Comprehensive identification of somatic structural variations (SVs) and understanding their mutational mechanisms in cancer might contribute to understanding biological differences and help to identify new therapeutic targets. Unfortunately, characterization of complex SVs across the whole genome and the mutational mechanisms underlying esophageal squamous cell carcinoma (ESCC) is largely unclear. To define a comprehensive catalog of somatic SVs, affected target genes, and their underlying mechanisms in ESCC, we re-analyzed whole-genome sequencing (WGS) data from 31 ESCCs using Meerkat algorithm to predict somatic SVs and Patchwork to determine copy-number changes. We found deletions and translocations with NHEJ and alt-EJ signature as the dominant SV types, and 16% of deletions were complex deletions. SVs frequently led to disruption of cancer-associated genes (e.g., CDKN2A and NOTCH1) with different mutational mechanisms. Moreover, chromothripsis, kataegis, and breakage-fusion-bridge (BFB) were identified as contributing to locally mis-arranged chromosomes that occurred in 55% of ESCCs. These genomic catastrophes led to amplification of oncogene through chromothripsis-derived double-minute chromosome formation (e.g., FGFR1 and LETM2) or BFB-affected chromosomes (e.g., CCND1, EGFR, ERBB2, MMPs, and MYC), with approximately 30% of ESCCs harboring BFB-derived CCND1 amplification. Furthermore, analyses of copy-number alterations reveal high frequency of whole-genome duplication (WGD) and recurrent focal amplification of CDCA7 that might act as a potential oncogene in ESCC. Our findings reveal molecular defects such as chromothripsis and BFB in malignant transformation of ESCCs and demonstrate diverse models of SVs-derived target genes in ESCCs. These genome-wide SV profiles and their underlying mechanisms provide preventive, diagnostic, and therapeutic implications for ESCCs.

In our work, we have successfully synthesized WO 3 nanosheets via a simple, fast, and organic additives-free hydrothermal method. The obtained products are 200−500 nm-sized with square corners and high crystallinity. A possible formation mechanism of WO 3 nanosheets is discussed in this study based on the experimental results and our understanding. WO 3 nanosheets modified with Pt exhibit enhanced photocatalytic activity of tetracycline compared with bare WO 3 nanosheets under visible-light irradiation (λ > 420 nm). Furthermore, the effects of Pt as cocatalyst can be clearly drawn, and the degradation ratio of 2% Pt/WO 3 nanosheets is over 3 times that of bare WO 3 nanosheets, which is reasonable to expect the obvious Ptdependent activity. The addition of 10 mL of iso-propanol leads to a considerable decreased degradation ratio (DR) of tetracycline (TC) on 2% Pt/WO 3 photocatalysts, further indicating the •OH radicals do exist in the process of the photocatalytic oxidation (PCO) of TC.

Background: Globally, the increasingly severe population ageing issue has been creating challenges in terms of medical resource allocation and public health policies. The aim of this study is to address the space-time trends of the population-ageing rate (PAR), the number of medical resources per thousand residents (NMRTR) in mainland China in the past 10 years, and to investigate the spatial and temporal matching between the PAR and NMRTR in mainland China. Methods: The Bayesian space-time hierarchy model was employed to investigate the spatiotemporal variation of PAR and NMRTR in mainland China over the past 10 years. Subsequently, a Bayesian Geo-Detector model was developed to evaluate the spatial and temporal matching levels between PAR and NMRTR at national level. The matching odds ratio (OR) index proposed in this paper was applied to measure the matching levels between the two terms in each provincial area. Results: The Chinese spatial and temporal matching q-statistic values between the PAR and three vital types of NMRTR were all less than 0.45. Only the spatial matching Bayesian q-statistic values between the PAR and the number of beds in hospital reached 0.42 (95% credible interval: 0.37, 0.48) nationwide. Chongqing and Guizhou located in southwest China had the highest spatial and temporal matching ORs, respectively, between the PAR and the three types of NMRTR. The spatial pattern of the spatial and temporal matching ORs between the PAR and NMRTR in mainland China exhibited distinct geographical features, but the geographical structure of the spatial matching differed from that of the temporal matching between the PAR and NMRTR. Conclusion: The spatial and temporal matching degrees between the PAR and NMRTR in mainland China were generally very low. The provincial regions with high PAR largely experienced relatively low spatial matching levels between the PAR and NMRTR, and vice versa. The geographical pattern of the temporal matching between the PAR and NMRTR exhibited the feature of north-south differentiation.

Background In the era of precision medicine, chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations. How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring. This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy (HCT) for advanced patients with non-small cell lung cancer (NSCLC), especially those with malignant pleural effusion. Methods We retrospectively evaluated medical records of 93 patients with advanced NSCLC (stage IIIB-IV) from March 2011 to January 2014. The patients were divided into HCT and chemotherapy (CT) groups. The HCT group was treated with gemcitabine and cisplatin (GP) regimen combined with regional radiofrequency deep hyperthermia, while the CT group was treated with GP regimen only. Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not. Clinical treatment results and adverse reactions were compared and analyzed after treatment. SPSS 19.0 software (SPSS Inc., USA) was used for statistical data processing. P values less than 0.05 were accepted to be statistically significant. Results Among the 93 patients, HCT group included 48 patients (16 patients with malignant pleural effusion), CT group included 45 patients (10 patients with malignant pleural effusion). There was no significant difference between the two groups in patient characteristics. The overall response rate (ORR) of pleural effusions was much better in HCT group than that in CT group (81.2% vs . 40.0%, P = 0.046). The patients in HCT group had lower incidence rate of weakness (12.5% vs . 46.7%, χ 2 = 13.16, P < 0.001) and gastrointestinal (25.0% vs . 77.8%, χ 2 = 25.88, P < 0.001) adverse reactions than that in CT group. The objective tumor response and survival showed no significant differences. Conclusions Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients. Also, it could greatly reduce the chemotherapy toxic effects in the incidence of weakness and gastrointestinal adverse reactions in advanced NSCLC patients.