Background: Immunotherapy can activate the recognition of tumor antigen, build immune memory, and more and more clinical trials have taken the scheme of immunochemotherapy or immunoradiotherapy as a treatment strategy for esophageal squamous cell carcinoma (ESCC). Our objective was to compare the efficacy and safety between pembrolizumab combined with the chemotherapy group and simple chemotherapy in neoadjuvant therapy of ESCC. Methods: Fifty-four ESCC patients with stage II–IVa were enrolled at the Fifth Affiliated Hospital of Sun Yat-sen University between January 2018 and December 2020, including 23 in the pembrolizumab combined with chemotherapy group (combined group), and 31 in the simple chemotherapy group. All patients received radical surgical treatment after two cycles of neoadjuvant therapy. Results: The pathological complete response (pCR) and objective response rate (ORR) in the combined group were significantly higher than that of the simple chemotherapy group (30.4% vs. 9.7%, P=0.048; 86.9% vs. 95.7%, P=0.017) as well as the score of tumor regression ≥2 (80.7% vs. 50.0%, P=0.013). And the complete rate of esophagectomy and R0 /R1 resection rate in the two groups were not statistically significant. Otherwise, the incidence of adverse events in the combined group was similar compared with the simple chemotherapy group. Conclusions: Pembrolizumab combined with chemotherapy showed promising activity with a manageable safety profile. And it could offer a potential new neoadjuvant treatment approach for patients with ESCC.

Findings remain unclear whether neutrophil-to-lymphocyte ratio (NLR) detrimentally affects advanced nasopharyngeal carcinoma (NPC) prognosis. We aim to evaluate the prognostic value of NLR in patients with NPC based on a large-scale cohort from an endemic area. We selected patients retrospectively from a cohort examining long-term cancer outcomes following diagnosis. Neutrophil counts and lymphocyte counts were assessed prior to treatment. Kaplan–Meier method and log-rank test were used to calculate and compare survival outcomes. Additionally, Cox proportional hazards model was utilized to carry out univariate and multivariate analyses. Between October 2009 and August 2012, we enrolled 1550 consecutive NPC patients staged II-IVB. The median value of NLR was 2.27 (interquartile range [IQR], 1.71–3.12). Determined by operating characteristic curve using overall survival (OS) as an endpoint, the cutoff value for NLR was 2.50. At 5 years, NLR > 2.50 was associated with inferior OS (90.3% vs 82.5%; P < 0.001), distant metastasis-free survival (DMFS, 89.4% vs 85.0%; P = 0.014), and progression-free survival (PFS, 80.9% vs 76.5%; P = 0.031) than NLR ≤2.50. In multivariate analysis, NLR was found to be a significant prognostic factor for OS (HR, 1.72; 95% CI, 131–2.24; P < 0.001), DMFS (HR, 1.45; 95% CI, 1.10–1.92; P = 0.009), and PFS (HR, 1.29; 95% CI, 1.04–1.59; P = 0.021). Pretreatment NLR independently affects survival. Our findings suggest that NLR measurements will be of great clinical significance in the management of NPC.

MiR-429 and TLN1 have been shown to affect the biological behaviours of many carcinomas. However, their effects in nasopharyngeal carcinoma (NPC) are not yet clear. Here, we investigated their regulatory relationships and effects on NPC cells. TargetScan was used to predict the regulatory relationships of miR-429 and TLN1 in NPC cells. Then, Western blotting and quantitative real-time PCR (qPCR) were performed to examine TLN1 levels, and qPCR was used to determine miR-429 levels in NPC cell lines with different metastatic characteristics (5-8F, CNE-2, CNE-1, 6-10B and NP69), to investigate whether TLN1 and miR-429 are correlated with the metastatic characteristics of these cells. Next, we upregulated or downregulated miR-429 in 5-8F and 6-10B cells, which have different tumourigenicity and transferability, and examined TLN1 expression by western blotting and qPCR after transfection. QPCR was also performed to confirm successful transfection of miR-429 mimic into 5-8F and 6-10B cells. Dual luciferase reporter gene assay was performed to investigate whether miR-429 regulates TLN1 by binding to its 3′UTR. After transfection, Cell Counting Kit-8 (CCK8) and IncuCyte were used to examine the proliferation of these cells, and wound-healing assay, Transwell migration assay, and invasion assays were performed to investigate the changes in migration and invasion after transfection. Western blotting and qPCR analyses showed that the protein level of TLN1 was negatively correlated with miR-429 in NPC cell lines (P < 0.05), while the mRNA level showed no relation with miR429 expression (P > 0.05). In addition, cells with high transferability showed high TLN1 expression at the protein level, while miR429 expression showed the opposite trend (P < 0.05), but there were no differences at the mRNA level between the different cell lines. Overexpression of miR429 in 5-8F and 6-10B cells was accompanied by downregulation of TLN1 at the protein level (P < 0.05), while there were no significant differences at the mRNA level (P > 0.05). In addition, transferability, proliferation, and invasion were downregulated by miR429 overexpression (P < 0.05). However, dual-luciferase reporter gene assay indicated that TLN1 was not a direct target of miR-429. This study showed that miR-429 functions as a tumour suppressor in NPC by downregulation of TLN1, although the relationship is not direct.

The successful application of photodynamic therapy in the treatment of glioma (CNS WHO grade 4) depends in large part to the effect of killing cells in the infiltrating area after tumor had been removed, when combined with radiotherapy, chemotherapy, and targeted drug therapy. The purpose of this study was to investigate the potential mechanism of TMZ's involvement in the glioma's glycolytic metabolic pathway during photodynamic therapy. The low dose of photodynamic therapy treatment on the cell viability of gliomas was investigated by CCK8. Alterations in reactive oxygen species were detected by flow cytometer. The differentially expressed proteins related to glucose transporter 1 (GLUT-1), matrix metalloproteinase-2 (MMP-2)/actively MMP-2 and apoptosis-associated caspase-3/cleaved caspase-3 were evaluated by Western Blot experiment. Additionally, transmission electron microscopy observed apoptosis, necrosis and the changes of the ultrastructure in U251 cells. In addition, antitumor effects in vivo were tested using orthotopic BALB/c mice with the glioma U87 model. The findings showed that low dose PDT affected mitochondrial function by inducing radical oxygen, hindered cellular glucose transport and metabolism, and induced apoptosis. The results also showed that cell viability considerably decreased and increased cell apoptosis under the PDT therapy. The HIF-1/GLUT-1 axis enhanced the cytotoxicity of temozolomide in gliomas as a result of PDT treatment, which was influenced by ROS. As a result, this study presents PDT as a potential therapeutic approach for treating malignant glioma, and enhanced antitumor effect of TMZ by inhibiting glycolytic pathway.

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [¹⁸F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [¹⁸F]FBTA has a strong STING binding affinity (K_d = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [¹⁸F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG).