简介：AbstractBackground:Differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) has been a challenge for clinicians in high TB burden countries. The purpose of this study was to improve the accuracy of differential diagnosis of ATB and LTBI by using fluorescent immunospot (FluoroSpot) assay to detect specific Th1 cell immune responses. The novel mycobacterium tuberculosis (MTB) latency-associated antigens Rv1733c and synthetic long peptides derived from Rv1733c (Rv1733c SLP) were used based on virulence factors early secreting antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10).Methods:Fifty-seven ATB cases, including 20 pathogen-confirmed ATB and 37 clinically diagnosed ATB, and 36 LTBI cases, were enrolled between January and December 2017. FluoroSpot assay was used to detect the interferon γ (IFN-γ) and interleukin 2 (IL-2) secreted by the specific T cells after being stimulated with MTB virulence factors ESAT-6 and CFP-10, MTB latency-associated antigens Rv1733c and Rv1733c SLP. The receiver operating characteristic (ROC) curve was used to define the best cutoff value of latency-associated antigens in the use of differentiating ATB and LTBI. The sensitivity, specificity, predictive value, and likelihood ratio of ESAT-6 and CFP-10-FluoroSpot combined with latency-associated antigen in the differential diagnosis of ATB and LTBI were also calculated.Results:Following the stimulation with Rv1733c and Rv1733c SLP, the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP had the largest area under the ROC curve, which was 0.766. With a cutoff value of 1 (spot-forming cells [SFCs]/2.5 × 105 peripheral blood mononuclear cells) for frequency, the sensitivity and specificity of distinguishing ATB from LTBI were 72.2% and 73.7%, respectively. ESAT-6 and CFP-10-FluoroSpot detected the frequency and proportion of single IFN-γ-secreting T cells; the sensitivity and specificity of distinguishing ATB from LTBI were 82.5% and 66.7%, respectively. Combined with the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP on the basis of ESAT-6 and CFP-10-FluoroSpot, the sensitivity and specificity increased to 84.2% and 83.3%, respectively.Conclusion:Rv1733c SLP, combined with ESAT-6 and CFP-10, might be used as a candidate antigen for T cell-based tuberculosis diagnostic tests to differentiate ATB from LTBI.

简介：AbstractTuberculosis (TB) is on the rise in Pakistan and there could be multiple reasons including poverty, difficulty in access to TB treatment services, non-compliance with treatment, social stigma etc. According to the TB program managers, limited treatment and testing sites for tuberculosis and lack of trained human resources play a major role in compromising TB management. A major lacuna in the TB control program is the absence of active contact tracing strategy. This is essential for a disease where positive cases are known to be able to infect a further 10-15 individuals in a year. Tackling tuberculosis in Pakistan has been beleaguered by funding challenges and other systems’ bottlenecks such as lack of skilled human resources and insufficient supply of medicines, despite the fact that disease burden is one of the highest in the world. Although it is a notifiable disease, active case finding, contact tracing and reporting is notoriously low throughout the country. Access to diagnostics and treatment facilities has been limited and stigma attached to the disease remains deeply entrenched among the communities. Researchers have shown that enhanced and active approaches to contact investigation effectively identifies additional patients with TB among household contacts at a relatively modest cost. USAID’s Integrated Health Systems Strengthening and Service Delivery Activity extended support to the Health Departments of Sindh and Khyber Pakhtunkhwa provinces. In collaboration with the two provincial TB programs, community based active contact tracing was conducted on 17,696 individuals, based on the index cases. Among the contacts traced, 243 cases were diagnosed as drug sensitive or drug resistant TB. Awareness sessions were conducted to sensitize people on the various aspects of disease and importance of getting tested. The project also supported establishing three satellite Programmatic Management of Drug Resistant Tuberculosis (PMDT) sites for drug resistant TB treatment, enhancing the programs’diagnostic and testing capacity.

简介：AlthoughithasbeenknownthatγδTcellsmayplayanimportantroleintheimmuneresponsetoinfectionofMycobacteriumtuberculosis(M.tb),themechanismsbywhichtheγδTcellsparticipateintheinnateand/oracquiredimmunitytotuberculosis(TB)havenotbeenfullelucidated.Inthepresentstudy,27patientswithactivepulmonaryTBand16healthydonors(HD)wereperformed.WefoundthatproportionofIL-17-producingcellsamonglymphocytewassimilarbetweenTBpatientsandHD,whereastheproportionsofγδTcellsinIL-17-producingcells(59.2%)andIL-17-producingcellsinγδTcells(19.4%)inperipheralbloodweremarkedlyincreasedinTBpatientswhencomparedtothoseinHD(43.9%and7.7%,respectively).Inaddition,theproportionsofIFN-γ-producingγδTcellsinTBpatientswereobviouslylowerthanthatinHD.Uponre-stimulatedwithM.tbheat-treatedantigen(M.tb-HAg)invitro,fewerIL-17-producingγδTcellsweregeneratedfromHDandTBpatients,whereasIFN-γ-producingγδTcellswereincreasedinTBpatientscomparedtothatinHD.OurfindingsinTBpatientsandhealthyhumanwereconsistentwithothermurineinvestigationthattheIL-17-producingγδTcellsweremainsourceofIL-17inmousemodelofBCGinfection,suggestingthatγδTcellsmightbeinvolvedintheformationoftuberculargranulomainpulmonaryTBpatients,butneedfurtheridentification.

简介：AbstractNearly one-fourth of the world’s population is infected with Mycobacterium tuberculosis (MTB). Female genital tuberculosis (TB) is a common cause of infertility in both developing and undeveloped countries. Furthermore, assisted reproduction treatments and pregnancy potentially increase the risk of TB infection and reactivation. In this study, we present the case of a 28-year-old infertile female without a history of TB who developed an acute miliary TB and pelvic TB after in vitro fertilization-embryo transfer (IVF-ET). Elevated serum estrogen levels during controlled ovarian hyperstimulation and T-lymphocyte function inhibition during pregnancy are the risk factors for MTB infection and reactivation. In her 7th week of gestation, the patient developed fever and spontaneously aborted. Her chest computed tomography images revealed classical miliary TB. Uterine curettage tissue and vaginal secretion samples as well as Gene X-pert MTB/rifampicin (RIF) and TB-RNA test results were positive for MTB. Histological examination of the uterine curettage tissue confirmed the diagnosis of endometrial TB. Treatment with isoniazid, RIF, pyrazinamide, amikacin, and levofloxacin was selected based on the patient’s diagnosis, complications, and test results. Currently, the patient is undergoing anti-TB treatment, and her condition is stable. It is important to rule out the presence of TB in infertile patients before performing IVF-ET to avoid TB dissemination during pregnancy.

简介：AbstractTuberculosis (TB) is among the deadliest infectious diseases worldwide. Although the existing antituberculosis (anti-TB) drugs remain to be effective, the administration of these complex anti-TB drug combinations with obvious toxicity often leads to patients’ nonadherence. This may contribute toward the emergence of drug-resistant strains as well as lead to treatment failure and relapse. Therefore, in the past half century, the main focus of anti-TB drug research was to reduce the frequency of administration and toxicity and improve patients' compliance and drug sensitivity. Following these principles, the development of engineered biosafety materials is one of the most effective and promising methods in resolving these challenges. Compared with traditional drugs, biosafety materials provide a viable platform for treating TB, which are beneficial in reducing the frequency of drug administration and systemic toxicity, improving patients’ compliance and drug sensitivity, and enhancing drug targeting. In this review, we summarized the application of biosafety materials in treatment of TB in recent years and discussed the challenges faced when developing a safe, more effective, and economical pharmacotherapy against TB.

简介：AbstractThe low success rates in the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB), which account for 55% and 34% respectively, led the WHO to conclude that MDR/XDR-TB is a serious public health crisis. However, the virulence of MDR/XDR-Mycobacterium Tuberculosis(Mtb) has not been analyzed in details, which could provide a specific guidance for the control and prevention. In this review, we discuss different aspects of MDR/XDR-Mtb virulence and its relationship to fitness cost by probing the following questions: (1) what mediates the virulence of MDR/XDR-Mtb? (What is the relationship between fitness and virulence of Mtb? (2) Is it possible that drug-resistant Mtb(DR Mtb) can show higher fitness? (3) What is the definite effect on fitness of each drug-resistant mutant? (4) What other important factors affecting fitness in the mutant strain? (5) How to study the virulence of a large number of DR Mtb?And what prevention and control measures will be taken in the future, especially for the high virulent DR Mtb? We therefore summarized the congruent relationship between drug resistance and fitness from the global response-related genes to antibiotic resistance-contributing mutation, provided methods to explore the virulence of DR Mtb. This review may offer some critical information and concise guide to creating strategies for the prevention and control of drug-resistant Mtb.

简介：Theeruptivehistories,stylesofactivityandgeneralmodesofoperationofthemainactiveItalianvolcanoes,Etna,Vulcano,Stromboli,Vesuvio,CampiFlegreiandIschia,aredescribedinashortsummary.

简介：AsoneofthevictoriousAlliesofWorldWarI,ChinaattendedtheParisPeaceConferencein1919.Toacertainextent,theconferencecanberegardedasthetruebeginningofglobalgovernance.ItwasfollowedbytheestablishmentoftheVersailles-WashingtonSystem,thefirstinternationalpatternwithworldparticipation.Althoughitwasinvolvedin

简介：谁料得到宝马出此一招，竟然推出高载客量的前驱轻型客车。对不起，是我说过头了。这款作品现阶段只是概念作，

简介：AbstractIntroduction:Scrofuloderma is caused by Mycobacterium tuberculosis and is the most common form of cutaneous tuberculosis. It remains a significant medical challenge because its clinical manifestations mimic those of various other conditions, making diagnosis difficult. Here, we report a 28-year-old man who had been diagnosed with intestinal tuberculosis but discontinued treatment.Case presentation:He subsequently presented with a 5-month history of multiple non-healing ulcerative lesions on the abdomen with no other significant clinical findings. Ziehl-Neelsen staining of an impression smear taken from the lesions was performed as the preliminary investigation and confirmed the presence of acid-fast bacilli. Histopathologic examination of a skin biopsy specimen, PCR, and the Mantoux test also confirmed the presence of Mycobacterium tuberculosis. The patient began treatment with anti-tubercular drugs and his lesions gradually regressed.Discussion:The most common finding of scrofuloderma is a chronic, painless ulcerative lesion with purulent discharge. Cervical lymph nodes are frequently involved. These clinical features mimic several other bacterial and fungal conditions. However, Ziehl-Neelsen staining of the discharging ulcers can be used as a preliminary test to demonstrate acid fast bacilli in most of the cases. Histopathologic examination of skin biopsy specimen, culture on Lowenstein-Jensen media and PCR can confirm the diagnosis.Conclusion:Although Scrofuloderma is a rare cutaneous manifestation, it is curable with early diagnosis and prompt intervention of antitubercular drugs.

简介：AbstractImportance:Bacteremia tuberculosis (TB) is a severe form of extrapulmonary TB. Studies assessing bacteremia TB in children are limited, especially for HIV-negative children.Objective:To explore the detailed clinical features of the bacteremia TB in children under 18 years of age.Methods:We reviewed the clinical records of the patients retrospectively and collected the strains isolated from their blood cultures. We used mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) to characterize the bacterial genotypes and alamarBlue to determine their drug susceptibility profiles. Polymerase chain reactions and DNA sequencing were used to identify drug-resistant mutations.Results:There were 13 pediatric bacteremia TB patients, 10 of whom were diagnosed with Bacillus Calmette–Guérin (BCG) bacteremia TB. Thirteen patients aged from 0.30 to 11.58 years were enrolled, of whom 76.92% were boys. All had fevers before hospitalization, and 76.92% had respiratory symptoms. All had received BCG vaccinations, and 46.15% had adverse post-vaccination reactions. Compared with Mycobacterium tuberculosis, BCG bacteremia was more likely to appear in younger children. Patients with BCG bacteremia had primary immunodeficiency diseases, and lower CD4, IgA, and IgE levels.Interpretation:Bacteremia TB was rapidly fatal in a large proportion of the immunodeficient children. Because classic findings may not be diagnostically specific, a high level of clinical suspicion is required, especially for patients with certain types of immunosuppression. Studies are needed to develop rapid diagnostic tests and to determine the value of empirical therapy in childhood bacteremia TB.

简介：基于实例分别在VisualBasic、VFP、HTML超文本、以及AUTHORWARE中阐述ActiveX控件的使用方法,充分展示其应用的广泛性与功能的强大性。

简介：Inanactivenetwork,userscaninsertcustomizedactivecodesintoactivenodestoexecute.Thusitneedsmoreresourcesthanthoserequiredbyconventionalnetworks,andtheseresourcesmustbeeffectivelymonitoredandmanaged.ManagementpoliciesinexistingOSsaretoocomplicatedtoapplytosimpleactivepackets.Inthispaper,wepresentnewresourcesmanagementpoliciesthataremainlyadopedtomanageCPU,storageandtransmissionbandwidth.Namely,weuseSPFalgorithmtoscheduleandprocessactivepackets,andimportanintervalqueuemethodtoallocatetransmissionbandwidth,andusefeedbackmechanismtocontrolcongestion.Atthesametime,wedesignsomeexperimentsonprototypesystemswithandwithoutresourcesmanagementpoliciesrespectively.Theexperimentsresultsshowthatmanagementpoliciespresentedbyuscaneffectivelymanageresourcesinactivenodesandcanimprovetheperformanceofactivenetworks.

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简介：Thetectonicmovementathumanscalehasnotbeenfullyunderstoodyet,especiallyforactivetectonics,althoughitisthebasistostudynaturalhazardsandenvironmentalvariations.Manynationalandinternationalscientificplansrelatedcloselytoactivetectonicsresearchhavebeenmadeinthepasttenyears.Thispaperbrieflysummarizedthebackgroundoftheundertakingofactivetectonicsresearch,itsadvancesandexistingproblems,andthekeypointsinitsfuturestudiesarealsopointedout.TheemergingofnewtechnologiesliketheEarthObservingSystem,DigitalSeismologyandsoonprovidesunusualopportunitiesfortectonicresearch.Itisemphasized,however,thatcarefulanalysesandbuildingupofnewtheoreticalframearesillthekeyproblemsforstudiesofactivetectonics,especiallyforactivetectonicsinChina'scontinent.

简介：Insteadofvision,manynocturnalanimalsusealternativesensesfornavigationandobjectdetectionintheirdarkenvi-ronment.Forthispurpose,weaklyelectricmormyridfishemployactiveelectrolocation,duringwhichtheydischargeaspe-cializedelectricorganintheirtailwhichdischargeselectricalpulses.Eachdischargebuildsupanelectricalfieldaroundthefish,whichissensedbycutaneouselectroreceptororgansthataredistributedovermostofthebodysurfaceofthefish.Nearbyobjectsdistortthiselectricalfieldandcausealocalalterationincurrentflowinthoseelectroreceptorsthatareclosesttotheobject.Byconstantlymonitoringresponsesofitselectroreceptororgans,afishcandetect,localize,andidentifyenvironmentalobjects.Inspiredbytheremarkablecapabilitiesofweaklyelectricfishindetectingandrecognizingobjects,wedesignedtechnicalsensorsystemsthatcansolvesimilarproblemsofremoteobjectsensing.Weappliedtheprinciplesofactiveelectrolocationtotechnicalsystemsbybuildingdevicesthatproduceelectricalcurrentpulsesinaconductingmedium(waterorionizedgases)andsimultaneouslysenselocalcurrentdensity.Dependingonthespecifictaskasensorwasdesignedfordevicescould(i)detectanobject,(ii)localizeitinspace,(iii)determineitsdistance,and(iv)measurepropertiessuchasmaterialproperties,thickness,ormaterialfaults.Oursystemsprovedtoberelativelyinsensitivetoenvironmentaldisturbancessuchasheat,pressure,orturbidity.Theyhaveawiderangeofapplicationsincludingmaterialidentification,qualitycontrol,non-contactdistancemeasurements,medicalapplicationsandmanymore.Despitetheirastonishingcapacities,oursensorsstilllagfarbehindwhatelectricfishareabletoachieveduringactiveelectrolocation.Theunderstandingoftheneuralprinciplesgoverningelectricfishsensoryphysi-ologyandthecorrespondingoptimizationofoursensorstosolvecertaintechnicaltasksthereforeremainongoinggoalsofourresearc

简介：AbstractBackground:Despite free diagnosis and treatment for tuberculosis (TB), the costs during treatment impose a significant financial burden on patients and their households. The study sought to identify the determinants for cata-strophic costs among patients with drug-sensitive TB (DSTB) and their households in Kenya.Methods:The data was collected during the 2017 Kenya national patient cost survey from a nationally representative sample (n= 1071). Treatment related costs and productivity losses were estimated. Total costs exceeding 20% of household income were defined as catastrophic and used as the outcome. Multivariable Poisson regression analysis was performed to measure the association between selected individual, household and disease characteristics and occurrence of catastrophic costs. A deterministic sensitivity analysis was carried using different thresholds and the significant predictors were explored.Results:The proportion of catastrophic costs among DSTB patients was 27% (n = 294). Patients with catastrophic costs had higher median productivity losses, 39 h [interquartile range (IQR): 20-104], and total median costs of USD 567 (IQR: 299-1144). The incidence of catastrophic costs had a dose response with household expenditure. The poorest quintile was 6.2 times [95% confidence intervals (CI): 4.0-9.7] more likely to incur catastrophic costs compared to the richest. The prevalence of catastrophic costs decreased with increasing household expenditure quintiles (proportion of catastrophic costs: 59.7%, 32.9%, 23.6%, 15.9%, and 9.5%) from the lowest quintile (Q1) to the highest quintile (Q5). Other determinants included hospitalization: prevalence ratio (PR)= 2.8 (95% CI: 1.8-4.5) and delayed treatment: PR = 1.5 (95% CI: 1.3-1.7). Protective factors included receiving care at a public health facility: PR = 0.8 (95% CI: 0.6-1.0), and a higher body mass index (BMI): PR= 0.97 (95% CI: 0.96-0.98). Pre TB expenditure, hospitalization and BMI were significant predictors in all sensitivity analysis scenarios.Conclusions:There are significant inequities in the occurrence of catastrophic costs. Social protection interventions in addition to existing medical and public health interventions are important to implement for patients most at risk of incurring catastrophic costs.

简介：AbstractBackground:Tuberculosis (TB) is a major global health threat and the leading infectious disease cause of death worldwide. Access to and retention in TB care remains a challenge for patients, particularly those living in rural and remote settings. This qualitative study explored barriers and facilitators to accessing and maintaining contact with TB care services in communities in Xigaze (Shigatse) prefecture, Xizang Autonomous Region (Tibet Autonomous Region), China from the perspective of persons impacted by TB.Methods:We conduced in-depth interviews with 23 participants impacted by TB in four rural districts in Xigaze prefecture, Xizang Autonomous Region, China between April 2019 and November 2020. Interviews were conducted in Tibetan and Mandarin, transcribed in Mandarin and translated into English. Transcripts were checked against recordings by native Tibetan and Mandarin speakers. QSR NVivo12 software was used for framework analysis guided by an access to care conceptual framework by Levesque et al.Results:Overall patients reported low awareness of and an indifferent attitude towards TB, although all reported understanding the need to adhere to treatment. Participants reported complex pathways to care, often requiring visits to multiple healthcare facilities. Some participants reported visiting traditional Tibetan medicine (TTM) providers. Participants reported various barriers to accessing care including challenges physically reaching care, out-of-pocket payments for tests, diagnostics and transport. Barriers to maintaining care included medication side effects and worry about treatment effectiveness. Enablers to accessing care identified included knowledge or past experience with TB, integrated models of TTM and western care, supportive village doctors who conducted home visits, free TB treatment and other subsidies, as well as having family support with care and social support as barriers and facilitators to maintaining treatment.Conclusions:We identified barriers and facilitators to accessing services in rural communities in Xigaze from the perspective of persons impacted by TB. Challenges include complex pathways to care, travel distances, wait times and low awareness. Tuberculosis care in the region could be strengthened by ongoing culturally tailored educational campaigns to increase awareness, partnerships with TTM providers, providing comprehensive treatment subsidies and strengthening the role of family members in comprehensive TB care.

简介：肺结核仍然是全球传染的疾病。识别M的治疗学的潜力。在对待肺结核的vaccae，M。vaccae被注入Mycobacterium肺结核(M。肺结核)感染的老鼠。M的最佳的剂量。对待的老鼠显示出的vaccae(22.5g/mouse)降低病理学的变化索引，怒气重量索引，肺重量索引和重要M。肺结核未经治疗的组比那些数。有M的治疗。vaccae提高了CD3+和CD4+T房间，IFN-+CD4+T房间，包括NK房间的天生的有免疫力的房间，NK1.1+T房间和T房间的百分比，并且减少了IL-4+CD4+T房间的百分比。因此，M。vaccae能保护老鼠免受M的伤害。肺结核感染和天生的改进老鼠和适应装壁板圩调停免疫，建议那M。vaccae是在肺的肺结核的一个潜在的immunotherapeutic代理人。

简介：Anoveltuberculosis(TB)genevaccinecontainingmousegranulocytemacrophage-colonystimulatingfactor(mGM-CSF)andaTBantigen(Ag85A)wasdevelopedinthisstudy.ThegenesencodingAg85AandmGM-CSFwereamplifiedbyPCRrespectivelyfromtheAg85A-containingpBSby5andpC-mGM-CSF.ThegeneswerethenclonedintotwodifferentpolylinkersitesofplasmidpIRES,forminganovelTBgenevaccineconstructpI85AGM.FollowingtransfectionofpI85AGMplasmidinto7721celllinebyLipofectamineTM,theexpressionofAg85AandGM-CSFproteinswasidentifiedbyWesternblottingorRT-PCR.ThenBalb/cmicewereinoculatedwiththerecombinantpI85AGM,pI85A,pIGMorplasmidalone,respectively.TheactivitiesofCTL,NKcellsandtheAg85A-stimulatedproliferationofspleencellsweremeasuredbyMTTmethod.TheserumantibodyagainstAg85AwasdetectedbyELISA.TheresultsshowedthattheAg85AandGM-CSFproteinscouldbeexpressedin7721celllineandtheactivityofCTLsandtheproliferationofspleencellsweresignificantlyincreasedinthepI85AGM-immunizedmice,indicatingthatthepI85AGM-immunizedmicecouldgeneratespecificimmuneresponsestoAg85A.Thisstudymightprovidepossibilityfordevelopingnovelanti-TBgenevaccine.