1.Modulation of synaptic damage by Bushen Tiansui Decoction via the PI3K signaling pathway in an Alzheimer’s disease model
HUI Shan ; ZHENG Qing ; LI Hongli ; ZHU Lemei ; WU Beibei ; LIANG Lihui ; YANG Jingjing
Digital Chinese Medicine 2024;7(3):284-293
		                        		
		                        			Methods:
		                        			 (i) Animal experiments. This study conducted experiments using specific pathogen-free (SPF) grade male C57BL/6J wild-type (WT) mice and APP/PS1 double transgenic mice. The animals were divided into three groups: WT group (WT mice, n = 5, receiving distilled water daily), APP/PS1 group (APP/PS1 double transgenic mice, n = 5, receiving distilled water daily), and BSTSD group [APP/PS1 double transgenic mice, n = 5, treated with BSTSD suspension at a dosage of 27 g/(kg·d) for 90 d]. Cognitive function was assessed using the Morris water maze (MWM). Post-experiment, hippocampal tissues were collected for analysis of pyramidal cell and synaptic morphology through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). (ii) Cell experiments. The HT-22 cells were divided into control group (untreated), Aβ25-35 group (treated with 20 μmol/L Aβ25-35 for 24 h), icariin group (pre-treated with 20 μmol/L icariin for 60 min, followed by 20 μmol/L Aβ25-35 for an additional 24 h), and icariin + LY294002 group [treated with 20 μmol/L icariin and 20 μmol/L LY294002 (an inhibitor of the phosphoinostitide 3-kinases (PI3K) signaling pathway) for 60 min, then exposed to 20 μmol/L Aβ25-35 for 24 h], and cell viability was measured. Western blot was used to detect the expression levels of synapse-associated proteins [synaptophysin (SYP) and postsynaptic density-95 (PSD-95)] and PI3K signaling pathway associated proteins [phosphorylated (p)-PI3K/PI3K, p-protein kinase B (Akt)/Akt, and p-mechanistic target of rapamycin (mTOR)/mTOR]. 
		                        		
		                        			Results:
		                        			  (i) Animal experiments. Compared with APP/PS1 group, BSTSD group showed that escape latency was significantly shortened (P < 0.01) and the frequency of crossing the original platform was significantly increased (P < 0.01). Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly, nuclear staining was uniform, and vacuole-like changes were reduced after BSTSD treatment. TEM showed that the length of synaptic active zone in BSTSD treatment group was increased compared with APP/PS1 group (P < 0.01), and the width of synaptic gap was decreased (P < 0.01). (ii) Cell experiments. Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20 μmol/L (P > 0.05), and alleviated the cell viability decline induced by Aβ25-35 (P < 0.01). Western blot results showed that compared with Aβ25-35 group, the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly increased (P < 0.01), while the protein expression levels of SYP and PSD-95 were increased (P < 0.01). These effects were blocked by LY294002 (P < 0.01). 
		                        		
		                        			Conclusion
		                        			BSTSD and icariin enhance cognitive function and synaptic integrity in AD models and provide potential therapeutic strategies through activation of the PI3K/Akt/mTOR pathway. 
		                        		
		                        		
		                        		
		                        	
2.Clinical characteristics and prognostic factors of 145 patients with drug-induced liver injury
Hongli DU ; Xu LI ; Xuechun SHAN ; Yunying HU ; Leilei BAO ; Hui WANG
Academic Journal of Naval Medical University 2024;45(10):1259-1265
		                        		
		                        			
		                        			Objective To explore the clinical characteristics of patients with drug-induced liver injury(DILI),so as to provide references for its diagnosis and treatment.Methods The clinical data of inpatients diagnosed as DILI in The Third Affiliated Hospital of Naval Medical University(Second Military Medical University),from Jan.2017 to Dec.2021 were retrospectively analyzed,including basic information,underlying diseases,drug use history,clinical manifestations,laboratory indexes,severity and prognosis of DILI.Results Among 145 patients with DILI,112 cases(77.24%)were hepatocellular type,25 cases(17.24%)were cholestatic type,and 8 cases(5.52%)were mixed type.The types of drugs causing DILI mainly included traditional Chinese medicine,proprietary Chinese medicine and anti-infective drugs,and the proportions were 48.72%(76/156),16.03%(25/156),and 10.26%(16/156),respectively.The common clinical manifestations of DILI patients were jaundice(76.55%),poor appetite(52.41%),and fatigue(49.66%).The levels of alanine transaminase(ALT),aspartate transaminase,alkaline phosphatase(ALP),total bilirubin(TBil),γ-glutamyl transferase and albumin(ALB),as well as the length of hospital stay and severity distribution were significantly different among different types of liver injury(all P<0.05).The levels of ALT and ALB in the good prognosis group were significantly higher than those in the poor prognosis group,while the levels of TBil and international normalized ratio in the good prognosis group were significantly lower than those in the poor prognosis group(all P<0.05).Multivariate analysis showed that INR was an independent predictor of the prognosis of DILI(P<0.05).Conclusion Serum biochemistry indicators can help to identify the clinical classification and prognosis of DILI.Traditional Chinese medicine,proprietary Chinese medicine and other drugs can cause DILI.Medical staff should pay attention to it and strengthen public health education.
		                        		
		                        		
		                        		
		                        	
3.Research on clinical application of urine sediment score in the diagnosis of acute kidney injury
Hui ZHANG ; Wei XU ; Linlin QU ; Chunhe ZHAO ; Hongli SHAN ; Qin ZHANG ; Hongchen GAO ; Wenrui SUN ; Lina ZHU ; Yue ZHANG ; Xin YAN ; Xiaoquan YANG ; Wanning WANG ; Dong ZHANG ; Yao FU ; Xu ZHAO ; Liang HE
Chinese Journal of Laboratory Medicine 2024;47(5):548-553
		                        		
		                        			
		                        			Objective:To evaluate the clinical application of urine sediment score (USS) in early diagnosis, etiological differentiation, staging and prognosis of acute kidney injury (AKI), and to investigate the diagnostic efficacy of independent USS and its combination with blood urea nitrogen(Bun) serum creatinine(sCr) and uric acid(UA) in AKI.Methods:From August 23 to September 28, 2023, 9 020 morning urine samples of hospitalized patients in the First Hospital of Jilin University were detected by Sysmex UF5000.A total of 3 226 ssamples with small and round cell (SRC) > 1/μl and/or CAST>1/μl were screened for microscopic examination, and 404 cases with positive renal tubular epithelial cells and/or cast were enrolled in this study. There were 218 males and 186 females, aged 59.5 (49.0, 71.0) years. The 404 cases were divided into the USS AKI group (345 cases) and the USS non-AKI group (59 cases) according to the USS results based on the microscopic findings. According to Kidney Disease: Improving Global Outcomes (KDIGO) criteria, they were divided into KDIGO criteria AKI group (63 cases) and KDIGO criteria non-AKI group (341 cases), and the AKI group was divided into renal AKI group (33 cases) and non-renal AKI group (30 cases). According to the clinical diagnosis recorded in the medical records, they were divided into clinically diagnosed AKI group (29 cases) and clinically diagnosed non-AKI group (375 cases).The χ 2 test or Fisher exact test was used to compare USS in different AKI causes and stages. Logistic regression was used to calculate the odds ratio of renal AKI and stage 3 AKI. The area under the receiver operating characteristic curve was used to evaluate the sensitivity and specificity of USS, sCr, UA and Bun alone and in combination in the diagnosis of AKI, and the best cut-off value, sensitivity and specificity in the diagnosis of AKI were calculated. P < 0.05 was considered statistically significant. Results:The USS was used to identify the etiology of KDIGO standard AKI group,and there were significant differences in USS between renal AKI group and non-renal AKI group (χ 2=11.070, P<0.001). Compared to USS=1, the odds ratio of renal AKI was 8.125 when USS≥2 (95% CI 2.208—29.901). There was a statistically significant difference in the comparison of USS between groups in each stage of the AKI staging study based on USS (χ 2=15.724, P<0.05). Compared to USS=1, the odds ratio of stage 3 AKI was 9.714 when USS≥2 (95% CI 1.145-82.390). The AUC of independent USS in the diagnosis of AKI was 0.687 (95% CI 0.618-0.757, P<0.001), the specificity was 65.7% and the sensitivity was 61.9%. The AUC of USS combined with Bun, sCr, UA in the diagnosis of AKI was 0.794 (95% CI 0.608-0.980, P<0.05), the specificity was 82.4%, and the sensitivity was 88.9%. Conclusions:There wasan increased likelihood of renal AKI or stage 3 AKI while USS≥2,and whose combination with Bun, sCr and UA will improve the diagnostic efficiency of AKI.
		                        		
		                        		
		                        		
		                        	
4.Risk factors of linezolid-related thrombocytopenia in patients in the department of hepatobiliary surgery
Xuechun SHAN ; Xu LI ; Hongli DU ; Leilei BAO ; Hui WANG
Journal of Pharmaceutical Practice 2023;41(11):694-699
		                        		
		                        			
		                        			Objective To provide the evidence for clinical medication safety by the investigation of the risk factors of linezolid-related thrombocytopenia in cancer patients in the department of hepatobiliary surgery. Methods Patients who received linezolid for anti-infective treatment from January 2017 to December 2021 were selected. The patients were divided into thrombocytopenia group and non-thrombocytopenia group according to whether thrombocytopenia occurred or not after administration of linezolid. The general data and laboratory indicators of the two groups were compared, and the risk factors of linezolid-related thrombocytopenia were screened by multivariate logistic regression analysis. Results A total of 104 patients were included in the study, including 84 patients who underwent surgery and 20 patients who did not. The incidence of linezolid-related thrombocytopenia was 24.0%. There were significant differences in gender, age, duration of linezolid use, platelet count, white blood cell count, alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin, creatinine, estimated glomerular filtration rate between the two groups (P<0.05); logistic regression analysis suggested that age ≥60 years (OR=7.093; P=0.017), duration of linezolid use ≥12 days (OR=4.399; P=0.035), baseline platelet count ≤200×109/L (OR=8.470; P=0.004), baseline AST≥50 U/L (OR=15.465; P<0.001), and baseline white blood cell count ≥11×109/L (OR=11.436; P=0.001) were the risk factors for linezolid-related thrombocytopenia in cancer patients. Conclusion During the treatment of linezolid in cancer patients, attention should be paid to the adverse reactions of thrombocytopenia in the patients, especially those with old age, long-term treatment, low baseline platelets, poor baseline liver function, and high baseline white blood cell counts.
		                        		
		                        		
		                        		
		                        	
5.LncRNA DACH1 protects against pulmonary fibrosis by binding to SRSF1 to suppress CTNNB1 accumulation.
Jian SUN ; Tongzhu JIN ; Zhihui NIU ; Jiayu GUO ; Yingying GUO ; Ruoxuan YANG ; Qianqian WANG ; Huiying GAO ; Yuhan ZHANG ; Tianyu LI ; Wenxin HE ; Zhixin LI ; Wenchao MA ; Wei SU ; Liangliang LI ; Xingxing FAN ; Hongli SHAN ; Haihai LIANG
Acta Pharmaceutica Sinica B 2022;12(9):3602-3617
		                        		
		                        			
		                        			Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.
		                        		
		                        		
		                        		
		                        	
6.Common problems and solutions in hospital point-of-care testing quality management
Wei XU ; Hongli SHAN ; Ruiying SUN ; Linlin QU ; Hanxin YAO ; Feng WEI ; Xue WANG ; Hongshi CAO ; Yue CONG ; Haifeng WANG
Chinese Journal of Laboratory Medicine 2021;44(9):781-785
		                        		
		                        			
		                        			The rapid development of point-of-care testing (POCT) in clinical laboratories has brought challenges to the unified management in the hospital. There are many problems, such as how to ensure the ability and qualification of POCT operators, how to improve the quality management awareness of human, machines, materials, methods and environment in the process of POCT in clinical laboratories, how to help the clinical laboratories in the hospital to carry out POCT comparison, and how to strengthen the information construction of POCT in the hospital. Thus, this article reviews the practice and experience of POCT management in our hospital on POCT quality assurance and the problems existing in POCT in clinical departments, proposes suggestions and solutions to strengthen the unified management of POCT in clinical laboratories and establish POCT quality management documents and to improve quality awareness. We hope to provide references for hospital administrators, medical departments, nursing departments, quality control departments and other functional departments on the quality management of POCT in the hospital, and find helpful answers to the puzzles of clinical laboratory in POCT, so as to make joint efforts to standardize the quality management of POCT in the hospital to ensure the accuracy of testing results.
		                        		
		                        		
		                        		
		                        	
7.Periodic revalidation of autoverification for blood analysis and its suitability evaluation of application
Yingtong LI ; Xuejun WANG ; Wei XU ; Linlin QU ; Xianqiu CHEN ; Lijing WEI ; Ying WANG ; Hongli SHAN ; Zongxing YANG ; Yue CAI ; Xiaoquan YANG ; Wenrui SUN ; Dan LI ; Yue ZHANG ; Xi WANG ; Jin LIANG ; Jing HUANG ; Jiancheng XU ; Haiyan WANG ; Fang LIU ; Weining JIANG ; Chengming SHANG
Chinese Journal of Laboratory Medicine 2020;43(10):1021-1031
		                        		
		                        			
		                        			Objective:To conduct periodic revalidation of the 15 items and 43 terms autoverification rules of blood analysis after 1 year of application, analyze the application suitability and make the rules improved.Methods:Track the results of 528 010 blood analysis samples of our hospital from August 1, 2019 to January 31, 2020, and analyze the pass rate and interception rate of autoverification; 600 specimens in total were selected randomly for microscope examination, including 300 specimens which touched autoverification rules (1 012 items of autoverification rules) and were intercepted by autoverification and 300 specimens which untouched autoverification rules and were released by autoverification. The abnormal characteristics and unacceptable Delta check of the specimens also need to be concerned at the same time.The false negative rate and false positive rate, true negative rate, true positive rate and pass correct rate of autoverification were verified and compared with the rate of the second phase verification when the autoverification rule was established. The false negative rate, false positive rate, true negative rate and true positive rate of the Delta check rule which 54 716 specimens touched were calculated and compared with the second phase verification rate when the autoverification rule was established.The results of microscopic examination were used as the gold standard for the calculation of the rates, and P<0.05 was considered as a significant difference. The false positive and true positive of 1 012 autoverification rules were analyzed item by item.The false positive and true positive of 108 specimens which touched blast cell autoverification rule were analyzed terms by terms. The mean TAT and median TAT of 528 010 specimens and 193 750 outpatient specimens were calculated respectively, and the report percentages of 528 010 samples that TAT<30, 30-60 and>60 min were calculated respectively. Analyze and evaluate the application suitability of autoverification rules to juge whether they meet the needs of doctors and laboratory. The design process and the rules and application process of autoverification were optimized and improved.Results:The autoverification pass rate was 63.06% (332 971/528 010), the interception rate was 36.94% (195 039/528 010). The false negative rate was 1.00% (1/600), the false positive rate was 12.67% (76/600), the true negative rate was 49% (294/600), the true positive rate was 37.33% (224/600), and the correct rate was 98% (294/300). The pass rate, true negative rate, true positive rate and correct rate of the periodic reverification group were higher than the second phase verification group, the false negative rate and false positive rate were lower than that the second phase verification group. The false negative rate and true positive rate of the Delta check of periodic verification group were lower than that the second phase verification group, the false positive rate and true negative rate were higher than the second phase verification group, there were significant differences in the comparition results. The mean TAT of 528 010 specimens was25 min, and the median TAT was 22 min. The mean TAT of 193 750 outpatient specimens was 23 min, and the median TAT was 20 min. The report percentages of 528 010 samples that TAT<30 min, 30 min-60 min and>60 min were 83.30% (439 819/528 010), 8.00% (42 250/528 010) and 8.70% (45 941/528 010), respectively.Conclusion:The results of periodic revalidation of autoverification after 1 years application show that the 15 items and 43 terms autoverification rules of blood analysis could meet requirements about the accuracy and efficiency of the laboratory, and have a good suitability for application.
		                        		
		                        		
		                        		
		                        	
8.Correlation of type 2 diabetes and impaired glucose regulation with chronic kidney disease in middle-aged and elderly individuals.
Qiangmei WANG ; Jieyu ZHEN ; Conghui GUAN ; Nan ZHAO ; Jinjin LIU ; Hongli LI ; Songbo FU ; Xulei TANG ; Yanping HAN ; Shan SU ; Di ZHANG ; Lijuan LIU ; Donghu ZHEN
Journal of Southern Medical University 2020;40(10):1457-1464
		                        		
		                        			OBJECTIVE:
		                        			To explore the correlation of different glucose metabolism statues with chronic kidney disease (CKD) in middle-aged and elderly individuals in Lanzhou.
		                        		
		                        			METHODS:
		                        			Based on the baseline data of REACTION Study in Lanzhou area, we randomly sampled 10 038 residents aged 40-75 years in 3 communities in Lanzhou, who were classified into normal glucose tolerance (NGT), impaired glucose regulation (IGR) and diabetes groups. The estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) were used to assess the renal function and albuminuria, respectively. Binary logistic regression was performed to analyze the contribution of the risk factors to CKD. Polynominal regression was used to determine the trends of eGFR with the increment of ACR.
		                        		
		                        			RESULTS:
		                        			Among all the participants, the prevalences of albuminuria, CKD and renal insufficiency (RI) were 26.2%, 27.4% and 2.5%, respectively. The prevalence of albuminuria, CKD and RI were significantly higher in the diabetes group than in IGR and NGT groups (
		                        		
		                        			CONCLUSIONS
		                        			Diabetes mellitus is a significant risk factor for albuminuria and RI, while IGR is not. Screening for albuminuria and eGFR is highly recommended for individuals with diabetes, hypertension, and obesity, especially in women and the elderly population.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Albuminuria/epidemiology*
		                        			;
		                        		
		                        			Diabetes Mellitus, Type 2/epidemiology*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Glomerular Filtration Rate
		                        			;
		                        		
		                        			Glucose
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Prevalence
		                        			;
		                        		
		                        			Renal Insufficiency, Chronic/epidemiology*
		                        			;
		                        		
		                        			Risk Factors
		                        			
		                        		
		                        	
9.Association between balance and fails with spinal osteoporotic fractures in patients with rheumatoid arthritis
Hongli SUN ; Shengqian XU ; Wen LIU ; Shan QI ; Ying WU ; Jianhua XU
Chinese Journal of Rheumatology 2018;22(2):91-95
		                        		
		                        			
		                        			Objective To investigate the prevalence of balance deficiency and falls in patients with rheumatoid arthritis (RA),and to explore the effect of above factors on osteoporotic fracture (OPF).Methods A total of 386 patients with RA and 158 age,gender-matched normal subjects from Jan 2013 to Oct.2015 were recruited.Antero-posterior and lateral X-rays scanning of vertebral column (T5-L5) were conducted for each individual,and semi-quantity method was used as the standard for determining vertebral OPF.Falls in 296 RA were recorded in details.The balance ability of 263 cases were measured by Berg balance scale.Statistical analysis was performed with ttest and Chi-square text and logistic regression analysis.Results ① The prevalence of vertebral OPF in RA was 17.4%(67/386),which was 4.5 times the prevalence of the control group (6/158,3.8%) (x2=17.743,P<0.01).The occurrence rate of falls in RA was 20.3% during the last year (60/296).② Compared to RA without OPF,patients with OPF had lower Berg balance score (43±14 vs 33±15,t=4.150,P<0.01).Patients with falls also had lower Berg balance scale scorethan that in RA without falls (31± 16 vs 41±14,t=4.373,P<0.01).③ The prevalence of falls during the last year in RA with vertebral OPF was 39.2% (20/51),which was higher than that in RA without OPF (15.7%,22/140) (x2=12.036,P=0.01).The prevalence of falls during the last year in RA with Berg balance scale score <40 was 32.5%,which was higher than that in patients with Berg balance scale score≥40 (P<0.01).Incidence of Berg balance scale score <40 in patients with OPF (68.8%,33/48) was higher than that in group without OPF (29.7%,35/118) (x2=21.558,P<0.01).④ Logistic regression analysis found that age [OR=1.064,P=0.001,95%CI (1.025,1.103)] and falls [OR=2.735,P=0.021,95%CI(1.168,6.407)] were risk factors for OPF in RA patients,while Berg balance scale score [OR=0.957,P=0.016,95%CI (0.924,0.992)] was negatively correlated with spinal OPF in RA patients.Conclusion Falls and decreased balance capacity in RA are closely correlated with OPF in RA.
		                        		
		                        		
		                        		
		                        	
10.Identification and Validation of Circulating MicroRNA Signatures for Breast Cancer Early Detection Based on Large Scale Tissue-Derived Data.
Xiaokang YU ; Jinsheng LIANG ; Jiarui XU ; Xingsong LI ; Shan XING ; Huilan LI ; Wanli LIU ; Dongdong LIU ; Jianhua XU ; Lizhen HUANG ; Hongli DU
Journal of Breast Cancer 2018;21(4):363-370
		                        		
		                        			
		                        			PURPOSE: Breast cancer is the most commonly occurring cancer among women worldwide, and therefore, improved approaches for its early detection are urgently needed. As microRNAs (miRNAs) are increasingly recognized as critical regulators in tumorigenesis and possess excellent stability in plasma, this study focused on using miRNAs to develop a method for identifying noninvasive biomarkers. METHODS: To discover critical candidates, differential expression analysis was performed on tissue-originated miRNA profiles of 409 early breast cancer patients and 87 healthy controls from The Cancer Genome Atlas database. We selected candidates from the differentially expressed miRNAs and then evaluated every possible molecular signature formed by the candidates. The best signature was validated in independent serum samples from 113 early breast cancer patients and 47 healthy controls using reverse transcription quantitative real-time polymerase chain reaction. RESULTS: The miRNA candidates in our method were revealed to be associated with breast cancer according to previous studies and showed potential as useful biomarkers. When validated in independent serum samples, the area under curve of the final miRNA signature (miR-21-3p, miR-21-5p, and miR-99a-5p) was 0.895. Diagnostic sensitivity and specificity were 97.9% and 73.5%, respectively. CONCLUSION: The present study established a novel and effective method to identify biomarkers for early breast cancer. And the method, is also suitable for other cancer types. Furthermore, a combination of three miRNAs was identified as a prospective biomarker for breast cancer early detection.
		                        		
		                        		
		                        		
		                        			Area Under Curve
		                        			;
		                        		
		                        			Biomarkers
		                        			;
		                        		
		                        			Biomarkers, Tumor
		                        			;
		                        		
		                        			Breast Neoplasms*
		                        			;
		                        		
		                        			Breast*
		                        			;
		                        		
		                        			Carcinogenesis
		                        			;
		                        		
		                        			Data Mining
		                        			;
		                        		
		                        			Early Detection of Cancer
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Genome
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Methods
		                        			;
		                        		
		                        			MicroRNAs*
		                        			;
		                        		
		                        			Plasma
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Real-Time Polymerase Chain Reaction
		                        			;
		                        		
		                        			Reverse Transcription
		                        			;
		                        		
		                        			Sensitivity and Specificity
		                        			
		                        		
		                        	
            
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