Clinical Efficacy of Modified Banxia Xiexintang Combined with Vedolizumab in Treatment of Crohn's Disease with Syndrome of Cold and Heat in Complexity / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy of modified Banxia Xiexintang combined with vedolizumab （VDZ） in the treatment of active moderate to severe Crohn's disease （CD） with the syndrome of cold and heat in complexity and the effect of the therapy on intestinal flora. MethodEighty patients were randomized based on the random number table method into a control group （40 cases） and an observation group （40 cases）. The control group was treated with VDZ， and the observation group was treated with modified Banxia Xiexintang （1 bag per day） combined with VDZ. The treatment in both groups lasted for 14 weeks and the follow-up lasted until the 52th weeks. The CD activity index （CDAI）， CD simplified endoscopic score （SES-CD）， inflammatory bowel disease questionnaire （IBDQ） score， and syndrome score of cold and heat in complexity were assessed before treatment， after treatment， and at the end of follow-up. The levels of hemoglobin （HGB）， hematocrit （HCT）， albumin （ALB）， C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-17 （IL-17）， and fecal calprotectin （FC） were measured before and after treatment. Intestinal flora was examined before and after treatment. The safety of the therapy was evaluated. ResultCompared with those before treatment， the scores of CDAI， SES-CD， and the syndrome of cold and heat in complexity decreased （P<0.05） and the IBDQ score increased after treatment （P<0.05）. Compared with those before treatment， the scores of CDAI， SES-CD， and the syndrome of cold and heat in complexity increased （P<0.05） and the IBDQ score decreased （P<0.05） at the end of follow-up. After treatment and at the end of follow-up， the observation group had lower scores of CDAI， SES-CD， and syndrome of cold and heat （P<0.05） and higher IBDQ score （P<0.05） than the control group. Moreover， the observation group had higher clinical remission rate（χ2=4.381，3.962） and response rate（χ2=5.541，4.306） and lower non-response rate（χ2=6.646，4.306） than the control group at the two time points （P<0.05）. The endoscopic remission rate（χ2=4.072，3.985） and response rate（χ2=4.528，5.161） in the observation group were higher than those in the control group （P<0.05）. After treatment， the HGB， HCT， and ALB levels in both groups elevated， and the observation group had higher levels than the control group （P<0.05）. The treatment in both groups lowered the levels of CRP， IL-6， TNF-α， IL-17， and FC （P<0.05）， and the observation group had lower levels of CRP， IL-6， TNF-α， IL-17， and FC than the control group after treatment （P<0.05）. The relative abundance of Bifidobacterium， Lactobacillus， and Prevotella increased （P<0.05）， while that of Proteus， Klebsiella， and Enterococcus decreased （P<0.05） in the two groups after treatment. Moreover， the changes in the relative abundance of these bacteria in the observation group were more obvious than those in the control group （P<0.05）. No adverse reactions related to the modified Modified Banxia Xiexintang were observed during the study period. ConclusionModified Banxia Xiexintang combined with VDZ can play a synergistic role and has good short-term and long-term efficacy. This therapy can improve the nutritional status， regulate intestinal flora， and reduce inflammatory injury in the treatment of moderate to severe active CD patients with the syndrome of cold and heat in complexity without causing severe adverse reactions.

Banxia Xiexintang Regulates Autophagy of Interstitial Cells of Cajal in Gastric Antrum of Rats with Gastric Electric Dysrhythmia / 中国实验方剂学杂志

ObjectiveTo observe the effect of Banxia Xiexintang on the autophagy of interstitial cells of Cajal （ICCs） in the gastric antrum of rats with gastric electric dysrhythmia， and explore the protective effect and regulatory mechanism. MethodThirty-two SD rats were randomly assigned into a normal group， a model group， a Banxia Xiexintang （24.68 g·kg-1） group， and a positive drug （2.7 mg·kg-1） group. The rat model of gastric electric dysrhythmia was established by the method of dieting every other day and drinking dilute hydrochloric acid， and Banxia Xiexintang and the positive drug were administrated for intervention. The body weight of each rat was recorded weekly. The gastric electric activity was recorded by the biological function experimental system. The ultrastructural changes of the gastric antrum tissue were observed by a transmission electron microscope. The co-expression of receptor tyrosine kinase （c-kit）/mammalian homolog of yeast Atg6 （Beclin1） in the gastric antrum tissue was detected by double immunofluorescence labeling method. The expression of microtubule-associated protein 1 light chain 3B （LC3B） and p62 protein in the gastric antrum tissue was determined by Western blot， and the LC3BⅡ/Ⅰ ratio was calculated. ResultCompared with the normal group， the modeling reduced the body weight （P<0.01） and decreased the dominant frequency and dominant power of gastric electricity （P<0.01）. In addition， the modeling caused ultrastructural damage of ICCs in gastric antrum， degeneration and necrosis of organelles， and appearance of a small number of autophagic vesicles. The results of double immunofluorescence labeling showed that the modeling inhibited the positive expression of c-kit and promoted the positive expression of Beclin1 in gastric antrum tissue. Western blot results showed that the modeling increased the ratio of LC3BⅡ/Ⅰ （P<0.01） and down-regulated the expression of p62 protein （P<0.01） in the gastric antrum tissue. Compared with the model group， Banxia Xiexintang and the positive drug increased the body weight （P<0.01） and the dominant frequency and dominant power of gastric electricity （P<0.01）， repaired the ultrastructural damage of ICCs in gastric antrum tissue， promoted the positive expression of c-kit and inhibited the positive expression of Beclin1 in the gastric antrum tissue. Furthermore， Banxia Xiexintang up-regulated the expression of p62 （P<0.05） and inhibited the transformation of LC3BⅠ into LC3BⅡ in gastric antrum tissue （P<0.05）. ConclusionBy regulating the expression of autophagy-related proteins， Banxia Xiexintang can reduce the autophagy and regulate the number and structure of ICCs and thus improve the gastric electric rhythm of rats， which preliminarily explains the mechanism of Banxia Xiexintang in the treatment of epigastric stuffiness.

Mechanism of Banxia Xiexintang in Prevention and Treatment of Gastric Cancer： A Review / 中国实验方剂学杂志

Gastric cancer （GC） is one of the common malignant tumors， and the incidence and mortality of GC in China rank first in the world. At present， the pathogenesis of GC has not been fully clarified. Although surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy have achieved good results in the treatment of GC， there are still many complications， decreased sensitivity， and severe side effects. Banxia Xiexintang， derived from Treatise on Cold Damage and Miscellaneous Diseases（《伤寒杂病论》）， has been clinically used for more than 2000 years with the effects of combining cold and warm drugs， dissipating mass， and relieving stuffiness， and is a classic prescription for treating digestive tract diseases in later generations. Through clinical observation and experimental research， it is found that Banxia Xiexintang and its single drugs have good effect in preventing and treating GC. Chinese medicine has multi-component and multi-target characteristics and can treat GC through various mechanisms. Therefore， it is necessary to carry out systematic and in-depth research from the aspects of molecular biology and network pharmacology， and comprehensively reveal the mechanism of Banxia Xiexintang in preventing and treating GC. At present， the mechanism of Banxia Xiexintang in treating GC mainly focuses on inducing apoptosis of GC cells， inhibiting proliferation， migration， and invasion of GC cells， protecting peritoneal mesothelial cells， inhibiting peritoneal metastasis of GC cells， regulating GC microenvironment， and inhibiting the malignant transformation of bone marrow mesenchymal stem cells （BMSCs）. This research group is committed to the prevention and treatment of GC with Banxia Xiexintang， aiming to comprehensively reveal the mechanism of action and the pharmacodynamic material basis of Banxia Xiexintang in the prevention and treatment of GC， and provide an important scientific basis for further clinical application of Banxia Xiexintang. After searching CNKI， PubMed， Wanfang Data， VIP， and other databases， this paper summarized Banxia Xiexintang in the treatment of GC from the aspects of prescription basis， material basis， network pharmacology， clinical and experimental studies， etc.， so as to provide references for further research on pharmacological effect of Banxia Xiexintang and its application in the clinical treatment of GC.

Effect of Banxia Xiexintang-containing Intestinal Absorption Solution on PMN-MDSCs Apoptosis in Gastric Cancer Microenvironment / 中国实验方剂学杂志

ObjectiveTo observe the effect of Banxia Xiexintang （BXT）-containing intestinal absorption solution on the apoptosis of polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） in gastric cancer microenvironment. MethodBXT-containing intestinal absorption solution was prepared， and gastric cancer cells and PMN-MDSCs were non-contact co-cultured in Transwell chamber to establish gastric cancer microenvironment. Cell counting kit-8 （CCK-8） assay was used to screen the optimal intervention concentration and time of 0-100% BXT-containing intestinal absorption solution prepared by 0.63 g·mL-1 reconstitution solution. Cells were classified into blank group， model group， oxaliplatin group （10 mg·L-1）， and BXT （26%， 18%， 10% BXT-containing intestinal absorption solution） group， and the apoptosis of PMN-MDSCs was detected by flow cytometry. The expression of apoptosis-related B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteine-aspartic acid protease-3 （Caspase-3） in PMN-MDSCs was detected by Western blot. ResultAfter treatment for 24 h and 48 h， the PMN-MDSCs-inhibiting rate was increased by 5%， 50%， 75%， and 100% BXT-containing intestinal absorption solution compared with that in the blank group （P<0.05， P<0.01）. At 72 h， the PMN-MDSCs-inhibiting rate by 50% BXT-containing intestinal absorption solution was lower than that at 48 h （P<0.01）， and the PMN-MDSCs-inhibiting rate by 5%， 75%， and 100% BXT-containing intestinal absorption solution showed no significant difference from that at 48 h. Moreover， the half-maximal inhibitory concentration （IC50） at 48 h was 18.40%. Thus， 18% BXT-containing intestinal absorption solution and 48 h were the optimal intervention concentration and time. The survival rate of PMN-MDSCs in model group was higher than that in the blank group （P<0.05）， and the apoptosis rate was lower than that in the blank group （P<0.05）. Compared with model group， BXT containing intestinal absorption solution lowered the survival rate and raised apoptosis rate of PMN-MDSCs （P<0.05）， particularly the 26% BXT-containing intestinal absorption solution （P<0.05）. The expression of Bax and Caspase-3 in PMN-MDSCs was lower in the model group than in the blank group （P<0.05）， and the expression of Bcl-2 was higher in the model group than in the blank group （P<0.05）. The expression of Caspase-3 in PMN-MDSCs increased （P<0.05） and the expression of Bcl-2 decreased （P<0.05） in oxaliplatin group and BXT group compared with those in the model group. The expression of Bax rose in oxaliplatin group and BXT group （10% BXT-containing intestinal absorption solution） （P<0.05）. ConclusionBXT can induce the apoptosis of PMN-MDSCs by regulating the expression of apoptosis-related proteins Bax， Caspase-3， and Bcl-2 in gastric cancer microenvironment.

Effect of Banxia Xiexintang-containing Intestinal Absorption Solution on Migration and Invasion of PMN-MDSCs in Gastric Cancer Microenvironment / 中国实验方剂学杂志

ObjectiveTo observe the effect of Banxia Xiexintang containing intestinal absorption solution （BXCIAS） on migration and invasion of polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） in gastric cancer microenvironment. MethodThe complex solution （containing 0.63 g·mL-1 crude drug） was prepared. Gastric cancer cells were subjected to non-contact co-culture with PMN-MDSCs in Transwell chamber to create gastric cancer microenvironment. Cell counting kit-8 （CCK-8） assay was used to screen the optimal intervention concentration and time of BXCIAS on PMN-MDSCs for subsequent experiment. The blank group， model group， FAK inhibitor group， and BXCIAS groups （26%， 18%， and 10%） were designed. Scratch assay and Transwell assay were employed to detect the migration and invasion ability of PMN-MDSCs， and enzyme-linked immunosorbent assay （ELISA） to measure the expression of vascular endothelial cell growth factor （VEGF） and matrix metalloproteinase-9 （MMP-9） in tumor microenvironment. The expression levels of PMN-MDSCs pathway-related proteins FAK， phosphorylated （p）-FAK， protein tyrosine kinase （Src）， and p-Src were detected by Western blot. ResultThe inhibition rates of PMN-MDSCs by 5%， 50%， 75%， and 100% BXCIAS at 48 h were higher than those at 24 h （P<0.05， P<0.01）. The inhibition rate of PMN-MDSCs by 50% BXCIAS at 72 h was lower than that at 48 h （P<0.01）， and the inhibition rates by 5% and 100% BXCIAS at 72 h were higher than those at 48 h （P<0.05， P<0.01）. There was no significant difference in the inhibition rate by other concentration levels at 48 h. The half-maximal inhibitory concentration （IC50） at 48 h was 18.09%， indicating that 18% BXCIAS and 48 h were the optimal concentration and time， respectively. The migration distance of PMN-MDSCs was large （P<0.01）， and the number of migrating and invading cells increased （P<0.01） in the mode group compared with those in the blank group. Compared with model group， FAK inhibitor and BXCIAS at different concentration decreased the migration distance of PMN-MDSCs （P<0.01）， and the number of migrating and invading cells （P<0.01）， especially the 26% BXCIAS （P<0.01）. The expression of PMN-MDSCs pathway-related proteins FAK， p-FAK， Src and p-Src （P<0.01） and the expression of VEGF and MMP-9 （P<0.01） were higher in the model group than in the blank group. Compared with model group， FAK inhibitor and BXCIAS （26%， 18%， 10%） decreased the expression of FAK， p-FAK， and Src （P<0.01）， and FAK inhibitor and 18% BXCIAS reduced the expression of p-Src （P<0.01）， and the expression of VEGF and MMP-9 （P<0.01）. ConclusionBXCIAS can inhibit the migration and invasion of PMN-MDSCs by down-regulating the expression of FAK， p-FAK， Src， and p-Src proteins in the FAK signaling pathway of PMN-MDSCs in gastric cancer microenvironment.

Effect of Banxia Xiexintang on NLRP3/Caspase-1 Pyroptosis Pathway in Rats with Ulcerative Colitis / 中国实验方剂学杂志

ObjectiveTo explore the effect of Banxia Xiexintang （BXT） on the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase-1） pyroptosis pathway and its downstream factors in rats with ulcerative colitis （UC）， and to explain the mechanism of BXT in the treatment of UC. MethodSD rats were randomly divided into normal control group， model group， low- and high-dose BXT groups （6.3， 12.6 g·kg-1·d-1）， and salazosulfapyridine （SASP） group （0.42 g·kg-1·d-1）， with 7 rats in each group. The UC model was induced by intragastric administration of 2.5% dextran sodium sulfate （DSS） solution for 10 days， followed by drug intervention for 7 days. The general state of rats was observed during the experiment， and the disease activity index （DAI） score was calculated during the administration period. At the end of the experiment， colonic tissues were collected for hematoxylin-eosin （HE） staining to observe the pathological changes and the curative effect of BXT. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA transcriptional levels of NLRP3， Caspase-1， gasdermin D （GSDMD）， and interleukin （IL）-1β in colonic tissues. Western blot was used to detect the protein expression of NLRP3， Caspase-1， GSDMD， and IL-1β in colonic tissues to explore the therapeutic mechanism of BXT. ResultCompared with the normal control group， the model group showed increased DAI score， pathological changes in colonic tissues， and up-regulated mRNA and protein expression of NLRP3， Caspase-1， GSDMD， and IL-1β （P<0.05， P<0.01）. Compared with the model group， the groups with drug intervention showed reduced DAI scores and improved pathological changes in colonic tissues. The mRNA and protein expression levels of NLRP3， Caspase-1， GSDMD， and IL-1β in colonic tissues of the BXT groups were significantly down-regulated or tended to be down-regulated， especially in the low-dose BXT group （P<0.05， P<0.01）. ConclusionBXT can inhibit pyroptosis and alleviate inflammation in rats with UC by regulating the NLRP3/Caspase-1 pathway.

Banxia Xiexintang and Its Disassembled Prescriptions Regulate Colonic Mucosal Immunity in Young Rats with Flora Disorder / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and possible mechanism of Banxia Xiexintang and its disassembled prescriptions in regulating the flora disorder induced by mixed antibiotics in young rats. MethodSeventy male BALB/C young rats were randomly assigned into 7 groups： blank group， model group， Bifidobacterium tetralogy viable tablets （0.68 g·kg-1） group， Banxia Xiexintang （9.1 g·kg-1） group， Xinkai （3.19 g·kg-1） group， Kujiang （1.82 g·kg-1） group， and Ganbu （4.1 g·kg-1） group， with 10 rats in each group. Except the blank group， the other groups were given mixed antibiotics by gavage to induce intestinal flora disorder. After 14 days， the rats in different drug groups were administrated with corresponding drugs by gavage， and those in the blank group and model group with the same amount of normal saline once a day for 14 days. After that， fecal samples were collected aseptically for 16S rDNA sequencing of intestinal flora， and lipopolysaccharide （LPS， 10 mg·kg-1） was injected intraperitoneally to induce inflammatory reaction. The tissue morphology of colonic mucosa was observed via hematoxylin-eosin （HE） staining， and the macrophage infiltration of colonic mucosa was observed via toluidine blue staining and immunohistochemistry. The expression of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10） mRNA were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the modeling changed the intestinal flora structure of the young rats （P<0.01）， damaged the colonic mucosa， reduced the macrophage infiltration， and down-regulated the mRNA levels of IL-1β， IL-6， IL-8， TNF-α， and IL-10 （P<0.01）. Compared with the model group， bifidobacterium quadruple viable tablets， Banxia Xiexintang and its disassembled prescriptions increased the diversity of intestinal flora and the relative abundance of beneficial bacteria such as Bacteroidetes and Firmicutes （P<0.01）. At the same time， they ameliorated colonic mucosal injury （P<0.05， P<0.01）， increased macrophage infiltration （P<0.05， P<0.01）， and up-regulated the mRNA levels of IL-6， IL-8， and TNF-α （P<0.01）. The mRNA level of IL-1β was up-regulated in Bifidobacterium tetralogy viable tablets， Banxia Xiexintang， Kujiang， and Ganbu groups （P<0.01）， and that of IL-10 was up-regulated in Bifidobacterium tetralogy viable tablets， Banxia Xiexintang， Xinkai， and Ganbu groups （P<0.01）. ConclusionBanxia Xiexintang and the disassembled prescriptions can adjust the intestinal flora of young rats exposed to antibiotics and protect the immune barrier of colonic mucosa after intestinal flora disorder. In particularly， the whole prescription of Banxia Xiexintang demonstrates the best performance.

Mechanism of Banxia Xiexintang on Rats with Chronic Gastritis Based on Quantitative Proteomics / 中国实验方剂学杂志

Objective:To study the biological basis of Banxia Xiexintang against chronic gastritis by using quantitative proteomics. Method:The experimental rats were divided into normal group，chronic gastritis model group，and Banxia Xiexintang group. The chronic gastritis model was established four weeks later by gavage with 56% ethanol. After treatment，the stomach tissues were stained with hematoxylin and eosin （HE） to observe the histopathological damage and improvement of gastric tissue in each group. The protein in gastric tissue was extracted. The differential proteins among different groups were studied by quantitative proteomics using tandem mass spectrometry tag（TMT），and the key differentially expressed proteins（DEPs） were verified by Western blot. Result:A total of 4 452 proteins were identified from rat stomach tissues，of which 318 proteins were different between the model and the normal group. After the intervention of Banxia Xiexintang，compared with the model group，there were a total of 258 differential proteins， which were mainly enriched in cell killing，nucleoid and hijacked molecular function. Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment included tricarboxylic acid（TCA） cycle，steroid hormone biosyntheis，and Retrograde endocannabinoid signaling，as well as phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt），nuclear transcription factor-<italic>κ</italic>B（NF-<italic>κ</italic>B） signal pathways. Western blot verification found that 14-3-3 theta，Tenascin-C，ntercellular adhesion molecule-1（ICAM-1），stem cell factor（SCF），Caspase-3，GTPase of the Immunity-associated protein 4（GIMAP4） and mitochondrial pyruvate carrier 1（Mpc1） might be the crucial proteins for the treatment of chronic gastritis. Conclusion:The mechanism of Banxia Xiexintang in the treatment of chronic gastritis involves energy metabolism，hormone regulation，inflammation and immune processes. The target proteins found by differential proteomics and the signaling pathways may be the biological basis of Banxia Xiexintang in the treatment of chronic gastritis.

Regulatory Effect of Modified Banxia Xiexintang on Insulin Resistance of Patients with Nonalcoholic Fatty Liver / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Banxia Xiexintang on nonalcoholic fatty liver （NAFLD） and the regulatory effect on insulin resistance （IR）. Method:One hundred and forty patients were randomly divided into control group and observation group. A total of 63 patients in control group completed the therapy （4 patients fell off or were lost to follow-up， 3 were eliminated）， while 65 patients in observation group completed the therapy （5 patients fell off or were lost to follow-up， none was eliminated）. Both groups' patients got lifestyle intervention， liver protection and lipid regulation. Patients in control group got Huazhi Rougan granule， 1 pack/time， 3 times/day. Patients in observation group got modified Banxia Xiexintang， 1 dose/day. And the course of treatment for the two groups was 12 weeks， and a 12 week follow-up was recorded. Before and after treatment and during the follow-up， fat content of liver was recorded by instantaneous elastic recorder， fasting blood glucose （FBG） and fasting insulin （FINS） were detected， and insulin sensitivity index （ISI）， insulin resistance index （HOMA-IR） and islet <italic>β</italic> cell function index （HOMA-<italic>β</italic>） were detected. After treatment， B-mode ultrasonography and ratio of liver/spleen CT were detected. And levels of alanine transaminase （ALT）， aspartate transaminase （AST）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， adiponectin， leptin， serine protease inhibitor （Vaspin）， tumor necrosis factor （TNF）-<italic>α</italic> and interleukin-6 （IL-6） were detected. And the safety was evaluated. Result:CAP and HOMA-IR in observation group were lower than those in control group after treatment and during the follow-up （<italic>P</italic><0.01）， and ISI and HOMA-<italic>β</italic> were higher than those in control group （<italic>P</italic><0.01）. Amelioration of indexes of blood lipid was better than those in control group （<italic>P</italic><0.01）. Levels of ALT， AST， FBG and FINS were lower than those in control group （<italic>P</italic><0.01）. Scores of traditional Chinese medicine （TCM） syndromes were lower than those in control group （<italic>P</italic><0.01）， ratio of liver/spleen CT and adiponectin was higher than that in control group （<italic>P</italic><0.01）. Levels of TNF-<italic>α</italic>， IL-6， vaspin and leptin were lower than those in control group （<italic>P</italic><0.01）. B-ultrasound efficacy and fat content of liver were superior to those of control group （<italic>P</italic><0.05）. There were no serious adverse events and drug-related adverse reactions. Conclusion:Modified Banxia Xiexintang can regulate glucose and lipid metabolism， improve insulin sensitivity and HOMA-<italic>β</italic> cell function， improve IR， regulate adipocytokines and inflammatory factors， relieve clinical symptoms and liver fat content， and improve CT ratio of liver/spleen， with a better clinical efficacy and safety.

Effect and Mechanism of Banxia Xiexintang on Rats with Chronic Atrophic Gastritis Based on Keap1/Nrf2/ARE Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the mechanism of Banxia Xiexintang （BXXX） in preventing and treating chronic atrophic gastritis （CAG） through Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway. Method:SD rats were divided into a normal group （<italic>n</italic>=12） and an experimental group for CAG model induction. The model rats were then randomly divided into a model group， a vatacoenayme （VG） group （60 mg·kg^-1）， and high- （280 mg·kg^-1）， medium- （140 mg·kg^-1）， and low-dose （70 mg·kg^-1） BXXX groups. The doses in the BXXX groups were equivalent to 28， 14， and 7 g·kg^-1 crude drugs. The rats in the normal group and the model group received distilled water at an equal volume， and those in the VG group and the BXXX groups were treated correspondingly by gavage. After 12 weeks of treatment， hematoxylin-eosin （HE） staining was carried out to observe pathological changes in the gastric mucosa of CAG rats. Western blot and real-time fluorescence-based quantitative PCR was used to detect the protein and mRNA expression levels of Nrf2， glutathione S-transferase （GST）， and NAD （P）H：quinone oxidoreductase 1 （NQO1） in the gastric mucosa of CAG rats. Result:Compared with the normal group， the model group showed increased protein and mRNA expression levels of Nrf2， NQO1， and GST in the gastric mucosa of the rats （<italic>P</italic><0.05）， atrophic gastric mucosa， and even intestinal metaplasia. The protein and mRNA expression levels of Nrf2， NQO1， and GST in the VG group and the high- and medium-dose BXXX groups were lower than those in the model group （<italic>P</italic><0.05）， and gastric mucosa atrophy and intestinal metaplasia were significantly improved， especially in the high-dose BXXX group. However， the effect in the low-dose BXXX group was not significant. Conclusion:BXXX can blunt the transcriptional activity of Nrf2， shut down Nrf2 signaling pathway， and reduce the expression levels of NQO1 and GST to achieve normal oxidation-anti-oxidation balance， which may be one of its action mechanisms in the treatment of CAG.

Effect of Banxia Xiexintang-containing Serum on Epithelial-mesenchymal Transition of Peritoneal Mesothelial Cells Induced by Gastric Cancer-derived Exosomes / 中国实验方剂学杂志

Objective:To investigate the effect of Banxia Xiexintang on the epithelial-mesenchymal transition （EMT） of human peritoneal mesothelial cell line （HMrSV5） induced by gastric cancer-derived exosomes （Exo）. Method:Banxia Xiexintang-containing serum was prepared and the human gastric cancer NCI-N87-derived exosomes （NCI-N87-Exo） were extracted， followed by their identification by transmission electron microscopy and Western blotting and labeling with 1，1-dioctadecyl-3，3，3，3- tetramethylindocarbocyanine perchlorate （Dil）. The cells were divided into the blank group， model group， and low-， medium-， and high-dose （13.5，27，54 g·kg^-1） Banxia Xiexintang groups. HMrSV5 cells in the blank group were cultured alone， the ones in the model group with 100 mg·L^-1 NCI-N87-Exo， and those in the low-， medium-， and high-dose Banxia Xiexintang groups with 100 mg·L^-1 NCI-N87-Exo plus low-， medium-， and high-dose 10% Banxia Xiexintang-containing serum， respectively. Confocal laser microscope was used to observe the uptake of NCI-N87-Exo by HMrSV5 cells at 24 h， 48 h and 72 h. Seventy-two hours later， the morphological changes in HMrSV5 cells were observed. The protein expression levels of E-cadherin， cytokeratin 19 （CK19）， <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA）， elastin， and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， Smad2/3， and p-Smad2/3 were assayed by Western blot. Result:It was observed under the transmission electron microscope that NCI-N87-Exo showed an oval or dish-shaped vesicle structure with a particle size ranging from 40 to 80 nm. Exo marker proteins CD9 and CD63 were highly expressed while calreticulin was not expressed， implying that the NCI-N87-Exo was confirmed. After 24 h， 48 h， 72 h of co-culture， it was observed under the fluorescence microscope that NCI-N87-Exo were taken up by HMrSV5 cells， which was positively correlated with time. Compared with the blank group， Banxia Xiexintang significantly inhibited the uptake of NCI-N87-Exo by HMrSV5 cells， with better effect noticed in the middle- and high-dose Banxia Xiexintang groups（<italic>P</italic><0.05，<italic>P</italic><0.01）. After intervention with Banxia Xiexintang-containing serum， the HMrSV5 cells were arranged densely， and the intercellular space was significantly reduced， with the most obvious changes present in the high-dose Banxia Xiexintang group. Western blot revealed that the protein expression levels of E-cadherin and CK19 in HMrSV5 cells after being intervened with the medium- and high-dose Banxia Xiexintang-containing serum were increased significantly as compared with those in the blank group， whereas the levels of <italic>α</italic>-SMA and Elastin were decreased significantly （<italic>P</italic><0.01）. Banxia Xiexintang-containing serum at the low， medium， and high doses remarkably down-regulated TGF-<italic>β</italic>₁ and p-Smad2/3 protein expression（<italic>P</italic><0.05，<italic>P</italic><0.01）. However， there was no significant change in Smad2/3. Conclusion:NCI-N87-Exo can be taken up by HMrSV5 cells to induce EMT. Banxia Xiexintang can inhibit the uptake of NCI-N87-Exo by HMrSV5 cells and the resulting EMT induced by NCI-N87-Exo， which is related to the regulation of TGF-<italic>β</italic>₁/Smads signaling pathway.

Application of DESI-MSI in Quality Control of Banxia Xiexintang / 中国实验方剂学杂志

Objective::To prepare 15 batches of Banxia Xiexintang substance benchmark and lyophilized powder from different places, and the lyophilized powder was analyzed by ultra-high performance liquid chromatography with diode array detection (UHPLC-DAD) and desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) in order to investigate the advantages of DESI-MSI in quality control of famous classical formulas. Method::Taking Banxia Xiexintang as the research model, fingerprints of the substance benchmark and lyophilized powder were established by UHPLC-DAD, and the content of index components and the yield of dry extract were also investigated. Meanwhile, as the research carrier, the lyophilized powder corresponding to Banxia Xiexintang was dissolved in methanol and dotted on qualitative filter paper with 5 μL quantitative capillary, and fixed it on the slide to make samples. The samples were analyzed on a DESI-MSI system in positive and negative ion mode with methanol-formic acid (1 000∶1, flow rate of 3 μL·min-1) as spray solvent, N2 as spray gas (pressure of 0.5 MPa). The scanning range was 100-1 200 Da, the spatial resolution was 300 μm, the spray voltage was 3 kV, the sampling cone voltage was ±40 V, incidence angle of sprayer was 60 degree, its collection angle was 10 degree, the ion source temperature was 120 ℃. Result::DESI-MSI could not only detect the index components of liquiritin, baicalin and wogonoside, as well as the common peaks of liquiritin apioside, berberine and glycyrrhizic acid, but also analyzed them semi-quantitatively, the analysis results were basically consistent with UHPLC-DAD. At the same time, DESI-MSI could detect 16 other components from Glycyrrhizae Radix et Rhizoma, Coptidis Rhizoma, Scutellariae Radix, Jujubae Fructus and Ginseng Radix et Rhizoma, such as licoricesaponin G2, palmatine, coptisine, rutin and ginsenoside Rg1, and present their relative content visually. The qualitative analysis ability of DESI-MSI was much better than UHPLC-DAD. Conclusion::DESI-MSI can be used as the quality control method for substance benchmark and lyophilized powder and dispensing granules of famous classical formulas with advantages of high sensitivity, strong analytical ability, no complex sample processing, qualitative and relative content analysis of complex samples without reference substance.

Effect and Mechanism of Modified Banxia Xiexintang on Depression During Perimenopause / 中国实验方剂学杂志

Objective::To observe the effect of modified Banxia Xiexintang on depression during perimenopause, in order to study itseffecton 5-hydroxytryptamine (5-HT) and proinflammatory factors. Method::One hundred and thirty-nine patients were randomly divided into control group (69 cases) and observation group (70 cases) by random number table.Patients in control group got tibolone tablets, 2.5 mg/time, 1 time/day, and paroxetine hydrochloride tablets, 20 mg/time, 1 time/day.In addition to the therapy in control group, patients in observation group were added with modified Banxia Xiexintang, 1 dose/day.The course of treatment was 8 weeks.And before and after treatment, Hamilton depression scale for-17 items (HAMD-17), Zung's self-rating depression scale (SDS), hamilton anxiety scale (HAMA), improvement Kupperman(KI), liver depression and spleen deficiency syndrome, menopause-specific quality of life questionnaire (MENQOL) and treatment emergent symptom scale (TESS) were scored, and levels of 5-HT, rain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected. Result::After treatment, scores of HAMD-17 and SDS in observation group were lower than those in control group (P<0.01). And the effect on trea depression in observation group was better than that in control group (Z=2.074, P<0.05). The degree of depression in observation group was ligher than that in control group (Z=2.157, P<0.05). And scores of HAMA, KI and liver depression and spleen deficiency syndrome were lower than those in control group (P<0.01). The severity of perimenopausal syndrome was ligher than that in control group (Z=2.046, P<0.05). And scores of vasomotor symptoms and psychological symptoms of MENQOL scale and the total scores were lower than those in control group (P<0.05). Levels of 5-HT and BDNF were higher than those in control group (P<0.01), while levels of IL-1β, TNF-α and TESS were lower than those in control group (P<0.01). Conclusion::In addition to theroutine western medicine, modified Banxia Xiexintang can alleviate the severity of depression, release the symptoms of depression, anxiety and perimenopausal syudrome(PMS), improve the quality of life, inhibit pro-inflammatory factors, and enhance the expressions of 5-HT and BDNF, with no adverse event.

Analysis of Banxia Xiexintang Based on Ancient Literatures / 中国实验方剂学杂志

Banxia Xiexin Tang is one of the classic prescriptions for treating digestive system diseases.In this paper，using the method of bibliometrics，information of Banxia Xiexintang in ancient Chinese medical literatures were collected and screened out 399 effective data from 238 kinds of ancient books．Based on the statistics and analysis of the history，drug composition，main disease and syndrome，principle of prescription，dosage，processing，preparation，decocting and taking methods of Banxia Xiexin Tang，it is found that Banxia Xiexin Tang originated from Treatise on Febrile and Miscellaneous Disease written by ZHANG Zhong-jing，a famous physician in the Eastern Han dynasty，it is composed of seven herbs，namely，Pinelliae Rhizoma，Scutellariae Radix，Zingiberis Rhizoma，Ginseng Radix et Rhizoma，Glycyrrhizae Radix et Rhizoma Praeparata cum Melle，Coptidis Rhizoma，and Jujubae Fructus. It was mainly used to treat pizheng of mixed cold and heat. Most of the Banxia Xiexin Tang recorded in later generations follow the prescription composition and indications in Treatise on Febrile and Miscellaneous Disease and its clinical application has been extended and expanded，among the 352 literatures with the main diseases and syndromes recorded，the most common （341） were pizheng，accounting for about 96.88%，in addition，it is also used sporadically for shuzheng，malaria，nausea，damp-wen，jaundice，etc. Among the 122 documents with drug dosage records，nearly half of them are identical with the original records in Treatise on Febrile and Miscellaneous Disease. Among the 112 literatures with pharmaceutical processing，licorice （86） was the most，most of them were roasted （80），followed by pinellia ternata （79），and most of them were "decoction washing and sliding" （67）. Among the 111 documents recorded in the decoction method，most of them inherited Treatise on Febrile and Miscellaneous Disease by "removing the dross and again cooking" （68），there are also "Water Decoction" （32） and "Ginseng Radix et Rhizoma and Jujubae Fructus Decoction" （11）. Among the 108 documents with the method of taking medicine，nearly half of them inherited Treatise on Febrile and Miscellaneous Disease，which is "a liter of warm taking ，three times daily". Based on the ancient Chinese medical literatures，Banxia Xiexintang was systematically analyzed in order to provide more accurate ancient literature reference for the clinical application and development of classic prescriptions.