Expression and significance of procalcitonin, leukotriene B4, serum amyloid A, and C-reactive protein in children with different types of pneumonia: An observational study.

This study aimed to investigate the expression and significance of serum procalcitonin (PCT), leukotriene B4 (LTB4), Serum amyloid A (SAA), and C-reactive protein (CRP) in children with different types of pneumonia caused by different pathogenic infections. One hundred and one children with pneumonia admitted to The Fifth People Hospital of Zhuhai from July 2019 to June 2020 were enrolled and divided into 38 cases in the bacterial group, 30 cases in the mycoplasma group, and 33 cases in the virus group according to the different types of pathogens. The patients were divided into 42 cases in the noncritical group, 33 cases in the critical group, and 26 cases in the very critical group according to the pediatric clinical illness score (PCIS), and 30 healthy children were selected as the control group during the same period. Comparison of serum PCT, SAA: bacterial group > mycoplasma group > viral group > control group with significant differences (P < .05). Receiver operator characteristic (ROC) analysis showed that the area under the curves (AUCs) of serum PCT, LTB4, SAA, and CRP for the diagnosis of bacterial pneumonia were 1.000, 0.531, 0.969, and 0.833, respectively, and the AUCs for the diagnosis of mycoplasma pneumonia were 0.653, 0.609, 0.547, and 0.652, respectively, and the AUCs for the diagnosis of viral pneumonia were 0.888, 0.570, 0.955, and 1.000, respectively. Comparison of serum PCT, LTB4, SAA: very critical group > critical group > noncritical group > control group, with significant differences (P < .05). Serum PCT, LTB4, and SAA were negatively correlated with PCIS score by Pearson analysis (P < .05). Serum PCT and SAA showed diagnostic value for bacterial pneumonia, and serum SAA and CRP showed diagnostic value for viral pneumonia; serum PCT, LTB4, and SAA correlate with severity of disease and show higher expression with worsening of the condition.

Evaluation of the significance of interleukin-6 in the diagnosis of postoperative pneumonia: a prospective study.

BACKGROUND: Postoperative pneumonia (PP) is one of the most common complications after cardiac surgery. This study was designed to access the diagnostic value of interleukin-6 (IL-6) for pneumonia within the first 5 days after cardiac surgery in adults. METHOD: This prospective observational study enrolled 694 patients who admitted to our center from 10 October 2020 to 30 June 2021. Blood samples were collected after admission and on five consecutive days after surgery to measure IL-6, procalcitonin (PCT), C-reactive protein (CRP) and white blood cells (WBC) respectively. Combined with clinical data, we assessed the diagnostic performance of different biomarkers using univariate and multifactorial analyses as well as receiver operating characteristic curves (ROC) and the area under the curve (AUC). RESULT: Finally, 68 patients were diagnosed with PP (PP Group). In addition, 626 cases were assigned to the control group (Non-PP Group). From postoperative day 1 (POD1) to day 5, IL-6 and PCT levels showed higher diagnostic value (P < 0.001, P < 0.05, respectively); meanwhile, there was no difference in white blood cell counts between the two groups; CRP showed some value from POD2 onwards (P < 0.001). Among these biomarkers, IL-6 on POD1 [AUC: 0.78, 95% confidence interval (CI): 0.71-0.83], IL-6 on POD2 (AUC: 0.77, 95% CI: 0.71-0.82) and CRP levels on POD3 (AUC: 0.77, 95% CI: 0.70-0.84) had the highest diagnostic value. Multivariate analysis found that smoking status [odds ratio(OR): 7.79, 95% CI: 3.05, 19.88, p < 0.001], drinking status (OR: 22.68, 95% CI: 9.29, 55.37, p < 0.001) and hypertension (OR: 2.85, 95% CI: 1.28, 6.35, p = 0.011), IL-6 on POD2 (OR: 1.01, 95% CI: 1.00, 1.01, p = 0.018), mechanical ventilation time (OR: 1.03, 95% CI: 1.00, 1.05, p = 0.040) and intensive care unit stay time (OR: 1.01, 95% CI: 1.00, 1.02, p < 0.001) were independent risk factors for postoperative pneumonia. CONCLUSION: Smoking, drinking, hypertension, prolonged duration of mechanical ventilation and intensive care unit stay, and IL-6 on POD2 were independent risk factors for pneumonia after cardiovascular surgery. IL-6 level on POD2 may serve as a promising indicator, better than WBC, PCT and CRP.

Behavior of clinical and humoral variables on admission as predictors of death in patients with community-acquired pneumonia. Comparative study between adults and older adults. / Comportamiento de variables clínicas y humorales al ingreso, como predictores de fallecimiento en pacientes con neumonía adquirida en la comunidad. Estudio comparativo entre adultos y adultos mayores

Community-acquired pneumonia is recognized as one of the main infectious health problems worldwide. The objective was to determine the condition of predictors of death for a group of selected clinical conditions, and for laboratory variables frequently used in practice. Study with descriptive design, which included 967 patients with pneumonia hospitalized between 2016 and 2019, and whose information was obtained from clinical records. Statistical treatment included bivariate and multivariate analysis (logistic regression); it was used the ratio of crossed products (odds ratio) and its 95% confidence interval. Several manifestations were significantly more frequent in older adults: dyspnea (OR 1.5[1.07,2.1]), absence of productive cough (OR 1.7 [1.3, 2.4]), neuropsychological manifestations (OR 2 [1.4,2.8]), tachypnea (OR 1.5 [1.1,2.1]), arterial hypotension (OR 2.1 [1.2,3.6]), anemia (OR 1.6[1.2,2.2]), elevated creatinine (OR 1.6[1.2,2.3]) and hypoproteinemia (OR 3.3[1.9,5.7]); showed a significant association with death: absence of productive cough, neuropsychological manifestations, temperature below 36 degrees Celsius, blood pressure below 110/70 mmHg, respiratory rate above 20 per minute, hemoglobin below 100 g/L, erythrosedimentation greater than 20 mm/L, leukopenia less than 5 x 109/L and serum creatinine above 130 micromol/L. As conclusions certain clinical and laboratory conditions present in the patient at the time of hospital admission, of routine exploration in the comprehensive assessment of the patient, were predictors of death. Additionally, the existence of evident differences in the number of conditions with a predictive nature of death between the population with pneumonia under 60 years of age and the elderly, as well as in the frequency of these conditions in both subgroups, is verified.

La neumonía adquirida en la comunidad está reconocida como uno de los principales problemas de salud de tipo infeccioso al nivel mundial. La investigación tuvo como objetivo determinar el carácter de predictores de fallecimiento de un grupo de condiciones clínicas seleccionadas, y de variables de laboratorio de uso frecuente en la práctica. Se realizó un estudio con diseño descriptivo, que incluyó a 967 pacientes con neumonía hospitalizados entre 2016 y 2019, y cuya información se obtuvo de los expedientes clínicos. El tratamiento estadístico incluyó análisis bivariante y multivariado (regresión logística); como estadígrafo se utilizó la razón de productos cruzados (odds ratio) y su intervalo de confianza de 95%. Entre los resultados se destacan los siguientes: varias manifestaciones fueron significativamente más frecuentes en los adultos mayores: disnea (OR 1,5[1,07;2,1]), ausencia de tos productiva (OR 1,7[1,3;2,4]), manifestaciones neuropsicológicas (OR 2[1,4;2,8]), taquipnea (OR 1,5[1,1;2,1]), hipotensión arterial (OR 2,1[1,2;3,6]), anemia (OR 1,6[1,2;2,2]), creatinina elevada (OR 1,6[1,2;2,3]) e hipoproteinemia (OR 3,3[1,9;5,7]); mostraron asociación significativa con el fallecimiento: ausencia de tos productiva, manifestaciones neuropsicológicas, temperatura por debajo de 36 grados Celsius, tensión arterial inferior a 110/70 mmHg, frecuencia respiratoria por encima de 20 por minuto, hemoglobina inferior a 100 g/L, velocidad de sedimentación eritrocitaria superior a 20 mm/L, leucopenia inferior a 5 x 109/L y creatinina sérica por encima de 130 micromol/L. Se concluye que ciertas condiciones clínicas y de laboratorio presentes en el paciente al momento del ingreso hospitalario, de exploración habitual en la valoración integral del enfermo, constituyeron predictores de fallecimiento. Adicionalmente, se comprueba la existencia de evidentes diferencias en el número de condiciones con carácter predictor de muerte entre la población con neumonía menor de 60 años y los adultos mayores, así como en la frecuencia de estas condiciones en ambos subgrupos.

Functional Ex Vivo Testing of Alveolar Monocytes in Patients with Pneumonia-Related ARDS.

Biomarkers of disease severity might help with individualizing the management of patients with acute respiratory distress syndrome (ARDS). During sepsis, a sustained decreased expression of the antigen-presenting molecule human leucocyte antigen-DR (HLA-DR) on circulating monocytes is used as a surrogate marker of immune failure. This study aimed at assessing whether HLA-DR expression on alveolar monocytes in the setting of a severe lung infection is associated with their functional alterations. BAL fluid and blood from immunocompetent patients with pneumonia-related ARDS admitted between 2016 and 2018 were isolated in a prospective monocentric study. Alveolar and blood monocytes were immunophenotyped using flow cytometry. Functional tests were performed on alveolar and blood monocytes after in vitro lipopolysaccharide (LPS) stimulation. Phagocytosis activity and intracellular tumor necrosis factor (TNF) production were quantified using fluorochrome-conjugated-specific antibodies. Ten ARDS and seven non-ARDS control patients were included. Patients with pneumonia-related ARDS exhibited significantly lower HLA-DR expression both on circulating (p < 0.0001) and alveolar (p = 0.0002) monocytes. There was no statistically significant difference observed between patient groups (ARDS vs. non-ARDS) regarding both alveolar and blood monocytes phagocytosis activity. After LPS stimulation, alveolar (p = 0.027) and blood (p = 0.005) monocytes from pneumonia-related ARDS patients had a significantly lower intracellular TNF expression than non-ARDS patients. Monocytes from pneumonia-related ARDS patients have a deactivated status and an impaired TNF production capacity but display potent phagocytic activity. HLA-DR level expression should not be used as a surrogate marker of the phagocytic activity or the TNF production capacity of alveolar monocytes.

Salivary Interleukin-6 and C-Reactive Protein/Mean Platelet Volume Ratio in the Diagnosis of Late-Onset Neonatal Pneumonia.

Neonatal pneumonia is a serious respiratory infectious disease with a high rate of case fatality in developing countries. Salivary cytokines could serve as interesting noninvasive markers in the diagnosis of neonatal pneumonia. The aim was to assess the diagnostic role of salivary and serum interleukin-6 (IL-6), C-reactive protein/mean platelet volume (CRP/MPV) ratio, and the combination of these markers in the diagnosis of late-onset neonatal pneumonia in full-term neonates. Seventy full-term neonates, 35 with late-onset neonatal pneumonia and 35 controls, were enrolled in this prospective case-control study. Complete blood count (CBC), salivary and serum IL-6, and CRP concentrations were measured for all the study subjects. The sensitivity, specificity, positive predictive value, and negative predictive value of salivary IL-6, serum IL-6, and CRP/MPV ratio for the diagnosis of late-onset neonatal pneumonia were determined. At the cutoff point of >34 pg/ml, salivary IL-6 showed 82.86% sensitivity and 91.43% specificity. CRP/MPV ratio showed a sensitivity of 97.14% and specificity of 85.71% at a cutoff value > 0.88. The combination of salivary IL-6 and CRP/MPV ratio improved the sensitivity and specificity to 100%. The current study shows for the first time that both salivary IL-6 and CRP/MPV ratio are suitable markers for the diagnosis of late-onset neonatal pneumonia in full-term neonates.

Mesenchymal Stem Cells in the Treatment of COVID-19, a Promising Future.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells' differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration. MSCs are considered safe for human treatment; their use does not involve ethical issues, as embryonic stem cells do not require genetic manipulation as induced pluripotent stem cells, and after intravenous injection, they are mainly found in the lugs. Therefore, these cells are currently being tested in various preclinical and clinical trials for several diseases, including COVID-19. Several affected COVID-19 patients develop induced acute respiratory distress syndrome (ARDS) associated with an uncontrolled inflammatory response. This condition causes extensive damage to the lungs and may leave serious post-COVID-19 sequelae. As the disease may cause systemic alterations, such as thromboembolism and compromised renal and cardiac function, the intravenous injection of MSCs may be a therapeutic alternative against multiple pathological manifestations. In this work, we reviewed the literature about MSCs biology, focusing on their function in pulmonary regeneration and their use in COVID-19 treatment.

The Role of Red Blood Cell Distribution Width in the Severity and Prognosis of Community-Acquired Pneumonia.

Objectives: The objective of this study is to unravel the correlation between RDW and the severity and prognosis of CAP, as well as exploring RDW with the inflammatory markers white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT). Methods: According to the data characteristics, appropriate statistical methods were selected to analyze the relationship between RDW and the severity and prognosis of CAP patients and to determine whether RDW is associated with the inflammatory markers WBC, CRP, and PCT. Results: The results show that with the increase of PSI and CURB-65 values, the proportion of patients with RDW ≥ 12.987% is significantly higher than that of RDW < 12.987% (P < 0.01). When RDW is combined with PSI or CURB-65 to predict the 90-day mortality of CAP patients, the area under the receiver operating characteristic (ROC) curve increased prominently, and if RDW, PSI, and CURB-65 are combined, the area under the ROC curve is maximized. Conclusions: Our findings suggest that the higher RDW value is associated with short-term adverse outcomes in CAP patients. We also find that when RDW, PSI, and CURB-65 are combined, the best performance is achieved to predict CAP 90-day mortality risk.

False-positive HIV serology, Candida lusitaniae pneumonia, and a novel mutation in the CYBB gene.

BACKGROUND: Chronic granulomatous disease (CGD) presents with a myriad of clinical manifestations pertaining to both immunodeficiency and hyperinflammation. Although Candida infection is a signature organism for patients with CGD, C. lusitaniae pneumonia in CGD has rarely been reported. C. lusitaniae is a ubiquitous ascomycete predominantly infecting immunocompromised hosts and has the potential to rapidly develop multi-drug resistance during therapy. Additionally, C. lusitaniae is recognized for its variable resistance against amphotericin B. To date, C. lusitaniae infections in patients with CGD have not been reviewed in detail. False-positive HIV serology, resulting from polyclonal hypergammaglobulinemia, has been reported in association with several infections, auto-immune diseases, and malignancies. Although CGD is often associated with hypergammaglobulinemia, a false-positive HIV serology in CGD has not been reported previously. PROCEDURE: We report a combination of unique findings in a child with CGD - a false-positive HIV serology, Candida lusitaniae pneumonia, and a novel CYBB mutation. We also provide a detailed review of C. lusitaniae infections in patients with CGD. RESULTS: In patients with CGD, C. lusitaniae has been reported to cause lymphadenitis (cervical, abdominal), fungemia, meningoencephalitis, or abscesses in the liver and spleen. Many CGD patients with C. lusitaniae infection have associated inflammatory complications of the gut (inflammatory bowel disease, colitis). Additionally, almost all C. lusitaniae infections in CGD have been reported in young infants or in patients receiving long-term immunosuppressive therapy. This reflects that further immunocompromise (in addition to the underlying immune deficiency in CGD) may specifically predispose to C. lusitaniae infection (unlike other candidal infections). Most of the CGD patients with documented C. lusitaniae infection have X-linked form of the disease which generally has been postulated to have a more severe clinical phenotype than the autosomal recessive forms of the disease. CONCLUSIONS: HIV serology may be positive in patients with CGD and other inborn errors of immunity as a result of hypergammaglobulinemia. C. lusitaniae, which may have peculiar and evolving antimicrobial sensitivity patterns, needs to be considered in patients with CGD and pneumonia. Lastly, to reiterate, CGD should to be considered in patients with proven C. lusitaniae infection.

Effects of dexmedetomidine combined with citrate sufentanil on the prognosis of patients with severe pneumonia and respiratory failure requiring mechanical ventilation.

To investigate the effects of dexmedetomidine combined with citrate sufentanil on the prognosis of patients with severe pneumonia and respiratory failure requiring mechanical ventilation. 70 patients with severe pneumonia complicated with respiratory failure who were treated with mechanical ventilation were selected and divided into the combined group and the control group. The control group underwent mechanical ventilation treatment and used dexmedetomidine for sedation and analgesia, while the combined group had sufentanil analgesia in addition to the treatment of the control group. Ramsay sedation score, visual analogue scale (VAS) and pulmonary function indicators were compared between the two groups before treatment, 24h after treatment, and after extubation. After 24h treatment and extubation, the blood oxygen saturation (SpO2), oxygenation index (OI) and arterial oxygen partial pressure (PaO2) in the combined group were higher than those in the control group; at the same time, the serum interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and malondialdehyde (MDA) levels were lower (P<0.05). Mortality during hospitalization of the combined group was lower than the control group (P<0.05). Dexmedetomidine combined with sufentanil citrate can effectively improve sedative and analgesic effects, stress response, pulmonary function and prognosis in patients with severe respiratory failure requiring mechanical ventilation.

Sex-specific differences in plasma levels of FXII, HK, and FXIIa-C1-esterase inhibitor complexes in community-acquired pneumonia.

Sex-dependent differences in immunity and coagulation play an active role in the outcome of community-acquired pneumonia (CAP). Contact phase proteins act at the crossroads between inflammation and coagulation thus representing a point of convergence in host defense against infection. Here, we measured the levels of factor XII (FXII), FXIIa-C1 esterase inhibitor (C1INH) complexes, and high-molecular-weight kininogen (HK) in plasma of patients with CAP and correlated them to clinical disease severity. Levels of FXIIa-C1INH/albumin ratio were elevated, irrespective of sex, in plasma of patients with CAP (n = 139) as compared with age-matched donors (n = 58). No simultaneous decrease in FXII levels, indicating its consumption, was observed. Stratification by sex revealed augmented FXII levels in plasma of women with CAP as compared with sex-matched donors yet no apparent differences in men. This sex-specific effect was, however, attributable to lower FXII levels in female donors relative to men donors. Plasma estradiol levels mirrored those for FXII. Levels of HK/albumin ratio were decreased in CAP plasma as compared with donors, however, after stratification by sex, this difference was only observed in women and was related to higher HK/albumin values in female donors as opposed to male donors. Finally, strong negative correlation between plasma levels of HK/albumin ratio and CAP severity, as assessed by CRB65 score, in males and females was observed. Our study identifies sex-dependent differences in plasma levels of the contact phase proteins in elderly subjects that may contribute to specific clinical outcomes in CAP between men and women.

Serum MCP-1 and NGAL Play an Important Role in the Acute Inflammatory Event of Chronic Obstructive Pulmonary Disease.

NGAL is mainly secreted by neutrophils which play the core role in AECOPD. MCP-1 is secreted specifically by monocytes and macrophages. Both biomarkers are involved in the core process of acute inflammatory reaction in COPD. So We analyzed serum NGAL and MCP-1levels to explore their potential clinical values in the chronic obstructive pulmonary disease (COPD) .This study enrolled 97 COPD patients and 50 healthy controls. All participants received blood collection and lung function test and arterial blood gas measurements. The expression levels of serum NGAL and MCP-1 were measured by ELISA. The serum NGAL and MCP-1 levels of COPD with community-acquired pneumonia (COPD-CAP) patients were significantly higher than those of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients and healthy adults. The NGAL levels of the GOLD III and IV groups were significantly higher than those of the GOLD II group. Spearman correlation analysis showed a negative correlation between NGAL and FEV1%pred, FVC% pred. ROC curves indicated that NGAL has a high diagnostic value for both AECOPD and COPD-CAP. NGAL has the value of distinguishing GOLD I and II from GOLD III and IV. MCP-1 have moderate diagnostic value for COPD-CAP and can differentiate COPD-CAP from AECOPD. This study shows NGAL has certain diagnostic value for AECOPD and COPD-CAP, but can not distinguish the two. NGAL is closely related to airway remodeling and can be used as a potential indicator to distinguish the higher GOLD degree. MCP-1 can be used as potential indicator for the diagnosis of COPD-CAP.

Analysis of Lymphocyte Subpopulations and Cytokines in COVID-19-Associated Pneumonia and Community-Acquired Pneumonia.

BACKGROUND: The 2019 novel coronavirus SARS-CoV-2 caused large outbreaks of COVID-19 worldwide. COVID-19 resembles community-acquired pneumonia (CAP). Our aim was to identify lymphocyte subpopulations to distinguish between COVID-19 and CAP. METHODS: We compared the peripheral blood lymphocytes and their subsets in 296 patients with COVID-19 and 130 patients with CAP. Parameters for independent prediction of COVID-19 were calculated by logistic regression. RESULTS: The main lymphocyte subpopulations (CD3+CD4+, CD16+CD56+, and CD4+/CD8+ ratio) and cytokines (TNF-α and IFN-γ) of COVID-19 patients were significantly different from that of CAP patients. CD16+CD56+%, CD4+/CD8+ratio, CD19+, and CD3+CD4+ were identified as predictors of COVID-19 diagnosis by logistic regression. In addition, the CD3+CD4+counts, CD3+CD8+ counts, andTNF-α are independent predictors of disease severity in patients. CONCLUSIONS: Lymphopenia is an important part of SARS-CoV-2 infection, and lymphocyte subsets and cytokines may be useful to predict the severity and clinical outcomes of the disease.

Dosing Optimization of Ampicillin-Sulbactam Based on Cystatin C in Elderly Patients with Pneumonia.

Ampicillin-sulbactam is a first-line therapy for pneumonia and is mainly excreted by the kidney. It is important to optimize the dose and dosing interval of ampicillin-sulbactam because in patients with decreased renal function and low skeletal muscle mass, such as the elderly, excess drug may burden renal function. In this study, we evaluated indices of renal function and optimized the dose and dosing interval of ampicillin-sulbactam based on pharmacokinetics (PK) and pharmacodynamics theory in elderly patients. The serum concentrations of ampicillin and sulbactam were measured by HPLC, and PK parameters were calculated. Correlations between the clearance of ampicillin or sulbactam and renal function were evaluated, and dosing optimization was calculated based on PK parameters. The PK parameters of ampicillin were CL = 6.5 ± 4.0 L/h, Vd = 19.3 ± 0.2 L, Ke = 0.4 ± 0.2, and t1/2 = 2.7 ± 1.6 h. The most correlated renal function index was estimated glomerular filtration rate (eGFRcys-c) calculated by serum cystatin-c (r = 0.7374, correlation formula; CL of ampicillin = 0.1937 × eGFRcys-c-0.6726). Based on this formula, we calculated the clearance of ampicillin and developed dosing regimens for the elderly. Serum cystatin-c concentration is an ideal index to optimize ampicillin-sulbactam antimicrobial therapy in elderly patients with pneumonia.

Influence of Prednisone on Inflammatory Biomarkers in Community-Acquired Pneumonia: Secondary Analysis of a Randomized Trial.

Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID-19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous multicenter, randomized, placebo-controlled trial that compared a 7-day treatment course of 50-mg prednisone to placebo in patients hospitalized with community-acquired pneumonia. We compared levels of C-reactive protein (CRP), procalcitonin (PCT), leukocyte and neutrophil count between patients with and without glucocorticoid treatment at baseline and on days 3, 5, and 7 and at discharge by Wilcoxon tests and analysis of variance. A total of 356 patient data sets in the prednisone group and 355 in the placebo group were available for analysis. Compared to placebo, use of prednisone was associated with reductions in levels of CRP on days 3, 5, and 7 (mean difference of 46%, P < .001 for each time point). For PCT, no such difference was observed. Leukocyte and neutrophil count were higher in the prednisone group at all time points (mean difference of 27% for leukocytes and 33% for neutrophils, P <.001 for all time points). We conclude that after administration of glucocorticoids in community-acquired pneumonia, patients had lower CRP levels and increased leukocyte and neutrophil count as compared to the placebo group. PCT levels were not different between treatment groups. PCT levels thus may more appropriately mirror the resolution of infection compared to more traditional inflammatory markers.

Knockdown of circ-UQCRC2 ameliorated lipopolysaccharide-induced injury in MRC-5 cells by the miR-326/PDCD4/NF-κB pathway.

BACKGROUND: Circular RNAs (circRNAs) have been shown as important modulators in the pathogenesis of pediatric pneumonia. In this paper, we focused on the molecular basis of circRNA ubiquinol-cytochrome c reductase core protein 2 (circ-UQCRC2, circ_0038467) in lipopolysaccharide (LPS)-induced cell injury. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to gauge the levels of circ-UQCRC2, microRNA (miR)-326 and programmed cell death 4 (PDCD4) mRNA. PDCD4 protein expression and the activation of the NF-κB signaling pathway were evaluated by western blot. Ribonuclease R (RNase R) assay was performed to assess the stability of circ-UQCRC2. Cell viability and apoptosis were detected by the Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 were measured by the enzyme-linked immunosorbent assay (ELISA). Targeted relationship between miR-326 and circ-UQCRC2 or PDCD4 was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: Our data showed the up-regulation of circ-UQCRC2 level in pneumonia serum and LPS-treated MRC-5 cells. The silencing of circ-UQCRC2 attenuated LPS-induced MRC-5 cell injury. Mechanistically, circ-UQCRC2 directly targeted miR-326, and circ-UQCRC2 regulated PDCD4 expression through miR-326. MiR-326 was a downstream effector of circ-UQCRC2 function, and PDCD4 was a functional target of miR-326 in regulating LPS-induced MRC-5 cell injury. Additionally, circ-UQCRC2 knockdown inactivated the NF-κB signaling pathway by regulating the miR-326/PDCD4 axis. CONCLUSION: Our findings demonstrated a novel regulatory network, the miR-326/PDCD4/NF-κB pathway, for the function of circ-UQCRC2 in LPS-induced cell injury in MRC-5 cells.

An L-Shaped Relationship Between Serum Iron and Stroke-Associated Pneumonia.

OBJECTIVE: Pneumonia is a common complication in patients with stroke. There was a close relationship between serum iron and inflammatory response. This study aimed to explore the relationship between serum iron levels and stroke-associated pneumonia (SAP). METHODS: Patients with acute stroke were recruited from the First Affiliated Hospital of Wenzhou Medical University and divided into SAP group and Non-SAP group. The demographic and clinical data of the patients were collected via the medical records, and the blood samples were collected within 24 hours after admission. The predictive value of serum iron to SAP was evaluated by receiver operating characteristic curve (ROC) and binary Logistic regression models. A restricted cubic spline (RCS) was used to furtherly clarify the relationship between serum iron and the risk of SAP. RESULTS: A total of 906 participants were enrolled, including Non-SAP group (n = 755) and SAP group (n = 151). Serum iron levels in the SAP group were significantly lower than those in the Non-SAP group (9.77±5.61 vs 14.01±6.80, P < 0.001). Logistic regression showed that patients with high serum iron levels (≥7.8µmol/L) showed a lower risk of SAP (OR=0.43, 95% CI, 0.27-0.69, P < 0.001). Besides, the RCS model showed that there was an L-shaped relationship between the serum iron and risk of SAP (P for non-linearity: 0.014). CONCLUSION: Low serum iron level was a risk factor for SAP, and there was an L-shaped relationship between them. Stroke patients with low serum iron levels should be alert to the risk of SAP.

Pulmonary Follow-Up Imaging in Cartilage-Hair Hypoplasia: a Prospective Cohort Study.

Cartilage-hair hypoplasia is a syndromic immunodeficiency with short stature, chondrodysplasia, and variable degree of immune dysfunction. Patients with cartilage-hair hypoplasia are prone to recurrent respiratory tract infections, and the prevalence of bronchiectasis ranges from 29 to 52%. Pulmonary complications contribute significantly to the mortality; therefore, regular lung imaging is essential. However, the optimal schedule for repeated lung imaging remains unestablished. We determined the rate and correlates of progression of structural lung changes in a prospectively followed cohort of 16 patients with cartilage-hair hypoplasia. We analyzed clinical, laboratory, and pulmonary functional testing data and performed lung magnetic resonance imaging at a median interval of 6.8 years since previous imaging. Imaging findings remained identical or improved due to disappearance of inflammatory changes in all evaluated patients. Patients with subtle signs of bronchiectasis on imaging tended to have low immunoglobulin M levels, as well as suffered from pneumonia during the follow-up. In conclusion, our results suggest slow if any development of bronchiectasis in selected subjects with cartilage-hair hypoplasia.

Establishing Classifiers With Clinical Laboratory Indicators to Distinguish COVID-19 From Community-Acquired Pneumonia: Retrospective Cohort Study.

BACKGROUND: The initial symptoms of patients with COVID-19 are very much like those of patients with community-acquired pneumonia (CAP); it is difficult to distinguish COVID-19 from CAP with clinical symptoms and imaging examination. OBJECTIVE: The objective of our study was to construct an effective model for the early identification of COVID-19 that would also distinguish it from CAP. METHODS: The clinical laboratory indicators (CLIs) of 61 COVID-19 patients and 60 CAP patients were analyzed retrospectively. Random combinations of various CLIs (ie, CLI combinations) were utilized to establish COVID-19 versus CAP classifiers with machine learning algorithms, including random forest classifier (RFC), logistic regression classifier, and gradient boosting classifier (GBC). The performance of the classifiers was assessed by calculating the area under the receiver operating characteristic curve (AUROC) and recall rate in COVID-19 prediction using the test data set. RESULTS: The classifiers that were constructed with three algorithms from 43 CLI combinations showed high performance (recall rate >0.9 and AUROC >0.85) in COVID-19 prediction for the test data set. Among the high-performance classifiers, several CLIs showed a high usage rate; these included procalcitonin (PCT), mean corpuscular hemoglobin concentration (MCHC), uric acid, albumin, albumin to globulin ratio (AGR), neutrophil count, red blood cell (RBC) count, monocyte count, basophil count, and white blood cell (WBC) count. They also had high feature importance except for basophil count. The feature combination (FC) of PCT, AGR, uric acid, WBC count, neutrophil count, basophil count, RBC count, and MCHC was the representative one among the nine FCs used to construct the classifiers with an AUROC equal to 1.0 when using the RFC or GBC algorithms. Replacing any CLI in these FCs would lead to a significant reduction in the performance of the classifiers that were built with them. CONCLUSIONS: The classifiers constructed with only a few specific CLIs could efficiently distinguish COVID-19 from CAP, which could help clinicians perform early isolation and centralized management of COVID-19 patients.

AT-RvD1 Mitigates Secondhand Smoke-Exacerbated Pulmonary Inflammation and Restores Secondhand Smoke-Suppressed Antibacterial Immunity.

Cigarette smoke is a potent proinflammatory trigger contributing to acute lung injury and the development of chronic lung diseases via mechanisms that include the impairment of inflammation resolution. We have previously demonstrated that secondhand smoke (SHS) exposure exacerbates bacterial infection-induced pulmonary inflammation and suppresses immune responses. It is now recognized that resolution of inflammation is a bioactive process mediated by lipid-derived specialized proresolving mediators that counterregulate proinflammatory signaling and promote resolution pathways. We therefore hypothesized that proresolving mediators could reduce the burden of inflammation due to chronic lung infection following SHS exposure and restore normal immune responses to respiratory pathogens. To address this question, we exposed mice to SHS followed by chronic infection with nontypeable Haemophilus influenzae (NTHI). Some groups of mice were treated with aspirin-triggered resolvin D1 (AT-RvD1) during the latter half of the smoke exposure period or during a period of smoking cessation and before infection. Treatment with AT-RvD1 markedly reduced the recruitment of neutrophils, macrophages, and T cells in lung tissue and bronchoalveolar lavage and levels of proinflammatory cytokines in the bronchoalveolar lavage. Additionally, treatment with AT-RvD1 improved Ab titers against the NTHI outer membrane lipoprotein Ag P6 following infection. Furthermore, treatment with AT-RvD1 prior to classically adjuvanted immunization with P6 increased Ag-specific Ab titers, resulting in rapid clearance of NTHI from the lungs after acute challenge. Collectively, we have demonstrated that AT-RvD1 potently reverses the detrimental effects of SHS on pulmonary inflammation and immunity and thus could be beneficial in reducing lung injury associated with smoke exposure and infection.