Screening and immune infiltration analysis of ferroptosis-related genes in pancreatic cancer with predictions for traditional Chinese medicine treatments

Background:This study aims to explore the involvement of ferroptosis-related genes and pathogenesis in pancreatic cancer and predict potential therapeutic interventions using Traditional Chinese Medicine(TCM).Methods:We utilized gene expression datasets,ferroptosis upregulated genes and applied machine learning algorithms,including LASSO and SVM-RFE,to identify key ferroptosis-related genes in pancreatic cancer.Perform Gene Ontology,Kyoto Encyclopedia of Genes and Genomes,and Disease Ontology enrichment analysis,immune infiltration analysis and correlation analysis between immune infiltrating cells and characteristic genes on differentially expressed genes using the R software package.Retrieve potential traditional Chinese medicine for targeted ferroptosis gene therapy for pancreatic cancer through Coremine and Herb databases.Results:Seventeen feature genes were identified,with significant implications for immune cell infiltration in pancreatic cancer.The results of immune cell infiltration analysis showed that B cells naive,B cells memory,T cells regulatory,and M0 macrophages were significantly upregulated in pancreatic cancer patients;Mast cells resting were significantly downregulated.Chinese herbal medicines such as ginkgo,turmeric,ginseng,Codonopsis pilosula,Zedoary turmeric,deer tendons,senna leaves,Guanmu Tong,Huangqi,and Banzhilian are potential drugs for targeted ferroptosis gene therapy for pancreatic cancer.Conclusion:TIMP1 emerged as a key gene,with several TCM herbs predicted to modulate its expression,offering new avenues for treatment.

Guideline for the diagnosis and treatment of rheumatoid arthritis with integrated traditional Chinese medicine and Western medicine to increase efficiency and reduce toxicity

Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We established a guideline working group consists of a steering committee,a secretary group,an evidence evaluation group,a consensus group and a review group and developed a guideline following the guidance of the World Health Organization Handbook and the Chinese Medical Association.The guideline includes 35 recommendations which reached consensus by the two rounds Delphi surveys.These recommendations were formulated to address the following themes of most concern to clinician:diagnostic imaging,disease staging,traditional Chinese medicine syndromes,effectiveness and toxicity of integrated traditional Chinese medicine and Western medicine.

Reflections on the Toxicity and Safety of Traditional Chinese Medicine Combined with the Cases of Nephrotoxicity and Hepatotoxicity

This paper analyzes the relationship between toxicity and safety of traditional Chinese medicine(TCM)based on the cases of current nephrotoxicity and hepatotoxicity,and summarizes the literature on hepatotoxicity and nephrotoxicity.It is found that the main reasons for the toxic reaction of TCM are own factors of drugs,irregular administration of medicine and individual difference.However,as long as the"quality"and"quantity"of TCM are guaranteed,the toxicity of TCM can be controlled within the safety range.

A Brief Discussion on the Toxicity of Traditional Chinese Medicine

With the wide application of traditional Chinese medicine in the world,the related reports on the toxicity of traditional Chinese medicine are increasing,which makes the safety of traditional Chinese medicine receive wide attention.This paper analyzes the toxicity of traditional Chinese medicine with a fair and scientific attitude,in order to promote the benign and sustainable development of traditional Chinese medicine.

Metabolomics and its application in the evaluation of toxicity of traditional Chinese medicine

Metabolomics is a newly developed discipline following genomics,transcriptomics,and proteomics.It is based on the theory of systems biology,supported by modern spectroscopy analysis technology and is analyzed by the external stimulation of organisms.By analyzing the overall changes of metabolites with low molecular weight in organism after being stimulated by the outside world,we can understand the physiological and pathological state of organism,and finally clarify the essence of biological changes of organism.In recent years,metabolomics has developed rapidly.It has been widely used in early toxicity screening of lead compounds,preclinical toxicity of drugs and toxicity evaluation of clinical drugs.The in-depth interpretation of metabolomics results is also developing.This article reviewed the progress of metabolomics technology and its application in the study of toxicity evaluation of traditional Chinese medicine.

Advances in Research of Toxic Traditional Chinese Medicines in the Treatment of Malignant Tumors

Combating poison with poison is an important method of traditional Chinese medicine to treat malignant tumors.This study reviews the experimental research on anti-tumor effects of toxic traditional Chinese medicines in recent years.It summarizes the action mechanism of toxic traditional Chinese medicines for the treatment of malignant tumors,including:inhibiting tumor cell proliferation and angiogenesis,inducing tumor cell apoptosis and differentiation,reversing tumor cell multidrug resistance(MDR),inhibiting tumor cell invasion and metastasis,and enhancing the body's immune functions.Finally,it discusses the research and development prospects of toxic traditional Chinese medicines as new anti-tumor drugs.

Application of LC-MS based glutathione-trapped reactive metabolites in the discovery of toxicity of traditional Chinese medicine

We summarized the discovery of liquid chromatography mass spectrometry （LC-MS） based glutathione （GSH） capture of reactive metabolites in traditional Chinese medicine （TCM）, which provides scientific basis for further research and clinical application of Chinese medicine toxicity discovery. This dissertation overviews relevant literatures of GSH capture of reactive metabolites in recent years. And then we review the principles and methods of LC-MS based GSH capture of reactive metabolites, as well as the research progress in the discovery of toxicity of TCM including pyrrolizidine alkaloids, furans and quinoid species. The review shows that the representative compounds of TCM includes adonifoline, lasiocarpine, diosbulbin B and safrol are well dctected by LC-MS based GSH capture technique. And the main analytic systems of LC-MS are triple quadrupole and Q-Trap mass spectrometer. Constant neutral loss scan （CNLS）, precursor ion scan （PIS） and multiple reaction monitor （MRM） are main detection methods to monitor the characteristic GSH conjugate fragmentations. The approach of LC-MS based GSH-trapped metabolites has a good application prospect in the discovery of toxic components of TCM.

A systematic review of treating Helicobacter pylori infection with Traditional Chinese Medicine

AIM: To evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of Helicobacter pylori (H pylori) infection. METHODS: We electronically and manually searched electronic databases, references lists and conferences compilations, and included all randomized clinical trials comparing the treatment of H pylori using TCM with proton pump inhibitor or colloidal bismuth subcitratebased triple therapy as controls. The Jadad score was used to assess trial quality, H pylori eradication rate and the incidence of side effects were taken as outcome measurements, and heterogeneity analysis, meta-analysis and funnel plot analysis were conducted. RESULTS: Sixteen trials were included. The Jadad scores of all the trials were not more than 2. Clinical heterogeneity and substantial statistical heterogeneity existed among the trials (P = 0.001, I 2 = 59%) and meta-analysis was not conducted. The average eradication rates following TCM and triple therapy were 72% and 78% and the incidence of side effects were 2% and 29%, respectively. The funnel plot was obviously asymmetric. CONCLUSION: Available evidence is not convincing enough to show that TCM has the same efficacy as triple therapy in H pylori treatment. TCM may be safer than triple therapy. TCM should not be recommended as monotherapy in H pylori infection.

Safety Research in Traditional Chinese Medicine: Methods, Applications, and Outlook

Traditional Chinese medicine (TCM) is a medical system that has collected and summarized abundant clinical experience over its long history of more than 2000 years. However, the frequent occurrence of TCM-induced adverse reactions has hindered the modernization and internationalization of TCM, while attracting increasing attention from around the world. Unlike chemical drugs and biological agents, the difficulties involved in research on the toxicity and safety of TCM mainly include the complexity of its components and the unpredictability of drug–body interactions. Much of TCM, which has overall therapeutic effects, has the typical mechanisms of multiple components, multiple pathways, and multiple targets. While considering the gradualness and unpredictability of TCM toxicity, the ambiguity of toxicants and safe dosage, and individual differences during long-term TCM administration, we have systematically established key techniques for the toxicity assessment of TCM. These techniques mainly include TCM toxicity discovery in an early phase, based on a combination of drug toxicology genomics and metabolomics;methods to identify dose–toxicity relationships in TCM;and integrated techniques for the exploration of TCM interactions, such as fast-screening tests based on drug-metabolizing enzymes and receptor pathways. In particular, we have developed a new technical system for TCM safety evaluation using molecular toxicology, which has been validated well in research on TCM compatibility contraindication, quality control, and allergen discovery. The application of this key technical platform is introduced here in detail. This application includes model organisms, toxicant biomarkers, a magnetic suspension technique, and the application of network toxicology and computational toxicology in research on the toxicity of Fructus toosendan, Semen cassiae, Polygonum multiflorum, and Fructus psoraleae.

飞龙掌血茎和根不同炮制品对小鼠的急性毒性试验

旨在了解飞龙掌血[Toddalia asiatica(Linn)Lam.]茎和根不同炮制对小鼠急性毒性作用。130只KM小鼠适应性喂养3 d后,随机分为13组,包括溶媒组和12个药物试验剂量组(1个药材茎生品组和5个茎炮制组,1个根生品组和5个根炮制组,其中5种药材炮制品包括水煮制品、水洗制品、水蒸制品、酒蒸制品和酒炙制品)。溶媒组小鼠按40 mL/kg给予纯净水灌胃,给药3次,间隔4~5 h;茎各炮制品试验组小鼠按40 mL/kg灌胃,给药3次,间隔4~5 h;根各炮制品试验组小鼠按30 mL/kg灌胃,给药2次,间隔4~5 h,记录给药后各组小鼠14 d的主要临床症状、体重变化,并统计死亡率。结果表明,飞龙掌血及各炮制品可对小鼠产生急性毒性作用,临床中毒症状有自主活动减少、安静怠动、俯卧和翻正反射消失。炮制品组与溶媒组比较,在14 d内茎和根各炮制品均可致小鼠体重明显降低,且死亡率显著高于溶媒组(P<0.05或P<0.01);而与生品组比较,茎和根的5种炮制品在14 d内对小鼠体重的影响不显著,可有效降低小鼠的死亡率,其中以水煮法效果最佳。水煮、水洗、水蒸、酒蒸、酒炙炮制方法可以减小飞龙掌血茎和根(生品)对小鼠的毒性作用,但对小鼠体脂影响不显著。

益气活血中药对化疗患者心脏功能的影响

目的探讨肿瘤治疗相关心血管毒性(CTR-CVT)的早期监测指标及益气活血类中药对CTR-CVT的预防作用。方法选取2019年1月至2022年1月该院行抗肿瘤治疗且经病理学诊断确诊的恶性肿瘤患者40例,将其按照1∶1比例随机分为对照组及治疗组,对照组接受化疗,治疗组在化疗基础上联合益气活血中药。比较2组心肌酶谱[α-羟丁酸脱氢酶(α-HBDH)、乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、谷草转氨酶(AST)]、B型脑钠肽(BNP)、肌钙蛋白Ⅰ(CTNⅠ)、左心室射血分数(LVEF)水平,并对心电图异常及心血管不良事件发生情况进行分析。结果对照组化疗后CK、CK-MB、α-HBDH、LDH、BNP水平高于化疗前,AST、CTNⅠ低于化疗前,差异无统计学意义(P>0.05)。治疗组化疗后α-HBDH、LDH、BNP、AST、CK、CK-MB、CTNⅠ水平与化疗前比较,差异无统计学意义(P>0.05)。2组化疗后BNP、α-HBDH、LDH水平比较,差异有统计学意义(P<0.05),但AST、CK-MB、CK、CTNⅠ水平比较,差异无统计学意义(P>0.05)。2组化疗后LVEF水平及心血管不良事件发生情况比较,差异有统计学意义(P<0.05)。2组化疗后心肌酶谱指标、BNP水平、CTNⅠ水平及心电图异常情况比较,差异无统计学意义(P>0.05)。结论心肌酶谱、BNP、CTNⅠ可以作为CTR-CVT的早期监测指标。益气活血类中药在一定程度上具有预防CTR-CVT的作用,其可以改善患者心脏功能及BNP、LVEF水平,降低心血管不良事件发生率。

Prediction of quality markers of traditional Chinese medicines based on network pharmacology

Network pharmacology is a powerful tool to reflect the pharmacologically active effects,mechanism of action and toxic activity of traditional Chinese medicines(TCMs).The ingredients of TCMs,associated with quality control of TCM products,are those fundamental chemicals that exhibit biological activities.A great amount of effort has been made by scientists in that field in order to improve the quality of TCMs,though the approaches to determine their quality and the TCM theory and compatibility rules remain ambiguous.Now some methods and technologies must be applied to predict and explore the quality marker(Q-marker)for quality control,as well as to clarify the factors affecting the quality of TCM,which may give new insight into rational ground of establishment of appropriate quality control and assessment system.In this review paper,authors focus on the prediction of quality markers of TCMs by network pharmacology based on three aspects:(1)from network medicine to network pharmacology,(2)complex network system of traditional Chinese medicine,and(3)predicting TCM quality markers based on network pharmacology.Authors proposed the research pattern on network pharmacology based on biological and medical networks,and further TCM network pharmacology based on substantial basis of TCM formulae,and the idea of"effect-ingredient-target-fingerprint"to predict and recognize the TCM Qmarker was the ultimate goal.In addition,authors yet noted how to make full use of the advantages of network toxicology to provide new ideas for the toxicity study of complex TCM systems and the prediction of TCM toxicity markers.

中老年冠心病心绞痛患者中医虚证诊断模型的探索与构建

目的 构建中老年冠心病心绞痛中医虚证的诊断预测模型。方法 选取2021年1月至2022年12月南京中医药大学泰州附属医院住院的160例冠心病心绞痛中老年(50~85岁)患者的临床资料,统计年龄、性别、体重指数、吸烟、饮酒、血常规、血脂、肝肾功能、冠状动脉血管病变程度,以及高血压病、糖尿病、胃肠道疾病、慢性阻塞性肺疾病、脑血管疾病等合并症作为自变量,每位患者均给出虚实辨证,其结果作为因变量。应用单因素logistic回归筛选变量,多因素logistic回归分析建立模型,可视化模型。使用受试者操作特征曲线、校准曲线及决策曲线分析评估模型。结果 160例患者实证83例,虚证77例。多因素回归结果显示:年龄>67~85岁[OR=2.776,95%CI(1.219,6.321),P=0.015]、糖尿病[OR=2.230,95%CI(0.960,5.178),P=0.062]、Genisi评分4.50~7.50[OR=10.126,95%CI(2.574,39.843),P=0.001]、Genisi评分8.00~15.75 [OR=13.510,95%CI(3.441,53.040),P<0.001]、Genisi评分16.00~80.00[OR=53.032,95%CI(11.769,230.027),P<0.001]是冠心病心绞痛虚证的预测因子。模型方程为:Logit(虚证概率)=-4.231+1.021×年龄(>67~85岁)+0.802×患糖尿病+2.315×Gensini等级(4.50~7.50)+2.603×Gensini等级(8.00~15.75)+3.952×Gensini等级(16.00~80.00)。该模型受试者曲线下面积值为0.852(95%CI:0.795~0.910)。校准度曲线提示准确度较好,决策曲线分析表现在该预测变量在6%~85%广大风险范围内展现出较好的正向收益率。结论 本研究构建了一个中老年冠心病心绞痛虚证诊断预测模型,有较好的临床预测能力。

中药增效减毒在肿瘤治疗中的研究概况

恶性肿瘤是人类死亡的主要原因之一,随着治疗水平的不断提升,如何应对治疗产生的不良反应,提高疗效成为新的研究方向。本文对近5年中药抗肿瘤增效减毒机制和临床应用研究进行综述,发现中药单体、复方、注射制剂被广泛应用于抗肿瘤的补充治疗,“扶正祛邪,固本清源”成为中医药治疗恶性肿瘤的治则,以活血化瘀、化痰降浊、清除癌毒等为主的方法可取得显著疗效,在增加肿瘤细胞杀伤力,逆转耐药性、调节肿瘤微环境等方面具有显著优势。

清火消痈汤治疗心肝火旺及热毒内蕴型肺痈临床观察

目的研究清火消痈汤治疗心肝火旺及热毒内蕴型肺痈的临床价值。方法以2021年1月—2021年12月为研究周期,抽取研究对象72例,采用随机数字表法分为研究组、对照组,各36例;对照组予西药治疗,研究组予清火消痈汤治疗,对比两组呼吸功能指标和中医证候积分。结果治疗后,研究组二氧化碳分压(PaCO_(2))水平为(41.42±3.75)mm Hg(1 mm Hg≈0.133 kPa),低于对照组的(47.59±5.88)mm Hg(P<0.05);氧分压(PaO_(2))水平为(82.99±6.75)mm Hg,高于对照组的(73.26±2.48)mm Hg(P<0.05)。治疗后,研究组主证积分为(2.44±0.68)分、次证积分为(0.65±0.11)分、总积分为(3.12±0.64)分,均低于对照组的(5.29±1.05)分、(1.89±0.62)分、(7.28±1.75)分(P<0.05)。结论清火消痈汤治疗肺痈效果显著。

泛凋亡因子在骨质疏松症中的诊断标记物及亚型分析

背景:研究推测泛凋亡可能参与了骨质疏松的病理过程,但目前尚未有泛凋亡基因在骨质疏松中的相关机制研究。目的:分析泛凋亡调节因子在骨质疏松症发生发展过程中的生物学机制。方法:从Gene Expresion omnibus(GEO)数据库中获得GSE56815数据集,提取泛凋亡基因进行差异分析。通过随机森林树模型筛选泛凋亡关键基因,构建疾病风险预测模型。运用共识聚类算法、单样本基因组富集分析以及免疫浸润分析探讨不同泛凋亡分子亚型间的差异性。通过医学本体信息检索平台Coremine medical数据库预测调节泛凋亡关键基因的中药药物。结果与结论:①基于4个泛凋亡关键基因(CASP1、CASP10、MEFV、TNF),确定了骨质疏松症中的诊断标志物,构建了患病风险预测模型并进行验证;②将骨质疏松患者分为2种不同的泛凋亡亚型(簇A、B和基因簇A、B),且簇B和基因簇B的泛凋亡评分分别高于簇A和基因簇A;③通过Coremine medical数据库预测出人参等能调节泛凋亡关键基因的中药药物。

宣肺败毒方治疗新冠病毒感染的中医学理论探讨及现代药理研究进展

目的探讨宣肺败毒方治疗新型冠状病毒感染的中医学理论,归纳该方的药理实验研究进展,为扩展该方的临床应用和进一步的实验研究提供参考。方法采用理论研究与文献调研相结合的方法,探讨宣肺败毒方的中医学理论和药理学进展,归纳该方的实验研究。结果宣肺败毒方适用于湿毒郁肺的患者,宣肺败毒方可通过PD-1/IL17A、IL-6/STAT3及CXCL2/CXCR2等通路改善肺损伤,以及NF-κB通路减轻肠道疾病。结论宣肺败毒方是中药和科技结合的产物,既有充分的中医药理论支撑,亦有足够的现代药理实验研究证据支持。

基于生物信息学研究宫内生长受限的免疫机制及中药预测

目的:基于生物信息学技术对宫内生长受限(IUGR)的芯片数据进行基因集富集分析(GSEA)以及关键差异基因的免疫浸润分析,并预测相关的作用中药。方法:从基因表达数据库(GEO)中获取GSE12216芯片数据,运用R软件筛选出差异表达基因(DEGs)。利用R包对数据集所有基因进行GSEA的基因本体论(GO)与京都基因与基因组百科全书(KEGG)分析以及DEGs的GO和KEGG分析;通过STRING数据库构建DEGs蛋白交互作用网络以及Cytohubba筛选关键基因;对关键基因进行ROC分析判断关键基因的诊断价值;通过单样本基因集富集分析(ssGSEA)算法获得24种免疫细胞在IUGR的含量及比例进行分析;通过Spearman统计方法计算关键基因表达与免疫细胞浸润的相关性,并利用Coremine数据库对免疫相关的关键基因进行中药预测。结果:共获得228个IUGR与正常胎盘的DEGs;GSEA结果显示IUGR样本的基因表达改变主要涉及趋化因子与受体以及溶酶体信号通路等过程;DEGs的GO和KEGG分析显示DEGs主要富集在肿瘤坏死因子(TNF)信号通路、缺氧诱导因子1(HIF-1)信号通路和Janus激酶/信号转导与转录激活子(JAK/STAT)信号通路;Cytohubba共筛选出10个关键基因:CSF2、IRAK1、PTGS2、FLT1、CHUK、CXCL12、FOS、LEP、CXCL2以及RELB;ROC分析显示这10个基因均有较高的诊断价值;免疫细胞的浸润矩阵分析结果表明,在IUGR胎盘组织中自然杀伤T细胞(NKT)以及单核细胞变化显著。免疫浸润与关键基因的相关性分析发现CSF2、IRAK1、PTGS2、CHUK、CXCL12、CXCL2以及RELB 7个基因与免疫浸润有相关性,中药预测发现,人参、黄芪与IUGR相关免疫浸润的关系最为密切。结论:NKT细胞与单核细胞在IUGR的发生发展中具有重要作用;共鉴定出7个与免疫浸润相关的关键基因;人参及黄芩可作为IUGR治疗的药物来源。

网络毒理学在中药研究中的应用现状与思考

网络毒理学是对中药多个“成分—靶点—通路”进行分析,从而预测毒性成分和探究毒性机制的方法.近年来,网络毒理学应用广泛,对其研究方法和应用现状进行综述,并对其面临的问题进行讨论,以期为网络毒理学在中药中的进一步应用提供参考.

多期组学特征联合应用在经中医药联合微创术综合治疗后肝癌早期复发中的预测价值

目的:探究基于多期CT影像组学特征联合应用在肝癌经中医药联合微创术综合治疗后早期复发的预测价值。方法:选取104例已确诊肝癌病例在接受综合治疗前一个月内的上腹部CT平扫及增强检查图像,用单因素和多因素Logistic分析筛选与肝癌早期复发相关的临床独立预测因素;使用ITK-snap软件对平扫期、动脉期、门静脉期图像进行病灶勾画,利用K最佳、LASSO对提取的组学特征进行筛选,使用LR、SVM、RF模型算法为筛选好的特征构建组学预测模型,通过AUC值、敏感度、特异度及ROC曲线等指标评估模型的预测效能,最后使在最优模型算法基础上具有稳健预测效能及高特异度的组学模型与临床独立预测因素结合构建综合预测模型。结果:通过Logistic分析发现肿瘤直径≥5 cm(P=0.05)、多发肿瘤(P=0.04)、门静脉栓塞(P=0.04)是与肝癌复发相关的临床独立预测因素;此外,在3种模型算法中SVM模型算法预测性能最好,并基于此模型算法构建的三期组学模型预测效能稳健(AUC值为0.96)且特异度最高(97%),使之与临床独立预测因素结合构建的综合模型AUC值为0.94,特异度为98.5%。结论:多期组学特征联合应用并与临床特征变量共同构建的综合模型可高效且准确地预测综合治疗肝癌病例的早期复发情况。