Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

BACKGROUND:Bone defects can directly affect the success rate and long-term stability of dental implants.Studies have shown that salidroside has the ability to promote the proliferation and differentiation of osteoblasts,but less is reported on its pathways related to osteogenic differentiation. OBJECTIVE:To investigate the effects of salidroside on the proliferation and differentiation of MC3T3-E1 cells and the expression of related genes and proteins through in vitro cell experiments. METHODS:Cell counting kit-8 test and alkaline phosphatase test were used to determine the optimal concentration of salidroside(0.5,1,5,10,and 50 μmol/L)in promoting the proliferation and differentiation of MC3T3-E1 cells.There were four groups in the experiment:control group,salidroside group,salidroside+LY294002 group,and LY294002 group,which were cultured with osteogenic induction solution,osteogenic induction solution containing 10 μmol/L salidroside,osteogenic induction solution containing 10 μmol/L salidroside+10 μmol/L LY294002,and osteogenic induction solution containing 10 μmol/L LY294002,respectively.The effects of salidroside and LY294002,an inhibitor of the PI3K/Akt signaling pathway,on the expressions of genes and proteins related to osteogenesis were observed. RESULTS AND CONCLUSION:Cell counting kit-8 assay and alkaline phosphatase assay showed that salidroside promoted the proliferation of MC3T3-E1 cells most significantly at 10 μmol/L.Compared with the control group,salidroside could promote mineralization,promote cell adhesion,reduce cell death,increase mRNA expression of Runx-2,osteocalcin and osteopontin(P<0.01),and increase protein expression of Runx-2 and p-Akt(P<0.01).However,the addition of LY294002 reversed the above results.These findings indicate that salidroside can promote the mineralization of MC3T3-E1 cells and the expression of osteogenesis-related genes and proteins,which may be related to the activation of PI3K/Akt signaling pathway.

Jansen-de Vries syndrome, also known as intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, is a rare autosomal dominant disorder characterized by multisystem involvement. This article reports the case of a young child who presented with global developmental delay, gastrointestinal dysfunction, intellectual disability, and short stature. Distinct facial features included a broad forehead, low nasal bridge, thin upper lip, and widely spaced and misaligned teeth. Additional phenotypic findings involved small hands and feet, as well as digital anomalies. Through whole-exome sequencing (WES) and copy number variation (CNV) analysis, a pathogenic variant was identified in the PPM1D gene: c.1281G > A (p.Trp427Ter). This report also reviews the current literature on the clinical characteristics, diagnostic approaches, and therapeutic advances related to this condition, aiming to provide valuable insights for its clinical diagnosis and management.

ObjectiveTo perform a multi-source data fusion analysis of the clinical literature on traditional Chinese medicine （TCM） treatment of gout， explore the front hotspots in this field， and mine the clinical consensus and medication patterns in the TCM treatment of gout with the syndrome of dampness-heat accumulation， thus providing reference for the standardized treatment of this disease. MethodsCNKI， Wanfang， and VIP were searched for the relevant literature. COOC14.9/VOSviewer was used to perform multi-source data fusion analysis of clinical literature on the TCM treatment of gout and construct a visual knowledge map for exploring the research hotspots and frontiers of the TCM treatment of gout. The Traditional Chinese Medicine Inheritance Support System （V3.0） was used to establish the database of TCM treatment of gout with the syndrome of dampness-heat accumulation and explore the medication pattern and prescription characteristics. ResultsThe number of published clinical articles on the TCM treatment of gout has remained high. The research hotspots included comparative studies on the etiology and pathogenesis of gout， identification and typing， prescription composition， and clinical efficacy. A large amount of data has been accumulated in the medicine use experience and the summarization of therapeutic effects. The medication patterns in the TCM treatment of gout with the syndrome of dampness-heat accumulation were mined from the articles that were published during 2019-2023. It was revealed that clinically used drugs can be categorized into 9 groups according to their efficacy. Among them， the drugs with the effects of promoting urination and draining dampness were the richest and had the highest frequency. Meanwhile， the drugs with the effects of resolving dampness and expelling wind-dampness were also commonly used in clinical practice. The combined use of drugs with effects of eliminating dampness， resolving dampness， and expelling dampness plays a key role in the treatment of gout with the syndrome of dampness-heat accumulation. Secondly， heat-clearing drugs are also commonly used， with the types and frequency close to those of urination-promoting and dampness-draining drugs. In addition， drugs with the effects of activating blood and eliminating stasis are commonly prescribed. The prescriptions modified from Simiaowan were commonly used， and the most commonly used drug was Coicis Semen. The analysis of drug combination applications and core drug combinations showed that the core drugs used in the treatment of gout with the syndrome of dampness-heat accumulation were Coicis Semen， Phellodendri Chinensis Cortex， Atractylodis Rhizoma， Achyranthis Bidentatae Radix， Smilacis Glabrae Rhizoma， Dioscoreae Hypoglaucae Rhizoma， Alismatis Rhizoma， and Clematidis Radix et Rhizoma， which were closely related. Coicis Semen was an assistant and guide drug in Simiaowan， while it was the most commonly used in the treatment of gout with the syndrome of dampness-heat accumulation. ConclusionsClinical studies on the TCM treatment of gout are in-depth and diverse， and the core medicinal combination was essentially modified Simiaowan. Coicis Semen， with the highest frequency， has a special efficacy in the treatment of gout with the syndrome of dampness-heat accumulation and is worthy of further in-depth study.

Objective:To discuss the role of angiopoietin-like protein 6(ANGPTL6)in liver fibrosis,and to analyze the improving effect of engineered exosome(Exo)-delivered ANGPTL6 mRNA on liver fibrosis.Methods:A total of 12 C57BL/6 mice were randomly divided into olive oil group(OIL group)(intraperitoneally injected with olive oil)and carbon tetrachloride(CCl4)group(intraperitoneally injected with a mixture of olive oil and CCl?),with 6 mice in each group;another 12 C57BL/6 mice were randomly divided into control group(fed a with methionine-choline sufficient diet)and methionine-choline deficient(MCD)group(fed a with MCD diet),and two kinds of mouse liver fibrosis models were established.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the ANGPTL6 mRNA and protein expression levels in liver tissue of the mice in various groups.A total of 30 mice were randomly divided into olive oil+phosphate buffered saline(PBS)group(OIL+PBS group)(intraperitoneally injected with olive oil twice a week for 8 weeks,then injected with PBS buffer by tail vein twice a week for 6 weeks),CCl4+Exo-green fluorescent protein(GFP)mRNA group(established liver fibrosis model by intraperitoneal injection of CCl4 mixture and were injected by tail vein with engineered Exo loaded with GFP mRNA for 6 weeks),and CCl?+Exo-ANGPTL6 mRNA group(established liver fibrosis model by intraperitoneal injection of CCl4 mixture and were injected by tail vein with engineered Exo loaded with ANGPTL6 mRNA for 6 weeks),with 10 mice in each group.The mice in CCl4+Exo-GFP mRNA group and CCl4+Exo-ANGPTL6 mRNA group were injected with engineered Exo twice a week,20 μg per mouse each time(volume 100 μL).ELISA method was used to detect the serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities in the mice in various groups;Masson staining and Sirius red staining were used to observe the collagen deposition in liver tissue of the mice in various groups;immunohistochemistry method was used to detect the α-smooth muscle actin(α-SMA)expression levels in liver tissue of the mice in various groups;RT-qPCR method was used to detect the expression levels of α-SMA,collagen type Ⅰ alpha 1 chain(Col1a1),transforming growth factor β1(TGF-β1),and tissue inhibitor of metalloproteinase 1(TIMP-1)mRNA in liver tissue of the mice in various groups.Results:The bioinformatics analysis results showed that ANGPTL6 expression was significantly down-regulated in activated hepatic stellate cell(aHSC).The ultrasound examination results showed that the liver surface of the mice in OIL group was fine and smooth;compared with OIL group,the liver section of the mice in CCl? group was rough and uneven.The RT-qPCR and Western blotting results showed that compared with OIL group,the ANGPTL6 mRNA and protein expression levels in liver tissue of the mice in CCl? group were significantly decreased(P<0.05).The engineered Exo extracted from the supernatant of HEK293T cells had intact structure and could be largely enriched in the fibrotic liver after tail vein injection,with GFP protein being largely expressed in the liver.The ELISA assay results showed that compared with OIL+PBS group,the ALT and AST activities in CCl4+Exo-GFP mRNA group were significantly increased(P<0.05);compared with CCl4+Exo-ANGPTL6 mRNA group,the serum ALT and AST activities in CCl4+Exo-GFP mRNA group were significantly decreased(P<0.05).The Masson staining and Sirius red staining results showed that compared with OIL+PBS group,the collagen deposition in liver tissue of the mice in CCl?+Exo-GFP mRNA group was significantly increased,and the relative collagen area was increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the collagen deposition in tissue liver of the mice in CCl?+Exo-ANGPTL6 mRNA group was significantly decreased,and the relative collagen area was decreased(P<0.05).The immunohistochemistry results showed that compared with OIL+PBS group,the α-SMA protein expression level in liver tissue of the mice in CCl?+Exo-GFP mRNA group was significantly increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the α-SMA protein expression level in liver tissue of the mice in CCl?+Exo-ANGPTL6 mRNA group was significantly decreased(P<0.05).The RT-qPCR results showed that compared with OIL+PBS group,the expression levels of Col1a1,α-SMA,TGF-β1,and TIMP-1 mRNA in liver tissue of the mice in CCl?+Exo-GFP mRNA group were significantly increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the expression levels of Col1a1,α-SMA,TGF-β1,and TIMP-1 mRNA in liver tissue of the mice in CCl?+Exo-ANGPTL6 mRNA group were significantly decreased(P<0.05).Conclusion:Engineered Exo-delivered ANGPTL6 mRNA injected via the tail vein in the mice is mainly enriched in the liver,and engineered Exo delivery of ANGPTL6 mRNA has an improving effect on liver fibrosis in the mice.

Objective To investigate the potential mechanism by which dihydromyricetin(DHM)ameliorates diabetic nephropathy(DN),and to screen and validate its possible key molecular targets.Methods A DN model was established using db/db mice,and 100 mg/(kg·d)DHM was administered via gavage 5 d per week for totally 10 weeks.Renal morphological changes were observed after staining to evaluate the effects of DHM.GSE161885 and GSE270526 datasets were obtained from the Gene Expression Omnibus(GEO)database and analyzed in combination with the GeneCards database to screen for DN-related differentially expressed genes(DEGs).Protein-protein interaction(PPI)network and molecular docking were employed to predict potential DHM targets.Western blotting and immunofluorescence staining were performed to detect the effects of DHM on pyroptosis-related pathways in the renal tissues of db/db mice and in high glucose(HG)-induced human renal tubular epithelial cells(HK-2).The specific NLR family pyrin domain containing protein 3(NLRP3)inhibitor MCC950 was also used to validate the predicted mechanism.Results In vivo experiments showed that DHM significantly ameliorated renal pathological damage in db/db mice,alleviated glomerular hypertrophy and mesangial expansion,and markedly reduced Paller scores(P<0.001).Immunofluorescence staining revealed significantly weakened fluorescence signals for α-smooth muscle actin(α-SMA),fibronectin,and collagen Ⅰ in renal tissues.Western blot results showed that the expression levels of collagen Ⅰ,collagen Ⅲ,α-SMA,and transforming growth factor beta 1(TGF-β1)were significantly decreased(P<0.05).A total of 16 DN-related DEGs were identified.Enrichment analysis revealed that these genes were primarily enriched in pathways such as viral protein interactions,cytokine-cytokine receptor interaction,and the AGE-RAGE signaling pathway in diabetic complications,and were primarily involved in gene functions such as the positive regulation of lymphocyte-mediated immunity,positive regulation of adaptive immune response,and chemokine activity.Molecular docking confirmed NLRP3 as a potential target of DHM.In vivo validation showed that DHM significantly down-regulated gasdermin-D(GSDMD)fluorescence signals and inhibited the expression of pyroptosis-related proteins including NLRP3,Caspase 1,Cleaved-Caspase 1,interleukin 18(IL-18),and GSDMD(P<0.05).In vitro studies further confirmed that both DHM and the specific NLRP3 inhibitor MCC950 alleviate high glucose-induced fibrosis and pyroptosis in HIC-2 cells.Conclusion DHM can ameliorate the progression of DN,and its mechanism is related to inhibiting NLRP3 inflammasome-mediated pyroptosis,thereby alleviating renal inflammation and fibrosis.

Rodent models play a crucial role in research on human periodontal diseases,providing key evidence for investigation into the pathological mechanisms of periodontal bone defects.Relevant research in the field involves gene expression,inflammatory regulation mechanisms,host-microbial interactions,as well as disease resolution and healing processes.Research methodology in the field falls under 2 categories-periodontal inflammation models and surgical defect models.The former simulates periodontal defects by inducing periodontal diseases,while the latter constructs clinically simulated periodontal defects through surgical removal of periodontal tissue.However,the currently available animal models of periodontitis face challenges in simultaneously capturing the disease complexity,tracking dynamic repair processes,and meeting translational needs.Herein,we reviewed and summarized the methods and characteristics of periodontal disease modeling in recent years.We proposed the establishment of a multimodal assessment framework integrating technologies such as spatial transcriptomics,single-cell sequencing,and in vivo fluorescence imaging,which may serve as a critical pathway for overcoming existing research challenges.

Objective To explore the research hotspots and development trends of microbiota-gut-brain axis(MGBA)related literature both domestically and internationally.Methods Relevant MGBA literature from 2000 to 2023 was retrieved from the Web of Science Core Collection,and bib-liometric and visualization analyses were conducted using CiteSpace 6.3.R1 software.Results A total of 857 MGBA-related articles were analyzed.China and the United States are representative countries in this field,with CRYAN J F and University College Cork being the most influential author and the most productive institution,respectively.In recent years,high-frequency research had fo-cused on neurodegenerative diseases,intra-and extra-axis interactions with the body,and interventions involving short-chain fatty acids(SCFAs),tryptophan metabolism and serotonin.Conclusion The research in MGBA continues to be hotspot,and the research focus gradually transit from the verifica-tion of the relationship with diseases to the intra-axis interaction mechanism.The research hotspot of nervous system related diseases has been enduring in this field,and the therapeutic measures targeting the metabolites of intestinal flora and metabolomics are expected to become the future research trend in this field.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.