Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country ...Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country with a high burden of tuberculosis. Method: This study included 581 children and adolescents aged 4 - 19 years who were suspected of having tuberculosis, were latently infected with Mycobacterium tuberculosis, and had received at least one dose of BCG vaccine between April 17, 2019, and February 24, 2021. The study evaluated the TST results of 106 patients who had a positive Quantiferon test and were suspected of having tuberculosis. Results: The study included 581 patients aged between 4 and 19 years. Of these, 106 patients tested positive for the Quantiferon test, while 19 were indeterminate and 456 were negative. The Quantiferon test positivity rate was 18.24%. Among the 106 QFT-Plus-positive cases, 23 patients also tested positive for TST. The difference in distribution was found to be statistically significant. Conclusion: The QFT-Plus test is considered an alternative to TST and other microbiological diagnostic methods for early tuberculosis diagnosis, particularly in children and adolescents.展开更多
In this editorial,we comment on an article published in a recent issue of the World Journal of Clinical Cases.There is a pressing need for reliable tools for diagnosing tuberculosis(TB)of the gastrointestinal tract.De...In this editorial,we comment on an article published in a recent issue of the World Journal of Clinical Cases.There is a pressing need for reliable tools for diagnosing tuberculosis(TB)of the gastrointestinal tract.Despite advancements in the diagnosis and treatment,TB remains a global health challenge.Ali et al demon-strated that TB may mimic gastrointestinal conditions,such as gastric outlet obstruction,causing a delay in the diagnosis.Furthermore,the latter complication is frequently observed during infections,including Helicobacter pylori,and rarely is related to TB,as in the presented case.In line with this,we think that laboratory tests based on interferon-gamma release assays can be a helpful tool for diagnosing latent TB paced in the gastrointestinal tract.Innovative strategies and approaches for diagnosing latent/active extra pulmonary TB are crucial for establishing the diagnosis early and enhancing treatment strategies to mitigate the global burden of TB.展开更多
Objective:To evaluate the performance of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution.Methods:A cross-sectional study was conducted in HI...Objective:To evaluate the performance of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution.Methods:A cross-sectional study was conducted in HIV-infected patients aged 5-18 years receiving antiretroviral treatment with CD4 T-lymphocytes>25%or>500 cells/mm3 for at least 6 months.QuantiF ERON-TB Gold,T-SPOT.TB,and tuberculin skin test were performed in each patient.Results:A total of 50 patients were enrolled with median age of 13.7 years,CD4 counts of 753(IQR:587-989)cells/mm3.Among 27 patients with tuberculosis(16)or tuberculosis exposure(11),8(29.6%)were positive to at least one test,2(7.4%)were positive QuantiFERON-TB Gold,3(11.1%)positive T-SPOT.TB,and 7(25.9%)had tuberculin skin test≥5 mm.Among 23 patients without history of tuberculosis or exposure,all had negative interferon gamma release assays,while 2(8.7%)had positive tuberculin skin test.Conclusions:All tests had low sensitivity despite immune reconstitution.展开更多
Termination of translation in eukaryotes requires two polypeptide chain-release factors, eRF1 and eRF3. eRF1 recognizes stop signals, whereas eRF3 is a ribosome-dependent and eRFl-dependent GTPase. Polypeptide release...Termination of translation in eukaryotes requires two polypeptide chain-release factors, eRF1 and eRF3. eRF1 recognizes stop signals, whereas eRF3 is a ribosome-dependent and eRFl-dependent GTPase. Polypeptide release factor eRF3 consists of N-terminal variable region and C-terminal conserved part. C-terminal part of eRF3 is responsible for termination of the translation, In the present study, the C-terminal of Euplotes octocarinatus eRF3 (eRF3C) and truncate eRF3C lacking 76 amino acids in C-terminal (eRF3Ct) were expressed in Escherichia coll. The recombinant GST-eRF3C and GST-eRF3Ct polypeptides were purifled by affinity chromatography using glutathione Sepharose 4B column. After enzymatic cleavage of GST tail, the eRF3C and eRF3Ct protein were obtained. Pull-down analysis showed that the recombinant GST-eRF3C and GST-eRF3Ct polypeptides interacted with E. octocarinatus polypeptide chain release factor eRF1a. This result suggested that the C-terminal of eRF3 having 76 amino acids were not required for the binding of eRFla in Euplotes octocarinatus.展开更多
Coated microneedles(MNs) are widely used for delivering biopharmaceuticals. In this study, a novel gel encapsulated coated MNs(GEC-MNs) was developed. The water-soluble drug coating was encapsulated with sodium algina...Coated microneedles(MNs) are widely used for delivering biopharmaceuticals. In this study, a novel gel encapsulated coated MNs(GEC-MNs) was developed. The water-soluble drug coating was encapsulated with sodium alginate(SA) in situ complexation gel. The manufacturing process of GEC-MNs was optimized for mass production. Compared to the water-soluble coated MNs(72.02% ± 11.49%), the drug delivery efficiency of the optimized GEC-MNs(88.42% ± 6.72%) was steadily increased, and this improvement was investigated through in vitro drug release. The sustained-release of BSA was observed in vitro permeation through the skin. The rhIFN α-1 b GEC-MNs was confirmed to achieve biosafety and 6-month storage stability. Pharmacokinetics of rhIFN α-1 b in GEC-MNs showed a linearly dosedependent relationship. The AUC of rhIFN α-1 b in GEC-MNs(4.51 ng/ml ·h) was bioequivalent to the intradermal(ID) injection(5.36 ng/ml ·h) and significantly higher than water-soluble coated MNs(3.12 ng/ml ·h). The rhIFN α-1 b elimination half-life of GEC-MNs, soluble coated MNs, and ID injection was 18.16, 1.44, and 2.53 h, respectively. The complexation-based GECMNs have proved to be more efficient, stable, and achieve the sustained-release of watersoluble drug in coating MNs, constituting a high value to biopharmaceutical.展开更多
Gastroduodenal tuberculosis(GD-TB)is exceptionally rare.The clinical manifestations of gastrointestinal TB are diverse and non-specific,which makes diagnosis difficult,leading to delayed diagnosis and high mortality.A...Gastroduodenal tuberculosis(GD-TB)is exceptionally rare.The clinical manifestations of gastrointestinal TB are diverse and non-specific,which makes diagnosis difficult,leading to delayed diagnosis and high mortality.As a peer-reviewer of World Journal of Clinical Cases,I would like to share my opinion on the article published by this journal.The patient had no family history of TB or contact with people with TB.Primary GD-TB presenting as gastric outlet obstruction and normal findings of thoracic computed tomography increased the difficulty of diagnosis and treatment in this patient.The diagnosis and treatment scheme of this typical case have reference value for the clinical treatment of GD-TB.展开更多
In this editorial,we comment on the article by Liu et al.Based on our analysis of a case report,we consider that early screening and recognition of primary nasal tuberculosis are crucial for patients undergoing treatm...In this editorial,we comment on the article by Liu et al.Based on our analysis of a case report,we consider that early screening and recognition of primary nasal tuberculosis are crucial for patients undergoing treatment with tumor necrosis factor inhibitor(TNFi).While TNFi therapy increases the risk of reactivating latent tuberculosis,primary nasal tuberculosis remains rare due to the protective mechanisms of the nasal mucosa.Risk factors for primary nasal tuberculosis include minimally invasive nasal surgery,diabetes,and human immunodefi ciency virus.Patients with early symptoms such as nasal congestion,rhinorrhea,altered olfaction,epistaxis,or ulceration,and unresponsive to conventional antibiotics and antihistamines should undergo early rhinoscopy,possibly followed by repeated tissue biopsies and acid-fast bacilli culture when necessary.When diagnosis is challenging,it is essential to consider local tuberculosis epidemiology and the efficacy of diagnostic antituberculosis treatment.The preferred method for tuberculosis screening is the Interferon Gamma Release Assay,with a general recommendation for screening at 3 and 6 months after initial treatment and then every six months.However,the optimal frequency is not yet consensus-driven and may be increased in economically viable settings.展开更多
结核分支杆菌复合群引起的人和动物结核病,对人类健康及畜牧业发展造成了严重的威胁,早期诊断对于结核病的防控至关重要。在结核病众多诊断方法中,免疫学诊断方法中γ干扰素释放试验具有很好的应用前景。γ干扰素释放试验刺激抗原以结...结核分支杆菌复合群引起的人和动物结核病,对人类健康及畜牧业发展造成了严重的威胁,早期诊断对于结核病的防控至关重要。在结核病众多诊断方法中,免疫学诊断方法中γ干扰素释放试验具有很好的应用前景。γ干扰素释放试验刺激抗原以结核菌素(purified protein derivative,PPD)为主,然而PPD抗原成分复杂,诊断特异性和敏感性有待提高,因此寻找可以代替PPD的特异性刺激抗原成为了研究热点。论文系统综述了近年来报道用于γ干扰素释放试验的刺激抗原,重点概述了刺激抗原的免疫特性、刺激效果以及各类刺激抗原的优势、局限性和应用前景,以期为人和动物结核病的诊断及防控提供参考。展开更多
Background:Interferon-gamma release assay (IGRA) has been used in latent tuberculosis (TB) infection and TB diagnosis,but the results from different high TB-endemic countries are different.The aim of this study w...Background:Interferon-gamma release assay (IGRA) has been used in latent tuberculosis (TB) infection and TB diagnosis,but the results from different high TB-endemic countries are different.The aim of this study was to investigate the value of IGRA in the diagnosis of active pulmonary TB (PTB) in China.Methods:We conducted a large-scale retrospective multicenter investigation to further evaluate the role of IGRA in the diagnosis of active PTB in high TB-epidemic populations and the factors affecting the performance of the assay.All patients who underwent valid T-SPOT.TB assays from December 2012 to November 2015 in six large-scale specialized TB hospitals in China and met the study criteria were retrospectively evaluated.Patients were divided into three groups:Group 1,sputum culture-positive PTB patients,confirmed by positive Mycobacterium tuberculosis sputum culture;Group 2,sputum culture-negative PTB patients;and Group 3,non-TB respiratory diseases.The medical records of all patients were collected.Chi-square tests and Fisher's exact test were used to compare categorical data.Multivariable logistic analyses were performed to evaluate the relationship between the results of T-SPOT in TB patients and other factors.Results:A total of 3082 patients for whom complete information was available were included in the investigation,including 905 sputum culture-positive PTB cases,914 sputum cultmre-negative PTB cases,and 1263 non-TB respiratory disease cases.The positive rate of T-SPOT.TB was 93.3% in the culture-positive PTB group and 86.1% in the culture-negative PTB group.In the non-PTB group,the positive rate of T-SPOT.TB was 43.6%.The positive rate of T-SPOT.TB in the culture-positive PTB group was significantly higher than that in the culture-negative PTB group (x2 =25.118,P 〈 0.01),which in turn was significantly higher than that in the non-TB group (x2 =566.l 16,P 〈 0.01).The overall results were as follows:sensitivity,89.7%;specificity,56.37%;positive predictive value,74.75%;negative predictive value,79.11%;and accuracy,76.02%.Conclusions:High false-positive rates of T-SPOT.TB assays in the non-TB group limit the usefulness as a single test to diagnose active TB in China.We highly recommend that IGRAs not be used for the diagnosis of active TB in high-burden TB settings.展开更多
AIM:Interferon α2b (IFNα2b) and thymosin α1 (Tα1) exhibit synergic effects in the treatment of hepatitis B and hepatitis C when used together. For developing a fusion protein drug, fusion proteins of IFNα2b and T...AIM:Interferon α2b (IFNα2b) and thymosin α1 (Tα1) exhibit synergic effects in the treatment of hepatitis B and hepatitis C when used together. For developing a fusion protein drug, fusion proteins of IFNα2b and Ta1 linked by different lengths of (G4S)n(n = 1-3) were constructed and expressed in Pichia pastoris. METHODS: Using PCR and molecular clone techniques, the fusion genes of IFNα2b-(G4S)n-Tα1 (n = 1-3) were constructed and subcloned into the eukaryotic expression vector pPIC9. After transformation of these plasmids into P. pastoris, the expressed fusion proteins IFNα2b-(G4S) n-Tα1 (n = 1-3) were obtained. These proteins were purified through diethylaminoethyl (DEAE) affinity chromatography and Superdex?75 gel filtration and analyzed by SDS-PAGE and Western blot. Antiviral and E-rosette assays were used to investigate the bioactivities of these fusion proteins. RESULTS: DNA sequencing confirmed that the fusion genes of IFNa2b-(G4S)n-Tα1 (n= 1-3) were correctly cloned to the pPIC9 vector. The recombinant IFNα2b-(G4S)n-Tα1 (n = 1-3) fusion proteins expressed in P. pastoris were purified with DEAE and Superdex?75 gel filtration chromatography. The fusion proteins could be observed on sodium dodecylsulfate-polyacrylamide gel electrophoresis with molecular weight (MW) of 23.2, 22.9, and 22.6 ku, respectively, and reacted to the IFNa2b monoclonal antibody and Tal polyclonal antibody. The purified fusion proteins exhibit antiviral activity and can enhance the percentage of E-rosette-forming-cell in E-rosette assay. CONCLUSION: The recombinant IFNa2b-(G4S)n-Tα1 (n = 1-3) fusion proteins were successfully expressed in P. pastoris. Purified fusion proteins exhibit both antiviral activity of IFNa2b and immunomodulatory activity of Tal in vitro. These results will be the basis for further evaluation of the fusion proteins' function in vivo.展开更多
Background:Quick diagnosis of smear-negative pulmonary tuberculosis(TB)and extra-pulmonary TB are urgently needed in clinical diagnosis.Our research aims to investigate the usefulness of the interferon-γrelease assay...Background:Quick diagnosis of smear-negative pulmonary tuberculosis(TB)and extra-pulmonary TB are urgently needed in clinical diagnosis.Our research aims to investigate the usefulness of the interferon-γrelease assay(IGRA)for the diagnosis of smear-negative pulmonary and extra-pulmonary TB.Methods:We performed TB antibody and TB-IGRA tests on 389 pulmonary TB patients(including 120 smear-positive pulmonary TB patients and 269 smear-negative pulmonary TB patients),113 extra-pulmonary TB patients,81 patients with other pulmonary diseases and 100 healthy controls.Blood samples for the TB-Ab test and the TB-IGRA were collected,processed,and interpreted according to the manufacturer’s protocol.Results:The detection ratio of smear-positive pulmonary TB patients and smear-negative pulmonary TB patients were 90.8%(109 of 120)and 89.6%(241 of 269),respectively.There was no statistically significant difference of its performance between these two sample sets(P>0.05).The detection ratio of positive TB patients and extra-pulmonary TB patients were 90.0%(350 of 389)and 87.6%(99 of 113),respectively,which was not significantly different(P>0.05).Conclusions:In this work,the total detection ratio using TB-IGRA was 89.4%,therefore TB-IGRA has diagnostic values in smear-negative pulmonary TB and extra-pulmonary TB diagnosis.展开更多
Background: Tuberculosis (TB) remains a major global public health challenge. Articular T/3 is an important form of extrapulmonary tuberculosis, and its diagnosis is difficult because of the low sensitivity of trad...Background: Tuberculosis (TB) remains a major global public health challenge. Articular T/3 is an important form of extrapulmonary tuberculosis, and its diagnosis is difficult because of the low sensitivity of traditional methods. The aim of this study was to analyze the diagnostic value of T-SPOT.TB on synovial fluid for the diagnosis of articular TB. Methods: Patients with suspected articular TB were enrolled consecutively between August 2011 and December 2015. T-SPOT.TB was performed on both synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs). The final diagnosis of articular TB was independent of the T-SPOT.TB result. The diagnostic sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB on SFMCs and PBMCs were analyzed. Results: Twenty patients with suspected articular TB were enrolled. Six were diagnosed with articular TB, and 14 patients were diagnosed with other diseases. Sensitivity and specificity were 83% and 86% for T-SPOT.TB on SFMCs, and 67% and 69% for T-SPOT.TB on PBMCs, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of T-SPOT.TB on SFMCs were 71% and 92%, respectively. The PPV and NPV were 50% and 82% for T-SPOT.TB on PBMCs. Conclusion: Sensitivity, specificity, and NPV of T-SPOT.TB on SFMCs appeared higher than that on PBMCs, indicating that T-SPOT. TB on SFMCs might be a rapid and accurate diagnostic test for articular TB.展开更多
Objective: To investigate the antihistamine-releasing effect of a peptide isolated from wasp venom of Vespa orientalis.Methods: This peptide was separated from crude venom by chromatography methods and mass spectromet...Objective: To investigate the antihistamine-releasing effect of a peptide isolated from wasp venom of Vespa orientalis.Methods: This peptide was separated from crude venom by chromatography methods and mass spectrometry. Then various concentrations(2, 4, 8, 16, 32, 64, 128 and256 mmol/L) of the peptide were incubated with mast cells and lactate dehydrogenase assay was performed.Results: No significant effect was observed in lactate dehydrogenase absorbance under128 mmol/L concentration. This implied that the peptide did not cause cell death in mast cells and consequently, histamine release did not happen. Moreover, the results showed the IC50 of mast cells degranulation at 126 mmol/L, which was approximately high implying that this peptide had high selectivity for normal cells and did not cause histamine release from these cells.Conclusions: This would be a great aim in new drug development, in which an agent acts potentially on its target tissue without activating the immune system.展开更多
文摘Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country with a high burden of tuberculosis. Method: This study included 581 children and adolescents aged 4 - 19 years who were suspected of having tuberculosis, were latently infected with Mycobacterium tuberculosis, and had received at least one dose of BCG vaccine between April 17, 2019, and February 24, 2021. The study evaluated the TST results of 106 patients who had a positive Quantiferon test and were suspected of having tuberculosis. Results: The study included 581 patients aged between 4 and 19 years. Of these, 106 patients tested positive for the Quantiferon test, while 19 were indeterminate and 456 were negative. The Quantiferon test positivity rate was 18.24%. Among the 106 QFT-Plus-positive cases, 23 patients also tested positive for TST. The difference in distribution was found to be statistically significant. Conclusion: The QFT-Plus test is considered an alternative to TST and other microbiological diagnostic methods for early tuberculosis diagnosis, particularly in children and adolescents.
基金The European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,Project,No.BG-RRP-2.004-0008.
文摘In this editorial,we comment on an article published in a recent issue of the World Journal of Clinical Cases.There is a pressing need for reliable tools for diagnosing tuberculosis(TB)of the gastrointestinal tract.Despite advancements in the diagnosis and treatment,TB remains a global health challenge.Ali et al demon-strated that TB may mimic gastrointestinal conditions,such as gastric outlet obstruction,causing a delay in the diagnosis.Furthermore,the latter complication is frequently observed during infections,including Helicobacter pylori,and rarely is related to TB,as in the presented case.In line with this,we think that laboratory tests based on interferon-gamma release assays can be a helpful tool for diagnosing latent TB paced in the gastrointestinal tract.Innovative strategies and approaches for diagnosing latent/active extra pulmonary TB are crucial for establishing the diagnosis early and enhancing treatment strategies to mitigate the global burden of TB.
基金supported by the Faculty of Medicine Siriraj Hospital,Mahidol University,Bangkok,Thailand,[Grant Number(IO)R015832028].Oxford Immunotec and Biomed diagnostics(Thailand)provided the T-SPOT.TB test kit
文摘Objective:To evaluate the performance of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution.Methods:A cross-sectional study was conducted in HIV-infected patients aged 5-18 years receiving antiretroviral treatment with CD4 T-lymphocytes>25%or>500 cells/mm3 for at least 6 months.QuantiF ERON-TB Gold,T-SPOT.TB,and tuberculin skin test were performed in each patient.Results:A total of 50 patients were enrolled with median age of 13.7 years,CD4 counts of 753(IQR:587-989)cells/mm3.Among 27 patients with tuberculosis(16)or tuberculosis exposure(11),8(29.6%)were positive to at least one test,2(7.4%)were positive QuantiFERON-TB Gold,3(11.1%)positive T-SPOT.TB,and 7(25.9%)had tuberculin skin test≥5 mm.Among 23 patients without history of tuberculosis or exposure,all had negative interferon gamma release assays,while 2(8.7%)had positive tuberculin skin test.Conclusions:All tests had low sensitivity despite immune reconstitution.
基金This work was supported by grants from National Natural Science Foundation of China(No.30670282,30470239,3030038)Natural Science Foundation of Shanxi Province(No.20041079,20051065).
文摘Termination of translation in eukaryotes requires two polypeptide chain-release factors, eRF1 and eRF3. eRF1 recognizes stop signals, whereas eRF3 is a ribosome-dependent and eRFl-dependent GTPase. Polypeptide release factor eRF3 consists of N-terminal variable region and C-terminal conserved part. C-terminal part of eRF3 is responsible for termination of the translation, In the present study, the C-terminal of Euplotes octocarinatus eRF3 (eRF3C) and truncate eRF3C lacking 76 amino acids in C-terminal (eRF3Ct) were expressed in Escherichia coll. The recombinant GST-eRF3C and GST-eRF3Ct polypeptides were purifled by affinity chromatography using glutathione Sepharose 4B column. After enzymatic cleavage of GST tail, the eRF3C and eRF3Ct protein were obtained. Pull-down analysis showed that the recombinant GST-eRF3C and GST-eRF3Ct polypeptides interacted with E. octocarinatus polypeptide chain release factor eRF1a. This result suggested that the C-terminal of eRF3 having 76 amino acids were not required for the binding of eRFla in Euplotes octocarinatus.
文摘Coated microneedles(MNs) are widely used for delivering biopharmaceuticals. In this study, a novel gel encapsulated coated MNs(GEC-MNs) was developed. The water-soluble drug coating was encapsulated with sodium alginate(SA) in situ complexation gel. The manufacturing process of GEC-MNs was optimized for mass production. Compared to the water-soluble coated MNs(72.02% ± 11.49%), the drug delivery efficiency of the optimized GEC-MNs(88.42% ± 6.72%) was steadily increased, and this improvement was investigated through in vitro drug release. The sustained-release of BSA was observed in vitro permeation through the skin. The rhIFN α-1 b GEC-MNs was confirmed to achieve biosafety and 6-month storage stability. Pharmacokinetics of rhIFN α-1 b in GEC-MNs showed a linearly dosedependent relationship. The AUC of rhIFN α-1 b in GEC-MNs(4.51 ng/ml ·h) was bioequivalent to the intradermal(ID) injection(5.36 ng/ml ·h) and significantly higher than water-soluble coated MNs(3.12 ng/ml ·h). The rhIFN α-1 b elimination half-life of GEC-MNs, soluble coated MNs, and ID injection was 18.16, 1.44, and 2.53 h, respectively. The complexation-based GECMNs have proved to be more efficient, stable, and achieve the sustained-release of watersoluble drug in coating MNs, constituting a high value to biopharmaceutical.
基金Supported by Shenyang Science and Technology Plan Project,No.23-408-3-01The Natural Science Foundation of Liaoning Province,No.2022-MS-435.
文摘Gastroduodenal tuberculosis(GD-TB)is exceptionally rare.The clinical manifestations of gastrointestinal TB are diverse and non-specific,which makes diagnosis difficult,leading to delayed diagnosis and high mortality.As a peer-reviewer of World Journal of Clinical Cases,I would like to share my opinion on the article published by this journal.The patient had no family history of TB or contact with people with TB.Primary GD-TB presenting as gastric outlet obstruction and normal findings of thoracic computed tomography increased the difficulty of diagnosis and treatment in this patient.The diagnosis and treatment scheme of this typical case have reference value for the clinical treatment of GD-TB.
文摘In this editorial,we comment on the article by Liu et al.Based on our analysis of a case report,we consider that early screening and recognition of primary nasal tuberculosis are crucial for patients undergoing treatment with tumor necrosis factor inhibitor(TNFi).While TNFi therapy increases the risk of reactivating latent tuberculosis,primary nasal tuberculosis remains rare due to the protective mechanisms of the nasal mucosa.Risk factors for primary nasal tuberculosis include minimally invasive nasal surgery,diabetes,and human immunodefi ciency virus.Patients with early symptoms such as nasal congestion,rhinorrhea,altered olfaction,epistaxis,or ulceration,and unresponsive to conventional antibiotics and antihistamines should undergo early rhinoscopy,possibly followed by repeated tissue biopsies and acid-fast bacilli culture when necessary.When diagnosis is challenging,it is essential to consider local tuberculosis epidemiology and the efficacy of diagnostic antituberculosis treatment.The preferred method for tuberculosis screening is the Interferon Gamma Release Assay,with a general recommendation for screening at 3 and 6 months after initial treatment and then every six months.However,the optimal frequency is not yet consensus-driven and may be increased in economically viable settings.
文摘结核分支杆菌复合群引起的人和动物结核病,对人类健康及畜牧业发展造成了严重的威胁,早期诊断对于结核病的防控至关重要。在结核病众多诊断方法中,免疫学诊断方法中γ干扰素释放试验具有很好的应用前景。γ干扰素释放试验刺激抗原以结核菌素(purified protein derivative,PPD)为主,然而PPD抗原成分复杂,诊断特异性和敏感性有待提高,因此寻找可以代替PPD的特异性刺激抗原成为了研究热点。论文系统综述了近年来报道用于γ干扰素释放试验的刺激抗原,重点概述了刺激抗原的免疫特性、刺激效果以及各类刺激抗原的优势、局限性和应用前景,以期为人和动物结核病的诊断及防控提供参考。
文摘Background:Interferon-gamma release assay (IGRA) has been used in latent tuberculosis (TB) infection and TB diagnosis,but the results from different high TB-endemic countries are different.The aim of this study was to investigate the value of IGRA in the diagnosis of active pulmonary TB (PTB) in China.Methods:We conducted a large-scale retrospective multicenter investigation to further evaluate the role of IGRA in the diagnosis of active PTB in high TB-epidemic populations and the factors affecting the performance of the assay.All patients who underwent valid T-SPOT.TB assays from December 2012 to November 2015 in six large-scale specialized TB hospitals in China and met the study criteria were retrospectively evaluated.Patients were divided into three groups:Group 1,sputum culture-positive PTB patients,confirmed by positive Mycobacterium tuberculosis sputum culture;Group 2,sputum culture-negative PTB patients;and Group 3,non-TB respiratory diseases.The medical records of all patients were collected.Chi-square tests and Fisher's exact test were used to compare categorical data.Multivariable logistic analyses were performed to evaluate the relationship between the results of T-SPOT in TB patients and other factors.Results:A total of 3082 patients for whom complete information was available were included in the investigation,including 905 sputum culture-positive PTB cases,914 sputum cultmre-negative PTB cases,and 1263 non-TB respiratory disease cases.The positive rate of T-SPOT.TB was 93.3% in the culture-positive PTB group and 86.1% in the culture-negative PTB group.In the non-PTB group,the positive rate of T-SPOT.TB was 43.6%.The positive rate of T-SPOT.TB in the culture-positive PTB group was significantly higher than that in the culture-negative PTB group (x2 =25.118,P 〈 0.01),which in turn was significantly higher than that in the non-TB group (x2 =566.l 16,P 〈 0.01).The overall results were as follows:sensitivity,89.7%;specificity,56.37%;positive predictive value,74.75%;negative predictive value,79.11%;and accuracy,76.02%.Conclusions:High false-positive rates of T-SPOT.TB assays in the non-TB group limit the usefulness as a single test to diagnose active TB in China.We highly recommend that IGRAs not be used for the diagnosis of active TB in high-burden TB settings.
文摘AIM:Interferon α2b (IFNα2b) and thymosin α1 (Tα1) exhibit synergic effects in the treatment of hepatitis B and hepatitis C when used together. For developing a fusion protein drug, fusion proteins of IFNα2b and Ta1 linked by different lengths of (G4S)n(n = 1-3) were constructed and expressed in Pichia pastoris. METHODS: Using PCR and molecular clone techniques, the fusion genes of IFNα2b-(G4S)n-Tα1 (n = 1-3) were constructed and subcloned into the eukaryotic expression vector pPIC9. After transformation of these plasmids into P. pastoris, the expressed fusion proteins IFNα2b-(G4S) n-Tα1 (n = 1-3) were obtained. These proteins were purified through diethylaminoethyl (DEAE) affinity chromatography and Superdex?75 gel filtration and analyzed by SDS-PAGE and Western blot. Antiviral and E-rosette assays were used to investigate the bioactivities of these fusion proteins. RESULTS: DNA sequencing confirmed that the fusion genes of IFNa2b-(G4S)n-Tα1 (n= 1-3) were correctly cloned to the pPIC9 vector. The recombinant IFNα2b-(G4S)n-Tα1 (n = 1-3) fusion proteins expressed in P. pastoris were purified with DEAE and Superdex?75 gel filtration chromatography. The fusion proteins could be observed on sodium dodecylsulfate-polyacrylamide gel electrophoresis with molecular weight (MW) of 23.2, 22.9, and 22.6 ku, respectively, and reacted to the IFNa2b monoclonal antibody and Tal polyclonal antibody. The purified fusion proteins exhibit antiviral activity and can enhance the percentage of E-rosette-forming-cell in E-rosette assay. CONCLUSION: The recombinant IFNa2b-(G4S)n-Tα1 (n = 1-3) fusion proteins were successfully expressed in P. pastoris. Purified fusion proteins exhibit both antiviral activity of IFNa2b and immunomodulatory activity of Tal in vitro. These results will be the basis for further evaluation of the fusion proteins' function in vivo.
基金This work was supported by Grants from the National Natural Sciences Foundation of China(81271893)the Natural Science Foundation of Zhejiang Province(LY12H19002)+2 种基金Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents,the Scientific Research Foundation of the Education Department of Zhejiang Province(Y201534356)the Natural Science Foundation of Zhejiang Medical College(2014B01)Visiting Engineer Program of the Education Department of Zhejiang Province(FG2014011).
文摘Background:Quick diagnosis of smear-negative pulmonary tuberculosis(TB)and extra-pulmonary TB are urgently needed in clinical diagnosis.Our research aims to investigate the usefulness of the interferon-γrelease assay(IGRA)for the diagnosis of smear-negative pulmonary and extra-pulmonary TB.Methods:We performed TB antibody and TB-IGRA tests on 389 pulmonary TB patients(including 120 smear-positive pulmonary TB patients and 269 smear-negative pulmonary TB patients),113 extra-pulmonary TB patients,81 patients with other pulmonary diseases and 100 healthy controls.Blood samples for the TB-Ab test and the TB-IGRA were collected,processed,and interpreted according to the manufacturer’s protocol.Results:The detection ratio of smear-positive pulmonary TB patients and smear-negative pulmonary TB patients were 90.8%(109 of 120)and 89.6%(241 of 269),respectively.There was no statistically significant difference of its performance between these two sample sets(P>0.05).The detection ratio of positive TB patients and extra-pulmonary TB patients were 90.0%(350 of 389)and 87.6%(99 of 113),respectively,which was not significantly different(P>0.05).Conclusions:In this work,the total detection ratio using TB-IGRA was 89.4%,therefore TB-IGRA has diagnostic values in smear-negative pulmonary TB and extra-pulmonary TB diagnosis.
文摘Background: Tuberculosis (TB) remains a major global public health challenge. Articular T/3 is an important form of extrapulmonary tuberculosis, and its diagnosis is difficult because of the low sensitivity of traditional methods. The aim of this study was to analyze the diagnostic value of T-SPOT.TB on synovial fluid for the diagnosis of articular TB. Methods: Patients with suspected articular TB were enrolled consecutively between August 2011 and December 2015. T-SPOT.TB was performed on both synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs). The final diagnosis of articular TB was independent of the T-SPOT.TB result. The diagnostic sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB on SFMCs and PBMCs were analyzed. Results: Twenty patients with suspected articular TB were enrolled. Six were diagnosed with articular TB, and 14 patients were diagnosed with other diseases. Sensitivity and specificity were 83% and 86% for T-SPOT.TB on SFMCs, and 67% and 69% for T-SPOT.TB on PBMCs, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of T-SPOT.TB on SFMCs were 71% and 92%, respectively. The PPV and NPV were 50% and 82% for T-SPOT.TB on PBMCs. Conclusion: Sensitivity, specificity, and NPV of T-SPOT.TB on SFMCs appeared higher than that on PBMCs, indicating that T-SPOT. TB on SFMCs might be a rapid and accurate diagnostic test for articular TB.
基金financially supported by Natural Antimicrobial Centre of Excellence of Shiraz University
文摘Objective: To investigate the antihistamine-releasing effect of a peptide isolated from wasp venom of Vespa orientalis.Methods: This peptide was separated from crude venom by chromatography methods and mass spectrometry. Then various concentrations(2, 4, 8, 16, 32, 64, 128 and256 mmol/L) of the peptide were incubated with mast cells and lactate dehydrogenase assay was performed.Results: No significant effect was observed in lactate dehydrogenase absorbance under128 mmol/L concentration. This implied that the peptide did not cause cell death in mast cells and consequently, histamine release did not happen. Moreover, the results showed the IC50 of mast cells degranulation at 126 mmol/L, which was approximately high implying that this peptide had high selectivity for normal cells and did not cause histamine release from these cells.Conclusions: This would be a great aim in new drug development, in which an agent acts potentially on its target tissue without activating the immune system.