Significance of Hypermethylation of Tumor-Suppressor Genes PTGER4 and ZNF43 at CpG Sites in the Prognosis of Colorectal Cancer.

The status of DNA methylation in primary tumor tissue and adjacent tumor-free tissue is associated with the occurrence of aggressive colorectal cancer (CRC) and can aid personalized cancer treatments at early stages. Tumor tissue and matched adjacent nontumorous tissue were extracted from 208 patients with CRC, and the correlation between the methylation levels of PTGER4 and ZNF43 at certain CpG loci and the prognostic factors of CRC was determined using the MassARRAY System testing platform. The Wilcoxon signed-rank test, a Chi-square test, and McNemar's test were used for group comparisons, and Kaplan-Meier curves and a log-rank test were used for prediction. The hypermethylation of PTGER4 at the CpG_4, CpG_5, CpG_15, and CpG_17 tumor tissue sites was strongly correlated with shorter recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) [hazard ratio (HR) = 3.26, 95% confidence interval (CI) = 1.38-7.73 for RFS, HR = 2.35 and 95% CI = 1.17-4.71 for PFS, HR = 4.32 and 95% CI = 1.8-10.5 for OS]. By contrast, RFS and PFS were significantly longer in the case of increased methylation of ZNF43 at the CpG_5 site of normal tissue [HR = 2.33, 95% CI = 1.07-5.08 for RFS, HR = 2.42 and 95% CI = 1.19-4.91 for PFS]. Aberrant methylation at specific CpG sites indicates tissue with aggressive behavior. Therefore, the differential methylation of PTGER4 and ZNF43 at specific loci can be employed for the prognosis of patients with CRC.

Human Papillomavirus and Risk of Colorectal Cancer: An Analysis of Nationwide Claims Data.

Background and Objectives: Although human papillomavirus (HPV) is a major etiology of cervical and anogenital cancers, whether it is associated with colorectal carcinogenesis is yet undetermined. Materials and Methods: The longitudinal association of HPV infection with colorectal cancer (CRC) was evaluated using 2000-2013 data from a nationwide Taiwanese claims database. In this retrospective cohort study, 358 patients with primary HPV diagnoses (HPV-infected cohort) and 1432 patients without such a diagnosis (HPV-uninfected cohort) were recruited between 2000 and 2006. Both cohorts were followed up to identify CRC incidences from 2006 to 2013. Hazard ratios (HRs) and their 95% confidence intervals (CIs) derived from Cox proportional hazards models were used to estimate the association between HPV and CRC risk. Results: The HPV-infected cohort had a significantly higher cumulative incidence of CRC than the HPV-uninfected cohort. The presence of HPV was associated with an increased risk of CRC (adjusted HR, 1.63; 95% CI, 1.02-3.62). Furthermore, the significant HPV-CRC risk association was evident in both sexes. Conclusions: This population-based cohort study reveals longitudinal evidence that HPV is associated with an increased risk of CRC. Further studies are required to verify the role of HPV in colorectal carcinogenesis.

Association between gastroesophageal reflux disease and colorectal cancer risk: a population-based cohort study.

PURPOSE: Several studies have investigated the association between gastroesophageal reflux disease (GERD) and colorectal cancer (CRC) risk, but the presented scientific results are highly debatable. This study examined the longitudinal association between GERD and CRC in an Asian population. METHODS: A retrospective cohort study was performed using the National Health Insurance Research Database of Taiwan. The study cohort comprised 45,828 individuals with newly diagnosed GERD (the GERD cohort) and 229,140 age, sex, and date of enrollment-matched patients without GERD (the comparison cohort) from 2000 to 2006. The primary outcome was the incidence of CRC. To estimate the effect of GERD on the risk of CRC, the Cox proportional hazards model was fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: There were 785 newly diagnosed CRC patients in the 45,828 patients with GERD. Relatively, there were 2375 incident CRC cases in 229,140 patients without GERD. The incidence rate of CRC for the GERD cohort (17.60 per 10,000 person-years) was significantly higher than the corresponding incidence rate for the comparison cohort (10.22 per 10,000 person-years). After adjustment for confounders, GERD was associated with a significantly increased risk of CRC (adjusted HR,1.76; 95% CI, 1.62-2.90). Of note, a significant association between GERD and CRC risk was evident in both genders. CONCLUSIONS: In conclusion, this nationwide population-based cohort study supports the hypothesis that GERD was associated with a significantly increased risk of CRC. Our findings warrant still further investigation of the underlying mechanisms related to carcinogenic effect of GERD on colorectal carcinoma.

A Novel Prognostic DNA Methylation Panel for Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers and the second leading cause of cancer-related deaths. Discrepancies in clinical outcomes are observed even among patients with same-stage CRC due to molecular heterogeneity. Thus, biomarkers for predicting prognosis in CRC patients are urgently needed. We previously demonstrated that stage II CRC patients with NKX6.1 methylation had poor 5-year overall survival. However, the methylation frequency of NKX6.1 was only 23% in 151 pairs of CRC tissues. Thus, we aimed to develop a more robust prognostic panel for CRC using NKX6.1 in combination with three genes: LIM homeobox transcription factor 1α (LMX1A), sex-determining region Y-box 1 (SOX1), and zinc finger protein 177 (ZNF177). Through quantitative methylation analysis, we found that LMX1A, SOX1, and ZNF177 were hypermethylated in CRC tissues. LMX1A methylation was significantly associated with poor 5-year overall, and disease-free survivals in stage I and II CRC patients. Sensitivity and specificity analyses of the four-gene combination revealed the best sensitivity and optimal specificity. Moreover, patients with the four-gene methylation profile exhibited poorer disease-free survival than those without methylation. A significant effect of the four-gene methylation status on overall survival and disease-free survival was observed in early stage I and II CRC patients (p = 0.0016 and p = 0.0230, respectively). Taken together, these results demonstrate that the combination of the methylation statuses of NKX6.1, LMX1A, SOX1, and ZNF177 creates a novel prognostic panel that could be considered a molecular marker for outcomes in CRC patients.

NKX6.1 hypermethylation predicts the outcome of stage II colorectal cancer patients undergoing chemotherapy.

Colorectal cancer (CRC) is a common malignancy worldwide. CRC patients in the same stage often present with dramatically different clinical scenarios. Thus, robust prognostic biomarkers are urgently needed to guide therapies and improve treatment outcomes. The NKX6.1 gene has been identified as a hypermethylation marker in cervical cancer, functioning as a metastasis suppressor by regulating epithelial-mesenchymal transition. Here, we investigated whether hypermethylation of NKX6.1 might be a prognostic biomarker for CRC. By analyzing the methylation and expression of NKX6.1 in CRC tissues and CRC cell lines. We quantitatively examined the NKX6.1 methylation levels in 151 pairs of CRC tissues by using methylation-specific polymerase chain reaction analysis and found that NKX6.1 was hypermethylated in 35 of 151 CRC tissues (23%). NKX6.1 gene expression was inversely correlated with the DNA methylation level in CRC cell lines in vitro. Then, we analyzed the association of NKX6.1 methylation with clinical characteristics of these CRC patients. Our data demonstrated that patients with NKX6.1 methylation presented poorer 5-year overall survival (P = 0.0167) and disease-free survival (P = 0.0083) than patients without NKX6.1 methylation after receiving adjuvant chemotherapy. Most importantly, these data revealed that stage II CRC patients with NKX6.1 methylation had poorer 5-year disease-free survival (P = 0.0322) than patients without NKX6.1 methylation after adjuvant chemotherapy. Our results demonstrate that methylation of NKX6.1 is a novel prognostic biomarker in CRC and that it may be used as a predictor of the response to chemotherapy.

Risk of colorectal cancer in patients with periodontal disease severity: a nationwide, population-based cohort study.

BACKGROUND: Periodontal disease (PD) and colorectal cancer (CRC) were associated with chronic inflammation. This retrospective cohort study examined the association between PD severity and CRC in a large-scale, population-based Chinese cohort. METHODS: A total of approximately 106,487 individuals with newly diagnosed PD and 106,487 age-matched and sex-matched patients without PD from 2000 to 2002 were identified from Taiwan's National Health Insurance Research Database (NHIRD). RESULTS: The Kaplan-Meier analysis revealed that the cumulative incidence of CRC was significantly higher in patients with PD than in those without PD (log-rank test, P < 0.001). After adjustment for age, sex, and comorbidities, patients with PD were associated with a significantly higher risk of CRC compared with those without PD (adjusted HR = 1.64, 95% CI = 1.50-1.80). Further, the risk of CRC appeared to increase with increasing frequency of PD medical visits [adjusted HR (95% CI) was 1.78 (1.58-2.02) and 1.53 (1.35-1.74) for annual visits > 10 and < 4, respectively]. CONCLUSION: Based on our study, PD severity was associated with an increase in the risk of CRC. Further mechanistic research is needed.

Genistein suppresses leptin-induced proliferation and migration of vascular smooth muscle cells and neointima formation.

Obesity is a strong risk factor for the development of cardiovascular diseases and is associated with a marked increase in circulating leptin concentration. Leptin is a peptide hormone mainly produced by adipose tissue and is regulated by energy level, hormones and various inflammatory mediators. Genistein is an isoflavone that exhibits diverse health-promoting effects. Here, we investigated whether genistein suppressed the atherogenic effect induced by leptin. The A10 cells were treated with leptin and/or genistein, and then the cell proliferation and migration were analysed. The reactive oxygen species (ROS) and proteins levels were also measured, such as p44/42MAPK, cell cycle-related protein (cyclin D1 and p21) and matrix metalloproteinase-2 (MMP-2). Immunohistochemistry and morphometric analysis were used for the neointima formation in a rat carotid artery injury model. Genistein (5 µM) significantly inhibited both the proliferation and migration of leptin (10 ng/ml)-stimulated A10 cells. In accordance with these finding, genistein decreased the leptin-stimulated ROS production and phosphorylation of the p44/42MAPK signal transduction pathway. Meanwhile, genistein reversed the leptin-induced expression of cyclin D1, and cyclin-dependent kinase inhibitor, p21. Genistein attenuated leptin-induced A10 cell migration by inhibiting MMP-2 activity. Furthermore, the leptin (0.25 mg/kg)-augmented neointima formation in a rat carotid artery injury model was attenuated in the genistein (5 mg/kg body weight)-treated group when compared with the balloon injury plus leptin group. Genistein was capable of suppressing the atherogenic effects of leptin in vitro and in vivo, and may be a promising candidate drug in the clinical setting.

Echocardiographic function evaluation in adolescents following BNT162b2 Pfizer-BioNTech mRNA vaccination: A preliminary prospective study.

BACKGROUND: Vaccination against coronavirus disease 2019 (COVID-19) is crucial for preventing and minimizing illness. Myocarditis and pericarditis after messenger RNA (mRNA) COVID-19 vaccination in adolescents and young adult males have been reported. Most of the studies in this area rely on retrospective symptom reporting, especially for adolescents experiencing myocarditis as a potential side effect. However, prospective postvaccination echocardiographic evaluation is rare. METHODS: The study enrolled adolescents aged 12 to 15 years who received the second dose of the BNT162b2 Pfizer-BioNTech mRNA (BNT) vaccine. Serial echocardiographic examinations were conducted at baseline before vaccination, followed by subsequent assessments on days 2, 7, 14, and 28 to identify any notable differences or abnormal changes in cardiac function. Clinical symptom assessments were also recorded during each follow-up. RESULTS: The study included 25 adolescents, comprising 14 males and 11 females, who completed the four follow-ups. Their mean age was 14 ± 1 years. The average interval between the first and second BNT vaccine doses was 90 ± 7 days. Ejection fraction values were 73.8% ± 5.2% at baseline, followed by 75.7% ± 5.3%, 75.5% ± 4.6%, 75.7% ± 4.5%, and 77.8% ± 5.8% at day 2, 7, 14, and 28, respectively. The cardiac function remained stable across all time points, with no significant differences observed between male and female participants. Within postvaccination 48 hours, 18 (72%) of the enrolled adolescents experienced temporary discomfort symptoms, which completely resolved by the final follow-up on the 28th day after vaccination. CONCLUSION: Although adolescents vaccinated with the second dose of BNT vaccine commonly experienced transient postvaccination discomfort, the serial echocardiographic examinations did not reveal any significant deterioration of cardiac function within 28 days. Further studies are required to investigate the incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccination-associated myocarditis in adolescents and the related mechanisms.

Predicting the progress of colon cancer by DNA methylation markers of the p16 gene in feces - Evidence from an animal model.

A new noninvasive screening tool for colorectal neoplasia detects epigenetic alterations exhibited by gastrointestinal tumor cells shed into stool. There is insufficient existing data to determine temporal associations between colorectal cancer (CRC) progression and aberrant DNA methylation. To evaluate the feasibility of using fecal DNA methylation status to determine CRC progression, we collected stool samples from 14 male SD rats aged six weeks, and administered subcutaneous injections of either 1,2-dimethylhydrazine or saline weekly. p16 DNA methylation statuses in tumorous and normal colon tissue, and from stool samples were determined using methylation-specific PCR. Additionally, p16 methylation was detected in stool DNA from 85.7% of the CRC rats. The earliest change in p16 methylation status in the DMH-treated group stool samples occurred during week nine; repeatabilities were 57.1% in week 19 (p = 0.070) and 85.7% in week 34 (p = 0.005). A temporal correlation was evidenced between progression of CRC and p16 methylation status, as evidenced by DMH-induced rat feces. Using fecal DNA methylation status to determine colorectal tissue methylation status can reveal CRC progression. Our data suggests that p16 promoter methylation is a feasible epigenetic marker for the detection and may be useful for CRC screening.

Susceptibility to Colorectal Cancer Based on HSD17B4 rs721673 and rs721675 Polymorphisms and Alcohol Intake among Taiwan Biobank Participants: A Retrospective Case Control Study Using the Nationwide Claims Data.

Colorectal cancer (CRC) is a major public health issue, and there are limited studies on the association between 17ß-hydroxysteroid dehydrogenase type 4 (HSD17B4) polymorphism and CRC. We used two national databases from Taiwan to examine whether HSD17B4 rs721673, rs721675, and alcohol intake were independently and interactively correlated with CRC development. We linked the Taiwan Biobank (TWB) participants' health and lifestyle information and genotypic data from 2012 to 2018 to the National Health Insurance Database (NHIRD) to confirm their medical records. We performed a genome-wide association study (GWAS) using data from 145 new incident CRC cases and matched 1316 healthy, non-CRC individuals. We calculated the odds ratios (OR) and 95% confidence intervals (CI) for CRC based on multiple logistic regression analyses. HSD17B4 rs721673 and rs721675 on chromosome 5 were significantly and positively correlated with CRC (rs721673 A > G, aOR = 2.62, p = 2.90 × 10-8; rs721675 A > T, aOR = 2.61, p = 1.01 × 10-6). Within the high-risk genotypes, significantly higher ORs were observed among the alcohol intake group. Our results demonstrated that the rs721673 and rs721675 risk genotypes of HSD17B4 might increase the risk of CRC development in Taiwanese adults, especially those with alcohol consumption habits.

Application of Sonographic Assessments of the Rate of Proximal Progression to Monitor Protobothrops mucrosquamatus Bite-Related Local Envenomation: A Prospective Observational Study.

Patients bitten by Protobothrops mucrosquamatus typically experience significant pain, substantial swelling, and potentially blister formation. The appropriate dosage and efficacy of FHAV for alleviating local tissue injury remain uncertain. Between 2017 and 2022, 29 snakebite patients were identified as being bitten by P. mucrosquamatus. These patients underwent point-of-care ultrasound (POCUS) assessments at hourly intervals to measure the extent of edema and evaluate the rate of proximal progression (RPP, cm/hour). Based on Blaylock's classification, seven patients (24%) were classified as Group I (minimal), while 22 (76%) were classified as Group II (mild to severe). In comparison to Group I patients, Group II patients received more FHAV (median of 9.5 vials vs. two vials, p-value < 0.0001) and experienced longer median complete remission times (10 days vs. 2 days, p-value < 0.001). We divided the Group II patients into two subgroups based on their clinical management. Clinicians opted not to administer antivenom treatment to patients in Group IIA if their RPP decelerated. In contrast, for patients in Group IIB, clinicians increased the volume of antivenom in the hope of reducing the severity of swelling or blister formation. Patients in Group IIB received a significantly higher median volume of antivenom (12 vials vs. six vials; p-value < 0.001) than those in Group IIA. However, there was no significant difference in outcomes (disposition, wound necrosis, and complete remission times) between subgroups IIA and IIB. Our study found that FHAV does not appear to prevent local tissue injuries, such as swelling progression and blister formation, immediately after administration. When administering FHAV to patients bitten by P. mucrosquamatus, the deceleration of RPP may serve as an objective parameter to help clinicians decide whether to withhold FHAV administration.

Prophylactic hyperthermic intraperitoneal chemotherapy for patients with clinical T4 gastric cancer.

INTRODUCTION: Patients with clinical T4 gastric cancers have high recurrence rates and low 5-year overall survival (OS) despite radical gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy. The invisible peritoneal metastasis may result in local recurrence due to the tumor invading the serosa and nearby organs. Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested as an adjuvant treatment strategy in these patients. We evaluated the efficacy of prophylactic HIPEC post-gastrectomy for patients with clinical T4 gastric cancer. MATERIALS AND METHODS: We retrospectively reviewed data from 132 patients with clinical T4 gastric cancer who underwent gastrectomy + D2 lymphadenectomy between 2014 and 2020. Thirty-five of these patients also underwent prophylactic HIPEC perioperatively. We used propensity score matching (PSM) to reduce selection bias. We evaluated the risk factors for recurrence and compared the OS and disease-free survival (DFS) between the gastrectomy and prophylactic HIPEC groups. RESULTS: A total of 132 eligible patients were included in the study. Seventy preoperative patient characteristics were homogeneous post-PSM. Prophylactic HIPEC seemed to reduce the risk of postoperative peritoneal recurrence but did not influence the risk of distant metastasis. The risk factors for recurrence included advanced N stage, ascites, and lymphovascular invasion. OS (adjusted hazard ratio, 0.37; 95% CI, 0.17 to 0.81; p = 0.035) and DFS (adjusted hazard ratio, 0.33; 95% CI, 0.15 to 0.72; p = 0.017) were better in the prophylactic HIPEC group than in the gastrectomy alone group. CONCLUSIONS: Prophylactic HIPEC plus radical gastrectomy can reduce peritoneal recurrence and improve OS and DFS in patients with clinical T4 gastric cancer.

Applying the Student Response System in the Online Dermatologic Video Curriculum on Medical Students' Interaction and Learning Outcomes during the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted medical education worldwide. Online lecture is increasingly prevalent in higher education, but students' completion rate is quite low. Aims: This study aimed to determine the effectiveness of the student response system (SRS) in the online dermatologic video curriculum on medical students. Methods: A prospective study was conducted on 176 undergraduate fourth-year medical students. The online video lecture was integrated with SRS. Results: A total of 173 students completed the pre-test, and the attendance rate (pre-test/total) was 98.3%. A total of 142 students completed the post-test, and the completion rate (post-test/pre-test) was 82.8%. The post-test score (83.69 ± 4.34) was found to be significantly higher than that of the pre-test (62.69 ± 6.08, P =0.0002). A total of 138 students completed the questionnaire, and 92% of students opined that SRS was easy to operate. 86% of students agreed with the fact that the use of SRS could increase their learning performance by interacting with teachers. In the open-ended question, students stated that SRS offered opportunities for student-faculty interaction, allowed them to get immediate feedback, and promote active participation. Conclusions: These results highlight that the integration of SRS in the online video curriculum increases students' completion rates and learning outcomes. Moreover, the SRS is easy to operate for the students and enhances student-faculty interaction. The SRS may be adopted in online learning during this challenging time.

Association between serum uric acid levels and colonic diverticulosis in terms of sex.

BACKGROUND: The association between elevated serum uric acid (UA) levels and the risk of developing colonic diverticulosis has not yet been investigated. Thus, this cross-sectional study aimed to examine this correlation in individuals from Taiwan. METHODS: From Jan. 1, 2010, to Dec. 31, 2016., approximately 5,605 patients (aged >20 years) from Tri-Service General Hospital who met the inclusion criteria according to colonoscopy and laboratory test findings were included in this research. The correlation between serum UA levels and colonic diverticulosis was investigated via regression analyses. RESULTS: Participants with elevated serum UA levels were at a higher risk of colonic diverticulosis. The area under the curve for serum UA levels was significantly higher in women than in men (0.651 [95% confidence interval: 0.596-0.707] vs. 0.55 [0.507-0.593]). There were specific trends in female-specific indicators for colonic diverticulosis across increasing quartiles of serum UA levels. CONCLUSIONS: Patients with elevated serum UA levels should be cautious regarding the development of colonic diverticulosis disorder in female. Moreover, prospective studies may provide additional information on the relationship between elevated serum UA levels and colonic diverticulosis.

The Combination of Sleep Disorders and Depression Significantly Increases Cancer Risk: A Nationwide Large-Scale Population-Based Study.

Introduction: Sleep disorders, depression, and cancer have become increasingly prevalent worldwide. However, it is unknown whether coexistence of sleep disorders and depression influences the risk of cancer development. Therefore, we conducted a nationwide population-based study to examine this association among patients in Taiwan. Materials and Methods: A total of 105,071 individuals diagnosed with cancer and 420,284 age- and sex-matched patients without a diagnosis of cancer between 2000 and 2015 were identified from Taiwan's National Health Insurance Research Database. The underlying chronic diseases of patients that may developed cancer were gathered and studied as the predictor. A multivariate Cox proportional odds model was used to estimate the crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) to estimate the interaction effect between sleep disorders and depression on the risk of cancer. Results: After adjusting for age, sex, comorbidities, and other covariates, the cancer group was associated with increased exposure to sleep disorders than the non-cancer group (aOR = 1.440, 95% CI = 1.392−1.489, p < 0.001). In addition, patients with both sleep disorders and depression were at an even higher risk for cancer than the general population (aOR = 6.857, p < 0.001). Conclusions: This retrospective cohort study shows that patients with both sleep disorders and depression are at a higher risk of cancer. Clinically, a meticulous cancer risk evaluation is recommended for patients with both sleep disorders and depression.

Differential DNA methylation analysis of SUMF2, ADAMTS5, and PXDN provides novel insights into colorectal cancer prognosis prediction in Taiwan.

BACKGROUND: Patients with colorectal cancer (CRC) undergo surgery, as well as perioperative chemoradiation or adjuvant chemotherapy primarily based on the tumor-node- metastasis (TNM) cancer staging system. However, treatment responses and prognostic outcomes of patients within the same stage vary markedly. The potential use of novel biomarkers can improve prognostication and shared decision making before implementation into certain therapies. AIM: To investigate whether SUMF2, ADAMTS5, and PXDN methylation status could be associated with CRC prognosis. METHODS: We conducted a Taiwanese cohort study involving 208 patients with CRC recruited from Tri-Service General Hospital and applied the candidate gene approach to identify three genes involved in oncogenesis pathways. A methylation-specific polymerase chain reaction (MS-PCR) and EpiTYPER DNA methylation analysis were employed to detect methylation status and to quantify the methylation level of candidate genes in tumor tissue and adjacent normal tissue from participants. We evaluated SUMF2, ADAMTS5, and PXDN methylation as predictors of prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS), using a Cox regression model and Kaplan-Meier analysis. RESULTS: We revealed various outcomes related to methylation and prognosis. Significantly shorter PFS and OS were associated with the CpG_3+CpG_7 hypermethylation of SUMF2 from tumor tissue compared with CpG_3+CpG_7 hypomethylation [hazard ratio (HR) = 2.24, 95% confidence interval (CI) = 1.03-4.85 for PFS, HR = 2.56 and 95%CI = 1.08-6.04 for OS]. By contrast, a significantly longer RFS was associated with CpG_2 and CpG_13 hypermethylation of ADAMTS5 from normal tissue compared with CpG_2 and CpG_13 hypomethylation [HR (95%CI) = 0.15 (0.03-0.71) for CpG_2 and 0.20 (0.04-0.97) for CpG_13]. The relationship between the methylation status of PXDN and the prognosis of CRC did not reach statistical significance. CONCLUSION: Our study found that CpG_3+CpG_7 hypermethylation of SUMF2 from tumor tissue was associated with significantly shorter PFS and OS compared with CpG_3+CpG_7 hypomethylation. CpG_2 and CpG_13 hypermethylation of ADAMTS5 from normal tissue was associated with a significantly longer RFS compared with CpG_2 and CpG_13 hypomethylation. These methylation-related biomarkers which have implications for CRC prognosis prediction may aid physicians in clinical decision-making.

MTNR1B polymorphisms with CDKN2A and MGMT methylation status are associated with poor prognosis of colorectal cancer in Taiwan.

BACKGROUND: Identifying novel colorectal cancer (CRC) prognostic biomarkers is crucial to helping clinicians make appropriate therapy decisions. Melatonin plays a major role in managing the circadian rhythm and exerts oncostatic effects on different kinds of tumours. AIM: To explore the relationship between MTNR1B single-nucleotide polymorphism (SNPs) combined with gene hypermethylation and CRC prognosis. METHODS: A total of 94 CRC tumour tissues were investigated. Genotyping for the four MTNR1B SNPs (rs1387153, rs2166706, rs10830963, and rs1447352) was performed using multiplex polymerase chain reaction. The relationships between the MTNR1B SNPs and CRC 5-year overall survival (OS) was assessed by calculating hazard ratios with 95%CIs. RESULTS: All SNPs (rs1387153, rs2166706, rs10830963, and rs1447352) were correlated with decreased 5-year OS. In stratified analysis, rs1387153, rs10830963, and rs1447352 risk genotype combined with CDKN2A and MGMT methylation status were associated with 5-year OS. A strong cumulative effect of the four polymorphisms on CRC prognosis was observed. Four haplotypes of MTNR1B SNPs were also associated with the 5-year OS. MTNR1B SNPs combined with CDKN2A and MGMT gene methylation status could be used to predict shorter CRC survival. CONCLUSION: The novel genetic biomarkers combined with epigenetic biomarkers may be predictive tool for CRC prognosis and thus could be used to individualise treatment for patients with CRC.

Synthesis and conductivity enhancement of Al-doped ZnO nanorod array thin films.

Al-doped ZnO (AZO) nanorod array thin films with various Al/Zn molar ratios were synthesized by chemical bath deposition. The resultant AZO nanorods were well-aligned at the glass substrate, growing vertically along the c-axis [001] direction. In addition, they had an average diameter of 64.7 +/- 16.8 nm and an average length of about 1.0 microm with the structure of wurtzite-type ZnO. Analyses of energy dispersive x-ray spectra and x-ray photoelectron spectra indicated that Al atoms had been doped into the ZnO crystal lattice. The doping of Al atoms did not result in significant changes in the structure and crystal orientation, but the electrical resistivity was found to increase first and then decrease with increasing Al content owing to the increase of carrier concentration and the decrease of mobility. In addition, the transmission in the visible region increased but the increase was reduced at higher Al doping levels. After hydrogen treatment, the morphology of the AZO nanorod array thin films remained unchanged. However, the electrical resistivity decreased significantly due to the formation of oxygen vacancies and interstitial hydrogen atoms. When the real Al/Zn molar ratio was about 3.7%, the conductivity was enhanced about 1000 times and a minimum electrical resistivity of 6.4 x 10( - 4) Omega cm was obtained. In addition, the transmission of the ZnO nanorod array thin film in the visible region was significantly increased but the increase was less significant for the AZO nanorod array thin film, particularly at higher Al doping levels. In addition, the current-voltage curves of the thin film devices with ZnO or AZO nanorod arrays revealed that AZO had a higher current response than ZnO and hydrogen treatment led to a more significant enhancement of current responses (about 100-fold).

Risk for Irritable Bowel Syndrome in Patients with Helicobacter Pylori Infection: A Nationwide Population-Based Study Cohort Study in Taiwan.

BACKGROUND: The association between Helicobacter pylori (H. pylori) infection and the risk of developing irritable bowel syndrome (IBS) has yet to be investigated; thus, we conducted this nationwide cohort study to examine the association in patients from Taiwan. METHODS: A total of approximately 2669 individuals with newly diagnosed H. pylori infection and 10,676 age- and sex-matched patients without a diagnosis of H. pylori infection from 2000 to 2013 were identified from Taiwan's National Health Insurance Research Database. The Kaplan-Meier method was used to determine the cumulative incidence of H. pylori infection in each cohort. Whether the patient underwent H. pylori eradication therapy was also determined. RESULTS: The cumulative incidence of IBS was higher in the H. pylori-infected cohort than in the comparison cohort (log-rank test, p < 0.001). After adjustment for potential confounders, H. pylori infection was associated with a significantly increased risk of IBS (adjusted hazard ratio (aHR) 3.108, p < 0.001). In addition, the H.pylori-infected cohort who did not receive eradication therapy had a higher risk of IBS than the non-H. pylori-infected cohort (adjusted HR 4.16, p < 0.001). The H.pylori-infected cohort who received eradication therapy had a lower risk of IBS than the comparison cohort (adjusted HR 0.464, p = 0.037). CONCLUSIONS: Based on a retrospective follow-up, nationwide study in Taiwan, H. pylori infection was associated with an increased risk of IBS; however, aggressive H. pylori infection eradication therapy can also reduce the risk of IBS. Further underlying biological mechanistic research is needed.

Author Correction: Multiple gene promoter methylation and clinical stage in adjacent normal tissues: Effect on prognosis of colorectal cancer in Taiwan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.