1.Application of Thermal Tomography in Breast Cancer Screening
Kankan ZHAO ; Bo CHEN ; Wenliang LU ; Yao CHENG ; Hongmei ZHENG ; Xinhong WU ; Shengrong SUN ; Ziming HUANG
Cancer Research on Prevention and Treatment 2025;52(5):388-392
Objective To evaluate the effectiveness of thermal tomography in breast cancer (BC) screening. Methods We conducted a general population-based BC screening in three regions of Hubei Province (Xiantao, Hongan, and Yangxin Districts). Participants underwent a questionnaire-based interview for baseline data collection. They then received a physical examination, thermal tomography, and ultrasound from doctors and technicians. We compared the efficacies, including sensitivity, specificity, and false-positive rates, of ultrasound and thermal tomography in BC screening. Results A total of 59 712 eligible women were included in this screening program. The BI-RADS 1, 2, 3, 4, and 5 accordance rates between the two screening methods were
2.Value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices with significant portal hypertension in compensated hepatitis B cirrhosis
Cheng LIU ; Jiayi ZENG ; Mengbing FANG ; Zhiheng CHEN ; Bei GUI ; Fengming ZHAO ; Jingkai YUAN ; Chaozhen ZHANG ; Meijie SHI ; Yubao XIE ; Xiaoling CHI ; Huanming XIAO
Journal of Clinical Hepatology 2025;41(2):263-268
ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled, and according to the presence or absence of esophageal and gastric varices under gastroscopy, they were divided into esophageal and gastric varices group (GOV group) and non-esophageal and gastric varices group (NGOV group). Related data were collected, including age, sex, imaging findings, and laboratory markers. The chi-square test was used for comparison of categorical data between groups; the least significant difference t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of five scoring models, i.e., fibrosis-4 (FIB-4), LOK index, LPRI, aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase/alanine aminotransferase ratio (AAR). The binary logistic regression method was used to establish a combined model, and the area under the ROC curve (AUC) was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group, the GOV group had a significantly higher age (52.64±1.44 years vs 47.96±1.68 years, t=0.453, P<0.05) and significantly lower levels of alanine aminotransferase [42.00 (24.00 — 17.00) U/L vs 82.00 (46.00 — 271.00) U/L, Z=-3.065, P<0.05], aspartate aminotransferase [44.00 (32.00 — 96.00) U/L vs 62.00 (42.50 — 154.50) U/L,Z=-2.351, P<0.05], and platelet count [100.00 (69.00 — 120.00)×109/L vs 119.00 (108.50 — 140.50)×109/L, Z=-3.667, P<0.05]. The ROC curve analysis showed that FIB-4, LOK index, LPRI, and AAR used alone had an accuracy of 0.667, 0.681, 0.730, and 0.639, respectively, in the diagnosis of esophageal and gastric varices (all P<0.05), and the positive diagnostic rates of GOV were 69.97%, 65.28%, 67.33%, and 58.86%, respectively, with no significant differences in AUC values (all P>0.05), while APRI used alone had no diagnostic value (P>0.05). A combined model (LAF) was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%, with a significantly higher AUC than FIB-4, LOK index, LPRI, and AAR used alone (Z=-2.773,-2.479,-2.206, and-2.672, all P<0.05). ConclusionFIB-4, LOK index, LPRI, and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy, which provides a certain reference for clinical promotion and application.
3.Two new coumarin compounds from Angelica biserrata
Jia-cheng WU ; Han-tao ZHAO ; Feng-die YAN ; Qian-feng CHEN
Acta Pharmaceutica Sinica 2025;60(1):201-204
Two new coumarin glycosides were isolated and purified from the dichloromethane fraction of
4.Production of GTKO pigs and kidney xenotransplantation from pigs to rhesus macaques
Yan WANG ; Yue CHANG ; Chang YANG ; Taiyun WEI ; Xiaoying HUO ; Bowei CHEN ; Jiaoxiang WANG ; Heng ZHAO ; Jianxiong GUO ; Hongfang ZHAO ; Xiong ZHANG ; Feiyan ZHU ; Wenmin CHENG ; Hongye ZHAO ; Kaixiang XU ; Ameen Jamal MUHAMMAD ; Zhendi WANG ; Hongjiang WEI
Organ Transplantation 2025;16(4):526-537
Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68+ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.
5.Improvement effect and mechanism of Shengmai powder on heart failure mice with qi-yin deficiency
Lanfang KANG ; Jian LI ; Yating ZHAO ; Yingchun CHEN ; Guiyin CHEN ; Xiaobo NIE ; Jiao LIU ; Jie CHENG
China Pharmacy 2025;36(17):2127-2133
OBJECTIVE To study the improvement effect and mechanism of Shengmai powder on heart failure (HF) mice with qi-yin deficiency. METHODS The mice were randomly divided into blank group (water), model group (water), Shengmai powder low-, medium-, and high-dose groups [2.61, 5.22 and 10.44 g/kg (based on crude drug dosage)] and positive control group (metoprolol, 30 mg/kg), with 10 mice in each group. Except for the blank group, all other groups were subcutaneously injected with D-galactose, and a qi-yin deficiency HF mice model was established by continuous food restriction and weight-bearing swimming. At the same time of modeling, the corresponding medicine/water was gavaged once a day for five weeks. The general state of mice was recorded and the traditional Chinese medicine (TCM) syndrome score was evaluated. Behavioral experiments were conducted to investigate the total distance of open field action, the percentage of immobility time, and the swimming exhaustion time of mice. The contents of aspartate transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) in the serum of mice were detected; cardiac function indexes [heart rate, left ventricular ejection fraction (LVEF), left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular mass index and whole heart mass index] were all detected; the histopathological morphology of mice myocardium was observed; the level of cardiomyocyte apoptosis in mice was detected; mRNA expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), and Cleaved-caspase-3 in myocardial tissue of mice were detected; the phosphorylation levels of sarcoplasmic reticulum calcium regulatory related proteins [ryanodine receptor 2 (RyR2) and phospholamban (PLB)] in myocardial tissue of mice were detected. RESULTS Compared with the blank group, the body weight, total distance of open field action, swimming exhaustion time, LVEF, LVEDD, Bcl-2 mRNA expression level in myocardial tissue and PLB protein phosphorylation level in the model group were significantly reduced/shortened (P<0.05); TCM syndrome score, the percentage of immobility time, heart rate, LVESD, left ventricular mass index, whole heart mass index, cardiomyocyte apoptosis rate, the contents of CK, LDH and AST in serum, mRNA expression levels of Cleaved-caspase-3 and Bax and the phosphorylation level of RyR2 protein in myocardial tissue were significantly increased (P<0.05); there were inflammatory cell infiltration, disordered cell arrangement and obvious myocardial interstitial fibrosis in myocardial tissue. After the intervention of Shengmai powder, most of the above quantitative indexes in mice were significantly reversed (P<0.05), the inflammatory cell infiltration in myocardial tissue was reduced, and the degree of fibrosis was significantly reduced. CONCLUSIONS Shengmai powder can improve cardiac function, reduce the level of cardiomyocyte apoptosis and myocardial fibrosis in HF mice with qi-yin deficiency. Its mechanism may be related to the regulation of the expression of sarcoplasmic reticulum calcium regulation related proteins.
6.Tenecteplase versus alteplase in treatment of acute ST-segment elevation myocardial infarction: A randomized non-inferiority trial
Xingshan ZHAO ; Yidan ZHU ; Zheng ZHANG ; Guizhou TAO ; Haiyan XU ; Guanchang CHENG ; Wen GAO ; Liping MA ; Liping QI ; Xiaoyan YAN ; Haibo WANG ; Qingde XIA ; Yuwang YANG ; Wanke LI ; Juwen RONG ; Limei WANG ; Yutian DING ; Qiang GUO ; Wanjun DANG ; Chen YAO ; Qin YANG ; Runlin GAO ; Yangfeng WU ; Shubin QIAO
Chinese Medical Journal 2024;137(3):312-319
Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).
7.Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study
Changyang XING ; Xiujing XIE ; Yu WU ; Lei XU ; Xiangping GUAN ; Fan LI ; Xiaojun ZHAN ; Hengli YANG ; Jinsong LI ; Qi ZHOU ; Yuming MU ; Qing ZHOU ; Yunchuan DING ; Yingli WANG ; Xiangzhu WANG ; Yu ZHENG ; Xiaofeng SUN ; Hua LI ; Chaoxue ZHANG ; Cheng ZHAO ; Shaodong QIU ; Guozhen YAN ; Hong YANG ; Yinjuan MAO ; Weiwei ZHAN ; Chunyan MA ; Ying GU ; Wu CHEN ; Mingxing XIE ; Tianan JIANG ; Lijun YUAN
Chinese Medical Journal 2024;137(15):1802-1810
Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.
8.Exploring mechanism of Banxia Baizhu Tianma Decoction in intervening methamphetamine addiction from PI3K-Akt pathway and cell verification based on network pharmacology and cell verification
Han-Cheng LI ; Zhao JIANG ; Yang-Kai WU ; Jie-Yu LI ; Yi-Ling CHEN ; Ming ZENG ; Zhi-Xian MO
Chinese Pharmacological Bulletin 2024;40(10):1971-1978
Aim To investigate the mechanism of Banxia Baizhu Tianma Decoction(BBTD)in interfer-ing methamphetamine(MA)addiction using network pharmacology.Methods The mechanism of BBTD intervention in MA addiction was analyzed using net-work pharmacology,and MA-dependent SH-SY5Y cell model was further constructed to observe the effects of BBTD on cell model and PI3K-Akt pathway.Results A total of 88 active ingredients and 583 potential tar-gets of BBTD were screened.KEGG analysis showed that BBTD might intervene in MA addiction through PI3K-Akt,cAMP and other pathways.The molecular docking results showed that key active ingredients ex-hibited strong binding ability with core targets of PI3K-Akt pathway.In vitro experiments showed that MA-de-pendent model cells had shorter synapses,tended to be elliptical in morphology,had blurred cell boundaries,showed typical cell damage morphology,and had high intracellular expression of cAMP(P<0.01)and low expression of 5-HT(P<0.05).BBTD intervention could counteract the above morphology,cAMP,and 5-HT changes,suggesting that it had therapeutic effects on MA-dependent model cells.Western blot showed that MA modeling elevated the p-PI3K/PI3K(P<0.05)and p-Akt/Akt(P<0.01);BBTD inter-vention decreased their relative expression.Conclu-sions Gastrodin and other active ingredients in BBTD have therapeutic effects on MA addiction,and the mechanism may be related to regulation of PI3K-Akt pathway relevant targets.
9.Long-term therapeutic efficacy and prognosis analysis of complex high-risk coronary heart disease patients undergoing elective percutaneous coronary intervention with extracorporeal membrane oxygenation combined with intra-aortic balloon pump
Tian-Tong YU ; Shuai ZHAO ; Yan CHEN ; You-Hu CHEN ; Gen-Rui CHEN ; Huan WANG ; Bo-Hui ZHANG ; Xi ZHANG ; Bo-Da ZHU ; Peng HAN ; Hao-Kao GAO ; Kun LIAN ; Cheng-Xiang LI
Chinese Journal of Interventional Cardiology 2024;32(9):501-508
Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1%vs.0.7%,P=0.030),left main disease(43.9%vs.27.0%,P=0.018),triple vessel disease(90.9%vs.75.5%,P=0.009),and RCA chronic total occlusion disease(60.6%vs.35.5%,P<0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9%vs.16.7%,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7%vs.9.2%,P=0.031).The rates of 1-month MACE(4.5%vs.2.6%,P=0.435)and 1-year MACE(7.6%vs.7.9%,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95%CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95%CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.
10.Detection rate of 68Ga-PSMA-11 PET/CT and distribution characteristics of lesions in patients with biochemical recurrence after radical prostatectomy for prostate cancer
Qiaochu CHEN ; Yining WANG ; Xiang ZHOU ; Cheng WANG ; Haitao ZHAO ; Liangrong WAN ; Ruohua CHEN ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(9):528-532
Objective:To evaluate the detection rate and distribution characteristics of lesions in patients with biochemical recurrence (BCR) after radical prostatectomy for prostate cancer by 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT. Methods:From January 2020 to March 2024, 68Ga-PSMA-11 PET/CT examination results of 172 patients (age (69.4±6.5) years) with BCR after radical prostatectomy in Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The relationship between prostate specific antigen (PSA) levels and 68Ga-PSMA-11 PET/CT detection rate was explored. The location and quantity of lesions detected by 68Ga-PSMA-11 PET/CT were analyzed in BCR patients with clear location after local treatment, and data were analyzed by Fisher exact test. Results:The detection rate of 68Ga-PSMA-11 PET/CT in patients with BCR was 70.35%(121/172). The positive detection rate increased with the increase of PSA level, with detection rates of 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1.0 μg/L, 1.0 μg/L≤PSA<1.5 μg/L and PSA≥1.5 μg/L groups of 49.12%(28/57), 67.24%(39/58), 15/16 and 95.12%(39/41), respectively. After local treatment, 64 cases were diagnosed with 95 recurrent and metastatic lesions. Among them, 22(34.38%) had simple prostate bed recurrence, 23(35.94%) had simple lymph node metastasis, 7(10.94%) had simple bone metastasis, and 12(18.75%) had multi regional metastasis. The proportion of bone metastasis (18.75%, 12/64) was significantly lower than that of prostate bed recurrence and lymph node metastasis (both 50.00%(32/64); both P=0.002). Conclusions:68Ga-PSMA-11 PET/CT has a high detection rate in patients with BCR after radical prostatectomy, especially in patients with high PSA levels. The lesions are mainly distributed in the prostate bed and lymph nodes, while bone metastases are relatively rare, which provide a theoretical basis for the selection of more accurate treatment plans for BCR patients in the future.

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