Objective:To investigate the anticoagulant causes, hemorrhagic susceptibility factors and clinical characteristics of patients with warfarin-related major bleeding in the emergency department of a general hospital.Methods:In a registry study from January 2017 to February 2020, 114 cases of warfarin-related major bleeding patients admitted to Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University were enrolled. The descriptive methods were used to analyze anticoagulant causes, hemorrhagic susceptibility factors and clinical characteristics. Patients were divided into the international normalized ratio (INR) overrange group and the INR non-overrange group according to INR value during bleeding. The Chi-square test, Student’s t test, and Wilcoxon rank sum test were used to compare the differences between the INR overrange group and the INR non-overrange group. The Wilcoxon rank sum test and Student’s t test were used to analyze the characteristics of gastrointestinal tract bleeding and cerebral hemorrhage. Results:Warfarin-related major bleeding accounted for 0.36% (114/32 040) of first aid cases and 9.84% (114/1 158) of warfarin-taking cases, respectively. Seventy-seven cases (67.5%) of anticoagulant causes were related to atrial fibrillation (AF) and 32 cases (28.1%) were related to post-operative cardiac valve replacement. Of the bleeding susceptibility factors, HAS-BLED scored at 4.0 (3.0, 5.0), 84 cases (73.7%) had a history of drug use, 77 cases (67.5%) aged older than 65 years old, 65 cases (57.0%) had irregular INR monitoring, and 29 cases (25.4%) had recent increase in dose. Forty cases (35.1%) were gastrointestinal tract bleeding with the lowest hemoglobin (Hb) value and the highest score of HAS-BLED. Twenty-one cases (18.4%) were cerebral hemorrhage with the shortest prothrombin time (PT), the lowest INR value, the highest Hb, and the lowest score of HAS-BLED. Twelve cases (10.5%) died or gave up treatment in critical condition, including 6 cases of cerebral hemorrhage, 5 cases of gastrointestinal tract bleeding, and 1 case of hemoptysis. There were statistically significant differences in previous history of antiplatelet therapy, recent increase in dose, HAS-BLED score and bleeding site between the INR overrange group and the INR non-overrange group (all P<0.05). Conclusions:Among patients with warfarin-related major bleeding, AF and post-operative cardiac valve replacement are the main causes of warfarin anticoagulation. INR overrange is related to the previous history of antiplatelet therapy, recent increase in dose, and the high score of HAS-BLED. The gastrointestinal tract bleeding is the most common, with the lowest Hb value and the highest score of HAS-BLED. Cerebral hemorrhage is the second common, with the shortest PT, the lowest INR value, and the highest Hb. The incidence and mortality rates of warfarin-related major bleeding are relatively high.

Objective To assess the factors associated with the restoration of spontaneous circulation (ROSC) and 2-year survival prognosis in patients with cardiac arrest (CA) after acute myocardial infarction (AMI),and after ROSC,the effects of various factors on midian survival time and on 2-year survival.Methods In a registry study from January 2005 to January 2015,all consecutive AMI-induced CA patients treated with cardiopulmonary resuscitation (CPR) admitted to our hospital were enrolled.The survivors were followed-up for 2 years.Univariate analysis was applied to evaluate factors associated with rate of ROSC and 2-year survival.Multivariable logistic regression analysis was applied to evaluate statistically significant factors in the univariate analysis.Medians with inter-quartile ranges were used to describe 2-year survival time affected by various factors after ROSC.Kaplan-Meier survival curve analysis was used to evaluate the effect of factors on 2-year survival.Results A total of 254 cases with CA after AMI were enrolled,including 129 cases of ROSC and 71 cases of 2-year survival.Univariate analysis showed age ≥ 70 years,CA occurred during 22:00-8:00,the duration time ofCPR ≥ 15 min and adrenaline dosage ＞ 5 mg were unfavorable predictors of ROSC;while,left ventricular ejection fraction (LVEF) ≥ 40％ before CA,shockable rhythm and percutaneous coronary intervention (PCI) therapy were favorable predictors.Besides,age ≥ 70 years,intubation during CPR,adrenaline dosage ＞ 5 mg and cardiogenic shock were unfavorable predictors of 2-year survival;While,male,normal daily activity before CA and PCI treatment were favorable predictors.Multivariable analysis showed age,the duration of CPR,adrenaline dosage,LVEF before CA,the rhythm during CPR and PCI therapy were independent predictors of ROSC.Age and PCI therapy were independent predictors of 2-year survival.Among patients,the survival time was affected by various factors after ROSC,and the factors with minimum 25％ and small median value were associated with cardiac rupture,cancer,adrenaline dosage ＞ 5 mg and cardiogenic shock.The factor with maximum 25％ value was PCI treatment (216 days).Kaplan-Meier survival analysis suggested that age ≥ 70 years was an unfavorable factor of 2-years survival (Log-rank test,P=0.007);while,PCI treatment was a favorable factor (Log-rank test,P＜0.01).PCI-related prognosis analysis showed that the effectiveness of PCI was related to the timing of PCI,the number of infarctrelated artery and the difference in culprit lesion.Conclusions The age ≥ 70 years was disadvantageous to both ROSC and 2-year survival.PCI treatment was favorable to both ROSC and 2-year survival.

Objective To observe the expression changes in apoptosis-related microRNA(miRNA) in cerebral cortex after cardiac arrest-cardiopulmonary resuscitation(CA-CPR)in rats and explore the factors that may affect the mechanism of CPR. Methods 24 clean male Sprague-Dawley(SD)rats were randomly divided into three groups,the normal control group,sham operation group and CA-CPR group(each n=8). The animal model of CA induced by asphyxia was established and CPR was performed. In the normal control group,no special management was performed. In the sham operation group,only abdominal cavity anesthesia,tracheotomy,vascular puncture and electrocardiogram(ECG)were performed without clamping the trachea and resuscitating. Normal feeding in normal control group and 24 hours after tracheotomy in sham operation group,at 24 hours after recovery of spontaneous circulation(ROSC)in CA-CPR group,cerebral cortex specimens were obtained for detection of the expression of miRNA by using real time fluorescence quantitative reverse transcription - polymerase chain reaction(RT-PCR). Flow cytometry(FCM)was used to detect the neurocyte apoptotic rate. Results Compared between normal control and sham operation groups,there were no significant differences in the expression of apoptosis-related miRNA and neurocyte apoptosis rate of cerebral cortex(both P>0.05). Compared with sham operation group,in CA-CPR group, 16 miRNA expressions were up-regulated,including Let-7c,miR-15a,miR-21,miR-24,miR-29,miR-29b, miR-34a, miR-103, miR-200a, miR-200b, miR-200c, miR-210, miR-326, miR-338-3p, miR-494 and miR-497,and there were 22 down-regulated,being Let-7a,Let-7b,Let-7d,Let-7e,miR-19a,miR-19b-1, miR-20a,miR-20b,miR-23a,miR-23b,miR-25,miR-98,miR-107,miR-122a,miR-125a,miR-125b, miR-145,miR-181a,miR-181c,miR-335,miR-384-5p and miR-422a. Eight miRNA had significant changes at 24 hours after ROSC,in which miR-15a,miR-21,miR-34a,miR-497 were up-regulated respectively for 6.831±2.625,8.122±3.442,5.349±2.010,6.590±3.689 times,and miR-125b,miR-145,Let-7a,Let-7e were down-regulated respectively for 0.122±0.039,0.199±0.096,0.191±0.069,0.160±0.082 times. The apoptosis rate of cerebral cortex was increased significantly in CA-CPR group〔(32.23±5.31)%〕compared with that in normal control group〔(3.66±1.34)%〕and sham operation group〔(4.98±1.84)%,both P<0.01〕. Conclusions In early period after CA-CPR,obvious neurocyte apoptosis may be found in brain tissue of rats,and in the mean time, changes in apoptosis-related miRNA expression in cerebral cortex occur. The various types of miRNA with significant changes possibly play important roles in cerebral protection after CA-CPR in rats.
down-regulated respectively for 0.122±0.039,0.199±0.096,0.191±0.069,0.160±0.082 times. The apoptosis rate of cerebral cortex was increased significantly in CA-CPR group〔(32.23±5.31)%〕compared with that in normal control group〔(3.66±1.34)%〕and sham operation group〔(4.98±1.84)%,both P<0.01〕. Conclusions In early period after CA-CPR,obvious neurocyte apoptosis may be found in brain tissue of rats,and in the mean time, changes in apoptosis-related miRNA expression in cerebral cortex occur. The various types of miRNA with significant changes possibly play important roles in cerebral protection after CA-CPR in rats.

Objective To investigate the changes of serum gastrin level in patients with colon cancer and the relationship between serum gastrin level and colon cancer occurrence and development.Methods Data of 35 patients underwent colon cancer surgery from January 2010 to January 2012 in our hospital were collected,at the same time data of 28 patients with colonic polyps and 30 cases of normal were collected as normal control.Serum gastrin levels were tested by radioimmunoassay in patients with colon cancer before surgery,1,3,7 d after surgery and they were analyzed.Results The serum gastrin level of patients with colon cancer was significantly increased compared with colon polyps and healthy controls((92.45 ± 12.98) ng/L vs (49.66 ±10.34) ng/L vs (30.12 ±6.39) ng/L;F =9.455,P ＜0.001)).Serum gastrin level in patients with obstructive colon cancer was significantly higher than that in non-obstructive cancer((129.84 ± 15.32) ng/L vs (75.34 ±11.45) ng/L,t =12.181,P ＜0.001) ;Serum gastrin levels in patients who cut off colon tumor was signifcanfly lower than before surgery((43.02 ±8.34) ng/L,(40.74 ±6.78) rig/L,(38.12 ±7.09) ng/L vs (89.45 ±12.98) ng/L;P ＜0.05).But no significant change of serum gastrin levels in patients with the colon tumor compared with the preoperative((97.34 +8.30) ng/L vs (95.82 ±7.20) ng/L vs (94.44 ±7.74) ng/L vs (100.23 ± 10.82) ng/L; P ＞ 0.05).But there was significant difference on serum gastrin levels between patients who cut off colon tumor and patients with the colon tumor(within groups:F =8.341,P =0.012 ;between groups:F =7.871,P =0.024).Conchusion Serum gastrin levels in patients with colon cancer were significantly higher than that of patients with colon polyps and normal controls.There was also a significant reduction of serum gastrin in tumor resection,and therefore gastrin may be involved in the development of colon cancer.

Objective To study the effects of exogenous phosphocreatine (CP) on brain injury after cardiopulmonary resuscitation (CPR) in rats.Methods A total of 160 male adult SD rats were randomly ( random number) divided into 4 groups:sham-operation control group ( group A),CPR group ( group B),low-dose CP group ( group C),high-dose CP group ( group D),and each group was further divided into 5 subgroups (n =8) as per study at different intervals,0.5,3,6,12 and 24 h after restoration of spontaneous circulation (ROSC) in groups B,C and D or after tracheotomy in group A.Cardiac arrest (CA) was induced by using asphyxia to establish CPR model in group B,C and D.The CP0.5 g/kg used in group C or CP 1.0 g/kg used in group D was injected into femoral vein at beginning of ROSC.Rats in each subgroup were sacrificed and the tissues of frontal lobe of brain of rats were taken at different intervals.The levels of adenosine triphosphate (ATP),adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in cerebral cortex were measured by high performance liquid chromatography (HPLC),and values of total adenine nucleotides ( TAN ) and energy charge ( EC ) were detected.The activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase in cerebral cortex were assayed by spectrophotometric method. The pathological changes of cerebral cortex were observed under optical microscope.The experimental data were processed with analysis of variance by using SPSS 16.0 package. Results Compared with group A,the levels of ATP,TAN,EC,Na + -K + -ATPase,Ca2+ -Mg2+ -ATPase were lower ( P ＜ 0.05 or P ＜ 0.01 ) at each interval in groups B and C,and at intervals of 0.5,3,6,12 h in group D,and the levels of AMP were higher (P ＜ 0.01 ) at each interval in group B and at intervals of 0.5 h and 3 h in groups C and D.Compared with group B,the levels of ATP,TAN,EC,Na + -K + -ATPase,Ca2 + -Mg2+ -ATPase were higher ( P ＜ 0.05 or P ＜ 0.01 ),and the levels of AMP were lower ( P ＜ 0.05 or P ＜ 0.01 ) at intervals of 6,12 and 24 h in groups C and D.Compared with group C,the levels of ATP at interval of 24 h and TAN,Na +- K + -ATPase,Ca2 + -Mg2 + -ATPase at intervals of 6,12 and 24 h were higher in group D ( P ＜ 0.05 or P ＜ 0.01 ).There were severe pathological changes in cerebral cortex in group B,and mild changes in groups C and D. Conclusions There was obvious energy metabolism disorder after CPR in rats.Treatment with exogenous CP could increase the levels of ATP and activities of ATPase,alleviate pathological changes,especially in high-dose,and mitigate injury in cerebral cortex after CPR in rats.

Animal experiment is indispensable for biomedicine research,and contributes much to the development of biomedicine.With the development of society and advance of human civilization,the welfare of experimental animals and ethical issues of animal researches are drawing extensive attention.The current study investigated the application of experimental animals in the hospital researches,explored the relationship between animal experiment and ethics of animal welfare,and analysed the status of ethics of animal welfare.Further it discussed how to strengthen ethical review of animal experiment so as to promote the ethics management of hospital researches.

Objective To observe the changes of cell apoptosis and levels of Bcl-2 and Bax protein in myocardium after cardiopulmonary resuscitation (CPR) in rats and to study the protective effects of different doses of exogenous phosphocreatine (creatine phosphate, CP) on cell apoptosis. Methods A total of 32 male adult SD rats were randomly divided into 4 groups, namely control group ( group A), CPR group (group B), low dose CP group (group C, phosphocreatine 0. 5 g/kg given at beginning of CPR and 1.0 g/ kg 2 hour after CPR) and high dose CP group ( group D, phosphocreatine 1.0 g/kg at beginning of CPR and 2. 0 g/kg 2 hours after CPR) . Cardiac arrest was induced by asphyxiation and CPR was started 7 min after asphyxiation it groups B, C and D. Myocardium samples were taken 24 hours after CPR for detecting myocardium cell apoptosis by TUNEL method. The levels of Bcl-2 and Bax protein were measured by using immunohistochemistry. Experimental data were processed with variance analysis in SPSS package. Results Compared with group A, myocardium cell apoptosis index (AI), and the levels of Bcl-2 and Bax proteinincreased significantly in groups B, C and D (P ＜0. 01 ), and Bcl-2/Bax ratio decreased significantly (P ＜0. 01 ) . Compared with group B, myocardium cell AI and levels of Bcl-2 and Bax protein decreased significantly in groups C and D ( P ＜ 0. 01 ), and Bcl-2/Bax ratio increased significantly ( P ＜ 0. 01 ) .Compared with group C, myocardium cell AI and levels of Bcl-2 and Bax decreased significantly in group D (P ＜ 0. 05 ), and Bcl-2/Bax ratio increased significantly ( P ＜ 0. 05 ) . Conclusion Exogenous phosphocreatine, especially inlarge dose, could inhibit apoptosis of myocardium cells and alleviate myocardium injury after CPR in rats.

Objective To study the effect of Hemin on the level of neuroglobin (NGB) in cerebral cortex,neurodeficit score (NDS) and pathological changes in cerebral cortex after cardiopulmonary resuscitation (CPR) in rats. Method A total of 120 male Sprague Dawley(SD) rats were divided randomly into control group(A), CPR group(B) and Hemin group(C). The animal model of cardiac arrest (CA) induced by asphyxia was established and CPR was performed. The NGB level in cerebral cortex, NDS and pathological changes in cerebral cortex were examined 0.5 h,3 h,6 h, 12 h, 24 h after restoration of spontaneous circulation (ROSC) in each group. Experimental data were analyzed by using one-factor analysis of variance and Tukey test. Results In comparison with group A, the levels of NGB were significantly higher 12 h,and 24 h after ROSC (P ＜0.05 and P ＜0.01), the values of NDS were significantly lower at each interval after ROSC ( P ＜ 0.01 ) ,and the pathological changes were more severe at each interval after ROSC in group B. In comparison with group A, the levels of NGB were significantly higher 6 h, 12 h and 24 h after ROSC ( P ＜ 0.05 and P ＜ 0.01 ), and the values of NDS were significantly lower 3 h, 6 h, 12 h after ROSC ( P ＜ 0.01) in group C. In comparison with group B, the levels of NGB were significantly higher 12 h and 24 h after ROSC, the values of NDS were significantly higher 12 h and 24 h after ROSC, and the pathological changes were less in group C. Conclusions The NGB level increased in cerebral cortex, the NDS level decreased and severe pathological changes occurred in rats after CPR. The hemin treatment up-regulated the level of NGB, improved the NDS, mitigated pathological changes, alleviating the cerebral injury after CPR.

Objective To investigate the changes of serum and urine fluorion organic fluoride poisoning by inhaling, and to probe into the clinical application value of concentrations in different degrees and at different time in patients with acute evaluating the sertm and urine fluorion concentration in acute organic fluoride poisoning by inhaling. Method A study was carried out in 23 patients, who suffered from acute organic fluoride poisoning by inhaling and were admitted Zhejiang Quhua Hospital, from December 2000 to December 2008. According to the occupational acute organic fluoride poisoning diagnostic criteria(GBZ66-2002),23 patients were divided into mild poisoning group,moderate poisoning group and severe poisoning group. Serum and urine fluorion concentration of patients at 1,2,3,4,5 d after poisoning were measured by using Ion-Selective Electrodes. Fluorion concentration of 10 staffs of Fluorine chemical company was also measured at the same period as the control group. The values of serum and urine fluorion concentration were analyzed. Differences in serum and urine fluorion concentration between groups at different time points were compared by repeated measures ANOVA and variability were deemed as statistical significance when P ＜ 0.05. Results Compared with mild poisoning group, there was no statistically significant difference ( P ＞ 0.05) in serum and urine fluorion concentration at the same time point in 1 to 5 days after poisoning in moderate poisoning group, but there was statistically significant differences ( P ＜ 0.05 or P ＜0.01) in severe poisoning group. Compared with moderate poisoning group, there was statistically significant difference ( P ＜ 0.05) in serum and urine fluorion concentration at the same time point in 1 to 5 days after poisoning in severe poisoning group. Serum fluorion concentration in 1 to 5 days after poisoning in each poisoning groupswere statistically higher than those in control group ( P ＜ 0.05), but there was statistically significant elevation ( P＜ 0.05) in urine fluorion concentration only in 1 day in mild poisoning group, in 1 to 3 days in moderate poisoning groups, in 1 to 5 days in severe poisoning group. Conclusions Serum fluorion concentration can be used as the severity index of diagnosis and determine the extent in 5 days after acute organic fluoride poisoning by inhaling,and urine fluorion concentration can also be used as diagnostic indicators of intoxication, but only in earlier stage or severe poisoning.

Objective To investigate the serum concentration and expressions of S100β protein in hippocampus CA1 region and the changes of water content in rats with asphyxia following ulinastatin injection after cardiopul-monary resuscitation (CPR). Method One hundred twenty male adult SD rots were randomly divided into 3 groups:sham-operation group, CPR group and ulinastafin group. And each group was further divided into 5 sub-groups (n=8) based on various intervals, 0.5 h,3 h,6 h,12 h and 24 h after tracheotomy in sham-operation group or after ROSC in CPR group and ulinastatin group. Asphyxial cardiac arrest and CPR model of rat was used in CPR group and ulinastatin group in which bolus dose of 100 000 U/kg ulinastatin was injection into arteria carotis. Anaesthesia, tracheotomy and vascular canratlafion without asphyxia and CPR in sham-operation group. Samples from subgroups were taken at different intervals. Brain water content was measured by using wet-dry weight method. Serum S100β protein was measured with enzyme-linked immunosorbent assay ( ELISA). The expres-sion of S100β protein in hippocampus CA1 region was measured by using immunohistochemistry. Data were ana-lyzed by SPSS version 10.0 software. Results Compared with sham-operation group, the brain water content of rats elevated significantly in all CPR subgroups after ROSC (P<0.05 or P<0.01). The brain water content of rats decreased significantly 12 h and 24 h after ROSC in ulinastatin group in comparison with CPR group (P<0.05). The serum S100β protein started to elevated significantly 0.5 h after ROSC in CPR group, and reached the peak 12 h after ROSC (P<0.01).serum S100β decreased 6 h,12 h and 24 h after ROSC in ulinastatin group compared with CPR group (P<0.01).The expression of S100β protein in hippocampus CA1 region remained at a low level in sham-operation group. The expression of S100β protein elevated significantly in all CPR subgroups after ROSC compared with sham-operation group (P<0.05 or P<0.01). Compared with CPR group, the ex-pression of S100β protein decreased after ROSC in ulinastatin group(P<0.05) .However,the expression of S100β protein in hippocampus CA1 region was significantly correlative with brain edema in all subgroups of CPR (r=0.862, P<0.05). Conclusions Ulinastatin can decrease serum S100β protein and the expression of S100β pro-tein in hippocampus CA1 region and lessen the severity of cerebral edema, alleviate the brain isehemic injury in rats after cardiopulmonary resuscitation.