Exercise-Training Regulates Apolipoprotein B in Drosophila to Improve HFD-Mediated Cardiac Function Damage and Low Exercise Capacity.

Apolipoprotein B plays an essential role in systemic lipid metabolism, and it is closely related to cardiovascular diseases. Exercise-training can regulate systemic lipid metabolism, improve heart function, and improve exercise capacity, but the molecular mechanisms involved are poorly understood. We used a Drosophila model to demonstrate that exercise-training regulates the expression of apoLpp (a homolog of apolipoprotein B) in cardiomyocytes, thereby resisting heart insufficiency and low exercise capacity caused by obesity. The apoLpp is an essential lipid carrier produced in the heart and fat body of Drosophila. In a Drosophila genetic screen, low expression of apoLpp reduced obesity and cardiac dysfunction induced by a high-fat diet (HFD). Cardiac-specific inhibition indicated that reducing apoLpp in the heart during HFD reduced the triglyceride content of the whole-body and reduced heart function damage caused by HFD. In exercise-trained flies, the result was similar to the knockdown effect of apoLpp. Therefore, the inhibition of apoLpp plays an important role in HFD-induced cardiac function impairment and low exercise capacity. Although the apoLpp knockdown of cardiomyocytes alleviated damage to heart function, it did not reduce the arrhythmia and low exercise capacity caused by HFD. Exercise-training can improve this condition more effectively, and the possible reason for this difference is that exercise-training regulates climbing ability in ways to promote metabolism. Exercise-training during HFD feeding can down-regulate the expression of apoLpp, reduce the whole-body TG levels, improve cardiac recovery, and improve exercise capacity. Exercise-training can downregulate the expression of apoLpp in cardiomyocytes to resist cardiac function damage and low exercise capacity caused by HFD. The results revealed the relationship between exercise-training and apoLpp and their essential roles in regulating heart function and climbing ability.

The Change Trend of Cause of Death in Patients With Stage I Non-Small Cell Lung Cancer After Surgery in US: A Long-Term Follow-Up Study Based on SEER Database.

There are few studies on the cause of death in patients with stage I non-small cell lung cancer after surgery. Our aim is to study the trend of cause of death and risk factors affecting prognosis in the patients. We retrospectively reviewed patients in Surveillance, Epidemiology and End results database from 2004 to 2015. The change trend between cause of death and follow-up time was studied by calculating the proportion of cause of death at different periods and analyzing the cumulative risk. COX risk regression model was performed by univariate and multivariate analyses for survival analysis. Finally, 23,652 patients were enrolled. In the whole cohort, lung cancer accounted for 18.68% of deaths, followed by other causes (9.57%), heart disease (5.12%) and COPD (3.89%). With the increasing of follow-up time, the cumulative incidence of lung cancer was always the highest, but the growth rate in the late follow-up period was slower than that caused by heart disease and COPD. The proportion of death due to lung cancer decreased from 53.1%-73.1% in 0-30 months after follow-up to 7.8%-41.4% in 90 months after follow-up, while the proportion of deaths due to heart disease and COPD increased. Age was an independent risk factor for lung cancer-, heart disease- and COPD-specific survival, while lobectomy resection was a protective factor, even in patients older than 70 years old. In conclusion, during the follow-up period, lung cancer was still the main cause of death, but the proportion of patients died of heart disease and COPD increased gradually, especially in elderly. Furthermore, age was an important independent factor affecting prognosis, particularly for heart disease- and COPD-related mortality. The application of wedge resection in elderly patients needs further exploration.

Effects of adjuvant chemotherapy on survival of patients with stage IB non-small cell lung cancer with visceral pleural invasion.

BACKGROUND: Adjuvant chemotherapy could improve the prognosis of stage II-III non-small cell lung cancer (NSCLC). However, its influences on stage IB were controversial. The purpose of this study was to investigate whether patients with stage IB NSCLC could benefit from adjuvant chemotherapy. METHODS: Stage IB NSCLC in 2010-2015 was selected from the surveillance, epidemiology, and end result database. Chi square test was used to compare the clinical characteristics of patients with different adjuvant chemotherapy status. Kaplan-Meier survival curves were plotted by the log-rank test. Cox proportional hazard regression was used to perform multivariate analysis on overall survival (OS), and the life table method was employed to calculate 1-, 3-, and 5-year survival rates. RESULTS: A total of 2915 patients were included in this study, and the number of patients with visceral pleural invasion (VPI) was 1096 (37.6%), of which 145 (13.2%) received adjuvant chemotherapy. There was no statistical difference in OS among the total population with or without chemotherapy (p = 0.295), nor in patients with VPI (p = 0.216). In patients with VPI, the 1-, 3-, 5-year survival curves of patients who are receiving adjuvant chemotherapy showed an upward trend compared with patients who did not. Additionally, female, high differentiated, adenocarcinoma, and tumor size ≤ 3 cm were also independent prognostic factors for improving the prognosis of patients with VPI. CONCLUSION: In our study, stage IB NSCLC did not benefit from adjuvant chemotherapy, even in patients with VPI. However, the significance of adjuvant chemotherapy in patients with VPI is still worth further exploration.

CIH-induced neurocognitive impairments are associated with hippocampal Ca(2+) overload, apoptosis, and dephosphorylation of ERK1/2 and CREB that are mediated by overactivation of NMDARs.

Chronic intermittent hypoxia (CIH) is commonly seen in patients with obstructive sleep apnea, and has been hypothesized to underlie the neurocognitive dysfunction in these patients. However, its cellular and molecular mechanisms remain to be defined. The present study aimed to investigate, in a mouse CIH model, the role of NMDA receptor (NMDAR) activation in mediating the CIH-induced neurocognitive impairments, caspase expression and dysregulated Ca(2+) signaling pathways in hippocampus. Male ICR mice (n=45) were exposed to CIH (8h/day) or room air (control) for 4 weeks. After 4-week treatment, neurobehavioral assessments were performed by Morris water maze test, hippocampal [Ca(2+)]i was evaluated by flow cytometry; and protein expressions of caspase-3, caspase-9, PARP, p-ERK1/2 and p-CREB in hippocampus were measured by Western blotting. Our results showed that, compared to control animals, 4-week exposure to CIH produced significant spatial learning and memory impairments in CIH mice. Increased caspase expression in hippocampus was observed in CIH mice associated with significant elevation of [Ca(2+)]i and dephosphorylation of ERK and CREB expression. When the NMDAR antagonist memantine was administered by intraperitoneal injection prior to daily exposure to CIH, at a sub-therapeutic dose of 5mg/kg/day not shown to impact the neurobehavioral performance in control animals, the neurocognitive impairments as well as the neurobiochemical changes were abolished or normalized in the CIH mice. Our study suggests that overactivation of NMDARs and the Ca(2+) overload-dependent ERK/CREB dysregulation is one of the important mechanisms in mediating the CIH-induced neurocognitive impairments.

[Association between obesity and cognition impairment in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To explore the association between obesity and cognition impairment in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: A total of 425 eligible patients with moderate-to-severe OSAHS were screened for this retrospective study at Sleep Center, Second Affiliated Hospital, Soochow University from January 2008 to January 2013. Based on body mass index (BMI), they were categorized into normal weight (18.5 ≤ BMI<24, n = 67), mild overweight (24 ≤ BMI<26, n = 100), severe overweight (26 ≤ BMI<28, n = 134) and obese (BMI ≥ 28, n = 124) groups. They were examined by overnight polysomnography (PSG). And cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA) questionnaires. MoCA scores, clinical and polysomnographic variables were compared between the groups. And the correlations between MoCA scores and clinical and PSG parameters were further evaluated by stepwise multivariate regression. Two-way analysis of variance (two-way ANOVA) was performed to examine the effects of obesity and OSAHS on MoCA score. RESULTS: The scores of MoCA progressively decreased across the spectrum from mild overweight to obese groups. The highest BMI group (obese group) had the lowest MoCA score (25.45 ± 2.35 vs 26.26 ± 2.01, 26.29 ± 2.60, 26.05 ± 2.51, P = 0.030, 0.010, 0.048). The evaluations of MoCA subdomains further revealed selective reductions. Compare to normal weight group, the score of visuospatial and executive function, memory/delayed recall significant decreased in obese and severe overweight groups (visuospatial and executive function: 4.48 ± 0.63 vs 4.07 ± 0.94, 4.13 ± 1.04, P = 0.022, 0.048; memory/delayed recall: 3.54 ± 0.90 vs 2.77 ± 1.20, 2.87 ± 1.30, P = 0.001, 0.004). Stepwise multivariate regression analysis demonstrated that MoCA scores were correlated significantly with apnea-hypopnea index (AHI), BMI, age and years of education. Two-way ANOVA revealed that both obesity and OSAHS had independent effects on MoCA score (P = 0.004). The interactions between the effect of obesity and OSAHS on cognitive score were insignificant. It indicated that the effect of BMI on cognitive function did not change with AHI. CONCLUSIONS: In OSAHS patients, obesity aggravates cognitive impairment independently of AHI. And obesity is one of the most important influencing factors of cognitive function.