RESUMO
Background: Immune checkpoint inhibitors (ICIs) play an important role in the treatment of esophageal cancer (EC). However, their efficacy is variable, and there are still no effective and convenient biomarkers to identify and assess their efficacy. In recent years, programmed cell death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB) and other commonly used biomarkers still cannot meet clinical needs. PNI is easy to obtain and its predictive value for the prognosis of immunotherapy has been confirmed in many cancer species, but the relationship between PNI and the efficacy of immunotherapy for esophageal cancer is still unclear. Therefore, this study aims to explore the predictive value of PNI in advanced esophageal cancer treated with ICIs. Methods: The clinicopathological features of 78 patients with advanced EC who received immunotherapy in the 900th Hospital of the Joint Logistics Team from September 2018 to May 2022 were retrospectively analyzed. The laboratory test results within 10 days prior to the start of ICI treatment were recorded, including absolute lymphocyte count and albumin (ALB) level. Meanwhile, the effects of pre-treatment prognostic nutritional index (PNI) and body mass index (BMI) on the overall survival (OS) and progression-free survival (PFS) in patients with advanced EC were analyzed. Results: The median age of the enrolled patients was 58 years, and 38 patients (48.7%) received second-or-later-line therapy. The median progression-free survival (mPFS) and median overall survival (mOS) were 7.4 months and 13 months, respectively. The mPFS and mOS were 8.8 months and 15 months, respectively, in the high baseline PNI subgroup, which were significantly higher than those in the low baseline PNI subgroup (4.7 and 8.2 months, respectively; both P<0.05). Multivariate regression analysis showed that low baseline PNI was an independent predictor of poor PFS [hazard studio (HR) =0.35, 95% CI: 0.14-0.85, P=0.020) and poor OS (HR =0.41, 95% CI: 0.17-0.99, P=0.047) and treatment line was an independent predictor of PFS. Baseline BMI was not significantly associated with prognosis. Conclusions: PNI is a simple and effective biomarker for predicting the prognosis of immunotherapy in patients with advanced EC, although further prospective studies are warranted.
RESUMO
The enrichment of zinc oxide nanoparticles (ZnO NPs) in waste activated sludge (WAS) has raised concerns about their potential impact on anaerobic digestion of WAS. To date, there is no information regarding how to attenuate the negative effects of ZnO NPs on WAS anaerobic digestion. In this study, it was found that the appropriate amount of cationic polyacrylamide (cPAM) could mitigate the toxicity of ZnO NPs. During short-term exposure, the supplement of 4.0 mg cPAM/g TSS significantly restored biochemical methane potential from 28.6% inhibition to 9.3% inhibition compared with the control digester (P < 0.01). The spiked cPAM promoted the solubilization and acidification stages by weakening the contact between ZnO NPs and anaerobes in anaerobic digestion process, thus providing abundant substance for sequent bio-utilization. In the long-term semi-continues operated reactor, the continuous replacement of cPAM (at 4.0 mg/g TSS) significantly strengthened the recovery of VS destruction rate (20.3% to 26.4%, P < 0.01) and the daily yield of methane (93.5 mL/d to 124.2 mL/d, P < 0.01). Consistent with the restored performance, the application of cPAM increased the total microbial communities and the relative abundances of dominant acidogens and methanogens. Further explorations showed decreased toxicity of ZnO NPs primarily attributed to the decline of reactive oxygen species (ROS) induced by ZnO NPs.