ObjectiveTo investigate the therapeutic effect and mechanism of Huatan Qushi Huoxue prescription on rats with metabolic dysfunction-associated steatohepatitis （MASH）. MethodsA total of 60 specific pathogen-free Sprague-Dawley rats were randomly divided into blank control group， model A group， model B group， Western medicine group （polyene phosphatidylcholine， 143.64 mg/kg）， high-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 20.16 g/kg）， and middle-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 10.08 g/kg）. All rats except those in the blank control group were given high-fat diet. Samples were collected from the model A group at week 8， and since week 12， the other groups were given the corresponding drug once a day for 8 consecutive weeks， with samples collected at week 20. Body weight， liver wet weight， and liver index were measured for all rats； the microplate method was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acids （FFA）； ELISA was used to measure the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and soluble triggering receptor expressed on myeloid cells 2 （sTREM2）； HE staining and oil red O staining were performed to observe liver histopathological changes； immunofluorescence assay was used to measure CD68⁺TREM2⁺ cells in liver tissue and calculate the phagocytosis rate of macrophages； quantitative real-time PCR was used to measure the mRNA expression levels of sphingosine 1-phosphate （S1P）， sphingosine 1-phosphate receptor 1 （S1PR1）， a disintegrin and metalloproteinase 17 （ADAM17）， and triggering receptor expressed on myeloid cells 2 （TREM2） in liver tissue， and immunohistochemistry was used to measure the protein expression levels of S1P， S1PR1， ADAM17， and TREM2 in liver tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between groups， and the least significant difference t-test was used for further comparison between two groups； the Welch’s test was used for comparison of normally distributed continuous data with heterogeneity of variance between groups， and the Tamhane’s test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the blank control group， the model A group and the model B group had significant increases in body weight and liver wet weight， and the model B group had a significant increase in liver index （all P<0.05）. HE staining showed diffuse macrovesicular steatosis of liver tissue in the model A group and a large number of hepatocytes with ballooning degeneration in liver tissue in the model group B， with the presence of mixed inflammatory cell infiltration and mild perisinusoidal fibrosis in the lobules and the portal area. Compared with the blank control group， the model A group and the model B group had significant increases in NAS score and oil red O-positive area （all P<0.05）， and the model B group had significant increases in these two indicators than the model A group （both P<0.05）. Compared with the blank control group， the model A group and the model B group had significant increases in the serum levels of TC， TG， LDL-C， FFA， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C， and the model B group had significant increases in the serum levels of ALT， AST， and TNF-α （all P<0.05）； compared with the model A group， the model B group had significant increases in the serum levels of ALT， AST， TC， TG， FFA， TNF-α， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C （all P<0.05）. Immunofluorescence assay showed that compared with the blank control group， the model A group had a significant increase in the phagocytosis rate of macrophages （P<0.05）， while the model B group had a significantly lower phagocytosis rate of macrophages than the model A group （P<0.05）. Quantitative real-time PCR showed that compared with the blank control group， the model A group and the model B group had a significant increase in the mRNA expression level of TREM2， and the model B group had significant increases in the mRNA expression levels of S1P and S1PR1 （both P<0.05）； moreover， compared with the model A group， the model B group had significant increases in the mRNA expression levels of S1PR1 and TREM2 （both P<0.05）. Immunohistochemistry showed that compared with the blank control group， the model A group and the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17， and the model A group had a significant increase in the protein expression level of TREM2 （all P<0.05）； compared with the model A group， the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17 and a significant reduction in the protein expression level of TREM2 （all P<0.05）. Compared with the model B group， each medication group had significant reductions in body weight， liver wet weight， and liver index （all P<0.05）； each medication group had significant improvements in hepatic steatosis and inflammatory damage， with significant reductions in NAS score and oil red O-positive area （all P<0.05）； each medication group had significant reductions in the serum levels of ALT， AST， TC， TG， FFA， IL-1β， and IL-6 （all P<0.05） and a significant increase in the serum level of HDL-C （P<0.05）， and the high-dose Chinese medicine group had a significant reduction in the serum level of TNF-α （P<0.05）； each medication group had a significant increase in the phagocytosis rate of macrophages （all P<0.05）； the high- and middle-dose Chinese medicine groups had a significant reduction in the protein expression level of ADAM17， and the high-dose Chinese medicine group had a significant increase in the protein expression level of TREM2 （all P<0.05）. ConclusionHuatan Qushi Huoxue prescription improves lipid metabolism and inflammation in the liver of MASH rats by regulating hepatic macrophage phagocytosis.

OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

Liver fibrosis is the core pathological stage of the progression of various chronic liver diseases to liver cirrhosis， and hepatic stellate cell （HSC） activation and the abnormal accumulation of collagen fibers are important processes for the development and progression of liver fibrosis. In recent years， studies have shown that HSC activation is regulated by the complex interactions between various organelles （including mitochondria， endoplasmic reticulum， Golgi apparatus， lysosome， and peroxisomes）， and such interactions affect the key cellular processes such as energy metabolism， protein synthesis and folding， reactive oxygen species balance， and autophagy， thereby participating in the progression of liver fibrosis. Meanwhile， traditional Chinese medicine and its active ingredients with multi-target synergistic effects have attracted wide attention. From the perspective of the interaction between organelles， this article systematically elaborates on the specific mechanism of such interactions in the progression of liver fibrosis and reviews how traditional Chinese medicine inhibits HSC activation and collagen production by regulating the function of these organelle and their interaction networks， thereby exerting an anti-liver fibrosis effect， in order to provide a theoretical basis for in-depth understanding of the pathological mechanism of liver fibrosis and the development of new traditional Chinese medicine intervention strategies.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is a chronic metabolic liver disorder with complex etiologies. Different clinical phenotypes of MAFLD （such as obesity， hyperlipidemia， type 2 diabetes mellitus， the postmenopausal state， and chronic hepatitis B） have different mechanisms of action in the development and progression of MAFLD， leading to high heterogeneity in its clinical progression and prognosis. This article systematically reviews the pathogeneses and clinical features of the above five clinical phenotypes of MAFLD and elaborates on the corresponding individualized diagnosis and treatment regimens integrating traditional Chinese medicine and Western medicine， in order to provide a reference for clinical practice and improve clinical diagnosis and treatment.

Metabolic associated fatty liver disease （MAFLD） is a chronic liver disease with a rapidly increasing incidence rate worldwide， and its complex pathogenesis is closely associated with O-linked β-N-acetylglucosamine （O-GlcNAc） modification. As a dynamic and reversible post-translational modification of proteins， O-GlcNAc modification is mainly regulated by O-GlcNAc transferase and O-GlcNAcase. O-GlcNAc modification can drive hepatic steatosis， exacerbate insulin resistance， and impair mitochondrial function， thereby leading to the aggravation of metabolic disorders， promoting inflammation response， and driving the progression of MAFLD to metabolic associated steatohepatitis and hepatic fibrosis. This article systematically reviews the latest research advances in the role of O-GlcNAc modification in the development and progression of MAFLD， in order to provide theoretical support and research direction for a deeper understanding of the pathological mechanism of MAFLD and the development of effective therapeutic strategies.

OBJECTIVE To investigate the mechanism of Yangfei tongluo formula in delaying airway remodeling in post-infectious bronchiolitis obliterans （PIBO） model rats.METHODS Forty-eight 2-week-old SPF male SD rats were randomly divided into control group （Control group）， PIBO model group （Model group）， Prednisone Acetate tablets+Azithromycin tablets group [positive control group， Prednisone Acetate tablets 0.006 3 g/（kg·d）+Azithromycin tablets 0.031 5 g/（kg·d）]， and high-， medium-， and low-dose Yangfei tongluo formula groups [42.42， 21.21， 10.60 g/（kg·d）]. The PIBO rat model was established by intratracheal instillation of diacetyl. After modeling， rats in each group were administered corresponding drug solution or distilled water by gavage once daily for 21 consecutive days. Hematoxylin-eosin staining was used to evaluate the pathological changes of lung tissue， and Masson staining was used to assess the degree of pulmonary fibrosis. Western blot and real-time quantitative PCR were performed to detect the protein and mRNA expression levels of epithelial-mesenchymal transition （EMT）-related markers [E-cadherin， N-cadherin， α -smooth muscle actin （ α -SMA）， Vimentin] and transcription factors [snail homolog 1（Drosophila）-like 1 protein （Snail1）， zinc finger E-box-binding homeobox protein 1 （ZEB1）， Twist-related protein 1 （Twist1）] in lung tissue. ELISA was used to detect the levels of transforming growth factor-β 1 （TGF-β 1 ） and vascular endothelial growth factor （VEGF） in blood and bronchoalveolar lavage fluid.RESULTS Compared with the Control group， the lung tissues of rats in the Model group showed extensive destruction of alveolar structure and massive inflammatory cell infiltration in the interstitium. The protein and mRNA expression levels of E-cadherin were significantly decreased， while the protein and mRNA expression levels of N-cadherin， Vimentin， α -SMA， Snail1， ZEB1， and Twist1， as well as the collagen-positive area and the levels of TGF-β 1 and VEGF， were significantly increased （ P ＜0.05）. Compared with the Model group， the pathological injury of lung tissue in each administration group was significantly improved， and the above indicators （except collagen-positive area） were significantly reversed （ P ＜0.05）.CONCLUSIONS Yangfei tongluo formula may delay airway remodeling in PIBO by regulating the TGF-β 1 /VEGF-mediated signaling network and inhibiting the activation of EMT-related transcription factors， thereby blocking the EMT process.

Nonalcoholic fatty liver disease（NAFLD） is the most common chronic liver disease in the world. Because of its complex pathogenesis， high clinical prevalence and large population， it poses a great threat and challenge to public health in the world. Therefore， active intervention measures are needed. Currently， western medicine is effective in reducing weight， reducing liver fat content， improving glucose-lipid metabolism and insulin resistance. However， for patients with NAFLD-related fibrosis and cirrhosis， there is still a lack of sufficient histological evidence to support its benefits， and randomized controlled trials are still needed to clarify. Lifestyle intervention is an important cornerstone for the treatment of NAFLD， but there are many problems such as poor implementation and low compliance of patients， and the clinical efficacy is not ideal. Traditional Chinese medicine（TCM） has the significant advantages of multiple pathways and multiple targets. Berberine， the active ingredient of TCM， can interfere with the production of NAFLD from multiple pathways， including increasing energy consumption， weight loss， improving glucose-lipid metabolism， improving insulin resistance， anti-inflammatory， anti-oxidation， regulating intestinal flora， restoring bile acid homeostasis， anti-fibrosis and so on， which can play a positive role in the treatment of NAFLD. At the same time， it was found that the combination of BBR with Chinese and western medicines had significant advantages in promoting drug absorption， improving oral bioavailability， increasing the highest biological distribution in the liver， enhancing the overall therapeutic effect of NAFLD， and reducing adverse drug reactions， which could provide reference for clinical medication.

ObjectiveTo investigate the association of menopausal time and menopausal age with the risk of nonalcoholic fatty liver disease （NAFLD）， and to provide a basis for the early prevention and treatment of NAFLD in clinical practice. MethodsRelated data were collected from 373 postmenopausal women who attended the outpatient service of Department of Spleen， Stomach， Liver and Gallbladder Diseases， The First Affiliated Hospital of Henan University of Chinese Medicine， from January 2017 to December 2021， including general information， menopausal age， menopausal time， and presence or absence of NAFLD. The chi-square test was used for comparison of categorical data； the independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups. A Logistic regression analysis was used to calculate the association intensity and 95% confidence interval （95%CI） of menopausal time and menopausal age for the risk of NAFLD， and the restricted cubic spline （RCS） method was used to investigate the dose-response relationship between menopausal time/age and the risk of NAFLD. ResultsCompared with the women with normal menopause or late menopause， the women with early menopause had a higher prevalence rate of NAFLD and a higher degree of steatosis and fibrosis （all P<0.05）. After adjustment for the confounding factors such as age and age of menarche， the risk of NAFLD in women with a menopausal time of >3 years was 4.80 （95%CI： 1.93‍ ‍—‍‍ ‍11.95， P=0.001） times that in women with a menopausal time of ≤3 years， and the risk of NAFLD in women with early or late menopause was 8.14 times （95%CI： ‍1.77 ‍— ‍37.58， P=0.007） and 0.09 times （95%CI： 0.03 ‍— ‍0.32， P<0.001）， respectively， that in those with a normal menopausal age. There is a dose-response relationship between menopausal time/age and the risk of NAFLD. Menopausal time is positively correlated with the association intensity of NAFLD， while menopausal age is negatively correlated with the association intensity of NAFLD. ConclusionThe longer the menopause time and the earlier the menopause age， the ligher the risk of NAFLD.

ObjectiveTo investigate the association between serum creatinine/cystatin C ratio （CCR） and nonalcoholic fatty liver disease （NAFLD） based on the NHANES database， and to evaluate the potential significance of CCR as an indicator reflecting the metabolic status of the body. MethodsBased on the data from the NHANES database in 1999‍ ‍—‍ ‍2004， a total of 4 217 participants were enrolled and divided into NAFLD group with 1 726 participants and non-NAFLD group with 2 491 participants. CCR was compared between the two groups， and the association between CCR and NAFLD was analyzed. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression model was used to investigate the association between CCR and NAFLD； CCR was divided into 4 groups based on quartiles， and odds ratio （OR） and 95% confidence interval （CI） in the regression model was calculated with the first quartile as reference. In addition， the restricted cubic spline analysis was used to investigate whether there was a non-linear relationship between CCR and NAFLD， and interaction items were introduced into the Logistic regression model to perform an interaction analysis. Subgroup analyses were performed based on the stratification of variables to investigate the difference in the association between CCR and NAFLD in different populations. ResultsThe non-NAFLD group had a significantly higher CCR than the NAFLD group （Z=-4.76，P<0.01）. The Logistic regression analysis showed that in model 1 without adjustment of variables， CCR was negatively associated with NAFLD （OR=0.993，95%CI：0.989‍ ‍—‍ ‍0.996，P<0.01）， and in model 3 with adjustment of all variables， CCR was still negatively associated with NAFLD （OR=0.986，95%CI：0.981‍ ‍—‍ ‍0.991，P<0.01）. The analysis of CCR based on quartiles showed a significant association between the increase in CCR and the reduction in the risk of NAFLD. In model 3， compared with the individuals with the lowest quartile of CCR， the individuals with the highest quartile of CCR had a significantly lower risk of NAFLD （OR=0.426，95%CI：0.316‍ ‍—‍ ‍0.574，P<0.01）. Further interaction and subgroup analyses showed that the interaction between CCR and age/sex had a statistical significance （P_interaction<0.01 and P_interaction=0.04）. The subgroup analysis based on age showed a more significant association between CCR and NAFLD in the middle-aged population （≤60 years） （OR=0.982，95%CI：0.976‍ ‍—‍ ‍0.987）， and the subgroup analysis based on sex showed a stronger association between CCR and NAFLD in women （OR=0.979，95%CI：0.972‍ ‍—‍ ‍0.986）. ConclusionThis study shows a significant negative association between CCR and NAFLD， and such association is more significant in middle-aged individuals and women.

[This corrects the article DOI: 10.1016/j.apsb.2021.07.004.].