Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Cardiac fibrosis(CF) is a cardiac pathological process characterized by excessive deposition of extracellular matrix(ECM). When the heart is damaged by adverse stimuli, cardiac fibroblasts are activated and secrete a large amount of ECM, leading to changes in cardiac fibrosis, myocardial stiffness, and cardiac function declines and accelerating the development of heart failure. There is a close relationship between heart yin deficiency and cardiac fibrosis, which have similar pathogenic mechanisms. Heart Yin deficiency, characterized by insufficient Yin fluids, causes the heart to lose its nourishing function, which acts as the initiating factor for myocardial dystrophy. The deficiency of body fluids leads to stagnation of blood flow, resulting in blood stasis and water retention. Blood stasis and water retention accumulate in the heart, which aligns with the pathological manifestation of excessive deposition of ECM, as a tangible pathogenic factor. This is an inevitable stage of the disease process. The lingering of blood stasis combined with water retention eventually leads to the generation of heat and toxins, triggering inflammatory responses similar to heat toxins, which continuously stimulate the heart and cause the ultimate outcome of CF. Considering the syndrome of heart Yin deficiency, traditional Chinese medicine capable of nourishing Yin, activating blood, and promoting urination can reduce myocardial cell apoptosis, inhibit fibroblast activation, and lower the inflammation level, showing significant advantages in combating CF.
Humans ; Fibrosis/drug therapy* ; Animals ; Yin Deficiency/metabolism* ; Myocardium/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

BACKGROUND: Medical informatics accumulated vast amounts of data for clinical diagnosis and treatment. However, limited access to follow-up data and the difficulty in integrating data across diverse platforms continue to pose significant barriers to clinical research progress. In response, our research team has embarked on the development of a specialized clinical research database for cardiology, thereby establishing a comprehensive digital platform that facilitates both clinical decision-making and research endeavors. METHODS: The database incorporated actual clinical data from patients who received treatment at the Cardiovascular Medicine Department of Chinese PLA General Hospital from 2012 to 2021. It included comprehensive data on patients' basic information, medical history, non-invasive imaging studies, laboratory test results, as well as peri-procedural information related to interventional surgeries, extracted from the Hospital Information System. Additionally, an innovative artificial intelligence (AI)-powered interactive follow-up system had been developed, ensuring that nearly all myocardial infarction patients received at least one post-discharge follow-up, thereby achieving comprehensive data management throughout the entire care continuum for high-risk patients. RESULTS: This database integrates extensive cross-sectional and longitudinal patient data, with a focus on higher-risk acute coronary syndrome patients. It achieves the integration of structured and unstructured clinical data, while innovatively incorporating AI and automatic speech recognition technologies to enhance data integration and workflow efficiency. It creates a comprehensive patient view, thereby improving diagnostic and follow-up quality, and provides high-quality data to support clinical research. Despite limitations in unstructured data standardization and biological sample integrity, the database's development is accompanied by ongoing optimization efforts. CONCLUSION The cardiovascular specialty clinical database is a comprehensive digital archive integrating clinical treatment and research, which facilitates the digital and intelligent transformation of clinical diagnosis and treatment processes. It supports clinical decision-making and offers data support and potential research directions for the specialized management of cardiovascular diseases.

Objective:To explore the mechanism of Danxing Zhishuang Prescription in the treatment of Parkinson's disease (PD) by combining network pharmacology with animal models.Methods:TCMSP, BATMAN database, Genecards, and OMIM databases were retrieved to obtain the active components and action targets of Danxing Zhishuang Prescription. Venny 2.1.0 was used to intersect drug targets and PD related genes, and a protein interaction network of the intersection targets was constructed using the STRING 12.0 platform. Topology analysis was performed using Cytoscape 3.10.0 software to identify the key targets of Danxing Zhishuang Prescription on PD; GO functional and KEGG pathway enrichment analysis was performed on key targets using the WeChat platform, and molecular docking was validated through AutoDockTools 1.5.7. Using a random number table method, mice were divided into a blank control group, a model group, and a Danxing Zhishuang Prescription group, with 20 mice in each group; except for the blank group, all other groups of mice were orally administered fisetin to prepare PD models; Danxing Zhishuang Prescription group was orally administered with concentrated Danxing Zhishuang Prescription at a dosage of 10.5 g/kg, while the blank group and model group were orally administered with 0.2 ml of physiological saline for 21 days; Western blot was used to detect the expressions of Akt1, Bcl-2, Bax, and α-Syn proteins.Results:359 intersection targets, 69 core targets, and 185 active components were obtained the treatment of PD with Danxing Zhishuang Prescription. The main active components included quercetin, kaempferol, phenylalanine, etc., and the key targets were AKT1, TP53, TNF, ESR1, etc. KEGG analysis revealed several key signaling pathways, such as AGE-RAGE, PI3K-Akt, fluid shear stress and atherosclerosis signaling pathways. The validation experiment results showed that compared with the model group, the expression of Bcl-2 protein was up-regulated ( P<0.01), and the expressions of Bax, Akt1, and α-Syn proteins were down-regulated in the Danxing Zhishuang Prescription group ( P<0.01). Conclusions:Danxing Zhishuang Prescription has the advantages of multi target and multi pathway treatment for PD. Its mechanism may be related to down-regulating the expressions of Bax, Akt1, and α-Syn proteins, improving brain blood supply, regulating neurotransmitter balance, inhibiting oxidative stress response, and promoting nerve regeneration.

Gastric polyps, as a common digestive system disease, have shown an increasing detection rate and are regarded as one of the precancerous states of gastric cancer. In TCM, gastric polyps can be classified as diseases such as "stomachache" and "fullness and distension in the stomach". TCM holds that the disease is often related to the accumulation of pathogenic factors such as phlegm and blood stasis in the body to form "kenang", which has the characteristics of insidiousness, stubbornness, and recurrence. Deficiency of healthy qi and disorder of qi movement can lead to the adhesion of phlegm and blood stasis, which highly aligns with the etiology and pathogenesis of gastric polyps. The treatment principles are promoting blood circulation to remove blood stasis, regulating qi movement, and strengthening the body resistance to consolidate the essence. Understanding the etiology, pathogenesis, and treatment principles of gastric polyps from the theory of "kenang" has important guiding significance for clinical diagnosis and treatment, providing new ideas and methods for the treatment of gastric polyps.

OBJECTIVES: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats. CONCLUSIONS Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.
Animals ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Rats ; MAP Kinase Kinase Kinases/metabolism* ; Signal Transduction/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; NF-kappa B/metabolism* ; Isoflavones/therapeutic use* ; Male ; Arthritis, Experimental/drug therapy* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/metabolism*

Objective:To study the effect of angiopoietin-1(Ang-1)and tyrosine kinase receptor 2(Tie2)inhibitor on glucose transportation in the human umbilical vein endothelial cells(HUVECs)cultured under high glucose conditions,and to clarify its mechanism.Methods:The HUVECs were cultured in high glucose(30 mmol·L?1)in vitro and treated with 0,200,500,1 000,and 2 000 μg·L?1 Ang-1 and 0,2 500,5 000,and 7 500 nmol·L?1 Tie2 inhibitor;cell counting kit-8(CCK-8)method was used to detect the cell activity to screen the optimal concentrations of Ang-1 and Tie2 inhibitor.Glucose kit was used to detect the glucose level in the supernatant of the HUVECs after Ang-1 intervention.The HUVECs were randomly divided into blank control group(NG group),high glucose group(HG group),HG+Tie2 inhibitor group(HG+In-Tie2 group),HG+Ang-1 group,HG+Ang-1+Tie2 inhibitor group(HG+Ang-1+In-Tie2 group),and HG+Ang-1+phosphatidylinositol 3-kinase(PI3K)inhibitor group(HG+Ang-1+LY294002 group).5-Ethynyl-2'-deoxyuridine(EdU)method was used to detect the proliferation activities of the cells in various groups;YO-PRO-1/PI method was used to detect the apoptotic rates of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Ang-1 mRNA and Tie2 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Tie2,glucose transporter 1(GLUT1),and glucose transporter 4(GLUT4)proteins and the ratios of phosphorylated PI3K(p-PI3K)/PI3K and phosphorylated protein kinase B(p-AKT)/AKT in the cells in various groups.Results:The CCK-8 assay results showed that compared with 0 μg·L?1 Ang-1 group,the activity of the HUVECs was significantly increased after treated with 200 μg·L?1 Ang-1 for 48 h(P<0.01);compared with 0 nmol·L?1 Tie2 inhibitor group,the activity of the HUVECs was significantly decreased after treated with 2 500、5 000 and 7 500 nmol·L?1 Tie2 inhibitor(P<0.01);the optimal concentrations of Ang-1 and Tie2 inhibitor were 200 μg·L?1 and 2 500 nmol·L?1,respectively.Compared with NG group,the glucose level in the supernatant of the HUVECs in HG group was significantly increased(P<0.01);compared with HG group,the glucose level in the supernatant of the HUVECs in Ang-1 group was significantly decreased(P<0.01).The EdU assay results showed that compared with NG group,the proliferation activity of the HUVECs in HG group was significantly decreased(P<0.01);compared with HG group,the proliferation activity of the HUVECs in HG+In-Tie2 group was significantly decreased(P<0.01),and the proliferation activity of the HUVECs in HG+Ang-1 group was significantly increased(P<0.01);compared with HG+Ang-1 group,the proliferation activities of the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).The YO-PRO-1/PI assay results showed that compared with NG group,the apoptotic rate of the HUVECs in HG group was significantly increased(P<0.01);compared with HG group,the apoptotic rate of the HUVECs in HG+In-Tie2 group was significantly increased(P<0.01),and the apoptotic rate of the HUVECs in HG+Ang-1 group was significantly decreased(P<0.01);compared with HG+Ang-1 group,the apoptotic rates of the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly increased(P<0.01).The RT-qPCR results showed that compared with NG group,the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG group and HG+In-Tie2 group were significantly decreased(P<0.01);compared with HG group,the expression levels of Ang-1 mRNA and Tie2 mRNA in HG+In-Tie2 group were significantly decreased(P<0.01),and the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG+Ang-1 group were significantly increased(P<0.05);compared with HG+Ang-1 group,the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.05 or P<0.01).The Western blotting results showed that compared with NG group,the expression level of Tie2 protein in the HUVECs in HG group was significantly decreased(P<0.01),and the expression levels of GLUT1 and GLUT4 proteins were significantly increased(P<0.01);compared with HG group,the expression levels of Tie2,GLUT1,and GLUT4 proteins in the HUVECs in HG+In-Tie2 group were significantly decreased(P<0.01),the expression level of Tie2 protein in the HUVECs in HG+Ang-1 group was significantly increased(P<0.01),and the expression levels of GLUT1 and GLUT4 proteins were significantly decreased(P<0.01);compared with HG+Ang-1 group,the expression levels of Tie2,GLUT1,and GLUT4 proteins in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).Compared with NG group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG group were significantly increased(P<0.01);compared with HG group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+In-Tie2 group were significantly decreased(P<0.01),and the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+Ang-1 group were significantly decreased(P<0.01);compared with HG+Ang-1 group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).Conclusion:Ang-1 down-regulates the expressions of GLUT1 and GLUT4 in the HUVECs cultured under high glucose conditions;the binding of Ang-1 to Tie2 may down-regulate GLUT1 and GLUT4 via the PI3K/AKT signaling pathway to participate in the glucose transportation in the HUVECs cultured under high glucose conditions.

Objective To investigate the prevalence of scoliosis and congenital heart disease(CHD)and their correlation among children and adolescents of Drung nationality in Yunnan Province.Methods A cross-sectional survey was conducted in November 2022 among all Drung school-aged children and adolescents aged 5-18 years in Gongshan Drung and Nu Autonomous County,Yunnan Province.Visual inspection,Adams for-ward flexion test,and trunk rotation angle(ATR)measurement were comprehensively used for school prelim-inary screening of scoliosis.Individuals who tested positive in the school preliminary screening underwent fur-ther X-ray examination for auxiliary diagnosis.Cardiac auscultation and echocardiography were used for school preliminary screening of CHD.The personal information of the screening subjects,the screening results,etc.were recorded.The prevalence of scoliosis and CHD among children and adolescents of the Drung nationality and the relationship between the two diseases were statistically analyzed,and the positive predictive value of school-based scoliosis screening and its influencing factors were also analyzed.Results A total of 1 036 chil-dren and adolescents of Drung nationality were enrolled,with a mean age of(10.72±3.75)years,icluding 542 males and 494 females.A total of 45 subjects tested positive for scoliosis in the school preliminary screening,with a preliminary positive rate of 4.34%.A total of 22 cases were finally diagnosed with scoliosis,with a prevalence rate of 2.12%.Among them,21 cases were idiopathic scoliosis(accounting for 95.45%),and 1 case was congenital scoliosis(accounting for 4.55%).The prevalence rate was higher in females(2.83%)than that in males(1.48%),higher in the 10 to 18-year-old group(2.30%)than that in the 5 to<10-year-old group(1.87%),and higher in the secondary school group(2.78%)than that in the primary school group(1.78%),hut there were no statistically significant differences(P>0.05).Most idiopathic scoliosis cases were mild(Cobb angle 10° to<20°,90.48%)and classified as Lenke type Ⅴ(57.14%).Two cases of CHD were confirmed,both of which were atrial septal defects,with a prevalence rate of 0.19%.The co-occurrence rate of idiopathic scoliosis and CHD was 4.76%(1/21).The positive predictive value of school-based scoliosis pre-liminary screening was only 48.89%.When the BMI was<18.5 kg/m2,the positive predictive value was sig-nificantly higher than that for BMI≥18.5 kg/m2(P<0.05).Conclusion The prevalence rate of scoliosis a-mong adolescents of the Drung ethnic group in Yunnan Province is 2.12%,predominantly idiopathic scoliosis,with Lenke type V being the most common classification.The prevalence rate of congenital heart disease is 0.19%.BMI is a significant influencing factor for the positive predictive value of school-based scoliosis prelimi-nary screening.