human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: During acupuncture treatments , acupuncture needles are manipulated to elicit the characteristic " de qi " reaction widely viewed as essential to acupuncture 's therapeutic effect . De qi has a biomechanical component , " needle grasp , " which we have quantified by measuring the force necessary to pull an acupuncture needle out of the skin ( pullout force ) in 60 human subjects . We hypothesized that pullout force is greater with both bidirectional needle rotation ( BI ) and unidirectional rotation ( UNI ) than no rotation ( NO ) . Acupuncture needles were inserted , manipulated , and pulled out by using a computer-controlled acupuncture needling instrument at eight acupuncture points and eight control points . We found 167 and 52 % increases in mean pullout force with UNI and BI , respectively , compared with NO ( repeated- measures ANOVA , P < 0.001 ) . Pullout force was on average 18 % greater at acupuncture points than at control points ( P < 0.001 ) . Needle grasp is therefore a measurable biomechanical phenomenon associated with acupuncture needle manipulation Objective Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept , human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 ( TNFR55-IgG1 ) fusion protein , decreased mortality in patients with severe sepsis or early septic shock . Design Multicenter , double-blind , phase III , placebo-controlled , r and omized study . Setting A total of 108 community and university-affiliated hospitals in the United States ( 60 ) , Canada ( 6 ) and Europe ( 42 ) . Patients A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration . InterventionAfter r and omization , an intravenous dose of 0.125 mg/kg lenercept or placebo was given . The patient was monitored for up to 28 days , during which st and ard diagnostic , supportive , and therapeutic care was provided . Measurements and Main Results The primary outcome measure was 28-day all-cause mortality . Baseline characteristics were as follows : a total of 1,342 patients were r and omized ; 662 received lenercept and 680 received placebo . The mean age was 60.5 yrs ( range , 17–96 yrs ) ; 39 % were female ; 65 % had medical admissions , 8 % had scheduled surgical admissions , and 27 % had unscheduled surgical admissions ; 73 % had severe sepsis without shock , and 27 % had severe sepsis with early septic shock .  Lenercept and placebo groups were similar at baseline with respect to demographic characteristics , simplified acute physiology score II-predicted mortality , profiles of clinical site of infection and microbiological documentation , number of dysfunctioning organs , and interleukin-6 ( IL-6 ) plasma concentration . Lenercept  pharmacokinetics were similar in severe sepsis and early septic shock patients . Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor & agr ; concentrations . There were 369 deaths , 177 on lenercept ( 27 % mortality ) and 192 on placebo ( 28 % mortality ) . A one-sided Cochran-Armitage test , stratified by geographic region and baseline , predicted 28-day all-cause mortality ( simplified acute physiology score II ) , gave a p value of .141 ( one-sided ) . Lenercept treatment had no effect on incidence or resolution of organ dysfunctions . There was no evidence that lenercept was detrimental in the overall population . Conclusion Lenercept had no significant effect on mortality in the study population OBJECTIVE To explore protective effects of acupuncture at " Zusanli " ( ST 36 ) on cerebral tissue in rats with sepsis . METHODS Cecal ligation and puncture ( CLP ) was applied to duplicate the rat model of sepsis . According to r and om number table , thirty SD rats were divided into a sepsis model group ( group A ) , a sepsis model plus electroacupuncture ( EA ) group ( group B ) , and a sepsis model plus non-acupoint EA group ( group C ) , ten rats in each one . EA with the same frequency and intensity at " Zusanli " ( ST 36 ) and non-acupoint ( 0.5 cm laterally to " Zusanli " ) for 30 min was applied in the group B and group C , respectively . No treatment was given in the goup A. 6 hours after CLP , blood was acquired from abdominal aorta to measure the levels of neuron specific enolase ( NSE ) . Then the rats were sacrificed by abdominal aorta exsanguination to take their cerebral tissue for measuring the levels of tumor necrosis factor-alpha ( TNF-alpha ) and interleukin-6 ( IL-6 ) . RESULTS Six hours after CLP , the level of NSE was ( 3.51 + /- 0.39 ) ng/mL in group B , which was significantly lower than ( 7.72 + /- 0.64 ) ng/mL in group A ( P<0.05 ) . The level of NSE was ( 8.02 + /- 0.72 ) ng/mL in the group C , which had no statistical significance with group A ( P>0.05 ) . The levels of TNF-alpha , IL-6 in cerebral tissue in group B were significantly lower than that of group A and C ( all P>0.05 ) . CONCLUSION EA at " Zusanli " ( ST 36 ) has certain protective effect on septic rat 's brain , which has some relationship with decreasing levels of cerebral tissue proinflammatory cytokine and plasma NSE .  EA at non-acupoint has no the same action NF-E2 related factor 2 ( Nrf2 ) is a major transcription factor and acts as a key regulator of antioxidant genes to exogenous stimulations . The aim of current study was to determine whether Nrf2/ARE pathway is involved in the protective effect of electroacupuncture on the injured lung in a rabbit model of endotoxic shock . A dose of lipopolysaccharide ( LPS ) 5 mg/kg was administered intravenously to replicate the model of acute lung injury induced by endotoxic shock . Electroacupuncture pretreatment was h and led bilaterally at Zusanli and Feishu acupoints for five consecutive days while sham electroacupuncture punctured at non-acupoints . Fourty anesthetized New Engl and male rabbits were r and omized into normal control group ( group C ) , LPS group ( group L ) , electroacupuncture + LPS group ( group EL ) and sham electroacupuncture + LPS ( group SEL ) . At 6 h after LPS administration , the animals were sacrificed and the blood sample s were collected for biochemical measurements . The lungs were removed for calculation of wet-to-dry weight ratios ( W/D ) , histopathologic examination , determination of heme oxygenase (HO)-1 protein and mRNA , Nrf2 total and nucleoprotein , as well as Nrf2 mRNA expression , and evaluation of the intracellular distribution of Nrf2 nucleoprotein . LPS caused extensive morphologic lung damage , which was lessened by electroacupuncture treatment . Besides , lung W/D ratios were significantly decreased , the level of malondialdehyde was inhibited , plasma levels of TNF-α and interleukin-6 were decreased , while the activities of superoxide dismutase , glutathione peroxidase and catalase were enhanced in the electroacupucnture treated animals . In addition , electroacupuncture stimulation distinctly increased the expressions of HO-1 and Nrf2 protein including Nrf2 total protein and nucleoprotein as well as mRNA in lung tissue , while these effects were blunted in the sham electroacupuncture group . We concluded that electroacupuncture treatment at ST36 and BL13 effectively attenuates lung injury in a rabbit model of endotoxic shock through activation of Nrf2/ARE pathway and following up-regulation of HO-1 expression Background The anti-oxidative and anti-inflammatory activities of electro-acupuncture ( EA ) , a traditional clinical method , are widely accepted , but its mechanisms are not yet well defined . In this study , we investigated the role of extracellular signal-regulated kinases1/2 ( ERK1/2 ) pathways on electro-acupuncture – mediated up-regulation of heme oxygenase-1 ( HO-1 ) in rabbit lungs injured by LPS-induced endotoxic shock . Material / Methods Seventy rabbits were r and omly divided into 7 groups : group C , group M , group D , group SEAM , group EAM , group EAMPD , and group PD98059 .  Male New Engl and white rabbits were given EA treatment on both sides once a day on days 1–5 , and then received LPS to replicate the experimental model of injured lung induced by endotoxic shock . Then , they were killed by exsanguination at 6 h after LPS administration . The blood sample s were collected for serum examination , and the lungs were removed for pathology examination , determination of wet-to-dry weight ratio , MDA content , SOD activity , serum tumor necrosis factor-α , determination of HO-1 protein and mRNA expression , and determination of ERK1/2 protein . Results The results revealed that after EA  treatment , expression of HO-1 and ERK1/2 was slightly increased compared to those in other groups , accompanied with less severe lung injury as indicated by lower index of lung injury score , lower wet-to-dry weight ratio , MDA content , and serum tumor necrosis factor-α levels , and greater SOD activity ( p<0.05 for all ) . After pretreatment with ERK1/2 inhibitor PD98059 , the effect of EA treatment and expression of HO-1 were suppressed ( p<0.05 for all ) . Conclusions After electro-acupuncture stimulation at ST36 and BL13 , severe lung injury during endotoxic shock was attenuated . The mechanism may be through up-regulation of HO-1 , mediated by the signal transductions of ERK1/2 pathways . Thus , the regulation of ERK1/2 pathways via electro-acupuncture may be a therapeutic strategy for endotoxic shock Although systematic studies have demonstrated that acupuncture or electroacupuncture ( EA ) analgesia is based on their accelerating endogenous opioid release to activate opioid receptors and that EA of different frequencies is mediated by different opioid receptors in specific areas of the central nervous system , there is little direct , real-time evidence to confirm this in vivo . The present study was design ed to investigate the effects of transcutaneous electrical acupoint stimulation ( TEAS ) , an analogue of EA , at low and high frequencies on μ-opioid receptor ( MOR ) availability in the brain of rhesus monkeys . Monkeys underwent 95-min positron emission tomography ( PET ) with ( 11 ) C-carfentanil three times r and omly while receiving 0 , 2 , or 100 Hz TEAS , respectively . Each TEAS was administered in the middle 30 min during the 95-min PET scan , and each session of PET and TEAS was separated by at least 2 weeks . The results revealed that 2 Hz but not 100 Hz TEAS evoked a significant increase in MOR binding potential in the anterior cingulate cortex , the cau date nucleus , the putamen , the temporal lobe , the somatosensory cortex , and the amygdala compared with 0 Hz TEAS . The effect remained after the end of TEAS in the anterior cingulate cortex and the temporal lobe . The selective increase in MOR availability in multiple brain regions related to pain and sensory processes may play a role in mediating low-frequency TEAS efficacy Heme oxygenase (HO)-1 has been reported to play a great role in attenuating lung injury during endotoxic shock in our previous research . Although electro-acupuncture has been explored to reduce oxidative stress and decrease inflammatory reaction in animals with endotoxic shock , the mechanism of this effect is still unclear . The aim of this study was to determine whether HO-1 is involved in the effect of electro-acupuncture on the injured lung during endotoxic shock in rabbits . Sixty New Engl and white rabbits were r and omly divided into groups C , Z , ES , EA , AP , and EAZ . Before inducing endotoxic shock , group ES received no electro-acupuncture , while group EA received electro-acupuncture at ST36 ( zusanli ) and BL13 ( feishu ) acupoints on both sides for five days and group AP received electro-acupuncture ( EA ) stimulation at a non-acupoint . Groups ES , AP , EA , and EAZ received LPS to replicate the experimental model of injured lung induced by endotoxic shock , and electro-acupuncture was performed throughout the procedure with the same parameter . Groups EAZ and Z received the HO-1 inhibitor , ZnPP-IX , intraperitoneally . The animals were sacrificed by blood-letting at 6 h after LPS administration . The blood sample s were collected for serum examination , and the lungs were removed for pathology examination , detection of alveolaer epithelial cell apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay ( TUNEL assay ) , determination of wet to dry ratio , 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: During acupuncture treatments , acupuncture needles are manipulated to elicit the characteristic " de qi " reaction widely viewed as essential to acupuncture 's therapeutic effect . De qi has a biomechanical component , " needle grasp , " which we have quantified by measuring the force necessary to pull an acupuncture needle out of the skin ( pullout force ) in 60 human subjects . We hypothesized that pullout force is greater with both bidirectional needle rotation ( BI ) and unidirectional rotation ( UNI ) than no rotation ( NO ) . Acupuncture needles were inserted , manipulated , and pulled out by using a computer-controlled acupuncture needling instrument at eight acupuncture points and eight control points . We found 167 and 52 % increases in mean pullout force with UNI and BI , respectively , compared with NO ( repeated- measures ANOVA , P < 0.001 ) . Pullout force was on average 18 % greater at acupuncture points than at control points ( P < 0.001 ) . Needle grasp is therefore a measurable biomechanical phenomenon associated with acupuncture needle manipulation Objective Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept , human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 ( TNFR55-IgG1 ) fusion protein , decreased mortality in patients with severe sepsis or early septic shock . Design Multicenter , double-blind , phase III , placebo-controlled , r and omized study . Setting A total of 108 community and university-affiliated hospitals in the United States ( 60 ) , Canada ( 6 ) and Europe ( 42 ) . Patients A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration . InterventionAfter r and omization , an intravenous dose of 0.125 mg/kg lenercept or placebo was given . The patient was monitored for up to 28 days , during which st and ard diagnostic , supportive , and therapeutic care was provided . Measurements and Main Results The primary outcome measure was 28-day all-cause mortality . Baseline characteristics were as follows : a total of 1,342 patients were r and omized ; 662 received lenercept and 680 received placebo . The mean age was 60.5 yrs ( range , 17–96 yrs ) ; 39 % were female ; 65 % had medical admissions , 8 % had scheduled surgical admissions , and 27 % had unscheduled surgical admissions ; 73 % had severe sepsis without shock , and 27 % had severe sepsis with early septic shock .  Lenercept and placebo groups were similar at baseline with respect to demographic characteristics , simplified acute physiology score II-predicted mortality , profiles of clinical site of infection and microbiological documentation , number of dysfunctioning organs , and interleukin-6 ( IL-6 ) plasma concentration . Lenercept  pharmacokinetics were similar in severe sepsis and early septic shock patients . Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor & agr ; concentrations . There were 369 deaths , 177 on lenercept ( 27 % mortality ) and 192 on placebo ( 28 % mortality ) . A one-sided Cochran-Armitage test , stratified by geographic region and baseline , predicted 28-day all-cause mortality ( simplified acute physiology score II ) , gave a p value of .141 ( one-sided ) . Lenercept treatment had no effect on incidence or resolution of organ dysfunctions . There was no evidence that lenercept was detrimental in the overall population . Conclusion Lenercept had no significant effect on mortality in the study population OBJECTIVE To explore protective effects of acupuncture at " Zusanli " ( ST 36 ) on cerebral tissue in rats with sepsis . METHODS Cecal ligation and puncture ( CLP ) was applied to duplicate the rat model of sepsis . According to r and om number table , thirty SD rats were divided into a sepsis model group ( group A ) , a sepsis model plus electroacupuncture ( EA ) group ( group B ) , and a sepsis model plus non-acupoint EA group ( group C ) , ten rats in each one . EA with the same frequency and intensity at " Zusanli " ( ST 36 ) and non-acupoint ( 0.5 cm laterally to " Zusanli " ) for 30 min was applied in the group B and group C , respectively . No treatment was given in the goup A. 6 hours after CLP , blood was acquired from abdominal aorta to measure the levels of neuron specific enolase ( NSE ) . Then the rats were sacrificed by abdominal aorta exsanguination to take their cerebral tissue for measuring the levels of tumor necrosis factor-alpha ( TNF-alpha ) and interleukin-6 ( IL-6 ) . RESULTS Six hours after CLP , the level of NSE was ( 3.51 + /- 0.39 ) ng/mL in group B , which was significantly lower than ( 7.72 + /- 0.64 ) ng/mL in group A ( P<0.05 ) . The level of NSE was ( 8.02 + /- 0.72 ) ng/mL in the group C , which had no statistical significance with group A ( P>0.05 ) . The levels of TNF-alpha , IL-6 in cerebral tissue in group B were significantly lower than that of group A and C ( all P>0.05 ) . CONCLUSION EA at " Zusanli " ( ST 36 ) has certain protective effect on septic rat 's brain , which has some relationship with decreasing levels of cerebral tissue proinflammatory cytokine and plasma NSE .  EA at non-acupoint has no the same action NF-E2 related factor 2 ( Nrf2 ) is a major transcription factor and acts as a key regulator of antioxidant genes to exogenous stimulations . The aim of current study was to determine whether Nrf2/ARE pathway is involved in the protective effect of electroacupuncture on the injured lung in a rabbit model of endotoxic shock . A dose of lipopolysaccharide ( LPS ) 5 mg/kg was administered intravenously to replicate the model of acute lung injury induced by endotoxic shock . Electroacupuncture pretreatment was h and led bilaterally at Zusanli and Feishu acupoints for five consecutive days while sham electroacupuncture punctured at non-acupoints . Fourty anesthetized New Engl and male rabbits were r and omized into normal control group ( group C ) , LPS group ( group L ) , electroacupuncture + LPS group ( group EL ) and sham electroacupuncture + LPS ( group SEL ) . At 6 h after LPS administration , the animals were sacrificed and the blood sample s were collected for biochemical measurements . The lungs were removed for calculation of wet-to-dry weight ratios ( W/D ) , histopathologic examination , determination of heme oxygenase (HO)-1 protein and mRNA , Nrf2 total and nucleoprotein , as well as Nrf2 mRNA expression , and evaluation of the intracellular distribution of Nrf2 nucleoprotein . LPS caused extensive morphologic lung damage , which was lessened by electroacupuncture treatment . Besides , lung W/D ratios were significantly decreased , the level of malondialdehyde was inhibited , plasma levels of TNF-α and interleukin-6 were decreased , while the activities of superoxide dismutase , glutathione peroxidase and catalase were enhanced in the electroacupucnture treated animals . In addition , electroacupuncture stimulation distinctly increased the expressions of HO-1 and Nrf2 protein including Nrf2 total protein and nucleoprotein as well as mRNA in lung tissue , while these effects were blunted in the sham electroacupuncture group . We concluded that electroacupuncture treatment at ST36 and BL13 effectively attenuates lung injury in a rabbit model of endotoxic shock through activation of Nrf2/ARE pathway and following up-regulation of HO-1 expression Background The anti-oxidative and anti-inflammatory activities of electro-acupuncture ( EA ) , a traditional clinical method , are widely accepted , but its mechanisms are not yet well defined . In this study , we investigated the role of extracellular signal-regulated kinases1/2 ( ERK1/2 ) pathways on electro-acupuncture – mediated up-regulation of heme oxygenase-1 ( HO-1 ) in rabbit lungs injured by LPS-induced endotoxic shock . Material / Methods Seventy rabbits were r and omly divided into 7 groups : group C , group M , group D , group SEAM , group EAM , group EAMPD , and group PD98059 .  Male New Engl and white rabbits were given EA treatment on both sides once a day on days 1–5 , and then received LPS to replicate the experimental model of injured lung induced by endotoxic shock . Then , they were killed by exsanguination at 6 h after LPS administration . The blood sample s were collected for serum examination , and the lungs were removed for pathology examination , determination of wet-to-dry weight ratio , MDA content , SOD activity , serum tumor necrosis factor-α , determination of HO-1 protein and mRNA expression , and determination of ERK1/2 protein . Results The results revealed that after EA  treatment , expression of HO-1 and ERK1/2 was slightly increased compared to those in other groups , accompanied with less severe lung injury as indicated by lower index of lung injury score , lower wet-to-dry weight ratio , MDA content , and serum tumor necrosis factor-α levels , and greater SOD activity ( p<0.05 for all ) . After pretreatment with ERK1/2 inhibitor PD98059 , the effect of EA treatment and expression of HO-1 were suppressed ( p<0.05 for all ) . Conclusions After electro-acupuncture stimulation at ST36 and BL13 , severe lung injury during endotoxic shock was attenuated . The mechanism may be through up-regulation of HO-1 , mediated by the signal transductions of ERK1/2 pathways . Thus , the regulation of ERK1/2 pathways via electro-acupuncture may be a therapeutic strategy for endotoxic shock Although systematic studies have demonstrated that acupuncture or electroacupuncture ( EA ) analgesia is based on their accelerating endogenous opioid release to activate opioid receptors and that EA of different frequencies is mediated by different opioid receptors in specific areas of the central nervous system , there is little direct , real-time evidence to confirm this in vivo . The present study was design ed to investigate the effects of transcutaneous electrical acupoint stimulation ( TEAS ) , an analogue of EA , at low and high frequencies on μ-opioid receptor ( MOR ) availability in the brain of rhesus monkeys . Monkeys underwent 95-min positron emission tomography ( PET ) with ( 11 ) C-carfentanil three times r and omly while receiving 0 , 2 , or 100 Hz TEAS , respectively . Each TEAS was administered in the middle 30 min during the 95-min PET scan , and each session of PET and TEAS was separated by at least 2 weeks . The results revealed that 2 Hz but not 100 Hz TEAS evoked a significant increase in MOR binding potential in the anterior cingulate cortex , the cau date nucleus , the putamen , the temporal lobe , the somatosensory cortex , and the amygdala compared with 0 Hz TEAS . The effect remained after the end of TEAS in the anterior cingulate cortex and the temporal lobe . The selective increase in MOR availability in multiple brain regions related to pain and sensory processes may play a role in mediating low-frequency TEAS efficacy Heme oxygenase (HO)-1 has been reported to play a great role in attenuating lung injury during endotoxic shock in our previous research . Although electro-acupuncture has been explored to reduce oxidative stress and decrease inflammatory reaction in animals with endotoxic shock , the mechanism of this effect is still unclear . The aim of this study was to determine whether HO-1 is involved in the effect of electro-acupuncture on the injured lung during endotoxic shock in rabbits . Sixty New Engl and white rabbits were r and omly divided into groups C , Z , ES , EA , AP , and EAZ . Before inducing endotoxic shock , group ES received no electro-acupuncture , while group EA received electro-acupuncture at ST36 ( zusanli ) and BL13 ( feishu ) acupoints on both sides for five days and group AP received electro-acupuncture ( EA ) stimulation at a non-acupoint . Groups ES , AP , EA , and EAZ received LPS to replicate the experimental model of injured lung induced by endotoxic shock , and electro-acupuncture was performed throughout the procedure with the same parameter . Groups EAZ and Z received the HO-1 inhibitor , ZnPP-IX , intraperitoneally . The animals were sacrificed by blood-letting at 6 h after LPS administration . The blood sample s were collected for serum examination , and the lungs were removed for pathology examination , detection of alveolaer epithelial cell apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay ( TUNEL assay ) , determination of wet to dry ratio , 
    Output:
    