Abstract Background Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder of obscure etiology and limited treatment options, possibly linked to dysregulation in lipid metabolism. While several observational studies suggest that lipid-lowering agents may decrease the risk of IPF, the evidence is inconsistent. The present Mendelian randomization (MR) study aims to determine the association between circulating lipid traits and IPF and to assess the potential influence of lipid-modifying medications for IPF. Methods Summary statistics of 5 lipid traits (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, apolipoprotein A, and apolipoprotein B) and IPF were sourced from the UK Biobank and FinnGen Project Round 10. The study’s focus on lipid-regulatory genes encompassed PCSK9, NPC1L1, ABCG5, ABCG8, HMGCR, APOB, LDLR, CETP, ANGPTL3, APOC3, LPL, and PPARA. The primary effect estimates were determined using the inverse-variance-weighted method, with additional analyses employing the contamination mixture method, robust adjusted profile score, the weighted median, weighted mode methods, and MR-Egger. Summary-data-based Mendelian randomization (SMR) was used to confirm significant lipid-modifying drug targets, leveraging data on expressed quantitative trait loci in relevant tissues. Sensitivity analyses included assessments of heterogeneity, horizontal pleiotropy, and leave-one-out methods. Results There was no significant effect of blood lipid traits on IPF risk (all P＞0.05). Drug-target MR analysis indicated that genetic mimicry for inhibitor of NPC1L1, PCSK9, ABCG5, ABCG8, and APOC3 were associated with increased IPF risks, with odds ratios (ORs) and 95% confidence intervals (CIs) as follows: 2.74 (1.05–7.12, P = 0.039), 1.36 (1.02–1.82, P = 0.037), 1.66 (1.12–2.45, P = 0.011), 1.68 (1.14–2.48, P = 0.009), and 1.42 (1.20–1.67, P = 3.17×10-5), respectively. The SMR method identified a significant association between PCSK9 gene expression in whole blood and reduced IPF risk (OR = 0.71, 95% CI: 0.50–0.99, P = 0.043). Sensitivity analyses showed no evidence of bias. Conclusions Serum lipid traits did not significantly affect the risk of idiopathic pulmonary fibrosis. Drug targets MR studies examining 12 lipid-modifying drugs indicated that PCSK9 inhibitors could dramatically increase IPF risk, a mechanism that may differ from their lipid-lowering actions and thus warrants further investigation.

Accurately identifying viruses from bacteria determine the therapy and outcome of patients suffering from pneumonia. This study focuses on exploring the capability of machine learning techniques in detecting the well-known influenza virus pneumonia from bacterial pneumonia based on the key variable quantity of blood tests and computer tomography (CT). In this study, we propose an improved Harris hawk’s optimization (GSHHO) based on the Gaussian mutation mechanism and simulated annealing method, and then combine GSHHO with Fuzzy k-nearest neighbor (FKNN) to form a GSHHO-FKNN machine learning model, GSHHO-FKNN. The experimental results have demonstrated that the proposed GSHHO-FKNN has identified that ground grass opacity (GGO) and bronchovascular bundle were distinctive CT phenomenon of influenza pneumonia. Furthermore, the number of procalcitonin (PCT) and white blood cells (WBC) in the cases of influenza pneumonia were notable from those in the cases of bacterial pneumonia. In addition, an interesting result was that the absolute value of eosinophils, platelet and flake shadow in influenza pneumonia cases was more abnormal than those of bacterial pneumonia cases. It proved that the GSHHO-FKNN model was an effective method for discriminating influenza pneumonia from community acquired pneumonia, leading to accurate diagnosis against pathogenic microorganisms.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) causing Bloodstream infection (BSI) are associated with high rates of mortality. Nevertheless, only a few studies regarding the epidemiology of CRKP BSI in south China. The purpose of this study was to describe the epidemiology, clinical characteristics, and the mortality of risk factors associated with CRKP causing bloodstream infection. Methods: A retrospective study of patients with CRKP BSI was recruited from teaching hospital in south China from January 2016 to December 2018. Clinical data were collected from medical records. Results: In total, 90 patients with CRKP BSI were enrolled in the study, while 57% (51/90) of the CRKP BSI were obtained from ICU. Most CRKP BSIs originated from hospitals (81; 85%), while the rest (9; 10%) were healthcare-associated. In univariate analysis, gastrointestinal hemorrhage (p=0.029), Pitt bacteremia score (P=0.045), Charlson comorbidity index (p=0.018) and Corticosteroids use (p=0.036) and Septic shock (p=0.001) were associated with the risk factors for mortality. In a multivariate analysis, septic shock (adjusted odds ratio [aOR] 5.591, 95% confidence interval [CI] 1.405-22.246, P=0.015) and Corticosteroids use (aOR 4.148, 95% CI 1.331-12.928, P=0.014) were independently predictors of mortality. Conclusion: Our data showed that the morbidity and mortality of CRKP BSIs patient from ICU and non-ICU was no significant difference. Standardizing operation and improving nurse quality may play an important role in CRKP BSI patient in intensive care unit. Septic shock and Corticosteroids use were the independent factors of CRKP BSI patient mortality. However, the study did not show an association between invasive procedures and the development of CRKP BSI.

Background Patients with lymphoma are at risk for developing pulmonary opportunistic infections due to immunocompromise. However, clinical reports of concurrent lymphoma and opportunistic infection at presentation are rare and often confined to single cases. A delayed diagnosis of either opportunistic infection or lymphoma usually occurs in this complex situation. Here, we report such a case and analyse 18 similar cases searched in the PubMed database to deepen clinicians’ understanding. Case presentation A 48-year-old man presented with a 3-month history of fever, cough and emaciation. High-resolution computed tomography revealed bilateral cavitating lesions of different sizes. Aspergillus fumigatus complex was identified from a bronchoalveolar lavage fluid culture. However, antifungal treatment combined with multiple rounds of antibacterial therapy was unsuccessful, and the patient’s lung lesions continued to deteriorate. Multiple puncture biopsies finally confirmed the coexistence of diffuse large B-cell lymphoma. Despite the initiation of combination chemotherapy, the patient died of progressive respiratory failure. Conclusions Synchronous pulmonary lymphoma and simultaneous opportunistic infection is rare and usually lacks specific clinical and imaging manifestations. Lymphoma should be considered as part of the differential diagnosis of patients with an opportunistic infection when treatment fails or other symptoms are present that could be considered “atypical” for the condition. Tissue biopsy is the gold standard, and multiple biopsies are essential for making the final diagnosis and should be performed upon early suspicion.

Patients with lymphoma are at risk for developing pulmonary opportunistic infections due to immunocompromise. However, clinical reports of concurrent lymphoma and opportunistic infection at presentation are rare and often confined to single cases. A delayed diagnosis of either opportunistic infection or lymphoma usually occurs in this complex situation. Here, we report such a case and analyse 18 similar cases searched in the PubMed database to deepen clinicians' understanding.A 48-year-old man presented with a 3-month history of fever, cough and emaciation. High-resolution computed tomography revealed bilateral cavitating lesions of different sizes. Aspergillus fumigatus complex was identified from a bronchoalveolar lavage fluid culture. However, antifungal treatment combined with multiple rounds of antibacterial therapy was unsuccessful, and the patient's lung lesions continued to deteriorate. Multiple puncture biopsies finally confirmed the coexistence of diffuse large B-cell lymphoma. Despite the initiation of combination chemotherapy, the patient died of progressive respiratory failure.Synchronous pulmonary lymphoma and simultaneous opportunistic infection is rare and usually lacks specific clinical and imaging manifestations. Lymphoma should be considered as part of the differential diagnosis of patients with an opportunistic infection when treatment fails or other symptoms are present that could be considered "atypical" for the condition. Tissue biopsy is the gold standard, and multiple biopsies are essential for making the final diagnosis and should be performed upon early suspicion.

Carboxypeptidase A4 (CPA4) is a member of the metallocarboxypeptidase family. A previous study indicated that CPA4 may participate in the modulation of peptide hormone activity and hormone-regulated tissue growth and differentiation. However, the role of CPA4 in lung tumorigenesis remains unclear. Our study revealed that CPA4 expression was higher in both lung cancer cells and tumor tissues. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays, colony-formation assays, and Cellomics ArrayScan Infinity analysis to demonstrate that CPA4 knockdown inhibited non small-cell lung cancer (NSCLC) cell proliferation. Conversely, ectopic expression of CPA4 enhanced lung cancer cell proliferation. Consistent with these observations, we generated xenograft tumor models to confirm that CPA4 downregulation suppressed NSCLC cell growth. Mechanistically, we revealed that CPA4 downregulation may induce apoptosis and G1-S arrest by suppressing the protein kinase B/c-MYC pathway. These results suggest that CPA4 has an oncogenic effect on lung cancer growth. Taken together, we identified a novel gene in lung cancer that might provide a basis for new therapeutic targets.