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This study aimed to assess and compare the performance of different machine learning models in predicting selected pig growth traits and genomic estimated breeding values (GEBV) using automated machine learning, with the goal of optimizing whole-genome evaluation methods in pig breeding. The research employed genomic information, pedigree matrices, fixed effects, and phenotype data from 9968 pigs across multiple companies to derive four optimal machine learning models: deep learning (DL), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGB). Through 10-fold cross-validation, predictions were made for GEBV and phenotypes of pigs reaching weight milestones (100 kg and 115 kg) with adjustments for backfat and days to weight. The findings indicated that machine learning models exhibited higher accuracy in predicting GEBV compared to phenotypic traits. Notably, GBM demonstrated superior GEBV prediction accuracy, with values of 0.683, 0.710, 0.866, and 0.871 for B100, B115, D100, and D115, respectively, slightly outperforming other methods. In phenotype prediction, GBM emerged as the best-performing model for pigs with B100, B115, D100, and D115 traits, achieving prediction accuracies of 0.547, followed by DL at 0.547, and then XGB with accuracies of 0.672 and 0.670. In terms of model training time, RF required the most time, while GBM and DL fell in between, and XGB demonstrated the shortest training time. In summary, machine learning models obtained through automated techniques exhibited higher GEBV prediction accuracy compared to phenotypic traits. GBM emerged as the overall top performer in terms of prediction accuracy and training time efficiency, while XGB demonstrated the ability to train accurate prediction models within a short timeframe. RF, on the other hand, had longer training times and insufficient accuracy, rendering it unsuitable for predicting pig growth traits and GEBV.

This pilot study aimed to explore the effectiveness and safety of dexibuprofen suppository in the treatment of PDA in preterm infants. Preterm infants with gestational age <34 weeks and color Doppler echocardiographic evidence of hemodynamically significant PDA (hs PDA) with systemic hypoperfusion was intended to be included into this study since January 2020. As of January 1, 2021, this trial had recruited 87 preterm infants who met the inclusion criteria. Neonates were admitted into hospital within 1 hour after birth and were randomly assigned into two groups. Group one included 44 preterm newborns administered with oral ibuprofen. Group two included 43 preterm newborns administered with dexibuprofen suppository. This preliminary study showed that rectal dexibuprofen and oral ibuprofen were both effective for the closure of PDA, and the closure rate of dexibuprofen suppository was comparable to that of oral ibuprofen after the 1st and 2nd courses of treatment. In addition, rectal dexibuprofen did not increase the incidence of adverse outcomes, including bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and necrotising enterocolitis. This pilot study showed dexibuprofen suppository is as effective and safe as oral ibuprofen; yet, better designed, muticenter controlled studies are still needed.

Objective: Intraventricular hemorrhage (IVH) is a serious neurological complication in premature infants. This study aimed to investigate the white matter impairments and neurodevelopmental outcomes of severe IVH in extremely preterm infants with gestation age less than 28 weeks., Methods: We retrospectively evaluated the extremely preterm infants between 2017 and 2020. Neurodevelopmental outcomes were evaluated with the Bayley Scales of Infant and Toddler Development-III at 2 years of corrected age. Diffusional kurtosis imaging (DKI) was employed to evaluate the microstructural changes in white matter tracts. Mean kurtosis (MK) and fractional anisotropy (FA) values of DKI were measured in the brain regions including posterior limbs of the internal capsule (PLIC) and the corpus callosum at term equivalent age., Results: Of 32 extremely preterm infants with severe IVH during the follow-up period, 18 cases were identified as neurodevelopmental impairments. The delay rates of motor and language were 58.4% and 52.7%. The cases with neurodevelopmental impairments had lower MK and FA values in both bilateral PLIC and the corpus callosum. The analysis of multivariable regression models predicting motor and language outcomes at 2 years of corrected age, showed that the decreases of MK values in both PLIC and the corpus callosum at the term equivalent age contributed to a significantly increased risk of neurodevelopmental impairments (all p  < 0.05). During follow-up period, obvious loss of nerve fiber bundles was observed with DKI tractography., Conclusion: Motor and language abilities at age 2 years were associated with MK values of DKI at the term equivalent age in both PLIC and the corpus callosum of extremely preterm infants with severe IVH. The evaluation of white matter microstructural changes with MK values might provide feasible indicators of neurodevelopmental outcomes of extremely preterm infants with severe intraventricular hemorrhage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Guo, Zhao, Cai, Li, Xu, zhang, Zhang, Xie, Li, Chen, Cui and Lu.)

Objective: This study aims to identify the risk factors associated with short stature in children born small for gestational age (SGA) at full-term., Methods: This was a retrospective study. The subjects were full-term SGA infants who were followed up until the age of 2 years. The risk factors for short stature were identified with univariate and multivariate analyses., Results: Of 456 full-term SGA children enrolled in this study, 28 cases had short stature at 2 years of age. A significant decrease in placental perfusion was found in the short children group with intravoxel incoherent motion (IVIM) technology, which was an advanced bi-exponential diffusion-weighted imaging (DWI) model of magnetic resonance imaging (MRI) ( p = 0.012). Compared to non-short children born SGA at full-term, the short children group underwent an incomplete catch-up growth. Mothers who suffered from systemic lupus erythematosus were more likely to have a short child born SGA ( p = 0.023). The morbidity of giant placental chorioangioma was higher in the short children group. The pulsatility index (PI), resistivity index (RI), and systolic-diastolic (S/D) ratio of umbilical artery were higher in the short children group than in the non-short control group ( p = 0.042, 0.041, and 0.043). Multivariate analysis demonstrated that decrease of perfusion fraction ( f p ) in IVIM of placental MRI, chromosomal abnormalities, short parental height, and absence of catch-up growth were associated with a higher risk of short stature in children born SGA at full-term., Conclusion: Risk factors for short stature in full-term SGA children at 2 years of age included a decrease of perfusion fraction f p in IVIM of placental MRI, chromosomal abnormalities, and short parental height., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ling, Chen, Zhang, Pan, Gong, Zhang, Zhao, Chen, Cui and Lu.)

Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being ( p = 0.003), functional well-being ( p = 0.006), breast cancer subscale ( p = 0.038), and FACT-B Total scores ( p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Yu, Jia, Cui, Tian, Fan, Geng, Cao, Yang, Wang, Liang, Wang, Jiang, Duan, Wang, Li, Wang, Zhang, Jin, Tang, Li, Zhu, Zuo, Wang, Zhou, Xiang, Guo, Wang, Huang, Liu and Yu.)

Background: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction., Methods: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models., Results: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (p trend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (p interaction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (p interaction  = 0.0497). However, these interactions became insignificant after Bonferroni correction., Conclusion: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: To explore the preoperative evaluation of sentinel lymph node (SLN) biopsy using contrast-enhanced ultrasonography (CEUS) in early breast cancer patients and the involved disturbing factors. Methods: Eighty-three female early breast cancer patients who underwent concurrent surgery in the Affiliated Cancer Hospital of Zhengzhou University between January 2017 and May 2018 were enrolled. CEUS was used to seek SLN and determine lymph node metastasis after signature of preoperative informed consent. Rapid pathological examination was used to determine whether metastasis existed in SLN. The sensitivity, specificity, accuracy, the differences between CEUS and pathological results, and the involved disturbing factors were evaluated. Results: A total of 212 SLNs were detected by CEUS and SLN biopsy with an average of 2.6 SLNs detected per patient, including 39 SLNs with cancer metastasis (18.4%) and 173 SLNs without cancer metastasis (81.6%). Among the 83 patients, 29 patients were predicted SLN-positive preoperatively utilizing CEUS (including 21 cases with SLN pathological metastasis and 8 cases with non-metastasis), 54 patients were predicted SLN-negative (including 5 cases with SLN pathological metastasis and 49 cases with non-metastasis). The preoperative evaluation of SLN utilizing CEUS were performed with a sensitivity of 80.8% (21/26), specificity of 86.0% (49/57), positive predictive value of 72.4% (21/29), and negative predictive value of 90.7% (49/54), positive likelihood ratio of 5.75, negative likelihood ratio of 0.22, and the accuracy of 84.3% (70/83), respectively. The area under the ROC curve (AUC) was 0.834 (95% CI: 0.736-0.906). The primary tumor mean size of SLN-negative group predicted preoperatively utilizing CEUS was (1.78±0.14) cm, and that of the SLN positive group was (2.64±0.19) cm. The difference between the two groups was (0.86±0.24) cm with statistical significance ( P= 0.000 6). The SLN mean size of SLN-negative group (141 SLNs) was (1.41±0.05) cm and that of SLN-positive group (71 SLNs) was (1.69±0.07) cm. The difference between the two groups was (0.28±0.09) cm with statistical significance ( P= 0.002 8). Conclusions: Preoperative CEUS possesses the predictive value for SLN metastasis in early breast cancer. The predicted results may be influenced by the primary tumor size and the SLN size.

Background: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy., Methods: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety., Results: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153)., Conclusions: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

This study aimed to investigate risk factors associated with breast cancer among Han Chinese women in northern and eastern China. A matched case-control study involving 1489 patients with breast cancer and 1489 controls was conducted across 21 hospitals in 11 provinces in China, from April 2012 to April 2013. We developed a structured questionnaire to record information from face-to-face interviews with participants. Student's t-tests, Pearson's chi-square tests, and univariate and multivariate conditional logistic regression analyses were used to identify variables with significant differences between the case and control groups. Ten variables were identified (P < 0.05): location, economic status, waist-to-hip ratio, menopause, family history of breast cancer, present life satisfaction, sleep satisfaction, milk products, behavior prevention scores, and awareness of breast cancer. We identified a comprehensive range of factors related to breast cancer, among which several manageable factors may contribute to breast cancer prevention. Further prospective studies concerning psychological interventions, sleep regulation, health guidance, and physical exercise are required. A screening model for high-risk populations should be put on the agenda., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

Objective: To explore the Digital breast tomosynthesis technique (DBT) in breast cancer diagnosis accuracy. Methods: Choose 263 cases of patients with breast lesions, using DBT combined FFDM (Full field digital mammography) independent FFDM, evaluate the diagnostic accuracy of breast cancer. Results: The ROC curve area (AUC) of two kinds of breast cancer diagnosis methods (DBT combined FFDM and independent FFDM) were 0.954±0.014 and 0.907±0.019, with significant difference ( P =0.000 3). In premenopausal patients and breast density ACR3-4 cases, DBT combined FFDM diagnosis accuracy is higher than FFDM alone group, with significant difference ( P <0.05). Conclusion: DBT combined FFDM compared with independent FFDM, in a certain extent, improves the accuracy of the diagnosis of breast cancer.

Objective: This study was designed to investigate the prognostic implications of the intertumoral heterogeneity of molecular phenotype in multifocal and multicentric breast cancer (MMBC). Methods: The clinical and follow-up data of 146 patients with MMBC from Jan.2009 to Dec. 2009 treated in Tumor Hospital Affiliated to Zhengzhou University were retrospectively analyzed. We used Kaplan-Meier curves to compare the survivals of patients who had tumors with molecular phenotypic heterogeneity and patients who had multifocal homogeneous tumors in molecular phenotype, and the survivals of patients who had heterogeneous tumor type and grade and who had homogeneous tumor type and grade.The corresponding hazard ratio was calculated by Cox proportional-hazards regression. Results: Intertumoral heterogeneity in histological type and grade of multiple breast cancer was detected in 16 of 146 patients (11.0%) and in 10 of 146 patients (6.8%), respectively. Interfocal heterogeneous molecular phenotype of multiple breast cancer was detected in 24 of 146 patients (16.4%). There was no significant difference in 5-year disease-free survival in multifocal cancer patients who had heterogeneous histological type and grade and who had homogeneous type and grade tumors (75.0% vs. 77.3%, P =0.808). Multifocal cancers patients who had heterogeneous tumorsin molecular phenotype compared with those with homogeneous tumors in molecular phenotype had worse 5-year disease-specific survival (78.7% vs. 58.3%, P =0.037), and had a greater risk of recurrence ( HR =2.130, 95% CI =1.027-4.420; P =0.042). Phenotyping the additional cancer foci influenced the therapeutic decision in up to 16 patients(11.0%). Conclusions: Multifocal breast cancer patients who had heterogeneous tumors in molecular phenotype have a statistically significantly shorter disease-free survival. Phenotyping the additional cancer foci and managing with proper therapeutic decision may reduce the risk of recurrence or metastasis, and improve the outcomes of the patients.

The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.

Both pre-gestational and gestational diabetes have an adverse impact on heart development, but little is known about the influence on the early stage of heart tube formation. Using early gastrulating chick embryos, we investigated the influence of high glucose on the process of heart tube formation, specifically during the primary heart field phase. We demonstrated that high-glucose exposure resulted in 3 types of heart tube malformation: 1) ventricular hypertrophy, 2) ventricular hypertrophy with dextrocardia and 3) ventricular hypertrophy and dextrocardia with the fusion anomaly of a bilateral primary heart tube. Next, we found that these malformation phenotypes of heart tubes might mainly originate from the migratory anomaly of gastrulating precardiac mesoderm cells rather than cell proliferation in the developmental process of bilateral primary heart field primordia. The treatment of rapamycin (RAPA), an autophagy inducer, led to a similar heart tube malformation phenotype as high glucose. Additionally, high-glucose exposure promoted the expression of the key autophagy protein LC3B in early chick tissue. Atg7 is strongly expressed in the fusion site of bilateral primary heart tubes. All of these data imply that autophagy could be involved in the process of high-glucose-induced malformation of the heart tube.

Forkhead Box M1 (FOXM1) is an oncogenic transcription factor implicated in breast cancer progression and metastasis. However, the clinical significance of FOXM1 and its associated signaling genes in human breast cancer still needed to be clarified. In this study, we first analyzed the co-expression gene pattern of FOXM1 in three breast cancer gene expression microarray datasets from the Oncomine database. Cell division cycle associated 8 (CDCA8) gene was identified to correlate closely with FOXM1. In silico analysis further indicated that CDCA8 overexpressed in breast cancer tissues compared with the normal controls is significantly associated with the triple-negative phenotype. Experimentally, we performed a immunohistochemical study to detect the expression of CDCA8 in 112 breast cancer samples, and evaluated its clinicopathological and prognostic significance. We found that CDCA8 was frequently over-expressed in breast cancer tissues, and increased expression of CDCA8 was positively associated with FOXM1 expression, triple-negative phenotype and shorter overall survival. Moreover, we also found that combination of CDCA8 and FOXM1 showed a higher hazard ratio than the individual markers. Our results suggest that FOXM1-CDCA8 signature might be involved in breast cancer progression, and serves as a potential prognostic factor and a promising therapeutical target.

The treatment of a brain glioma remains one of the most difficult challenges in oncology. In the present study a delivery system was developed for targeted drug delivery across the blood-brain barrier (BBB) to the brain cancer cells. A cyclic arginine-glycine-aspartic acid (RGD) peptide and transferrin (TF) were utilized as targeting ligands. Cyclic RGD peptides are specific targeting ligands of cancer cells and TFs are ligands that specifically target the BBB and cancer cells. Liposome (LP) was used to conjugate the cyclic RGD and TFs to establish the brain glioma cascade delivery system (RGD/TF-LP). The LPs were prepared by the thin film hydration method and physicochemical characterization was conducted. In vitro cell uptake and three-dimensional tumor spheroid penetration studies demonstrated that the system could target endothelial and tumor cells, as well as penetrate the tumor cells to reach the core of the tumor spheroids. The results of the in vivo imaging further demonstrated that the RGD/TF-LP provided the highest brain distribution. As a result, the paclitaxel-loaded RGD/TF-LP presents the best antiproliferative activity against C6 cells and tumor spheroids. In conclusion, the RGD/TF-LP may precisely target brain glioma, which may be valuable for glioma imaging and therapy.

Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. The epidermal growth factor receptor (HER2) overexpressing breast cancers are designated as HER2-postive (HER2+) breast cancer and carry a particularly unfavorable prognosis. We present two cases of HER2-postive metastatic breast cancer (MBC) who are found to be a challenge to treat, especially due to the occurrence of brain metastasis. Trastuzumab-based therapy improves clinical outcomes, even if the patient has undergone multi-line treatment. These case reports also emphasize the importance of retesting HER2 status because it can be discordance in receptor status between primary and recurrent breast cancer.

This study aimed to investigate the clinical effects and safety review of self-expanding stent surgery in the treatment of extracranial carotid artery stenosis. Seventy-eight patients with carotid artery stenosis were applied with the self-expanding stent for endovascular interventional therapy. Eighty-one stents were implanted into 80 blood vessels of the 78 patients, in which protective umbrellas were used in 56 cases, and the success rate of stent implantation was 100%. The stenosis degree decreased from the preoperative (86.72 ± 9.5%) to the postoperative (13.43 ± 5.62%) stage, and the blood peak velocity of the stenosed vessels decreased from 189.58 ± 13.5 to 83.73 ± 5.61 cm/s. Transient blood pressure and heart rate decreases occurred in 21 cases, continuously low blood pressure and heart rate decreasing occurred in 29 cases, and acute occlusion of the ipsilateral middle cerebral artery occurred in 1 case, which was resolved through thrombolysis and thrombus breaking in time. Over-perfusion symptoms were observed in 13 cases, although without serious complications such as cerebral hemorrhage. The follow-up period continued for 6-32 months, and ultrasonography revealed that 77 cases had no stent-restenosis, while 1 case had restenosis. The application of self-expanding stents had good clinical effects, with fewer complications and higher safety for the treatment of extracranial carotid artery stenosis.

Background: Cancer stem cells (CSCs) are the cause of cancer recurrence because they are resistant to conventional therapy and contribute to cancer growth and metastasis. Endocrinotherapy is the most common breast cancer therapy and acquired tamoxifen (TAM) resistance is the main reason for endocrinotherapy failure during such therapy. Although acquired resistance to endocrine treatment has been extensively studied, the underlying mechanisms are unclear. We hypothesized that breast CSCs played an important role in TAM-induced resistance during breast cancer therapy. Therefore, we investigated the biological characteristics of TAM-resistant (TAM-R) breast cancer cells., Methods: Mammosphere formation and tumorigenicity of wild-type (WT) and TAM-R MCF7 cells were tested by a mammosphere assay and mouse tumor xenografts respectively. Stem-cell markers (SOX-2, OCT-4, and CD133) and epithelial-mesenchymal transition (EMT) markers were tested by quantitative real-time (qRT)-PCR. Morphological observation was performed to characterize EMT., Results: After induction of TAM resistance, TAM-R MCF7 cells exhibited increased proliferation in the presence of TAM compared to that of WT MCF7 cells (P < 0.05), indicating enhanced TAM resistance of TAM-R MCF7 cells compared to that of WT MCF7 cells. TAM-R MCF7 cells showed enhanced mammosphere formation and tumorigenicity in nude mice compared to that of WT MCF7 cells (P < 0.01), demonstrating the elevated CSC properties of TAM-R MCF7 cells. Consistently, qRT-PCR revealed that TAM-R MCF7 cells expressed increased mRNA levels of stem cell markers including SOX-2, OCT-4, and CD133, compared to those of WT MCF7 cells (P < 0.05). Morphologically, TAM-R MCF7 cells showed a fibroblastic phenotype, but WT MCF7 cells were epithelial-like. After induction of TAM resistance, qRT-PCR indicated that MCF7 cells expressed increased mRNA levels of Snail, vimentin, and N-cadherin and decreased levels of E-cadherin, which are considered as EMT characteristics (P < 0.05)., Conclusion: TAM-R MCF7 cells possess CSC characteristics and may be responsible for TAM resistance during breast cancer therapy.

Background: The incidence of brain metastases in patients with breast cancer is approximately 10% - 16%, and survival after diagnosis of brain metastases is usually short. This study was designed to evaluate the risk factors associated with brain metastases in advanced breast cancer patients, with a view to help predict patient groups with high risk of brain metastases., Methods: In total, 295 patients with advanced breast cancer were evaluated. All patients were pathologically confirmed and metastatic lesions were confirmed pathologically or by imaging. All patients were examined at least once every 6 months with head CT or MRI. Patients showing symptoms underwent immediate inspection, and brain metastatic lesions were confirmed by head CT and/or MRI., Results: At a median follow-up of 12 months from the occurrence of metastases, brain metastases had occurred in 49 patients (16.6%). In our univariate analysis, variables significantly related to increased risk of brain metastases were hormone receptor-negative tumors, epidermal growth factor receptor 2 (HER2)-positive tumors, and multiple distant metastases. Patients with dominant tumor sites in soft tissue, or defined as Luminal A subtype, tended to have a lower risk of brain metastases than patients with visceral metastases, Luminal B subtype, triple-negative subtype or HER2-enriched subtype tumors., Conclusions: Our results strongly suggest that factors such as Luminal B, triple-negative, and HER2-enriched subtypes are high risk factors for brain metastases. These data, therefore, provide pivotal clinical evidence towards a comprehensive understanding of the risk factors of brain metastases in advanced breast cancer patients.

Objective: To explore the effects and underlying mechanisms of high glucose on in vitro invasiveness of human breast cancer cell line MDA-MB-435., Methods: The invasiveness of MDA-MB-435 was determined by Matrigel-coated transwell chambers. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed to analyze the cellular expression of matrix metalloproteinase-9/matrix metalloproteinase-2/E-cadherin (MMP-9/MMP-2/E-cadherin) gene/protein., Results: The invasive breast cancer cell numbers of each group (Glu 5.5, 11 and 25 mmol/L) were 50 ± 5, 65 ± 6 and 77 ± 3 respectively. Cellular invasion was dramatically enhanced in the Glu 11 and 25 mmol/L group compared with the 5.5 mmol/L group. The MMP-9/MMP-2 protein expression increased significantly in the Glu 11 and 25 mmol/L groups compared with 5.5 mmol/L group while high glucose (Glu 11 and 25 mmol/L group) down-regulated significantly the E-cadherin mRNA/protein expression., Conclusion: High glucose can promote the in vitro invasiveness of human breast cancer cells through the altered expression of MMP-9/MMP-2/E-cadherin.

Large-scale profiling approaches have revealed global down-regulation of microRNAs (miRNAs) in several human cancer types including breast cancer. Altered expression of Dicer and Drosha, two key enzymes in the miRNA maturation, is believed to be one of the most important mechanisms. By using quantitative real-time RT-PCR (QT-PCR), we examined the expression of Dicer and Drosha in 49 pairs of matched human breast cancer tissues. Decreased expression was observed in 53.1% (Dicer), 51.9% (Drosha) and 75.5% (Dicer plus Drosha) breast cancer tissues. In conclusion, the decreased expression of Dicer and Drosha may play a role in down-regulation of miRNAs in breast cancer.

Background: Keratinocyte serum-free medium (K-SFM) is a defined medium used to support the growth of primary keratinocytes and embryonic stem cell. The aim of this research was to optimize enrichment of breast cancer stem cells (CSCs) using K-SFM., Methods: A K-SFM was used to enrich CSCs from two breast cancer cell lines and a primary culture of breast cancer. RPMI-1640 supplemented with 10% fetal calf serum (FCS) was used as a control. CSCs were identified with flow cytometry using CD44(+)/CD24(-) as molecular markers. The expression of a variety of CSC markers (Oct-4, ABCG2, Nanog, N-cadherin, and E-cadherin) was analyzed with real-time PCR., Results: Much higher percentage of CSCs was achieved with K-SFM: 17.3% for MCF-7 cells, 17.4% for SKBR-3, and 20.0% for primary breast cancer culture. Less than 1% CSC was achieved using RPMI-1640 supplemented with 10% FCS. In comparison to the CSCs obtained with RPMI-1640, CSCs in the K-SFM expressed higher levels of Oct-4, ABCG2, Nanog and N-cadherin, and lower level of E-cadherin., Conclusion: K-SFM is an optimal culture medium to maintain and to enrich breast CSCs.

Objective: To investigate the value of technetium-99m methoxyisobutylisonitrile ((99)Tc(m)-MIBI) imaging in predicting the efficacy of neoadjuvant chemotherapy (NCT) and prognosis in patients with operable breast cancer., Methods: Sixty five patients with breast cancer underwent (99)Tc(m)-MIBI scintimammography before NCT, and static planar images were taken at 10 min and 180 min after scintimammography. The clearance rate was calculated in each patient, correlation between the clearance rate and efficacy of NCT, and the disease free survival rate were analyzed., Results: The mean clearance rate of 65 patients was (17.4 ± 6.8)%. The efficacy of NCT was 86.2% (CR 4 cases, PR 52 cases, SD 8 cases, and PD 1 case), and the mean clearance rate of patients with good response or poor response of chemotherapy were (15.5 ± 5.0)% and (29.2 ± 3.2)%, respectively. There was a significant difference between the two groups. The average disease free survival rate in the group with low clearance rate was (75.8%, P = 0.046), significantly higher than that in the group with high clearance rate (53.1%)., Conclusion: Scintimammography of (99)Tc(m)-MIBI may be used to evaluate the efficacy and prognosis of NCT for patients with operable breast cancer.

Objective: To evaluate the relationship between the clearance rate of technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) in scintimammography and the efficacy of neoadjuvant chemotherapy (NCT) of patients with operable breast cancer., Methods: Seventy-eight patients with breast cancer underwent (99m)Tc-MIBI scintimammography at pre-NCT. And static planar images were taken at 10 min and 180 min post-scintimammography. The clearance rate was calculated in each patient. And the efficacy of NCT was evaluated after 2 cycles., Results: The clearance rates of patients with a poor or good efficacy of chemotherapy were 24.21% ± 6.38% (n = 14) and 14.13% ± 5.98% (n = 64) respectively. There was significant difference between two groups. And a significant correlation was observed between the efficacy of chemotherapy and the clearance rate of (99m)Tc-MIBI (r = -0.539, P < 0.001)., Conclusion: The scintimammography of (99m)Tc-MIBI may be employed to evaluate the efficacy of NCT.

Objective: To investigate the expressions of X-linked inhibitor of apoptosis protein (XIAP)-associated factor-1 (XAFI) and heat-shock transcription factor 1 (HSF1) and their relationship in human gastrointestinal cancers., Methods: Immunoblotting was used to analyze the expressions of HSF1 and XAF1 in gastric and colon cancer tissues and in gastrointestinal cancer cells. The gastrointestinal cancer cells were tranfected with a eukaryotic expression vector containing HSF1 gene fragment or subjected to RNA interference to induce up- or down-regulation of HSF1 expression, and the consequence changes in XAF1 expression in the cells was measured. XAF1 expression was also assayed in the cells after stress stimulation for HSF1 expression., Results: The expression of HSF1 was higher in gastrointestinal cancer tissues than in normal tissues. The expression of XAF1 and HSF1 was inversely correlated in the cancer cell lines, and stress stimuli of the cells up-regulated the expression of HSF1 but down-regulated XAF1 expression., Conclusion: HSF1 expression is increased in gastrointestinal cancer tissues to result in suppressed expression of XAF1, which may be one of the reasons for the low expression of XAF1 in association with the defect of the apoptosis mechanisms in the cancer cells

Objective: X-linked inhibitor of apoptosis protein (XIAP) To gastrointestinal (GI) investigate the expression of XAF1 and heat-shock transcription factors 1 èHSF1éand their relationship in human gastrointestinal cancers., Methods: Immunoblotting was used to analyze the expression of HSF1 and XAF1 in either gastric or colon cancer tissue and GI cancer cell line. Transient expression of the HSF1-containing vector in GI cell lines and RNA interference were used to up/down-regulae the expression of the HSF1, and the subsequent expression of XAF1 was measured., Results: The expression of HSF1 was higher in GI cancers than in normal tissues. The expression of XAF1 and HSF1 was negatively correlated in GI cancer cell lines. Stress stimuli up-regulated the expression of HSF1 while the alteration of XAF1 expression was negatively correlated with HSF1 expression., Conclusion: The high expression of HSF1 in GI cancers is associated with suppressed expression of XAF1, which can be one of the mechanisms for low-expression of XAF1 and insufficient apoptosis in GI cancers.

Objective: To evaluate the relationship between the clearance rate of technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) in scintimammography and multidrug-resistant proteins expression in breast cancer tissues., Methods: Seventy-six patients with breast cancer underwent (99m)Tc-MIBI scintimammography before treatment, and static planar images were taken at 10 min and 180 min after scintimammography. The clearance rate of (99m)Tc-MIBI was calculated in each patient. Immunohistochemical analysis was performed on pathological specimens of the 76 breast tumors to determine the expression of P-glycoprotein (P-gp), glutathione S-transferase Pi (GST-pi) and topoisomerase II (Topo II)., Results: The clearance rate was significantly higher in 36 patients with positive P-gp expression when compared with that in 40 patients with negative P-gp expression. There was no significant relationship between GST-pi, Topo II and the clearance rate of (99m)Tc-MIBI., Conclusion: The clearance rate of (99m)Tc-MIBI in breast imaging may be used to evaluate the P-gp level in breast cancers.

Background & Objective: Heparanase is a heparan sulfate proteoglycan cleaving enzyme. It helps to degrade extracellular matrix and basement membrane, promote angiogenesis, and accelerate tumor metastasis. This study was to investigate correlation of heparanase expression to angiogenesis and prognosis of breast cancer., Methods: Immunohistochemistry was used to detect heparanase and microvessel density (MVD) in 120 specimens of infiltrative ductal breast cancer, and 10 specimens of normal breast tissue. Correlation of heparanase expression to clinicopathologic factors and prognosis of breast cancer were analyzed using Chi-square test, t test, Kaplan-Meier method, and log-rank test., Results: Positive rate of heparanase in breast cancer was 65% (78/120), significantly higher than that in normal breast tissue (0, 0/10) (P< 0.05). MVD in breast cancer was 53.84+/-13.45, significantly higher than that in control group (33.32+/-8.55) (P< 0.01). Expression of heparanase positively correlated with tumor size, histological grade, lymph node metastasis, and clinical stage (P< 0.05) of breast cancer, and negatively correlated with 5-year survival rate (P< 0.05). MVD in heparanase positive group was much higher than that in heparanase negative group (P< 0.05), MVD positively correlated with heparanase expression (r=0.358,P< 0.01)., Conclusion: Heparanase may promote angiogenesis, and may closely correlate with prognosis of breast cancer.