Population-based active screening strategy contributes to the prevention and control of tuberculosis.

Despite the achievements obtained worldwide in the control of tuberculosis in recent years, many countries and regions including China still face challenges such as low diagnosis rate, high missed diagnosis rate, and delayed diagnosis of the disease. The discovery strategy of tuberculosis in China has changed from "active discovery by X-ray examination" to "passive discovery by self-referral due to symptoms", and currently the approach is integrated involving self-referral due to symptoms, active screening, and physical examination. Active screening could help to identify early asymptomatic and untreated cases. With the development of molecular biology and artificial intelligence-assisted diagnosis technology, there are more options for active screening among the large-scale populations. Although the implementation cost of a population-based active screening strategy is high, it has great value in social benefits, and active screening in special populations can obtain better benefits. Active screening of tuberculosis is an important component of the disease control. It is suggested that active screening strategies should be optimized according to the specific conditions of the regions to ultimately ensure the benefit of the tuberculosis control.

Profiling T cell receptor ß-chain in responders after immunization with recombinant hepatitis B vaccine.

BACKGROUND: T cells with edited T cell receptor ß-chain variable (TRBV) are involved in the immune response to recombinant hepatitis B surface antigen (rHBsAg) vaccine and the production of hepatitis B surface antibody (HBsAb). The immune repertoire (IR) profile and mechanism of vaccination positive responders (VPR) with rHBsAg are not fully understood. METHODS: The IR of six VPRs (HBsAb+, HbsAg-) with rHBsAg vaccination was established by the high throughput sequencing technique and bioinformatics analysis and compared with those in five vaccination negative responders (VNRs) (HbsAb-, HbsAg-) who were also inoculated with rHBsAg. The repertoire features of the BV, BJ and V (CDR3) J genes and immune diversity in peripheral blood mononuclear cells, respectively, were analyzed for each subject. RESULTS: There was no significant difference in sequencing amplification indices of each sample. However, TRBV15/BJ2-3 demonstrated significantly high expression levels in VPR compared to those in the VNR group (both p < 0.05). Further results showed that the BV15/BJ2-5 level was significantly increased for VPR compared to that of VNR group. Interestingly, the motif of CDR3 in TRBV15/BJ2-5 was mostly expressed as "GGETQ" or "GETQ". Additionally, there was no remarkable difference between the two groups of distribution with respect to the different clone expression levels of V (CDR3) J. CONCLUSIONS: The features of IR in the VPR and VNR will contribute to the exploration of the mechanism of the positive response to rHBsAg, and also contribute to development of optimized hepatitis B vaccine, in addition to providing a partial interpretation of the VNR who has a relatively low infection with HBV.

Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates.

BACKGROUND: Tetrandrine is a natural chemical product purified from fourstamen stephania root which recently has been shown to act similarly as synthesized drug efflux pump inhibitor verapamil. The aim of the study is to examine whether tetrandrine could potentiate anti-tubercular drugs to which Mycobacterium tuberculosis (MTB) has turned resistant via efflux mechanisms. METHODS: We screened 200 MTB clinical isolates using drug sensitivity test to look for those who have turned resistant to the drugs most probably due to efflux mechanisms. We found 29 isoniazid (INH) and ethambutol (EMB) - dual resistant (IEDR) strains. Then we tested if treatment with tetrandrine or verapamil could reverse drug resistance to INH and/or EMB in IEDR isolates. RESULTS: There is a parallel resistance among EMB- and INH-resistant strains in the tested clinical isolates. Among INH-resistant strains, 65% was also EMB-resistant. This suggests an involvement of efflux mechanisms which can lead to dual drug resistance in IEDR clinical isolates. Similar to a synthesized efflux pump inhibitor verapamil, tetrandrine treatment together with INH or EMB brought down the MICs from the clinical level of drug resistance to the sensitive range of both drugs. The effective rate reached 82% among IEDR clinical isolates. CONCLUSIONS: Combinational application of tetrandrine with INH or EMB increased drug efficacy. Drugs like tetrandrine may help to reduce drug dosage thus alleviate side effects.

Clinical characteristics and antimicrobial susceptibility profiles of Mycobacterium abscessus and Mycobacterium massiliense pulmonary infection.

OBJECTIVES: Mycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug-susceptibility statuses of different M. abscessus (MAB) subspecies in the Zhejiang Province. METHODS: DNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine in vitro susceptibility of imipenem-relebactam (IMP-REL), omadacycline, and other conventional antibiotics. Patient clinical characteristics were collected and analysed. RESULTS: In total, 139 M. abscessus, 39 Mycobacterium massiliense, and 1 Mycobacterium bolletii isolates were collected, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. IMP-REL resulted in a twofold reduction in the minimum inhibitory concentration (MIC) value compared with imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. CONCLUSIONS: M.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. IMP-REL and omadacycline are promising antibiotics for MABC infection treatment.

Antimicrobial and Antibiofilm Effects of Bithionol against Mycobacterium abscessus.

Mycobacterium abscessus (M. abscessus) is a multidrug-resistant nontuberculous mycobacterium (NTM) that is responsible for a wide spectrum of infections in humans. The lack of effective bactericidal drugs and the formation of biofilm make its clinical treatment very difficult. The FDA-approved drug library containing 3048 marketed and pharmacopeial drugs or compounds was screened at 20 µM against M. abscessus type strain 19977 in 7H9 medium, and 62 hits with potential antimicrobial activity against M. abscessus were identified. Among them, bithionol, a clinically approved antiparasitic agent, showed excellent antibacterial activity and inhibited the growth of three different subtypes of M. abscessus from 0.625 µM to 2.5 µM. We confirmed the bactericidal activity of bithionol by the MBC/MIC ratio being ≤4 and the time-kill curve study and also electron microscopy study. Interestingly, it was found that at 128 µg/mL, bithionol could completely eliminate biofilms after 48h, demonstrating an outstanding antibiofilm capability compared to commonly used antibiotics. Additionally, bithionol could eliminate 99.9% of biofilm bacteria at 64 µg/mL, 99% at 32 µg/mL, and 90% at 16 µg/mL. Therefore, bithionol may be a potential candidate for the treatment of M. abscessus infections due to its significant antimicrobial and antibiofilm activities.

Psoralea corylifolia L. and its active component isobavachalcone demonstrate antibacterial activity against Mycobacterium abscessus.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. (Fabaceae) is a traditional medicinal herb used to treat various diseases, including kidney disease, asthma, psoriasis and vitiligo. AIM OF THE STUDY: To explore the antibacterial activity of Psoralea corylifolia L. and its bioactive components against Mycobacterium abscessus (M. abscessus). MATERIALS AND METHODS: Ultra high performance liquid chromatography was utilized to analyze the bioactive fractions and compounds present in 30%, 60%, and 90% ethanol extracts of Psoralea corylifolia L.. The antibacterial effects of Psoralea corylifolia L. and potential active ingredients were determined by minimum inhibitory concentration (MIC). The bactericidal activity of the active ingredient isobavachalcone was evaluated and then scanning electron microscopy was used to explore the bactericidal mechanism of isobavachalcone. RESULTS: The 90% ethanol extracts of Psoralea corylifolia L. showed significant antibacterial activity against M. abscessus, with an MIC of 156 µg/mL. Isobavachalcone was identified as the bioactive ingredient, and testing of 118 clinical isolates of M. abscessus indicated their MICs ranged from 2 to 16 µg/mL, with an average MIC of 8 µg/mL. Furthermore, the minimum bactericidal concentration/MIC ratio and the time-kill test indicated rapid bactericidal activity of isobavachalcone against M. abscessus. Finally, we found that the bactericidal mechanism of isobavachalcone involved damage to the bacterial cell membrane, causing wrinkled and sunken cell surface and a noticeable reduction in bacterial length. CONCLUSION: Psoralea corylifolia L. ethanol extracts as well as its active component isobavachalcone show promising antimicrobial activity against M. abscessus.

The Utility of Real-Time PCR, Metagenomic Next-Generation Sequencing, and Culture in Bronchoalveolar Lavage Fluid for Diagnosis of Pulmonary Aspergillosis.

Timely detection of Aspergillus infection is crucial given the high mortality rate of pulmonary aspergillosis (PA). Here, the diagnostic performances for PA of mycological culture, Aspergillus real-time PCR, and metagenomic next-generation sequencing (mNGS) assay from bronchoalveolar lavage fluid, were evaluated. In total, 139 patients with suspected fungal pneumonia were enrolled between December 2021 and July 2023, collecting 139 bronchoalveolar lavage fluid samples for real-time PCR and culture, with 87 undergoing mNGS assay. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve with 95% CIs of these assays for PA were as follows: 35.3% (14.2%-61.7%), 100.0% (94.0%-100.0%), 100.0% (54.1%-100.0%), 84.5% (79.3%-88.6%), and 0.676 (0.560-0.779), respectively, for culture; 82.4% (56.6%-96.2%), 98.3% (91.1%-100.0%), 93.3% (66.4%-99.0%), 95.2% (87.6%-98.2%), and 0.903 (0.815-0.959), respectively, for same diagnostic performance of real-time PCR and mNGS; and 94.1% (71.3%-99.9%), 96.7% (88.5%-99.6%), 88.9% (67.1%-96.9%), 98.3% (89.6%-99.7%), and 0.954 (0.880-0.989), respectively, for real-time PCR combining mNGS; real-time PCR, mNGS, and their combination significantly improved in area under the curve values over culture (P < 0.001), but real-time PCR testing and mNGS had no significant difference with each other and their combination. Overall, the performance of culture was limited by low sensitivity; both real-time PCR and mNGS assays as single diagnostic tests are promising compared with culture and combined tests.

Diagnostic Efficiency of the Blood-Based Cepheid 3-Gene Host Response Test and Urine-Based Lipoarabinomannan for Active Tuberculosis Case Detection at a General Hospital in China.

Objective: To assess the diagnostic performance of the blood-based Cepheid 3-gene Host Response test (MTB-HR), urine-based Lipoarabinomannan (LAM), and a combination of MTB-HR and LAM (MTB-HR & LAM) for detecting active tuberculosis (ATB). Methods: All participants were recruited from the First Affiliated Hospital, Zhejiang University School of Medicine, between June 8, 2023 and September 13, 2023. Subsequently, the participants were classified into the ATB group or non-active tuberculosis (non-ATB) group based on microbiological evidence. MTB-HR and LAM tests were performed using fingerstick blood and urine samples from each participant, respectively. The diagnostic performance of the tests was evaluated based on the sensitivity, specificity, Youden index, and Kappa value. Pairwise comparisons of the areas under the receiver operating characteristic curves (AUROCs) between different tests were conducted using nonparametric methods. Results: A total of 297 participants were included. The MTB-HR test demonstrated diagnostic efficacy with a sensitivity of 77.37% (95% CI: 70.37-84.38) and a specificity of 85.63% (95% CI: 80.19-91.06). The LAM test demonstrated a high specificity of 97.50% (95% CI: 95.08-99.92), albeit with a lower sensitivity of 54.74% (95% CI: 46.41-63.082). The sensitivity and specificity of the MTB-HR & LAM were 83.21% (95% CI: 76.95-89.47) and 83.13% (95% CI: 77.32-88.93), respectively. Only MTB-HR & LAM exhibited higher values of area under the receiver operating characteristic curve than the LAM test (MTB-HR & LAM vs LAM: 0.83 vs 0.76, P=0.0031). Conclusion: In this study, although both non-sputum-based triage MTB-HR and LAM do not meet the WHO diagnostic target currently, they show possible values for triage and diagnosis in ATB. Compared to single MTB-HR or LAM test, the combined MTB-HR & LAM does not demonstrate advantages.

Molecular characterization of T cell receptor beta variable in the peripheral blood T cell repertoire in subjects with active tuberculosis or latent tuberculosis infection.

BACKGROUND: T cells are closely linked to the clinical manifestations of subjects with Mycobacterium tuberculosis (MTB) infection. T cell receptor beta variable (TCRBV) is a signal and indicative molecule on the membrane of T lymphocytes, reflecting the composition and specificity of T cells. The molecular profiles of TCRBV in peripheral blood mononuclear cells (PBMCs) and their subpopulations (CD4+ and CD8+ T cells) from subjects with active tuberculosis (TB) or latent TB infection (LTBI) have not been well described. METHODS: In 42 subjects with active TB or LTBI, PMBCs and their subsets were separated and sorted. The molecular profiles of the TCRBV complementarity determining region 3 (CDR3) in the three cell populations were investigated using our recently developed gene melting spectral pattern (GMSP) assay. The TCRBV members were then cloned and sequenced when their GMSP image profiles showed a single-peak. RESULTS: The average number of skewed TCRBV molecules in the CD4+ cell subset was significantly higher than that in PBMCs and CD8+ T cells. TCRBV12, BV13.1, BV13.2, and BV24 were expressed more prevalently than other TCRBV gene families in the three cell populations. In addition, relatively conserved amino acid motifs were identified in TCRBV5.1 and BV20 CDR3 in PBMCs and its subsets. The monoclonal TCRBV14 and BV23 expressed were different between active TB and LTBI subjects. CONCLUSIONS: These results indicate that the T cell immune response is complex and multi-specific in active TB and LTBI subjects. Analysis of TCRBV expression in CD4+ T cells suggest that it could be useful in assessing the composition and status of circulating T cells. Furthermore, the expression of TCRBV14, BV23 and the sequencing of CDR3 amino acid motifs of TCRBV5.1, BV20 could be used in the differential diagnosis and treatment of subjects with active TB or LTBI.

Resynchronized rhythmic oscillations of gut microbiota drive time-restricted feeding induced nonalcoholic steatohepatitis alleviation.

With the drive of the endogenous circadian clock and external cues such as feeding behavior, the microbial community generates rhythmic oscillations in composition and function. Microbial oscillations are crucial in orchestrating host metabolic homeostasis during the predictable 24-hour diurnal cycle. A time-restricted feeding (TRF) regimen is a promising dietary strategy to optimize energy utilization, alleviate metabolic syndrome and reinforce microbial cyclical fluctuations. However, the causative relationship between reinforced microbial rhythmicity and TRF-induced metabolic improvement remains elusive. In this study, we corroborated that the TRF regimen notably alleviated obesity and nonalcoholic steatohepatitis (NASH) with reinstated rhythmicity of genera such as Lactobacillus, Mucispirillum, Acetatifactor, and Lachnoclostridium. The reshaped microbial oscillations correlate with cyclical fluctuations in intestinal amino acids. Furthermore, fecal microbiota transplantation (FMT) indicated that only the TRF feeding phase-derived microbiota, but not the TRF fasting phase-derived microbiota, could protect mice from NASH and reinstate microbial rhythmicity, confirming that the microbiota improved NASH in a time-of-day-specific manner. The unique role of the TRF-feeding phase-derived microbiota was accompanied by regulation of the serotonergic synapse pathway and rejuvenation of the microbial production of indole derivatives. Our results revealed the discrepant characteristics between the feeding and fasting phases and the time-of-day-specific configuration of microbiota functionality in the TRF regimen.

Randomized control study of the use of faropenem for treating patients with pulmonary tuberculosis.

OBJECTIVES: Faropenem has antituberculosis activity in vitro but its utility in treating patients with tuberculosis (TB) is unclear. METHODS: We conducted an open-label, randomized trial in China, involving newly diagnosed, drug-susceptible pulmonary TB. The control group was treated with the standard 6-month regimen. The experimental group replaced ethambutol with faropenem for 2 months. The primary outcome was the treatment success rate after 6 months of treatment. Noninferiority was confirmed if the lower limit of a 95% one-sided confidence interval (CI) of the difference was greater than -10%. RESULTS: A total of 227 patients eligible for the study were enrolled in the trial group and the control group in a ratio of 1:1. Baseline characteristics of participants were similar in both groups. In the modified intention-to-treat population, 88.18% of patients in the faropenem group achieved treatment success, and 85.98% of those in the control group were successfully treated, with a difference of 2.2% (95% CI, -6.73-11.13). In the per-protocol population, treatment success was 96.04% in the faropenem group and 95.83% in the control group, with a difference of 2.1% (95% CI, -5.31-5.72). The faropenem group showed noninferiority to the control group in the 6-month treatment success rates. The faropenem group had significantly fewer adverse events (P <0.01). CONCLUSIONS: Our study proved that oral faropenem regimen can be used for the treatment of TB, with fewer adverse events. (Chinese Clinical Trial Registry, ChiCTR1800015959).

Epidemic of Klebsiella pneumoniae ST11 clone coproducing KPC-2 and 16S rRNA methylase RmtB in a Chinese University Hospital.

BACKGROUND: Emergence of rmtB-positive Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) poses a great threat to antimicrobial treatment options. METHODS: From January 2010 to December 2010, non-duplicate KPC-KP isolates from our hospital were screened for rmtB and multiple other resistance determinants with PCR. Subsequent studies included MIC determination, PFGE, and multilocus sequence typing. Records from patients with KPC-KP isolated were retrospectively reviewed. Comparisons of molecular and clinical characteristics between rmtB-positive and rmtB-negative isolates were systematically performed, as well as the environmental colonization study in ICU wards. RESULTS: A total of 84 KPC-KP strains were collected, including 48 rmtB-positive KPC-KP (RPKP) and 36 rmtB-negative KPC-KP (RNKP) isolates. All KPC-KP isolates were multidrug resistant, with colistin and tigecycline being the most active agents. Compared with RNKP, RPKP displayed a much severer resistance phenotype. Susceptibility rates for amikacin (0% for RPKP versus 88.9% for RNKP, p < 0.01), fosfomycin (8.5% for RPKP versus 88.9% for RNKP, p < 0.01), and minocycline (6.7% for RPKP versus 52.8% for RNKP, p < 0.01), were all significantly lower in RPKP strains. Isolates belonging to PFGE pulsetype A and sequence type 11 were predominant in both groups, including 39 (81.3%) RPKP and 22 (61.1%) RNKP isolates. Nevertheless, RNKP showed more complex genetic backgrounds compared with RPKP. Diverse clinical characteristics were found in both cohorts, however, no significant differences were observed between RPKP and RNKP patients. CONCLUSIONS: RPKP strains have spread widely and gradually replaced RNKP in our hospital. They seemed to show much severer resistance phenotypes compared with RNKP and had a bigger dissemination potential. Prudent use of available active agents combined with good control practices is therefore mandatory.

Oral Bacteria Dysbiosis in Patients with Linezolid-Induced Black Hairy Tongue: A Case Series.

Linezolid-induced black hairy tongue is a self-limiting benign disease that is rare. Here, we report three patients who developed black hairy tongue after linezolid treatment. The severe dysbiosis of oral bacterial communities was observed in all these patients. Proteobacteria was the most prevalent phylum (over 90%) at the black tongue stage. Furthermore, the dramatic oral bacterial alteration took a long time to reverse after the BHT resolved.

Characteristic gut microbiota and metabolic changes in patients with pulmonary tuberculosis.

Intestinal flora provides an important contribution to the development of pulmonary tuberculosis (PTB). We performed a cross-sectional study in 52 healthy controls (HCs) and 83 patients with untreated active PTB to assess the differences in their microbiomic and metabolic profiles in faeces via V3-V4 16S rRNA gene sequencing and gas chromatography-mass spectrometry. Patients with PTB had considerable reductions in phylogenetic alpha diversity and the production of short-chain fatty acids, dysbiosis of the intestinal flora and alterations in the faecal metabolomics composition compared with HCs. Significant alterations in faecal metabolites were associated with changes in the relative abundance of specific genera. Our study describes the imbalance of the gut microbiota and altered faecal metabolomics profiles in patients with PTB; the results indicate that the gut microbiota and faecal metabolomic profiles can be used as potential preventive and therapeutic targets for PTB.

Role and characteristics of hippocampal region microglial activation in poststroke depression.

AIMS: To study the role and characteristics of activated microglia in poststroke depression (PSD) . METHODS: Twenty-four male Wistar rats were randomly divided into three groups: the poststroke (PS) group, PSD group, and Sham group. Neurobehavioral testing was performed 24 h postoperation. The body weights of the rats were regularly recorded, and behavioral testing was regularly performed at 1, 2 and 3 weeks postmodeling. Immunofluorescent staining was used to detect the microglial marker OX42. Real-time PCR was used to analyze the relative gene expression of microglial activation markers (TNF-a, IL-10, IL-1, TGF-ß, CD86, iNOS, CD206, IL-1ß, and Arg1) . RESULTS: The relative gene expression of proinflammatory markers (IL-1, TNF-a, iNOS, and IL1ß) and anti-inflammatory markers (CD206 and Arg1) significantly increased in the hippocampal region compared with that in the right cerebral and left cerebral hemispheres in the PSD group. The relative gene expression of proinflammatory markers (TNF-a, IL-1, iNOS, and CD86) in the hippocampal region was significantly increased in the PSD group compared with that in the Sham and PS groups. The anti-inflammatory markers (TGF-ß and CD206) in the hippocampal region were significantly increased in the PSD group compared with that in the Sham group, and the M2 marker Arg1 was significantly increased in the PSD group compared with that in the PS group. Correlation analysis showed that IL-1 was strongly negatively correlated with PSD . CONCLUSIONS: Most microglia in the hippocampal region of PSD had a proinflammatory status and an anti-inflammatory status. IL-1 showed a strong negative correlation with PSD.

Cytokine Signature Associated With Disease Severity in COVID-19.

Coronavirus disease 2019 (COVID-19) broke out and then became a global epidemic at the end of 2019. With the increasing number of deaths, early identification of disease severity and interpretation of pathogenesis are very important. Aiming to identify biomarkers for disease severity and progression of COVID-19, 75 COVID-19 patients, 34 healthy controls and 23 patients with pandemic influenza A(H1N1) were recruited in this study. Using liquid chip technology, 48 cytokines and chemokines were examined, among which 33 were significantly elevated in COVID-19 patients compared with healthy controls. HGF and IL-1ß were strongly associated with APACHE II score in the first week after disease onset. IP-10, HGF and IL-10 were correlated positively with virus titers. Cytokines were significantly correlated with creatinine, troponin I, international normalized ratio and procalcitonin within two weeks after disease onset. Univariate analyses were carried out, and 6 cytokines including G-CSF, HGF, IL-10, IL-18, M-CSF and SCGF-ß were found to be associated with the severity of COVID-19. 11 kinds of cytokines could predict the severity of COVID-19, among which IP-10 and M-CSF were excellent predictors for disease severity. In conclusion, the levels of cytokines in COVID-19 were significantly correlated with the severity of the disease in the early stage, and serum cytokines could be used as warning indicators of the severity and progression of COVID-19. Early stratification of disease and intervention to reduce hypercytokinaemia may improve the prognosis of COVID-19 patients.

Risk factors for negative T-SPOT.TB assay results in patients with confirmed active tuberculosis: A retrospective study.

INTRODUCTION: The interferon-γ release assays as potent adjunct tools for the quick detection of TB in high burden countries is feasible. In this retrospective study, we aimed to identify the risk factors for negative T-SPOT results in confirmed active tuberculosis. METHODOLOGY: We consecutively enrolled 1,021 patients who were positive for acid-fast bacilli smear staining or culture-confirmed mycobacterial infection and simultaneously tested with the T-SPOT.TB assay. All of the included specimens were used to discriminate the Mycobacterium species using the biochip assay. We collected basic clinical characteristics and laboratory results for further analysis. RESULTS: Of the 1,021 patients enrolled in the study, 89 patients were identified as having nontuberculous mycobacteria (NTM). Ninety-nine patients were excluded from the analysis because of indeterminate T-SPOT.TB results, while the remaining 833 patients were identified as having Mycobacterium tuberculosis infection. In total, 159 patients had false-negative T-SPOT.TB results (19.1% of 833). The concordance rate between the T-SPOT.TB results and final diagnoses in females was always lower than that in males. Multivariate logistic regression analysis showed that female sex (OR 1.81; 95% CI 1.19, 2.7; p = 0.006), age (OR 1.02; 95% CI 1.01, 1.03; p = 0.003), acid-fast bacilli (AFB) smear-negative (OR 5.45; 95% CI 3.62, 8.19; p < 0.001), HIV coinfection (OR 6.83; 95% CI 2.73, 17.10; p < 0.001) were associated with negative T-SPOT.TB result. CONCLUSIONS: Female is another independent risk factor of negative T-SPOT.TB results, besides to elder, HIV co-infection, acid-fast bacilli (AFB) smear-negative who are suspected of having active TB infection.

Epidemic Trends of Tuberculosis in China from 1990 to 2017: Evidence from the Global Burden of Disease Study.

PURPOSE: Tuberculosis remains a major public health problem globally, especially in undeveloped countries. This study aimed to evaluate and review the long-term epidemic trends of tuberculosis in China. METHODS: Data were extracted from the Global Health Data Exchange. Metrics (prevalence, incidence and mortality) and Joinpoint regression were used to identify the epidemic trends. RESULTS: From 1990 to 2017, decreasing trends in prevalence (average annual percent change, AAPC: -0.5%, 95% CI: -0.6% to -0.5%), incidence (-3.2%, 95% CI: -3.5% to -2.9%), and mortality (-5.7%, 95% CI: -6.2% to -5.3%) of tuberculosis were observed. The incidence and mortality of multidrug-resistant tuberculosis (MDR-TB) decreased with AAPC of -2.3% (-3.1% to -1.4%) and -4.9% (-5.4% to -4.5%), respectively, while the prevalence increased with an AAPC of 1.2% (0.3% to 2.0%). The burden of extensively drug-resistant tuberculosis (XDR-TB) increased with an AAPC of 12.5% (11.9% to 13.2%) in prevalence, 7.6% (6.5% to 8.7%) in incidence, and 4.5% (3.6% to 5.4%) in mortality. The disease burden of tuberculosis increased with age and peaked among those aged over 70. CONCLUSION: The epidemic of tuberculosis decreased in China, while the disease burden was still challenging to control. MDR-TB and XDR-TB should be emphasized along with the epidemic. It will certainly be a difficult task to achieve the post-2015 global targets by 2025 and 2035.

Profiling the mRNA and miRNA in Peripheral Blood Mononuclear Cells in Subjects with Active Tuberculosis.

PURPOSE: To identify candidate hub genes and miRNAs associated with active tuberculosis (ATB) and reveal the potential molecular mechanisms of disease progression. PATIENTS AND METHODS: The expression of mRNA and miRNA was evaluated in peripheral blood mononuclear cells (PBMC) from 4 ATB patients and 4 healthy donors (HD) using high throughput sequencing (HTS) and bioinformatics analysis. Moreover, differentially expressed miRNAs were validated with 35 ATB patients and 35 HDs using reverse transcription quantitative real-time PCR (RT-qPCR). RESULTS: A total of 2658 significantly differentially expressed genes (DEG) including 1415 up-regulated genes and 1243 down-regulated genes were identified in the ATB group compared with HDs, and the DEGs enriched in immune-related pathways, especially in TNF signaling pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathways and tuberculosis. Additionally, 10 hub genes were acquired according to protein-protein interaction (PPI) analysis of DEGs. Moreover, 26 differentially expressed miRNAs were found in ATB group compared with HDs. Furthermore, RT-qPCR results showed that hsa-miR-23a-5p (P=0.0106), hsa-miR-183-5p (P=0.0027), hsa-miR-193a-5p (P=0.0021) and hsa-miR-941(P=0.0001) were significantly increased in the ATB patients compared with HD group, and the hsa-miR-16-1-3p was significantly decreased (P=0.0032). CONCLUSION: Our research provided a characteristic profile of mRNAs and miRNAs expressed in ATB subjects, and 10 hub genes related with ATB were found, which will contribute to explore the role of miRNAs and hub genes in the pathogenesis of ATB, and improve the ability of differential diagnosis and treatment for the disease.