The diagnosis of EHM was based on imaging results from CT, MRI, US or bone scintigraphy. These tests were performed when we observed symptoms compatible with EHM, such as pain or neurological impairment, or when HCC-specific tumor markers were elevated. α-Fetoprotein (AFP), des-γ-carboxyprothrombin (DCP) and Lens culinaris agglutinin-reactive fraction of AFP were used as HCC-specific tumor markers. The association between EHM and 16 clinical parameters see more was analyzed. Variables

included platelet counts, sex, age, viral markers (hepatitis B virus [HBV] surface antigen and hepatitis C virus [HCV] antibody), maximum tumor size, number of tumors, vascular invasion, serum tumor markers (AFP and DCP), Child–Pugh class, albumin, total bilirubin, prothrombin time, aspartate aminotransferase (AST) and alanine aminotransferase. We determined the cut-off value of the laboratory data based on median value.

In the retrospective cohort study, we used the laboratory data on admission for the initial non-curative treatment (before the treatment). We included the variable “the presence of splenomegaly” in the analysis in addition to the 16 parameters. Logistic regression analysis was used in the case–control study. Variables that demonstrated a P-value of less than 0.05 in univariate analysis were click here entered into the multiple logistic regression model. Survival and incidence of extrahepatic metastasis was compared using the Kaplan–Meier method, RANTES and the difference was evaluated by log–rank test. Cox’s proportional hazard model was used for estimating the risk for EHM in the retrospective cohort study. All statistical analyses were performed using JMP version 9 software (JMP Japan,

Tokyo, Japan). All reported P-values are two-sided, and P < 0.05 was considered statistically significant. AT THE INITIAL treatment, there were 30 EHM positive patients and 1583 EHM negative patients (Table 1). The sites of EHM were as follows: lung in 14 patients, bone in 11, lymph node in 10, adrenal gland in three and peritoneum in two. Four patients had EHM in multiple organs. Median survival time was 3.4 months in EHM positive patients and 67 months in EHM negative. Univariate logistic regression analysis revealed that high platelet counts (>10 × 104/μL), maximum tumor size (>30 mm), number of tumors (≥4), the presence of vascular invasion, elevated DCP (>40 mAU/mL), elevated AST (>55 IU/L) and the presence of HCV antibody were significant risk factors for EHM (Table 2). In multivariate analysis of parameters that showed significant differences in univariate analysis, high platelet counts (odds ratio [OR] = 4.84; 95% confidence interval [CI] = 1.29−29.54; P = 0.01), multiple tumors (≥4) (OR = 3.01; 95% CI = 1.15−8.51; P = 0.02) and the presence of vascular invasion (OR = 6.94; 95% CI = 2.16−26.68; P = <0.001) were the risk factors for the presence of EHM. There were 602 men (75%) in the study, with median age of 69 years (range, 23−94).

The diagnosis of EHM was based on imaging results from CT, MRI, US or bone scintigraphy. These tests were performed when we observed symptoms compatible with EHM, such as pain or neurological impairment, or when HCC-specific tumor markers were elevated. α-Fetoprotein (AFP), des-γ-carboxyprothrombin (DCP) and Lens culinaris agglutinin-reactive fraction of AFP were used as HCC-specific tumor markers. The association between EHM and 16 clinical parameters find more was analyzed. Variables

included platelet counts, sex, age, viral markers (hepatitis B virus [HBV] surface antigen and hepatitis C virus [HCV] antibody), maximum tumor size, number of tumors, vascular invasion, serum tumor markers (AFP and DCP), Child–Pugh class, albumin, total bilirubin, prothrombin time, aspartate aminotransferase (AST) and alanine aminotransferase. We determined the cut-off value of the laboratory data based on median value.

In the retrospective cohort study, we used the laboratory data on admission for the initial non-curative treatment (before the treatment). We included the variable “the presence of splenomegaly” in the analysis in addition to the 16 parameters. Logistic regression analysis was used in the case–control study. Variables that demonstrated a P-value of less than 0.05 in univariate analysis were Staurosporine ic50 entered into the multiple logistic regression model. Survival and incidence of extrahepatic metastasis was compared using the Kaplan–Meier method, Teicoplanin and the difference was evaluated by log–rank test. Cox’s proportional hazard model was used for estimating the risk for EHM in the retrospective cohort study. All statistical analyses were performed using JMP version 9 software (JMP Japan,

Tokyo, Japan). All reported P-values are two-sided, and P < 0.05 was considered statistically significant. AT THE INITIAL treatment, there were 30 EHM positive patients and 1583 EHM negative patients (Table 1). The sites of EHM were as follows: lung in 14 patients, bone in 11, lymph node in 10, adrenal gland in three and peritoneum in two. Four patients had EHM in multiple organs. Median survival time was 3.4 months in EHM positive patients and 67 months in EHM negative. Univariate logistic regression analysis revealed that high platelet counts (>10 × 104/μL), maximum tumor size (>30 mm), number of tumors (≥4), the presence of vascular invasion, elevated DCP (>40 mAU/mL), elevated AST (>55 IU/L) and the presence of HCV antibody were significant risk factors for EHM (Table 2). In multivariate analysis of parameters that showed significant differences in univariate analysis, high platelet counts (odds ratio [OR] = 4.84; 95% confidence interval [CI] = 1.29−29.54; P = 0.01), multiple tumors (≥4) (OR = 3.01; 95% CI = 1.15−8.51; P = 0.02) and the presence of vascular invasion (OR = 6.94; 95% CI = 2.16−26.68; P = <0.001) were the risk factors for the presence of EHM. There were 602 men (75%) in the study, with median age of 69 years (range, 23−94).

Included were 133 adult and paediatric patients with a high suspicion of VWD. Fifty-three were diagnosed with VWD: 47 (88.7%) with type 1 VWD, four (7.5%) with type 2a VWD and two (3.8%) with type 3 VWD. Mean age for

female patients was 19.5 years (range 3–44 years) and 18.5 years (range 4–63 years) for male patients. Mean age at start of bleeding symptoms was 8.8 years (range 1–61). The most frequent clinical symptoms were epistaxis (84.9%), ecchymosis (79.2%), haematomas (71.7%), gum bleeds (62.3%) and petechia (50.9%). Severe transoperative or postoperative bleeding was found in 17 patients (32.1%). Twenty-six women at childbearing age had a history of abnormal gynaecological bleeding. Our results clearly demonstrate the presence of VWD in Mexican and underscore the importance of a more detailed description of VWD. http://www.selleckchem.com/products/Nutlin-3.html Efforts to increase the awareness and diagnosis of VWD could help in better identification of patients with bleeding disorders and lead to early, appropriate management with safe and efficacious therapies such as desmopressin and

plasma concentrates. “
“Joint bleeding is the hallmark of severe haemophilia and the major cause of disability in patients with this coagulopathy. Repeated bleeding into the same selleckchem joint can lead to chronic synovitis and progressive arthropathy. Radiosynovectomy is one option for the treatment of chronic haemophilic synovitis, but concerns about the risks of exposure

to ionizing radiation have divided clinicians as to the safety and appropriate use of the procedure. This article presents two differing viewpoints, one from a pair of orthopaedic surgeons who collectively have performed more than 300 radiosynovectomies in patients with haemophilia. They maintain that radiosynovectomy is a simple, effective, safe and low-cost technique children and adults with chronic haemophilic synovitis. The other perspective is from an experienced haemophilia treater who directs a major US haemophilia treatment centre. She believes that unresolved questions about the safety of radiation exposure in children argue against the use of radiosynovectomy in paediatric patients with haemophilia. “
“Summary.  Progress in the evidence-based care of haemophilia A and B worldwide has MTMR9 been historically challenged by the dearth of evaluable outcome data, including but not limited to the safety and effectiveness of therapeutic interventions. These challenges are partially rooted in the inherent difficulty of conducting prospective clinical trials and observational studies with statistically meaningful endpoints in a rare disease such as haemophilia. Despite the logistical barriers, the need for outcome data has never been more critical than in this time of expansive therapeutic advance tempered by the shrinking economic capacity to fund the rapidly increasing cost of treatment.

Included were 133 adult and paediatric patients with a high suspicion of VWD. Fifty-three were diagnosed with VWD: 47 (88.7%) with type 1 VWD, four (7.5%) with type 2a VWD and two (3.8%) with type 3 VWD. Mean age for

female patients was 19.5 years (range 3–44 years) and 18.5 years (range 4–63 years) for male patients. Mean age at start of bleeding symptoms was 8.8 years (range 1–61). The most frequent clinical symptoms were epistaxis (84.9%), ecchymosis (79.2%), haematomas (71.7%), gum bleeds (62.3%) and petechia (50.9%). Severe transoperative or postoperative bleeding was found in 17 patients (32.1%). Twenty-six women at childbearing age had a history of abnormal gynaecological bleeding. Our results clearly demonstrate the presence of VWD in Mexican and underscore the importance of a more detailed description of VWD. http://www.selleckchem.com/products/Lapatinib-Ditosylate.html Efforts to increase the awareness and diagnosis of VWD could help in better identification of patients with bleeding disorders and lead to early, appropriate management with safe and efficacious therapies such as desmopressin and

plasma concentrates. “
“Joint bleeding is the hallmark of severe haemophilia and the major cause of disability in patients with this coagulopathy. Repeated bleeding into the same Raf inhibitor joint can lead to chronic synovitis and progressive arthropathy. Radiosynovectomy is one option for the treatment of chronic haemophilic synovitis, but concerns about the risks of exposure

to ionizing radiation have divided clinicians as to the safety and appropriate use of the procedure. This article presents two differing viewpoints, one from a pair of orthopaedic surgeons who collectively have performed more than 300 radiosynovectomies in patients with haemophilia. They maintain that radiosynovectomy is a simple, effective, safe and low-cost technique children and adults with chronic haemophilic synovitis. The other perspective is from an experienced haemophilia treater who directs a major US haemophilia treatment centre. She believes that unresolved questions about the safety of radiation exposure in children argue against the use of radiosynovectomy in paediatric patients with haemophilia. “
“Summary.  Progress in the evidence-based care of haemophilia A and B worldwide has much been historically challenged by the dearth of evaluable outcome data, including but not limited to the safety and effectiveness of therapeutic interventions. These challenges are partially rooted in the inherent difficulty of conducting prospective clinical trials and observational studies with statistically meaningful endpoints in a rare disease such as haemophilia. Despite the logistical barriers, the need for outcome data has never been more critical than in this time of expansive therapeutic advance tempered by the shrinking economic capacity to fund the rapidly increasing cost of treatment.

9, 10 Functional ITPase prevents the incorporation of undesired purine base analogs into nucleic acids; this hydrolyzes them into monophosphates,

so their deleterious effects are avoided. Although the exact mechanisms of RBV-induced hemolytic anemia are still not fully understood, http://www.selleckchem.com/products/ch5424802.html these SNPs have already been identified as responsible for thiopurine analog toxicity and adverse sensitivity to purine base analog drugs.9, 11 Thus, the identified SNPs are excellent examples of important metabolic pathways that determine the effects and toxicities of different drugs. What might be the clinical consequences of these findings? We are certainly living in a very exciting time in which new disease-associated polymorphisms are being identified almost every day and are being published in the most prestigious

journals.12 These expensive and labor-extensive investigations are mainly performed for two reasons. The first aim is better risk prediction of a clinical phenotype in affected or treated patients; the second aim is the identification of key molecular pathways in the pathogenesis of the disease under investigation that might later lead to novel therapeutic options. In chronic HCV infection, the first aim has been put forward a lot in past years. In the near future, the following www.selleckchem.com/products/pexidartinib-plx3397.html scenario seems imaginable: in a given individual with chronic HCV infection and low baseline fibrosis,

we could genotype for the cirrhosis risk score and determine the likelihood of severe fibrosis developing. If this is the case, we will have a clear indication for antiviral therapy. As long as this is based on pegylated interferon and RBV, we will genotype for IL28B variants and determine PRKD3 the likelihood of a positive response to therapy. When IL28B wild-type alleles are found, there is a high chance of successful therapy, and we will continue genotyping for ITPA gene variants to determine the risk for RBV-induced hemolytic anemia. We can also test for gene polymorphisms that are associated with interferon-induced expression,13 and further variants for treatment side effects will certainly be identified. However, although this scenario might be advantageous for patients who are carriers of the low-risk alleles, the question of what happens with subjects with at-risk alleles of the SNPs arises. Would we really exclude patients with IL28B or ITPA risk variants from antiviral therapies? The answer is probably no. Therefore, the second aim of genome-wide association studies needs to be pushed further. Only when we have translated the genetic findings into new tailored therapies based on functional studies of the identified gene pathways will the era of personalized medicine in hepatitis C have been reached.

Among the validated targets, we chose the transcriptional repressor CUTL1 (also known as CDP [CCAAT displacement protein], Cut, or Cux-1)20 for PD-1/PD-L1 inhibitor review further investigation. Finally, we employed a lentiviral-mediated stable expression system to confirm the role of miR-122 in regulating hepatocyte proliferation and differentiation. In combination,

we placed miR-122 both upstream and downstream of the known gene regulatory network in liver development, which provides an exciting basis for understanding the regulation of liver development. In addition, our results also shed light on the cause and contribution of the down-regulation of miR-122 in HCCs. C/EBP, CCAAT/enhancer-binding protein; CTCF, CCCTC-binding factor; e, embryonic day; HCC, hepatocellular carcinoma; HNF, hepatocyte nuclear factor; LETF, liver-enriched transcription factor; MAP3K, mitogen-activated protein kinase kinase kinase; miR-122, microRNA-122; miRNA, microRNA; mRNA, messenger RNA; qRT-PCR, quantitative reverse-transcription polymerase chain reaction; SRF, serum response factor; UTR, untranslated region. Detailed materials and methods are described in the Supporting Information. Fetal, neonatal, and adult livers were isolated from C57BL/6J mice. Cell lines used were HepG2, Huh7, Sk-hep-1, SMMC-7721, and 293FT. miR-122 and control mimics were

synthesized by GenePharma (Shanghai, China). Anti-miR inhibitors for miR-122 and negative control were obtained from Ambion. All primary antibodies used for chromatin immunoprecipitation assays and western blot analyses of target genes were obtained from Santa Cruz Biotechnology. Quantitative eltoprazine reverse-transcription VX-809 nmr polymerase chain reaction (qRT-PCR) data are expressed as the mean ± standard deviation (SD) and luciferase data are presented as the mean + SD.

The differences between groups were analyzed using one-way analysis of variance, with P < 0.05 considered statistically significant (two-tailed). To search for regulators that might control in vivo transcription of miR-122, we focused primarily on the transcription factors that play important roles in regulating hepatocyte differentiation during liver development. Among the six families of liver-enriched transcription factors (LETFs) that have been characterized,18 several LETFs (including C/EBPα, HNF1α, HNF3α, HNF3β, and HNF3γ, and HNF4α,) are essential for expression of the complete repertoire of proteins that define hepatocyte function.21 C/EBPα, HNF1α HNF3β, and HNF4α, were further selected because they are highly abundant in both human and mouse liver (Supporting Fig. 1). We first investigated whether LETF expression correlated with miR-122 levels in both mouse embryonic livers and human HCC cell lines. The expression of miR-122 was detected by way of northern blot analysis and qRT-PCR. As shown in Fig. 1A,B, consistent with the previous report,11 miR-122 was gradually up-regulated in the fetal liver from e12.5 to birth.

Our findings reveal that dysregulation of miRNA-122 (miR-122) contributes to hepatic insulin resistance through PTP1B induction. Flavonoids are being actively studied BMN-673 as potential treatments for components of the metabolic syndrome. In our previous study, treatment with licorice flavonoid ameliorated liver steatosis.12 In the present study, we additionally discovered the effect of c-Jun

N-terminal kinase 1 (JNK1) inhibition by isoliquiritigenin (IsoLQ) or liquiritigenin (LQ) on miR-122 dysregulation using in vivo models and cell-based assays. Here, we report that they have the ability to abolish hepatic insulin resistance by recovering the constitutive expression of miR-122 responsible

for PTP1B down-regulation. Information on the materials used in this study is described in the Supporting Information. Animal studies were conducted in accordance with the guidelines of the Institutional Cabozantinib Animal Use and Care Committee. Male C57BL/6 mice at 6 weeks of age were started on a high-fat diet (HFD) for 11 weeks. Detailed information is provided in the Supporting Information. HepG2, H4IIE, C2C12, and 3T3-L1 cell lines were purchased from the American Type Culture Collection (ATCC, Rockville, MD). The isolation of primary rat hepatocytes is described in the Supporting Information. The plasmid containing Luc-PTP1B-3′UTR (3′-untranslated region; Product ID: HmiT015828-MT01) was specifically synthesized (GeneCopoeia, Rockville, MD) and was used in luciferase reporter assay. The plasmid contains firefly luciferase fused to the 3′UTR of human PTP1B, and Renilla luciferase that functions as a tracking gene. pMiR-122a luciferase reporter vector containing the firefly luciferase gene and miR-122 target site at 3′UTR was purchased from Signosis (Sunnyvale, CA). When

miR-122 is expressed, it binds to the sequence and results in repression of the luciferase gene. The sources of other vectors and procedures used in this study for transient transfections and reporter gene assays are provided in the Supporting Information. Total Glycogen branching enzyme RNA was extracted with TRIzol (Invitrogen, Carlsbad, CA) and was reverse-transcribed. Quantitative real-time PCR (qRT-PCR) was performed with the Light Cycler 1.5 (Roche, Mannheim, Germany). Chromatin immunoprecipitation assay was done using the EZ ChIP kit (Upstate Biotechnology, Lake Placid, NY) according to the manufacturer’s protocol. HFD feeding increased the mRNA and protein levels of PTP1B (Fig. 1A); the change in the level of PTP1B protein was greater than that in its mRNA, suggesting that a posttranscriptional mechanism might be involved in this event. RNA22 and TargetScan programs enabled us to select miRNAs that potentially bind to the 3′-untranslated region (3′UTR) of PTP1B (PTPN1) mRNA (Fig.

Our results are of further relevance considering that most patients with HCC are diagnosed at an advanced stage and that this group included the majority of patients

who were candidates for sorafenib treatment. By contrast, BCLC B patients who failed or were not suitable for locoregional treatments are a heterogeneous group of patients, representing a small subgroup of HCC patients who are candidates for sorafenib treatment, and not fully representative of the entire BCLC B spectrum. The robustness of these results was confirmed Buparlisib in the probabilistic sensitivity analysis, showing that the probability of dose-adjusted sorafenib providing a cost-effective alternative to BSC was about 70% for advanced and 10% for intermediate HCC at a willingness-to-pay threshold of €38,000 per QALY.

The cost-effectiveness of dose-adjusted sorafenib in both advanced and intermediate HCC was sensitive to the BSC survival rate, sorafenib treatment duration, and the choice of parametric model used to predict survival gain. It is important to highlight that dose-adjusted sorafenib remains cost-effective in BCLC C HCC patients under a wide range of survival of untreated patients. This issue is very relevant, given the high heterogeneity and the unpredictability BAY 57-1293 in vitro of clinical behavior of advanced HCC. 3 On the efficacy side of the cost equation, identification of robust predictive biomarkers would increase the overall efficacy of sorafenib for HCC by treating only those patients most likely to respond. This is not a trivial point, because sorafenib therapy is costly and still in search of optimization due to the lack of serum biomarkers of early response that are deemed necessary to generate Isotretinoin response-guided therapeutic algorithms. Moreover, the identification of stopping rules based on predictors of mortality (such as early radiologic progression)

could assist the clinician in the cost-effective management of patients with HCC. Unfortunately, stopping sorafenib in patients with early radiologic progression only marginally improves the cost-effectiveness ratio. Therefore, the identification of the optimal sorafenib dose, effective but not toxic, remains to date the only strategy to substantially improve the ICER. Modeling the indication for treatment of advanced/intermediate HCC with dose-adjusted sorafenib clearly improves its cost effectiveness. In this line, the role of dose-adjusted sorafenib should be taken into account also for the future perspectives in the adjuvant setting after resection/ablation or after transarterial chemoembolization and for the design of future comparative trials versus novel targeted therapies. Although the proposed algorithms are useful tools for decision making, the treatment strategy should be carefully agreed upon with the patient, taking into account all the different factors, particularly the safety profile, that can interfere with treatment response.

Our results are of further relevance considering that most patients with HCC are diagnosed at an advanced stage and that this group included the majority of patients

who were candidates for sorafenib treatment. By contrast, BCLC B patients who failed or were not suitable for locoregional treatments are a heterogeneous group of patients, representing a small subgroup of HCC patients who are candidates for sorafenib treatment, and not fully representative of the entire BCLC B spectrum. The robustness of these results was confirmed Pexidartinib in vitro in the probabilistic sensitivity analysis, showing that the probability of dose-adjusted sorafenib providing a cost-effective alternative to BSC was about 70% for advanced and 10% for intermediate HCC at a willingness-to-pay threshold of €38,000 per QALY.

The cost-effectiveness of dose-adjusted sorafenib in both advanced and intermediate HCC was sensitive to the BSC survival rate, sorafenib treatment duration, and the choice of parametric model used to predict survival gain. It is important to highlight that dose-adjusted sorafenib remains cost-effective in BCLC C HCC patients under a wide range of survival of untreated patients. This issue is very relevant, given the high heterogeneity and the unpredictability GSK1120212 chemical structure of clinical behavior of advanced HCC. 3 On the efficacy side of the cost equation, identification of robust predictive biomarkers would increase the overall efficacy of sorafenib for HCC by treating only those patients most likely to respond. This is not a trivial point, because sorafenib therapy is costly and still in search of optimization due to the lack of serum biomarkers of early response that are deemed necessary to generate CYTH4 response-guided therapeutic algorithms. Moreover, the identification of stopping rules based on predictors of mortality (such as early radiologic progression)

could assist the clinician in the cost-effective management of patients with HCC. Unfortunately, stopping sorafenib in patients with early radiologic progression only marginally improves the cost-effectiveness ratio. Therefore, the identification of the optimal sorafenib dose, effective but not toxic, remains to date the only strategy to substantially improve the ICER. Modeling the indication for treatment of advanced/intermediate HCC with dose-adjusted sorafenib clearly improves its cost effectiveness. In this line, the role of dose-adjusted sorafenib should be taken into account also for the future perspectives in the adjuvant setting after resection/ablation or after transarterial chemoembolization and for the design of future comparative trials versus novel targeted therapies. Although the proposed algorithms are useful tools for decision making, the treatment strategy should be carefully agreed upon with the patient, taking into account all the different factors, particularly the safety profile, that can interfere with treatment response.

Methods: From Jan 2007 to April 2009, a cross-sectional survey was conducted in a representative Chinese army population, which was selected from Plateau cold region and plain temperate using randomized, stratified, multistage sampling methodology. All respondents completed the Rome III Modular Questionnaire. The collected MK-2206 data were double input by EpiData3.02 software and analyzed by SPSS 13.0 software. Results: The overall prevalence of FGIDs in the army population of plateaus cold region (31.4%) was significantly higher than those in the plain temperate (25.04%), P < 0.05. IBS was one of the most

common FGIDs in the army population, whatever in plateau cold region (21.06%) or in plain temperate (13.02%). The higher prevalence of FGIDs in plateaus cold region included functional heartburn (9.80%), functional abdominal pain syndrome (4.94%) and functional constipation (4.58%), meanwhile functional dyspepsia (5.92%), functional constipation (5.49%)

and functional heartburn (3.32%) in the plain temperate. Conclusion: The overall prevalence of FGIDs in the army population of plateaus cold region was significantly higher than those in the plain temperate. IBS was the highest prevalence of FGIDs in the army population. selleck chemical Key Word(s): 1. G protein-coupled receptor kinase FGIDs; 2. Epidemiology; 3. Army; 4. Plateau and plain; Presenting Author: YUJEN FANG Additional Authors: JYHMING LIOU, CHIEHCHANG CHEN, JIYUH LEE, MEIJYH

CHEN, PINGHUEI TSENG, JAWTOWN LIN, HSIUPO WANG, MINGSHIANG WU Corresponding Author: MINGSHIANG WU Affiliations: National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan.; National Taiwan University Hospital, Taipei, Taiwan.; National Taiwan University Hospital, Taipei, Taiwan. Objective: Functional dyspepsia (FD) is a common heterogeneous disease, effect life quality and health care burden. The pathophysiology of FD remains to be elucidated. The recent Rome III criteria are implemented for diagnosis and further subtype classification, including epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). Investigation of risk factors based on new criteria in Asia is scant. We aim to study risk factors based on Rome III criteria and compare whether different factors exist in subgroups. Methods: From January, 2011 to May, 2012, consecutive dyspeptic outpatients were enrolled with Rome III diagnostic questionnaire, lifestyle and 5-item Brief Symptom Rating Scale (BSRS-5) in National Taiwan University Hospital and its Yuan-Lin Branch. All subjects underwent esophagoduodenoscopy and laboratory checkup to exclude organic or metabolic diseases.