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Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.
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ObjectiveTo investigate the clinical features and maternal and fetal outcomes of acute pancreatitis in pregnancy （APIP） and the risk factors for disease aggravation， and to establish a predictive model. MethodsA retrospective analysis was performed for 52 APIP patients who were admitted to Affiliated Hospital of Zunyi Medical University from January 2017 to December 2022， and according to disease severity， they were divided into mild acute pancreatitis （MAP） group with 32 patients， moderate-severe acute pancreatitis （MSAP） group with 8 patients， and severe acute pancreatitis （SAP） group with 12 patients. The logistic regression analysis was performed for the clinical data of each group，and the receiver operating characteristic （ROC） curves were plotted to assess the value of risk factors in predicting the severity of APIP. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups，and the least significant difference t-test was used for further comparision between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups，and the Wilcoxon rank-sum test was used for further comparision between two groups； the chi-square test was used for comparison of categorical data between groups. ResultsOf all patients in terms of etiology， 26 （50%） had hyperlipidemic pancreatitis， 20 （38.4%） had biliary pancreatitis， and 6 （11.5%） had idiopathic pancreatitis. In terms of gestational week， 1 patient （1.9%） was in early pregnancy， 25 （48.1%） were in mid-pregnancy， and 26 （50.0%） were in late pregnancy. A total of 10 patients （19.2%） had acute respiratory distress syndrome （ARDS）， among whom 9 （90%） required respiratory support. There were significant differences between the patients with different severities of APIP in aspartate aminotransferase， alanine aminotransferase， blood urea nitrogen， blood glucose， C-reactive protein （CRP）， international normalized ratio （INR）， pneumonia， ARDS， sepsis， hepatic insufficiency， and coagulation dysfunction （all P<0.05）. The univariate analysis showed that the severity of APIP was associated with blood glucose， blood urea nitrogen， CRP， and pneumonia （all P<0.05）， and pneumonia was a risk factor for the aggravation of APIP （odds ratio=18.938， 95% confidence interval： 1.020 — 351.747， P=0.048）. CRP， blood glucose， blood urea nitrogen， and INR used in combination had a larger area under the ROC curve than each index used alone （0.954 vs 0.778/0.796/0.721/0.801）. ConclusionPneumonia is a risk factor for the aggravation of APIP， and the combination of CRP， blood glucose， blood urea nitrogen， and INR can be used to predict the severity of APIP.
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OBJECTIVE@#To investigate the effect of hyperoxia on intestinal metabolomics in mice.@*METHODS@#Sixteen 8-week-old male C57BL/6 mice were randomly divided into hyperoxia group and control group, with 8 mice in each group. The hyperoxia group was exposed to 80% oxygen for 14 days. Mice were anesthetized and euthanized, and cecal contents were collected for untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) combined detection. Orthogonal partial least square discriminant analysis (OPLS-DA), volcano plot analysis, heat map analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the effects of hyperoxia on metabolism.@*RESULTS@#(1) OPLS-DA analysis showed that R2Y was 0.967 and Q2 was 0.796, indicating that the model was reliable. (2) Volcano plot and heat map analysis showed significant statistical differences in the expression levels of metabolites between the two groups, with 541 up-regulated metabolites, 64 down-regulated metabolites, and 907 no differences, while the elevated 5-hydroxy-L-lysine was the most significant differential metabolite induced by high oxygen. (3) KEGG pathway enrichment analysis showed that porphyrin and chlorophyll metabolism (P = 0.005), lysine degradation (P = 0.047), and aromatic compound degradation (P = 0.024) were the targets affected by hyperoxia. (4) Differential analysis of metabolic products through KEGG enrichment pathway showed that hyperoxia had a significant impact on the metabolism of porphyrin and chlorophyll, lysine, and aromatic compounds such as benzene and o-cresol.@*CONCLUSIONS@#Hyperoxia significantly induces intestinal metabolic disorders. Hyperoxia enhances the metabolism of porphyrins and chlorophyll, inhibits the degradation of lysine, and delays the degradation of aromatic compounds such as benzene and o-cresol.
الموضوعات
Mice , Male , Animals , Lysine , Hyperoxia , Benzene , Mice, Inbred C57BL , Metabolic Diseases , Oxygen , Chlorophyll , Porphyrins , Biomarkers/metabolismالملخص
Objective:To investigate the clinical characteristics and treatment of patients with refractory spasm tetanus.Methods:Tetanus patients admitted to the Affiliated Hospital of Zunyi Medical University from January 2011 to April 2021 were collected and divided into the refractory spasm group and general group according to whether they were refractory spasm. The general demographic characteristics, clinical characteristics, treatment and prognosis of the two groups were compared. The treatment and risk predictors of patients with refractory spasm tetanus were explored.Results:Among the 59 tetanus patients, 35 patients (59.32%) were in the refractory spasm group and 24 patients (40.68%) were in the general group. There were no significant differences in sex, age, latency and trauma site between the two groups ( P>0.05). All patients with refractory spasmodic tetanus were treated with mechanical ventilation, the length of hospital stay was significantly prolonged, and the rate of pulmonary infection was significantly increased ( P<0.05). The incidence of multiple sites muscular rigidity (spasm/limb stiffness, neck stiffness, and angular pedicle tension) in patients with refractory spasmodic on the first day of admission was higher than that in the general group ( P<0.05). The patients' initial symptoms (within 24 h after admission) were muscle spasm/limb stiffness + neck stiffness + angular pedicle inversion, which had the highest specificity for predicting the occurrence of refractory spasm. The proportion of Ablett grade Ⅳ in patients with refractory spasm was higher than that in the general group, and the difference was statistically significant ( P<0.05). The 48.75% patients with refractory spasm tetanus were treated with more than 3 sedatives combined with muscle relaxants, and the duration of sedative use was significantly prolonged ( P<0.05). Conclusions:The mechanical ventilation time and hospitalization time in tetanus patients with refractory spasm are significantly prolonged, and the incidence of pulmonary infection is significantly increased, which requires the combined application of a large number of sedative and muscle relaxants for a long time, and the incidence of refractory spasm is higher in patients with multi-site muscular rigidity at the early stage of the disease.
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Objective:To explore the risk factors of abdominal hemorrhage (AH) in patients with severe acute pancreatitis (SAP) and its impact on outcome.Methods:The clinical data of 231 SAP patients admitted to Diagnosis and Treatment Center for SAP of Guizhou Province from January 1, 2015 to December 31, 2019 were retrospectively analyzed. These patients were divided into AH group and non-AH group. The general information, etiology, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, organ failure, complications, interventions, bleeding time, bleeding site and outcome were compared between the two groups. Binary multivariate Logistic regression analysis was used to explore the risk factors of AH in SAP patients and whether the time and location of AH were risk factors affecting the outcome.Results:A total of 231 patients were enrolled in the analysis, including 198 patients without AH and 33 with AH (14.3%). There was no significant difference in gender, age or etiology between the two groups. The scores of APACHE Ⅱ and SOFA in AH group were significantly higher than those in non-AH group [APACHE Ⅱ score: 18 (12, 24) vs. 13 (9, 19), SOFA score: 9 (5, 15) vs. 5 (4, 11), both P < 0.01]. The incidences of acute kidney injury (AKI), gastrointestinal dysfunction, coagulation disorders, necrotic infection, pseudocyst and gastrointestinal fistula in AH group were significantly higher than those in non-AH group (66.7% vs. 47.0%, 36.4% vs. 7.1%, 18.2% vs. 6.6%, 66.7% vs. 9.1%, 66.7% vs. 34.3%, 9.1% vs. 1.5%, all P < 0.05). The proportions of requiring mechanical ventilation (MV) and surgical intervention in AH group were significantly higher than those in non-AH group (69.7% vs. 43.4, 48.5% vs. 14.6%, both P < 0.01). The length of intensive care unit (ICU) stay and hospital stay in AH group were significantly longer than those in non-AH group [length of ICU stay (days): 13 (8, 19) vs. 7 (3, 16), length of hospital stay: 24 (13, 40) vs. 17 (12, 24), both P < 0.01], and the hospital mortality was significantly higher (60.6% vs. 9.6%, P < 0.01). Multivariate Logistic regression analysis showed that APACHE Ⅱ score [odds ratio ( OR) = 1.157, 95% confidence interval (95% CI) was 1.030-1.299, P = 0.014], infectious necrosis ( OR = 12.211, 95% CI was 4.063-36.697, P < 0.01), pseudocyst ( OR = 3.568, 95% CI was 1.238-10.283, P = 0.019) and requiring MV ( OR = 0.089, 95% CI was 1.354-6.625, P = 0.007) were the risk factors of AH in SAP patients. In 33 AH patients, there was no significant difference in hospital mortality between early hemorrhage (occurred within 2 weeks of onset) and late hemorrhage (occurred 2 weeks after onset) groups [66.7% (8/12) vs. 57.1% (12/21), P > 0.05]. All 4 patients in the unspecified bleeding site group died during hospitalization; half or more patients died in the pseudocyst/abscess bleeding (14 cases), mesenteric/intestinal bleeding (13 cases) and gastric variceal bleeding (2 cases) groups (7 cases, 8 cases and 1 case respectively), and there were significant differences among the groups ( P < 0.05). Multivariate Logistic regression analysis showed that neither bleeding time ( OR = 0.989, 95% CI was 0.951-1.028, P = 0.574) nor bleeding site ( OR = 2.009, 95% CI was 0.822-4.907, P = 0.126) was the risk factor of death in patients with SAP combined with AH. Conclusions:Both early and late bleeding significantly increased the length of hospital stay and mortality of SAP patients. APACHE Ⅱ score, infectious necrosis and pseudocyst were the risk factors of AH in SAP patients. Neither bleeding time nor bleeding site was the risk factors of death in patients with SAP combined with AH. However, it still needed to be confirmed by a large sample clinical study.
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Mitochondrial unfolded protein response (UPR mt) is a protein-toxic stress response, which regulates the communication from mitochondria to the nucleus. It is activated when a large number of unfolded or misfolded proteins accumulate in the mitochondria. The activation of UPR mt increases the expression of a series of chaperones and proteases, and maintains the homeostasis and function of mitochondrial proteins. Mitochondria play an important role in maintaining cardiomyocyte homeostasis. The damage of myocardial mitochondria leads to the metabolic disorder of cells suffering from ischemia/reperfusion injury. It is the key mechanism of myocardial cell death. This article mainly reviews the regulatory pathway of UPR mt and the research progress of UPR mt in myocardial ischemia/reperfusion injury (MIRI), in order to provide new ideas for the treatment of MIRI.
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The Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021 (2021 guideline) was recently released. The guidelines summarized the evidences from literatures through to July 2019, and composed by 6 parts as "screening and early treatment", "infection", "hemodynamic management", "ventilation", "additional therapies" and "long-term outcomes and goals of care" with a total of 93 items and 99 recommendations. Compared with the 2016 guideline (96 recommendations), although the total number of recommendations in the 2021 guideline is similar, the number of "strong recommendations (recommend)" in 2021 guideline has dropped significantly, while as the number of "weak recommendations (suggest)" has increased significantly, and the level of the quality of evidence on which the recommendations are based has been significantly lowered. Furthermore, 2021 guideline has also markedly deleted or simplified the recommendations regarding infection prevention, acute respiratory distress syndrome (ARDS) treatment, nutritional support and so on. While, the most obvious improvement appears in the segment of "long-term outcomes and goals of care", in which the patients and their families could get help in term of determining their physical rehabilitation and discharge follow-up plans and formulating exact goals of care. 2021 guideline did not adopt new and emerging therapies or treatments, such as metagenomic next-generation sequencing (mNGS), diaphragm protective ventilation, timing of initiating renal replacement therapy for acute kidney injury, early mobility, endotoxin adsorption, tranexamic acid, E-medicine and telemedicine, big data & artificial intelligence and other new therapies. Collectively, it may suggest the 2021 guideline tend to be conservative and simplified rather than fairly optimized and logicalized, which may arouse controversy in the future and affect clinician compliance.
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Objective:To evaluate the superior effect of thoracic epidural block (TEB) used for analgesia in patients with severe acute pancreatitis (SAP).Methods:Fifty patients of both sexes, aged 18-64 yr, with SAP, with Japanese severity score (JSS) ≥3, onset time of SAP≤12 h, were divided into conventional analgesia group (group C) and TEB group.Sufentanil was intravenously infused for analgesia in group C. TEB was performed for analgesia in group TEB.In group C, sufentanil was intravenously infused at a rate of 0.2-0.3 μg·kg -1·h -1 after admission to hospital.In group TEB, an epidural catheter was placed at T 9, 10 interspace, and 0.66% lidocaine mixed with 0.33% ropivacaine was epidurally infused at a rate of 3-5 ml/h for 120 h after admission to hospital.Visual analog scale (VAS) score and intra-abdominal pressure (IAP) were recorded at 1, 24, 48, 72 and 120 h of analgesia.HR, respiratory rate (RR), oxygenation index, computed tomography severity index (CTSI), JSS and Ranson scores were recorded at 24, 72 and 120 h of analgesia, and the de-criticalization within 72 h following analgesia was evaluated. Results:Compared with group C, VAS score and IAP were significantly deceased at each time point ( P<0.05), the rate of de-criticalization (60%/90%) was increased ( P<0.05), and Ranson score, CTSI score and JSS score were decreased at 120 h of analgesia in group TEB ( P<0.05). Conclusion:TEB can not only produce good analgesic effect, but also improve the development of the disease, which has superior effect compared with routine analgesia when used for the treatment of SAP.
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The cause and treatment of refractory hyperglycemia in a critically ill coronavirus disease 2019 (COVID-19) patient during treatment were analyzed retrospectively, indicating that novel coronavirus infection may cause damage to glucose metabolism, so the monitoring and control of blood glucose should be strengthened in clinical treatment.
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Objective:To analyze the brain function of patients with delirium in intensive care unit (ICU) using resting-state functional magnetic resonance imaging (fMRI), further analyze the structural changes in the brain using diffusion tensor imaging (DTI), and explore the correlations of brain function with structural changes in patients with delirium in ICU from a new perspective of functional imaging, provide visual evidence for the diagnosis of delirium.Methods:Patients with delirium admitted to ICU of the Affiliated Hospital of Zunyi Medical University from January 1st to December 31st in 2017 were enrolled as subjects. During the same period, the healthy volunteers who matched the gender, age and education level of the patients with delirium were enrolled as control group. The intensive care delirium screening checklist (ICDSC) scores within 24 hours after ICU admission were recorded. All the subjects were scanned by fMRI and DTI. The abnormal changes in resting-state brain function of the patients with delirium were evaluated by cerebral regional homogeneity (ReHo) data analysis. The DTI data were processed by the FSL software, and the fractional anisotropy (FA) and mean diffusivity (MD) of the brain were extracted, respectively, to evaluate the damage to brain structure. The values of ReHo, FA and MD were compared between the two groups. The ReHo value of brain region with reduced ReHo value of patients with delirium as compared with the healthy volunteers was extracted for Pearson correlation analysis with ICDSC scores.Results:A total of 22 patients with delirium were included. Seven patients who did not cooperate in the examination, used sedatives or had false images in scanning, were excluded. Finally, 15 patients were enrolled in the delirium group, and 15 healthy volunteers in the healthy control group. ① No statistically significant difference was found in gender, age or education time between the two groups. ICDSC score of the delirium group was significantly higher than that of the healthy control group (6.07±1.28 vs. 1.07±0.88, P < 0.01). ② fMRI scanning and analysis results: compared with the healthy control group, the ReHo values of the cerebellum, right hippocampus, striatum, midbrain and pons in the delirium group were significantly increased (all P < 0.05, AlphaSim correction), while the ReHo values of bilateral superior frontal gyrus, bilateral median frontal gyrus, left inferior frontal gyrus, temporal lobe and parietal lobe were significantly lowered (all P < 0.05, AlphaSim correction). Correlation analysis showed that the ReHo value of the left superior frontal gyrus was negatively correlated with ICDSC score in the patients with delirium ( r = -0.794, P < 0.05), indicating that the changes in the functional area of the medial frontal gyrus was most closely related to delirium. ③ DTI scanning and analysis results: compared with the healthy control group, the FA values of the left cerebellum, bilateral frontal lobes, left temporal lobe, corpus callosum and left hippocampus in the delirium group were decreased significantly (all P < 0.05, AlphaSim correction), while the MD values of the medial frontal gyrus, right superior temporal gyrus, anterior cingulate gyrus, bilateral insular lobes and left caudate nucleus were enhanced significantly (all P < 0.05, AlphaSim correction), suggesting that the structural and functional damage was found in multiple brain regions in patients with delirium. Conclusions:Multiple brain regions of patients with delirium present abnormal resting-state brain function. The abnormal resting-state brain function of the left superior frontal gyrus is closely related to the occurrence of delirium. Structural damage is found in multiple brain regions of patients with delirium. The structural changes in the frontal lobe, temporal lobe, corpus callosum, hippocampus and cerebellum and their abnormal functions can be used as preliminary imaging indexes for the diagnosis of delirium.
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Objective To investigate the effects of uncoupling protein 2 (UCP2) overexpression on mitochondrial dynamics (mitochondrial division and fusion) of sepsis myocardial injury in rats. Methods Forty male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 10): sham operation group (Sham group) using normal saline instead of transfection and simulating cecal ligation and perforation (CLP); CLP group using normal saline instead of transfection, performing CLP to induce sepsis; adeno-associated virus (AAV) group using CLP after myocardial transfection with empty virus; UCP2 overexpression group (UCP2 group) CLP was performed 3 weeks after AAV-UCP2 (1×1015 vg/L, a total of 60 μL) myocardial transfection. The rats in each group were examined by echocardiography at 24 hours after the CLP, and then the rats were sacrificed immediately to harvest myocardial tissue. Myocardial ultrastructural changes were observed under the electron microscope, the expression of regulatory proteins related to myocardial mitochondrial dynamics [optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1) and fission 1 (Fis1)] were detected by Western Blot, and the level of mitochondrial adenosine triphosphate (ATP) production was detected by chemiluminescence. Results ①The echocardiographic results showed that there was no significant difference in left ventricular mass (LVM) and stroke volume (SV). Compared with Sham group, left ventricular diastolic anterior wall thickness (LVAWd), left ventricular systolic anterior wall thickness (LVAWs), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular systolic posterior wall thickness (LVPWs), left ventricular ejection fraction (LVEF) and left ventricular short axis shortening rate (LVFS) were significantly increased in CLP group and AAV group, while left ventricular systolic diameter (LVEDs), left ventricular diastolic diameter (LVEDd), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) were significantly decreased. Compared with CLP group and AAV group, LVAWs, LVEF, LVFS were significantly decreased in UCP2 group, and LVEDs, LVEDV and LVESV were significantly increased [LVAWs (mm): 3.82±0.42 vs. 4.34±0.30, 4.44±0.12;LVEF: 0.921±0.038 vs. 0.979±0.019, 0.991±0.010; LVFS: (65.33±6.56)% vs. (80.11±8.23)%, (85.31±6.11)%;LVEDs (mm): 1.81±0.36 vs. 0.89±0.54, 0.60±0.17; LVEDV (μL): 137.09±50.05 vs. 89.72±53.04, 85.42±40.99;LVESV (μL): 10.48±4.59 vs. 2.48±3.52, 2.58±2.50, all P < 0.05]. ② Electron microscope showed that the structure of myocardial fibers in the Sham group was clear and aligned with complete intervertebral disc and mitochondrial structure, no damage to mitochondrial membranes, and tight arrangement of cristae. In CLP group and AAV group, muscle fiber breakage, sarcoplasmic reticulum expansion, severe mitochondrial swelling and even cristage structure disorder were observed. In the UCP2 group, only myocardial fiber edema was observed, and the muscle fiber structure was more complete than that of Sham group and AAV group. The mitochondria were slightly swollen and the cristae were intact.③ Western Blot showed that there was no significant difference in the expression of Opa1 and Fis1 in the four groups. The expression of Drp1 in CLP group and AAV group were significantly higher than that in Sham group. The expression of Drp1 in UCP2 group was significantly lower than that in CLP group and AAV group (Drp1/β-actin:1.01±0.03 vs. 1.39±0.03, 1.49±0.03, both P < 0.05).④ The results of immunofluorescence showed that the ATP content of CLP group and AAV group were significantly lower than that of Sham group; the ATP content of UCP2 group was significantly higher than that of CLP group and AAV group (μmol/L: 1.99±0.15 vs. 1.10±0.17, 1.13±0.19, both P < 0.05). Conclusion UCP2 overexpression can significantly improve the systemic systolic function of myocardium in sepsis rats, protect myocardial mitochondrial ultrastructure, inhibit mitochondrial division, and improve mitochondrial ATP synthesis.
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Objective To investigate the effects of uncoupling protein 2 (UCP2) overexpression on mitochondrial dynamics (mitochondrial division and fusion) of sepsis myocardial injury in rats. Methods Forty male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 10): sham operation group (Sham group) using normal saline instead of transfection and simulating cecal ligation and perforation (CLP); CLP group using normal saline instead of transfection, performing CLP to induce sepsis; adeno-associated virus (AAV) group using CLP after myocardial transfection with empty virus; UCP2 overexpression group (UCP2 group) CLP was performed 3 weeks after AAV-UCP2 (1×1015 vg/L, a total of 60 μL) myocardial transfection. The rats in each group were examined by echocardiography at 24 hours after the CLP, and then the rats were sacrificed immediately to harvest myocardial tissue. Myocardial ultrastructural changes were observed under the electron microscope, the expression of regulatory proteins related to myocardial mitochondrial dynamics [optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1) and fission 1 (Fis1)] were detected by Western Blot, and the level of mitochondrial adenosine triphosphate (ATP) production was detected by chemiluminescence. Results ①The echocardiographic results showed that there was no significant difference in left ventricular mass (LVM) and stroke volume (SV). Compared with Sham group, left ventricular diastolic anterior wall thickness (LVAWd), left ventricular systolic anterior wall thickness (LVAWs), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular systolic posterior wall thickness (LVPWs), left ventricular ejection fraction (LVEF) and left ventricular short axis shortening rate (LVFS) were significantly increased in CLP group and AAV group, while left ventricular systolic diameter (LVEDs), left ventricular diastolic diameter (LVEDd), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) were significantly decreased. Compared with CLP group and AAV group, LVAWs, LVEF, LVFS were significantly decreased in UCP2 group, and LVEDs, LVEDV and LVESV were significantly increased [LVAWs (mm): 3.82±0.42 vs. 4.34±0.30, 4.44±0.12;LVEF: 0.921±0.038 vs. 0.979±0.019, 0.991±0.010; LVFS: (65.33±6.56)% vs. (80.11±8.23)%, (85.31±6.11)%;LVEDs (mm): 1.81±0.36 vs. 0.89±0.54, 0.60±0.17; LVEDV (μL): 137.09±50.05 vs. 89.72±53.04, 85.42±40.99;LVESV (μL): 10.48±4.59 vs. 2.48±3.52, 2.58±2.50, all P < 0.05]. ② Electron microscope showed that the structure of myocardial fibers in the Sham group was clear and aligned with complete intervertebral disc and mitochondrial structure, no damage to mitochondrial membranes, and tight arrangement of cristae. In CLP group and AAV group, muscle fiber breakage, sarcoplasmic reticulum expansion, severe mitochondrial swelling and even cristage structure disorder were observed. In the UCP2 group, only myocardial fiber edema was observed, and the muscle fiber structure was more complete than that of Sham group and AAV group. The mitochondria were slightly swollen and the cristae were intact.③ Western Blot showed that there was no significant difference in the expression of Opa1 and Fis1 in the four groups. The expression of Drp1 in CLP group and AAV group were significantly higher than that in Sham group. The expression of Drp1 in UCP2 group was significantly lower than that in CLP group and AAV group (Drp1/β-actin:1.01±0.03 vs. 1.39±0.03, 1.49±0.03, both P < 0.05).④ The results of immunofluorescence showed that the ATP content of CLP group and AAV group were significantly lower than that of Sham group; the ATP content of UCP2 group was significantly higher than that of CLP group and AAV group (μmol/L: 1.99±0.15 vs. 1.10±0.17, 1.13±0.19, both P < 0.05). Conclusion UCP2 overexpression can significantly improve the systemic systolic function of myocardium in sepsis rats, protect myocardial mitochondrial ultrastructure, inhibit mitochondrial division, and improve mitochondrial ATP synthesis.
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Objective@#To investigate the effects of uncoupling protein 2 (UCP2) overexpression on mitochondrial dynamics (mitochondrial division and fusion) of sepsis myocardial injury in rats.@*Methods@#Forty male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 10): sham operation group (Sham group) using normal saline instead of transfection and simulating cecal ligation and perforation (CLP); CLP group using normal saline instead of transfection, performing CLP to induce sepsis; adeno-associated virus (AAV) group using CLP after myocardial transfection with empty virus; UCP2 overexpression group (UCP2 group) CLP was performed 3 weeks after AAV-UCP2 (1×1015 vg/L, a total of 60 μL) myocardial transfection. The rats in each group were examined by echocardiography at 24 hours after the CLP, and then the rats were sacrificed immediately to harvest myocardial tissue. Myocardial ultrastructural changes were observed under the electron microscope, the expression of regulatory proteins related to myocardial mitochondrial dynamics [optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1) and fission 1 (Fis1)] were detected by Western Blot, and the level of mitochondrial adenosine triphosphate (ATP) production was detected by chemiluminescence.@*Results@#①The echocardiographic results showed that there was no significant difference in left ventricular mass (LVM) and stroke volume (SV). Compared with Sham group, left ventricular diastolic anterior wall thickness (LVAWd), left ventricular systolic anterior wall thickness (LVAWs), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular systolic posterior wall thickness (LVPWs), left ventricular ejection fraction (LVEF) and left ventricular short axis shortening rate (LVFS) were significantly increased in CLP group and AAV group, while left ventricular systolic diameter (LVEDs), left ventricular diastolic diameter (LVEDd), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) were significantly decreased. Compared with CLP group and AAV group, LVAWs, LVEF, LVFS were significantly decreased in UCP2 group, and LVEDs, LVEDV and LVESV were significantly increased [LVAWs (mm): 3.82±0.42 vs. 4.34±0.30, 4.44±0.12; LVEF: 0.921±0.038 vs. 0.979±0.019, 0.991±0.010; LVFS: (65.33±6.56)% vs. (80.11±8.23)%, (85.31±6.11)%; LVEDs (mm): 1.81±0.36 vs. 0.89±0.54, 0.60±0.17; LVEDV (μL): 137.09±50.05 vs. 89.72±53.04, 85.42±40.99; LVESV (μL): 10.48±4.59 vs. 2.48±3.52, 2.58±2.50, all P < 0.05]. ② Electron microscope showed that the structure of myocardial fibers in the Sham group was clear and aligned with complete intervertebral disc and mitochondrial structure, no damage to mitochondrial membranes, and tight arrangement of cristae. In CLP group and AAV group, muscle fiber breakage, sarcoplasmic reticulum expansion, severe mitochondrial swelling and even cristage structure disorder were observed. In the UCP2 group, only myocardial fiber edema was observed, and the muscle fiber structure was more complete than that of Sham group and AAV group. The mitochondria were slightly swollen and the cristae were intact.③ Western Blot showed that there was no significant difference in the expression of Opa1 and Fis1 in the four groups. The expression of Drp1 in CLP group and AAV group were significantly higher than that in Sham group. The expression of Drp1 in UCP2 group was significantly lower than that in CLP group and AAV group (Drp1/β-actin: 1.01±0.03 vs. 1.39±0.03, 1.49±0.03, both P < 0.05).④ The results of immunofluorescence showed that the ATP content of CLP group and AAV group were significantly lower than that of Sham group; the ATP content of UCP2 group was significantly higher than that of CLP group and AAV group (μmol/L: 1.99±0.15 vs. 1.10±0.17, 1.13±0.19, both P < 0.05).@*Conclusion@#UCP2 overexpression can significantly improve the systemic systolic function of myocardium in sepsis rats, protect myocardial mitochondrial ultrastructure, inhibit mitochondrial division, and improve mitochondrial ATP synthesis.
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Objective Changes of small intestine villus microcirculation perfusion in sidestream dark-field (SDF) imaging in the rabbits during endotoxic shock after fluid resuscitation with different target mean arterial pressure (MAP), and evaluation of feasibility of monitoring small intestine villus microcirculation by SDF were studied. Methods Sixty standard New Zealand white rabbits were randomly divided into two groups: low target MAP group (group A, n = 30) and high target MAP group (group B,n = 30). Fistula operation of ileum was madein vitro, and lipopolysaccharide (LPS, 2 mg/kg) was injected to establish endotoxic shock model. Group A was administered with the lower dose fluid resuscitation (lactated Ringer solution, 20 mL·kg-1·h-1) for target MAP of 65 mmHg (1 mmHg =0.133 kPa); group B was administered with the higher dose fluid resuscitation (lactated Ringer solution, 30 mL·kg-1·h-1) for MAP of 80 mmHg. Continuous norepinephrine intravenous injection (0.5-1.0μg·kg-1·min-1) was administered only after fluid therapy couldn't reach the target MAP. The changes of small intestine villus microcirculation perfusion indexes such as vessels per villus (VV), proportion of perfused villi (PPV), microvascular flow index (MFI), borders of villus score (BVS), vessels villus score (VVS) were continuously observed and recorded before the shock, during the shock and after fluid resuscitation using SDF imaging. The differences of microcirculation perfusion were compared between two groups using the specific parameter evaluation system to determine severity of villi microcirculation and injury scores at different stages.Results VV and borders of villus were clear and contact before shock in two groups. After shock, VV, PPV were significantly decreased in both two groups, the borders of villus were destroyed, MFI, BVS, VVS and the total score of villi injury microcirculation were obviously and severely decreased. Partial blood flow of villous capillaries after fluid resuscitation was recovered in two groups, but the perfusion of some region was un-balanced with the outworn borders of villus. VV were rose as compared before and after fluid resuscitation in groups A and B (vessels: 1.21±0.22 vs. 0.81±0.12, 1.54±0.28 vs. 0.79±0.13), and PPV [(31±4)% vs. (12±2)%, (38±5)% vs. (13±3)%], MFI (1.55±0.09 vs. 1.09±0.03, 1.97±0.11 vs. 1.05±0.03), VVS (points: 1.22±0.08 vs. 0.89±0.02, 2.06±0.15 vs. 0.90±0.02) and the sum of MFI, BVS, VVS (3.70±0.19 vs. 2.85±0.07, 5.01±0.29 vs. 2.88±0.08) were significant rose (allP 0.05).Conclusions For the small intestine villus microcirculation perfusion, the higher target MAP (80 mmHg) after fluid resuscitation or/and vasoconstrictor drugs usage were probably better than the relatively lower target MAP (65 mmHg) during endotoxic shock. SDF imaging is a very promising technique for intestinal villi microcirculatory visualization and assessment.
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AIM: To investigate the changes of small intestine villus and sublingual microcirculation perfusion in the rabbits during endotoxic shock by sidestream dark-field imaging (SDF) after resuscitation to a mean arterial pressure (MAP) level.METHODS: New Zealand white rabbits (n=60) were randomly divided into 2 groups (group of villus and group of sublingua).The fistula operation of ileum was performed.Lipopolysaccharide was injected to establish endotoxic shock model, and fluid resuscitation (lactated Ringer's solution, 30 mL·kg-1·h-1) was given to maitain the MAP of the animals to 80 mmHg.Continuous norepinephrine was intravenously injected at 0.5~1 μg·kg-1·min-1 only if fluid therapy did not maintain the MAP level.The changes of microcirculatory perfusion indexes in small intestine villus and sublingual tissues such as vessels per villus (VV), microvascular flow index (MFI), proportion of perfused villi (PPVi), villus border score, villus vessel score, total vessel density (TVD), perfused vessel density (PVD) and proportion of perfused vessels (PPVe) were continuously observed and recorded by SDF before shock, during shock and after fluid resuscitation.RESULTS: MFI and PPVi in small intestine villus, and MFI, PPVe, TVD and PVD in sublingual tissues were significantly decreased after shock (P<0.01).Compared with MFI in sublingual microcirculation, MFI in villus was significantly decreased (P<0.01).MFI and PPVi in small intestine villus, and MFI, PPVe, TVD and PVD in sublingual tissues were improved after recovered to the target MAP by fluid resuscitation (P<0.05).However, MFI in small intestine villus was significantly lower than that in sublingual tissues after fluid resuscitation (P<0.01).CONCLUSION: The difference between small intestine villus and sublingual microcirculation perfusion during endotoxic shock is observed.The descent degree of microcirculation perfusion in small intestine villus is larger than that in sublingual tissues after shock, and the recovery degree of small intestine villus microcirculation is lower than that of sublingual microcirculation afer fluid resuscitation.
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Objective To investigate the epidemiologic characteristics of patients with severe acute pancreatitis (SAP) and the effects of its complications on prognoses in past 7 years in the north area of Guizhou province. Methods Data of 209 patients with SAP admitted to the Department of Critical Care Medicine of Affiliated Hospital of Zunyi Medical College from January 2009 to January2016 were retrospectively analyzed, and they were divided into a survival group (178 cases) and a death group (31 cases) according to the prognosis. The gender, age, diagnosis (primary and recurrent), the length of stay in hospital, the levels of creatinine and total bilirubin (TBil), the time of blood purification, hematocrit (HCT) level on the first day after admission, pathogenesis, complications [infection, pseudocyst, intra-peritoneal hemorrhage, acute renal failure (ARF), acute respiratory distress syndrome (ARDS), abdominal compartment syndrome (ACS), pancreatic encephalopathy, multiple organ dysfunction syndrome (MODS)], sequential organ failure (SOFA) score (maximum SOFA score during hospital stay), application of hormones, surgical interference, etc. related factors were compared, the SAP epidemiological characteristics, factors affecting prognosis and the effect of complications on prognosis in intensive care unit (ICU) were analyzed in the two groups.Results Of the 209 patients 98 cases were diagnosed biliary pancreatitis accounting for the majority (46.9%), hyperlipidemic pancreatitis 76 cases (36.3%), alcoholic pancreatitis 6 cases (2.8%) and idiopathic pancreatitis29 cases (13.9%). The age (years: 47.1±13.5 vs. 53.2±12.0), creatinine (μmol/L: 109.4±100.3 vs. 335.7±222.4), the ration of intra-peritoneal hemorrhage [4.5% (8) vs. 38.7% (12)], ARF [1.1% (2) vs. 54.8% (17)], ACS [1.1% (2) vs. 9.7% (3)], MODS [18.5% (33) vs. 74.2% (23)] and SOFA score (3.3±2.4 vs. 10.5±5.4), percentage of patients using hormones [5.6% (10) vs. 29.0% (9)] were significantly lowered (allP 0.05). Logistic regression analysis showed that creatinine > 300μmol/L [odds ratio (OR) was 2.651, 95% confidence interval (95%CI) was 1.459-3.935,P = 0.017], intra-peritoneal hemorrhage (OR was 5.231, 95%CI was 3.517-7.159,P = 0.000), ARF (OR was 3.731, 95%CI was 2.641-4.857,P = 0.000), ACS (OR was 2.517, 95%CI was 1.003-3.098,P = 0.000), use of hormone (OR was 1.012, 95%CI was 0.825-2.051,P = 0.000) and SOFA score (OR was 3.179, 95%CI was 2.630-6.021 andP = 0.000), MODS (OR was 4.716, 95%CI was 2.086-7.902 andP = 0.031) were the risk factors having critical effects on the prognosis of thedisease, The higher the creatinine level, the worse the prognosis. The mortality of ARF was very high reaching 89.5%; the mortalities of patients with complications as intra-peritoneal haemorrhage, ACS, MODS, pancreatic encephalopathy, AKI, infection, pancreatic pseudocyst and ARDS were as follows: 60.0%, 60.0%, 41.1%, 33.3%, 32.1%, 23.1%, 17.7%, 13.1% respectively.Conclusion Biliary disease andhyperlipidemia are the major causes of SAP in north area of Guizhou province, creatinine > 300μmol/L, intra-peritoneal hemorrhage, ARF, ACS, SOFA score, use of hormones are the independent risk factors leading to poor outcome in patients with SAP and the use of hormones cannot ameliorate the disease situation.
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OBJECTIVE:To compare the quality control index between Jinzhen Suanzao teabag and decoction,and explore the alternative supplement of teabag to decoction. METHODS:The test sample solutions of Jinzhen Suanzao teabag and decoction were prepared by hot-maceration method and water-decoction method. The contents of water soluble extract and total flavonoids were de-termined and compared between 2 kinds of preparation. The leaching rates of teabag were investigated at different soak time(0,5, 10,15,20,25,30 min) to optimize soaking time. RESULTS:The average content of water soluble extract were 50.56% and 44.45%(P<0.05) respectively for the teabag and decoction. The total flavonoids content were 0.64 mg/g and 0.69 mg/g (P<0.05). The dissolution amount of teabag were increasing and leaching rate increased within first 20 min,and reached balance gradu-ally 25 min later. CONCLUSIONS:According to the convenience of use and results of each index,the difference in quality control index is not great between 2 kinds of preparation. Teabag can be as the supplement of decoction.
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Objective To investigate the influence of continuous veno-venous hemofiltration (CVVH) on cardiac output (CO) value and parameters of hemodynamics monitored by transpulmonary thermodilution technique in critical patients. Methods A prospective cohort study was conduced. Sixty-two critical patients admitted to intensive care unit (ICU) of Zunyi Medical College Affiliated Hospital from January 2011 to October 2015 were enrolled. All of the patients received CVVH through femoral vein puncture catheter. The CO value was monitored before CVVH operation, immediately after CVVH operation (8 ℃ normal saline was injected immediately after the output of blood from the arterial end), 5 minutes after operation, the time at the sudden interruption (press pause key after 10 minutes of operation) and resumed immediately, 15 minutes and 30 minutes after operation by pulse-indicated continuous cardiac output (PiCCO) with transpulmonary thermodilution method. The changes in heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), and blood temperature were observed at all time points. Results From CVVH before start to 5 minutes thereafter, CO values were not significantly changed in patients, fluctuating in 6.96 (7.33, 8.67)-6.98 (6.43, 7.45) L/min. When CVVH was suddenly interrupted, CO value was immediately increased to the peak 8.04 (7.36, 8.77) L/min, which showed statistically significant difference as compared with other time points (all P < 0.01). Immediately after the CVVH recovery from interruption, the CO value dropped to 4.71 (4.14, 7.26) L/min, and it was significantly lower than those at other time points (all P < 0.01). With the CVVH recovery, the patients' CO value was gradually restored to the stable operation ahead of interruption [4.71 (4.14, 7.26)-6.85 (6.08, 7.26) L/min]. During CO monitoring, HR, MAP, CVP and blood temperature of the patients were at the same level, and no significant changes were founded. Conclusions CVVH interruption of immediate PiCCO monitoring CO value were significantly increased, immediately after the CVVH recovery the CO value were significantly reduced, and the normal operation of CVVH did not affect the CO value monitoring. Hemodynamics and blood temperature of all patients were stable during CVVH.
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Objective To evaluate the effect of sedation with midazolam combined with propofol on delirium in mechanically ventilated patients in the intensive care unit (ICU).Methods Five hundred and twenty-two patients who required sedation and analgesia,endotracheal intubation and mechanical ventilation used to assist respiration,aged 28-64 yr,weighing 41-82 kg,were randomized into 2 groups according to the sedation protocols during therapy:sedation with midazolam group (group M,n =240) and sedation with midazolam + propofol group (group MP,n=232).In M and MP groups,sedation was induced with midazolam infusion 0.03-0.17 mg/min,and analgesia was induced with sufentanil infusion 0.07-0.14 μg/min.In group MP,when hemodynamics was stable,pressure support was 8-10 cmH2O,tidal volume＞400 ml,RR ＜25 bpm,and FiO2＜45％,sedation was induced with propofol infusion 0.8-2.0 mg/min instead,lasting for 12-24 h.Richmond Agitation Sedation Scale score was maintained at-1 to-2 during vcntilation.The development and duration of delirium were recorded.Delirium was divided into hyperactive delirium,hypoactive delirium and mixed delirium 3 subtypes,and the development and duration of the 3 subtypes of delirium were also recorded.Results There was no significant difference between the two groups in the incidence and duration of delirium.Compared to group M,the incidence of hyperactive delirium was significantly decreased,and no significant change was found in the incidence of hypoactive delirium and mixed delirium and the duration of the 3 subtypes of delirium in group MP.Conclusion Sedation with midazolam and propofol can decrease the development of hyperactive delirium,but can not shorten the duration of delirium in mechanically ventilated patients in the ICU.
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ObjectiveTo investigate the change in brain functional magnetic resonance imaging (fMRI)during noxious electric stimu lation of forepaw and tail in rats.MethodsForty-eight healthy SD rats of both sexes weighing 300-450 g which responded sensitively to electrical stimulation as shown by Y-maze were randomly divided into 2 groups ( n =24 each) receiving nociceptive electric stimulation of left forepaw (group LF) and tail (group T) respectively.The animals were anesthetized with intraperitoneal 10％ chloral hydrate 250-300 mg/kg.Brain fMRI was performed at 30 min after disappearance of righting reflex in both groups when electric stimulations were delivered intermittently to forepaw or tail.The images were analyzed with SPM2 software.ResultsPrimary and secondary somatosensory cortex,posterior cingutate cortex,amygdaloid nucleus and ventral posterolateral thalamic nucleus were activated in group T.Right accumbens nucleus,right primary somatosensory cortex,right ventral posterolateral thalamic nucleus and right posterior cingutate cortex were activated in group LF.ConclusionDifferent brain areas are activated by noxious electric stimulation of different parts of body as shown by brain fMRI.