Objective To investigate the changes of the expression of HIF-1α (hypoxia induciblefactor-1a) mRNA in myocardium of rats after cardiopulmonary resuscitation (CPR) and the intervention effects of exogenous hydrogen sulfide on it. Method Forty five male SD rats were randomly divided into three groups: control group ( n = 15 ), cardiopulmonary resuscitation group ( CPR group, n = 15 ) and NaHS + CPR group (n = 15 ) . Rats of control group were anesthetized and intubated without asphyxia and cardiac arrest. The rats of CPR group and NaHS + CPR group were operated to induce cardiac arrest by asphyxiation. In the rats of NaHS + CPR group, NaHS in dose of 50 ug/kg was administrated via the femoral venous line 1 minute before CPR. Hemodynamic was monitored continuously. The expression of HIF - lα mRNA in myocardium of rats in each group was determined by using RT-PCR and the activity of myeloperoxidase (MPO) in the myocardium of rats in each group was assayed by using a patent reagent box 6 h after CPR. The histopathological changes of myocardium were also observed. The t- test was used for statistical analysis. Results There was no statistically significant difference in hemodynamic changes between CPR group and CPR + NaHS group ( P ＞ 0. 05 ) . When compared with the control group, the activity of MPO and the expression of HIF-1α mRNA in CPR group and CPR + NaHS group were both increased, and those increased in CPR + NaHS group was more significant (P ＜ 0. 05) . When compared with CPR group, the expression of HIF-1α mRNA in CPR + NaHS group was higher, however, the activity of MPO in CPR + NaHS group was lower ( P ＜ 0. 05) . There were various histopathological changes of myocardium of rats found in CPR group and CPR + NaHS group, and the damage of myocardium of rats in CPR group was more obvious than that in CPR + NaHS group. Conclusions The expression of HIF-1α mRNA in myocardium of rats was increased after CPR. Exogenous hydrogen sulfide can protect myocardium cells from resuscitation-perfusion injury, and the protection is associated with increase in expression of HIF 1 αmRNA.

Objective To investigate the effects of hydrogen sulfide on sepsis-induced cardiac dysfunction in rats.Methods Male SD rats were randomly ( random number) divided into 4 groups:control group ( Ⅰ group),sepsis group ( Ⅱ group),sepsis + NaHS group (Ⅲ group),sepsis + PAG group (Ⅳ group). Cecal ligation and puncture technique was used in Ⅱ, Ⅲ, Ⅳ group. Hemodynamic was observed,and H2S synthesis,CSE (cystathionine-r-lyase) mRNA,MPO activity and the level of TNF-α,IL-1β were determined.The morphological changes and infiltration of inflammatory cells in myocardium were also observed.Results Compared with Ⅰ group,H2S synthesis,the levels of TNF-α,IL-1 β,the activity of MPO increased ( P ＜ 0.05 or P ＜ 0.01 ),and the expression of CSE-mRNA increased,and blood pressure of rats decreased significantly in Ⅱ group.Compared with Ⅱ group,H2S synthesis,the levels of TNF-α,IL-1β and the activity of MPO increased (P ＜ 0.05),the expression of CSE mRNA did not change noticeably ( P ＞ 0.05),and blood pressure of rats decreased more significantly in Ⅲ group.Compared with Ⅱ group, H2S level decreased,the levels of TNF-α,IL-1β and the activity of MPO decreased significantly,the expression of CSE mRNA decreased and blood pressure of rats decreased in Ⅵ group (P ＜0.05).Histopathological changes of myocardium were aggravated in the following severity order: Ⅰ ＜ Ⅳ ＜＜ Ⅲ.Conclusions CSE/H2S system of the myocardium was upregulated in sepsis rats.Hydrogen sulfide could raise the levels of MPO,TNF-α,IL-1β,aggravating myocardial injury. Contrarily,the inhibitor of H2S could counteract it.

To investigate the interaction and involvement of sodium hydrosulfide (NaHS), a H(2)S donor, on hippocampus of rats suffering from sepsis-associated encephalopathy, rats were subjected to cecal ligation and puncture (CLP)-induced sepsis. Adult male Sprague-Dawley rats were randomly divided into four groups: Sham group, CLP group, CLP+NaHS group and CLP+aminooxyacetic acid (AOAA, an inhibitor of H(2)S formation) group. The four groups were observed at 3, 6, 9, 12 h after treatment. We examined hippocampal H(2)S synthesis and the expression of cystathionine-β-synthetase (CBS), a major enzyme involved in the H(2)S synthesis in hippocampus. CBS expression was detected by reverse transcription polymerase chain reaction (RT-PCR). The concentrations of inflammatory cytokines (TNF-α, IL-1β) were determined in hippocampus by using enzyme-linked immunosorbent assay (ELISA). Neuronal damage was studied by histological examination of hippocampus. In CLP group, H(2)S synthesis was significantly increased in hippocampus compared with sham group and it peaked 3 h after CLP (P<0.05). Sepsis also resulted in a significantly upregulated CBS mRNA in hippocampus. The levels of TNF-α and IL-1β in the hippocampus were substantially elevated at each time point of measurement (P<0.05), and they also reached a peak value at about 3 h. Administration of NaHS significantly aggravated sepsis-associated hippocampus inflammation, as evidenced by TNF-α and IL-1β activity and histological changes in hippocampus. In septic rats pretreated with AOAA, sepsis-associated hippocampus inflammation was reduced. It is concluded that the rats subjected to sepsis may suffer from brain injury and elevated pro-inflammatory cytokines are responsible for the process. Furthermore, administration of H(2)S can increase injurious effects and treatment with AOAA can protect the brain from injury.

Objective To discuss the jointly therapeutic effects of 6％ hydroxyethyl starch 130/0.4 (voluven) and furosemide on acute lung injury induced by paraquat (PQ) in swine.Methods The ALI/ ARDS models were established with 20％ PQ (20 mL) intraperitoneal injection in 18 healthy female piglets and randomly divided into three groups: voluven group (A), furosemide group (B) and voluven + furosemide group (C) (n =6 in each group).The heart rate (HR), mean arterial pressure (MAP), extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), partial pressure of carbon dioxide (PaCO2) and oxygenation index (PaO2/FiO2) among the three groups were carefully measured by PICCO (pulse indicator continuous cardiac output) before modeling (baseline), just aftermodeling (t0), and 2 h (t2), 4 h (t4), 6 h (t6) and 8 h (t8) after trearment.Needle biopsies of lung tissue were made before modeling and at t0 and t8 and prepared for microscopy observation after Hematoxylineosin staining method (HE staning).Repeated measurement data were compared among repeated measures by the ANOVA and the difference between groups was compared by one-wey ANOVA.Results (1) The HR and MAP of all animals increased obviously while the oxygenation index declined significantly at modeling just made (t0) compared to those before modeling (all P ＜ 0.05).At the same time, the HR and MAP of A and B groups were significantly lower than those of C group after treatment (all P ＜ 0.05), while the oxygenation index of A and B were significantly higher (all P ＞ 0.05).(2) The ELWI and PVPI of all animals increased obviously at modeling just made (t0) compared to those before modeling (all P ＜ 0.05).The ELWI and PVPI were decreased after treatment.And at the same time, the ELWI and PVPI of A and B groups were significantly lower than those of C group after treatment (all P ＜ 0.05).(3) The alveolar tissue showed obviously injured changes at modeling just made (t0).The injury was relieved 8h after trearment, which was most markedly in group C.Conclusions With the combination of 6％ hydroxyethyl starch 130/0.4 and furosemide administered, the acute lung injury induced by paraquat poisoning can be effectively relieved, promoting gas exchange, and improve oxygenation.

Objective To detect the expression of CD 44 +/CD24 -and E-cadherin and vimentin in non-small cell lung cancer and its clinical prognostic relevance .Methods By immunohistochemistry , detecting , 500 cases of non-small cell lung cancer E -cadherin ,Vimentin and CD44 +/CD24 -expressions′correlation ,we analyzed the relationship with non -small cell lung cancer .Results In non-small cell lung cancer , vimentin was related to tissue differentiation,TNM staging(P<0.05);there was relationship between CD44 +/CD24 -and EMT by E-cadherin expression(P <0.05);CD44 +/CD24 -expression was related to lymph node metastasis , differentiation(P<0.05);their expressions were not obviously related to age ,sex,smoking history,clinical patho-logical type .The survival time of CD44 +/CD24 -high expression in NSCLC was significantly shorter than lower expression in NSCLC(P<0.05).Conclusion EMT malignant phenomenon raises cancer stem cells ,which can lead to the development of malignant cells poorly differentiated trends ,they are not an isolated process;important role in the development of EMT and CD 44 +/CD24 -union occurs in non -small cell lung cancer and prognosis with patients ,which provides a potential breakthrough in the treatment of cancer prevention and treatment targets .

Objective:To observe effect of Xiaoyu Zhixue Tablets on expression of platelet membrane glucoprotein in the patient of hemorrhagic thrombopathy and probe into the mechanism of the therapy.Methods:148 cases of hemorrhagic thrombopathy were randomly divided into a Chinese drug group(n=98)treated by Xiaoyu Zhixue Tablets,and a Western medicine group(n=50) treated by adrenosem,vitamine C,K,P.They were treated for 6 months.After treatment the therapeutic effect of hemostasis and the recovery rate of platelet aggregation in the two group were observed and analyzed.Before and after treatment expressions of platelet membrane glucoproteins GP Ⅰ b/Ⅸ,GP Ⅱ b/Ⅲa,GP Ⅰ b,GP Ⅱ b,GP Ⅲ a and p-selectin expression were detected with flow cytometry in the two groups and in 34 healthy persons(normal group).Results:The total effecive rate of hemostasis was 89. 8% in the Chinese drug group and 54.0% in the Western medicine group,and the recovery rate of platelet aggegation was 72.4% in the Chinese drug group and 4.0% in the Western medicine group,with significant differences(both P0.05).Conclusion:Xiaoyu Zhixue Tablets can up-regulate platelet membrane glucoproteins GP Ⅰ b/Ⅸ,GP Ⅱ b/Ⅲ a,GP Ⅰ b,GP Ⅲ a and p-selectin expression,which is possibly one of the mechanisms for treatment of hemorrhagic thrombopathy.

Objective To investigate the effect of neutral amino acid on preventing Parkinson disease.Methods Mice were injected with L-Valine,L-Pheylalanine,D-Valine or L-Lysine before or after paraquat administration,by which prakinsonian mouse model was constructed.The paraquat immunoreactivity was observed within nigral cell bodies.Then neurodegeneration and ?-synuclein aggregation were observed by immunohistochemistry and Western blot.Results Paraquat immunoreactivity was abolished by the administration of L-Valine,L-Pheylalanine before paraquat exposure.Pre-treatment with these two amino acids also protected the paraquat-induced loss of nigrostriatal dopaminergic cells and formation of thioflavine S-positive aggregates.In contrast, paraquat-induced toxicity was unaffected if animals were injected with these two amino acids after paraquat exposure or pre-treated with D-Valine or L-Lysine.Conclusions L-type neutral amino acids such as L Valine and L-Pheylalanine can prevent paraquat-induced neurodegeneration and a synuclein pathology through a competitive inhibition mechanism with stereospecificity in the central nervous system (CNS).Neutral amino acid could protect the dopaminergic neuron in substantia nigra and may prevent Parkinson disease.

Gene Expression Profiling ; Humans ; Killer Cells, Natural ; pathology ; Lymphoma, T-Cell ; genetics ; metabolism ; pathology ; Nose Neoplasms ; genetics ; metabolism ; pathology ; Oligonucleotide Array Sequence Analysis ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics

This study was performed to determine the metabolic profile of four amide synthetic cannabinoids that recently abused, i.e., ADB-4en-PINACA, 4CN-CUMYL-BUTINACA, 5F-EMB-PICA and 4F-MDMB-BUTICA, in human liver microsomes (HLMs). The four amide synthetic cannabinoids were added to the microsomal incubation model, being incubated for 10 min, 60 min or 3 h to simulate human hepatic metabolism.Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analytical instrument was employed to determine and speculate the structure of phase I metabolites and their possible metabolic pathways.The results showed that there were 27 phase I metabolic pathways for the four amide synthetic cannabinoids, including hydroxylation, carboxylation, N-dealkylation and ester hydrolysis, with the main phase I metabolic pathways of ester hydrolysis, dihydrodiol (pentenyl tail), oxidative defluorination to carboxylic acid, monohydroxylation (alkyl side chain or indole/indazole ring) and N-dealkylation.The results of this study may provide potential detection markers for forensic identification and sewage abuse assessment of the four amide synthetic cannabinoids.

AIM:To describe the dynamic characteristics of mitochondria in the development of mouse embryonic hematopoietic stem cells,and to explore the function of mitochondria in this process.METHODS:Single-cell transcrip-tomic data of continuous developmental hematopoietic stem cell-related populations were analyzed to describe the dynamic changes of genes related to mitochondrial synthesis and energy metabolism.To explore the dynamic changes in the number and activity of mitochondria during the development of hematopoietic stem cells,we detected the mitochondrial number and mitochondrial membrane potential of the cells in each stage of hematopoietic stem cell development by fluorescent probe staining combined with flow cytometry.We added small molecule inhibitors of mitochondrial synthesis and energy metabolism and used hematopoietic cell colony formation assay to detect the effect of mitochondrial function inhibition on the induction of hematopoietic products in vitro.RESULTS:(1)Single-cell transcriptome analysis showed that genes in-volved in mitochondrial synthesis and oxidative phosphorylation were significantly up-regulated in endothelial cell and type Ⅰ pre-hematopoietic stem cell compared with those involved in glycolysis,and these genes could significantly distinguish continuous dynamic populations.(2)The results of fluorescence staining and flow cytometry analysis showed that mito-chondrial number and mitochondrial membrane potential had an increasing trend during the continuous development of he-matopoietic stem cell,reaching the highest level in the precursor stage of type 2 pre-hematopoietic stem cell,and decreasing in the mature hematopoietic stem cell of fetal liver.(3)Compared with control group,inhibition of mitochondrial respirato-ry chain Ⅰ and Ⅴ significantly reduced the number of hematopoietic colonies(P<0.05).CONCLUSION:(1)Genes re-lated to mitochondrial synthesis and oxidative phosphorylation are highly expressed in hemogenic endothelial cells and type Ⅰpre-hematopoietic stem cells,and can be used to distinguish continuous developing populations.(2)The mitochondrial number and mitochondrial membrane potential increased continuously during hematopoietic stem cell development and reached the highest level in type 2 pre-hematopoietic stem cells.(3)Inhibition of mitochondrial respiratory chain Ⅰ and Ⅴ significantly reduced the production of hematopoietic products in vitro.