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This article summarizes the new progress in the diagnosis and treatment strategies on drug-resistant cytomegalovirus(CMV)infections in organ transplant recipients, including the prevention and treatment medications for CMV infection, the diagnosis and treatment strategies, and the immunological treatment regimen for drug-resistant CMV infection.The article is aimed to provide references for the prevention and treatment of drug-resistant CMV infection in organ transplant recipients.
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Objective: This study was designed to investigate the protective effects of didymin (Did) on doxorubicin (DOX)-induced cardiotoxicity. Methods: After pretreatment with Did (2, 4, 8 mg/kg intraperitoneal i.p.) for 7 d, the male C57 mice were injected with single dose of DOX (20 mg/kg i.p.). The cardioprotective effect of Did was observed on the 7th day after DOX treatment. Results: DOX delayed body growth and caused cardiac tissue injury, oxidative stress, and mitochondrial dysfunction. Similar experiments in H9C2 cardiomyocytes showed that DOX reduced cell viability, increased generation of reactive oxygen species (ROS) and fragmentation of DNA, decreased mitochondrial membrane potential, and induced cardiomyocyte apoptosis. However, all of these adverse effects were suppressed by Did pretreatment. Did increased protein expression of glutamate-L-cysteine ligase catalytic subunit (GCL), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Besides, Did also induced activation of PI3K/AKT. Conclusion: These findings indicated Did prevented DOX-induced cardiac injury and apoptosis via activating PI3K/AKT/Nrf2 signaling pathway.
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Objective:To explore whether the adoption of high-flow nasal cannula (HFNC) as an initial oxygen therapy in emergency department (ED) could reduce the intubation rate and improve the clinical outcomes of patients with dyspnea and hypoxemia compared with conventional oxygen therapy (COT).Methods:A perspective single-center randomized controlled trial was conducted in the First Affiliated Hospital of Zhengzhou University from October 1, 2019 to September 30, 2020. A total of 210 eligible patients with acute dyspnea and hypoxemia in ED were recruited and randomized (in 1:1) to receive HFNC or COT for 1 h immediately after the grouping. The primary outcome was the rate of intubation within 24 h. The secondary outcomes included total intubation rate, escalation of breathing support method, patients’ disposition, length of ICU stay and hospital mortality. Continuous outcomes were analyzed by independent samples t test or Mann-Whitney U test according to the data distribution. Discontinuous outcomes were compared with the Chi-square test. Kaplan-Meier curve analysis was performed for 60-day survival. Results:Finally, 105 patients were recruited in each group. HFNC reduced the intubation rate within the first 24 h (4.8% vs. 14.3%, P = 0.019) and the rate of patients escalated to upgrade oxygen therapy (34.3% vs. 53.3%, P = 0.005), but did not affect the total intubation rate during the whole attendance ( P = 0.509). In ED, HFNC helped more patients to achieve the targeted saturation of pulse oxygen (90.5% vs. 78.1%, P = 0.02), and reduced respiratory rate (RR) to < 25 breaths per min (68.6% vs. 49.0%, P = 0.004), but did not affect the length of hospital stay, hospital mortality and 60-day survival rate ( P > 0.05). Conclusions:Initial application of HFNC in ED could reduce the intubation rate within 24 h, decrease the rate of escalation of oxygen therapy, improve oxygenation and relieve dyspnea.
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Objective:To investigate the characteristics of newly diagnosed patients with chronic obstructive pulmonary disease (COPD) in Shenzhen primary care.Methods:Random sampling was conducted in 10 jurisdictions of Shenzhen, permanent residents who were over 40 years old and lived for more than 6 months were included for lung function test, COPD Population Screener (COPD-PS) questionnaire and information survey, the prevalence of COPD was estimated, and statistical comparison was made between the two groups of subjects with newly diagnosed and previously diagnosed COPD.Results:Among 3 916 subjects, 3 591 had completed the whole screening process. The results showed that 280 COPD patients were diagnosed and the estimated standardized prevalence of COPD was 5.92% (95% CI: 4.05-8.34). Among them, 251 (89.64%) were newly diagnosed COPD patients and 29 (10.36%) were previously diagnosed COPD patients. Compared with previously diagnosed COPD, the proportion of female in the newly diagnosed COPD was higher (50.20% vs 10.34%, P<0.001), educational level in the newly diagnosed COPD was lower (the proportion of primary school and below was higher, 42.23% vs 20.69%, P=0.023), the proportion of those with frequent wheezing symptoms in the newly diagnosed COPD was lower (4.78% vs 51.72%, P<0.001), the proportion of those with mild degree of airway obstruction (GOLD 1) in the newly diagnosed COPD was higher (81.67% vs 20.69%, P<0.001). The detection rates of COPD-PS in newly diagnosed COPD and previously diagnosed COPD were 43.03% and 41.38% respectively. The area under the receiver operating characteristic curve of COPD-PS was 0.705. Conclusion:The phenomenon of insufficient diagnosis of COPD in Shenzhen primary care is common and we should vigorously popularize pulmonary function examination.
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Realtime xCELLigence analysis (RTCA) is a new cell detection technology to continuously monitor, record and analyze a variety of information generated by cell activity. In drug research, it plays an important role in assessing myocardial toxicity and cell biological activity. Here, we first introduce the underlying mechanisms and characteristics of RTCA. Then we review the applications of RTCA in the research of myocardial toxicity and cell biological activity, to provides the fundamental baseline for understanding and exploiting RTCA. With the real-time, unlabeled, non-invasive, high throughput, and high accuracy features, RTCA not only promotes drug research and development, but also has a broad and good application prospect in other fields.
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Objective:To investigate the effect and tolerance of non-invasive ventilation (NIV) with helmet in patients with respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the effect on improving blood gas, alleviating dyspnea and the occurrence of complications.Methods:Patients with AECOPD and respiratory failure admitted to emergency intensive care unit (EICU) and respiratory intensive care unit (RICU) of the First Affiliated Hospital of Zhengzhou University from January 1st, 2018 to May 31st, 2019 were enrolled. After obtaining the informed consent of the patients or their authorized family members, the patients were divided into two groups: the helmet group and the facial mask group by random number table. NIV was carried out by using helmet or facial mask, respectively. During the course of NIV (immediately, 1 hour, 4 hours and at the end of NIV), the tolerance score, blood gas analysis, heart rate (HR), respiratory rate (RR) of patients were monitored, and the incidence of tracheal intubation, in-hospital mortality and complications were observed. Kaplan-Meier survival curve was plotted to analyze the 30-day cumulative survival of the two groups.Results:A total of 82 patients with AECOPD and respiratory failure were included during the study period. After excluding patients with the oxygenation index (PaO 2/FiO 2) > 200 mmHg (1 mmHg = 0.133 kPa), with tracheal intubation or invasive ventilation, suffering from acute myocardial infarction, severe trauma within 2 weeks, excessive secretion, sputum discharge disorder or refusal to participate in the study, 26 patients were finally enrolled in the analysis, randomly assigned to the helmet group and the facial mask group, with 13 patients in each group. The PaO 2/FiO 2 after NIV of patients in both groups was increased significantly as compared with that immediately after NIV, without significant difference between the two groups, but the increase in PaO 2/FiO 2 at the end of NIV compared with immediately after NIV in the helmet group was significantly higher than that in the facial mask group (mmHg: 75.1±73.2 vs. 7.7±86.0, P < 0.05). RR at each time point after NIV in the two groups was lower than that immediately after NIV, especially in the helmet group. There were significant differences between the helmet group and facial mask group at 1 hour, 4 hours, and the end of NIV (times/min: 17.5±4.1 vs. 23.1±6.3 at 1 hour, 16.2±2.5 vs. 20.0±5.5 at 4 hours, 15.5±2.5 vs. 21.2±5.9 at the end of NIV, all P < 0.05). The NIV tolerance score of the helmet group at 4 hours and the end was significantly higher than that of the facial mask group (4 hours: 3.9±0.3 vs. 3.3±0.9, at the end of NIV: 3.8±0.6 vs. 2.9±0.9, both P < 0.05). There was no significant difference in the improvement of pH value, arterial partial pressure of carbon dioxide (PaCO 2), or HR between helmet group and facial mask group. The total number of complications (cases: 3 vs. 8) and the nasal skin lesions (cases: 0 vs. 4) in the helmet group were significantly less than those in the facial mask group (both P < 0.05). Only 2 patients in the helmet group received endotracheal intubation, and 1 of them died; 5 patients in the facial mask group received endotracheal intubation, and 3 of them died; there was no significant difference between the two groups (both P > 0.05). The Kaplan-Meier survival curve analysis showed that the cumulative survival rate of 30 days in the helmet group was lower than that in the facial mask group, but the difference was not statistically significant (Log-Rank test: χ 2 = 1.278, P = 0.258). Conclusion:NIV with helmet has better comfort for patients with AECOPD combined with respiratory failure, and better effect on improving oxygenation and relieving dyspnea, and its effect on carbon dioxide emissions is not inferior to that of traditional mask NIV.
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Purpose@#Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. @*Methods@#TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. @*Results@#TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. @*Conclusions@#These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.
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Purpose@#Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. @*Methods@#TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. @*Results@#TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. @*Conclusions@#These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.
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Objective:To explore the diagnosis and treatment strategies of primary ciliary dyskinesia (PCD).Methods:A 37-year-old male recipient who had repeated cough and sputum from childhood, with shortness of breath after activity and progressive development, the number of hospitalizations per year was ≥6 times, the MRC score was 2~3 diagnosed with primary ciliary dyskinesia through medical examination and multidisciplinary consultation, and received allogeneic double lung transplantation after medical treatment failure. Search related domestic and foreign literatures to explore and analyze the etiology, pathogenesis, clinical manifestations and imaging features, diagnosis and treatment of PCD.Results:PCD is an autosomal hereditary disease. Due to abnormal skeletal structure and/or functional development, clinical manifestations are mostly chronic sinusitis, bronchiectasis, otitis media and infertility. Chest imaging showed situs inversus totalis, right heart and diffuse cystic bronchiectasis infection with bronchial wall thickening, diagnosis depends on clinical manifestations, saccharin test, nasal nitric oxide test, high-speed video microscopy analysis, transmission electron microscopy, genetic testing and immunofluorescence.Conclusions:Lung transplantation is the only effective treatment for end-stage PCD. It not only saves patients' lives, but also significantly improves their quality of life.
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Objective To explore the effect of noninvasive ventilation (NIV) with helmet or facial mask on clinical efficacy, tolerability, and prognosis in patients with acute respiratory failure. Methods Fifty patients with acute respiratory failure according to the inclusion criteria were recruited from January 2018 to July 2018 in Emergency Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University. Included patients were randomly allocated into the helmet group or facial mask group. Based on conventional drug therapy, pressure support mode was performed with the interface of the helmet or facial mask. Oxygenation index, arterial carbon dioxide partial pressure, and respiratory rates were measured before and after the treatment, and the data were compared and analyzed by the repeated measures ANOVA. Tolerance score, complication rate, tracheal intubation rate, and mortality rate were recorded at each observation time point of the two groups. Results The oxygenation index before NIV, at 4 h and at the end of NIV treatment of the helmet group were significantly increased from (160.29±50.32) mmHg to (249.29±83.47) mmHg and (259.24±87.09) mmHg; the oxygenation index of the facial mask group were increased from (168.63±38.63) mmHg to (225.00±74.96) mmHg and (217.69±77.80) mmHg, and there was no significant difference within the two groups (P <0.05). The respiratory rates before NIV, at 4 h and at the end of NIV treatment of the helmet group were obviously decreased from (27.60±7.64) breaths/min to (17.92±4.55) breaths/min and (16.88±3.90) breaths/min; the respiratory rates of the facial mask group were decreased from (24.68±6.14) breaths/min to (20.36±4.25) breaths/min and (19.68±3.34) breaths/min, and the differences within the two groups were statistically significant (P <0.05). However, there were no significant differences on oxygenation index and respiratory rates between the helmet group and facial mask group (P >0.05). Patients in the helmet was better tolerated than those in the facial mask group [ratio of good tolerance 96％ (24/25) vs 56％ (14/25) (P = 0.001) and fully tolerance 80％ (20/25) vs 36％ (9/25) (P =0.002)] and had less complications (1/25 vs 10/25, P = 0.002). 84％ patients in the helmet group and 76％ patients in the facial mask group were successfully weaned and discharged after NIV treatment (P =0.480). Conclusions Similar clinical efficacy in improving blood gas exchange and relieving dyspnea were observed in the helmet group and the facial mask group in patients with acute respiratory failure. However, the helmet is better tolerant, and had lower complication rate, which is especially suitable for patients with chest trauma combined with facial injuries.
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Objective To explore the treatment strategies of pleuroparenchymal fibroelastosis (PPFE). Methods A 22-year-old male patient was complicated with PPFE after receiving chemotherapy in combination with stem cell transplantation for lymphoma. He underwent thoracoscopic left lung tongue wedge resection, bilateral pleurodesis followed by allogeneic left lung transplantation. Literature review was performed to analyze the etiology, pathogenesis, imaging features, pathological features and treatment of PPFE. Results The PPFE patient required the non-invasive ventilator for 24 h before lung transplantation. After lung transplantation, the shortness of breath and respiratory failure were cured and the quality of life was significantly improved. No eligible studies was found in the domestic database, and 26 literatures published in English were found in the international databases. Among them, 9 literatures (case reports) were finally included after screening. PPFE could be divided into the primary and secondary categories according to the etiology. The clinical manifestations of PPFE mainly included dry cough, dyspnea on exertion, chest pain, repeated pneumothorax and body weight loss. Chest CT scan demonstrated irregular thickening of the pleura in bilateral upper lungs. Pathological manifestations consisted of evident thickening of the visceral pleura, fibroelastosis and arrangement disorder in the pleura and the underlying pulmonary interstitium. PPFE could progress rapidly. Adrenocortical hormone and other immunosuppressive agents yielded low clinical efficacy and poor clinical prognosis. Lung transplantation was a necessary treatment for PPFE. Conclusions PPFE cannot be effectively treated by conservative therapy. It is recommended to deliver lung transplantation as early as possible.
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Objective To explore the effect of lung strain on breathing mechanics in dogs with acute respiratory distress syndrome (ARDS).Methods Twenty-four healthy male Beagle dogs were recruited to reproduce medium ARDS models with venous injection of 0.18 mL/kg oleic acid, and they were randomly assigned to five groups with random numbers table method. In lung protective ventilation (LPV) group (n = 4), the ventilation was supported for 24 hours with tidal volume (VT) at 6-8 mL/kg, and in lung strain 1.0, 1.5, 2.0, 2.5 groups (S1.0, S1.5, S2.0, S2.5 groups), the VT was calculated from lung strain, the volume recruitment by positive end expiratory pressure (VPEEP) and functional residual capacity (FRC). Five groups were given mechanical ventilation for 24 hours or until reaching the end point of the experiment [when the dosage of norepinephrine was higher than 1.4μg·kg-1·min-1, the blood pressure was still lower than 60 mmHg (1 mmHg = 0.133 kPa) for more than 30 minutes, which was regarded as the end point of the experiment]. Static lung compliance (Cst), airway plateau pressure (Pplat) and lung stress during the experiment were recorded. Linear regression analysis was used to fit the regression equations of lung strain and Cst descending rate,Pplat and lung stress for analyzing their relationships.Results The VT of group LPV was (7.1±0.5) mL/kg. With the increase of lung strain, VT was gradually increased. VT of group S1.0 [(7.3±1.8) mL/kg] was similar to group LPV. VT of groups S1.5, S2.0, S2.5 was significantly higher than that of group LPV (mL/kg: 13.3±5.5, 18.7±5.4, 20.1±7.4 vs. 7.1±0.5, allP < 0.05). Moreover, under the same lung strain, the difference in VT among individuals was large. The Cst of each group was decreased significantly at the end of the experiment as compared with that before model reproduction. With the increase of lung strain, the rate of Cst descending was increased, Cst dropped more significantly in groups S2.0 and S2.5 than that in groups S1.0 and S1.5 [(48.0±15.0)％, (54.4±9.5)％ vs. (25.9±13.7)％, (38.6±8.1)％, all P < 0.05]. Pplat and pulmonary stress at model reproduction in all groups were significantly higher than those before model reproduction, and they increased with the prolongation of ventilation time. Pplat and lung stress at 4 hours of ventilation in group S1.5 were significantly higher than those in group LPV [Pplat (cmH2O, 1 cmH2O = 0.098 kPa):26.2±2.3 vs. 20.2±4.2, lung stress (cmH2O): 20.5±2.0 vs. 16.6±2.5, bothP < 0.05], and they increased with lung strain increasing till to the end of experiment. It was shown by correlation analysis that lung strain was positively related with Cst descending rate, Pplat and lung stress at 4 hours of ventilation (rvalue was 0.716, 0.660, 0.539, respectively, allP < 0.05), which indicated a strong linear correlation. It was shown by fitting linear regression analysis that when lung strain increased by 1, Cst descending rate increased by 19.0％ [95％ confidence interval (95％CI) = 14.6-23.3, P = 0.000], Pplat increased by 10.8 cmH2O (95％CI = 7.9-13.7,P = 0.002), and the lung stress increased by 7.4 cmH2O (95％CI = 4.7-10.2,P = 0.002).Conclusion In animal ARDS models, the larger the lung strain, the higher the Pplat and lung stress during mechanical ventilation, VT originated for lung strain 2.0 and 2.5 may further reduce Cst in ARDS models, when lung strain over 1.5, Pplat and lung stress increased significantly, which exceeded the safe range of LPV (35 cmH2O and 25 cmH2O, respectively), and further aggravated ventilator induced lung injury (VILI).
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Objective To explore the association of serum and sputum desmosine with treatment response in patients with chronic obstructive pulmonary disease(COPD). Methods Serum and induced sputum desmosine were measured with enzyme linked immunosorbent assay in 65 patients with newly diagnosed COPD and 26 healthy people. The associations of desmosine with pulmonary function ,modified Medical Research Council dyspnea scale(mMRC),and St. George's Respiratory Questionnaire score(SGRQ)were analyzed before and after treat-ment with inhaled corticosteroid/long acting β2-agonist. The relationship between desmosine and treatment re-sponse in COPD were explored. Results Level of sputum desmosine was higher in patients with COPD than in healthy controls(1061.2 ± 933.9 ng/mL vs. 443.5 ± 501.7 ng/mL;t=2.277,P=0.027). Sputum desmosine level was negatively related with forced expiratory volume in 1 second(FEV1)(r=-0.357,P=0.001)and forced vital capacity(FVC)(r =-0.479,P = 0.02). Serum desmosine level was correlated with pulmonary function,MRC, and SGRQ(P>0.05 for all comparisons). 3 months after treatment,neither serum nor sputum desmosine declined significantly(P>0.05). FVC,MRC,and the total scores and activity scores on the SGRQ improved more markedly in patients with lower expression of sputum desmosine than in those with higher expression(P < 0.05 for all com-parisons). Conclusions Level of sputum desmosine is inversely correlated with pulmonary function in stable COPD. Patients with lower expression of sputum desmosine have more significant improvement in symptoms.
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Objective To evaluate the effect of noninvasive ventilation (NIV) on hypercapnic encephalopathy syndrome (HES) induced by acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods An extensive search of related literature from the PubMed, EMBASE, Cochrane library, CNKI and Wanfang databases up to January 2015 was performed. Randomized controlled trials (RCTs) and case control studies regarding comparison of the effect of NIV and conventional mechanical ventilation (CMV) on the HES were collected. Critical appraisal skills program (CASP) was adopted to assess the quality of the studies. Data including mortality, trachea intubation rate, duration of mechanical ventilation and complication rate were collected, and Meta-analysis was performed by RevMan 5.3. Results Finally, 6 studies were included with 225 subjects, among whom 112 were in NIV group and 113 in CMV group, and the average Kelly-Matthay score was 3. Compared with CMV group, the mortality [20.5% (23/112) vs. 32.7% (37/113), risk ratio (RR) = 0.63, 95% confidential interval (95%CI) = 0.40-0.98, P = 0.04], intubation rate [35.7% (40/112) vs. 100.0% (113/113), RR = 0.38, 95%CI = 0.26-0.55, P < 0.000 01], incidence of ventilation related complications [26.2% (21/80) vs. 50.6% (42/83), RR = 0.52, 95%CI = 0.34-0.79, P = 0.002] in NIV group were significantly decreased, and the duration of mechanical ventilation was significantly shortened [days: 7.1 vs. 16.2, standard mean difference (SMD) = -0.93, 95%CI = -1.39 to -0.46, P < 0.000 1]. Conclusion NIV could significantly lower the mortality rate, intubation rate, and complications in the treatment of HES induced by AECOPD under close monitoring.
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Objective To study the chronic toxicity and its severity of a Chinese medicine, Anshen Bunao Liquid ( ABL) , in rats, provide the target organs and extent of reversibility of their adverse effects, determine its non-toxic dose, and to evaluate the safety of medication and provide reference for clinical trial dose and observation indexes.Methods Two hundred and forty healthy 6-week old Wistar rats ( male:female=1:1) were divided into low,middle, and high dose Anshen Bunao liquid groups (2.5, 5, 10 mL/kg),and solvent control group (distilled water 2 mL/100 g), with 60 rats in each group.The drug was orally administered to rats once a day and 6 days per week for 26 weeks.The general state, body mass and food intake were measured.By the end of 13 weeks, 26 weeks of experiment and 4-week recovery period after drug withdrawal, hematological and biochemical indexes were assayed, organ coefficients were determined, and histopathological observation was performed.Results Long-term continuous oral administration of Anshen Bunao liquid, the general state, behavior and gross appearance showed no significant abnormal changes.Compared with the control group, no significant differences in all checked items were found in the treatment groups.During 3 and 6 months, the size and location of organs,organ weight and organ coefficient had no obvious changes, with only non-significant increase of weight of some organs.All the organ coefficients of the animals in different groups were within normal range.Histopathology showed no obvious patho-logical and toxicological changes even in the high-dose drug treatment group, and no delayed toxicity occurred after with-drawal of drug administration.Conclusions The Chinese drug, Anshen Bunao liquid has no obvious toxicity and no de-layed toxicity after withdrawal of the drug in rats.It is expected that the planned dose in clinical use is a safe dose.
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Objective To better understanding the clinical presentations of phaeohyphomycosis,and improve the diagnosis and management of the disease.Methods We reported a case of pulmonary phaeohyphomycosis caused by Exophiala jeanselmei at the First Affiliated Hospital of Guangzhou Medical University in 2008,and reviewed the relevant literature.The clinical,radio-logical and etiological features were summarized based on this case and the other 23 phaeohyphomycosis patients reported in China from January 1995 to August 2013.Results 24 Chinese cases of phaeohyphomycosis have been reported to date,including 15 males and 9 females.The age of these patients ranged from 4 to 76 (mean 40.0±21 .8)years old.Seventeen patients were otherwise healthy.The other 7 patients had complications.Clinical presentations of phaeohyphomycosis vary widely,including cutaneous and subcutaneous infection in 18 cases,pulmonary and central nervous system involvement in two cases each,para-nasal sinus and palpebral conjunctiva infection one case each.The diagnosis of 18 cases were confirmed both microbiologically and histologically.One case was confirmed histologically alone.Five cases were identified microbiologically alone.The samples for culture were collected from skin abscess (1/5 ),pulmonary tissue (2/5 ),and cervical spinal fluid (2/5 ),respectively. Twenty-two strains of causative organisms were identified,7 of which were Exophiala jeanselmei .Twenty-three patients received treatment.They were cured by antifungal agents alone (18)or in conjunction with surgical resection (4 ),or assisted with XD-635AB-based photodynamic laser therapy (1).Specifically,10 pa-tients were cured by itraconazole alone.Conclusions In China, most patients of phaeohyphomycosis have concurrent conditions or have previously received immunosuppressive agents and cor-ticosteroids.Cutaneous and subcutaneous infection were most common,located mainly on limbs,face,chest and abdominal skin.The most frequently isolated pathogen is Exophiala jeanselmei ,followed by Phialophora verrucosa and Exophiala spinifera .Itraconazole therapy would be very effective.Susceptibility testing is very useful in case of refractory infection.
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Objective Backgrounds and Objectives Skeletal muscle dysfunction is an important systemic manifestation of several diseases such as chronic obstructive pulmonary disease and chronic heart failure.Quadriceps function assessment was used in majority of the studies for assessment of peripheral skeletal muscle function as it is readily accessible and is a primary locomotor muscle.Appropriate evaluation of the prevalence and severity of quadriceps dysfunction relies on the proper control data from the age-matched normal subject.So,the present study was aimed to measure the quadriceps function in healthy elderly,to investigate the multiple factors related to quadriceps functions,and to establish the normal ranges for quadriceps functional performance in healthy elderly.Methods Sixty healthy volunteers were recruited for the study.Quadriceps function was assessed by measurement of the following 3 items:maximum of twitch tension (TwQmax) induced by magnetic stimulation of femoral nerve,maximal volitional contraction (QMVC),and endurance time.The intensity and frequency of quadriceps exercises were quantified with physical activity (PA) scores by using a special PA questionnaire.Anthropometric measurements such as height,weight and mid-thigh muscle mass (MTMC) were measured in all of the subjects.Multiple regression models were developed by stepwise method to determine the independent factors respectively contributing to the quadriceps functional performance.Results Quadriceps functional tests results showed that the data of the three items fit normal distributions in both female and male subjects,and the gendcr-related difference was observed in quadriceps strength,with TwQmax and QMVC being significantly decreased in female than in male subjects.The mean values and normal ranges for TwQmax,QMVC,and endurance time were [13.86(10.53-17.65)] kg,[42.06(34.45-49.67)] kg,and [81.08(58.52-103.66)] second,respectively,in male subjects; and they were [7.41(6.02-9.52)] kg,and [29.40(24.66-33.82)] kg,and [83.44 (60.81-106.67)] second,respectively,in female subjects.Stepwise regression correlation analysis showed that QMVC was related with sex,PA scores and weight (R2=0.61,P＜0.01) ; endurance time was predicted by PA scores,MTMC,body weight and sex (R2 =0.58,P ＜0.01) ; and TwQmax was predicted by sex,height and PA scores (R2 =0.67,P＜0.01).Conclusions Our study results demonstrate that quadriceps functional performance fits normal distributions in healthy elderly,and that quadriceps function is related to multiple factors such as subjects' sex,muscles exercises,weight,height,muscle mass,and etc,with muscles exercises being the most significant one,except of gender.We conclude that muscles exercises take a very important role in muscles functional performance in healthy elderly.
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<p><b>OBJECTIVE</b>Through the paired comparison on the toxicity effect of Aconiti Lateralis Radix Praeparata of different compatibility proportion of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma, to observe the detoxication effect of Glycyrrhizae Radix et Rhizoma to Aconiti Lateralis Radix Praeparata.</p><p><b>METHOD</b>Paired comparison on the mouse acute toxicity of Aconiti Lateralis Radix Praeparata and Aconiti Lateralis Radix Praeparata with different compatibility proportion of Glycyrrhizae Radix et Rhizoma, to assay the LD50. Paired comparison on the rat heart toxicity of Aconiti Lateralis Radix Praeparata and Aconiti Lateralis Radix Praeparata with different compatibility proportion of Glycyrrhizae Radix et Rhizoma, to assay the TD50. We dilute medicated serum of Aconiti Lateralis Radix Praeparata, Aconiti Lateralis Radix Praeparata plus Glycyrrhizae Radix et Rhizoma (3:1), Aconiti Lateralis Radix Praeparata plus Glycyrrhizae Radix et Rhizoma (1: 1) into 5%, 10%, 20% solution with serum free DMEM, to survey the effect of different concentration of medicated serum to the pulsing rhythm of myocardial cell of original generation newborn rat, cell surviva rate and content of LDH in myocardial cells.</p><p><b>RESULT</b>LD50 and TD50 of Aconiti Lateralis Radix Praeparata can be increased after adding Glycyrrhizae Radix et Rhizoma Compared to the blank serum, medicated serum with Aconiti Lateralis Radix Praeparata can obviously increased the pulse rhythm of myocardial cell and the content of LDH (P < 0.05). The medicated serum with Aconiti Lateralis Radix Praeparata added different proportion of Glycyrrhizae Radix et Rhizoma can reduce the acceleration of myocardial cell's rhythm, which is induced by Aconiti Lateralis Radix Praeparata, and can reduce the content of LDH. With the increased ratio of Glycyrrhizae Radix et Rhizoma, the effect is stronger. But for the serum with different concerntration of Aconiti Lateralis Radix Praeparata or Aconiti Lateralis Radix Praeparata added Glycyrrhizae Radix et Rhizoma, there is no obvious effect to the cell survival.</p><p><b>CONCLUSION</b>Glycyrrhizae Radix et Rhizoma has the detoxication effect through increasing the ultimatetotaldosage of Aconiti Lateralis Radix Praeparata. The detoxication effect of Glycyrrhizae Radix et Rhizoma to Aconiti Lateralis Radix Praeparata is through restraining the increased rhythm of myocardial cell and protecting the myocardial cell.</p>
Subject(s)
Animals , Female , Male , Mice , Rats , Aconitum , Chemistry , Cells, Cultured , Chemistry, Pharmaceutical , Methods , Drug Interactions , Drugs, Chinese Herbal , Pharmacokinetics , Toxicity , Glycyrrhiza , Chemistry , Inactivation, Metabolic , Mice, Inbred ICR , Myocytes, Cardiac , Metabolism , Rats, Sprague-Dawley , Rhizome , ChemistryABSTRACT
Objective To investigate the prevalence and severity of malnutrition in patients with stable chronic obstructive pulmonary disease (COPD) , analyze serum levels of myostatin, tumor necrosis factor alpha (TNFα) and C reactive protein (CRP) , and investigate the relationship between serum myostatin and malnutrition in COPD. Methods Seventy-one patients with stable COPD and 60 age-matched healthy volunteers were recruited in this study. Pulmonary function was tested in all of the subjects and the severity of malnutrition was evaluated by a multiple-parameter malnutritional index (MNI). Based on the MNI scores, patients with COPD were divided into group Ⅰ (MNI≥5 score) and group Ⅱ (MNI ＜ 5 score) , the former represents the patients with severe or very severe malnutrition while the latter represents the patients with mild or without malnutrition. Serum concentration of myostatin, TNFα and CRP were measured by enzyme-linked immunosorbent assay. Results The MNI score was significantly elevated in patients with COPD [(7. 75 ±3. 86)score] compared with the controls [(1. 13 ±0. 96)score; P＜0.001],and 55 patients (77%) in COPD group Ⅰ showed MNI ≥ 5 (9. 30 ± 3. 01) score. Serum myostatin concentration was significantly elevated in COPD group Ⅰ [(12. 18 ±4. 76)μg/L] than in COPD group Ⅱ [(9. 73 ±2.85) μgL] and controls [(7.93 ±2.35) μg/L], with each P ＜ 0.001. Serum TNFα concentration was also significantly elevated in patients with COPD compared with the controls (P ＜ 0. 001).Pearson correlation analysis showed that serum myostatin levels were significantly correlated with MNI scores (r = 0. 438, P - 0. 000) and TNFa levels (r = 0. 234, P = 0. 041) in COPD group (combined group I and Ⅱ) while MNI scores were correlated inversely with BMI in COPD group (r = - 0. 530, P = 0. 000) . After stratified with subgroups, the correlation between myostatin levels and MNI scores was more significant and the correlation coefficient was higher (r =0.464, P =0.000) in COPD group I patients. Moreover,myostatin levels were inversely correlated with BMI (r = - 0. 287, P = 0. 034) and forced expiratory volume in one second of the predicted value (r = - 0. 264, P = 0. 049) in COPD group I patients. Conclusions Malnutrition commonly and substantially exists in patients with COPD; serum myostatin concentration is significantly elevated and is correlated with the severity of malnutrition in the patients. The elevation of serum myostatin may contribute to malnutrition in COPD patients.
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Objective To explore the relationship between improved exercise endurance and inspiratory muscle strength,dyspnea and lower limb fatigue in chronic obstructive pulmonary disease(COPD)patients. Methods Twelve moderate-to-severe COPD patients were given lower limb exercise training for 12 weeks.Routine tests of pulmonary ventilation function,diffusion function,lung volume,maximal inspiratory pressure(MIP),expiratory flow limitation(EFL),cycle ergometer exercise capacity and constant work rate capacity were administered before and after the training program.Borg's scale(BS)was used to assess dyspnea and lower limb fatigue was measured during the exercise tests.Results After training,the average peak work rate(W Rpeak)and average MIP both had increased significantly,but no significant change was observed in routine pulmonary ventilation function,diffusion function or lung volume.The 5-point EFL score showed no significant change.hut Borg's scale dyspnea scores and lower limb fatigue decreased significantly.The changes in W Rpeak were positively correlated with the MIP changes,Borg scale scores and changes in Borg scores.All of these relationships were statistically significant. Conclusion The improved exercise endurance of moderate-to-severe COPD patients after lower limb exercise training is due to increased inspiratory muscle strength and decreases in the sensation of dyspnea and lower limb fatigue.