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Objective:To investigate the effect of pulmonary vascular dysfunction in the prognosis of patients with acute lung injury (ALI).Methods:Patients with ALI who underwent pulmonary artery catheterization in the department of critical care medicine of Wuhan NO.1 Hospital from June 2017 to June 2019 were enrolled. The general information, clinical and hemodynamic indexes [central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), pulmonary artery systolic pressure (sPAP), pulmonary artery diastolic pressure (dPAP), mean pulmonary artery pressure (mPAP), cardiac index (CI)], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, arterial blood gas parameters [pH, partial pressure of oxygen (PO 2), partial pressure of carbon dioxide (PCO 2), oxygenation index (PaO 2/FiO 2)], whether there was shock or not; ventilator parameters [platform pressure (Plat), positive end-expiratory pressure (PEEP)], etc. were recorded. Pulmonary artery oxygen saturation, pulmonary vascular function indexes [transpulmonary potential gradient (TPG) and pulmonary vascular resistance index (PVRi)] were calculated. The relationship between TPG, PVRi and mechanical ventilation time, the length of intensive care unit (ICU) stay, cardiovascular days and 60-day mortality were analyzed in patients with different prognosis of 60-day and whether the TPG increased (≥12 mmHg was defined as elevated TPG, 1 mmHg = 0.133 kPa). Results:A total of 65 patients were included in the study, including 30 males and 35 females; aged (48.9±15.2) years old. Forty-eight cases survived in 60-days, 17 died, and the 60-day mortality was 26.2%. At the baseline, there were no significant differences in cardiopulmonary function measurements, such as CVP, sPAP, dPAP, PAWP, CI, etc. between the two groups of patients with different prognosis. The APACHEⅡ score, shock ratio, TPG and PVRi of the death group were significant higher than those of the survival group [APACHEⅡ: 34±9 vs. 28±11, shock: 52.9% vs. 25.0%, TPG (mmHg): 16.2±1.9 vs. 14.6±2.1, PVRi (kPa·s·L -1): 31.8±4.2 vs. 29.7±3.5, all P < 0.05]. The 60-day mortality of 47 patients with TPG ≥ 12 mmHg was significantly higher than that of 18 patients with TPG < 12 mmHg (34.0% vs. 5.6%), and the mechanical ventilation time and the length of ICU stay were also significantly longer (days: 17±9 vs. 11±8, 16±5 vs. 12±5), and the cardiovascular days also increased significantly (days: 23±7 vs. 18±6), and the differences were statistically significant (all P < 0.05). Pearson correlation analysis showed that PVRi was significantly correlated with mechanical ventilation time, the length of ICU stay and cardiovascular days ( r1 = 0.317, P1 = 0.030; r2 = 0.277, P2 = 0.005; r3 = 0.285, P3 = 0.002). In the individual multivariate Logistic regression model, the highest PVRi was an independent risk factor for the 60-day mortality [odds ratio ( OR) = 30.5, 95% confidence interval was 20.4-43.1, P = 0.023]. Conclusion:Pulmonary vascular dysfunction is common in ALI patients and is independently associated with adverse outcomes.
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Objective To observe the anti-inflammatory effect and opportunity of continuous blood purification (CBP) for treatment of patients with severe acute pancreatitis (SAP). Methods A retrospective study was conducted. One hundred and sixty patients with SAP admitted into the Department of Critical Care Medicine of the First Hospital of Wuhan from May 2013 to February 2017 were enrolled, and they were treated after admission by continuous vein-venous hemofiltration (CVVH) with blood flow volume 150-200 mL/min, displacement fluid velocity 2000-3500 mL/h and maintenance of ultrafiltration rate 35 mL·kg-1·h-1. According to the acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) scores in 24 hours after admission, the patients were divided into four groups: 15-19 scores (group A), 20-24 scores (group B), 25-29 scores (group C), ≥ 30 scores (group D), 40 cases in each group. Before and after treatment for 72 hours, the difference of serum adiponectin, endotoxin, tumor necrosis factor-α (TNF-α), interleukin (IL-6, IL-8) were compared, the changes of APACHE Ⅱ score, multiple organ dysfunction syndrome (MODS) score, systemic inflammatory response syndrome (SIRS) score, and also complications and mortality in 14 days after treatment were observed for the patients. Results Compared with those before CVVH treatment, the levels of endotoxin, TNF-α, IL-6, IL-8 were significantly decreased, adiponectin was significantly increased among the various APACHEⅡ score groups after CVVH treatment, and the changes of various index amplitude variations in groups B and C were more obvious [endotoxin (EU/L): 2.9±1.0 vs. 3.6±1.5, 3.1±1.2 vs. 3.8±1.4; TNF-α (μg/L): 100.5±15.3 vs. 177.5±24.6, 113.7±17.2 vs. 190.4±25.8; IL-6 (μg/L): 107.3±13.5 vs. 230.5±32.4, 118.2±16.1 vs. 244.6±30.2;IL-8 (μg/L): 201.5±25.7 vs. 355.6±47.2, 215.4±29.4 vs. 376.4±47.3; adiponectin (mg/L): 21.9±3.6 vs. 17.6±3.4, 20.8±3.7 vs. 15.8±2.9, all P < 0.05]. Compared with those before treatment, the scores of APACHEⅡ, MODS and SIRS in groups A, B and C were significantly decreased after treatment, among which the changes of the index amplitude variation of group B and group C were more significant (APACHEⅡ: 16.2±1.4 vs. 22.9±1.7, 18.2±1.4 vs. 28.3±2.1; MODS score: 4.4±1.5 vs. 7.7±1.5, all P < 0.05), the scores of APACHE Ⅱ and SIRS in group D were not significantly decreased, but on the contrary the MODS score had an increasing tendency. After treatment, the 14-day mortality was 0%, 0%, 12.5%, 47.5% in group A, B, C, D respectively (χ2 = 8.350, P = 0.039 ), and the incidence of complications was 32.5%, 52.5%, 60.0%, 80.0% after CVVH in group A, B, C, D respectively(χ2 = 27.04, P = 0.028). Conclusion Early CBP treatment can decrease the inflammatory reaction of SAP patients, and the CBP therapeutic effect is relatively good if it is carried out for SAP patients with 20 ≤ APACHE Ⅱ score < 30.
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Objective To observe the anti-inflammatory effect and opportunity of continuous blood purification (CBP) for treatment of patients with severe acute pancreatitis (SAP). Methods A retrospective study was conducted. One hundred and sixty patients with SAP admitted into the Department of Critical Care Medicine of the First Hospital of Wuhan from May 2013 to February 2017 were enrolled, and they were treated after admission by continuous vein-venous hemofiltration (CVVH) with blood flow volume 150-200 mL/min, displacement fluid velocity 2000-3500 mL/h and maintenance of ultrafiltration rate 35 mL·kg-1·h-1. According to the acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) scores in 24 hours after admission, the patients were divided into four groups: 15-19 scores (group A), 20-24 scores (group B), 25-29 scores (group C), ≥ 30 scores (group D), 40 cases in each group. Before and after treatment for 72 hours, the difference of serum adiponectin, endotoxin, tumor necrosis factor-α (TNF-α), interleukin (IL-6, IL-8) were compared, the changes of APACHE Ⅱ score, multiple organ dysfunction syndrome (MODS) score, systemic inflammatory response syndrome (SIRS) score, and also complications and mortality in 14 days after treatment were observed for the patients. Results Compared with those before CVVH treatment, the levels of endotoxin, TNF-α, IL-6, IL-8 were significantly decreased, adiponectin was significantly increased among the various APACHEⅡ score groups after CVVH treatment, and the changes of various index amplitude variations in groups B and C were more obvious [endotoxin (EU/L): 2.9±1.0 vs. 3.6±1.5, 3.1±1.2 vs. 3.8±1.4; TNF-α (μg/L): 100.5±15.3 vs. 177.5±24.6, 113.7±17.2 vs. 190.4±25.8; IL-6 (μg/L): 107.3±13.5 vs. 230.5±32.4, 118.2±16.1 vs. 244.6±30.2;IL-8 (μg/L): 201.5±25.7 vs. 355.6±47.2, 215.4±29.4 vs. 376.4±47.3; adiponectin (mg/L): 21.9±3.6 vs. 17.6±3.4, 20.8±3.7 vs. 15.8±2.9, all P < 0.05]. Compared with those before treatment, the scores of APACHEⅡ, MODS and SIRS in groups A, B and C were significantly decreased after treatment, among which the changes of the index amplitude variation of group B and group C were more significant (APACHEⅡ: 16.2±1.4 vs. 22.9±1.7, 18.2±1.4 vs. 28.3±2.1; MODS score: 4.4±1.5 vs. 7.7±1.5, all P < 0.05), the scores of APACHE Ⅱ and SIRS in group D were not significantly decreased, but on the contrary the MODS score had an increasing tendency. After treatment, the 14-day mortality was 0%, 0%, 12.5%, 47.5% in group A, B, C, D respectively (χ2 = 8.350, P = 0.039 ), and the incidence of complications was 32.5%, 52.5%, 60.0%, 80.0% after CVVH in group A, B, C, D respectively(χ2 = 27.04, P = 0.028). Conclusion Early CBP treatment can decrease the inflammatory reaction of SAP patients, and the CBP therapeutic effect is relatively good if it is carried out for SAP patients with 20 ≤ APACHE Ⅱ score < 30.
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Objective To investigate the organ protective effects and the timing of continuous blood purification (CBP) in the treatment of severe sepsis. Methods A double-blind randomized controlled trial was conducted. Seventy-four patients with severe sepsis aged between 35 years and 80 years with acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) scores over 20 admitted to Department of Critical Care Medicine of the First Hospital of Wuhan from January 2013 to January 2015 were enrolled. They were divided into control group (n = 37) and treatment group (n = 37) by random number table method. All patients in these two groups received conventional therapy following the guidelines for management of severe sepsis in 2012. In addition the patients in treatment group received continuous veno-venous hemofiltration (CVVH). The critical score, liver and kidney function indexes, etc., levels of pro-inflammatory cytokines in plasma and ultra filtrate before and 24, 48, and 72 hours after treatment, and the clinical picture 2 weeks after treatment in two groups were observed. Results APACHE Ⅱ scores, multiple organ dysfunction syndrome (MODS) scores, Murray scores of acute lung injury, and systemic inflammatory response syndrome (SIRS) scores of the patients of the above two groups were gradually declined after the treatment. The levels of white blood cell count (WBC), procalcitonin (PCT), lactate (Lac), tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-8), and endotoxin gradually lowered. Levels of blood urea nitrogen (BUN), serum creatinine (SCr), alanine transaminase (ALT) and the oxygenation index (PaO2/FiO2) showed a tendency of lowering. There were statistically significant differences in scores of critical illness, WBC, PCT, Lac, pro-inflammatory cytokine, liver and kidney function indexes, etc. between treatment group and control group 48 hours after treatment (APACHE Ⅱ score: 15.5±4.7 vs. 20.3±5.3, MODS score: 4.6±1.4 vs. 7.3±2.2, Murray score: 1.4±0.5 vs. 1.7±0.6, SIRS score: 2.9±0.8 vs. 3.7±1.0, WBC (×109/L): 1.1±0.5 vs. 1.6±0.5, PCT (μg/L): 26.7±12.0 vs. 32.4±14.1, Lac (mmol/L): 7.6±2.2 vs. 9.3±2.8, TNF-α (μg/L): 96.3±17.4 vs. 153.4±24.2, IL-6 (μg/L): 146.8±20.6 vs. 213.8±29.2, IL-8 (μg/L): 287.1±43.6 vs. 354.5±56.2, endotoxin (kEU/L): 1.4±0.5 vs. 2.6±0.8, BUN (mmol/L): 8.7±3.6 vs. 18.5±6.4, SCr (μmol/L): 143±39 vs. 197±42, ALT (U/L): 141±27 vs. 183±34, PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 150.3±45.4 vs. 124.7±32.1, all P < 0.05], and the difference was significant up to 72 hours. In the treatment group, TNF-α, IL-6, IL-8, and endotoxin could be decreased in the filtrate 24 hours and 48 hours after treatment and they correlated with the lowering tendency of their plasma levels. Compared with the control group, CVVH based on conventional treatment of severe sepsis could significantly reduce the incidence of MODS (10.8% vs. 29.7%, χ2 = 4.423, P = 0.038) and mortality (5.4% vs. 13.5%, χ2 = 4.674, P = 0.032), and remarkably shortened the duration of mechanical ventilation (days: 3.1±0.6 vs. 5.3±1.7, t = 2.103, P = 0.045), and the length of intensive care unit (ICU) stay (days: 8.5±1.7 vs. 13.2±2.4, t = 2.245, P = 0.042). Conclusion Early CBP can decrease the level of pro-inflammatory cytokines, prevent MODS, and remarkably improve the prognosis of patients with severe sepsis.
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The transient receptor potential( TRP) subfamilies be-long to the non-selective cation channels located at cell mem-branes. Calcium across the plasma membrane into the cell via most TRP channels may result in localized Ca2+ signals that con-tribute to cell proliferation, migration and metastasis. In recent years, many studies have focused on the role of TRP in cancer. This review intends to gather the latest progress concerning TRP channels on proliferation and migration of cancer.
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Objective To investigate the inhibitory effect of melatonin on the proliferation activity of murine foregastic carcinomac ( MFC) cells via melatonin membrane receptors MT 2 and its relationship with the signaling pathways of mitogen-activated protein kinases ( MAPKs), phosphatidylinositol 3-kinase ( PI3K)-Akt.Methods Using siRNA technology to silence MT2 expression, we examined the ability of melatonin to inhibit the proliferation activity of MFC cells and its influence on the phosphorylation of ERK 1/2 and Akt.Results We found two interesting effects of SiRNA-mediated silencing of MT2 expression.Firstly, it significantly antagonized the inhibitory effect of melatonin on the proliferation activity of MFC cells .Secondly , it partially blocked the inhibitory effect of melatonin on the phosphorylation of ERK 1/2 and Akt.Conclusion Our results suggest that melatonin can inhibit the phosphorylation of ERK 1/2 and Akt via MT2 receptors , thereby inhibiting the proliferation of gastric cancer cells .
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Objective To investigate the influence of pinealectomy(Px)and melatonin (MLT) supplementation on CD4~+CD25~+Treg cells development and Foxp3 expression in rat thymus. Methods One hundred and twenty clean-grade male SD rats were divided into five groups: normal control group, sham pinealectomized group, pinealectomized group, Px +7.5 mg/(kg·d) MLT group, Px +15 mg/(kg·d) MLT group, and the thymus were taken out at the 4th week and the 8th week;Flow cytometric analysis was used to analyse the number of double positive cells in the thymus and peripheral blood;Semiquantitative RT-PCR and immunohistochemistry were applied to analyse Foxp3 expression of rat thymus. Results There was no difference of the number of CD4~+CD25~+ Treg cells in rat thymus between Px and normal/sham group, and the number increased dependently on time and dose after MLT supplementation. In rat peripheral blood the double positive cells significantly increased in models of Px at the 4th week, and then backed to normal level after MLT supplementation. The results showed no significant changes in all groups at the 8th weeek;At the 4th weeks, Foxp3 expression increased in the thymus of Px rats compared to nomal/sham group, which returned to normal level after MLT supplementation. On the other hand, Foxp3 expression showed no significant difference in all groups at the 8th weeek.Conclusion Px made no difference between the development of CD4~+CD25~+Treg cells in rat thymus, but resulted in significant increase of thymic output and Foxp3 expression. All the effects disappeared at the 8th week. MLT supplementation could reverse the abnormity.
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Objective To explore the effectiveness of early enteral nutrition (EN) support and growth hormone (GH) treatment in critically ill patients.Methods Seventy critically ill patients were randomly divided into early EN support group and early EN support plus GH treatment group.The nutrition intakes were isonitrogenic and isocalorie in these two groups.Body weight,blood biochemistry,nutritional statues,and lactulose/mannitol levels were measured or analyzed before and after nutrition support.Immunologic functions were analyzed after ten days.Nitrogen balance was measured daily.Results The changes of body weight,albumin level,and transferrin level were more obvious in the EN + GH group than those in the EN group without significant difference (P ＞0.05).The changes of prealbumin and fibronectin in the EN + GH group were significantly higher than those in the EN group (P ＜ 0.05).The level of IgA in the EN + GH group was significantly lower than that in the EN group,while the levels of CD4 and NK in the EN + GH group was significandy higher than those in the EN group (P ＜0.05).The gut barrier function in the EN + GH group was superior to that in the EN group during nutrition support (P ＜0.05).Nitrogen balance was positive in the EN + GH group and negative in the EN group (P ＜ 0.05).Conclusions Early EN can improve the nutritional status and reduce complications in critically ill patients.GH treatment may strengthen the immune function and remarkably decrease the disability and mortality in critically ill patients.
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BACKGROUND: Parkinson disease is a common degenerative disorder of nervous system. Transplantation of embryonic stem cell can alleviate the symptoms of Parkinson disease, but restricted technically and ethically. Compared with embryonic stem cell, the various characteristics of bone marrow derived-multipotent adult progenitor cells (MAPCs) enable them to become one the ideal sources of cells for cell transplantation.OBJECTIVE: To explore the hypothesis that MAPCs were able to enter the brain and reduce the neurological functional deficits in rats by injecting intravenously.DESTGN: A randomized controlled experiment.ETTING: Department of Neurology, Wuhan First Hospital.MATERIALS: The experiments were performed in the laboratory of Department of Neurology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from October 2003 to March 2005. Eighty healthy Sprague-Dawley (SD) rats of 180-200 g were provided by the experimental animal center of Tongji Medical College,Huazhong University of Science and Technology.METHODS: The rats were made into models of Parkinson disease, the bone marrow-derived MAPCs, which were in vitro purified, proliferated and treated with 5-bromo-2-deoxyuridine (BrdU), were injected via caudal vein. After three months,the immunohistochemical technique, reverse transcription-polymerase chain reaction (RT-PCR), electron microscopy and behavioral tests were used to identify the MAPCs or neuron-like cells derived from MAPCs in brain and their functions.MAIN OUTCOME MEASURES: ① Results of behavioral observation; ② Results of immunihistochemical staining.RESULTS: After implantation, MAPCs could survive and differentiate into neuron-like cells in substantia nigra and striatum. MAPCs-derived dopaminergic neurons caused gradual and sustained behavioral restoration of 6-hydroxydopamine (6-OHDA)-mediated motor asymmetry. The levels of dopamine beta-hydroxylase (DBH), nerve growth factor (NGF) or dopamine transporter (DAT) mRNA were up-regulated significantly. It was observed under electron microscope that immature synapse implicated MAPCs- derived neuron should play an important role in the reconstruction of neural circuitry.CONCLUSION: Transplanted bone marrow derived-MAPCs can spontaneously differentiate into dopaminergic neurons,and act the corresponding nerve function.
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20 between the two groups.Gastric juice pH of two groups were higher than normal reference,and the inhibition of gastric acid in the treatment group was stronger than that of the control group(P
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In order to explore whether the member of Bcl-2 gene family, for example, Bcl-2 and Bax, are induced after cerebral ischemia, and whether expression of genes can be modulated by calcium-antagonist, the rat cerebral ischemic models were made by occluding left middle cerebral artery. The expression of Bcl-2 and Bax mRNA was measured by RT-PCR method. After middle cerebral artery occlusion (MCAO), the expression of both Bcl-2 and Bax mRNA were induced. Level of Bcl-2 mRNA increased steadily and level of Bax mRNA increased gradually at first, reached a peak after 24 h, then decreased slowly. After administration of nimodipine, Bcl-2 mRNA was up-regulated in the hippocampus 6 and 24 h after ischemia, while Bax mRNA was down-regulated 6 and 24 h after ischemia. Focal cerebral ischemia can induce proto-oncogenes to express, which was associated with apoptosis. Calcium-antagonist can up-regulate Bcl-2 mRNA and down-regulate Bax mRNA. The increased ratio of Bcl-2 and Bax mRNA may contribute to the anti-apoptic effect of nimodipine. The study indicates that pharmacological modulation of Bcl-2 family member expression could become a new strategy to manage neuronal damage.
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Animals , Rats , Apoptosis , Brain Ischemia , Metabolism , Calcium Channel Blockers , Pharmacology , Nimodipine , Pharmacology , Proto-Oncogene Proteins c-bcl-2 , Genetics , RNA, Messenger , Genetics , Rats, Wistar , bcl-2-Associated X Protein , GeneticsABSTRACT
Objective To investigate the relationship between ovary excision and serum levels of TNF ?, TGF ? 1. Methods Serum levels of TNF ? and TGF ? 1 in ovariectomized rats were measured by ELISA. Results The serum levels of TNF ? were increased〔(53 88?16 35)ng/L〕, but the TGF ? 1 were decreased 〔(6 78?0 75)?g/L〕 in ovariectomized rats when E 2 decreased compared with those of the Sham group( P
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Objective To explore Bcl-2 and Bax gene expression in hippocampus region after cerebral ischemia in rats and the modulation of expression by Nimodipine.Methods The cerebral ischemic model of rat was made by occluding left middle cerebral artery according to Nagasawy and Zea Longa improvement method. The rats in one group were pre-treated with Nimodipine. The expression of Bcl-2 and Bax mRNA were measured by RT-PCR method.Results Both Bcl-2 and Bax mRNA were induced in the hippocampus regions after middle cerebral artery occlusion. The Bcl-2 mRNA level was continuously high. However,the level of Bax mRNA increased gradually at first,reached a peak at 24 h,then decreased slowly.For the rats pretreated with Nimodipine Bcl-2 mRNA was up-regulated and Bax mRNA was down-regulated in the hippocampus at 6 and 24 h after ischemia.Conclusion Calcium antagonist can regulate Bcl-2 and Bax genes expression in the hippocampus region after cerebral ischemia.This study indicates that pharmacological modulation of Bcl-2 family member expression may become a new strategy to interfere with neuronal damage.
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Objective To investigate the effect of pinealectomy and melatonin on the dead signal path of thymocyte in rat. Methods SD rats were divided into 5 groups:normal control,sham-operated control,pinealectomy,pinealectomy+melatonin injection 7.5 mg/(kg\5d);and pinealectomy+melatonin injection 15 mg/(kg\5d).The animals were sacrificed at 4 or 8 weeks after operation.Fas/FasL\,caspase-8\,caspase-12 positive cells in thymus were stained with immunocytochemical ABC method,measured by compute image analysis.The TNF-? expression in thymocyte which was influenced by melatonin was tested by RT-PCR.(Results The) area of Fas positive cells in cortex was increased significantly at 4 weeks after Px,furthermore,this trend continued to enlarge 8 weeks after Px.The result of FasL staining was similar to the Fas.The area of caspase-8 positive thymic T cells increased significantly in both cortex and medulla 8 weeks after Px,but the difference showed no significance on caspase-12.Melatonin administration attenuated the effect caused by Px.The TNF-? expression in cultured rat thymocyte was decrease by melatonin administration.Conclusion Pineal gland can regulate the apoptosis of rat thymocyte by inflence the dead signal path.Rejuvenation of degenerative thymus could be observed by melatonin administration.
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Objective To study the effect of pinealctomy and melatonin on the cell cycle distribution during T cell development in thymus. Methods SD rats were divided into 5 groups:normal controls,sham-operated controls,pinealectomy,pinealectomy+melatonin injection 7.5 mg/kg; and pinealectomy+melatonin injection 15 mg/kg.The animals were sacrificed at 4 or 8 weeks after operation.cycilnA +and cyclinE +T cells in thymus were dyed with immunocytochemical ABC methods, measured by computer image analysis.Cell cycle analysis was performed by flow cytometry.The expression of cyclin-dependent kinase inhibitor 1? was tested by RT-PCR method. Results The effect of pinealectomy on the expression of cyclinE was stronger than that of cycilnA. Pinealectomy promotes the synthesis of cyclinE in thymus.The percentage of G-0/G-1 phase cells was decreased and G-2/M phase cells was increased.These would be convalescente by supplement with melatonin,but the reaction to melatonin was differencet in thymus cortex and in medulla.Melatonin enhanced the expression of cyclin-dependent kinase inhibitor 1? in thymus.Conclusion Pinealectomy influences notably the T cells development in thymus.Rejuvenation of degenerative thymus could be observed by melatonin administration.