Ulcerative colitis (UC) is one of the most important chronic inflammatory bowel diseases (IBD), and the aetiology of UC involves the interplay of genetic susceptibility, immune dysregulation, gut microbes and environmental factors. The cAMP response element modulator (CREM), a major effector of cAMP signalling, is a key transcription factor belonging to the cAMP response element binding protein (CREB) family. It integrates multiple upstream signaling pathways with distinct functions, such as cAMP/PKA, Ca2+/CaMKIV and AKT/mTOR. According to the urgent research, aberrant CREM expression occurs in colonic mucosal tissues and immune cells of UC patients which suggests its significant role in UC pathogenesis through multiple mechanisms. This review systemically summarizes the basic biological features of CREM, which comprises structural characteristics, isoform diversity, and regulatory networks in cellular signaling. In addition, we systematically analyse the main mechanisms by which CREM facilitates UC including the functions of immune cells, T cells, B cells and NK cells. Then we discuss the balance between pro-inflammatory and anti-inflammatory cytokines and the impact on intestinal barrier and gut microbiota. Ultimately, we will address the emerging resources, clinical potential of CREM as a healing target and pathway for future research. The purpose of this review is to provide novel insights into the pathogenesis of UC, which may contribute to optimizing clinical treatment and developing new therapeutic drugs.

BackgroundUlcerative colitis (UC) is an inflammatory bowel disease characterized by persistent colonic inflammation. Here, we performed a systematic analysis to gain better insights into UC pathogenesis.MethodsWe analyzed two UC-related datasets extracted from the gene expression omnibus database using several bioinformatics tools. The primary cell types and key subgroups of primary cells associated with UC and differentially expressed genes (DEGs) between UC and control samples were identified. The molecular regulation of the key genes was also predicted. The gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses of marker genes of key cell subgroups and model genes were performed. The expression of key enriched genes was validated in 10 clinical samples using real-time quantitative polymerase chain reaction (RT-qPCR).ResultsMonocytes were identified as the major cell type. Ten differentially expressed marker genes were obtained by intersecting the 3121 DEGs, 38 marker genes in major cell types, and 104 marker genes in key cell subgroups. Four essential genes, associated with immune response, were obtained using support vector machine recursive feature elimination and least absolute shrinkage and selection operator analyses. The four essential genes were highly expressed in Cluster 0 during differentiation. Validation of the four key genes in colonic mucosal biopsy specimens from 10 normal and 10 UC patients revealed that CREM was highly expressed in both the lesion-free sites and lesion sites colonic mucosa of UC patients compared with normal adults.ConclusionsWe identified CREM involved in UC pathogenesis, which is expected to provide a new therapeutic target for UC.

BACKGROUND:Chronic Kidney Disease (CKD) leads to structural and functional abnormalities of the kidneys and seriously jeopardizes human health. Shenyan Oral Liquid (SOLI), a Chinese medicinal preparation, has been reported to protect podocytes in patients with chronic kidney disease (CKD). OBJECTIVE:The objective of this study is to investigate the mechanism of action of the Chinese medicinal preparation Senyan Oral Liquid (SOLI) in the treatment of CKD by protecting podocytes through network pharmacology technology and experimental validation. METHODS:Compounds of SOLI and targets of CKD disease were collected and screened. The SOLI network of bioactive compounds targeting CKD and the protein-protein interaction (PPI) network were constructed using Cytoscape software and the STRING online database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the R software Cluster Profiler package. Molecular docking was performed using Autodock software to verify the binding ability of bioactive compounds and target genes. Subsequently, the potential mechanism of SOLI on CKD predicted by network pharmacological analysis was experimentally studied and verified in an adriamycin-induced nephropathy rat model. RESULTS:A total of 81 targets of SOLI components acting on CKD were identified. The results of the PPI analysis clarified that five key target genes (TNF, AKT1, IL6, VEGFA, and TP53) play a critical role in the treatment of CKD by SOLI. The GO analysis and KEGG enrichment analysis indicated that SOLI acts through multiple pathways, including the PI3K/AKT signaling pathway against CKD. Molecular docking showed that the main compounds of SOLI and five key genes had strong binding affinity. In a rat model of adriamycin-induced nephropathy, SOLI significantly ameliorated disease symptoms and improved renal histopathology. Mechanistic studies showed that SOLI upregulated the expression level of Nephrin, inhibited the PI3K/AKT pathway in renal tissues, and ultimately suppressed the activation of autophagy-related proteins in CKD. CONCLUSION:SOLI exerted a renoprotective effect by regulating the Nephrin-PI3K/AKT autophagy signaling pathway, and these findings provide new ideas for the development of SOLI-based therapeutic approaches for CKD.

Abstract Background Huangkui Lianchang Decoction (HLD) is a traditional Chinese herbal formula for treating ulcerative colitis (UC). However, its mechanism of action remains poorly understood. The Study aims to validate the therapeutic effect of HLD on UC and its mechanism by integrating network pharmacology, bioinformatics, and experimental validation. Methods UC targets were collected by databases and GSE19101. The active ingredients in HLD were detected by ultra-performance liquid chromatography-tandem mass spectrometry. PubChem collected targets of active ingredients. Protein–protein interaction (PPI) networks were established with UC-related targets. Gene Ontology and Kyoto Encyclopedia (KEGG) of Genes and Genomes enrichment were analyzed for the mechanism of HLD treatment of UC and validated by the signaling pathways of HLD. Effects of HLD on UC were verified using dextran sulfate sodium (DDS)-induced UC mice experiments. Results A total of 1883 UC-related targets were obtained from the GSE10191 dataset, 1589 from the database, and 1313 matching HLD-related targets, for a total of 94 key targets. Combined with PPI, GO, and KEGG network analyses, the signaling pathways were enriched to obtain IL-17, Toll-like receptor, NF-κB, and tumor necrosis factor signaling pathways. In animal experiments, HLD improved the inflammatory response of UC and reduced UC-induced pro-inflammatory factors such as Tumor Necrosis Factor Alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). HLD suppressed proteins TLR4, MyD88, and NF-κB expression. Conclusions This study systematically dissected the molecular mechanism of HLD for the treatment of UC using a network pharmacology approach. Further animal verification experiments revealed that HLD inhibited inflammatory responses and improved intestinal barrier function through the TLR4/MyD88/NF-κB pathway.

目的 了解本院肿瘤科患者程序性死亡受体1(PD-1)抑制剂的临床应用与不良反应.方法 回顾性收集2020年1月—2021年12月在本院肿瘤内科使用PD-1抑制剂患者的临床资料,分析患者的基本信息、用药医嘱、联合治疗方案、影像学评价结果及不良反应.结果 55例患者中,男33例,女22例,平均年龄(63.26±11.23)岁,使用PD-1抑制剂共241次;病理诊断主要为肺癌27例(49.09％)、肝癌10例(18.18％)、食管癌3例(5.45％)和宫颈癌3例(5.45％)等;最常见的抗肿瘤方案是化疗联合免疫治疗、免疫治疗、靶向联合免疫治疗;使用频率较高是信迪利单抗200 mg的3周1次方案、卡瑞利珠单抗200 mg的3周1次和2周1次方案;44例患者发生药品不良反应,较为常见的是自身免疫性疾病(34.54％)、骨髓抑制(20.00％)和全身乏力(10.91％).结论 PD-1抑制剂在本院肿瘤科的使用仍处于探索阶段,临床药师应积极配合临床医生做好药学监护工作.

目的:分析医院住院患者的人血白蛋白使用情况,为人血白蛋白在临床的合理使用提供参考.方法:随机抽取 2020 年 1 月—12 月南京中医药大学苏州附属医院收治的 240 例(每月 20 例)使用人血白蛋白治疗的住院患者作为研究对象,采集患者的年龄、性别、所在科室、用药原因和用药前的血清白蛋白(albumin,ALB)水平等信息,并依据相关指南、共识和药品说明书等资料进行合理用药评价.结果:240 例使用人血白蛋白治疗的住院患者中,男女比例相当(121 例vs 119 例),年龄上主要集中在＞60～80 岁(128 例,占 53.33%)和＞80 岁(占26.67%),在科室分布上前 5 位的依次为骨伤科(40 例,占 16.67%)、血液科(32 例,占 13.33%)、肾内科(31 例,占 12.92%)、脾胃病科(30 例,占 12.50%)和ICU(22 例,占 9.17%);在用药原因方面,主要的原因为低蛋白血症(124 例,占 51.67%),其次为肝肾疾病导致的水肿(38 例,占 15.83%)、营养支持(26 例,占 10.83%)和促进术后切口愈合(26 例,占 10.83%);用药前,患者的ALB水平主要集中在＞25～30 g/L(107 例,占 44.50%),其次为＞20～25 g/L(70 例,占 29.17%);合理用药点评结果显示,240 患者中符合用药适应证的有 171 例(占 71.25%),而存在相关禁忌证的有 94 例(占 39.17%),但无用法用量和联合用药不适宜情况.结论:当前医院住院患者的人血白蛋白使用存在较多的不合理情况,临床可组织本院专家建立人血白蛋白的使用规范,以指导临床合理使用人血白蛋白.

Tumor angiogenesis, which may be affected by microenvironmental inflammation and promotes tumor development and metastasis, is one of the key reasons contributing to increased mortality. The goal of this study is to investigate how lignin analogs, specifically honokiol (HNK), block angiogenesis induced by the inflammatory milieu of lung cancer. The human lung cancer cell lines A549 and H460 were treated with HNK. Interleukin-1 was employed to mimic an inflammatory tumor microenvironment. Findings demonstrated that HNK drastically decreased the cell viability of A549 and H460 cells. In A549 and H460 cells, HNK also reduced the production of vascular endothelial growth factor (VEGF), the most important marker of tumor angiogenesis. Signal pathway studies revealed that HNK blocked the NF-KB signaling pathway. This effect, in turn, prevented the expression of VEGF by inhibiting the NF-KB signaling pathway. Human umbilical vein endothelial cells (HUVECs) from A549-conditioned medium cultures were subjected to HNK treatment, which decreased tubulogenesis, horizontal and vertical migration, and cell proliferation in HUVECs. Overall, HNK inhibited the NF-KB pathway. This effect resulted in the downregulation of VEGF, thus reducing the viability and angiogenesis of human lung cancer cell lines. In A549 cell xenografts, HNK decreased VEGF expression, tumor angiogenesis, and tumor development. Our research shows that HNK is a potential antiangiogenic molecule for the treatment of lung cancer.

Xiben Pills (XBP) are a Chinese medicine prescription with long history of use against lung cancer. Modern pharmacological experiments proved that XBP and its main compounds have anti-tumor effects. However, the mechanism by which XBP inhibits the progression of non-small cell lung cancer remains unclear.This study aimed to explore the potential targets and mechanism of XBP in the treatment of non-small cell lung cancer by network pharmacology and biological experiments.Network pharmacology was used to screen the prospective targets, pathways, and central genes of XBP in the treatment of non-small cell lung cancer. Based on the results of network pharmacology, the active ingredients of XBP were docked with the core target molecules of NSCLC. The viability of A549 and H460 cells was detected by CCK-8 method. Flow cytometry and Hoechst staining were used to detect cell apoptosis and Caspase 3 expressions in each group. Western blot verified the key protein expression underlying XBP’s therapeutic effect on NSCLC. A549 xenograft tumor model was used to evaluate the inhibitory effect of XBP on lung cancer. Apoptotic proteins Bax and Bcl-2 were detected in the tumor by immunohistochemistry.Ninety active ingredients and 191 potential drug targets were screened from XBP. A total of 280 pathways were enriched. Through these analyses, AKT1 was identified as a potential target for XBP to inhibit NSCLC. Molecular docking results showed that XBP ingredients had high affinity with AKT1. XBP significantly inhibited cell proliferation in A549 and H460 in a concentration-dependent manner. XBP induced the apoptosis of A549 cells and increased Caspase 3 expression. XBP significantly increased Bax and Caspase 3 expressions and inhibited Bcl-2 protein level. The mechanism of action was XBP’s inhibition of AKT phosphorylation. Xenograft results showed that XBP could inhibit lung cancer tumor growth and induce tumor cell apoptosis.Our research proved the anti-NSCLC effect of XBP through network pharmacology analysis and experiments. Results give a theoretical basis for XBP’s clinical anti-tumor effect and lay the foundation for further research on XBP.

目的 探讨和厚朴酚(honokiol,HNK)对肿瘤炎性微环境诱导的肺癌细胞H460血管生成的影响及其可能的机制.方法 采用CCK-8检测HNK对H460细胞和人脐静脉内皮细胞(HUVECs)增殖的影响;RT-PCR、Western blot、免疫荧光检测血管内皮生长因子(VEGF)的表达;Western blot检测信号通路蛋白p-IκBα、p-IKKα和NF-κB p65蛋白表达.采用划痕试验、Transwell迁移试验和成管试验检测HNK抑制HUVEC细胞的迁移和血管生成能力.结果 HNK作用H460细胞24、48、72 h后,浓度和时间依赖地抑制H460细胞增殖.HNK能够浓度依赖的抑制HUVEC细胞的存活.HNK还降低了H460细胞中血管内皮生长因子(VEGF)的蛋白质和mRNA表达水平.随后,HNK浓度依赖性地抑制了NF-κB信号通路中IκBα、NF-κB和p-IKKα.划痕试验、Tran-swell小室迁移试验和成管试验显示HNK处理的H460条件培养基具有抑制HUVEC细胞的迁移和血管生成能力.结论 HNK可以通过抑制NF-κB途径导致VEGF的下调而降低人肺癌细胞的活力和血管生成.

目的:建立益气逐瘀利水方的HPLC指纹图谱,并测定4种成分含量,为益气逐瘀利水方产业化开发的质量控制提供参考.方法:采用Agilent ZORBAX Eclipse XDB-C18色谱柱,乙腈-0.1％磷酸水为流动相,梯度洗脱,体积流量1.0 mL·min-1,柱温30℃,检测波长245 nm,建立10批益气逐瘀利水方指纹图谱.采用中药色谱指纹图谱相似度评价软件(2012年版)进行相似度评价,结合聚类分析(CA)、主成分分析(PCA)及正交偏最小二乘法-判别分析(OPLS-DA)模式识别技术进行质量评价,同时进行含量测定.结果:10批益气逐瘀利水方标准汤剂指纹图谱相似度均大于0.995,标定出共有峰24个,指认其中的4个共有峰(14号峰毛蕊异黄酮葡萄糖苷、15号峰阿魏酸、17号峰汉防己乙素、19号峰粉防己碱),CA、PCA及OPLS-DA将10批样品分成2类.定量分析方法学考察结果良好,10批样品中毛蕊异黄酮葡萄糖苷、阿魏酸、汉防己乙素、粉防己碱的定量结果分别为43.98～64.18、107.32～167.95、122.63～175.21、391.62～582.02 μg·g-1.结论:所建立的益气逐瘀利水方指纹图谱及定量测定方法稳定性好、重复性高,可更加全面系统地评价益气逐瘀利水方的质量.

目的 分类讨论中药注射剂功能主治的临床应用,为合理选择中药注射剂提供参考.方法 建立"评分分类法",分别从影响中药注射剂功能主治选择的8个方面对53种中药注射剂进行评分,分类探讨其功能主治在临床具体选用时存在的问题.结果 53种中药注射剂通过"评分分类",分值统计在分别为-2分、-1分、0分、2分、3分、4分、5分、6分、7分组,无一中药注射剂有全部加分.其中4分组15个药,数量最多,占比28.30％;＜4分的有22个药,占比41.51％;＞4分的有16个药,占比30.19％.＜0分(包括0分)有5个药;最高评分是7分,有3个药.结论 中药注射剂说明书上缺乏完整的处方规则说明与现代研究,标注项对临床合理选药的指导尚缺乏一定的内容.

目的:针对利用德尔菲法所构建的中药饮片和中成药重复用药评价标准,对我院门急诊中(成)药处方进行点评,验证该点评标准可行性和实际应用情况,并分析造成重复用药的主次因素.方法:于2020年9～11月期间,抽取我院各科室中存在中药饮片、中成药联合用药处方4500张,依据本点评标准和相关法规要求,点评与分析该标准各条目发生频次及案例.并采用帕累托图分析重复用药主、次因素.结果:4500张处方中,每月平均重复用药累计触发频次达503次.各科室中,以妇科累计触发频次最高,每月147次.针对各问题代码,每月以A1、A2项条目重复用药频次最高,分别占9.60％、9.49％.帕累托图分析结果显示,重复用药处方问题代码中A1、A2、B1、D2项为主要因素,C2项为次要因素.结论:根据点评结果及重复用药典型案例可知,中药饮片和中成药重复用药评价标准有其存在意义,可以为合理用药提供方法学参考.

目的:通过多指标正交试验筛选用煎药机煎煮牡蛎散的最佳工艺,明确工艺参数,为科学煎制牡蛎散提供试验数据.方法:本试验以牡蛎散煎剂中毛蕊异黄酮葡萄糖苷、碳酸钙及浸出物的含量为指标,采用单因素考察和正交试验相结合的方法,选择浸泡时间、煎煮时间、煎煮温度3个因素进行试验,筛选用煎药机煎煮牡蛎散的最佳工艺.结果:采用SPSS 15.0统计学软件进行分析可知,煎煮时间对采用煎药机煎煮牡蛎散有显著影响.确定采用煎药机煎煮牡蛎散的最佳工艺为:将牡蛎散饮片浸泡40 min后,用煎药机在110℃的条件下煎煮30 min.结论:本试验筛选出的用煎药机煎煮牡蛎散的最佳工艺为:将牡蛎散饮片浸泡40 min后用煎药机在110℃的条件下煎煮30 min.本试验可为规范化煎煮中药汤剂提供一定的理论依据及试验数据.

A 43-year-old female patient received Fuyanshu capsules 1.6 g orally thrice daily for pelvic inflammation. The traditional Chinese medicine decoction was added 1 week later. After 10 days of combination therapy, the patient developed fatigue, which was gradually aggravated, and yellowish skin and sclera appeared. Seven days later, laboratory tests showed alanine aminotransferase (ALT) >1 000 U/L, aspartate aminotransferase (AST) >750 U/L, gamma-glutamyltransferase (γ-GT) 148 U/L, alkaline phosphatase (ALP) 153 U/L, and total bilirubin (TBil) 56.3 μmol//L. After excluding viral hepatitis, autoimmune liver disease, obstructive jaundice, and other causes, liver injury caused by Fuyanshu capsules combined with traditional Chinese medicine decoction was considered. After Fuyanshu capsules and traditional Chinese medicine decoction were discontinued, reduced glutathione, glycyrrhizic acid preparation, and ursodeoxycholic acid were given. Seven days later, the patient′s symptoms were improved obviously and laboratory tests showed ALT 323 U/L, AST 125 U/L, γ-GT 149 U/L, ALP 109 U/L, and TBil 35.8 μmol/L. Twenty-seven days later, the patient′s symptoms disappeared and laboratory tests showed ALT 62 U/L, AST 42 U/L, γ-GT 67 U/L, ALP 67 U/L, and TBil 18.7 μmol/L. There are 7 same components in Fuyanshu capsule and traditional Chinese medicine decoction. It was considered that the liver injury was related to the increase of hepatotoxicity caused by the combination of the two drugs.

目的 优化茵陈蒿汤煎煮工艺.方法 以浸泡时间、加水量、煎煮时间为影响因素,绿原酸、咖啡酸、新绿原酸、异绿原酸B、栀子苷、大黄素、芦荟大黄素、大黄酚、大黄酸、大黄素甲醚溶出率和出膏率的综合评分为评价指标,正交试验结合信息熵理论优化煎煮工艺.结果 最佳条件为饮片加18倍量水浸泡50 min后煎煮2次,每次30 min,综合评分为33.33分.结论 该方法稳定可行,重复性高,可用于煎煮茵陈蒿汤.

目的 建立五味消毒饮(金银花、蒲公英、野菊花等)HPLC指纹图谱,并同时测定新绿原酸、绿原酸、隐绿原酸、秦皮乙素、咖啡酸、木犀草苷、异绿原酸B、3,5-二咖啡酰奎宁酸、4,5-二咖啡酰奎宁酸、蒙花苷的含量.方法 该药物甲醇提取液的分析采用ZORBAX Eclipse XDB-C18色谱柱(4.6mmx250 mm,5 μm);流动相乙腈-0.1％磷酸,梯度洗脱;体积流量1.0mL/min;柱温25℃;检测波长320 nm.结果 10批样品指纹图谱中有34个共有峰,相似度均大于0.970.10种成分在各自范围内线性关系良好(r≥0.999 8),平均加样回收率95.16％～104.50％,RSD 1.09％～4.90％.结论 该方法准确可靠,重复性好,可用于五味消毒饮的质量控制.

目的:分析肿瘤患者伴有肝功能异常的临床保肝辅助用药的合理性.方法:选取医院2017年1月-2019年12月间肿瘤内科收治的被诊断为肿瘤,且抗肿瘤药物致肝功能异常的住院患者197例临床资料,统计其患者性别、年龄和吸烟饮酒史、肝脏基础疾病、肝功能生化指标、临床表现、保肝药物的使用情况与费用以及预后等信息,分析其保肝药物使用的合理性.结果:197例被诊断为肝功能异常的肿瘤患者中,其中既往有肝病史患者占40.61％、药物不良反应史患者占12.18％和饮酒史患者占32.49％;药物性肝损伤与肝脏基础疾病的肿瘤患者是引起肝功能异常的主要因素;出现肝功能异常(Ⅰ级或Ⅱ级)时,单用1种保肝药物的预后效果为最佳;出现Ⅲ级或Ⅳ级时,2种或3种保肝药物联合使用,预后效果为最佳;点评结果发现部分医嘱中保肝药物存在重复用药、适应证不适宜、联合用药不适宜、禁忌证及用法用量不合理.结论:肿瘤患者抗肿瘤药物致肝功能异常,应合理选用保肝药物辅助治疗,并针对其病情和肝损伤类型合理使用保肝药物,联合用药不宜超过3种.

目的 优选以根茎果实类饮片为主的当归建中汤的加水量参数.方法 采用HPLC法检测饮片及煎液中芍药苷、阿魏酸、甘草苷、甘草酸、桂皮醛的含量及浸出物含量,通过单因素考察和正交试验设计来优选当归建中汤的加水量参数.结果 煎煮当归建中汤的最佳加水量参数为加8倍量水,煎煮2次(第二煎水量与一煎相同).结论 优选出的工艺参数稳定可行,为按饮片类型分类规范处方的加水量标准提供了实验依据.

目的:分析医院3年间中药注射剂的临床使用情况及其合理性,为临床合理用药提供参考.方法:抽取2016年-2018年3年间中药注射剂临床使用品种、用药金额、用药频度(DDDs)、日均用药金额(DDC)等资料,分析其用药规律和临床用药的合理性.结果:3年间医院中药注射剂的用药金额逐年下降,这与中药注射剂价格调整有关;其中排名前3位的主要是抗癌药物、理血剂和肿瘤辅助药物,清热剂和开窍剂的DDDs排名较靠前;醒脑静注射液和热毒宁注射液DDDs连续3年名列榜首.结论:中药注射剂静脉药物的不合理用药现象得到显著改善,不合理医嘱发生率逐年下降,有效遏制了中药注射剂不合理用药事件的发生.

目的 分析我院肿瘤内科住院患者发生药物性肝损伤的情况,总结肝损伤的临床表现,评价药物因果关系.方法 回顾性追踪2014年1月～2018年12月在我院肿瘤内科住院期间发生药物性肝损伤的患者信息,运用RUCAM评分表进行药物性肝损伤因果关系的评价.结果 我院肿瘤内科共有130名患者发生药物性肝损伤,男性72名,女性58名,平均年龄为(64.4±10.71)岁,肝损伤的主要临床表现为乏力、皮肤黏膜黄染、腹部疼痛、纳差等.64例患者为胆汁淤积型,20例为肝细胞损伤型,46例为混合型,化疗药物引起肝损伤出现频次最高的是替吉奥、阿帕替尼、卡培他滨、奥沙利铂、顺铂等.结论 化疗药物引起的药物性肝损伤是导致肿瘤内科患者病情变化的重要原因之一,医务人员在医疗监护过程中应加强对药物性肝损伤的重视.