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Abstract Background In China, stomach cancer is the third most common cancer and the third leading cause of cancer death. Few studies have examined Chinese stomach cancer patients’ medical expenses and their associated trends. The Cancer Screening Program in Urban China (CanSPUC) is a Major Public Health Project funded by the central government. Through this project, we have extracted patients’ medical expenses from hospital billing data to examine the costs of the first course treatments (which refers to 2 months before and 10 months after the date of cancer diagnosis) in Chinese patients with stomach cancer and the associated trends. Methods The expense data of 14,692 urban Chinese patients with stomach cancer were collected from 40 hospitals in 13 provinces. We estimated the inflation-adjusted medical expenses per patient during 2002–2011. We described the time trends of medical expenses at the country-level, and those trends by subgroup, and analyzed the compositions of medical expenses. We constructed the Generalized Linear Mixed (GLM) regression model with Poisson distribution to examine the factors that were associated with medical expenses per patient. Results The average medical expenses of the first course treatments were about 43,249 CNY (6851 USD) in 2011, more than twice of that in 2002. The expenses increased by an average annual rate of 7.4%. Longer stay during hospitalization and an increased number of episodes of care are the two main contributors to the expense increase. The upward trend of medical expenses was observed in almost all patient subgroups. Drug expenses accounted for over half of the medical expenses. Conclusions The average medical expenses of the first course (2 months before and 10 months after the date of cancer diagnosis) treatments per stomach cancer patient in urban China in 2011 were doubled during the previous 10 years, and about twice as high as the per capita disposable income of urban households in the same year. Such high expenses indicate that it makes economic sense to invest in cancer prevention and control in China.

Most defensins are cationic antimicrobial peptides with broad-spectrum killing activity against bacteria, fungi and enveloped viruses. However, it should be recognized that there are some non-cationic β-defensins in organisms, which need to be further studied. In this study, a new spliced isoform of anionic β-defensin from flounder (Paralichthys olivaceus, fBD) was identified, and its antibiosis, chemotaxis and modulation of phagocytosis were examined. In addition, the contributions of fBD to the antimicrobial activity of extracellular traps (ETs) were also analyzed. The recombinant fBD (rfBD) could effectively inhibit the growth of Gram-positive bacteria (S. aureus, Micrococcus luteus) and Gram-negative bacteria (E. coli, V. alginolyticus, V. anguillarum). An indirect immunofluorescence assay showed that the fBD was co-localized in the extracellular traps released by the leukocytes. When the ETs were blocked with antibodies against rfBD, the proliferation of S. aureus and E. coli incubated with ETs tended to increase compared with that in the control group. In addition, the results obtained by flow cytometry showed that the rfBD could significantly chemoattract leukocytes and increase phagocytic activity in vitro. In conclusion, this study provides new insights into the biological function of anionic defensins, which can serve as one of the important effectors in extracellular traps and as a bridge between innate and adaptive immunity in teleosts.

In this paper, we propose a novel two-degree-of-freedom (TDOF) nonlinear energy harvester without internal resonance to realize broadband harvesting characteristic. To show the performance, a TDOF nonlinear electromagnetic harvester is designed. The electromechanical coupling system is established and solved by adopting the harmonic balance method. The modulation equations are constructed, the first-order harmonic solutions of the system are obtained and the frequency response curves of the displacement and current are plotted. The advantage of the proposed harvester is compared to the conventional single-degree-of-freedom (SDOF) nonlinear model and the corresponding TDOF linear system, the results achieve that the proposed scheme can enhance the bandwidth of the harvesting energy. Furthermore, the influences of system parameters on the response are discussed. The accuracy of the first-order harmonic results is revealed by numerical simulations. To further demonstrate the accuracy of analytical solutions, the finite element simulation is constructed in ANSYS finite element analysis (FEA) software. The performance predictions from the analytical solutions are compared with results from FEA. It is convincingly demonstrated that periodic solutions have a degree of good consistency for the behavior of frequency response curves. [ABSTRACT FROM AUTHOR]

Abstract Background Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. Methods From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY = 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. Results A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage I, 39,302 CNY for stage II, 40,353 CNY for stage III, and 37,432 CNY for stage IV diseases (P

Abstract Background Hirame rhabdovirus virus (HIRRV) is a rhabdovirus that causes acute hemorrhage disease in fish culture, resulting in a great economic loss in parts of Asia and Europe. Methods In this study, we isolated a virus strain named as CNPo2015 from cultured Japanese flounder in Shandong province, China. Cell isolation, electron microscopic observation, RT-PCR detection and phylogenetic analysis were used for virus identification. Further, artificial infection experiment was conducted for virulence testing. Results The gross signs included abdominal distension, fin reddening and yellow ascitic fluid in the abdominal cavity. Histopathological examination revealed marked cell degeneration and necrosis in the kidney. The tissue homogenates induced obvious cytopathic effects in EPC, FHM and FG cell lines. Electron microscopic observation showed the virus had a bullet-like shape with a capsule membrane. RT-PCR and sequencing analysis revealed that CNPo2015 belonged to the HIRRV with high sequence identity to HIRRV isolates. Infection experiment confirmed that the HIRRV CNPo2015 strain was virulent to flounder juveniles with a LD50 value of 1.0 × 105.9 TCID50/fish. Conclusion In conclusion, we described the first isolation and characterization of a HIRRV from Japanese flounder in China. This will provide a candidate material for further research on the infection mechanism and preventive strategies of HIRRV.

B cells have recently been proven to have phagocytic activities, but few studies have explored the relevant regulation mechanisms. In this study, we showed that the Japanese flounder (Paralichthys olivaceus) membrane-bound (m)IgM+ B lymphocyte population could phagocytose inactivated Lactococcus lactis with a mean phagocytic rate of 25%. High-purity mIgM+ B lymphocytes were subsequently sorted to investigate the cellular response to L. lactis stimulation in vitro. Transcriptome analysis identified 1,375 differentially expressed genes (DEGs) after L. lactis stimulation, including 975 upregulated and 400 downregulated genes. Many of these DEGs were enriched in multiple pathways associated with phagocytosis such as focal adhesion, the phagosome, and actin cytoskeleton regulation. Moreover, many genes involved in phagolysosomal function and antigen presentation were also upregulated after stimulation, indicating that mIgM+ B lymphocytes may degrade the internalized bacteria and present processed antigenic peptides to other immune cells. Interestingly, the type I interferon 3 (IFN I-3) gene was upregulated after L. lactis stimulation, and further analysis showed that the recombinant (r)IFN I-3 significantly enhanced phagocytosis of L. lactis and Edwardsiella tarda by mIgM+ B lymphocytes. In addition, significantly higher intracellular reactive oxygen species (ROS) levels were detected in mIgM+ B lymphocytes following rIFN I-3 treatment. We also found that IFN I-3 significantly upregulated Stat1 expression in mIgM+ B lymphocytes, and the enhancing effect of IFN I-3 on mIgM+ B lymphocyte-mediated phagocytosis was suppressed by fludarabine treatment. Collectively, these results demonstrate that mIgM+ B cell-mediated phagocytosis in the Japanese flounder is effectively triggered by bacterial stimulation, and further enhanced by IFN I-3, which itself may be regulated by Stat1.

The (S)-adenosyl-L-methionine (SAM)-dependent methyltransferases play essential roles in post-translational modifications (PTMs) and other miscellaneous biological processes, and are implicated in the pathogenesis of various genetic disorders and cancers. Increasing efforts have been committed toward discovering novel PTM inhibitors targeting the (S)-Adenosyl-L-methionine (SAM)-binding site and the substrate-binding site of methyltransferases, among which virtual screening (VS) and structure-based drug design (SBDD) are the most frequently used strategies. Here, we report the development of a target-specific scoring model for compound VS, which predict the likelihood of the compound being a potential inhibitor for the SAM-binding pocket of a given methyltransferase. Protein-ligand interaction characterized by Fingerprinting Triplets of Interaction Pseudoatoms was used as the input feature, and a binary classifier based on deep neural networks is trained to build the scoring model. This model enhances the efficiency of the existing strategies used for discovering novel chemical modulators of methyltransferase, which is crucial for understanding and exploring the complexity of epigenetic target space.

Vibrio anguillarum is a pathogenic bacterium that infects flounder resulting in significant losses in the aquaculture industry. The VAA protein previously identified in flounder is associated with a role in immune protection within these fish. In the present study, a recombinant DNA plasmid encoding the VAA gene of V. anguillarum was constructed and its potential as a DNA vaccine, to prevent the infection of V. anguillarum in flounder fish, investigated. We verified the expression of the VAA protein both in vitro in cell lines and in vivo in flounder fish. The protective effects of pcDNA3.1-VAA (pVAA) were analyzed by determination of the percentage of sIgM+, CD4-1+, CD4-2+, CD8β+ lymphocytes, and the production of VAA-specific antibodies in flounder following their immunization with the DNA vaccine. Histopathological changes in immune related tissues, bacterial load, and relative percentage survival rates of flounder post-challenge with V. anguillarum, were all investigated to assess the efficacy of the pVAA DNA vaccine candidate. Fish intramuscularly immunized with pVAA showed a significant increase in CD4-1+, CD4-2+, and CD8β+ T lymphocytes at days 9, 11, and 14 post-vaccination, reaching peak T-cell levels at days 11 or 14 post-immunization. The percentage of sIgM+ lymphocytes reached peak levels at weeks 4–5 post-immunization. Specific anti-V. anguillarum or anti-rVAA antibodies were induced in inoculated fish at days 28–35 post-immunization. The liver of vaccinated flounder exhibited only slight histopathological changes compared with a significant pathology observed in control immunized fish. Additionally, a lower bacterial burden in the liver, spleen, and kidney were observed in pVAA protected fish in response to bacterial challenge, compared with pcDNA3.1 vector control injected fish. Moreover, the pVAA vaccine confers a relative percentage survival of 50.00% following V. anguillarum infection. In summary, this is the first study indicating an initial induction of the T lymphocyte response, followed by B lymphocyte induction of specific antibodies as a result of DNA immunization of flounder. This signifies the important potential of pVAA as a DNA vaccine candidate for the control of V. anguillarum infection.

CpG-oligodeoxynucleotides (CpG-ODNs) mimicking the function of microbial CpG-dideoxynucleotides containing DNA (CpG-DNA) are potent immune stimuli. The immunostimulatory activity and the species-specific activities of a CpG-ODN depend on its nucleotide sequence properties, including CpG-hexamer motif types, spacing between motifs, nucleotide sequence, and length. Toll-like receptor (TLR) 9 is the cellular receptor for CpG-ODNs in mammalian species, while TLR21 is the receptor in avian species. Mammalian cells lack TLR21, and avian cells lack TLR9; however, both TLRs are expressed in fish cells. While nucleotide sequence properties required for a CpG-ODN to strongly activate mammalian TLR9 and its species-specific activities to different mammalian TLR9s are better studied, CpG-ODN activation of TLR21 is not yet well investigated. Here we characterized chicken and duck TLR21s and investigated their activation by CpG-ODNs. Chicken and duck TLR21s contain 972 and 976 amino acid residues, respectively, and differ from TLR9s as they do not have an undefined region in their ectodomain. Cell-based TLR21 activation assays were established to investigate TLR21 activation by different CpG-ODNs. Unlike grouper TLR21, which was preferentially activated by CpG-ODN with a GTCGTT hexamer motif, chicken and duck TLR21s do not distinguish among different CpG-hexamer motifs. Additionally, these two poultry TLR21s were activated by CpG-ODNs with lengths ranging from 15 to 31 nucleotides and with different spacing between CpG-hexamer motifs. These suggested that compared to mammalian TLR9 and grouper TLR21, chicken and duck TLR21s have a broad CpG-ODN sequence recognition profile. Thus, they could also recognize a wide array of DNA-associated molecular patterns from microbes. Moreover, CpG-ODNs are being investigated as antimicrobial agents and as vaccine adjuvants for different species. This study revealed that there are more optimized CpG-ODNs that can be used in poultry farming as anti-infection agents compared to CpG-ODN choices available for other species.