Effects of Chinese Medicine Shen-Fu Injection(参附注射液)on the Expression of Inflammatory Cytokines and Complements during Post-Resuscitation Immune Dysfunction in A Porcine Model

Objective:To investigate the action of Shen-Fu Injection(参附注射液,SFI) in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest(CA) and resuscitation.Methods:Thirty pigs were randomly divided into the sham(n=6) and 3 returns of spontaneous circulation(ROSC) groups(n=24).After 8-min untreated ventricular fibrillation and 2-min basic life support,24 pigs of the ROSC groups were randomized into three groups(n=8 per group),which received central venous injection of SFI(SFI group),epinephrine(EP group),or saline(SA group).Hemodynamic status and blood samples were obtained at 0,0.5,1,2,4,6,12,and 24 h after ROSC.Results:Serum concentrations of specific activation markers of the complement system C3,C4 and C5b-9 were increased during cardiopulmonary resuscitation th rough1 24 h after ROSC.There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA.Compared with the EP and SA groups,SFI treatment reduced the proinflammatory cytokines levels of interleukin(IL)-6,IL-8and tumor necrosis factor α(TNF-α,P0.05),and increased the anti-inflammatory cytokine levels of IL-4 and IL-10(P0.05).Further,SFI treatment decreased the values of C3,C4 and C5b-9 compared with the EP and SA groups.Conclusions:SFI,derived from the ancient Chinese medicine,has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels.The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.     

Comparison of epinephrine and Shen-Fu injection on resuscitation outcomes in a porcine model of prolonged cardiac arrest

Background Epinephrine has been used as a first-choice vasopressor drug for cardiac arrest （CA） since 1974.However,the administration of epinephrine is controversial.This study aims to compare the effects of Shen-Fu injection （SFI） and epinephrine on resuscitation outcomes in a porcine model of prolonged CA.Methods Ventricular fibrillation （VF） was electrically induced.After 8 minutes of untreated VF and 2 minutes of chest compressions,24 pigs were randomly divided into 3 groups （n=8 per group）：central venous injection of SFI （SFI group）,epinephrine （EPI group）,or saline solution （SA group）.The haemodynamic status and oxygen metabolism parameters,including cardiac output,mean arterial pressure,left ventricular dp/dtmax and negative dp/dtmax,oxygen delivery （DO2）,and oxygen consumption （VO2）,were calculated.Results SFI shortened the time to restoration of spontaneous circulation （ROSC） and decreased the number of shocks,similar to epinephrine.However,the mean arterial pressure,cardiac output,left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the EPI group at 4 and 6 hours after ROSC.VO2 and ERO2 decreased after ROSC and then increased.VO2 and ERO2 were significantly higher in the SFI group than in the EPI and SA groups after ROSC,while those were lowest in the EPI group among all groups.Conclusions SFI shortened the time to ROSC and decreased the number of shocks,similar to epinephrine.However,SFI improved oxygen metabolism,and produced a better hemodynamic status compared with epinephrine.SFI might be a potentially vasopressor drug for the treatment of CA.     

Effects of Shenfu Injection (参附注射液) on Cerebral Metabolism in A Porcine Model of Cardiac Arrest

Objective:To investigate the effects of Shenfu Injection(参附注射液,SFI) on cerebral metabolism in a porcine model of cardiac arrest(CA).Methods:Thirty Wuzhishan minipigs were randomly assigned to the control group(n=6),epinephrine group(EP group,n=12) and SFI group(n=12).After8 min of untreated ventricular fibrillation(VF),pigs in the EP group or SFI group were administered with either EP(0.02 mg/kg) or SFI(1.0 mL/kg),respectively.After successful resuscitation,cerebrospinal fluid(CSF) levels of glucose,pyruvate,lactate,glutamate and glycerol were measured at 1,6,12 and 24 h after recover from spontaneous circulation(ROSC).In addition,neurologic deficit score(NDS) was calculated at 24 h after ROSC.Surviving pigs were killed at 24 h after ROSC,and the brain tissue was obtained for ultra-microstructure examination.Results:Compared with the EP group,CSF glucose and pyruvate levels were higher(all P0.01),and lactate levels were lower in the SFI group(P0.01).Meanwhile,CSF glutamate and glycerol levels in the SFI group were lower in comparison to the EP group(all P0.05).In addition,SFI decreased NDS at 24 h after ROSC(P0.01),and alleviated the histopathological damage of the brain.Conclusions:SFI could alleviate brain injury after CA,which may be associated with improving cerebral metabolism.     

Shen-Fu Injection(参附注射液) Alleviates Post-resuscitation Myocardial Dysfunction by Up-regulating Expression of Sarcoplasmic Reticulum Ca2~+ -ATPase

Objective: To compare the effect of Shen-Fu Injection(SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca2~+ ATPase 2a(SERCA2a) in a pig model with post-resuscitation myocardial dysfunction. Methods: Ventricular fibrillation(VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation(CPR), all animals were randomly administered a bolus injection of saline placebo(SA group, n=10), SFI(0.8 mg/kg, SFI group, n=10) or epinephrine(20 μg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation(ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase(AC), cyclic adenosine monophosphate(c AMP) and the expressions of β1-adrenoceptor(AR) and SERCA 2a were determined. Results: Cardiac output, left ventricular dp/dt_(max) and negative dp/dt_(max) were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of β1-AR and SERCA2 a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups(P0.05 or P0.01). Conclusions: The administration of epinephrine during CPR decreased the expression of SERCA2 a and aggravated postresuscitation myocardial function(P0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2 a expression.     

Comparison of Shenfu Injection(参附注射液) and Epinephrine on Catecholamine Levels in A Porcine Model of Prolonged Cardiac Arrest

Objective:To compare the effects of Shenfu Injection(SFI) and epinephrine(EPI) on catecholamine levels in a porcine model of prolonged cardiac arrest(CA).Methods:After 8 min of untreated ventricular fibrillation,24 Wuzhishan miniature pigs were randomly assigned to one of the three groups(n=8 per group) and received central venous injection,respectively:SFI group(1 mL/kg),EPI group(20 μg/kg EPI),and normal saline(NS) group.Cardiac output(CO),maximum rate of increase/decrease in left ventricular pressure(±dp/dt),serum levels of EPI,norepinephrine(NE),and dopamine(DA) were determined at baseline and at 0.5,1,2,and 4 h after restoration of spontaneous circulation.Results:The duration of cardiopulmonary resuscitation was shorter in the EPI and SFI groups than in the NS group(P0.05).The EPI level increased significantly after restoration of spontaneous circulation(ROSC) in all three groups,and was significantly different between the EPI group and the other two groups immediately after ROSC(both P0.01),but these differences gradually disappeared over time.There were no significant differences in NE or DA levels among the three groups,and there were no correlations between catecholamine levels and CO or dp/dt(P0.05).Conclusions:SFI did not significantly affect endogenous catecholamine levels during cardiopulmonary resuscitation after prolonged ventricular fibrillation.However,SFI improved oxygen metabolism,and produced a better hemodynamic status compared with EPI.SFI might be a potentially vasopressor drug for the treatment of CA.     

Protective Effect of Shenfu Injection on Vascular Endothelial Damage in a Porcine Model of Hemorrhagic Shock

Objective:To investigate the effects of Shenfu Injection(SFI) on endothelial damage in a porcine model of hemorrhagic shock(HS).Methods:After being bled to a mean arterial pressure of40±3 mm Hg and held for 60 min,32 pigs were treated with a venous injection of either shed blood(transfusion group),shed blood and saline(saline group),shed blood and SFI(SEI group) or without resuscitation(sham group).Venous blood samples were collected and analyzed at baseline and 0,1,2,4,and 6 h after HS.Tumor ne...     

Effect of different resuscitation strategies on post-resuscitation brain damage in a porcine model of prolonged cardiac arrest

Background The choice of a defibrillation or a cardiopulmonary resuscitation （CPR）-first strategy in the treatment of prolonged cardiac arrest （CA） is still controversial. The purpose of this study was to compare the effects of defibrillation or CPR administered first on neurological prognostic markers in a porcine model of prolonged CA. Methods After 8 minutes of untreated ventricular fibrillation （VF）, 24 inbred Chinese Wuzhishan minipigs were randomized to receive either defibrillation first （ID group, n=12） or chest compression first （IC group, n=12）. In the ID group, a shock was delivered immediately. If defibrillation failed to attain restoration of spontaneous circulation （ROSC）, manual chest compressions were rapidly initiated at a rate of 100 compressions/min and a compression-to-ventilation ratio of 30：2. If VF persisted after five cycles of CPR, a second defibrillation attempt was made. In the IC group, chest compressions were delivered first, followed by a shock. After successful ROSC, hemodynamic status and blood samples were obtained at 0.5, 1, 2, 4, 6, and 24 hours after ROSC. Porcine-specific neuron-specific enolase （NSE） and S100B were measured from sera using enzyme-linked immunosorbent assays. Porcine cerebral performance category scores were used to evaluate preliminary neurological function following 24 hours recovery. Surviving pigs were sacrificed at 24 hours after ROSC and brains were removed for electron microscopy analysis. Results The number of shocks, total defibrillation energy, and time to ROSC were significantly lower in the ID group compared with the IC group. Compared with the IC group, S100B expression was decreased at 2 and 4 hours after ROSC, and NSE expression decreased at 6 and 24 hours after ROSC in the ID group. Brain tissue analysis showed that injury was attenuated in the ID group compared with the IC group. There were no significant differences between 6 and 24 hours survival rates. Conclusion Defibrillation first may result in a shorter tim     

Effects of matrix metalloproteinase 9 inhibition on the blood brain barrier and inflammation in rats following cardiopulmonary resuscitation

Background Neuroprotective strategies following cardiopulmonary resuscitation （CPR） are an important focus in emergency and critical care medicine. Matrix metalloproteinases （MMPs）, especially MMP9 attracted much attention because of its function in focal brain ischemia/reperfusion injury. In the focal cerebral ischemia model in rats, SB-3CT can suppress the expression of MMP9, relieving brain edema, and there was no studies on global cerebral ischemiareperfusion injury after CPR. Methods One hundred and twenty rats were randomly assigned to sham-operated （n=40）, resuscitation treatment （n=40）, and resuscitation control （n= 40） groups. Sham-operated group rats were anesthetized only and intubated tracheally, while the resuscitation treatment and resuscitation control groups also received cardiac arrest by asphyxiation, In the resuscitation treatment group, SB-3CT was injected intraperitoneally after restoring spontaneous circulation （ROSC）, defined as restoration of supraventricular rhythm and mean arterial pressure （MAP） 〉 60 mm Hg for more than 5 minutes. The resuscitation control group also implemented ROSC without injection of SB-3CT. The rats were executed and samples were taken immediately after death, then at 3, 9, 24, and 48 hours （n=-8）. Brain tissue expression of MMP9 protein, MMP9 mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 was measured, and the brain tissue ultramicrostructure studied with electron microscopy. Results In the resuscitation control group, brain tissue expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 were significantly elevated at 3 hours, and peaked at 24 hours after resuscitation, when compared with the sham-operated group （P 〈0.05）. 1issue ultramicrostructure also changed in the resuscitation control group. By contrast, although all these indexes were increased in the resuscitation treatment group compared with the sham-operated group （P 〈0.05）, they were lower than in the resuscitation control group （P 〈0.05）. Conclusions Expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 increased in rat brain tissue after CPR, indicating disruption of the blood-brain barrier and excess inflammatory reaction. MMP9 expression was reduced with SB-3CT, resulting in reduced brain injury.     

Application of Positron Emission TomographyintheDetection of Myocardial Metabolism inPigVentricularFibrillation and Asphyxiation Cardiac Arrest ModelsafterResuscitation

Objective To study the application of positron emission tomography （PET） in detection of myocardia metabolism in pig ventricular fibrillation and asphyxiation cardiac arrest models after resuscitation. Methods Thirty-two healthy miniature pigs were randomized into a ventricular fibrillation cardiac arrest （VFCA） group （n=16） and an asphyxiation cardiac arrest （ACA） group （n=16）. Cardiac arrest （CA） was induced by programmed electric stimulation or endotracheal tube clamping followed by cardiopulmonary resuscitation （CPR） and defibrillation. At four hours and 24 h after spontaneous circulation was achieved, myocardial metabolism was assessed by PET. 18F-FDG myocardial uptake in PET was analyzed and the maximum standardized uptake value （SUVmax） was measured. Results Spontaneous circulation was 200% and 62.5% in VFCA group and ACA group, respectively. PET demonstrated that the myocardial metabolism injuries was more severe and widespread after ACA than after VFCA. The SUVrnax was higher in VFCA group than in ACA group （P〈0.01）. In VFCA group, SUVmax at 24 h after spontaneous circulation increased to the level of baseline. Conclusion ACA causes more severe cardiac metabol associated with less successful resuscitation. Myocardial sm injuries than VFCA. Myocardial dysfunction is stunning does occur with VFCA but not with ACA.     

Distinct properties and metabolic mechanisms of postresuscitation myocardial injuries in ventricular fibrillation cardiac arrest versus asphyxiation cardiac arrest in a porcine model

Background The two most prevalent causes of sudden cardiac death are ventricular fibrillation cardiac arrest （VFCA） and asphyxiation cardiac arrest （ACA）. Profound postresuscitation myocardial dysfunction has been demonstrated in both VFCA and ACA animal models. Our study aimed to characterize the two porcine models of cardiac arrest and postresuscitation myocardial metabolism dysfunction. Methods Thirty-two pigs were randomized into two groups. The VFCA group （n=16） were subject to programmed electrical stimulation and the ACA group （n=16） underwent endotracheal tube clamping to induce cardiac arrest （CA）. Once induced, CA remained untreated for a period of 8 minutes. Two minutes following initiation of cardiopulmonary resuscitation （CPR）, defibrillation was attempted until return of spontaneous circulation （ROSC） was achieved or animals died. To assess myocardial metabolism, 18F-FluoroDeoxyGlucose Positron Emission Tomography was performed at baseline and 4 hours after ROSC. Results ROSC was 100% successful in VFCA and 50% successful in ACA. VFCA had better mean arterial pressure and cardiac output after ROSC than ACA. Arterial blood gas analysis indicated more detrimental metabolic disturbances in ACA compared with VFCA after ROSC （ROSC 0.5 hours, pH： 7.01±0.06 vs. 7.21±0.03, P〈0.01; HCO3： （15.83±2.31 vs. 20.11±1.83） mmol/L, P〈0.01; lactate： （16.22±1.76 vs. 5.84±1.44） mmol/L, P〈0.01）. Myocardial metabolism imaging using Positron Emission Tomography demonstrated that myocardial injuries after ACA were more severe and widespread than after VFCA at 4 hours after ROSC （the maximum standardized uptake value of the whole left ventricular： 1.00±0.17 vs. 1.93±0.27, P〈0.01）. Lower contents of myocardial energy metabolism enzymes （Na＊-K＊-ATPase enzyme activity, Ca2＊- ATPase enzyme activity, superoxide dismutase and phosphodiesterase） were found in ACA relative to VFCA. Conclusions Compared with VFCA, ACA causes more severe myocardium injury an     

Role of Shenfu Injection (参附注射液) in rats with systemic inflammatory response syndrome

Objective： To investigate the role of Shenfu Injection （参附注射液, SFI） in rats with systemic inflammatory response syndrome （SIRS）. Methods： The SIRS rat model was induced by the intravenous injection of lipopolysaccharide （LPS）. Forty-five male Wistar rats were randomly divided into 3 groups, the sham operative control group （control group, n=5）, the SIRS model group （model group, n=20） and the SFI treatment group （SFI group, n=20）. LPS was injected through the external jugular vein （12 mg/kg, 6 mg/mL） to all rats except for those in the control group, and SFI （10 mL/kg） was given to those in the SF group only once through intraperitoneal injection, while the normal saline （10 mL/kg） was given to those in the model group. For those in the control group, normal saline was given through the external jugular vein （2 mL/kg） and intraperitoneal injection （10 mL/kg）. Then, rats in the model group and SFI group were divided into 4 subgroups according to the time points, i.e., 1 h, 2 h, 4 h and 6 h subgroups, 5 rats in each group. The activity of nuclear factor of κB （NF-κB） of in blood mononuclear cells and the plasma levels of tumor necrosis factor- α （TNF- α ） and interleukin 6-（IL-6） were determined using enzyme-linked immunoabsordent assay （ELISA） at 1 h, 2 h, 4 h and 6 h after modeling. Histopathologic changes of the lung and liver were observed under a light microscope. Results： Compared with the control group, the activity of NF-κB in mononuclear cells and the plasma level of TNF-α were obviously increased at each time points （all P〈0.01）, reaching the peaks at 2 h after modeling. The plasma level of IL-6 increased gradually as time went by in the model group （P〈0.01）. Pathological examination showed pulmonary alveoli hemorrhage, edema and inflammatory cell infiltration in the lung tissue, and angiotelectasis, congestion, and local necrosis in the liver tissue in the model group. Compared with the model group, the activity     

Effect of Shen-Fu Injection(参附注射液)on Hemodynamics in Early Volume Resuscitation Treated Septic Shock Patients

Objective: To investigate the hemodynamic effect of Shen-Fu Injection(参附注射液, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output(PICCO). Methods: All septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1 st, 2014 to December 31 th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group(33 cases) and control group(32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation. Results: The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h(P0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group(P0.05), including cardiac index(CI), global end diastolic volume index(GEDI), mean arterial pressure(MAP) and heart rate(HR). In addition, there was no significant change of extra-vascular lung water index between the two groups(P0.05). Conclusion: SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients.     

Relief of abdominal pain by morphine without altering physical signs in acute appendicitis

Background Abdominal pain is a common symptom among patients with acute appendicitis, yet these patients have long been denied relief from suffering because of widespread misconceptions associated with the use of opioids. We determined whether morphine hydrochloride masked the physical signs in adults with acute appendicitis and assessed the efficacy of morphine in relieving abdominal pain. Methods A prospective, double-blind, placebo controlled, clinical trial was conducted with 106 adult patients between 16 and 70 years old with acute appendicitis. Patients were randomly divided into a morphine group （n=-54） or a normal saline group （n=52）. All patients presented with acute abdominal pain with onset within 3 days. The morphine group received hypodermic injection of morphine （0.15 mg/kg; maximum 20 mg） and the control group members were given an equivalent volume of normal saline solution. The clinical symptoms, physical signs, and patients＇ cooperation during physical examination were assessed before and after 30 minutes of morphine or normal saline administration. Results Abdominal pain was significantly relieved and the patients＇ cooperation was improved in the morphine group after 30 minutes treatment compared with the control group and before morphine administration （P 〈0.05）. The physical signs were unaffected by either treatment （P 〉0.05）. Conclusions Morphine relieved abdominal pain and improved the patients＇ cooperation for treatment and care. Furthermore, the morphine did not mask the physical signs of acute appendicitis.     

Combined therapy with methylprednisolone and ulinastatin in experimental autoimmune encephalomyelitis

Background Our previous study had demonstrated that ulinastatin （UTI） had a neuroprotective effect in experimental autoimmune encephalomyelitis （EAE）. Methylprednisolone has been recommended to be a standard drug in multiple sclerosis （MS） therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE. Methods Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2＇,3＇-cyclic nucleotide 3＇- phosphodiesterase （CNP）/myelin basic protein （MBP）/the precursor form of nerve growth factor （proNGF）/p75/inducible nitric oxide synthase （iNOS） proteins in cerebral cortex of EAE were detected by Western blotting. Results The combined treatment group had a lower clinical score （0.61±0.06） and demyelinating score （1.33±0.33） than the groups with normal saline （clinical score： 1.39±0.08, P 〈0.001; demyelinating score： 2.75±0.49, P 〈0.05） or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP （1.14±0.06 vs. 0.65±0.04, P 〈0.001）, MBP （1.28±0.14 vs. 0.44±0.17, P 〈0.001）, and decreased expressions of proNGF （1.08±0.10 vs. 2.32±0.12, P 〈0.001）, p75 （1.13±0.13 vs. 2.33±0.17, P 〈0.001）, and iNOS （1.05±0.31 vs. 2.17±0.13, P 〈0.001） proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP （1.28±0.14 vs. 1.01±0.15, P 〈0.05） expression and downregulate iNOS （1.05±0.31 vs. 1.35±0.14, P 〈0.05） expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment （1.08±0.10） than that in UTI （1.51±0.24, P 〈0.05） or methylprednisolone （1.31±0.04, P 〈0.05） treatment group. Conclusion Combination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.     

Others——The effects of earlier resuscitation on following therapeutic response in sepsis with hypoperfusion

Objective To ealuate the effects of early sufficient resuscitation on important organs function and their therapenfic response in sepsis with hypoperfusion. Methods From January 2004 to December 2005,34 sepsis patients with hypoperfusion in surgical and respiratory intensive care units were resuscitated sufficiendy for the management of severe sepsis and septic shock. According to the time of resuscitation end points, these patients were diviede to early resuscitation group （E group, 15 patients） and later group （L group, 19 patients）. The important organs function and their therapeutic response followed resuseitation were investigated and compared in the tow groups. Resalts After earlier sufficient resuscitation, the incidence of repeated resuscitation was 73.7 % in L group and 20.0% in E group （ P 〈 0.01 ） ; the incidence of steroids replacement, coagulation dysfunction and multiple organ dysfunction syndrome （MODS） were 63. 2 %, 73.7 % and 68.4 % respectively in L group and significandy higher than those in Egroup （ P 〈 0.05 ）. Seven days after resuscitation, the level of serum creatinine in E group was lower than that in Lgroup （P〈0.05）. In the day i and 7 after resuscitation, heart rate in E group was lower than that in L group （ P 〈 0.05）. Seven days post resuscitation, PaO2 and PaO2/FiO2 were higher in E group than in L group （ P 〈 0.05）. The mortality was 42.1% in L group and 13.3% in E group （P〈0.05）. Conclusion Early sufficient resuscitation in sepsis patients with hypoperfusion could significantly enhance the effects of following treatment, relieve inflammation and coagulation reaction and thereby reduce the mortality. 7 refs,2 tabs.     

TCM Treatment of Male Immune Infertility——A Report of 100 Cases

To observe the therapeutic effect of Yikang Tang （益抗汤 Yikang Decoction） for male immune infertility. Methods： 100 cases of male immune infertility in the treatment group were treated with Yikang Decoction, while 100 cases treated with prednisone as the controls. Physical exam, routine semen and prostate exams, and exams for presence of anti-sperm antibody （AsAb） and mycoplasma in the serum or seminal plasma were carded out. Results： 1） The serum and seminal plasma AsAb levels decreased significantly （P〈0.01） in both the groups after treatment, with a more remarkable effect in the treatment group. 2） The sperm density and percentage of motile spermatozoa increased significantly in the two groups, but more significantly in the treatment group after treatment. The pregnancy rate of their wives was higher in the treatment group than that in the control group （P〈0.01）. 3） The sperm agglutination rate in the two groups decreased, but more significantly in the treatment group after treatment. 4） The improvement rate of the symptoms and the stability of the therapeutic effect were more dramatic in the treatment group than that in the control group （P〈0.01） after termination of drug administration. Conclusion： The Yikang Decoction has a more stable effect for male immune infertility than prednisone.     

Effect of Transcranial Magnetic Stimulation on the Expression of c-Fos and Brain-derived Neurotrophic Factor of the Cerebral Cortex in Rats with Cerebral Infarct

The effect of transcranial magnetic stimulation （TMS） on the neurological functional recovery and expression of c-Fos and brain-derived neurotrophic factor （BDNF） of the cerebral cortex in rats with cerebral infarction was investigated. Cerebral infarction models were established by using left middle cerebral artery occlusion （MCAO） and were randomly divided into a model group （n=40） and a TMS group （n=40）. TMS treatment （2 times per day, 30 pulses per time） with a frequency of 0.5 Hz and magnetic field intensity of 1.33 Tesla was carried out in TMS group after MCAO. Modified neurological severity score （NSS） were recorded before and 1, 7, 14, 21, and 28 day（s） after MCAO. The expression of c-Fos and BDNF was immunohistochemically detected 1, 7, 14, 21, and 28 day（s） after infarction respectively. Our results showed that a significant recovery of NSS （P〈0.05） was found in animals treated by TMS on day 7, 14, 21, and 28 as compared with the animals in the model group. The positive expression of c-Fos and BDNF was detected in the cortex surrounding the infarction areas, while the expression of c-Fos and BDNF increased significantly in TMS treatment group in comparison with those in model group 7, 14, 21, and 28 days （P〈0.05） and 7 14, 21 days （P〈0.01） after infarction, respectively. It is concluded that TMS has therapeutic effect on cerebral infarction and this may have something to do with TMS＇s ability to promote the expression of c-Fos and BDNF of the cerebral cortex in rats with cerebral infarction.     

Changes of Tumor Necrosis Factor-α and the Effects of Ulinastatin Injection during Cardiopulmonary Cerebral Resuscitation

The changes of tumor necrosis factor-a (TNF-a) and brain ultrastructure during cardiopulmonary resuscitation and the effects of ulinastation injection were observed, and the mechanism was investigated. Twenty-four adult healthy Sprague-Dawley rats were randomly divided into.control group (8 rats), resuscitation group (8 rats) and ulinastatin (UTI) group (8 rats). Rats in control group underwent tracheotomy without clipping the trachea to induce circulatory and respiratory standstill. Rats in resuscitation and ulinastatin group were subjected to the procedure of establishing the model of cardiopulmonary cerebral resuscitation (CPCR). Rats in ulinastatin group were given with UTI 104 U/kg once after CPCR. In the control group, the plasma was collected immediate,30 min, 2 h, 4 h, and 6 h after tracheotomy. In resuscitation group and UTI group, plasma was collected immediate after tracheotomy, 30 min, 2 h, 4 h and 6 h after successful resuscitation. The plasma levels of TNF-a were determined by radioimmunoassay (RIA). At the end of the experiment, 2 rats were randomly selected from each group and were decapitated, The cortex of the brain was taken out immediately to observe the ultrastructure changes. In control group, there were no significant differences in the level of TNF-a among different time points (P＞0.05). In resuscitation group, the level of TNF-a was increased obviously after resuscitation (P＜0.01) and reached its peak 2 h later after resuscitation. An increasing trend of TNF-a showed in UTI group. There were no differences in TNF-a among each sample taken after successful resuscitation and that after tracheotomy. The utrastructure of brains showed the injury in UTI group was ameliorated as compared with that in resuscitation group. In early period of CPCR, TNF-a was expressed rapidly and kept increasing. It indicated that TNF-a might take part in the tissue injury after CPCR. The administration of UTI during CACR could depress TNF-a and ameliorate brain injury. By regulating the expression of damaging mediator, UTI might provide a protective effect on the tissue injury after CPCR.     

Treatment of Heroinism with Acupuncture at Points of the Du Channel

To observe the effectiveness of acupuncture at points of the Du Channel in treating heroinism, seventy patients with heroinism were randomly divided into a treatment group （n = 35） and a control group （n=35）. A 10-day decrescendo therapy of methadone and acupuncture at points of the Du Channel were adopted in the treatment group, while the 10-day decrescendo therapy of methadone was simply performed in the control group. The scoring and grading of the abstinence symptoms were recorded and evaluated for both groups. 31 cases in the treatment group and 26 cases in the control group completed the entire treatment process, and a significant difference （P〈0.01） in scores of abstinence symptoms before and after treatment was noticed in the two groups. The obvious difference in scores of abstinence symptoms on the first, second, fifth, sixth, seventh, eighth, ninth and tenth day in the treatment group was superior to those in the control group （P〈0.05 or P〈0.01）. Particularly for such symptoms as perspiration, anxiety and pain in the muscle and bone, the result in the treatment group was much better than that in the control group （P〈0.05 or P〈0.01）. Acupuncture at points of the Du Channel has an auxiliary therapeutic effect on abstinence symptoms of heroinism, which can effectively help alleviate the abstinence symptoms.