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Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

Chinese Journal of Cancer Research 2024年第2期36卷 124-137页

作者： Jialin Zhang Gengshen Yin Chunmiao Ye Man Feng Changhua Ji Wenzhong Zhou Fei Wang Lixiang Yu Shuya Huang Zhigang Yu Department of Breast Surgery the Second Hospital of Shandong UniversityJinan 250033China Institute of Translational Medicine of Breast Disease Prevention and Treatment Shandong UniversityJinan 250033China Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease Jinan 250033China Department of Pathology the Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China Department of Pathology the Second Hospital of Shandong UniversityJinan 250033China

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is ***: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to ***: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft ***: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance

关键词： Breast cancer HER2 pyrotinib trastuzumab primary resistance pertuzumab

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Mechanical regulation of lipid and sugar absorption by Piezo1 in enterocytes

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3576-3590页

作者： Tian Tao Qing Shu Yawen Zhao Wenying Guo Jinting Wang Yuhao Shi Shiqi Jia Hening Zhai Hui Chen Cunchuan Wang Geyang Xu Department of Physiology School of MedicineJinan UniversityGuangzhou 510632China Department of Metabolic and Bariatric Surgery the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Endoscopy Center the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Biotherapy Center Cell-gene Therapy Translational Medicine Research Centerthe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(jinan University) Ministry of EducationGuangzhou 510632China

Obesity is primarily caused by excessive intake as well as absorption of sugar and *** surge in distention pressure and intestinal motility accelerates the absorption of *** response of intestinal epithelial cells to mechanical stimulation is not fully ***1,a mechanosensitive ion channel,is widely expressed throughout the digestive ***,its function in intestinal nutrient absorption is not yet *** our study,excessive lipid deposition was observed in the duodenum of obese patients,while duodenal Piezo1-CaMKK2-AMPKa was decreased when compared to normal-weight *** high-fat diet condition,the Piezo1iKO mice exhibited abnormally elevated sugar and lipid absorption as well as severe lipid deposition in the duodenum and *** phenotypes were mainly caused by the inhibition of duodenal CaMKK2-AMPKa and the upregulation of SGLT1 and *** contrast,Yoda1,a Piezo1 agonist,was found to reduce intestinal lipid absorption in diet induced obese *** of Piezo1,stretch and Yoda1 inhibited lipid accumulation and the expression of DGAT2 and SGLT1,whereas knockdown of Piezo1 stimulated lipid accumulation and DGAT2 in Caco-2 *** study reveals a previously unexplored mechanical regulation of nutrient absorption in intestinal epithelial cells,which may shed new light on the therapy of obesity.

关键词： Piezo1 DGAT2 SGLT1 Lipid metabolism Obesity Mechanical sensing Intestinal lipid absorption Intestinal glucose absorption

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Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2613-2630页

作者： Xuemin He Siying Wen Xixiang Tang Zheyao Wen Rui Zhang Shasha Li Rong Gao Jin Wang Yanhua Zhu Dong Fang Ting Li Ruiping Peng Zhaotian Zhang Shiyi Wen Li Zhou Heying Ai Yan Lu Shaochong Zhang Guojun Shi Yanming Chen Department of Endocrinology and Metabolic Diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Guangdong Provincial Key Laboratory of Diabetology&Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity Research the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China VIP Medical Service Center the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Clinical Immunology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Ophthalmology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Department of Fundus Shenzhen Eye Hospital of Jinan UniversityShenzhen 518048China

Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)protect against diabetic cardiovascular diseases and ***,their activity in diabetic retinopathy(DR)remains *** retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications,suggesting their advantage in DR *** single-cell RNA-sequencing analysis and immunostaining,we observed a high expression of GLP-1R in retinal endothelial cells,which was down-regulated under diabetic *** of GLP-1 RAs significantly restored the receptor expression,resulting in an improvement in retinal degeneration,vascular tortuosity,avascular vessels,and vascular integrity in diabetic *** and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 ***,the treatment attenuated STING signaling activation in retinal endothelial cells,which is typically activated by leaked mitochondrial *** of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular *** investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING *** study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

关键词： GLP-1 RAs STING signaling Retinal endothelial cells Mitochondrial leakage Retinal vascular dysfunction Diabetic retinopathy CREB Inflammation

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Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

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Chinese Journal of Cancer Research 2024年第2期36卷 114-123页

作者： Yupeng Ren Yuxuan Li Mingbo Cao Yongchang Tang Feng Yuan Gaoyuan Yang Zhiwei He Zheng Shi Xiaorui Su Zhicheng Yao Meihai Deng Department of Hepatobiliary Surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Department of General Surgery Qilu HospitalShandong UniversityJinan 250012China Department of Hepatobiliary Surgery the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Hepatobiliary and Pancreatic Surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of ***: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) *** OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher ***: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

关键词： Hepatocellular carcinoma lenvatinib low-dose cyclophosphamide pembrolizumab transarterial chemoembolization

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Analysis of the Application of Sports Medicine Ultrasound in the Rehabilitation of Anterior Talofibular Ligament Injury

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Proceedings of Anticancer Research 2024年第3期8卷 144-149页

作者： Ling Dong Yanyan Chu jinan third People’s hospital Jinan 250100Shandong ProvinceChina

Objective: To explore the application effect of sports medicine ultrasound in the rehabilitation treatment of anterior talofibular ligament injury. Methods: 36 patients who visited our hospital from January 2020 to September 2023 were selected as research subjects and randomly divided into the study group (18 cases) and the control group (18 cases). The control group adopted routine examination and rehabilitation training, and the study group adopted sports medicine ultrasound and rehabilitation training. The ankle function scores and daily living ability of the two groups were compared before treatment and 9 weeks after treatment. Results: There was no statistically significant difference between the study group and the control group in terms of ankle function scores and ability to perform activities of daily living before treatment (P > 0.05), but the difference was statistically significant after treatment (P < 0.05). Conclusion: Ultrasound can be used as a supplement to magnetic resonance imaging (MRI) of the ankle joint for diagnosing anterior talofibular ligament injury;ultrasound can show the location, distance, and degree of tear of the anterior talofibular ligament rupture and accurately predict muscle atrophy around the ankle joint;ultrasound combined with computed tomography (CT) can better determine the type of intra-articular fracture of the talar subtalar joint, and guide the choice of surgical timing. In addition, ultrasound can be used to determine the severity of peroneal muscle atrophy, assess the progress of early postoperative functional exercise, and guide personalized rehabilitation programs.

关键词： Sports medicine ultrasound Anterior talofibular ligament injury Rehabilitation

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Is reactive oxygen species the only way for cancer inhibition over single atom nanomedicine?Autophagy regulation also works

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Chinese Chemical Letters 2024年第6期35卷 474-479页

作者： Yuanyi Zhou Ke Ma Jinfeng Liu Zirun Zheng Bo Hu Yu Meng Zhizhong Li Mingshan Zhu Postdoctoral Innovation Practice Base The First and Fifth Affiliated Hospital of Jinan UniversityGuangzhou 510632China Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction The Fifth Affiliated Hospital of Jinan University(Heyuan Shenhe People’s Hospital)Heyuan 517465China School of Environment Jinan UniversityGuangzhou 511443China Department of Nephrology The First Affiliated Hospital of Jinan UniversityGuangzhou 510632China

Exploring the therapeutic effect of single atom catalysts beyond reactive oxygen species(ROS)modulation would boost the prosperity of nanomedicine in cancer *** as a vital therapy target offers new options for the control of renal cell carcinoma(RCC)***,Fe single atom-decorated graphene oxide(Fe_(1)-GO)nanosheet is developed to be a feasible autophagy inducer in RCC *** the well-dispersed O-Fe_(1)-O active sites,Fe_(1)-GO kills ACHN cells effectively but maintains acceptable cytotoxicity to the normal podocyte and HK2 ***-depth analyses ascribe the inhibition of ACHN cells to the upregulated autophagy instead of the commonly known catalytic ROS *** in vivo therapeutic effect of Fe_(1)-GO nanomedicine is also validated by the RCC-bearing BALB/c mice model,realizing an 89% reduction of tumor weight and good *** work provides new insights into the design of autophagy regulators as well as potential therapeutic strategies for RCC treatment.

关键词： Fe single atom Autophagy Renal cell carcinoma Graphene oxide Cancer therapy

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Identification of risk factors and construction of a nomogram predictive model for post-stroke infection in patients with acute ischemic stroke

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World Journal of Clinical Cases 2024年第20期12卷 4048-4056页

作者： Xiao-Chen Liu Xiao-Jie Chang Si-Ren Zhao Shan-Shan Zhu Yan-Yan Tian Jing Zhang Xin-Yue Li Department of Neurosurgery Shandong Provincial Third HospitalJinan 250031Shandong ProvinceChina Department of Neurology Shandong Provincial Third HospitalJinan 250031Shandong ProvinceChina

BACKGROUND Post-stroke infection is the most common complication of stroke and poses a huge threat to *** addition to prolonging the hospitalization time and increasing the medical burden,post-stroke infection also significantly increases the risk of disease and *** the risk factors for post-stroke infection in patients with acute ischemic stroke(AIS)is of great *** can guide clinical practice to perform corresponding prevention and control work early,minimizing the risk of stroke-related infections and ensuring favorable disease *** To explore the risk factors for post-stroke infection in patients with AIS and to construct a nomogram predictive *** The clinical data of 206 patients with AIS admitted to our hospital between April 2020 and April 2023 were retrospectively *** data and post-stroke infection status of all study subjects were assessed,and the risk factors for poststroke infection in patients with AIS were *** Totally,48 patients with AIS developed stroke,with an infection rate of 23.3%.Age,diabetes,disturbance of consciousness,high National Institutes of Health Stroke Scale(NIHSS)score at admission,invasive operation,and chronic obstructive pulmonary disease(COPD)were risk factors for post-stroke infection in patients with AIS(P<0.05).A nomogram prediction model was constructed with a C-index of 0.891,reflecting the good potential clinical efficacy of the nomogram prediction *** calibration curve also showed good consistency between the actual observations and nomogram *** area under the receiver operating characteristic curve was 0.891(95%confidence interval:0.839–0.942),showing predictive value for post-stroke *** the optimal cutoff value was selected,the sensitivity and specificity were 87.5%and 79.7%,*** Age,diabetes,disturbance of consciousness,NIHSS score at admission,invasive surgery,and COPD are risk factors for post-st

关键词： Acute ischemic stroke Infection Risk factors Nomogram prediction model Chronic obstructive pulmonary disease

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Palmitoleic acid on top of HFD ameliorates insulin resistance independent of diacylglycerols and alters gut microbiota in C57BL/6J mice

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Food Science and Human Wellness 2024年第2期13卷 856-868页

作者： Qijian Liang Yan Zheng Fanli Meng Xiaofan Jiang Qingcai Zhen Zhongting Lu Shixiu Zhang Lei Du Hao Wu Xin Guo Department of Nutrition and Food Hygiene School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China Research Center of Translational Medicine Jinan Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013China Department of Hepatology Qilu Hospital of Shandong UniversityJinan 250012China Institute of Hepatology Shandong UniversityJinan 250012China

With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic *** acid is a monounsaturated fatty acid that is available from dietary sources,mainly derived from marine products.P almitoleic acid plays a positive role in maintaining glucose homeostasis and reducing ***,it is still unknow the mechanism of palmitoleic acid in ameliorating insulin ***,we investigated the effects of palmitoleic acid on chow diet(CD)-fed and high-fat diet(HFD)-fed mice,which were fed CD or HFD for 12 weeks before *** administrated mice with BSA(control),oleic acid,or palmitoleic acid for 6 weeks on top of CD or HFD *** found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing *** study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes *** colon,palmitoleic acid increased intestinal tight junction integrity and reduced ***,palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose ***(DAG)in tissue(for example,liver)is found to positively correlated with *** enhanced the levels of DAGs in liver but not in adipose tissue in this *** acid did not reverse the high DAG levels induced by HFD in ***,in HFD-fed mice,palmitoleic acid reduced insulin resistance by an independent-manner of *** might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition,improving of intestinal barrier function,and downregulating the inflammation in colon,liver,and adipose tissue.

关键词： Palmitoleic acid High fat diet Insulin resistance Gut microbiota

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Penumbra-targeted CircOGDH siRNA-loaded nanoparticles alleviate neuronal apoptosis in focal brain ischaemia

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Stroke & Vascular Neurology 2024年第2期9卷 134-144,I0396-I0413页

作者： Yanfang Liu Tianyuan Zhang Xing Zou Zhongwen Yuan Yufeng Li Jiankun Zang Niu He Lizhen He Anding Xu Dan Lu Department of Neurology and Stroke Center Jinan University First Affiliated HospitalGuangzhouGuangdongChina Department of Clinical Neuroscience Institute The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdongChina Key Lab of Guangzhou Basic and Translational Research of Pan-vascular Diseases The First Affiliated Hospital of Jinan UniversityGuangzhouChina

Background Nanoparticles(NPs)are a class of substances that can be loaded with therapeutic agents delivered to specific *** our earlier research,we identified a neuron-derived circular RNA(circRNA),circular oxoglutarate dehydrogenase(CircOGDH),as a promising therapeutic target for acute ischaemic *** study dedicated to explore a prospective preliminary strategy of CircOGDH-based NP delivered to the ischaemic penumbra region in middle cerebral artery occlusion/reperfusion(MCAO/R)*** Immunofluorescence in primary cortex neurons and in vivo fluorescence imaging revealed endocytosis of Poly(lactide-co-glycolide)(PLGA)poly amidoamine(PAMAM)@CircOGDH small interfering RNA(siRNA)*** blotting analysis and CCK8 assay were performed to evaluate the apoptotic level in ischaemic neurons treated with PLGA–PAMAM@CircOGDH siRNA *** reverse transcription PCR experiments,mice behaviour test,T2 MRI analysis,Nissl and TdT-mediated dUTP nick end labeling(TUNEL)co-staining were performed to evaluate the apoptosis level of ischaemic penumbra neurons in MCAO/R *** evaluation of NPs in MCAO/R mice was detected by blood routine examination,liver and kidney function examination and HE *** PLGA–PAMAM@CircOGDH siRNA NPs were successfully *** of PLGA–PAMAM@CircOGDH siRNA NPs in ischaemic neurons alleviated neuronal apoptotic level in vitro and in ***,mice behaviour test showed that the neurological defects of MCAO/R mice were significantly alleviated after the tail injection of PLGA–PAMAM@CircOGDH siRNA NPs,and no toxic effects were *** In conclusion,our results suggest that PLGA–PAMAM@CircOGDH siRNA NPs can be delivered to the ischaemic penumbra region and alleviate neuron apoptosis in MCAO/R mice and in ischaemic neurons;therefore,our study provides a desirable approach for using circRNA-based NPs for the treatment of ischaemic stroke.

关键词： OGD routine loaded

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Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway

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Asian Journal of Andrology 2024年第1期26卷 57-66页

作者： Chang-Bo Zhao Wei-Bo Chen Wen-Zhen Wang Fang-Xin Gong Cui-Qin Fan Ye Li Tian Lan Wen-Jing Wang Ming-Zhen Yuan Department of Urology Shandong Provincial HospitalShandong UniversityJinan 250012China Department of Andrology Liaocheng People's HospitalShandong UniversityLiaocheng 252000China Department of Urology The Second Hospital of Shandong UniversityJinan 250012China Department of Physiology School of Basic Medical SciencesShandong UniversityJinan 250012China

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction(DMED)a challenging *** factors contributing to DMED include oxidative stress,nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)pathway activation,and apoptosis,while nitro-oleic acid(NO,-OA)has been shown to be beneficial in treating these aspects of this ***,herein,investigated the effects and possible mechanisms of NO,-OA on erectile function as assessed in a streptozotocin-induced rat model of *** results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control ***,in response to 4 weeks of NO,-OA treatment,there was an improvement in erectile *** expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED *** expression of proapoptotic factors was increased,while that of antiapoptotic factors was decreased in the DMED ***,the cell morphology in the cavernous tissue of the DMED group also changed ***,-OA treatment significantly reversed all these changes observed in the DMED *** conclusion,NO,-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress,activation of the NO/cGMP pathway,and a reduction in apoptosis.

关键词： apoptosis diabetic mellitus erectile dysfunction nitro-oleic acid NO/cGMP pathway oxidative stress

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