Value of indomethacin suppository for preoperative analgesia and anti-inflammation in laparoscopic appendectomy: a protocol of prospective, double-blinded, single-centre, randomised controlled trial in China.

INTRODUCTION: Postoperative pain has always been a problem for patients and surgeons. Local inflammation, surgical trauma and pain in the body can cause a systemic stress response and immune imbalance, which can affect the patient's rapid recovery. Currently, most of the perioperative pain management is focused on the postoperative phase. The non-steroidal anti-inflammatory drug indomethacin suppository has antipyretic and analgesic effects. This study will evaluate the value of indomethacin suppository for analgesia and anti-inflammation before laparoscopic appendectomy (LA). METHODS AND ANALYSIS: A single-centre, double-blinded (clinician, assessor, data entry), randomised controlled trial will be conducted in 128 adult patients undergoing LA under emergency general anaesthesia with a Visual Analogue Scale (VAS) >2. The trial was divided into two groups (n=64) using a randomised number table: group A will be given 100 mg of indomethacin suppository rectally and group B will be given 8 mg of intravenous lornoxicam. The postoperative analgesic effect, inflammatory response and incidence of postoperative adverse effects will be compared. ETHICS AND DISSEMINATION: The study is in accordance with the Declaration of Helsinki and will be conducted in accordance with the principles of Good Clinical Practice. This trial was approved by the Ethics Committee of Beijing Luhe Hospital, Capital Medical University (2021-LHKY-123-02). We will disseminate our study findings at national and international paediatric research conferences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200062004).

Predictive Value of Perioperative Cardiac Troponin I in Patients Undergone Liver Transplantation: A Retrospective Cohort Study.

Objective: To examine the change rule and clinical significance of cardiac troponin I (cTnI) in the perioperative period of liver transplantation in adults, as well as its association with 28-day mortality. Methods: This was a retrospective cohort study: patients who underwent elective orthotopic liver transplantation (OLT) in Beijing Chao-Yang Hospital between June 2015 and June 2020 were selected, and plasma cTnI values were collected through the electronic medical record system within 7 days after surgery. Furthermore, the baseline clinical data of these patients were collected, and the change curve of cTnI values following liver transplantation was plotted. Using univariate and multivariate logistic regression models, the relationship between the level of postoperative cTnI and short-term mortality was investigated. The primary study endpoint was mortality within 28 days after surgery. Results: We included 414 patients who had undergone liver transplantation in this study, 48 of whom died within 28 days after surgery. cTnI, a specific marker of myocardial injury, could predict that the postoperative cardiovascular complications were higher in the death group and significantly affect the short-term prognosis of patients; however, its prognostic cut-off value was approximately 0.545 ng/mL (13×URL), indicating that a minor elevation of cTnI after liver transplantation did not significantly affect the prognosis. Moreover, a comparison of the baseline data and postoperative ICU management scores of the two groups revealed that diabetes, maximum value of cTnI >0.545 ng/mL within 7 days, and the need for postoperative renal replacement therapy (RRT) were independent prognostic factors of death within 28 days after liver transplantation. Conclusion: Within 7 days after surgery, an increase in cTnI to the maximum value of 0.545 ng/mL (13×URL) could have a significant impact on the short-term prognosis of patients. Diabetes and postoperative RRT were two independent prognostic factors for liver transplantation perioperative mortality.

Analysis of urinary C-C motif chemokine ligand 14 (CCL14) and first-generation urinary biomarkers for predicting renal recovery from acute kidney injury: a prospective exploratory study.

BACKGROUND: Acute kidney injury (AKI) is a frequent syndrome in the intensive care unit (ICU). AKI patients with kidney function recovery have better short-term and long-term prognoses compared with those with non-recovery. Numerous studies focus on biomarkers to distinguish them. To better understand the predictive performance of urinary biomarkers of renal recovery in patients with AKI, we evaluated C-C motif chemokine ligand 14 (CCL14) and two first-generation biomarkers (cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin) in two ICU settings. METHODS: We performed a prospective study to analyze urinary biomarkers for predicting renal recovery from AKI. Patients who developed AKI after ICU admission were enrolled and urinary biomarkers including tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), CCL14, and neutrophil gelatinase-associated lipocalin (NGAL) were detected on the day of AKI diagnosis. The primary endpoint was non-recovery from AKI within 7 days. The individual discriminative ability of CCL14, [TIMP-2] × [IGFBP7] and NGAL to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC). RESULTS: Of 164 AKI patients, 64 (39.0%) failed to recover from AKI onset. CCL14 showed a fair prediction ability for renal non-recovery with an AUC of 0.71 (95% CI 0.63-0.77, p < 0.001). [TIMP-2] × [IGFBP7] showed the best prediction for renal non-recovery with an AUC of 0.78 (95% CI 0.71-0.84, p < 0.001). However, NGAL had no use in predicting non-recovery with an AUC of 0.53 (95% CI 0.45-0.60, p = 0.562). A two-parameter model (non-renal SOFA score and AKI stage) predicted renal non-recovery with an AUC of 0.77 (95% CI 0.77-0.83, p = 0.004). When [TIMP-2] × [IGFBP7] was combined with the clinical factors, the AUC was significantly improved to 0.82 (95% CI 0.74-0.87, p = 0.049). CONCLUSIONS: Urinary CCL14 and [TIMP-2] × [IGFBP7] were fair predictors of renal non-recovery from AKI. Combing urinary [TIMP-2] × [IGFBP7] with a clinical model consisting of non-renal SOFA score and AKI stage enhanced the predictive power for renal non-recovery. Urinary CCL14 showed no significant advantage in predicting renal non-recovery compared to [TIMP-2] × [IGFBP7].

An inquiry into the treatment of sepsis using plasma exchange therapy: A systematic review and meta-analysis.

Sepsis is a potentially lethal condition that occurs when the body's response to infection damages tissue and organs. The production of inflammatory mediators typically assists in defending the body against infection; however, an overreaction to inflammation can cause coagulation problems, vascular endothelial damage, and organ hypoperfusion. Blood purification methods, such as plasmapheresis, can effectively remove inflammatory mediators from plasma. The purpose of this meta-analysis was to explore the efficacy of plasma exchange for sepsis treatment as noted in recent studies. The authors searched the Pubmed (Medline), Cochrane Central Register of Controlled Trials (The Cochrane Library), Embase (Ovid), and Scopus databases and included controlled clinical studies that compared plasmapheresis or plasma filtration with conventional treatment in patients with severe sepsis. The Newcastle-Ottawa Scale literature quality assessment tool was used to assess the risk of bias. The primary study outcome was all-cause mortality. The random effects model was adopted for conducting the meta-analysis. Among the 1013 records found, the study included 5 trials, all of which carried a low risk of bias. The use of plasmapheresis was associated with a longer stay in the intensive care unit (odds ratio [OR], 0.85, 95% confidence interval [CI], 0.39-1.32, heterogeneity [I2 ] = 0%), a significant reduction in all-cause mortality (OR, 0.54, 95% CI, 0.33-0.89, I2  = 70%), and reduced mortality (OR, 0.29, 95% CI, 0.13-0.67, I2  = 0%) in adults; the results for children differed from this (OR, 0.79, 95% CI, 0.36-1.72, I2  = 89%). Four trials reported no adverse events; one trial reported an adverse event related to plasma exchange, including an instance of hypotension in one patient. Plasmapheresis appeared to be an effective treatment for patients suffering from sepsis. A large number of additional randomised controlled trials are needed to confirm this finding.

Sequential treatment of severe pneumonia with respiratory failure and its influence on respiratory mechanical parameters and hemodynamics.

BACKGROUND: The pathophysiological characteristics of severe pneumonia complicated by respiratory failure comprise pulmonary parenchymal changes leading to ventilation imbalance, alveolar capillary injury, pulmonary edema, refractory hypoxemia, and reduced lung compliance. Prolonged hypoxia can cause acid-base balance disorder, peripheral circulatory failure, blood-pressure reduction, arrhythmia, and other adverse consequences. AIM: To investigate sequential mechanical ventilation's effect on severe pneumonia complicated by respiratory failure. METHODS: We selected 108 patients with severe pneumonia complicated by respiratory failure who underwent mechanical ventilation between January 2018 and September 2020 at the Luhe Hospital's Intensive Care Unit and divided them into sequential and regular groups according to a randomized trial, with each group comprising 54 patients. The sequential group received invasive and non-invasive sequential mechanical ventilation, whereas the regular group received invasive mechanical ventilation. Blood-gas parameters, hemodynamic parameters, respiratory mechanical parameters, inflammatory factors, and treatment outcomes were compared between the two groups before and after mechanical-ventilation treatment. RESULTS: The arterial oxygen partial pressure and stroke volume variation values of the sequential group at 24, 48, and 72 h of treatment were higher than those of the conventional group (P < 0.05). The carbon dioxide partial pressure value of the sequential group at 72 h of treatment and the Raw value of the treatment group at 24 and 48 h were lower than those of the conventional group (P < 0.05). The pH value of the sequential group at 24 and 72 h of treatment, the central venous pressure value of the treatment at 24 h, and the Cst value of the treatment at 24 and 48 h were higher than those of the conventional group (P < 0.05). The tidal volume in the sequential group at 24 h of treatment was higher than that in the conventional group (P < 0.05), the measured values of interleukin-6 and tumor necrosis factor-α in the sequential group at 72 h of treatment were lower than those in the conventional group (P < 0.05), and the total time of mechanical ventilation in the sequential group was shorter than that in the conventional group, with a statistically significant difference (P < 0.05). CONCLUSION: Treating severe pneumonia complicated by respiratory failure with sequential mechanical ventilation is more effective in improving respiratory system compliance, reducing inflammatory response, maintaining hemodynamic stability, and improving patient blood-gas levels; however, from this study's perspective, it cannot reduce patient mortality.

Tp-Te Interval and Tp-Te/QT Ratio Are Valuable Tools in Predicting Poor Outcome in Sepsis Patients.

Objective: About 50% of patients with sepsis have different degrees of myocardial inhibition, known as sepsis-induced myocardial dysfunction (SMD), which increases the mortality rate of sepsis. Tp-Te interval and Tp-Te/QT ratio reflect ventricular transmural dispersion repolarization (TDR), and have good predictive value for death in patients with heart disease. This study aimed to investigate the prognostic value of Tp-Te and Tp-Te/QT in patients with sepsis. Methods: The current study included a total of 625 participants: 201 patients with sepsis, 213 patients with heart failure, and 211 healthy participants. According to the severity and outcome, the patients with sepsis were divided into the sepsis group and the septic shock group, and the death group and the survival group to explore the differences of indicators among subgroups of sepsis. The ROC curve was used to analyze the predictive value of the indicators for deaths of patients with sepsis and calculate the cutoff point. Then, we investigated the incidence of arrhythmia in patients with sepsis with different TDR. The correlation between Tp-Te/QT and the commonly used predictive indicators in ICU was also discussed. Results: (1) Tp-Te and Tp-Te/QT in patients with sepsis and heart failure (HF) were significantly higher than the control group (p < 0.01). (2) Compared with patients with sepsis, the increase of Tp-Te and Tp-Te/QT is more prominent in patients with HF. Especially, the increase of the Tp-Te/QT was statistically significant (p < 0.001). (3) compared with patients with sepsis (no shock), the Tp-Te, Tp-Te/QT, and SOFA were increased in patients with septic shock (p < 0.05). (4) In the death group, Tp-Te /QT, SOFA, and Apache-II were higher; LVEF was lower than the survival group (p < 0.05). (5) ROC curves showed that Tp-Te/QT, SOFA, and LVEF have predictive values for death (p < 0.05; AUC = 0.808, 0.716, 0.412). The cutoff point of Tp-Te/QT was 0.32. (6) The incidence of arrhythmia is different in patients with sepsis with different TDR. (7) There is a significant correlation between Tp-Te/QT and SOFA (p < 0.001, r = 0.79). Conclusion: TDR in patients with sepsis is significantly increased, which was between healthy population and patients with HF. Tp-Te and Tp-Te/QT are effective indicators to reflect the severity and poor outcome of patients with sepsis.

Diagnostic value of ROC curve evaluation of serum markers in acute cholecystitis with bacterial infection.

OBJECTIVE: To explore correlation of serum markers human neutrophil lipocalin and C-reactive protein with acute cholecystitis associated with bacterial infection, and to evaluate the diagnostic value of the markers. METHODS: The cross-sectional study was conducted from January 2018 to April 2020 at the Beijing Luhe Hospital, Capital Medical University, Beijing, China, and comprised acute cholecystitis patients who were divided into bacterial infection group A and non-bacterial infection group B. Serum human neutrophil lipocalin and C-reactive protein were measured for both the groups. Receiver operating characteristic curve was used to evaluate the diagnostic value of the two markers in acute cholecystitis associated with bacterial infection. Data was analysed using SPSS 25. RESULTS: Of the 145 patients, 65(45%) were in group A; 36(55.38%) males and 29(44.62%) females with a mean age of 45.79±2.50 years. In group B there were 80(55%) subjects; 45(56.25%) males and 35(43.75%) females with a mean age of 46.16±2.52 years (p>0.05). In group A, there were 60(92.31%) cases of acute calculous cholecystitis, and 5(7.69%) had acute acalculous cholecystitis compared to 73(91.25%) and 7(8.75%), respectively, in group B (p>0.05). Serum human neutrophil lipocalin and C-reactive protein levels in group A were higher than group B (p<0.001). Serum human neutrophil lipocalin showed a high positive correlation with C-reactive protein in group A (r=0.800, p<0.001), and a moderate positive correlation in group B (r=0.683, p<0.001). Area under the curve of serum human neutrophil lipocalin associated with C-reactive protein was 0.901 (95% confidence interval: 0.850-0.953), which was higher than that of serum human neutrophil lipocalin and C-reactive protein alone, with sensitivity 95.40% and specificity 80%. CONCLUSIONS: The combined use of serum human neutrophil lipocalin and C-reactive protein may be used as an effective indicator for early diagnosis, identification and monitoring of acute cholecystitis with bacterial infection.

Cell cycle arrest biomarkers for predicting renal recovery from acute kidney injury: a prospective validation study.

BACKGROUND: Acute kidney injury (AKI) is a common disease in the intensive care unit (ICU). AKI patients with nonrecovery of renal function have a markedly increased risk of death compared with patients with recovery. The current study aimed to explore and validate the utility of urinary cell cycle arrest biomarkers for predicting nonrecovery in patients who developed AKI after ICU admission. METHODS: We prospectively and consecutively enrolled 379 critically ill patients who developed AKI after admission to the ICU, which were divided into a derivation cohort (194 AKI patients) and a validation cohort (185 AKI patients). The biomarkers of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were detected at inclusion immediately after AKI diagnosis (day 0) and 24 h later (day 1). The optimal cut-off values of these biomarkers for predicting nonrecovery were estimated in the derivation cohort, and their predictive accuracy was assessed in the validation cohort. The primary endpoint was nonrecovery from AKI (within 7 days). RESULTS: Of 379 patients, 159 (41.9%) patients failed to recover from AKI onset, with 79 in the derivation cohort and 80 in the validation cohort. Urinary [TIMP-2]*[IGFBP7] on day 0 showed a better prediction ability for nonrecovery than TIMP-2 and IGFBP7 alone, with an area under the reciever operating characteristic curve (AUC) of 0.751 [95% confidence interval (CI) 0.701-0.852, p < 0.001] and an optimal cut-off value of 1.05 ((ng/mL)2/1000). When [TIMP-2]*[IGFBP7] was combined with the clinical factors of AKI diagnosed by the urine output (UO) criteria, AKI stage 2-3 and nonrenal SOFA score for predicting nonrecovery, the AUC was significantly improved to 0.852 (95% CI 0.750-0.891, p < 0.001), which achieved a sensitivity and specificity of 88.8% (72.9, 98.7) and 92.6% (80.8, 100.0), respectively. However, urine [TIMP-2]*[IGFBP7], TIMP-2 alone, and IGFBP7 alone on day 1 performed poorly for predicting AKI recovery. CONCLUSION: Urinary [TIMP-2]*[IGFBP7] on day 0 showed a fair performance for predicting nonrecovery from AKI. The predictive accuracy can be improved when urinary [TIMP-2]*[IGFBP7] is combined with the clinical factors of AKI diagnosed by the UO criteria, AKI stage 2-3 and nonrenal SOFA score.

The Application of Electrical Impedance Tomography During the Ventilator Weaning Process.

BACKGROUND: This study proposes the investigation of electrical impedance tomography (EIT) as a useful predictor for ventilator weaning. METHODS: The study design was a nested case-control study and patients who were admitted to the intensive care unit and underwent their first tracheal intubation were enrolled. Those who successfully completed ventilator weaning and extubation after the first spontaneous breathing trial (SBT) were included in the weaning success group, while those who did not pass the SBT or received secondary intubation within 48 hours were included in the weaning failure group. In both groups, EIT was adopted to record the monitoring data in three phases: before the SBT (pre-SBT), during the SBT (SBT), and after the SBT (post-SBT). RESULTS: A total of 53 patients were enrolled, including 41 cases in the weaning success group and 12 cases in the weaning failure group. The logistic regression analysis showed that the pre-SBT global impedance (GI) and the SBT region of interest 2 (ROI2) were significantly higher in the weaning success group than in the weaning failure group (p = 0.0001 and p = 0.002). The pre-SBT GI predicted weaning success with a sensitivity of 0.524, a specificity of 0.818, a p-value of 0.0496, and a 95% confidence interval (CI) of 0.001-0.978. The sensitivity, specificity, p-value, and 95% CI for the SBT ROI2 were 1, 0.595, 0.0164, and 1.010-1.108, respectively. CONCLUSION: For patients without contraindications to EIT, the application of EIT is recommended to be added to the existing evaluation system for ventilator weaning, as it could help improve the weaning success rate. Further cohort studies are needed to investigate the actual efficacy of EIT after it has been added to the evaluation system.

Anti-Septic Potential of 7-α-Obacunyl Acetate Isolated from the Toona sinensis on Cecal Ligation/Puncture Mice via Suppression of JAK-STAT/NF-κB Signal Pathway.

PURPOSE: Sepsis is a life-threatening clinical syndrome and characterized by an inflammatory and innate immune response to infections. The current study was aimed to evaluate the anti-sepsis effect of 7-α-Obacunyl acetate (7-OBA), the abundant constituent isolated from Toona sinensis (Meliaceae), in cecal ligation and puncture (CLP)-induced mice and to investigate the related molecular mechanisms. METHODS: The CLP operation was performed to establish the sepsis mice model, and the survival rate and temperature were measured after 7-OBA treatment (7.5, 15, and 30 mg/kg; i.p.). Inflammatory cytokines levels of TNF-α, IL-1ß, IL-6, and IL-10 were detected by ELISA kits, and the kidney, liver, and heart function were measured using an automatic biochemistry analyzer. Effects of 7-OBA on NF-κB and JAK2-STAT3 signaling pathways were determined by Western blot analysis in a lipopolysaccharide (LPS) stimulated RAW264.7 cells model. RESULTS: 7-OBA treatment significantly increased the survival rate (p<0.05 and p<0.01) and normalized temperature (p<0.05 and p<0.01) of sepsis mice. The levels of pro-inflammatory cytokines like TNF-α, IL-1ß, and IL-6 in serum were obviously decreased, whereas the anti-inflammatory cytokines of IL-10 were increased. CLP-induced increases of the main markers of kidney, liver, and heart function in mice (p<0.01) were also obviously reversed by 7-OBA. The anti-sepsis effect of 7-OBA might be associated with regulation of nuclear factor kappa-B (NF-κB) and Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signal pathways. CONCLUSION: Our investigation indicated that 7-OBA can be developed as an effective agent for treating/curing sepsis in the future.

Granulocyte-Macrophage Colony-Stimulating Factor Inhalation Therapy for Severe Pulmonary Alveolar Proteinosis.

BACKGROUND: Some patients with pulmonary alveolar proteinosis (PAP) still present with high recurrence rate after large-volume whole lung lavage (WLL). Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been proved to be effective for PAP, but clinical research on GM-CSF inhalation therapy combined with WLL for severe PAP is rare in Asia. STUDY QUESTION: This study aimed to investigate the clinical efficacy of GM-CSF inhalation combined with WLL in Chinese patients with PAP. STUDY DESIGN: We performed regression analysis on 33 patients with severe PAP who underwent WLL alone or WLL combined with GM-CSF inhalation. The patients were put into 2 groups, WLL group and GM-CSF/WLL group. MEASURES AND OUTCOMES: Physiologic, serologic, and radiologic features of the 2 groups at different time points after treatment and the recurrence rates at 1-year follow-up were compared. RESULTS: There were no significant differences in lung function, blood gas analysis indices, and lung CT between the 2 groups after 1-week treatment (P > 0.05). After 3-month treatment, the GM-CSF/WLL group showed significantly faster improvement in FEV1%Pred (P = 0.028), FVC%Pred (P = 0.014), PaO2 (P = 0.022), PA-aO2 (P = 0.009), PaO2/FiO2 (P = 0.025), 6-minute walking test (P = 0.002), and lung CT parameters (P < 0.05) compared with the WLL group. The recurrence rate at the 1-year follow-up in the GM-CSF/WLL group (5.5%) was significantly higher than that in the WLL group (46.67%; P < 0.05). CONCLUSIONS: GM-CSF inhalation therapy combined with WLL is an effective treatment for patients with severe PAP, with further improvement in lung function at the base of WILL as well as reduction on re-WLL incidence.

A study on the protective effects of CpG oligodeoxynucleotide-induced mucosal immunity against lung injury in a mouse acute respiratory distress syndrome model.

This study aims to determine the feasibility of using oligodeoxynucleotides with unmethylated cytosine-guanine dinucleotide sequences (CpG ODN) as an immunity protection strategy for a mouse model of acute respiratory distress syndrome (ARDS). This is a prospective laboratory animal investigation. Twenty-week-old BALB/c mice in Animal research laboratory were randomized into groups. An ARDS model was induced in mice using lipopolysaccharides (LPSs). CpG ODN was intranasally and transrectally immunized before or after the 3rd and 7th days of establishing the ARDS model. Mice were euthanized on Day 7 after the second immunization. Then, retroorbital bleeding was carried out and the chest was rapidly opened to collect the trachea and tissues from both lungs for testing. CpG ODN significantly improved the pathologic impairment in mice lung, especially after the intranasal administration of 50 µg. This resulted in the least severe lung tissue injury. Furthermore, interleukin-6 (IL-6) and IL-8 concentrations were lower, which was second to mice treated with the rectal administration of 20 µg CpG ODN. In contrast, the nasal and rectal administration of CpG ODN in BALB/c mice before LPS immunization did not appear to exhibit any significant protective effects. The intranasal administration of CpG ODN may be a potential treatment approach to ARDS. More studies are needed to further determine the protective mechanism of CpG ODN.

Clinical emergency treatment of 68 critical patients with severe organophosphorus poisoning and prognosis analysis after rescue.

This study reports the clinical emergency treatment of 68 critical patients with severe organophosphorus poisoning, and analyzes the prognosis after rescue.The general data of 68 patients with severe organophosphorus poisoning treated in our hospital were retrospectively analyzed. These patients were divided into 2 groups: treatment group, and control group. Patients in the control group received routine emergency treatment, while patients in the treatment group additionally received hemoperfusion plus hemodialysis on the basis of routine emergency treatment. The curative effects in these 2 groups and the prognosis after rescue were compared.Compared with the control group, atropinization time, recovery time of cholinesterase activity, recovery time of consciousness, extubation time, and length of hospital stay were shorter (P < .05); the total usage of atropine was significantly lower (P < .05); Glasgow Coma Score was significantly higher (P < .05); acute physiology and chronic health score (APACHE II) was significantly lower (P < .05); and mortality and poisoning rebound rate was significantly lower (P < .05) in the treatment group.Hemoperfusion and hemodialysis on the basis of routine emergency treatment for critical patients with organophosphorus poisoning can improve rescue outcomes and improve the prognosis of patients, which should be popularized.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China.

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.

The Engrailed-1 Gene Stimulates Brown Adipogenesis.

As a thermogenic organ, brown adipose tissue (BAT) has received a great attention in treating obesity and related diseases. It has been reported that brown adipocyte was derived from engrailed-1 (EN1) positive central dermomyotome. However, functions of EN1 in brown adipogenesis are largely unknown. Here we demonstrated that EN1 overexpression increased while EN1 knockdown decreased lipid accumulation and the expressions of key adipogenic genes including PPARγ2 and C/EBPα and mitochondrial OXPHOS as well as BAT specific marker UCP1. Taken together, our findings clearly indicate that EN1 is a positive regulator of brown adipogenesis.

Correlation between different Chinese medicine syndromes and changes in microcirculation in septic shock patients.

OBJECTIVE: To investigate the correlation between different Chinese medicine (CM) syndromes and variations in microcirculation in septic shock patients. METHODS: seventy Septic shock patients were divided into four groups: heat damaging qi-yin group (HDQY, 23 cases); yin exhaustion and yang collapse group (YEYC, 26 cases); excessive heat in Fu organ group (EHFO, 10 cases); and heat damaging nutrient-blood group (HDNB, 11 cases). Sublingual microcirculation parameters were observed by sidestream dark-field (SDF) imaging and scored by Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA), and parameters of microcirculation perfusion variations and prognoses were analyzed. RESULTS: Compared with those with qi-yin heat damage, perfused vessel density (PVD) in other groups decreased dramatically (P<0.05), and APACHE II scores increased significantly (P<0.05). In addition, the recovery time was prolonged substantially (P<0.05), and the mixed venous oxygen saturation (SVO2) decreased (P<0.05). Blood lactic acid increased significantly (P<0.05), and the mixed SVO decreased (P<0.05), in the YEYC group. Compared with the thermal injury camp blood group, sublingual microcirculation parameter variations showed no obvious difference in the YEYC and EHFO groups (P>0.05). There were significant positive correlations between CM syndromes and APACHE II scoring in different groups (r=0.512, P<0.05). There were negative correlations between PVD and APACHE II scoring (r=-0.378, P=0.043), the proportion of perfused vessels (PPV) and APACHE II scoring (r=-0.472, P=0.008), as well as between the microvascular flow index (MFI) and APACHE II scoring (r=-0.424, P=0.023) in different patients. CONCLUSION: Sublingual microcirculation may serve as a clinical diagnostic parameter of the patient condition, as well as being a prognostic indicator.

[The clinical significance of determining the severity and prognosis by monitoring the changes in sublingual microcirculation in patients with severe sepsis].

OBJECTIVE: To investigate the clinical significance of dynamic monitoring of changes in the sublingual microcirculation in patients with severe sepsis to determine the degree of severity of the clinical condition and prognosis. METHODS: A prospective study was conducted. Sixty--five patients in the intensive care unit (ICU) in Beijing Friendship Hospital were enrolled from June 2010 to December 2010, among whom there were 30 cases of sepsis, 35 cases of severe sepsis. The severe sepsis patients received the early goal--directed resuscitation; and at 0 (before treatment), 6, 12, 24, 48, 72 hours after resuscitation, the technology of sidestream dark--field was used to measure the sublingual total vessel density (TVD), perfusing vessel density (PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) of sublingual microcirculation in patients and acute physiology and chronic health evaluation II (APACHEII) score, ICU days and 28--day mortality were recorded. Thirty healthy individuals were enrolled as the control group. RESULTS: The sublingual PPV and MFI were significantly lower in sepsis patients than those of the control group [PPV: (73.60 ± 16.77)% vs. (85.17 ± 7.60)%; MFI: 3.23 ± 0.77 vs. 3.78 ± 0.35, both P < 0.05]; PVD, PPV, MFI in severe sepsis patients were not only significantly lower than those of the sepsis group {PVD[mm/mm²]: 7.53 ± 4.38 vs.12.15 ± 2.88; PPV: (49.13 ± 33.74)% vs. (73.60 ± 16.77)%; MFI: 2.21 ± 1.41 vs. 3.23 ± 0.77, all P < 0.05}. After the early goal--directed fluid resuscitation, the sublingual microcirculation was improved significantly compared with that before treatment (0 hour), and they were remarkably apparent at 12 hours {TVD[mm/mm²]: 5.76 ± 2.25 vs. 6.72 ± 4.37; PVD [mm/mm²]: 7.57 ± 1.77 vs. 5.48 ± 4.39; PPV:(69.47 ± 19.24)% vs. (34.55 ± 30.82)%; MFI: 3.17 ± 0.49 vs. 1.55 ± 1.14, all P < 0.05}. Compared with the sepsis group, APACHEII score of the severe sepsis group was elevated (24.77 ± 7.45 vs. 19.30 ± 10.36, but P>0.05), the length of stay in ICU (days) was longer (20.60 ± 19.87 vs. 10.33 ± 9.53, P < 0.05), and the 28--day mortality was higher (45.71% vs. 36.36%, but P>0.05). In the severe sepsis group, compared with the survival group (19 cases), the sublingual microcirculation in the non-survival group (16 cases) PVD, PPV, MFI were significantly decreased{PVD[mm/mm²]:6.70 ± 5.15 vs. 8.53 ± 3.13; PPV: (44.23 ± 37.71)% vs. (54.96 ± 28.41)%; MFI: 1.89 ± 1.65 vs. 2.58 ± 0.98, P < 0.05 or P < 0.01}, but APACHEII score and length of stay in ICU (days) were not significantly different (23.19 ± 6.46 vs. 20.31 ± 6.03; 16.13 ± 10.90 vs. 19.19 ± 9.90, both P > 0.05). Correlation analysis showed that: PPV showed a significant negative correlation with the prognosis of the patients (r = -0.374, P < 0.05). CONCLUSION: Sequential monitoring of the sublingual microcirculation in patients with severe sepsis can be used to determine the disease severity, and to forecast the outcome of the patient.

Changes in intestinal mucosal immune barrier in rats with endotoxemia.

AIM: To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS: Male Wistar rats were randomly distributed into two groups: control group and lipopolysaccharide (LPS) group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold (M)-cells, dendritic cells (DCs), CD4(+) T cells, CD8(+) T cells, regulatory T (Tr) cells and IgA(+) B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin (IL)-4, interferon (IFN)-gamma and forkhead box P3 (Foxp3) in mucosal homogenates were measured by ELISA. The secretory IgA (sIgA) content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay. RESULTS: This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8(+) T cells, and IgA(+) B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4(+) T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-gamma increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased. CONCLUSION: Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunodeficiency.