Breast cancer susceptibiIity gene 1( BRCA1)is a tumor suppressor,but mutated get BRCA1 is cIoseIy reIated to the deveIopment of breast cancer. Current study has reveaIed that BRCA1 can get invoIved in the DNA damage repair process as a key mediator. DNA doubIe-stranded break (DSB)is the most serious form in DNA Iesions,and BRCA1 pIays an important roIe in repairing DSB through reguIation of homoIogous recombination( HR). In this articIe,the moIecuIar mechanism of BRCA1 in reguIating HR is reviewed with reference to the activity of functionaI domains in BRCA1 struc-ture,the mutations occurring in main domains of BRCA1,the reIationship of BRCA1 with BRCA2, Rad51 or CtIP,and phosphoryIation of BRCA1. In addition,the association of the defective BRCA1-mediated HR repair mechanism with the sensitivity to different DNA damaging agents and synthetic IethaIity in tumor ceIIs is aIso addressed.

Objective To evaluate the therapeutic effect of transanal local excision in the treatment of low rectal cancer.Methods The data of 49 cases of low rectal cancer patients treated by transanal local excision (group A,37 cases of T1 patients and 12 cases of T2 patients) were reviewed retrospectively,and compared with the group of 45 cases treated by radical resection( group B,11 cases of T1 patients and 34 cases of T2 patients).The 5-year survival rates,recurrence rates and postoperative complications between the two groups were compared.Results The incidence of postoperative complications in group A was significantly lower than that in group B(4.1％ vs 15.6％,x2 =4.69,P ＜0.05 ).The 5-year survival rate of group A was 97.9％ and the 5-year survival rate of group B was 95.6％.There was no significantly statistical difference on the 5-year survival rate between the two groups( x2 =0.439,P ＞ 0.05 ).But for the T2 patients,the recurrence rates in group A was 33.3％,which was significantly higher than the T2 patients in group B(5.9％ ) ( x2 =5.89,P ＜0.05 ).All patients with low histopathological grade tumor in group A showed postoperative recurrence and metastasis.Conclusion Transanal local excision with a rigid criteria can get good curative effect in the T1 patients,but not suitable for the T2 patients or patients with low histopathological grade tumor.

BACKGROUND: Transfection is the most important beginning component of research about gene function. It is a problem to find a transfection agent with high efficiency and safety. Nanosized materials have high surface activity, are easy to be modified and easier to pass the biomembrane. Researchers are studying how to use nanosized materials as a transfection agent.OBJECTIVE: To study the transfection efficiency of different basic polymers with different molecular mass and degree of substitute, and to find the optimized transfection agent.DESIGN: Controlled study.SETTING: Institute of Genetic Engineering, Southern Medical University.METHODS: This study was performed in the Institute of Genetic Engineering, Southern Medical University from March 2006 to June 2007. Using the lipofectamine reagent as the positive control, we transfected siRNA (0.2 nmol/L), FITC-labeling targeting bcl-2, by nine nanometers (polylactic acid-polyglycolic acid, chitosan-poly-caprolactone, polyethyleneimin-macrogol) into leukemic cell K562 cultured without serum. Six hours post-transfection, 20% FBS serum was added. The cell proliferation was measured at 24, 48 and 72 hours by using the MTT method. After transfecting for 48 hours, the cells were collected to detect transfection ratio by using fluorescent microscopy, apoptosis ratio and expression of K562 and bcl-2 protein by flow cytometer (FCM). RESULTS: ① Fluorescence microscope detection showed there were significant differences of transfection efficiency between different materials (P < 0.05). Moreover there were statistical differences between different degrees of substitute, although they were the same material (P < 0.05). ② MTT method indicated the cell proliferation ratio was positively related to transfection ratio. ③ Flow cytometry results showed the suppression of expression of targeting gene and apoptosis ratio were positive correlated with transfection ratio. CONCLUSION:The nanometer poly-ethylene glycol combined with poly-ethylene imine (PEG-PEI), whose molecular mass is 1 800/2 000 and degree of substitute is 29%, has a high efficiency and low toxicity.

OBJECTIVE To study the effect of valproic acid ( VPA) on radiosensitivity to MCF7 breast cancer cells. METHODS MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 0, 24, 48 and 72 h respectively, irradiated with 8 Gy lR, and at 6 h post-lR, the γ-H2 AX foci formation in MCF7 cells was tested by immunofluorescence assay. MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 72 h, irradiated with 4 Gy lR, and at 48 h post-lR, the cell survival rate was detected by MTT assay. MCF7 cells were pretreated with VPA 0.5 mmol.L-1 for 24 h, and then irradiated according to the amount of cells: 2 Gy (500 and 1000 cells per plate), 4 Gy (2000 and 4000 cells per plate), 6 Gy (8000 and 16000 cells per plate), and the cloning efficiency was calculated. MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 0, 24, 48 and 72 h respectively and the cell cycle profile was analyzed via flow cytometry. RESULTS After treatment with VPA alone for 24 h, MCF7 cells showed a significant increase in the amount of γ-H2 AX foci formation ( P < 0. 01). lt was also found that VPA increased lR-induced γ-H2 AX foci formation, which obviously prolonged the pretreatment time of VPA(P<0.01) in a time-dependent manner(r=0.98, P<0.05). VPA 0.5 and 1 mmol.L-1 had the same effect on γ-H2 AX foci formation. Furthermore, VPA was able to cause a significant decrease in lR-induced clonogenic survival but an increase in lR-induced cytotoxicity by MTT assay. Also, VPA alone decreased the plating efficiency of MCF7 cells. However, the cycle profile of MCF7 cells treated with both VPA 0.5 and 1 mmol.L-1 was not changed. CONCLUSION Without affecting the cell cycle profile, both the safe and critical dose of VPA used in clinical epilepsy treatment can significantly increase the accumulation of DNA double strand breaks in the cells and sensitize the cells to lR treatment, suggesting that VPA can induce radio-sensitization of breast cancer cells.

Objective:To investigate the impact and mechanisms of TAM to the imbalance of Treg /Th17 in the Eoc microenvi-ronment.Mte hods:Build the in vitro M2 macrophage model ,which was like TAMs .Use flow cytometry to detect the difference of the Treg/Th17 before and after the co-culture of M2 macrophage and CD 4+T cells.Use Western bolt to detect the change of T cell transcription factor and ELISA to detect the IL-10 levels in the supernatant after co-culture.Use crystal violet methods to detect the influence to the ovarian tumor cell proliferation between the different co-culture supernatants and the Transwell to detect the influence to the ovarian tumor cell migration.Thus to analysis the how TAMs influence the imbalance of Treg/Th17 in Eoc microenvironments.R esults:①After coc-ultured with M2 macrophage ,the ratio of Treg/Th17 was( 0.76 ±0.33 ) significant increased compared with control (0.41±0.25) ,M0( 0.40±0.32) and M1(0.31±0.16) (P<0.05).②After co-cultured,the supernatant of M2 group has a significant ability to promote the proliferation of Skov-3 cells.After co-cultured for 1 day, the Skov-3 cell number of M2 group was 14 942.43 ±434.19 , which was significantly higher than the control group ( 12 445.57 ±179.34 ) and CD3/28 group (12 470.32±434.18)(P<0.001).After co-cultured for 2 days,the Skov-3 cell number of M2 group was 30 129.09±520.53 ,which was significantly higher than the control group (25 622.81±897.07) and CD3/28 group(25 721.62±1 808.60) (P<0.05).③After co -cultured with M2 macrophage , the Treg-specific transcription factor Foxp 3 increased ( P=0.047 ) compared with control and M 1 group .④After co-cultured with M2 macrophage for 3 days,the concentration of IL1-0 in the supernatant was(264.04±75.9)pg/ml, which was significantly higher than CD 3/28 group ( 60.89 ±46.54 ) pg/ml,M 0 group ( 44.81 ±32.93 ) pg/ml, M1 group ( 42.71 ± 26.09)pg/ml(P=0.001).Conclusion: M2 macrophage induces the increase of the radio of Treg /Th17 as well as the increase of Treg-specific transcription factor Foxp 3 and the decrease of Th17 -specific transcription factor ROR-γt.Meanwhile , the co-culture supernatant of M2 macrophage and CD4+T cell have the ability to promote the proliferation and migration of ovarian cancer cell ,the mechanism which ,may related to the IL -10 in the supernatant .

Objective To evaluate the role of via-anal ileus tube drainage in the therapy of acute low colorectal obstruction caused by cancer in elderly patients.Methods Totally 31 elderly patients with acute obstruction caused by colorectal cancer were treated by this modality.With the help of colonscopy and radiograph,the ileus tube was inserted into the proximal bowel of the obstructive side via anus.Then we irrigated and drain through the tube.At the same time we observed the patients' symptoms,abdominal girth,plain abdominal radiograph.After the relief of the acute obstruction,operations were processed.Results After 7-14 days treatment,the acute obstruction was relieved and emergency operation was avoided.The cure rate of 1-staged resection was 93.5％ (29/31),the rate of 1-staged anastomosis was 68.9％ (20/29),the rate of complication was 19.4％ (6/31),no anastomotic leakage and no perioperative death occurred.Conclusions The via-anal tube drainage in the treatment of the elderly patients with acute obstruction is safe,effective,and the trauma is small.It would be the first choice to relieve the acute obstruction in future.

Objective To evaluate the safety,feasibility and value of treating familial adenomatous polyposis (FAP) with laparoscopic assisted total colorectal resection.Methods Thirty six patients with familial adenomatous polyposis from June 2009 to May 2014 were reviewed retrospectively.16 FAP patients underwent laparoscopic assisted total colorectal resection and 20 FAP underwent traditional laparotomy.The clinical data,including short term follow up outcomes,safety,and recovery were analyzed retrospectively.Results Laparoscopic assisted total colorectal resection was performed successfully on 16 patients without severe complications.The mean operation time of the laparoscopic group was (178 ± 33) min,the mean operative blood loss (72 ± 30)ml in the laparoseopic group were not significantly different when compared with the mean operation time (159 ± 24) min and the mean operative blood loss (110 ± 50) ml in the conventional group.Incision length (5.6 ± 1.1) cm,the intestinal function recovery time (2.7 ± 0.9) d,hospital stay after surgery (8.1 ± 1.6) d in the laparoseopic group were significantly different when compared with incision length (15.8 ± 1.8) cm,the intestinal recovery time (3.8 ±0.9) d,hospital stay after surgery (9.9 ± 1.6) d in the conventional group (P ＜ 0.05).There was no severe complications in neither group nor local recurrence,distant nletastases or death found during the follow-up of 6-56 months.Conclusions Laparoscopic assisted total colorectal resection for FAP can be performed safely and effectively with the advantages of minimal invasion,quick recovery and good short term effect.

Objective To discuss the effects of electroacupuncture intervention in different acupoints of rats models with diarrhea type irritable bowel syndrome (D-IBS).Methods The rat models were established with acute and chronic stimulation. The rats were divided into the normal control group, model group, “Taichong” (LR3) + “Zusanli” (ST36) group, and “Tianshu” (ST25) + “Zusanli” (ST36) group. Electroacupuncture was applied to bilateral corresponding acupoints for 20 minutes, every other day for 7 times. The physical signs of each rat were observed. The contents of 5-HT, NE and CGRP in the rats’ plasma were detected by sandwich ELISA. Results Compared with the normal group, the contents of 5-HT and NE in the model group were obviously higher and the content of CGRP decreased (P<0.05). Compared with the model group, the contents of 5-HT and NE in all treatment groups were lower and the content of CGRP increased (P<0.05). There was no difference between the “Taichong” (LR3) + “Zusanli” (ST36) and “Tianshu” (ST25) + “Zusanli” (ST36) groups.Conclusion The mechanism of electroacupuncture may be realized through lowering the contents of 5-HT and NE in the model rats and increasing the content of CGRP to treat D-IBS.

Objective To explore humam cytomegalovirus(HCMV) encoded microRNAs during latent infection in order to help study HCMV virology and latent infection mechanisms.Methods A model of HCMV latent infection via THP-1 cells infected with HCMV was constructed.Deep-sequencing was performed using high-resolution Solexa sequencing platform.The secondary structure of the newly sequenced miRNA was predicted by RNAFold bioinformatics software. Results HCMV encoded various miRNAs during latent infection, including miR-US25-2-3p, miR-US25-2-5p, miR-UL112, miR-US25-1, miR-UL22A and PC-5p-148467 with a predicted length of 25 bp, named hcmv-miR-US33as-5p.Conclusion HCMV can express many types of miRNAs during latent infection.

Objective To study the effect of HCV receptors′sequence on virus entry based on the two-dimensional structure and via tandem expression of HCV receptors on mouse hepatocytes.Methods The construced recombinant expression vectors pCDH-hLDLR-hSR-BⅠ-hCD81-GFP, pCDH-hLDLR-hCD81-hSR-BⅠ and pCDH-hCLDN-1-hOCLN-DsRed were cotransfected into 293FT cells with package vectors.The collected recombinant lentivirus expressing hCLDN-1-hOCLN was concentrated and attacked mouse hepatocytes.The transgenic mouse hepatocytes with tandem overexpression of CLDN-1 and OCLN were established after G418-selection.The transduced cells LSCCO/Hepa1-6 and LCSCO/Hepa1-6 were sorted via flow cytometry and puro-G418-selection after recombinant lentivirus expressing hLDLR-hSR-BⅠ-hCD81 and hLDLR-hCD81-hSR-BⅠattacked Hepa1-6 respectively.The infectivity of transduced mouse hepatocytes LSCCO/Hepa1-6 and LCSCO/Hepa1-6 to HCV was analyzed via direct-infection of serum-derived virus.Furthermore, the effect of HCV receptors′sequence on virus entry was studied.Results Both LSCCO/Hepa1-6 and LCSCO/Hepa1-6 enhanced HCV-cell binding.The transduced mouse hepatocytes LSCCO/Hepa1-6 had more HCV endocytosis.Conclusion SR-BⅠhas priority over CD81 in HCV entry in the early stage.