The Role of MMP-9 in Regulating Degradation of the Splenic Microvascular Basement Membrane Induced by High Altitude Hypoxia / Rol de la MMP-9 en la Regulación de la Degradación de la Membrana Basal Microvascular Esplénica Inducida por Hipoxia de Altura

SUMMARY: To investigate changes of MMP-9 in the rat spleen and hypoxia-induced microvascular basement membrane under high altitude hypoxia. Thirty male specific pathogen-free Sprague Dawley rats were randomly divided into control and hypoxia groups, with 15 rats in each group. The rats in the control group were placed in Dingxi City, Gansu Province (2080 m above sea level) for 30 days. Rats in the hypoxia group were raised in a hypoxic environment in Maduo County, Qinghai Province (4300 m above sea level), for 30 days to establish a hypoxic rat model. Routine blood tests, MMP-9 mRNA, MMP-9 protein, and the spleen microvascular basement membrane were detected. (1) Compared with the control group, the red blood cell count, hemoglobin, and hematocrit levels of the rats in the hypoxia group were all increased; thus, a hypoxia model was successfully established. (2) Compared with the control group, the expression of MMP-9 mRNA and protein was significantly higher in the spleen of rats in the hypoxic group, and the difference was statistically significant (P <0.05). (3) Compared with the control group, the blood vessel basement membrane in the spleen of the hypoxia group was degraded. Under natural low air pressure and high altitude conditions, the expression of MMP-9 in rat spleen tissue increases and participates in the degradation of the microvascular basement membrane.

El objetivo de este trabajo fue investigar los cambios de la MMP-9 en el bazo de la rata y la membrana basal microvascular inducida bajo hipoxia a gran altura. Treinta ratas macho Sprague Dawley, libres de patógenos específicos, se dividieron aleatoriamente en dos grupos de 15 ratas cada uno, un grupo control y un grupo hipoxia. Durante 30 días las ratas del grupo control estuvieron en la ciudad de Dingxi, provincia de Gansu (2080 m sobre el nivel del mar). Las ratas del grupo de hipoxia se criaron en un entorno hipóxico en el condado de Maduo, provincia de Qinghai (4300 m sobre el nivel del mar), durante 30 días para establecer un modelo de rata hipóxica. Se realizaron análisis de sangre de rutina, ARNm de MMP-9, proteína MMP-9 y de la membrana basal microvascular del bazo. En comparación con el grupo control, el recuento de glóbulos rojos, la hemoglobina y los niveles de hematocrito de las ratas del grupo de hipoxia aumentaron; por lo tanto, se estableció con éxito un modelo de hipoxia. En comparación con el grupo control, la expresión de ARNm y proteína de MMP-9 fue significativamente mayor en el bazo de las ratas del grupo hipóxico, siendo la diferencia estadísticamente significativa (P <0,05). En comparación con el grupo control, la membrana basal de los vasos sanguíneos estaba degradada en el bazo del grupo hipoxia. En condiciones naturales de baja presión atmosférica y gran altitud, la expresión de MMP-9 en el tejido del bazo de la rata aumenta y participa en la degradación de la membrana basal microvascular.

Initial invasive versus conservative management of stable ischemic heart disease patients with a history of heart failure or left ventricular dysfunction: Insights from the ISCHEMIA trial

Background: It is unknown whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in patients with a history of heart failure (HF) or left ventricular dysfunction (LVD) when EF >35%, but <45%. Methods: Among 5179 participants randomized into the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA), all of whom had LVEF >35%, we compared cardiovascular outcomes by treatment strategy in those with a history of HF or LV dysfunction (HF/LVD) at baseline versus those without HF/LVD. Median follow up was 3.2 years. Results: There were 398 (7.7%) participants with HF/LVD at baseline of whom 177 had HF/LVEF>45%, 28 had HF/LVEF 35-45% and 193 had LVEF 35-45% but no prior history of HF. HF/LVD was associated with more comorbidities at baseline, particularly prior myocardial infarction (MI), stroke and hypertension. Compared to those without HF/LVD, those with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal MI, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest; four-year cumulative incidence rate (22.7% vs. 13.8%), cardiovascular death or MI (19.7% vs. 12.3%), and all-cause death or HF (15.0% vs. 6.9%). Those with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% vs. 29.3%, difference in 4- year event rate -12.1%; 95% CI: -22.6, -1.6%), whereas those without HF/LVD did not (13.0% vs. 14.6%, difference in 4-year event rate -1.6%; 95% CI: -3.8%, 0.7%; p-interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and CV mortality when invasive versus conservative strategy associated outcomes were analyzed with LVEF as a continuous variable for those with and without prior HF. Conclusions: ISCHEMIA trial participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35-45%, an initial invasive approach was associated with a better event-free survival. This result should be considered hypothesis generating.

Outcomes of chronic total occlusions in coronary arteries according to three therapeutic strategies: a meta-analysis with 6985 patients from 8 published observational studies

Abstract Objective: To perform a systematic review and meta-analysis of studies comparing coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical treatment (MT) in patients with chronic total occlusions (CTOs). Methods: We identified eligible observational studies published in the China National Knowledge Infrastructure database, PubMed, Excerpta Medica database, Google Scholar, Cochrane Library, Web of Science, and "Clinical trials" registration from 1999 to October 2018. Main outcome measures were all-cause mortality, cardiac death, major adverse cardiac events (MACEs), and myocardial infarction (MI). Results: There were eight observational studies including 6985 patients. Patients' mean age was 64.4 years. Mean follow-up time was 4.3 years. Comparing with MT (2958 patients), PCI (3157 patients) presented decreased all-cause mortality (odd ratio [OR]: 0.46, 95% confidence interval [CI]: 0.36-0.60; P<0.001), cardiac death (OR: 0.40, 95% CI: 0.31-0.52; P<0.001), MACE (OR: 0.55, 95% CI: 0.43-0.71; P<0.001), and MI (OR: 0.40, 95% CI: 0.26-0.62; P<0.001). Comparing with MT, CABG (613 patients) presented lower all-cause mortality (OR: 0.50, 95% CI: 0.36-0.69; P<0.001) and MACE (OR: 0.50, 95% CI: 0.26-0.96; P=0.04), but not lower MI (OR: 0.23, 95% CI: 0.03-1.54; P=0.13) and cardiac death (OR: 0.83, 95% CI: 0.51-1.35). Comparing with CABG, PCI did not present decreased risk for those outcomes. Conclusions: PCI or CABG was associated with better clinical outcome in patients with CTO than MT. PCI is not better than CABG in decreasing mortality, MI, cardiac death, and MACE in coronary CTO patients.

Outcomes of Chronic Total Occlusions in Coronary Arteries According to Three Therapeutic Strategies: A Meta-analysis with 6985 Patients from 8 Published Observational Studies.

OBJECTIVE: To perform a systematic review and meta-analysis of studies comparing coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical treatment (MT) in patients with chronic total occlusions (CTOs). METHODS: We identified eligible observational studies published in the China National Knowledge Infrastructure database, PubMed, Excerpta Medica database, Google Scholar, Cochrane Library, Web of Science, and "Clinical trials" registration from 1999 to October 2018. Main outcome measures were all-cause mortality, cardiac death, major adverse cardiac events (MACEs), and myocardial infarction (MI). RESULTS: There were eight observational studies including 6985 patients. Patients' mean age was 64.4 years. Mean follow-up time was 4.3 years. Comparing with MT (2958 patients), PCI (3157 patients) presented decreased all-cause mortality (odd ratio [OR]: 0.46, 95% confidence interval [CI]: 0.36-0.60; P<0.001), cardiac death (OR: 0.40, 95% CI: 0.31-0.52; P<0.001), MACE (OR: 0.55, 95% CI: 0.43-0.71; P<0.001), and MI (OR: 0.40, 95% CI: 0.26-0.62; P<0.001). Comparing with MT, CABG (613 patients) presented lower all-cause mortality (OR: 0.50, 95% CI: 0.36-0.69; P<0.001) and MACE (OR: 0.50, 95% CI: 0.26-0.96; P=0.04), but not lower MI (OR: 0.23, 95% CI: 0.03-1.54; P=0.13) and cardiac death (OR: 0.83, 95% CI: 0.51-1.35). Comparing with CABG, PCI did not present decreased risk for those outcomes. CONCLUSIONS: PCI or CABG was associated with better clinical outcome in patients with CTO than MT. PCI is not better than CABG in decreasing mortality, MI, cardiac death, and MACE in coronary CTO patients.

Clinical Significance of Cys-C and hs-CRP in Coronary Heart Disease Patients Undergoing Percutaneous Coronary Intervention.

OBJECTIVE: To investigate the clinical significance of serum cystatin C (Cys-C) and high-sensitivity C-reactive protein (hs-CRP) in coronary heart disease (CHD) patients undergoing percutaneous coronary intervention (PCI). METHODS: One hundred and twenty-eight CHD patients were divided into drug treatment (56 cases) and PCI treatment (72 cases) groups, receiving conventional drug treatment and PCI plus conventional drug treatment, respectively. At admission time and 4 weeks after treatment, the left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter, and left ventricular end systolic diameter were measured. At admission time and 24h, 72h, 1 week, and 4 weeks after treatment, the serum levels of Cys-C and hs-CRP were determined. RESULTS: After 4 weeks of treatment, LVEF in the PCI treatment group was significantly higher than that before treatment (P<0.01) and it was significantly higher than in the drug treatment group at the same time (P<0.01). Cys-C and hs-CRP level in the PCI treatment group were significantly higher than in the drug treatment group 72h and 1 week after treatment (P<0.05 or P<0.01), respectively, but they were significantly lower than in the drug treatment group 4 weeks after treatment (P<0.01). There were obvious interaction effects between grouping factor and time factor in Cys-C (F=3.62, P<0.05) and hs-CRP (F=17.85, P<0.01). CONCLUSION: Serum levels of Cys-C and hs-CRP are closely related to the heart function in CHD patients undergoing PCI, and they may be used for predicting the outcome of PCI.

Clinical significance of cys-c and hs-crp in coronary heart disease patients undergoing percutaneous coronary intervention

Abstract Objective: To investigate the clinical significance of serum cystatin C (Cys-C) and high-sensitivity C-reactive protein (hs-CRP) in coronary heart disease (CHD) patients undergoing percutaneous coronary intervention (PCI). Methods: One hundred and twenty-eight CHD patients were divided into drug treatment (56 cases) and PCI treatment (72 cases) groups, receiving conventional drug treatment and PCI plus conventional drug treatment, respectively. At admission time and 4 weeks after treatment, the left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter, and left ventricular end systolic diameter were measured. At admission time and 24h, 72h, 1 week, and 4 weeks after treatment, the serum levels of Cys-C and hs-CRP were determined. Results: After 4 weeks of treatment, LVEF in the PCI treatment group was significantly higher than that before treatment (P<0.01) and it was significantly higher than in the drug treatment group at the same time (P<0.01). Cys-C and hs-CRP level in the PCI treatment group were significantly higher than in the drug treatment group 72h and 1 week after treatment (P<0.05 or P<0.01), respectively, but they were significantly lower than in the drug treatment group 4 weeks after treatment (P<0.01). There were obvious interaction effects between grouping factor and time factor in Cys-C (F=3.62, P<0.05) and hs-CRP (F=17.85, P<0.01). Conclusion: Serum levels of Cys-C and hs-CRP are closely related to the heart function in CHD patients undergoing PCI, and they may be used for predicting the outcome of PCI.

Cause of death among infants in rural western China: a community-based study using verbal autopsy.

OBJECTIVES: To determine the causes of death among infants in high-mortality areas of western China with the use of globally recognized methods. STUDY DESIGN: A survey of all infant deaths identified over 1 year in 4 counties in Yunnan and Xinjiang in which combined verbal autopsy was combined with a physician's diagnosis of the cause to calculate the local infant mortality rate. RESULTS: Among 470 completed investigations, a cause of death was assigned to 423 cases (90%). Overall, pneumonia (34.5%), preterm birth complications (16.5%), diarrhea (10.4%), birth asphyxia (10.3%), and congenital abnormalities (8.5%) were the main causes, with 56.6% of deaths occurring in the neonatal period. Deaths were attributable predominantly to prematurity or birth asphyxia in the early neonatal period, whereas infection accounted for more than 60% and 80% of deaths in the late and postneonatal periods, respectively. Calculated infant mortality was 21.9 in 1000 live births. CONCLUSIONS: The pattern of infant mortality observed in the surveyed counties differs markedly from that reported previously at the national level, with a high proportion the result of causes that may be preventable with globally recommended interventions. Financial and political support is needed to promote improved cause of death surveillance and newborn and infant health care in China's western region.