Letteratura scientifica selezionata sul tema "Lin, Li-Chin"

Four new genera and 11 new species of Hahniidae Bertkau, 1878 are described. The new genera are Goblinia Lin & Li, gen. nov., with the type species G. tiane Lin & Li, sp. nov. (♂♀) from Guangxi, China; Myahnia Lin & Li, gen. nov., with the type species M. kanpetlet Lin & Li, sp. nov. (♂♀) from Chin, Myanmar; Troglohnia Lin & Li, gen. nov., with the type species Tr. qiubei Lin & Li, sp. nov. (♂♀) from Yunnan, China and Typhlohnia Lin & Li, gen. nov., with the type species Ty. rongshui Lin & Li, sp. nov. (♂♀) from Guangxi, China. Seven additional new species are described: Tr. dafang Lin & Li, sp. nov. (♂♀) from Guizhou, China; Tr. shidian Lin & Li, sp. nov. (♀) from Yunnan, China; Tr. wuding Lin & Li, sp. nov. (♂♀) from Yunnan, China; Ty. banlaksao Lin & Li, sp. nov. (♀) from Bolikhamxay, Laos; Ty. kaiyang Lin & Li, sp. nov. (♀) from Guizhou, China; Ty. sondoong Lin & Li, sp. nov. (♂♀) from Quang Binh, Vietnam and Ty. suiyang Lin & Li, sp. nov. (♀) from Guizhou, China.

The isolated scattering number is a parameter that measures the vulnerability of networks. This measure is bounded by formulas depending on the independence number. We present new bounds on the isolated scattering number that can be calculated in polynomial time. References Z. Chen, M. Dehmer, F. Emmert-Streib, and Y. Shi. Modern and interdisciplinary problems in network science: A translational research perspective. CRC Press, 2018. doi: 10.1201/9781351237307 P. Erdős and T. Gallai. On the minimal number of vertices representing the edges of a graph. Magyar Tud. Akad. Mat. Kutató Int. Közl. 6 (1961), pp. 181–203. url: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.210.7468 J. Harant and I. Schiermeyer. On the independence number of a graph in terms of order and size. Discrete Math. 232.1–3 (2001), pp. 131–138. doi: 10.1016/S0012-365X(00)00298-3 E. Korach, T. Nguyen, and B. Peis. Subgraph characterization of red/blue-split graph and Kőnig Egerváry graphs. Proceedings of the Seventeenth Annual ACM-SIAM Symposium on Discrete Algorithms. ACM, New York, 2006, pp. 842–850. doi: 10.1145/1109557.1109650 F. Li, Q. Ye, and Y. Sun. Proceedings of the 2016 Joint Conference of ANZIAM and Zhejiang Provincial Applied Mathematics Association, ANZPAMS-2016. Ed. by P. Broadbridge, M. Nelson, D. Wang, and A. J. Roberts. Vol. 58. ANZIAM J. 2017, E81–E97. doi: 10.21914/anziamj.v58i0.10993 F. Li, Q. Ye, and X. Zhang. Isolated scattering number of split graphs and graph products. ANZIAM J. 58.3-4 (2017), pp. 350–358. doi: 10.1017/S1446181117000062 E. R. Scheinerman and D. H. Ullman. Fractional graph theory. Dover Publications, 2011. url: https://www.ams.jhu.edu/ers/wp-content/uploads/2015/12/fgt.pdf S. Y. Wang, Y. X. Yang, S. W. Lin, J. Li, and Z. M. Hu. The isolated scattering number of graphs. Acta Math. Sinica (Chin. Ser.) 54.5 (2011), pp. 861–874. url: http://www.actamath.com/EN/abstract/abstract21097.shtml M. Xiao and H. Nagamochi. Exact algorithms for maximum independent set. Inform. and Comput. 255, Part 1 (2017), pp. 126–146. doi: 10.1016/j.ic.2017.06.001

Abstract Ferroptosis is an iron-dependent oxidative cell death with accumulation of lipid peroxidation and abnormal morphology of mitochondria. Although previous studies have shown that ferroptosis inducers have therapeutic potentials in several treatment-naive and drug-resistant cancer types, lacking systematic analysis of the ferroptosis sensitivity in different cancer types makes it difficult to know which cancer type is suitable for clinical usage and critical regulator determining the ferroptosis sensitivity during cancer progression is still not clear. In this study, colon cancer was identified as one of the ferroptosis-insensitive cancer types by dry and wet bench analyses. Importantly, our large-scale analysis also showed that NUDT16L1 was a novel ferroptosis repressor and overexpressed in colon cancer clinical specimens. Similar findings are also observed in the chemical-induced and genetic mouse models of colon cancer. Furthermore, NUDT16L1 loss-of-function and gain-of-function cell models and its conditional knock-in and knock-out mouse models are used to prove its crucial role in the development of colon cancer. In addition, loss of NUDT16L1 induced several key ferroptosis characteristics and impairment of mitochondrial functions while its restoration attenuated those phenomena in colon cancer cells. Mechanistically, our RNA-Seq and RIP-Seq analyses shown that NUDT16L1 directly interacted and positively regulated several crucial negative regulators of ferroptosis. More interestingly, loss of NUDT16L1 not only restores the sensitivity of ferroptosis inducer but also impairs the function of mitochondria. Finally, a specific NUDT16L1 inhibitor was shown to not only repress colon cancer growth in vitro and in vivo but also induce the ferroptosis in colon cancer. In conclusion, this is the first study to demonstrate that overexpression of NUDT16L1 promotes colon cancer progression by inhibition of ferroptosis and maintenance proper function of mitochondria. Furthermore, specific NUDT16L1 inhibitor might be a promising therapeutic strategy for colon cancer patient in the future. Citation Format: Yi-Syuan Lin, Ya-Chuan Tsai, Chia-Jung Li, Tzu-Tang Wei, Ya-Na Wu, Shang-Rung Wu, Shin-Chin Lin, Shaw-Jenq Tsai, Shih-Chieh Lin. NUDT16L1 promotes colon cancer progression via inhibition of ferroptosis [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 1372.

Electrolytes in Li-ion batteries play a significant role as they influence different aspects directly related to the battery performance, such as safety, voltage window, electrochemical stability, and the formation of solid-electrolyte interphase (SEI). Conventionally, these electrolytes are composed of a lithium salt dissolved in an organic solvent such as ethylene carbonate and propylene carbonate. Regarding safety, these organic electrolytes can be replaced by room-temperature ionic liquids (RTILs), which present lower vapor pressure and non-flammability.1 Moreover, adding polymer to these liquid electrolytes to form polymer gel electrolytes has proven to be a good strategy to avoid dendritic growth and increase electrolyte stability.2 The properties of RTIL electrolytes containing Li salts have been studied in the last decade. Still, the scope has been limited primarily to simple RTILs consisting of one cationic and one anionic species. Inspired by the success of high-entropy alloys (HEAs) for forming stable solid solutions with excellent mechanical properties,3 the concept of high-entropy materials has been recently transferred to electrolytes, where the effect of mixing multiple Li salts is explored.4 However, the number of compositional combinations increases rapidly when multiple salts, cationic and anionic species are introduced, and the explorable compositional space increases even more when polymers are added to the mixture. Automating the electrolyte preparation and characterization can be the key feature to allow the exploration of all the possible electrolyte combinations. In this work, we explain the first preliminary results obtained from an autonomous preparation and characterization of high-entropy electrolytes composed of a mixture of two different lithium salts in ionic liquids consisting of multiple anionic and cationic species. In addition, the adaptation of the autonomous system of preparation and characterization of liquid electrolytes to polymer gel electrolytes is also proposed and explained. References. (1) Niu, H.; Wang, L.; Guan, P.; Zhang, N.; Yan, C.; Ding, M.; Guo, X.; Huang, T.; Hu, X. Recent Advances in Application of Ionic Liquids in Electrolyte of Lithium Ion Batteries. J. Energy Storage 2021, 40, 102659. https://doi.org/10.1016/j.est.2021.102659. (2) Chen, J.; Wu, J.; Wang, X.; Zhou, A.; Yang, Z. Research Progress and Application Prospect of Solid-State Electrolytes in Commercial Lithium-Ion Power Batteries. Energy Storage Mater. 2021, 35, 70–87. https://doi.org/10.1016/j.ensm.2020.11.017. (3) Yeh, J.-W.; Chen, S.-K.; Lin, S.-J.; Gan, J.-Y.; Chin, T.-S.; Shun, T.-T.; Tsau, C.-H.; Chang, S.-Y. Nanostructured High-Entropy Alloys with Multiple Principal Elements: Novel Alloy Design Concepts and Outcomes. Adv. Eng. Mater. 2004, 6 (5), 299–303. https://doi.org/10.1002/adem.200300567. (4) Wang, Q.; Zhao, C.; Wang, J.; Yao, Z.; Wang, S.; Kumar, S. G. H.; Ganapathy, S.; Eustace, S.; Bai, X.; Li, B.; Wagemaker, M. High Entropy Liquid Electrolytes for Lithium Batteries. Nat. Commun. 2023, 14 (1), 440. https://doi.org/10.1038/s41467-023-36075-1.

Abstract It is reported that long-term use of estrogen could increase the risk of ovarian cancer. However, the role of estrogen in immunoevasion is not fully explored. We have previously demonstrated that estrogen-mediated upregulation of E2F6, and, c-Kit, by epigenetic silencing of miR-193a, and a competing endogenous (ceRNA) mechanism. In this study, we found that PBX1, a transcriptional activator of the immunosuppressive cytokine, IL-10, is also a target of miR-193a. Importantly, overexpression of the E2F6 3’UTR upregulates both E2F6 and, PBX1, as well as IL10 in ovarian cancer cell lines, suggesting that ceRNA mechanism exists between E2F6 and PBX1. These phenomena are further supported by our stochastic simulation of the estrogen-mediated E2F6 ceRNA network on the distribution of E2F6 and PBX1 mRNA in cancer cells, which is consistent with the TCGA ovarian cancer RNA-Seq dataset. Importantly, monocyte-derived dendritic cell activation of T-cell function was inhibited by pretreatment of conditioned media derived from ovarian cancer cells overexpressing E2F6 3’UTR; such inhibition was rescueable by an anti-IL-10 antibody. Clinically, IL10 level was higher in ovarian cancer patients with higher E2F6 and PBX1, and in ovarian cancer cell lines overexpressed with E2F6 3’UTR. Taken together, these results showed that E2F6 could suppress anti-tumor immune response of dendritic cell, E2F6 ceRNA network. Epigenetic intervention in restoring the expression of miR-193a may be able to enhance anti-tumor immune response against ovarian cancer. Citation Format: Michael W.Y. Chan, Yin-Chen Chen, Ching-Wen Lin, Frank Cheng, Ching-Cher Sanders Yan, Chao-Ping Hsu, Yu-Min Chuang, Jie-Ting Low, Xiaojing Ma, Yao-Ting Huang, Chia-Bin Chang, Chin Li, Hung-Cheng Lai, Shu-Fen Wu, Shih-Hsun Hung, Je-Chiang Tsai. A E2F6 ceRNA network suppresses dendritic cell function, via PBX1/IL-10 signaling, in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 97.

Abstract Twenty-one gliomas in patients aged 0-21 years were evaluated for drug sensitivity by ex vivo expanded circulating tumor cells (CTC). The results were correlated with clinical outcomes. Venous blood samples were obtained prior to drug treatment. Peripheral blood mononuclear cells were processed in a 3D cell culture system (EVA Select™, Cancer Free Biotech Ltd., Taipei, Taiwan) and cultured for 3 weeks. Expanded CTCs were successfully cultured into organoids from 18 out of 21 patients and were analyzed for ATP abundance. Staining with CD45, a marker for blood cells, and pancytokeratin, a marker for keratinocytes, was performed on the cultured cells. Staining of GFAP, a marker of glioma cells, was performed in a subset of samples. These cells were then tested in cytotoxicity assays in triplicate with a panel of chemotherapeutic and targeted agents at clinically relevant concentrations. The surviving fraction was normalized to a buffer-only control. Based on the percentage of cell viability, the agent was chosen for clinical treatment. Comparing the results among low-grade glioma (LGG; n = 6), diffuse midline glioma (DMG; n = 4), and high-grade glioma (HGG, n = 8; including glioblastoma multiforme [GBM; n = 5]), the mean surviving fraction to temozolomide was similarly high across the three tumor types (LGG vs. DMG vs. HGG = 57.5% vs. 50.6% vs. 49.5%, respectively). 6 of 6 patients in the LGG group showed CTC sensitivity to at least one chemotherapeutic agent tested. The clinical response of patients treated with selected agents was evaluated with the RANO criteria at 6 months after initiation of treatment. Among the 24 agents tested with clinical correlation, the CTC surviving fraction after exposure to the agent was significantly higher in patients who had progressive disease within 6 months (n = 11; 68%) vs. in patients with no progression at 6 months (n = 13; 39%; P = 0.039). Treating CTCs with histone deacetylase inhibitors in vitro resulted in a consistently lower surviving fraction (15.1% ± 12.0%) for DMG and HGG/GBM; however, clinical correlation was not available. The 1 patient with clinical correlation with HGG had a 34.9% surviving fraction to a Tyrosine kinase inhibitor (TKI) in vitro and showed a 42.9% shrinkage at 6 months after treatment with the TKI. The expansion of CTCs in patients with relapsed/refractory pediatric gliomas provides the ability to test drug sensitivity of patient-derived organoids. Our data suggest a correlation between the ex vivo drug sensitivity of CTCs and clinical response. Citation Format: Yen-Lin Liu, Yin-Ju Chen, Shu-Huey Chen, Yu-Mei Liao, Wu Shih-Pei, Yi-Hsuan Chen, Wan-Ling Ho, Liang-Yi Juo, Chia-Yau Chang, Jinn-Li Wang, Min-Yu Su, Pei-Chin Lin, Shih-Chung Wang, James S. Miser, Tai-Tong Wong, Yuan-Hung Wu, Peng Yuan Wang, Thierry Burnouf, Jeng-Fong Chiou, Long-Sheng Lu. Application of in vitro drug screening of circulating tumor cells in pediatric glioma therapy. [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 6723.

Abstract Cancer cells need metabolic adaptations to survive in hostile environment such as low nutrient and drug treatment conditions. DLBCLs (Diffuse large B cell lymphoma) originate from a metabolic competitive/challenging environment of germinal center (GC) when B cells undergo positive selections against antigens. However, it is largely unknown whether and how metabolic flexibility (the ability to use different nutrients) and plasticity (the ability to process the same nutrient differently) contribute to DLBCLs. Our previous study identified that SIRT3, the only mitochondrial protein deacetylase, is critical to survival and proliferation of DLBCLs by promoting glutaminolysis. Our mitochondrial localized SIRT3 inhibitor, YC8-02, has pan-toxicity to all DLBCL cells tested regardless of different subtypes with somatic mutations. Here, we observed glucose as an alternative nutrient source to compensate in the TCA cycle in SIRT3 deficient cells. DLBCLs exhibited resistance to SIRT3 inhibition in high glucose condition, while SIRT3 inhibited DLBCLs highly depend on glucose metabolism. The combination of YC8-02 with glucose metabolism inhibitors induces synergistic killing to DLBCLs. As glucose is the main carbon source of cells, it is unknown how DLBCLs manage the flexibility of using glucose for different purposes. Using in vivo metabolic imaging (MALDI), we observed that, in contrast to normal GC B cells, lymphomas specifically use the glucose for de novo nucleotide synthesis. SIRT3 inhibition decreased nucleotide levels in DLBCL cells in vitro and in vivo. The metabolic flux tracing showed that DLBCL cells requires SIRT3 activity to activate a glucose/serine/one-carbon metabolism pathway for de novo nucleotide biosynthesis, and Inhibition of SIRT3 decreased the glucose and serine being used for nucleotides in DLBCLs. Serine as another potent source for nucleotides can rescue DLBCLs from SIRT3 inhibition. Furthermore, we validated that overexpression of enzymes, like MTHFD2, in one carbon metabolism pathway can rescue the proliferation in SIRT3 deficient cells. High nucleotides levels in medium also help DLBCLs survival in YC8-02 treatments. To overcome the metabolic flexibility on environmental nucleotides, we used inhibitors of nucleoside transporters (ENT1/2), dipyridamole and draflazine, which can synergize with YC8-02 to kill DLBCLs in vitro and eradicate systemic lymphomas in vivo. In summary, our results illustrate that DLBCLs with active SIRT3 exhibit metabolic plasticity by repurposing glucose to nucleotide biosynthesis, while lymphoma cells can also reply on metabolic flexibility to manage nutrient usage and gain extracellular nucleotides for survival under SIRT3 inhibition. Our combination treatment SIRT3 and ENT inhibitors can be a promising therapy for DLBCLs by restraining their metabolic plasticity and flexibility. Citation Format: Meng Li, Noel R Park, Chris Chin, Coraline Mlynarczyk, Hening Lin, Shawn Davidson, Ari M Melnick. Targeting metabolic plasticity and flexibility via SIRT3 inhibition to restrain nucleotides availability in DLBCLs [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-034.

Introdução: A COVID-19 tornou-se uma emergência de saúde pública no ano de 2020, sendo caracterizada como pandemia no mês de março. Os idosos compõem o grupo de risco dessa doença. Objetivo: Avaliar os efeitos da pandemia de COVID-19 sobre os idosos. Material e Método: A busca pelos artigos foi realizada através da plataforma Pubmed, com a inclusão de 17 estudos. Resultados: Os resultados ressaltaram a prevalência da doença entre a população idosa, e evidenciaram que esse grupo apresenta sintomas atípicos e com duração ligeiramente mais longa desde o início da sintomatologia até a sua admissão, tornando-se mais difícil a identificação da infecção de forma precoce. As manifestações clínicas mais relatadas foram: febre, tosse, produção de escarro, diarreia, fadiga, pneumonia e lesão cardíaca aguda. Também se observa que comorbidades, como hipertensão e doença pulmonar obstrutiva crônica, levam a uma disfunção cardíaca e pulmonar devido a mudanças fisiológicas e anatômicas dos pulmões, agravando o quadro clínico dos pacientes. Os exames de imagem se mostraram grandes aliados ao diagnóstico das alterações pulmonares decorrentes da infecção, além da realização do exame RT-PCR. Conclusão: Os idosos compõem o grupo de risco da COVID-19, sendo indivíduos com comorbidades os mais susceptíveis à agravamentos clínicos. Há necessidades em seguir as recomendações da OMS por não haver um tratamento específico destinado a essa patologia. Descritores: Infecções por Coronavírus; Idoso; Diagnóstico Clínico. Referências World Health Organization [homepage internet]. Pandemia de doença por coronavirus (COVID-19) [acesso em 19 nov 2020]. Disponível em: http: https://www.who.int/emergencies/diseases/novel-coronavirus-2019?gclid=CjwKCAiAzN j9BRBDEiwAPsL0d-MtvP29HNfG_fKThMRyfZF5ZAhTrrwKXEDh74AOZlY7ddRjJ_su0 hoCK3EQAvD_BwE. Organização Pan-Americana de Saúde [homepage na internet]. Folha informativa COVID-19 - Escritório da OPAS e da OMS no Brasil [acesso em: 19 nov. 2020]. Disponível em: https://www.paho.org/pt/covid19. Ministério da Saúde [homepage na internet]. Painel Coronavirus Brasil [acesso em: 19 nov. 2020]. Disponível em: http:https://covid.saude.gov.br/. Liu K, Zhang W, Yang Y, Zhang J, Li Y, Chen Y. Respiratory rehabilitation in elderly patients with COVID-19: A randomized controlled study. Complement The Clin Pract. 2020:101166. Lee JY, Kim HA, Huh K, Hyun M, Rhee J-Y, Jang S, et al. Risk Factors for Mortality and Respiratory Support in Elderly Patients Hospitalized with COVID-19 in Korea. J Korean Med Sci. 2020;35(23) Nikpouraghdam M, Farahani AJ, Alishiri G, Heydari S, Ebrahimnia M, Samadinia H, et al. Epidemiological characteristics of coronavirus disease 2019 (COVID-19) patients in IRAN: A single center study. J Clin Virol. 2020; 127:104378. Zheng Y, Xu H, Yang M, Zeng Y, Chen H, Liu R, et al. Epidemiological characteristics and clinical features of 32 critical and 67 noncritical cases of COVID-19 in Chengdu. J Clin Virol. 2020;127:104366. Porcheddu R, Serra C, Kelvin D, Kelvin N, Rubino S. Similarity in case fatality rates (CFR) of COVID-19/SARS-COV-2 in Italy and China. J Infect Dev Ctries. 2020;14(02):125-8. Buckner FS, McCulloch DJ, Atluri V, Blain M, McGuffin SA, Nalla AK, et al. Clinical Features and Outcomes of 105 Hospitalized patients with COVID-19 in Seattle, Washington. Clin Infect Dis. 2020;71(16):2167-73. Liu K, Fang Y-Y, Deng Y, Liu W, Wang M-F, Ma J-P, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J. 2020;133(9):1025-31. Zhao M, Wang M, Zhang J, Gu J, Zhang P, Xu Y, et al. Comparison of clinical characteristics and outcomes of patients with coronavirus disease 2019 at different ages. Aging (Albany NY). 2020;12(11):10070. Wang L, He W, Yu X, Hu D, Bao M, Liu H, et al. Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up. J Infect. 2020;80(6):639-45. Guo T, Shen Q, Guo W, He W, Li J, Zhang Y, et al. Clinical Characteristics of Elderly Patients with COVID-19 in Hunan Province, China: A Multicenter, Retrospective Study. Gerontol. 2020:1-9. Ward CF, Figiel GS, McDonald WM. Altered Mental Status as a Novel Initial Clinical Presentation for COVID-19 Infection in the Am J Geriatr Psychiatry. 2020;28(8):808-11. Liu K, Chen Y, Lin R, Han K. Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients. J Infect. 2020;80(6):e-14-8. Li T, Zhang Y, Gong C, Wang J, Liu B, Shi L, et al. Prevalence of malnutrition and analysis of related factors in elderly patients with COVID-19 in Wuhan, China. Eur J Clin Nutr. 2020:1-5. Niu S, Tian S, Lou J, Kang X, Zhang L, Lian H, et al. Clinical characteristics of older patients infected with COVID-19: A descriptive study. Arch Gerontol Geriatr. 2020;89:104058. Fatyga E, Dzięgielewska-Gęsiak S, Wierzgoń A, Stołtny D, Muc-Wierzgoń M. The coronavirus disease 2019 pandemic: telemedicine in elderly patients with type 2 diabetes. Pol Arch int Med. 2020;130(5):452-54. Li P, Chen L, Liu Z, Pan J, Zhou D, Wang H, et al. Clinical Features and Short-term Outcomes of Elderly Patients With COVID-19. Int J Infect Dis. 2020;97:245-50. Kumar A, Kubota Y, Chernov M, Kasuya H. Potential Role of Zinc Supplementation in Prophylaxis and Treatment of COVID-19. Med Hypotheses. 2020;144:109848.

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. 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