Luteolin, a flavonoid present in botanical drugs, plants, and dietary sources, has demonstrated anticancer properties against various tumors, yet its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to uncover the molecular mechanism of luteolin in DLBCL treatment using a combination of in vitro and in vivo experiments and computational analysis. Human DLBCL cell lines U2932 and OCI-LY10 were utilized to assess luteolin’s impact on cell growth, apoptosis, cell cycle progression, and the modulation of JAK2/STAT3 pathway proteins. In vivo, a U2932 tumor-bearing nude mice model was employed to evaluate luteolin’s antitumor efficacy and its effects on JAK2/STAT3 pathway protein expression. Additionally, molecular dynamics simulations were conducted to explore the interaction between luteolin and JAK2. The findings revealed that luteolin significantly suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase in both cell lines. In the mouse model, luteolin effectively inhibited tumor growth and downregulated the expression of phosphorylated JAK2 and STAT3 without altering the total protein levels of JAK2 and STAT3. Computational analysis indicated stable binding of luteolin to JAK2. Collectively, these results suggest that luteolin’s anti-DLBCL activity may be mediated through the regulation of the JAK2/STAT3 signaling pathway, positioning it as a potential therapeutic agent for DLBCL.

One of the major limitations of cancer therapy is the emergence of drug resistance. This review amis to provide a focused analysis of the multifactorial mechanisms underlying therapy resistance,with an emphasis on actionable insights for developing novel therapeutic strategies. It concisely outlines key factors contributing to therapy resistance, including drug delivery barriers, cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), cancer heterogeneity, tumor microenvironment (TME), genetic mutations, and alterlations in gene expression. Additionally, we explore how tumors evade targeted therapies through pathway-specific mechanisms that restore disrupted signaling pathways. The review critically evaluates innovative strategies designed to sensitize resistant tumor cells, such as targeted protein dedgradation, antibody-drug conjugates, structure-based drug design, allosteric drugs, multitarget drugs, nanomedicine and others We also highlight the importance of understanding the pharmacological actions of these agents and their integration into treatment regimens. By synthesizing current knowledge and identifying gaps in our understanding, this review aims to guide future research and improve patient outcomes in cancer therapy.

Background Lung cancer (LC) is the leading cause of cancer death in humans. tRNA-derived small RNA (tsRNA) is a novel biomarker that plays a crucial role in the genesis and development of LC. In this study, we aimed to investigate the value of differentially expressed tsRNA in LC through meta-analysis. Methods PubMed and Web of Science were searched until March 31, 2023. Diagnostic odds ratios (DORs) and area under the curves (AUCs) were used to evaluate the potential of tsRNAs as diagnostic markers for LC. Furthermore, hazard ratios (HRs) and 95% confidence intervals (95%CIs) were used to analyze the association of tsRNAs with LC prognosis. Results A total of 10 studies were included for analysis. Our results indicated that the combined DOR of total tsRNAs in LC diagnosis was 5.45, and AUC was 0.76. Subgroup analysis showed that high expression of tsRNAs in serum had higher diagnostic efficacy (DOR = 15.94, AUC = 0.87). Moreover, high expression of tsRNAs was associated with a worse prognosis in LC patients (HR = 1.59, 95%CI: 1.33–1.90). Conclusion Our findings suggest that high expression of tsRNAs has potential value in the diagnosis and prognosis of LC patients. However, further high-quality studies are needed to validate our results.

Occurrences of T-cell acute lymphoblastic leukemia (T-ALL) arise in approximately 10-15% of pediatric ALL cases and the outcomes for high-risk T-ALL are inferior. Currently, the precise dissection of clonal evolution with intra-tumoral heterogeneity and to delineate targetable molecular events driving relapse in T-ALL subtypes have become area of interest. We carried out high-throughput droplet-based 5′-single-cell RNA-sequencing (scRNA-seq) and paired T-cell receptor sequencing (scTCR-seq) of isolated CD7 + BMMCs from five patients' Dx_Rel paired samples. To investigate the gene signature variation underlying leukemic progression, we observed two distinct patterns of evolutionary trajectories in the four Dx_Rel nonETP-ALL pairs. From T956 and T723, a significant outgrowth in TCR initially negligible diagnostic subclusters at relapse, to which surrogate TCR repertoires were correspondingly linked and enumerated, suggestive robust dominant “clonal shifts” under continuous chemotherapeutic pressure. Whereas in Dx_Rel pairs T593 and T856, which contained subclusters with distinct gene signatures at diagnosis or relapse respectively, shared an identical TCR genotype (TCR Dx-Rel major clone). The clonal architecture clues gained from simultaneous scRNA-seq and scTCR-seq are strongly indicative of the leukemic “clonal drift” that commonly occurs under chemotherapeutic stress, during which somehow, hypothetically, molecular signatures within the same TCR subclones intrinsically progressed over time ( Fig. A-H). Next, we designed a targeted scDNA-seq library within a custom panel covering 127 amplicons and 102 genes via Tapastri platform to validate these two patterns of clonal evolution during leukemia progression unambiguously. Likewise, we captured that in persisted subclones in T593 and T856 leukemic cells attained reproductive fitness from maintaining a mutational static status with remarkable transcriptomic variation from diagnosis to relapse. To further interpret the transcriptomic signature drift in the persisted TCR-defined major clones from T593 and T856 pairs, differential expression analysis was employed with RNA-binding protein Musashi-2 (MSI2) showing the most prominent differential expression pattern across drifted subclones catching our attention as a potential indicator of intrinsic clonal progression related to chemo-resistance. Comprehensive analysis of RNA-seq data from the CCCG-ALL-2015 cohort (n=72) and TARGET T-ALL cohort (n = 264) revealed that higher levels of MSI2 mRNA expression in pediatric T-ALL were correlated with higher measurable residual disease (MRD) after induction, and significant correlation between elevated MIS2 mRNA and resistance to prednisone, daunorubicin, and cytarabine were observed from ex vivo drug response assay. RNA immunoprecipitation and high-throughput mRNA sequencing from T-ALL cell lines detected a consistent significant enrichment of MYC transcript peaks in three T-ALL cell lines, indicating the molecular mechanism of MSI2 upregulation on MYC in the progression of T-ALL. Finally, In vitro and in vivo pharmacotyping analysis further validated the MSI2 inhibition significantly sensitized T-ALL to the chemotherapeutic drugs. Collectively, our study leveraging single-cell multi-omics profiling has provided a snapshot of the clonal architecture evolution that occurs from diagnosis to relapse in T-ALL, proving the coexistence of “clonal shift” and “clonal drift” in leukemic progression. Systemic analysis of drifted T-ALL clones has provided compelling evidence of the posttranscriptional regulatory effect of MSI2 on MYC and its potential correlation with leukemic reoccurrence, pinpointing MSI2 as a promising drug target of T-ALL in the future practice.

Qiling Baitouweng Tang (QLBTWT) is a traditional clinical formula for treating diffuse large B-cell lymphoma (DLBCL), but its molecular action is not fully understood. This research is utilized in silico analysis and liquid chromatography tandem mass spectrometry (LC‒MS/MS) to identify the active constituents of QLBTWT with anti-DLBCL properties and their targets. The study identified 14 compounds, including quercetin, naringenin, and astilbin, as potentially effective against DLBCL. Molecular modeling highlighted the favorable interaction of quercetin with the JAK2 protein. In vitro studies confirmed the ability of quercetin to inhibit DLBCL cell growth and migration while inducing apoptosis and causing G2/M phase cell cycle arrest. Molecular dynamics simulations revealed that quercetin binds to JAK2 as a type II inhibitor. In vivo studies in U2932 xenograft models demonstrated that QLBTWT inhibited tumor growth in a dose-dependent manner, which was associated with the JAK2/STAT3 signaling pathway. Overall, this study elucidates the therapeutic effect of QLBTWT on DLBCL through quercetin-mediated suppression of the JAK2/STAT3 pathway, offering novel therapeutic insights for DLBCL.

目的:采用数据挖掘方法,探讨癌毒理论指导下的老年弥漫大B细胞淋巴瘤的辨治规律.方法:通过回顾性研究方法,收集倪海雯主任课题组2016年6月—2021年7月治疗老年弥漫大B细胞淋巴瘤的有效病例147例,通过MedcaseV5.2仓公诊籍国医脉案数据记录挖掘系统,运用频数分析与关联规则分析,基于癌毒病机理论从症状、病机、处方用药等多方面对于医案进行数据挖掘分析.结果:通过数据挖掘及症状、病机、药物关联分析得出,临床表现中常见症状为颈部肿块、腹痛、神疲乏力、发热,其次是纳差、寐差等,舌象中频数较高的是苔白,质红,质淡,脉象频数较高的是细、弦脉,症状病机集外高关联病机要素为"虚、毒、痰、热、瘀",气虚、癌毒为病机关键,夹杂痰、热、瘀.临床用药以扶正解毒为治则,扶正强调培补中焦,如太子参、黄芪等;消癌解毒当注意夹杂之热、痰、瘀之不同,分别采用清热解毒、化痰解毒,化瘀解毒,如半枝莲、蛇舌草、夏枯草、莪术、姜黄、浙贝母、茯苓等.结论:老年弥漫大B细胞淋巴瘤病位在脾肾,属本虚标实,本虚以脾气亏虚多见,癌毒贯穿始终,夹杂痰、瘀、热为患.临床以健脾益气,消癌解毒为主,佐以化痰、清热、消瘀.

OBJECTIVESThis study aimed to investigate the performance of Pulsatilla saponin A (PsA) in diffuse large B-cell lymphoma (DLBCL) cells.METHODSProliferation, ELISA, apoptosis, cell cycle analysis, and assays were carried out to detect the growth and apoptosis in DLBCL cells. Western blotting was used to identify the change in the protein.RESULTSIn cell assays, PsA significantly inhibited the growth and apoptosis in DLBCL cells. The IL-10 and TNF-α of OCI-LY10 and U2932 cells were reduced after 24h PsA treatment. Bax, cleaved PARP, and cleaved Caspase-3 were increased, while Bcl-2 and C-Myc decreased after PsA treatment. IL-10 may regulate the expression of C-Myc protein in cells by activating the JAK2/STAT3 signaling pathway. PsA can inhibit the overexpression of p-JAK2 and p-STAT3 signaling pathways induced by IL-10 stimulants. The proliferation and apoptosis induced by PsA were confirmed in DLBCL cells.CONCLUSIONOur findings revealed that PsA may exert its antitumor effect by causing G1 arrest and apoptosis in DLBCL cells. The mechanism of PsA regulating apoptosis in DLBCL cells is probably through the JAK2/STAT3 signaling pathway in vitro.

总结倪海雯治疗原发肠道弥漫大B细胞淋巴瘤的经验.原发肠道弥漫大B细胞淋巴瘤病情凶险,预后差,临床表现缺乏特异性,治疗棘手.倪海雯以周仲瑛癌毒学说及病机十三条理论为指导,从"虚、毒、湿、热"复合病机论治,归纳本病核心病机为"脾虚癌毒,挟杂湿热",并结合不同治疗阶段采用分期论治、病证结合的中西整合模式,在经典名方白头翁汤基础上结合癌毒病机加以创新,创立验方芪苓白头翁汤以健脾益气,燥湿清肠,标本兼治.临床随访观察发现,其可明显改善患者临床症状,减少复发,提高患者生活质量.

目的 检测初诊弥漫大B细胞淋巴瘤(DLBCL)采用R-CDOP(利妥昔单抗联合环磷酰胺、脂质体多柔比星、长春新碱及泼尼松)方案联合或不联合消癌解毒方治疗前后外周血调节性T细胞(Treg)百分比的变化,探讨Treg对于DLBCL发病及预后可能的影响以及消癌解毒方是否具有调控Treg表达的作用.方法 入组2018年1月至2022年1月南京中医药大学附属医院收治的初诊DLBCL病人共47例(治疗组24例,对照组23例)和健康对照45例,治疗组采用消癌解毒方联合R-CDOP方案,对照组单纯采用R-CDOP方案治疗,两组均化疗6个周期,采用流式细胞术检测两组病人治疗前后及健康对照的外周血CD4+CD25+CD127low Treg百分比,观察两组病人的临床疗效以及治疗前后CD4+CD25+CD127low Treg百分比的变化.结果 治疗前,治疗组及对照组两组病人和健康对照的CD4+CD25+CD127low Treg百分比中位数分别为6.01％、5.73％、7.32％,两组病人外周血Treg百分比均低于健康人(P<0.05).治疗6周期结束后,治疗组及对照组两组病人的CD4+CD25+CD127low Treg百分比中位数分别为7.33％和5.85％,治疗组Treg百分比较治疗前明显上升(P<0.05),对照组治疗前后Treg百分比变化差异不明显(P>0.05).治疗组和对照组相比,治疗组比对照组的CD4+CD25+CD127low Treg百分比明显上升(P<0.05).两组病人临床疗效评估结果比较,治疗组和对照组的总缓解率(ORR)分别为79.17％和69.56％,两组ORR差异无统计学意义(P>0.05).结论 消癌解毒方有可能通过上调DLBCL病人失衡的Treg百分比发挥调控肿瘤免疫环境的作用.

张仲景被誉为"医方之祖",其所著《伤寒杂病论》载方200余首,因其效如桴鼓,后世尊称为"经方"."经方"的组方原理蕴含了"汗、吐、下、和、温、清、消、补"八法,其中"和法"可谓治疗之基本大法.通过对《伤寒杂病论》中"和法"经方的相关条文进行梳理及查阅文献,探源和法经方对治疗恶性淋巴瘤的重要的理论依据及临床指导意义,并结合倪海雯主任运用和法的心得体会及医案,以期为恶性淋巴瘤中西医结合诊疗提供新的思路.

目的:以国医大师周仲瑛教授癌毒学说为基础,结合真实世界淋巴瘤的症状及病机要素,设计淋巴瘤中医证候量表.方法:通过查阅淋巴瘤中医证候学和症状学相关文献,结合淋巴瘤临床症状数据挖掘结果,形成量表条目池.选取江苏省中医院的淋巴瘤患者进行正式调查,分别从离散趋势法、克朗巴赫系数法、因子分析法、相关系数法4个方面考评量表的信效度.结果:共纳入受试者129例,应用以上统计方法对调查结果进行分析、汇总,删除未通过筛选的条目,确定了包含5个维度、25个条目的终选量表.结论:本研究初步形成的疗效评价量表具有良好的信效度,可客观指导中医临床治疗,为高级别临床证据的产生提供依据.

目的:通过数据挖掘及国医大师癌毒病机理论分析真实世界中西整合治疗模式下多发性骨髓瘤的症状、病机、治疗及中医治疗策略,完善癌毒病机指导下多发性骨髓瘤临床诊疗方案.方法:收录倪海雯主任 2016 年 7 月—2021 年 2 月门诊或病房收治的多发性骨髓瘤患者病历资料及医案处方,运用Medcase Ver5.2 数据挖掘系统对症状、舌脉、病机、药物进行频数、关联规则、及系统聚类分析.结果:该研究共纳入患者 71 例,382 诊次,涉及症状 101 项,舌象 16 种,脉象 9 种,病机 7 种,中药 317 味.临床症状与病机集外关联规则 31 项;病机与中药集外关联 33 项;临床症状与中药集外关联 31 项.通过高频药物聚类分析得到 5 个聚类组.结论:倪海雯主任认为,多发性骨髓瘤病位在骨髓,病变脏腑主要涉及脾、肾.基于癌毒理论"虚、毒、痰、瘀、热"核心病机要素以及病机十三条理论,该病病机总属脾肾亏虚,癌毒内蕴,治疗上以健脾益肾,抗癌解毒为根本.癌毒多有夹杂,区分"痰、热、瘀、虚"之夹杂,分别投以化痰解毒、清热解毒、化瘀解毒、扶正解毒.新药时代该病的临床决策以中西整合,病证结合,分期分阶段,复法组方为原则.

总结倪海雯教授基于癌毒病机整合治疗老年弥漫大B细胞淋巴瘤的经验.老年弥漫大B细胞淋巴瘤以癌毒病机为核心,临证常见"痰、热、瘀、毒、虚"五大病机要素,且多种病机相互兼夹、转化、复合为患.倪海雯教授论治老年弥漫大B细胞淋巴瘤以消癌解毒贯穿始终,采用"分期整合,减毒增效",复法大方多环节增效,与化疗药、靶向药等西药及虫类药等中药有机结合,同时注意顾护正气,标本兼顾.附1则典型病案.

"态靶理论"是仝小林院士提出的现代中医临床辨治新策略,将传统中医的辨证与现代医学的疾病认识相结合,将中医的宏观调态与现代医学的微观打靶相结合,针对疾病、症状、临床指标选取靶方靶药,建立整体观和精准化相融合的中西医整合新模式.导师倪海雯基于癌毒病机及态靶理论指导多发性骨髓瘤的临床诊疗,认为该病以肾虚癌毒为核心病机,夹杂"痰、热、瘀、虚",多因复合;以补肾解毒、宣痹通络为治则,贯穿始终,创立验方宣痹消瘤方作为疾病之"靶方";辨析"痰、热、瘀、虚"之夹杂病机,分别投以化痰、清热、消瘀、补虚以调态;针对骨痛、肾损等并发症分别施以对症之靶药;针对高黏滞血症、单克隆球蛋白增高结合施以标靶药物.探索"癌毒-态靶理论"指导下的中西医结合创新模式契合多发性骨髓瘤新药时代的诊疗实践.

弥漫大B细胞淋巴瘤是一种侵袭性非霍奇金淋巴瘤,其中老年患者发病率高,组织器官严重退化、全身并发症多,临床特征多变,误诊率高,确诊时多处于分期较晚阶段,预后极差.目前一线化疗联合分子靶向治疗在老年患者中面临治疗不耐受、并发症多、易复发耐药等临床难点.针对老年弥漫大B细胞淋巴瘤临床实践中的现状及难点,结合国医大师周仲瑛癌毒病机理论,系统阐释该病的病因病机、辨治要点、整合中西医治疗的优势及治疗策略,结合新药时代老年患者分层管理理念,以及本中心淋巴瘤真实世界临床干预实践,为广大中医临床工作者提供理法方药齐备的全程管理模式,以癌毒病机理论指导老年弥漫大B细胞淋巴瘤的整合治疗,建立更加系统的临床干预范式.从而改善患者脏器功能,控制并发症,减少复发,提高生命质量,发挥中医药减毒增效的独特优势、达到节约医疗成本的目的.

目的 探讨项目管理对提高老年病人肠镜检查肠道准备清洁率的效果. 方法 2020年7～12月,我科针对老年病人肠镜检查前肠道准备过程中可能存在的问题进行了项目管理,选择该时期我科收治的70例肠镜检查老年病人为研究对象,同时选取2020年1～6月开展项目管理前的70例老年病人作为对照组,比较2组肠道准备清洁率以及病人出院护理满意度的差异. 结果 项目管理实施后,肠镜检查治疗病人的肠道清洁率由实施前的94.78％提高至97.99％,出院病人护理工作满意度由实施前的98.82％提高至99.9％. 结论 项目管理可以提高老年病人肠镜检查肠道准备清洁率,有利于提高肠镜检查治疗效果,提高护理质量及病人满意度.

OBJECTIVE To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. METHODS CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. RESULTS Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). CONCLUSION Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.

恶性淋巴瘤为现代病名,治疗当以辨病结合辨证为主.改善生存、控制并发症、减少复发是中西结合优化治疗淋巴瘤的策略.在淋巴瘤并发症的管理中,胃肠道并发症较为多见,其发病与疾病本身、药物、感染等密切相关,病机复杂多变,治疗棘手.倪海雯长期从事恶性淋巴瘤的中西医整合治疗,临证中发现恶性淋巴瘤胃肠道并发症常见寒热错杂证,治疗借鉴仲景寒热错杂之病机、取半夏泻心汤之方义,调气机、平升降、寒温并用,顾护后天脾胃,疗效显著.

目的:阐述国医大师周仲瑛教授癌毒病机理论指导下蕈样肉芽肿的病因病机及辨证治疗.方法:基于癌毒病机理论对蕈样肉芽肿的病因病机及辨证治疗进行系统阐释,回顾目前西医治疗的现状及难点,结合具体病案论述中西结合治疗的辨证思路.结果:对疾病早期患者采用以皮肤为靶向的局部治疗,中医辨证多为风热,以祛风清热、凉血解毒为主要治法.随着疾病的进展,采用全身系统治疗为主,病机属虚实夹杂,以益气养阴、凉血解毒为主要治法.结论:蕈样肉芽肿早期诊断困难,确诊主要依靠病理形态学及免疫组织化学.西药综合治疗效果不理想,中医治疗结合癌毒病机理论,分期分阶段紧扣核心病机,可有效控制症状,提高患者生命质量.

多发性骨髓瘤(Multiple myeloma,MM)是骨髓中浆细胞恶性增殖并异常分泌单克隆免疫球蛋白或轻链,引起溶骨性损害、高钙血症、贫血、肾功能损害等临床特征的造血系统恶性肿瘤.导师倪海雯长期从事中西医整合优化治疗多发性骨髓瘤的临床研究,基于国医大师邹燕勤治疗肾脏病的经验,结合多发性骨髓瘤临床的特点,认为多发性骨髓瘤肾损伤以脾肾亏虚为本,痰浊瘀热为标,治疗在标本兼顾的基础上,宜以健脾益肾、淡渗清利为主,在临床治疗中可起到明显的减毒增效、改善患者生存质量、加快肾损伤恢复等积极作用.