1.Compound Xishu Granules Inhibit Proliferation of Hepatocellular Carcinoma Cells by Regulating Ferroptosis
Yuan TIAN ; Yuxi WANG ; Zhen LIU ; Yuncheng MA ; Hongyu ZHU ; Xiaozhu WANG ; Qian LI ; Jian GAO ; Weiling WANG ; Wenhui XU ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):37-45
ObjectiveTo study the mechanism of compound Xishu granules (CXG) in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model, Fufang Banmao (0.21 g·kg-1), low-dose (1.87 g·kg-1) CXG, medium-dose (3.74 g·kg-1) CXG, and high-dose (7.49 g·kg-1) CXG groups. Mice were administrated with drinking water or CXG for 28 days, and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 (CCK-8) was used to examine the survival rate of Huh7 cells treated with different concentrations (0, 31.25, 62.5, 125, 250, 500, 1 000 mg·L-1) of CXG for 24 h and 48 h. CA-AM, DCFH-DA, and C11-BODIPY581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion (Fe2+), reactive oxygen species (ROS), and lipid peroxide (LPO), respectively. The colorimetric method was employed to measure the levels of glutathione (GSH) and superoxide dismutase (SOD). Western blot was employed to determine the protein levels of glutathione peroxidase 4 (GPX4), transferrin receptor 1 (TFR1), and ferritin heavy chain 1 (FTH1), respectively. ResultsIn the animal experiment, compared with the model group, the drug treatment groups showed reductions in the tumor volume from day 12 (P<0.01). After treatment, the Fufang Banmao and low-, medium-, and high-dose CXG groups had lower tumor volume, relative tumor volume, and tumor weight than the model group (P<0.05), with tumor inhibition rates of 48.99%, 79.93%, 91.38%, and 97.36%, respectively. Moreover, the CXG groups had lower tumor volume and relative tumor volume (P<0.05 in all the three dose groups) and lower tumor weight (P<0.05 in medium-dose and high-dose groups) than the Fufang Banmao group. Compared with the model group, the drug treatment groups showed reduced number of tumor cells, necrotic foci with karyopyknosis, nuclear fragmentation, and nucleolysis, and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment, compared with the blank group, CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h (P<0.05). Compared with the blank group, the RSL3 group and the low-, medium-, and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY581/591, which indicated elevations in the levels of Fe2+ (P<0.01), ROS (P<0.05), and LPO (P<0.01), respectively. Compared with the blank group, the RSL3 and low-, medium-, and high-dose CXG groups showed lowered levels of GSH and SOD (P<0.05). In addition, the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 (P<0.05), and the low- and high-dose CXG groups presented up-regulated expression of TFR1 (P<0.05). ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe2+and LPO levels.
2.Applications of Vaterite in Drug Loading and Controlled Release
Xiao-Hui SONG ; Ming-Yu PAN ; Jian-Feng XU ; Zheng-Yu HUANG ; Qing PAN ; Qing-Ning LI
Progress in Biochemistry and Biophysics 2025;52(1):162-181
Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.
3.Effect of Biejia Decoction Pill on aerobic glycolysis in hepatocellular carcinoma by regulating the protein kinase B/mammalian target of rapamycin signaling pathway
Qinwen TAN ; Jingjing HUANG ; Ruixi ZHONG ; Yuanqin DU ; Jian XU ; Jinli NONG ; Yujiao PENG
Journal of Clinical Hepatology 2025;41(2):300-306
ObjectiveTo investigate the inhibitory effect of Biejia Decoction Pill on the proliferation, migration, and aerobic glycolysis of hepatocellular carcinoma (HCC) using cell experiments, as well as related mechanisms. MethodsHuman liver cancer cell line Huh7 was selected, and Sprague-Dawley rats were randomly divided into blank serum group, inhibitor group, and high-, middle-, and low-dose Biejia Decoction Pill groups. Rat serum containing the drug was prepared for the incubation of Huh7 cells. CCK8 assay and scratch assay were used to explore the effect of Biejia Decoction Pill on the proliferation and migration of HCC cells; glycolytic rate-limiting enzymes and metabolites were measured to explore the effect of Biejia Decoction Pill on aerobic glycolysis of liver cancer cells; RT-qPCR and Western blot were used to explore the effect of Biejia Decoction Pill on the mRNA expression, related proteins, and phosphorylation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test or the Dunnett’s T3 test were used for further comparison between two groups. ResultsCompared with the blank serum group, the Biejia Decoction Pill groups had significant reductions in OD value, migration rate during different periods of time, glycolytic rate-limiting enzymes (hexokinase, phosphofructokinase, pyruvate kinase), and glycolytic metabolites (pyruvate, lactic acid, ATP) (all P<0.05). RT-qPCR results showed that compared with the blank serum group, the high-, middle-, and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of mTOR, and the high- and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of AKT (all P<0.05). Western blot results showed that compared with the blank serum group, the high-, middle-, and low-dose Biejia Decoction Pill groups had significant reductions in the expression levels of mTOR-related proteins and phosphorylated proteins, and the high- and middle-dose Biejia Decoction Pill groups had significant reductions in the expression levels of AKT-related proteins and phosphorylated proteins (all P<0.05). ConclusionThis study preliminarily verifies that the serum containing Bijia Decoction Pill can inhibit the aerobic glycolysis of human hepatoma Huh7 cells, thereby inhibiting their proliferation and migration, possibly by inhibiting the expression of the proteins related to the AKT/mTOR signaling pathway.
4.Comparison of the clinical efficacy of super pulse thulium laser enucleation of the prostate with "open tunnel" and holmium laser enucleation of the prostate for benign prostatic hyperplasia
Jidong XU ; Ning JIANG ; Jian LI ; Zhikang CAI ; Jianwei LYU ; Chuanyi HU ; Jingcun ZHENG ; Zhonglin CAI ; Huiying CHEN ; Yan GU ; Yuning WANG ; Jiasheng YAN ; Zhong WANG
Journal of Modern Urology 2025;30(1):34-38
[Objective] To compare the clinical efficacy of super pulse thulium laser enucleation of the prostate (SPThuLEP) with "open tunnel" and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH), in order to provide reference for the treatment options of BPH. [Methods] The clinical data of 112 BPH patients treated in our hospital during Jan.2023 and Jul.2023 were retrospectively analyzed, including 65 treated with SPThuLEP with "open tunnel" and 57 with HoLEP.The operation time, postoperative hemoglobin decrease, postoperative bladder irrigation, catheter indwelling time, hospitalization time and complications were compared between the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) and prostate-specific antigen (PSA) were compared between the two groups before operation and one month after operation. [Results] All operations were successful without conversion to open or transurethral plasmakinetic resection.The postoperative decrease of hemoglobin in SPThuLEP group was lower than that in HoLEP group [(13.12±6.72) g/L vs. (21.02±6.51) g/L], with statistical difference (P<0.05). There were no significant differences in the operation time [(63.35±15.73) min vs.(61.02±17.55) min], postoperative bladder irrigation time [(1.07±0.45) d vs. (1.06±0.36) d], catheter indwelling time [(2.98±0.56) d vs. (3.01±0.63) d] and hospitalization time [(3.63±0.61) d vs.(3.79±0.76) d] between the two groups (P>0.05). No blood transfusion, secondary bleeding or unplanned hospitalization occurred, and there were no serious complications such as transurethral electroresection syndrome (TURS), urethral stricture and urinary incontinence.One month after operation, the Qmax, IPSS, QoL, PVR and PSA of the two groups were significantly improved compared with those before operation (P<0.05), but with no statistical difference between the two groups (P>0.05). [Conclusion] SPThuLEP with "open tunnel" has comparable efficacy as HoLEP in the treatment of BPH.With advantages of small amount of bleeding and high safety, this minimally invasive technique can be widely popularized in clinical practice.
5.Factors influencing repeat blood donor lapsing in Guangzhou: based on the zero-inflated poisson regression model
Rongrong KE ; Guiyun XIE ; Xiaoxiao ZHENG ; Yingying XU ; Xiaochun HONG ; Shijie LI ; Yongshi DENG ; Jinyu SHEN ; Jinyan CHEN ; Jian OUYANG
Chinese Journal of Blood Transfusion 2025;38(1):73-78
[Objective] To analyze the influencing factors of repeat blood donor lapsing using a zero-inflated poisson regression model (ZIP). [Methods] The blood donation behavior of 12 498 whole blood donors from 2020 was tracked until December 31, 2023. The factors influencing the frequency of blood donations in a given year was analyzed using ZIP, and donors with 0 blood donation in that year were considered to have lapsed. The changes in relevant influencing factors associated with each blood donation were measured and modeled for analysis. [Results] The zero-inflated part of ZIP showed that the risk of lapsing of male blood donors was 2.24 times that of female blood donors (OR 95% CI:1.864-2.696, P<0.001); the risk of lapsing of the 35-44 age group and over 45 age group was respectively 40% (OR 95% CI:0.455-0.790, P<0.001) and 61%(OR 95% CI:0.268-0.578, P<0.001) lower than that of the under 25 age group; the risk of lapsing for those who have donated blood twice and ≥3 times was respectively 50% (OR 95% CI:0.405-0.609, P<0.001) and 81% (OR 95% CI:0.154-0.225, P<0.001) lower than that of first-time donors; the risk of lapsing of those with junior high or high school education was 1.2 times that of those with a college degree or higher (OR 95% CI:1.033-1.384, P<0.05); the risk of lapsing for the divorced group was 2.02 times that of the married group (OR 95% CI:1.445-2.820, P<0.001); the risk of lapsing for those with an income (Yuan) of 10 000 to 50 000, 50 000 to 100 000 and more than 100 000 was respectively 0.67 (OR 95% CI:0.552-0.818, P<0.001), 0.72 (OR 95% CI:0.591-0.884, P=0.002) and 0.67 (OR 95% CI:0.535-0.834, P<0.001) times that of those with an income (Yuan) of less than 10 000. The results of the Poisson part are consistent with the results of the zero-inflated part in terms of age and education level. [Conclusion] Blood donor lapsing is overall related to factors such as gender, age, donation frequency, education, marital status and family income. It's essential to care for those blood donors prone to lapse to retain more regular blood donors.
6.Structure, content and data standardization of rehabilitation medical records
Yaru YANG ; Zhuoying QIU ; Di CHEN ; Zhongyan WANG ; Meng ZHANG ; Shiyong WU ; Yaoguang ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Jian YANG ; Na AN ; Yuanjun DONG ; Xiaojia XIN ; Xiangxia REN ; Ye LIU ; Yifan TIAN
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):21-32
ObjectiveTo elucidate the critical role of rehabilitation medical records (including electronic records) in rehabilitation medicine's clinical practice and management, comprehensively analyzed the structure, core content and data standards of rehabilitation medical records, to develop a standardized medical record data architecture and core dataset suitable for rehabilitation medicine and to explore the application of rehabilitation data in performance evaluation and payment. MethodsBased on the regulatory documents Basic Specifications for Medical Record Writing and Basic Specifications for Electronic Medical Records (Trial) issued by National Health Commission of China, and referencing the World Health Organization (WHO) Family of International Classifications (WHO-FICs) classifications, International Classification of Diseases (ICD-10/ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), this study constructed the data architecture, core content and data standards for rehabilitation medical records. Furthermore, it explored the application of rehabilitation record summary sheets (home page) data in rehabilitation medical statistics and payment methods, including Diagnosis-related Groups (DRG), Diagnosis-Intervention Packet (DIP) and Case Mix Index. ResultsThis study proposed a systematic standard framework for rehabilitation medical records, covering key components such as patient demographics, rehabilitation diagnosis, functional assessment, rehabilitation treatment prescriptions, progress evaluations and discharge summaries. The research analyzed the systematic application methods and data standards of ICD-10/ICD-11, ICF and ICHI Beta-3 in the fields of medical record terminology, coding and assessment. Constructing a standardized data structure and data standards for rehabilitation medical records can significantly improve the quality of data reporting based on the medical record summary sheet, thereby enhancing the quality control of rehabilitation services, effectively supporting the optimization of rehabilitation medical insurance payment mechanisms, and contributing to the establishment of rehabilitation medical performance evaluation and payment based on DRG and DIP. ConclusionStructured rehabilitation records and data standardization are crucial tools for quality control in rehabilitation. Systematically applying the three reference classifications of the WHO-FICs, and aligning with national medical record and electronic health record specifications, facilitate the development of a standardized rehabilitation record architecture and core dataset. Standardizing rehabilitation care pathways based on the ICF methodology, and developing ICF- and ICD-11-based rehabilitation assessment tools, auxiliary diagnostic and therapeutic systems, and supporting terminology and coding systems, can effectively enhance the quality of rehabilitation records and enable interoperability and sharing of rehabilitation data with other medical data, ultimately improving the quality and safety of rehabilitation services.
7.Role and Mechanism of Cucurbitacin B in Suppressing Proliferation of Breast Cancer 4T1 Cells via Inducing Ferroptosis
Yidan RUAN ; Huizhong ZHANG ; Huating HUANG ; Pingzhi ZHANG ; Aina YAO ; Yongqiang ZHANG ; Xiaohan XU ; Shiman LI ; Jian NI ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):91-97
ObjectiveTo explore the role of cucurbitacin B (CuB) in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB(0.2, 0.4, 0.8 μmol·L-1)on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium (MTT) assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay, and the levels of lactate dehydrogenase (LDH) in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species (ROS) levels in 4T1 cells were detected by flow cytometry, and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells, solute carrier family 7 member 11 (SCL7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), transferrin receptor protein 1 (TFR1), and ferritin heavy chain 1 (FTH1). ResultsCompared with that in the blank group, the survival rate of 4T1 cells in CuB groups was significantly decreased (P<0.05), and the number of cell clones in CuB groups was significantly reduced (P<0.01). In addition, compared with that in the blank group, the leakage of LDH in cells in CuB groups was significantly increased (P<0.01), and the mitochondrial membrane potential of cells in CuB groups decreased significantly (P<0.01). Cellular ROS levels were significantly elevated in CuB groups (P<0.01). The mitochondria of cells in CuB groups were obviously wrinkled, and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group, the protein expression of p53, ACSL4, and TFR1 were significantly up-regulated in CuB groups (P<0.05), and that of SLC7A11, GPX4, and FTH1 were significantly down-regulated (P<0.05). ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53, which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe3+ and down-regulates the expression of FTH1 to reduce the ability of iron storage, resulting in an elevated free Fe2+ level. It catalyzes the Fenton reaction, generates excess ROS, imbalances the antioxidant system and iron metabolism, and then induces ferroptosis in 4T1 cells.
8.Role and Mechanism of Cucurbitacin B in Suppressing Proliferation of Breast Cancer 4T1 Cells via Inducing Ferroptosis
Yidan RUAN ; Huizhong ZHANG ; Huating HUANG ; Pingzhi ZHANG ; Aina YAO ; Yongqiang ZHANG ; Xiaohan XU ; Shiman LI ; Jian NI ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):91-97
ObjectiveTo explore the role of cucurbitacin B (CuB) in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB(0.2, 0.4, 0.8 μmol·L-1)on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium (MTT) assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay, and the levels of lactate dehydrogenase (LDH) in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species (ROS) levels in 4T1 cells were detected by flow cytometry, and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells, solute carrier family 7 member 11 (SCL7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), transferrin receptor protein 1 (TFR1), and ferritin heavy chain 1 (FTH1). ResultsCompared with that in the blank group, the survival rate of 4T1 cells in CuB groups was significantly decreased (P<0.05), and the number of cell clones in CuB groups was significantly reduced (P<0.01). In addition, compared with that in the blank group, the leakage of LDH in cells in CuB groups was significantly increased (P<0.01), and the mitochondrial membrane potential of cells in CuB groups decreased significantly (P<0.01). Cellular ROS levels were significantly elevated in CuB groups (P<0.01). The mitochondria of cells in CuB groups were obviously wrinkled, and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group, the protein expression of p53, ACSL4, and TFR1 were significantly up-regulated in CuB groups (P<0.05), and that of SLC7A11, GPX4, and FTH1 were significantly down-regulated (P<0.05). ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53, which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe3+ and down-regulates the expression of FTH1 to reduce the ability of iron storage, resulting in an elevated free Fe2+ level. It catalyzes the Fenton reaction, generates excess ROS, imbalances the antioxidant system and iron metabolism, and then induces ferroptosis in 4T1 cells.
9.Therapeutic effect of anti-PD-L1&CXCR4 bispecific nanobody combined with gemcitabine in synergy with PBMC on pancreatic cancer treatment
Hai HU ; Shu-yi XU ; Yue-jiang ZHENG ; Jian-wei ZHU ; Ming-yuan WU
Acta Pharmaceutica Sinica 2025;60(2):388-396
Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8+ to CD4+ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8+ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).
10.Three new gallic acid sugaresters from Elaeagnus oxycarpa Schlechtend leaves and their antioxidant and tyrosinase inhibitory activities
Feng-zhen CUI ; Jian-hong FU ; Guo-yan XU ; AYEKABAYR·EKBAYR ; Chang-da MA
Acta Pharmaceutica Sinica 2025;60(2):434-441
Five compounds were isolated and purified from the water extract of

Result Analysis
Print
Save
E-mail