Spatial Visual Imagery (SVI)-Based Electroencephalograph Discrimination for Natural CAD Manipulation.

With the increasing demand for natural interactions, people have realized that an intuitive Computer-Aided Design (CAD) interaction mode can reduce the complexity of CAD operation and improve the design experience. Although interaction modes like gaze and gesture are compatible with some complex CAD manipulations, they still require people to express their design intentions physically. The brain contains design intentions implicitly and controls the corresponding body parts that execute the task. Therefore, building an end-to-end channel between the brain and computer as an auxiliary mode for CAD manipulation will allow people to send design intentions mentally and make their interaction more intuitive. This work focuses on the 1-D translation scene and studies a spatial visual imagery (SVI) paradigm to provide theoretical support for building an electroencephalograph (EEG)-based brain-computer interface (BCI) for CAD manipulation. Based on the analysis of three spatial EEG features related to SVI (e.g., common spatial patterns, cross-correlation, and coherence), a multi-feature fusion-based discrimination model was built for SVI. The average accuracy of the intent discrimination of 10 subjects was 86%, and the highest accuracy was 93%. The method proposed was verified to be feasible for discriminating the intentions of CAD object translation with good classification performance. This work further proves the potential of BCI in natural CAD manipulation.

Harmonizing international quality standards for Andrographis paniculata: A comparative analysis of content determination methods across pharmacopeias.

The quality standards for Andrographis paniculata, a widely used medicinal herb, exhibited significant variations across different pharmacopeias. In this study, we compared the HPLC content determination methods and total lactone content of A. paniculata samples from different regions, as specified in the Chinese (CP), United States (USP), European (EP), Thai (TP), and Indian pharmacopeias (IP), as well as the Hong Kong Chinese Materia Medica Standards (HK). We aimed to assess the differences and similarities among these pharmacopeias and harmonized international quality standards for A. paniculata. The analysis revealed variations in sample preparation, liquid chromatographic conditions, fingerprint profiles, and total lactone content among the different pharmacopeias. Specifically, the CP and HK methods exhibited superior sample preparation and chromatographic separation. Further comparing the content of 20 A. paniculata samples with the CP, USP, EP and HK methods showed consistent determinations for the same components, indicating similar detection capabilities. The discrepancies in total lactone content primarily stemmed from differences in the number and types of detected compounds. Moreover, the acceptance criteria exhibited a stringency in the order CP > HK > EP > USP. In conclusion, this comparison analysis of content determination in CP, USP, HK, EP, TP and IP provided a scientific foundation for the international standardization and trade regulations of A. paniculata. It also served as a valuable reference for the development of international quality standards for other medicinal herbs, facilitating the harmonization of global pharmaceutical standards.

Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease.

Introduction: Ganshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown. Methods: A mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology. Results: Ganshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan. Conclusion: Ganshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application.

Maackiain inhibits proliferation and promotes apoptosis of nasopharyngeal carcinoma cells by inhibiting the MAPK/Ras signaling pathway.

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.

Study of Xuanhuang Pill in protecting against alcohol liver disease using ultra-performance liquid chromatography/time-of-flight mass spectrometry and network pharmacology.

Introduction: Xuanhuang Pill (XHP) is a traditional Chinese medicine oral formula composed of 10 herbs. This study aims to verify the hepatoprotective activity of XHP and explain its possible mechanism. Methods: The hepatoprotective activity of XHP was evaluated by constructing a mouse model of alcoholic liver disease, and the mechanism of XHP was preliminarily explained by utilizing ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-QTOF/MS), proteomics and network pharmacology. Results: The current study demonstrated that treatment with XHP ameliorated acute alcohol-induced liver injury in mice by significantly reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and triglycerides (TGs) and malondialdehyde (MDA) content. Remarkably, treatment also increased superoxide dismutase (SOD) activity and glutathione (GSH) content. UPLC-QTOF/MS, 199 compounds were identified as within the make-up of the XHP. Network pharmacology analysis showed that 103 targets regulated by 163 chemical components may play an important role in the protective liver effect mediated by XHP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggest that the HIF-1, FoxO, PI3K-Akt, insulin, and thyroid hormone signaling pathways are key modulators of XHP's effects. Finally, eight key targets including Mapk1, Mapk3, Akt1, Map2k1, Pik3ca, Pik3cg, Raf1, and Prkca were verified by molecular docking and proteomics analysis, which provide insight into the hepatoprotective effect observed with XHP treatment. Conclusion: In summary, these results improved upon knowledge of the chemical composition and the potential mechanisms of hepatoprotective action of oral XHP treatment, providing foundational support for this formulation as a viable therapeutic option for alcoholic liver disease.

[Overview of research and development of polypeptide drugs and traditional Chinese medicine-peptides].

Peptide is a compound consisting of 2-50 amino acids, which is intermediate between small molecule and protein. It is characterized by a variety of biological activities, easy absorption, strong specific targeting, and few side effects and has become one of the hotspots in biomedical research in recent years. Chinese medicine contains a large number of peptides. The traditional processing methods such as decocting and boiling can effectively boost peptides to exert their due biological activities. At present, however, the research on Chinese medicinal components in laboratory generally employs high-concentration alcohol extraction method, which may cause the peptides to be ignored in many natural Chinese medicines. Substantial studies have revealed that the peptides in Chinese medicine are important material basis responsible for the traditional efficacy. Based on years of research and literature retrieval, this study put forward the concept of "traditional Chinese medicine(TCM)-peptides", referring to the components consisting of two or more amino acids with molecular weight between small molecules and proteins that can express the efficacy of Chinese medicine. Furthermore, this study also summarized the extraction and separation of TCM-peptides, and structure determination methods and routes, predicted the research prospect of modern research methods of TCM-peptides based on "holistic view" and big data. The artificial intelligence prediction was combined with high-throughput screening technology to improve the discovery efficiency and accuracy of TCM-peptides, and holographic images between TCM-peptides and biological targets were established to provide references for the innovative drug design and related health product development of TCM-peptides based on TCM theories.

Multicomponent Characterization of the Flower Bud of Panax notoginseng and Its Metabolites in Rat Plasma by Ultra-High Performance Liquid Chromatography/Ion Mobility Quadrupole Time-of-Flight Mass Spectrometry.

The flower bud of Panax notoginseng (PNF) consumed as a tonic shows potential in the prevention and treatment of cardiovascular diseases. To identify the contained multi-components and, in particular, to clarify which components can be absorbed and what metabolites are transformed, unveiling the effective substances of PNF is of vital significance. A unique ultrahigh-performance liquid chromatography/ion mobility quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) profiling approach and efficient data processing by the UNIFITM bioinformatics platform were employed to comprehensively identify the multi-components of PNF and the related metabolites in the plasma of rats after oral administration (at a dose of 3.6 g/kg). Two MS2 data acquisition modes operating in the negative electrospray ionization mode, involving high-definition MSE (HDMSE) and data-dependent acquisition (DDA), were utilized aimed to extend the coverage and simultaneously ensure the quality of the MS2 spectra. As a result, 219 components from PNF were identified or tentatively characterized, and 40 thereof could be absorbed. Moreover, 11 metabolites were characterized from the rat plasma. The metabolic pathways mainly included the phase I (deglycosylation and oxidation). To the best of our knowledge, this is the first report that systematically studies the in vivo metabolites of PNF, which can assist in better understanding its tonifying effects and benefit its further development.

AGI grade-guided chaiqin chengqi decoction treatment for predicted moderately severe and severe acute pancreatitis (CAP trial): study protocol of a randomised, double-blind, placebo-controlled, parallel-group, pragmatic clinical trial.

BACKGROUND: Acute pancreatitis (AP) is a common digestive disease with increased incidence globally but without internationally licenced pharmacological therapy. Moderately severe and severe acute pancreatitis (MSAP/SAP) contributes predominately for its morbidities and mortality and has been managed in West China Hospital for decades using the traditional Chinese medicinal formula chaiqin chengqi decoction (CQCQD). The current study tests whether the early administration of CQCQD will result in improved clinical outcomes in predicted MSAP/SAP patients. METHODS: This is a single-centre, randomised, controlled, double-blind pragmatic clinical trial. AP patients aged 18-75 admitted within 72 h of onset will be assessed at admission for enrolment. We excluded the predicted mild acute pancreatitis (Harmless Acute Pancreatitis Score > 2 at admission) and severe organ failure (Sequential Organ Failure Assessment [SOFA] score of respiratory, cardiovascular, or renal systems > 3) at admission. Eligible patients will be randomly allocated on a 1:1 basis to CQCQD or placebo control administration based on conventional therapy. The administration of CQCQD and placebo is guided by the Acute Gastrointestinal Injury grade-based algorithm. The primary outcome measure will be the duration of respiratory failure (SOFA score of respiratory system ≥ 2) within 28 days after onset. Secondary outcome measures include occurrence of new-onset any organ failure (SOFA score of respiratory, cardiovascular, or renal system ≥ 2) and new-onset persistent organ failure (organ failure lasts > 48 h), dynamic surrogate biochemical markers and clinical severity scores, gut-centred treatment modalities, local complications status, intensive care need and duration, surgical interventions, mortality, and length of hospital stay. Follow-up will be scheduled on 6, 12, and 26 weeks after enrolment to assess AP recurrence, local complications, the requirement for surgical interventions, all-cause mortality, and patient-reported outcomes. DISCUSSION: The results of this study will provide high-quality evidence to appraise the efficacy of CQCQD for the early management of AP patients. TRIAL REGISTRATION: Chictr.org.cn Registry ( ChiCTR2000034325 ). Registered on 2 July, 2020.

Structure of a new glycyrrhiza polysaccharide and its immunomodulatory activity.

A component of licorice polysaccharide (GPS-1) was extracted from licorice, its primary structure was identified and characterized for the first time, and its immunomodulatory activity was studied. Crude licorice polysaccharide was isolated and purified by DEAE sepharose FF ion-exchange column chromatography and Chromdex 200 PG gel filtration column chromatography to obtain a purified Glycyrrhiza polysaccharide named GPS-1. NMR and methylation analysis revealed that GPS-1 is composed of homogalacturonan (HG)-type pectin with 4)-D-GalpA-(1 as the backbone. This study of GPS-1 also examined its significant role in regulating immune activity in vitro and in vivo. As a result, GPS-1 promoted the secretion of IFN-γ and IL-4 in mice and increased the proportion of CD3+CD4+ and CD3+CD8+ T lymphocytes in their spleens. Dendritic cells (DCs) treated with GPS-1 showed promotion of DC maturation, antigen presentation, and phagocytic capacity. The results suggest that GPS-1 is a potential immunomodulator that stimulates the immune system by regulating multiple signaling pathways. Combined with our characterization of the primary structure of GPS-1, the present investigation provides the basis for future study of the form-function relationship of polysaccharides.

Study on the compatibility principle of Wutou Decoction based on network pharmacology / 数字中医药（英文）

@#Objective To investigate the underlying drug enhancement mechanisms of the Chuanwu (Aconiti Radix) and Huangqi (Astragali Radix) combination and toxicity reduction of Chuanwu combined with Gancao (Glycyrrhizae Radix et Rhizoma) in Wutou Decoction (乌头汤, WTD), and to elucidate the compatibility principle. Methods The active compounds and potential effective targets of the selected combinations were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicines Integrated Database (TCMID). The toxicity of Chuanwu (Aconiti Radix) was investigated by selecting all five toxic compounds from the literature and the TCMSP database, and obtaining their targets through SwissTargetPrediction. Targets related to rheumatoid arthritis (RA) were searched using DisGeNET, GenCards, and Online Mendelian Inheritance in Man (OMIM). Mutual targets between the drug pairs and RA were selected as potential RA therapy targets. The medicinally active compound-target network was constructed using Cytoscape 3.9.0. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Results We obtained 191 active compound targets for Gancao (Glycyrrhizae Radix et Rhizoma), 171 for Huangqi (Astragali Radix), and 103 for Chuanwu (Radix Aconiti) (hypoaconitine’s target was obtained through literature and SwissTargetPrediction). A total of 5872 genes were obtained for RA. A drug-active compound-target network involving 13 effect-enhancing and nine toxicity reduction targets was constructed. PGR was the main effect enhancement target, and KCNH2 was the main toxicity reduction target. The effect-enhancing targets were related to 23 GO terms (such as positive regulation of transcription from RNA polymerase II promoter, steroid hormone-mediated signaling pathway, plasma membrane, and protein binding) (P < 0.01), and 13 KEGG pathways related to synergism [such as estrogen signaling pathway, cholinergic synapse, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway]. The toxicity reduction targets were related to 28 GO terms (mainly involes G-protein coupled receptor signaling pathway, plasma membrane, and drug binding) (P < 0.01), and five KEGG pathways related to toxicity reduction (cholinergic synapse, calcium signaling pathway, regulation of actin cytoskeleton, neuroactive ligand-receptor interaction, and serotonergic synapse). Conclusion The combination of Chuanwu (Aconiti Radix) and Huangqi (Astragali Radix) plays an important effect-enhancing role in WTD and involves the estrogen and PI3K/Akt signaling pathways, with PGR as the core. The Chuanwu (Aconiti Radix) and Gancao (Glycyrrhizae Radix et Rhizoma) combination decreases toxicity in WTD and is associated with the cholinergic synapse and calcium signaling pathways, with KCNH2 as the core.

Identification of Differentially Expressed Genes and Pathways Involved in Growth and Development of Mesona chinensis Benth Under Red- and Blue-Light Conditions.

Mesona chinensis Benth (MCB) is an important Chinese herbal medicine. The plant factories might be one of the ways to solve the shortage of MCB supply. In this study, the MCB seedlings were treated under the red (R) and blue (B) lights in the plant factory. Results showed that the red light promoted the growth and development of MCB in comparison with the blue light. Under the red-light condition, the biomass, plant height, and root characteristics were significantly higher than those under blue-light condition, while the soil and plant analyzer development (SPAD) under the red-light treatment was significantly lower than that under the blue-light treatment. Red light also significantly promoted the content of soluble sugar and pectin of MCB compared with blue light. Transcriptome analysis showed that a total of 4,165 differentially expressed genes (DEGs) were detected including 2,034 upregulated and 2,131 downregulated. Of these, 1,112 DEGs including 410 upregulated and 702 downregulated genes were associated with 111 pathways. Moreover, a total of 8,723 differentially expressed transcription factors (TFs) were identified in R vs. B, and these TFs were distributed in 56 gene families. Metabonomic results revealed that a total of 184 metabolites and 99 differentially expressed metabolites (DEMs) (42 upregulated and 57 downregulated) were identified in the red- and blue-light treatments. Integrative analysis of transcriptome and metabolome unveiled that a total of 24 pathways included 70 compounds (metabolites) and were associated with 28 unigenes. In particular, these pathways included starch and sucrose metabolism, phenylpropanoid biosynthesis, cysteine and methionine metabolism, glycolysis/gluconeogenesis, and pentose and glucuronate interconversions. The unigenes included asparagine synthetase (AS), thymidine kinase (TK), alpha, alpha-trehalose-phosphate synthase (TPS), phosphatase IMPL1 (IMPL1), dihydroflavonol 4-reductase (D4R), and 4-coumarate-CoA ligase-like 6 (4CL6), bifunctional aspartokinase-homoserine dehydrogenase 1 (thrA), and abscisic acid 8'-hydroxylase 2 isoform X1 (ABA8). It was indicated that these pathways and genes might play important roles in the growth and development of MCB. This study laid a foundation for the future research of MCB.

High-Throughput Screen of Natural Compounds and Biomarkers for NSCLC Treatment by Differential Expression and Weighted Gene Coexpression Network Analysis (WGCNA).

Lung cancer is known as the leading cause which presents the highest fatality rate worldwide; non-small-cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with high severity and affects 80% of patients with lung malignancies. Up to now, the general treatment for NSCLC includes surgery, chemotherapy, and radiotherapy; however, some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in lung cancer. Therefore, it is necessary to investigate the chemical composition and underlying antitumor mechanisms of TCM, so as to get a better understanding of the potential natural ingredient for lung cancer treatment. In this study, we selected 78 TCM to treat NSCLC cell line (A549) and obtained 92 transcriptome data; differential expression and WGCNA were applied to screen the potential natural ingredient and target genes. The sample which was treated with A. pierreana generated the most significant DEG set, including 6130 DEGs, 2479 upregulated, and 3651 downregulated. KEGG pathway analyses found that four pathways (MAPK, NF-kappa B, p53, and TGF-beta signaling pathway) were significantly enriched; 16 genes were significantly regulated in these four pathways. Interestingly, some of them such as EGFR, DUSP4, IL1R1, IL1B, MDM2, CDKNIA, and IDs have been used as the target biomarkers for cancer diagnosis and therapy. In addition, classified samples into 14 groups based on their pharmaceutical effects, WGCNA was used to identify 27 modules. Among them, green and darkgrey were the most relevant modules. Eight genes in the green module and four in darkgrey were identified as hub genes. In conclusion, we screened out three new TCM (B. fruticose, A. pierreana, and S. scandens) that have the potential to develop natural anticancer drugs and obtained the therapeutic targets for NSCLC therapy. Our study provides unique insights to screen the natural components for NSCLC therapy using high-throughput transcriptome analysis.

High-Throughput In Vitro Gene Expression Profile to Screen of Natural Herbals for Breast Cancer Treatment.

Breast cancer has surpassed lung cancer as the most commonly diagnosed cancer in women worldwide. Some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in breast cancer. However, the chemical composition and underlying anti-tumor mechanisms of TCM still need to be investigated. The primary aim of this study is to provide unique insights to screen the natural components for breast cancer therapy using high-throughput transcriptome analysis. Differentially expressed genes were identified based on two conditions: single samples and groups were classified according to their pharmaceutical effect. Subsequently, the sample treated with E. cochinchinensis Lour. generated the most significant DEGs set, including 1,459 DEGs, 805 upregulated and 654 downregulated. Similarly, group 3 treatment contained the most DEGs (414 DEGs, 311 upregulated and 103 downregulated). KEGG pathway analyses showed five significant pathways associated with the inflammatory and metastasis processes in cancer, which include the TNF, IL-17, NF-kappa B, MAPK signaling pathways, and transcriptional misregulation in cancer. Samples were classified into 13 groups based on their pharmaceutical effects. The results of the KEGG pathway analyses remained consistent with signal samples; group 3 presents a high significance. A total of 21 genes were significantly regulated in these five pathways, interestingly, IL6, TNFAIP3, and BRIC3 were enriched on at least two pathways, seven genes (FOSL1, S100A9, CXCL12, ID2, PRS6KA3, AREG, and DUSP6) have been reported as the target biomarkers and even the diagnostic tools in cancer therapy. In addition, weighted correlation network analysis (WGCNA) was used to identify 18 modules. Among them, blue and thistle2 were the most relevant modules. A total of 26 hub genes in blue and thistle2 modules were identified as the hub genes. In conclusion, we screened out three new TCM (R. communis L., E. cochinchinensis Lour., and B. fruticosa) that have the potential to develop natural drugs for breast cancer therapy, and obtained the therapeutic targets.

Study of TCM Syndrome Identification Modes for Patients with Type 2 Diabetes Mellitus Based on Data Mining.

OBJECTIVE: To establish the diagnosis model for syndromes of type 2 diabetes mellitus (T2-DM) and explore symptoms, the pulse and tongue signs, and laboratory indexes related to syndromes of T2-DM. METHODS: A syndromatologic and laboratory investigation was conducted in 554 T2-DM patients with 58 symptoms, 14 tongue signs, 6 pulse signs, and 12 laboratory indexes. The clinical data on the syndrome were collected and analyzed by using logistic regression analysis, decision tree, and K-nearest neighbor to establish a diagnostic model for effectively distinguishing the typical syndromes in T2-DM patients. RESULTS: The most typical syndromes revealed in T2-DM were stomach heat flourishing (SHF) syndrome (261 patients, accounting for 47.1%) and Qi-Yin deficiency (QYD) syndrome (293 patients, 52.9%). According to the clinical data of the patients with these two syndromes, variables including 6 symptoms and signs, 2 pulse signs, 1 tongue sign, and 2 laboratory indicators were introduced into the logistic regression model. All of them were statistically significant. Then, a diagnostic model constructed by QUEST and CHAID algorithms of the decision tree for identifying the two syndromes was proved to have an accurate diagnostic rate of 85.2%. It was found that the following sign and symptoms were effective to differentiate these two syndromes: odor in the mouth, polyphagia, vulnerability to starvation, burning sensation in the stomach, fatigue, limb weakness, slippery and replete pulse, weak pulse, pink tongue, oral glucose tolerance test, and hemoglobin A1C. A classification model constructed by the K-nearest neighbor method to identify the two syndromes showed an accurate diagnostic rate of 88.3%. Three major statistically significant predictors included in the model were slippery and replete pulse, polyphagia, and weak pulse (P < 0.05). CONCLUSION: A model for distinguishing the two typical syndromes (SHF syndrome and QYD syndrome) in T2-DM patients was effectively established. This model could help to provide methodological support for the standardization of traditional Chinese medicine (TCM) syndrome differentiation methods.

Sulfur Regulates the Trade-Off Between Growth and Andrographolide Accumulation via Nitrogen Metabolism in Andrographis paniculata.

Nitrogen (N) and sulfur (S) are essential mineral nutrients for plant growth and metabolism. Here, we investigated their interaction in plant growth and andrographolide accumulation in medicinal plant Andrographis paniculata grown at different N (4 and 8 mmol·L-1) and S concentration levels (0.1 and 2.4 mmol L-1). We found that increasing the S application rate enhanced the accumulation of andrographolide compounds (AGCs) in A. paniculata. Simultaneously, salicylic acid (SA) and gibberellic acid 4 (GA4) concentrations were increased but trehalose/trehalose 6-phosphate (Tre/Tre6P) concentrations were decreased by high S, suggesting that they were involved in the S-mediated accumulation of AGCs. However, S affected plant growth differentially at different N levels. Metabolite analysis revealed that high S induced increases in the tricarboxylic acid (TCA) cycle and photorespiration under low N conditions, which promoted N assimilation and S metabolism, and simultaneously increased carbohydrate consumption and inhibited plant growth. In contrast, high S reduced N and S concentrations in plants and promoted plant growth under high N conditions. Taken together, the results indicated that increasing the S application rate is an effective strategy to improve AGC accumulation in A. paniculata. Nevertheless, the interaction of N and S affected the trade-off between plant growth and AGC accumulation, in which N metabolism plays a key role.

Polydatin protects Schwann cells from methylglyoxal induced cytotoxicity and promotes crushed sciatic nerves regeneration of diabetic rats.

Oxidative stress plays the main role in the pathogenesis of diabetes mellitus and peripheral neuropathy. Polydatin (PD) has been shown to exhibit strong antioxidative and antiinflammatory effects. At present, no research has focused on the possible effects of PD on Schwann cells and impaired peripheral nerves in diabetic models. Here, we used an in vitro Schwann cell damage model induced by methylglyoxal and an in vivo diabetic sciatic nerve crush model to study problems in such an area. In our experiment, we demonstrated that PD potently alleviated the decrease of cellular viability, prevented reactive oxygen species generation, and suppressed mitochondrial depolarization as well as cellular apoptosis in damaged Schwann cells. Moreover, we found that PD could upregulate Nrf2 and Glyoxalase 1 (GLO1) expression and inhibit Keap1 and receptor of AGEs (RAGE) expression of damaged Schwann cells. Finally, our in vivo experiment showed that PD could promote sciatic nerves repair of diabetic rats. Our results revealed that PD exhibited prominent neuroprotective effects on Schwann cells and sciatic nerves in diabetic models. The molecular mechanisms were associated with activating Nfr2 and GLO1 and inhibiting Keap1 and RAGE.

Improving Small Intestinal Motility in Experimental Acute Necrotising Pancreatitis by Modulating the CPI-17/MLCP Pathway Using Chaiqin Chengqi Decoction.

Protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), a specific inhibitor of myosin light-chain phosphatase (MLCP) regulated by proinflammatory cytokines, is central for calcium sensitisation. We investigated the effects of chaiqin chengqi decoction (CQCQD) on the CPI-17/MLCP pathway in the small intestinal smooth muscle cells (SMCs) and strips (SMS) in an AP model. Necrotising AP was induced in rats by intraperitoneal injections (IPI) of L-ornithine (3.0 g/kg, pH 7.0; hourly × 2) at 1 hour apart; controls received saline. In treatment groups, carbachol (CCh; 60 µg/kg, IPI) or CQCQD (20 g/kg; 2-hourly × 3, intragastric) was administered. The necrotising AP model was associated with systemic inflammation (serum IL-1ß and TNF-α) and worsened jejunum histopathology and motility (serum vasoactive intestinal peptide and intestinal fatty acid-binding protein) as the disease progressed. There was decreased intracellular calcium concentration ([Ca2+]i) SMCs. Contractile function of isolated SMCs was reduced and associated with down-regulated expression of key mRNAs and proteins of the CPI-17/MLCP pathway as well as increased IL-1ß and TNF-α. CQCQD and CCh significantly reversed these changes and the disease severity. These data suggest that CQCQD can improve intestinal motility by modulating the CPI-17/MLCP pathway in small intestinal smooth muscle during AP.

Role of Metabolic Activation in Elemicin-Induced Cellular Toxicity.

Elemicin, an alkenylbenzene constituent of natural oils of several plant species, is widely distributed in food, dietary supplements, and medicinal plants. 1'-Hydroxylation is known to cause metabolic activation of alkenylbenzenes leading to their potential toxicity. The aim of this study was to explore the relationship between elemicin metabolism and its toxicity through comparing the metabolic maps between elemicin and 1'-hydroxyelemicin. Elemicin was transformed into a reactive metabolite of 1'-hydroxyelemicin, which was subsequently conjugated with cysteine (Cys) and N-acetylcysteine (NAC). Administration of NAC could significantly ameliorate the elemicin- and 1'-hydroxyelemicin-induced cytotoxicity of HepG2 cells, while depletion of Cys with diethyl maleate (DEM) increased cytotoxicity. Recombinant human CYP screening and CYP inhibition experiments revealed that multiple CYPs, notably CYP1A1, CYP1A2, and CYP3A4, were responsible for the metabolic activation of elemicin. This study revealed that metabolic activation plays a critical role in elemicin cytotoxicity.

Post-marketing Re-evaluation of Tongxiening Granules () in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Multi-center, Randomized, Double-Blind, Double-Dummy and Positive Control Trial.

OBJECTIVE: To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). METHODS: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. RESULTS: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). CONCLUSION: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

Metabolic Activation of Myristicin and Its Role in Cellular Toxicity.

Myristicin is widely distributed in spices and medicinal plants. The aim of this study was to explore the role of metabolic activation of myristicin in its potential toxicity through a metabolomic approach. The myristicin- N-acetylcysteine adduct was identified by comparing the metabolic maps of myristicin and 1'-hydroxymyristicin. The supplement of N-acetylcysteine could protect against the cytotoxicity of myristicin and 1'-hydroxymyristicin in primary mouse hepatocytes. When the depletion of intracellular N-acetylcysteine was pretreated with diethyl maleate in hepatocytes, the cytotoxicity induced by myristicin and 1'-hydroxymyristicin was deteriorated. It suggested that the N-acetylcysteine adduct resulting from myristicin bioactivation was closely associated with myristicin toxicity. Screening of human recombinant cytochrome P450s (CYPs) and treatment with CYP inhibitors revealed that CYP1A1 was mainly involved in the formation of 1'-hydroxymyristicin. Collectively, this study provided a global view of myristicin metabolism and identified the N-acetylcysteine adduct resulting from myristicin bioactivation, which could be used for understanding the mechanism of myristicin toxicity.