INTRODUCTIONColorectal cancer is the most common form of malignancy in Taiwan and the third leading cause of death from cancer, preceded only by lung and hepatic cancers. Colorectal cancer is typically treated by surgical intervention and/or chemotherapy and radiotherapy, if necessary. To date, 5-fluorouracil (5-FU) is the most commonly used anti-cancer chemotherapy drug. However, patients commonly experience resistance to the drug therefore limiting its efficiency. In this study, we measured the expression of rTSbeta in human colon cancer as a novel 5-FU resistance marker.

MATERIALS AND METHODSWe collected 172 colon cancer samples from 4 different hospitals (including 21 pairs of colon cancer biopsies and 151 pathologic slides of colon cancer). In vitro, we measured the cytotoxicity of 5-FU and 5-FU plus leucovorin in H630 and H630-1 colon cancer cell lines.

RESULTSThe results revealed that rTSbeta was expressed in 115 (66.9 %) pathology samples and that tumour expression was higher than in corresponding normal tissue. Survival rates of up to 5 years following treatment was significantly higher for patients without rTSbeta expression than for those with rTSbeta expression (P = 0.0023). In vitro, H630-1 (with rTSbeta overexpression) had significantly higher IC50 of 5-FU than did H630. IC50 of 5-FU decreased when leucovorin was added.

CONCLUSIONSResults indicate a close relationship between rTSbeta expression and resistance to the drug 5-FU in human colorectal cancer. These results provide further evidence for rTSbeta expression as a novel 5-FU resistance marker of colorectal cancer.

Biomarkers ; Cell Line, Tumor ; drug effects ; Colorectal Neoplasms ; drug therapy ; Cytological Techniques ; Drug Resistance, Neoplasm ; physiology ; Fluorouracil ; pharmacology ; therapeutic use ; Humans ; In Vitro Techniques ; Taiwan ; Thymidylate Synthase ; genetics ; metabolism

Traditional acute kidney injury (AKI) classifications, which are centered around semi-anatomical lines, can no longer capture the complexity of AKI. By employing strategies to identify predictive and prognostic enrichment targets, experts could gain a deeper comprehension of AKI’s pathophysiology, allowing for the development of treatment-specific targets and enhancing individualized care. Subphenotyping, which is enriched with AKI biomarkers, holds insights into distinct risk profiles and tailored treatment strategies that redefine AKI and contribute to improved clinical management. The utilization of biomarkers such as N-acetyl-β-D-glucosaminidase, tissue inhibitor of metalloprotease-2·insulin-like growth factor-binding protein 7, kidney injury molecule-1, and liver fatty acid-binding protein garnered significant attention as a means to predict subclinical AKI. Novel biomarkers offer promise in predicting persistent AKI, with urinary motif chemokine ligand 14 displaying significant sensitivity and specificity. Furthermore, they serve as predictive markers for weaning patients from acute dialysis and offer valuable insights into distinct AKI subgroups. The proposed management of AKI, which is encapsulated in a structured flowchart, bridges the gap between research and clinical practice. It streamlines the utilization of biomarkers and subphenotyping, promising a future in which AKI is swiftly identified and managed with unprecedented precision. Incorporating kidney biomarkers into strategies for early AKI detection and the initiation of AKI care bundles has proven to be more effective than using care bundles without these novel biomarkers. This comprehensive approach represents a significant stride toward precision medicine, enabling the identification of high-risk subphenotypes in patients with AKI.

Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g -1 •hour -1 for 7 days) was intraperitoneally infused into male Sprague–Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100β-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2 + -Beclin 1 + and SOX2 + -S100β + cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.

INTRODUCTIONProblem-based learning (PBL), a pedagogic concept using a student-centred approach and problem-solving through small group discussions, has been adopted in varying degrees for years at all 11 medical institutes in Taiwan. Much evidence has shown that a number of factors can seriously affect student performance in PBL courses, such as the design of PBL scenarios, the tutors' character and students' attitudes and efforts.

MATERIALS AND METHODSThe aim of this study was to examine how the personal characters or knowledge base of Taiwanese medical students influence their performance in a hybrid-PBL curriculum. A total of 309 (234 male, 75 female) high-school entry undergraduate medical students participated in this survey. Self-assessed personal traits were presented in a 44-item questionnaire with a Big Five factor structure. Knowledge base was assessed by students' score point average (SPA) based on their previous 4-year education in medical school. Peer-assessed performance of students in the PBL curriculum was carried out using a well-developed, reliable and validated evaluation form.

RESULTSEach student's peer-evaluated PBL performance can be divided into 5 principal components, which included control-lead, assist-coordinate, written organisation and compromise- comply (Eigen value >1). The consistency and reliability of the Big Five questionnaire on personal traits was analysed and discordant items were deleted (Cronbach's alpha = 0.72 to 0.86 after deletion). The relationship between the personal traits, knowledge base and PBL performance, as analysed by simple regression, showed that "extraversion" and "openness to experience" were positively related to the "assist-coordinate" characteristic in PBL performance, and "conscientiousness" was positively related to the "control-lead" characteristic in PBL performance. The SPA was positively related to the "assist-coordinate" or "control-lead" characteristic in PBL performance. The "agreeableness" was negatively correlated with the "control-lead" characteristic in PBL performance. After stepwise regression between the Big Five and each component of PBL performance, only the correlation between conscientiousness and control/lead, and between extraversion and assist/coordinate remained significant.

CONCLUSIONKnowledge and personality characteristics appear to be associated with student performance in a hybrid-PBL curriculum. The implications of this study on the future development and application of this assessment tool in medical schools are presented.

Educational Measurement ; Female ; Humans ; Male ; Mental Competency ; psychology ; Problem-Based Learning ; methods ; Retrospective Studies ; Students, Medical ; psychology ; Surveys and Questionnaires ; Taiwan

Post-traumatic hydrocephalus (PTH) is a commonly encountered complication following decompressive craniectomy, and is usually characterized by symptoms including headache, nausea, vomiting, and papilledema. Extracranial herniation accompanied by hemiplegia is a rare complication in patients with PTH who underwent craniectomy after subdural hematoma removal. We report a case of PTH that presented with extracranial herniation within one month of decompressive craniectomy. Following ventriculoperitoneal shunt implantation, left hemiplegia improved dramatically with restoration of the left middle cerebral artery blood flow, which was evident on serial imaging. Vascular compromise is often overshadowed by increased intracranial pressure when clinicians are dealing with traumatic brain injury patients. Delicate neurological and radiological examinations and prompt early interventions could lead to optimal outcomes in patients receiving decompressive craniectomy.

Background: and Purpose Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history. Methods: We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura. Results: We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group. Conclusions This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.