Academic literature on the topic 'Bao gao wen xue'

BackgroundOutcomes for high grade serous ovarian cancer (HGSOC) patients have remained dismal due to the inevitable development of chemotherapy resistance with recurrent disease.1 In order to better tailor treatment approaches and uncover opportunities for novel treatments, we need to better understand factors contributing to chemotherapy resistance. Recent studies have shown that immune-related gene expression profiles may serve as prognostic indicators of response to chemotherapy and clinical outcomes in solid tumors, including ovarian cancer.2–7 Moreover, immunologic factors have been shown to mediate chemotherapy resistance8 Reports in the literature show that common ovarian cancer therapeutics, including chemotherapy, PARP inhibitors, and bevacizumab, modulate tumor cell expressed PD-L1 levels through immunologic signaling pathways.9–12 However, very little research has addressed the effect of these treatments on other immune ligands or the differences in immunologic responses between platinum-sensitive and platinum-resistant HGSOC cell lines.MethodsThe HGSOC cell lines OVCAR4 (naturally platinum-resistant), PEO1 and PEO4 (matched platinum-sensitive and -resistant lines from the same patient), were treated with common ovarian cancer therapeutics (carboplatin/paclitaxel, olaparib, and bevacizumab), in the presence or absence of peripheral blood mononuclear cells. Western blot was employed to identify levels of immune ligands of interest and a proteome profiler was used to detect broad immunologic changes in response to standard of care therapeutics.ResultsOlaparib and bevacizumab treatment strikingly upregulated levels of tumor cell expressed immune ligands ICOSL and PVRL2. Platinum status or presence of an immune component had no bearing on the effect. Moreover, blockade of PVRL2 using siRNA or monoclonal antibodies suppressed STAT3 signaling. When examining the effect of these therapeutics on cytokine levels in HGSOC cell lines treated in immune cell co-culture, OVCAR4 cells displayed marked changes in cytokine levels, particularly CXCL10, CXCL12, SERPINE1, IL1A, and IL1RA. While PEO1 and PEO4 cells displayed more subtle cytokine changes compared to OVCAR4 cells, differences in basal levels and treatment responses were observed between the platinum-sensitive and -resistant lines, most strikingly higher basal levels of SERPINE1 and CCL5/RANTES in PEO4 cells, and a robust increase in IL8 levels in response to chemotherapy in only PEO1 cells and not PEO4.ConclusionsIn conclusion, common ovarian cancer chemotherapeutics and targeted agents induce tumor cell intrinsic immunologic effects that could potentially be exploited as combinatorial therapeutic targets. Differences in immunologic responses may help define platinum-sensitive and -resistant disease. These results will require further exploration in immune-competent mouse models and human HGSOC tissue.ReferencesCortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol 2018;81(1):17–38.James NE, Miller K, LaFranzo N, Lips E, Woodman M, Ou J, Ribeiro JR. Immune modeling analysis reveals immunologic signatures associated with improved outcomes in high grade serous ovarian cancer. Front Oncol 2021;11:622182.Liu R, Hu R, Zeng Y, Zhang W, Zhou H-H. Tumour immune cell infiltration and survival after platinum-based chemotherapy in high-grade serous ovarian cancer subtypes: a gene expression-based computational study. EBioMedicine 2020;51:102602.Liu J, Meng H, Nie S, Sun Y, Jiang P, Li S, et al. Identification of a prognostic signature of epithelial ovarian cancer based on tumor immune microenvironment exploration. Genomics. 2020.Ding J, Zhang Q, Chen S, Huang H, He L. Construction of a new tumor immunity-related signature to assess and classify the prognostic risk of ovarian cancer. Aging (Albany, NY). 2020;12.Wu Y, Xia L, Zhao P, Deng Y, Guo Q, Zhu J, et al. Immune profiling reveals prognostic genes in high-grade serous ovarian cancer. Aging (Albany, NY). 2020;12(12):11398–11415.Montfort A, Owen S, Piskorz AM, Supernat A, Moore L, Al-Khalidi S, et al. Combining measures of immune infiltration shows additive effect on survival prediction in high-grade serous ovarian carcinoma. Br J Cancer 2020;122(12):1803–1810.Liu W, Wang Y, Xie Y, Dai T, Fan M, Lu C, Zou Y. Cisplatin remodels the tumor immune microenvironment via the transcription factor EB in ovarian cancer. Cell Death Discov. 2021;7(1):136.Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, Yamaguchi K, Horikawa N, Hosoe Y, Murphy SK, Konishi I, Mandai M. Chemotherapy induces programmed cell death-Ligand 1 overexpression via the nuclear factor-κB to foster an immunosuppressive tumor microenvironment in Ovarian cancer. Cancer Res 2015;75(23):5034–45.Jiao S, Xia W, Yamaguchi H, Wei Y, Chen M-K, Hsu J-M, et al. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res 2017;23(14):3711–3720.Xue C, Xu Y, Ye W, Xie Q, Gao H, Xu B, et al. Expression of PD-L1 in ovarian cancer and its synergistic antitumor effect with PARP inhibitor. Gynecol Oncol 2020;157(1):222–233.Zhang L, Chen Y, Li F, Bao L, Liu W. Atezolizumab and bevacizumab attenuate cisplatin resistant Ovarian cancer cells progression synergistically via suppressing epithelial-Mesenchymal transition. Front Immunol 2019;10:867.

Abstract Acute myeloid leukemia (AML) is an aggressive leukemia of myeloid lineage with different subtypes of varying treatments/outcomes and a global annual mortality ~150,000. The first-line treatment of AML is usually induction chemotherapy, followed by further chemo-/radiation therapies or stem cell transplant. Targeted therapy tailored for specific driver mutations could be alternative treatment options, e.g., new inhibitors targeting IDH mutations and FLT3-ITR CSF1R is a receptor tyrosine kinase (RTK) responsible for the growth, survival and polarization of certain myeloid lineages of cells including macrophages. It is also frequently expressed in certain AML patient populations, thus implicated in the pathogenesis, or a new possible drug target of AML. To test this hypothesis, a novel kinase inhibitor, HX301 with strong anti-CSF1R activity (IC50 of ~0.7nM) as well as anti-FLT3 (IC50 of ~7nM), were assessed for anti-AML activity. First, an in vitro proliferation assay was performed using primary macrophages and a panel of AML cell lines, confirming that HX-301 has high potency in primary macrophage culture (IC50 of ~70nM) and also among cultures of a subsets of AML lines (e.g. IC50 < 1µM), such as MV4-11 (medium CSF1R expressing and FLT3-ITD), EOL1, MOL13, etc. Next, HX301 was pharmacologically modeled using four preclinical models to test anti-leukemia activity in vivo, including subcutaneous xenograft of MV4-11 cells (CDX) and systemically engrafted PDX models AM8096 (high CSF1R expression but wild type FLT3), AM7577 (FLT3-ITD but little CSF1R expression) and AM5512 (wild-type FLT3 and little CSF1R expression). Our data demonstrated that HX301 partially inhibited MV4-11 tumor growth as measured by tumor volume, consistent with the in vitro observation, possibly due to the inhibition of CSF1R or FLT3-ITD, or both. On the other hand, HX301 completely suppressed leukemogenesis of AM8096, likely due to the inhibition of CSF1R. This observation suggested that CSF1R is likely the driving mechanism for the leukemogenesis of this model; or in another word, for being a PDX, CSF1R likely drives pathogenesis in the original patient. HX301 also suppressed AM7577 growth, likely due to the suppression of FLT3-ITD activity since we previously reported FLT3-ITD being the driver mutation in this model which responded to AC220, a FLT3 TKi. Lastly, HX301 has little activity against AM5512. All the data suggests that HX301 can potentially be explored for the treatment of AML, at least a subset of the patients with CSF1R and FLT3-ITD as leukemogenic drivers. Further preclinical/translational studies are being conducted in order to reveal predictive biomarkers, in addition to FLT3 mutation and CSF1R expression/mutations. We believe that HX301 could be a potential candidate for treating subset of AML, warranting further clinical investigation. Citation Format: Xiaoyu An, Henry Li, Linda Xue, Jinping Liu, Lingxin Xiong, Hang Ke, Cen Chen, Bing Gao, Jia Zheng, Zhengzheng Bao, Sheng Guo, Lei Zhang, Faming Zhang. HX301 (ON1232580) a novel kinase inhibitor with potent activity against CSF1R and FLT3, shows strong anti-AML activity in defined preclinical models. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5665.

Alkaline water electrolysis (AWE) is a promising technology for carbon capture [1]. Anion exchange membrane water electrolyzers (AEMWEs) utilize low-cost, non-precious metal materials, providing an economically viable alternative to more expensive proton exchange membrane water electrolyzers (PEMWEs). While PEMWEs can operate at much higher current densities, they require noble metal catalysts and titanium components for the high potential environment anode [1]. The implementation of a bipolar membrane (BPM) will allow both HER and OER to occur under kinetically favorable conditions [2, 3] by combining both thin AEM and thin PEM layers within a single membrane. AEMs, PEMs, and BPMs have been tested in CO2RR electrolyzers [4]. The BPM may provide a pathway to combine the advantages of both AEMs and PEMs for CO2 reduction. Altering both the membrane and CCM is a focus in the research and development in CO2RR electrolyzers. Lee et al. [5] explored the use of a porous membrane for CO2 reduction. While work can be done to improve performance and crossover, the porous membrane provided excellent mechanical properties and good economic potential. There has been some work done on developing bifunctional membranes for water electrolysis and CO2 reduction [3, 6, 7]. Two key issues with operation of a CO2RR electrolyzer with a BPM is the reactant CO2 that is lost to the AEM and PEM membrane layer interface and the instability of the cell. Both issues contribute to a significant decrease in performance and faradaic efficiency in product conversion. Development of the BPM, both on the membrane’s fabrication and configuration, and electrode layers, needs to be explored to reach higher performances and longer lifespans. In this work, reactive spray deposition technology (RSDT) was used to fabricate electrodes on a UConn fabricated bipolar membrane. Testing of each configuration was conducted as both an AEM water electrolyzer and CO2RR electrolyzer. Polarization, electrochemical impedance spectroscopy, electrochemical equivalent circuits, and distribution of relaxation times were used to investigate cell performance and durability. References [1] B. Mayerhofer, D. McLaughlin, T. Bohm, M. Hegelheimer, D. Seeberger, and S. Thiele, “Bipolar membrane electrode assemblies for water electrolysis,” ACS applied energy materials, vol. 3, no. 10, pp. 9635–9644, 2020. [2] J. Xu, I. Amorim, Y. Li, J. Li, Z. Yu, B. Zhang, A. Araujo, N. Zhang, and L. Liu, “Stable overall water splitting in an asymmetric acid/alkaline electrolyzer comprising a bipolar membrane sandwiched by bifunctional cobalt-nickel phosphide nanowire electrodes,” Carbon Energy, vol. 2, no. 4, pp. 646–655, 2020. [3] Q. Lei, B. Wang, P. Wang, and S. Liu, “Hydrogen generation with acid/alkaline amphoteric water electrolysis,” Journal of Energy Chemistry, vol. 38, pp. 162–169, 2019. [13] W. H. Lee, K. Kim, C. Lim, Y. J. Ko, Y. J. Hwang, B. K. Min, U. Lee, and H. S. Oh, “New strategies for economically feasible CO2 electroreduction using a porous membrane in zero-gap configuration,” Journal of Materials Chemistry A, vol. 9, pp. 16169–16177, 8 2021 [4] D. A. Salvatore, C. M. Gabardo, A. Reyes, C. P. O’Brien, S. Holdcroft, P. Pintauro, B. Bahar, M. Hickner, C. Bae, D. Sinton, E. H. Sargent, and C. P. Berlinguette, “Designing anion exchange membranes forCO2 electrolysers,” Nature Energy, vol. 6, pp. 339–348, 4 202 [5] W. H. Lee, K. Kim, C. Lim, Y. J. Ko, Y. J. Hwang, B. K. Min, U. Lee, and H. S. Oh, “New strategies for economically feasible CO2 electroreduction using a porous membrane in zero-gap configuration,” Journal of Materials Chemistry A, vol. 9, pp. 16169–16177, 8 2021 [6] W. Li, Z. Yin, Z. Gao, G. Wang, Z. Li, F. Wei, X. Wei, H. Peng, X. Hu, L. Xiao, J. Lu, and L. Zhuang, “Bifunctional ionomers for efficient CO electrolysis of CO2 and pure water towards ethylene production at industrialscale current densities,” Nature Energy, 2022 [7] C. P. O’Brien, R. K. Miao, S. Liu, Y. Xu, G. Lee, A. Robb, J. E. Huang, K. Xie, K. Bertens, C. M. Gabardo, et al., “Single pass CO2 conversion exceeding 85% in the electrosynthesis of multicarbon products via local CO2 regeneration,” ACS Energy Letters, vol. 6, no. 8, pp. 2952–2959, 2021.

Objective: To assess the relationship between Helicobacter pylori (Hp) infection and primary open-angle glaucoma (POAG); and meantime, to explore the possible mechanism of POAG induced by Hp. Methods: 30 consecutive POAG patients, 30 primary angle-closure glaucoma (PACG) and cataract patients were recruited and divided into three groups according to different diseases. The sera and aqueous humor samples were collected and used to detect Hp-specific IgG antibody (Hp-Ab) with dot immunogold filtration assay (DIGFA). 14C-urea breath test (14C-UBT) was carried out to detect Hp infection of all participants. Results: The Hp-Ab positive rate respectively was 76.7% (23/30) and 66.7% in sera samples and aqueous humor samples for POAG group, which was significantly higher than the corresponding data of the other two groups (all P<0.05). In 14C-UBT, the Hp-Ab positive rate was 63.3% in POAG group and it was close to that of serological result detected by DIGFA (P>0.05). There were little numbers of positive ANA and ENA in the three groups and no meaning to make statistically analysis. Conclusions: There is positive association between Hp infection and POAG, and the autoimmune is suggested as one of the key mechanisms in our opinions. Introduction Glaucoma is one of the commonest causes for blindness in the world. Generally, glaucoma is divided into primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG).1 As a leading causes for blindness, the study of POAG causes more and more attention.2,3To our understand, POAG is a chronic optic neuropathy characterized by atrophy and increased cupping of optic disk. To date, many aspects of its pathogenesis remain unknown but some significant risk factors are advanced age, African origin, familial history of glaucoma and elevated intraocular pressure.4,5 Helicobacter pylori (Hp) is a Gram-negative and microaerophilic bacterium which plays an important role in the development of various upper gastrointestinal diseases. With the development of studies, some researchers reported that Hp was also associated with some extragastric diseases, such as ischemic heart disease,6 iron-deficient anemia,7 diabetes mellitus,8 and so on. In 2001, Kountouras et al9 established a higher prevalence of Hp infection in the sera of patients with POAG in a Greek population, and suggested a possible causal link between Hp and glaucoma. Subsequently, this finding was evidenced by some scholars in their own studies.10 But the significance of such an association remains uncertain because of the conflicting findings reported by various studies.11-13 Aiming to such a discrepancy, further studies are necessary.14 In this study, we just do detect Hp-specific IgG antibodies (Hp-Ab) in the sera and aqueous humor of patients with different ocular diseases, including POAG, PACG and cataract, and attempt to further determine the relationship between Hp infection and POAG and to analyze the possible mechanism of POAG induced by Hp. Abbreviations ANA, antinuclear antibody; ENA, Extractable nuclear antigen; DIGFA, dot immunogold filtration assay; Hp, Helicobacter pylori; Hp-Ab, Hp-specific IgG antibodies; PACG, primary angle-closure glaucoma; POAG, primary open-angle glaucoma; 14C-UBT: 14C-urea breath test. Subjectsand methods Subjects 30 consecutive POAG patients were enrolled with the average age of 68±7.3 y (ranged from 47 to 78 y). The ratio of the male and the female was 11: 19. Meantime, 30 PACG patients and 30 cataract patients were also recruited, and who were matched by age and sex with the POAG patients. According to different diseases, the participants were divided into POAG, PACG and cataract groups, respectively. All of them were excluded from tumor, immunodeficiency, autoimmune and infectious diseases in clinic, and also had no antibiotics and other medicines related to immunopotentiator or immunosuppressive agents in the six months before the experiment. Written informed consents were obtained from all the participants. The study was approved by the local ethics committee. Hp-Ab detection of sera samples 2 ml venous blood was collected from each of the participants. The serum was obtained after centrifugation and used to detect Hp-Ab with dot immunogold filtration assay (DIGFA) according to the manufacturer’s instruction of the reagent kit (MP Biomedicals Asia-Pacific Pte. Ltd., Singapore). Hp-Ab detection of aqueous humor samples About 50 μl aqueous humor sample was aspirated at the beginning of glaucoma surgery from the each of the patients in the three groups, respectively. Hp-Ab was assayed with DIGFA as same as the detection process of venous blood samples. Detection of Hp infection with 14C-urea breath test Referring to Tang’s report,1514C-urea breath test (14C-UBT) was carried out in POAG group with Hp detection instrument-YH04 (Yanghe Medical Equipment Co. Ltd., China). Sera auto-antibodies detection Serum antinuclear antibody (ANA) was detected with the indirect immunofluorescence assay by a commercialized ANA kit. Extractable nuclear antigen (ENA) was assayed with line immunoassay. All reagents were bought from Jiangsu HOB Biotech Group, China. Statistic analysis Using T-test and Chi-square test, all analyses were performed with SPSS 13.0 software. P value less than 0.05 were considered significant. Results 3.1 Hp infection detection in sera and aqueous humor Of the sera samples, there were 23 cases exhibited Hp-Ab-positive in POAG group, and the positive rate was 76.7% which was significantly higher than those of PACG and cataract group (43.3% and 36.6% respectively). In the aqueous humor samples, there were 18 patients with positive Hp-Ab in POAG group, and the positive rate was 66.7%. Compared to each data of the other two groups, the difference was statistically significant (Table 1). In POAG group, the mean positive rate of sera samples was similar to that of aqueous humor and no difference existed between them (P = 0.287). Table 1. The serum and aqueous humor qualitative test results of the patients with glaucoma Hp infection detection with 14C-UBTAH: aqueous humor; a: POAG group vs cataract group; b: POAG group vs PACG group; c: PACG group vs cataract group. In 14C-UBT, there were 19 patients with Hp-Ab-positive, and the positive rate was 63.3%. Compared to the data detected with DIGFA, the difference was not significant (Table 2). Table 2. Comparison of DIGFA and 14C-UBT for diagnosis of Hp infection in POAG group ANA and ENA detection* represents comparison of the positive rate detected with the two methods. There were 4, 2 and 1 patients with ANA-positive in POAG, PACG and cataract group, respectively. The positive ENA in POAG group were SSA, SSB and Ro-52, and the corresponding numbers were 2, 2 and 1. Only Ro-52 showedpositive in PACG group while there was no positive ENA in cataract group (Table 3). Table 3. The results for sera ANA, ENA of the patients of each group Discussion In Greece, a very active research group led by J. Kountouras published several original contributions as well as the reviews concerning the connection between Hp infection and POAG.14,16 In other counties, there were also several papers containing the similar arguments issued, such as India,17 Turkey,18 Korea19 and so on. In China, Hong et al20 detected Hp infection and POAG through 13C-UBT, and also found the positive correlation between them. Since then, there was no relative article issued by Chinese could be found in PubMed and other well-known scientific database. In this study, referring to other researchers’ reports, we designed and carried out the experiments. In the results, we found that the positive rate of sera Hp-Ab was high to 76.7% in POAG patients, which was significantly higher than those of the other two groups. This finding was close to the data of the previous reports2,21 and further verified that there was a positive relation between Hp infection and POAG. In the present study, we also assayed Hp infection with 14C-UBT. Encouragingly, the positive rate of Hp infection was 63.3%, which was very close to 76.7% detected with DIGFA. This result further indicated the existence of the relation between Hp infection and POAG. However, Bagnis et al22 thought that the studies based on Hp serological assessment might be misleading, since serum antibodies were not the sensitive markers of active Hp infection; while 13C-UBT could clarify the actual prevalence of POAG among patients infected by Hp. In fact, there were still deficiencies for 13C- or 14C -UBT, because it was more suitable for the detection of gastrointestinal Hp infection, and to an extent, there were false-negatives in the test.23 This probably was the just reason for what the positive rate in DIGFA was little higher than that in 14C-UBT in this study. As to the cresyl fast violet staining on the histology preparations of tissue samples of trabeculum and iris introduced by Zavos et al,24 although it could provide the direct and strong evidence for Hp infection in the pathophysiology of POAG, the difficult harvest of the sample limited its application. Therefore, in our opinions, the serological assay is suitable to detect Hp infectionand used to assess the relationship between Hp prevalence and POAG. Except for detecting sera Hp-Ab, we also detected Hp-Ab in the aqueous humor collected from the majority of participants. As the results shown, the positive rate of the POAG group was statistically higher than each of the other groups, respectively. This result was consistent with that of the serological assessment and again showed the positive relation between Hp infection and POAG. However, in another similar study, Deshpande et al17 also found a statistically significant difference between the POAG patients and the controls in the concentration of serum Hp-Ab, but they did not find any significant correlations between the Hp concentrations of the aqueous humor of the different patient groups. This disagreement probably associated with the damage degree of blood-brain barrier (BBB), because the sera Hp-Ab could reach the trabeculum and iris under the condition of the BBB disruption.25 According to the results of the present study, we supported the hypothesis related to POAG onset that Hp-Ab in circulation might get through the blood-aqueous humor barrier, further condensed in aqueous humor and finally induced or aggravated glaucomatous damage.2 As to the occurrence of POAG, we thought another autoimmune mechanism was most probable and should not be ignored: Hp infection initiated autoimmune response because of the common genetic components shared in Hp and human nerve tissue; and then, cell destruction which mediated by apoptosis direct caused glaucoma.26 Just based on the theory, we designed and detected sera ANA and ENA of the POAG patients and the control participants, and hoped to find any evidences related to autoimmune. As a result, we found that the positive rate of every group was rather low and there was no difference between them. However, this seronegative result can’t deny the hypothesis of autoimmune mechanism in POAG; and the auto-antibodies specific to eyes, such as trabeculum and iris, were suggested to be detected in future study in our opinions. Conclusion The positive association between Hp infection and POAG not only using serum sample but also aqueous humor sample is found in this study. And further, through the experimental data, it is suggested that the autoimmune induced by Hp infection probably is the key mechanism for POAG onset, and Hp detection should be taken as a routinized index applied to the prevention and therapy of POAG in clinic. However, we can not sufficiently investigate the possible mechanism of POAG relates to Hp infection. Is it true that Hp infection only relative to POAG but not a causative factor for POAG?18 What are the initial mechanisms of Hp in POAG if the pathogen takes part in the onset of the disease? Such questions will be the study topics to the medical researchers worldwide in future. Funding This work is supported by the Research Fund for Lin He’s Academician Workstation of New Medicine and Clinical Translation in Jining Medical University(JYHL2018FMS08), and the Project of scientific research support fund for teachers of Jining Medical University (JYFC2018FKJ023). Conflicts of interest There is no any conflict of interest between all of the authors. References: Chan H. H.; Ng Y.F.; Chu P. H. Clin Exp Optom. 2011, 94, 247. Kountouras J.; Mylopoulos N.; Konstas A. G.; Zavos C.; Chatzopoulos D.; Boukla A. Graefe’s Arch Clin Exp Ophthalmo. 2003, l241, 884. Kim E. C.; Park S. H.; Kim M. S. A. J. Pharmacol. Ther. 2010, 26, 563. Cantor L.; Fechtner R. D.; Michael A. J. San Francisco: Foundation of American Academy of Ophthalmology. 2005, 8. Bron A.; Chaine G.; Villain M.; Colin J.; Nordmann J. P.; Renard, J.P.; et al. Fr. Ophtalmol. 2008, 31, 435. Suzuki H.; Franceschi F.; Nishizawa T.; Gasbarini A. Helicobacter. 2011, 16, 65. Xia W.; Zhang X.; Wang J.; Sun C.; Wu L. Br. J. Nutr. 2011, 18, 1. Schimke K.; Chubb S. A.; Davis W. A.; Davis T. M. Atherosclerosis. 2010, 212, 321. Kountouras J.; Mylopoulos N.; Boura P.; Bessas C.; Chatzopoulos D.; Venizelos J.; et al. Opthalmology. 2001, 108, 599. Zaidi M.; Jilani A.; Gupta Y.; Umair S.; Gupta M. Nep. J. Oph. 2009, 1, 129. Galloway P. H.; Warner S. J.; Morshed M. G.; Mikelberg F. S. Ophthalmology. 2003, 110, 922. Abdollahi A.; Zarei R.; Zare M.; Kazemi A.Iran J. Opththalmol. 2005, 18, 15. Kurtz S.; Regenbogen M.; Goldiner I.; Horowitz N.; Moshkowitz M. Glaucoma. 2008, 17, 223. Tsolakin F.; Gogaki E.; Sakkias F.; Skatharoudi C.; Lopatatzidi C.; Tsoulopoulos V.; et al. Ophthalmol. 2012, 6, 45. Tang H. R.; Fan Y. J.; Liu S. Sichuan Da Xue Xue Bao Yi Xue Bao. 2014, 45, 823. Zavous, C.; Kountouras, J. Ophthalmol. 2012, 6, 243. Deshpande N.; Lalitha P.; Krishna das S. R.; Jethani J.; Pillai R. M.; Robin A.; et al. Glaucoma. 2008, 17, 605. Öztürk F.; Kurt E.; Inan U. U.; Erm S. S.; Çetinkaya Z.; Altýndi M. African J. Res. 2009, 3, 560. Kim J. M.; Kim S. H.; Park K. H.; Han S. Y.; Shim H. S. Invest Ophthalmol. Vis. Sci. 2011, 52, 665. Hong Y.; Zhang C. H.; Duan L.; Wang E. Asian J. Ophthalmol. 2007, 9, 205. Samarai V.; Shrif N.; Nateghi S. Glob. J. Health Sci. 2014, 6, 13. Bagnis A.; Izzotti A.; Saccàn S. C. Diagestive and Liver Disease. 2012, 44, 962. Gao F.; Li W. X. Chin. J. Gastroenterol. 2015, 20, 151. Zavos C.; Kountouras J.; Sakkias G.; Venizelos L.; Deretzi G.; Arapoglou, S. Res. 2012, 47, 150. Kountouras J.Br. J. 2009, 93, 1413. Kountouras J.; Gavalas E.; Zavos C.; Stergiopoulos C.; Chatzopoulos D.; Kapetanakis N.; et al. . Hypotheses. 2007, 68, 378.

Introdução: O câncer é definido como uma proliferação descontrolada de células malignas em um hospedeiro e considerado uma das principais causas de morte em todo o mundo. No Brasil, o câncer colorretal é a segunda causa de morte mais comum entre mulheres e a terceira mais prevalente em homens. Muitas estratégias têm sido estudadas para auxiliar o tratamento antineoplásico. Dentro desse contexto, a ingestão de probióticos, representa uma nova opção terapêutica relevante no âmbito da nutrição. Objetivo: Realizar uma revisão sobre o uso dos probióticos no tratamento de pacientes com câncer colorretal. Material e Método: Trata-se de uma revisão realizada em 2018, utilizando-se 10 artigos, pesquisados nas bases indexadas BVS e PubMed e na ferramenta de pesquisa Google acadêmico. A pesquisa incluiu artigos em português e inglês publicados no período de 2010 a 2017. Resultados: O uso de probióticos demonstrou trazer efeitos positivos ao tratamento de pacientes com câncer colorretal, trazendo benefícios como: a diminuição de enterobactérias e enterococos, melhora na modulação da imunidade local, melhora dos sintomas intestinais, recuperação da função intestinal, entre outros. Conclusão: Conclui-se que apesar dos resultados positivos observados, há a necessidade de futuros estudos de longa duração para elucidar melhor essa relação.Descritores: Neoplasias Colorretais; Nutrientes; Probióticos.ReferênciasKahouli I, Malhotra M, Westfall S, Alaoui-Jamali MA, Prakash S. Design and validation of an orally administrated active L. fermentum-L. acidophilus probiotic formulation using colorectal cancer Apc Min/+ mouse model. Appl Microbiol Biotechnol. 2017;101(5):1999-2019.Oliveira RC, Rêgo MAV. Mortality risck of colorectal câncer in Brazil from 1980 to 2013. Arq Gastroenterol 2016;53(2)76-83.Instituto Nacional de Câncer (INCA). Tipos de câncer: colorretal. Rio de Janeiro: INCA; 2018.Instituto Nacional de Câncer (INCA). Estimativa 2016: incidência de Câncer no Brasil. Rio de Janeiro: INCA; 2016.Brasil. Ministério da Saúde. Departamento de Informática do SUS (DATASUS). Painel de Monitoramento da Mortalidade CID-10. Brasília; 2017.Corrêa RS, Pinto JRFE, Santos LV, Góis MC, Silva RP, Silva HM. Rectal cancer survival in a Brazilian Cancer Reference Unit. J Coloproctol. 2016;36:203-7.Oliveira AL, Aarestrupo FM. Avaliação nutricional e atividade inflamatória sistêmica de pacientes submetidos à suplementação com simbióticos. ABCD arq bras cir dig. 2012;25(3):147-53.Jacoby JT, Guzzon S, Rosech LFW, Mendes RH. Uso de pré, pró e simbióticos como coadjuvantes no tratamento do câncer colorretal. Clin Biomed Res. 2017;37(3):232-46.Gao Z, Guo B, Gao R, Zhu Q, Wu W, Qin H. Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer. Mol Med Rep. 2015;12(4):6119-27.Chaves PL, Gorini MI. 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Randomised clinical trial: the effects of perioperative probiotic treatment on barrier function and postoperative infectious complications in colorectal câncer surgery – a double-blind study. Aliment Pharmacol Ther. 2011;33(1):50-63.Yang Y, Xia Y, Chen H, Hong L, Feng J, Yang J et al. The effect of perioperative probiotics treatment for colorectal cancer: short-term outcomes of a randomized controlled trial. Oncotarget. 7(7);8432-40.Kotzampassi K, Stavrou G, Damoraki G, Georgitsi M, Basdanis G, Tsaousi G et al. A four-Probiotics regimen reduces postoperative complications after colorectal surgery: a randomized, double-blind, placebo-controlled study. World J Surg. 2015;39(11):2776-83.Lee JY, Chu SH, Jeon JY, Lee MK, Park JH, Lee DC et al. Effects of 12 weeks of probiotic supplementation on quality of life in colorectal cancer survivors: a double-blind, randomized, placebo-controlled trial. 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This study identifies A10398G alteration of mitochondrial ND3 gene in plasma exosome of 29 non-small cell lung cancer (NSCLC) patients, 31 controls and 13 pairs of tumor tissue and adjacent tissue of NSCLC patients, thereby assessing the relationship between this alteration in plasma exosome and tissue as well as the pathological characteristics of NSCLC patients. Using the PCR-RFLP method, the homoplasmy and heteroplasmy of A10398G were initially identified in mitochondrial DNA from both exosomes and lung tissues. The rate of variant 10398G in plasma exosome was 62.1% in the NSCLC group and 61.3% in the control group. However, there was no statistically significant difference in A10398G between the patient and control groups. The alteration of A10398G in plasma exosome and in tissue correlated with each other (correlation coefficient 0.69; p = 0.009). However, this alteration was not related to age, gender, smoking, alcohol drinks status, tumor size, histological stage and TNM stage. Keywords A10398G alteration, mitochondrial DNA, plasma exosome, non-small cell lung cancer. References [1] Y. Zhang, Y. Liu, H. Liu, W.H. Tang, Exosomes: biogenesis, biologic function and clinical potential, Cell Biosci, 9 (2019) 19. https://doi.org/10.1186/s13578-019-0282-2.[2] H. Valadi, K. Ekström, A. Bossios, M. Sjöstrand, J.J. Lee, J.O. Lötvall, Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells, Nat Cell Biol, 9(6) (2007) 654–659. https://doi.org/10.1038/ncb1596.[3] A. Sharma & A. Johnson, Exosome DNA: Critical regulator of tumor immunity and a diagnostic biomarker, J Cell Physiol, 235(3) (2020) 1921–1932. https://doi.org/10.1002/jcp.29153.[4] Global Cancer Observatory, Cancer Today. https://gco.iarc.fr/today/online-analysis-pie. (accessed 05 November 2020).[5] A.A.M. Yusoff, F.N. Zulfakhar, S.Z.N.M. Khair, W.S.W. Abdullah, J.M. Abdullah, Z. 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Millikan, Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women, Cancer Res 65(17) (2005) 8028-8033. https://doi.org/10.1158/0008-5472.can-05-1428.[10] K. Darvishi, S. Sharma, A.K. Bhat, E. Rai, R.N.K. Bamezai, Mitochondrial DNA G10398A polymorphism imparts maternal Haplogroup N a risk for breast and esophageal cancer, Cancer Letts 249(2) (2017) 249-255. https://doi.org/10.1016/j.canlet.2006.09.005.[11] S.H.H. Juo, M.Y. Lu, R.K. Bai, Y.C. Liao, R.B. Trieu, M.L. Yu, L.J.C Wong, A common mitochondrial polymorphism 10398A>G is associated metabolic syndrome in a Chinese population, Mitochondrion 10(3) (2010) 294-299. https://doi.org/10.1016/j.mito.2010.01.001.[12] H. Xu, W. He, H.G. Jiang, H. Zhao, X.H. Peng, Y.H. Wei, J.N. Wei, C.H. Xie, C. Liang, Y.H. Zhong, G. Zhang, D. Deng, Y.F. Zhou, F.X. 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In this paper, we analyze an underlay two-way decode-and-forward scheme in which secondary relays use successive interference cancellation (SIC) technology to decode data of two secondary sources sequentially, and then generate a coded signal by superposition coding (SC) technology, denoted as SIC-SC protocol. The SIC-SC protocol is designed to operate in two time slots under effects from an interference constraint of a primary receiver and residual interference of imperfect SIC processes. Transmit powers provided to carry the data are allocated dynamically according to channel powers of interference and transmission, and a secondary relay is selected from considering strongest channel gain subject to increase in decoding capacity of the first data and decrease in collection time of channel state information. Closed-form outage probability expressions are derived from mathematical manipulations and verified by performing Monte Carlo simulations. An identical scheme of underlay two-way decodeand-forward relaying with random relay selection and fixed power allocations is considered to compare with the proposed SIC-SC protocol, denoted as RRS protocol. Simulation and analysis results show that the non-identical outage performances of the secondary sources in the proposed SIC-SC protocol are improved by increasing the number of the secondary relays and the interference constraint as well as decreasing the residual interference powers. Secondly, the performance of the nearer secondary source is worse than that of the farther secondary source. In addition, the proposed SIC-SC protocol outperforms the RRS comparison protocol, and effect of power allocations through channel powers is discovered. Finally, derived theory values are precise to simulation results. Keywords: Successive interference cancellation, superposition coding, power allocation, underlay cognitive radio, non-orthogonal multiple access, outage probability. 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The globe is engulfed by one of the most extensive public health crises as COVID-19 has become a leading cause of death worldwide. COVID-19 was first detected in Wuhan, China, in December 2019, causing the severe acute respiratory syndrome. This review discusses issues related to Covid-19 vaccines, such as vaccine development targets, vaccine types, efficacy, limitations and development prospects. Keywords: Covid-19, SARS-CoV-2, vaccine, spike protein. References [1] C. Wang, P. W. Horby, F. G. Hayden, G. F. Gao, A Novel Coronavirus Outbreak of Global Health Concern, The Lancet, Vol. 395, No. 10223, 2020, pp. 470-473, https://doi.org/10.1016/S0140-6736(20)30185-9.[2] T. Singhal, A Review of Coronavirus Disease-2019 (COVID-19), The Indian Journal of Pediatrics, Vol. 87, 2020, pp. 281-286, https://doi.org/10.1007/s12098-020-03263-6.[3] World Health Organization, WHO Coronavirus (COVID-19) Dashboard, https://covid19.who.int/, (accessed on: August 21st, 2021).[4] A. 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In the Reform Proposals for the Education in Hong Kong published in 2000, it was clearly stated that the priotity of education in the 21st century should be ―to enable our students to enjoy learning, enhance their effectiveness in communication and develop their creativity and sense of commitment‖. This paper aims to respond to two of the aspects — the enhancement of effectiveness in communication and the development of students’ creativity. For years, schools have focused on promoting students’ creavity in reading and writing, but not in speaking. In fact, among the various language skills, ‘speaking’ is the skill students have to demonstrate the most in their daily interaction. Compared to reading and writing, the ability to express one‘s views verbally in a creative manner can give rise to more direct interaction, acting as a genuine reflection of a student’s wisdom, knowledge, capability and potential. It is also a lifelong skill that students can apply when they join the workforce in the future. It is therefore meaningful to place emphasis on cultivating students’ creativity in speaking. This research aims to explore the correlation between the Chinese oral proficiency and creative ability of senior secondary students in Hong Kong based on existing theories on the development of creativity and speaking. Target participants, recruited from two aided secondary schools of different abilities, receive training on speaking and creative thinking, and analysis is done adopting both the quantitative and qualitative approaches. Students of each school are first randomly divided into two groups — the experimental group and control group. Students of both groups are required to take a pre-test and a post-test, as well as complete a set of questionnaire in each session. Results obtained are compared and contrasted to gauge the changes in their oral proficiency and creative ability. In between the tests, the experiemental group receives seven experimental design lectures on News and Report, one of the elective modules of the NSS curriculum in Chinese Language Education, while the control group receives lectures on News and Report which reference on the samples from Education Bureau only, no experimental design lectures will be delivered. In the end, the three teachers involved in the study were interviewed, during which the teachers offered their observations on the change in the students’ learning behaviour and attitude. Based on the data collected from the administration of tests, questionnaires and interviews, the following conclusions are made: first, there is a correlation between oral proficiency and creative ability; second, students’ attitude and values have a direct impact on the effectiveness of the module; third, the Speaking and Creativity Assessment rubric used in the study proved to be successful in assessing the said abilities, enhancing learning effectiveness. Through the analysis of data collected, this research contributed to Chinese Language Education to some extent, especially in the teaching of oral proficiency and creativity. It opened up a new set of criteria for the assessment of creative speaking ability from different perspectives to ensure objectivity of results, offered diversified course materials that can effectively raise the standard of students’ speaking and critical thinking ability. 香港在2000 年教育制度改革建議中明確指出教育首要目標是培養學生成為「樂於學習、善於溝通、勇於承擔、敢於創新」的新一代，其中，本研究特別回應「善於溝通」和「敢於創新」這兩個重點。過往，學校及教師多注重學生閱讀能力及寫作能力創意的培養，而忽略說話能力的創意訓練。其實，在各種語文能力中，「說話」是學生日常生活最主要的表達能力。口語表達比閱讀及寫作語言起著更直接的交流及溝通作用，是一個人智慧、知識、能力、素質的綜合體現，是學生立足社會、終生受用的語文能力。因此語文教學以創意思維培養學生的說話能力是有實在意義的。 為探索本港高中學生口語表達和創意能力的相互關係，本研究以創造力(Creativity) 和說話能力訓練的理論為依據，對上述課題展開試驗及分析工作。本計劃以香港兩所不同程度的津貼中學學生的說話能力為研究對象， 施行融合創意和說話能力訓練的實驗教學模式。本研究採用量化和質化方式為主要研究的方法。首先， 每所學校的研究對象隨機分為實驗組 (Experimental Group) 和控制組 (Control Group)。兩組對象分別安排前測和後測來量度實驗前後的數據變化。在前測及後測之間， 實驗組將會進行結合了創意思維訓練元素的中國語文選修單元「新聞與報道」共七節課的教學，從而探究這次實驗課能否提高學生創意說話能力學習的成效。而控制組卻不會在實驗教學施行期間安排進行任何實驗教學，有關的課堂教學，只按照原本學校的「新聞與報道」課程進行。在公平的原則下，所有控制組的學生會在暑假補回教授有關的實驗課程知識。本研究同時在兩班實驗組學生發出前後兩次的問卷調查，以檢視受試者的說話能力及創意能力的變化。最後，訪問兩所受試學校參與研究的三位老師，以深入瞭解學生整體的學習行為和態度情意的改變。 透過分析實驗教學資料、問卷調查數據和訪談結果，本研究主要有以下幾方面的總結：第一，確立說話能力和創意能力的相互關係。第二，學生的學習態度和品德情意直接影響課程的學習成效。第三，本研究所採用的「說話及創意能力評量表」能客觀評估學生的說話及創意能力，促進學習效能。經各種測試及結果分析，本研究對中國語文教育作出了一些貢獻，尤其是在融合說話與創意能力方面，以提高學生說話和思考水平；開發創意說話能力的評核標準，包含多角度的評審考量為評核精神，以客觀的等級描述為評量依據；提供多元化的創意說話課程設計，有助提升學生的創意說話能力表現等多方面的意義。
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One of the most famous radioisotopes used in nuclear medicine is Iodine-123. Among the various types of nuclear reactions for producing I-123, the following reactions are favored due to the absence of I-124 and I-125 impurities: 54124Xe(P,2n)55123Cs5.9minβ+54123Xe2.08hrβ+53123I54124Xe(P,pn)54123Xe2.08hrβ+53123I Recently in Cyclotron and Nuclear Medicine Department of NRCAM, at Atomic Energy organization of Iran (AEOI), a system for producing I-123 via Xe-124 gas target technology, has been constructed and installed. One of the major problems in this system is the highly expensive cost of the enriched Xenon-124 gas. Therefore, saving this gas inside the system is very important. Unfortunately, by accidental rupture of the window foil or bad function of O-rings, the whole Xenon gas will escape from the system immediately. In this paper, by using computer codes; ALICE91, SRIM and doing some calculations we are going to demonstrate our latest effort for feasibility study of producing I-123 with the above mentioned reactions, but using Xe-124 solid target instead. According to our suggested design, a conical shaped irradiation vessel made of copper with 1mm thickness, 1cm outlet diameter, 5cm length and 12° angle at summit can be fixed inside a liquid nitrogen housing chamber. The Xenon-124 gas will be sent to the inside of this very cold conical trap and eventually deposited on its surface in solid form. Our calculation shows that during bombardment with 17–28 MeV proton energy, the thickness of solidified Xenon layer will remain around .28 mm. Likewise; thermo-dynamical calculation shows that in order to prevent the evaporation of solidified Xenon, the maximum permissible proton beam current for this system should be less than 1.4 μA. According to these working conditions, the production yield of I-123 can be predicted to be around 150 mCi/μAh.