Hepatocellular carcinoma（HCC）， as one of the common malignant tumours， has seen a continuous rise in incidence and mortality worldwide， posing a serious threat to human health. However， traditional treatments have certain limitations， therefore， the exploration of new therapeutic strategies is particularly urgent. In recent years， with in-depth research on the regulatory mechanisms of microRNA（miRNA） in tumour occurrence and development， it has become new targets for HCC diagnosis and treatment. As a traditional treatment method， Chinese medicine， due to its multi-component， multi-pathway， and multi-target overall regulatory characteristics， shows broad prospects in treating HCC by regulating miRNAs. Accordingly， this paper reviews recent studies on the role of miRNAs in HCC and research advances in traditional Chinese medicine interventions， finding that various miRNAs play key roles in HCC cell cycle regulation， proliferation and apoptosis， invasion and metastasis， immune microenvironment， and drug resistance. It summarises how active ingredients， extracts， medicinal pairs， and formulas of Chinese medicine act on specific miRNAs to regulate their downstream target gene expression， affecting the malignant behaviour of HCC cells and exerting anti-cancer effects. This study aims to provide a theoretical basis for miRNAs as potential biomarkers and therapeutic targets for HCC， as well as to offer new ideas for developing miRNA-based targeted Chinese medicine therapies.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

ObjectiveAngelicae Sinensis Radix， a commonly used medicinal herb with both medicinal and edible properties， is frequently adulterated in the market， severely affecting the clinical efficacy of preparations. While qualitative identification techniques for adulterants and counterfeits are now relatively mature， quantitative detection methods for adulterated processed products remain unexplored. Quantitative detection research of Angelicae Sinensis Radix and its primary closely related adulterant， "Tu Danggui" （Angelica gigas）， was conducted to establish a herbal quantitative molecular detection （Herb-Q） method for Angelicae Sinensis Radix and its processed products， providing a model for the establishment of quantitative detection technologies for Angelicae Sinensis Radix and related health products. MethodsThe specific single-nucleotide polymorphism （SNP） loci of Angelicae Sinensis Radix and Angelica gigas Nakai were screened based on the complete chloroplast genome sequence. The specific SNP loci of Angelicae Sinensis Radix were selected for quantitative methodological investigations （linearity， limit of quantification， limit of detection， and reproducibility） by mixing the powder of the herbs with different adulteration ratios. Huoxue Zhitong powder with three distinct adulteration ratios （15%， 25%， and 35%） was utilized to ascertain the precision of the Herb-Q method for the quantitative detection of Chinese patent medicines containing Angelicae Sinensis Radix. ResultsBy comparing the 123 chloroplast genome sequences of Angelicae Sinensis Radix， based on the principles of intraspecies conservation， interspecies specificity， and meeting the requirements of pyrophosphate high-throughput sequencing， it was determined that 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 and 38 592^nd locus （T/C） in the chloroplast genome sequence NC_029393.1 could be the exclusive molecular identification loci of Angelicae Sinensis Radix and Angelica gigas Nakai， respectively. The linear relationship R² of the Herb-Q method established by selecting the specific 9 674^th locus （A/G） of Angelicae Sinensis Radix was 0.997 4 （R²>0.99）， indicating an excellent linear relationship. The limits of quantification and detection were established at 2.0%， exhibiting excellent reproducibility ［relative standard deviation（RSD）<2.0%］. The established quantitative system based on the Herb-Q method detected the adulteration amount of counterfeit A. gigas in the Huoxue Zhitong powder， with an average deviation of 1.3% for three molecular quantitative replicates. ConclusionThis research demonstrates that the Herb-Q quantitative detection method established based on the 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 of Angelicae Sinensis Radix has good applicability， objectivity， and accuracy for Angelicae Sinensis Radix and A. gigas， and its processed products. This method has the capacity to provide technical support for the quantitative detection of commercially available Angelicae Sinensis Radix derivatives， including traditional Chinese medicinal preparations， dietary supplements， and nutraceuticals.

ObjectiveAngelicae Sinensis Radix， a commonly used medicinal herb with both medicinal and edible properties， is frequently adulterated in the market， severely affecting the clinical efficacy of preparations. While qualitative identification techniques for adulterants and counterfeits are now relatively mature， quantitative detection methods for adulterated processed products remain unexplored. Quantitative detection research of Angelicae Sinensis Radix and its primary closely related adulterant， "Tu Danggui" （Angelica gigas）， was conducted to establish a herbal quantitative molecular detection （Herb-Q） method for Angelicae Sinensis Radix and its processed products， providing a model for the establishment of quantitative detection technologies for Angelicae Sinensis Radix and related health products. MethodsThe specific single-nucleotide polymorphism （SNP） loci of Angelicae Sinensis Radix and Angelica gigas Nakai were screened based on the complete chloroplast genome sequence. The specific SNP loci of Angelicae Sinensis Radix were selected for quantitative methodological investigations （linearity， limit of quantification， limit of detection， and reproducibility） by mixing the powder of the herbs with different adulteration ratios. Huoxue Zhitong powder with three distinct adulteration ratios （15%， 25%， and 35%） was utilized to ascertain the precision of the Herb-Q method for the quantitative detection of Chinese patent medicines containing Angelicae Sinensis Radix. ResultsBy comparing the 123 chloroplast genome sequences of Angelicae Sinensis Radix， based on the principles of intraspecies conservation， interspecies specificity， and meeting the requirements of pyrophosphate high-throughput sequencing， it was determined that 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 and 38 592^nd locus （T/C） in the chloroplast genome sequence NC_029393.1 could be the exclusive molecular identification loci of Angelicae Sinensis Radix and Angelica gigas Nakai， respectively. The linear relationship R² of the Herb-Q method established by selecting the specific 9 674^th locus （A/G） of Angelicae Sinensis Radix was 0.997 4 （R²>0.99）， indicating an excellent linear relationship. The limits of quantification and detection were established at 2.0%， exhibiting excellent reproducibility ［relative standard deviation（RSD）<2.0%］. The established quantitative system based on the Herb-Q method detected the adulteration amount of counterfeit A. gigas in the Huoxue Zhitong powder， with an average deviation of 1.3% for three molecular quantitative replicates. ConclusionThis research demonstrates that the Herb-Q quantitative detection method established based on the 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 of Angelicae Sinensis Radix has good applicability， objectivity， and accuracy for Angelicae Sinensis Radix and A. gigas， and its processed products. This method has the capacity to provide technical support for the quantitative detection of commercially available Angelicae Sinensis Radix derivatives， including traditional Chinese medicinal preparations， dietary supplements， and nutraceuticals.

ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy （DCM） of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group （186 cases） and non-exposure group （185 cases） according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months， and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events （MACE） in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE， and subgroup analysis was performed. Changes in traditional Chinese medicine （TCM） syndrome score， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVEDD）， and Minnesota Living with Heart Failure Questionnaire （MLHFQ） score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy （before treatment） and 1 year after receiving the therapy （after treatment）. ResultsMACE occurred in 31 cases （16.67%） in the exposure group and 47 cases （25.41%） in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group ［HR=0.559， 95%CI（0.361，0.895）， P=0.014］. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients ［HR=0.623， 95%CI（0.396，0.980）， P=0.041］， and consistent results were observed in different subgroups. Compared with pre-treatment， the exposure group showed decreased TCM syndrome score and MLHFQ score， reduced LVEDD， and increased LVEF and LVFS after treatment （P＜0.05）； in the non-exposure group， TCM syndrome score decreased， LVEF and LVFS increased， and LVEDD reduced after treatment （P＜0.05）. After treatment， the exposure group had higher LVEF and LVFS， smaller LVEDD， and lower TCM syndrome score and MLHFQ score compared with the non-exposure group （P＜0.05）. ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome， meanwhile improving their clinical symptoms， cardiac function， and quality of life.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Residual inflammatory risk （RIR） is a key issue to be urgently addressed in the secondary prevention of atherosclerotic cardiovascular disease （ASCVD）. Targeted intervention of RIR has become a novel target for drug development and clinical management. A series of high-quality randomized controlled trials （RCTs）， including COLCOT， LoDoCo2 and CLEAR SYNERGY， provided high-level evidence and confirmed that low-dose colchicine （0.5 mg/d） significantly reduced the risk of cardiovascular events in ASCVD patients at stable stage or after the acute phase， while its efficacy varied in different clinical scenarios. International authoritative guidelines from the European Society of Cardiology and the American Heart Association/American College of Cardiology include low-dose colchicine in the recommendations for ASCVD secondary prevention. Two domestic guidelines released in 2024， namely the Guideline for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndrome （ 2024 ） and the Guideline for the Diagnosis and Management of Chronic Coronary Syndrome in China ， have also added relevant recommendations. Nevertheless， due to potential racial differences， safety concerns regarding drug-drug interactions， and the relative lack of clinical evidence in China， especially the absence of prospective RCTs using low-dose colchicine for secondary prevention of ASCVD patients， current clinical recommendations still mainly based on international evidence and guidelines， and should not be simply extrapolated.

ObjectiveTreadmill exercise intervention was evaluated for its effects on addictive behavior, learning and memory, and hippocampal neuroinflammation in methamphetamine (MA)-addicted mice, and transcriptomic screening was performed to identify candidate molecules involved in exercise-mediated attenuation of MA-related neuronal injury. MethodsTwo-month-old male C57BL/6 mice were randomly assigned to four groups: control (C), exercise control (CE), methamphetamine (M), and methamphetamine plus exercise (ME). Mice in the M and ME groups received intraperitoneal injections of MA (1 mg/kg) once daily for 7 consecutive days to establish the addiction model, whereas mice in the C and CE groups received equal volumes of saline. Subsequently, mice in the CE and ME groups underwent treadmill exercise at 12 m/min for 60 min/d for 2 weeks. Conditioned place preference (CPP), the Y-maze, and the Morris water maze (MWM) were used to assess addictive behavior, spatial recognition memory, and spatial learning and memory, respectively. Hippocampal neuronal ultrastructure was examined by transmission electron microscopy (TEM), and microglia-related responses were evaluated by immunofluorescence staining for ionized calcium-binding adapter molecule 1 (Iba-1) in the hippocampal CA1 region. Previously generated and publicly available RNA-seq data from brain tissue of the C, M, and ME groups were reanalyzed, with three biological samples per group. Differentially expressed genes (DEGs) were re-screened using the criteria of P<0.05 and fold change>1.5 or <0.67, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. NLR family CARD domain containing 5 (Nlrc5) was further validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot was used to determine the protein expression of NLRC5, nuclear factor kappa B (NF‑κB), interleukin-1β (IL-1β), postsynaptic density-95 (PSD-95), and synaptophysin. ResultsTreadmill exercise significantly attenuated MA-induced conditioned place preference and improved learning and memory performance in both the Y-maze and MWM tests. Exercise increased exploration time and distance in the novel arm of the Y-maze, shortened escape latency, and increased the number of platform crossings in the MWM. Average swimming speed during the probe trial did not differ significantly among groups, suggesting that the MWM differences were not attributable to obvious differences in swimming performance. TEM revealed that MA exposure induced mitochondrial swelling, disrupted cristae, reduced organelle abundance, and nuclear envelope abnormalities in hippocampal neurons, whereas these ultrastructural changes were alleviated after exercise. Immunofluorescence staining showed that MA increased Iba-1 fluorescence intensity in the hippocampal CA1 region, while treadmill exercise significantly reduced this change. Transcriptomic analysis identified 160 DEGs associated with MA exposure and 58 DEGs associated with exercise intervention, with 9 overlapping DEGs. KEGG enrichment analysis showed that MA-related DEGs were enriched in the NOD-like receptor signaling pathway. Among the overlapping DEGs, Nlrc5, which was downregulated after MA exposure and restored following exercise intervention, was selected as a candidate gene for further validation. RT-qPCR confirmed that treadmill exercise reversed the MA-induced decrease in Nlrc5 mRNA expression. Western blot analysis further showed that treadmill exercise increased NLRC5, PSD-95, and synaptophysin protein expression while reducing NF-κB and IL-1β expression. ConclusionTwo weeks of treadmill exercise attenuated MA-induced conditioned place preference and ameliorated learning and memory impairment, alleviated hippocampal neuroinflammation and neuronal ultrastructural damage, and restored the expression of synapse-related proteins. Transcriptomic screening combined with molecular validation demonstrated that exercise intervention was accompanied by restoration of NLRC5 expression, reduced NF‑κB and IL-1β expression, and increased PSD-95 and synaptophysin expression. These findings suggest that NLRC5 may represent a candidate molecule involved in exercise-mediated amelioration of MA-related neuronal injury. However, the present results mainly demonstrate coordinated changes in NLRC5 expression, inflammatory indicators, and cognitive outcomes rather than a direct causal relationship, and the specific role of NLRC5 requires further functional validation.

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals ; Female ; Mice ; CA1 Region, Hippocampal/metabolism* ; Cell Adhesion Molecules/metabolism* ; CRF Receptor, Type 1/metabolism* ; Memory Disorders/etiology* ; Mice, Inbred C57BL ; Nectins/genetics* ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors* ; Recognition, Psychology/physiology* ; Stress, Psychological/complications*