Application value of BIS and S100β combined with Copeptin in patients with acute severe carbon monoxide poisoning / 中华劳动卫生职业病杂志

Objective: To explore the application value of bispectral index(BIS) , specific protein 100β(S100β) combined with Copeptinin patients with acute severe carbon monoxide poisoning (ASCMP). Methods: A total of 256 patients with acute carbon monoxide poisoning admitted to Hengshui People's Hospital from June 2018 to June 2020 were collected, and they were divided into 30 mild cases, 40 moderate cases and 186 severe cases according to the degree of poisoning. Among them, patients with severe carbon monoxide poisoning were divided into a poor prognosis group (20 cases) and a good prognosis group (166 cases) according to whether adverse events occurred. The changes of creatine kinase isoenzyme (CK-MB) , N-terminal precursor B-type brain natriuretic peptide (NT-proBNP) , BIS, S100β, and Copeptin in poisoned patients were measured. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the significance of relevant indicators for ASCMP patients. Results: Compared with the mild-to-moderate group, CK-MB, NT-proBNP, S100β, Copeptin increased, and BIS value decreased in the severe group (P< 0.05). 24 hours after admission, compared with the good prognosis group, CK-MB, NT-proBNP, S100β, Copeptin in the poor prognosis group increased, and the BIS value decreased (P<0.05). In the poor prognosis group, CK-MB, NT-proBNP, S100β, and Copeptin at 72 hours after admission were all lower than those at 24 hours after admission, and the BIS value was higher than that at 24 hours after admission (P<0.05). Logistic regression analysis showed that ASCMP patients with increased S100β, Copeptin, and decreased BIS values had an increased risk of adverse events (P<0.05). The ROC curve showed that the area under the curve of the combined detection of BIS, S100β and Copeptin was 0.859, which had a great predictive value for the prognosis of ASCMP patients. Conclusion: BIS, S100β combined with Copeptin detection is of great value for early assessment of ASCMP disease and prognosis prediction.

Clinical characteristics of patients with acute pulmonary embolism in high altitude area of Yunnan province in China / 中华心血管病杂志

Objective: To analyze the clinical features of patients with acute pulmonary embolism (APE) living in high altitude area of Yunnan province. Methods: This was a cross-sectional retrospective study. APE patients, hospitalized in our hospital between January 2017 and December 2019, were included. The selected patients were divided into low-risk group, medium-risk group and high-risk group according to risk stratification. The clinical data of patients, including demographic data, the main symptoms, risk factors of APE, heart rate and systolic blood pressure and laboratory testing results (D-dimer, cardiac troponin I (cTNI), N terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography and electrocardiogram examination results, were obtained through the electronic medical record system. The clinical characteristics of selected patients were analyzed. Results: A total of 392 patients, aged (63.5±15.7) years, 224 males (57.14%), were included in this study and there were 59 low-risk, 304 medium-risk and 29 high-risk patients in this cohort. The main clinical manifestations were chest pain (157(40.05%)), dyspnea (107(27.30%)), hemoptysis (55(14.03%)), syncope as the first symptom (20(5.10%)), and only 6 cases (1.53%) presented with the typical "Virchow's triad". Most of the patients were accompanied by atypical chest tightness (223(56.89%)) and cough (208(53.06%)). The main risk factors were venous thrombosis of lower limbs (179(45.66%)), hypertension (138(35.20%)), surgery (63(16.07%)), and chronic obstructive pulmonary disease (COPD) (62(15.82%)). There were 57 cases (14.54%) of coronary heart disease, 57 cases (14.54%) of diabetes, 51 cases (13.01%) of cerebral infarction, 47 cases (12.00%) of advanced age, 15 cases (3.83%) of tumor, 7 cases (1.79%) of activity restriction, 6 cases (1.53%) of pregnancy and 4 cases (1.02%) of hormone use in this cohort. The proportion of lower extremity venous thrombosis was significantly higher in low-risk group than in medium-risk group (P<0.01), COPD was more common in high-risk and medium-risk groups than in low-risk group (P<0.01), hypertension was more common in high-risk group than in medium-and low-risk groups (P<0.01). The proportion of advanced age was significantly higher in medium-risk group than in low-risk group (P<0.01). There were no significant differences in RBC and hemoglobin level between low-, medium-and high-risk groups (P>0.05). The level of D-dimer was significantly higher in high-risk group than in medium-and low-risk groups (P<0.05). Levels of NT-proBNP and cTNI were significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). Increased proportion of cTNI and NT-proBNP was significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). There were 105 (26.79%) patients with pulmonary hypertension (PAH). The incidence of PAH was significantly higher in high-risk group than in low-risk group (P<0.01). There were 104 patients (26.53%) with right ventricular enlargement, and the incidence of right ventricular enlargement was significantly higher in high-risk group than in medium-and low-risk groups (P<0.01). Characteristic changes of electrocardiogram in patient with APE were T-wave inversion of limb leads (98(25.00%)), followed by SⅠQⅢTⅢ (83(21.17%)). Conclusions: The main clinical manifestations of APE in Yunnan high altitude area are chest pain and dyspnea, and syncope is the first symptom in some patients, but the typical "Virchow's triad" is rare. The most common risk factors are lower extremity venous thrombosis, hypertension, and COPD. Clinical symptoms, risk factors and laboratory examination results differ among patients with different risk stratification.

Diagnostic value of serum tumor markers CEA, CYFRA21-1, SCCAg, NSE and ProGRP for lung cancers of different pathological types / 南方医科大学学报

OBJECTIVE@#To evaluate the diagnostic value of the serum tumor markers carcinoembryonic antigen (CEA), cytokeratin-19-fragment (CYFRA21-1), squamous cell carcinoma associated antigen (SCCAg), neuron-specificenolase (NSE) and pro-gastrin-releasing peptide (ProGRP) for lung cancers of different pathological types.@*METHODS@#This study was conducted among patients with established diagnoses of lung adenocarcinoma (LADC, n=137), lung squamous cell carcinoma (LSCC, n=82), small cell lung carcinoma (SCLC, n=59), and benign chest disease (BCD, n=102). The serum tumor markers were detected for all the patients for comparison of the positivity rates and their serum levels. ROC curve was used for analysis of the diagnostic efficacy of these tumor markers either alone or in different combinations.@*RESULTS@#In patients with LADC, the positivity rate and serum level of CEA were significantly higher than those in the other groups (P < 0.05); the patients with LSCC had the highest positivity rate and serum level of SCCAg among the 4 groups (P < 0.05). The positivity rates and serum levels of ProGRP and NSE were significantly higher in SCLC group than in the other groups (P < 0.05). CYFRA21-1 showed the highest positivity rate and serum level in LADC group and LSCC group. With the patients with BCD as control, CEA showed a diagnostic sensitivity of 62.8% and a specificity of 93.1% for LADC, and the sensitivity and specificity of SCCAg for diagnosing LSCC were 64.6% and 91.2%, respectively. CYFRA21-1 had the highest diagnostic sensitivity for LADC and LSCC. The diagnostic sensitivity and specificity of ProGRP for SCLC were 83.1% and 98.0%, respectively. When combined, CYFRA21-1 and CEA showed a high sensitivity (78.8%) and specificity (86.3%) for diagnosing LADC with an AUC of 0.891; CYFRA21-1 and SCCAg had a high sensitivity (84.1%) and specificity (87.3%) for diagnosing LSCC with an AUC of 0.912. NSE combined with ProGRP was highly sensitive (88.1%) and specific (98.0%) for diagnosis of SCLC, with an AUC of 0.952. For lung cancers of different pathological types, the combination of all the 5 tumor markers showed no significant differences in the diagnostic power from a combined detection with any two of the markers (P>0.05).@*CONCLUSION@#CEA, CYFRA21-1, SCCAg, NSE and ProGRP are all related to the pathological type of lung cancers and can be used in different combinations as useful diagnostic indicators for lung cancers.

Predictive value of plasma TMAO combined with NT-proBNP on the prognosis and length of hospitalization of patients with ischemic heart failure / 中华心血管病杂志

Objective: To explore the value of the assessment of plasma trimethylamine N-oxide (TMAO) combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) on predicting the all-cause mortality, length of hospitalization, and hospital cost in ischemic heart failure (IHF) patients. Methods: This prospective cohort study included 189 patients (157 males, mean age (64.0±10.5) years) with a left ventricular ejection fraction<45% caused by coronary artery disease, who hospitalized in our department from March 2016 to December 2020. Baseline data, including demographics, comorbid conditions and laboratory examination, were analyzed. The cumulative rate of all-cause mortality was evaluated using the Kaplan-Meier method and compared between the groups according to the log-rank test. Relative risks were reported as hazard ratios (HR) and 95% confidence interval (95%CI) calculated using the Cox proportional-hazards analysis, with stepwise adjustment for covariables. Spearman correlation analysis was then performed to determine the relationship between TMAO combined with NT-proBNP and length of hospitalization and hospital cost. Results: There were 50 patients in the low TMAO+low NT-proBNP group, 89 patients in high TMAO or high NT-proBNP group, 50 patients in high TMAO+high NT-proBNP group. The mean follow-up period was 3.0 years. Death occurred in 70 patients (37.0%), 27 patients (54.0%) in high TMAO+high NT-proBNP group, 29 patients (32.6%) in high TMAO or high NT-proBNP group and 14 patients (28.0%) in low TMAO+low NT-proBNP group. TMAO, in combination with NT-proBNP, improved all-cause mortality prediction in IHF patients when stratified as none, one or both biomarker(s) elevation, with the highest risk of all-cause mortality in high TMAO+high NT-proBNP group (HR=3.62, 95%CI 1.89-6.96, P<0.001). ROC curve analysis further confirmed that TMAO combined with NT-proBNP strengthened the prediction performance on the risk of all-cause death (AUC=0.727(95%CI 0.640-0.813), sensitivity 55.0%, characteristic 83.1%). Spearman correlation analysis showed that IHF patients with high TMAO and high NT-proBNP were positively associated with longer duration of hospitalization (r=0.191,P=0.009), but not associated with higher hospital cost (r=0.030, P=0.686). Conclusions: TMAO combined with NT-proBNP are valuable prediction tool on risk stratification of patients with IHF, and those with two biomarkers elevation face the highest risk of mortality during follow-up period, and are associated with the longer hospital stay.

Impact of empagliflozin on peak oxygen uptake in HFmrEF patients: a randomized controlled trial / 中华心血管病杂志

Objective: To evaluate the impact of empagliflozin on peak oxygen uptake (VO2peak) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods: In this randomized controlled trial, consecutive HFmrEF patients admitted to the Department of Cardiology of China-Japan Friendship Hospital from September 2019 to October 2020 were screened, and randomly assigned to empagliflozin group (EG) or conventional group (CG) using a random number table. The enrolled patients were treated according to the guidelines, and patients in the empagliflozin group received additional empagliflozin (10 mg, once a day, orally) on top of the conventional treatment. The primary end points were VO2peak at 6 months after treatment, and the secondary end points included other parameters of cardiopulmonary exercise test (CPET), 6-minute walking distance, N-terminal B-type pro-natriuretic peptide (NT-proBNP) level, and Kansas City Cardiomyopathy Questionnaire (KCCQ) score. Results: A total of 112 patients were included (mean age 69 (57, 78) years, 84 male (75.0%)). There were 55 cases in CG group and 57 cases in EG group. There were no significant differences in baseline data including age, sex, body mass index, left ventricular ejection fraction, systolic blood pressure, heart rate, estimated glomerular filtration rate, glycosylated hemoglobin, hemoglobin, NT-proBNP, daily dose of tolasemi, combined medication, CPET parameters, the proportion of New York Heart Association heart function Ⅲ/Ⅳ, history of coronary heart disease, history of hypertension, history of diabetes (all P>0.05). At 6 months after treatment, VO2peak was significantly higher in EG group than in CG group(P=0.023). VE/VCO2 slope was significantly lower in EG group than in CG group(P=0.034). Oxygen uptake efficiency slope was significantly higher in EG group than in CG group(P=0.038). The level of NT-proBNP was significantly lower in EG group than in CG group(P=0.020). Six-minute walking distance was significantly higher in EG group than in CG group(P=0.037). KCCQ score was significantly higher in EG group than in CG group(P=0.048). Exercise oscillatory ventilation decreased in both groups (1 case in each group, P>0.05). Conclusion: Empagliflozin can significantly improve VO2peak in patients with HFmrEF.

Effect of Shenmai Injection on Long-Term Prognosis of Patients with Chronic Heart Failure: A Multicenter, Large Sample Capacity, Long-Term Follow-Up Retrospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Shenmai Injection (SMI) on the long-term prognosis of patients with chronic heart failure (CHF).@*METHODS@#The Hospital Information System was used to extract data of CHF patients, and the retrospective cohort study was conducted for analysis. In non-exposed group, standardized Western medicine treatment and Chinese patent medicine or decoction were applied without combination of SMI while in the exposed group, SMI were applied for more than 7 days. Evaluation indicators are followed with New York Heart Association functional classification (NYHA classification), left ventricular ejection fraction (LVEF), N-terminal brain natriuretic peptide precursor (NT-ProBNP), cardiogenic death and heart failure (HF) readmission. Statistical analysis includes Kaplan-Meier analysis and Cox regression which are used to explore the relationship between SMI and outcome events.@*RESULTS@#A total of 1,211 eligible CHF patients were involved and finally 1,047 patients were followed up successfully. After treatment, the cases of NYHA classification decline in the exposed and non-exposed groups accounted for 64.30% and 43.45%, respectively; the improvement values of LVEF were 8.89% and 7.91%, respectively; the improvement values of NT-ProBNP were 909 pg/mL and 735 pg/mL, respectively. After exposure on SMI, the rates of cardiogenic death and HF readmission reduced from 15.43% to 10.18% and 38.93% to 32.37%. According to Kaplan-Meier analysis, the log-rank P value of SMI and cardiogenic death was 0.014, while the counterpart of SMI and HF readmission was 0.025. Cox regression analysis indicated that for cardiogenic death, age, cardiomyopathy, diabetes, and NYHA classification were risk factors while β-blockers, aldosterone receptor antagonists, Chinese patent medicine/decoction and SMI were protective factors. Likewise, for HF readmission, age, cardiomyopathy, and NYHA classification were risk factors while SMI was a protective factor.@*CONCLUSION@#Combination with SMI on the standardized Western medicine treatment can effectively reduce cardiogenic mortality and readmission rate in CHF patients, and thereby improve the long-term prognosis.

Qishen Taohong Granule () as Adjuvant Therapy for Improving Cardiac Function and Quality of Life in Patients with Chronic Heart Failure: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To confirm the improvement of cardiac function and quality of life (QOL) in patients with chronic heart failure (CHF) via Chinese medicine (CM) Qishen Taohong Granule (, QTG).@*METHODS@#This study was a single-center, prospective, randomized, controlled clinical trial. Seventy-six patients from 27 to 84 years old diagnosed with CHF New York Heart Association (NYHA) class II or III in stage C were enrolled and randomly assigned at a 1:1 ratio to receive QTG or trimetazidine (TMZ), in addition to their standard medications for the treatment of CHF. The study period was 4 weeks. The primary outcomes included cardiac function evaluated by NYHA classification and left ventricular ejection fraction (LVEF), as well as QOL evaluated by CHF Integrated Chinese and Western Medicine Survival Scale (CHFQLS). The secondary outcomes included 6-min walking test (6MWT), CM syndrome score, symptom and sign scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP). All indices were measured at baseline and the end of the trial.@*RESULTS@#At the 4-week follow-up period, the effective rate according to NYHA classification in the QTG group was better than that in the TMZ group (74.29% vs. 54.29%, P<0.05). But there was no significant difference in post-treatment level of LVEF between the two groups (P>0.05). The CHFQLS scores improved by 13.82±6.04 vs. 7.49±2.28 in the QTG and TMZ groups, respectively (P<0.05). Subgroup analysis of the CHFQLS results showed that physiological function, role limitation and vitality were significantly higher in the QTG group than in the TMZ group (15.76±7.85 vs. 7.40±3.36, P<0.05; 16.00±8.35 vs. 10.53±4.64, P<0.05; 15.31±8.09 vs. 7.89±4.60, P<0.05). Compared with TMZ group, treatment with QTG also demonstrated superior performance with respect to 6MWT, CM syndrome, shortness of breath, fatigue, gasping, general edema and NT-proBNP level. No significant adverse reactions or adverse cardiac events occurred during treatment in either group.@*CONCLUSION@#In addition to conventional treatments, the use of QTG as an adjuvant therapy significantly improved cardiac function and QOL in patients with CHF class II or III in stage C. [Registration No. ChiCTR1900022036 (retrospectively registered)].

Valor Prognóstico dos Níveis Plasmáticos de NT-proBNP em Pacientes Hospitalizados com Mais de 80 Anos de Idade em um Hospital em Pequim, China / Prognostic Value of Plasma NT-proBNP levels in Hospitalized Patients Older than 80 Years of Age in a Hospital in Beijing, China

Resumo Fundamento Apesar das evidências crescentes de que o peptídeo natriurético N-terminal pró-cérebro (NT-proBNP) tem um valor prognóstico importante em adultos mais velhos, há dados limitados sobre seu valor preditivo prognóstico. Objetivos O objetivo deste estudo é avaliar o significado clínico do NT-proBNP em pacientes hospitalizados com mais de 80 anos de idade em Pequim, China. Métodos Este estudo prospectivo e observacional foi conduzido em 724 pacientes muito idosos em uma enfermaria geriátrica (idade ≥80 anos, variação, 80-100 anos, média, 86,6±3,0 anos). A análise de regressão linear multivariada foi utilizada para rastrear os fatores independentemente associados ao NT-proBNP, e o modelo de regressão de risco proporcional de Cox foi utilizado para rastrear as associações entre os níveis de NT-proBNP e os principais endpoints . Os principais endpoints avaliados foram mortes por todas as causas e ECAM. Valores de p <0,05 foram considerados estatisticamente significativos. Resultados As taxas de prevalência de doença cardíaca coronariana, hipertensão e diabetes mellitus foram 81,4%, 75,1% e 41,2%, respectivamente. O nível médio de NT-proBNP foi 770±818 pg/mL. Utilizando análises de regressão linear multivariada, foram encontradas correlações entre o NT-proBNP plasmático e índice de massa corporal, fibrilação atrial, taxa de filtração glomerular estimada, diâmetro do átrio esquerdo, fração de ejeção do ventrículo esquerdo, uso de betabloqueador, níveis de hemoglobina, albumina plasmática, triglicérides, creatinina sérica, e nitrogênio uréico no sangue. O risco de morte por todas as causas (HR, 1,63; IC 95%, 1,005-2,642; p = 0,04) e eventos cardiovasculares adversos maiores (ECAM; HR, 1,77; IC 95%, 1,289-3,531; p = 0,04) no grupo com o nível mais alto NT-proBNP foi significativamente maior do que no grupo com NT-proBNP mais baixo, de acordo com os modelos de regressão de Cox após o ajuste para vários fatores. Como esperado, os parâmetros da ecocardiografia ajustaram o valor prognóstico do NT-proBNP no modelo. Conclusões O NT-proBNP foi identificado como um preditor independente de morte por todas as causas e ECAM em pacientes hospitalizados com mais de 80 anos de idade.

Abstract Background Despite growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value in older adults, there is limited data on its prognostic predictive value. Objectives The aim of this study is to evaluate the clinical significance of NT-proBNP in hospitalized patients older than 80 years of age in Beijing, China. Methods This prospective, observational study was conducted in 724 very elderly patients in a geriatric ward (age ≥80 years, range, 80100 years, mean, 86.6 3.0 years). Multivariate linear regression analysis was used to screen for factors independently associated with NT-proBNP, and the Cox proportional hazard regression model was used to screen for relationships between NT-proBNP levels and major endpoints. The major endpoints assessed were all-cause death and MACEs. P values < 0.05 were considered statistically significant. Results The prevalence rates of coronary heart disease, hypertension, and diabetes mellitus were 81.4%, 75.1%, and 41.2%, respectively. The mean NT-proBNP level was 770 ± 818 pg/mL. Using multivariate linear regression analyses, correlations were found between plasma NT-proBNP and body mass index, atrial fibrillation, estimated glomerular filtration rate, left atrial diameter, left ventricular ejection fraction, use of betablocker, levels of hemoglobin, plasma albumin, triglycerides, serum creatinine, and blood urea nitrogen. The risk of all-cause death (HR, 1.63; 95% CI, 1.0052.642; P = 0.04) and major adverse cardiovascular events (MACE; HR, 1.77; 95% CI, 1.2893.531; P = 0.04) in the group with the highest NT-proBNP level was significantly higher than that in the group with the lowest level, according to Cox regression models after adjusting for multiple factors. As expected, echocardiography parameters adjusted the prognostic value of NT-proBNP in the model. Conclusions NT-proBNP was identified as an independent predictor of all-cause death and MACE in hospitalized patients older than 80 years of age.

Interação Letal entre Síndrome Hemofagocítica e Insuficiência Cardíaca Recentemente Desenvolvida / Mortal Interaction Between Hemophagocytic Syndrome and Newly Developed Heart Failure

Resumo Fundamento: A síndrome hemofagocítica (SHF) é uma síndrome hiperinflamatória debilitante. O status da insuficiência cardíaca (IC) com fração de ejeção preservada (ICFEP) está intimamente relacionado ao aumento da inflamação sistêmica e intramiocárdica. Objetivos: este estudo pretende determinar os preditores de mortalidade e os parâmetros de monitoramento confiáveis nos casos de SHF que desenvolveram a ICFEP durante seu curso clínico. Métodos: Trinta e nove pacientes, diagnosticados com SHF de acordo com os critérios diagnósticos do estudo HLH 2004 com Hscore ≥169, e com aspiração ou biópsia de medula óssea comprovada, foram recrutados retrospectivamente. Foram investigados retrospectivamente os fatores de risco tradicionais, como proteína C reativa sérica, níveis de albumina e ferritina com contagens de linfócitos e plaquetas, e fatores não tradicionais, como relação neutrófilolinfócito (NLR), relação linfócito-monócito (MLR), volume plaquetário médio (MPV) e pró-peptídeo natriurético cerebral N-terminal (NTproBNP). Analisou-se a relação entre os valores laboratoriais alterados ao longo do tempo entre si e com a mortalidade. O nível de significância geral foi de 5%. Resultados: Foi demonstrado que a alteração temporal dos níveis de índice cardiotorácico (ICT), NTproBNP sérico, ferritina, PCR e albumina foram detectados como sendo preditores de mortalidade (p<0,05, para todos) em análise univariada. As contagens de linfócitos e plaquetas com valores de NLR e MPV também foram significativos (p<0,05). A relação entre NT-proBNP e o aumento dos marcadores inflamatórios sistêmicos também foi considerada significativa. Além de fatores de risco tradicionais, os níveis de ferritina sérica, e os níveis de NLR, MLR e MPV foram considerados significativamente correlacionados entre si. Conclusão: Acompanhado de parâmetros de monitoramento confiáveis, o diagnóstico rápido e o tratamento antiinflamatório agressivo com controle rígido de volume podem salvar vidas de pacientes com SHF que sofrem de complicações por ICFEP. O monitoramento rígido da inflamação pode prever o resultado do paciente que sofre de ICFEP.

Abstract Background: Hemophagocytic syndrome (HPS) ia s devastating hyperinflammatory syndrome. Heart failure (HF) with preserved ejection fraction (HFpEF) status is closely correlated with increased inflammation, both systemic and intramyocardial. Objectives: This study sought to determine mortality predictors and reliable follow-up parameters in HPS that developed HFpEF during the clinical course. Method: Thirty-nine patients, diagnosed as HPS, according to HLH 2004 diagnostic criteria, with an HScore of ≥169 and proven bone marrow aspiration or biopsy, were recruited retrospectively. Both traditional, serum C-reactive protein, albumin and ferritin levels with lymphocyte, and platelet counts, as well as non-traditional risk factors, neutrophil-to-lymphocyte count (NLR), monocyte-to-lymphocyte count (MLR), mean platelet volume (MPV), and N-Terminal pro-brain natriuretic peptide (NTproBNP), were investigated retrospectively. The relationship between time-changed laboratory values both among themselves and with mortality. The overall significance level was set at 5%. Results: This study showed that temporal change of cardiothoracic ratio (CTR), serum NTproBNP, ferritin, CRP, and albumin levels were detected as mortality predictors (p<0.05, for all) in the univariate analysis. Lymphocyte and platelet counts with NLR and MPV values were also significant (p<0.05). The relationship between NT-proBNP and increased systemic inflammatory markers proved to be significant. In addition to traditional risk factors, serum ferritin levels, NLR, MLR, and MPV levels also proved to be significantly correlated with each other. Conclusion: Accompanied by reliable follow-up parameters, rapid diagnosis and aggressive anti-inflammatory treatment with tight volume control can be life-saving in HPS patients who suffer from HFpEF. Close monitoring of inflammation may predict the outcome of patients suffering from HFpEF.

Correlation between genotypes with metabolic markers and microstructure of bones in children with Gitelman syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation between the genotypes and metabolic markers and microstructure of bones in children with Gitelman syndrome (GS).@*METHODS@#For 15 children with GS and 10 healthy individuals, baseline data and bone metabolic markers including parathyroid hormone, alkaline phosphatase, osteocalcin, N-terminal propeptide of type I procollagen, beta isomer of the C-terminal telopeptide of type I collagen and 25-hydroxyvitamin D, high-resolution peripheral quantitative computed tomography indicators (volumetric bone mineral density, bone microstructure indicators) were collected. Genetic testing was carried out to determine their genotypes.@*RESULTS@#The volumetric bone mineral density, bone geometry and bone microstructure parameters of the GS group were better than those of the healthy controls (P<0.05). Variants of the SLC12A3 gene were identified in 9 of the 15 patients but none of the 10 healthy controls.@*CONCLUSION@#The phenotype of GS children is influenced by the interaction of genetic variants, though the phenotype associated with high frequency mutations showed no specificity. There is also a correlation between their genotype and the bone microstructure.

Development and evaluation of a chemiluminescence immunoassay for type Ⅰ procollagen N-terminal peptide / 生物工程学报

To develop a magnetic nanoparticle chemiluminescence immunoassay (CLIA) for the determination of type Ⅰ procollagen N-terminal peptide (PINP) in human serum, we expressed a recombinant PINP-α1 protein in Corynebacterium glutamicum and used it as an immunogen to immunize BALB/c mice. We obtained three hybridoma cell lines that stably secret antibody against PINP-α1 protein. After further pairing and screening, we chose a monoclonal antibody 8C12 coupled with biotin as the capture antibody, and a monoclonal antibody 1F11 labeled horseradish peroxidase as the detection antibody. The antibodies combined with the serum samples, forming a sandwich complex which was used to detect the concentration of PINP in serum. After optimizing the conditions, we determined that the best working concentration of the capture antibody and the detection antibody were 3 μg/mL, and the incubation time was 30 minutes. The quantitative assay had a detection range of 5-1 100 ng/mL, with recovery rates between 93%-107% and the minimum detection limit of 1.22 ng/mL achieved. The intra-and inter-assay precisions were lower than 10%. The correlation coefficient of PINP results between this CLIA method and the Roche electrochemiluminescence immunoassay system was 0.906 2. Therefore, this CLIA method is specific and can be used to quantitatively detect the content of PINP in serum, which has the potential to become an auxiliary approach for bone disease examination.

PTK2B affects the levels of Aβ in blood and brain and behavioral functions via targeting LRP-1 transporter in Aβ-induced cognitive dysfunction mice / 生理学报

The aim of the present study was to explore the correlation between ptk2b/PTK2B (protein tyrosine kinase 2 beta, a ptk2b-encoded protein) and the level of low density lipoprotein receptor-related protein-1 (LRP-1), as well as to uncover the relationship between the changes in beta amyloid protein (Aβ) levels in blood and brain and the expression of ptk2b in Aβ-induced cognitive dysfunction mice. A total of 64 3-month-old C57BL/6J mice were divided randomly into the experimental group and control group. All mice underwent the intracerebroventricular (i.c.v.) intubation. Mice in the experimental group received the i.c.v. infusion of oligomeric Aβ

Donor-specific antibodies, glomerulitis, and human leukocyte antigen B eplet mismatch are risk factors for peritubular capillary C4d deposition in renal allografts / 中华医学杂志(英文版)

BACKGROUND@#The complement system plays an important role in the immune response to transplantation, and the diagnostic significance of peritubular capillary (PTC) C4d deposition (C4d+) in grafts is controversial. The study aimed to fully investigate the risk factors for PTC C4d+ and analyze its significance in biopsy pathology of kidney transplantation.@*METHODS@#This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody (DSA) testing from January 2017 to December 2019 in a single center. The effects of recipient pathological indicators, eplet mismatch (MM), and DSAs on PTC C4d+ were examined using univariate and multivariate logistic regression analyses.@*RESULTS@#In total, 35/124 (28%) were PTC C4d+, including 21 with antibody-mediated rejection (AMR), eight with renal tubular injury, three with T cell-mediated rejection, one with glomerular disease, and two others. Univariate analysis revealed that DSAs (P < 0.001), glomerulitis (P < 0.001), peritubular capillaritis (P < 0.001), and human leukocyte antigen (HLA) B eplet MM (P = 0.010) were the influencing factors of PTC C4d+. According to multivariate analysis, DSAs (odds ratio [OR]: 9.608, 95% confidence interval [CI]: 2.742-33.668, P < 0.001), glomerulitis (OR: 3.581, 95%CI: 1.246-10.289, P = 0.018), and HLA B eplet MM (OR: 1.166, 95%CI: 1.005-1.353, P = 0.042) were the independent risk factors for PTC C4d+. In receiver operating characteristic curve analysis, the area under the curve was increased to 0.831 for predicting PTC C4d+ when considering glomerulitis, DSAs, and HLA B eplet MM. The proportions of HLA I DSAs and PTC C4d+ in active antibody-mediated rejection were 12/17 and 15/17, respectively; the proportions of HLA class II DSAs and PTC C4d+ in chronic AMR were 8/12 and 7/12, respectively. Furthermore, the higher the PTC C4d+ score was, the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy.@*CONCLUSIONS@#PTC C4d+ was mainly observed in AMR cases. DSAs, glomerulitis, and HLA B eplet MM are the independent risk factors for PTC C4d+.

Abdominal acupoint thread embedding therapy based on "brain-intestinal connection" for mild-to-moderate Alzheimer's disease and its effects on serum levels of APP and Aβ / 中国针灸

OBJECTIVE@#To compare the clinical efficacy of abdominal acupoint thread embedding therapy based on "brain-intestinal connection" combined with donepezil hydrochloride tablets and oral donepezil hydrochloride tablets alone for mild-to-moderate Alzheimer's disease (AD) and observe its effects on amyloid precursor protein (APP) and β-amyloid protein@*METHODS@#Sixty patients with AD were randomly divided into an observation group (30 cases, 3 cases dropped off) and a control group (30 cases, 3 cases dropped off). The patients in the control group were treated with donepezil hydrochloride tablets (5 mg per day); based on the treatment in the control group, the patients in the observation group were treated with abdominal acupoint thread embedding therapy at Zhongwan (CV 12), Xiawan (CV 10), Huaroumen (ST 24), Wailing (ST 26), Daheng (SP 15), etc., once every 10 days. Both groups were treated for 2 months. The mini-mental state examination (MMSE), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), activity of daily living scale (ADL), neuropsychiatric inventory questionnaire (NPI) as well as the serum levels of APP and Aβ@*RESULTS@#After treatment, the MMSE scores in the two groups were higher than those before treatment (@*CONCLUSION@#The abdominal acupoint thread embedding therapy based on the theory of "brain-intestinal connection" combined with donepezil hydrochloride tablets can improve cognitive function, self-care ability of daily life and mental behavior, and reduce the serum levels of APP and Aβ

Urinary N-terminal pro-B-type natriuretic peptide as a biomarker for cardiovascular events in a general Japanese population: the Hisayama Study

BACKGROUND@#Epidemiological evidence has shown that serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, a diagnostic biomarker for heart failure, are positively associated with cardiovascular risk. Since NT-proBNP in serum is excreted in urine, it is hypothesized that urinary NT-proBNP concentrations are correlated with serum concentrations and linked with cardiovascular risk in the general population.@*METHODS@#A total of 3060 community-dwelling residents aged ≥ 40 years without history of cardiovascular disease (CVD) were followed up for a median of 8.3 years (2007-2015). Serum and urinary concentrations of NT-proBNP at baseline were compared. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between NT-proBNP concentrations and the risk of developing CVD were computed using the Cox proportional hazards model.@*RESULTS@#The median values (interquartile ranges) of serum and urinary NT-proBNP concentrations at baseline were 56 (32-104) pg/mL and 20 (18-25) pg/mL, respectively. There was a strong quadratic correlation between the serum and urinary concentrations of NT-proBNP (coefficient of determination [R@*CONCLUSIONS@#The present study demonstrated that urinary NT-proBNP concentrations were well-correlated with serum concentrations and were positively associated with cardiovascular risk. Given that urine sampling is noninvasive and does not require specially trained personnel, urinary NT-proBNP concentrations have the potential to be an easy and useful biomarker for detecting people at higher cardiovascular risk.

Change of serum levels of pentraxin-3 and syndecan-4 in children with chronic heart failure / 中国当代儿科杂志

OBJECTIVE@#To study the change and significance of serum pentraxin-3 (PTX-3) and syndecan-4 in children with chronic heart failure (CHF).@*METHODS@#A total of 40 children with CHF who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University were enrolled as the heart failure group, and 30 children who underwent physical examination in the outpatient service during the same period of time were enrolled as the control group. The serum levels of PTX-3, syndecan-4, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were compared between the two groups.@*RESULTS@#The children with CHF had significant reductions in the serum levels of PTX-3, syndecan-4, and NT-proBNP after treatment. The levels of these markers in children with CHF were significantly higher than the control group before and after treatment (@*CONCLUSIONS@#Serum PTX-3 and syndecan-4 may be involved in the development and progression of ventricular remodeling in children with CHF and may be used as markers for the diagnosis, cardiac function grading, and treatment outcome evaluation of children with heart failure.

Amyloid and tau positive mild cognitive impairment: clinical and biomarker characteristics of dementia progression / 中华医学杂志(英文版)

BACKGROUND@#According to the amyloid, tau, neurodegeneration research framework classification, amyloid and tau positive (A+T+) mild cognitive impairment (MCI) individuals are defined as prodromal Alzheimer disease. This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI (pMCI) and those who remained stable MCI (sMCI), and to identify relevant baseline clinical biomarker and features that could be used to predict progression to dementia within 2 years.@*METHODS@#We stratified 197 A+T+MCI individuals into pMCI (n = 64) and sMCI (n = 133) over 2 years. Demographics and cognitive assessment scores, cerebrospinal fluid (CSF), and neuroimaging biomarkers (18F-florbetapir positron emission tomography mean standardized uptake value ratios [SUVR] and structural magnetic resonance imaging [MRI]) were compared between pMCI and sMCI at baseline, 12- and 24-month follow-up. Logistic regression models then were used to evaluate clinical baseline and biomarker features that predicted dementia progression in A+T+MCI.@*RESULTS@#pMCI individuals had higher mean 18F-florbetapir SUVR, CSF total-tau (t-tau), and p-tau181P than those in sMCI individuals. pMCI individuals performed poorer in cognitive assessments, both global and domain specific (memory, executive, language, attention, and visuospatial skills) than sMCI. At baseline, there were significant differences in regions of interest of structural MRI between the two groups, including bilateral amygdala, hippocampus and entorhinal, bilateral inferior lateral ventricle, left superior and middle temporal, left posterior and caudal anterior cingulate (P < 0.05). Baseline CSF t-tau levels and cognitive scores of Montreal cognitive assessment, functional assessment questionnaire, and everyday cognition by the patient's study partner language domain could predict progression to dementia in A+T+MCI within 2 years.@*CONCLUSIONS@#In future clinical trials, specific CSF and cognitive measures that predict dementia progression in A+T+MCI might be useful risk factors for assessing the risk of dementia progression.

Long-term outcomes and independent predictors of mortality in patients presenting to emergency departments with acute heart failure in Beijing: a multicenter cohort study with a 5-year follow-up / 中华医学杂志(英文版)

BACKGROUND@#Acute heart failure (AHF) is the most common disease in emergency departments (EDs). However, clinical data exploring the outcomes of patients presenting AHF in EDs are limited, especially the long-term outcomes. The purposes of this study were to describe the long-term outcomes of patients with AHF in the EDs and further analyze their prognostic factors.@*METHODS@#This prospective, multicenter, cohort study consecutively enrolled 3335 patients with AHF who were admitted to EDs of 14 hospitals from Beijing between January 1, 2011 and September 23, 2012. Kaplan-Meier and Cox regression analysis were adopted to evaluate 5-year outcomes and associated predictors.@*RESULTS@#The 5-year mortality and cardiovascular death rates were 55.4% and 49.6%, respectively. The median overall survival was 34 months. Independent predictors of 5-year mortality were patient age (hazard ratio [HR]: 1.027, 95 confidence interval [CI]: 1.023-1.030), body mass index (BMI) (HR: 0.971, 95% CI: 0.958-0.983), fatigue (HR: 1.127, 95% CI: 1.009-1.258), ascites (HR: 1.190, 95% CI: 1.057-1.340), hepatic jugular reflux (HR: 1.339, 95% CI: 1.140-1.572), New York Heart Association (NYHA) class III to IV (HR: 1.511, 95% CI: 1.291-1.769), heart rate (HR: 1.003, 95% CI: 1.001-1.005), diastolic blood pressure (DBP) (HR: 0.996, 95% CI: 0.993-0.999), blood urea nitrogen (BUN) (HR: 1.014, 95% CI: 1.008-1.020), B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in the third (HR: 1.426, 95% CI: 1.220-1.668) or fourth quartile (HR: 1.437, 95% CI: 1.223-1.690), serum sodium (HR: 0.980, 95% CI: 0.972-0.988), serum albumin (HR: 0.981, 95% CI: 0.971-0.992), ischemic heart diseases (HR: 1.195, 95% CI: 1.073-1.331), primary cardiomyopathy (HR: 1.382, 95% CI: 1.183-1.614), diabetes (HR: 1.118, 95% CI: 1.010-1.237), stroke (HR: 1.252, 95% CI: 1.121-1.397), and the use of diuretics (HR: 0.714, 95% CI: 0.626-0.814), β-blockers (HR: 0.673, 95% CI: 0.588-0.769), angiotensin-converting enzyme inhibitors (ACEIs) (HR: 0.714, 95% CI: 0.604-0.845), angiotensin-II receptor blockers (ARBs) (HR: 0.790, 95% CI: 0.646-0.965), spironolactone (HR: 0.814, 95% CI: 0.663-0.999), calcium antagonists (HR: 0.624, 95% CI: 0.531-0.733), nitrates (HR: 0.715, 95% CI: 0.631-0.811), and digoxin (HR: 0.579, 95% CI: 0.465-0.721).@*CONCLUSIONS@#The results of our study demonstrate poor 5-year outcomes of patients presenting to EDs with AHF. Age, BMI, fatigue, ascites, hepatic jugular reflux, NYHA class III to IV, heart rate, DBP, BUN, BNP/NT-proBNP level in the third or fourth quartile, serum sodium, serum albumin, ischemic heart diseases, primary cardiomyopathy, diabetes, stroke, and the use of diuretics, β-blockers, ACEIs, ARBs, spironolactone, calcium antagonists, nitrates, and digoxin were independently associated with 5-year all-cause mortality.

Função Diastólica e Biomarcadores de Participantes de Caminhada de Longa Distância / Diastolic Function and Biomarkers of Long-Distance Walking Participants

Resumo Fundamento: Os efeitos da caminhada de longa distância sobre o sistema cardiovascular são pouco estudados. Objetivos: O objetivo geral deste estudo foi verificar esses efeitos sobre o comportamento da função diastólica e dos biomarcadores cardíacos CK-MB (massa), troponina T e NT-proBNP em atletas amadores. Método: Este estudo longitudinal realizado em 2015 avaliou os participantes nas 5 etapas seguintes: A0 (basal) antes de iniciar o percurso, e as demais, A1, A2, A3 e A4 ao final de cada dia, totalizando 244,7 km. Em todas as etapas foram dosados os biomarcadores NT-proBNP, CK-MB (massa) e troponina T. Realizou-se ecocardiograma para análise das ondas E, A e E'. Adotado p < 0,05 como significativo. Resultados: Foram avaliados 25 participantes com média de idade de 46 ± 10,5 anos e índice de massa corporal de 20,2 ± 2,3 kg/m2. Encontrou-se aumentos dos valores de NT-proBNP de A0 para A1, A2, A3 e A4 (p < 0,001), CK-MB (massa) de A0 para A2 (p < 0,001) e da onda E' de A0 para A1, A2, A3 e A4 (p < 0,001). Foram identificadas correlações entre os seguintes: CK-MB (massa) e troponina T (A1: r = 0,524, p = 0,010; A4: r = 0,413, p = 0,044); CK-MB (massa) e NT-proBNP (A4: r = 0,539, p = 0,006); e E/A e E' (A0: r = 0,603, p < 0,001; A1: r = 0,639, p < 0,001; A4: r = 0,593, p = 0,002); e correlação negativa entre CK-MB (massa) com E/A (A1: r = −0,428, p = 0,041). Conclusão: Os efeitos da atividade física intensa, prolongada e intercalada foram verificados a partir das variações significativas no comportamento da CK-MB (massa), NT-proBNP e E'. Apesar das alterações encontradas, não houve critérios sugestivos de dano ao miocárdio.

Abstract Background: The effects of long-distance walking on the cardiovascular system have been little studied. Objectives: The general objective of this study was to verify these effects on the behavior of diastolic function and the cardiac biomarkers CK-MB (mass), troponin T, and NT-proBNP, in amateur athletes. Method: This longitudinal study, conducted in 2015, evaluated participants during the following 5 stages: E0 (baseline) before starting the trajectory and the others, E1, E2, E3, and E4, at the end of each day, totaling 244.7 km. At all stages, the biomarkers NT-proBNP, CK-MB (mass), and troponin T were measured. Echocardiogram was performed to analyze the E, A and E' waves. P < 0.05 was adopted as significant. Results: The study evaluated 25 participants, with an average age of 46 ± 10.5 years and body mass index of 20.2 ± 2.3 kg/m2. Increased values were found for NT-proBNP from E0 to E1, E2, E3, and E4 (p < 0.001), CK-MB (mass) from E0 to E2 (p < 0.001), and E' wave from E0 to E1, E2, E3, and E4 (p < 0.001). Positive correlations were identified between the following: CK-MB (mass) and troponin T (E1: r = 0.524, p = 0.010; E4: r = 0.413, p = 0.044); CK-MB (mass) and NT-proBNP (E4: r = 0.539, p = 0.006); and E/A and E' (E0: r = 0.603, p < 0.001; E1: r = 0.639, p < 0.001; E4: r = 0.593, p = 0.002). A negative correlation was found between CK-MB (mass) and E/A (E1: r = −0.428, p = 0.041). Conclusion: The effects of intense, prolonged, and interspersed physical activity were verified based on significant variations in the behavior of CK-MB (mass), NT-proBNP, and the E' wave. Notwithstanding the alterations found, there were no criteria suggestive of myocardial damage

Melatonin has a stimulatory effect on osteoblasts by upregulating COL-I and OPN expression/secretion / Melatonina tem efeito estimulador em osteoblastos, pela regulação positiva da expressão/secreção de COL-I e OPN

ABSTRACT Melatonin (MLT) is a potential signaling molecule in the homeostasis of bone metabolism and may be an important mediator of bone formation and stimulation. The aim of this in vitro study was to evaluate the effect of MLT on the viability, mRNA/protein expression and mineralization of pre-osteoblastic cells. The concentrations 5, 2.5, 1, 0.1 and 0.01 mM MLT were tested on pre-osteoblastic cells (MC3T3) compared to control (no MLT), evaluating proliferation and cell viability (C50), gene expression (RT-PCR) and secretion (ELISA) of COL-I and OPN at 24h, 48h and 72h, and the formation of mineral nodules (alizarin red and fast red) after 10 days of treatment. MLT at 5 and 2.5 mM proved to be cytotoxic (C50), so only 0.01, 0.1 and 1 mM were used for the subsequent analyses. OPN mRNA expression increased with MLT at 0.1 mM - 1 mM, which was followed by increased secretion of OPN both at 24h and 72h compared to the remaining groups (p <0.05). COL-I mRNA and COL-1 secretion followed the same pattern as OPN at 0.1 mM MLT at 72h of treatment (p <0.05). Regarding mineralization, all MLT doses (except 1mM) caused an increase (p <0.05) in the formation of mineral nodules compared to the control. Melatonin at 0.01mM - 1mM had a stimulatory effect on osteoblasts by upregulating COL-I and OPN expression/ secretion and mineralization, thereby fostering osteogenesis.

RESUMO A melatonina (MLT) é uma molécula potencial de sinalização na homeostase do metabolismo ósseo e pode ser um importante mediador da formação e estimulação óssea. O objetivo deste estudo in vitro foi avaliar o efeito da MLT na viabilidade, na expressão do mRNA da proteína e mineralização de células préosteoblásticas. As concentrações de MLT 5, 2,5, 1, 0,1 e 0,01 mM foram testadas em células pré-osteoblásticas da linhagem MC3T3 em comparação ao controle (sem MLT), avaliando a proliferação e a viabilidade celular (C50), expressão gênica (rtPCR) e secreção (Elisa) de Colágeno tipo 1 (COL-I) e osteopontina (OPN) às 24, 48 e 72 horas, além da formação de nódulos minerais por meio do teste vermelho de Alizarina fast red após 10 dias de tratamento. MLT a 5 e 2,5 mM provou ser tóxico (C50). Portanto, as concentrações de 0,01, 0,1 e 1 mM foram utilizadas para as análises subsequentes. A expressão do mRNA da OPN aumentou com MLT a 0,1 mM-1mM, seguida pela secreção aumentada de OPN às 24 e 72 horas em comparação aos demais grupos (p<0,05). O mRNA de COL-I e a secreção de COL-I seguiram o mesmo padrão do OPN a 0,1 mM de MLT em 72 horas de tratamento (p<0,05). Em relação à mineralização, todas as doses de MLT (exceto 1mM) causaram aumento (p<0,05) na formação de nódulos minerais em comparação ao controle. A MLT na concentração entre 0,01mM a 1 mM teve um efeito estimulador sobre os osteoblastos, ao regular positivamente a expressão e secreção de COL-I e OPN, além da mineralização, favorecendo a osteogênese.