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A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
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Humanos , Hormona Adrenocorticotrópica , Calor , Medicina Tradicional China , Adenosina TrifosfatoRESUMEN
This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.
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Humanos , Niño , Ratas , Animales , Puromicina Aminonucleósido , Metabolómica/métodos , Biomarcadores/orina , Cromatografía Líquida de Alta Presión/métodos , Acetofenonas , Glomerulonefritis , Fenilalanina , AminoácidosRESUMEN
This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and β-eudesmol as the main components. The quantitative results demonstrated good linearity(r>0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.
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Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de Masas , Reproducibilidad de los Resultados , Medicamentos Herbarios Chinos/químicaRESUMEN
This study aims to explore the relationship of DNA methylation with the contents of the index components as well as the growth and development of Pogostemon cablin. The demethylation reagent 5-azacytidine(5-azaC) was used to treat the tissue culture seedlings of patchouliol-type P. cablin. High performance liquid chromatography was employed to evaluate the changes of DNA methy-lation in P. cablin, and GC-MS to detect the contents of index components in P.cablin. The agronomic characters of P.cablin were measured using the common methods. The results showcased that DNA methylation of P.cablin was significantly reduced by 5-azaC in a concentration-dependent manner. Thirty days after treatment with 5-azaC at different concentrations, the content of patchouli alcohol changed slightly; compared with that in the control group, the content of pogostone in 50 μmol·L~(-1) and 100 μmol·L~(-1) 5-azaC groups was significantly up-regulated. The 100 μmol·L~(-1) 5-azaC group had the largest differences in contents of pogostone and patchouli alcohol compared with the control group, followed by the 50 μmol·L~(-1) 5-azaC group. Ninety days after disinhibition, the content of pogostone in the treatment group was significantly increased and the content of patchouli alcohol was significantly decreased. In addition, 5-azaC significantly inhibited the growth and development of P.cablin in a dose-dependent manner. These results indicate that DNA methylation regulates the biosynthesis of the index components in patchouliol-type P.cablin and proper demethylation can directly promote the synthesis of pogostone and indirectly affect the accumulation of patchouli alcohol.
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Azacitidina , Metilación de ADN , Cromatografía de Gases y Espectrometría de Masas , Aceites Volátiles , Pogostemon/genéticaRESUMEN
Objectives To investigate the efficiency and safety of ultrasound-guided microwave ablation (MWA) for hepatocellular carcinoma (HCC) adjacent to danger areas.Methods The 106 patients with HCC treated by ultrasound-guided MWA were retrospectively included in our study.There were 149 lesions in total,including 8 lesions adjacent to gallbladder,33 lesions adjacent to grade Ⅰ-Ⅱ bile duct,39 lesions adjacent to diaphragm,28 lesions adjacent to gastrointestinal tract and 41 lesions adjacent to hepatic capsule.The mean diameter of the tumors was (2.04 ±0.92)cm.Individualized treament strategies for different sites of the tumors were conducted.The early complete ablation rate of the tumors was assessed by enhanced computed tomography (CT) or magnetic resonance imaging (MRI) one month later and followed up regularly.Results The total inactivation rate was 89.9%.The early complete ablation rates of adjacent gallbladder,adjacent grade Ⅰ-Ⅱ bile duct,adjacent diaphragm,adjacent gastrointestinal tract and adjacent hepatic capsule were 100%,84.8%,89.7%,92.9%,90.2% respectively.The local progression rates were 0,15.2%,10.3%,7.1%,9.8%,respectively.The 1-,2-and 3-year survival rates were 91.6%,85.8% and 74.5%.Total cases were ablated 149 times.Serious complications accounted for 6.6%,including diaphragm injury,needle implantation,abdominal hemorrhage,severe infection,bile tumors.Conclusions Our study presented a novel individualized treament strategies using MWA in HCC patients.The individualized scheme effectively boosted the complete ablation rate of tumors and significantly improve the clinical outcome of HCC patients.
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BACKGROUND: Proximal humeral fracture is a common disease of fall injury in the elderly, because of bone nonunion after treatment with a variety of factors such as senile osteoporosis. Currently, the use of reverse total shoulder arthroplasty has achieved good clinical effect, but has certain limitations. OBJECTIVE: To compare and observe the clinical effects of reverse total shoulder arthroplasty and open reduction and internal plate fixation in the treatment of nonunion of proximal humeral fractures. METHODS: Totally 120 cases of nonunion of proximal humeral fractures were randomly divided into observation group and control group, with 60 cases in each group. The observation group received reverse total shoulder arthroplasty (replacement of artificial shoulder joint). The control group received open reduction and internal plate fixation. RESULTS AND CONCLUSION: (1) Follow-up results: At 3 years after surgery, the pain score was lower in the observation group than that in the control group (P < 0.05). Constant daily activities, range of activities, strength test score, Constant total score, satisfaction and hospitalization expenses were higher in the observation group than in the control group. Functions of flexion, laterotorsion and intorsion were better in the observation group than those in the control group (P < 0.05). (2) Adverse reactions: At 3 years after surgery, 26 and 22 cases had adverse reaction in the observation group and the control group respectively. (3) The results show that the clinical effect of the elders' nonunion of proximal humeral fracture treated with reverse total shoulder arthroplasty is quite good, and the pain degree and shoulder function are obviously improved. The curative effect of reverse total shoulder arthroplasty is better than that of open reduction and internal plate fixation.
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Objective To evaluate the effect of ambroxol on p38 mitogen-activated protein kinase pathway in mice with sepsis-induced lung injury.Methods Sixty male C57BL/6 mice were equally and randomly divided into 3 groups (n=20 each) using a random number table:sham operation group (group S),sepsis-induced lung injury group (group CLP),and sepsis-induced lung injury + ambroxol group (group AMB).Sespsis was produced by cecal ligation and puncture(CLP).Ambroxol 50 mg/kg preconditioning was injected intraperitoneally for 3 days in group AMB,while the equal volume of normal saline instead was given in S and VILI groups.The arterial blood gas was detected 24 h after CLP.Then the mice were sacrificed and broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of total protein,interleukin-1β (IL-1β),tumor necrosis factor-α (TNF-α),IL-6 and intercellular adhesion molecule-1 (ICAM-1).The lung tissues were taken for determination of wet to dry lung weight ratio (W/D ratio),expression of p-p38 MAPK,IL-1β mRNA,TNF-α mRNA,IL-6 mRNA and ICAM-1 mRNA,and for examination of the pathological changes which were scored.Results Compared with group S,partial pressure of oxygen in arterial blood(PaO2) was decreased (P<0.05),and W/D ratio,lung injury score,concentrations of total protein,IL-1β,TNF-α,IL-6 and ICAM-1 in BALF,and expression of p-p38 MAPK,IL-1β,TNF-α,IL-6 and ICAM-1 mRNA were significantly increased in CLP group (P<0.05).Compared with group CLP,PaO2 was increased (P<0.05),W/D ratio,lung injury score,concentrations of total protein,IL-1β,TNF-α,IL-6 and ICAM-1 in BALF,and expression of p-p38 MAPK,IL-1β,TNF-α,IL-6 and ICAM-1 mRNA were decreased in group AMB (P<0.05).Conclusion Ambroxol can attenuate sepsis-induced lung injury probably through inhibiting p38 mitogen-activated protein kinase pathway in mice.
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Objective To evaluate the effect of γ-aminobutyric acid (GABA) preconditioning on pathological stretch-induced damage to type Ⅱ alveolar epithelial cells by mechanical ventilation.Methods A549 cells cultured in vitro (0.2× 106/ml,2.5 ml/well) were randomly divided into 3 groups using a random number table:control group (group C),pathological stretch group (group P) and GABA preconditioning+pathological stretch group (group G).A549 cells were exposed to 20% cyclic stretch at 0.3 Hz for 6 h in groups P and G;GABA 50 μmol/L was given 30 min before cyclic stretch in group G.After the end of pathological stretch,the cells were collected for determination of the cell viability by methyl thiazolyl tetrazolium assay and lactate dehydrogenase (LDH) release by colorimetricmethod;the expression of F-actin was observed with indirect immunofluorescence;the expression of Rho-associated kinase 1 (ROCK1) and GABAAR were determined by western blot.Results Compared with group C,the cell viability was significantly decreased,the amount of LDH released was increased,the expression of ROCK1 was significantly increased and the expression of GABAAR was significantly decreased in groups P and G (P<0.05);Compared with group P,the cell viability was significantly increased,the amount of LDH released was decreased,F-actin was re constructed,the expression of ROCK1 was significantly decreased and the expression of GABAAR was significantly increased (P<0.05) in group G.The reconstruction of F-actin in group P was better than that in group G and worse than that in group C.Conclusion GABA preconditioning can attenuate pathological stretch-induced damage to type Ⅱ alveolar epithelial cells probably through up regulating the expression of GABAA receptor.
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Objective To evaluate the effect of ventilation with different positive end-expiratory pressures (PEEPs) on intracranial pressure in the patients undergoing gynecological laparoscopic surgery.Methods Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 25-55 yr,with body mass index of 18-27 kg/m2,scheduled for elective gynecological endoscopic surgery,were divided into 3 groups (n=20 each) using a random number table method:routine ventilation group (group A),4 cmH2O PEEP group (group B) and 8 cmH2O PEEP group (group C).The patients were mechanically ventilated with PEEP 4 or 8 cmH2O at 5 min of head-down tilt after start of pneumoperitoneum in group B and group C.The patients were mechanically ventilated in volume-controlled mode,with tidal volume 7 ml/kg,inspired oxygen concentration 50% and inspiratory/expiratory ratio 1 ∶ 2.Blood samples were collected from the radial artery for measurement of PaCO2 and PaO2 at 5 min after tracheal intubation (T0),5,15 and 30 min of head-down tilt (T1-3),and 5 min of the supine position after the end of pneumoperitoneum (T4).The peak airway pressure (Ppeak) was recorded,dynamic pulmonary compliance (Cdyn)was calculated,and optic nerve sheath diameter was measured using an ultrasonic apparatus at T0-4.Cognitive function was assessed at 1 day before surgery and 7 days after surgery using Mini-Mental State Examination.Results Compared with group A,Ppeak was significantly increased at T1-4,and PaO2 was increased at T2 in group B,and Ppeak and PaO2 were increased at T1-4,and Cdyn was increased at T1,2 in group C (P<0.05).Compared with group B,Ppeak was significantly increased at T4,and Cdyn was increased at T2 in group C (P<0.05).There was no significant difference in optic nerve sheath diameter or Mini-Mental State Examination score at each time point among three groups (P>0.05).No patients developed cognitive dysfunction at 7 days after surgery in three groups.Conclusion Ventilation with different PEEPs causes no increase in intracranial pressure of the patients undergoing gynecological laparoscopic surgery.
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Objective To evaluate the accuracy of variation of the end-tidal pressure of carbon dioxide (△PETCO2) in predicting the fluid responsiveness in patients undergoing resection of gastrointestinal tumor.Methods Forty-six patients of both sexes,aged 40-64 yr,with body mass index of 20-24 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing elective resection of gastrointestinal tumor with general anesthesia,were enrolled in the study.When the change in mean arterial pressure was less than 10% within 5 min after anesthesia induction,250 ml Ringer's solution was rapidly infused over 10 min via the peripheral vein.Increase in cardiac index after volume expansion ≥ 15% was considered to be a positive response.The receiver operating characteristic curve for △PETCO2 in determining fluid responsiveness was drawn.Results The results of receiver operating characteristic curve analysis showed that the area under the curve for △PETCO2 in determining fluid responsiveness (95% confidence interval) was 0.826 (0.730-0.942,P<0.05),the critical value 21.9%,sensitivity 76.5%,specificity 90.9%.Conclusion △PETCO2 can accurately predict the fluid responsiveness in patients undergoing resection of gastrointestinal tumor.
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Objective To evaluate the changes in the expression of c-fos protein in the spinal cord in a rat model of oxycodone dependence or withdrawal response.Methods Thirty SPF adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 180-220 g,were divided into 3 groups (n=10 each) using a random number table method:normal saline group (group NS),oxycodone dependence group (group OD),and oxycodone withdrawal group (group OW).In OD and OW groups,oxycodone was injected subcutaneously in back,5 days in total,with the dose of 2,3,4,5 and 6 mg/kg in turn,3 times a day (8:00/15:00/22:00).The equal volume of normal saline was given instead in group NS.The mechanical paw withdrawal threshold was measured at 3 days before administration and 30 min after the last administration every day.The oxycodone withdrawal was induced by intraperitoneal injection of naloxone 4 mg/kg at 8 h after the last administration of oxycodone on 5th day in group OW.The withdrawal response scores and range of weight changes were recorded within 15 min after giving naloxone or normal saline in NS and OW groups.Spinal cord tissues were collected at 1 h after the last administration on 5th day in group OD and at 1 h after giving normal saline or naloxone on 5th day in NS and OW groups for determination of the expression of c-fos protein by Western blot.Results Compared with group NS,the mechanical paw withdrawal threshold was significantly increased on 1 and 2 days after administration,and the expression of c-fos protein in the spinal cord was up-regulated in OD and OW groups,and withdrawal response scores were significantly increased,and the range of weight change was increased in group OW (P<0.05).The expression of c-fos protein was significantly down-regulated in group OW as compared with group OD (P<0.05).Conclusion Oxycodone dependence or withdrawal response may be related to the expression of c-fos protein in the spinal cord of rats,and the expression is up-regulated during oxycodone dependence,while down-regulated during oxycodone withdrawal.
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Objective To evaluate the changes in activation of γ?aminobutyric acid(GABA)sig?naling pathway during ventilator?induced brain injury in rats. Methods Thirty?six pathogen?free adult male Sprague?Dawley rats, weighing 280-320 g, were divided into 3 groups(n=12 each)using a random number table: low tidal volume group(LV group), ventilation with high tidal volume for 2 h group(HV1 group)and ventilation with high tidal volume for 6 h group(HV2group). The rats were mechanically ven?tilated for 2 h with the tidal volume set at 10 ml∕kg and the respiratory rate 40 breaths∕min in group LV. The rats were mechanically ventilated for 2 h with the tidal volume set at 40 ml∕kg and the respiratory rate 40 breaths∕min in group HV1. The rats were mechanically ventilated for 6 h with the tidal volume set at 40 ml∕kg and the respiratory rate 40 breaths∕min in group HV2. Blood samples were collected at the end of ven?tilation for determination of serum neuron?specific enolase(NSE)and S100β protein concentrations by en?zyme?linked immunosorbent assay. Six rats were then sacrificed and their brains were removed for determi?nation of interleukin?1β(IL?1β)and tumor necrosis factor?α(TNF?α)contents(by enzyme?linked im?munosorbent assay)and expression of glutamic acid decarboxylase(GAD)and GABAAreceptors(by Western blot). Morris water maze test was performed on 2nd day after the end of ventilation. Results Compared with group LV, the serum concentrations of NSE and S100β protein and contents of IL?1β and TNF?α were significantly increased, the expression of GAD and GABAAreceptors was up?regulated, the es?cape latency was prolonged, and the percentage of swimming distance at the original platform was decreased in HV1and HV2groups(P<0.05). Compared with group HV1, the serum concentrations of NSE and S100β protein and contents of IL?1β and TNF?α were significantly increased, the expression of GAD and GABAAreceptors was up?regulated, the escape latency was prolonged, and the percentage of swimming distance at the original platform was decreased in group HV2(P<0.05). Conclusion Activation of GABA signaling pathway is enhanced during ventilator?induced brain injury, which may be involved in the patho?physiological mechanism of ventilator?induced brain injury in rats.
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Objective To investigate the effect of Shenfu injection preconditioning on ventilator-induced brain injury in rats.Methods Sixty healthy adult male Sprague-Dawley rats,weighing 300-320 g,were divided into 3 groups (n=20 each) using a random number table:control group (group C),ventilator-induced brain injury group (group VIBI) and Shenfu injection group (group SF).Rats were mechanically ventilated for 6 h with tidal volume of 40 ml/kg in VIBI and SF groups.Rats were mechanicaliy ventilated for 6 h with tidal volume of 10 ml/kg in group C.Shenfu injection 20 ml/kg was injected intraperitoneally at 30 min before ventilation in group SF.Blood samples were collected at 2 and 6 h of ventilation for measurement of the concentrations of serum S100β protein (by enzyme-linked immunosorbent assay).Then the rats were sacrificed at the end of ventilation,and brains were removed for determination of the contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-o) (by enzyme-linked immunosorbent assay) and expression of glutamate decarboxylase (GAD) and γ-aminobutyric acid type A (GABAA) receptor in brain tissues (by Westem blot).Results Compared with group C,the serum concentrations of S100β protein at each time point of ventilation and contents of IL-1β and TNF-α in brain tissues were significantly increased,and the expression of GAD and GABAA receptor was down-regulated in VIBI and SF groups (P<0.05).Compared with group VIBI,the serum concentrations of S100β protein at each time point of ventilation and contents of IL-1β and TNF-α in brain tissues were significantly decreased,and the expression of GAD and GABAA receptor was up-regulated in group SF (P<0.05).Conclusion Shenfu injection preconditioning can relieve ventilator-induced brain injury in rats,and the mechanism may be related to inhibiting inflammatory responses and activating GABA signaling pathway.
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Objective To evaluate the effect of mechanical stretch preconditioning on pathological stretch-induced activation of γ-aminobutyric acid (GABA) signaling pathway in human type Ⅱ alveolar epithelial cells (AEC Ⅱ).Methods AEC Ⅱ cell line (A549 cells) culturedin vitro were divided into control group (group C), pathological stretch group (group P1) and mechanical stretch preconditioning group (group P2). In group C, A549 cells were cultured routinely. In group P1, A549 cells were exposed to 20% cyclic stretch for 6 hours. In group P2, A549 cells were exposed to 5% cyclic stretch for 60 minutes, and then exposed to 20% cyclic stretch for 6 hours. The cells were harvested for determination of the cell viability by methyl thiazolyl tetrazolium assay, lactate dehydrogeuase (LDH) release was determined by colorimetric method, the levels of interleukin (IL-1β and IL-6) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA), the mRNA expressions of IL-1β, IL-6 and TNF-α were determined by reverse transcription-polymerase chain reaction (RT-PCR), and the protein expressions of glutamic acid decarboxylase (GAD) and γ-aminobutyric acid A receptor (GABAAR) were determined by Western Blot.Results Compared with group C, the cell viability of group P1 was significantlydecreased (A value: 0.196± 0.071 vs. 0.886±0.107), the release rate of LDH was significantly increased [(12.3±2.4)% vs. (1.9±0.5)%]; the contents and mRNA expressions of IL-1β, IL-6 and TNF-α in cell culture medium were significantly increased [IL-1β (ng/L): 138.6±19.7 vs. 32.7±7.4, IL-6 (ng/L): 196.5±31.7 vs. 55.4±13.8, TNF-α (ng/L): 111.3±21.8 vs. 20.8±7.6; IL-1β mRNA (2-ΔΔCT): 2.79±0.44 vs. 0.83±0.12, IL-6 mRNA (2-ΔΔCT): 1.99±0.25 vs. 0.56±0.11, TNF-α mRNA (2-ΔΔCT): 2.54±0.37 vs. 0.72±0.09]; the protein expressions of GAD and GABAAR were significantly decreased [GAD (gray value): 0.38±0.12 vs. 1.75±0.45, GABAAR (gray value): 0.29±0.09 vs. 1.68±0.39; allP < 0.05]. Compared with group P1, the cell viability of group P2 was significantly increased (A value: 0.523±0.132 vs. 0.196±0.071),the release rate of LDH was significantly decreased [(6.9±1.7)% vs. (12.3±2.4)%]; the contents and mRNA expressions of IL-1β, IL-6 and TNF-α in cell culture medium were significantly decreased [IL-1β (ng/L): 79.2±11.6 vs. 138.6±19.7, IL-6 (ng/L): 89.6±15.6 vs. 196.5±31.7, TNF-α (ng/L): 55.9±11.4 vs. 111.3±21.8; IL-1β mRNA (2-ΔΔCT): 1.92±0.36 vs. 2.79±0.44, IL-6 mRNA (2-ΔΔCT): 1.09±0.18 vs. 1.99±0.25, TNF-α mRNA (2-ΔΔCT): 1.77±0.25 vs. 2.54±0.37]; the protein expressions of GAD and GABAAR were significantly increased [GAD (gray value): 1.26±0.33 vs. 0.38±0.12, GABAAR (gray value): 1.04±0.15 vs. 0.29±0.09; allP < 0.05]. Conclusion The mechanism by which mechanical stretch preconditioning attenuates pathological stretch-induced injury in human AECⅡ is related to the activation of GABA signaling pathway.
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Objective To evaluate the effect of ulinastatin on γ-aminobutyric acid (GABA) signal pathway in mice with ventilator-induced lung injury (VILI).Methods Thirty-six male Wister mice were randomly divided into 3 groups using a random number table:control group (group C), ventilator-induced lung injury group (group VILI),and ventilator-induced lung injury+ ulinastatin group (group UTI),n =12 in each group.VILI was induced by 4 h mechanical ventilation with tidal volume 40 ml/kg in groups VILI and UTI.Ulinastatin 1×10 5 U/kg was injected intraperitoneally 1 h before ventilation in group UTI,while the equal volume of normal saline was given in groups C and VILI.The mice were then sacrificed,the left lung was lavaged,and broncho-alveolar lavage fluid (BALF)was collected for determination of concentrations of protein,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and intercellular adhesion molecule-1 (ICAM-1).The lung tissues were re-moved for determination of the wet to dry lung weight (W/D)ratio,the mRNA expression level of IL-1β,TNF-αand ICAM-1.The pathological changes of the lungs were determined under light micro-scope and the lung injury scores were also determined.Immunohistochemistry and Western blot were used to detected the protein expression level of GAD and GABAA R.Results The W/D ratio (6.7 ± 2.4 vs.8.5±2.3)and lung scores [(6.9±2.3)scores vs.(1 1.8±2.7)scores]were significantly de-creased in group UTI than those in group VILI.The concentrations of IL-1β[(56±1 1)ng/L vs.(77 ±1 5)ng/L],TNF-α[(105±29)ng/L vs.(1 58±37)ng/L]and ICAM-1 [(205±46)ng/L vs.(293 ±61)ng/L]in BALF in group UTI were significantly decreased than those in group VILI.The mRNA ex-pression levels of IL-1β(1.81±0.26 vs.2.58±0.34),TNF-α(1.61±0.15 vs.2.94±0.27)and ICAM-1 (1.74±0.27 vs.2.79±0.31)were significantly decreased in group UTI than those in group VILI.The protein expression levels of GAD (0.44±0.08 vs.0.18 ±0.04)and GABAA R (0.30 ±0.09 vs.0.15 ± 0.04)were significantly increased in group UTI than those in group VILI.Conclusion Ulinastatin can at-tenuate VILI probably through activating GABA signaling pathway.
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Objective To investigate the application of myocardial protection technique in off-pump coronary artery bypass grafting (CABG) combined with valve surgery.Methods Forty-five patients who received CABG combined valve surgery in the cardiothoracic surgery department of our hospital from February 2015 to March 2017 were as the research object.All of the patients were treated by myocardial protection technique in off-pump CABG combined with valve surgery.The preoperative and postoperative heart function rating and color ultra results and surgical patients discharged to evaluate the method.Results There was no difference in left ventricular ejection fraction before and after surgery(P > 0.05).left ventricular end diastolic diameter and left atrial end diastolic diameter at 7 days after operation was significantly lower than those before operation,the differences were significant (P < 0.05).After followed up for 3 months,the level Ⅰ and level Ⅱof cardiac function increased significantly in 29 cases,heart function classification(NYHA) after 3 months was significantly better than that before the surgery,the difference was significant(P < 0.05).Mediastinal infection occurred in 1 case and poor healing of wound in 1 case,healing after active treatment.Conclusion Myocardial protection technique in off-pump CABG combined with valve surgery plays an important role in the whole surgical process and ensures the operation effect.
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Objective To study the association of Hp infection and insulin resistance (IR) with vascular dementia (VaD).Methods Eighty-six elderly VaD patients admitted to our hospital from April 2015 to April 2016 served as a VaD group and 52 healthy subjects undergoing physical examination served as a control group in this study.The patients in VaD group were further divided into Hp-positive group (n =50) and Hp-negative group (n =36).Their fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured with positive C13 urea breath test as the diagnostic index of Hp infection.HOMA-IR=FINS× FBG/22.5 was calculated according to the self balance model analysis.Results The positive Hp rate,serum FBG and FINS levels,and HOMA-IR were significantly higher in VaD group than in control group (58.14% vs 28.58%,x2=10.273,P=0.002;5.53±0.60 mmol/L vs 5.19±0.38 mmol/L,P=0.0004;10.29±4.95 μIU/L vs 8.77±4.02 μIU/L,P=0.0317;2.57±1.34 vs 2.06±0.96,P=0.0179).The serum FBG and FINS levels and HOMA-IR were significantly higher in Hp-positive group than in Hp-negative group (P<0.05,P<0.01).Conclusion Hp infection and IR are closely associated with VaD,and can thus lead to the occurrence or progression of VaD by inducing or aggravating IR.
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Objective To evaluate the relationship between the shedding of syndecan-4(SDC-4) in lung tissues and ventilator-induced lung injury in rats. Methods Thirty pathogen-free healthy adult male Wistar rats, weighing 220-250 g, were divided into 3 groups(n=10 each)using a random number table:control group(group C), mechanical ventilation with traditional tidal volume(VT)group(group T-VT) and mechanical ventilation with high VTgroup(group H-VT). The animals were anesthetized with pento-barbital sodium and tracheostomized. The rats kept spontaneous breathing in group C. The rats were me-chanically ventilated for 4 h with the VTset at 6 ml∕kg in group T-VT and with the VTset at 40 ml∕kg in group H-VT. Blood samples were collected immediately after the end of ventilation for measurement of serum SDC-4 concentrations by enzyme-linked immunosorbent assay. The left lung was lavaged, and broncho-alveolar lavage fluid was collected for determination of interleukin-1beta(IL-1β), IL-18, tumor necrosis factor-alpha and SDC-4 concentrations by enzyme-linked immunosorbent assay. The lungs were removed for determination of the wet to dry weight ratio and expression of SDC-4 protein and mRNA in lung tissues(by Western blot and real-time polymerase chain reaction, respectively)and for examination of the pathological changes. The lung injury scores were recorded. Results Compared with group C, the wet to dry weight ratio, lung injury scores, concentrations of IL-1β, IL-18, tumor necrosis factor-alpha and SDC-4 in bron-cho-alveolar lavage fluid and concentrations of SDC-4 in serum were significantly increased, the expression of SDC-4 mRNA was up-regulated, and the expression of SDC-4 was down-regulated in group H-VT(P<005), and no significant change was found in the parameters mentioned above in group T-VT(P>005).Marked pathological changes of lung tissues were found in group H-VT. Conclusion A large shedding of SDC-4 in lung tissues may be involved in the pathophysiological mechanism of ventilatior-induced lung injury in rats.
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Objective To evaluate the effect of dexmedetomidine on the expression of gamma-aminobutyric acid(GABAA)receptors during ventilator-induced lung injury(VILI)in rats. Methods Thirty pathogen-free adult male Sprague-Dawley rats,weighing 280-320 g,were divided into 3 groups(n=10 each)using a random number table:control group(group C),group VILI and dexmedetomidine group(group Dex).The rats were mechanically ventilated for 4 h with the tidal volume of 40 ml/kg to establish VILI model. Dexmedetomidine 50 μg/kg was injected intraperitoneally after the rats were anesthetized in group Dex,while the equal volume of normal saline was given instead in C and VILI groups. The animals were sacrificed at 4 h of mechanical ventilation,the lungs were removed for examination of pathological changes which were scored,bronchoalveolar lavage fluid(BALF)was collected for determination of concentrations of total protein,interleukin-1 beta(IL-1β),IL-6 and tumor necrosis factor-alpha(TNF-α),and the lung specimens were obtained for determination of the wet/dry weight ratio(W/D ratio),alveolar fluid clearance(AFC)and expression of GABAA receptors,IL-1β,IL-6 and TNF-α mRNA in lung tissues. Results Compared with group C,the W/D ratio,pathological scores,expression of total protein,IL-1β,IL-6 and TNF-α in BALF and expression of IL-1β,IL-6 and TNF-α mRNA in lung tissues were significantly increased,and the GABAA receptor expression and AFC were decreased in VILI and Dex groups(P<0.05).Compared with group VILI,the W/D ratio,pathological scores,expression of total protein,IL-1β,IL-6 and TNF-α in BALF and expression of IL-1β,IL-6 and TNF-α mRNA in lung tissues were significantly decreased,and the GABAA receptor expression and AFC were increased in group Dex(P<0.05).Conclusion The mechanism by which dexmedetomidine reduces VILI is related to up-regulation of GABAA receptor expression in rats.
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Objective To evaluate the effect of dexmedetomidine on microRNA (miRNA)-155-hypoxia-inducible factor-1α (HIF-1α)-heme oxygenase-1 (HO-1) signaling pathway in a rat model of endotoxin-induced acute lung injury.Methods Forty adult male Wistar rats,weighing 220-250 g,were equally and randomly divided into 4 groups using a random number table:control group (group C),dexmedetomidine group (group D),endotoxin-induced acute lung injury group (group L),and endotoxin-induced acute lung injury+dexmedetomidine group (group LD).Acute lung injury was induced by intraperitoneal lipopolysaccharide (LPS) 5 mg/kg in L and LD groups.In D and LD groups,dexmedetomidine was infused in a loading dose of 1 μg · kg-1 · h-1 for 10 min starting before intraperitoneal injection of normal saline or LPS followed by an infusion of 5 μg · kg-1 · h-1 throughout the operation.At 6 h after normal saline or LPS injection,blood samples were taken from the carotid artery for detection of arterial oxygen partial pressure (PaO2).The left lung was lavaged,and broncho-alveolar lavage fluid (BALF) was collected for determination of concentrations of total protein,interleukin-1β (IL-1β),tumor necrosis factor-α (TNF-α),and intercellular adhesion molecule-1 (ICAM-1).The rats were then sacrificed,and lungs were removed for determination of the wet to dry lung weight ratio (W/D ratio),mRNA expression of miR-155,IL-1β,TNF-α and ICAM-1,and protein expression of HIF-1α and HO-1,and for examination of the pathological changes which were scored.Results Compared with group C,the PaO2 was significantly decreased,and the W/D ratio,lung injury score,concentrations of total protein,IL-1β,TNF-α and ICAM-1 in BALF,mRNA expression of miR-155,IL-1β,TNF-α and ICAM-1,and protein expression of HIF-1α and HO-1 were significantly increased in L and LD groups (P < 0.05).Compared with group L,the PaO2 and protein expression of HIF-1α and HO-1 were significantly increased,and the W/D ratio,lung injury score,concentrations of total protein,IL-1β,TNF-α and ICAM-1 in BALF,and mRNA expression of miR-155,IL-1β,TNF-α and ICAM-1 were significantly decreased in group LD (P<0.05).Conclusion Dexmedetomidine reduces endotoxin-induced acute lung injury through activating miR-155-HIF-1α-HO-1 signaling pathway in rats.