Objective: To compare Quanti-FERON-TB Gold In-Tube (QFT-GIT) test and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in children. Methods: In this cross-sectional study, 64 participants ...Objective: To compare Quanti-FERON-TB Gold In-Tube (QFT-GIT) test and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in children. Methods: In this cross-sectional study, 64 participants who were between 3 months and 14 years old and had close contact with smear-positive pulmonary tuberculosis were included. Both QFT-GIT test and TST were done and the results were analyzed by SPSS software and Kappa test. Results: The distribution of gender and age according to QFT-GIT and TST results were matched (P>0.05). Overall agreement between QFT-GIT and TST for diagnosis of latent tuberculosis infection in children was 75%. In addition, the contingency coefficient was 0.257, and the Kappa measure of agreement was 0.246 (P=0.034). Conclusions: Compared to TST, QFT-GIT shows no apparent advantage for diagnosis of latent tuberculosis infection in children.展开更多
OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin's lymphoma (DLBCL).METHODS From January 2003 to July ...OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin's lymphoma (DLBCL).METHODS From January 2003 to July 2008, 51 patients received CHOP-like chemotherapy (cyclophosphamide 750 mg/m2, epirubicin 80 mg/m2, vindesine 2.8 mg/m2 on day 1, and prednisolone 100 mg/day on day 1 to day 5). Thirty-one patients received CHOPR-like treatment (rituximab 375 mg/m2 1 day before CHOP-like chemotherapy). Twenty patients received CHOP-like regimen in combination with peginterferon (pegIFN) (1μg/kg on day 5) and rituximab (on day 6).RESULTS -The CR (complete remission) rate in the CHOPR-like (with or without pegIFN) group and in the CHOP-like group was 78.4% and 45.1% (P = 0.005), respectively. The estimated mean time of overall survival (OS) in the CHOPR-like group and CHOP- like group was 58.7 ± 2.8 and 36.4 ±3.4 months, respectively (P = 0.002). The rates of CR and OR (overall remission) in CHOPR- like with IFN arm were 85.0% and 95.0%, and the rates of those in CHOPR-like without IFN arm were 74.2% and 87.0% (P 〉 0.05). The estimated mean time of 4-year-PFS (progression- free survival) in CHOPR-like with IFN arm and in CHOPR-like without IFN arm was 62.9 ±3.0 months and 51.0 ± 4.6 months (P = 0.092), respectively. In the CHOPR-like with IFN arm, no patient relapsed after achieving CR, while the estimated rate of 4-year- DFS (disease-free survival) in the patients who reached CR in the CHOPR-like without IFN arm was (63.4 ± 19.3)% (P = 0.061). CONCLUSION Rituximab combined with CHOP-like chemotherapy improved the prognosis of DLBCL patients. The IFN may help to improve the quality and duration of response of DLBCL patients treated with rituximab and CHOP-like regimen.展开更多
Introduction:To identify Novaferon(Nova),a novel recombinant protein of interferon(IFN)-α,antiviral activity against ancestral severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and Omicron variant in vitro.M...Introduction:To identify Novaferon(Nova),a novel recombinant protein of interferon(IFN)-α,antiviral activity against ancestral severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and Omicron variant in vitro.Methods:Vero cells were infected with SARSCoV-2 and Omicron variant in a biosafety level-3 laboratory.And viral replications were accessed using quantitative real-time reverse transcription polymerase chain reaction(RT-PCR).Results:Results demonstrated that Nova has effective inhibition against ancestral SARS-CoV-2 and Omicron variant in vitro.Discussion:The in vivo effects of Nova need to be further tested in animal models.And large-scale randomized double-blind clinical trials are needed to reveal its potentially clinical application.展开更多
Target of rapamycin(TOR)kinase is an evolutionarily conserved major regulator of nutrient metabolism and organismal growth in eukaryotes.In plants,nutrients are remobilized and reallocated between shoots and roots und...Target of rapamycin(TOR)kinase is an evolutionarily conserved major regulator of nutrient metabolism and organismal growth in eukaryotes.In plants,nutrients are remobilized and reallocated between shoots and roots under low-nutrient conditions,and nitrogen and nitrogen-related nutrients(e.g.,amino acids)are key upstream signals leading to TOR activation in shoots under low-nutrient conditions.However,how these forms of nitrogen can be sensed to activate TOR in plants is still poorly understood.Here we report that the Arabidopsis receptor kinase FERON IA(FER)interacts with the TOR pathway to regulate nutrient(nitrogen and amino acid)signaling under low-nutrient conditions and exerts similar metabolic effects in response to nitrogen deficiency.We found that FER and its partner,RPM1-induced protein kinase(RIPK),interact with the TOR/RAPTOR complex to positively modulate TOR signaling activity.During this process,the receptor complex FER/RIPK phosphorylates the TOR complex component RAPTOR1B.The RALF1 peptide,a ligand of the FER/RIPK receptor complex,increases TOR activation in the young leaf by enhancing FER-TOR interactions,leading to promotion of true leaf growth in Arabidopsis under lownutrient conditions.Furthermore,we showed that specific amino acids(e.g.,Gin,Asp,and Gly)promote true leaf growth under nitrogen-deficient conditions via the FER-TOR axis.Collectively,our study reveals a mechanism by which the RALF1-FER pathway activates TOR in the plant adaptive response to low nutrients and suggests that plants prioritize nutritional stress response over RALF1-mediated inhibition of cell growth under low-nutrient conditions.展开更多
The covalent attachment of protein-resistant polymers to therapeutic proteins is a widely used method for extending their in vivo half-lives; however, the effect of molecular weight of polymer on the in vitro and in v...The covalent attachment of protein-resistant polymers to therapeutic proteins is a widely used method for extending their in vivo half-lives; however, the effect of molecular weight of polymer on the in vitro and in vivo functions of protein-polymer conjugates has not been well elucidated. Herein we report the effect of molecular weight of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) on the in vitro and in vivo properties of C-termi- nal interferon-alpha (IFN)-POEGMA conjugates. Increasing the molecular weight of POEGMA decreased the in vitro activity of IFN-ct but increased its thermal stability and in vivo pharmacokinetics. Intriguingly, the in vivo antitumor efficacy of IFN-a was increased by increasing the POEGMA molecular weight from ca. 20 to 60 kDa, but was not further increased by increasing the molecular weight of POEGMA from ca. 60 to 100 kDa due to the neutralization of the improved pharmacokinetics and the reduced in vitro activity. This finding offers a new viewpoint on the molecular size rationale for designing next-generation protein-polymer conjugates, which may benefit patients by reducing admin- istration frequency and adverse reactions, and improving therapeutic efficacy.展开更多
950335 Preliminary study on the treatment of chil-dren HBV associated glomerulonephritis with humanrecombinant α<sub>1</sub> interferon(rhiFNα1).FANG Lijun(方利君),et al.Pediatr Hosp,Shanghai Med Uni...950335 Preliminary study on the treatment of chil-dren HBV associated glomerulonephritis with humanrecombinant α<sub>1</sub> interferon(rhiFNα1).FANG Lijun(方利君),et al.Pediatr Hosp,Shanghai Med Univ,Shang-hai,200032.Chin J Nephrol 1994;10(6):329-331.Three cases of HBV associated glomerulonephritis(HBV-GN) are treated by human recombinant inter-feron (rhIFNα<sub>1</sub>) made in China.All of these cases havemanifestation of nephrotic syndrome.Their clinicalcharacteristics,pathological findings and展开更多
To investigate adenoviral vector mediated exogenous gene expression in mouse lungs and the effect of mIFN γ transgene expression on allergen induced pulmonary eosinophil infiltration in a murine asthmatic model ...To investigate adenoviral vector mediated exogenous gene expression in mouse lungs and the effect of mIFN γ transgene expression on allergen induced pulmonary eosinophil infiltration in a murine asthmatic model Methods LacZ marker gene was transduced into CD 1 mouse airway epithelial cells by installation of a replication deficient adenovirus with LacZ gene (AdCMVLacZ) 5×10 9 plaque forming unit (pfu) in the intratrachea or nostril C57 mice were sensitized intraperitoneally and challenged by aerosol with ovalbumin (OVA) to produce an asthmatic model AdCMVmIFNγ 5×10 9 pfu was administered via nostril in asthmatic mice 48 h before OVA challenge Sera, bronchial alveolar lavage (BAL) and lungs were recovered 48 h after OVA challenge Results After administration with AdCMVLacZ by intratracheal installation or nose drop, the lungs revealed a high level of widespread LacZ transduction with X gal staining, mainly along airways IFN γ via adenoviral vector transduction could be overexpressed both in vitro and in vivo (1624 7±1321 5 pg/ml in BAL 96 h after AdCMVIFNγ infection) In AdCMVIFNγ treated asthmatic models, histological evaluation revealed marked suppression of eosinophil peribronchial and perivascular infiltration; the recoverable percentage of eosinophils in BAL was an average of 9 00%±4 58%, which was a statistically significant decrease versus that of the positive control group (75 13%±6 85%) ( P 【0 001) The total cell number in BAL ((145±55 6)×10 3 cells/ml) in AdCMVmIFNγ treated mice also was tremendously reduced compared to the positive control group ((216 6±71 1)×10 3 cells/ml) Conclusions Adenoviral vector was able to overexpress exogenous gene in murine lungs IFN γ overexpression via adenoviral vector in pulmonary epithelia in vivo can abrogate allergen induced eosinophilic infiltration in lungs in an asthmatic model, which may suggest a new preventively therapeutic method for cytokine immunogenetic transfer in allergic asthma展开更多
文摘Objective: To compare Quanti-FERON-TB Gold In-Tube (QFT-GIT) test and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in children. Methods: In this cross-sectional study, 64 participants who were between 3 months and 14 years old and had close contact with smear-positive pulmonary tuberculosis were included. Both QFT-GIT test and TST were done and the results were analyzed by SPSS software and Kappa test. Results: The distribution of gender and age according to QFT-GIT and TST results were matched (P>0.05). Overall agreement between QFT-GIT and TST for diagnosis of latent tuberculosis infection in children was 75%. In addition, the contingency coefficient was 0.257, and the Kappa measure of agreement was 0.246 (P=0.034). Conclusions: Compared to TST, QFT-GIT shows no apparent advantage for diagnosis of latent tuberculosis infection in children.
文摘OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin's lymphoma (DLBCL).METHODS From January 2003 to July 2008, 51 patients received CHOP-like chemotherapy (cyclophosphamide 750 mg/m2, epirubicin 80 mg/m2, vindesine 2.8 mg/m2 on day 1, and prednisolone 100 mg/day on day 1 to day 5). Thirty-one patients received CHOPR-like treatment (rituximab 375 mg/m2 1 day before CHOP-like chemotherapy). Twenty patients received CHOP-like regimen in combination with peginterferon (pegIFN) (1μg/kg on day 5) and rituximab (on day 6).RESULTS -The CR (complete remission) rate in the CHOPR-like (with or without pegIFN) group and in the CHOP-like group was 78.4% and 45.1% (P = 0.005), respectively. The estimated mean time of overall survival (OS) in the CHOPR-like group and CHOP- like group was 58.7 ± 2.8 and 36.4 ±3.4 months, respectively (P = 0.002). The rates of CR and OR (overall remission) in CHOPR- like with IFN arm were 85.0% and 95.0%, and the rates of those in CHOPR-like without IFN arm were 74.2% and 87.0% (P 〉 0.05). The estimated mean time of 4-year-PFS (progression- free survival) in CHOPR-like with IFN arm and in CHOPR-like without IFN arm was 62.9 ±3.0 months and 51.0 ± 4.6 months (P = 0.092), respectively. In the CHOPR-like with IFN arm, no patient relapsed after achieving CR, while the estimated rate of 4-year- DFS (disease-free survival) in the patients who reached CR in the CHOPR-like without IFN arm was (63.4 ± 19.3)% (P = 0.061). CONCLUSION Rituximab combined with CHOP-like chemotherapy improved the prognosis of DLBCL patients. The IFN may help to improve the quality and duration of response of DLBCL patients treated with rituximab and CHOP-like regimen.
基金National Key R&D Program of China(2021YFC0863300).
文摘Introduction:To identify Novaferon(Nova),a novel recombinant protein of interferon(IFN)-α,antiviral activity against ancestral severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and Omicron variant in vitro.Methods:Vero cells were infected with SARSCoV-2 and Omicron variant in a biosafety level-3 laboratory.And viral replications were accessed using quantitative real-time reverse transcription polymerase chain reaction(RT-PCR).Results:Results demonstrated that Nova has effective inhibition against ancestral SARS-CoV-2 and Omicron variant in vitro.Discussion:The in vivo effects of Nova need to be further tested in animal models.And large-scale randomized double-blind clinical trials are needed to reveal its potentially clinical application.
基金supported by grants from the National Natural Science Foundation of China(NSFC-31900232,31871396,and 31571444)+3 种基金the Natural Science Foundation of Hunan Province(2020JJ5049)the Science and Technology Innovation Program of Hunan Province(2020WK2014,and 2022WK2007)the Key Scientific and Technological Project of Henan Province(212102110446)the China Postdoctoral Science Foundation(2018M642972).
文摘Target of rapamycin(TOR)kinase is an evolutionarily conserved major regulator of nutrient metabolism and organismal growth in eukaryotes.In plants,nutrients are remobilized and reallocated between shoots and roots under low-nutrient conditions,and nitrogen and nitrogen-related nutrients(e.g.,amino acids)are key upstream signals leading to TOR activation in shoots under low-nutrient conditions.However,how these forms of nitrogen can be sensed to activate TOR in plants is still poorly understood.Here we report that the Arabidopsis receptor kinase FERON IA(FER)interacts with the TOR pathway to regulate nutrient(nitrogen and amino acid)signaling under low-nutrient conditions and exerts similar metabolic effects in response to nitrogen deficiency.We found that FER and its partner,RPM1-induced protein kinase(RIPK),interact with the TOR/RAPTOR complex to positively modulate TOR signaling activity.During this process,the receptor complex FER/RIPK phosphorylates the TOR complex component RAPTOR1B.The RALF1 peptide,a ligand of the FER/RIPK receptor complex,increases TOR activation in the young leaf by enhancing FER-TOR interactions,leading to promotion of true leaf growth in Arabidopsis under lownutrient conditions.Furthermore,we showed that specific amino acids(e.g.,Gin,Asp,and Gly)promote true leaf growth under nitrogen-deficient conditions via the FER-TOR axis.Collectively,our study reveals a mechanism by which the RALF1-FER pathway activates TOR in the plant adaptive response to low nutrients and suggests that plants prioritize nutritional stress response over RALF1-mediated inhibition of cell growth under low-nutrient conditions.
基金financially supported by Grants from the National Natural Science Foundation of China (21274043 and 21534006).
文摘The covalent attachment of protein-resistant polymers to therapeutic proteins is a widely used method for extending their in vivo half-lives; however, the effect of molecular weight of polymer on the in vitro and in vivo functions of protein-polymer conjugates has not been well elucidated. Herein we report the effect of molecular weight of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) on the in vitro and in vivo properties of C-termi- nal interferon-alpha (IFN)-POEGMA conjugates. Increasing the molecular weight of POEGMA decreased the in vitro activity of IFN-ct but increased its thermal stability and in vivo pharmacokinetics. Intriguingly, the in vivo antitumor efficacy of IFN-a was increased by increasing the POEGMA molecular weight from ca. 20 to 60 kDa, but was not further increased by increasing the molecular weight of POEGMA from ca. 60 to 100 kDa due to the neutralization of the improved pharmacokinetics and the reduced in vitro activity. This finding offers a new viewpoint on the molecular size rationale for designing next-generation protein-polymer conjugates, which may benefit patients by reducing admin- istration frequency and adverse reactions, and improving therapeutic efficacy.
文摘950335 Preliminary study on the treatment of chil-dren HBV associated glomerulonephritis with humanrecombinant α<sub>1</sub> interferon(rhiFNα1).FANG Lijun(方利君),et al.Pediatr Hosp,Shanghai Med Univ,Shang-hai,200032.Chin J Nephrol 1994;10(6):329-331.Three cases of HBV associated glomerulonephritis(HBV-GN) are treated by human recombinant inter-feron (rhIFNα<sub>1</sub>) made in China.All of these cases havemanifestation of nephrotic syndrome.Their clinicalcharacteristics,pathological findings and
基金ThisprojectwassupportedbytheNationalNaturalSciencesFoundationofChina (No 3980 0 0 67)
文摘To investigate adenoviral vector mediated exogenous gene expression in mouse lungs and the effect of mIFN γ transgene expression on allergen induced pulmonary eosinophil infiltration in a murine asthmatic model Methods LacZ marker gene was transduced into CD 1 mouse airway epithelial cells by installation of a replication deficient adenovirus with LacZ gene (AdCMVLacZ) 5×10 9 plaque forming unit (pfu) in the intratrachea or nostril C57 mice were sensitized intraperitoneally and challenged by aerosol with ovalbumin (OVA) to produce an asthmatic model AdCMVmIFNγ 5×10 9 pfu was administered via nostril in asthmatic mice 48 h before OVA challenge Sera, bronchial alveolar lavage (BAL) and lungs were recovered 48 h after OVA challenge Results After administration with AdCMVLacZ by intratracheal installation or nose drop, the lungs revealed a high level of widespread LacZ transduction with X gal staining, mainly along airways IFN γ via adenoviral vector transduction could be overexpressed both in vitro and in vivo (1624 7±1321 5 pg/ml in BAL 96 h after AdCMVIFNγ infection) In AdCMVIFNγ treated asthmatic models, histological evaluation revealed marked suppression of eosinophil peribronchial and perivascular infiltration; the recoverable percentage of eosinophils in BAL was an average of 9 00%±4 58%, which was a statistically significant decrease versus that of the positive control group (75 13%±6 85%) ( P 【0 001) The total cell number in BAL ((145±55 6)×10 3 cells/ml) in AdCMVmIFNγ treated mice also was tremendously reduced compared to the positive control group ((216 6±71 1)×10 3 cells/ml) Conclusions Adenoviral vector was able to overexpress exogenous gene in murine lungs IFN γ overexpression via adenoviral vector in pulmonary epithelia in vivo can abrogate allergen induced eosinophilic infiltration in lungs in an asthmatic model, which may suggest a new preventively therapeutic method for cytokine immunogenetic transfer in allergic asthma