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Background Circulating tumor cells (CTCs) has been demonstrated as a promising liquid biopsy marker for breast cancer (BC). However, the intra-patient heterogeneity of CTCs remains a challenge to clinical application. We aim at profiling aggressive CTCs subpopulation in BC utilizing the distinctive metabolic reprogramming which is a hallmark of metastatic tumor cells. Methods Oncomine, TCGA and Kaplan–Meier plotter databases were utilized to analyze expression and survival relevance of the previously screened metastasis-promoting metabolic markers (PGK1/G6PD) in BC patients. CTCs detection and metabolic classification were performed through micro-filtration and multiple RNA in situ hybridization using CD45 and PGK1/G6PD probes. Blood samples were collected from 64 BC patients before treatment for CTCs analysis. Patient characteristics were recorded to evaluate clinical applications of CTCs metabolic subtypes, as well as morphological EMT subtypes classified by epithelial (EpCAM/CKs) and mesenchymal (Vimentin/Twist) markers. Results PGK1 and G6PD expressions were up-regulated in invasive BC tissues compared with normal mammary tissues. Increased tissue expressions of PGK1 or G6PD indicated shortened overall and relapse-free survival of BC patients ( P  < 0.001). Blood GM + CTCs (DAPI + CD45 − PGK1/G6PD + ) was detectable (range 0–54 cells/5 mL) in 61.8% of tCTCs > 0 patients. Increased GM + CTCs number and positive rate were correlated with tumor metastasis and progression ( P  < 0.05). The GM + CTCs ≥ 2/5 mL level presented superior AUC of ROC at 0.854 (95% CI 0.741–0.968) in the diagnosis of BC metastasis (sensitivity/specificity: 66.7%/91.3%), compared with that of tCTCs (0.779) and CTCs-EMT subtypes (E-CTCs 0.645, H-CTCs 0.727 and M-CTCs 0.697). Moreover, GM + CTCs + group had inferior survival with decreased 2 years-PFS proportion (18.5%) than GM + CTCs − group (87.9%; P  = 0.001). Conclusions This work establishes a PGK1/G6PD-based method for CTCs metabolic classification to identify the aggressive CTCs subpopulation. Metabolically active GM + CTCs subtype is suggested a favorable biomarker of distant metastasis and prognosis in BC patients.

Background F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). Methods This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m 2 ) and cyclophosphamide (600 mg/m 2 ) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. Results The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 − 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. Conclusions A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. Trial registration ClinicalTrials.gov: NCT04174599, on 22/11/2019.

Recently, the inflammatory cytokine IL-6 has been reported as a potent inducer of epithelial-mesenchymal transition (EMT) in breast cancer cells with an epithelial phenotype. Furthermore, EMT induces stem cell features in normal and transformed mammary cells. We explored whether IL-6-induced EMT promoted the generation of breast cancer stem-like cells (BrCSCs) in epithelial-like breast cancer cells, and whether the cytokines EGF and bFGF, analogous to IL-6, per se induced epithelial-mesenchymal transition, resulting in the enrichment of BrCSCs in mammosphere cultures. Herein, we provide evidence that IL-6 is capable of generating CD44+ cells with stem-like properties through induction of the EMT in the epithelial-like T47D breast cancer cells. We also show that mammosphere cultures of epithelial-like breast cancer cells, T47D, MCF7, ZR-75-1 and MDA-MB-453 cells, consistently generated stem-like cancer cells solely as a result of the EGF and bFGF cytokines in the mammosphere media mediating EMT. This finding demonstrated the link between the inflammatory cytokine IL-6 and BrCSCs and identified an important mechanism for the enrichment of BrCSCs in mammosphere cultures. Thus, EMT appears to be a critical mechanism for the induction of cancer cells with stem-like properties, and EMT of non-stem cancer cells could be a source of CSCs.

Objective The objective was to explore the expression and potential functions of long noncoding RNA (lncRNA) and mRNAs in human breast cancer (BC). Methods Differentially expressed lncRNAs and mRNAs were identified and annotated in BC tissues by using the Agilent human lncRNA assay (Agilent Technologies, Santa Clara, CA, USA) and RNA sequencing. After identification of lncRNAs and mRNAs through quantitative reverse transcription polymerase chain reaction, we conducted a series of functional experiments to confirm the effects of knockdown of one lncRNA, TCONS_00029809, on the progression of BC. Results We discovered 238 lncRNAs and 200 mRNAs that were differentially expressed in BC tissues and para-carcinoma tissue. We showed that differentially expressed mRNAs were related to biological adhesion and biological regulation and mainly enriched in cytokine-cytokine receptor interaction, metabolic pathways, and PI3K-Akt signaling pathway. We created a protein–protein interaction network to analyze the proteins enriched in these pathways. We demonstrated that silencing of TCONS_00029809 remarkably inhibited proliferation, invasion, and migration of BC cells, and accelerated their apoptosis. Conclusions We identified a large number of differentially expressed lncRNAs and mRNAs, which provide data useful in understanding BC carcinogenesis. The lncRNA TCONS_00029809 may be involved in the development of BC.

Background Several studies have demonstrated that cardiovascular risk factors play a role in the etiology of breast cancer. However, the combined effect of cardiovascular risk factors on the risk of breast cancer is still uncertain. Methods Data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort of middle-aged women, were used to investigate the association of individual and combined cardiovascular risk factors with breast cancer. Cox proportional hazards models were applied to calculate the hazard ratio (HR) and 95% confidence intervals (CI). Results A total of 7501 women were included. During a mean follow-up of 19.7 years, 576 women were diagnosed with breast cancer. White women and premenopausal status were independently associated with increased risk of breast cancer. Of the individual cardiovascular risk factors, only obesity was independently associated with an increased risk of breast cancer (HR 1.29, 95% CI 1.04–1.61). Compared with women without cardiovascular risk factors, women having three or greater, but not those with fewer than three cardiovascular risk factors, had a significantly higher risk of developing breast cancer (HR 1.27, 95% CI 1.06–1.53). Subgroup analyses indicated that women with three or greater cardiovascular risk factors had higher risk of breast cancer among postmenopausal Black women, but not among premenopausal Black and White women. Conclusions Combinations of cardiovascular risk factors are associated with increased risk of breast cancer in middle-aged women, especially in postmenopausal Black women. Joint interventions to modify cardiovascular risk factors could be used to prevent breast cancer in these higher-risk individuals.

ObjectiveTo provide an accurate assessment of the prevalence of breast fibroadenoma in a large population and to confirm the diagnostic accuracy of ultrasound for fibroadenoma.DesignThis was a cross-sectional survey.SettingThis research was conducted at Nanfang Hospital, Guangzhou, Guangdong, China.ParticipantsA total of 11 898 women aged 18–40 years who underwent breast screening between 1 January 2019 and 31 December 2019 were included in the fibroadenoma prevalence study. From 1 June 2019 to 31 December 2019, 342 breast lesions with pathology reports and preoperative ultrasound images were collected for diagnostic fibroadenoma testing (vs histological diagnostic testing).Primary outcome measuresPearson’s χ2 test was performed to compare the prevalence of different lesions between age groups, and descriptive statistics were used to report the clinical characteristics of fibroadenoma. For ultrasound diagnosis, fibroadenoma was defined as a well-circumscribed lesion with round or oval shape, consisting of a homogeneously hypoechoic or isoechoic solid mass, located parallel to the chest wall with a smooth margin and no posterior shadowing. Diagnostic test results for breast fibroadenoma were stratified by diagnostic type (histological vs ultrasound).ResultsOf the women aged 18–40 years, 27.6% (3285/11 898) had an ultrasound diagnosis offibroadenoma. Of these, the prevalence of fibroadenoma was stable across age groups (p=0.14) and did not differ between the left and right sides of the breast. Almost two-thirds of women presented with a single fibroadenoma, and most fibroadenomas did not exceed 1 cm in size. The sensitivity and specificity for fibroadenoma were 97.0% (95% CI for sensitivity: 93.7% to 98.8%) and 91.4% (95% CI for specificity: 85.4% to 95.5%) for ultrasonography, respectively.ConclusionsThe prevalence of fibroadenoma in South China is as high as 27.6%, and ultrasound could be used as a tool to diagnose fibroadenoma.

Background Sauchinone is extracted from the root of Saururus chinensis and exhibits potent antitumor effects in various human cancers. However, how sauchinone is involved in breast cancer has not been well studied. Methods Cells apoptosis, cell proliferation, and cycle distribution were evaluated. Xenograft tumor mouse model was constructed to investigate the roles of sauchinone. The relevant protein expression was detected by western blot. Results We found that sauchinone significantly reduced proliferation and survival, also induced apoptosis of MCF‐7 and Bcap‐37 cells in vitro. Sauchinone significantly increased miR‐148a‐3p expression, and human epidermal growth factor receptor (HER)‐2 targeted on miR‐148a‐3p. Sauchinone exposure downregulated HER‐2 expression whose overexpression partly eliminated the inhibitory effect of sauchinone. Further, sauchinone efficiently inhibited breast cancer progression through downregulating HER‐2 expression in vivo. Conclusion Our results indicate that sauchinone efficiently inhibits breast cancer progression through regulating miR‐148a‐3p/HER‐2 axis, suggesting that sauchinone could be an effective anticancer agent for breast cancer. Sauchinone efficiently inhibits breast cancer progression through regulating miR‐148a‐3p/HER‐2 axis.

The mineral dust emitted from Central Asia has a significant influence on the global climate system. However, the history and mechanisms of aeolian activity in Central Asia remain unclear, due to the lack of well-dated records of aeolian activity and the intense wind erosion in some of the dust source areas (e.g., deserts). Here, we present the records of aeolian activity from a sedimentary sequence in the southern Gurbantunggut Desert of China using grain size analysis and optically stimulated luminescence (OSL) dating, based on field sampling in 2019. Specifically, we used eight OSL dates to construct chronological frameworks and applied the end-member (EM) analysis for the grain size data to extract the information of aeolian activity in the southern Gurbantunggut Desert during the last 900 a. The results show that the grain size dataset can be subdivided into three EMs (EM1, EM2, and EM3). The primary modal sizes of these EMs (EM1, EM2, and EM3) are 126.00, 178.00, and 283.00 µm, respectively. EM1 represents a mixture of the suspension components and saltation dust, while EM2 and EM3 show saltation dust transported over a shorter distance via strengthened near-surface winds, which can be used to trace aeolian activity. Combined with the OSL chronology, our results demonstrate that during the last 900 a, more intensive and frequent aeolian activity occurred during 450–100 a BP (Before Present) (i.e., the Little Ice Age (LIA)), which was reflected by a higher proportion of the coarse-grained components (EM2+EM3). Aeolian activity decreased during 900–450 a BP (i.e., the Medieval Warm Period (MWP)) and 100 a BP—present (i.e., the Current Warm Period (CWP)). Intensified aeolian activity was associated with the strengthening of the Siberian High and cooling events at high northern latitudes. We propose that the Siberian High, under the influence of temperature changes at high northern latitudes, controlled the frequency and intensity of aeolian activity in Central Asia. Cooling at high northern latitudes would have significantly enhanced the Siberian High, causing its position to shift southward. Subsequently, the incursion of cold air masses from high northern latitudes resulted in stronger wind regimes and increased dust emissions from the southern Gurbantunggut Desert. It is possible that aeolian activity may be weakened in Central Asia under future global warming scenarios, but the impact of human activities on this region must also be considered.

Intraoperative radiotherapy differs from the more commonly used external beam radiation with respect to fractionation, radiation energy, dose rate, and target volume, which may influence the irradiated cells in a complex manner. However, experimental studies of intraoperative radiotherapy are limited. Intrabeam is a frequently used intraoperative radiotherapy device; we evaluated its effects on the proliferation, apoptosis, migration, and invasion of MCF-7 human breast cancer cells. We performed colony formation assays for cells irradiated with single radiation doses of 0 to 16 Gy. Other cells were irradiated with single radiation doses of 0 to 6 Gy and then continued to be cultured. We measured cell-cycle distributions and apoptosis rates 24 hours later, using flow cytometry, and performed wound-healing assays, Transwell tests, and terminal deoxynucleotidyl transferase–mediated 2′-deoxyuridine 5′-triphosphate nick-end labeling staining 4 weeks later. Colony formation assays showed no positive colonies from cells irradiated with doses of ≥6 Gy. In flow cytometry, the experimental groups had higher late-apoptosis/necrosis rates (P < .01) and higher percentages of cells arrested in G1 phase (P < .01). Experimental groups also had much lower scratch-repair rates in the wound healing assay (P < .001) and higher apoptosis rates in the terminal deoxynucleotidyl transferase–mediated 2′-deoxyuridine 5′-triphosphate nick-end labeling assay (P < .05). In Transwell tests, the 4 Gy and 6 Gy groups had fewer invading cells than the control group (P < .05). Single-dose irradiation of 6 Gy with the Intrabeam device can effectively inhibit proliferation, migration, and invasiveness and promote apoptosis in MCF-7 cells with long-lasting effects.

This study took Nanchang as a research object and established an urban carbon metabolism process model based on carbon flow and an urban carbon metabolism analogy model based on Kleiber's law. The ecological relationship between land types and their changes caused by carbon flow in the process of land use change was studied by applying the ecological network analysis (ENA), and whether the relationship between urban carbon metabolism and the scale of construction land was consistent with the biometabolic law by using the panel data model. The results showed that the net carbon flow in Nanchang continued to show negative values from 2000 to 2020, and the mean value of the mutualism index (M) was less than 1, both factors indicating a negative impact of land use change. Exploitation and control relationships were the most major ecological relationships, dominated by urban land. The β values of the carbon metabolism models for rural settlements and other construction land were less than 1, implying an analogous relationship between carbon metabolism and biometabolism for both. The study provides a scientific foundation for national and local governments to formulate carbon emission reduction policies and plan low-carbon land use patterns.