ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis （UC） mice based on adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS Male BALB/c mice were randomly divided into control group， model group， inhibitor group （AMPK inhibitor Compound C 20 mg/kg）， paeoniflorin low-， medium- and high-dose groups （paeoniflorin 12.5， 25， 50 mg/kg）， high- dose of paeoniflorin+inhibitor group （paeoniflorin 50 mg/kg+Compound C 20 mg/kg）， with 8 mice in each group. Except for the control group， mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently， mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally， once a day， for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration， colon length， malondialdehyde （MDA） content， and activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in colon tissues were measured； histopathological morphology of colon tissues， tight junctions between intestinal epithelial cells， and histopathological scoring were all observed and evaluated； the mRNA expressions of AMPK and Nrf2， as well as the protein expressions of heme oxygenase-1（HO-1）， occludin and claudin-1， were all determined in colon tissue. RESULTS Compared with model group， paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue， as well as improved tight junction damage between intestinal epithelial cells. Additionally， significant increases or upregulations were observed in body weight， colon length， activities of SOD and GSH-Px， phosphorylation level of AMPK， and protein expression of Nrf2， HO-1， occludin， claudin-1， and mRNA expressions of AMPK and Nrf2； concurrently， MDA content and histopathological scores were significantly reduced （P＜ 0.05 or P＜0.01）. In contrast， the inhibitor group showed comparable （P＞0.05） or worse （P＜0.05 or P＜0.01） indicators compared to the model group. Conversely， the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin （P＜0.01）. CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice， improve tight junctions between epithelial cells， upregulate the expression of related proteins， and promote the expression and secretion of antioxidant-promoting molecules， thereby ameliorating UC； its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.

Triggering receptor expressed on myeloid cells 2 （TREM2） is expressed in resident non-parenchymal cells （NPCs） and is involved in various pathological processes including liver inflammation and immunoregulation. In recent years， TREM2 has attracted attention in the field of acute and chronic liver diseases， and more and more studies have shown that TREM2 is a potential target for the treatment of acute and chronic liver diseases； however， there is a lack of systematic summary for the mechanism of action of TREM2 in acute and chronic liver diseases. Therefore， this article reviews the latest research advances in the regulatory role of TREM2 in acute and chronic liver diseases， in order to provide new ideas for the clinical prevention and treatment of acute and chronic liver diseases.

BACKGROUND:Chronic myofascial trigger points can identify differential metabolite changes through non targeted metabolomics techniques,helping to understand and further explore the pathophysiological processes and pathogenesis of chronic myofascial trigger points from the perspective of endogenous small molecule metabolites. OBJECTIVE:To investigate potential biomarkers and related metabolic pathways based on urine metabolomics in the rat model of chronic myofascial trigger points. METHODS:Sixteen Sprague-Dawley rats were randomly divided into a model group and a normal group.The model group was used to establish a chronic myofascial trigger point animal model by combining blunt hitting with centrifugal exercise(treadmill slope:-16°,running speed:16 m/min,training time:90 minutes each),once a week for 8 continuous weeks,with 4 weeks off.After 12 weeks of modeling,the metabolic cage method was used to collect urine from rats at 24 hours after modeling.Liquid chromatography-mass spectrometry non-targeted metabolomics technology was used to detect metabolic profiles in the urine samples,screen common differential metabolites,and conduct bioinformatics analysis. RESULTS AND CONCLUSION:Compared with the normal group,there were 32 differential metabolic markers in the model group,of which 21 were upregulated and 11 were downregulated.A total of 14 differential metabolites were identified as potential biomarkers based on the value of variable important in projection greater than 3.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes indicated that the formation of chronic myofascial trigger points is closely related to metabolic pathways such as primary bile acid biosynthesis and arachidonic acid metabolism.

Objective: To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases. Methods: This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same. Results: ①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05). Conclusion Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.

ObjectiveBased on a new method for animal model evaluation， this study aims to analyze the characteristics of diseases and syndromes of existing animal models of attention deficit hyperactivity disorder （ADHD） from both traditional Chinese medicine （TCM） and western medical perspectives and propose suggestions for improvement. MethodsA systematic search of the China National Knowledge Infrastructure （CNKI） and PubMed was conducted for literature on ADHD animal models. According to TCM and western medical diagnostic criteria， core and accompanying symptoms of the models were assigned with scores to comprehensively evaluate the clinical consistency. ResultsThe selection of experimental animals for ADHD models primarily involved rodents， with modeling methods including genetic， chemical induction， and environmental induction. The average consistency of clinical diseases and syndromes with TCM and western medicine was 45.19% and 49.42%， respectively. The spontaneously hypertensive （SHR） rats and nicotine/smoking models had the highest consistency with TCM， while the social isolation models had the highest consistency with western medicine. Most models were guided by western medicine theories， which can meet the surface validity and structural validity requirements of western medicine but lacked precise differentiation of TCM syndromes. ConclusionExisting ADHD animal models primarily focus on a single genotype or environmental factor， lacking comprehensive consideration of multigenic interactions and environmental factors. Moreover， the selection of model evaluation indicators is relatively singular， primarily focusing on "disease" indicators， while TCM "syndrome" indicators have not been fully considered. It is recommended to introduce a "formula-to-syndrome" approach in the preparation of TCM models for ADHD and establish and improve an evaluation system of animal models combining diseases and syndromes， so as to provide a solid foundation for future experimental research.

ObjectiveBased on a new method for animal model evaluation， this study aims to analyze the characteristics of diseases and syndromes of existing animal models of attention deficit hyperactivity disorder （ADHD） from both traditional Chinese medicine （TCM） and western medical perspectives and propose suggestions for improvement. MethodsA systematic search of the China National Knowledge Infrastructure （CNKI） and PubMed was conducted for literature on ADHD animal models. According to TCM and western medical diagnostic criteria， core and accompanying symptoms of the models were assigned with scores to comprehensively evaluate the clinical consistency. ResultsThe selection of experimental animals for ADHD models primarily involved rodents， with modeling methods including genetic， chemical induction， and environmental induction. The average consistency of clinical diseases and syndromes with TCM and western medicine was 45.19% and 49.42%， respectively. The spontaneously hypertensive （SHR） rats and nicotine/smoking models had the highest consistency with TCM， while the social isolation models had the highest consistency with western medicine. Most models were guided by western medicine theories， which can meet the surface validity and structural validity requirements of western medicine but lacked precise differentiation of TCM syndromes. ConclusionExisting ADHD animal models primarily focus on a single genotype or environmental factor， lacking comprehensive consideration of multigenic interactions and environmental factors. Moreover， the selection of model evaluation indicators is relatively singular， primarily focusing on "disease" indicators， while TCM "syndrome" indicators have not been fully considered. It is recommended to introduce a "formula-to-syndrome" approach in the preparation of TCM models for ADHD and establish and improve an evaluation system of animal models combining diseases and syndromes， so as to provide a solid foundation for future experimental research.