Oxidative stress represents a pivotal mechanism in the pathogenesis of numerous chronic diseases. The Kelch-like ECH-associated protein 1-transcription factor NF-E2 p45-related factor 2 (KEAP1-NRF2) pathway plays a crucial role in maintaining redox homeostasis and regulating a multitude of biological processes such as inflammation, protein homeostasis, and metabolic homeostasis. In this paper, we present the findings of recent studies on the KEAP1-NRF2 pathway, which have revealed that it is aberrantly regulated and induces oxidative stress injury in a variety of diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, respiratory diseases, digestive diseases, and cancer. Given this evidence, targeting KEAP1-NRF2 represents a highly promising avenue for developing therapeutic strategies for chronic diseases, and thus the development of appropriate therapeutic strategies based on the targeting of the NRF2 pathway has emerged as a significant area of research interest. This paper highlights an overview of current strategies to modulate KEAP1-NRF2, as well as recent advances in the use of natural compounds and traditional Chinese medicine, with a view to providing meaningful guidelines for drug discovery and development targeting KEAP1-NRF2. Additionally, it discusses the challenges associated with harnessing NRF2 as a therapeutic target.

Objective: To systematically evaluate the efficacy of mesenchymal stem cells (MSCs) for acute kidney injury (AKI) in preclinical studies and to explore the optimal transplantation strategy of MSCs by network meta-analysis with the aim of improving the efficacy of stem cell therapy.Methods: Computer searches of PubMed, Web of Science, Cochrane, Embase, CNKI, Wanfang, VIP, and CBM databases were conducted until 17 August 2022. Literature screening, data extraction and quality evaluation were performed independently by two researchers.Results and Discussion: A total of 50 randomized controlled animal studies were included. The results of traditional meta-analysis showed that MSCs could significantly improve the renal function and injured renal tissue of AKI rats in different subgroups. The results of network meta-analysis showed that although there was no significant difference in the therapeutic effect between different transplant routes and doses of MSCs, the results of surface under the cumulative ranking probability curve (SUCRA) showed that the therapeutic effect of intravenous transplantation of MSCs was better than that of arterial and intrarenal transplantation, and the therapeutic effect of high dose (>1×106) was better than that of low dose (≤1×106). However, the current preclinical studies have limitations in experimental design, measurement and reporting of results, and more high-quality studies, especially direct comparative evidence, are needed in the future to further confirm the best transplantation strategy of MSCs in AKI.Systematic Review Registration: identifier https://CRD42022361199, https://www.crd.york.ac.uk/prospero.

目的:观察以温补脾肾法为指导的理中汤合四神丸对脾肾阳虚型溃疡性结肠炎(UC)大鼠模型病变结肠组织中JAK2、STAT3、p-STAT3、SOCS6蛋白及基因表达的影响.方法:采用病证结合造模方法复制脾肾阳虚型UC模型,成模大鼠随机分为模型组、柳氮磺砒啶组(SASP组)、理中汤合四神丸高、中、低剂量组,16只/组,同时设16只大鼠作为空白组.空白组与模型组给予蒸馏水灌胃,各治疗组给予对应的药物及剂量灌胃治疗,连续21 d.HE染色观察大鼠结肠黏膜组织病理变化;免疫组化法检测大鼠结肠黏膜组织中JAK2、STAT3、p-STAT3、SOCS6蛋白表达情况;RT-qPCR检测大鼠JAK2、STAT3、SOCS6 mRNA表达情况;ELISA检测大鼠组织和血清中TGF-β1、ICAM-1含量.结果:与空白组相比,模型组大鼠结肠黏膜组织JAK2、STAT3、p-STAT3蛋白表达显著升高(P<0.01),JAK2、STAT3、p-STAT3蛋白着色深,表达呈强阳性,SOCS6蛋白表达显著降低(P<0.01),SOCS6蛋白着色浅,表达呈弱阳性.JAK2、STAT3 mRNA表达显著升高,SOCS6 mRNA表达显著降低(P<0.01),组织和血清中TGF-β1含量显著降低(P<0.01),ICAM-1含量显著升高(P<0.01);与模型组相比,中药高、中剂量组及SASP组JAK2、STAT3、p-STAT3蛋白表达显著降低(P<0.01),JAK2、STAT3、p-STAT3蛋白着色浅,表达呈弱阳性,SOCS6蛋白表达显著升高(P<0.01),SOCS6蛋白着色深,表达呈强阳性.JAK2、STAT3 mRNA表达显著降低(P<0.01),SOCS6 mRNA表达显著升高(P<0.01),组织和血清中TGF-β1含量显著升高(P<0.01),ICAM-1含量显著降低(P<0.01).结论:以温补脾肾法为指导的理中汤合四神丸可能通过抑制JAK2/STAT3-SOCS6信号通路的激活,调节免疫系统平衡,修复受损结肠黏膜,达到治疗UC的目的.

未分化高级别多形性肉瘤是一种老年人多见的恶性软组织肿瘤,好发于四肢和腹膜后,通常表现为不断增大的无痛性肿块.本文报道的1例66岁肺原发未分化高级别多形性肉瘤患者,以期为临床诊断提供思路,提高对该病的认识.

低度恶性肌纤维母细胞肉瘤(low-grade myofibroblastic sarcoma,LGMS)是一种由肌纤维母细胞组成或者起源于肌纤维母细胞的间叶组织肿瘤.在局部麻醉下,对1例原发于乳腺上的LGMS的患者行右侧乳腺肿物切除术,术后病理组织学形态表现为瘤组织由梭形细胞构成,呈漩涡状或束状排列,背景基质黏液样,核分裂象易见;免疫组织化学:波形蛋白、平滑肌肌动蛋白、CD34(+);对LGMS的临床病理特征、影像学特征、诊断与鉴别要点进行分析,以提高临床医师的认识.

Abstract Background Formaldehyde (FA) has been classified as a human carcinogen by the International Agency for Research on Cancer (IARC) and has toxic effects on various tissues and cells. It is reported that FA can accelerate cellular senescence in mice HT22 cells and induce the apoptosis of BALB/c mice BMSCs. Our previous study has confirmed that FA has genotoxic effects on BMSCs by the formation of DNA-protein crosslinks (DPC), sister chromatid exchange (SCE) and micronucleus (MN). However, whether FA causes apoptosis and senescence effects on human BMSCs has not been fully investigated. The aim of this study is to explore the toxic effects and mechanisms of FA on BMSCs based on senescence and apoptosis. Method In this study, Human BMSCs were cultured in vitro and randomly divided into a blank group, a control group and five groups of cells treated with different concentrations (60, 90, 120, 150 and 180 umol/L) of FA. And the cell groups were cultured for 6, 12 and 24 hours. The effect of different concentrations of FA on the viability of human BMSCs was investigated using the MTT assay. Based on the results of MTT assay, we selected the cell group with 120 µmol/L FA for 24 hours for the following experiments. Changes of FA on the morphology of BMSCs were analyzed using the phase-contrast microscope and phalloidin/hoechst33258 staining. We performed bioinformatic analysis on the RNA-Seq data, including differential expression analysis, GO and KEGG analysis in order to further understand the mechanisms of toxicity of FA on BMSCs. The changes in the mRNA and protein expression levels of PIK3CA, Caspase3, Bcl2, P53 and P21 of BMSCs following exposure to FA were detected using qRT-PCR and western blotting. Result When FA concentration reached 90 umol/L, the inhibition of proliferation activity of human BMSCs began to appear, and increased with the increase of FA concentration and time. By morphological detection, we observed that BMSCs treated with 120 µmol/L FA became smaller and rounder, of which the cytoskeleton was disordered and the nuclei were pyknotic, dense stained and fragmented, even with apoptotic bodies formed. The results of the bioinformatics analysis showed that 249 differentially expressed mRNAs (DE mRNAs) were identified in the RNA-seq samples, which included 158 upregulated and 91 downregulated mRNAs. And functional enrichment analysis revealed the pathway of accumulation to cellular senescence and apoptosis. Further assays were performed on factors of the PI3K/P53 pathway, which was a pathway related to senescence and apoptosis. The mRNA and protein expression levels of Caspase3, P53 and P21 in the 120 µmol/L FA-treated group were significantly higher than those in the control group, while the mRNA expression levels of PIK3CA and Bcl2 were significantly lower than those in the control group. Treatment with 120 µmol/L FA reduced the protein expression levels of PIK3CA. Conclusion FA had toxic effects on human BMSCs and the mechanism might be related to the regulation of PI3K/P53 signaling pathway to promote cellular senescence and apoptosis.

分析1例腮腺转移性视网膜母细胞瘤的临床病理学特征并复习相关文献。患儿为女性，9岁，因左侧腮腺增大，肿胀不适入院。既往有视网膜母细胞瘤病史6年。大体送检腮腺穿刺灰白色线状组织2条，长1.8cm-2cm。组织学肿瘤由细胞核深染的小圆细胞组成，胞质少，核浆比高，排列紧密，弥漫分布，可见不同分化的菊形团结构。免疫组织化学显示瘤细胞表达神经标志NSE、Syn、CD56，不表达CgA、GFAP、CKp、S100、Melan-A、HMB45、LCA、CD99，Ki67 index≈90%。腮腺转移性视网膜母细胞瘤极其罕见，明确诊断依靠病理活检和免疫组化，并结合临床病史。

肉瘤是起源于间叶组织的异质性恶性肿瘤,仅占成人恶性肿瘤的 1％. 未分化高级别多形性肉瘤(Undifferentiated high-grade pleomorphic sarcoma,UHGPS)过去被称为多形性恶性纤维组织细胞瘤(Pleomorphic malignant fibrous histiocy-toma,PMFH),常发生于四肢和腹膜后. 目前,UHGPS 的发病机制尚不完全清楚.

Background: Yolk sac tumor is a germ cell tumor (GCT) that occurs in infants and adolescents and affects various sites. There is a trend to treat pediatric renal tumors before a tissue diagnosis. We report a renal yolk sac tumor clinically misdiagnosed as Wilms tumor, based on ultrasound (US) and MRI.Case Report: This 21-month-old male infant was discovered to have a space occupying lesion in the right kidney. Because the tumor was large, initial radiotherapy preceded surgical resection. Histologically, the tumor was a yolk sac tumor.Conclusion: Imaging examination of renal yolk sac tumor can easily be misdiagnosed as Wilms tumor. SIOP treatment plan for Wilms tumor requires preoperative chemotherapy, which is different from the treatment regimen for yolk sac tumor. Preoperative alpha-fetoprotein could have been helpful in avoiding this clinical misdiagnosis.

Abstract Background Gastric cancer is a malignant tumor with a high incidence and mortality rate. Angiogenesis is necessary for tumor infiltration and metastasis, and also affects patient prognosis. YKL-39 has monocyte chemotactic activity and pro-angiogenic activity in some of the tumors. In this study, we will investigate the relationship between YKL-39 and tumor-associated macrophages and microangiogenesis in gastric cancer and explore the value of YKL-39 as a prognostic biomarker for gastric cancer. Methods A total of 119 patients with gastric cancer who had undergone gastrectomy at the 940th Hospital of the Joint Security Force between 2013 and 2019 were included in this study, and the protein expression of YKL-39, CD68, and CD34 was detected by immunohistochemistry, and intracellular expression of YKL-39 and CD68 was detected by immunofluorescence. Results Our results showed that YKL-39 was expressed in both nucleus and cytoplasm of gastric cancer tissues and tumor mesenchyme, and the expression of YKL-39 was positively correlated with CD68 and CD34, as well as the high expression of YKL-39 was associated with poor prognosis of gastric cancer patients. Conclusion In gastric cancer, YKL-39 expression positively correlated with the degree of tumor-associated macrophage infiltration and angiogenesis, and it could be a potential prognostic marker and therapeutic target for gastric cancer.

目的 探讨舒肝和络醒脾方(SHXD)的抗肝纤维化(HF)作用.方法 将60只SPF级Wistar大鼠随机分为空白组、模型组、对照组和低、中、高剂量实验组,每组10只;除空白组外,其余组大鼠均腹腔注射40％四氯化碳构建HF大鼠模型.模型组灌胃给予与实验组等量的0.9％NaCl;对照组灌胃给予0.50 mg·kg-1秋水仙碱溶液;低、中、高剂量实验组分别灌胃给予3.15,6.30和12.60 g·kg-1(生药/体质量)SHXD.5组大鼠每天给药1次,连续8周.空白组不做任何处理,正常喂食喂水,作为对照观察使用.用实时荧光定量聚合酶链反应检测肝组织中转化生长因子β1(TGF-β1)和果蝇母本抗生存因子蛋白(Smad2)mRNA的表达水平,用酶联免疫吸附实验法检测血清中HF 4项含量.结果 中、高剂量实验组和对照组、模型组、空白组的TGF-β1 mRNA表达水平分别为1.36±0.19,1.40±0.12,1.53±0.14,1.58±0.13和1.00±0.00,Smad2 mRNA表达水平分别为1.17±0.06,1.24±0.09,1.52±0.14,1.42±0.13和1.00±0.00,层黏连蛋白的含量分别为(353.92±27.40),(309.46±22.57),(341.48±25.14),(436.71±39.51)和(205.89±27.00)ng·mL-1,透明质酸酶的含量分别为(117.50±9.80),(95.48±8.83),(123.24±11.02),(143.01±13.20)和(79.62±6.79)ng·mL-1,Ⅳ型胶原的含量分别为(60.93±6.02),(51.57±5.12),(68.91±7.35),(82.91±8.61)和(41.93±5.04)ng·mL-1,Ⅲ型前胶原分别为(1.85±0.33),(2.04±0.24),(2.11±0.30),(3.38±0.38)和(1.83±0.26)ng·mL-1.中、高剂量实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.05).结论 SHXD具有一定的抗HF作用,以高、中剂量作用效果最为显著;TGF-β/Smad通路可能为其抗HF的信号途径之一.

目的 基于网络药理学探究敦煌平胃丸对人胃癌细胞株SGC-7901的抑制作用.方法 建立BALB/c裸鼠移植瘤模型,随机分为对照组、顺铂组、敦煌平胃丸组,每组8只,分别给予生理盐水腹腔注射、顺铂腹腔注射、敦煌平胃丸灌胃给药10 d,通过抑瘤率、瘤体形态、肿瘤细胞凋亡检测抑瘤情况.通过TCMSP、NCBI、TTD等在线数据库构建"药物-成分-靶点"网络,得到敦煌平胃丸治疗胃癌的有效成分及关键靶点,分析关键靶点的KEGG通路和GO功能.结果 与对照组比较,顺铂组、敦煌平胃丸组小鼠移植瘤体积均减小(P<0.01),肿瘤细胞凋亡率增高(P<0.01),细胞和组织异型性降低.网络药理学分析得到胃癌靶点720个,敦煌平胃丸有效成分133个,成分靶点670个,以3种互作分析方法得到敦煌平胃丸治疗胃癌的关键靶点103个,关键靶点对应的关键成分84个,KEGG通路富集得到16536条信号通路,TOP20的通路与癌症密切相关.结论 敦煌平胃丸对胃癌移植瘤具有抑制作用,网络药理学显示该复方中多种小分子通过多个关键靶点和对应的多条通路,以"多点显效,协同增效"的特点发挥抑瘤作用.

Background. Gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer-related deaths. Because GC has the characteristics of high heterogeneity, unclear mechanism, limited treatment methods, and low five-year survival rate, it is necessary to find the prognostic biomarkers of GC and explore the mechanism of GC. Methods. We first identified differentially expressed genes (DEGs) between gastric cancer and normal gastric cells through expression analysis. A protein-protein interaction (PPI) network was constructed to find tightly connected modules. We performed survival analysis on the DEGs in the modules to identify genes with prognostic significance. Gene set enrichment analysis (GSEA) was used to identify gene enrichment pathways. Finally, we used our own collected clinical samples of 119 gastric adenocarcinoma (STAD) tissues and 40 normal gastric tissues to perform immunohistochemical (IHC) staining to verify the differential expression of COL8A1 in STAD tissues and normal gastric tissues and its correlation with epithelial-mesenchymal transition- (EMT-) related factors. Results. We identified 356 DEGs through differential expression analysis. Through PPI analysis and survival analysis, we determined that the collagen type VII alpha-1 chain (COL8A1) gene has prognostic significance. GSEA analysis showed that COL8A1 was significantly enriched in the EMT. IHC results showed that COL8A1 was upregulated in STAD tissues and could be used as an independent prognostic factor and was related to EMT. Conclusion. This study shows that COL8A1 is related to the prognosis of GC patients and might affect the progress of GC through the EMT pathway. Therefore, COL8A1 may be a biomarker for predicting the prognosis of GC.

目的 探讨半乳糖凝集素-3(Gal-3)、细胞角蛋白19(CK19)、间质瘤相关抗体-1(HBME-1)、细胞周期蛋白D1(cyclin D1)、p53在甲状腺乳头状癌(PTC)中的诊断价值.方法 收集2016年11月-2019年3月甘肃省人民医院PTC(T-PTC组)及配对正常甲状腺组织(N-PTC组)各125例,采用免疫组织化学EnVision二步法检测2组中Gal-3、CK19、HBME-1、cyclin D1、p53的表达水平,比较其表达率、灵敏度、特异度、准确度等.结果 T-PTC组的Gal-3、CK19、HBME-1、cyclin D1、p53阳性表达率明显高于N-PTC组的(P＜0.05).各标志物单独用于PTC诊断时,cyclin D1的灵敏度(99.20％)和准确度(97.60％)最高,HBME-1、p53的特异度(100.00％)最高;多种标志物联合应用时,CK19+cyclinD1联合检测的灵敏度(98.40％)、特异度(99.20％)和准确度(98.80％)综合比较最优,最适合用于PTC的诊断.结论 Gal-3、CK19、HBME-1、cyclin D1、p53是PTC的重要标志物,CK19+cyclin D1联合检测可用于辅助PTC诊断.

Background. Gastric adenocarcinoma (GAD) is one of the most common tumors in the world and the prognosis is still very poor. Objective. We sought to identify reliable prognostic biomarkers for the progression of GAD and the sensitivity to drug therapy. Method. The RNA sequencing data of GAD was downloaded from the Cancer Genome Atlas (TCGA) database and used for analysis. Differentially expressed, immune-related lncRNA (DEIRlncRNA) was characterized by differential analysis and correlation analysis. Univariate Cox regression analysis was used to identify DEIRlncRNA associated with prognosis. Least absolute shrinkage and selection operator (LASSO) regression analysis allowed us to determine a signature composed of eight IRlncRNAs. Based on this signature, we further performed gene set enrichment analysis (GSEA) and somatic mutation analysis to evaluate the ability of this signature to predict prognosis. Results. In total, 72 immune-related lncRNAs (DEIRlncRNAs) with prognostic value were identified. These lncRNAs were used to construct a model containing eight immune-related lncRNAs (8-IRlncRNAs). Based on this risk model, we divided GAD patients into high-risk and low-risk groups. The analysis showed that the prognosis of the two groups was different and that the high-risk group had worse overall survival (OS). Immune cell infiltration analysis showed that the proportion of memory B cells increased in the high-risk group while the proportion of macrophages M1, T cells, CD4 memory-activated cells, and T cell follicular helpers decreased. GSEA results showed that 8-IRlncRNA was significantly enriched in tumorigenesis pathways such as myc. The results of somatic mutation analysis showed that the CDH1 gene was significantly mutated in the high-risk group. Conclusion. A prognostic signature of 8-IRlncRNAs in GAD was established and this signature was able to predict the prognosis of GAD patients.

患者,女,67岁,因"发现双侧颈部包块20余年,增大伴疼痛半年余"入院.患者20年前查体时发现体双侧甲状腺包块,包块较小,未给予重视,未行相关诊疗.半年前自觉双侧甲状腺包块明显增大,偶伴有疼痛.查体:颈软,无抵抗,未见颈静脉怒张,颈动脉搏动正常,未闻及明显血管杂音,气管右偏,左侧可触及肿大包块,范围约8.0 cm×5.0 cm,表面光滑,局部皮肤无红肿及破溃,轻微压痛,与周围组织无明显粘连,随吞咽动作上下移动,未触及明显震颤.临床诊断:甲状腺占位性病变.于全麻下行左侧甲状腺全切术、颈部淋巴结清扫术.

Gastric cancer has a high incidence and mortality rate. Angiogenesis is necessary for tumor infiltration and metastasis and affects patient prognosis. YKL-39 has monocyte chemotactic activity and pro-angiogenic activity in some tumors. In this study, we investigated the relationship between YKL-39 and tumor-associated macrophages and microangiogenesis in gastric cancer to determine its potential as a prognostic biomarker. A total of 119 patients with gastric cancer who had undergone gastrectomy at the 940th Hospital of the Joint Security Force between 2014 and 2018 were included in this study. We assayed the protein expression of YKL-39, CD68, and CD34 by immunohistochemistry in tissues of 119 patients with gastric cancer, as well as the intracellular expression of YKL-39 and CD68 by immunofluorescence. Data were analyzed with SPSS Statistics 25.0 to explore the impact of expression of YKL-39, CD68, and CD34 in gastric cancer patients and the relationship among them. Our results show that YKL-39 was expressed in both the nucleus and cytoplasm of gastric cancer cells and tumor mesenchyme. YKL-39 protein expression was associated with the depth of tumor infiltration, lymph node metastasis, and TNM stage; CD68 protein expression was associated with lymph node metastasis and TNM stage; CD34 protein expression was not associated with clinicopathological characteristics. Expression of YKL-39 was positively correlated with CD68 and CD34 (p < 0.001), and high expression of YKL-39 was associated with poor prognosis (p < 0.05). In gastric cancer, YKL-39 expression is positively correlated with the degree of tumor-associated macrophage infiltration and angiogenesis, and is a potential prognostic marker for gastric cancer.

Considerable evidence suggests that N6-methyladenosine (m6A) is involved in the regulation of long non-coding RNA (lncRNA), whichparticipates in the occurrence, development and prognosis of tumorscancerBut the relationship between m6A regulators-related lncRNA (mRlncRNA) and lung adenocarcinoma (LUAD) remains unclear. This study aims to determine a feature based on mRlncRNA for prognostic evaluation of LUAD patients. By integrating the gene expression data of LUAD and normal samples from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, the m6A gene and mRlncRNA with imbalanced expression were screened out. Then we used the least absolute shrinkage and selection operator (LASSO) to obtain the 13-lncRNA prognostic signature in the TCGA training cohort. Patients were divided into two risk groups based on the risk score of lncRNAs characteristics, and their overall survival (OS) was significantly different. The predictive power of this signature was verified in TCGA testing cohort and entire TCGA cohort. These landmark lncRNAs were involved in several biologiocal processes and pathways related to cell cycle, DNA replication, P53 signaling pathway and mismatch repair. Besides, the high-risk group was low-response to cisplatin, while high-response to mitomycin, docetaxel and immunotherapy. In conclusion, we identified a 13-mRlncRNA model associated with prognosis and treatment sensitivity in LUAD, which may provide clues about the influence of m6A on lncRNA in LUAD and promote the further improvement of LUAD individualized treatment strategies.

INTRODUCTION:In our previous study, it has been confirmed that formaldehyde (FA) not only inhibits the proliferative activity, but also causes DNA-protein crosslinks (DPCs) formation in bone marrow mesenchymal stem cells (BMSCs). The purpose of this study was to detect the protective effect of astragalus polysaccharide (APS) against the cytotoxicity and genotoxicity of BMSCs exposed to FA, and to explore potential molecular mechanisms of APS activity.MATERIAL AND METHODS:Human BMSCs were cultured in vitro and randomly divided into control cells (Ctrl group), FA-treated cells (FA group, 120 μmol/L), and cells incubated with FA and increasing concentrations (40, 100, or 400 μg/mL) of APS (FA + APS groups). Cytotoxicity was measured by MTT assay. DNA strand breakage, DNA-protein crosslinks (DPCs), and micronucleus formation were respectively detected by comet assay, KCl-SDS precipitation assay, and micronucleus assay. The mRNA and protein expression level of xeroderma pigmentosum group A (XPA), xeroderma pigmentosum group C (XPC), excision repair cross-complementation group 1 (ERCC1), replication protein A1 (RPA1), and replication protein A2 (RPA2) were all detected by qRT-PCR and Western Blot.RESULTS:Compared with the FA group, the cytotoxicity, DNA strand breakage, DPCs, and micronucleus levels were decreased significantly in FA + APS groups (P < 0.01). Meanwhile, the mRNA and protein expression of XPA, XPC, ERCC1, RPA1, and RPA2 were up regulated significantly in the FA + APS groups (P < 0.05) with the most prominent effect of the 100 μg/mL APS.CONCLUSIONS:Our results suggest that APS can protect the cytotoxicity and genotoxicity of human BMSCs induced by FA. The mechanism may be associated with up-regulated expression of XPA, XPC, ERCC1, RPA1, and RPA2 in the nucleotide excision repair (NER) pathway which promotes DNA damage repair.

目的:研究敦煌古方平胃丸联合顺铂对SCG-7901胃癌荷瘤小鼠的抑瘤作用及对肾脏毒性影响,探讨敦煌平胃丸联合顺铂对降低肾毒性的作用机制.方法:建立小鼠SCG-7901胃癌皮下荷瘤模型,接种第8 d随机分为模型对照组、顺铂2×10-3 g/kg组、平胃丸14.04 g/kg+顺铂2×10-3 g/kg组、平胃丸14.04 g/kg组,连续给药10 d,隔日小鼠称重并观察一般情况;末次给药后剥取肿瘤、肾,计算抑瘤率和肾指数,苏木素-伊红(HE)染色观察肾组织病理变化;检测血清中肌酐(Scr)、尿素氮(BUN)含量,肾组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量;蛋白免疫印迹法(Western blot)和实时荧光定量聚合酶链式反应(Real-time PCR)分别检测肾组织核因子E2相关因子2(Nrf2)、血红素氧合酶-1(HO-1)蛋白和mRNA的表达.结果:接种后第12 d开始,与模型对照组比较,顺铂2×10-3 g/kg、平胃丸14.04 g/kg+顺铂2×10-3 g/kg组体质量明显下降(P＜0.05或P＜0.01),与顺铂2×10-3 g/kg组比较,平胃丸14.04 g/kg+顺铂2×10-3 g/kg组体质量明显升高(P＜0.05或P＜0.01);顺铂2×10-3 g/kg、平胃丸14.04 g/kg+顺铂2x 10-3 g/kg、平胃丸14.04 g/kg组抑瘤率分别为63.84％、70.57％和30.74％,瘤重均较模型对照组显著降低(P＜0.01),与模型对照组比较,各给药组肾脏均有不同程度病理损伤,其中,顺铂2×10-3 g/kg组最为明显;顺铂2×10-3 g/kg组肾指数、Scr、BUN和MDA含量显著升高(P＜0.01),SOD活性、Nrf2、HO-1蛋白和mRNA表达显著下降(PP＜0.01).与顺铂2×10-3 g/kg组比,平胃丸14.04 g/kg+顺铂2×10-3 g/kg组肾指数、Scr、BUN和MDA含量明显下降(P＜0.05或P＜0.01),SOD活性、Nrf2、HO-1蛋白和mRNA表达显著升高(P＜0.05或P＜0.01).结论:敦煌平胃丸与顺铂单独和联合使用均对SCG-7901胃癌荷瘤小鼠具有抑瘤作用;敦煌平胃丸联合顺铂可能通过激活Nrf2/HO-1信号通路,增强细胞抗氧化应激能力,从而降低顺铂对肾脏的毒性损伤,起到减毒作用.