目的   免疫球蛋白A肾病（IgAN）与炎症性肠病（IBD）的相互作用机制尚未阐明。本研究旨在解析IBD与IgAN共病的关键特征基因及核心信号通路，以揭示肠－肾轴的分子调控网络。方法   于GEO数据库获取IBD（GSE75214）和IgAN（GSE93798）基因表达谱，筛选差异表达基因（DEGs）。通过蛋白互作网络（PPI）和拓扑算法（MCC、MNC、Degree、EPC等）识别核心特征基因，并结合公共数据库（CTD、DISEASES和GeneCards）和单细胞转录组测序（GSE171314）进行验证。通过Nephroseq数据库验证基因表达与临床表型的相关性。结果   共筛选出17个IBD-IgAN共病DEGs，PPI网络分析等确定以FOS、EGR1、CXCL2和JUNB为核心特征基因。功能富集分析显示白细胞介素-17（IL-17）信号通路显著激活。单细胞测序验证FOS、EGR1、CXCL2和JUNB基因在IgAN特异性高表达，并通过Nephroseq数据库验证其与尿蛋白和估算的肾小球滤过率下降（eGFR）显著相关。结论  本研究揭示IBD与IgAN共享IL-17通路异常激活及FOS、EGR1、CXCL2和JUNB的基因网络，为开发基于肠－肾轴调控的靶向治疗策略提供理论依据。

       Objective  The complex interplay between immunoglobulin A nephropathy（IgAN）and inflammatory bowel disease（IBD）remains poorly understood．This  study  aimed to identify  key  cross-talk  genes  and  pivotal  signaling pathways shared between IBD and IgAN，thereby elucidating the molecular regulatory network underlying the gut-kidney axis．Methods  Transcriptomic datasets for IBD（GSE75214）and IgAN（GSE93798）were retrieved from the GEO database．Differentially expressed genes（DEGs）were screened，and shared DEGs were intersected．Protein-protein interaction（PPI）networks were constructed using STRING and Cytoscape，with topological algorithms applied to identify hub genes．Gene expression profiles were validated through（CTD，DISEASES and GeneCards）and single-cell RNA sequencing（GSE171314）and the Nephroseq database，focusing on clinical correlations with proteinuria and estimated glomerular filtration rate（eGFR）．Results  Seventeen shared DEGs were identified between IBD and IgAN．PPI network analysis revealed FOS，EGR1，CXCL2 and JUNB as core hub genes．Functional enrichment analysis demonstrated significant activation of the interleukin-17（IL-17）signaling pathway．Single-cell sequencing confirmed the specific upregulation of these genes in renal tubular epithelial cells of IgAN patients，which was further validated to correlate with proteinuria and eGFR decline．Conclusions  IBD and  IgAN share aberrant activation of the IL-17 pathway and a co-regulatory gene network involving FOS，EGR1，CXCL2 and JUNB，providing a theoretical foundation for developing therapeutic strategies centered on the gut-kidney axis．

目的 探讨重楼皂苷Ⅰ（PPI）对慢性髓系白血病细胞（K562）细胞的抑制作用及可能的作用机制。方法 采用CCK-8法筛选药物最适浓度,将培养时间为24 h的药物最适浓度作为后续实验的干预浓度。分组如下：（1）空白组;（2）PPI组;（3）抑制剂组;（4）PPI+抑制剂组。采用CCK-8法检测细胞增殖率;AO/EB染色观察细胞形态;流式细胞术检测凋亡率;ROS检测试剂盒检测活性氧（ROS）含量、还原型谷胱甘肽含量检测试剂盒检测谷胱甘肽（GSH）含量、细胞亚铁比色法测试盒检测细胞亚铁（Fe²⁺）含量;qRT-PCR法和蛋白免疫印迹法检测各组肿瘤蛋白53（p53）、钠氯离子依赖性氨基酸转运蛋白11（SLC7A11）、谷胱甘肽过氧化物酶4（GPX4）mRNA及蛋白表达量。结果 PPI抑制K562细胞的生长,且呈一定的剂量及时间依赖性（与同时间段的对照组0μmol/L比较,均P<0.01）。与空白组相比,PPI抑制K562细胞的增殖,提高了凋亡率,而铁死亡抑制剂（Ferrostian-1）的使用逆转了PPI对K562凋亡的促进作用（P<0.01）。与空白组相比,PPI组ROS、Fe²⁺含量升高,GSH含量下降,而铁死亡抑制剂的使用可下调ROS、Fe²⁺,上调GSH的含量（P<0.01）。PPI组较空白组p53 mRNA和蛋白表达水平升高,而SLC7A11、GPX4 mRNA和蛋白表达水平下降（P<0.05）;PPI+抑制剂组细胞较重楼皂苷组p53 mRNA和蛋白表达水平下降,而SLC7A11、GPX4 mRNA和蛋白表达水平升高（P<0.05）。结论 PPI能够有效抑制K562细胞增殖,促进K562细胞铁死亡,其分子机制可能与p53信号通路的调控有关。

Objective To investigate the inhibitory effect of polyphyllin I（PPI）on chronic myeloid leukemia cells（K562）and its possible mechanism．Methods K562 cell line was cultured in suitable environment,and the optimal concentration of the drug was screened by CCK-8 method．The optimal concentration of the drug cultured for 24 hours was used as the intervention concentration of the follow-up experiment．Cells were divided into the following groups：（1）blank group,（2）saponins group,（3）inhibitor group and（4）saponins + inhibitor group．The cell proliferation rate was detected by CCK-8 method．The cell morphology was observed by AO/EB staining．The apoptosis rate was detected by flow cytometry．The contents of reactive oxygen species（ROS）,glutathione（GSH）and ferrous（Fe²⁺）in different groups were detected,and the expression of mRNA and protein in different groups were detected by qRT- PCR and Western blot respectively．Results PPI significantly inhibited the growth of K562 cells in a dose-and time-dependent manner．Compared with the blank group,PPI significantly inhibited the proliferation of K562 cells and increased the apoptosis rate of K562 cells,while the use of ferroptosis inhibitor（Ferrostian-1）reversed the promoting effect of PPI on apoptosis of K562 cells．Compared with the blank group,the contents of reactive oxygen species（ROS）and ferrous iron（Fe²⁺）increased and the content of glutathione（GSH）decreased in the saponins group．The use of Ferrostian-1 could down-regulate the contents of ROS and Fe²⁺ and increase the content of GSH in the cells treated with the drug．Compared with the blank group,the expression of p53 mRNA and protein in the saponins group increased,while the expression of SLC7A11,GPX4 mRNA and protein decreased．The expression of p53 mRNA and protein in the saponins + inhibitor group was lower than that in the saponins group,while the expression levels of SLC7A11,GPX4 mRNA and protein increased．Conclusions PPI can effectively inhibit the proliferation of K562 cells and promote ferroptosis in K562 cells．The molecular mechanism can be related to the regulation of p53 signal pathway．

Wnt/β-catenin信号通路是一种在胚胎发育,细胞增殖分化、迁移,干细胞更新等中起关键作用的蛋白质家族。Wnt/β-catenin信号通路的失调常常会导致各种严重的疾病,例如肿瘤、心脏疾病、肺部疾病、肝脏疾病、骨骼疾病、神经疾病等。大量研究表明,Wnt/β-catenin信号通路在心肌纤维化发病机制中起重要作用,本文结合最新研究成果,从心肌纤维化相关疾病的角度对Wnt/β-catenin通路进行综述,为预防心肌纤维化提供新的思路,进一步达到防治心血管疾病的目的。

The Wnt/β-catenin signaling pathway is a family of proteins that play a key role in embryonic development,cell proliferation and differentiation,migration,stem cell renewal,etc．Dysfunctions of Wnt/β-catenin signaling pathway often lead to various serious diseases,such as tumor,heart,lung,liver,bone and neurological diseases,etc．Numerous studies have shown that the Wnt/β-catenin signaling pathway plays an important role in the pathogenesis of cardiac fibrosis．This article,in combination with the latest research findings,presents a review of the Wnt/β-catenin pathway from the perspective of myocardial fibrosis-related diseases,in order to provide new ideas for preventing myocardial fibrosis and achieving the goal of combating cardiovascular disease．

慢性萎缩性胃炎是常见的胃癌前病变,不仅治疗过程漫长,治疗难度大,而且患者依从性欠佳。不仅会对患者的生理、心理健康和生活质量造成严重不良的影响,还会给患者家属造成负担,成为临床上不可忽视的难题。但是本病发病机制目前尚未完全明确,临床治疗还未达成共识。文章综述了近10年基于Hedgehog信号通路的中医药干预慢性萎缩性胃炎的研究概况。中医药调控Hedgehog信号通路辨证论治是治疗慢性萎缩性胃炎的一种独具特色的疗法,近年来有关基于Hedgehog信号通路的中医药干预治疗慢性萎缩性胃炎的报道越来越多。文章主要通过遵循疾病本虚标实的病性,以脾胃虚弱为本,瘀血、气滞、湿热、痰浊等为标,探讨选方治疗对慢性萎缩性胃炎的影响,认为中医药联合Hedgehog信号通路实行现代化发展能够有效干预治疗慢性萎缩性胃炎,以期为进一步临床研究与应用提供参考。

Chronic atrophic gastritis,a common precancerous lesion of gastric cancer,requires a long-term treatment and is difficult to cure．Therefore,it usually leads to decreased patient compliance．It will not only have a serious adverse impact on the patient’s physical and mental health and quality of life,but also cause a burden to the patient’s family,which has become a difficult problem that can not be ignored clinically．However,the pathogenesis has not yet been totally clarified,not to mention a consensus on the clinical treatment．This paper reviews the research revolving around Chinese medicine intervention in chronic atrophic gastritis based on the Hedgehog signaling pathway in the last decade．It’s creative therapy of chronic atrophic gastritis that utilizing Traditional Chinese Medicine to regulate and control Hedgehog signaling pathway,which has been increasingly reported in recent years．This paper is based on “deficiency in origin” and “excess in superficiality” principle．Concretely,spleen-stomach vacuity is characterized by deficiency in origin,and excess in superficiality manifests blood stasis,qi stagnation,dampness-heat and phlegm turbidity as excess in superficiality．By this way,the paper explores the effect of prescription selection on chronic atrophic gastritis．It is believed that the modern therapy that combines traditional Chinese medicine with Hedgehog signaling pathway can tackle chronic atrophic gastritis,thus providing a reference for further clinical trials and practices．

目的 探讨核结合蛋白2(NUCB2)介导的下游信号分子和通路,为阐明NUCB2在乳腺癌中的功能提供依据。方法 构建NUCB2-RNAi慢病毒载体,感染MDA-MB-231细胞株。然后将MDA-MB-231分为阴性对照病毒感染细胞组(NC组)、感染NUCB2基因shRNA病毒细胞组(KD组),用Affymetrix基因表达谱芯片对NUCB2下游基因进行筛选,并对所有数据进行独创性通路分析(IPA)分析。用qPCR测定mRNA水平。统计采用SPSS 20.0软件。结果 Path-Array研究筛选了KD组与NC组的差异基因,其中上调基因186个,下调基因356个,部分差异表达基因的检测表明,这些基因的mRNA水平与Path-Array筛选结果一致。IPA分析显示,经典途径中差异表达基因的显著富集表明胆固醇生物合成的超途径被显著抑制。上游调节因子分析显示了所有不同表达基因的上游调节因子,包括转录因子、细胞因子、小RNA、受体、激酶、化学分子和药物。疾病和功能差异表达基因的显著丰富表明,与NUCB2相关的差异表达基因与41种疾病和功能显著相关,更多与癌症、组织损伤和异常相关。结论 NUCB2的功能涉及多种基因和多种信号通路。

Objective In order to further explore the downstream signal molecules and pathways mediated by nucleobindin-2 (NUCB2), to provide a basis for elucidating the significance of NUCB2 in breast cancer. Method NUCB2-RNAi lentivirus vector was constructed and infecting MDA-MB-231 cell line.Then MDA-MB-231 cells were divived into two group, cells with negative control virus infection (NC group) and cells infected with NUCB2 gene shRNA virus (KD group). NUCB2 downstream gene screening was conducted by Affymetrix gene expression profiling Path-Array chip and all data were analyzed by ingenuity pathway analysis (IPA). The mRNA level was detected by qPCR. SPSS 20.0 software was used for statistics. Results Path-Array study screened out differential genes between KD and NC group which the number of up-regulated genes was 186, the number of down-regulated genes was 356.Detection of some differentially expressed genes showed that the mRNA levels of these genes were consistent with the results of Path-Array screening.IPA analysis revealed that significant enrichment of differentially expressed genes in the classical pathway showed superpathway of cholesterol biosynthesis was significantly inhibited.The upstream regulatory factor analysis showed the upstream regulatory factors of all the differentially expressed genes, including transcription factors, cytokine, small RNA, receptors, kinases, chemical molecules and drugs.The significant enrichment of differentially expressed genes in disease and function showed that NUCB2 associated differentially expressed genes were significantly related with 41 diseases and functions, which were more related with cancer, organismal injury and abnormities. Conclusion The function of NUCB2 involved multiple genes and multiple signaling pathways.

目的 探讨血必净注射液对SAP大鼠TLR4信号通路介导肠黏膜屏障功能障碍的影响。方法 24只SD大鼠随机分成空白组(n=8)、对照组(n=8)和治疗组(n=8)。对照组和治疗组用4.5%牛磺胆酸钠溶液胆胰管逆行注射制备SAP模型,空白组采用等量生理盐水逆行注射。治疗组在造模3 h后经鼠尾静脉注射血必净注射液(3 mL/kg)。三组大鼠造模后观察24 h,然后处死取胰腺和小肠组织送病理检查,采用荧光RT-PCR技术检测TLR4和NF-κB表达水平,采用ELSIA法检测血清TNF-α、IL-6、淀粉酶(AMS)及二胺氧化酶(DAO)水平,比较三组大鼠各项指标。结果 对照组和治疗组小肠组织TLR4和NF-κB表达以及血清TNF-α、IL-6、AMS及DAO水平均高于空白组(P>0.05),治疗组小肠组织TLR4和NF-κB表达以及血清TNF-α、IL-6、AMS及DAO水平低于对照组(P＜0.05)。结论 血必净注射液通过干预SAP大鼠TLR4信号通路,降低小肠组织TLR4和NF-κB的表达,减轻小肠组织的炎症反应,对肠黏膜屏障具有一定的保护作用。

Objective To investigate the effect on intestinal mucosal barrier dysfunction (IBF) of Xuebijing injection mediated by Toll-like receptor 4 (TLR4) signal pathway in rats of severe acute pancreatitis (SAP). Methods 24 Sprague Dawley (SD) rats were randomly divided into Sham group (n=8), control group (n=8) and treatment group (n=8). The SAP model was established by retrograde injection of 4.5% sodium taurocholate into the biliopancreatic duct in control group and treatment group, while control group was injected with the same amount of saline. In treatment group, Xuebijing injection (3 mL/kg) was injected via tail vein after 3h of modeling. All rats were monitored and sacrificed after 24 hours of modeling. Samples of pancreas and intestine were collected for pathologic determination. A fluorescent RT-PCR was used to determine the expression of TLR4 and NF-κB of small intestine. The serum levels of TNF-α, IL-6, amylase (AMS) and diamine oxidase (DAO) were measured by using ELISA. All parameters of three groups were compared. Results The expression of TLR4 and NF-κB of small intestine in control group and treatment group were higher than it in control group (P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO (P<0.05). The expression of TLR4 and NF-κB of small intestine in treatment group were lower than it in control group (P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO (P<0.05). Conclusion Xuebijing injection may not only reduce the expression of TLR4 and NF-κB of small intestine, but also alleviate the inflammation reaction of small intestine by interfering with TLR4 signal pathway, which may have a protective effect on intestinal mucosal barrier in SAP rats.

目的 在原来研究的基础上进一步研究Wnt-1信号通路蛋白-3（WISP-3）在高氧诱导肺上皮细胞凋亡中的作用。方法 通过Western blot检测和免疫组化检测不同肺上皮细胞中WISP-3的蛋白表达量。利用质粒转染和siRNA的方法在Beas-2B细胞中高表达和基因沉默WISP-3,通过细胞活性检测和流式细胞学技术检测高氧刺激后细胞的凋亡情况。结果 与空气对照相比,高氧刺激使肺上皮细胞的WISP-3蛋白表达量下降;WISP-3基因沉默或高表达使高氧诱导的肺上皮细胞凋亡增加或减少。结论 高氧刺激下,肺上皮细胞中WISP-3表达下降,WISP-3对高氧诱导的肺上皮细胞凋亡具有保护作用。

Objective To explore how Wnt-1 inducible signaling pathway protein-3 （WISP-3） participate in and play a regulatory role in the process of hyperoxia induced apoptosis in lung epithelial cells. Methods The expression of WISP-3 was detected via Western blot and immunohistochemistry. High expression and low expression of WISP-3 were performed by plasmid transfection and siRNA. Cell viability and flow cytometry were executed to detect the hyperoxia-induced apoptosis in Beas-2B. Results Compared to the group of air control,the expression of WISP-3 protein in lung epithelial cells decreased obviously after hyperoxia. Cell survival decrease and apoptosis increased after hyperoxia in Beas-2B cells with low expression of WISP-3. Vice versa. Conclusion The expression of WISP-3 decreased after hyperoxia in lung epithelial cells. The role of WISP-3 in this process may be protective.

目的 初步探讨黄芩苷防治支气管哮喘的作用机理。方法 用卵蛋白致敏大鼠制备支气管哮喘动物模型,经黄芩苷干预治疗,运用免疫组化法及Western Blot法检测各组大鼠肺组织匀浆中p38 MAPK磷酸化蛋白表达量。结果 两种检测方法均显示,p38 MAPK磷酸化蛋白水平在模型组中有明显的增加,地塞米松组、黄芩苷高剂量组和低剂量组的p38 MAPK磷酸化蛋白水平均低于模型组(P<0.05)。结论 黄芩苷能有效治疗哮喘的作用与抑制哮喘大鼠p38 MAPK信号通路的表达密切相关。

Objective To explore the mechanism of Baicalin in treatment of bronchia asthma. Methods Animal models of bronchia asthma were made in rats sensitized with egg albumen. After the treatment of Baicalin, immunohistochemistry and western-blot methods were used to test expression quantity of phosphorylated p38 protein of lung tissue in all groups of guinea rats. Results Our data confirmed that the level of phosphorylated p38 protein increased significantly in model group, but it decreased in hexadecadrol group, high dose and low dose Baicalin group (P<0.05). Conclusion The effects of Baicalin in asthma model were associated with inhibition of P38 MAPK signal pathways in a dose-dependent manner.

       目的  探讨重楼皂苷Ⅰ（PPI）对慢性髓系白血病细胞（K562）细胞的抑制作用及可能的作用机制。方法  采用CCK-8法筛选药物最适浓度，将培养时间为24 h的药物最适浓度作为后续实验的干预浓度。分组如下：（1）空白组；（2）PPI组；（3）抑制剂组；（4）PPI+抑制剂组。采用CCK-8法检测细胞增殖率；AO/EB染色观察细胞形态；流式细胞术检测凋亡率；ROS检测试剂盒检测活性氧（ROS）含量、还原型谷胱甘肽含量检测试剂盒检测谷胱甘肽（GSH）含量、细胞亚铁比色法测试盒检测细胞亚铁（Fe²⁺）含量；qRT-PCR法和蛋白免疫印迹法检测各组肿瘤蛋白53（p53）、钠氯离子依赖性氨基酸转运蛋白11（SLC7A11）、谷胱甘肽过氧化物酶4（GPX4）mRNA及蛋白表达量。结果  PPI抑制K562细胞的生长，且呈一定的剂量及时间依赖性（与同时间段的对照组0μmol/L比较，均P＜0.01）。与空白组相比，PPI抑制K562细胞的增殖，提高了凋亡率，而铁死亡抑制剂（Ferrostian-1）的使用逆转了PPI对K562凋亡的促进作用（P＜0.01）。与空白组相比，PPI组ROS、Fe²⁺含量升高，GSH含量下降，而铁死亡抑制剂的使用可下调ROS、Fe²⁺，上调GSH的含量（P＜0.01）。PPI组较空白组p53 mRNA和蛋白表达水平升高，而SLC7A11、GPX4 mRNA和蛋白表达水平下降（P＜0.05）；PPI+抑制剂组细胞较重楼皂苷组p53 mRNA和蛋白表达水平下降，而SLC7A11、GPX4 mRNA和蛋白表达水平升高（P＜0.05）。结论  PPI能够有效抑制K562细胞增殖，促进K562细胞铁死亡，其分子机制可能与p53信号通路的调控有关。

       Objective  To investigate the inhibitory effect of polyphyllin I（PPI）on chronic myeloid leukemia cells（K562）and its possible mechanism．Methods  K562 cell line was cultured in suitable environment，and the optimal concentration of the drug was screened by CCK-8 method．The optimal concentration of the drug cultured for 24 hours was used as the intervention concentration of the follow-up experiment．Cells were divided into the following groups：（1）blank group，（2）saponins group，（3）inhibitor group and（4）saponins + inhibitor group．The cell proliferation rate was detected by CCK-8 method．The cell morphology was observed by AO/EB staining．The apoptosis rate was detected by flow cytometry．The contents of  reactive oxygen species（ROS），glutathione（GSH）and ferrous（Fe²⁺）in different groups were detected，and the expression of mRNA and protein in different groups were detected by qRT- PCR and Western blot respectively．Results  PPI significantly inhibited the growth of K562 cells in a dose-and time-dependent manner．Compared with the blank group，PPI significantly inhibited the proliferation of K562 cells and increased the apoptosis rate of K562 cells，while the use of ferroptosis inhibitor（Ferrostian-1）reversed the promoting effect of PPI on apoptosis of K562 cells．Compared with the blank group，the contents of reactive oxygen species（ROS）and ferrous iron（Fe²⁺）increased and the content of glutathione（GSH）decreased in the saponins group．The use of Ferrostian-1 could down-regulate the contents of ROS and Fe²⁺ and increase the content of GSH in the cells treated with the drug．Compared with the blank group，the expression of p53 mRNA and protein in the saponins group increased，while the expression of SLC7A11，GPX4 mRNA and protein decreased．The expression of p53 mRNA and protein in the saponins + inhibitor group was lower than that in the saponins group，while the expression levels of SLC7A11，GPX4 mRNA and protein increased．Conclusions  PPI can effectively inhibit the proliferation of K562 cells and promote ferroptosis in K562 cells．The molecular mechanism can be related to the regulation of p53 signal pathway．