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: Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. METHODS: HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. RESULTS: Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. CONCLUSION Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis. Please cite this article as: Feng CY, Cai CS, Shi XQ, Zhang ZJ, Su D, Qiu YQ. Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma. J Integr Med. 2025; 23(1): 79-91.
Humans ; MicroRNAs/genetics* ; Liver Neoplasms/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Mitophagy/drug effects* ; Resveratrol/pharmacology* ; Animals ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Hep G2 Cells ; Mice ; Disease Progression ; Mice, Inbred BALB C

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Ophiopogon japonicus, a precious medicinal plant endemic to Zhejiang Province. Its tuberous roots are rich in bioactive components such as flavonoids, possessing anti-inflammatory, antioxidant, and immunomodulatory properties. To elucidate the impact of cadmium (Cd) stress on the accumulation and biosynthetic pathway of flavonoids in O. japonicus, this study exposed O. japonicus to different concentrations of Cd stress and explored the changes through integrated transcriptomics and metabolomics analysis. The results demonstrated that Cd stress (1 mg/L and 10 mg/L) significantly increased the content of flavonoids in O. japonicus in a concentration-dependent manner. The metabolomics analysis revealed a total of 110 flavonoids including flavones, flavanols, flavonols, flavone and flavonol derivatives, flavanones, isoflavonoids, chalcones and dihydrochalcones, and anthocyanins in O. japonicus, among which flavones, flavonols, flavone and flavonol derivatives, and anthocyanins increased under Cd stress. The transcriptomics analysis identified several key flavonoid biosynthesis-associated genes with up-regulated expression under Cd stress, including 14 genes encoding 4-coumarate CoA ligase (4CL), 2 genes encoding chalcone isomerase (CHI), and 14 genes encoding phenylalanine ammonia lyase (PAL). The gene-metabolite regulatory network indicated significant positive correlations of 4CL (Cluster-21637.5012, Cluster-21637.90648, and Cluster-21637.62637) and CHI (Cluster-21637.111909 and Cluster-21637.123300) with flavonoid metabolites, suggesting that these genes promoted the synthesis of specific flavonoid metabolites, which led to the accumulation of total flavonoids under Cd stress. These findings provide theoretical support for the cultivation and utilization of medicinal plants in Cd-contaminated environments and offered new perspectives for studying plant responses to heavy metal stress.
Cadmium/toxicity* ; Flavonoids/biosynthesis* ; Metabolomics ; Ophiopogon/drug effects* ; Stress, Physiological ; Transcriptome ; Gene Expression Profiling ; Gene Expression Regulation, Plant

Traditionally, platelets, which are anucleate cell fragments derived from blood cells, have been primarily associated with their pivotal functions in hemostasis and thrombosis. However, recent research has elucidated their significant role in immune regulation, highlighting their expression of various immune receptors, involvement in numerous immune-related signaling pathways, and activation of diverse effector functions. This paper elaborates on the fundamental biological characteristics and immune functions of platelets, the involvement of activated platelets in immune regulation, and their prospective applications in clinical therapy. Furthermore, the paper discusses future directions in platelet immune research, as well as the prospects and developmental trends in immunotherapy, aiming to furnish a thorough reference for the investigation and clinical utilization of platelets within the domain of immune regulation.

Objective To investigate the effects of Phellinus baumii polyphenol(PBP)on head and neck squamous cell carcinoma(HNSCC)and analyze the potential mechanism based on network pharmacology and in vitro experiments.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),DrugBank,GeneCards,Comparative Toxicogenomics Database(CTD)and Online Mendelian Inheritance in Man(OMIM)database were used to screen the active components of PBP and potential targets of PBP on HNSCC.The potential target interaction network was constructed using String database,and the core targets were screened by two-step topology analysis.Enrichment analysis of potential targets was performed using the DAVID database.Human HNSCC cell lines SCC-15 and SCC-25 were cultured in vitro using PBP intervention of 0,25,50 mg/L,respectively.The cell proliferation and colony formation ability were detected by cell counting reagent(CCK-8)and colony formation assay.Western blot assay was used to detect the expression of PBP core target protein in 2 cell lines.Results A total of 280 targets were identified for 17 active components of PBP,264 of which were HNSCC-related genes.Two-step topology analysis showed that hypoxia inducible factor 1 subunit alpha(HIF1A),tumor protein p53(TP53),AKT serine/threonine kinase 1(AKT1),signal transducer and activator of transcription 3(STAT3),cyclin A2(CCNA2)and JUN proto-oncogene(JUN)were the core targets.The enrichment results suggested that PBP may play a role in HNSCC through various pathways.In vitro experiment results showed that with the increase of PBP intervention concentration,the proliferation ability and colony formation ability of SCC-15 and SCC-25 cells were significantly decreased(P＜0.05),while the protein expression levels of STAT3,AKT1 and CCNA2 were decreased(P＜0.05).Conclusion PBP can inhibit the progression of HNSCC by multi-target and multi-pathway.

Objective:To investigate the impact of correcting rotational subluxation through circumferential fusion and transforaminal lumbar interbody fusion (TLIF) on postoperative coronal plane imbalance in degenerative scoliosis.Methods:A retrospective analysis was conducted on the data of 108 patients with type A degenerative scoliosis in the Nanjing classification who underwent primary multi-segment posterior column osteotomy (PCO) with deformity correction and internal fixation at Nanjing Gulou Hospital from June 2017 to June 2021. Patients were divided into two groups based on the presence of preoperative rotational subluxation: the rotational subluxation group and the non-rotational subluxation group. The rotational subluxation group consisted of 60 patients, with 8 males and 52 females, aged 63.7±5.5 years (range, 56-75 years). The non-rotational subluxation group included 48 patients, with 5 males and 43 females, aged 64.4±5.2 years (range, 53-72 years). Within the rotational subluxation group, depending on whether TLIF was performed on the rotational subluxation segment, they were further categorized into the TLIF group and the PCO group. The TLIF group comprised 28 patients, while the PCO group had 32 patients. Full-spine anteroposterior and lateral X-rays were taken preoperatively, postoperatively, and at the last follow-up to measure coronal balance types and radiographic parameters. The differences in the lumbar Cobb angle, coronal balance distance (CBD), and the Cobb angle of the lumbosacral curve (Cobb-Fra angle) were compared between the rotational subluxation group and the non-rotational subluxation group, as well as between the TLIF group and the PCO group.Results:The average surgery duration ranged from 200 to 310 min, with a mean of 235±47 min. The intraoperative blood loss ranged from 700 to 2,400 ml, with an average of 950±355 ml. The number of fused segments in the rotational subluxation group was 7.6±2.1, ranging from 5 to 11 segments, while in the non-rotational subluxation group, it was 7.4±2.0, ranging from 5 to 10 segments. Postoperatively, 13%(8/60) of patients in the rotational subluxation group developed type C coronal imbalance, significantly higher than the 2%(1/48) in the non-rotational subluxation group. The immediate postoperative and final follow-up lumbar Cobb angles, CBD, and Cobb-Fra angles in the rotational subluxation group were 20.60°±10.73° and 20.33°±10.92°, 22.53±16.45 mm and 18.53±17.31 mm, 13.14°±4.40° and 11.23°±4.92°, respectively, which were higher than those in the non-rotational subluxation group (13.92°±7.02° and 12.92°±6.64°, 18.62±17.44 mm and 8.83±8.95 mm, 11.91°±3.03° and 9.52°±3.30°), with statistical significance ( P<0.05).. Among patients in the rotational subluxation group, the probability of new-onset coronal imbalance postoperatively was 4%(1/28) in the TLIF group, which was lower than the 22%(7/32) in the PCO group, with a statistically significant difference (χ 2=4.330, P=0.037). The immediate postoperative and final follow-up lumbar Cobb angles, CBD, and Cobb-Fra angles in the PCO group were 25.63°±11.00° and 25.13°±11.04°, 27.37±18.95 mm and 25.25±18.67 mm, 15.50°±3.62° and 14.08°±4.77°, respectively, which were significantly higher than those in the TLIF group (14.86°±6.96° and 14.86°±5.37°, 17.08±10.94 mm and 10.86±7.86 mm, 10.14°±3.37° and 8.46°±2.66°), with statistical significance ( P<0.05). Conclusion:For patients with Type A degenerative scoliosis combined with rotational subluxation according to the Nanjing classification, performing a 360-degree circumferential release and interbody fusion at the segment with rotatory subluxation can reduce the risk of developing new postoperative coronal imbalances.

Objective:To evaluate the mediating effect of electrocardiographic (ECG) indicators in the association between short-term exposure to fine particulate matter (PM 2.5) and blood pressure and to explore the key PM 2.5 element constituents that produce the mediating effect. Methods:Based on a cross-sectional survey across 10 cities in the Beijing-Tianjin-Hebei region and surrounding areas, PM 2.5 and its element constituents were collected from the nearest air monitoring superstation. Blood pressure and ECG indicators of participants were obtained through physical examinations. A multivariate linear regression was used to evaluate the effect of short-term exposures to PM 2.5 on blood pressure. A mediation analysis was used to identify the mediating effect of ECG indicators in the association between exposure to PM 2.5 and its element constituents and blood pressure. Results:The age of the 1 793 participants was (65.1±13.3) years, and 885 (49.4%) were males. During the study period, the daily mean concentration of PM 2.5 was (70±45) μg/m 3, and the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were (139±20), (82±11), (101±13), and (57±17) mmHg (1 mmHg=0.133 kPa), respectively. The results of the multivariate linear regression showed that for every 10 μg/m 3 increase in PM 2.5 on the same day (lag 0), DBP increased by 0.15 (95% CI: 0.02-0.28) mmHg, and PP decreased 0.18 (95% CI: 0.36-0.01) mmHg. The exposure to 14 elemental constituents, such as Ga, Co and Se, was associated with an increase in DBP, while the exposure to 17 elemental constituents, such as Cs, Se and Ag, was associated with a decrease in PP. At lag 0, the PM 2.5-induced increase in DBP was mediated by the QRS interval (mediation percentage of 18.98%), and the PM 2.5-induced decrease in PP was mediated by the QT interval (mediation percentage of -6.31%). The exposure to K, Br, Pb, Zn, Ca, Co, Pd, Cu, and As constituents was associated with increases in DBP mediated by prolonged QRS interval. The exposure to Pb, Zn, K, and As constituents was associated with decreases in PP mediated by prolonged QRS interval. Conclusion:ECG indicators such as QRS interval may mediate the association between short-term exposure to PM 2.5 and its element constituents and blood pressure.