Background Tiao-Shen-Zhi-Ai Formula (TSZAF) is a compound prescription of traditional Chinese medicine used clinically for the treatment of ovarian cancer. In this study, we selected three main active ingredients from TSZAF and combined them into a new TSZAF monomer combination (TSZAF mc) to investigate its effects and mechanisms on inhibiting ovarian cancer proliferation and inducing apoptosis. Methods The effects of TSZAF mc on proliferative activity and apoptosis in ovarian cancer HEY and SKOV3.IP1 cells were assessed in vitro using CCK-8 assay, colony formation assay, and apoptosis assay. Micromethods, flow cytometry, and immunofluorescence were employed to evaluate the impact of TSZAF mc on aerobic glycolytic metabolites and mitochondrial membrane potential. The mRNA and protein expression of key glycolytic genes were detected by quantitative real-time PCR (RT-PCR) and Western blot (WB). An ovarian cancer subcutaneous tumor model was established in NOD-SCID mice using SKOV3.IP1 cells. TSZAF mc was administered via continuous intraperitoneal injection, and its antitumor efficacy in vivo was assessed through anatomical observation, hematoxylin and eosin (H&E) staining, and immunohistochemistry (IHC). Further RT-PCR, WB, and IHC were performed to validate the expression of key upstream glycolytic genes at mRNA and protein levels. Drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) were used to confirm binding targets. Molecular docking was performed to predict the binding interactions between the monomers and AKT. Finally, the regulatory relationships within signaling pathways were elucidated based on functional assays. Results TSZAF mc effectively inhibited ovarian cancer proliferation and induced apoptosis. It reduced lactate and ATP production, downregulated mitochondrial membrane potential, and decreased the mRNA and protein expression of key glycolytic genes, including HK2, PKM2, PFKM, GLUT1, and LDHA. In vivo, TSZAF mc suppressed ovarian cancer growth. Moreover, TSZAF mc downregulated the expression of phosphorylated AKT (p-AKT) and phosphorylated FOXO3A (p-FOXO3A) at both protein and tissue levels. CETSA and DARTS demonstrated that TSZAF mc binds AKT. The AKT activator SC79 reversed the inhibitory effects of TSZAF mc on ovarian cancer proliferation and the downregulation of glycolytic proteins. Conclusion TSZAF mc inhibits ovarian cancer progression by regulating the AKT/ FOXO3A-mediated glycolysis pathway, which may represent one of the mechanisms underlying the clinical efficacy of TSZAF in ovarian cancer treatment.

Abstract Background: Metastasis remains the leading cause of high mortality in non-small cell lung cancer (NSCLC), but early detection is challenging due to the limited sensitivity and specificity of current imaging methods. Peripheral immune markers offer predictive potential, yet their clinical use is limited by a lack of interpretable models. This study developed and validated an interpretable peripheral immune score (PIS) using machine learning (ML) to aid early diagnosis of NSCLC metastasis. Methods: We conducted a multicenter cross-sectional study of NSCLC patients in China. A derivation cohort of 309 patients from three campuses of Shanghai Hospital of Traditional Chinese Medicine (March 2023-May 2025) was split 8:2 for training and validation. Baseline data and 37 peripheral immune markers were collected. Causal inference screened predictive markers, and eight ML algorithms were applied. Model performance was assessed using AUC, decision curve analysis, and calibration. The best model was interpreted using SHAP and deployed as an online PIS Calculator. Results: The Random Forest (RF) model showed the highest performance. After feature reduction, a final interpretable RF model with 19 features accurately predicted metastasis in the validation set (AUC = 0.942). This model was translated into the Intelligent Peripheral Immunity Score (PIS), identifying high-risk patients even without radiographic evidence. Conclusion: The PIS system integrates peripheral immune markers with ML to provide an accurate, interpretable tool for early detection of NSCLC metastasis, overcoming limitations of conventional imaging and complex models, and offering a clinically actionable solution for improved patient management. Citation Format: Fan Xu, Bin Luo, Jianhui Tian, Zhenyang Cheng, Yuan Yao, Youjun Liu, Xiaoyu Yang, Jiangliang Yao, Wang Yao, Xinyi Lu, Yuchen Bao, Yiyang Zhou, Jianchun Wu, Minghua Li, Wenfei Shi, Yajing Cui, Yanhong Wang, Yunxia Wu, Yun Yang, Yan Li. Identification and validation of an explainable predictive model for early diagnosis of non-small cell lung cancer metastasis: A peripheral immune score based on integrative machine learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5091.

Background: Psychoneurological symptom clusters (PNSCs) are common in patients with ovarian cancer and are associated with reduced quality of life, treatment interruption, and poor prognosis. However, effective interventions for PNSCs remain limited. Traditional Chinese medicine may provide comprehensive benefits for symptom management. Objective: This study aims to evaluate the efficacy and safety of the TiaoShenZhiAi (TSZA) regimen in alleviating PNSCs in patients with ovarian cancer and to assess its effects on quality of life and survival outcomes. Methods: A total of 316 patients with ovarian cancer aged 18 to 70 years with PNSCs will be included and randomly divided into 2 parallel groups. Both groups will receive standard treatment for ovarian cancer as the basic treatment. The intervention group will receive the TSZA regimen, that is, Compound Ciwujia Granules (containing Acanthopanax senticosus and Schisandra chinensis) combined with psychological intervention. The control group will receive a low-dose active control (simulated Compound Ciwujia Granules) combined with psychological intervention. The primary outcome is the remission rate of PNSCs at 3 months. The secondary outcome measures include the Pittsburgh Sleep Quality Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 scale, the revised Piper Fatigue Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Quality of Life Scale, the traditional Chinese medicine syndrome scale, sleep quality, sleep diary, and the 1-year survival analysis. In addition, this study also includes a series of exploratory indicators (including functional magnetic resonance imaging, biomarkers of peripheral blood and tumor tissue, proportion of immune cells, cytokine levels, hypothalamic-pituitary-adrenal axis function, and immune gene expression analysis) and safety indicators (including vital signs, liver and kidney function, and electrocardiogram). The study outcomes will be evaluated based on different indicators during the treatment period (baseline and the 1st, 2nd, and 3rd mo of enrollment) and the follow-up period (the 6th, 9th, and 12th mo of enrollment). Data analysis will be conducted using R (version 4.5.3) software. A one-sided P value of <.03 will be considered statistically significant. Results: This study is designed to enroll a total of 316 participants. Participant enrollment is set to commence in October 2025, with no recruitment having occurred as of April 2026. The recruitment period will extend until September 2028 or until the target enrollment is met. Data analysis is scheduled for November 2028, with submission of the trial results to a peer-reviewed journal anticipated by May 2029. Conclusions: This study will evaluate the efficacy of the TSZA regimen in managing PNSCs in patients with ovarian cancer and generate clinical evidence for a new therapeutic option that improves quality of life and alleviates the symptom burden.

ObjectiveTo explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. MethodsA cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. ResultsThe prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. ConclusionDepression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.

Lung cancer remains the leading cause of cancer related deaths worldwide. Immunotherapy and combination therapies, involving chemotherapy, radiotherapy, and tumor anti-angiogenesis therapy, have shown promising clinical results and are expected to become a key approach in the future management of lung cancer. However, due to immune resistance, immunotherapy remains highly effective in only a subset of patients, while many others either do not respond initially or develop resistance over time. Moreover, immune-related adverse events induced by immunotherapy, further complicate treatment outcomes and prognosis. Immune-related biomarkers and ImmuneScores have driven the development of personalized immunotherapy strategies for lung cancer, and they can aid in predicting immune resistance, and forecasting immune-related adverse events (irAEs). This review summarizes the prognosis value of immune-related biomarkers and ImmuneScores in immunotherapy and combination therapies for lung cancer. The aim is to provide a foundation for personalized treatment and management of lung cancer, while offering guidance for future research directions in immunotherapy.

BACKGROUND: Circulating tumor cells (CTCs) serve as the “seeds” of tumor metastasis, and the clustering of CTCs is critically associated with tumor metastasis and the mortality of lung cancer patients. Inhibiting the survival of CTC clusters represents a pivotal strategy for anti-lung cancer metastasis therapy. This study is designed to explore the impact and underlying mechanism of lung cancer CTC clusters in mediating resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), thereby offering novel insights into anti-lung cancer metastasis treatment. METHODS: Using the human lung adenocarcinoma CTC line CTC-TJH-01, we performed transcriptome analysis to identify differentially expressed genes. CCK-8, LDH, Calcein AM/EthD-1, and Annexin V-FITC/caspase-3 assays evaluated the effects of osimertinib, Tivantinib, or their combination on CTC-TJH-01 and A549 cell proliferation and apoptosis. RT-qPCR, western blot, and immunohistochemistry analyzed gene and protein expression. A lung metastasis mouse model was established by injecting CTC-TJH-01 clusters, with anatomical observation and H&E staining for evaluation. RESULTS: Our study demonstrated that CTC-TJH-01, A549, and H1975 cell clusters in suspension exhibited higher resistance to osimertinib compared to their adherent counterparts. Notably, the expression of the HGF gene was remarkably upregulated in CTC-TJH-01 cell clusters. Activation of the HGF/c-MET pathway was observed in CTC clusters, accompanied by a concurrent downregulation of EGFR protein expression. Significantly, the c-MET inhibitor Tivantinib, but not the HGF inhibitor SRI, effectively suppressed the survival of CTC-TJH-01 and A549 cell clusters. Moreover, Tivantinib, either as a single-agent or in combination with osimertinib, exerted a potent inhibitory effect on the in vivo metastasis of CTC-TJH-01 cell clusters. CONCLUSION: These findings indicate that CTC clusters contribute to resistance against EGFR-TKI treatment, and c-MET inhibitors hold promise as potential therapeutic agents for targeting CTC cluster survival to impede lung cancer metastasis.

Symptom clusters are closely related to the decline in patients’ quality of life, increased risk of treatment interruption and poor prognosis. Among patients with ovarian cancer, the manifestation of psychoneurological symptom clusters are particularly prominent, seriously affecting their quality of life and prognosis of the disease. Efficient intervention measures are urgently needed. However, there is still a lack of specific treatment methods for the psychoneurological symptom clusters of ovarian cancer at present. Traditional Chinese medicine shows great potential in improving tumor-related symptom clusters and has unique advantages in overall regulation and comprehensive intervention. The primary objective of this study is to evaluate the efficacy and safety of the TSZA regimen in alleviating mental and psychological symptoms among ovarian cancer patients. Secondary objectives include assessing its impact on patients’ quality of life and survival outcomes. Furthermore, the study aims to explore the characteristics of the patient population that derives benefit from the TSZA regimen for these symptoms. A total of 316 ovarian cancer patients aged 18 to 70 with psychoneurological symptom cluster will be included and randomly divided into two parallel groups. Both groups will receive standard treatment for ovarian cancer as the basic treatment. The experimental group will receive the TSZA regimen, that is, Compound Ciwujia Granules (containing Acanthopanax senticosus and Schisandra chinensis) combined with psychological intervention. The control group will receive placebo combined with psychological intervention. The primary outcome measure is the psychoneurological symptom cluster score. Secondary outcome measures included the Pittsburgh Sleep Quality Index (PSQI), the Patient Health Questionnaire -9 (PHQ-9), the Generalized Anxiety Disorder -7 (GAD-7) scale, the revised Piper Fatigue Scale, the EORTC QLQ-C30 Quality of Life Scale, the TCM Syndrome Scale, and the 1-year survival analysis. In addition, this study also set a series of exploratory indicators (including sleep diary, functional magnetic resonance imaging, biomarkers of peripheral blood and tumor tissue, proportion of immune cells, cytokine levels, HPA axis function and immune gene expression analysis) and safety indicators (including vital signs, liver and kidney function and electrocardiogram). The study will be evaluated based on different indicators during the treatment period (baseline and the 1st, 2nd, and 3rd months of enrollment) and the follow-up period (the 6th, 9th, and 12th months of enrollment). Data analysis will be conducted using SPSS 26 software. A p value <0.05 is considered statistically significant. This study is designed to enroll a total of 316 participants. Participant enrollment is set to commence in October 2025, with no recruitment having occurred as of November 2025. The recruitment period will extend until September 2028 or until the target enrollment is met. Data analysis is scheduled for November 2028, with submission of the trial results to a peer-reviewed journal anticipated by May 2029. This study will evaluate the efficacy of the TSZA regimen in managing psychoneurological symptom clusters in ovarian cancer patients, and generate clinical evidence for a new therapeutic option that improves quality of life and alleviates the symptom burden. ClinicalTrials.gov NCT07050563; https://clinicaltrials.gov/study/NCT07050563

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.

ETHNOPHARMACOLOGICAL RELEVANCE:Metastasis is the leading cause of death in lung cancer worldwide, and immune escape plays a vital role in the process of metastasis. Clinical studies have proven that Jinfukang (JFK) can effectively treat lung cancer metastasis by regulating T lymphocytes. However, it is still unknown whether JFK plays a role in treating lung cancer metastasis by regulating T-cell receptors (TCRs).AIM OF THE STUDY:To explore the effect of JFK in inhibiting lung cancer metastasis by regulating TCR.MATERIALS AND METHODS:A lung metastasis model was established in C57BL/6J and BALB/c-nude mice by tail vein injection of Lewis lung cancer cells. JFK was given by continuous intragastric administration. Anatomical observation combined with hematoxylin-eosin staining was used to evaluate lung metastasis. T cells, MDSCs, and macrophages in the peripheral blood were detected by flow cytometry, and the proliferation and immune cell infiltration of lung metastases were observed by immunohistochemistry and immunofluorescence. The diversity and gene expression of TCR in peripheral blood and lung tissues were detected by immune repertoire sequencing, and bioinformatics analysis was carried out.RESULTS:Compared with the control group, the number of pulmonary metastatic nodules in JFK-treated mice showed a decreasing trend, and it significantly reduced the burden of lung tumor metastasis in mice. We found that the expression level of Ki-67 protein in lung metastatic tumor tissues of mice treated with JFK was significantly reduced, while the infiltration level of CD8+ T lymphocytes and NK cells was significantly increased. In addition, we also found that JFK could significantly increase the proportion of CD4+ T, CD8+ T and NKT cells in the peripheral blood of mice. Moreover, JFK reduced the ratio of M-MDSCs and increased the ratio of PMN-MDSCs in the peripheral blood of mice. JFK increased the ratio of M1 macrophages in the peripheral blood of Lewis tumor-bearing mice. The sequencing of TCR in the peripheral blood and lung tissue of mice indicated that there was no notable difference in TCR diversity as the tumor progressed and JFK treatment was administered. However, the downregulation of TRBV16, TRBV17, TRBV1 and the upregulation of the TRBV12-2 gene in the TCR caused by tumor progression can be reversed by JFK.CONCLUSION:These results suggest that JFK may upregulate the proportion of CD4+ T, CD8+ T and NKT cells in peripheral blood, reverse the TCR changes caused by tumor metastasis, and promote the infiltration of CD8+ T and NK cells in tumor tissues, thereby inhibiting the growth of tumors and ultimately reducing the burden of lung cancer metastasis. This will provide new strategies for developing Chinese herbal medicine to treat metastasis by regulating TCR.

Background:Colorectal cancer (CRC) is an insidious malignancy and the occurrence of chemotherapy resistance and toxicity seriously limits its clinical efficacy. Insect Compound Particle [Chong Yao Fu Fang (CYFF)] is a traditional Chinese medicine (TCM) compound based on the concepts of "invigorating spleen for strengthening vital qi" and "collateral disease theory". In long-term clinical application, it can reduce the toxicity of CRC chemotherapy and improve the anti-tumor effect. However, there is currently a lack of high-quality clinical evidence to prove the clinical efficacy and safety of CYFF in the treatment of CRC. Methods:We plan to include 262 patients with locally advanced stage III CRC who had undergone surgery and achieved R0 resection. These patients will be randomized into a CYFF group (treated with CYFF combined with chemotherapy) and a control group (treated with placebo plus chemotherapy) at a 1:1 ratio. The patients were routinely followed-up every 2 weeks within 2 months and every 4 weeks after 2 months after the treatment, every 3 months within 1 year, and every 6 months after 1 year. The primary endpoint is disease-free survival (DFS), defined as the time from random assignment to recurrence of primary CRC or death from any cause. The secondary endpoints include overall survival (OS) (defined as the time from randomization to death from any cause), safety [any adverse events (AEs)], and the Colorectal Cancer-Specific Quality of Life Questionnaire (QLQ-CR38) score. Conclusions:Compared with previous studies, our current study applies CYFF plus basic adjuvant chemotherapy, which is expected to achieve better efficacy and longer survival than standard chemotherapy, and reduce the toxic and side effects of chemotherapy, improve the safety of clinical treatment. In addition, our present study is the first clinical study to evaluate the safety and efficacy of CYFF in combination with chemotherapy in the treatment of stage III CRC after R0 resection. Trial Registration:This clinical trial has been registered in the Chinese Clinical Trial Registry (ChiCTR) (registration No. ChiCTR2000037568; August 28, 2020).

BackgroundNon-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes.MethodsHere, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes.ResultsOur study revealed that the proteome in exosomes from NSCLC patients with metastasis was distinctly different from that from healthy individuals. The former had larger diameters and lower concentrations of exosomes than the latter. Furthermore, among the 1220 identified exosomal proteins, we identified two distinct panels of biomarkers. The first panel of biomarkers (FGB, FGG, and VWF) showed potential for early NSCLC diagnosis and demonstrated a direct correlation with the survival duration of NSCLC patients. The second panel of biomarkers (CFHR5, C9, and MBL2) emerged as potential biomarkers for assessing NSCLC metastasis, of which CFHR5 alone was significantly associated with the overall survival of NSCLC patients.ConclusionsThese findings underscore the potential of plasma exosomal biomarkers for early NSCLC diagnosis and metastasis prediction. Notably, CFHR5 stands out as a promising prognostic indicator for NSCLC patients. The clinical utility of exosomal biomarkers offers the potential to enhance the management of NSCLC.

We aim to discuss the inflammatory-cancer transformation of pulmonary nodules and traditional Chinese medicine prevention and treatment strategies by reviewing the mechanism of pulmonary nodule development. The key to the inflammation-cancer transformation of pulmonary nodules is latent toxicity due to vital qi deficiency. Therefore, the important way to prevent the development of lung cancer is to support vital qi and expel pathogens. One proven case is provided.

消化系统肿瘤是中国常见的恶性肿瘤,由于目前治疗方法存在局限性,研究方向从单纯研究肿瘤细胞内部机制延伸至研究肿瘤微环境中的外泌体与免疫细胞之间的作用和关系.消化系统肿瘤微环境中的外泌体可以通过传递信号抑制免疫细胞的杀伤能力,促进肿瘤的发生、发展.肿瘤细胞通过释放外泌体传递信息,诱导巨噬细胞极化,抑制免疫细胞活性,促进肿瘤转移及免疫逃逸.该文综述了消化系统肿瘤源性外泌体在肿瘤微环境中对免疫细胞作用的研究进展.

目的 分析比较左右半结肠癌及直肠癌根治术后患者的生存预后差异及影响因素.方法 选取2004年1月—2016年12月于上海中医药大学附属市中医医院、上海市普陀区中心医院和复旦大学附属肿瘤医院肿瘤科收治的Ⅰ～Ⅲ期结直肠癌根治术后病例1028例,分为右半结肠癌组243例、左半结肠癌组339例和直肠癌组446例,对比3组无疾病生存期(DFS)、总生存期(OS)、复发转移率的差异及其影响生存预后因素.结果 右半结肠癌组、左半结肠癌组和直肠癌组的中位DFS分别为9.13、16.43和52.17个月,3组比较差异有统计学意义(χ2/P=167.362/0.000),中位OS分别为22.93、28.98和60.83个月,3组比较差异有统计学意义(χ2/P=122.748/0.000).复发转移率比较,右半结肠癌组>左半结肠癌组>直肠癌组(χ2/P=172.251/0.000).化疗和中药治疗是OS的保护因素,肿瘤部位是影响OS的危险因素,右半结肠癌影响总生存期的风险是直肠癌的2.004倍(95％CI 1.582～2.540),左半结肠癌影响OS的风险是直肠癌的1.379倍(95％CI 1.082～1.758).中药治疗是DFS的保护因素,肿瘤部位为右半结肠是影响DFS的危险因素[OR(95％CI)=0.794(0.655～0.961),1.365(1.098～1.698)].结论 直肠癌的生存预后明显优于结肠癌,相比左半结肠癌,右半结肠癌患者的生存期更短,复发转移率更高.中药治疗不仅能延长生存期,还能降低结直肠癌术后患者复发转移的风险.

目的 探究散结抑癌方联合贝伐珠单抗对BALB/c裸鼠结肠癌肺转移的影响,以及对血管内皮生长因子(VEGF)蛋白表达的影响.方法 采用经尾静脉注射对数生长期的人源结肠癌HCT116荧光细胞的方法,构建BALB/c裸鼠肺转移模型.将造模成功的20只裸鼠随机分为4组,每组5只.中药组,散结抑癌方灌胃;西药组,贝伐珠单抗腹腔注射;联合组,散结抑癌方灌胃+贝伐珠单抗腹腔注射;对照组,生理盐水灌胃.每周进行1次活体荧光成像观察肿瘤生长情况,记录小鼠体质量.干预4周后取小鼠肺组织,H-E染色观察小鼠结肠癌肺转移情况,免疫组织化学法检测VEGF蛋白表达情况.结果 与干预前比较,对照组在干预后体质量下降最多.干预后,中药组体质量略高于对照组(P>0.05),联合组体质量略高于西药组(P>0.05),联合组和西药组体质量均明显高于对照组(P<0.05).小动物成像定量分析结果显示,干预后中药组、西药组和联合组生物发光光子数均少于对照组(P均<0.05).H-E染色结果指出,对照组转移灶面积最大,转移处最多,联合组转移灶面积最小,转移处最少.免疫组织化学检测结果显示,对照组VEGF蛋白平均阳性细胞率为48.57％,高于中药组(39.91％)、西药组(35.82％)和联合组(29.03％),差异均有统计学意义(P均<0.01).结论 散结抑癌方可以抑制结肠癌肺转移,作用途径可能与VEGF蛋白表达相关.

Objective To analyze the active compounds, potential targets, and diseases of JianPi Fu Recipe (JPFR) based on network pharmacology and bioinformatics and verify the potential biological function and mechanism of JPFR in vitro and in vivo. Methods Network pharmacology databases including TCMSP, TCM-PTD, TCMID, and DrugBank were used to screen the active compounds and potential drug targets of JPFR. Cytoscape 3.7 software was applied to construct the interaction network between active compounds and potential targets. The DAVID online database analysis was performed to investigate the potential effective diseases and involved signaling pathways according to the results of the GO function and KEGG pathways enrichment analysis. To ensure standardization and maintain interbatch reliability of JPFR, High Performance Liquid Chromatography (HPLC) was used to establish a “chemical fingerprint.” For biological function validation, the effect of JPFR on the proliferation and migration of CRC cells in vitro was investigated by CCK-8 and transwell and wound healing assay, and the effect of JPFR on the growth and metastasis of CRC cells in vivo was detected by building a lung metastasis model in nude mice and in vivo imaging. For the potential mechanism validation, the expressions of MALAT1, PTBP-2, and β-catenin in CRC cells and transplanted CRC tumors were detected by real-time PCR, western blot, and immunohistochemical staining analysis. Results According to the rules of oral bioavailability (OB) > 30% and drug-likeness (DL) > 0.18, 244 effective compounds in JPFR were screened out, as well as the corresponding 132 potential drug targets. By the analysis of DAVID database, all these key targets were associated closely with the cancer diseases such as prostate cancer, colorectal cancer, bladder cancer, small cell lung cancer, pancreatic cancer, and hepatocellular carcinoma. In addition, multiple signaling pathways were closely related to JPFR, including p53, Wnt, PI3K-Akt, IL-17, HIF-1, p38-MAPK, NF-κB, PD-L1 expression and PD-1 checkpoint pathway, VEGF, JAK-STAT, and Hippo. The systematical analysis showed that various active compounds of JPFR were closely connected with Wnt/β-catenin, EGFR, HIF-1, TGFβ/Smads, and IL6-STAT3 signaling pathway, including kaempferol, isorhamnetin, calycosin, quercetin, medicarpin, phaseol, spinasterol, hederagenin, beta-sitosterol, wighteone, luteolin, and isotrifoliol. For in vitro experiments, the migration and growth of human CRC cells were inhibited by the JPFR extract in a dose-dependent way, and the expression of MALAT1, PTBP-2, β-catenin, MMP7, c-Myc, and Cyclin D1 in CRC cells were downregulated by the JPFR extract in a dose-dependent way. For in vivo metastasis experiments, the numbers of lung metastasis were found to be decreased by the JPFR extract in a dose-dependent manner, and the expressions of metastasis-associated genes including MALAT1, PTBP-2, β-catenin, and MMP7 in the lung metastases were downregulated dose dependently by the JPFR extract. For the orthotopic transplanted tumor experiments, the JPFR extract could inhibit the growth of orthotopic transplanted tumors and downregulate the expression of c-Myc and Cyclin D1 in a dose-dependent manner. Moreover, the JPFR extract could prolong the survival time of tumor-bearing mice in a dose-dependent manner. Conclusions Through effective network pharmacology analysis, we found that JPFR contains many effective compounds which may directly target cancer-associated signaling pathways. The in vitro and in vivo experiments further confirmed that JPFR could inhibit the growth and metastasis of CRC cells by regulating β-catenin signaling-associated genes or proteins.

新型冠状病毒肺炎(Novel coronavirus pneumonia,简称COVID-19)是指由新型冠状病毒(简称2019-nCoV)引起的以发热、咳嗽、头痛、乏力、呼吸困难等症状为主要临床表现的病毒型肺炎.我国最早的COVID-19患者被发现于武汉,患者从感染到发病通常在14天内,该病毒具有较强的传染性.截止至2020年2月23日,COVID-19患者累计77049例,导致不少于2445位患者死亡.与SARS相比,COVID-19进展快,危重患者多存在肺损伤、肝功能异常、急性呼吸窘迫综合征,最终发展至多器官衰竭、休克.危重COVID-19患者的病理变化机制目前仍未阐释清楚,有学者从COVID-19引起的炎症瀑布揭示COVID-19患者肝功能异常.COVID-19病理发展变化最终需要详实的解剖和病理研究证实.COVID-19给我国造成的危害不亚于2003年我国爆发的SARS.在当前COVID-19防治工作中,仍未形成全球公认最佳疗效的治疗指南,现代医学与传统医学救治措施均有报道.本文将COVID-19的最新中西医防治方法和措施予以汇总,为COVID-19防治工作提供支持.

"络病学说"作为重要的中医基础病机之一,近年来被广泛应用于肿瘤类疾病的临床诊疗中,其对于肿瘤的发生发展以及转移等机制研究与治疗均有理论指导意义."络病"在形态与功能上与现代医学中的肿瘤微血管、微循环概念相似;瘀阻络脉与肿瘤患者血液高凝状态类似,故运用"通络法"抗肿瘤具有充足的理论依据.虫类药是动物药的别称,作为通络药的代表,善于搜刮剔络,在肿瘤的防治中起到了活血化瘀通络、攻毒散结通络、搜风解毒通络以及补益培本通络等作用.通过梳理"络病学说"的起源、发展与成熟阶段的主要思想内涵,整理并总结现代肿瘤治疗中"络病学说"的相关研究与应用,并分析虫类药在通络法中的具体应用,以期为开展中医络病防治肿瘤的临床应用提供理论依据.

消化系统肿瘤的发生是由多种因素引起的抑癌基因或促癌基因发生突变所导致的.NF2基因是一种抑癌因子,其编码Merlin蛋白功能的缺失是造成消化系统肿瘤发生、发展的重要因素.NF2/Merlin通过Hippo/Yap、Wnt/β-catenin、转化生长因子-β(TGF-β)等多条信号通路发挥抗肿瘤作用.该文综述了NF2基因及其表达产物Merlin蛋白在消化系统肿瘤发生、发展过程中的抑制作用,旨在为探究NF2/Merlin的抑癌机制及肿瘤防治方法提供新思路.