Cohort profile: Using primary care data to understand Opioid Prescribing, Policy Impacts and Clinical Outcomes (OPPICO) in Victoria, Australia.

PURPOSE: The OPPICO cohort is a population-based cohort based on non-identifiable electronic health records routinely collected from 464 general practices in Victoria, Australia, created with the aim of understanding opioid prescribing, policy impacts and clinical outcomes. The aim of this paper is to provide a profile of the study cohort by summarising available demographic, clinical and prescribing characteristics. PARTICIPANTS: The cohort described in this paper comprises people who were aged at least 14 years at cohort entry, and who were prescribed an opioid analgesic at least once at participating practices for a total of 1 137 728 person-years from 1 January 2015 to 31 December 2020. The cohort was formed using the data collected from electronic health records through the Population Level Analysis and Reporting (POLAR) system. The POLAR data primarily consist of patient demographics, clinical measurements, Australian Medicare Benefits Scheme item numbers, diagnoses, pathology testing and prescribed medications. FINDING TO DATE: In total, the cohort consists of 676 970 participants with 4 389 185 opioid prescription records from 1 January 2015 to 31 December 2020. Approximately half (48.7%) received a single opioid prescription, and 0.9% received more than 100 opioid prescriptions. The mean number of opioid prescriptions per patient was 6.5 (SD=20.9); prescriptions for strong opioids accounted for 55.6% of all opioid prescriptions. FUTURE PLANS: The OPPICO cohort data will be used for various types of pharmacoepidemiological research, including examining the impact of policy changes on coprescription of opioids with benzodiazepines and gabapentin, and monitoring trends and patterns of other medication utilisation. Through data-linkage between our OPPICO cohort and hospital outcome data, we will examine whether policy changes for opioid prescribing lead to changes in prescription opioid-related harms, and other drug and mental health-related outcomes. TRIAL REGISTRATION NUMBER: EU PAS Register (EUPAS43218, prospectively registered).

[Excretion of three alkaloids from Simiao Pills in urine, feces, and bile between normal and type 2 diabetic rats].

This study investigated the differences in excretion kinetics of three alkaloids and their four metabolites from Simiao Pills in normal and type 2 diabetic rats. The diabetes model was established in rats by injection of streptozotocin, and the alkaloids in urine, feces, and bile of normal and diabetic rats were detected by LC-MS/MS to explore the effect of diabetes on alkaloid excretion of Simiao Pills. The results showed that 72 h after intragastric administration of the extract of Simiao Pills, feces were the main excretion route of alkaloids from Simiao Pills. The total excretion rates of magnoflorine and berberine in normal rats were 4.87% and 56.54%, which decreased to 2.35% and 35.53% in diabetic rats, which had statistical significance(P<0.05). The total excretion rates of phellodendrine, magnoflorine, and berberine in the urine of diabetic rats decreased significantly, which were 53.57%, 60.84%, and 52.78% of those in normal rats, respectively. After 12 h of intragastric administration, the excretion rate of berberine in the bile of diabetic rats increased significantly, which was 253.33% of that of normal rats. In the condition of diabetes, the excretion rate of berberine metabolite, thalifendine significantly decreased in urine and feces, but significantly increased in bile. The total excretion rates of jateorrhizine and palmatine in the urine increased significantly, and t_(1/2) and K_e changed significantly. The results showed that diabetes affected the in vivo process of alkaloids from Simiao Pills, reducing their excretion in the form of prototype drug, affecting the biotransformation of berberine, and ultimately increasing the exposure of alkaloids in vivo, which would be conducive to the hypoglycemic effect of alkaloids. This study provides references for the clinical application and drug development of Simiao Pills in diabetes.

Network Pharmacology Integrated with Transcriptomics Analysis Reveals Ermiao Wan Alleviates Atopic Dermatitis via Suppressing MAPK and Activating the EGFR/AKT Signaling.

Background: Ermiao Wan (EMW) is commonly used to treat atopic dermatitis (AD) in China. However, the pharmacological mechanisms underlying the action of EMW against AD remain unclear. Purpose: We aimed to determine the mechanisms underlying the effectiveness of EMW in the treatment of AD. Methods: We evaluated the effect of EMW on AD induced by dinitrochlorobenzene (DNCB) in BALB/C mice. To clarify the key components of EMW in AD treatment, the main components of EMW were identified using HPLC. Serum pharmacochemistry was used to analyze the absorbed ingredients from blood. Based on the phytochemical results, network pharmacology and molecular docking were used to predict the action of EMW. Skin transcriptomic analysis was used to validate the network pharmacology results. RT-qPCR,ELISA, and immunohistochemical were performed to validate the results of skin transcriptomics. Results: EMW improved the symptoms of AD, with less rashes, less spontaneous scratching, less inflammatory cell infiltration, and fewer allergic reactions. The established HPLC method is simple and reliable. Chlorogenic acid, phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and atractylodin were the key effective ingredients with a high blood concentration. Fifty-seven primary causal targets of EMW against AD were identified. These targets are mainly involved in ErbB signaling pathways including EGFR, AKT1, MAPK8, JUN, MAPK1. Molecular docking showed that EGFR, AKT1, MAPK8, JUN, MAPK1 had good binding force with EMW. In AD mice, EMW regulated the EGFR/AKT signaling through upregulation of Grb2, GAB1, Raf-1, EGFR, and AKT, and downregulation of MAPK1 and JUN, compared to that in the MD group. Conclusion: EMW could alleviate AD through activating EGFR/AKT signaling and suppressing MAPK. This study provides a theoretical basis for the clinical use of EMW.

Behavioral Training of High-Functioning Autistic Children by Music Education of Occupational Therapy.

Autistic children, also known as "children from the stars", have been discovered for more than half a century, but there is still no unified conclusion on the diagnosis, causes, manifestations, and education of autism. The current theory and practice suggest that there is a need to improve the treatment and education of these children. According to existing theories and practices, most autistic children show a special interest in music, and music is very effective in the treatment of autistic children, and through musical activities, children with autism can improve their language, social and emotional, cognitive, and sensorimotor development. In this paper, we record and observe the music classes of children with autism. We select two classes with a total of seven children with autism as the observation subjects in the music classes, record the changes in various aspects and behavioral performance of these seven children with autism in the music activities, and analyze and summarize them. The main purpose of this study is to analyze and summarize how the three major music teaching methods are implemented in the music classroom for autistic children and how they can help autistic children with different characteristics. In the end, we summarize the main problems of music teaching for autistic children found in practice and try to make some suggestions, hoping to provide reference for scholars who study music education for autistic children. The music teaching activities were effective in improving the children's joint attention, movement imitation, rhythm imitation, and cooperation ability, and all three children improved to varying degrees, fulfilling the goals of the teaching activities. The behavioral analysis of the three children during the teaching activities showed that the three children improved their ability to sit comfortably, awareness, musical ability, and rule awareness and reduced inappropriate behaviors and bad emotions, which proved that music education could improve the social and cognitive skills of the children.

Gegen Qinlian decoction restores the intestinal barrier in bacterial diarrhea piglets by promoting Lactobacillus growth and inhibiting the TLR2/MyD88/NF-κB pathway.

Acute bacterial diarrhea is a severe global problem with a particularly high incidence rate in children. The microecology inhabiting the intestinal mucosa is the key factor leading to diarrhea. Gegen Qinlian decoction (GQD) is used to treat bacterial diarrhea, however, its underlying mechanism remains unclear. Thus, this study aimed to clarify the restorative effect of GQD on the intestinal barrier from the perspective of gut microbiota. A Tibetan piglet model with bacterial diarrhea was established through orally administered Escherichia coli, and diarrheal piglets were treated with GQD for three days. After treatment, GQD significantly ameliorated the diarrheal symptoms. GQD decreased the levels of IL-6, LPS, and DAO, and increased SIgA, ZO-1, and occludin levels in intestinal mucosa, indicating the restoration of intestinal barrier. GQD modulated the microbial compositions inhabited on the intestinal mucosa, especially an increase of the Lactobacillus. Spearman analysis showed that Lactobacillus was the key genus of intestinal barrier-related bacteria. Bacterial culture in vitro validated that GQD directly promoted Lactobacillus growth and inhibited E. coli proliferation. Moreover, the expressions of TLR2, MyD88, and NF-κB in the colon decreased after GQD treatment. In conclusion, GQD may treat diarrhea and restore the intestinal mucosal barrier by facilitating Lactobacillus growth and inhibiting the TLR2/MyD88/NF-κB signaling pathway.

Nutrition, Bioactive Components, and Hepatoprotective Activity of Fruit Vinegar Produced from Ningxia Wolfberry.

Wolfberry (Lycium barbarum L.) is a nutritious and medicinal fruit, and deeply processed products of wolfberry needs to be improved. In this study, nutrition, bioactive compounds, and hepaprotective activity were explored in wolfberry vinegar (WFV). The contents of nutrients including total sugar and protein in WFV samples were 2.46 and 0.27 g/100 mL, respectively. Total phenolic and flavonoid contents in WFV were 2.42 mg GAE/mL and 1.67 mg RE/mL, respectively. p-Hydroxybenzoic acid and m-hydroxycinnamic acid were the main polyphenols in WFV. The antioxidant activity of WFV were 20.176 mM Trolox/L (ABTS), 8.614 mM Trolox/L (FRAP), and 26.736 mM Trolox/L (DPPH), respectively. In addition, WFV treatment effectively alleviated liver injury by improving histopathological changes and reducing liver biochemical indexes in CCl4-treated mice. WFV alleviated oxidative damage by inhibiting oxidative levels and increasing antioxidant levels. These results suggest that WFV can be utilized as a functional food to prevent oxidative liver injury.

Rediscovery of Traditional Plant Medicine: An Underestimated Anticancer Drug of Chelerythrine.

In many studies, the extensive and significant anticancer activity of chelerythrine (CHE) was identified, which is the primary natural active compound in four traditional botanical drugs and can be applied as a promising treatment in various solid tumors. So this review aimed to summarize the anticancer capacities and the antitumor mechanism of CHE. The literature searches revolving around CHE have been carried out on PubMed, Web of Science, ScienceDirect, and MEDLINE databases. Increasing evidence indicates that CHE, as a benzophenanthridine alkaloid, exhibits its excellent anticancer activity as CHE can intervene in tumor progression and inhibit tumor growth in multiple ways, such as induction of cancer cell apoptosis, cell cycle arrest, prevention of tumor invasion and metastasis, autophagy-mediated cell death, bind selectively to telomeric G-quadruplex and strongly inhibit the telomerase activity through G-quadruplex stabilization, reactive oxygen species (ROS), mitogen-activated protein kinase (MAPK), and PKC. The role of CHE against diverse types of cancers has been investigated in many studies and has been identified as the main antitumor drug candidate in drug discovery programs. The current complex data suggest the potential value in clinical application and the future direction of CHE as a therapeutic drug in cancer. Furthermore, the limitations and the present problems are also highlighted in this review. Despite the unclearly delineated molecular targets of CHE, extensive research in this area provided continuously fresh data exploitable in the clinic while addressing the present requirement for further studies such as toxicological studies, combination medication, and the development of novel chemical methods or biomaterials to extend the effects of CHE or the development of its derivatives and analogs, contributing to the effective transformation of this underestimated anticancer drug into clinical practice. We believe that this review can provide support for the clinical application of a new anticancer drug in the future.

The anti-diabetic activity of polyphenols-rich vinegar extract in mice via regulating gut microbiota and liver inflammation.

Polyphenols in vinegar are benefit to human health. The purpose of this research was to identify the polyphenols-rich vinegar extract (VE) and evaluate the anti-diabetic mechanisms in vivo. The results showed that 29 polyphenols were identified by UPLC-Q/Trap-MS/MS analysis. 4-Hydroxybenzoic acid, ferulic acid, and ethyl ferulate were the main polyphenols. In addition, VE relieved the symptoms of type 2 diabetes mellitus (T2DM) by down-regulating blood glucose and lipemia. VE reduced inflammation by inhibiting TLR4/NF-κB signaling pathway. Furthermore, VE treatment restored gut microbiota dysbiosis (upregulating Bacteroidetes, Lactobacillus, Bifidobacterium, and Bacteroides and downregulating Firmicutes, Proteobacteria, and Enterorhabdus abundances), and increased short chain fatty acids contents in diabetic mice, which participated in anti-diabetic effect of VE by correlation analysis. These findings suggest that VE may be a candidate for T2DM intervention by regulating gut microbiota and inflammation.

Near-infrared spectroscopy and machine learning-based technique to predict quality-related parameters in instant tea.

The traditional method for analyzing the content of instant tea has disadvantages such as complicated operation and being time-consuming. In this study, a method for the rapid determination of instant tea components by near-infrared (NIR) spectroscopy was established and optimized. The NIR spectra of 118 instant tea samples were used to evaluate the modeling and prediction performance of a combination of binary particle swarm optimization (BPSO) with support vector regression (SVR), BPSO with partial least squares (PLS), and SVR and PLS without BPSO. Under optimal conditions, Rp for moisture, caffeine, tea polyphenols, and tea polysaccharides were 0.9678, 0.9757, 0.7569, and 0.8185, respectively. The values of SEP were less than 0.9302, and absolute values of Bias were less than 0.3667. These findings indicate that machine learning can be used to optimize the detection model of instant tea components based on NIR methods to improve prediction accuracy.

Assessment of clinical competency among TCM medical students using standardized patients of traditional Chinese medicine: A 5-year prospective randomized study.

BACKGROUND: Some Western medicine schools in China established standardized patient (SP) programs for medical education. However, SP programs are rarely applied to the education of traditional Chinese medicine (TCM). In this study, we evaluated the effectiveness of using standardized patient traditional Chinese medicine (SP-TCM) to improve clinical competency among TCM medical students. METHODS: This study was a prospective, 2-group, parallel-training randomized trial over the course of 5 years. Data were collected from September 2016 to December 2020. Participants in each year were randomly allocated into the traditional-method training group or the SP-TCM training group (1:1) for a 3-month curriculum. Measurement of clinical competency among all trainees was based on a standardized examination composed of scores of medical record documentation, scores of TCM syndrome differentiation and therapeutic regimen, and checklist assessment from both SP-TCMs and TCM professionals. Feedback was collected using semi-constructive questionnaires from both groups. RESULTS: Compared with those assigned to traditional-method training, those assigned to SP-TCM training demonstrated significantly greater post-training improvement in medical record documentation and TCM syndrome differentiation and therapeutic regimen. Moreover, SP-TCM trainees outscored those assigned to traditional training in the assessment for encounter performance given by independent SP-TCMs and TCM professionals. The SP-TCM method gained higher satisfaction of training efficacy and test performance than the traditional method. CONCLUSION: This SP-TCM program demonstrated great benefits for improving clinical competency among TCM medical students.

Comparative pharmacokinetics, intestinal absorption and urinary excretion of six alkaloids from herb pair Phellodendri Chinensis cortex-Atractylodis Rhizoma.

Phellodendri Chinensis Cortex (PCC) and Atractylodis Rhizoma (AR) are frequently used as herb pair to treat eczema and gout owing to their synergistic effects. Alkaloids are the major ingredients from PCC and the effect of their combination on the in vivo processing of alkaloids remains unclear. In this study, a simple and reliable UPLC-MS/MS method for simultaneous determination of six alkaloids in rat plasma was developed. This method was applied to a comparative pharmacokinetic study between PCC and PCC-AR in rats. Effect of AR on absorption of alkaloids was investigated by a single-pass intestinal perfusion study. The effect of AR on urinary excretion of alkaloids was studied. Pharmacokinetic studies showed that the values of rea under the concentration-time curve of phellodendrine, magnoflorine and palmatine were greater in the PCC-AR group than in the PCC group. The intestinal absorptive parameters absorption rate constant and effective permeability of phellodendrine and jatrorrhizine in PCC-AR groups were higher than those in the PCC group. Urinary excretion studies revealed that the excreted amount of alkaloids in the PCC-AR group was lower than that in the PCC group. The results revealed that the combination of PCC and AR improves intestinal absorption of alkaloids and reduces their urinary excretion, which enhances their systemic exposure. This study may explain the synergetic effects of PCC and AR in clinical applications.

Simiao Wan and its ingredients alleviate type 2 diabetes mellitus via IRS1/AKT2/FOXO1/GLUT2 signaling.

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease. Simiao Wan (SMW) is a commonly used clinical drug for hyperuricemia treatment. SMW has been confirmed to improve insulin resistance and is expected to be a novel hypoglycemic agent. However, the hypoglycemic bioactive ingredients and mechanisms of action of SMW are unclear. Objective: To explore the hypoglycemic effects and reveal the mechanisms of SMW and bioactive ingredients (SMW-BI). Study design and methods: The hypoglycemic effects of SMW and SMW-BI were verified in a mouse model of T2DM induced by streptozotocin (STZ) and a high-fat and high-sugar diet (HFSD). Network pharmacology was used to predict the mechanisms of SMW and SMW-BI. Histological analysis and real-time quantitative polymerase chain reaction (RT-qPCR) verified network pharmacology results. RT-qPCR results were further verified by immunofluorescence (IFC) and molecular docking. The correlation between proteins and biochemical indicators was analyzed by Spearman's correlation. Results: Chlorogenic acid, phellodendrine, magnoflorine, jateorhizine, palmatine, berberine, and atractydin were identified as SMW-BI. After 8 weeks of treatment, SMW and SMW-BI decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-C), increased the level of high-density lipoprotein cholesterol (HDL-C), alleviated weight loss, and increased serum insulin levels in T2DM mice. In addition, SMW and SMW-BI improved hepatocyte morphology in T2DM mice, decreased the number of adipocytes, and increased liver glycogen. Network pharmacological analysis indicated that SMW and SMW-BI may exert hypoglycemic by regulating insulin receptor substrate 1 (IRS1)/RAC-beta serine/threonine-protein kinase (AKT2)/forkhead box protein O1 (FOXO1)/glucose transporter type 2 (GLUT2) signaling. Moreover, correlation analysis showed that SMW and SMW-BI were associated with activation of IRS1, AKT2, and GLUT2, and inhibiting FOXO1. RT-qPCR revealed that SMW and SMW-BI could increase levels of IRS1, AKT2, and GLUT2 in the livers of T2DM mice and lower the level of FOXO1. Furthermore, immunofluorescence analysis showed that FOXO1 expression in the livers of T2DM mice decreased after oral administration of SMW and SMW-BI. Furthermore, molecular docking showed that SMW-BI could bind directly to IRS1 and AKT2. Conclusion: SMW and SMW-BI are potential hypoglycemic drugs that alleviate T2DM by regulating IRS1/AKT2/FOXO1 signaling. Our study provides a research idea for screening the bioactive ingredients in traditional Chinese medicine (TCM).

Coix seed polysaccharides alleviate type 2 diabetes mellitus via gut microbiota-derived short-chain fatty acids activation of IGF1/PI3K/AKT signaling.

Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years. Coix seed (CS) as a homologous substance of traditional Chinese medicine and food, its polysaccharides can improve the symptoms of patients with metabolic disorders. Since most plant polysaccharides are difficult to digest and absorb, we hypothesized that Coix seed polysaccharides (CSP) exert hypoglycemic effects through the gut. In this study, the underlying mechanisms regulating hypoglycemic effects of CSP on a T2DM mouse model were investigated. After treatment with CSP, serum insulin and high-density lipoprotein cholesterol levels were increased, while total cholesterol, triglycerides and low-density lipoprotein cholesterol levels were decreased in T2DM mice. In addition, CSP treatment helped repair the intestinal barrier and modulated the gut microbial composition in T2DM mice, mainly facilitating the growth of short-chain fatty acid (SCFA)-producing bacteria, Spearman's analysis revealed these bacteria were positively related with the hypoglycemic efficacy of CSP. Colonic transcriptome analysis indicated the hypoglycemic effect of CSP was associated with the activation of the IGF1/PI3K/AKT signaling pathway. Correlative analysis revealed that this activation may result from the increase of SCFAs-producing bacteria by CSP. GC-MS detection verified that CSP treatment increased fecal SCFAs levels. Molecular docking revealed that SCFAs could bind with IGF1, PI3K, and AKT. Our findings demonstrated that CSP treatment modulates gut microbial composition, especially of the SCFAs-producing bacteria, activates the IGF1/PI3K/AKT signaling pathways, and exhibits hypoglycemic efficacy.

[Comparative analysis of pharmacokinetics and intestinal absorption of six alkaloids between Sanmiao Pills and Simiao Pills in rats].

The present study investigated the differences in pharmacokinetics and intestinal absorption of six alkaloids in Sanmiao Pills and Simiao Pills in rats and explored the different efficacies of the two formulae. After oral administration of Sanmiao Pills and Simiao Pills in rats, blood samples were collected at different time points. Samples were prepared for the determination of six alkaloids in plasma by UPLC-MS/MS. The chromatography was performed on an ACE Excel 3 C_(18 )column with acetonitrile-0.1% formic acid in water as the mobile phase for gradient elution. Analytes were detected in the positive ion mode. Plasma concentrations and pharmacokinetic parameters were calculated. Intestinal absorption of alkaloids was investigated by single-pass intestinal perfusion and absorption parameters of ingredients were calculated. The results showed that the UPLC-MS/MS method for simultaneous determination of concentrations of six alkaloids in plasma was developed and validated by methodological investigations, such as specificity, calibration curves, precision, accuracy, recovery, matrix effect, and stability. The results of the pharmacokinetic assay revealed that C_(max) and AUC values of phellodendrine, berberine, magnoflorine, berberrubine, and jatrorrhizine in Simiao Pills were significantly increased, and CL/F values were reduced as compared with those in Sanmiao Pills, which indicated the increase in plasma concentrations of alkaloids. The intestinal absorption parameters K_(a )and P_(eff) values of phellodendrine, berberine, and jatrorrhizine in Simiao Pills were higher than those in Sanmiao Pills. The intestinal absorption and plasma concentrations of alkaloids in Simiao Pills were significantly higher than those in Sanmiao Pills, suggesting that the composition of Simiao Pills was more conducive to the alkaloids into the blood to resist inflammation and lower uric acid.

A novel therapy for granulomatous lobular mastitis: Local heat therapy.

Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast condition that is characterized by granulomatous inflammation. GLM remains a refractory disease due to its failure to respond to routine anti-inflammatory therapies and its high recurrence rate. Thus, the present study aimed to investigate the application of local heat therapy in GLM as a potential therapeutic strategy. The results revealed that the application of local heat therapy was associated with a shortened remission time for GLM, while the remission and recurrence rates were similar to those of existing therapies. The median first remission time following local heat therapy was significantly decreased compared with that following corticosteroid therapy (5.30 months vs. 11.27 months; P<0.05). The remission rates were not significantly different between the local heat therapy (76.9%), extensive excision (90.4%) and the corticosteroid therapy (85.7%) groups (P>0.05). In addition, the recurrence rates were not statistically different between the groups (local heat therapy, 8.3%; extensive excision, 10%; and corticosteroid therapy, 10%; P>0.05). The local heat therapy showed mild adverse effects and shortened healing times compared to the other therapies; however, further confirmation is required.

Brachybacterium subflavum sp. nov., a novel actinobacterium isolated from the foregut of grass carp.

A novel actinobacterium, designated CFH 10395T, was isolated from the foregut of grass carp (Ctenopharyngodon idella), which had been fed with ginseng extract supplement. The taxonomic position was investigated by a polyphasic approach. Cells of CFH 10395T were Gram-staining-positive, aerobic, ovoid-shaped, non-spore-forming and non-motile. On the basis of the results of 16S rRNA gene sequence analysis, CFH 10395T was most closely related to Brachybacterium endophyticum KCTC 49087T, Brachybacterium squillarum JCM 16464T and Brachybacterium paraconglomeratum JCM 17781T (97.85%, 97.51 and 97.29% similarity, respectively). CFH 10395T grew at 4-37 °C, pH 5.0-9.0 and in the presence of up to 10.0 % NaCl (w/v). The dominant menaquinone was MK-7. The whole-cell sugars were rhamnose, glucose, mannose and galactose. meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The genome size was 3.99 Mbp with a DNA G+C content of 71.9 mol%. On the basis of the results of phylogenetic analysis, physiological properties, chemotaxonomic characteristics, low average nucleotide identity (ANI) and digital DDH (dDDH) results [ANI calculated using MUMmer (ANIm) <87 %, ANI calculated using blast (ANIb) <83 % and dDDH <23 %], it is concluded that CFH 10395T represents a novel species of the genus Brachybacterium, for which the name Brachybacterium subflavum sp. nov., is proposed. The type strain is CFH 10395T (=CGMCC 1.13804T=KCTC 49235T).

Higenamine alleviates allergic rhinitis by activating AKT1 and suppressing the EGFR/JAK2/c-JUN signaling.

BACKGROUND: Allergic rhinitis (AR) is an inflammatory, immunoglobulin E (IgE)-mediated disease characterized by the typical symptoms of sneezing, rhinorrhea, nasal itching, and congestion. Higenamine (HG) is a plant-based alkaloid, possesses a wide range of activities, including vascular and tracheal relaxation, antioxidative, antiapoptotic, anti-inflammatory, and immunomodulatory activities. So far, the effect and the underlying mechanism of HG on AR have not been studied. HYPOTHESIS/PURPOSE: The purpose of this study was to evaluate the effects of HG on AR and investigate its underlying mechanism. METHODS: The effects of HG on AR were evaluated in an ovalbumin-induced AR mouse model. Network pharmacology-based methods such as target prediction, protein-protein interaction (PPI) network analysis, pathway analysis, and molecular docking were used to identify the likely HG targets. Finally, we validated the mechanism of action of HG through its effects on these targets in human nasal epithelial cells (HNEpCs). RESULTS: Oral administration of 30, 60, and 120 mg/kg HG significantly alleviated rubbing and sneezing in AR mice and attenuated histopathological changes in the lung and nasal tissues. Additionally, HG reduced the levels of IgE, histamine, and IL-4 in the serum of AR mice, and regulated imbalance in Th1/Th2 cells. Using network pharmacology-based methods, we identified 29 HG targets related to AR. These targets are mainly involved in the PD-L1, relaxin, estrogen, HIF-1, Th1 and Th2 cell differentiation, T cell receptor, and the Th17 cell differentiation signaling pathways. Molecular docking showed that HG may well be suited to the receptor binding pockets of key target AKT1, EGFR, c-Jun, NOS2, and JAK2. In HNEpCs, HG inhibited the histamine-induced mRNA expression and secretion of interleukin (IL)-6, and IL-8, as well as the expression of MUC5AC and the phosphorylation of NF-κB. Moreover, HG affected the changes of AKT1, EGFR, c-Jun, iNOS, and JAK2 induced by histamine. CONCLUSION: Overall, our results suggest that HG may alleviate AR by activating AKT1 and suppressing the EGFR/JAK2/c-JUN signaling. HG, therefore, has great potential as a therapeutic agent for the treatment of AR.

Polyphenol-rich vinegar extract regulates intestinal microbiota and immunity and prevents alcohol-induced inflammation in mice.

Zhenjiang aromatic vinegar (ZAV), a traditional fermented food in China, is rich in polyphenols with health-beneficial effects. In this study, vinegar extract ameliorated ethanol-induced liver injury by reducing the levels of oxidative stress biomarkers. In addition, vinegar extract regulated gut microbiota composition and immune factors, and improved antimicrobial peptides (Reg3b and Reg3g) and intestinal homeostasis in ethanol-treated mice. Vinegar extract suppressed lipopolysaccharide (LPS)-mediated inflammatory response in the liver and gut of ethanol-treated mice. Moreover, Akkermansia, Lachnospiraceae_NK4A136_group and Bacteroidetes showed a positive correlation with intestinal immune factors and antimicrobial peptides, and a negative correlation with parameters of oxidative stress and inflammation. In contrast, Firmicutes, Proteobacteria, Bilophila and Butyricimonas showed the opposite correlation with these parameters. Our study provides a new sight into vinegar extract for the prevention of ethanol-induced liver damage via modulation of gut-liver axis.

Formation mechanisms and characterisation of the typical polymers in melanoidins from vinegar, coffee and model experiments.

Melanoidins, are of increasing interest for their potential biological activities. However, little knowledge is available on their structure. In the present study, vinegar, coffee and model melanoidins were degraded by NaBH4, and the resultant reaction products were characterised by chromatography, mass spectrometry and spectrometry methods to elucidate the mechanism of formation of melanoidin skeleton molecules. The study identified a typical polymer with a molecular weight (MW) interval of 74 Da, which was polymerised by aldol condensation and reduced by NaBH4, followed by intermolecular dehydration. MW of the theoretically derived typical polymers matched the detected polymers, validating the speculated pathway involved in the formation of melanoidins skeleton molecules. The study also revealed that melanoidins from different sources contain polymers with the same MW and different binding preferences, contributing to the heterogeneity of melanoidins. Overall, these findings indicated that the identified polymers could be used as potential candidate biomarkers for melanoidins.

Efficacy of electroacupuncture for the treatment of asthenozoospermia: A protocol for systematic review and meta-analysis.

INTRODUCTION: Infertility has affected millions of couples aged 15 to 44 years worldwide. Recently, some studies suggest that abnormal semen quality is the main cause of male infertility and asthenozoospermia accounts for 19% of the infertility of men. The situation has brought a huge burden to the patient with asthenozoospermia and society. Acupuncture is a part of traditional Chinese medicine. Electroacupuncture (EA) has gained in popularity. Although a positive effect of manual acupuncture and EA on sperm parameters has been documented in several studies, there still a lack of more solid evidence. We hope to provide a convincing study for EA. METHODS AND ANALYSIS: The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Cochrane Library, Clinicaltrials. org, China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, Chinese Clinical Trial Registry will be retrieved. All the randomized controlled trials of rESWT for patients with CP/CPPS will be included. We will evaluate the outcomes including NIH-CPSI, VAS, IPSS, IIEF-5, and conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The present study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on October 31st, 2021. CONCLUSIONS: EA for asthenospermia is a microtrauma surgery with less pain. EA can effectively improve sperm motility; however, its efficacy has not been assessed scientifically and systematically. To address this limitation, this study will inspect the efficacy and safety of the EA in patients with asthenospermia. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences. PROTOCOL REGISTRATION NUMBER: INPLASY2020100071.