Abstract Aplastic anemia (AA), a rare disorder, is associated with bone marrow microenvironment (BMM). Presently, AA treatment is of great difficulty. This study aimed to explore the mechanism of action of Rehmannia glutinosa polysaccharide (RGP) in AA. Busulfan was used to induce AA in BALB/c mice; blood cell count and Ray’s Giemsa staining were used to assess the severity of hematopoietic failure; HE was performed to assess the pathological state of the marrow cavity; ELISA was performed to assess IL-4, IL-10, IL-6, IL-12, IL-1β, TNF-α, MCP-1, VEGF, and EPO; and WB was performed to evaluate the effects of RGP on the HIF-1α/NF-κB signaling. Significant downregulation of hemocyte levels in the blood and nucleated cells in the bone marrow was reversed by RGP and Cyclosporine A (CA). Compared with the AA group, dilating blood sinusoids, inflammation, hematopoiesis, decreased bone marrow cells and megakaryocytes were alleviated by RGP and CA, and the HIF-1α/NF-κB signaling was inhibited too. Notably, RGP was more effective when used in combination with CA. In this study, we established a relationship between BMM and the HIF-1α/NF-κB signaling pathway and found that RGP regulates BMM by suppressing the activation of the HIF-1α/NF-κB signaling. Thus, RGP exerts a pharmacological effect on AA.

ABSTRACT Introduction: Pulmonary artery denervation (PADN) can reduce the sympathetic nervous system (SNS) activity, reduce pulmonary artery pressure (PAP), and improve the quality of life in patients with pulmonary hypertension (PH). We conducted a systematic meta-analysis of the effectiveness of PADN in the treatment of PH patients. Methods: This is a comprehensive literature search including all public clinical trials investigating the effects of PADN on PH. Outcomes were mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac output (CO), right ventricular (RV) Tei index, 6-minute walk distance (6MWD), and New York Heart Association (NYHA) cardiac function grading. Results: A total of eight clinical studies with 213 PH patients who underwent PADN were included. Meta-analysis showed that after PADN, mPAP (mean difference [MD] -12.51, 95% confidence interval [CI] -17.74 to -7.27, P<0.00001) (mmHg) and PVR (MD -5.17, 95% CI -7.70 to -2.65, P<0.0001) (Wood unit) decreased significantly, CO (MD 0.59, 95% CI 0.32 to 0.86, P<0.0001) (L/min) and 6MWD (MD 107.75, 95% CI 65.64 to 149.86, P<0.00001) (meter) increased significantly, and RV Tei index (MD -0.05, 95% CI -0.28 to 0.17, P=0.63) did not change significantly. Also after PADN, the proportion of NYHA cardiac function grading (risk ratio 0.23, 95% CI 0.14 to 0.37, P<0.00001) III and IV decreased significantly. Conclusion: This meta-analysis supports PADN as a potential new treatment for PH. Further high-quality randomized controlled studies are needed.

OBJECTIVES: TTP488, an antagonist of the receptor for advanced glycation end-products, was evaluated as a potential treatment for patients with mild-to-moderate Alzheimer’s disease (AD). However, the mechanism underlying the protective action of TTP488 against AD has not yet been fully explored. METHODS: Healthy male rats were exposed to aberrant amyloid β (Aβ) 1-42. Lipopolysaccharide (LPS) and the NOD-like receptor family pyrin domain containing 1 (NLRP1) overexpression lentivirus were injected to activate the NLRP1 inflammasome and exacerbate AD. TTP488 was administered to reverse AD injury. Finally, tofacitinib and fludarabine were used to inhibit the activity of Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) to prove the relationship between the JAK/STAT signaling pathway and TTP488. RESULTS: LPS and NLRP1 overexpression significantly increased the NLRP1 levels, reduced neurological function, and aggravated neuronal damage, as demonstrated by the impact latency time of, time spent by, and length of the platform covered by, the mice in the Morris water maze assay, Nissl staining, and immunofluorescence staining in rats with AD. CONCLUSIONS: TTP488 administration successfully reduced AD injury and reversed the aforementioned processes. Additionally, tofacitinib and fludarabine administration could further reverse AD injury after the TTP488 intervention. These results suggest a new potential mechanism underlying the TTP488-mediated alleviation of AD injury.

Resumo Fundamento: A carga trombótica intracoronária durante a intervenção coronária percutânea primária em pacientes com Infarto com Supradesnivelamento do Segmento ST (STEMI) pode levar a resultados negativos.Os monócitos foram descritos para desempenhar um papel importante nos distúrbios trombóticos. Objetivos: Este estudo investigou a relação entre a contagem de monócitos no momento da internação e a carga trombótica angiográfica intracoronária em pacientes submetidos à intervenção coronária percutânea primária (ICPP). Métodos: Um total de 273 pacientes com STEMI agudo submetidos à ICPP participaram. Os pacientes se dividiram em dois grupos de acordo com o grau trombótico na trombólise do infarto do miocárdio (TIMI): grupo baixa carga trombótica, com graus de 0-2, e grupo alta carga trombótica, com graus de 3-4. A contagem de monócitos e outros parâmetros laboratoriais foram medidos na internação antes da ICPP. Consideramos o valor de p < 0,05 significativo. Resultados: Havia 95 pacientes (34,8%) no grupo alta carga trombótica, e 178 pacientes (65,2%) no grupo baixa carga trombótica. Pacientes com alta carga trombótica apresentaram contagem de monócitos no momento da internação mais alta (0,61 ± 0,29×109/L vs. 0,53 ± 0,24×109/L, p = 0,021). Na análise multivariada, a contagem de monócitos foi o indicador independente da alta carga trombótica angiográfica (odds ratio 3,107, intervalo de confiança de 95% [IC] 1,199-7,052, p = 0,020). Para a previsão da alta carga trombótica angiográfica, a contagem de monócitos na internação tinha ponto de corte de 0,48×109/L, chegou a 0.59 ROC-AUC (71,9% sensibilidade, 46,9% especificidade). Conclusões: a contagem de monócitos na internação foi um indicador clínico independente da alta carga trombótica em pacientes com STEMI submetidos à ICPP. Nossos achados sugerem que a contagem de monócitos na internação pode estar disponível para a estratificação de risco precoce da alta carga trombótica em pacientes com STEMI agudo, e podem levar à otimização da terapia antitrombótica para melhorar os resultados da ICPP.

Abstract Background: The intracoronary high-thrombus burden during the primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction (STEMI) can lead to poor outcomes. Monocytes have been described to play an important role in thrombotic disorders. Objectives: This study aimed to investigate the relationship between admission monocyte count and angiographic intracoronary thrombus burden in patients receiving primary percutaneous coronary intervention (PPCI). Methods: A total of 273 patients with acute STEMI who underwent PPCI were enrolled. The patients were divided into two groups according to the thrombolysis in myocardial infarction (TIMI) thrombus grade: low-thrombus burden group with a grade of 0-2 and high-thrombus burden group with a grade of 3-4. The monocyte count and other laboratory parameters were measured on admission before PPCI. P-value < 0.05 was considered significant. Results: There were 95 patients (34.8%) in the high-thrombus burden group, and 178 patients (65.2%) in the low-thrombus burden group. Patients with high-thrombus burden had significantly higher admission monocyte count (0.61 ± 0.29×109/L vs. 0.53 ± 0.24×109/L, p = 0.021). In multivariate analysis, monocyte count was the independent predictor of angiographic high-thrombus burden (odds ratio 3.107, 95% confidence interval [CI] 1.199-7.052, p = 0.020). For the prediction of angiographic high-thrombus burden, admission monocyte count at a cut-off value of 0.48×109/L yielded 0.59 ROC-AUC (71.9% sensitivity, 46.9% specificity). Conclusions: Monocyte count on admission was an independent clinical predictor of high-thrombus burden in patients with STEMI undergoing PPCI. Our findings suggest that admission monocyte count may be available for early risk stratification of high-thrombus burden in acute STEMI patients and might allow the optimization of antithrombotic therapy to improve the outcomes of PPCI.

Reference genes are commonly used for normalization of target gene expression during RT-qPCR analysis. However, no housekeeping genes or reference genes have been identified to be stable across different tissue types or under different experimental conditions. To identify the most suitable reference genes for RT-qPCR analysis of target gene expression in the hepatopancreas of crucian carp (Carassius auratus) under various conditions (sex, age, water temperature, and drug treatments), seven reference genes, including beta actin (ACTB), beta-2 microglobulin (B2M), embryonic elongation factor-1 alpha (EEF1A), glyceraldehyde phosphate dehydrogenase (GAPDH), alpha tubulin (TUBA), ribosomal protein l8 (RPL8) and glucose-6-phosphate dehydrogenase (G6PDH), were evaluated in this study. The stability and ranking of gene expression were analyzed using three different statistical programs: GeNorm, Normfinder and Bestkeeper. The expression errors associated with selection of the genes were assessed by the relative quantity of CYP4T. The results indicated that all the seven genes exhibited variability under the experimental conditions of this research, and the combination of ACTB/TUBA/EEF1A or of ACTB/EEF1A was the best candidate that raised the accuracy of quantitative analysis of gene expression. The findings highlighted the importance of validation of housekeeping genes for research on gene expression under different conditions of experiment and species.

OBJECTIVE:The goal of the present study was to compare the prognoses of patients with non-ST-elevation acute coronary syndromes who were treated with invasive or conservative treatment strategies.METHODS:We performed a meta-analysis of studies of patients with non-ST-elevation acute coronary syndromes to assess the benefits of an invasive strategy vs. a conservative strategy for short- and long-term survival. We searched PubMed for studies published from 1990 to November 2012 that investigated the effects of an invasive vs. conservative strategy in patients with non-ST-elevation acute coronary syndromes. The following search terms were used: “non-ST-elevation myocardial infarction”, “unstable angina”, “acute coronary syndromes”, “invasive strategy”, and “conservative strategy”. The primary endpoints were all-cause mortality at 30 days and 1 year.RESULTS:Seven published studies were included in the present meta-analysis. The pooled analyses show that an invasive strategy decreased the risk of death (risk ratio [0.839] [95% confidence interval {0.648-1.086}; I2, 86.46%] compared to a conservative strategy over a 30-day-period. Furthermore, invasive treatment also decreased patient mortality (risk ratio [0.276] [95% confidence interval {0.259-0.294}; I2, 94.58%]) compared to a conservative strategy for one year.CONCLUSION:In non-ST-elevation acute coronary syndromes, an invasive strategy is comparable to a conservative strategy for decreasing short- and long-term mortality rates.

OBJECTIVE: To evaluate the effects of percutaneous coronary intervention and thrombolysis after restoration of spontaneous circulation in cardiac arrest patients with ST-elevation myocardial infarction using meta-analysis. METHODS: We performed a meta-analysis of clinical studies indexed in the PUBMED, MEDLINE and EMBASE databases and published between January 1995 and October 2012. In addition, we compared the hospital discharge and neurological recovery rates between the patients who received percutaneous coronary intervention and those who received thrombolysis. RESULTS: Twenty-four studies evaluating the effects of percutaneous coronary intervention or thrombolysis after restoration of spontaneous circulation in cardiac arrest patients with ST-elevation myocardial infarction were included. Seventeen of the 24 studies were used in this meta-analysis. All studies were used to compare percutaneous coronary intervention and thrombolysis. The meta-analysis showed that the rate of hospital discharge improved with both percutaneous coronary intervention (p<0.001) and thrombolysis (p<0.001). We also found that cardiac arrest patients with ST-elevation myocardial infarction who received thrombolysis after restoration of spontaneous circulation did not have decreased hospital discharge (p = 0.543) or neurological recovery rates (p = 0.165) compared with those who received percutaneous coronary intervention. CONCLUSION: In cardiac arrest patients with ST-elevation myocardial infarction who achieved restoration of spontaneous circulation, both percutaneous coronary intervention and thrombolysis improved the hospital discharge rate. Furthermore, there were no significant differences in the hospital discharge and neurological recovery rates between the percutaneous coronary intervention-treated group and the thrombolysis-treated group.