The cancer-testis gene,MEIOB,sensitizes triple-negative breast cancer to PARP1 inhibitors by inducing homologous recombination deficiency

Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of MEIOB.Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC.The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro.Patient-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.Results:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially TNBCs.Its activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells.Further analysis showed that MEIOB participated in DSB repair in TNBCs.However,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with YBX1.Furthermore,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX models.Conclusions:MEIOB played an oncogenic role in TNBC through its involvement in HRD.In addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.     

不同分期慢性肾脏疾病女性妊娠结局及预后的危险因素分析

目的:探讨妊娠与慢性肾脏疾病(CKD)的相互影响,分析不同分期CKD孕妇的妊娠结局及预后的危险因素。方法:回顾性分析2004年1月至2015年12月在北京大学第一医院妇产科进行产前保健、资料完整且合并CKD孕妇(共267例)的临床资料,分析不同分期CKD孕妇的临床资料及妊娠结局。对入组CKD孕妇进行产后随访,分析不同分期CKD孕妇的妊娠结局差异及预后的危险因素。结果:(1)与CKD 1期比较,CKD 3期和4期孕妇的早产和低出生体质量儿发生率明显升高(P0.05)。(2)妊娠早期CKD分期越高,产后肾功能恶化风险越大(CKD 2期HR=5.918,P=0.009;CKD 3和4期HR=8.336,P=0.008)。(3)妊娠早期尿蛋白定量≥1 g(HR=5.248,P=0.006)是CKD女性产后新发高血压的危险因素。结论:(1)晚期CKD孕妇的早产率及低出生体质量儿发生率较CKD 1期升高。(2)妊娠早期CKD分期越高,产后肾功能恶化风险越大;妊娠早期尿蛋白定量对CKD孕妇产后新发高血压有重要影响。     

Leukoaraiosis is associated with clinical symptom severity,poor neurological function prognosis and stroke recurrence in mild intracerebral hemorrhage:a prospective multi-center cohort study

Leukoaraiosis(LA)results from ischemic injury in small cerebral vessels,which may be attributable to decreased vascular density,reduced cerebrovascular angiogenesis,decreased cerebral blood flow,or microcirculatory dysfunction in the brain.In this study,we enrolled 357 patients with mild intracerebral hemorrhage(ICH)from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission,neurological function prognosis at 3 months,and 1-year stroke recurrence.Patients were divided into groups based on Fazekas scale scores:no LA(n=83),mild LA(n=64),moderate LA(n=98)and severe LA(n=112).More severe LA,larger hematoma volume,and higher blood glucose level at admission were associated with more severe neurological deficit.More severe LA,older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months.In addition,moderate-to-severe LA,admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence.These findings suggest that LA severity may be a potential marker of individual ICH vulnerability,which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH.Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols.This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University(approval No.12)on March 10,2011.     

Cover story

It is well known that the tumor microenvironment is quite different from that of the healthy surrounding tissues.Herein,novel environment—responsive drug delivery systems have recently been springing up for targeted cancer therapy.These drug delivery systems are based on the concept of"magic bullet"and composed of two parts:1)a core carrier(silicon or liposome or micelles)containing therapeutic drug;2)the sensitive part consist of sensitive polymers or sensitive     

Bacterial and yeast flora of root surface caries in elderly,ethnic Chinese

OBJECTIVES: Root caries is emerging as a significant problem in the middle aged and elderly. As little data is available on the microbiology of root caries in Chinese cohorts, we evaluated 30 such lesions in elderly, institutionalized, ethnic Chinese. METHODS: Samples of carious dentine were aseptically taken from root caries lesions of 18 subjects (five males and 13 females, mean age 79.67 +/- 8.57). The cultivable bacteria, both aerobic and anaerobic, were isolated and identified using standard methods and commercial identification kits. The yeasts were isolated on Sabouraud's agar and identified using the API system. RESULTS: The main findings were: (1) of the total isolates, 91.09% were Gram-positive and 8.91% were Gram-negative microorganisms; (2) the proportions of cocci and rods were 36.68 and 63.31%, respectively; (3) the predominant groups of organisms isolated were Streptococcus spp., Lactobacillus spp., Staphylococcus spp. and Actinomyces spp. with isolation frequencies of 100, 90.00, 73.33 and 63.33%, respectively; (4) the isolation frequency of yeasts belonging to Candida spp. (63.33%) was notably high although the proportion of yeasts within each sample was low (0.01%). Candida dubliniensis, a newly identified yeast species particularly prevalent in HIV infection, comprised 14.29% of yeasts. CONCLUSIONS: This study provides baseline information on the microbiologic features of root caries in the elderly, ethnic Chinese. Whilst our data on the most predominant bacteria isolated in root caries concur with those from other regions of the world the isolation of C. dubliniensis from these lesions has not been documented before.     

Retention in plaque and remineralization of enamel lesions by various forms of calcium in a mouthrinse or sugar-free chewing gum

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) nanocomplexes incorporated into sugar-free chewing gum have been shown to remineralize enamel subsurface lesions in situ. The aim of this study was to compare the ability of CPP-ACP, with that of other forms of calcium, to be retained in supragingival plaque and remineralize enamel subsurface lesions in situ when delivered in a mouthrinse or sugar-free gum in randomized, double-blind trials. In the mouthrinse study, only the CPP-ACP-containing mouthrinse significantly increased plaque calcium and inorganic phosphate levels, and the CPP were immunolocalized to the surfaces of bacterial cells as well as the intercellular matrix. In the chewing gum studies, the gum containing the CPP-ACP, although not containing the most calcium per piece of gum, produced the highest level of enamel remineralization independent of gum-chewing frequency and duration. The CPP could be detected in plaque extracts 3 hrs after subjects chewed the CPP-ACP-containing gum. The results showed that CPP-ACP were superior to other forms of calcium in remineralizing enamel subsurface lesions.     

Placement and replacement of restorations in general dental practice in Iceland

Ninety-one Icelandic practicing dentists (51% response rate) provided information related to the reasons for placement and replacement of 8,395 restorations and 741 sealants in 5,997 patients. Information included the patient's gender and age, the clinician's gender and experience in years since graduation, the defined criteria for replacement of restorations, the estimated past use of material in five-year increments and the records of 100 consecutively placed restorations. The materials used include composite (52.7%), amalgam (29.2%), glass ionomer (9.5%), resin-modified glass ionomer (7.1%) and other materials (1.4%). Although material selection was independent of the clinician's gender, female patients received more composite and fewer amalgam restorations than their male counterparts. Reasons for placing restorations comprised replacement of failed restorations (47.2%), primary caries (45.3%) and non-carious defects (7.5%). Secondary caries was the main reason for replacement for all types of restorations. Chi square analysis related to the dependence between the reasons for replacement and clinician's experience showed that more experienced clinicians recorded a lower frequency of secondary caries than less experienced ones (p<0.0001), while the diagnoses of discoloration and fracture of restorations increased with the clinicians' experience (p<0.0001).     

Repair strength of dental amalgams

This study tested the hypothesis that newly triturated amalgam condensed vertically on old amalgam was essential for establishing a bond between the new and old amalgams. Twelve rectangular bars were prepared with Dispersalloy and Tytin to establish their baseline flexure strength values. An additional 12 specimens were made and separated into 24 equal halves. All fracture surfaces were abraded with a flat end fissure bur. Twelve surfaces were paired with the original amalgam, and the remaining 12 surfaces were repaired with a different amalgam. At first, freshly triturated amalgam was condensed vertically on the floor of the specimen mold (Group A). The majority of specimens repaired with Group A failed to establish bond at the repair interface. All repair surfaces were abraded again and prepared by a second method. A metal spacer was used to create a four-wall cavity to facilitate vertical condensation directly on the repair surface (Group B). The specimens were stored in ambient air for seven days prior to flexure testing. The strength of specimens repaired with Group B ranged from 26% to 54% of the baseline specimens. ANOVA showed that amalgams repaired with a different amalgam yielded higher strength values than those repaired with the original amalgam, and the baseline specimens exhibited significantly higher strength values than all the repaired specimens.     

The application of mini-implants for orthodontic anchorage

The aim of this study was to explore the use of mini-implants for skeletal anchorage, and to assess their stability and the causes of failure. Forty-five mini-implants were used in orthodontic treatment. The diameter of the implants was 2mm, and their lengths were 8, 10, 12 and 14mm. The drill procedure was directly through the cortical bone without any incision or flap operation. Two weeks later, a force of 100-200g was applied by an elastometric chain or NiTi coil spring. Risk factors for the failure of mini-implants were examined statistically using the Chi-square or Fisher exact test as applicable. The average placement time of a mini-implant was about 10-15min. Four mini-implants loosened after orthodontic force loading. The overall success rate was 91.1%. The location of the implant was the significant factor related to failure. In conclusion, the mini-implants are easy to insert for skeletal anchorage and could be successful in the control of tooth movement.     

Fluoride and casein phosphopeptide-amorphous calcium phosphate

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) slows the progression of caries and remineralizes enamel subsurface lesions. The aim of this study was to determine the ability of CPP-ACP to increase the incorporation of fluoride into plaque and to promote enamel remineralization in situ. Randomized, double-blind, cross-over studies involved mouthrinses and dentifrices containing CPP-ACP and fluoride. The mouthrinses were used for 60 sec, three times/day for 5 days, and supragingival plaque was collected and analyzed for F. The dentifrices were rinsed as a water slurry for 60 sec four times/day for 14 days in an in situ model. The addition of 2% CPP-ACP to the 450-ppm-F mouthrinse significantly increased the incorporation of fluoride into plaque. The dentifrice containing 2% CPP-ACP produced a level of remineralization similar to that achieved with a dentifrice containing 2800 ppm F. The dentifrice containing 2% CPP-ACP plus 1100 ppm F was superior to all other formulations.