Conservative versus liberal oxygen therapy for intensive care unit patients: meta-analysis of randomized controlled trials.

BACKGROUND: It remains unclear whether conservative oxygen therapy (COT) or liberal oxygen therapy (LOT) is more beneficial to the clinical outcomes of intensive care unit (ICU) patients. We systematically reviewed the efficacy and safety of conservative versus liberal oxygen therapy for ICU patients. METHODS: We systematically searched PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, MedRxiv, and BioRxiv for reports on randomized controlled trials (RCTs) that compared the effects of COT versus LOT on the clinical outcomes of ICU patients published in English before April 2024. The primary outcome was the mortality rate, secondary outcomes included ICU and hospital length of stay, days free from mechanical ventilation support (MVF), vasopressor-free time (VFT), and adverse events. RESULTS: In all, 13 RCTs involving 10,632 patients were included in analyses. Meta-analysis showed COT did not reduce mortality at 30-day (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.94 to 1.09, I2 = 42%, P = 0.78), 90-day (RR = 1.01, 95% CI 0.95 to 1.08, I2 = 9%, P = 0.69), or longest follow-up (RR = 1.00, 95% CI 0.95 to 1.06, I2 = 22%, P = 0.95) compared to LOT in ICU patients. In subgroup analyses, no significant difference was observed between the two groups in terms of the different ICU, baseline P/F, and actual PaO2. In addition, COT did not affect ICU length of stay, hospital length of stay, or VFT, it only affected MVF days. CONCLUSIONS: COT did not reduce all-cause mortality in ICU patients. Further RCTs are urgently needed to confirm the impact of COT strategy on specific populations.

Comparison between high-flow nasal cannula and conventional oxygen therapy in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) are important respiratory support strategies for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the results are conflicting for the risk of intubation with HFNC as compared to COT. OBJECTIVES: We systematically synthesized the outcomes of HFNC relative to COT in COVID-19 patients with AHRF and evaluated these outcomes in relevant subpopulations. DESIGN: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES AND METHODS: We searched PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, medRxiv, BioRxiv, and the Cochrane Central Register of Controlled Trials for randomized controlled trials and observational studies that compared the efficacy of HFNC with COT in patients with COVID-19-related AHRF. Primary outcomes were intubation rate and mortality rate. Secondary outcomes were the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), respiratory rate, hospital length of stay, intensive care unit (ICU) length of stay, and days free from invasive mechanical ventilation. RESULTS: In total, 20 studies with 5732 patients were included. We found a decreased risk of requiring intubation in HFNC compared to COT [odds ratio (OR) = 0.61, 95% confidence interval (CI): 0.46-0.82, p = 0.0009, I2 = 75%]. Similarly, we found HFNC was associated with lower risk of intubation rate compared to COT in the subgroup of patients with baseline PaO2/FiO2 < 200 mmHg (OR = 0.69, 95% CI: 0.55-0.86, p = 0.0007, I2 = 45%), and who were in ICU settings at enrollment (OR = 0.57, 95% CI: 0.38-0.85, p = 0.005, I2 = 80%). HFNC was associated with an improvement of PaO2/FiO2 and respiratory rate compared to COT. The use of HFNC compared to COT did not reduce the mortality rate, days free from invasive mechanical ventilation, hospital length of stay, or ICU length of stay. CONCLUSION: Compared to COT, HFNC may decrease the need for tracheal intubation in patients with COVID-19-related AHRF, particularly among patients with baseline PaO2/FiO2 < 200 mmHg and those in ICU settings. TRIAL REGISTRATION: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022339072).

Efficacy and Safety of Sevelamer Carbonate in Chinese Nondialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized, Double-Blind, Parallel-Group Study.

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia. Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4-12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8. Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (-0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly (p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group (p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group. Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia.

Comparison between high-flow nasal cannula and noninvasive ventilation in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are important treatment approaches for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the differential impact of HFNC versus NIV on clinical outcomes of COVID-19 is uncertain. OBJECTIVES: We assessed the effects of HFNC versus NIV (interface or mode) on clinical outcomes of COVID-19. METHODS: We searched PubMed, EMBASE, Web of Science, Scopus, MedRxiv, and BioRxiv for randomized controlled trials (RCTs) and observational studies (with a control group) of HFNC and NIV in patients with COVID-19-related AHRF published in English before February 2022. The primary outcome of interest was the mortality rate, and the secondary outcomes were intubation rate, PaO2/FiO2, intensive care unit (ICU) length of stay (LOS), hospital LOS, and days free from invasive mechanical ventilation [ventilator-free day (VFD)]. RESULTS: In all, 23 studies fulfilled the selection criteria, and 5354 patients were included. The mortality rate was higher in the NIV group than the HFNC group [odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.51-0.84, p = 0.0008, I2 = 60%]; however, in this subgroup, no significant difference in mortality was observed in the NIV-helmet group (OR = 1.21, 95% CI: 0.63-2.32, p = 0.57, I2 = 0%) or NIV-continuous positive airway pressure (CPAP) group (OR = 0.77, 95% CI: 0.51-1.17, p = 0.23, I2 = 65%) relative to the HFNC group. There were no differences in intubation rate, PaO2/FiO2, ICU LOS, hospital LOS, or days free from invasive mechanical ventilation (VFD) between the HFNC and NIV groups. CONCLUSION: Although mortality was lower with HFNC than NIV, there was no difference in mortality between HFNC and NIV on a subgroup of helmet or CPAP group. Future large sample RCTs are necessary to prove our findings. REGISTRATION: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022321997).

Effectiveness of the use of a high-flow nasal cannula to treat COVID-19 patients and risk factors for failure: a meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread globally, and many patients with severe cases have received oxygen therapy through a high-flow nasal cannula (HFNC). OBJECTIVES: We assessed the efficacy of HFNC for treating patients with COVID-19 and risk factors for HFNC failure. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of randomized controlled trials (RCTs) and observational studies of HFNC in patients with COVID-19 published in English from January 1st, 2020 to August 15th, 2021. The primary aim was to assess intubation, mortality, and failure rates in COVID-19 patients supported by HFNC. Secondary aims were to compare HFNC success and failure groups and to describe the risk factors for HFNC failure. RESULTS: A total of 25 studies fulfilled selection criteria and included 2851 patients. The intubation, mortality, and failure rates were 0.44 (95% confidence interval (CI): 0.38-0.51, I2 = 84%), 0.23 (95% CI: 0.19-0.29, I2 = 88%), and 0.47 (95% CI: 0.42-0.51, I2 = 56%), respectively. Compared to the success group, age, body mass index (BMI), Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, D-dimer, lactate, heart rate, and respiratory rate were higher and PaO2, PaO2/FiO2, ROX index (the ratio of SpO2/FiO2 to respiratory rate), ROX index after the initiation of HFNC, and duration of HFNC were lower in the failure group (all Ps < 0.05). There were also more smokers and more comorbidities in the failure group (all Ps < 0.05). Pooled odds ratios (ORs) revealed that older age (OR: 1.04, 95% CI: 1.01-1.07, P = 0.02, I2 = 88%), a higher white blood cell (WBC) count (OR: 1.06, 95% CI: 1.01-1.12, P = 0.02, I2 = 0%), a higher heart rate (OR: 1.42, 95% CI: 1.15-1.76, P < 0.01, I2 = 0%), and a lower ROX index(OR: 0.61, 95% CI: 0.39-0.95, P = 0.03, I2 = 93%) after the initiation of HFNC were all significant risk factors for HFNC failure. CONCLUSIONS: HFNC is an effective way of providing respiratory support in the treatment of COVID-19 patients. Older age, a higher WBC count, a higher heart rate, and a lower ROX index after the initiation of HFNC are associated with an increased risk of HFNC failure.

Effect of Mask Selection on the Leak Test in Ventilators Designed for Noninvasive Ventilation.

BACKGROUND: The mask leak test used for modern noninvasive ventilators can detect the leak characteristics of masks that are not recommended by the manufacturer, but it has not yet been determined whether this method is acceptable. METHODS: A noninvasive ventilator equipped with a single-limb circuit and an oronasal mask was connected to a lung simulator. The ventilator was set to S/T mode, and inspiratory positive airway pressure/expiratory positive airway pressure was set to 10/5, 15/5, and 20/5 cm H2O, respectively. Eight nonmanufacturer-recommended oronasal masks were connected to the ventilator. The lung simulator was used to simulate COPD, restrictive disease, and normal lung, respectively. When switching between masks, the mask leak test was set to "Cancel" or "Start Test" in the noninvasive ventilator. The parameters displayed on the lung simulator and ventilator were recorded before and after the mask leak test. RESULTS: There were no significant difference before versus after the mask leak test for any lung simulator parameter, including trigger performance (ie, time from the beginning of the simulated inspiratory effort to the lowest value of airway pressure needed to trigger the ventilator, the magnitude of airway pressure drop needed to trigger, and time to trigger), inspiratory pressure delivery, PEEP, tidal volume, and displayed peak inspiratory pressure (all differences < 10%). At different noninvasive ventilation settings, tidal volumes displayed on the ventilator of the 3 masks were significantly different before and after mask leak test (all P < .05, and difference rate > 10%). CONCLUSIONS: The mask leak test had no effect on the ventilator performance when masks not recommended by the manufacturer were used, but tidal volume monitoring may be more accurate when some masks were used.

Adult with mass burnt lime aspiration: A case report and literature review.

BACKGROUND: Foreign body aspiration mainly occurs in children, which can cause a severe concurrent syndrome and even death without timely treatment. As a rare foreign body, aspiration of lime is seldom reported, and most cases involve a small amount of hydrated lime. Although the symptoms are usually severe, the prognosis is good after suitable treatment. Experience of treatment for lime aspiration is lacking, and this report provides novel evidence for treatment of mass burnt lime aspiration using bronchoscopy. CASE SUMMARY: We report an adult with a large amount of burnt lime aspiration. Because of delay in clearance of the inhaled lime in the trachea and bronchus at the local hospital, he suffered several severe complications, including complete occlusion of the right primary bronchus, aeropleura, aerodermectasia, pneumomediastinum, secondary infection and hypoxemia at 4 d after injury. After transferring to our department, bronchoscopy was immediately carried out to clear the lime in the major airway, using foreign body forceps, biopsy forceps, puncture needle, and hairbrush. The patient's condition recovered rapidly and at 3-months' follow-up, he demonstrated good recovery of the bronchus and lung parenchyma. CONCLUSION: After mass lime aspiration, flexible fiberoptic bronchoscopy is suggested as early as possible, using clamping, flushing or cryotherapy.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.

The Effect of Different Interfaces on the Aerosol Delivery with Vibrating Mesh Nebulizer During Noninvasive Positive Pressure Ventilation.

Background: The effect of different interfaces on the aerosol delivery with vibrating mesh nebulizer during noninvasive positive pressure ventilation (NIV) is not clear. Materials and Methods: Noninvasive ventilator and four interfaces were connected to IngMar ASL 5000 lung simulator. Meanwhile, the vibrating mesh nebulizer was connected to a ventilator circuit to simulate the nebulization during noninvasive ventilation. The nebulizer position was placed at proximal position (near the mask) and distal position (15 cm away from the mask); the inspiratory positive airway pressure (IPAP) and the expiratory positive airway pressure (EPAP) were set to 16/4, 16/8, 20/4, and 20/8 cmH2O, respectively. The aerosol was collected through a disposable filter placed between the simulated lung and the mask, after which the aerosol delivery was calculated. Meanwhile, we recorded the inspiratory tidal volume and the mean inspiratory flow. Results: The aerosol delivery varied between 1.7% ± 0.0% and 21.1% ± 1.1%. Only when EPAP was set to 4 cmH2O, the statistical difference in aerosol delivery was observed between the two types of interface, and between different leak port locations (p < 0.01; p = 0.04, respectively). When IPAP/EPAP was set to 16/4 and 20/4 cmH2O, respectively, at different nebulizer positions, there was a statistical difference between the interface with the same type but different leak port locations and between the interface with same leak port location but different inner volumes (all p < 0.01). Also, there was a correlation between the aerosol delivery and interface volume (p < 0.01, R2 = 0.55; p < 0.01, R2 = 0.51, respectively), and between aerosol delivery and the intentional leak of interfaces (p < 0.01, R2 = 0.59; p < 0.01, R2 = 0.48, respectively). When EPAP was set to 4 and 8 cmH2O, respectively, the aerosol delivery of nebulizer distal position was significantly higher than that of proximal position (12.2% ± 5.0% vs. 9.1% ± 4.1%, p < 0.05; 2.5% ± 0. 5% vs. 2.1% ± 0.3%, p < 0.01, respectively). Conclusion: Interfaces have a significant effect on aerosol delivery during NIV. The interfaces with different inner volumes, intentional leak, and leak port location may all have an effect on aerosol delivery. The addition of a 15 cm tube between the nebulizer and the mask significantly increases the aerosol delivery.

The efficacy and tolerance of prone positioning in non-intubation patients with acute hypoxemic respiratory failure and ARDS: a meta-analysis.

BACKGROUND AND AIMS: The application of prone positioning with acute hypoxemic respiratory failure (AHRF) or acute respiratory distress syndrome (ARDS) in non-intubation patients is increasing gradually, applying prone positioning for more high-flow nasal oxygen therapy (HFNC) and non-invasive ventilation (NIV) patients. This meta-analysis evaluates the efficacy and tolerance of prone positioning combined with non-invasive respiratory support in patients with AHRF or ARDS. METHODS: We searched randomized controlled trials (RCTs) (prospective or retrospective cohort studies, RCTs and case series) published in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 1 July 2020. We included studies that compared prone and supine positioning with non-invasive respiratory support in awake patients with AHRF or ARDS. The meta-analyses used random effects models. The methodological quality of the RCTs was evaluated using the Newcastle-Ottawa quality assessment scale. RESULTS: A total of 16 studies fulfilled selection criteria and included 243 patients. The aggregated intubation rate and mortality rate were 33% [95% confidence interval (CI): 0.26-0.42, I2 = 25%], 4% (95% CI: 0.01-0.07, I2 = 0%), respectively, and the intolerance rate was 7% (95% CI: 0.01-0.12, I2 = 5%). Prone positioning increased PaO2/FiO2 [mean difference (MD) = 47.89, 95% CI: 28.12-67.66; p < 0.00001, I2 = 67%] and SpO2 (MD = 4.58, 95% CI: 1.35-7.80, p = 0.005, I2 = 97%), whereas it reduced respiratory rate (MD = -5.01, 95% CI: -8.49 to -1.52, p = 0.005, I2 = 85%). Subgroup analyses demonstrated that the intubation rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 34% and 21%, respectively; and the mortality rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 6% and 0%, respectively. PaO2/FiO2 and SpO2 were significantly improved in COVID-19 patients and non-COVID-19 patients. CONCLUSION: Prone positioning could improve the oxygenation and reduce respiratory rate in both COVID-19 patients and non-COVID-19 patients with non-intubated AHRF or ARDS.The reviews of this paper are available via the supplemental material section.

Acute mediastinitis associated with tracheobronchial tuberculosis and aspergillosis: a case report and literature review.

Acute mediastinitis (AM) is a rare but life-threatening disease. Here, we report a case of AM secondary to endobronchial tuberculosis (EBTB) and pseudomembranous Aspergillus tracheobronchitis (PMATB) co-infection. EBTB was confirmed by tissue culture for Mycobacterium tuberculosis and GeneXpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) detection (simultaneous detection of M. tuberculosis and resistance to rifampin) using endobronchial biopsies; PMATB was confirmed by histopathology. Even with antibiotic treatment and systemic support treatment, the patient died of massive hemoptysis on day 10 after admission. When immunocompromised hosts have AM, especially with central airway involvement, EBTB and aspergillosis should be considered potential causes. Bronchoscopy is helpful for rapid diagnosis and administering precise treatment.

Factors affecting FiO2 and PEEP during high-flow nasal cannula oxygen therapy: A bench study.

INTRODUCTION: It is unknown if set-flow, peak inspiratory flow (PIF), tidal volume and set fraction of inspired O2 (FiO2 ) affect actual-FiO2 and positive end-expiratory pressure (PEEP) during high-flow nasal cannula (HFNC) oxygen therapy. In addition, the extent of their influence is also unknown. OBJECTIVES: To investigate the effects of set-FiO2 , set-flow, PIF and tidal volume on the actual-FiO2 and PEEP during HFNC oxygen therapy. METHODS: A lung simulation model was used to study the factors that might affect FiO2 and PEEP during HFNC therapy in vitro. These factors included set-flow (20, 40, 60, 80 and 120 L/min), PIF (40, 80 and 120 L/min), tidal volume (400 and 600 mL), and set-FiO2 (30%, 50% and 70%). Actual-FiO2 and PEEP were recorded for 10 consecutive breaths. Actual-FiO2 and PEEP were compared under different conditions. Multivariate linear regressions were performed to investigate the effects of these factors on actual-FiO2 and PEEP. RESULTS AND CONCLUSION: Regression formula were: (a) actual-FiO2 as the dependent variable: actual FiO2  = 2.71 + 0.78 × set-FiO2  + 0.17 × set-flow - 0.09 × PIF (F test, F = 3866.62, P < 0.001, R2  = 0.94), (b) PEEP as the dependent variable: PEEP = 1.35 + 0.15 × set-flow - 0.02 × PIF + 0.01 × tidal volume (F test, F = 4082.39, P < 0.001, R2  = 0.95). The following factors were found to affect actual-FiO2 (in descending order): set-FiO2 , set-flow and PIF. Tidal volume had little effect on actual-FiO2 . Factors which affected PEEP were (in descending order): set-flow, peak inspiratory flow and tidal volume.

Effect of Jet Nebulization on Noninvasive Positive-Pressure Ventilation Administered with Noninvasive or Intensive Care Unit Ventilators: A Bench Study.

BACKGROUND: Most of the patients on noninvasive positive pressure ventilation require aerosol inhalation therapy to moisturize the airways or deliver drugs in acute settings. However, the effect of jet nebulization on noninvasive positive pressure ventilation (NPPV) has not been determined. OBJECTIVES: This study was designed to investigate the impact of jet nebulization on NPPV applied in ventilators. METHODS: Aerosol therapy during NPPV was conducted in a simulated lung. The jet nebulizer was connected at both the distal and proximal end of the exhalation valve for the noninvasive ventilators, while it was placed both in front of the Y tube proximal to the patient and at 15 cm distance from the Y-tube inspiratory limb distal to the patient for the intensive care unit (ICU) ventilators. Driving flow was set at 4 and 8 L/min, respectively. RESULTS: TPmin (time from the beginning of the lung simulator's inspiratory effort to the lowest value of airway pressure needed to trigger the ventilator), Ttrig (time to trigger), and Ptrig (the magnitude of airway pressure drop needed to trigger) were not significantly altered by jet nebulization in the noninvasive ventilators, while they were significantly increased in the ICU ventilators. The greater the driving flow, the stronger the impact on TPmin, Ttrig, and Ptrig. The actual tidal volume and control performance were not significantly affected by jet nebulization in either noninvasive or ICU ventilators. The tidal volume monitored was significantly increased at 8 L/min driving flow. The greater the driving flow, the stronger the impact on the tidal volume monitored. CONCLUSION: The effect of jet nebulization on NPPV was different when compared to invasive ventilation. Jet nebulization only affected the tidal volume monitored in the noninvasive ventilator. Jet nebulization also affected the triggering performance and tidal volume monitored in the ICU ventilator.

Plasma microRNA panel is a novel biomarker for focal segmental glomerulosclerosis and associated with podocyte apoptosis.

Focal segmental glomerulosclerosis (FSGS) is a frequent glomerular disease, and is the common cause of nephrotic syndrome. However, there is no validated diagnostic blood biomarker for FSGS. Here, we performed a real-time PCR-based high-throughput miRNA profiling to identify the plasma signature for FSGS. We found four miRNAs (miR-17, miR-451, miR-106a, and miR-19b) were significantly downregulated in the plasma of FSGS patients (n = 97) compared with healthy controls (n = 124) in the training, validation, and blinded-test phases. The miRNA panel produced an AUC value of 0.82, and was associated with FSGS severity and histologic classification. A three-miRNA panel, including miR-17, miR-451, and miR-106a was related to FSGS remission. Furthermore, the downregulation of plasma-miRNA signature was not detected in disease controls (n = 119) such as IgA nephropathy (IgAN), mesangial proliferative glomerulonephritis (MSPGN), and membranous nephropathy (MN), and the miRNA panel discriminated between FSGS and disease controls. Pathway analysis showed that the four-miRNA panel may cooperatively regulate the pathways involved in the development of FSGS, such as apoptosis. We identified that phosphatase and tensin homolog (PTEN), Bcl-2-like protein 11 (BCL2L11), and chemokine (C-X-C motif) ligand 14 (CXCL14) were targets of miR-106a in human podocyte. Additionally, miR-106a overexpression suppressed podocyte apoptosis in vitro and the downregulation of four-miRNA panel probably resulted in the enhanced apoptosis in podocyte during FSGS development. Taken together, our data show that the plasma-miRNA panel is a potential independent diagnostic and prognostic factor for FSGS. Above miRNAs are involved in FSGS pathogenesis through regulating podocyte apoptosis.

Efficacy of N-Acetylcysteine in Preventing Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis Study.

PURPOSE: To evaluate whether perioperative N-acetylcysteine (NAC) administration reduces the risk of cardiac surgery associated acute kidney injury (CSA-AKI). MATERIALS AND METHODS: A systematic literature review (Medline, PubMed, Cochrane, Biomedical central, Google Scholar) identified 10 studies (1391 patients; 695 NAC and 696 placebo) that compared the efficacy and adverse effects of perioperative NAC administration for CSA-AKI prevention in adults undergoing elective cardiac surgery. Meta-analysis was performed using Comprehensive Meta-Analysis statistical software. RESULTS: Patients in the NAC-treated and placebo groups had similar rate of CSA-AKI occurrence, change in creatinine levels, as well as the in-hospital mortality rate (RR = 0.841, 95% CI = 0.691 to 1.023, p = 0.083; pooled difference in means = -0.328, 95% CI = -0.712 to 0.056, p = 0.094; RR = 0.741, 95% CI = 0.388 to 1.418, p = 0.366, respectively). CONCLUSIONS: Our study does not support perioperative NAC administration as a mean to reduce the risk of CSA-AKI.

Which Nebulizer Position Should Be Avoided? An Extended Study of Aerosol Delivery and Ventilator Performance during Noninvasive Positive Pressure Ventilation.

BACKGROUND: Research on the effect of nebulizer location on aerosol delivery during noninvasive ventilation has reached inconsistent conclusions. OBJECTIVE: To investigate the effects of nebulizer position on aerosol delivery efficiency and ventilator performance during noninvasive ventilation. METHODS: The Active Servo Lung 5000 respiratory simulation system (ASL5000) was used to simulate a COPD patient. The noninvasive ventilator was set to the spontaneous breathing mode. Six nebulizer positions, 2 exhalation valve types (single-arch exhalation port and whisper swivel), 4 combinations of inspiratory and expiratory pressure, and 2 respiratory rates were used. RESULTS: Significant differences between nebulizer positions existed in aerosol delivery (p < 0.05). Aerosol delivery efficiency was lower for nebulizer locations on either side of the exhalation valve and next to the ventilator outlet. When the nebulizer was located between the exhalation valve and the simulated lung, increased inspiratory pressure increased and increased expiratory pressure decreased delivery efficiency (both p < 0.05). When the nebulization device was located between the exhalation valve and the ventilator, no obvious trend was observed. Compared to baseline, nebulization lowered the air leakage volume displayed on the ventilator. There were no differences in ventilator performance between different nebulizer positions. CONCLUSIONS: The closer the nebulizer was to the exhalation valves or ventilator, the lower the aerosol delivery efficiency. Nebulizer position had little clinically significant effect on ventilator performance.

Curcumin Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells through the Inhibition of Akt/mTOR Pathway.

Curcumin has exhibited a protective effect against development of renal fibrosis in animal models, however, its underlying molecular mechanisms are largely unclear. Therefore, we investigated the anti-fibrosis effects of curcumin in transforming growth factor-ß1 (TGF-ß1)-induced epithelial-to-mesenchymal transition (EMT), and the mechanism by which it mediates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Human kidney tubular epithelial cells (HKCs) were treated with TGF-ß1 or curcumin alone, or TGF-ß1 in combination with curcumin. The effect of curcumin on cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of E-cadherin, cytokeratin, vimentin, alpha smooth muscle actin (α-SMA), fibroblast-specific protein 1 (FSP1) and key proteins of Akt/mammalian target of rapamycin (mTOR) pathway were analyzed by immunocytochemistry, real-time PCR and Western blot. Low dose curcumin (3.125 and 25 µmol/L) effectively promoted HKC proliferation. When HKCs were co-incubated with TGF-ß1 and curcumin for 72 h, curcumin maintained the epithelial morphology in a dose-dependent manner, decreased expression of vimentin, α-SMA and FSP1 normally induced by TGF-ß1, and increased expression of E-cadherin, cytokeratin. Importantly, we found that curcumin reduced Akt, mTOR and P70S6K phosphorylation, effectively suppressing the activity of the Akt/mTOR pathway in HKCs. Curcumin also promoted HKC proliferation, and antagonized TGF-ß1-driven EMT through the inhibition of Akt/mTOR pathway activity, which may suggest an alternative therapy for renal fibrosis.

[Effect of Chinese drugs for strengthening Pi, harmonizing Wei, and dispersing blood stasis on the expression of gastric mucosal heat shock protein 70 in chronic atrophic gastritis patients].

OBJECTIVE: To observe the effect of Chinese drugs for strengthening Pi, harmonizing Wei, and dispersing blood stasis (CDSPHWDBS) on the expression of gastric mucosal heat shock protein 70 (HSP70) in chronic atrophic gastritis (CAG) patients. METHODS: A total of 100 CAG patients were assigned to the control group and the treatment group by random digit table, 50 in each group. Patients in the control group took Folic Acid Tablet 10 mg each time, 3 times per day. Those in the treatment group took CDSPHWDBS, 100 mL each time, once per day. The treatment course was 6 months for all. Clinical symptoms and signs, endoscopic and histopathological changes were observed before and after treatment in the two groups. The expression of gastric mucosal HSP70 in CAG patients was determined using SP immunohistochemistry. Data were collected by HPIAS-1 000 pathological graphic analysis system, and its expression semi-quantitatively analyzed. RESULTS: The total effective rate of clinical Chinese medical symptoms and signs was 88. 0% (44/50 cases) in the treatment group and 56. 0% (28/50 cases) in the control group, with significant difference between the two groups (P <0. 01). The improvement rate of endoscopic manifestations such as congestion and edema, erosion, bile regurgitation, pale gastric mucosa, exposed blood vessels, particles proliferation in the treatment group were superior to those in the control group (P <0. 05). The total effective rate of atrophy was 80. 0% (40/50 cases) in the treatment group and 54. 0% (27/50 cases) in the control group, with significant difference between the two groups (P<0. 01). The effective rate of intestinal metaplasia was 75. 0% (12/16 cases) in the treatment group and 33.3% (5/15 cases) in the control group, with significant difference between the two groups (P < 0. 05). The optical density value of gastric mucosal HSP70 was significantly elevated in the two groups after treatment (both P <0. 05). It was higher in the treatment group than in the control group after treatment with significant difference (P <0. 01). CONCLUSION: CDSPHWDBS had obvious effect in treatment of CAG and could improve pathological changes of precancerous lesions possibly by promoting the expression of gastric mucosal HSP70 in CAG patients.

Influence of exhalation valve and nebulizer position on albuterol delivery during noninvasive positive pressure ventilation.

BACKGROUND: Early studies have found better clinical efficiency when a nebulizer was used with noninvasive positive pressure ventilation (NPPV), compared with spontaneous breathing without NPPV. However, very limited research addressed factors that might affect aerosol delivery. This study aimed to investigate the influence of exhalation valves and nebulizer positions on aerosol delivery during NPPV. METHODS: We determined the efficiency of aerosol delivery in patients receiving NPPV with a lung model that simulates spontaneous breathing. Single-arch exhalation port, plateau exhalation valve, and whisper swivel were chosen as exhalation valves under different levels of inspiratory and expiratory pressures. A nebulizer was filled with 1 mL of 0.5% albuterol solution in 3 mL of normal saline, driven with 8 L/min oxygen, and placed at either a proximal position in the ventilator circuit (near the ventilator outlet, where humidifiers are usually connected) or a distal position in the ventilator circuit (between exhalation valve and lung model connection). Albuterol was collected by filters and then measured by ultraviolet spectrophotometry. The velocities of gas flow were also measured at different nebulizer positions. RESULTS: Significant differences in the gas flow velocity were shown between proximal and distal positions of the breathing circuit under four combinations of inspiratory and expiratory pressure levels (15/5, 15/10, 25/5, and 25/10 cmH2O) (p<0.05). When the nebulizer was positioned distally, the single-arch exhalation port had the highest aerosol delivery, and the whisper swivel had the lowest aerosol delivery (p<0.05). When the nebulizer was placed proximally, the single-arch exhalation port had lower efficiency of aerosol delivery than the whisper swivel and plateau exhalation valve (p<0.05). In addition, higher inspiratory pressure was associated with increased aerosol delivery (p<0.05). The influence of expiratory pressure on aerosol delivery appeared too complex to predict. CONCLUSIONS: The type of exhalation valve and the position of the nebulizer in the ventilator circuit have a significant influence on the efficiency of aerosol delivery during NPPV. As a result, with different exhalation valves, an appropriate nebulizer position should be carefully chosen, and the inhaled dose should be adjusted after accurate prediction of aerosol delivery to ensure optimal clinical efficacy.