Hsin chu Mackay Memorial Hospital

Hsinchu, Taiwan

Hsin chu Mackay Memorial Hospital

Hsinchu, Taiwan

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Hsieh J.-Y.,National Yang Ming University | Wang H.-W.,National Yang Ming University | Wang H.-W.,Taipei Medical University Hospital | Chang S.-J.,Hsin Chu Mackay Memorial Hospital | And 8 more authors.
PLoS ONE | Year: 2013

Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases such as infarcted myocardia and strokes because of their ability to promote endogenous angiogenesis and neurogenesis via a variety of secreted factors. MSCs found in the Wharton's jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. We isolated MSCs from Wharton's jelly and bone marrow (WJ-MSCs and BM-MSCs, respectively) and compared their secretomes. It was found that WJ-MSCs expressed more genes, especially secreted factors, involved in angiogenesis and neurogenesis. Functional validation showed that WJ-MSCs induced better neural differentiation and neural cell migration via a paracrine mechanism. Moreover, WJ-MSCs afforded better neuroprotection efficacy because they preferentially enhanced neuronal growth and reduced cell apoptotic death of primary cortical cells in an oxygen-glucose deprivation (OGD) culture model that mimics the acute ischemic stroke situation in humans. In terms of angiogenesis, WJ-MSCs induced better microvasculature formation and cell migration on co-cultured endothelial cells. Our results suggest that WJ-MSC, because of a unique secretome, is a better MSC source to promote in vivo neurorestoration and endothelium repair. This study provides a basis for the development of cell-based therapy and carrying out of follow-up mechanistic studies related to MSC biology. © 2013 Hsieh et al.


Liao Y.-Y.,National Tsing Hua University | Liao Y.-Y.,Hungkuang University | Lee W.-N.,University of Hong Kong | Lee M.-R.,National Tsing Hua University | And 5 more authors.
Radiology | Year: 2015

Purpose: To determine the feasibility of two-dimensional (2D) ultrasonographic (US) strain imaging for quantifying and mapping mechanical behaviors of the median nerve, flexor retinaculum, and flexor tendons within the carpal tunnel in normal and carpal tunnel syndrome (CTS) disease states during active finger motion. Materials and Methods: This prospective study was approved by the institutional review board; all subjects gave written informed consent and had both of their hands examined. Ten wrists in 10 healthy volunteers (age range, 35-51 years) and 16 wrists in 12 patients with CTS (age range, 37-55 years) were examined. In the patients, CTS had been confirmed on the basis of clinical symptoms and results of electrophysiologic studies. Raw US signals were acquired and were cross correlated to enable estimation of 2D incremental displacements, from which 2D strains were computed. The median nerve was characterized by the axial normal strain, while the flexor tendons and the flexor retinaculum were characterized by the shear strain. Temporal mean values (mean cumulative strain [MCS] values) and standard deviations (standard deviations of the cumulative strain [SDCS]) of the spatially averaged cumulative strains in each tissue region over the entire cycle of finger motion were compared by using an unpaired two-tailed Student t test. Results: MCS for patients with CTS and volunteers was similar. The SDCS for the shear strain of the flexor retinaculum was significantly lower (P <.001) in patients with CTS than in healthy volunteers, while that for the axial strain of the median nerve was higher in healthy volunteers than in patients with CTS (P =.0065). Conclusion: US strain imaging can be used to quantify and map tissue kinematics in the carpal tunnel and to differentiate abnormal from normal median nerves in the wrist. © RSNA, 2015.


Yang C.Y.,Hsin Chu Mackay Memorial Hospital | Wang C.P.,National Taiwan University | Wang C.P.,National Taiwan University Hospital
Journal of Medical Ultrasound | Year: 2014

Temporomandibular joint (TMJ) tumors may initially present with symptoms similar to TMJ internal derangements and myositis of masticatory muscles. However, malignant tumors and specific types of benign tumors, such as giant cell tumors, may need aggressive surgical intervention. The current case is a 41-year-old man who initially presented with right preauricular pain. Computed tomography (CT) revealed a destructive bone lesion over the right TMJ with temporal bone destruction. A biopsy conducted with an ultrasound-guided core needle confirmed that the lesion was a giant cell tumor. Giant cell tumors can eventually destroy the surrounding tissue. Magnetic resonance imaging and CT have been traditionally used to evaluate TMJ disorders, whereas ultrasonography provides real-time imaging for evaluating the joint structure, movement, and biopsy guidance. For a TMJ tumor, a precise diagnosis is necessary for adequate planning of treatment. Ultrasound-guided core needle biopsy is a safe and effective method for confirming a diagnosis. © 2014.


Wang H.-W.,National Yang Ming University | Wang H.-W.,Taipei Medical University Hospital | Huang T.-S.,National Yang Ming University | Lo H.-H.,National Yang Ming University | And 14 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2014

Objective-Defects in angiogenesis/vasculogenesis or vessel repair are major complications of coronary artery disease (CAD). Endothelial progenitor cells (EPCs) play a fundamental role in postnatal vascular repair and CAD. The role of microRNAs in CAD pathogenesis and their potential as biomarkers remain to be elucidated. Approach and results-MicroRNA-31 (miR-31) level in both the plasma and EPCs of patients with CAD is found lower. miR-31 regulates EPC activities by targeting FAT atypical cadherin 4 and thromboxane A2 receptor, which show increased expression in CAD EPCs. Overexpressing miR-31 in CAD EPCs rescued their angiogenic and vasculogenic abilities both in vitro and in vivo. When exploring approaches to restore endogenous miR-31, we found that far-infrared treatment enhanced the expression of not only miR-31, but also miR-720 in CAD EPCs. miR-720, which was also decreased in EPCs and the plasma of patients with CAD, stimulated EPC activity by targeting vasohibin 1. The miR720-vasohibin 1 pair was shown to be downstream of FAT atypical cadherin 4, but not of thromboxane A2 receptor. FAT atypical cadherin 4 inhibited miR-720 expression via repression of the planar cell polarity signaling gene four-jointed box 1 (FJX1), which was required for miR-720 expression through a hypoxia-inducible factor 1, α subunit-dependent mechanism. Restoring miR-720 level strengthened activity of CAD EPCs. The miR-31-miR-720 pathway is shown critical to EPC activation and that downregulation of this pathway contributes to CAD pathogenesis. Circulating levels of miR-31, miR-720, and vasohibin 1 have the potential to allow early diagnosis of CAD and to act as prognosis biomarkers for CAD and other EPC-related diseases. Conclusions-Manipulating the expression of the miR-31-miR-720 pathway in malfunction EPCs should help develop novel therapeutic modalities. © 2014 American Heart Association, Inc.


Wang H.-W.,National Yang Ming University | Wang H.-W.,Taipei Medical University Hospital | Lo H.-H.,National Yang Ming University | Chiu Y.-L.,National Yang Ming University | And 9 more authors.
PLoS ONE | Year: 2014

Dysfunction and reduction of circulating endothelial progenitor cell (EPC) is correlated with the onset of cardiovascular disorders including coronary artery disease (CAD). VEGF is a known mitogen for EPC to migrate out of bone marrow to possess angiogenic activities, and the plasma levels of VEGF are inversely correlated to the progression of CAD. Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. However, how miRNAs and VEGF cooperate to regulate CAD progression is still unclear. Through the small RNA sequencing (smRNA-seq), we deciphered the miRNome patterns of EPCs with different angiogenic activities, hypothesizing that miRNAs targeting VEGF must be more abundant in EPCs with lower angiogenic activities. Candidates of anti-VEGF miRNAs, including miR-361-5p and miR-484, were enriched in not only diseased EPCs but also the plasma of CAD patients. However, we found out only miR-361-5p, but not miR-484, was able to suppress VEGF expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-361-5p to the 3′-UTR of VEGF mRNA. Knock down of miR-361-5p not only restored VEGF levels and angiogenic activities of diseased EPCs in vitro, but further promoted blood flow recovery in ischemic limbs of mice. Collectively, we discovered a miR-361-5p/VEGF-dependent regulation that could help to develop new therapeutic modalities not only for ischemia-related diseases but also for tumor angiogenesis. © 2014 Wang et al.


PubMed | Taipei Medical University Hospital, Hsin Chu Mackay Memorial Hospital, National Yang Ming University and Taipei Veterans General Hospital
Type: | Journal: BMC medical genomics | Year: 2015

Pediatric embryonal brain tumors (PEBTs), which encompass medulloblastoma (MB), primitive neuroectodermal tumor (PNET) and atypical teratoid/rhabdoid tumor (AT/RT), are the second most prevalent pediatric brain tumor type. AT/RT is highly malignant and is often misdiagnosed as MB or PNET. The distinction of AT/RT from PNET/MB is of clinical significance because the survival rate of patients with AT/RT is substantially lower. The diagnosis of AT/RT relies primarily on morphologic assessment and immunohistochemical (IHC) staining for a few known markers such as the lack of INI1 protein expression. However, in our clinical practice we have observed several AT/RT-like tumors, that fulfilled histopathological and all other biomarker criteria for a diagnosis of AT/RT, yet retained INI1 immunoreactivity. Recent studies have also reported preserved INI1 immunoreactivity among certain diagnosed AT/RTs. It is therefore necessary to re-evaluate INI1(+), AT/RT-like cases.Sanger sequencing, array CGH and mRNA microarray analyses were performed on PEBT samples to investigate their genomic landscapes.Patients with AT/RT and those with INI(+) AT/RT-like tumors showed a similar survival rate, and global array CGH analysis and INI1 gene sequencing showed no differential chromosomal aberration markers between INI1(-) AT/RT and INI(+) AT/RT-like cases. We did not misdiagnose MBs or PNETs as AT/RT-like tumors because transcriptome profiling revealed that not only did AT/RT and INI(+) AT/RT-like cases express distinct mRNA and microRNA profiles, their gene expression patterns were different from those of MBs and PNETs. The most similar transcriptome profile to that of AT/RTs was the profile of embryonic stem cells. However; the transcriptome profile of INI1(+) AT/RT-like tumors was more similar to that of somatic neural stem cells, while the profile of MBs was closer to that of fetal brain tissue. Novel biomarkers were identified that can be used to distinguish INI1(-) AT/RTs, INI1(+) AT/RT-like cases and MBs.Our studies revealed a novel INI1(+) ATRT-like subtype among Taiwanese pediatric patients. New diagnostic biomarkers, as well as new therapeutic tactics, can be developed according to the transcriptome data that were unveiled in this work.


Hsieh J.-Y.,National Yang Ming University | Fu Y.-S.,National Yang Ming University | Fu Y.-S.,Taipei Medical University Hospital | Chang S.-J.,Hsin Chu Mackay Memorial Hospital | And 3 more authors.
Stem Cells and Development | Year: 2010

Mesenchymal stem cells (MSCs) found in bone marrow (BM)-MSCs are an attractive source for the regeneration of damaged tissues. Alternative postnatal, perinatal, and fetal sources of MSCs are also under intensive investigation. MSCs from the Wharton's jelly matrix of umbilical cord (WJ)-MSCs have higher pancreatic and endothelial differentiation potentials than BM-MSCs, but the underlying mechanisms are poorly understood. We compared the gene expression profiles, enriched canonical pathways, and genetic networks of BM-MSCs and WJ-MSCs. WJ-MSCs express more angiogenesis-and growth-related genes including epidermal growth factor and FLT1, whereas BM-MSCs express more osteogenic genes such as RUNX2, DLX5, and NPR3. The gene expression pattern of BM-MSCs is more similar to osteoblasts than WJ-MSCs, suggesting a better osteogenic potential. In contrast, WJ-MSCs are more primitive because they share more common genes with embryonic stem cells. BM-MSCs are more sensitive to environmental stimulations because their molecular signatures altered more significantly in different culture conditions. WJ-MSCs express genes enriched in vascular endothelial growth factor and PI3K-NFκB canonical pathways, whereas BM-MSCs express genes involved in antigen presentation and chemokine/cytokine pathways. Drylab results could be verified by wetlab experiments, in which BM-MSCs were more efficient in osteogenic and adipogenic differentiation, whereas WJ-MSCs proliferated better. WJ-MSCs thus constitute a promising option for angiogenesis, whereas BM-MSCs in bone remodeling. Our results reveal systematically the underlying genes and regulatory networks of 2 MSCs from unique ontological and anatomical origins, as well as the resulted phenotypes, thereby providing a better basis for cell-based therapy and the following mechanistic studies on MSC biology. © 2010, Mary Ann Liebert, Inc.


Yang C.Y.,Hsin Chu MacKay Memorial Hospital | Yang C.-C.,MacKay Memorial Hospital | Yang C.-C.,MacKay Medical College
Acta Oto-Laryngologica | Year: 2015

Conclusion: The location of the foreign body did not correspond well to the location of pain reported by patients. When patients present with foreign bodies in the pharynx, in addition to recording the location of pain and foreign body sensation, clinicians should perform a comprehensive and thorough oropharyngeal examination to avoid misdiagnosis. Objectives: Physicians are often guided by patient-indicated locations of pharyngeal foreign bodies. In this study, we aimed to determine the correlation between the location of the subjective neck pain or foreign body sensation and the true location of the foreign body. Methods: We prospectively studied 90 patients who had pharyngeal foreign bodies removed at MacKay Memorial Hospital. We divided the head and neck into 10 zones according to the superficial anatomy. Subjective location, examination findings, and actual foreign body location were recorded and compared. Results: The overall subjective and true locations of the foreign body were poorly correlated (kappa 0.27, p = 0.003). The positive predictive value (PPV) for the midline neck was 68%, which was higher than that on either lateral side of the neck. PPV above cricoid cartilage level was 66%. © 2015 Informa Healthcare.


Liao Y.-Y.,National Tsing Hua University | Wu C.-C.,National Tsing Hua University | Kuo T.-T.,National Tsing Hua University | Kuo T.-T.,Hsin chu Mackay Memorial Hospital | And 3 more authors.
Medical Physics | Year: 2012

Purpose: Carpal tunnel syndrome (CTS) is the common entrapment neuropathy that occurs due to compression of the median nerve at the wrist. Ultrasound images have been used to highlight anatomical variants of the median nerve, and CTS is thought to be associated to enlargement of the cross-sectional area (CSA) of the median nerve. However, there remains controversy regarding the most appropriate cutoff values of the computer measurements including the CSA, flattening ratio, and palmar bowing of median nerve, especially given that they can be influenced by image artifacts and factors that differ between individual patients. This study proposed a modified ultrasound compound imaging technique by moving fingers to reduce image artifacts, and the estimates of the normalized CSA i.e., CSA at the wrist (CSAw) to CSA at the midforearm with the aim of reducing discrepancies in CSA estimates and improving the ability of CTS discrimination. Methods: The subjects were examined with their arms supine and while they were making repetitive movements of their fingers (from an open palm into a clenched fist) within 3 s. By a commercial ultrasound scanner with a 10-MHz linear array transducer, a total of 70 images were acquired in each subject. The frame rate of ultrasound system was 25 fps. Nine frames in the acquisition sequence that had produced partial speckle decorrelation were incoherently added to form a compound image, and the inplane motion of them was corrected using the multilevel block-sum pyramid algorithm. The manual contours outlined by ten experimenters and three physicians were used to test the performance in determining the boundary of the median nerve. The receiver operating characteristic (ROC) curve was used to evaluate the usefulness of the estimates in distinguishing healthy volunteers from CTS patients. Results: The manual contours of the median nerve in the compound images had an average area overlap exceeding 90 and relatively small area errors. The areas under the ROC curve obtained using the CSAw estimates for the original and compound images were 0.60 ± 0.09 (mean ± standard error) and 0.80 ± 0.05, respectively; that using normalized CSA estimates for the original and compound images were 0.76 ± 0.04 and 0.89 ± 0.04, respectively. The results show that variations in the CSAw values of compound images for healthy overweight and obese subjects can adversely influence CTS diagnosis, but that this can be overcome using the normalized CSA estimate of compound images. Conclusions: Compound imaging provides images of superior quality for determining the location of the median nerve boundary. Using the normalized CSA estimate would assist in eliminating problems associated with variability between populations, since the subject becomes his or her own internal control, thereby improving the ultrasound-based diagnosis of CTS. © 2012 American Association of Physicists in Medicine.


PubMed | Hsin Chu MacKay Memorial Hospital
Type: Journal Article | Journal: Acta oto-laryngologica | Year: 2015

The location of the foreign body did not correspond well to the location of pain reported by patients. When patients present with foreign bodies in the pharynx, in addition to recording the location of pain and foreign body sensation, clinicians should perform a comprehensive and thorough oropharyngeal examination to avoid misdiagnosis.Physicians are often guided by patient-indicated locations of pharyngeal foreign bodies. In this study, we aimed to determine the correlation between the location of the subjective neck pain or foreign body sensation and the true location of the foreign body.We prospectively studied 90 patients who had pharyngeal foreign bodies removed at MacKay Memorial Hospital. We divided the head and neck into 10 zones according to the superficial anatomy. Subjective location, examination findings, and actual foreign body location were recorded and compared.The overall subjective and true locations of the foreign body were poorly correlated (kappa 0.27, p = 0.003). The positive predictive value (PPV) for the midline neck was 68%, which was higher than that on either lateral side of the neck. PPV above cricoid cartilage level was 66%.

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