Construction and validation of a nomogram for predicting survival in elderly patients with severe acute pancreatitis: a retrospective study from a tertiary center.

PURPOSE: There is a lack of adequate models specifically designed for elderly patients with severe acute pancreatitis (SAP) to predict the risk of death. This study aimed to develop a nomogram for predicting the overall survival of SAP in elderly patients. METHODS: Elderly patients diagnosed with SAP between January 1, 2017 and December 31, 2022 were included in the study. Risk factors were identified through least absolute shrinkage and selection operator regression analysis. Subsequently, a novel nomogram model was developed using multivariable logistic regression analysis. The predictive performance of the nomogram was evaluated using metrics such as the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: A total of 326 patients were included in the analysis, with 260 in the survival group and 66 in the deceased group. Multivariate logistic regression indicated that age, respiratory rate, arterial pH, total bilirubin, and calcium were independent prognostic factors for the survival of SAP patients. The nomogram demonstrated a performance comparable to sequential organ failure assessment (P = 0.065). Additionally, the calibration curve showed satisfactory predictive accuracy, and the DCA highlighted the clinical application value of the nomogram. CONCLUSION: We have identified key demographic and laboratory parameters that are associated with the survival of elderly patients with SAP. These parameters have been utilized to create a precise and user-friendly nomogram, which could be an effective and valuable clinical tool for clinicians.

High flow nasal cannula oxygen therapy versus non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease with acute-moderate hypercapnic respiratory failure: a randomized controlled non-inferiority trial.

BACKGROUND: Although cumulative studies have demonstrated a beneficial effect of high-flow nasal cannula oxygen (HFNC) in acute hypercapnic respiratory failure, randomized trials to compare HFNC with non-invasive ventilation (NIV) as initial treatment in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients with acute-moderate hypercapnic respiratory failure are limited. The aim of this randomized, open label, non-inferiority trial was to compare treatment failure rates between HFNC and NIV in such patients. METHODS: Patients diagnosed with AECOPD with a baseline arterial blood gas pH between 7.25 and 7.35 and PaCO2 ≥ 50 mmHg admitted to two intensive care units (ICUs) at a large tertiary academic teaching hospital between March 2018 and December 2022 were randomly assigned to HFNC or NIV. The primary endpoint was the rate of treatment failure, defined as endotracheal intubation or a switch to the other study treatment modality. Secondary endpoints were rates of intubation or treatment change, blood gas values, vital signs at one, 12, and 48 h, 28-day mortality, as well as ICU and hospital lengths of stay. RESULTS: 225 total patients (113 in the HFNC group and 112 in the NIV group) were included in the intention-to-treat analysis. The failure rate of the HFNC group was 25.7%, while the NIV group was 14.3%. The failure rate risk difference between the two groups was 11.38% (95% CI 0.25-21.20, P = 0.033), which was higher than the non-inferiority cut-off of 9%. In the per-protocol analysis, treatment failure occurred in 28 of 110 patients (25.5%) in the HFNC group and 15 of 109 patients (13.8%) in the NIV group (risk difference, 11.69%; 95% CI 0.48-22.60). The intubation rate in the HFNC group was higher than in the NIV group (14.2% vs 5.4%, P = 0.026). The treatment switch rate, ICU and hospital length of stay or 28-day mortality in the HFNC group were not statistically different from the NIV group (all P > 0.05). CONCLUSION: HFNC was not shown to be non-inferior to NIV and resulted in a higher incidence of treatment failure than NIV when used as the initial respiratory support for AECOPD patients with acute-moderate hypercapnic respiratory failure. TRIAL REGISTRATION: chictr.org (ChiCTR1800014553). Registered 21 January 2018, http://www.chictr.org.cn.

High-flow nasal cannula oxygen therapy for mild-moderate acute respiratory failure in patients with blunt chest trauma: An exploratory descriptive study.

OBJECTIVE: The use of high-flow nasal cannula (HFNC) oxygen therapy is gaining popularity for the treatment of acute respiratory failure (ARF). However, limited evidence exists regarding the effectiveness of HFNC for hypoxemic ARF in patients with blunt chest trauma (BCT). METHODS: This retrospective analysis focused on BCT patients with mild-moderate hypoxemic ARF who were treated with either HFNC or non-invasive ventilation (NIV) in the emergency medicine department from January 2021 to December 2022. The primary endpoint was treatment failure, defined as either invasive ventilation, or a switch to the other study treatment (NIV for patients in the NFNC group, and vice-versa). RESULTS: A total of 157 patients with BCT (72 in the HFNC group and 85 in the NIV group) were included in this study. The treatment failure rate in the HFNC group was 11.1% and 16.5% in the NIV group - risk difference of 5.36% (95% CI, -5.94-16.10%; P = 0.366). The most common cause of failure in the HFNC group was aggravation of respiratory distress. While in the NIV group, the most common reason for failure was treatment intolerance. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (1.4% vs 9.4%, 95% CI 0.40-16.18; P = 0.039). Univariate logistic regression analysis showed that chronic respiratory disease, abbreviated injury scale score (chest) (≥3), Acute Physiology and Chronic Health Evaluation II score (≥15), partial arterial oxygen tension /fraction of inspired oxygen (≤200) at 1 h of treatment and respiratory rate (≥32 /min) at 1 h of treatment were risk factors associated with HFNC failure. CONCLUSION: In BCT patients with mild-moderate hypoxemic ARF, the usage of HFNC did not lead to higher rate of treatment failure when compared to NIV. HFNC was found to offer better comfort and tolerance than NIV, suggesting it may be a promising new respiratory support therapy for BCT patients with mild-moderate ARF.

High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease patients after extubation: a multicenter, randomized controlled trial.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy is being increasingly used to prevent post-extubation hypoxemic respiratory failure and reintubation. However, evidence to support the use of HFNC in chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure after extubation is limited. This study was conducted to test if HFNC is non-inferior to non-invasive ventilation (NIV) in preventing post-extubation treatment failure in COPD patients previously intubated for hypercapnic respiratory failure. METHODS: COPD patients with hypercapnic respiratory failure who were already receiving invasive ventilation were randomized to HFNC or NIV at extubation at two large tertiary academic teaching hospitals. The primary endpoint was treatment failure, defined as either resumption of invasive ventilation or switching to the other study treatment modality (NIV for patients in the NFNC group or vice versa). RESULTS: Ninety-six patients were randomly assigned to the HFNC group or NIV group. After secondary exclusion, 44 patients in the HFNC group and 42 patients in the NIV group were included in the analysis. The treatment failure rate in the HFNC group was 22.7% and 28.6% in the NIV group-risk difference of - 5.8% (95% CI, - 23.8-12.4%, p = 0.535), which was significantly lower than the non-inferior margin of 9%. Analysis of the causes of treatment failure showed that treatment intolerance in the HFNC group was significantly lower than that in the NIV group, with a risk difference of - 50.0% (95% CI, - 74.6 to - 12.9%, p = 0.015). One hour after extubation, the mean respiratory rates of both groups were faster than their baseline levels before extubation (p < 0.050). Twenty-four hours after extubation, the respiratory rate of the HFNC group had returned to baseline, but the NIV group was still higher than the baseline. Forty-eight hours after extubation, the respiratory rates of both groups were not significantly different from the baseline. The average number of daily airway care interventions in the NIV group was 7 (5-9.3), which was significantly higher than 6 (4-7) times in the HFNC group (p = 0.006). The comfort score and incidence of nasal and facial skin breakdown of the HFNC group was also significantly better than that of the NIV group [7 (6-8) vs 5 (4-7), P < 0.001] and [0 vs 9.6%, p = 0.027], respectively. CONCLUSION: Among COPD patients with severe hypercapnic respiratory failure who received invasive ventilation, the use of HFNC after extubation did not result in increased rates of treatment failure compared with NIV. HFNC also had better tolerance and comfort than NIV. TRIAL REGISTRATION: chictr.org ( ChiCTR1800018530 ). Registered on 22 September 2018, http://www.chictr.org.cn/usercenter.aspx.

Duration of cardiac arrest requires different ventilation volumes during cardiopulmonary resuscitation in a pig model.

There are few studies examining the ventilation strategies recommended by current CPR guidelines. We investigated the influence of different minute volume applying to untreated cardiac arrest with different duration, on resuscitation effects in a pig model. 32 Landrace pigs with 4 or 8 min (16 pigs each) ventricular fibrillation (VF) randomly received two ventilation strategies during CPR. "Guideline" groups received mechanical ventilation with a tidal volume of 7 ml/kg and a frequency of 10/min, while "Baseline" groups received a tidal volume (10 ml/kg) and a frequency used at baseline to maintain an end-tidal PCO2 (PETCO2) between 35 and 40 mmHg before VF. Mean airway pressures and intrathoracic pressures (PIT) in the Baseline-4 min group were significantly higher than those in the Guideline-4 min group (all P < 0.05). Similar results were observed in the 8 min pigs, except for no significant difference in minimal PIT and PETCO2 during 10 min of CPR. Venous pH and venous oxygen saturation were significantly higher in the Baseline-8 min group compared to the Guideline-8 min group (all P < 0.05). Aortic pressure in the Baseline-8 min group was higher than in the Guideline-8 min group. Seven pigs in each subgroup of 4 min VF models achieved the return of spontaneous circulation (ROSC). Higher ROSC was observed in the Baseline-8 min group than in the Guideline-8 min group (87.5% vs. 37.5%, P = 0.039). For 4 min VF but not 8 min VF, a guideline-recommended ventilation strategy had satisfactory results during CPR. A higher minute ventilation resulted in better outcomes for subjects with 8 min of untreated VF through thoracic pump.

[The effect of blood volume change on the accuracy of pulse contour cardiac output].

OBJECTIVE: To study the accuracy of pulse contour cardiac output (PCCO) during blood volume change. METHODS: Hemorrhagic shock model was made in twenty dogs followed by volume resuscitation. Two PiCCO catheters were placed into each model to monitor the cardiac output (CO). One of catheters was used to calibrate CO by transpulmonary thermodilution technique (COTP) (calibration group), and the other one was used to calibrate PCCO (none-calibration group). In the hemorrhage phase, calibration was carried out each time when the blood volume dropped by 5 percents in the calibration group until the hemorrhage volume reached to 40 percent of the basic blood volume. Continuous monitor was done in the none-calibration group.Volume resuscitation phase started after re-calibration in the two groups. Calibration was carried out each time when the blood equivalent rose by 5 percents in calibration group until the percentage of blood equivalent volume returned back to 100. Continuous monitor was done in none-calibration group. COTP, PCCO, mean arterial pressure (MAP), systemic circulation resistance (SVR), global enddiastolic volume (GEDV) were recorded respectively in each time point. RESULTS: (1) At the baseline, COTP in calibration group showed no statistic difference compared with PCCO in none-calibration group (P >0.05). (2) In the hemorrhage phase, COTP and GEDV in calibration group decreased gradually, and reached to the minimum value (1.06 ± 0.57) L/min, (238 ± 93) ml respectively at TH8. SVR in calibration group increased gradually, and reached to the maximum value (5 074 ± 2 342) dyn · s · cm⁻5 at TH6. However, PCCO and SVR in none-calibration group decreased in a fluctuating manner, and reached to the minimum value (2.42 ± 1.37) L/min, (2 285 ± 1 033) dyn · s · cm⁻5 respectively at TH8. COTP in the calibration group showed a significant statistic difference compared with PCCO in the none-calibration group at each time point (At TH1-8, t values were respectively -5.218, -5.495, -4.639, -6.588, -6.029, -5.510, -5.763 and -5.755, all P < 0.01). From TH1 to TH8, the difference in percentage increased gradually. There were statistic differences in SVR at each time point between the two groups (At TH1 and TH4, t values were respectively 2.866 and 2.429, both P < 0.05, at TH2 - TH3 and TH5 - TH8, t values were respectively 3.073, 3.590, 6.847, 8.425, 6.910 and 8.799, all P < 0.01). There was no statistic difference in MAP between the two groups (P > 0.05). (3) In the volume resuscitation phase, COTP and GEDV in the calibration group increased gradually. GEDV reached to the maximum value ((394±133) ml) at TR7, and COTP reached to the maximum value (3.15 ± 1.42) L/min at TR8. SVR in the calibration group decreased gradually, and reached to the minimum value (3 284 ± 1 271) dyn · s · cm⁻5 at TR8. However, PCCO and SVR in the none-calibration group increased in a fluctuating manner. SVR reached to the maximum value (8 589 ± 4 771) dyn · s · cm⁻5 at TR7, and PCCO reached to the maximum value (1.35 ± 0.70) L/min at TR8. COTP in the calibration group showed a significant statistic difference compared with PCCO in the none-calibration group at each time point (At TR1-8, t values were respectively 8.195, 8.703, 7.903, 8.266, 9.600, 8.340, 8.938, 8.332, all P < 0.01). From TR1 to TR8, the difference in percentage increased gradually. There were statistic differences in SVR at each time point between the two groups (At TR1, t value was -2.810, P < 0.05, at TR2-8, t values were respectively -6.026, -6.026, -5.375, -6.008, -5.406, -5.613 and -5.609, all P < 0.05). There was no statistic difference in MAP between the two groups (P > 0.05). CONCLUSION: PCCO could not reflect the real CO in case of rapid blood volume change, which resulting in the misjudgment of patient's condition. In clinical practice, more frequent calibrations should be done to maintain the accuracy of PCCO in rapid blood volume change cases.

Acute High-Output Heart Failure with Pulmonary Hypertension and Severe Liver Injury Caused by Amlodipine Poisoning: A Case Report.

Acute high-output heart failure (HOHF) with pulmonary hypertension and liver injury caused by amlodipine poisoning is very rare. We report a 52-year-old woman who suffered from severe shock after an overdose of amlodipine. Hemodynamic monitoring showed that while her left ventricular systolic function and cardiac output were elevated, her systemic vascular resistance decreased significantly. At the same time, the size of her right heart, her central venous pressure, and the oxygen saturation of her central venous circulation all increased abnormally. The patient's circulatory function and right ventricular dysfunction gradually improved after large doses of vasopressors and detoxification measures. However, her bilirubin and transaminase levels increased significantly on hospital day 6, with a CT scan showing patchy, low-density areas in her liver along with ascites. After liver protective treatment and plasma exchange, the patient's liver function gradually recovered. A CT scan 4 months later showed all her liver abnormalities, including ascites, had resolved. The common etiologies of HOHF were excluded in this case, and significantly reduced systemic vascular resistance caused by amlodipine overdose was thought to be the primary pathophysiological basis of HOHF. The significant increase in venous return and pulmonary blood flow is considered to be the main mechanism of right ventricular dysfunction and pulmonary hypertension. Hypoxic hepatitis caused by a combination of hepatic congestion and distributive shock may be the most important factors causing liver injury in this patient. Whether amlodipine has other mechanisms leading to HOHF and pulmonary hypertension needs to be further studied. Considering the significant increase of right heart preload, aggressive fluid resuscitation should be done very cautiously in patients with HOHF and shock secondary to amlodipine overdose.

High-flow nasal cannula oxygen therapy is equally effective to noninvasive ventilation for mild-moderate acute respiratory distress syndrome in patients with acute pancreatitis: A single-center, retrospective cohort study.

BACKGROUND: The use of high-flow nasal cannula (HFNC) oxygen therapy is gaining popularity for the treatment of acute hypoxic respiratory failure. However, limited evidence exists regarding the effectiveness of HFNC for acute respiratory distress syndrome (ARDS) in patients with acute pancreatitis (AP). METHODS: This retrospective analysis focused on AP patients with mild-moderate ARDS, who were treated with either HFNC or noninvasive ventilation (NIV) in the emergency medicine department, from January 2020 to December 2022. The primary endpoint was treatment failure, defined as either invasive ventilation or a switch to any other study treatment (NIV for patients in the NFNC group and vice versa). RESULTS: A total of 146 patients with AP (68 in the HFNC group and 78 in the NIV group) were included in this study. The treatment failure rate in the HFNC group was 17.6% and 19.2% in the NIV group - a risk difference of -1.6% (95% CI, -11.3 to 14.0%; P = 0.806). The most common causes of failure in the HFNC group were aggravation of respiratory distress and hypoxemia. However, in the NIV group, the most common reasons for failure were treatment intolerance and exacerbation of respiratory distress. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (16.7% vs 60.0%, 95% CI -66.8 to -6.2; P = 0.023). Multivariate logistic regression analysis showed that body mass index (≥28), acute physiology and chronic health evaluation II score (≥15), partial arterial oxygen tension/fraction of inspired oxygen (≤200), and respiratory rate (≥32/min) at 1 hour were independent predictors of HFNC failure. CONCLUSION: In AP patients with mild-moderate ARDS, the usage of HFNC did not lead to a higher rate of treatment failure when compared to NIV. HFNC is an ideal choice of respiratory support for patients with NIV intolerance, but clinical application should pay attention to the influencing factors of its treatment failure.

Management of regional citrate anticoagulation for continuous renal replacement therapy: guideline recommendations from Chinese emergency medical doctor consensus.

Continuous renal replacement therapy (CRRT) is widely used for treating critically-ill patients in the emergency department in China. Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT. Regional citrate anticoagulation (RCA) has been shown to potentially be safer and more effective and is now recommended as the preferred anticoagulant method for CRRT. However, there is still a lack of unified standards for RCA management in the world, and there are many problems in using this method in clinical practice. The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association (CMDA) organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues, including the advantages and disadvantages of RCA in CRRT anticoagulation, the principle of RCA, parameter settings for RCA, monitoring of RCA (mainly metabolic acid-base disorders), and special issues during RCA. Based on the latest available research evidence as well as the paneled experts' clinical experience, considering the generalizability, suitability, and potential resource utilization, while also balancing clinical advantages and disadvantages, a total of 16 guideline recommendations were formed from the experts' consensus.

High-flow nasal cannula oxygen therapy versus noninvasive ventilation for patients with blunt chest trauma: protocol for a randomized controlled trial.

BACKGROUND: High-flow nasal cannula oxygen therapy (HFNC) is recommended by some scholars as an optimized respiratory support method for blunt chest trauma (BCT) patients. The basis of this recommendation is limited, however, and the efficacy of HFNC or noninvasive ventilation (NIV) in BCT patients has not yet been rigorously explored. This study aims to determine if HFNC is non-inferior to NIV in reducing treatment failure in moderate to severe BCT patients with acute respiratory failure. METHODS: This will be a prospective, open-label, multicenter, non-inferiority, randomized controlled trial. Moderate to severe BCT patients with acute respiratory failure (100mmHg < PaO2/FiO2 ≦ 200mmHg) who do not need immediate intubation will be randomized to HFNC or NIV within 48 h after trauma. The primary outcome is treatment failure, defined as invasive ventilation or a switch in respiratory support modality (from HFNC to NIV or vice-versa). Secondary outcomes include arterial blood gas analysis and vital signs at 2 and 12 h after initiating HFNC or NIV treatment, as well as patients' comfort scores, dyspnea scores, daily number of nursing airway care interventions, incidence of pneumonia or pneumothorax, facial skin breakdown, duration of NIV or HFNC, 28-day mortality, and total ICU and hospital lengths of stay. Based on an α error of 5% and a ß error of 80%, with a non-inferiority limit of 9%, a sample size of 562 will be required to accomplish the trial goal, considering potential patient dropouts and nonparametric analysis. DISCUSSION: We hypothesize that HFNC will be non-inferior to NIV in reducing treatment failure in moderate to severe BCT with acute respiratory failure. The results should be useful for judging whether HFNC could be an effective alternative to NIV to treat moderate to severe BCT patients, especially for those who do not tolerate or have contraindications for NIV. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800017313 . Registered on July 24, 2018.

A Nomogram Model for Predicting Type-2 Myocardial Infarction Induced by Acute Upper Gastrointestinal Bleeding.

OBJECTIVE: To examine the independent risk factors of type-2 myocardial infarction (T2MI) elicited by acute upper gastrointestinal bleeding (AUGIB), and to establish a nomogram model for the prediction of AUGIB-induced T2MI. METHODS: A nomogram model was established on the basis of a retrospective study that involved 533 patients who suffered from AUGIB in the Department of Critical Care Medicine (CCM) or Emergency Intensive Care Unit (EICU) of Renmin Hospital of Wuhan University, Wuhan, China, from January 2017 to December 2020. The predictive accuracy and discriminative power of the nomogram were initially evaluated by internal validation, which involved drawing the receiver operating characteristic (ROC) curve, calculating the area under the curve (AUC), plotting the calibration curve derived from 1000 resampled bootstrap data sets, and computing the root mean square error (RMSE). The predictive ability of the nomogram was further validated through the prospective and multicenter study conducted by the investigators, which enrolled 240 AUGIB patients [including 88 cases from Renmin Hospital of Wuhan University, 73 cases from Qilu Hospital of Shandong University (Qingdao), and 79 cases from Northern Jiangsu People's Hospital)], who were admitted to the Department of CCM or EICU, from February 2021 to July 2021. RESULTS: Among the 533 patients in the training cohort, 78 (14.6%) patients were assigned to the T2MI group and 455 (85.4%) patients were assigned to the non-T2MI group. The multivariate analysis revealed that age >65, hemorrhagic shock, cerebral stroke, heart failure, chronic kidney disease, increased blood urea nitrogen, decreased hematocrit, and elevated D-Dimer were independent risk factors for AUGIB-induced T2MI. All these factors were incorporated into the nomogram model. The AUC for the nomogram for predicting T2MI was 0.829 (95% CI, 0.783-0.875) in the internal validation cohort and 0.848 (95% CI, 0.794-0.902) in the external validation cohort. The calibration curve for the risk of T2MI exhibited good consistency between the prediction by the nomogram and the actual clinical observation in both the internal validation (RMSE=0.016) and external validation (RMSE=0.020). CONCLUSION: The nomogram was proven to be a useful tool for the risk stratification of T2MI in AUGIB patients, and is helpful for the early identification of AUGIB patients who are prone to T2MI for early intervention, especially in emergency departments and intensive care units.

Xuebijing Injection Ameliorates H2S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression.

OBJECTIVE: To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H2S)-induced acute respiratory distress syndrome (ARDS). METHODS: Sprague-Dawley rats were exposed to H2S (300 ppm) to establish ARDS model, while human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a H2S donor, 500 µmol/L) to establish cell model. H2S and XBJ were concurrently administered to the rat and cell models. Lung hematoxylin and eosin staining, immunohistochemistry, transmission electron microscopy and wet/dry ratio measurement were used to confirm ARDS induced by H2S in vivo. The expression levels of claudin-5, phosphorylated protein kinase B (p-AKT)/t-AKT and p-forkhead box transcription factor O1 (FoxO1)/t-FoxO1 in vivo and in vitro were also assessed. Paracellular permeability and transepithelial electrical resistance (TEER) were measured to evaluate endothelial barrier function in the cell model. RESULTS: The morphological investigation showed that XBJ attenuated H2S-induced ARDS in rats. XBJ significantly ameliorated both the reduction in TEER and the increased paracellular permeability observed in NaHS-treated HPMECs (P<0.05). The protective effects of XBJ were blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K)/AKT/FoxO1 pathway antagonist (P<0.05). Furthermore, XBJ promoted the expression of claudin-5 and increased the levels of p-AKT and p-FoxO1 in vivo and in vitro (P<0.05). CONCLUSIONS: XBJ ameliorated H2S-induced ARDS by promoting claudin-5 expression via the PI3K/AKT/FoxO1 signaling pathway.

Oxyberberine Prevented Lipopolysaccharide-Induced Acute Lung Injury through Inhibition of Mitophagy.

Acute lung injury (ALI) is a serious respiratory syndrome characterized with uncontrolled inflammatory response. Oxyberberine has strong potential for clinical usage since it showed strong anti-inflammatory, antifungal, and antiarrhythmic effects in various diseases. In the present study, we evaluated whether oxyberberine can inhibit lipopolysaccharide- (LPS-) induced ALI in vivo and further evaluated the possible involvement of mitophagy in vitro by using A549 cells, a human lung epithelial cell line. Our in vivo study shows that oxyberberine significantly inhibited LPS-induced lung pathological injury and lung edema, as indicated by the changes in lung wet/dry ratio and total protein levels in the BALF in mice. Moreover, oxyberberine inhibited inflammation, as indicated by the changes of neutrophil accumulation and production of proinflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6 in both the lung and bronchoalveolar lavage fluid (BALF) in ALI mice. Our in vitro study shows that LPS significantly decreased the protein level of mitochondrial proteins, including cytochrome c oxidase subunit IV (COX IV), p62, and mitofusin-2 (Mfn2) in A549 cells. In addition, LPS induced significant Parkin1 translocation from cytoplasm to mitochondria. These changes were significantly inhibited by oxyberberine. Notably, the inhibitory effect of oxyberberine was almost totally lost in the presence of lysosome fusion inhibitor bafilomycin A1 (Baf), a mitophagy inhibitor. In conclusion, the present study demonstrated that oxyberberine alleviated LPS-induced inflammation in ALI via inhibition of Parkin-mediated mitophagy.

Pulse oximetry waveform: A non-invasive physiological predictor for the return of spontaneous circulation in cardiac arrest patients ---- A multicenter, prospective observational study.

OBJECTIVE: This study aimed to investigate the predictive value of pulse oximetry plethysmography (POP) for the return of spontaneous circulation (ROSC) in cardiac arrest (CA) patients. METHODS: This was a multicenter, observational, prospective cohort study of patients hospitalized with cardiac arrest at 14 teaching hospitals cross China from December 2013 through November 2014. The study endpoint was ROSC, defined as the restoration of a palpable pulse and an autonomous cardiac rhythm lasting for at least 20 minutes after the completion or cessation of CPR. RESULTS: 150 out-of-hospital cardiac arrest (OHCA) patients and 291 in-hospital cardiac arrest (IHCA) patients were enrolled prospectively. ROSC was achieved in 20 (13.3%) and 64 (22.0%) patients in these cohorts, respectively. In patients with complete end-tidal carbon dioxide (ETCO2) and POP data, patients with ROSC had significantly higher levels of POP area under the curve (AUCp), wave amplitude (Amp) and ETCO2 level during CPR than those without ROSC (all p < 0.05). Pairwise comparison of receiver operating characteristic (ROC) curve analysis indicated no significant difference was observed between ETCO2 and Amp (p = 0.204) or AUCp (p = 0.588) during the first two minutes of resuscitation. CONCLUSION: POP may be a novel and effective method for predicting ROSC during resuscitation, with a prognostic value similar to ETCO2 at early stage.

Involvement of claudin-5 in H2S-induced acute lung injury.

Acute exposure to hydrogen sulfide (H2S) can cause fatal acute lung injury (ALI). However, the mechanisms of H2S-induced ALI are still not fully understood. This study aims to investigate the role of the tight junction protein claudin-5 in H2S-induced ALI. In our study, Sprague-Dawley (SD) rats were exposed to H2S to establish the ALI model, and in parallel, human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a H2S donor) to establish a cell model. Lung immunohistochemistry and electron microscopy assays were used to identify H2S-induced ALI, and the expression of claudin-5, p-AKT/t-AKT and p-FoxO1/t-FoxO1 was detected. Our results show that H2S promoted the formation of ALI by morphological investigation and decreased claudin-5 expression. Dexamethasone (Dex) could partly attenuate NaHS-mediated claudin-5 downregulation, and the protective effects of Dex could be partially blocked by LY294002, a PI3K/AKT/FoxO1 pathway antagonist. Moreover, as a consequence of the altered phosphorylation of AKT and FoxO1, a change in claudin-5 with the same trend was observed. Therefore, the tight junction protein claudin-5 might be considered a therapeutic target for the treatment of ALI induced by H2S and other hazardous gases.

[Xuebijing injection attenuates hydrogen sulfide-induced endothelial barrier dysfunction by upregulating claudin-5 expression].

OBJECTIVE: To study the new mechanism of Xuebijing injection improving the function of pulmonary vascular barrier from the perspective of claudin-5 protein. METHODS: Acute lung injury (ALI) model was induced by hydrogen sulfide (H2S) exposure. (1) In vivo study: Sprague-Dawley (SD) rats were divided into control group, H2S exposure group (exposure to 300×10-6 H2S for 3 hours), Xuebijing control group (Xuebijing injection 4 mL/kg , twice a day, for 3 days), and Xuebijing intervention group (H2S exposure after pretreatment of Xuebijing injection) according to random number method, with 6 rats in each group. At different time points (0, 6, 12 and 24 hours) after the model was made successfully, the total protein content in plasma and bronchoalveolar lavage fluid (BALF) of rats were detected respectively, and the pulmonary permeability index (PPI) was calculated (PPI = protein content in BALF/protein content in plasma), lung dry/wet weight ratio (W/D) was detected, and claudin-5 mRNA expression in lung tissue was measured by real time-polymerase chain reaction. (2) In vitro test: human pulmonary microvascular endothelial cells (HPMECs) were divided into blank control group, NaHS treatment group (co-incubated with 500 µmol/L NaHS for 12 hours), Xuebijing control group (2 g/L Xuebijing injection for 24 hours), and Xuebijing intervention group (2 g/L Xuebijing injection pre-treated for 24 hours, then co-incubated with 500 µmol/L NaHS for 12 hours). The HPMECs claudin-5 protein expression and monolayer permeability changes were measured at different co-incubation time (1, 3, 6, 12 and 24 hours) by Western Blot and fluoresceinsodium. RESULTS: (1) In vivo study: compared with the control group, the lung W/D ratio increased significantly at 6 hours and peaked at 12 hours after H2S exposure in rats (4.67±0.11 vs. 4.26±0.06, P < 0.01). The expression of claudin-5 mRNA in lung tissue was significantly decreased, which was 89% of control group 6 hours after exposure (P < 0.01). The total protein content in BALF and PPI at 12 hours after exposure were significantly higher than those in the control group [total protein content (mg/L): 262.31±14.24 vs. 33.30±3.09, PPI: (11.72±0.57)×10-3 vs. (1.21±0.08)×10-3, both P < 0.01], while the results in Xuebijing intervention group were significantly decreased [total protein content (mg/L): 153.25±7.32 vs. 262.31±14.24, PPI: (5.79±0.23)×10-3 vs. (11.72±0.57)×10-3, both P < 0.01]. (2) In vitro test: compared with the blank control group, after incubating HPMECs with NaHS, the permeability of monolayer endothelial cells gradually increased, reaching the highest level in 12 hours, about twice of that in the blank control group, while claudin-5 protein expression decreased to the lowest level at 12 hours (claudin-5/ß-actin: 0.42±0.03 vs. 1.03±0.05, P < 0.01). After intervention with Xuebijing, the permeability of endothelial cells was significantly improved (fluorescence intensity of fluorescein sodium: 1.46±0.10 vs. 1.89±0.11, P < 0.01), and the decrease of claudin-5 protein was reduced (claudin-5/ß-actin: 0.68±0.04 vs. 0.38±0.03, P < 0.01). CONCLUSIONS: Xuebijing injection may improve pulmonary vascular barrier function in ALI by upregulating claudin-5 expression.

A meta-analysis of early oral refeeding and quickly increased diet for patients with mild acute pancreatitis.

BACKGROUND/AIM: The objective of the study is to clarify whether early oral refeeding (EORF) and quickly increasing diet (QID) are of benefit to patients with mild acute pancreatitis compared with a traditional oral refeeding strategy. MATERIALS AND METHODS: Studies were searched in PubMed, Cochrane library, ScienceDirect, SpringerLink, China Biology Medicine disc and Embase. A meta-analysis was then performed, using relapse of abdominal pain, nausea/vomiting, and length of hospital stay (LOHS) as the evaluation indices. RESULTS: Eight trials met the inclusion criteria. For the oral refeeding time group, EORF could significantly decrease the LOHS (mean deviation [MD] -1.97; 95% confidence interval (CI) -3.32 to -0.62;P = 0.004), and there was no significant difference for relapse of abdominal pain (relative risk [RR] 1.17; 95% CI 0.69-2.00;P = 0.56) or nausea/vomiting (RR 1.30; 95% CI 0.19-8.82;P = 0.79) when compared with conventional oral refeeding. For the oral refeeding material group, there was no significant difference for relapse of abdominal pain (RR 0.86; 95% CI 0.53-1.40;P = 0.54), nausea/vomiting (risk difference -0.01; 95% CI -0.19-0.18;P = 0.94), or LOHS (MD -0.88; 95% CI -2.24-0.48;P = 0.20) between the QID and stepwise increasing diet groups. CONCLUSION: Pure EORF or QID caused no damage to patients with mild acute pancreatitis, and EORF could significantly decrease the LOHS.