胰源性门静脉高压(PSPH)是由脾静脉(SV)流通受阻引起的一种临床综合征,在临床较为罕见且对患者造成生命威胁,但却为门静脉高压唯一可治愈的类型。其主要发病诱因是胰腺原发疾病,通常为胰腺急(慢)性炎症、胰腺占位性病变和胰腺手术操作导致。1型孤立性食管胃底静脉曲张、脾大、脾功能亢进是PSPH的主要临床表现特征,其中食管胃底曲张静脉破裂出血是PSPH最为严重的并发症;患者若表现为肝功能正常但出现原因不明脾肿大并伴有消化道出血症状,应考虑可能出现了PSPH。PSPH的治疗可分为胰腺原发病、门静脉高压及并发症的综合性诊治。本文旨在回顾PSPH的相关文献,对其有关临床诊断与治疗现状进行综述,以期指导医务工作者在临床中尽早发现PSPH并对患者及时有效治疗。
Pancreatic segmental portal hypertension(PSPH)is a clinical syndrome caused by spleen vein(SV)occlusion or stenosis.It is a rare and life-threatening hemorrhagic disease of the upper digestive tract,but it is the only curable type of portal hypertension.The main cause is primary pancreatic disease,which is usually due to acute or chronic pancreatic inflammation,pancreatic space-occupying lesions and pancreatic surgery.Type 1 isolated esophagogastric varices,splenomegaly and hypersplenism are the main clinical features of PSPH,and esophagogastric variceal bleeding is the most serious complication of PSPH.PSPH should be considered in patients with normal liver function but unexplained splenomegaly accompanied by gastrointestinal bleeding.The treatment of PSPH can be divided into a comprehensive diagnosis and treatment of primary pancreatic disease,portal hypertension and complications.Therefore,the purpose of this paper is to review relevant literature of PSPH,the relevant clinical diagnosis and treatment status quo were summerized,in order to guide the medical workers in clinical PSPH,early detection and timely and effective treatment for patients.
目的 采用网络药理学方法与分子对接技术分析白头翁汤治疗细菌性痢疾(BD)的潜在活性成分与作用机制。方法 借助中药系统药理学数据库与分析平台(TCMSP)及PubChem数据库检索筛选白头翁汤方的化学成分和作用靶点,通过Uniprot数据库校正基因名,同时通过比较毒物基因组学数据库(CTD)、药物靶标数据库(TTD)、GeneCards数据库和药物和药物靶标数据库(DRUGBANK)获得BD相关疾病靶点。经在线绘图平台微生信分析“活性成分-疾病”交集靶点,使用Cyoscape 3.7.2软件构建可视化的中药-活性成分-靶点网络、蛋白质互作网络,筛选潜在的关键活性成分与核心靶点;通过Metascape数据库对进行靶点的基因本体(GO)功能分析和京都百科全书基因和基因组通路数据库(KEGG)通路富集分析,同时使用Cyoscape 3.7.2软件构建基因-通路网络,筛选潜在的通路及其作用机制。同时采用分子对接技术对白头翁汤中关键活性成分和BD核心靶点进行分析。结果 白头翁汤共筛选出266个潜在活性成分,其中,槲皮素、β-谷甾醇、异鼠李素、异延胡索单酚碱、小檗红碱、豆甾醇等66个关键活性成分可通过肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、前列腺素内过氧化物合酶2(PTGS2)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、血管内皮生长因子A(VEGFA)、V-rel网状内皮细胞病毒癌基因同源物A(RELA)、半胱氨酸天冬氨酸蛋白酶3(CASP3)、白细胞介素-8(CXCL8)、白细胞介素-1B(IL-1B)、丝裂原活化蛋白激酶1(MAPK1)、白细胞介素-10(IL-10)等33个潜在交集靶点作用于BD。GO基因功能分析共得到生物过程(BP)条目20个、细胞组成(CC)条目6个、分子功能(MF)条目9个(P<0.01),主要涉及外部凋亡过程、细胞迁移正向调控、细胞因子受体结合、蛋白同源二聚活性、TNF受体超家族结合等生物进程。KEGG通路富集分析确定13条信号通路(P<0.01),主要涉及癌症信号通路、白细胞介素-17(IL-17)信号通路等关键通路。分子对接结果显示槲皮素、β-谷甾醇、异鼠李素、异延胡索单酚碱等核心活性成分与TNF、IL-6、PTGS2核心靶点具有良好的结合效应(结合能<-5 kJ/mol)。结论 白头翁汤主要通过槲皮素、β-谷甾醇等潜在的多种活性成分作用于TNF、IL-6、IL-1B、PTGS2、AKT1、VEGFA等潜在的关键靶点调控IL-17等信号通路,从而发挥治疗细菌性痢疾的作用,符合中药复方多成分、多靶标、多途径起效的显著特征。
Objective To analyze the potential active ingredients and mechanism of Baitouweng Decoction in the treatment of bacillary dysentery(BD)by means of network pharmacology and molecular docking technology.Methods With the help of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(Traditional Chinese Medicine Systems Pharmacology Database,TCMSP)and PubChem database to search and screen the chemical composition and target of Baitouweng Decoction,the gene name was corrected through the Uniprot database,and the CTD database,TTD database,GeneCards database and DRUGBANK database obtain BD-related disease targets.The intersection target was obtained through the online drawing platform,and Cytoscape 3.7.2 was used to construct a network of Pulsatilla active ingredient-component disease intersection target.The protein-protein interaction analysis of the intersection target was performed through the String database,and the Cytoscape 3.7.2 software was used for visualization.The Metascape database platform performed GO function analysis and KEGG pathway enrichment analysis on the target to predict its mechanism of action.The key active ingredient compounds in Baitouweng Decoction were molecularly docked with the core protein in the intersection target.Results A total of 266 potential active ingredients in Baitouweng Decoction were screened,of which 66 key active ingredients such as quercetin,β-sitosterol,isorhamnetin,Isocorypalmine,berberine,stigmasterol,etc.It acts on BD through 33 potential intersection targets such as TNF,IL-6,PTGS2,AKT1,VEGFA,RELA,CASP3,CXCL8,IL-1B,MAPK1,IL-10.GO gene function analysis yielded a total of 20 biological process(BP)entries,6 cell composition(CC)entries,and 9 molecular function(MF)entries(P<0.01),which mainly involve external apoptosis process and positive regulation of cell migration,Cytokine receptor binding,protein homodimerization activity,tumor necrosis factor receptor superfamily binding and other biological processes.KEGG pathway enrichment analysis identified 13 signal pathways(P<0.01),mainly related to key pathways such as cancer signal pathway and IL-17 signal pathway.The results of molecular docking showed that the core active ingredients such as quercetin,β-sitosterol,isorhamnetin,Isocorypalmine and TNF,IL-6,PTGS2 core targets have good binding effects(binding energy <-5 KJ /mol).Conclusions Baitouweng Decoction modulated signaling pathways involving IL-17 through its active constituents like quercetin and β-sitosterol,targeting key molecules such as TNF,IL-6,IL-1β,PTGS2,AKT1,and VEGFA,reflecting the multi-target therapeutic approach of traditional Chinese medicine.
目的 评价不同间变性淋巴瘤激酶(ALK)抑制剂联合安罗替尼治疗非小细胞肺癌(NSCLC)的疗效。方法 收集ALK突变阳性NSCLC患者的临床资料,筛选服用ALK抑制剂疗效不佳再加用安罗替尼的病例。根据不同的用药方案分为阿来替尼+安罗替尼,塞瑞替尼+安罗替尼和克唑替尼+安罗替尼三个组别。记录患者联合用药前最近一次的影像学检查结果,并以此为基线按Recist1.1评价疗效,以病情进展、患者死亡、停药、改变治疗方案为终点计算各组患者的无事件生存期(EFS),收集肿瘤标志物、血常规和肝功、心功能、肾功能生化检测等指标数据,统计分析患者联合用药前后各项指标的变化。结果 经筛选,共纳入49例患者的临床数据。阿来替尼+安罗替尼组有23例,疾病控制率(DCR)为86.96%;平均EFS为(10.8±3.6)个月,中位EFS为8.3个月;塞瑞替尼+安罗替尼组有14例,DCR为71.43%;平均EFS为(6.5±2.9)个月,中位EFS为5.6个月;克唑替尼+安罗替尼组有12列,DCR为66.67%;平均EFS为(7.7±3.2)个月,中位EFS为7.2个月。阿来替尼+安罗替尼组的平均EFS长于另外两组(P<0.05)。各研究组肿瘤标志物仅有CyFra21-1在克唑替尼+安罗替尼组在联合用药后升高(P<0.05),生化检测和血常规指标在用药前后差异无统计学意义(P>0.05)。结论 ALK抑制剂与安罗替尼联用,疗效最好为阿来替尼,其次为塞瑞替尼,最后为克唑替尼。三种ALK抑制剂与安罗替尼联用后,均未导致心、肝、肾功能和血细胞损害。
Objective To evaluate the efficacy of different anaplastic lymphoma kinase(ALK)inhibitors combined with anlotinib in the treatment of non-small cell lung cancer(NSCLC).Methods Clinical data of drug resistant NSCLC patients with ALK positive mutation was collected who were treated with ALK inhibitors and anlotinib synchronously.According to different regimens,three groups were set,alectinib+anlotinib,ceritinib+anlotinib,and crizotinib+anlotinib.The latest imageological examination results of the patient before the synchronous therapy was set as the baseline to evaluate the therapeutic effect according to Recist1.1.The event free survival(EFS)of each group was calculated with disease progression,patient death,treatment discontinuation and changing regimen as endpoints.Data of tumor markers,hematology test,liver function,cardiac function,renal function biochemical examination was collected and analyzed statistically before and after the combination therapy,with P<0.05 as the statistically significant difference.Results After screening,clinical data of 49 patients were collected.Twenty-three patients in the alectinib+anlotinib group,with a disease control rate(DCR) of 86.96%;mean EFS was(10.8±3.6)months,median EFS of 8.3 months;14 patients in the ceritinib+anlotinib group,with a DCR of 71.43%,mean EFS was(6.5±2.9)months,median EFS was 5.6 months;12 patients in the crizotinib+anlotinib group,with a DCR of 66.67%,mean EFS was(7.7±3.2)months,median EFS was 7.2 months.EFS of alectinib+anlotinib group was longer significantly than the other two groups(P<0.05).Only CyFra21-1,increased significantly after the combination of crizotinib and anlotinib(P<0.05).No statistically significant difference in biochemical test and hematology test before and after the treatment(P>0.05).Conclusions The therapeutic effect of ALK inhibitors with anlotinib was ordered,alectinib being the most effective,followed by ceritinib and finally crizotinib.The combination of ALK inhibitors with anlotinib did not cause any abnormal results in the examination of heart,liver,kidney and blood cells.
实体瘤对免疫治疗应答非常有限,因此,如何有效提升肿瘤免疫治疗的疗效,已成为当前肿瘤免疫治疗领域亟待解决的关键难题与挑战。髓系来源抑制性细胞(MDSCs)的趋化募集及其所介导的肿瘤免疫逃逸机制,是制约实体瘤免疫治疗效果的核心因素之一。文章深入探讨了MDSCs的起源、表型特征、其介导肿瘤免疫逃逸的具体机制,以及当前针对MDSCs的靶向治疗策略与将MDSCs靶向疗法与肿瘤免疫治疗相结合的最新研究进展。此外,文章还系统性地分析了靶向MDSCs联合免疫治疗策略所面临的关键挑战,并据此提出了MDSCs的精准靶向策略。这一策略旨在精确激活抗肿瘤免疫反应,为癌症患者提供更为个性化、高效的治疗方案,从而开启肿瘤免疫治疗领域的新纪元,为癌症治疗策略的创新与发展贡献力量。
Solid tumors exhibit a very limited response to immunotherapy.Consequently,effectively enhancing the therapeutic efficacy of tumor immunotherapy has emerged as a critical challenge and problem that urgently needs to be addressed in tumor immunotherapy.The chemotaxis and recruitment of myeloid-derived suppressor cells(MDSCs)and the tumor immune evasionmechanisms mediated by them are one of the core factors that significantly restrict the efficacy of immunotherapy for solid tumors.In this review,we discuss the origins and phenotypic characteristics of MDSCs,the specific mechanisms by which they mediate tumor immune evasion,as well as current targeted therapeuticstrategies for MDSCs and the latest research progress in combining MDSC-targeted therapy with tumor immunotherapy.Furthermore,we have systematically analyzed the key challenges faced by the combination of MDSC-targeted and immunotherapy strategies,and accordingly proposed a precise targeting strategyfor MDSCs.This strategy aims to precisely activate anti-tumor immune responses,providing more personalized and efficienttreatment options for cancer patients,thereby opening a new era in tumor immunotherapy and contributing to the innovation anddevelopment of cancer treatment strategies.
近年来浆细胞性乳腺炎的发病率逐渐升高,已占乳腺疾病的4%~5%,该病易反复发作,经久不愈,抗生素、糖皮质激素、抗结核药、他莫昔芬等治疗效果不明显,单纯手术切除如切除范围小极易复发,而切除范围大则乳腺外形变化较大,严重者甚至需要切除乳腺。乳腺外形的缺损改变对患者身心健康造成伤害。随着研究不断深入,采用中西医结合治疗浆细胞性乳腺炎,可取得较好的治疗效果,降低复发率,而且对乳腺外观无影响。该文通过对文献的整理,对中西医结合治疗浆细胞性乳腺炎进行论述。
In recent years,the incidence of plasma cell mastitis has gradually increased,accounting for 4 % ~ 5 % of breast diseases.The disease is prone to repeated attacks and unhealed for a long time.The treatment effect of antibiotics,glucocorticoids,anti-tuberculosis drugs and tamoxifen is not obvious.Simple surgical resection is easy to relapse if the resection range is small,while the shape of the breast changes greatly,if the resection range is large.And even the breast needs to be removed in severe cases.The defect change of breast shape is harmful to the physical and mental health of patients.With the deepening of research,the combination of traditional Chinese and Western medicine in the treatment of plasma cell mastitis can achieve better therapeutic effect,reduce the recurrence rate,and has no effect on the appearance of breast.This article discusses the treatment of plasma cell mastitis with integrated traditional Chinese and Western medicine by sorting out the literature.