101 research outputs found

    Power Fiber to the Home Opens Up a New Approach of Integration of Three Networks

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    AbstractThis thesis analyzes the development trend of power fiber to the home (PFTTH) and the current domestic situation of the integration of three networks. It develops its research about the integration system constitution of three networks based on power fiber to the home and proposes the research, development and implementation of power fiber to the home, which not only establishes new “information highway” based on the smart power grid, but also guarantees the realization of the state's planning objective of the integration of three networks to enable the rapid development of information industry in Chin

    The effects of low levels of aflatoxin B1 on health, growth performance and reproductivity in male rabbits

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    [EN] This study investigated the chronic effects of relatively low exposure to aflatoxin B1 (AFB1) on the growth performance, immune situation and reproduction in male rabbits. Bucks (n=32, 4.82±0.22 kg) were individually assigned to 4 treatments (8 replicates each) using a randomised complete block design. Four diets containing 0, 0.02, 0.05, and 0.1 mg AFB1/kg, were provided to bucks for 8 wk. Growth performance and semen quality were measured. Blood, organ and tissue samples were collected to measure haematological indices, liver function, organ weights and immune parameters. Compared to control, AFB1-contaminated diets reduced body weight and average daily gain (P<0.05), altered certain haematological indices and liver function with decreased monocytes percentage and mean corpuscular haemoglobin concentration, and increased plateletcrit and albumin (P<0.05), slightly impaired reproductive parameters with enhanced ratio of morphologically abnormal sperm cells at early stage and reduced post-stage acrosome integrity, testis weight and serum testosterone concentration (P<0.05), decreased immune function with reduced relative liver weight (%) and tumour necrosis factor-α levels in serum and liver tissue, and increased serum 8-hydroxy-2’-deoxyguanosine levels (P<0.05). Furthermore, bucks fed diets with relatively high AFB1 (0.05 and 0.1 mg AFB1/kg) had reduced red blood cell and haematocrit (P<0.05) in contrast with the low AFB1 group (0.02 mg AFB1/kg). In conclusion, diets containing 0.05 and 0.1 mg AFB1/kg had negative effects on bucks’ growth performance, haematology, reproductivity and immune function, whereas diet containing 0.02 mg AFB1/kg had only minor effects on the parameters measured.The study was funded by the Fundamental Research Funds for the Central Universities (XDJK2015C081).Sun, Y.; Dong, G.; E, G.; Liao, M.; Tao, L.; Lv, J. (2018). The effects of low levels of aflatoxin B1 on health, growth performance and reproductivity in male rabbits. World Rabbit Science. 26(2):123-133. https://doi.org/10.4995/wrs.2018.7433SWORD123133262Abdelaziz S.A., Hamada M.M. 2007. Phytic acid exposure alters AflatoxinB1-induced reproductive and oxidative toxicity in Albino Rats (Rattus norvegicus). eCAM, 6: 331-3471. https://doi.org/10.1093/ecam/nem137Abdel-Wahhab M.A., Nada S.A., Khalil F.A.2002. Physiological and toxicological responses in rats fed aflatoxin-contaminated diet with or without sorbent materials. Animal Feed Sci. Tech., 97: 209-219. https://doi.org/10.1016/S0377-8401(01)00342-XAbnet C.C. 2007.Carcinogenic food contaminants. Cancer Invest., 25: 189-196. https://doi.org/10.1080/07357900701208733Adedara I.A., Nanjappa M.K., Farombi E.O., Akingbemi B.T. 2014. Aflatoxin B1 disrupts the androgen biosynthetic pathway in rat Leydig cells. Food Chem. Toxicol., 65: 252-259. https://doi.org/10.1016/j.fct.2013.12.027Alm K., Dahlbom M., Saynajarvi M., Anderson M.A., Salkinoja-Salonen M.S., Anderson M.C. 2002. Impaired semen quality of AI bulls fed with moldy hay: a case report. Theriogenology, 58: 1497-1502. https://doi.org/10.1016/S0093-691X(02)01079-8Asare G.A., Bronz M., Naidoo V., Kew M.C. 2007. Interactions between aflatoxin B1 and dietary iron overload in hepatic mutagenesis. Toxicol., 234: 157-166. https://doi.org/10.1016/j.tox.2007.02.009Ataman M.B., Dönmez H.H., Dönmez N., Sur E., Bucak M.N., Çoyan, K. 2014. Protective effect of esterified glucomannan on aflatoxin-induced changes in testicular function, sperm quality, and seminal plasma biochemistry in rams. Theriogenology, 81: 373-380. https://doi.org/10.1016/j.theriogenology.2013.10.007Clarke R.N., Doerr J.A., Ottinger M.A. 1986. Relative importance of dietary aflatoxin and feed restriction on reproductive changes associated with aflatoxicosis in the maturing white leghorn male. Poul. Sci., 65: 2239-2245. https://doi.org/10.3382/ps.0652239Cotty P.J., Jaime-Garcia R. 2007. Influences of climate on aflatoxin producing fungi and aflatoxin contamination. Int. J. Food Microbiol., 199: 109-115. https://doi.org/10.1016/j.ijfoodmicro.2007.07.060David S.S., O'Shea V.L., Kundu S. 2007. Base-excision repair of oxidative DNA damage. Nature, 447: 941-950. https://doi.org/10.1038/nature05978Dönmez N., Keskin E. 2008. The effects of aflatoxin and glucomannan on some antioxidants and biochemical parameters in rabbits. Acta Vet. Beograd., 58: 307-313. https://doi.org/10.2298/AVB0804307DEgbunike G.N. 1982. Steroidogenic and spermatogenic potentials of the male rat after acute treatment with Aflatoxin B1. Andrologia, 14: 440-446. https://doi.org/10.1111/j.1439-0272.1982.tb02291.xEisa A.M.A., Metwally A.Y. 2011. Effect of glucomannan on haematological, coagulation and biochemical parameters in male rabbits fed aflatoxin-contaminated ration. World Mycotoxin J., 4: 183-188. https://doi.org/10.3920/WMJ2010.1273Ellis O., Smith J.P., Simpson B.K. 1991. Aflatoxins in food: occurrence, biosynthesis, effects on organisms, detection, and methods of control. Crit. Rev. Food. Sci., 30: 403-439. https://doi.org/10.1080/10408399109527551European Commission. 2003. Commission directive 2003/100/EC of 31 October 2003 amending Annex I to Directive 2002/32/EC of the European Parliament and of the Council on undesirable substances in animal feed. No. 2003/100/EC, 31 October 2003. Off. J. Eur. Comm., 1 November 2003, L 285, 33-37.Ewuola E.O. 2008. Organ traits and histopathology of rabbits fed varied levels of dietary fumonisin B1. J. Anim. Physiol. An. N., 93: 726-731. https://doi.org/10.1111/j.1439-0396.2008.00862.xEwuola E.O., Egbunike G.N. 2010. Effects of dietary fumonisin B1 on the onset of puberty, semen quality, fertility rates and testicular morphology in male rabbits. Reproduction, 139: 439-445. https://doi.org/10.1530/REP-09-0077Ewuola E.O., Jimoh O.A., Bello A.D., Bolarinwa A.O. 2014. Testicular biochemicals, sperm reserves and daily sperm production of West African dwarf bucks fed varied levels of dietary aflatoxin. Anim. Reprod. Sci., 148: 182-187. https://doi.org/10.1016/j.anireprosci.2014.05.010Fan Y., Li X., Zhao L., Jia Y., Ji C., Ma Q., Chen Y., Wang L. 2012. Investigation on contamination situation of aflatoxin in detected feeds and feedstuffs in Beijing area. Scientia Agricultura Sinica, 45: 5102-5109.Fan Y., Zhao L., Ma Q., Li X., Shi H., Zhou T., Zhang J., Ji C. 2013. Effects of Bacillus subtilis ANSB060 on growth performance, meat quality and aflatoxin residues in broilers fed moldy peanut meal naturally contaminated with aflatoxins. Food Chem. Toxicol., 59: 748-753. https://doi.org/10.1016/j.fct.2013.07.010Faridha A., Faisal K., Akbarsha M.A. 2006. Duration-dependent histopathological and histometric changes in the testis of aflatoxin-treated mice. J. Endocrin. Reprod., 10: 117-133.Gholami-Ahangaran M., Zia-Jahromi N. 2013. Nanosilver effects on growth parameters in experimental aflatoxicosis in broiler chickens. Toxicol. Ind. Health, 29: 121-125. https://doi.org/10.1177/0748233711425078Gong Y., Hounsa A., Egal S., Turner P.C., Sutcliffe A.E., Hall A.J., Cardwell K., Wild C.P. 2004. Post-weaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin. Environ. Health Perspect., 112: 1334-1338. https://doi.org/10.1289/ehp.6954Guerre P., Eeckhoutte C., Larrieu G., Burgat V., Galtier P. 1996. Dose-related effect of aflatoxin B1 on liver drug metabolizing enzymes in rabbit. Toxicology, 108: 39-48.https://doi.org/10.1016/S0300-483X(95)03269-LGuerre P., Larrieu G., Burgat V., Galtier P. 1999. Cytochrome P450 decreases are correlated to increased microsomal oxidative damage in rabbit liver and primary cultures of rabbit hepatocytes exposed to AFB1. Toxicol. Lett., 104: 117-125.https://doi.org/10.1016/S0378-4274(98)00352-XGuindon-Kezis K.A., Mulder J.E., Massey T.E. 2014. In vivo treatment with aflatoxin B1 increases DNA oxidation, base excision repair activity and 8-oxoguanine DNA glycosylase 1 levels in mouse lung. Toxicology, 321: 21-26. https://doi.org/10.1016/j.tox.2014.03.004Hancock K.D., Coleman E.S., Tao Y.X., Morrison E.E., Braden T.D., Kemppainen B.W., Akingbemi B.T. 2009. Genistein decreases androgen biosynthesis in rat Leydig cells by interference with luteinizing hormone-dependent signaling. Toxicol. Lett., 184: 169-175. https://doi.org/10.1016/j.toxlet.2008.11.005Issac A.A., Manjunatha K.N., Ebenezer O.F., Benson T.A. 2014. Aflatoxin B1 disrupts the androgen biosynthetic pathway in rat Leydig cells. Food Chem. Toxicol., 65: 252-259. https://doi.org/10.1016/j.fct.2013.12.027Kaneko J.J., Harvey J.W., Bruss M. 1997. Serum protein and the dysproteinemias. In clinical biochemistry of domestic animals, 5th ed.; Academic press: San Diego, CA, USA; pp. 117-137. https://doi.org/10.1016/B978-012396305-5/50006-3Kärenlampi S.O. 1987. Mechanism of cytotoxicity of aflatoxin B1: role of cytochrome P1-450. Biochem. Bioph. Res. Co., 145: 845-860. https://doi.org/10.1016/0006-291X(87)91043-6Kecici T., Demet Ö., Oguz H. 1995. Single and combined effects of dietary aflatoxin and adsorbent (Mycofix plus) on some hematological and serum biochemical parameters of broiler chickens. J. Vet. Sci., 11: 95-101.Kovács M., Tornyos G., Matics Zs., Kametler L., Rajli V., Bodnár Zs., Kulcsár M., Huszenicza Gy., Keresztes Zs., Cseh S. 2011. Subsequent effect of subacute T-2 toxicosis on spermatozoa, seminal plasma and testosterone production in rabbits. Animal, 5: 1563-1569. https://doi.org/10.1017/S1751731111000644Manafi M., Murthy H.N.N., Mohan K., Narayana H.D.S. 2012. Evaluation of different mycotoxin binders on broiler breeders induced with aflatoxin B1: effects on fertility, hatchability, embryonic mortality, residues in egg and semen quality. Global Vet., 8: 643-648.Marin D.E., TaranuI., Bunaciu R.P., Pascale F., Tudor D.S., Avram N., Sarca M., Cureu I., Criste R.D., Suta V., Oswald I.P. 2002. Changes in performance, blood parameters, humoral and cellular immune responses in weanling piglets exposed to low doses of aflatoxin. J. Anim. Sci., 80: 1250-1257. https://doi.org/10.2527/2002.8051250xMohanamba T., Rao M.R., Habibi S.M.M. 2007. Aflatoxin contamination in animal feeds. Ind. Vet. J., 84:416.3Morton D. 1988. The use of rabbits in male reproductive toxicology. Environ. Health Persp., 77: 5-9. https://doi.org/10.1289/ehp.88775Oguz H., Kurtoglu V. 2000. Effect of clinoptilolite on performance of broiler chickens during experimental aflatoxicosis. Brit. Poult. Sci., 41: 512-517. https://doi.org/10.1080/713654953Peters L.P., Teel R.W. 2003. Effect of high sucrose diet on liver enzyme content and activity and aflatoxin B1-induced mutagenesis. InVivo.,17: 205-210.Prabu P.C., Dwivedi P., Sharma A.K. 2013. Toxico pathological studies on the effects of aflatoxin B1, ochratoxin A and their interaction in New Zealand White rabbits. Exp. Toxicol. Pathol., 65: 277-286. https://doi.org/10.1016/j.etp.2011.09.003Richard J.L., Thurston J.R. 1975. Effect of aflatoxin on phagocytosis of Aspergillus fumigatus spores by rabbit alveolar macrophages. Appl. Microbiol., 30: 44-47.Rustemeyer S.M., Lamberson W.R., Ledoux D.R., Rottinghaus G.E., Shaw D.P., Cockrum R.R., Kessler K.L., Austin K.J., Cammack K.M. 2014. Effects of dietary aflatoxin on the health and performance of growing barrows. J. Anim. Sci., 88: 3624-3630.https://doi.org/10.2527/jas.2009-2663Salem M.H., Kamel K.I., Yousef M.I., Hassan G.A., ELNouty F.D. 2001. Protective role of ascorbic acid to enhance semen quality of rabbits treated with sublethal doses of aflatoxin B1. Toxicology, 162: 209-218.https://doi.org/10.1016/S0300-483X(01)00366-3Sherrill J.D., Sparks M., Dennis J., Mansour M., Kemppainen B.W., Bartol F.F., Morrison E.E., Akingbemi B.T. 2010. Developmental exposures of male rats to soy isoflavones impact Leydig cell differentiation. Biol. Reprod., 83: 488-501. https://doi.org/10.1095/biolreprod.109.082685Soliman K.M., El-Faramawy A.A., Zakaria S.M., Mekkawy S.H. 2001. Monitoring the preventive effect of hydrogen peroxide and γ-radiation of aflatoxicosis in growing rabbits and the effect of cooking on aflatoxin residues. J. Agric. Food Chem., 49: 3291-3295. https://doi.org/10.1021/jf0010735Tung H.T., Donaldson W.E., Hamilton P.B. 1972. Altered lipid transport during aflatoxicosis. Toxicol. Appl. Pharmacol., 22: 97-104. https://doi.org/10.1016/0041-008X(72)90229-3Verma R.J., Mathuria N. 2010. Curcumin ameliorates aflatoxininduced changes in caput and cauda epididymis of mice. Int. J. Fertil. Steril., 4: 17-22.Waal Malefyt R., Abrams J., Bennett B., Figdor C.G., de Vries J.E. 1991. Interleukin 10 (IL-10) inhibits cytokine synthesis: An auto regulatory role of IL-10 produced by monocytes. J. Exp. Med. 174: 1209-1220. https://doi.org/10.1084/jem.174.5.1209Weaver A.C., See M.T., Hansen J.A., Kim Y.B, De Souza A.L.P., Teena F.M., Kim S.W. 2013. The use of feed additives to reduce the effects of aflatoxin and deoxynivalenol on pig growth, organ health and immune status during chronic exposure. Toxins, 5: 1261-1281. https://doi.org/10.3390/toxins5071261Williams J.H., Phillips T.D., Jolly P.E., Stiles J.K., Jolly C.M. Aggarwal D. 2004. Human aflatoxicosis in developing countries; a review of toxicology, exposure, potential health consequences, and interventions. Am. J. Clin. Nutr., 80: 1106-1122. https://doi.org/10.1093/ajcn/80.5.1106Yang J., Bai F., Zhang K., Bai S., Peng X., Ding X., Li Y., Zhang J., Zhao L. 2012. Effects of feeding corn naturally contaminated with aflatoxin B1 and B2 on hepatic functions of broilers. Poul. Sci., 91: 2792-2801. https://doi.org/10.3382/ps.2012-02544Yegani M., Smith T.K., Leeson S., Boermans H.J. 2006. Effects of feeding grains naturally contaminated with Fusarium mycotoxins on performance and metabolism of broiler breeders. Poult. Sci., 85: 1541-1549. https://doi.org/10.1093/ps/85.9.1541Yu F.L. 1982. Studies on the mechanism of aflatoxin B1 inhibition of the rat liver nucleolar RNA synthesis. J. Biol. Chem., 256: 3292-3297.Yunus A.W., Razzazi-Fazeli E., Bohm J. 2011. Aflatoxin B1 in affecting broiler's performance, immunity, and gastrointestinal tract: a review of history and contemporary issues. Toxins, 3: 566-590. https://doi.org/10.3390/toxins306056

    Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells

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    Purpose: Slow transit constipation (STC) is a common gastrointestinal disorder characterized by altered gut microbiota and reduced number of enterochromaffin cells (ECs). Astragaloside IV (AS-IV), a low drug permeability saponin, has showed beneficial effects on patients with STC. However, the specific mechanism by which AS-IV regulates STC remains unclear. In this study, we aimed to investigate the effect of AS-IV on STC and its associated mechanisms involving gut microbiota.Methods: The effect of AS-IV on STC was evaluated on STC mice induced with loperamide. We measured defecation frequency, intestinal mobility, ECs loss, and colonic lesions in STC mice treated with AS-IV. We also analyzed the changes in gut microbiota and metabolites after AS-IV treatment. Moreover, we investigated the relationship between specific gut microbes and altered fecal metabolites, such as 3-bromotyrosine (3-BrY). We also conducted in vitro experiments to investigate the effect of 3-BrY on caspase-dependent apoptosis of ECs and the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.Results: AS-IV treatment promoted defecation, improved intestinal mobility, suppressed ECs loss, and alleviated colonic lesions in STC mice. AS-IV treatment also affected gut microbiota and metabolites, with a significant correlation between specific gut microbes and altered fecal metabolites such as 3-BrY. Furthermore, 3-BrY may potentially reduce caspase-dependent apoptosis of ECs and protect cell survival by inhibiting the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.Conclusion: Our findings suggest that changes in gut microbiota and ECs mediated the therapeutic effect of STC by AS-IV. These results provide a basis for the use of AS-IV as a prebiotic agent for treating STC. The specific mechanism by which AS-IV regulates gut microbiota and ECs warrants further investigation

    Sacral terminal filar cyst: a distinct variant of spinal meningeal cyst and midterm clinical outcome following combination resection surgery

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    ObjectiveSpinal meningeal cysts (SMCs) are currently classified into three types: extradural cysts without nerve root fibers (Type I), extradural cysts with nerve root fibers (Type II), and intradural cysts (Type III). However, the sacral terminal filar cyst is a distinct subtype with the filum terminale rather than nerve roots within the cyst. This study aimed to investigate the clinicoradiological characteristics and surgical outcomes of sacral terminal filar cysts.MethodsA total of 32 patients with sacral terminal filar cysts were enrolled. Clinical and radiological profiles were collected. All patients were surgically treated, and preoperative and follow-up neurological functions were evaluated.ResultsChronic lumbosacral pain and sphincter dysfunctions were the most common symptoms. On MRI, the filum terminale could be identified within the cyst in all cases, and low-lying conus medullaris was found in 23 (71.9%) cases. The filum terminale was dissociated and cut off in all cases, and the cyst wall was completely resected in 23 (71.9%) cases. After a median follow-up period of 26.5 ± 15.5 months, the pain and sphincter dysfunctions were significantly improved (both P &lt; 0.0001). The cyst recurrence was noted in only 1 (3.1%) case.ConclusionsSacral terminal filar cysts are rare, representing a distinct variant of SMCs. Typical MRI features, including filum terminale within the cyst and low-lying conus medullaris, may suggest the diagnosis. Although the optimal surgical strategy remains unclear, we recommend a combination of resection of the cyst wall and dissociation of the filum terminale. The clinical outcomes can be favorable

    Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation

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    The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and aberrant functions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARÎł). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naĂŻve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV

    A 10-Year Retrospective Analysis of Clinical Profiles, Laboratory Characteristics and Management of Pyogenic Liver Abscesses in a Chinese Hospital

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    Ticagrelor vs Clopidogrel in CYP2C19 loss-of-function carriers with Stroke or TIA

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    BACKGROUNDComparisons between ticagrelor- aspirin and clopidogrel-aspirin in CYP2C19 loss-of-function carriers have not been well studied for secondary stroke prevention.METHODSWe conducted a randomized, double-blind, placebo-controlled trial of 6,412 patients with a minor ischemic stroke or TIA who carried CYP2C19 LOF alleles determined by point-of-care testing. Patients were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio to receive ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or clopidogrel (300 mg loading dose on day 1 followed by 75 mg per day for days 2 through 90), plus aspirin (75-300 mg loading dose followed by 75 mg daily for 21 days). The primary efficacy outcome was stroke and the primary safety outcome was severe or moderate bleeding, both within 90 days. RESULTSStroke occurred within 90 days in 191 (6.0%) versus 243 (7.6%), respectively (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P=0.008). Moderate or severe bleeding occurred in 9 patients (0.3%) in the ticagrelor-aspirin group and in 11 patients (0.3%) in the clopidogrel-aspirin group; any bleeding event occurred in 170 patients (5.3%) vs 80 (2.5%), respectively. CONCLUSIONSAmong Chinese patients with minor ischemic stroke or TIA within 24 hours after symptoms onset who were carriers of CYP2C19 loss-of-function alleles, ticagrelor- aspirin was modestly better than clopidogrel-aspirin for reducing the risk of stroke but was associated with more total bleeding events at 90 days. (CHANCE-2 ClinicalTrials.gov number, NCT04078737.

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Percutaneous Endoscopic Necrosectomy (PEN) Combined with Percutaneous Catheter Drainage (PCD) and Irrigation for the Treatment of Clinically Relevant Pancreatic Fistula after Pancreatoduodenectomy

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    Purpose: This study aimed to evaluate the efficacy of percutaneous endoscopic necrosectomy (PEN) combined with percutaneous catheter drainage (PCD) and irrigation versus PCD for the treatment of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). Materials and Methods: A total of 34 consecutive patients who suffered from CR-POPF after PD were enrolled in this retrospective cohort study. 12 patients received PEN combined with PCD and irrigation, and 22 patients received PCD. The complications and outcomes of the treatments were compared. Results: No patients suffered from severe PCD- or PEN-related complications. Compared with those treated with PCD, the patients treated with PEN combined with PCD and irrigation had a lower incidence of postoperative delayed severe intraabdominal hemorrhage (31.8% vs. 0%; p = 0.04). During the follow-up period, no patients in either group suffered from collection recurrence or external pancreatic fistula requiring surgical intervention. Conclusions: PEN combined with PCD and irrigation was safe and effective for reducing postoperative delayed severe intraabdominal hemorrhage in patients with CR-POPF after PD

    pigp: a pen-based intelligent dynamic lecture system for geometry teaching

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    Computer-based lecture presentation systems have been widely used in classroom. Yet the teachers can not edit the slides in class according to the actual classroom feedback, which goes against active learning. Although Ink annotation can to s
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