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Objective:To investigate the value of a cuproptosis-related differential long non-coding RNA (lncRNA) scoring formula related to the prognosis of clear cell renal cell carcinoma (ccRCC) patients in the clinical diagnosis, prognosis prediction and treatment options based on bioinformatics.Methods:Gene matrix and clinical data of ccRCC patients were obtained from the Cancer Genome Atlas (TCGA) database (update to 29 March, 2022). The expression data of 539 ccRCC tissues and 72 paracancerous normal tissues were collected from gene matrix; the data of 530 ccRCC were collected from clinical data. Pearson correlation analysis, Wilcoxon signed rank test and univariate Cox proportional risk model were used to analyze the screened cuproptosis-related differential lncRNA related to the prognosis. R software was used to randomly divide 530 ccRCC patients with survival data into training set (266 cases) and validation set (264 cases) according to approximate 1∶1 ratio. LASSO regression analysis was used to construct a cuproptosis-related differential lncRNA scoring formula and cross-validation was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the specificity and sensitivity of cuproptosis-related differential lncRNA scoring formula, and the area of the curve (AUC) was calculated. According to the median risk value, all patients were divided into the low-risk group and high-risk group; Kaplan-Meier method was used to analyze the difference in the overall survival (OS) of patients in the low-risk group and high-risk group. T test was used to detect the differences in the risk value of patients with different clinicopathological characteristics. R package rms was used to construct the nomogram for predicting 1-year, 3-year, 5-year OS rates of ccRCC patients, R package pRRophetic was used to predict the half-inhibitory concentration ( IC50) of common targeted drugs such as sorafenib and sunitinib in clinical treatment of ccRCC patients, and IC50 value of patients in low-risk group and high-risk group was compared by using Wilcoxon signed rank test. Tissue samples of 20 ccRCC patients who underwent radical nephrectomy and were diagnosed with pathology and the matched paracancerous normal tissues were collected from the First Hospital of Shanxi Medical University between June 2021 and December 2021. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of key lncRNA in ccRCC tissues. Results:Based on the expression matrix of 10 cuproptosis genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, CDKN2A) of ccRCC patients in TCGA database, 153 cuproptosis-related differential lncRNA related to the prognosis were identified. According to LASSO regression analysis, a scoring formula of 4 cuproptosis-related differential lncRNA related to the prognosis was obtained, risk value was calculated as 0.020×AC015912.3+0.011×AC026401.3+0.063×AC103706.1+(-0.076)×EPB41L4A-DT. All patients were divided into high-risk group (≥0.76) and low-risk group (<0.76) based on the median value (0.76). ROC curve analysis showed that the scoring formula had good prediction accuracy in 1-year, 3-year, 5-year OS rates. In training set, validation set, the total cohort, the OS of patients in the high-risk group was worse than that in the low-risk group (all P < 0.001). The age, pathological degree, tumor staging, risk value calculated by cuproptosis-related differential lncRNA were independent influencing factors of OS (all P < 0.001). There were statistically significant differences in the risk value calculated by cuproptosis-related differential lncRNA scoring formula among patients with different pathological degree, tumor staging, T staging, N staging, M staging (all P < 0.01), while there were no statistically significant differences among patients with different gender and age (all P > 0.05). The established nomogram had good prediction accuracy in the 1-year, 3-year, 5-year OS rates. Sunitinib and sirolimus showed higher sensitivity in the high-risk group; axitinib, sorafenib and pazopanib showed higher sensitivity in the low-risk group. qRT-PCR results showed that relative expression level of AC015912.3 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.04 vs. 0.68±0.24, t = 6.37, P < 0.01); the relative expression level of AC026401.3 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.05 vs. 0.64±0.22, t = 7.29, P < 0.01); the relative expression level of AC103706.1 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.04 vs. 0.64±0.21, t = 7.49, P < 0.01); the relative expression level of EPB41L4A-DT in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.06 vs. 0.73±0.10, t = 10.68, P < 0.01). Conclusions:Cuproptosis-related differential lncRNA scoring formula based on TCGA database can be used as a new marker for clinical diagnosis and prognosis prediction of ccRCC patients, which can help guide the clinical drug treatment of patients and facilitate accurate diagnosis and treatment.
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Objective:To screen key genes of renal clear cell carcinoma based on bioinformatics methods, identify possible microRNA (miRNA)-mRNA action axis, and explore the expression of related genes in clear cell renal cell carcinoma tissues and cells.Methods:Gene expression profiles of GSE40435 and GSE71302 datasets were obtained from the Gene Expression Omnibus (GEO) database. TCGA-KIRC datasets were obtained from The Cancer Genome Atlas (TCGA) database. R software was used to identify the differentially expressed mRNA and miRNA, and the functional enrichment analysis was performed. STRING database and Cytoscape software were used to perform the protein interaction analysis. The prognosis-related differentially expressed miRNA was evaluated by the Oncomir database. The potential targeted genes regulated by miRNA were determined by using TargetScan and miRDB targeted gene prediction tools. The tissue samples and clinicopathological features of 34 patients with clear cell renal cell carcinoma in the First Hospital of Shanxi Medical University from June to December 2021 were collected, and normal renal cell line 293T and clear cell renal cell carcinoma cell line 786O were selected. The real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), was used to detect the relative expression of genes; Western blotting and immunohistochemical staining were used to detect the expression levels of the targeted proteins. The dual luciferase reporter gene assay was carried out to verify the targeting relationship between genes.Results:A total of 1 351 differentially expressed mRNA and 50 differentially expressed miRNA were screened and identified. The result of functional enrichment analysis suggested that the fatty acid metabolism pathway and xenobiotic metabolism pathway were suppressed in clear cell renal cell carcinoma, while the apoptosis and immune response pathways were activated. Protein interaction analysis suggested that the signal transduction and protein ubiquitination pathways might play a key role in clear cell renal cell carcinoma. The screening results showed that miRNA-224-5p (miR-224-5p) was most closely associated with clear cell renal cell carcinoma progression and was highly expressed in tumor tissues, and its prognosis-related target gene was NEDD4L. The relative expression of NEDD4L mRNA in clear cell renal cell carcinoma tissues and paraneoplastic tissues were 0.138±0.103 and 1.000±0.026 ( t = 46.23, P < 0.05), and the relative expression of miR-224-5p was 1.000±0.043 and 0.129±0.108 ( t = 45.28, P < 0.05). The differences of NEDD4L mRNA and miR-224-5p expressions in different grades and stages of clear cell renal cell carcinoma tissues were statistically significant (all P < 0.05). The expression of NEDD4L protein was decreased in clear cell renal cell carcinoma. The relative expression of NEDD4L gene in 293T and 786O cells were 1.000±0.125 and 0.210±0.044 ( t = 17.52, P < 0.05); the relative expressions of miR-224-5p gene were 0.209±0.049 and 1.000±0.234 ( t = 10.61, P < 0.05). The relative expressions of NEDD4L mRNA in miRNA mimic group and negative control group were 0.236±0.062 and 1.000±0.024, and the difference was statistically significant ( t = 43.56, P < 0.05). NEDD4L protein expression was reduced in the miRNA mimic group. Dual luciferase reporter gene assay suggested that NEDD4L was a direct target gene of miR-224-5p. Conclusions:In clear cell renal cell carcinoma, miR-224-5p targets and regulates NEDD4L expression, and this mechanism may be related to carcinogenesis and progression of clear cell renal cell carcinoma.
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Epstein-Barr virus (EBV) is generally susceptible in human beings and multi-organ systems can be involved in EBV infection, such as blood, respiratory, urinary, digestive and nervous systems. EBV infection also plays an important role in the pathogenesis of related tumors, autoimmune diseases and other diseases, posing a great threat to human health. As a DNA virus, EBV can be sensed by DNA recognition receptors to trigger a series of downstream immune responses. A DNA-sensing pathway consists of DNA sensors, adaptor molecules and downstream effector signals. Double-stranded DNA sensors mainly include absent in melanoma 2-like receptors (ALRs) and cyclic GMP-AMP synthase (cGAS). Adaptors were mainly stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Downstream immune responses mainly involve typeⅠIFN, inflammasomes and proinflammatory cytokines. As a double-stranded DNA virus of the Herpesviridae family, EBV triggers complex innate and adaptive immune responses in the host, especially the sensing pathways mediated by a variety of DNA recognition receptors, which play a key role in host immune defense and pathogen immune evasion. This review made the DNA sensor as the clue to comprehensively summarize the progress in the activation, regulatory mechanism and clinical relevance of DNA-sensing pathways in EBV infection in recent years, aiming to achieve a better understanding of the host innate immune responses during EBV infection and provide an immunological basis for the prevention and treatment of EBV infection-related diseases.
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Glioma is the most common primary intracranial tumor. At present, the conventional treatment methods have limited effect and cannot significantly prolong the survival time of patients. Chemokine CCL2 is the most important member of the CC chemokine family, which can regulate glioma angiogenesis, immunosuppression, progression and invasion, and resistance to apoptosis. This article reviews the potential mechanism of CCL2 promoting the malignant progression of glioma, in order to provide new ideas and methods for the targeted therapy of glioma.
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Metastatic castration-resistant prostate cancer (mCRPC) is the inevitable form of most prostate cancers after endocrine therapy, and conventional drugs are not effective at this time.In this case, an elderly mCRPC patient with cardiopulmonary diseases admitted to the First Hospital of Shanxi Medical University in August 2020 was selected. After the failure of traditional endocrine therapy, enzalumide+ ADT regimen was adopted, and the patient's blood PSA was significantly reduced without cardiopulmonary adverse events.
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OBJECTIVES@#To explore the effect of etomidate on the neuronal activity of ventral thalamic reuniens nucleus and the underlying mechanisms.@*METHODS@#Whole-cell patch clamp method was used to explore the effect of etomidate on the activity of ventral thalamic reuniens neurons in the acute brain slices obtained from 4-5 weeks old C57BL/6J mice. The electrophysiological characteristics of ventral thalamic reuniens neurons were recorded in the current clamp mode, and then the effects of etomidate (0.5, 2.0, 8.0 μmol/L etomidate groups) and intralipid (intralipid group) on the discharge frequency and membrane potential of ventral thalamic reuniens neurons were recorded. During the experiment, the ventral thalamic reuniens neuron firing rates (RNFRs) were recorded as F@*RESULTS@#In the intralipid group, there was no significant difference among the F@*CONCLUSIONS@#Etomidate can inhibit the activity of ventral thalamic reuniens neurons in concentration-dependent manner, and which is reversible. Etomidate with sub-anesthetic concentration inhibits the activity of ventral thalamic reuniens neurons via targeting the GABA
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Animals , Mice , Etomidate/pharmacology , Mice, Inbred C57BL , Neurons , Patch-Clamp Techniques , Receptors, GABA-AABSTRACT
Objective@#To evaluate the effect of different hemoglobin (Hb) concentrations on the lung injury in a rabbit model of hemorrhagic shock and resuscitation (HS-R).@*Methods@#Fifty healthy male New Zealand rabbits, aged 2 months, weighing 1.9-2.4 kg, were divided into 5 groups (n=10 each) using a random number table method: control group (group C), HS-R group (group H), and three HS-R plus infusion of concentrated red blood cell groups group R1 (60 g/L≤Hb<80 g/L), group R2 (80 g/L≤Hb<100 g/L) and group R3 (100 g/L≤Hb<120 g/L). The animals were sacrificed at 3 h after resuscitation, lung tissues were obtained for examination of the pathological changes with a light microscope, and lung tissues were obtained again for determination of wet to dry weight ratio (W/D ratio), neutrophil myeloperoxidase (MPO), NO level and cell apoptosis (by TUNEL).@*Results@#Compared with group C, the levels of MAP and NO, W/D ratio and apoptosis index were significantly increased in the other groups (P<0.05). Compared with group H, the levels of MAP and NO, W/D ratio and apoptosis index were significantly decreased in R2 and R3 groups (P<0.05). Compared with group R2, the apoptosis index was significantly increased at T5(P<0.05), and no significant change was found in the other parameters in group R3 (P>0.05).@*Conclusion@#Maintaining Hb 80-100 g/L after HS-R reduces acute lung injury in rabbits.
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Objective@#To evaluate the accuracy of aortic valve velocity time integral (VTI) in assessing fluid responsiveness during general anesthesia in elderly patients.@*Methods@#Forty-four elderly patients of both sexes, aged 65-80 yr, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, with New York Heart Association classⅠ or Ⅱ, undergoing elective surgery with general anesthesia in our hospital from February 2018 to August 2018, were enrolled in this study.All the patients underwent tracheal intubation after general anesthesia induction, and then volume expansion was carried out (6% hydroxyethyl starch 250 ml was intravenously infused for 30 min). The heart rate (HR), mean arterial pressure (MAP), VTI and stroke volume (SV) were recorded before and after volume expansion, and ΔHR, ΔMAP, ΔVTI and ΔSV were calculated.Patients were divided into 2 groups according to ΔSV: response group (R group, ΔSV≥15%) and non-response group (NR group, ΔSV<15%). The receiver operating characteristic curve (with the area under the standard ΔSV curve was 1) was used to analyze the ΔHR, ΔMAP and ΔVTI, and the Youden index at its best was calculated.The Person test was used to analyze the correlation between ΔVTI and ΔSV.@*Results@#There were 25 cases in R group and 19 cases in NR group.Compared with group NR, ΔHR was significantly decreased, and ΔVTI and ΔSV were increased in group R (P<0.05). The area under the ROC curve of ΔHR, ΔMAP and ΔVTI in assessing fluid responsiveness was 0.509 (95% confidence interval 0.314-0.689, P=0.415), 0.558 (95% confidence interval 0.379-0.737, P=0.515) and 0.905 (95% confidence interval 0.812-0.999, P<0.01), respectively. When Youden index was at its best, ΔVTI was 15.28%, with the sensitivity 88.0% and specificity 94.7%.There was a positive correlation between ΔSV and ΔVTI (r=0.936, P<0.05).@*Conclusion@#ΔVTI can accurately assess the fluid responsiveness during general anesthesia in elderly patients.
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Objective To evaluate the effect of different hemoglobin(Hb)concentrations on the lung injury in a rabbit model of hemorrhagic shock and resuscitation(HS-R).Methods Fifty healthy male New Zealand rabbits,aged 2 months,weighing 1.9-2.4 kg,were divided into 5 groups(n＝10 each)u-sing a random number table method: control group(group C),HS-R group(group H),and three HS-R plus infusion of concentrated red blood cell groups group R1(60 g/L≤Hb＜80 g/L),group R2(80 g/L≤Hb＜100 g/L)and group R3(100 g/L≤Hb＜120 g/L).The animals were sacrificed at 3 h after resuscita-tion,lung tissues were obtained for examination of the pathological changes with a light microscope,and lung tissues were obtained again for determination of wet to dry weight ratio(W/D ratio),neutrophil my-eloperoxidase(MPO),NO level and cell apoptosis(by TUNEL).Results Compared with group C,the levels of MAP and NO,W/D ratio and apoptosis index were significantly increased in the other groups(P＜0.05).Compared with group H,the levels of MAP and NO,W/D ratio and apoptosis index were signifi-cantly decreased in R2 and R3 groups(P＜0.05).Compared with group R2,the apoptosis index was signif-icantly increased at T5(P＜0.05),and no significant change was found in the other parameters in group R3(P>0.05).Conclusion Maintaining Hb 80-100 g/L after HS-R reduces acute lung injury in rabbits.
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Objective To evaluate the accuracy of aortic valve velocity time integral(VTI)in as-sessing fluid responsiveness during general anesthesia in elderly patients.Methods Forty-four elderly pa-tients of both sexes,aged 65-80 yr,of American Society of Anesthesiologists physical status Ⅰ-Ⅲ,with New York Heart Association classⅠorⅡ,undergoing elective surgery with general anesthesia in our hospi-tal from February 2018 to August 2018,were enrolled in this study.All the patients underwent tracheal in-tubation after general anesthesia induction,and then volume expansion was carried out(6％hydroxyethyl starch 250 ml was intravenously infused for 30 min).The heart rate(HR),mean arterial pressure(MAP),VTI and stroke volume(SV)were recorded before and after volume expansion,and ΔHR,ΔMAP,ΔVTI and ΔSV were calculated.Patients were divided into 2 groups according to ΔSV: response group(R group,ΔSV≥15％)and non-response group(NR group,ΔSV＜15％).The receiver operating characteristic curve(with the area under the standard ΔSV curve was 1)was used to analyze the ΔHR,ΔMAP and ΔVTI,and the Youden index at its best was calculated.The Person test was used to analyze the correlation between ΔVTI and ΔSV.Results There were 25 cases in R group and 19 cases in NR group.Compared with group NR,ΔHR was significantly decreased,and ΔVTI and ΔSV were increased in group R(P＜0.05).The area under the ROC curve of ΔHR,ΔMAP and ΔVTI in assessing fluid responsiveness was 0.509(95％confidence interval 0.314-0.689,P＝0.415),0.558(95％confidence interval 0.379-0.737,P＝0.515)and 0.905(95％confidence interval 0.812-0.999,P＜0.01),respectively.When Youden index was at its best,ΔVTI was 15.28％,with the sensitivity 88.0％and specificity 94.7％.There was a positive correlation between ΔSV and ΔVTI(r＝0.936,P＜0.05).Conclusion ΔVTI can accurately assess the fluid responsiveness during general anesthesia in elderly patients.
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To investigate the role of p38MAPK signal pathway in spinal cord and dorsal root ganglion (DRG) in rats with phantom limb pain and the effects of specific inhibitors. Methods: Healthy adult male SD rats (n=48) were cut off one side of the sciatic under anesthesia to establish a model of phantom limb pain. In addition, the healthy rats were taken as a sham group (group S, n=24). The animals were scored by observing the action of chewing (0=no chewing, 13=the worst chewing) after the operation and were sacrificed on the following day after the operation. The successful model of phantom limb pain were randomly divided into 2 groups: a phantom limb pain group (group P, n=24) and a phantom limb pain plus inhibitor group (group P+I, n=24). SB203580 was given to the rat at 0.8 mg/kg on every Monday until the rats were sacrificed, the rest of the rats received an equal amount of saline. Eight rats from each group were randomly taken for the determination of levels of P-p38MAPK in spinal cord and DRG before administration and on the 4th, 6th, 8th weekend following the administration, respectively. Results: In the sham group, no animal developed chewing. Meanwhile, rats in successful model of phantom limb pain group began chewing from the 2nd day after operation with scores at eight to eleven. The chewing scores in the P+I group were reduced after the treatment. Compared with group S, P-p38MAPK levels were elevated in groups of P and P+I (P<0.05 or P<0.01). Compared with group P, P-p38MAPK level was decreased in the group P+I (P<0.05 or P<0.01). Conclusion: P38MAPK signal pathway involves in the development of phantom limb pain.
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Animals , Male , Rats , Disease Models, Animal , Enzyme Inhibitors , Pharmacology , Ganglia, Spinal , Imidazoles , Pharmacology , Mastication , Physiology , Phantom Limb , Pyridines , Pharmacology , Random Allocation , Rats, Sprague-Dawley , Sciatic Nerve , Wounds and Injuries , Self Mutilation , Signal Transduction , Spinal Cord , p38 Mitogen-Activated Protein Kinases , MetabolismABSTRACT
Objective To study the regional homogeneity (ReHo) of default-mode network (DMN) in patients with minimal hepatic encephalopathy (MHE) with resting state fMRI.Methods Eighteen MHE patients and eighteen healthy controls (HC) underwent standard resting state fMRI scan.The resting state fMRI data were analyzed with the ReHo method to observe the changes of DMN in the patients in contrast to the controls.Results Compared to healthy controls,MHE patients showed lower ReHo in bilateral MPFC/anterior cingulate cortex(V=13.257 cm3;MNI coordinates=3,24,66;t=-3.493 7),bilateral precuneus/posterior cingulate cortex(V=4.752 cm3;MNI coordinates=9,-54,45;t=-2.634 1),while higher ReHe in right medial prefrontal cortex(V=5.049 cm3;MNI coordinates=21,63,6;t=4.017 5).Conclusion In MHE patients,there is abnormal neuron activation in the widespread DMN regions under resting state, which indicated abnormal spontaneous activity consistency within DMN and endogenous brain function injury in MHE patients.ReHo can be used to observe DMN changes in MHE patients.
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Objective To explore the effects of miRNA-204 targeted LC3B expression on Ang Ⅱ induced cardiomyocytes hypertrophy.Methods The primary neonatal rat cardiomyocytes served as the research objects and divided into the control group,AngⅡ group,combination-treated group 1 (cardiomyocytes were given Ang Ⅱ stimulation,meanwhile infected by negative control lentivirus vector),combination-treated group 2 (cardiomyocytes were given Ang Ⅱ stimulation,meanwhile infected by lentivirus carrying miRNA-204 overexpression vector) according to different treatments.About 48 h to 72 h after intervention treatment,the cardiomyocyte hypertrophy change was detected by confocal microscopy,the expression of miRNA-204 was analyzed by real time PCR,the protein expression of LC3B was measured by Western blot and targeted gene of miRNA-204 was demonstrated by dual-luciferase reporter assay system.Results Compared with the control group,the cardiomyocyte relative surface area in the Ang Ⅱ group was significantly enlarged,the protein expression of LC3B was significantly increased,the expression of miRNA-204 was upregulated,the differences were statistically significant (P＜0.05).Whereas comparing the combination-treated group 1 with combination-treated group 2,the protein expression of LC3B in the latter was down-regulated and the cell area was reduced (P＜0.05).The further luciferase activity report gene experiment results suggested that miRNA-204 was able to bind to LC3B 3'-UTR and decreased the luciferase activities (P＜0.05),but not to bind its mutated fragment for inactivating luciferase activity(P＞0.05).Conclusion miRNA-204 is able to inhibit Ang Ⅱ induced cardiomyocytes hypertrophy,its action is realized by targeting the expression of LC3B.
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Objective To investigate the effects of erythropoietin (EPO) on myocardial apoptosis and protein kinase B (AKT) expression in rats of chronic heart failure (CHF). Methods Thirty male adult SD rats were randomly divided into two groups, sham-operated (Sham) group (n=6) and model (Model) group (n=24). The abdominal aortic coarctation was used to build CHF model. Sixteen survived rats after operation were randomly divided into two groups including EPO group and con-trol (Control) group. EPO group was received 3 000 U/kg EPO intraperitoneal injection 3 times/week for 4 weeks, and Sham group and Control group were received same volume of normal saline. The echocardiography was used to evaluate cardiac function after 4 weeks, 8 weeks and 12 weeks of treatment. After 12 weeks, all rats were sacrificed after 24 h fasting. The cell morphology and myocardial apoptosis were observed, and apoptosis index (AI) was calculated. Myocardial P-AKT/AKT pro-tein expression was detected by Western blot assay. Results Echocardiography showed that ventricular hypertrophy was found in model group after four weeks, heart failure 8 weeks. Compared with Control group, left ventricular ejection fraction (LVEF) was significantly higher after EPO intervention for 4 weeks (P < 0.05), systolic interventricular septum thickness (IVSs), end-systolic left ventricular posterior wall thickness (LVPWs), diastolic interventricular septum thickness (IVSd), af-ter left ventricular end-diastolic wall thickness (LVPWd) were significantly lower (P<0.05). The value of AI was significant-ly lower in EPO group than that of Control group (23.87%±1.45%vs 35.58%±2.81%, P<0.01). The OD value of P-AKT/AKT was significantly decreased in Control group (0.35±0.06) than that of Sham group (0.81±0.17), the value was significant-ly increased in EPO group (1.61±0.16) than that of Control group (P<0.01). Conclusion EPO can improve heart function, inhibit myocardial apoptosis,and promote pro-phosphorylation of AKT in rats with chronic heart failure.
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Objective To explore the effects of miR-34a and the alteration of AMPK/mTOR signal pathway on angiotensin (Ang)Ⅱ-stimulated cardiomyocytes hypertrophy. Methods Neonatal rat cardiomyocytes were cultrued in vitro and were divided into 3 groups:negative control for lentivirus carrying miR-34a group (NC), AngⅡplus lentivirus carrying negative control group (AngⅡ+NC) and AngⅡplus lentivirus carrying miR-34a group (AngⅡ+miR-34a). The relative cell area was detected by confocal microscopy. The expression of miR-34a and hypertrophy-related genes (ANP and β-MHC) were analyzed by real time PCR. The AMPK/mTOR signal pathway was measured by Western blot assay. Results Compared to NC group, the relative cell area was increased in AngⅡ+NC group (P<0.05). But compared with AngⅡ+NC group, the relative cell area was decreased in AngII+miR-34a group (P<0.05). Moreover, compared with NC group, the expression of miR-34a was decreased, and the expression of hyperthophy-related genes(ANP and β-MHC) was up-regulated in AngⅡ+NC group. However, the expression of miR-34a was decreased, and the expression of hyperthophy-related genes (ANP and β-MHC) was down-regulated (P<0.05). Finally, compared to NC group, the ratio of phosphop-AMPK/AMPK was significantly induced in AngII + NC group, but the ratio of phosphop-mTOR/mTOR was significantly decreased (P<0.05). However, compared to AngⅡ+NC group, the ratio of phosphop-AMPK/AMPK was significantly decreased in AngII + miR-34a group, but the ratio of phosphop-mTOR/mTOR was significantly increased (P<0.05). Conclusion miR-34a is able to inhibit myocardial hypertrophy of neonatal rat cardiomyocytes, and its mechanism is partly carried out by the alteration of the signal pathway of AMPK/mTOR.
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Objective To investigate the distribution of 3279 and 924 Foxp3 genotypes in Guangdong population and to explore the correlation between Foxp3 gene polymorphism and essential hypertention . Methods Two hundred and six essential hypertention patients and 291 healthycontrols from October 2013 to September 2014 in the third affiliated hospital of guangzhou medical university were enrolled in the study. The Foxp3 3279 and 924 genotypes was identified by PCR-SSP assay. The plasma lipid level and other risk factor were detemined in all subjects. The relationship between genotypes and pathogenesis of EH was analyzed. Results There were sigificant differences in frequecncies of allele and genotype distribution in Foxp3 3279 genotypes between the two groups. The frequecies of AC+CC and allele were significantly higher in the EH group than those in the control group (P<0.05). Result of logictics analysis showed that AC+CC genotype significantly increase the risk of EH (OR = 1.552,95%CI为1.021 ~ 2.357, P < 0.05), but the polymorphism of Foxp3 924 genotype frequecncy was not assosiated with EH. Conclusion The Foxp3 3279 gene polymorphisms is associated with EH . However, the Foxp3 924 gene polymorphisms is not associated with EH.
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Objective To evaluate the efficacy of dexmedetomidine mixed with ropivacaine for transversus abdominis plane (TAP) block combined with general anesthesia in the patients undergoing gynecological laparoscopy.Methods Ninety American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 20-50 yr, with body mass index of 18-24 kg/m2, scheduled for elective gynecological laparoscopic ovarian cyst resection under general anesthesia, were randomly divided into 3 groups (n =30 each) using a random number table: general anesthesia group (group G) , general anesthesia + ropivacaine for TAP block group (group G+R), and general anesthesia + dexanedetomidine mixed with ropivacaine for TAP block group (group G+DR).After the end of anesthesia induction, ultrasound-guided left-sided unilateral TAP block was performed in G+R and G+DR groups.In G+R and G+DR groups, 20 ml of 0.375％ ropivacaine and 20 ml of 0.375％ ropivacaine mixed with 1 μg/kg dexmedetomidine were injected, respectively.After induction of general anesthesia, the laryngeal mask airway (LMA) was inserted, and the patients were mechanically ventilated in the 3 groups.Anesthesia was maintenaned with iv infusion of remifentanil 0.2 μg · kg-1 · min-1 and propofol 4-8 mg · kg-1 · h-1.Narcotrend index was maintained at 37-46.Only group G received postoperative intravenous analgesia.The occurrence of TAP block-related adverse events was recorded.The emergence time, time for recovery of spontaneous breathing, time for removal of LMA, and Steward score at 5 min after removal of LMA were recorded.The occurrence of postoperative nausea and vomiting, and respiratory depression was recorded.Results Compared with G and G+R groups,the emergence time, time for recovery of spontaneous breathing, and time for removal of LMA were significantly shortened (P＜0.05 or 0.01) , and no significant change was found in Steward score in group G+DR (P＞0.05).There was no significant difference in the above parameters between group G and group G+R (P＞0.05).Compared with group G, the incidence of postoperative nausea and vomiting was significantly decreased in G+R and G+DR groups (P＜0.05).VAS score was maintained ≤ 3 after operation in the 3 groups.No TAP block-related adverse events were found in G+R and G+DR groups.Conclusion Dexmedetomidine mixed with ropivacaine provides faster recovery from anesthesia, and avoids postoperative hyperalgesia when used for TAP block combined with general anesthesia in the patients undergoing gynecological laparoscopy.
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OBJECTIVE@#To determine the effect of stellate ganglion block on reconstruction of the left ventricle in spontaneously hypertensive rats (SHRs).@*METHODS@#Thirty-two 10-week-old male SHRs were randomly assigned into 4 groups: a left stellate ganglion block group (group LS), a right stellate ganglion block group (group RS), a captopril group (group D) and a control group (group C). The arterial systolic blood pressure (SBP) was measured by ALC-NIBP measuring system. After 10 weeks, we observed the left ventricular mass index (LVMI), myocardial pathologic changes, and detected the endothelin (ET-1) and endothelial nitric oxide synthase (eNOS) level in the left ventricle by radioimmunoassay and the collagen protein level in the left ventricle by immunohistochemical method.@*RESULTS@#Compared with group LS and group C, the LVMI in group RS was lowered most notably (P<0.05) and pathological changes were improved obviously. The expression of eNOS in group RS was significantly increased and ET-1 significantly decreased (P<0.05) compared with that in group C and group LS. The expression of type I collagen fibers in group RS was significantly lower and type III collagen fibers significantly higher (P<0.05) when compared with that in group C and LS.@*CONCLUSION@#Right stellate ganglion block can not only decrease the arterial pressure but also reverse the reconstruction of the left ventricle.
Subject(s)
Animals , Male , Rats , Autonomic Nerve Block , Hypertension , Therapeutics , Rats, Inbred SHR , Stellate Ganglion , Ventricular Remodeling , PhysiologyABSTRACT
OBJECTIVE@#To investigate the relationship between apoptosis of myocardial cells in spontaneously hypertensive rats (SHRs) and the expressions of Bcl-2 and Bax protein, and the protective effect of stellate ganglion block on apoptosis of myocardial cells.@*METHODS@#A total of 32 ten-week-old male SHRs were assigned randomly into 4 groups: a left stellate ganglion block group (group LS), a right stellate ganglion block group (group RS), a captopril group (group D) and a control group (group C). The arterial systolic blood pressure was measured by ALC-NIBP system. After 10 weeks, all rats were anaesthetized by 3% pentobarbital sodium, cardiomyocyte apoptosis index of left ventricle was assessed by TUNEL, and the localization of myocardium Bcl-2, Bax was investigated by immunohistochemistry.@*RESULTS@#Compared with group LS and C, the apoptotic index decreased (P<0.05). SHR myocardial expression of Bcl-2 significantly increased (P<0.05), Bax expression significantly decreased (P<0.05) and Bcl-2/Bax was significantly higher (P<0. 05) in group RS.@*CONCLUSION@#Bcl-2 and Bax play an important role in the apoptosis of myocardial cells in SHRs. Right stellate ganglion block can reduce the apoptosis of myocardial cells and reverse the reconstruction of the left ventricle in SHRs via regulation of apoptosis-related gene proteins.
Subject(s)
Animals , Male , Rats , Apoptosis , Autonomic Nerve Block , Blood Pressure , Heart Ventricles , Myocardium , Myocytes, Cardiac , Cell Biology , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Rats, Inbred SHR , Stellate Ganglion , bcl-2-Associated X Protein , MetabolismABSTRACT
Objective To evaluate the effects of gender on the median effective target plasma concentration (EC50) of propofol inhibiting responses to laryngeal mask airway (LMA) insertion in patients.Methods Fiftyfive ASA physical status Ⅰ or Ⅱ patients,aged 20-60 yr,with body mass index 18-25 kg/m2,requiring LAM insertion,undergoing elective surgery,were divided into 2 groups according to the gender:male group (group M,n =27) and female group (group F,n =28).Propofol was given by target-controlled infusion.Anesthesia was induced with target-controlled infusion of propofol.The concentration of propofol was determined by using modified Dixon's up-and-down method.The initial target plasma concentration of propofol was 3.0 μg/ml (group M) or 2.7μg/ml (group F) and the ratio between the 2 successive concentrations was 1.1.Fentanyl 1 μg/kg was injected intravenously at about 10 min of propofol target-controlled infusion.LMA was inserted after the effect-site and plasma concentrations were balanced.The positive response to LMA insertion was defined as development of swallowing,coughing,biting LMA,body movement and laryngospasm during insertion.When the response to LMA insertion was positive,the concentration of propofol was increased in the next patient and when the response was negative,the concentration was decreased in the next patient.The EC50 and 95 ％ confidence interval of propofol inhibiting responses to LMA insertion were calculated.Results The EC50 (95 ％ confidence interval) of propofol was 3.11 (2.92-3.30) μg/ml in group F and 2.70 (2.55-2.85) μg/ml in group M (/ ＜ 0.05).Conclusion The EC50 of propofol inhibiting responses to LMA insertion is higher in female patients than in male patients.