Background: Immunotherapy is effective in treating unresectable esophageal squamous cell carcinoma (ESCC), but little is known about its role in the preoperative setting. The aim of this study was to evaluate the safety, feasibility and efficacy of neoadjuvant treatment with camrelizumab plus chemotherapy in locally advanced ESCC.Methods: Patients diagnosed with locally advanced ESCC were retrospectively included if they had received neoadjuvant camrelizumab plus nab-paclitaxel and S1 capsule followed by radical esophagectomy between November, 2019 and June, 2020 at Sun Yat-sen University Cancer Center. Primary endpoints were safety and feasibility. In addition, pathological response and the relationship between tumor immune microenvironment (TIME)/tumor mutational burden (TMB) and treatment response were also investigated.Results: Twelve patients were included and they all received three courses of preoperative treatment with camrelizumab plus nab-paclitaxel/S1. No grade 3 or higher toxicities occurred. No surgical delay or perioperative death was reported. Nine patients (75%) responded to the treatment, four with a complete pathological response (pCR) and five with a major pathological response (MPR). Neither programmed death-ligand 1 (PD-L1) expression nor TMB was correlated with treatment response. TIME analysis revealed that a higher abundance of CD56dim natural killer cells was associated with better pathological response in the primary tumor, while lower density of M2-tumor-associated macrophages was associated with better pathological response in the lymph nodes (LNs).Conclusions: Neoadjuvant camrelizumab plus nab-paclitaxel and S1 is safe, feasible and effective in locally advanced ESCC and is worth further investigation.

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The objective of the current study was to explore the inhibitory effects of quercetin on cadmium-induced autophagy in mouse kidneys. Mice were intraperitoneally injected with cadmium and quercetin once daily for 3 days. The LC3-II/β-actin ratio was used as the autophagy marker, and autophagy was observed by transmission electron microscopy. Oxidative stress was investigated in terms of reactive oxygen species, total antioxidant capacity, and malondialdehyde. Cadmium significantly induced typical autophagosome formation, increased the LC3-II/β-actin ratio, reactive oxygen species level, and malondialdehyde content, and decreased total antioxidant capacity. Interestingly, quercetin markedly decreased the cadmium-induced LC3-II/β-actin ratio, reactive oxygen species levels, and malondialdehyde content, and simultaneously increased total antioxidant capacity. Cadmium can inhibit total antioxidant capacity, produce a large amount of reactive oxygen species, lead to oxidative stress, and promote lipid peroxidation, eventually inducing autophagy in mouse kidneys. Quercetin could inhibit cadmium-induced autophagy via inhibition of oxidative stress. This study may provide a theoretical basis for the treatment of cadmium injury.

As a common phenomenon, chatter is one of the most important factors that inhibit the improvement of productivity and deteriorate the machined surface quality in milling process. In this article, the mathematical model of the dynamic machining process is first constructed with multi-delays, in which the effect of the cutter’s helix angle on the chatter is considered. And a new integral interpolation method is proposed to predict the stability lobes. Based on this method, the mathematical model which is divided into two parts is calculated respectively with an interpolation method and an integration method. Using the Floquet theory, the stability limits of the dynamic milling system for an arbitrary point can thus be precisely predicted. Subsequently, the convergence rate of this integral interpolation method is analyzed. In order to verify the mathematical model, the stability lobes with uniform and variable cutter pitch angle are computed and the results show a good agreement with published experimental data; also one experiment is conducted to validate the proposed model and the method. Simultaneously, the simulation of a stability lobe with non-zero helix angle is also performed and the results validate the fact that the proposed method is capable of predicting stability limits with high accuracy. Finally, the influences of the cutter and process parameters such as helix angle, pitch angle, down-milling or up-milling and radial cutting depth on the milling chatter are analyzed.

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