Psychophysiological and emotional effects of human-Dog interactions by activity type: An electroencephalogram study.

Animal-assisted interventions are being increasingly used in studies that support various health effects. This study compared the psychophysiological and emotional responses during diverse activities with a dog to understand the impact of activity type. This study included 30 healthy adults (average age: 27.9 ± 8.4 years). Participants performed eight different activities with a dog for 3 minutes each. These activities included meeting, playing, feeding, massaging, grooming, photographing, hugging, and walking. Brain waves in the prefrontal, frontal, parietal, and occipital lobes were measured during the activities. Subjective evaluation of their emotions was recorded after each activity via the Profile of Mood States, Semantic Differential Method, and Stress Numeric Rating Scale. The alpha (relative, relative slow, relative fast) power spectra indicated that the brain's relaxation and resting state significantly increased when playing with and walking a dog. The beta (relative, relative low, and relative mid) power spectra significantly increased during dog massage, grooming, and playing activities, indicating improved concentration without stress. Notably, playing with a dog positively affected both relaxation and concentration. The Profile of Mood States outcome showed that activities such as feeding, massaging, and hugging the dog decreased the total mood disorder score, which indicated a positive effect on participants' moods. The Semantic Differential Method revealed that participants felt comfortable and natural while walking with a dog and relaxed when massaging it. Participants showed significantly lower stress moods in all the activities. This study demonstrated that specific dog activities could activate stronger relaxation, emotional stability, attention, concentration, and creativity by facilitating increased brain activity. In addition, interactions with dogs could decrease stress and induce positive emotional responses. These results provide data that forms the basis for the composition of the AAI program and may be applicable as a reference to determine the most effective activities for specific applications.

[Mechanism of n-butanol fraction of Wenxia Formula combining with gefitinib in treating non-small cell lung cancer based on network pharmacology and in vitro experiment].

This study combined network pharmacology, molecular docking, and in vitro experiments to explore the potential mechanism of the active components of the n-butanol fraction of Wenxia Formula(NWXF) combined with gefitinib(GEF) in treating non-small cell lung cancer(NSCLC). Ultra-performance liquid chromatography-quadrupole Orbitrap mass spectrometry(UPLC-Q-Orbitrap MS) was employed to detect the main chemical components of NWXF. The active components of NWXF were retrieved from SwissADME, and the candidate targets of these active components were retrieved from SwissTargetPrediction. Online Mendelian Inheritance in Man(OMIM) and GeneCards were searched for the targets of NSCLC. Cytoscape 3.9.0 and STRING were employed to build the protein-protein interaction(PPI) network with the common targets shared by NWXF and NSCLC. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment were performed in DAVID to predict the potential mechanisms. Finally, molecular docking between the main active ingredients and key targets was conducted in SYBYL-X 2.0. The methyl thiazolyl tetrazolium(MTT) assay was employed to evaluate the inhibitory effects of NWXF and/or GEF on the proliferation of human non-small cell lung cancer cells(A549 and PC-9). Additionally, the impact of NWXF on human embryonic lung fibroblast cells(MRC-5) was assessed. The effectiveness of the drug combination was evaluated based on the Q value. The terminal-deoxynucleoitidyl transferase mediated nick-end labeling(TUNEL) assay was employed to examine the apoptosis of A549 and PC-9 cells treated with NWXF and/or GEF. Quantitative real-time PCR(qRT-PCR) was employed to measure the mRNA levels of epidermal growth factor receptor(EGFR), c-Jun N-terminal kinase(JNK), and Bcl2-associated X protein(Bax) in the A549 and PC-9 cells treated with NWXF and/or GEF. Western blot was employed to determine the protein levels of EGFR, p-EGFR, JNK, p-JNK, and Bax in the A549 and PC-9 cells treated with NWXF and/or GEF. A total of 77 active components, 488 potential targets, and 49 key targets involved in the treatment of NSCLC with NWXF were predicted. The results of GO annotation showed that NWXF may treat NSCLC by regulating the biological processes such as cell proliferation, apoptosis, and protein phosphorylation. KEGG enrichment revealed that the key targets of NWXF in treating NSCLC were enriched in the mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT), hypoxia-inducible factor-1(HIF-1), and microRNA-related signaling pathways. Molecular docking results showed that 91.9% of the docking scores were greater than 5, indicating the strong binding capability between main active components and key targets. The cell experiments demonstrated that NWXF combined with GEF synergistically inhibited the proliferation, promoted the apoptosis, decreased p-EGFR/EGFR and p-JNK/JNK values, down-regulated the mRNA levels of EGFR and JNK, and up-regulated the mRNA and protein levels of Bax in A549 and PC-9 cells. In conclusion, NWXF combined with GEF can regulate the EGFR/JNK pathway to promote the apoptosis of NSCLC cells, thus treating NSCLC.

Fangchinoline derivatives inhibits PI3K signaling in vitro and in vivo in non-small cell lung cancer.

Fangchinoline (Fan) are extracted from the traditional Chinese medicine Stephania tetrandra S., which is a bis-benzyl isoquinoline alkaloids with anti-tumor activity. Therefore, 25 novel Fan derivatives have been synthesized and evaluated for their anti-cancer activity. In CCK-8 assay, these fangchinoline derivatives displayed higher proliferation inhibitory activity on six tumor cell lines than the parental compound. Compared to the parent Fan, compound 2h presented the anticancer activity against most cancer cells, especially A549 cells, with an IC50 value of 0.26 µM, which was 36.38-fold, and 10.61-fold more active than Fan and HCPT, respectively. Encouragingly, compound 2h showed low biotoxicity to the human normal epithelial cell BEAS-2b with an IC50 value of 27.05 µM. The results indicated compound 2h remarkably inhibited the cell migration by decreasing MMP-2 and MMP-9 expression and inhibited the proliferation of A549 cells by arresting the G2/M cell cycle. Meanwhile, compound 2h could also induce A549 cell apoptosis by promoting endogenous pathways of mitochondrial regulation. In nude mice presented that the growth of tumor tissues was markedly inhibited by the consumption of compound 2h in a dose-dependent manner, and it was found that compound 2h could inhibit the mTOR/PI3K/AKT pathway in vivo. In docking analysis, high affinity interaction between 2h and PI3K was responsible for drastic kinase inhibition by the compound. To conclude, this derivative compound may be useful as a potent anti-cancer agent for treatment of NSCLC.

Protocol for a bandit-based response adaptive trial to evaluate the effectiveness of brief self-guided digital interventions for reducing psychological distress in university students: the Vibe Up study.

INTRODUCTION: Meta-analytical evidence confirms a range of interventions, including mindfulness, physical activity and sleep hygiene, can reduce psychological distress in university students. However, it is unclear which intervention is most effective. Artificial intelligence (AI)-driven adaptive trials may be an efficient method to determine what works best and for whom. The primary purpose of the study is to rank the effectiveness of mindfulness, physical activity, sleep hygiene and an active control on reducing distress, using a multiarm contextual bandit-based AI-adaptive trial method. Furthermore, the study will explore which interventions have the largest effect for students with different levels of baseline distress severity. METHODS AND ANALYSIS: The Vibe Up study is a pragmatically oriented, decentralised AI-adaptive group sequential randomised controlled trial comparing the effectiveness of one of three brief, 2-week digital self-guided interventions (mindfulness, physical activity or sleep hygiene) or active control (ecological momentary assessment) in reducing self-reported psychological distress in Australian university students. The adaptive trial methodology involves up to 12 sequential mini-trials that allow for the optimisation of allocation ratios. The primary outcome is change in psychological distress (Depression, Anxiety and Stress Scale, 21-item version, DASS-21 total score) from preintervention to postintervention. Secondary outcomes include change in physical activity, sleep quality and mindfulness from preintervention to postintervention. Planned contrasts will compare the four groups (ie, the three intervention and control) using self-reported psychological distress at prespecified time points for interim analyses. The study aims to determine the best performing intervention, as well as ranking of other interventions. ETHICS AND DISSEMINATION: Ethical approval was sought and obtained from the UNSW Sydney Human Research Ethics Committee (HREC A, HC200466). A trial protocol adhering to the requirements of the Guideline for Good Clinical Practice was prepared for and approved by the Sponsor, UNSW Sydney (Protocol number: HC200466_CTP). TRIAL REGISTRATION NUMBER: ACTRN12621001223820.

Optimisation of the Extraction Process of Naringin and Its Effect on Reducing Blood Lipid Levels In Vitro.

The naringin extraction process was optimised using response surface methodology (RSM). A central component design was adopted, which included four parameters: extraction temperature (X1), material-liquid ratio (X2), extraction time (X3), and ultrasonic frequency (X4) of 74.79 °C, 1.58 h, 1:56.51 g/mL, and 28.05 KHz, respectively. Based on these optimal extraction conditions, naringin was tested to verify the model's accuracy. Naringin yield was 36.2502 mg/g, which was equivalent to the predicted yield of 36.0124 mg/g. DM101 macroporous adsorption resin was used to purify naringin. The effects of loading concentration, loading flow rate, and sample pH on the adsorption rate of naringin and the effect of ethanol concentration on the desorption rate of naringin were investigated. The optimum conditions for naringin purification using macroporous resins were determined. The optimal loading concentration, sample solution pH, and loading flow rate were 0.075 mg/mL, 3.5, and 1.5 mL/min, respectively. Three parallel tests were conducted under these conditions, and the average naringin yield was 77.5643%. Naringin's structure was identified using infrared spectroscopy and nuclear magnetic resonance. In vitro determination of the lipid-lowering activity of naringin was also conducted. These results showed that naringin has potential applications as a functional food for lowering blood lipid levels.

Improved colonic inflammation by nervonic acid via inhibition of NF-κB signaling pathway of DSS-induced colitis mice.

BACKGROUND: Nervonic acid (C24:1∆15, 24:1 ω-9, cis-tetracos-15-enoic acid; NA), a long-chain monounsaturated fatty acid, plays an essential role in prevention of metabolic diseases, and immune regulation, and has anti-inflammatory properties. As a chronic, immune-mediated inflammatory disease, ulcerative colitis (UC) can affect the large intestine. The influences of NA on UC are largely unknown. PURPOSE: The present study aimed to decipher the anti-UC effect of NA in the mouse colitis model. Specifically, we wanted to explore whether NA can regulate the levels of inflammatory factors in RAW264.7 cells and mouse colitis model. METHODS: To address the above issues, the RAW264.7 cell inflammation model was established by lipopolysaccharide (LPS), then the inflammatory factors tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß), and Interleukin-10 (IL-10) were detected by Enzyme-linked immunosorbent assay (ELISA). The therapeutic effects of NA for UC were evaluated using C57BL/6 mice gavaged dextran sodium sulfate (DSS). Hematoxylin and eosin (H&E) staining, Myeloperoxidase (MPO) kit assay, ELISA, immunofluorescence assay, and LC-MS/MS were used to assess histological changes, MPO levels, inflammatory factors release, expression and distribution of intestinal tight junction (TJ) protein ZO-1, and metabolic pathways, respectively. The levels of proteins involved in the nuclear factor kappa-B (NF-κB) pathway in the UC were investigated by western blotting and RT-qPCR. RESULTS: In vitro experiments verified that NA could reduce inflammatory response and inhibit the activation of key signal pathways associated with inflammation in LPS-induced RAW264.7 cells. Further, results from the mouse colitis model suggested that NA could restore intestinal barrier function and suppress NF-κB signal pathways to ameliorate DSS-induced colitis. In addition, untargeted metabolomics analysis of NA protection against UC found that NA protected mice from colitis by regulating citrate cycle, amino acid metabolism, pyrimidine and purine metabolism. CONCLUSION: These results suggested that NA could ameliorate the secretion of inflammatory factors, suppress the NF-κB signaling pathway, and protect the integrity of colon tissue, thereby having a novel role in prevention or treatment therapy for UC. This work for the first time indicated that NA might be a potential functional food ingredient for preventing and treating inflammatory bowel disease (IBD).

Field application of cost-effective sensors for the monitoring of NH3, H2S, and TVOC in environmental treatment facilities and the estimation of odor intensity.

Odor is usually a complex mixture of various compounds. In many countries, odor complaints have been addressed using the air dilution olfactory method (ADOM) to reduce their malodor complaint. In this study, continuous monitoring of ammonia, hydrogen sulfide, and total volatile organic compounds (TVOC) using sensors was conducted in facilities for municipal and livestock wastewater treatment (LWT), and for food waste composting (FWC). Odor intensity was modeled by multivariate linear regression using sensor monitoring data with air dilution measured by the ADOM. In testing the performance of sensors in the lab, all three sensors showed acceptable values for linearity, accuracy, repeatability, lowest detection limit, and response time, so the sensors were acceptable for application in the field. In on-site real-time monitoring, the three sensors functioned well in the three environmental facilities during the testing period. Average ammonia and hydrogen sulfide concentrations were high in the LWT facility, while TVOC showed the highest concentration in the FWC facility. A longer sampling time is necessary for ammonia monitoring. Odor intensity from individual sensor data correlated well to complex odor measured by the ADOM. Finally, we suggest a protocol for field application of sensor monitoring and odor data reproduction.Implications: We suggest a protocol for the field application of sensor monitoring and odor data estimation in this study. This study can be useful to a policy maker and field operator to reduce odor emission through the determination of a more effective treatment technology and removal pathway for individual odorants.

Corrigendum: Clinical efficacy protocol of yinhuapinggan granules: A randomized, double-blind, parallel, and controlled clinical trial program for the intervention of community-acquired drug-resistant bacterial pneumonia as a complementary therapy.

[This corrects the article DOI: 10.3389/fphar.2022.852604.].

Clinical Efficacy Protocol of Yinhuapinggan Granules: A Randomized, Double-Blind, Parallel, and Controlled Clinical Trial Program for the Intervention of Community-Acquired Drug-Resistant Bacterial Pneumonia as a Complementary Therapy.

Background: Community-acquired bacterial pneumonia (CABP) is an important health care concern in the worldwide, and is associated with significant morbidity, mortality, and health care expenditure. Streptococcus pneumoniae is the most frequent causative pathogen of CABP. Common treatment for hospitalized patients with CABP is empiric antibiotic therapy using ß-lactams in combination with macrolides, respiratory fluoroquinolones, or tetracyclines. However, overuse of antibiotics has led to an increased incidence of drug-resistant S. pneumoniae, exacerbating the development of community-acquired drug-resistant bacterial pneumonia (CDBP) and providing a challenge for physicians to choose empirical antimicrobial therapy. Methods: Traditional Chinese medicine (TCM) is widely used as a complementary treatment for CDBP. Yinhuapinggan granules (YHPG) is widely used in the adjuvant treatment of CDBP. Experimental studies and small sample clinical trials have shown that YHPG can effectively reduce the symptoms of CDBP. However, there is a lack of high-quality clinical evidence for the role of YHPG as a complementary drug in the treatment of CDBP. Here, we designed a randomized, double-blind, placebo-controlled clinical trial to explore the efficacy and safety of YHPG. A total of 240 participants will be randomly assigned to the YHPG or placebo group in a 1:1 ratio. YHPG and placebo will be added to standard treatment for 10 days, followed by 56 days of follow-up. The primary outcome is the cure rate of pneumonia, and the secondary outcomes includes conversion rate of severe pneumonia, lower respiratory tract bacterial clearance, lactic acid (LC) clearance rate, temperature, C-reactive protein (CRP), criticality score (SMART-COP score), acute physiological and chronic health assessment system (APACHEII score) and clinical endpoint events. Adverse events will be monitored throughout the trial. Data will be analyzed according to a pre-defined statistical analysis plan. This research will disclose the efficacy of YHPG in acquired drug-resistant pneumonia. Clinical Trial Registration: https://clinicaltrials.gov, identifier ChiCTR2100047501.

Ganoderic acids-rich ethanol extract from Ganoderma lucidum protects against alcoholic liver injury and modulates intestinal microbiota in mice with excessive alcohol intake.

Alcoholic liver injury is mainly caused by excessive alcohol consumption and has become a global public health problem threatening human health. It is well known that Ganoderma lucidum possesses various excellent beneficial effects on liver function and lipid metabolism. The purpose of this study was to evaluate the underlying protective effect and action mechanism of ganoderic acids-rich G. lucidum ethanol extract (GLE) on alcohol-induced liver injury in mice with excessive alcohol intake. Results showed that oral administration of GLE could obviously inhibit the abnormal increases of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and also significantly protect the liver against alcohol-induced excessive hepatic lipid accumulation and pathological changes. In addition, alcohol-induced oxidative stress in liver was significantly ameliorated by the dietary intervention of GLE through reducing the hepatic levels of maleic dialdehyde (MDA) and lactate dehydrogenase (LDH), and increasing the hepatic levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and alcohol dehydrogenase (ADH). Compared with the model group, GLE intervention significantly ameliorated the intestinal microbial disorder by elevating the relative abundance of Ruminiclostridium_9, Prevotellaceae_UCG-001, Oscillibacter, [Eubacterium]_xylanophilum_group, norank_f_Clostridiates_vadinBB60_group, GCA-900066225, Bilophila, Ruminococcaceae_UCG-009, norank_f_Desulfovibrionaceae and Hydrogenoanaerobacterium, but decreasing the proportion of Clostridium_sensu_stricto_1. Furthermore, liver metabolomic profiling suggested that GLE intervention had a significant regulatory effect on the composition of liver metabolites in mice with excessive alcohol intake, especially the levels of some biomarkers involved in primary bile acid biosynthesis, riboflavin metabolism, tryptophan metabolism, biosynthesis of unsaturated fatty acids, fructose and mannose metabolism, glycolysis/gluconeogenesis. Additionally, dietary supplementation with GLE significantly regulated the mRNA levels of key genes related to fatty acids metabolism, ethanol catabolism and inflammatory response in liver. Conclusively, these findings indicate that GLE has a potentially beneficial effect on alleviating alcohol-induced liver injury and may be developed as a promising functional food ingredient.

Litchi chinensis seed prevents obesity and modulates the gut microbiota and mycobiota compositions in high-fat diet-induced obese zebrafish.

Obesity continues to be a global public health challenge. Litchi chinensis seed is rich in bioactive ingredients with pharmacological effects, such as hypoglycemic activity and anti-oxidation. This study aimed to assess the potential anti-obesity effects of L. chinensis seed and the changes of gut microbiota and mycobiota compositions in obese zebrafish induced by a high-fat diet. The anti-obesity effects were supplemented and validated in high-fat diet-induced obese mice. In this study, various chemical components of L. chinensis seed water and ethanol extracts were detected using UHPLC-QE-MS, and both extracts showed strong in vitro antioxidant activities. Network pharmacology analysis showed the potential of the extracts to improve obesity. Litchi chinensis seed powder, water and ethanol extracts decreased the weight of obese zebrafish, improved lipid accumulation and lipid metabolism, regulated appetite, and inhibited cell apoptosis and inflammation of the liver and intestine. They showed similar effects in obese mice, and also reduced the weight of fat tissues, regulated insulin resistance and glucose metabolism, and improved the intestinal barrier. Additionally, L. chinensis seed modulated the compositions of gut microbiota and mycobiota in zebrafish, with the regulation of the proportion of bacteria that produce short-chain fatty acids or affect intestine health, including Cetobacterium, Trichococcus, Aeromonas, Staphylococcus, and Micrococcaceae, and the proportion of fungi that produce mycotoxins or have special metabolic capacities, including Penicillium, Candida, Rhodotorula, and Trichoderma. Spearman's correlation analysis revealed the potential link between zebrafish obesity parameters, gut bacteria and fungi. Overall, these findings indicated that L. chinensis seed effectively improved obesity.

Dissociated Role of Thalamic and Cortical Input to the Lateral Amygdala for Consolidation of Long-Term Fear Memory.

Post-encoding coordinated reactivation of memory traces distributed throughout interconnected brain regions is thought to be critical for consolidation of memories. However, little is known about the role of neural circuit pathways during post-learning periods for consolidation of memories. To investigate this question, we optogenetically silenced the inputs from both auditory cortex and thalamus in the lateral amygdala (LA) for 15 min immediately following auditory fear conditioning (FC) and examined its effect on fear memory formation in mice of both sexes. Optogenetic inhibition of both inputs disrupted long-term fear memory formation tested 24 h after FC. This effect was specific such that the same inhibition did not affect short-term memory and context-dependent memory. Moreover, long-term memory was intact if the inputs were inhibited at much later time points after FC (3 h or 1 d after FC), indicating that optical inhibition for 15 min itself does not produce any nonspecific deleterious effect on fear memory retrieval. Selective inhibition of thalamic input was sufficient to impair consolidation of auditory fear memory. In contrast, selective inhibition of cortical input disrupted remote fear memory without affecting recent memory. These results reveal a dissociated role of thalamic and cortical input to the LA during early post-learning periods for consolidation of long-term fear memory.SIGNIFICANCE STATEMENT Coordinated communications between brain regions are thought to be essential during post-learning periods for consolidation of memories. However, the role of specific neural circuit pathways in this process has been scarcely explored. Using a precise optogenetic inhibition of auditory input pathways, either thalamic or cortical or both, to the LA during post-training periods, we here show that thalamic input is required for consolidation of both recent and remote fear memory, whereas cortical input is crucial for consolidation of remote fear memory. These results reveal a dissociated role of auditory input pathways to the LA for consolidation of long-term fear memory.

Physciosporin suppresses mitochondrial respiration, aerobic glycolysis, and tumorigenesis in breast cancer.

BACKGROUND: Physciosporin (PHY) is one of the potent anticancer lichen compound. Recently, PHY was shown to suppress colorectal cancer cell proliferation, motility, and tumorigenesis through novel mechanisms of action. PURPOSE: We investigated the effects of PHY on energy metabolism and tumorigenicity of the human breast cancer (BC) cells MCF-7 (estrogen and progesterone positive BC) and MDA-MB-231 (triple negative BC). METHODS: The anticancer effect of PHY on cell viability, motility, cancer metabolism and tumorigenicity was evaluated by MTT assay, migration assay, clonogenic assay, anchorage-independent colony formation assay, glycolytic and mitochondrial metabolism analysis, qRT-PCR, flow cytometric analysis, Western blotting, immunohistochemistry in vitro; and by tumorigenicity study with orthotopic breast cancer xenograft model in vivo. RESULTS: PHY markedly inhibited BC cell viability. Cell-cycle profiling and Annexin V-FITC/PI double staining showed that a toxic dosage of PHY triggered apoptosis in BC cell lines by regulating the B-cell lymphoma-2 (Bcl-2) family proteins and the activity of caspase pathway. At non-toxic concentrations, PHY potently decreased migration, proliferation, and tumorigenesis of BC cells in vitro. Metabolic studies revealed that PHY treatment significantly reduced the bioenergetic profile by decreasing respiration, ATP production, and glycolysis capacity. In addition, PHY significantly altered the levels of mitochondrial (PGC-1α) and glycolysis (GLUT1, HK2 and PKM2) markers, and downregulated transcriptional regulators involved in cancer cell metabolism, including ß-catenin, c-Myc, HIF-1α, and NF-κB. An orthotopic implantation mouse model of BC confirmed that PHY treatment suppressed BC growth in vivo and target genes were consistently suppressed in tumor specimens. CONCLUSION: The findings from our in vitro as well as in vivo studies exhibit that PHY suppresses energy metabolism as well as tumorigenesis in BC. Especially, PHY represents a promising therapeutic effect against hormone-insensitive BC (triple negative) by targeting energy metabolism.

Deciphering the Q-markers of nourishing kidney-yin of Cortex Phellodendri amurense from ZhibaiDihuang pill based on Chinmedomics strategy.

BACKGROUND: Cortex Phellodendri amurensis (CPA) has high medicinal value in the treatment of kidney-yin deficiency diseases. However, due to the lack of research on the therapeutic material basis of CPA, the current quality control standard for CPA is defective, and the effect of the nourishing kidney-yin of CPA was limited. PURPOSE: Based on the principle of correspondence between the syndrome and prescriptions, we studied the CPA in ZhibaiDihuang pill (ZBDH) to identify quality markers (Q-markers) of CPA in ZBDH for treating kidney-yin deficiency and seek the potential Q-markers of CPA under nourishing kidney-yin effect combined with the analysis of single CPA. METHODS: Taking Chinmedomics as the core strategy, metabonomics analysis and effective component identification were performed by UPLC-MS. RESULTS: A total of 121 chemical components of ZBDH were identified, among which the contents of berberine, palmatine, jatrorrhizine and magnoflorine changed the most obviously with the addition of CPA. Forty-five components were identified in the blood in the markedly effective state, including berberine, palmatine, jatrorrhizine and magnoflorine. The therapeutic material basis of ZBDH in the treatment of kidney-yin deficiency was found, and 6 components were found to derive from CPA, including magnoflorine and jatrorrhizine. In addition, seventeen components were identified in the blood in the single CPA treatment, including berberine, palmatine, jatrorrhizine and magnoflorine. CONCLUSIONS: Magnoflorine and jatrorrhizine were the Q-markers of CPA for treating kidney-yin deficiency in the formula of ZBDH and they were also potential Q-markers of the nourishing kidney-yin of CPA.

The Effects of Mindfulness-Based Mandala Coloring, Made in Nature, on Chronic Widespread Musculoskeletal Pain: Randomized Trial.

This study aimed to investigate the effects of mindfulness-based mandala coloring made within nature on individuals with chronic widespread musculoskeletal pain (CWP). Thirty-six participants were randomly allocated. In the experimental group, identical interventions and procedures were administered for each experiment. The control group members were untreated and remained in an urban environment. Overall, the experiment showed significant improvements in tender points (f = 8.791, p = 0.006), total stress level (f = 14.570, p = 0.001), depressive symptoms (f = 15.205, p = 0.001), anger symptoms (f = 7.263, p = 0.011) and salivary cortisol (f = 10.619, p = 0.003) in the experimental group. The results reflect that MBMC within nature is effective in reducing pain, psychological stress responses, and cortisol levels in individuals with CWP. The positive results could be a product of the experimental design rather than the treatment itself. A rigorous experimental design provides better understanding of MBMC within nature.

Effect of Red Ginseng Oil on Cultured Sebocytes and Outer Root Sheath Cells after Treatment with Lipopolysaccharide.

BACKGROUND: Ginseng has been known in Korea as a health-supportive herbal medicine from time immemorial. Essential oil isolated from fresh ginseng has been shown to display antibacterial and anti-inflammatory activities. OBJECTIVE: The effects of red ginseng oil (RGO) on the lipopolysaccharide (LPS)-treated sebocytes and outer root sheath (ORS) cells were studied. METHODS: The cultured cells were treated with either 0.1% dimethyl sulfoxide, 5 µg/ml LPS, 50 µg/ml RGO, or 5 µg/ml LPS plus 50 µg/ml RGO for 6 and 24 hours. RT-PCR, real-time PCR, enzyme-linked immunosorbent assay, western blot, and immunofluorescence staining were performed for the analysis of inflammatory cytokine. RESULTS: RGO showed the increased gene and protein expression of inflammatory cytokines, including interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α in the LPS-treated sebocytes and ORS cells. RGO also showed the increased protein expression of p-c-jun and p-JNK in the LPS-treated sebocytes and ORS cells. Gene expression of TLR2 was increased in LPS-treated sebocytes following treatment with RGO. Additionally, RGO resulted in an increased expression of LL-37 in the LPS-treated sebocytes and ORS cells. Moreover, it remarkably increased the production of sebum in LPS-treated sebocytes. CONCLUSION: RGO might be among the aggravating factors of acne vulgaris. It would be better to stop taking red ginseng in patients with inflammatory acne.

The Development and Operation of a Home Management System during the COVID-19 Pandemic: Experience of the Local Government Gyeonggi-do in Korea.

During the three the coronavirus disease 2019 (COVID-19) surges in South Korea, there was a shortage of hospital beds for COVID-19 patients, and as a result, there were cases of death while waiting for hospitalization. To minimize the risk of death and to allow those confirmed with COVID-19 to safely wait for hospitalization at home, the local government of Gyeonggi-do in South Korea developed a novel home management system (HMS). The HMS team, comprised of doctors and nurses, was organized to operate HMS. HMS provided a two-way channel for the taskforce and patients to monitor the severity of patient's condition and to provide healthcare counseling as needed. In addition, the HMS team cooperated with a triage/bed assignment team to expedite the response in case of an emergency, and managed a database of severity for real-time monitoring of patients. The HMS became operational for the first time in August 2020, initially managing only 181 patients; it currently manages a total of 3,707 patients. The HMS supplemented the government's COVID-19 confirmed case management framework by managing patients waiting at home for hospitalization due to lack of hospital and residential treatment center beds. HMS also could contribute a sense of psychological stability in patients and prevented the situation from worsening by efficient management of hospital beds and reduction of workloads on public healthcare centers. To stabilize and improve the management of COVID-19 confirmed cases, governments should organically develop self-treatment and HMS, and implement a decisive division of roles within the local governments.

Effect of Early High-Dose Vitamin D3 Repletion on Cognitive Outcomes in Critically Ill Adults.

BACKGROUND: Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. RESEARCH QUESTION: Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function? STUDY DESIGN AND METHODS: This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group. RESULTS: Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42). INTERPRETATION: In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov.

Majonoside-R2 extracted from Vietnamese ginseng protects H9C2 cells against hypoxia/reoxygenation injury via modulating mitochondrial function and biogenesis.

Vietnamese ginseng has a therapeutic effect on various diseases; however its bioactivity against cardiac hypoxia/reoxygenation (HR) injury remains unclear. In this study, we evaluated the protective roles of total saponin extract (TSE) and majonoside-R2 (MR2) targeting mitochondria in HR-induced rat cardiomyocyte H9C2 cells. The results showed that both TSE and MR2 effectively protected the cells from HR damage. Particularly, 9 µM of MR2 significantly increased the viability of HR-induced cells (p < 0.05). Interestingly, MR2 treatment markedly prevented the loss of mitochondrial membrane potential and cardiolipin content, and an increase in reactive oxygen species production in HR-treated H9C2 cells. Moreover, MR2 treatment altered the mRNA expression of genes involved in mitochondrial biogenesis under HR conditions. The present study documented for the first time the cardioprotective effects of MR2 against HR injury by maintaining mitochondrial function and modulating mitochondrial biogenesis.

The Toxicity and Attenuation Methods of Toxic Chinese Materia Medica for its Reasonable Application: A Review.

Over a millennia, traditional Chinese medicine (TCM) has been used to treat various diseases in China. In recent years, more and more Chinese materia medica (CMM) have been studied in scientific research projects, applied in clinical practice, and their extracts have even appeared in some health products. However, the toxicity of some CMM is often overlooked, including hepatotoxicity, nephrotoxicity, neurotoxicity, cardiotoxicity, etc. In this review, the toxic components and their toxicological mechanisms of some toxic CMM were listed according to the chemical structure classification of toxic components. Afterwards, the traditional methods (processing and compatibility) and modern methods (structural modification, biotransformation, etc.) of attenuation of CMM were discussed. Since ancient times, it has been said that "fight fire with fire, fight poison with poison," and toxic CMM are of great significance in the treatment of difficult and severe diseases. The rational application of toxic CMM and their components in clinical practice was also exemplified in this review. While the pharmacological effects of TCMs have been emphasized, the scientific attenuation and rational application of toxic components should be concerned. We hope this review can provide a reference for future related research.