Abstract：ObjectiveTo investigate the mechanism of Huangqi Guizhi Wuwutang （HQGZWWT） in the treatment of diabetic peripheral neuropathy （DPN） in MKR mice via regulating endoplasmic reticulum （ER） stress.MethodThirty-two 8-week-old MKR mice （half were male and half were female） were fed with a high-fat diet for four weeks， and then 1% streptozotocin （STZ） was injected intraperitoneally for five days. After the blood glucose was stabilized， the mice were housed in the cage covered with ice bags for another one hour stimulation per day for four weeks. Mice with fasting blood glucose （FBG） value ≥11.1 mmol·L-1 were randomly divided into model group ， Huangqi Guizhi Wuwutang in original dosage group （30 g·kg-1·d-1）， Huangqi Guizhi Wuwutang in formula dosage group （6.25 g·kg-1·d-1）， and positive drug group （mecobalamin tablets， 0.17 mg·kg-1·d-1）. Another eight MKR mice of the same age were set as blank group and eight FVB mice were normal group. After four weeks of intragastric administration in each group， the change in FBG was tested， and hematoxylin and eosin （HE） staining and transmission electron microscope were used for observing the morphology of sciatic nerve tissue. In addition， the expression of c-Jun N-terminal kinase （JNK）， phosphorylated c-Jun N-terminal kinase （p-JNK） and inositol requiring enzyme 1α （IRE1α） proteins was determined by immunohistochemical test and Western blot （WB）.ResultCompared with the conditions in the normal group and blank group， the time of paw withdrawal， paw licking and tail flick in the model group was shortened （P<0.01）， and the conduction velocity of sciatic nerve was decreased （P<0.01）. Compared with the conditions in the model group， the behavioral and functional indicators were improved by HQGZWWT （P<0.05，P<0.01）. The immunohistochemical test revealed the JNK expression was elevated in the model group compared with the conditions in the normal group and blank group （P<0.05）， while that was lowered by HQGZWWT compared with the condition in the model group （P<0.05）. However， there was no difference among the treatment groups. According to the WB， the expression of IRE1α and p-JNK in the model group was enhanced compared with the conditions in the normal group and blank group （P<0.05，P<0.01）， while that was decreased by HQGZWWT compared with the condition in the model group （P<0.05，P<0.01）. No difference was observed between the HQGZWWTO and HQGZWWTF groups.ConclusionHQGZWWT can improve the neurophysiological function and pathological damage of sciatic nerve， which may be related to its delaying the ER stress response of sciatic nerve.
Abstract：ObjectiveTo investigate the protective effect of Liuwei Dihuangwan on neurovascular injury in SAMP8 mice.MethodThe Alzheimer's disease （AD） model with insufficiency of kidney essence was induced in 75 SAMP8 mice aging 6 months. The model mice were divided into model group， positive control group （donepezil hydrochloride， 0.747 mg·kg-1·d-1）， and high-， medium-， and low-dose Liuwei Dihuangwan groups （2.700， 1.350， 0.675 g·kg-1·d-1）， with 15 mice in each group. Fifteen SAMR1 mice were assigned to a normal control group. All mice were administered continuously for 2 months. The spatial memory of mice was tested by the Morris water maze. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the hippocampus and cortex of brain tissues. The immunohistochemical method （IHC） was used to detect the deposition of amyloid β-protein （Aβ） and the expression of von Willebrand factor （vWF） and CD34 in the hippocampus and cortex of brain tissues. Electron microscopy was used to observe the ultrastructural changes in cerebral microvessels. Western blot was used to detect the protein expression levels of the receptor of advanced glycation endproduct （RAGE）， low-density lipoprotein receptor-related protein 1 （LRP1）， vascular endothelial growth factor A （VEGF-A）， and P-selection in the hippocampus and cortex of brain tissues.ResultCompared with the normal control group， the model group showed prolonged escape latency and swimming distance （P<0.01）， increased number of glial cells， decreased number of nerve cells， blurred tight junctions or enlarged gap of the brain microvascular endothelial cells， severely injured membrane structure， swollen mitochondria of endothelial cells， ruptured membrane， massive dissolution in cristae， increased protein expression of Aβ and vWF in the hippocampus and cortex （P<0.01）， reduced protein expression of CD34 （P<0.05）， elevated protein expression of RAGE and P-selection in the cortex （P<0.01）， and decreased protein expression level of LRP1 and VEGF-A （P<0.01）. Compared with the model group， the Liuwei Dihuangwan groups showed shortened escape latency and swimming distance （P<0.05）， reduced number of glial cells in the cortex and hippocampus， increased number of microvessels in the cortex， clear double-layer membrane structure in tight junctions between the microvascular endothelial cells， increased number of mitochondria with intact membrane and recovered mitochondrial cristae， decreased protein expression of Aβ， vWF， RAGE， and P-selection in the hippocampus and cortex （P<0.05）， and increased protein expression of CD34， LRP1， and VEGF-A （P<0.05）.ConclusionLiuwei Dihuangwan can regulate Aβ metabolism through the RAGE/LRP1 receptor system and promote cerebral microvascular angiogenesis by inhibiting vWF expression and increasing VEGF-A and CD34， thereby improving cerebral microvascular injury in SAMP8 mice.
Keywords：Liuwei Dihuangwan;Alzheimer's disease （AD）;neurovascular unit;receptor of advanced glycation endproduct （RAGE）;low-density lipoprotein receptor-related protein 1 （LRP1）
Abstract：ObjectiveThis study aims to investigate the efficacy and underlying mechanism of Da Chaihutang （DCHT） in treating hepatocellular carcinoma （HCC） in vitro and in vivo.MethodWe employed methyl thiazolyl tetrazolium （MTT） assay and crystal violet staining to observe the proliferation of Hepa1-6 liver cancer cells treated with DCHT at different doses （0， 125， 250， 500， 1 000 mg·L-1） for different time periods （1， 2， 4， 8 days）. The orthotopic liver cancer model was established by injection of 1×106 Hepa1-6 cells into mouse， and then the model mice were randomly assigned into six groups： blank， model， DCHT （0.21， 0.625， 1.875 g·kg-1， ig， qd）， and positive control （5-fluorouracil， 25 mg·kg-1， ip， qod）. After 14 days of administration， the mice were sacrificed， and the liver samples were collected and fixed in 4% paraformaldehyde for hematoxylin-eosin （HE） staining. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Cytoscape 3.7.2， STRING， and DAVID were used for the searching of the key targets of DCHT in treating HCC， the construction of protein-protein interaction （PPI） network， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. Quantitative real-time PCR was performed to determine the mRNA level of interleukin-6 （IL-6） in Hepa1-6 cells and liver tissue. Western blotting was employed to measure the protein levels of the proteins involved in the mitogen-activated protein kinase （MAPK） and signal transducers and activators of transcription 3 （STAT3） signaling pathways.ResultDCHT （500， 1 000 mg·L-1） treatment for 4 and 8 days inhibited the proliferation of Hepa1-6 cells in a dose- and time-dependent manner （P<0.05）. The in vivo assay showed that DCHT （high dose， 1.875 g·kg-1） treatment for 14 days led to high differentiation and unobvious heterogeneity of HCC cells and small necrotic area compared with the model group. Network pharmacology analysis predicted that the potential targets of DCHT in the treatment of HCC were mainly the inflammation cytokines such as IL-6， interleukin-1β （IL-1β）， and tumor necrosis factor-alpha （TNF-α） in HCC microenvironment. The potential signaling pathways involved in the treatment were mainly associated with HCC growth and differentiation， including MAPK and STAT3 signaling pathways. Compared with the blank group， DCHT （1 000 mg·L-1） treatment for 1， 2， 4， and 8 days down-regulated the mRNA level of IL-6 in Hepa1-6 cells （P<0.05）. Similar results were observed in the livers of mice treated with DCHT （0.625， 1.875 g·kg-1）. The in vitro assay demonstrated that DCHT （1 000 mg·L-1） treatment for 4 and 8 days and DCHT （500， 1 000 mg·L-1） treatment inhibited the phosphorylation of extracellular signal-regulated kinases 1/2 （ERK1/2）， c-Jun NH2-terminal kinase/stress-activated protein kinase （JNK）， p38 MAPK， and STAT3 in a dose- and time-dependent manner （P<0.05）. The in vivo assay showed that DCHT （0.625 and 1.875 g·kg-1） treatment only inhibited the phosphorylation of p38 MAPK and STAT3 （P<0.05）.ConclusionThe present study indicates that DCHT can inhibit liver cancer cell proliferation by regulating p38 MAPK/IL-6/STAT3 signaling pathway.
Keywords：hepatocellular carcinoma;Da Chaihutang;p38 mitogen-activated protein kinase （MAPK）;interleukin-6 （IL）-6;signal transducers and activators of transcription 3 （STAT3）
Abstract：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.
Keywords：Banxia Xiexintang;ulcerative colitis;pyroptosis;NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase-1）;inflammation
Abstract：ObjectiveTo observe the regulatory effect of Yuyetang on Ghrelin level in rats with type 2 diabetes mellitus （T2DM）-induced cognitive impairment （DCI） and explore the pathway in the prevention and treatment of DCI.MethodThe T2DM model was induced in rats by intraperitoneal injection of streptozotocin （STZ） combined with the high-fat and high-sugar diet （STZ）. The model rats were divided into model group， metformin group （200 mg·kg-1）， and low-，medium-， and high-dose Yuyetang groups（4.575，9.15， 18.3 g·kg-1）according to the blood glucose， with 10 rats in each group. A normal group was also set up. The rats were administered with corresponding drugs by gavage for 30 days， and the body weight and blood glucose of the rats in each group were observed and recorded. After drug intervention， the learning and memory abilities of rats were tested by the Morris water maze. After the test， the whole brains of rats were sampled for hematoxylin-eosin （HE） staining to observe the pathological changes in the hippocampal CA1 region， and the expression of Ghrelin in gastric tissues and hippocampal CA1 region was detected by immunohistochemistry.ResultCompared with the normal group ， the model group showed increased blood glucose（P<0.01），reduced body weight（P<0.01），prolonged escape latency（P<0.05，P<0.01）， shortened retention time and movement distance in the target area，decreased number of platform crossings（P<0.01）， abnormal morphology and structure of cells with disordered arrangement and reduced number in the hippocampal CA1 region， and decreased expression of Ghrelin in the serum，hippocampal CA1 region， and gastric tissues（P<0.05， P<0.01）. Compared with the model group， the medium- and high-dose Yuyetang groups showed increased body weight， while all Yuyetang groups showed reduced blood glucose（P<0.01）， shortened escape latency （P<0.05）， prolonged retention time and movement distance in the target area，increased platform crossings （P<0.05， P<0.01）， improved morphology and structure of cells， increased number of normal cell in the hippocampal CA1 region， and elevated Ghrelin levels in the serum， gastric tissues， and hippocampal CA1 region（P<0.05， P<0.01）.ConclusionYuyetang can effectively improve the cognitive ability of DCI rats， and its mechanism may be related to the regulation of Ghrelin levels in the serum， hippocampal CA1 region， and gastric tissues.
Keywords：type 2 diabetes mellitus-induced cognitive impairment （DCI）;Yuyetang;Ghrelin;treatment based on spleen and stomach;diagnostic standard
Abstract：ObjectiveTo investigate the effect of Chuanshanlong granule on Toll-like receptor 4 （TLR4）/myeloid differentiation protein 88 （MyD88）/nuclear transcription factor -κB （NF-κB） signaling pathway， and to explore the mechanism of its treatment of autoimmune thyroiditis （AIT） in rats.MethodForty AIT models were established following excess iodine and injection of porcine thyroglobulin and Freund's adjuvant into Lewis rats for six weeks. Then the rats were randomly divided into the model group， Chuanshanlong granule low-， medium- and high-dose group （0.52， 1.03， 2.06 g·kg-1·d-1）， with ten in each group. Rats in the Chuanshanlong granule low-， medium- and high-dose groups were separately given 0.01 mL·g-1·d-1 Chuanshanlong granule， and those in the normal group and the model group were given the same volume of deionized water for eight weeks. Serum of rats was taken to measure thyroglobulin antibody （TgAb） and thyroid peroxidase antibody （TPOAb） by enzyme-linked immunosorbent assay （ELISA）， and the concentrations of free triiodothyronine （FT3）， free thyroxine （FT4） and thyroid stimulating hormone （TSH） were detected. The rat thyroid lobes were stained with hematoxylin and eosin （HE）， and the pathological changes were observed under light microscope. In addition， the relative expression of TLR4， MyD88， NF-κB protein and mRNA was determined by immunohistochemistry and real-time polymerase chain reaction （Real-time PCR）.ResultCompared with the conditions in the normal group， the serum concentrations of TPOAb and TgAb （P<0.01） and FT3 and FT4 （P<0.01） increased and TSH decreased （P<0.01） in the model group. Compared with the conditions in the model group， the concentrations of TPOAb and TgAb in the Chuanshanlong granule treatment groups reduced （P<0.01）， and the concentrations of FT3 and FT4 were lowered （P<0.01） while TSH increased （P<0.01） in the Chuanshanlong granule high-dose group. HE staining showed that there was lymphocyte infiltration in the thyroid follicular space， a large number of destroyed or diminished follicular cavities， decreased colloid content， and thinned or destroyed follicular wall in the model group， while the thyroid lymphocyte infiltration in the Chuanshanlong granule treatment groups was significantly less and the structure of thyroid follicles was more complete than those in the model group. Compared with the normal group， the model group had up-regulated relative expression of TLR4， MyD88 and NF-κB protein （P<0.01） and mRNA （P<0.01）. Compared with the model group， the Chuanshanlong granule high-dose group had down-regulated relative expression of TLR4 protein and mRNA （P<0.05）， MyD88 protein （P<0.01） and mRNA （P<0.05）， and NF-κB protein and mRNA （P<0.01）.ConclusionChuanshanlong granule may play a therapeutic role in AIT by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.
Abstract：ObjectiveTo investigate the inhibitory effect of hederasaponin B on gastric cancer HGC-27 cell and the mechanism.MethodMethyl thiazolyl tetrazolium （MTT） assay， hematoxylin-eosin （HE） staining， 4'，6-diamidino-2-phenylindote （DAPI） staining， colony formation assay， scratch assay， and flow cytometry were employed for the analysis of apoptosis and cell cycle. Thereby， the inhibitory effect of hederasaponin B on gastric cancer HGC-27 cell was investigated. Then the Pharm Mapper， UniProt， Swissdock， STRING， and Metascape were used for target screening， gene annotation， molecular docking， protein-protein interaction （PPI） network construction， Gene Ontology （GO） term and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis to explore the mechanism.ResultHederasaponin B （15， 30， 60， 120 μmol·L-1） can significantly reduce the survival rate of HGC-27 cell （P<0.01） in a time-dependent and dose-dependent manner compared with the blank group. It had no significant toxicity to normal GES-1 cell at concentration below 120 μmol·L-1. Compared with the blank group， hederasaponin B （30， 60， 120 μmol·L-1） induced cytoplasmic vacuolization， and nuclear deformation and karyopyknosis， inhibited the migration of HGC-27 cell （P<0.01）， and brought about the apoptosis （P<0.05， P<0.01） and cell cycle arrest of HGC-27 cell （P<0.05， P<0.01）. Hederasaponin B （10， 20， 30 μmol·L-1） also suppressed the independent survival ability and proliferation ability of HGC-27 cell （P<0.01）. The possible action targets were kinesin-like protein KIF11， cGMP-specific 3，5 cyclic phosphodiesterase， caspase-3， serine/threonine protein kinase Chk1， proto-oncogene tyrosine protein kinase， epidermal growth factor receptor， and mitogen-activated protein kinase （MAPK） 8. The mechanism may be related to MAPK signaling pathway （pathways in cancer）， adhesion connection， focal adhesion and proteoglycans in cancer （epithelial cell signaling pathways in Helicobacter pylori infection）.ConclusionHederasaponin B exerts significant inhibitory effect on gastric cancer HGC-27 cell through multiple targets and multiple pathways.
Keywords：hederasaponin B;gastric cancer HGC-27 cell;inhibitory effect;bioinformatics;mechanism
Abstract：ObjectiveTo investigate the effect of modified Taohe Chengqitang on NOD-like receptor protein 3 （NLRP3） inflammasome activation in rats with diabetic cardiomyopathy.MethodSPF male SD rats aged 3-4 weeks were randomly divided into a normal group and an experimental group. The rats in the experimental group were fed on a high-fat diet for 4 weeks and then received intraperitoneal injection of streptozotocin （STZ） at 35 mg·kg-1 to induce the diabetes model. The rats in the experimental group were randomly divided into model group， low- and high-dose modified Taohe Chengqitang groups （11.7 g·kg-1 and 23.4 g·kg-1）， and metformin hydrochloride group （67.5 mg·kg-1） according to the fast blood glucose （FBG）. The cardiac function and structure of rats were detected by ultrasonic imaging after 8 weeks of continuous intragastric administration. Blood samples from the femoral artery were collected to detect FBG， triglyceride （TC）， and total cholesterol （TG） of rats. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in rat myocardium. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease 1 （Caspase-1）， and phosphorylated nuclear factor kappa-B p65 （p-NF-κB p65） in the myocardium was detected by Western blot.ResultCompared with the normal group， the model group showed increased levels of FBG， TC， and TG （P<0.01）， decreased left ventricular ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.05）， myocardial hypertrophy and myocardial fibrosis as revealed by HE staining， increased serum levels of 1L-1β and 1L-18 and protein expression of NLRP3， ASC， Caspase-1， and p-NF-κB p65 in myocardial tissues （P<0.01）. Compared with the model group， the modified Taohe Chengqitang groups and the metformin group showed reduced levels of FBG， TC， and TG （P<0.05）， restored EF and FS （P<0.05）， improved pathological changes in myocardial tissues， and decreased serum levels of IL-1β and IL-18 and protein expression of NLRP3， ASC， Caspase-1， and p-NF-κB p65 in myocardial tissues （P<0.05）. The improvement was more significant in the high-dose modified Taohe Chengqitang group （P<0.05）.ConclusionModified Taohe Chengqitang can protect the myocardium by inhibiting the activation of NLRP3 inflammasomes.
Abstract：ObjectiveTo explore the mechanism of Broussonetiae Fructus （BF） in preventing and treating drug-induced liver injury （DILI） induced by acetaminophen （APAP） through the endoplasmic reticulum stress pathway.MethodSixty C57BL/6N mice were randomly divided into normal group， model group， silybin group （3.4 g·kg-1）， and high-， medium- and low-dose BF groups （3.0， 1.5， 0.75 g·kg-1）， with 10 mice in each group. The DILI model was induced by intragastric administration of APAP at 800 mg·kg-1， and drugs were administered simultaneously for 10 consecutive days. The serum contents or activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， and direct bilirubin （DBIL） were measured. Hematoxylin-eosin（HE） staining was performed to observe the pathological changes in liver tissues. The morphological changes in liver mitochondria were observed by transmission electron microscopy. The activities or content of superoxide dismutase （SOD）， malondialdehyde （MDA）， total antioxidant capacity （T-AOC）， glutathione （GSH）， glutathione disulfide （GSSG）， glutathione peroxidase （GSH-Px）， and adenosine triphosphate （ATP） in the serum and liver tissues were detected by the colorimetric method. The expression of reactive oxygen species （ROS） in liver tissues was detected by immunofluorescence. The gene expression of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and c-Jun N-terminal kinase （JNK） in liver tissues was detected by Real-time quantitative polymerase chain reaction （PCR）.ResultCompared with the normal group， the model group showed increased serum activities or content of ALT， AST， TBIL， and DBIL （P<0.01）， increased MDA and GSSG contents （P<0.01）， decreased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.01）， swollen hepatocytes with inflammatory infiltration and lamellar necrosis， swollen and broken mitochondria of hepatocytes， and increased mRNA expression of GRP78， CHOP， and JNK （P<0.01）. Compared with the model group， the groups with drug intervention showed decreased serum content or activities of ALT， AST， TBIL， and DBIL （P<0.05， P<0.01）， reduced MDA and GSSG contents（P<0.05， P<0.01）， and increased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.05， P<0.01）， improved swollen hepatocytes， inflammatory infiltration， and lamellar necrosis， recovered bilayer membrane structure in mitochondria of hepatocytes， and decreased mRNA expression of GRP78， CHOP， and JNK （P<0.05， P<0.01）.ConclusionBF has preventive and therapeutic effects on APAP-induced DILI mice， and the mechanism may be related to the reduction of endoplasmic reticulum stress and oxidative stress level in vivo.
Abstract：ObjectiveTo explore the mechanism of cucurbitacin B （CuB） in inhibiting cell proliferation and glycolysis.MethodCell counting kit-8 （CCK-8） was applied to investigate the effect of different concentrations of CuB （0， 40， 80， 120， 160， 200， 400， and 800 nmol·L-1） on the proliferation of HuCCT1 cells. The effect of different concentrations of CuB （50， 100， and 200 nmol·L-1） on the colony formation ability of HuCCT1 cells was detected by plate cloning assay. The effect of different concentrations of CuB （50， 100， 200 nmol·L-1） on the HuCCT1 cell cycle was analyzed by flow cytometry. Visible spectrophotometry was employed to detect the activity of key glycolytic enzymes hexokinase （HK） and pyruvate kinase （PK）） and changes in glucose consumption， lactate production， and adenosine triphosphate （ATP） production in HuCCT1 cells after administration of different concentrations of CuB （50， 100， 200 nmol·L-1）. Western blotting was used to assay the effect of CuB on the expression of cell cycle-related proteins， proliferation-related proteins， key glycolytic proteins， and Akt/mammalian target of rapamycin （mTOR） pathway-related proteins.ResultAs compared with the blank group， CuB at dose of 160-800 nmol·L-1 after 24 h administration and CuB at dose of 80-800 nmol·L-1 after 48 h administration inhibited the proliferation of HuCCT1 cells in a time- and dose-dependent manner （P<0.05， P<0.01）， and the median inhibitory concentration was 200 nmol·L-1 48 h after administration. CuB can restrain the colony formation ability of HuCCT1 cells in a dose-dependent manner （P<0.01）， and block HuCCT1 cell cycle in G2 phase （P<0.05， P<0.01）. CuB （100 and 200 nmol·L-1） can suppress the activities of HK and PK and reduce cell glucose consumption and production of lactate and ATP （P<0.05， P<0.01）. Western blot results showed that CuB （100 and 200 nmol·L-1） can inhibit the protein levels of cycle-related protein Cyclin B1， proliferating cell nuclear antigen （PCNA）， HK1， HK2， PKM1， PKM2， phosphorylated Akt （p-Akt）， phosphorylated mTOR （p-mTOR）， and phosphorylated ribosomal protein S6 （p-RPS6） （P<0.05， P<0.01）.ConclusionCuB can inhibit aerobic glycolysis in HuCCT1 cells via the Akt/mTOR pathway， thereby affecting cell proliferation.
Keywords：cucurbitacin B;intrahepatic cholangiocarcinoma;Akt/mammalian target of rapamycin （mTOR） pathway;glycolysis;HuCCT1 cell proliferation
Abstract：ObjectiveTo observe the intervention effect of Ruyi Zhenbao pills （RYZBP） on central pain after thalamic stroke in mice and explore the underlying mechanism.MethodThe central post-stroke pain syndrome （CPSP） model was induced by stereotactic injection of type Ⅳ collagenase into the hypothalamus in mice. The mice were divided into a sham group， a model group， low-， medium-， and high-dose RYZBP groups （0.65， 1.3， 2.6 g·kg-1）， and a pregabalin group （0.075 g·kg-1）. Seven days after modeling， the mice in the groups with drug intervention were administered with corresponding drugs by gavage according to the body mass， once per day for 25 days， while those in the sham group and the model group received an equal volume of normal saline. During this period， mechanical pain and cold pain were detected at different time points， and the apoptotic state of brain tissue cells was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. The 36 classical broad-spectrum inflammatory factors were quantitatively analyzed by liquid-phase chip technology， and differential molecules were screened out and verified by Western blot and enzyme-linked immunosorbent assay （ELISA）.ResultCompared with sham operation group, mechanical pain threshold and cold sensitive pain threshold in model group were significantly changed （P<0.01）. TUNEL results showed that apoptosis of brain cells was obvious. Western blot and ELISA results showed that the expressions of interleukin-1α (IL-1α) and chemokine ligand 5 (CCL5) increased in hypothalamus tissue and serum， while the expressions of Ang-2, granulocyte-colony-stimulating factor (G-CSF) and IL-4 decreased significantly （P<0.01）. Compared with model group， RYZBW dose groups significantly increased mechanical pain threshold， decreased cold sensitivity pain threshold， decreased hypothalamus cell apoptosis ratio （P<0.01）， decreased the expression of IL-1α and CCL5 in hypothalamus tissue and serum， while the expression of ANG-2， G-CSF and IL-4 were significantly increased （P<0.05）.ConclusionRYZBP can relieve hyperalgesia in CPSP mice， and its mechanism is related to the regulation of the expression of pro-/anti-inflammatory factors IL-1α， CCL5， IL-4， G-CSF， and Ang-2.
Keywords：Ruyi Zhenbao pills;central pain after thalamic stroke;type Ⅳ collagenase;inflammatory factor
Abstract：ObjectiveTo explore the effect and mechanism of Zuogui Jiangtang Tongmai prescription （ZGJTTMP） on astrocytes （ASs） injured by advanced glycation end products（AGEs） combined with oxygen-glucose deprivation （OGD）.MethodCell counting kit-8 （CCK-8） was used to determine the optimal concentration of AGEs and the action time of OGD， and the optimal blood concentration of ZGJTTMP was selected for follow-up experiments. ASs were divided into normal group， model group （AGEs + OGD）， ZGJTTMP group， an adenosine 5'-monophosphate-activated protein kinase （AMPK） inhibitor （Compound C） group， AMPK activator （AICAR） group， and combination group （ZGJTTMP + AICAR）. The morphological changes in ASs in each group were observed under an inverted microscope. The cell survival rate in each group was detected by CCK-8. The content of interleukin-1β（IL-1β）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） was detected by enzyme-linked immunosorbent assay （ELISA）. The number of autophagosomes in each group was counted under an electron microscope. The expression of microtubule-associated protein light chain 3 （LC3） was observed by immunofluorescence. The protein expression of LC3， p62， p-AMPK， AMPK， p-mammalian target of rapamycin （mTOR）， mTOR， p-UNC-51 like kinase 1 （ULK1）， and ULK1 was detected by Western blot.ResultAccording to the results of cell survival rate， 200 mg·L-1 AGEs and OGD for 6 h were selected as the optimal modeling conditions for the model group， and 5% was selected as the optimal blood concentration of ZGJTTMP. Under the inverted microscope， the cells were severely damaged after modeling， but the cell injury in the ZGJTTMP group and the Compound C group was significantly improved. As revealed by ELISA results， the content of IL-1β， IL-6， and TNF-α in the model group increased （P<0.01）， and the content of inflammatory factors in the ZGJTTMP group and the Compound C group decreased （P<0.01）. Under the electron microscope， the number of autophagosomes in the model group increased significantly. The immunofluorescence results showed that the expression area of LC3 increased in the model group （P<0.01）， and the ZGJTTMP group and the Compound C group showed decreased number of autophagosomes and reduced expression area of LC3 （P<0.01）. As demonstrated by the results of Western blot， compared with the normal group， the model group showed increased expression of LC3Ⅱ/LC3Ⅰ and p-AMPK/AMPK （P<0.01） and decreased p62， p-mTOR/mTOR， and p-ULK1/ULK1 （P<0.01）. Compared with the model group， the ZGJTTMP group and the Compound C group showed decreased expression of LC3Ⅱ/LC3Ⅰ and p-AMPK/AMPK （P<0.01） and increased p62， p-mTOR/mTOR， and p-ULK1/ULK1 （P<0.01）.ConclusionZGJTTMP possesses a protective effect on ASs with inflammatory injury by AGEs combined with OGD， which may be achieved by inhibiting the activation of the AMPK/mTOR/ULK1 pathway related to autophagy， thus inhibiting the overexpression of autophagy.
Keywords：astrocytes;autophagy;Zuogui Jiangtang Tongmai prescription;adenosine 5′-monophosphate-activated protein kinase （AMPK）;mammalian target of rapamycin （mTOR）;UNC-51 like kinase 1 （ULK1）
Abstract：ObjectiveTo explore the effect of Yifei Huatan decoction on relieving airway hyperviscosity in asthmatic rats with spleen deficiency syndrome and its mechanism.MethodFifty-five SPF level SD rats at 8-9 week of age were used to induce asthma with spleen deficiency syndrome by animal modeling of traditional Chinese medicine combined with asthma of western medicine. After successful modeling， the rats were divided into model group， dexamethasone group， low， medium， and high-dose Yifei Huatan decoction groups by random number table method， and 11 clean SD rats at 8-9 week of age were recorded as a normal group. Rats in the dexamethasone group were given 0.087 5 mg kg-1 dexamethasone acetate by gavage. Rats in the low， medium， and high-dose Yifei Huatan decoction groups were given 0.8， 1.6， 3.2 g kg-1 Yifei Huatan decoction liquid extract by gavage， respectively. Rats in the model group and the normal group were given 10 mL kg-1 distilled water. The medicine were given once per day for 8 w， and the general situation of each group was observed. The levels of interleukin-4 （IL-4）， IL-13， and interferon-γ （IFN-γ） in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）. The pathological changes in lung tissues of rats were observed by hematoxylin-eosin （HE） staining. Alcian blue-periodic acid Schiff （AB-PAS） staining was used to detect the hyperplasia of airway goblet cells and mucus secretion in rats. The mRNA expressions of transforming growth factor-β1 （TGF-β1）， Smad2， Smad3， mucin 5AC （MUC5AC）， and mucin 5B （MUC5B） in the lung tissues of rats were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expressions of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B in the lung tissues of rats were detected by Western blot.ResultAs compared with the normal group， rats in the model group showed the symptoms of spleen deficiency syndrome， such as decreased body weight， muscle emaciation， decreased food intake， increased water intake， increased anal temperature， tiredness， and decreased swimming endurance， accompanied by dyspnea symptoms such as wheezing and nodding. As compared with the normal group， IL-4 and IL-13 levels in the BALF of the model group were significantly increased （P<0.01）， while the IFN-γ level was significantly decreased （P<0.01）. In the model group， a large number of inflammatory cells were observed in the mucosa and submucosa of the airway， and the smooth muscle of the trachea was significantly thickened. The hyperplasia， deformation， and exfoliation of various epithelial cells were observed in the mucosa， and the pathological scores of lung tissue increased significantly （P<0.01） in the model group. A large number of goblet cells were observed in the airway with the formation of plenty of mucous thrombus in the model group， and the positive relative staining area of airway， and mRNA and protein expressions of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B were significantly increased （P<0.01）. As compared with the model group， IL-4 and IL-13 levels in BALF of the dexamethasone group and the Yifei Huatan decoction groups decreased， while the IFN-γ level increased. The inflammatory cell infiltration in airway mucosa and submucosa， the thickening of tracheal smooth muscle， the hyperplasia， deformation， and exfoliation of epithelial cells in mucosa were gradually decreased， and the pathological scores of lung tissues decreased significantly （P<0.01） in the dexamethasone group and the Yifei Huatan decoction groups. Goblet cell proliferation gradually decreased， and the positive relative staining area of airway， and mRNA and protein relative expressions of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B decreased with statistically significant difference （P<0.05， P<0.01）. There was no significant difference in the above indexes in the dexamethasone group and the Yifei Huatan decoction low-dose group. The above indexes were dose-dependent in the low， medium， and high-dose Yifei Huatan decoction groups.ConclusionYifei Huatan decoction reduces airway hyperviscosity in asthmatic rats with spleen deficiency syndrome， which may be related to the inhibition of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B expressions， down-regulation of IL-4 and IL-13 levels， and up-regulation of IFN-γ level.
Abstract：ObjectiveTo analyze factors related to the suspected allergic reaction of elememe emulsion injection based on hospital information system.MethodData on cases that used elememe emulsion injection were collected from the information systems of 60 first-class hospitals nationwide. The nested case-control design method was adopted. Finally， 30 cases were included in the suspected allergy group and 120 cases in the control group. SAS 9.3 was employed for descriptive analysis of the gender， age， occupation， admission route， conditions of patients at the admission， and the diagnosis with frequency and percentage. The factors affecting the occurrence of suspected allergic reaction were analyzed by conventional logistic regression and propensity score weighted logistic regression. In the case that the number of independent variables was larger than the sample number， MCP （minimax concave penalty） was used to screen the key variables and the conditions of patients at admission， conditions of patients during hospitalization， hospital stay， diagnostic information， and medication information were compared between two groups.ResultThe male-to-female ratio was about 2∶1 in both groups and most of the patients were 46-65 years old. Patients in the control group were mainly "professional and technical personnel"， and the majority in the suspected allergy group were "business and service personnel" and "clerks and related personnel". They were mainly admitted at the outpatient and conditions of patients were average at the admission. Compared with the control group， suspected allergy group showed severe conditions during the hospitalization， short average hospital stay， large proportion with intravenous infusion， and low cure rate and effective rate. The results of logistic regression analysis showed no statistical difference in conditions of patients at admission， hospital stay， combined diseases， medicine dosage， and treatment course.ConclusionThe suspected allergic reaction of elememe emulsion injection mainly occurs in the first administration with rapid onset even with the dose lower than the commonly used one. The occurrence is related to the intravenous infusion and the severe conditions of patients during hospitalization and has nothing to do with the conditions of patients at admission， hospital stay， treatment course， use of other medicines， and diagnostic information. In summary， it is mainly related to the constitution and immune status of patients.
Abstract：ObjectiveTo evaluate the efficacy of Zishui Bugan decoction on perimenopausal insomnia of liver-kidney deficiency type and the safety.MethodA randomized， double-blind， placebo-controlled trial was designed. To be specific， 72 patients of perimenopausal insomnia with Liver-kidney deficiency were randomized into the treatment group and the control group at the ratio of 1∶1 and they were respectively treated with Zishui Bugan decoction and placebo for 3 weeks. The Pittsburgh sleep quality index （PSQI）， modified Kupperman index， traditional Chinese medicine （TCM） syndrome score， self-rating anxiety scale （SAS） score， and self-rating depression scale （SDS） score， were compared before and after treatment to determine the clinical efficacy， with adverse effects recorded.ResultThe total effective rate for insomnia was 85.3%（29/34） in treatment group and 17.6%（6/34） in control group（Z=-5.582，P<0.01）. After treatment， PSQI score， modified Kupperman index， TCM syndrome score， and SAS score were improved in both groups （P<0.05， P<0.01）， particularly the treatment group which showed significant difference from the control group （P<0.05，P<0.01）. The safety indicators were insignificantly different between two groups before and after treatment. No related adverse effects were reported in both groups during the treatment.ConclusionZishui Bugan decoction can improve the sleep quality and alleviate the menopausal symptoms， such as depression and anxiety， which shows ideal efficacy and safety for the perimenopausal insomnia with liver-kidney deficiency type.
Abstract：ObjectiveTo observe the clinical effect of Xijiao Dihuangtang combined with acupuncture on the treatment of systemic lupus erythematosus （SLE） with syndrome of intense heat toxin.MethodA total of 102 cases of SLE with syndrome of intense heat toxin （admitted from January 2020 to December 2021） were divided into a control group and an observation group by random number table method， with 51 cases in each group. Patients in the control group received conventional western medicine treatment （hydroxychloroquine sulfate + poonisone acetate tablets）. Patients in the observation group were given Xijiao Dihuangtang combined with acupuncture based on the treatment of the control group. Clinical efficacy， onset time， symptom improvement time， skin lesion regression time， and hospital stays were recorded. Blood routine index change， 24 h urine protein levels， double-stranded DNA （ds-DNA） antibodies resistance index changes， traditional Chinese medicine （TCM） syndrome integral changes， and changes in serum cytokine indexes， blood rheology indexes， and T lymphocyte subsets indexes were observed. SLE changes in disease activity index （SLEDAI-2000）， quality of life （SF-36） scores， and adverse reactions were explored.ResultThe total effective rate was 96.08% （49/51） in the observation group， higher than 84.31% （43/51） in the control group （χ2=3.991， P<0.05）. The onset time， symptom improvement time， skin lesion regression time， and hospital stays in the observation group were shorter than those in the control group （P<0.05，P<0.01）. Before treatment， erythrocyte sedimentation rate （ESR）， platelet count （PLT）， hemoglobin （HGB）， white blood cell count （WBC）， and other blood routine indexes， 24h urinary protein levels， anti-ds-DNA， TCM syndrome integral core， serum cytokine indexes including interleukin-4 （IL-4）， IL-6， soluble interleukin-2 receptor （sIL-2R）， blood rheology indexes （fibrinogen， plasma viscosity， and whole blood viscosity），T lymphocyte subsets indexes （CD4+， CD8+， and CD4+/CD8+）， SLEDAI-2000， and SF-36 score comparison in both groups had no statistical significance. After treatment， the above indicators were improved in each group （P<0.05）， and the indicators in the observation group was better than that in the control group （P<0.05）. In terms of the adverse reactions， there was 1 case of digestive tract reaction， 1 case of elevated aminotransferase， and 1 case of insomnia in the observation group. There were 2 cases of digestive tract reaction，1 case of infection， and 1 case of elevated transaminase in the control group. The difference of the adverse reactions between the two groups had no statistical significance.ConclusionXijiao Dihuangtang combined with acupuncture has good clinical effect on the treatment of SLE with syndrome of intense heat toxin， and the method is safe， reliable， and worthy of application.
Keywords：systemic lupus erythematosus;syndrome of intense heat toxin;Xijiao Dihuangtang;acupuncture;curative effect;adverse reactions
Abstract：ObjectiveTo observe the difference in the efficacy of three kinds of traditional Chinese medicine （TCM） injections on rat model of heart failure induced by transverse aortic constriction （TAC）， explore the TCM syndrome of the model based on the theory of correspondence of prescription and syndrome， and reveal the biological basis of prescription-syndrome from the perspective of metabolism.MethodRats were treated with TAC for modeling and were divided into Shenmai injection group （6.0 mL·kg-1）， model group， Danhong injection group （6.0 mL·kg-1）， Shenfu injection group （6.0 mL·kg-1） and trimetazidine group （10 mg·kg-1）， and sham operation group was set up as control. After drug intervention for 15 days， echocardiography， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and myocardial histopathological staining were performed for each group， so as to compare the efficacy to select the effective injection. Colorimetry was used to detect the serum glucolipid metabolism after the intervention of the effective injection， and ultra high performance liquid chromatography-mass spectrometry was used to observe the metabolites and related metabolic pathways in myocardial tissue.ResultCompared with the sham operation group， the left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （FS） in the model group decreased （P<0.01）， while the left ventricular end-diastolic diameter （LVIDd）， left ventricular internal diameter at end-systole （LVIDs） and NT-proBNP level increased （P<0.01）. Compared with model group， LVEF and FS increased （P<0.01）， LVIDd， LVIDs and NT-proBNP level decreased （P<0.05， P<0.01） in Danhong injection group， NT-proBNP level in Shenfu injection group decreased （P<0.05）， LVIDd and NT-proBNP level increased （P<0.05， P<0.01） in Shenmai injection group， in trimetazidine group， LVEF and FS increased （P<0.01）， while LVIDs and NT-proBNP level decreased （P<0.05， P<0.01）. Serum glucose， low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels in Danhong injection group and trimetazidine group were adjusted by callbacks （P<0.01， P<0.05）. There were the callback of 9 myocardial metabolites in Danhong injection group， including glycine， serine and threonine metabolism， glyoxylate and dicarboxylate metabolism， glycerol phospholipid metabolism. There were the callback of 10 myocardial metabolites in trimetazidine group， including glycerol phospholipid metabolism.ConclusionThe efficacy of Danhong injection on heart failure model induced by TAC is significant and superior to Shenfu injection and Shenmai injection， suggesting that the model is closely related to heart-blood stasis. The biological mechanism of Danhong injection interfering with the model involves regulating the metabolic disorder of lipid， glucose， amino acid and butyric acid.
Keywords：transverse aortic constriction （TAC）;heart failure （HF）;correspondence of prescription and syndrome;metabolomics;biomarkers;ultra high performance liquid chromatography-mass spectrometry （UPLC-MS/MS）;amino acids
Abstract：ObjectiveTo study the changes of microbiota in different intestinal niches in the instance of diarrhea with intestinal dampness-heat syndrome and cold-dampness disturbing spleen syndrome， so as to provide objective evidence for treating diarrhea with different methods from the perspective of intestinal flora.MethodThe 16S rRNA gene high-throughput sequencing data of model mice with diarrhea of the two syndromes and the model mice after prescription intervention were retrieved from National Center for Biotechnology Information （NCBI）， and the intestinal dominant bacteria and microbial functions were compared among groups. Spearman's correlation coefficient among the microorganisms in each group was calculated and the co-occurrence networks of intestinal microbiota were constructed to study the interaction of the microbiota.ResultThe microbiota imbalance in intestinal contents of mice with diarrhea of intestinal dampness-heat syndrome was characterized by the enrichment of Muribaculum and Aerococcus， while the imbalance in intestinal mucosa was manifested by the enrichment of Gram-negative Neisseria， Capnocytophaga， and Prevotella （P<0.05）. However， after the treatment with Gegen Qinliantang， the microbiota in two distinct ecosystems was characterized by the enrichment of Lactobacillus and the abundance of Streptococcus in intestinal mucosa was increased. The microbiota imbalance in intestinal contents of diarrhea with cold-dampness disturbing spleen syndrome was characterized by the enrichment of Lactobacillus （P<0.01） and Clostridium sensu stricto 1， while the intestinal mucosa was dominated by the increase of Candidatus arthromitus and Enterobacter. However， after the treatment with Huoxiang Zhengqi powder， the intestinal contents were characterized by Lactobacillus enrichment， while the intestinal mucosal flora was featured by the enrichment of C. arthromitus， Pseudomonas， and Bacillus. Overall， the contribution of dominant bacteria in intestinal mucosa to the difference was higher than that in intestinal contents， and more dominant bacteria in the intestinal mucosa interacted with other bacteria.ConclusionMicrobiota imbalance is different for diarrhea of different syndromes， and the therapeutic effects of corresponding prescriptions are also different. In addition， the microbiota imbalance has different characteristics between intestinal niches for mice with diarrhea of the same syndrome. Therefore， intestinal flora may be one of the biological bases for exploring the characteristics of "treating the diarrhea with different methods" in Chinese medicine.
Keywords：diarrhea;intestinal dampness-heat syndrome;cold-dampness disturbing spleen syndrome;treating the same disease with different methods;Chinese medicine
Abstract：ObjectiveTo investigate the effects of inoculation of potassium-solubilizing bacteria on the physiological characteristics of Paris polyphylla var. yunnanensis.MethodThe effects of different potassium-solubilizing bacteria on leaf area，photosynthetic pigment content， and active component indexes of P. polyphylla var. yunnanensis were investigated by pot planting at room temperature.ResultThe results showed that the inoculation of potassium-solubilizing bacteria could increase the leaf area of P. polyphylla var. yunnanensis. The largest average leaf area was observed in the S3 group，reaching 10.497 cm2，with a maximum increase of 11.0% compared with that of the CK group. The inoculation of potassium-solubilizing bacteria could increase the content of photosynthetic pigments in leaves. Among them，the increase in chlorophyll a content was significant （P<0.05），which was 80.6% higher than that of the CK group. The chlorophyll a/b values in all treatment groups were higher than that of the CK group. The activities of superoxide dismutase（SOD），catalase（CAT） and peroxidase（POD） in the leaves of P. polyphylla var. yunnanensis increased by 88.4%，33.8%， and 30.6%，respectively， as compared with that in the CK group. The inoculation of potassium-solubilizing bacteria could promote the accumulation of osmoregulation substances such as soluble sugar and soluble protein in leaf cells of P. polyphylla var. yunnanensis，with a maximum increase of 55.3% and 70.5% respectively compared with that of the CK group. Meanwhile，it also reduced the content of malondialdehyde（MDA），with a maximum decrease of 34.1% compared with that of the CK group. The results of correlation analysis showed that there were some correlations between different chemical components in P. polyphylla var. yunnanensis leaves.ConclusionThe inoculation of potassium-solubilizing bacteria can effectively promote the growth and development of P. polyphylla var. yunnanensis and improve its survival ability in adversity. It is of practical scientific significance and potential application value for improving the survival rate of P. polyphylla var. yunnanensis by artificial planting.
Keywords：Paris polyphylla var. yunnanensis;potassium-solubilizing bacteria;physiology and biochemistry;active components
Abstract：ObjectiveThe effect of inoculation with different organophosphate-resolving bacteria or compound bacteria on the quality of Paris polyphylla var. yunnanensis medicinal materials and rhizosphere soil fertility were studied to provide a reference for the development and application of biological bacterial fertilizer in artificial cultivation of P. polyphylla var. yunnanensis.MethodThe three dominant species of organophosphate-solubilizing bacteria were inoculated separately and in combination in sterilized soil by single-factor indoor pot planting， and no inoculation was used as the control group. The effect of inoculation of organophosphate-solubilizing bacteria on total saponins content in rhizomes of P. polyphylla var. yunnanensis， as well as microbial numbers， enzyme activities and nutrient contents in rhizosphere soil were analyzed.ResultIn the seven treatments inoculated with organophosphate-solubilizing bacteria， the total saponin content in the rhizomes of Paris polyphylla var. yunnanensis was increased by 16.42%， 3.83%， 16.86%， 33.69%， 2.11%， 13.44%， and 28.83%， respectively， compared with the control. Inoculation with organophosphate-solubilizing bacteria increased the number of soil microorganisms to varying degrees， and the effects of S6 and S7 treatments were the most significant. Inoculation with organophosphate-solubilizing bacteria improved the enzyme activity， and the effect of S7 treatment was the most significant. The activities of acid phosphatase， neutral phosphatase， alkaline phosphatase， protease， invertase and catalase were 49.96% and 104.67% ， 110.17%， 99.61%， 26.26%， 11.29% higher than those of the control， respectively. Inoculation with organophosphate-solubilizing bacteria reduced the pH of the rhizosphere soil and increased the content of soil available nutrients. Under the S7 treatment， the contents of alkaline hydrolyzable nitrogen， available phosphorus and available potassium in the rhizosphere soil of P. polyphylla var. yunnanensis were 181.46%， 51.64% and 42.62% higher than those of the control， respectively. Correlation analysis showed that there was a significant positive correlation between total saponins and phosphatase activities， a significant positive correlation between soil microorganisms and soil enzyme activities， and a very significant positive correlation between soil nutrients.ConclusionInoculation of different organophosphate-resolving bacteria or compound bacteria can improve the quality and rhizosphere soil fertility of P. polyphylla var. yunnanensis. Among them， the mixed inoculation of three kinds of bacteria and the mixed inoculation of B. mycoides and B. wiedmannii have the best effect.
Keywords：Paris polyphylla var. yunnanensis;organophosphate-solubilizing bacteria;total saponins;microbial count;enzymatic activity;nutrient content
Abstract：ObjectiveTo study the effect of organophosphate-solubilizing bacteria and compound bacteria on the photosynthesis and physiological and biochemical characteristics of leaves of Paris polyphylla var. yunnanensis， and to provide a reference for selecting suitable bacterial fertilizers in artificial cultivation of this medicinal species.MethodPot experiment was carried out indoor and the following groups were designed： control （CK）， inoculation with Bacillus mycoides （S1）， inoculation with B. wiedmannii （S2）， inoculation with B. proteolyticus （S3）， inoculation with B. mycoides and B. wiedmannii （S4）， inoculation with B. mycoides and B. proteolyticus （S5）， inoculation with B. wiedmannii and B. proteolyticus （S6）， and inoculation with B. mycoides， B. wiedmannii and B. proteolyticus （S7）. Then， the growth and development， photosynthesis， and various physiological and biochemical indexes of the leaves of this species were observed.ResultCompared with CK， the treatment groups showed decrease in content of malondialdehyde in the leaves （P<0.05）， particularly S7 （content was only about 1/3 that of the CK）. The leaf area， photosynthetic parameters， photosynthetic pigment content， soluble sugar content， soluble protein content， and activity of superoxide dismutase （SOD）， peroxidase （POD）， and catalase （CAT） in leaves of the treatment groups were all improved. Among them， the leaf area， soluble sugar content， and soluble protein content were the highest in S7， which were 2.8， 2.1， and 2.2 times that of the CK， respectively. SOD activity peaked in S6 （2.9 times higher than that in the CK） and the highest activity of POD and CAT was detected in S5 （1.5 times and 2.1 times， respectively higher than that in the CK）.ConclusionInoculation with different organophosphate-solubilizing bacteria or compound bacteria can promote the growth and development of P. polyphylla var. yunnanensis and improve its resistance to stresses. The combination of B. mycoides and B. proteolyticus and the combination of the three achieved the have the best effect. This study provides a reference for the selection of bacterial fertilizers for artificial cultivation of P. polyphylla var. yunnanensis.
Keywords：Paris polyphylla var. yunnanensis;organophosphate-solubilizing bacteria;photosynthesis;physiological and biochemical properties;compound bacteria
Abstract：ObjectiveTo investigate the effects of the inoculation of potassium-solubilizing bacteria on the rhizosphere soil microenvironment of Paris polyphylla var. yunnanensis.MethodThe effects of different potassium-solubilizing bacteria on the physical and chemical properties， microbial community structure， and soil enzyme activity in the rhizosphere soil of P. polyphylla var. yunnanensis were investigated by pot planting at room temperature. The correlation of various indexes was analyzed.ResultThe inoculation with different potassium-solubilizing bacteria could significantly affect the physical and chemical properties of rhizosphere soil of P. polyphylla var. yunnanensis. The mass fractions of available nitrogen， available phosphorus， and available potassium were 24.5-90.5 mg·kg-1， 2.53-25.9 mg·kg-1， and 132-312 mg·kg-1， respectively， and the soil pH was 7.08-7.75， which were in line with the optimal ranges of P. polyphylla var. yunnanensis planting. The inoculation of different potassium-solubilizing bacteria could affect the number of bacteria， actinomycetes， and fungi in rhizosphere soil to varying degrees. The transformation of soil from "fungal type" to "bacterial type" marks the improvement of soil fertility. It also affected the enzyme activity of rhizosphere soil， and the activities of neutral phosphatase， protease， and polyphenol oxidase showed an increasing trend. The correlation analysis showed that the number of bacteria was negatively correlated with the number of fungi （r=-0.856， P<0.01）， positively correlated with the number of actinomycetes， the content of available nitrogen and available potassium， and negatively correlated with soil pH.ConclusionThe inoculation of potassium-solubilizing bacteria can effectively improve the content of available potassium， available nitrogen， available phosphorus， and other nutrients in the rhizosphere soil of P. polyphylla var. yunnanensis， improve soil fertility， alleviate the continuous cropping obstacles of P. polyphylla var. yunnanensis， and lay a theoretical foundation for the green and sustainable development of P. polyphylla var. yunnanensis.
Keywords：Paris polyphylla var. yunnanensis;potassium-solubilizing bacteria;rhizosphere soil;physical and chemical properties;microbial community structure;soil enzyme
Abstract：ObjectiveTaking Chuanxiong Chatiaosan prescription as the carrier， by comparing the differences of volatile components in Chuanxiong Rhizoma with single decoction pieces and compatible prescription of different decoction pieces， the differences of material basic connotation of different formulations of Chuanxiong Chatiaosan were revealed from the aspects of processing （raw and wine-processed products）， compound compatibility and dosage form （powder and decoction）.MethodThe volatile oil was extracted from different decoction pieces of Chuanxiong Rhizoma， Chuanxiong Chatiaosan and its decoction with different decoction pieces of Chuanxiong Rhizoma by steam distillation， the main components and their relative contents were identified by gas chromatography-mass spectrometry （GC-MS）.ResultA total of 25 volatile components were identified from different processed products of Chuanxiong Rhizoma， including 11 monoterpenoids， 4 phenols， 3 sesquiterpenoids， 3 phthalides， 2 ketones and 2 olefins， the contents of α-pinene， β-pinene， 3-butylphthalide and others increased after the raw products was processed with wine. A total of 85 constituents were identified from Chuanxiong Chatiaosan with different decoction pieces， including 31 monoterpenoids， 23 sesquiterpenoids， 5 alcohols， 5 aldehydes， 4 phenols， 4 phthalides， 3 ethers， 3 ketones， 1 olefin， 1 organic acid， 2 esters and 3 other compounds. A total of 22 components， including 9 sesquiterpenoids， 3 phthalides， 2 phenols， 6 monoterpenoids， 1 aldehyde and 1 alkane， were identified from the decoction of Chuanxiong Chatiaosan with different processed products.ConclusionThere was no significant difference in the composition between raw products and wine-processed products of Chuanxiong Rhizoma either in single decoction pieces or in compatibility prescription， but the relative content changed to some extent， and the wine-processed products was the most obvious. There was a great difference in the composition of volatile components between the Chuanxiong Chatiaosan and its decoction. The volatile components， such as isopulegol， isocalamendiol and safrole， were not found in the decoction. Components in Chuanxiong Rhizoma processed with wine will change with the addition of yellow rice wine， and volatile components can reflect the difference between decoction pieces and prescriptions of the wine-processed products.
Keywords：volatile components;gas chromatography-mass spectrometry （GC-MS）;Chuanxiong Chatiaosan;compatibility;processing;stir-frying with wine;decoction
Abstract：ObjectiveTo investigate the intestinal absorption characteristics of multi-index components in Danggui Buxuetang with drug absorption simulating system （DASS） established by everted intestinal sac model.MethodThe intestinal absorption solution at different time points after administration of Danggui Buxuetang was collected and detected by high performance liquid chromatography （HPLC）， acetonitrile （A）-0.2% glacial acetic acid solution （B） was used as the mobile phase for gradient elution （0-16 min， 15%-23%A； 16-20 min， 23%-28%A； 20-25 min， 28%-30%A； 25-30 min， 30%A； 30-35 min， 30%-65%A； 35-45 min， 65%-95%A）， the detection wavelength was 302 nm. HPLC fingerprint of intestinal absorption solution was established and the common peak was calibrated， and the relative cumulative absorption rate of each index component was calculated. The relative cumulative absorption curves of components were fitted with various mathematical models by DDSolver 1.0 to explore the absorption law of different components.ResultThe absorption process of C2 （calycosin-7-glucoside） and C6 in Danggui Buxuetang was in line with zero-order equation， C9 was best fitted by Weibull equation， and the remaining 7 components were in line with Makoid-Banakar equation. C1 with C2， C3， C5， C7 and C10， C2 with C5 and C7， C3 with C4， C5， C7 and C10， C4 with C6 and C10， C5 with C7， C6 with C10， C7 with C10， C8 with C9 were absorbed simultaneously during the absorption process. With the prolongation of time， the overall cumulative absorption rate of Danggui Buxuetang increased. At 120 min， the overall cumulative absorption rate of Danggui Buxuetang exceeded 38%， and reached 49.14% at 180 min.ConclusionTen ingredients in Danggui Buxuetang are absorbed in the jejunum， but absorption law of various components is different， which shows that the intestinal absorption of compound preparations of traditional Chinese medicine （TCM） has multiple characteristics. Intestinal absorption study of TCM compound preparations with chemical composition as the index can reveal some of its absorption law， but it is not complete.
Abstract：ObjectiveChemical components in ethanol extract of Cyclocarya paliurus dried leaves were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UHPLC-Q-TOF/MS）.MethodAn Agilent Poroshell 120 EC-C18 column （3.0 mm×100 mm， 2.7 μm） was used with 0.1% formic acid aqueous solution （A）-acetonitrile （B） as the mobile phase for gradient elution （0-26 min，2%-18%B； 26-60 min， 18%-72%B； 60-70 min， 72%-100%B； 70-71 min， 100%-2%B； 71-72 min， 2%B）， and the flow rate of 0.4 mL·min-1 and injection volume of 3 μL. The electrospray ionization （ESI） was used in positive and negative modes， and detection range was m/z 50-1 100. The collected data were processed by Agilent MassHunter workstation. According to the retention time and MS information of each compound， combined with existing literature and MS database information， the compounds were identified and analyzed for the fragmentation rule.ResultA total of 52， 55 components were identified in the positive and negative ion modes， respectively. Among them， 14 flavonoids， 3 triterpenoids， 15 organic acids and 20 other compounds were identified under positive ion mode， while 18 flavonoids， 9 triterpenoids， 18 organic acids and 10 other compounds were identified under the negative ion mode. By summarizing the positive and negative ion modes and removing the common compounds， 87 compounds were identified， including 22 flavonoids， 27 organic acids， 11 triterpenoids and 27 other compounds.ConclusionUHPLC-Q-TOF/MS can be used to quickly analyze the chemical constituents in C. paliurus dried leaves. 1-Kestose and 18β-glycyrrhetinic acid and other components related to hypoglycemic activity of this herb are identified for the first time， which can provide reference for clarifying the pharmacodynamic substance basis of C. paliurus dried leaves.
Abstract：ObjectiveTo investigate the effects and mechanism of quercetin on experimental autoimmune uveitis （EAU） by regulating the Wnt/β-catenin signaling pathway.MethodThe regulatory relationship between quercetin and EAU was preliminarily determined by network pharmacology. The model was identified by enzyme-linked immunosorbent assay（ELISA） and clinical grading score. The important inflammatory factors， including interleukin（IL）-6 and tumor necrosis factor（TNF）-α in the signaling pathway were detected by ELISA. The binding of important targets in the pathway was verified by molecular docking. The protein and mRNA expression levels of related targets in the signaling pathway were detected by Western blot and Real-time polymerase chain reaction（Real-time PCR）， respectively.ResultAs evaluated by ELISA and the clinical grading score， the model was properly induced. The results of ELISA showed that the levels of IL-6 and TNF-α were the highest in the model group and the dimethyl sulfoxide （DMSO） group， and decreased after medium- and high-dose drug interventions， but the changing tend was the same. Molecular docking showed that the binding energies of quercetin to β-catenin and LRP6 were ideal. Western blot revealed that the expression of β-catenin and LRP6 was the highest in the model group， and decreased with drug intervention at different doses， but the changing trend was the same. Besides， there was no significant difference between the low-dose group and the high-dose group. Real-time PCR results showed that the expression of β-catenin，MYC，AXIN2， and TCF was the highest in the model group，the lowest in the high-dose group， and decreased in the low-dose group. There was no significant difference between the high-dose group and the low-dose group.ConclusionQuercetin can reduce the inflammatory expression of EAU and relieve the pain of patients by regulating the Wnt/β-catenin signaling pathway.
Abstract：ObjectiveTo predict the molecular mechanism of Erxian decoction and Wenshen prescription （modified Erxian decoction） in the treatment of depression based on network pharmacology and explore the feasibility of Wenshen prescription in the treatment of depression by comparing the efficacy and mechanism of the two decoctions based on a depression model induced by maternal separation combined with chronic restraint stress.MethodActive components and targets of Erxian decoction and Wenshen prescription were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Targets related to depression were screened out from databases such as GeneCards， Online Mendelian Inheritance in Man database （OMIM）， and DrugBank. Common targets of drugs and disease were obtained and imported to Cytoscape 3.8.2 to plot the drug-active component-target-disease network. STRING platform was used to construct a protein-protein interaction （PPI） network and core targets and related core components were screened out. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） functional enrichment analysis were performed on common targets through Metascape platform. The depression model was induced in mice by maternal separation combined with chronic restraint stress. From the 21st day of maternal separation （PD21） to the 111th day of restraint stress completion （PD111）， mice were fed with the diet mixed with Erxian decoction or Wenshen prescription for intervention. The depressive state of mice was evaluated according to the sucrose preference test， tail suspension test， open field test， and elevated O-maze test. The expression of ionized calcium-binding adapter molecule 1 （Iba1） in the microglia was observed by immunohistochemistry （IHC）. Western blot and Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression levels of protein kinase B1（Akt1）， brain-derived neurotrophic factor （BDNF）， postsynaptic density-95 （PSD95）， and synaptophysin （Syn）.ResultA total of 126 and 118 targets of Erxian decoction and Wenshen prescription in the treatment of depression were screened out， with only eight more targets of Erxian decoction than Wenshen prescription. The two decoctions shared the same core targets， mainly including Akt1， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）. KEGG pathway enrichment analysis predicted that Erxian decoction and Wenshen prescription mainly treated depression through the phosphatidylinositol-3 kinase （PI3K）/Akt signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and neuroactive ligand-receptor interaction pathway. Animal experiments showed that compared with the results in the model group， Erxian decoction and Wenshen prescription could up-regulate the sucrose preference index， prolong the time spent in the central zone， increase the number of crossings， prolong the time spent in opened arm， increase the number of crossings in the opened arm， elevate the expression levels of p-Akt1， BDNF， PSD95， and Syn （P<0.05， P<0.01）， shorten the immobility time of tail suspension， and reduce the expression level of Iba-1 in the hippocampal microglia （P<0.05， P<0.01）. No significant difference between the two decoctions was found.ConclusionUnder the pathogenesis and syndrome law of depression dominated by kidney yang deficiency， Wenshen prescription modified from Erxian decoction is feasible in the treatment of depression. The mechanism may be attributed to the fact that both decoctions can improve neuroinflammation and synaptic plasticity in the hippocampus by affecting Akt1， IL-1β， IL-6， TNF-α， and other core targets and regulating the PI3K/Akt， MAPK， and neuroactive ligand-receptor interaction signaling pathways.
Abstract：Because of the frequent occurrence of epidemics in Jiangnan since ancient times， the local medical schools have accumulated rich experience in epidemic prevention， among which Yushan medical school， Wumen medical school， and Qiantang medical school are famous. The physicians have inherited the theory in Treatise on Cold Damage Diseases and developed the therapies for febrile diseases. Adhering to the idea of integrating cold and febrile diseases， the physicians in Jiangnan flexibly adapt ZHANG Zhongjing's theory by combining regional climate， patient physique and other factors to explain the pathogenesis， which is of great significance for the prevention and treatment of epidemics. Therefore， traditional Chinese medicine （TCM） has demonstrated good curative effect on coronavirus disease-2019 （COVID-19） in China. However， the SARS-CoV-2 variants （Delta and Omicron） characterized by strong infectivity， pathogenicity， and immune escape capacity keep emerging， which bring great challenges to the global prevention and control of this pandemic. To this end， we studied the ways of Jiangnan medical school for the prevention and treatment of epidemics， reviewed the evolution of TCM treatment protocols for COVID-19， and summarized China's experience in fighting against the emerging SARS-CoV-2 variants. Further， we explored the measures of TCM in treating SARS-CoV-2 variants from prevention， treatment， and rehabilitation according to the theory for epidemic prevention of Jiangnan medical school. This paper provides reference for the prevention and treatment of emerging SARS-CoV-2 variant and facilitates the development of TCM epidemiology.
Keywords：coronavirus disease- 2019 （COVID-19）;SARS-CoV-2 variants;traditional Chinese medicine;Jiangnan medical school;prevention， treatment， and recuperation
Abstract：Chronic renal failure （CRF） is generally characterized by micro-inflammatory state， which can aggravate the CRF process in severe cases， leading to the deterioration of renal function， malnutrition， anemia and other complications. Therefore， it is of great significance to improve the micro-inflammatory state of CRF. "Deficiency of Qi and stagnation" is the basic pathogenesis of the micro-inflammatory state of CRF， which runs through the whole process of the disease and affects the formation and outcome of CRF in different forms. Traditional Chinese medicine （TCM） has unique advantages in improving the micro-inflammatory state and enhancing the immunity of the body due to its advantages of syndrome differentiation and treatment， strengthening the righteousness and eliminating pathogenic factors. Therefore， the author systematically sorted out the relationship between micro-inflammatory state and CRF， understanding of micro-inflammatory state of CRF and its prevention and treatment of TCM by referring to relevant literature， based on the theory of "deficiency of Qi and stagnation"， and proposed that spleen and kidney failure （deficiency of Qi） is the origin of micro-inflammatory state of CRF， and blood stasis and poisonous evil （stagnation） is the target of its onset. Deficiency of Qi and stagnation adhered to each other， acted as cause and effect， and developed in a spiral manner throughout the development of the disease. TCM has the effects of nourishing the spleen and kidney， removing blood stasis and turbidity. By down-regulating C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor alpha （TNF-α） and other micro-inflammatory indicators， it can eliminate the pathological wastes derived from spleen and kidney deficiency， reduce the micro-inflammatory state， restore the balance of Yin and Yang in the body to achieve the purpose of eliminating pathogens and protecting renal function， providing guidance for the clinical treatment of CRF.
Keywords：chronic renal failure （CRF）;micro-inflammatory state;deficiency of Qi and stagnation;traditional Chinese medicine;inflammatory factors;mechanism of action;complications
Abstract：Tumor has become one of the major diseases threatening human health at present. Conventional therapies for tumor have serious side effects and are prone to drug resistance， while new therapies are expensive and impose a heavy burden on patients. Chinese herbs effective in the treatment of tumor contain a variety of natural active ingredients， and many anti-tumor drugs used in clinical practice are derived from Chinese herbs. Polysaccharides， ubiquitous in Chinese herbs， are easy to extract and have antitumor， antiviral， and antioxidant activities. Studies have demonstrated that the polysaccharides from Chinese herbs have significant anti-tumor effect and are characterized by multi-target and multi-mechanism functioning， which can avoid the development of drug resistance， exhibiting a great research value and the potential to be developed into novel anti-tumor drugs. Their anti-tumor mechanisms mainly include the inhibition of tumor proliferation， promotion of apoptosis， induction of autophagy， influence on cell cycle， inhibition of tumor angiogenesis， modulation of epithelial-mesenchymal transition （EMT） and immunity， promotion of tumor oxidative stress， and regulation of phosphatidylinositol 3-kinase/ protein kinase B （PI3K/Akt）， Toll-like receptor 4 （TLR4）， mitogen-activated protein kinase/nuclear factor-kappa B （MAPK/NF-κB）， adenosine 5'-monophosphate （AMP）-activated protein kinase/mechanistic target of rapamycin （AMPK/mTOR）， epidermal growth factor receptor/extracellular signal-regulated kinase （EGFR/ERK）， p53， and Wnt/β-catenin signaling pathways.
Abstract：Nasal preparations have unique advantages in drug delivery and are widely used in the treatment of local and systemic diseases. Nasal administration of traditional Chinese medicine （TCM） has a long history in China. In recent years， nasal preparations of TCM have attracted wide attention. Based on the information about nasal preparations of TCM from the database of National Medical Products Administration （NMPA）， Yaozh.com and China National Knowledge Internet （CNKI） in the recent 30 years， the formulation， the listed products， commonly used TCM， pharmaceutical excipients， clinical application and safety research of modern nasal preparations of TCM were summarized and expounded. Focusing on many problems in the development of modern nasal preparations of TCM， such as inaccurate dosage of some products， incomplete quality standard system of pharmaceutical excipients， imperfect safety evaluation， lack of research and development of nasal drug delivery devices and so on， the possible solutions and prospects were put forward from the aspects of optimizing the extraction and separation process of TCM， the quality control and application method of pharmaceutical excipients， the development of new dosage forms， the safety evaluation of nasal administration of TCM， and the design and development of nasal administration devices. The aim is to provide ideas for the development of nasal preparations of TCM and provide scientific basis for its sustainable utilization.
Keywords：nasal preparations;nasal administration;pharmaceutical excipients;clinical trials;new dosage forms;traditional Chinese medicine （TCM）;safety evaluation
Abstract：Diabetes mellitus （DM） is a metabolic disease mainly characterized by chronic hyperglycemia and has multiple etiologies. The complications of DM， such as coronary atherosclerosis， nephropathy， foot disease and cardiac dysfunction， have high morbidity， disability rate and mortality. DM and its complications have a long course of disease and are easy to relapse， which are difficult to be cured， seriously affecting people's life and health. NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is an important component of inflammatory response and innate immune system. The inflammatory cascade induced by NLRP3 activation is involved in the occurrence and development of DM as well as its complications by releasing inflammatory factors， damaging endothelial cells and affecting metabolic stress. Therefore， as the core of the inflammatory response， NLRP3 may provide a new target for the treatment of DM and its complications. Traditional Chinese medicine plays a key role in the treatment of DM and its complications， and has a regulatory effect on NLRP3. Thus it has become a novel research strategy to prevent and treat DM and its complications via modulating NLRP3. However， at present， there are relatively scattered reports and a lack of systematic review on the role of traditional Chinese medicine in the treatment of DM and its complications from the perspective of NLRP3. As a result， this paper reviewed domestic and foreign literature in recent years and conducted the discussion from two aspects： the influence of NLRP3 on the occurrence and development of DM and its complications， and the progress of traditional Chinese medicine in intervening in DM and its complications through NLRP3. This paper provided reference for the research on the regulation of NLRP3 and a new direction for the treatment of DM and its complications.
Keywords：diabetes mellitus （DM）;NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome;diabetic nephropathy;atherosclerosis;traditional Chinese medicine
Abstract：Chronic renal failure （CRF）， a common outcome of various chronic kidney diseases， is characterized by retention of metabolites and toxins， water-electrolyte imbalance， acid-base disturbance， and various symptoms in diverse systems. The incidence and progression of this disease are influenced by many factors， particularly the change of intestinal flora. Previous research shows that the intestinal flora interacts with CRF. For CRF patients， the metabolic waste fails to be cleared in time due to the gradual decline of renal function and thus accumulates in vivo. Moreover， CRF changes the composition of intestinal flora， damages intestinal barrier， and accelerates the synthesis of intestinal uremic toxins and the accumulation in blood. As a result， the renal injury is aggravated. The imbalance of intestinal flora can induce acute kidney injury， increase cardiovascular complications， stimulate immune inflammatory responses， and thus aggravate the progression of CRF. Microbiota-targeted therapy for CRF has become the research focus. According to traditional Chinese medicine， kidney disease is related to the intestine and kidney disease should be treated from the intestine. Spleen and kidney are in the closest relationship with the pathogenesis of CRF and the intestinal flora. Chinese medicine， which features multiple targets， multiple effects， and multiple components， acts on the "gut-kidney axis". It is thus superior in the clinical treatment of CRF and the regulation of intestinal flora. To be specific， it intervenes in intestinal flora to delay the process of CRF. In this paper， based on the correlation of traditional Chinese medicine theory with intestinal flora and CRF， this paper reviewed the interaction between intestinal flora and CRF and traditional Chinese medicine intervention in the intestinal flora for the treatment of CRF， which is expected to serve as a reference for the clinical treatment of this disease and the drug development.
Keywords：intestinal flora;chronic renal failure;interaction;traditional Chinese medicine
Abstract：Migraine is a common neurovascular disorder manifested by recurrent severe headaches on one or both sides， occasionally accompanied by nausea， vomiting， photophobia， and phonophobia. It has the characteristics of recurrent attacks and family inheritance. Traditional Chinese medicine （TCM） believes that migraine belongs to the category of "head wind"， which is mostly caused by external wind and is related to the internal stirring of liver wind. Sanpiantang comes from the Record of Syndorme Differentiation·Headache （Bianzhenglu·Toutongmen） created by the physician CHEN Shiduo of the Qing Dynasty. It is composed of Chuanxiong Rhizoma， Angelicae Dahuricae Radix， Pruni Semen， Cyperi Rhizoma， Bupleuri Radix， White Mustard Seed， and Glycyrrhizae Radix et Rhizoma， with the functions of moving Qi to release pain， activating blood and resolving stasis， which is commonly used for the treatment of migraine in clinic. Current clinical studies on the application of Sanpiantang to the treatment of migraine mostly used modified Sanpiantang， either alone or in combination with western medicine/acupuncture. The results of these clinical trials showed that Sanpiantang could significantly lower migraine score， pain visual analog scale and endothelin level， reduce the frequency of painkiller use， and remarkably alleviate migraine symptoms， with few side effects. The animal experiments focused on exploring the mechanism of action of modified Sanpiantang from different anatomical levels of migraine， which mainly included reducing nitric oxide （NO） and nitric oxide synthase （NOS）， reduceing the release of neurotransmitters such as 5 -hydroxyline (5-HT) and neurotipides (NPY)， suppressing neuronal excitation， and blocking the transmission of nociceptive pathways， thereby promoting cerebral blood flow， regulating neurotransmitters and preventing migraine. Based on the pathogenesis of migraine， this paper systematically reviewed the latest progress in clinical application and experimental research of modified Sanpiantang， and summarized its mechanism of action of preventing and treating migraine， which provided new ideas for clinical treatment of migraine.
Abstract：Population aging has become a major feature of the demographic structure of today's society， and anti-aging is currently one of the major areas and hot spots of medical research. Kidney deficiency causes aging is the basic theory of aging in TCM， and kidney tonics have a long history of improving physiological functions and significantly alleviating aging-related diseases. However， the formulation of kidney tonics is complicated and the mechanism of action is still unclear. It is difficult to precisely analyze the targets of disease action and metabolic pathways. The kidney tonic herb Epimedium has the effect of tonifying the kidney and augmenting yang， and is not only used to treat diseases related to kidney deficiency and aging， but also has unique advantages in the treatment of mental and emotional diseases. Modern pharmacological studies have proved that Icarrin， a monomeric component of Epimedium， can produce a wide range of biological functions on cardiovascular system， exercise system， reproductive system， and nervous system， with strong antioxidant， free radical scavenging， and repair of mitochondrial DNA damage， which can anti-aging， anti-depression， and improve immunity， etc. In this paper， we searched databases such as CNKI， Pubmed， Wanfang database， Wipu Chinese journal service platform， and web of science to review the research on Icarrin， a monomeric ingredient that has both anti-aging and anti-depression effects， in order to provide a basis for further research on anti-depression and anti-aging in Chinese medicine.
Keywords：icarrin;anti-aging;anti-depression;mechanism of action;traditional Chinese medicine