Identification of anti-fibrotic and pro-apoptotic bioactive compounds from Ganoderma formosanum and their possible mechanisms in modulating TGF-ß1-induced lung fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits of Ganoderma sinense particularly in addressing pulmonary-related ailments. Ganoderma formosanum, an indigenous subspecies of G. sinense from Taiwan, has demonstrated the same therapeutic properties. AIM OF THE STUDY: The aim of this study is to identify bioactive compounds and evaluate the potential of G. formosanum extracts as a novel treatment to alleviate pulmonary fibrosis (PF). Using an in-house drug screening platform, two-stage screening was performed to determine their anti-fibrotic efficacy. METHODS AND MATERIALS: G. formosanum was fractionated into four partitions by solvents of different polarities. To determine their antifibrotic and pro-apoptotic properties, the fractions were analyzed using two TGF-ß1-induced pulmonary fibrosis cell models (NIH-3T3) and human pulmonary fibroblast cell lines, immunoblot, qRT-PCR, and annexin V assays. Subsequently, transcriptomic analysis was conducted to validate the findings and explore possible molecular pathways. The identification of potential bioactive compounds was achieved through UHPLC-MS/MS analysis, while molecular interaction study was investigated by multiple ligands docking and molecular dynamic simulations. RESULTS: The ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-ß1-induced fibrotic models. Moreover, the EAF exhibited no discernible cytotoxicity. Untargeted UHPLC-MS/MS analysis identified potential bioactive compounds in EAF, including stearic acid, palmitic acid, and pentadecanoic acid. Multiple ligands docking and molecular dynamic simulations further confirmed that those bioactive compounds possess the ability to inhibit TGF-ß receptor 1. CONCLUSION: Potential bioactive compounds in G. formosanum were successfully extracted and identified in the EAF, whose anti-fibrotic and pro-apoptotic properties could potentially modulate pulmonary fibrosis. This finding not only highlights the EAF's potential as a promising therapeutic candidate to treat pulmonary fibrosis, but it also elucidates how Ganoderma confers pulmonary health benefits as described in the ancient texts.

Comparison of the effectiveness of local anesthesia for the digital block between single-volar subcutaneous and double-dorsal finger injections: a systematic review and meta-analysis of randomized control trials.

Local anesthesia is an effective method to perform digital nerve blocks. In this study, we compare the effectiveness of single-volar subcutaneous and double-dorsal injection through a systematic review and meta-analysis of randomized controlled trials (RCTs). A systematic search of PubMed, Embase, and the Cochrane Library from inception to 7 April 2021 was performed. RCTs with the effects of single-volar subcutaneous and double-dorsal injection were eligible. Meta-analysis was performed using random effect models with pooled standardized mean differences (SMDs) and 95% confidence intervals (CI). RoB 2.0 and GRADE of Recommendation Assessment, Development, and Evaluation criteria were applied for evaluating the bias. A total of 2484 studies were initially identified, with 11 eligible RCTs finally included in the meta-analysis (1363 patients). The pooled data of nine studies showed single-volar injection had a statistically significantly lower pain score (pooled SMD: 0.20, 95% CI, 0.01 to 0.39, p = 0.041, I2 = 58%, N = 1187) and higher patient preference but invalid anesthesia at the dorsal proximal digit. No significant differences were observed in the onset of anesthesia, adjacent digit invalid numbness, distal phalanx invalid anesthesia, additional injection rate, and adverse effects. In conclusion, this meta-analysis of RCTs showed that the single-volar injection was associated with a lower pain sensation during injection and higher patient satisfaction with a reduced anesthetic effect over the proximal dorsal phalanx. Further high-quality RCTs with a higher number of cases are needed to validate our results.

Developing an Integrated Electronic Medication Reconciliation Platform and Evaluating its Effects on Preventing Potential Duplicated Medications and Reducing 30-Day Medication-Related Hospital Revisits for Inpatients.

The aims were to develop an integrated electronic medication reconciliation (ieMR) platform, evaluate its effects on preventing potential duplicated medications, analyze the distribution of the potential duplicated medications by the Anatomical Therapeutic and Chemical (ATC) code for all inpatients, and determine the rate of 30-day medication-related hospital revisits for a geriatric unit. The study was conducted in a tertiary medical center in Taiwan and involved a retrospective quasi pre-intervention (July 1-November 30, 2015) and post-intervention (October 1-December 31, 2016) study design. A multidisciplinary team developed the ieMR platform covering the process from admission to discharge. The ieMR platform included six modules of an enhanced computer physician order entry system (eCPOE), Pharmaceutical-care, Holistic Care, Bedside Display, Personalized Best Possible Medication Discharge Plan, and Pharmaceutical Care Registration System. The ieMR platform prevented the number of potential duplicated medications from pre (25,196 medications, 2.3%) to post (23,413 medications, 3.8%) phases (OR 1.71, 95% CI, 1.68-1.74; p < .001). The most common potential duplicated medications classified by the ATC codes were cardiovascular system (28.4%), alimentary tract and metabolism (26.4%), and nervous system (14.9%), and by chemical substances were sennoside (12.5%), amlodipine (7.5%), and alprazolam (7.4%). The rate of medication-related 30-day hospital revisits for the geriatric unit was significantly decreased in post-intervention compared with that in pre-intervention (OR = 0.12; 95% CI, 0.03-0.53; p < .01). This study indicated that the ieMR platform significantly prevented the number of potential duplicated medications for inpatients and reduced the rate of 30-day medication-related hospital revisits for the patients on the geriatric unit.

Effects of Socioeconomic Status on Alzheimer Disease Mortality in Taiwan.

OBJECTIVE: The combined effects of individual and neighborhood socioeconomic status (SES) on survival rates of patients with Alzheimer's disease (AD) remain unclear. DESIGN: Retrospective cohort study. SETTING: National Health Insurance Bureau of Taiwan data (2003-2012). PARTICIPANTS: Patients with AD. MEASUREMENTS: The authors aimed to analyze the effects of neighborhood and individual SES on the 5-year survival rates of patients with AD. The author defined individual and neighborhood SES based on income-related insurance payment amounts and residence in advantaged versus disadvantaged areas and compared survival rates using the Cox proportional hazards model after adjusting for risk factors. RESULTS: A total of 1,754 patients with AD were identified. Each patient was followed for 5 years or censored. The 5-year overall survival rates were worst for those with a low individual SES in a disadvantaged area. After adjustment for sex, age, and comorbidities, patients with a low individual SES living in disadvantaged areas had the worse survival rate than those with a high SES (hazard ratio: 2.19; 95% confidence interval [CI]: 1.53-3.13). In contrast, after the adjustment for characteristics, patients with a high individual SES in disadvantaged areas had a similar mortality rate to those with a high individual SES in advantaged areas (hazard ratio: 0.93; 95% CI: 0.64-1.35). CONCLUSION: Despite universal health coverage, patients with AD and a low individual SES in disadvantaged areas exhibited the worst survival rate. The socioeconomic survival gradient among patients with AD in Taiwan may result from differences in major attributes of individual and neighborhood SES.

Age-related changes of task-specific brain activity in normal aging.

An important question in healthcare for older patients is whether age-related changes in cortical reorganization can be measured with advancing age. This study investigated the factors behind such age-related changes, using time-frequency analysis of event-related potentials (ERPs). We hypothesized that brain rhythms was affected by age-related changes, which could be reflected in the ERP indices. An oddball task was conducted in two experimental groups, namely young participants (N=15; mean age 23.7±2.8 years) and older participants (N=15; mean age 70.1±7.9 years). Two types of stimuli were used: the target (1 kHz frequency) and standard (2 kHz frequency). We scrutinized three ERP indices: event-related spectral power (ERPSP), inter-trial phase-locking (ITPL), and event-related cross-phase coherence (ERPCOH). Both groups performed equally well for correct response rate. However, the results revealed a statistically significant age difference for inter-trial comparison. Compared with the young, the older participants showed the following age-related changes: (a) power activity decreased; however, an increase was found only in the late (P3, 280-450 ms) theta (4-7 Hz) component over the bilateral frontal and temporo-frontal areas; (b) low phase-locking in the early (N1, 80-140 ms) theta band over the parietal/frontal (right) regions appeared; (c) the functional connections decreased in the alpha (7-13 Hz) and beta (13-30 Hz) bands, but no difference emerged in the theta band between the two groups. These results indicate that age-related changes in task-specific brain activity for a normal aging population can be depicted using the three ERP indices.