1.Clinical Dominant Disease of Traditional Chinese Medicine: Rheumatoid Arthritis
Jinping WANG ; Qingwen TAO ; Mei MO ; Zihan WANG ; Nan ZHANG ; Yuan XU ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):202-210
Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by erosive arthritis, with a high prevalence and disability rate. Although significant progress has been made in the treatment of RA in recent years, challenges such as suboptimal efficacy, drug resistance, severe side effects, and high costs of long-term treatment remain, especially for patients in the early stages of RA, as well as those with RA complications, comorbidities, and severe conditions. Hosted by the China-Japan Friendship Hospital and organized by the Youth Committee of the China Association of Chinese Medicine, the 27th session of the Clinical Dominant Disease Series (Rheumatoid Arthritis) Youth Salon invited nearly 20 experts and scholars from traditional Chinese medicine (TCM), western medicine, and interdisciplinary fields to actively discuss the clinical needs of modern medicine and the advantageous stages and aspects of TCM in RA. Experts at the salon agreed that TCM has unique advantages in the treatment of RA, especially during the early stage, periods of low to moderate disease activity, remission phase, and in addressing complications and comorbidities. TCM can achieve both prevention and treatment by regulating the immune system and restoring immune homeostasis. The integrated approach of traditional Chinese and western medicine demonstrates significant advantages in active RA, refractory cases, and stages with severe complications, by rapidly controlling disease progression, alleviating symptoms, enhancing the quality of life, and facilitating recovery. Given the frequent occurrence of multiple comorbidities in RA, TCM shows potential in regulating immunity, alleviating symptoms, and improving physical constitution, which provides new insights into the comprehensive treatment of RA with comorbidities. However, high-quality clinical studies on integrated traditional Chinese and western medicine in RA are still lacking. It is necessary to establish large-scale clinical cohorts and biological databases to provide a scientific basis for the development of precision-targeted therapies and clinical treatment protocols. In the future, individualized treatment strategies integrating traditional Chinese and western medicine are expected to become an important direction for improving the quality of life in RA patients.
2.Clinical Dominant Disease of Traditional Chinese Medicine: Rheumatoid Arthritis
Jinping WANG ; Qingwen TAO ; Mei MO ; Zihan WANG ; Nan ZHANG ; Yuan XU ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):202-210
Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by erosive arthritis, with a high prevalence and disability rate. Although significant progress has been made in the treatment of RA in recent years, challenges such as suboptimal efficacy, drug resistance, severe side effects, and high costs of long-term treatment remain, especially for patients in the early stages of RA, as well as those with RA complications, comorbidities, and severe conditions. Hosted by the China-Japan Friendship Hospital and organized by the Youth Committee of the China Association of Chinese Medicine, the 27th session of the Clinical Dominant Disease Series (Rheumatoid Arthritis) Youth Salon invited nearly 20 experts and scholars from traditional Chinese medicine (TCM), western medicine, and interdisciplinary fields to actively discuss the clinical needs of modern medicine and the advantageous stages and aspects of TCM in RA. Experts at the salon agreed that TCM has unique advantages in the treatment of RA, especially during the early stage, periods of low to moderate disease activity, remission phase, and in addressing complications and comorbidities. TCM can achieve both prevention and treatment by regulating the immune system and restoring immune homeostasis. The integrated approach of traditional Chinese and western medicine demonstrates significant advantages in active RA, refractory cases, and stages with severe complications, by rapidly controlling disease progression, alleviating symptoms, enhancing the quality of life, and facilitating recovery. Given the frequent occurrence of multiple comorbidities in RA, TCM shows potential in regulating immunity, alleviating symptoms, and improving physical constitution, which provides new insights into the comprehensive treatment of RA with comorbidities. However, high-quality clinical studies on integrated traditional Chinese and western medicine in RA are still lacking. It is necessary to establish large-scale clinical cohorts and biological databases to provide a scientific basis for the development of precision-targeted therapies and clinical treatment protocols. In the future, individualized treatment strategies integrating traditional Chinese and western medicine are expected to become an important direction for improving the quality of life in RA patients.
3.Additional role of low-density lipoprotein cholesterol on the risk of osteoporosis in men with or without coronary heart disease: a real-world longitudinal study.
Jing ZENG ; Zi-Mo PAN ; Ting LI ; Ze-Yu CHEN ; Xiao-Yan CAI ; Mei-Liang GONG ; Xin-Li DENG ; Sheng-Shu WANG ; Nan LI ; Miao LIU ; Chun-Lin LI
Journal of Geriatric Cardiology 2025;22(2):219-228
BACKGROUND:
Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.
METHODS:
The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model.
RESULTS:
During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437).
CONCLUSIONS
Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.
4.Progress of transcatheter aortic valve replacement in 2023
Mo-Yang WANG ; Zheng ZHOU ; Guan-Nan NIU ; Yang CHEN ; De-Jing FENG ; Xiang-Ming HU ; Wen-Ce SHI ; Yong-Jian WU
Chinese Journal of Interventional Cardiology 2024;32(1):14-19
Transcatheter aortic valve replacement(TAVR)has become one of the effective methods for treating patients with aortic valve disease.With the continuous maturity of technology,innovation of instruments and increasing experience,the indications for TAVR has been expanded.Following international trends,the number of TAVR in China has steadily increased with each passing year.In 2023,the long-term follow-up results of TAVR in low-risk AS patients further confirm the long-term benefits of TAVR.The relevant research on TAVR for patients with aortic regurgitation and patients with bicuspid aortic stenosis provide evidence support for the expansion of TAVR indications.At the same time,the development of valve devices and new technological innovations are emerging in an endless stream,and the new concept of full life cycle management is increasingly being valued.Especially in China,the development of local devices is progressing rapidly,and multiple devices have entered the clinical research stage.The clinical manifestations and research results are worth pursuing.
5.The correlation between disease activity and bone metabolism in patients with systemic lupus erythematosus
Yuanyuan LI ; Jing WANG ; Hanchao LI ; Lingfei MO ; Nan HU ; Yanhua WANG ; Lan HE
Chinese Journal of Rheumatology 2024;28(2):113-117
Objective:To analyze the bone turnover markers in systemic lupus erythematosus (SLE) patients with different disease activity and the risk factors of osteoporosis.Methods:In this retrospective study, a total of 417 SLE inpatients were enrolled from the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi′an Jiaotong University, from March 2019 to June 2020. According to SLEDAI score, the patients were divided into 3 groups: 281 patients disease with inactive disease group; 99 patients with mild active disease group; and 37 patients with moderate/severe active disease. ANOVA test was used to compare the differences in serum bone turnover markers (PTH, NOST, VITDT, β-crossl, TP1NP, Ca and P) and bone density (Spine L 1~4 and left femur) among the three groups, and Tukey's method was used for the two groups comparison. Logistic regression analysis was used to investigate the risk factors of osteoporosis. Results:Serum VITDT, β-crossl and Ca levels were significantly different among the 3 groups ( F=11.66, P<0.001; F=7.22, P<0.001; F=29.38, P<0.001). Compared with patients in the inactive group, patients with both the mild disease group (VITDT: t=3.94, P<0.001; Ca: t=5.10, P<0.001) and the moderate/severe disease group (VITDT: t=3.33, P<0.001; Ca: t=7.19, P<0.001) had lower VITDT levels [(20.3±9.7) ng/ml vs. (15.9±9.3) ng/ml vs. (14.8±7.4) ng/ml] and serum Ca levels [(2.19±0.15)mmol/L vs. (2.09±0.21)mmol/L vs. (2.00±0.16)mmol/L]. Moreover, the moderate/severe disease group patients had much lower serum Ca levels ( t=2.36, P<0.05), compared with patients with the mild disease group. Compared with the patients with inactive group, both the mild activey group ( t=3.06, P<0.01) and the moderate/severe activie group ( t=2.99, P<0.01) patients had higher serum β-crossl levels [(419±316) pg/ml vs. (543±424) pg/ml vs. (586±343) pg/ml]. Compared with patients with the inactive disease group both patienes with the mild active group and the moderate/severe disease group patients had significantly decreased spine BMD ( t=2.75, P<0.01; t=2.71, P<0.01), Z-score ( t=5.65, P<0.001; t=4.70, P<0.001), T-score ( t=3.02, P<0.01; t=3.37, P<0.001), whereas, no difference was found between the mild disease group and moderate/severe disease group. Compared with the inactive group patients, both the mild active group and moderate/severe disease group patients had lower left femur BMD levels ( t=2.83, P<0.001; t=2.65, P<0.001) and T-score ( t=2.24, P<0.05; t=1.977, P<0.05) and no difference was found between the mild disease group and the moderate/severe disease group. Logistic regression analysis showed that age [ HR (95% CI)=1.080 (1.052, 1.109), P<0.001], BMI [ HR (95% CI)=0.801 (0.704, 0.911), P<0.001], SLEDAI score [ HR (95% CI)=1.047 (1.025, 1.076), P<0.05] and cumulative glucocorticoids dose [1.046 (1.006, 1.087), P<0.05] were associated with osteoporosis of SLE patients. Conclusion:Abnormal bone metabolism and decreased bone density are associated with SLE disease activity in SLE patients, especially in those with advanced age, low BMI and receiving high cumulative dose of glucocorticoids. Osteoporosis should be proactively prevented in the SLE patients.
6.Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program
Ming-Ying LU ; Chung-Feng HUANG ; Chao-Hung HUNG ; Chi‐Ming TAI ; Lein-Ray MO ; Hsing-Tao KUO ; Kuo-Chih TSENG ; Ching-Chu LO ; Ming-Jong BAIR ; Szu-Jen WANG ; Jee-Fu HUANG ; Ming-Lun YEH ; Chun-Ting CHEN ; Ming-Chang TSAI ; Chien-Wei HUANG ; Pei-Lun LEE ; Tzeng-Hue YANG ; Yi-Hsiang HUANG ; Lee-Won CHONG ; Chien-Lin CHEN ; Chi-Chieh YANG ; Sheng‐Shun YANG ; Pin-Nan CHENG ; Tsai-Yuan HSIEH ; Jui-Ting HU ; Wen-Chih WU ; Chien-Yu CHENG ; Guei-Ying CHEN ; Guo-Xiong ZHOU ; Wei-Lun TSAI ; Chien-Neng KAO ; Chih-Lang LIN ; Chia-Chi WANG ; Ta-Ya LIN ; Chih‐Lin LIN ; Wei-Wen SU ; Tzong-Hsi LEE ; Te-Sheng CHANG ; Chun-Jen LIU ; Chia-Yen DAI ; Jia-Horng KAO ; Han-Chieh LIN ; Wan-Long CHUANG ; Cheng-Yuan PENG ; Chun-Wei- TSAI ; Chi-Yi CHEN ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(1):64-79
Background/Aims:
Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy.
Methods:
We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment.
Results:
The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset.
Conclusions
Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.
7.Quality value transfer of substance benchmarks in Sanpian Decoction.
Xue-Chun LIU ; Yu-Jia MO ; Qing ZHANG ; Wen-Jun HU ; Ruo-Nan SHEN ; Yue-Ying ZHAO ; Ze-Kang ZHANG ; Chang-Hai WANG ; Xing-Yue HUANG ; Yang LU ; Jie BAI
China Journal of Chinese Materia Medica 2022;47(8):2099-2108
According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.
Benchmarking
;
Chromatography, High Pressure Liquid
;
Drugs, Chinese Herbal
;
Glycyrrhizic Acid/analysis*
;
Paeonia
;
Quality Control
;
Thiocyanates
8.Analysis of hepatitis B virus infection status in patients with systemic lupus erythematosus
Jingjing ZHANG ; Yue JIA ; Lingfei MO ; Yanhua WANG ; Jing LUO ; Nan HU ; Lan HE ; Jing WANG
Chinese Journal of Rheumatology 2022;26(3):175-178
Objective:To investigate the effect of systemic lupus erythematosus (SLE) on the status of hepatitis B virus (HBV) infection, and provide data for clarifying the relationship between autoimmunity and infection.Methods:SLE patients in the department of rheumatology and immunology of the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to December 2019 were screened. A retrospective case-control study was carried out. SLE patients with positive hepatitis B surface antigen (HBsAg) were gender and age matched with chronic hepatitis B (CHB) in a 1∶4 ratio. Chi-square test was used to compared the positive rates of hepatitis B e antigen (HBeAg) and Paired-Samples t test or Signed rank Wilcoxon test was used to compare the HBV DNA load and HBsAg titer. Results:The positive rate of HBsAg in SLE patients was lower than the prevalence rate of HBsAg in general population in the second Chinese National Hepatitis Seroepidemiological Survey in 2006 [2.2%(27/1 227) vs 7.2%], but the positive rate of HBcAb was not obviously different from that in general population in China [33.9%(416/1 227) vs 34.1%]. Compared with matched CHB patients, the positive rate of HBeAg [37.0%(10/27) vs 58.3%(63/108), χ2=3.94, P=0.047], the HBV DNA load [0(0, 3.7) lg U/ml vs 4.8(2.2, 3.7) lg U/ml, Z=-5.37, P<0.001] and HBsAg titer [(2.0±1.5) lg U/ml vs (3.3±1.1) lg U/ml, t=-4.26, P<0.001] in SLE patients were lower. Conclusion:The HBV infection status of SLE patients is different from that of patients with chronic hepatitis B and the HBV infection is more likely to be controlled.
9.Initial clinical experience of left bundle branch pacing after transcatheter aortic valve implantation.
Tian Jie FENG ; Guang Yuan SONG ; Jie ZHAO ; Yang CHEN ; Guan Nan NIU ; Zheng ZHOU ; Zhen Yan ZHAO ; Mo Yang WANG ; Yong Gang SUI ; Ke Ping CHEN ; Wei HUA ; Yong Jian WU
Chinese Journal of Cardiology 2022;50(2):142-149
Objective: To investigate the efficacy and safety of left bundle branch pacing(LBBP) in patients after transcatheter aortic valve implantation (TAVI). Methods: This is a retrospective study. A total of 35 patients underwent TAVI and received pacemaker implantation from January 2018 to December 2020 in Beijing Fuwai Hospital were enrolled. Patients were divided into LBBP group (n=12) and right ventricular apex pacing (RVAP) group (n=23) according to the pacing position. The success rate of operation in LBBP group was calculated, and the occurrence of complications were observed, and the parameters of pacemaker were measured on the 3rd day and 1, 3 and 6 months after operation. The N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiographic and ECG indexes were compared between the two groups on the 3rd day and 1, 3, and 6 months after pacemaker implantation. Result: A total of 35 patients were included, The age was (76.4±7.7) years, including 19 males (54.3%). The procedure time ((86.58±17.10)min vs. (68.74±9.18)min, P<0.001) and fluoroscopy duration ((20.08±4.44)min vs. (17.00±2.26)min, P<0.001) were significantly longer in LBBP group compared with RVAP group. The operation success rate of LBBP group was 11/12. There was no serious operation related complications such as pneumothorax, hemothorax, electrode dislocation, infection, and lower limb bleeding. The patients were followed up for 7.43 (5.21, 9.84) months. The programmed parameters of pacemaker were in the ideal range and stable during follow-up. At 3 and 6 months after operation, the left ventricular ejection fraction in LBBP group was higher than that in RVAP Group (at 3 months: (60.75±2.89)% vs. (57.35±3.33)%, P=0.004; at 6 months: (63.17±3.33)% vs. (56.17±3.97)%, P<0.001), NT-proBNP values was lower in LBBP group than that in RVAP Group (at 3 months: 822 (607, 1 150)ng/L vs. 1 052 (902, 1 536)ng/L, P=0.006; at 6 months: 440 (330,679)ng/L vs. 783 (588, 1 023)ng/L, P=0.001). At 1, 3 and 6 months after operation, the QRS duration was shorter in LBBP group than that in RVAP group (1 month: 99 (97, 107)ms vs. 126(124, 130)ms, P<0.001; 3 months: 98(96, 105)ms vs. 129(128, 133)ms, P<0.001; 6 months: 96(94, 104)ms vs. 130(128, 132)ms, P<0.001). Conclusions: For patients with permanent pacemaker indications after TAVI, LBBP is feasible, safe and reliable. It could improve the cardiac function in the short term, the long-term effect of LBBP needs to be further observed.
Aged
;
Aged, 80 and over
;
Bundle of His
;
Cardiac Pacing, Artificial/methods*
;
Electrocardiography/methods*
;
Fluoroscopy
;
Humans
;
Male
;
Retrospective Studies
;
Stroke Volume
;
Transcatheter Aortic Valve Replacement/adverse effects*
;
Treatment Outcome
;
Ventricular Function, Left
10.Efficacy and survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer.
Yang LIU ; Meng XIU ; Xiang WANG ; Qing LI ; Jia Yu WANG ; Ying FAN ; Qiao LI ; Shan Shan CHEN ; Rui Gang CAI ; Hong Nan MO ; Fei MA ; Yang LUO ; Bing He XU ; Pin ZHANG
Chinese Journal of Oncology 2022;44(2):178-184
Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Carboplatin/therapeutic use*
;
Humans
;
Neoadjuvant Therapy/adverse effects*
;
Paclitaxel/therapeutic use*
;
Treatment Outcome
;
Triple Negative Breast Neoplasms/pathology*

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