Clinical Efficacy of Immune Checkpoint Inhibitors in Older Non-small-Cell Lung Cancer Patients: A Meta-Analysis.

Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape among non-small-cell lung cancer (NSCLC) patients. The efficacy of ICI therapy in older patients (≥65 years) is controversial and not fully clarified. We performed a systematic review and meta-analysis to evaluate the efficacy of ICIs in patients with advanced or metastatic NSCLC based on age (<65 years vs. ≥65 years). Methods: A comprehensive literature search for eligible randomized control phase II/III trials that compared the efficacy of anti-PD-1/PD-L1 agents against chemotherapy in advanced or metastatic NSCLC patients. Pooled overall survival (OS) and progression-free survival (PFS) estimates were calculated based on random/fixed effects models according to the heterogeneity between the studies. Results: A total of 10 studies involving 8 randomized controlled trials (2 updates) were enrolled in this meta-analysis [2,662 young patients (<65 years) and 1,971 older patients (≥65 years)]. The efficacy of anti-PD-1/PD-L1 agents is comparable between young (<65 years) and older (≥65 years) patients for OS [HR 0.75 95% CI (0.64-0.88) vs. 0.76 95% CI (0.66-0.87)]. However, our pooled analysis was not sufficient to show a significant benefit in terms of PFS for anti-PD-1/PD-L1 agents [HR 0.87 95% CI (0.74-1.01), P = 0.06]. In addition, we failed to see a PFS superiority of anti-PD-1/PD-L1 agents against chemotherapy in two age subgroups [<65 years and ≥65 years, HR 0.85 95% CI (0.72-1.01), P = 0.07 and HR 0.87 95% CI (0.68-1.10), P = 0.25]. Conclusion: ICIs therapy presents comparable efficacy in older advanced or metastatic NSCLC patients with young patients.

Dark tea extracts: Chemical constituents and modulatory effect on gastrointestinal function.

Processing of dark tea varieties, such as Fu brick tea, Liupao tea, Qianliang tea, and Qing brick tea, includes solid-state fermentation involving microorganisms. In this study, we analyzed the major chemical constituents of dark tea extracts and evaluated their modulatory effect on the gastrointestinal function in normal mice, including the improvement of gastrointestinal transit and intestinal microbial, as well as the attenuation of intestinal microbial dysbiosis and intestinal pathological damage, and the adjustment of immune function in antibiotic-treated mice. Substantial differences in major chemical constituents, including total polyphenols, total organic acids, water extract content, 18 free amino acids, gallic acid, and six tea catechins, were observed among Fu brick tea, Qianliang tea, Qing brick tea, and Liupao tea extracts. Extracts from the four dark tea varieties significantly promoted gastrointestinal transit and colonization of beneficial Bifidobacterium and Lactobacillus, and inhibited the growth of harmful Escherichia coli and Enterococcus in normal mice. In addition, Qianliang tea, Qing brick tea, and Liupao tea extracts significantly accelerated the reversal of the ampicillin sodium-induced pathological damage in the ileum, intestinal bacterial dysbiosis (Bifidobacterium, Lactobacillus, E. coli, and Enterococcus), and low immunity.

TREM2 inhibits inflammatory responses in mouse microglia by suppressing the PI3K/NF-κB signaling.

This study aimed to investigate the effects of triggering receptor expressed on myeloid cell-2 (TREM2) on the production of pro-inflammatory mediators and cytokines induced by lipopolysaccharide (LPS) in BV2 microglia. TREM2 expression or TREM2-specific siRNA were used to induce TREM2 overexpression or silencing. The BV2 cells were pre-treated with the PI3 K inhibitor of LY294002 for 1 h and stimulated with LPS for 24 h. Then, the cell viability, apoptosis, phagocytosis, nitric oxide (NO), lactate dehydrogenase (LDH), and cytokine production, as well as the activation of AKT and NF-kB were determined, respectively. We found LPS stimulation significantly reduced BV2 cell viability, enhanced BV2 cell phagocytosis and apoptosis compared to the control groups. In addition, LPS stimulation significantly increased the production of NO, LDH, TNF-α, IL-1ß, and the activation of AKT and NF-kB, while decreased the levels of IL-10 and TGF-ß1. However, these pro-inflammatory effects were significantly attenuated by TREM2 overexpression or pre-treatment with LY294002, while enhanced by TREM2 silencing. Thus, we concluded that TREM2 inhibited neuroinflammation by down-regulating PI3 K/AKT and NF-kB signaling in BV2 microglia. Above all, therapeutic enhanced TREM2 expression may be a new strategy for intervention of neuroinflammatory diseases.

Polymorphisms of VEGFA gene and susceptibility to hemorrhage risk of brain arteriovenous malformations in a Chinese population.

AIM: To evaluate the influence of the vascular endothelial growth factor A (VEGFA) polymorphisms on risk of presentation with intracerebral hemorrhage (ICH). METHODS: Nine selected VEGFA single-nucleotide polymorphisms (SNPs) were genotyped in 311 patients with brain arteriovenous malformations (BAVM) in a Chinese population. Associations between individual SNPs/haplotypes and the hemorrhage risk of BAVMs were evaluated using logistic regression analysis. RESULTS: In the single-locus analysis, rs1547651 was associated with increased risk of ICH (adjusted OR=2.11, 95% CI=1.01-4.42 compared with the AA genotype). In particular, an increased risk for ICH was associated with this variant in female patients (adjusted OR=3.21, and 95% CI=0.99-10.36). Haplotype-based analyses revealed that haplotype 'GC' in block 1 and haplotype 'ACC' in block 2 were associated with a 30%-38% reduction in the risk of ICH in patients with BAVMs compared to the most common haplotype (P(sim)=0.033 and P(sim)=0.005, respectively). The protective effect of haplotype 'ACC' in block 2 was more evident in male patients and subjects with BAVMs of a size ≥3 cm (adjusted OR=0.57, 95% CI=0.34-0.97 and adjusted OR=0.57, 95% CI=0.31-0.86, respectively). CONCLUSION: The results suggest that VEGFA gene variants may contribute to ICH risk of BAVM.

Survey of attitudes and behaviors of healthcare professionals on delirium in ICU.

OBJECTIVE: To assess the medical community's awareness and practice regarding delirium in the intensive care unit (ICU). METHODS: One hundred and ten predesigned questionnaires were distributed to ICU practitioners in the affiliated hospitals of Zhejiang University. RESULTS: A total of 105 valid questionnaires were collected. Totally, 55.3% of the clinicians considered that delirium was common in the ICU. Delirium was believed to be a significant or serious problem by 70.5% of respondents, and under-diagnosis was acknowledged by 56.2% of the respondents. The incidence of ICU delirium is even more under-estimated by the pediatric doctors compared with their counterparts in adult ICU (P less than 0.05). Primary disease of the brain (agreed by 82.1% of the respondents) was believed to be the most common risk factor for delirium. None of the ICU professionals screened delirium or used a specific tool for delirium assessment routinely. The vast majority (92.4%) of respondents had little knowledge on the diagnosis and the standard treatment of delirium. CONCLUSIONS: Although delirium is considered as a serious problem by a majority of the surveyed ICU professionals, it is still under-recognized in routine critical care practice. Data from this survey show a disconnection between the perceived significance of delirium and the current practices of monitoring and treatment in ICU in China.

Describing Chinese hospital activity with diagnosis related groups (DRGs). A case study in Chengdu.

OBJECTIVE: To examine the applicability of an Australian casemix classification system to the description of Chinese hospital activity. DESIGN: A total of 161,478 inpatient episodes from three Chengdu hospitals with demographic, diagnosis, procedure and billing data for the year 1998/1999, 1999/2000 and 2000/2001 were grouped using the Australian refined-diagnosis related groups (AR-DRGs) (version 4.0) grouper. MAIN OUTCOME MEASURES: Reduction in variance (R2) and coefficient of variation (CV). RESULTS: Untrimmed reduction in variance (R2) was 0.12 and 0.17 for length of stay (LOS) and cost respectively. After trimming, R2 values were 0.45 and 0.59 for length of stay and cost respectively. CONCLUSIONS: The Australian refined DRGs provide a good basis for developing a Chinese grouper.