Chang'an decoction alleviates endoplasmic reticulum stress by regulating mitofusin 2 to improve colitis.

OBJECTIVE: To evaluate the protective effects of Chang'an decoction (, CAD) on colitis, and investigate the potential mechanisms underlying these effects from the perspectives of endoplasmic reticulum (ER) stress induced by mitofusin 2 (MFN2). METHODS: The composition of CAD was identified by liquid chromatography-mass spectrometry technology. A mice model of dextran sulfate sodium (DSS) induced colitis was established and therapeutic effects of CAD were determined by detecting body weight, disease activity index, colon length and histopathological changes. Then, the expression levels of MFN2, ER stress markers and Nucleotide-binding domain and leucine-rich repeat protein3 (NLRP3) relevant proteins were detected by polymerase chain reaction (PCR), Western blot, immunohistochemistry and immunofluorescence staining. Subsequently, knockdown and overexpression cell model were constructed to further investigate the underlying mechanism of MFN2 mediating ER stress and energy metabolism by PCR, Western blot, electron microscopy and reactive oxygen species (ROS) staining. Finally, inflammatory indicator and tight junction proteins were measured by PCR and immunofluorescence staining to evaluate the protective effects of CAD. RESULTS: Results showed that the indispensable regulatory role of MFN2 in mediating ER stress and mitochondrial damage was involved in the protective effects of CAD on colitis in mice fed with DSS. Network pharmacology analysis also revealed CAD may play a protective effect on colitis by affecting mitochondrial function. In addition, our data also suggested a causative role for MFN2 in the development of inflammatory responses and energy metabolic alterations by constructing a knockdown and overexpression cell model whereby alter proper ER-mitochondria interaction in Caco-2 cells. Furthermore, relative expression analyses of ER stress markers and NLRP3 inflammasome showed the onset of ER stress and activation of NLRP3 inflammasome, which is consistent with the above findings. In contrast, intervention of CAD could improve the mucosal barrier integrity and colonic inflammatory response effectively through inhibiting ER stress response mediated by MFN2. CONCLUSION: CAD could alleviate ER stress by regulating MFN2 to exert therapeutic effects on DSS-induced colitis, which might provide an effective natural therapeutic approach for the treatment of ulcerative colitis.

Efficacy of active ingredients in Qingdai on ulcerative colitis: a network pharmacology-based evaluation.

OBJECTIVE: To elucidate the protective effect of Qingdai (, QD) on ulcerative colitis (UC) by means of and approaches. METHODS: A systems pharmacology analysis was per-formed to predict the active components of QD whereas the putative biological targets of QD against UC were obtained through target fishing, network cons-truction and enrichment analyses. Meanwhile, we examined the ameliorative effect of QD in a mouse model of dextran sulfate sodium (DSS)-induced colitis. During the 10-day experiment, the control and diseased mice were given with oral gavages of QD (1.3 g raw herbs·kg·d) or 5-aminosalicylic acid (5-ASA, 100 mg·kg·d) every day. The underlying pharma-cological mechanisms of QD in UC were determined using polymerase chain reaction tests, histological staining, enzyme-linked immunoassays, and Western blotting analysis. RESULTS: Searching from various network pharmacology databases, 29 compounds were identified in QD. According to the screening criteria suggested by TCMSP (i.e. OB ≥ 30% and DL ≥ 0.18), nine of them were considered the active ingredients that contribute to the ameliorative effects of QD on different mouse models of colitis. Most importantly, the protective effect of QD on DSS-induced colitis was significantly associated with modulations of the expression levels of glycogen synthase kinase 3-ß (Gsk3-ß) and forkhead box p3 (Foxp3), which are widely considered as important regulators of excessive inflammatory responses. CONCLUSIONS: The results of this study provide solid scientific evidence for the use of QD or its core active components in the clinical management of UC.

Research progress on animal models for the evaluation of diarrhea-predominant irritable bowel syndrome / 中国实验动物学报

Irritable bowel syndrome(IBS)is one of the most common functional gastrointestinal disorders,of which diarrhea-predominant IBS(IBS-D)accounts for the largest proportion.The pathogenesis of IBS-D is complicated and diverse,and there is currently a lack of clinically effective drugs.The establishment of animal models is an essential tool for further studies of the disease mechanisms,evaluation of clinical efficacy,and drug development,and the preparation and evaluation standards of models are important factors affecting the quality of the research.Based on the currently accepted pathogenesis of IBS-D and the previous modeling experience of our research group,this review systematically summarizes the evaluation method used in animal models of IBS-D in terms of diarrhea observation,visceral sensitivity tests,and intestinal motility tests,to provide a reference for future studies.

Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against metabolic dysfunction-associated steatotic liver disease

Background/Aims@#Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD. @*Methods@#Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. @*Results@#In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression. @*Conclusions@#Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

Analysis of the Formulation Regularity for Chinese Patent Medicines Containing Paeonia lactiflora Based on Data Mining / 中国药房

OBJECTIVE： To analyze the formulation regularity of Chinese patent medicines containing Paeonia lactiflora， and to provide evidence for modern clinical application and R&D of P. lactiflora. METHODS： The formulations of Chinese patent medicine containing P. lactiflora were collected from Chinese Materia Medica Preparation and 2015 edition of Chinese Pharmacopeia. Statistical analysis was performed on the frequency of medicinal material， channel tropism， distribution of attending syndromes and attending diseases， core medicine combination （support degrees were set as 10％， 20％， 30％ and confidence degree was 0.9） by using data mining methods such as descriptive statistics and association rule analysis in TCM Inheritance System V 2.5； the formulation regularity of common attending syndromes and attending diseases （support degrees were set as 20％， 30％， 40％ and confidence degree was 0.9） was analyzed. RESULTS： A total of 600 Chinese patent medicine formulations contained P. lactiflora， involving 673 ingredients. The main medicinal properties in Chinese patent medicines containing P. lactiflora were warm， followed by cold and neutral. The main medicinal flavor was sweet， followed by bitter and pungent. The main channel tropism was spleen， liver and heart channel. There were 165 kinds of main treatment diseases （menstrual disorder， dysmenorrhea， dizziness） and 159 main treatment syndromes （insufficiency of qi and blood， qi stagnation and blood stasis， liver and kidney deficiency）. Under the condition of 30％ support degree and 0.9 confidence degree， there were 20 core combination of Chinese patent medicine formulations containing P. lactiflora （Glycyrrhiza uralensis-P. lactiflora， Angelica sinensis-P. lactiflora， P. lactiflora-Poria cocos） and 19 association rules among drugs. Under the condition of 40％ support degree and 0.9 confidence degree， there were 8 core medicines in Chinese patent medicines containing P. lactiflora for menstrual disorders （such as P. lactiflora， Cyperus rotundus， A. sinensis）， 9 core medicines for dizziness （such as P. lactiflora， Rehmannia glutinosa， A. sinensis）， 9 core medicines for qi and blood deficiency （such as P. lactiflora， Atractylodes macrocephala， P. cocos）， and 10 core medicines for qi stagnation and blood stasis syndrome （such as P. lactiflora， Aucklandia lappa， G. uralensis）. CONCLUSIONS： In this study， data mining was used to analysis the main symptoms， compatibility characteristics and formulation rules of Chinese patent medicines containing P. lactiflora， which can provide a basis for the modern clinical application and new drug development of P. lactiflora.

MicroRNA-200a Targets Cannabinoid Receptor 1 and Serotonin Transporter to Increase Visceral Hyperalgesia in Diarrhea-predominant Irritable Bowel Syndrome Rats

BACKGROUND/AIMS: MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. METHODS: We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. RESULTS: The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. CONCLUSIONS: This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

Meta-analysis of Shenling Baizhu Powder Combined with Western Medicine in Treating Ulcerative Colitis / 广州中医药大学学报

Objective To make a Meta-analysis of the effectiveness and safety of Shenling Baizhu Powder (SBP) for the treatment of ulcerative colitis(UC),thus to provide evidence for the clinical treatment of ulcerative colitis.Methods Randomized controlled trials (RCTs) of SBP combined with western medicine vs western medicine in treating ulcerative colitis were included.The quality of RCTs was assessed by the Cochrane scale.A Meta-analysis was performed for the clinical efficacy,improvement of disease activity index (DAI) levels of the included trials.Results A total of 19 RCTs were included,involving 1498 cases.The results of Metaanalysis showed that compared with the western medicine group,the combined risk ratio(RR) of clinical efficacy in the SBP combined group was 1.55,95％ confidence interval (CI) being (1.39,1.72).The subgroup analysis based on control medicine showed that the combined RR of combined use of sulfasalazine or mesalazine/Olsalazine was 1.46,1.59 [95％CI (1.19,1.77) vs 95％CI (1.40,1.80)].The subgroup analysis based on different treatment courses showed that the combined RR of 1-30 days,31-60 days,61-90 days was 1.42,1.69,1.47 [95％CI (1.18,1.70) vs 95％CI (1.44,1.97) vs 95％CI (1.15,1.88)] respectively.The differences were significant (P ＜ 0.05).(2) The differences of the two groups on the improvement of DAI and inflammatory factors levels of interlekin-17(IL-17),IL-23,tumor necrosis factor alpha(TNF-α),C-reactive protein(CRP) were statistically significant(P ＜ 0.05).(3)The sensitivity analysis of the primary outcomes showed a higher homogeneity in the literatures and the funnel plot analysis showed no evidence of publication bias.Conclusion Compared with western medicine,SBP combined with western medicine has better clinical efficacy for the treatment of UC,and the combined use of mesalazine/Olsalazine medicated for 30-60 days is more effective on improving DAI and inflammatory factors levels.However,for the low quality of the included literatures and insufficient experimental design,the conclusion needs more evidence from large sample-size randomized double-blind controlled trials.

Clinical features of 35 patients with myasthenia gravis associated with other autoimmune diseases / 中国神经精神疾病杂志

Objective To analyze the clinical features of 35 patients with myasthenia gravis (MG) associated with other autoimmune diseases (ADMG). Methods One hundred seventy MG patients were divided into 2 groups. One group included MG patients with autoimmune diseases ( n=35), and the other included MG patients without auto?immune diseases (NADMG, n=135). Clinical features such as gender, age of onset, types of MG, myasthenic crisis, thy?mus abnormalities, different therapies, ocular MG progressing to general MG, and relapse of MG within one year were compared between ADMG and NADMG. Results 85.7%ADMG patients were female which was higher compared with NADMG (P< 0.001); median age of onset was 40 years old (23~45 years old) in ADMG group which was younger than NADMG group. Ocular MG and thymic hyperplasia were more frequent in ADMG group than in NADMG group (45.7%vs. 24.4%, P=0.013;14.3%vs. 1.5%,P=0.001,respectively). Other clinical features such as myasthenic crisis, thymoma, different therapies, ocular MG progressing to general MG, and relapse of MG within one year were not signifi?cantly different between the two groups. In multivariate analysis, female (OR=4.76, 95% CI:1.64-13.77; P= 0.004), age of onset (OR=0.96, 95%CI:0.92-0.99;P=0.019), ocular MG (OR=3.10, 95%CI:1.30-7.41;P=0.011) and thy? mic hyperplasia(OR=16.26, 95%CI:2.22-119.11;P=0.006) were significantly different between the two groups. Con?clusions ADMG is more common in female patients with ocular MG and thymic hyperplasia.

Development of Scale of Assessing Curative Effect of Traditional Chinese Medicine for Liver Disease / 广州中医药大学学报

Objective To develop a scale for evaluating the curative effect of traditional Chinese medicine (TCM) for liver disease under the guidance of the theory of TCM, and to improve the TCM efficacy evaluation standard system for liver disease. Methods According to the TCM theory, the concept model of the liver disease-specific scale was built in combination with the international connotation of QOL and patient-reported outcomes ( PRO). A primary clinical scale was established after item pool screening, field test, culture adaptation and clinical pre-survey by the research staff. Finally, 200 questionnaires were distributed and 198 questionnaires were reclaimed. Statistical analysis was conducted to choose the items. Results All the selected items were analyzed by the different statistical methods, including significance grading, discrete tendency ( coefficient of variation ) method, stepwise regression analysis, discriminatory analysis, Cronbach’s al pha, and principal component analysis and factor analysis. A self-reported subjective scale and a perceived objective scale were developed, including 17 self-reported subjective items and 13 objective items. Conclusion According to the TCM theory and the international connotation of QOL, the scale of assessing curative effect of TCM for liver disease is practical and repeatable. It will be worthy of further evaluation and promotion to clinical application.

Literature review and analysis of the development of health outcomes assessment instruments in Chinese medicine / 中西医结合学报

To evaluate the development of health outcomes assessment instruments in Chinese medicine.

Literature review and analysis of the application of health outcome assessment instruments in Chinese medicine / 中西医结合学报

To evaluate the application of health assessment instruments in Chinese medicine.

Effect of Baitouweng Decoction on intestinal miR-19a expression in mice with ulcerative colitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the therapeutic effect of Baitouweng Decoction on dextran sodium sulphate (DSS)-induced ulcerative colitis in mice and explore its mechanism involving miR-19a.</p><p><b>METHODS</b>Forty female c57 mice were randomly allocated into 4 equal groups, namely the normal control group, model group (treated with 3.5% DSS solution), treatment group (treated with DSS+Baitouweng Decoction), and positive control group (treated with DSS+5-ASA). Ulcerative colitis was induced in the mice by feeding them with 3.5% DSS in drinking water, and the mice in the control group were given water only. The disease activity index (DAI) of the mice in each group was recorded daily. Seven days later, the mice were sacrificed for histological examination of the intestines using HE staining; the expression of miR-19a mRNA in the intestines was detected using RT-qPCR.</p><p><b>RESULTS</b>Compared with the control group, the model group showed significantly increased DAI and histological scores, and administration of Baitouweng Decoction significantly lowered the DAI and histological scores of the DSS-treated mice. The expression of miR-19a was lowered following DSS treatment, and Baitouweng Decoction treatment caused an increased miR-19a expression in DSS-treated mice.</p><p><b>CONCLUSION</b>Baitouweng Decoction has therapeutic effects on DSS-induced ulcerative colitis in mice, and this effect is probably mediated by enhancement of miR-19a expression in the intestines.</p>

On the necessity of developing quality of life instruments in traditional Chinese medicine / 中西医结合学报

The development of health-related quality of life (HRQL) instrument in traditional Chinese medicine (TCM) is increasing rapidly in China, but few studies focus on their necessity. This study explores the necessity of the development of TCM instruments from both theoretical and practice perspectives, and aims to explain whether the adoption of the cross-medical style is valid. Through theoretical analysis, both TCM and Western medicine instruments show the same objectives, whereas TCM instruments are more suitable for the Chinese social behavior, customs and expectations. In practical analysis, 47 TCM instruments were identified, among which 17 had 18 corresponding Western medical instruments. In the domains layer, except for physiological, psychological and social factors, TCM instruments focus more on the harmony between body and spirit, humanity and nature or human and society and the constitution, etc. In the facts layer, TCM instruments focus on the emotions, initiative social intercourse, TCM symptoms, diet, sleep, taste, feces and urine, etc. In addition, significant differences existed in the methods of information selection. There is no need to modify cross-medical style research except when TCM characteristic terms exist, but attention must be paid to the influence of culture in different areas. Therefore, the TCM instruments can resolve the limitations of the application of Western medical instruments to the Chinese setting, while also having remarkable abilities of information coverage and detection. Both forms of instruments have the capacity and requirement to inter-communicate with each other in order to serve the whole Chinese cultural system. Generally speaking, there is no need to modify the instruments in cross-medical style research. But this point requires further demonstration in the rigorous designed clinical trials.

Biological property and clinical application of tissue engineered skin / 中国组织工程研究

BACKGROUND:Tissue engineered skin has been used to repair defect skin, but it is not as good as to completely replace permanent skin. OBJECTIVE: To explore the biological characteristics and clinical application of various types of tissue engineered skin. METHODS: Pubmed data (1990-01/2005-12) was retrieved by computer with the key words of "tissue-engineered skin". CNKI database (2002-01/2007-12) was retrieved with the same key words. RESULTS AND CONCLUSION: Totally 226 literatures were primarily selected. After reading titles and Abstracts, studies addressing irrelative objective or repetitive content were excluded, and 11 literatures were included. The aim of skin tissue engineering is to create skin substitute that close to human.skin in histology and functional characteristics. There were many mature tissue engineered skin in clinic, and various artificial skins were developed. Their structure was similar to human, but only had skin barrier function and lack of skin appendages, so they did not have complete skin function, and did not reach skin reestablishment. Ideal skin substitute should process cuticular layer and dermial layer. The dermial layer can reach rapid vascularization and nerve redistribution, can promote physiological wound repair. The cuticular layer can rapidly obtain full barrier and protection function, which can be fully integration with wound surface. A good dermial carrier has good histocompatibility, and a certain physical and chemical properties, such as strength, scratchability, elasticity, gas permeation, water vapor permeability. These can provide a good adherence between dermis and wound surface, offer an ideal fiber stent for cell growth, and finally promote autologous skin growth. Tissue engineered skin has good prospect, but there are many problems that should be solved in biocompatibility and skin function reestablishment.

Development of patient-reported outcome scale for myasthenia gravis: a psychometric test / 中西医结合学报

To investigate the scientificity of patient-reported outcome (PRO) scale for myasthenia gravis (MG), which was used to evaluate the clinical effects of traditional Chinese and Western medicine treatment on MG patients. Psychometric performance of the MG-PRO scale was also expected to be evaluated in this study.

Effects of hypoxic training of skeletal muscle structure and function / 中国组织工程研究

BACKGROUND: Hypoxic training in combined with exercise training can increase the hypoxia levels of the body to mobilize the potentials of the body, resist to and actively adapt physiological responses resulted from hypoxia, so as to improve athletic performance.OBJECTIVE: To summarize the influence of hypoxic training on skeletal muscle structure and function, to provide a theoretical basis and guidance for hypoxic training.METHODS: Using "hypoxic training, skeletal muscle, function, structure" in English as the search terms, PubMed database was ratrieved from 1990 to March 2009; Using "hypoxic training, skeletal muscle, function and structure" in Chinese as the search terms,CNKI database was searched from 2000 to May 2009. Literatures are limited to English and Chinese languages. The content related to the effect of hypoxic training on skeletal muscle structure and function was selected, and repetitive researches were eliminated.RESULTS AND CONCLUSION: Totally 144 literatures were obtained from computer screening, and then analyzed according to the inclusion and exclusion criteria. Hypoxic training could avoid the disadvantages caused by conventional altitude training, the hypoxia environment is regulated according to the body's ability to adapt hypoxia, the normal training is ensured, so that skeletal muscle obtains beneficial physiological adaptation. Compared with pure hypoxia stimulation, different forms of hypoxia and different training methods may integrate into different modes of hypoxic training, which makes skeletal muscle function and structure more complex. The combination form of hypoxia and training is the main factor of the effect of hypoxia training on skeletal muscle function and structure. Different objects of experiments and test methods are likely to interfere with the conclusions, which also affect the mechanism of the role of hypoxic training on skeletal muscle.

Application of factor analysis in development and validation of a new questionnaire for quality of life / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the application of factor analysis in creating a new health-related questionnaire for evaluating quality of life, the Chinese for Quality of Life Instrument (ChQOL).</p><p><b>METHODS</b>Two hundred and seventy-three subjects selected from two provinces of North China (Ningxia) and South China (Guangdong) were investigated by ChQOL, and the preliminary version was completed with factor analysis.</p><p><b>RESULTS</b>Fifty items were developed using factor analysis. The final structure model of ChQOL was confirmed through the screening and verification of factor structural model on the 78 items of ChQOL, a new questionnaire with more rational structure was confirmed.</p><p><b>CONCLUSION</b>Factor analysis is an effective method in developing new questionnaire.</p>

Establishment of the Scale of the Quality of Life for Ankylosing Spondylitis / 广州中医药大学学报

[Objective] To establish the scale of the quality of life for patients with ankylosing spondylitis. [Methods] Initial scale including 58 items was proposed by the research staff. After the preliminary test was performed, 37 items were selected and a confirmed scale of the quality of life for ankylosing spondylitis ( SQOL-AS) was obtained. The feasibility, reliability, validity and sensitivity of SQOL-AS were analyzed. [Results] Statistics showed that SQOL-AS had a good feasibility, reliability, validity and sensitivity. [Conclusion] SQOL-AS can be used to evaluate the quality of life for patients with ankylosing spondylitis.