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Issue 10 ， 2021
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Effect of Herbal Medicines in Wuzi Yanzong Wan Processed with Salt-water on Apoptosis of Spermatogenic Cells in Rats
Abstract：ObjectiveTo observe the effect of Wuzi Yanzong Wan made of different processed products on the apoptosis of spermatogenic cells in rats with kidney essence deficiency， and explore its protective effect on spermatogenic cells.MethodSD rats were randomly divided into the blank group， model group， whole raw product group， pharmacopoeia group and salt-processed product group， with 8 rats in each group. The kidney essence deficiency model was replicated by giving tripterygium glycoside tablets （the dose of 20 mg·kg-1）. The flow cytometry （FCM） was used to analysis the apoptosis of spermatogenic cells in testis， the immunohistochemistry （IHC） and Western blot were used to detect the expression levels of B-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax） in the testis. High performance liquid chromatography （HPLC） was used to compare the contents of eight components （chlorogenic acid， ellagic acid， hyperoside， isoquercitrin， verbascoside， astragalin， kaempferol and schisandrin） in Wuzi Yanzong Wan made of different processed products， the mobile phase was composed of acetonitrile （A）-0.4% phosphoric acid aqueous solution （B） for gradient elution （0-5 min， 5%-15%A； 5-10 min， 15%-17%A； 10-25 min， 17%A； 25-35 min， 17%-26%A； 35-60 min， 26%-56%A）， the detection wavelength was set at 254 nm.ResultCompared with the model group， the total apoptosis rate of spermatogenic cells， protein expression of Bax and Bcl-2 in each administration group were improved. Among them， the pharmacopoeia group and salt-processed product group had significant effects （P<0.01）， and the improvement effect of the pharmacopoeia group and salt-processed product group was significantly better than that of the whole raw product group （P<0.05）. The contents of chlorogenic acid， hyperoside， isoquercitrin and verbascoside in Wuzi Yanzong Wan were increased after the herbal medicines being processed with salt-water. The content of ellagic acid in the salt-processed product group increased， while it decreased in the pharmacopoeia group. The contents of verbascoside， astragalin， kaempferol and schisandrin in samples from the salt-processed product group were greater than those in samples from the pharmacopoeia group.ConclusionWuzi Yanzong Wan may reduce the apoptosis of spermatogenic cells in rat testis by inhibiting the expression of Bax and promoting the expression of Bcl-2， and exert its effect of nourishing kidney and enriching essence. The enhanced anti-spermatogenic effect of Wuzi Yanzong Wan after processing may be related to the changes in chemical composition content after processing.Keywords：Wuzi Yanzong Wan;processing with salt-water;deficiency of kidney essence;apoptosis of spermatogenic cells;B-cell lymphoma-2 （Bcl-2）;Bcl-2 associated X protein （Bax）;chemical composition- 28
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/
β -catenin and TGF-β 1/Smad Signal PathwayAbstract：ObjectiveTo study the protective effect of Xiayuxue Tang on adenine-induced renal fibrosis model in rats and its impact on Wnt/β-catenin and transforming growth factor β1（TGF-β1）/Smad signal pathway.MethodA total of 50 SPF-grade male SD rats were randomly divided into 5 groups： the normal group， the model group， the losartan group （9 mg·kg-1） and low and high dose （2.43，4.86 g·kg-1） of Xiayuxue Tang groups. The rat model of renal fibrosis was established by ig administration adenine （250 mg·kg-1） for 24 consecutive days. The rats were then given the corresponding drugs for 30 consecutive days. The levels of serum creatinine（SCr） and blood urea nitrogen （BUN） were measured by enzyme-linked immunosorbent assay（ELISA）. The histopathological changes of renal tissues in rats were observed by hematoxylin and eosin （HE） staining. The collagen deposition in rat renal tissue was observed by Masson staining； the protein expression levels of Wnt5a， Wnt5b， β-catenin， TGF-β1， Smad4， Smad7 in renal tissue were detected respectively by immunohistochemistry（IHC） and Western blot.ResultCompared with the normal group， the results of each experimental group showed that SCr and BUN levels significantly increased in the model group （P<0.01）. SCr and BUN levels decreased significantly after the intervention with the Xiayuxue Tang （P<0.01）. Compared with the normal group， HE and Masson staining results showed that rats in the model group had severe renal interstitial damage and massive deposition of renal interstitial collagen. The renal interstitial tubule injury was relieved after the intervention with the Xiayuxue Tang， and the renal interstitial collagen deposition decreased. The results of IHC and Western blot showed that compared with the normal group， the expressions of Wnt5a， β-catenin， TGF-β1 protein in the kidney of rats up-regulated （P<0.01）， while the expressions of Wnt5b and Smad7 protein down-regulated （P<0.01）. After the intervention with Xiayuxue Tang， the expressions of Wnt5a， β-catenin， TGF-β1 protein down-regulated （P<0.01）， while the expressions of Wnt5b and Smad7 protein up-regulated（P<0.01）. There was no significant difference between the low-dose and high-dose groups with Xiayuxue Tang.ConclusionXiayuxue Tang has the protective effect on RIF rats induced by adenine， and its mechanism is related to the inhibition of Wnt/β-catenin and TGF-β1/Smad signal pathway.Keywords：Xiayuxue Tang;renal fibrosis;Wnt/β-catenin;transforming growth factor β1/Smad- 18
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Anti-inflammatory Mechanism of Wuwei Xiaoduyin on IgA Nephropathy Rats Based on NF-
κ B Inflammatory Signaling PathwayAbstract：ObjectiveTo observe the effect of Wuwei Xiaoduyin on the nuclear factor-κB （NF-κB） signaling pathway in immunoglobulinA nephropathy（IgAN） rats， and to explore its mechanism of action in the treatment of IgA nephropathy.MethodThe 40 SD rats were randomly divided into control group， model group， benazepril group （10 mg·kg·d-1） and Wuwei Xiaoduyin group （2.75 g·kg·d-1）， with 10 rats in each group. The IgA nephropathy rat model was established by intragastric administration of bovine serum albumin （BSA）， subcutaneous injection of carbon tetrachloride （CCl4） and tail vein injection of lipopolysaccharide （LPS） for 9 weeks. The rats in each group were given corresponding doses of drugs by gavage， while the rats in the control group and model group were given the same amount of normal saline for successive 28 days. The levels of 24-hour urinary protein （UTP）， serum creatinine （SCr）， blood urea nitrogen （BUN） and serum albumin （ALB） were detected. The contents of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and interleukin-6 （IL-6） in serum were detected by enzyme-linked immunosorbent assay （ELISA）， the hematoxylineosin staining （HE）， immunofluorescence and transmission electron microscopy were used to observe the renal pathological changes， the expressions of IL-6， IκB kinase β （IKKβ）， phosphorylated IκB kinase β （p-IKKβ）， NF-κB inhibitor protein α （IκBα）， phosphorylated NF-κB inhibitor protein α （p-IκBα）， NF-κB p65 and p-NF-κB p65 were detected by immunohistochemistry （IHC）， real-time PCR （RT-PCR） and Western blot， respectively.ResultCompared with the control group， the level of UTP in the model group significantly increased （P<0.01）， cultured glomerular mesangial cells proliferated， mesangial matrix and electronic dense deposit increased， mesentery thickened. A large amount of IgA was deposited in the glomerular mesangial area and showed irregular particles and mass distribution， the levels of TNF-α， IL-1β， IL-6 in serum significantly increased （P<0.01）， the expression levels of IL-6， IKKβ， p-IKKβ， NF-κB p65 and p-NF-κB p65 in renal tissue significantly increased （P<0.01）.Compared with the model group， the levels of UTP in each administration group significantly decreased （P<0.01）， and the renal tissue injury alleviated， the levels of TNF-α， IL-1β， IL-6 in serum significantly decreased （P<0.01）， the expressions of IL-6， IKKβ， p-IKKβ， IκBα， p-IκBα， NF-κB p65 and p-NF-κB p65 in the renal tissue significantly decreased （P<0.01）. There were no significant differences in serum creatinine， blood urea nitrogen and serum albumin among the groups.ConclusionWuwei Xiaoduyin can reduce proteinuria in IgA nephropathy rats， and its mechanism may be related to the inhibition of NF-κB signaling pathway and the over expression of related inflammatory factors.Keywords：immunoglobulin （Ig）A nephropathy;Wuwei Xiaoduyin;nuclear factor-κB （NF-κB）;inflammatory response;proteinuria- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Effect of Huanglian Jiedutang on Learning and Memory Ability and Cholinergic System in AD Rats Induced by A
β 1-42Abstract：ObjectiveTo investigate the effects of Huanglian Jiedutang on learning and memory ability and the cholinergic system in Alzheimer's disease（AD） rats induced by amyloid β-protein（Aβ）1-42.MethodSixty male SD rats were divided into normal group， model group， huperzine A group （2.1×10-5 g·kg-1）， high-， medium- and low dose of Huanglian Jiedutang groups （6，3，1.5 g·kg-1）. AD rat model was replicated by hippocampal injection of Aβ1-42. After 4 weeks of treatment， Morris water maze test was performed. Hematoxylineosin （HE） staining was used to observe the pathological changes of rat hippocampus. Sampling blood from abdominal aorta was taken. Acetylcholine （ACh）， acetylcholinesterase （AchE） and choline acetyltransferase （ChAT） in serum and hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of hippocampal α7 nicotinic acetylcholine receptor （α7nAChR） protein was detected by Western blot. The expression of hippocampal α7nAChR mRNA was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）.ResultCompared with the normal group， there were obvious pathological changes in the model group，such as neuron necrosis in the cerebral cortex，pyramidal cell or granular cell necrosis in the hippocampus，disorder of arrangement and inflammatory cell infiltration，prolonged escape latency，decreased escape platform times，decreased residence time in the effective area and swimming path in the effective area （P<0.05，P<0.01）. The contents of α7nAChR mRNA，ACh，AchE，ChAT，α7nAChR in the hippocampus decreased （P<0.01）. Compared with the model group，the escape latency of the middle dose group was shorter （P<0.05）， the escape platform times，the swimming path in the effective area and the residence time in the effective area increased （P<0.05，P<0.01）， the contents of serum ACh，ChAT， hippocampal AchE，ChAT and α7nAChR increased （P<0.05，）. The expression of hippocampal α7nAChR protein significantly increased （P<0.01）， the residence time of effective area in high dose group was prolonged （P<0.01）， the times of escape platform increased，and the contents of serum ACh，ChAT and hippocampal ACh，AchE，α7nAChR protein and α7nAChR mRNA increased （P<0.05）.ConclusionHuanglian Jiedutang can significantly improve the learning and memory ability of AD rats induced by Aβ1-42，and its mechanism may be related to the improvement of cholinergic system damage and enhancement of cholinergic system function induced by Aβ1-42.Keywords：Huanglian Jiedutang;Alzheimer's disease;Cholinergic system;α7 nicotinic acetylcholine receptor （α7nAChR）- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20
Classic Prescriptions
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Experimental Study of Yuxuebi Tablets by Inhibiting Peripheral Inflammation to Relieve Hyperalgesia and Foot Swelling in Mice with Chronic Inflammatory Pain
Abstract：ObjectiveTo observe the effect of Yuxuebi tablets on hyperalgesia and foot swelling in mice with chronic inflammatory pain， and to explore the preliminary mechanism of action.MethodA mouse model of chronic inflammatory pain was established with left plantar injection of complete Freund's adjuvant （CFA）. The mice were divided into model group， positive drug ibuprofen group （91 mg·kg-1）， Yuxuebi tablets low， medium and high dose groups （55， 110， 220 mg·kg-1），with the sham operation group as the control. After successful modeling， the daily dose was divided into two doses in the morning and evening by gavage to give Yuxuebi tablets or ibuprofen to the stomach for a total of 19 days. On the 18th day after the administration， the thermal pain threshold was detected by the hot plate method. On the 19th day， the standard Von Frey fiber needle was used to detect the mechanical pain threshold of the mice， and the degree of foot swelling was scored and photographed. The liquid-phase suspension chip technology was used to quantitatively analyze 36 classic broad-spectrum inflammation-related factors like inflammatory factors and receptors. Bioinformatics were used to screen core targets and perform enzymelinked immunosorbent assay （ELISA） detection.ResultCompared with the sham operation group， the mechanical pain threshold and foot swelling score of the model froup significantly increased （P<0.01）， the latent time of heat sensitivity significantly decreased（P<0.01）， the expressions of 30 inflammatory factors in the foot increased（P<0.05）. Compared with the model group， the high dose of Yuxuebi tablets significantly reduced the mechanical pain threshold and foot swelling score of mice with chronic inflammatory pain（P<0.01）， significantly increased the latent time of heat sensitivity（P<0.05）， and reduced the expressions of 30 inflammatory factors in the foot（P<0.05）， among which tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and C-C chemokine ligand 2 （CCL2） were the core targets screened out， and the expressions of TNF-α， IL-17A， and CCL2 significantly decreased （P<0.01）.ConclusionYuxuebi tablets can relieve hyperalgesia and foot swelling in mice with chronic inflammatory pain， and its mechanism may be related to the inhibition of the expressions of peripheral inflammatory factors such as TNF-α， IL-17A， and CCL2 .Keywords：Yuxuebi Tablets;chronic inflammatory pain;anti-inflammatory;hyperalgesia;swelling;inflammatory factors- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Effect of Fuzheng Kangai Decoction on Immune Regulation and Inhibition of Tumor Growth in Rats with Ovarian Carcinoma
Abstract：ObjectiveTo explore the effect of Fuzheng Kangai decotion （FZKAD） on the immune regulation and the inhibition of tumor growth in rats with ovarian carcinoma.MethodKunming mice were randomly divided into normal group， lentinan （0.05 g·kg-1） group， and high （27.3 g·kg-1）， medium （13.65 g·kg-1） and low （6.825 g·kg-1） dose groups of FZKAD， with 10 mice in each group， serum hemolytic value （HC50）， antibody-forming cells and the phagocytosis of mononuclear macrophages were measured. Fischer 344 rat xenograft model was established through inoculation of NUTU-19 cell in the right axilla， and the model rats were randomly divided into model group， cisplatin group （0.002 g·kg-1）， and high （18.9 g·kg-1）， medium （9.45 g·kg-1）， and low （4.725 g·kg-1） dose groups of FZKAD， with 10 rats in each group， in addition， 10 healthy rats were randomly selected as the normal group. Tumor quality， tumor inhibition rate， T lymphocyte subsets， and expressions of serum cytokines， enhancer binding protein homologous protein 1（XBP1） and enhancer binding protein homologous protein （CHOP） protein in tumor tissues were detected after 14 days of administration.ResultCompared with normal group， HC50， level of antibody-forming cells， phagocytic index and phagocytic activity of mice in high， medium and low-dose groups of FZKAD were significantly increased （P<0.05， P<0.01）. Tumor quality and XBP1 protein expression in high， medium and low-dose groups of FZKAD were significantly decreased （P<0.01） compared with the model group， while the tumor inhibition rate， CD4+， CD8+ T cell ratio， CD4+/CD8+ ratio， tumor necrosis factor-α （TNF-α）， interleukin-2 （IL-2）， γ-interferon （IFN-γ） expression and CHOP protein expression were significantly increased （P<0.05， P<0.01）.ConclusionFZKAD can improve the immune function of normal mice and inhibit the tumor growth in rats with ovarian carcinoma， and the immunity regulation effect is the main mechanism.Keywords：Fuzheng Kangai decoction （FZKAD）;immunity regulation;ovarian carcinoma;T cell subset;cytokines- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Intervention Mechanism of Yishen Huayu Prescription on Glomerular Podocyte Injury in Diabetic Nephropathy Rats Based on EMT Regulated by Wnt/
β -catenin PathwayAbstract：ObjectiveTo investigate the intervention mechanism of Yishen Huayu prescription on glomerular podocyte injury in diabetic nephropathy （DN） rats based on epithelialmesenchymal transition （EMT） regulated by Wnt/β-catenin pathway.MethodThe 60 SD rats were divided into control group， model group， Wnt-C59 group （0.03 g·kg-1 Wnt/β-catenin pathway inhibitor）， low-dose group （8 g·kg-1）， medium-dose group （16 g·kg-1） and high-dose group （32 g·kg-1）. After 12 weeks， various indexes ， including general signs， serum creatinine （SCr）， blood urea nitrogen （BUN）， renal index， urinary protein， blood glucose， renal pathological changes， podocyte and expressions of glomerular basement membrane injury and podocyte injury related proteins ［nephrin， synaptopodin］， Wnt/β-catenin pathway related proteins （Wnt1， β-catenin）， podocyte EMT related protein ［α-smooth muscle actin （α-SMA）， E-cadherin］， were compared between groups.ResultCompared with the control group， the renal tissue in the model group showed significant pathological changes， including diffuse thickening of glomerular mesangial matrix and severe foot process fusion， and a significant increase in SCr， BUN， renal indexes， urinary protein， blood glucose， Wnt1， β-catenin， and α-SMA expression levels （P<0.05） as well as a significant decrease in nephrin， synaptopodin and E-cadherin expression levels（P<0.05）. Compared with model group， SCr， BUN， renal index， urinary protein， blood glucose， Wnt1， β-catenin， and α-SMA expression levels in each intervention group significantly decreased （P<0.05）， while the expression levels of nephrin， synaptopodin and E-cadherin significantly increased （P<0.05）. Among intervention groups， the improvement of above indexes in high-dose Yishen Huayu prescription group was the most obvious （P<0.05）， which was similar to the effect in Wnt-C59 group.ConclusionYishen Huayu prescription prevents podocyte EMT by inhibiting Wnt/β-catenin pathway， thereby repairing glomerular podocyte injury in rats with diabetic nephropathy.Keywords：diabetic nephropathy;glomerular podocyte injury;Wnt/β-catenin pathway;epithelialmesenchymal transition （EMT）;Yishen Huayu prescription;Intervention mechanism- 42
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20
Pharmacology
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Efficacy and Mechanism of Qingre Lishi Prescription in Treating Children with Acute Bacterial Lower Urinary Tract Infection of Bladder Damp-heat Syndrome
Abstract：ObjectiveTo observe the efficacy of Qingre Lishi prescription in treating children with acute bacterial lower urinary tract infection of bladder damp-heat syndrome， and to explore its mechanism of action.MethodEighty children with acute bacterial lower urinary tract infection of late bladder damp-heat syndrome who were admitted to the Affiliated Hospital of Changchun University of Chinese Medicine were divided into control group and observation group， 40 cases in each group. Patients in control group were given Bazhengsan for oral treatment on basis of basic treatment， while patients in observation group were given Qingre Lishi prescription for oral administration plus external washing treatment. After two weeks of treatment， the clinical and etiological effect， traditional Chinese medicine （TCM） syndrome scores， antipyretic time and urinary negative time， adverse reactions， and urine pathogens （Escherichia coli， Enterococcus faecalis， Strange proteus， Klebsiella pneumoniae）， serum inflammatory factor indicators ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， calcium lowering PCT， white blood cell count （WBC） and serum C-reactive protein （CRP）］， immune function indicators ［T cell subsets （CD3+， CD4+， CD8+） and complement （C3， C4）］ were comapred between two groups.ResultThe clinical efficacy of observation group was 92.50% （37/40）， which was significantly higher than 65.00% （26/40） in control group （χ2=9.038， P<0.01）， the etiological efficacy of observation group was 87.50% （35/40）， which was significantly higher than 60.00% （24/40） in control group （χ2=7.813， P<0.01）. After treatment， the scores of TCM syndromes of the two groups were significantly reduced （P<0.05）. The scores of fever， frequent urination， urgent urination， painful urination， difficulty urinating and abdominal pain in two groups were significantly lower than those before treatment （P<0.05）， and the TCM syndrome scores in observation group were lower than those in control group （P<0.05）， the antipyretic time and urinary bacteria turning negative time of observation group were significantly lower than those in control group （P<0.05）， the Escherichia coli， Enterococcus faecalis， Proteus mirabilis， Klebsiella pneumoniae pathogenic bacteria detected in both groups were both significantly lower than those before treatment （P<0.05）. After treatment， the levels of inflammatory factors such as TNF-α， IL-6， IL-8， PCT， WBC and CRP in two groups were significantly lower than those before treatment （P<0.05）， the immune function of the two groups was significantly improved， and the levels of CD3+， CD4+， C3， and C4 in observation group were higher than those in control group（P<0.05）， and the CD8+ level was lower than that in control group （P<0.05）. The incidence of adverse reactions had no significant difference between two groups.ConclusionQingre Lishi prescription has good clinical effect in treating children with acute bacterial lower urinary tract infection with bladder damp-heat syndrome. It can improve TCM syndromes and clinical symptoms. Its mechanism is related to inhibiting pathogenic bacteria， reducing inflammation， and improving immune function， and it has good security.Keywords：Qingre Lishi prescription;children with urinary tract infection;bladder damp-heat syndrome;inflammatory factor;bacteria;immune function;mechanism- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Clinical Efficacy on Erchentang Combined with Sanzi Yangqintang in Treatment of Cough Variant Asthma in Children with Phlegm Evil Accumulation Lung Syndrome
Abstract：ObjectiveTo observe the clinical efficacy of Erchentang combined with Sanzi Yangqintang in the treatment of cough variant asthma （CVA） in children with phlegm-evil accumulation lung syndrome and its influence on airway inflammation and airway hyperresponsiveness （AHR）.MethodA total of one hundred and sixteen children were randomly divided into observation group and control group 58 cases in each group. Patients in both groups took montelukast sodium chewable tablets orally， 5 mg/time， once daily， at night before bedtime. In observation group， patients took Erchentang and Sanzi Yangqintang modified granules orally. While patients in control group took Erchentang and Sanzi Yangqintang placebo granules orally. Treatment course continued six weeks for two groups. Before and after treatment， the cough symptom scores and phlegm evil accumulating lung syndrome scores were recorded every week. The cough remission time and cough disappearance time were recorded， followed up for 24 weeks to record cough recurrence. Leicester Cough quality of life questionnaire （LCQ） was scored before and after treatment. The ratio of induced sputum eosinophils （EOS） and the levels of interleukin-4 （IL-4）， IL-5， IL-12， IL-13 were measured before and after treatment. The cumulative doses of exhaled nitric oxide （FeNO） and methacholine （PD20） were measued before and after therapy. Safety evaluation was conducted.ResultThe scores of cough symptom and phlegm-evil accumulation lung syndrome at different time points were decreased gradually in two groups of children after treatment （Fcontrol group=5.277， Fobservation group=7.636，P<0.01）. The scores of cough symptom and phlegm-evil accumulation in the lung syndrome of observation group were lower than those in control group （P<0.01） at the same period. The durations of cough relief and cough disappearance in observation group were shorter than those in control group （P<0.01）. Within 24 weeks of follow-up， the recurrence rate of children in observation group was 68.97% （40/58）， lower than 84.48% （49/58） in control group （χ2=3.917，P<0.05）. Children in observation group had fewer relapses than those in control group （P<0.01）. The total LCQ scores and scores of all dimensions in observation group were higher than those in control group （P<0.01）. The EOS， IL-4， IL-5 and IL-13 levels in observation group were lower than the data in control group， and IL-12 level was higher than that in control group （P<0.01）. FeNO of children in observation group was lower than that in control group （P<0.01）， while PD20 was more than that of control group （P<0.01）. The total effective rate of clinical curative effect of children in observation group was 96.55% （56/58）， which was higher than 82.76% （48/58） in control group （χ2=5.948，P<0.05）.ConclusionErchentang combined with Sanzi Yangqintang for children with CVA phlegm evil accumulation lung syndrome can further control the symptoms of cough， shorten the course of cough， improve the quality of life， and reduce airway inflammation and AHR， reduce the recurrence rate. The clinical efficacy is better than using montelukast only， and it is safe and has good clinical value.Keywords：cough variant asthma;children;phlegm evil accumulation lung;Erchentang;Sanzi Yangqintang;airway inflammation;airway hyperresponsiveness- 12
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Clinical Study on Dialectical Treatment of Modified Xiangsha Liu Junzitang to Diabetes Gastroparesis with Weakness Syndrome of Spleen and Stomach
Abstract：ObjectiveThis study aims to investigate the clinical efficacy of Modified Xiangsha Liu Junzitang in the treatment of diabetic gastroparesis （DGP） and its influence on gastrointestinal hormones and oxidative stress.MethodIn this study， 128 patients were randomly divided into control group （64 cases） and observation group （64 cases） . Patients in two groups took domperidone tablets orally 30 minutes before meals， 10 mg/time， 3 times/day. Patients in control group took Shenling Baizhusan San， 6 g/time， twice a day. Patients in observation group were prescribed addition and subtraction therapy of Modified Xiangsha Liu Junzitang， 1 dose/day. The course of treatment for both groups was 4 weeks. Before and after treatment， scores of gastroparesis cardinal symptom index （GCSI）， and gastric emptying test and electrogastrogram were noted. Before the treatment， scores of traditional Chinese medicine （TCM） syndrome and health survey summary were graded（SF-36）. The levels of gastrin （GAS）， motilin （MTL）， vasoactive intestinal peptide （VIP）， somatostatin （SS）， superoxide dismutase （SOD）， reactive oxygen species （ROS） and malondialdehyde （MDA） were measured before and after treatment. And adverse reactions during treatment were recorded.ResultThe scores of postprandial abdominal distension/early satiety， nausea and vomiting， abdominal distention and the total scores of GCSI in the observation group were lower than those in control group （P<0.01）. The gastric emptying rate in observation group was higher than that in control group （P<0.01）， and the score of TCM syndromes was lower than that of control group （P<0.01）. The scores of SF-36 in observation group were higher than those in control group （P<0.01）. The frequency of gastric electricity and gastric electric vibration before and after the meal in observation group were higher than that in control group （P<0.01）. The levels of GAS， MTL， VIP， ROS and MDA in observation group were lower than those in control group （P<0.01）， while the levels of SS and SOD were higher than that of control group （P<0.01）. The total effective rate in observation group was 93.75% （60/64）， which was higher than 79.69% （51/64） （χ2=5.494， P<0.05） in control group （P<0.01）. And no adverse reactions were found in the clinical observation.ConclusionModified Xiangsha Liu Junzitang combined with prokinetic drugs in the treatment of DGP patients can reduce the clinical symptoms of DGP， enhance gastrointestinal motility， improve the gastric emptying rate， improve the quality of life， regulate the level of gastrointestinal hormones， and reduce the damage of autonomic nerve caused by oxidative stress， with good comprehensive clinical effect and safety in application.Keywords：diabetes gastroparesis;Xiangsha Liu Junzitang;spleen and stomach weakness;gastric emptying;gastrointestinal hormones;oxidative stress- 10
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Clinical Efficacy on Addition and Subtraction Therapy of Zhibai Dihuangwan Combined with Wulingsan on Children with Refractory Nephrotic Syndrome
Abstract：ObjectiveThis study aims to investigate the clinical effect of addition and subtraction therapy of Zhibai Dihuangwan combined with Wulingsan in the treatment of refractory nephrotic syndrome （RNS） with Yin deficiency of liver and kidney and its regulatory effect on immune inflammatory response.MethodIn this study， 108 children were randomly divided into observation group （54 cases） and control group （54 cases）. Patients in two groups were treated with prednisone acetate tablets combined with tacrolimus capsules . Patients in control group took Liuwei Dihuang oral liquid， 5-10 mL/time， twice a day. Patients in control group were prescribed the addition and subtraction therapy of Zhibai Dihuangwan combined with Wulingsan， 1 dose/day. The course of treatment for both groups was 6 months. The 24 h urine total protein （24 h-UTP）， serum albumin （ALB）， serum creatinine （Scr）， blood urea nitrogen （BUN）， total cholesterol （TC）， triglyceride （TG）， low density lipoprotein （LDL）， high density lipoprotein （HDL）， liver and kidney Yin deficiency syndrome score， fibrinogen （FIB）， D-dimer （D-D）， prothrombin time （PT） and activated partial thromboplastin time （APTT） were compared before and after treatment. Also， tumor necrosis factor-α （TNF- α）， interleukin-6（IL-6）， IL-10， IL-17， CD4+ and CD8+， helper T lymphocytes17 （Th17）， regulatory T cell （Treg） were detected before and after treatment， and CD4+/CD8+ and Th17/Treg were also calculated.ResultThe levels of 24 h-UTP， TC， TG， LDL， FIB， D-D， TNF-α， IL-10， IL-6 and IL-17 in observation group were all lower than those in control group （P<0.01）， and the levels of CD8+， Th17 and Th17/Treg were alsolower than those in control group （P<0.05）. While the levels of HDL，ALB， CD4+， Treg and CD4+/CD8+ in observation group were higher than those in control group （P<0.05）. The comprehensive efficacy in observation group was better than that in control group （Z=2.02， P<0.05）， and the traditional Chinese medicine （TCM） syndrome efficacy of observation group was better than that of control group （Z=2.10， P<0.05）.ConclusionBased on the treatment of hormone combined with Tacrolimus， Zhibai Dihuangwan combined with Wulingsan can reduce urinary protein， improve lipid metabolism disorder and hypercoagulability， and regulate immune inflammatory reaction in patients with RNS and Yin deficiency of liver and kidney， with remarkable comprehensive effect and TCM syndrome effect.Keywords：refractory nephrotic syndrome;children;Yin deficiency of liver and kidney;Zhibai Dihuangwan;Wulingsan;immune function;inflammatory factors- 14
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20
Clinic
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Metabolomics Analysis of Chloriti Lapis on Brain Tissue of PTZ-kindled Epileptic Rats
Abstract：ObjectiveTo explore the possible mechanism of Chloriti Lapis in the treatment of epilepsy by the metabonomics of brain tissue in pentylenetetrazol （PTZ）-kindled epileptic rats treated with Chloriti Lapis.MethodThe epileptic animal model in rats was established by PTZ kindling， and the rats were divided into the control group， model group， carbamazepine group and Chloriti Lapis group. The brain tissue samples were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry（UPLC/Q-TOF-MS）， and the experimental results were statistically analyzed by partial least squares-discriminant analysis （PLS-DA） and SPSS 18.0.ResultThe metabolic fingerprints and metabolic profiles of the rat brain tissue were established， which showed that the metabolic profiles of each group had changed significantly and could be separated well among the groups. Moreover， the Chloriti Lapis group had a tendency to be closer to the control group than the carbamazepine group. Seven differential metabolites were screened， including phosphatidylserine （PS） （18∶0/18∶0）， L-glutamic acid， docosahexaenoyl ethanolamide， arachidonic acid， glucosylsphingosine， cholestane-3，7，12，24，25-pentol and lysophosphatidylcholine （LysoPC） （P-18∶0）. Except for docosahexaenoyl ethanolamide and LysoPC （P-18∶0）， Chloriti Lapis had significant intervening and regulating effects on the other five differential metabolites. There were 12 possible metabolic pathways that affected the metabolic disorder of PTZ-kindled rats， and 3 important metabolic pathways （pathway impact>0.1）， namely， D-glutamine and D-glutamate metabolism， alanine， aspartate and glutamate metabolism， and arachidonic acid metabolism， among which D-glutamine and D-glutamate metabolism was the most important metabolic pathways.ConclusionFrom this point of view， Chloriti Lapis has a clear intervention effect on PTZ-kindled epileptic rats， which may be related to the intervention of the above differential metabolite contents and related metabolic pathways. It can reduce the toxic effect of excitatory neurotransmitters on neurons in brain tissue and inhibit the development of inflammation in brain tissue， so as to maintain the biological function of brain cells and slow down the occurrence of epilepsy.Keywords：mineral Chinese medicines;Chloriti Lapis;epilepsy;pentylenetetrazol （PTZ）;brain tissue;metabonomics;mechanism of action- 19
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20
Drug Metabolism
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GC-IMS Analysis of Volatile Components in Rhododendri Mollis Flos at Different Flowering Stages
Abstract：ObjectiveThe volatile components of Rhododendri Mollis Flos were determined and the differences of volatile components at different flowering stages were compared and analyzed.MethodGas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile components in Rhododendri Mollis Flos at different flowering stages （bud stage， initial flowering stage， half-flowering stage， blooming stage and late blooming stage）. GC-IMS spectra combined with cluster analysis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to compare the differences and similarities of volatile components in different flowering stages.ResultA total of 70 volatile components in Rhododendri Mollis Flos at different flowering stages were detected， among which 67 were common components， and 47 were identified qualitatively， mainly alcohols， esters and aldehydes. Carveol was a special component at the late blooming stage. The content of alpha-terpineol is the highest at the initial flowering stage， but not at the blooming stage and late blooming stage. The relative contents of the active ingredients ［6-methyl-5-hepten-2-one， nonanal， alpha-terpineol， 1，8-cineole， linalool oxide， 1-octen-3-ol， （E）-3-hexenol］ showed a decreasing trend during flowering stages. GC-IMS spectra showed that the samples at different flowering stages had their own characteristic peak regions， and also had common regions. The results of cluster analysis， PCA and OPLS-DA all showed that the samples at different flowering stages were distinguishable. OPLS-DA was used to screen 19 different components to distinguish different flowering stages， including γ-butyrolactone， 1，8-cineole， ethyl hexanoate， etc.ConclusionRhododendri Mollis Flos samples at different flowering stages can be distinguished obviously， and the active substances in the volatile components are gradually dissipated with the degree of flower opening， which can provide reference for the improvement of material basis and the study of different flowering stages of Rhododendri Mollis Flos.Keywords：Rhododendri Mollis Flos;volatile components;flowering stage;chemometrics;gas chromatography-ion mobility spectrometry （GC-IMS）;carveol;alpha-terpineol- 10
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Analysis of Effective Terpenoids in Xinjiang
Pleurotus ferulae Against Esophageal Carcinoma by UPLC-Q/TOF-MS Technique Enhanced PublicationAbstract：ObjectiveTo discover the effective terpenoids in Xinjiang Pleurotus ferulae with the activity of anti-esophageal carcinoma.MethodBy screening the activity of human esophageal cancer Eca109 cells， the ethyl acetate extract phase of P. ferulae ethanol extract （PFEP-E） was separated and purified by silica gel chromatography and preparative thin layer chromatography. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q/TOF-MS） combined with online network databases such as Metlin， MassBank， PubChem and related literature were used to identify the effective elution sites and analyze their contents.ResultThe elution fraction （Fr2-3∶1） of petroleum ether-ethyl acetate （3∶1） on the silica gel column had the strongest inhibitory activity on the proliferation of human esophageal cancer Eca109 cells. The component analysis showed that 24 effective terpenoids were identified under positive ion mode， and 28 effective terpenoids were identified under negative ion mode， a total of 52 terpenoids were identified， which were isolated from this edible fungus for the first time. Content of total terpenoids in Fr2-3∶1 were 62.88 mg·g-1， including 2 monoterpenoids， 5 sesquiterpenoids， 15 diterpenoids and 30 triterpenoids， accounting for 1.32%， 12.04%， 47.55%， 39.09% of the total terpenoids， respectively. Diterpenoids and triterpenoids were the main components of the effective terpenoids in P. ferulae， accounting for 86.64% of the total terpenoids. Gibberellins were the main diterpenoids， accounting for 79.70% of the total diterpenoids， triterpenoids were mainly ganoderic acids， accounting for 29.25% of the total triterpenoids. The results of methyl thiazolyl tetrazolium （MTT） test showed that gibberellin A3 and gibberellin A5 had weak anti-esophageal cancer activity， while gypsogenin and oleanolic acid had strong anti-esophageal cancer activity.ConclusionThe effective terpenoids of P. ferulae against esophageal cancer are triterpenoids mainly composed of ganoderic acids， which can provide theoretical basis for the development of terpenoids of P. ferulae as anti-tumor drugs and the development of functional foods， and help to effectively improve the additional output value of P. ferulae.Keywords：Pleurotus ferulae;terpenoids;ganoderic acids;esophageal carcinoma;ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q/TOF-MS）- 14
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Analysis of Volatile Organic Compounds in Rhizosphere Soil of
Rehmannia glutinosa Under IntercroppingZea mays Based on GC-MS MetabonomicsAbstract：ObjectiveTo explore the composition characteristics of rhizosphere soil under Rehmannia glutinosa-Zea mays intercropping model，and screen out special signal substances in rhizosphere soil of R. glutinosa under intercropping Z. mays， so as to provide the basis for the study of allelopathic substances in continuous cropping obstacle of R. glutinosa.MethodIn this experiment，rhizosphere soils of R. glutinosa under Z. mays intercropping and R. glutinosa single cropping models in July，August，September and October were taken as the research objects， and the volatile organic compounds in ethyl acetate fraction were analyzed by gas chromatography-mass spectrometry （GC-MS）. Principal component analysis （PCA）， hierachical cluster analysis （HCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） analysis were performed on the data by SIMCA 14.1 to screen out potential differences in volatile organic compounds between the two models.ResultThe types of volatile organic compounds in intercropping and single cropping models were mainly hydrocarbons， alcohols， esters， ketones， amides， acids and other substances. Specifically， the average relative contents of hydrocarbons，esters and amides in intercropping model were 58.46%，32.15% and 5.42% respectively，while the relative contents of hydrocarbons，esters and amides in single cropping model were 37.27%，36.11% and 21.13%. The results of PCA and HCA showed that the characteristics of volatile organic compounds in the ethyl acetate fraction of rhizosphere soil under intercropping and single cropping models could be clearly divided into two categories，the screening results of potential differential components based on OPLS-DA analysis indicated that various components， such as dibutyl phthalate，（Z）-9-oleamide，β-caryophyllene，dioctyl iso-phthalate， phthalate （2-propylamyl） diester， n-hexadecane，octodecane， n-heneicosane， were screened from rhizosphere soil under the two models.ConclusionThe R. glutinosa-Z. mays intercropping model has certain effects on the volatile organic compounds in the rhizosphere soil of R. glutinosa，and the effect of the selected components on the growth and quality characteristics of R. glutinosa still need to be further studied.Keywords：intercropping pattern;Rehmannia glutinosa;Zea mays;rhizosphere soil;gas chromatography-mass spectrometry （GC-MS）;volatile organic compounds- 12
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Analysis on Seed Quality Grading Standard of
Belamcanda chinensis Abstract：ObjectiveTo study the quality inspection standard of seeds of Belamcanda chinensis and establish the quality grading standard of seeds of B. chinensis.MethodThe purity of seeds of B. chinensis from different producing areas was analyzed，and the 1 000-grain weight，water content，viability and germination rate of seeds of B. chinensis with different diameters were determined after diameter classification. K-means was used for cluster analysis to preliminarily formulate the quality grading standard of seeds of B. chinensis.ResultThere were obvious regional differences in the size of seeds of B. chinensis. The particle size of seeds of B. chinensis of Xiaochang，Dawu and Huanggang Academy of Agricultural Sciences in Hubei Province was larger and mostly between 4.5 mm to 5.5 mm. The seeds of B. chinensis from Tuanfeng，Qujing，Yunnan，and Anguo，Hebei province had smaller particle sizes than those from the other three producing areas，which were mostly between 3.5 mm to 5.0 mm. Arils in seeds of B. chinensis were removed by 10% NaClO to effectively break seed dormancy and significantly improve the seed germination rate. On this basis，the seed diameter was taken as the main grading index，and the seed moisture content，viability，germination rate and purity were taken as important reference indexes. The quality of seeds of B. chinensis was preliminarily divided into three grades，grade Ⅰ：seed diameter≥5.5 mm，moisture content≤10%，viability≥94%，germination rate≥60%，and cleanliness≥93%；grade Ⅱ：seed diameter≥4.5 mm，moisture content≤10%，viability≥90%，germination rate≥55%，and cleanliness≥85%；and grade Ⅲ：seed diameter≥3.5 mm，moisture content≤10%，viability≥84%，germination rate≥45%，cleanliness≥80%.ConclusionIn this study，the quality grading standard of seeds of B. chinensis was preliminarily established to provide reference for the quality evaluation of seeds of B. chinensis and the breeding of improved varieties. In addition，the maturity and the storage time of seeds of B. chinensis have a greater impact on the quality of seeds，so it is recommended to select fully mature（dark black） seeds and new seeds for production.Keywords：Belamcanda chinensis;seed;germination percentage;quality inspection;quality classification- 11
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Herbal Textual Research on Mume Flos
Abstract：Mume Flos is a traditional Chinese medicinal material，with the effects of soothing the liver，resolving phlegm and dispelling stagnation. It was mainly used to treat globus hystericus，liver and stomach pain，loss of appetite，dizziness and scrofula. Mume Flos is native to China，with a long history of cultivation and application and complex and diverse varieties. There are hundreds varieties of Mume Flos，including fruiting Mei and flowering Mei. However，there was no ancient literature on which color of Mume Flos is the best traditional Chinese medicinal material among those with different colors，as well as relevant study report on the correlation between medicinal Mume Flos group and plant systematics. In order to define the origin，the author conducted the textual research on the changes in the origin，quality and producing areas of the Mume Flos in the past dynasties. According to the findings， traditional medicinal Mume Flos were mainly green calyx Mume Flos and white Mume Flos，and derived from flowering Mei of the true Mume branch. Among them， green calyx Mume Flos belonged to the green calyx group， while medicinal white Mume Flos belonged to the albo-plena group and the single-lobe group. The producing area of Mume Flos was first recorded in Sheng Nong's Herbal Classic，where now in southern Shaanxi province. After the Song dynasty，due to climate，social and economic factors，the producing areas of Mume Flos had continued to move southward from Shaanxi province to the Yangtze River and Dongting Lake basins. Till the Ming and Qing dynasties，the distribution of Mume Flos was also reported in Guangdong province and Hainan province. In modern times，due to the comprehensive impact of natural climate conditions and urbanization，the producing areas of medicinal Mume Flos had gradually changed from Sichuan province，Jiangsu province and Zhejiang province to southern Anhui province at present. In this paper，the textual research is conducted to define the origin and systematically summarize the changes in the producing areas of Mume Flos，so as to provide reference for defining the origin of Mume Flos and the groups of medicinal Mume Flos and making further development and utilization of resources.Keywords：Mume Flos;herbal textual research;color;change of producing areas- 12
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Textual Research on Ranae Oviductus
Abstract：Ranae Oviductus has a good tonic effect and is commonly used for both medicine and food. The use of Ranae Oviductus was confused because the origin of Ranae Oviductus was roughly recorded in ancient herbal literatures. In order to clarify the confusing literatures and trace the origin of Ranae Oviductus，this paper conducted a textual research on the name，origin，distribution，harvesting and processing，efficacy of the Chinese medicine by consulting ancient herbal books，modern literatures and monographs of traditional Chinese medicine. The results of the textual research showed that Ranae Oviductus belongs to Manchu medicine，which was first applied by the Manchu people because of its tonic effect. The original animal of Ranae Oviductus has many names，which are all translated from Manchu language. By analyzing the descriptions of Ranidae in various herbal books，it is concluded that the earliest description of the original animals of Ranae Oviductus appeared in the Shengjing Tongzhi compiled by Agui in the Qing dynasty. After summarization of the taxonomic changes of some species of Rana，the original animals of Ranae Oviductus were preliminarily determined as Rana dybowskii，R. amurensis and R. huanrenensis. We excluded R. huanrenensis by its size and R. amurensis by its poor quality. Therefore，the original animal of Ranae Oviductus is R. dybowskii，the main production area is northeast China and the best capture time is in October. Ranae Oviductus is often eaten after being stewed. The study can provide the effective basis for the identification of the original animal of Ranae Oviductus，the distribution of production area and the utilization of resources.Keywords：Ranae Oviductus;original animal;textual research;origin;efficacy- 12
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20
Pharmacy Fundamentals
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Analysis on Material Basis and Mechanism Difference of Antibacterial Effect of
Coptis chinensis and Its Flower Stalk Based on Secondary Metabolites and Network PharmacologyAbstract：ObjectiveTo explore the difference in antibacterial mechanism between Coptis chinensis and its flower stalk based on secondary metabolites and network pharmacology.MethodBased on the ultraperformance liquid chromatography mass spectrometry（UPLC-MS/MS） detection platform，the secondary metabolites database of C. chinensis and its flower stalk（MWDB） was built. The common database of metabolites information and the multivariate statistical analysis were used to study the differences of secondary metabolites between C. chinensis and its flower stalk and screen out 18 metabolites of the flower stalk and 11 metabolites of C. chinensis with a high content. BATMAN-TCM database was used to obtain the targets of component action，and their corresponding genes were inquired in the UniProt database. GeneCards was retrieved for antimicrobial genes，and the intersection genes of components and antimicrobials were obtained on Venny platform. Through DAVID gene ontology（GO） enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis，the mechanism of its action was predicted，and the results were visualized through histogram and advanced bubble diagram drawn by GraphPad Prism software and OmicShare database. The protein-protein interaction（PPI） network was constructed by STRING， database and the component-target-pathway network was constructed by Cytoscape 3.7.2 software. The antibacterial differences were compared based on the results of network pharmacology analysis.ResultThrough network pharmacology，the antibacterial active components of C. chinensis were 5 fewer than that of the flower stalk，55 more antibacterial targets than that of the flower stalk； quercetin and berberine were predicted to be the common components of the antagonistic action of C. chinensis and the flower stalk. Key genes involved in antimicrobial action were p38 Mitogen-activated protein kinase 14（MAPK14），catalase（CAT）； malaria and Toll-like receptor signaling pathway were different key pathways involved in antimicrobial activity.ConclusionC. chinensis and the flower stalk mainly exert the antibacterial effect in a multi-target and multi-pathway manner，which can offer new ideas and clues for the study of antibacterial mechanism of C. chinensis and the flower stalk，and provide a new development direction for the comprehensive development and rational application of the flower stalk resources.Keywords：network pharmacology;secondary metabolites;Coptis chinensis;C. chinensis flower stalk;antibacterial;ultra performance liquid chromatography mass spectrometry（UPLC-MS/MS）- 8
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Network Pharmacology-based Analysis on Mechanism of Aconiti Lateralis Radix Praeparata and Epimedii Folium in Treatment of Chronic Heart Failure
Abstract：ObjectiveTo explore the mechanism of the prescription consisting Aconiti Lateralis Radix Praeparata and Epimedii Folium in the treatment of chronic heart failure （CHF） based on network pharmacology，followed by verification in H9c2 myocardial cells with hypoxia-reoxygenation injury in vitro and in zebrafish with vascular endothelial growth factor receptor （VEGFR） tyrosine kinase inhibitor Ⅱ （VRI） -induced vascular insufficiency.MethodThe active ingredients in Aconiti Lateralis Radix Praeparata and Epimedii Folium were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），the corresponding target genes from the Universal Protein Resource （UniProt）， and the CHF-related targets from Online Mendelian Inheritance in Man （OMIM） and GeneCards. Both the active ingredient-potential target network and the active ingredient-CHF-related target network were generated using Cytoscape 3.6.1， followed by the protein-protein interaction （PPI） network construction and Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genome （KEGG） enrichment analysis based on MetaScape. H9c2 myocardial cells exposed to hypoxia-reoxygenation were selected for determining the proliferation-promoting effect by methyl thiazolyl tetrazolium （MTT） assay. The protein expression of B-cell lymphoma-2（Bcl-2）， Bcl-2-associated X protein（Bax），cysteinyl aspartate-specific protease-3（Caspase-3）， protein kinase B（PKB/Akt），phosphorylated protein kinase B（p-Akt），phosphorylated extracellular signal-regulated kinases 1/2 （p-ERK1/2），extracellular signal-regulated kinase 1/2 （ERK1/2）， and poly adenosine diphosphate ribose polymerase（PARP）was detected by Western blotting. The efficacy of the prescription in promoting angiogenesis was verified in a zebrafish model of VRI-induced vascular injury.ResultThere were 28 active ingredients for the prescription， 209 corresponding targets， 1 296 CHF-related targets， and 94 common gene targets shared by the prescription and CHF. PPI network clustering suggested that Aconiti Lateralis Radix Praeparata and Epimedii Folium alleviated CHF by interfering with cell differentiation and metabolism and angiogenesis. GO analysis revealed that CHF relief was achieved via the intervention in such biological processes as cell migration，vascular development， and angiogenesis. Pharmacodynamic experiments verified that Epimedii Folium （10 mg·L-1） alone and the prescription （10 mg·L-1）both enhanced the proliferation of H9c2 myocardial cells under the hypoxia-reoxygenation condition （P<0.05），while the latter also increased the expression of Bcl-2，Bcl-2/Bax， and PARP （P<0.05） and reduced the expression of Caspase-3， Akt， and ERK （P<0.05）. The prescription at the concentrations of 0.3 and 0.1 g·L-1 promoted angiogenesis （P<0.05）.ConclusionAconiti Lateralis Radix Praeparata and Epimedii Folium exert the therapeutic effect against CHF via multiple ingredients，multiple targets， and multiple channels. Such combination promotes the proliferation of H9c2 myocardial cells under hypoxic condition and protects zebrafish from vascular injury by up-regulating the expression of Bcl-2 and PARP，increasing Bcl-2/Bax ratio，and down-regulating the expression of Caspase-3，Akt， and ERK.Keywords：network pharmacology;chronic heart failure （CHF）;angiogenesis;Aconiti Lateralis Radix Praeparata;Epimedii Folium- 29
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Automatic Framework Acquisition and Visualization Analysis of Ancient Chinese Medicine Literature Relating to Tumor
Abstract：ObjectiveTo obtain ancient traditional Chinese medicine（TCM）literatures relating to tumor and visual analysis by an automatic framework tool， in order to systematically sort out the development of ancient Chinese medicine oncology.MethodBased on the database platform of ancient TCM books，names of tumor-related diseases in ancient TCM books were retrieved by Selenium WebDriver， an automation framework tool under Python 3.8. Lxml's etree library was used to parse the data. Statistics was made for "classification"， "authors"， "completion time" and "summary" of relevant ancient books automatically. After the data was checked and processed， Tableau 2019.2 software was used for data visualization analysis. And ancient Chinese medicine literatures relating to tumor were consulted at the database manually，with the dynasties as the clue，and the symptoms，etiology，pathogenesis and prognosis as the emphasis，this paper explores the development process of TCM oncology.ResultA total of 774 349 bytes of text data of 1 128 entries in 242 ancient books were included automatically. According to the findings， there were simple classification and time distribution of tumor diseases in ancient TCM books in the pre-Qin period， with a simple view on the pathogenesis of tumor diseases. From the Han dynasty to the Tang dynasty， the number of relevant literature records and the types and disease names had gradually increased，which further enriched the cognition of tumor nature，signs，classification methods，differential diagnosis；in Song and Ming dynasties，the proportion of Chinese prescription books and surgery books had increased gradually，with the largest number of abdominal organ tumor names among all dynasties；from Qing dynasty to the Republic of China，literatures relating to tumor name and classification were the most improved，and then the TCM tumor syndrome differentiation and treatment system had been formed.ConclusionIt was found that TCM oncology originated in the pre-Qin dynasty，and was improved in the Han and Tang dynasties， mature in the Song and Ming dynasties and completed in the Qing dynasty and the Republic of China. The data visualization method with integrated automation framework and parsing tools is helpful to analyze the subdivision characteristics of ancient TCM literatures，which is convenient，efficient and innovative，in the expectation to provide a classic reference for contemporary TCM studies.Keywords：traditional Chinese medicine oncology;automation framework;visualization analysis;Selenium;Tableau- 10
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20
Data Mining
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Considerations on Relevant Technical Requirements for Listing Application of Over-the-counter Traditional Chinese Medicine
Abstract：In this paper， a comparative analysis is carried out on the policy of listed drugs in Australia， the policy of over-the-counter drugs in Japan， the policy related to the conversion of Chinese patent medicines to over-the-counter drugs， and the policy related to health food. The focus is on one of the possible situations for the registration of over-the-counter traditional Chinese medicines （TCMs）， namely new prescription-composed over-the-counter TCMs. This paper discussed separately from the three parts of the scope of Chinese medicinal materials in the prescription medicines， the scope of indications， and the technical requirements， in order to provide references for the technical requirements related to the registration of over-the-counter TCMs. Recommendations on the marketing and registration of new prescription-composed over-the-counter TCMs：①It is recommended to formulate a list of medicinal materials for the use of Chinese herbal medicines， and consider including raw materials of health food. On this basis， a batch of safe Chinese medicinal materials/decoction pieces was added. And consider dynamic supervision， such as allowing the addition or recall of Chinese medicinal materials/decoction pieces in the list of medicinal materials. ②The scope of indications is recommended to consider the scope of indications for the conversion of Chinese patent medicines to over-the-counter TCMs in China， and the selection of medium-risk indications can reflect the characteristics and advantages of TCM treatment. ③Efficacy evaluation needs to provide high-quality scientific evidence， including clinical research data， and consider relaxing the requirements for non-clinical pharmacodynamic trials.Keywords：traditional Chinese medicine;over-the-counter drugs;registered drugs;drug policy;Chinese patent medicine;health food- 13
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Overview of Compilation and Research of
Lao Herbal Pharmacopoeia Abstract：In order to promote the standardization of traditional medicines in Laos， China and Laos jointly formed a census team to conduct resource survey， market survey， species identification and others of medicinal plants in Laos. According to the principles of nationality， tradition， effectiveness and commonness， 160 medicinal materials and 40 prescriptions were selected and collected into Lao Herbal Pharmacopoeia after recommendation， examination of experts and review by the established expert committee. Moreover， quality standards of traditional medicine and scientific and clear translation methods were formulated in line with the national conditions of Laos， and the contents were finally compiled according to the 2010 edition of Chinese Pharmacopoeia. The promulgation and implementation of Lao Herbal Pharmacopoeia is a successful example of cooperation in the field of health care between China and Laos， which is conducive to promoting mutually beneficial cooperation between China and Association of Southeast Asian Nations （ASEAN） countries in the field of traditional medicine， and making traditional medicine play a greater role in the medical and health services of ASEAN countries.Keywords：Lao Herbal Pharmacopoeia;traditional medicine;ethnic medicine;standardization;quality standards;Chinese Pharmacopoeia- 3
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20
Pharmacy Administration
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Analysis on Historical Evolution of Steaming Methods of Traditional Chinese Medicine Enhanced Publication
Abstract：Steaming is a traditional processing method of traditional Chinese medicine （TCM）. In this paper， taking the Collection of Processing Methods of TCM （Ancient Times） as a clue and checking the original herb books， the historical evolution of TCM steaming was sorted out and analyzed from four aspects， including steaming method， steaming variety， quality control method of steaming process， and steaming purpose. The results showed that the steaming method was originated from the Spring and Autumn period and the Warring States period. Afterwards， a total of 56 steaming methods were recorded. The most steamed varieties recorded in Song dynasty were 104， and the most newly added varieties in Song dynasty were 90. The steamed varieties recorded in the processing specifications of southern provinces and cities were higher than those of northern provinces and cities， including 43 in Guangdong province. The quality control of steaming process in Tang dynasty included steaming time， steaming times， softening by steaming， etc. In the Song dynasty， the steamed until aroma and sweet and steaming rotten were increased. In the Ming dynasty， the poisonous drugs steamed until no numbness of tongue and nontoxic was increased， and in the Qing dynasty， steaming and moistening was added. The main purposes of steaming in the past dynasties were recorded as enhancing the tonic effect， moderating the medicinal properties， reducing side effects， etc. In modern times， the purposes of preserving medicinal effects and facilitating storage were increased. From the perspective of the historical process of steam development， the Spring and Autumn period and the Warring States period to the Han dynasty were the embryonic period of steam development， the Southern and Northern dynasties， Tang and Song dynasties were the rapid periods of steam development， and the Ming and Qing dynasties were the prosperous periods of steam development. This paper can provide reference for the research and development of steaming technology.Keywords：steaming method;processed products;quality control;historical evolution;herbal textual- 7
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Progress on Molecular Mechanism of Curcumin and Its Nano-preparation Against Liver Cancer
Abstract：There are certain limitations in the application of liver transplantation， resection and radiofrequency ablation for liver cancer. Therefore，specific and selective new drugs are needed to provide better treatment. Curcumin is a hydrophobic polyphenol with a wide range of activities，such as anti-inflammatory，antibacterial，anti-oxidant and anti-tumor properties. Its nano-preparation has stronger growth inhibition and pro-apoptosis effects on tumor cells. Literature retrieval found that curcumin's anti-liver cancer molecular mechanisms include inhibiting cell proliferation by regulating the expressions of relevant miR，glyoxalase 1（GLO1），CD133 and vascular endothelial growth factor （VEGF），inhibiting signal transducer and activator of transcription （STAT3） and YAP expression to induce cell apoptosis，regulating the heat shock protein 70 （HSP70）-Toll-like receptor 4 （TLR4） signaling pathway，Wnt/β-catenin and transforming growth factor（TGF）/epithelial-mesenchymal transition（EMT） pathways，nuclear factor-κB （NF-κB） signaling pathway and nuclear factor E2-related factor 2（Nrf2）/ Kelch-like ECH-related protein 1（Keap1） signaling pathway，inhibiting p38 mitogen-activated protein kinase （MAPK） phosphorylation，to reduce Lin28B expression，regulating phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and inhibiting G protein-coupled receptors （GPR81）/hydroxycarboxylic acid receptor-1 （HCAR-1） expression to reverse transformation therapy resistance. Curcumin nano-preparation mainly includes polymer micelles，liposomes，loaded microbubbles，nanocapsules and nanoparticles. Curcumin is mainly delivered to liver cancer cells to rapidly release the drug，enhance the anti-liver cancer effect and reduce toxic and side effects in normal liver cells. The mechanisms include activation of DR5/Caspase-mediated exogenous apoptosis pathway and VEGF/VEGF receptors （VEGFRs） signaling pathway，loss of mitochondrial membrane potential and increase of intracellular reactive oxygen species （ROS）. This paper summarizes the molecular mechanism of curcumin and its nano-preparation against liver cancer，in order to further define the molecular mechanism of liver cancer and provide a new reference for its clinical diagnosis and treatment.Keywords：curcumin;nano-preparation;liver cancer;molecular mechanism- 12
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Research Progress on Anti-tumor Mechanism of Formononetin
Abstract：Formononetin is a kind of plant isoflavones extracted from medicinal herbs such as Trifolium pratense，Astragalus membranaceus and Spatholobi Caulis have shown that formononetin has strong anti-tumor biological activity，and can be used as an anti-tumor drug in the treatment of various malignant tumors. Many studies so far have shown that formononetin can inhibit cell proliferation，induce cell apoptosis，inhibit cell migration and invasion，and induce cell cycle arrest on tumors through a variety of molecular mechanisms and pathways. These antitumor activities can be observed in cells of various tumors such as breast cancer，colorectal cancer，prostate cancer，bladder cancer and lung cancer in trials and animal models. Examples of these effects include triggering the generation of reactive oxygen species （ROS），regulating phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） and Mitogen-activated protein kinases（MAPK） signaling pathways，inhibiting the activation of tyrosine kinase（JAK1 and JAK2 ）and nonreceptor tyrosine kinase（c-Src），and regulating cytokeratin 19（CK19），matrix metalloproteinases（MMP），microRNA-21（miR-21），lamin A/C antibody（Lamin A/C），expression of Cyclin D1 and Cyclin E1. In addition， the anti-tumor effects of formononetin derivatives were reviewed in this paper. By modifying the chemical structure of formononetin，many related derivatives have been obtained. Experimental results have shown that some derivatives of formononetin have stronger anti-tumor activity and lower cytotoxicity，but the related molecular mechanism of action still needs to be explored further in-depth. In conclusion，formononetin and its derivatives may become potential anti-tumor drugs.Keywords：formononetin;anti-tumor;derivative;mechanism- 9
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Progress on Hypoglycemic Effect and Mechanism of
Momordica charantia Abstract：Momordica charantia has been a traditional Chinese medicine （TCM） and food since ancient times. The discussions on its nature， taste and efficacy in ancient books of TCM are almost the same. With a high nutritional value， M. charantia is rich in a variety of vitamins and minerals， and has been widely used in the production of a wide range of dietary supplements and functional foods. At the same time， M. charantia is one of the most deeply studied natural medicines in traditional alternative medicine， with a wide range of pharmacological effects， especially in the treatment of metabolic diseases. Clinical trials have confirmed that M. charantia has a hypoglycemic effect， and could reduce blood lipids and weight loss， so as to improve metabolism in a comprehensive manner. According to the study on the mechanism of M. charantia in the treatment of diabetes， M. charantia could reduce blood sugar by improving islet β-cell function， improving insulin resistance， inhibiting intestinal glucose absorption and resisting inflammation and oxidative stress. However， at present， there is a lack of unified standards for the hypoglycemic effects and various mechanisms of action of M. charantia， and the safety has not been fully confirmed. Further studies shall be conducted to investigate the hypoglycemic effect and mechanisms of M. charantia， explore active components of M. charantia， define the pharmacodynamics material basis， extract monomer compounds with a clear structure and confirm its effectiveness and safety， which is helpful to develop and utilize the homologous value of medicine and food of M. charantia and further apply it in clinic. The application of the hypoglycemic effect of M. charantia in clinic has important economic benefits and a social significance.Keywords：Momordica charantia;diabetes;islet β-cell function;insulin resistance;inflammation;oxidative stress- 19
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Research Progress of Xinglou Chengqi Decoction in Treatment of Stroke with Heat-phlegm and Sthenic-Fu Syndrome Enhanced Publication
Abstract：Stroke is a destructive cerebrovascular event caused by the interruption of cerebral blood flow caused by the blockage or rupture of cerebral vessels， which is easy to cause physical disability and multiple functional injuries. The mortality rate of stroke patients in China occupies the first place in the world. How to effectively treat stroke is one of the urgent health problems to be solved. In the clinic， academician WANG Yong-yan observed that 60% of stroke patients with heat-phlegm and sthenic-Fu syndrome. Most of the patients with heat-phlegm and sthenic-Fu syndrome are characterized by stagnation of stool， bad breath and dry pharynx， and so on， After clinical practice， Xinglou Chengqi decoction （XLCQD） was established to treat stroke patients with heat-phlegm and sthenic-Fu syndrome. XLCQD is one of the representative prescriptions for removing phlegm to relax bowels， which is composed of Rhei Radix et Rhizoma， Natrii Sulfas， Trichosanthis Fructus and Arisaema Cum Bile by the ratio of 5∶5∶15∶3. At present， the research on XLCQD is mainly focused on clinical observation and pharmacological mechanism， while the basic research of its pharmacodynamic substance is relatively weak. This paper intends to sort out the chemical composition and pharmacological mechanism of XLCQD， in order to provide the basis for the chemical component identification， drug target prediction and material basis screening of this compound in the later stage. In addition， through the case analysis of XLCQD and modified XLCQD in the treatment of stroke， its rules of clinical application were summarized， in order to provide reference for the clinical application of this compound.Keywords：Xinglou Chengqi decoction;material basis;pharmacological effect;clinical application;stroke;Da Chengqitang;heat-phlegm and sthenic-Fu syndrome- 40
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Research Progress of Polypeptides Against Prostate Cancer
Abstract：Prostate cancer is an epithelial malignant tumor that occurs in the prostate. It is the most common cancer among men in the world. Its mortality rate is second only to lung cancer， which has seriously affected men's healthy life. Prostate cancer is not easy to be detected in the early stage. Most patients are already in the advanced stage and metastasized when they are diagnosed. At this time， radical surgery is not suitable for treatment. Advanced prostate cancer is mainly treated with endocrine therapy， but after a median time of 14-30 months， the patient will develop hormone-resistant prostate cancer and enter the advanced stage. Advanced hormone-resistant prostate cancer is treated with radiotherapy and chemotherapy， which， however， are not ideal for treating advanced prostate cancer. They can also cause serious side effects such as frequent urination， dysuria， urinary incontinence， rectal bleeding， loss of libido， hot flashes， and impotence， as well as generate multi-drug resistance. Therefore， it′s urgent to find a safe， effective and low-toxic anti-tumor drug. With the deepening of the research on the pharmacological effects of peptides， it has been proved that peptides have important application value in anti-fatigue， anti-aging， anti-inflammatory， antibacterial and anti-tumor. The anti-tumor peptides have attracted extensive attention in the field of anti-tumor research due to their high specificity， high bioavailability， good stability， low toxicity， low molecular weight， and easy synthesis. Pharmacological experiments have shown that polypeptides exert their anti-tumor effect mainly by inducing cell apoptosis， causing cell cycle arrest， inhibiting angiogenesis， and regulating immune function. This article summarized the related literature of peptides in recent years， the sources of peptides， the mechanisms and applications of peptides against prostate cancer for experimental research and clinical reference.Keywords：anti-tumor peptides;prostate cancer;mechanism;research progress- 6
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Research Progress of Intervention in Autoimmune Thyroid Diseases Based on Th17/ Treg Signal Axis with Traditional Chinese Medicine
Abstract：Autoimmune thyroid disease （AITD） is a complex organ-specific autoimmune disease， associated with many factors such as genetic susceptibility， environmental factors， immune system disorders， and intestinal microbiota imbalance， which seriously affect the quality of life. At present， oral medicine， iodine 131 treatment and surgical treatment are mainly adopted in clinical parctice of western medicine. Although they can exert a certain curative effect， they still have surgical risks and side effect. Modern research shows that， traditional Chinese medicine（TCM） has the characteristics of stable curative effect， multi-targeted regulation and less side effect. It has definite efficacy and unique advantages in the prevention and treatment of AITD. Helper T lymphocyte cell 17 （Th17） mediate inflammation to induce immune promotion， while regulatory T lymphocyte cell （Treg） mediate immunosuppression， Th17 and Treg cooperate to maintain the balance of the immune microenvironment. During AITD progress， Inflammatory Th17 can be high， and the levels of mediated immunosuppressive Treg are relatively decreased. The restoration of balance between the two plays a key role in the inflammatory and immune processes of AITD. In recent years， based on Th17/Treg cell axis， a large number of clinical and experimental studies on the intervention of TCM on Th17/Treg balance in AITD have been carried out in the field of TCM， and some results have been achieved. Studies have shown that intervention in the Th17/Treg signaling axis is an important mechanism for the treatment of autoimmune thyroid diseases. This paper summarizes and analyzes the previous studies on the intervention effect of Chinese medicine monomer， Chinese medicine composition and Chinese medicine compound on Th17/Treg cell axis in AITD， mainly from the aspects of intervention related inflammatory factor secretion， regulation of antibody titer and the expression of related genes of related genes. These studies will help people to understand the mechanism of TCM in interfering with the Th17/Treg balance in AITD more accurately and comprehensively， and provide references for the rational application of TCM in the prevention and treatment of autoimmune thyroid diseases in clinical practice.Keywords：autoimmune thyroid disease;helper T lymphocyte cell 17（Th17）/regulatory T lymphocyte cell （Treg）;traditional Chinese medicine;signaling pathway- 31
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20 -
Analysis on Role of mTORC1/4E-BP1 Axis in Idiopathic Pulmonary Fibrosis and Research Progress of Bupleuri Radix on Its Intervention
Abstract：Idiopathic pulmonary fibrosis （IPF） is a common， lethal interstitial lung disease characterized by airway remodeling， inflammation， alveolar destruction， and fibrosis. The mammalian target of rapamycin complex 1/4E binding protein 1 （mTORC1/4E-BP1） axis is closely related to the expression of collagen by fibroblasts， and its role in pulmonary fibrosis remains to be further elucidated. Traditional Chinese medicine （TCM） has shown promising efficacy in improving the lung function， exercise capacity， and quality of life in patients with IPF. The theory of "same treatment for different diseases" provides a TCM theoretical basis for the treatment of pulmonary fibrosis with Bupleuri Radix， while the research in western medicine has preliminarily shown that both the formulation and single herb as well as the active ingredients of Bupleuri Radix have good therapeutic effects on pulmonary fibrosis. Therefore， this review will elaborate on the role of the mTORC1/4E-BP1 axis in the pathomechanism of IPF， as well as the research results of the active components of Bupleuri Radix on the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin protein（PI3K/AKT/mTOR） pathway， so as to provide a reference for the treatment and drug development of IPF.Keywords：mammalian target of rapamycin complex 1（mTORC1）;4E binding protein 1（4E-BP1）;idiopathic pulmonary fibrosis;Bupleuri Radix- 6
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<HTML><CITATION> <Bulk Citation>Published：2021-04-20
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