Background: Pulmonary trichomoniasis is considered a neglected disease due to failures in recognizing it, stemming from insensitive microbial methods and a lack of specific clinical features. This study aims to analyze the clinical implications of trichomonads detected in bronchoalveolar lavage fluid (BALF) by metagenomic next-generation sequencing (mNGS). Methods: This multicenter retrospective study included patients diagnosed with pneumonia, admitted to three tertiary hospitals in China from July 2018 to September 2022, with trichomonads detected in BALF through mNGS. The analysis covered demographics, comorbidities, symptoms, laboratory findings, mNGS results, clinical treatment, and outcomes of these patients. Results: A total of 17 patients were enrolled, comprising 14 males and 3 females. Trichomonas tenax and Trichomonas vaginalis were detected by mNGS in BALF samples of 15 and 2 patients, respectively. Patients were categorized into two groups based on the presence of risk factors for trichomonad infection, including immunocompromised conditions, uncontrolled diabetes mellitus, oral/periodontal diseases, and aspiration. Among 11 patients with risk factors (Case 1-11), 4 received nitromidazoles as part of comprehensive treatment, achieving a 100% treatment success rate. The remaining 7 patients, who did not receive nitromidazoles, had only one achieving relief after broad-spectrum antimicrobial therapy, resulting in a 14.3% treatment success rate. For the 6 patients without any risk factors for trichomonad infection (Case 12-17), none received nitromidazoles during hospitalization. However, 4 out of these 6 patients (66.7%) eventually recovered. Conclusion: mNGS proves to be an efficient tool for detecting trichomonads in BALF samples. Comprehensive analysis of clinical features and laboratory indicators is essential to distinguish between infection and colonization of trichomonads. Pulmonary trichomoniasis should not be overlooked when trichomonads are detected in BALF from patients with risk factors.
High-Throughput Nucleotide Sequencing , Trichomonas Infections , Female , Male , Humans , Retrospective Studies , Bronchoalveolar Lavage Fluid , Risk Factors , Metagenomics , Trichomonas Infections/diagnosis , Sensitivity and Specificity
Background: Phosphaturic mesenchymal tumor (PMT) is a very rare tumor of bone and soft tissue that has no specific clinical manifestations. Here we present 2 cases of PMT in the right thigh, including comparatively adequate immunohistochemistry. Case Presentation: We described 2 cases of PMT in the right thigh with manifestations of hypophosphatemia. PET-CT examination showed that both patients had lesions with increased expression of somatostatin receptors in the right thigh. Bland cells and dirty calcified stroma were exhibited under the microscope. And immunohistochemical detection of FGF-23 was positive. Conclusions: PMT is a very uncommon tumor for which diagnosis and treatment are often delayed. Considering the importance of surgery for the treatment of this disease, a full understanding of its clinicopathological features will facilitate the diagnosis of this disease.
Cancer represents a serious concern for human life and health. Due to drug resistance and the easy metastasis of tumors, there is urgent need to develop new cancer treatment methods beyond the traditional radiotherapy, chemotherapy, and surgery. Bacterial outer membrane vesicles (OMVs) are a type of double-membrane vesicle secreted by Gram-negative bacteria in the process of growth and life, and play extremely important roles in the survival and invasion of those bacteria. In particular, OMVs contain a large number of immunogenic components associated with their parent bacterium, which can be used as vaccines, adjuvants, and vectors to treat diseases, especially in presenting tumor antigens or targeted therapy with small-molecule drugs. Some OMV-based vaccines are already on the market and have demonstrated good therapeutic effect on the corresponding diseases. OMV-based vaccines for cancer are also being studied, and some are already in clinical trials. This paper reviews bacterial outer membrane vesicles, their interaction with host cells, and their applications in tumor vaccines.
Cancer Vaccines , Antigens, Neoplasm , Bacterial Outer Membrane , Bacterial Outer Membrane Proteins , Gram-Negative Bacteria , Humans
Hypervirulent Klebsiella pneumoniae (hvKP) causes invasive infections and leads to high morbidity and mortality rates. Here, we report the case of a Chinese man with diabetes mellitus who developed acute respiratory distress syndrome and septic shock due to hvKP belonging to the K1 strain. The patient was treated with venovenous extracorporeal membrane oxygenation and continuous renal replacement therapy, in combination with antibiotics and recovered well. Clinicians should be aware of fatal infections caused by hvKP and investigate the best treatment options for patients at various stages of infection.
Objective: Lung involvement is a major cause of morbidity and mortality in patients with rheumatic diseases. This study aimed to assess the application value of metagenomic next-generation sequencing (mNGS) for identifying pathogens in patients with rheumatic diseases and diffuse pulmonary lesions. Methods: This retrospective study included patients who were diagnosed with rheumatic diseases and presenting diffuse pulmonary lesions on chest radiography in Xiangya Hospital from July 2018 to May 2022. Clinical characteristics were summarized, including demographics, symptoms, comorbidities, radiological and laboratory findings, and clinical outcomes. Pulmonary infection features of these patients were analyzed. Furthermore, diagnostic performance of mNGS and conventional methods (including smear microscopy, culture, polymerase chain reaction assay, and serum immunological test) in identifying pulmonary infections and causative pathogens were compared. Results: A total of 98 patients were included, with a median age of 58.0 years old and a female proportion of 59.2%. Of these patients, 71.4% showed the evidence of pulmonary infections. Combining the results of mNGS and conventional methods, 129 infection events were detected, including 45 bacterial, 40 fungal and 44 viral infection events. Pulmonary mixed infections were observed in 38.8% of patients. The detection rates of mNGS for any pathogen (71.4% vs 40.8%, P < 0.001) and mixed pathogens (40.8% vs 12.2%, P < 0.001) were higher than that of conventional methods. Moreover, mNGS had a significantly higher sensitivity (97.1% vs. 57.1%, P < 0.001) than conventional methods in identifying pulmonary infections, while its specificity (92.9% vs. 96.4%, P = 0.553) were comparable to conventional methods. Antimicrobial and antirheumatic treatments were markedly modified based on mNGS results in patients with rheumatic diseases and diffuse pulmonary lesions. Conclusions: For patients diagnosed with rheumatic diseases and presenting diffuse pulmonary lesions, mNGS is a powerful complement to conventional methods in pathogen identification due to its high efficiency and broad spectrum. Early application of mNGS can provide guidance for precision treatment, and may reduce mortality and avoid antibiotic abuse.
Pneumonia , Rheumatic Diseases , Anti-Bacterial Agents , Female , High-Throughput Nucleotide Sequencing/methods , Humans , Lung/diagnostic imaging , Middle Aged , Retrospective Studies , Rheumatic Diseases/diagnosis , Sensitivity and Specificity
Pancreatic adenocarcinoma (PAAD) is a malignant tumor with high morbidity and mortality worldwide. Members from the structural maintenance of chromosomes (SMC) gene family function as oncogenes in various tumor types, but their roles in PAAD have not been elucidated. In this study, we aimed to explore the role of the SMC family in tumor progression and cancer immune infiltration in PAAD using integrative bioinformatic analyses. The results showed that the SMC 1A, 2, 3, 4, and 6 were overexpressed in PAAD tissues; of these, SMC 1A, 4, 5, and 6 could be potential prognostic biomarkers for PAAD. The expression of SMC genes was found to be strongly associated with immune cell infiltration. According to the infiltrative status of various immune cells, the mRNA expression of SMC genes in PAAD was associated with the overall and recurrence-free survival of patients. In conclusion, the SMC gene family is associated with PAAD and may be involved in tumorigenesis and cancer-immune interactions; thus, members from this gene family may serve as promising prognostic and therapeutic biomarkers of PAAD.
Background: Although multiple metabolic pathways are involved in the initiation, progression, and therapy of lung adenocarcinoma (LUAD), the tumor microenvironment (TME) for immune cell infiltration that is regulated by metabolic enzymes has not yet been characterized. Methods: 517 LUAD samples and 59 non-tumor samples were obtained from The Cancer Genome Atlas (TCGA) database as the training cohort. Kaplan-Meier analysis and Univariate Cox analysis were applied to screen the candidate metabolic enzymes for their role in relation to survival rate in LUAD patients. A prognostic metabolic enzyme signature, termed the metabolic gene risk score (MGRS), was established based on multivariate Cox proportional hazards regression analysis and was verified in an independent test cohort, GSE31210. In addition, we analyzed the immune cell infiltration characteristics in patients grouped by their Risk Score. Furthermore, the prognostic value of these four enzymes was verified in another independent cohort by immunohistochemistry and an optimized model of the metabolic-immune protein risk score (MIPRS) was constructed. Results: The MGRS model comprising 4 genes (TYMS, NME4, LDHA, and SMOX) was developed to classify patients into high-risk and low-risk groups. Patients with a high-risk score had a poor prognosis and exhibited activated carbon and nucleotide metabolism, both of which were associated with changes to TME immune cell infiltration characteristics. In addition, the optimized MIPRS model showed more accurate predictive power in prognosis of LUAD. Conclusion: Our study revealed an integrated metabolic enzyme signature as a reliable prognostic tool to accurately predict the prognosis of LUAD.
INTRODUCTION: This study aimed to evaluate the utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus-infected patients. METHODS: We conducted a retrospective study. A total of 60 non-human immunodeficiency virus-infected PJP patients and 134 patients diagnosed with non-PJP pneumonia were included. P. jirovecii and other co-pathogens identified by mNGS in bronchoalveolar lavage fluid and/or blood samples were analyzed. Using clinical composite diagnosis as the reference standard, we compared the diagnostic performance of mNGS in PJP with conventional methods, including Gomori methenamine silver staining and serum (1,3)-ß-D-glucan. Modifications of antimicrobial treatment for PJP patients after the report of mNGS results were also reviewed. RESULTS: mNGS reached a sensitivity of 100% in diagnosing PJP, which was remarkably higher than Gomori methenamine silver staining (25.0%) and serum (1,3)-ß-D-glucan (67.4%). The specificity of mNGS (96.3%) significantly surpassed serum (1,3)-ß-D-glucan (81.4%). Simultaneous mNGS of bronchoalveolar lavage fluid and blood samples was performed in 21 out of 60 PJP patients, and it showed a concordance rate of 100% in detecting P. jirovecii. Besides, mNGS showed good performance in identifying co-pathogens of PJP patients, among which cytomegalovirus and Epstein-Barr virus were most commonly seen. Initial antimicrobial treatment was modified in 71.7% of PJP patients after the report of mNGS results. CONCLUSION: mNGS is a useful diagnostic tool with good performance for the diagnosis of PJP and the detection of co-pathogens. mNGS of bronchoalveolar lavage fluid and/or blood samples is suggested in patients with presumptive diagnosis of PJP. Blood samples may be a good alternative to bronchoalveolar lavage fluid for mNGS when bronchoscopic examination is not feasible.
RATIONALE: In 2019, a small HAdV55-associated outbreak of adenovirus infection occurred among the intensive care unit (ICU) staff in Xiangya Hospital of Central South University in Hunan Province, China, during the treatment of a patient. OBJECTIVE: To investigate the characteristics of a nosocomial adenovirus outbreak in an ICU. METHODS: We evaluated all the patients treated and the medical staff working in the ICU from August 1 to September 4, 2019. We further performed an epidemiological and molecular analysis for this outbreak from patient to healthcare workers and between healthcare workers. After the outbreak, we adopted exposure prevention and droplet prevention measures based on standard precautions. MEASUREMENTS AND MAIN RESULTS: Between August 1 and August 27, 2019, 27 cases of human adenovirus cross-infection were reported in our institution. Among the cases, eleven were doctors (41%), eleven were nurses (41%), three were respiratory therapists (11%), and two were caregivers (7%). The attack rate was 28.4%, and the fatality rate was 0. The results showed that contact with the index case, lack of hand hygiene or gloving adherence were risk factors for infection after adenovirus exposure. After taking specific precautions, no new cases of infection have appeared since August 27. CONCLUSIONS: Our results show that HAdV55 in a single patient had strong transmission potential in an intensive care unit with adequate facilities and standardized operation. We provide convincing evidence indicating that attention could be highlighted on the role of standard and specific precautions for controlling the spread of adenovirus in ICUs.
Adenovirus Infections, Human/epidemiology , Cross Infection/epidemiology , Medical Staff/statistics & numerical data , Adenovirus Infections, Human/prevention & control , Adenovirus Infections, Human/virology , Adenoviruses, Human/classification , Adenoviruses, Human/genetics , Adenoviruses, Human/isolation & purification , Adenoviruses, Human/physiology , Adult , China/epidemiology , Cross Infection/prevention & control , Cross Infection/virology , Female , Hand Hygiene , Hospitals, Teaching/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Phylogeny , Tertiary Healthcare/statistics & numerical data , Young Adult
Temporal lobe epilepsy (TLE) is a complex disease with its pathogenetic mechanism still unclear. Single-nucleotide polymorphisms (SNPs) of miRNA (miRSNPs) are SNPs located on miRNA genes or target sites of miRNAs, which have been proved to be associated with neuropsychic disease development by interfering with miRNA-mediated regulatory function. In this study, we integrated TLE-related risk genes and risk pathways multi-dimensionally based on public data resources. Furthermore, we systematically screened candidate functional miRSNPs for TLE and constructed a TLE-associated pathway-based miRSNP switching network, which included 92 miRNAs that target 12 TLE risk pathways. Moreover, we dissected thoroughly the correlation between 5 risk genes of 4 risk pathways and TLE development. Additionally, the biological function of several candidate miRSNPs were validated by luciferase reporter assay. In silico approach facilitates to select potential "miRSNP-miRNA-risk gene-pathway" axis for experimental validation, which provided new insights into the mechanism of miRSNPs as potential genetic risk factors of TLE.
Epilepsy, Temporal Lobe/genetics , Gene Regulatory Networks , Genetic Predisposition to Disease , MicroRNAs/genetics , Polymorphism, Single Nucleotide/genetics , Base Sequence , Genes, Reporter , Humans , Luciferases/metabolism , MicroRNAs/metabolism , Models, Biological , Risk Factors
A binary nanocomposite composed of two-dimensional (2D) ultrathin ZnIn2S4 nanosheets and one-dimension (1D) TiO2 nanobelts was prepared and applied as a noble-metal-free photocatalyst for hydrogen evolution under solar-light irradiation. The TiO2 nanobelt/ZnIn2S4 nanosheet heterojunction nanocomposites show higher light absorption capacity, larger surface area and higher separation of charge carriers in comparison to pristine TiO2 and ZnIn2S4. As a result, the hydrogen production over the TiO2/ZnIn2S4 nanocomposite with 15 wt% TiO2 can reach up to 348.21 µmol · g-1 · h-1, even without noble metals, which is about 26 and 2.3 times higher than the pristine TiO2 and ZnIn2S4, respectively. Meanwhile, a possible photocatalytic mechanism of TiO2/ZnIn2S4 heterojunction nanocomposites was proposed and corroborated by photoluminescence (PL) spectroscopy and photoelectrochemical (PEC) results. This work paves a way for developing low-cost and high-efficiency noble-metal-free photocatalytic systems for solar-to-hydrogen evolution.
