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Issue 2 ， 2019
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Effect of Saposhnikoviae Radix-Mume Fructus Drug-containing Serum in Regulating Phenotypic Transformation of Airway Smooth Muscle Cell Proliferation Model
Abstract：Objective:To observe the effect of Saposhnikoviae Radix-Mume Fructus containing-serum in regulating the phenotypic transformation of airway smooth muscle cells (ASMCs) proliferation model, in order to explore the mechanism of combined administration of "Saposhnikoviae Radix, Mume Fructus" in inhibiting airway remodeling, and reveal the compatibility mechanism of traditional Chinese medicine.Method:The proliferation model of ASMCs was established by platelet derived growth factor (PDGF) induction. The rats were given normal saline, Saposhnikoviae Radix-Mume Fructus, Saposhnikoviae Radix-Mume Fructus(15.425, 15.425, 30.85 g·kg-1·d-1) to prepare drug serum respectively. Four generations of logarithmic phase human bronchial smooth muscle cells (HBSMC) were collected and divided into blank control group, cell model group, normal rat serum group and normal rat serum cell model group, hormone intervention group, Saposhnikoviae Radix serum group, Mume Fructus serum group, Saposhnikoviae Radix-Mume Fructus serum group. The cells were given corresponding treatment. Immunofluorescence staining and Western blot were adopted to detect ASMCs deflating marks protein α-actin and osteopontin (OPN) expressions, and phenotypic transformation was observed; the levels of vascular endothelial growth factor(VEGF), transforming growth factor-β(TGF-β) and interleukin-6(IL-6) secreted by ASMCs were detected by enzyme linked immunosorbent assay (ELISA).Result:Compared with blank group and normal rat serum group, the fluorescence intensity and protein expression of α-actin in model group and normal rat serum cell model group were low, whereas the fluorescence intensity and protein expression of OPN were high, and the concentrations of VEGF, TGF-β and IL-6 increased significantly (P<0.05). Compared with model group and normal rat serum cell model group, Saposhnikoviae Radix-Mume Fructus serum group and hormone intervention group could significantly enhance the fluorescence intensity and protein expression of alpha-actin, decrease the fluorescence intensity, protein expression of OPN and concentrations of VEGF, TGF-β and IL-6 (P<0.05).Conclusion:The combined administration of "Saposhnikoviae Radix-Mume Fructus" has an inhibitory effect on airway remodeling, which may be related to the inhibition of the transformation of ASMCs from contractile phenotype to synthetic phenotype, so as to reduce the release of active substances, such as VEGF, TGF-β and IL-6.Keywords：Saposhnikoviae Radix;Mume Fructus;asthma;airway smooth muscle cells;airway remodeling;cell phenotype- 12
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
UPLC-Q-TOF-MS/MS Analysis of Brain and Blood Absorption Components of Buyang Huanwu Tang After Intragastric Administration
Abstract：Objective:To analyze and identify the brain and blood absorption components of rats after intragastric administration of Buyang Huanwu Tang(BYHWT).Method:The brain tissue, plasma of normal rats and the cerebral ischemia-reperfusion rats were analyzed by UPLC-Q-TOF-MS/MS.The prototype components in BYHWT were identified according to retention time, accurate relative molecular weight, primary and secondary mass spectrometry data.Result:After the administration of BYHWT, five compounds were found to enter the normal brain tissue through the blood-brain barrier and identified as calycosin-7-glucoside, albiflorin, formononetin-7-O-β-D-glucoside-6″-O-acetyl, safflower yellow A and astragaloside A; two compounds penetrated the blood-brain barrier and entered modeling brain tissue, and they were identified as calycosin-7-glucoside and formononetin-7-O-β-D-glucoside-6″-O-acetyl; seven compounds entered normal plasma and were identified as calycosin-7-glucoside, albiflorin, hydroxysafflor yellow A, et al; three compounds entered model plasma and identified as calycosin-7-O-β-D-glucoside-6″-O-acetyl, 6″-O-acetyl-(6αR, 11αR)-9, 10-dimetho-xypterocarpan-3-O-β-D-glucoside and formononetin-7-O-β-D-glucoside-6″-O-acetyl.Conclusion:BYHWT has different pharmacological material basis in normal and cerebral ischemia-reperfusion rats.Keywords：Buyang Huanwu Tang;calycosin-7-glucoside;albiflorin;cerebral homogenate;formononetin-7-O-β-D-glucoside-6″-O-acetyl;plasma;prototype components- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09
Compatibility
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Effect of Danggui Shaoyao San Drug-containing Serum on Expression of p-MLCⅡ and MLCⅡ Protein in HSC-T6 Cells Induced by ET-1
Abstract：Objective:To investigate the effect of endothelin-1 (ET-1) on the expression of phosphorylated myosin light chain Ⅱ(p-MLCⅡ)and myosin light chain Ⅱ(MLCⅡ)protein in rat hepatic stellate cells HSC-T6 and explore the intervention effect of Danggui Shaoyao San(DSS)drug-containing serum.Method:After HSC-T6 cells were seeded, DMEM and blank rat serum with final concentrations of 2.5%, 5%, 10%, 15% and 20% were added to each well. The viability of HSC-T6 cells was determined by methyl thiazolyl tetrazolium(MTT) assay to screen the suitable serum concentration range. The cells were divided into blank serum control group (5%, 10%, 15%) and DSS drug-containing serum group (5%, 10%, 15%). ELISA was used to detect the content of ET-1 in cell culture supernatant under basic state. The cells were divided into blank serum control group (10%), DSS drug-containing serum low (5%), medium (10%) and high dose (15%) groups. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to detect the level of ET-1 mRNA in cell culture supernatant under basic state. The cells were divided into blank serum control group (10%), model group (10%), DSS drug-containing serum low (5%), medium (10%), high dose (15%) groups and Y-27632 inhibitor group (100 μmol·L-1). Except the blank serum control group, the other groups all received 10 nmol·L-1 ET-1 to induce HSC-T6 cells. Western blot was used to detect the expression of p-MLCⅡ and MLCⅡ in HSC-T6 cells induced by ET-1.Result:Serum concentrations of 5%, 10% and 15% were used as drug-containing serum concentrations. As compared with the blank serum control group, the DSS drug-containing serum group significantly reduced the relative content of ET-1 and ET-1 mRNA in the basic state (P<0.05, P<0.01). As compared with the blank serum control group, the expression of p-MLCⅡ and MLCⅡ protein in the model group was significantly increased (P<0.01); DSS drug-containing serum groups and Y-27632 inhibitor group can significantly down-regulate p-MLCⅡ and MLCⅡ protein expression (P<0.05, P<0.01).Conclusion:DSS drug-containing serum may down-regulate the expression of p-MLCⅡ and MLCⅡ by down-regulating the content of ET-1 and inhibiting the autocrine of ET-1.Keywords：Danggui Shaoyao San;drug-containing serum;HSC-T6 cells;endothelin-1(ET-1);p-myosin light chain(MLC)Ⅱ- 12
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Effect of Dahuang Mudan Tang in Triggering Receptor Expressed on Myeloid Cells-1 in Intestinal Tract in Rats with Septic Acute Intestinal Dysfunction
Abstract：Objective:To investigate whether the therapeutic effect of Dahuang Mudan Tang on septic acute intestinal dysfunction in sepsis ratsis related to the regulation of expression of triggering receptor expressed on myeloid cells-1(TREM-1).Method:Totally 100 male SD rats were injected intraperitoneally with lipopolysaccharide (LPS) at a dose of 4.5 mg·kg-1to build sepsis model. The sepsis model rats were randomly divided into five groups: model group, glutamine group (3.75 g·kg-1), low, medium, high-dose Dahuang Mudan Tang group(7.5, 15, 30 g·kg-1), and another 10 normal rats were selected as normal group. Seven days later, 2 mL suspension (100 mg lactulose and 50 mg mannitol) was orally administrated by gavage, and 24 h urinewas collected. The ratio of lactulose to mannitol in urine (L/M) was detected by HPLC with pulsed electrochemical detection (HPLC-PED). Serum citrulline concentrationsin blood and ileum were determined by HPLC.Enzyme linked immunesorbent assay (ELISA) was used to detect the concentrations of triggering receptor expressed on myeloid cells-1(TREM-1), tumor necrosis factor-α(TNF-α), intestinal fatty acid binding protein(iFABP) and D-lactic acid.Real-time PCR was used to detect the mRNA expressions of TREM-1, Toll-like receptors2(TLR2), Toll-like receptors 4(TLR4), myeloid cell differentiation protein(MyD88), nuclear transcription factor-κB(NF-κB). Electron microscopy was used to observe the pathological changes of intestinal mucosa injury.Result:Compared with normal group, the serum concentrations of TREM-1, TNF-α, iFABP, D-lactate; the ratio of lactulose to mannitol in urine (L/M)and the expressions of TREM-1, TLR2, TLR4, MyD88, NF-κB mRNA in model group were increased obviously(P<0.05, P<0.01); citrulline concentration was decreased obviously(P<0.05); the lengths of the villus and thicknesses of the mucosal layer were decreased obviously(P<0.05); the Chiu score was increased obviously(P<0.01). Compared with model group, the expressions of TREM-1, TLR2, TLR4, MyD88, NF-κB mRNA, and the serum concentrations of TREM-1 and TNF-α in all medication administration groups were decreased obviously(P<0.05), with no difference between these groups.Compared with model group, the serum concentrations of iFABP, D-lactate, L/M, the Chiu scorein glutamine group, medium-dose Dahuang Mudan Tang group and high-dose Dahuang Mudan Tang group were decreased obviously(P<0.05), lengths of villus and thicknesses of mucosal layers were increased obviously(P<0.05); and the citrulline concentrations were increased obviously(P<0.05). There was no difference between the three groups.Conclusion:Dahuang Mudan Tang can effectively treat SAID in rats, and its mechanism may be realized by regulating the expression of TREM-1 and relieving intestinal inflammation of intestinal tract.Keywords：Dahuang Mudan Tang;sepsis;acute intestinal dysfunction;intestinal tract;triggering receptor expressed on myeloid cells-1- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Effect of Yingyang Gongji Wan Contained Serum on Inhibiting HepG2 Cell Proliferation and Invasion, and Inducing Apoptosis
Abstract：Objective:To investigate the effect of Yingyang Gongji Wan (YYGJ) on hepatoma cell line HepG2, and provide evidence for clinical application.Method:YYGJ-contained rats serum was prepared. Then the inhibiory rate of cells was detected by methye thiazolye telrazlium (MTS) method in both YYGJ group and blank group. Apoptosis of HepG2 was detected by TdT-mediated dUT nick-end labeling (TUNEL) method in blank group, YYGJ group, and 5-fluorouracil (5-FU) group. The mRNA expression and protein expression levels of E-cadherin, Vimentin, metalloproteinase-2 (MMP-2) and Smad4 were detected by Real-time quantitative PCR (Real-time PCR) and Western blot respectively. The invasion ability of HepG2 cells was detected by cell migration assay (transwell).Result:YYGJ-contained serum inhibited the proliferation of HepG2 cells in a time and concentration-dependent manner. As compared with blank group, the inhibitory rate was increased in 5%, 10%, and 20% YYGJ-contained serum groups on the third day (P<0.05), and apoptosis rate was also increased significantly in YYGJ and 5-FU groups (P<0.05), but there was no significant difference between 50% YYGJ group and 5-FU group in apoptosis rate. As compared with blank group, the mRNA and protein expression levels of E-cadherin and Smad4 were increased significantly, while Vimentin and MMP-2 mRNA and protein expression levels were decreased significantly in YYGJ and 5-FU groups (P<0.05). HepG2 cell invasive ability was decreased significantly in YYGJ and 5-FU groups as compared to blank group (P<0.05), but there was no significant difference between 50% YYGJ group and 5-FU group.Conclusion:YYGJ-contained serum can inhibit the proliferation of HepG2 cells, induce apoptosis, regulate epithelial-mesenchymal transition (EMT)-related E-cadherin, Vimentin, MMP-2 and Smad4 genes and proteins, and decrease tumor invasion ability. The effect was similar to that of 5-fluorouracil. As a unique prescription, YYGJ can be used as a representative for the treatment of coldness and dampness syndrome of primary liver cancer and its anti-cancer mechanism should be further studied.Keywords：Yingyang Gongji Wan;primary liver cancer;HepG2 cell;epithelial-mesenchymal transition (EMT)- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09
Classic Prescriptions
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Effect of Processing with Vinegar on Hepatorenal Toxicity of Dichloromethane Site of Genkwa Flos
Abstract：Objective:To campare the hepatotoxicity on BRL and nephrotoxicity on NRK caused by dichloromethane site of Genkwa Flos before and after being processed with vinegar.Method:BRL of normal hepatocytes and NRK of normal renal cells in rats were selected as the subjects.Thiazolyl blue tetrazolium bromide method(MTT) was adopted to evaluate the effect of dichloromethane sites of raw and vinegar-processed products on cell activity of NRK and BRL.The levels or contents of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), glutathione(GSH), lactate dehydrogenase(LDH), blood urea nitrogen(BUN) were determined in cell culture supernatant and splitting supernatant for evaluation of their oxidative damage effect.Result:Compared with the blank group, dichloromethane site of raw products could obviously inhibit the cell activity of NRK and BRL, and increase the levels of AST, ALT, ALP and LDH(P<0.05, P<0.01) in BRL and decrease the content of GSH; meanwhile, it could obviously increase the levels of LDH and BUN(P<0.05, P<0.01) and decrease the content of GSH in NRK.Compared with corresponding dose group of raw products, vinegar-processed products could improve cell activity of NRK and BRL, and decrease the levels of AST, ALT, ALP and LDH in BRL and increase the content of GSH; also, it decreased the levels of LDH and BUN and increased the content of GSH in NRK.Conclusion:Processing with vinegar can attenuate the hepatotoxicity and nephrotoxicity on NRK and BRL caused by dichloromethane site of Genkwa Flos, it can improve hepatic and renal function and antioxidant capacity.Keywords：Genkwa Flos;processing with vinegar;NRK;BRL;reducing toxicity;hepatorenal cells;oxidative damage- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Preparation, Characterization and in Vitro and in Vivo Absorption Characteristics of Daidzein Nanosuspension Capsules
Abstract：Objective:To prepare daidzein nanosuspension capsules, and to investigate intestinal absorption and oral bioavailability by comparing with commercial daidzein capsules.Method:Daidzein nanosuspensions were prepared by precipitation method combined with high pressure homogenization, orthogonal design method was utilized to optimize its formulation.Daidzein nanosuspensions was characterized by X-ray powder diffraction(XRPD), Fourier transform infrared spectroscopy(FT-IR), transmission electron microscope(TEM), and indexes including mean particle size, polydispersity index(PDI), and Zeta potential.Intestinal absorption study was carried out to compare the accumulative permeated amount of daidzein from daidzein nanosuspensions and commercial daidzein capsules.Biodistribution of daidzein in gastrointestinal tract was investigated, and oral bioavailability was examined through pharmacokinetic study by HPLC.Result:The in vitro small intestinal absorption enhancement ratio of daidzein nanosuspension capsules was approximately 2.49-fold higher than that of commercial capsules(P<0.01). Biodistribution evaluation in gastrointestinal tract verified the bioadhesion of the nanosuspensions.Pharmacokinetic study calculated by DAS 2.0 revealed that the relative bioavailability of daidzein nanosuspension capsules was 294%.Conclusion:Daidzein nanosuspensions prepared by combined method can be applied to the production of capsules, which is beneficial to increase the absorption of drug in small intestine and improve its bioavailability after oral administration.Keywords：daidzein;nanosuspensions;capsules;high pressure homogenization technology;in vitro intestinal absorption;pharmacokinetics;bioavailability- 12
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09
Pharmacy and Processing
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Effect of Compound Phyllanthus urinaria Ⅱ(CPU Ⅱ) on Proliferation, Apoptosis and Autophagy of Hepatocellular Carcinoma Huh7 Cells
Abstract：Objective:To observe the effect and investigate the mechanism of compound Phyllanthus urinaria Ⅱ(CPU Ⅱ)on proliferation, apoptosis and autophagy of human hepatoma cell line Huh7.Method:Huh7 cells were cultured in vitro and divided into blank control group, high-dose CPU Ⅱ group (40 g·L-1), low-dose CPU Ⅱ group (20 g·L-1), and 5-FU group (0.04 g·L-1). Methye thiazolye telrazlium(MTT) assay was used to detect the inhibitory effect of CPU Ⅱ on proliferation of human hepatoma Huh7 cells. The apoptosis rate was observed by Annexin V-FITC/PI flow cytometry; the changes of autophagosomes in each group were observed by monodansylcadaverin (MDC) staining; Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was used to detect the mRNA expression of phosphatidylinositol 3-kinase (PI3K), Serine-threonine protein kinase 2(Akt2), B-cell lympoma-2(Bcl-2) and Microtubule-associated protein 1 light chian 3(LC3Ⅱ) and Western blot was used to detect the protein expression of Akt2 and LC3Ⅱ.Result:CPU Ⅱ(40, 20 g·L-1) significantly inhibited the hepatoma cell line Huh7 and induced apoptosis, with an apoptosis rate of 51.72% and 19.74% respectively, significantly higher than that of control group (P<0.01). After MDC staining, it was observed that a large number of fluorescent particles were distributed in the cytoplasm and nucleus of liver cancer cells under the effect of CPU Ⅱ. As compared with blank control group, the mRNA expression levels of PI3K, Akt2, and Bcl-2 were decreased significantly while the mRNA expression of LC3Ⅱ was increased significantly in CPU II high-and low-dose groups (P<0.01); the protein expression of Akt was significantly decreased while protein expression of LC3Ⅱwas significantly increased in CPU Ⅱ high-dose and low-dose groups (P<0.05, P<0.01).Conclusion:CPUⅡ had obvious inhibitory effect on the proliferation of hepatoma cell line Huh7, and the mechanism may be related to inhibiting the activation of PI3K/Akt signaling pathway to induce apoptosis and autophagy.Keywords：Phyllanthus urinaria Ⅱ;autophagy;proliferation;apoptosis;Huh7 cells- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Effect of Mangiferin on mRNA Expressions of Hepatic PRPS, PRPPAT and Cerebral HGPRT in Hyperuricemic Mice Induced by Potassium Oxonate
Abstract：Objective:To investigate the effect of mangiferin on the mRNA expression of phosphoribosylpyrohoosphate synthetase (PRPS), phosphate ribose pyrophosphate amide transferase (PRPPAT) in liver and hypoxanthine-guanine phosphate transfer enzyme (HGPRT) in brain of hyperuricemic mice induced by potassium oxonate.Method:Hyperuricemic mice were induced through intraperitoneal injection with uricase inhibitor potassium oxonate. The serum uric acid level was determined by the phosphotungstic acid method. The mRNA expression levels of PRPS and PRPPAT in liver as well as HGPRT in brain of hyperuricemic mice were measured by reverse transcriptase polymerase chain reaction (RT-PCR).Result:An intraperitoneal injection with potassium oxonate caused a marked increase in serum uric acid level, compared with normal control group (P<0.05). Intragastric administration with mangiferin at the doses of 1.5, 3.0, 6.0 mg·kg-1 was able to significantly reduce serum uric acid levels, compared with hyperuricemic control group (P<0.05, P<0.01); Moreover, the increase in the mRNA expression levels of PRPS and PRPPAT in liver, as well as the decrease in the mRNA expression of HGPRT in brain were observed in hyperuricemic control group, but with no statistically difference. Mangiferin has no impact on the mRNA expressions of PRPS, PRPPAT and HGPRT, compared with hyperuricemic control group.Conclusion:The hyporuricemic effect of mangiferin might not be related with PRPS, PRPPAT and HGPRT in therapeutic dose.Keywords：mangiferin;hyperuricemia;phosphoribosylpyrohoosphate synthetase (PRPS);phosphate ribose pyrophosphate amide transferase (PRPPAT);hypoxanthine-guanine phosphate transfer enzyme (HGPRT)- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Effect of Inula cappa on CYP450 Enzyme in Rats by Cocktail Probe Drugs
Abstract：Objective:To study on the effect of Inula cappa extract on the activities of six cytochrome P450(CYP450) enzymes in rats by Cocktail probe method.Method:Rats in the I. cappa high and low dose groups were given oral administration of active fractions of I. cappa at a dose of 8.127, 2.709 g·kg-1·d-1 of the material for 7, 14 d, repectively.Probe drugs(caffeine, midazolam, tolbutamide, omeprazole, metoprolol, chlorzoxazone) were simultaneously injected to rats after administration.Plasma was collected at different time after the administration of probe drugs.The plasma concentrations of these six probes were measured by UPLC-MS and their corresponding pharmacokinetic parameters were calculated with DAS 2.0.Result:Compared with the control group, only the apparent volume of distribution(V) of midazolam was increased; area under the curve(AUC0-t and AUC0-∞)and half-life period(T1/2) of caffeine, midazolam, tolbutamide and omeprazole were increased and the clearance rate(CL) of them was decreased in rats of I. cappa groups.But there were no differences in pharmacokinetic parameters of chlorzoxazone and metoprolol.Conclusion:I. cappa can reduce the enzymatic activities of CYP3A, CYP1A2, CYP2C9 and CYP2C19 in rats at different degree, among which CYP3A is the strongest.Keywords：Cocktail probe drug method;Inula cappa;active site;extract;cytochrome P450;drug interaction;midazolam- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Effect of Berberine on HCCLM3 Cells Apoptosis and Autophagy Under High Glucose Condition
Abstract：Objective:To explore the anti-tumor molecular mechanism of berberine (BBR)by observing and analyzing its effect on proliferation, apoptosis and autophagy-related gene expression for HCCLM3 cells under high glucose condition.Method:HCCLM3 cells were added into low, medium or high-concentration groups of glucose. It was found in cell counting kit-8(CCK-8)that the high concentration of glucose had the most obvious effect on HCCLM3 cells proliferation. Based on the above experimental result, HCCLM3 cells treated with high concentration of glucose was selected and then different concentrations of berberine (5, 10, 20, 30, 40, 50 μmol·L-1) was added for in vitro intervention for 24 h. Then the effect of each drug group on the proliferation of HCCLM3 cells were studied. At the same time, the control group of metformin was arranged. After that, the changes of apoptosis rate were observed by flow cytometry, and the expression levels of B-cell lymphoma-2(Bcl-2)and autophagy genes Atg5, Beclin1 were detced by Real-time polymerase chain reaction (Real-time PCR).Result:With the increase of glucose concentration, HCCLM3 cell had the strongest migration and proliferation ability in high glucose group (P<0.05). The inhibitory effect of BBR on the proliferation of HCCLM3 in high glucose culture was correlated with the concentration of BBR(5, 10, 20, 30, 40, 50 μmol·L-1), and the inhibition rate was 33.86%, 40.75% (P<0.05), 49.22%, 55.1%, 60.12%, and 61.42% respectively from low concentration to high concentration (P<0.01). The apoptosis rate was significantly increased with the increase of BBR concentration (P<0.01). The expression levels of Bcl-2, Atg5 and Beclin1 gene were significantly up-regulated in all intervening groups as compared with those in single high glucose group (P<0.05, P<0.01).Conclusion:BBR could inhibit the proliferation of HCCLM3 cells in high glucose environment. Its inhibition effect for HCCLM3 cells might be achieved by inducing apoptosis of the cells, regulating Bcl-2 and up-regulating the expression levels of autophagy gene Beclin1 and Atg5.Thus BBR plays an anti-tumor role through promoting autophagy in high glucose environment.Keywords：berberine;HCCLM3 cells;high glucose;apoptosis;autophagy- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Effect of Astragaloside Ⅳ on Regulation of PI3K/Akt/FoxO1 Signal in Kidney of Type 2 Diabetic Nephropathy Rats
Abstract：Objective:To study the protective effect of astragaloside (AS) Ⅳ on kidney in type 2 diabetic nephropathy rats and its regulation effect on phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O1(FoxO1) signaling, and investigate the mechanism of glycosides against type 2 diabetic nephropathy.Method:After 6 weeks of high-glucose and high-fat diet, rat models of type 2 diabetes were established by intraperitoneal injection of streptozotocin (STZ) (35 mg·kg-1) and randomly divided into model group, AS-Ⅳ (20, 40, 80 mg·kg-1) groups and metformin hydrochloride (positive) group. After 8 weeks of continuous administration, changes in body weight, kidney index, blood glucose, 24-hour urinary protein, urinary microalbumin, urinary creatinine, serum creatinine, and blood urea nitrogen were measured in each group; hematoxylin-eosin (HE) staining was used to observe the pathological changes of renal tissues; Masson trichrome staining was used to observe the collagen expression level. Periodontium hexaammine silver (PASM) staining was used to observe the changes of basement membrane. Immunohistochemistry assay was used to detect phospho-FoxO1(p-FoxO1) protein expression, and Western blot was used to analyze the expression levels of autophagy marker protein PI3K, microtubule-associated protein 1 light chain 3 (LC3)/Ⅱ, B-cell lymphoma-2 (Bcl-2)/adenovirus E1B19 kDa interacting protein 3 (BNIP3), Beclin1, p-Akt, and Akt.Result:As compared with the normal group, the glomerular basement membrane of the model group was thicker; the extracellular matrix was increased; the mesangial was expanded; the collagen was significantly increased; the PI3K/Akt/FoxO1 signal was increased(P<0.01); and the autophagic activity was weakened (P<0.01). As compared with the model group, the phosphorylation of PI3K, Akt, and FoxO1 in renal tissue was significantly inhibited in AS-Ⅳ high and medium dose groups (P<0.05, P<0.01); autophagy was increased; and the expression of BNIP3, LC3 Ⅱ/LC3 I, and Beclin1 was up-regulated (P<0.05, P<0.01).Conclusion:AS-Ⅳ may increase the autophagic activity of renal cells by inhibiting PI3K/Akt/FoxO1 signal, slowing down the development of type 2 diabetic nephropathy.Keywords：diabetic nephropathy;astragaloside Ⅳ;phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O1(FoxO1) signaling;autophagy- 10
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Effect of Lumbricus Peptides on TLR4/NF-
κ B Signaling Pathway in Spontaneous Hypertensive Rat KidneyAbstract：Objective:to observe the effect and mechanism of lumbricus peptides on early renal injury in spontaneous hypertensive rats (SHR) based on Toll-like receptors 4 (TLR4)/nuclear factor-κB(NF-κB) signaling pathway.Method:The 40 SHRs were randomly divided into model group (equal volume of distilled water by intragastric administration), lumbricus peptides low, middle and high dose groups (126, 252, 504 mg·kg-1), and Benazepril group (0.9 mg·kg-1), n=8 in each group. 8 male rats with normal blood pressure at the same age were set as the normal control group, with equal volume of distilled water. After treatment for 60 consecutive days, enzyme-linked immunosorbent assay (ELISA) was used to determine microalbumin (mAlb)and N-acetyl-β-D-glucosaminidase (NAG) content in 24 h urine as well as the level of serum angiotensinⅡ (AngⅡ). Ultrastructural changes of rat kidneys were observed by transmission electron microscope. Western blot was used to detect renal TLR4, NF-κB p65 protein levels. Immunohistochemical method was used to detect renal tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10) expression.Result:As compared with the normal control group, the levels of urine mAlb, NAG and serum Ang Ⅱ were increased in the model group (P<0.05); the expression of TLR4 and NF-κB p65 protein was increased (P<0.05); expression of TNF-α was increased (P<0.05), while IL-10 expression was decreased (P<0.05). Transmission electron microscopy of kidney tissues showed that most of the glomeruli of the model group had podocyte foot process fusion, mesangial cells and mesangial matrix hyperplasia. As compared with the model group, the levels of urine mAlb, NAG, and serum Ang Ⅱ were decreased in the rats in lumbricus peptides groups and benazepril group (P<0.05); the expression of TLR4 and NF-κB p65 protein was decreased (P<0.05); the positive expression of TNF-α in kidney was decreased to different extent (P<0.05), but the expression of IL-10 was increased (P<0.05). Transmission electron microscopy of kidney tissues showed that the damage of kidneys in rats after administration of high-dose lumbricus peptides and benazepril was improved in varying degrees.Conclusion:lumbricus peptides can reduce early renal damage in SHRs, and its mechanism may be achieved by regulating the AngⅡ-TLR4/NF-κB pathway.Keywords：lumbricus peptides;spontaneously hypertensive rat;angiotensin Ⅱ;Toll-like receptors 4(TLR4);nuclear factor-κB(NF-κB)- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Effect of Fengshi Qutong Capsule on Collagen-induced Arthritis of Rats
Abstract：Objective:To observe the intervention effect of Fengshi Qutong capsule on collagen-induced arthritis (CIA) in rats.Method:SD rats were randomly divided into normal group, model group, low, medium and high-dose Fengshi Qutong capsule groups (0.25, 0.5, 1 g·kg-1·d-1), and methotrexate group(0.2 mg·kg-1·d-1). Except for normal group, the other groups were immunized with type Ⅱ collagen and incomplete Freund's adjuvant to establish a CIA model. On the 1st day after the first immunization, the administration group was given intragastric administration, once a day, for 19 days; on the 8th day after the first immunization, the symptoms of joint swelling and malformation of the rats were observed, and the clinical scores and incidence of arthritis were evaluated. On the 19th day, micro-computed tomography and bone metrology were performed, and histopathological examination of inflammatory joints was performed, andsynovial inflammation, vasospasm, cartilage erosion and bone destruction by pathological severity scores, serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), matrix metalloproteinase-3 (MMP-3) and receptor activator of nuclear factor kappa B ligand(RANKL)were detected by enzyme linked immunosorbent assay.Result:Fengshi Qutong capsule could improve the symptoms of inflammatory joint redness, swelling and deformity in CIA rats in a dose-dependent manner. Compared with normal group, clinical score and incidence, joint synovial inflammation, vasospasm, cartilage erosion and pathological score of bone destruction in joint group were significantly increased (P<0.01), bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), trabecularnumber (Tb.N) were significantly decreased (P<0.01), bone surface area/bone volume (BS/BV) and trabecular separation (Tb.Sp) were significantly elevated (P<0.01), and levels of IL-1β, TNF-α, VEGF, MMP-3 and RANKL in serum were increased (P<0.01); compared with model group, clinical scores and incidence, joint synovial inflammation, vasospasm, cartilage erosion and bone destruction of each drug groupwere significantly lower (P<0.05, P<0.01), BMD, BV/TV, Tb.Th, Tb.N were significantly elevated (P<0.05, P<0.01), BS/BV and Tb.Sp were significantly decreased (P<0.05, P<0.01), and levels of serum IL-1β, TNF-α, VEGF, MMP-3 and RANKL were significantly decreased (P<0.05, P<0.01). And the control drug methotrexate had similar effects to the high-dose group.Conclusion:Fengshi Qutong capsule can effectively alleviate the clinical symptoms and conditions of experimental rheumatoid arthritis in rats, reduce the incidence, and relieve the histopathology and imaging severity, while inhibiting the inflammatory cytokines.Keywords：Fengshi Qutong capsule;collagen-induced arthritis;histopathology;radiography;cytokines- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Effect of Bushen Tongluo Prescription on TGF-
β 1/Smads Pathway in Pulmonary Fibrosis RatsAbstract：Objective:To observe the effect of Bushen Tongluo prescription on the pathogenesis of lung fibrosis induced by bleomycin and the transforming growth factor β1(TGF-β1)/Smads pathway protein in rats, and reveal the mechanism of this formula in inhibiting pulmonary fibrosis.Method:Totally 48 male SD rats were randomly divided into five groups: normal group(8 rats), model group(10 rats), high and low-dose Bushen Tongluo group(10 rats)and hydrocortisone sodium succinate group(10 rats). The model of pulmonary fibrosis was made with bleomycin except for normal group.Since day 3 after surgery, 14.2, 7.1 g·kg-1 Bushen Tongluo prescription were given by ig in high and low-dose Bushen Tongluo groups, and 4.58 g·kg-1 hydrocortisone sodium succinate was given by gavage(ig) in normal group and model group.All of the rats were put to death after 28 days.The contents of hydroxyproline (HYP), hyaluronic acid (HA) and laminin (LN) were measured after the death of the rats.Hematoxylin-eosin staining (HE) and Masson tricolor staining were used to observe the pathological changes of lung tissue. Real-time PCR and Western blot were used to observe the changes of mRNA and protein expressions of lung tissues TGF-β1, Smad2, Smad3, Smad7 in each group.Result:Compared with normal group, the level of pulmonary fibrosis was more significant in model group, and the serum HYP, HA and LN were increased obviously(P<0.05, P<0.01). The expressions of TGF-β1, Smad2, Smad3 proteins and mRNA in lung tissues were increased obviously(P<0.05, P<0.01). The expressions of Smad7 protein and mRNA were decreased significantly(P<0.01). Compared with model group, the contents of HYP, HA and LN in high-dose Bushen Tongluo group were decreased obviously(P<0.05, P<0.01), the expressions of lung tissues TGF-β1, Smad2, Smad3 protein and mRNA were decreased obviously(P<0.05), and the expressions of Smad7 protein and mRNA was increased significantly(P<0.01).Conclusion:Bushen Tongluo prescription can effectively improve the pathological process of pulmonary fibrosis, and the mechanism may be related to the regulation of TGF-β1/Smads pathway.Keywords：Bushen Tongluo prescription;pulmonary fibrosis;transformation growth factor;bleomycin;Renshen Gejie San- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Analysis of Pharmacological Effect of Total Tannins from Spatholobi Caulis on Cervical Cancer HeLa Cells by 3D Microfluidic Chip
Abstract：Objective:To study on the chemical constituents of total tannins from Spatholobi Caulis, and to analyze the pharmacodynamics and mechanism of total tannins from Spatholobi Caulis on cervical cancer HeLa cells.Method:UPLC-Q-TOF/MS was used to qualitatively analyze the composition of total tannins from Spatholobi Caulis.The appropriate concentration and time of administration were screened by 3 dimensional(3D) microfluidic chip.Flow cytometry was used to determine the effect of total tannins from Spatholobi Caulis on the cell cycle and apoptosis of cervical cancer HeLa cells and analyzed by FlowJo v10.0.7 and ModFit LT 3.2 software.Enzyme-linked immunosorbent assay(ELISA) was used to determine the changes of vascular endothelial growth factor(VEGF)-A and Caspase-3 factors in cervical cancer HeLa cells supernatant treated with total tannins from Spatholobi Caulis.Result:Total of 15 components in total tannins from Spatholobi Caulis were identified or inferred.The low, medium and high dosages of total tannins from Spatholobi Caulis were 0.5, 1.0, 2.0 g·L-1 and the best time of administration was 36 h. The proportions of early and late apoptosis of cervical cancer HeLa cells increased significantly in the apoptosis analysis after being treated by total tannins from Spatholobi Caulis.The DNA synthesis early phase(G0/G1 phase) of cervical cancer HeLa cells significantly increased, and the DNA synthesis phase(S phase) and the DNA synthesis late phase(G2/M phase) reduced.After being treated with total tannins from Spatholobi Caulis, the expression of VEGF-A in cervical cancer HeLa cells supernatant was significantly decreased and the expression of Caspase-3 was significantly increased.Conclusion:Spatholobi Caulis is rich in tannins, which can significantly inhibit the proliferation of cervical cancer HeLa cells and promote its apoptosis.This paper can provide the basis for further research of total tannins from Spatholobi Caulis.Keywords：Spatholobi Caulis;total tannins;3D microfluidic chip;cervical cancer HeLa cells;cell apoptosis;cell cycle;enzyme-linked immunosorbent assay- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Molecular Mechanism of Banxia Baizhu Tianma Tang in Treating Hypertension Based on Integrated Pharmacological Platform
Abstract：Objective:To explore the molecular mechanism of Banxia Baizhu Tianma Tang in treating hypertension.Method:Based on an internet-based computation platform for integrated pharmacology of traditional Chinese medicine(TCM), TCM prescription database, TCM database, TCM component database and disease/symptoms target database, information on the chemical compositions contained in TCM was retrieved, an interaction network between potential targets and disease targets of Banxia Baizhu Tianma Tang was built, then core target was enriched and calculated, gene function and pathway analysis was carried out, the multi-dimensional relationship network of "Chinese herbs-ingredients-critical targets-key pathways" of Banxia Baizhu Tianma Tang was further constructed.Result:A total of 90 active ingredients in Banxia Baizhu Tianma Tang were obtained, including alkaloids, nucleosides, flavonoids, saponins, organic acids and other ingredients; they involved 287 core targets, including 13 direct targets, such as adenylate cyclase, G protein coupled with β1 receptor, glucose kinase, etc; they also involved nervous system, endocrine system, circulatory system, estrogen signaling pathway, chemokine signaling pathway and other related biological processes and signaling pathways.Conclusion:Banxia Baizhu Tianma Tang can regulate neurotransmitter concentration and activity abnormalities, improve the protective effect of vascular endothelial cells by improving insulin resistance, regulating the production of inflammatory factors, and inhibiting inflammatory reactions, thereby exerting pharmacological effects on the treatment of hypertension.This study can provide a scientific basis for comprehensive interpretation of mechanism of Banxia Baizhu Tianma Tang.Keywords：Banxia Baizhu Tianma Tang;hypertension;integrated pharmacology;mechanism;database;glucose kinase;nervous system- 10
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09
Pharmacology
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Dynamic Changes of Biomarker Levels in Early Stage of Acetaminophen-induced Liver Injury
Abstract：Objective:To determine whether glutathione dehydrogenase (GLDH), purine nucleotide phosphorylase (PNP), α-glutathione-S-transferase (α-GST), and arginase 1 (Arg1) can be used as the early biomarkers of drug-induced liver injury by comparing the changes of traditional biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), total bilirubin (TBIL) and potential biomarkers GLDH, PNP, α-GST and Arg1 in acetaminophen (APAP)-induced liver injury model rats.Method:The 48 rats were randomly divided into two groups: blank group and model group. 24 rats in each group, half male and half female. The model group received 1 250 mg·kg-1 APAP solution by intragastric administration to establish the drug-induced liver injury. 6 rats (half male and half female) were randomly selected from each group at 3, 6, 12 and 24 h after APAP was given to the model group, to detect the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST, Arg1 in serum and levels of GLDH, PNP, α-GST, Arg1 in liver tissue homogenate at each time point Histopathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining.Result:As compared with the blank group, the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST and Arg1 in serum and liver homogenates were significantly increased in model group(P<0.05, P<0.01), indicating that the APAP-induced liver injury model was successfully replicated. GLDH, PNP, α-GST and Arg1 levels in serum and liver tissues of rats in the model group were increased earlier and more significantly than ALT and AST levels.Conclusion:GLDH, PNP, α-GST and Arg1 can be used as biomarkers for early detection of drug-induced liver injury.Keywords：acetaminophen;drug-induced liver injury;early biomarker;change law- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Changes of CCl4-induced of Liver Injury in Rats for 24 Hours
Abstract：Objective:To replicate the animal model of liver injury in rats by using carbon tetrachloride (CCl4), investigate the dynamic changes of early biomarkers of liver injury, namely glutamate dehydrogenase (GLDH), purine nucleotide phosphorylase(PNP), α-dynamic changes of glutathione-S-transferase (α-GST) and arginase 1(Arg1), and provide experimental evidence for early detection of acute liver injury.Method:Forty-eight Wistar rats were randomly divided into a blank group and a model group. The model group was intraperitoneally injected with 10 mL·kg-1 10% CCl4 olive oil solution, fasting but except water. Animals were sacrificed at 3, 6, 12, and 24 h. The serum liver function alanine aminotransferase(ALT), aspartate aminotransferase (AST), bilirubin (TBIL), alkaline phosphatase (ALP) levels, α-GST, Arg1, GLDH, PNP levels, and liver homogenate superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) levels were then detected.Result:As compared with blank group, the levels of ALT, AST, TBIL, α-GST, Arg1, GLDH, PNP and MDA were increased significantly 3 h after administration, and SOD was decreased significantly(P<0.01). After 6, 12 h, the levels of ALT, AST, α-GST, ARG-, GLDH, TBIL, ALP and MDA were increased significantly, while GSH and SOD were decreased significantly (P<0.05, P<0.01). After 24 h, the levels of ALT, AST, α-GST, Arg1, TBIL, ALP and MDA were significantly increased, while GSH and SOD were significantly decreased (P<0.01).Conclusion:α-GST, Arg1, GLDH and PNP have better sensitivity than traditional liver function test indicators, and can be used for early detection of liver injury induced by CCl4 in rats.Keywords：liver injury;carbon tetrachloride(CCl4);early biomarkers;change law- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Changes of Serum Biomarkers levels in Early Stage of Alcohol-induced Liver Injury in Rats
Abstract：Objective:To investigate the dynamic changes of the biomarkers of alcoholic liver injury, including glutamate dehydrogenase(GLDH), α-glutathione-S-transferase(α-GST), purine nucleotide phosphorylase(PNP), and arginine enzyme 1(Arg1), and clarify whether these indexes can be used as early diagnostic biomarkers for alcoholic liver injury.Method:48 Wistar rats were randomly divided into a blank group and a model group, 24 rats in each group, half male and half female. After fasting but except water for 7 h, 50% ethanol/10 mL·kg-1 was given to the model group by intragastric administration and the same volume of normal saline was administered to the blank group. After 1 h, 50% ethanol was again given for once by intragastric administration according to the previous dosage. In the blank group, the same volume of normal saline was administered. After modeling and administration for 6 d, acute alcoholic liver injury model was established. 3 h after the last intragastric administration of alcohol at day 2, 3, 4, 6, six rats (half male and half female) in each group were randomly selected. All the animals were sacrificed to determine the aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), bilirubin(TBIL), GLDH, α-GST, PNP, and Arg1 levels.Result:As compared with the blank group, the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST and Arg1 in the model group were significantly different (P<0.01), indicating that the alcoholic liver injury model was successfully established. In the model group, GLDH, PNP, α-GST and Arg1 levels were increased earlier and more significantly than ALT and AST levels.Conclusion:GLDH, PNP, α-GST and Arg1 can be used as biomarkers for early detection of alcoholic liver injury.Keywords：acute liver injury;alcohol;early biomarkers;change law- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09
Topic on Changes of Biomarkers in Animal Models of Early Liver Injury
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Clinical Observation of Jiawei Xiaoyaosan in Treating Liver Depression and Spleen Deficiency Type 2 Diabetes with Emotional Disorder
Abstract：Objective:To observe the clinical efficacy of Jiawei Xiaoyaosan for patients with anxiety and depression in type 2 diabetes with liver depression and spleen deficiency.Method:The 76 eligible patients with anxiety and depression in type 2 diabetes with liver depression and spleen deficiency were randomly divided into two groups: control group (38 cases) and treatment group (38 cases). In control group, the basic medicines metformin sustained-release tablets combined with deanxit were given; based on the treatment in control group, the patients in treatment additionally received Jiawei Xiaoyaosan. The changes of fasting plasma glucose (FPG), 2 hours postprandial blood glucose (2 hPG), haemoglobin A1c (HbA1c), fasting insulin (FINS) and serum insulin levels 30 minutes after glucose intake (30 min INS), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and so on were observed and compared.Result:As compared with those before treatment, the levels of FPG, 2 hPG and HbA1c were decreased significantly (P<0.05), fasting serum insulin levels were significantly decreased (P<0.01), 30 min INS levels were increased (P<0.05); HAMD and HAMA scores were significantly decreased (P<0.05). After treatment, the levels of FPG, 2 hPG and HbA1c in the treatment group were significantly lower than those in control group (P<0.01), and the FINS level in treatment group was lower (P<0.05) while 30 min INS level was higher than those in control group (P<0.05); in addition, the HAMD and HAMA scores in the treatment group were significantly lower than those in control group (P<0.01), but there was no significant difference in adverse reactions between two groups.Conclusion:Jiawei Xiaoyaosan combined with basic medication can significantly reduce depression and anxiety in patients with type 2 diabetes mellitus of liver depression and spleen deficiency, reduce blood glucose, glycosylated hemoglobin, decrease fasting insulin and increase 30 min INS level. The effect may be related to the improvement of anxiety, depression and other adverse emotions in these patients.Keywords：Jiawei Xiaoyaosan;liver depression and spleen deficiency;type 2 diabetes;dysthymic disorder- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Clinical Efficacy of Tongqiao Huoxuetang in Treating Blood Stasis Type Vascular Cognitive Impairment
Abstract：Objective:This study aims to observe the clinical efficacy of Tongqiao Huoxuetang in treating blood stasis resistance type vascular cognitive impairment, and explore its mechanism of action.Method:A total of 60 patients who met the inclusion standards and were diagnosed as blood stasis resistance type vascular cognitive impairment were randomly divided into treatment group and control group, 30 patients in each group. Donepezil hydrochloride was administered orally in control group based on internal medicine treatment at an initial dose of 5 mg/day, changed to 10 mg/day 4 weeks later. Patients in treatment group additionally received Tongqiao Huoxuetang based on donepezil hydrochloride. Both groups were treated for 3 months. Changes of symptoms were assessed by syndrome scores; cognitive function was assessed by the mini-mental scale (MMSE); daily living ability was assessed by the activity of daily living scale (ADL), and changes of local blood perfusion (CBF value) was assessed by brain magnetic resonance perfusion imaging arterial spin labeling (MRI-ASL). Changes of homocysteine levels in plasma were measured by using an automated biochemical analyzer.Result:① The values of traditional Chinese medicine(TCM) syndrome scores (SDSVD) were significantly improved in both groups after treatment, and the improvement was more obvious than that of control group (P<0.05). ② The cognitive ability and daily living ability of the patients were significantly improved; the MMSE scores and ADL scores were improved significantly in both groups after treatment (P<0.01), and improvement in treatment group was more obvious than that of control group (P<0.05). ③The CBF value in treatment group was significantly higher after treatment (P< 0.05), and also higher than that in control group (P <0.01). ④ Homocysteine level in plasma of treatment group was significantly lower than that of control group (P <0.05).Conclusion:The combination of Tongqiao Huoxuetang combined with donepezil hydrochloride can effectively improve the cognitive ability and daily living ability of the patients with vascular dementia, improve the cerebral blood flow perfusion and decrease the level of homocysteine, so it is worth popularizing in clinical practice.Keywords：vascular cognitive impairment;Tongqiao Huoxuetang;magnetic resonance perfusion imaging;homocysteine- 10
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Clinical Effect of Jiawei Xijiao Dihuang Tang on Henoch-Schonlein Purpura Nephritis of Children with Blood Heat and Stasis Syndrome
Abstract：Objective:To observe the clinical effect of Jiawei Xijiao Dihuang Tang on Henoch-schonlein purpura nephritis of children with blood heat and stasis syndrome and the inflammatory factors and coagulation function.Method:One hundred and twenty-two patients were divided into control group (60 cases) and observation group (62 cases) by random number table. Patients in control group got prednisolone acetate tablets every day, 1.5-2 mg·kg-1·d-1, after 4 weeks, of the treatment, and the 4 weeks dosage decreased progressively. Patients in control group also got dipyridamole tablets, 3-5 mg·kg-1·d-1, and compound rutin tablets, 1 tablet/day, 3 times/days. In addition to the therapy of control group, patients in observation group were also given Jiawei Xijiao Dihuang Tang, 1 dose/day. And one course of treatment was 12 weeks. Before and after treatment, blood heat and stasis syndrome were graded. And levels of urinary β2 microglobulin (β2-MG), 24-hour urine protein quantitative (24 h UmAlb), microalbuminuria (mAlb), cystatin C (CysC), platelet count (PLT), plasma prothrombin time (PLT), plasma prothrombin time (PT), activated partial thromboplastin time (APTT), interleukins-2 (IL-2), IL-4, IL-10, tumor necrosis factor-α (TNF-α), von willebrand factor (vWF), platelet activating factor (PAF), thrombomodulin (TM), plasma fibrinogen (FIB), urine RBC and urine protein (PRO) were detected.Result:The total clinical effect in observation group was 95.16%, which was higher than 81.54% in control group (χ2=5.466, P<0.05). And the total symptoms of traditional Chinese medicine(TCM)was 96.77%, which was higher than 75% in control groups (χ2=12.052, P<0.01). After treatment, levels of β2-MG, 24 h UmAlb, mAlb and CysC were higher than those in control groups (P<0.01). And PT in both groups prolonged, particularly in observation group (P<0.05). Level of FIB in observation group was lower than that in control groups (P<0.05). And levels of IL-4, IL-10, TNF-α and vWF, PAF and TM were lower than those in control groups, but level of IL-2 was higher than that in control groups (P<0.01).Conclusion:In addition to the hormone therapy, Jiawei Xijiao Dihuang Tang can protect renal function, relieve symptoms of proteinuria and hematuria, with the effects of resisting inflammation and alleviating coagulation function.Keywords：henoch-schonlein purpura nephritis;blood heat and stasis syndrome;Xijiao Dihuang Tang;anti-inflammation;coagulation function;renal function- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Effect of Modified Simotang on Adult Functional Constipation and Intestinal Neurotransmitter
Abstract：Objective:To observe the efficacy of modified Simotang in treatment of adult functional constipation (Qi-stagnancy constipation), and investigate its effects on serum levels of intestinal neurotransmitter nitric oxide synthase (nNOS), nitric oxide (NO), and vasoactive intestinal peptide (VIP), as well as superoxide dismutase (SOD), malonaldehyde (MDA), and glutathione (GSH) levels.Method:One hundred and ten patients with functional constipation were selected and randomly divided into control group (55 cases) and treatment group (55 cases) by referring to random number table. The patients in control group were given with routine therapy, Domperidone tablet (1 tablet/time, tid), and Phenolphthalein tablets (100 mg/time, bid). The patients in treatment group were treated with modified Simotang, 1 dose/day. Both groups were treated for 4 weeks. Then the scores of main clinical symptoms of functional constipation, scores of Qi-stagnancy constipation and clinical efficacy were compared between two groups. Constipation recurrence rate was compared between two groups after stopping medicine. Serum levels of intestinal neurotransmitters nNOS, NO and VIP as well as SOD, MDA, GSH levels were detected in both groups.Result:After treatment, scores for main clinical symptoms (difficult defecation, abdominal distension, defecation time, number of defecation times) and Bristol scores in treatment group were obviously lower than those in control group (P<0.01). Scores for symptoms of Qi-stagnancy constipation (ungratifying defecation, abdominal distension, bowel ringing, frequent flatus, chest and flank tightness) in treatment group were obviously lower than those in control group after treatment (P<0.01). Total clinical efficacy in treatment group 98.04% was superior to that in control group 84.62% ( P<0.05). Constipation recurrence rate was 3.92% and 8.16% in treatment group after 4 and 8 weeks of medication stopping, obviously lower than those in control group 18.18% and 27.78% (P<0.05). After treatment, serum levels of intestinal neurotransmitters nNOS, NO, VIP in treatment group were remarkably lower than those in control group (P<0.01). After treatment, serum levels of SOD and GSH in treatment group were higher while MDA level was lower than those in control group (P<0.01).Conclusion:Based on routine therapy, modified Simotang in treatment of adult functional constipation (Qi-stagnancy constipation) can improve clinical symptoms and syndrome symptoms, increase the clinical efficacy, decrease recurrence rate, and regulate levels of intestinal neurotransmitters nNOS, NO and VIP as well as SOD, MDA, GSH levels.Keywords：Simotang;functional constipation;Qi-stagnancy constipation;intestinal neurotransmitter- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09
Clinic
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Isolation and Identification of Antioxidant Activity Constituents from Elephantopus scaber
Abstract：Objective:To study the chemical constituents of 95% ethanol extract of the whole plant of Elephantopus scaber and investigate its antioxidant activity.Method:The chemical constituents were isolated and purified by silica gel column chromatography, Sephadex LH-20 column chromatography, ODS column chromatography, semi-preparative high performance liquid chromatography (HPLC) and recrystallization methods, while their structures were identified on the basis of nuclear magnetic resonance (NMR), mass spectrometry and comparison of their spectral data with those reported in the literature.Result:Fourteen compounds were isolated and their structures were identified as: (E)-3-(3, 4-dihydroxybenzylidene)-5-(3, 4-dihydroxyphenyl)-2(3H)-furanone (1), esculetin (2), dihydrosyringenin (3), (+ )-isololiolide (4), caffic acid (5), luteolin-7-O-β-D-glucuronide (6), luteolin-7-O-β-D-glucuronide methyl ester (7), chlorogenic acid methyl ester (8), blumenol A (9), (6R, 9R)-3-oxo-α-ionol-β-D-glucopyranoside (10), byzantionoside B (11), 3, 5-O-dicaffeoyl quinic acid methyl ester (12), 3, 4-O-dicaffeoyl quinic acid methyl ester (13) and 4, 5-O-dicaffeoyl quinic acid methyl ester (14).Conclusion:Compounds 1-4 and 8-10 were isolated from the genus Elephantopus for the first time. Compound 11 was isolated from E. scaber for the first time. The DPPH radical and ABTS+ radical scavenging experiments on twelve of these compounds showed that compounds 1, 2, 5, 6, 12 and 13 had significant antioxidant activity.Keywords：Elephantopus scaber;95% ethanol extract;antioxidant activity;esculetin;dihydrosyringenin- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Chemical Constituents of Lipid-soluble Parts of Tinospora sinensis
Abstract：Objective:To isolate the chemical constituents from lipid-soluble parts of Tibetan Tinospora sinensis and identify the structure of the monomer compounds.Method:Eighty kg of dried rhizomes of T. sinensis were soaked by 80% ethanol (5 times of the dose of crude drug) for 1 hour, boiled under reflux for 1 hour, then and filtered. The above steps were repeated. The two extracts were combined, and the solvent was recovered to obtain a total extract. The obtained extract was extracted with a conventional solvent, and the solution was recovered to obtain petroleum ether extract, methylene chloride extract, ethyl acetate extract, n-butanol extract and water extract. Methylene chloride extract was isolated and purified by silicagel column chromatography, semi-preparative liquid chromatography and SephadexLH-20 chromatography; the chemical structure was identified on the basis of ESI-MS, nuclear magnetic resonance (1H-NMR and 13C-NMR) spectroscopy data and literatures.Result:Fifteen compounds were isolated and identified respectively as n-dodecanol (1), n-hexacosanol (2), palmitic acid (3), dibutyl phthalate (4), vanillic acid (5), vanillin (6), apocynin (7), tinocordifolioside (8), medioresinol (9), isolariciresinol (10), aurantiamide (11), aurantiamide acetate (12), berberine (13), daucosterol (14), β-sitosterol (15).Conclusion:Except for 3, 4, 6, 14, 15, the other 10 compounds were isolated from the plant for the first time.Keywords：Tinospora sinensis;rhizome;liposoluble components;n-dodecanol;n-hexacosanol- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Phenolic Components from Roots of Psidium guajava
Abstract：Objective:The different parts of Psidium guajava(Myrrhinaceae) have different bioactivities. There are intensive studies for chemical constituents of its leaves and fruits at present. However, there are a few studies for the roots. Therefore, we systematically investigated the chemical constituents of phenolic acids in roots of P. guajava.Method:The chemical constituents were isolated and purified by various column chromatography methods and semi-preparative HPLC. The isolated compounds were identified by physicochemical properties and spectral analysis.Result:Sixteen phenolic components were isolated from the ethanol extract and identified as 3, 3′, 4′-tri-O-methylellagic acid(1), 3, 3′, 4-tri-O-methylellagic acid-4′-O-β-D-glucopyranoside(2), 3-O-methylellagic acid-4′-O-α-L-rhamnopyranoside(3), 3′-O-methyl-3, 4-O, O-metheneellagic acid-4′-O-β-D-glucopyranoside(4), gallic acid(5), methyl gallate(6), ethyl gallate(7), 3, 4, 5-trimethoxypheny-1-β-D-glucopyranoside(8), 3, 5-dimethoxy-4-hydroxy-benzoic acid-7-O-β-D-glucoside(9), 1-hydroxy-3, 4, 5-trimethoxyphenyl-1-O-[6′-O-(4″-carboxy-1″, 3″, 5″-trihydroxy)phenyl]-β-D-glucopyranoside(10), vanillic acid(11), protocatechuic acid(12), secoisolariciresinol 9-O-β-D-glucopyranoside(13), phloretin 4′-O-β-D-glucopyranoside(14), cinchonain Ib(15) and epicatechin(16).Conclusion:Compounds 3,4,6,8-10,13-15 were isolated from this plant for the first time.Keywords：Psidium guajava;root;phenolic acid;alcohol extract- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Chemical Constituents from Sprout of Ziziphi jujuba var. spinosa
Abstract：Objective:To investigate the chemical constituents from sprout of Ziziphi jujuba var. spinosa, and explore the effect of germination on the activity of Z. jujuba var. spinosa seed from the perspective of material basis.Method:The dry sprout of Z. jujuba var. spinosa was crushed and extracted with petroleum ether to remove oils and fats, then the residues were dried and received reflux extraction with methanol. The solvent was decompressed and recovered to obtain methanol fractions. The fractions were dissolved, isolated and purified by column chromatography technologies such as silica gel, RP C18 and Sephadex LH-20, and the structures of the compounds were identified by nuclear magnetic resonance (NMR), mass spectrometry (MS) and reference liteature.Result:The 13 compounds were isolated from the sprout of Z. jujuba var. spinosa and identified as jujuboside B (1), jujuboside D (2), jujuboside A (3), betulinic acid (4), betulin (5), lupeol (6), alphitolic acid (7), ceanothic acid (8), oleanolic acid (9), ursolic acid (10), magnoflorine (11), nuciferine (12) and swertisin (13).Conclusion:All the above compounds were isolated from the sprout of of Z. jujuba var. spinosa for the first time. The study showed that the chemical constituents from the sprout were quite similar with those from the seeds of Z. jujuba var. spinosa, mainly including triterpenoids and saponins, flavonoids, alkaloid, etc.Overall, the results described in this study could provide certain chemical basis for further resources exploitation and utilization of the sprout of Z. jujuba var. spinosa.Keywords：sprout of Ziziphi jujuba var. spinosa;triterpenoids and saponins;chemical constituents- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Isolation and Identification of Chemical Constituents from Goodyera schlechtendaliana
Abstract：Objective:To isolate and purify the chemical constituents from Goodyera schlechtendaliana, and lay a foundation for further research on the effective materials of the plant.Method:The dried grass of G. schlechtendaliana(10 kg)was heated by 95% EtOH for reflux extraction for 4 times at 85 ℃. The extract liquids were combined, decompressed and concentrated to obtain the crude extract. The crude extract was then suspended in distilled water and extracted with petroleum ether, EtOAc and n-BuOH in turn to obtain corresponding fractions. Silica gel, Sephadex LH-20, ODS and semi-preparation high performance liquid chromatography (HPLC) were used for the separation and purification of EtOAc and n-BuOH fractions. The structures of compounds obtained were identified by 1H-NMR, 13C-NMR, MS, physicochemical properties and reference literature.Result:Ten compounds were isolated and identified as 2, 5-dihydroxy-4-methoxy-9, 10-dihydroxyphenanthrene (1), 1, 3, 5-trimethoxybenzene (2), protocatechuic acid (3), p-hydroxybenzaldehyde (4), p-hydroxybenzoic acid (5), quercetin (6), vanillin(7), daucosterol (8), adenine (9) and adenosine (10).Conclusion:Compounds 1-10 were obtained from the genus of Goodyera for the first time.Keywords：Goodyera schlechtendaliana;chemical constituent;isolation and purification;structure identification- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
HPLC Fingerprint of Different Polarity Fractions of Gardeniae Fructus with Different Fruit Shapes
Abstract：Objective:To investigate and compare the fingerprints of different polarity fractions (petroleumether, chloroform, ethyl acetate, n-butanol, water) of fresh Gardeniae Fructus with different fruit shapes, and further understand the content difference and distribution of its chemical composition.Method:Gardeniae Fructus was reflux extracted by water in order to obtain the water extract; water extract 0.1 g and dissolved with 50 mL water, then it was extracted by petroleum ether, chloroform, ethyl acetate and n-butanol in turn in order to obtain the different extraction phases and the water phase. Each phase was condensed to extractum. Finally, the samples were analyzed by high performance liquid chromatography (HPLC) fingerprints and the similarity evaluation software was used for data analysis.Result:Fingerprint of chloroform fraction of water extract in gardenia from different habitats can be used to distinguish Gardeniae Fructus from Fujian, Henan and Jiangxi. The differences between the water extract of Gardeniae Fructus from Fujian and those of Henan and Jiangxi were mainly manifested in the petroleum ether fraction, and the fat-soluble components of Gardeniae Fructus were more than those of Henan and Jiangxi. The differences between the water extract of Gardeniae Fructus from Henan and those of Fujian and Jiangxi were mainly manifested in the ethyl acetate fraction, and the content of iridoid glycosides was significantly higher than that in Fujian and Henan. The differences between the water extract of gardenia from Jiangxi and those of Fujian and Henan were mainly manifested in the n-butanol fraction, organic acid peak C1 not detected. The fingerprint of chloroform fraction of water extract in Gardeniae Fructus can be used to distinguish Gardeniae Fructus of six ribs and Gardeniae Fructus of seven ribs from Fujian and Henan, and the contents of all components of Gardeniae Fructus of seven ribs were more than those in Gardeniae Fructus of six ribs. The fingerprint of petroleum ether fraction of water extract in Gardeniae Fructus can be used to distinguish Gardeniae Fructus of six ribs and Gardeniae Fructus of seven ribs from Jiangxi. The Z3 peak of Gardeniae Fructus of six ribs from Henan was obviously higher than that of Gardeniae Fructus of seven ribs. The contents of all components on chloroform and ethyl acetate fractions of water extract in Gardeniae Fructus of seven ribs were significantly higher than those of Gardeniae Fructus of six ribs.Conclusion:There are significant differences on chemical constituents and content among Gardeniae Fructus from Fujian, Henan and Jiangxi. The main difference of fingerprint between Gardeniae Fructus of six ribs and Gardeniae Fructus of seven ribs is the peak height.Keywords：Gardeniae Fructus;fruit shape;fresh fruit;polarity fractions;fingerprint;HPLC- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Analysis of Chemical Constituents in Oroxyli Semen by UPLC-Q-TOF-MS
Abstract：Objective:Flavonoids, as the major constituents in Oroxyli Semen, had a variety of pharmacological effects against inflammation, infections, and oxidation. In this study, an ultra-high performance liquid chromatography (UPLC-Q-TOF-MS) method was established to analyze and identify the various flavonoids in Oroxyli Semen.Method:The separation was performed on an Kinetex-XB C18 column(2.1 mm × 50 mm, 1.7 μm)with gradient elution, which was carried out with 0.1%formic acid acetonitrile as mobile phase. The flow rate was 0.25 mL·min-1, and the injection volume was 3 μL. Electrospray ionization source was in the negative ion mode. Target and non-target screenings were carried out by Peakview 2.2 and Masterview 1.0 software. Then the identification of target compounds were completed based on accurate mass, isotopic abundance ratio and MS/MS fragment, and the non-target compounds were determined according to literature reports and MS cleavage mechanism.Result:According to the high resolution MS spectra data, fragmentation ion information and retention time, 36 peaks of Oroxyli Semen were identified, including 10 flavonoids and 26 flavonoid glycosides according to literature reports and MS cleavage mechanism.Conclusion:The study comprehensively analyzes the chemical composition of Oroxyli Semen, which is significant to study of the chemical constituents, quality control and material basis of Oroxyli Semen.Keywords：Oroxyli Semen;UPLC-Q-TOF-MS;chemical component;flavonoids- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
In Vitro Antitumor Bioactivity and GC-MS Analysis of Petroleum Ether Fraction of Boehmeria nivea Root
Abstract：Objective:To define the anti-gastric cancer activity in vitro of petroleum ether fraction of Boehmeria nivea root and reveal the material basis of its efficacy, so as to lay the foundation for the development and utilization of B. nivea root.Method:Methyl thiazolyl tetraolium(MTT) method was used to evaluate the inhibitory rate and time-dose relationship of petroleum ether fraction of B. nivea root with different doses and delivery times on human gastric cancer HGC-27 cells. Flow cytometry was used to detect the change of cell apoptosis and cell cycle after petroleum ether fraction of B. nivea root acted on human gastric cancer HGC-27 cells. GC-MS was used to detect the components of petroleum ether fraction of B. nivea root.Result:Experiment data showed significant cell proliferation inhibition in an obvious time-dose-effect manner, with statistically significant differences (P<0.05), after 24, 48, 72 h of incubation of human gastric cancer HGC-27 cells with different concentrations of petroleum ether fraction of B. nivea root. The effect of petroleum ether fraction of B. nivea root on human gastric cancer HGC-27 cells could induce apoptosis, which affects the normal changes of cell cycle. The percentage of cells was decreased significantly in G0/G1 phase, and that in S phase was significantly increased. GC-MS was used to identify 26 chemical constituents in petroleum ether of B. nivea root, including sitosterol and stigmasterol.Conclusion:Petroleum ether fraction of B. nivea root is the active anti-gastric cancer part, and its main effective component is sterol compounds. This lays the foundation for the rational application of B. nivea root in clinic and the further research in tis anti-tumor effect.Keywords：Boehmeria nivea root;human gastric cancer cell line HGC-27;cell cycle;apoptosis;GC-MS- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09
Quality Evaluation
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Application Status and Research Progress of External Traditional Chinese Medicine Ointment for Rheumatism Treatment
Abstract：Due to the definite curative effect, stable drug properties and low incidence of adverse reactions, the external traditional Chinese medicine(TCM) ointment for rheumatism treatment has attracted more and more attention from scholars at home and abroad.Based on the external TCM ointment for the treatment of rheumatism approved by China Food and Drug Administration(CFDA), this paper would comb and analyze their dosage forms, varieties, specifications, etc.On the other hand, this article summarizes the application of the new formulation technology, prescription research, study on the forming process, pharmacodynamics and safety research, etc.The problems existing in this area were pointed out, such as lack of new preparations; less research on the penetration material basis, the penetration enhancing mechanism, and the penetration enhancing law; the selection of detection indicators of quality control standards is not comprehensive enough; qualitative and quantitative studies of pharmacokinetics are relatively scarce and so on.Meanwhile, proper measures and suggestions are put forward.Not only the formulation classification and specification description of external TCM ointment should be standardized, but also new dosage forms such as intelligentized, controlled release and targeted preparations of Chinese medicine should be actively introduced; the study of transdermal activity of transdermal enhancer itself should be strengthened, and investigating the correlation between the transdermal absorption of the agent itself and promoting transdermal absorption; the biological effect index or indicators that combine chemical and biological effects should be used, and learning from the latest research achievements of multidimensional spectroscopy of Chinese herbal medicine, thereby establishing scientific detection indicators and quality control methods that conform to modern transdermal concept.Keywords：external traditional Chinese medicine ointment;rheumatism;application status;pharmacodynamics;forming process;transdermal behavior;safety- 10
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Explore Regulation Mechanism of "Spleen Qi to Dispersing Essence" on Blood Glucose Homeostasis from Microcirculation of Pancreatic Islet
Abstract：Reducing glycemic excursion is of great importance to the successful practice for diabetes intervention and complication prevention. This is also an advantage of traditional Chinese medicine (TCM) in the treatment of diabetes. More and more studies have shown that the dysfunction of islet microcirculation is the key pathological link for glycemic excursion caused by decrease of islet function. The over-activation of local renin-angiotensin system (RAS) in islet microcirculation is a key ring to the islet decompensation, intimately related to the functionality of islet endocrine cells, and has gradually become the focus in the study of islet functionality. In TCM, it is believed that glycemic excursion in diabetes mellitus is closely related to the incapability of "spleen Qi to dispersing essence" . If spleen fails to disperse essence, the essence will be accumulated in the body and become harmful stuffs. The stuffs further break the blood glucose homeostasis, acting as the key pathogenesis of diabetes. By supplementing the "spleen" Qi and promoting the dispersion of nutrient substance (hormone) in "pancreas" , the balance between sugar-regulated hormones can be restored and therefore glycemic excursion can be reduced. However, the regulation mechanism of "spleen Qi to dispersing essence" on glycemic excursion remains unclear at present. Based on the previous clinical and scientific work, the following ideas were proposed by the authors: the effects of "spleen Qi to dispersing essence" on the improvement of islet function and the regulation of glycemic excursion may be achieved by promoting islet microcirculation, and its mechanism may be related to inhibiting the activation status of local RAS in islet microcirculation. It is important to note that the mutual antagonistic relationship between the signal pathways of RAS in islet microcirculation is similar to the antagonistic relationship between "spleen Qi to dispersing essence" and spermatozoa in TCM. Thus, the mechanism of "spleen Qi to dispersing essence" on the regulation mechanism of blood glucose fluctuations needs to be further explored from the perspective of the overall regulation of RAS in islet microcirculation, so as to reveal the scientific connotation of TCM on regulating the body's environmental homeostasis and reducing glycemic excursion in diabetic patients.Keywords：diabetes mellitus;glycemic excursion;spleen Qi to dispersing essence;islet microcirculation- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Summary and Review of Animal Models for Chronic Atrophic Gastritis and Precancerous Lesions of Gastric Cancer
Abstract：Gastric cancer is a disease with high morbidity and mortality in the world, and also obtains attention in the global medicine. The occurrence of gastric cancer is a multi-stage and multi-factor process. A large number of epidemiological, pathological and clinical evidences have confirmed that the risk of gastric cancer in patients with chronic atrophic gastritis (CAG) is significantly correlated with the mortality of gastric cancer. Gastric mucosal atrophy, intestinal metaplasia (especially incomplete colonic metaplasia) and dysplasia are the main stages of precancerous lesions of precancerous lesions of gastric cancer (PLGC). Monitoring the condition of CAG patients, especially those with intestinal metaplasia and dysplasia, is of great significance for the discovery of early gastric cancer. CAG and PLGC are great significance in the pathological stage of gastric carcinogenesis. In recent years, more and more in-depth clinical and experimental studies have been carried out in this direction. So far, animal experiment is the main research way for CAG and PLGC disease, so it is very important to explore the modeling method. Choosing a stable and reliable model is the primary factor to study animal experiment. In view of the relationship between two diseases, this paper will summarize the methods of establishing animal models for CAG and PLGC in recent years, generally including chemical drug mutagenesis, physical stimulation, immune modeling, Helicobacter pylori infection replication and surgical modeling. Examples would be given for the application of various methods in the previous experiments, and the author would make a brief comment on the merits and demerits of these methods, which have been explored and successfully made by the author. This study would provide certain reference for the establishment and application of animal models in further CAG and PLGC experiments.Keywords：chronic atrophic gastritis (CAG);precancerous lesions of gastric cancer (PLGC);animal model;gastric cancer- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09 -
Treatment of Renal Proteinuria by Traditional Chinese Medicine and Its Mechanism
Abstract：Chronic kidney disease (CKD) refers to abnormal renal structure and function for more than 3 months, and is characterized by abnormal urine, blood and kidney structure. As an important clinical manifestation of CKD, proteinuria is closely related to glomerular damage. It is not only a pathological manifestation of CKD, but also an important pathological factor to accelerate the development of CKD. After thousands of years of development, traditional Chinese medicine (TCM) has a systematic theoretical foundation and rich clinical experience in the treatment of CKD. By referring to the treatment principles and methods of "leakage of vital essence" , "low back pain" , "asthenia" , "blood urine" and "edema" in TCM, the general treatment principle of proteinuria is to coordinate the body Yin and Yang and restore the balance of Yin and Yang. Specific methods include removing blood stasis, sweating, urinating, invigorating the spleen and strengthening the kidney, smoothing liver and activating collaterals, and removing dampness and detoxification. Both ancient and modern physicians have established effective prescriptions according to the treatment principles and methods. Modern studies have showed that the mechanism of TCM to reduce proteinuria is mainly to improve the pathological manifestations of large area fusion of podocyte processes and complete disappearance of poddout, up-regulate the expression of nephrin and podocin, regulate immune, alleviate systemic inflammation, and improve the serum superoxide dismutase(SOD)level and the ability of the body to remove free radicals. The method and mechanism of treating renal proteinuria are discussed from three aspects: classical prescriptions, empirical prescriptions and the Chinese patent medicine. It provides a theoretical reference for the clinical treatment of chronic kidney disease, reducing the excretion of proteinuria and improving the clinical symptoms of the patients.Keywords：chronic kidney disease(CKD);proteinuria;therapeutic method;classical prescription;empirical prescription- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-02-09
Review
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