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I-Chen Chen,1 Ching-Yi Wu,2– 4 Yi-Ling Hu,2,* Yen-Ming Huang5– 7,* 1Department of Occupational Therapy, College of Nursing and Health Sciences, Da-Yeh University, Changhua, Taiwan; 2Department of Occupational Therapy and Graduate Institute of Behavioral Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; 3Healthy Aging Research Center, Chang Gung University, Taoyuan City, Taiwan; 4Department of Physical Medicine and Rehabilitation, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan; 5Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei City, Taiwan; 6School of Pharmacy, College of Medicine, National Taiwan University, Taipei City, Taiwan; 7Department of Pharmacy, National Taiwan University Hospital, Taipei City, Taiwan*These authors contributed equally to this workCorrespondence: Yen-Ming Huang, Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, No. 33, Linsen South Road, Zhongzheng District, Taipei City, 100025, Taiwan, Tel/Fax +886 2 33668784, Email yenming927@ntu.edu.tw Yi-Ling Hu, Department of Occupational Therapy and Graduate Institute of Behavioral Sciences, College of Medicine, Chang Gung University, 259, Wunhua 1st Road, Gueishan Township, Taoyuan City, Taiwan, Tel +886 3 2118800 Ext.:3057, Email huy@cgu.edu.twIntroduction: As research on cognitive training methods for older adults with mild cognitive impairment (MCI) progresses, fully immersive virtual reality cognitive training (fi-VRCT) has shown promise in enhancing cognitive function. However, its effectiveness in improving instrumental activities of daily living (IADL) and fostering independence is still unclear. This study aims to address these uncertainties by developing and validating a fi-VRCT program focused on IADL, with the goal of enhancing both cognitive function and IADL performance in older adults with MCI.Methods and Analysis: This mixed methods program evaluation study consists of three phases: feasibility, intervention, and extension. In the feasibility phase, we will implement fi-VRCT in real-world community settings and invite 20 older adults with MCI to participate in a single training session. Participants will provide feedback through questionnaires and individual interviews. The intervention phase will involve a double-blind, cluster-randomized controlled trial with 52 older adults with MCI, who will be randomly assigned to either the fi-VRCT or control groups. Both groups will complete 16 sessions over eight weeks, with cognitive and functional performance assessed at various intervals. During the extension phase, feedback will be gathered from 26 participants who underwent fi-VRCT through focus group interviews and ongoing questionnaires. Quantitative and qualitative findings will be synthesized to refine the fi-VRCT program and elucidate training outcomes. Ultimately, fi-VRCT has the potential to enhance cognitive and functional abilities in older adults with MCI in community settings.Ethics and Dissemination: Ethical approval has been obtained from the Research Ethics Committee at National Taiwan Normal University (202312EM009). The research findings will be disseminated through reputable, peer-reviewed journals and professional international conferences to engage and inform academic and clinical audiences.Trial Registration: NCT06392412.Keywords: cognitive training, instrumental activity of daily living, mild cognitive impairment, mixed-methods, older adults, virtual reality

Yen-Ming Huang,1– 3 Yao-Hsing Wang,1,4 Hsun-Yu Chan,5 Yunn-Fang Ho1,2 1Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, 100025, Taiwan; 2School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 100025, Taiwan; 3Department of Pharmacy, National Taiwan University Hospital, Taipei, 100229, Taiwan; 4Honest Pharmacy, Taichung, 408483, Taiwan; 5Department of Industrial Education, National Taiwan Normal University, Taipei, 106308, TaiwanCorrespondence: Hsun-Yu Chan, Department of Industrial Education, National Taiwan Normal University, Taipei, 106308, Taiwan, Tel +886 2 77493550, Email hsunyuchan@ntnu.edu.tw Yunn-Fang Ho, Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, 100025, Taiwan, Tel +886 2 33668794, Fax +886 2 33668780, Email yfho@ntu.edu.twPurpose: This study aimed to thoroughly document the process and cost factors involved in dispensing services within a community pharmacy.Methods: Using a cross-sectional design, this study incorporated a pragmatic and descriptive qualitative approach to outline pharmacists’ viewpoints on providing dispensing services in community settings. A purposive sampling was employed to recruit pharmacists from geographically different community pharmacies, spanning from March to July 2022. Semi-structured interviews with direct content analysis were conducted through face-to-face interactions to gather firsthand insights into pharmacists’ professional dispensing services. The data underwent analysis through descriptive and in vivo coding techniques to categorize, define, and label themes, thereby identifying key steps and cost components in the prescription dispensing process. The qualitative data management software, MAXQDA 2020, was utilized for data management and maintenance.Results: Ten community pharmacists participated in the study, cooperatively completing the interview process. Of these, 7 were male and 3 were female, with age ranging from 29 to 62 years. The average length of pharmacy practice experience was 11.4 years. The study revealed six integral steps in the dispensing process: (1) receiving and clarifying legality and completeness of prescriptions, (2) profiling and verifying patient prescriptions, (3) preparing prescription labels and containers, (4) dispensing right medications with right quantity, (5) inspecting dispensing accuracy, (6) handing over medications and providing counseling. Along with these processes, pharmacists emphasized that pharmacy manpower, representing a substantial portion of the associated costs, determines the success and quality of the dispensing service. Additionally, rental, utilities, consumables, and physical equipment were identified as other important cost factors associated with carrying out pharmacy dispensing services.Conclusion: The study offers a comprehensive understanding of the dispensing service workflow within community pharmacies. The findings may inform key stakeholders and policymakers about required resources for enhancing and sustaining quality dispensing services for the public in Taiwan.Keywords: community pharmacy, dispensing service, pharmacist, prescription, refill

Jie Chen,1,* Yen-Ming Huang,1– 3,* Hsun-Yu Chan,4 Mon-Chiao Chen,5 Yunn-Fang Ho1,2 1School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 100025, Taiwan; 2Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, 100025, Taiwan; 3Department of Pharmacy, National Taiwan University Hospital, Taipei, 100229, Taiwan; 4Department of Industrial Education, National Taiwan Normal University, Taipei, 106308, Taiwan; 5Adam’s Drug Store, Taipei, 111049, Taiwan*These authors contributed equally to this workCorrespondence: Yunn-Fang Ho, Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, No. 33, Linsen South Road, Zhongzheng District, Taipei, 100025, Taiwan, Tel +886 2 33668794, Fax +886 2 33668780, Email yfho@ntu.edu.twBackground: Easy and adequate access to community pharmacies is key to eliminating primary barriers to the utilization of medicines and healthcare services. The location of community pharmacies is important for patients and providers when choosing and opening a pharmacy, but only a handful of studies investigate factors associated with the geographical distribution of pharmacies. This study aimed to identify decisive factors for location selection when starting a pharmacy among districts/townships in Taiwan.Methods: This cross-sectional mixed mode study employed an explanatory sequential design, beginning with a quantitative analysis of national datasets, and followed by a qualitative analysis of structured interviews. The national data were extracted from the Taiwan government database of 2020, and the qualitative interviews were conducted with 10 community pharmacists through a snowball sampling in 2021. A multiple linear regression was conducted to identify salient predictors of the number of community pharmacies in each of the 368 districts/townships in Taiwan, including population density, median annual household income, number of physician offices, area, and proportion of female residents of each district/township. Ten chief pharmacists were interviewed to share viewpoints on the decision-making process of their selection of current pharmacy practice sites. Inductive thematic analysis was performed to extract factors pertinent to location selection for pharmacy operations and services.Results: Confirmed by quantitative and qualitative data, population density, numbers of physician offices, median annual household income, pharmacy operation type, and type of retail locations are key determinants for site selection in considering opening a new community pharmacy.Conclusion: The study uncovers salient factors associated with the choice of community pharmacy location in Taiwan and proposes the adequate number of physician offices that a community pharmacy can collaborate with. In addition, pharmacists should prudently consider if their preferred service features match the needs of residents.Keywords: community pharmacy, physician office, location, mixed mode

Olayinka O Shiyanbola,1 Martha A Maurer,2 Natasha Virrueta,1 Denise L Walbrandt Pigarelli,3 Yen-Ming Huang,4 Elizabeth J Unni,5 Paul D Smith6 1Division of Social and Administrative Sciences, School of Pharmacy, University of Wisconsin- Madison, Madison, WI, USA; 2Sonderegger Research Center, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA; 3Division of Pharmacy Practice, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA; 4Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei City, Taiwan; 5Department of Social, Behavioral, and Administrative Sciences, Touro College of Pharmacy, New York, NY, USA; 6Department of Family Medicine and Community Health, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USACorrespondence: Olayinka O Shiyanbola, Division of Social and Administrative Sciences, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI, 53705, USA, Tel +1 608 890 2091, Email Olayinka.Shiyanbola@wisc.eduPurpose: To assess the feasibility and acceptability of a health literacy-psychosocial support intervention – ADHERE and explore changes in glycemic values and medication adherence.Patients and Methods: Thirty-one participants with hemoglobin A1c (HbA1c) ≥ 8% were randomly allocated to control (usual care) or intervention groups (receiving usual care plus a 6-session pharmacist-led intervention focusing on the modifiable psychosocial factors that may influence medication adherence). Feasibility metrics evaluated recruitment, retention, and intervention adherence. Questionnaires were administered to collect psychosocial factors and self-reported medication adherence at baseline, the end of the intervention, 3 months, and 6 months post intervention. HbA1c values were extracted from electronic medical records. Repeated measures analysis of variance was used to compare differences in mean outcomes between the control and intervention groups. To assess intervention acceptability, eleven individuals participated in semi-structured interviews about their intervention experiences. Qualitative content analysis was used for analyzing the interviews.Results: Thirty participants completed the study. Overall, the findings support the feasibility of the intervention. There were significant differences in HbA1c values. Participants in the intervention group had lower A1C (8.3 ± 1.4) than in the control group (9.2 ± 1.3) at the time of 6-month follow-up (p = 0.003). In addition, the participants in the intervention group showed improved HbA1c at 6-month follow-up (8.3 ± 1.4), compared to baseline (9.4 ± 1.5, p = 0.011) and after 6-session intervention (8.9 ± 1.6, p = 0.046). However, there were no significant differences in medication adherence between groups over time. Qualitative themes suggest participants liked the intervention and perceived the additional support from the pharmacist as beneficial.Conclusion: A pharmacist-led intervention to provide additional health literacy-psychosocial support may contribute to long-term improvements in HbA1c. Equipping pharmacists with patient-specific diabetes medication adherence information and building in additional follow-up support for patients may improve patient health outcomes.Keywords: type 2 diabetes, medication adherence, health literacy, hemoglobin A1c, self-efficacy

Mei-Xiang Yu,1,* Xiao-Qin Ma,1,* Xin Song,2 Yong-Mei Huang,3 Hui-Ting Jiang,1 Jing Wang,1 Wan-Hua Yang1,4 1Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People’s Republic of China; 2South Campus, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201100, People’s Republic of China; 3Jinshan Hospital, Shanghai Fudan University School of Medicine, Shanghai 201508, People’s Republic of China; 4Department of Pharmacy, Ruijin Hospital North Affiliated to the Shanghai Jiao Tong University Medical School, Shanghai 201801, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wan-Hua Yang Email yangwanhuaxy@163.comBackground: Shenjin Huoxue Mixture (SHM), a classic traditional herb mixture has shown significant clinical efficacy against osteoarthritis (OA). Our previous experimental study has confirmed its anti–inflammatory and analgesic effect on acute soft tissue injury in rats, with the compound of glycyrrhizinate in SHM identified and the content of paeoniflorin in SHM determined by high-performance liquid chromatography (HPLC). However, the components and its pharmacological mechanisms of SHM against OA have not been systematically elucidated yet. Thus this study aimed to predict the key active ingredients and potential pharmacological mechanisms of SHM in the treatment of OA by network pharmacology approach and thin-layer chromatography (TLC) validation.Methods: The active ingredients of SHM and their targets, as well as OA-related targets, were identified from databases. The key active ingredients were defined and ranked by the number of articles retrieved in PubMed using the keyword “(the active ingredients [Title/Abstract]) AND Osteoarthritis[Title/Abstract] ”, and validated partially by TLC. The pharmacological mechanisms of SHM against OA were displayed by GO term and Reactome pathway enrichment analysis with Discovery Studio 3.0 software docking to testing the reliability.Results: Finally, 16 key active ingredients were identified and ranked, including quercetin validated through TLC. Inflammatory response, IL-6 signaling pathway and toll-like receptor (TLR) cascades pathway were predicted as the main pharmacological mechanisms of SHM against OA. Especially, 12 out of 16 key active ingredients, including validated quercetin, were well docked to IL-6 proteins.Conclusion: Our results confirmed the anti–inflammatory and analgesic effect of SHM against OA through multiple components, multiple targets and multiple pathways, which revealed the theoretical basis of SHM against OA and may provide a new drug option for treating OA.Keywords: Shenjin Huoxue Mixture, osteoarthritis, active ingredients, pharmacological mechanisms, network pharmacology, thin-layer chromatography

Yen-Ming Huang,1 Olayinka O Shiyanbola,1 Paul D Smith,2 Hsun-Yu Chan3 1Division of Social and Administrative Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA; 2Department of Family Medicine and Community Health, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA; 3Department of Psychology, Counseling, and Special Education, Texas A&M University-Commerce, Commerce, TX, USA Introduction: The Newest Vital Sign (NVS) is a survey designed to measure general health literacy whereby an interviewer asks six questions related to information printed on a nutritional label from an ice cream container. It enables researchers to evaluate several health literacy dimensions in a short period of time, including document literacy, comprehension, quantitative literacy (numeracy), application, and evaluation. No study has empirically examined which items belong to which latent dimensions of health literacy in the NVS using factor analysis. Identifying the factor structure of the NVS would enable health care providers to choose appropriate intervention strategies to address patients’ health literacy as well as improve their health outcomes accordingly. This study aimed to explore the factor structure of the NVS that is used to assess multiple dimensions of health literacy. Methods: A cross-sectional study administering the NVS in a face-to-face manner was conducted at two family medicine clinics in the USA. One hundred and seventy four individuals who participated were at least 20 years old, diagnosed with type 2 diabetes, prescribed at least one oral diabetes medicine, and used English as their primary language. Exploratory factor analysis and confirmatory factor analysis were conducted to investigate the factor structure of the NVS. Results: Numeracy and document literacy are two dimensions of health literacy that were identified and accounted for 63.05% of the variance in the NVS. Internal consistency (Cronbach’s alpha) of the NVS were 0.78 and 0.91 for numeracy and document literacy, respectively. Conclusion: Numeracy and document literacy appropriately represent the factor structure of the NVS and may be used for assessing health literacy in greater detail for patients with type 2 diabetes. Keywords: diabetes, health literacy, numeracy, document literacy, the Newest Vital Sign

Yen-Ming Huang,1 Olayinka O Shiyanbola,1 Paul D Smith2 1Division of Social and Administrative Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA; 2Department of Family Medicine and Community Health, University of Wisconsin-Madison, Madison, WI, USA Introduction: The exact pathway linking health literacy, self-efficacy, medication adherence, and glycemic control for type 2 diabetes remains unclear. Understanding the relationship between patient factors, medication adherence, and lower glycated hemoglobin (HbA1c) may help patients better manage their disease. This study examined the association of health literacy and medication self-efficacy with self-reported diabetes medication adherence, and the association of health literacy, medication self-efficacy, and self-reported diabetes medication adherence with HbA1c of patients with type 2 diabetes.Methods: This cross-sectional study utilized a face-to-face questionnaire at two family medicine clinics in a Midwestern state among 174 patients; subjects enrolled were at least 20 years old with diagnosed type 2 diabetes, prescribed at least one oral diabetes medicine, and understood English. Questionnaires were administered to assess the participants’: health literacy, using the Newest Vital Sign six-item questionnaire (NVS); self-efficacy for medication use, using the 13-item Self-Efficacy for Appropriate Medication Use Scale; and self-report medication adherence, using the eight-item Morisky Medication Adherence Scale. HbA1c values were obtained from participants’ electronic medical records. Multiple linear regressions were used to explore the association of health literacy and medication self-efficacy with both medication adherence and HbA1c level after controlling for all other covariates.Results: Self-reported health status (β = 0.17, p = 0.015) and medication self-efficacy (β = 0.53, p < 0.001) were positively associated with diabetes medication adherence. Health literacy was neither associated with diabetes medication adherence (β = -0.04, p = 0.586) nor HbA1c (β = -0.06, p = 0.542). Lower diabetes medication adherence (β = -0.26, p = 0.008) and higher number of prescribed medications (β = 0.28, p = 0.009) were correlated with higher HbA1c.Conclusion: Health literacy, as measured by the NVS, does not correlate with medication adherence or glycemic control among patients with type 2 diabetes. Interventions to improve patients’ self-efficacy of medication use may improve diabetes medication adherence. Keywords: diabetes, health literacy, medication adherence, medication self-efficacy

Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships. [ABSTRACT FROM AUTHOR]

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for multimodal postoperative pain management. We evaluated opioid-sparing effects and rehabilitative results after perioperative celecoxib administration for total knee arthroplasty.Methods: This was a prospective, randomized, observer-blind control study. Eighty patients that underwent total knee arthroplasty were randomized into two groups of 40 each. The study group received a single 400 mg dose of celecoxib, one hour before surgery, and 200 mg of celecoxib every 12 hours for five days, along with patient-controlled analgesic (PCA) morphine. The control group received only PCA morphine for postoperative pain management. Visual analog scale (VAS) pain scores, active range of motion (ROM), total opioid use and postoperative nausea/vomiting were analyzed.Results: Groups were comparable for age, pre-operative ROM, operation duration and intraoperative blood loss. Resting VAS pain scores improved significantly in the celecoxib group, compared with controls, at 48 hrs (2.13 +/- 1.68 vs. 3.43 +/- 1.50, p = 0.03) and 72 hrs (1.78 +/- 1.66 vs. 3.17 +/- 2.01, p = 0.02) after surgery. Active ROM also increased significantly in the patients that received celecoxib, especially in the first 72 hrs [40.8 degrees +/- 17.3 degrees vs. 25.8 degrees +/- 11.5 degrees , p = 0.01 (day 1); 60.7 degrees +/- 18.1 degrees vs. 45.0 degrees +/- 17.3 degrees , p = 0.004 (day 2); 77.7 degrees +/- 15.1 degrees vs. 64.3 degrees +/- 16.9 degrees , p = 0.004 (day 3)]. Opioid requirements decreased about 40% (p = 0.03) in the celecoxib group. Although patients suffering from post-operative nausea/vomiting decreased from 43% in control group to 28% in celecoxib group, this was not significant (p = 0.57). There were no differences in blood loss (intra- and postoperative) between the groups. Celecoxib resulted in no significant increase in the need for blood transfusions.Conclusion: Perioperative celecoxib significantly improved postoperative resting pain scores at 48 and 72 hrs, opioid consumption, and active ROM in the first three days after total knee arthroplasty, without increasing the risks of bleeding.Trial Registration: Clinicaltrials.gov NCT00598234. [ABSTRACT FROM AUTHOR]

Observational epidemiological studies have shown that a high consumption of lutein-containing foods is associated with decreased risk of chronic diseases. However, results are inconsistent, suggesting the possibility that confounders may impact serum lutein concentration after consumption. The present study aimed to determine the factors affecting serum lutein status and to characterize dynamic changes of lutein concentration in serum during lutein supplementation in healthy Chinese subjects. After baseline characteristics were determined, thirty-seven healthy participants were randomized to receive 6mg lutein/d, 12mg lutein/d, or placebo for 12 weeks, as well as to be observed for 6 additional weeks after the cessation of supplementation. Serum levels of lutein and beta-carotene were measured by HPLC at weeks 0, 1, 3, 6, 9, 12 and 18. Dietary intake was estimated by food-frequency questionnaires. No significant sex differences were found in serum concentration of lutein. Serum lutein level positively correlated with dietary lutein, retinol equivalents, vitamin C, vitamin E, beta-carotene and fat intake after adjustment for caloric intake, but not with BMI. After 12-weeks of supplementation, lutein levels increased approximately 1.8-fold and 2.3-fold for the 6-, and 12-mg dose groups respectively, approaching a plateau at week 9, and then decreased to baseline values at week 18. No adverse events or reductions in serum beta-carotene were observed throughout the study. Our findings indicate that increasing the consumption of lutein-rich fruit and vegetables can be considered as a long-term, sustainable and safe approach to reach and maintain high serum levels of lutein. [ABSTRACT FROM AUTHOR]

Aims: The effects of postprandial resistance and combined exercise on blood glucose profiles, particularly in patients with type 2 diabetes, remain unclear. Comprehending these responses may aid in diabetes management., Methods: Three trials were conducted: trial A examined aerobic, resistance, and combined exercise; trials B and C focused on three intensities of resistance and combined exercise. Participants including patients with type 2 diabetes and healthy adults completed a randomized crossover experiment with two arrangements of three interventions and continuous glucose monitoring. Blood glucose iAUC and slope were analyzed via repeated measures two-way ANOVA., Results: A total of 21 patients with type 2 diabetes (47.81±11.88 years) and 26 healthy adults (31.77±6.66 years) were assigned. In trials A-C, the main effect of subject group on iAUC/min was significant (p＜0.001, p = 0.003, and p＜0.001). The exercise in trial A (p = 0.006) and subject group in trial C (p = 0.005) significantly impacted the blood glucose slope., Conclusions: Resistance and combined exercise reduce postprandial hyperglycemia in type 2 diabetes patients. Monitoring glucose before exercise may help prevent extreme events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Aims: In the present study, we tested if terrestrially-derived humic substances (HS) could mitigate the adverse effects of elevated temperature and UVB radiation on the bacterial communities of two hard corals (Montipora digitata and Montipora capricornis), one soft coral (Sarcophyton glaucum), sediment and water. We also examined the impact of temperature, UVB radiation and HS supplementation on coral photosynthetic activity, a proxy for coral bleaching., Methods and Results: We performed a multifactorial experiment using a randomized-controlled microcosm setup. Coral photosynthetic efficiency was measured in vivo using a pulse amplitude modulation (PAM) fluorometer. Bacterial communities were analyzed using 16s rRNA gene sequencing. Corals in HS-supplemented microcosms had significantly higher photosynthetic activities than those in microcosms subjected to elevated temperature and UVB radiation. Additionally, HS supplementation significantly influenced the composition of sediment, water and host-associated bacterial communities. Reef organisms in HS supplemented microcosms contained distinct bacterial communities enriched with groups of potentially beneficial bacteria. In the hard coral Montipora digitata, we observed an interactive effect of HS supplementation, UVB radiation, and temperature., Conclusion: Our findings indicate that HS significantly modulates coral reef bacterial communities and support the hypothesis that these substances contribute to improved reef resistance to the adverse effects of elevated temperature and UVB radiation., (© The Author(s) 2025. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: A total of 100 patients diagnosed with mixed hemorrhoids from October 2022 to September 2023 in our hospital were randomly divided into groups by dice rolling and compared with the efficacy of different treatment options., Aim: To analyze the clinical effect and prognosis of mixed hemorrhoids treated with polidocanol injection combined with automatic elastic thread ligation operation (RPH)., Methods: A total of 100 patients with mixed hemorrhoids who visited our hospital from October 2022 to September 2023 were selected and randomly divided into the control group ( n = 50) and the treatment group ( n = 50) by rolling the dice. The procedure for prolapse and hemorrhoids (PPH) was adopted in the control group, while polidocanol foam injection + RPH was adopted in the treatment group. The therapeutic effects, operation time, wound healing time, hospital stay, pain situation (24 hours post-operative pain score, first defecation pain score), quality of life (QOL), incidence of complications (post-operative hemorrhage, edema, infection), incidence of anal stenosis 3 months post-operatively and recurrence rate 1 year post-operatively of the two groups were compared., Results: Compared with the control group, the total effective rate of treatment group was higher, and the difference was significant ( P < 0.05). The operation time/wound healing time/hospital stay in the treatment group were shorter than those in the control group ( P < 0.05). The pain scores at 24 hours after operation/first defecation pain score of the treatment group was significantly lower than those in the control group ( P < 0.05). After surgery, the QOL scores of the two groups decreased, with the treatment group having higher scores than that of the control group ( P < 0.05). Compared with the control group, the incidence of postoperative complications in the treatment group was lower, and the difference was significant ( P < 0.05); However, there was no significant difference in the incidence of postoperative bleeding between the two groups ( P > 0.05); There was no significant difference in the incidence of anal stenosis 3 months after operation and the recurrence rate 1 year after operation between the two groups ( P > 0.05)., Conclusion: For patients with mixed hemorrhoids, the therapeutic effect achieved by using polidocanol injection combined with RPH was better. The wounds of the patients healed faster, the postoperative pain was milder, QOL improved, and the incidence of complications was lower, and the short-term and long-term prognosis was good., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: We performed an umbrella review to synthesize evidence on the effects of physical activity (PA) interventions on indicators of physical and psychological health among children and adolescents, including body mass index (BMI), blood pressure (BP), depressive symptoms, and cognitive function., Methods: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched from inception through 31 July 2023. We included meta-analyses of randomized controlled trials exploring the effects of PA interventions on BMI, BP, depressive symptoms, or cognitive function in healthy or general children and adolescents. Standard Mean Difference (SMD) was calculated for continuous outcome indicators, while Relative Risk (RR) was calculated for categorical outcome indicators., Results: A total of 21 meta-analyses were included. The evidence for the effects of PA interventions on reducing BMI [n = 68,368, SMD = - 0.04, 95% confidence interval (CI) = - 0.07 to - 0.01, P = 0.012, I 2  = 46.6%], relieving diastolic BP (n = 8204, SMD = - 1.16, 95% CI = - 2.12 to - 0.20, P = 0.018, I 2  = 83.1%), preventing depressive symptoms (n = 5146, SMD = - 0.21, 95% CI = - 0.31 to - 0.12, P < 0.001, I 2  = 29.0%), and promoting cognitive function (n = 19,955, SMD = 0.40, 95% CI = 0.27-0.54, P < 0.001, I 2  = 88.0%) was all weak but significant (class IV evidence). Subgroup analyses demonstrated that school-based and after-school PA interventions, curricular PA interventions, and PA interventions emphasizing enjoyment were more effective in reducing BMI, while curricular PA and sports programs achieved greater executive function., Conclusion: PA interventions could weakly reduce BMI, relieve BP, prevent depressive symptoms, and promote cognitive function in general children and adolescents. Targeted interventions on PA should be a priority to promote physical and psychological health for children and adolescents, especially the curricular PA emphasizing enjoyment in the school settings., Competing Interests: Declarations. Conflict of interest: No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. Ethical approval: Not applicable., (© 2025. Children's Hospital, Zhejiang University School of Medicine.)

The storage and release of triacylglycerol (TAG) in lipid droplets (LDs) is regulated by dynamic protein interactions. α/β Hydrolase domain-containing protein 5 (ABHD5; also known as CGI-58) is a membrane/LD-bound protein that functions as a co-activator of patatin-like phospholipase domain-containing 2 (PNPLA2; also known as adipose triglyceride lipase) the rate-limiting enzyme for TAG hydrolysis. The dysregulation of TAG hydrolysis is involved in various metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). We previously demonstrated that ABHD5 interacted with PNPLA3, a closely related family member to PNPLA2. Importantly, a common missense variant in PNPLA3 (I148M) is the greatest genetic risk factor for MASLD. PNPLA3 148M functions to sequester ABHD5 and prevent coactivation of PNPLA2, which has implications for initiating MASLD; however, the exact mechanisms involved are not understood. Here, we demonstrate that LD targeting of both ABHD5 and PNPLA3 I148M is required for the interaction. Molecular modeling demonstrates important residues in the C terminus of PNPLA3 for LD binding and fluorescence cross-correlation spectroscopy demonstrates that PNPLA3 I148M has greater association with ABHD5 than WT PNPLA3. Moreover, the C terminus of PNPLA3 is sufficient for functional targeting of PNPLAs to LD and the interaction with ABHD5. In addition, ABHD5 is a general binding partner of LD-bound PNPLAs. Finally, PNPLA3 I148M targeting to LD is required to promote steatosis in vitro and in the liver. Overall results suggest that the interaction of PNPLA3 I148M with ABHD5 on LD is required to promote liver steatosis., Competing Interests: Conflict of interest J. W. P. is an Eli Lilly and Company employee and may own company stock or possess stock options. The other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Chemical investigation of the acid hydrolysate of Cynanchum bungei roots led to the isolation of eleven undescribed steroids, namely cynbungenins A-K (1-11), and seven previously described analogues (12-18). The complete structures of these compounds were elucidated using the comprehensive spectroscopic analyses and reference data. Structurally, compounds 1 and 2 represent the first example of androstane-type steroids found in the Cynanchum plants, and compounds 3-6 and 12 are characterized as pregnane-type steroids with a rare 8,14-seco-steroid core. In the cytotoxic activity assay, compound 16 displayed the strongest cytotoxic effect against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, with IC 50 values of 9.98-16.42 μM, and further research indicated that it induced both apoptosis and cell cycle arrest in the G0/G1 phase in a dose-dependent manner toward HepG2 cells., Competing Interests: Declaration of competing interest All authors declare that No conflict of interest exists., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to translate and validate the Adherence to Refills and Medications Scale into Traditional Chinese (ChARMS-T) and to investigate common barriers to medication adherence among patients with type 2 diabetes (T2D) in Taiwan., Methods: The ChARMS-T was developed through translation and application phases. During the translation phase, the scale underwent forward translation, backward translation, and cognitive debriefing. In the application phase, the finalized ChARMS-T was administered to patients with T2D at five Taiwan community pharmacies over eleven months starting in June 2023. Psychometric properties were assessed using criterion validity, construct validity through confirmatory factor analysis, and reliability through McDonald's omega., Results: A total of 343 participants completed surveys. Factor analysis of the 12-item ChARMS-T revealed two dimensions: medication-taking (8 items) and medication refill (4 items). The instrument demonstrated acceptable internal consistency, with McDonald's omega scores of 0.841 for medication-taking and 0.647 for medication refill. The medication refill subscale showed strong agreement with the objective refill measure, proportion of days covered, with a coefficient of 0.84, suggesting that these measures evaluate similar constructs. Evidence of known-groups validity was demonstrated by a significant difference between ChARMS-T scores and glycemic control ( p  = 0.047). Patients with good glycemic control had a significantly higher adherence rate to both refills and medication-taking compared to those with poor glycemic control. The most frequently reported barriers to medication-taking were carelessness (55.7%), forgetfulness (54.8%), and frequent dosing intervals (43.1%). For medication refills, 9.6% of the participants identified a lack of planning as the main reason for not refilling their diabetes medications on time, followed by forgetfulness (7.6%)., Conclusions: The ChARMS-T identified a broader range of non-adherence reasons and demonstrated good psychometric properties. It can be integrated into practice settings for screening and follow-up to enhance medication adherence through effective communication between healthcare professionals and patients, ultimately improving long-term patient health outcomes.

Ganoderma resinaceum is a traditional mushroom that contains natural products, including ergothioneine (EGT), which has powerful antioxidant properties in the human body. To increase EGT yield from G. resinaceum, the optimal carbon and nitrogen sources in the culture medium were determined as 20 g/L sucrose and 4 g/L NH4Cl, respectively. The fermentation conditions were then optimized using response surface methodology, with the highest EGT yield of approximately 4.10 mg/L achieved at an initial pH of 5.19, a culture medium volume of 118 mL, and a fermentation temperature of 26.90°C. After extraction, EGT was purified using Sephadex G-10, resulting in a purity of 43.72%. Both the crude and purified EGT extracts were evaluated for their inhibitory activity against xanthine oxidase in vitro, with positive results. These findings suggest the potential for developing edible fungi-derived medicines to treat gout, which could alleviate the side effects of traditional medicines.

The interaction between meiosis-expressed gene 1 (MEIG1) and Parkin co-regulated gene (PACRG) is a critical determinant of spermiogenesis, the process by which round spermatids mature into functional spermatozoa. Disruption of the MEIG1-PACRG complex can impair sperm development, highlighting its potential as a therapeutic target for addressing male infertility or for the development of non-hormonal contraceptive methods. This study used virtual screening, molecular docking, and molecular dynamics (MD) simulations to identify small molecule inhibitors targeting the MEIG1-PACRG interface. MD simulations provided representative protein conformations, which were used to virtually screen a library of over 800,000 compounds, resulting in 48 high-ranking candidates for each protein. PACRG emerged as a favorable target due to its flexible binding pockets and better docking scores compared to MEIG1. Key binding residues with compounds included W50, Y68, N70, and E74 on MEIG1, and K93, W96, E101, and H137 on PACRG. MD simulations revealed that compound stability in MEIG1 complexes is primarily maintained by hydrogen bonding with E74 and π-π stacking interactions with W50 and Y68. In PACRG complexes, compound stabilization is facilitated by hydrogen bonding with E101 and π-π interactions involving W96 and H137. These findings highlight distinct molecular determinants of ligand binding for each protein. Our work provides mechanistic insights and identifies promising compounds for further experimental validation, establishing a foundation for developing MEIG1-PACRG interaction inhibitors as male contraceptives.

Aims: Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application., Methods: In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II., Results: We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13)., Conclusion: Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function., Competing Interests: The authors report grants from the National Key Research and Development Program of China (No. 2022YFA1104300), the National Nature Science Foundation of China (No. 82270302, 82260173, 81970256), the Key Research Project (No. 20192BBH80015, 20202BBG73028), and the Project for Leading Talent of department of science and technology, Jiangxi Province (No. 20204BCJ22035, 20212BDH81020), all related to this study., (© 2024 Huang et al.)

Herein a catalyst-free solvent-controlled method for the divergent synthesis of spirocyclopropyl and spiropyrazoline oxindoles from 3-ylideneoxindoles and ethyl diazoacetate was developed. With ClCH 2 CH 2 Cl as the solvent, spirocyclopropyl oxindoles were obtained in moderate to excellent yields, whereas the use of MeOH as solvent afforded spiropyrazoline oxindoles in moderate to good yields. The readily available substrates, simple operation and various product transformations further highlighted the utility of this method., (© 2024 Wiley-VCH GmbH.)

The THαβ host immunological pathway contributes to the response to infectious particles (viruses and prions). Furthermore, there is increasing evidence for associations between autoimmune diseases, and particularly type 2 hypersensitivity disorders, and the THαβ immune response. For example, patients with systemic lupus erythematosus often produce anti-double stranded DNA antibodies and anti-nuclear antibodies and show elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 throughout the disease course. These cytokines and antibody isotypes are associated with the THαβ host immunological pathway. Similarly, the type 2 hypersensitivity disorders myasthenia gravis, Graves' disease, graft-versus-host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjögren's syndrome have also been linked to the THαβ pathway. Considering the potential associations between these diseases and dysregulated THαβ immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferon α/β could be explored for effective management.

Objectives: Second-generation antipsychotics (SGAs) are often prescribed for patients with schizophrenia; however, SGAs are associated with the risk of metabolic syndrome (MetS). This study aimed to investigate the clinical and biochemical determinants of SGA-related MetS., Methods: Patients with schizophrenia, aged between 20 and 65 years, and under clozapine or olanzapine treatment for at least 9 months, were recruited from a mental hospital. Demographic, comorbidity, clinical status, laboratory, and drug regimen data were collected through chart review. Circulating levels of adiponectin, thyroid hormone responsive protein, and fatty acid binding protein 4 (FABP4) were assayed. Multiple logistic regression was used to identify risk predictors of MetS., Results: A total of 176 participants were enrolled, including 138 (78.4 %) clozapine users and 38 (21.6 %) olanzapine users. Forty-five (25.6 %) patients were classified as having MetS. The duration of clozapine or olanzapine usage was significantly shorter in those with MetS (p=0.026) than those without MetS. Patients with MetS had a significantly higher serum FABP4 concentration than their counterparts (22.5 ± 8.8 ng/mL vs. 15.7 ± 6.7 ng/mL, p<0.001), and also a significantly lower adiponectin level (6.9 ±4.0 mg/mL vs. 11.6 ± 6.6 mg/mL, p<0.001). A FABP4 level ≥ 16.98 ng/mL (OR: 24.16, 95 % CI: 7.47-78.09, p<0.001) was positively correlated with MetS, whereas serum adiponectin level was inversely correlated with MetS (OR: 0.7980, 95 % CI: 0.70-0.90, p<0.001)., Conclusions: Adiponectin, FABP4, and certain clinical covariates and comedications were highly correlated with SGA-related MetS. Further studies are required to investigate the underlying mechanisms., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Testicular torsion-detorsion damage is a common ischemia-reperfusion injury brought on by an excess of reactive oxygen species. Reactive oxygen species may affect cellular differentiation by regulating gene expression. The heat shock protein 70-2 (HSP70-2) gene expression in the testis is essential for spermatogenesis. Safranal, the main bioactive ingredient isolated from Crocus sativus L., has potent antioxidant properties. Our current investigation examined the potential mechanism by which safranal could shield the testis from ischemia-reperfusion damage., Methods: Sixty Sprague-Dawley male rats were randomly assigned into the sham-operated control group, testicular ischemia-reperfusion group, and safranal-treated group. Testicular ischemia was achieved by twisting the left testis 720° counterclockwise and maintained for two hours. Reperfusion was created by counter-rotating the torsional left testis to its natural position. Rats in the safranal-treated group received an intraperitoneal injection of safranal at the onset of reperfusion. Testes were excised to examine the quantity of malondialdehyde (a sensitive indicator of reactive oxygen species), expression of the HSP70-2 protein, and the testicular spermatogenic activity., Results: Unilateral testicular ischemia-reperfusion significantly increased the levels of malondialdehyde in the ipsilateral testes compared to the control group. It also significantly reduced the expression of HSP70-2 protein and spermatogenic activity ( p < 0.001). In addition, our investigation revealed that, in comparison to the testicular ischemia-reperfusion group, the ipsilateral testes of the safranal-treated group had significantly lower levels of malondialdehyde and had significantly higher HSP70-2 expression and levels of spermatogenic function ( p < 0.01)., Conclusions: These results suggest that via lowering reactive oxygen species levels and increasing HSP70-2 expression, safranal protects against testicular torsion/detorsion-induced ischemia/reperfusion injury., Competing Interests: The authors declare no conflict of interest., (©2024 The Author(s). Published by MRE Press.)

Previous studies on disease in coral reef organisms have neglected the natural distribution of potential pathogens and the genetic factors that underlie disease incidence. This study explores the intricate associations between hosts, microbial communities, putative pathogens, antibiotic resistance genes (ARGs) and virulence factors (VFs) across diverse coral reef biotopes. We observed a substantial compositional overlap of putative bacterial pathogens, VFs and ARGs across biotopes, consistent with the 'everything is everywhere, but the environment selects' hypothesis. However, flatworms and soft corals deviated from this pattern, harbouring the least diverse microbial communities and the lowest diversity of putative pathogens and ARGs. Notably, our study revealed a significant congruence between the distribution of putative pathogens, ARGs and microbial assemblages across different biotopes, suggesting an association between pathogen and ARG occurrence. This study sheds light on the existence of this latent pathobiome, the disturbance of which may contribute to disease onset in coral reef organisms., (© 2024 John Wiley & Sons Ltd.)

Background and Objectives: Accumulating pediatric efficacy and safety data on drug use is inherently challenging yet essential. This study aimed to analyze the frequency and compute the odds of pediatric drug-associated liver injury across age groups (early childhood, middle childhood, and adolescence) and therapeutic categories using adverse drug reactions (ADRs) reporting data spanning nearly two decades., Methods: We analyzed the reports of suspected ADRs occurring in children and adolescents in the Taiwan National Adverse Drug Reaction Reporting System during the period from May 1998 until July 2017. Standardized Medical Dictionary for Regulatory Activities Queries were utilized to identify suspected hepatic ADRs. Outcome patterns across age groups were compared using the chi-squared test, and disproportionality analysis was employed to calculate reporting odds ratios (RORs) of hepatic versus nonhepatic reports., Results: Among 16,673 reports, 484 (2.9%) were identified as suspected hepatic ADRs, involving 193 distinct drugs. The mean age of affected individuals was 8.2 years. Outcome types in adolescents were predominantly serious (91.8%). Antibacterials for systemic use (18.8%) and antiepileptics (8.7%) were the most frequently implicated therapeutic categories. Drugs with high ADR occurrence rates and significant RORs included oxacillin (5.2%; ROR: 12.07), methotrexate (4.1%; ROR: 9.07), and phenobarbital (2.7%; ROR: 5.04). Some medications exhibited higher ratios of used-versus-recommended doses, suggesting inappropriate dosing., Conclusions: Pediatric drug-associated liver injury was not uncommon and may result in serious outcomes. This study underscores the need for heightened vigilance in administering certain high-risk drugs and attentiveness in proper dosing for children, including adolescents., Competing Interests: Declarations. Funding: This study was funded by the National Science and Technology Council, Executive Yuan, Taipei, Taiwan, R.O.C. (NSTC 113-2320-B-002-051) and supported by the National Taiwan University School of Pharmacy Alumni Association in North America. The funder/sponsor did not participate in the work. Conflicts of Interest: The authors declare no conflicts of interest. Ethics Approval: The local ethics committee approved the study (NTUH REC 202407169RINA). Data Availability Statement: The datasets in the current study are available from the corresponding author upon reasonable request. Code Availability: Not applicable. Author Contributions: Y.T.H. designed the study, performed data analysis, and drafted the initial manuscript. Y.M.H. designed the study, interpreted study findings, and revised the manuscript. N.C.L. interpreted the results and reviewed and revised the manuscript. P.I.L. conceptualized the study, interpreted the results, and reviewed and revised the manuscript for important intellectual content. Y.F.H. conceptualized and designed the study, supervised data collection and analysis, and drafted and finalized the manuscript. All authors contributed to and approved the final manuscript., (© 2025. The Author(s).)

Oral squamous cell carcinoma (OSCC) is a type of head and neck cancer (HNC) with a high recurrence rate, which has been reported to be associated with the presence of cancer stem cells (CSCs). Tribbles pseudokinase 3 (TRIB3) is involved in intracellular signaling and the aim of the present study was to investigate the role of TRIB3 in the maintenance of CSCs. Analysis of The Cancer Genome Atlas database samples demonstrated a positive correlation between TRIB3 expression levels and shorter overall survival rates in patients with HNC. Knockdown of TRIB3 in the SAS and HSC-3 OSCC cell lines reduced cell proliferation through the induction of cell cycle arrest, but not of apoptosis. The population of OSCC-CSCs, defined by a high level of intracellular aldehyde dehydrogenase activity and the ability to form tumorspheres, was also reduced in TRIB3-silenced OSCC cells. The tumorigenicity of tumorspheres derived from the SAS OSCC cell line was reduced following TRIB3 knockdown. These results suggested the potential involvement of TRIB3 in the self-renewal capability of the OSCC CSCs. Mechanistically, TRIB3 was shown to positively regulate SOX2 expression via maintaining both the protein expression level and the SOX2 promoter-binding capability of E2F transcription factor 1 (E2F1). Additionally, TRIB3 also increased the expression level of EGFR through preventing its lysosomal degradation. The significant associations between TRIB3 and E2F1, SOX2 or EGFR expression were also confirmed using a HNC tissue array. Taken together, the findings of the present study may suggest that TRIB3 is an oncogenic protein that supports the stemness of OSCC and that targeting TRIB3 may be a potential strategy for OSCC therapy in the future.