Browsing by Author "Li H.-Y."

Background: Primary aldosteronism (PA) is a common curable disease of secondary hypertension. Most such patients have either idiopathic bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA). Bilateral APAs are reportedly extremely rare. Aim: To compare the distinctive characteristics, clinical course, and outcomes of bilateral APA vs. BAH. Design: Retrospective record review. Methods: From July 1994 to Jan 2007, 190 patients diagnosed with PA underwent surgical intervention at our hospital. Bilateral APA was diagnosed in 7/164 patients with histologically-proven APA. Twenty-one patients diagnosed as BAH, and 21 randomly selected of unilateral APA patients, matched by age and sex served as controls. Results: Patients with bilateral APA had similar blood pressure, arterial blood gas analysis, spot urinary potassium to creatinine ratio and clinical symptoms to those with BAH, but lower serum potassium levels (p = 0.027), lower plasma renin activity (p = 0.037), and higher plasma aldosterone concentrations (p = 0.029). Aldosterone-renin ratio (ARR) after administration of 50 mg captopril was higher in bilateral APA than in BAH patients (p = 0.023), but not different between unilateral APA and BAH (p = 0.218). A cut-off of ARR >100 ng/dl per ng/ml/h and plasma aldosterone >20 ng/dl after captopril significantly differentiated bilateral APA from BAH. Bilateral subtotal adrenalectomy normalized blood pressure and biochemistry in all patients with bilateral APA. Discussion: Bilateral APA, presenting simultaneously or sequentially, may not be a rare disease, accounting for 4.3> of APA in this sample. The clinical presentations of bilateral functional adenoma are not different from BAH, but patients with low serum potassium and ARR > 100 after captopril should be carefully evaluated for bilateral adenoma. ? 2008 The Authors.

A unique molecular library consisting of all sixteen synthetic ADMDP (1-aminodeoxy-DMDP) stereoisomers has been prepared and evaluated for inhibitory activity against α-Gal A, and ability to impart thermal stabilization of this enzyme. The results of this testing led us to develop a novel pharmacological chaperone for the treatment of Fabry disease. 3-Epimer ADMDP was found to be an effective pharmacological chaperone, able to rescue α-Gal A activity in the lymphoblast of the N215S Fabry patient-derived cell line, without impairment of cellular β-galactosidase activity. When 3-epimer ADMDP was administered with rh-α-Gal A (enzyme replacement therapy) for the treatment of Fabry patient-derived cell lines, improvements in the efficacy of rh-α-Gal A was observed, which suggests this small molecule can also provide clinical benefit of enzyme replacement therapy in Fabry disease. ? 2016

Background. Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection (BSI) are limited. Daptomycin, although not currently approved for this indication, is frequently used for the treatment of VRE-BSI. Its optimal dose still needs to be determined. Methods. We conducted a prospective, observational, cohort study during 2010-2015. We included patients who received a daptomycin dose of ?6 mg/kg for the treatment of VRE-BSI caused by daptomycin-susceptible VRE. The primary endpoint was 14-day mortality, and multivariable logistic regression was performed for outcome analysis. Results. We included 112 patients treated with daptomycin for VRE-BSI and with evaluable clinical outcomes. The daptomycin minimum inhibitory concentration (MIC) was 4 mg/L in 78 (69.6%) and ?2 mg/L in 34 (30.4%) isolates. The overall mortality was 40/112 (35.7%). The unadjusted mortality was 18/36 (50.0%) for a daptomycin dose of <7 mg/kg, 17/51 (33.3%) for a dose of 7-9 mg/kg, and 5/25 (20%) for a dose of ?9 mg/kg (P = .05). The best outcomes were associated with a daptomycin dose of ?9 mg/kg compared to doses of <7 mg/kg (adjusted odds ratio [aOR], 10.57; 95% confidence interval [CI], 2.25-49.62; P=.003) and 7-9 mg/kg (aOR, 5.01; 95% CI, 1.14-21.98; P=.03). There was no significant difference in mortality with respect to the daptomycin MIC. There was no association between daptomycin dose and elevated creatinine kinase. Conclusion. Higher daptomycin doses (?9 mg/kg) were associated with lower mortality in patients with VRE-BSI. Our results suggest that higher daptomycin doses need to be considered for VRE-BSI treatment. ? The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Systematic conservation planning (SCP) deals with a delicate interplay of competing interests and has far-reaching impacts for all stakeholders and systems involved. While SCP has traditionally attempted to conserve ecosystem services that benefit ecological systems, public perceptions of conservation initiatives influence their ultimate feasibility and sustainability. In an attempt to balance ecological integrity, social utility, and urban development, this study develops a framework that applies four popular models to represent these competing factors, including two ecosystem services models-InVEST (Integrated Valuation of Environmental Services and Tradeoffs) for biophysical services (BpS), and SolVES (Social Values for Ecosystem Services) for social values (SV); a land use and land cover (LULC) suitability model; and Zonation for delimiting high priority areas. We also analyze a number of conservation scenarios that consider varying levels of urban development. While BpS are distributed with considerable spatial variability, SV spatially overlap. Approximately 6% of the area was identified as having both high BpS and SV, whereas a further 24.5% of the area was identified as either high BpS low SV or vise-versa. Urban development scenarios affected the conservation area selection drastically. These results indicate tradeoffs and potential synergies between development, SV, and BpS. Our findings suggest that the information provided by the proposed framework can assist in finding solutions to social-ecological planning complexities that serve multiple stakeholders. © 2017 by the authors.

Objective: To examine the safety and efficacy of laparoscopic adrenalectomy with needlescopic instruments for most adrenal tumors less than 5 cm. Methods: Transperitoneal laparoscopic adrenalectomy with needlescopic instruments for 112 patients with presumptively benign adrenal tumors < 5 cm were enrolled from July 2000 to February 2005. Operative time, blood loss, conversion and complication rates, and postoperative data were analyzed by appropriate statistical methods. Results: All 112 operations were completed without any mortality or reoperation. Mean operative time was 151 min and mean blood loss was 30 ml. Only one patient required a blood transfusion and application of a hand-assisted device. Conversion to conventional laparoscopic instruments was necessary in another five patients (4.5%). The operative time of the latter 100 cases (147 ± 5.1 min, mean ± standard error of mean) was significantly shorter than that of the initial 12 cases (183 ± 8.8 min, p = 0.001). Larger tumors, previous abdominal surgery, and pheochromocytoma group were independent risk factors of a longer operative time. Except for one leiomyosarcoma, all other tumors were benign adrenal pathologies (57 aldosterone-producing adenomas, 23 Cushing's adenomas, 12 pheochromocytomas, and 20 incidentalomas). Conclusion: The safety and effectiveness of laparoscopic adrenalectomy employing needlescopic instruments for most adrenal tumors less than 5 cm was feasible with acceptable operative time. Pheochromocytomas can also be managed with a longer operative time. Patients with previous upper midline or ipsilateral upper quadrant open surgery might not be suitable candidates for such a technique. ? 2007 European Association of Urology.

Triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. The major sites for TNBC metastasis include the lungs, brain, liver, and bone. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides and have been reported as important regulators in BC metastasis. However, the underlying mechanisms for lncRNAs regulating TNBC metastasis are not fully understood. Here we found that linc-ZNF469-3 was highly expressed in lung-metastatic LM2-4175 TNBC cells and overexpression of linc-ZNF469-3 enhanced invasion ability and stemness properties in vitro and lung metastasis in vivo. Furthermore, we found linc-ZNF469-3 physically interacted with miR-574-5p and overexpression of miR-574-5p attenuated ZEB1 expression. Importantly, endogenous high expressions of linc-ZNF469-3 and ZEB1 were correlated with tumor recurrence in TNBC patients with lung metastasis. Taken together, our findings suggested that linc-ZNF469-3 promotes lung metastasis of TNBC through miR-574-5p-ZEB1 signaling axis and may be used as potential prognostic marker for TNBC patients. ? 2018, Macmillan Publishers Limited, part of Springer Nature.

A kinesin family member 5b (KIF5B)-MET proto-oncogene, receptor tyrosine kinase (MET) rearrangement was reported in patients with lung adenocarcinoma but its oncogenic function was not fully evaluated. We used one-step reverse transcription-polymerase chain reaction for RNA samples to screen for the KIF5B-MET fusion in 206 lung adenocarcinoma and 28 pulmonary sarcomatoid carcinoma patients. Genomic breakpoints of KIF5B-MET were determined by targeted next-generation sequencing. Soft agar colony formation assays, proliferation assays, and a xenograft mouse model were used to investigate its oncogenic activity. In addition, specific MET inhibitors were administered to evaluate their anti-tumor activities. A KIF5B-MET fusion variant in a patient with a mixed-type adenocarcinoma and sarcomatoid tumor was identified, and another case was found in a pulmonary sarcomatoid carcinoma patient. Both cases carried the same chimeric gene, a fusion between exons 1–24 of KIF5B and exons 15–21 of MET. KIF5B-MET-overexpressing cells exhibited significantly increased proliferation and colony-forming ability. Xenograft tumors harboring the fusion gene demonstrated significantly elevated tumor growth. Ectopic expression of the fusion gene stimulated the phosphorylation of KIF5B-MET as well as downstream STAT3, AKT, and ERK1/2 signaling pathways. The MET inhibitors significantly repressed cell proliferation; phosphorylation of downstream STAT3, AKT, and ERK1/2; and xenograft tumorigenicity. In conclusion, the KIF5B-MET variant was demonstrated to have an oncogenic function in cancer cells. These findings have immediate clinical implications for the targeted therapy of subgroups of non-small cell lung cancer patients. ? 2018 The Authors

Objective: To test the application of a target enrichment next-generation sequencing (NGS) jaundice panel in genetic diagnosis of pediatric liver diseases. Study design: We developed a capture-based target enrichment NGS jaundice panel containing 42 known disease-causing genes associated with jaundice or cholestasis and 10 pathway-related genes. During 2015-2017, 102 pediatric patients with various forms of cholestasis or idiopathic liver diseases were tested, including patients with initial diagnosis of cholestasis in infancy, progressive familial intrahepatic cholestasis, syndromic cholestasis, Wilson disease, and others. Results: Of the 102 patients, 137 mutations/variants in 44 different genes were identified in 84 patients. The genetic disease diagnosis rate was 33 of 102 (32.4%). A total of 79 of 102 (77.5%) of patients had at least 1 heterozygous genetic variation. Those with progressive intrahepatic cholestasis or syndromic cholestasis in infancy had a diagnostic rate of 62.5%. Disease-causing mutations, including ATP8B1, ABCB11, ABCB4, ABCC2, TJP2, NR1H4 (FXR), JAG1, AKR1D1, CYP7B1, PKHD1, ATP7B, and SLC25A13, were identified. Nine patients had unpredicted genetic diagnosis with atypical phenotype or novel mutations in the investigational genes. We propose an NGS diagnosis classification categorizing patients into high (n = 24), moderate (n = 9), or weak (n = 25) levels of genotype–phenotype correlations to facilitate patient management. Conclusions: This panel enabled high-throughput detection of genetic variants and disease diagnosis in patients with a long list of candidate causative genes. A NGS report with diagnosis classification may aid clinicians in data interpretation and patient management. ? 2018 Elsevier Inc.