Background Cancer poses a serious threat to the health of Chinese people, resulting in a major challenge for public health work. Today, people can obtain relevant information from not only medical workers in hospitals, but also the internet in any place in real-time. Search behaviors can reflect a population’s awareness of cancer from a completely new perspective, which could be driven by the underlying cancer epidemiology. However, such Web-retrieved data are not yet well validated or understood. Objective This study aimed to explore whether a correlation exists between the incidence and mortality of cancers and normalized internet search volumes on the big data platform, Baidu. We also assessed whether the distribution of people who searched for specific types of cancer differed by gender. Finally, we determined whether there were regional disparities among people who searched the Web for cancer-related information. Methods Standard Boolean operators were used to choose search terms for each type of cancer. Spearman’s correlation analysis was used to explore correlations among monthly search index values for each cancer type and their monthly incidence and mortality rates. We conducted cointegration analysis between search index data and incidence rates to examine whether a stable equilibrium existed between them. We also conducted cointegration analysis between search index data and mortality data. Results The monthly Baidu index was significantly correlated with cancer incidence rates for 26 of 28 cancers in China (lung cancer: r =.80, P <.001; liver cancer: r =.28, P =.016; stomach cancer: r =.50, P <.001; esophageal cancer: r =.50, P <.001; colorectal cancer: r =.81, P <.001; pancreatic cancer: r =.86, P <.001; breast cancer: r =.56, P <.001; brain and nervous system cancer: r =.63, P <.001; leukemia: r =.75, P <.001; Non-Hodgkin lymphoma: r =.88, P <.001; Hodgkin lymphoma: r =.91, P <.001; cervical cancer: r =.64, P <.001; prostate cancer: r =.67, P <.001; bladder cancer: r =.62, P <.001; gallbladder and biliary tract cancer: r =.88, P <.001; lip and oral cavity cancer: r =.88, ...

BackgroundAdoptive transfer of chimeric antigen receptor (CAR)-modified T cells appears to be a promising immunotherapeutic strategy. CAR combines the specificity of antibody and cytotoxicity of cytotoxic T lymphocytes, enhancing T cells’ ability to specifically target antigens and to effectively kill cancer cells. Recent efforts have been made to integrate the costimulatory signals in the CAR to improve the antitumor efficacy. Epidermal growth factor receptor variant III (EGFRvIII) is an attractive therapeutic target as it frequently expresses in glioma and many other types of cancers. Our current study aimed to investigate the specific and efficient antitumor effect of T cells modified with CAR containing inducible costimulator (ICOS) signaling domain.MethodsA second generation of EGFRvIII/CAR was generated and it contained the EGFRvIII single chain variable fragment, ICOS signaling domain and CD3ζ chain. Lentiviral EGFRvIII/CAR was prepared and human CD3+ T cells were infected by lentivirus encoding EGFRvIII/CAR. The expression of EGFRvIII/CAR on CD3+ T cells was confirmed by flow cytometry and Western blot. The functions of EGFRvIII/CAR+ T cells were evaluated using in vitro and in vivo methods including cytotoxicity assay, cytokine release assay and xenograft tumor mouse model.ResultsChimeric EGFRvIIIscFv-ICOS-CD3ζ (EGFRvIII/CAR) was constructed and lentiviral EGFRvIII/CAR were made to titer of 106 TU/ml. The transduction efficiency of lentiviral EGFRvIII/CAR on T cells reached around 70% and expression of EGFRvIII/CAR protein was verified by immunoblotting as a band of about 57 kDa. Four hour 51Cr release assays demonstrated specific and efficient cytotoxicity of EGFRvIII/CAR+ T cells against EGFRvIII expressing U87 cells. A robust increase in the IFN-γ secretion was detected in the co-culture supernatant of the EGFRvIII/CAR+ T cells and the EGFRvIII expressing U87 cells. Intravenous and intratumor injection of EGFRvIII/CAR+ T cells inhibited the in vivo growth of the EGFRvIII expressing glioma cells.ConclusionsOur study demonstrates that the EGFRvIII/CAR-modified T cells can destroy glioma cells efficiently in an EGFRvIII specific manner and release IFN-γ in an antigen dependent manner. The specific recognition and effective killing activity of the EGFRvIII-directed T cells with ICOS signaling domain lays a foundation for us to employ such approach in future cancer treatment.

The self-assembling MexA-MexB-OprM efflux pump system, encoded by the mexO operon, contributes to facile resistance of Pseudomonas aeruginosa by actively extruding multiple antimicrobials. MexR negatively regulates the mexO operon, comprising two adjacent MexR binding sites, and is as such highly targeted by mutations that confer multidrug resistance (MDR). To understand how MDR mutations impair MexR function, we studied MexR-wt as well as a selected set of MDR single mutants distant from the proposed DNA-binding helix. Although DNA affinity and MexA-MexB-OprM repression were both drastically impaired in the selected MexR-MDR mutants, MexR-wt bound its two binding sites in the mexO with high affinity as a dimer. In the MexR-MDR mutants, secondary structure content and oligomerization properties were very similar to MexR-wt despite their lack of DNA binding. Despite this, the MexR-MDR mutants showed highly varying stabilities compared with MexR-wt, suggesting disturbed critical interdomain contacts, because mutations in the DNA-binding domains affected the stability of the dimer region and vice versa. Furthermore, significant ANS binding to MexR-wt in both free and DNA-bound states, together with increased ANS binding in all studied mutants, suggest that a hydrophobic cavity in the dimer region already shown to be involved in regulatory binding is enlarged by MDR mutations. Taken together, we propose that the biophysical MexR properties that are targeted by MDR mutations-stability, domain interactions, and internal hydrophobic surfaces-are also critical for the regulation of MexR DNA binding.

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A survey of the clinical data on acute myeloid leukemia (AML) over the past 10 years in the treatment center of Children's Hospital was presented. The aim of the study was to identify the factors influencing the treatment abandonment rate (AR) of AML. Of the 474 AML cases examined, 264 were abandoned (55.7%). The most important factor affecting AR appeared to be the AML subtype-that is, the M3 versus non-M3 (42% vs. 60%). Patient age was observed to be closely related to AR-the older the patients, the lower the AR-and infants had the highest prevalence of abandonment (84.2%). The patient's residential location was markedly correlated to AR, which was almost inversely proportional to the size of the township where the patient came from. From large cities, intermediate and small towns to countryside villages, the AR increased linearly. So was the correlation with health insurance coverage, which decreased in the same way. Sex and karyotypes did not affect AR. In conclusion, the patients' financial burden and the perceived incurability of AML were the 2 leading factors dominating the decision for abandonment in parents and caregivers.