Yellow fever is a long-standing zoonotic arboviral disease that affects hundreds of thousands of people annually in different regions of the world, even though the vaccine has been available since the 1930s. Thus, studies that synthesize general and current information on yellow fever are relevant, aiming to disseminate knowledge that can contribute to mitigating its impacts. This narrative review synthesizes the general aspects of yellow fever, discusses its impacts on public health, and presents information on the use of the One Health approach in the context of this zoonosis. The databases used to select the articles were PubMed, Scopus, LILACS, and SciELO, using various descriptors related to the study's theme and objectives. It is important to highlight that yellow fever remains a significant public health challenge due to its high mortality rate in severe cases and the continued circulation of the yellow fever virus in tropical areas, especially in South America and Africa. Although many patients recover spontaneously, recurrent outbreaks continue in endemic regions. The initial clinical similarity to other zoonoses makes timely diagnosis difficult, and management remains restricted to clinical support, as there is no specific antiviral treatment. Vaccination and epidemiological surveillance stand out as the main preventive measures. Additionally, considering that the management of yellow fever involves human, animal, and environmental health aspects, the One Health approach stands out as a modern, robust, and effective alternative for addressing this zoonosis. However, the lack of knowledge regarding this approach among public managers and health professionals results in its non-use and, consequently, impacts the fight against yellow fever. Therefore, it is important to widely disseminate knowledge about the One Health approach, aiming at carrying out holistic actions in the human-animal-environmental interface sectors in the context of yellow fever, allowing for coordinated and sustainable responses at different levels and instances.
Bundibugyo ebolavirus (BDBV) is one of the least studied species within the genus Orthoebolavirus (family Filoviridae), despite its capacity to cause severe Ebola virus disease (EVD) with substantial mortality. First identified during a 2007-2008 outbreak in Bundibugyo District, western Uganda (149 reported cases, 37 deaths; case-fatality rate [CFR] approximately 25-36%), BDBV re-emerged in 2012 in Orientale Province, Democratic Republic of the Congo (DRC) (57-59 cases, 29-34 deaths; CFR 34-58%), before resurfacing in Ituri Province, DRC, in April-May 2026. By 11 August 2026, this third outbreak had grown to 4566 laboratory-confirmed cases and 2128 deaths (CFR ≈ 47%) across five DRC provinces and Uganda, becoming the largest, fastest-growing BDBV epidemic on record and the second-largest Ebola-family outbreak overall. This narrative review, not a systematic review or meta-analysis, summarizes peer-reviewed literature, preprints, and official situation reports from WHO, Africa CDC, US CDC, ECDC, and national health ministries, identified through PubMed, Scopus, Web of Science, Google Scholar, and Embase from inception to 12 August 2026, to examine BDBV historical evolution, virology and pathogenesis, drivers of re-emergence, surveillance and response, therapeutic and vaccine gaps, and global health security implications. The 2026 outbreak, unfolding amid conflict and mass displacement in eastern DRC, has been marked by an estimated basic reproduction number of 1.4-2.1 (central estimate 1.71), disproportionate infection among healthcare workers (7.2% of confirmed cases in DRC, 20% in Uganda), and the continued absence of licensed BDBV-specific vaccines or therapeutics. Findings underscore the need for sustained genomic and ecological surveillance, decentralized rapid diagnostics, broadly protective pan-filovirus vaccines, conflict-sensitive response strategies, and strengthened Uganda-DRC collaboration. Because the evidence base for the ongoing outbreak remains preliminary, findings should be interpreted cautiously and revisited as further peer-reviewed data emerge.
Objective:To retrieve, appraise, and synthesize the best available evidence on the prevention of ventilator-associated pneumonia (VAP) from Chinese and international sources, and to provide evidence-based guidance for clinical nursing practice. Methods:Guided by the 6S evidence pyramid model, a comprehensive electronic search was conducted in BMJ Best Practice, UpToDate, the Guidelines International Network, the National Institute for Health and Care Excellence, the Scottish Intercollegiate Guidelines Network, the Registered Nurses' Association of Ontario, the American Association for Respiratory Care, the American Thoracic Society, CHEST, the Cochrane Library, the IBI Evidence-Based Health Care Center database, Embase, PubMed, Medlive, the Chinese Thoracic Society, the Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang Database. The search period ranged from January 1, 2016, to January 1, 2026. Evidence summaries, clinical practice guidelines, systematic reviews, and other evidence-based resources related to VAP prevention were retrieved. After quality appraisal and evidence synthesis, the best evidence was summarized. Results:A total of 24 publications were included, comprising 2 clinical decision support resources, 10 systematic reviews, 5 guidelines, and 7 evidence summaries. Thirty-three recommendations were synthesized into eight practical domains covering organizational strategies, prevention bundles, airway management, positioning, nutrition, device management, pharmacologic approaches, and non-recommended interventions. Conclusion:This evidence summary systematically synthesizes the best available evidence regarding VAP prevention and provides evidence-based guidance for standardized clinical management. These findings may support clinical decision-making and the development of nursing practice strategies for VAP prevention; however, further studies are needed to evaluate the effectiveness of implementing these recommendations in specific clinical settings.
Jinyang Li,1 Hongmin Yuan,2 Yanli Niu21Orthopedics Department, Huaihe Hospital of Henan University, Kaifeng, Henan, People’s Republic of China; 2School of Basic Medical Sciences, Henan University, Kaifeng, Henan, People’s Republic of ChinaCorrespondence: Yanli Niu, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, People’s Republic of China, Email nyl0925@henu.edu.cnBackground: Postoperative infection is a serious complication in older adults undergoing surgery for intertrochanteric femoral fracture (IFF). This study aimed to develop a simple scoring system and nomogram for predicting postoperative infection using routinely available preoperative indicators.Methods: A retrospective analysis was conducted on 286 older adult IFF patients (25 with postoperative infection, 261 without) treated at a single tertiary hospital. Optimal cut-off values were determined using the Youden index. Univariate and multivariate logistic regression identified independent risk factors. A nomogram and a simple scoring system (0– 3 points) were constructed. Model performance was assessed by AUC, calibration curve, and subgroup analyses. Bootstrap resampling (500 iterations) was used for internal validation.Results: Multivariate analysis confirmed the CRP/albumin ratio (OR = 2582.84, 95% CI: 201.44– 67,929.9, p < 0.001), fasting glucose (OR = 2.82, 95% CI: 1.32– 6.73, p = 0.011), and surgery duration (OR = 1.06, 95% CI: 1.01– 1.12, p = 0.020) as independent predictors. Optimal cut-offs were 1.85 (CRP/albumin), 7.6 mmol/L (glucose), and 89 minutes (surgery). The scoring system showed infection rates of 0%, 5.6%, 40.9%, and 100% for scores 0, 1, 2, and 3, respectively, with an AUC of 0.932. The full model achieved an AUC of 0.951, with Bootstrap-corrected AUC of 0.945 (95% CI: 0.923– 0.951). Calibration was satisfactory (Hosmer-Lemeshow, p = 0.327). Subgroup analyses demonstrated robust performance across gender, BMI, and age groups, with AUCs ranging from 0.922 to 0.982.Conclusion: In this single-center retrospective cohort, the CRP/albumin ratio, fasting glucose, and surgery duration were independent predictors of postoperative infection in older adults with IFF. The proposed simple scoring system and nomogram provide practical tools for risk stratification; however, external validation in multicenter prospective cohorts is warranted before widespread clinical implementation.Keywords: intertrochanteric femoral fracture, older adults, postoperative infection, CRP/Alb ratio, fasting glucose, surgery duration, scoring system, nomogram
Tianfang Chen,1,2,* Yelu Yao,2,* Jianwu Chen,3,* Huoyang Lv,1,2 Peng Nan21The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Department of General Surgery, Wencheng Hospital Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huoyang Lv; Peng Nan, Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email lab_lhx@126.com; nanpeng@hmc.edu.cnAbstract: This narrative review explores triazole resistance and pathogenesis of Aspergillus fumigatus (A. fumigatus) under a unified One Health framework, integrating evidence across host immune spectrums, agricultural environmental selection pressures, veterinary aspergillosis and clinical antifungal management. We illustrate layered host-fungus immune interactions underlying distinct clinical aspergillosis phenotypes, and delineate core resistance mechanisms including cyp51-related target alterations, enhanced efflux pump activity, biofilm-mediated tolerance and adaptive stress response rewiring. Special emphasis is placed on cross-sector transmission pathways of azole-resistant A. fumigatus (ARAF) originating from agricultural ecosystems, as well as surveillance deficits and public health risks linked to animal intermediate hosts. Novel antifungal agents, such as olorofim, fosmanogepix, rezafungin, ibrexafungerp, and T-2307, along with targeted delivery and immunomodulatory adjunct therapies for resistant aspergillosis, are also summarized. Literature published 2020– 2026 was retrieved from PubMed via Boolean search strategies, with supplementary manual screening of landmark reference lists to include pivotal earlier studies. Only peer-reviewed original studies, epidemiological surveillance reports, and review articles with complete clinical or experimental datasets were incorporated following rigorous screening. Most studies discuss clinical or agricultural resistance separately, lacking integrated analyses covering human, animal, and environmental dimensions. Major knowledge gaps persist regarding horizontal gene transfer of resistance mutations, cross-species transmission chains, and translational applications of environmental monitoring data. This review summarizes existing research bottlenecks and proposes integrated multi-sector prevention and control strategies from a One Health perspective to curb the growing threat of triazole-resistant aspergillosis.Keywords: Aspergillus fumigatus, Triazole resistance, pathogenesis, host immune spectrum, one health
Jianmei Chen,1 Liping Liu,1 Yanhua Zhang,2 Dong Ling,1 Feng Wang11Department of Clinical Laboratory, Chongzhou People’s Hospital, Chengdu, Sichuan Province, 611230, People’s Republic of China; 2Department of Healthcare-associated Infection Management, Chongzhou People’s Hospital, Chengdu, Sichuan Province, 611230, People’s Republic of ChinaCorrespondence: Jianmei Chen, Email 541719203@qq.comBackground: This study aimed to elucidate the molecular epidemiology and virulence characteristics of ST11 carbapenem-resistant Klebsiella pneumoniae (CRKP) colonizing the intestinal tract of elderly inpatients in the Chongzhou region, providing a basis for controlling the transmission of such resistant bacteria in high-risk populations.Methods: CRKP strains isolated from the intestines of elderly inpatients in this region between January 2023 and June 2024 were collected. ST11 strains were identified via multilocus sequence typing (MLST). Whole-genome sequencing, antimicrobial susceptibility testing, and string test, serum killing, biofilm formation, capsular polysaccharide quantification were employed to characterize their resistance genes, virulence genes, and molecular typing profiles.Results: Among 58 CRKP isolates, 17 (29.3%) were ST11. ST11-KL64 was the dominant clone (70.6%). All isolates carried the carbapenemase gene blaKPC-2 and exhibited extensive drug resistance, with tigecycline retaining the highest susceptibility (64.7%). The yersiniabactin system genes (ybtS, fyuA, entB) were universally present, whereas the aerobactin gene cluster (iucABCD-iutA) was detected in only 17.6% of isolates. The virulence regulator rmpA2 was incomplete in all carriers. The hypermucoviscosity phenotype was observed in 35.3% of isolates, which correlated with serum resistance in some strains. Biofilm formation was variable. The mortality rate among colonized patients was 35.3%.Conclusion: The ST11-KL64 clone is dominant among CRKP strains colonizing the intestinal tract of elderly patients in this region. This clone universally carries the blaKPC-2 gene conferring carbapenem resistance and exhibits a unique virulence gene profile characterized by a low carriage rate of classical hypervirulence markers and an incomplete rmpA2 regulator gene. This finding clarifies the local epidemic status of this clone and underscores the importance of implementing active surveillance and targeted prevention strategies for high-risk populations.Keywords: elderly patients, intestinal colonization, carbapenem-resistant Klebsiella pneumoniae, ST11, KL64 serotype, drug resistance genes, virulence genes
Haoan Sun,1 Jiangrong Luo21School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 2Department of Anesthesiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Jiangrong Luo, Department of Anesthesiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 1st Ring Road, Chengdu, Sichuan, 610072, People’s Republic of China, Tel +86-17744339763, Email 574085354@qq.comObjective: This study aims to investigate the pathogen spectrum and antimicrobial resistance trends in hospitalized infants in the neonatal intensive care unit (NICU) of our hospital (a major hospital in China) from 2019 to 2024. The evolving pathogen spectrum highlights the need for precise local diagnostic strategies based on surveillance data. The high prevalence of antimicrobial resistance calls for the optimization of empirical antimicrobial therapy and stringent antimicrobial stewardship. Additionally, this study provides evidence-based recommendations for cost-effective antimicrobial resistance control in resource-limited regions globally.Methods: A retrospective analysis of neonatal infection clinical data from the past five years was performed, focusing on the distribution of major pathogens and the evolution of antimicrobial resistance across the years.Results: A total of 566 distinct pathogens were isolated from 523 neonatal bacterial infection cases. Gram-positive bacteria represented the largest proportion (56.5%), with Staphylococcus aureus being the most common (173 strains, 30.6%). It demonstrated the highest resistance to penicillin (86.1%) and a relatively high resistance to erythromycin (52.6%), while remaining 100% sensitive to vancomycin, linezolid, and tigecycline. Staphylococcus epidermidis exhibited significant resistance to benzathine penicillin (75.3%) and erythromycin (62.3%), with a positive rate of 77.9% in the cefotaxime screening test. The proportion of Gram-negative bacteria was 43.5%. Among the Gram-negative pathogens, Escherichia coli showed high resistance (80.0– 86.1%) to cefoperazone-sulbactam and other β-lactams but only 0.9% resistance to carbapenems and full sensitivity to amikacin. Klebsiella pneumoniae exhibited significant resistance, with 34.1% of strains resistant to carbapenems.Conclusion: Over the past five years, Gram-positive bacteria have remained the predominant pathogens in NICU infections, with detection rates increasing annually. In contrast, the detection rate of Gram-negative bacteria has decreased. Gram-positive bacteria show high resistance to penicillin, while Gram-negative bacteria exhibit high resistance to third-generation cephalosporins. Additionally, multidrug-resistant strains have been identified. Temporal trend analysis revealed significant increasing trends for S. aureus (P=0.027) and S. epidermidis (P=0.038), and significant decreasing trends for E. coli (P=0.016).Keywords: newborn, bacterial infection, pathogen, drug resistance, neonatal intensive care unit
Morganella morganii (M. morganii), a member of the Enterobacteriaceae family, and a constituent of the human gut microbiota, has recently emerged as a candidate microbial contributor to the development of adenomatous polyps (AP) and promoting colorectal carcinogenesis. The present study is a narrative review compiled to evaluate the role of M. morganii in the development and progression of AP and colorectal cancer (CRC). A comprehensive literature search was conducted using Google Scholar and PubMed/Medline (2020-2026) using keywords related to the gut microbiota, M. morganii, and its impact on CRC and intestinal polyps. The ability of M. morganii to produce a specific type of genotoxin, indolimine, is a distinguishing feature of this bacterium compared to other intestinal bacteria. Because its production is independent of the pks gene cluster and the clbI and clbP genes, it exhibits a different damage pattern, namely, DNA smearing. According to reports from previous studies, strains lacking the aat gene exhibited no detectable genotoxic activity, supporting the role of aat in genotoxicity. Available data from in vitro experiments, animal models, a limited number of human observational studies, and findings from research groups suggest that M. morganii may, through the production of a highly potent genotoxin, be associated with distinct genetic damage, metabolic changes, and facilitation of polyp growth, and contribute to the development and acceleration of CRC. These findings establish a new theoretical framework in which CRC is not simply caused by gut microbiota dysbiosis, but rather reflects the activation of genotoxic bacteria and their functional interaction within the intestinal epithelial microenvironment. Nevertheless, owing to the scarcity of longitudinal human studies, it cannot yet be conclusively established whether M. morganii plays a predisposing, an initiating, or merely a consequential role in the development of CRC. Larger human studies investigating the association between M. morganii colonization and CRC development are essential for understanding the causal relationship.
Background:Sepsis is characterized by complex immune dysregulation involving innate immune activation, myeloid stress, and adaptive immune exhaustion. Conventional severity scores mainly reflect organ dysfunction and may not fully capture immune heterogeneity. This study aimed to develop and internally validate an immune-based model for predicting 28-day mortality in sepsis. Methods:This prospective cohort study included 695 participants, including 263 patients with sepsis, 160 infection non-sepsis patients, 152 non-infection critically ill patients, and 120 healthy controls. Immune biomarkers, including neutrophil CD64, heparin-binding protein (HBP), membrane-bound neutrophil alkaline phosphatase (mNAP), and PD-1⁺CD4⁺ T cells, were measured within 6 hours of ICU admission. A mortality prediction model was developed exclusively in the sepsis cohort using LASSO logistic regression and multivariable logistic regression. The model was internally validated using bootstrap resampling, Model performance was assessed using discrimination, calibration, decision curve analysis, and bootstrap internal validation. Results:Sepsis patients exhibited significantly higher levels of CD64, HBP, mNAP, and PD-1⁺CD4⁺ T cells than infection non-sepsis patients, non-infection critically ill patients, and healthy controls. Among 263 sepsis patients, 56 died within 28 days. LASSO identified five predictors: CD64, HBP, mNAP, PD-1⁺CD4⁺ T cells, and SOFA score. The combined SOFA-integrated immune model achieved an apparent AUC of 0.930 and a bootstrap-corrected AUC of 0.918, with good calibration. Conclusion:The proposed model provides an exploratory, internally validated framework for 28-day mortality risk stratification in sepsis and requires external validation before clinical application.
Objective:To develop and temporally validate an admission-variable model for estimating the risk of persistent inflammation-immunosuppression-catabolism syndrome (PICS) among patients with sepsis who remained in the intensive care unit (ICU) for ≥14 days. Methods:We conducted an ambispective, single-center cohort study. The retrospective development cohort included patients admitted from January 2023 to May 2025, and the prospective temporal validation cohort included patients admitted from June 2025 to February 2026. Candidate predictors measured at ICU admission were selected using least absolute shrinkage and selection operator (LASSO) regression and entered into a multivariable logistic regression model. Discrimination, calibration, and potential clinical utility were evaluated using the area under the receiver operating characteristic curve (AUC), calibration analyses, and decision curve analysis. Results:The development cohort included 242 patients, of whom 93 (38.4%) met the PICS criteria. Compared with respiratory infection, urinary infection (adjusted odds ratio (aOR 0.07, 95% CI 0.01-0.67), gastrointestinal infection (aOR 0.15, 95% CI 0.05-0.45), and skin or soft-tissue infection (aOR 0.29, 95% CI 0.11-0.77) were associated with lower odds of PICS. Higher lactate was associated with higher odds of PICS (aOR 1.20, 95% CI 1.07-1.34), whereas higher lymphocyte count (aOR 0.46, 95% CI 0.28-0.77), albumin (aOR 0.92, 95% CI 0.86-0.99), and vitamin D (aOR 0.88, 95% CI 0.83-0.94) were associated with lower odds. The AUC was 0.803 (95% CI 0.747-0.859) in the development cohort and 0.791 (95% CI 0.718-0.864) in the temporal validation cohort. Conclusion:Among patients with sepsis who remained in the ICU for ≥14 days, an admission-variable model showed acceptable discrimination in the development and temporal validation cohorts. External multicenter validation and prospective impact evaluation are required before clinical use.
Background:Ciprofloxacin resistance among Gram-negative bacteria causing osteomyelitis is an emerging clinical concern that may negatively influence disease severity and patient outcomes. This study sought to assess the burden, independent predictors, and clinical impact of ciprofloxacin resistance in acute Gram-negative osteomyelitis. Methods:A retrospective analysis was performed on patients with acute Gram-negative osteomyelitis between 2019-2024. Clinical, microbiological, laboratory, and outcome variables were compared between ciprofloxacin-resistant and susceptible cohorts. Univariable binary logistic regression analyses were performed to identify factors associated with ciprofloxacin resistance, followed by multivariable binary logistic regression analysis to identify independent predictors. Statistical significance was considered at p-value <0.05 (two-tailed). Results:Antimicrobial resistance patterns were assessed among 279 Gram-negative isolates, while clinical and outcome analyses were conducted among 256 patients. The overall prevalence of ciprofloxacin resistance was 54.5% among Gram-negative isolates. In the univariable binary logistic regression analysis, ciprofloxacin resistance was significantly associated with chronic heart disease (p = 0.03), lower hemoglobin concentration (p = 0.04), hypoalbuminemia (p = 0.0001), and increased inflammatory biomarkers, including c-reactive protein (CRP; p = 0.001), and neutrophil-to-lymphocyte ratio (NLR; p = 0.04). Osteomyelitis caused by ESBL-producing pathogens was also significantly associated with ciprofloxacin resistance (OR = 3.93, 95% CI: 1.87-8.31; p = 0.0001). In the multivariable analysis, hypoalbuminemia (adjusted odds ratio [AOR] = 0.53, 95% confidence interval [CI]: 0.35-0.79; p = 0.002) and infection with ESBL-producing pathogens (AOR = 0.25, 95% CI: 0.11-0.54; p = 0.0001) remained independently associated with ciprofloxacin resistance. Compared with ciprofloxacin-susceptible cohort, ciprofloxacin-resistant patients required significantly more surgical debridement (p = 0.006) and developed higher rates of chronic osteomyelitis (p = 0.005), septic shock (p = 0.03), and in-hospital mortality (p = 0.02). Conclusion:Ciprofloxacin resistance was prevalent among Gram-negative osteomyelitis cases and was associated with greater surgical complexity and poorer clinical outcomes. Early identification of ciprofloxacin-resistant infections and integration of clinical and inflammatory markers may support risk stratification and therapeutic decision-making. Given the retrospective, observational, single-center design, these findings should be interpreted cautiously and validated in larger multicenter studies.
Purpose:Diagnosing tuberculous osteoarticular infections (TB-OAI) remains challenging due to frequent false-negative or confounding conventional culture results. This study evaluated the diagnostic and therapeutic utility of metagenomic next-generation sequencing (mNGS) for occult TB-OAI in patients presenting with negative or misleading culture outcomes. Patients and Methods:We retrospectively analyzed 13 patients with confirmed TB-OAI, encompassing periprosthetic, fracture-related, and native joint infections. Patients were stratified by conventional culture results into strictly culture-negative (n=8) and culture-confounded (n=5; yielding non-mycobacterial organisms) groups. A composite reference standard of mNGS positivity combined with histopathological or clinical validation established the definitive diagnosis. We assessed diagnostic yield, therapeutic modifications, and clinical outcomes. Results:Conventional culture failed to identify Mycobacterium tuberculosis in all 13 cases (0% sensitivity) and yielded misleading non-mycobacterial flora in 5 cases (38.5%). Conversely, mNGS successfully identified the pathogen in 100% (13/13) of patients, corroborated by histopathology in all cases. Consequently, mNGS results changed clinical management from empirical antibiotics to targeted anti-tuberculosis therapy in all cases (100%). Postoperative erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels decreased significantly (P < 0.05). Over a mean follow-up of 17.5 ± 3.0 months, 12 patients achieved durable infection eradication. One patient experienced early recurrence requiring a two-stage revision, ultimately achieving successful infection control. Conclusion:mNGS serves as a promising diagnostic rescue tool for occult TB-OAI when conventional cultures are negative or misleading. While limited by sample size, these preliminary findings suggest mNGS effectively guides the transition from empirical to targeted anti-tuberculosis therapy and limits diagnostic delays.
Yuchong Chen,1 Xiaofen Zou,2 Yingyu Zhong,2 Weiwen Luo,1 Xinhui Zou,1 Huanghui Zeng,3 Xianhui Liu41Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, Guangdong, People’s Republic of China; 2Department of Emergency Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, Guangdong, People’s Republic of China; 3Department of Clinical Pharmacy, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, Guangdong, People’s Republic of China; 4Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, Guangdong, People’s Republic of ChinaCorrespondence: Yuchong Chen, Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, Guangdong, People’s Republic of China, Email 13670868721@163.comBackground: Bloodstream infections (BSIs) are a major cause of sepsis and mortality in critically ill patients, yet accurate pathogen identification remains challenging because blood culture has limited sensitivity and delayed turnaround time. This study aimed to evaluate the complementary diagnostic value of blood culture and mNGS for BSIs patients, and to identify distinct inflammatory and coagulation signatures across bacterial, viral, fungal and polymicrobial infections to facilitate rapid early pathogen discrimination.Methods: In this retrospective study, 18,803 patients with suspected BSI admitted between December 2017 and December 2024 were included. Baseline clinical characteristics and blood culture results were collected. Blood culture was performed as first-line testing, whereas mNGS was selectively applied to patients with negative blood cultures or persistent clinically suspected infection to assess its incremental pathogen detection. Differences in pathogen distribution and inflammatory/coagulation biomarkers across pathogen types were analyzed. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of these biomarkers for viral and fungal infections.Results: Compared with blood culture, mNGS provided additional pathogen detection, with newly identified pathogens comprising viruses (33.5%, 184/550), polymicrobial infections (34.9%, 192/550), and fungal pathogens, whereas single bacterial infections accounted for only 14.5% (80/550). Compared with bacterial infections (n=80), viral infections (n=184) were associated with significantly lower procalcitonin (PCT), C-reactive protein (CRP), and fibrinogen (FIB), but higher prognostic nutritional index (PNI) (all p< 0.05). Fungal infections (n=57) showed significantly lower PNI and FIB levels (p< 0.05) than bacterial infections (n=1098). ROC analysis demonstrated moderate discriminatory performance of PCT, CRP, and FIB for viral infections, while PNI and FIB showed comparable predictive value for fungal infections.Conclusion: mNGS complements conventional blood culture by expanding pathogen detection in clinically selected patients, while inflammatory and coagulation biomarkers may assist early etiological assessment and support clinical assessment and antimicrobial decision-making.Keywords: bloodstream infection, metagenomic next-generation sequencing, blood culture, inflammatory biomarkers, coagulation biomarkers, intensive care unit
Wei Zhao,1 Chunlai Feng,1 Yilei Zhang,1 Linlin Wang21Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 2Department of Medicine, Dinfectome Inc, Nanjing, People’s Republic of ChinaCorrespondence: Chunlai Feng, Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China, Tel +86-15961196958, Email chunlai_feng@126.comPurpose: To explore the clinical significance of pulmonary and gut microbiota in patients with bronchiectasis (BE) with invasive pulmonary aspergillosis (BE-IPA). By analyzing cross-domain microbial networks, we aimed to elucidate the bidirectional interaction mechanisms of the gut–lung axis, provide a theoretical basis for clinical diagnosis, and to identify potential candidate biomarkers and inform future mechanistic studies from a microbiomic perspective.Patients and Methods: We retrospectively examined 78 patients with BE, divided into BE without IPA (n = 37) and BE-IPA (n = 41) groups. Bronchoalveolar lavage fluid and anal swabs were collected. Metagenomic next-generation sequencing was used to analyze microbiota diversity, species composition, and metabolic pathways between the groups. Clinical data were evaluated for correlations with specific taxa, and a cross-domain microbial co-occurrence network was constructed.Results: Compared to the BE group, the BE-IPA group exhibited significant differences in pulmonary microbiota β-diversity (P < 0.05) and increased gut microbiota evenness (Shannon and Simpson indices, P < 0.05). Aspergillus and species-level Aspergillus fumigatus were significantly enriched in the BE-IPA group lungs, whereas Parabacteroides and Hoylesella were enriched in the gut. The relative abundance of core gut commensals such as Bacteroides dorei was negatively correlated with Acute Physiology and Chronic Health Evaluation II score. The BE-IPA group showed 17 upregulated gut metabolic pathways (P < 0.05), primarily involving lipopolysaccharide biosynthesis and carbohydrate metabolism. Pulmonary A. fumigatus exhibited negative correlations with gut B. dorei and pulmonary Rothia mucilaginosa.Conclusion: The pulmonary microbiota in the BE-IPA group showed a fungal–bacterial symbiotic network centered on A. fumigatus, whereas gut microbiota presented a bacterial co-occurrence network enriched with Parabacteroides. In patients with BE-IPA, pulmonary and gut microbes were associated with multiple clinical indicators and metabolic pathways. These microbiota signatures may aid in the assessment of disease severity in BE-IPA, with the gut commensal B. dorei emerging as a candidate biomarker and a potential subject for future interventional studies.Keywords: bronchiectasis with invasive pulmonary aspergillosis, lung microbiota, gut microbiota, gut–lung axis, metagenomic next-generation sequencing
Yan Li,1,* Yuyuan Hu,2,* Yuhang Yang,2,* Wen Yuan Li,1,* Minghua Fan,1 Wei Zhang,3 Yanhong Wang11Department of Neurology, Shanxi Bethune Hospital (Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital), Taiyuan, Shanxi, People’s Republic of China; 2Division of Colorectal Surgery, Shanxi Bethune Hospital (Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital), Taiyuan, Shanxi, People’s Republic of China; 3Department of General Surgery, Yuncheng Central Hospital Affiliated to Shanxi Medical University, Yuncheng, Shanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang, Email 979431670@qq.com Yanhong Wang, Email wangyanhong2627@sxbqeh.com.cnAbstract: Anaerobic meningitis is uncommon and may be underrecognized when cerebrospinal fluid (CSF) culture is non-diagnostic, particularly after antimicrobial exposure or when anaerobic collection, transport, and incubation conditions are suboptimal. Metagenomic next-generation sequencing (mNGS) can provide complementary microbiological evidence in selected culture-negative central nervous system (CNS) infections, but low-biomass CSF results require explicit quality-control reporting and careful assessment of contamination and clinical plausibility. We report two culture-negative bacterial meningitis cases in which CSF mNGS showed a Prevotella-dominant anaerobic signal. Prevotella oris was the predominant species-level detection in both cases, accompanied by lower-abundance anaerobic co-detections. Because P. oris was not recovered by culture or independently confirmed by species-specific PCR, the results were classified as mNGS-supported Prevotella-dominant signals rather than confirmed monomicrobial P. oris meningitis. Both patients received case-specific antimicrobial therapy adjusted according to clinical status, serial CSF findings, neuroimaging evolution, and adverse-event monitoring. Case 1 required meropenem re-escalation after radiological progression and recurrent intracranial hypertension, whereas Case 2 improved after escalation to meropenem followed by the documented de-escalation to metronidazole. Both patients achieved favorable functional outcomes. These cases illustrate how CSF mNGS may be used as an adjunct when conventional microbiology is non-diagnostic, while emphasizing that sequencing signals, serial CSF changes, imaging, and treatment response must be interpreted together. The two observations do not establish P. oris causality or a standardized escalation/de-escalation regimen.Keywords: anaerobic meningitis, antimicrobial decision-making, Prevotella oris, metagenomic next-generation sequencing, culture-negative meningitis, central nervous system infection, case report
Background:Central nervous system (CNS) infections caused by Klebsiella pneumoniae harboring hypervirulence-associated genes usually arise from metastatic dissemination from an extracranial focus. Cases lacking an overt extracranial source remain uncommon. Furthermore, the spontaneous development of tension pneumocephalus in this context is exceptionally rare. Case Presentation:We report a fatal case of a 49-year-old female with a 40-year history of polycystic liver and kidney disease who presented with fulminant meningoencephalitis. Despite aggressive systemic meropenem therapy and neuroprotective measures, she developed refractory intracranial hypertension (780 mmH2O) and rapidly progressive tension pneumocephalus without evidence of neurotrauma or external anatomical breach. Blood and cerebrospinal fluid (CSF) cultures, alongside CSF metagenomic next-generation sequencing (mNGS), identified an extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae. The isolate exhibited a hypermucoviscous phenotype and harbored multiple hypervirulence-associated genes (eg, rmpA, iucA, and iroB) alongside resistance determinants (CTX-M-15-like and AAC(6')-Ib-cr), supporting a probable convergent phenotype. The patient ultimately died from irreversible multiple organ dysfunction syndrome on day 7. Conclusion:The rapid evolution of tension pneumocephalus in this case highlights the potential for abrupt neurological deterioration in CNS infections associated with convergent K. pneumoniae phenotypes. While the exact etiology of intracranial gas is likely multifactorial, this case underscores the critical need to integrate phenotypic assays with molecular diagnostics to identify hypervirulence, while maintaining rigorous differential diagnoses for spontaneous pneumocephalus in the neurocritical care setting.
Background:Bloodstream infections, BSIs caused by Escherichia coli are a major healthcare concern due to the increasing emergence of multidrug-resistant and virulent strains. This study aimed to investigate the phenotypic and genotypic characteristics of bloodstream-derived E. coli isolates, with a focus on antimicrobial resistance, biofilm formation, virulence-associated genes, phylogenetic distribution, and clonal diversity. Methods:A total of 150 blood culture samples were collected from patients with suspected BSIs, of which 60 (40%) E. coli isolates were recovered and confirmed using conventional microbiological methods. Antimicrobial susceptibility testing was performed according to the CLSI2026 guidelines, whereas biofilm formation was assessed using a microtiter plate assay. Virulence genes, phylogenetic groups, and clonal relationships were evaluated using polymerase chain reaction-based, PCR methods. Results:High susceptibility rates were observed for colistin (96.7%) and meropenem (93.3%), whereas the highest rates of resistance were detected against ciprofloxacin (93.3%) and co-trimoxazole (61.7%). Multidrug resistance, MDR was detected in 41.7% of the isolates, while 31.7% were phenotypically characterized as Extended-Spectrum Beta-Lactamase, ESBL producers. Biofilm analysis revealed that 75% of the isolates were capable of biofilm formation. Among the investigated virulence genes, fimH (88.3%), ompT (73.3%), and irp2 (58.3%) were most prevalent. Phylogenetic analysis revealed a predominance of groups B2 (26.7%), B1 (23.3%), and D (23.3%). The ERIC-PCR analysis classified the isolates into 26 distinct ERIC types, indicating substantial genetic diversity. Conclusion:The coexistence of virulence-associated genes, biofilm-forming ability, antimicrobial resistance, and genetic diversity among bloodstream-derived E. coli isolates highlights the circulation of potentially high-risk lineages in healthcare environments. These observations underscore the necessity for ongoing molecular epidemiological monitoring and the implementation of effective infection control strategies.
Chenhao Wei,1,* Rui Wang,1,* Xiuying Zhang,2 Mengfei Yang,1 Shiyao Zhang,1 Hangyu Zhao,1 Lai Zhang11First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, People’s Republic of China; 2Department of Pediatrics, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiuying Zhang, Department of Pediatrics, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China, Email Zxy0909Y@163.comPurpose: To explore the mechanisms of Maxing Shigan Decoction (MXSGD) in community-acquired pneumonia (CAP) via network pharmacology, machine learning, molecular docking, and experimental validation.Methods: MXSGD active compounds and targets were collected from TCMSP and TCM-ID; CAP-related genes were obtained from GEO datasets, and integrated with targets from GeneCards, OMIM, DisGeNET, and TTD. Overlapping targets were subjected to PPI, GO, and KEGG analyses. LASSO and SVM-RFE were used to select feature genes, and six core targets with robust diagnostic performance (AUC > 0.8 in both training and validation sets) were identified after ROC evaluation. Immune infiltration, GSEA, molecular docking, and 100 ns molecular dynamics simulations were performed. In vivo, the efficacy of MXSGD was assessed in a clinically relevant influenza A virus–Streptococcus pneumoniae co-infection mouse model by measuring lung index, histopathology, serum IL-6 and TNF-α levels by ELISA, and mRNA expression by qRT-PCR.Results: We obtained 139 active compounds, 867 MXSGD targets, and 4,444 CAP genes, yielding 262 shared targets enriched in immune-inflammation pathways. Six core targets with high diagnostic accuracy were identified: ABCB1 (AUC = 0.9072), KIT (AUC = 0.8072), PLA2G7 (AUC = 0.8391), SLC2A3 (AUC = 0.9372), PRF1 (AUC = 0.8082), and GPR18 (AUC = 0.8414). Immune infiltration revealed eight differentially abundant immune cell types. Molecular docking and molecular dynamics supported the stable binding of glabridin to KIT and SLC2A3. In vivo, MXSGD significantly ameliorated lung pathological injury, reduced lung index and serum IL-6 and TNF-α levels (FDR-adjusted P < 0.001), and partially reversed mRNA expression changes of KIT, GPR18, and SLC2A3 (FDR-adjusted P < 0.05), while changes in ABCB1, PLA2G7, and PRF1 showed a trend without statistical significance.Conclusion: These results suggest that MXSGD may exert immunomodulatory and anti-inflammatory effects in CAP, potentially by regulating ABCB1, KIT, PLA2G7, SLC2A3, PRF1, and GPR18; however, only three of these (KIT, GPR18, and SLC2A3) showed statistically significant mRNA changes. These findings provide a multi-component, multi-target rationale requiring further experimental and clinical confirmation.Keywords: community-acquired pneumonia, Maxing Shigan Decoction, network pharmacology, machine learning, immune regulation, targets
Chuan Sun,1,* Xiao Zheng,2,* Hui Wang,2 Shaoling Xu11Department of Medical Affairs, Zhaoyuan Hospital of Traditional Chinese Medicine, Yantai, Shandong, People’s Republic of China; 2Department of Critical Care Medicine, Zhaoyuan People’s Hospital, Yantai, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Wang, Email 861280414@qq.com Shaoling Xu, Email 1085518636@qq.comBackground: Low-Molecular-Weight Heparin (LMWH) is a widely used anticoagulant in clinical practice during the COVID-19 pandemic. However, the risk of adverse reactions increases significantly in patients with multiple underlying diseases and immune dysfunction. This article reports a case of a patient with COVID-19 complicated with rheumatoid arthritis who had long-term oral prednisone (5 mg/d) for rheumatoid arthritis, who developed a rare giant hematoma (15cm× 15cm) after LMWH administration, which rapidly progressed to sequential infections caused by multidrug-resistant organisms, including extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and carbapenem-resistant Acinetobacter baumannii (CRAB), within one day. This case describes the complexity and severity of adverse drug reactions under the superposition of multiple factors, and offers clinical insights for diagnosis and management.Case Summary: A 61-year-old female patient was admitted to the hospital for treatment of "viral pneumonia and COVID-19”. Her underlying diseases included rheumatoid arthritis (long-term oral prednisone 5mg/d), hypertension, and type 2 diabetes mellitus. After admission, the patient was given subcutaneous injection of LMWH (2500 IU, qd) for anticoagulation, combined with Simnotrelvir/Ritonavir for antiviral treatment. On the 9th day of medication, a giant hematoma of about 15cm× 15cm appeared at the LMWH injection site; on the 10th day of medication, the hematoma rapidly developed into severe soft tissue infection, and the infection further spread to both waists. Etiological examination successively detected extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and carbapenem-resistant Acinetobacter baumannii (CRAB). The total length of hospital stay was 84 days (excluding 2 days of outpatient observation during inter-hospital transfers). During this period, the patient received multiple rounds of anti-infective treatment with meropenem, linezolid, minocycline, etc. and underwent 5 debridements, Vacuum Sealing Drainage (VSD), and skin grafting. After active treatment, the patient’s infection was finally effectively controlled, and she was discharged smoothly after wound healing.Conclusion: Under the superposition of multiple immunosuppressive factors such as COVID-19, long-term prednisone use and additional in-hospital glucocorticoid therapy, conventional-dose LMWH can induce an unusually large hematoma (15cm× 15cm), with rapid disease progression (secondary infection within 1 day), which is prone to refractory MDROs infection. For such high-risk patients, clinical practice should formulate highly individualized anticoagulant treatment plans and further strengthen the monitoring of adverse reactions.Keywords: low-molecular-weight heparin, adverse drug reaction, giant hematoma, rapid progression, COVID-19, rheumatoid arthritis, glucocorticoids, multidrug-resistant organisms, MDROs
Background:Elderly patients are more susceptible to pulmonary aspergillosis(PA) and exhibit worse clinical outcomes. This study aims to compare the clinical characteristics, pathogen distribution, co-infection patterns, and outcomes of elderly and non-elderly patients with PA diagnosed via targeted next-generation sequencing (tNGS). Methods:This retrospective study included 107 patients with tNGS-confirmed pulmonary aspergillosis admitted to Ruijin Hospital between March 2023 and January 2025. Demographic, clinical, radiological, and laboratory data were extracted from electronic medical records to compare the clinical and microbiological profiles between the elderly (≥65 years) and non-elderly (<65 years) cohorts. Results:A total of 107 patients including elderly (n=64) and non-elderly (n=43) were included retrospectively. The prevalence of invasive pulmonary aspergillosis was significantly higher in the elderly group compared to the non-elderly group (93.8% vs 74.4%). Similarly, the elderly group had significantly higher proportions of overall co-infection (79.7% vs 51.2%), bacterial co-infection (68.8% vs 39.5%), and atypical imaging features such as patchy infiltrates/consolidation (89.1% vs 62.8%) (all P < 0.05). Furthermore, the elderly exhibited significantly lower lymphocyte and albumin levels, and higher D-dimer levels (P < 0.05). Mortality was also significantly higher among elderly patients (18.8% vs 4.7%; P = 0.042). Conclusion:Within our study scope, pulmonary aspergillosis in the elderly is characterized by higher mortality, atypical imaging, prevalent bacterial co-infections, and specific laboratory deviations-most notably, diminished lymphocytes and albumin alongside elevated D-dimer and LDH levels. Furthermore, tNGS serves as a valuable adjunctive tool to identify complex mixed pathogens and assist in clinical management.
