Prescription system to calculate precise doses of Chinese herbal medicine to avoid toxic effects.

Background and objectives: Traditional Chinese Medicine (TCM) is a therapeutic system which has been practiced for thousands of years. Although for much of its history the decoction of medicinal herbs was the most common method of consuming the herbal treatments, TCM prescriptions are now primarily prepared using concentrated Chinese herbal extracts (CCHE) in powder or granular form. However, determining the precise dose of each single Chinese herbal constituent within a prescription creates a challenge in clinical practice due to the potential risk of toxicity. To alleviate this, we invented the Chinese Intelligence Prescription System (CIPS) to calculate the exact dose of each single herb within an individual prescription. Methods: In this study, we applied CIPS in a real-world setting to analyze clinical prescriptions collected and prepared at the TCM Pharmacy of China Medical University Hospital (CMUH). Results: Our investigation revealed that 3% of all prescriptions filled in a 1-month period contained inexact dosages, suggesting that more than 170,000 prescriptions filled in Taiwan in a given month may contain potentially toxic components. We further analyzed the data to determine the excess dosages and outline the possible associated side effects. Conclusions: In conclusion, CIPS offers TCM practitioners the ability to prepare exact Chinese herbal medicine (CHM) prescriptions in order to avoid toxic effects, thereby ensuring patient safety.

Effectiveness of Acupuncture for Relieving Chemotherapy-Induced Bone Marrow Suppression: A Systematic Review with a Meta-analysis and Trial Sequential Analysis.

Objective: Bone marrow suppression is the most common side effect of chemotherapy that may lead to discontinuation for treatment pertaining to patients during the therapy course. Acupuncture may relieve bone marrow suppression with regulation hematopoietic function during chemotherapy. The purpose of this study is to evaluate the effectiveness of acupuncture in relieving chemotherapy-induced bone marrow suppression and determine the effects of acupuncture on bone marrow function. Design: PubMed, Embase, Cochrane Library, Medline OVID, CINAHL Plus, Web of Science, and Chinese articles in the Airiti Library and China National Knowledge Infrastructure databases were searched up to February 2023. Publications in both English and Chinese were eligible for inclusion without any limitations on the publication date. Only randomized controlled trials investigating the impact of acupuncture on chemotherapy-induced bone marrow suppression were considered. In addition, a trial sequential analysis was performed to assess the adequacy of the current sample size. Results: A total of 25 studies met the inclusion criteria. Acupuncture was found to increase the levels of hematopoietic cytokine granulocyte colony-stimulating factor (G-CSF) (Hedges' g = 0.79, p < 0.001), as well as stimulate the production of white blood cells (Hedges' g = 0.69, p < 0.001), red blood cells (Hedges' g = 0.37, p = 0.01), neutrophils (Hedges' g = 0.66, p < 0.001), absolute neutrophil count (Hedges' g = 0.89, p = 0.01), hemoglobin (Hb) (Hedges' g = 0.37, p = 0.02), platelets (Hedges' g = 0.50, p < 0.001), and natural killer (NK) cells (Hedges' g = 1.30, p = 0.02). Further, the levels of platelets and NK cells were observed to increase cumulatively over time. Conclusions: Acupuncture may improve chemotherapy-induced bone marrow suppression due to increasing levels of the hematopoietic cytokine, G-CSF and further relieving chemotherapy-induced bone marrow suppression. PROSPERO Registration: This review was registered with PROSPERO (International Prospective Register of Systematic Reviews: CRD42020185813).

Chinese Intelligence Prescription System improves prescription accuracy while decreasing labor and drug costs.

BACKGROUND AND AIM: The traditional method of taking Chinese Medicine involves creating a decoction by cooking medicinal Chinese herbs. However, this method has become less popular, being replaced by the more convenient method of consuming concentrated Chinese herbal extracts, which creates challenges related to the complexity of stacking multiple formulas. METHODS: We developed the Chinese Intelligence Prescription System (CIPS) to simplify the prescription process. In this study, we used data from our institutions pharmacy to calculate the number of reductions, average dispensing time, and resulting cost savings. RESULTS: The mean number of prescriptions was reduced from 8.19 ± 3.65 to 7.37 ± 3.34 ([Formula: see text]). The reduction in the number of prescriptions directly resulted in decreased dispensing time, reducing it from 1.79 ± 0.25 to 1.63 ± 0.66 min ([Formula: see text]). The reduced dispensing time totaled 3.75 h per month per pharmacist, equivalent to an annual labor cost savings of $15,488 NTD per pharmacist. In addition, drug loss was reduced during the prescription process, with a mean savings of $4,517 NTD per year. The combined savings adds up to a not insignificant $20,005 NTD per year per pharmacist. When taking all TCM clinics/hospitals in Taiwan into account, the total annual savings would be $77 million NTD. CONCLUSION: CIPS assists clinicians and pharmacists to formulate precise prescriptions in a clinical setting to simplify the dispensing process while reducing medical resource waste and labor costs.

Experimental Verification for Numerical Simulation of Thalamic Stimulation-Evoked Calcium-Sensitive Fluorescence and Electrophysiology with Self-Assembled Multifunctional Optrode.

Owing to its capacity to eliminate a long-standing methodological limitation, fiber photometry can assist research gaining novel insight into neural systems. Fiber photometry can reveal artifact-free neural activity under deep brain stimulation (DBS). Although evoking neural potential with DBS is an effective method for mediating neural activity and neural function, the relationship between DBS-evoked neural Ca2+ change and DBS-evoked neural electrophysiology remains unknown. Therefore, in this study, a self-assembled optrode was demonstrated as a DBS stimulator and an optical biosensor capable of concurrently recording Ca2+ fluorescence and electrophysiological signals. Before the in vivo experiment, the volume of tissue activated (VTA) was estimated, and the simulated Ca2+ signals were presented using Monte Carlo (MC) simulation to approach the realistic in vivo environment. When VTA and the simulated Ca2+ signals were combined, the distribution of simulated Ca2+ fluorescence signals matched the VTA region. In addition, the in vivo experiment revealed a correlation between the local field potential (LFP) and the Ca2+ fluorescence signal in the evoked region, revealing the relationship between electrophysiology and the performance of neural Ca2+ concentration behavior. Concurrent with the VTA volume, simulated Ca2+ intensity, and the in vivo experiment, these data suggested that the behavior of neural electrophysiology was consistent with the phenomenon of Ca2+ influx to neurons.

Proof of Concept for Sustainable Manufacturing of Neural Electrode Array for In Vivo Recording.

Increasing requirements for neural implantation are helping to expand our understanding of nervous systems and generate new developmental approaches. It is thanks to advanced semiconductor technologies that we can achieve the high-density complementary metal-oxide-semiconductor electrode array for the improvement of the quantity and quality of neural recordings. Although the microfabricated neural implantable device holds much promise in the biosensing field, there are some significant technological challenges. The most advanced neural implantable device relies on complex semiconductor manufacturing processes, which are required for the use of expensive masks and specific clean room facilities. In addition, these processes based on a conventional photolithography technique are suitable for mass production, which is not applicable for custom-made manufacturing in response to individual experimental requirements. The microfabricated complexity of the implantable neural device is increasing, as is the associated energy consumption, and corresponding emissions of carbon dioxide and other greenhouse gases, resulting in environmental deterioration. Herein, we developed a fabless fabricated process for a neural electrode array that was simple, fast, sustainable, and customizable. An effective strategy to produce conductive patterns as the redistribution layers (RDLs) includes implementing microelectrodes, traces, and bonding pads onto the polyimide (PI) substrate by laser micromachining techniques combined with the drop coating of the silver glue to stack the laser grooving lines. The process of electroplating platinum on the RDLs was performed to increase corresponding conductivity. Sequentially, Parylene C was deposited onto the PI substrate to form the insulation layer for the protection of inner RDLs. Following the deposition of Parylene C, the via holes over microelectrodes and the corresponding probe shape of the neural electrode array was also etched by laser micromachining. To increase the neural recording capability, three-dimensional microelectrodes with a high surface area were formed by electroplating gold. Our eco-electrode array showed reliable electrical characteristics of impedance under harsh cyclic bending conditions of over 90 degrees. For in vivo application, our flexible neural electrode array demonstrated more stable and higher neural recording quality and better biocompatibility as well during the 2-week implantation compared with those of the silicon-based neural electrode array. In this study, our proposed eco-manufacturing process for fabricating the neural electrode array reduced 63 times of carbon emissions compared to the traditional semiconductor manufacturing process and provided freedom in the customized design of the implantable electronic devices as well.

Relationship of spirituality, health engagement, health belief and attitudes toward acceptance and willingness to pay for a COVID-19 vaccine.

PURPOSE: To explore the wider determinant factor of citizens' spirituality, health engagement, health belief model, and attitudes towards vaccines toward acceptance and willingness to pay for a Coronavirus disease 2019 (COVID-19) vaccination. METHODS: A community-based cross-sectional online investigation with convenience sampling was utilized to recruit 1423 citizens from 18 districts across Indonesia between December 14, 2020 and January 17, 2021. Descriptive statistics, One-way analysis of variance, Pearson correlation, Independent t-tests, and multiple linear regression were examined. RESULTS: Spirituality, health engagement and attitude toward vaccines, as well as health beliefs constructs (all scores of perceived benefits and barriers) were significant key factors of acceptance of vaccines. Interestingly, the spirituality, attitude toward vaccine, and health beliefs constructs including perceived susceptibility, and benefits indicated a significantly higher willingness. CONCLUSIONS: Results demonstrated the utility of spirituality, health engagement, health belief model, and attitudes towards vaccines in understanding acceptance and willingness to pay for a vaccine. Specifically, a key obstacle to the acceptance of and willingness to pay COVID-19 vaccination included a high score of the perceived barrier construct. Moreover, the acceptance of and willingness to pay could be impaired by worries about the side-effects of a COVID-19 vaccination.

Attenuation of in vitro and in vivo melanin synthesis using a Chinese herbal medicine through the inhibition of tyrosinase activity.

BACKGROUND: In traditional Chinese medicine, the skin reflects the health of body organs. A skin whitening agent, named seven whitening creams (also called Chi-Bai-San), has been used since ancient times in China. Chi-Bai-San reduces melanin and helps to reduce wrinkles. PURPOSE: We aimed to determine the skin-whitening ability and safe dose of the seven compounds in Chi-Bai-San. STUDY DESIGN: A common use for Chinese medicine is decocted in water. To mimic the function of Chi-Bai-San apply in clinical, we boiled all seven compound in water, respectively. These single recipe extractions and a mixture of these seven items were used in zebrafish embryo and B16F10 melanoma cell to identify the anti-melanogenesis function. METHODS: Chi-Bai-San comprises Bai-Lian (Ampelopsis japonica), Bai-Ji (Bletilla striata), Bai-Zhi (Angelica dahurica), Bai-Zhu (Atractylodes macrocephala), Bai-Shau (Paeonia lactiflora), Fu-Ling (Wolfiporia cocos), and Jen-Ju-Fen (Pearl powder). All components were extracted by heating in distilled water. The supernatant was collected after centrifugation. The extracted components were introduced into zebrafish embryos at different doses to determine the safe dose. B16F10 melanoma cells were treated with the final dose of each component and the component mixture. Melanin content and tyrosinase activity were assessed in zebrafish and B16F10 cells. Chi-Bai-San and its components were exposed to α MSH-induced B16F10 cells, and detected for mechanism of anti-melanogenesis pathway. RESULTS: Most compounds were not toxic at a low dose (0.1 mg/ml), except A. macrocephala, which resulted in a survival rate of only 30% at 72 hpf. The final dose of A. dahurica, P. lactiflora, W. cocos, and pearl was 1 mg/ml; that of A. japonica was 0.5 mg/ml; and that of A. macrocephala and B. striata was 0.1 mg/ml. Chi-Bai-San markedly decreased melanin content 37.47% in zebrafish embryos. Further, Chi-Bai-San abolished tyrosinase activity and MITF-mediated tyrosinase expression by down regulating the upstream transcription factors ZEB2, ß-catenin, and CREB2 in α MSH-induced B16F10 cells. Additionally, Chi-Bai-San might reduce melanosome secretion from melanocytes. CONCLUSION: Our findings indicate that safety and efficacy of heat-extracted Chi-Bai-San, which can reduce αMSH-induced melanin production by inhibiting the key role of melogenic-related transcription factor and promote the synergic effect of seven types of traditional Chinese herbal medicines.

Uncovering the Modulatory Interactions of Brain Networks in Cognition with Central Thalamic Deep Brain Stimulation Using Functional Magnetic Resonance Imaging.

Deep brain stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. It acts by altering brain networks and facilitating synaptic plasticity. For enhancing cognitive functions, the central thalamus (CT) has been shown to be a potential DBS target. The network-level mechanisms contributing to the effect exerted by DBS on the CT (CT-DBS) remain unknown. Combining CT-DBS with functional magnetic resonance imaging (fMRI), this study explored brain areas activated while applying CT-DBS in rats, using a newly developed neural probe that was compatible with MRI and could minimize the image distortion and resolve safety issues. Results showed activation of the anterior cingulate cortex, motor cortex, primary and secondary somatosensory cortices, caudate putamen, hypothalamus, thalamus, and hippocampus, suggesting that the corticostriatal, corticolimbic, and thalamocortical brain networks were affected. Behaviorally, the CT-DBS group required a shorter time than sham controls to learn a water-reward lever-pressing task and made more correct choices in a T-maze task. Concurrent with enhanced learning performance, bilateral CT-DBS resulted in alteration in the functional connectivity of brain networks determined by resting-state fMRI. Western blot analyses showed that the protein level of both dopamine D1 and α4-nicotinic acetylcholine receptors was increased, and dopamine D2 receptor was decreased. These data suggest that CT-DBS can enhance cognitive performance as well as brain connectivity through the modulation of synaptic plasticity, such that CT is a target providing high potential for the remediation of acquired cognitive learning and memory disabilities.

Adlay Bran Oil Suppresses Hepatic Gluconeogenesis and Attenuates Hyperlipidemia in Type 2 Diabetes Rats.

This study aimed to examine the antidiabetic effects of various concentrations of adlay bran oil (ABO) in high fat diet and streptozotocin-induced diabetic rats. Dietary supplementation with 10% ABO for 4 weeks effectively decreased the blood triacylglycerol, glucose, and total cholesterol levels in diabetic rats, although body weight remained the same. The mRNA and protein expressions of hepatic glucose transporter 2 (GLUT-2) and phosphoenolpyruvate carboxykinase (PEPCK) were increased and that of glucokinase (GCK) were decreased in diabetic rats. However, 10% ABO treatment reduced the mRNA and protein expressions of GLUT-2 and PEPCK and elevated the expression of hepatic GCK in diabetic rats. Thus, ABO enhanced hepatic glucose metabolism to decrease blood glucose in diabetic rats. In addition, 10% ABO supplementation increased the expression of phosphorylated protein kinase B (Akt) relative to the total Akt levels in the muscles of diabetic rats, indicating enhanced insulin sensitivity. The results indicate that ABO displays a potential for improving hyperlipidemia and hyperglycemia in diabetes by enhancing insulin sensitivity and hepatic glucose metabolism.

Significant Effect of Acupressure in Elevating Blood Stem Cell Factor During Chemotherapy in Patients With Gynecologic Cancer.

BACKGROUND: Chemotherapy is used mainly to treat and control the progression of gynecological cancer. Bone marrow suppression, one of the adverse side effects of chemotherapy, may decrease immune function, increasing the risk of serious, fatal infections. PURPOSE: The aims of this study were to evaluate the effectiveness of noninvasive acupressure in preventing and diminishing chemotherapy-induced myelosuppression in patients with gynecologic cancer and to determine whether this effect is associated with the regulation of the expressions of granulocyte-macrophage colony-stimulating factor and stem cell factor (SCF). METHODS: In total, 28 women with gynecological cancer were randomly assigned either to the experimental group (n = 10) or to the control group (n = 18). The experimental group received acupressure of 5-minute duration to the Hegu (LI4), Quchi (LI11), Xuehai (SP10), Sanyinjiao (SP6), Taixi (K3), Zusanli (ST36), Taichong (LR3), and Baihui (GV20) points, respectively, three times per day for 6 weeks. The control group did not receive the acupressure intervention. The blood count, including white blood cells, platelets, and hemoglobin, and serum levels for SCF and granulocyte-macrophage colony-stimulating factor were assessed before (pretest) and 6 weeks after (posttest) the participants' first course of chemotherapy. RESULTS: At posttest, blood hemoglobin had significantly decreased from (mean ± SD) 11.6 ± 2.2 to 10.8 ±1.6 mg/dl (p = .03) in the control group. However, no significant pretest-posttest difference in hemoglobin concentration (11.4 ± 1.0 vs. 10.9 ± 1.1 mg/dl) was detected in the experimental group. Levels of SCF increased significantly between pretest and posttest in both the control group (from 1196.10 ± 293.17 to 1325.05 ± 253.77 ng/ml; p = .01) and the acupressure group (from 1046.78 ± 469.52 to 1387.06 ± 310.00 ng/ml; p = .007). In addition, a borderline difference (p = .05) in mean pretest-posttest SCF increase was found between the acupressure group (340.28 ± 255.46 ng/ml) and the control group (128.94 ± 250.64 ng/ml). Finally, a significant time-dependent interactive effect was found between acupressure and the increased blood level of SCF at posttest (ß = 211.34, p = .02). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings support that acupressure on specific acupoints increases blood SCF levels significantly, which may help protect chemotherapy patients from experiencing reduced hemoglobin levels and may relieve chemotherapy-induced myelosuppression in patients with gynecologic cancer. This noninvasive approach is suggested for practical implementation in patients undergoing a course of chemotherapy.

Association of Activation of Induced COX-2, iNOS and Cytokines with NF-kappa B Depression by Taiwan Wild Grape Ethanolic Extract in Mice.

Taiwan wild grape (Vitis thunbergii var. taiwaniana; VTT) is an important traditional herbal medicine used to treat muscle injuries and acute and chronic pain of the ligaments. Information on its bioactivity and the underlying mechanisms, which have not been elucidated thus far, is needed to demonstrate its value for pharmacological and clinical use. This study presents evidence to clarify the antinociceptive and anti-inflammatory activities of an ethanolic extract of VTT stem (VTTEtOH) and the possible molecular mechanisms involved in such biactivities. In the mice, VTTEtOH significantly reduced the acetic acid-induced writhing response (P < 0.01), formalin-induced licking time (P < 0.01), and edema paw volume at 4 and 5 h after λ-carrageenan injection. VTTEtOH obviously decreased the levels of tumor necrosis factor alpha (P < 0.01), interleukin (IL)-1ß (P < 0.05), interleukin (IL)-6 (P < 0.001), nuclear factor-kappa B (P < 0.001), iNOS (P < 0.001), cyclooxygenase-2 (P < 0.001) and Nitric oxide (P < 0.001) in edema-paw tissue. The molecular mechanisms underlying these effects might involve significant inhibition of the activity of cyclooxygenase-2 through suppression of nuclear factor-kappa B and inducible nitric oxide synthase expression and reduction of the levels of various inflammatory mediators, including tumor necrosis factor alpha, interleukin (IL)-1ß, IL-6, and nitric oxide. Our findings provided pharmacological and histopathological evidences that VTTEtOH alleviates inflammatory pain-related diseases.

Antitussive, anti-pyretic and toxicological evaluation of Ma-Xing-Gan-Shi-Tang in rodents.

BACKGROUND: Ma-Xing-Gan-Shi-Tang (abbreviated as MXGST), an important Chinese herbal prescribed for cough, bronchial inflammation and fever from pneumonia, consists of four medicinal herbs, including Ephedrae herb, Semen Pruni Armeniacae, licorice and Gypsum. These components, especially Ephedrae and Semen Pruni Armeniacae, possess antitussive activities, but they have severe adverse effects. METHODS: The pharmacological activities of MXGST extract in clinical use were investigated with citric acid-induced cough, acetylcholine/histamine-induced bronchial contraction and lipopolysaccharide (LPS)-induced fever in rodents. The subacute toxicology of MXGST extract was evaluated after a 28-day repeated oral administration in rats. RESULTS: Each gram of MXGST extract contained 60 ± 8 µg of ephedrine, 480 ± 40 µg of glycyrrhizic acid and 440 ± 8 µg of amygdalin according to high performance liquid chromatography and a photodiode array detector. MXGST extract produced pronounced, dose-dependent antitussive effects in guinea pigs and reduced hyperthermic syndrome induced by LPS in rats. MXGST extract blocked the bronchial contraction induced by acetylcholine/histamine. Oral administration of MXGST extract for 28 days did not cause any hematological, biochemical or histological changes in rats. CONCLUSIONS: MXGST extract is a safer, more effective Chinese prescription with antitussive and anti-pyretic effects. The antitussive mechanism of MXGST is related to partially relaxing the bronchial smooth muscle by blocking acetylcholinergic and histaminergic receptors.

Efficacy of Femarelle for the treatment of climacteric syndrome in postmenopausal women: An open label trial.

OBJECTIVE: To assess the effects of 2 months of treatment with Femarelle for climacteric syndrome in Taiwanese postmenopausal women. MATERIALS AND METHODS: A multi-center, open-label trial of 260 postmenopausal women, age ≥ 45 years with vasomotor symptoms. Women were enrolled after obtaining a detailed medical history and a thorough physical examination. They then received Femarelle (640 mg/d) twice daily for 8 weeks. The primary outcome was the changes in the frequency and severity of hot flushes from baseline to 4 weeks (1 month) and 8 weeks (2 months). Changes of general climacteric syndrome were assessed using a modified climacteric scale designed by Greene. RESULTS: The frequency and severity of hot flushes were significantly improved with Femarelle use (p < 0.001). After 8 weeks of treatment, the percentage of women with various climacteric syndromes was reduced (from 100% to 20.9% for hot flushes, from 97.7% to 87.9% for psychological symptoms, from 93.8% to 78.8% for somatic symptoms, and from 87.8% to 74.9% for sexual symptoms). General climacteric syndrome scores also significantly decreased, from 20.8 ± 0.7 at the time of enrollment to 12.9 ± 0.7 after 8 weeks of Femarelle treatment (p < 0.0001). Participants experienced improvement of various climacteric symptoms and signs after 8 weeks of treatment (75.1% for hot flushes, 68.7% for psychological symptoms, 70.6% for somatic symptoms, and 69.0% for sexual problems respectively). After 4 weeks and 8 weeks of treatment with Femarelle, patients showed statistically significant improvement in climacteric symptoms (p < 0.0001). Three women (1.2%) withdrew from the study after 4 weeks of treatment due to adverse effects. CONCLUSION: Femarelle significantly improved climacteric symptoms in Taiwanese postmenopausal women. However, further evaluation is needed regarding the safety of long-term consumption.

Anti-nociceptive, anti-inflammatory and toxicological evaluation of Fang-Ji-Huang-Qi-Tang in rodents.

BACKGROUND: Fang-Ji-Huang-Qi-Tang (abbreviated as FJHQT), composed by six medicinal herbs including Radix Stephania Tetrandra, Radix Astragali, Rhizoma Atractylodis Macrocephalae, Radix Glycyrrhizae, Rhizoma Zingiberis and Fructus Ziziphi Jujubae, is a frequently Chinese prescription for treating painful and inflammatory disorders such as rheumatoid arthritis. When Radix Stephania Tetrandra was misused with Aristolochia species, acute or chronic nephropathy caused by aristolochic acid was happened. Thus, the present study was aimed to identify Radix Stephania Tetrandra and performed the pharmacological and toxicological evaluation of FJHQT extract in rodents. METHODS: Radix Stephania Tetrandra was identified by macroscopic and microscopic observation, and the content of tetrandrine in FJHQT extract was measured by high performance liquid chromatography. Then, the pharmacological activities of FJHQT extract with respect to clinical use was investigated with acetic acid-induced writhing response, formalin-induced licking response and carrageenan-induced paw edema. Finally, we evaluated the subacute toxicology of FJHQT extract after 28-day repeated oral administration in rats. RESULTS: Radix Stephania Tetrandra was correctly used in FJHQT extract, and the content of tetrandrine in FJHQT extract was 2.5 mg/g. FJHQT extract produced a pronounced and dose-dependent antinociceptive and anti-inflammatory effects in three above models. FJHQT extract after 28-day repeated administration did not caused any hematological, biochemical and histological change in rats. CONCLUSIONS: We suggest that FJHQT extract is a high safety index Chinese medicine for antinociceptive and anti-inflammatory application when Radix Stephania Tetrandra was correctly used in FJHQT. Its antinociceptive and anti-inflammatory mechanism might be related to peripheral nociceptive pathway such as prostaglandins.

Active Component of Antrodia cinnamomea Mycelia Targeting Head and Neck Cancer Initiating Cells through Exaggerated Autophagic Cell Death.

Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer. Previously, we identify head and neck cancer initiating cells (HN-CICs), which are highly tumorigenic and resistant to conventional therapy. Therefore, development of drug candidates that effectively target HN-CICs would benefit future head and neck cancer therapy. In this study, we first successfully screened for an active component, named YMGKI-1, from natural products of Antrodia cinnamomea Mycelia (ACM), which can target the stemness properties of HNSCC. Treatment of YMGKI-1 significantly downregulated the aldehyde dehydrogenase (ALDH) activity, one of the characteristics of CIC in HNSCC cells. Additionally, the tumorigenic properties of HNSCC cells were attenuated by YMGKI-1 treatment in vivo. Further, the stemness properties of HN-CICs, which are responsible for the malignancy of HNSCC, were also diminished by YMGKI-1 treatment. Strikingly, YMGKI-1 also effectively suppressed the cell viability of HN-CICs but not normal stem cells. Finally, YMGKI-1 induces the cell death of HN-CICs by dysregulating the exaggerated autophagic signaling pathways. Together, our results indicate that YMGKI-1 successfully lessens stemness properties and tumorigenicity of HN-CICs. These findings provide a new drug candidate from purified components of ACM as an alternative therapy for head and neck cancer in the future.

Analgesic and Anti-Inflammatory Activities of Methanol Extract of Cissus repens in Mice.

The aim of this study was to investigate possible analgesic and anti-inflammatory mechanisms of the CR(MeOH). Analgesic effect was evaluated in two models including acetic acid-induced writhing response and formalin-induced paw licking. The anti-inflammatory effect was evaluated by λ-carrageenan-induced mouse paw edema and histopathologic analyses. The results showed that CR(MeOH) (500 mg/kg) decreased writhing response in the acetic acid assay and licking time in the formalin test. CR(MeOH) (100 and 500 mg/kg) significantly decreased edema paw volume at 4th to 5th hours after λ-carrageenan had been injected. Histopathologically, CR(MeOH) abated the level of tissue destruction and swelling of the edema paws. These results were indicated that anti-inflammatory mechanism of CR(MeOH) may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx, and GRd in the liver. Additionally, CR(MeOH) also decreased IL-1ß, IL-6, NFκB, TNF-α, COX-2, and iNOS levels. The contents of two active ingredients, ursolic acid and lupeol, were quantitatively determined. This paper demonstrated possible mechanisms for the analgesic and anti-inflammatory effects of CR(MeOH) and provided evidence for the classical treatment of Cissus repens in inflammatory diseases.

Antidepressant-Like Activity of the Ethanolic Extract from Uncaria lanosa Wallich var. appendiculata Ridsd in the Forced Swimming Test and in the Tail Suspension Test in Mice.

This study investigated the antidepressant activity of ethanolic extract of U. lanosa Wallich var. appendiculata Ridsd (UL(EtOH)) for two-weeks administrations by using FST and TST on mice. In order to understand the probable mechanism of antidepressant-like activity of UL(EtOH) in FST and TST, the researchers measured the levels of monoamines and monoamine oxidase activities in mice brain, and combined the antidepressant drugs (fluoxetine, imipramine, maprotiline, clorgyline, bupropion and ketanserin). Lastly, the researchers analyzed the content of RHY in the UL(EtOH). The results showed that UL(EtOH) exhibited antidepressant-like activity in FST and TST in mice. UL(EtOH) increased the levels of 5-HT and 5-HIAA in cortex, striatum, hippocampus, and hypothalamus, the levels of NE and MHPG in cortex and hippocampus, the level of NE in striatum, and the level of DOPAC in striatum. Two-week injection of IMI, CLO, FLU and KET enhanced the antidepressant-like activity of UL(EtOH). UL(EtOH) inhibited the activity of MAO-A. The amount of RHY in UL(EtOH) was 17.12 mg/g extract. Our findings support the view that UL(EtOH) exerts antidepressant-like activity. The antidepressant-like mechanism of UL(EtOH) may be related to the increase in monoamines levels in the hippocampus, cortex, striatum, and hypothalamus of mice.

Analgesic and Anti-Inflammatory Activities of the Ethanolic Extract of Artemisia morrisonensis Hayata in Mice.

The aim of this study was to investigate the possible analgesic and anti-inflammatory mechanisms of the ethanolic extract of A. morrisonensis Hayata (AM(EtOH)). Two models were employed for evaluation of the analgesic effects: acetic acid-induced writhing response and formalin-induced paw licking. The results demonstrated that AM(EtOH) decreased writhing response for both the acetic acid assay and the licking time in the formalin test. The anti-inflammatory effect was evaluated by paw edema of mice induced by λ-carrageenan. AM(EtOH) significantly decreased induced paw edema three to four hours after λ-carrageenan injection. Additionally, the results indicated that the anti-inflammatory mechanism of AM(EtOH) may be due to the declined levels of nitric oxide (NO) and malondialdehyde (MDA) in the edematous paw. Furthermore, AM(EtOH) decreased the tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, leading to the reduction of prostaglandins and subsequently alleviated edema. Isolation and purification of the AM(EtOH) extract determined p-hydroxyacetophenone to be a major component at 130 mg/g of extract. No mortality was observed in the acute toxicity test given at the dose of 10 g/kg. This study demonstrated the possible mechanisms for the analgesic and anti-inflammatory effects of AM(EtOH) for mice and provided evidence for the ethnobotanical uses of A. morrisonensis in treating inflammatory diseases.

Care needs of older patients in the intensive care units.

AIMS: To explore the care needs of older patients in the intensive care units. Background. As the numbers of older patients admitted to the intensive care units are growing, care quality of critically ill older patients has become an important issue. However, there are few studies directly investigating perceived care needs of hospitalised older patients and the studies on care needs of older patients in the intensive care units are even fewer. The identification of care needs from older patients' perspective will help develop qualified nursing practice. DESIGN: A qualitative exploratory design. METHODS: Purposive sampling was performed to recruit 35 older patients from three hospitals in Taiwan. The interview transcripts were analysed by qualitative content analysis. RESULTS: The results revealed that care needs of older patients in the intensive care units are multidimensional, including physical, informational and psychosocial dimensions. Older patients' needs of the physical dimension included relieving pain and discomfort, starting oral intake as soon as possible and having continuous sleep. Informational needs included adequate explanations about their disease progression and prognosis and information on recovery-promoting activity. Psychosocial needs included caring behaviour of intensive care units staff, flexible visiting hours, increase in control ability and maintenance of good communication with intensive care units staff. CONCLUSION: The findings can assist nurses in understanding the interventions necessary to meet care needs of critically ill older patients. The critically ill older adults need more than medical-technical care. They need more holistic care. The psychosocial and informational needs must be considered commensurate with the presenting physical needs. RELEVANCE TO CLINICAL PRACTICE: Nurses have an important role in meeting intensive care units older patients' care needs. Intensive care units nurses should conduct comprehensive assessment regarding older patients' needs at the beginning and at various points in their intensive care units stay and match these needs with appropriate nursing interventions.

Antibacterial activities of plant essential oils against Legionella pneumophila.

The objective of this study was to determine the antimicrobial activity of essential oils (EOs) extracted from Cinnamomum osmophloeum leaves and different tissues of Cryptomeria japonica against pathogenic Legionella pneumophila at 42 degrees C. Ten kinds of EOs were extracted by water distillation and their chemical constituents were quantified by gas chromatography-mass spectroscopy (GC-MS). The results showed that cinnamon leaf EO possessed stronger anti-L. pneumophila activity than C. japonica EO. In particular, the highest bactericidal effect was noted in contact with C. osmophloeum leaf EO of cinnamaldehyde type (characterized by its major constituent of cinnamaldehyde accounting for 91.3% of EO), regardless of contacted cell concentration (2 and 4 log CFU ml(-1)) or exposure time (10 and 60 min). Cinnamaldehyde is responsible for anti-L. pneumophila activity based on the results of antimicrobial testing and statistical analysis. Stepwise regression analyses show that EO concentration is the most significant factor affecting the bioactivity of EO. It is concluded that C. osmophloeum leaf oil of cinnamaldehyde type and its major constituent, cinnamaldehyde, possess strong anti-L. pneumophila activities, and have the great potential to be used as an antibacterial agent to control legionellosis associated with hot tubs and spa facilities widely used in homes and resorts.