Cerebral Microbleeds in Autosomal Dominant Polycystic Kidney Disease

Li-Kai Tsai,Pei-Lung Chen,Hsin-Hsi Tsai,Ya-Fang Chen,Ping-Chun Wu,Jiann-Shing Jeng,Jenq-Wen Huang,Tzong-Shinn Chu,Juliana Tze-Wah Kao 대한뇌졸중학회 2020 Journal of stroke Vol.22 No.1

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Upregulating sirtuin 6 ameliorates glycolysis, EMT and distant metastasis of pancreatic adenocarcinoma with krüppel-like factor 10 deficiency

Tsai Yi-Chih,Chen Su-Liang,Peng Shu-Ling,Tsai Ya-Li,Chang Zuong-Ming,Chang Vincent Hung-Shu,Ch’ang Hui-Ju 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

Krüppel-like factor 10 (KLF10) is a tumor suppressor in multiple cancers. In a murine model of spontaneous pancreatic adenocarcinoma (PDAC), additional KLF10 depletion accelerated distant metastasis. However, Klf10 knockout mice, which suffer from metabolic disorders, do not develop malignancy. The mechanisms of KLF10 in PDAC progression deserve further exploration. KLF10-depleted and KLF10-overexpressing PDAC cells were established to measure epithelial-mesenchymal transition (EMT), glycolysis, and migration ability. A murine model was established to evaluate the benefit of genetic or pharmacological manipulation in KLF10-depleted PDAC cells (PDACshKLF10). Correlations of KLF10 deficiency with rapid metastasis, elevated EMT, and glycolysis were demonstrated in resected PDAC tissues, in vitro assays, and murine models. We identified sirtuin 6 (SIRT6) as an essential mediator of KLF10 that modulates EMT and glucose homeostasis. Overexpressing SIRT6 reversed the migratory and glycolytic phenotypes of PDACshKLF10 cells. Linoleic acid, a polyunsaturated essential fatty acid, upregulated SIRT6 and prolonged the survival of mice injected with PDACshKLF10. Modulating HIF1α and NFκB revealed that EMT and glycolysis in PDAC cells were coordinately regulated upstream by KLF10/SIRT6 signaling. Our study demonstrated a novel KLF10/SIRT6 pathway that modulated EMT and glycolysis coordinately via NFκB and HIF1α. Activation of KLF10/SIRT6 signaling ameliorated the distant progression of PDAC. Clinical Trial Registration: ClinicalTrials.gov. identifier: NCT01666184.

Numerical simulation of 2-D fluid-structure interaction with a tightly coupled solver and establishment of the mooring model

Tsai I-Chen,Li Sing-Ya,Hsiao Shih-Chun,Yu Hsiao 대한조선학회 2021 International Journal of Naval Architecture and Oc Vol.13 No.1

In this study, a newly enhanced Fluid-Structure Interaction (FSI) model which incorporates mooring lines was used to simulate a floating structure. The model has two parts: a Computational Fluid Dynamics (CFD) model and a mooring model. The open-source CFD OpenFOAM® v1712 toolbox was used in the present study, and the convergence criteria and relaxation method were added to the computational procedure used for the OpenFOAM multiphase flow solver, interDyMFoam. A newly enhanced, tightly coupled solver, CoupledinterDyMFoam, was used to decrease the artificial added mass effect, and the results were validated through a series of benchmark cases. The mooring model, based on the finite element method, was established in MATLAB® and was validated against a benchmark analytical elastic catenary solution and numerical results. Finally, a model which simulates a floating structure with mooring lines was successfully constructed by connecting the mooring model to CoupledinterDyMFoam.

An update of preimplantation genetic diagnosis in gene diseases, chromosomal translocation, and aneuploidy screening

Chang, Li-Jung,Chen, Shee-Uan,Tsai, Yi-Yi,Hung, Chia-Cheng,Fang, Mei-Ya,Su, Yi-Ning,Yang, Yu-Shih The Korean Society for Reproductive Medicine 2011 Clinical and Experimental Reproductive Medicine Vol.38 No.3

Preimplantation genetic diagnosis (PGD) is gradually widely used in prevention of gene diseases and chromosomal abnormalities. Much improvement has been achieved in biopsy technique and molecular diagnosis. Blastocyst biopsy can increase diagnostic accuracy and reduce allele dropout. It is cost-effective and currently plays an important role. Whole genome amplification permits subsequent individual detection of multiple gene loci and screening all 23 pairs of chromosomes. For PGD of chromosomal translocation, fluorescence $in-situ$ hybridization (FISH) is traditionally used, but with technical difficulty. Array comparative genomic hybridization (CGH) can detect translocation and 23 pairs of chromosomes that may replace FISH. Single nucleotide polymorphisms array with haplotyping can further distinguish between normal chromosomes and balanced translocation. PGD may shorten time to conceive and reduce miscarriage for patients with chromosomal translocation. PGD has a potential value for mitochondrial diseases. Preimplantation genetic haplotyping has been applied for unknown mutation sites of single gene disease. Preimplantation genetic screening (PGS) using limited FISH probes in the cleavage-stage embryo did not increase live birth rates for patients with advanced maternal age, unexplained recurrent abortions, and repeated implantation failure. Polar body and blastocyst biopsy may circumvent the problem of mosaicism. PGS using blastocyst biopsy and array CGH is encouraging and merit further studies. Cryopreservation of biopsied blastocysts instead of fresh transfer permits sufficient time for transportation and genetic analysis. Cryopreservation of embryos may avoid ovarian hyperstimulation syndrome and possible suboptimal endometrium.

Cerebral Venous Reflux and Dilated Basal Ganglia Perivascular Space in Hypertensive Intracerebral Hemorrhage

Hsin-Hsi Tsai,Bo-Ching Lee,Ya-Fang Chen,Jiann-Shing Jeng,Li-Kai Tsai 대한뇌졸중학회 2022 Journal of stroke Vol.24 No.3

Background and Purpose Cerebral venous flow alterations potentially contribute to age-related white matter changes, but their role in small vessel disease has not been investigated. Methods This study included 297 patients with hypertensive intracerebral hemorrhages (ICH) who underwent magnetic resonance imaging. Cerebral venous reflux (CVR) was defined as the presence of abnormal signal intensity in the dural venous sinuses or internal jugular vein on time-of-flight angiography. We investigated the association between CVR, dilated perivascular spaces (PVS), and recurrent stroke risk. Results CVR was observed in 38 (12.8%) patients. Compared to patients without CVR those with CVR were more likely to have high grade (>20 in the number) dilated PVS in the basal ganglia (60.5% vs. 35.1%; adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.25 to 5.60; P=0.011) and large PVS (>3 mm in diameter) (50.0% vs. 18.5%; aOR, 3.87; 95% CI, 1.85 to 8.09; P<0.001). During a median follow-up of 18 months, patients with CVR had a higher recurrent stroke rate (13.6%/year vs. 6.2%/year; aOR, 2.53; 95% CI, 1.09 to 5.84; P=0.03) than those without CVR. Conclusions CVR may contribute to the formation of enlarged PVS and increase the risk of recurrent stroke in patients with hypertensive ICH.

Multimorbidity Pattern and Risk for Mortality Among Patients With Dementia: A Nationwide Cohort Study Using Latent Class Analysis

Che-Sheng Chu,Shu-Li Cheng,Ya-Mei Bai,Tung-Ping Su,Shih-Jen Tsai,Tzeng-Ji Chen,Fu-Chi Yang,Mu-Hong Chen,Chih-Sung Liang 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.9

Objective Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk.Methods This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate.Results With adjustment for age, a three-class model was identified, with 42.7% of participants classified as “low comorbidity class (cluster 1)”, 44.2% as “cardiometabolic multimorbidity class (cluster 2)”, and 13.1% as “FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract).” The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708–14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281–1.953; p<0.001) in cluster 3.Conclusion Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.