Germline mutations were evaluated in 530 Chinese breast cancer (BC) patients with different HER2 expression status plus 98 patients with atypical ductal hyperplasia or a breast cancer family history. DNA extracted from blood samples was analyzed with a next generation sequencing based multigene panel, with reporting of likely pathogenic and pathogenic variants (PV) of 102 cancer associated genes, and correlation between clinicopathologic characteristics and known BC-associated genes. The 71 identified PVs were categorized into five distinct pathway clusters: BRCA/FANC, DDR, HRR, FANC, and Other. The distribution of PVs enriched within these clusters differed significantly between BC patients and unaffected individuals (p = 0.031). This difference was primarily driven by the BRCA/FANC, FANC, and DDR clusters, with enrichment percentages of 57.7

BackgroundAlthough next-generation sequencing (NGS) has been widely used to provide comprehensive somatic mutational information for individualized therapy in breast cancer patients, whether or not it could reliably evaluate HER2 status to guide targeted therapy when compared to the current IHC/FISH standard criteria still lacks sufficient validations.MethodsWe analyzed the clinicopathological and NGS somatic genomic data of 1,171 Chinese breast cancer patients. A commercial 520 gene panel was used to generate genomic variation data by NGS in breast cancer samples. We compared the concordance of HER2 status between NGS evaluation and IHC/FISH criteria. We further defined the amplification status of HER2 based on the length of amplification region beginning from ERBB2 and extending to adjacent genes by focal (<1 megabase) versus broad (>1 megabase) amplification and stratified the cohort accordingly to investigate its potential in predicting efficacy of trastuzumab-based neoadjuvant therapy.ResultsNGS showed high concordance with FISH/IHC-defined HER2 status with a sensitivity of 95.7%, specificity of 94.2%, and overall concordance rate of 94.9%. NGS characterized the genomic landscape of enrolled patients, identifying frequent mutations including TP53, ERBB2, PIK3CA, CDK12, MYC, and CCND1. The focal amplification subgroup exhibited significantly higher gene copy number (GCN) (31.7 vs 10.2, p < 0.001), greater HER2 positivity rates (98.3% vs. 78.3%, p < 0.001), higher IHC 3+ prevalence (91.7% vs. 48.5%, p < 0.001) and increased FISH + proportion (98.5% vs. 77.9%, p < 0.001). In patients receiving HER2-targeted neoadjuvant therapy, the focal amplification group had a higher pCR rate compared with broad amplification group (46.0% vs. 20.0%, p = 0.031).ConclusionNGS demonstrates comparable capability to IHC/FISH in HER2 status interpretation and provides additional genomic information. Higher HER2 NGS copy numbers and focal amplification may be associated with a higher pCR rate.

Background Diabetic cardiomyopathy (DCM), a consequential cardiovascular complication of diabetes mellitus, drives progressive myocardial fibrosis and cardiac dysfunction, culminating in heart failure (HF). Ginsenoside Rc (Rc) has significant antidiabetic and cardiovascular protective properties, but its potential to improve DCM is unclear. Purpose The aim of this study was to explore the mechanism of Rc against DCM. Methods The DCM model was established in db/db mice to evaluate the effects of Rc on metabolic and adipokine indicators in serum, and echocardiography and histological examinations were used to detect cardiac function in the mice. A lipotoxicity model of H9c2 cells was established using PA to verify the protective effect of Rc on cardiomyocytes, reduce lipotoxicity and improve mitochondrial function. The effect of Rc on adiponectin (APN) was demonstrated in 3T3 - L1 cells. Lipid metabolomics was used to explore the possible pathways by which Rc improves DCM. Quantitative reverse transcription polymerase chain reaction (qRT‒PCR) and western blot (WB) were used to detect gene and protein expression in mouse hearts and H9c2 cells. Results Rc reduced body weight, glycemia, dyslipidemia, and inflammatory mediator levels in db/db mice. It alleviated myocardial fibrosis and lipid accumulation and protected against lipotoxicity-induced damage in H9c2 cells. Furthermore, Rc enhanced mitochondrial function in lipotoxic H9c2 cells while suppressing reactive oxygen species (ROS) generation. Rc also reduced hepatic lipid accumulation in db/db mice while decreasing lipid droplet accumulation in 3T3-L1 cells. Critically, Rc elevated circulating APN levels in both db/db mice and 3T3-L1 cells, which increased the expression of APPL1, LKB1 and AdipoR1 in both the hearts of db/db mice and lipotoxicity-induced H9c2 cells. Lipid metabolomics analysis of db/db mouse serum and urine revealed that Rc primarily regulated autophagy-related pathways. Rc significantly increased the number of autophagic vesicles in H9c2 cells with lipotoxicity and promoted autophagy pathways in both the hearts of db/db mice and lipotoxic H9c2 cells. This increased AMPKα2 phosphorylation, Beclin1 expression and the LC3II/LC3I ratio while reducing p62 expression. Conclusion Collectively, these data indicated that Rc could rectify glucose/lipid metabolic perturbations, attenuate oxidative stress and inflammation, and restore mitochondrial functionality. Rc promoted APN secretion and activated the AdipoR1/APPL1/LKB1/AMPKα2 signaling pathway, further enhancing autophagy, increasing the ratio of LC3II/LC3Ⅰ and the expression of Beclin1, and decreasing the expression of p62, which reduced lipotoxicity and demonstrated potential for preventing and treating DCM.

Manipulation of polar functional groups to extend the druggability and developability space is an important approach in the current field of drug discovery. Here, we report an editing method that enables the direct insertion of anthranilyl units into inert amides to form versatile oligoamides and cyclic peptides under exceptionally mild reaction conditions. We showcase a diverse array of pharmaceuticals, natural products, and bioactive molecules involving the mentioned scaffold insertion. The synthesis of the secondary metabolites from marine-derived fungi, the expedited construction of bioactive molecules, and the assembly of functionalized peptide macrocycles through iterative insertions highlight the synthetic utility of this method. Computational tools and experimental measurements indicate that a hydrogen bond network formed by reacting and catalytic amide enables the insertion of the anthranilyl unit into a C─N bond.

Introduction Ischemic stroke severely threatens human health. Rapid restoration of cerebral blood flow (CBF) in ischemic microvessels is significant as it enhances neurovascular function, prevents neuronal death, and minimises cerebrovascular injury. Although butylphthalide (NBP) is commonly used to treat ischemic stroke, its exact molecular target remains unclear. Objective Our research aims to explore NBP’s molecular target and mechanism in ischemic stroke treatment, providing more evidence for its clinical application. Methods We confirmed NBP’s protective effect on the neurovascular network by performing MCAO/R surgery on rats and using immunofluorescence and optical coherence tomography angiography for monitoring. We then employed photoaffinity labeling click chemistry for activity-based protein profiling (PAL-CC-ABPP) to identify the NBP’s target protein. Molecular docking and dynamics simulations were conducted to investigate NBP-protein interactions. Additionally, we examined the effect of VIM knockdown in vascular endothelium and neurons on cerebral microvessels. The Notch pathway was explored to understand the mechanism of NBP-induced post-stroke neovascularization and neurorestoration. Results Our research demonstrated that NBP can enhance CBF, increase microvessel density in the ischemic brains of rats, repair microvascular injuries and foster neurological recovery. Through PAL-CC-ABPP, vimentin (VIM) was identified as the target protein of NBP. And NBP could provide protective effects by targeting the amino acid residue Arg-304 in VIM’s active site. Furthermore, our findings indicate that VIM knockdown within the vascular endothelium interferes with properly forming cerebral microvessels and neurons. In contrast, VIM knockdown in neurons primarily impacts electrical signals and brain development, rather than angiogenesis. This suggests that VIM in blood vessels is crucial in maintaining the neurovascular network. Additionally, NBP enhances post-stroke neovascularization and neurorestoration by targeting VIM, which affects the Notch pathway. Conclusion Our study reveals NBP can effectively treat ischemic stroke by targeting VIM to revitalise microvasculature, facilitating neurorestoration.

Alternative splicing (AS) is the central mechanism of transcriptional regulation and generates diverse splice variants that influence protein structure, function, and intracellular activity. AS plays critical roles in tissue differentiation, organ development, and disease progression. This review focuses on the pivotal roles of AS in bone biology, highlighting its regulatory effects on osteoblasts, osteoclasts, chondrocytes, bone matrix remodeling, and bone remodeling, as well as the involvement of AS-related RNA-binding proteins in these processes. We also emphasize bone-specific AS events and their physiological importance in skeletal development and maintenance. Furthermore, the pathological role of AS is emphasized in bone-related tumors such as osteosarcoma, Ewing sarcoma, and chondrosarcoma. This review also explores aberrant AS mechanisms in bone metastatic cancers, including prostate, bladder, and breast cancers, with an in-depth analysis of their roles in tumor progression and alterations in the bone microenvironment. This review provides a comprehensive perspective on how AS factors, signaling pathways, and mechanical stimulation collaboratively regulate bone cells under both physiological and pathological conditions, paving the way for identifying potential intervention strategies. The mechanisms of AS in other pathological bone conditions, such as osteoporosis, osteoarthritis, and hereditary bone disorders, are also summarized. The potential applications of targeting AS in the diagnosis and treatment of bone diseases are discussed, offering insights into the underlying mechanisms and clinical translational potential.

Near -infrared two -region (NIR-II, 1000-1700 nm) fluorescence imaging has received widespread attention because of its high in vivo penetration depth, high imaging resolution, fast imaging speed and high efficiency, dynamic imaging, and high clinical translatability. This paper reviews the application of NIR-II imaging technology in disease diagnosis and treatment. The paper highlights the latest research progress of commonly used NIR-II imaging materials and the latest progress of multifunctional diagnostic platforms based on NIR-II imaging technology, and discusses the challenges and directions for the development and utilization of novel NIR-II imaging probes.

Background Ischemic stroke is a devastating disease that can result in permanent disability and death, and angiogenesis plays a critical role in the recovery and survival of patients and animal models of ischemic stroke. Panax notoginseng has been used as a key herb in the treatment of stroke diseases due to its effect in promoting blood circulation and removing blood stasis. However, the role of Panax notoginseng saponins, in promoting angiogenesis is unclear. Purpose This study is aimed to investigate the effect of Xueshuantong (XST) injection, composed of Panax notoginseng saponins in post-stroke revascularization. Method In the present study, a middle cerebral artery occlusion/reperfusion model was established in Sprague-Dawley rats, with XST and the positive drug Dl-3-n-butylphthalide (NBP) administered via intraperitoneal injection to observe vascular changes after stroke. The protective and pro-angiogenic effects of XST after stroke were demonstrated by Triphenyltetrazolium chloride staining and optical coherence tomography angiography. Subsequently, network pharmacology and molecular docking techniques, as well as in vitro experimental validation, were used to further analyze the potential mechanism by which XST promotes angiogenesis. Results The results showed that XST could reduce the cerebral infarction region in rats. And the neovascularization in the ischemic area of the rat brain significantly increased after 7 or 14 days of XST administration. Furthermore, XST could activate the vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2), and hypoxia-inducible factor 1 (HIF-1) signaling pathways. Conclusion XST may promote post-stroke angiogenesis by affecting the HIF1-α/VEGFA/VEGFR2 signaling pathways.

[This corrects the article DOI: 10.1016/j.jgr.2024.08.004.].

Abstract Background: Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer (BC) is associated with lower survival and higher risk of disease recurrence. A new subtype of HER2-low BC which has been proposed from several studies demonstrates that HER2-low patients have distinct somatically genetic alterations and clinical outcomes. We have previously reported that HER2-low BC had distinct clinical and somatic mutational feature compared with HER2-zero and HER2-high tumors. We have therefore extended studies by comparing germline mutation expression among these HER2 subgroups. Methods: 530 Chinese women with BC were enrolled in a prospective protocol between May 2021 to March 2023 at Guangdong Provincial People's Hospital. Genomics data was generated from a gene panel that surveys 102 tumor mutations. Germline variants were classified into pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign (LB) and benign (B) groups according to the ACMG/AMP Standards and Guidelines. The cohort was divided into three groups based on HER2 status as HER2-zero (n = 107), HER2-low (n = 259), and HER2-high (n = 127) according to immunohistochemistry and/or fluorescence in situ hybridization results. Results: The most common mutated genes were ATM, FANCD2, ATR, BRACA2, RECQL4 and APC. A total of 71 pathogenic or likely pathogenic (P/LP) mutations were identified in 25 cancer susceptibility genes from 64 patients (12.16%). The most frequent mutated P/LP genes are BRCA2, BRCA1, PALB2, PMS2, MUTYH and PTEN in the HER2-low group; BRCA2, BRCA1 and PALB2 in the HER2-zero cohort; Interestingly, among the nine HER2-high patients, we detected unique P/LP genes in each sample including MRE11, FANCM, ATM, FLCN, NTRK1, TP53, BRCA1, CHEKE2 and FANCA. In addition to P/LP mutations, 751 variants of uncertain significance (VUS) in 95 cancer susceptibility genes were also detected in 361 patients (68.11%). The most frequent mutated VUS mutations occurred genes are FANCD2, ATM, RECQL4, RAD54B and ATR in HER2-low group; ATM, FANCA, POLE, MSH2 and FANCD2 in HER2-zero cohort; and ATM, BRCA2, RECQL4, POLE, FANCI and FANCM for HER2-high patients. Most of mutated genes were homologous recombination repair (HRR) or DNA damage repair (DDR) pathway related genes. Several genes were differentially altered across HER2 subgroups, including the mutation frequency of the BMPR1A (p=0.0344), MSH2 (p=0.0103), and RAD51C (p=0.0336) genes that were significantly higher in HER2-zero group. It’s worth noting that RAD51C was only mutated in HER2-zero subgroup. BMPR1A and MSH2 were also mutated in HER2-low patients. Differentially mutated genes in specific HER2 subgroups may contribute to better research and choice of future therapeutic approaches. In 115 patients who received neoadjuvant therapy and 84 of them were evaluable for pathological response data, HER2-low patients had lower pathological complete response (pCR) rates than HER2-zero and HER2-high subgroups (p=0.0008). In particular, DDR pathway gene ERCC1 have significantly higher mutation frequency in pCR patients (p=0.0115). Conclusion: HER2-low BC patients have distinct germline mutational signatures and differential clinical outcomes under neoadjuvant systemic therapy. These results have provided additional evidence that HER2-low patients comprise a fourth subtype of BC that needs to be accounted for separately in terms of clinical treatment and outcome reporting. Keywords: breast cancer, germline mutations, human epidermal growth factor receptor 2 (HER2), HER2-low, targeted therapy, next-generation sequencing Table 1. List of most frequent mutated genes in HER2-zero, HER2-low and HER2-high groups Citation Format: Ning Liao, Weiqi Zhang, Liangqiu Liu, Wendy Wu, Siqi Wang, Li Cao, Jianguo Lai, Xueying Zhang, Airong Yang, Yulei Wang, Cheukfai Li, Guochun Zhang, Chongyang Ren, Lingzhu Wen. Unique molecular signatures of germline mutations in low expression of human epidermal growth factor receptor 2 (HER2) breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-09.

Learning and memory disorder is a cluster of symptoms caused by neuronal aging and other diseases of the central nervous system (CNS). Panax notoginseng saponins (PNS) are a series of saponins derived from the natural active ingredients of traditional Chinese medicine (TCM) that have neuroprotective effects on the central nervous system. In this paper, we review the ameliorative effects and mechanisms of Panax notoginseng saponin-like components on learning and memory disorders to provide valuable references and insights for the development of new drugs for the treatment of learning and memory disorders. Our summary results suggest that Panax ginseng saponins have significant effects on improving learning and memory disorders, and these effects and potential mechanisms are mediated by their anti-inflammatory, anti-apoptotic, antioxidant, β-amyloid lowering, mitochondrial homeostasis in vivo, neuronal structure and function improving, neurogenesis promoting, neurotransmitter release regulating, and probiotic homeostasis in vivo activities. These findings suggest the potential of Panax notoginseng saponin-like constituents as drug candidates for improving learning and memory disorders.

BAP1-UCH, BAP1-ULD, and ASXL2-AB form a ternary stable protein complex in vitro. Gel filtration analysis of highly purified recombinant BAP1-UCH, BAP1-ULD and ASXL2-AB, and a pre-formed UCH-ULD-AB complex. The proteins were resolved on a Superdex 200 column. The fractions were collected, and the proteins were analyzed by NuPAGE. The fraction numbers are labeled at the top of the figure. The migration of protein standards is indicated above the gels. The protein standards were in a parallel gel filtration experiment under identical conditions: (I) the elution profile of for a pre-formed UCH-ULD-AB complex; (II) the elution profile of UCH; (III) the elution profile of the AB box; and (IV) the elution profile of ULD.

The deletion R666-H669 in the ULD domain of BAP1 corresponding to that observed in a uveal melanoma completely abolished ASXL2 binding in vivo. HEK 293 cells were co-transiently transfected with plasmids expressing WT or mutant BAP1 and ASXL2 (261-649aa) proteins. At 48 h post-transfection, the cells were collected and whole cell lysates were used for co-IP with ANTI-Flag M2 Affinity Gel. Western blot analyses were performed with BAP1 (rAb) and Flag (rAb).

Background: Germline DNA damage repair (DDR) mutations has been associated with increased cancer risk, PARP inhibitor therapeutic opportunity for breast cancer (BC) patients. However, the profile of germline mutations in BC covering comprehensive DDR genes remains unclear. Methods: A total of 341 women with breast cancer who tested 102 germline related genes (including 50 DDR genes) between April 2021 to May 2022 in Guangdong Provincial People’s Hospital were identified. Variants were classified into pathogenic, likely pathogenic, variant of uncertain significance (VUS), likely benign and benign groups according to the ACMG/AMP Standards and Guidelines. We defined pathogenic and likely pathogenic variants as deleterious mutations. Results: The median age of 341 breast cancer patients was 48 (range, 20-89) at the first diagnosis of BC. A total of 47 patients (13.78%) carried 53 deleterious germline variants in 21 cancer predisposition genes, 16 of which were DDR genes. DDR deleterious mutations were detected in genes including BRCA2 (n=18), BRCA1(n=7), FANCA (n=4), PMS2 (n=4), PALB2(n=2), RECQL4(n=2), PALB2 (n=2), etc. The younger age at diagnosis (less than 40-year-old) were significantly associated with deleterious mutations in DDR pathway(P=0.02). At least one VUS was identified in 238 (69.79%) patients. The top 5 DDR VUS genes were FANCM (n=21), ATM (n=20), RAD54L (n=17), FANCD2 (n=15) and ATR (n=14). Breast or ovarian cancer family history were significantly correlated with VUS germline mutations in DDR pathway(P=0.039). Interesting, we found that patients with pCR efficacy of neoadjuvant therapy were more likely to have VUS mutations in DDR pathway (table 1). Conclusion: We provided a comprehensive view of germline DDR gene mutations in BC patients and also analyzed the association between clinical characteristics and germline DDR mutation status. DDR mutations are prevalent in Chinese BC patients. Patients with younger and breast or ovarian cancer family history were more likely to carry DDR alterations. Moreover, patients with higher frequency of DDR VUS mutations may benefit from neoadjuvant therapy. Table 1. Clinicopathological characteristics between germline mutation carriers and non-carriers Citation Format: Ning Liao, Li Cao, Guochun Zhang, Junyun Wang, Airong Yang, Yulei Wang, Kai Li, Lingzhu Wen, Chongyang Ren, Minghan Jia, Cheukfai Li, Hsiaopei Mok, Bo Chen, Jianguo Lai, Weikai Xiao. Comprehensive analysis of DNA damage repair gene germline mutations in Chinese breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-12-06.

Supplemental figure legends

Lifestyle changes have led to increased incidence of cardiovascular disease (CVD); therefore, potential targets against CVD should be explored to mitigate its risks. Adiponectin (APN), an adipokine secreted by adipose tissue, has numerous beneficial effects against CVD related to glucose and lipid metabolism disorders, including regulation of glucose and lipid metabolism, increasing insulin sensitivity, reduction of oxidative stress and inflammation, protection of myocardial cells, and improvement in endothelial cell function. These effects demonstrate the anti-atherosclerotic and antihypertensive properties of APN, which could aid in improving myocardial hypertrophy, and reducing myocardial ischemia/reperfusion (MI/R) injury and myocardial infarction. APN can also be used for diagnosing and predicting heart failure. This review summarizes and discusses the role of APN in the treatment of CVD related to glucose and lipid metabolism disorders, and explores future APN research directions and clinical application prospects. Future studies should elucidate the signaling pathway network of APN cardiovascular protective effects, which will facilitate clinical trials targeting APN for CVD treatment in a clinical setting.

BackgroudThere were limitations existing in programmed cell-death ligand 1 (PD-L1) as predictive biomarkers for breast cancer (BC), hence exploring the correlation between PD-L1 levels and other biomarkers in BC may become a very useful therapeutic clinical tool. MethodsA total of 301 Chinese patients with different BC subtypes including 47 HR+/HER2+, 185 HR+/HER2-, 38 HR-/HER2+, and 31 triple-negative breast cancer (TNBC) were enrolled in our study. Next-generation sequencing based Yuansu450 gene panel was used for genomic alteration identification and PD-L1 expression was tested using immunohistochemistry. ResultsThe most prevalent BC-related mutations were TP53 mutations, followed by mutations in PIK3CA, ERBB2, CDK12, and GATA3 in our Chinese cohort. We found that mutations DDR2 and MYCL were only mutated in HR-/HER2+ subtype, whereas H3-3A and NRAS mutations were only occurred in HR-/HER2- subtype. The percentage of patients with PD-L1-positive expression was higher in patients with HR-/HER2- mainly due to the percentage of PD-L1-high level. Mutational frequencies of TP53, MYC, FAT4, PBRM1, PREX2 were observed to have significant differences among patients with different BC subtypes based on PD-L1 levels. Moreover, a positive correlation was observed between TMB and PD-L1 level in HR+/HER2- subtype, and showed that the proportion of patients with high PD-L1 expression was higher than that of patients with low PD-L1 expression in the HR+/HER2- and HR+/HER2+ cohorts with high Ki67 expression. ConclusionsThe genomic alterations based on PD-L1 and other biomarkers of different cohorts may provide more possibilities for the treatment of BC with different subtypes.

Objective:To investigate the effects of ribonucleic acid for injection Ⅱ, often called RNA Ⅱ for short, combined with chemotherapeutic drug cyclophosphamide (CTX) on the tumor inhibition and survival of sarcoma cell S180 tumor-bearing mice.Methods:The solid transplanted tumor mouse model of sarcoma cell S180 and peritoneal fluid tumor mouse model were established respectively. CTX (25 mg/kg, once for 2 days) alone or combined with low-dose (25 mg/kg, once a day) and medium-dose (50 mg/kg, once a day) RNA Ⅱ were injected intraperitoneally into solid transplanted tumor mice for 10 d. CTX (25 mg/kg, once for 2 days) alone, medium-dose (50 mg/kg, once a day) or high-dose (100 mg/kg, once a day) RNA Ⅱ alone or combined with CTX were injected intraperitoneally into peritoneal effusion tumor mice until all mice died. The two models were set up for modeling groups without drug treatment, 8 mice in each group. The body mass of solid transplanted tumor mice after administration was weighed, the tumor tissue in vivo was taken out and weighed after the mice were executed, and the tumor inhibition rate was calculated. The body mass of peritoneal effusion tumor mice after administration was weighed, the growth rate of body mass was calculated, the survival curve of each group was drawn, and the life extension rate was calculated.Results:(1) Solid transplanted tumor mice: the body mass of mice in each administration group was lower than that in the modeling group after administration. During the administration period, the tumor volume in the modeling group was much higher than that in each administration group. From the 8th day of administration, the tumor volume in vivo in the CTX group began to be larger compared with that in the two combined administration groups. After stopping the administration and killing the mice, the weighing showed that the tumor mass of each administration group was lower than that in the modeling group (all P < 0.01), the tumor mass of CTX + RNA Ⅱ low-dose group and CTX + RNA Ⅱ medium-dose group was lower than that of CTX group (all P < 0.05), and the tumor inhibition rate of the two groups was higher than that of CTX group (83.6%, 77.2% vs. 58.5%). (2) Peritoneal effusion tumor mice: after administration for 12 d, the body mass growth rate of mice in CTX group was increased rapidly and reached the highest, and the body mass growth rate of mice in the two combined administration groups was lower than that in other groups. The life prolongation rates of RNA Ⅱ high-dose group and CTX group were 48.2% and 53.2% respectively, which had the same effect on life prolongation. The life prolongation rate in RNA Ⅱ medium-dose group was 20.9%. The life prolongation rates of CTX + RNA Ⅱ medium-dose group and CTX + RNA Ⅱ high-dose group were 94.2% and 105.0% respectively. Conclusions:RNA Ⅱ combined with CTX can significantly prolong the survival time of sarcoma cell S180 tumor-bearing mice, increase the tumor inhibition rate and improve the quality of life of the mice. Both of them have a synergistic effect.