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.

The theory of constitution in traditional Chinese medicine （TCM） has emerged as a new discipline in recent years. Constitution plays a vital role in the onset，progression，transformation，and prognosis of diseases. At present，some clinical scholars have adopted a novel diagnostic and treatment model of "constitution differentiation-disease identification-syndrome differentiation"，in which constitution is regarded as a core element throughout the diagnostic and therapeutic process. Constitution is closely associated with etiology，onset，pathogenesis，syndrome differentiation，and treatment. Against this background，the construction of animal models based on constitution holds far-reaching significance for advancing clinical research. This paper focuses on the construction and evaluation of rodent models with Qi-deficiency constitution，aiming to explore how to further induce Qi-deficiency syndromes and related disease states on the basis of Qi-deficiency constitution models，thereby developing an integrated animal model that embodies the trinity of "constitution-disease-syndrome". The establishment of this model not only provides a solid experimental foundation for the development of new therapies and drugs in TCM targeting specific constitutions，diseases，and syndromes，but also greatly promotes the modernization and scientific advancement of TCM theory. By comprehensively applying multidisciplinary technologies and methods，the study evaluates the model's validity，reliability，and practicality，with the aim of opening new avenues for future research in TCM and promoting the development of the field.

The theory of constitution in traditional Chinese medicine （TCM） has emerged as a new discipline in recent years. Constitution plays a vital role in the onset，progression，transformation，and prognosis of diseases. At present，some clinical scholars have adopted a novel diagnostic and treatment model of "constitution differentiation-disease identification-syndrome differentiation"，in which constitution is regarded as a core element throughout the diagnostic and therapeutic process. Constitution is closely associated with etiology，onset，pathogenesis，syndrome differentiation，and treatment. Against this background，the construction of animal models based on constitution holds far-reaching significance for advancing clinical research. This paper focuses on the construction and evaluation of rodent models with Qi-deficiency constitution，aiming to explore how to further induce Qi-deficiency syndromes and related disease states on the basis of Qi-deficiency constitution models，thereby developing an integrated animal model that embodies the trinity of "constitution-disease-syndrome". The establishment of this model not only provides a solid experimental foundation for the development of new therapies and drugs in TCM targeting specific constitutions，diseases，and syndromes，but also greatly promotes the modernization and scientific advancement of TCM theory. By comprehensively applying multidisciplinary technologies and methods，the study evaluates the model's validity，reliability，and practicality，with the aim of opening new avenues for future research in TCM and promoting the development of the field.

Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

Objective: To identify biomolecular markers closely related to the occurrence of kidney renal clear cell carcinoma (KIRC) and verify their expression levels in clinical samples. Methods: Stage Ⅰ KIRC mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA).Principal component analysis (PCA) was used for dimensionality reduction to screen differentially expressed genes (DEGs)，which then underwent GO and KEGG analyses.Weighted gene co-expression network analysis (WGCNA) was used to screen genes significantly related to KIRC，and a protein-protein interaction (PPI) network was constructed to screen hub genes.The diagnostic value of hub genes was evaluated with receiver operating characteristic (ROC) curve，and their prognostic value was analyzed using survival curve plots.The correlation between the mRNA expressions of hub genes and the pathological stages of KIRC was analyzed.Clinical samples of 20 patients with stage Ⅰ KIRC treated in our hospital were included，and the expressions of the hub genes in cancerous and adjacent tissues were detected with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR)，Western blotting，and enzyme-linked immunosorbent assay (ELISA). Results: A total of 8223 DEGs were screened out，including 4092 up-regulated ones and 4131 down-regulated ones.GO analysis showed that DEGs were related to bioadhesion，plasma membrane composition，and transporter activity.KEGG analysis showed that DEGs were related to pathways such as cell adhesion molecules，cytokine-cytokine receptor interactions，and interactions between viral proteins and cytokines and cytokine receptors.WGCNA analysis obtained 171 genes that were significantly related to stage Ⅰ KIRC.The hub gene，lymphocyte cytosolic protein 2 (LCP2)，screened out by the PPI network，was significantly related to stage Ⅰ KIRC.The area under the ROC curve was 0.96.The expression level was negatively correlated with the overall survival rate of patients.The expression of LCP2 was related to the stage and lymph node metastasis.Clinical verification showed that the mRNA and protein relative expressions of LCP2 in KIRC tissues were significantly higher than those in adjacent tissues (P<0.000 1). Conclusion: LCP2 is significantly up-regulated in stage Ⅰ KIRC tissues and can be used as a potential biomarker for the early diagnosis and treatment of KIRC.

Asthma, a chronic inflammatory airway disease with a high global prevalence, has a complex pathogenesis, in which airway remodeling plays a key role in the chronicity of the disease. Airway remodeling involves a series of pathophysiological changes, including airway epithelial damage, proliferation of mucous glands and goblet cells, subepithelial fibrosis, proliferation and migration of airway smooth muscle cells, and epithelial-mesenchymal transition. These complex pathological changes significantly increase airway resistance and responsiveness, forming an important pathological basis for refractory asthma. Currently, the regulatory mechanisms of airway remodeling focus on signaling pathways and regulatory targets. The signaling pathways include phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor-κB(NF-κB), transforming growth factor-β1(TGF-β1)/Smads, and mitogen-activated protein kinase(MAPK). The regulatory targets include microRNAs(miRNAs), competing endogenous RNAs(ceRNAs), long non-coding RNAs(lncRNAs), and circular RNAs(circRNAs). Key proteins involved in these processes include TGF-β1, silencing information regulator 2-related enzyme 1(SIRT1), chitinase 3-like protein 1(YKL-40), and adenosine deaminase-metalloproteinase 33(ADAM33). In recent years, the potential of traditional Chinese medicine in the treatment of asthma has become increasingly evident. Its active ingredients, extracts, and complexes can inhibit airway remodeling in asthma through multiple pathways, demonstrating a variety of effects, including anti-inflammatory actions, inhibition of smooth muscle cell proliferation and migration, regulation of epithelial-mesenchymal transition, attenuation of fibrosis and basement membrane thickening, reduction of mucus secretion, inhibition of vascular remodeling, modulation of immune imbalance, and antioxidative stress. This paper aims to provide an in-depth analysis of the pathogenesis and therapeutic targets of asthma, offering theoretical support and innovative strategies for clinical research and drug development in the treatment of asthma.
Asthma/pathology* ; Humans ; Airway Remodeling/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; Transforming Growth Factor beta1/metabolism*

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

To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.

To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.