Targeting SMYD2 promotes ferroptosis and impacts the progression of pancreatic cancer through the c-Myc/NCOA4 axis-mediated ferritinophagy.

BACKGROUND: Pancreatic cancer (PC) is characterized by a poor prognosis and limited treatment options. Ferroptosis plays an important role in cancer, SET and MYND domain-containing protein 2 (SMYD2) is widely expressed in various cancers. However, the role of SMYD2 in regulating ferroptosis in PC remains unexplored. This study aimed to investigate the role of SMYD2 in mediating ferroptosis and its mechanistic implications in PC progression. METHODS: The levels of SMYD2, c-Myc, and NCOA4 were assessed in PC tissues, and peritumoral tissues. SMYD2 expression was further analyzed in human PC cell lines. In BxPC3 cells, the expression of c-Myc, NCOA4, autophagy-related proteins, and mitochondrial morphology, was evaluated following transfection with si-SMYD2 and treatment with autophagy inhibitors and ferroptosis inhibitors. Ferroptosis levels were quantified using flow cytometry and ELISA assays. RNA immunoprecipitation was conducted to elucidate the interaction between c-Myc and NCOA4 mRNA. A xenograft mouse model was constructed to validate the impact of SMYD2 knockdown on PC growth. RESULTS: SMYD2 and c-Myc were found to be highly expressed in PC tissues, while NCOA4 showed reduced expression. Among the PC cell lines studied, BxPC3 cells exhibited the highest SMYD2 expression. SMYD2 knockdown led to decreased c-Myc levels, increased NCOA4 expression, reduced autophagy-related protein expression, mitochondrial shrinkage, and heightened ferroptosis levels. Additionally, an interaction between c-Myc and NCOA4 was identified. In vivo, SMYD2 knockdown inhibited tumor growth. CONCLUSIONS: Targeting SMYD2 inhibits PC progression by promoting ferritinophagy-dependent ferroptosis through the c-Myc/NCOA4 axis. These findings provide insights into potential diagnostic and therapeutic strategies for PC.

Role of the intratumoral microbiome in tumor progression and therapeutics implications.

Microbes are widely present in various organs of the human body and play important roles in numerous physiological and pathological processes. Nevertheless, owing to multiple limiting factors, such as contamination and low biomass, the current understanding of the intratumoral microbiome is limited. The intratumoral microbiome exerts tumor-promoting or tumor-suppressive effects by engaging in metabolic reactions within the body, regulating signaling cancer-related pathways, and impacting both host cells function and immune system. It is important to emphasize that intratumoral microbes exhibit substantial heterogeneity in terms of composition and abundance across various tumor types, thereby potentially influencing diverse aspects of tumorigenesis, progression, and metastasis. These findings suggest that intratumoral microbiome have great potential as diagnostic and prognostic biomarkers. By manipulating the intratumoral microbes to employ cancer therapy, the efficacy of chemotherapy or immunotherapy can be enhanced while minimizing adverse effects. In this review, we comprehensively describe the composition and function of the intratumoral microbiome in various human solid tumors. Combining recent advancements in research, we discuss the origins, mechanisms, and prospects of the clinical applications of intratumoral microbiome.

Chromosome-level Dinobdella ferox genome provided a molecular model for its specific parasitism.

BACKGROUND: Dinobdella ferox is the most frequently reported leech species parasitizing the mammalian nasal cavity. However, the molecular mechanism of this special parasitic behavior has remained largely unknown. METHODS: PacBio long-read sequencing, next-generation sequencing (NGS), and Hi-C sequencing were employed in this study to generate a novel genome of D. ferox, which was annotated with strong certainty using bioinformatics methods. The phylogenetic and genomic alterations of D. ferox were then studied extensively alongside the genomes of other closely related species. The obligatory parasitism mechanism of D. ferox was investigated using RNA-seq and proteomics data. RESULTS: PacBio long-read sequencing and NGS yielded an assembly of 228 Mb and contig N50 of 2.16 Mb. Along Hi-C sequencing, 96% of the sequences were anchored to nine linkage groups and a high-quality chromosome-level genome was generated. The completed genome included 19,242 protein-coding genes. For elucidating the molecular mechanism of nasal parasitism, transcriptome data were acquired from the digestive tract and front/rear ends of D. ferox. Examining secretory proteins in D. ferox saliva helped to identify intimate connections between these proteins and membrane proteins in nasal epithelial cells. These interacting proteins played important roles in extracellular matrix (ECM)-receptor interaction, tight junction, focal adhesion, and adherens junction. The interaction between D. ferox and mammalian nasal epithelial cells included three major steps of pattern recognition, mucin connection and breakdown, and repair of ECM. The remodeling of ECM between epithelial cells of the nasal mucosa and epithelial cells of D. ferox may produce a stable adhesion environment for parasitism. CONCLUSIONS: Our study represents the first-ever attempt to propose a molecular model for specific parasitism. This molecular model may serve as a practical reference for parasitism models of other species and a theoretical foundation for a molecular process of parasitism.

The characteristics of serum lipid spectrum in PanNENs and its correlation with clinicopathological features and prognosis.

Background: The role of dyslipidemia in pancreatic neuroendocrine tumors (PanNENs) is unclear. The aim of this study is to analyze the characteristics of serum lipid spectrum in PanNENs, and the effect of the variation in lipid profile on the development of PanNENs clinicopathological features and prognosis. Methods: All PanNENs patients between November 2012 and September 2020 in the authors' research center were identified from patient medical records and databases. A total of 185 with PanNENs patients were ultimately included in this study, including 100 nonfunctional PanNENs and 85 insulinomas. Clinicopathologic features, serum lipid level and overall survival results were retrospectively analyzed using statistical methods. Results: In 185 PanNENs, 95 (51.4%) patients appear to have dyslipidemia. Patients with insulinoma had a lower proportion of abnormal HDL than those with nonfunctional PanNENs (10.6% vs 23%, P=0.026). The mean serum HDL levels of insulinomas were 0.131 mmol/L higher than the NF-PanNENs (1.306 ± 0.324 vs 1.175 ± 0.315, P=0.006). In multivariate logistic analysis, high levels of HDL are negatively correlated to tumor size (OR 0.233, 95% CI: 0.069-0.790, P=0.019), but HDL was not associated with pathological grade or metastasis. And a correlation has been found between hypercholesterolemia and the original location of the tumor (OR:0.224, 95%CI: 0.066-0.753, P =0.016). In addition, the outcome of the survival analysis revealed that dyslipidemia did not influence the prognosis of PanNENs patients (P>0.05). Conclusions: HDL was negatively correlated with the tumor size of PanNENs. The serum HDL level of insulinoma patients is higher than nonfunctional PanNENs.

Impact of Individual Cell Parameter Difference on the Performance of Series-Parallel Battery Packs.

Lithium-ion power batteries are used in groups of series-parallel configurations. There are Ohmic resistance discrepancies, capacity disparities, and polarization differences between individual cells during discharge, preventing a single cell from reaching the lower limit of the terminal voltage simultaneously, resulting in low capacity and energy utilization. The effect of the parameter difference (difference in parameters) of individual cells on the performance of the series-parallel battery pack is simulated and analyzed by grouping cells with different parameters. The findings reveal that when cells are connected in series, the capacity difference is a significant factor impacting the battery pack's energy index, and the capacity difference and Ohmic resistance difference are significant variables affecting the battery pack's power index. When cells are connected in parallel, the difference in Ohmic internal resistance between them causes branch current imbalance, low energy utilization in some individual cells, and a sharp expansion of unbalanced current at the end of discharge, which is prone to overdischarge and shortens battery life. Interestingly, we found that when there is an aging cell in a series-parallel battery pack, the terminal voltage of the single battery module containing the aging single cell will decrease sharply at the end of discharge. Evaluating the change rate of battery module terminal voltage at the end of discharge can be used as a method to evaluate the aging degree of the battery module. The research results provide a reference for connecting batteries to battery packs, particularly the screening of retired power battery packs and the way to reconnect into battery packs.

Cancer-associated fibroblast-secreted miR-421 promotes pancreatic cancer by regulating the SIRT3/H3K9Ac/HIF-1α axis.

This study was designed to explore the effects of exosomal miR-421 secreted by cancer-associated fibroblasts (CAFs) on pancreatic cancer (PC) progression and the mechanisms involved. CAFs and exosomes (exos) were isolated and identified. PC cells were treated with CAF-derived exos (CAF-exos). Western blotting and quantitative polymerase chain reaction (qPCR) were used to measure miR-421, sirtuin-3 (SIRT3), and hypoxia duciblefactors-1 alpha (HIF-1α) levels. Cell counting kit-8 (CCK-8), wound-healing, and transwell migration assays were used to measure proliferation, migration, and invasion abilities of the cells. Dual-luciferase assay and RNA immunoprecipitation (RIP) experiment analyzed the relationship between miR-421 and SIRT3. Chromatin immunoprecipitation (f)-verified H3K9Ac enrichment in the HIF-1α promoter region. In vivo tumorigenesis experiments were performed to further explore the effects of exosomal miR-421 from CAFs on PC. CAFs and exos were successfully isolated. CAF-exo-treated PC cells highly expressed miR-421 and had increased cell proliferation, migration, and invasion abilities. Knocking down miR-421 increased the expression of SIRT3. SIRT3 is a target of miR-421, and inhibiting the expression of SIRT3 reversed the negative effects of miR-421 knockdown on PC cell. Knocking down miR-421 in CAF-exo inhibited the expression of HIF-1α in PC cells. Moreover, SIRT3-mediated HIF-1α expression by regulating H3K9Ac. HIF-1α overexpression reversed the inhibiting effects of SIRT3 overexpression on PC progression and counteracted the inhibiting effects of miR-421 knockdown on glycolysis. Moreover, in vivo tumorigenesis experiments showed that knocking down miR-421 attenuated CAF-exo induced tumor growth. Exosomal miR-421 from CAFs promoted PC progression by regulating the SIRT3/H3K9Ac/HIF-1α axis. This study provided insights into the molecular mechanism of PC.

LINC00960 regulates cell proliferation and glycolysis in pancreatic cancer through the miR-326-3p/TUFT1/AKT-mTOR axis.

Pancreatic cancer (PC) is a common malignant cancer characterized by high mortality and poor prognosis. LINC00690 was involved in the occurrence and progression of PC, but the underlying mechanisms require further investigation. The goal of this study was to figure out how LINC00960 mediates glycolysis in PC. LINC00960, miR-326-3p, and Tuftelin 1 (TUFT1) expression levels were detected in PC cell lines. LINC00960 and TUFT1 expression levels were increased in PC cells when compared with normal pancreatic cells, whereas miR-326-3p expression levels were decreased. The expression levels of LINC00690 affected glycolysis in PC, and inhibition of LINC00960 inhibited tumor growth in vivo. LINC00690 targeted and suppressed the expression of miR-326-3p. MiR-326-3p bound to TUFT1, and miR-326-3p inhibited AKT-mTOR pathway activation via TUFT1. In conclusion, the depletion of LINC00960 repressed cell proliferation and glycolysis in PC by mediating the miR-326-3p/TUFT1/AKT-mTOR axis. Thus, we present a novel mechanism underlying the progression of PC that suggests LINC00960 is a potential therapeutic target for this cancer.

Obesity and pancreatic cancer: An update of epidemiological evidence and molecular mechanisms.

Despite advances in therapy and achievements in translational research, pancreatic cancer (PC) remains an invariably fatal malignancy. Risk factors that affect the incidence of PC include diabetes, smoking, obesity, chronic pancreatitis, and diet. The growing worldwide obesity epidemic is associated with an increased risk of the most common cancers, including PC. Chronic inflammation, hormonal effects, circulating adipokines, and adipocyte-mediated inflammatory and immunosuppressive microenvironment are involved in the association of obesity with PC. Herein, we systematically review the epidemiology of PC and the biological mechanisms that may account for this association. Included in this review is a discussion of adipokine-mediated inflammation, lipid metabolism, and the interactions of adipocytes with cancer cells. We consider the influence of bariatric surgery on the risk of PC risk as well as potential molecular targets of therapy. Our review leads us to conclude that targeting adipose tissue to achieve weight loss may represent a new therapeutic strategy for preventing and treating PC.

Warshaw Technique in Laparoscopic Spleen-Preserving Distal Pancreatectomy: Surgical Strategy and Late Outcomes of Splenic Preservation.

Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) can be accomplished with either the preservation or the resection of splenic vessels; the latter is also known as Warshaw technique. Our study is designed to investigate the operation selection strategy when proceeding LSPDP and to evaluate the long-term outcomes of patients undergoing Warshaw surgery. The medical records and follow-up data of patients who underwent LSPDP in Qilu Hospital, Shandong University, were reviewed retrospectively. A total of thirty-five patients were involved in this study, including 17 cases of patients who were treated with Warshaw procedure (WT) while the other 18 cases had splenic vessels preserved (SVP). Compared with the SVP group, the operative time and intraoperative blood loss in WT group were improved significantly. The incidence of early postoperative splenic infarction was higher in WT group. However, there was no report of splenic abscess or second operation. Follow-up data confirmed that there was no significant difference in spleen phagocytosis and immune function compared with normal healthy population. Our study confirms that LSPDP-Warshaw procedure is a safe and efficient treatment for the benign or low grade malignant tumors in distal pancreas in selected patients. The long-term spleen function is normal after Warshaw procedure. Preoperative assessment and intraoperative exploration are recommended for the selection of operation approaches.

Cystic pancreatic neuroendocrine tumors: A distinctive subgroup with indolent biological behavior? A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The clinicopathological features and biological behaviors of cystic pancreatic neuroendocrine tumors (pNETs) are unclear and controversial. Here we performed a systematic review and meta-analysis to investigate the unique characteristics of cystic pNETs, to determine whether they represent a distinct clinical entity. METHODS: We selected comparative studies published since January 2000 that explore the differences between clinicopathological features of cystic and solid pNETs. Demographic information, pathological characteristics, and survival information were analyzed. RESULT: The 12 selected studies comprised 355 and 1530 patients diagnosed with cystic and solid pNETs, respectively. Compared with solid pNETs, cystic pNETs were less likely to be functional (odds ratio, OR = 0.31, 95% confidence interval (CI) 0.19-0.50, p < 0.00001), more likely to affect males (OR = 1.56, 95% CI 1.22-2.00, p = 0.0005), and significantly associated with multiple endocrine neoplasia type 1 (OR = 2.71). Cystic pNETs were more likely to present with G1 and G2 rather than G3 (OR = 1.66). Cystic pNETs were associated with less frequent distant organs and lymph node metastasis, microvascular invasion, perineural invasion, and a low Ki-67 index and mitotic count. There were no significant differences between 5- and 10-year overall survival. However, the 5-year disease-free survival (DFS) and 10-year DFS rate of patients with cystic pNETs was significantly higher compared with those with solid pNETs (94.6% vs 83.5%, OR = 3.00; 92.7% vs 63.6%, OR = 5.92, respectively). CONCLUSIONS: Cystic pNETs represent a distinct subgroup of pNETs that present with an indolent biological behavior, and patients experience better DFS. Observation and surveillance should be considered in some selected cases.

A nanoporous carbon derived from bimetallic organic-framework for magnetic solid-phase extraction of bisphenol analogs.

Taking Zn-Fe bimetallic organic-framework as both template and precursor, and furfuryl alcohol (FA) as secondary carbon source, a high-surface-area magnetic nanoporous carbon (MNPC) material was successful prepared. The MNPC exhibits excellent adsorption performance for bisphenol analogs (BPs). The maximum adsorption capacity achieved 439.0 mg g-1 for bisphenol AF, 423.7 mg g-1 for bisphenol S, 330.4 mg g-1 for tetrabromobisphenol A and 252.5 mg g-1 for bisphenol A. A sensitive magnetic solid-phase extraction with MNPC as adsorbent coupled with HPLC-UV analytical method was developed for the detection of trace BPs. The limits of detection for BPs were as low as 0.03-0.07 ng mg-1 with the RSDs of less than 4.6%. This method was applied to detection of four BPs in environmental water samples and the satisfactory results were obtained.

Selective adsorption and separation of illegal cationic dyes from foodstuffs with anionic polyelectrolyte functionalised metal-organic frameworks.

A novel adsorbent, poly(sodium 4-styrenesulfonate) modified MIL-101(Cr)-NH2, was successfully prepared. Owing to its high surface area and degree of negative surface charge, it enables effective adsorption and separation of illegal cationic dyes, such as rhodamine B, pararosaniline, and auramine O, from foodstuffs prior to high performance liquid chromatography analysis. Under optimised conditions, good linearity was obtained over 1.0-80.0 or 1.0-120 ng mL-1 with a correlation coefficient (R2) > 0.999. Limits of detection and limits of quantification of the three dyes were 0.28-0.65 and 0.94-2.13 µg kg-1, respectively. The recoveries of the three dyes in shrimp powder, chili powder, tofu sheets, and tomato sauce were in the range of 86.8-119.3%, suggesting that the developed method is a promising tool for accurate quantification of the three dyes at trace levels in foodstuffs.

Effects of growth hormone and functional appliance on mandibular growth in an adolescent rat model.

OBJECTIVES: To investigate the individual and synergistic effects of growth hormone (GH) and functional appliance (FA) on mandibular growth in an adolescent rat model. MATERIALS AND METHODS: Forty adolescent (6-week-old) female Wistar rats were randomly divided into four groups (10 rats in each group). The control group received a sham treatment (intra-abdominal injection of phosphate-buffered saline), the GH group received an intra-abdominal injection of recombinant human growth hormone, the FA group was treated with a mandibular advancement device, and the GH+FA group received both the GH and FA treatments. The amount of mandibular growth in each group was measured quantitatively using cone-bean computed tomography. The growth of condylar cartilage and expression of matrix metalloproteinases-1 and -13 (MMP-1 and MMP-13) and type II and X collagen (Col II and Col X) were assessed using histological staining and immunostaining techniques. RESULTS: After 4 weeks, there was significant mandibular growth in the FA group compared with the control group ( P < .05). The GH+FA group had significantly greater mandibular length, thickness of condylar cartilage, and expression of MMP-1, MMP-13, Col II, and Col X in the cartilage than the other groups ( P < .05). The GH+FA group and GH group had significantly greater weight than the FA and control groups ( P < .05). CONCLUSIONS: The FA as well as GH+FA stimulated mandibular growth in adolescent rats.

Immunotherapy for pancreatic cancer: A long and hopeful journey.

Multiple therapeutic strategies have been developed to treat pancreatic cancer. However, the outcomes of these approaches are disappointing. Due to deeper understandings of the pivotal roles of the immune system in pancreatic cancer tumorigenesis and progression, novel therapeutic strategies based on immune cells and the tumor microenvironment are being investigated. Some of these approaches, such as checkpoint inhibitors, chimeric antigen receptor T-cell therapy, and BiTE antibodies, have achieved exciting outcomes in preclinical and clinical trials. The current review describes the roles of immune cells and the immunosuppressive microenvironment in the development of pancreatic cancer, as well as the preclinical and clinical outcomes and benefits of recent immunotherapeutic approaches, which may help us further disclose the mechanisms of pancreatic cancer progression and the dialectical views of feasibility and effectiveness of immunotherapy in treatment of pancreatic cancer.

miR-146b-5p regulates cell growth, invasion, and metabolism by targeting PDHB in colorectal cancer.

MiRNA have been found to play a role in a plethora of cellular processes of cancer cells such as cell apoptosis, cell proliferation, invasion, migration metabolism and stem cell differentiation. Dysregulation of miR-146b-5p has been documented in a variety of human malignancies. However, the biological functions and molecular mechanisms of miR-146b-5p in ovarian cancer remain unknown. In this study, our results show that miR-146b-5p was unregulated in colorectal cancer (CRC) tissues compared with the adjacent non-cancerous tissues. Ectopic overexpression of miR-146b-5p in CRC promoted cell growth, invasion and glycolysis, while knockdown of miR-146b-5p inhibited the growth, invasion and glycolysis of CRC cells. The oncogenic effect of miR-146b-5p is also confirmed in vivo. Mechanically, miR-146b-5p targets the 3'-UTR of pyruvate dehydrogenase B (PDHB) and exerts oncogenic effect. Overexpression of PDHB abolished the oncogenic effects of miR-146b-5p on the growth, invasion and glycolysis of CRC cells. Taken together, our results show that miR-146b-5p is an oncogenic miRNA in CRC which exerts its effect by directly targeting PDHB.

Neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of prospective studies.

There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer (PC). However, study results have varied significantly. In this study, a systematic review and meta-analysis of prospective studies were performed in order to evaluate safety and effectiveness of neoadjuvant therapy in PC. Thirty-nine studies were selected (n = 1458 patients), with 14 studies focusing on patients with resectable disease (group 1), and 19 studies focusing on patients with borderline resectable and locally advanced disease (group 2). Neoadjuvant chemotherapy was administered in 97.4% of the studies, in which 76.9% was given radiotherapy and 74.4% administered with chemoradiation. The complete and partial response rate was 3.8% and 20.9%. The incidence of grade 3/4 toxicity was 11.3%. The overall resection rate after neoadjuvant therapy was 57.7% (group 1: 73.0%, group 2: 40.2%). The R0 resection rate was 84.2% (group 1: 88.2%, group 2: 79.4%). The overall survival for all patients was 16.79 months (resected 24.24, unresected 9.81; group 1: 17.76, group 2: 16.20). Our results demonstrate that neoadjuvant therapy has not been proven to be beneficial and should be considered with caution in patients with resectable PC. Patients with borderline resectable or locally advanced disease may benefit from neoadjuvant therapy, but further research is needed.

Crosstalk between stromal cells and cancer cells in pancreatic cancer: New insights into stromal biology.

Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide. Increasing evidence has confirmed the pivotal role of stromal components in the regulation of carcinogenesis, invasion, metastasis, and therapeutic resistance in PC. Interaction between neoplastic cells and stromal cells builds a specific microenvironment, which further modulates the malignant properties of cancer cells. Instead of being a "passive bystander", stroma may play a role as a "partner in crime" in PC. However, the role of stromal components in PC is complex and requires further investigation. In this article, we review recent advances regarding the regulatory roles and mechanisms of stroma biology, especially the cellular components such as pancreatic stellate cells, macrophages, neutrophils, adipocytes, epithelial cells, pericytes, mast cells, and lymphocytes, in PC. Crosstalk between stromal cells and cancer cells is thoroughly investigated. We also review the prognostic value and molecular therapeutic targets of stroma in PC. This review may help us further understand the molecular mechanisms of stromal biology and its role in PC development and therapeutic resistance. Moreover, targeting stroma components may provide new therapeutic strategies for this stubborn disease.

Early detection of pancreatic cancer: Where are we now and where are we going?

Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various "omics" studies including genomics, epigenomics, non-coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine and saliva). Although many biomarkers for early detection of PC have been discovered through various methods, larger scale and rigorous validation is required before their application in the clinic. In addition, more effective and specific biomarkers of PC are urgently needed.

Safety and Efficacy of Doxofylline for Treating the Patients With Ticagrelor Caused Dyspnea / 中国循环杂志

Objective:To study the safety and efficacy of doxofylline for treating the patients with ticagrelor caused dyspnea.Methods:A total 172 coronary artery disease (CAD) patients with ticagrelor caused dyspnea in our hospital from 2015-02 to 2016-07 were studied.The patients were divided into 2 groups:Intervention group,patients received doxofylline at 200 mg twice per day for 5 days and Control group,patients received placebo.n=86 in each group.Dyspnea remission rate of was recorded at 1 day after treatment;platelet aggregation rate before and after treatment,cardiac death,myocardial infarction (MI),stroke,bleeding and other adverse cardiovascular and cerebral events were compared at 6 month after treatment.Results:Compared with Control group,Intervention group had improved dyspnea remission rate at 1 day after treatment (93％ vs 63％),P＜0.05;platelet aggregation rate [before doxofylline application:(35.53±5.1)％ vs (35.16±4.6)％,after doxofylline application:(26.48±4.3)％ vs(25.98±4.7)％]adverse cardiovascular and cerebral events were similar between 2 groups before and after doxofylline application,P＞0.05.Conclusion:Doxofylline was effective for treating the patients with ticagrelor caused dyspnea,it does not affect platelet aggregation effect of ticagrelor.