OBJECTIVES:Observational studies have shown that colonoscopy reduces colorectal cancer (CRC) incidence and mortality in the general population. We aimed to conduct a meta-analysis quantifying the magnitude of protection by colonoscopy, with screening and diagnostic indications, against CRC in patients with non-malignant findings and demonstrating the potentially more marked effect of screening over diagnostic colonoscopy.METHODS:PubMed, EMBASE, and conference abstracts were searched through 30 April 2015. The primary outcomes were overall CRC incidence and mortality. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effect models.RESULTS:Eleven observational studies with a total of 1,499,521 individuals were included. Pooled analysis showed that colonoscopy was associated with a 61% RR reduction in CRC incidence (RR: 0.39; 95% CI: 0.26–0.60; I2=93.6%) and a 61% reduction in CRC mortality (RR: 0.39; 95% CI: 0.35–0.43; I2=12.0%) in patients with non-malignant findings, although there was high heterogeneity for the outcome of CRC incidence. After excluding one outlier study, there was low heterogeneity for the outcome of incidence (I2=44.7%). Subgroup analysis showed that the effect of screening colonoscopy was more prominent, corresponding to an 89% reduction in CRC incidence (RR: 0.11; 95% CI: 0.08–0.15), in comparison with settings involving diagnostic colonoscopy (RR: 0.51; 95% CI: 0.43–0.59; P<0.001).CONCLUSIONS:On the basis of this meta-analysis of observational studies, CRC incidence and mortality in patients with non-malignant findings are significantly reduced after colonoscopy. The effect of screening colonoscopy on CRC incidence is more marked than diagnostic colonoscopy.

The acquisition of temozolomide resistance is a major clinical challenge for glioblastoma treatment. Chemoresistance in glioblastoma is largely attributed to repair of temozolomide-induced DNA lesions by O6-methylguanine-DNA methyltransferase (MGMT). However, some MGMT-deficient glioblastomas are still resistant to temozolomide, and the underlying molecular mechanisms remain unclear. We found that DYNC2H1 (DHC2) was expressed more in MGMT-deficient recurrent glioblastoma specimens and its expression strongly correlated to poor progression-free survival in MGMT promotor methylated glioblastoma patients. Furthermore, silencing DHC2, both in vitro and in vivo, enhanced temozolomide-induced DNA damage and significantly improved the efficiency of temozolomide treatment in MGMT-deficient glioblastoma. Using a combination of subcellular proteomics and in vitro analyses, we showed that DHC2 was involved in nuclear localization of the DNA repair proteins, namely XPC and CBX5, and knockdown of either XPC or CBX5 resulted in increased temozolomide-induced DNA damage. In summary, we identified the nuclear transportation of DNA repair proteins by DHC2 as a critical regulator of acquired temozolomide resistance in MGMT-deficient glioblastoma. Our study offers novel insights for improving therapeutic management of MGMT-deficient glioblastoma.

In recent years, the transsphenoidal approach has been extensively used surgically to treat parasellar, suprasellar, clival, and even petrous lesions. Extended pneumatization of the sphenoid sinus (SS) is considered an indispensable element for the extended transsphenoidal (ETS) approach. Because most anatomical studies of the ETS approach use Caucasian subjects, the present study aims to clarify the pneumatic extension types in Chinese individuals as well as any differences from those in Caucasians and analyze these differences with respect to the application of the ETS approach. A total of 200 computed tomography (CT) images of SSs and 18 adult cadaveric heads were selected for observation and measurement. The conchal, presellar, and sellar types comprised 6, 28.5, and 65.5% of subjects, respectively; according to the extra extension, the prevalence of the lateral, clival, lesser wing, and combined extension sinus types was 11.4, 21.4, 0.8, and 48.1% of subjects, respectively. The percentages of pneumatization of the anterior and posterior clinoid processes, pterygoid process, and optic strut were 5.0, 1.0, 22.3, and 7.0%, respectively. Onodi cells were observed in 61.1% of the sides of the cadaveric heads, including 30.6% with good pneumatization with identifiable optical or ICA bulges. These features were related to poor lateral and clival gasification in Chinese compared with Caucasians, which might make extended surgery more dangerous. However, the anterior pneumatization, especially the higher presentation of Onodi cells, ensures that the anterior ETS approach can be performed safely in Chinese patients. In general, measurements showing smaller sinus volumes and thicker bones with identifiable bone landmarks that are hard to find compared with those in Caucasians suggest increased surgical risks in the Chinese population. In this situation, carefully analysis of presurgical CT and magnetic resonance imaging scans is important. Furthermore, in the ETS approach, the use of stricter intraoperative technological devices such as neuronavigation and ultrasound Doppler is advisable.