Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

Synergistic neuroprotective effects of two natural medicinal plants against CORT-induced nerve cell injury by correcting neurotransmitter deficits and inflammation imbalance.

BACKGROUND: Lilium henryi Baker (Liliaceae) and Rehmannia glutinosa (Gaertn.) DC. (Plantaginaceae) were the traditional natural medicinal plants for the treatment of depression, but the antidepression mechanism of two plants co-decoction (Also known as Lily bulb and Rehmannia decoction (LBRD) drug-containing serum (LBRDDS) has not been elucidated in the in vitro model of depression. MATERIAL AND METHODS: Here, UHPLC-Q-TOF/MS was used to identify the active components of LBRDDS and the potential effector substance was identified by bioinformatics analysis. CORT-induced nerve cells cytotoxicity was used to investigate the neuroprotection effect of LBRDDS and the underlying pharmacological mechanisms were explored by multiple experimental methods such as molecular docking, immunofluorescence, gain- or loss-of function experiments. RESULTS: Bioactive compounds in LBRDDS absorbed from intestinal tract were transformed or metabolized by the gut microbiota including palmitic acid, adrenic acid, linoleic acid, arachidonic acid and docosapentaenoic acid. Network pharmacology analysis and molecular docking of showed fatty acid metabolism, neurotransmitter synthesis and neuroinflammation may be potential therapeutic targets of LBRDDS. LBRDDS can improve the activity of model cells, reduce cytotoxicity of lactate dehydrogenase, recover neurotransmitter imbalance, relieve inflammatory damage, down-regulate the expression of miRNA-144-3p, increase the mRNAs and protein expression level of Gad-67 and VGAT, and promote the synthesis and transport of GABA. CONCLUSION: Therefore, LBRDDS exerts neuroprotective effects by correcting neurotransmitter deficits and inflammation imbalance in the CORT-induced nerve cell injury model.

Verbascoside: A neuroprotective phenylethanoid glycosides with anti-depressive properties.

BACKGROUND: Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative and antineoplastic actions, and a wide range of therapeutic effects against depression. PURPOSE: In this review, we appraised preclinical and limited clinical evidence to fully discuss the anti-depression capacity of verbascoside and its holistic characteristics that can contribute to better management of depression in vivo and in vitro models, as well as, its toxicities and medicinal value. METHODS: This review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic review of 32 preclinical trials published up to April 2023, combined with a comprehensive bioinformatics analysis of network pharmacology and molecular docking, was conducted to elucidate the antidepressant mechanism of action of verbascoside. Studies included in the systematic review were obtained from 7 electronic databases: PubMed, Scopus, Web of Science, Cochrane, ResearchGate, ScienceDirect, and Google Scholar. RESULTS: Studies on the antidepressant effects of verbascoside showed that various pharmacological mechanisms and pathways, such as modulating the levels of monoamine neurotransmitters, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperfunction and promoting neuroprotection may be involved in the process of its action against depression. Verbascoside promotes dopamine (DA) biosynthesis by promoting the expression of tyrosine hydroxylase mRNA and protein, upregulates the expression of 5-hydroxytryptamine receptor 1B (5-HT1B), prominence protein, microtubule-associated protein 2 (MAP2), hemeoxygenase-1 (HO-1), SQSTM1, Recombinant Autophagy Related Protein 5 (ATG5) and Beclin-1, and decreases the expression of caspase-3 and a-synuclein, thus exerting antidepressant effects. We identified seven targets (CCL2, FOS, GABARAPL1, CA9, TYR, CA12, and SQSTM1) and three signaling pathways (glutathione metabolism, metabolism of xenobiotics by cytochrome P450, fluid shear stress and atherosclerosis) as potential molecular biological sites for verbascoside. CONCLUSIONS: These findings provide strong evidence that verbascoside exerts its antidepressant effects through various pharmacological mechanisms. However, further multicentre clinical case-control and molecularly targeted fishing studies are required to confirm the clinical efficacy of verbascoside and its underlying direct targets.

Effect of vitamin D3 supplementation in winter on physical performance of university students: a one-month randomized controlled trial.

BACKGROUND: There is epidemiological evidence which suggests an association between 25-hydroxyvitamin D [25(OH)D] levels and bone and muscle function; however, it is unclear whether vitamin D supplementation has an added benefit beyond bone health. Here, we investigated the effects of vitamin D3 supplementation (1 month) on physical performance in Chinese university students in winter. METHODS: One hundred and seventeen eligible subjects with 25(OH)D (19.2 ± 7.8 ng/mL) were randomly assigned to either vitamin D3 supplement (N = 56; 1000 IU/day) or the control (N = 61) group for 1 month. Pre- and post-measurements included: 1) serum levels of 25(OH)D; 2) musculoskeletal and pulmonary function [vertical jump height (VJH) and right handgrip strength (RHS), forced vital capacity (FVC), and forced expiratory volume at 1s (FEV1)]; 3) bone turnover markers [parathyroid hormone (PTH), n-terminal osteocalcin (N-MID), and calcium]; 4) hemoglobin-related parameters [hemoglobin (Hb), hematocrit (HCT), red blood cells (RBC), and red cell distribution width (RDW)]; 5) lipid parameters [total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)]; 6) Fatigue-related indicators [serum creatine kinase (CK), lactate dehydrogenase (LDH), and total testosterone (T)]. In addition, aerobic capacity was assessed by measuring maximal oxygen uptake (VO2max) at baseline. RESULTS: During wintertime, supplementation with 1000 IU/d of vitamin D3 significantly increased serum 25(OH)D levels (from 18.85 ± 7.04 to 26.98 ± 5.88 ng/mL, p < 0.05), accompanied by a decrease of PTH (p < 0.05). However, vitamin D3 supplementation did not significantly impact the physical performance, serum lipid parameters, and bone turnover markers of students. Furthermore, 25(OH)D was found to be positively correlated with VJH and negatively correlated with PTH and TC at the beginning and end of the study (p < 0.05). In addition, the multiple linear regression analysis showed that 25(OH)D combined with athletic, gender, height, weight, Hb, and FVC could account for 84.0% of the VO2max value. CONCLUSIONS: The study demonstrated that one-month of 1000 IU/d of vitamin D3 supplementation during the winter had beneficial effects on 25(OH)D status and PTH. However, vitamin D3 intervention was not sufficient to improve physical performance. Furthermore, 25(OH)D levels combined with athletic, Hb and FVC could be a predictor of VO2max.

AR/PCC herb pair inhibits osteoblast pyroptosis to alleviate diabetes-related osteoporosis by activating Nrf2/Keap1 pathway.

Osteoporosis is a prevalent complication of diabetes, characterized by systemic metabolic impairment of bone mass and microarchitecture, particularly in the spine. Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been extensively employed in Traditional Chinese Medicine to manage diabetes; however, its potential to ameliorate diabetic osteoporosis (DOP) has remained obscure. Herein, we explored the protective efficacy of AR/PCC herb pair against DOP using a streptozotocin (STZ)-induced rat diabetic model. Our data showed that AR/PCC could effectively reduce the elevated fasting blood glucose and reverse the osteoporotic phenotype of diabetic rats, resulting in significant improvements in vertebral trabecular area percentage, trabecular thickness and trabecular number, while reducing trabecular separation. Specifically, AR/PCC herb pair improved impaired osteogenesis, nerve ingrowth and angiogenesis. More importantly, it could mitigate the aberrant activation of osteoblast pyroptosis in the vertebral bodies of diabetic rats by reducing increased expressions of Nlrp3, Asc, Caspase1, Gsdmd and IL-1ß. Mechanistically, AR/PCC activated antioxidant pathway through the upregulation of the antioxidant response protein Nrf2, while concurrently decreasing its negative feedback regulator Keap1. Collectively, our in vivo findings demonstrate that AR/PCC can inhibit osteoblast pyroptosis and alleviate STZ-induced rat DOP, suggesting its potential as a therapeutic agent for mitigating DOP.

Traditional Chinese medicine invigorating the spleen and kidney promotes HBsAg seroclearance in the mouse model.

Traditional Chinese medicine (TCM) is often used as an adjuvant or alternative therapy for abnormal liver biochemistry or liver fibrosis associated with chronic hepatitis B (CHB). However, the role of TCM in HBsAg seroclearance remains unclear. We aimed at exploring the role and possible mechanisms of TCM in HBsAg seroclearance. Fifteen widely used TCM granules invigorating the spleen and kidneys were screened. C57BL/6J mice were administered daily with TCM granules by gavage for 1 week. The effect of TCM on the M1 polarization of macrophages was measured using a CD86 assay. According to the principles of formulating prescriptions, three single TCM with the most noticeable effect on M1 polarization, accompanied by two other TCM granules, were used to develop a TCM formula. The hepatitis B virus-expressing mouse model was constructed by hydrodynamic injection of the pAAV/HBV1.2 plasmid. Hepatitis B virus-expressing mice were gavaged daily with phosphate-buffered saline (PBS), TCM formula, or Codonopsis Radix, for 1 week. HBsAg, HBeAg, and hepatitis B virus DNA levels were measured. In addition, gut microbiota was profiled using 16S rDNA sequencing. Several TCM granules showed significant effects on M1 polarization. The TCM formula accelerated HBsAg seroclearance compared with the Codonopsis Radix and PBS groups. Intrahepatic M1 polarization, as indicated by flow cytometry and immunohistochemistry, was induced in the TCM formula and Codonopsis Radix groups. The abundance of Alloprevotella significantly increased in the TCM formula and Codonopsis Radix groups. These results demonstrate that the TCM formula for invigorating the spleen and kidney can accelerate HBsAg seroclearance. This effect can be attributed, at least in part, to M1 polarization of intrahepatic macrophages.

Efficacy and safety of acupuncture for post-COVID-19 depression: a protocol for systematic review and meta-analysis.

INTRODUCTION: Post-COVID-19 depression (PCD) is a possible sequela of COVID-19. Some doctors have used acupuncture to treat PCD, but no systematic review or meta-analysis has yet evaluated its efficacy and safety for the treatment of PCD. The aim of this systematic review is to assess the efficacy and safety of acupuncture therapy for PCD. METHODS AND ANALYSIS: Two reviewers will independently search the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (PubMed), Excerpt Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP) and Wan-Fang Database from inception to 24 January 2023. Study selection, data extraction and assessment of study quality will be independently performed by two reviewers. If a meta-analysis is appropriate, Review Manager V.5.3 will be used for data synthesis; otherwise, a descriptive analysis will be conducted. Data will be synthesised using a fixed-effects or random-effects model, according to the results of a heterogeneity test. The results will be presented as risk ratios with 95% CIs for dichotomous data, and weighted mean differences or standardised mean differences with 95% CIs for continuous data. ETHICS AND DISSEMINATION: The entire process used for this systematic review does not use private information, so ethical approval is not required. The results of this meta-analysis will be disseminated through publication in a peer-reviewed journal and/or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022379312.

Mechanism of lily bulb and Rehmannia decoction in the treatment of lipopolysaccharide-induced depression-like rats based on metabolomics study and network pharmacology.

CONTEXT: Lily bulb and Rehmannia decoction (LBRD), consisting of Lilium henryi Baker (Liliaceae) and Rehmannia glutinosa (Gaertn) DC (Plantaginaceae), is a specialized traditional Chinese medicine formula for treating depression. However, the underlying mechanisms, especially the relationship between LBRD efficacy and metabolomics, remains unclear. OBJECTIVE: This study was aimed to investigate the metabolic mechanism of LBRD in treating depression. MATERIALS AND METHODS: Network pharmacology was conducted using SwissTargetPrediction, DisGeNET, DrugBank, Metascape, etc., to construct component-target-pathway networks. The depression-like model was induced by intraperitoneal injection with lipopolysaccharide (LPS) (0.3 mg/kg) for 14 consecutive days. After the administration of LBRD (90 g/kg) and fluoxetine (2 mg/kg) for 14 days, we assessed behaviour and the levels of neurotransmitter, inflammatory cytokine and circulating stress hormone. Prefrontal metabolites of rats were detected by using liquid chromatography-mass spectrometry metabolomics method. RESULTS: The results of network pharmacology showed that LBRD mainly acted on neurotransmitter and second messenger pathways. Compared to the model group, LBRD significantly ameliorated depressive phenotypes and increased the level of 5-HT (13.4%) and GABA (24.8%), as well as decreased IL-1ß (30.7%), IL-6 (32.8%) and TNF-α (26.6%). Followed by LBRD treatment, the main metabolites in prefrontal tissue were contributed to retrograde endocannabinoid signalling, glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, autophagy signal pathway, etc. DISCUSSION AND CONCLUSIONS: LBRD were effective at increasing neurotransmitter, attenuating proinflammatory cytokine and regulating glycerophospholipid metabolism and glutamatergic synapse, thereby ameliorating depressive phenotypes. This research will offer reference for elucidating the metabolomic mechanism underlying novel antidepressant agents contained LBRD formula.

[Mechanism of Qingwei Powder in treatment of periodontitis based on UPLC-Q-TOF-MS, GC-MS, network pharmacology and molecular docking].

The present study explored the mechanism of Qingwei Powder(QP) in the treatment of periodontitis based on chromatography-mass spectrometry and network pharmacology-molecular docking techniques. UPLC-Q-TOF-MS and GC-MS were used to identify the chemical constituents of QP. The active components and targets were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and their targets were predicted using SwissTargetPrediction. Targets related to periodontitis were obtained from GeneCards, OMIM, and DisGeNET. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. Cytoscape 3.7.2 was used to construct the "chemical component-target-disease" network. The targets were analyzed for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by clusterProfiler R, and the "chemical component-target-pathway" network was constructed. The binding activity of the active components to the target proteins was verified by molecular docking. A total of 189 chemical components were obtained by UPLC-Q-TOF-MS and GC-MS, including 39 active components with 180 potential targets related to periodontitis. Target enrichment analysis of the active components yielded 92 KEGG pathways. Twenty KEGG pathways, 34 active components, and 99 targets were involved in the "chemical component-target-pathway" network. Molecular docking verified a good binding ability of the key targets to the key compounds. This study preliminarily indicates that QP is effective in treating periodontitis through multiple components, multiple targets, and multiple pathways, which reflects the complex system of Chinese medicine. This study provides the theoretical foundation for the subsequent research on the material basis and key quality attributes of QP.

Deep Learning-Based Universal Expert-Level Recognizing Pathological Images of Hepatocellular Carcinoma and Beyond.

Background and Aims: We aim to develop a diagnostic tool for pathological-image classification using transfer learning that can be applied to diverse tumor types. Methods: Microscopic images of liver tissue with and without hepatocellular carcinoma (HCC) were used to train and validate the classification framework based on a convolutional neural network. To evaluate the universal classification performance of the artificial intelligence (AI) framework, histological images from colorectal tissue and the breast were collected. Images for the training and validation sets were obtained from the Xiamen Hospital of Traditional Chinese Medicine, and those for the test set were collected from Zhongshan Hospital Xiamen University. The accuracy, sensitivity, and specificity values for the proposed framework were reported and compared with those of human image interpretation. Results: In the human-machine comparisons, the sensitivity, and specificity for the AI algorithm were 98.0, and 99.0%, whereas for the human experts, the sensitivity ranged between 86.0 and 97.0%, while the specificity ranged between 91.0 and 100%. Based on transfer learning, the accuracies of the AI framework in classifying colorectal carcinoma and breast invasive ductal carcinoma were 96.8 and 96.0%, respectively. Conclusion: The performance of the proposed AI framework in classifying histological images with HCC was comparable to the classification performance achieved by human experts, indicating that extending the proposed AI's application to diagnoses and treatment recommendations is a promising area for future investigation.

Baihe Dihuang (Lilium Henryi Baker and Rehmannia Glutinosa) decoction attenuates somatostatin interneurons deficits in prefrontal cortex of depression via miRNA-144-3p mediated GABA synthesis and release.

ETHNOPHARMACOLOGICAL RELEVANCE: Baihe Dihuang Decoction is a well-known traditional Chinese medicine prescription (Also known as Lilium Henryi Baker and Rehmannia Glutinosa Decoction, LBRD) composed of Lilium Henryi Baker bulb and raw juice from Rehmannia Glutinosa (Gaertn) DC with the curative efficacy of nourishing yin and clearing heat based on the Chinese herbal medicine theory. It has been used as routine medication in treating depression combined with conventional western medicine in China for years. AIM OF THE STUDY: LBRD can attenuates GABAergic deficits in the medial prefrontal cortex (mPFC) of depression. This study aimed to investigate the mechanism of antidepressive properties of LBRD in the prefrontal GABAergic interneuron subtypes, including parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP)-positive neuron. MATERIALS AND METHODS: In this project, chronic unpredicted mild stress paradigm was adopted to construct depression model. After treated with LBRD standard decoction and behaviors test, the level of GABA associated miRNA/mRNA and GABAergic subtype-specific markers were detected by qRT-PCR and Western blot. The lncRNAs/miRNAs/GABA regulatory axis was verified by luciferase reporter assay, RNA immunoprecipitation, RNA pull-down assay, and theses changes were measured in LBRD administration with the use of immunofluorescence staining and RNA-fluorescence in situ hybridization. RESULTS: In the current study, we found that LBRD exhibited high efficacy based on the results of behavioral tests. Meanwhile, LBRD also improved the reduced GABA levels in depression by increasing the expression of lncRNA Neat1 and Malat1, as well as decreasing miRNA-144-3p and miRNA-15b-5p. Moreover, the level of Sst mRNA and protein that were harvested from the mPFC tissues of depression group was significantly lower than those in the control mice. While, these changes can be reverted by LBRD standard decoction administration. Whereas, neither chronic stress nor treatment can change the level of PV and VIP mRNAs and protein expression. In the SST-positive neuron of mPFC tissues, treatment with LBRD standard decoction resulted in the elevation of Gad-67, VGAT, GAT-3 and a reduction of miRNA-144-3p expression. CONCLUSIONS: These findings suggested that LBRD antidepressant activities may be related to ameliorating the SST-positive neuron deficits via regulating the miRNA-144-3p mediated GABA synthesis and release.

[Quality value transmitting of substance benchmarks in Danggui Buxue Decoction].

To clarify the key quality attributes of substance benchmarks in Danggui Buxue Decoction(DBD), this study prepared 21 batches of DBD substance benchmarks, and established two methods for detecting their fingerprints, followed by the identification of peak attribution and similarity range as well as the determination of extract and transfer rate ranges and contents of index components ferulic acid, calycosin-7-O-ß-D-glucoside, and astragaloside Ⅳ. The mass fractions and transfer rates of DBD substance benchmarks from different batches were calculated as follows: ferulic acid(index component in Angelicae Sinensis Radix): 0.037%-0.084% and 31.41%-98.88%; astragaloside Ⅳ(index component in Astragali Radix): 0.021%-0.059% and 32.18%-118.57%; calycosin-7-O-ß-D-glucoside: 0.002%-0.023% and 11.51%-45.65%, with the extract rate being 18.4%-36.1%. The similarity of fingerprints among 21 batches of DBD substance benchmarks was all higher than 0.9. The quality control method for DBD substance benchmarks was preliminarily established based on the HPLC fingerprint analysis and index component determination, which has provided a basis for the subsequent development of DBD and the quality control of novel related preparations.

Integrated analysis of the chemical-material basis and molecular mechanisms for the classic herbal formula of Lily Bulb and Rehmannia Decoction in alleviating depression.

BACKGROUND: Lily Bulb and Rehmannia Decoction (LBRD), is a traditional Chinese formula that has been shown to be safe and effective against depression; however, its material basis and pharmacological mechanisms remain unknown. METHODS: Here, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) and high-performance liquid chromatography (HPLC) were used to identify the chemical spectrum and qualitatively identify the major active ingredients in the LBRD standard decoction, respectively. Subsequently, we assessed the behavior, neuronal function and morphology, neurotransmitter levels, hypothalamic-pituitary-adrenal (HPA)-axis associated hormones, inflammatory cytokine levels, and miRNA/mRNA expression alterations in an in vitro/vivo depression model treated by the LBRD standard decoction. Finally, miRNA/mRNA regulatory networks were created through bioinformatics analysis, followed by functional experiments to verify its role in LBRD standard decoction treatment. RESULTS: A total of 32 prototype compounds were identified in the LBRD standard decoction, and the average quality of verbascoside in the fresh lily bulb decoction, fresh raw Rehmannia juice, and the LBRD standard decoction were 0.001264%, 0.002767%, and 0.009046% (w/w), respectively. Administration of the LBRD standard decoction ameliorated chronic unpredictable mild stress (CUMS)-induced depression-like phenotypes and protected PC12 cells against chronic corticosterone (CORT)-induced injury. The levels of neurotransmitter, cytokine, stress hormones and neuronal morphology were disrupted in the depression model, while LBRD standard decoction could work on these alterations. After LBRD standard decoction administration, four differentially expressed miRNAs, rno-miR-144-3p, rno-miR-495, rno-miR-34c-5p, and rno-miR-24-3p, and six differentially expressed mRNAs, Calml4, Ntrk2, VGAT, Gad1, Nr1d1, and Bdnf overlapped in the in vivo/vitro depression model. Among them, miR-144-3p directly mediated GABA synthesis and release by targeting Gad1 and VGAT, and miR-495 negatively regulated BDNF expression. The LBRD standard decoction can reverse the above miRNA/mRNA network-mediated GABA and BDNF expression in the in vivo/vitro depression model. CONCLUSION: Collectively, the multi-components of the LBRD standard decoction altered a series of miRNAs in depression through mediating GABAergic synapse, circadian rhythm, and neurotrophic signaling pathway etc., thereby abolishing inhibitory/excitatory neurotransmitter deficits, recovering the pro-/anti-inflammatory cytokine levels and regulating the HPA-axis hormone secretion to achieve balance of the physiological function of the whole body.

Gender differences in Damp-Heat Syndrome: A review.

Gender differences have important biological significance for medical research. In this study, a bias towards males was identified in animal experiments of Damp-Heat Syndrome in traditional Chinese medicine, as was first proposed by a data mining method. Combined with the correlation between Damp-Heat Syndrome in traditional Chinese medicine and Gender differences, it was considered that Gender-related factors have a significant influence on the development of Damp-Heat Syndrome in traditional Chinese medicine. However, most traditional Chinese medicine studies ignore the key significance of Gender-related factors. This study emphasises that the development of modern traditional Chinese medicine research needs to pay full attention to the biological significance of Gender-related factors and to apply this concept to the research on the Gender equivalence strategy in basic research and the practice of personalised medical diagnosis and clinical treatment.

Arsenate toxicity to the marine microalga Chlorella vulgaris increases under phosphorus-limited condition.

To understand the arsenic (As) toxicity to aquatic organisms in the phosphors-polluted aquatic ecosystem, the growth, the physiological response of Chlorella vulgaris exposed to As (V), and the underlying mechanism were investigated under different phosphorus (P) levels (0, 6, 13, 32 µM). Results showed that As toxicity to the marine microalga C. vulgaris was enhanced under P-limited condition. P supply distinctly altered the effect of As on the light-harvesting efficiency of photosystem. Insufficient P supply also resulted in an enhanced level of membrane integrity loss, which probably facilitated As entering cells and led to stronger toxicity to C. vulgaris under low P supply. At high concentrations of As, the relative superoxide dismutase (SOD) activity was significantly enhanced. When phosphorus was limited, the activation of peroxidase (POD) was significantly enhanced after adding As (V). When intracellular SOD activity was at its highest level, the level of membrane peroxidation (MDA) was also at the highest level, and membrane peroxidation level was positively related to the level of membrane integrity loss (Pearson R2=0.8977). These results suggested that alternation of light-harvesting efficiency of photosystem and As-induced oxidative damage, resulting in membrane peroxidation and integrity loss, were the possible mechanism of As toxicity to C. vulgaris. This study provided insight into the understanding of As toxicity to algae in the eutrophication aquatic system and the potential application of algae in As remediation.

[Application of "process management and evaluation" in resident standardization training plan in acupuncture-moxibustion department of hospital for postgraduates of non-acupuncture- moxibustion speciality].

The teaching effect of "process management and evaluation" was assessed in resident standardization training plan in acupuncture-moxibustion department of hospital for postgraduates of non-acupuncture-moxibustion speciality. A total of 120 postgraduates of non-acupuncture-moxibustion speciality participating in resident standardization training were randomized into an observation group (60 cases) and a control group (60 cases, 1 case dropped off). In the control group, the conventional training mode was used. In the observation group, the "process management and evaluation" was adopted, in which, the syllabus was refined, various teaching modes were cooperated and the summary was conducted once a week. The training results were evaluated at the end of 1-month shift test and questionnaire was issued in all of the postgraduates of the two groups. In the observation group, the score for theory and the score of each of the items for technical ability, named differentiation and treatment, technical manipulation and physician-patient communication, as well as the total score were all higher than the control group successively (P<0.05, P<0.01). The results of the student questionnaire showed that in the items as "being liable to the memory of relevant knowledge" "connection of theory with practical ability" "stimulating students' interest and subjective initiative" "self-learning ability" "clinical question handling ability" and "communication ability with patients" as well as the total score in the observation group were all higher than the control group successively (P<0.01, P<0.05). The teaching effect of "process management and evaluation" is obviously better than the conventional teaching mode.

Lack of Myosin X Enhances Osteoclastogenesis and Increases Cell Surface Unc5b in Osteoclast-Lineage Cells.

Normal bone mass is maintained by balanced bone formation and resorption. Myosin X (Myo10), an unconventional "myosin tail homology 4-band 4.1, ezrin, radixin, moesin" (MyTH4-FERM) domain containing myosin, is implicated in regulating osteoclast (OC) adhesion, podosome positioning, and differentiation in vitro. However, evidence is lacking for Myo10 in vivo function. Here we show that mice with Myo10 loss of function, Myo10m/m , exhibit osteoporotic deficits, which are likely due to the increased OC genesis and bone resorption because bone formation is unchanged. Similar deficits are detected in OC-selective Myo10 conditional knockout (cko) mice, indicating a cell autonomous function of Myo10. Further mechanistic studies suggest that Unc-5 Netrin receptor B (Unc5b) protein levels, in particular its cell surface level, are higher in the mutant OCs, but lower in RAW264.7 cells or HEK293 cells expressing Myo10. Suppressing Unc5b expression in bone marrow macrophages (BMMs) from Myo10m/m mice by infection with lentivirus of Unc5b shRNA markedly impaired RANKL-induced OC genesis. Netrin-1, a ligand of Unc5b, increased RANKL-induced OC formation in BMMs from both wild-type and Myo10m/m mice. Taken together, these results suggest that Myo10 plays a negative role in OC formation, likely by inhibiting Unc5b cell-surface targeting, and suppressing Netrin-1 promoted OC genesis. © 2019 American Society for Bone and Mineral Research.

[Nasal resorption of prim-O-glucosylcimifugin and 5-O-methylvisammioside in rats].

In this experiment, rat nasal mucosa absorption characteristics of prim-O-glucosylcimifugin and 5-O-methylvisammioside were studied to provide a basis for drug delivery of Toutongning nasal spray. The nasal mucosa absorption test in rats was conducted with in situ nasal perfusion method after pH 6 buffer solution was used to prepare high, medium and low concentrations of prim-O-glucosylcimifugin, 5-O-methylvisammioside mixed solution as liquid circulation in nasal cavity. Then the concentrations of the circulating liquid compositions to be measured were determined by HPLC, and the absorption rates of prim-O-glucosylcimifugin and 5-O-methylvisammioside under different pH conditions were also investigated. According to the results, the absorption rate constant was (0.588±0.041)×10⁻³, (0.547±0.023)×10⁻³, (0.592±0.063)×10⁻³ min⁻¹ for prim-O-glucosylcimifugin high, middle and low concentrations, and (0.438±0.041)×10⁻³, (0.407±0.023)×10⁻³, and (0.412±0.063)×10⁻³ min⁻¹ for 5-O-methylvisammioside high, middle and low concentrations. There was no significant difference among high, middle and low concentration groups, and the absorption under pH 6 was better than that under other pH conditions. Therefore, we can get the conclusion that the main active ingredient of Toutongning nasal sprays can be absorbed through the nasal mucosa, and it is feasible to make nasal spray; in addition, pH 6 of nasal spray is scientific and reasonable.

[Screen absorption enhancer for intranasal administration preparations of paeoniflorin based on nasal perfusion method in rats].

This experiment was aimed to screen the absorption enhancer for intranasal administration preparations of paeoniflorin. In this study, HPLC method for determination of paeoniflorin in perfusion liquid was established and the improved model of nasal perfusion in rats was used to screen out the species and amounts of absorption enhancer. In order to avoid the influence of the secretion and absorption of nasal cavity on the volume of perfusion fluid, the residual dose was calculated by using the volume correction method. Linear regression was carried out between the logarithm to the percentage of the residual dose and the corresponding time, and the slope of the regression line was exactly the absorption rate constant. Experimental results showed that hydroxypropyl-ß-cyclodextrin and water-soluble azone can significantly improve the nasal absorption of paeoniflorin. Furthermore, water-soluble azone had the highest absorption rate constant and the best promoting penetration effect on intranasal administration preparations of paeoniflorin. It was also found that when the mass concentration of water-soluble azone in the perfusion liquid increased from 5 g•L⁻¹ to 20 g•L⁻¹, the absorption rate constant was gradually increased and peaked at 20 g•L⁻¹. When the mass concentration was increased to 30 g•L⁻¹, the absorption rate constant was decreased, indicating that the best mass concentration of water-soluble azone was 20 g•L⁻¹.

[Research on Biological Assessment for Panax notoginseng Quality on Real-time Cell Electronic Analysis].

OBJECTIVE: To establish the quality control and evaluation methods of Panax notoginseng on promoting blood circulation and removing blood stasis effects, by determining cell index to evaluate the quality of Panax notoginseng from different habitats. METHODS: Using the real-time cell electronic analysis technology (RTCA) to examine the biological activity of specific cell-dependent cell lines on Panax notoginseng extracts. Changing trends and laws of the samples within a certain time were analyzed, and the cell index at the optimum time was determined. RESULTS: In four batches of Panax notoginseng from different habitats, cell index of Panax notoginseng from Chuxiong of Yunnan Province at the optimal time of 38 h was the highest, and the biological activity was the strongest. Cell index of Panax notoginseng from Wenshan of Yunnan Province at the optimal time of 38 h cells was the lowest, and the biological activity was the weakest. CONCLUSION: The method based on the real-time cell electronic analysis technology can initially be used in the detection of biological activity of Panax notoginseng.