Taipei Hospital

Cancer stem cells (CSCs) play pivotal roles in tumor relapse, metastasis, and therapy resistance. Interleukin 17 receptor A (IL-17RA) is a key mediator in colorectal cancer (CRC) pathogenesis and progression. Our recent study demonstrated that reduced IL-17RA expression correlates with favorable prognosis in CRC patients and suppresses tumor growth in murine models. This study aimed to investigate the role of IL-17RA in promoting cancer stem-like properties and its impact on colorectal cancer prognosis and chemoresistance. Expression levels of IL-17RA and CSC markers in CRC cells were evaluated using quantitative real-time polymerase chain reaction and Western blotting. Kaplan-Meier analysis of 68 CRC patients revealed that high IL-17RA expression is associated with poor clinical outcomes. To investigate IL-17RA's functional role, CRC cells with stable IL-17RA overexpression were analyzed for changes in CSC marker expression, sphere formation, and 5-fluorouracil (5-FU) resistance. IL-17RA overexpression significantly increased CSC marker expression, including cluster of differentiation 133 (CD133), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), sex determining region Y-box 2 (SOX2), and enhanced tumor sphere formation and 5-FU resistance in SW620 cells. Specific inhibitors of IL-17RA signaling, such as the STAT3 inhibitor Stattic, reduced the expression of CD133, LGR5, ALDHA1, SOX2 and c-MYC, as well as tumor sphere formation in SW620 cells. These findings elucidate a novel IL-17RA-STAT3 axis that regulates CSC properties in CRC and highlight IL-17RA as a promising prognostic biomarker and therapeutic target for CRC treatment.

Background: Hypertension is a leading risk factor for cardiovascular disease and is highly prevalent in Asian populations. However, most genome-wide association studies (GWASs) and transcriptome-wide association studies (TWASs) have primarily focused on individuals of European ancestry, limiting generalizability to other ethnic groups. Hypothesis: We hypothesized that integrating GWAS, TWAS, and expression quantitative trait locus (eQTL) analyses in a large Taiwanese cohort would uncover novel hypertension-associated genetic loci and gene expression profiles relevant to Asian populations. Methods: We performed the first combined GWAS, TWAS, and eQTL analysis of hypertension using data from the Taiwan Biobank, including 10,739 hypertensive patients and 49,668 normotensive controls, with 4,512,191 genome-wide single nucleotide polymorphisms (SNPs). GWAS identified susceptibility loci, TWAS assessed gene-level associations, and eQTL analysis linked significant variants to gene expression changes in whole blood. Results: We identified 14 genetic loci significantly associated with hypertension, including one novel locus at 5p13.1. eQTL analysis revealed that this locus was significantly associated with DAB2 expression in whole blood. TWAS identified 55 hypertension-associated genes, 20 (36%) of which overlapped with GWAS loci. Notably, several genes outside of GWAS-identified loci—such as FBXL15 , KCNIP2 , and CRIP3 —were highly significant in TWAS and are implicated in vascular function and blood pressure regulation. Conclusions: This integrative genomic and transcriptomic study highlights novel genetic contributors to hypertension in an East Asian population. The findings improve our understanding of hypertension biology and may inform future precision medicine approaches for risk prediction and therapeutic development in diverse populations.

We determined the complete mitochondrial genome sequence of the White-lipped Tree Frog, Polypedates leucomystax, in Okinawa, Japan, from a single individual. The mitochondrial genome encoded 13 protein-coding genes, two rRNAs, 22 tRNAs, and two control regions (D-loops). When compared using full-length mitochondrial genome sequences, our mitochondrial genome is most similar to that of P. leucomystax from Thailand (94.5%). From the phylogenetic analysis of partial mitochondrial genome sequences, P. leucomystax was divided into three subgroups: western (Myanmar), central (Malaysia and Thailand), and central/eastern (Indonesia, Philippines, and Japan). The mitochondrial genome sequences from the Okinawa and Thailand frogs were representative sequences of central/eastern and central subgroups, respectively. In spite of the high similarity between the Okinawa and Thailand frogs' mitochondrial genome sequences, we found a difference in length and the sequence in the second D-loop. In this region, we found a repetitive sequence region, which was composed of an 86-bp sequence with 13- and 14-bp spacer sequences. The repetitive sequence regions were different in length, copy number, the combination of the 86-bp, and the spacer sequences among eight individuals of P. leucomystax in Okinawa, Japan.

Formosan serows are an endemic species in Taiwan. Alfaxalone, a γ-aminobutyric acidA agonist, induces or maintains anesthesia in various veterinary species with reported potential adverse effects of respiratory depression and tachycardia. α2-Adrenoceptor agonists exert sedative and muscle relaxation effects, along with substantial cardiovascular adverse effects. Here, we aimed to evaluate the anesthetic effects of alfaxalone combined with xylazine or dexmedetomidine (AX vs. AD, respectively) in Formosan serows. In this randomized, masked study, AX was administered to four serows, and AD was administered to five serows intramuscularly via blow dart. The time and score of induction and recovery were recorded. Post-intubation, isoflurane was administered for maintenance anesthesia. Heart rate (HR), respiratory rate (RR), peripheral saturation of oxygenation (SpO2), rectal temperature (RT), and end-tidal CO2 (EtCO2) were recorded every five to eight minutes. Atipamezole and tolazoline were administered to antagonize dexmedetomidine and xylazine post-procedure, respectively. Both combinations allowed smooth induction and recovery. The AD group exhibited significantly lower HR and SpO2 and significantly higher RT and EtCO2 than the AX group (both p < 0.01). The AD-treated serows exhibited notable muscle rigidity after induction and significant hypoventilation and hypoxemia during the procedure. Although alfaxalone combined with dexmedetomidine or xylazine can produce satisfactory induction and recovery in Formosa serows, notable hypoxemia and hypoventilation are induced by the alfaxalone-dexmedetomidine combination compared to the alfaxalone-xylazine combination.

Molecular data from 35 of the 50 Acrossocheilinae species suggest that the species‐level diversity in the subfamily has been overestimated, likely due to inadequate taxon and geographic sampling and reliance on morphological characters that vary intraspecifically. Three new genera, one resurrected genus, two resurrected species, and one new species are diagnosed and described herein. Nine synonyms of three valid species of Acrossocheilinae are recognized from the Yangtze, Xijiang, Song Hong, Annamite, and Mekong ecoregions in East and Southeast Asia. Thirty‐two valid and six putative new species are indicated by molecular data and a key to the genera is provided. As more molecular and morphological data become available, additional taxonomic changes in this widespread and generally poorly known subfamily are likely.

Many patients with leukoaraiosis (LA) exhibit mild and difficult-to-detect symptoms in the early stages, and due to the lack of effective detection methods, the optimal timing for treatment is often missed. This not only makes later treatment more difficult but, in severe cases, can even lead to mild to severe dementia. Therefore, in addition to relying on radiologists to manually interpret magnetic resonance imaging (MRI) scans, finding more effective detection methods has become extremely urgent. This study aimed to combine image processing and deep learning technologies to develop a model capable of accurately identifying and segmenting white matter hyperintensities (WMHs) to assist doctors in the early diagnosis of LA. We first performed efficient preprocessing on MR image slices from two different series and used the ResNet18 model to identify key slices containing WMHs, ultimately achieving precise segmentation of WMH areas with the U-Net model. This research focused on developing innovative preprocessing techniques, improving the accuracy by 12.3% with a limited dataset through preprocessing. Ultimately, the ResNet18 model achieved an F1 score of 0.829, while the U-Net model's intersection over union (IoU) and Dice coefficient reached 0.750 and 0.857, respectively, showing the potential of this architecture. We propose improvements in the final chapter to construct a more comprehensive model.

In recent years, many fields have expanded their research methods through the integration of artificial intelligence. In the current medical field, it is widely used in image recognition to diagnose patient symptoms, train clinical prediction models, and improve clinical workflow processes to avoid missing treatment opportunities. These methods have all achieved good results so far. Now, generative AI is also impacting the development of the medical field, not only generating prescriptions that match patient conditions but also being applied in generating medical images for data augmentation and simulating various pathological conditions, thereby aiding in training deep learning models. Stroke is a leading cause of death or disability, ranking as the second leading cause of death worldwide, next to cancer. If cancers were categorized individually, stroke would surpass all single diseases, making it a primary focus of research in brain disease treatment. There are already studies where generative AI has been used to create medical images, which are then manually evaluated by doctors to determine if they were generated by AI. In this project, we plan to generate CT images of strokes using generative AI and use a trained model (to diagnose stroke) to improve accuracy. Through this project, we hope to solve the problem of scarce stroke CT images while also providing support for training stroke-related models.