Effect of Xiangsha Liu Junzitang on Gastric Motility and CRF and UCN2 Expression in Rats with Functional Dyspepsia Due to Spleen Deficiency / 中国实验方剂学杂志

ObjectiveTo observe the effects of Xiangsha Liu Junzitang （XSLJZ） on gastric emptying rate and expression levels of corticotropin-releasing factor （CRF） and urocortin 2 （UCN2） in rats with functional dyspepsia （FD） due to spleen deficiency. MethodForty-eight 10-day-old male SD rats were randomly divided into the normal group （n=8） and iodoacetamide （IA） group （n=40）， and they separately received 2% sucrose solution and 0.1% sucrose solution containing IA for six successive days. Following the removal of mother rats， the three-week-old IA-treated rats were randomized into five groups， namely the model group， mosapride group， and low-， middle-， and high-dose XSLJZ groups， with eight rats in each group. At the age of six weeks， rats in all groups expert for the normal group were modeled by the modified multiple platform method for 14 d. Afterwards， the ones in normal group and model group were treated with 10 mL·kg-1 distilled water， and those in the treatment groups with 1.6×10-3 g·kg-1 mosapride and 2.8， 5.6， and 11.2 g·kg-1 XSLJZ by gavage， respectively， for 14 d. The grasping ability and gastric emptying rate were determined. The histological changes in gastric antrum were observed by hematoxylin-eosin （HE） staining. The protein and mRNA expression levels of CRF and UCN2 in gastric antrum were detected by Western blot and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. ResultNo obvious change or organic lesion was observed in gastric antrum of rats in each group. Compared with the normal group， the model group exhibited lowered gastric emptying rate and grasping ability （P<0.01）， up-regulated CRF protein and mRNA expression in gastric antrum （P<0.01）， and down-regulated UCN2 protein and mRNA expression （P<0.05， P<0.01）. Compared with the model group， XSLJZ at the middle and high doses enhanced the grasping ability and gastric emptying rate （P<0.05， P<0.01） and down-regulated CRF mRNA expression to varying degrees （P<0.05， P<0.01）. XSLJZ at the high dose decreased CRF protein expression （P<0.05） and up-regulated UCN2 protein and mRNA expression （P<0.01）. ConclusionThe mechanism of XSLJZ in invigorating spleen and promoting gastric motility of FD rats may be related to its reduction of CRF and elevation of UCN2 in gastric antrum.

Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism of Tojapride, a Chinese herbal formula extract, on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE).@*METHODS@#Ten out of 85 SD rats were randomly selected as the sham group (n10), and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model, low-, medium-, and high-dose of Tojapride as well as omeprazole groups (n10). Three doses of Tojapride [5.73, 11.46, 22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)] were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume, pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining, and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-KBp65), κB kinase beta (IKKß), occludin, and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot, respectively.@*RESULTS@#The gastric pH value in the model group was significantly lower than the sham group (P<0.05). Compared with the model group, gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (P<0.05). A large area of ulceration was found on the esophageal mucosa from the model rats, while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group, the IKKß levels were significantly higher in the model group (P<0.05). However, the IKKß levels were down-regulated after treatment by all doses of Tojapride (P<0.01 or P<0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (Ps0.01 or Ps0.05), while both indices were significantly up-regulated in the Tojapride-treated groups (P<0.01 or P<0.05).@*CONCLUSIONS@#Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKß expression and elevating ZO-1 and occludin expression, thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.

Mechanism of Traditional Chinese Medicine in Prevention and Treatment of Precancerous Lesions of Gastric Cancer： An Exploration Based on Gastric Microenvironment / 中国实验方剂学杂志

At present， the incidence and mortality of gastric cancer in China are 10.26% and 12.45%， ranking the second and third places， respectively， in the incidence and mortality of malignant tumors in China. Cancer often goes through three stages： precancerous lesions， carcinoma in situ， and invasive carcinoma. It is of great significance to advance cancer prevention and control to the stage of precancerous lesions. The popularization of digestive endoscopy-assisted diagnosis and treatment has enabled the timely diagnosis and treatment of early gastric cancer and severe dysplasia. However， the endoscopic mucosal resection is not suitable for most precancerous lesions of gastric cancer （PLGC）， and the effective drugs are not available. The long-term clinical dynamic monitoring has imposed considerable physical and mental burdens on patients. Gastrointestinal microenvironment is a dynamic balance system composed of gastrointestinal flora， chemical barrier， mechanical barrier， immune barrier， and gastrointestinal nerves. The imbalance of gastric microenvironment has been proved to be the key mechanism of PLGC. According to traditional Chinese medicine （TCM）， PLGC is a result of long-term interaction between deficient healthy Qi and excessive pathogens. In syndrome differentiation and treatment， PLGC is often believed to be developed from chronic gastritis. Besides， the inflammation-cancer transformation model put forward by Correa and the evolution of its TCM pathogenesis are also considered. Guided by the basic treatment principle of reinforcing healthy Qi to eliminate pathogenic factors， we determined the basic therapeutic methods as follows： invigorating spleen， clearing heat， and resolving dampness. At the same time， such methods as soothing liver and regulating Qi， resolving phlegm and dissipating mass， activating blood and resolving stasis， clearing heat and removing toxin， and tonifying deficiency can be combined based on the results of syndrome differentiation. After discussing the correlation between the imbalance of gastric microenvironment and PLGC and summarizing TCM intervention methods and mechanisms against PLGC from the perspective of gastric microenvironment regulation， this paper believed that TCM improved the gastric microenvironment by regulating the disorder of gastric flora， eliminating the gastric mucosal inflammation， and relieving the abnormal immune response， thereby preventing and controlling the PLGC.

Gegen Qinliantang Alleviates Ulcerative Colitis via Cell Signaling Pathways： A Review / 中国实验方剂学杂志

Gegen Qinliantang， a classic traditional Chinese medicine（TCM） compound， has been verified in modern research to possess various pharmacological effects such as anti-inflammation，anti-oxidative stress，protecting intestinal mucosal barrier， and regulating intestinal flora and immune response. Ulcerative colitis （UC） is a chronic idiopathic inflammatory disease involving the colorectal mucosa， which mainly results from genetic susceptibility， intestinal mucosal barrier damage， abnormal immune response， intestinal flora disturbance， and bile acid metabolism disorders. By reviewing the literature published in recent years， this paper sorted out the relevant pathways and mechanisms involved in the treatment of UC by Gegen Qinliantang to provide ideas for further clinical and basic research. This literature review uncovered that Gegen Qinliantang exerted the therapeutic effects against UC mainly via interleukin-6（IL-6）/Janus tyrosine kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3） signaling pathway， Toll like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB） signaling pathway，Notch signaling pathway， and matrix metalloproteinase-9（MMP-9）/p38 mitogen-activated protein kinase（p38 MAPK） signaling pathway. Gegen Qinliantang regulates the intercellular molecular transmission in multiple pathways to protect the intestinal mucosal barrier， adjust the immune response and anti-oxidative stress， and relieve UC， demonstrating the multi-target， multi-mechanism， and multi-pathway advantages of TCM compounds.

Chang'an II Decoction ( II )-Containing Serum Ameliorates Tumor Necrosis Factor-α-Induced Intestinal Epithelial Barrier Dysfunction via MLCK-MLC Signaling Pathway in Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Chang'an II Decoction ( II ))-containing serum on intestinal epithelial barrier dysfunction in rats.@*METHODS@#Tumor necrosis factor (TNF)-α-induced injury of Caco-2 monolayers were established as an inflammatory model of human intestinal epithelium. Caco-2 monolayers were treated with blank serum and Chang'an II Decoction-containing serum that obtained from the rats which were treated with distilled water and Chang'an II Decoction intragastrically at doses of 0.49, 0.98, 1.96 g/(kg·d) for 1 week, respectively. After preparation of containing serum, cells were divided into the normal group, the model group, the Chang'an II-H, M, and L groups (treated with 30 ng/mL TNF-α and medium plus 10% high, middle-, and low-doses Chang'an II serum, respectively). Epithelial barrier function was assessed by transepithelial electrical resistance (TER) and permeability of fluorescein isothiocyanate (FITC)-labeled dextran. Transmission electron microscopy was used to observe the ultrastructure of tight junctions (TJs). Immunofluorescence of zonula occludens-1 (ZO-1), claudin-1 and nuclear transcription factor-kappa p65 (NF-κ Bp65) were measured to determine the protein distribution. The mRNA expression of myosin light chain kinase (MLCK) was measured by real-time polymerase chain reaction. The expression levels of MLCK, myosin light chain (MLC) and p-MLC were determined by Western blot.@*RESULTS@#Chang'an II Decoction-containing serum significantly attenuated the TER and paracellular permeability induced by TNF-α. It alleviated TNF-α-induced morphological alterations in TJ proteins. The increases in MLCK mRNA and MLCK, MLC and p-MLC protein expressions induced by TNF-α were significantly inhibited in the Chang'an II-H group. Additionally, Chang'an II Decoction significantly attenuated translocation of NF-κ Bp65 into the nucleus.@*CONCLUSION@#High-dose Chang'an II-containing serum attenuates TNF-α-induced intestinal barrier dysfunction. The underlying mechanism may be involved in inhibiting the MLCK-MLC phosphorylation signaling pathway mediated by NF-κ Bp65.

Research Progress on Mechanism of Tongxie Yaofang in Treating Diarrhea-Predominate Irritable Bowel Syndrome Based on Brain-gut Interaction Function / 中国实验方剂学杂志

Diarrhea-predominant irritable bowel syndrome (IBS-D) is one of the common functional gastrointestinal diseases in clinical practice, its pathogenesis is diverse. Because of its sudden and lingering intractable symptoms, it seriously affects patients' work and life. IBS-D patients suffer from repeated illnesses, which often affect their lives with mental symptoms such as anxiety and depression. Anxiety and depression can also affect visceral sensation, increase intestinal sensitivity, aggravated by interaction between physical symptoms and mental symptoms. The main pathogenesis of IBS-D such as visceral hypersensitivity, gastrointestinal motility disorders, intestinal infections, and psychosocial factors are all related to brain-gut interaction disorders. Patients with IBS-D are prone to brain-gut interaction disorders due to long-term chronic mental stress. Brain-gut interaction is the main mode of regulation of gastrointestinal function in the brain-gut axis. Traditional Chinese medicine （TCM） believes that the main syndrome type of IBS-D patients is liver stagnation and spleen deficiency, while liver stagnation will be unsatisfactory, and the secretion and content of various neurotransmitters in the brain are closely related to emotions. Tongxie Yaofang is a commonly basic prescription used for the clinical treatment of IBS-D liver stagnation and spleen deficiency syndrome. It has the functions of softening the liver and replenishing the spleen, removing dampness and stopping diarrhea, and has a significant clinical effect. At present, many animal experiments and clinical studies have explored the mechanism of Tongxie Yaofang in treating IBS-D and its effect on brain-gut interaction function and brain-gut peptide content, but the main liver drainage and brain-gut interaction have not been linked. The author took the correlation between liver liver govers regulating and brain-gut interaction as the starting point, explored the mechanism of Tongxie Yaofang in treating IBS-D based on brain-gut interaction disorder, and explained the correlation between the three. Based on the research literature of Tongxie Yaofang in the past 5 years and the interaction between Tongxie Yaofang and brain-gut interaction, the author explored the effect of Tongxie Yaofang in treating IBS-D by affecting the brain-gut axis and brain-gut peptides.

Effect of Medicated Serum Prepared with Chang'an Ⅰ Prescription on Sensitized Mast Cell Degranulation / 中国实验方剂学杂志

Objective:To observe the influence of Chang'an Ⅰ prescription drug-containing serum on IgE-mediated RBL-2H3 cell degranulation model， and explore the mechanism of Chang'an Ⅰ prescription in inhibiting RBL-2H3 activation degranulation and releasing inflammatory mediators with v-yes-1 Yanaguchi sarcoma viral related oncogene homolog （Lyn）/spleen tyrosine protein kinase （Syk）/mitogen-activated protein kinase （MAPK） signal pathway. Method:Preparation for Chang'an Ⅰ prescription serum. Animal group， SD male rats were randomly divided into Chang'an Ⅰ prescription serum high， medium， low dose， and blank control groups with 10 rats in each group. Dosage： 10 mL·kg-1 distilled water was given to blank control group， while Chang'an Ⅰ prescription serum high， medium and low dose groups were respectively given to the Chang'an Ⅰ prescription concentrated crude drug with concentration of 1.15，2.30，4.60 g·kg-1， respectively once a day for 7 days continuously and then blood was taken from aorta ventralis and centrifuged. Ketotifen as the positive control drug. Mast cells are counted with toluidine blue staining. Cellular release of β-aminohexose was detected by colorimetric method. Contents of MCT， TNF-α， MCP-1 and histamine were measured by enzyme-linked immunosorbent assay （ELISA） kits， Lyn/Syk/MAPK protein levels were detected by immunoblotting. Result:For cell activation and degranulation， compared with the blank control group， the model group had more cell degranulation （P<0.05）， compared with model group， the cell degranulation rate of each dose group of Chang'an Ⅰ prescription decreased （P<0.05）. The release rate of β-hexosamine in each dose group of Chang'an Ⅰ prescription decreased significantly （P<0.01）. For the release of active mediators， compared with the blank control group， the contents of histamine， MCT， TNF-α and MCP-1 all increased in the model group （P<0.01）， compared with the model group， the contents in each dose group of Chang'an Ⅰ prescription all decreased significantly （P<0.01）. Compared with the normal group， the phosphorylation levels of Lyn and Syk， extracellular regulatory protein kinase 1/2（ERK1/2）， c-Jun N-terminal kinase （JNK）， and mitogen-activated protein kinase p38 increased in the model group （P<0.05）. Compared with the model group， the Lyn， Syk and ERK1/2， JNK and p38 protein phosphorylation levels reduced in Chang'an Ⅰ prescription group （P<0.05）. Conclusion:Chang'an Ⅰ prescription drug-containing serum down-regulates the phosphorylation levels of proteins Lyn， Syk， and ERK1/2， JNK， and p38， inhibits RBL-2H3 cell activation and degranulation， reduces the release of cytokines and chemokines， such as histamine， MCT， TNF-α and MCP-1， it may be one of its mechanisms for treating IBS-D visceral hypersensitivity.

Analysis on Medication Rules of National Medical Masters in Treatment of Stomachache / 中国实验方剂学杂志

Objective: To analyze medication rules of national medical masters in the treatment of stomachache by data mining. Method: Prescriptions were collected from 9 works as well as the first batch of national medical masters' medical cases and prescriptions for stomachache recorded in CNKI. Then, Microsoft Excel 2016 was adopted for analyzing the frequencies, properties, flavors and meridian tropisms of herbs, the Apriori algorithm provided by SPSS Clementine 12.0 software was used to analyze association rules of the herbs, and factor analysis was conducted by SPSS 19.0 software. Result: A total of 175 prescriptions containing 230 herbs were selected. The top five herbs used in frequency ranking were Glycyrrhizae Radix et Rhizoma, Paeoniae Radix Alba, Pinelliae Rhizoma, Atractylodis Macrocephalae Rhizoma, Poria. The medical properties with high usage frequency were warm, mild and slight cold. The flavors were sweet, bitter and pungent. Meridian tropisms were spleen, stomach and lung. Herbs for regulating Qi, tonifying Qi and promoting digestion ranked top three according to the classification of efficacy. The association rules analysis showed that the highest confidence and support of the related drugs was Atractylodis Macrocephalae Rhizoma→Codonopsis Radix-Poria, which reflected treatment characteristics of national medical masters with Sijunzitang as the basic prescription for tonifying Qi. A total of 12 strongly association rules of 2-drug pairs were obtained by association rules, and the most commonly used of which was Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma. Nine common factors were respectively extracted by factor analysis. Conclusion: Herbs used in the prescriptions of national medical masters for treatment of stomachache are often with the actions of regulating Qi, invigorating deficiency and benefiting Qi, in addition, Shaoyao Gancaotang is often used to generate Yin and relieve pain.

Design and Evaluation of Online/offline Interface Based on Double Loop for Two-dimensional Chromatography / 分析化学

By using a double loop technique based on a set of mechanical transmission components and a flow path system,a double function of injection and fraction collection was realized. On the basis of double loop technique,a novel type of online/offline interface for two-dimensional liquid chromatography was designed to construct an efficient separation system coupling two different separation modes with a higher peak capacity, and the functions of the interface were evaluated. By means of connecting the interface to an HPLC system, the multiple functions of injection, fraction collection and injection again were fulfilled for preparation and purity analysis of 4 kinds of aromatic compounds. As for combination of 2 sets of HPLC system,5 kinds of protein samples were separated preliminarily by strong cation exchange chromatography, and the components difficult to separate were collected and injected into reversed phase chromatographic system for further separation. Furthermore, the interface was applied to coupling two chromatographic systems in both strong cation exchange mode and microcolumn reversed-phase mode for the two-dimensional separation of bovine serum albumin enzymatic digest. When 1 mAU was set as the integral threshold,a total number of 292 peaks were identified. With the help of the online/offline interface, the preparation of microscale samples, fine separation of hardly separated samples and two-dimensional separation of complex samples were achieved flexibly. The result indicated that the system was a potent tool for the construction of two-dimensional chromatographic system and separation research.

Therapeutic Effect of Chang'an I Recipe ( I ) on Irritable Bowel Syndrome with Diarrhea: A Multicenter Randomized Double-Blind Placebo-Controlled Clinical Trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Chinese medicine (CM) decoction Chang'an I Recipe ( I ) in the treatment of irritable bowel syndrome with diarrhea (IBS-D).</p><p><b>METHOD</b>A multicenter, randomized, double-blind, placebo-controlled clinical trial was designed. Based on the order of inclusion, the IBS-D patients were randomly assigned to the treatment group or the placebo control group, administrated with Chang'an I Recipe or placebo, 150 mL/bag, 3 times daily, for 8 weeks. The primary indices of efficacy included the effective rates of IBS symptom severity score (IBS-SSS) and the differences in adequate relief (AR) responder; the secondary indexes of efficacy included the changes in scores of the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression (HAD) scales. The safety indices included adverse events and related laboratory tests.</p><p><b>RESULTS</b>A total of 216 patients were included, with 109 in the treatment group and 107 in the control group, and finally 206 were included in the full analysis set (FAS), 191 were included in the per protocol set (PPS). In FAS, the total effective rate was 67.6% and 40.2% for the treatment and control groups, respectively, with 95% confidence interval (CI) for difference in the effective rates between the two groups of 14.4%-40.2%; while in PPS, the total effective rate was 71.3% and 41.2% for the treatment and control groups, respectively (95% CI 16.6%-43.4%). The consistent conclusions of FAS and PPS showed a better efficacy in the treatment group. Both FAS and PPS showed higher AR responder in the treatment group (FAS: 59.6% vs. 35.5%; PPS: 62.8% vs. 38.1%). As for IBS-QOL, the total score and scores in various dimensions of IBS-QOL were not significantly different between the two groups (P>0.05). Both anxiety and depression scales of HAD were not significantly different between the two groups (P>0.05). No adverse events or laboratory abnormalities were found to be obviously related to the tested drugs or clinically significant.</p><p><b>CONCLUSION</b>Chang'an I Recipe was more effective than placebo in the treatment of IBS-D, with no obvious adverse reactions. (No.ChiCTR-TRC-09000328).</p>

A preparation model of Chinese medicine decoction placebo / 中国结合医学杂志

Chinese medicine (CM) decoction placebo is one of the key factors restricting the placebo-controlled clinical trial of CM. In this article, based on the analysis of the diffificulties in preparing CM placebo, the production requirements for placebo were put forward. Moreover, in accordance with clinical practices, a production method and evaluation process of CM decoction placebo was proposed, to provide a reference for clinical research.

Randomized double-blind clinical trial of Moluodan () for the treatment of chronic atrophic gastritis with dysplasia / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of Moluodan () in treating dysplasia in chronic atrophic gastritis (CAG) patients.</p><p><b>METHODS</b>This was a multi-centered, double-blind, randomized controlled trial. The total of 196 subjects were assigned to receive either Moluodan or folic acid in a 2:1 ratio by blocked randomization. Mucosa marking targeting biopsy (MTB) was used to insure the accuracy and consistency between baseline and after 6-month treatment. Primary outcomes were histological score, response rate of pathological lesions and dysplasia disappearance rate. Secondary endpoints included gastroscopic findings, clinical symptom and patient reported outcome (PRO) instrument.</p><p><b>RESULTS</b>Dysplasia score decreased in Moluodan group (P =0.002), significance was found between groups (P =0.045). Dysplasia disappearance rates were 24.6% and 15.2% in Moluodan and folic acid groups respectively, no significant differences were found (P =0.127). The response rate of atrophy and intestinal metaplasia were 34.6% and 23.0% in Moluodan group, 24.3% and 13.6% in folic acid group. Moluodan could improve erythema (P =0.044), and bile reflux (P =0.059), no significance between groups. Moluodan was better than folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite (P <0.05), with symptom disappearance rates of 37% to 83%.</p><p><b>CONCLUSIONS</b>Moluodan improved dysplasia score in histopathology, and erythema and bile reflux score in endoscopy, and superior to folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite. [ChiCTR-TRC-00000169].</p>

Effect of Chang'an No. I Recipe on 5-hydroxytryptamine Signal System and mRNA Expression Levels of Hippocampal Brain Derived Neurotrophic Factor in Visceral Hypersensitivity Rats with Irritable Bowel Syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Chang'an No. I Recipe (CA) on 5-hydroxytryptamine signal system and mRNA expression levels of hippocampal brain derived neurotrophic factor (BDNF) in visceral hypersensitivity model rats with irritable bowel syndrome (IBS).</p><p><b>METHODS</b>IBS visceral hypersensitivity rat models were established by combined chronic restraint stress and forced swimming. Successfully modeled rats were randomly divided into the model group, the Dicetelgroup (27 mg/kg) , the Fluoxetine group (3.6 mg/kg), the high dose CA group (22.6 mg/kg), the medium dose CA group (11.3 mg/kg), and the low dose CA group (5.7 mg/kg) according to body weight, 9 in each group. Besides, a normal control group with 10 rats was set up. Corresponding medication was administered to rats in each treatment group. Equal volume of physiological saline was administered to rats in the model group by gastrogavage. All medication was performed once per day for a total of 14 days. Pain threshold was determined by abdominal withdrawal reflex (AWR). Changes of colon 5-HT levels were determined by immunohistochemical assay. mRNA expression levels of hippocampal 5-hydroxytryptamine 1A receptor (5-HT1a) and BDNF were detected by immunofluorescent RT-PCR.</p><p><b>RESULTS</b>Compared with the normal control group before treatment, pain threshold was obviously lowered in proctectasia rats of each group (P < 0.01). Compared with the normal control group after treatment, pain threshold was obviously lowered in rats of the model group; colon 5-HT levels, mRNA expression levels of hippocampal 5-HT1a and BDNF were obviously elevated (P < 0.01). Compared with the model group, pain threshold was obviously elevated in the Fluoxetine group and all CA groups; colon 5-HT levels were obviously reduced in the Dicetel group, high and medium dose CA groups (P < 0.05, P < 0.01); mRNA expression levels of hippocampal 5-HT1a and BDNF were obviously reduced in each CA group (P < 0.01); mRNA expression levels of hippocampal BDNF were obviously reduced in the Fluoxetine group (P < 0.01).</p><p><b>CONCLUSIONS</b>The target points of CA were involved in brain and gut. CA could reduce pain threshold of proctectasia rats, down-regulate colon mucosal 5-HT levels, and lower mRNA expression levels of BDNF and 5-HT1a in rat hippocampus.</p>

Effect of ronggan mixture on immunoregulation and hepatocyte apoptosis-related factors in concanavalin A induced acute immunological liver injury mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Ronggan Mixture (RM) on immunoregulation and hepatocyte apoptosis-related factors in concanavalin A (Con A) induced acute immunological liver injury mice.</p><p><b>METHODS</b>Totally 60 hepatitis B virus (HBV) transgenic mice were randomly divided into 6 groups, i.e., the blank control group, the model group, the RM group, the Herba Artemisiae Scopariae (HAS) group, the Yinchenhao Decoction (YD) group, and the Bifendate group, 10 mice in each group. The acute immunological liver injury model was established by tail vein injection of ConA. Fourteen days before modeling, normal saline was administered to mice in the blank control group and the model group. RM, YD, HAS decoction, and Bifendate solution was respectively given to mice in the RM group, the YD group, the HAS group, and the Bifendate group. The medication was performed once daily. One h after the last gastrogavage, phosphate buffer solution (PBS) was injected to mice in the blank control group from the tail vein. Modeling was conducted by injecting Con A at 3 microg/g body weight from the tail vein. Mice were sacrificed 8 h after modeling. Blood or tissue samples were collected to detect lab indicators such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), tumor necrosis factor alpha (TNF-alpha), interferon gamma (INF-gamma), IL-4, IL-10, Fas, FasL, Bax, and bcl-2.</p><p><b>RESULTS</b>There was significant difference in all lab indicators between the normal group and the blank control group (P < 0.05, P < 0.01). Compared with the model group, ALT and AST levels were significantly lower in the RM group and the Bifendate group (P < 0.01); TBil significantly decreased in the RM group (P < 0.01). The expression level of TNF-alpha decreased in the RM group (P <0.05). The expression level of IFN-gamma decreased in the RM group and the YD group (P < 0.05). The expression level of IL-4 could be elevated in all medicated groups (P < 0.05). RM could elevate the expression level of IL-10 (P < 0.05). The expression level of Fas in the liver tissue decreased in the RM group and the YD group (P < 0.05). The expression level of FasL decreased and the expression of bcl-2 gene increased in the RM group (both P < 0.05). The expression level of Bax was down-regulated in the RM group and the YD group (P < 0.05). The ratio of bcl-2/Bax was up-regulated in the RM group (P < 0.05). Meanwhile, RM showed better effect in decreasing expressions of ALT and AST than HAS (P < 0.05). The effect of increasing IL-10 expression levels was better in the RM group than in the YD group (P < 0.01). The effect of decreasing expressions of Fas and FasL was better in the RM group than in the HAS group, the YD group, and the Bifendate group (P < 0.05). The effect of enhancing the expression of IL-10 in the liver tissue was better in the RM group than in the HAS group (P < 0. 05).</p><p><b>CONCLUSION</b>RM had protective effect on Con A induced acute immunological liver injury mice, which might be achieved by changing the immunological balance of Thl/Th2 factors (decreasing expressions of TNF-alpha and IFN-gamma, elevating expressions of IL-10 and IL-4) and regulating hepatocyte apoptosis-related factors (down-regulating gene expressions of Fas, FasL, and Bax; up-regulating bcl-2 gene expression, and up-regulating the bcl-2/Bax ratio).</p>

Preliminary study of establishing and assessing IBS-D model rats of gan stagnation and Pi deficiency syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To establish a new disease-syndrome-symptom integrated diarrhea-predominant irritable bowel syndrome (IBS-D) rat model of Gan stagnation and Pi deficiency syndrome (GSPDS).</p><p><b>METHODS</b>(1) The model establishment method: We combined mother-infant separation, chronic restraint, and senna gavage to establish a new IBS-D model of GSPDS. Totally 48 experimental rats were divided into the normal group (Group A), the mother-infant separation group (Group B), the chronic restraint group (Group C), and the senna gavage group (Group D), the mother-infant separation + senna gavage group (Group E), and the mother-infant separation + chronic restraint + senna gavage group (Group F), 8 in each group. (2) The model evaluation method: We used pain threshold indicating colorectal distension to represent for the visceral sensitivity, thus evaluating the establishment of "disease" model; open field test and serum D-xylose levels to evaluate the establishment of GSPDS model; defecation numbers of grain and loose stool rate to evaluate the establishment of diarrhea symptom.</p><p><b>RESULTS</b>(1) Compared with Group A, the body weight gained less in Group F, showing statistical difference (P < 0.05). (2) The pain threshold significantly decreased in Group F, showing statistical difference when compared with Group A (P < 0.05). (3) Compared with Group A, the total cross number, the standing number, and the decoration number in Group F significantly decreased (P < 0.05). (4) Compared with Group A, the serum D-xylose level of Group F significantly decreased (P < 0.05). (5) Compared with Group A, the defecation numbers of grain and the loose stool rate significantly increased, showing statistical difference (P < 0.05).</p><p><b>CONCLUSIONS</b>A new disease-syndrome-symptom integrated IBS-D animal model of GSPDS successfully established might be a better animal model used for studying IBS by Chinese medicine. However, further studies are needed.</p>

Treatment of irritable bowel syndrome by Chinese medicine and pharmacy: an analysis of data mining on experiences of experts / 中国中西医结合杂志

<p><b>OBJECTIVE</b>The pathogenesis of irritable bowel syndrome (IBS), a functional gastrointestinal disorder, is poorly understood. Treatment by Chinese medicine and pharmacy (CMP) is superior to treatment by Western medicine (WM). Therefore, we aimed to analyze Chinese medical experts' experiences in treating IBS by data mining.</p><p><b>METHODS</b>By retrieving related literatures from 1994 to 2012 from CNKI, we chose proved cases and screened effective medical records to establish a database using structural electronic medical case collecting system and data mining. The thinking ways of modern physicians in diagnosis and treatment of IBS were analyzed.</p><p><b>RESULTS</b>Totally 116 medical cases from 46 Chinese medical experts were recruited and analyzed. Results showed that Gan depression and Pi deficiency were most basic syndrome elements. In addition, cold dampness, damp heat, yang deficiency, and Shen deficiency were main elements for the development of diarrhea predominant IBS (IBS-D). Qi stagnation, yin deficiency, qi deficiency, and blood stasis were main elements for the development of constipation predominant IBS (IBS-C). Soothing Gan-qi and strengthening Pi was the most important treatment method. White peony root, prepared atractylodes, prepared licorice, tangerine peel, poria, bupleurum, Radix sileris, lanceolata, and Radix aucklandiae were the most common Chinese herbs used in treating IBS.</p><p><b>CONCLUSIONS</b>(1) Gan depression and Pi deficiency was the main pathogenesis for IBS. Diagnosis and treatment of IBS should be performed clinically according to its development. Tongxie Yao-fang should be used as the basic prescription with modification according to syndrome differentiation. (2) Data mining will have a wide application prospect in studying medical cases.</p>

A randomized, controlled, double-blinded and double-dummy trial of the effect of tongjiang granule on the nonerosive reflux disease of and Gan-Wei incoordination syndrome / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the effectiveness of tongjiang granule (TJG) on the patients with nonerosive reflux disease (NERD) of Gan-Wei incoordination syndrome, its impact on their quality of life, and its safety.</p><p><b>METHOD</b>A randomized, controlled, double-blinded, and double-dummy method was adopted in the trial. There were 120 NERD patients enrolled in the study and randomly divided into the experiment and control groups, each with 60 patients; drugs were distributed according to the drug number by patients' inclusion sequences. In the experiment group, patients were given TJG 10 g and mosapride citrate dummy 5 mg three times a day, and in the control group, patients were given mosapride citrate 5 mg and TJG dummy 10 g three times a day. The treatment courses of both groups were 4 weeks.</p><p><b>RESULTS</b>Among 120 included patients, 112 were screened for full analysis set (FAS), and 105 were screened per-protocol set (PPS). The results were as follows: (1) the improvement of total scores of symptom in the experiment group (0-4 week) were 15.93±7.88 scores by FAS and 16.22 ±7.75 scores by PPS, and they were 10.43±10.16 scores and 10.79±10.27 scores in the control group, respectively. The 95% CI of net scores improvement between the two groups were 2.10-8.90 scores and 1.92-8.94 scores in FAS and PPS; it was significantly better in the experiment group than that in the control group (P<0.05). (2) The improvement of scores of major symptom in the experiment group (0-4 week) were 10.68±5.35 by FAS and 10.89±5.29 by PPS and 7.40±7.41 and 7.60±7.46 in the control group, respectively. The 95% CI of net scores improvement in the two groups were 0.85-5.71 and 0.71-5.69 in FAS and PPS separately, and the improvement in the experiment group was significantly better than that in the control group (P<0.05). (3) The total effective rates were 86.0% and 61.8% in the experiment and the control group separately, and the Ridit analysis results showed that it was better in the experiment group (P<0.05). (4) The improvement quality of life in the domain of physical functioning and general health in the experiment group was better than that in the control group (P<0.05). (5) One case of experiment group caught a cold and recovered in six days without drug suspension. No adverse event was found in the other cases. There was no meaningful safety examination indices change in pretreatment and posttreatment periods in both groups.</p><p><b>CONCLUSION</b>TJG showed a definite effect on the treatment of NERD with Gan-Wei incoordination syndrome, and it could improve the quality of life of NERD patient without obvious toxic and side effects.</p>

Pathological changes of the cornea in rabbits with hyphema and concurrent ocular hypertension / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the impact of hyphema secondary to high intraocular pressure on corneal pathology in rabbits.</p><p><b>METHODS</b>Thirty adult New Zealand rabbit were randomized into 3 equal groups, and in each rabbit, one eye served as the experimental eye with the other as the control eye. In the experimental eye, autoblood was injected into the anterior chamber to induce high intraocular pressure maintained for 3, 5, or 8 days. Only saline was injected into the control eye. After the injections, the cornea was observed with slit-lamp microscopy, and at 3, 5, or 8 days, the experimental and control eyes were taken from the 3 groups for microscopic examination of the corneas to detect the occurrence of cornea bloodstain with prolonged high intraocular pressure. Corneal edema, elastic fibers changes, growth of new blood vessels, changes of eosinophils, fibroblasts, lymphocytes and plasma cells, as well as the pathological changes of the corneal layers were observed and compared between the experimental and control eyes.</p><p><b>RESULTS</b>Maintenance of high intraocular pressure for 8 days resulted in the most severe corneal edema and thickening, and histopathologically, the corneal stroma showed widened space between the elastic fibers and obvious fiber distortion. Neovascularization was seen in the marginal cornea where eosinophil infiltration occurred with a small number of lymphocytes, plasma cells and fiber cells. All the three groups showed more obvious edema in the posterior than in the anterior cornea.</p><p><b>CONCLUSION</b>Prolonged hyphema with ocular hypertension results in aggravation of corneal edema, and corneal blood staining does not occur until 8 days of high intraocular pressure but corneal elastic fiber disruption can be seen, suggesting the impending irreversible pathological changes of cornea.</p>

Effect of ronggan mixture on cell apoptosis in rats with chronic immune liver injury induced by concanavalin A / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effects of Ronggan Mixture (RGM) on cell apoptosis by observing the expressions of apoptosis-related genes (Fasl and Bcl-2) in transgenic mice with chronic liver immune injury induced by concanavalin A (ConA).</p><p><b>METHODS</b>Seventy-four transgenic mice were divided into 6 groups, the model group, the normal group, and the treated groups treated respectively with biphenyldicarboxylate (DDB), oriental wormwood (OWW), Yinchenhao Decoction (YCHD) and RGM. Pathologic changes of liver tissue were observed by light microscopy, number of apoptotic cells were determined by TUNEL method, and expressions of apoptosis-related genes, Fasl and Bcl-2, in hepatic T lymphocyte were detected by flow cytometer.</p><p><b>RESULTS</b>Evident pathological changes of liver appeared in the model mice, showed severely destroyed structure of hepatic lobules. As compared with the model group, the changes of liver fibrosis and cell necrosis were much lessened in the RGM group and the YCHD group (P < 0.05). The protein expression of apoptotic gene Fasl and the apoptotic index in the model group were higher than those in the normal group (P < 0.05), but that of the apoptotic inhibiting gene, Bcl-2, in model mice was similar to that in normal mice. As compared with the model group, apoptosis index decreased (P < 0.01), levels of Fasl expression was lower and Bcl-2 expression was higher in the RGM group and the YCHD group (P < 0.05, P < 0.01), and the effect of the two was similar, but significantly superior to that of OWW and DDB (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>The Chinese compound, RGM and YCHD can not only relieve the hepatic pathological injury, but also reduce the cell apoptosis in chronic liver immune injury mice through regulating the expressions of Fasl and Bcl-2.</p>

Study on genetic approach in the detection of Cryptosporidium parvum and Giardia lamblia in acquired immunodeficiency syndrome patients / 中华流行病学杂志

<p><b>OBJECTIVE</b>To establish genetic method in detecting Cryptosporidium parvum and Giardia lamblia which often coinfected with AIDS patients.</p><p><b>METHODS</b>Cryptosporidium oocysts and Giardia cysts were isolated and purified from fecal samples of the individuals infected with C. parvum and G. lamblia, respectively. Genomic DNAs were extracted. Two pairs of specific primers were designed or synthesized according to the 18S rRNA gene from C. parvum or the triose phosphate isomerase (tim ) gene from G. lamblia. Polymerase chain reaction(PCR) technique was used to amplify the DNA samples from the oocysts and the cysts, and those from the 6 control samples, including Schitosoma japonicum, Toxoplasma gondii , Entamoeba histolytica, Trichinella spiralis, Trichomonas vaginalis and human blood cells. DNA samples from 30 fecal samples of AIDS patients were detected with the same method.</p><p><b>RESULTS</b>One fragment of 500 bp was amplified with the primer of C. parvum, and the other one of 683 bp was amplified with the primer of G. lamblia. Twenty pg and 0.4 pg DNA of C. parvum and G. lamblia could be detected separately. The specificity of these two pairs of PCR primers was confirmed by the failure in the amplification of the control DNA samples. Out of 30 cases of AIDS patients, 7 showed C. parvum positive, while non Giardia was detected.</p><p><b>CONCLUSION</b>Genetic detection method for C. parvum and G. lamblia detection was established which was more sensitive and specific.</p>