1.Mechanism of Ruyan Neixiao Cream in Promoting Ferroptosis in Breast Precancerous Lesion Cells by Regulating Nrf2/SLC7A11/GPX4 Signaling Pathway
Haotian ZHANG ; Yebei QIU ; Ran SU ; Xianxin YAN ; Min MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):98-107
ObjectiveTo explore the mechanism by which Ruyan Neixiao cream (RUC) induces ferroptosis in breast precancerous lesion (BPL) cells, and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%, 2%, and 4% concentrations of Ruyanneixiao Cream transdermal solution (RUT) was assessed using cell counting kit-8 (CCK-8) and a colony formation assay. Reactive oxygen species (ROS) were measured using the DCFH-DA probe, and the levels of ferrous ions (Fe2+), glutathione (GSH), and malondialdehyde (MDA) were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY581/591 fluorescent probe. The expression of nuclear factor E2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) proteins was analyzed by Western blot. The BPL rat model was constructed using 2,2′-bis(hydroxymethyl)butyric acid (DMBA) combined with estrogen and progesterone, and the rats were treated with RUC for external application. After the 12th cycle, the rats were euthanized, and histopathological changes in breast tissue were observed by hematoxylin-eosin (HE) staining. Fe2+ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2, SLC7A11, and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry (IHC) and Western blot. ResultsCompared with the matrix group, the cell viability of MCF-10AT cells in the 1%, 2%, and 4% RUT groups was significantly reduced (P<0.05) in a concentration-dependent manner, with the 24-hour half inhibitory concentration (IC50) being 2.23%. Compared with the 4% RUT group, cell viability in the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the colony formation rates of MCF-10AT cells in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the cell colony formation rate of the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the levels of ROS and Fe2+ in the 1%, 2%, and 4% RUT groups were significantly increased (P<0.05), while GSH levels were significantly decreased (P<0.05), and MDA and lipid peroxidation levels were significantly increased (P<0.05). Compared with the 4% RUT group, ROS and Fe2+ levels in the RUT + Fer-1 group were significantly reduced (P<0.05), while GSH levels were significantly increased (P<0.05), and MDA and lipid peroxidation levels were significantly reduced (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the RUT + Fer-1 group were significantly increased (P<0.05). In the in vivo experiment, compared with the matrix group, the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved, with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group, Fe2+ and MDA levels in the mammary tissue of the RUC group were significantly increased (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the mammary tissue of the RUC group were significantly reduced (P<0.05). ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway, increasing Fe2+ accumulation, and promoting lipid peroxidation.
2.Yttrium-90 selective internal radiation therapy on liver cancer: the past, the present, and the future
Jingqin MA ; Linhong ZHANG ; Minjie YANG ; Jiabin CAI ; Ying FANG ; Rong LIU ; Xudong QU ; Lingxiao LIU ; Zhiping YAN
Chinese Journal of Clinical Medicine 2025;32(1):3-8
Yttrium-90 selective internal radiation therapy (90Y-SIRT) is a treatment technique that delivers radioactive microspheres precisely to the arterial vascular bed of neoplasms, utilizing beta radiation to administer a high local dose of radiation to the neoplasm tissues. This technology has demonstrated significant efficacy in patients with unresectable pirmary liver cancers and liver metastases. This article systematically reviews the development history and clinical application status of 90Y-SIRT in the treatment of liver cancer, and looks forward to future development directions.
3.Advances in the diagnosis and treatment of hepatocellular carcinoma with bile duct tumor thrombus
Yuxiang GUO ; Maosen WANG ; Zhongyuan LIU ; Xudong ZHANG ; Pengfei MA ; Xiangkun WANG ; Renfeng LI
Journal of Clinical Hepatology 2025;41(2):359-364
Hepatocellular carcinoma (HCC) with biliary duct tumor thrombus (BDTT) is currently not common in clinical practice and is easily misdiagnosed, and previously, it was often considered an advanced stage of the disease with a poor prognosis, making its treatment challenging. However, in-depth studies in recent years have gradually deepened our understanding of this disease, leading to significant changes in diagnostic and treatment concepts. Currently, comprehensive treatment, mainly surgery, is used for treatment, but there is still controversy over the selection of clinical treatment strategies. This article provides a detailed discussion on surgical methods and prognosis, in order to provide a reference for clinical treatment options.
4.Clinical practice guidelines for intraoperative cell salvage in patients with malignant tumors
Changtai ZHU ; Ling LI ; Zhiqiang LI ; Xinjian WAN ; Shiyao CHEN ; Jian PAN ; Yi ZHANG ; Xiang REN ; Kun HAN ; Feng ZOU ; Aiqing WEN ; Ruiming RONG ; Rong XIA ; Baohua QIAN ; Xin MA
Chinese Journal of Blood Transfusion 2025;38(2):149-167
Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.
5.Effect of Yifei Jianpi Prescription on Lipopolysaccharide-induced Lung Immune Inflammatory Response in Rats Based on STAT1/IRF3 Pathway
Hongjuan YANG ; Yaru YANG ; Yujie YANG ; Zhongbo ZHU ; Quan MA ; Yanlin WU ; Hongmei LI ; Xuhui ZHANG ; Xiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):146-155
ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 (STAT1)/interferon regulatory factor 3 (IRF3) signaling pathway in a pneumonia model induced by lipopolysaccharide (LPS) and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group, and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling, the rats were randomly divided into the model group, dexamethasone group (0.5 mg·kg-1), and Yifei Jianpi prescription high-dose (12 mg·kg-1), medium-dose (6 mg·kg-1), and low-dose (3 mg·kg-1) groups, with 10 rats in each group. Treatment was administered once daily, and the normal control and model groups received the same volume of normal saline. After 14 days, flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and the content of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) in alveolar lavage fluid (BALF). Hematoxylin-eosin (HE) staining was used to observe lung tissue pathology and score the damage. Thymus weight, spleen weight, and wet-to-dry weight ratio (W/D) were recorded. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT1, IRF3, IL-6, and interferon-alpha (IFN-α) in lung tissues, while Western blot was performed to assess the protein expression of STAT1, IRF3, IL-6, and IFN-α. ResultsCompared with the normal control group, the model group showed significantly increased proportion of B lymphocytes in peripheral blood, decreased proportions of NK cells and CD4+/CD8+ (P<0.05, P<0.01), decreased serum levels of IgG and IgA, significantly increased IgM levels (P<0.01), significantly elevated content of TNF-α, IL-6, and IL-8 in BALF, and significantly decreased IL-10 levels (P<0.01). Lung tissue damage was evident, with significant increases in thymus and spleen weights and a higher W/D ratio (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly upregulated (P<0.05,P<0.01). Compared with the model group, the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood, increased proportions of NK cells and CD4+/CD8+ ratios (P<0.05, P<0.01), significantly increased serum levels of IgG and IgA, significantly decreased IgM levels (P<0.05, P<0.01), significantly reduced levels of TNF-α, IL-6, and IL-8 in BALF, and significantly increased IL-10 levels (P<0.01). Lung tissue damage was alleviated, thymus and spleen weights were significantly reduced, and the W/D ratio was markedly decreased (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly downregulated (P<0.05, P<0.01). ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.
6.Clinical research on corneal epithelium remodeling after small incision lenticule extraction and femtosecond laser-assisted in situ keratomileusis
Yangjing ZHANG ; Liwei MA ; Fan ZHANG ; Chunmei KE ; Ruifu WANG ; Lipye ZU
International Eye Science 2025;25(1):37-41
AIM: To compare the changes in corneal epithelial thickness(CET)after small incision lenticule extraction(SMILE)and femtosecond laser-assisted in situ keratomileusis(FS-LASIK).METHODS: A total of 187 patients(187 eyes)who underwent either SMILE or FS-LASIK at Urumqi Aier Eye Hospital between December 2022 and November 2023 were collected. The patients were divided into SMILE group and FS-LASIK group according to surgical methods. The CET of the patients was measured by optical coherence tomography(OCT)system before surgery and at 1 wk, 1, 3, and 6 mo postoperatively.RESULTS: Changes in corneal epithelial thickness(△CET)in the central, paracentral, and mid-peripheral regions were compared at 6 mo postoperatively. The SMILE group was characterized by the most significant thickening in the central area and the least thickening in the mid-peripheral area; while the FS-LASIK group was characterized by the most significant thickening in the paracentral area and the least thickening in the mid-peripheral region. At 1 wk, 1, 3, and 6 mo postoperatively, within the 0-7 mm corneal area, the △CET for both the SMILE and FS-LASIK groups was correlated with the preoperative spherical equivalent.CONCLUSION: Within 6 mo postoperatively, both SMILE and FS-LASIK showed a similar trend in epithelial thickening but with distinct characteristics. The change in corneal epithelial thickness for both procedures was positively correlated with the preoperative diopter.
7.Proteomics combined with bioinformatics analysis of protein markers of dry eye
Yanting YANG ; Yajun SHI ; Guang YANG ; Haiyang JI ; Jie LIU ; Jue HONG ; Dan ZHANG ; Xiaopeng MA
International Eye Science 2025;25(1):104-111
AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.
8.Analysis of Quality Uniformity of Hengzhi Kechuan Capsules Based on HPLC-DAD-CAD
Qian MA ; An LIU ; Qingxia XU ; Cong GUO ; Jun ZHANG ; Maoqing WANG ; Xiaodi KOU ; Yan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):168-174
ObjectiveTo establish the fingerprints of 15 batches of Hengzhi Kechuan capsules, to quantitatively analyze 10 index components, and to evaluate the quality uniformity of samples from different batches. MethodsThe fingerprints and quantitative analysis of Hengzhi Kechuan capsules were established by a combination method of high performance liquid chromatography coupled with diode array detector and charged aerosol detector(HPLC-DAD-CAD), adenosine, guanosine, vanillic acid, safflomin A, agarotetrol, naringin, hesperidin, militarine, ginsenoside Rb1, and glycyrrhizic acid were selected as quality attribute indexes. A total of 15 batches of Hengzhi Kechuan capsules from 2022 to 2024(3 boxes per batch) were qualitatively and quantitatively analyzed, and the quality uniformity level of the manufacturers was characterized by parameters of intra-batch consistency(PA) and inter-batch consistency(PB). The homogeneity and difference of quality attribute indexes of samples from different years were analyzed by heatmap clustering analysis. ResultsHPLC fingerprints and quantitative method of Hengzhi Kechuan capsules were established, and the methods could be used for qualitative and quantitative analysis of this preparation, which was found to be stable and reliable by method validation. The similarity of fingerprints of 15 batches of samples was 0.887-0.975, a total of 13 common peaks were calibrated, and 10 common peaks were designated, all of which were quality attribute index components. The results of quantitative analysis showed that the contents of the above 10 ingredients in the samples were 0.038-0.078, 0.115-0.251, 0.007-0.018, 0.291-0.673, 0.122-0.257, 0.887-1.905, 1.841-3.364, 1.412-2.450, 2.207-3.112, 0.650-1.161, respectively. And the contents of ginsenoside Rb1 and glycyrrhizic acid met the limit requirements in the 2020 edition of Chinese Pharmacopoeia. For the samples from 15 batches, the PA values of the 10 index components were all <10%, indicating good intra-batch homogeneity, and the PB values ranged from 33.86% to 92.97%, suggesting that the inter-batch homogeneity was poor. Heatmap clustering analysis showed that the samples from different years were clustered into separate categories, and adenosine, guanosine, safflomin A, naringin, hesperidin and agarotetrol were the main differential components. ConclusionThe intra-annual quality uniformity of Hengzhi Kechuan capsules is good and the inter-annual quality uniformity is insufficient, which may be related to the quality difference of Pinellinae Rhizoma Praeparatum, Carthami Flos, Citri Sarcodactylis Fructus, Citri Reticulatae Pericarpium, Aquilariae Lignum Resinatum, Citri Fructus, etc. In this study, the fingerprint and multi-indicator determination method of Hengzhi Kechuan capsules was established, which can be used for more accurate and efficient quality control and standardization enhancement.
9.Signaling Pathways Related to Polycystic Ovary Syndrome and Regulation by Traditional Chinese Medicine: A Review
Manman YAO ; Liya MA ; Dawei ZHANG ; Xuelin ZHANG ; Xuan ZHOU ; Yu TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):301-312
Polycystic ovary syndrome (PCOS) is one of the most prevalent gynecological diseases, and its incidence is increasing year by year, seriously affecting the physical and mental health of female patients. The pathogenesis of this disease is complex and has not been fully clarified. At present, PCOS is mainly treated by Western medicine, which, however, has poor efficacy and induces various adverse reactions. Therefore, developing safe and effective therapies has become a difficult problem that needs to be solved. Studies have confirmed that traditional Chinese medicine (TCM) can regulate phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB), transforming growth factor-β (TGF-β)/Smads, secreted glycoprotein/β-catenin (Wnt/β-catenin), adenosine monophosphate-activated protein kinase (AMPK), and advanced glycation endproduct/receptor for advanced glycation endproducts (AGE/RAGE) signaling pathways to ameliorate insulin resistance, inhibit inflammation and oxidative stress, regulate endocrine hormone disorders, and intervene in apoptosis and autophagy, thus alleviating the symptoms, slowing down the disease progression, and improving the ovarian function. The treatment of PCOS with TCM has demonstrated definite effects and high safety. Therefore, exploring this disease from cellular and molecular perspectives can provide a theoretical basis for its clinical treatment and new drug development. However, there is a lack of systematic reviews on the modulation of relevant signaling pathways by TCM in the treatment of PCOS. This article reviews the research progress in the treatment of PCOS with the active ingredients and compound prescriptions of TCM by regulating relevant signaling pathways in recent years, with the aim of providing evidence to support the promotion of TCM for treating PCOS in the future.
10.Chinese Medicine Regulates JAK2/STAT3 Signaling Pathway to Treat Ovarian Cancer: A Review
Yue ZHANG ; Danni DING ; Jia LI ; Wenwen MA ; Fengjuan HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):323-330
Ovarian cancer (OC) is one of the most common malignant tumors in women, with the mortality rate being the highest among gynaecological malignant tumors. As the atypical symptoms of OC are difficult to be detected in the early stage, most patients are already in the advanced stage when being diagnosed. As a result, the clinical treatment has limited effects. Currently, the main therapies for OC are surgery and chemotherapy, while their drug resistance and adverse reactions seriously reduce the quality of life of patients. In recent years, traditional Chinese medicine (TCM) has attracted the attention of clinicians and researchers because of its high efficacy, low toxicity, and mild side effects. According to the TCM philosophy of treatment based on syndrome differentiation, the Chinese medicines with multiple targets, wide range, and mild side effects can be screened based on the molecular targets involved in the occurrence and development of OC, which can bring out the unique advantages of TCM in the treatment of OC. Modern studies have shown that the occurrence and development of OC are closely related to the abnormal expression of multiple signaling pathways. The continued abnormal activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway can lead to abnormal proliferation and malignancy of OC. cause abnormal proliferation and malignant transformation of OC, which is closely related to the development of OC. In addition, studies have shown that Chinese medicine can inhibit the proliferation, angiogenesis, invasion, and metastasis and promote the autophagy and apoptosis of OC cells by regulating the Janus kinase 2 (JAK2)/STAT3 signaling pathway, providing new therapeutic strategies and ideas for the prevention and treatment of OC. This paper summarizes the role of JAK2/STAT3 signaling pathway in OC development by reviewing the relevant articles and reviews the mechanism and research progress of active components and compound prescriptions of Chinese medicine intervening in OC development by regulating the JAK2/STAT3 signaling pathway. This review is expected to provide a systematic reference for clinical research and drug development of OC.

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