Efficacy, safety, and survival of neoadjuvant immunochemotherapy in operable non-small cell lung cancer: a systematic review and meta-analysis

BackgroundNeoadjuvant immunochemotherapy may benefit patients with non-small cell lung cancer (NSCLC), but its impact requires further investigation.MethodsA meta-analysis was conducted. PubMed, Embase, Web of Science, and the Cochrane Library were searched. The study was registered in PROSPERO (registration no. CRD42022360893).Results60 studies of 3,632 patients were included. Comparing with neoadjuvant chemotherapy, neoadjuvant immunochemotherapy showed higher pCR (RR: 4.71, 95% CI: 3.69, 6.02), MPR (RR, 3.20, 95% CI: 2.75, 3.74), and ORR (RR, 1.46, 95% CI: 1.21, 1.77), fewer surgical complications (RR: 0.67, 95%CI: 0.48, 0.94), higher R0 resection rate (RR: 1.06, 95%CI: 1.03, 1.10, I2 = 52%), and longer 1-year and 2-year OS, without affecting TRAEs. For neoadjuvant immunochemotherapy in NSCLC, the pooled pCR rate was 0.35 (95% CI: 0.31, 0.39), MPR was 0.59 (95% CI: 0.54, 0.63), and ORR was 0.71 (95% CI: 0.66, 0.76). The pooled incidence of all grade TRAEs was 0.70 (95% CI: 0.60, 0.81), and that of >= grade 3 TRAEs was 0.24 (95% CI: 0.16, 0.32). The surgical complications rate was 0.13 (95% CI: 0.07, 0.18) and R0 resection rate was 0.98 (95% CI: 0.96, 0.99). The pooled 1-year OS was 0.97 (95%CI: 0.96, 0.99), and 2-year OS was 0.89 (95%CI: 0.83, 0.94). Patients with squamous cell carcinoma, stage III or higher PD-L1 performed better. Notably, no significant differences were observed in pCR, MPR, and ORR between 2 or more treatment cycles. Pembrolizumab-, or toripalimab-based neoadjuvant immunochemotherapy demonstrated superior efficacy and tolerable toxicity.ConclusionAccording to our analysis, reliable efficacy, safety, and survival of neoadjuvant immunochemotherapy for operable NSCLC were demonstrated.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022360893, identifier CRD42022360893

The impact of political connections on corporate tax burden: evidence from the Chinese market

This paper investigates how political connections affect corporate tax burden. We construct two multi-tiered political connections series and employ the Propensity Score Matching approach. We find that stronger political connections lead to a lower corporate tax burden in Chinese listed firms. Specifically, the nominal (effective) tax rate decreases by an average of 1.03% (0.33%) as the hierarchical position of Chairman or CEO in the government rises by one rank (e.g., from a sub-provincial to provincial minister), and by an average of 0.99% (0.98%) as the administrative level of the government where the Chairman or CEO holds the position rises by one level (e.g., from a provincial to a central government). Our further analysis shows that political connections reduce the tax burden for both SOEs and non-SOEs, especially for the latter

Ionizing Radiation-Induced Cellular Senescence in Normal, Non-transformed Cells and the Involved DNA Damage Response: A Mini Review

Cellular senescence is identified by a living cell in irreversible and persistent cell cycle arrest in response to various cellular stresses. Senescent cells secrete senescence-associated secretory phenotype factors that can amplify cellular senescence and alter the microenvironments. Radiotherapy, via ionizing radiation, serves as an effective treatment for local tumor control with side effects on normal cells, which can induce inflammation and fibrosis in irradiated and nearby regions. Research has revealed that senescent phenotype is observable in irradiated organs. This process starts with DNA damage mediated by radiation, after which a G2 arrest occurs in virtually all eukaryotic cells and a mitotic bypass is possibly necessary to ultimately establish cellular senescence. Within this complex DNA damage response signaling network, ataxia telangiectasia-mutated protein, p53, and p21 stand out as the crucial mediators. Senolytic agents, a class of small molecules that can selectively kill senescent cells, hold great potential to substantially reduce the side effects caused by radiotherapy while reasonably steer clear of carcinogenesis

Salmonella effector SopF regulates PANoptosis of intestinal epithelial cells to aggravate systemic infection

ABSTRACTSopF, a newly discovered effector secreted by Salmonella pathogenicity island-1 type III secretion system (T3SS1), was reported to target phosphoinositide on host cell membrane and aggravate systemic infection, while its functional relevance and underlying mechanisms have yet to be elucidated. PANoptosis (pyroptosis, apoptosis, and necroptosis) of intestinal epithelial cells (IECs) has been characterized as a pivotal host defense to limit the dissemination of foodborne pathogens, whereas the effect of SopF on IECs PANoptosis induced by Salmonella is rather limited. Here, we show that SopF can attenuate intestinal inflammation and suppress IECs expulsion to promote bacterial dissemination in mice infected with Salmonella enterica serovar Typhimurium (S. Typhimurium). We revealed that SopF could activate phosphoinositide-dependent protein kinase-1 (PDK1) to phosphorylate p90 ribosomal S6 kinase (RSK) which down-regulated Caspase-8 activation. Caspase-8 inactivated by SopF resulted in inhibition of pyroptosis and apoptosis, but promotion of necroptosis. The administration of both AR-12 (PDK1 inhibitor) and BI-D1870 (RSK inhibitor) potentially overcame Caspase-8 blockade and subverted PANoptosis challenged by SopF. Collectively, these findings demonstrate that this virulence strategy elicited by SopF aggregates systemic infection via modulating IEC PANoptosis through PDK1-RSK signaling, which throws light on novel functions of bacterial effectors, as well as a mechanism employed by pathogens to counteract host immune defense