ObjectiveTo analyze clinicopathological characteristics and treatment of male breast cancer (MBC) and the matched female breast cancer (FBC). To compare the survival difference between the 2 groups.To study the factors influencing the prognosis of MBC.Methods63 MBC patients treated in Tianjin Medical University Cancer Institute and Hospital from Jan.1995 to Dec.2008 were enrolled in this study.Each MBC patient in the database was matched with 2 FBC patients.The matching criteria were with similar age, diagnosis time, and TNM stage.Chi-square test and Fisher exact test were employed to compare the clinicopathologic characteristics of MBC and FBC.Kaplan-Meier method, Log-rank test, and Cox hazard regression model were employed respectively to make survival analysis, surival rate comparison and multivariate analysis.ResultsThe 10-year disease-free survival (DFS) rate was 53.9％ for men and 65.1％ for women (P =0.047).The 10-year overall survival (OS) rate was 61.9％ for men and 77％ for women (P =0.032).Univariate analysis showed TNM stage, surgical method and recurrence were factors influencing the prognosis of MBC patients. Multivariate analysis showed TNM stage was an independent factor influencing the prognosis of MBC patients.ConclusionsFBC patients had a better 10-year OS rate and DFS rate than MBC patients.TNM stage is an independent factor influencing the prognosis of MBC patients.

The aim of this project is to establish a fibroblast growth factor-21 (FGF-21) signaling pathway targeted cell model, for screening a class of FGF-21 receptor agonists as anti-diabetic candidates. FGF-21 requires beta klotho transmembrane proteins as co-receptor for the activation of tyrosine kinase FGF receptor (FGFR) signaling, thereby activating a series of intracellular signaling pathways and regulating gene transcription for glucose metabolism. Firstly a recombinant plasmid expressing co-receptor beta klotho and EGFP reporter genes was constructed. After introducing the recombinant plasmid into package cells, the cell culture supernatant was used to infect 3T3-L1 cells, which were then screened for stably expressing beta klotho gene. Administration of FGF-21 increased the expression of GLUT1 and stimulated GLUT1-mediated glucose uptake. This novel cell model can be conveniently used in high-throughput drug screening of FGF-21 or FGF-21 analogues.

Objective To evaluate the relationship between neoadjuvant chemotherapy (combination of taxanes and anthracyclines ) induced-neutropenia and the efficacy of neoadjuvant chemotherapy and long-term survival in operable breast cancer patients. Methods Two hundred and eleven patients received 4 cycles of neoadjuvant chemotherapy (combination of taxanes and anthracyclines).Clinicopathological characteristics were compared between patients with neoadjuvant chemotherapy-induced neutropenia and patients without neutropenia. The efficacy of neoadjuvant chemotheray and long-term survival rate were analyzed. Results Among 211 patients there were 51 (24. 2% ) cases suffering from neutropenia and 160 (75.8%) cases were of no-neutropenia. The response to chemotherapy in patients with neutropenia were more effective than in no- neutropenia ones ( P ＜ 0. 05 ). The 5-year disease-free survival (DFS) in patients with neutropenia was 82. 4%, while the 5-year disease-free survival ( DFS) with nonneutropenia was 60% ( P ＜ 0. 01 ). Additionally, the 5-year overall survival ( OS ) in patients with neutropenia was 90. 2% and in patients with non-neutropenia patients was 67. 5% ( P ＜ 0. 01 ).Conclusions Chemotherapy-induced neutropenia during neoadjuvant chemotherapy combination of taxanes and anthracyclines in patients with operable breast cancer has a better prognosis. The sensitivity of tumors given to chemotherapeutic drugs could be evaluated by chemotherapy-induced neutropenia.

Objective To investigate the association between the obstructive sleep apnea-hypopnea syndrome(OSAHS) in hypertension and insulin.Methods A total of 521 patients were divided into 4 groups according to apnea-hypopnea index and OSAHS degrees.The control group ( group Ⅰ ),mild OSAHS group ( group Ⅱ ),moderate OSAHS group ( group Ⅲ ) and severe OSAHS group ( group Ⅳ ) had 89 patients,194 patients,118 patients and 120 patients respectively.Results The BMI[( 30.4 ± 3.8 )kg/m2],apnea-hypopnea index ( AHI,3.8 ± 0.1 ),Fasting insulin (FIns)[(3.08 ± 0.26 ) mU/L]and insulin resistance ( 2.43 ± 0.27 ) of patients in severe OSAHS group were significantly higher than that of in the control,mild OSAHS group and moderate OSAHS group ( P ＜ 0.01 ).The levels of saturation of minimum oxygen from skin of patients in severe OSAHS group was significantly lower ( MSpO2 ) than in that of the control,mild OSAHS group and moderate OSAHS group.Multiple linear regression analysis showed that fasting plasma insulin and insulin resistance was positive correlation with apnea-hypopnea index,while they also negatively associated with saturation of minimum oxygen.Conclusions FIns and insulin resistance strongly associate with AHI and levels of saturation of minimum oxygen from skin.Hypertensive patients with OSAHS have more chances to suffer with insulin resistance.

With the development and application of microarray and high-throughput sequencing technology, it is possible to genomi-cally scan breast cancer associated CNV and SNPs. Multiple researches showed that the frequent aberrance of 8q24 was associated with breast cancer. Oncogenes such as MYC, PSCA and breast cancer associated loci are located in 8q24, and frequent amplification of 8q24 was proposed to be related with breast cancer development and prognosis. This review summarizes the association of the 8q24 amplification and SNPs with breast cancer by correlated genes on this locus.

Objective: To investigate the prognosis of patients who receive neoadjuvant chemotherapy (NAC) for invasive micropapillary carcinoma (IMPC) of the breast using a propensity score matching (PSM) method and to analyze the effects of NAC. Methods: Clinical and pathological data of a total of 251 cases of IMPC of the breast were collected for this study, from January 2011 to March 2014 in Tianjin Medical University Cancer Institute and Hospital, of which the NAC group comprised 67 cases and the non-NAC group comprised 184 cases. Tumor sizes before and after NAC were compared in the NAC group. Prognostic differences were compared between the NAC group and non-NAC group before and after PSM balancing the baseline. Results: The mean value of the maximum dimensions significantly reduced from 5.0cm to 4.2cm in the NAC group after NAC (P=0.035), but there was no statistically significant difference in T stage changes (P=0.064). A total of 49 pairs of patients were matched after PSM, and differences in the baseline data of the paired group were not significant. Univariate survival analysis showed no significant difference in the recurrence-free survival (RFS) rate between the NAC group (77.6% vs. 89.2%) and non-NAC group (72.1% vs. 91.0%) before and after PSM (all P>0.05). The 5-year distant metastasis-free survival (DMFS) rates in the NAC group before and after PSM were 53.4% and 50.0%, respectively, which were both significantly lower than those in the non-NAC group 69.1%, 59.2% (all P<0.05), and multivariate survival analysis showed that undergoing NAC was an independent prognostic factor of DMFS after PSM. Conclusion: Breast IMPC is a special type of tumor that is not sensitive to chemotherapy. Although some tumors decrease after NAC, IMPC patients do not benefit from NAC in terms of RFS; NAC may even increase the risk of distant metastasis. Therefore, IMPC patients should undergo surgical treatment as soon as possible, and NAC is not recommended.

Objective:To compare the differences in the delineation of the gross tumor volume (GTV) and lymph nodes of nasopharyngeal carcinoma (NPC) patients using computerized tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT), and to investigate the optimal standard uptake value (SUV; relative to the MRI-based delineation) for the automatic delineation of GTV using PET. Methods:A total of 53 NPC patients proposing to receive radiotherapy were selected for this study. The CT, MRI, and PET images of each patient were obtained before radiotherapy. Then GTV and positive lymph nodes were delineated on these three types of images. They were individually named GTV MRI, GTV CT, GTV PET2.5 (SUV=2.5), Lymph MRI, Lymph CT, and Lymph PET2.5 and compared. The GTV ∩2.5 (overlapped GTV) was obtained through the alignment of MRI and PET/CT images. Meanwhile, GTV was delineated on PET images using thresholds of SUV=4.0, 4.5, 5.0, and 5.6, obtaining GTV PET4.0, GTV PET4.5, GTV PET5.0, and GTV PET5.6. Then their volume and Dice similarity coefficients (DSCs) were compared. Results:Compared to GTV MRI, GTV CT decreased by 1.73% ( P>0.05) and GTV PET2.5 increased by 21.34% ( t=-3.52, P < 0.05) in the three types of images. The volume of Lymph PET2.5 was 1.61 and 1.87 times the volume of Lymph MRI and Lymph CT, respectively ( t=-4.12, -5.18; P< 0.05). The volume of high-SUV lymph nodes was 4.07 times the volume of lymph nodes with low SUVs or SUV=0 ( t=5.50, P< 0.05) on PET images. The DSC between GTV PET4.0and GTV MRI was 0.78 ± 0.27, which was lower than that between GTV PET2.5 and GTV MRI (0.84 ± 0.18). However, GTV PET4.0 approximated to GTV ∩2.5 ( P>0.05). Conclusions:Compared to CT and 18F-FDG PET/CT, MRI shows more accurate boundaries of GTV and lymph nodes. When 18F-FDG PET/CT was adopted to automatically delineate GTV, the GTV delineated using SUV=4.0 was closer to GTV MRI.

Objective To investigate the role and potential mechanisms of tumor necrosis factor alpha-inducible protein 8-like molecule 1(TNFAIP8L1)in acute liver injury in mice.Methods The second generation of C57BL/6J male wild-type(WT)mice and the C57BL/6J female TNFAIP8L1+/-mice and WT mice were selected to further self-breed the third generation of male TNFAIP8L1-/-mice and the third generation of WT male mice.Five normal third-generation male WT mice and five normal third-generation male TNFAIP8L1-/-mice were selected.The serum alanine aminotransferase(ALT)levels of the two types of normal mice were measured and compared.The infiltration of inflammatory cells and cell necrosis in the liver tissues of the two types of normal mice were observed after hematoxylin & eosin(HE)staining.Flow cytometry was used to detect the percentages of neutrophils(Neu),eosinophils(EOS),dendritic cells(DC),bone marrow-derived macrophages(BMDMs),and bone marrow-derived mononuclear cell(BMNCs)in the liver myeloid cell subsets of the two types of normal mice.Another 5 third-generation male WT mice and 4 third-generation male TNFAIP8L1-/-mice were selected to induce acute liver injury mouse models using lipopolysaccharide(LPS)/D-galactosamine(D-Gal).After 24 hours,the serum ALT levels of the two types of acute liver injury mice were detected and compared,the infiltration of inflammatory cells and cell necrosis in the liver tissues of the two types of acute liver injury mice were observed,and the percentages of Neu,EOS,DC,BMDMs and BMNCs in the liver myeloid cell subsets of the two types of acute liver injury mice were measured by using the above methods.Results There was no significant difference in the percentages of Neu,EOS,DC,BMDMs and BMNCs,and serum ALT levels in the livermyeloid cell subsets of normal WT mice and TNFAIP8L1-/-mice(P＞0.05).HE staining results of liver tissues in normal WT mice and TNFAIP8L1/mice showed that hepatic lobules were structurally complete and clear,hepatocytes were morphologically normal and arranged neatly,and there was no obvious inflammatory cell infiltration or cell necrosis.Twenty-four hours after acute liver injury,the percentages of Neu and BMNCs in the liver myeloid cell subsets and the serum ALT levels in the liver tissues of TNFAIP8L1-/-mice were significantly higher than those of WT mice(P＜0.05);there was no significant difference in the percentages of EOS,DC and BMDMs in the liver myeloid cell subsets of mice between the two groups(P＞0.05).In the liver tissues of WT mice with acute liver injury,hepatic lobules were structurally blurred,hepatocytes were swollen with scattered vacuolated steatosis,and a small amount of inflammatory cells were infiltrated.In the liver tissues of TNFAIP8L1/mice with acute liver injury,hepatic lobules were structurally non-existent,and hepatocytes were severely damaged and extensively necrotic,with a large amount of inflammatory cell infiltration.Conclusion The deficiency of the TNFAIP8L1 gene in mice does not affect the development of liver myeloid cells and the homeostasis of the liver.TNFAIP8L1 plays an inhibitory role in the occurrence and development of acute liver injury.TNFAIP8L1 gene deficiency aggravates LPS/D-Gal-induced acute liver injury,possibly by increasing Neu and BMNCs infiltration and recruiting other types of immune cells to infiltrate liver tissues,thereby exacerbating liver cell necrosis.

Objective:To investigate the influences and mechanism of extracellular vesicles from dermal papilla cells (DPC-EVs) of mice on human hypertrophic scar fibroblasts (HSFs).Methods:The study was an experimental research. The primary dermal papilla cells (DPCs) of whiskers were extracted from 10 6-week-old male C57BL/6J mice and identified successfully. The DPC-EVs were extracted from the 3 rd to 5 th passage DPCs by ultracentrifugation, and the morphology was observed through transmission electron microscope and the particle diameter was detected by nanoparticle tracking analyzer ( n=3) at 24 h after culture. The 3 rd passage of HSFs were divided into DPC-EV group and phosphate buffer solution (PBS) group, which were cultured with DPC-EVs and PBS, respectively. The cell scratch test was performed and cell migration rate at 24 h after scratching was calculated ( n=5). The cell proliferation levels at 0 (after 12 h of starvation treatment and before adding DPC-EVs or PBS), 24, 48, 72, and 96 h after culture were detected by using cell counting kit 8 ( n=4). The protein expressions of α-smooth muscle actin (α-SMA) and collagen typeⅠ (ColⅠ) in cells at 24 h after culture were detected by immunofluorescence method and Western blotting, and the protein expression of Krüppel-like factor 4 (KLF4) in cells at 24 h after culture was detected by Western blotting. After the 3 rd passage of HSFs were cultured with DPC-EVs for 24 h, the cells were divided into blank control group, KLF4 knockdown group, and KLF4 overexpression group according to the random number table. The cells in blank control group were only routinely cultured for 48 h. The cells in KLF4 knockdown group and KLF4 overexpression group were incubated with KLF4 knockdown virus for 24 h, then the cells in KLF4 knockdown group were routinely cultured for 24 h while the cells in KLF4 overexpression group were incubated with KLF4 overexpression virus for 24 h. The protein expressions of KLF4, α-SMA, and ColⅠ in cells were detected by Western blotting at 48 h after culture. Results:At 24 h after culture, the extracted DPC-EVs showed vesicular structure with an average particle diameter of 108.8 nm. At 24 h after scratching, the migration rate of HSFs in PBS group was (54±10)%, which was significantly higher than (29±8)% in DPC-EV group ( t=4.37, P<0.05). At 48, 72, and 96 h after culture, the proliferation levels of HSFs in DPC-EV group were significantly lower than those in PBS group (with t values of 4.06, 5.76, and 6.41, respectively, P<0.05). At 24 h after culture, the protein expressions of α-SMA and ColⅠ of HSFs in DPC-EV group were significantly lower than those in PBS group, while the protein expression of KLF4 was significantly higher than that in PBS group. At 48 h after culture, compared with those in blank control group, the protein expression of KLF4 of HSFs in KLF4 knockdown group was down-regulated, while the protein expressions of α-SMA and ColⅠ were both up-regulated; compared with those in KLF4 knockdown group, the protein expression of KLF4 of HSFs in KLF4 overexpression group was up-regulated, while the protein expressions of ColⅠ and α-SMA were down-regulated. Conclusions:The DPC-EVs of mice can inhibit the proliferation and migration of human HSFs and significantly inhibit the expressions of fibrosis markers α-SMA and ColⅠ in human HSFs by activating KLF4.