OBJECTIVETo investigate the effect of 5-Aza-2'-deoxycytidine (5-Aza-dC) on TIP30 gene expression and the relationship between TIP30 expression and the sensitivity to 5-fluouracil (5-Fu) in colorectal cancer cells.

METHODSThe methylation profile of TIP30 gene in HCT116 colorectal cancer cells was determined by methylation-specific PCR. The levels of TIP30 mRNA and protein were determined by RT-PCR and Western blot after the 5-Aza-dC treatment. MTT assay was used to detect the chemosensitivity of HCT116 cells to 5-Fu.

RESULTSTIP30 gene displayed complete DNA methylation in the HCT116 cells without 5-Aza-dC pretreatment. After the 5-Aza-dC treatment for 3 days, only demethylating PCR amplification product was detected and TIP30 gene showed DNA demethylation. With the prolongation of the time of removal of 5-Aza-dC treatment, methylated and demethylated PCR amplification products were observed and TIP30 gene displayed both DNA methylation and DNA demethylation in the colorectal cancer cells. At the day 10 after removal of 5-Aza-dC, methylating PCR amplification product appeared and TIP30 gene showed DNA methylation. No expressions of TIP30 mRNA and protein were detected in the HCT116 cells untreated with 5-Aza-dC. After the treatment of 5-Aza-dC for 3 d and then removed the 5-Aza-dC, the expressions of TIP30 mRNA and protein were increased obviously. With the prolonged time after 5-Aza-dC removal, the expressions of TIP30 mRNA and protein decreased and reached the lowest level on day 10. The IC50 values of 5-Fu were 41.62, 33.17 and 4.96 µg/ml in the HCT116 cells pretreated with 5-Aza-dC, d0 and d10 with the drug removal after drug treatment for 3 d, respectively.

CONCLUSIONSThe results of this study show that the expression of TIP30 gene may be associated with its DNA methylation status and may affect the sensitivity of colorectal cancer cells to 5-Fu.

Acetyltransferases ; genetics ; metabolism ; Antimetabolites, Antineoplastic ; pharmacology ; Azacitidine ; analogs & derivatives ; pharmacology ; Cell Proliferation ; drug effects ; CpG Islands ; genetics ; DNA Methylation ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Fluorouracil ; pharmacology ; Gene Expression Regulation, Neoplastic ; HCT116 Cells ; Humans ; Inhibitory Concentration 50 ; RNA, Messenger ; metabolism ; Transcription Factors ; genetics ; metabolism

BACKGROUNDWhether the sequential treatment with bortezomib plus dexamethasone (BD) followed by autologous hematopoietic stem cell transplantation (ASCT) could extend the overall survival period in multiple myeloma patients is still not clear. Few large case studies about this therapeutics in multiple myeloma were reported in China. Our purpose was to assess the efficacy and adverse effects of sequential treatment with BD chemotherapy and ASCT in patients with multiple myeloma.

METHODSFifty-three patients with newly diagnosed or relapsed/refractory multiple myeloma received BD as induction therapy before ASCT. Stem-cell mobilization was undertaken with cyclophosphamide 3 - 5 g/m(2) plus granulocyte colony-stimulating factor 300 µg/d. Target yield was 2.0×10(6) CD34(+) cells/kg. Conditioning for ASCT consisted of melphalan 200 mg/m(2). Thalidomide and/or a-interferon was used as post-transplantation maintenance treatment.

RESULTSThe BD chemotherapy before transplantation was effective in 86.7% of the 53 patients, including 22.6% with complete remission (CR), 39.6% with near complete remission (nCR), and 24.5% with partial remission (PR). The best effect was achieved after two treatment courses. Most bortezomib-related adverse effects were classes 1 - 2. All patients were successfully mobilized after BD for autologous peripheral blood stem cell transplantation. The ASCT was effective in 96.3% of patients, including 49.1% with CR, 32.1% with nCR, and 15.1% with PR. The CR rate was significantly increased (49.1% vs. 22.6%, P < 0.05) by sequential ASCT. Within 27 (range, 6 - 53) months of follow-up, the efficacy of ASCT was maintained in 29 patients and further enhanced by post-transplantation maintenance treatment in four patients. Eleven patients died after transplantation. Among the patients undergoing BD/ASCT treatment, overall survival (OS) was significantly better in newly diagnosed patients in comparison to relapsed/refractory patients (P = 0.046).

CONCLUSIONSBD chemotherapy can be used as an induction therapy prior to ASCT in patients with multiple myeloma. Its rate of effectiveness is high and it alleviates symptoms quickly without affecting peripheral blood stem cell collection. The majority of adverse effects are mild (tolerable). Sequential BD with ASCT is the preferred option for transplant patients. First-line ASCT could prolong survival of newly diagnosed patients rather than delayed ASCT.

Adult ; Aged ; Boronic Acids ; administration & dosage ; adverse effects ; therapeutic use ; Bortezomib ; Dexamethasone ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; therapy ; Pyrazines ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the psychological impact of mastectomy on women with breast cancer.

METHODSQuestionnaires were answered by 90 patients after mastectomy for breast cancer. The data were collected and analyzed regarding the age, occupation, education, income and living place of the patients. Their psychological changes were compared and evaluated statistically using chi-square analysis.

RESULTSMastectomy caused psychological impact on half of the patients, which included fear of cancer, feeling of body incompleteness, inconvenience in working and social communication, less sexual act and low spirit. 79 percent of the patients considered breast reconstruction unnecessary. 54 percent did not know that the breast could be reconstructed. The patient feelings differed with the age, occupation, income and living place.

CONCLUSIONMastectomy hurts patient psychological health.

Age Factors ; Body Image ; Breast Neoplasms ; psychology ; surgery ; Chi-Square Distribution ; Fear ; Female ; Humans ; Mammaplasty ; psychology ; Mastectomy ; psychology ; Socioeconomic Factors ; Surveys and Questionnaires

Objective: To explore the nipple-areola complex blood supply mode in hypertrophic breasts, and to obtain the pertinent knowledge of vascular anatomy for breast reduction surgery as well as the analysis of similarities and differences between hypertrophic and normal breasts. Comparing the blood supply of nipples-areola complex between these two groups for analyzing their similarities and differences. Methods: Three dimensional reconstruction of the arteries in breast were performed in 50 patients between September 2015 and August 2017 with breast hypertrophy by computed tomographic angiography (CT angiography). The distribution pattern and the source direction of each main blood vessel was observed, counted and analyzed. Then, the data of breast hypertrophy patients were compared with the previous data about nipple-areola blood supply in normal population (the definition of main vessel: entering the breast gland or reaching the nipple-areola surrounding area, and diameter larger than 1 mm). Statistical description was taken for comparison. Results: 135 main vessels were observed in 100 breasts (50 patients). They mainly originate from the internal thoracic artery (69, 51.1%), lateral thoracic artery (37, 27.4%) and thoracoacromial artery(16, 11.9%), as well as a small amount from the brachial artery (7, 5.2%) and axillary artery(6, 4.4%). No main supply vessels from the posterior intercostal artery have been found. The patterns of breast blood supply varied among individuals, and high asymmetry ratio in the same individual was also observed. The internal superior (left: 30.7%, right: 34.2%) and superior lateral quadrant (Left: 29.2%, Right: 20%) of the breast was the most likely area for the main vessel to pass, followed by the breast lateral (Left: 16.9%, Right: 18.5%), lower inner (Left: 4.6%, Right: 5.7%), central (Left: 4.6%, Right: 4.2%), and superior (Left: 1.5%, Right: 2.8%). Differences existed in main vessels between normal breasts and hypertrophic breasts, either for source arteries or the distribution of breast. There was no main blood supply from the intercostal arteries or across the outer inferior quadrant. Conclusions The blood supply of the nipple-areola is not completely consistent between the hypertrophic breast and the normal size breast, and the blood supply pattern of the hypertrophic breasts is complex and diverse. CT angiography might be used before breast reduction surgery for clarifying the direction of the main vessels, so as to preserve more blood supply for nipple-areola, and to prevent nipple-areola necrosis.

BACKGROUNDAspergillus fumigatus (A. fumigatus) is a ubiquitous saprophytic fungus responsible for the majority of invasive mold infections in patients undergoing chemotherapy, organ transplantation or with persistent neutropenia. This study aimed to determine the role of E-cadherin for adhesion and endocytosis of A. fumigatus blastospores in the human epithelial cell line A549.

METHODSA. fumigatus blastospores were incubated with the total protein of A549 to investigate the binding of E-cadherin and blastospores followed by an affinity purification procedure. After establishing the adhesion model, the adhesion and endocytosis of A. fumigatus blastospores by A549 cells were evaluated by down-regulating E-cadherin of A549 cells using blocking antibody or small interfering RNA (siRNA).

RESULTSE-cadherin was adhered to the surface of A. fumigatus blastospore. Adhesion and endocytosis of the blastospores were reduced by blocking or down-regulating E-cadherin in A549 cells.

CONCLUSIONSE-cadherin is a receptor for adhesion and endocytosis of A. fumigatus blastospores in epithelial cells. This may open a new approach to treat this fungal infection.

Aspergillus fumigatus ; cytology ; Cadherins ; genetics ; metabolism ; Cell Line ; Endocytosis ; physiology ; Epithelial Cells ; metabolism ; microbiology ; Fungal Proteins ; chemistry ; metabolism ; Humans ; In Vitro Techniques ; Protein Binding ; physiology ; RNA, Small Interfering ; Spores, Fungal ; cytology

OBJECTIVETo establish cut offs and risk stratification of dyslipidemia in Chinese adults.

METHODSData from 2 widely cited studies: the PRC-US Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology and the China Multi-Provincial Cardiovascular Cohort Study, with a total of 40 719 Chinese adults, age 35 to 64 at baseline, about half men and half women, followed up for a total of 345 140.5 person years, were used to analyze the relationship between dyslipidemia and ischemic cardiovascular diseases (ICVD, including coronary heart events and ischemic stroke events) using a common data analysis protocol co-developed by the scientists from the 2 studies. The relative risk was estimated with the Cox proportional hazard model adjusting for other conventional cardiovascular risk factors. The 10-year absolute risk of ICVD for a 50 years-old person at different risk factor combinations was used to develop the risk stratification.

RESULTS(1) There was a continuous linear relationship between baseline TC (or LDL-C) and ICVD risk without a threshold; (2) The incidence (absolute risk) of ICVD was similar for LDL-C < 3.37 mmol/L (130 mg/dl) and for TC < 5.18 mmol/L (200 mg/dl); and similar for LDL-C < 4.14 mmol/L (160 mg/dl) and for TC < 6.22 mmol/L (240 mg/dl); (3) The absolute ICVD risk for TC > or = 6.22 mmol/L (240 mg/dl) was slightly less but close to that for grade 1 hypertension; (4) ICVD risk increased as HDL-C decreased; (5) No significant association was found between baseline TG and subsequent ICVD; (6) At any TC level, the absolute ICVD risk for those having only hypertension was higher than that for those having 3 other risk factors.

CONCLUSIONThe cut offs for diagnosis of dyslipidemia in Chinese adults can refer to those used in relevant international guidelines: TC < 5.18 mmol/L (200 mg/dl) [or LDL-C < 3.37 mmol/L (130 mg/dl)] as normal, TC 5.18 - 6.19 mmol/L (200 - 239 mg/dl) [or LDL-C 3.37 - 4.12 mmol/L (130 - 159 mg/dl)] as borderline high, and TC > or = 6.22 mmol/L (240 mg/dl) [or LDL-C > or = 4.14 mmol/L (160 mg/dl)] as high; HDL-C < 1.04 mmol/L (40 mg/dl) as low, 1.04 - 1.53 mmol/L (40 - 59 mg/dl) as normal and > or = 1.55 mmol/L (60 mg/dl) as optimal. In risk stratification scheme, hypertension plays a role that equals to that of any other 3 risk factors.

Adult ; China ; epidemiology ; Cohort Studies ; Dyslipidemias ; diagnosis ; epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Myocardial Ischemia ; diagnosis ; epidemiology ; Risk Assessment ; Risk Factors

Objective:To study the effects of licochalcone A （LCA） on the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes （MH7A） as well as the related inflammatory factors， also to reveal the relevance between mitogen activated protein kinase （MAPK） signaling pathway and LCA regulation of MH7A cell proliferation and apoptosis. Method:MH7A cells were cultured and divided into blank group， LCA groups （10，20，40 μmol·L^-1）. The proliferation of MH7A cells was detected by methylthiazolyldiphenyl-tetrazolium bromide（MTT）and immunofluorescence staining. The cell cycle of MH7A cells was determined by flow cytometry after PI staining and apoptosis was detected by flow cytometry after Annexin V/PI staining. The effect of LCA on interleukin-1β（IL-1β） mRNA was detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. Western blot was used to detect the effect of LCA on the key proteins of MAPK signaling pathway， meanwhile， PD98059， a specific ERK inhibitor， was used to observe the expression levels of p-ERK and IL-1β. Result:Compared with blank group， LCA could inhibit the proliferation of MH7A cells in a dose-dependent manner， and the number of living cells decreased significantly（P<0.01）， while the number of early apoptotic cells increased significantly（P<0.01）. Compared with the tumor necrosis factor-α （TNF-α，10 μg·L^-1）group， LCA could reverse the expression of IL-1β mRNA induced by TNF-α（P<0.01）. and compared with the blank group， LCA also promoted the phosphorylation of ERK， JNK and p38 in a dose-dependent manner（P<0.01）. After ERK inhibitor PD98059 inhibited ERK phosphorylation， the inhibitory effect of LCA 10， 20 μmol·L^-1 on IL-1β disappeared. Conclusion:LCA can inhibit the proliferation and induce apoptosis of MH7A cells， which may be related to the phosphorylation of MAPK pathway related proteins， and then inhibit the expression of inflammatory factors.