Gut microbiota-derived nicotinamide mononucleotide alleviates acute pancreatitis by activating pancreatic SIRT3 signalling.

BACKGROUND AND PURPOSE: Gut microbiota dysbiosis induced by acute pancreatitis (AP) exacerbates pancreatic injury and systemic inflammatory responses. The alleviation of gut microbiota dysbiosis through faecal microbiota transplantation (FMT) is considered a potential strategy to reduce tissue damage and inflammation in many clinical disorders. Here, we aim to investigate the effect of gut microbiota and microbiota-derived metabolites on AP and further clarify the mechanisms associated with pancreatic damage and inflammation. EXPERIMENTAL APPROACH: AP rat and mouse models were established by administration of caerulein or sodium taurocholate in vivo. Pancreatic acinar cells were exposed to caerulein and lipopolysaccharide in vitro to simulate AP. KEY RESULTS: Normobiotic FMT alleviated AP-induced gut microbiota dysbiosis and ameliorated the severity of AP, including mitochondrial dysfunction, oxidative damage and inflammation. Normobiotic FMT induced higher levels of NAD+ (nicotinamide adenine dinucleotide)-associated metabolites, particularly nicotinamide mononucleotide (NMN). NMN administration mitigated AP-mediated mitochondrial dysfunction, oxidative damage and inflammation by increasing pancreatic NAD+ levels. Similarly, overexpression of the NAD+ -dependent mitochondrial deacetylase sirtuin 3 (SIRT3) alleviated the severity of AP. Furthermore, SIRT3 deacetylated peroxiredoxin 5 (PRDX5) and enhanced PRDX5 protein expression, thereby promoting its antioxidant and anti-inflammatory activities in AP. Importantly, normobiotic FMT-mediated NMN metabolism induced SIRT3-PRDX5 pathway activation during AP. CONCLUSION AND IMPLICATIONS: Gut microbiota-derived NMN alleviates the severity of AP by activating the SIRT3-PRDX5 pathway. Normobiotic FMT could be served as a potential strategy for AP treatment.

Cut-off values of lesion and vessel quantitative flow ratio in de novo coronary lesion post-drug-coated balloon therapy predicting vessel restenosis at mid-term follow-up.

BACKGROUND: Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up. METHODS: The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DS ≥50%, and group B, showing target vessel DS <50%. The median follow-up time was 287 days in group A and 227 days in group B. We compared the clinical characteristics, parameters during DCB therapy, and QFR performances, which were analyzed by CAG images between the two groups, in need to explore the cut-off value of lesion/vessel QFR which can predict vessel restenosis. Student's t test was used for the comparison of normally distributed continuous data, Mann-Whitney U test for the comparison of non-normally distributed continuous data, and receiver operating characteristic (ROC) curves for the evaluation of QFR performance which can predict vessel restenosis (DS ≥50%) at mid-term follow-up using the area under the curve (AUC). RESULTS: A total of 112 patients with 112 target vessels were enrolled in this study. Group A had 41 patients, while group B had 71. Vessel QFR and lesion QFR were lower in group A than in group B post-DCB therapy, and the cut-off values of lesion QFR and vessel QFR in the ROC analysis to predict target vessel DS ≥50% post-DCB therapy were 0.905 (AUC, 0.741 [95% confidence interval, CI: 0.645, 0.837]; sensitivity, 0.817; specificity, 0.561; P < 0.001) and 0.890 (AUC, 0.796 [95% CI: 0.709, 0.882]; sensitivity, 0.746; specificity, 0.780; P < 0.001). CONCLUSIONS: The cut-off values of lesion QFR and vessel QFR can assist in predicting the angiographic changes post-DCB therapy. When lesion/vessel QFR values are <0.905/0.890 post-DCB therapy, a higher risk of vessel restenosis is potentially predicted at follow-up.

The timing of continuous renal replacement therapy initiation in sepsis-associated acute kidney injury in the intensive care unit: the CRTSAKI Study (Continuous RRT Timing in Sepsis-associated AKI in ICU): study protocol for a multicentre, randomised controlled trial.

INTRODUCTION: Acute kidney injury (AKI) is one of the most common organ dysfunction in sepsis, and increases the risk of unfavourable outcomes. Renal replacement therapy (RRT) is the predominant treatment for sepsis-associated AKI (SAKI). However, to date, no prospective randomised study has adequately addressed whether initiating RRT earlier will attenuate renal injury and improve the outcome of sepsis. The objective of the trial is to compare the early strategy with delayed strategy on the outcomes in patients with SAKI in the intensive care unit (ICU). METHODS AND ANALYSIS: This is a large-scale, multicentre, randomised controlled trial about SAKI. In total, 460 patients with sepsis and evidence of AKI stage 2 of Kidney Disease Improving Global Outcomes (KDIGO) will be recruited and equally randomised into the early group and the delay group in a ratio of 1:1. In the early group, continuous RRT (CRRT) will be started immediately after randomisation. In the delay group, CRRT will initiated if at least one of the following criteria was met: stage 3 of KDIGO, severe hyperkalaemia, pulmonary oedema, blood urea nitrogen level higher than 112 mg/dL after randomisation. The primary outcome is overall survival in a 90-day follow-up period (90-day all-cause mortality). Other end points include 28-day, 60-day and 1-year mortality, recovery rate of renal function by day 28 and day 90, ICU and hospital length of stay, the numbers of CRRT-free days, mechanical ventilation-free days and vasopressor-free days, the rate of complications potentially related to CRRT, CRRT-related cost, and concentrations of inflammatory mediators in serum. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2017-31-ks-01). Participants will be screened and enrolled from patients in the ICU with SAKI by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations. TRIAL REGISTRATION: NCT03175328.

Transcriptomic profiling of cotton Gossypium hirsutum challenged with low-temperature gradients stress.

Gossypium hirsutum, a cotton species widely cultivated around the world, is a typical cold-sensitive crop. Low-temperature (LT) stress is one of the main environmental stressors that can affect growth and the quality of cotton fibers. LT is also a major challenge for cotton survival, growth maturity and geographical distribution. However, few genome-wide transcriptional response and profiling datasets are available to explore the LT-tolerant mechanism of cotton. This study treated G. hirsutum with four LT gradients (control at 25 °C and cold temperatures at 4 °C, 10 °C and 15 °C) for 24 hour to generate 12 RNA-Seq datasets (three biological replicates per treatment) with approximately 280 million clean reads per dataset. The quality of the datasets obtained in the current study was validated through a series of quality checks including verification of RNA sample quality and RNA-Seq read quality. Data analyses included novel gene discovery, global gene expression profiling and quantitative real-time PCR. This is the first study to report genome-wide transcriptomic datasets for cotton in response to LT exposure.

Extracorporeal Membrane Oxygenation Outcomes in Acute Respiratory Distress Treatment: Case Study in a Chinese Referral Center.

BACKGROUND No definitive conclusions have been drawn from the available data about the utilization of extracorporeal membrane oxygenation (ECMO) to treat severe acute respiratory distress syndrome (ARDS). The aim of this study was to review our center's experience with ECMO and determine predictors of outcome from our Chinese center. MATERIAL AND METHODS We retrospectively analyzed a total of 23 consecutive candidates who fulfilled the study entry criteria between January 2009 and December 2015. Detailed clinical data, ECMO flow, and respiratory parameters before and after the introduction of ECMO were compared among in-hospital survivors and nonsurvivors; factors associated with mortality were investigated. RESULTS Hemodynamics and oxygenation parameters were significantly improved after ECMO initiation. Thirteen patients survived to hospital discharge. Univariate correlation analysis demonstrated that APACHE II score (r=-0.463, p=0.03), acute kidney injury (r=-0.574, p=0.005), membrane oxygenator replacement (r=-0.516, p=0.014) and total length of hospital stay (r=0.526, p=0.012) were significantly correlated with survival to hospital discharge, and that the evolution of the levels of urea nitrogen, platelet, and fibrinogen may help to determine patient prognosis. Sixteen patients referred for ECMO from an outside hospital were successfully transported to our institution by ambulance, including seven transported under ECMO support. The survival rate of the ECMO-transport group was comparable to the conventional transport or the non-transport group (both p=1.000). CONCLUSIONS ECMO is an effective alternative option for severe ARDS. APACHE II score on admission, onset of acute kidney injury, and membrane oxygenator replacement, and the evolution of levels of urea nitrogen, platelet, and fibrinogen during hospitalization may help to determine the in-hospital patient prognosis. By establishing a well-trained mobile ECMO team, a long-distance, inter-hospital transport can be administered safely.

Construction of boronate ester based single-layered covalent organic frameworks.

Boronate ester based single-layered covalent organic frameworks (sCOFs) with large domain areas and uniform pore sizes have been fabricated on graphite under an ambient atmosphere. The phase separation to generate the boronate ester based sCOFs, boroxine based sCOFs and other nanostructures could be tuned using the molecular ratio of the two precursors, demonstrating a self-sorting process for on-surface dynamic covalent chemistry.

Performance of Multiple Risk Assessment Tools to Predict Mortality for Adult Respiratory Distress Syndrome with Extracorporeal Membrane Oxygenation Therapy: An External Validation Study Based on Chinese Single-center Data.

BACKGROUND: There has been no external validation of survival prediction models for severe adult respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO) therapy in China. The aim of study was to compare the performance of multiple models recently developed for patients with ARDS undergoing ECMO based on Chinese single-center data. METHODS: A retrospective case study was performed, including twenty-three severe ARDS patients who received ECMO from January 2009 to July 2015. The PRESERVE (Predicting death for severe ARDS on VV-ECMO), ECMOnet, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score, a center-specific model developed for inter-hospital transfers receiving ECMO, and the classical risk-prediction scores of Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) were calculated. In-hospital and six-month mortality were regarded as the endpoints and model performance was evaluated by comparing the area under the receiver operating characteristic curve (AUC). RESULTS: The RESP and APACHE II scores showed excellent discriminate performance in predicting survival with AUC of 0.835 (95% confidence interval [CI], 0.659-1.010, P = 0.007) and 0.762 (95% CI, 0.558-0.965, P = 0.035), respectively. The optimal cutoff values were risk class 3.5 for RESP and 35.5 for APACHE II score, and both showed 70.0% sensitivity and 84.6% specificity. The excellent performance of these models was also evident for the pneumonia etiological subgroup, for which the SOFA score was also shown to be predictive, with an AUC of 0.790 (95% CI, 0.571-1.009, P = 0.038). However, the ECMOnet and the score developed for externally retrieved ECMO patients failed to demonstrate significant discriminate power for the overall cohort. The PRESERVE model was unable to be evaluated fully since only one patient died six months postdischarge. CONCLUSIONS: The RESP, APCHAE II, and SOFA scorings systems show good predictive value for intra-hospital survival of ARDS patients treated with ECMO in our single-center evaluation. Future validation should include a larger study with either more patients' data at single-center or by integration of domestic multi-center data. Development of a scoring system with national characteristics might be warranted.

Comparison of the pulmonary dead-space fraction derived from ventilator volumetric capnography and a validated equation in the survival prediction of patients with acute respiratory distress syndrome.

PURPOSE: This prospective observational study aims to evaluate the accuracy of dead-space fraction derived from the ventilator volumetric capnography (volumetric CO2) or a prediction equation to predict the survival of mechanically ventilated patients with acute respiratory distress syndrome (ARDS). METHODS: Consecutive VD/VT measurements were obtained based upon a prediction equation validated by Frankenfield et al for dead-space ventilation fraction: VD/VT = 0.320 + 0.0106 (PaCO2-ETCO2)⁺ 0.003 (RR)⁺0.0015 (age) in adult patients who had infection-related severe pneumonia and were confirmed as having ARDS. Here PaCO2 is the arterial partial pressure of carbon dioxide in mmHg; ETCO2, the end- tidal carbon dioxide measurement in mmHg; RR, respiratory rate per minute; and age in years. Once the patient had intubation, positive end expiratory pressure was adjusted and after Phigh reached a steady state, VD/VT was measured and recorded as the data for the first day. VD/VT measurement was repeated on days 2, 3, 4, 5 and 6. Meanwhile we collected dead-space fraction directly from the ventilator volu- metric CO2 and recorded it as Vd/Vt. We analyzed the changes in VD/VT and Vd/Vt over the 6-day period to determine their accuracy in predicting the survival of ARDS patients. RESULTS: Overall, 46 patients with ARDS met the inclusion criteria and 24 of them died. During the first 6 days of intubation, VD/VT was significantly higher in nonsurvivors on day 4 (0.70 ± 0.01 vs 0.57 ± 0.01), day 5 (0.73 ± 0.01 vs. 0.54 ± 0.01), and day 6 (0.73 ± 0.02 vs. 0.54 ± 0.01) (all p =0.000). Vd/Vt showed no significant difference on days 1e4 but it was much higher in nonsurvivors on day 5 (0.45 ± 0.04 vs. 0.41 ± 0.06) and day 6 (0.47 ± 0.05 vs. 0.40 ± 0.03) (both p=0.008). VD/VT on the fourth day was more accurate to predict survival than Vd/Vt. The area under the receiver-operating characteristic curve for VD/VT and Vd/Vt in evaluating ARDS patients survival was day 4 (0.974 ± 0.093 vs. 0.701 ± 0.023, p = 0.0024) with the 95% confidence interval being 0.857-0.999 vs. 0.525-0.841. CONCLUSION: Compared with Vd/Vt derived from ventilator volumetric CO2, VD/VT on day 4 calculated by Frankenfield et al's equation can more accurately predict the survival of ARDS patients.

Clinical study of midazolam sequential with dexmedetomidine for agitated patients undergoing weaning to implement light sedation in intensive care unit.

PURPOSE: To evaluate midazolam sequential with dexmedetomidine for agitated patients undergoing weaning to implement light sedation in ICU. METHODS: This randomized, prospective study was conducted in Tianjin Third Central Hospital, China. Using a sealed-envelope method, the patients were randomly divided into 2 groups (40 patients per group). Each patient of group A received an initial loading dose of midazolam at 0.3-3mg/kg·h 24 h before extubation, followed by an infusion of dexmedetomidine at a rate of 0.2-1 µg/kg·h until extubation. Each patient of group B received midazolam at a dose of 0.3-3 mg/kg·h until extubation. The dose of sedation was regulated according to RASS sedative scores maintaining in the range of -2-1. All patients were continuously monitored for 60 min after extubation. During the course, heart rate (HR), mean artery pressure (MAP), extubation time, adverse reactions, ICU stay, and hospital stay were observed and recorded continuously at the following time points: 24 h before extubation (T1), 12 h before extubation (T2), extubation (T3), 30 min after extubation (T4), 60 min after extubation (T5). RESULTS: Both groups reached the goal of sedation needed for ICU patients. Dexmedetomidine was associated with a significant increase in extubation quality compared with midazolam, reflected in the prevalence of delirium after extubation (20% (8/40) vs 45% (18/40)), respectively (p= 0.017). There were no clinically significant decreases in HR and MAP after infusing dexmedetomidine or midazolam. In the group A, HR was not significantly increased after extubation; however, in the group B, HR was significantly increased compared with the preextubation values (p < 0.05). HR was significantly higher in the group B compared with the group A at 30 and 60 min after extubation (both, p <0.05). Compared with preextubation values, MAP was significantly increased at extubation in the group B (p < 0.05) and MAP was significantly higher at T3, T4, T5 in the group B than group A (p < 0.05). There was a significant difference in extubation time ((3.0 ± 1.5) d vs (4.3 ± 2.2) d, p < 0.05), ICU stay ((5.4 ± 2.1) d vs (8.0 ± 1.4) d, p < 0.05), hospital stay ((10.1 ± 3.0) d vs (15.3 ± 2.6) d, p <0.05) between group A and B. CONCLUSION: Midazolam sequential with dexmedetomidine can reach the goal of sedation for ICU agitated patients, meanwhile it can maintain the respiratory and circulation parameters and reduce adverse reactions.

[A multicenter study of respiratory multiple index in predicting weaning from mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To study the result of respiratory multiple index(compliance, respiratory rate, oxygenation, pressure, CROP) in predicting weaning from mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A prospective study was conducted. Two hundred and fifteen patients weaning from mechanical ventilation with AECOPD in intensive care unit (ICU) of five tertiary hospitals from September 2010 to October 2012 were enrolled. All of the AECOPD patients were troubled with respiratory failure and received non-invasive mechanical ventilation for more than 24 hours. They were conscious and cooperative at the time of extubation, and passed the spontaneous breathing trial (SBT) for 30 minutes. Before weaning, the maximal inspiratory pressure (PImax), the peak airway pressure (Ppeak), the total positive end expiratory pressure (PEEPtot), tidal volume (VT) and respiratory frequency (f) were recorded; the arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2) were detected; the effective compliance of the respiratory system (Crs) and alveolar oxygen pressure(PAO2) were calculated. The above indexes were substituted into the formula: CROP= Crs × 1/f × PaO2/PAO2× PImax to get the value of CROP. Successful weaning from mechanical ventilation was defined if there was no indication for intubation within 72 hours. The receiver operating characteristic curve (ROC curve) was drawn to analyze the predict value of CROP on result of weaning from mechanical ventilation in patients with AECOPD. RESULTS: In 215 patients, 182 patients successfully weaned from mechanical ventilation, and 33 failed. There were no significant differences in gender, age and the acute physiology and chronic health evaluation II (APACHEII) score between the successfully weaned patients and the failed. Before weaning from mechanical ventilation, PaCO2 in failed group was significantly higher than that in successful group (60.69 ± 10.47 mm Hg vs. 51.24 ± 8.81 mm Hg, P<0.05), the CROP was significantly lowered (10.286 ± 1.392 ml × breath⁻¹ ×min⁻¹ vs. 58.746 ± 7.283 ml×breath⁻¹×min⁻¹, P<0.01), and the duration of mechanical ventilation was prolonged (10.28 ± 3.94 days vs. 6.21 ± 2.87 days, P<0.05). The best critical value of CROP which could predict the result of weaning from mechanical ventilation was 13.521 ml×breath⁻¹×min⁻¹. CROP≥ 13.521 ml×breath⁻¹×min⁻¹ had a specificity of 91.9% and sensitivity of 87.9% in predicting extubation succeed. The positive predicted value was 0.97, and the negative predicted value was 0.58; Odds ratio (OR)<1, which confirmed that CROP was a strong and independent predictor of extubation. CONCLUSIONS: For the AECOPD patients received mechanical ventilation, most extubation parameter was limited. Complex parameter of CROP has higher specificity and sensitivity, and has important value in predicting extubation outcome. When CROP ≥ 13.521 ml×breath⁻¹×min⁻¹, the successful rate is high, otherwise the rate is low.

[A preliminary study of using the expiratory limb of the pressure-volume curve to estimate the dead space in patients suffering from acute respiratory distress syndrome].

OBJECTIVE: To trace pressure-volume curves (P-V curves) with quasi-static technique in acute respiratory distress syndrome (ARDS) patients, and using it to explain the relationship between the end point of the expiratory limb and the change in the dead space of expiration. METHODS: A prospective study was conducted. Fourteen ARDS patients receiving mechanical ventilation were included in the study. When P-V curves were traced with quasi-static technique, the spirometer was connected to the flow sensor. The start point of the expiratory limb was defined as tidal volume 1 (VT1) and the end point as VT2, and the difference between them (ΔVT=VT1-VT2) was calculated. The VT of spirometer (named VT3) and the predetermined VT (VT4) were recorded. Correlations of ΔVT and VT3, as well as VT4 and VT1, were analyzed with correlation analysis. RESULTS: ΔVTwas (417.40±119.68) ml, and VT3 was (399.29±121.36) ml, ΔVT and VT3 showed a good correlation (r=0.99, P=0.000), demonstrating that the ΔVT of the expiratory limb was correlated with the volume trapped in lung. VT4 was (908.21±106.52) ml, and VT1 was(892.26±106.32) ml, and they showed a good correlation (r=0.99, P=0.000). CONCLUSION: Because of part of the gas trapped at the end of expiration in ARDS patients, the dead space is increased, showing that the expiratory limb of the P-V curve cannot return to the base points, and the ΔVT of the expiratory limb is inversely proportional to the gas volume trapped in lung.

[The study of continuous blood purification in severe asthma].

OBJECTIVE: To explore the mechanism that continuous blood purification (CBP) improve the lung mechanical ventilation parameters, cytokine levels and blood gas analysis results in severe asthma patients, and compare the differences in those parameters between bicarbonate and lactate displacement liquid. METHODS: According to the random number table, 26 severe asthma patients were allocated into control group (n=10), bicarbonate group (n=8) and lactate group (n=8). Twenty-four hours treatment with mechanical ventilation (control group), mechanical ventilation + CBP (bicarbonate group) or mechanical ventilation + CBP (lactate group) were conducted respectively. Lung mechanical ventilation parameters, serum cytokine level and blood gas analysis results, arterial blood lactate, and electrolytes level were compared among groups. RESULTS: After 24-hour CBP, the lung mechanical ventilation parameters were improved, cytokine levels were decreased, and pH value and partial pressure of oxygen were improved in bicarbonate group and lactate group. The two kinds of displacement liquid had no influence in arterial partial pressure of oxygen (PaO(2)), arterial blood lactate, and serum electrolytes level. The pH value in lactate group was higher than that in bicarbonate group (7.39±0.05 vs. 7.30±0.01, P<0.01). The arterial partial pressure of carbon dioxide (PaCO(2)) was lower in lactate group than that in bicarbonate group (57.14±5.04 mm Hg vs. 89.00±3.66 mm Hg, P<0.01). CONCLUSIONS: Combine CBP might improve the lung mechanical ventilation parameter, cytokine level and blood gas analysis more quickly in severe asthma treatment. The lactate displacement liquid improves the retention of carbon dioxide more.

[Clinical research of using optimal compliance to determine positive end-expiratory pressure].

OBJECTIVE: To observe the availability and security of optimal compliance strategy to titrate the optimal positive end-expiratory pressure (PEEP), compared with quasi-static pressure-volume curve (P-V curve) traced by low-flow method. METHODS: Fourteen patients received mechanical ventilation with acute respiratory distress syndrome (ARDS) admitted in intensive care unit (ICU) of Tianjin Third Central Hospital from November 2009 to December 2010 were divided into two groups(n = 7). The quasi-static P-V curve method and the optimal compliance titration were used to set the optimal PEEP respectively, repeated 3 times in a row. The optimal PEEP and the consistency of repeated experiments were compared between groups. The hemodynamic parameters, oxygenation index (OI), lung compliance (C), cytokines and pulmonary surfactant-associated protein D (SP-D) concentration in plasma before and 2, 4, and 6 hours after the experiment were observed in each group. RESULTS: (1) There were no significant differences in gender, age and severity of disease between two groups. (2)The optimal PEEP [cm H(2)O, 1 cm H(2)O=0.098 kPa] had no significant difference between quasi-static P-V curve method group and the optimal compliance titration group (11.53 ± 2.07 vs. 10.57 ± 0.87, P>0.05). The consistency of repeated experiments in quasi-static P-V curve method group was poor, the slope of the quasi-static P-V curve in repeated experiments showed downward tendency. The optimal PEEP was increasing in each measure. There was significant difference between the first and the third time (10.00 ± 1.58 vs. 12.80 ± 1.92, P < 0.05). And the optimal compliance titration method had good reproducibility as the optimal PEEP without significant difference in each measure. (3) After the quasi-static P-V curve traced, the heart rate (HR, bpm), temperature (centigrade), interleukin-6 (IL-6, ng/L), tumor necrosis factor-α (TNF-α, ng/L), SP-D (µg/L) showed a gradually increasing tendency, the mean artery pressure (MAP, mm Hg, 1 mm Hg = 0.133 kPa), continuous cardiac index [CCI, L×min(-1)×m(-2)], OI (mm Hg), and C [ml/cm H(2)O] showed a gradually decreased tendency, all of these parameters reached the peak or trough at 6 hours after the experiment, and there was significance compared with those before experiment (HR: 117.34 ± 8.53 vs. 93.71 ± 5.38, temperature: 38.05 ± 0.73 vs. 36.99 ± 1.02, IL-6: 144.84 ± 23.89 vs. 94.73 ± 5.91, TNF-α: 151.46 ± 46.00 vs. 89.86 ± 13.13, SP-D: 33.65 ± 8.66 vs. 16.63 ± 5.61, MAP: 85.47 ± 9.24 vs. 102.43 ± 8.38, CCI: 3.00 ± 0.48 vs. 3.81 ± 0.81, OI: 62.00 ± 21.45 vs. 103.40 ± 37.27, C: 32.10 ± 2.92 vs. 49.57 ± 7.18, all P < 0.05). The results suggested that the drawing of quasi-static P-V curve would aggravate the lung injury. And in optimal compliance titration method group, there were no significant differences in HR, MAP, temperature, CCI, OI, C, cytokines and SP-D before and after titration. CONCLUSION: Optimal compliance titration method has good reproducibility, safety and usability.

[The lung protection strategy under the support of extracorporeal membrane oxygenation in patients suffering from influenza A H1N1].

OBJECTIVE: To study the effect of extracorporeal membrane oxygenation (ECMO) in patients suffering from severe pneumonia complicating influenza A H1N1 by putting lungs in rest to protect the latter. METHODS: Five patients with severe pneumonia following influenza A H1N1 were treated with ECMO and different modes of mechanical ventilation at the same time. Two patients died, both of them received synchronized intermittent mandatory ventilation (SIMV) and bi-level positive airway pressure (BiPAP) modes, with airway pressure release ventilation (APRV) to control lung expansion with expansion pressure 40 cm H(2)O (1 cm H(2)O=0.098 kPa). In 3 survivors, the strategy of lung rest was performed by giving an optimized positive end expiratory pressure (PEEP) with an optimal compliance by gradually elevation of PEEP, and high-level pressure (Phigh) at 20 cm H(2)O by application of BiPAP mode. RESULTS: One patient died due to lung damage and repeated spontaneous pneumothorax and sepsis; 1 patient died due to multiple organ dysfunction syndrome. Three patients recovered after following the strategy of lung rest. CONCLUSION: When ECMO is used for severe pneumonia complicating influenza A H1N1, prognosis can be obviously improved, with decrease in the occurrence of lung damage through the protection strategy of lung rest.

[Study on the effect of control mode of pressure and volume on cardiac index and intrathoracic blood volume index in critically ill patients].

OBJECTIVE: To compare the effect of control mode of pressure and volume of mechanical ventilation on cardiac index (CI), intrathoracic blood volume index (ITBVI) in patients. METHODS: Twenty-four patients in whom mechanical ventilation and pulse indicator continuous cardiac output (PiCCO) monitoring were necessary were involved, and they were divided into normal heart function group (9 cases) and heart dysfunction group (15 cases) on the base of CI. Mechanical ventilation was used with the mode of bi-level positive airway passage (BIPAP), and the inspiratory pressure was maintained at the tidal volume (V(T)) of 6, 10, 15 ml/kg. After the mechanical ventilation mode was changed to synchronized intermittent mandatory ventilation (SIMV) and maintained for 20 minutes, breathing mechanics and central venous pressure (CVP), CI, ITBVI were measured. RESULTS: In the normal heart function group, there were decrease in mean arterial pressure (MAP), CI and ITBVI, increase in heart rate (HR), mean airway pressure (Pmean) and intrinsic positive end expiratory pressure (PEEPi) in both modes of mechanical ventilation without significant difference (P values were 0.067, 0.124, 0.348, 0.328, 0.110, 0.187, respectively). Systemic vascular resistance index (SVRI) was higher in the BIPAP group compared with SIMV group (P=0.030). In the heart dysfunction group, the CI and ITBVI were decreased in the SIMV mode, and CI was decreased significantly in the 10 ml/kg group (P<0.05). Pmean in BIPAP group was increased than that in SIMV group in all V(T) levels (P values were 0.003, 0.000, 0.004, respectively). There was no significant difference in SVRI, HR, MAP and PEEPi in all groups. CONCLUSION: In the two mechanical ventilation modes, with an increase in V(T), CI and ITBVI may decrease. The Pmean is lower when BIPAP mode in used compared with SIMV, when V(T) is same. So mechanical ventilation and V(T) can influence the readings of CI and ITBVI when PiCCO monitoring is employed.

[Characteristics of six elements contents in human hairs in the vicinity of metal smelting factories].

To assess the impact of secondary smelting activities to the local resident's well beings, the contents of six elements-Cu, Zn, Pb, Cd, As, Se-in human scalp hairs of residents in suburb Fuyang, Zhejiang Province, were determined by atomic absorption spectrometer (AAS) and by atomic fluorescence spectrometer (AFS-930), respectively. The results showed that hair elemental contents were markedly higher than those in unpolluted area. The highest hair contents of Cu, Zn, Pb and Cd reached 312, 513, 700 and 7.41 microg x g(-1), respectively, As and Se 10.08 and 0.85 microg x g(-1), respectively. Additionally, a significant relationship between Cu, Zn, Pb, Cd and As in human hair was observed, which indicated at a certain degree that the elemental pollution was caused by similar source-small blast furnace smelting. Moreover, it showed that the Cu, Zn, Pb, Cd, and As contents in hair of human who were above 40 years old was twice more than those whose age below 40. There was no apparent difference in average content of Cu, Zn, Cd, Se between male and female, except that Pb and As of male hair was higher than female, however, by statistic analysis showing no significant age and gender dependence.

Benzobijuglone, a novel cytotoxic compound from Juglans mandshurica, induced apoptosis in HeLa cervical cancer cells.

A new quinone compound, p-hydroxymethoxybenzobijuglone (HMBBJ), isolated from Juglans mandshurica by bioassay-guided fractionation, showed cytotoxic activity against HeLa cell line. Its chemical structure was determined by NMR and HREIMS spectra. In this paper, its ability to induce apoptosis in HeLa cells was studied for the first time. After treated with HMBBJ, the growth of HeLa cells was inhibited and cells displayed typical morphological apoptotic characteristics. Data from flow cytometry analysis showed that the HeLa cell cycle was arrested in the G2/M phase by HMBBJ, and the apoptotic rate of HeLa cells increased in a dose-dependent manner. Meanwhile, HMBBJ increased the expression of caspase-8, -3 and Bax, decreased the expression of Bcl-2, and lowered the DeltaPsi(m). These findings reveal that HMBBJ could efficiently induce HeLa cells apoptosis through mitochondria dependent pathway and activation of the caspase cascade, and it may be a potential chemotherapeutic candidate for the treatment of cancer.

Catalpol ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose.

The neuroprotective effects of catalpol, an iridoid glycoside isolated from the fresh Rehmannia roots, on the senescent mice induced by D-galactose were assessed. The mice subcutaneously injected with catalpol (5 or 10 mg/kg, 2 weeks, from fifth week) showed significantly improved learning and memory ability in Morris water maze test compared with d-galactose treated mice (150 mg/kg, 6 weeks). We further investigated the mechanism involved in the neuroprotective effects of catalpol on the mice brain tissue. The results showed that catalpol increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), decreased the malondialdehyde (MDA) level, elevated the activities of Na+ -K+ ATPase and Ca2+ -Mg2+ ATPase on the cerebral cortex and hippocampus of d-galactose treated mouse. All the data suggested that catalpol had the potential to be a useful cognitive impairment treatment, and its beneficial effects may be partly mediated via enhancing endogenous antioxidant enzymatic activities and inhibiting free radical generation.

[Study on the preparation of rapid-dissoluted EGb droppills].

OBJECTIVE: To study the formulation and technique of preparation of rapid-dissoluted EGb (Extract of Ginkgo biloba) droppills. METHOD: Taking the dissolution percentage of total flavonoids in EGb and weight variation as index, the formulation and technique of EGb droppills were optimized by the orthogonal experiment. RESULT: T50 was 3.62 min and mean weight variation was 2.80%. CONCLUSION: Rapid-dissoluted EGb droppills can increase the dissoluting rate distinctly and reach the purpose of preparation.