Inhomogeneous distribution and inadequate accumulation of antitumor drugs in solid tumors significantly limit their therapeutic effectiveness. There is a pressing need for methods that enable uniform and sustained delivery of therapeutics throughout these tumors. In this study, we present a gas vesicle-mediated therapeutic designed for spatiotemporal distribution in ultrasound-assisted photothermal therapy for solid tumors. Indocyanine green (ICG) is efficiently conjugated to the surface of gas vesicles through dopamine self-polymerization, which demonstrates enhanced photothermal stability and a high photothermal conversion efficiency of similar to 35%, together with an approximately 2-fold higher reactive oxygen species generation than free ICG. Following ultrasound treatment, the biohybrids can fragment and infiltrate solid tumors, achieving homogeneous distribution and retention within the tumor. This targeted spatiotemporal delivery leads to significant suppression of tumor growth and extended survival in tumor-bearing mice. Additionally, due to their capacity to disrupt ribosomes and recruit immune cells, these well-designed nano biohybrids offer a viable approach for the effective spatiotemporal distribution of drugs in solid tumors, thereby enhancing antitumor efficacy with high efficiency.

Objective: Laminin subunit Beta-1 (LAMB1), a component of the extracellular matrix, has been reported to be implicated in the development and progression of cancer. However, the role of LAMB1 in Nasopharyngeal Carcinoma (NPC) remains unknown. Methods: Three NPC datasets were utilized to identify LAMB1 as a targeted gene. The correlation between LAMB1 expression and clinical characteristics, prognosis was explored. KEGG and GO enrichment analyses were conducted to investigate LAMB1’s functions in NPC. The CIBERSORT, xCell, MCPCOUNTER, and EPIC methods were used to assess the Cancer-Associated Fibroblasts (CAFs) and immune cells infiltration. We predicted LAMB1’s effect on treatment using TIDE, CTRP, and CellMine databases. Finally, Western blot, CCK-8, Transwell, and Wound scratch were employed to validate LAMB1’s effect on NPC cells. Results: LAMB1 was highly expressed in NPC. High-expression LAMB1 was correlated with poorer progression-free survival and impeded the infiltration of CD4+ T-cells, CD8+ T-cells and dendritic cells. It also diminished the expression of HLA and suppressed T-cells stimulation. Differential expressed cytokines and involved pathways were divergent across different level of fibroblasts infiltration. At high level of fibroblasts, LAMB1 indirectly inhibited immune cells by remolding extracellular matrix. But at low level of fibroblasts, LAMB1 directly suppressed immune response. Tumors with high LAMB1 level had weak responses to immunotherapy. In vitro experiment, LAMB1 significantly suppressed HLA-1 and enhanced the proliferation, migration, and invasion capabilities of NPC cells. Conclusion: High expression of LAMB1 is significantly associated with an immune-suppressive tumor microenvironment in NPC. LAMB1 enhances the proliferation, migration and invasion of NPC cells. These findings suggest that LAMB1 may serve as a prognostic biomarker for predicting NPC progression and a potential therapeutic target to enhance the efficacy of existing immunotherapies. Level of evidence: 3.

BackgroundThe current progressive increase in the cancer burden of prostate cancer requires the exploration of new diagnostic and therapeutic approaches. Nanobodies are single-domain antibodies with the advantages of small size, high stability, easy processing and modification, which are increasingly used in the treatment of many types of cancer.MethodsThis review analyzed the relevant literature in PubMed and other databases.ResultIn the retrieved literature, nanobodies are widely used in the treatment of prostate cancer. The preparation of nanobodies targeting PSA or PSMA is straightforward. For diagnostic purposes, nanobodies can be used in the preparation of biosensors for more sensitive identification of prostate cancer; for therapeutic purposes, nanobodies are used in the preparation of immunotoxic and ADC drugs. Preclinical in vivo and in vitro experiments have shown that this therapeutic approach is feasible. This article is a review of the above to provide new ideas for the treatment of prostate cancer.ConclusionCompared with traditional antibodies, nano-antibodies have the advantages of small size, high stability, and high penetration. These advantages make nano-antibodies worthy to be widely used. Current studies have shown that nanobodies have advantages and future in the diagnosis and treatment of prostate cancer.

With the change of people’s lifestyle and diet structure,the incidence of breast cancer in women is getting higher and higher.Surgery occupies an important position in the treatment of breast cancer,but surgery seriously damages the body’s righteousness,and the appearance changes caused by the treatment often further increase the patient’s psychological burden,causing patients to experience a series of discomfort symptoms after surgery. Traditional Chinese medicine has a significant effect on improving patients’ postoperative symptoms. Professor JIA Yingjie believes that breast cancer always belongs to deficiency in origin and excess in superficiality,and its pathogenesis is “positive qi internal deficiency,coexistence of poison and blood stasis”. However,surgery often consumes right qi,so patients with postoperative qi deficiency and blood stasis are more common. Professor JIA Yingjie’s treatment of fatigue after breast cancer surgery is mainly based on qi supplementation,and at the same time,the four methods are used in combination with the qiassisting method,the qi-adjusting evil-inducing method,the qi-adjusting transport method and the Chinese method. Guben,the ventilator can be adjusted smoothly,which can effectively relieve the postoperative adverse reactions of the patient,and at the same time improve the patient’s immunity and prevent the metastasis and recurrence of the tumor.

目的:评价针灸疗法治疗压力性尿失禁系统评价的方法学质量、报告质量以及结局指标证据质量.方法:计算机检索Cochrane Library、Embase、PubMed、CBM、CNKI、万方数据库、维普数据库,检索时限均从建库至2022年3月27日,检索文献限定为中英文文献,筛选纳入针灸治疗压力性尿失禁的系统评价.使用AMSTAR2量表、PRISMA声明和GRADE系统对纳入研究的方法学质量、报告质量及证据质量进行评估.结果:共纳入SR 9篇,其中3篇评价为低质量,其余研究为极低质量.根据PRISMA声明评价报告质量结果显示:除1篇SR为低质量以外,大部分研究报告质量评价结果较好,得分区间在18-23.5分.对主要结局指标进行GRADE证据质量评级结果显示,所纳入SR的结局指标质量评级不理想,中级质量证据仅占10.3％,低级与极低级质量证据占89.7％.结论:对于压力性尿失禁的治疗,针灸疗法较盆底肌训练及药物治疗更具优势,但目前相关系统评价在方法学、证据质量不理想,相关研究的报告仍需进一步规范并提高研究总体质量.

Radical prostatectomy is considered to be the best treatment for patients with localized and locally advanced prostate cancer. Unfortunately, post-prostatectomy urinary incontinence (PPUI) is a common complication, with an incidence ranging from 4% to 31%.1 PPUI can adversely affect quality of life and cause emotional and financial distress. For most patients, PPUI improves to near baseline levels within 12 months of surgery. However, only a minority of patients with residual PPUI at 12 months experience sustained improvement. Implantation of an artificial urinary sphincter (AUS) represents the gold standard of treatment, although its widespread adoption is limited due to high costs and a significant risk of requiring surgical revision. Hence, early intervention to facilitate patient recovery within 12 months is desirable. For persistent PPUI patients, especially the elderly, we hope to find a safe and non-invasive treatment option that can improve symptoms. Acupuncture is widely used in the treatment of various types of urinary incontinence due to evidence of its effectiveness, the simple nature of the procedure, and its minimal side effects. Electroacupuncture can reduce urine leakage in women with stress urinary incontinence (SUI),2 but relatively little is known about its efficacy and safety for men with PPUI, in whom the quality of evidence is considered to be low. Herein, we report on the use of acupuncture in five patients with persistent PPUI who received routine clinical care at our center.

目的 分析国内外的前列腺癌临床研究注册情况,以期为国内前列腺癌的研究提供参考.方法 通过检索自建库以来美国ClinicalTrials.gov数据库注册的前列腺癌临床研究,分析中国注册的前列腺癌临床研究在样本量、试验进展、研究类型、试验设计、盲法使用、临床分期、试验目的、结局评价等方面的特点.结果 全球已注册的前列腺癌临床研究共374 001项,其中前列腺癌研究5 046项,我国前列腺癌临床研究共274项,与欧美国家差距较大;我国前列腺癌临床试验样本量以100～999例最多;试验类型以干预性研究为主(222项,81.02％),其次是观察性研究(47项,17.15％);干预性研究的研究模式以随机平行对照为主,观察性研究的试验模式以队列研究为主;研究目的主要以"治疗"为目的(70.65％);治疗以药物干预为主(58.7％);临床试验分期以Ⅲ期临床试验(33.7％)比例最高;主要结局指标方面,我国以总生存、安全性为主要结局观察指标.结论 我国前列腺癌临床试验的研究现状和发展态势与世界前列腺癌注册临床研究相比,仍需加强研究模式多样化.此外,较为早期的原创性临床试验数量尚需进一步提高.

MET exon14 (METex14) skipping mutation is an independent driver gene in non-small cell lung cancer (NSCLC) . About 3%-4% of NSCLC patients carry METex14 skipping mutation. These patients have poor prognoses and poor responses to traditional chemotherapy and immunotherapy. Highly selective MET inhibitors such as capmatinib, tepotinib, savolitinib have shown good efficacy and safety data in clinical trials, which bring new treatment options for patients with METex14 skipping mutations.

目的:观察"健脾利湿化瘀方"联合雄激素受体抑制剂/雄激素合成抑制剂+促性腺激素释放激素激动剂(MAB)治疗激素敏感性前列腺癌(hormone-sensitive prostate cancer,HSPC)的临床疗效.方法:选取2019年11月至2021年6月于天津中医药大学第一附属医院、天津医科大学总医院就诊的HSPC患者100例,随机分为治疗组和对照组各50例,对照组接受MAB治疗,治疗组在对照组基础上给予"健脾利湿化瘀方".主要观察指标为中位无进展生存期(median progression-free survival,mPFS)、前列腺特异性抗原(prostate specific antigen,PSA);次要观察指标为血清睾酮、中医临床症状评分、肿瘤生存质量调查表(EORTC QLQ-C30)、KPS功能状态评分.结果:治疗组较对照组可延长mPFS 4个月(16个月vs.12个月)、明显降低PSA水平、改善中医临床症状、改善QLQ-C30、提高KPS评分(均P<0.05).亚组预后因素分析显示,治疗前KPS评分 90分组、PSA最低值≤1 ng/mL、PSA下降≥90％的患者在治疗组中获益更显著.结论:"健脾利湿化瘀方"联合MAB治疗延长患者的mPFS,更好地降低PSA水平,实现PSA的深度应答,降低血清睾酮至去势水平,延长激素敏感时间,改善中医临床症状,提高患者的生存质量.

贾英杰教授认为前列腺癌的核心病机为"本元亏虚,癌浊丛生",治疗应根据病程分期,活用"黜浊"与"培本"之法.观察等待期,邪不盛、正未虚,治疗当黜浊为主,辅以培本以增强黜浊力度;手术治疗阶段,患者元气耗伤,治疗重在培本,可从补气血入手,用药宜轻灵;放疗阶段,火邪内攻,耗气伤阴,患者常见膀胱、大肠血络损伤或阴津耗伤,治疗总原则为消补兼施、培本与黜浊并举;去势敏感期,针对内分泌治疗所致潮热等不良反应,治以补益肾精;去势抵抗期,患者气血亏耗,正气大虚,治以健旺正气为要,从脾入手,善用黄芪.附验案一则.

Regucalcin (RGN) is a potent inhibitory protein of calcium signaling and expresses in various tissues. However, the role of RGN in the tumor immunological microenvironment in lung squamous cell carcinoma (LUSC) remains unclear. This study identified the expression of RGN from public databases and immunohistochemistry with clinical specimen. The association between RGN and the tumor immune microenvironment (TIME) was investigated in LUSC by ESTIMATE and CIBERSORT algorithms. Similarly, the Tumor IMmune Estimation Resource (TIMER) database was used to identify the correlation between RGN and immune cells. The ceRNA network was established based on the data obtained from public databases. Finally, prediction of drug response to chemotherapy and immunotherapy was performed to evaluate clinical significance. This study found that RGN expression was significantly downregulated in tumor tissues and closely related to clinical factors and prognosis of LUSC patients. Differentially expressed genes (DEGs) grouped by the expression of RGN were mostly involved in immunobiological processes such as humoral immune response and leukocyte mediated immunity. RGN and its related miRNA (has-miR-203a-3p) and lncRNAs (ZNF876P and PSMG3-AS1) constructed the novel prognosis-related ceRNA network. Plasma cells, T cells CD4 memory resting, Macrophages M0, Macrophages M1, Mast cells resting, Mast cells activated and Neutrophils showed significantly different levels of infiltration between high and low RGN expression groups. The TIMER database showed that RGN expression was positively correlated with certain immune infiltrating cells. High RGN expression group showed a higher TIDE score, a higher dysfunction score and a lower MSI score, presenting a possible lower efficacy after accepting the immunotherapy than low RGN expression group. RGN expression was closely associated with prognosis of LUSC patients and played an important role in tumor microenvironment. This suggests that RGN could be a promising biomarker for assessing immunotherapy efficacy and prognosis.

[Objective]To explore the mechanism of Xiaoyan Decoction in the treatment of gastric cancer by network pharmacology.[Methods]TCMSP、TCMID and BATMAN-TCM database was used to screen the active ingredients and targets of Xiaoyan Decoction,and UniProt was used to obtain the corresponding gene names of protein targets;the gastric cancer disease targets were mined through DrugBank,GeneCardsand OMIM database,and the intersection genes with Xiaoyan Decoction target genes were screened;the drug compound intersection target network was drawn by using Cytoscape 3.7.2 software;the String number was used to calculate the sequence the PPI network was constructed according to the analysis platform,and the MCODE plug-in was used for cluster module analysis of PPI network;the Metascape database was used for KEGG enrichment analysis and GO enrichment analysis;the Kaplan-Meier Plotter database was used to explore the impact of key gene targets on OS of gastric cancer patients,and the survival curve was drawn.[Results]41 active components,266 target genes,1 163 gastric cancer target genes and 116 cross genes were obtained,and 35 compounds were obtained after eliminating the active components without cross genes.TP53,JUN,AKT1,MAPK3,RELA,MAPK1,ESR1,MAPK14 and IL-6 are the key targets of Xiaoyan Decoction in the treatment of gastric cancer.The results of GO enrichment analysis showed that it was related to the signal pathway of apoptosis,response to inorganic substances,response to oxidative stress and response to chemical stress.The results of KEGG pathway enrichment analysis showed that it was mainly related to proteoglycan,PI3K-Akt signal pathway,IL-17 signal pathway,TNF signal pathway and platinum resistance in cancer.Survival analysis showed that the overall survival of patients with high expression of TP53,AKT1,MAPK3,RELA and ESR1 was significantly lower than that of low expression group,while the overall survival of patients with high expression of JUN,MAPK1 and MAPK14 was significantly higher than that of low expression group.[Conclusion]The research methods based on network pharmacology can help to find the key targets and signal pathways of Xiaoyan Decoction in the treatment of gastric cancer,and provide useful information and data support for further exploring the mechanism of Xiaoyan Decoction in the treatment of gastric cancer.

Among the common malignant tumors in men worldwide, the incidence of prostate cancer ranks second to lung cancer. This disease will bring an economic burden to patients and their families and can reduce the quality of life of patients. Researchers have conducted numerous clinical trials on the efficacy and safety of different interventions in the treatment of prostate cancer with traditional Chinese medicine (TCM) combined with standard treatment regimens. However, the currently published clinical trials exhibit inconsistent and irregular reporting of outcome measures. The objective of this paper is to emphasize the need for a core outcome set (COS) to facilitate future prostate cancer research, aiming to improve the quality of trials and generate high-quality evidence. This mixed methods project has three phases, as follows: (1) a scoping review of the literature to identify outcomes that have been reported in clinical trials and systematic reviews of interventions involving TCM for the treatment of prostate cancer as well as a qualitative component using interviews to obtain the views of patients with prostate cancer, their families, and their caregivers who have a history of TCM treatment; (2) a Delphi survey among stakeholders to prioritize the core outcomes—Participants will include traditional Chinese and Western medicine clinicians in prostate cancer–related directions, nurses, and methodology experts who will participate in 2 rounds of the Delphi method expert consultation to score each outcome in the list of outcome indicators; and (3) a face-to-face consensus meeting to discuss and agree on the final COS for the application of TCM in the treatment of prostate cancer. The protocol has been registered in PROSPERO (CRD42022356184) before the start of the review process, and we will initiate the review on August 1, 2023; results should be expected by September 1, 2023. The Delphi survey among stakeholders is expected to start in October 2023. The development of a core outcome set for assessing clinical safety outcomes of prostate cancer in clinical trials of TCM will provide a significant first step to assist Chinese doctors, researchers, and policy makers. PROSPERO CRD42022356184; https://tinyurl.com/ysakz74r PRR1-10.2196/46794

目的:评价消岩汤联合卡瑞丽珠单抗+安罗替尼治疗方案对一线治疗失败的晚期非小细胞肺癌(NSCLC)患者的临床疗效及安全性.方法:纳入2020年12月1日—2021年6月31日就诊于天津中医药大学第一附属医院的晚期NSCLC患者55例,随机分为对照组(27例)和试验组(28例).对照组给予卡瑞丽珠单抗+安罗替尼治疗,试验组给予消岩汤联合卡瑞丽珠单抗+安罗替尼治疗.比较两组疗效、生活质量,治疗前后患者的血清肿瘤标志物、血清VEGF水平、T淋巴细胞亚群计数变化及不良反应.结果:试验组中位无进展生存期(PFS)较对照组延长0.82个月(8.55个月vs 7.73个月),试验组疾病控制率(DCR)、客观缓解率(ORR)高于对照组(57.1％vs 40.7％,14.3％vs 7.4％),但差异无统计学意义(P>0.05);治疗后试验组血清VEGF水平、CEA、CYFRA21-1降低情况优于对照组(P<0.05);试验组血液CD4+/CD8+、CD3+、CD4+、NK细胞数目上升情况高于对照组(P<0.05);生活质量方面,试验组卡氏评分、中医证候积分情况优于对照组(P<0.05);不良反应方面,试验组WBC减少、RBC减少、消化道反应、疲乏发生低于对照组(P<0.05).结论:消岩汤联合卡瑞丽珠单抗与安罗替尼二线及以上治疗晚期NSCLC,可以增强患者免疫功能,降低血清肿瘤标志物及VEGF水平,减少西医治疗引起的毒副作用,改善生活质量.

肾虚是前列腺癌发病内在因素,当代医家多通过补肾治疗前列腺癌,然而部分补肾中药有类雄激素样作用,可促进前列腺癌发展,是临床治疗矛盾点.肾中精气有赖脾化精微以充养,故肾虚亦可从脾论治.前列腺癌的治疗立足于"虚、浊、毒"等核心病理因素,以"黜浊培本"理论为指导原则,以"健脾利湿、解毒祛瘀"为治疗之法,以"平"为期,根据病情分期以及正气强弱和邪气盛衰的程度,调整攻补法度,动态辨治,权衡攻补,顾护中州调理脾胃,形成前列腺癌的特色治疗理论.

前列腺癌是男性常见泌尿系统恶性肿瘤,发病率逐年增高,中医药在其综合治疗中占据重要地位.中医属"癃闭""淋证"等范畴,从古籍挖掘至临床四诊合参,切入"浊毒致癌"因机,分析前列腺癌的证候要素和中医辨治,为临证动态运用"黜浊培本"法辨治前列腺癌提供思路.

目的 基于CiteSpace客观展示近20年来中医药治疗癌痛领域的发展现状及研究前沿.方法 以中国知网、维普、万方三大数据库以及Web of Science核心合集收录的2000-01-01至2021-08-08中医药治疗癌痛研究相关中英文文献为研究对象,利用CiteSpace V软件对文献的作者、机构、关键词分别进行统计分析并绘制相关科学知识图谱.结果 共1982篇中文文献、215篇英文文献纳入分析,近20年来,中医药治疗癌痛领域的发文量总体呈上升趋势;各作者普遍发文量较低,核心团队尚未形成,其中发文量最高的核心学者为冯利教授;国内主要研究机构为南京中医药大学、湖南中医药大学、辽宁中医药大学附属医院、中国中医科学院广安门医院和上海中医药大学附属龙华医院,国外主要研究机构为美国的Mem Sloan Kettering癌症中心和韩国的庆熙大学,各机构间合作以地域聚集为主,跨地域的科研机构合作尚少;关键词聚类分析分别形成了13个具有代表性的聚类;肝癌与乳腺癌所致癌痛、中医护理和阿片类药物相关性便秘在近几年来得到了显著关注.结论 中医药治疗是西医治疗的重要补充辅助手段,中西医结合治疗癌痛是未来的发展趋势.然而,中医药治疗癌痛领域的研究仍处在发展阶段,尚无突破性进展,"各自为政"的研究格局一定程度上限制了该领域的进一步发展.

目的:探讨局部高危前列腺癌患者的免疫组织化学指标与中医证型的相关性.方法:选取2019年1月至2019年12月于天津中医药大学第一附属医院和天津医科大学总医院确诊的50例局部高危前列腺癌患者的临床资料,采用神经内分泌细胞的标记物嗜铬粒蛋白A(CgA)和突触素(Syn)及标志增殖细胞活性的Ki-67指数等免疫组织化学法指标,根据患者舌苔脉象,结合局部和全身症状进行临床中医辨证分型分析.结果:局部高危前列腺癌患者的免疫组织化学指标表达情况中,Ki-67指数增高为最常见情况(P＜0.05).50例患者中,湿热蕴结证及肝肾阴虚证为最常见证型(P＜0.05).湿热蕴结证与Ki-67指数增高、CgA阳性具有相关性,瘀毒内结证与Ki-67指数增高、Syn阳性亦具有相关性,提示两证型预后较差(均P＜0.05).结论:辨证为湿热蕴结证和瘀毒内结证的局部高危前列腺癌患者,肿瘤组织中多存在神经内分泌分化倾向,且细胞增殖活性较高,肿瘤恶性程度增加,增殖迅速,更易进展为激素非依赖性前列腺癌,从而耐受内分泌治疗.在西医内分泌治疗的基础上,应尽早结合中医辨证情况,充分发挥中医药辨证论治的优势,尽可能延缓疾病进展.

Breast cancer is a kind of malignant tumor disease that poses a serious threat to human health. Its biological characteristics of rapid proliferation and delayed angiogenesis, lead to intratumoral hypoxia as a common finding in breast cancer. HIF as a transcription factor, mediate a series of reactions in the hypoxic microenvironment, including metabolic reprogramming, tumor angiogenesis, tumor cell proliferation and metastasis and other important physiological and pathological processes, as well as gene instability under hypoxia. In addition, in the immune microenvironment of hypoxia, both innate and acquired immunity of tumor cells undergo subtle changes to support tumor and inhibit immune activity. Thus, the elucidation of tumor microenvironment hypoxia provides a promising target for the resistance and limited efficacy of current breast cancer therapies. We also summarize the hypoxic mechanisms of breast cancer treatment related drug resistance, as well as the current status and prospects of latest related drugs targeted HIF inhibitors.

目的 研究六味地黄汤合三圣散联合唑来膦酸治疗前列腺癌骨转移的作用及机制.方法 将前列腺癌骨转移小鼠随机分为模型组、六味地黄汤合三圣散组、唑来磷酸组和联合组,给予药物干预2周,采用ELISA法检测血清中碱性磷酸酶(alkaline phosphatase,ALP)活性;采用全自动生化分析仪检测血清中丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)活性及尿肌酐(urine creatinine,CRE)、尿素氮(urine urea nitrogen,BUN)、血钙、血磷水平;采用Western blotting法检测股骨组织中p63、C-X-C基序趋化因子受体4(C-X-C motif chemokine receptor 4,CXCR4)和基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)蛋白表达.结果 与模型组比较,六味地黄汤合三圣散与唑来膦酸联用显著降低小鼠血清中ALP、AST、ALT活性及CRE、BUN、血钙、血磷水平(P＜0.05),显著上调股骨组织中p63表达(P＜0.05),显著下调股骨组织中CXCR4和MMP9表达(P＜0.05).结论 六味地黄汤合三圣散联合唑来膦酸能够通过上调p63表达,抑制CXCR4和MMP9表达,从而延缓前列腺癌骨转移进程.