Using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry, network pharmacology, and molecular docking to explore the constituent targets and action mechanisms of decoction of Angelica sinensis, Zingiberis Rhizoma Recens, and Mutton in the treatment of diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic intestinal disorder characterized by abdominal discomfort, stool characteristics, and changes in bowel habits. Among them, diarrhea-type (diarrhea-predominant irritable bowel syndrome, abbreviated as IBS-D) is the most common. Because its pathogenesis is not understood, symptomatic treatment is currently used in clinical practice, and its long-term effect is still unclear. Decoction of Angelica sinensis, Zingiberis Rhizoma Recens, and Mutton (DAZM) is a famous traditional Chinese medicine recipe created by Zhang Zhongjing, a famous doctor in the Eastern Han Dynasty 2000 years ago, and is still in use today. Our research team has previously investigated the clinical study of DAZM in the treatment of IBS-D and conducted animal experiment research, indicating that DAZM has a significant effect on improving IBS-D. Yet, there are few reports on the specific mechanism of action of DAZM in improving the treatment of IBS and related types. Most studies discuss and verify its efficacy and protection from a clinical perspective. For this reason, this research will explore the constituent targets and mechanisms of DAZM to improve the treatment of IBS-D, provide relevant scientific evidence, and also provide reference evidence for the efficacy of food therapy decoction in improving the treatment of diseases and mechanism to open up new experimental research ideas. METHODS: Identification of drug ingredients and collection of targets for DAZM using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine database, active ingredients were selected based on their oral bioavailability and drug-like properties. Obtained IBS-D targets using the GeneCards database, took the intersection of IBS-D targets and DAZM targets and obtained potential targets of DAZM for the treatment of IBS-D. Using Cytoscape software to draw a network diagram of "Food therapy decoction-ingredient-target-disease" and selected the ingredients with larger parameter values by topological analysis. Correlation analysis of the selected active and parametric ingredients with prominent symptoms of IBS-D using SymMap database, and selection of potential core ingredients. The construction of protein interaction networks from the String database and the selection of potential core targets. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses using the Metascape database, establishing the bioinformatic processes and signaling pathways involved. Molecular docking of core ingredients and potential core targets was performed using AutoDock Vina, and the results were visualized using Python molecule (PyMOL) and LigPlus+. Finally, based on the results of this research combined with previous literature reports, the discussion section of this paper summarizes in detail the key core ingredients, targets, and signaling pathways of DAZM in improving IBS-D. RESULTS: DAZM may act on eight potential core targets (threonine kinase 1, insulin, tumour necrosis factor, tumour protein p53, interleukin 6, epidermal growth factor receptor, connexin ß1, and interleukin 1ß) through eight core ingredients (Zingiberone, Shyobunone, Palmitic acid, Sebiferic acid, ß-Bisabolene, ß-Sitosterol, Stigmasterol, and Oleic acid). inhibit pro-inflammatory factors through Advanced Glycation End Products-Receptor (AGE-RAGE) signaling pathway, Cyclic Adenosine Monophosphate (cAMP) signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Calmodulin (CaM) signaling pathway, and other pathways. It can alleviate the inflammatory response, enhance the intestinal mucosal barrier and regulate intestinal motility, and play a role in the treatment and improvement of IBS-D. CONCLUSIONS: This research mainly found the mechanism of DAZM on IBS-D, which may involve multiple ingredients, multiple targets, and multiple pathways. DAZM with medicinal and edible functions can effectively improve the treatment of IBS-D. This kind of dietary therapy is suitable for long-term treatment and is worthy of promotion.

Effects of decoction of Angelica Sinensis, Zingiberis Rhizoma Recens, and mutton on physiology and biochemistry of Sprague Dawley female rats with spleen-kidney Yang deficiency.

Background: To examine the effects of each dose of decoction of Angelica sinensis (Dang gui), Zingiberis Rhizoma Recens (Sheng jiang), and mutton (DAZM) on the physiological and biochemical indexes of female rats with spleen-kidney Yang deficiency (SKYD) through 30-day feeding of DAZM, and to evaluate the tonifying effect of DAZM combined with the system of benefit damage index-general score (BDI-GS). Methods: Sprague Dawley (SD) rats were administered adenine and senna water to establish a SKYD model. The rats were then allocated to 4 groups at random: Model group, and L group, 4.2 g/kg, M group, 8.4 g/kg and H group, 16.8 g/kg. In addition, the group of normal feeding with unlimited diet was set as N group. Blood samples were taken to detect the relevant physiological and biochemical indexes. For organ coefficient analysis, 10 kinds of organ tissues were dissected and weighed. The tonifying effect of DAZM was discussed according to the BDI-GS system. Results: During the modeling, the weight of rats in the normal group displayed a marked growth trend, and the weight of the model group was markedly lower than that of the normal group. After feeding the rats DAZM at a low, intermediate, and high dose, the anal temperature of rats in each group continued to rise, and finally remained basically the same as that of normal rats. Hematological and urine examinations revealed that the urea nitrogen and creatinine (CRE) of the model group and the experimental group were markedly higher than those of the normal group, and there were marked differences. After intragastric administration of DAZM, E2 increased markedly. The BDI-GS values of the liver, spleen, lung, kidney, brain, ovary, and adrenal gland of female rats in the 3 administration groups of DAZM were >1, and the total cumulative GS value of each organ of female rats was more than 10. Conclusions: The decoction of DAZM has no obvious effect on the growth, metabolism, and development of female rats with SKYD, causes no obvious damage to organs, and has a certain reparative effect on the kidney damage caused by SKYD.

Salvia miltiorrhiza extract may exert an anti-obesity effect in rats with high-fat diet-induced obesity by modulating gut microbiome and lipid metabolism.

BACKGROUND: Studies have shown that a high-fat diet (HFD) can alter gut microbiota (GM) homeostasis and participate in lipid metabolism disorders associated with obesity. Therefore, regulating the construction of GM with the balance of lipid metabolism has become essential for treating obesity. Salvia miltiorrhiza extract (Sal), a common traditional Chinese medicine, has been proven effective against atherosclerosis, hyperlipidemia, obesity, and other dyslipidemia-related diseases. AIM: To investigate the anti-obesity effects of Sal in rats with HFD-induced obesity, and explore the underlying mechanism by focusing on GM and lipid metabolism. METHODS: Obesity was induced in rats with an HFD for 7 wk, and Sal (0.675 g/1.35 g/2.70 g/kg/d) was administered to treat obese rats for 8 wk. The therapeutic effect was evaluated by body weight, body fat index, waistline, and serum lipid level. Lipid factors (cAMP, PKA, and HSL) in liver and fat homogenates were analyzed by ELISA. The effect of Sal on GM and lipid metabolism was assessed by 16S rRNA-based microbiota analysis and untargeted lipidomic analysis (LC-MS/MS), respectively. RESULTS: Sal treatment markedly reduced weight, body fat index, serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein, glucose, free fatty acid, hepatic lipid accumulation, and adipocyte vacuolation, and increased serum high-density lipoprotein (HDL-C) in rats with HFD-induced obesity. These effects were associated with increased concentrations of lipid factors such as cAMP, PKA, and HSL in the liver and adipose tissues, enhanced gut integrity, and improved lipid metabolism. GM analysis revealed that Sal could reverse HFD-induced dysbacteriosis by promoting the abundance of Actinobacteriota and Proteobacteria, and decreasing the growth of Firmicutes and Desulfobacterita. Furthermore, LC-MS/MS analysis indicated that Sal decreased TGs (TG18:2/18:2/20:4, TG16:0/18:2/22:6), DGs (DG14:0/22:6, DG22:6/22:6), CL (18:2/ 18:1/18:1/20:0), and increased ceramides (Cers; Cer d16:0/21:0, Cer d16:1/24:1), (O-acyl)-ω-hydroxy fatty acids (OAHFAs; OAHFA18:0/14:0) in the feces of rats. Spearman's correlation analysis further indicated that TGs, DGs, and CL were negatively related to the abundance of Facklamia and Dubosiella, and positively correlated with Blautia and Quinella, while OAHFAs and Cers were the opposite. CONCLUSION: Sal has an anti-obesity effect by regulating the GM and lipid metabolism.

Comparison of high or modified low tie of the inferior mesenteric artery in laparoscopic rectal cancer surgery: A meta-analysis.

OBJECTIVE: The purpose of this study was to perform a meta-analysis comparing the oncological, intraoperative and safety outcomes in laparoscopic rectal cancer surgery with and without preservation of the left colic artery (LCA). METHOD: We searched several databases including PubMed, Web of Science, Cochrane Library, and Embase databases. This meta-analysis included randomized clinical trials, prospective, and retrospective comparative studies regarding high- or modified low-tie ligation of the inferior mesenteric artery in laparoscopic rectal cancer surgery. RESULTS: Of 641 potentially eligible articles, 16 studies with 3050 participants met the eligibility criteria and were included in the meta-analysis. There was no significant difference in estimated blood loss (WMD -2.63, 95% CI -5.69 to 0.43; P = .09), the number of harvested lymph nodes (WMD -0.35, 95% CI -1.60 to 0.20; P = .50), the number of apical lymph node yield (WMD -0.19, 95% CI -0.52 to 0.13; P = .24), the number of apical lymph node metastasis (OR 0.76, 95% CI 0.40 to 1.45; P = .40), rate of conversion to open surgery (OR 0.74, 95% CI 0.50 to 1.09; P = .513), rate of urinary dysfunction (OR 1.39, 95% CI 0.71 to 2.74; P = .34), rate of recurrence and metastasis (OR 1.10, 95% CI 0.75 to 1.61; P = .64), 5-year survival rate (OR 0.89, 95% CI 0.67 to 1.18; P = .42). However, this meta-analysis demonstrated a statistically significant difference in operating time (WMD -9.92, 95% CI -15.49 to -5.84; P = .0005), rate of diverting stom (OR 1.42, 95% CI 1.06 to 1.92; P = .02), rate of anastomotic leakage (OR 2.673, 95% CI 1.91 to 3.62; P < .00001), time to first flatus (WMD 0.29, 95% CI 0.11 to 0.48; P = .002), time of hospitalization (WMD 0.64, 95% CI 0.14 to 1.15; P = .01) between the 2 surgical techniques. COCLUSION: The available evidence suggests that preserving the left colic artery is a safe, effective technique for patients with laparoscopic rectal cancer. nique for patients with laparoscopic rectal cancer.

Sishen Pill Ameliorates Dextran Sulfate Sodium (DSS)-Induced Colitis with Spleen-Kidney Yang Deficiency Syndromes: Role of Gut Microbiota, Fecal Metabolites, Inflammatory Dendritic Cells, and TLR4/NF-κB Pathway.

Sishen pill (SSP) is an old Chinese medicine used to treat colitis with spleen-kidney-yang deficiency (SKYD) syndromes. However, its exact mechanism of action has not yet been fully elucidated. The aim of this study was to evaluate the effects and potential mechanisms of SSP on colitis with SKYD syndromes in mice. Colitis with SKYD syndromes was induced by rhubarb, hydrocortisone, and dextran sulfate sodium (DSS), and treatment was provided with SSP. Flow cytometry was performed to examine the inflammatory dendritic cell (infDC) regulations of SSP. The changes in the gut microbiota (GM) and fecal metabolites post-SSP treatment were investigated using the combination of 16S rRNA sequencing and untargeted metabolomics. Additionally, we also examined whether SSPs could regulate the infDCs by modifying TLR4/NF-κB signaling pathways. Compared with the DSS group, the disease activity index, colonic weight, index of colonic weight, and colonic injury scores, as well as the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-12p70 decreased significantly in the DSS + SSP group, while free triiodothyronine (FT3), free tetraiodothyronine (FT4), testosterone (TESTO), body weight change, colonic length, and the levels of IL-10 increased. Also, SSP decreased the amounts of CD103+CD11c+iNOS+, CD103+CD11c+TNF-α +, CD11c+CD103+CD324+, CD103+CD11c+MHC-II+, and CD103+CD11c+CD115+. Interestingly, 16S rRNA sequencing and untargeted metabolomics showed that SSP treatment restored the dysbiosis of GM and improved the dysfunction in fecal metabolism in colitis mice with SKYD syndromes. Correlation analysis indicated that the modulatory effects of SSP on FT3, FT4, IL-10, colonic weight index, CD103+CD11c+TNF-α +, CD103+CD11c+MHC-II+, and 13 common differential metabolites were related to alterations in the abundance of Parvibacter, Aerococcus, norank_f_Lachnospiraceae, Lachnospiraceae_UCG-006, Akkermansia, and Rhodococcus in the GM. In addition, SSP markedly inhibited the activation of the TLR4, MyD88, TRAF6, TAB2, and NF-κBp65 proteins and activated IκB. These results indicate that SSP can effectively alleviate colitis mice with SKYD syndrome by regulating infDCs, GM, fecal metabolites, and TLR4/NF-κB signaling pathways.

Identification of Key Genes in Atherosclerosis by Combined DNA Methylation and miRNA Expression Analyses.

BACKGROUND: Atherosclerosis is a significant cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. The objective of this study was to identify the key genes aberrantly expressed in atherosclerosis, which were regulated by microRNAs and DNA methylation. METHODS: We acquired data on DNA methylation and microRNA and messenger RNA expression from Gene Expression Omnibus data sets (GSE46394, GSE53675, and GSE12288, respectively) and identified differentially methylated genes, differentially expressed genes, and differentially expressed microRNAs between atherosclerosis and control samples. The miRDB, miRTarBase, and TargetScan databases were used to predict differentially expressed microRNAs-targeted genes, which were then intersected with differentially methylated genes and differentially expressed genes to identify genes associated with aberrant DNA methylation and microRNA activity. The DAVID database was used to perform functional enrichment analysis of differentially methylated genes and the key genes involved in atherosclerosis. Potential therapeutic agents for atherosclerosis were predicted by Connectivity Map analysis. RESULTS: In total, we identified 47 upregulated hypomethylated and 90 downregulated hypermethylated genes in atherosclerosis. Among them, 24 differentially expressed genes were found to be modulated both through aberrant DNA methylation and microRNA expression, and 10 such differentially expressed genes were defined as the key genes in atherosclerosis. Fifteen chemicals were selected for their potential effect in . CONCLUSIONS: We identified 10 key genes significantly associated with aberrant DNA methylation and microRNA expression in atherosclerosis and suggested 15 chemicals with potential effects on these genes, which could be further investigated as candidate drugs for atherosclerosis.

Curcumin Inhibits T Follicular Helper Cell Differentiation in Mice with Dextran Sulfate Sodium (DSS)-Induced Colitis.

Follicular helper T cells (Tfh) regulate the differentiation of germinal center B cells and maintain humoral immunity. Notably, imbalances in Tfh differentiation often lead to the development of autoimmune diseases, including inflammatory bowel disease (IBD). Curcumin, a natural product derived from Curcuma longa, is effective in relieving IBD in humans and animals, and its mechanisms of immune regulation need further elaboration. In this study, dextran sodium sulfate induced ulcerative colitis in BALB/c mice, and curcumin was administered simultaneously for 7 days. Curcumin effectively upregulated the change rate of mouse weight, colonic length, down-regulated colonic weight, index of colonic weight, colonic damage score and the levels of pro-inflammatory cytokines IL-6, IL-12, IL-23 and TGF-[Formula: see text]1 in colonic tissues of colitis mice. Importantly, curcumin regulated the differentiation balance of Tfh and their subpopulation in colitis mice; the percentages of Tfh (CD4[Formula: see text]CXCR5[Formula: see text]BCL-6[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-L1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]ICOS[Formula: see text], Tfh17 and Tem-Tfh were downregulated significantly, while CD4[Formula: see text]CXCR5[Formula: see text]Blimp-1[Formula: see text], Tfh1, Tfh10, Tfh21, Tfr, Tcm-Tfh and Tem-GC Tfh were upregulated. In addition, curcumin inhibited the expression of Tfh-related transcription factors BCL-6, p-STAT3, Foxp1, Roquin-1, Roquin-2 and SAP, and significantly upregulated the protein levels of Blimp-1 and STAT3 in colon tissue. In conclusion, curcumin may be effective in alleviating dextran sulfate sodium-induced colitis by regulating Tfh differentiation.

Treatment and mechanism of fecal microbiota transplantation in mice with experimentally induced ulcerative colitis.

Restoring intestinal microbiota dysbiosis with fecal microbiota transplantation is considered as a promising treatment for ulcerative colitis. However, the mechanisms underlying its relieving effects remain unclear. Ulcerative colitis pathogenesis is associated with the involvement of immune cells and inflammatory cytokines. Here, we aimed to investigate the effect of fecal microbiota transplantation on T cell cytokines in a dextran sulfate sodium-induced ulcerative colitis mouse model. Five-aminosalicylic acid (5-ASA) was used as the positive control. Male C57BL/6 mice were randomly assigned to control, model (UC), UC + FMT, and UC + 5-ASA groups. Each group consisted of five mice. The establishment of the mouse model was verified by fecal occult-blood screening and hematoxylin-eosin staining. Results showed that fecal microbiota transplantation reduced colonic inflammation, significantly decreased T helper (Th)1 and Th17 cells, interferon-gamma, interleukin-2 and interleukin-17, as well as significantly increased Th2 and regulatory T (Treg) cells, interleukin-4, interleukin-10, and transforming growth factor-beta, and improved routine blood count. Furthermore, 16S rRNA gene-sequencing analysis showed a significant increase in the relative abundance of genus Akkermansia and a significant decrease in the relative abundance of genus Helicobacter in the ulcerative colitis group. Fecal microbiota transplantation restored the profile of the intestinal microbiota to that of the control group. These findings demonstrated the capability of fecal microbiota transplantation in controlling experimentally induced ulcerative colitis by improving Th1/Th2 and Th17/Treg imbalance through the regulation of intestinal microbiota.

Moxibustion therapy on myofascial pain syndrome: An evidence-based clinical practice guideline.

BACKGROUND: Myofascial pain syndrome (MPS) is a chronic systemic pain disorder. Among the common treatments, moxibustion has an irreplaceable therapeutic effect and is an effective Traditional Chinese Medicine therapy for MPS. However, the lack of clinical practice guidelines (CPGs) has prompted the publication of guidelines on the use of moxibustion in the treatment of MPS. METHODS: The clinical practice guideline will base on the Institute of Medicine, the World Health Organization guideline handbook, the Grade of Recommendations Assessment, Development, and Evaluation the Appraisal of Guidelines for Research & Evaluation II, Reporting Items for practice, Guideline in Healthcare and recommendations thereof will be made on the basis of systematic reviews. We will establish a guidelines development team that will draft clinical questions in the form of population, intervention, comparison, results and conduct a literature search and quality of evidence assessment. The experts will make recommendations after 2 or 3 rounds of Delphi investigations. We will carefully consider the patient's values and preferences and conduct a peer review. ETHICS AND DISSEMINATION: The guidelines will not contain any personal data and will not prejudice individual rights, so no ethical approval will be required. The guidelines will be subject to rigorous peer review and may be published in a journal or circulated at relevant conferences. RESULTS: The guidelines will be published in relevant peer-reviewed journals. CONCLUSION: This guideline will make it easier for clinicians to treat MPs in the clinical setting and improve the effectiveness of treatment for MPS. STUDY REGISTRATION: The study is registered with the International Practice Guideline Registry Platform (IPGRP): IPGRP-2020CN030.

Acupuncture and moxibustion therapy for scapulohumeral periarthritis: Protocol for an overview of systematic reviews and meta-analysis.

BACKGROUND: Scapulohumeral periarthritis (SP) is a very common painful shoulder disorder. Several systematic reviews (SRs) and meta-analyses have reported the effectiveness of acupuncture for patients with SP. However, the evidence has not been systematically synthesized. This overview aims to map, synthesize, and assess the reliability of evidence generated from these SRs and meta-analyses of acupuncture for SP. METHODS: We will electronically search the following databases for literature, regardless of publication status and language: the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; China National Knowledge Infrastructure (CNKI); Chinese Biomedical Literature Database (CBM); Chinese Scientific Journal Database (VIPdatabase); and Wan-Fang Database. In order to ensure the comprehensiveness and accuracy of the literature retrieval, we will combine the Suggestions of evidence-based medicine experts with the actual situation in the literature retrieval process to formulate the retrieval strategy, and make corresponding records to find the most appropriate retrieval strategy. The reference lists and the citation lists of studies meeting the inclusion criteria and relevant SRs will also be searched to identify further studies for inclusion. Before this review completed, the two reviewers will conduct the searching once again to ensure the latest studies could be included. ETHICS AND DISSEMINATION: Ethical approval is not required for overviews. We plan to publish results in peer-reviewed journals and present at international and national academic, clinical, and patient conferences. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: This overview will provide comprehensive evidence of acupuncture for patients with SP. INPLASY REGISTRATION NUMBER: INPLASY202060020.

Which acupuncture and moxibustion technique is more effective for primary dysmenorrhea: A protocol for a network meta-analysis of randomized controlled trials.

BACKGROUND: Primary dysmenorrhea (PD), also called functional dysmenorrhea, refers to a woman's menstrual period in genital no organic disease, abdominal pain, under the belly and other discomfort for the characteristics of disease of department of gynecology. Acupuncture and moxibustion have been accepted as treatment options for PD. So far, there are so many therapies for PD and their efficacy has been assessed by several systematic reviews. Therefore, this study aims at evaluating the effectiveness which acupuncture and moxibustion technique is more effective for primary dysmenorrhea. METHODS AND ANALYSIS: The following electronic databases will be searched in this study: the Cochrane Central Register of Controlled Trials (CENTRAL);PubMed; EMBASE; China National Knowledge Infrastructure (CNKI); Chinese Biomedical Literature Database (CBM);Chinese Scientific Journal Database (VIP database); and Wan-Fang Database(WF). More than two authors independently assessed the quality of the evidence by AMSTAR2, PRISMA, PRISMA-A, and GRADE approach. Two of our researchers will use the bias risk tool provided by the Cochrane Collaboration to evaluate the quality of the literature using WinBUGS 1.4.3 and STATA softwares. The primary outcomes include the extent of pain in the lower abdomen measured by visual analog scale (VAS) and relief from symptoms. The quality of life (QoL) and Adverse events will be considered as Additional outcome(s). Their reference lists and the citation lists of studies meeting the inclusion criteria and relevant systematic reviews will also be searched to identify further studies for inclusion. Before this review completed, the 2 reviewers will conduct the search once again to ensure the latest studies could be included. ETHICS AND DISSEMINATION: This review does not require ethical approval. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: This study will provide comprehensive evidence of acupuncture and moxibustion for patients with PD. INPLASY REGISTRATION NUMBER: INPLASY2020500106.

Effect of Sishen Pill on Memory T Cells From Experimental Colitis Induced by Dextran Sulfate Sodium.

Immune memory has a protective effect on the human body, but abnormal immune memory is closely related to the occurrence and development of autoimmune diseases including inflammatory bowel disease (IBD). Sishen Pill (SSP) is a classic prescription of traditional Chinese medicine, which is often used to treat chronic colitis, but it is not clear whether SSP can alleviate experimental colitis by remodeling immune memory. In the present study, the therapeutic effect of SSP on chronic colitis induced by dextran sulfate sodium (DSS) was evaluated by colonic length, colonic weight index, macroscopic and microscopic scores, and pathological observation. The cytokine levels were tested by enzyme-linked immunosorbent assay (ELISA); the percentages of central memory T (Tcm) and effector memory T (Tem) cells were analyze\d by flow cytometry; and activation of phosphoinositide 3-kinase (PI3K)/Akt signaling proteins was measured by western blotting. After 7-days' treatment, SSP alleviated DSS-induced colitis, which was demonstrated by decreased colonic weight index, colonic weight, histopathological injury scores, restored colonic length, gradual recovery of colonic mucosa, and lower levels of interleukin (IL)-2, IL-7, IL-12, and IL-15, while SSP increased IL-10 expression. SSP obviously regulated the quantity and subpopulation of Tcm and Tem cells. Furthermore, SSP markedly inhibited activation of PI3K, Akt, phospho-Akt, Id2, T-bet, forkhead box O3a, Noxa, and C-myc proteins in the PI3K/Akt signaling pathway and activated Rictor, Raptor, tuberous sclerosis complex (TSC)1, TSC2, phospho-AMP-activated kinase (AMPK)-α, AMPK-α, eukaryotic translation initiation factor 4E-binding protein 2, kinesin family member 2a, and 70-kDa ribosomal protein S6 kinase. These results indicate that SSP effectively controls Tem cells in the peripheral blood to relieve experimental colitis induced by DSS, which were potentially related with inhibiting the PI3K/Akt signaling pathway.

Sishen Wan® Ameliorated Trinitrobenzene-Sulfonic-Acid-Induced Chronic Colitis via NEMO/NLK Signaling Pathway.

The nuclear factor (NF)-κB signaling pathway plays an important role in the initialization and development phase of inflammatory injuries, including inflammatory bowel disease (IBD). Sishen Wan (SSW) is a classic Chinese patent medicine listed in the Chinese Pharmacopoeia, which is usually used to treat chronic colitis; however, it is unclear whether SSW can treat IBD via the NF-κB signaling pathway. In the present study, the therapeutic effect of SSW was demonstrated by the decreased index of colonic weight, macroscopic and microscopic score, and pathological observation in chronic colitis induced by trinitrobenzene sulfonic acid. In colonic mucosa of rats with chronic colitis, SSW reduced the levels of calprotectin and eliminated oxidative lesions; downregulated expression of interferon-γ, interleukin (IL)-1ß and IL-17; increased expression of IL-4; and suppressed expression of NF-κB p65, and NF-κB essential modulator (NEMO)-like kinase (NLK). Furthermore, SSW inhibited ubiquitinated NEMO, ubiquitin-activated enzyme, and E2i activation, and phosphorylation of downstream proteins (cylindromatosis protein, transforming growth factor-ß-activated kinase and P38). These results show that the therapeutic effects of SSW in chronic colitis were mediated by inhibiting the NEMO/NLK signaling pathway to suppress NF-κB activation.

Immunoregulatory effects of Tripterygium wilfordii Hook F and its extracts in clinical practice.

Tripterygium wilfordii Hook F (TwHF) and its extracts have long been used for the treatment of rheumatoid arthritis, autoimmune diseases, and kidney disease due to their anti-inflammatory, immunoregulatory, and other pharmacological effects. However, the clinical immunoregulatory effects of TwHF and its extracts remain unclear, so we reviewed their effects for use in clinical practice. This review provides a comprehensive summary of the recent literature on the immunoregulatory effects of TwHF and its extracts in clinical studies. TwHF and its extracts affect the proliferation and activation of Tand B cells; ratio of Tcell subsets; inflammatory response of monocytes, macrophages, and immunoglobulins; and secretion of many cytokines. Together, these effects dictate immune function in a variety of diseases. TwHF and its extracts can be used alone or in combination with existing therapies against many immune disorders through immunomodulation.

Yi Shen Juan Bi Pill Ameliorates Bone Loss and Destruction Induced by Arthritis Through Modulating the Balance of Cytokines Released by Different Subpopulations of T Cells.

The Yi Shen Juan Bi Pill (YSJB), a traditional Chinese compound herbal drug, has been used as an anti-rheumatic drug in clinical practice. Cartilage and bone destruction of inflamed joints is the hallmark of rheumatoid arthritis (RA). Our previous study suggested that YSJB had a protective effect on joint damage in collagen-induced (CIA) rats. However, the role and the mechanism of YSJB in inflammation-induced bone loss are unavailable. The current study aimed to further evaluate the effect of YSJB on the joint destruction and the systemic bone loss, and to clarify the potential mechanism. CIA model was generated by using collagen II and incomplete Freund's adjuvant in Sprague-Dawley rats. After 4 weeks treatment, arthritic index, tissue pathology, micro-computed tomography scanning (µ-CT), and bone mineral density (BMD) analysis were performed. YSJB decreased arthritic scores and bone destruction; improved the BMD of lumbar vertebrae and bone volume fraction of inflamed joints. Moreover, YSJB significantly decreased the production of serum bone resorption markers, including Tartrate-Resistant Acid Phosphatase (TRACP), N-terminal telopeptide of type I collagen and C-terminal telopeptide of type I collagen. Meanwhile, it increased the level of serum bone formation marker type I collagen N-terminal propeptide. These results revealed that YSJB ameliorated bone destruction and reduced bone loss induced by arthritis. We have previously showed that Tregs inhibited osteoclast differentiation and bone resorption in vitro. Furthermore, others suggested that abnormality of Th1, Th17 may contribute to bone destruction. Here, we showed YSJB significantly up-regulated the percentage of Tregs, while also down-regulated the percentage of Th1 and Th17 cells. Our findings provide the evidence that YSJB ameliorates the severity of disease and joint degradation, and reduces systemic bone loss induced by arthritis. We propose YSJB modulates the balance of T cell phenotype, which affects the activation and differentiation of osteoclasts.

Erzhi Pill® Protected Experimental Liver Injury Against Apoptosis via the PI3K/Akt/Raptor/Rictor Pathway.

Erzhi Pill (EZP) is one of the basic prescriptions for treating liver diseases in traditional Chinese medicine. However, its mechanism of action is still undefined. The PI3K/AKT/Raptor/Rictor signaling pathway is closely related to apoptosis and plays a significant role in the pathogenesis of liver disease. To define the mechanism of the hepatoprotective effect of EZP in the treatment of liver disease, hepatic injury induced by 2-acetylaminofluorene/partial hepatectomy was treated by EZP for 14 days. The therapeutic effect of EZP was confirmed by the decreased production of aspartate aminotransferase and alanine aminotransferase, recovery of pathological liver injury, followed by inhibition of pro-inflammatory cytokines and transforming growth factor-ß1. Bromodeoxyuridine assay and TUNEL staining indicated that apoptosis was suppressed and the numbers of cells in S phase and G0/G1phase were decreased. The crucial proteins in the PI3K/AKT/Raptor/Rictor signaling pathway were deactivated in rats with experimental liver injury treated by EZP. These results indicated that the hepatoprotective effect of EZP via inhibition of hepatocyte apoptosis was closely related to repression of the PI3K/Akt/Raptor/Rictor signaling pathway.

Erding Formula in hyperuricaemia treatment: unfolding traditional Chinese herbal compatibility using modern pharmaceutical approaches.

OBJECTIVES: Traditional Chinese herbal formulas are difficult to be understood because of complex compositions and specific therapeutic principles. To better understand herbal compatibility in Traditional Chinese medicine (TCM), this study was conducted to investigate the effects of a Chinese pharmacopoeia-listed formula, Erding Formula (EF) and its constituent herbs for a new indication, hyperuricaemia. METHODS: A hypoxanthine and potassium oxonate-induced hyperuricemic mouse model, a xylene-induced inflammatory mouse model and an acetic acid-induced pain model were used to test the effects of EF and its constituent herbs. In addition, we investigated whether EF and/or its relevant herbs had an impact on the expression of URAT1 and OAT3 mRNA. KEY FINDINGS: The results showed EF and individual herbs had pharmacological effects on selected targets. Only Viola yedoensis Makino (Viola) lowered uric acid levels, while all four herbs had anti-inflammatory and analgesic effects. The EF may lower the uric acid level through inhibiting the expression of URAT1 mRNA and enhancing the expression of OAT3 mRNA. CONCLUSIONS: These findings provide pharmacological insights into the effects of EF and individual herbs on UA excretion. This study suggests that Viola is the main herb in EF. This study facilitates better understanding of TCM principles and theories using modern pharmaceutical approaches.

Erzhi Pill® Repairs Experimental Liver Injury via TSC/mTOR Signaling Pathway Inhibiting Excessive Apoptosis.

The present study aimed to investigate the mechanism of hepatoprotective effect of Erzhi Pill (EZP) on the liver injury via observing TSC/mTOR signaling pathway activation. The experimental liver injury was induced by 2-acetylaminofluorene (2-AAF) treatment combined with partial hepatectomy (PH). EZP treated 2-AAF/PH-induced liver injury by the therapeutic and prophylactic administration. After the administration of EZP, the activities of aspartic transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), and gamma-glutamyl transpeptidase (γ-GT) were decreased, followed by the decreased levels of hepatocyte apoptosis and caspase-3 expression. However, the secretion of albumin, liver weight, and index of liver weight were elevated. Microscopic examination showed that EZP restored pathological liver injury. Meanwhile, Rheb and mammalian target of rapamycin (mTOR) activation were suppressed, and tuberous sclerosis complex (TSC) expression was elevated in liver tissues induced by 2-AAF/PHx and accompanied with lower-expression of Bax, Notch1, p70S6K, and 4E-EIF and upregulated levels of Bcl-2 and Cyclin D. Hepatoprotective effect of EZP was possibly realized via inhibiting TSC/mTOR signaling pathway to suppress excessive apoptosis of hepatocyte.

Acupuncture therapy on apoplectic aphasia rehabilitation.

OBJECTIVE: Acupuncture has often been used for aphasia rehabilitation in China. The purpose of this paper was to: 1) provide a historic overview of acupuncture for aphasia due to stroke; 2) summarize the commonly used acupuncture approaches; and 3) objectively comment on the effectiveness of acupuncture for the rehabilitation of this type of disorder. METHODS: The Elsevier database and a Chinese database (CNKI) were searched through December, 2010 with the key words "aphasia, acupuncture" in English and Chinese, respectively. Case reports, uncontrolled clinical observations and controlled clinical trials were all included if acupuncture was the sole treatment or the main component of complex intervention for the rehabilitation of aphasia caused by cerebrovascular disease. RESULTS: More than 100 relevant articles were found. After analyzing these articles, we found that acupuncture for apoplectic aphasia most often included tongue, scalp, body and combination acupuncture. Tongue bleeding, deep insertion and strong stimulation were adopted by many practitioners. The ten most frequently used acupoints (or areas) were Lianquan (RN 23), Jinjin (EX-HN 12), Yuye (EX-HN 13), Tongli (HT 5), Fengchi (GB 20), Neiguan (PC 6), Baihui (DU 20), No. 1, 2 and 3 language sections, Sanyinjiao (SP 6) and Yamen (DU 15). CONCLUSIONS: Controlled clinical studies and a systematic literature review demonstrate that acupuncture has therapeutic effects on aphasia after stroke.

[Determination of lead in grape wine by graphite furnace atomic absorption spectrometry with ammonium dihydric phosphate as modifier].

Ammonium dihydric phosphate (NH4H2PO4), palladium chloride, nickelous nitrate and magnesium nitrate were used as modifiers respectively, to directly detect lead in grape wine with graphite furnace atomic absorption spectrometry(GFAAS). The results showed that NH4H2PO4 might be the best modifier. It was found that the organic matter in grape wine interfere with the determination. To remove the interference and detect lead directly with GFAAS, not only did samples need to be diluted with 4 to 10 times sample volumes of de-ionized water, but also the standard addition method was used. The method had good precision and accuracy when concentration of lead was above 10 micrograms.L-1, the relative standard deviations of lead were between -5.4% and 6.2%.