AIM:To study the electrophysiological effects of amiodarone on the pacemaker cells in guinea-pig left ventricular outflow tract under the conditions of hypoxia,acidosis and treatment with epinephrine.METHODS:The action potentials of the pacemaker cells in guinea-pig left ventricular outflow tract were recorded by conventional intracellular microelectrode technique.The effects of amiodarone on the spontaneous slow response potentials were investigated under the conditions of hypoxia,acidosis and treatment with epinephrine.RESULTS:(1) Amiodarone at concentration of 0.1 ?mol/L markedly decreased the rate of pacemaker firing (RPF) and maximal diastolic potential (MDP),lengthened 80% of the duration of action potential (APD80).Amiodarone at concentration of 1 ?mol/L significantly decreased the velocity of diastolic depolarization (VDD) and RPF,the maximal rate of depolarization (Vmax),MDP and amplitude of action potential (APA),lengthened 50% of the duration of action potential (APD50) and APD80.Amiodarone at concentration of 10 ?mol/L led to a significant decrease in VDD and RPF,Vmax,MDP and APA,a notable lengthening in APD50 and APD80 was also observed.(2) Under the condition of hypoxia and perfusion with deprived glucose content for 15 min,VDD,RPF,MDP,Vmax and APA decreased significantly,APD50 was shortened notably.Under the condition of hypoxia,amiodarone at concentration of 1 ?mol/L significantly decreased VDD,RPF and Vmax,increased MDP,lengthened APD50 and APD80 as compared to the cells treated with hypoxia only.(3) Perfusion with pH 6.8 solution for 10 min,VDD and RPF significantly decreased,Vmax and APA notably reduced,APD80 was markedly shortened.Under the condition of acidosis for 10 min,amiodarone significantly decreased VDD,RPF,MDP and APA,lengthened APD50 and APD80 as compared to the cells under the condition of acidosis only.(4) Perfusion of epinephrine at concentration of 10 ?mol/L for 10 min resulted in a significant increase in VDD,RPF,Vmax,MDP and APA,a notable shorting in APD50 and APD80 was also observed.Compared to 10 ?mol/L epinephrine group,1 ?mol/L amiodarone+ 10 ?mol/L epinephrine significantly reduced VDD,RPF,Vmax,MDP and APA,lengthened APD50 and APD80.CONCLUSION:Amiodarone markedly decreases the autorhythmicity of the pacemaker cells in guinea-pig left ventricular outflow tract.This electrophysiological effects were significantly influenced by hypoxia,acidosis and epinephrine.

AIM:To observe the effects of normal mesenteric lymph (NML) on the lung, heart and liver inju-ries and the phosphorylation levels of p 38 mitogen-activated protein kinase ( MAPK) , extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) in the mice with endotoxic shock (ES).METHODS: The NML was drained form health male BALB/c mice for the intervention of ES after the removal of cellular constituent .Lipopolysaccha-ride (LPS, 35 mg/kg) was intraperitoneally injected into the mice for the establishment of ES model .After 60 min of LPS injection, the administration of NML (1/15 of whole blood volume) was performed through the femoral artery in NML +ES group.Meanwhile, the mean arterial pressure (MAP) was monitored during the experiment .At 6 h after intraperitoneal in-jection of LPS or the corresponding time point , blood samples were harvested from the heart through apical centesis for de-termination of the biochemical indexes to reflect myocardial and hepatocyte injuries .Simultaneously , the lung , heart and liver tissue specimens from a fixed location were harvested for the observation of histomorphology and the measurement of phosphorylation levels of p38 MAPK, ERK1/2 and JNK.RESULTS:Compared with sham shock (SS) group, MAP in ES group and NML+ES group remarkably decreased at multiple time points after intraperitoneal injection of LPS .However, MAP in NML+ES group at 80 min, 90 min, 190 min, 210 min, 240 min, 250 min, 340 min, 350 min, and 360 min were significantly increased compared with ES group .There were normal structures in the lung , liver and myocardium of the mice in SS group, while the morphological damages of these tissues appeared in ES group .Meanwhile, the damages were attenuated in the mice of NML +ES group.The activities of AST , ALT and CK-MB in the plasma in ES group were remark-ably higher than those in SS group .The CK-MB activity in NML+ES group was also increased compared with SS group , and the activities of AST and LDH-1 were lower than those in ES group .At 6 h after LPS injection , the phosphorylation levels of p38 MAPK, ERK1/2 and JNK in the lung tissues were remarkably increased .Meanwhile , no statistical difference of these indexes between the myocardial and hepatic tissues was observed .NML intervention decreased the phosphorylation levels of p38 MAPK in the lung tissues , and p38 MAPK, ERK1/2 and JNK in the myocardial tissues .CONCLUSION:The NML administration alleviates multi-organ injuries and reduces the phosphorylation level of p 38 MAPK in the lung tis-sues in the mice subjected to ES .

AIM: To investigate the role of post-hemorrhagic shock mesenteric lymph (PHSML) in the enhancementof vascular permeability .METHODS: Eighteen Wistar rats were randomized into sham group , shock group,and shock plus mesenteric lymph drainage (shock +drainage) group.The rats in shock group and shock +drainagegroup were routinely subjected to hemorrhagic shock and hypotension [(40 ±2) mmHg] was maintained for 90 min, andthen the fluid resuscitation was performed.Mesenteric lymph was drained in the rats in shock +drainage group from resuscitationfinished to 6 h, for the observation of PHSML drainage on the vascular permeability in multiple tissues of hemorrhagicshock rats.Afterwards, human umbilical vein endothelial cells (HUVECs) were incubated with the PHSML in vitro to observethe effects of PHSML on the morphology and permeability of HUVECs .RESULTS: The degree of blue color and concentrationsof Evens blue in the lung, myocardium, kidney, liver, spleen and small intestine were significantly increased inthe shocked rats than that in sham group, while the ratios of the dry weight to the wet weight were decreased .The mesentericlymph drainage reversed these changes .Meanwhile, 4% and 10% of PHSML at 0 ~3 h and 3 ~6 h after resuscitation,and lipopolysaccharide (10 mg/L) all caused the damage of HUVECs, decreased the viability and trans-endothelial electricalresistance of HUVECs, and increased the permeability of HUVECs to fluorescein isothiocyanate -labeled albumin. CONCLUSION: PHSML is a vital factor in the enhancement of vascular permeability .

Objective:To evaluate clinical efficacy and safety of immunotherapy by retrospectively analyzing clinical medica-tion of patients with recurrent pregnancy loss(RPL)complicated with abnormal immune factors.Methods:A retrospective cohort study was conducted on RPL cases in outpatient department of Hebei Reproductive Health Hospital from January 2021 to April 2022.Efficacy and safety of immunotherapy were evaluated from pregnancy outcome,adverse reactions and birth defects of offspring.Results:According to guidelines,192 cases with abnormal autoimmunity and/or immune indicators were included.Early abortion rate was 4.16%in group of two lost pregnancies,which was lower than that in group of three lost pregnancies(16.66%).Twelve week sus-tained pregnancy rate was 89.58%in the former group,and 28 week sustained pregnancy rate was 86.45%,which were significantly higher than those in the latter group(75.00%,71.87%).RPL patients were divided into groups according to their exposure to immuno-modulatory drugs before 12 weeks of pregnancy.There was no significant difference in pregnancy outcome,adverse reaction rate and birth defect rate of their offspring(P>0.05).Conclusion:Immunotherapy can effectively reduce risk of recurrent abortion and increase rate of persistent pregnancy in patients with immune RPL.Personalized immunotherapy can make RPL patients with immune factors achieve expected effect of fetal protection.

Objective:To summarize the medium-term outcomes of single kidney transplantation from senile deceased donors aged above 65 years.Methods:Forty-three kidney recipients from donors aged above 65(old-aged donor group, OAD) and 43 kidney recipients of the same age and gender from donors aged 18 to 49 years(standard-criteria donor group, SCD) were retrospectively reviewed.The survival outcomes of patients and grafts, renal functions, the incidence of delayed graft function(DGF)and other complications were recorded within the 3-year follow-up post-transplantation.Results:The 3-year patient survival rates were 95.3% both in OAD and SCD and the 3-year death-censored graft survival rates 92.7% and 97.6% respectively.The serum levels of creatinine were significantly higher in OAD than that in SCD( P<0.05). And lower estimated glomerular filtration rate(eGFR)was found in OAD as compared with SCD( P<0.05). No significant difference existed in the incidence of DGF(OAD 20.9% and SCD 18.6%, P>0.05), acute rejection (OAD 4.7% and SCD 2.3%, P>0.05)or proteinuria(OAD 27.9%and SCD 14.0%, P>0.05). Conclusions:Single kidney transplantation from old-aged deceased donors may achieve excellent medium-term survival outcomes of patients and grafts.It can expand the donor pool though kidney functions were not as good as those of SCD.

Objective : To explore the method of intraperitoneal injection of allogenic fecal filtrate to establish the rat model of moderate and severe sepsis． Methods: The preparation method of allogeneic fecal filtrate was determined．Allogeneic fecal filtrate of different concentrations (0. 5，1，2 g / kg) was injected intraperitoneally to observe the general situation，survival time and severe degree of sepsis of rats. After determining the optimal concentration，the success rate of the model，serum inflammatory factors，serum concentration of D-lactic acid ( D-LA) and serum intestinal fatty acid binding protein (I-FABP) ，lung function changes，lung，liver and kidney tissue injury were further observed. Results: After intraperitoneal injection of allogenic fecal filtrate for 24 h，the rats of 1 g / kg group presented fever，tachypnea and hypotension，the survival rate was 83. 3% at 24 h and 16. 7% at 48 h， 2 g / kg group rats all died within 24 h，the dose of 1 g / kg was determined for subsequent experiments．Injected fecal filtrate for 24 h，the success rate of the sepsis model was 77. 8% . The levels of interleukin-6 ( IL-6) ，tumor necrosis factor-α ( TNF-α) ，D-LA and I-FABP in serum significantly increased． There were severe edema and bleeding in lung tissue，Pulmonary function appeared respiratory dysfunction，included functional residual capacity (FRC) ，quasi static compliance ( Cdyn) ，forced expiratory volume for the first 100 milliseconds(FEV100) ，peak expiratory flow (PEF) decreased，airway resistance (RI) ，inspiratory capacity (IC) increased．Liver and kidney tissues also showed varying degrees of edema and inflammatory cell infiltration，the levels of alanine aminotransferase (ALT) ，aspartate aminotransferase (AST) ，blood urea nitrogen (BUN) and creatinine ( Cr) in serum significantly increased． Conclusion Intraperitoneal injection of allogenic fecal filtrate ( 1 g / kg) can produce a relative typical septic model in rats.

OBJECTIVE： To provide reference for improving emergency capacity of the hospital pharmacy department in response to the novel coronavirus pneumonia （COVID-19） epidemic. METHODS ：According to the related regulations and requirements of Law of the People ’s Republic of China on the Prevention and Control of Infectious Diseases ，combined with the situation of COVID- 19 epidemic prevention and control ，and management experience of relevant hospitals ，on the basis of in-depth analysis of drug supply and quality assurance ，drug dispensing management ，provision of clinical pharmaceutical services and other related material support of hospital pharmacy department，integrated emergency management model was constructed for COVID- 19 epidemic prevention and control ，and the precautions and response measures of each link were sorted out. RESULTS ：Integruted emergency management mode for COVID-19 epidemic prevention and control in hospital pharmacy department included but was not limited to human resource management，drug and disinfection products supply management （mainly including key treatment drugs and disinfection product list formulation，control，inventory increase ，etc.）；drug dispensing management （mainly including prescription ，pharmacy window ， planning quantitative reserve ， drug return ， etc.）；clinical pharmaceutical care management （mainly including providing pharmaceutical information support ，online pharmaceutical service ，monitoring drug safety ，etc.）；personnel protection and disinfection （mainly including personnel protection ，environment and window ，equipment and container ，paper prescription disinfection，etc.）；special management of donated drugs ；prevention and control knowledge training ；pharmaceutical education and scientific research management ，etc. CONCLUSIONS ：The integrated emergency management model for epidemic prevention and control is helpful for hospital pharmacy to manage public health emergencies. During the outbreak of COVID- 19，hospital pharmacy department should start integrated emergency management mode for epidemic prevention and control ，strengthen the risk control of each link ，and play a good role in the key functional departments in the special period.