The DNA damage response is critical for cells to maintain genome stability and survival. In this review, we discuss approaches to targeting critical elements of the DNA damage response for radiosensitization and chemosensitization. In addition, we also discuss strategies for targeting DNA damage response and DNA repair defects in cancer cells for synthetic lethality.
Antineoplastic Agents ; therapeutic use ; Cell Death ; DNA Damage ; genetics ; DNA Repair ; genetics ; Dose-Response Relationship, Radiation ; Drug Resistance, Neoplasm ; Genomic Instability ; Humans ; Neoplasms ; drug therapy ; genetics ; pathology ; radiotherapy ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases ; pharmacology ; Radiation Dosage

OBJECTIVETo critically assess the quality of literature about systematic review or meta-analysis on traditional Chinese medicine (TCM) published in Chinese journals.

METHODSElectronic searches in CNKI, VIP and Wanfang data-base were conducted to retrieve the systematic reviews or meta-analysis reports on TCM, including herbal medicine, needling, acupuncture and moxibustion, as well as integrative medicine, they were identified and extracted according to the 18 items of QUOROM (quality of reporting of meta-analyses) Statement and relative information. The appraisal was made taking the indexes mainly including objectives, source of data, methods of data extraction, quality assessment of the included studies, measurement data synthesis, etc.

RESULTSEighty-two systematic reviews were identified, except 6 reviews were excluded for repeatedly published or didn't comply with the enrolled criterion, 76 reviews concerning 51 kinds of diseases were enrolled for appraisal. Among them, 70 reviews evaluated the efficacy of TCM, mainly on Chinese herbs and 9 on acupuncture and moxibustion. In majority of the reviews, randomised controlled trials were included and the data resources were described, but in 26 reviews only the Chinese databases were searched and the description about data extraction and analysis method were too simple; and 70% of reviews assessed the quality of the included studies; none used flow chart to express the process of selection, inclusion and exclusion of studies.

CONCLUSIONSFew reviews or Meta-analysis reports reached the international standard and there is insufficient description of methodology for conducting systematic reviews, so it is hardly to be repeated. The authors suggested that advanced methodological training is necessary for reviewers.

Acupuncture Therapy ; China ; Evidence-Based Medicine ; Humans ; Medicine, Chinese Traditional ; Meta-Analysis as Topic ; Periodicals as Topic ; standards ; Quality Control ; Review Literature as Topic

Background Hypoxia is a crucial factor of neovascularization.Many researches found that stromal cell-derived factor-1 (SDF-1) and integrin-linked kinase (ILK) play an important role in the neovascular disease.However,effect of SDF-1 and ILK in eye neovascular disease is below understood.Objective The aim of this study was to investigate the effect of hypoxia on the expressions of SDF-1 and ILK in cultured retinal pigment epithelium(RPE) cells in vitro.Methods RPE tissue was isolated from 4-week-old C57BL/6 mouse and was digested and cultured in DMEM/F12 with 10％ fetal bovine serum (FBS).The cells with 80％ confluence were collected and passaged.The third generation of cells were identified with cytokeratin 18 (CK18) antibody by immunochemistry.The cells were inoculated at the density of 5×104 cells/ml to free-serum DMEM/F12 for 24 hours and then were cultured in regular medium in the normoxic control group.RPE cells were cultured for 1 hour and 3,6,12,24,48,72 hours with 200 μmol/L CoCl2 in the hypoxia group.Reverse transcription-PCR(RT-PCR) was used to evaluate the expressing change of SDF-1 mRNA and ILK mRNA in RPE cells,and Western blot was used to assay the expressing change of SDF-1 protein and ILK protein in RPE cells in different time points.The detected outcomes were represented as the ratio of target gene A value/β-actin A value.Results Cultured cells showed the polygon in shape with the black pigment granules in cytoplasm.Over 90％ cells were positive response for CK18.Expressions of the SDF-1 mRNA and ILK mRNA were increased in different time points after CoCl2 co-cultured(SDF-1 mRNA:F=281.875,P=0.000 ;ILK mRNA: F=187.566,P=0.000),with the highest expressing value in hypoxia at 12 hours.No significant change in the expression of SDF-1 mRNA and protein was found 1 hour after CoCl2 co-cultured,but expressions of SDF-1 mRNA and ILK mRNA were significantly higher in 3,6,12,24,48 and 72 hours than the normoxic control group(P＜0.01).The expressions of SDF-1 protein and ILK protein were gradually ascended with the time increase of CoCl2 co-culture,showing a significant difference among different time points(SDF-1: F=44.719,P =0.000 ; ILK: F =144.481,P =0.000),and the up-regulation of SDF-1 protein and ILK protein expression was seen mainly in 3,6,12,24,48 and 72 hours after CoCl2 co-cultured in comparison with the normoxic control group (P＜0.01).Conclusions SDF-1 and ILK are involved in the hypoxic response of RPE cells and may play a potential role in ischemic/hypoxic retinopathy.

Background Researches showed that as the non-optical factors,cognitive has certain influence on the regulating system.So accurately experimental design is one of the key steps that evaluates the non-optical factors on regulating system.Objective The present study was to investigate the influence of presenting pattern of target and watching way on the level and amplitude of accommodative fluctuate and to analyze the effect of focus gaze of cognitive on regulating system and the relationship between focus gaze condition under near work and the development of myopia.Methods This study complied with Declaration of Helsinki,and the permission of Ethic Committee and written informed consent was obtained before entering in this trial.Thirty healthy volunteers were included with the mean age (24.80 ± 1.98) years old,equivalent refractive diopter (-1.92 ± 2.02) D and mean cylinder (-0.19±0.58) D.The presenting pattern of the targets was designed as focus gaze and relaxed gaze.The accommodative response and accommodative fluctuation in the complete corrected right eyes for the different targets at the 40 cm under the gazing state was recorded with Grand Seiko WAM 5500 automatic infrared refractor in the experiment.Results The mean accommodative response value was (1.86±0.26) D under the focus gaze and (1.27±0.39) D under the relax gaze,showing a statistically significant difference (t=-8.052,P=0.000).The mean fluctuate value was(0.17±0.06) D under the focus gaze,with a significant lowing in comparison with (0.28±0.17) D under the relax gaze (t =3.600,P =0.001).Conclusions These results demonstrate that the different presenting patterns of sighting target and watching ways of the subjects affect accommodation system.The accommodative response was relatively more accurate with a smaller microwavc moving under the focus gaze condition.

Objective:To investigate the expression of aromatase of renal tissue in systemic lupus erythematosus(SLE)model mice.Methods:BALB/c mice were induced SLE with homologuous splenic cell activated with ConA after being ovariectomized,and in the same time administered different doses of benzestrofol.E2 in peripheral blood and renal tissue was detected by ELISA and the expression of mRNA of aromatase in renal tissue was detected by RT-PCR in the 4th,6th,8th and 10th weeks.Results:The level of E2 of peripheral blood and renal tissue of SLE model mice became higher as benzestrofol exogenously administered heightened.Compared with control mice,the level of E2 in SLE model mice increased,and the expression of mRNA of aromatase of renal tissue increased with E2 increment.Conclusion:E2 promotes development of SLE through regulating expression of aromatase mRNA.

Background Corneal neovascularization (CNV) is an important cause of visual impairment and graft rejection after allograft corneal transplantation in inflammatory corneal diseases. The mechanisms and therapy relating to CNV are intensely investigated at all times. Objective This study was to evaluate the effect of eicosapentaenoic acid (EPA) on CNV induced by alkali cauterization and its mechanism. Methods The animal models of corneal neovasculation were induced in the right eyes in 72 Sprayue-Dawley rats by putting a piece of 3 mmfilter paper with 1 mol/L NaOH at the center of the cornea for 30 seconds. The rats were then divided randomly into the 0.02 mg EPA treatment group (24 rats) ,0.03 mg EPA treatment group (24 rats) ,model group (24 rats) and normal group (6 rats). EPA of 0.04 ml with doses of 0.02 mg or 0. 03 mg or saline solution of 0. 04 ml was injected subconjunctivally in model rats and immediately after cauterization. The presence of CNV and corneal edema were observed daily by slit lamp biomicroscope. 1,4,7 and 14 days after operation, corneal histopathological examination was performed by hematoxylin and eosin staining. The vascular endothelial cells were stained with CD34 by immunohistochemistry,and the expression of IL-1α,IL-6 mRNA and the nuclear factor-κBp65 ( NF-κBp65 ) proteins was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The use of animals complied with the Regulations for the Administration of Affair Concerning Experimental Animals by Hebei Province( version 1998 ). Results Under the slit lamp, CNV grew slowly from days 2-4 with obvious corneal edema and defect of epithelium. Larger CNV area and less edema were seen from days 7-10. Maximal vessel growth was observed 14 days after injury with thinner vessels in the model group. Histological examination showed that part of the corneal epithelium was damaged;serious corneal edema, more inflammatory cells and a lot of CNV in the stroma were presented in the model group. However, repairing of the corneal epithelium without CNV ,light corneal edema and less inflammatory cells were found in both the 0. 02 mg EPA and 0. 03 mg EPA treatment groups 7 days after alkali cauterization. The relative area of CNV in the 0. 02 mg EPA treatment group was ( 15.80±6.43 )% and ( 11.06±2. 14)% ,and that in the 0. 03 mg EPA treatment group was (16. 10±7.41 )% and (11.06±2. 51 )%, showing significant reduction in comparison with the model group [ (84. 74±7.77)% and (89.63±7.50) % ] 7 days and 14 days after operation ( P＜0. 05 ). Stronger expression of CD34 in the vascular endothelial cells of the cornea stroma was observed in the model group and an absence of CD34 was observed in the EPA-treated groups on the 7th day. RT-PCR revealed that the expression of IL-1α mRNA and IL-6 mRNA was lower in the EPA treatment groups than the model group ( P＜0. 05 ), and Western blot analysis showed that the expression of NF-κB/p65 in the corneas in the EPA treatment groups was significantly lower than that in the model group on the 4th day after operation (P＜0.05).Conclusion Topical application of EPA suppresses CNV induced by alkali burn possibly by inhibiting the expression of NF-κB,IL-1α and IL-6.

Objective: To investigate the prevalence of anxiety and depression among inpatients with AIDS and its influencing factors, so as to provide the evidence for improving the psychological health among inpatients with AIDS. Methods: The inpatients with AIDS that were hospitalized in an infectious disease hospital in Chengdu City were recruited using the convenient sampling method. The demographic features, depression and anxiety were collected using a self-designed questionnaire, Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale ( SDS ), respectively, and factors affecting the development of depression and anxiety were identified using a multivariable linear regression model among inpatients with AIDS. Results: The 228 AIDS inpatients included 186 men (81.58%) and 42 women ( 18.42% ), and had a mean age of ( 48.04±16.03 ) years. There were 113 inpatients ( 49.56% ) with a CD4+T cell count of ≤200 cells/μL, and the mean SAS and SDS standardized scores were 35.87±8.01 and 42.07±11.08 among AIDS inpatients, which were both significantly greater than in normal populations ( P<0.05 ). The prevalence rates of anxiety, depression, and comorbid anxiety and depression were 5.26%, 16.23% and 4.82% among the participants, respectively. Multivariable linear regression analysis identified unemployment as a risk factor of anxiety ( β'=0.168, P<0.05 ), and CD4+T cell count as a risk factor of anxiety ( β'=-0.151, P<0.05 ) and depression ( β'=-0.238, P<0.05 ) among inpatients with AIDS. Conclusions Anxiety and depression are prevalent among inpatients with AIDS. Unemployment and a low CD4+T cell count may cause a rise in the risk of developing anxiety and depression among inpatients with AIDS.

Objective To investigate the iodine nutritional level and thyroid function of pregnant and lactating women in rural areas of Jilin province. Methods The investigation sites were selected from rural areas of three towns (Baoshan, Mingcheng and Yantongshan of Panshi county, Jilin province) in 2009. The pregnant and lactating women were selected as subjects in these three towns. The blood samples were collected and the thyroid function (including serum TT3, TT4, FT3, FT4) were measured with chemiluminescence, and serum thyroglobulin antibodies(TgAb), thyromicrosome antibody(TMAb), and thyroglobulin(Tg) were measured with radioimmunoassay (RIA). The urine samples were collected three times within one month and were measured for iodine concentration by As-Ce catalytic spectrophotometry method. Results In the pregnant women, serum TT3 was higher than that of healthy pregnant women, accounted for 14.3%(8/56), while serum TT4, TT3, FT4 were lower than those of healthy pregnant women, accounted for 3.6%(2/56),5.4% (3/56), and 1.8%(1/56), respectively. In the lactating women,serum TT3 was higher than that of healthy lactating women, accounted for 3.6%(2/56), while serum TT4, FT4 were lower than those of healthy lactating women, accounted for 1.8%(1/56), respectively. Five per cent to 20% of the pregnant and lactating women had higher TgAb and TMAb. Conclusions Existing salt iodine level is appropriate for pregnant women and lactating women, but there was a tendency towards hypothyroid in some women. Routine monitoring of urinary iodine and thyroid function should be carried out among pregnant and lactating women.

Objective To know the prevalence tendency of Keshan disease(KSD) under control after 10 years in Shaanxi Province, the factors that causes or relative to the disease, to provide scientific reference for disease's prevention and control. Methods Through stratified cluster sampling, based on the severity of KSD in endemic area of Shaanxi Province, 12 villages from 6 counties were randomly selected as investigation points in 2006. The people older than 3 year-old were chosen to do clinical check up and electrocardiogram tracing. Among them, suspicious or abnormal cases were asked to take chest X-ray and cardiac ultrasound. Maize and rice, hair and whole blood were randomly collected to test the selenium content, the activity of Glutathione peroxidase (GSH-Px). Results The total detection rate of potential or chronic KSD was 2.44%(139/5694), the detection rate of abnormal ECG was 9.19% (523/5692), the detection rate of cardiac enlargement from chest X-ray and cardiac ultrasound were 45.6%(72/158) and 34.5%(59/171) respectively. The average content of selenium in staple foods(wheat and corn) were[(0.045±0.036), (0.035±0.025)mg/kg, respectively]. The level of hair selenium in patients and healthy people were [(0.376±0.091), (0.384±0.077)mg/kg, respectively], with non-significant different (u=0.77, P>0.05). There were significant differences in whole blood selenium of patients, healthy people in KSD areas and healthy people in non-KSD areas[(0.071±0.017), (0.077±0.017), (0.090±0.016)mg/L, respectively; F=4.55, P<0.05), the whole blood selenium in patients lower than in healthy people in KSD areas (P<0.05), in healthy people in KSD areas lower than in non-KSD areas (P<0.05). Conclusions After the KSD condition being controlled, the situation in Shaanxi Province has become stable and exhibited a decreasing tendency. The selenium level of both internal and external environment in the endemic area increased significantly, that is the main factors of controlling disease.