Chronic liver diseases with common causes including viral infections， alcohol abuse， and autoimmune diseases. Alkaloids， as a class of plant-derived compounds， have shown significant potential in regulating chronic liver diseases. Recent studies have shown that alkaloids are able to exert a therapeutic effect on chronic liver diseases through multiple pathways. These compounds have a regulatory effect on key pathological processes such as liver fibrosis， inflammatory response， oxidative stress， and cell apoptosis， and they also regulate the metabolic homeostasis of hepatocytes by modulating multiple signaling pathways， thereby playing a role in regulating chronic liver diseases. This article reviews the role and mechanism of alkaloids in the treatment of chronic liver diseases， in order to provide new ideas and directions for the treatment of chronic liver diseases.

The construction of a new cultural system for high-quality development in public hospitals serves as a crucial pillar for achieving their high-quality advancement.During this developmental processe stablishing a cultural framework that aligns with the new development model holds particular significance.Through content analysis methodology,it identifies 18 core elements of the new cultural system for high-quality development in public hospitals.Furthermore it synthesizes seven implementation pathways across three dimensions-organizational patientand employee perspectives:digital leadership organizational reform capability talent innovation capability resource integration capability normative constraint force value co-creation capability and employee support capability.These findings provide both theoretical and practical references for cultivating new cultural constructs that facilitate high-quality development in public hospitals.

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 mechanism of action of curcumol on mitochondrial autophagy in hepatic stellate cells and its molecular mechanism against liver fibrosis. Methods : Hepatic stellate cells were divided into blank group, model group(lipopolysaccharide 5 mg/L), and low, medium and high curcumol group(12.5, 25 and 50 mg/L); Thiazolyland(MTT) was used to detect the effects of curcumol on the viability of hepatic stellate cells; flow cytometry was used to detect the effects of curcumol on apoptosis of hepatic stellate cells; 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylimidacarbocyanine iodide(JC-1) was used to detect the mitochondrial membrane potential; effects of curcumol on mitochondrial morphology and autophagosome were detected by transmission electron microscopy; effect of curcumol on mitochondrial localisation were detected by fluorescent probe; Immunoblotting assay was performed to detect the effects of curcumin on PTEN-induced putative kinase 1(PINK1), Parkinson's disease protein(Parkin), microtubule-associated protein light chain 3(LC3), autophagy-associated protein(Beclin1), mitochondrial inner membrane translocase 23(Timm23), mitochondrial outer membrane translocase 20(Tomm20), Bcl-2 associated X protein(Bax), B lymphocytoma-2(Bcl2), cleaved-cysteine protease 3(Caspase3), α-smooth muscle actin(ɑ-SMA), collagen type Ⅰ(Collagen Ⅰ), and collagen type Ⅲ(Collagen Ⅲ) protein expression. Results : Compared with the blank control group, cell proliferation rate, Caspase3, Bcl2, LC3Ⅱ, Beclin1, PINK1, Parkin, ɑ-SMA, CollagenⅠ, CollagenⅢ proteins significantly increased in the model group(P<0.01), co-localisation of mitochondria and lysosomes increased, and the number of mitochondrial autophagosome significantly increased(P<0.01), while Timm23 and Tomm20 proteins, mitochondrial membrane potential decreased significantly(P<0.01), apoptosis rate decreased, and Bax protein expression decreased. Compared with the model group, after curcumol intervention, cell proliferation rate, Bcl2, Timm23, Tomm20, α-SMA, CollagenⅠ and CollagenⅢ protein expression significantly decreased in the curcumol low-, medium-and high-concentration groups(P<0.01), and the mitochondrial membrane potential significantly decreased(P<0.01), whereas apoptosis rate, Caspase3, Bax, LC3Ⅱ, Beclin1, PINK1 and Parkin proteins significantly increased(P<0.05), the co-localisation of mitochondria and lysosomes increased, and the number of mitochondrial autophagosome significantly increased(P<0.01). Conclusion Curcumol exerts ameliorative effects on hepatic fibrosis by modulating mitochondrial hyperautophagy mediated by the PINK1/Parkin signaling pathway, and promoting hepatic stellate cell apoptosis.

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.

The construction of a new cultural system for high-quality development in public hospitals serves as a crucial pillar for achieving their high-quality advancement.During this developmental processe stablishing a cultural framework that aligns with the new development model holds particular significance.Through content analysis methodology,it identifies 18 core elements of the new cultural system for high-quality development in public hospitals.Furthermore it synthesizes seven implementation pathways across three dimensions-organizational patientand employee perspectives:digital leadership organizational reform capability talent innovation capability resource integration capability normative constraint force value co-creation capability and employee support capability.These findings provide both theoretical and practical references for cultivating new cultural constructs that facilitate high-quality development in public hospitals.

Chronic liver disease(CLD)tends to have a high incidence rate and impose a serious burden on society and families.Studies have shown that metal ion metabolism is closely associated with CLD,and some Chinese herbal medicines can play a role in the prevention and treatment of CLD by regulating metal ion metabolism.At present,the synthetic drugs currently used for the treatment of CLD fail to achieve a satisfactory effect,and therefore,a variety of Chinese herbal medicines are being used as supplementary and alternative therapies for CLD.This article introduces the role of metal ion metabolism in CLD and the regulatory effect of Chinese herbal medicines and their active components on CLD,and the analysis shows that metal ion metabolism is expected to provide new ideas for the research on CLD and a theoretical basis for the clinical treatment of CLD.For the role of metal ion metabolism in the treatment of CLD,more prospective clinical study data are needed in the future to provide effective and safe treatment regimens for patients with CLD.

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.

BACKGROUND:In recent years,the development of liver organoids has made it a hot spot in the field of international liver disease research,but there is still no article on the bibliometric analysis of liver organoids. OBJECTIVE:To explore the hot trends in liver organoids in the last 20 years based on bibliometrics and visualization analysis. METHODS:We searched the articles about liver organoids in the Web of Science Core Collection from January 1,2002 to November 12,2022.Origin,Office,and CiteSpace software were used for bibliometrics and visualization analysis.We statistically analyzed the number of annually published articles,countries,institutions,authors,journals,and keywords of the articles by generating charts. RESULTS AND CONCLUSION:The number of articles,citation frequency,institutions and personnel involved in the research about liver organoids showed an overall upward trend in the last 20 years,indicating that the field was growing rapidly and attention was increasing.The USA had published the most papers and had the strongest influence in this field.Although it had invested a lot of time and energy,the number of papers published by a single research institution in the USA was not the highest among many research institutions.China was second only to the USA in the number of publications,with the Chinese Academy of Sciences and Fudan University leading the list.Utrecht University in the Netherlands was the institution with the most publications.Clevers H was the author with the highest number of articles.The article with the highest co-citation frequency was"Long-term culture of genome-stable bipotent stem cells from adult human liver".The main fields of study for liver organoids were Molecular Science,Biology,and Immunology.The most frequently occurring keywords were stem cell,in vitro,and culture.The research hotspots in the liver organoids field were mainly focused on in vitro stem cell three-dimensional culture,differentiation and gene expression.

OBJECTIVE To determine the effect of Kai-Xin-San(KXS)combined with fluoxetine on the intestinal flora and the expression of inflammatory factors in chronic unpredictable mild stress(CUMS)depression mice and to elucidate the antidepressant mechanism of regulating"intestine-brain"axis.METHODS CUMS depression mice model was established and the effect of com-bined medication on improving depression-like behaviors of mice was evaluated by determination of sucrose preference rate,immobile time of tail suspension and forced swimming.Additionally,the levels of inflammatory factors IL-6,IL-1β,TNF-α and LPS were de-termined in cortex,serum and intestine using the ELISA method.The composition of intestinal flora in mouse feces was analyzed by 16S rRNA sequence sequencing.Furthermore,Western blot assay was utilized to determine the expression levels of intestinal barrier proteins such as ZO-1,Occludin and Claudin-5.RESULTS The combination of KXS and fluoxetine resulted in a significant in-crease in sucrose preference rate(P<0.01)and decreased immobile time of tail suspension and forced swimming(P<0.05,P<0.01)in CUMS mice.The antidepressant effect of KXS combined with middle dose of fluoxetine was equivalent to that of high dose of fluoxe-tine alone.Meanwhile,the combination could significantly inhibit the up-regulation of inflammatory factors in the cortex,serum and small intestine of model animals(P<0.05,P<0.01).Intestinal flora analysis showed that the combination could improve the ratio of Gram-positive bacteria to negative bacteria in the intestinal tract of model animals,and the improvement of the relative abundance of intestinal bacteria Lachnospiraceae,Bifidobacterium,Ruminococcus,Blautia,Eubacterium,Intestinimonas,Erysipelotrichaceae,Alis-tipes,Desulfovibrionia and Coriobacteriaceae UCG-002 and so on in the model animals was significantly related to the alleviation of de-pression-like behavior and the down-regulation of cortical inflammatory factors(P<0.05,P<0.01).Furthermore,the combination treatment could significantly up-regulate the expression of intestinal barrier protein(P<0.01).CONCLUSION KXS combined with fluoxetine can alleviate depression-like behavior and reduce fluoxetine dosage in CUMS model animals.The combination of the two drugs may regulate the composition of intestinal flora,inhibit the expression of intestinal inflammatory factors,up-regulate intestinal barrier proteins,and thus reduce the expression of serum and central inflammatory factors,which may be the mechanism of their regu-lation of the gut brain axis in antidepressant action.