最新刊期
卷 29 ， 期 5 ， 2023
- 摘要：ObjectiveTo systematically evaluate the safety of Chinese medicines combined with Tripterygium wilfordii polyglycoside tablets/Tripterygium wilfordii tablets （TWPT/TWT） in the treatment of rheumatoid arthritis （RA）， and to explore the network regulatory mechanisms of enhancing efficacy and reducing toxicity of commonly used combination regimes.MethodThe literature involving the adverse reactions of TWPT/TWT in treating RA was searched and collected from three Chinese databases （CNKI， Wanfang Data， VIP） and three English databases （PubMed， Cochrane Library， Embase） from the inception of the databases to July 2021. All studies were assessed by the Cochrane risk of bias tool， and the data were extracted and analyzed by Stata 15.0. Furthermore， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine 2.0 （TCMIP v2.0，http：//www.tcmip.cn/） was used to construct a "drug target-symptom gene of efficacy and toxicity" interaction network， to explore the underlying network regulatory mechanisms of enhancing efficacy and reducing toxicity of common T. wilfordii preparation combinations.ResultA total of 2 132 articles on Chinese medicines combined with TWPT/TWT in the treatment of RA were retrieved， and 18 of them were finally included. The systematic review showed that the adverse reactions of TWPT/TWT against RA mainly occurred in the digestive system， blood system， and reproductive system， of which digestive system had the highest incidence of damages. However， the combination with Chinese medicines effectively alleviated the adverse reactions caused by TWPT/TWT ［RR （95% CI）=0.45 （0.30， 0.66）， P<0.01］. In addition， the subgroup analysis indicated that the age of RA patients， course of disease， combination regimen， medication dosage and duration of treatment all affected the occurrence of adverse reactions of TWPT/TWT. It was found in clinical studies that total glucosides of paeony （TGP） and TWPT/TWT was most widely combined， and the effect of TGP in reducing TWPT/TWT-induced hepatotoxicity was also more significant than that of other Chinese medicines. Moreover， taking this combination regime as an example， this paper explored the "efficacy-toxicity" association mechanisms of TGP-TWPT/TWT against RA. The "drug target-symptom gene of efficacy and toxicity" interaction network revealed that the core network targets of TGP-TWPT/TWT enhanced efficacy and reduced toxicity mainly through regulating immunity-inflammation-related pathways， metabolic pathways and cell signal transduction. Especially， interleukin-4 （IL-4） and interleukin-13 （IL-13）， which were involved in the "immunity-inflammation" module， were the common targets of TGP-TWPT/TWT to enhance efficacy and reduce toxicity. The endogenous sterols， bile acids and bile salts， insulin secretion and other metabolic pathways in the "body metabolism" module were closely associated with the mechanisms of TWPT/TWT inducing hepatotoxicity and TGP reducing hepatotoxicity. While cell function regulation pathways， such as stem cell factor （SCF）/tyrosine kinase receptor （KIT） signaling pathway and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）signaling pathway were involved in both anti-RA effects and hepatotoxicity of TWPT/TWT.ConclusionClinical application of suitable Chinese medicines combined with TWPT/TWT in the treatment of RA can effectively improve the rheumatism and reduce the adverse reactions of TWPT/TWT， and TGP-TWPT/TWT has the most significant toxicity-reducing effect. Further biological network-based investigation indicates that the toxicity-reducing mechanism of TGP-TWPT/TWT may be related to the regulation of interleukin signaling pathway and bile acid metabolism pathway， and the synergistic efficacy-enhancing effect of the combination may be achieved by acting on interleukin signaling pathway and cell function regulation pathway.关键词：Tripterygium wilfordii preparations;combination with Chinese medicines;clinical rational use of drugs;systematic reviews;network pharmacology
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发布时间：2023-02-07 - 摘要：ObjectiveTo observe the effect of Cuscutae Semen total flavonoids combined with Tripterygium wilfordii polyglycoside tablets （TWPT） on ovarian germline stem cells of female physiological mice through neurogenic locus notch homolog （Notch） signaling pathway.MethodSixty female Kunming mice （5 weeks old） were randomly divided into normal group， Tripterygium wilfordii polyglycoside tablets low-， high-dose groups （13.65 mg·kg-1·d-1 and 27.3 mg·kg-1·d-1， 1 and 2 times clinical equivalent dose）， Cuscutae Semen total flavonoids low- and high-dose groups （150 mg·kg-1·d-1 and 300 mg·kg-1·d-1）， and combination group （13.65 mg·kg-1·d-1 TWPT and 150 mg·kg-1·d-1 Cuscutae Semen total flavonoids）， with 10 in each group. After 3 weeks of continuous administration， the uterus/brain and ovarian/brain indexes were calculated， and the pathological changes of ovarian tissue were observed under light microscope. The content of estradiol in serum was determined by enzyme linked immunosorbent assay （ELISA）. Immunofluorescence assay was performed to observe the expressions of germline stem cell markers in ovarian epithelium， including mouse vasa homologue （Mvh）， octamer-binding transcription factor 4 （Oct4）， tyrosine-protein kinase receptor （c-kit）， Nanog， Notch signaling pathway molecules， neurogenic locus notch homolog protein 1 （Notch1）， hes family BHLH transcription factor 1（Hes1）， and jagged canonical Notch ligand 1 （JAG1）.ResultCompared with the normal group， low and high doses of TWPT had no significant effect on the uterus/brain and ovary/brain indexes and the uterus and ovary morphologies of mice， while only the number of atretic follicles was increased （P<0.01）. The expressions of ovarian germline stem cell markers and Notch signaling pathway molecules had a decreasing trend in TWPT low-dose group， while the expressions of Mvh， c-kit， and Nanog were down-regulated （P<0.05， P<0.01） and the expressions of Notch1 and Hes1 were also reduced （P<0.01） in TWPT high-dose group. However， the above indexes were increased in Cuscutae Semen total flavonoids low-dose group （P<0.05， P<0.01）. Compared with the low does of TWPT group， the combination group had a decrease in the increased number of atretic follicles （P<0.01）， an improvement in the down-regulated expressions of Mvh and Nanog （P<0.01）， and an increase in the expressions of Notch1 and Hes1 （P<0.05， P<0.01）.ConclusionOvarian germline stem cells are the source target of the reproductive toxicity of TWPT. Cuscutae Semen total flavonoids participate in the regulation of the germline stem cell pathways to alleviate the reproductive toxicity caused by TWPT， and its mechanism of action may be related to the Notch signaling pathway.关键词：Tripterygium wilfordii polyglycoside tablets（TWPT）;Cuscutae Semen total flavonoids;combination;ovarian germline stem cells;neurogenic locus notch homolog protein （Notch） signaling pathway
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发布时间：2023-02-07 - 摘要：ObjectiveTo explore the underlying mechanism of Tripterygium wilfordii polyglycoside tablets （TWPT） in the prevention and treatment of kidney injury in diabetic nephropathy （DN） through the nuclear factor of activated T-cells 2（NFAT2）/cyclooxygenase-2（COX-2） pathway.MethodForty-two male SD rats of SPF grade were selected and randomly divided into a normal group （n=8） and an experimental group （n=34） after one week of adaptive feeding. The rats in the normal group were fed conventionally. The DN model was established in rats of the experimental group by intraperitoneal injection of streptozotocin （STZ） following one week of feeding on a high-fat and high-glucose diet. After the death and failure cases during modeling were eliminated， the remaining 24 model rats were randomly divided into model group， valsartan （8.33 mg·kg-1·d-1） group， and TWPT （5 mg·kg-1·d-1） group. Rats in normal group and model group were given equal amounts of normal saline by gavage. After six weeks， body weight was measured and urine samples were collected. Blood samples were collected from the abdominal aorta， and then the rats were sacrificed for sampling. Biochemical indicators， such as serum blood urea nitrogen （BUN）， serum creatinine （SCr）， alanine aminotransferase （ALT）， blood lipid， blood glucose， and 24-hour urine total protein （24 h UTP）， were determined. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathology of the kidney. Enzyme-linked immunosorbent assay （ELISA） was used to detect NFAT2 and COX-2 expression levels in the serum. Western blot and Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）were adopted to detect NFAT2， COX-2 protein and mRNA expression in kidney tissues， respectively.ResultCompared with the normal group， the model group showed elevated 24 h UTP， BUN， SCr， CHO， TG， and FBG， increased serum NFAT2 and COX-2 production and expression （P<0.01）， and elevated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues （P<0.01）. In addition， the pathology of the kidney showed enlarged glomeruli， mild proliferation of mesangial cells， and widened mesangial stroma. Compared with the model group， the TWPT group showed decreased 24 h UTP， BUN， SCr， CHO， TG， and FBG （P<0.05，P<0.01）， basically normal glomerular morphology， decreased expression of serum NFAT2 and COX-2 （P<0.01）， and down-regulated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues （P<0.01）.ConclusionTWPT can alleviate 24 h UTP in DN model rats， protect renal function， and improve renal pathology， and its mechanism of action may be related to the down-regulation of NFAT2/COX-2 expression in the serum and kidney tissues.关键词：Tripterygium wilfordii polyglycoside tablets;diabetic nephropathy;nuclear factor of activated T-cells 2（NFAT2）/cyclooxygenase-2（COX-2） pathway;experimental study
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发布时间：2023-02-07 - 摘要：ObjectiveTo investigate the protective effect of cytochrome P4502D6 （CYP2D6） and cytochrome P4503A4 （CYP3A4）， key enzymes of drug metabolism in liver， on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma （WEOGRR）.MethodHealthy male Kunming mice were divided into normal group， model group， WEOGRR low-， medium- and high-dose groups （5， 10， 15 g·kg-1·d-1） and positive drug group （diammonium glycyrrhizinate， 75 mg·kg-1·d-1）， with 10 in each group. One week after preventive administration， acute liver injury model was induced by single intragastric administration of 270 mg·kg-1 Tripterygium Glycosides tablets， and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining. Serum liver function indexes including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptadase （γ-GT）， alkaline phosphatase （ALP）， and total bilirubin （TBIL） as well as the levels of oxidative stress indexes including malondialdehyde （MDA） and superoxide dismutase （SOD） in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4， respectively.ResultCompared with normal group， model group had significant hepatocyte swelling and inflammatory cell infiltration （P<0.01）， increased AST， ALT， γ-GT， ALP and TBIL （P<0.05）， elevated MDA and decreased SOD （P<0.01） as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 （P<0.05）. Compared with the model group， the normal group had intact liver structure without obvious abnormality， and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration （P<0.01）， reduced AST， ALT， γ-GT， ALP and TBIL （P<0.01）， lowered MDA and increased SOD （P<0.01） as well as up-regulated expression levels of CYP2D6 and CYP3A4 （P<0.01）.ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST， ALT， γ-GT， ALP and TBIL in serum， inhibiting MDA and increasing the activity of SOD in liver cells， and enhancing the activities of CYP2D6 and CYP3A4， thus accelerating the metabolism of toxic substances.关键词：Tripterygium wilfordii polyglycoside tablets;liver injury;Glycyrrhizae Radix et Rhizoma;cytochrome P450
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发布时间：2023-02-07 - 摘要：ObjectiveTo investigate the effect of Xinfeng capsules on immunoinflammatory indicators in patients with rheumatoid arthritis （RA） due to spleen deficiency and dampness exuberance.MethodA total of 102 patients were randomly divided into control group and observation group according to the random number table method， with 51 cases in each group. All patients were treated with methotrexate tablets， while those in the observation group received additional Xinfeng capsules. The course of treatment in both groups was 12 weeks. The 28-joint disease activity score （DAS28）， visual analogue scale （VAS） scores， morning stiffness time， erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide （anti-CCP） antibody， vascular endothelial growth factor （VEGF）， and serum amyloid A （SAA） of the two groups before and after treatment were compared. The efficacy and incidence of adverse events were compared between the two groups. The Apriori association rule model and random walk model were constructed to evaluate the effect of Xinfeng capsules in improving hs-CRP， ESR， RF， SAA， VEGF， and anti-CCP.ResultThere were no dropouts in this study. There was no statistical difference in the indicators between the two groups before treatment. After 12 weeks of treatment， the total effective rate in the observation group was 90.19% （46/51）， which was higher than 74.51% （38/51） in the control group （χ2＝4.320，P<0.05）. DAS28， VAS score， and morning stiffness time in the observation group were improved compared with those in the control group （P<0.05）. Apriori association rule model results showed that the application of Xinfeng capsules in the observation group had a strong correlation with the reduction of RF， ESR， hs-CRP， SAA， and VEGF. The results of the random walk model showed that the improvement coefficients of hs-CRP， ESR， RF， SAA， and VEGF in the observation group were all better than those of the control group， and the improvement coefficient of anti-CCP in the control group was better than that of the observation group. The improvement degree of hs-CRP， ESR， RF， SAA， and VEGF in the observation group was superior to that of the control group （P<0.05）. The incidence of adverse reactions in the observation group was lower than in the control group （χ2＝4.057，P<0.05）.ConclusionOn the basis of the treatment with methotrexate tablets， Xinfeng capsules can effectively improve the immunoinflammatory level in RA due to spleen deficiency and dampness exuberance and reduce the incidence of adverse reactions.关键词：Xinfeng capsules;rheumatoid arthritis;immunoinflammation;spleen deficiency and dampness exuberance syndrome
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发布时间：2023-02-07 - 摘要：ObjectiveTo evaluate the effect of Tripterygium wilfordii polyglycoside tablets （TWPT） combined with conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） including methotrexate （MTX） and/or leflunomide （LEF） on autoantibodies in rheumatoid arthritis （RA） patients.MethodPubMed， EMBASE， Web of Science， Cochrane Library， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched for randomized controlled trials （RCTs） of TWPT combined with MTX and/or LEF in the treatment of RA patients from database inception to December 1， 2021. Primary outcome indicators included rheumatoid factor （RF） and anti-citrullinated protein antibody （ACPA）， and secondary outcome indicators included immunoglobulin （IgA， IgG， and IgM） and adverse drug events （ADE）.ResultThirty-one RCTs， involving 2 643 adult patients， were included， including 20 RCTs of TWPT combined with MTX， 10 of TWPT combined with LEF， and one of TWPT combined with MTX and TWPT. The follow-up time ranged from two weeks to 13 months. Compared with csDMARDs alone， TWPT combined with other drugs significantly improved serum RF of RA patients ［SMD=-2.45， 95% CI ［-2.97， -1.93］， P<0.000 01］， anti-CCP ［SMD=-1.41， 95% CI （-2.35， -0.48）， P=0.003］， IgM ［SMD=-1.90， 95% CI （-3.03， -0.76）， P=0.001］， and IgA ［SMD=-1.18， 95% CI （-2.23， -0.12）， P=0.03］. There were no significant effects on IgG ［SMD=-1.02， 95% CI （-2.04， 0.01）， P=0.05］ and ADE ［RR=0.87， 95% CI （0.66， 1.15）， P=0.32］.ConclusionThe results of this study show that compared with csDMARDs alone， TWPT combined with csDMARDs can effectively improve the levels of autoantibodies in RA patients without increasing the incidence of ADE. However， due to the limited quality and quantity of the included RCTs， the relevant conclusions are only used as a reference for the clinical diagnosis and treatment of RA， and more high-quality studies are still needed to further confirm their efficacy.关键词：Tripterygium wilfordii polyglycoside tablets;rheumatoid arthritis;autoantibodies;Meta-analysis
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发布时间：2023-02-07 - 摘要：ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury.MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis.ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction.ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.关键词：Tripterygium wilfordii polyglycoside tablets;rheumatoid arthritis;drug-induced liver injury;multi-omics integration;"efficacy-toxicity" association network
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发布时间：2023-02-07 - 摘要：ObjectiveTo observe the effect of Shenling Baizhusan on the intervention of the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway by regulating ferroptosis in rats with alcoholic liver injury.MethodForty SD rats were randomly divided into model group， polyene phosphatidylcholine group， and high， medium， and low-dose Shenling Baizhusan groups， with 8 rats in each group. Another 8 SD rats were taken as blank group. The model group， polyene phosphatidylcholine group， high， medium， and low-dose Shenling Baizhusan groups were given 10 mL·kg-1 liquor by gavage for modeling， and the blank group was given equal volume of distilled water by gavage. After 4 h of daily alcoholic administration， 143.64 mg·kg-1 of polyene phosphatidylcholine group was given to the polyene phosphatidylcholine group， 15， 7.5， 3.75 mg·kg-1 of Shenling Baizhusan were given to Shenling Baizhusan high， medium， and low-dose groups， respectively， and the blank group and the model group were given equal volume of distilled water. The gavage lasted for 6 weeks. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， glutamyl transpeptidase （GGT）， total cholesterol （TC）， and triglyceride （TG） were detected by automatic biochemical analyzer. The levels of tumor necrosis factor-α （TNF-α） and interleukin-β （IL-β） were detected by the enzyme-linked immunosorbent assay （ELISA）. The levels of lipopolysaccharide （LPS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）， and Fe+ were detected by biochemical assay. The pathological changes in the liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The mRNA expression levels of Nrf2， heme oxygenase-1 （HO-1）， glutathione peroxidase 4 （GPX4）， ferritin heavy polypeptide 1 （FTH1）， and nuclear factor-κB （NF-κB） were detected by Real-time polymerase chain reaction （Real-time PCR）. The protein expression levels of Nrf2， HO-1， GPX4， FTH1， p65， and phosphorylation （p）-p65 were detected by Western blot.ResultAs compared with the blank group， the levels of liver function （ALT， AST， and GGT） and blood lipids （TC and TG） in the model group were significantly increased （P<0.05）. The liver showed obvious steatosis， with a large number of fat deposition， the oxidative stress and inflammatory factors were significantly increased （P<0.05）， and the level of Fe+ was significantly increased in model group （P<0.05）. The protein expression levels of Nrf2， HO-1， GPX4， and FTH1 was significantly down-regulated （P<0.05）， and those of p65 and p-p65 was significantly up-regulated in the model group （P<0.05）. The mRNA expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly down-regulated （P<0.05）， and the mRNA expression level of NF-κB was significantly up-regulated （P<0.05）. As compared with the model group， the levels of liver function （ALT， AST， and GGT） and blood lipids （TC and TG） in the high-dose and medium-dose Shenling Baizhusan groups were significantly decreased （P<0.05）， liver steatosis was significantly improved， fat deposition was significantly reduced， oxidative stress and inflammatory factors were significantly decreased （P<0.05 ）， and Fe+ level was significantly decreased （P<0.05）. In the high-dose and medium-dose Shenling Baizhusan， the protein expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly up-regulated （P<0.05）， and those of p65， p-p65 were significantly down-regulated （P<0.05）. The mRNA expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly up-regulated （P<0.05）， and the mRNA expression level of NF-κB was significantly down-regulated （P<0.05）.ConclusionShenling Baizhusan can effectively reduce liver injury in rats with ALD， regulate steatosis and fat deposition， and play an antioxidant and anti-inflammatory role in the liver. Its mechanism may be related to the inhibition of ferroptosis in hepatocytes by up-regulating the Nrf2 signaling pathway to improve oxidative stress关键词：Shenling Baizhusan;alcoholic liver injury;nuclear factor erythroid 2-related factor 2 （Nrf2）;oxidative stress;ferroptosis
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发布时间：2023-02-07 - 摘要：ObjectiveTo explore the effects of Baihu Jia Renshen Tang （BHRS） on the related molecules on the phosphatidylinositol-3-kinase/protein kinase B（PI3K/Akt）signaling pathway in the liver of MKR diabetic model mice.MethodThirty 6-week-old MKR mice were selected and fed on a high-fat diet for four weeks，followed by intraperitoneal injection of streptozotocin（STZ）for the diabetes model establishment. The model was properly induced in the case of the fasting blood glucose （FBG） of ≥11.1 mmol·L-1. After modeling，the mice were randomly divided into a model group，a BHRS group （12.09 g·kg-1·d-1），and a metformin group （0.065 g·kg-1·d-1），with 10 mice in each group. Ten FVB mice were assigned to the control group. The mice in the groups with drug intervention were continuously administered correspondingly for 28 days. After administration，the mice were sacrificed，followed by the oral glucose tolerance test （OGTT） and FBG detection. Serum very low-density lipoprotein（VLDL）content was determined by semi-quantitative enzyme-linked immunosorbent assay （ELISA）. Four indexes related to blood lipid were determined by the biochemistry analyzer. Liver tissues were subjected to pathological examination by hematoxylin-eosin（HE）staining. Western blot was used to detect the protein expression of PI3K，Akt，phosphorylated（p）-PI3K，p-Akt，forkhead box protein O1 （FoxO1），insulin receptor（InsR），and insulin receptor substrate-2（IRS-2） in liver tissues of mice. Real-time polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression of PI3K，Akt，FoxO1，InsR，and IRS-2 in liver tissues of mice.ResultCompared with the control group，the model group showed poor general conditions，abnormal glucose tolerance （P<0.05），increased FBG （P<0.01），abnormal blood lipid metabolism，increased serum total cholesterol （TC），triglyceride（TG），low-density lipoprotein cholesterol（LDL-C），and VLDL （P<0.05），decreased level of high-density lipoprotein cholesterol（HDL-C）（P<0.05），fatty degeneration and obvious pathological changes of liver cells，reduced protein expression of PI3K，Akt，p-PI3K/PI3K，p-Akt/Akt，IRS-2，and InsR in liver tissues（P<0.05），increased protein expression of FoxO1（P<0.05），decreased mRNA expression of PI3K，Akt，IRS-2，and InsR in liver tissues （P<0.05），and increased FoxO1 mRNA expression（P<0.05）. Compared with the model group，the BHRS group showed improved general conditions and glucose and lipid metabolism （P<0.05），improved pathological state of liver cells，increased protein expression of PI3K，Akt，p-PI3K/PI3K，p-Akt/Akt，IRS-2，and InsR in liver tissues（P<0.05），decreased protein expression of FoxO1（P<0.05），increased mRNA expression of PI3K，Akt，IRS-2，and InsR in liver tissues （P<0.05），and reduced FoxO1 mRNA expression（P<0.05）.ConclusionBHRS can effectively reduce blood glucose，regulate blood lipid metabolism，and improve the pathological state of the liver in MKR diabetic mice，and its mechanism of action may be related to the regulation of the activity of molecules on the PI3K/Akt signaling pathway.关键词：Baihu Jia Renshen Tang;phosphatidylinositol-3-kinase/protein kinase B（PI3K/Akt）signaling pathway;type 2 diabetes;glucose and lipid metabolism
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发布时间：2023-02-07 - 摘要：ObjectiveTo explore the effect of Babaodan （BBD） on the NOD-like receptor pyrin domain containing 3/cysteine aspartate-specific protease-3 （NLRP3/Caspase-1） pathway proteins in mice with acetaminophen （APAP）-induced acute liver injury.MethodC57BL/6 mice were randomly grouped， and BBD （75， 150， 300 mg·kg-1， ig） was administered twice a day for three days. After 2 hours of the last administration， the mice were treated with APAP （400 mg·kg-1， ip）， and the eyeballs were removed to collect blood after 14 hours. Then they were sacrificed by cervical dislocation for sample collection. Hematoxylin-eosin （HE） staining was used to observe the morphological changes of liver tissue cells， and biochemical methods were used to detect the activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， superoxide dismutase （SOD）， malondialdehyde （MDA） and myeloperoxidase （MPO） in serum of mice in each group. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was performed to determine the mRNA expression of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-6， and Western blot was performed to determine the protein expression of cyclooxygenase-2 （COX-2）， inducible nitric oxide synthase （iNOS）， NLRP3， Caspase-1 and IL-18 in the liver of mice.ResultCompared with the conditions in normal group， the hepatic lobule structure of mice in the model group was partially destroyed， and the hepatic sinusoids were dilated. And the expression levels of ALT and AST in serum， the protein levels of NLRP3， Caspase-1， iNOS， IL-18 and COX-2 and the mRNA levels of IL-1β， IL-6 and TNF-α were increased （P<0.05， P<0.01）. Compared with the model group， the administration groups had improvement in liver cell rupture and hepatic sinusoidal compression， and a dose-dependent decrease in the levels of ALT and AST in serum as well as the protein levels of NLRP3， Caspase-1， iNOS， IL-18 and COX-2 and the the mRNA levels of IL-1β， IL-6 and TNF-α in liver tissue （P<0.05， P<0.01）.ConclusionBBD can reduce APAP-induced acute liver injury in mice. The mechanism may be related to anti-oxidative stress， inhibition of NLRP3/Caspase-1 pathway， and decreased expression levels of IL-1β， IL-18， TNF-α and IL-6.关键词：Babaodan;acute liver injury;inflammatory factors;NOD-like receptor pyrin domain containing 3 （NLRP3）;cysteine aspartate-specific protease-3 （Caspase-1）
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发布时间：2023-02-07 - 摘要：ObjectiveTo investigate the protective effect of Guiqi Baizhu prescription combined with oxaliplatin on the intestinal barrier of tumor-bearing mice with gastric cancer by regulating downstream aquaporin 3 （AQP3） and aquaporin 4 （AQP4） through the vasoactive intestinal peptide （VIP）/cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA） signaling pathway.MethodThe gastric cancer cell lines MFC with a density of 1×107/mL were prepared into cell suspension. The tumor-bearing mouse model of gastric cancer was established by inoculating 0.2 mL cell suspension under the right axilla of mice. After successful modeling， mice were randomly divided into 5 groups， namely， model group， oxaliplatin group （10 mg·kg-1）， and high， medium， and low-dose oxaliplatin + Guiqi Baizhu prescription groups （17.68， 8.84， 4.42 g·kg-1）， with 10 mice in each group， and the remaining 10 mice were set as a blank group. Mice in each group were treated with Chinese medicine， oxaliplatin， or normal saline by gavage or intraperitoneal injection for 14 d. The next day after the last dose， blood was taken from the eyeball to separate serum and take colonic samples. Hematoxylin-eosin （HE） staining was used to observe the changes in tissue morphology. The content of D-lactate acid （D-LA） and diamine oxidase （DAO） in the serum was determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of VIP， cAMP， PKA， AQP3， and AQP4 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively.ResultCompared with the blank group， the model group showed edema in the colonic submucosa， disordered arrangement of intestinal glands in the mucosal layer， loss of goblet cells， infiltration of inflammatory cells， and villus shedding. However， there were different degrees of improvement in each administration group. As compared with the blank group， the serum levels of DAO and D-LA in the model group were significantly increased （P<0.01）. As compared with the model group， the levels of DAO and D-LA in the high-dose oxaliplatin + Guiqi Baizhu prescription group and the level of D-LA in the medium-dose oxaliplatin + Guiqi Baizhu prescription group were decreased （P<0.05， P<0.01）. As compared with the oxaliplatin group， the levels of D-LA in the high and medium-dose oxaliplatin + Guiqi Baizhu prescription groups were decreased （P<0.05）， and the levels of DAO and D-LA in other administration groups were decreased as well， but the difference had no statistical significance. As compared with the blank group， the mRNA and protein expression levels of VIP， cAMP， PKA， AQP3， and AQP4 in the model group were significantly decreased （P<0.05， P<0.01）. As compared with the model group， the mRNA and protein expression levels of VIP， cAMP， PKA， AQP3， and AQP4 in each administration group were increased， and those in the high-dose oxaliplatin + Guiqi Baizhu prescription group were significantly increased （P<0.05， P<0.01）， while the protein expression level of cAMP in the medium-dose oxaliplatin + Guiqi Baizhu prescription group were increased （P<0.05）. As compared with the oxaliplatin group， the protein expression levels of cAMP in the high-dose oxaliplatin + Guiqi Baizhu prescription group were increased （P<0.05）， and the mRNA and protein expressions of these indexes in the other groups were also increased but the differences were not statistically significant.ConclusionGuiqi Baizhu prescription combined with oxaliplatin can regulate AQP3 and AQP4 through the VIP/cAMP/PKA signaling pathway to protect the intestinal barrier of tumor-bearing mice with gastric cancer.关键词：Guiqi Baizhu prescription;gastric cancer;intestinal barrier damage;vasoactive intestinal peptide （VIP）/cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA） signaling pathway;aquaporin 3 （AQP3）;AQP4
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发布时间：2023-02-07 - 摘要：ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism.MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot.ResultCompared with the blank group， 200 μmol·L-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）.ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.关键词：rutin;3T3-L1 preadipocytes;adipocyte browning;obesity;mitochondrial biogenesis
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发布时间：2023-02-07 - 摘要：ObjectiveTo investigate effect of astragaloside Ⅳ on the proliferation， migration， and invasion of colorectal cancer HCT116 cells and the underlying molecular mechanism.MethodColorectal cancer HCT116 cells were classified into blank group （DMSO） and low-dose （15.7 mg·L-1）， medium-dose （31.4 mg·L-1）， and high-dose （62.8 mg·L-1） astragaloside Ⅳ groups. After drug treatment， the morphological changes of HCT116 cells were observed under an inverted microscope. Cell viability was detected by cell counting kit-8 （CCK-8） assay， and the migration and invasion of cells were detected based on scratch assay and Transwell assay. The expression of cyclin-dependent kinase inhibitor （p21）， CyclinD1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the cells was examined by Western blot.ResultCompared with the blank group， cells in the three astragaloside Ⅳ groups demonstrated slow growth， low density， inconsistent morphology， nuclear shrinkage， degradation of cytoplasm， and high death rate. Moreover， cell viability decreased in a concentration-dependent manner in the astragaloside Ⅳ groups. Cell migration and invasion were inhibited （P<0.05， P<0.01）， and the inhibition rate was in positive correlation with the concentration of the astragaloside Ⅳ. The expression of pro-apoptotic protein Bax in low-dose， medium-dose and high-dose astragaloside Ⅳ groups increased gradually in a concentration-dependent manner， while the expression of p21， CyclinD1 and anti-apoptotic protein Bcl-2 decreased gradually in a concentration-dependent manner compared with those in the blank group （P<0.05， P<0.01）.ConclusionAstragaloside Ⅳ can suppress the proliferation， migration， and invasion of colorectal cancer HCT116 cells and promote the apoptosis， thus inhibiting the occurrence and development of colorectal cancer.关键词：astragaloside Ⅳ;colorectal cancer;proliferation;migration;invasion
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发布时间：2023-02-07 - 摘要：ObjectiveTo explore the clinical effect of Tiaoxin formula in the treatment of patients with coronary heart disease and anxiety/depression and its impact on serum levels of 5-hydroxytryptamine （5-HT）， β- thromboglobulin （β-TG） and myeloperoxidase （MPO）.MethodA total of 66 patients with coronary heart disease and anxiety/depression were randomly divided into the Tiaoxin formula group and Deanxit group， 33 cases in each group. Both groups were given fundamental western treatment for coronary heart disease. Additionally， the Deanxit group was treated with flupentixol and melitracen tablets and the Tiaoxin formula group was treated with Tiaoxin Formula. The treatment lasted 8 weeks. Before and after treatment， the changes of clinical efficacy， Patient Health Questionnaire （PHQ-9）， Generalized Anxiety Disorder （GAD-7） scale， Seattle Angina Questionnaire （SAQ）， heart rate variability， and serum 5-HT， β-TG and MPO levels， and incidence of adverse reactions in the two groups were observed.ResultThere was no significant difference in the baseline indexes of patients in the two groups， and thus the two groups were comparable. After treatment for 8 weeks， the total effective rate for traditional Chinese medicine （TCM） syndromes in the Tiaoxin Formula group was 87.88% （29/33） higher than 63.64% （21/33） in the Deanxit group （Z=-2.653， P<0.05）. Compared with those before treatment， the PHQ-9 and GAD-7 scores of the two groups were decreased at week 4 and 8 of treatment （P<0.05）， and there was no statistical difference between two groups. And the SAQ dimension scores of the two groups were increased at week 4 and 8 of treatment （P<0.05）. Compared with the Deanxit group， the Tiaoxin Formula group had elevation in two dimension scores： Physical limitation and angina stability （P<0.05）. Compared with the conditions before treatment， the serum 5-HT level in the two groups were increased， while the β-TG and MPO levels were lowered （P<0.05）， and there was no distinct difference between two groups. In addition， the standard deviation of normal-to-normal intervals （SDNN） and standard deviation of average normal-to-normal intervals （SDANN） of the heart rate variability in the Tiaoxin formula group were elevated after treatment （P<0.05）， which were more significant than those of the Deanxit group （P<0.05）. During the treatment period， the incidence of adverse drug reactions in the Tiaoxin formula group was lower than that in the Deanxit group （P<0.05）， and no adverse events were observed in the two groups.ConclusionTiaoxin formula was effective for the treatment of patients with coronary heart disease accompanied by anxiety and depression， which improved the clinical symptoms， increased serum 5-HT levels， and decreased serum β-TG and MPO levels， and had few adverse reactions and high safety for patients， showing a high clinical value.关键词：Tiaoxin formula;coronary heart disease;anxiety/depression;serum 5-hydroxytryptamine （5-HT）;serum β-thromboglobulin （β-TG）;serum myeloperoxidase （MPO）
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发布时间：2023-02-07 - 摘要：ObjectiveTo evaluate the efficacy and influencing factors of Biejiajianwan in the treatment of primary liver cancer based on real-world data of traditional Chinese medicine （TCM）.MethodClinical diagnosis and treatment data of patients with primary liver cancer admitted to five Grade-A tertiary hospitals in Henan Province from January 2015 to December 2020 were collected from the medical electronic database. The patients treated with Biejiajianwan for ≥30 days were assigned to the exposure group and those without treatment with Biejiajianwan or treated with Biejiajianwan for <30 days to the non-exposure group. The propensity score matching model was used to balance confounding factors between the two groups according to the 1∶1 genetic matching method. Kaplan-Meier method was used for survival analysis and survival curve plotting. Log-rank was used to test the difference in survival rate between the two groups. Univariate analysis of Biejiajianwan in the treatment of primary liver cancer was performed by Log-rank test combined with the Kaplan-Meier method. The factors with statistical significance （P<0.05） were combined with unbalanced factors by the propensity score matching model， and at the same time， clinical common sense and relevant prognostic factors by literature search were considered， which were subjected to multivariate analysis by Cox proportional hazards regression model.ResultA total of 2 207 electronic cases were collected，including 174 cases in the exposure group （Biejiajianwan group） and 2 033 cases in the non-exposure group. After propensity score matching， there were 174 cases in the exposure group and 174 cases in the non-exposure group. The Kaplan-Meier method was used for survival analysis on the matched data， and the Log-rank test results showed that the survival rate of patients with primary liver cancer in the Biejiajianwan group was higher than that in the control group （χ2=12.193， P<0.01）. Cox proportional hazards regression model analysis showed that the regression coefficient of Biejiajianwan was -0.916 4 with the hazard ratio （HR） ［95% confidence interval （CI）］=0.4 （0.239 5-0.668 0）， P<0.01， and the regression coefficient of radiofrequency ablation treatment was -0.976 5 with HR （95% CI）=0.376 6 （0.172 8-0.821 1， P<0.05）. Fibrinogen （FIB） abnormal regression coefficient was 0.481 4 with HR （95% CI）=1.618 4（1.022 0-2.562 9），P<0.05.ConclusionBiejiajianwan can prolong the survival period of patients with primary liver cancer. Radiofrequency ablation is an independent protective factor for Biejiajianwan in the treatment of primary liver cancer，while abnormal FIB are independent risk factors for Biejiajianwan in the treatment of primary liver cancer.关键词：primary liver cancer;Biejiajianwan;real-world study;retrospective cohort study;propensity score models
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发布时间：2023-02-07 - 摘要：ObjectiveTo explore the comprehensive clinical value of Qianlieping capsules in the treatment of chronic prostatitis with damp-heat stasis syndrome， and to provide evidence for the decision-making of clinical basic drug management.MethodBased on the "Guidelines for Comprehensive Clinical Evaluation of Drugs （Trial Version 2021）"， this study systematically reviewed the existing research on the treatment of chronic prostatitis with damp-heat stasis syndrome by Qianlieping capsules. Based on evidence-based medicine， clinical epidemiology， clinical medicine， evidence-based pharmacy， pharmacoeconomics， health statistics， health technology assessment， and other disciplines， the multi-criteria decision analysis model （MCDA） and CSC 2.0 software were used. The six dimensions of safety， effectiveness， economy， innovation， suitability， and accessibility of drugs， as well as traditional Chinese medicine（TCM） characteristics， were comprehensively evaluated qualitatively and quantitatively.ResultIn terms of safety， based on the spontaneous reporting system （SRS） of the National Center for ADR Monitoring， safety literature analysis， pharmacological and toxicological experiment report， and other evidence， the safety grade of Qianlieping capsules was evaluated as grade A， with good safety. In terms of effectiveness， based on the results of pharmacological and pharmacodynamic studies and Meta-analysis， and combined with the value and quality of the evidence for efficacy， the final efficacy grade of Qianlieping capsules was rated as B. In terms of economy， Qianlieping capsules was a class B drug of national medical insurance. Compared with those of similar Chinese patent medicines， the average daily cost of Qianlieping capsules was moderate， and there was no related cost increase during the administration process. Economic research showed that Qianlieping capsules combined with α-receptor blockers were more economical than α-receptor blockers alone. Based on the quality evaluation of economic evidence and the value evaluation of economic evidence， the economic grade of Qianlieping capsules was rated as B. In terms of innovation， Qianlieping capsules were a combination of cold and warm drugs， focusing on clearing heat， detoxifying， removing blood stasis， and relieving pain， with non-toxic medicinal materials. They obtained a number of invention patents. The enterprise service system was perfect， and the quality standard was higher than the international and Chinese standards. The innovation grade of Qianlieping capsules was rated as B. In terms of suitability， the results of the questionnaire survey showed that it had relatively good suitability for clinicians， nurses， pharmacists， and patients who used Qianlieping capsules. The information on Chinese patent medicines was complete and met the requirements of national standards. The suitability grade of Qianlieping capsules was rated as A. In terms of accessibility， Qianlieping capsules were moderately priced and affordable， with sufficient resources of medicinal materials， no shortage of medicinal materials， and good availability. The accessibility grade of Qianlieping capsules was rated as B. In terms of TCM medicine characteristics， the prescription of Qianlieping capsules was derived from Danshen Huoxue Decoction. The original prescription was used for the treatment of chronic prostatitis with blood stasis syndrome. The whole formula was recorded in The Complete Compendium of Fine Formulas （《良方大全》） published by Beijing Publishing Group Co.， Ltd. in 1991 and has been used for more than 30 years. The formula was a combination of warm and cold drugs， attacking pathogens without hurting healthy Qi. The grade of TCM characteristics of Qianlieping capsules was rated as B.ConclusionBased on the above "6+1" dimensions， the comprehensive evaluation result of Qianlieping capsules in the treatment of chronic prostatitis with damp-heat and blood stasis syndrome is grade B， and it is recommended to convert it into the relevant policy results of basic clinical drug management according to the conditions.关键词：Qianlieping capsules;chronic prostatitis;comprehensive clinical evaluation;effectiveness;safety;economy
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发布时间：2023-02-07 - 摘要：ObjectiveTo identify the functions of the AP2/ERF family members in Pinellia ternata and promote the genetic improvement of P. ternata varieties.MethodWe identified and conducted a systematic bioinformatics analysis of the AP2/ERF family member genes in P. ternata based on the three generations of transcriptome data. Real-time polymerase Chain reaction （Real-time） PCR was employed to determine the expression pattern of AP2/ERF genes in different tissues and under different stress conditions.ResultA total of eight full-length AP2/ERF family members were identified from the transcriptome data， which were classified into three sub-gene families： AP2， ERF， and DREB. The deduced AP2/ERF proteins in P. ternata had the length of 251-512 aa， the theoretical pI of 5.29-11.72， the instability index of 45.90-82.41， subcellular localization in the nucleus， and conserved domains and motifs. AP2/ERF genes were expressed in different tissues of P. ternata， with high expression levels in the leaf. The stress response experiments showed that PtERF1 mainly responded to NaCl stress. The expression of PtERF2 and PtERF4 was significantly up-regulated under low temperature and polyethylene glycol （PEG）-simulated stress. PtERF3 responded to both low temperature and NaCl stress. The expression of PtERF5 was induced by high temperature， low temperature， NaCl and PEG stress. The expression of PtERF7 was up-regulated under high temperature， while that of PtERF8 under low temperature.ConclusionThe AP2/ERF genes in P. ternata can respond to stress and have the potential functions of regulating photosynthesis and improving root stress resistance.关键词：Pinellia ternata;AP2/ERF gene family;gene identification;expression analysis
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发布时间：2023-02-07 - 摘要：ObjectiveTo discuss the thought of treatment of orifices in the Chinese herbal classics in the past dynasties based on the correspondence between drugs and symptoms to guide the clinical treatment based on syndrome differentiation.MethodAll the literature data of Chinese herbal classics were retrieved from the database of the Chinese Medical Dictionary， involving 76 works of Chinese herbal classics and covering representative works from the Han dynasty to the Ming and Qing dynasties. The information on Chines herbal drugs for the treatment of orifices was collected and sorted out. According to Chinese Materia Medica （11th Edition） and Pharmacopoeia of the People's Republic of China （2020 Edition）， the nature， flavor， and meridian tropism of the selected Chinese herbal drugs were statistically analyzed. The pathogenesis elements in the treatment of orifices were classified and counted， and the contents of syndrome differentiation and treatment in various Chinese herbal classics were extracted.ResultIn 76 Chinese herbal classics in the past dynasties， 93 Chinese herbal drugs for the treatment of orifices were selected. The nature of drugs was mainly warm， followed by cold and mild. The flavor was mainly pungent， followed by bitter and sweet. In terms of meridian tropism， drugs mainly acted on the lung meridian， followed by stomach， heart， liver， spleen， and kidney meridians. The pathogenesis elements of orifices could be divided into six categories， i.e.， wind invasion， turbid obstruction and Qi stagnation， water and dampness stagnation， blood stasis and collaterals blockage， heat and toxin damage， deficiency of vital Qi and cold coagulation.ConclusionOrifices are mainly treated with drugs effective in dispelling wind and pathogenic factors， resolving turbidity and removing stagnation， inducing diuresis and eliminating dampness， promoting blood circulation and dredging collaterals， clearing heat and purging fire， tonifying deficiency and dispelling cold， which are used in combination. Eliminating pathogenic factors and dredging， tonifying deficiency and purging excess are the main characteristics of treatment of orifices based on syndrome differentiation， which is in line with the physiological dysfunction state of orifices in losing the function， evil Qi blockage and healthy Qi deficiency.关键词：orifices;Chinese herbal drugs;literature;disturbance of orifices;traditional Chinese medicine therapy;clinical application
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发布时间：2023-02-07 - 摘要：Cerebral ischemia-reperfusion is a serious cerebrovascular disease with high morbidity and mortality. In recent years， reperfusion therapy based on thrombolysis and thrombectomy has been the main treatment method for patients with ischemic stroke. Numerous studies have shown that Chinese medicine saponins can effectively interfere with cerebral ischemia-reperfusion in a multi-target and multi-way manner， which have great potential on the treatment and prevention of cerebral ischemia-reperfusion. Taking China National Knowledge Infrastructure （CNKI） literature database and Wanfang literature database as the analysis sources， this paper used SPSS statistics to summarize the number of papers on the treatment of cerebral ischemia-reperfusion with Chinese medicine saponins and CiteSpace to conduct cluster analysis on the high-frequency keywords of the research， thereby expounding the research hotspots and research status of Chinese medicine saponins in the treatment of cerebral ischemia-reperfusion. Based on literature analysis and summary of animal experiments on the treatment of cerebral ischemia-reperfusion with Chinese medicine saponins in the past two decades， Chinese medicine saponins exerted effects by anti-inflammation， inhibition of oxidative stress， immune regulation， protection of nerve cells， inhibition of thrombosis， promotion of thrombolysis， protection of mitochondria， blood-brain barrier repairing， and other ways. The specific mechanism， therapeutic effect， and signaling pathway of each Chinese medicine saponin have been summarized in this study， which provide a theoretical basis for the in-depth research， new drug development， and clinical application of Chinese medicine saponins for the treatment of cerebral ischemia- reperfusion.关键词：cerebral ischemia-reperfusion injury;Chinese medicine saponins;mechanism;signaling pathway
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发布时间：2023-02-07 - 摘要：ObjectiveTo study the medication rules of Professor. WANG Xingkuan and inherit his academic experience in the treatment of chest stuffiness and pain with the aid of the Traditional Chinese Medicine Inheritance Computing Platform V3.0 （TCMICS V3.0）.MethodThe original medical records of patients with angina pectoris in coronary heart disease （CHD） diagnosed and treated by Prof. WANG in the outpatient department of Hunan University of Chinese Medicine from 2017 to 2020 were collected and entered into the TCMICS V3.0. The rules of prescriptions and drugs were analyzed by the software.ResultA total of 1 044 prescriptions of Prof. WANG for the treatment of chest stuffiness and pain were collected. Most of the drugs were sweet and bitter in flavor and mainly acted on the lung meridian， followed by heart， spleen， liver， stomach， and kidney meridians. Among the prescriptions， Shengmaisan was the most commonly used classic prescription， and Xintongling No. Ⅲ was the top experienced prescription. High-frequency drugs mainly included Ophiopogonis Radix， Pinelliae Rhizoma， Salviae Miltiorrhizae Radix et Rhizoma， Trichosanthis Pericarpium， Coptidis Rhizoma， Schisandrae Chinensis Fructus， and Bupleuri Radix. The common doses of drugs were 3， 5， 10， and 15 g. The analysis of formulation rules revealed 129 combinations of common drugs， 58 combinations with confidence > 0.99， and the core drugs of common syndromes. Six core drug combinations were obtained by drug clustering.ConclusionProfessor WANG treats chest stuffiness and pain based on syndrome differentiation following the principles of benefiting Qi， nourishing Yin， eliminating phlegm， resolving stasis， soothing liver， and promoting bile secretion， reflecting his academic idea of "regulation of multiple organs and comprehensive treatment". The core prescriptions can be used for reference by clinical practitioners， but further clinical and experimental studies are still needed to verify their efficacy.关键词：data mining;angina pectoris in coronary heart disease;classical formulas;chest stuffiness and pain;experience inheritance;medication rules
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发布时间：2023-02-07 - 摘要：This paper discusses the theoretical basis of traditional Chinese medicine （TCM） for the treatment of cancer-related fatigue （CRF） based on the principle of treating overstrain with warming in the Huangdi's Internal Classic 《黄帝内经》 and the role of hypothalamic-pituitary-adrenal （HPA） axis dysregulation in CRF， aiming to provide new ideas for the clinical treatment of CRF. In the pulsatile regulation of the HPA axis， cortisol， which is synthesized and released by the adrenal cortex， plays an essential role in the life activities. The abnormal circadian rhythm and reduced serum level of cortisol are major factors leading to CRF. Therefore， increasing the serum level and stimulating the biological activity of cortisol and restoring the normal function of HPA axis are important targets for the treatment of CRF and also the key to the TCM treatment of this disease. According to the TCM principle of treating overstrain with warming， we interpreted the etiology and clinical manifestations of overstrain and further explored the causes of CRF. It is believed that the depletion of Qi and blood， Yin and Yang， and fluid in the kidney， spleen， and liver is the key of the disease， which results in symptoms such as fatigue. Further， we elaborated on the theoretical connotation of warming and summarized the two main treatment principles of tonifying with warm-natured herbs and relieving fever with sweet- and warm-natured herbs. According to the different characteristics of the organs affected by pathogen， we proposed the treatment method of warming kidney to cultivate essence， warming stomach and nourishing spleen to replenish Qi， nourishing liver and tonifying blood to promote Qi movement， and relieving fever with sweet- and warm-natured herbs to alleviate fatigue. The warming method can elevate the serum level and invigorate the biological functions of cortisol in CRF patients， which provides a new theoretical basis for alleviating the symptoms and improving the quality of life of cancer patients in clinical practice.关键词：treating overstrain with warming;cancer;fatigue;hypothalamic-pituitary-adrenal （HPA） axis;cortisol
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发布时间：2023-02-07 - 摘要：In recent years，with the change in lifestyle and social environment and the increase in pressure in both life and work，male fertility has decreased significantly in China，and the incidence of male infertility has increased year by year，which has brought great challenges to andrologists. Traditional Chinese medicine （TCM） has a definite curative effect in the treatment of male infertility and is widely applied in clinical practice. In order to clarify the role of TCM in different types and each stage of male infertility，the China Association of Chinese Medicine （CACM） invited outstanding young andrologists in the clinic of TCM and western medicine to discuss topics such as idiopathic oligospermia and teratospermia，abnormal semen liquefaction，varicocele，immune infertility，improving success ratio of assisted reproductive technology，and ameliorating depression or anxiety. They conducted in-depth discussions on the advantages，characteristics，disadvantages，diseases responding specifically，and advantageous aspects of TCM treatment. The causes of male infertility and related links of treatment were summarized. Due to the unclear etiology and complex pathogenesis of male infertility，western medicine cannot achieve a good curative effect，while TCM，taking the holistic view as the core，specializes in improving functional diseases and can correspond to multiple targets and factors，with comprehensive treatments such as internal treatment and external treatment. This study summarized the advantageous diseases and advantageous stages of TCM treatment alone and integrated TCM and western medicine treatment and put forward suggestions for the treatment of the diseases by TCM and western medicine in order to promote the therapeutic effects and advantages of TCM among andrologists，increase mutual learning and communication between TCM and western physicians，provide patients with excellent and personalized treatment plans in clinical practice，and improve the curative effect of male infertility and fertility of males in China.关键词：male infertility;diseases responding specifically to traditional Chinese medicine（TCM）;expert consensus
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发布时间：2023-02-07 - 摘要：Experimental research on male infertility is critical to the study of the pathogenesis of male infertility and the evaluation of drug therapy. This paper reviewed animal experiments on male infertility in recent years. The experimental models of male infertility mainly include oligoasthenozoospermia （OA），teratozoospermia，azoospermia， and varicocele animal models. The OA animal models are mostly induced by glycosides of Tripterygium wilfordii （GTW）， adenine，hydrocortisone， and radiation，which are mainly chemical means. The animal models of azoospermia were usually constructed by intraperitoneal injection of bissulfonyl alkylating agent busulfan and immersion of scrotum in 43 ℃ water. There are few studies on animal models of teratozoospermia，and the induction methods by GTW and methyl methanesulfonate（MMS） are common. The animal models of varicocele-caused infertility are usually induced by operation. The ligation of the middle division of the left renal vein between the lateral inferior vena cava and the medial spermatic vein has a significant influence on testicular morphology and epididymal sperm quality. Animal experimental studies have shown that classic prescriptions for tonifying the kidney and promoting spermatogenesis represented by Wuzi Yanzongwan and clinical empirical prescriptions by modern research have played a significant role in the treatment of male infertility. The mechanism of tonifying the kidney in the treatment of male infertility mainly focuses on inhibiting spermatogenic cell apoptosis. The kidney-tonifying method can regulate the apoptosis of spermatogenic cells，which provides a new treatment idea and a reliable scientific basis for traditional Chinese medicine in the field of male reproduction.关键词：male infertility;animal experiment;kidney-tonifying and spermatogenic method;Wuzi Yanzongwan
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发布时间：2023-02-07 - 摘要：Respiratory diseases are common， frequently-occurring clinical diseases. As the prevalence rate is increasing year by year， they have become a problem that seriously affects public health. The diseases are mainly located in the lung by traditional Chinese medicine （TCM） syndrome differentiation. Lung governs Qi and controls breathing and is also an organ for the storage of phlegm. Clinically， phlegm and Qi are often used for the treatment. Banxia Houputang （BHT）， originated from Synopsis of the Golden Chamber （《金匮要略》）， was used to treat plum-stone Ai （globus hystericus） at first. It is composed of Rhizoma Pinelliae， Cortex Magnoliae Offcinalis， Poria， Rhizoma Zingiberis Recens， and Folium Perillae， and treats diseases with the core pathogensis of mutual obstruction of phlegm and Qi. BHT has the effects of moving Qi， dissipating mass， descending adverse Qi， and resolving phlegm， which basically correspond to the pathological characteristics of the lungs. Clinical studies have confirmed that modified BHT can be used either alone or in combination with western medicine to treat chronic pharyngitis， asthma， chronic obstructive pulmonary disease， pneumonia， obstructive sleep apnea， upper airway cough syndrome and other respiratory diseases， with significant effects. It effectively improves the symptoms and signs of the diseases and reduces the recurrence rate. Basic research has shown that BHT plays anti-inflammatory， anti-oxidative stress， anti-apoptotic， autophagy-regulating， and iron overload-regulating roles by regulating the targets in multiple pathways. This paper， by combing the relevant literature in recent years， conducted a systematic review on BHT from the three aspects of syndrome analysis， clinical treatment research and mechanism research， with a view to providing theoretical basis and reference for the mechanism research of BHT in treating respiratory diseases and for expanding its clinical application.关键词：Banxia Houputang;treating different diseases with the same treatment;respiratory disease;treatment based on syndrome differentiation;pharmacological effects;clinical application;review
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发布时间：2023-02-07 - 摘要：Central nervous system （CNS） is a sophisticated system subject to complex regulation， which dominates the high-level neural activities of the human body. Due to its complex physiological structure and refined regulatory mechanism covering a variety of diseases， CNS is the place where many chronic， refractory and rare diseases occur. Nerve cell is the basic unit of CNS， and its dysfunction and death is the root cause of CNS diseases. Ferroptosis is a new form of programmed cell death proposed in recent years， and has been proved to be closely related to the production and development of multiple CNS diseases. Traditional Chinese medicine （TCM）， including Chinese herbs， acupuncture and moxibustion， and massage， has shown unique advantages in the treatment of CNS diseases for a long time. A large number of studies have demonstrated that TCM participates in the regulation of CNS diseases via regulating ferroptosis and shows a good research prospect. This paper summarized the characteristics of ferroptosis and discussed the association between ferroptosis and CNS diseases in pathological mechanism. We also reviewed the regulation of various CNS diseases by different TCM interventions through ferroptosis， providing references for TCM to participate in the treatment of CNS diseases properly in the future.关键词：ferroptosis;traditional Chinese medicine;central nervous system;acupuncture and moxibustion
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发布时间：2023-02-07 - 摘要：ObjectiveMalignant tumor has become a serious public health problem， threatening human health. Chinese herbal medicine has become a research focus as it is "simple， convenient， inexpensive， and effective" and exerts anti-tumor effect through "multiple components， multiple targets， and multiple pathways". This paper reviews the anti-tumor effect of triterpenes， polysaccharides and other compounds in Poria， which is expected to serve as a reference for research on the anti-tumor effect of Poria.MethodBasic research， clinical observation， and reviews were retrieved from PubMed， Google Scholar， and China National Knowledge Infrastructure （CNKI） （1995—2022） with the keywords of Poria and malignant tumor.ResultThe main active components of Poria such as triterpenes represented by pachymic acid and polysaccharides represented by pachyman had extensive pharmacological effects in inhibiting the proliferation of malignant tumors， inducing apoptosis， suppressing invasion and metastasis， regulating the immune function， and improving the quality of life. In addition， the cultivation method， medicinal part， growth environment， and harvest cycle of the medicinal plant， and dosage form and processing method of Poria affected the content of different active components.ConclusionThe active components of pachymic acid and triterpenoids have great potential in antitumor， which， however， face the challenges in innovation and quality clinical trials. The lack of quality control standard of Poria may affect the anti-tumor effect， and efforts should be made to formulate specific standard for quality control. The antitumor of Poria is science-based and thus it has broad application prospect. Nevertheless， more efforts should be made before the practical application.关键词：Poria;triterpenes;polysaccharides;antitumor;theory convergence;influencing factor
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发布时间：2023-02-07 - 摘要：Digestive tract diseases， especially digestive tract tumors， including liver cancer， pancreatic cancer， and colorectal cancer， have high incidence in China. Digestive tract tumor is one of the top 10 cancers in terms of the number of new cases and deaths in the world， and the incidence and mortality of tumor diseases have been increasing year by year. Therefore， the prevention and treatment of tumors is particularly important. With the application and promotion of traditional Chinese medicine in the medical field and the rapid development of molecular biology and pharmacology， more and more potential active components of Chinese medicinal materials have been extracted and studied. These active components can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an effective component extracted from the skin of Bufo bufo gargarizans. It has been prepared into a variety of agents with anti-tumor， immunomodulatory， cardiac boosting， pain-easing， anti-inflammatory， and swelling-relieving activities. In clinical practice， cinobufotalin is mainly used to assist the treatment of liver cancer， lung cancer， colorectal cancer， gastric cancer and other malignant tumors， which can reduce the adverse reactions of patients in the middle and late stages and improve the quality of life and five-year survival rate of patients. The available studies of molecular mechanism have demonstrated that cinobufotalin can play a therapeutic role by inducing cell apoptosis， regulating cell cycle， inhibiting cell proliferation and angiogenesis， modulating immune response， reversing multidrug resistance， enhancing radiochemotherapy sensitivity， inhibiting tumor inflammation， invasion， and metastasis， etc. This review focuses on the clinical application and mechanism of cinobufotalin against digestive tract tumors in recent years， aiming to provide a theoretical basis for the anti-tumor research of cinobufotalin， promote the application of cinobufotalin in tumor treatment， and facilitate the further research and development of this compound.关键词：digestive tract tumor;cinobufotalin;anti-tumor effect;clinical application;review
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发布时间：2023-02-07 - 摘要：Intervertebral disc degeneration is one of the common causes of chronic low back pain. As a common spinal disease， its clinical symptoms are mainly low back pain and limited function， which seriously affects physical and psychological health. Because of its complex and unclear pathogenesis， the treatment of intervertebral disc degeneration has been the focus of scientific researchers and clinical workers. At present， the treatment of intervertebral disc degeneration mainly includes non-surgical therapy and surgical therapy， which can alleviate the clinical symptoms of patients to a certain extent， but easily induce new complications， and it is difficult to restore the normal physiological function of the intervertebral disc. In recent years， along with the advanced research on matrix metalloproteinases （MMPs） in the tissues of intervertebral disc degeneration， it has been found that MMPs can be used as molecular therapeutic targets. The expression of MMPs in the intervertebral disc tissues can be regulated by reducing the content and composition of the extracellular matrix of the intervertebral disc， so as to slow down intervertebral disc degeneration and even reverse the occurrence of intervertebral disc degeneration. This treatment is expected to delay intervertebral disc degeneration caused by changes in extracellular matrix composition or content. In recent years， with the continuous development of network pharmacology and bioinformatics research， a large number of researchers have explored the treatment of intervertebral disc degeneration by traditional Chinese medicine （TCM） and found that TCM can reduce the degradation of extracellular matrix by inhibiting the expression of MMPs， thus alleviating the symptoms of intervertebral disc degeneration and slowing down the progression of intervertebral disc degeneration. This paper reviewed the research progress of TCM intervention in MMP expression in the treatment of intervertebral disc degeneration， aiming at providing references for the application of TCM in the prevention and treatment of intervertebral disc degeneration.关键词：traditional Chinese medicine;matrix metalloproteinase;intervertebral disc degeneration;extracellular matrix
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发布时间：2023-02-07
- 摘要：By reviewing ancient materia medica， medical books， prescription books and modern literature， the herbal textual research of Sanguisorbae Radix has been conducted to verify the name， origin， evolution of scientific name， producing area， harvesting time， quality evaluation and processing methods. Through herbal textual research， the name of Diyu was first published in the Shennong Bencaojing， and has been used as the proper name of this herb for generations since then. The origin of the mainstream Diyu of previous generations was the roots of Sanguisorba officinalis or its variant S. officinalis var. longifolia. In ancient times， this herb was preferred to those with soft and fat roots， according to this characteristic， its origin should be S. officinalis var. longifolia. In modern literature， the root is preferred to those with thick， hard， pink or red sections， without rhizomes or fibrous roots， according to these characteristics， its origin should be S. officinalis. Most of the time， the past generation used Diyu directly. Occasionally， Sanguisorbae Radix was processed by frying with vinegar， baking or other methods. Since the Qing dynasty， the carbonized products has appeared and has continued to now. Based on research， it is recommended that the roots of S. officinalis var. longifolia should be used in the development of famous classical formulas， and the processing method should be selected according to the formula.关键词：famous classical formulas;Sanguisorbae Radix;herbal textual research;origin;producing area;quality evaluation;traditional Chinese medicine processing
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发布时间：2023-02-07 - 摘要：By reviewing ancient materia medica， prescription and medical books， combined with modern literature， the paper made textual research on the name， origin， producing area， quality evaluation， harvesting and processing methods of Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix， so as to provide a basis for the selection and use of these two herbs in the development of famous classical formulas. Through textual research， it can be found that Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix were mixed together in the early history of China， but the distinction was first made during the Southern and Northern dynasties， and since then there have been constant controversies， and it is not until contemporary times that they are distinguished clearly. In the past dynasties， Duhuo and Qianghuo were used as the rectification of names， some aliases and trade names were also seen. Angelica biserrata is the mainstream origin of Angelicae Pubescentis Radix in the past dynasties， and there are many plants belonging to Angelica， Heracleum and Aralia， which are also used as this medicine. However， the origin of Notopterygii Rhizoma et Radix used in the past dynasties is mostly Notopterygium incisum or N. franchetii， which is relatively uniform. The producing areas of Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix are mostly concentrated in the western and northwestern regions of China， among which Angelicae Pubescentis Radix is mainly produced in Hubei， Chongqing， Sichuan， Shaanxi and other places， and the border area between Hubei and Chongqing is the geo-authentic area. Notopterygii Rhizoma et Radix is mainly produced in Sichuan， Gansu， Qinghai， Shaanxi and others with the western and northern Sichuan and southern Gansu as the geo-authentic areas. Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix in the past dynasties were harvested in spring and autumn， especially in February and August of the lunar calendar. Angelicae Pubescentis Radix with strong main roots， few branches， firm texture and strong aroma is superior， and Notopterygii Rhizoma et Radix with strong rhizomes， tightly raised knots， purple-brown skin， tight cross-section， strong aroma and silkworm-like shape is superior. The processing methods of Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix are mostly cut after cutting the reeds， and the raw product is used as medicine. Based on the above research results， it is recommended that the roots of A. biserrata should be used for Angelicae Pubescentis Radix and the roots of N. incisum should be used for Notopterygii Rhizoma et Radix in the development of famous classical formulas， and raw products should be used in the formulas that do not specify processing requirements.关键词：famous classical formulas;herbal textual research;Angelicae Pubescentis Radix;Notopterygii Rhizoma et Radix;origin;harvesting and processing;traditional Chinese medicine processing
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发布时间：2023-02-07 - 摘要：By reviewing ancient materia medica， prescription books， medical books and modern literature， this article makes a systematic textual research on the name， origin， commercial specification， producing area， harvesting and processing of Scutellariae Radix used in famous classical formulas according to the historical development， in order to provide a reference for the development and utilization of famous classical formulas. Scutellariae Radix was first named as Qian， Qin and so on， while Huangqin was used as the official name in ancient literature， as well as many aliases such as Fuchang， Huangwen and Dufu. The main origin of Scutellariae Radix in the past dynasties was Scutellaria baicalensis， and other Scutellaria plants were also used for Scutellariae Radix at different times. The medicinal parts of Scutellariae Radix in all dynasties are roots， since the Northern and Southern dynasties， it has gradually differentiated into Ziqin and Kuqin with different efficacy according to their different growth stages and characteristics， and continued to this day. At present， most of Scutellariae Radix are Ziqin in the market， due to the influence of cultivation cost， index component content requirements and other factors. The production area of Scutellariae Radix recorded in ancient literature was wide and gradually expanded from the Yangtze River basin to the northward. Since modern times， Chengde city of Hebei province has been respected as a geo-authentic area， now S. baicalensis is cultivated in a wide area， spreading over north and northeast China. Scutellariae Radix was mostly used as raw products in the early period， and a variety of processed products appeared in the Ming dynasty. Development continues to this day， Scutellariae Radix mainly includes raw products and wine-processed products. According to the research conclusion， it is suggested that S. baicalensis should be used as Scutellariae Radix in famous classical formulas， and the selection of its commercial specifications and processed products can be comprehensively determined according to the requirements of original prescription and the clinical effect.关键词：famous classical formulas;Scutellariae Radix;origin;producing area;commercial specification;processing method;herbal textual research
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发布时间：2023-02-07 - 摘要：By reviewing ancient materia medica， medical books and modern literature， this paper conducted a systematic research on name， origin， scientific name evolution， producing area， quality， harvesting and processing methods of Alpiniae Officinarum Rhizoma. The results showed that Alpiniae Officinarum Rhizoma was first published in Mingyi Bielu， and its correct name was Gaoliangjiang. The mainstream origin of Alpiniae Officinarum Rhizoma used in the past dynasties is Alpinia officinarum， which is used to this day， while it used to be mixed with A. galanga because of the similar name and morphology. Alpiniae Officinarum Rhizoma produced in Danzhou and Leizhou was considered to be better in ancient times， and now it mainly produced in Guangdong， Guangxi and Hainan provinces. In addition， it has been concluded that Alpiniae Officinarum Rhizoma with reddish brown， sturdy and firm character， wrinkled skin， convex flesh， aromatic and spicy taste， and few branches is the best. In ancient times， Alpiniae Officinarum Rhizoma was commonly harvested in February and March， whereas it generally harvested in late summer or early autumn at present， and wild products are usually harvested before the rainy season in May. The main processing methods of Alpiniae Officinarum Rhizoma are cleansing and cutting， and some other methods are stir-frying or mixing with auxiliary materials. Based on the research results， it is suggested that the raw products of A. officinarum rhizomes or its processed products according to prescription requirements should be used in the development of famous classical formulas containing Alpiniae Officinarum Rhizoma.关键词：Alpiniae Officinarum Rhizoma;herbal textual research;famous classical formulas;evolution of scientific name;producing area;quality evaluation;traditional Chinese medicine processing
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发布时间：2023-02-07
Medicine research Tipic of famous classical formulas (Ⅰ)
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