Objective evaluation of tongue diagnosis ability using a tongue diagnosis e-learning/e-assessment system based on a standardized tongue image database.

Background: In Kampo medicine, tongue examination is used to diagnose the pathological condition "Sho," but an objective evaluation method for its diagnostic ability has not been established. We constructed a tongue diagnosis electronic learning and evaluation system based on a standardized tongue image database. Purpose: This study aims to verify the practicality of this assessment system by evaluating the tongue diagnosis ability of Kampo specialists (KSs), medical professionals, and students. Methods: In the first study, we analyzed the answer data of 15 KSs in an 80-question tongue diagnosis test that assesses eight aspects of tongue findings and evaluated the (i) test score, (ii) test difficulty and discrimination index, (iii) diagnostic consistency, and (iv) diagnostic match rate between KSs. In the second study, we administered a 20-question common Kampo test and analyzed the answer data of 107 medical professionals and 56 students that assessed the tongue color discrimination ability and evaluated the (v) correct answer rate, (vi) test difficulty, and (vii) factors related to the correct answer rate. Result: In the first study, the average test score was 62.2 ± 10.7 points. Twenty-eight questions were difficult (correct answer rate, <50%), 34 were moderate (50%-85%), and 18 were easy (≥85%). Regarding intrarater reliability, the average diagnostic match rate of five KSs involved in database construction was 0.66 ± 0.08, and as for interrater reliability, the diagnostic match rate between the 15 KSs was 0.52 (95% confidence interval, 0.38-0.65) for Gwet's agreement coefficient 1, and the degree of the match rate was moderate. In the second study, the difficulty level of questions was moderate, with a correct rate of 81.3% for medical professionals and 82.1% for students. The discrimination index was good for medical professionals (0.35) and poor for students (0.06). Among medical professionals, the correct answer group of this question had a significantly higher total score on the Kampo common test than the incorrect answer group (85.3 ± 8.4 points vs. 75.8 ± 11.8 points, p < 0.01). Conclusion: This system can objectively evaluate tongue diagnosis ability and has high practicality. Utilizing this system can be expected to contribute to improving learners' tongue diagnosis ability and standardization of tongue diagnosis.

Construction of a Standardized Tongue Image Database for Diagnostic Education: Development of a Tongue Diagnosis e-Learning System.

Tongue examination is an important diagnostic method for judging pathological conditions in Kampo (traditional Japanese medicine), but it is not easy for beginners to learn the diagnostic technique. One reason is that there are few objective diagnostic criteria for tongue examination findings, and the educational method for tongue examination is not standardized in Japan, warranting the need for a tongue image database for e-learning systems that could dramatically improve the efficiency of education. Therefore, we constructed a database comprising tongue images whose findings were determined on the basis of votes given by five Kampo medicine specialists (KMSs) and confirmed the educational usefulness of the database for tongue diagnosis e-learning systems. The study was conducted in the following five steps: development of a tongue imaging collection system, collection of tongue images, evaluation and annotation of tongue images, development of a tongue diagnosis e-learning system, and verification of the educational usefulness of this system. Five KMSs evaluated the tongue images obtained from 125 participants in the following eight aspects: (i) tongue body size, (ii) tongue body color, (iii) tongue body dryness and wetness, (iv) tooth marks on the edge of the tongue, (v) cracks on the surface of the tongue, (vi) thickness of tongue coating, (vii) color of tongue coating, and (viii) dryness and wetness of tongue coating. Medical students (MSs) were given a tongue diagnosis test using an e-learning system after a lecture on tongue diagnosis. The cumulative and individual match rates (%) (individual match rates of 100% (5/5), 80% (4/5), and 60% (3/5) are shown in parentheses, respectively) were as follows: (i) tongue body size: 92.8 (26.4/26.4/40.0); (ii) tongue body color: 83.2 (10.4/20.8/52.0); (iii) tongue body dryness and wetness: 88.8 (13.6/34.4/40.8); (iv) tooth marks on the edge of the tongue: 88.8 (6.4/35.2/47.2); (v) cracks on the surface of the tongue: 96.8 (24.0/35.2/37.6); (vi) thickness of tongue coating: 84.8 (7.2/21.6/56.0); (vii) color of tongue coating: 88.0 (15.2/37.6/35.2); and (viii) dryness and wetness of tongue coating: 74.4 (4.8/19.2/50.4). The test showed that the tongue diagnosis ability of MSs who attended a lecture on tongue diagnosis was almost the same as that of KMSs. We successfully constructed a tongue image database standardized for training specialists on tongue diagnosis and confirmed the educational usefulness of the e-learning system using a database. This database will contribute to the standardization and popularization of Kampo education.

A new prognostic model for hepatocellular carcinoma recurrence after curative hepatectomy.

We previously reported the effectiveness of the product of tumor number and size (NxS factor) for the prognosis of hepatocellular carcinoma (HCC) in patients following hepatectomy. The present study aimed to propose a new score based on the NxS factor to predict HCC recurrence following hepatectomy. A total of 406 patients who underwent hepatectomy for HCC at Osaka University Graduate School of Medicine were retrospectively analyzed to develop the new score. Among clinicopathological factors, including the NxS factor, the marker subset that achieved the best performance for prediction of early recurrence was assessed, and a prognostic model for HCC recurrence after curative hepatectomy (REACH) was developed. As the validation set, 425 patients who underwent hepatectomy for HCC at Yamaguchi University Graduate School of Medicine and Shimonoseki Medical Center were analyzed, and the prognostic ability of the REACH score was compared with that of well-known staging systems. Following analysis, the REACH score was constructed using six covariates (NxS factor, microscopic hepatic vein invasion, differentiation, serum albumin, platelet count and indocyanine green retention rate at 15 min). In the validation set, the REACH score predicted early recurrence in 73 of 81 samples, with a sensitivity of 89% and a specificity of 58%. The area under the curve (AUC) of the receiver operating characteristic curve of the REACH score was 0.78 and 0.74, respectively, for 1- and 2-year recurrence after hepatectomy; each AUC was higher than that of any of the other staging systems. Survival analysis indicated the REACH score had the best predictive value in disease-free and overall survival. The present findings demonstrated that the REACH score may be used to classify patients with HCC into high- and low-risk of recurrence, and to predict subsequent survival following hepatic resection.

Expression levels of UL16 binding protein 1 and natural killer group 2 member D affect overall survival in patients with gastric cancer following gastrectomy.

UL16 binding protein 1 (ULBP1) expressed on the tumor cell surface binds to the natural killer group 2 member D (NKG2D) receptor presenting on natural killer (NK), cluster of differentiation (CD)8+ T, and γ δ T cells. However, the roles of ULBP1 and NKG2D expression and associated immune responses in gastric cancer are unclear. The present study investigated the associations between ULBP1 and NKG2D expression and clinical outcomes in patients with gastric cancer. The levels of ULBP1 and NKG2D expression were examined in human gastric cancer cell lines and gastric cancer tissues from 98 patients who underwent surgery from 2004 to 2008. MKN-74 cells expressed ULBP1 with ULBP2, -5, or -6. NKG2D was expressed at a higher level following activation of T cells and NK cells. Among the tissue sections positive for NKG2D expression, 6 patients were positive for CD8 and CD56. In all tissues, NKG2D-expressing cells were typically aCD8+ T cells. Patients with NKG2D expression in tumors exhibited significantly longer overall survival (OS) compared with patients without NKG2D expression in tumors (P=0.0217). The longest OS was observed in patients positive for ULBP1 and NKG2D, whereas the shortest OS was observed in patients negative for ULBP1 and NKG2D. The interaction between ULBP1 and NKG2D may improve OS in patients with gastric cancer, and may have applications in immunotherapy for the induction of adaptive immunity in patients with cancer. Additionally, ULBP1 and NKG2D may be useful as prognostic biomarkers in gastric cancer.

Prediction of Early Recurrence of Liver Cancer by a Novel Discrete Bayes Decision Rule for Personalized Medicine.

We discuss a novel diagnostic method for predicting the early recurrence of liver cancer with high accuracy for personalized medicine. The difficulty with cancer treatment is that even if the types of cancer are the same, the cancers vary depending on the patient. Thus, remarkable attention has been paid to personalized medicine. Unfortunately, although the Tokyo Score, the Modified JIS, and the TNM classification have been proposed as liver scoring systems, none of these scoring systems have met the needs of clinical practice. In this paper, we convert continuous and discrete data to categorical data and keep the natively categorical data as is. Then, we propose a discrete Bayes decision rule that can deal with the categorical data. This may lead to its use with various types of laboratory data. Experimental results show that the proposed method produced a sensitivity of 0.86 and a specificity of 0.49 for the test samples. This suggests that our method may be superior to the well-known Tokyo Score, the Modified JIS, and the TNM classification in terms of sensitivity. Additional comparative study shows that if the numbers of test samples in two classes are the same, this method works well in terms of the F1 measure compared to the existing scoring methods.

Web-Based Evaluation System to Measure Learning Effectiveness in Kampo Medicine.

Measuring the learning effectiveness of Kampo Medicine (KM) education is challenging. The aim of this study was to develop a web-based test to measure the learning effectiveness of KM education among medical students (MSs). We used an open-source Moodle platform to test 30 multiple-choice questions classified into 8-type fields (eight basic concepts of KM) including "qi-blood-fluid" and "five-element" theories, on 117 fourth-year MSs. The mean (±standard deviation [SD]) score on the web-based test was 30.2 ± 11.9 (/100). The correct answer rate ranged from 17% to 36%. A pattern-based portfolio enabled these rates to be individualized in terms of KM proficiency. MSs with scores higher (n = 19) or lower (n = 14) than mean ± 1SD were defined as high or low achievers, respectively. Cluster analysis using the correct answer rates for the 8-type field questions revealed clear divisions between high and low achievers. Interestingly, each high achiever had a different proficiency pattern. In contrast, three major clusters were evident among low achievers, all of whom responded with a low percentage of or no correct answers. In addition, a combination of three questions accurately classified high and low achievers. These findings suggest that our web-based test allows individual quantitative assessment of the learning effectiveness of KM education among MSs.

Constipation and herbal medicine.

Constipation is characterized by a variety of bowel symptoms such as difficulty passing stool, hard stool, and a feeling of incomplete evacuation. The multifactorial causes of constipation limit the clinical efficacy of current conventional treatments that use a single drug that acts through only one pathway. To complement the shortcomings of the current Western medical model and provide a complete holistic approach, herbal medicines capable of targeting multiple organs and cellular sites may be used. In Japan, many herbs and herbal combinations have traditionally been used as foods and medicines. Currently, Japanese physicians use standardized herbal combinations that provide consistent and essential quality and quantity. This review highlights representative Japanese herbal medicines (JHMs), Rhei rhizoma-based JHMs including Daiokanzoto and Mashiningan, and Kenchuto-based JHMs including Keishikashakuyakuto and Daikenchuto, which coordinate the motility of the alimentary tract. This review provides a framework to better understand the clinical and pharmacological efficacies of JHMs on constipation according to the unique theory of Japanese traditional medicine, known as Kampo medicine.

Preoperative serum methylation signature as prognostic tool after curative hepatectomy in patients with hepatocellular carcinoma.

AIM: This study aimed to investigate the relationship between prognosis after curative hepatectomy and serum methylation signature (SMS), defined by methylation levels of six specific genes (cyclin D2, Ras association (RalGDS/AF-6) domain family member 1, serine peptidase inhibitor Kunitz type 2, cystic fibrosis transmembrane conductance regulator, brain abundant membrane attached signal protein 1, and steroid-5-alpha-reductase alpha polypeptide 2). PATIENTS AND METHODS: Serum samples were collected preoperatively from 125 patients with hepatocellular carcinoma associated with hepatitis C virus infection who underwent curative hepatectomy. We measured the methylation levels of the preceding six genes. We defined the methylation of three genes or more in the serum as SMS-positive in this study. We investigated the prognosis of SMS-positive patients. RESULTS: SMS-positive patients exhibited significantly shorter disease-free survival (DFS) and overall survival (OS) than SMS-negative patients (p=0.0002 and p<0.0001, respectively). Multivariate analysis showed that SMS positivity was an independent risk factor for shorter DFS (hazard ratio (HR)=2.182; p<0.001) and OS (HR=4.198; p<0.001). CONCLUSION: SMS is useful as a prognostic predictor in patients with hepatocellular carcinoma after curative hepatectomy.

An accurate prognostic staging system for hepatocellular carcinoma patients after curative hepatectomy.

The aim of this study was to develop an accurate predictive system for prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy. We pooled data of clinicopathological features of 234 HCC patients who underwent curative hepatectomy. On the basis of the pooled data, we established a simple predictive staging system (PS score) scored by the mathematical product of tumor number and size, and degree of liver function. We compared the prognostic abilities of the PS score (score 0-3) with those of six well-known clinical staging systems. Then, we found that there were significant differences (P<0.05) in both disease-free survival (DFS) and overall survival (OS) between patients with different PS scores (PS score 0 vs. 1; PS score 1 vs. 2), and there was a significant difference in DFS, but not OS, between patients with PS score 2 and those with PS score 3. Moreover, the PS score had smaller values of the Akaike information criterion for both DFS and OS than any of the six well-known clinical staging systems. These results suggest that the PS score serves as a simple, accurate predictor for the prognosis of HCC patients after hepatectomy.

Predictive biomarkers for the outcome of vaccination of five therapeutic epitope peptides for colorectal cancer.

BACKGROUND: We previously reported a phase I study of a cancer vaccine using five novel HLA-A*2402-restricted peptides, and demonstrated the safety and the promising potential of our five-peptide cocktail for advanced colorectal cancer. The objective of this analysis was to investigate predictive biomarkers for the prior selection of patients who are likely to have clinical benefit from such therapy. PATIENTS AND METHODS: Seventeen patients with colorectal cancer who were treated with the five peptides underwent a complete blood count, serum chemistry tests and enzyme-linked ImmunoSpot assay before the treatment as predictive markers of high reactivity to the peptides. RESULTS: Interleukin-6 level was a significant predictor for overall survival of patients treated with the peptide cocktail (p=0.017). A high neutrophil/lymphocyte ratio was likely to have some association with the poor induction of peptide-specific immune reaction. CONCLUSION: Interleukin-6 level might be a good predictive biomarker for clinical benefit of patients treated with this peptide vaccine.

A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model.

A therapeutic vaccine against minimal residual cancer cells is needed for the treatment of patients with colorectal cancer. Several gene therapy studies have revealed that the combination of a suicide gene and cytokine gene might induce effective antitumor immunity. In this study, we constructed an interleukin (IL)-18 and herpes simplex virus-thymidine kinase (HSV-TK) expression vector driven by the human telomerase reverse transcriptase (hTERT) promoter to study the efficacy of combination gene therapy with IL-18 and the HSV-TK suicide gene. Low immunogenic colon 26 cells were used for transfection and inoculation into syngeneic BALB/c mice. Large established tumors of colon 26 transfectants expressing IL-18 and HSV-TK driven by the hTERT promoter were completely eradicated after GCV administration in syngeneic BALB/c mice. Immunohistochemical analysis at the tumor rejection sites revealed enormous infiltrations of CD8+ T lymphocytes as well as CD4+ T lymphocytes and CD11b+ monocytes. Moreover, established distant tumors were completely eradicated by vaccination with the IL-18 and HSV-TK transfectants in combination with GCV. These data suggest that the IL-18 and suicide gene therapy can elicit antitumor specific immunity. In conclusion, gene therapy with IL-18 and HSV-TK plasmid vector driven by the hTERT promoter may be useful for cancer vaccination.

A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome.

BACKGROUND: To evaluate the safety of combination vaccine treatment of multiple peptides, phase I clinical trial was conducted for patients with advanced colorectal cancer using five novel HLA-A*2402-restricted peptides, three peptides derived from oncoantigens, ring finger protein 43 (RNF43), 34 kDa-translocase of the outer mitochondrial membrane (TOMM34), and insulin-like growth factor-II mRNA binding protein 3 (KOC1), and the remaining two from angiogenesis factors, vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2. METHODS: Eighteen HLA- A*2402-positive colorectal cancer patients who had failed to standard therapy were enrolled in this study. 0.5 mg, 1.0 mg or 3.0 mg each of the peptides was mixed with incomplete Freund's adjuvant and then subcutaneously injected at five separated sites once a week. We also examined possible effect of a single site injection of "the cocktail of 5 peptides" on the immunological responses. ELISPOT assay was performed before and after vaccinations in the schedule of every 4 weeks. RESULTS: The vaccine treatment using multiple peptides was well tolerated without any severe treatment-associated systemic adverse events. Dose-dependent induction of peptide-specific cytotoxic T lymphocytes was observed. The single injection of "peptides cocktail" did not diminish the immunological responses. Regarding the clinical outcome, one patient achieved complete response and 6 patients revealed stable disease for 4 to 7 months. The median overall survival time (MST) was 13.5 months. Patients, in which we detected induction of cytotoxic T lymphocytes specific to 3 or more peptides, revealed significantly better prognosis (MST; 27.8 months) than those with poorer immune responses (MST; 3.7 months) (p = 0.032). CONCLUSION: Our cancer vaccine treatment using multiple peptides is a promising approach for advanced colorectal cancer with the minimum risk of systemic adverse reactions. CLINICAL TRIAL REGISTRATION: UMIN-CTR number UMIN000004948.

ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma.

The poor prognosis of hepatocellular carcinoma (HCC) can be explained largely by the high rate of intrahepatic recurrence (IHR). Identification of genes related to IHR is needed to improve the poor prognosis and important for personalized medicine. Eighty-one HCC specimens were used in this study. We screened for IHR-related genes by DNA microarray analysis. The validation of screening was performed by using real-time PCR. The methylation levels in genomic DNAs were measured by quantitative methylation-specific PCR. Six hepatoma cell lines were used for examination of ABCB6 expressional regulation. Time-to-event analyses for recurrence after surgery were analyzed by Kaplan-Meier analysis and Cox regression analysis with cutoff values obtained from receiver operating characteristic (ROC) analysis. We confirmed that ABCB6 mRNA levels were significantly higher in hepatitis C virus (HCV)-related HCCs with early IHR compared to HCV-related HCCs without early IHR (2.5-fold, P=0.01) and the corresponding non-cancerous livers (3.1-fold, P=0.05). Experiments with cell lines showed correlation between DNA methylation and mRNA levels of ABCB6. ROC analysis revealed that mRNA levels (0.81 area under the curve, 88% sensitivity and 72% specificity) and DNA methylation levels (0.81 area under the curve, 80% sensitivity and 80% specificity) of ABCB6 in HCV-related HCCs allowed for the accurate discrimination of the development of early IHR. Cox regression analysis revealed that ABCB6 mRNA levels was an independent risk factor for IHR of HCV-related HCC. Aberrant mRNA and DNA methylation levels of ABCB6 may serve as useful predictive biomarkers for early IHR of HCV-related HCC.

Susceptibility of hepatoma-derived cells to histone deacetylase inhibitors is associated with ID2 expression.

Downregulation of inhibitor of DNA binding 2 (ID2) is associated with poor prognosis in cases of hepatocellular carcinoma (HCC). Therefore, to search for effective antitumor drugs for the treatment of HCC exhibiting poor prognostic indicators, we used two HCC-derived cell lines (HuH-7 and HLE) to alter ID2 levels. Specifically, ID2 expression was knocked down in HuH-7 cells via transfection with ID2-specific small interfering RNAs and separately ID2 was overexpressed in HLE cells via an ID2 expression plasmid vector. To assess the effect of antitumor drugs, MTS assay was performed. Annexin V staining was used to evaluate apoptosis and real-time RT-PCR was used to measure mRNA levels. ID2 knockdown cells were more susceptible to histone deacethylase (HDAC) inhibitors including sodium butyrate (NaB), sodium 4-phenyl-butyrate, tricostatin A, suberoylanilide hydroxamic acid, MS-275, apicidin and HC-toxin. Conversely, cells that overexpressed ID2 were less susceptible than control cells to HDAC inhibitors. NaB-induced apoptosis was inversely correlated with ID2 expression. Expression of the anti-apoptotic mRNA BCL2 was induced by NaB in control cells, but this induction of BCL2 was inhibited by ID2 knockdown and strengthened by ID2 overexpression. Expression of another anti-apoptotic mRNA, BCL2L1, was decreased by NaB administration and then partially recovered. However, in ID2 knockdown cells, BCL2L1 levels did not recover from NaB-induced suppression. ID2 affected the susceptibility of two HCC-derived cell lines to an HDAC inhibitor by regulating the expression of anti-apoptotic genes. Therefore, HDAC inhibitors may be effective for the treatment of HCC for which the prognosis is poor based on ID2 downregulation and ID2 could serve as a marker that is predictive of the clinical response to HDAC inhibitors.

Photon pair generation in a silicon micro-ring resonator with reverse bias enhancement.

Photon sources are fundamental components for any quantum photonic technology. The ability to generate high count-rate and low-noise correlated photon pairs via spontaneous parametric down-conversion using bulk crystals has been the cornerstone of modern quantum optics. However, future practical quantum technologies will require a scalable integration approach, and waveguide-based photon sources with high-count rate and low-noise characteristics will be an essential part of chip-based quantum technologies. Here, we demonstrate photon pair generation through spontaneous four-wave mixing in a silicon micro-ring resonator, reporting separately a maximum coincidence-to-accidental (CAR) ratio of 602 ± 37 (for a generation rate of 827kHz), and a maximum photon pair generation rate of 123 MHz ± 11 kHz (with a CAR value of 37). To overcome free-carrier related performance degradations we have investigated reverse biased p-i-n structures, demonstrating an improvement in the pair generation rate by a factor of up to 2 with negligible impact on CAR.

Proteomic differential display identifies upregulated vinculin as a possible biomarker of pancreatic cancer.

Pancreatic cancer (PC) is characterized by rapid tumor spread, and very few patients with PC survive for more than 5 years. It is imperative to discover additional diagnostic biomarkers or specific therapeutic targets in order to improve the treatment of patients with PC. In search for useful biomarkers, we analyzed ten pairs of non-cancerous and cancer tissues from patients with PC by two-dimensional gel electrophoresis (2-DE). Nineteen protein spots showed differential expression on 2-DE gels between the cancer and non-cancerous tissues. Six upregulated protein spots were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as calreticulin, glutathione synthetase, stathmin, vinculin, α-enolase and glyceraldehyde-3-phosphate dehydrogenase. Western blotting demonstrated that vinculin was predominantly expressed in the pancreatic cancer tissues compared with to non-cancerous tissues. Our findings indicate that vinculin may be a clinically useful biomarker of PC.

Glyoxalase I (GLO1) is up-regulated in pancreatic cancerous tissues compared with related non-cancerous tissues.

BACKGROUND: Glyoxalase I (GLO1), an enzyme involved in the detoxification of methylglyoxal in the glycolysis pathway, has been found to be frequently overexpressed in various types of cancer. Recent studies showed that GLO1 is related to proliferation and apoptosis in human cancer cells. However, expression of GLO1 in pancreatic cancer (PC) has not been precisely defined. Since PC is one of the most malignant types of cancer, we investigated the levels of GLO1 in tissues from patients with PC. MATERIALS AND METHODS: We examined the expression of GLO1 in tumors from patients with PC and adjacent normal tissues by western blotting. RESULTS: Western blotting demonstrated that GLO1 was significantly overexpressed in pancreatic cancerous tissues compared with adjacent non-cancerous tissues (n=20, p<0.05). CONCLUSION: GLO1 could be a clinically useful target in the therapy of PC.

Overexpression of the RD RNA binding protein in hepatitis C virus-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) often exhibits a poor prognosis due to metastatic spread caused by portal vein invasion (PVI). In the present study, we attempted to identify a novel therapeutic target related to PVI of HCC. Based on pooled genomic data, we identified RD RNA binding protein (RDBP), a member of the negative elongation factor (NELF) transcription elongation regulatory complex, to be preferentially overexpressed in HCC with PVI. We used quantitative reverse transcription polymerase chain reaction (RT-PCR) and immuno-histochemical analyses to investigate the relationship between RDBP mRNA and protein with metastatic potential in sample sets of hepatitis C virus (HCV)-related HCC and corresponding non-HCC liver tissues. We also used the small interfering RNA technique to examine the role of RDBP in invasion and proliferation of HCC cells in vitro. Our data showed that both mRNA and protein levels of RDBP were significantly higher in HCC compared to non-HCC liver tissue, and that these levels were also significantly higher in HCC with PVI compared to HCC without PVI. Multivariate analysis revealed that RDBP protein levels were an independent risk factor for early intrahepatic recurrence of HCC within 2 years of surgery. Knockdown of RDBP protein significantly inhibited the proliferation and invasion of cells in vitro. These data demonstrate that RDBP is related to the metastatic potential of HCC, suggesting a possible candidate for prevention of HCC cell metastasis.

Inter-rater reliability of self-reported response on foreskin status in questionnaire among Japanese adult men.

OBJECTIVES: To determine whether foreskin status is a measurable marker for evaluating the effect of the foreskin on sexually transmitted infections. METHODS: Inter-rater comparison of the responses on foreskin status and circumcision in a self-report questionnaire with the findings of a physical examination by an experienced well-trained urologist was performed for patients who visited a healthcare facility in Kanagawa, Japan. Foreskin status was defined using a five-point graphical scale based on the degree to which the foreskin covers the foreskin and the glans penis in a non-erectile condition: type 1, a fully exposed glans penis; types 2-4, the glans penis partly covered by the foreskin and type 5, phimosis. Linear weighted κ and per cent agreement were used to evaluate the reliability of responses. RESULTS: Among 188 participants who were evaluated about their foreskin status, linear weighted κ and per cent agreement were 0.74% and 68.4%, respectively. Linear weighted κ improved from 0.74 to 0.80 when the number of categories was changed to three. All the self-reported responses on circumcision were in agreement with the findings of the physical examination. Seventeen participants (9.0%) had been circumcised, and among them, three (17.6%) had approximately one-half of their glans penis covered by the foreskin. In 90 among the 171 uncircumcised participants (52.6%), the foreskin did not cover the glans penis. CONCLUSIONS: The self-reported response on foreskin status in this questionnaire has sufficient reliability to replace physical examination, and this questionnaire can facilitate further studies about the effect of foreskin on sexually transmitted infections.