Objective: To investigate the ameliorative effect of kidney bean enzyme crude extract (KBECE) on non-alcoholic fatty liver disease (NAFLD) in mice. Methods: Total of 30 female ICR mice were randomly divided into 10 mice fed with normal diet (normal group), and the other 20 mice were fed with 45% high fat diet to establish the model of NAFLD. After 2 weeks, they were randomly divided into high fat diet control group (high fat group) and KBECE intervention group (intervention group), with 10 mice in each group. The mice were treated with PBS and KBECE daily for 6 weeks, and the body weight was recorded every week. At the 8th week, the mice were sacrificed and the blood and liver tissue were collected. The pathological changes of liver of NAFLD mice were observed by HE and Masson staining. The contents of MDA in liver tissue, TG, TC and LDL-C in serum were measured by commercial kits. Results: KBECE decreased the relative growth rate of body weight of mice, KBECE could improve hepatic steatoid degeneration and fibrosis in hyperlipidemic mice. Compared with the high fat group, the liver index of the intervention group decreased respectively (P<0.05), the content of MDA in liver tissue and the content of TG, TC, LDL-C in serum decreased respectively (all P<0.05). Conclusion: KBECE can improve the NAFLD induced by high fat diet by repairing the disorder of lipid metabolism and inhibiting oxidative stress.

江苏大学学报（医学版）2025年第1期目次

Objective: To explore the effect of Bupleurum extract on non-alcoholic fatty liver disease (NAFLD) and its relationship with amine oxidase copper-containing 3 (AOC3)-phosphatidylinositol 3-KINASE (PI3K)/protein kinase B (AKT) signaling pathway. Methods: A total of 69 patients with NAFLD in Zhenjiang Hospital of Chinese Traditional and Western Medicine from May 2022 to May 2023, and another 70 healthy controls were enrolled in the study. The contents of phenylalanine (Phe) and tyrosine (Tyr) in serum were measured by ELISA. The relative expressions of AOC3 mRNA and protein in serum were detected by qRT-PCR and Western blotting, respectively. The NAFLD model of C57BL/6 mice was constructed. After modeling, they were divided into control group, model group, and low-dose group (50 mg/kg), medium-dose group (75 mg/kg), and high-dose group (100 mg/kg) of Bupleurum extract, with 6 mice in each group. The Bupleurum extract group was given the corresponding Bupleurum extract, the control group and the model group were given corresponding volumes of normal saline by gavage every day, respectively. Four weeks later, the contents of total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-α) in serum were detected by ELISA. Additionally, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in liver tissues were measured. Hepatic pathology was evaluated by hematoxylin-eosin (HE) staining. The siRNA2 (50 nmol/L) was screened out by knocking down the expression of AOC3 by siRNA transfection. Hepatocytes were divided into control group, model group, siRNA2 group (50 nmol/L), Bupleurum group (100 μg/mL), and combined group (50 nmol/L siRNA2 + Bupleurum 100 μg/mL). The cell proliferation rate, apoptosis rate and the protein expressions of p-PI3K and p-AKT were detected by MTT, flow cytometry and Western blotting, respectively. Results: The contents of Phe and Tyr in the serum of patients with NAFLD and model mice, as well as the relative expression levels of AOC3 mRNA and protein, were significantly higher than those of healthy individuals and the control group, respectively (P<0.01). Compared with the model group, the levels of Phe, Tyr, TC, TG, LDL-C, NO and TNF-α in the serum of mice in the medium and highdose Bupleurum groups were significantly decreased (P<0.05 or P<0.01), the level of HDL-C was significantly increased (P<0.01), and liver fibrosis and reactive oxygen species accumulation were significantly attenuated (P<0.01). Compared with the siRNA2 group and the Chaihu group, the proliferation rate of hepatocytes in the combined group was significantly increased (P<0.01), the apoptosis rate was greatly decreased (P<0.01), the contents of lipotoxic metabolites (TG, TC) were significantly decreased (P<0.01), and oxidative stress was significantly inhibited (decreased content of MDA, increased SOD/GSH-Px, P<0.01 or P<0.05), liver function was significantly improved (decreased contents of ALT and AST, P<0.01), and the PI3K/AKT signaling pathway was activated (the expressions of AOC3, p-PI3K, and p-AKT decreased, P<0.01). Conclusion: Bupleurum extract may attenuate NAFLD by regulating the metabolism of amino acids related to NAFLD, reducing the content of peroxides, blocking the excessive activation of the PI3K/AKT pathway mediated by AOC3, reducing the expression of AOC3 and phosphorylating the expression of PI3K/AKT.

Objective: Investigating the inhibitory effects of sodium butyrate (NaB) on oleic acid (OA) and advanced glycation end-products (AGEs), and exploring its impact and mechanism on lipid deposition and inflammatory response in HepG2 cells. Methods: HepG2 cells were divided into 5 groups: control group (NC), cells without any treatment; OA group, cells treated with 0.05 mmol/L OA for 2 h; OA+AGEs group, cells co-treated with 0.05 mmol/L OA and 200 μg/mL AGEs for 2 h; OA+AGEs+low concentration NaB group (NaB-L), OA+AGEs+high concentration NaB group (NaB-H), where NaB-L group and NaB-H group cells were pre-treated with concentrations of 100 μmol/L and 400 μmol/L NaB for 24 h, then treated with 0.05 mmol/L OA and 200 μg/mL AGEs for 2 h. qRT-PCR was used to detect the mRNA expressions of inflammatory factors, mitochondrial autophagy-related genes, and cholesterol metabolism-related genes. Western blotting was used to detect the expressions of LC3-Ⅱ and P62, as well as the distribution of cytochrome C (CytoC) in mitochondria and cytoplasm; flow cytometry was used to detect cellular reactive oxygen species (ROS) and mitochondrial membrane potential levels. Results: Compared to the NC group, lipid deposition in the cells, the NLRP3, Caspase-1, IL-1β, HMGR mRNA, P62, cytoplasmic CytoC expression levels, and ROS levels in the OA+AGEs group were significantly increased (P<0.05), while the LDLR, PINK1, Parkin mRNA expression levels and mitochondrial membrane potential was significantly decreased (P<0.05), as well as the expression levels of CytoC in mitochondria, and LC3-Ⅱ (P<0.05). Compared to the OA+AGEs group, both low and high concentrations of NaB significantly reduced lipid deposition in the cells, the expressions of NLRP3, Caspase-1, IL-1β, HMGR mRNA, P62, cytoplasmic CytoC and ROS levels  (P<0.05), while significantly increased the expression of LDLR, PINK1, Parkin mRNA and mitochondrial membrane potential (P<0.05), as well as the expressions of CytoC in mitochondria, LC3-Ⅱ(P<0.05). Conclusion: NaB enhances mitophagy via the PINK1/Parkin pathway, reducing ROS accumulation and CytoC release, thereby suppressing OA/AGEs-induced lipid deposition and inflammatory response.

非酒精性脂肪性肝病(non-alcoholic fatty liver disease，NAFLD)是目前我国最常见的慢性肝病，前期无明显临床症状，多于体检时发现肝功能化学指标的改变。随着病情进展，NAFLD会出现不可逆性的肝损伤，如不加以规范治疗，后期易导致肝纤维化和肝癌。棕榈油酸是一种广泛存在于自然界的单不饱和脂肪酸。近来研究发现，棕榈油酸是体内固有的脂质调节因子，具有包括改善胰岛素抵抗、维持脂质稳态以及减少组织炎症等功能，其在防治NAFLD方面具有独特的自身优势。因此，本文对棕榈油酸防治NAFLD的四大途径进行归纳并予以综述。

目的： 分析脑损伤早产儿脑血流动力学变化及早产儿脑损伤的相关影响因素。方法： 选择2018年6月至2022年12月在江苏大学附属医院分娩的胎龄小于37周的单胎早产儿80例，其中脑损伤组27例，无脑损伤组53例。对比两组早产儿的脑血流动力学变化情况，分析早产儿脑损伤的危险因素。结果： 脑损伤组的动脉血流助力指数（RI）和动脉血流搏动指数（PI）高于无脑损伤组，而动脉舒张期血流速度（Vd）、动脉收缩期血流速度峰值（Vs）、动脉血流平均速度（Vm）则明显低于无脑损伤组（P均<0.05）。差异性分析结果表明，与无脑损伤组比较，早产儿脑损伤组胎龄、出生时体重、机械通气、高危因素、1 min及5 min Apgar评分、酸中毒及血糖水平差异有统计学意义（P<0.05）；多因素Logistic回归分析结果表明，上述指标均为早产儿脑损伤的影响因素。结论： 脑血流动力学相关指标为临床诊断早产儿脑损伤提供一定的依据，关注相关影响因素可及时预防和减少脑损伤发生率。

目的： 探讨经阴道分娩前纤维蛋白原(fibrinogen,Fib)和中性粒细胞delta指数(delta neutrophil index，DNI)与产后出血患者输血需求的关系及临床意义。方法： 连续纳入2019年1月至2023年12月于无锡市妇幼保健院产科经阴道分娩24 h内发生产后出血患者206例，根据是否需要输血分为输血组和非输血组，收集临床资料，包括分娩前24 h内Fib和DNI，行回顾性分析。利用二元Logistic回归分析预测产后输血的独立危险因素，并绘制受试者工作特征(ROC)曲线以计算DNI和Fib预测产后输血需求的曲线下面积(AUC)，采用约登指数法计算最佳截断值。结果： 与非输血组相比，输血组Fib和收缩压、血红蛋白等水平明显降低(P＜0.01)，DNI等明显升高(P＜0.01)。二元Logistic回归显示，Fib(OR：0.215，95%CI：0.102～0.452，P＜0.001)和DNI(OR：1.247，95%CI：1.023～1.520，P＜0.001)是输血需求的独立预测因子。ROC曲线结果显示，Fib和DNI预测输血需求的AUC分别为0.748(95%CI：0.683～0.806，P＜0.001)和0.772(95%CI：0.697～0.829，P＜0.001)，最佳截断值分别为2.56 g/L和3.6%，Fib+DNI联合预测输血需求AUC值为0.941(95%CI：0.900～0.969，P＜0.001)。结论： Fib与DNI联合检测可提高对经阴道分娩产后出血患者输血需求的预测能力。

Objective: To investigate the effect of 3,3′-diindolylmethane (DIM) on paclitaxelresistant nonsmall cell lung cancer A549/T cells and explore its underlying mechanism. Methods: Western blotting was used to detect transferrin receptor (TFRC), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in human normal bronchial epithelial BEAS-2b cells, human NSCLC A549 cells, paclitaxel-resistant human NSCLC A549/T cells, and human large cell lung cancer H460 cells to select the optimal cell line. A549 and A549/T cells were treated with various concentrations of DIM (0, 20, 40, 80, 160 μmol/L), and cell proliferation was assessed by CCK-8 assay; and the expression of TFRC, SLC7A11 and GPX4 proteins in A549/T cells were determined by Western blotting to screen out the optimal DIM concentration. Additionally, A549/T cells were divided into the control group, which was cultured in highglucose medium containing 10% fetal bovine serum for 24 h; the Erastin group, treated with 10 μmol/L Erastin for 12 h alone; the DIM group, treated only with 80 μmol/L DIM for 24 h; the DIM+Erastin group, cells were pre-treated with 10 μmol/L Erastin for 12 h, then treated with 80 μmol/L DIM in the following 24 h. Cell viability was detected by CCK8 assay, and the expression of TFRC, SLC7A11 and GPX4 proteins was assessed by Western blotting. Results: Compared with the BEAS-2b group, TFRC and SLC7A11 expression was significantly increased in A549 cells (P<0.05), TFRC, SLC7A11 and GPX4 expression was significantly increased in A549/T cells (P<0.05). No significant differences in TFRC, SLC7A11 and GPX4 expression were observed in H460 cells (P>005). In A549/T cells, compared with the 0 μmol/L group, the expression of TFRC, SLC7A11 and GPX4 proteins showed significant alterations in the 80 μmol/L DIM group (all P<0.05). Compared with 0 μmol/L DIM group, in A549 cells, cell viability was significantly decreased in 20, 40, 80 and 160 μmol/L DIM groups (all P<0.05); in A549/T cells, cell proliferation was significantly decreased in 80 and 160 μmol/L DIM groups (all P<0.05). In A549/T cells, compared with the control group, DIM group, Erastin group and DIM+Erastin group showed a significant increase in TFRC expression (all P<0.05), while the expression of SLC7A11 and GPX4 proteins significantly decreased (all P<0.05), and cell proliferation significantly decreased (all P<0.05). Conclusion: DIM may inhibit the proliferation of paclitaxel-resistant non-small cell lung cancer A549/T cells by inducing ferroptosis, and ferroptosis inducers could be used to enhance the anti-cancer effect of DIM.

Objective: To develop and validate a nomogram model utilizing CT radiomics features for predicting the efficacy of radiotherapy in esophageal squamous cancer. Methods: A retrospective analysis was conducted for 201 patients diagnosed with esophageal squamous cancer at Xuzhou Cancer Hospital and Xuzhou Mining Group General Hospital between January 2019 and January 2024. The dataset was partitioned into the training set (n=79), the testing set (n=34), and the external validation set (n=88). Radiomics features were extracted from pre-radiotherapy CT images of patients, followed by dimensionality reduction. Univariate and multivariate Logistic regression analyses were employed to identify the significant clinical features of the constructed model. The support vector machine learning algorithm was utilized to construct three predictive models: the clinical model, the radiomics model, and the nomogram model. The nomogram model was visualized using a nomogram. The predictive performance of the constructed model was assessed through external validation. The model′s clinical applicability were measured by dicision curve analysis (DCA). Results: A total of 1 834 CT radiomics features were extracted. Following feature screening and dimensionality reduction, eleven optimal radiomics features were selected for subsequent model construction. The area under curve (AUC) for the nomogram model in the training set was 0980, which exceeded that of both the clinical model (AUC=0.859) and the radiomics model (AUC=0.926). In the testing set, the AUC for the nomogram model was 0.834, surpassing the clinical model (AUC=0.638) and the radiomics model (AUC=0.818). Furthermore, in the external validation set, the AUC for the nomogram model was 0883, outperforming the clinical model (AUC=0.652) and the radiomics model (AUC=0.765). DCA results demonstrated that the nomogram model had the highest clinical net benefit in comparison to the alternative models. Conclusion: The developed nomogram model, which integrates CT radiomics and clinical features, may be applied for predicting the efficacy of radiotherapy for esophageal squamous cancer.

Objective: To investigate the impact of lipotoxic hepatocytederived exosome (LTH-ex) on ferroptosis and activation of hepatic stellate cell (HSC). Methods: Lipotoxic damage was induced in the human liver cell line LO2 using oleic acid and palmitic acid. The supernatants of the lipotoxic damaged liver cells were collected and LTH-ex was extracted through ultracentrifugation. The characterization of LTH-ex was identified using transmission electron microscopy and Nanosight nanoparticle analysis system, including assessing morphology, particle size and concentration, and LTH-ex surface markers through Western blotting. The human HSC cell line LX-2 was cocultured with LTH-ex or the ferroptosis activator Erastin for 48 h, and then all cells were divided into three groups: the PBS control group, the LTH-ex treatment group, and the co-treatment group consisting of LTH-ex and the ferroptosis inducer Erastin. Cell viability and mitochondrial membrane potential of LX-2 were evaluated using FDA and JC-1 staining. The iron ion concentration kit was used to detect the iron level in LX-2, the expression of mRNA and protein of death suppressor genes GPX4, xCT, and HSC activation gene α-SMA, were measured through qRT-PCR and Western blotting. Additionally, a mouse model of nonalcoholic fatty liver disease was established by feeding a high-fat diet, followed by injection of LTH-ex through the tail vein. Liver tissue structure was observed using HE staining, while GPX4 and α-SMA protein expression was assessed through immunohistochemistry staining. Sirius red staining was employed to detect collagen deposition in the liver tissue. Results: The LTH-ex particles were approximately 110 nm in size, displaying the typical lipid bilayer structure of exosomes and containing exosome marker proteins TSG101, Alix, and CD63. In comparison to the PBS control group, the LTH-ex treatment group demonstrated enhanced viability of LX-2 cells, an increased mitochondrial membrane potential, decreased iron levels, and upregulation of the ferroptosis-inhibiting genes GPX4 and xCT, as well as HSC activation gene α-SMA. Conversely, when compared to the LTH-ex treatment group, the co-treatment group of LTH-ex and the ferroptosis inducer Erastin exhibited reduced LX-2 cell viability and mitochondrial membrane potential, alongside downregulation of GPX4, xCT, and α-SMA. HE staining, immunohistochemistry, and Sirius red staining demonstrated that LTH-ex could exacerbate vacuolar degeneration of hepatocytes in the liver tissue of mice with nonalcoholic fatty liver disease. Additionally, LTH-ex promoted the expression of GPX4 and αSMA proteins and increased collagen deposition in the liver tissue. expression. Conclusion: LTH-ex increase the cell viability of hepatic stellate cells and the expression of ferroptosis inhibitory genes GPX4 and xCT, and it may be implicated that LTH-ex may promote hepatic stellate cell activation by inhibiting ferroptosis, and exacerbate collagen deposition in the liver tissue of non-alcoholic fatty liver disease mice.