OBJECTIVE To investigate the levels of high-mobility group box 1(HMGB1)protein,soluble fms-like tyrosine kinase 1(sFLT-1)and lactate-to-albumin ratio(LAR)in patients with severe pulmonary infection-associ-ated sepsis undergoing continuous renal replacement therapy(CRRT),and their correlation with 28-day clinical outcomes.METHODS A total of 102 patients with severe pulmonary infection-associated sepsis undergoing CRRT admitted to the People's Hospital of Nanchuan Chongqing from Jul.2021 to Jul.2024 were enrolled.Based on 28-day clinical outcomes,they were divided into a favorable prognosis group(71 cases)and a poor prognosis group(31 cases).The levels of HMGB1,sFLT-1,lactate,albumin and LAR were compared between the two groups.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of HMGB1,sFLT-1 and LAR for 28-day clinical outcomes in patients with severe pulmonary infection-associated sepsis undergoing CRRT.RESULTS Gram-negative bacteria were the predominant pathogens in patients with se-vere pulmonary infection-associated sepsis undergoing CRRT.The poor prognosis group had higher lactate levels(4.01±1.07 mmol/L)and lower albumin levels(27.46±4.15 g/L)than the favorable prognosis group(P＜0.05).The levels of HMGB1(62.66±15.66 ng/ml),sFLT-1(0.71±0.17 ng/ml)and LAR(14.59±3.64％)in the poor prognosis group were significantly higher than those in the favorable prognosis group(P＜0.05).The combined detection of HMGB1,sFLT-1 and LAR yielded an area under the curve(AUC)of 0.949 for predicting poor 28-day mortality in patients with severe pulmonary infection-associated sepsis undergoing CRRT,superior to the single detection of the indexes(P＜0.05),with a sensitivity of 93.55％and specificity of 87.32％.CONCLUSIONS In patients with severe pulmonary infection-associated sepsis undergoing CRRT,gram-negative bacteria are the predominant pathogens.Patients with poor prognosis exhibit abnormally elevated levels of HMGB1,sFLT-1 and LAR,and the combined detection of these three markers demonstrates high predictive value for 28-day mortality.

OBJECTIVE To evaluate the efficacy and mechanism of Kai-Xin-San in improving intestinal function damage in-duced by intragastric administration of fluoxetine in chronic unpredictable mild stress(CUMS)depression model mice.METHODS A CUMS depression mouse model was established and treated with fluoxetine(9 mg·kg-1·d-1),low-dose(1.5 g·kg-1·d-1)and high-dose(4.5 g·kg-1·d-1)Kai-Xin-San,fluoxetine combined with low-dose(9 mg·kg-1·d-1+1.5 g·kg-1·d-1)and high-dose(9 mg·kg-1·d-1+4.5 g·kg-1·d-1)Kai-Xin-San,and mosapride combined with fluoxetine(2 mg·kg-1·d-1+9 mg·kg-1·d-1)for 28 consecutive days.The body weight of mice was measured;the food utilization was calculated and the serum D-xylose content was measured to evaluate the intestinal mucosal absorption capacity of mice;HE staining was used to evaluate the intestinal structural dam-age of mice;TUNEL staining was used to evaluate the intestinal tissue apoptosis of mice;ELISA was used to detect the expression lev-els of brain gut peptides such as vasoactive intestinal peptide(VIP),gastrin(MTL),substance P(SP)and Ghrelin in the intestine of mice;Western blot was used to detect the expression of apoptosis signaling pathway proteins.RESULTS Compared with the model group,fluoxetine significantly reduced the body weight of mice after 2 weeks of administration(P<0.05);the food utilization and ser-um D-xylose content of mice were significantly reduced after 4 weeks of administration(P<0.05),and the intestinal villi of depressed mice were damaged(P<0.05)and intestinal epithelial apoptosis of mice was enhanced(P<0.01);the expression of VIP in the small intestine of mice was upregulated(P<0.05),and the expression of MTL,SP and Ghrelin was downregulated(P<0.05,P<0.01);cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9 in the intestinal apoptosis signaling pathway of mice were upregulat-ed(P<0.05,P<0.01).Compared with the fluoxetine group,the body weight of mice was significantly increased after 2 weeks of com-bined use of Kai-Xin-San and fluoxetine(P<0.05,P<0.01).After 4 weeks of combined use of high-dose Kai-Xin-San and fluoxe-tine,the food utilization and serum D-xylose expression of mice were significantly increased(P<0.05);intestinal villus damage was improved(P<0.05);intestinal epithelial tissue apoptosis was significantly reduced(P<0.01);small intestinal VIP expression was significantly downregulated(P<0.01),and the expression of MTL,SP and Ghrelin was significantly upregulated(P<0.05);cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9 in the apoptosis signaling pathway were significantly reduced(P<0.05,P<0.01).CONCLUSION Kai-Xin-San has the effect of improving the gastrointestinal motility and intestinal absorption function dam-age caused by fluoxetine in depressed mice.Its mechanism may be related to improving the expression of brain gut peptide in the small intestine and inhibiting intestinal villi damage and intestinal tissue apoptosis.

Objective To evaluate the effect of Kaixin San(KXS)combined with fluoxetine on hippocampal neural stem cells in mice with chronic stress stress and depression.Methods A mouse model of depression was constructed using the method of chronic unpredictable stress stress,and the highest dose of KXS water extract and fluoxetine for clinical application was given for 28 days,and behavioral tests were carried out.Nissl staining was used to detect the pathological status of hippocampal tissues in mice.The expression of TUNEL and Nestin in mouse hippocampus was determined by immunofluorescence.Western blotting was used to detect the expressions of apoptotic proteins cleaved caspase-3 and caspase-3,pyroptosis proteins GSDMD and cleaved caspase-1,as well as the expression of neural stem cell marker Nestin in the hippocampus,and the expression of Wnt/β-catenin signaling pathway-related proteins in the hippocampus.Results The combination of KXS extract and fluoxetine can significantly improve the depression-like behavior of model mice,and the effect is better than fluoxetine alone.The combination inhibited the activation of apoptosis and pyroptosis signaling pathways in the hippocampus when used alone with high-dose fluoxetine,significantly upregulated the expression of Nestin,and regulated the expression of Wnt/β-catenin signaling pathway protein.Conclusion The combination of KXS and high-dose fluoxetine can improve apoptosis and pyroptosis in the hippocampus of stress stress and depression model mice,and upregulate the expression of neural stem cell marker Nestin by regulating the Wnt/β-catenin signaling pathway,which may be a key link to improve the antidepressant effect of the combination drug.

Objective Evaluate the effects of different solvent extracts from Jujing Pills on improving retinal damage in kidney Yang deficiency aging mice and explore the underlying mechanism.Methods A composite modeling method of subcutaneous injection of D-galactose and hind limb injection of hydrocortisone was used to establish a kidney Yang deficiency type aging mouse model,and various solvent extract of Jujing Pills were given for intervention treatment.The improvement effect of different solvent extracts of Jujing Pills on aging mice with kidney Yang deficiency was evaluated by observing physical signs,measuring serum oxidative stress marker levels,and cyclic nucleotide levels.Optical coherence tomography(OCT)was used to detect the condition of the mouse retina,HE staining was used to detect the degree of retinal cell damage,TUNEL staining was used to detect retinal cell apoptosis,assay kit was used to detect oxidative stress factor expression,enzyme-linked immunosorbent assay was used to detect the expression of ciliary neurotrophic factor(CNTF),brain-derived neurotrophic factor(BDNF),and nerve growth factor(NGF)in the mouse eyeball,and Western blotting(WB)was used to quantitatively analyze the expression levels of apoptosis and neurotrophic pathway related proteins in the mouse retina tissue.Results Compared with the control group,the model group mice showed slow weight gain,reduced activity,decreased expression of antioxidant factors such as superoxide dismutase(SOD)and glutathione(GSH)in serum(P<0.01),and decreased cAMP/cGMP ratio(P<0.01).Different solvent extracts of Jujing Pills significantly increased the expression of antioxidant factors such as SOD and GSH(P<0.05),reduced the production of oxidative product malondialdehyde(MDA)(P<0.01),and increased the cAMP/cGMP ratio(P<0.01);Significantly increased the retinal thickness of model mice(P<0.01),improved retinal damage and inhibited retinal cell apoptosis(P<0.01),and significantly downregulated the ratio expression levels of Cleaved Caspase-3 and Caspase-3(P<0.01);The expression of CNTF,BDNF,and NGF was upregulated by water extracted medicinal residue alcohol extract,water extracted alcohol sediment,and total extract(P<0.01).The phosphorylation levels of CREB and ERK in the eyeball were significantly upregulated by water extracted medicinal residue alcohol extract and total extract(P<0.05).Conclusion Different solvent extracts of Jujing Pills can exert different pharmacological effects on improving retinal damage in aging mice with kidney yang deficiency model.Its mechanism of action is related to improving retinal apoptosis caused by oxidative stress and increasing the expression of nutritional factors.

OBJECTIVE To evaluate the efficacy and mechanism of Kai-Xin-San in improving intestinal function damage in-duced by intragastric administration of fluoxetine in chronic unpredictable mild stress(CUMS)depression model mice.METHODS A CUMS depression mouse model was established and treated with fluoxetine(9 mg·kg-1·d-1),low-dose(1.5 g·kg-1·d-1)and high-dose(4.5 g·kg-1·d-1)Kai-Xin-San,fluoxetine combined with low-dose(9 mg·kg-1·d-1+1.5 g·kg-1·d-1)and high-dose(9 mg·kg-1·d-1+4.5 g·kg-1·d-1)Kai-Xin-San,and mosapride combined with fluoxetine(2 mg·kg-1·d-1+9 mg·kg-1·d-1)for 28 consecutive days.The body weight of mice was measured;the food utilization was calculated and the serum D-xylose content was measured to evaluate the intestinal mucosal absorption capacity of mice;HE staining was used to evaluate the intestinal structural dam-age of mice;TUNEL staining was used to evaluate the intestinal tissue apoptosis of mice;ELISA was used to detect the expression lev-els of brain gut peptides such as vasoactive intestinal peptide(VIP),gastrin(MTL),substance P(SP)and Ghrelin in the intestine of mice;Western blot was used to detect the expression of apoptosis signaling pathway proteins.RESULTS Compared with the model group,fluoxetine significantly reduced the body weight of mice after 2 weeks of administration(P<0.05);the food utilization and ser-um D-xylose content of mice were significantly reduced after 4 weeks of administration(P<0.05),and the intestinal villi of depressed mice were damaged(P<0.05)and intestinal epithelial apoptosis of mice was enhanced(P<0.01);the expression of VIP in the small intestine of mice was upregulated(P<0.05),and the expression of MTL,SP and Ghrelin was downregulated(P<0.05,P<0.01);cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9 in the intestinal apoptosis signaling pathway of mice were upregulat-ed(P<0.05,P<0.01).Compared with the fluoxetine group,the body weight of mice was significantly increased after 2 weeks of com-bined use of Kai-Xin-San and fluoxetine(P<0.05,P<0.01).After 4 weeks of combined use of high-dose Kai-Xin-San and fluoxe-tine,the food utilization and serum D-xylose expression of mice were significantly increased(P<0.05);intestinal villus damage was improved(P<0.05);intestinal epithelial tissue apoptosis was significantly reduced(P<0.01);small intestinal VIP expression was significantly downregulated(P<0.01),and the expression of MTL,SP and Ghrelin was significantly upregulated(P<0.05);cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9 in the apoptosis signaling pathway were significantly reduced(P<0.05,P<0.01).CONCLUSION Kai-Xin-San has the effect of improving the gastrointestinal motility and intestinal absorption function dam-age caused by fluoxetine in depressed mice.Its mechanism may be related to improving the expression of brain gut peptide in the small intestine and inhibiting intestinal villi damage and intestinal tissue apoptosis.

OBJECTIVE To investigate the levels of high-mobility group box 1(HMGB1)protein,soluble fms-like tyrosine kinase 1(sFLT-1)and lactate-to-albumin ratio(LAR)in patients with severe pulmonary infection-associ-ated sepsis undergoing continuous renal replacement therapy(CRRT),and their correlation with 28-day clinical outcomes.METHODS A total of 102 patients with severe pulmonary infection-associated sepsis undergoing CRRT admitted to the People's Hospital of Nanchuan Chongqing from Jul.2021 to Jul.2024 were enrolled.Based on 28-day clinical outcomes,they were divided into a favorable prognosis group(71 cases)and a poor prognosis group(31 cases).The levels of HMGB1,sFLT-1,lactate,albumin and LAR were compared between the two groups.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of HMGB1,sFLT-1 and LAR for 28-day clinical outcomes in patients with severe pulmonary infection-associated sepsis undergoing CRRT.RESULTS Gram-negative bacteria were the predominant pathogens in patients with se-vere pulmonary infection-associated sepsis undergoing CRRT.The poor prognosis group had higher lactate levels(4.01±1.07 mmol/L)and lower albumin levels(27.46±4.15 g/L)than the favorable prognosis group(P＜0.05).The levels of HMGB1(62.66±15.66 ng/ml),sFLT-1(0.71±0.17 ng/ml)and LAR(14.59±3.64％)in the poor prognosis group were significantly higher than those in the favorable prognosis group(P＜0.05).The combined detection of HMGB1,sFLT-1 and LAR yielded an area under the curve(AUC)of 0.949 for predicting poor 28-day mortality in patients with severe pulmonary infection-associated sepsis undergoing CRRT,superior to the single detection of the indexes(P＜0.05),with a sensitivity of 93.55％and specificity of 87.32％.CONCLUSIONS In patients with severe pulmonary infection-associated sepsis undergoing CRRT,gram-negative bacteria are the predominant pathogens.Patients with poor prognosis exhibit abnormally elevated levels of HMGB1,sFLT-1 and LAR,and the combined detection of these three markers demonstrates high predictive value for 28-day mortality.

Objective To evaluate the effect of Kaixin San(KXS)combined with fluoxetine on hippocampal neural stem cells in mice with chronic stress stress and depression.Methods A mouse model of depression was constructed using the method of chronic unpredictable stress stress,and the highest dose of KXS water extract and fluoxetine for clinical application was given for 28 days,and behavioral tests were carried out.Nissl staining was used to detect the pathological status of hippocampal tissues in mice.The expression of TUNEL and Nestin in mouse hippocampus was determined by immunofluorescence.Western blotting was used to detect the expressions of apoptotic proteins cleaved caspase-3 and caspase-3,pyroptosis proteins GSDMD and cleaved caspase-1,as well as the expression of neural stem cell marker Nestin in the hippocampus,and the expression of Wnt/β-catenin signaling pathway-related proteins in the hippocampus.Results The combination of KXS extract and fluoxetine can significantly improve the depression-like behavior of model mice,and the effect is better than fluoxetine alone.The combination inhibited the activation of apoptosis and pyroptosis signaling pathways in the hippocampus when used alone with high-dose fluoxetine,significantly upregulated the expression of Nestin,and regulated the expression of Wnt/β-catenin signaling pathway protein.Conclusion The combination of KXS and high-dose fluoxetine can improve apoptosis and pyroptosis in the hippocampus of stress stress and depression model mice,and upregulate the expression of neural stem cell marker Nestin by regulating the Wnt/β-catenin signaling pathway,which may be a key link to improve the antidepressant effect of the combination drug.

Objective Evaluate the effects of different solvent extracts from Jujing Pills on improving retinal damage in kidney Yang deficiency aging mice and explore the underlying mechanism.Methods A composite modeling method of subcutaneous injection of D-galactose and hind limb injection of hydrocortisone was used to establish a kidney Yang deficiency type aging mouse model,and various solvent extract of Jujing Pills were given for intervention treatment.The improvement effect of different solvent extracts of Jujing Pills on aging mice with kidney Yang deficiency was evaluated by observing physical signs,measuring serum oxidative stress marker levels,and cyclic nucleotide levels.Optical coherence tomography(OCT)was used to detect the condition of the mouse retina,HE staining was used to detect the degree of retinal cell damage,TUNEL staining was used to detect retinal cell apoptosis,assay kit was used to detect oxidative stress factor expression,enzyme-linked immunosorbent assay was used to detect the expression of ciliary neurotrophic factor(CNTF),brain-derived neurotrophic factor(BDNF),and nerve growth factor(NGF)in the mouse eyeball,and Western blotting(WB)was used to quantitatively analyze the expression levels of apoptosis and neurotrophic pathway related proteins in the mouse retina tissue.Results Compared with the control group,the model group mice showed slow weight gain,reduced activity,decreased expression of antioxidant factors such as superoxide dismutase(SOD)and glutathione(GSH)in serum(P<0.01),and decreased cAMP/cGMP ratio(P<0.01).Different solvent extracts of Jujing Pills significantly increased the expression of antioxidant factors such as SOD and GSH(P<0.05),reduced the production of oxidative product malondialdehyde(MDA)(P<0.01),and increased the cAMP/cGMP ratio(P<0.01);Significantly increased the retinal thickness of model mice(P<0.01),improved retinal damage and inhibited retinal cell apoptosis(P<0.01),and significantly downregulated the ratio expression levels of Cleaved Caspase-3 and Caspase-3(P<0.01);The expression of CNTF,BDNF,and NGF was upregulated by water extracted medicinal residue alcohol extract,water extracted alcohol sediment,and total extract(P<0.01).The phosphorylation levels of CREB and ERK in the eyeball were significantly upregulated by water extracted medicinal residue alcohol extract and total extract(P<0.05).Conclusion Different solvent extracts of Jujing Pills can exert different pharmacological effects on improving retinal damage in aging mice with kidney yang deficiency model.Its mechanism of action is related to improving retinal apoptosis caused by oxidative stress and increasing the expression of nutritional factors.

Objective To explore the anti-depression mechanism of Kai-Xin-San(KXS)via regulation of neurogenesis in hippocampus of depression-like mice.Methods The extracts of KXS were prepared and the anti-depression effects of KXS were evaluated by behavioral tests on chronic unpredictable mild stress(CUMS)induced depression-like mice.Evaluating depression-like behavior in CUMS mice through sucrose preference test,forced swimming test,tail suspension test,and other methods.Neurogenesis in hippocampus were determined by immunofluorescence assay.In addition,effects of KXS on regulating nestin expression and Wnt/b-catenin signaling pathway were explored by western blotting analysis.Amounts of cortisol,corticotropin-releasing factor(CRF),adrenocorticotropic hormone(ACTH),brain-derived neurotrophic factor(BDNF)and nerve growth factor(NGF)were determined by ELISA tests.Mouse primary neural stem cells(NSC)was used to evaluate the effect of KXS on promoting its proliferation by immunofluorescence assay.In addition,effects of KXS on regulating nestin and Wnt/β-catenin signaling pathway were also explored by Western blotting analysis.Results KXS significantly ameliorated the depression-like behaviors in presence of increased sucrose preference rate and decreased immobile time of tail suspension and forced swimming.KXS significantly promoted the neurogenesis in the hippocampus and expressions of nestin,reduced the expressions of cortisol,CRF,ACTH,increased the expressions of BDNF,NGF,and regulated Wnt/β-catenin signaling pathway.KXS also promoted the proliferation of NSCs and expressions of nestin,enhanced the translocation of b-catenin into nucleus,and regulated the expressions of proteins of Wnt/β-catenin signaling pathway.Conclusion KXS promoted neurogenesis in hippocampus and regulated Wnt/β-catenin pathway,which might contribute to its antidepressant effect.

Objective To investigate the beneficial effect of Kai-Xin-San combined with fluoxetine in improving depression-like behaviors on chronic unpredictable mild stress(CUMS)induced depression model mice.Methods The present study aimed to assess the potential of Kai-Xin-San in combination with fluoxetine to ameliorate depression-like behaviors in a CUMS induced mouse depression model.Behavioral tests,such as the sucrose preference test were employed to evaluate the efficacy of the treatment.Additionally,the levels of suppressed stress factors were measured using the ELISA method.The morphology of hippocampal tissue was evaluated using the HE staining method,Nissl Staining and TUNEL staining methods.Furthermore,western blotting analysis was utilized to determine the expression levels of proteins such as Caspase-3,and Caspase-9.Results The co-administration of Kai-Xin-San and fluoxetine resulted in a significant increase in sucrose preference rate in model mice.This effect was comparable to that of fluoxetine alone at the standard clinical dose.Furthermore,the combination treatment up-regulated the levels of suppressed stress factors,reduced the apoptosis of hippocampus induced by depression and regulated the apoptosis signaling pathway in hippocampus.Conclusion The combination of Kai-Xin-San and fluoxetine has been shown to be an effective treatment for depression-like behavior in animal models,resulting in a reduction in the required clinical dosage of fluoxetine.This effect may be attributed to the up-regulation of neurotransmitter expression,inhibition of stress axis activation,and central nervous inflammation.