Objective To investigate whether meranzin hydrate(MH)can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder(CSP),and further explore the potential common mechanisms.Methods Totally 120...Objective To investigate whether meranzin hydrate(MH)can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder(CSP),and further explore the potential common mechanisms.Methods Totally 120 Spraque-Dawley rats were randomly divided into 5–8 groups including sham,vehicle,fluoxetine(20 mg/kg),mosapride(10 mg/kg),CSP(30 g/kg),MH(9.18 mg/kg),[D-Lys3]-GHRP-6(Dlys,0.5 mg/kg),and MH+Dlys groups by a random number table,8 rats in each group.And 32 mice were randomly divided into wild-type,MH(18 mg/kg),growth hormone secretagogue receptor-knockout(GHSR-KO),and GHSR+MH groups,8 mice in each group.The forced swimming test(FST),open field test(OFT),tail suspension test(TST),gastric emptying(GE)test,and intestinal transit(IT)test were used to assess antidepressant and prokinetic(AP)effects after drug single administration for 30 min with absorbable identification in rats and mice,respectively.The protein expression levels of brain-derived neurotrophic factor(BDNF)and phosphorylated mammalian target of rapamycin(p-mTOR)in the hippocampus of rats were evaluated by Western blot.The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent(fMRI-BOLD).Results MH treatment improved depression-like behavior(FST,OFT)and hypomotility(GE,IT)in the acute forced swimming(FS)rats(all P<0.05),and the effects are similar to the parent formula CSP.The ghrelin antagonist[D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE(P<0.05).Similarly,MH treatment also alleviated depression-like behavior(FST,TST)in the wild-type mice,however,no effects were found in the GHSR KO mice.Additionally,administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus(both P<0.01),which were also prevented by[D-Lys3]-GHRP-6(P<0.01).Besides,3 main BOLD foci following acute FS rats implicated activity in hippocampus—thalamus—basal ganglia(HTB)circuits.The[D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci.As expected,prokinetic mosapride only had effects on the thalamus and basal ganglia,but not on the hippocampus.Within the HTB,the hippocampus is implicated in depression and FD.Conclusions MH accounts for part of AP effects of parent formula CSP in acute FS rats,mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas.This novel functionally connection of HTB following acute stress,treatment,and regulation highlights anti-depression unified theory.展开更多
BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impe...BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.展开更多
基金Supported by National Natural Science Foundation of China(No.81573797,81973589,and 81072967)the Priority Academic Program Development of Jiangsu Higher Education Institutions(Integration of Chinese and Western Medicine)。
文摘Objective To investigate whether meranzin hydrate(MH)can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder(CSP),and further explore the potential common mechanisms.Methods Totally 120 Spraque-Dawley rats were randomly divided into 5–8 groups including sham,vehicle,fluoxetine(20 mg/kg),mosapride(10 mg/kg),CSP(30 g/kg),MH(9.18 mg/kg),[D-Lys3]-GHRP-6(Dlys,0.5 mg/kg),and MH+Dlys groups by a random number table,8 rats in each group.And 32 mice were randomly divided into wild-type,MH(18 mg/kg),growth hormone secretagogue receptor-knockout(GHSR-KO),and GHSR+MH groups,8 mice in each group.The forced swimming test(FST),open field test(OFT),tail suspension test(TST),gastric emptying(GE)test,and intestinal transit(IT)test were used to assess antidepressant and prokinetic(AP)effects after drug single administration for 30 min with absorbable identification in rats and mice,respectively.The protein expression levels of brain-derived neurotrophic factor(BDNF)and phosphorylated mammalian target of rapamycin(p-mTOR)in the hippocampus of rats were evaluated by Western blot.The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent(fMRI-BOLD).Results MH treatment improved depression-like behavior(FST,OFT)and hypomotility(GE,IT)in the acute forced swimming(FS)rats(all P<0.05),and the effects are similar to the parent formula CSP.The ghrelin antagonist[D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE(P<0.05).Similarly,MH treatment also alleviated depression-like behavior(FST,TST)in the wild-type mice,however,no effects were found in the GHSR KO mice.Additionally,administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus(both P<0.01),which were also prevented by[D-Lys3]-GHRP-6(P<0.01).Besides,3 main BOLD foci following acute FS rats implicated activity in hippocampus—thalamus—basal ganglia(HTB)circuits.The[D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci.As expected,prokinetic mosapride only had effects on the thalamus and basal ganglia,but not on the hippocampus.Within the HTB,the hippocampus is implicated in depression and FD.Conclusions MH accounts for part of AP effects of parent formula CSP in acute FS rats,mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas.This novel functionally connection of HTB following acute stress,treatment,and regulation highlights anti-depression unified theory.
文摘BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.
