Impact of polygenic risk score for triglyceride trajectory and diabetic complications in subjects with type 2 diabetes based on large electronic medical record data from Taiwan: a case control study.

BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

Association of radiotherapy for prostate cancer and second primary colorectal cancer: a US population-based analysis.

BACKGROUND: Radiotherapy (RT) is a common treatment for prostate cancer, yet the risk of second primary colorectal cancer (SPCRC) in patients with prostate cancer undergoing RT has not been adequately studied. METHODS: This study employed a population-based cohort design using the US Surveillance, Epidemiology, and End Results (SEER) database to identify individuals diagnosed between January 1975 and December 2015. The cumulative incidence of SPCRC was estimated using Fine-Gray competing risk regression. Poisson regression analysis was used to estimate the risk associated with RT. Survival outcomes of patients with SPCRC were evaluated using the Kaplan-Meier method. RESULTS: A total of 287,607 patients diagnosed with prostate cancer were identified. The cumulative incidences were higher in patients who did not receive RT (2.00%) compared to those who underwent RT (2.47%) after 25 years. After adjustment for multiple variables, RT was associated with an increased risk of developing combined SPCRC (adjusted HR 1.590). Additionally, the overall survival was significantly lower in patients who developed colorectal cancer after receiving RT as compared to those who did not receive RT. CONCLUSION: These findings underscore the need for diligent long-term monitoring and effective management strategies to detect SPCRC in patients treated with RT for prostate cancer.

Age-related genes affecting the immune cell infiltration in ulcerative colitis revealed by weighted correlation network analysis and machine learning.

OBJECTIVE: The crosstalk between age and immunity in the context of ulcerative colitis (UC) remains incompletely understood. Our objective is to elucidate the specific age-associated genetic factors that modulate immune cell infiltration in UC, with the aim of identifying innovative therapeutic targets for the treatment of this disease. MATERIALS AND METHODS: Potential batch effects between samples were removed by R package "inSilicoMerging". Unsupervised clustering analysis via the "ConsensusClusterPlus" R package was utilized to perform consensus molecular subtyping of immune subtypes in UC. The construction of a heat map was accomplished through the utilization of the R package "pheatmap", while functional enrichment analysis was executed by means of the Metascape database. The identification of the age-related gene module was achieved by performing weighted gene co-expression network analysis (WGCNA) analysis using the R package "WGCNA". The support vector machine (SVM), least absolute shrinkage and selector operation (LASSO), and random forest algorithms were performed via the "e1071", "glmnet" and "randomForest" packages in R, respectively. The diagnostic performance of the parameter was assessed using the receiver operating characteristic (ROC) curve. Correlation analysis was performed by Spearman correlation. The "XSum" package in R was employed to identify potential small-molecule drugs for UC utilizing the Connectivity Map (CMap) database. Molecular docking was performed with Autodock Vina molecular docking software. RESULTS: A significantly greater frequency of UC patients aged below 40 years was observed in the group with extensive disease extent as compared to those with non-extensive disease extent (70% vs. 47%; Chi-square test, p = 0.02). The application of unsupervised clustering analysis allowed for the stratification of UC patients into two distinct immune subtypes, namely cluster C1 and cluster C2. The distribution of immune subtypes was significantly different between different age categories (Chi-square test,  p = 0.00219). The UC samples that were grouped under cluster C1 were distinguished by a higher abundance of macrophages and an elevated number of neutrophils relative to those in cluster C2. Based on both WGCNA and Limma analysis, 146 age-related genes were identified, which exhibited a predominant enrichment in the biological process of cellular senescence. Two age-related genes (MIDN, and PLD6) affecting the immune cell infiltration in UC were identified based on machine learning algorithms (SVM, LASSO, and random forest). The diagnostic performance of MIDN (AUC = 0.93) and PLD6 (AUC = 0.90) in discerning UC patients belonging to cluster C1 was found to be satisfactory, as demonstrated by ROC curve analysis. MIDN demonstrated a positive correlation (r = 0.50,  p < 0.0001) with Neutrophil, while PLD6 exhibited a negative correlation (r = -0.52, p < 0.0001) with Neutrophil levels. The "XSum" algorithm revealed that Entinostat has therapeutic potential for UC. The docking glide score between Entinostat and MIDN, and PLD6 protein was -8.9 kcal/mol and -6.8 kcal/mol, respectively. CONCLUSIONS: We have identified two age-related genes, MIDN and PLD6, that are involved in immune cell infiltration in patients with ulcerative colitis. Furthermore, a small molecule drug (Entinostat) with potential therapeutic effects for UC was screened out. This study presented new perspectives on personalized clinical management and therapy research for UC.

Zoledronic acid epigenetically alleviates high-glucose-suppressed osteogenic differentiation of MC3T3-E1 cells.

OBJECTIVE: Due to the impact of excessive glucose on osteogenic differentiation, diabetic osteopathy frequently results in skeletal fragility, osteoporosis, and bone pain. Zoledronic acid, a bisphosphonate (BP) that effectively inhibits osteoclastic bone resorption is given yearly to improve bone mineral density (BMD) in patients with osteoporosis. However, the detailed molecular mechanisms remained unclear. This study investigates the possible pathways by which zoledronic acid regulates osteogenesis when blood glucose levels are high. MATERIALS AND METHODS: MC3T3-E1 cells were treated with one mM zoledronic acid or not in a standard or high glucose culture medium. A quantitative polymerase chain reaction (qPCR) assay was utilized to assess the expression of the target candidate genes, including RUNX2, MALAT1, miR-133, miR-20a, and miR-204. RESULTS: In a high-glucose condition, zoledronic acid treatment significantly lowered MALAT1 (p < 0.0001) and miR-20a (p < 0.0001) expression. Conversely, in a high-glucose condition, RUNX2, miR-133, and miR-204 expressions were found to be significantly increased in the zoledronic acid treatment group as compared to no treatment (all p < 0.0001). CONCLUSIONS: In conclusion, under a high-glucose environment, zoledronic acid can modulate the expression of the RUNX2 transcription factor through epigenetic regulation.

A binary pulsar in a 53-minute orbit.

Spider pulsars are neutron stars that have a companion star in a close orbit. The companion star sheds material to the neutron star, spinning it up to millisecond rotation periods, while the orbit shortens to hours. The companion is eventually ablated and destroyed by the pulsar wind and radiation1,2. Spider pulsars are key for studying the evolutionary link between accreting X-ray pulsars and isolated millisecond pulsars, pulsar irradiation effects and the birth of massive neutron stars3-6. Black widow pulsars in extremely compact orbits (as short as 62 minutes7) have companions with masses much smaller than 0.1 M⊙. They may have evolved from redback pulsars with companion masses of about 0.1-0.4 M⊙ and orbital periods of less than 1 day8. If this is true, then there should be a population of millisecond pulsars with moderate-mass companions and very short orbital periods9, but, hitherto, no such system was known. Here we report radio observations of the binary millisecond pulsar PSR J1953+1844 (M71E) that show it to have an orbital period of 53.3 minutes and a companion with a mass of around 0.07 M⊙. It is a faint X-ray source and located 2.5 arcminutes from the centre of the globular cluster M71.

Evaluation of cold atmospheric plasma for the decontamination of flexible endoscopes.

BACKGROUND: Despite adherence to standard protocols, residues including live micro-organisms may remain on the various surfaces of reprocessed flexible endoscopes. Prions are infectious proteins that are notoriously difficult to eliminate. AIM: To test the potential of cold atmospheric plasma (CAP) for the decontamination of various surfaces of flexible endoscopes, measuring total proteins and prion residual infectivity as indicators of efficacy. METHODS: New PTFE endoscope channels and metal test surfaces spiked with test soil or prion-infected tissues were treated using different CAP-generating prototypes. Surfaces were examined for the presence of residues using very sensitive fluorescence epimicroscopy. Prion residual infectivity was determined using the wire implant animal model and a more sensitive cell infectivity assay. FINDINGS: A CAP jet applied perpendicularly at close range on flat test surfaces removed soil within 3 min, but left microscopic residues and failed to eliminate prion infectivity according to the wire implant animal assay. The longitudinal gas flow from CAP prototypes developed for the treatment of long channels led to the displacement and sedimentation of residual soil towards the distal end, when applied alone. Observations of the plasma inside glass tubes showed temporal and spatial heterogeneity within a limited range. After the standard enzymatic manual pre-wash, 'CAP-activated' gas effluents prevented prion transmission from treated endoscope channels according to the prion infectivity cell assay. CONCLUSION: CAP shows promising results as a final step for decontamination of surgical surfaces. Optimizing CAP delivery could further enhance CAP efficacy, offering a safe, chemical-free alternative for the reprocessing of all luminal flexible endoscope surfaces.

SP1-induced lncRNA DUBR promotes stemness and oxaliplatin resistance of hepatocellular carcinoma via E2F1-CIP2A feedback.

Oxaliplatin-based chemotherapy is widely used to treat advanced hepatocellular carcinoma (HCC), but many patients develop drug resistance that leads to tumor recurrence. Cancer stem cells (CSCs) are known to contribute to chemoresistance, the underlying mechanism, however, remains largely unknown. In this study, we discovered a specificity protein 1 (SP1)-induced long noncoding RNA--DPPA2 upstream binding RNA (DUBR) and its high expression in HCC tissues and liver CSCs. DUBR was associated with HCC progression and poor chemotherapy response. Moreover, DUBR facilitated the stemness and oxaliplatin resistance of HCC in vitro and in vivo. Mechanistically, DUBR upregulated cancerous inhibitor of protein phosphatase 2A (CIP2A) expression through E2F1-mediated transcription regulation. DUBR also exerted function by binding microRNA (miR)-520d-5p as a competing endogenous RNA to upregulate CIP2A at mRNA level. CIP2A, in turn, stabilized E2F1 protein and activated the Notch1 signaling pathway, thereby increasing the stemness feature of HCC and leading to chemoresistance. In conclusion, we identified SP1/DUBR/E2F1-CIP2A as a critical axis to activate the Notch1 signaling pathway and promote stemness and chemoresistance of HCC. Therefore, DUBR could be a potential target in HCC treatment.

Insurance status and risk of suicide mortality among patients with cancer: a retrospective study based on the SEER database.

OBJECTIVE: Given that the presence of insurance may affect the risk of suicide mortality in cancer patients, we aimed to examine the association in a population-based study using the Surveillance, Epidemiologic, and End Results (SEER) database. STUDY DESIGN: A retrospective analysis of data from the SEER database. METHODS: We conducted a retrospective study using the SEER database. Hazard ratios (HRs), adjusted HRs (aHRs), and 95% confidence intervals (95% CIs) of suicide death were calculated using Cox proportional hazard models to evaluate the risk of suicide mortality among the cohorts. RESULTS: Multivariable analysis revealed that cancer patients without insurance had an increased risk of suicide death compared with patients with private insurance (aHR, 1.37; 95% CI, 1.01-1.72), whereas no significant result was observed in patients with any Medicaid (aHR, 1.10; 95% CI, 0.93-1.30; P = 0.27). In addition, the stratified analysis indicated that the risk of suicide death in patients in the uninsured and Medicaid groups presented with localized stage of disease (aHR, 1.32; 95% CI, 1.02, 1.69), White (aHR, 1.34; 95% CI, 1.05, 1.71), and American Indian/Alaska Native and Asian/Pacific Islander (aHR, 1.89; 95% CI, 1.08, 3.30) were greater than insured patients. CONCLUSION: Overall, our results indicated that insurance status was a statistically significant predictor of suicide death in patients with cancer. Healthcare providers should identify those patients at high risk of suicide and provide appropriate mental health and psychosocial oncology services in time.

LncRNA DCST1-AS1 accelerates the proliferation, metastasis and autophagy of hepatocellular carcinoma cell by AKT/mTOR signaling pathways.

OBJECTIVE: The previous research revealed that long noncoding RNAs (lncRNAs) play a vital role in the development of hepatocellular carcinoma (HCC). To further discuss the underlying mechanisms of lncRNA DCST1-AS1 in the pathogenesis of HCC. PATIENTS AND METHODS: We screened the abnormally expressed genes in HCC tissues through microarray analysis and found that lncRNA DCST1-AS1 was one of the genes significantly up-regulated. Real Time-Polymerase Chain Reaction (RT-qPCR) was used to test the gene expression of lncRNA DCST1-AS1 in HCC tissues and HepG2 cells. Respectively, CCK-8 assay, flow cytometry detection, transwell assay, wound healing assay, transmission electron microscopy, and immunofluorescence staining were used to assess the proliferation, apoptosis, migration, and autophagy of HepG2 cells. Meanwhile, the expression of signaling pathway proteins was detected by Western blot. RESULTS: LncRNA DCST1-AS1 was confirmed hyper-expression both in HCC tissues and HCC cells. High expression of lncRNA DCST1-AS1 was significantly correlated with inferior prognosis. Moreover, lncRNA DCST1-AS1 depletion suppressed proliferation and accelerated apoptosis, activated cycle arrest, restrained cell migration, and stimulated autophagy in HCC cells. In addition, it is found that the depletion of lncRNA DCST1-AS1 on HepG2 cells exhibits anti-tumor characteristics and was mediated by the AKT/mTOR signal transduction pathway. Furthermore, pre-treated HepG2 cells with SC79, an AKT signal activator, partially restored the effect of lncRNA DCST1-AS1 silencing on HepG2 cell proliferation, apoptosis, migration, and autophagy. CONCLUSIONS: Our results suggested that lncRNA DCST1-AS1, as a carcinogenic factor in HCC, promoted cell proliferation, and invasion, inhibited apoptosis and autophagy by modulating the AKT/mTOR signaling cascade. Therefore, our findings showed that lncRNA DCST1-AS1 may improve potential treatment strategies for HCC.

RUNX3 protects against acute lung injury by inhibiting the JAK2/STAT3 pathway in rats with severe acute pancreatitis.

OBJECTIVE: Acute lung injury (ALI) is the most common complication of severe acute pancreatitis (SAP) in the early stage, which causes systemic inflammatory response and organ damage. Human runt-associated transcription factor 3 gene (RUNX3) has been reported to participate in various inflammatory diseases. However, the exact role of RUNX3 in SAP and its-related ALI remains unclear. MATERIALS AND METHODS: To establish the model of SAP, rats were retrogradely injected with 5% sodium taurocholate (1 mg/kg body weight) into the biliary-pancreatic duct. Cytokine level in serum was measured by ELISA, and the polymorphonuclear neutrophil (PMN) was isolated from rat's blood 12 h-post SAP induction. RESULTS: We found RUNX3 expression was significantly decreased with the progression of SAP. Both pancreas damages and cytokine production abilities were reduced in RUXN3-overexpressed SAP rats compared with control rats. Moreover, SAP-associated ALI was also improved upon RUNX3 overexpression in SAP rats. RUNX3 upregulation enhanced PMN apoptosis and inhibited Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) phosphorylation. CONCLUSIONS: Our study indicates that RUNX3 protects against SAP and SAP-associated ALI through controlling PMN apoptosis and regulating JAK2/STAT3 signaling pathway. RUNX3 could be regarded as a potent therapeutic target in SAP for future studies.

Correlated optical and structural analyses of individual GaAsP/GaP core-shell nanowires.

We report on the structural and optical properties of GaAs0.7P0.3/GaP core-shell nanowires (NWs) for future photovoltaic applications. The NWs are grown by self-catalyzed molecular beam epitaxy. Scanning transmission electron microscopy (STEM) analyses demonstrate that the GaAsP NW core develops an inverse-tapered shape with a formation of an unintentional GaAsP shell having a lower P content. Without surface passivation, this unintentional shell produces no luminescence because of strong surface recombination. However, passivation of the surface with a GaP shell leads to the appearance of a secondary peak in the luminescence spectrum arising from this unintentional shell. The attribution of the luminescence peaks is confirmed by correlated cathodoluminescence and STEM analyses of the same NW.

Behavioral and Structural Effects of Single and Repeat Closed-Head Injury.

BACKGROUND AND PURPOSE: The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure. MATERIALS AND METHODS: We introduced a repetitive closed-head injury rodent model (n = 70) without parenchymal lesions. We performed a longitudinal MR imaging study during a 50-day study period (T2-weighted imaging, susceptibility-weighted imaging, and diffusion tensor imaging) as well as sequential behavioral assessment. Immunohistochemical staining for astrogliosis was examined in a subgroup of animals. Paired and independent t tests were used to evaluate the outcome change after injury and the cumulative effects of impact load, respectively. RESULTS: There was no gross morphologic evidence for head injury such as skull fracture, contusion, or hemorrhage on micro-CT and MR imaging. A significant decrease of white matter fractional anisotropy from day 21 on and an increase of gray matter fractional anisotropy from day 35 on were observed. Smaller mean cortical volume in the double-injury group was shown at day 50 compared with sham and single injury (P < .05). Behavioral deficits (P < .05) in neurologic outcome, balance, and locomotor activity were also aggravated after double injury. Histologic analysis showed astrogliosis 24 hours after injury, which persisted throughout the study period. CONCLUSIONS: There are measurable and dynamic changes in microstructure, cortical volume, behavior, and histopathology after both single and double injury, with more severe effects seen after double injury. This work bridges cross-sectional evidence from human subject and pathologic studies using animal models with a multi-time point, longitudinal research paradigm.

Open peroral endoscopic myotomy (O-POEM) for the treatment of achalasia.

With the development of endoscopic interventions and inspired by the success of peroral endoscopic myotomy (POEM) for the treatment of achalasia, we investigated an old method of direct peroral endoscopic myotomy without a submucosal tunnel for the treatment of achalasia, which we call open peroral endoscopic myotomy (O-POEM). In this study, Clinical success was achieved in the patient after O-POEM. A reduction of LES pressure, Eckardt score, and a timed barium esophagogram were observed during follow-up. There were no severe complications and no recurrences during two months of follow-up. Therefore, open peroral endoscopic myotomy is a feasible and effective endoscopic treatment modality for achalasia. However, long-term outcomes of O-POEM requires further follow-up.

Xanthine dehydrogenase downregulation promotes TGFß signaling and cancer stem cell-related gene expression in hepatocellular carcinoma.

Xanthine dehydrogenase (XDH), a rate-limiting enzyme involved in purine metabolism, has an essential role in inflammatory cascades. Researchers have known for decades that XDH activity is decreased in some cancers, including hepatocellular carcinoma (HCC). However, the role of XDH in cancer pathogenesis has not been fully explored. In this study, we showed that low XDH mRNA levels were correlated with higher tumor stages and poorer prognoses in patients with HCC. Knocking down or inhibiting XDH promoted migration and invasion but not proliferation of HCC cells. The abovementioned phenotypic changes are dependent on increases in epithelial-mesenchymal transition marker gene expression and transforming growth factor-ß-Smad2/3 signaling activity in HCC. XDH overexpression suppressed HCC cell invasion in vitro and in vivo. In addition, the expression and activity of XDH were associated with the expression of CSC-related genes, such as CD44 or CD133, in HCC cells. These data suggest that downregulated XDH expression may be a useful clinical indicator and contribute to the development and progression of HCC.

Diabetes and pressure ulcer risk in hip fracture patients: a meta-analysis.

OBJECTIVE: The aim of this study was to assess the relationship between diabetes and pressure ulcer (PU) risk in patients with hip fractures. METHOD: Searches of MEDLINE (1966-), ISI Databases (1965-) and Scopus (1996-) were performed for English language studies. The search data was 29 July 2016. Odds ratio (OR) for PUs were calculated for hip fracture patients with or without diabetes and a meta-analysis was carried out following meta-analysis of observational studies in epidemiology (MOOSE) guidelines. RESULTS: A total of 8 studies with 22,180 patients were included in this study. The mean PU incidence was 15.1% in group with diabetes compared with 7.5% in the group without diabetes. When comparing with and without diabetes meta-analysis showed the summary OR was 1.825 [95% confidence interval (CI): 1.373-2.425; z=4.15, p<0.00001]. No significant publication bias was found. Sensitivity analysis included prospective studies [OR: 1.383, 95%CI: 1.035-1.847] and pooled the adjusted OR [OR: 1.282, 95%CI: 1.054-1.560] showed the result was robust. Subgroup analysis by PU stage showed the summary OR was 1.474 [95% CI 0.984-2.207] for ≥ category II PU, and 2.814 [95%CI: 2.115-3.742] for ≥category I PU. The meta-regression showed PU incidence explained 27.77% proportion of between-study variance, but statistical test showed no significance (t=-1.96, p=0.097). CONCLUSION: Our meta-analysis indicates that diabetes increases the PU risk in hip fracture patients. Therefore, specific recommendations should apply for the management of diabetic patients with hip fractures at risk of PU.

Efficacy of arginine-enriched enteral formulas for the healing of pressure ulcers: a systematic review.

OBJECTIVE: Arginine improves healing and modulates inflammation and the immune response. This systematic review aimed to assess the effect of arginine-enriched enteral formulas in pressure ulcer (PU) healing. METHOD: Systematic computerised searches of PubMed, Web of Knowledge, Scopus, ENTRAL and CINAHL databases were performed from their inception to 20 January 2016. Randomised controlled trials (RCTs) were included in this systematic review. We used the Jadad scale as a quality assessment tool. RESULTS: There were seven RCTs with 369 patients included in this systematic review; four RCTs assessed healing by PU area reduction. All of them reported arginine-enriched enteral nutrition led to a significant improved PU healing compared with standard hospital diet in 2-12 weeks follow-up. Among these four RCTs, one enrolled malnourished patients, one enrolled non-malnourished patients, and the other two studies did not restrict the nutritional status of the patients. Using the Pressure Ulcer Scale for Healing (PUSH) four RCTs assessed healing of PU, all reporting arginine-enriched enteral nutrition resulted in a significant PUSH score improvement compared with control at follow-up. Using the Pressure Sore Status Tool (PSST) one RCT assessed healing of PUs, finding patients receiving arginine had the lowest PSST scores compared with controls. An RCT compared healing with two doses of arginine (4.5g versus 9g), but no difference was found between the doses. CONCLUSION: Evidence showed that arginine-enriched enteral nutrition led to a significant improvement in PU healing. It was effective not only in malnourished patients, but also in non-malnourished patients.

Circulating levels of autoantibodies against L1-cell adhesion molecule as a potential diagnostic biomarker in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignant disease worldwide, especially in China. We aimed to determine the level of autoantibodies against L1CAM in patients with ESCC. METHODS: Levels of circulating autoantibodies against L1CAM antigens were determined by an enzyme-linked immunosorbent assay in cohort 1 (191 patients with ESCC and 94 normal controls) and validated in cohort 2 (47 patients with ESCC and 47 normal controls). Receiver-operating characteristics were employed to calculate diagnostic accuracy. Cumulative survival time was calculated by the Kaplan-Meier method and analyzed by the log-rank test. RESULTS: In cohorts 1 and 2, levels of autoantibodies against L1CAM were all significantly higher in sera of patients with ESCC compared to normal controls (P < 0.05). Detection of autoantibodies against L1CAM provided a sensitivity of 26.2%, a specificity of 90.4%, and an area under the curve (AUC) of 0.603 (95% CI 0.535-0.672) in diagnosing ESCC in cohort 1, and a sensitivity of 27.7%, a specificity of 91.5%, and an AUC of 0.628 (95% CI 0.516-0.741). Similar results were observed in the diagnosis of early stage ESCC (25.2% sensitivity, 90.4% specificity, and an AUC of 0.611 (95% CI 0.533-0.689) in cohort 1, and 33.3% sensitivity, 91.5% specificity, and an AUC of 0.636 (95% CI 0.439-0.832) in cohort 2). Moreover, positive rates of autoantibodies against L1CAM had no statistical correlation with clinical outcome of ESCC (P > 0.05). CONCLUSIONS: Our results suggest that circulating autoantibodies against L1CAM is a potential biomarker for the early detection of ESCC.

Chronologic changes in serum hepatitis B virus DNA, genotypes, surface antigen mutants and reverse transcriptase mutants during 25-year nationwide immunization in Taiwan.

We investigated breakthrough infection and hepatitis B virus (HBV) genetic changes in immunized subjects after 25 years of a universal infant immunization. Specifically, serum HBV DNA, genotypes, surface antigen mutants and nucleoside analog-resistant (NAr) mutants were assessed in 2853 subjects (<25 years old) surveyed in 2009, and these data were compared with the data from previous serosurveys. A comparison across different age-stratified groups using the 2009 data revealed a significant increase in the seropositive rate of anti-HBc (5.51% vs 12.38%, P=.001) and HBV DNA (1.13% vs 3.96%, P=.007) between those 17-22 and 23-24 years of age, possibly due to selective infant immunization in 1984-1986. Well-characterized NAr mutants, potential NAr mutants and surface "a" determinant mutants were detected in none, 15 (45.5%) and nine (27.3%) of 33 HBV DNA-positive subjects, respectively. Of 15 immunized, HBV DNA-positive young adults (18-24 years), three (20%) carried "a" determinant mutants. Amongst 1176 HBsAg-negative subjects evaluated for occult HBV infection, those seropositive for anti-HBc had a higher seropositive rate for HBV DNA (10/110, 9.1% vs 7/1066, 0.66%; P<.001) and "a" determinant mutants (4/110, 3.6% vs 0/1066; P<.001) than those seronegative for anti-HBc. Overall, the HBsAg-positive subjects in six serosurveys showed no significant increase in genotype C frequency in the comparison between the vaccinated and unvaccinated cohorts (25/98, 25.5% versus 14/79, 17.7%, P=.188). Over the 25-year programme, there was no increase in the prevalence of genotype C in HBsAg carriers and no increase in breakthrough HBV infection or surface mutant prevalence beyond adolescence. Nucleic acid amplification should still be considered the primary screening method for occult hepatitis B detection in high-risk recipients.