Abstract：ObjectiveTo explore the molecular mechanism of modified Guizhi Fulingwan in rats with uterine fibroids.MethodSeventy-two female adult SD rats of SPF grade were randomly divided into a model group， a normal group， and a preventive administration group. The model group and preventive administration group were established by estrogen and progestin loading method. After successful modeling， the rats in the model group were randomly divided into a western medicine group （mifepristone）， the high-dose traditional Chinese medicine（TCM） group， and a low-dose TCM group. All the rats were dosing as required once a day for 28 consecutive days. Hematoxylin-eosin（HE）staining was used to observe the morphological changes of the uterus. The micRNA gene chip was used to detect the expression profile of uterine micRNA gene. Differential expressions of micRNA were screened by bioinformatics methods. Gene function enrichment was used to predict the possible signaling pathways in rats with uterine fibroids by modified Guizhi Fulingwan.ResultCompared with the normal group， microRNA of the model group was 1 up-regulated and 9 down-regulated. Compared with the model group， microRNA of the high-dose group of TCM group was 2 up-regulated and 1 down-regulated， in the preventive administration group， 9 was up-regulated and 2 was down-regulated. Gene function enrichment analysis indicated that four signaling pathways were closely related to uterine fibroids. They were mitogen-activated protein kinase （MAPK） signaling pathway， Wnt signaling pathway， mammalian rapamycin target protein （mTOR） signaling pathway and vascular endothelial cell growth factor （VEGF） signaling pathway.ConclusionModified Guizhi Fulingwan affected the expression profile of micRNA in rat model of uterine fibroids induced by estrogen and progesterone， suggesting that modified Guizhi Fulingwan may involve in a variety of biological processes such as signal transduction and gene regulation in the treatment of uterine fibroids.
Keywords：uterine fibroids;modified Guizhi Fulingwan;estrogen and progesterone induction model;gene chip
Abstract：ObjectiveTo observe the effect of modified Shuyuwan in amyloid precursor protein/ presenilin 1 （APP/PS1） dementia mice on cognitive and memory impairment and to explore its mechanism.MethodThe 40 APP/PS1 mice were divided into model group （given Physiological saline）， low and high-dose modified Shuyuwan （14，64 g·kg-1）group， and donepezil group （1 mg·kg-1） and 10 wild mice were set as the blank control group （given Physiological saline）. All of the mice were administered intragastrically for 35 days. The memory and space exploration ability of mice was detected by Morris water maze， the morphology of mouse hippocampal neurons were observed by Nissl staining. The deposition of β amyloid 1-42（Aβ1-42） in mouse hippocampus was detected by immunohistochemistry， and the expression of ionized calcium-binding adapter molecule 1（Iba1）， a marker of hippocampal microglia （MG） and Nitric oxide synthase（iNOS）， a marker of actived MG， were detected by immunofluorescence. The protein expression of NLR family pyrin domain containing 3（Nlrp3）， Apoptosis-associated speck-like protein containing a Caspase-recruitment domain （ASC）， cysteine protease-1（Caspase-1）and interleukin-1 beta （IL-1β） were detected by Western blot， and the expression of IL-1β， tumor necrosis factor-α（TNF-α）and interleukin-18 （IL-18） mRNA were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）.ResultCompared with the blank control group， the memory and space exploration ability of the model group were significantly reduced （P<0.05）， the number of hippocampal neurons decreased， the deposition of Aβ1-42 increased， the markers of actived MG Iba1，iNOS increased， the protein expression of Nlrp3， ASC， Caspase-1， IL-1β increased significantly （P<0.05）， and the mRNA expression of IL-1β， IL-18， and TNF-α increased significantly （P<0.05）. Compared with model group， the Chinese medicine group can improve the APP/PS1 mice's space exploration ability and memory ability （P<0.05）， increase the number of hippocampal neurons， reduce Aβ1-42 deposition， reduce the activation of MG， and reduce the protein expression of Nlrp3， ASC， Caspase-1 and IL-1β （P<0.05）， and reduced the expression of IL-1β mRNA （P<0.05）.ConclusionModified Shuyuwan can reduce the expression of IL-1β and other inflammatory factors in the hippocampus of APP/PS1 mice by inhibiting the Nlrp3/ASC/Caspase-1 pathway， and relieve nerve inflammation and pathological injury of AD.
Abstract：ObjectiveTo investigate the mechanism of Xiangsha Liujunzi Tang in improving liver lipid deposition in ApoE-/- atherosclerotic （AS） mice by affecting long noncoding RNA-HC （Lnc-HC）/microRNA-130b （miR-130b） in the regulation of cholesterol metabolism.MethodTotolly 10 C57BL/6J mice were selected as normal controls， and 30 healthy ApoE-/- mice fed with high fat diet for 12 weeks were then randomly divided into the model group， Xiangsha Liujunzi Tang group（19.12 g·kg-1·d-1） and simvastatin group（2.275 mg·kg-1·d-1）， with gavage administration for 4 weeks. The serum lipid level of mice was detected by automatic biochemistry analyzer， and the histopathological changes of liver cells were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect expression of long noncoding RNA-HC， and miR-130b. Real-time PCR and Western blot assay were used to detect gene and protein expression of peroxisome proliferator-activated receptor gamma （PPARγ）， liver X receptor （LXR）， ATP-binding cassette transporters A1 （ABCA1）， ATP-binding cassette transporters G1 （ABCG1）， ATP-binding cassette transporters G5 （ABCG5）， and ATP-binding cassette transporters G8 （ABCG8）.ResultCompared with the normal control group， the mice in the model group showed abnormal blood lipids， larger liver cells， obvious fat vacuoles， significantly increased expression of Lnc-HC， miR-130b in liver， and significantly decreased gene and protein expression of PPARγ， LXR， ABCA1， ABCG1， ABCG5， and ABCG8 in mice liver （P<0.05，P<0.01）. Compared with the model group， the abnormal blood lipid levels of the mice in the Xiangsha Liujunzi Tang group and the simvastatin group were improved， and the number of fatty vacuoles of liver cells was significantly reduced， the expression of liver Lnc-HC， miR-130b in Xiangsha Liujunzi Tang group decreased significantly （P<0.05，P<0.01）， the gene and protein levels of liver PPARγ， ABCA1， ABCG1， ABCG5， ABCG8 in mice of the Xiangsha Liujunzi Tang group and the simvastatin group showed an upward trend. Among them， the gene and protein expression of LXR protein in the liver of the Xiangsha Liujunzi Tang group was significantly up-regulated （P<0.05）.ConclusionXiangsha Liujunzi Tang may improve the lipid deposition in the liver of ApoE-/- AS mice by affecting Lnc-HC/miR-130b to regulate the cholesterol metabolism process mediated by PPARγ， thus playing a role in preventing and treating AS.
Abstract：ObjectiveTo investigate the effect of compatibility of Anemarrhenae Rhizoma-Phellodendri Chinensis Cortex couplet medicines on glucolipid metabolism in type 2 diabetic rats before and after salt-processing.MethodThe type 2 diabetic rat model was induced by high-fat and high-glucose diet combined with low dose streptozotocin （STZ）， the model rats were randomly divided into six groups， including the model group， metformin group （200 mg·kg-1）， and different compatibility groups of raw and salt-processed of Anemarrhenae Rhizoma and Phellodendri Chinensis Cortex （6.48 g·kg-1）. In addition， The same week old rats fed with normal diet were set as the blank group. After 30 d of continuous intragastric administration， changes of fasting blood glucose （FBG）， fasting serum insulin （FINS）， glycosylated serum protein （GSP）， hepatic glycogen， blood lipid ［total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， high density lipoprotein cholesterol （HDL-C）］， nonesterified fatty acid （NEFA）， adipocytokines ［adiponectin （ADP） and leptin）］， kidney function ［blood urea nitrogen （BUN） and creatinine （CRE）］ and other indicators of rats from different groups were detected， and the insulin sensitivity index （ISI） and insulin resistance index （HOMA-IR） were calculated， hematoxylin-eosin （HE） staining was used to observe the morphological changes of pancreas， liver and kidney of rats from different groups.ResultCompared with the model group， compatibility of Anemarrhenae Rhizoma-Phellodendri Chinensis Cortex couplet medicines before and after salt-processing all could decrease the levels of FBG， GSP， TC， TG， LDL-C， NEFA， leptin， BUN， CRE and HOMA-IR， and increase the contents of FINS， HDL-C， ADP， hepatic glycogen and ISI， among which the compatibility of salt-processed Anemarrhenae Rhizoma and salt-processed Phellodendri Chinensis Cortex had the most significant effect on regulating glucolipid metabolism in type 2 diabetic rats. The compatibility of all couplet medicines could improve the histopathological changes of pancreas， liver and kidney in type 2 diabetic rats， among which the compatibility of salt-processed Anemarrhenae Rhizoma and salt-processed Phellodendri Chinensis Cortex had the most prominent effect on repairing pathological damage.ConclusionThe compatibility of Anemarrhenae Rhizoma and Phellodendri Chinensis Cortex before and after salt-processing can improve glucolipid metabolism in type 2 diabetic rats， while the comprehensive effect of salt-processed Anemarrhenae Rhizoma and salt-processed Phellodendri Chinensis Cortex on lowering glucose and regulating lipid is the best.
Abstract：ObjectiveTo study the anti-inflammatory effects of low， middle， and high doses of Anchang decoction on ulcerative colitis in SD rats， and also explore the possible mechanism of Anchang decoction in the prevention and treatment of ulcerative colitis through the effect of different doses on miRNA-146a/non-receptor tyrosine protein kinase（JAK）/signal transduction and activator of transcription 3（STAT3）/cytokine signaling protein-3（SOCS-3） signal pathway and its downstream proteins.MethodThe experimental rats were divided into control group ， model group ， mesalazine group（1 g·kg-1） and Anchang decoction low（6 g·kg-1）， middle（12 g·kg-1）and high dose groups（24 g·kg-1）， with 10 rats in each group. Except for the control group， 2，4，6-trinitrobenzenesulfonic acid （TNBS）/ethanol enema was used in all the other groups to establish a rat model of ulcerative colitis for 14 days respectively. The general changes of the mental state， stool traits， hair and other general conditions of the rats were observed， and score was graded with reference to the disease activity index （DAI） table. The pathological changes of colon tissue of rats in each group were observed by hematoxylin-eosin （HE） staining. The levels of serum tumor necrosis factor-α（TNF-α）， interleukin-10（IL-10）， interleukin-17（IL-17）， interleukin-1β（IL-1β）and interleukin-6（IL-6）were detected by enzyme linked immunosorbent assay （ELISA）. The expression levels of JAK2， phosphorylation STAT3 （p-STAT3）， STAT3 and inhibitor of SOCS-3 in colon tissue were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of JAK2， p-STAT3， STAT3， SOCS-3 mRNA in rat colon and miRNA-146a in rat plasma.ResultCompared with the normal group， the expression of JAK2， p-STAT3， STAT3 protein and the expression of JAK2， p-STAT3 and STAT3 mRNA in the model group increased （P<0.05）， and the relative expression of miRNA-146a， SOCS-3 mRNA and SOCS-3 protein decreased in the model group （P<0.05）. Compared with the model group， the mental state， food intake， coat color， etc. of rats in the administration groups were significantly improved， the DAI score was significantly reduced （P<0.05）， the colonic ulcer tissues of rats in the administration groups were improved significantly， the expression levels of JAK2， p-STAT3， STAT3 protein and the expression of JAK2， p-STAT3 and STAT3 mRNA in the colon tissue of the administration groups were decreased （P<0.05）， and the relative expression levels of miRNA-146a， SOCS-3 mRNA and SOCS-3 protein were increased in the administration groups （P<0.05）.ConclusionAnchang decoction can alleviate ulcerative colitis and reduce the activation of inflammatory factors by affecting the expression of genes and proteins related to miRNA-146a/JAK/STAT/SOCS-3 signal transduction pathway.
Keywords：ulcerative colitis;Anchang decoction;non-receptor tyrosine protein kinase2（JAK2）;signal transduction and activator of transcription-3（STAT3）;miRNA-146a
Abstract：ObjectiveTo study the effect and related mechanism of Fuyou granule on danazol-induced precocious puberty model in rats.MethodTotally 21 cages of SD female rats were randomly divided into normal group， model group， Leuprorelin（0.1 g·kg-1） and Fuyou mixture group（37.9 g·kg-1）， and high-dose， mid-dose and low dose Fuyou granule groups（17.0，8.5，4.3 g·kg-1）. Rats at 5 days of age were given a single subcutaneous injection of 300 μg danazol to establish the precocious puberty model. After 10 days of modeling， drug intervention was started. Vaginal opening was examined at the age of 20 days， and the gonadal development was observed by hematoxylin-eosin （HE） staining. The levels of serum luteinizing hormone （LH）， follicle-stimulating hormone （FSH） and estradiol （E2） were determined by radioimmunoassay. The mRNA expressions of hypothalamic gonadotropin releasing hormone （GnRH）， Kiss-1， G protein-coupled receptor 54 （GPR54） were detected by Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and the expression of GnRH cells in the hypothalamus was detected by immunohistochemistry.ResultCompared with the normal group， the vaginal opening of the model group was significantly earlier， and the uterus and ovarian coefficients were significantly increased （P<0.05）， indicating that the danazol-induced precocious puberty model was successfully established. The expression levels of GnRH， Kiss-1， and GPR54 also increased significantly （P<0.05）， indicating that the danazol model can activate the HPG axis in advance， thereby inducing precocious puberty. Compared with the model group， the mid-dose Fuyou granule group significantly delayed the time of vaginal opening （P<0.01）， high-dose Fuyou granule group significantly reduced uterine wall thickness and uterine coefficient （P<0.05，P<0.01）， mid-dose group reduced ovarian coefficient and uterine wall thickness （P<0.05）. All the three dosage groups of Fuyou granule significantly reduced the content of serum hormones E2， LH and FSH （P<0.05，P<0.01）， reduced the expression levels of hypothalamic GnRH， Kiss-1 and GPR54 mRNA （P<0.05）， and decreased the expression of GnRH cells （P<0.05）.ConclusionFuyou granule can achieve therapeutic precocity by regulating the Kiss-1/GPR54 system and down-regulating the expression of GnRH to inhibit the activation of the HPG axis.
Abstract：ObjectiveTo observe the effect of Shuangyu Tiaozhi decoction on B-type scavenger receptor （SRB1）/cholesterol 7α-hydroxylase protein （CYP7A1）/farnesol X receptor （FXR） signaling pathway in liver of hypercholesterolemic rats， and its mechanism in reducing blood lipid.MethodAmong 40 SD rats， 8 were randomly selected as normal group， and the remaining 32 were successfully established as hypercholesterolemic model， and randomly divided into 4 groups： model group， low and high-dose Shuangyu Tiaozhi decoction groups （7.8， 15.6 g·kg-1）， and simvastatin group （4 mg·kg-1）， with 8 rats in each group. The drugs were continuously given for 8 weeks. Serum total cholesterol （TC）， triglyceride （TG） and liver TC，free cholesterol （FC） and total bile acid （TBA） were measured. The pathomorphological changes in liver were observed by Hematoxylin and eosin （HE） Staining. The mRNA and protein expressions of SRB1， CYP7A1 and FXR were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. The immunohistochemistry was used to detect CYP7A1 and FXR expressions in liver.ResultCompared with the normal group， TC， TG， FC levels in the model group were significantly increased， while the TBA level was markedly decreased， the morphology showed obvious liver steatosis， and significant declines in expressions of SRB1， CYP7A1， FXR were observed by Real-time PCR， Western blot and immunohistochemistry assays （P<0.05， P<0.01）. Compared with the model group， the levels of TC，TG，FC in each treatment group were reduced significantly， and the TBA level was increased markedly， the liver steatosis decreased significantly， the results of Real-time PCR， Western blot and immunohistochemistry assays showed significant increase in the expressions of SRB1， CYP7A1， FXR （P<0.05， P<0.01）. The therapeutic effect of high-dose Shuangyu Tiaozhi decoction group was more remarkable than that in low-dose Shuangyu Tiaozhi Decoction group （P<0.05）， with no obvious difference compared with simvastatin group.ConclusionShuangyu Tiaozhi decoction can promote hepatic RCT and synthesize bile acid by up-regulating SRB1/CYP7A1/FXR signaling pathway， so as to reduce the blood lipid levels and improve hepatic lipid metabolism of hypercholesterolemic rats.
Keywords：Shuangyu Tiaozhi decoction;hypercholesterolemia;lipid metabolism;reverse cholesterol transport;B-type scavenger receptor （SRB1）;cholesterol 7α-hydroxylase protein （CYP7A1）;farnesol X receptor （FXR）
Abstract：ObjectiveTo explore the intervention effect of Wenxin granule on endoplasmic reticulum stress apoptosis pathway and its related mechanism in rats with myocardial infarction.MethodLigating the left anterior descending coronary artery to establish the rat model， the rats were randomly divided into 5 groups， namely sham group， model group， betaloc group and low， high-dose Wenxin granule groups，10 in each group. The sham group and the model group were given 10 mL∙kg-1∙d-1 deionized water， the low， high-dose modified Wenxin groups were given 1.35， 2.7 g∙kg-1∙d-1 aqueous solution respectively， and the betaloc group was given 2.25 mg∙kg-1∙d-1 aqueous solution. After 14 days，the catheter method was used to detect the cardiac hemodynamics and hematoxylin-eosin staining （HE） was used to observe the pathological morphological changes. The levels of endoplasmic reticulum stress protein glucose regulatory protein 78（GRP78）， protein kinase R like endoplasmic reticulum kinase（PERK）， phosphorylated activated PERK（p-PERK）， activated transcription factor 6 （ATF6）， nuclear transcription factor X cassette binding protein（XBP1） and apoptosis protein C/EBP homologous protein（CHOP）， B cell lymphoma/leukemia-2（Bcl-2） and Bcl-2 associated X protein（Bax） were detected by Western blot. Deoxyribonucleotide end-transferase-mediated notch end labeling （TUNEL） was also used to detect the myocardial cell apoptosis.ResultCompared with control group， the levels of the maximum ascending rate of left ventricular pressure（+dp/dtmax）， the maximum descending rate of left ventricular pressure（-dp/dtmax） and the left ventricular systolic blood pressure（LVSP） were decreased significantly（P<0.05），but the level of the left ventricular end diastolic blood pressure （LVEDP） was significantly increased（P<0.05）. The expressions of GRP78， p-PERK， PERK， ATF6， XBP1， CHOP， Bax and apoptosis index were increased significantly （P<0.05，P<0.01）， while Bcl-2/Bax and Bcl-2 were decreased significantly（P<0.01） in model group. Compared with the model group， the levels of -dp/dtmax and Bcl-2 were increased significantly （P<0.05），while the level of the apoptosis index was decreased significantly（P<0.01） in low-dose Wenxin granule group. In high-dose Wenxin granule group， the levels of +dp/dtmax and -dp/dtmax were increased significantly（P<0.05，P<0.01）， the levels of endoplasmic reticulum stress pathway protein GRP78， p-PERK， PERK， ATF6， XBP1，apoptosis-related protein CHOP， Bax and apoptosis index were decreased significantly（P<0.01）， but Bcl-2 and Bcl-2/Bax were increased significantly （P<0.01）.ConclusionWenxin granule has effect in inhibiting excessive endoplasmic reticulum stress， reducing myocardial cell apoptosis and improving cardiac hemodynamics. Its molecular mechanism may be related to decrease the levels of GRP78， PERK， p-PERK， ATF6， XBP1， CHOP， Bax and increasing the expression of Bcl-2.
Abstract：ObjectiveTo investigate the effect of different extracts of Lysimachiae Herba on the main toxicity induced by Tripterygii Radix et Rhizoma.MethodNinety male SPF Kunming mice were randomly divided into 9 groups according to their body weight，control group， Lysimachiae Herba water extract group， Lysimachiae Herba 30% ethanol extract group， Tripterygii Radix et Rhizoma group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba water extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 30% ethanol extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 60% ethanol extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 95% ethanol extract group and Tripterygii Radix et Rhizoma combined with Lysimachiae Herba ethyl acetate extract group. The dosage of Tripterygii Radix et Rhizoma and Lysimachiae Herba were 2，1 g·kg-1 based on crude drugs， respectively. The control group was given an equal volume of solvent， and each group was given by gavage for 14 consecutive days. The blood and liver tissues were taken 24 hours after the last administration. The enzyme linked immunosorbent assay （ELISA） was used to detect serum biochemical indexes and liver lipid peroxidation/antioxidant indexes in mice. Meanwhile， principal component analysis was used to evaluate the attenuating effect and the mechanism of Lysimachiae Herba extract on toxicity of Tripterygii Radix et Rhizoma.ResultCompared with control group， Tripterygii Radix et Rhizoma caused the levels of alanine aminotransferase（ALT），aspartic acid amino transferase（AST），alkaline phosphatase（ALP） in serum of mice， and the levels of malondialdehyde （MDA） in liver， and comprehensive score of toxicity （Z value） produced by the above four indexes increased significantly （P<0.01）. The levels of total superoxide dismutase （T-SOD），glutathione-peroxidase （GPX），glutathione-S transferase （GST） decreased significantly （P<0.01） in liver. Compared with Tripterygii Radix et Rhizoma group， after intervention with extracts of two solvents （water， 30% ethanol） of Lysimachiae Herba， the levels of serum ALT， AST， ALP and liver MDA were significantly decreased （P<0.05， P<0.01）， while the levels of liver T-SOD， GPX and GST were significantly increased （P<0.01）. After intervention with extracts of two solvents （60% ethanol， 95% ethanol） of Lysimachiae Herba， the levels of serum ALT， AST， ALP were significantly decreased （P<0.01）， and liver GPX levels were significantly increased （P<0.01）. After the intervention with ethyl acetate extract of Lysimachiae Herba， only the level of serum AST was significantly decreased （P<0.05） and the level of GPX was significantly increased （P<0.05）. After the intervention with extracts of different solvents （water， 30% ethanol， 60% ethanol， 95% ethanol， ethyl acetate） of Lysimachiae Herba， it can significantly reduce the comprehensive score of toxicity （P<0.01）. The overall decline rates of toxicity were 127.5%， 113.4%， 98.1%， 56.3% and 31.0% respectively. Among them， the toxicity reduction rate of the extracts with water as a solvent was 14.1%， 29.4%， 71.2%， 96.5% higher than those of other solvent extracts with ethanol.ConclusionThe extracts of different solvents （water， 30% ethanol， 60% ethanol， 95% ethanol and ethyl acetate） of Lysimachiae Herba can reverse the toxicity induced by Tripterygii Radix et Rhizoma in varying degrees. Among them， water and 30% ethanol are the best solvents for detoxification， especially water as the extraction solvent， and with the increase of ethanol content or fat solubility of extraction solvent， the detoxification shows a downward trend.
Keywords：water extract of Lysimachiae Herba;30% ethanol extract of Lysimachiae Herba;comprehensive index;extraction solvent optimization;toxicity;Tripterygii Radix et Rhizoma
Abstract：ObjectiveThis study aims to investigate the effect of triptonide （TN） on proliferation， cell cycle， apoptosis and expressions of apoptosis-related proteins of human acute monocytic leukemia（AML） cell line SHI-1， and to explore its possible mechanism of action.MethodThe thiazolyl blue （MTT） colorimetric assay was applied to detect the inhibitory effect of 20，40，80，160，320 nmol·L-1 triptonide on the proliferation of SHI-1 cells for 48， 72 h. Changes in SHI-1 cell cycle before and after triptonide treatment were detected by flow cytometry propidium iodide （PI） simple staining， and changes in SHI-1 cell apoptosis before and after triptonide treatment were detected by flow cytometry with AnnexinV/PI double staining. Western blot was applied to detect the protein expression of cysteine protease （Caspase）-3， Caspase-8 and nuclear transcription factor kappaB（NF-κB） in SHI-1 cells before and after treatment with 80， 160 nmol·L-1 triptonide.ResultCompared with the blank group， 40，80，160，320 nmol·L-1 triptonide significantly inhibited the proliferation of SHI-1 cells（P<0.01） in a dose-dependent manner for 48， 72 h， while 160， 320 nmol·L-1 triptonide induced apoptosis of SHI-1 cells（P<0.01） for 48， 72 h， and 160 nmol·L-1 triptonide could decrease the S phase ratio of SHI-1 cells（P<0.01）. In addition， compared with the blank group， 80，160 nmol·L-1 triptonide induced the downregulation of NF-κB significantly（P<0.01）， 160 nmol·L-1 triptonide induced the downregulation of Caspase-3， Caspase-8 significantly（P<0.01）.ConclusionTriptonide can inhibit the proliferation and induce apoptosis in vitro of SHI-1 cells， which may be related to the reduction of the cells in S phase proportion by triptonide， and the downregulation of the expression levels of Caspase-3， Caspase-8 and NF-κB proteins.
Abstract：ObjectiveThe hypoglycemic effects and mechanisms of total flavonoids from Potentillae Discoloris Herba（TFE） on insulin resistance through the phosphatidylinositol-3 kinase （PI3K）/protein kinase B （Akt） signaling pathway in db/db mice were investigated.MethodThe 24 db/db mice were randomly divided into four groups， model group， metformin group and TFE 100，400 mg·kg-1 group respectively. The 6 db/m mice as normal control group. After 4 weeks treatment， the mice were processed and the levels of fasting blood glucose（FBG）， glycated serum protein（GSP），fasting blood insulin（FINS），triglyceride（TG）， total cholesterol（TC）， low density lipoprotein cholesterol （LDL-C），high density lipoprotein cholesterol （HDL-C） in serum were detected. Homeostatic model assessments of insulin resistance（HOMA-IR）were quantified. Hematoxylin-eosin（HE）staining of liver and pancreatic tissues were examined. The expression of IRβ， IRS-1，PI3K，phosphorylation-PI3K （p-PI3K）， Akt， phosphorylation-Akt（p-Akt） and glucose transporter 4（GLUT4） in livers were assessed by Western blot.ResultCompared with normal group， model group showed liver and pancreas injury. FBG， GSP， TC， TG， LDL-C， FINS and MDA levels in serum were significantly increased （P<0.01）， HDL-C and SOD levels in serum were significantly decreased （P<0.05）， liver glycogen content was significantly decreased （P<0.01）， as well as expression of IR， IRS-1， p-PI3K/PI3K， p-Akt/Akt and GLUT4 protein in liver tissues were significantly decreased （P<0.01）. Compared with model group， TFE was able to relieve liver and pancreas injury，while the levels of FBG， GSP， TC， TG， FINS and MDA in serum were significantly decreased （P<0.05）， HDL-C and SOD levels liver were significantly increased （P<0.05）， liver glycogen content was significantly increased （P<0.01）， and the expressions of IRS-1， p-PI3K/PI3K， p-Akt/Akt and GLUT4 protein in liver tissues were significantly up-regulated （P<0.05）.ConclusionThese findings indicate that TFE has the potential to reduce blood sugar and alleviates insulin resistance through the PI3K/Akt signaling pathway in the livers of db/db mice.
Keywords：total flavonoids from Potentillae Discoloris Herba extracts;db/db mice;type 2 diabetes mellitus;glucolipid metabolism;phosphatidylinositol-3 kinase （PI3K）/protein kinase B （Akt）
Abstract：ObjectiveTo evaluate the analgesic effects of Wenjing Zhitong prescription （WZP） and explore its possible analgesic mechanisms so as to provide experimental basis for research and development of new Chinese medicine.MethodAnalgesic effects of WZP were evaluated by observing the writhing latency and number in the writhing models which were induced by oxytocin in rats as well as those induced by acetic acid and prostaglandin E1 （PGE1）， respectively in mice. Effect of WZP on uterine contraction frequency， amplitude and activity were evaluated by observing the oxytocin-induced contraction of uterine smooth muscle in rats and rabbits in vivo. In the oxytocin-induced rat writhing models， the content of prostaglandin F2α （PGF2α） and prostaglandin E2 （PGE2） in rat uterine tissues and the content of beta-endorphins （β-EP） in rat serum were detected by enzyme-linked immunosorbent assay （ELISA）. Expression of estrogen receptor （ER） and oxytocin receptor （OTR） in rat uterine were tested by Real-time polymerase chain reaction（Real-time PCR） method to investigate the possible molecular mechanism of WZP for its analgesic effect.ResultResults of analgesic effect showed that in oxytocin-induced rat writhing experiment， the number of writhing responses in both the WZP （1.5，3.0 g·kg-1） group was lower than than in the model group （P<0.05）. In acetic acid-induced mice writhing experiment， the latency of writhing response in WZP （6.0 g·kg-1） group was significantly prolonged as compared with that in model group （P<0.01）， and the number of writhing response was significantly reduced （P<0.05）. In PGE1-induced mice writhing model， the writhing number in WZP （1.5，3.0，6.0 g·kg-1） groups was significantly lower than that in the model group （P<0.05，P<0.01）. Results of effect on uterine smooth muscle demonstrated that WZP （0.38，0.75，1.50 g·kg-1） could significantly reduce the frequency of uterine smooth muscle contraction in rabbits （P<0.05，P<0.01）， WZP （0.75，1.50，3.00 g·kg-1） could significantly reduce the contractile amplitude and activity of smooth muscle in the uterus of rats （P<0.05）. Results of molecular mechanisms of analgesic effects showed that the WZP （0.75，1.50，3.00 g·kg-1） significantly reduced the content of PGF2α and the ratio of PGF2α to PGE2 in the uterine tissue of rats （P<0.01）. In the WZP （3.00 g·kg-1） group， the levels of β-EP in the serum of rats were significantly increased （P<0.01）， and the levels of OTR in uterus of rats in the WZP （1.50，3.00 g·kg-1） group were significantly decreased （P<0.05）.ConclusionPharmacological studies demonstrated potent analgesic effect of WZP， and such analgesic effect were mediated by significantly inhibiting contraction of uterine smooth muscle， decreasing the contents of PGF2α and ratio of PGF2α/PGE2， reducing OTR expression in uterine as well as increasing the amount of β-EP in serum.
Keywords：Wenjing Zhitong prescription;primary dysmenorrhea;pharmacodynamics;mechanisms of actions
Abstract：ObjectiveTo explore the regulatory effect of Siwu paste on the bone marrow hematopoietic function of aplastic anemia （AA） model rats.MethodSD rats were randomly divided into normal control group， model group， positive drug （Fufang E'jiao Jiang 10.8 g·kg-1） group， high-dose Siwu paste （22.68 g·kg-1） group and low-dose Siwu paste （5.67 g·kg-1） group. Acetophenazine （APH） combined with cyclophosphamide （CTX） injection was used to establish the aplastic anemia rat model. The administration groups were given the corresponding drugs （ig） for 15 consecutive days. The levels of white blood cells （WBC）， red blood cells （RBC）， hemoglobin （HGB）， hematocrit （HCT） and platelets （PLT） in peripheral blood cells of rats were detected， thymus and spleen indexes were calculated and compared. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-3 （IL-3） and interleukin-6 （IL-6） in rat serum. The pathological changes of bone marrow were observed by hematoxylin eosin （HE） staining. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） methods were used to detect Toll receptor 4 （TLR4） and nuclear transcription factor-κB （NF-κB） protein and gene expression in rat femoral bone marrow cells.ResultCompared with the normal control group， the WBC， RBC， HGB， HCT and PLT levels of the model group were significantly reduced， the thymus index was significantly decreased， the spleen index was significantly increased， the serum IL-3 level was significantly decreased， and the IL-6 level was significantly increased. The number of neutrophils and megakaryocytes in the femoral bone marrow was reduced， and the medullary cavity was filled with edema fibrofatty tissue. The expressions of TLR4 and NF-κB protein and mRNA in bone marrow cells were significantly increased （P<0.01）. Compared with the model group， the levels of WBC， RBC， HCT and PLT in peripheral blood cells of rats in the high-dose Siwu paste group increased， the thymus index increased， the spleen index decreased， the IL-3 level was significantly increased， the IL-6 level was significantly decreased， the pathological morphology of femoral bone marrow was slightly improved， and the expressions of TLR4 and NF-κB protein and mRNA in bone marrow cells decreased significantly （P<0.05， P<0.01）.ConclusionSiwu paste may improve the bone marrow hematopoietic function of rats with aplastic anemia by regulating the expression of the bone marrow inflammation signal pathway TLR4/NF-κB.
Abstract：ObjectiveThis study aims to evaluate the clinical effect of Changyanqing mixture combined with mesalazine enteric-coated tablets in the maintenance treatment of ulcerative colitis（UC） in remission period.MethodThe 140 patients with UC in remission period were randomly divided into control group （70 cases） and observation group （70 cases）. The 61 patients in control group completed the therapy （6 cases lost or lost to follow-up and 3 were eliminated）， 63 patients in observation group completed the therapy （5 cases lost or lost to follow-up and 2 were eliminated）. Both groups′ patients got treatment of lifestyle adjustment， and they also took mesalazine enteric-coated tablets orally， 0.5 g/time， 3 times/day. Patients in observation group took Changyanqing mixture orally for a month in the morning and evening every day， 150 mL/time， and then changed to 150 mL/time， 1 time/day， for 3 consecutive months， finally changed to once every other day for 8 months. Patients in control group took simulated medicine of Changyanqing mixture orally in the same way as observation group. The treatment was continued for 12 months. When UC recurred during the treatment， patients took mesalazine enteric-coated tablets orally at 1 g/time， 3 times/day until remission， when the above intervention plan was continued to be adopted. The recurrence rate， first recurrence time within 12 months （duration from remission to Mayo≥3） and the degree of disease activity at recurrence were recorded. Scores of traditional Chinese medicine（TCM）syndrome and inflammatory bowel disease questionnaire （IBDQ） were evaluated once every 2 months. Before treatment， and at the 6th and 12th month after treatment， colonoscopy and mucosal histology were performed once， enteroscopic mucosal scores， Geboes index of mucosal histology were evaluated， and fecal calprotectin（FC） levels were detected. Also， safety evaluation was conducted.ResultDuring 12 months， the recurrence rate in observation group was 20.63% （13/63）， lower than 39.34% （24/61） in control group（P<0.05）， the frequency of recurrence and the first recurrence duration in observation group were all less than those in control group（P<0.01）. All these meant the disease activity of patients in observation group was lighter than that in control group （=5.947， P<0.05）. After repeated measurements of variance analysis， scores of TCM syndrome， enteroscopic mucosal scores， Geboes index and FC levels in two groups gradually increased（P<0.05）， and scores of IBDQ gradually decreased （P<0.05） during the 12-month period. At the second， fourth， sixth， eighth， tenth and twelfth month， scores of TCM syndromes in observation group were lower than those in control group （P<0.01）， and scores of IBDQ were higher than those in control group （P<0.01）. At the sixth and twelfth month after treatment， intestinal endoscopic mucosal scores， Geboes index and FC levels in observation group were all lower than those in control group （P<0.01）. And there were no adverse reactions related to Changyanqing mixture.ConclusionChangyanqing mixture combined with mesalazine enteric-coated tablets in the maintenance treatment of patients with UC in remission can control the FC level， further reduce the recurrence rate， delay the recrudescence-time， reduce the frequency of UC and the disease activity， maintain the good remission state of UC， stabilize the quality of life of patients， and ensure the safety of clinical use.
Abstract：ObjectiveThis study aims to investigate the clinical efficacy of modified Anshentang on the treatment of ankylosing spondylitis in early and middle stages with kidney deficiency and cold-governing syndrome and its effect on serum inflammatory factors， immune function， and bone metabolism indexes of patients.MethodIn this study， 120 patients were randomly divided into control group and observation group， 60 cases in each group. On the basis of ethotrexate treatment， patients in control group took Bushen Shuji granule orally， while patients in observation group took modified Anshentang orally for 8 weeks. Before and after treatment， patients in two groups were observed for clinical symptoms ［ bath ankylosing spondylitis patient global score （BAS-G）， bath ankylosing spondylitis disease activity index （BASDAI）， spondyloarthritis research consortium of Canada （SPARCC）， traditional Chinese medicine symptoms （TCM symptoms） ］， serum inflammatory factors ［ tumor necrosis factor-α （TNF-α）， macrophage migration inhibitory factor （MIF）， interleukin-23 （IL-23）］， immune function ［ immunoglobulin A（IgA）， immunoglobulin G（IgG）， immunoglobulin M（IgM）］， bone metabolic indicators ［osteocalcin （BGP）， bone morphogenetic protein-2 （BMP-2）， bonespecific alkaline phosphatase （BALP）］. The clinical efficacy， adverse reactions and recurrence rates of 12 months in two groups were observed.ResultDuring the study， 4 cases dropped out from control group and 2 cases from observation group. The total effective rate of 96.55% （56/58） in observation group was higher than 80.36% （45/56） in control group （χ2=4.827，P<0.05）. The recurrence rate of 5.17% （3/58） in observation group was lower than 19.64% （11/56） in control group （χ2=5.187， P<0.05）. Compare with control group after treatment， BAS-G，BASDAI， SPARCC， TCM symptoms， TNF-α， MIF and IL-23 in observation group were significantly decreased （P<0.05）， while BGP， BMP-2， BALP， IgA， IgG and IgM were significantly increased （P<0.05）. The incidence of adverse reactions was 12.07%（7/58） in observation group， which was lower than 32.14%（18/56） in control group （χ2=4.826，P<0.05）.ConclusionModified Anshentang is effective in the treatment of ankylosing spondylitis in early and middle stages with kidney deficiency and cold-governing syndrome， and the incidence of adverse reactions is low.
Keywords：modified Anshentang;ankylosing spondylitis;inflammatory factors;immune fuction;bone metabolism index
Abstract：ObjectiveTo observe theclinical efficacy of modified Banxia Baizhu Tianmatang combined with acupuncture on migraine with wind phlegm disturbance syndrome， and the regulatory effect on neurovasoactive peptide and vascular endothelial activator.MethodTwo hundred and fifty patients were randomly divided into control group （75 cases） and observation group （75 cases）. Patients in Two group got acupuncture for 6 times， 1 time/day， after a day of rest， they got placebogranules of Banxia Baizhu Tianmatang， 10 g/time， 2 times/day. Patients in observation group got Banxia Baizhu Tianmatang， 1 dose/day， and also the same acupuncture with the therapyof control group. And the treatment lasted for 4 weeks. At the half， 1st， 2nd， 6th， 12th， 24th， and 48th hour after treatment， VAS were scored， rate of pain relief within 6， 12， and 24 hours， disappearance rate and recurrence rate of pain within 72 hours， migraine attack times， headache duration and headache degree before 4 weeks of treatment， during the treatment and after the treatment were recorded. Before and after treatment， accompanying symptoms， wind phlegm disturbance syndrome， headache impact test version-6 （HIT-6） and the migraine disability assessment questionnaire （MIDAS） were scored. And levels of calcitonin gene-related peptide （CGRP）， nitric oxide （NO）， endothelin-1 （ET-1）， pituitary adenylate cyclase activating peptide （PACAP）， S100B protein， substance P（SP）， von Willebrand factor （vWF） and fibrinogen （FIB） were detected. And safety was evaluated.ResultVAS in two groups decreased at different time points （P<0.01）， and VAS in observation group at 6th， 12th， 24th and 48th hour after treatment were lower than those in control group （P<0.01）. The rate of pain relief in observation group at 6th and 12th hours after treatment and the disappearance rate of pain at 72th hour were 67.14%（47/70）， 87.14% （61/70） and 92.86% （65/70）， which were higher than 50.00% （34/68）， 70.59% （48/68） and 79.41% （54/68） in control group. The recurrence rate of pain in observation group was 21.43% （15/70）， which was lower than 39.71% （27/68） in control group （P<0.05）. During the treatment and drug withdrawal， times of migraine attack， headache duration and headache degree were all less than those in control group （P<0.01）. Scores of accompanying symptoms， wind phlegm disturbance syndrome， HIT-6 and MIDAS were all lower than those in control group （P<0.01）. The clinical effect was better than that in control group （Z=2.106， P<0.05）. Levels of CGRP， PACAP， S100B protein， SP， ET-1， vWF and FIB were lower than those in control group， while level of NO was higher than control group （P<0.01）.ConclusionModified Banxia Baizhu Tianmatang combined with acupuncture had a better instant analgesic effect， with a significant effect on continuing analgesia and reducing headache recurrence. It can also alleviate migraine symptoms and accompanying symptoms， andreduce the impact of migraine on daily life and the degree of disability. Its mechanism may be related to the regulation of neurovasoactive peptides and vascular endothelial substances. It is worth for further study.
Abstract：ObjectiveTo observe the clinical efficacy of modified Banxia Xiexintang on nonalcoholic fatty liver （NAFLD） and the regulatory effect on insulin resistance （IR）.MethodOne 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 β cell function index （HOMA-β） 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）-α and interleukin-6 （IL-6） were detected. And the safety was evaluated.ResultCAP and HOMA-IR in observation group were lower than those in control group after treatment and during the follow-up （P<0.01）， and ISI and HOMA-β were higher than those in control group （P<0.01）. Amelioration of indexes of blood lipid was better than those in control group （P<0.01）. Levels of ALT， AST， FBG and FINS were lower than those in control group （P<0.01）. Scores of traditional Chinese medicine （TCM） syndromes were lower than those in control group （P<0.01）， ratio of liver/spleen CT and adiponectin was higher than that in control group （P<0.01）. Levels of TNF-α， IL-6， vaspin and leptin were lower than those in control group （P<0.01）. B-ultrasound efficacy and fat content of liver were superior to those of control group （P<0.05）. There were no serious adverse events and drug-related adverse reactions.ConclusionModified Banxia Xiexintang can regulate glucose and lipid metabolism， improve insulin sensitivity and HOMA-β 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.
Keywords：nonalcoholic steatohepatitis;disharmony of liver and stomach;stagnation of dampness and turbidity;Banxia Xiexintang;insulin resistance;HOMA-β cell;adipocyte factor
Abstract：ObjectiveTo observe the short-term effect of modified Kaijie Huatantang on chronic rhinosinusitis with nasal polyp due to qi stagnation phlegm syndrome.MethodA total of 90 cases were divided into control group and observation group，with 45 cases in each group. The control group was given mometasone furoate，and the observation group was given modified Kaijie Huatantang after nasal endoscopy surgery for 4 weeks. After treatment and follow-up for 1 years，the sino-nasal outcome test-20（SNOT-20），Lund-Kennedy and traditional Chinese medicine（TCM） syndrome were observed. The serum and nasal secretions tumor necrosis factor-alpha（TNF-α），interleukin（IL）-1β，IL-8，IL-17，eosinophilic cationic protein（ECP） and immunoglobulin E（IgE） were detected before and after treatment. The safety，clinical efficacy after treatment and follow-up for 1 years were compared between two groups.ResultAfter treatment and follow-up for 1 years，the total control rates were 97.7%，93.0% in observation group， which were higher than 87.8%，75.6% in control group（P<0.05）. Compared with the control group after treatment and follow-up for 1 years，SNOT-20，Lund-Kennedy and TCM syndrome scores in the observation group decreased in the same period（P<0.05）. Compared with the control group after treatment，the serum and nasal secretions TNF-α，IL-1β，IL-8，IL-17，ECP and IgE in the observation group were significantly decreased（P<0.05）. The incidence of postoperative complications was 2.3% in the observation group， which was lower than 17.1% in the control group（P<0.05）. The incidence of adverse reactions was 4.7% in the observation group， which was lower than 41.5% in the control group（P<0.05）.ConclusionModified Kaijie Huatantang can significantly improve the short-term clinical efficacy of patients with chronic rhinosinusitis and nasal polyp due to Qi stagnation phlegm obstruction，with a low incidence of adverse reactions.
Abstract：ObjectiveTo study the clinical efficacy of Chaihu Shugansan on non-alcoholic fatty liver（NAFLD） patients with liver stagnation and spleen deficiency syndrome and its effect on intestinal flora.MethodThe study was a single-center， randomized，single-blind， placebo-controlled clinical study involving 80 patients with NAFLD treated from January 2019 to January 2020 at our hospital. They were divided into two groups （Chaihu Shugansan group，n=40） and control group （placebo group，n=40）. The two groups of patients were given lifestyle intervention as the basic protocol. The treatment group was orally given Chaihu Shugansan，and the control group was orally given placebo. The drugs were given twice in the morning and evening， 1 dose/time. Patients were followed up for 12 weeks. Before and after treatment，the efficady on liver steatosis was observed by abdominal ultrasound and transient elastography （Fibroscan）， levels of alanine aminotransferase（ALT），aspartate aminotransferase（AST），glutamyl transpeptidase（γ-GT），high density lipoprotein cholesterol（HDL-C），low density lipoprotein cholesterol（LDL-C），total cholesterol（TC），triglyceride（TG），interleukin（IL）-6，IL-1β，Toll-like receptor-4（TLR-4） in peripheral blood mononuclear cells（PBMCs） and intestinal flora were also detected.ResultThere were 37 patients in the treatment group and 35 patients in the control group who finally completed the study protocol. The total effective rate of NAFLD in the treatment group（81.08%，30/37） was higher than that in the control group （68.57%，24/35）（Z=2.67，P<0.05）. The treatment group was superior to the control group in reducing the levels of BMI，ALT，AST，TC，LDL-C，TG，γ-GT and increasing the level of HDL-C（P<0.05）. The levels of pro-inflammatory cytokines（TNF-α，IL-1β and IL-6），the values of Controlled Attenuation Parameter（CAP），Liver Stiffness Measurement（LSM） and expression of TLR4 were down-regulated in the treatment group （P<0.01）. In addition，the treatment group showed increase in the abundance of beneficial bacteria （Bifidobacterium and Lactobacillus） and inhibited the abundance of pathogenic bacteria （Enterobacter and Enterococcus） in the gut（P<0.01）.ConclusionIn addition to the lifestyle intervention，Chaihu Shugansan can improve lipid metabolism and liver function，regulate intestinal flora and inhibit the level of inflammatory factors in patients with NAFLD.
Abstract：ObjectiveTo analyze the chemical constituents in Microctis Folium by ultra performance liquid chromatography-quadrupole-time-of-flight high resolution mass spectrometry （UPLC-Q-TOF-MS/MS）.MethodWaters CORTECS UPLC C18 column （2.1 mm×150 mm， 1.6 μm） was used for chromatographic separation with the mobile phase of methanol （A） -0.1% formic acid solution （B） for gradient elution （0-4 min， 14%-30%A； 4-16 min， 30%-58%A； 16-25 min， 58%-78%A； 25-25.1 min， 78%-98%A； 25.1-29 min， 98%A）， the flow rate was 0.25 mL· min-1， the injection volume was 1 μL. The electrospray ionization （ESI） was adopted for determining the chromatographic effluent under positive and negative ion modes， the main chromatographic peaks were assigned and distinguished by Q-TOF， and the scanning range was m/z 100-1 500.ResultA total of 31 chemical constituents in Microctis Folium were identified by confirmation of reference substances， literature comparison and high resolution mass spectrometry data analysis. The chemical constituent cluster was composed of 28 flavonoids （9 flavone C-glycosides， 10 flavonols and their glycosides， 8 proanthocyanidins， 1 xanthone） and 3 organic acids （caffeic acid， p-coumaric acid， ferulic acid）.ConclusionUPLC-Q-TOF-MS/MS technique provides a simple， rapid and accurate method for the identification of chemical constituents in Microctis Folium. Flavone C-glycosides， flavonol oxyglycosides and proanthocyanidins are the main chemical constituents. The 7 proanthocyanidins are reported for the first time in this herb. In conclusion， the chemical profile of Microctis Folium is characterized and the findings are meaningful for the in-depth quality assessment and material basis clarification of Microctis Folium.
Keywords：Microctis Folium;ultra performance liquid chromatography-quadrupole-time-of-flight high resolution mass spectrometry （UPLC-Q-TOF-MS/MS）;chemical constituents;flavone C-glycosides;flavonol oxyglycosides;proanthocyanidins;organic acids
Abstract：ObjectiveTo investigate the factors affecting the quality of post-harvest Angelicae Dahuricae Radix （Baizhi） and to provide the corresponding suggestions according to these factors.MethodA series of factors affecting the quality of Baizhi were analyzed comprehensively by visiting several origins， medicinal material markets， pharmacies， supermarkets and storehouses combined with plenty of literature reports.ResultThe rot of Baizhi was the most common phenomenon after harvest， and mildew， discoloration and moth could occur during the processes of processing， storage and packaging. So the quality of Baizhi should be controlled strictly through the whole process. The roots of Baizhi should be harvested on sunny days to avoid mining damage and dried as soon as possible to prevent rotting. The drying methods included both traditional lime burial and modern ways such as sulfur fumigation， saline dehydration， sun drying method， and oven drying method. However， the water content should be strictly controlled. Furthermore， the storehouses should be disinfected firstly. The temperature and humidity of the storehouses should be controlled strictly. Some suitable ways could be adopted to prevent moth and discoloration during storage， which included airtight fumigation of aluminum phosphide， cold storage， air conditioning maintenance， antagonism storage with other Chinese medicinal materials， dry ice storage at room temperature， etc. Large quantities of Baizhi were generally packaged in woven bags. Otherwise， kraft paper bags， polyvinyl chloride plastic bags， glass bottles， aluminum foil composite film bags， and other packaging materials had been adopted for the retail. However， the packaging specification should be selected according to the situation.ConclusionThe quality of Baizhi can be directly affected by harvesting， drying， processing， storage and packaging. Scientific and reasonable methods should be adopted to ensure the quality of Baizhi.
Abstract：ObjectiveTo study the change of soil environment and yield of Angelica sinensis when cultivated on the film side and and open field sides，and to explore the influence of garlic volatiles and film-side cultivation on continuous cropping A. sinensis，so as to provide some certain theoretical basis for the saying that the A. sinensis garlic intercropping mode and film-side cultivation could alleviate continuous cropping A. sinensis.MethodIn this study， the effects of garlic on soil environment and yield of A. sinensis cultivated on film side and crop rotation were discussed through the determination and analysis of soil microorganism quantity，soil enzyme activity and yield of Angelica sinensis in the rhizosphere of A. sinensis.ResultThe number of bacteria and actinomycetes in the rhizosphere soil of A. sinensis increased significantly， while the number of fungi decreased significantly. Among them， the number of bacteria and actinomycetes in the intercropping of A. sinensis and garlic on the film side increased by 104% and 146.89% on average as compared with that of the control （monoculture under continuous cropping open field），and the number of fungi decreased by 39.28% on average as compared with that of control group. When the enzyme activity in the rhizosphere soil was significantly increased under the condition of intercropping with garlic on the film side，the soil urease，sucrase，alkaline phosphatase and acid phosphatase activities under the intercropping of A. sinensis and gralic on the rotation film side were increased by 61.60%，51.09%，203.48% and 76.19% respectively as compared with those in control group. The yield of A. sinensis significantly increased under the condition of intercropping with garlic on the film-side，and the yield of Angelica sinensis under the rotation film-side intercropping with garlic increased by 39.37% as compared with that of control group.ConclusionUnder the mode of film-side cultivation，the interplanting of A. sinensis with garlic can change the number of soil microorganism，improve the activity of soil enzyme，improve the physical and chemical properties of soil， alleviate the obstacle of continuous cropping and guarantee the healthy growth of A. sinensis more effectively.
Keywords：film-side cultivation;intercropping garlic;soil microbial quantity;soil enzyme activity;yield of Angelica sinensis
Abstract：ObjectiveTo study the mechanism of astragaloside Ⅳ in the treatment of ischemic stroke by means of network pharmacology.MethodThe targets of astragaloside Ⅳ were predicted using Swiss Target Prediction platform， and the targets of ischemic stroke were retrieved using GeneCards， Therapeutic Target Database （TTD）， Traditional Chinese Medicine Integrated Database （TCMID） and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） databases. The potential targets of astragaloside Ⅳ acting on ischemic stroke were obtained by the intersection of the targets of astragaloside Ⅳ and ischemic stroke. STRING platform was used to build protein-protein interaction （PPI） network， and eigenvalues were calculated through network topology analysis to screen core targets. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were performed on the related targets in DAVID database. Finally， molecular docking verification was conducted to further clarify the core targets of astragaloside Ⅳ acting on ischemic stroke.ResultThe 44 common targets were obtained after the intersection of the targets of astragaloside Ⅳ and ischemic stroke. PPI network topology analysis showed that RAC-alpha serine/threonine-protein kinase （Akt1）， renin （REN）， epidermal growth factor receptor （EGFR）， vascular endothlial growth factor A （VEGFA） and neuronal proto-oncogene tyrosine-protein kinase （SRC） were the core targets of astragaloside Ⅳ in the treatment of ischemic stroke. Enrichment analysis results of KEGG pathway showed that the pathways of astragaloside Ⅳ acting on ischemic stroke involved the neuroactive ligand-receptor interaction pathway， cGMP-PKG signaling pathway， calcium signaling pathway， Rap1 signaling pathway， PI3K/Akt signaling pathway， etc.ConclusionAstragaloside Ⅳ may promote angiogenesis and inhibit platelet activity by acting on Akt1， REN， EGFR， VEGFA， SRC， thus improving cerebral blood flow. It can also inhibit the apoptosis of ischemic brain tissue cells and inflammation to reduce the damage of nerve function， and finally treat ischemic stroke. This study provides ideas and guidance for further exploring the mechanism of astragaloside Ⅳ in the treatment of ischemic stroke.
Abstract：ObjectiveThis research aims to construct the "disease-gene-target-components-drug" network with the methods of network pharmacology and bioinformatics， and to explore the key genes and signaling pathways of Xiao Qinglongtang in the treatment of bronchial asthma.MethodFirst，we selected the differentially expressed genes between patients with asthma and healthy people with use of the gene expressing Omnibus（GEO） database，and searched the active ingredients from Xiao Qinglongtang with use of TCMSP database，and then screened disease genes and herb ingredient targets as intersecting genes to construct the protein-protein interactions （PPI） network by using R language and Cytoscape 3.7.2 software. At the same time Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out.ResultSeries GSE43696 in GEO database were successfully filtered，which contained 108 pieces of chip data. A total of 820 differentially expressed genes were screened from the chip data. Then we filtered 169 active ingredients and 246 targets of Xiao Qinglongtang from database. Through the above steps，we obtained 25 intersecting genes， and PPI network results showed that 91 potential targets may be involved in the mechanism of Xiao Qinglongtang. A total of 180 gene functions such as response to oxidative stress，inflammatory response，extracellular matrix organization and positive regulation of vascular endothelial growth factor production were showed in GO enrichment analysis results. 39 signaling pathways were showns in the results of KEGG pathway enrichment analysis，such as T helper cell 17（Th17） cell differentiation，interleukin 17（IL-17）signaling pathway，tumor necrosis factor（TNF） signaling pathway，and hypoxia inducible factor-1（HIF-1） signaling pathway.ConclusionXiao Qinglongtang fully embodies the characteristics of multi-components，multi-targets and multi-pathways in the intervention of bronchial asthma. The results of the study could provide an important basis for mechanism research of Xiao Qinglongtang in treating asthma.
Abstract：ObjectiveTo systematically evaluate the clinical efficacy of Tanreqing injection in the treatment of elderly chronic bronchitis.MethodCBM，CNKI，WanFang Data，VIP，PubMed，The Cochrane Library，Embase and other databases were retrieved by computer to screen out randomized controlled trials of Tanreqing injection in the treatment of elderly chronic bronchitis. The retrieval time was from the establishment to December 2019. After two researchers independently screened out the literatures according to the inclusion and exclusion criteria，extracted data and evaluated the literature quality，made meta-analysis using RevMan 5.3 software，and performed Egger test by Stata 14.0 software to evaluate publication bias. In case of any publication bias，clipping and supplementation method was further used to evaluate the effect of bias on the results.ResultA total of 48 studies were included，including 4 356 patients with diabetic nephropathy. The results of Meta-analysis showed that compared with conventional antibiotic therapy，the group of combination with Tanreqing injection was better than the control group in effective rate and lowering serum c-reactive protein （CRP） level，with statistically significant differences. The results of the publication bias test showed that a developmental bias in the effective rate. Further analysis based on the non-parametric clipping and supplementation method showed stable results of meta-analysis and no impact from potential publication bias. The adverse reactions had no statistically significance.ConclusionThis study shows that Tanreqing injection has a significant effect in treating chronic bronchitis in the elderly，and can reduce the serum CRP level of the patients. Compared with the conventional therapy group，the incidence of adverse reactions is not significantly increased，and the results need further clinical tests.
Keywords：Tanreqing injection;chronic bronchitis in the elderly;Meta-analysis
Abstract：ObjectiveThe Meta-analysis was used to systematically evaluate the clinical efficacy of traditional Chinese medicine in treating Late onset hyponatremia （late onset hyponatremia，LOH）.MethodPubmed，Web of Science，China Knowledge Base Database （CNKI），Wanfang Database （WanFang），Weipu Full-text Periodical Database（VIP），Chinese Biomedical Literature Database （CBM）were retrieved to collect randomized controlled trials of traditional Chinese medicine（TCM） for treatment of LOH. Two researchers independently screened out the literatures， extracted the data， conducted quality assessment by Cochrance bias risk assessment tool，and made Meta-analysis by RevMan 5.3.5 software.ResultNine eligible documents were finally included. Meta-analysis results showed that the test group was superior to the control group in improving patient's physical fitness/cardiovascular score ［mean deviation（MD）=-1.42，95% CI（-2.39，-0.45），P=0.004］ and psycho-psychological score［MD=-0.74，95% CI（-1.26，-0.22），P=0.005］，with no statistically significant difference between test group and control group in sexual function score ［MD=-0.68，95% CI（-1.38，-0.03），P=0.06］，serum testosterone （TT） concentration［MD=-0.68，95% CI（-1.38，-0.03），P=0.06］ and effective rate ［odds ratio（OR）=1.57，95% CI（0.64，3.88），P=0.33］.ConclusionTCM is equivalent to western medicine（testosterone undecanoate）in the treatment of late onset hypogonadism， and better than western medicine in improving patients' physical fitness/cardiovascular score and mental and psychological score.
Keywords：late onset hyponatremia;male menopause syndrome;randomized controlled trial;traditional Chinese medicine;Meta-analysis
Abstract：Qingjin Huatanpang， first contained in Yixue Tongzhi， was composed of eleven medicinal materials of Scutellariae Radix， Gardeniae Fructus， Fritillariae Thunbergii Bulbus， Mori Cortex， Trichosanthis Semen Tostum， Citri Exocarpium Rubrum， Platycodonis Radix， Ophiopogonis Radix （core removed）， Anemarrhenae Rhizoma， Poria and Glycyrrhizae Radix et Rhizoma. It is a classic prescription created by YE Wen-ling in Ming dynasty for treating pulmonary disease with phlegm-heat obstructing lung syndrome. With the significant functions of clearing heat and moistening lung， reducing phlegm and relieving cough， it has been included in the "Classic Catalogue of Ancient Classics （First Batch）". Modern pharmacological studies have shown that Qingjin Huatantang has multiple activities such as relieving cough and eliminating phlegm， anti-inflammatory， bronchodilation， and immunoregulatory， and now it is commonly used for treating infectious lung diseases， such as acute exacerbation of chronic obstructive pulmonary disease， community acquire pneumonia， bronchiectasis， acute and chronic bronchitis in a form of its modified prescription or its combined use with western medicine， consistent with the clinical application in ancient times. According to the literatures on the study of Qingjin Huatantang published in recent years， this paper summed up the historical evolution， compatibility analysis， chemistry constituents， quality control， advances in pharmacology research， and clinical uses， which can provide theoretical and experimental data reference for further research and development， and proposed to establish a biological activity assay for quality control based on the pharmacological effect such as immunoregulatory activity， which can improve its quality control method and provide a reference for other famous classical formulas.
Keywords：Qingjin Huatantang;historical evolution;compatibility analysis;chemical constituents;pharmacology research;clinical uses;quality control
Abstract：Airway remodeling is an important pathological basis of asthma， and also the main reason for the difficulty in asthma therapy. By referring to the experimental reports on the treatment of airway remodeling in asthma with traditional Chinese medicine （TCM） in recent years， the authors comprehensively analyzed the effect of TCM on proteins related to airway remodeling in asthma， and it was found that TCM could regulate the signal pathway related proteins （such as transforming growth factor-β1/Smads， extracellular signal-regulated kinase and Wnt/β-catenin）， structural proteins （such as α-smooth muscle actin， collagen， osteopontin and fibrin） and gene regulatory proteins （such as matrix metalloproteinase-9， vascular endothelial growth factor， B lymphoma cell-2 related X protein）， and participate in the regulation of airway remodeling signaling pathway， tissue structure homeostasis and gene expression， so as to inhibit airway remodeling in asthma. In conclusion， TCM can improve the pathological morphology of airway remodeling and delay the progress of airway remodeling by controlling the corresponding proteins. At present， however， a lot of studies are limited to single Chinese herbal or TCM extract in animal experiments， and there is a lack of clinical research. It is suggested to establish a systematic and multi-level study on the mechanism of TCM for treating airway remodeling in asthma based on the theory of TCM， so as to provide a better reference for clinical practice.
Keywords：traditional Chinese medicine （TCM）;airway remodeling;asthma;signal pathways;tissue structure;gene expression;protein levels
Abstract：As a traditional Chinese medicine， Ziziphi Spinosae Semen （ZSS） has the functions of tonifying liver， tranquilizing heart， astringent sweat and producing body fluid， which is used to treat neurasthenia， insomnia， dreaminess， debility， night sweat and so on. With the rapid and constant development of ZSS resource industry and its medicinal value， a large number of by-products and waste generated in the production and processing process， resulting in serious environmental problems. In general， the utilization rate of ZSS resources was still not high. Based on this， the chemical components and potential resources of ZSS were systematically combed from the perspective of the medicinal parts and bioactive components in this paper， and the authors had summarized that the widely application of ZSS and its by-products （fruit， leaf， root， etc.） in the fields of food， medicine， functional food and other areas was discovered and summarized as feed， feed additives， activated carbon， organic fertilizer， etc. In addition， this paper systematically summarized the current environmental protection problems of the industry， and put forward suggestions for improvement， aiming at reducing environmental pollution and improving the utilization efficiency of resources， so as to provide reference and basis for the comprehensive utilization of ZSS and its by-products， and promote the green， economical and double-effect development of the industry.
Abstract：Based on theory of "paired relationship between the heart and the small intestine" in traditional Chinese medicine（TCM）， heart disease can affect the small intestine， and intestinal diseases can also affect the heart. The heart controls mental activities， so if the secretions function of small intestine is impaired， it will hinder the mind of the mind. Modern medicine has found that intestinal flora is closely related to cognitive function， which is consistent with the "paired relationship between heart and small intestine" in TCM. Diabetes cognitive impairment （DCI） is a category of "diabetes dementia" in TCM. According to TCM， the imbalance of spleen and stomach is the starting factor of diabetes dementia， and the phlegm turbidity of spleen deficiency is the pathological product of diabetes dementia. Previous projects have proved that intestinal flora disturbance is the modern pathological basis of spleen and stomach imbalance in TCM， suggesting that restoring spleen and stomach function to adjust intestinal microbial homeostasis is helpful for the prevention and treatment of diabetes dementia. At present， many achievements have been made in the study of the mutual causality between diabetes and intestinal flora disorder. In recent years， the incidence of DCI has increased rapidly， and the pathogenesis is complex and unclear， which increases the difficulty of treatment. Therefore， finding new targets should not be ignored. Given the complex connections among intestinal flora， diabetes and cognitive impairment， it is particularly important to tease out the relationship among the three. Based on previous scientific research， the author analyzed layer by layer and found that intestinal flora can not only affect the synthesis of neurotransmitters in the brain， but also participate in the common pathogenesis of diabetes and cognitive impairment such as chronic inflammation， insulin resistance and blood glucose rise， with a typical target effect. The pathogenic mechanism of intestinal flora in DCI was summarized in order to establish a new target and direction for the treatment， and to explore the scientific connotation of TCM in regulating spleen and stomach for treatment of diabetes dementia.
Keywords：intestinal flora;diabetes;cognitive impairment;heart;small intestine;traditional Chinese and Western medicine
Abstract：Diabetes has become one of the fastest growing public health issues in the world. Its pathological mechanism is complex and affected by multiple factors. There are trillions of microbes in the human intestine， which are roughly divided into three types： probiotics， neutral bacteria， and pathogenic bacteria. They are in a dynamic balance and constitute a complex intestinal micro-ecosystem. The balance and homeostasis of the intestinal micro-ecosystem are essential to maintain the stability of the body's environment and human health. With the rapid development of high-throughput sequencing technology， imbalanced intestinal flora distribution has been proven to be an important factor in promoting the development of insulin resistance （IR）， thus increasing the risk of diabetes. In recent years， the regulation of intestinal flora has become a new approach and new target for the prevention and treatment of diabetes and its complications. The application of traditional Chinese medicine （TCM） in treatment of metabolic diseases such as diabetes and obesity has a long history. TCM has its unique characteristics and advantages， however， the unclear mechanism of action has limited its modernization and industrialization. The harmonious symbiosis between the intestinal flora and the host is consistent with the TCM theory of "harmony between human and nature". The effect of TCM on the intestinal microflora has gradually become a hot topic in medical research today. One study believes that diabetes originates from "intestinal fever". At present， some relevant experimental researches and clinical research literatures have shown that some heat-clearing Chinese herbal compounds have a certain regulating effect on imbalanced intestinal flora. Therefore， the relationship between intestinal flora and diabetes was explored， and the mechanism of heat-clearing Chinese herbal compounds （Da Chaihutang， Gegen Qinliantang， Huanglian Jiedutang， and Wumeiwan） in preventing and treating heat syndrome of diabetes through regulation of intestinal flora was analyzed， in order to provide new theoretical basis and research clues for the further development of drugs for treating diabetes.
Abstract：With the development of economic globalization and the increasingly complex international competition environment， pharmaceutical research and development has become the most powerful weapon for pharmaceutical companies to cope with the uncertainty of the competitive market. From the perspective of the pharmaceutical industry， based on the five-element theory， the article used the thinking of comparative state to carry out analogy research on the five-element theory and entrepreneur type system. Based on the entrepreneur type system and enterprise management system， the article embedded the enterprise senior management team system， and entrepreneurs were included in the system and assigned roles according to their different characteristics. Then through the analysis of the relationship between different entrepreneurs and the research and development （R&D） directors， the article expounded the influence of different types of entrepreneurs on the R&D process. The purpose of this study is to provide different types of entrepreneurs with management solutions for pharmaceutical R&D innovation and internal collaborative management， which is conducive to the analysis of advantages and disadvantages of entrepreneurs based on their own characteristics， and can effectively improve their ability of internal resource integration and independent innovation in drug R&D.
Keywords：five-element theory;entrepreneurs;drugs;research and development innovation;comparative state;mutually reinforce and neutralize each other;management