Background Chrysotile is widely used in construction and industry. Research has shown that it is associated with lung fibrosis in occupational groups, but the involvement of microRNAs (miRNAs) in chrysotile-induced lung fibrosis has been less well studied, and the specific mechanism is still unclear. Objective Using next-generation sequencing technology to analyze the effects of chrysotile exposure on the miRNAs expression profiles of human lung epithelial cells (BEAS-2B cells), to explore the variations of differentially expressed miRNAs and related signaling pathways, and to identify potential targets and molecular mechanisms of chrysotile-induced lung fibrosis. Methods Chrysotile was analyzed with a laser particle size analyzer and an X-ray diffractometer for particle size and physical phase. BEAS-2B cells were exposed to chrysotile for designed time sessions (12, 24, and 48 h) and doses (0, 50, 100, and 200 μg·mL⁻¹). Cell viability was detected with a cell viability assay kit (CCK8); expression levels of Fibronectin, Collagen-Ⅰ, and α-smooth muscle actin (α-SMA) were detected by Western blot after exposure to 200 μg·mL⁻¹ chrysotile for 24 h. Sample correlation and changes in miRNAs expression profiles between the chrysotile-exposed and the control groups were analyzed by next-generation sequencing technology. The target genes of differentially expressed miRNAs were predicted and subjected to Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results The average particle size of the chrysotile dust sample used in this study was 3.58 μm, and the results of X-ray diffraction analysis confirmed the characteristic peaks of chrysotile. Compared with the control group, the chrysotile gradually inhibited the survival rate of BEAS-2B cells with increasing concentration and exposure time (P<0.01). The survival rates of the 50, 100, and 200 μg·mL⁻¹ chrysotile-exposed cells after 12 h exposure were 83.88%±1.86%, 78.07%±3.97%, and 71.95%±2.99%, respectively; the survival rates after 24 h exposure were 77.41%±1.58%, 69.57%±2.23%, and 62.79%±3.65%, respectively; the survival rates after 48 h exposure were 74.31%±4.93%, 65.84%±2.71%, and 52.74%±6.31%, respectively. The Fibronectin, Collagen-Ⅰ, and α-SMA protein expression levels were elevated in the 200 μg·mL⁻¹ chrysotile-exposed BEAS-2B cells (P <0.05). The results of principal component analysis showed that there were differences in the composition of the samples between the chrysotile exposure group and the control group, and a total of 163 differential miRNAs were screened, of which 79 were up-regulated and 84 were down-regulated. The results of GO analysis showed that the differential miRNAs were mainly associated with biological processes such as regulation of transcription by RNA polymerase II, regulation of DNA templated transcription, cellular differentiation, protein phosphorylation, lipid metabolism, and cell cycle, cellular components such as nucleus, cytomembrane, cytoskeleton, mitochondria, and endoplasmic reticulum, as well as molecular functions such as protein binding, metal ion binding, transferase activity, and DNA binding. The results of KEGG analysis revealed that the differential miRNAs were mainly enriched in cancer pathway, phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) pathway, Ras-associated protein 1 (Rap1) pathway, calcium pathway, cyclic guanosine monophosphate/ protein kinase G (cGMP-PKG) pathway, Hippo pathway, cyclic adenosine monophosphate (cAMP) pathway, and Ras pathway. Conclusion Chrysotile exposure could significantly inhibit BEAS-2B cell survival, elevate the expression of lung fibrosis-associated proteins, and induce differential miRNAs expression, affecting biological processes (such as lipid metabolism, protein phosphorylation, and cell cycle) and cell components (such as mitochondria and endoplasmic reticulum), and interfering with PI3K/AKT pathway, Hippo pathway, cAMP pathway, Rap1 pathway, and Ras pathway.

Aromatase inhibitors (AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for <60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network (NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e.g. T3-4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

Aromatase inhibitors ( AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for ＜60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network ( NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e. g. T3?4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

Aromatase inhibitors ( AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for ＜60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network ( NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e. g. T3?4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

Osteoblastic metastasis of breast cancer is relatively rare, but there are cases of misdiagnosis and mistreatment in clinical treatment. They can only be diagnosed by X ray or CT bone scan and must be identified from bone repair after effective treatment in patients with osteolytic or mixed bone metastases. Bone metastasis is often seen in the disease-free condition of breast cancer, and very few can occur in stage Ⅳ lesions prior to surgery. Based on the analysis of clinical phenomena, we questioned the evaluation criteria of the therapeutic effect on bone metastasis of breast cancer created by the World Health Organization and the MD Anderson Cancer Center and concluded the formation mechanism of bone metastasis. For patients with simple osteoblastic bone metastasis, we broke through the recommendations of the National Comprehensive Cancer Network guideline and advocated the concept of "noninterference" . Patients with positive hormone receptor can be treated with traditional endocrine therapy. Hormone receptor negative and/or human epidermal growth factor receptor 2 positive patients can be observed first, followed by chemotherapy and/or targeted therapy when there is osteolytic bone metastasis or visceral metastasis. Furthermore, bisphosphonates are not required since osteoblastic bone metastasis is generally not associated with the risk of bone related events. The active treatment of primary lesion should be taken into account in stage Ⅳ patient before operation.

Objective To explore the effect of prognosis of consolidation radiotherapy for patients after R0 resection of local recurrence after radical mastectomy. Methods Totally 110 breast cancer patients with local recurrence receiving R0 resection were admitted and treated in our hospital from January 1st, 2003 to November 30th, 2015 were retrospectively analyzed. Results The median local progression time of 74 patients receiving consolidation radiotherapy ( 67.3％) was remarkably better than that of those without radiotherapy(36 patients, 32.7％), and the difference was statistically significant (χ2 =8. 526, P<0.05). Meanwhile, there was no statistically significant difference (P>0.05) of distance disease-free survival and overall survival between the radiotherapy group and the non-radiotherapy group. Multifactor analysis indicated that pseudo-adjuvant endocrine therapy (χ2 =7.541,95％CI:27.1％ -80.4％, P <0.05), DDFS(≥2 years vs. <2 years,χ2 =4.068,95％CI:101.4％ -267％,P<0. 05) and pseudo-adjuvant radiotherapy(χ2 =14.126, 95％CI:21.7％ -80.4％, P <0. 05 ) were the independent risk factors affecting the OS of patients with local recurrence after R0 resection. Conclusions For the patients with local recurrence after R0 resection of local recurrence, it is recommended that consolidation radiotherapy should be done and the radiation field should include the same side of the chest wall and clavicle area lymphatic drainage area.

Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT. Effective treatment should be continued if the symptoms are relieved or osteogenesis is observed. Osteoblastic change in bone-window CT is a sign of improvement after treatment. Endocrine therapy is proper for ER-positive patients. The patients with initial osteoblastic metastasis should not be treated with salvage chemotherapy or anti-HER2 treatment, only if osteolytic metastasis or visceral metastasis is observed. Bishosphonates are just auxiliary drugs in bone metastasis, which should not be abused.

Objective To analysis the relationships between bone markers, bone-specific alkaline phosphatase (BAP) and cross-linked telopeptide of type Ⅰ collage (ICTP), and bone metastasis of breast cancer.Methods A total of 217 patients' serum were collected.The 217 cases were divided into two groups:109 cases with bone metastasis, 108 cases without bone metastasis. Serum BAP and ICTP was measured by ELISA. The relationships between factors of bone metastasis and serum levels of BAP, ICTP were analyzed.Results The levels of serum BAP and ICTP in bone metastases group were significantly higher than those in non-bone metastasis group[BAP:24.8 μg/L(7.60-213.70 μg/L) vs 21.2 μg/L(7.3～68.8 μg/L),ICTP:7.0μg/L(1.4～32.4 μg/L) vs 4.1 μg/L(0.0～15.8 μg/L) (P=0.003,P=0.000)].The level of serum BAP and ICTP in patients with multiple bone metastasis was significantly higher than that in patients with single bone metastasis[BAP:32.3 μg/L(9.A～213.7 μg/L) vs 18.1 μg/L(7.6～60.0 μg/L),ICTP:7.6 μg/L(1.4～32.4 μg/L) vs 4.9 μg/L(1.8～10.5 μg/L),(P=0.001,P=0.010)].The sensibility of BAP and ICTP was 45.0 ％ (49/109)and 46.8 ％ (51/109),respectively.The specificity of ICTP and BAP was 83.3 ％ (90/108)and 84.3 ％ (91/108),respectively.Joint detection of BAP and ICTP had improved sensibility in the diagnosis of bone metastasis in breast cancer patients. Conclusion Joint detection of serum bone biochemical markers ICTP and BAP have a little values for diagnosing bone metastasis in breast cancer patients.

Anti-angiogenesis drug has become an important method and a hot research field for treating cancers.Drugs such as bevacizumab,sunitinib,sorafenib,lapatinib,achieved good clinical effect in treating breast cancers,but they also brought a lot of problems that need to be concerned.

Metastatic breast cancer (MBC) is a heterogeneous disease that has a variety of different clinical scenarios. There are few recognized therapeutic standards for MBC. Combining recent international guidelines and consensus recommendations with our clinical practice experience, the article will introduce and comment many sides about the treatment for MBC patients.