[Diagnostic yield of bronchoscopic rapid on-site evaluation in severe invasive bronchopulmonary aspergillosis].

OBJECTIVE: To explore the diagnostic yield of bronchoscopic rapid on-site evaluation (B-ROSE) in patients with severe invasive bronchopulmonary aspergillosis (IBPA) and provide evidence for starting antifungal treatment before microbiological results were available. METHODS: A prospective cohort study was conducted to select patients with severe pneumonia suspected of IBPA admitted to the respiratory intensive care unit (RICU) in the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2022, and those who were primarily infected with other pathogens (such as bacteria, Mycobacterium tuberculosis) at admission were excluded. Whether the antifungal treatment was initiated or not on the basis of the bedside B-ROSE, the B-ROSE was administered as soon as possible within 24 hours after admission to RICU. The current international definition of invasive aspergillosis was used as the gold diagnostic standard, the diagnostic accordance rate, the sensitivity and specificity of B-ROSE were calculated respectively, and the receiver operator characteristic curve (ROC curve) was also plotted, to evaluate the predictive value in diagnosing IBPA. RESULTS: A total of 176 patients with severe pneumonia suspected of IBPA were included in the study. According to international diagnostic standards, there were 81 cases of IBPA and 95 cases of non-IBPA. According to the early diagnosis of B-ROSE, there were 89 cases of IBPA and 87 cases of non-IBPA. The diagnostic accordance rate of B-ROSE was 84.09% (148/176), the area under the ROC curve for B-ROSE in diagnosing severe IBPA was 0.844, the 95% confidence interval (95%CI) was 0.782-0.905, the sensitivity was 87.65%, the specificity was 81.05%, the positive predictive value was 79.78%, the negative predictive value was 88.51%, the rate of underdiagnosis was 12.35% (10/81), and the rate of misdiagnosis was 18.95% (18/95). Compared with the true negative group, the proportion of long-term (≥ 14 days) use of glucocorticoid [70.0% (7/10) vs. 9.1% (7/77), P < 0.01] and the proportion of cases with diabetes [40.0% (4/10) vs. 10.4% (8/77), P < 0.05] were significantly higher in the false negative group (underdiagnosis group). However, B-ROSE of both groups showed mucosal bleeding, congestion and edema [100.0% (10/10) vs. 94.8% (73/77), P > 0.05], indicating that acute mucosal inflammation was non-characteristic. Compared with the true positive group, the proportion of long-term (≥ 14 days) use of glucocorticoid in the false positive group (misdiagnosis group) was significantly reduced [33.3% (6/18) vs. 60.6% (43/71), P < 0.05]. The B-ROSE results showed the proportion of cases with mucosal white spots, black plaques and pseudomembrane was significantly reduced [16.7% (3/18) vs. 52.1% (37/71), P < 0.01] in the misdiagnosed group, which suggest that cases of long-term use of glucocorticoid and cases with B-ROSE showing mucosal white spots, black plaques and pseudomembrane were less likely to be misdiagnosed. The main diseases that were easily misdiagnosed as IBPA included pulmonary tuberculosis (38.9%, 7/18), inflammatory lung adenocarcinoma (27.8%, 5/18) and pulmonary vasculitis (16.7%, 3/18). CONCLUSIONS: Before obtaining microbiological evidence, B-ROSE can assist in decision-making of early anti-aspergillus treatment for severe IBPA. This method is prompt, simple, and has high accuracy and reliability. If B-ROSE lacks characteristic manifestations, especially for severe pneumonia in patients with long-term use of glucocorticoid or diabetes, attention should be paid to the underdiagnosis of IBPA. Diseases such as lung tuberculosis, inflammatory lung adenocarcinoma and lung vasculitis should be vigilant against misdiagnosis as IBPA.

[Rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by diagnostic bronchoscopy].

OBJECTIVE: To explore the rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by bedside diagnostic bronchoscopy, so as to start effective anti-infection treatment before the results of macrogenome next generation sequencing (mNGS) test. METHODS: The clinical data of three patients with severe Chlamydophila psittaci pneumonia who were successfully treated in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Aksu District, and the First Division Hospital of Xinjiang Production and Construction Corps from October 2020 to June 2021 were retrospectively analyzed, including the rapid assessment of early pathogens by bedside diagnostic bronchoscopy and the use of antibiotics to start anti-infection treatment. These patients were successfully treated. RESULTS: The three patients were male, aged 63, 45 and 58 years old, respectively. Before the onset of the penumonia, they had a clear medical history of bird exposure. The clinical manifestations mainly included fever, dry cough, shortness of breath and dyspnea. One case had abdominal pain and lethargy. The results of laboratory examination indicated that the peripheral blood white blood cell count (WBC) of two patients were high [(10.2-11.9)×109/L], the percentage of neutrophils increased (85.2%-94.6%) and the percentage of lymphocytes decreased (3.2%-7.7%) in all 3 patients after admission to hospital and entering into intensive care unit (ICU). The procalcitonin (PCT) of 3 patients increased after admission, and still increased when entering ICU (0.3-4.8 ng/L), so did C-reactive protein (CRP, 58.0-162.0 mg/L) and erythrocyte sedimentation rate (ESR, 36.0-90.0 mm/1 h). After admission, serum alanine transaminase (ALT) increased in 2 cases (136.7 U/L, 220.5 U/L), so did aspartate transaminase (AST) in 2 cases (249.6 U/L, 164.2 U/L). ALT (162.2-267.9 U/L) and AST (189.8-223.2 U/L) increased in 3 patients when they entered ICU. The level of serum creatinine (SCr) of 3 patients were normal after admission and entering ICU. The chest computed tomography (CT) findings of 3 patients were acute interstitial pneumonia, bronchopneumonia and lung consolidation, of which 2 cases were accompanied by a small amount of pleural effusion, and 1 case was accompanied by more regular small air sacs. Multiple lung lobes were involved, but mainly one lung lobe. The oxygenation index (PaO2/FiO2) of the 3 patients admitting to ICU were 100.0, 57.5 and 105.4 mmHg (1 mmHg ≈ 0.133 kPa), respectively, which met with the diagnostic criteria of moderate and severe acute respiratory distress syndrome (ARDS). All three patients received endotracheal intubation and mechanical ventilation. Under the bedside bronchoscope, the bronchial mucosa of 3 patients were obviously congested and edematous, without purulent secretion, and there was 1 case with mucosal hemorrhage. Three patients underwent bedside diagnostic bronchoscopy, and the evaluation result of the pathogen was that it might be atypical pathogen infection, so they were given moxifloxacin, cisromet and doxycycline intravenously, respectively, and combined with carbapenem antibiotics intravenously. After 3 days, the detection results of mNGS in bronchoalveolar lavage fluid (BALF) showed that only Chlamydia psittaci was infected. At this time, the condition was significantly improved, and PaO2/FiO2 was significantly increased. Therefore, the antibiotic treatment scheme remained unchanged, and mNGS only served to verify the initial diagnosis. Two patients were extubated on the 7th and 12th day of admission to the ICU, respectively, while one patient was extubated on the 16th day of admission to the ICU due to nosocomial infection. All 3 patients were transferred to the respiratory ward after the condition was stable. CONCLUSIONS: The bedside diagnostic bronchoscopy based on clinical characteristics is conducive to not only the rapid assessment of the early pathogens of severe Chlamydia psittaci pneumonia, but also effective anti-infection treatment before the returning of mNGS test results, which can make up for the lag and uncertainty of the mNGS test results.

[Factors influencing the choice of endotracheal intubation and mechanical ventilation in patients with acute respiratory distress syndrome caused by viral pneumonia].

OBJECTIVE: To investigate the influencing factors of endotracheal intubation and mechanical ventilation (ETI-MV) in patients with acute respiratory distress syndrome (ARDS) caused by viral pneumonia, and to provide evidence for individualized use of ETI-MV. METHODS: Patients with ARDS due to viral pneumonia admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed from November 2017 to March 2022. The gender, age, concomitant diseases, clinical symptoms and signs, complications, lab results, ARDS severity, infectious virus type, acute physiology and chronic health evaluation II (APACHE II), respiratory support methods and prognosis-related variables were collected. Univariate analysis was performed on each factor, and the variables with statistical significance in the univariate analysis were subjected multivariate logistic regression analysis. The receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of each index for the implementation of ETI-MV. RESULTS: A total of 117 patients were enrolled in the study, including 61 patients in the ETI-MV group, and 3 patients (4.9%), 39 patients (63.9%) and 19 patients (31.1%) with mild, moderate and severe ARDS, respectively. There were 56 patients in non-ETI-MV group, and the mild, moderate and severe ARDS cases were 16 cases (28.6%), 38 cases (67.8%) and 2 cases (3.6%), respectively. There was significant difference between the two groups (P < 0.05). Univariate analysis showed that during 24 hours admitted to RICU, the levels of interleukin-6 [IL-6 (ng/L): 104.0±90.0 vs. 62.4±76.0], oxygenation index [PaO2/FiO2 (mmHg, 1 mmHg ≈ 0.133 kPa): 123.9±30.9 vs. 173.6±28.5], the proportion of cases with pulmonary infiltrating opacity distribution range ≥ 3/4 lung fields [85.3% (52/61) vs. 21.5% (12/56)], APACHE II score ≥ 16.5 [67.2% (41/61) vs. 42.9% (24/56)], the rate of nosocomial invasive aspergillus infection [14.8% (9/61) vs. 3.6% (2/56)], the percentage of nosocomial bacterial infection [16.4% (10/61) vs. 3.6% (2/56)], and the lowest CD4+ T lymphocyte count in the course of the disease [cells/mm3: 192.2±35.8 vs. 215.0±58.3] had significant differences between ETI-MV and non-ETI-MV group (all P < 0.05). Multivariate Logistic regression analysis showed that during 24 hours admitted to RICU the distribution range of pulmonary infiltrating opacity ≥ 3/4 the lung fields [odds ratio (OR) = 12.527, 95% confidence interval (95%CI) = 3.279-47.859, P < 0.001], APACHE II score ≥ 16.5 (OR = 30.604, 95%CI = 4.318-216.932, P = 0.001), PaO2/FiO2 (OR = 0.948, 95%CI = 0.925-0.972, P < 0.001), CD4+ T lymphocytes cell count (OR = 0.975, 95%CI = 0.955-0.995, P = 0.015), and nosocomial bacterial infection (OR = 38.338, 95%CI = 1.638-897.158, P = 0.023) were independent risk factors for ETI-MV. The area under the ROC curve (AUC) of ROC showed that PaO2/FiO2 had the greatest predictive value for ETI-MV, with AUC of 0.903, sensitivity of 91.1% and specificity of 95.1% in case of cutoff value of 151 mmHg. The AUC of pulmonary infiltrating opacity distribution range was 0.809, the sensitivity of 85.2%, specificity of 78.6% when the cutoff value was ≥ 3/4 lung field. APACHE II scores had the lowest predictive value for selecting ETI-MV, with AUC of 0.704, sensitivity of 83.6% and specificity of 57.1% under the cutoff value was 16.5. CONCLUSIONS: For patients with ARDS caused by viral pneumonia, PaO2/FiO2 is still the classic reference for selecting ETI-MV, however, the distribution range of pulmonary infiltrating opacity and the systemic severity of the disease during 24 hours admitted to the RICU may provide supplemental helpful information to determine whether the patients choose ETI-MV, especially for moderate ARDS.

[Comparative study on pros and cons of sequential high-flow nasal cannula and non-invasive positive pressure ventilation immediately following early extubated patients with severe respiratory failure due to acute exacerbations of chronic obstructive pulmonary disease].

OBJECTIVE: To explore the pros and cons of sequential high-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) immediately following early extubated patients with severe respiratory failure (SRF) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so as to provide evidence for clinical selection of optimal scheme. METHODS: Consecutive AECOPD patients admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2019 to September 2020 were screened for enrollment. Patients were between 40 years old and 85 years old with acute exacerbation of bronchial-pulmonary infection, who received endotracheal intubation mechanical ventilation (ETI-MV) as the initial respiratory support method. The pattern of synchronous intermittent mandatory ventilation (SIMV) was used in the study. The parameters were set as follows: tidal volume (VT) 8 mL/kg, support pressure 10-15 cmH2O (1 cmH2O = 0.098 kPa), positive end-expiratory pressure (PEEP) 4-6 cmH2O and the ratio of inspiratory to expiratory time 1.5-2.5:1. Under these conditions, the plateau pressure (Pplat) was maintained less than 30 cmH2O. The minimum fraction of inspired oxygen was adjusted to keep the pulse oxygen saturation no less than 0.92. When the pulmonary infection control window (PIC window) occurred, the subjects were extubated immediately and randomly divided into two groups, with one group receiving HFNC (called HFNC group), the other group receiving NIPPV (called NIPPV group). Patients with failed sequential HFNC or NIPPV underwent tracheal re-intubation. The rate of tracheal re-intubation within 7 days of extubation, complications (such as nose and face crush injury and gastric distension), in-hospital mortality, duration of ETI before PIC window, length of RICU stay and length of hospital stay were compared, respectively. RESULTS: Forty-four patients were enrolled in the study, 20 in the HFNC group and 24 in the NIPPV group. There was no significant difference in the duration of ETI before PIC window between HFNC and NIPPV groups (hours: 95.9±13.1 vs. 91.8±20.4, P > 0.05). The rate of tracheal re-intubation within 7 days in the HFNC group was significantly higher than that in the NIPPV group [35.0% (7/20) vs. 4.2 % (1/24), P < 0.05]. However, the incidence of complication in the HFNC group was significantly lower than that in the NIPPV group [0% (0/20) vs. 25.0% (6/24), P < 0.05]. Compared with the NIPPV group, the in-hospital mortality in the HFNC group was slightly higher [5.0% (1/20) vs. 4.2% (1/24)], the length of RICU stay (days: 19.5±10.8 vs. 15.5±7.2) and the length of hospital stay (days: 27.4±12.2 vs. 23.3±10.9) were slightly longer, without statistical differences (all P > 0.05). CONCLUSIONS: For early extubated patients with SRF due to AECOPD, the compliance of sequential HFNC increased and the complications decreased significantly, but the final effect may be worse than sequential NIPPV.

[Expression of serous fibroblast growth factor 7 and related inflammatory factors in patients with acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the expression of fibroblast growth factor 7 (FGF7) and related inflammatory factors in the serum of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: A case control study was conducted. The patients with AECOPD admitted to the First Affiliated Hospital of Xinjiang Medical University from November 2016 to January 2020 were enrolled. The patients were divided into mild group [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio (FEV1/FVC) < 0.70, FEV1 percentage in predicted value (FEV1%) ≥ 80%], moderate group (FEV1/FVC < 0.70, 50% ≤ FEV1% < 80%), and severe group (FEV1/FVC < 0.70, 30% ≤ FEV1% < 50%) based on their lung function test results, with 20 patients in each group, and 20 patients with normal pulmonary function who underwent elective non-thoracic surgery such as gastrointestinal surgery and orthopedics surgery in the same period were selected as controls. The demographic data, FEV1/FVC, FEV1%, FVC, maximum mid-expiratory flow percentage in predicted value (MMEF%), 6-minute walking test (6MWT), and St George Respiratory Questionnaire (SGRQ) score were recorded respectively. Serum levels of FGF7, interleukins (IL-6, IL-1ß) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA). Pearson correlation was used to analyze the correlation between TNF-α and lung function. RESULTS: Compared with the normal pulmonary function group, the levels of FEV1/FVC, FEV1%, MMEF% and 6MWT in the mild, moderate and severe groups were significantly decreased, and the SGRQ scores were increased, the indicators continued to deteriorate with the aggravation of the disease, the statistical differences were found between severe group and normal pulmonary function group [FEV1/FVC: 0.39±0.09 vs. 0.81±0.04, FEV1%: (38.80±6.28)% vs. (109.58±13.80)%, MMEF%: (0.34±0.14)% vs. (2.69±0.99)%, 6MWT (m): 279.00±41.61 vs. 402.85±53.97, SGRQ scores: 34.95±6.71 vs. 2.60±2.06, all P < 0.05]. Compared with the normal pulmonary function group, the levels of FGF7 in the mild, moderate and severe groups were significantly lowered (ng/L: 6.31±2.65, 6.10±1.39, 6.64±1.77 vs. 8.29±3.51, all P < 0.05), but no significant difference was found among the mild, moderate and severe groups (all P > 0.05). Compared with the normal pulmonary function group, IL-6 and TNF-α levels were significantly increased in the mild, moderate and severe groups, and TNF-α increased with the aggravation of the disease, the statistical difference was found between severe group and normal pulmonary function group (ng/L: 7.42±2.28 vs. 3.83±0.92, P < 0.05). There was no significant difference in IL-1ß level between the normal pulmonary function group and the mild, moderate, severe groups. Correlation analysis showed that TNF-α was negatively correlated with FEV1/FVC and FEV1% (r values were -0.350 and -0.527, respectively, both P < 0.01). CONCLUSIONS: In AECOPD patients, serum FGF7 was decreased, while IL-6 and TNF-α were increased; however, with the aggravation of the disease, there was no significant change in the level of FGF7 in the peripheral blood, but the TNF-α level might be increased, accompanied by severe damage of small airway function.

Silencing miR-125b-5p attenuates inflammatory response and apoptosis inhibition in mycobacterium tuberculosis-infected human macrophages by targeting DNA damage-regulated autophagy modulator 2 (DRAM2).

Tuberculosis is one of the most important infectious diseases worldwide and macrophage apoptosis is the major host defense mechanism against TB. We attempted to characterize the role of miRNA (miR)-125b-5p on mycobacterium tuberculosis (Mtb) infection and macrophages behaviors in vitro. According to fluorescence-activated cell separation (FACS), primary monocytes (CD14+) in TB patients were accumulated, and apoptotic monocytes were decreased. Peripheral blood mononuclear cells (PBMCs)-derived macrophages (MDMs) and monocytic cells THP-1-derived macrophage-like cells (TDMs) in vitro were used to be infected with H37Rv. After infection, colony-forming units assay revealed the increase of bacterial activity, FACS demonstrated the decrease of apoptosis rate of MDMs and TDMs, as well as promoted levels of IL-6, TNF-α, Bax, and Bim and suppressed levels of IL-10 and Bcl-2, examined by enzyme-linked immunosorbent assay (ELISA) and western blot assay. Expression of miR-125b-5p and DNA damage-regulated autophagy modulator 2 (DRAM2) was examined, and real-time PCR and western blot assay showed that miR-125b-5p was upregulated, whereas DRAM2 was downregulated in primary monocytes and H37Rv-infected macrophages (MDMs and TDMs). Moreover, blocking miR-125b-5p could attenuated H37Rv-induced bacterial activity and inflammatory response of MDMs and TDMs, accompanied with apoptosis inhibition. Whereas these effects of miR-125b-5p knockdown were abolished by downregulating DRAM2. In mechanism, DRAM2 was a downstream target of miR-125b-5p, as evidenced by dual-luciferase reporter assay. Collectively, silencing miR-125b-5p could protect human macrophages against Mtb infection through promoting apoptosis and inhibiting inflammatory response via targeting DRAM2, suggesting a novel target for Mtb eliminating. Abbreviations: TB: tuberculosis; PBMCs: peripheral blood mononuclear cells; Mtb: mycobacterium tuberculosis; AFB: acid fast bacilli; FITC: fluorescein isothiocyanate; MDMs: monocytes-derived macrophages; TDMs: THP-1-derived macrophage-like cells; ERFP: Mtb-enhanced red fluorescent protein; CFU: colony-forming units; ELISA: enzyme-linked immunosorbent assay; FACS: fluorescence-activated cell separation; PI: propidium iodide; DRAM2: DNA damage-regulated autophagy modulator 2; Real-time PCR: real-time polymerase chain reaction; in-miR-125b-5p: miR-125b-5p inhibitor; si-DRAM2: siRNA against DRAM2.

[Timing of sequential noninvasive mechanical ventilation following early extubation in aged patients with severe community-acquired pneumonia].

OBJECTIVE: To explore the timing of sequential noninvasive positive pressure ventilation (NIPPV) following endotracheal intubation mechanical ventilation (ETI-MV) in aged patients with severe community-acquired pneumonia (SCAP). METHODS: A prospective cohort study was conducted. The SCAP patients aged ≥ 75 years old admitted to respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from July 2017 to August 2019 were enrolled. SCAP was diagnosed according to the criteria of Guidelines for the diagnosis and treatment of community-acquired pneumonia in adults in China (2016) published by Chinese Thoracic Society. ETI-MV was initially performed as respiratory support after RICU admission. Sequential NIPPV was performed immediately following extubation when the patients exhibited pulmonary infection abated (PIA) window. The gender, age, underlying diseases, and body temperature, heart rate (HR), respiratory rate (RR), oxygenation index (PaO2/FiO2) after RICU admission, as well as acute physiology and chronic health evaluation II (APACHE II) score, improved pneumonia score of British Thoracic Society (confusion, uremia, respiratory, blood pressure, age 65 years, CURB-65), and pneumonia severity index (PSI) score within 24 hours after RICU admission were recorded. The duration and times of ETI, the incidences of ventilator associated pneumonia (VAP) and aspiration, the duration of mechanical ventilation (MV), the length of RICU and hospital stay and RICU prognosis were also recorded. The patients were divided into the ETI ≤ 7 days group and the ETI > 7 days group according to the duration of ETI, and the clinical data were compared between the two groups. Multivariate Logistic regression analysis was used to screen the risk factors of aged patients with SCAP whose ETI was more than 7 days, and receiver operator characteristic (ROC) curve was drawn to evaluate the predictive value of risk factors. RESULTS: Fifty aged patients with SCAP were enrolled, with 24 patients in the ETI ≤ 7 days group and 26 in the ETI > 7 days group. Univariate analysis showed that compared with the patients with ETI ≤ 7 days, the incidences of concurrent cerebrovascular diseases [46.2% (12/26) vs. 16.7% (4/24)], VAP [61.5% (16/26) vs. 16.7% (4/24)] and aspiration [69.2% (18/26) vs. 25.0% (6/24)] were significantly increased in patients with ETI > 7 days (all P < 0.05). Multivariate Logistic regression analysis indicated that VAP and aspiration were independent risk factors of ETI > 7 days in the aged SCAP patients [VAP: odds ratio (OR) = 4.852, 95% confidence interval (95%CI) was 1.076-21.877, P = 0.040; aspiration: OR = 5.903, 95%CI was 1.474-23.635, P = 0.012]. ROC curve analysis showed that the area under ROC curve (AUC) of VAP for predicting ETI > 7 days in aged patients with SCAP was 0.724, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index were 61.54%, 83.33%, 80.00%, 66.67%, 3.69, 0.46 and 0.45, respectively. Similarly, the AUC of aspiration was 0.721, the sensitivity, specificity, PPV, NPV, PLR, NLR and Youden index were 69.23%, 75.00%, 75.00%, 69.23%, 2.77, 0.41 and 0.44, respectively. Analysis of prognostic indicators showed that compared with patients with ETI ≤ 7 days, the reintubation rate and RICU mortality were significantly increased in patients with ETI > 7 days [53.8% (14/26) vs. 4.2% (1/24), 38.5% (10/26) vs. 12.5% (3/24), both P < 0.05]. Moreover, the patients with ETI > 7 days had significantly prolonged total duration of MV, the length of RICU stay and total hospital stay as compared with the patients with ETI ≤ 7 days [total duration of MV (days): 23.8±11.8 vs. 11.3±3.1, length of RICU stay (days): 30.6±14.1 vs. 16.0±5.1, total length of hospital stay (days): 33.0±14.9 vs. 20.2±6.1, all P < 0.01]. CONCLUSIONS: Sequential NIPPV performed immediately following extubation within 7 days in the aged SCAP patients might reduce the mortality and shorten the duration of MV. The prolonged ETI duration because of the VAP or aspiration would lead to a reduced function of sequential NIPPV and an increased mortality of the aged patients with SCAP.

Circ_0038467 regulates lipopolysaccharide-induced inflammatory injury in human bronchial epithelial cells through sponging miR-338-3p.

BACKGROUND: Pneumonia is a common acute lower respiratory infection in children and elders. Circular RNAs (circRNAs) have recently been uncovered to play important roles in pneumonia. However, the function and mechanism of circ_0038467 in pneumonia remain elusive. METHODS: Cell viability and apoptosis were determined using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The levels of interleukin 6 (IL-6), IL-8 and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to assess the expression of related proteins. Circ_0038467 was characterized by Ribonuclease R (RNase) digestion and subcellular localization assays. The levels of circ_0038467 and miR-338-3p were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The direct interaction between circ_0038467 and miR-338-3p was validated by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: Our data indicated that lipopolysaccharide (LPS) induced an inflammatory injury in 16HBE cells by repressing cell viability and enhancing cell apoptosis and proinflammatory cytokines production. Circ_0038467 was upregulated and miR-338-3p was downregulated in LPS-treated 16HBE cells. Circ_0038467 knockdown or miR-338-3p overexpression attenuated LPS-induced 16HBE cell inflammatory injury. Moreover, circ_0038467 acted as a sponge of miR-338-3p in 16HBE cells. MiR-338-3p mediated the alleviated effect of circ_0038467 knockdown on LPS-induced 16HBE cell inflammatory injury. Additionally, the Janus kinase/ signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway was involved in the circ_0038467/miR-338-3p axis-mediated regulation in LPS-induced 16HBE cell inflammatory injury. CONCLUSIONS: The current work had led to the identification of circ_0038467 knockdown that alleviated LPS-induced inflammatory injury in 16HBE cells at least partly through sponging miR-338-3p and regulating JAK/STAT3 pathway, highlighting novel molecular targets for the treatment of pneumonia.

[Predictive factors for failure of non-invasive positive pressure ventilation in immunosuppressed patients with acute respiratory failure].

OBJECTIVE: To evaluate the predictive factors for failure of non-invasive positive pressure ventilation (NIPPV) in immunosuppressed patients with acute respiratory failure (ARF). METHODS: The clinical data of 118 immuno-deficient patients treated with NIPPV in the respiratory and intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2012 to August 2017 were retrospectively analyzed. The patients were divided into a non-endotracheal intubation (ETI) group (n = 62) and ETI group (n = 56) according to whether ETI was performed during the hospitalization period or not. Each observed indicator was analyzed by univariate analysis, and factors leading to failure of NIPPV were further analyzed by Logistic regression. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of risk factors for failure of NIPPV in immunosuppressed patients with ARF. RESULTS: The non-intubation rate for NIPPV in immunosuppressed patients was 50.8% (60/118). Compared with the non-ETI group, the body temperature, pH value in the ETI group were significantly increased, the partial pressure of arterial carbon dioxide (PaCO2) was significantly decreased, the ratio of oxygenation index (PaO2/FiO2) < 100 mmHg (1 mmHg = 0.133 kPa), acute physiology and chronic health evaluation II (APACHE II) score ≥ 20, and the number of cases requiring catecholamine were significantly increased, the mortality was significantly increased. Multivariate Logistic regression analysis showed that the APACHE II score ≥ 20 [odds ratio (OR) = 15.274, 95% confidence internal (95%CI) = 2.175-107.252, χ2 = 7.516, P = 0.006], PaO2/FiO2 < 100 mmHg (OR = 0.075, 95%CI = 0.014-0.408, χ2 = 8.968, P = 0.003), and need for catecholamine (OR = 35.736, 95%CI = 6.974-183.124, χ2 = 18.400, P < 0.001) were independent risk factors for failure of NIPPV. ROC curve analysis showed that the APACHE II score ≥ 20 and PaO2/FiO2 < 100 mmHg could predict failure of NIPPV, the area under ROC curve (AUC) of the APACHE II score ≥ 20 was 0.787, the sensitivity was 83.93%, the specificity was 69.35%, the positive predict value (PPV) was 71.21%, the negative predict value (NPV) was 82.69%, the positive likelihood ratio (PLR) was 2.74, the negative likelihood ratio (NLR) was 0.23, and Youden index was 0.53; the AUC of PaO2/FiO2 < 100 mmHg was 0.757, the sensitivity was 80.65%, the specificity was 66.07%, the PPV was 68.18%, the NPV was 78.85%, the PLR was 2.38, the NLR was 0.29, and Youden index was 0.47. CONCLUSIONS: 50.8% of immunocompromised and ARF patients treated with NIPPV did not require ETI, which is independent of the etiology of ARF. APACHE II score ≥ 20, PaO2/FiO2 < 100 mmHg, and the need for catecholamine are predictive factors for failure of NIPPV in immunocompromised patients.

Adding an arch support to a heel lift improves stability and comfort during gait.

Heel lifts have been widely used as a conservative treatment for some musculoskeletal problems and complaints. However, the heel rise caused by heel lifts may also affect the plantar pressure distribution and stability during walking. This study aimed to test whether adding an arch support to a heel lift would improve its stability and comfort through comparing the center of pressure (COP) during walking and subjective ratings between heel lifts with and without an arch support. Fifteen healthy male participants were asked to walk along an 8m walkway while wearing high-cut footwear with the control heel lifts and the heel lifts with an arch support. A Footscan pressure plate was used to measure the COP during walking. Subjective ratings including medial-lateral control, dynamic foot/shoe fitting and overall comfort were assessed for each participant. The results showed that compared to the control condition, the COP trajectory was medially shifted during stance phase of gait in the arch support condition. The maximum displacements and velocity of medial-lateral COP in the forefoot contact phase were smaller in the arch support condition than in the control condition. Adding an arch support to a heel lift also significantly improved the subjective ratings in terms of the medial-lateral control, dynamic foot/shoe fitting and overall comfort. The findings of this study suggest that adding an arch support to a heel lift could improve its stability and comfort during walking.

An optimized design of in-shoe heel lifts reduces plantar pressure of healthy males.

Conventional heel lift with a flat surface increases the risk of foot problems related to higher plantar pressure and decreased stability. In this study, an optimized design of in-shoe heel lifts developed to maintain the midfoot function was tested to investigate if the plantar pressure distribution was improved. The design was based on three dimensional foot plantar contour which was captured by an Infoot 3D scanning system while the heel was elevated by a heel wedge. To facilitate midfoot function, an arch support was designed to support the lateral longitudinal arch, while allowing functional movement of the medial longitudinal arch. Twenty healthy male subjects were asked to walk along an 8m walkway while wearing high-cut footwear with and without the optimized heel lift. Peak pressure, contact area and force-time integral were measured using the Pedar insole system. Range and velocity of medial-lateral center of pressure during forefoot contact phase and foot flat phase were collected using a Footscan pressure plate. Compared to the shoe only condition, peak pressure under the rearfoot decreased with the optimized heel lift, while no increase of peak pressure was observed under the forefoot and midfoot regions, indicating improved plantar pressure distribution. The findings of this study suggest that this optimized heel lift has better biomechanical performance than a conventional flat heel lift. Results from this study may have implications for insole and shoe last design, especially for people who need additional heel height without sacrificing midfoot function.

High-Mobility Group Box-1 Protein Disrupts Alveolar Elastogenesis of Hyperoxia-Injured Newborn Lungs.

Although high-mobility group box-1 (HMGB1) levels in tracheal aspirates are associated with the pathological features of bronchopulmonary dysplasia (BPD), the role of HMGB1 in the terminal stage of abnormal alveologenesis has not yet been understood. In this study, we addressed the role of HMGB1 in the elastogenesis disruption in the lungs of newborn mice with BPD. We found that elevations of whole lung HMGB1 level were associated with impaired alveolar development and aberrant elastin production in 85% O2-exposed lungs. HMGB1 neutralizing antibody attenuated the structural disintegration developed in hyperoxia-damaged lungs. Furthermore, HMGB1 inhibition rescued the neutrophil influx in hyperoxia-injured lung and partially abolished the mRNA level of the proinflammatory mediators, interleukin (IL)-1ß and transforming growth factor (TGF)-ß1. These data suggested that pulmonary HMGB1 plays an important role in the disruption of elastogenesis in the terminal stage of lung development through reduced pulmonary inflammatory response.