Many people engagingin medical scienceasked me,"You’ve beenworking on the exploration of Holistic Integrated Medicine（HIM）for quite awhile.What is the progressyou have made in your research?Have you got your article published?May I beyour first reader?"
目的 从c-JUN调控的糖基化角度探究追毒方逆转三阴性乳腺癌(TNBC)耐药的机制.方法 MTT检测细胞增殖,采用Western blot检测c-JUN、β3GnT8和ppGalNAc-T1/2、CD147、耐药蛋白BCRP和MDR1的表达.采用转染c-JUN质粒建立过表达c-JUN的MDA-MB-231/ADR细胞.体内实验采用耐药TNBC原位移植裸鼠模型.结果 追毒方可显著抑制MDA-MB-231/ADR细胞的增殖(P<0.01),具有时效和量效关系;可明显抑制耐药TNBC原位移植裸鼠的肿瘤质量(P<0.01);降低耐药蛋白BCRP和MDR1表达(P<0.01),并同时明显降低c-JUN、β3GnT8和ppGalNAc-T1/2、CD147蛋白的表达(P<0.05).过表达c-JUN后,与空白质粒对照组比较,β3GnT8、ppGalNAc T1/2、CD147、BCRP和MDR1的表达均显示增加(P<0.05,P<0.01).而空白质粒对上述蛋白的表达无影响.追毒方可以显著降低过表达c-JUN后的上述蛋白的表达,但其表达水平还是显著高于空白质粒加药组(P<0.05,P<0.01).结论 追毒方通过作用于调控因子c-JUN,下调β3GnT8和ppGalNAc-T1/2的激活,从而抑制CD147的糖基化修饰,导致耐药蛋白BCRP和MDR1下调而逆转TNBC耐药.
OBJECTIVE To investigate the potential of glycyrrhizic acid(GL)to improve the solubility and bioavailability of ost-hole(Ost),and to explore the underlying mechanism of the potential solubility and pharmacokinetic interactions.METHODS Male Sprague-Dawley rats were orally given osthole(20 mg·kg-1)alone or with glycyrrhizic acid(45 mg·kg-1).Blood and liver samples were collected at specific time points and determined by an LC-MS/MS method.The effect of glycyrrhizic acid on the solubility of ost-hole,and physical characterizations,including X-ray diffraction(XRD)and Fourier transform infrared(FT-IR)spectroscopy,were performed to reveal the mechanism of the solubilization of GL.In addition,bidirectional transport study using Caco-2 cell monolayer model was employed to study the effects of glycyrrhizic acid and its active metabolite glycyrrhetinic acid(GC)on the absorption of ost-hole.In incubation studies,rat enterocyte S9 and liver S9 were used to explore the potential effect of GL and GC on the metabolism of osthole.RESULTS The results of pharmacokinetics in rats showed that co-administration of glycyrrhizic acid could significantly in-crease the AUC of osthole as compared with osthole administered alone.The results of rat liver tissue samples indicated that glycyrrhizic acid increased the distribution of osthol in liver tissue.Solubility study found that glycyrrhizic acid could significantly enhance the solu-bility of osthole in water due to the decreased crystallinity of osthole and the formation of hydrogen bonding between Ost and GL.Caco-2 cell monolayer model demonstrated that neither GL nor GC could enhance osthole absorption.Further in vitro incubation study re-vealed that there was little metabolic interaction between osthole and GL or GC in phaseⅠmetabolism.CONCLUSION Increased AUC and liver concentration of osthole are probably due to the increased solubility of osthole by GL.The current study has significant implications for further investigation on the potential combination use of natural solubilizing agent GL and drugs with solubility as the rate-limiting step to absorption from the gastrointestinal tract.
OBJECTIVE To identify Magnoliae Flos and its related species using DNA barcoding technology,so as to establish a rapid,accurate and convenient method for identification of Magnoliae Flos.METHODS Genomic DNA of 21 Magnoliae Flos and their related species were extracted,and ITS,ITS2,psb A-trn H,mat K and rbc L gene sequences were amplified and sequenced.MEGA7.0 software was used for sequence comparison,and the intraspecific and interspecific genetic distance was calculated based on Kimura-2-Parameter(K2P)model to evaluate Barcoding gap,and the NJ phylogenetic trees were constructed to react identification re-sults.RESULTS Among the 5 primers,psb A-trn H and mat K could normally amplify the target gene,and the success rate of them was higher than 98%,while the success rate of rbc L sequencing was 38.1%only.The mat K sequence had the highest number of varia-tion sites,and psb A-trn H had the most prominent species discriminatory on Barcoding gap analysis relative to mat K and rbc L.The NJ phylogenetic tree showed that psb A-trn H+mat K barcode sequence could accurately identify 9 varieties,and distinguish Magnoliae Flos and its relatives.In addition,we applied it to the molecular identification of Magnolia grafting rootstocks for the first time.CONCLU-SION The sequence combination of psb A-trn H+mat K can realize the accurate identification of Magnoliae Flos,and can be applied to the rapid identification of Magnolia grafting rootstocks.
Yigong powder is one of the classic famous prescriptions published in the Catalogue of Ancient Classical Famous Pre-scriptions(the Second Batch of Pediatrics).Through systematically collating textual research and analyzing ancient literatures and clini-cal literatures on Yigong decoction,the key issues of prescription origin,composition,drug base,processing method,usage and dos-age,efficacy and indications of Yigong powder were summarized,providing literature data support for the development and clinical ap-plication of the classic pediatric prescription of Yigong powder.According to the analysis and research,Yigong powder comes from Qian Yi's Key to Diagnosis and Treatment of Children's Diseases and is consisted of ginseng,poria cocos,atractylodes,tangerine peel and licorice,with ginger and jujube being used as guiding medicine.The medicinal base follows the 2020 edition of Chinese Pharmaco-poeia.Ginseng,poria cocos,and orange peel are used as raw products,atractylodes is used as bran fried atractylodes,licorice is used as processed licorice.Children should be differentiated from adults in terms of drug dosage.The dosage for children is 1.4—1.7 g each for ginseng,poria cocos,atractylodes,tangerine peel and licorice,and the dosage for adults is 5.6 g—6.8 g each.The method of making and taking medicine is to file drugs down,take 300 mL water,add ginger and jujube and fry to 210 mL,take warm medicine before meals and adjust the frequency according to the actual situation.The ancient prescription was often used in children anorexia,diarrhea and other diseases.After the innovation of later generations of doctors,it is also used for digestive system diseases,recurrent respiratory tract infections in children,allergic rhinitis and so on.
OBJECTIVE To observe the effect of Wenjing Tongluo Decoction on IL-1β-induced inflammation of articular chon-drocytes and explore its mechanism.METHODS Primary chondrocytes were extracted from knee cartilage of mice and identified by toluidine blue staining.The chondrocyte inflammation model was induced by IL-1β.Lentiviral RNAi-HMGB1 was transfected into chondrocytes to interfere the expression of HMGB1.Then the cells were intervened with different concentrations of Wenjing Tongluo Decoction containing serum.Western Blot was used to analyze the protein expression of HMGB1 and NF-κB signaling pathway.The ex-pression of HMGB1,NF-κB1,NF-κB2 mRNA was detected by qPCR.ELISA was applied to detect the expression of inflammatory fac-tors IL-6,PGE-2 and TNF-α in cell supernatants.RESULTS Compared with normal cultured cells,the expression of HMGB1 in-creased significantly(P<0.01)in the IL-1β-induced chondrocyte inflammatory model,and the relative expression of p-IκBα/IκBα and p-P65/P65 proteins and the expression of NF-κB1 and NF-κB2 mRNA were increased(P<0.01).Compared with the model group,lentiviral RNAi-HMGB1 transfection could significantly downregulate the expression of HMGB1(P<0.01),and inhibit the upregulation of the relative expression of p-IκBα/IκBα(P<0.01)and p-P65/P65 protein and NF-κB1 and NF-κB2 mRNA expression(P<0.05).Compared with the model group,different concentrations of Wenjing Tongluo Decoction showed inhibitory effects on HMGB1 and NF-κB signaling pathways,demonstrated by the decrease in the protein expression of HMGB1,p-IκBα/IκBα and p-P65/P65(P<0.05).CONCLUSION Wenjing Tongluo Decoction can improve IL-1β-induced chondrocyte inflammation,and its mechanism may be related to inhibition of HMGB1-mediated activation of NF-κB signaling pathway.
OBJECTIVE To observe the clinical efficacy of modified Chaihu Guizhi Decoction in treating stable angina pectoris with anxiety/depression in patients with coronary heart disease of qi stagnation and blood stasis type.METHODS 60 patients with stable angina pectoris and anxiety/depression caused by qi stagnation and blood stasis type of coronary heart disease were included in the study.They were randomly divided into a control group(n=30)and a treatment group(n=30).Both groups of patients received health education,psychological counseling,and routine treatment for coronary heart disease angina pectoris.The control group received droperidol melitracin tablets in addition to basic treatment,while the treatment group received modified Chaihu Guizhi Decoction in ad-dition to basic treatment for 4 weeks.The efficacy of traditional Chinese medicine(TCM)syndrome,total score of traditional Chinese medicine syndrome,angina symptom score,electrocardiogram treadmill exercise test,nitroglycerin withdrawal rate,self-rating anxiety scale(SAS),self-rating depression scale(SDS),and Seattle angina questionnaire(SAQ)scores between the two groups of patients were compared before and after treatment.At the same time,peripheral blood lipids and IL-6 levels were measured.RESULTS Af-ter treatment,the TCM syndrome score,angina symptom score,SAS,SDS score of both groups of patients decreased(P<0.01),and the scores of various dimensions of SAQ increased(P<0.01).The occurrence time of ST segment depression of 1mm in treadmill exer-cise test was prolonged,the occurrence time of angina was prolonged,and the recovery time of ST segment was shortened(P<0.01),and TC,TG,LDL-C,IL-6 were significantly reduced(P<0.05,P<0.01).Moreover,the treatment group was superior to the con-trol group in improving TCM syndrome scores,angina symptom scores,SAS,SDS scores,PL and TS scores in SAQ,apparent effective rate of TCM syndrome,nitroglycerin cessation rate,blood lipids(TC,LDL-C),and serum IL-6(P<0.05,P<0.01).CONCLU-SION Modified Chaihu Guizhi Decoction can significantly improve the clinical symptoms,anxiety and depression status of patients with stable angina pectoris and anxiety/depression of qi stagnation and blood stasis type of coronary heart disease,improve quality of life,reduce blood lipids and IL-6 levels.
This paper systematically expounds the research advance and theoretical connotation of the kidney generating the marrow and unblocking brain collaterals,and points out the relationship between the kidney,marrow and brain in terms of structure and func-tion.The article proposes that brain marrow insufficiency is the key to the onset of cognitive impairment.Kidney deficiency runs through cognitive impairment,and phlegm and blood stasis are important pathological factors.The treatment should mainly focus on tonifying the kidney.Through the kidney-tonifying method,the purposes of nourishing the brain and marrow,strengthening the brain and memory,and helping to eliminate phlegm and remove blood stasis are proposed.Representative prescriptions for tonifying kidney yang and kidney yin are proposed to provide ideas and methods for the clinical prevention and treatment of cognitive impairment and the expansion of its prescription and medication selection.
OBJECTIVE This study aims to elucidate the mechanism of action of Isoliquiritigenin(ILG)in the treatment of Dia-betic Encephalopathy(DE)based on network pharmacological analysis and in-vitro experiments.METHODS The potential targets of ILG were predicted using the HERB database and SwissTargetPrediction database.DE-associated disease targets were obtained from GeneCards,OMIM,and PharmGkb,and the intersecting targets between ILG and DE were identified using the Venny software.A PPI network was constructed using the STRING database,and core targets were screened out using Cytoscape software.GO function and KEGG pathway enrichment analyses were undertaken using R 4.0.3,followed by validation via molecular docking techniques and in vitro experiments.RESULTS 65 intersecting targets between ILG and DE were identified in this study.Topological analysis yielded eight core targets namely,EGFR,ESR1,PTGS2,PPARG,GSK3β,CDK2,PIK3R1,and F3.GO function and KEGG pathway en-richment analyses revealed that ILG antagonizes DE through several biological processes which impact numerous cellular components and molecular functions such as response to lipopolysaccharides,protein phosphorylation,protein kinase activity,and serine/threo-nine/tyrosine kinase activity.Pathways implicated included the PI3K-Akt signaling pathway,protein polysaccharide signaling pathway in cancer,and endocrine resistance pathway.The molecular docking results showed that all eight core targets had a good binding with ILG,especially with GSK3β,with a binding energy of-7.22 kcal·mol-1.In vitro experiments indicated that ILG could improve high glucose-induced cell damage and activate the PI3K/AKT/GSK3β signaling pathway.CONCLUSION ILG is likely to exert its effects on GSK3β to regulate the PI3K/AKT/GSK3β signaling pathway,thereby alleviating DE.
As one of the modern scientific achievements,system theory can better explain and integrate traditional Chinese medi-cine(TCM).The article is based on the idea of system theory and combines TCM gasification thinking to deeply analyze the connota-tion of TCM surgical support method.It is believed that support method is based on the relationship between good and evil,with the or-gans,meridians,qi and blood as the main body of the system,and aims to restore the body's adaptive regulation ability.It reflects the systematic scientific characteristics of hierarchical evolution,leap,and overall emergence.Taking the treatment of chronic subdural he-matoma with support method as an example,the possibility of applying support method thinking to other modern surgical diseases was further explored and validated.
OBJECTIVE To observe the efficacy of Xingnao Kaiqiao acupuncture combined with modified Shaoyao decoction in the treatment of post-stroke limb spasm.METHODS 70 patients with post-stroke limb spasticity who met the inclusion criteria were selected and divided into an observation group and a control group with 35 cases each using the random number table method.The con-trol group received routine rehabilitation training and modified Shaoyao decoction,while the observation group was treated with Xingnao Kaiqiao acupuncture on the basis of the treatment of the control group.The course of treatment was 8 weeks for both groups.The tradi-tional Chinese medicine(TCM)syndrome scores,clinical efficacy,clinical spasm index(CSI),simple Fugl-Meyer assessment(FMA),modified Barthel index(MBI)in the two groups of patients before and after treatment were observed.RESULTS After treat-ment,the TCM syndrome scores of both groups decreased significantly(P<0.05,P<0.01),and the observation group was better than the control group(P<0.05,P<0.01);the curative effect in the observation group was better than that in the control group(P<0.05);the FMA and MBI scores of both groups increased significantly(P<0.01),and the CSI score decreased significantly(P<0.05),the observation group was better than the control group(P<0.05,P<0.01).No obvious adverse reactions occurred in either group during the treatment period.CONCLUSION Xingnao Kaiqiao acupuncture combined with Jiawei Shaoyao decoction can improve the pa-tients'limb spasticity,limb activity function and clinical symptoms,and improve the patients'daily living ability.
Based on the completion of literature search and evaluation and the formation of literature summary,the"TCM Classifi-cation and Determination Standards for Children's Constitution(Formulation)"was developed through three rounds of expert question-naires,expert validation sessions,cross-sectional surveys,and public opinion solicitation.The standards propose the scope of applica-tion,normative references,terms and definitions,age stratification,classifications of children's constitution,characteristics of chil-dren's constitution,and the determination of children's constitution of TCM.The purpose of this standard is to provide a standardized and objective reference for the clinical practice.
As a malignant tumor with high incidence and mortality worldwide,lung cancer seriously threatens the life and health of human beings.At present,clinical treatment of lung cancer is mainly based on surgery combined with radiotherapy and chemotherapy and other comprehensive treatments,which can control the progression of lung cancer to a certain extent,but there are still problems such as low survival rate and poor quality of life.Autophagy is a complex intracellular self degradation mechanism.The occurrence of autophagy is closely related to autophagy-related gene proteins and signal pathways.Research shows that reasonable regulation of signal pathway can interfere with autophagy leading to lung cancer cell death and inhibit tumor growth.In recent years,the regulation of auto-phagy-related signaling pathways in Chinese medicine against lung cancer has become a hot spot in the field of oncology research.Therefore,this paper compares and summarizes the research on the regulation of autophagy-related signaling pathways in Chinese medicine against lung cancer in recent years,in order to provide a reference basis for the development of new drugs and clini-cal application of Chinese medicine against lung cancer.
OBJECTIVE To evaluate the effect and mechanism of Qili Huanshao Formula(QLHSF)in ameliorating sex hormone disturbance and oxidative damage in testicular tissues of D-galactose-induced subacute aging mice.METHODS 105 male mice were randomly divided into the normal group,model group,low,medium and high doses of QLHSF group,vitamin E(VE)group and Jin Gui Shen Qi Wan(JGSQW)group.The subacute senescence model was established by continuous intraperitoneal injection of D-galac-tose(D-gal)and treated by intragastric administration,as well.The testicular histopathological damage was detected by HE staining.The levels of relevant sex hormones in serum were detected by ELISA.The expression of oxidative stress factors was detected by related kits.The apoptotic cells in testicular tissue were detected by TUNEL assay,and the expressions of oxidative stress and apop-totic related proteins in the testicular tissues of mice were detected by Western blot.RESULTS Compared to the aging model mice,all dose groups of QLHSF could obviously improve testicular tissue pathological damage.The levels of T,E2 and GnRH levels were in-creased,while LH and FSH were decreased in serum(P<0.01).Meanwhile,the SOD activity(P<0.01)and the levels of GSH(P<0.01)were increased,while MDA levels(P<0.01)were decreased in serum and testicular tissues.The medium dose group of QLHSF significantly inhibited testicular cell apoptosis(P<0.01),increased the expression of Nrf2,HO-1 protein and Bcl-2/Bax ratio(P<0.05),and down-regulated the expressions of Cleaved-Caspase-3/Caspase-3,Cleaved-Caspase-9/Caspase-9 apoptotic protein in the testis of mice(P<0.05).CONCLUSION QLHSF can effectively improve sex hormone disturbance and protect testicular tissue in aging mice,and the mechanism of action might be related to the inhibition of oxidative stress-induced apoptosis in testicular tissues.The study will provide reference and lay the foundation for the clinical application and functional anti-aging product develop-ment of Lycium barbarum and its formulations.
目的 探究参麦地黄汤联合缬沙坦对糖尿病肾病患者氧化应激、血管内皮功能及血清miR-133b、miR-135b的影响.方法 选取 2017 年 1 月至 2020 年 10 月于江阴市中医院门诊就诊的 90 例糖尿病肾病患者为研究对象,依据随机数字表法将其分为对照组、观察组各 45 例.对照组采用缬沙坦分散片口服治疗,观察组在对照组治疗基础上加服参麦地黄汤.2 组疗程均为3 个月,治疗前后评估2 组患者中医证候积分变化,检测2 组患者空腹血糖(FPG)和血清肌酐(SCr)、尿素氮(BUN)、尿微量白蛋白/肌酐比值(UACR)、氧化应激指标[超氧化物歧化酶(SOD)及丙二醛(MDA)]、血管内皮功能指标[可溶性细胞间黏附分子-1(sICAM-1)及内皮素-1(ET-1)]及miR-133b、miR-135b变化.结果 治疗后,2 组患者中医症候积分、FPG、SCr、BUN、UACR及MDA、sICAM-1、ET-1、miR-133b、miR-135b表达水平均显著下降,SOD活性明显升高(P<0.01),观察组优于对照组(P<0.01).观察组治疗总有效率高于对照组(P<0.01).结论 参麦地黄汤联合缬沙坦可有效改善糖尿病肾病临床症状,可能与其调控机体氧化应激、血管内皮功能、血清miR-133b、miR-135b水平有关.
总结黄春林教授以"五脏相关"理论辨治IgA肾病经验,认为IgA肾病的病位虽主要在肾与膀胱,但与肺、脾、心、肝等脏密切相关.病因可归纳为外感和内伤两方面,其中外感多因风、热、湿等邪毒侵袭人体;内伤多责之于脏腑功能的失调.病机核心在于肾气不固,肾中阴阳失调,气机升降失常,易外感内生病邪,标实邪气循经累及肾络,导致固摄无权,精血外溢,引发IgA肾病.治疗应从"以肾为本、五脏相关"的整体观出发,结合影响IgA肾病的发病、进展、难治因素及并发症进行辨证论治.
目的 运用网络药理学研究方法筛选散风通窍滴丸(SFTQ)活性成分,探讨其治疗过敏性鼻炎(Allergic rhinitis,AR)的靶点和作用机制.方法 利用中药系统药理学分析平台(TCMSP)筛选SFTQ的活性成分和作用靶点.运用TCMSP和TTD数据库筛选AR相关治疗靶点.通过Cytoscape构建SFTQ活性成分-AR疾病靶点网络,预测潜在靶点.采用Davidv 6.8 数据库对核心靶点进行KEGG通路富集分析.建立AR小鼠模型,用不同剂量的SFTQ进行激发期干预,通过行为学、病理切片HE染色、外周血EOS、IgE水平及颈部淋巴结中 ILC2 数量等指标进行评价.结果 筛选出 42 个活性成分,16 个潜在靶点.KEGG富集分析得到 18 条潜在信号通路,主要涉及T细胞受体信号通路、HIF-1 信号通路等.体内实验表明,SFTQ能显著减少AR小鼠喷嚏和挠鼻次数,减轻黏膜增厚程度,减少外周血中EOS,降低血清中IgE水平,同时能显著减少颈部淋巴结中ILC2 的数量.结论 运用系统药理学方法,揭示了SFTQ治疗AR的多成分、多靶点、多通路的特点,为SFTQ的机制研究提供了可能的靶点和有效成分,为更全面地认识及应用该方奠定了基础.
分析了经方理论与图论的相关性,提出基于图论的经方人工智能(AI)研究路径,从逻辑推理和命题逻辑角度分析图论与经方理论、思维的相关性,提出可行的研究路径.图论的应用能解决经方智能化研究中的知识表示问题,图的属性和度量方法有助于从中医思维出发进行知识发现,图的矩阵表示和图连通性能为经方智能辅助诊疗模型融入领域知识,提升模型效率.图论可为经方AI研究提供理论指导,基于图论的知识图谱等研究技术可为经方AI研究中的难题提供解决方案.
目的 针对名老中医治疗肺癌医案用药知识库构建任务,实现知识库的自动化补全.方法 设计名老中医治疗肺癌用药知识补全方法,对症状、诊断、中药、舌象和脉象之间的相关性进行分析,并根据阈值进行划分,在组成初始知识库的基础上使用CrossE知识表示模型结合负采样技术学习知识库中各实体和关系在向量空间中的嵌入表示,通过链路预测任务挖掘知识库中的隐藏关系.结果 在对医案中各实体进行皮尔逊相关性分析的基础上利用CrossE模型所预测的关系在Hit@1、Hit@3、Hit@5 和Hit@10 指标上分别达到了 16.19%、29.12%、35.85%和 47.60%,在 MeanRank指标上达到了 13.19.相较TransE、TransR等模型,有显著提升.结论 使用知识补全技术结合中医临床实践可以深入挖掘名老中医治疗肺癌的隐藏知识.
中医诊疗智能化是中医现代化发展的重要方向.大语言模型技术推动了人工智能发展,将其与中医药结合,构建大语言模型驱动的中医智能诊疗方法和应用,对中医创新发展具有重要意义.在分析和总结中医智能诊疗面临的挑战基础上,提出构建涵盖语料准备、知识表征、指令微调和强化学习于一体,大语言模型驱动的中医智能诊疗研究思路与方法,以期为中医诊疗的智能化研究提供参考.
