Objective To investigate the effects of butorphanol pretreatment on myocardial injury induced by limb ischemia/reperfusion.Methods Forty patients with distal lower extremity orthopedic surgery (ASA Ⅰ or Ⅱ) were divided into two groups by random digits table method with 20 cases each:butorphanol group and control group.Epidural anesthesia was selected in all patients.In butorphanol group,patients were given butorphanol 0.04 mg/kg intravenously 15 min before tourniquet.In control group,equal volume of normal saline was infused at the same time.Blood samples were taken from jugular vein before tourniquet (T0),then 5 min(T1),2 h (T2),6 h (T3),12 h (T4) and 24 h (T5) after the second reperfusion of tourniquet.The serum creatine kinase isoenzyme MB (CK-MB),cardiac troponin Ⅰ (cTnI),tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels were determined.Results Compared with those at T0,the serum C K-MB levels were increased at T2-T5,the serum cTnI,MDA,TNF-α levels were increased at T1-T5 in control group,and there were significant differences (P ＜ 0.05).Compared with those at T0,the serum CK-MB levels were increased at T3,T4,the serum TNF-α levels were increased at T1-T3,the serum cTnI levels were increased at T1-T5 in butorphanol group,and there were significant differences (P ＜ 0.05).Compared with those in control group,the serum CK-MB levels were decreased at T2-T5 [(20.2 ± 5.0) U/L vs.(35.3 ±6.8) U/L,(32.3 ±3.7) U/L vs.(48.6 ±8.5) U/L,(29.5 ±5.4) U/L vs.(51.5 ±8.0) U/L,(22.2 ±4.8) U/L vs.(33.7 ±6.7) U/L],the serum cTnI,TNF-α levels were decreased at T1-T5 [(0.158 ± 0.016) μg/L vs.(0.278 ±0.021) μg/L,(0.169 ±0.036) μg/L vs.(0.332 ± 0.062) μg/L,(0.357 ±0.049) μg/L vs.(0.623 ±0.083) μg/L,(0.178 ±0.045) μg/L vs.(0.383 ±0.059) μg/L,(0.138 ±0.016) μg/L vs.(0.263 ±0.023) μg/L; (1.63 ±0.13) μg/L vs.(2.12 ±0.08) μg/L,(1.69 ± 0.08) μ g/L vs.(2.28 ± 0.09) μ g/L,(1.63 ± 0.09) μ g/L vs.(2.25 ± 0.07) μ g/L,(1.23 ± 0.14) μμg/Lvs.(1.93±0.12) μg/L,(1.13±0.15) μμg/Lvs.(1.79±0.07) μμg/L],theserumMDAlevelswere decreased at T1-T4 [(4.82 ±0.53) nmol/L vs.(6.68 ±0.67) nmol/L,(4.99 ±0.61) nmol/L vs.(7.59 ±0.72) nmol/L,(5.02 ±0.43) nmol/L vs.(7.54 ±0.63) nmol/L,(4.52 ±0.55) nmol/L vs.(6.52 ±0.47) nmol/L] in butorphanol group,and there were significant differences (P ＜0.05).Conclusion Butorphanol pretreatment can improve the serum CK-MB,cTnI levels,and has a protective role for myocardial injury induced by limb ischemia/reperfusion.

Objective To evaluate the effects of butorphanol pretreatment on myocardial damage induced by limb ischemia/reperfusion (I/R) in rats.Methods One hundred and eight male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups (n =36 each) using a random number table:sham operation group (group S),I/R group and butorphanol pretreatment group (group B).Limb ischemia was induced by occlusion of bilateral hind limbs for 2 h followed by reperfusion in I/R and B groups.At 10 min before ischemia,butorphanol 0.2 mg/kg was injected via the right jugular vein in group B,while the equal volume of normal saline was injected in group I/R.Six rats were chosen randomly before ischemia (baseline,T0) and at 2,6,12,24 and 48 h after reperfusion (T1-5) and blood samples were taken from the abdominal aorta for determination of the serum creatine kinase isoenzyme-MB (CK-MB) activity and cardiac troponin Ⅰ (cTnI) concentration.The animals were then sacrificed and myocardial specimens were obtained for determination of myocardial apoptosis (using TUNEL) and the expression of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) (using Western blot analysis).Apoptosis index was calculated.Results Compared with group S,the serum CK-MB and cTnI levels were significantly increased at T1-5,and the apoptosis index and expression of JNK and ERK were increased at T2-5 in group I/R (P ＜ 0.05).Compared with group I/R,the pathological changes of myocardium were significantly reduced at T4,the serum CK-MB and cTnI levels were decreased at T2-5,the apoptosis index was decreased at T4,5,the expression of ERK was up-regulated at T2-5,and the expression of JNK was down-regulated at T2-4 (P ＜ 0.05).Conclusion Butorphanol pretreatment can reduce apoptosis in myocardial cells through activating MAPK signal transduction pathway,up-regulating ERK expression and down-regulating JNK expression,thus attenuating myocardial damage induced by limb I/R in rats.

The blood-brain barrier (BBB) is a semi-permeable biological barrier between brain tissue and plasma, however, its physical, enzymatic and immune properties, as well as its unique transport mechanism severely limit the entry of therapeutic drugs and diagnostic agents into the brain, which poses great challenges for the prevention and treatment of brain diseases. Hence, this review summarizes and discusses the complex structural components and various transport mechanisms of BBB, and interprets the difficulties and feasible ways of drug delivery across BBB. Furthermore, the latest research progress and future development trends of various delivery systems for brain drug delivery are introduced and discussed to provide references for further perfecting their design and driving their transformation. Finally, this review discusses the pathological changes of BBB in brain diseases and the design of drug delivery strategies for pathological BBB. Collectively, this review highlights the design and optimization of drug delivery strategies across the BBB based on nano-delivery system and provides accessible guide for current opportunities and challenges of intracerebral drug delivery.

Objective: To analyze the occurrence features of adverse events following immunization (AEFI) of Seasonal Influenza Vaccines (InfV) used in China, 2015-2018 influenza season. Methods: InfV (including concurrent administered with other vaccines) AEFI data were collected through the Chinese national AEFI information system during 2015.9.1-2018.8.31 (excluding Chinese Hong Kong, Macao and Taiwan data). The vaccine lot release data were collected from National Institutes for Food and Drug Control published database. Time periods of three influenza season were 2015.9.1-2016.8.31, 2016.9.1-2017.8.31, 2017.9.1-2018.8.31. The vaccines used and included in this analysis were trivalent inactivated influenza vaccine (IIV3)-Split, IIV3-Split (Children) and IIV-subnit. The incidence of AEFI were calculated (per 100 000 release doses), and epidemiological characteristic were analyzed using descriptive methodology. Results: A total of 8 464 InfV AEFIs were collected in 2015-2018 influenza season from National AEFI Information System, in which 5 646 were IIV3-split, with the rate of 10.64/100 000 release doses, 2 818 were IIV3-split (Children), with the rate of 9.355/100 000 release doses. The most common symptom was fever (axillary temperature ≥37.1 ℃) within vaccine reactions, with a number of 6 207 cases. In which, there were 3 554 cases with fever (axillary temperature ≥38.6 ℃) and the estimated reporting rate was 4.274/100 000 release doses. In all rare vaccine reactions, the most common diagnosis was anaphylactic rash(442, 0.531/100 000 release doses) and angioedema (70, 0.084/100 000 release doses). Even the rates of serious rare vaccine reactions were low, febrile Convulsion (27, 0.032/100 000 release doses) and Henoch-Schönlein Purpura(HSP) (21, 0.025/100 000 release doses) were relatively common in serious rare vaccine reactions during the study period. Conclusion The estimated rate of rare vaccine reactions related toInfV was relatively low. In all vaccine reactions, fever was the most common symptoms. The most common diagnosis of non-serious rare vaccine reaction were anaphylactic rash and angioedema. The incidence of serious rare vaccine reactions was low.

Objective To comprehensively evaluate the clinical efficacy of hemoperfusion (HP) combined with continuous veno-venous hemofiltration (CVVH) on acute paraquat poisoning (APP).Methods Literatures of Chinese and English randomized controlled trials (RCTs), case control and cohort study on HP combined with CVVH in the treatment of APP from the PubMed, Embase, Wanfang, and CNKI up to November 2017 were enrolled (the subjects were > 16 years old). The obtained literatures were strictly screened and evaluated in quality, and data such as mortality, the life time of dead patients, inefficiency rate, incidence of multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) were extracted. Meta-analysis was performed by RevMan 5.3. Results Twenty-one studies were included with 2222 subjects, among whom 976 subjects were in HP combined with CVVH group (experimental group) and 1246 subjects in HP group (control group). Compared with control group, the mortality in experimental group were significantly decreased [43.77％ (362/827) vs. 55.26％ (604/1093), odds ratio (OR) =0.68, 95％ confidential interval (95％CI) = 0.56-0.82,P = 0.0001], the life time of death patients was significantly prolonged [mean difference (MD) = 4.63, 95％CI = 2.60-6.66,P < 0.00001], incidence of MODS [25.93％ (70/270) vs. 55.36％ (155/280),OR = 0.26, 95％CI = 0.14-0.49,P< 0.0001], and incidence of ARDS [30.37％ (82/270) vs. 51.07％(143/280),OR = 0.42, 95％CI = 0.30-0.61,P < 0.00001], and inefficiency rate [8.72％ (13/149) vs. 34.64％ (53/153),OR=0.17, 95％CI = 0.09-0.34, P < 0.00001] were significantly reduced. Funnel chart showed that except the publication bias of mortality rate, there were less publication bias about other indicators among studies.Conclusion HP combined with CVVH can significantly reduce the mortality of patients with APP compared with HP alone on the whole, prolong the life time and reduce the occurrence of MODS and ARDS, thus improving the treatment efficiency.

Objective To investigate the effect of extracorporeal membrane oxygenation (ECMO) on critical patients with non-pulmonary primary disease in the emergency department. Methods The literature of English and Chinese clinical studies on the ECMO treating critical patients with non-pulmonary primary disease published before August 2017 were electronically searched on PubMed, Embase and other databases. The obtained articles were selected, their qualities were strictly evaluated, and the in-hospital survival rate, 3-month, 6-month and 1-year survival rate, as well as the average intensive care unit (ICU) and length of hospital stay were extracted. This meta-analysis were performed using RevMan software (Version 5.0, Cochrane collaboration). Results A total of 11 articles (n=3043) were enrolled including 616 cases of ECMO treatment group and 2427 cases of control group. Fitting results showed that compared with the traditional treatment, application of ECMO can improve the in-hospital survival rate[52.1％(321/616) vs. 32.1％ (780/2427); OR=2.02; 95％CI:1.11-3.67, P=0.02] and the survival rate more than 90 days[42.1％ (61/145) vs. 17.1％ (38/222); OR=3.98; 95％CI:2.30-6.89, P<0.01];and prolong the average length of hospital stay (MD=-5.35, 95％CI:-8.10--2.60, P<0.01) and ICU time(MD=-8.99, 95％CI:-8.20--1.80, P<0.01). Conclusions Meta-analysis of existing studies showed that application of ECMO can improve the short-term and long-term prognosis of critical patients with non-pulmonary primary disease. However, due to the small number of studies and the large heterogeneity of the study population, it is necessary to carry out more, large samples and high quality randomized controlled clinical trials.

Objective To observe the effects of dopamine in different doses on hemodynamics and cerebral oxygen metabolism in the early stage of post-resuscitation in rabbit with cardiac arrest.Methods Healthy adult rabbits were randomly(random number) divided into 4 groups according to the different doses of dopamine administration:control group (CG),low dose group (LG),medium dose group (MG),high dose group (HG),(n=15 in each group).Ventricular fibrillation (VF) was induced by electricity and cardiopulmonary resuscitation (CPR) was performed subsequently as the experiment designed.When 10 rabbits with restoration of spontaneous circulation (ROSC) were got each group,it was enough for experiment carried out.Cardiac output (CO),mean arterial pressure (MAP),heart rate (HR),systemic vascular resistance index (SVRI) and the cerebral local tissue blood oxygen saturation (TOI) were observed at 0 min,15 min,30 min,60 min,120 min after ROSC.The animals were sacrificed at 120 min after ROSC,brain tissues were harvested for study by using HE staining.Repeated measure analysis of variance was used to determine the statistical significance among the four groups at different intervals.Multi-group quantitative data was analyzed by one way ANOVA and then further by LSD test for multiple comparisons.Chi-square test or Fisher's exact probabilities was applied for multi-group binomial classification variable.Log-rank test was used for comparisons of survival curves in four groups.A twotailed value of P＜0.05 was considered statistically significant.Results There were no differences in the rate of ROSC among groups.Compared with CG and LG,ROSC time was shorter in MG (277±15 vs.190±12,P＜0.01;252±16 vs.190±12,P=0.016) with higher 120 min survival rate (20％ vs.90％,x2=9.899,P=0.005;30％ vs.90％,x2=7.5,P=0.02).CO was higher in MG than that in other groups at all given intervals in the early stage of post-resuscitation(P＜0.05).MAP levels were significantly higher in MG and HG compared with CG and LG at given intervals 15 min after ROSC (P＜0.05).SVRI was significantly higher in HG than that in other groups at all given intervals after ROSC (P＜0.05).Compared with other groups,the TOI levels in MG were significantly higher than that in other groups at 15 min and 30 min after ROSC (P＜0.05).The median survival time in MG and HG was significantly longer than that in CG and LG.The number of cellular necrosis in MG (28.4±1.0) was significantly fewer than that in other groups (CG 41.2±1.5;LG 41.0±2.0;HG 39.6±1.9) (P＜0.01).Conclusion The moderate dose of dopamine might maintain MAP and CO at a higher level meeting the cerebral oxygen metabolism in the early stage of post-resuscitation from cardiac arrest in rabbits.