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| 1 | Oxaliplatin plus irinotecan vs irinotecan as second-line treatment in pancreatic cancer patients:a randomized–controlled open-label Phase II study显示文摘Background:Limited second-line therapeutic options are available for metastasis pancreatic cancer(mPC).We aimed to explore the efficacy and safety of oxaliplatin plus irinotecan(IROX)in mPC patients.Methods:This is an open-label,Phase 2,randomized study of mPC patients(aged 18–75 years)who failed when using gemcitabine plus S-1 as first-line therapy.Block randomization with a block size of four was used to randomly assign patients(1:1)between October 2015 and December 2017 to receive either IROX(oxaliplatin 85mg/m2 and irinotecan 160mg/m2)or irinotecan monotherapy(irinotecan 180mg/m^(2))until disease progression,unacceptable adverse events,or consent withdrawal.The primary end point was overall survival,and the secondary end points were progression-free survival,overall response rate,and adverse event rate.Results:A total of 74 patients were enrolled in this study,including 44 males and 30 females,with an average age of 61 years.The median overall survival was 10.2 and 6.7 months(adjusted hazard ratio[HR],0.7;95%confidence interval[CI],0.4–1.2;P=0.20)and the median progression-free survival was 5.1 and 2.3 months(adjusted HR,0.4;95%CI,0.2–0.6;P<0.01)in the IROX group and irinotecan group,respectively.The overall response rates were 18.4%(7/38)in the IROX group and 5.5%(2/36)in the irinotecan group(P=0.06).Grade 3–4 adverse events occurred in 34%(13/38)of patients in the IROX group and 19%(7/36)of patients in the irinotecan group(P=0.15).Conclusions:IROX had no significant survival benefit over irinotecan monotherapy in our study.However,IROX reduced the risk of disease progression by 60%,with acceptable toxicity. | Hangyu Zhang Zhou Tong Lulu Liu Qihan Fu Xudong Zhu Xiaomeng Dai Xuanwen Bao Weijia Fang Yi Zheng Peng Zhao | 2023 | Gastroenterology Report2023，11，1： | 0 |
| 2 | Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases显示文摘Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Therefore,we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls(HC)to analyze neutralizing antibodies(NAbs)against SARS-CoV-2 prototype and BA.4/5 variant,anti-receptor binding domain(RBD)IgG,and total anti-SARS-CoV-2 antibodies.Serum levels of the total anti-SARS-CoV-2 antibodies,anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose,but were relatively lower than those of HCs.Induced humoral responses decreased over time after booster vaccination.The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold.All four SARS-CoV-2 antibodies,including total anti-SARS-CoV-2 antibodies,anti-RBD IgG and NAbs against prototype and BA.4/5,were lower in patients with severe CLD than those with non-severe CLD.After booster shot,age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients.Additionally,white blood cell counts and hepatitis B core antibodies were the protective factors,and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies.Overall,our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines.All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak.CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5,which hindered the protective effect of the booster shot against Omicron prevalence.Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients. | Yongmei Liu Jianhua Lu Haoting Zhan Wenfang Yuan Xiaomeng Li Haiyan Kang Haolong Li Yongliang Chen Linlin Cheng Xingli Sun Haojie Zheng Wei Wang Erhei Dai Yongzhe Li | 2023 | Virologica Sinica2023，38，5： | 0 |
| 3 | Identification,characterization,and verification of miR399 target gene in grape显示文摘The microRNA miR399 plays an important role in phosphorus signal transduction pathways in plants.Previously,miR399 was shown to be closely associated with berry ripening in grape(Vitis vinifera).The objective of the present study was to elucidate the evolutionary characteristics of the miR399 gene family in grape and to verify the cleavage effect on the target genes.Grape miR399s were identified by miRNA sequencing and retrieval from the miRBase database.The mature sequences and precursor sequences were subjected to phylogenetic analysis to reconstruct evolutionary trees,as well as secondary structure analysis of the precursor sequence,and prediction of target genes.The cisacting elements in the miR399 promoter were predicted and the cleavage effect of grape miR399b on its target genes was verified.The grape miR399 family comprised nine precursor sequences and nine mature sequences.The precursor sequences formed a typical and stable stem—loop structure.The minimum folding free energy ranged from-55.70 kcal·mol^(-1)to-37.40 kcal·mol^(-1).Multiple sequence alignment revealed that the miR399 family was highly conserved.The grape miR399 family was phylogenetically closely related to peach,apple,and citrus miR399s.Grape miR399s were predicted to target inorganic phosphate transporter 1—3,phospholipase D delta-like,and beta-glucuronosyltransferase.The cleavage effect of grape miR399b on the target genes was verified by means of a dual-luciferase assay and 5’RLM-RACE.Histochemical GUS staining showed that the promoter activity of miR399b was promoted by GA3treatment. | Maosong Pei Hainan Liu Tonglu Wei Huiying Jin Yihe Yu Mengting Ma Xiaomeng Song Rundong Dai Dalong Guo | 2024 | Horticultural Plant Journal2024，10，1： | 0 |
| 4 | The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-κB activation and the innate immune response显示文摘Activation of the TAK1 signalosome is crucial for mediating the innate immune response to pathogen invasion and is regulated by multiple layers of posttranslational modifications,including ubiquitination,SUMOylation,and phosphorylation;however,the underlying molecular mechanism is not fully understood.In this study,TRIM60 negatively regulated the formation and activation of the TAK1 signalosome.Deficiency of TRIM60 in macrophages led to enhanced MAPK and NF-κB activation,accompanied by elevated levels of proinflammatory cytokines but not IFN-I.Immunoprecipitation-mass spectrometry assays identified TAB2 as the target of TRIM60 for SUMOylation rather than ubiquitination,resulting in impaired formation of the TRAF6/TAB2/TAK1 complex and downstream MAPK and NF-κB pathways.The SUMOylation sites of TAB2 mediated by TRIM60 were identified as K329 and K562;substitution of these lysines with arginines abolished the SUMOylation of TAB2.In vivo experiments showed that TRIM60-deficient mice showed an elevated immune response to LPS-induced septic shock and L.monocytogenes infection.Our data reveal that SUMOylation of TAB2 mediated by TRIM60 is a novel mechanism for regulating the innate immune response,potentially paving the way for a new strategy to control antibacterial immune responses. | Zhiwen Gu Xueying Chen Wenyong Yang Yu Qi Hui Yu Xiaomeng Wang Yanqiu Gong Qianqian Chen Bo Zhong Lunzhi Dai Shiqian Qi Zhiqiang Zhang Huiyuan Zhang Hongbo Hu | 2021 | Cellular & Molecular Immunology2021，18，8： | 0 |
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