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Taiwan has implemented a Medical Home Healthcare (MHHC) policy to provide home healthcare services to residents in need. First was the Ordinary Medical Home Healthcare (OMHHC) program in 1997 and then expanded to Integrated Medical Home Healthcare (IMHHC) in 2016. The OMHHC is provided care for residents with tubes at home or in institutions by physicians and nurses, and the IMHHC include additional professions, such as pharmacists and dentists. This study analyzed the longitudinal data from 2013 to 2020 with respect to overall home health services utilizations, and the type of services, and compared the differences between areas with and without healthcare shortages. Our results showed that the IMHHC program enhanced the accessibility of home healthcare to those in needs, especially those in healthcare shortage areas. However, some services in the IMHHC program may still have low utilization rates. It is necessary to investigate the potential barriers for residents to access those services., Competing Interests: Declaration of competing interest The authors declared no conflict of interests., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: The effectiveness of fish oil in preventing cardiovascular events is still debating. Some studies indicate a correlation between the use of fish oil supplements and reduced mortality or decreased incidence of stroke. However, other studies show no significant association between fish oil intake and stroke prevention, indicating an ongoing debate. This study aimed at exploring which subjects may benefit more from fish oil supplementation., Methods: This study utilized the data obtained through face-to-face interview from the Taiwan Longitudinal Study in Aging (TLSA). A total of 3,652 participants were included from the 2003 baseline data, after excluding patients with pre-existing ischemic heart disease or stroke. Participants were divided into two groups based on whether taking fish oil supplement or not. Participants were followed until 2015, estimating and comparing the all-cause mortality and cumulative incidence rate of stroke between both groups., Results: The results of the 12-year longitudinal study showed that the cumulative incidence rate of stroke in the fish oil supplementation group was 5.7%, compared to 7.7% in the non-supplemented group (P < 0.05). Additionally, the crude hazard ratio for stroke was significantly lower in the fish oil supplementation group (HR = 0.686;95% CI 0.476-0.987). However, after adjusting potential confounders, the adjusted risk of stroke was lower only for the diabetic patients supplemented with fish oil (aHR = 0.123; 95% CI 0.016-0.930) compared to non-diabetic patients (aHR = 0.917; 95% CI 0.616-1.364)., Conclusion: This study suggests that there is an association between fish oil supplementation and a lower cumulative incidence rate of subsequent stroke among diabetic patients., (© 2024. The Author(s).)

Background: The efficacy of adjuvant sublingual immunotherapy (SLIT) in correcting structural problems in patients with allergic rhinitis (AR) caused by mite who have undergone septomeatoplasty (SMP) has not been studied., Methods: This non-randomized controlled study recruited patients with AR (caused by mite) and concurrent septal deviation and inferior turbinate hypertrophy, at a tertiary hospital in Taiwan. SMP was performed on all patients as a surgical intervention. The patients were then divided into two groups: the control group, which underwent surgery only, and the experimental group, which received SLIT as an adjuvant treatment. Demographic data and rhinitis control assessment test (RCAT) results were analyzed., Results: A total of 96 patients were enrolled in the study (SMP + SLIT group, n = 52; SMP only group, n = 44). No significant differences were observed in any of the variables between the two groups before and one month after surgery. However, during evaluations at the third and sixth month, the SMP + SLIT group showed significant improvement in the total RCAT scores compared to the SMP only group (28.6 ± 1.56 vs. 24.5 ± 3.66, p < 0.001; 27.1 ± 2.87 vs. 19.9 ± 5.56, p < 0.001). In addition, significantly better control of all RCAT sub-categories was observed in the SMP + SLIT group at the third and sixth month evaluations., Conclusions: SLIT may serve as an ideal adjuvant therapy after SMP in patients with AR., Level of Evidence: 3 Laryngoscope, 134:3073-3079, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Various diseases involving the cavernous sinus can cause a condition called cavernous sinus syndrome (CSS), which is characterized by ophthalmoplegia or sensory deficits over the face resulting from the compression effect of internal structure. While tumor compression is the most reported cause of CSS, statistical data on CSS caused by infections are limited. Its risk factors, treatment methods, and clinical outcomes are not well-documented. Methods: In this retrospective study, we reviewed the data of patients admitted to a tertiary medical center from 2015 to 2022 with a diagnosis of acute and chronic sinusitis and at least one diagnostic code for CSS symptoms. We manually reviewed whether patients were involved in two or more of the following cranial nerves (CN): CN III, CN IV, CN V, or CN VI, or at least one of these nerves with a neuroimaging-confirmed lesion in the cavernous sinus. Results: Nine patients were diagnosed with rhinosinusitis-related CSS. The most common comorbidity was type 2 diabetes, and the most common clinical manifestations were diplopia and blurred vision. The sphenoid sinus was the most affected sinus. One patient expired due to a severe brain abscess infection without surgery. The remaining patients underwent functional endoscopic sinus surgery, and 50% of the pathology reports indicated fungal infections. Staphylococcus spp. was the most cultured bacteria, and Amoxycillin/Clavulanate was the most used antibiotic. Only four patients had total recovery during the follow-up one year later. Conclusions: CSS is a rare but serious complication of rhinosinusitis. Patients with diabetes and the elderly may be at a higher risk for this complication. Even after treatment, some patients may still have neurological symptoms.

Objectives: Chronic rhinosinusitis (CRS) reduces the health-related quality of life and subsequently causes a tremendous socio-economic impact. Although many studies have been conducted, few have identified a relationship between bacteriological characteristics and different phenotypes or endotypes. Therefore, this study aimed to elucidate the recent trends in bacterial cultures from different types of CRS in the Asian population., Methods: This retrospective case-control study recruited patients diagnosed with CRS who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into those with chronic rhinosinusitis with nasal polyps (CRSwNP)/chronic rhinosinusitis without nasal polyps (CRSsNP), eosinophilic chronic rhinosinusitis (eCRS)/non-eosinophilic chronic rhinosinusitis (NECRS), and central compartment atopic disease (CCAD)/lateral-dominant nasal polyp (LDNP) groups. The demographic data and bacteriological characteristics of the groups were analyzed., Results: We included 503 patients, identifying no significant difference between CRSwNP and CRSsNP for several common bacteria in CRS. The number of Staphylococcus epidermidis isolates in culture was significantly higher in the NECRS group (50.46% vs. 32.56%, p = 0.0003) than that in the eCRS group. The number of methicillin-resistant Staphylococcus aureus (MRSA; 8.51% vs. 2.35%, p = 0.0221) positive isolates was significantly higher in the CCAD group than that in the LDNP group., Conclusions: This was the first study in Asia to analyze the relationship between bacteriological characteristics and CCAD. MRSA is significantly higher in the CCAD group than that in the LDNP group. Recognizing the unique microbiology of CRSwNP, eCRS, and CCAD is crucial when selecting antimicrobial therapy to lessen the socio-economic impact., Level of Evidence: 3 Laryngoscope, 134:1071-1076, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Indole-3-acetic acid (IAA), a protein-bound uremic toxin resulting from gut microbiota-driven tryptophan metabolism, increases in hemodialysis (HD) patients. IAA may induce endothelial dysfunction, inflammation, and oxidative stress, elevating cardiovascular and cognitive risk in HD patients. However, research on the microbiome-IAA association is limited. This study aimed to explore the gut microbiome's relationship with plasma IAA levels in 72 chronic HD patients aged over 18 (August 2016-January 2017). IAA levels were measured using tandem mass spectrometry, and gut microbiome analysis utilized 16s rRNA next-generation sequencing. Linear discriminative analysis effect size and random forest analysis distinguished microbial species linked to IAA levels. Patients with higher IAA levels had reduced microbial diversity. Six microbial species significantly associated with IAA levels were identified; Bacteroides clarus , Bacteroides coprocola , Bacteroides massiliensi , and Alisteps shahii were enriched in low-IAA individuals, while Bacteroides thetaiotaomicron and Fusobacterium varium were enriched in high-IAA individuals. This study sheds light on specific gut microbiota species influencing IAA levels, enhancing our understanding of the intricate interactions between the gut microbiota and IAA metabolism.

Objectives: The primary aim was to determine the prevalence of gastrointestinal diseases in patients with chronic rhinosinusitis (CRS), utilizing the National Health Insurance Research Database (NHIRD) in Taiwan. Several studies have supported the existence of distinct immune patterns between the Asian and Western populations in CRS patients. Through the population-based case-control study, we could compare the differences between various regions and provide further treatment strategies for subsequent studies in Asian CRS patients. The secondary aim was to assess whether different types of CRS influence the correlation with specific GI diseases. Understanding how different phenotypes or endotypes of CRS may relate to distinct GI disease patterns could provide valuable insights into the underlying mechanisms and potential shared pathways between these conditions. Methods: We use the NHIRD in Taiwan. Newly diagnosed patients with CRS were selected between January 1, 2001 and December 31, 2017 as the case group, and the controls were defined as individuals without a history of CRS. Patients with CRS were divided into two groups: with nasal polyps and without nasal polyps. We also separated GI tract diseases into four groups based on their different pathophysiologies. Results: This study included 356,245 participants (CRS: 71,249 and control: 284,996). The results showed that CRS was significantly associated with some specific GI tract diseases, including acute/chronic hepatitis B, gastroesophageal reflux disease (GERD) with/without esophagitis, achalasia of cardia, peptic/gastrojejunal ulcer, Crohn's disease, and ulcerative colitis. In addition, when CRS was subcategorized into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP), GERD with esophagitis and peptic ulcer were significantly associated with CRSsNP. Conclusions: A significant association between CRS and premorbid GI tract diseases has been identified. Remarkably, GERD with esophagitis and peptic ulcer were significantly associated with CRSsNP. The underlying mechanisms require further investigation and may lead to new treatments for CRS. Researchers can further investigate the mechanisms by referring to our classification method to determine the implications for diagnosis and treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Fatigue is a common symptom after a traumatic brain injury (TBI) and may persist for weeks or years. However, nonpharmacological management strategies for fatigue alleviations are almost nonexistent; thus, effective fatigue management programs are needed urgently., Purposes: We aimed to evaluate the effects of self-administered acupressure programs on post-TBI fatigue and heart rate variability and identify the possible correlation between the improvements in fatigue symptoms and the changes in heart rate variability., Design: This randomized controlled trial included 2-point acupressure (TPA; n = 27), 5-point acupressure (FPA; n = 27), and usual care (UC, control; n = 27) groups who underwent several assessments before and after the study intervention. Heart rate variability was evaluated at baseline, weeks 2 and 3, and treatment completion., Methods: The TPA and FPA groups self-administered acupressure (3 minutes per acupoint; bilateral), thrice daily for 4 weeks, whereas the UC group received routine treatment without acupressure., Results: Both the TPA and FPA groups exhibited substantial improvements in fatigue symptoms compared with the baseline findings in the UC group. In addition, the TPA and FPA groups exhibited increased high-frequency power and mean number of times per hour in which the changes in successive normal sinus intervals (RR) gradually exceeded 50 ms (pNN50). Changes in high-frequency power and pNN50 were correlated with improvements in post-TBI fatigue symptoms., Conclusion: Acupressure may alleviate chronic fatigue and enhance parasympathetic activity in TBI survivors. The enhancement of parasympathetic activity may be correlated with improvements in post-TBI fatigue symptoms., Relevance to Clinical Practice: Healthcare providers should incorporate self-administered acupressure into the care plans for TBI survivors to improve their fatigue symptoms., Competing Interests: The authors declare no conflicts of interests., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Perfluoroalkyl substances (PFAS) have been reported to be harmful to multiple organs in the human body. Based on a previous study suggesting that hemodialysis (HD) may be a means of eliminating PFAS from the human body, we aimed to compare the serum PFAS concentrations of patients undergoing regular HD, patients with chronic kidney disease (CKD) and controls. Additionally, we also investigated the correlation between PFAS and biochemical data, as well as concurrent comorbidities. We recruited 301 participants who had been on maintenance dialysis for >90 days, 20 participants with stage 5 non-dialysis CKD, and 55 control participants who did not have a diagnosis of kidney disease, with a mean creatinine level of 0.77 mg/dl. Eight different PFAS, namely perfluorooctanoic acid (PFOA), total and linear perfluorooctanesulfonic acid (PFOS), perfluoroheptanoic acid (PFHpA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Spearman correlation and multivariable linear regression with 5 % false discovery rate were used to evaluate the relationships between PFAS and clinical parameters in HD patients and controls. Circulating concentrations of seven PFAS, including total and linear PFOS (T-PFOS and L-PFOS) PFDA, PFNA, PFHxS, PFOA, and PFUnDA, were significantly lower in the HD group compared to the CKD and control group. For the interplay between biochemical data and PFAS, all of the studied PFAS were positively correlated with aspartate aminotransferase, alanine aminotransferase, glucose, blood urea nitrogen, ferritin, and vitamin D in the controls, while in HD patients, the PFAS were all positively correlated with albumin, uric acid, iron, and vitamin D. These findings may offer valuable insights for future studies seeking to eliminate PFAS., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: The prevalence of eosinophilic chronic rhinosinusitis (ECRS) has increased in Taiwan with a higher recurrence rate of nasal polyps after surgery. Therefore, we aimed to formulate the pre-operative diagnostic criteria for patients with ECRS in Taiwan., Methods: This case-control study included patients diagnosed with CRS with nasal polyps (CRSwNP) who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into ECRS and non-eosinophilic CRS (NECRS) groups based on their histopathology. Demographic data, symptom severity scores, and computed tomography findings of the two groups were analyzed. We utilized receiver operating characteristic curve (ROC) analysis to evaluate parameters that could predict the diagnosis of ECRS., Results: Total 408 CRSwNP patients were enrolled (ECRS group: 163; NECRS group: 245). ECRS group was strongly associated with asthma (6.1% vs. 2.0%, p  = .03), higher blood eosinophil counts (4.3% vs. 2.7%, p  < .01), higher serum IgE (285.3 vs. 50.2 IU/mL, p  = .02), and higher 22-item Sino-Nasal Outcome Test (SNOT-22) score (40.5 vs. 36.7, p  = .03). The ECRS criteria based on ROC curve included the SNOT-22 (>45, 2 points), serum eosinophil count percentage (>4%, 4 points), asthma (4 points), total serum IgE (>140 IU/mL, 4 points), Lund-Mackay score (>9.5, 4 points), and ethmoid-to-maxillary opacification ratio on CT (>1.5, 5 points). The cutoff score was 14 points (sensitivity, 70.2%; specificity, 93.3%)., Conclusions: Clinical-feature-based criteria may predict the diagnosis of ECRS before FESS in Taiwan., Level of Evidence: Level 3., Competing Interests: The authors declare no conflicts of interest relevant to this report., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

The Euphorbiaceae plant Euphorbia neriifolia L. is distributed widely in India, Thailand, Southeastern China, and Taiwan and used as a carminative and expectorant to treat several inflammation-related diseases, such as gonorrhoea, asthma, and cancer. In the course of our search for potential anti-inflammatory agents from the titled plant, 11 triterpenes from the stem of E. neriifolia were isolated and reported in our previous endeavor. Given its rich abundance in triterpenoids, the ethanolic extract in this follow-up exploration has led to the isolation of additional eight triterpenes, including six new euphanes-neritriterpenols H and J-N ( 1 and 3 - 7 )-one new tirucallane, neritriterpenol I ( 2 ), and a known compound, 11-oxo-kansenonol ( 8 ). Their chemical structures were elucidated on the basis of spectroscopic data, including 1D- and 2D NMR, and HRESIMS spectra. The absolute stereochemistry of neritriterpenols was determined by single-crystal X-ray diffraction analysis, ICD spectra, and DP4+ NMR data calculations. Compounds 1 - 8 were also evaluated for their anti-inflammatory activity by using lipopolysaccharide (LPS)-stimulated IL-6 and TNF-α on RAW 264.7 macrophage cells. Intriguingly, the euphane-type triterpenes ( 1 and 3 - 8 ) showed an inhibitory effect on LPS-induced IL-6 but not on TNF-α, while tirucallane-type triterpene 2 showed strong inhibition on both IL-6 and TNF-α., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Huang, Wei, Lo, Lin, Chao, Liao, Shen, Chen, Li, Lin, Tai, Kuo and Liaw.)

Background: Traditional Chinese medicine (TCM) theories assert that body constitution and meridian energy lay the foundation for disease prevention. TCM-based health concepts have not yet been incorporated into mobile health (mHealth) apps for individuals with prediabetes., Objective: The aim of this study was to examine the effectiveness of a TCM mHealth app for individuals with prediabetes., Methods: This randomized controlled trial recruited 121 individuals with prediabetes at a teaching hospital in New Taipei City between February 2020 and May 2021. The participants were randomly assigned to the TCM mHealth app group (n=42), ordinary mHealth app group (n=41), or control group (n=38). All participants received the usual care that included 15-20 minutes of health education about the disease, along with healthy diet and exercise encouragement. The ordinary mHealth app included physical activity (PA), diet, and disease education, along with individual records. The TCM mHealth app additionally included qi and body constitution information, along with constitution-based PA and diet advice. The control group received the usual care alone and did not have access to any app. Data were collected at baseline, at the end of the 12-week intervention, and 1 month after the intervention. Body constitution, including yang-deficiency, yin-deficiency, and phlegm-stasis, was measured according to the Body Constitution Questionnaire, with higher scores indicating a greater deficiency. Body energy was examined using the Meridian Energy Analysis Device. The Short-Form 36 questionnaire was used to evaluate health-related quality of life (HRQOL), which yielded physical component scores and mental component scores, with higher scores indicating better physical and mental aspects of HRQOL, respectively., Results: Compared to the control group, the TCM mHealth app group showed greater improvement in hemoglobin A 1c (HbA 1c ), yang-deficiency and phlegm-stasis body constitution, and BMI; however, no significant differences were found in these outcomes between the TCM mHealth app and ordinary mHealth app groups. The TCM mHealth app group showed better improvement in body energy and mental component scores than the ordinary mHealth app group. There were no significant differences in fasting plasma glucose, yin-deficiency body constitution, Dietary Approaches to Stop Hypertension dietary behavior, and total PA among the three groups after the intervention., Conclusions: Use of either the ordinary or TCM mHealth app improved HRQOL among individuals with prediabetes. Compared to the outcomes of controls not using any app, use of the TCM mHealth app was effective at improving HbA 1c , BMI, yang-deficiency and phlegm-stasis body constitution, and HRQOL. Moreover, using the TCM mHealth app seemed to improve the body energy and HRQOL more than when using the ordinary mHealth app. Further studies with a larger sample size and longer follow-up period may be necessary to determine whether the differences favoring the TCM app are clinically meaningful., Trial Registration: ClinicalTrials.gov NCT04096989; https://clinicaltrials.gov/ct2/show/NCT04096989., (©Hsueh-Wen Chung, Chen-Jei Tai, Polun Chang, Wen-Lin Su, Li-Yin Chien. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 20.06.2023.)

Hepatocellular carcinoma (HCC) remains a difficult-to-treat cancer due to late diagnosis and limited curative treatment options. Developing more effective therapeutic strategies is essential for the management of HCC. Oncolytic virotherapy is a novel treatment modality for cancers, and its combination with small molecules merits further exploration. In this study, we combined oncolytic measles virus (MV) with the natural triterpenoid compound ursolic acid (UA) and evaluated their combination effect against HCC cells, including those harboring hepatitis B virus (HBV) or hepatitis C virus (HCV) replication. We found that the combination of MV and UA synergistically induced more cell death in Huh-7 HCC cells through enhanced apoptosis. In addition, increased oxidative stress and loss of mitochondrial potential were observed in the treated cells, indicating dysregulation of the mitochondria-dependent pathway. Similar synergistic cytotoxic effects were also found in HCC cells harboring HBV or HCV genomes. These findings underscore the potential of oncolytic MV and UA combination for further development as a treatment strategy for HCC.

Background: The effectiveness of hyperbaric oxygen (HBO) therapy for chronic osteomyelitis remains inconclusive. In particular, recent studies have shown that chronic osteomyelitis is a crucial risk factor for cardiovascular diseases. However, the preventive effect of HBO on cardiovascular events has not been reported in patients with chronic osteomyelitis., Methods: We conducted a population-based cohort study to evaluate the impact of HBO on patients with chronic osteomyelitis. Overall, 5312 patients with chronic osteomyelitis were selected from the Taiwan National Health Insurance Database to evaluate the impact of HBO in patients with chronic osteomyelitis. Propensity-score (PS) matching and inverse probability weighting (IPTW) were employed to balance covariates between the HBO and non-HBO groups. The primary outcome was all-cause mortality. The secondary outcomes were myocardial infarction (MI) and stroke hospitalisation. Furthermore, we evaluated the appropriate timing for HBO intervention by the restricted cubic spline (RCS) functions., Results: After 1:4 PS-matching, the HBO group (n = 265) was associated with lower 1-year mortality (hazard ratio [HR], 0.49; 95 % confidence interval [CI], 0.25-0.95) than the non-HBO group (n = 994); this was consistent with the IPTW weighting results (HR, 0.25; 95 % CI, 0.20-0.33). The risk of stroke was lower in the HBO group (HR, 0.46; 95 % CI, 0.34-0.63) than that in the non-HBO group. However, HBO therapy failed to reduce the risk of MI. Using the RCS model, patients with intervals within 90 days (HR, 1.38; 95 % CI, 1.04-1.84) presented a significant risk of 1-year mortality. After 90 days, as the length of interval increased, the risk gradually decreased and became insignificant., Conclusion: The present study revealed that adjunctive HBO could benefit the 1-year mortality and stroke hospitalisation in patients with chronic osteomyelitis. HBO was recommended to be initiated within 90 days of chronic osteomyelitis hospitalisation., Competing Interests: Conflict of interest All authors declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Continuing chemical investigation of the Red Sea sponge Spongia sp. led to the isolation of four new 3,4- seco -3,19-dinorspongian diterpenoid lactones, secodinorspongins A-D ( 1 - 4 ), along with a classical spongian diterpenoid lactone, sponginolide ( 5 ). The chemical structures, including the absolute configurations of these compounds, were elucidated using the extensive spectroscopic study composed of 1D and 2D NMR data analyses, and a comparison between calculated-electronic-circular-dichroism (ECD) and experimental-circular-dichroism (CD) spectra. A plausible biosynthetic pathway of 1 - 4 was also proposed. Furthermore, the cytotoxicity, antibacterial and anti-inflammatory activities of 1 - 5 were evaluated. Compound 1 was found to exhibit inhibitory activity against the growth of Staphylococcus aureus ( S. aureus ), and 4 and 5 exhibited suppression of superoxide-anion generation and elastase release in fMLF/CB-induced human neutrophils.

The present chemical investigation on the organic extract of the soft coral Sarcophyton cinereum has contributed to the isolation of four new cembranoids: 16 β - and 16 α -hydroperoxyisosarcophytoxides ( 1 and 2 ), 16 β - and 16 α -methoxyisosarcophytoxides ( 3 and 4 ), and a known cembranoid, lobocrasol ( 5 ). The structures of all isolates were elucidated by detailed spectroscopic analysis. Their structures were characterized by a 2,5-dihydrofuran moiety, of which the relative configuration was determined by DU8-based calculation for long-range coupling constants ( 4 J H,H ). The cytotoxicity and immunosuppressive activities of all isolates were evaluated in this study.

Background: In Taiwan, Chinese herbal medicine (CHM) is used to treat female infertility. Evidence indicates that the absence of monotherapy efficacy assessment and comparison with mainstream interventions may lead to the improper use of CHM for female infertility., Methods: A retrospective cohort study enrolled female patients at a hospital undergoing CHM intervention to treat infertility from 2012 to 2020 in order to determine the outcomes of CHM monotherapy for female infertility. Kaplan-Meier analysis under strict assumptions was used to estimate the cumulative probability of pregnancy and live births after CHM. Cox hazard regression analysis was used to estimate the hazard ratios of prognostic variables, namely, the woman's age and diagnostic category., Results: 694 women met the inclusion criteria and accounted for 2,145 cycles. A total of 190 pregnancies resulted in 125 live births, all of which were singleton births of babies with 16 perinatal complications requiring hospitalization. The real cumulative pregnancy rate and cumulative live birth rate (CLBR) for the total population after 10 cycles were between 27.4% and 35.2% and between 18% and 22.1%, respectively. Compared with the live birth rate corresponding to patients aged under 35 years, that of older patients, particularly those aged 38-39 years, was significantly lower (hazard ratio: 0.19, 95% confidence interval: 0.11-0.33). Women with other diagnoses, namely, uterine problems or endometriosis, had a greater probability of a live birth than did women with tubal pathology (hazard ratio: 6.31, 95% confidence interval: 1.99-20.07)., Conclusion: To the best of our knowledge, this is the first retrospective study to employ life table analysis to determine the CHM treatment outcomes in terms of female infertility. The study established a basis to compare in vitro fertilization (IVF) with CHM and identified the advantages and disadvantages of CHM for treating female infertility. Although the CLBR of present study is lower than those reported in IVF studies, CHM in treating female infertility can still be beneficial to women aged younger than 38 years or with diagnoses other than tubal pathology and worth recommendation by reproductive specialists according to the promising results gained from the strict criteria. However, in order to determine the optimal timing, possible mechanism, corresponding side effects, and the efficacy of CHM combined with IVF for treating female infertility, rigorous research is required., In Taiwan wird die chinesische Heilpflanzenmedizin (CHM) zur Behandlung weiblicher Infertilität angewendet. Es liegen Hinweise vor, nach denen fehlende Wirksamkeitsbeurteilungen der Monotherapien und Vergleiche mit herkömmlichen Interventionen zu einer unsachgemäßen Anwendung von CHM bei weiblicher Infertilität führen können.Eine retrospektive Kohortenstudie schloss Patientinnen eines Krankenhauses ein, die von 2012 bis 2020 wegen Infertilität mit CHM behandelt wurden, um die Behandlungsergebnisse der CHM-Monotherapie bei weiblicher Infertilität zu ermitteln. Zur Schätzung der kumulativen Wahrscheinlichkeit von Schwangerschaften und Lebendgeburten nach einer CHM-Behandlung wurde die Kaplan-Meier-Analyse unter strengen Annahmen verwendet. Mit Hilfe der Cox-Hazard-Regressionsanalyse wurden die Risikoverhältnisse der prognostischen Variablen Alter der Frau und Diagnosekategorie geschätzt.694 Frauen erfüllten die Einschlusskriterien und die Zahl der Zyklen betrug 2,145. Insgesamt 190 Schwangerschaften führten zu 125 Lebendgeburten, allesamt Einlingsgeburten, mit 16 perinatalen Komplikationen, die eine Hospitalisierung erforderten. Die reale kumulative Schwangerschaftsrate und die kumulative Lebendgeburtenrate (cumulative live birth rate, CLBR) für die Gesamtpopulation nach 10 Zyklen lagen zwischen 27.4% und 35.2% bzw. zwischen 18% und 22.1%. Die Lebendgeburtenrate bei älteren Patientinnen, insbesondere im Alter von 38 bis 39 Jahren, war deutlich niedriger als bei Patientinnen unter 35 Jahren (Hazard Ratio: 0.19, 95%-Konfidenzintervall: 0.11–0.33). Bei Frauen mit anderen Diagnosen wie Gebärmutterproblemen oder Endometriose war die Wahrscheinlichkeit einer Lebendgeburt höher als bei Frauen mit Eileitererkrankungen (Hazard Ratio: 6.31, 95%-Konfidenzintervall: 1.99–20.07).Unseres Wissens ist dies die erste retrospektive Studie, in der die Ergebnisse der CHM-Behandlung bei weiblicher Infertilität mittels Sterbetafelanalyse ermittelt wurden. Die Studie bildet eine Grundlage für den Vergleich von In-vitro-Fertilisation (IVF) mit CHM und zeigt die Vor- und Nachteile der CHM zur Behandlung weiblicher Infertilität auf. Zwar fällt die kumulative Lebendgeburtenrate in der vorliegenden Studie niedriger aus als in IVF-Studien, doch kann die CHM bei der Behandlung weiblicher Infertilität für Frauen unter 38 Jahren oder Frauen, die eine andere Diagnose als eine Eileitererkrankung haben, von Nutzen sein und angesichts der vielversprechenden Ergebnisse, die aus den strengen Kriterien gewonnen wurden, ist sie eine Empfehlung durch Reproduktionsspezialisten wert. Allerdings sind rigorose Forschungsarbeiten erforderlich, um die optimale Zeitplanung, den möglichen Mechanismus, die entsprechenden Nebenwirkungen und die Wirksamkeit der CHM in Kombination mit IVF zur Behandlung der weiblichen Infertilität zu ermitteln., (© 2023 S. Karger AG, Basel.)

Background: The characteristics and surgical outcomes of central compartment atopic disease (CCAD) vary by region and race. Therefore, we aimed to identify the risk factors, symptom severity, and prognosis of CCAD in the Asian population., Methods: This case-control study recruited patients diagnosed with chronic rhinosinusitis with nasal polyps who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. Patients were classified into CCAD and lateral-dominant nasal polyp (LDNP) groups based on endoscopic and computed tomography imaging findings. The demographic data, symptom severity scores, and surgical outcomes of the 2 groups were analyzed., Results: Our study included 442 patients (CCAD group: n = 51; LDNP group: n = 391). We found that CCAD was strongly related to both asthma (9.8% vs 3.5%, p = 0.04) and allergic rhinitis symptoms (43.3% vs 26.6%, p = 0.01). Higher eosinophil counts were detected in blood serum (5.8% vs 2.8%, p < 0.01) and histopathologic profiles (57.0 vs 17.3, p < 0.01) among patients with CCAD. Improvements in 22-item Sino-Nasal Outcome Test (SNOT-22) score and mucociliary clearance time (MCT) after surgical intervention revealed that the CCAD group had a better response to FESS (SNOT-22 score: -31.82 vs -22.66, p < 0.01; MCT: -233.06 vs -191.93 seconds, p = 0.03). The revision FESS rate was not different between the 2 groups., Conclusion: Polyps originating from the central compartment were found to be related to asthma and allergic rhinitis in Taiwanese patients. A higher eosinophil count was suggested in both serum and local nasal tissue from patients with CCAD. FESS serves as an effective treatment for symptom relief in patients with CCAD., (© 2022 ARS-AAOA, LLC.)

Background: Visual impairment (VI) was associated with cognitive impairment. However, different visual trajectories might contribute to different risks of cognitive decline in the elderly., Aims: This study aimed to evaluate the association between visual trajectories and cognitive impairment., Methods: Four thousand two hundred eight community-dwelling elder adults were identified from Waves IV-VII (1999-2011) survey of the Taiwan Longitudinal Study on Aging (TLSA). Cognitive function was determined using the Short Portable Mental Status Questionnaire (SPMSQ) scores. Visual impairment was self-reported and visual trajectories were assessed in at least two waves of the survey. Ordinal logistic regression was performed to estimate adjusted odds ratios (adjORs) and 95% confidence intervals (CIs)., Results: Participants with visual trajectory from no VI to VI had significantly higher risk of cognitive impairment with an adjOR of 1.69 (95% CI 1.12-2.57) than participants without VI. Compared to participants without VI, participants with persistent VI (adjOR 1.32; 95% CI 0.89-1.96) and with visual trajectory from VI to no VI (adjOR 1.25; 95% CI 0.83-1.88) were not associated with cognitive impairment. A protective association between eyeglasses use and cognitive impairment (adjOR 0.69; 95% CI 0.55-0.87) was found in this study. Importantly, cataract was associated with higher risk of cognitive impairment (adjOR 1.34; 95% CI 1.10-1.62). However, nonsurgical cataract treatment did not show protective effect on cognitive impairment in patients with cataract., Conclusions and Discussion: Visual trajectory from no VI to VI is a significant risk factor for cognitive impairment that physicians should pay special attention during community screening., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The main aim of this study is to compare the incidence rate and severity of deep neck infection (DNI) in patients post-UPPP+ T (uvulopalatopharyngoplasty plus tonsillectomy) and without UPPP+ T. We utilized the data derived from the Longitudinal Health Insurance Database (LHID) of the National Health Insurance Research Database (NHIRD) in Taiwan from 1 January 2000 to 31 December 2012. Patients who had undergone combined UPPP and tonsillectomy were selected using National Health Insurance (NHI) surgical order. Patients with DNI were selected using International Classification of Diseases (ICD-9-CM) code. A logistic regression model was applied for risk analysis. There were 1574 patients in the UPPP+ T cohort, and 6,296 patients who did not undergo combined UPPP and tonsillectomy for the control group. Our analysis showed that patients with an obstructive sleep apnea syndrome (OSAS) history constitute 76.1% ( n = 1198) of the UPPP+ T cohort. Compared to the control group, there was no significantly increased incidence rate of DNI after UPPP+ T within 1-60 months. Patients undergoing combined UPPP and tonsillectomy had a lower intubation rate for DNI, with an adjusted odds ratio of 0.47 (95% CI = 0.32-0.69). The combined UPPP and tonsillectomy does not increase the risk of DNI within 1-60 months. Furthermore, combined UPPP and tonsillectomy can reduce the severity for DNI by decreasing the intubation rate and length of hospitalization.

Three new 5,5,6,6,5-pentacyclic spongian diterpenes, spongenolactones A-C ( 1 - 3 ), were isolated from a Red Sea sponge Spongia sp. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and the absolute configurations of 1- 3 were determined on the basis of comparison of the experimental circular dichroism (CD) and calculated electronic circular dichroism (ECD) spectra. Compounds 1 - 3 are the first 5,5,6,6,5-pentacyclic spongian diterpenes bearing an β -hydroxy group at C-1. These metabolites were assayed for their cytotoxic, antibacterial, and anti-inflammatory activities. All three compounds were found to exert inhibitory activity against superoxide anion generation in fMLF/CB-stimulated human neutrophils. Furthermore, 1 showed a higher activity against the growth of Staphylococcus aureus in comparison to 2 .

There is growing evidence of the importance of protease-activated receptor 4 (PAR4), one of thrombin receptors, as a therapeutic target in thrombotic cardiovascular diseases. In the present study, we utilized ligand-based virtual screening, bioassay, and structure-activity relationship study to discover PAR4 antagonists with new chemical scaffolds from natural origin, and examined their application as antiplatelet agents. By using these approaches, we have identified a flavonoid, 7, 4'-dimethoxy-3-hydroxyflavone, that exhibits anti-PAR4 activity. 7, 4'-Dimethoxy-3-hydroxyflavone inhibited PAR4-mediated human platelet aggregation, GPIIb/IIIa activation, and P-selectin secretion. Also, it inhibited PAR4 downstream signaling pathways, including Ca 2+ /protein kinase C, Akt, and MAP kinases ERK and p38, in human platelets, and suppressed PAR4-mediated β-arrestin recruitment in CHO-K1 cells exogenously expressed human PAR4. In a microfluidic system, 7, 4'-dimethoxy-3-hydroxyflavone reduced thrombus formation on collagen-coated chambers at an arterial shear rate in recalcified whole blood. Furthermore, mice treated with 7, 4'-dimethoxy-3-hydroxyflavone were significantly protected from FeCl 3 -induced carotid arterial occlusions, without significantly affecting tail bleeding time. In conclusion, 7, 4'-dimethoxy-3-hydroxyflavone represents a new class of nature-based PAR4 antagonist, it shows effective in vivo antithrombotic properties with less bleeding tendency, and could be a potential candidate for developing new antiplatelet agents., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Real-world evidence refers to patient data derived from the healthcare process. In this study, we used National Health Insurance Research Database (NHIRD) assessments and clinical studies of Ge Gen Tang (GGT, ) in patients with common cold to establish a real-world study model of Traditional Chinese Medicine formulae. GGT is widely prescribed for the treatment of common cold in Taiwan, generally in combination with other medicines. The aim of this study was to determine whether a correlation exists between GGT combined with other medicines and an improvement in cold symptoms. We also established a GGT prescription compatibility system by analyzing Taiwan's NHIRD records for GGT prescription patterns in patients with different types of common cold., Materials and Methods: We extracted and analyzed records from the NHIRD for the period 2000-2015 to determine the most common clinical applications of GGT. GGT and GGT with Chuan Xiung Cha Tiao San were most commonly prescribed for common cold, as per NHIRD recommendations. Records for adults aged 20-65 years who were prescribed GGT for the treatment of common cold (Diagnosis Code ICD-9-460) were included in this study. We assessed the following indicators of the common cold, before and after treatment with GGT: nasal congestion, cough, runny nose, sneezing, sore throat, hoarseness, stiff shoulder, headache, and general physical condition., Results: The cold symptom scores before and after taking the GGT prescriptions significantly differed in the 29 volunteers. The 29 volunteers reported a significantly lower headache severity score after medication than before medication ( p < 0.004). Furthermore, patient scores for general physical condition decreased significantly ( p < 0.01) after medication., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Pei-Ying Chou et al.)

Euphorbia neriifolia L. is widely distributed in India, Thailand, and China and has been used to treat diseases such as rotten sores and asthma as well as for its antidiabetic and anticancer effects. In this study, seven undescribed triterpenes, including six euphanes, neritriterpenols A-B and D-G, and a tirucallane, neritriterpenol C, together with four known triterpenes, were isolated from ethanolic extracts of E. neriifolia stems. Their structures with absolute configurations were determined through detailed spectroscopic data, including 1D and 2D NMR data analyses, single-crystal X-ray diffraction analysis, ECD spectra, and DP4+ NMR data calculations as well as Mo 2 (OAc) 4 -induced ECD analysis. Furthermore, preliminarily evaluation of the anti-inflammatory and anti-proliferative effects of the isolated triterpenes leads to the structure-activity relationship (SAR) studies implying that the unsaturated functional group at the end of the C17 side chain on euphane-type triterpenes may be correlated with the increase of anti-inflammatory and anti-proliferative activities., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Fuzi, Aconiti Lateralis Radix Praeparata, is widely used in Traditional Chinese Medicine (TCM) for the treatment of acute heart failure (HF) for 2000 years. However, the clinical evidence of Fuzi in the treatment of chronic HF is limited, especially when used in combination with Western medications., Materials and Methods: This population-based propensity score (PS)-matched cohort study aimed to evaluate the effectiveness of Fuzi on the chronic HF. From 4753 chronic HF patients who had used TCM herbal medicine, we performed 1:1 PS matching and selected target patients with (n = 921) and without (n = 921) Fuzi use for further analysis. The primary outcomes were all-cause mortality and composite cardiovascular (CV) outcomes. Hazard ratio (HR) was calculated by Cox proportional hazard regression and the competing risk analysis. The dose-response relationship and the association between the initiation of TCM herbal medicine and the primary outcomes were evaluated by restricted cubic spline (RCS) functions., Results: There was no difference in all-cause mortality (HR, 0.99; 95% confidence interval [CI], 0.76-1.27) and composite CV outcomes (HR, 0.96; 95% CI, 0.84-1.11) between the Fuzi user and non-user groups. For CV safety issue, the result showed that Fuzi use was not associated with a higher risk of cardiac arrhythmias (HR, 1.03; 95% CI, 0.83-1.29). The dose-response relationship showed that Fuzi cumulative dose (≥150g) was associated with lower composite CV risk (HR, 0.76; 95% CI, 0.59-0.99). In addition, the RCS model showed that late initiation (≥2.5 years) of TCM herbal drugs in chronic HF patients had a higher risk of all-cause mortality (HR, 1.81; 95%CI, 1.07-3.08)., Conclusions: This study is the first real-world evidence to demonstrate the effect of Fuzi combined with routine HF treatment. Importantly, the result indicated that long-term Fuzi use had a significant benefit in preventing cardiovascular events. The late initiation of TCM herbal drugs was associated with a higher risk of all-cause mortality. Further clinical trials are needed to support or undermine the assumption of using Fuzi and current Western medications to treat chronic HF., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A polyoxygenated and halogenated labdane, spongianol ( 1 ); a polyoxygenated steroid, 3β,5α,9α-trihydroxy-24 S -ethylcholest-7-en-6-one ( 2 ); a rare seven-membered lactone B ring, (22 E ,24 S )-ergosta-7,22-dien-3β,5α-diol-6,5-olide ( 3 ); and an α,β-unsaturated fatty acid, ( Z )-3-methyl-9-oxodec-2-enoic acid ( 4 ) as well as five known compounds, 10-hydroxykahukuene B ( 5 ), pacifenol ( 6 ), dysidamide ( 7 ), 7,7,7-trichloro-3-hydroxy-2,2,6-trimethyl-4-(4,4,4-trichloro-3-methyl-1-oxobu-tylamino)-heptanoic acid methyl ester ( 8 ), and the primary metabolite 2'-deoxynucleoside thymidine ( 9 ), have been isolated from the Red Sea sponge Spongia sp. The stereoisomer of 3 was discovered in Ganoderma resinaceum , and metabolites 5 and 6 , isolated previously from red algae, were characterized unprecedentedly in the sponge. Compounds 7 and 8 have not been found before in the genus Spongia . Compounds 1 - 9 were also assayed for cytotoxicity as well as antibacterial and anti-inflammatory activities.

The role of urate-lowering therapy (ULT) for the primary prevention of cardiovascular (CV) events has been widely discussed, but its evidence for the secondary prevention of myocardial infarction (MI) is limited. Therefore, we conduct a population-based, propensity score-matched cohort study to investigate the CV outcomes among patients with post-MI with and without ULT. A total of 19,042 newly diagnosed in-hospital patients with MI were selected using the Taiwan National Health Insurance Database between January 1, 2005, and December 31, 2016. After 1:1 propensity score matching with covariates, patients with MI with (n = 963) and without (n = 963) ULT were selected for further analysis. The primary outcome was the all-cause mortality and the secondary outcomes were composite CV outcomes, including hospitalization for recurrent MI, stroke, heart failure, and cardiac arrhythmias. ULT users were associated with lower all-cause mortality (adjusted hazard ratio (adjHR), 0.67; 95% confidence interval (CI), 0.51-0.87) compared to the ULT nonusers. In addition, ULT users had a significantly lower risk of recurrent MI, which needed revascularization by percutaneous coronary intervention or coronary artery bypass grafting (adjHR, 0.67; 95% CI, 0.53-0.86) than the ULT nonusers. The primary and secondary outcomes were not different between patients with post-MI who received uricosuric agents and xanthine oxidase inhibitors. The anti-inflammatory effect of ULT plays an essential role in MI management. From a real-world setting, this study shows that ULT is associated with the lower risk of all-cause mortality in patients with post-MI. In addition, the result shows the possible lower incidence of repeat revascularization procedures in the ULT users., (© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Polychlorinated biphenyls (PCBs) have been prohibited for two decades in Japan and Taiwan. The aim of this study was to compare the PCB congeners in maternal and cord serum between two countries. Our study subjects were 248 and 100 mother-child pairs in Japan and Taiwan. The measured levels of 23 serum PCB congeners between two countries were analyzed using gas chromatography-electron capture negative ionization quadrupole mass spectrometry (GC-NICI-qMS). The statistical comparisons were conducted by Student's t-test and principal component analysis with further stratification by maternal age and parity. The maternal total PCBs levels in Japan (426 ± 244 pg/g wet wt) were significantly higher than those in Taiwan (254 ± 155 pg/g wet wt), and the similar results were found in cord total PCBs levels (97 ± 76 and 58 ± 87 pg/g wet wt). It showed different distributions of PCB congeners between two countries. Whether in maternal or cord serum, the CB138, CB153 and CB180 were the highest detectable congeners whether in Japan or Taiwan. And, the CB66, CB99, CB206 and CB209 were only detected in maternal serum of Taiwan. The women of advanced maternal age had higher levels of PCB congeners, especially in Taiwan, and the primiparous women had higher levels of PCB congeners in two countries. In summary, the PCB congeners in Japan's mother-child pairs were with higher levels and different distributions when compared to those in Taiwan, and the maternal age and parity were important factors associated with the PCB levels., 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 © 2021. Published by Elsevier B.V.)

Background: Fibromyalgia is a chronic widespread pain condition that is associated with sleep disturbances and cognitive impairments. Neurofeedback has been demonstrated to improve pain, sleep quality, and fatigue. However, few studies have examined the effect of neurofeedback for patients with fibromyalgia., Aim: To determine the effects of neurofeedback on pain intensity, symptom severity, sleep quality, and cognitive function in patients with fibromyalgia., Design: This study was a randomized controlled trial., Method: Eighty participants were randomized to a neurofeedback group (N = 60), receiving sensorimotor and alpha rhythm feedback for 8 weeks, or a telephone support group (N = 20)., Results: Results from the generalized estimating equation modelling revealed significant group-by-time interactions for Brief Pain Inventory pain severity (B = -1.35, SE = 0.46, p = .003) and pain interference (B = -1.75, SE = 0.41, p < .001), Revised Fibromyalgia Impact Questionnaire total scores (B = -16.41, SE = 3.76, p < .001), sleep onset latency (B = -25.33, SE = 9.02, p = .005), and Psychomotor Vigilance Test error (B = -1.38, SE = 0.55, p = .013) after adjustments for age, sex, duration of illness, and group differences at baseline., Conclusions: An 8-week neurofeedback training regimen of sensorimotor rhythm and alpha brain waves significantly improved pain severity and interference, fibromyalgia symptom severity, sleep latency, and sustained attention in patients with fibromyalgia., (Copyright © 2021 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers., Competing Interests: I.T.L. is currently an employee and shareholder of Moderna, although this work was conducted prior to/independent of his employment. I.T.L. had also received research support unrelated to this study from Genentech (Roche). Moderna did not fund or participate in this study in any form., (© 2021.)

It has been considered that widowed persons have a higher risk of death. This study intended to explore whether social participation could improve this trend. A longitudinal study database was constructed to explore the trend of survival and its change with social participation in widowed persons. The Taiwan Longitudinal Study on Aging (TLSA), based on four consecutive waves of longitudinal follow-up data in 1999, 2003, 2007, and 2011 was linked with the National Death Registry from 1999 through 2012. In total, there were 1417 widowed persons and 4500 nonwidowed persons included in this study, excluding divorced and never-married people. The survival trend analysis was carried out with social participation as the main predictive factor stratified for comparative analysis. Our results showed that the widowed were older than the nonwidowed, were female-dominant, had a lower education level, were more economically stressed, and were less likely to engage in regular exercise, and thus showed generally poorer health; for example, being more vulnerable to having chronic diseases, disability with the Activities of Daily Living (ADL), cognitive impairment with the Short Portable Mental State Questionnaire (SPMSQ), and depression with The Center for Epidemiological Studies-Depression (CES-D). The death risk of the widowed was significantly higher than that of the nonwidowed, but the death trend for those with social participation was significantly lower than that of their counterparts in both the widowed and nonwidowed. After matching with gender and age for widowed persons, the widowed with social participation had a significantly lower risk of death (adjusted hazard ratio (HR), 0.83; 95% confidence interval (CI), 0.71-0.98) compared to the widowed without social participation. It was concluded that social participation can improve the death risk for the widowed, and it is worthily included in health promotion plans and social welfare services for widowed persons.

Background: Coronavirus Disease 2019 (COVID-19) is rapidly transmitted from person to person, causing global pandemic since December 2019. Instantly detecting COVID-19 is crucial for epidemic prevention. In this study, olfactory dysfunction is a significant symptom in mild to moderate COVID-19 patients but relatively rare in other respiratory viral infections. The Taiwan smell identification test (TWSIT) is a speedy and inexpensive option for accurately distinguishing anosmia that also quantifies the degree of anosmia. Using TWSIT in the outpatient clinic for early identifying the patients with mild to moderate COVID-19 can be promising., Methods: Nineteen patients confirmed COVID-19 in central Taiwan were collected and divided into two groups: olfactory dysfunction and non-olfactory dysfunction. Demographic characteristics, laboratory findings, and the results of the olfactory test were compared between these two groups., Findings: Thirteen (68.4%) of the 19 patients had olfactory dysfunction. The patients with olfactory dysfunction were younger than those without this symptom. The statistical difference in age distribution was significant between these two groups (IQR: 25.5-35.5 vs. IQR: 32.5-60.3; p-value: 0.012). There was no significant difference in gender, smoking history, comorbidities, travel history, respiratory tract infection symptoms, and laboratory findings between these two groups., Conclusion: This study demonstrated that young adults were prone to develop olfactory dysfunctions. In the flu season, olfactory dysfunction is considered a specific screening criterion for early detecting COVID-19 in the community. TWSIT can serve as a decent test for quantifying and qualifying olfactory dysfunction., (Copyright © 2021. Published by Elsevier B.V.)

Most patients with Parkinson's disease (PD) gradually develop oropharyngeal dysphagia which is often associated with pneumonia risk. The possible association of benzodiazepine (BZD) and benzodiazepine related drugs (BZRD) use with pneumonia risk has received increasing attention but remains controversial. We investigated pneumonia risk associated with the use of BZDs and BZRDs in older adult patients with PD. This case-control study analyzed data of 551,975 older adult patients with PD between 2001 and 2018 in Taiwan. To minimize potential confounding, we used 1:4 propensity score matching to include older adult patients without pneumonia as controls. Incident pneumonia risk was significantly higher in current (adjusted odds ratio (aOR) = 1.25, 95% CI = 1.23-1.27) and past (aOR = 1.13, 95% CI = 1.11-1.15) users of BZDs. Regarding BZRDs, recent (aOR = 1.08, 95% CI = 1.06-1.11) and past (aOR = 0.89, 95% CI = 0.88-0.91) users had higher and lower risks of incident pneumonia, respectively. Pneumonia risk varied based on their use of BZDs and BZRDs. In these individuals, incident pneumonia risk was high in users of BZDs, such as midazolam, lorazepam, flunitrazepam, estazolam, and clonazepam. Regarding the use of BZRDs, zopiclone increased incident pneumonia risk.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Gut microbiota are highly associated with CRC, and Fusobacterium nucleatum was found to be enriched in CRC lesions and correlated with CRC carcinogenesis and metastases. Paris polyphylla is a well-known herbal medicine that showed anticancer activity. The present study demonstrates that P. polyphylla inhibited the growth of CRC cells. In addition, treating with active compounds pennogenin 3- O -beta-chacotrioside and polyphyllin VI isolated from P. polyphylla inhibited the growth of F. nucleatum . We also found that extracellular vesicles (EVs) released from F. nucleatum could promote mitochondrial fusion and cell invasion in CRC cells, whereas active components from P. polyphylla could dampen such an impact. The data suggest that P. polyphylla and its active ingredients could be further explored as potential candidates for developing complementary chemotherapy for the treatment of CRC.

Background: As time evolved, traditional Chinese medicine (TCM) became integrated into the global medical system as complementary treatments. Some essential TCM herbs started to play a limited role in clinical practices because of Western medication development. For example, Fuzi (Aconiti Lateralis Radix Praeparata) is a toxic but indispensable TCM herb. Fuzi was mainly used in poor circulation and life-threatening conditions by history records. However, with various Western medication options for treating critical conditions currently, how is Fuzi used clinically and its indications in modern TCM are unclear. This study aimed to evaluate Fuzi and Fuzi-based formulas in modern clinical practices using artificial intelligence and data mining methods. Methods: This nationwide descriptive study with market basket analysis used a cohort selected from the Taiwan National Health Insurance database that contained one million national representatives between 2003 and 2010 used for our analysis. Descriptive statistics were performed to demonstrate the modern clinical indications of Fuzi. Market basket analysis was calculated by the Apriori algorithm to discover the association rules between Fuzi and other TCM herbs. Results: A total of 104,281 patients using 405,837 prescriptions of Fuzi and Fuzi-based formulas were identified. TCM doctors were found to use Fuzi in pulmonary (21.5%), gastrointestinal (17.3%), and rheumatologic (11.0%) diseases, but not commonly in cardiovascular diseases (7.4%). Long-term users of Fuzi and Fuzi-based formulas often had the following comorbidities diagnosed by Western doctors: osteoarthritis (31.0%), peptic ulcers (29.5%), hypertension (19.9%), and COPD (19.7%). Patients also used concurrent medications such as H2-receptor antagonists, nonsteroidal anti-inflammatory drugs, β-blockers, calcium channel blockers, and aspirin. Through market basket analysis, for the first time, we noticed many practical Fuzi-related herbal pairs such as Fuzi-Hsihsin (Asari Radix et Rhizoma)-Dahuang (Rhei Radix et Rhizoma) for neurologic diseases and headache. Conclusion: For the first time, big data analysis was applied to uncover the modern clinical indications of Fuzi in addition to traditional use. We provided necessary evidence on the scientific use of Fuzi in current TCM practices, and the Fuzi-related herbal pairs discovered in this study are helpful to the development of new botanical drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tai, El-Shazly, Tsai, Csupor, Hohmann, Wu, Tseng, Chang and Wang.)

Background: Previous studies neglected death as a critical competing risk while estimating the cancer risk for digoxin users. Therefore, the current study aims to assess the effectiveness of digoxin on cancer prevention by competing risk analysis. Methods: We performed a population-based retrospective cohort study using the Taiwan National Health Insurance Research database between 1998 and 2010. After one-to-one propensity score-matching from 36,160 patients with defined criteria, we enrolled 758 patients both in digoxin and β-blocker group for further analysis. Results: The results showed that the digoxin group had higher all-cause mortality than the β-blocker group in the 4- year (10.4 vs. 4.9%) and 8 years (13.6 vs. 7.0%) follow-up. The subdistribution HR of cancer incidence in the digoxin group compared to the β-blocker group was 1.99 (95% confidence interval [CI]: 1.22-3.01) and 1.46 (95% CI: 1.01-2.15) in the 4 years and 8 years follow-up, respectively. Conclusions: The result of our study showed the usage of digoxin has no benefit in cancer prevention compared with β-blocker. The possibility of β-blocker as a new drug candidate for cancer prevention needs further clinical evaluation. The current study also emphasized the necessity of competing risk analysis applying to similar clinical researches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tai, Yang, Tseng, Chang and Wang.)

Background/purpose: Juglone, a natural compound widely found in Juglandaceae plants, has been suggested as a potential drug candidate for treating cancer, inflammation, and diabetic vascular complications. In the present study, the antiplatelet effect and underlying mechanisms of juglone were investigated for the first time., Study Design/methods: Human platelet aggregation and activation were measured by turbidimetric aggregometry, flow cytometry, and Western blotting. In vitro antithrombotic activity of juglone was assessed using collagen-coated flow chambers under whole-blood flow conditions. The effect of juglone on protein disulfide isomerase (PDI) activity was determined by the dieosin glutathione disulfide assay., Results: Juglone (1 - 5 μM) inhibited platelet aggregation and glycoprotein (GP) IIb/IIIa activation caused by various agonists. In a whole blood flow chamber system, juglone reduced thrombus formation on collagen-coated surfaces under arterial shear rates. Juglone abolished intracellular Ca 2+ elevation and protein kinase C activation caused by collagen, but had no significant effect on that induced by G protein-coupled receptor agonists. In contrast, Akt activation caused by various agonists were inhibited in juglone-treated platelets. Additionally, juglone showed inhibitory effects on both recombinant human PDI and platelet surface PDI at concentrations similar to those needed to prevent platelet aggregation., Conclusion: Juglone exhibits potent in vitro antiplatelet and antithrombotic effects that are associated with inhibition of Akt activation and platelet surface PDI activity., (Copyright © 2020. Published by Elsevier GmbH.)

Background: Cases of breastfeeding- and breast-milk-related jaundice tend to increase with increased rates of breastfeeding. Diagnoses of jaundice often lead mothers to discontinue breastfeeding because of assumptions that breastfeeding may exacerbate neonatal jaundice and lengthen the duration of phototherapy treatment., Purpose: This study was designed to explore the effect of neonatal jaundice on breastfeeding duration and exclusivity during the first 4 months postpartum., Methods: This study applied a two-group comparative and follow-up design. The two groups comprised 135 and 160 mothers of infants, respectively, with and without neonatal jaundice. All of the participants were recruited from three certified baby-friendly hospitals in northern Taiwan. Follow-up was conducted by telephone at 1 and 4 months postpartum., Results: Mean breastfeeding duration was longer in the group of participants whose infants had neonatal jaundice (group with neonatal jaundice) than in the group whose infants did not have this condition (group without neonatal jaundice; 102.00 vs. 89.85 days, p = .007). The degree of breastfeeding was higher in the group with neonatal jaundice, although the difference was significant only at 1 month postpartum and not during hospitalization or at 4 months postpartum. The results of a Cox regression model showed that the group without neonatal jaundice was more likely to discontinue breastfeeding (adjusted hazard ratio = 1.68, 95% CI [1.08, 2.62]). A generalized estimating equation model suggests that infants with neonatal jaundice had a higher likelihood of being breastfed for at least half of their feedings (adjusted OR = 1.53, 95% CI [1.04, 2.25])., Conclusions: On the basis of the results of this study, neonatal jaundice is not an obstacle to breastfeeding in pro-breastfeeding hospital environments. Participants whose infants developed neonatal jaundice were found in this study to breastfeed more often, which promotes breastfeeding success., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Previous studies have reported associations between hearing impairment (HI) and cognitive impairment, but the evidence is not conclusive while considering concurrent geriatric syndromes. Especially, evidence from previous studies rarely came from Asian studies. This study aimed to evaluate the independent effects of HI and hearing aid use on the incidence of cognitive impairment while considering most geriatric confounders., Methods: This population-based, propensity-score matched cohort study used cohort from Waves IV-VII (1999-2011) survey of the Taiwan Longitudinal Study on Aging (TLSA). Cognitive impairment was identified based on Short Portable Mental Status Questionnaire (SPMSQ) scores. The hazard ratio (HR) was calculated using the Cox proportional hazard regression adjusting for age, sex, comorbidities, socioeconomic status, Center for Epidemiologic Studies Depression (CES-D) scores, the instrumental activities of daily living scale, mobility condition and quality of life. In addition, social support and participation were also considered as confounders in the analysis. To assess the robustness of our findings, we conducted a sensitivity analysis designed to access unmeasured confounding factors by calculating E-values., Results: After 1:1 propensity-score matching, we included 709 participants in both the HI and non-HI groups with a mean age of 73.4 years and 39.4% of participants were female. The mean follow-up was 8.9 ± 3.9 years. The HI group had a higher incidence of cognitive impairment than the non-HI group (74.5% vs. 69.1%, respectively), with an adjusted HR of 1.16 (95% confidence interval [CI], 1.03-1.32) based on a 12-year follow up. The E-value was 1.45 for the estimate, which provided evidence for this study's robustness. Although, a subgroup analysis showed that hearing aid use was associated with lower incidences of cognitive impairment (66.3% vs. 75.6%) when compared to non-users in the HI group, the adjusted HR of 0.82 (95% CI, 0.61-1.09) revealed no significant differences., Conclusions: HI was an independent risk factor of incident cognitive impairment on top of concurrent geriatric syndromes. Early HI detection may thus be effective for preventing cognitive decline. Further studies are needed to evaluate the effect of hearing aid use on the prevention of cognitive decline.

Chemical investigation of a Red Sea Spongia sp. led to the isolation of four new compounds, i.e., 17-dehydroxysponalactone ( 1 ), a carboxylic acid, spongiafuranic acid A ( 2 ), one hydroxamic acid, spongiafuranohydroxamic acid A ( 3 ), and a furanyl trinorsesterpenoid 16- epi -irciformonin G ( 4 ), along with three known metabolites (-)-sponalisolide B ( 5 ), 18-nor- 3,17-dihydroxy-spongia-3,13(16),14-trien-2-one ( 6 ), and cholesta-7-ene-3β,5α-diol-6-one ( 7 ). The biosynthetic pathway for the molecular skeleton of 1 and related compounds was postulated for the first time. Anti-inflammatory activity of these metabolites to inhibit superoxide anion generation and elastase release in N -formyl-methionyl-leucyl phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophil cells and cytotoxicity of these compounds toward three cancer cell lines and one human dermal fibroblast cell line were assayed. Compound 1 was found to significantly reduce the superoxide anion generation and elastase release at a concentration of 10 μM, and compound 5 was also found to display strong inhibitory activity against superoxide anion generation at the same concentration. Due to the noncytotoxic activity and the potent inhibitory effect toward the superoxide anion generation and elastase release, 1 and 5 can be considered to be promising anti-inflammatory agents.

Oncolytic viruses (OVs) and phytochemical ursolic acid (UA) are two efficacious therapeutic candidates in development against breast cancer, the deadliest women's cancer worldwide. However, as single agents, OVs and UA have limited clinical efficacies. As a common strategy of enhancing monotherapeutic anticancer efficacy, we explored the combinatorial chemovirotherapeutic approach of combining oncolytic measles virus (MV), which targets the breast tumor marker Nectin-4, and the anticancer UA against breast adenocarcinoma. Our findings revealed that in vitro co-treatment with UA synergistically potentiated the killing of human breast cancer cells by oncolytic MV, without UA interfering the various steps of the viral infection. Mechanistic studies revealed that the synergistic outcome from the combined treatment was mediated through UA's potentiation of apoptotic killing by MV. To circumvent UA's poor solubility and bioavailability and strengthen its clinical applicability, we further developed UA nanoparticles (UA-NP) by nanoemulsification. Compared to the non-formulated UA, UA-NP exhibited improved drug dissolution property and similarly synergized with oncolytic MV in inducing apoptotic breast cancer cell death. This oncolytic potentiation was partly attributed to the enhanced autophagic flux induced by the UA-NP and MV combined treatment. Finally, the synergistic effect from the UA-NP and MV combination was also observed in BT-474 and MDA-MB-468 breast cancer cells. Our study thus highlights the potential value of oncolytic MV and UA-based chemovirotherapy for further development as a treatment strategy against breast cancer, and the feasibility of employing nanoformulation to enhance UA's applicability.

Objectives: The study aimed to develop a brief geriatric assessment (BGA) tool for the general practitioner to evaluate geriatric syndromes in community-dwelling older adults., Design: A cross-sectional study., Setting: 58 communities from four aging cities in Taiwan., Participants: 1,258 community-dwelling older adults aged 65 years and above., Measurements: The BGA targeted physical function impairment, cognitive impairment, and mood impairment. The cutoff values of physical function tests (handgrip strength and 6-meter walk test [6MWT]) were estimated by receiver operating characteristic analysis. Second, the diagnostic validity of the BGA was calculated in terms of sensitivity, specificity, and predictive values, which were compared to corresponding comprehensive geriatric assessment (CGA) items. Third, the associated risk factors of geriatric syndromes were selected using stepwise logistic regression. Finally, we combined items selected from literature and CGA and then proposed a practical BGA framework., Results: The proposed BGA comprised dominant handgrip strength, 6MWT, self-report personal birthday, address, and telephone number, question 'Do you have depressive mood for the past two weeks?', Rinne tuning-fork tests, Snellen scale, and body mass index. It evaluated multidimensional aspects of geriatrics syndromes including physical, cognitive, mood, and sensory impairment, sarcopenia, and nutrition status. Sensitivities in the Taiwan BGA items ranged from 48% for dominant handgrip strength to 97.6% for 6MWT corresponding to physical impairment; 58.3% for cognitive impairment corresponding to Short Portable Mental Status Questionnaire; 62.7% for mood impairment corresponding to Geriatric Depression Scale. The Taiwan BGA for the general practitioner takes less than 10 minutes and is suitable in the community setting., Conclusion: Early management of geriatric syndromes in the community is important. The current study demonstrated a practical BGA tool for the general practitioner to comprehensively assess geriatric syndromes in community-dwelling older adults., Competing Interests: All authors declare that they have no competing interests.

Evidence shows that chronic rhinosinusitis (CRS) is associated with prior presence of autoimmune diseases; however, large-scale population-based studies in the literature are limited. We conducted a population-based case-control study investigating the association between CRS and premorbid autoimmune diseases by using the National Health Insurance Research Database in Taiwan. The CRS group included adult patients newly diagnosed with CRS between 2001 and 2013. The date of diagnosis was defined as the index date. The comparison group included individuals without CRS, with 1:4 frequency matching for gender, age, and index year. Premorbid diseases were forward traced to 1996. Univariate and multivariate logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals. The CRS group consisted of 30,611 patients, and the comparison group consisted of 122,444 individuals. Patients with CRS had a higher significant association with premorbid autoimmune diseases (adjusted OR 1.39 [1.28-1.50]). Specifically, patients with CRS had a higher significant association with ankylosing spondylitis, polymyositis, psoriasis, rheumatoid arthritis, sicca syndrome, and systemic lupus erythematosus (adjusted OR 1.49 [1.34-1.67], 3.47 [1.12-10.8], 1.22 [1.04-1.43], 1.60 [1.31-1.96], 2.10 [1.63-2.72], and 1.69 [1.26-2.25]). In subgroup analysis, CRS with and without nasal polyps demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 1.34 [1.14-1.58] and 1.50 [1.38-1.62]). In addition, CRS with fungal and non-fungal infections also demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 2.02 [1.72-2.49] and 1.39 [1.28-1.51]). In conclusion, a significant association between CRS and premorbid autoimmune diseases has been identified. These underlying mechanisms need further investigation.