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 detect the expression levels of various immune cells in peripheral blood,and to ex-plore their relationship with unexplained recurrent spontaneous abortion(URSA)and its clinical significance in di-agnosis and treatment.Methods:A total of 351 patients with URSA who visited Hebei Reproductive Health Hospi-tal between January 2020 and September 2022 were enrolled as the URSA group,while a control group compri-sing 30 healthy women who had experienced uncomplicated term delivery once and had no history of adverse pregnancy outcomes during the same period was selected.The levels of various immune cell subsets in peripheral blood during the luteal phase were measured and compared between the two groups.Receiver operating charac-teristic(ROC)curve analysis was performed to determine the optimal cutoff values of immune cell levels that could assist in URSA diagnosis and treatment,while logistic regression analysis was conducted to identify factors influ-encing URSA occurrence.Results:The number and percentage of CD3+CD8+cells in the peripheral blood of the URSA group were significantly lower compared to those in the control group(P＜0.05).Conversely,the per-centage of NK cells was significantly higher in the URSA group than in the control group(P＜0.05).Logistic re-gression analysis revealed that the increase in CD3+CD8+cell count in peripheral blood during the luteal phase was a protective factor of URSA(OR＜1,P＜0.05).ROC curve analysis determined optimal cutoff values for im-mune cell levels to assist in the diagnosing and treating URSA:702.82 cells/μl for CD3+CD8+cell count,28.39％for CD3+CD8+cell percentage,and 12.33％for NK cell percentage.After using the optimal cutoff value to convert continuous variables into binary variables,Logistic regression analysis showed that a CD3+CD8+cell count＜702.82 cells/μl and an NK cell percentage＞12.33％were independent risk factors for URSA(OR＞1,P＜0.05).Conclusions:The decrease of CD3+CD8+cells in peripheral blood during midluteal phase is closely related to the occurrence of URSA.The number of CD3+CD8+cells(702.82 cells/μl)and the percentage of NK cells(12.33％)can be used as reference values for the diagnosis and treatment of URSA.

Objective:To detect the expression levels of various immune cells in peripheral blood,and to ex-plore their relationship with unexplained recurrent spontaneous abortion(URSA)and its clinical significance in di-agnosis and treatment.Methods:A total of 351 patients with URSA who visited Hebei Reproductive Health Hospi-tal between January 2020 and September 2022 were enrolled as the URSA group,while a control group compri-sing 30 healthy women who had experienced uncomplicated term delivery once and had no history of adverse pregnancy outcomes during the same period was selected.The levels of various immune cell subsets in peripheral blood during the luteal phase were measured and compared between the two groups.Receiver operating charac-teristic(ROC)curve analysis was performed to determine the optimal cutoff values of immune cell levels that could assist in URSA diagnosis and treatment,while logistic regression analysis was conducted to identify factors influ-encing URSA occurrence.Results:The number and percentage of CD3+CD8+cells in the peripheral blood of the URSA group were significantly lower compared to those in the control group(P＜0.05).Conversely,the per-centage of NK cells was significantly higher in the URSA group than in the control group(P＜0.05).Logistic re-gression analysis revealed that the increase in CD3+CD8+cell count in peripheral blood during the luteal phase was a protective factor of URSA(OR＜1,P＜0.05).ROC curve analysis determined optimal cutoff values for im-mune cell levels to assist in the diagnosing and treating URSA:702.82 cells/μl for CD3+CD8+cell count,28.39％for CD3+CD8+cell percentage,and 12.33％for NK cell percentage.After using the optimal cutoff value to convert continuous variables into binary variables,Logistic regression analysis showed that a CD3+CD8+cell count＜702.82 cells/μl and an NK cell percentage＞12.33％were independent risk factors for URSA(OR＞1,P＜0.05).Conclusions:The decrease of CD3+CD8+cells in peripheral blood during midluteal phase is closely related to the occurrence of URSA.The number of CD3+CD8+cells(702.82 cells/μl)and the percentage of NK cells(12.33％)can be used as reference values for the diagnosis and treatment of URSA.

Objective:To detect the expression levels of various immune cells in peripheral blood,and to ex-plore their relationship with unexplained recurrent spontaneous abortion(URSA)and its clinical significance in di-agnosis and treatment.Methods:A total of 351 patients with URSA who visited Hebei Reproductive Health Hospi-tal between January 2020 and September 2022 were enrolled as the URSA group,while a control group compri-sing 30 healthy women who had experienced uncomplicated term delivery once and had no history of adverse pregnancy outcomes during the same period was selected.The levels of various immune cell subsets in peripheral blood during the luteal phase were measured and compared between the two groups.Receiver operating charac-teristic(ROC)curve analysis was performed to determine the optimal cutoff values of immune cell levels that could assist in URSA diagnosis and treatment,while logistic regression analysis was conducted to identify factors influ-encing URSA occurrence.Results:The number and percentage of CD3+CD8+cells in the peripheral blood of the URSA group were significantly lower compared to those in the control group(P＜0.05).Conversely,the per-centage of NK cells was significantly higher in the URSA group than in the control group(P＜0.05).Logistic re-gression analysis revealed that the increase in CD3+CD8+cell count in peripheral blood during the luteal phase was a protective factor of URSA(OR＜1,P＜0.05).ROC curve analysis determined optimal cutoff values for im-mune cell levels to assist in the diagnosing and treating URSA:702.82 cells/μl for CD3+CD8+cell count,28.39％for CD3+CD8+cell percentage,and 12.33％for NK cell percentage.After using the optimal cutoff value to convert continuous variables into binary variables,Logistic regression analysis showed that a CD3+CD8+cell count＜702.82 cells/μl and an NK cell percentage＞12.33％were independent risk factors for URSA(OR＞1,P＜0.05).Conclusions:The decrease of CD3+CD8+cells in peripheral blood during midluteal phase is closely related to the occurrence of URSA.The number of CD3+CD8+cells(702.82 cells/μl)and the percentage of NK cells(12.33％)can be used as reference values for the diagnosis and treatment of URSA.

Objective:To detect the expression levels of various immune cells in peripheral blood,and to ex-plore their relationship with unexplained recurrent spontaneous abortion(URSA)and its clinical significance in di-agnosis and treatment.Methods:A total of 351 patients with URSA who visited Hebei Reproductive Health Hospi-tal between January 2020 and September 2022 were enrolled as the URSA group,while a control group compri-sing 30 healthy women who had experienced uncomplicated term delivery once and had no history of adverse pregnancy outcomes during the same period was selected.The levels of various immune cell subsets in peripheral blood during the luteal phase were measured and compared between the two groups.Receiver operating charac-teristic(ROC)curve analysis was performed to determine the optimal cutoff values of immune cell levels that could assist in URSA diagnosis and treatment,while logistic regression analysis was conducted to identify factors influ-encing URSA occurrence.Results:The number and percentage of CD3+CD8+cells in the peripheral blood of the URSA group were significantly lower compared to those in the control group(P＜0.05).Conversely,the per-centage of NK cells was significantly higher in the URSA group than in the control group(P＜0.05).Logistic re-gression analysis revealed that the increase in CD3+CD8+cell count in peripheral blood during the luteal phase was a protective factor of URSA(OR＜1,P＜0.05).ROC curve analysis determined optimal cutoff values for im-mune cell levels to assist in the diagnosing and treating URSA:702.82 cells/μl for CD3+CD8+cell count,28.39％for CD3+CD8+cell percentage,and 12.33％for NK cell percentage.After using the optimal cutoff value to convert continuous variables into binary variables,Logistic regression analysis showed that a CD3+CD8+cell count＜702.82 cells/μl and an NK cell percentage＞12.33％were independent risk factors for URSA(OR＞1,P＜0.05).Conclusions:The decrease of CD3+CD8+cells in peripheral blood during midluteal phase is closely related to the occurrence of URSA.The number of CD3+CD8+cells(702.82 cells/μl)and the percentage of NK cells(12.33％)can be used as reference values for the diagnosis and treatment of URSA.

Objective:To detect the expression levels of various immune cells in peripheral blood,and to ex-plore their relationship with unexplained recurrent spontaneous abortion(URSA)and its clinical significance in di-agnosis and treatment.Methods:A total of 351 patients with URSA who visited Hebei Reproductive Health Hospi-tal between January 2020 and September 2022 were enrolled as the URSA group,while a control group compri-sing 30 healthy women who had experienced uncomplicated term delivery once and had no history of adverse pregnancy outcomes during the same period was selected.The levels of various immune cell subsets in peripheral blood during the luteal phase were measured and compared between the two groups.Receiver operating charac-teristic(ROC)curve analysis was performed to determine the optimal cutoff values of immune cell levels that could assist in URSA diagnosis and treatment,while logistic regression analysis was conducted to identify factors influ-encing URSA occurrence.Results:The number and percentage of CD3+CD8+cells in the peripheral blood of the URSA group were significantly lower compared to those in the control group(P＜0.05).Conversely,the per-centage of NK cells was significantly higher in the URSA group than in the control group(P＜0.05).Logistic re-gression analysis revealed that the increase in CD3+CD8+cell count in peripheral blood during the luteal phase was a protective factor of URSA(OR＜1,P＜0.05).ROC curve analysis determined optimal cutoff values for im-mune cell levels to assist in the diagnosing and treating URSA:702.82 cells/μl for CD3+CD8+cell count,28.39％for CD3+CD8+cell percentage,and 12.33％for NK cell percentage.After using the optimal cutoff value to convert continuous variables into binary variables,Logistic regression analysis showed that a CD3+CD8+cell count＜702.82 cells/μl and an NK cell percentage＞12.33％were independent risk factors for URSA(OR＞1,P＜0.05).Conclusions:The decrease of CD3+CD8+cells in peripheral blood during midluteal phase is closely related to the occurrence of URSA.The number of CD3+CD8+cells(702.82 cells/μl)and the percentage of NK cells(12.33％)can be used as reference values for the diagnosis and treatment of URSA.

Objective:To detect the expression levels of various immune cells in peripheral blood,and to ex-plore their relationship with unexplained recurrent spontaneous abortion(URSA)and its clinical significance in di-agnosis and treatment.Methods:A total of 351 patients with URSA who visited Hebei Reproductive Health Hospi-tal between January 2020 and September 2022 were enrolled as the URSA group,while a control group compri-sing 30 healthy women who had experienced uncomplicated term delivery once and had no history of adverse pregnancy outcomes during the same period was selected.The levels of various immune cell subsets in peripheral blood during the luteal phase were measured and compared between the two groups.Receiver operating charac-teristic(ROC)curve analysis was performed to determine the optimal cutoff values of immune cell levels that could assist in URSA diagnosis and treatment,while logistic regression analysis was conducted to identify factors influ-encing URSA occurrence.Results:The number and percentage of CD3+CD8+cells in the peripheral blood of the URSA group were significantly lower compared to those in the control group(P＜0.05).Conversely,the per-centage of NK cells was significantly higher in the URSA group than in the control group(P＜0.05).Logistic re-gression analysis revealed that the increase in CD3+CD8+cell count in peripheral blood during the luteal phase was a protective factor of URSA(OR＜1,P＜0.05).ROC curve analysis determined optimal cutoff values for im-mune cell levels to assist in the diagnosing and treating URSA:702.82 cells/μl for CD3+CD8+cell count,28.39％for CD3+CD8+cell percentage,and 12.33％for NK cell percentage.After using the optimal cutoff value to convert continuous variables into binary variables,Logistic regression analysis showed that a CD3+CD8+cell count＜702.82 cells/μl and an NK cell percentage＞12.33％were independent risk factors for URSA(OR＞1,P＜0.05).Conclusions:The decrease of CD3+CD8+cells in peripheral blood during midluteal phase is closely related to the occurrence of URSA.The number of CD3+CD8+cells(702.82 cells/μl)and the percentage of NK cells(12.33％)can be used as reference values for the diagnosis and treatment of URSA.