Low-dose computed tomography (LDCT) is an effective screening tool for early lung cancer detection; however, it frequently reveals incidental findings (IFs) beyond suspicious pulmonary nodules. We conducted a multicenter observational analysis using data from a community-based, non-risk-stratified mobile LDCT screening program implemented across ten screening regions in China between August 2024 and December 2025. Participants aged ≥50 years completed a structured questionnaire and underwent LDCT screening. IFs were classified into pulmonary, cardiovascular, and extra-pulmonary domains and further categorized as non-actionable, potentially actionable, or actionable. Among 39,910 participants, Lung-RADS IV findings were detected in 697 participants (1.75%). Overall, 37,994 participants (95.20%) had at least one IF, including 28,581 (71.61%) with pulmonary IFs, 27,639 (69.25%) with cardiovascular IFs, and 21,278 (53.31%) with extra-pulmonary IFs. Frequent findings included pulmonary infectious or inflammatory abnormalities, emphysema, aortic or pulmonary artery abnormalities, coronary artery calcification, and liver and kidney/urinary abnormalities. In multivariable analyses, Lung-RADS IV status was associated with extra-pulmonary IFs, potentially actionable IFs, and potentially actionable or actionable IFs, but not with overall IF occurrence or actionable IFs alone. Standardized, actionability-based reporting and management pathways are needed to maximize clinical value while minimizing unnecessary follow-up and healthcare burden.

IntroductionBedaquiline (BDQ) is recommended in China as component of oral short-course regimens (SCR) for MDR-TB patients. However, the efficacy and safety of BDQ containing oral SCRs remain insufficiently validated in large-scale, well-designed clinical trials involving the Chinese population.MethodsA randomized, non-inferiority, open-label trial was conducted at 17 hospital clinics in China, enrolling adult patients with MDR-TB. Participants were assigned in a 1:1 ratio to receive either a 40-week oral BDQ-containing SCR or a 40-week oral non BDQ-containing SCR. The primary endpoint was the proportion of participants achieving favorable outcome at the end of treatment. The non-inferiority margin of the difference in proportion between the BDQ and control groups in the modified intent-to-treat (mITT) population was set at -15%.ResultsA total of 217 participants were randomized. Among 182 patients in the mITT population, the BDQ-containing SCR group achieved an 80.0% favorable outcome compared to 59.8% in the non-BDQ group, with an adjusted difference of 22.27% (95% CI 9.41-35.13%). BDQ-containing SCR was also associated with higher proportions of modified favorable outcomes and cure rates. Additionally, BDQ-containing SCR resulted in a higher culture conversion rate at the end of treatment and a shorter time to culture conversion. Serious adverse events occurred in 16 of 110 participants (14.5%) in the BDQ-containing SCR group and 25 of 107 participants (23.4%) in the non-BDQ-containing SCR group.Conclusion40-week BDQ-SCR proved non-inferior and superior, safe, and well tolerated in Chinese patients with MDR-TB. Further investigation into the long-term safety and efficacy of the BDQ-containing regimen is still needed in China. ClinicalTrials.gov NCT05306223. Prospectively registered on 16 March 2022.

Drug-resistant tuberculosis (DR-TB) remains a formidable public health challenge, posing a significant threat to human life and health security. Comprehensive comparative evidence on the efficacy and safety of various DR-TB treatment strategies remains limited. This study aimed to systematically evaluate and compare the effectiveness of different DR-TB treatment regimens and to assess their safety profiles based on the frequency of adverse events and drug-specific reactions. We systematically searched PubMed, Web of Science, and Embase for relevant studies published between 2006 and 2025. Data on drug-resistant tuberculosis and treatment regimens were extracted. Pooled rates and odds ratios (ORs) with 95

Background:Asthma remains a substantial public health burden in the United States, warranting updated estimates of prevalence, morbidity, and medication use across population subgroups. Methods:This study analyzed data from 114,505 participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2023. Asthma status (lifetime, current, attack, emergency visit) and medication use were assessed through self-reports and prescription data. Weighted prevalence trends were evaluated across demographic subgroups. Results:Among 114,505 participants (median age 37 years; 51.2% male) in NHANES 1999-2023, the prevalence of lifetime and current asthma was 14.7% and 8.8%, respectively. Lifetime asthma prevalence increased from 11.2% to 15.8%, and current asthma from 6.5% to 9.3%, by 0.41% (95%CI: 0.28 to 0.54) and 0.24% (0.09-0.38) per NHANES cycle, respectively. Prevalence was consistently higher in women, non-Hispanic Black individuals, and those with lower socioeconomic status. Adolescents had the highest lifetime asthma prevalence (19.3%). Asthma attacks and emergency visits among those with current asthma declined significantly, by -0.99% (-1.94 to -0.03) and -1.94% (-2.96 to -0.93) per NHANES cycle, respectively. During the study period, the prevalence of asthma medication use showed a biphasic trend: an overall increase from 1999 to 2000 to a peak in 2007-2008, followed by a significant decline through 2020-2023. Lower education and income levels were associated with higher medication usage. Conclusion:Over the past 2 decades, asthma prevalence increased at the population level, whereas the prevalence of asthma attacks and asthma-related emergency visits among individuals with current asthma declined.

Background Concern has been growing regarding tuberculosis (TB) morbidities, including neurologic and vascular comorbidities. The impact of dementia on the occurrence and progression of pulmonary tuberculosis (PTB) remains unclear. This study aimed to describe the risk factors associated with in-hospital mortality in patients with PTB and comorbid dementia. Methods This retrospective study consecutively enrolled 152 patients with PTB complicated by dementia admitted to Beijing Chest Hospital, Capital Medical University, from January 2015 to December 2025. In addition, 110 PTB patients without dementia were randomly selected as the control group. General demographic characteristics, clinical symptoms, laboratory test results, and other relevant data were collected. Multivariate logistic regression analysis was performed to identify risk factors associated with dementia in PTB. PTB with dementia were further divided into severe group (n = 66) and mild group (n = 86) based on disease progression during hospitalization. Univariate and multivariate logistic regression analyses were used to identify risk factors for severe disease in PTB with dementia. According to the 60-day outcome after admission, the dementia group was divided into survival group (n = 133) and death group (n = 19). LASSO regression was used for variable selection, and the selected variables were then included in a multivariate Cox regression model to analyze factors associated with mortality. Results Among the 152 patients with tuberculosis complicated by dementia, 133 survived and 19 died, with a case fatality rate of 12.5%. Multivariate logistic regression analysis showed that age, albumin (ALB), D-dimer, and neutrophil-to-lymphocyte ratio (NLR) were independent risk factors for dementia in PTB, with odds ratios (ORs) and 95% confidence intervals (CIs) of 1.098 (1.045–1.153), 0.700 (0.584–0.840), 1.537 (1.119–2.112), and 1.438 (1.121–1.845), respectively. Blood urea nitrogen (BUN) and D-dimer were independent risk factors for progression to severe disease in PTB patients with dementia, with ORs and 95% CIs of 1.198 (1.006–1.425) and 1.274 (1.026–1.583), respectively. LASSO and multivariate Cox regression analyses showed that NLR (hazard ratio [HR] = 1.030, 95% CI: 1.007–1.053) and D-dimer (HR = 2.796, 95% CI: 1.180–6.622) were significantly associated with mortality, increasing the risk of death in these patients. Conclusion Advanced age, low ALB, elevated D-dimer, and elevated NLR were independent risk factors for dementia in PTB patients. BUN and D-dimer were independent risk factors for progression to severe disease in PTB patients with dementia. Both NLR and D-dimer significantly increased the risk of mortality in these patients.

BACKGROUND:The diagnosis of pulmonary tuberculosis (TB) remains challenging in sputum-scarce and sputum-negative patients. Tongue swabs represent a promising noninvasive alternative specimen type that could overcome this diagnostic limitation. This study aimed to evaluate the performance of molecular detection of Mycobacterium tuberculosis (Mtb) from tongue swabs in this clinically challenging population. METHODS:In this study, we enrolled 625 sputum-scarce individuals with presumptive TB from 4 Chinese TB hospitals. For each participant, paired tongue swab and bronchoalveolar lavage fluid (BALF) specimens were collected. Tongue swab specimens were analyzed using MTB-specific PCR assay, while BALF specimens underwent comprehensive evaluation using both microbiological reference standard (MRS) and Xpert MTB/RIF assay. RESULTS:Tongue swab testing demonstrated high diagnostic accuracy with 79.9% sensitivity (95% CI: 73.9-84.8) and 99.5% specificity (95% CI: 98.0-99.9) against the MRS, and 81.7% sensitivity (95% CI: 75.7-86.6) with 97.6% specificity (95% CI: 95.5-98.8) against Xpert MTB/RIF. Notably, simulation modeling revealed that when the proportion of sputum-scarce patients exceeded 10%, the tongue swab PCR strategy outperformed conventional sputum-only Xpert MTB/RIF testing in overall case detection rates. CONCLUSIONS:Tongue swab-based PCR represents a noninvasive, accurate, and highly specific diagnostic approach for tuberculosis, particularly in sputum-scarce or sputum-negative individuals. While this study demonstrates its superior performance in such populations, further optimization of sampling protocols and molecular assays is needed to improve detection sensitivity in cases with low bacillary loads. Integrating tongue swab testing into routine TB diagnostic algorithms could enhance case detection, strengthen drug resistance surveillance, and contribute to reducing transmission.

In this study, TiCu cladding layers were fabricated on the surface of TC17 titanium alloy by electron-beam cladding (EB cladding) using preplaced TiCu powder mixtures with nominal Cu contents of 0.5, 1, 2, 5, and 10 wt%, aiming to reveal the regulating effect of Cu content on the microstructural evolution and service performance of the cladding layers. Microstructural analysis showed that all TiCu cladding layers were mainly composed of α'-Ti and β-Ti. With increasing Cu content, the β-stabilizing effect became more pronounced, resulting in an increased β-Ti content in the cladding layers. The overall microstructure exhibited a transition from a fine interlaced lamellar morphology to a wider lamellar morphology. Representative EBSD and TEM characterization of the Ti–10 wt% Cu cladding layer further confirmed the coexistence of α'-Ti and β-Ti and revealed high-density dislocation structures. TEM-EDS analysis showed that Cu was generally dispersed within the observed region, with a tendency for relative enrichment in β-Ti regions. The property tests showed that increasing Cu content increased the hardness and reduced the wear rate of the TiCu cladding layers. When the Cu content was 10 wt%, the cladding layer reached the highest hardness of 7.10 GPa, and the wear rate decreased to the lowest value of 1.74 × 10−4 mm3/(N·m). Unlike the trends in hardness and wear resistance, the corrosion resistance of the TiCu cladding layers did not continuously improve with increasing Cu content. Among them, the Ti–1 wt% Cu cladding layer exhibited the lowest corrosion current density (Icorr) of 2.10 × 10−9 A/cm2, showing the best corrosion resistance. These results establish a Cu-dependent composition–microstructure–property relationship under rapid EB solidification, revealing that higher Cu contents favor mechanical strengthening and wear resistance, whereas moderate Cu addition benefits corrosion resistance, thereby providing a mechanistic basis for tailoring TiCu EB-cladded layers to different surface-service requirements.

Background: Tuberculosis remains a major global public health challenge, particularly among children. This study aims to provide a comprehensive assessment of the global, regional, and national burden of tuberculosis among children (0-14 years) using data from the Global Burden of Disease (GBD) 2021 study. Methods: Data on the incidence of tuberculosis (drug-susceptible, MDR-TB, and XDR-TB), as well as disability-adjusted life years (DALYs), among children aged 0-14 years in 204 countries and territories from 1990 to 2021 were obtained from the GBD 2021 study. Estimated annual percentage changes (EAPCs) in age-standardised incidence rates (ASIRs) and DALY rate were calculated overall and stratified by age, sex, and sociodemographic index (SDI) to quantify temporal trends. Spearman correlation analyses were performed to assess associations between tuberculosis burden and SDI. Results: In 2021, there were an estimated 759,300 new tuberculosis cases (ASIR: 37.7 per 100,000 population) among children globally, including 32,515 cases of MDR-TB (ASIR: 1.6) and 1193 cases of XDR-TB (ASIR: 0.1). Both global ASIR and DALY rate exhibited a declining trend from 1990 to 2021, with EAPC of -2.61% (95%CI: -2.74 to -2.47) and -4.38% (-4.61 to -4.14), respectively. From 1990 to 2021, High-income North America was the only GBD region with an increasing ASIR for tuberculosis (EAPC = 1.12, 95% CI: 0.61 to 1.64). From 1990 to 2021, there was no significant change in ASIR of MDR-TB (EAPC = 1.18, 95% CI: -0.16 to 2.54). However, eight of the 21 GBD regions exhibited increasing trends in the ASIR of MDR-TB, with the largest increase observed in Oceania (11.99, 10.49 to 13.52), followed by Central Asia (9.76, 6.48 to 13.13) and South Asia (5.71, 3.10 to 8.38). A strong negative correlation was observed between tuberculosis burden and SDI, with the highest disease burden concentrated in low-SDI regions. Conclusions: Achieving elimination targets will require stronger diagnostics and treatment for childhood tuberculosis, alongside reduced transmission, improved infection detection, and preventive therapy for exposed children, especially those under 5 years.

Tuberculosis (TB) remains a major global health challenge. The close relationship between the microbiome and the host is becoming increasingly notable. While studies on the respiratory microbiome in pulmonary tuberculosis (PTB) exist, a comprehensive understanding of microbial characteristics across the entire respiratory tract is still lacking. To address this, we conducted a meta-analysis by integrating data from common and representative respiratory samples. We integrated 16S rRNA data from 11 public datasets encompassing upper respiratory tract specimens (URTs), sputum, and bronchoalveolar lavage fluid (BALF). Ecological patterns were investigated through co-occurrence networks and neutral community modeling, while taxonomic and functional analyses were conducted with QIIME2 and PICRUSt2. The respiratory microbiota in PTB exhibited dynamic variations while sharing common genera, such as Streptococcus, Prevotella, Veillonella, and Neisseria. Alpha diversity was consistently higher in PTB than in healthy controls, with BALF exhibiting the greatest microbial diversity. Several differentially abundant genera were identified among the three sample types, Serratia being almost exclusively detected in BALF. Notably, the microbial interaction network in sputum was more complex and demonstrated the best fit to the neutral community model. Functional predictions highlighted enriched pathways such as peptidoglycan maturation and ABC transporters, and Bacillus was linked to multiple metabolic pathways. Several KO functions were predicted to be more active in URTs and sputum than in BALF. Our multi-scale analysis delineates a niche-specific biogeography of the respiratory microbiome in PTB. By elucidating community assembly and microbe interplay, we position the respiratory microbiota as an active contributor to TB. This work paves the way for novel microbiota-based diagnostics and ecologically informed therapies. IMPORTANCE:Pulmonary tuberculosis (PTB) remains a leading cause of global mortality, yet the ecological principles shaping its respiratory microbiome are poorly understood. By integrating 16S rRNA datasets from upper and lower airway specimens, this study provides the first comprehensive meta-analysis of respiratory microbial diversity and function in PTB. We reveal distinct community structures and functional potentials among upper airways, sputum, and bronchoalveolar lavage fluid, driven by niche-specific ecological processes rather than stochastic assembly. These findings establish a baseline framework for interpreting microbial biogeography across the respiratory tract and highlight potential microbial biomarkers for site-specific monitoring and therapeutic targeting in PTB.

Background:Treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) faces severe challenges, including prolonged courses, marked drug toxicity, and poor patient compliance. While regimens containing new drugs (bedaquiline, delamanid) have substantially improved MDR/RR-TB outcomes, systematic research on the epidemiological characteristics and risk control of adverse drug reactions (ADRs) remains insufficient. This study, based on a national multi-center clinical cohort, retrospectively analyzed data from 2,151 patients, aiming to explore the characteristics and risk factors related to ADR and provide a basis for individualized treatment. Methods:This study retrospectively included 2,151 patients with MDR/RR-TB from two national multicenter clinical cohorts in China (including the bedaquiline cohort and the delamanid cohort) from 2017 to 2022. Clinical data were extracted using a standardized process, and patients with missing key data that could not be traced were excluded from the study. Adverse reactions were defined and graded. Potential risk factors were screened through univariate analysis (Chi-squared test), and independent risk factors for ADRs were identified using a multivariate logistic regression model. The association between different types of ADRs and treatment drugs was also analyzed. Results:Overall ADR incidence was 56.2% (62.2% in bedaquiline cohort vs. 45.7% in delamanid cohort). The most common ADRs were cardiovascular [29.1%, mainly corrected QT interval (QTc) prolongation], hepatic (20.9%), and hematological (12.6%). Independent risk factors included female sex [odds ratio (OR) =1.26], age ≥35 years (OR =1.31), body mass index <18.5 kg/m2 (OR =1.22), diabetes (OR =1.28), retreatment (OR =1.28), extrapulmonary TB (OR =1.62), cavitation (OR =1.24), and pre-extensively drug-resistant (XDR)/XDR-TB (OR =1.14/1.29). Both drugs were linked to QTc prolongation. Conclusions:New MDR/RR-TB regimens are effective but carry a high ADR burden. Enhanced monitoring of high-risk groups and QTc/liver function is essential.

Purpose:Limited evidence exists regarding impacts of prolonged bedaquiline use in the treatment of multidrug-resistant (MDR) tuberculosis (TB). This study evaluated the effectiveness and safety of prolonged bedaquiline use (>24 weeks) compared to the standard 24-week in MDR/extensively drug-resistant (XDR)-TB treatment with longer regimen. Patients and Methods:This retrospective study analysed a prospective cohort of drug-resistant pulmonary TB patients treated with bedaquiline provided by the Global Drug Facility in China. Patients were enrolled from February 2018 to April 2020 across 21 hospitals under the New Drug Introduction and Protection Program. Prolonged use decisions were made by a central expert committee based on individual treatment responses. Effectiveness was assessed through cumulative culture conversion rates and time; safety was evaluated by monitoring adverse events (AEs). Results:Of 481 patients, 421 received standard bedaquiline treatment, and 60 received prolonged treatment. Median culture conversion time was 4 weeks in both groups (P = 0.443), with one patient in the prolonged group achieving culture conversion after 24 weeks. Rates of QT prolongation (30.0% vs 28.5%), deaths (0% vs 2.1%), and other AEs were comparable. During the first 24 weeks, the prolonged group had a lower AE rate overall (35.0% vs 51.3%), including serious AEs (1.7% vs 13.8%), grade >3 AEs (13.3% vs 30.4%), AEs leading to death (0% vs 2.1%), bedaquiline-related AEs (16.7% vs 26.6%), and AEs leading to bedaquiline discontinuation (0% vs 5.7%). Conclusion:Prolonged bedaquiline use is effective and well-tolerated without significantly increased toxicity, potentially benefitting bedaquiline-tolerant patients with positive sputum cultures after the standard 6-month treatment.

To assess the implementation of infection prevention and control (IPC) measures in municipal and higher-level tuberculosis (TB)-designated medical institutions and to identify areas for improvement by comparing data from 2014 and 2022. This study compared infection control measures using data from 47 TB-designated medical institutions that participated in both the 2014 and 2022 national surveys. Implementation rates of administrative, environmental and respiratory protection measure were compared. A total of 47 institutions were analyzed, including 20 provincial institutions (42.6

BACKGROUND:China has the highest global disease burden for both lung cancer and tuberculosis (TB). Mobile low-dose computed tomography (LDCT) screening offers dual detection of early-stage lung malignancies and active TB radiographic manifestations. However, evidence regarding community-based post-screening compliance remains inadequate. This study aimed to evaluate hospital follow-up adherence and its associated factors among individuals who screened positive for lung cancer or TB in a community-based, non-risk-based LDCT screening program. METHODS:A prospective cohort study was conducted in Dongfang, Hainan Province, from June to September 2024. Permanent residents aged ≥40 years were enrolled in a community-based, non-risk-stratified mobile LDCT screening program. At the time of screening, participants completed a structured questionnaire to capture demographic characteristics, risk factors, and health status. Screening images were interpreted according to established guidelines; individuals with findings indicative of Lung-RADS category 4 (4 A, 4B, 4X) or suspected active pulmonary TB were considered screen-positive. The primary outcome, adherence to hospital-based diagnostic follow-up within six months, was objectively assessed by linking screening records to the provincial medical insurance claims database. Multivariable logistic regression was used to identify factors associated with adherence, stratified by screening finding. RESULTS:Among 22,933 participants (14,134 female and 8799 men), 547 (2.4%) had LDCT findings classified as Lung-RADS 4 and 653 (2.9%) displayed radiological features compatible with TB. Diagnostic follow-up within six months was completed by 303/547 lung-cancer suspects (55.4%) and 336/653 pulmonary TB suspects (51.5%). Among adherent individuals, 98 lung cancers (32.3%) and 95 active pulmonary TB cases (28.3%) were confirmed. In the lung-cancer cohort, respiratory symptoms increased the likelihood of follow-up (adjusted odds ratio [aOR] 2.47, 95% CI 1.13-5.41), whereas retired status decreased it (aOR 0.52, 0.32-0.85). In the pulmonary TB cohort, female sex was positively associated with adherence (aOR 1.39, 1.02-1.90), while formal employment was negatively associated (aOR 0.53, 0.31 - 0.90). CONCLUSIONS:This study highlights the need for targeted interventions to optimize diagnostic follow-up and maximize the clinical and public health impact of integrated lung cancer-TB screening programs.

BACKGROUND Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease endemic to tropical and subtropical regions that displays highly variable clinical presentations, ranging from localized abscesses to severe septicemia. Sequence type (ST) 271 has been rarely reported; data concerning its clinical and epidemiological characteristics remain limited. This report describes a rare case of ST271 infection presenting with rapidly progressive cavitary pneumonia and reversible hepatic injury. CASE REPORT A previously healthy 50-year-old male construction worker from Haikou, China, presented with a 2-week history of intermittent fever, hemoptysis, and persistent cough. Chest computed tomography revealed a thick-walled cavitary mass in the right upper lobe. Laboratory findings demonstrated substantially elevated liver enzymes, indicating acute hepatic injury. Metagenomic sequencing of bronchoalveolar lavage fluid identified B. pseudomallei, and whole-genome sequencing classified the isolate as ST271. The strain was sensitive to imipenem, ceftazidime, and trimethoprim-sulfamethoxazole; preliminary in vitro bacteriophage susceptibility also was observed. After initiation of intravenous ceftazidime followed by oral trimethoprim-sulfamethoxazole, the patient showed rapid clinical improvement that included robust resolution of the pulmonary lesion and normalization of liver enzymes, consistent with reversible hepatic injury. CONCLUSIONS This case highlights the aggressive clinical course of the rare B. pseudomallei ST271 strain, characterized by rapidly progressive cavitary pneumonia and concurrent hepatic injury in an immunocompetent host. Early identification using sequencing techniques facilitated timely targeted therapy and a favorable recovery. The observed in vitro phage susceptibility may provide preliminary insight for future research into alternative management strategies for resistant strains.

Abstract Background Delamanid (DLM) is a promising drug recommended for treatment of multidrug-/rifampicin-resistant tuberculosis (MDR/RR-TB). However, there are very little data about the emergence of drug resistance in patients with the use of DLM-containing regimens. The study aimed to monitor the dynamics of susceptibility of MTB to DLM and investigate the potential mechanism conferring decreased susceptibility. Methods A prospective cohort study was conducted, enrolling MDR/RR-TB patients with culture-confirmed diagnoses across 10 study sites. Serial sputum samples were collected from participants receiving DLM-containing regimens at baseline (treatment initiation), week 2, week 4, and every 4 weeks thereafter until treatment completion. The in vitro susceptibility of Mycobacterium tuberculosis isolates to DLM was assessed using the BACTEC MGIT 960 system. Results A total of 263 MDR/RR-TB patients were included from 2020 to 2024 in the present study, favorable outcomes were recorded in 187 patients (71.1%). The distribution of minimal inhibit concentration (MIC) for a bacterial population to DLM was unimodal, and most isolates tested had a MIC value of < 0.015 µg/mL. The MIC50 and MIC90 of MTB isolates were 0.03 and 0.06 µg/mL, respectively. Using the 0.12 µg/mL as a proposed epidemiological cutoff value, the resistance to DLM was found in 0.76% (2/263) of MTB isolates and no mutations were identified within loci conferring DLM resistance. Additionally, the remaining 81 (30.8%) with serial isolates were included in our analysis. 70 out of 81 patients exhibited no change in DLM MICs. In contrast, the reduced susceptibility to DLM was noted in 11 patients, defined as no less than 2-fold increase in MIC value compared with that of baseline. Conclusions Primary DLM resistance was rare (0.76%), and resistance emergence during treatment was infrequent, though some cases of reduced susceptibility were observed.

Background Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health burden. A growing body of evidence suggests that mucosal microbial communities may reflect or modulate host responses during infection. However, the oral microbiome in TB patients with different bacterial loads remains poorly characterized. This study aimed to investigate alterations in oral fungal communities among Xpert-positive patients, stratified by Mtb burden based on Xpert MTB/RIF testing.Methods In this prospective multicenter cohort study (May-August 2024), 278 Xpert-positive TB patients were enrolled across five hospitals in China. Participants were stratified into high, medium, low, and very low Mtb burden groups according to Xpert MTB/RIF cycle threshold values. Paired sputum and tongue swab samples were collected. Oral fungal profiles were characterized via ITS sequencing, followed by taxonomic assignment, diversity analysis, and multivariable association testing (MaAsLin 2) to identify robust biomarkers.Results Oral fungal community structure varied significantly across Mtb burden strata. Beta-diversity analysis revealed distinct clustering between the very low burden group and higher burden groups (high, medium, low). High-burden patients were enriched with environmental taxa such as Blumeria and Toxicocladosporium, whereas low-burden groups exhibited higher abundances of Candida, Aspergillus, and Penicillium. Notably, MaAsLin 2 analysis confirmed that Penicillium and Podosphaera were independently associated with lower Mtb burden after adjusting for confounders. Neutral model analysis indicated that stochastic processes predominantly drive the assembly of these oral fungal communities. Functional prediction suggested enhanced aerobic respiration and metabolic enzyme activity in high-burden groups.Conclusions This study analyzed the oral fungal microbiome stratified by Mtb burden strata in Xpert-positive patients, revealing distinct shifts in fungal composition and functional potential. Fungal dysbiosis and altered microbial metabolic capacity may offer insight into host-microbe interactions in pulmonary TB (PTB). These findings underscore the potential value of fungal microbiome profiling for assessing Mtb burden, beyond its application in TB diagnosis alone.

Background Early assessment of tuberculosis progression and the efficacy of anti-tuberculosis drugs is crucial for improving disease cure rates. This study aimed to predict the therapeutic efficacy of newly diagnosed sputum-negative but bronchial alveolar lavage fluid (BALF)-positive pulmonary tuberculosis patients after intensive therapy. Methods We collected data from 255 patients (178 and 77 in center 1 and 2, respectively) diagnosed with newly diagnosed sputum-negative but BALF-positive pulmonary tuberculosis. Based on imaging and clinical follow-up results, the patients were divided into progression and improvement groups. Radiomics features were extracted from five computed tomography (CT) signs, and feature selection was performed using Pearson correlation analysis and the Least Absolute Shrinkage and Selection Operator (LASSO). Three machine learning models (random forest (RF), support vector machine (SVM), and logistic regression (LR)) were then constructed. Predictive performance was evaluated using receiver operating characteristic (ROC) curves, F1 scores, and Delong tests. Results A total of 118 radiomics features were used to construct three models that demonstrated good performance. In the training and test cohorts, the SVM model achieved area under the curves (AUCs) of 0.917 and 0.858, and F1 scores of 0.808 and 0.755, respectively. The RF model showed the highest predictive performance with AUCs of 0.996 and 0.824, and F1 scores of 0.982 and 0.832. The LR model achieved AUCs of 0.927 and 0.808, and F1 scores of 0.867 and 0.747. Conclusions Machine learning models based on radiomic features extracted from various CT signs demonstrate potential for predicting the therapeutic efficacy in newly diagnosed pulmonary tuberculosis patients after intensive therapy, providing effective guidance for subsequent treatment.

The Swift Burst Alert Telescope (BAT), operating in the 15-150 keV band, cannot directly measure the peak energy (E-p) for most gamma-ray bursts (GRBs), as typical E-p values of 200-300 keV lie beyond its upper energy limit. In this paper, we develop a method to robustly estimate the lower limit of E-p for GRBs with E-p > 150 keV by exploiting the intrinsic spectral curvature already evident within the BAT energy range. Fitting BAT spectra with a cutoff power-law model and extrapolating the spectral curvature, we estimate the cutoff energy (E-c') beyond 150 keV and the corresponding peak energy (E-p'). Applying this method to 17 GRBs, we identify two main groups: Group I (10 bursts) exhibits typical photon indices (-1.20 less than or similar to alpha less than or similar to -0.8) with increasing E-c, while Group II (two bursts) shows typical E-c values (300-500 keV) with varying alpha. For E-c less than or similar to 1000 keV, the estimated E-c' agrees well with observed values. The reliability of E-c' depends on alpha: harder spectra (alpha greater than or similar to -2/3) show reduced accuracy, while softer spectra (alpha less than or similar to -2/3) yield more precise estimates. We validate this method using Swift/BAT data for nine GRBs with simultaneous Fermi Gamma-ray Burst Monitor detections, successfully recovering E-c' consistent with broadband measurements in 89% of cases. In conclusion, this method is therefore well suited for GRB spectra with moderately constrained E-c (E-p) values and photon indices that are not too hard.

Central carbon metabolism is fundamental to the growth and virulence of Mycobacterium tuberculosis (Mtb). The aceE gene encodes the E1 subunit of the pyruvate dehydrogenase complex that irreversibly converts pyruvate to acetyl-CoA. There, we investigated the impact of aceE inactivation on the physiological metabolism of Mtb. An aceE deletion in Mtb H37Rv was constructed, and the mutant was compared to wild type (WT) by in vitro growth assays, colony morphology, biofilm formation, stress tolerance, lipidomics, RNA-seq, and BALB/c mouse infection. Mtb ΔaceE exhibited markedly slower planktonic growth, smooth colony morphology, impaired biofilm formation, and was more sensitive to acid, NaNO2, and some commonly used antibiotics. Lipidomics revealed global depletion of mycolic acids and major phospholipids in Mtb ΔaceE mutant. Transcriptome analysis showed downregulation of TCA cycle and fatty-acid biosynthetic genes. Two weeks after intravenous infection, lung bacillary loads were 0.6 log10 lower for ΔaceE than in WT, and spleen enlargement was absent, yet the mutant persisted, and pathology was otherwise comparable to WT. AceE is required for robust lipid anabolism, biofilm formation, and maximal growth of Mtb in vitro, especially on carbohydrate-based media, but its absence only modestly attenuates acute virulence in mice, underscoring the pathogen's metabolic plasticity during infection.IMPORTANCEThe present study demonstrated that the aceE gene, a crucial enzyme that links glycolysis and the TCA cycle, plays a vital role in regulating the normal physiological metabolism of Mycobacterium tuberculosis (Mtb). The aceE gene not only aids in the bacteria's energy metabolism but also promotes lipid synthesis, forming a thicker cell wall that helps Mtb resist various intracellular stresses, further favoring its survival within the host cells. During in vivo survival, the increased expression of the aceE gene in the virulent Mtb H37Rv strain may enhance the conversion of pyruvate into acetyl-CoA, thereby providing more precursor materials for the synthesis of lipids and amino acids.

Tuberculosis (TB) remains the leading cause of mortality caused by a single infectious agent. Targeted next-generation sequencing (tNGS) has become a promising molecular method for TB diagnosis, but its accuracy and application for non-sputum specimens still remain unexplored. In this multicenter prospective lab-developed assay, 701 participants from five designated TB hospitals from different provinces in China were recruited. Non-sputum specimens were collected for tNGS, Xpert Mycobacterium tuberculosis (MTB)/RIF (Xpert), and culture tests. The diagnostic accuracy of tNGS for TB patients was evaluated compared with the microbiological reference standard (MRS). Phenotypic drug susceptibility tests (DSTs) were conducted using culture-positive isolates and employed to assess the accuracy of tNGS for detecting drug resistance. We found that the tNGS assay exhibited high diagnostic accuracy with sensitivity and specificity of 93.4% (95% CI, 91.5%-95.2%) and 93.2% (95% CI, 91.3%-95.0%) when utilizing MRS as the gold standard. The diagnostic performance of tNGS was robust regardless of specimen types and clinical symptoms. tNGS also showed a detection potential for other coinfecting respiratory pathogens. More than 90% of tNGS-positive individuals gained drug susceptibility results, which were mainly dependent on bacterial loads. Compared with phenotypical DSTs, tNGS had high sensitivities and specificities for the detection of rifampicin, isoniazid, streptomycin, ethambutol, and levofloxacin resistance. Our findings illustrated that tNGS assay is a rapid and highly sensitive test for TB diagnosis and simultaneous detection of drug resistance in non-sputum specimens. Its accuracy gain compared with conventional methods is most remarkable in TB patients with low bacterial loads.IMPORTANCETuberculosis (TB) diagnosis still remains challenging, especially in non-sputum patients. Nanopore-based targeted next-generation sequencing (tNGS) is a promising technology for the detection of TB cases and drug resistance, which has capacities to provide a panel of drug resistance profiles. The purpose of this study is to explore the diagnostic performance of tNGS for non-sputum specimens from five designated TB hospitals from different regions in China. Compared with the microbiological reference standard (MRS), tNGS exhibited high sensitivity and specificity, which are associated with bacterial loads in samples. Meanwhile, tNGS has capacities to detect coinfecting respiratory pathogens and produce drug-resistant profiles. Therefore, our findings suggested that tNGS is an alternative method for the diagnosis of non-sputum TB patients.CLINICAL TRIALSThis study is registered with Chinese Clinical Trial Registry as ChiCTR2400088518.