compared with the control group in hyperoxia,the expression of SP-A significantly decreased after 48 hours,72 hours in the silenced group (all P ＜ 0.05),and the capacity of proliferation in A549 cells silenced by SP-A were obviously decreased after 48 hours,72 hours and 96 hours(all P ＜0.05).But there was no significant difference in the MDA in culture supernatant between 2 groups(all P ＞ 0.05).Conclusions The capacity of resisting hyperoxia decreased in A549 cells silenced by SP-A,which indicates that SP-A can protect hyperoxic lung injury.