Decreased Risk of Stroke in People Using Red Yeast Rice Prescriptions (LipoCol Forte®): a Total Population-Based Retrospective Cohort Study.

The influence of red yeast rice (RYR) on the risk of incident stroke remains underexplored. We aimed to compare the risk of stroke between people with and without use of RYR prescriptions. We used research data from the National Health Insurance Program in Taiwan and identified 34,723 adults (aged ≥20 years) who first received the RYR prescription from 2010 to 2014. To select the appropriate control group, we used frequency matching by age and sex (case-control ratio = 1 : 1) and identified a non-RYR cohort that included 34,723 adults who first received lovastatin. Events of an incident stroke that occurred during the follow-up period of 2010-2017 were identified from medical claims. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of stroke risk associated with RYR prescription were calculated in the multiple Cox proportional hazard model. Compared with the non-RYR cohort, patients who received RYR prescriptions had a decreased risk of stroke (HR 0.65, 95% CI 0.59-0.71), including hemorrhagic stroke (HR 0.60, 95% CI 0.44-0.83), ischemic stroke (HR 0.49, 95% CI 0.43-0.57), and other types of strokes (HR 0.53, 95% CI 0.42-0.67). The association between RYR prescription and stroke risk was significant in both sexes and in people aged more than 40 years, as well as in those individuals with various medical conditions. The frequency of RYR prescription (HR 0.57, 95% CI 0.50-0.64) was associated with a decreased risk of stroke with a dose-response relationship (p for trend<0.0001). This study showed a potentially positive effect of RYR on the risk of stroke. However, compliance with medication use should be cautioned. The findings of this study require future studies to validate the beneficial effects of RYR prescription on stroke risk.

Genistein Triggers Translocation of Estrogen Receptor-Alpha in Mitochondria to Induce Expressions of ATP Synthesis-Associated Genes and Improves Energy Production and Osteoblast Maturation.

Our previous study showed that estrogen can induce mitochondrial adenosine triphosphate (ATP) synthesis-associated gene expressions and osteoblast maturation. Genistein, a phytoestrogenic isoflavone that is widely found in various foods and traditional herb products, is beneficial for osteogenesis by selectively triggering estrogen receptor alpha (ER[Formula: see text] expression. In this study, we further investigated the mechanisms of genistein-induced energy production and osteoblast activation. Exposure of rat calvarial osteoblasts and human U-2 OS cells to genistein triggered osteoblast activation without affecting cell survival. Treatment with genistein time-dependently induced ER[Formula: see text] mRNA and protein expressions in rat calvarial osteoblasts. Analyses by confocal microscopy and immunoblotting showed that genistein stimulated translocation of ER[Formula: see text] from the cytoplasm to mitochondria. Subsequently, expressions of mitochondrial cytochrome c oxidase (COX) I and II mRNAs and proteins in primary rat osteoblasts were induced after exposure to genistein. Knocking-down ER[Formula: see text] concurrently inhibited genistein-induced COX I and II mRNA expressions. In addition, mitochondrial complex enzyme activities, the mitochondrial membrane potential, and cellular ATP levels in rat calvarial osteoblasts were time-dependently augmented by genistein. Suppressing ER[Formula: see text] expression instantaneously lowered genistein-induced enhancements of mitochondrial energy production and osteoblast activation. Effects of genistein on ER[Formula: see text] translocation, COX I and II mRNA expressions, ATP synthesis, and osteoblast activation were further confirmed in human U-2 OS cells. This study showed that genistein can stimulate energy production and consequent osteoblast activation via inducing ER[Formula: see text]-mediated mitochondrial ATP synthesis-linked gene expressions.

Risk of diabetes in stroke patients who used Bu Yang Huan Wu Tang: A nationwide propensity-score matched study.

BACKGROUND: The utilization of traditional Chinese medicine is a common therapeutic approach for stroke patients in Chinese population, but little is known about the effect of Bu Yang Huan Wu Tang (BYHWT) on post-stroke diabetes. PURPOSE: We aimed to evaluate the risk of diabetes in stroke patients who used BYHWT. STUDY DESIGN: A retrospective cohort study based on a real-world database was conducted. METHODS: Newly diagnosed stroke patients receiving inpatient care from 2000 to 2004 were identified using a large-scale insurance database in Taiwan. Propensity score matching was used to select eligible stroke patients who did (n = 9849) and did not (n = 9849) receive BYHWT. These two groups were followed up until the end of 2009 to track incident diabetes. Cox proportional hazard models were used to calculate the adjusted hazard rations (HRs) and 95% confidence intervals (CIs) for post-stroke diabetes associated with BYHWT during the follow-up period. RESULTS: Stroke patients who used BYHWT had a reduced incidence of diabetes (14.1% vs. 19.0%, p < 0.0001) and reduced risk of diabetes (HR 0.77; 95% CI 0.72 to 0.83) compared with the control group. The association between BYHWT and reduced risk of post-stroke diabetes was significant across sexe, age group, and stroke subtype. Additionally, the use of BYHWT was associated with a reduced risk of post-stroke diabetes even after excluding the initial three months of diabetes cases in the sensitivity analysis. CONCLUSIONS: Stroke patients who received BYHWT therapy had a reduced risk of diabetes, and a positive effect was observed in various subgroups. However, future clinical trials will be necessary to validate the present findings and identify the biochemical mechanism involved.

Adverse outcomes after major surgery in children with intellectual disability.

AIM: To evaluate outcomes after major surgery in children and adolescents with intellectual disability. METHOD: We used 2004 to 2013 claims data from Taiwan's National Health Insurance programme to conduct a nested cohort study, which included 220 292 surgical patients aged 6 to 17 years. A propensity score matching procedure was used to select 2173 children with intellectual disability and 21 730 children without intellectual disability for comparison. Logistic regression was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the postoperative complications and 30-day mortality associated with intellectual disability. RESULTS: Children with intellectual disability had a higher risk of postoperative pneumonia (OR 2.16, 95% CI 1.48-3.15; p<0.001), sepsis (OR 1.67, 95% CI 1.28-2.18; p<0.001), and 30-day mortality (OR 2.04, 95% CI 1.05-3.93; p=0.013) compared with children without intellectual disability. Children with intellectual disability also had longer lengths of hospital stay (p<0.001) and higher medical expenditure (p<0.001) when compared with children with no intellectual disability. INTERPRETATION: Children with intellectual disability experienced more complications and higher 30-day mortality after surgery when compared with children without intellectual disability. There is an urgent need to revise the protocols for the perioperative care of this specific population. WHAT THIS PAPER ADDS: Surgical patients with intellectual disability are at increased risk of postoperative pneumonia, sepsis, and 30-day mortality. Intellectual disability is associated with higher medical expenditure and increased length of stay in hospital after surgical procedures. The influence of intellectual disability on postoperative outcomes is consistent in both sexes and those aged 10 to 17 years. Low income and a history of fractures significantly impacts postoperative adverse events for patients with intellectual disability.

Genistein Improves Bone Healing via Triggering Estrogen Receptor Alpha-Mediated Expressions of Osteogenesis-Associated Genes and Consequent Maturation of Osteoblasts.

Osteoporosis-associated fractures may cause higher morbidity and mortality. Our previous study showed the effects of genistein, a phytoestrogen, on the induction of estrogen receptor alpha (ERα) gene expression and stimulation of osteoblast mineralization. In this study, rat calvarial osteoblasts and an animal bone defect model were used to investigate the effects of genistein on bone healing. Treatment with genistein caused a time-dependent increase in alkaline phosphatase (ALP) activity in rat osteoblasts. Levels of cytosolic and nuclear ERα significantly augmented following exposure to genistein. Subsequently, genistein elevated levels of ALP mRNA and protein in rat osteoblasts. Moreover, genistein induced other osteogenesis-associated osteocalcin and Runx2 mRNA and protein expressions. Knocking-down ERα using RNA interference concurrently inhibited genistein-induced Runx2, osteocalcin, and ALP mRNA expression. Attractively, administration of ICR mice suffering bone defects with genistein caused significant increases in the callus width, chondrocyte proliferation, and ALP synthesis. Results of microcomputed tomography revealed that administration of genistein increased trabecular bone numbers and improved the bone thickness and volume. This study showed that genistein can improve bone healing via triggering ERα-mediated osteogenesis-associated gene expressions and subsequent osteoblast maturation.

Decreased risk of pneumonia in stroke patients receiving acupuncture: A nationwide matched-pair retrospective cohort study.

BACKGROUND: Acupuncture treatment is common among stroke patients, but there is limited information available on whether acupuncture effectively prevents post-stroke pneumonia. The aim of this study was to analyze the differential risk of pneumonia after stroke between patients who did and did not receive acupuncture after discharge. METHODS: We used the Taiwan National Health Insurance Research Database to conduct a retrospective cohort study using propensity score matched-pairs of new stroke patients in 2000-2004 who did and did not receive acupuncture post-stroke. Both cohorts were followed up until the end of 2009 for new-onset pneumonia. After correcting for immortal time bias, the incidence and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of pneumonia associated with acupuncture use were calculated using multivariate Cox proportional hazard models. RESULTS: Overall, 12557 stroke patients with 12557 paired controls were included in the analysis; pneumonia was diagnosed in 6796 (27.1%). Stroke patients receiving acupuncture had a lower incidence of pneumonia than those without acupuncture (53.4 vs. 58.9 per 1000 person-years), with an adjusted HR of 0.86 (95% CI 0.82-0.90). The association between pneumonia risk and acupuncture use was significant in men (HR 0.92, 95% CI 0.86-0.98) and women (HR 0.79, 95% 0.70-0.82) and was also observed in every age group from 20-79 years. CONCLUSION: Stroke patients receiving acupuncture had a lower risk of pneumonia than those who did not. Further randomized control studies are needed to validate the protective effect of acupuncture on the risk of pneumonia among stroke patients.

Outcomes after stroke in patients receiving adjuvant therapy with traditional Chinese medicine: A nationwide matched interventional cohort study.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of traditional Chinese medicine (TCM) was high in stroke patients but limited information was available on whether TCM is effective on post-stroke outcomes. The aim of this study is to compare the outcomes of stroke patients with and without receiving adjuvant TCM therapy. MATERIALS AND METHODS: Using Taiwan's National Health Insurance Research Database, we conducted a nationwide cohort study and selected hospitalized stroke patients receiving routine care with (n=1734) and without (n=1734) in-hospital adjuvant TCM therapy by propensity score matching procedures. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of poststroke complications and mortality associated with in-hospital adjuvant TCM therapy were calculated. The use of medical resource was also compared between stroke patients with and without adjuvant TCM therapy. RESULTS: Compared with hospitalized stroke patients receiving routine care alone, hospitalized stroke patients receiving routine care and adjuvant TCM therapy exhibited decreased risks of urinary tract infection (HR 0.82, 95% CI 0.68-1.00), pneumonia (HR 0.60, 95% CI 0.47-0.76), epilepsy (HR 0.67, 95% CI 0.49-0.96), gastrointestinal hemorrhage (HR 0.68, 95% CI 0.47-0.98), and mortality (HR 0.37, 95% CI 0.19-0.70) within 3 months after stroke admission. The corresponding 6-month HRs for urinary tract infection, pneumonia, gastrointestinal hemorrhage, and mortality were 0.83, 0.63, 0.64, and 0.40, respectively. Less use and expenditure of hospitalization were found in those received adjuvant TCM therapy. CONCLUSIONS: Hospitalized stroke patients who received routine care and adjuvant TCM therapy exhibited reduced adverse outcomes after admission within a 6-month follow-up period.

Adjunctive traditional Chinese medicine therapy improves survival in patients with advanced breast cancer: a population-based study.

BACKGROUND: Traditional Chinese medicine (TCM) is one of the most common complementary and alternative medicines used in the treatment of patients with breast cancer. However, the clinical effect of TCM on survival, which is a major concern in these individuals, lacks evidence from large-scale clinical studies. METHODS: The authors used the Taiwan National Health Insurance Research Database to conduct a retrospective population-based cohort study of patients with advanced breast cancer between 2001 and 2010. The patients were separated into TCM users and nonusers, and Cox regression models were applied to determine the association between the use of TCM and patient survival. RESULTS: A total of 729 patients with advanced breast cancer receiving taxanes were included in the current study. Of this cohort, the mean age was 52.0 years; 115 patients were TCM users (15.8%) and 614 patients were TCM nonusers. The mean follow-up was 2.8 years, with 277 deaths reported to occur during the 10-year period. Multivariate analysis demonstrated that, compared with nonusers, the use of TCM was associated with a significantly decreased risk of all-cause mortality (adjusted hazards ratio [HR], 0.55 [95% confidence interval, 0.33-0.90] for TCM use of 30-180 days; adjusted HR, 0.46 [95% confidence interval, 0.27-0.78] for TCM use of >180 days). Among the frequently used TCMs, those found to be most effective (lowest HRs) in reducing mortality were Bai Hua She She Cao, Ban Zhi Lian, and Huang Qi. CONCLUSIONS: The results of the current observational study suggest that adjunctive TCM therapy may lower the risk of death in patients with advanced breast cancer. Future randomized controlled trials are required to validate these findings.

Biphasic effect of curcumin on morphine tolerance: a preliminary evidence from cytokine/chemokine protein array analysis.

The aim of this study was to evaluate the effect of curcumin on morphine tolerance and the corresponding cytokine/chemokine changes. Male ICR mice were made tolerant to morphine by daily subcutaneous injection for 7 days. Intraperitoneal injections of vehicle, low-dose or high-dose curcumin were administered 15 min after morphine injection, either acutely or chronically for 7 days to test the effect of curcumin on morphine-induced antinociception and development of morphine tolerance. On day 8, cumulative dose-response curves were generated and the 50% of maximal analgesic dose values were calculated and compared among groups. Corresponding set of mice were used for analyzing the cytokine responses by antibody-based cytokine protein array. Acute, high-dose curcumin enhanced morphine-induced antinociception. While morphine tolerance was attenuated by administration of low-dose curcumin following morphine injections for 7 days, it was aggravated by chronic high-dose curcumin following morphine injection, suggesting a biphasic effect of curcumin on morphine-induced tolerance. Of the 96 cytokine/chemokines analyzed by mouse cytokine protein array, 14 cytokines exhibited significant changes after the different 7-day treatments. Mechanisms for the modulatory effects of low-dose and high-dose curcumin on morphine tolerance were discussed. Even though curcumin itself is a neuroprotectant and low doses of the compound serve to attenuate morphine tolerance, high-doses of curcumin might cause neurotoxicity and aggravate morphine tolerance by inhibiting the expression of antiapoptotic cytokines and neuroprotective factors. Our results indicate that the effect of curcumin on morphine tolerance may be biphasic, and therefore curcumin should be used cautiously.

Ginkgo biloba extract suppresses endotoxin-mediated monocyte activation by inhibiting nitric oxide- and tristetraprolin-mediated toll-like receptor 4 expression.

Monocytes expressing toll-like receptor 4 (TLR4) play a major role in regulating the innate immune response and are involved in systemic inflammation. Previous studies have shown that Ginkgo biloba extract (GBE) may act as a therapeutic agent for some cardiovascular and neurological disorders. The objective of this study was to determine whether GBE could modulate immunity in human cells. The monocytic cell line THP-1 was used. Enzyme-linked immunosorbent assay results showed that lipopolysaccharide (LPS) induces the expression of monocyte chemotactic protein-1 (MIP-1), tumor necrosis factor-α, stromal cell-derived factor-1, and MIP-1α, and this induction may be repressed by GBE treatment due to TLR4 blockade. The Griess reagent assay and western blot analysis showed that GBE-mediated inhibition of TLR4 expression was associated with the activation of mitogen-activated protein kinase and production of nitric oxide (NO). Actinomycin D chase experiments demonstrated that GBE decreased the TLR4 mRNA stability in cells. Confocal microscopy and real-time polymerase chain reaction showed that GBE induced the expression of intracellular tristetraprolin (TTP). Transfection with TTP siRNA reversed the effects of GBE in naïve or TLR4-overexpressing cells. Treatment with SNAP (an NO donor) may increase intracellular TTP expression in cells. Immunoprecipitation analysis showed that GBE mediates TTP activation and increases the interaction of TTP with the 3' untranslated region (UTR) of TLR4 mRNA by regulating NO production. Our findings indicate that GBE could decrease the sensitivity of monocytes to LPS. Utilizing TTP to control TLR4 expression may be a promising approach for controlling systemic inflammation, and GBE may have potential applications in the clinical treatment of immune diseases.

Interaction effects of ultrafine carbon black with iron and nickel on heart rate variability in spontaneously hypertensive rats.

BACKGROUND: Particulate matter (PM) has been reported to be associated with alterations in heart rate variability (HRV); however, the results are inconsistent. We propose that different components of PM cause the discrepancy. OBJECTIVE: In this study, our goal was to determine whether different types of exposure would cause different HRV effects, and to verify the interactions between co-exposing components. METHODS: Ultrafine carbon black (ufCB; 14 nm; 415 microg and 830 microg), ferric sulfate [Fe(2)(SO(4))(3); 105 microg and 210 microg], nickel sulfate (NiSO(4); 263 mug and 526 microg), and a combination of high-dose ufCB and low-dose Fe(2)(SO(4))(3) or NiSO(4) were intratracheally instilled into spontaneously hypertensive rats. Radiotelemetry data were collected in rats for 72 hr at baseline and for 72 hr the following week to determine the response to exposure. Effects of exposure on 5-min average of normal-to-normal intervals (ANN), natural logarithm-transformed standard deviation of the normal-to-normal intervals (LnSDNN), and root mean square of successive differences of adjacent normal-to-normal intervals (LnRMSSD) were analyzed using self-control experimental designs. RESULTS: Both high- and low-dose ufCB decreased ANN marginally around hour 30, with concurrent increases of LnSDNN. LnRMSSD returned to baseline levels after small initial increases. We observed minor effects after low-dose Fe and Ni instillation, whereas biphasic changes were noted after high-dose instillations. Combined exposures of ufCB and either Fe or Ni resulted in HRV trends different from values estimated from individual-component effects. CONCLUSIONS: Components in PM may induce different cardioregulatory responses, and a single component may induce different responses during different phases. Concurrent exposure to ufCB and Fe or Ni might introduce interactions on cardioregulatory effects. Also, the effect of PM may be mediated through complex interaction between different components of PM.