Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective:To explore the effect of SimMan 3G simulator based scenario simulation teaching method and case-based learning (CBL) in emergency medicine teaching.Methods:Sixty students from Batch 2013 eight-year program of clinical medicine were selected as subjects. They were randomly divided into an experimental group and a control group, with 30 students in each group. In the teaching of emergency medicine, the experimental group used the combination of scenario simulation with CBL teaching methods, and the control group used classic teaching methods. The test scores and the questionnaires satisfaction of the two groups were compared to evaluate the teaching effects. SPSS 17.0 was used for the statistical analysis, measurement data were compared between the groups by t test, and counting data were compared between groups by chi-square test.Results:The scores of the experimental group (94.24±1.13) were better than those of the control group (90.6±0.59), with significant differences ( t=12.85, P<0.05). The results of the questionnaires showed that the students of experimental group were more satisfied with the learning experience than those of the control group. Conclusion:The teaching method can improve the teaching effects, the students' emergency clinical thinking, skills, comprehensive analysis and judgment ability, team cooperation consciousness and leadership ability.

Objective To investigate the effects of exogenous hydrogen sulfide (H2S) on injury of rat hippocampus neurons induced by oxygen-glucose deprivation and restoration (OGD/R) and explore its mechanism.Methods Hippocampus neurons were isolated from embryonic day 16-18 (E16-18) rat embryos.Hippocampus was immediately removed and digested with 0.25％ trypsin.The neurons were isolated and cultured at 37 ℃ for 7 days and neuron-specific enolase (NSE) was detected by immunohistochemical staining method to identify neurons.At 8th day,the neurons were placed in deoxygenated glucose-free medium and exposed to 95％ N2-5％ CO2 in an air tight chamber for 1 hour,and then replaced the glucose-free medium with original medium,and returned the cultures to a standard incubator in 5％ CO2 at 37 ℃ and incubated for another 24 h.The neurons were divided into 3 groups:group Ⅰ control; group Ⅱ OGD/R,and group ⅢOGD + NaHS,the latter was further divided into 5 subgroups:groups Ⅲ1-5 with 25,50,100,200,400 μmol/L NaHS added,respectively.Then cell viability was quantified by MTT method,the level of lactate dehydrogenase (LDH) were detected,apoptosis was measured by Annexin V FITC/PI Apoptosis Kits,and RT-PCR was used to assay HIF-1 α mRNA in neurons in all groups.Results Compared with control group,the LDH level,apoptosis and expression of HIF-1α mRNA in group Ⅱ were significantly increased,the cell viability was significantly decreased (P ＜ 0.01).There were no significant differences in the LDH level,apoptosis and expression of HIF-1 α mRNA and the cell viability between group Ⅱ and group Ⅲ1 (P ＞ 0.05).Compared with group Ⅱ,the LDH level,apoptosis and expression of HIF-1α mRNA in group Ⅲ2-4 were significantly increased,the cell viability was significantly increased (P ＜ 0.01).Compared with group Ⅱ,the LDH level,apoptosis and expression of HIF-1 α mRNA in the group Ⅲ 5 were significantly decreased,the cell viability was significantly decreased (P ＜ 0.01).Conclusions H2S of low concentration has no significant effects on injury of rat hippocampus neurons induced by OGD/R.H2S of moderate doses can protect rat hippocampus neurons from OGD/R injury and H2S of high concentration can aggravate injury.The expression of HIF-1α mRNA in rat hippocampus neurons was increased after OGD/R,and the protective role of H2S is associated with increase in the expression of HIF-1α mRNA.

Objective To explore the effects of hydrogen sulfide (H2S) on apoptosis of cardiomyocytes after cardiopulmonary resuscitation (CPR) in rat models.Methods Forty-five male SD rats were randomly into sham group (n =15),CPR group (n =15) and NaHS group (n =15).Rats of CPR group and NaHS group were operated to induce cardiac arrest by transcutaneous electrical stimulation to epicardium.In NaHS group,NaHS (5 mg/kg) was administrated via the femoral venous line 1 min before CPR.Hemodynamic variables were monitored and obtained continuously.Survival rats were sacrificed at 24 h after restoration of spontaneous circulation and the hearts were removed for analysis by RT-PCR and TUNEL assays.Blood samples were collected and plasma content of cTnT was detected.Results Compared with the CPR group,animals treated with NaHS had improved left ventricular function (P ＜0.01),lower plasma cTnT levels (P ＜0.05) and decreased apoptosis index (P ＜ 0.01) 24 h after ROSC.The expressions of Caspase-3 mRNA,Bax mRNA and Bcl-2 mRNA in CPR group and NaHS group were higher compared with the control group (P ＜0.01).The NaHS group had lower expressions of Caspase-3 mRNA and Bax mRNA (P ＜0.01),but higher expression of Bcl-2 mRNA (P ＜0.05) compared with the CPR group.Conclusions Exogenous (H2S) regulated the expressions of Caspase-3,Bax and Bcl-2 mRNA,thereby preventing apoptosis of cardiomyocytes,inhibiting cTnT release and improving left ventricular function 24 h after CPR.

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.

Objective To study the efficacy of transurethral holmium laser resection as well as instant intravesical Pirarubicin instillation for superficial bladder carcinoma.Methods 51 cases with superficial bladder cancer were divided into observation group(A) including 26 cases and control group(B) including 25 cases stochastically.The 26 cases of group A were received transurethral holmium laser resection as well as instant intravesical Pirarubicin instillation therapy whereas 25 cases of group B received transurethral resection therapy.All patients of both groups were treated with intravesical instillation of Pirarubicin therapy regularly at least 1 year and have been followed up for 15 to 39 months.Results Differences were not significant between the two groups in the mean operation time and bladder perforation rate(P ＞0.05 ),but indwelling period of urethral catheter was markedly decreased in group A than group B ( P ＜ 0.05 ).There were 4 cases of recurrence in group A,recurrence rate was 15.4％ (4/26).While there were 11 cases of recurrence in group B,recurrence rate was 44.0％ (11/25 ).Significant difference in cancer recurrence rate was found between two groups ( P ＜ 0.05 ).Conclusion Compared with transurethral resection therapy transurethral holmium laser resection as well as instant intravesical Pirarubicin instillation for superficial bladder carcinoma was more effective and quicker recovery,which has a good applied future in the clinical practice.

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.

To investigate the interaction and involvement of sodium hydrosulfide (NaHS),a H2S 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 H2S formation) group.The four groups were observed at 3,6,9,12 h after treatment.We examined hippocampal H2S synthesis and the expression of cystathionine-β-synthetase (CBS),a major enzyme involved in the H2S 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,H2S 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 H2S can increase injurious effects and treatment with AOAA can protect the brain from injury.

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 determinate the effects of sodium tanshinone ⅡA sulfonate(STS)on cardiomyocyte hypertrophy and explore the relative effects of STS on mitogen-activated protein kinase signal transduction system in rats with cardiomyocyte hypertrophy through constricting the thoracic aorta.Methods The models of cardiomyocyte hypertrophy were established in vivo,and the thoracic aorta was partially tied between the right innominate and the left common carotid arteries.The rats were randomly divided into 6 groups(n=8/group)as follows:①sham,②transverse aortic constriction(TAC),③TAC+low-dose Tan(TAC+LT)(5 mg/kg),④TAC+middle-dose Tan(TAC+MT)(10 mg/kg),⑤TAC+high-dose Tan(TAC+HT)(20 mg/kg),and ⑥ TAC+Val(10 mg/kg).After treatment for 8 weeks,echocardiography was performed to observe the changes in hypertrophy and heart function,and heart samples were cut into transverse sections and stained with hematoxylin and eosin(H&E).The MAPKs protein expression in the cardiomyocytes was detected by Western blot.Results The heart weight index(HWI),left ventricular mass index(LVMI)and cross-sectional diameter of cardiomyocytes(CD),left ventricular posterior wall thickness(LVWT),and interventricular septal thickness(IVS)were significantly increased in TAC group as compared with sham group.The relative parameters in STS groups and Val group were reduced as compared with those in TAC group.Western blot analysis revealed the p-ERK and p-p38 expression was significantly decreased in TAC group as compared with sham group(P＜0.01).The p-ERK expression was significantly decreased in STS groups and Val group as compared with TAC group(P＜0.05).The TAC+HT group,TAC+MT group and Val group had significantly higher p-p38 expression than TAC group(P＜0.05).Conclusion Tanshinone ⅡA could regulate the expression of protein in MAPK pathway to exert its inhibitory effects on hypertrophy of cardiomyocytes.