Tetrahedral DNA loaded siCCR2 restrains M1 macrophage polarization to ameliorate pulmonary fibrosis in chemoradiation-induced murine model.

Idiopathic pulmonary fibrosis (IPF) is a chronic lethal disease in the absence of demonstrated efficacy for preventing progression. Although macrophage-mediated alveolitis is determined to participate in myofibrotic transition during disease development, the paradigm of continuous macrophage polarization is still under-explored due to lack of proper animal models. Here, by integrating 2.5 U/kg intratracheal Bleomycin administration and 10 Gy thorax irradiation at day 7, we generated a murine model with continuous alveolitis-mediated fibrosis, which mimics most of the clinical features of our involved IPF patients. In combination with data from scRNA-seq of patients and a murine IPF model, a decisive role of CCL2/CCR2 axis in driving M1 macrophage polarization was revealed, and M1 macrophage was further confirmed to boost alveolitis in leading myofibroblast activation. Multiple sticky-end tetrahedral framework nucleic acids conjunct with quadruple ccr2-siRNA (FNA-siCCR2) was synthesized in targeting M1 macrophages. FNA-siCCR2 successfully blocked macrophage accumulation in pulmonary parenchyma of the IPF murine model, thus preventing myofibroblast activation and leading to the disease remitting. Overall, our studies lay the groundwork to develop a novel IPF murine model, reveal M1 macrophages as potential therapeutic targets, and establish new treatment strategy by using FNA-siCCR2, which are highly relevant to clinical scenarios and translational research in the field of IPF.

Serum ferritin as a significant biomarker for patients with idiopathic inflammatory myopathy-associated interstitial lung disease: A systematic review and meta-analysis.

OBJECTIVE: The biomarkers for predicting the occurrence, progression, and death of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) remain unclear. Serum ferritin (SF) is a potential candidate and this systematic review and meta-analysis aimed to reveal the clinical significance of SF in IIM-ILD. METHODS: Eligible English studies were selected from PubMed, Embase, Web of science and Scopus up to 9 June 2023. The SF levels in patients with IIM-ILD were extracted and pooled. Subgroup analysis was performed based on disease types, sensitivity analysis was conducted by excluding one class of literature at a time, and publication bias was assessed by funnel plot and Egger's test. RESULTS: Pooled analysis of 1,933 patients with IIM from 19 studies showed that SF levels were significantly higher in IIM-ILD group (WMD=263.53ng/mL, 95% CI: 146.44-380.62, p<0.001) than IIM without ILD, subgroup analysis showed that SF levels in DM-ILD (WMD = 397.67ng/mL, 95% CI:142.84-652.50, p = 0.002) and PM/DM-ILD (WMD = 117.68 ng/mL, 95% CI: 86.32-149.04, p < 0.001) were significantly higher compared to those without ILD. SF levels were significantly higher in rapidly progressive interstitial lung disease group (RP-ILD)(WMD = 484.99 ng/mL, 95% CI: 211.12-758.87, p= 0.001) than chronic ILD(C-ILD) group, subgroup analysis showed that SF levels in DM-RP-ILD (WMD= 509.75 ng/mL, 95% CI: 215.34-804.16, p=0.001) were significantly higher than those in DM-C-ILD group. SF levels were significantly higher in death group (WMD= 722.16 ng/mL, 95% CI: 572.32-872.00, p< 0.001) compared to the survival group, subgroup analysis showed that death patients with DM-ILD(WMD= 735.62 ng/mL, 95% CI:574.92-896.32, p<0.001) and PM-ILD (WMD= 632.56 ng/mL, 95% CI:217.92-1047.19, p=0.003) had significantly higher SF levels than survival group respectively. CONCLUSION: Increased SF levels can serve as a biomarker for predicting the occurrence, progression and death of patients with IIM-ILD, which can provide early warning sign for intervention and prognosis evaluation for IIM-ILD patients.

Body mass index and weight loss as risk factors for poor outcomes in patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

OBJECTIVE: The association between nutritional status and prognosis of idiopathic pulmonary fibrosis (IPF) remains unclear. This systematic review and meta-analysis aimed to explore the effect of body mass index (BMI) and weight loss on the prognosis of IPF patients. METHODS: We accumulated studies on IPF, BMI, and weight loss from databases including PubMed, Embase, Web of science, Scopus, Ovid and Cochrane Library up to 4 August 2023. Using Cox proportional hazard regression model for subgroup analysis, hazard ratio (HR) and 95% confidence intervals (CI) for BMI in relation to mortality, acute exacerbation (AE), and hospitalization in IPF patients were calculated, and HR, odds ratio (OR), and 95% CI for weight loss corresponding to IPF patient mortality were assessed. Sensitivity analysis was peformed by eliminating every study one by one, and publication bias was judged by Egger's test and trim-and-fill method. RESULTS: A total of 34 eligible studies involving 18,343 IPF patients were included in the meta-analysis. The pooled results by univariate Cox regression analysis showed that baseline BMI was a predictive factor for IPF mortality (HR = 0.93, 95%CI = [0.91, 0.94]). Furthermore, the results by the multivariable regression model indicated that baseline BMI was an independent risk factor for predicting IPF mortality (HR = 0.94, 95%CI = [0.91, 0.98]). Weight loss was identified as a risk factor for IPF mortality (HR = 2.74, 95% CI = [2.12, 3.54]; OR = 4.51, 95% CI = [1.72, 11.82]) and there was no predictive value of BMI for acute exacerbation (HR = 1.00, 95% CI= [0.93, 1.07]) or hospitalization (HR = 0.95, 95% CI = [0.89, 1.02]). CONCLUSION: Low baseline BMI and weight loss in the course of IPF may indicate a high risk of mortality in patients with IPF, so it is meaningful to monitor and manage the nutritional status of IPF patients, and early intervention should be conducted for low BMI and weight loss.

Anxiety and depression status in patients with idiopathic pulmonary fibrosis and outcomes of nintedanib treatment: an observational study.

BACKGROUND: Anxiety and depression are common comorbidities in idiopathic pulmonary fibrosis (IPF) that impair health-related quality of life. However, there is a lack of studies focusing on the mental disorder of IPF after antifibrotic treatment and their related predictive factors. METHODS: Patients with an initial diagnosis of IPF were enrolled. Data on demographics, lung function, Generalized Anxiety Disorder-7 (GAD-7) Scale, Patient Health Questionnaire 9 (PHQ-9), Patient Health Questionnaire-15 (PHQ-15), and St. George's Respiratory Questionnaire total score(SGRQ-T) were collected. Changes in anxiety, depression, somatic symptoms, and quality of life scores before and after nintedanib treatment were compared, and the related predictive factors were analyzed. RESULTS: A total of 56 patients with a first diagnosis of IPF were enrolled, with 42 and 35 patients suffering from anxiety and depression, respectively. The GAD-7, PHQ-9, PHQ-15, and SGRQ scores were higher in the anxiety and depression groups. SGRQ total score (SGRQ-T) [OR = 1.075, 95%CI= (1.011, 1.142)] was an independent predictor of IPF combined with anxiety (p < 0.05); SGRQ-T [OR = 1.080, 95%CI= (1.001, 1.167)] was also an independent predictor of IPF combined with depression (p < 0.05). After treatment, GAD-7, PHQ-9, PHQ-15, and SGRQ scores decreased (p < 0.05). ΔSGRQ-T significantly affected ΔGAD-7 (ß = 0.376, p = 0.009) and ΔPHQ-9 (ß = 0.329, p = 0.022). CONCLUSION: Anxiety and depression in IPF patients are closely related to somatic symptoms, pulmonary function, and quality of life. The SGRQ-T score is of great value for assessing anxiety and depression in patients with IPF. Short-term treatment with nintedanib antifibrotic therapy can alleviate anxiety and depression in IPF patients.

Correlation analysis of the peripheral blood lymphocyte count and occurrence of pneumonia after lung transplantation.

BACKGROUND: Infections are the most common complication in patients after lung transplantation and the main cause of death at all stages after transplantation; therefore, awareness regarding the occurrence of infectious pneumonia after lung transplantation is vital. This study aimed to explore the correlation between the absolute lymphocyte and T-lymphocyte subpopulation counts in the peripheral blood and the occurrence of pneumonia after lung transplantation and to predict the risk of pneumonia development after lung transplantation. MATERIALS: Patients who underwent lung transplantation with long-term follow-up between June 2018 and December 2021 were prospectively included. The patients were divided into pneumonia and non-pneumonia groups. Demographic and clinical characteristics, and the levels of leukocytes, neutrophils, platelets, C-reactive protein (CRP), procalcitonin (PCT), serum albumin, peripheral blood T lymphocytes, and CD4+ and CD8+ T cells in the peripheral blood were measured in both groups. RESULTS: We included 22 patients with post-lung transplants in the analysis. Of the 104 collected samples, 26 (56.5%) were pathogenically positive, 16 (61.5%) had bacterial infections, 7 samples (26.9%) had fungal infections, and 8 (30.8%) had viral infections. Patients with pneumonia had higher levels of peripheral blood neutrophils (P = 0.01), platelets (P = 0.03), and CRP (P < 0.001) than did those without pneumonia. Logistic regression analysis showed that the levels of peripheral blood neutrophils, total T lymphocytes, CRP, and PCT were associated with the development of pneumonia after transplantation (P < 0.05), as documented by their area under the curve (AUC) values of 0.702, 0.792, 0.899, and 0.789, respectively. The AUC for the combined receiver operating characteristic curve for predicting the development of pneumonia was 0.943, with a sensitivity of 91.3% and specificity of 93.1%. There was no significant difference in T-lymphocyte counts in patients with lung transplants between the pneumonia and non-pneumonia groups who were treated with two anti-rejection agents. In contrast, the absolute lymphocyte, total T-lymphocyte, and CD4+ and CD8+ T-cell counts in patients who developed pneumonia after treatment with three anti-rejection agents were lower than those in patients who did not develop pneumonia (P < 0.05). CONCLUSION: Bacterial pneumonia is more common after lung transplantation than after fungal or viral infections. Peripheral blood T-lymphocyte counts combined with neutrophil, CRP, and PCT levels had good predictive value for the development of pneumonia after lung transplantation. Monitoring of patients should be strengthened by implementing peripheral blood T-lymphocyte counts to improve the early identification and prevention of pneumonia after lung transplantation.

Draft genome sequencing and annotation of a low-virulence Morganella morganii strain CQ-M7, a multidrug-resistant isolate from the giant salamander in China.

OBJECTIVES: A multidrug-resistant Morganella morganii strain (CQ-M7), isolated from the kidney of a diseased Chinese giant salamander in China, was examined with whole genome sequencing to better understand drug tolerance and its pathogenicity. METHODS: The draft genome of the investigated strain was assembled using HGA assembler and annotated using Rapid Annotations Subsystems Technology (RAST) server. The contigs were annotated by the appropriate bioinformatics tools available on the National Center for Biotechnology Information (NCBI) website. Antibiotic resistance genes were detected by PCR. Pathogenicity of the isolate was performed on 30 healthy Chinese giant salamanders with different infection dosages. RESULTS: The CQ-M7 strain showed resistance to multiple antimicrobials, especially to aminoglycoside and ß-lactam antibiotics. Seventeen drug-resistance genes were detected, which were related to ß-lactams, aminoglycosides, fluoroquinolones, tetracyclines, peptide antibiotic, and fosfomycin resistance. Sequence analysis showed the assembled genome size to be 4 966 326bp with 51.16% of GC content, containing 4587 protein-coding genes, 71 pseudogenes, five rRNAs, 80 tRNAs, and five noncoding RNAs. The genome sequence was deposited in GenBank under accession number RQIJ00000000. Artificial infection results indicated that the CQ-M7 strain was a low-virulence strain for the Chinese giant salamander. CONCLUSION: It is believed that this is the first draft genome of Chinese giant salamander original Morganella morganii strain harbouring multiple antibiotic resistance genes in China. The reported genome sequence could provide insights into antibiotic resistance mechanisms and control strategies of Morganella morganii.

Pneumonia infection by Morganella morganii in a male alpaca.

After sudden death with a history of about two weeks ruminal tympany, a 3-year-old, male alpaca from Huantaiqi Zoo, Chongqing, China was presented to the Animal Diseases Rapid Diagnosis Center, Southwest University, Chongqing, China for diagnosis of the death causes. At necropsy, the primary pathological lesions were found in the lung. A pronounced hemorrhage with topical congestion and lobular pneumonia was identified. Sero-fibrinogenous pleural effusion was also detected in the thoracic cavity. After necropsy, the lung sample was processed for histological examination, while lung, hydropericardium, and heart-blood samples were processed for bacteriological examination. From the lung tissue, abundant fluid exudate was found in the pulmonary alveoli. Meanwhile, a mild to moderate hemorrhage and inflammatory cells infiltrations were also observed in the lung sections. Pure isolates on the 5.00% defibrinated sheep blood agar were submitted for identification by morphological and molecular methods. Sequencing results indicated that the Gram-negative sporadic bacilli were all belonged to Morganella morganii. To the best of our knowledge, this is the first record of M. morganii induced pneumonia in an alpaca.

Diagnosis and characterization of duck beak atrophy and dwarfism syndrome in Chongqing of China.

Duck beak atrophy and dwarfism syndrome (BADS) is a newly emerged disease in China since 2015. In October 2017, an unidentified disease occurred in Cherry Valley ducks, Chongqing municipality, the southwest of China. The affected birds showed short beak and growth retardation clinical signs. The disease caused approximately 20.00% morbidity and serious weight loss due to retarded growth. In order to identify the causative agent of BADS, liver, spleen, lung and heart samples were collected for virus isolation, hemagglutination test, PCR identification, and partial gene sequencing. The isolated virus was tentatively named SC16. Hemagglutination test indicated that the virus was negative to chicken red blood cells. Based on the PCR and sequencing results, the causative agent of BADS was a novel duck-origin goose parvovirus (DGPV) while no another co-infection pathogen was found in this case. Further analysis could provide insights into the control strategies of DGPV in ducks.

Investigation of genetic diversity and epidemiological characteristics of Pasteurella multocida isolates from poultry in southwest China by population structure, multi-locus sequence typing and virulence-associated gene profile analysis.

Fowl cholera caused by Pasteurella multocida has always been a disease of global importance for poultry production. The aim of this study was to obtain more information about the epidemiology of avian P. multocida infection in southwest China and the genetic characteristics of clinical isolates. P. multocida isolates were characterized by biochemical and molecular-biological methods. The distributions of the capsular serogroups, the phenotypic antimicrobial resistance profiles, lipopolysaccharide (LPS) genotyping and the presence of 19 virulence genes were investigated in 45 isolates of P. multocida that were associated with clinical disease in poultry. The genetic diversity of P. multocida strains was performed by 16S rRNA and rpoB gene sequence analysis as well as multilocus sequence typing (MLST). The results showed that most (80.0%) of the P. multocida isolates in this study represented special P. multocida subspecies, and 71.1% of the isolates showed multiple-drug resistance. 45 isolates belonged to capsular types: A (100%) and two LPS genotypes: L1 (95.6%) and L3 (4.4%). MLST revealed two new alleles (pmi77 and gdh57) and one new sequence type (ST342). ST129 types dominated in 45 P. multocida isolates. Isolates belonging to ST129 were with the genes ompH+plpB+ptfA+tonB, whereas ST342 included isolates with fur+hgbA+tonB genes. Population genetic analysis and the MLST results revealed that at least one new ST genotype was present in the avian P. multocida in China. These findings provide novel insights into the epidemiological characteristics of avian P. multocida isolates in southwest China.