22 results on '"YaQian Xu"'
Search Results
2. The Long-term Effect of Dobutamine on Intrinsic Myocardial Function and Myocardial Injury in Septic Rats with Myocardial Dysfunction
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Xiangxu Tang, Duomeng Yang, Yaqian Xu, Huadong Wang, Qingyang Huang, Yun Xing, Hongmei Li, Daxiang Lu, Yiyang Wang, Xiuxiu Lv, and Xiaomeng Dai
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Male ,Inotrope ,medicine.medical_specialty ,Cardiac output ,Cardiotonic Agents ,Time Factors ,medicine.drug_class ,Cardiomyopathy ,Hemodynamics ,Critical Care and Intensive Care Medicine ,Rats, Sprague-Dawley ,Sepsis ,Dobutamine ,Internal medicine ,Troponin I ,medicine ,Natriuretic peptide ,Animals ,business.industry ,medicine.disease ,Rats ,Disease Models, Animal ,Heart Injuries ,Emergency Medicine ,Cardiology ,Cytokines ,Cardiomyopathies ,business ,medicine.drug - Abstract
Dobutamine (DOB) is recommended as an inotrope for septic patients with low cardiac output, but its long-term impact on sepsis-induced cardiomyopathy remains unclear. This study investigated the long-term effect of DOB on septic myocardial dysfunction and injury. Rats were exposed to cecal ligation and puncture (CLP), the intrinsic myocardial function, other organ functions, hemodynamics, inflammatory response, serum myocardial injury biomarkers, myocardial apoptosis, and vascular permeability were determined. At 6 h after CLP, the left ventricular ±dP/dt were significantly depressed, cardiac tumor necrosis factor-α and vascular cell adhesion molecule-1 expression were increased, but not serum cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), creatinine, and urea nitrogen concentrations in CLP group compared with controls. At 9 h after CLP, hepatic dysfunction was present in CLP rats compared with controls. At 6 h after CLP, DOB treatment did not affect hemodynamics, the left ventricular ±dP/dt, cytokine levels in serum and myocardium, as well as cardiomyocyte apoptosis and cardiac vascular hyperpermeability at 20 h after CLP. However, DOB (10.0 μg/kg) increased serum IL-10 level and improved survival in septic rats. These results indicate that the intrinsic myocardial depression occurs earlier than hepatic and renal dysfunction in sepsis and serum cTnI, NT-proBNP, and H-FABP are not suitable as early biomarkers for sepsis-induced myocardial dysfunction. Although DOB treatment (10.0 μg/kg) in the presence of myocardial dysfunction improves survival in septic rats, it neither improves myocardial function and hemodynamics nor attenuates myocardial injury at the later stage of sepsis.
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- 2021
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3. Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia
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Rongmei Tang, Bai-Yan Liu, Piao Zheng, Bo-Wei Chen, Jian Yi, and Yaqian Xu
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Male ,Ischemia ,RM1-950 ,Pharmacology ,Neuroprotection ,Brain Ischemia ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,microRNA ,CeRNA ,Animals ,Medicine ,RNA, Messenger ,Regulation of gene expression ,Dose-Response Relationship, Drug ,Glial fibrillary acidic protein ,biology ,business.industry ,Infarction, Middle Cerebral Artery ,RNA, Circular ,General Medicine ,Cerebral ischemia ,medicine.disease ,Rats ,Butylphthalide ,CircRNA ,MicroRNAs ,Neuroprotective Agents ,Gene Expression Regulation ,chemistry ,Hippo signaling ,Disease Progression ,biology.protein ,Neurovascular unit ,Immunohistochemistry ,Therapeutics. Pharmacology ,business ,MiRNA ,Buyang Huanwu Decoction ,Drugs, Chinese Herbal ,Signal Transduction - Abstract
Background and aim: Buyang Huanwu Decoction (BHD) is a traditional Chinese herbal medicine that is effective for treating cerebral ischemia (CI). However, the molecular mechanisms of BHD in CI have not been fully elucidated. In this study, we integrated the circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) network of middle cerebral artery occlusion (MACO) rats treated with BHD. Methods: SD rats were randomly divided into a control group, model group, model+BHD group (2.5, 5, 10 g/kg) and model+butylphthalide (NBP) group (54 mg/kg). The neurological functions of the rats were evaluated by a modified neurological severity scoring (mNSS) system. Pathological lesions were assessed by Nissl staining, and the effects of BHD on neurovascular unit (NVU) associated protein microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP) and von Willebrand factor (VWF) were assessed by immunohistochemistry. CeRNA and miRNA microarrays were used to establish the circRNA, miRNA, and mRNA profiles. Finally, a circRNA-miRNA-mRNA ternary transcription network was constructed. Results: BHD improved the neurobehavioral test scores (P
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- 2022
4. Dexmedetomidine Promotes Lipopolysaccharide-Induced Differentiation of Cardiac Fibroblasts and Collagen I/III Synthesis through α2A Adrenoreceptor-Mediated Activation of the PKC-p38-Smad2/3 Signaling Pathway in Mice
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Jiashuo Teng, Xiaomeng Dai, Jia Liao, Yiyang Wang, Hongmei Li, Huadong Wang, Xiuxiu Lv, Xiangxu Tang, Yingwei Wang, Xingyu Su, Kaiying Li, Yun Xing, Yaqian Xu, and Yihua Chen
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Lipopolysaccharides ,Male ,Cardiac fibrosis ,Stimulation ,Smad2 Protein ,p38 Mitogen-Activated Protein Kinases ,Mice ,polycyclic compounds ,Adrenergic alpha-2 Receptor Agonists ,Biology (General) ,Myofibroblasts ,Spectroscopy ,Protein Kinase C ,Chemistry ,lipopolysaccharide ,virus diseases ,dexmedetomidine ,Cell Differentiation ,General Medicine ,differentiation ,cardiac fibroblast ,α2 adrenergic receptor ,Computer Science Applications ,Knockout mouse ,Tumor necrosis factor alpha ,Signal transduction ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction ,Agonist ,musculoskeletal diseases ,medicine.medical_specialty ,QH301-705.5 ,medicine.drug_class ,p38 mitogen-activated protein kinases ,Catalysis ,Article ,Collagen Type I ,Inorganic Chemistry ,Receptors, Adrenergic, alpha-2 ,Internal medicine ,medicine ,Animals ,Smad3 Protein ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Protein kinase C ,Organic Chemistry ,medicine.disease ,nervous system diseases ,Mice, Inbred C57BL ,Endocrinology ,Collagen Type III ,Gene Expression Regulation - Abstract
Dexmedetomidine (DEX), a selective α2 adrenergic receptor (AR) agonist, is commonly used as a sedative drug during critical illness. In the present study, we explored a novel accelerative effect of DEX on cardiac fibroblast (CF) differentiation mediated by LPS and clarified its potential mechanism. LPS apparently increased the expression of α-SMA and collagen I/III and the phosphorylation of p38 and Smad-3 in the CFs of mice. These effects were significantly enhanced by DEX through increasing α2A-AR expression in CFs after LPS stimulation. The CFs from α2A-AR knockout mice were markedly less sensitive to DEX treatment than those of wild-type mice. Inhibition of protein kinase C (PKC) abolished the enhanced effects of DEX on LPS-induced differentiation of CFs. We also found that the α-SMA level in the second-passage CFs was much higher than that in the nonpassage and first-passage CFs. However, after LPS stimulation, the TNF-α released from the nonpassage CFs was much higher than that in the first- and second-passage CFs. DEX had no effect on LPS-induced release of TNF-α and IL-6 from CFs. Further investigation indicated that DEX promoted cardiac fibrosis and collagen I/III synthesis in mice exposed to LPS for four weeks. Our results demonstrated that DEX effectively accelerated LPS-induced differentiation of CFs to myofibroblasts through the PKC-p38-Smad2/3 signaling pathway by activating α2A-AR.
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- 2021
5. Clinical Significance Of Linc00342 Expression In The Peripheral Blood Lymphocytes Of Patients With Chronic Kidney Disease
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Yaqian Xu, Cheng Liu, Qi Zou, and Xueping Wu
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medicine.medical_specialty ,business.industry ,Lymphocyte ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,medicine.disease ,Gastroenterology ,Confidence interval ,Peripheral blood ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Nephrology ,Internal medicine ,Peripheral blood lymphocyte ,medicine ,Biomarker (medicine) ,Clinical significance ,Inflammatory factors ,business ,Kidney disease - Abstract
Objective To investigate the expression of Linc00342 in peripheral blood lymphocytes in patients with chronic kidney disease (CKD) and healthy people and to identify Linc00342 as a biomarker of chronic kidney disease. Methods Peripheral blood samples were collected from 30 patients with chronic kidney disease and 10 healthy volunteers at the First Affiliated Hospital of Bengbu Medical College, China. According to CKD classification, the patients were divided into three CKD groups (the CKD1/2 group, CKD3/4 group and CKD5 group) and a healthy volunteer group (the H group). The relative expression of Linc00342 in lymphocytes was detected by RT-PCR, while the IL-6 and IL-10 levels in the serum were detected by ELISA. In addition, the general data of the patients and healthy volunteers were recorded. Finally, SPSS software was used for statistical analysis. Results The expression level of Linc00342 in the peripheral blood lymphocytes of the four groups increased significantly as the CKD grade increased, and there were statistically significant differences (p < 0.01). There was a positive linear correlation between the expression of Linc00342 in peripheral blood lymphocytes and the eGFR (p < 0.05), which was expressed by the linear model equation: Y = 2.532 + 0.012X. Among the inflammatory factors for the early diagnosis of CKD, the area under the ROC curve for the expression of Linc00342 in peripheral blood lymphocyte was 0.953, the standard error was 0.034 and the 95% confidence interval was 0.000-1.000. Conclusion The expression level of Linc00342 in peripheral blood lymphocytes can reflect the severity of CKD, and Linc00342 is possibly used as a molecular marker of CKD.
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- 2019
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6. Identification and integrated analysis of key differentially expressed circular RNAs in ER-positive subtype breast cancer
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Kai Yin, Shan Zhang, Jing Peng, Wenjin Yin, Yaohui Wang, Yaqian Xu, Rui Sha, Jinsong Lu, Chenwei Yuan, Xiaonan Sheng, Lei Zhang, Liheng Zhou, Shuguang Xu, and Yanping Lin
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Adult ,0301 basic medicine ,Cancer Research ,Microarray ,Estrogen receptor ,Breast Neoplasms ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Circular RNA ,Cell Line, Tumor ,microRNA ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,RNA, Messenger ,Neoplasm Metastasis ,Aged ,Neoplasm Staging ,Gene Expression Profiling ,Computational Biology ,Cancer ,RNA, Circular ,Middle Aged ,Prognosis ,Non-coding RNA ,medicine.disease ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Cell Transformation, Neoplastic ,030104 developmental biology ,Receptors, Estrogen ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Transcriptome ,Carcinogenesis - Abstract
Aim: To systematically profile and characterize the circular RNA (circRNA) expression pattern in estrogen receptor (ER)-positive breast cancer (BC). Materials & methods: CircRNA expression profile was performed in ER-positive BC and adjacent nontumor tissues. The differentially expressed circRNAs (DECs) was analyzed by bioinformatics. The analysis findings were validated by quantitative real-time PCR. Results: In total, 3653 DECs were detected in our ER-positive BC compared with the control. Bioinformatics analysis showed that some pathways related to cancer, especially BC, were significantly enriched. Additionally, hsa_circ_0087378 was validated to be downregulated in ER-positive BC and the hsa_circ_0087378-miR-1260b-SFRP1 axis was proposed to be a key regulatory pathway. Conclusion: This study revealed the general expression characteristics of specific DECs in ER-positive BC and hsa_circ_0087378 might be a promising candidate target.
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- 2019
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7. Predictive value of lncRNA LOC100505851 in breast cancer in the neoadjuvant setting
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Wenjin Yin, Shuguang Xu, Chenwei Yuan, Yaqian Xu, Rui Sha, Yaohui Wang, Xiaonan Sheng, Jinsong Lu, Ziping Wu, Yanping Lin, Jing Peng, and Liheng Zhou
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,Subcellular localization ,Long non-coding RNA ,Text mining ,Breast cancer ,Internal medicine ,medicine ,Immunohistochemistry ,Surgery ,Original Article ,business ,Pathological ,Neoadjuvant therapy - Abstract
BACKGROUND: The expression and function of long noncoding RNA (lncRNA) LOC100505851 in breast cancer are still unknown. We aimed to examine the expression of lncRNA LOC100505851 in breast cancer and adjacent tissues and preliminarily explore its predictive value and function in breast cancer patients receiving neoadjuvant therapy (NAT). METHODS: The expression of lncRNA LOC100505851 was tested by qRT-PCR. The correlation between LOC100505851 expression and clinicopathological factors as well as pathological complete response (pCR) was analyzed by chi-squared test and logistic regression, respectively. The online database Kaplan-Meier plotter (KM plotter) was used to compare relapse-free survival (RFS) and overall survival (OS) between groups with different LOC100505851 expression levels. Subcellular localization of LOC100505851 was determined by nuclear and cytoplasmic extraction. A bioinformatics tool was used to predict RNA-binding proteins (RBPs) and interaction among these proteins. RESULTS: LncRNA LOC100505851 was significantly expressed at lower levels in cancer tissues than in adjacent tissues (P
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- 2021
8. COVID-19 manifestations in people with Parkinson's disease: a USA cohort
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Serge Przedborski, Linn E. Katus, Sheng-Han Kuo, Joshua A. Halpern, Hiral Shah, Nora Vanegas-Arroyave, Matthew Surface, James C. Beck, Linda M. Winfield, Blair Ford, Amanda K. Chan, Stanley Fahn, Yaqian Xu, Roy N. Alcalay, Megan P. Feeney, Cheryl Waters, and Kimberly Tsu Kwei
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Pediatrics ,medicine.medical_specialty ,Parkinson's disease ,Movement disorders ,Population ,Anxiety ,Surveys and Questionnaires ,medicine ,Humans ,Risk factor ,education ,Depression (differential diagnoses) ,education.field_of_study ,Original Communication ,business.industry ,SARS-CoV-2 ,COVID-19 ,Parkinson Disease ,medicine.disease ,Neurology ,Dyskinesia ,Parkinson’s disease ,Chills ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Background With the explosion of COVID-19 globally, it was unclear if people with Parkinson’s disease (PD) were at increased risk for severe manifestations or negative outcomes. Objectives To report on people with PD who had suspected or confirmed COVID-19 to understand how COVID-19 manifested in PD patients. Methods We surveyed PD patients who reported COVID-19 to their Movement Disorders specialists at Columbia University Irving Medical Center and respondents from an online survey administered by the Parkinson’s Foundation that assessed COVID-19 symptoms, general clinical outcomes and changes in motor and non-motor PD symptoms. Results Forty-six participants with PD and COVID-19 were enrolled. Similar to the general population, the manifestations of COVID-19 among people with PD were heterogeneous ranging from asymptomatic carriers (1/46) to death (6/46). The most commonly reported COVID-19 symptoms were fever/chills, fatigue, cough, weight loss, and muscle pain. Worsening and new onset of motor and non-motor PD symptoms during COVID-19 illness were also reported, including dyskinesia, rigidity, balance disturbances, anxiety, depression, and insomnia. Conclusion We did not find sufficient evidence that PD is an independent risk factor for severe COVID-19 and death. Larger studies with controls are required to understand this further. Longitudinal follow-up of these participants will allow for observation of possible long-term effects of COVID-19 in PD patients. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10784-3.
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- 2021
9. Neo-Family History Score Is A Novel Biomarker of Pathological Complete Response, Safety, and Survival Outcomes In Patients With Breast Cancer Receiving Neoadjuvant Platinum-Based Chemotherapy: A Retrospective Analysis of Two Prospective Trials
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Jinsong Lu, Yaohui Wang, Shuguang Xu, Yifan Wu, Wenjin Yin, Jie Zhang, Yanping Lin, Yaqian Xu, Jing Peng, and Liheng Zhou
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Oncology ,medicine.medical_specialty ,business.industry ,Cancer ,Gene mutation ,medicine.disease ,Logistic regression ,Breast cancer ,Clinical research ,Internal medicine ,Medicine ,Biomarker (medicine) ,Family history ,business ,Estrogen Receptor Status - Abstract
Background: Homologous recombination repair gene mutations are associated with increased platinum-based chemosensitivity, whereas few studies have reported the predictive value of family history of cancer for breast cancer in the neoadjuvant setting. This study aimed to construct a brief and effective novel family history scoring system and explore its association with pathological complete response (pCR), survival outcomes, and safety for locally advanced breast cancer receiving platinum-based neoadjuvant chemotherapy. Methods: A total of 262 patients treated with neoadjuvant cisplatin and paclitaxel were included. Neo-Family History Score (NeoFHS) was calculated according to cancer type, age at diagnosis, kinship, and number of affected relatives. Logistic regression was performed to analyze the association between pCR and NeoFHS. Survival rates were compared by Kaplan-Meier curves, examined by log-rank test and Cox proportional hazard regressions. Results: For all patients enrolled in this study, clinical tumor stage (p=0·048), estrogen receptor status (p=0·001), progesterone receptor status (p=0·036), human epidermal growth factor receptor 2 (HER2) status (p=0·013), and molecular subtype (p=0·016) were significantly related to NeoFHS. The multivariate logistic regression revealed that NeoFHS is an independent predictive factor of pCR (OR=2·262, 95% CI 1·159-4·414, p=0·017), especially in node-positive (OR=3·088, 95% CI 1·498-6·367, p=0·002), hormone receptor-positive (OR=2·645, 95% CI 1·164-6·010, p=0·020), and HER2-negative subgroups (OR=4·786, 95% CI 1·550-14·775, p=0·006). Kaplan-Meier estimates suggested that NeoFHS could serve as an independent prognostic factor for relapse-free survival in the whole group (adjusted HR=0·305, 95% CI 0·102-0·910, p=0·033) and node-positive subgroup (adjusted HR=0·317, 95% CI 0·103-0·973, p=0·045). Furthermore, alopecia (p=0·001), nausea (p=0·001), peripheral neuropathy (p=0·018), diarrhea (p=0·026), constipation (p=0·037) of any grade and leukopenia of grade 3 or greater (p=0·005) were more common in patients with higher NeoFHS. Conclusions: Our study revealed that NeoFHS is a practical and effective biomarker for predicting not only pCR and survival outcomes but also chemotherapy-induced AEs for neoadjuvant platinum-based chemotherapy for breast cancer. It may help screen candidate responders and guide safety managements in the future. Trial Registrion: SHPD001 (ClinicalTrials.gov identifier: NCT02199418) and SHPD002 (ClinicalTrials.gov identifier: NCT02221999). Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Shanghai Natural Science Foundation [grant numbers 19ZR1431100], Clinical Research Plan of Shanghai Hospital Development Center [grant numbers SHDC2020CR3003A, 16CR3065B and 12016231], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Outstanding Youth Medical Talents [grant numbers 2018-15 and 2018-16], Shanghai Collaborative Innovation Center for Translational Medicine [grant number TM201908], Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University [grant numbers YG2017QN49 and ZH2018QNA42], Nurturing Fund of Renji Hospital [grant numbers PYMDT-002, PY2018-IIC-01 and PY2018-III-15], Science and Technology Commission of Shanghai Municipality [grant numbers 20DZ2201600 and 15JC1402700], and Shanghai Municipal Key Clinical Specialty Declaration of Interest: None to declare. Ethical Approval: Ethical approvals were granted for both trials by the Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University.
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- 2021
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10. Linc00665 Can Predict the Response to Cisplatin-Paclitaxel Neoadjuvant Chemotherapy for Breast Cancer Patients
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Rui Sha, Jinsong Lu, Fan Yang, Yanping Lin, Liheng Zhou, Shan Zhang, Wenjin Yin, Yaqian Xu, Jing Peng, Xiaonan Sheng, and Huijuan Dai
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Cancer Research ,Multivariate analysis ,medicine.medical_treatment ,Logistic regression ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Internal medicine ,medicine ,KEGG ,predictive biomarker ,Original Research ,Chemotherapy ,Univariate analysis ,Receiver operating characteristic ,long non-coding RNA ,business.industry ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Hormone receptor ,030220 oncology & carcinogenesis ,pathological complete response ,business ,neoadjuvant chemotherapy - Abstract
ObjectiveLinc00665 is a novel long non-coding RNA that can promote the progression of breast cancer, but its value in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer has not been reported. We aim to analyze the correlation between Linc00665 expression and pathological complete response (pCR) in breast cancer patients.Materials and MethodsThe present study examined the predictive role of Linc00665 expression in pCR after NAC using both univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the performance of Linc00665 in predicting pCR. The Kyoto Encyclopedia of Gene and Genome (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were also conducted to determine the biological processes where Linc00665 may participate in.ResultsThe present study study totally enrolled 102 breast cancer patients. The univariate analysis showed that Linc00665 level, human epidermal growth factor receptor 2 (HER2) status and hormone receptor (HR) status were correlated with pCR. The multivariate analysis showed that Linc00665 expression was an independent predictor of pCR (OR = 0.351, 95% CI: 0.125–0.936, P = 0.040), especially in patients with HR-positive/HER2-negative subtype (OR = 0.272, 95% CI: 0.104–0.664, P = 0.005). The KEGG analysis indicated that Linc00665 may be involved in drug metabolism. The GSEA analysis revealed that Linc00665 is correlated to DNA damage repair.ConclusionLinc00665 may be a potential novel predictive biomarker for breast cancer in NAC, especially for HR-positive/HER2-negative patients.
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- 2021
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11. Predictive and Prognostic Impact of Ferroptosis-Related Genes ACSL4 and GPX4 on Breast Cancer Treated With Neoadjuvant Chemotherapy
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Wenjin Yin, Xiaonan Sheng, Yaqian Xu, Yanping Lin, Jie Zhang, Jinsong Lu, Ziping Wu, Chenwei Yuan, Shuguang Xu, Liheng Zhou, Rui Sha, Jing Peng, and Yaohui Wang
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Oncology ,Medicine (General) ,Biopsy ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Logistic regression ,Breast cancer ,Antineoplastic Combined Chemotherapy Protocols ,Databases, Genetic ,Odds Ratio ,Original Research ,medicine.diagnostic_test ,General Medicine ,Middle Aged ,Prognosis ,Immunohistochemistry ,Neoadjuvant Therapy ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,Medicine ,Female ,Adult ,medicine.medical_specialty ,Specialty ,Breast Neoplasms ,Neoadjuvant chemotherapy ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,ACSL4 ,R5-920 ,Cell Line, Tumor ,Internal medicine ,Coenzyme A Ligases ,Biomarkers, Tumor ,medicine ,Humans ,Ferroptosis ,Pathological ,Aged ,Neoplasm Staging ,Chemotherapy ,Pathological complete response ,business.industry ,Translational medicine ,Computational Biology ,Phospholipid Hydroperoxide Glutathione Peroxidase ,medicine.disease ,Clinical research ,business ,GPX4 - Abstract
Background Recent evidence shows that inducing ferroptosis may improve efficacy of tumor therapy. However, ferroptosis-related genes have been little studied in patients with breast cancer especially in the neoadjuvant setting. ACSL4 and GPX4 have been well established as the positive and negative regulator of ferroptosis, respectively. This study aimed to explore the predictive value of ACSL4 and GPX4 for patients with breast cancer administered neoadjuvant chemotherapy. Methods This study included patients treated with paclitaxel-cisplatin-based neoadjuvant chemotherapy. Immunohistochemistry staining of ACSL4 and GPX4 was carried out on the core needle biopsy specimens. Logistic regression was performed to explore the predictive biomarkers of pathological complete response (pCR). Survival analyses were examined by log-rank test and Cox proportional hazard regression. Findings A total of 199 patients were included for the analyses. Both ACSL4 expression and ACSL4/GPX4 combination status could serve as independent predictive factors for pCR. The interaction for pCR was observed between ACSL4 and clinical tumor stage. Besides, ACSL4 expression, GPX4 expression, and their combination status were independent prognostic factors for disease-free survival. Analyses of the Kaplan-Meier Plotter database suggested that higher ACSL4 expression is related to better overall survival, and higher GPX4 expression is related to better distant metastasis-free survival. Pathway analyses revealed that ACSL4 and GPX4 might function in crucial pathways including apoptosis, autophagy, cell adhesion, lipid metabolism, etc. Interpretation This study revealed the critical value of ACSL4 and GPX4 serving as novel predictive and prognostic biomarkers for patients with breast cancer receiving neoadjuvant chemotherapy. It might be a novel strategy to induce ferroptosis to promote chemosensitivity. Future studies are required to elucidate the potential mechanisms. Funding This work was supported by Shanghai Natural Science Foundation [grant number 19ZR1431100], Clinical Research Plan of Shanghai Hospital Development Center [grant numbers SHDC2020CR3003A, 16CR3065B, and 12016231], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Youth Medical Talents - Specialist Program [grant number 2018-15], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Outstanding Youth Medical Talents [grant number 2018-16], Shanghai Collaborative Innovation Center for Translational Medicine [grant number TM201908], Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University [grant numbers YG2017QN49, ZH2018QNA42, and YG2019QNA28], Nurturing Fund of Renji Hospital [grant numbers PYMDT-002, PY2018-IIC-01, PY2018-III-15, and PYIII20-09], Science and Technology Commission of Shanghai Municipality [grant numbers 20DZ2201600 and 15JC1402700], and Shanghai Municipal Key Clinical Specialty.
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- 2021
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12. TIMELESS regulates sphingolipid metabolism and tumor cell growth through Sp1/ACER2/S1P axis in ER-positive breast cancer
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Jinsong Lu, Huijuan Dai, Pei-Qi Huang, Ziping Wu, Shu-Heng Jiang, Zhigang Zhang, Xueli Zhang, Qing Li, Jing Peng, Wenjin Yin, Yaqian Xu, Li-Peng Hu, Huizhen Nie, and Shan Zhang
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Cancer Research ,Timeless ,Sp1 Transcription Factor ,Biopsy ,Immunology ,Regulator ,Estrogen receptor ,Mice, Nude ,Breast Neoplasms ,Cell Cycle Proteins ,Article ,Pathogenesis ,Cellular and Molecular Neuroscience ,Mice ,Breast cancer ,Downregulation and upregulation ,Sphingosine ,Cell Line, Tumor ,Medicine ,Animals ,Humans ,lcsh:QH573-671 ,skin and connective tissue diseases ,Cell Proliferation ,Sphingolipids ,lcsh:Cytology ,Cell growth ,business.industry ,Intracellular Signaling Peptides and Proteins ,Cancer ,Cell Biology ,medicine.disease ,Xenograft Model Antitumor Assays ,Cancer metabolism ,Mitochondria ,Gene Expression Regulation, Neoplastic ,Gene Knockdown Techniques ,Cancer research ,Alkaline Ceramidase ,Female ,Lysophospholipids ,business - Abstract
Breast cancer is one of the most common female malignant cancers. Biorhythm disorder largely increases the risk of breast cancer. We aimed to investigate the biological functions and molecular mechanisms of circadian gene TIMELESS circadian regulator (TIM) in estrogen receptor (ER)-positive breast cancer and provide a new therapeutic target for breast cancer patients. Here, we explored that the expression of TIM was elevated in breast cancer, and high expression of TIM in cancer tissues was associated with poor prognosis, especially in the ER-positive breast cancer patients. In addition, we found that TIM promoted cell proliferation and enhanced mitochondrial respiration. TIM interacted with specificity protein 1 (Sp1) which contributes to upregulate the expression of alkaline ceramidase 2 (ACER2). Moreover, ACER2 is responsible for TIM-mediated promotive effects of cell growth and mitochondrial respiration. Collectively, our research unveiled a novel function of TIM in sphingolipid metabolism through interaction with Sp1. It provides a new theoretical explanation for the pathogenesis of breast cancer, and targeting TIM may serve as a potential therapeutic target for ER-positive breast cancer.
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- 2020
13. TIMELESS Regulates Sphingolipid Metabolism and Tumor Cell Growth Through Sp1/ACER2/S1P Axis in ER-Positive Breast Cancer
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Ziping Wu, Li-Peng Hu, Shu-Heng Jiang, Xueli Zhang, Zhigang Zhang, Pei-Qi Huang, Jing Peng, Wenjin Yin, Huijuan Dai, Yaqian Xu, Jinsong Lu, Shan Zhang, and Qing Li
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Breast cancer ,Downregulation and upregulation ,Cell growth ,business.industry ,Timeless ,Cancer research ,medicine ,Estrogen receptor ,Institutional Animal Care and Use Committee ,Cancer ,medicine.disease ,business ,Chromatin immunoprecipitation - Abstract
Background: Breast cancer is one of the most common female malignant cancers. Biorhythm disorder largely increases the risk of breast cancer. We aimed to investigate the biological functions and molecular mechanisms of circadian gene TIMELESS circadian regulator (TIM) in estrogen receptor (ER)-positive breast cancer and provide a new therapeutic target for breast cancer patients. Methods: The concentration of sphingosine 1-phosphate (S1P) was detected by high-performance liquid chromatography-tandem mass spectrometry. The Oxygen consumption rate was measured by XF96 metabolic flux analyzer. The interaction between TIM and Specificity protein 1 (Sp1) was confirmed by Co-immunoprecipitation. Chromatin immunoprecipitation and luciferase report assay were performed to demonstrate whether SP1 binds on the Alkaline Ceramidase 2 (ACER2) promotor. Findings: The expression of TIM was elevated in breast cancer, and high expression of TIM in cancer tissues was associated with poor prognosis, especially in the ER-positive breast cancer patients. In addition, we found that TIM promoted cell proliferation and enhanced mitochondrial respiration. TIM interacted with Sp1 which contributes to upregulate the expression of ACER2. Moreover, ACER2 is responsible for TIM-mediated promotive effects of cell growth and mitochondrial respiration. Interpretation: Our research unveiled a novel function of TIM in sphingolipid metabolism through interaction with Sp1. It provides a new theoretical explanation for the pathogenesis of breast cancer, and targeting TIM may serve as a potential therapeutic target for ER-positive breast cancer. Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 81672358, No. 81802890, No. 81172505, No. 81302302). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The SHPD001 and SHPD002 trials were approved by the Independent Ethical Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University. Before enrollment, all patients signed written informed consent. All animal experiments were approved by the Institutional Animal Care and Use Committee of East China Normal University.
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- 2020
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14. Association of Neo-Family History Score with pathological complete response, safety, and survival outcomes in patients with breast cancer receiving neoadjuvant platinum-based chemotherapy: An exploratory analysis of two prospective trials
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Liheng Zhou, Wenjin Yin, Yaohui Wang, Yifan Wu, Yaqian Xu, Jie Zhang, Yanping Lin, Jinsong Lu, Shuguang Xu, and Jing Peng
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Oncology ,Medicine (General) ,medicine.medical_specialty ,business.industry ,Nausea ,Specialty ,Cancer ,General Medicine ,medicine.disease ,Neo-Family History Score ,breast cancer ,R5-920 ,Clinical research ,Breast cancer ,Internal medicine ,pathological complete response ,medicine ,platinum ,Family history ,medicine.symptom ,Adverse effect ,business ,Estrogen Receptor Status ,Research Paper ,neoadjuvant chemotherapy - Abstract
Background Homologous recombination deficiency is associated with platinum-based chemosensitivity, whereas few studies reported the predictive value of family history of cancer for breast cancer in the neoadjuvant setting. This study aimed to construct a novel family history scoring system and to explore its association with clinical outcomes for patients with breast cancer receiving neoadjuvant platinum-based chemotherapy. Methods This study included 262 patients with locally advanced breast cancer enrolled in the SHPD001 and SHPD002 trials from October 2013 to June 2018. The Neo-Family History Score (NeoFHS) was calculated according to cancer type, age at diagnosis, kinship, and number of affected relatives. Findings Clinical tumor stage (p=0·048), estrogen receptor status (p=0·001), progesterone receptor status (p=0·036), human epidermal growth factor receptor 2 status (p=0·013), and molecular subtype (p=0·016) were significantly related to NeoFHS. NeoFHS could serve as an independent predictive factor of pathological complete response (pCR) (OR=2·262, 95% CI 1·159-4·414, p=0·017) and an independent prognostic factor of relapse-free survival (adjusted HR=0·305, 95% CI 0·102-0·910, p=0·033). Alopecia (p=0·001), nausea (p=0·001), peripheral neuropathy (p=0·018), diarrhea (p=0·026), constipation (p=0·037) of any grade and leukopenia of grade 3 or greater (p=0·005) were more common in patients with higher NeoFHS. Interpretation NeoFHS is a practical and effective biomarker for predicting not only pCR and survival outcomes but also chemotherapy-induced adverse events for neoadjuvant platinum-based chemotherapy in breast cancer. It may help screen candidate responders and guide safety managements. Funding Shanghai Natural Science Foundation [grant number 19ZR1431100], Clinical Research Plan of Shanghai Hospital Development Center [grant numbers SHDC2020CR3003A, 16CR3065B, and 12016231], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Youth Medical Talents - Specialist Program [grant number 2018-15], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Outstanding Youth Medical Talents [grant number 2018-16], Shanghai Collaborative Innovation Center for Translational Medicine [grant number TM201908], Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University [grant numbers YG2017QN49, ZH2018QNA42, and YG2019QNA28], Nurturing Fund of Renji Hospital [grant numbers PYMDT-002, PY2018-IIC-01, PY2018-III-15, and PYIII20-09], Science and Technology Commission of Shanghai Municipality [grant numbers 20DZ2201600 and 15JC1402700], and Shanghai Municipal Key Clinical Specialty.
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- 2021
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15. Serum uric acid levels and freezing of gait in Parkinson’s disease
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Huifang Shang, Ruwei Ou, Yaqian Xu, Wei Song, Qianqian Wei, Yanbing Hou, Bi Zhao, and Bei Cao
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Male ,0301 basic medicine ,medicine.medical_specialty ,Levodopa ,Neurology ,Parkinson's disease ,Dermatology ,Logistic regression ,Severity of Illness Index ,Gastroenterology ,Body Mass Index ,Antiparkinson Agents ,03 medical and health sciences ,chemistry.chemical_compound ,Cognition ,Sex Factors ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Mass index ,Gait ,Montreal Cognitive Assessment ,Parkinson Disease ,Fasting ,General Medicine ,Middle Aged ,Mental Status and Dementia Tests ,medicine.disease ,Uric Acid ,Surgery ,Psychiatry and Mental health ,Cross-Sectional Studies ,Logistic Models ,030104 developmental biology ,chemistry ,Dyskinesia ,Disease Progression ,Uric acid ,Female ,Neurology (clinical) ,medicine.symptom ,Psychology ,Biomarkers ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Uric acid (UA) is a natural antioxidant and iron scavenger in the human body, which has been hypothesized to exert an anti-oxidative effect in Parkinson’s disease (PD). This study aimed to investigate the relationship between serum UA levels and freezing of gait (FOG) in PD. A total of 321 Chinese PD patients with fasting serum UA evaluated were included in the cross-sectional study. Demographics, clinical features, and therapeutic regimen were collected. The Unified PD Rating Scale (UPDRS) III and Hoehn and Yahr (H and Y) stage were used to evaluate the severity of disease, and the Frontal Assessment Battery (FAB) and Montreal Cognitive Assessment (MoCA) scales were used to assess the cognitive function. Patients with FOG showed lower proportion of male, longer disease duration, lower body mass index, lower concentrations of serum UA, higher total levodopa equivalent daily dosage, higher UPDRS III score, greater median H and Y stage, lower scores of FAB and MoCA, and higher frequencies of motor fluctuation, dyskinesia, falls, and festination compared to patients without FOG (P
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- 2017
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16. Novel lymphocyte to red blood cell ratio (LRR), neutrophil to red blood cell ratio (NRR), monocyte to red blood cell ratio (MRR) as predictive and prognostic biomarkers for locally advanced breast cancer
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Haofeng Wang, Jinsong Lu, Xiaonan Sheng, Yanping Lin, Rui Sha, Liheng Zhou, Wenjin Yin, Yaohui Wang, and Yaqian Xu
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Oncology ,medicine.medical_specialty ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Monocyte ,Lymphocyte ,0206 medical engineering ,Therapeutic effect ,02 engineering and technology ,medicine.disease ,Logistic regression ,020601 biomedical engineering ,Red blood cell ,medicine.anatomical_structure ,Breast cancer ,Internal medicine ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,020201 artificial intelligence & image processing ,Surgery ,Original Article ,business ,Neoadjuvant therapy - Abstract
Background: Lymphocytes, neutrophils, and monocytes are vital effector cells in innate immunity. We postulated that lymphocyte to red blood cell ratio (LRR), neutrophil to red blood cell ratio (NRR), monocyte to red blood cell ratio (MRR) could represent the intensity of systemic inflammatory immunological reaction reflected through the lymphocyte, neutrophil and monocyte respectively. This study aimed to access the predictive and prognostic value of LRR, NRR, MRR and LRR-NRR-MRR score for locally advanced breast cancer. Methods: A total of 137 patients from two clinical trials SHPD002 and SHPD003 were included. Logistic regression analysis was used to evaluate the association between ratios and pathological complete response (pCR). Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and cox regression analysis. Results: Lower LRR-NRR-MRR score (OR =0.593; 95% CI: 0.369–0.954; P=0.031) was more easily to achieve pCR in multivariate analysis. Lower LRR (P=0.022), NRR (P=0.027) and MRR (P=0.024) were significantly associated with better DFS. LRR-NRR-MRR score was an independently prognostic factor for both DFS (HR =3.318; 95% CI: 1.601–6.876; P=0.001) and OS (HR =3.160; 95% CI: 1.030–9.696; P=0.044). Conclusions: The LRR-NRR-MRR score could be identified as a new predictive biomarker for the therapeutic effect of neoadjuvant therapy and an independent prognostic factor for both DFS and OS for locally advanced breast cancer.
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- 2019
17. SLC1A2 rs3794087 are associated with susceptibility to Parkinson's disease, but not essential tremor, amyotrophic lateral sclerosis or multiple system atrophy in a Chinese population
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Yongping Chen, Jing Yang, Bei Cao, Yaqian Xu, Bi Zhao, Huifang Shang, Qianqian Wei, Wei Song, and Ruwei Ou
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Adult ,Male ,0301 basic medicine ,China ,medicine.medical_specialty ,Pathology ,Parkinson's disease ,Genotype ,Essential Tremor ,Polymorphism, Single Nucleotide ,Severity of Illness Index ,Gastroenterology ,Cohort Studies ,Glutamate Plasma Membrane Transport Proteins ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,Gene Frequency ,Internal medicine ,parasitic diseases ,Genetic model ,medicine ,Humans ,Genetic Predisposition to Disease ,Amyotrophic lateral sclerosis ,Allele ,Allele frequency ,Aged ,Essential tremor ,business.industry ,Amyotrophic Lateral Sclerosis ,Parkinson Disease ,Middle Aged ,Multiple System Atrophy ,medicine.disease ,Minor allele frequency ,030104 developmental biology ,Excitatory Amino Acid Transporter 2 ,Neurology ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Background The association between the polymorphism rs3794087 in the solute carrier family 1, member 2 ( SLC1A2 ) and the risk of essential tremor (ET) among different studies is controversial. Considering the overlap of the clinical manifestations and pathological characteristics of ET, Parkinson's disease (PD), multiple system atrophy (MSA), as well as amyotrophic lateral sclerosis (ALS), we explored the possible genetic association of rs3794087 with ET, PD, MSA and ALS in a Chinese cohort. Methods A total of 112 ET, 621 PD, 356 MSA, 513 sporadic ALS (SALS) patients and 437 healthy controls (HCs) were genotyped for rs3794087 using the Sequenom iPLEX Assay technology. Results Significant association was found between SLC1A2 rs3794087 and PD in the additive model ( p = 0.006), which was more obvious in early onset PD. The minor allele of rs3794087 decreased the risk for early onset PD ( p = 0.011, OR: 0.73, 95% CI: 0.56–0.94). However, no significant differences in the genotype distributions and allele frequency were observed in the allelic, additive, dominant or recessive genetic models of SLC1A2 rs3794087 between ET patients and HCs, between SALS patients and HCs, and between MSA and HCs. Conclusions Our results suggested SLC1A2 rs3794087 may decrease the risk for PD in a Chinese cohort, but do not support a role in the susceptibility to SALS or MSA.
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- 2016
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18. No association of GPNMB rs156429 polymorphism with Parkinson’s disease, amyotrophic lateral sclerosis and multiple system atrophy in Chinese population
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Huifang Shang, Yongping Chen, Ruwei Ou, YaQian Xu, Qianqian Wei, Ke Chen, and Bei Cao
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Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pathology ,Genome-wide association study ,Polymorphism, Single Nucleotide ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,Gene Frequency ,Internal medicine ,mental disorders ,parasitic diseases ,medicine ,Humans ,Genetic Predisposition to Disease ,Amyotrophic lateral sclerosis ,Allele frequency ,Genetic Association Studies ,Aged ,Genetic association ,Membrane Glycoproteins ,GPNMB ,business.industry ,General Neuroscience ,Amyotrophic Lateral Sclerosis ,Parkinson Disease ,Middle Aged ,Multiple System Atrophy ,medicine.disease ,Minor allele frequency ,030104 developmental biology ,Case-Control Studies ,Female ,Age of onset ,business ,030217 neurology & neurosurgery - Abstract
Background The rs156429 polymorphism in the glycoprotein nonmetastatic melanoma protein B (GPNMB) gene was found to be associated with the risk for Parkinson disease (PD) in Caucasian population by genome-wide association studies (GWAS). Recently, encoded protein, GPNMB, was identified as a novel neuro-protective factor in amyotrophic lateral sclerosis (ALS). The overlapping of clinical manifestations and pathologic characteristics among PD, ALS, and multiple system atrophy (MSA) are observed. Object This study aimed at investigating the possible associations of the polymorphism and the three neurodegenerative diseases: PD, ALS and MSA in a Chinese population. Methods All of the subjects, including PD (n = 1096), sporadic ALS (SALS) (n = 876) and MSA (n = 356) patients, and 829 health controls (HCs) were included. All subjects were genotyped for this polymorphism using Sequenom iPLEX Assay technology. Results No differences were found in the genotype distributions and minor allele frequency of GPNMB rs156429 between PD patients and HCs, between SALS patients and HCs, between MSA patients and HCs, and between subgroups of PD, ALS and MSA patients with regard to clinical features such as sex, age of onset, presence or absence of cognitive abnormality, depression and anxiety. Conclusion Lack of association identified in our study suggests that it may be premature to conclude associations between GPNMB rs156429 and SALS, PD and MSA. More studies on such an association involving a larger number of participants are needed to confirm the present findings.
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- 2016
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19. Predictive and prognostic value of EPIC1 in patients with breast cancer receiving neoadjuvant chemotherapy
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Jie Zhang, Huijuan Dai, Wenjin Yin, Yaqian Xu, Yaohui Wang, Yanping Lin, Shan Zhang, Chenwei Yuan, Rui Sha, Xiaonan Sheng, Jinsong Lu, Liheng Zhou, Yan Wang, and Shuguang Xu
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Oncology ,medicine.medical_specialty ,Chemotherapy ,long non-coding RNA ,Cell growth ,business.industry ,medicine.medical_treatment ,RNA ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,lcsh:RC254-282 ,Long non-coding RNA ,breast cancer ,Breast cancer ,Apoptosis ,Internal medicine ,medicine ,biomarker ,Biomarker (medicine) ,In patient ,EPIC1 ,business ,Original Research ,neoadjuvant chemotherapy - Abstract
Background: EPIC1 is an oncogenic long non-coding ribonucleic acid (RNA) that promotes cell growth and cell-cycle progression and inhibits apoptosis in several cancer cell lines. However, clinical studies on EPIC1 in breast cancer, specifically in the neoadjuvant setting, are relatively few. Methods: Patients treated with weekly paclitaxel–cisplatin-based neoadjuvant chemotherapy after core-needle biopsy were included in the study. Real-time quantitative polymerase chain reaction assays were performed to detect EPIC1 expression. Results: Among all patients included in this study ( n = 111), higher EPIC1 expression was associated with estrogen receptor negativity, human epidermal growth factor receptor 2 positivity, higher Ki67 index, and higher histologic grade. Multivariate analysis suggested that EPIC1 expression was an independent predictive factor for pathological complete response, with a significant interaction between EPIC1 expression and age. The Kaplan–Meier Plotter dataset suggested that the EPIC1 high-expression group showed a worse 10-year distant metastasis-free survival and post-progression survival when compared with the EPIC1 low-expression group. The Cancer Genome Atlas dataset suggested that the overall survival in the EPIC1 high-expression group was inferior to that in the EPIC1 low-expression group, specifically in hormone receptor (HorR)-positive patients and patients aged Conclusions: Our study suggests that EPIC1 may be a promising biomarker for both neoadjuvant chemosensitivity and long-term clinical outcomes in breast cancer, specifically in the HorR-positive premenopausal subgroup. It may also help identify candidate responders and determine treatment strategies.
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- 2020
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20. Abstract 138: How Far is Too Far? A Decision Analysis Model of Pre-hospital Triage for Potential Large Vessel Occlusion Acute Stroke Patients
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Neal S. Parikh, Mitchell S.V. Elkind, Amelia K. Boehme, Joshua Z. Willey, Yaqian Xu, and Boshen Jiao
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Advanced and Specialized Nursing ,medicine.medical_specialty ,business.industry ,Health services research ,medicine.disease ,Triage ,Emergency medicine ,Medicine ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Stroke ,Decision analysis ,Large vessel occlusion ,Acute stroke - Abstract
Background and Purpose: We sought to determine when transporting patients directly to a comprehensive stroke center (CSC; the “mothership”) is favorable compared to a “drip-and-ship” approach while accounting for the varying predictive abilities of pre-hospital large vessel occlusion (LVO) screening methods. Methods: We built a decision analysis model to compare anticipated functional outcomes for patients who are within IV-tPA treatment window in “mothership” and “drip-and-ship”. Key branches included IV-tPA eligibility, IV-tPA only or endovascular therapy (ET), successful reperfusion after ET, and treatment effects. In terms of the probability of requiring ET, we assessed three pre-hospital LVO screening methods: no LVO screening, the Rapid Arterial oCclusion Evaluation (RACE) Scale for Stroke, and in-ambulance CT angiography for LVO. Good outcome was defined as mRS 0-1 and, secondarily, mRS 0-2. Imputed probabilities and workflow times were extracted from published studies. We used one-way and two-way sensitivity analyses to vary two key inputs: time from onset to arrival at primary stroke center (PSC) and additional travel time to CSC. Results: The relative benefit of the “mothership” approach varied with the likelihood of pre-hospital LVO identification for outcome of mRS 0-1. In the absence of pre-hospital LVO screening, “drip-and-ship” was always favored. When pre-hospital CT angiography is used, “mothership” is always favored. When modeling the use of the RACE Scale for patients with onset-to-PSC arrival time less than 70 minutes, “mothership” was favored if the additional travel time to CSC was less than 21 minutes. When onset-to-PSC arrival time passed 70 minutes, “mothership” was favored for additional travel times up to 48 minutes (Figure). Conclusion: The results of our decision analysis model suggest that, in addition to transport times, pre-hospital LVO screening and time from stroke onset could influence triage decision making.
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- 2018
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21. Analysis of SOD1 mutations in a Chinese population with amyotrophic lateral sclerosis: a case-control study and literature review
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Yongping Chen, Ruwei Ou, Huifang Shang, Yaqian Xu, Bei Cao, Jing Yang, Qianqian Wei, and Qingqing Zhou
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Adult ,Male ,0301 basic medicine ,Mutation rate ,Adolescent ,Genotype ,SOD1 ,Mutation, Missense ,Biology ,medicine.disease_cause ,Article ,03 medical and health sciences ,symbols.namesake ,Superoxide Dismutase-1 ,0302 clinical medicine ,parasitic diseases ,medicine ,Humans ,Missense mutation ,Genetic Predisposition to Disease ,Mutation frequency ,Amyotrophic lateral sclerosis ,Aged ,Genetics ,Sanger sequencing ,Mutation ,Multidisciplinary ,Amyotrophic Lateral Sclerosis ,Case-control study ,Exons ,Middle Aged ,medicine.disease ,030104 developmental biology ,symbols ,Female ,030217 neurology & neurosurgery - Abstract
Although the copper/zinc superoxide dismutase-1 (SOD1) gene has been identified in both familial ALS (FALS) and sporadic ALS (SALS), it has rarely been studied in Chinese patients with ALS, and there are few studies with large samples. This study sought to assess the prevalence of SOD1 mutations in Chinese ALS patients. We screened a cohort of 499 ALS patients (487 SALS and 12 FALS) from the Department of Neurology at the West China Hospital of Sichuan University and analyzed all coding exons of SOD1 by Sanger sequencing. In addition, we reviewed the mutation frequencies of common ALS causative genes in Chinese populations. Eight missense mutations in SOD1 were found in 8 ALS individuals: two novel mutations (p.G73D and p.V120F) and six previously reported mutations. The frequencies of SOD1 mutations were 1.03% (5/487) in SALS and 25% (3/12) in FALS from Southwest China. A literature review indicated that the mutation rates of major ALS causative genes were 53.55% in FALS and 6.29% in SALS. In Chinese SALS and FALS, the highest mutation frequency was in the SOD1 gene. Our results suggest that SOD1 mutation is the most common cause of ALS in Chinese populations and that the mutation spectrum of ALS varies among different ethnic populations.
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- 2017
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22. Meta-analysis of risk factors for Parkinson’s disease dementia
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Huifang Shang, Jing Yang, and Yaqian Xu
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0301 basic medicine ,medicine.medical_specialty ,Cognitive Neuroscience ,Population ,Review ,REM sleep behavior disorder ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Internal medicine ,mental disorders ,medicine ,Dementia ,education ,education.field_of_study ,Predictors ,business.industry ,Odds ratio ,medicine.disease ,Confidence interval ,nervous system diseases ,030104 developmental biology ,Risk factors ,Meta-analysis ,Relative risk ,Parkinson’s disease ,Neurology (clinical) ,Age of onset ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Background Parkinson’s disease (PD) is a common heterogeneous neurodegenerative disorder in elder population. Parkinson’s disease dementia (PDD) is one of the most common non-motor manifestations in PD patients. No comprehensive review has been conducted to assess risk factors for PDD. Methods A systemic search for studies on PDD risk factors was performed. Cohort and case–control studies that clearly defined PDD and presented relevant data were included. The data were analyzed to generate a pooled effect size and 95 % confidence interval (CI). Publication bias was assessed using the Egger’s test and the Begg’s test. Results A systematic search was conducted and yielded 5195 articles. After screening, 25 studies were included in the current analysis. Development of PDD was positively associated with age (odds ratio [OR] 1.07, 95 % CI 1.03-1.13), male (OR 1.33, 95 % CI 1.08-1.64), higher Unified Parkinson’s Disease Rating Scale (UPDRS) part III scores (relative risk [RR] 1.04, 95 % CI 1.01-1.07), hallucination (OR 2.47, 95 % CI 1.36-4.47), REM sleep behavior disorder (RBD) (OR 8.38, 95 % CI 3.87-18.08), smoking (ever vs. never) (RR 1.93, 95 % CI 1.15-3.26) and hypertension (OR 1.57, 95 % CI 1.11-2.22). An inverse association was found between education (RR 0.94, 95 % CI 0.91-0.98) and PDD. Other reported factors, including age of onset, disease duration of PD, Hoehn and Yahr stage and diabetes mellitus were not significantly associated with PDD. Conclusions Advanced age, male, higher UPDRS III scores, hallucination, RBD, smoking and hypertension increase the risk of PDD, whereas higher education is a protective factor for PDD. Electronic supplementary material The online version of this article (doi:10.1186/s40035-016-0058-0) contains supplementary material, which is available to authorized users.
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