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As a typical tumor microenvironment-responsive therapy, chemodynamic therapy (CDT), producing hydroxyl radicals ( • OH) to eliminate tumor cells, has demonstrated great promise. Nevertheless, there are still major challenges: • OH generated from endogenous H 2 O 2 is usually insufficient; the CDT effect is strongly dependent on the pre-reaction with glutathione. Addressing the challenges, Au@MnSe 2 core-shell nanoagent for synergetic chemodynamic-photothermo-photocatalytic therapy combined with tetramodal imaging, including magnetic resonance imaging, computed tomography, photoacoustic, and infrared thermal imaging is reported. Distinct from the reported glutathione-depleting agents, Mn 2+ in MnSe 2 allows immediate generation of • OH, independent of pre-reaction. Meanwhile, Mn 3+ consumes glutathione by its conversion to Mn 2+ . The Au-MnSe 2 combination promotes photothermal conversion and photocatalytic reaction, resulting in largely enhanced • OH generation from endogenous H 2 O 2 and significant hyperthermia. Meanwhile, immune response is effectively activated: the intratumoral expression of programmed cell death-1 and proinflammatory cytokines increase to 4-7 folds; the cytotoxic and helper T lymphocytes cells in the tumor area increase to more than 2.5-folds; an evident, temporary systemic immunostimulatory effect is demonstrated. High tumor inhibition rate (≈97.3%) and greatly prolonged survival are obtained. This highly-integrated design coordinating three different therapies with four different imaging modals provide new possibilities for high-performance theranostic nanoagents., (© 2022 Wiley-VCH GmbH.)

Objectives: Genetic mutation is one of the important causes for tumor genesis and development, but genetic mutation in nasopharyngeal carcinoma (NPC) has rarely been reported. This study explored the role of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR), and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in the efficacy and prognosis in patients with NPC., Methods: A total of 31 patients with advanced NPC, who came from the Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University/Hunan Provincial Cancer Hospital, were enrolled. All of the exons of 288 genes, introns of 38 genes and promoters or fusion breakpoint regions from the nasopharyngeal biopsy tissues before treatment were detected by the gene sequencing platform Illumina NextSeq CN500. The coding regions of 728 genes were carried out a high-depth sequencing of target region capture, and the 4 variant types of tumor genes (including point mutations, insertion deletions of small fragments, copy number variations, and currently known fusion genes) were detected. All of 31 patients received platinum-based induction chemotherapy combined with concurrent chemoradiotherapy and were followed up for a long time., Results: The 3-year regional failure-free survival (RFFS) and disease-free survival (DFS) in patients with PI3K-Akt pathway mutation were significantly lower than those in unmutated patients (χ 2 =6.647, P <0.05). The 3-year RFFS and DFS in patients with mTOR pathway mutations were significantly lower than those in unmutated patients, and there was significant difference (χ 2 =5.570, P <0.05). The rate of complete response (CR) in patients with unmutated AMPK pathway was significantly higher than that in patients with mutation at 3 months after treatment ( P <0.05), and the 3-year RFFS and DFS in patients with AMPK pathway mutation were significantly lower than those in unmutated patients (χ 2 =4.553, P <0.05). PI3K-Akt/mTOR/AMPK signaling pathway mutations and pre-treatment EB virus DNA copy numbers were independent prognostic factors for 3-year RFFS and DFS in patients with NPC (both P <0.05)., Conclusions: The NPC patients with PI3K-Akt/mTOR/AMPK signaling pathway mutation have poor prognosis, and the detection of PI3K-Akt, mTOR, AMPK driver genes and signaling pathways by next-generation sequencing is expected to provide new idea for basic research and targeted therapy of NPC.

Nanozyme-based colorimetry was suggested to be a rapid method for biomarker (e.g. glutathione) detection, but this method suffers from lack of efficiency and low-toxicity nanozymes till now. Herein, quantum dots of TiO2 loaded on carbon (TiO2/C-QDs) oxidase-like nanozymes were prepared via a hydrothermal treatment of tiny and few-layered Ti3C2Tx MXene nanosheets, which possess abundant thermodynamic metastable Ti atoms on MXene margins as raw materials for the preparation of TiO2/C-QDs. The oxygen vacancy in TiO2 on the surface of the carbon matrix can facilitate O2 adsorption in the solution and generate reactive oxygen species (ROS), thereby quickly oxidizing 3,3',5,5'-tetramethylbenzidine (TMB) to its oxidized form (TMBox) in the absence of H2O2. After adding glutathione (GSH), TMBox was able to be restored to TMB, which resulted in a corresponding decrease in the UV-vis absorbance value at 652 nm. Furthermore, this assay possesses good selectivity, excellent specificity and high sensitivity (limit of detection: 0.2 μM), which made it possible to efficiently detect GSH in complex biological samples such as human serum.

It is known that hypertension could increase the plasma levels of VEGF and that β-blockers propranolol could counteract the effect. Our aim was to explore the possibility of improving survival outcomes for patients with and patients without hypertension. In addition, we also compared the efficacy of the usage of β-blockers in inoperable non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed 1753 NSCLC patients who underwent concurrence/sequential chemoradiotherapy in our hospital from 1994 to 2005. A total of 606 inoperable patients with stage III were enrolled in this study. Fifty-five patients survived until the follow-up date of May 2011. From the 606 patients, 123 of them had hypertension. We identified 11 of them who took β-blockers orally. Kaplan-Meier methods and Cox proportional hazard model were utilized to analyze the overall survival (OS) outcome among patients with hypertension and patients without hypertension. After that, we compared the patients who took β-blockers with patients who did not take β-blockers in the whole stage III cohort using the same approaches. The Kaplan-Meier analysis revealed that there were no significant survival outcomes between hypertension and non-hypertention groups (P>0.05). No significant difference was found between using β-blockers and not using them in the hypertention group (P>0.05). We also found no statistical significance between using β-blockers and not using them in the whole cohort of 606 NSCLC patients (P>0.05). The results from both univariate or multivariate analysis using the Cox proportional hazards regression model indicated that there was no statistical difference between hypertension and non-hypertension group. There was also no difference between using β-blockers and not using them in the whole stage III cohort (P>0.05). For the patients with hypertension, the usage of β-blockers did not influence the overall survival in stage III inoperable NSCLC. Further randomized clinical trials will be warranted to validate this finding., Competing Interests: None.