Soluble ST2 for predicting heart failure, atrial fibrillation and death in patients with coronary heart disease with or without renal insufficiency.

Background: This study aimed to investigate the relationship between baseline soluble suppression of tumorigenesis-2 (sST2) concentration and the outcomes of heart failure (HF), atrial fibrillation (AF) or death in patients with coronary heart disease (CHD) with or without renal insufficiency (RI). Methods: Between March 2011 and December 2015, 3454 patients with CHD from the Chinese PLA General Hospital were enrolled in this cohort study. The patients were followed up until October 2021. AF, HF, and death events were recorded. Associations between baseline sST2 concentrations and clinical outcomes were assessed using Kaplan-Meier (K-M) curves, and Cox regression and generalised additive models. Subgroup analysis were carried out between RI and non-RI groups. Results: Among the patients with CHD (61.5 ± 11.8 years; 78.6 % men), 415 (12.02 %) had RI. During a median follow-up of 8.37 years, HF and AF were reported in 216 (6.25 %) and 174 (5.04 %) patients, respectively, and 297 (8.60 %) died. The K-M curves indicated that patients in the higher quartiles of sST2 concentrations were correlated with a poor survival rate of HF, AF, or death (all Ps < 0.001). Generalised additive model (GAM) demonstrated a nonlinear positive association between sST2 concentration and the risk of HF, AF, and death in CHD patients. The cut-off value of sST2 for predicting HF, AF and death were 32.1, 25.4 and 28.6 ng/mL, respectively. CHD patients with sST2 higher than the cut-off value had higher risks of HF (HR: 3.02, 95%CI: 2.24-4.05), AF (HR: 2.86; 95%CI: 2.10-3.90), and death (HR:2.11, 95%CI: 1.67-2.67). Furthermore, in patients with RI (12.02 %, n = 415), the prognostic value of sST2 over the cut-off value for HF and death remained unchanged (HR: 3.21 and 2.35; P < 0.05). In patients with CHD with or without RI, sST2 improved the area under the curve (AUC) of traditional risk models for predicting clinical endpoint events. Conclusions: The biomarker sST2 may be useful for predicting HF, AF, and death in patients with CHD. The predicted value was not affected by renal function.

A Transvaginal Ultrasound-Based Deep Learning Model for the Noninvasive Diagnosis of Myometrial Invasion in Patients with Endometrial Cancer: Comparison with Radiologists.

RATIONALE AND OBJECTIVES: This study aimed to determine the feasibility of using the deep learning (DL) method to determine the degree (whether myometrial invasion [MI] >50%) of MI in patients with endometrial cancer (EC) based on ultrasound (US) images. MATERIALS AND METHODS: From September 2017 to April 2023, 1289 US images of 604 patients with EC who underwent surgical resection at center 1, center 2 or center 3 were obtained and divided into a training set and an internal validation set. Ninety-five patients from center 4 and center 5 were randomly selected as the external testing set according to the same criteria as those for the primary cohort. This study evaluated three DL models trained on the training set and tested them on the validation and testing sets. The models' performance was analyzed based on accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), and the performance of the models was subsequently compared with that of 15 radiologists. RESULTS: In the final clinical diagnosis of MI in patients with EC, EfficientNet-B6 showed the best performance in the testing set in terms of area under the curve (AUC) [0.814, 95% CI (0.746-0.882]; accuracy [0.802, 95% CI (0.733-0.855]; sensitivity [0.623]; specificity [0.879]; positive likelihood ratio (PLR) [6.750]; and negative likelihood ratio (NLR) [0.389]. The diagnostic efficacy of EfficientNet-B6 was significantly better than that of the 15 radiologists, with an average diagnostic accuracy of 0.681, average AUC of 0.678, AUC of the best performance of 0.739, accuracy of 0.716, sensitivity of 0.806, specificity 0.672, PLR2.457, and NLR 0.289. CONCLUSION: Based on the preoperative US images of patients with EC, the DL model can accurately determine the degree of endometrial MI; the performance of this model is significantly better than that of radiologists, and it can effectively assist in clinical treatment decisions.

The prognostic significance of human ovarian aging-related signature in breast cancer after surgery: A multicohort study.

Background: Recent studies have shown that ovarian aging is strongly associated with the risk of breast cancer, however, its prognostic impact on breast cancer is not yet fully understood. In this study, we performed a multicohort genetic analysis to explore its prognostic value and biological features in breast cancer. Methods: The gene expression and clinicopathological data of 3366 patients from the The Cancer Genome Atlas (TCGA) cohort, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort and the GSE86166 cohort were analyzed. A total of 290 ovarian aging-related genes (OARGs) were included in the establishment of the prognostic model. Furthermore, functional mechanisms analysis, drug sensitivity, and immune cell infiltration were investigated using bioinformatic methods. Results: An eight OARG-based signature was established and validated using independent cohorts. Two risk subgroups of patients with distinct survival outcomes were identified by the OARG-based signature. A nomogram with good predictive performance was developed by integrating the OARG risk score with clinicopathological factors. Moreover, the OARG-based signature was correlated with DNA damage repair, immune cell signaling pathways, and immunomodulatory functions. The patients in the low-risk subgroup were found to be sensitive to traditional chemotherapeutic, endocrine, and targeted agents (doxorubicin, tamoxifen, lapatinib, etc.) and some novel targeted drugs (sunitinib, pazopanib, etc.). Moreover, patients in the low-risk subgroup may be more susceptible to immune escape and therefore respond less effectively to immunotherapy. Conclusions: In this study, we proposed a comprehensive analytical method for breast cancer assessment based on OARG expression patterns, which could precisely predict clinical outcomes and drug sensitivity of breast cancer patients.

Hypofractionated versus conventional intensity-modulated radiation irradiation (HARVEST-adjuvant): study protocol for a randomised non-inferior multicentre phase III trial.

INTRODUCTION: Short course regimen has become the major trend in the field of adjuvant radiotherapy for patients with breast cancer. Hypofractionated radiotherapy (HF-RT) regimen of 40-42.5 Gy in 15-16 fractions has been established as a preferred option for whole breast irradiation. However, few evidences of hypofractionated regional nodal irradiation (RNI), especially involving internal mammary nodes (IMNs), could be available during the era of intensity-modulated radiation therapy (IMRT). Against this background, we design this trial to explore the hypothesis that HF-RT regimen involving RNI (including infraclavicular, supraclavicular nodes and IMNs) will be non-inferior to a standard schedule by using IMRT technique. METHODS AND ANALYSIS: This is an open-label randomised, non-inferior, multicentre phase III trial. Patients with breast cancer with an indication for RNI after breast conserving surgery or mastectomy are randomised at a ratio of 1:1 into the following two groups: hypofractionated regimen of 2.67 Gy for 16 fractions or conventional regimen of 2 Gy for 25 fractions. The dose was prescribed to ipsilateral chest wall or whole breast and RNI (including infraclavicular, supraclavicular nodes and IMNs, lower axilla if indicated). The trial plans to enrol a total of 801 patients and all patients will be treated using IMRT technique. The primary endpoint is 5-year locoregional recurrence. The secondary endpoints include 5-year distant metastasis free survival, invasive recurrence-free survival, overall survival, accumulative acute radiation-induced toxicity and accumulative late radiation-induced toxicity, cosmetic outcomes and quality of life. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine (version 2018-95-3) and approvals from ethical committee of each participating centre have also been obtained. Research findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03829553.

Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care.

One of the most effective treatments for diabetes is to design a glucose-regulated insulin (INS) delivery system that could adjust the INS release time and rate to reduce diabetes-related complications. Here, mixed multiple layer-by-layer (mmLbL)-INS microspheres were developed for glucose-mediated INS release and an enhanced hypoglycemic effect for diabetes care. To achieve ultrafast glucose-activated INS release, glucose oxidase (GOx) was assembled with a positively charged polymer and modified on INS LbL. The mmLbL-INS microspheres were constructed with one, two, and four layers of the polyelectrolyte LbL assembly at a ratio of 1:1:1. Under hyperglycemia, GOx converts a change in the hyperglycemic environment to a pH stimulus, thus providing sufficient hydrogen ion. The accumulated hydrogen ion starts LbL charge shifting, and anionic polymers are converted to cationic polymers through hydrolytic cleavage of amine-functionalized side chains. The results of in vitro INS release suggested that glucose can modulate the mmLbL-INS microspheres in a pulsatile profile. In vivo studies validated that this formulation enhanced the hypoglycemic effect in STZ-induced diabetic rats within 2 h of subcutaneous administration and facilitated stabilization of blood glucose levels for up to 2 days. This glucose-activatable LbL microsphere system could serve as a powerful tool for constructing a precisely controlled release system.

Tandem Electro-Oxidative C-C and C-N Coupling and Aromatization for the Construction of Pyrazine-Fused Bis-aza[7]helicene.

Repeated tandem electro-oxidative C-C and C-N coupling and aromatization were employed for the efficient construction of aza[7]helicene (BA7) as a key intermediate and the targeted pyrazine-fused bis-aza[7]helicene (PBBA7) derivatives in 90.0-93.2% isolated yields under a controlled potential. The electrosynthetic protocol showed high selectivity and enabled rapid access to functionalized organic conjugated materials from readily available polycyclic aromatic amines. A synthetic mechanistic study along with an investigation of the photoelectrical properties and application of PBBA7-C16 as a potential hole-transporting material for perovskite solar cells were performed.

Does the primary tumor site in stage I extranodal natural killer/T-cell lymphoma matter?

The purpose of this study was to investigate whether the primary tumor site in stage I extranodal natural killer/T-cell lymphoma (ENKTCL) had a prognostic value. Between January 2009 and December 2015, 152 stage I ENKTCL patients with primary disease in the nasal cavity and Waldeyer's ring were enrolled for this retrospective study. All patients received extended field intensity-modulated radiotherapy alone without prophylactic cervical node irradiation at a total dose of 50 Gy. In this study, there were 122 patients whose primary tumors were localized in the nasal cavity (NC group), and no adjacent structures were involved. A total of 18 patients had a primary disease involving the nasal cavity and Waldeyer's ring (NC-WR group), and the remaining 12 patients had primary tumors confined to Waldeyer's ring (WR group). We found that there was no significant difference in cervical lymph node failure rates among the NC, NC-WR, and WR groups. In terms of the 5-year overall survival (OS) rates, there was a significant difference among the NC, NC-WR, and WR groups (p=0.004), with the WR group having the worst OS. Multivariate analyses showed that the primary site (p=0.011) and ECOG (Eastern Cooperative Oncology Group) score (p=0.013) were independent prognostic factors for OS. In summary, patients with stage I ENKTCL had a good local control rate with radiotherapy alone and without prophylactic cervical node irradiation (PCNI), regardless of the site of the primary tumor. So, we think PCNI for stage I ENKTCL patients is not necessary. Patients with a primary tumor site located in Waldeyer's ring had the worst prognosis. And combined treatment with radiotherapy and chemotherapy should be considered in patients with primary tumors located outside the nasal cavity.

Effects of cat ownership on the gut microbiota of owners.

Pet ownership is an essential environmental exposure that might influence the health of the owner. This study's primary objectives were to explore the effects of cat ownership on the gut microbial diversity and composition of owners. Raw data from the American Gut Project were obtained from the SRA database. A total of 214 Caucasian individuals (111 female) with cats and 214 individuals (111 female) without cats were used in the following analysis. OTU number showed significant alteration in the Cat group and Female_cat group, compared with that of the no cat (NC) group and Female_ NC group, respectively. Compared with the NC group, the microbial phylum Proteobacteria was significantly decreased in the Cat group. The microbial families Alcaligenaceae and Pasteurellaceae were significantly reduced, while Enterobacteriaceae and Pseudomonadaceae were significantly increased in the Cat group. Fifty metabolic pathways were predicted to be significantly changed in the Cat group. Twenty-one and 13 metabolic pathways were predicted to be significantly changed in the female_cat and male_cat groups, respectively. Moreover, the microbial phylum Cyanobacteria was significantly decreased, while the families Alcaligenaceae, Pseudomonadaceae and Enterobacteriaceae were significantly changed in the normal weight cat group. In addition, 41 and 7 metabolic pathways were predicted to be significantly changed in the normal-weight cat and overweight cat groups, respectively. Therefore, this study demonstrated that cat ownership could influence owners' gut microbiota composition and function, especially in the female group and normal-weight group.

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

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.

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.

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.

Metabolic profiling reveals alterations in the erythrocyte response to fava bean ingestion in G6PD-deficient mice.

BACKGROUND: Favism is an acute hemolytic syndrome caused by fava bean (FB) ingestion. The purpose of this study was to investigate the possible influences of FB on the metabonomic profile of erythrocytes in glucose-6-phosphate dehydrogenase (G6PD)-deficient (G6PDx) and wild-type (WT) mice. RESULTS: Ninety-two metabolites were identified in the comparison of the G6PDx and WT groups. Eighty-seven metabolites were identified in the erythrocytes of WT and G6PDx mice after FB ingestion. Thirty-eight metabolites were identified in the comparison of the FB-treated G6PDx and the FB-treated WT mouse groups. Among them, the number of glycerophospholipids (GPLs) and polyunsaturated fatty acids (PUFAs) changed significantly, which suggests that GPLs and PUFAs may be responsible for FB stress. CONCLUSION: This study demonstrates that G6PD deficiency might affect the metabonomic profile of erythrocytes in response to FB. © 2020 Society of Chemical Industry.

Effects of exercise frequency on the gut microbiota in elderly individuals.

Growing evidence has shown that exercise can affect the gut microbiota. The effects of exercise frequency on the gut microbiota in elderly individuals are still largely unknown. In the present study, samples from 897 elderly and 1,589 adult individuals (18-60 years old) from the American Gut Project were screened. Microbial diversity and composition were analyzed by QIIME2, and microbial function was predicted by PICRUSt2. The outcomes were further analyzed by STAMP. The analysis showed that the α-diversity of gut microbiota increased with increasing age, and regular exercise reshaped the alterations in microbial composition and function induced by aging. Moreover, the α-diversity of gut microbiota was higher in overweight elderly individuals than in normoweight elderly individuals, and regular exercise significantly affected the microbial composition and function in overweight elderly individuals. In conclusion, we revealed that regular exercise benefits elderly individuals, especially overweight elderly individuals, by modulating the gut microbiota.

Vitamin B and vitamin D as modulators of gut microbiota in overweight individuals.

Growing evidence indicates that vitamin B (VB) and vitamin D (VD) are associated with the development of obesity. The effects of supplemental dietary VB and VD on the gut microbiota of obese individuals are still largely unknown. In the present study, 997 normoweight (NW) and 773 overweight (OW) samples were screened from the American Gut Project. The microbial α-diversity was not affected by VB, VD or VB combined with VD (VBD) supplementation in the normoweight population or the overweigh population. VD significantly modulated 20 gut microbial metabolic pathways in NW. Moreover, VBD supplementation significantly affected 3 phyla and 3 families and 22 pathways in the OW gut microbiota. In summary, our results highlight that VD and VBD might be necessary for reshaping the gut microbiota in NW and OW, respectively.

Intestinal transcriptional profiling reveals fava bean-induced immune response in DBA/1 mice.

BACKGROUND: Fava beans (FBs) have long been used as food, and their principal disadvantage is derived from their haemotoxicity. We hypothesized that FB ingestion alters the intestinal gene expression pattern, thereby inducing an immune response. RESULTS: In-depth sequence analysis identified 769 differentially expressed genes (DEGs) associated with the intestine in FB-treated DBA/1 mouse intestines. The identified genes were shown to be associated with biological processes (such as response to stimulus and immune system processes), human disease pathways (such as infectious diseases, endocrine and metabolic diseases, and immune diseases), and organismal system pathways (such as the digestive system, endocrine system, environmental adaptation, and immune system). Moreover, plasma total immunoglobulin E (IgE), histamine, interleukin (IL)-4 and IL-13 levels were significantly increased when the mice were treated with FBs. CONCLUSIONS: These results demonstrated that FBs affect the intestinal immune response and IgE and cytokine secretion in DBA/1 mice.

Intestinal transcriptional profiling reveals fava bean-induced immune response in DBA/1 mice

BACKGROUND: Fava beans (FBs) have long been used as food, and their principal disadvantage is derived from their haemotoxicity. We hypothesized that FB ingestion alters the intestinal gene expression pattern, thereby inducing an immune response. RESULTS: In-depth sequence analysis identified 769 differentially expressed genes (DEGs) associated with the intestine in FB-treated DBA/1 mouse intestines. The identified genes were shown to be associated with biological processes (such as response to stimulus and immune system processes), human disease pathways (such as infectious diseases, endocrine and metabolic diseases, and immune diseases), and organismal system pathways (such as the digestive system, endocrine system, environmental adaptation, and immune system). Moreover, plasma total immunoglobulin E (IgE), histamine, interleukin (IL)-4 and IL-13 levels were significantly increased when the mice were treated with FBs. CONCLUSIONS: These results demonstrated that FBs affect the intestinal immune response and IgE and cytokine secretion in DBA/1 mice.

[Mesenchymal Stem Cells Stimulated by Growth Factors Release Exosomes with Potent Proangiogenic Activity].

OBJECTIVE: To explore the proangiogenic activity of exsomes released by human umbilical cord mesenchymal stem cells (MSCs) stimulated by erythropoietin and platelet-derived growth factor BB (PDGF-BB). METHODS: Human umbilical cord-derived MSCs were seeded and maintained in culture overnight. The media were then replaced by alpha-MEM containing EPO (1 U/ml) and/or PDGF-BB (50 ng/ml), and the culture was maintained for 72 hours. The exosomes from the culture supernatants were isolated with a routine ultra-catrifagation method. Flow cytometric analysis was performed to identify the origin of the exosomes, and their morphological features were observed by using a transmission electron microscopy. The exosomes were added at a concentration of 10 µg/ml into the culture system of human umbilical cord vein endothelial cells. MTT assay was used to evaluate the proliferative status. The Matrigel assay was used to observe the formation of net-work structures which were calculated after culture for 12 hours. RESULTS: Flow cytometric analysis showed that microparticles released by human umbilical cord MSCs expressed CD9, CD63 and CD81, which was in accordance with the surface molecular features of exosomes. Under an electron microscope, the exosomes took the featured cystic shape. The protein contents of exosomes released by untreated, EPO-stimulated, PDGF-BB-stimulated and EPO plus PDGF-BB stimulated MSCs (108 cells) were 256±124 µg, 1021±392 µg, 830±265 µg and 2207±733 µg, respectively. The results revealed that MSCs treated by EPO and PDGF-BB released significantly higher amounts of exosomes (P<0.01). MTT assay proved that the exosomes from EPO and PDGF-BB treated MSCs had more potent proliferation-promoting activity on human umbilical cord vein endothelial cells than those from untreated MSCs. The Matrigel assay showed that the numbers of capillary-like structures in untreated, EPO-, PDGF-BB and EPO plus PDGF-BB-treated groups were 2.6±0.84, 4.6±1.57, 4.2±0.78 and 6.3±1.34 per high power objective. Treatment with EPO or PDGF-BB dramatically enhanced the numbers of capillary liue structure, compared with that of untreated group (P<0.01) and those in EPO and PDGF-BB combination group was significantly greater than those of EPO or PDGF-BB group (P<0.01). CONCLUSION: EPO and PDGF-BB can stimulate MSCs to release exosomes with more potent proangiogenic activity.

Brain Natriuretic Peptide and Its Biochemical, Analytical, and Clinical Issues in Heart Failure: A Narrative Review.

Heart failure (HF) is a primary cause of morbidity and mortality worldwide. As the most widely studied and commonly applied natriuretic peptide (NP), B-type natriuretic peptide (BNP) has the effects of diuresis, natriuresis, vasodilation, anti-hypertrophy, and anti-fibrosis and it inhibits the renin-angiotensin-aldosterone and sympathetic nervous systems to maintain cardiorenal homeostasis and counteract the effects of HF. Both BNP and N-terminal pro B-type natriuretic peptide (NT-proBNP) are applied as diagnostic, managing, and prognostic tools for HF. However, due to the complexity of BNP system, the diversity of BNP forms and the heterogeneity of HF status, there are biochemical, analytical, and clinical issues on BNP not fully understood. Current immunoassays cross-react to varying degrees with pro B-type natriuretic peptide (proBNP), NT-proBNP and various BNP forms and cannot effectively differentiate between these forms. Moreover, current immunoassays have different results and may not accurately reflect cardiac function. It is essential to design assays that can recognize specific forms of BNP, NT-proBNP, and proBNP to obtain more clinical information. Not only the processing of proBNP (corin/furin) and BNP (neprilysin), but also the effects of glycosylation on proBNP processing and BNP assays, should be targeted in future studies to enhance their diagnostic, therapeutic, and prognostic values.

Prognostic value of plasma NT-proBNP levels in very old patients with moderate renal insufficiency in China.

BACKGROUND: The N­terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value in chronic renal insufficiency; however, most studies have been conducted in patients with end-stage renal disease (ESRD). In this study we evaluated the prognostic significance of NT-proBNP in very old patients with stage 3 chronic kidney disease (CKD) and compared its prognostic value in CKD3a versus CKD3b patients. METHODS: Patients (age ≥80 years old) hospitalized with stage 3 CKD from 2007 to 2010 who were eligible for this prospective study underwent follow-up examinations in 2015. The examinations included measurements of anthropometric characteristics, blood pressure, plasma NT-proBNP, creatinine, and lipids. End-point events were all-cause death and major adverse cardiac events (MACEs). RESULTS: A total of 168 patients (mean age 87.4 ± 2.9 years, range 80-99 years) were included in the analysis (CKD3a, n = 117; CKD3b, n = 51). The results showed that CKD3b was associated with lower hemoglobin levels, higher NT-proBNP levels and a higher rate of hypertension compared with CKD3a. After a median follow-up of 3.8 years (interquartile range 1.5-6.1 years), a higher NT-proBNP level was associated with a higher risk of all-cause death (hazard ratio HR 1.986, 95% confidence interval CI 1.276-2.819, p = 0.028) and MACEs (HR 2.872, 95% CI 1.241-6.644, p = 0.014) after adjusting for age, sex, and traditional risk factors; however, a subgroup comparison showed that elevated NT-proBNP levels were associated with a higher risk of all-cause death (HR 2.350, 95% CI 1.906-6.091, p = 0.039) and MACEs (HR 3.025, 95% CI 1.024-8.940, p = 0.045) in CKD3a but not CKD3b. CONCLUSION: Levels of NT-proBNP increased with decreased renal function in very old patients with stage 3 CKD; therefore, NT-proBNP is an independent predictor for all-cause death and MACEs in these patients but has a greater prognostic value in CKD3a than in CKD3b.

Cancer risk in older people receiving statin therapy: a meta-analysis of randomized controlled trials.

BACKGROUND: Although statins are well tolerated by most aged people, their potential carcinogenicity is considered as one of the biggest factors limiting the use of statins. The aim of the present study was to determine the risk of cancer in people aged over 60 years receiving statin therapy. METHODS: A comprehensive search for articles published up to December 2015 was performed, reviews of each randomized controlled trials (RCTs) that compared the effects of statin mono-therapy with placebo on the risk of cancer in people aged > 60 years were conducted and data abstracted. All the included studies were evaluated for publication bias and heterogeneity. Pooled odds ratios (OR) estimates and 95% confidence intervals (CIs) were calculated using the random effects model. RESULTS: A total of 12 RCTs, involving 62,927 patients (31,517 in statin therapy group and 31,410 in control group), with a follow-up duration of 1.9-5.4 years, contributed to the analysis. The statin therapy did not affect the overall incidence of cancer (OR = 1.03, 95% CI: 0.94-1.14, P = 0.52); subgroup analyses showed that neither the variety nor the chemical properties of the statins accounted for the incidence of cancer in older people. CONCLUSIONS: Our meta-analysis findings do not support a potential cancer risk of statin treatment in people over 60 years old. Further targeted researches with a longer follow-up duration are warranted to confirm this issue.

The prognostic value of the plasma N-terminal pro-brain natriuretic peptide level on all-cause death and major cardiovascular events in a community-based population.

BACKGROUND: Despite growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value for patients with cardiovascular disease, chronic kidney disease, etc, the prognostic significance of NT-proBNP levels in the general population has not been established. The aim of this study was to evaluate the clinical significance of NT-proBNP in a community population. METHODS: This is a community-based prospective survey of residents from two communities in Beijing conducted for a routine health status checkup. Out of 1,860 individuals who were eligible for inclusion from 2007 to 2009, 1,499 completed a follow-up and were assessed for the prognostic value of NT-proBNP in 2013. A questionnaire was used for end point events. Anthropometry and blood pressure were measured. Plasma NT-proBNP, creatinine, lipids, and glucose were determined. RESULTS: A total of 1,499 subjects with complete data were included in the analysis. Participants were divided into four groups according to baseline NT-proBNP levels (quartile 1, <19.8 pg/mL; quartile 2, 19.8-41.6 pg/mL; quartile 3, 41.7-81.8 pg/mL; quartile 4, ≥81.9 pg/mL). During a median 4.8-year follow-up period, the all-cause mortality rate rose from 0.8% in the lowest concentration NT-proBNP group (<19.8 pg/mL) to 7.8% in the highest NT-proBNP group (≥81.9 pg/mL; P<0.001). The incidence of major adverse cardiovascular events (MACEs) increased from 3.1% in the lowest NT-proBNP group to 18.9% in the highest group (P<0.001). Individuals in the highest NT-proBNP group (≥81.9 pg/mL) were associated with higher risk of all-cause death and MACEs compared with the lowest NT-proBNP group using Kaplan-Meier survival curves and the Cox proportional hazard model after adjusting for age, sex, and traditional risk factors. CONCLUSION: The plasma NT-proBNP level is a strong and independent prognosis factor for all-cause death and MACEs in the community population. The NT-proBNP cut-point for the prognostic value remains to be further studied. NT-proBNP is a strong and independent prognostic factor for all-cause death and MACEs in individuals older than 65 years and MACEs in individuals younger than 65 years.