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Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM. Improving the Ability of Diagnosis and Treatment of Difficult Diseases

To detect the relationship between CTGF in the bone marrow of MM patients and osteolytic lesion of myeloma, moreover, to investigate the clinical significance of CTGF in MM.Fifity-four MM patients treated in our hospital from March 2019 to April 2020 were enrolled, and 28 healthy volunteers were selected as the control group. The plasma in bone marrow of the patients was collected, and the ELISA was used to detect the level of CTGF in bone marrow plasma and the relationship between its and clinical characteristics were statistically analyzed.The CTGF level of MM patients was significantly higher than those in the healthy control group (P0.001); the CTGF level in male patients was higher than that in female patients (P=0.007); the CTGF level in MM patients with osteolytic lesions was significantly higher than patients without osteolytic lesions and controls (P=0.007, P=0.001). The CTGF level in MM patients was positively correlated with the number of bone lesions (P0.001, r=0.52). CTGF levels in patients with ≥3 bone lesions were significantly higher than those with3 bone lesions and without bone lesions (P=0.014, P=0.002). ROC curve result showed that CTGF expression level shows a significant diagnostic value for MM bone disease (P0.001).The abnormally high expression of CTGF level in MM patients is related to the degree of myelomas osteolytic lesions and can reflect the progress of MM.CTGF在多发性骨髓瘤患者中的表达及临床意义.研究多发性骨髓瘤（MM）患者骨髓中结缔组织生长因子（CTGF）水平及其与骨髓瘤溶骨性病变的关系，探讨CTGF在多发性骨髓瘤骨病中的临床意义.选取2019年3月-2020年4月在本院接受治疗的MM患者54例，同时选取28例健康志愿者作为对照组，收集受试者骨髓后分离骨髓上清，采用双抗体夹心酶标免疫分析法（ELISA）检测骨髓上清液中CTGF蛋白表达水平，分析其与临床相关指标之间的关系.MM患者的CTGF水平显著高于健康对照组 （P0.001）；男性患者CTGF水平明显高于女性患者（P=0.007）；有骨病组的MM患者CTGF水平明显高于无骨病组的患者和对照组（P=0.007，P=0.001）。 MM患者的CTGF水平与骨损害的病灶数呈正相关（r=0.52），≥3处骨损害患者骨髓CTGF水平显著高于3处骨损害患者和无骨损害患者 （P=0.014，P=0.002）。ROC曲线结果表明，CTGF表达水平对于MM骨病的诊断有显著的价值（P0.001）.MM患者CTGF水平异常高表达与骨髓瘤溶骨性病变的程度相关，能反映MM疾病的进展.

Objective: The aim of this study was to investigate possible mechanisms of LOX gene effects on invasion and metastasis of breast cancer cells by RNA interference. Methods: LOX-RNAi-LV was designed, synthesized, and then transfected into a breast cancer cell line (MDA-MB-231). Expression of LOX, MMP-2 and MMP-9 was determined by real-time PCR, and protein expression of LOX by Western blotting. Cell migration and invasiveness were assessed with Transwell chambers. A total of 111 cases of breast cancer tissues, cancer-adjacent normal breast tissues, and 20 cases of benign lesion tissues were assessed by immunohistochemistry. Results: Expression of LOX mRNA and protein was suppressed, and the expression of MMP-2 and MMP-9 was significantly lower in the RNAi group than the control group (P

To construct a breast cancer cell line MD-MB-231 stably overexpressing RSK4 gene and study its in vivo effects on tumor tumorigenesis.The MD-MB-231 cells were transfected with pcDNA3.1/Neo and pcDNA3.1/Neo-RSK4 by lipofectamin transfection respectively. The stable expression of RSK4 (MR11 and MR12) and control vector (MN10 and MN11) were inoculated into severe combined immunodeficiency (SCID) mice subcutis to establish a model of human breast cancer in SCID mice. The xenograft tumor growth, invasion and metastasis were observed after 6 - 10 weeks.The stable cell lines MR11, MR12 and MN10, MN11 were screened successfully. We constructed the human breast cancer transplanted model and dissected SCID mice. After 6 weeks, SCID mice subcutis of the MN10/MN11 group yielded 10/10 metastatic tumors versus 6/10 and 7/10 in the MR11/MR12 group respectively. MR11 and MR12 showed much smaller tumor sizes and significantly reduced tumor volume and weight versus MN10 and MN11 (P0.001). In the control group, visceral metastasis developed in 80% (8/10) of mice while in metastasis developed in 40% (4/10) of mice injected with RSK4-overexpressing MDA-MB-231 cells. Histological examination of hematoxylin and eosin-stained paraffin sections of lungs revealed numerous metastases in mice injected with vector control cells whereas RSK4-overexpressing cells showed markedly decreased metastatic lesions.Transplanted human breast cancer in SCID mice closely correlates with the disease course of clinical tumor patients. Overexpression of RSK4 can inhibit tumor growth of transplanted human breast cancer in SCID mice.

To study the expression and clinical significance of ribosomal S6 kinase-4 (RSK-4) in breast cancer and explore the role of RSK-4 in the genesis and development of breast cancer.The expression levels of RSK-4 mRNA and protein were detected in 56 cases of breast cancer and the normal breast tissues, as well as in 20 cases of breast benign lesions, by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry.The expression rates of RSK-4 mRNA in breast cancer, the normal breast tissues and breast benign lesions were 48.2%, 76.8% and 75.0%, respectively. The expression level of RSK-4 mRNA in breast cancer was significantly lower than those in normal breast tissues and breast benign lesions tissues (P0.05). The expression level of RSK-4 significantly correlated with tumor size and clinical stage (P0.05).The expression rate of RSK-4 protein was 39.3% in breast cancer tissues, which was significantly lower than that of normal breast tissues (71.4%) and breast benign lesions (75.0%, P0.01). The expression level of RSK-4 protein was lower in breast cancer with large tumor, high clinical stage and lymph node metastasis. In 56 cases of breast cancer samples, the consistency rate of RSK-4 mRNA and protein was 73.2%. A significant correlation was found between RSK-4 mRNA and protein (χ² = 10.254, P0.05).The down-regulation of RSK-4 expression in breast caner suggests that it is a breast cancer suppressor gene, and the lack or down-regulation of RSK-4 expression is involved in the genesis and progression of breast cancer.

To study the differential gene expression of adriamycin-resistance of breast cancer cell line MCF-7/ADR as compared with its parent cell MCF-7 and screen the related genes.The in vitro inhibitory rate of MCF-7/ADR and MCF-7 cell lines to ADM (adriamycin) was examined by MIT assay. Then a cDNA microarray representing 14,755 genes was used to analyze the expression profiles of these two breast cancer cell lines.The inhibitory rate of MCF-7/ ADR to ADM was lower than that of MCF-7(P0.05)and the drug resistance to ADR of MCF-7/ADR was stronger than that of MCF-7. There were 2374 differential expression genes in MCF-7/adr and MCF-7 cell lines, of which 1099 genes upregulated with 99 genes 10-fold upregulated and 1275 genes downregulated with 71 genes 10-fold downregulated. The important upregulated genes were Bcl-2, GSTP1, c-myc, MMP-1 and NNMT while those downregulated ones p53, p21, p27 and CYPIA1.Drug resistance of breast cancer is a complicated process involving the expression of many upregulated or downregulated genes. The application of gene chip in screening drug-resistant genes may be a new approach for selecting the optimal chemotherapeutic regimens. [Key words]

The major cause of death in breast cancer patients is distant metastasis. This study was to explore the expression and significance of small breast epithelial mucin (SBEM) mRNA, the specific marker of breast cancer, in peripheral blood of breast cancer patients.Expression of SBEM mRNA in peripheral blood samples from 67 breast cancer patients, 16 benign breast disease patients, and 20 healthy volunteers was detected by nested reverse transcription-polymerase chain reaction (nested RT-PCR).SBEM mRNA was not detected in healthy volunteers and benign breast disease patients. Positive rate of SBEM mRNA was 50.7% (34/67) in breast cancer patients. Positive rate of SBEM mRNA was 25.0% (2/8) in stage I patients, 45.8% (11/24) in stage II patients, 43.8% (7/16) in stage III patients, and 73.7% (14/19) in stage IV patients, respectively. Positive rate of SBEM mRNA was significantly higher in stage IV patients than in stages I, II, and III patients (P0.05). The expression of SBEM mRNA in peripheral blood was not correlated with patient's age, primary tumor size, pathologic type, and estrogen or progestin receptor status (P0.05).SBEM mRNA is specifically expressed in peripheral blood of breast cancer patients, and may be a marker of micrometastasis of breast cancer.