Validation of Pharyngeal Acid Reflux Episodes Using Hypopharyngeal Multichannel Intraluminal Impedance-pH

Yen-Yang Chen,Chen-Chi Wang,Ying-Cheng Lin,John Y Kao,Chun-Yi Chuang,Yung-An Tsou,Ja-Chih Fu,Sheng-Shun Yang,Chi-Sen Chang,Han-Chung Lien 대한소화기 기능성질환∙운동학회 2023 Journal of Neurogastroenterology and Motility (JNM Vol.29 No.1

Background/AimsHypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility. MethodsWe conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed. ResultsA total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%. ConclusionOur preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

Survival Benefit of Tamoxifen in Estrogen Receptor-Negative and Progesterone Receptor-Positive Low Grade Breast Cancer Patients

Li-Heng Yang,Hsin-Shun Tseng,Che Lin,Li-Sheng Chen,Shou-Tung Chen,Shou-Jen Kuo,Dar-Ren Chen 한국유방암학회 2012 Journal of breast cancer Vol.15 No.3

Purpose: This study aimed to analyze the efficacy and prognostic significance of adjuvant tamoxifen in breast cancer patients with various hormone receptor statuses. Methods: Typically, 1,260 female breast cancer patients were recruited in this study. The correlation between estrogen receptor (ER)/progesterone receptor (PR) phenotypes and clinical characteristics was investigated, and the survival rate was assessed after 5-year follow-up. Results: The 5-year overall survival (85%) was better in women under the age of 50 years. Patients with ER+/PR+ tumors had a better 5-year survival rate (94%); those with ER-/PR- tumors experienced the worst outcome (74% survival rate); whereas singlepositive cases were in between. In 97 out of 128 patients with ER-/PR+ tumors, tamoxifen was given as adjuvant hormonal therapy, and it increased the survival benefit in the lower grade group in terms of overall survival and disease-free survival (p=0.01 and p=0.03, respectively). Conclusion: For high-grade tumors with ER-/PR+, adjuvant tamoxifen therapy may have no survival benefit, whereas for the patients with low-grade ER-/PR+ tumors, adjuvant tamoxifen therapy is highly suggestive.

Strength failure behavior of granite containing two holes under Brazilian test

Huang, Yan-Hua,Yang, Sheng-Qi,Zhang, Chun-Shun Techno-Press 2017 Geomechanics & engineering Vol.12 No.6

A series of Brazilian tests under diameter compression for disc specimens was carried out to investigate the strength and failure behavior by using acoustic emission (AE) and photography monitoring technique. On the basis of experimental results, load-displacement curves, AE counts, real-time crack evolution process, failure modes and strength property of granite specimens containing two pre-existing holes were analyzed in detail. Two typical types of load-displacement curves are identified, i.e., sudden instability (type I) and progressive failure (type II). In accordance with the two types of load-displacement curves, the AE events also have different responses. The present experiments on disc specimens containing two pre-existing holes under Brazilian test reveal four distinct failure modes, including diametrical splitting failure mode (mode I), one crack coalescence failure mode (mode II), two crack coalescences failure mode (mode III) and no crack coalescence failure mode (mode IV). Compared with intact granite specimen, the disc specimen containing two holes fails with lower strength, which is closely related to the bridge angle. The failure strength of pre-holed specimen first decreases and then increases with the bridge angle. Finally, a preliminary interpretation was proposed to explain the strength evolution law of granite specimen containing two holes based on the microscopic observation of fracture plane.

Tumor-Suppression Mechanisms of Protein Tyrosine Phosphatase O and Clinical Applications

Kang, Man-Man,Shan, Shun-Lin,Wen, Xu-Yang,Shan, Hu-Sheng,Wang, Zheng-Jun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumor-suppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.

Distal Mean Nocturnal Baseline Impedance Predicts Pathological Reflux of Isolated Laryngopharyngeal Reflux Symptoms

Hua-Nong Luo,Chen-Chi Wang,Ying-Cheng Lin,Chun-Yi Chuang,Yung-An Tsou,Ja-Chih Fu,Sheng-Shun Yang,Chi-Sen Chang,Han-Chung Lien 대한소화기 기능성질환∙운동학회 2023 Journal of Neurogastroenterology and Motility (JNM Vol.29 No.2

Background/AimsDiagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS. MethodsIn this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured. ResultsDistal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH– (ILPRS in pH+ vs pH–: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH–: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH– subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH– subgroup and healthy controls (P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001). ConclusionDistal esophageal MNBI predicts pathological reflux in patients with ILPRS.

Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients

Jinlin Hou,Edward Gane,Rozalina Balabanska,Wenhong Zhang,Jiming Zhang,Tien Huey Lim,Qing Xie,Chau-Ting Yeh,Sheng-Shun Yang,Xieer Liang,Piyawat Komolmit,Apinya Leerapun,Zenghui Xue,Ethan Chen,Yuchen Zh 대한간학회 2024 Clinical and Molecular Hepatology(대한간학회지) Vol.30 No.2

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions: 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.