IntroductionAcinetobacter baumannii is a major multidrug-resistant pathogen for which effective preventive strategies are urgently needed. This study aimed to characterize the global research landscape, knowledge structure, and emerging trends in Acinetobacter baumannii vaccine research.MethodsPublications from 2011 to 2025 were retrieved from the Web of Science Core Collection and Scopus. After integration, deduplication, and independent screening, 243 publications were included. Bibliometric and visualization analyses were performed using bibliometrix, CiteSpace, and VOSviewer.ResultsResearch output showed an overall nonlinear increase, with an annual growth rate of 18.68%. Iran, China, and the United States were the leading contributors, whereas international collaboration accounted for 19.75% of publications. Keyword analysis identified seven major thematic clusters centered on outer membrane vesicles, bacterial antigens, antimicrobial resistance, computational approaches, and immunization strategies. Temporal analyses showed increasing attention to bioinformatics, reverse vaccinology, peptide/epitope-based design, and virulence-associated targets. Citation analysis further highlighted OMV/OMC-based vaccination and several defined antigens as important components of the field’s intellectual foundation.DiscussionOverall, Acinetobacter baumannii vaccine research has progressively diversified toward increasingly defined, multicomponent, and computationally guided strategies. However, antigenic heterogeneity, limited cross-strain validation, and variability in preclinical evaluation remain major translational challenges. Future efforts should emphasize conserved antigen prioritization, standardized validation, and broader international collaboration to advance promising candidates toward clinical application.
Background: Patients with coexisting lung cancer and COPD are highly susceptible to unplanned readmissions. This study aimed to develop and internally validate a robust predictive nomogram based on the "inflammation-nutrition-tumor" framework to quantify this risk. Methods: A retrospective cohort of 207 clinical episodes from male patients with lung cancer and COPD was analyzed. Participants were categorized into Planned Readmission (PR, n = 165) and Unplanned Readmission (UR, n = 42) groups. Independent risk factors were identified via univariate and multivariable analyses using Generalized Estimating Equations (GEE). A nomogram was subsequently constructed, and its performance was rigorously evaluated using the Area Under the Curve (AUC), calibration plots, and Decision Curve Analysis (DCA). Results: Multivariable GEE analysis demonstrated that the Systemic Immune-Inflammation Index (SII) was a highly significant independent risk factor (OR for a 500-unit increase = 1.490, 95% CI: 1.234-1.798, p < 0.001). Advanced cancer stage (III-IV) was also a significant predictor (OR = 3.590, 95% CI: 1.301-9.909, p = 0.014), while prealbumin (OR = 0.950, 95% CI: 0.896-1.007, p = 0.087) was identified as a key nutritional predictor. The integrated four-variable nomogram (age, cancer stage, SII, prealbumin) demonstrated good discriminative ability with an AUC of 0.809 (95% CI: 0.733-0.885). The calibration plot indicated excellent agreement, and DCA confirmed a substantial clinical net benefit. Conclusions: This SII-based nomogram provides a reliable and practical tool for individualized risk stratification, facilitating targeted clinical interventions to mitigate unplanned readmission rates in this vulnerable population.
The development of vaccines represents a promising and safe strategy to combat multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. In this study, we designed and evaluated a dendritic cell (DC)-targeting multiepitope peptide-based biomimetic nanovaccine for its immunogenicity and protective efficacy in a murine model. Bioinformatics tools were employed to predict and screen B- and T-cell epitopes derived from the OmpW protein of A. baumannii, followed by immunological validation. The dominant epitopes were sequentially linked using 6-aminocaproic acid to synthesize a multiepitope peptide, rOmpW. Subsequently, rOmpW was encapsulated within polylactic-co-glycolic acid (PLGA) nanoparticles coated with neutrophil membranes (NM), and the surface was functionalized with a DC-targeting peptide (DCpep) to construct the biomimetic nanovaccine, DCpep-NM-PLGA-rOmpW. This biomimetic nanovaccine elicited robust Th1 and Th17 cellular immune responses, as well as humoral immunity, and demonstrated significant protective efficacy in a murine model of acute lethal pneumonia caused by A. baumannii. These findings underscore the translational potential of this biomimetic nanovaccine as a prophylactic strategy against A. baumannii infections.
IntroductionAcinetobacter baumannii (A. baumannii) is a major pathogen responsible for hospital-acquired bloodstream infections, with multidrug-resistant (MDR) strains posing severe therapeutic challenges. Neonates are particularly vulnerable, with infections often associated with high morbidity and mortality. Thisstudy aimed to compare the genomic and phenotypic characteristics of A. baumannii isolates from children and adults.MethodsA total of 77 blood isolates of A. baumannii were collected, including 42 from children and 35 from adults. Antimicrobial susceptibility testing against 14 agents was performed. Whole-genome sequencing (WGS) was used for multilocus sequence typing (MLST), antimicrobial resistance gene and virulence gene detection, and phylogenetic analysis based on core-genome single-nucleotide polymorphisms (SNPs). Key resistance mechanisms (β-lactamase production and multidrug efflux pumps) and virulence factors (porins, lipopolysaccharides, metal acquisition systems, and secretion systems) were examined.ResultsCarbapenem resistance was significantly higher in pediatric isolates (97.6%) compared with adult isolates (65.7%). Adult isolates exhibited greater diversity in OXA-type carbapenemases. Virulence gene analysis revealed widespread distribution of porins, lipopolysaccharide synthesis genes, metal acquisition systems, and type VI secretion system components in both groups, with a higher detection rate in pediatric isolates. The majority of isolates belonged to ST2 (89.6%) and carried the blaOXA-23 gene, while ST466 and ST57 were exclusively identified in adult isolates.ConclusionThese findings demonstrate age-related differences in the resistance and virulence profiles of A. baumannii bloodstream isolates. Pediatric isolates exhibited higher carbapenem resistance and virulence gene prevalence, whereas adult isolates showed greater clonal diversity. This comparative analysis enhances understanding of A. baumannii pathogenesis across age groups and provides insights for guiding empirical therapy and strengthening infection control strategies.
Acinetobacter baumannii has become a challenge to treat clinically because of the increased number of extensively drug-resistant strains. Vaccination is an effective way to prevent and control A. baumannii infection. In this study, we constructed an A. baumannii nanovaccine Chitosan-PLGA-rOmp22 (CS-PLGA-rOmp22), and evaluated its immunogenicity and protective effects after intranasal immunization. BALB/c mice that received intranasal immunization with the CS-PLGA-rOmp22 nanovaccine displayed long-lasting local mucosal and systemic immunity, and could resist A. baumannii challenge. The CS-PLGA-rOmp22 penetrated the nasal mucosa and promoted the maturation and activation of dendritic cells (DCs) in vitro. Moreover, the immunoprotective effect of intranasal vaccination was comparable to that of subcutaneous immunization. Our findings suggest that this nanovaccine is a potential candidate for preventing A. baumannii infection after mucosal administration.
Inflammasome-mediated pyroptosis and cytokine release are crucial host defenses against intracellular pathogens. Mycobacterium tuberculosis (M. tb) is a successful intracellular pathogen, and it is largely unclear how it evades immune clearance and persists in macrophages. This study investigated whether the Rv2647 protein acts as a key virulence factor of M. tb and explored the potential mechanism of inhibiting macrophage pyroptosis and promoting M. tb survival. The results showed Rv2647 promoted NLRP3 degradation via enhancing its ubiquitination, which led to the inactivation of NLRP3/caspase-1/GSDMD and reduction of IL-1β secretion, thereby inhibiting macrophage pyroptosis and facilitating M. tb survival. Furthermore, Rv2647-mediated enhancement of NLRP3 ubiquitination and degradation depended on its binding to ISG15, competitively inhibiting ISGylation of NLRP3. The study identified Rv2647 as the key virulence factor that promoted M. tb survival by inhibiting macrophage pyroptosis, whose mechanism was to competitively inhibit the ISGylation of NLRP3 and enhance its ubiquitination, thus suppressing NLRP3/caspase-1/GSDMD-mediated pyroptosis. This finding highlighted Rv2647 as a promising drug target or vaccine antigen for tuberculosis prevention and control.
Pseudomonas aeruginosa (P. aeruginosa), a common opportunistic pathogen, is highly prone to chronic infection and is almost impossible to eradicate, especially attributed to virulence factors and adaptive mutations. In the present study, pseudomonas effector candidate 1 (Pec 1), a novel virulence factor of P. aeruginosa, was investigated, which inhibited bacterial clearance by the host and aggravated lung injury. Further, it demonstrated that Pec 1 inhibited miR-155 via suppressing integrin β3 expression, thereby activating PI3K-AKT-mTOR and inhibiting autophagy in macrophages. Additionally, the identification of Pec 1 in sputum was related to the bacterial load and assisted in rapid diagnosis of P. aeruginosa infection. This finding underlined the importance of Pec 1 in the pathogenesis of P. aeruginosa infection and indicated that Pec 1 could be a vital independent virulence factor during chronic infection with P. aeruginosa, providing new insights in rapid diagnosis, therapeutic targets, and vaccine antigens of P. aeruginosa infection.
Lung cancer is one of the most malignant tumors with fastest morbidity and mortality. Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with early metastasis and poor prognosis. At present, there is a lack of effective indicators to predict prognosis of SCLC patients. Delta-like 3 protein (DLL3) is selectively expressed on the surface of SCLC and is involved in proliferation and invasion. Neuron-specific enolase (NSE) is an enolase isoenzyme that is generally regarded as a biomarker for SCLC and may correlate with stage of SCLC, prognosis and chemotherapy response. NSE can be influenced by different types of factors. To explore the associations between expression levels of DLL3 in tumor tissues with platinum/etoposide chemotherapy response, and assess the prognostic values of DLL3, NSE and other potential prognostic factors in advanced SCLC patients were herein studied. Ninety-seven patients diagnosed with SCLC in Zhongda Hospital from 2014 to 2020 were enrolled in the study. Serum NSE levels were tested using ELISA methods before any treatment. The expression of DLL3 in tumor tissue was detected by Immunohistochemistry (IHC). We investigated the relationship of DLL3 expression with chemotherapy and survival. Progression free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of PFS and OS. DLL3 was detected in 84.5% (82/97) of all patients’ tumor samples by IHC, mainly located on the surface of SCLC cells. Lower DLL3 expression was associated with longer PFS and better chemotherapy response. OS had no significant differences. Multivariate analysis by Cox Hazard model showed that, high DLL3 expression and maximum tumor size >5 cm were independent risk factors for PFS, where NSE < 35 ng/mL and age < 70 were independent prognostic factors for OS. Early stage was independent prognostic factors for PFS and OS (P < .05 log-rank). DLL3 was expressed in the most of SCLCs. DLL3 expression level in the tumor and NSE level in the serum may be useful biomarkers to predict the prognosis of SCLC. DLL3 may be a potential therapeutic target for SCLC in the future.
Novel antimicrobial strategies are urgently needed to treat extensively drug-resistant (XDR) bacterial infections due to the high mortality rate and lack of effective therapeutic agents. Herein, nanoengineered human umbilical cord mesenchymal stem cells (hUC-MSCs), named PMZMU, are designed as a sonosensitizer for synergistic sonodynamic-nano-antimicrobial therapy against gram-negative XDR bacteria. PMZMU is composed of a bacterial targeting peptide (UBI29-41) modified hUC-MSCs membrane (MSCm), a sonosensitizer meso-tetra(4-car-boxyphenyl) porphine doped mesoporous organo-silica nanoparticle and an acidity-responsive metal-organic framework ZIF-8. This innovative formulation enables efficient loading of polymyxin B, reduces off-target drug release, increases circulation and targeting efficacy, and generates reactive oxygen species upon ultrasound irradiation. PMZMU exhibits remarkable in vitro inhibitory activity against four XDR bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (PA), and Escherichia coli. Taking advantage of the bacterial targeting ability of UBI29-41 and the inflammatory chemotaxis of hUC-MSC, PMZMU can be precisely delivered to lung infection sites thereby augmenting polymyxin B concentration. PMZMU-mediated sonodynamic therapy significantly reduces bacterial burden, relieves inflammatory damage by promoting the polarization of macrophages toward M2 phenotype, and improves survival rates without introducing adverse events. Overall, this study offers promising strategies for treating deep-tissue XDR bacterial infections, and guides the design and optimization of biomimetic nanomedicine.
Background The development of vaccines is an effective and safe strategy to combat multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. This study aimed to prepare a DC-targeting multiepitope peptide biomimetic nanovaccine and evaluate its immune response and protective effect in mice. Results The B-cell and T-cell epitopes of the OmpW protein from A. baumannii were predicted and screened using bioinformatics methods and identified by immunological means. The selected dominant epitopes were conjugated in series with 6-aminocaproic acid, and a multiepitope peptide, rOmpW, was chemically synthesized. Then, rOmpW was encapsulated with polylactic-co-glycolic acid (PLGA) and a neutrophil membrane (NM), and the surface was modified with DC-targeting peptide (DCpep) to construct the biomimetic nanovaccine DCpep-NM-PLGA-rOmpW. This biomimetic nanovaccinecan induce strong Th1 and Th17 cellular immune responses and humoral immunity. The biomimetic nanovaccine produced efficient immunological protection in an acute lethal pneumonia model of A. baumannii. Conclusions Our results indicate the potential translational value of this biomimetic nanovaccinefor preventing A.baumannii infection.
Introduction:Primary pleural epithelial angiosarcoma (EAS) is an extremely rare tumor with no specific clinical symptoms. Clinical data on primary pleural EAS are limited, and misdiagnosis often occurs.Case Presentation:The present study reports the case of a 31-year-old patient diagnosed with primary pleural EAS with lung and bone metastases. The patient presented with persistent right chest pain for 5 months and dyspnea for 2 months. Chest computed tomography (CT) scan revealed right hydropneumothorax, diffuse thickening of the right pleura, passive atelectasis, and scattered nodules in the left lung. A medical thoracoscopic pleural biopsy revealed a vasogenic tumor. To further confirm the diagnosis, positron emission tomography/CT (PET/CT) examination was recommended to determine the biopsy site after multidisciplinary discussion. Increased 18F-FDG uptake in the right pleura and hypermetabolic nodules in the right chest wall, first lumbar vertebrae, second sacral vertebrae, and bilateral iliac crest was detected via PET/CT. CT-guided chest wall and lung biopsies were performed. Immunohistochemistry of specific markers was performed according to remote consultation with a pathologist, and tumor cells with strong positive expression of CD31, CD34, and ETS-related genes led to the final diagnosis of primary pleural EAS.Conclusion:Primary pleural EAS should be considered for hydropneumothorax of an unknown cause. PET/CT can accurately locate the lesion. The pathological examination is the basis for primary pleural EAS diagnosis. Moreover, multidisciplinary discussion and remote expert consultation can improve the diagnosis rate of primary pleural EAS.
This review focuses on Acinetobacter baumannii, a Gram-negative bacterium that causes various infections and whose multidrug resistance has become a significant challenge in clinical practices. There are multiple bacterial mechanisms in A. baumannii that participate in bacterial colonization and immune responses. It is believed that outer membrane vesicles (OMVs) budding from the bacteria play a significant role in mediating bacterial survival and the subsequent attack against the host. Most OMVs originate from the bacterial membranes and molecules are enveloped in them. Elements similar to the pathogen endow OMVs with robust virulence, which provides a new direction for exploring the pathogenicity of A. baumannii and its therapeutic pathways. Although extensive research has been carried out on the feasibility of OMV-based vaccines against pathogens, no study has yet summarized the bioactive elements, biological activity, and vaccine applicability of A. baumannii OMVs. This review summarizes the components, biogenesis, and function of OMVs that contribute to their potential as vaccine candidates and the preparation methods and future directions for their development.
BackgroundObservational studies have revealed associations between diet and lung cancer. However, it is unclear whether the association is disturbed by confounding factors. We used a two-sample Mendelian randomization (MR) method to characterize the associations between diet and the lung cancer risk (including 3 subtypes: lung adenocarcinoma (LA), squamous cell lung carcinoma (SqCLC), and small cell lung cancer (SCLC)).Materials and methodsData on 20 diets were screened from the UK Biobank. Lung cancer data came from a large meta-analysis of 85,716 individuals. The inverse-variance weighted method was used as the main analysis. Sensitivity analysis was also used to explain the different multiplicity patterns of the final model.ResultsOur results showed significant evidence that 3 diets were associated with lung cancer [odds ratio (OR): 0.271, 95% confidence interval (CI): 0.150–0.488, p = 1.46 × 10−4, dried fruit; OR: 3.010, 95% CI: 1.608–5.632, p = 5.70 × 10−4, beer] and SqCLC (OR: 0.135, 95% CI: 0.062–0.293, p = 2.33 × 10−5, dried fruit; OR: 0.485, 95% CI: 0.328–0.717, p = 2.9 × 10−4, cheese). There were also suggestive correlations between 5 dietary intakes and lung cancer (OR: 0.441, 95% CI: 0.250–0.778, p = 0.008, cereal; OR: 2.267, 95% CI: 1.126–4.564, p = 0.022, beef), LA (OR: 0.494, 95% CI: 0.285–0.858, p = 0.012, dried fruit; OR: 3.536, 95% CI: 1.546–8.085, p = 0.003, beer) and SCLC (OR: 0.006, 95% CI: 0.000–0.222, p = 0.039, non-oily fish; OR: 0.239, 95% CI: 0.086–0.664, p = 0.006, dried fruit). No other association between diet and lung cancer was observed.ConclusionOur study preliminary found that cheese, dried fruit, and beer intake were significantly associated with the risk of lung cancer or its subtypes, while cereal, beef, and non-oily fish intake were suggestively associated with the risk of lung cancer or its subtypes. Well-designed prospective studies are still needed to confirm our findings in the future.
Recently, development of drug delivery systems for accurate delivery of antitumor drugs to tumor sites to improve their antitumor efficacy has attracted great interest in the area of cancer immunotherapy. In this report, an intelligent biodegradable hollow manganese dioxide (HMnO2) nanoparticle (NP) with a human umbilical cord mesenchymal stem cell (hUC-MSC) membrane coating was designed to exert efficient chemo-immunotherapy for cancer treatment. A TAT peptide-modified membrane structure was constructed for nuclear targeting. Our findings showed that this new nanoreactor inherited the active targeting capability of MSCs and exhibited tumoritropic accumulation significantly at the cancerous parts. Compared with other formulations, intravenous injection of the NPs markedly inhibited tumor growth, relapse, and metastasis. Moreover, we found that the NPs effectively boosted dendritic cell maturation and recruited effector T cells into tumors. Overall, this work demonstrates the great potential of applying MSC membrane-coated manganese dioxide NPs as nucleus-targeting nanocarriers in cancer chemo-immunotherapy.
BackgroundClinical values of metagenomic next-generation sequencing (mNGS) in patients with severe pneumonia remain controversial. Therefore, we conduct this meta-analysis to evaluate the diagnostic performance of mNGS for pathogen detection and its role in the prognosis of severe pneumonia.MethodsWe systematically searched the literature published in PubMed, Embase, Cochrane Library, Web of Science, Clinical Trials.gov, CNKI, Wanfang Data, and CBM from the inception to the 28th September 2022. Relevant trials comparing mNGS with conventional methods applied to patients with severe pneumonia were included. The primary outcomes of this study were the pathogen-positive rate, the 28-day mortality, and the 90-day mortality; secondary outcomes included the duration of mechanical ventilation, the length of hospital stay, and the length of stay in the ICU.ResultsTotally, 24 publications with 3220 patients met the inclusion criteria and were enrolled in this study. Compared with conventional methods (45.78%, 705/1540), mNGS (80.48%, 1233/1532) significantly increased the positive rate of pathogen detection [OR = 6.81, 95% CI (4.59, 10.11, P < 0.001]. The pooled 28-day and 90-day mortality in mNGS group were 15.08% (38/252) and 22.36% (36/161), respectively, which were significantly lower than those in conventional methods group 33.05% (117/354) [OR = 0.35, 95% CI (0.23, 0.55), P < 0.001, I2 = 0%] and 43.43%(109/251) [OR = 0.34, 95% CI (0.21, 0.54), P < 0.001]. Meanwhile, adjusted treatment based on the results of mNGS shortened the length of hospital stay [MD = -2.76, 95% CI (− 3.56, − 1.96), P < 0.001] and the length of stay in ICU [MD = -4.11, 95% CI (− 5.35, − 2.87), P < 0.001].ConclusionThe pathogen detection positive rate of mNGS was much higher than that of conventional methods. Adjusted treatment based on mNGS results can reduce the 28-day and 90-day mortality of patients with severe pneumonia, and shorten the length of hospital and ICU stay. Therefore, mNGS advised to be applied to severe pneumonia patients as early as possible in addition to conventional methods to improve the prognosis and reduce the length of hospital stay.
Acinetobacter baumannii is a gram-negative bacterium and a crucial opportunistic pathogen in hospitals. A. baumannii infection has become a challenging problem in clinical practice due to the increasing number of multidrug-resistant strains and their prevalence worldwide. Vaccines are effective tools to prevent and control A. baumannii infection. Many researchers are studying subunit vaccines against A. baumannii . Subunit vaccines have the advantages of high purity, safety, and stability, ease of production, and highly targeted induced immune responses. To date, no A. baumannii subunit vaccine candidate has entered clinical trials. This may be related to the easy degradation of subunit vaccines in vivo and weak immunogenicity. Using adjuvants or delivery vehicles to prepare subunit vaccines can slow down degradation and improve immunogenicity. The common immunization routes include intramuscular injection, subcutaneous injection, intraperitoneal injection and mucosal vaccination. The appropriate immunization method can also enhance the immune effect of subunit vaccines. Therefore, selecting an appropriate adjuvant and immunization method is essential for subunit vaccine research. This review summarizes the past exploration of A. baumannii subunit vaccines, hoping to guide current and future research on these vaccines.
Pseudomonas aeruginosa (PA) is an important pathogen that has been proven to colonize and cause infection in the respiratory tract of patients with structural lung diseases and to lead to bronchial fibrosis. The development of pulmonary fibrosis is a complication of PA colonization of the airway, resulting from repeated infection, damage and repair of the epithelium. Bronchial epithelial cell epithelial-mesenchymal transition (EMT) plays a vital role in bronchial fibrosis. To date, research on bronchial epithelial cell EMT caused by PA-secreted virulence factors has not been reported. Here, we found that PA3611 protein stimulation induced bronchial epithelial cell EMT with mesenchymal cell marker upregulation and epithelial cell marker downregulation. Moreover, integrin αvβ6 expression and TGF-β1 secretion were markedly increased, and p38 MAPK phosphorylation and NF-κB p65 subunit phosphorylation were markedly enhanced. Further research revealed that PA3611 promoted EMT via integrin αvβ6-mediated TGF-β1-induced p38/NF-κB pathway activation. The function of PA3611 was also verified in PA-infected rats, and the results showed that ΔPA3611 reduced lung inflammation and EMT. Overall, our results revealed that PA3611 promoted EMT via integrin αvβ6-mediated TGF-β1-induced p38/NF-κB pathway activation, suggesting that PA3611 acts as a crucial virulence factor in bronchial epithelial cell EMT and is a potential target for the clinical treatment of bronchial EMT and fibrosis caused by chronic PA infection.
Objective:To evaluate the value of high-throughput sequencing (HTS) technology for bronchoalveolar lavage fluid (BALF) in diagnosing pulmonary infection pathogen and corresponding effects on the prognosis of patients.Methods:A computer retrieval was performed in Pubmed, Embase, Cochrane Library, Wanfang database, Web of Science, clinical trials.gov, CNKI, Wanfang database, and China biology medicine dise (CBM) from the setup date of the database to December 8, 2021.The positive rate, sensitivity and specificity of BALF metagenomic sequencing and traditional pathogen detection method on pulmonary infection detection were compared.The intensity of antibiotics used, length of hospital stay, 28/30 day mortality, and 90-day mortality were compared by adjusting the therapeutic regimen according to pathogenic test results.Review Manager 5.4.1 software was used for meta-analysis on the abovementioned indexes.Results:A total of 35 papers with 2 624 patients were included, involving 2 248 cases in the HTS group and 2 493 cases in the traditional pathogen detection group.The results of the meta-analysis showed that the positive rate of the HTS group was 79.8%(1 793/2 248), being significantly higher than that of the traditional pathogen detection group at 41.7%(1 039/2 493)( OR=6.84, 95% CI: 4.84~9.67, Z=10.88, P<0.001). The sensitivity, specificity, and the area under the curve of receiver operating characteristic curves by BALF metagenomic sequencing was higher than those by traditional pathogen detection method.The patients enrolled in nine papers were patients with severe pneumonia, and the subgroup analysis showed that the positive rate of BALF high-throughput sequencing in patients with severe pneumonia was 85.8%(495/577), being significantly higher than that in the traditional pathogen detection group at 42.9% (282/657)( OR=6.52, 95% CI: 4.04~10.52, Z=7.69, P<0.001). According to the results of pathogen detection, the intensity of antibiotic use in the high-throughput sequencing group was significantly lower than that in the traditional detection group(SMD=-40.04, 95% CI: -47.05~-33.03, Z=11.19, P<0.001); and the everage length of stay was shortened(SMD=-4.68, 95% CI: -6.12~-3.25, Z=6.40, P<0.001). The 28/30-day mortality and 90-day mortality of the HTS group was 9.09% and 12.82%, respectively, both of which were lower than those of the traditional detection group at 26.44%( OR=0.26, 95% CI: 0.13~0.51, Z=3.89, P<0.001) and 38.30%( OR=0.21, 95% CI: 0.07~0.66, Z=2.67, P=0.008). Conclusions:Compared with traditional pathogen detection methods, using BALF for HTS is found to have higher diagnostic value for pulmonary infection.The adjustment on the therapeutic regimenbased on HTS results for BALFcan reduce the intensity of antibiotic use, shorten the length of hospital stay, reduce mortality, and improve the prognosis of patients.