Quantitative spectroscopic comparison of the optical properties of mouse cochlea microstructures using optical coherence tomography at 1.06†µm and 1.3†µm wavelengths.

Currently, the cochlear implantation procedure mainly relies on using a hand lens or surgical microscope, where the success rate and surgery time strongly depend on the surgeon's experience. Therefore, a real-time image guidance tool may facilitate the implantation procedure. In this study, we performed a systematic and quantitative analysis on the optical characterization of ex vivo mouse cochlear samples using two swept-source optical coherence tomography (OCT) systems operating at the 1.06-µm and 1.3-µm wavelengths. The analysis results demonstrated that the 1.06-µm OCT imaging system performed better than the 1.3-µm OCT imaging system in terms of the image contrast between the cochlear conduits and the neighboring cochlear bony wall structure. However, the 1.3-µm OCT imaging system allowed for greater imaging depth of the cochlear samples because of decreased tissue scattering. In addition, we have investigated the feasibility of identifying the electrode of the cochlear implant within the ex vivo cochlear sample with the 1.06-µm OCT imaging. The study results demonstrated the potential of developing an image guidance tool for the cochlea implantation procedure as well as other otorhinolaryngology applications.

Effect of A-scan rate and interscan interval on optical coherence angiography.

Optical coherence tomography angiography (OCTA) can provide rapid, volumetric, and noninvasive imaging of tissue microvasculature without the requirement of exogenous contrast agents. To investigate how A-scan rate and interscan time affected the contrast and dynamic range of OCTA, we developed a 1.06-µm swept-source OCT system enabling 100-kHz or 200-kHz OCT using two light sources. After system settings were carefully adjusted, almost the same detection sensitivity was achieved between the 100-kHz and 200-kHz modalities. OCTA of ear skin was performed on five mice. We used the variable interscan time analysis algorithm (VISTA) and the designated scanning protocol with OCTA images reconstructed through the correlation mapping method. With a relatively long interscan time (e.g., 12.5 ms vs. 6.25 ms for 200-kHz OCT), OCTA can identify more intricate microvascular networks. OCTA image sets with the same interscan time (e.g., 12.5 ms) were compared. OCTA images acquired with a 100-kHz A-scan rate showed finer microvasculature than did other imaging modalities. We performed quantitative analysis on the contrast from OCTA images reconstructed with different A-scan rates and interscan time intervals in terms of vessel area, total vessel length, and junction density.

A novel scoring system associating with preoperative platelet/lymphocyte and clinicopathologic features to predict lymph node metastasis in early gastric cancer.

BACKGROUND: Precise determination of the lymph node status is critical for determining appropriate treatment for early gastric cancer (EGC). This study attempted to establish a simple, effective risk scoring system to predict lymph node metastasis (LNM) in EGC by investigating the relationship between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and EGC LNM. MATERIALS AND METHODS: We retrospectively reviewed 312 operable patients with EGC. The clinical utility of PLR and NLR was tested by receiver operating characteristic curves. The scoring system was developed using independent risk factors. Finally, 89 EGC patients were collected from prospective database to validate the scoring system's accuracy. RESULTS: The optimal PLR and NLR cut-off values were 106 and 2.97, respectively. High NLR (P = 0.009) and PLR (P = 0.007) values were associated with LNM of EGC in univariate analyses, although only high PLR (P = 0.025) was an independent risk factor in multivariate analyses, together with age (P = 0.009), differentiation (P = 0.017), invasive depth (P < 0.001), and tumor size (P = 0.003). The scoring system's accuracy for retrospective and prospective data was 0.781 (95% confidence interval: 0.721-0.841) and 0.817 (95% confidence interval 0.714-0.920), respectively. CONCLUSIONS: Preoperative PLR and NLR correlate with EGC LNM. Our scoring system is reliable, accurate, and effective in predicting LNM in EGC patients.

Association between Genetic Polymorphisms in DEFB1 and Susceptibility to Digestive Diseases.

BACKGROUND: Aberrant expression of defensins is implicated in the pathogenesis of digestive diseases. However, the contribution of specific defensins and the influence of their genetic polymorphisms on the progression of digestive diseases remain controversial. In the present meta-analysis, we investigated the association between DEFB1 SNPs and the susceptibility to digestive diseases. MATERIAL AND METHODS: Case-control studies that reported the correlation between DEFB1 SNPs and the susceptibility to digestive diseases were identified through electronic databases searches, and high-quality studies that satisfied our inclusion criteria were selected for this meta-analysis. Statistical analyses were performed utilizing STATA software version 12.0. RESULTS: The present meta-analysis revealed that patients with digestive diseases exhibited higher frequencies of the DEFB1 genetic variants rs11362G>A, rs1800972C>G, and rs1799946G>A compared to healthy controls under the allele model. Subgroup analysis based on country showed that the rs1800972C>G variant under allele model and rs1799946G>A are associated with the susceptibility to digestive diseases in Hungarian and Italian populations, respectively. Subgroup analysis based on disease type showed that: (1) rs11362G>A variant was strongly associated with severe acute pancreatitis (SAP) and chronic gastritis, (2) frequency of rs1800972C>G variant was higher in SAP subgroup, and (3) frequency of rs1799946G>A variant was positively associated with the susceptibility to Crohn's disease (CD) under the allele model and with SAP. CONCLUSIONS: Our meta-analysis provides evidence that DEFB1 genetic polymorphisms rs11362G>A, rs1800972C>G and rs1799946G>A are important contributing factors to the development of digestive diseases.

Correlations of common polymorphism of EVI-1 gene targeted by miRNA-206/133b with the pathogenesis of breast cancer.

The aim of this study was to identify the correlations of a common polymorphism (rs6774494 A > G) in the EVI-1 gene targeted by micro-RNA (miRNA)-206/133b with the pathogenesis of breast cancer (BC). A total of 196 unrelated ethnic Han Chinese women diagnosed with primary BC were consecutively recruited and 200 healthy controls were randomly selected from the same population-based cohort. Direct PCR sequencing assay was used to detection of rs6774494 A > G polymorphism in the EVI-1 gene. Real-time quantitative PCR (RT-PCR) analysis was performed to verify the alterations of the EVI1 messenger RNA (mRNA) levels. Kaplan-Meier analysis was used to investigate and to estimate the survival outcomes for each endpoint. All statistical analyses were performed with SPSS software (version 18.0, SPSS, Chicago, IL). Our results demonstrated that the carriers of EVI-1 AG genotype were more likely to develop BC when compared with the EVI-1 GG genotype (P = 0.034, OR = 1.26, 95% CI = 1.02 ∼ 1.57). In addition, it was found that patients with the G (AG + GG) allele of EVI-1 genetic variants were associated with higher risk of BC compared with the EVI-1 AA genotype (OR = 1.26, 95% CI = 1.02 ∼ 1.54, P = 0.028). The results of a subgroup analysis stratified by menopause revealed that in female post-menopause subgroup patients with the EVI-1 G allele were correlated with a higher risk of BC than those with the EVI-1 AA genotype (OR = 1.31, 95% CI = 1.00 ∼ 1.72, P = 0.054). Kaplan-Meier analyses suggested that carriers of the G allele (AG + GG) were associated with poorer overall survival (OS) and progression-free survival (PFS) compared with those with AA genotype (OS P = 0.042; PFS P = 0.036, respectively). The correlation analysis showed that EVI-1 mRNA levels were negatively associated with miRNA-206/133b levels in the carriers of the G allele (AG + GG) (r = -1.274, P < 0.05). Our findings provide evidence that the EVI-1 rs6774494 G > A polymorphism targeted by miRNA-206/133b may contribute to the pathogenesis of BC.

Influence of DPYD Genetic Polymorphisms on 5-Fluorouracil Toxicities in Patients with Colorectal Cancer: A Meta-Analysis.

Our meta-analysis aggregated existing results from relevant studies to comprehensively investigate the correlations between genetic polymorphisms in dihydropyrimidine dehydrogenase (DPYD) gene and 5-fluorouracil (5-FU) toxicities in patients with colorectal cancer (CRC). The MEDLINE (1966∼2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980∼2013), CINAHL (1982∼2013), Web of Science (1945∼2013), and the Chinese Biomedical Database (CBM) (1982∼2013) were searched without language restrictions. Meta-analyses were conducted with the use of STATA software (Version 12.0, Stata Corporation, College Station, TX, USA). Seven clinical cohort studies with a total of 946 CRC patients met our inclusion criteria, and NOS scores of each of the included studies were ≥5. Our findings showed that DPYD genetic polymorphisms were significantly correlated with high incidences of 5-FU-related toxicity in CRC patients. SNP-stratified analysis indicated that there were remarkable connections of IVS14+1G>A, 464T>A, and 2194G>A polymorphisms with the incidence of marrow suppression in CRC patients receiving 5-FU chemotherapy. Furthermore, we found that IVS14+1G>A, 496A>G, and 2194G>A polymorphisms were correlated with the incidence of gastrointestinal reaction. Ethnicity-stratified analysis also revealed that DPYD genetic polymorphisms might contribute to the development of marrow suppression and gastrointestinal reaction among Asians, but not among Caucasians. The present meta-analysis suggests that DPYD genetic polymorphisms may be correlated with the incidence of 5-FU-related toxicity in CRC patients.

Glycyrrhetinic acid exhibits strong inhibitory effects towards UDP-glucuronosyltransferase (UGT) 1A3 and 2B7.

The aim of the present study is to evaluate the inhibitory effects of liver UDP-glucuronosyltransferases (UGTs) by glycyrrhizic acid and glycyrrhetinic acid, which are the bioactive ingredients isolated from licorice. The results showed that glycyrrhetinic acid exhibited stronger inhibition towards all the tested UGT isoforms, indicating that the deglycosylation process played an important role in the inhibitory potential towards UGT isoforms. Furthermore, the inhibition kinetic type and parameters were determined for the inhibition of glycyrrhetinic acid towards UGT1A3 and UGT2B7. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that the inhibition of UGT1A3 and UGT2B7 by glycyrrhetinic acid was best fit to competitive and noncompetitive type, respectively. The second plot using the slopes from Lineweaver-Burk plots versus glycyrrhetinic acid concentrations was employed to calculate the inhibition kinetic parameters (K(i)), and the values were calculated to be 0.2 and 1.7 µM for UGT1A3 and UGT2B7, respectively. All these results remind us the possibility of UGT inhibition-based herb-drug interaction. However, the explanation of these in vitro parameters should be paid more caution due to complicated factors, including the probe substrate-dependent UGT inhibition behaviour, environmental factors affecting the abundance of herbs' ingredients, and individual difference of pharmacokinetic factors.