Drug-susceptible pulmonary tuberculosis (DS-PTB) is conventionally treated with a 6-month multidrug regimen, but prolonged treatment may compromise adherence, prompting efforts to develop shorter and effective therapeutic strategies. However, the comparative long-term effectiveness of alternative regimens, particularly their ability to prevent relapse, remains uncertain. We systematically searched multiple databases from inception through August 31, 2025, for randomized controlled trials enrolling adolescents and adults with DS-PTB. Regimens were classified according to treatment duration and architecture, including standard 6-month therapy, rifamycin-intensified strategies, structurally modified 6-month regimens, 4-month treatment-shortening approaches, and intended 8-week multidrug regimens. A random-effects pairwise meta-analysis and a fixed-effect consistency network meta-analysis (NMA) compared treatment success, relapse/recurrence-related outcomes, and mortality. Eight randomized controlled trials involving 10,244 participants were included. Six source trials involving 8,457 randomized participants contributed to the quantitative synthesis and informed a 14-node NMA; outcome data from 6,752 participants contributed to 12 shortened-regimen-versus-standard comparisons in the pairwise meta-analysis. Two trials involving 1,787 participants were summarized narratively because their thrice-weekly control regimens were not considered exchangeable with the daily reference regimen. In the pooled pairwise analysis, shortened-duration regimens were associated with a higher risk of trial-defined unfavorable long-term outcomes than the 6-month standard regimen (RR = 1.68, 95% CI 1.37-2.06; P < 0.001; I² = 39.9%). Treatment success was close to that of the standard regimen for the 4-month daily rifapentine-moxifloxacin regimen evaluated in Study 31/A5349 (RR = 0.98, 95% CI 0.94-1.01) and the 6-month regimen with once-weekly rifapentine-moxifloxacin continuation therapy evaluated in RIFAQUIN (RR = 1.01, 95% CI 0.93-1.09). In contrast, all four intended 8-week TRUNCATE-TB regimens showed lower treatment success and higher relapse/recurrence-related risk estimates than the standard regimen. Mortality was uncommon, and mortality comparisons were imprecise. These findings suggest that long-term outcomes should be interpreted in relation to regimen design, dosing, and treatment duration rather than duration alone. The standard 6-month regimen remains a reliable reference, and conclusions about individual alternatives should be based on effect estimates and uncertainty rather than rankings. Because no closed loop was formed by independent trial evidence, formal inconsistency assessment was not feasible.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251267175.

Biologic therapies targeting the interleukin-5 (IL-5) pathway improve asthma control and chronic rhinosinusitis with nasal polyposis (CRSwNP) in patients with non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD). However, their effect on NSAID tolerance remains insufficiently characterized.

This study aimed to investigate whether anti-IL-5/IL-5 receptor (IL-5R) treatments could improve NSAID tolerance in patients with NERD and Blended Reactions (BRs).

Clinical parameters, including the Asthma Control Test (ACT), 22-item Sino-Nasal Outcome Test (SNOT-22), visual analog scale (VAS) scores for quality of life, nasal polyp grade, and inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) dose, were compared before and after biologic therapy. ASA provocation tests were repeated during biologic treatment and compared with prior challenge results; outcomes were also compared between the biologic-treated group and the biologic-naive comparison group.

Patients who received biological treatments showed significant improvements compared to baseline, with eosinophil counts decreasing from 695 (590-892.5) to 50 (30-60), ACT scores increasing from 12 (8.7-18) to 24 (20.7-24.2), SNOT-22 scores declining from 56 (51-73) to 16 (5.7-28.7), and VAS scores improving from 1 (0-2.2) to 9 (7-10), all with p=0.001. ASA provocation positivity decreased to 28.5% (p=0.002), and all patients stepped down from high-dose to medium/low-dose ICS/LABA. Among the four patients who remained intolerant, reactions occurred at higher cumulative doses, with delayed onset and milder symptoms.

Our study indicated that blockade of IL-5 pathway significantly improved clinical outcomes and reduced ASA hypersensitivity in patients with NERD/BRs, highlighting their potential role in modifying disease phenotype beyond asthma control.

Neonatal sepsis remains a leading cause of mortality and long-term disability worldwide. The coronavirus disease 2019 (COVID-19) prevention measures effectively curbed viral transmission. However, evidence of their long-term impact on the pathogen spectrum and antimicrobial resistance in neonatal sepsis is limited.

In this single-center retrospective observational study at Henan Children's Hospital, 894 neonates with culture-confirmed sepsis (2015-2024) were enrolled. Using pandemic policy time points, we divided the study into three phases and compared pathogen spectrum and antimicrobial resistance.

Among neonates with sepsis, preterm proportion increased from 32.5% to 46.2%. The pathogen spectrum shifted from Gram-positive to Gram-negative predominance. Coagulase-negative staphylococci (CoNS) detection declined from 36.6% to 9.8%, a trend consistent across preterm/full-term and early-onset/late-onset subgroups. Klebsiella pneumoniae (K. pneumoniae) maintained high resistance to third-generation cephalosporins, while Escherichia coli (E. coli) showed a numerical increase in ceftazidime resistance. In contrast, CoNS and Enterococcus faecium (E. faecium) remained susceptible to vancomycin and linezolid. E. coli maintained favorable susceptibility to carbapenems and piperacillin-tazobactam, whereas K. pneumoniae showed a fluctuating carbapenem resistance trend that initially increased then declined, though it remained susceptible to tigecycline. All-cause mortality increased from 1.4% to 5.4%, with Gram-negative bacteria predominating in fatal cases.

Enhanced hand hygiene and contact isolation are consistent with a sustained decline in CoNS, but show limited association with changes in Gram-negative bacilli. Routine surveillance and optimized empirical therapy remain crucial for improving neonatal sepsis outcomes.

to assess national trends in the use of emergency contraception (EC) and rates of induced abortion in Italy from 2017 to 2023, considering the impact of the COVID-19 pandemic and the 2020 AIFA decision that expanded over-the-counter access to ulipristal acetate (UPA) for minors.  Design: quasi-experimental ecological study using Interrupted Time Series (ITS) analysis of national data on EC use and induced abortion rates. Three interventions were evaluated: onset of the COVID-19 pandemic, end of the first lockdown, and the AIFA policy for minors. Hormonal contraceptive use and total fertility rates were included as control series.

monthly aggregated data from 2017 to 2023 on EC use, hormonal contraception, induced abortions, and fertility rates among the Italian resident women aged 15-49 years.

use of EC and UPA, induced abortion rates, regular hormonal contraceptive use, and total fertility rates. ITS parameters were expressed as incidence rate ratios (IRRs) with 95% confidence intervals.

between 2017 and 2023, EC use increased from approximately 3 to 5 packages dispensed per 1,000 women, with UPA use increasing approximately twofold. The COVID-19 pandemic was associated with a temporary but significant decline in EC use and induced abortions, followed by a rapid post-lockdown rebound (IRR trend UPA: 2.22; 95%CI 1.57-3.15; IRR trend induced abortion: 1.20; 95%CI 1.01-1.42). Induced abortion rates declined modestly but steadily (IVG: from 0.59 in January 2017 to 0.44 in December 2023), while fertility rates (from 3.06 in January 2017 to 3.07 in December 2022) and hormonal contraceptive (from 155.82 in January 2017 to 176.82 in December 2023) use remained stable. No ecological evidence of substitution effect following increased EC access was observed.

extending over-the-counter access to UPA for minors was associated with increased use without reducing hormonal contraceptive use. Changes observed during the COVID-19 pandemic were temporary and followed by a rapid recovery, without altering long-term trends. The modest decline in induced abortion rates is consistent with a pre-existing trend rather than a direct effect of expanded EC availability, suggesting a complementary role of EC within broader reproductive health strategies.

Patients with post-acute sequelae of SARS-CoV-2 (PASC) fear SARS-CoV-2 vaccine-linked symptom aggravation. Data on objective functional outcomes are limited.

We performed a retrospective analysis of an observational cohort at a post-COVID outpatient clinic at Hannover Medical School with standardized assessments at baseline and follow-up visit (3-6 months) in adults with confirmed SARS-CoV-2 infection and PASC. Participants were classified as vaccination (receipt of an additional SARS-CoV-2 vaccine dose between visits) or no vaccination. Primary outcomes were fatigue (Fatigue Assessment Scale) and exercise capacity (6-minute walk distance). Propensity scores matching (1:1 nearest-neighbor, ATT; caliper 0.2 SD) was performed using logistic regression. Group differences were assessed using t-tests/χ² tests with Benjamini-Hochberg adjustment. Longitudinal changes were analyzed using linear mixed-effects models.

Of 193 eligible patients, 174 were analyzed, 148 remained after matching (74 per group). No significant differences between the groups were observed at baseline or follow-up after adjustment for multiple comparisons. Both groups improved over time, with no statistically significant difference in fatigue or exercise capacity.

Fatigue and functional performance improved over time regardless of vaccination status. We found no statistically significant association between mRNA SARS-CoV-2 vaccination and worsening symptoms or impaired recovery, although smaller effects cannot be excluded.

The popularity of Generative Artificial Intelligence (AI)-powered chatbots is growing, with more patients using AI to understand respiratory conditions, including bronchiectasis. The quality of AI's responses to bronchiectasis-related questions has not previously been evaluated.

To evaluate the reliability, accuracy, comprehensiveness, and understandability of responses generated by different AI-based chatbots to bronchiectasis-related questions formulated by patients.

Cross-sectional international study.

People living with bronchiectasis from the EMBARC/European Lung Foundation (ELF) patient advisory group formulated 15 bronchiectasis-related questions, categorised into 3 difficulty tiers. These questions were submitted to three AI-based chatbots: ChatGPT, Bard, and Copilot. An international group of 28 experts from the European Respiratory Societies (recruited through Assemblies and the CONNECT clinical research collaboration) and 33 patients evaluated the answers' reliability, accuracy, comprehensiveness, and understandability.

Of 45 outcomes, 37 were deemed reliable. Median accuracy scores ranged from 6.0 to 9.0, with ChatGPT scoring higher than Copilot and Bard (8.0 [7.0-9.0] vs 7.0 [6.0-8.0] vs 7.0 [6.0-8.0], p-value < 0.001). Median comprehensiveness scores ranged from 6.0 to 9.0, with ChatGPT providing more comprehensive answers compared to Bard and Copilot (8.0 [7.0-9.0] vs 8.0 [6.0-9.0] vs 7.0 [6.0-8.0], p-value < 0.001). Median understandability scores ranged from 7.0 to 10.0, with ChatGPT and Bard delivering more understandable answers than Copilot (9.0 [8.0-10.0] vs 9.0 [8.0-10.0] vs 9.0 [7.0-10.0], p-value < 0.001). Differences in understandability were noted in Bard's responses across difficulty tiers (easy 9.0 [8.0-10.0] vs medium 9.0 [7.0-10.0] vs difficult 8.0 [7.0-10.0], p-value = 0.012).

AI software, particularly ChatGPT, provided accurate, comprehensive, and understandable answers to our 15 bronchiectasis-related questions.

To investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic and its subsequent normalized prevention and control phase on the body mass index (BMI) and prevalence of overweight and obesity among adolescents aged 13-18 years in China, providing a basis for formulating growth and development intervention strategies in the post-pandemic era.

Using a random cluster sampling method, 120,459 adolescents aged 13-18 years from 15 junior and senior high schools across 4 districts/prefectures in Xinjiang, China, were selected as study subjects based on geographical distribution characteristics from 2017 to 2021. Height and weight were measured in strict accordance with the National Student Physical Health Standard, and physical status was classified into underweight, normal weight, overweight, obesity, and combined "overweight+obesity" based on BMI. Relevant data were analyzed using normality tests, one-way ANOVA, χ² test, and binary logistic regression, accounting for the clustered sampling design. The significance level was set as 5%.

The mean BMI of adolescents aged 13-18 years in 2020 increased significantly by 0.2 kg/m² compared with previous years, while showing a declining trend in 2021 (F=104.862, P<0.001). BMI changes exhibited gender and age differences, with girls showing greater fluctuation than boys (F = 114.950, 30.063, both P < 0.001). Statistically significant differences were also observed across all age groups (all P < 0.05). Detection rates of nutritional status categories showed: compared with 2017-2019, the underweight rate decreased to 10.6% in 2020, while overweight and "overweight+obesity" rates increased to 9.5% and 12.0%, respectively (both P<0.05); compared with 2020, the underweight rate rebounded to 13.9% in 2021, while overweight and "overweight+obesity" rates decreased to 8.0% and 10.7%, respectively (both P<0.05), with particularly significant changes observed in girls and the 13-15-year-old group. Logistic regression analysis (with 2017 as reference) indicated that in 2020, the risk of underweight decreased (OR=0.668, 95% CI: 0.633-0.706), while the risks of overweight (OR=1.280, 95% CI: 1.199-1.366) and "overweight+obesity" (OR=1.364, 95% CI: 1.286-1.448) increased; in 2021, the risk of underweight increased (OR=0.917, 95% CI: 0.872-0.965), while the risk of "overweight+obesity" decreased (OR=1.201, 95% CI: 1.131-1.275), with these associations being more pronounced in girls.

The initial stage of the COVID-19 pandemic was associated with a significant negative impact on the weight status of Chinese adolescents aged 13-18 years, manifested by increased BMI and elevated detection rates of overweight and obesity. As prevention and control entered a normalized phase, this impact gradually diminished, with weight distribution showing a tendency to return to pre-pandemic status. Future efforts should focus on strengthening long-term dynamic monitoring of adolescent weight changes and developing and implementing precise health interventions to prevent undesirable physical status and promote the overall healthy development of adolescents.

The SARS-CoV-2 main protease (M^pro) is a promising target for coronavirus disease 2019 (COVID-19) therapy due to its high conservation and essential role in viral replication. In this study, 148 crystal structures of SARS-CoV-2 M^pro complexed with non-covalent inhibitors from the Protein Data Bank (PDB) were used to map the inhibitor binding site using protein-ligand interaction fingerprints (IFPs). The analysis revealed that the S2 binding site serves as a key region to anchor most non-covalent inhibitors. This mapping was used as a guide to virtually screen an in-house Thai natural product database for potential inhibitors of SARS-CoV-2 M^pro. Seven hit compounds were selected based on docking results, including pose quality, interaction profiles, and energetic criteria. Molecular dynamics simulations confirmed the stability of the SARS-CoV-2 M^pro-hit compound complexes, revealing that panduratin A (CPD3), deacetylmammea E/BA cyclo D (CPD4), and n-pentyl beta-carboline-1-propionate (CPD5) were particularly interesting virtual hits, as they consistently formed strong interactions with key residues at the S2 site through π-π, H-π, and hydrogen bonds.

Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections in infants, older adults, and immunocompromised individuals, but therapeutic options for active infection remain limited. Interleukin-6 (IL-6) contributes to RSV replication and RSV-induced inflammation, and the IKKβ/NF-κB pathway is a major regulator of IL-6 expression. Bardoxolone methyl (BXM) was identified by network medicine as a potential anti-RSV compound, with molecular docking suggesting interactions with the IKKβ/NF-κB pathway. We investigated whether BXM inhibits RSV infection through modulation of the IKKβ/NF-κB/IL-6 axis in RSV-infected BEAS-2B cells and BALB/c mice. RSV infection increased IL-6 expression and activated IKKβ/NF-κB signaling, whereas IL-6 knockdown reduced viral replication and inflammatory mediator expression. BXM significantly suppressed RSV replication, as shown by RT-qPCR, TCID₅₀, plaque reduction assays, and Western blotting, and decreased IL-6 expression in vitro. Mechanistically, BXM attenuated RSV-induced phosphorylation of IKKβ and NF-κB. The IKKβ inhibitor TPCA-1 produced similar inhibitory effects, whereas recombinant human IL-6 add-back partially restored inflammatory mediator expression in BXM-treated RSV-infected cells. In mice, BXM reduced lung viral titers, RSV-F expression, IL-6 expression, IKKβ/NF-κB activation, and RSV-induced lung injury. These findings suggest that BXM suppresses RSV replication and inflammation, at least in part, by modulating the IKKβ/NF-κB/IL-6 axis, supporting its potential as a therapeutic candidate for RSV infection.IMPORTANCERespiratory syncytial virus (RSV) is a major cause of respiratory illness, especially in infants, older adults, and people with weakened immune systems. Although preventive strategies are available for some high-risk groups, treatment options for active RSV infection remain limited. This study identifies bardoxolone methyl (BXM) as a potential anti-RSV compound and shows that it can reduce both viral replication and virus-induced inflammation in cell and mouse models. Importantly, our findings suggest that BXM acts, at least in part, by reducing IL-6-related inflammatory signaling, which is closely associated with RSV disease severity. These results provide experimental evidence supporting BXM as a promising candidate for further development against RSV infection and offer insight into a potential host-targeted therapeutic strategy.

La frecuencia de la tos ferina fue controlada en varios países con la vacunación, aunque ha reemergido en las últimas décadas. Poco se sabe de la historia de esta enfermedad en Colombia; este trabajo resume la historia de la tos ferina en el país desde un enfoque poblacional. Las evidencias sugieren que la tos ferina apareció hacia finales del siglo XV en Persia, y desde esa época ha sido endémica, especialmente entre los menores de edad. Al territorio colombiano debió llegar durante el siglo XVIII o a inicios del XIX. En Colombia, se han presentado importantes epidemias, en especial antes de que existiera la vacuna contra Bordetella pertussis. Las epidemias más importantes tuvieron lugar en Bogotá (1814) y en Cajicá (1922). La vacunación fue muy efectiva en la segunda mitad del siglo XX, aunque hubo brotes entre las poblaciones no vacunadas de las zonas rurales y entre los indígenas de diversos lugares del país. Actualmente, la tos ferina es una amenaza para Colombia por los casos traídos del exterior o en personas sin vacunar.