Evaluation of Interferon-Gamma Release Assay Testing and Tuberculin Skin Test for Early Diagnosis of Tuberculosis in Children and Adolescents

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.

Assessing the energy release characteristics during the middle detonation reaction stage of aluminized explosives

Afterburning behind the detonation front of an aluminized explosive releases energy on the millisecond timescale,which prolong the release of detonation energy and the energy release at different stages also shows significant differences.However,at present,there are few effective methods for evaluating the energy release characteristics of the middle reaction stage of such explosives,which can have a duration of tens to hundreds of microseconds.The present work demonstrates an approach to assessing the midstage of an aluminized explosive detonation based on a water push test employing a high degree of confinement.In this method,the explosive is contained in a steel cylinder having one end closed that is installed at the bottom of a transparent water tank.Upon detonation,the gaseous products expand in one direction while forcing water ahead of them.The resulting underwater shock wave and the interface between the gas phase products and the water are tracked using an ultra-high-speed framing and streak camera.The shock wave velocity in water and the expansion work performed by the gaseous detonation products were calculated to assess the energy release characteristics of aluminized explosives such as CL-20 and RDX in the middle stage of the detonation reaction.During the middle stage of the detonation process of these aluminized explosives,the aluminum reaction reduced the attenuation of shock waves and increased the work performed by gas phase products.A higher aluminum content increased the energy output while the presence of oxidants slowed the energy release rate.This work demonstrates an effective means of evaluating the performance of aluminized explosives.

Performance and correlation of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution

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.

Long-release-interval-first real-time scheduling algorithm and its schedulability test

To fulfill the requirements for hybrid real-time system scheduling, a long-release-interval-first （LRIF） real-time scheduling algorithm is proposed. The algorithm adopts both the fixed priority and the dynamic priority to assign priorities for tasks. By assigning higher priorities to the aperiodic soft real-time jobs with longer release intervals, it guarantees the executions for periodic hard real-time tasks and further probabilistically guarantees the executions for aperiodic soft real-time tasks. The schedulability test approach for the LRIF algorithm is presented. The implementation issues of the LRIF algorithm are also discussed. Simulation result shows that LRIF obtains better schedulable performance than the maximum urgency first （MUF） algorithm, the earliest deadline first （EDF） algorithm and EDF for hybrid tasks. LRIF has great capability to schedule both periodic hard real-time and aperiodic soft real-time tasks.

Release test of alliin/alliinase double-layer tablet by HPLC-Allicin determination

A simple, precise and accurate method was developed and validated for the determination of allicin release from alliin/alliinase double-layer tablets. According to Appendix XC Ⅱ of Chinese Pharmacopoeia 2010 edition Volume II, a small glass-method was adopted at the rotational speed of 100 r/min using 100 mL phosphate buffer （pH 6.8） as release medium. The release amount was determined by HPLC with a C18 column （250 mm × 4.6 mm, 5 μm） using the mobile phase consisting of methanol -0.4% carboxylic acid （65：35） at a flow rate of 1 mL/min and UV detection at 242 nm. The current method demonstrates good linearity over the range 4.052- 405.2 μg/mL （r2=0.9999） with an average recovery of 105.5%（RSD= 1.25%）. The accumulative release of alliin/alliinase double-layer tablets had good homogeneity for withinand betweenbatches. The method established is simple, accurate and repeatable for the determination of allicin release from alliin/alliinase double-layer tablets.

Study on the Rapid Method to Predict Longevity of Controlled Release Fertilizer Coated by Water Soluble Resin

The study discussed the rapid method to test and predict the longevity of controlled release fertilizers （CRFs） coated by water soluble resin by using the short-term leaching under higher temperature. Pure water dissolving incubation and higher temperature leaching were used to study the patterns of the nutrient release of the CRFs. The correlation analysis between the days at 25℃ and the hours at 80℃ of Trincote 1 and Trincote 2 for the same cumulative release rates were conducted. Patterns of cumulative nutrient release curve followed one factor quadratic regression equation at each given temperatures, and each of relative coefficient was bigger than 0.995. As the temperature increased, nutrients release of the CRFs increased. The longevity of resin coated CRFs were predicted by use of both the cumulative nutrients release equation at 80℃ and the regression equation of release time needed for the same cumulative release rates between 25 and 80℃. There were only 0.3-6.9% relative errors between the tested longevity and predicted one. In conclusion, the longevity of resin coated CRFs could be predicted more quickly and precisely by use of the higher temperature short-term leaching method than that of the traditional differential release rate. The longevity of resin coated CRF could be rapidly and precisely predicted in a few hours by application of the higher temperature shortterm leaching method.

Enhanced delivery efficiency and sustained release of biopharmaceuticals by complexation-based gel encapsulated coated microneedles:rhIFNα-1b example

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.

Predictive potential of IL-28B genetic testing for interferon based hepatitis C virus therapy in Pakistan: Current scenario and future perspective

In Pakistan which ranked second in terms of hepatitis C virus(HCV) infection, it is highly needed to have an established diagnostic test for antiviral therapy responseprediction. Interleukin 28B(IL-28B) genetic testing is widely used throughout the world for interferon based therapy prediction for HCV patients and is quite helpful not only for health care workers but also for the patients. There is a strong relationship between single nucleotide polymorphisms at or near the IL-28 B gene and the sustained virological response with pegylated interferon plus ribavirin treatment for chronic hepatitis C. Pakistan is a resource limited country, with very low per capita income and there is no proper social security(health insurance) system. The allocated health budget by the government is very low and is used on other health emergencies like polio virus and dengue virus infection. Therefore it is proposed that there should be a well established diagnostic test on the basis of IL-28 B which can predict the antiviral therapy response to strengthen health care set-up of Pakistan. This test once established will help in better management of HCV infected patients.

Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets:Dissolution and release kinetics

A dissolution test for fesoterodine low dose extended-release tablets using liquid chromatographic（LC） method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature（40 1C） using a mobile phase of acetonitrile：methanol：0.03 M ammonium acetate（p H 3.8）（30：15：55, v/v/v）, run at a flow rate of 1.5 m L/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2（paddle） at 100 rpm and 900 m L of phosphate buffer at p H 6.8 as the dissolution medium.Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

Oxidative heat release intensity in coal at low temperatures measured by the hot-wire method

Directly measuring the oxidative heat release intensity at low temperatures is difficult at present.We developed a new method based on heat conduction theory that directly measures heat release intensity of loose coal at low temperatures.Using this method, we calculated the oxidative heat release intensity of differently sized loose coals by comparing the temperature rise of the coal in nitrogen or an air environment.The results show that oxidation heat release intensity of Shenhua coal sized 0～15 mm is 0.001～0.03 W/m3 at 30～90 °C and increases with increasing temperature.The heat release intensity at a given temperature is larger for smaller sized coal.The temperature effect on heat release intensity is muted as the coal size increases.At lower temperature the change in heat release intensity as a function of size becomes smaller.These results show that the test system is usable for practical applications and is easy to operate and is capable of measuring mass samples.

Development of novel-nanobody-based lateral-flow immunochromatographic strip test for rapid detection of recombinant human interferon a2b

Recombinant human interferon a2b(rhIFNa2b)is widely used as an antiviral therapy agent for the treatment of hepatitis B and hepatitis C.The current identification test for rhIFNa2b is complex.In this study,an anti-rhIFNa2b nanobody was discovered and used for the development of a rapid lateral flow strip for the identification of rhIFNa2b.RhIFNa2b was used to immunize an alpaca,which established a phage nanobody library.After five steps of enrichment,the nanobody I22,which specifically bound rhIFNa2b,was isolated and inserted into the prokaryotic expression vector pET28a.After subsequent purification,the physicochemical properties of the nanobody were determined.A semiquantitative detection and rapid identification assay of rhIFNa2b was developed using this novel nanobody.To develop a rapid test,the nanobody I22 was coupled with a colloidal gold to produce lateral-flow test strips.The developed rhIFNa2b detection assay had a limit of detection of 1 mg/mL.The isolation of I22 and successful construction of a lateral-flow immunochromatographic test strip demonstrated the feasibility of performing ligand-binding assays on a lateral-flow test strip using recombinant protein products.The principle of this novel assay is generally applicable for the rapid testing of other commercial products,with a great potential for routine use in detecting counterfeit recombinant protein products.

Energy Release Rate Measurement of Welded Bamboo Joints

Double cantilever beam tests were used to measure the energy release rates of linear vibrational welded moso bamboo joints.The influence of the length of the preserved cracks,the different combinations of the inner and outer bamboo surfaces and the moisture content is studied herein.The experimental compliance method,which is based on linear elastic fracture mechanics and has been shown to be an ideal method,was used to analyze data with the power equation.The results show that the preserved initial crack length does not have a significant effect on the final measured energy release rate,while the moso bamboo combination does affect the properties dramatically.The welded moso bamboo joints with inner-inner surfaces have the highest energy release rate of 122 J/m^2.The average energy release of the outer-outer combination was only 102 J/m^2.The expansion of the cracks also became easier when the moisture content of the welded joints was 18.5%compared to 4.5% and 10.1%.So the moisture resistance of the welded joints should be duly improved.

Mating behavior and sex pheromone release rhythm of Holotrichia parallela(Coleoptera: Melolonthidae)

Mating behavior and sex pheromone release rhythm of Holotrichia parallela was studied in this research. The maximum mating times were 3 for female and 4 for male. Average mating times were 1.06 for female and 0.91 for male. L-isoleucine methyl ester(LIME), a major component of pheromone, increased gradually from 14:00 and peaked at 19:00, then dropped sharply at 20:00 and remained low at 24:00.(R)-(-)-linalool(referred as linalool below) maintained similar levels throughout the study period. Calling and mating activity significantly decreased LIME titer, but not linalool. Analyses of 11 samples collected during calling days(20 d-70 d) revealed that LIME production was affected by female age. LIME titers increased from 20 d to 45 d, and decreased from 45 d to 70 d. While linalool titers remained at similar levels at all sampling dates. The highest ratio between LIME and linalool was 12 and the lowest was 4. Field tests confirmed that the most attractive ratios of LIME: linalool in early season(June 1 to 20) and late season(August 1 to 20) were 6:1, while in the most serious injury stage(June 20 to August 1) was 12:1. This is the first report about circadian rhythmicity of sex pheromone in Holotrichia parallela, which provides a basis for controlling it in field.

Rationale of Timed-Release Analysis and the Improvement of Flotation Experiment

The fundamental aspects of The Timed-Release Analysis (TRA) and some problems are analysed. Having studied the attribute of optimum flotation test results and the way of optimum test conditions, the auther put forward a proposal to improve this test method by adding a new test step of scavenging flotation and using optimum test conditions varied with different fine coals instead of the given ones settled by the TRA norm. Comparison between test results of the two methods of TRA shows that the improved method is very good.

地浸砂岩型铀矿松散岩层单动双管取心钻具的研制与试验

为解决单管钻具取心工艺方法在深部目的层/矿层等松散岩层取心中存在的取心质量差、取心效率低和操作难度大的问题,开展了地浸砂岩型铀矿松散岩层单动双管钻具的研制和试验。通过设计和改进单动机构、断心结构、液力退心机构和快拆机构,研制了两类分别具有可直接液力退心和快速拆卸功能的SD型单动双管钻具。试验结果表明:SD110型双管钻具可在免拆内管的情况下实现地表快速液力退心,提高双管钻具退心效率;SDKC110型钻具可快速拆装更换内管,实现退心和钻进平行作业。与单管钻具相比,SD系列单动双管钻具在松散岩层的平均回次长度提高28.62%,平均机械钻速提高11.61%;与常规单动双管钻具相比,退心操作时间降低了32.69%。SD系列单动双管钻具适用于在松散破碎地层进行取心钻进应用,可有效提高岩心采取效率和岩心质量。

优化T-SPOT.TB在区分脊柱结核与其他脊柱感染中的诊断效能

目的 探讨结核感染T细胞斑点试验(T-SPOT.TB)在脊柱结核(STB)鉴别诊断中的效能,并通过受试者工作特征(ROC)曲线最佳截断值优化诊断效能。方法 收集2010年1月—2019年5月某院脊柱感染患者的临床资料,包括术前T-SPOT.TB检测结果、白细胞计数、C-反应蛋白、血沉、降钙素原和结核抗体等相关数据,根据诊断标准进行临床诊断,分析T-SPOT.TB在术前诊断STB与其他脊柱感染中的灵敏度和特异度,评价优化后的T-SPOT.TB指标的诊断效能。结果 共纳入132例患者,其中78例(59.09%)为STB,54例(40.91%)为非结核脊柱感染。T-SPOT.TB在鉴别诊断STB方面的灵敏度为67.68%,特异度为66.67%。单因素logistic回归分析显示,与非结核脊柱感染比较,T-SPOT.TB检测诊断STB的OR值为4.188(95%CI:1.847~9.974,P<0.001)。优化T-SPOT.TB评价指标,通过绘制ROC曲线,确定ESAT-6、CFP-10、CFP-10+ESAT-6在STB和非结核脊柱感染鉴别诊断中的最佳截断值,分别为12.5、19.5、36,曲线下面积(AUC)分别是0.765 6、0.741 5、0.778 6,均具有较好的诊断性能,其中以CFP-10+ESAT-6的AUC最高。CFP-10+ESAT-6特异性斑点数在脊柱结核诊断中性能更佳,其诊断准确度为75.56%,较优化前T-SPOT.TB的67.42%高。结论 T-SPOT.TB检测在区分STB与非结核脊柱感染方面显示出较高的诊断效能,T-SPOT.TB检测呈阳性,尤其是当CFP-10+ESAT-6的斑点数超过36时,提示脊柱结核的可能性较大。

基于鱼类上溯行为的导鱼堰设计与效果评估

河道内鱼类上溯路径不唯一,聚集位置更是难以预测,对鱼类上溯行为进行有效引导有助于提升过鱼设施进口的效率。为此,该研究提出了一种导鱼堰的概念和设计方法,结合姚家坪水电站的过鱼设施,利用流场三维数值模拟、鱼类洄游(active fish migration,AFM)模型和实鱼试验对导鱼堰的效果进行评估。结果表明:姚家平水利枢纽工程的导鱼堰上下游水面落差为0.36~0.40 m,过堰水流流速可达1.5~2.8 m/s,形成阻鱼的屏障,并在导鱼堰下游侧形成了诱导鱼类向集鱼渠进鱼口游动的唯一低流速上溯通道,鱼类聚集点趋于唯一,验证了导鱼堰方案的合理性。利用鱼类洄游模型对导鱼堰的导鱼效果进行预测,结果表明,下游高水位和低水位2种工况下,90%以上的鱼类游动路径均表现出相似的规律,鱼类沿河道右岸和导鱼堰下游侧的低流速通道上溯,并最终聚集在集鱼渠的进鱼口处。放鱼试验中试验个体全部进入集鱼渠,结果进一步证实导鱼堰可以有效引导鱼类游动路线,并在集鱼渠进鱼口处形成唯一的聚集区。本文提出的导鱼堰丰富了生态水工建筑物的形式,可为过鱼设施进口的水力设计及下游河道的局部整治提供参考。

简化PCOS患者胰岛素释放和糖耐量实验的效果评价

目的研究从检测时间点上简化多囊卵巢综合征(PCOS)患者胰岛素释放和糖耐量实验对评价胰岛素抵抗和糖代谢异常的效果。方法通过回顾性研究,选取2021年8月至2022年8月在我院就诊的320例已完成胰岛素释放和糖耐量试验(临床“金标准”)的PCOS患者,并假设研究对象只接受了简化方法一“空腹血糖和胰岛素检测”或简化方法二“空腹+糖负荷后2 h血糖和胰岛素检测”,评价两种简化方法的敏感度与临床“金标准”的一致性。结果患者总异常(即胰岛素抵抗或糖代谢异常)的发生率为80.0%(256/320),其中,超重/肥胖的患者和体重正常患者的总异常发生率分别为97.5%(115/118)和69.8%(141/202)。对于总异常的检测,超重/肥胖患者中简化方法一和简化方法二的敏感度分别为93.0%和96.5%(后者一致性检验Kappa=0.585);体重正常患者中,两种简化方法的敏感度分别为58.2%和74.5%。对于“糖代谢异常”的检测,超重/肥胖患者中,两种简化方法的敏感度分别为16.7%和100%(后者一致性检验Kappa=1.000)。结论对所有的PCOS患者均应进行胰岛素抵抗和糖代谢异常的检测;对于超重/肥胖PCOS患者,空腹+糖负荷后2 h血糖和胰岛素检测可以代替胰岛素释放和糖耐量实验;对于体重正常的PCOS患者,二种简化方法均有漏诊风险。

端粒酶、γ-干扰素、腺苷酸脱氨酶及结核感染T细胞斑点试验在诊断结核性和恶性胸腔积液中的作用分析

目的 评价端粒酶、γ-干扰素(IFN-γ)、腺苷酸脱氨酶(ADA)及T细胞斑点试验(T-SPOT.TB)检测在诊断结核性和恶性胸腔积液中的价值。方法 纳入40例早期结核性胸膜炎患者(结核组)和40例恶性胸腔积液患者(肿瘤组),分别在治疗前抽取患者胸腔积液及空腹血液,应用酶联免疫吸附分析法检测端粒酶的含量和IFN-γ的浓度,应用比色分析法检测ADA的活性,采用Elispot斑点计数检测T-SPOT.TB阳性率。结果 结核组和肿瘤组的端粒酶含量分别为(1.46±0.73)×10~(-3) nmol/L和(3.34±1.72)×10~(-3) nmol/L,结核组端粒酶含量低于肿瘤组(P<0.01);结核组和肿瘤组的IFN-γ含量分别为(137.44±38.93) U/L和(27.94±8.46) U/L,ADA含量分别为(68.42±9.58) U/L和(15.39±4.43) U/L,2组患者IFN-γ含量和ADA含量比较,差异有统计学意义(P<0.01)。结核组IFN-γ浓度、ADA活性及T-SPOT.TB阳性率均高于肿瘤组(P<0.01)。联合应用端粒酶、IFN-γ、ADA及T-SPOT.TB 4个诊断指标的诊断试验鉴别诊断结核性和恶性胸腔积液的敏感度为0.974,特异度为0.974。结论 联合应用端粒酶、IFN-γ、ADA及T-SPOT.TB 4个诊断指标的诊断试验在结核性胸腔积液和恶性胸腔积液的鉴别诊断中具有重要意义。

γ-干扰素试验在结核病诊断中的临床应用价值

目的分析CLIA检测γ-干扰素试验诊断结核病的临床应用价值。方法选取2023年5月-2023年9月在本院接受检查的疑似结核病患者1616例,以临床最终诊断结果为金标准,判断全自动化学发光法检测γ-干扰素试验在结核病诊断中的诊断效能。结果临床最终诊断结果显示,阳性患者916例,阴性患者700例。γ-干扰素试验结果显示,阳性患者908例,阴性患者708例。CLIA检验γ-干扰素试验在肺外结核中的阳性检出率较高,但与临床最终诊断结果比较差异有统计学意义(P<0.05);在结核病、肺结核、呼吸道疾病、肺部炎症疾病的阳性检出率与临床最终诊断结果比较差异无统计学意义(P>0.05);在结核病中的敏感度、特异度、准确度与临床最终诊断结果比较差异无统计学意义(P>0.05)。结果采用CLIA检测γ-干扰素试验可对结核病进行诊断,可明确患者为结核病或非结核疾病,并且在结核病的诊断中具有较高的敏感度、特异性。