Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial.

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

The role of physical activity on healthcare utilization in China.

BACKGROUND: Evidence on the role of physical activity (PA) on healthcare utilization and expenditure is limited in China. We aimed to examine the association between the total physical activity (TPA) per week, healthcare service use and expenditure. METHODS: We extracted the data from China Health and Retirement Longitudinal Study (CHARLS) 2011, 2013, and 2015. Participants more than 50 years old who completed the follow-up for the three waves were enrolled. We converted the volume of vigorous physical activity (VPA) into an equivalent volume of moderate physical activity (MPA) and calculated the TPA per week for each participant. 12,927 of the 17,708 participants in CHARLS were included in our analysis. More than one-third of participants over 50 years old never participate in any moderate or intensity activity, and the median of self-reported moderate or intensity PA was about 525 (IQR 0-1680) MET-minutes per week in 2015. RESULTS: Compared to inactive subjects, the highest level of TPA was significantly related to the decreased risk number of inpatient visits (IRR: 0.58; 95% CI:0.50-0.67, p < 0.001), inpatient hospital days (IRR: 0.60; 95% CI: 0.42-0.84, p < 0.01), healthcare expenditure (IRR: 0.71; 95% CI: 0.65-0.79, p < 0.001) and catastrophic health expenditures (OR: 0.57; 95% CI: 0.45-0.72, p < 0.001) after adjusting for covariates. CONCLUSIONS: Engaging in moderate-to-vigorous PA may drive a potential decrease in healthcare utilization, healthcare expenditure and household financial risk with a dose-response relationship in China, and some possible policy implications in public health may be considered to promote exercise in the middle-aged and elderly to reduce the medical burden on individuals and healthcare systems.

Clinicopathological characteristics and prognostic factors of elderly small intestine adenocarcinoma using propensity score matching analysis: a study based on SEER database.

BACKGROUND: Small intestine adenocarcinoma (SIA) is a scant disease that has no adequate clinical trials, so its prognostic factors are still unclear, especially in elderly patients. In this article, we aimed to explore the clinicopathology presentation, treatments, outcomes, and predictors of small intestine adenocarcinoma patients aged 65 years or older. METHODS: We retrieved clinicopathology data of small intestine adenocarcinoma patients diagnosed between 2004 and 2015 from the Surveillance Epidemiology and End Results (SEER) database. We clarified patients into two groups: the surgery and the non-surgery group and conducted propensity score matching (PSM) to compare survival outcoming. We identified the prognostic indicators for cancer-specific survival (CSS) and overall survival (OS) by the Cox proportional hazards model. RESULTS: In total, 1018 eligible cases were enrolled, with a median survival of 16 months; the 3-year OS and CSS rates were 36% and 41.7%, and the 5-year OS and CSS rates were 26.5% and 33.3%. Multivariate analyses revealed that age, grade, tumor stage, surgery, and chemotherapy were independent prognostic factors for OS, while grade, tumor stage, surgery, radiation, and chemotherapy were independent factors for CSS. After PSM, only surgery and tumor stage (AJCC 6th) were independent prognostic factors for OS and CSS. CONCLUSION: Surgery could bring benefit to survival for elderly SIA patients, and the early stage of the disease was another significant prognostic factor.

[Molecular mechanism of Wulongdan for improving the learning and memory abilities of rats with chronic cerebral ischemia].

OBJECTIVE: To evaluate the effect of Wulongdan on the learning and memory abilities of rats with chronic cerebral ischemia and explore the mechanisms. METHODS: Male SD Rat models of chronic cerebral ischemia were established by permanent ligation of the bilateral carotid arteries. Three weeks after the operation, the rats were randomly divided into sham-operated group, chronic cerebral ischemia group (model group), high-dose drug group, low-dose drug group and Yinxingye group and received the corresponding treatments on a daily basis for 5 consecutive weeks. Morris water maze was used to assess the learning and memory abilities of the rats, and Western blotting was carried out for detecting the expressions of NR1 and NR2B in the hippocampus and cerebral cortex. RESULTS: Compared with the model group, the rats in high-dose drug, low-dose drug and Yinxingye groups showed significantly shorter time of finding platform in Morris water maze test (P<0.05 or 0.01). The rats in the model group showed significantly lowered expressions of NR1 and NR2B of the cortex and hippocampus than those in the sham-operated group (P<0.01). In comparison with the model group, the high-dose Wulongdan group and Yinxingye group both showed significantly increase expressions of NR1 and NR2B (P<0.01), but their expression levels still remained significantly lower than those in the sham-operated group (P<0.01). CONCLUSION: Wulongdan can enhance the learning and memory abilities of rats with chronic cerebral ischemia, the mechanisms of which may involve increased expressions of NR1 and NR2B in the hippocampus and cortex.

[Effects of Wulongdan on learning and memory abilities of rats with chronic cerebral ischemia].

OBJECTIVE: To evaluate the effect of Wulongdan, a tradition Chinese medicinal preparation, on the learning and memory abilities of rats with chronic cerebral ischemia and explore the mechanisms. METHODS: Male rats with chronic cerebral ischemia induced by permanent ligation of the bilateral carotid arteries were randomized into sham-operated group, chronic cerebral ischemia (model) group, and high-, middle-, and low-dose Wulongdan groups and Yinxingye group. The corresponding treatments were administered in the rats 24 h after the operation once daily for 8 consecutive weeks. Morris water maze and step-through tests were performed after 7 weeks of drug administration. The brain tissues were then taken to observe the morphological changes in the hippocampal neurons with Nissl staining by transmission electron microscopy. RESULTS: Compared with the model group, the latency of finding the platform in Morris water maze test was significantly shortened (P<0.05 or 0.01), and that in step-through test significantly prolonged (P<0.05 or 0.01) in high-, middle-, and low-dose Wulongdan groups and Yinxingye group. In the model group, Nissl staining of the hippocampal CA1 region visualized obvious pathological changes in the neurons, showing a significant difference from the sham-operated and high-dose Wulongdan groups. CONCLUSION: Wulongdan can enhance the learning and memory abilities of rats with chronic cerebral ischemia possibly through a mechanism in relation to neuronal protection in the hippocampus CA1 region.