Helicobacter pylori (H. pylori) infection is related with a high risk of Alzheimer's disease (AD), but the intrinsic link between H. pylori infection and AD development is still missing. In the present study, we explored the effect of H. pylori infection on cognitive function and β-amyloid production in rats. We found that intraperitoneal injection of H. pylori filtrate induced spatial learning and memory deficit in rats with a simultaneous retarded dendritic spine maturation in hippocampus. Injection of H. pylori filtrate significantly increased Aβ42 both in the hippocampus and cortex, together with an increased level of presenilin-2 (PS-2), one key component of γ-secretase involved in Aβ production. Incubation of H. pylori filtrate with N2a cells which over-express amyloid precursor protein (APP) also resulted in increased PS-2 expression and Aβ42 overproduction. Injection of Escherichia coli (E.coli) filtrate, another common intestinal bacterium, had no effect on cognitive function in rats and Aβ production in rats and cells. These data suggest a specific effect of H. pylori on cognition and Aβ production. We conclude that soluble surface fractions of H. pylori may promote Aβ42 formation by enhancing the activity of γ-secretase, thus induce cognitive impairment through interrupting the synaptic function.
Background
The incidence rates of early-stage non-small cell lung cancer (NSCLC) are now increasing, and therapies such as thermal ablation have shown potential therapeutic promise. This study aimed to determine the influence of different surgical methods on overall survival (OS) and cancer-specific survival (CSS) in patients with stage I NSCLC.
Methods
Patients diagnosed with stage I NSCLC who had received thermal ablation or wedge resection between 2004 and 2014 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed according to the surgical method. Kaplan–Meier curves and a Cox proportional hazard model were used to evaluate OS and CSS.
Results
In all, 4,372 patients with stage I NSCLC were included. Before PSM, the respective 3- and 5-year OS rates were 68.9 and 52.7% in the wedge resection group and 68.5 and 47.8% in the thermal ablation group (
p
< 0.0001); the corresponding CSS rates were 79.1 and 69.4% and 62.6 and 46.0% (
p
< 0.0001). After PSM, survival analysis showed that wedge resection had better OS (44.5% vs. 30.1%,
p
= 0.033) and CSS (63.5% vs. 46%,
p
= 0.038) than thermal ablation. After PSM, Cox regression showed that treatment was not associated with OS or CSS. For patients aged >75 years, thermal ablation showed similar OS and CSS as wedge resection (OS: 30.6% vs. 41.7%,
p
= 0.470; CSS: 46.4% vs. 64.1%,
p
= 0.100). After PSM, thermal ablation still had OS (30.6% vs. 41.0%,
p
= 0.470) and CSS (46.4% vs. 59.8%,
p
= 0.100) comparable to wedge resection.
Conclusion
For patients with stage I NSCLC who are unfit for lobectomy, thermal ablation could be a potential therapeutic option, especially for those >75 years old.
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