Senescence induces miR-409 to down-regulate CCL5 and impairs angiogenesis in endothelial progenitor cells.

This study explores the impact of senescence on autocrine C-C motif chemokine ligand 5 (CCL5) in human endothelial progenitor cell (EPCs), addressing the poorly understood decline in number and function of EPCs during ageing. We examined the effects of replication-induced senescence on CCL5/CCL5 receptor (CCR5) signalling and angiogenic activity of EPCs in vitro and in vivo. We also explored microRNAs controlling CCL5 secretion in senescent EPCs, its impact on EPC angiogenic activity, and validated our findings in humans. CCL5 secretion and CCR5 levels in senescent EPCs were reduced, leading to attenuated angiogenic activity. CCL5 enhanced EPC proliferation via the CCR5/AKT/P70S6K axis and increased vascular endothelial growth factor (VEGF) secretion. Up-regulation of miR-409 in senescent EPCs resulted in decreased CCL5 secretion, inhibiting the angiogenic activity, though these negative effects were counteracted by the addition of CCL5 and VEGF. In a mouse hind limb ischemia model, CCL5 improved the angiogenic activity of senescent EPCs. Analysis involving 62 healthy donors revealed a negative association between CCL5 levels, age and Framingham Risk Score. These findings propose CCL5 as a potential biomarker for detection of EPC senescence and cardiovascular risk assessment, suggesting its therapeutic potential for age-related cardiovascular disorders.

Hsa-miR-134-5p predicts cardiovascular risk in circulating mononuclear cells and improves angiogenic action of senescent endothelial progenitor cells.

This research explores the role of microRNA in senescence of human endothelial progenitor cells (EPCs) induced by replication. Hsa-miR-134-5p was found up-regulated in senescent EPCs where overexpression improved angiogenic activity. Hsa-miR-134-5p, which targeted transforming growth factor ß-activated kinase 1-binding protein 1 (TAB1) gene, down-regulated TAB1 protein, and inhibited phosphorylation of p38 mitogen-activated protein kinase (p38) in hsa-miR-134-5p-overexpressed senescent EPCs. Treatment with siRNA specific to TAB1 (TAB1si) down-regulated TAB1 protein and subsequently inhibited p38 activation in senescent EPCs. Treatment with TAB1si and p38 inhibitor, respectively, showed angiogenic improvement. In parallel, transforming growth factor Beta 1 (TGF-ß1) was down-regulated in hsa-miR-134-5p-overexpressed senescent EPCs and addition of TGF-ß1 suppressed the angiogenic improvement. Analysis of peripheral blood mononuclear cells (PBMCs) disclosed expression levels of hsa-miR-134-5p altered in adult life, reaching a peak before 65 years, and then falling in advanced age. Calculation of the Framingham risk score showed the score inversely correlates with the hsa-miR-134-5p expression level. In summary, hsa-miR-134-5p is involved in the regulation of senescence-related change of angiogenic activity via TAB1-p38 signalling and via TGF-ß1 reduction. Hsa-miR-134-5p has a potential cellular rejuvenation effect in human senescent EPCs. Detection of human PBMC-derived hsa-miR-134-5p predicts cardiovascular risk.

Demographics and medical burden of osteogenesis imperfecta: a nationwide database analysis.

The epidemiological data on osteogenesis imperfecta (OI) in Asia is limited. This study, representing the first comprehensive epidemiological investigation on OI in Taiwan, reveals high medical resource utilization and underscores the importance of early diagnosis to enhance care quality. INTRODUCTION: This study examines osteogenesis imperfecta, a hereditary connective tissue disorder causing pediatric fractures and limb deformities, using a nationwide database from Taiwan to analyze clinical features and medical burden. METHODS: The study identified validated OI patients from the Catastrophic Illness Registry in the National Health Insurance Research Database from 2008 to 2019. Demographic data and medical resource utilization were analyzed. A multivariate Cox model assessed the influence of sex, validation age, and comorbidities. RESULTS: 319 OI patients (M/F = 153/166) were identified, with 58% validated before age 20. Prevalence and incidence were 0.8-1.3/100,000 and 0.02-0.09/100,000, respectively, with higher rates in the pediatric demographic. In the study period, 69.6% of the patients had admission history, primarily to pediatric and orthopedic wards. The median admission number was 3, with a median length of stay of 12 days and a median inpatient cost of approximately 3,163 USD during the period. Lower limb fractures were the main reason for hospitalization. 57% of OI patients received bisphosphonate treatment. The leading causes of mortality were OI-related deaths, neurovascular disease, and cardiovascular disease. The median age of validation in the non-survival group was significantly higher compared to the survival group (33 vs. 14 years), and patients validated during childhood required more inpatient fracture surgeries than those validated during adulthood. CONCLUSION: This study provides comprehensive real-world evidence on the clinical characteristics and high medical resource utilization of OI patients in a low prevalence region like Taiwan. Early diagnosis is crucial for improving care quality and enhancing health outcomes.

Quantitative DNA Methylation Analysis and Epigenotype-Phenotype Correlations in Taiwanese Patients with Silver-Russell Syndrome.

Background: Silver-Russell syndrome (SRS; OMIM #180860) is a clinically and genetically heterogeneous imprinting disorder characterized by prenatal and postnatal growth failure. The aim of this study was to identify the epigenotype-phenotype correlations in these patients using quantitative DNA methylation analysis. Methods: One hundred and eighty-three subjects clinically suspected of having SRS were referred for diagnostic testing by the methylation profiling of H19-associated imprinting center (IC) 1 and imprinted PEG1/MEST regions using methylation-specific high-resolution melting analysis and methylation quantification with the MassARRAY assay. Correlations between quantitative DNA methylation status and clinical manifestations of the subjects according to the Netchine-Harbison (N-H) clinical scoring system for SRS were analyzed. Results: Among the 183 subjects, 90 had a clinical diagnosis of SRS [N-H score ≥ 4 (maximum = 6)] and 93 had an SRS score < 4. Molecular lesions were detected in 41% (37/90) of the subjects with a clinical diagnosis of SRS, compared with 3% (3/93) of those with an N-H score < 4. The IC1 methylation level was negatively correlated with the N-H score. The molecular diagnosis rate was positively correlated with the N-H score. Thirty-one subjects had IC1 hypomethylation (IC1 methylation level <35% by the MassARRAY assay), seven had maternal uniparental disomy 7, and two had pathogenic copy number variants. Among the 90 subjects with an N-H score ≥ 4, the IC1 methylation level was significantly different between those with or without some clinical SRS features, including birth length ≤ 10th centile, relative macrocephaly at birth, normal cognitive development, body asymmetry, clinodactyly of the fifth finger, and genital abnormalities. Conclusions: This study confirmed the suitability of the N-H clinical scoring system as clinical diagnostic criteria for SRS. Quantitative DNA methylation analysis using the MassARRAY assay can improve the detection of epigenotype-phenotype correlations, further promoting better genetic counseling and multidisciplinary management for these patients.

Hsa-miR-409-3p regulates endothelial progenitor senescence via PP2A-P38 and is a potential ageing marker in humans.

We explored the roles of hsa-microRNA (miR)-409-3p in senescence and signalling mechanism of human endothelial progenitor cells (EPCs). Hsa-miR-409-3p was found upregulated in senescent EPCs. Overexpression of miRNA mimics in young EPCs inhibited angiogenesis. In senescent EPCs, compared to young EPCs, protein phosphatase 2A (PP2A) was downregulated, with activation of p38/JNK by phosphorylation. Young EPCs treated with siPP2A caused inhibited angiogenesis with activation of p38/JNK, similar to findings in senescent EPCs. Time series analysis showed, in young EPCs treated with hsa-miR-409-3p mimics, PP2A was steadily downregulated for 72 h, while p38/JNK was activated with a peak at 48 hours. The inhibited angiogenesis of young EPCs after miRNA-409-3p mimics treatment was reversed by the p38 inhibitor. The effect of hsa-miR-409-3p on PP2A signalling was attenuated by exogenous VEGF. Analysis of human peripheral blood mononuclear cells (PBMCs) obtained from healthy people revealed hsa-miR-409-3p expression was higher in those older than 65 years, compared to those younger than 30 years, regardless of gender. In summary, hsa-miR-409-3p was upregulated in senescent EPCs and acted as a negative modulator of angiogenesis via targeting protein phosphatase 2 catalytic subunit alpha (PPP2CA) gene and regulating PP2A/p38 signalling. Data from human PBMCs suggested hsa-miR-409-3p a potential biomarker for human ageing.

Combining Panel-Based Next-Generation Sequencing and Exome Sequencing for Genetic Liver Diseases.

OBJECTIVES: To determine how advanced genetic analysis methods may help in clinical diagnosis. STUDY DESIGN: We report a combined genetic diagnosis approach for patients with clinical suspicion of genetic liver diseases in a tertiary referral center, using tools either tier 1: Sanger sequencing on SLC2SA13, ATP8B1, ABCB11, ABCB4, and JAG1 genes, tier 2: panel-based next generation sequencing (NGS), or tier 3: whole-exome sequencing (WES) analysis. RESULTS: In a total of 374 patients undergoing genetic analysis, 175 patients received tier 1 Sanger sequencing based on phenotypic suspicion, and pathogenic variants were identified in 38 patients (21.7%). Tier 2 included 216 patients (39 of tier 1-negative patients) who received panel-based NGS, and pathogenic variants were identified in 60 (27.8%). In tier 3, 41 patients received WES analysis, and 20 (48.8%) obtained genetic diagnosis. Pathogenic variants were detected in 6 of 19 (31.6%) who tested negative in tier 2, and a greater detection rate in 14 of 22 (63.6%) patients with deteriorating/multiorgan disease receiving one-step WES (P = .041). The overall disease spectrum is comprised of 35 genetic defects; 90% of genes belong to the functional categories of small molecule metabolism, ciliopathy, bile duct development, and membrane transport. Only 13 (37%) genetic diseases were detected in more than 2 families. A hypothetical approach using a small panel-based NGS can serve as the first tier with diagnostic yield of 27.8% (98/352). CONCLUSIONS: NGS based genetic test using a combined panel-WES approach is efficient for the diagnosis of the highly diverse genetic liver diseases.

Platelet-derived biomaterial with hyaluronic acid alleviates temporal-mandibular joint osteoarthritis: clinical trial from dish to human.

BACKGROUND: Bioactive materials have now raised considerable attention for the treatment of osteoarthritis (OA), such as knee OA, rheumatoid OA, and temporomandibular joint (TMJ) OA. TMJ-OA is a common disease associated with an imbalance of cartilage regeneration, tissue inflammation, and disability in mouth movement. Recently, biological materials or molecules have been developed for TMJ-OA therapy; however, ideal treatment is still lacking. In this study, we used the combination of a human platelet rich plasma with hyaluronic acid (hPRP/HA) for TMJ-OA therapy to perform a clinical trial in dish to humans. METHOD: Herein, hPRP was prepared, and the hPRP/HA combined concentration was optimized by MTT assay. For the clinical trial in dish, pro-inflammatory-induced in-vitro and in-vivo mimic 3D TMJ-OA models were created, and proliferation, gene expression, alcian blue staining, and IHC were used to evaluate chondrocyte regeneration. For the animal studies, complete Freund's adjuvant (CFA) was used to induce the TMJ-OA rat model, and condyle and disc regeneration were investigated through MRI. For the clinical trial in humans, 12 patients with TMJ-OA who had disc displacement and pain were enrolled. The disc displacement and pain at baseline and six months were measured by MRI, and clinical assessment, respectively. RESULTS: Combined hPRP/HA treatment ameliorated the proinflammatory-induced TMJ-OA model and promoted chondrocyte proliferation by activating SOX9, collagen type I/II, and aggrecan. TMJ-OA pathology-related inflammatory factors were efficiently downregulated with hPRP/HA treatment. Moreover, condylar cartilage was regenerated by hPRP/HA treatment in a proinflammatory-induced 3D neocartilage TMJ-OA-like model. During the animal studies, hPRP/HA treatment strongly repaired the condyle and disc in a CFA-induced TMJ-OA rat model. Furthermore, we performed a clinical trial in humans, and the MRI data demonstrated that after 6 months of treatment, hPRP/HA regenerated the condylar cartilage, reduced disc displacement, alleviated pain, and increased the maximum mouth opening (MMO). Overall, clinical trials in dish to human results revealed that hPRP/HA promoted cartilage regeneration, inhibited inflammation, reduced pain, and increased joint function in TMJ-OA. CONCLUSION: Conclusively, this study highlighted the therapeutic potential of the hPRP and HA combination for TMJ-OA therapy, with detailed evidence from bench to bedside. Trial registration Taipei Medical University Hospital (TMU-JIRB No. N201711041). Registered 24 November 2017. https://tmujcrc.tmu.edu.tw/inquiry_general.php .

Childhood neurodevelopmental disorders and maternal diabetes: A population-based cohort study.

AIM: To assess the risk of a wide spectrum of neurodevelopmental disorders (NDDs) in offspring of mothers with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). METHOD: This retrospective cohort study included 877 233 singletons born between 2004 and 2008 in Taiwan. Children were followed up to 2015 for diagnoses of NDDs, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), developmental delay, intellectual disability, cerebral palsy, and epilepsy/infantile spasms using health insurance claims data. We performed Cox regression models to estimate the relative risks of NDDs associated with maternal diabetes. Covariates included parental age, year of birth, child sex, family income, urbanization level, hypertensive disorder, and preterm delivery status. RESULTS: In utero there were 338 (0.04%) children exposed to T1DM, 8749 (1.00%) to T2DM, and 90 200 (10.28%) to GDM. The effect of T1DM on NDDs was the largest, followed by T2DM, then GDM. T1DM was associated with an increased risk of developmental delay, intellectual disability, and epilepsy/intellectual spasms in offspring. T2DM was associated with an increased risk of ASD, ADHD, developmental delay, intellectual disability, cerebral palsy, and epilepsy/intellectual spasms. GDM was associated with an increased risk of ASD, ADHD, and developmental delay. INTERPRETATION: Maternal diabetes during pregnancy, including T1DM, T2DM, and GDM, is associated with an increased risk of some NDDs in offspring.

Developing the Chinese version problem areas in diabetes-teen for measuring diabetes distress in adolescents with type 1 diabetes.

PURPOSE: To translate the 26-item English version Problem Areas in Diabetes-Teen (PAID-T) into a Chinese version and then to examine its psychometrical properties for measuring diabetes distress in adolescents with type 1 diabetes (T1D). DESIGN AND METHODS: The 26-item English version PAID-T was translated into a Chinese version guided by the translation model for cross-cultural research. A cross-sectional design was used and 203 adolescents with T1D were recruited from four hospitals in Taiwan. Content validity, exploratory factor analysis, and item analysis were used to ensure the item quality and build the factor structure of the Chinese version PAID-T. Confirmatory factor analysis, concurrent validity, and reliability testing were also used to examine its psychometric properties. RESULTS: The three second-order factors of the 18-item Chinese version PAID-T were developed. The correlation coefficients of the three-factor Chinese version PAID-T with self-management and glycosylated hemoglobin levels were all significant and ranged from -0.32 to -0.45 and 0.18 to 0.33 respectively. Cronbach's α and the test-retest reliability of the three-factor Chinese version PAID-T ranged from 0.85 to 0.93 and from 0.89 to 0.94 respectively. CONCLUSIONS: The Chinese version PAID-T with good translation quality was a reliable and valid scale to screen and assess diabetes distress for adolescents with T1D. PRACTICE IMPLICATIONS: Nurses could use the Chinese version PAID-T to track diabetes distress and tailor interventions for adolescents with T1D; also, the Chinese version PAID-T could facilitate the conducting of research on diabetes distress for adolescents with T1D.

Is Non-Stimulated C-Peptide at Diagnosis a Good Predictive Value for Insulin Use at Two Years after Diagnosis in Pediatric Diabetic Patients?

Background and Objectives: Insulin treatment may be initially required to stabilize patients presenting with metabolic crisis at type 1 and 2 diabetes mellitus (DM) onset. Some patients with type 2 DM may need persistent insulin treatment. This study aimed to examine the predictive performance of non-stimulated C-peptide level at the time of diagnosis for future insulin use in pediatric diabetic patients. Materials and Methods: We reviewed the medical charts of diabetic patients aged 18 years or younger in a medical center in southern Taiwan from January 2000 to December 2019. Clinical and individual data were collected at the time of DM diagnosis. Outcomes were persistent insulin use at the time of diagnosis, as well as at one and two years after diagnosis. Results: The final analysis included a total of 250 patients. The best cut-off point of non-stimulated C-peptide was 0.95 ng/mL, and the predictive indices for the insulin use were 0.84 for sensitivity and 0.94 for specificity at two years after DM diagnosis. Incorporating age at onset and presence of GAD antibodies can further increase the predictive power of non-stimulated C-peptide. Conclusions: The value of non-stimulated C-peptide at diabetic onset was feasible and effective for predicting future insulin treatment up to the time point of two years after diagnosis.

De novo mutation and skewed X-inactivation in girl with BCAP31-related syndrome.

Full genome analysis of a young girl with deafness, dystonia, central hypomyelination, refractory seizure, and fluctuating liver function impairment revealed a heterozygous, de novo variant in the BCAP31 gene on chromosome Xq28 (NM_001256447.2:c.92G>A), mutations of which caused the X-linked recessive severe neurologic disorder deafness, dystonia, and cerebral hypomyelination. Reverse transcription-polymerase chain reaction of the patient's white blood cells showed the absence of wild-type BCAP31 messenger RNA (mRNA) but the presence of two novel BCAP31 mRNAs. The major alternatively spliced mRNA is due to Exon 2 skipping and the utilization of a new initiation site in Exon 3 that leads to a frameshift and truncated transcript while the minor novel mRNA has a 110 nucleotide insertion to Exon 2. Phasing studies showed that the de novo variant arose in the paternal X chromosome. X chromosome inactivation assay was done and confirmed that the patient's maternal X chromosome was preferentially inactivated, providing evidence that the mutated BCAP31 gene was the one predominantly expressed. According to the American College of Medical Genetics and Genomics guideline, this variant is deemed "pathogenic" (PS2, PS3, PM2, PP3, and PP4) and deleterious. This is the first reported female patient in BCAP31-related syndrome resulted from skewed X-inactivation and a de novo mutation in the active X chromosome.

Impact of periodontal disease and chewing ability on the quality of life of the elderly in an affluent community.

BACKGROUND/PURPOSE: Improvement of the medical and social environment is an important aspect of government policies in assuring the quality of life (QoL) of older adults. However, few studies have appraised the impact and relationship of QoL with clinical factors among elderly individuals in affluent residential areas. METHODS: A total of 166 older adults from Chang Gung Health and Culture Village were enrolled. Oral health-related QoL was measured using the Geriatric Oral Health Assessment Index. Self-assessed chewing abilities and demographic characteristics were collected by questionnaire. Physical health was scored by activities of daily living (ADL) and instrumental ADL. Mini nutrition assessment questionnaire was used to evaluate the nutritional intake. Multiple linear regression was used to predict risk factors affecting QoL and to examine whether chewing ability was a mediator of oral health-related QoL. RESULTS: Poor chewing ability was associated with older age (OR = 1.82 for 76-85 years and 3.58 for 86-95 years), sufficient economic status (OR = 5.55) and removable denture-wearing (OR = 7.52). On the other hand, poor chewing ability (OR = 0.11), removable denture-wearing (OR = 0.48), periodontal disease (OR = 0.38) had lower likelihood of good oral health-related QoL. Mediator analyses showed that chewing ability was a mediator for the association between oral health-related QoL and economic status or removable denture-wearing or having more than 20 teeth. Periodontal disease was an independent factor for oral health-related QoL. CONCLUSION: Among older adults in an affluent community, periodontal disease is an independent risk factor directly related to oral health-related QoL, whereas chewing ability is a mediator between QoL and removable denture-wearing.

Luminescence material characterizations on laser-phosphor lighting techniques.

This study examines three different types of laser carriers, including the phosphors in silicone (PiS), the phosphor in glass (PiG), and alumina-based ceramic binders (CP), for laser-phosphor lighting characterizations via a laser projector light source module. The thermal influence of heat spreading on these phosphor materials and their luminescence performance is also investigated. The conversion efficiency of PiS, PiG and CP was found to be 29.7%, 34.6% and 31.8%, with their corresponding maximum laser power operations of 3.9 W, 7.9 W, and 17.2 W, respectively. This work further correlates the maximum laser operation power with the thermal conductivity of luminescence material. From the optical engine perspective, it was found that CP exhibits the superior thermal conductivity of 17.0 W/m⋅K for slight hot-spot IR observation and higher laser power operation. This work finally delivers a CP device for 50.2W maximum laser operation with the operating temperature below 100 °C. The simulation is also carried out in order to examine spreading resistance's influence, when subject to convective boundary condition. CP's response sensitivity to heat transfer coefficient was found to be rather small.

Critical Trio Exome Benefits In-Time Decision-Making for Pediatric Patients With Severe Illnesses.

OBJECTIVES: Critical illnesses caused by undiagnosed genetic conditions are challenging in PICUs. Whole-exome sequencing is a powerful diagnostic tool but usually costly and often fail to arrive at a final diagnosis in a short period. We assessed the feasibility of our whole-exome sequencing as a tool to improve the efficacy of rare diseases diagnosis for pediatric patients with severe illness. DESIGN: Observational analysis. METHOD: We employed a fast but standard whole-exome sequencing platform together with text mining-assisted variant prioritization in PICU setting over a 1-year period. SETTING: A tertiary referral Children's Hospital in Taiwan. PATIENTS: Critically ill PICU patients suspected of having a genetic disease and newborns who were suspected of having a serious genetic disease after newborn screening were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Around 50,000 to 100,000 variants were obtained for each of the 40 patients in 5 days after blood sampling. Eleven patients were immediately found be affected by previously reported mutations after searching mutation databases. Another seven patients had a diagnosis among the top five in a list ranked by text mining. As a whole, 21 patients (52.5%) obtained a diagnosis in 6.2 ± 1.1 working days (range, 4.3-9 d). Most of the diagnoses were first recognized in Taiwan. Specific medications were recommended for 10 patients (10/21, 47.6%), transplantation was advised for five, and hospice care was suggested for two patients. Overall, clinical management was altered in time for 81.0% of patients who had a molecular diagnosis. CONCLUSIONS: The current whole-exome sequencing algorithm, balanced in cost and speed, uncovers genetic conditions in infants and children in PICU, which helps their managements in time and promotes better utilization of PICU resources.

Percutaneous ethanol ablation of intrahepatic arterial pseudoaneurysm: A case report.

Hepatic arterial pseudoaneurysm is a rare but potentially fatal condition that requires prompt management. We report a case of hepatic arterial pseudoaneurysm developed after radiofrequency ablation of a hepatocellular carcinoma. The patient was successfully treated with percutaneous absolute ethanol injection under ultrasound guidance. Follow-up studies with ultrasound and computed tomography for 2 years after treatment revealed no evidence of local recurrence of hepatocellular carcinoma and of the pseudoaneurysm.

Functional independence of Taiwanese children with Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder with obesity, developmental delay, short stature, and behavioral abnormalities. The study aimed to assess the functional independence in children with PWS. The Functional Independence Measure for Children (WeeFIM) was used to evaluate 81 children with PWS (44 boys and 37 girls) with a median age of 11 years 1 month (range 2 years 8 months to 20 years 2 months) were recruited between January 2013 and December 2016. The mean total WeeFIM score was 103.8 (maximum 126). Sixty-five patients (80%) had deletion type PWS, 16 (20.0%) had nondeletion type. The scores were 103.6 ± 18.5 for deletion and 104.8 ± 18.3 for nondeletion type (p = .405), 104.8 ± 19.3 in boys and 102.6 ± 17.3 in girls (p = .293). The mean self-care, mobility, and cognition scores were 47 (maximum 56), 33 (maximum 35), and 24 (maximum 35), respectively. All total scores and 18 subscores in the three functional domains were positively correlated with age (p < .05). Most children required assistance in problem-solving, comprehension, and expression. The WeeFIM identified the strengths and limitations of children with PWS and confirmed that support and supervision were needed in cognitive and self-care tasks.

Metabolic correlates of health-related quality of life among overweight and obese adolescents.

BACKGROUND: Little is known about the metabolic factors associated with the health-related quality of life (HRQOL) among obese youths. The aim of this study is to assess metabolic correlates of HRQOL in a clinical sample of Taiwanese overweight and obese (OW/OB) adolescents. METHODS: OW/OB adolescents (age 11-19 years) were recruited and compared to their normal-weight counterparts in a tertiary hospital. HRQOL was assessed by the Pediatric Quality of Life Inventory (PedsQL). Student t tests and Cohen's d were used to compare the differences in the PedsQL scores between normal-weight and OW/OB participants who were stratified by their cumulative number of cardiometabolic risk factors (CRF). Pearson's correlation and multivariate linear regression analyses were applied to identify predictors of PedsQL. RESULTS: OW/OB adolescents (n = 60) reported lower PedsQL scores than those of normal-weight peers. The negative effects were even larger in OW/OB participants with more than one CRF. Body mass index z-scores and serum alanine aminotransferase (ALT) levels were negatively correlated with overall and subscales of PedsQL (r = - 0.283 to - 0.431). Multivariate linear models showed ALT to be the most salient factor associated with poor obesity-related HRQOL. CONCLUSION: Taiwanese OW/OB adolescents, particularly those having additional CRF, reported worse HRQOL. Impaired liver functions may predispose OW/OB subjects to even worse HRQOL.

Cryptotanshinone (Dsh-003) from Salvia miltiorrhiza Bunge inhibits prostaglandin E2-induced survival and invasion effects in HA22T hepatocellular carcinoma cells.

Human hepatocellular carcinoma (HCC) is currently the second most common cancer and one of the leading causes of cancer-related mortality in Taiwan. Previous reports show that the expression of (E-type prostaglandin 2) EP2 and (E-type prostaglandin 4) EP4 are elevated in HCC and further demonstrate that Prostaglandin E2 (PGE2) induces HA22T cell proliferation and metastasis through EP2 and EP4 receptor. Danshen (root of Salvia miltiorrhiza Bunge) is a very important and popular traditional Chinese herbal medicine which is widely and successfully used against breast cancer, leukemia, pancreatic cancer, and head and neck squamous carcinoma cells. In this study, we used Cryptotansinone (Dsh-003) (MW 269.14) from Danshen to investigate their effect and corresponding mechanism of action in PGE2-treated HA22T cells. Dsh-003 inhibited HA22T cell viability and further induced cell apoptosis in PGE2-treated HA22T cells. Furthermore, Dsh-003 inhibited EP2, EP4, and their downstream effector such as p-PI3K and p-Akt expression in HA22T hepatocellular carcinoma cells. We also observed that Dsh-003 blocked PGE2-induced cell migration by down-regulating PGE2-induced ß-catenin expression and by up-regulating E-cadherin and GSK3-ß expression. All these findings suggest that Dsh-003 inhibit human HCC cell lines and could potentially be used as a novel drug for HCC treatment.

[Reflections on Occupational Health Nursing in Taiwan: Challenges and Perspectives].

The development of the occupational health nursing profession has promoted stable and healthy human resources in Taiwan. In order to improve the occupational safety, health, and healthcare of workers, the professional core competencies and role functions of occupational health nursing is of utmost importance. This article investigated the current status of occupational health nursing education, role functions, practice scope, and the development and responsibilities of professional associations and proposed the challenges to and the future prospects of the development of occupational health nursing in Taiwan. The key findings include: (1) the role functions and practice scope of occupational health nursing; (2) occupational health nursing courses should be included in the required credits of Department of Nursing and master and doctor programs in occupational health nursing should be established; (3) a certification system of occupational health nursing should be established as soon as possible; (4) the professional associations for occupational health nursing should take responsibility for continuing education and training; and (5) interdisciplinary collaborations among relevant occupational health professionals should be strengthened.