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.

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.

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 observe the clinical efficacy and safety of Dizhuo Huayu prescription combined with catgut embedding therapy in patients with nonalcoholic steatohepatitis （NASH） and dyslipidemia and explore the effect of the combined therapy on inflammatory cytokines interleukin （IL）-18 and IL-1β. MethodsA total of 82 patients with NASH and dyslipidemia from the Gastroenterology Department of the First Affiliated Hospital of Henan University of Chinese Medicine were randomly divided into a control group and a treatment group， with 41 patients in each group. The control group received Polyene Polyenylphosphatidylcholine Capsules， while the treatment group received Dizhuo Huayu prescription granules combined with catgut embedding. The treatment duration was 24 weeks for both groups. At weeks 0， 12， and 24， the traditional Chinese medicine （TCM） syndrome score， body mass index （BMI）， liver fat content assessed by Fibroscan （CAP value）， the level of alanine transaminase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transferase （GGT）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acid （FFA）， and the expression of inflammatory cytokines IL-18 and IL-1β in serum were observed. Adverse reactions in both groups were recorded. ResultsA comparison of the comprehensive therapeutic effects between the two groups after 24 weeks of treatment revealed that the total effective rate was 62.16% （23/37） in the control group and 85.71% （30/35） in the treatment group， with a statistically significant difference （χ² = 5.14， P<0.05）. At weeks 12 and 24 after treatment， the TCM syndrome score， BMI， CAP value， TC， TG， LDL-C， and FFA were all significantly lower in both groups compared to pre-treatment levels， while the HDL-C level significantly increased （P<0.05）. The effect was better at week 24 （P<0.05） than at week 12 （P<0.05）， and the treatment group showed better outcomes than the control group at weeks 12 and 24 after treatment （P<0.05）. After 24 weeks of treatment， both groups exhibited significant reductions in IL-18 and IL-1β levels （P<0.05）. The treatment group demonstrated superior efficacy compared to the control group after treatment （P<0.05）. Both groups experienced decreases in ALT， AST， and GGT levels after treatment （P<0.05）. However， there were no statistically significant differences between the 12-week and 24-week post-treatment values within each group， nor were there significant differences between the two groups. No significant adverse reactions were observed in both groups. ConclusionThe Dizhuo Huayu prescription combined with catgut embedding therapy is safe and effective in treating patients with NASH and dyslipidemia， exhibiting hepatoprotective， anti-inflammatory， lipid-regulating， and weight-reducing effects.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*