Significant risk and associated factors of active tuberculosis infection in Korean patients with inflammatory bowel disease using anti-TNF agents

AIM:To evaluate the incidence and risk factors of Korean tuberculosis(TB) infection in patients with inflammatory bowel disease(IBD) undergoing anti-TNF treatment.METHODS:The data of IBD patients treated with anti-TNFs in 13 tertiary referral hospitals located in the southeastern region of Korea were collected retrospectively.They failed to show response or were intolerant to conventional treatments,including steroids or immunomodulators.Screening measures for latent TB infection(LTBI)and the incidence and risk factors ofactive TB infection after treatment with anti-TNFs were identified.RESULTS:Overall,376 IBD patients treated with antiTNF agents were recruited(male 255,mean age of anti-TNF therapy 32.5±13.0 years);277 had Crohn’s disease,99 had ulcerative colitis,294 used infliximab,and 82 used adalimumab.Before anti-TNF treatment,screening tests for LTBI including an interferon gamma release assay or a tuberculin skin test were performed in 82.2%of patients.Thirty patients(8%)had LTBI.Sixteen cases of active TB infection including one TB-related mortality occurred during 801 personyears(PY)follow-up(1997.4 cases per 100000 PY)after anti-TNF treatment.LTBI(OR=5.76,95%CI:1.57-21.20,P=0.008)and WBC count<5000 mm3(OR=4.5,95%CI:1.51-13.44,P=0.007)during follow-up were identified as independently associated risk factors.CONCLUSION:Anti-TNFs significantly increase the risk of TB infection in Korean patients with IBD.The considerable burden of TB and marked immunosuppression might be attributed to this risk.

Anti-tubercular peptides:A quest of future therapeutic weapon to combat tuberculosis

Tuberculosis(TB) is a symbolic menace to mankind,infecting almost one third of the world's populace and causing over a million mortalities annually.Mycobacterium tuberculosis(M.tuberculosis) is the key pathogen of TB that invades and replicates inside the host's macrophage.With the emerging dilemma of multi-drug resistant tuberculosis(MDR-TB) and extensivelydrug resistant tuberculosis(XDR-TB),the exigency for developing new TB drugs is an obligation now for worldwide researchers.Among the propitious antimycobacterial agents examined in last few decades,anti-tubercular peptides have been substantiated to be persuasive with multiple advantages such as low immunogenicity,selective affinity to bacterial negatively charged cell envelopes and most importantly divergent mechanisms of action.In this review,we epitomized the current advances in the anti-tubercular peptides,focusing the sources and highlighting the mycobactericidal mechanisms of promising peptides.The review investigates the current anti-tubercular peptides exploited not only from human immune cells,human non-immune cells,bacteria and fungi but also from venoms,cyanobacteria,bacteriophages and several other unplumbed sources.The anti-tubercular peptides of those origins are also known to have unique second non-membrane targets within M.tuberculosis.The present context also describes the several cases that manifested the severe side effects of extant antiTB drugs.The downfall,failure to reach clinical trial phases,inept to MDR- or XDR-TB and severe complications of the currently available anti-tubercular drugs accentuate the imperative necessity to develop efficacious drugs from adequate anti-tubercular peptides.Keeping in view of the emerging trends of drug resistant M.tuberculosis globally and unexampled mycobactericidal characteristics of peptides,the anti-tubercular peptides of varied origins can be used as a potential weapon to eradicatc TB in future by developing new therapeutic drugs.

Pancreatic tuberculosis mimicking pancreatic carcinoma during anti-tuberculosis therapy:A case report

Pancreatic tuberculosis(TB) is a rare condition,even in immunocompetent hosts.A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient.The patient was admitted to our hospital after suffering for nine days from epigastralgia and obstructive jaundice.Computed tomography revealed a pancreatic mass that mimicked a pancreatic head carcinoma.The patient had undergone an operation four months prior for thoracic TB and was undergoing anti-TB therapy.A previous abdominal ultrasound was unremarkable with the exception of gallbladder steroid deposits.The patient underwent surgery due to the progressive discomfort of the upper abdomen and a mass that resembled a pancreatic malignancy.A biopsy of the pancreas and lymph nodes was performed,revealing TB infection.The patient received a cholecystostomy tube and recovered after being administered standard anti-TB therapy for 15 mo.This case is reported to emphasize the rarecontribution of pancreatic TB to pancreatic masses and obstructive jaundice.

Pyrrolidine dithiocarbamate alleviates the anti-tuberculosis drug-induced liver injury through JAK2/STAT3 signaling pathway:An experimental study

Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.

Baseline HBV Load Increases the Risk of Anti-tuberculous Drug-induced Hepatitis Flares in Patients with Tuberculosis

Hepatitis associated anti-tuberculous treatment（HATT） has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus（HBV）. Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Increases in serum transaminase levels of 〉3, 5, and 10 times the upper limit of normal（ULN） were used to define liver damage as mild, moderate, and severe, respectively. Patients with elevated total bilirubin（TBil） levels that were more than 10 times the ULN（〉171 μmol/L） with or without decreased（〈40%） prothrombin activity（PTA） were diagnosed with liver failure. A cohort of 87 patients was analyzed. The incidence of liver damage and liver failure was 59.8%（n=52） and 25.3%（n=22）, respectively. The following variables were correlated with the severity of hepatotoxicity： albumin（ALB） levels, PTA, platelet counts（PLT）, and the use of antiretroviral therapies（P〈0.05）. Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure, and high viral loads were a significant risk factor with an odds ratio（OR） of 2.066. Judicious follow-up of clinical conditions, liver function tests, and coagulation function, especially in patients with high HBV loads and hypoalbuminemia is recommended. It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.

First Line Anti-Tuberculosis Drugs Resistance Patterns of <i>Mycobacterium tuberculosis</i>Isolates from Newly Diagnosed Cases of Tuberculosis

Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.

Evaluation of <i>In-Vitro</i>Anti-Tuberculosis Activity of <i>Tetrapleura tetraptera</i>Crude and Fractions on Multidrug Resistant <i>Mycobacterium tuberculosis</i>

The management, control and elimination of tuberculosis (TB) have been difficult with the advent of HIV and cases of multidrug resistant (MDR-TB) tuberculosis. The cases of multidrug resistance to rifampicin and isoniazid pose greater challenges on first line and second line drugs to eliminate TB. The study is aimed at establishing anti-tuberculosis activity of Tetrapleura tetraptera against Mycobacterium tuberculosis and MDR-TB and the phytochemical present. The leaves of Tetrapleura tetraptera were collected, weighed, dried and pulverized to powder. The pulverized leaves of Tetrapleura tetraptera were subjected to 70% methanol extraction and screened for phytochemical. The crude extract was further purified into fractions using silica gel and thin layer chromatography techniques. M. tuberculosis and MDR-TB were obtained from positive acid fast bacilli sputa of TB patients and confirmed using GeneXpert to differentiate genotypic drug susceptible M. tuberculosis and MDR-TB. The sputa were digested using sodium hydroxide-cysteine technique and cultured in Middlebrook 7H9. The crude extract and fractions were screened for anti-tuberculosis activity using tetrazolium microtitre plate assay. The results showed that Tetrapleura tetraptera crude had activities against M. tuberculosis at 7.4 ± 0 mg/ml and 27.5 ± 0 mg/ml for MDR-TB. One of the fractions inhibited the growth of M. tuberculosis at 0.24 ± 0 mg/ml and MDR-TB at 0.89 ± 0 mg/ml. The phytochemical screened includes tannins, alkaloids, saponins, flavonoids, phenols and resins. T. tetraptra possesses anti-tuberculosis potential at low concentration on MDR-TB and can be a lead compound in drug development for the treatment of tuberculosis and multidrug resistant tuberculosis.

Adverse Drug Reactions in Patients on Second Line Anti-Tubercular Drugs for Drug Resistant Tuberculosis in Rural Tertiary Care Hospital in North India

Introduction: The adverse drug events (ADEs) to second-line anti-TB drugs are one of the major reasons for the patients default on treatment. A general awareness of various adverse drug events (ADE) and their management is essential for the effective management of tuberculosis. Identification of adverse drug reaction profile of patients can be useful for the early detection, management and prevention of adverse drug events. Material and methods: It was a prospective observational study conducted after approved Institutional Ethics Committee. A total of 104 drug resistant tuberculosis patients registered from 1st November 2012 to 31st October 2013 started with second line anti-tubercular drugs under PMDT-RNCP after taking written informed consent. Adverse drug reaction during treatment recorded and assessed by Hart wig and WHO scale. Results: 87% patients experienced adverse drug reactions. Total 346 ADR were reported. Most common were gastritis (65%) and arthralgia (60.6%), others were nausea (35.6%), vomiting (32.7%), hyperuricemia (30.8%), giddiness (27%), anorexia (17.3), generalized weakness (15.4), insomnia (10.6%), psychosis (8.6%), hearing impairment (6.7%), hypersensitivity reaction (5.8%), peripheral neuropathy (4.8%), visual disturbance (3.8%), nephrotoxicity (2.9%), forgetfulness (2.9%), gynaecomastia (1.9%), hypothyroidism (1%), seizure (1%), and thrombocytopenia (1%). Conclusion: Majority of patients experienced wide range adverse drug reactions. Most of patients faced the problem within 2 - 3 months of initiation of treatment and managed by symptomatic. Early identification, prompt management and standardized reporting adverse drug reactions at all the level of healthcare are needed.

SARS-COV-2 Infection and Anti-Tuberculosis Immunity: Temporal Association or Real Protective Role?

Introduction: According to the literature consulted to date, there is epidemiological heterogeneity of Covid-19 between countries depending on their vaccination policy, in particular BCG vaccination. These findings have led to several hypotheses, including the protective role of immunity induced by the BCG tuberculosis vaccine against Covid-19 infection. The immunity induced by the BCG vaccine significantly increases the secretion of pro-inflammatory cytokines, in particular IL-1B, which has been shown to play an essential role in antiviral immunity. This cross-immunity, although not specific, if highlighted, is a real providence that must be taken advantage of in the face of this pandemic. The main objective of this study is to rule out or confirm that anti-tuberculosis immunity protects against SARS-COV-2 in our context. Material and Methods: Two groups will be compared: cases infected with the virus and controls who have never been infected with the virus. Both case and control groups will undergo a tuberculin skin test: the intra dermal tuberculin reaction (IDR). Results: We found that our control group had a high IDR immunity value, with an IDR tuberculin positive percentage of 67.2%. This suggests that immunity to IDR is a protective factor against coronavirus disease. Conclusion: The hypothesis of nonspecific anti-tuberculosis protection deserves further verification studies;it would have large positive repercussions for developing countries.

Use of Cost Effective Semi-Automated (Mannual/Micro) MGIT System over BACTEC 960 to Perform First Line Anti-Tuberculosis Drugs Sensitivity Testing

Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.

Synergistic Effects of 18β-glycyrrhetinic Acid Combined with Antituberculosis Drugs against Mycobacterium tuberculosis

The in vitro antibacterial activities of 18β-glycyrrhetinic acid alone or combined with first-line antituberculosis drugs including isoniazid（INH）,rifampicin（RFP） and streptomycin（SM） against Mycobacterium tuberculosis were detected using MABA method.The minimum inhibitory concentrations（MICs） of18β-glycyrrhetinic acid against M.tuberculosis H37Rv（ATCC 27294） and M.bovis（ATCC 19210） were 50 and 100 μg/m L,respectively.The MICs of two clinical drug-susceptible isolates and six drug-resistant isolates were 25-50 and 100-200 μg/m L,respectively.As 18β-glycyrrhetinic acid combined with INH,RFP and SM,they exhibited synergistic effects against six drug-resistant isolates,and MICs decreased significantly：MIC of INH decreased by 2-32 folds（FICIs 0.125-0.375）;MIC of RFP decreased by 4-8 folds（FICIs 0.240-0.490）;MIC of SM decreased by 4-16 folds（FICIs 0.165-0.460）.Traditional medicine monomer had low cytotoxicity on normal cell BHK-21 and could restraint SMMC fission.The results showed that 18β-glycyrrhetinic acid combined with anti-TB drugs（INH,RFP and SM） had good antibacterial activity against M.tuberculosis.These findings indicated that 18β-glycyrrhetinic acid might serve as the potential therapeutic compound for future development of anti-TB drugs.

Association of TNF-α-238G/A and 308 G/A Gene Polymorphisms with Pulmonary Tuberculosis among Patients with Coal Worker’s Pneumoconiosis

Objectives Tumor necrosis factor-α （TNF-α） may play an important role in host＇s immune response to mycobacterium tuberculosis （M. tuberculosis） infection. This study was to investigate the association of TNF-α gene polymorphism with pulmonary tuberculosis （TB） among patients with coal worker＇s pneumoconiosis （CWP）. Methods A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-α gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism （PCR-RFLP）. Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher＇s exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplieative model with combined OR. All data were analyzed using SAS version 8.2 software. Results No significant difference in frequency of the TNF-α-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls （2,2=5.44, P=-0.07）. But difference in frequency of the TNF-α-308 A allele was identified between them （2,2-5.14, P=0.02）. No significant difference in frequencies of the TNF-α-238 genotype and allele （P=0.23 and P=0.09, respectively） was found between cases and controls either, with combined （GG and AA） OR of 3.96 （95% confidence interval of 1.30-12.09） at the -308 locus of the TNF-α gene, as compared to combination of the TNF-α-238 GG and TNF-α-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-α-238 GG and TNF-α-308 GA genotypes was 1.98 （95% CI of 1.06-3.71） for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-a-308 GG genotype and body mass index （OR=4.92）, as well as an interaction between the TNF-α-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-α-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated. Conclusions TNF-α-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-α-238 A allele was otherwise.

Drug Resistance Pattern in Pulmonary Tuberculosis Patients and Risk Factors Associated with Multi-Drug Resistant Tuberculosis

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.

Clinical Response to Treatment of Central Nervous System Tuberculosis in Non-Human Immunodeficiency Virus-Infected Adolescents and Adults

Introduction: More than half of patients with central nervous system tuberculosis (CNS TB) die or are left with severe neurological deficits despite receiving anti-TB treatment. Aims of the study: This study examined risk factors associated with poor response to initial treatment with four anti-TB drug regimens or three drug regimens with steroids as adjuvant therapy. Methods: This study analyzed medical records from two tertiary hospitals in Busan, Korea, between January 2009 and March 2012. The subjects were non-human immunodeficiency virus (HIV)-infected patients aged ≥16 years with clinical CNS TB. The subjects were divided into two groups according to response to treatment. Results: In totally, 52 patients with CNS TB were included. Of these, 14 (26%) and 38 (73%) showed poor and good responses, respectively. Of the patients with poor response, nine had stage III disease (64.3%) according to the British Medical Research Council (BMRC) staging system. A significantly higher proportion was seen in the good response group (p < 0.05). Patients with positive cerebrospinal fluid (CSF) acid-fast bacillus (AFB) culture, positive sputum AFB culture, positive CSF TB polymerase chain reaction (PCR) results, and brain tuberculoma had poorer responses (p < 0.05). Multivariate analysis to determine risk factors associated with poor response to anti-TB therapy revealed that a poor response was associated with stage III clinical signs upon diagnosis (odds ratio [OR] 32.122;95% confidence interval [CI] 2.221 - 464.605), positive sputum AFB culture (OR 13.624;95% CI 1.066 - 174.149), and tuberculoma on brain images (OR 45.714;95% CI 1.893 - 1104.018). Conclusions: The results demonstrate the importance of identifying the severity of CNS TB and promptly administering anti-TB drugs. It is necessary to perform drug susceptibility testing for anti-TB drugs. Further studies are needed to confirm the correlations between risk factors associated with poor response and anti-TB drug resistance and the other risk factors.

Tuberculosis of the Spine (L5, S1) Secondary to Scrofuloderma with Viral Warts in a 15-Year-Old Male

We report this case of a 15-year-old male who presented to the children outpatient clinic (CHOP) of Abia State University Teaching Hospital (ABSUTH), Aba on the 5th of November 2015. He had tuberculosis (TB) of the skin (scrofuloderma) which was not diagnosed and had received treatment other than anti-TB medication. He now presented 9 years after with multiple body discharging sinuses, cicatricial skin lesions, tuberculosis of the spine (L5, S1) with contracture of the Achilles Tendon and genital warts. Subsequent treatment with full anti-TB drugs led to resolution of his illness. A higher index of suspicion is required for early diagnosis of extrapulmonary TB. Prompt and adequate treatment with anti-TB medication ensures cure in such cases. Appropriate control program is also known to improve the outcome and reduce sequelae.

基于3,5-二溴水杨醛席夫碱镍配合物-氧化石墨烯电化学免疫传感器检测Anti-IgG含量的研究

应用物理吸附法将羊抗人IgG抗原直接固定于3,5-二溴水杨醛席夫碱镍配合物-氧化石墨烯修饰的金电极表面,制备电化学免疫传感器。采用循环伏安法和交流阻抗法对传感器进行表征,结果表明该传感器适合检测Anti-IgG浓度。同时探讨了缓冲液pH值、扫描速度、免疫反应温度、抗原与抗体配比对循环伏安峰电流的影响,结果表明在5-100mV/s扫速范围内,峰电流与扫速呈线性。孵育最优条件为25℃,h-IgG与Anti-IgG配比为1∶1。循环伏安法研究还表明Anti-IgG浓度在0.01-260μg/L范围内,线性关系良好,相关系数r^2=0.993,检出限（S/N=3）为0.006μg/L,据此建立了检测Anti-IgG浓度的新方法。

信号分子IRAK1/4在antiβ-2GPI/β2GPI复合物诱导THP-1细胞表达TF中的作用探讨

目的:探讨IRAK1和IRAK4在antiβ-2GPI/β2GPI复合物诱导单核细胞株THP-1表达组织因子(TF)中的作用。方法:利用荧光定量PCR(Real-time PCR)、TF活性试剂盒分别检测THP-1细胞表达TF mRNA及TF活性;Western blot检测anti-β2GPI/β2GPI复合物诱导THP-1细胞表达IRAK1、磷酸化-IRAK1(p-IRAK1)、IRAK4情况;观察IRAK1/4抑制物是否干预anti-β2GPI/β2GPI复合物诱导THP-1表达TF。结果:Antiβ-2GPI/β2GPI复合物(100μg/ml)诱导THP-1细胞表达TF显著增加(P<0.05 vs control);Antiβ-2GPI/β2GPI复合物(100μg/ml)刺激THP-1细胞表达IRAK1、p-IRAK1、IRAK4(蛋白)显著升高(P<0.05 vscontrol);IRAK1/4抑制物(50μmol/L)能够阻断antiβ-2GPI/β2GPI复合物(100μg/ml)诱导THP-1表达TF及IRAK1磷酸化的效应。结论:antiβ-2GPI/β2GPI复合物诱导THP-1细胞表达TF过程中,信号分子IRAK1/4被激活进而发挥重要作用。

三维Anti de Sitter空间中Lorentzian曲面的S_t^1×S_s^1-值光锥Gauss映射的奇点分类

利用Arnol'd的Legendrian理论,对三维Anti de Sitter空间中Lorentzian曲面进行了研究.引入光维高度函数概念研究了三维Anti de Sitter空间Lorentzian曲面的S1t×S1s-值、光锥Gauss映射的奇点,进行了奇点分类,揭示了类光Causs-kronecker曲率之间的关系;并研究了Lorentzian曲面的一些基本几何性质.

Prevalence and Risk Factors Associated with Adverse Drug Reactions among Previously Treated Tuberculosis Patients in China

We assessed the incidence of adverse drug reactions （ADRs） with anti-TB medications and evaluated the risk factors for developing ADRs in previously treated tuberculosis patients in China. All patients received the first-line anti-TB regimen （2HREZS/6HRE） as recommended by the national guidelines.

Clinical Study on Ganbi Decoction (肝痹汤) in Treating Antituberculotic Agent-Caused Liver Injury

Objective： To study the effect and mechanism of Ganbi decoction （GBD, 肝痹汤 ） in treating patients with antituberculotic agent caused liver injury （ATB-LI）. Methods： One hundred and twenty-eight patients with ATB-LI were randomly assigned to the treated group （ n = 66） and the control group （ n = 62） with the envelop method. Meanwhile, 60 healthy persons were selected as the healthy control group. The treated group was treated by GBD one dose every day with the constituents modified depending on patients＇ symp- toms, and the control group was treated with glucuronolactone tablets and inosine injection. One week was taken as one treatment course. The changes of clinical syndromes, physical signs, T-lymphycyte sub-groups and serum level of nitric oxide （NO） were observed before and after treatment and the recovery time of liver function was recorded. The outcome was compared with that in the healthy control group. Results： In the treated group, 28 patients （42.4%） were cured, 30 （45.5%） improved and 8 （ 12.1% ） ineffectively cured, the total effective rate being 87.9% （58/66）. In the control group, 17 patients （27.4%） were cured, 24 （38.7%） improved, and21 （33.9%）ineffectively cured, the total effective rate being 66.1% （41/62）. The total effective rate in the treated group was significantly higher than that in the control group （ P〈0. 05）. Liver function was improved in both groups, recovery time in the treated group was 12.0±7.0 days, which was significantly shorter than that in the control group （16.0±8.0 days）, showing significant difference between the two groups （ P〈0.05）. The levels of CD3, CD4 and CD8 were significantly higher and level of NO significantly lower in the two groups of patients than those in the healthy control group （ P〈0. 05）, but these parameters were improved more significantly in the treated group after treatment, when compared with those before treatment or with those in the control group, all showing significant difference （P〈0.05）. Conclusion： GBD could prevent ATB-LI, and its mechanism could be by way of reducing NO production induced by endotoxin of macrophage and stimulating the proliferation of T-lymphycyte to elevate immunity.