Abstract：ObjectiveTo explore the neuroprotective effect of Buyang Huanwutang （BYHW） on diabetic peripheral neuropathy （DPN） rats by regulating SIRT1/p53 pathway and to clarify the mechanism and the dosage of astragalus in the prescription.MethodA total of 90 SD rats were randomized into control group， DPN group， DPN + BYHW containing 120 g Astragalus （at 15 g·kg-1·d-1） （BYHW120 group）， DPN + BYHW containing 60 g Astragalus （at 8.75 g·kg-1·d-1） （BYHW60 group）， DPN + BYHW containing 30 g Astragalus （at 5.625 g·kg-1·d-1） （BYHW30 group）， and DPN + α-lipoic acid （at 60 mg·kg-1·d-1） （ALA group）. Standard diet was given to rats in the control group and high-carbohydrate/high-fat diet and streptozotocin （ip） were used to induce diabetes in rats in other groups. The administration lasted 12 weeks. After the intervention， mechanical pain threshold and nerve conduction velocity were detected. The L4-5 dorsal root ganglions were stained with haematoxylin-eosin （HE） and toluidine blue to observe the pathological changes， and the apoptosis of nerve cells was detected by terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling （TUNEL） assay. Cleaved cysteinyl aspartate-specific proteinase-3 （Caspase-3）， and the main proteins in the SIRT1/p53 pathway， such as silencing information regulator 2 related enzyme 1 （SIRT1）， acetyl-p53， dynamin-related protein 1 （Drp1）， Bcl-2 associated X protein （Bax）， and B-cell lymphoma-2 （Bcl-2）， were detected by immunohistochemistry and Western blot.ResultCompared with the control group， the DPN group presented increase in blood glucose （P<0.01）， decrease in nerve conduction velocity and mechanical pain threshold （P<0.01）， rise of the percentage of positive cells （TUNEL assay， the same below） and the expression of cleaved Caspase-3 （P<0.01）， drop in the expression of SIRT1 （P<0.01）， and elevation of acetyl-p53， Drp1， and Bax/Bcl-2 ratio （P<0.01）. Cleaved Caspase-3， acetyl-p53， Drp1， and Bax/Bcl-2 ratio in each administration group decreased as compared with those in the DPN group （P<0.01）. Nerve conduction velocity， mechanical pain threshold （P<0.05， P<0.01）， and the percentage of positive cells （P<0.05， P<0.01） increased in the administration groups as compared with those in the DPN group except for the BYHW30 group， and BYHW120 group and ALA group showed the increase in SIRT1 （P<0.05， P<0.01）. Nerve conduction velocity， mechanical pain threshold， and SIRT1 expression were lower （P<0.05， P<0.01） and expression of cleaved Caspase-3 was higher （P<0.01） in the BYHW60 and BYHW30 groups than in the BYHW120 group. The percentage of positive cells and the expression of acetyl-p53 were higher in the BYHW30 group than in the BYHW120 group （P<0.01）.ConclusionBYHW inhibits apoptosis and exerts therapeutic effect on DPN by regulating the SIRT1/p53 pathway. The therapeutic effect is related to the dosage of Astragalus in the prescription. BYHW containing 120 g Astragalus suppresses p53-dependent apoptosis more significantly than Buyang Huanwutang containing 60 g and 30 g of Astragalus.
Keywords：diabetic peripheral neuropathy;Buyang Huanwutang;astragalus;silencing information regulator 2 related enzyme 1 （SIRT1）/p53 pathway;apoptosis
Abstract：ObjectiveTo observe the protective effect of Sanhuatang and its modifications on the brain tissue of rats exposed to cerebral ischemia-reperfusion injury （CIRI） and explore its action mechanism and compatibility characteristics.MethodOne hundred and forty SD male rats of clean grade were randomly divided into the control group， sham-operation group， and operation group. The Longa suture method was employed to establish the CIRI model. The successfully modeled CIRI rats were further divided into five groups， namely the model group， nimodipine group， Sanhuatang without Notopterygii Rhizoma et Radix group， Notopterygii Rhizoma et Radix group， and Sanhuatang group， and treated with the corresponding medicines by gavage for five days. The cerebral infarct size in each group was examined by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and the pathological changes in the brain tissue were observed by hematoxylin-eosin （HE） staining and electron microscopy. The mRNA and protein expression levels of Claudin-5， Occludin， and zonula occludens-1 （ZO-1） in brain tissues were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively.ResultCompared with the control group， the model group exhibited markedly increased infarct size， obvious changes in brain morphology and ultrastructure， and down-regulated mRNA and protein expression of Claudin-5， Occludin， and ZO-1 （P<0.01）. Compared with the model group， both nimodipine and Sanhuatang significantly decreased the infarct size （P<0.01） and relived the pathological changes. The infarct sizes in the Sanhuatang without Notopterygii Rhizoma et Radix group and Notopterygii Rhizoma et Radix group were reduced without exhibiting a statistically significant difference. The mRNA and protein expression levels of Claudin-5， Occludin， and ZO-1 in the nimodipine group， Sanhuatang group， and Notopterygii Rhizoma et Radix group were up-regulated significantly in comparison with those in the model group （P<0.01， P<0.01）. The mRNA and protein expression levels of Claudin-5 and ZO-1 were higher in the Notopterygii Rhizoma et Radix group than in the Sanhuatang without Notopterygii Rhizoma et Radix group （P<0.01， P<0.01）.ConclusionSanhuatang exerts the protective effect against CIRI in rats possibly by regulating the expression of Claudin-5， Occludin， and ZO-1 and improving the blood-brain barrier function. Notopterygii Rhizoma et Radix in Sanhuatang may play an important role in the protection of rats from CIRI.
Keywords：Sanhuatang;Notopterygii Rhizoma et Radix;cerebral ischemia-reperfusion injury （CIRI）;blood-brain barrier;Claudin-5;Occludin;zonula occludens-1 （ZO-1）
Abstract：ObjectiveTo explore the effect of Danggui Niantongtang （DGNTT） on cell apoptosis and autophagy in rheumatoid arthritis （RA） fibroblast-like synoviocytes （FLS）.MethodRA-FLS were isolated and cultured from the synovial tissue of RA patients. The cells were treated with 10% blank serum （blank control group）， 10% sera containing low， medium and high doses of DGNTT. Wound healing assa and cell invasion test were applied to observe the effect of RA-FLS invasion technique. The apoptosis and autophagy level of RA-FLS cells was detected by Hoechst33342 method and monodansylcadaverine （MDC） staining. The mRNA and protein expression levels of B cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， microtubule-associated protein 1 light chain 3 （LC3）， autophagy key molecular yeast Atg6 homolog 1 （Beclin1） were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）and Western blot.ResultCompared with the blank control group，each dose of serum could slow down the wound healing and significantly Reduce the number of RA-FLS cells invading the lower chamber（P<0.01），the mRNA and protein expression levels of Bcl-2，LC3，Beclin1 were significantly decreased（P<0.01）， and Bax were significantly increased（P<0.01）. Hoechst33342 results showed that low， medium and high doses DGNTT could promote RA-FLS cell apoptosis. After MDC staining，autophagosome in low， medium and high doses DGNTT decreased significantly（P<0.01）.ConclusionDanggui Niantongtang can effectively inhibit the proliferation of fibroblast-like synoviocytes. Its mechanism may be related to promote apoptosis and inhibit autophagy of fibroblast-like synoviocytes.
Abstract：ObjectiveTo provide references for the selection of Zingiberis Rhizoma Recens on the research of famous classical formulas and the reasonable uses for medicines and foods through herbal textural research and quality analysis of Zingiberis Rhizoma Recens from main producing areas in China.MethodBy consulting the ancient and modern literature， the name， origin， producing areas， harvest time， processing methods of Zingiberis Rhizoma Recens were summarized. According to the 2020 edition of Chinese Pharmacopoeia， the contents of 6-gingerol， 8-gingerol， 10-gingerol， and volatile oil in Zingiberis Rhizoma Recens samples were determined.ResultHerbal textural research indicated that medicinal Zingiberis Rhizoma Recens originated from the fresh rhizome of Zingiber officinale. Before Tang dynasty， Zingiberis Rhizoma Recens produced in Sichuan was the best. In the Song dynasty， Zingiberis Rhizoma Recens produced in Sichuan， Zhejiang， and Anhui was of excellent quality. The cultivation of Zingiberis Rhizoma Recens in Shandong developed during the Ming and Qing dynasties. From ancient times to the present， the harvest period extended from the autumnal equinox to the winter solstice. Quality evaluation standards of Zingiberis Rhizoma Recens were essentially the same in ancient and present documents， as those with little gluten or gluten-free and strong pungency were preferred. After determination， the contents of 6-gingerol， 8-gingerol， and 10-gingerol in 44 samples were qualified in 27 samples， with a qualified rate of 61.4%. Among them， 17 samples were unqualified in the total contents of 8-gingerol and 10-gingerol. Among these qualified samples， the content of 6-gingerol ranged from 0.067% to 0.255%， and the total contents of 8-gingerol and 10-gingerol ranged from 0.040% to 0.131%. The content of volatile oil in 36 samples were qualified in 33 samples， with a qualified rate of 91.7%. Among the qualified samples， the content of volatile oil ranged from 0.175% to 0.410%.ConclusionZingiberis Rhizoma Recens has been used as medicines and foods since ancient times， and the genuine producing areas are consistent in ancient and present times， while the quality of the products， especially the medicinal Zingiberis Rhizoma Recens， should be monitored. Medicinal Zingiberis Rhizoma Recens planted in Leshan city of Sichuan province contains high contents of effective components， followed by Qujing and Wenshan cities of Yunnan province. Zingiberis Rhizoma Recens planted in Shandong and other places is mostly edible.
Abstract：ObjectiveTo observe the effect of Liuwei Dihuangtang on depression-like behavior of diabetes mellitus combined with comorbid depression （DD） rats， so as to explore its action mechanism.MethodFifty male SD rats of SPF grade were fed with high fat diet and injected with low-dose streptozotocin （STZ） via tail vein for inducing diabetes. Afterwards， the diabetic rats were exposed to chronic unpredictable mild stress （CUMS） for 28 d. The successfully modeled DD rats were randomly divided into five groups： model group， fluoxetine （10 mg·kg-1·d-1） group， and low-， medium-， and high-dose （3.375， 6.75， 13.5 g·kg-1·d-1） Liuwei Dihuangtang groups， with 10 in each group. Another 10 rats were classified into the normal control group and treated with intragastric administration of normal saline for four weeks. The tail suspension test and open field test were conducted to evaluate the depressive-like phenotype of rats. The contents of malondialdehyde （MDA）， reactive oxygen species （ROS）， 8-hydroxy-2 deoxyguanosine （8-OHdG）， superoxide dismutase （SOD）， and glutathione （GSH） in ventral hippocampus （vHIP） were measured by enzyme-linked immunosorbent assay （ELISA）， and the myelin basic protein （MBP） expression in vHIP by immunofluorescence assay. The expression levels of MBP， myelin protein lipoprotein （PLP）， myelin oligodendrocyte glycoprotein （MOG）， phosphorylated adenosine 5'-monophosphate-activated protein kinase （p-AMPK）/AMPK， phosphorylated protein kinase B （p-Akt）/Akt， phosphorylated glycogen synthase kinase 3β （p-GSK3β）/GSK3β， and nuclear factor erythroid-2 related factor 2（Nrf2） were determined by Western blotting.ResultCompared with the normal control group， the model group exhibited significantly prolonged immobility in the tail suspension test （P<0.01） and shortened residence at the central area in the open field test （P<0.01）. The immobility time in the medium- and high-dose Liuwei Dihuangtang groups declined to different degrees as compared with that of the model group （P<0.01）， while the residence time at the central area was significantly increased （P<0.05， P<0.01）. Compared with the normal control group， the model group displayed down-regulated MBP， PLP， and MOG protein expression in vHIP （P<0.01）. Compared with the model group， Liuwei Dihuangtang at the low dose up-regulated the expression of MBP （P<0.05）， but did not obviously affect the expression of MOG and PLP. Fluoxetine and Liuwei Dihuangtang at the medium and high doses up-regulated the expression of MBP， PLP， and MOG （P<0.05， P<0.01）. Comparison with the normal control group revealed that the MBP fluorescence intensity in vHIP of the model group was significantly weakened （P<0.01）. After the intervention， the MBP fluorescence intensities in the medium- and high-dose Liuwei Dihuangtang groups and fluoxetine group were enhanced in contrast to that of the model group （P<0.05， P<0.01）. SOD and GSH in the model group were lower than those in the normal control group （P<0.01）， whereas the MDA， ROS， and 8-OHdG expression levels were higher （P<0.01）. Compared with the model group， Liuwei Dihuangtang at the medium and high doses and fluoxetine all down-regulated the expression levels of MDA， ROS， and 8-OHdG （P<0.05，P<0.01）， while up-regulated SOD and GSH expression （P<0.05，P<0.01）. The expression levels of p-AMPK， p-Akt， and Nrf2 in the model group were down-regulated as compared with those in the control group， and the expression of p-GSK3β was up-regulated （P <0.01）. As demonstrated by comparison with the model group， the protein expression of p-AMPK in the low-dose Liuwei Dihuangtang group was elevated （P<0.05）， while p-Akt and Nrf2 were slightly increased， exhibiting no statistical significant difference. However， the protein expression levels of p-AMPK， p-Akt， and Nrf2 in the medium- and high-dose Liuwei Dihuangtang groups and fluoxetine group were up-regulated， while those of p-GSK3β were down-regulated （P<0.05，P<0.01）.ConclusionLiuwei Dihuangtang improves the depressive-like behavior of DD rats， which may be related to its activation of the AMPK/Akt/GSK3β/NRF2 pathway， regulation of the oxidative stress in vHIP， and enhancement of myelin repair.
Abstract：ObjectiveTo explore the intervention effect of Baofeikang granule （BFK） on the rat model of pulmonary fibrosis through the Wnt/β-catenin signaling pathway.MethodAfter adaptive feeding for one week， 50 healthy rats were randomly divided into a blank group （n=8） and an experimental group （n=42）. After anesthesia， the rats in the experimental group were injected with bleomycin sulfate solution （5 mg·kg-1） into the trachea for the induction of the pulmonary fibrosis model. Those in the blank group were injected with the same amount of normal saline under the same manipulation. On the 7th day after modeling， one of the remaining 33 rats alive was randomly removed， and the other 32 model rats were assigned into a model group （n=8）， a prednisone acetate （1.17 mg·kg-1） group （n=8）， a low-dose BFK （13.59 g·kg-1） group （n=8）， and a high-dose BFK （27.18 g·kg-1） group （n=8）. The rats in the groups with drug intervention were treated correspondingly by gavage once per day for 21 days， and those in the blank group and the model group received the same amount of normal saline. The pulmonary compliance and ventilatory function， the scores of pathological changes and fibrosis， the levels of type Ⅰ collagen （Col Ⅰ） in lung tissues and hydroxyproline （HYP） in the serum， and the relative expression of Wnt3a and β-catenin protein in lung tissues were compared.ResultCompared with the blank group， the model group showed reduced pulmonary function indexes， such as forced vital capacity （FVC）， peak expiratory flow （PEF）， the resistance of lung （RL）， and dynamic compliance （Cdyn） （P<0.05， P<0.01）， severely damaged lung tissue morphology， massive formed continuous fibrous foci， increased fibrosis score （P<0.01）， elevated levels of Col Ⅰ in lung tissues and HYP in the serum （P<0.01）， and up-regulated expression of Wnt3a and β-catenin （P<0.01）. FVC， PEF， and Cdyn levels in the prednisone acetate group and the BFK groups were higher than those in the model group （P<0.05， P<0.01）. Pathological changes were improved in the groups with drug intervention， and fibrosis scores were decreased as compared with the model group （P<0.05， P<0.01）. The scores in the BFK groups were lower than that in the prednisone acetate group （P<0.01）. The levels of Col Ⅰ and HYP in the groups with drug intervention were lower than those in the model group （P<0.05， P<0.01）. The level of Col Ⅰ in the prednisone acetate group was higher than that in the high-dose BFK group （P<0.01）. The levels of serum HYP in the BFK groups was lower than that in the prednisone acetate group （P<0.01）. The protein expression of Wnt3a in lung tissues of the high-dose BFK group was lower than that of the model group （P<0.05）. The protein expression of β-catenin in the prednisone acetate group and the BFK groups was lower than that in the model group （P<0.05， P<0.01）， and the expression level in the high-dose BFK group was lower than that in the prednisone acetate group （P<0.01）.ConclusionBFK can relieve bleomycin sulfate-induced pulmonary fibrosis， reduce collagen deposition， improve pulmonary compliance， and enhance pulmonary ventilatory function in rats. One of its mechanisms is presumedly the inhibition of the Wnt/β-catenin signaling pathway.
Keywords：Baofeikang granule;rats with pulmonary fibrosis;Wnt/β-catenin signaling pathway;collagen deposition
Abstract：ObjectiveTo observe the therapeutic effect and antioxidant mechanism of Xiaochuanning granule on psychological stress-related asthma in rats.MethodThe 6-week-old male SD rats were randomly divided into the normal group， asthma group， stress group， stress-related asthma group， western medicine group （atomization of budesonide suspension） and traditional Chinese medicine （TCM） group （Xiaochuanning granule 2.48 g·kg-1）. The asthma model was established during 28 days by intraperitoneal injection of 10% ovalbumin（OVA）on the 1st and 8th days and inhaling of vapourized 1% OVA started at the 15th day. Stress group， stress-related asthma group， western medicine group and TCM group were given restraint stimulation during the 28 days to establish the psychological stress-related asthma model. Rats in each group were administered with corresponding drug for 14 days from the 15th day. The sucrose preference test and open field test were performed at the 15th and 28th days. At the end of experiment， the body weight， serum interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） levels， as well as the levels of malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione （GSH） in lung tissues were detected by assay kits. Hematoxylin-eosin（HE） staining was conducted to observe the pathological changes in lung tissues. Meanwhile， Western blot was used to detect the protein expression of nuclear factor erythroid 2-related factor 2 （Nrf2） and hemeoxygenase-1 （HO-1） in lung tissues.ResultCompared with the stress-related asthma group， the body weight， sugar water consumption rate and open field distance in the TCM group were significantly increased （P<0.05）， and the serum IL-4， IL-5， IL-13 levels were significantly decreased （P<0.05）， the levels of SOD and GSH in lung tissues increased significantly （P<0.05）， while the level of MDA decreased significantly （P<0.05）. HE staining showed that the bronchial mucosal injury， inflammatory cell infiltration， gland hyperplasia， epithelial degeneration and necrosis were significantly ameliorated in the TCM group than in the stress-related asthma group. The expression of Nrf2 and HO-1 protein in lung tissues also increased significantly （P<0.05）.ConclusionXiaochuanning Granule can regulate the psychological stress state of stress-related asthmatic rats， alleviate airway inflammatory reaction， and suppress oxidation， which is related to its up-regulation of the Nrf2/HO-1 protein expression.
Abstract：ObjectiveTo explore the effect and mechanism of Sangmei Zhike granule （SMZK） on airway inflammation in rats with cough variant asthma（CVA）.MethodSix-week-old male SD rats were randomly divided into normal group， model group， and SMZK （2.48 g·kg-1） group. The rats in the model group and the SMZK group received intraperitoneal injection of a mixed solution containing 10% ovalbumin （OVA） and aluminium hydroxide on the 1st and 8th days and aerosol inhalation of 1% OVA solution from the 15th day for CVA model induction. The intervention lasted for two weeks from the 15th day. At the end of animal manipulation， the lung function was detected and inflammatory cells in the peripheral blood were counted. The serum interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-10 （IL-10） levels were determined. Hematoxylin-eosin （HE） staining was performed on the lungs. Western blot was used to detect the protein expression of nuclear factor kappa-B （NF-κB） and its inhibitor α（IκBα） in lung tissues.ResultCompared with the normal group， the model group showed reduced forced expiratory volume in the first 0.1 second （FEV0.1），FEV0.1/forced vital capacity （FVC），and forced expiratory flow 50% （FEF50%） （P<0.05， P<0.01）， increased white blood cells and eosinophils （P<0.01）， and up-regulated serum IL-4， IL-5， and IL-10 （P<0.01）. As revealed by HE staining， the model group displayed shed epithelial cells of the bronchus， airway stenosis， hyperplasia and expansion of mucous glands， disarrangement of layer structures， disorderly arranged cells， and extensive infiltration of inflammatory cells. The protein expression of NF-κB p65 was higher （P<0.01） and that of IκBα was lower （P<0.01） in the lung tissues of the model group than that in the normal group. Compared with the model group， the SMZK group showed increased FEV0.1，FEV0.1/FVC，and FEF50% （P<0.05）， decreased white blood cells and eosinophils in the peripheral blood （P<0.01）， and declining serum IL-4， IL-5， IL-10 （P<0.01）. HE staining demonstrated mild bronchial mucosal injury and relieved inflammatory cell infiltration， gland hyperplasia， and epithelial degeneration and necrosis in the SMZK group. The protein expression of NF-κB p65 was decreased （P<0.05） and that of IκBα was increased （P<0.05） in lung tissues of the SMZK group than that in the model group.ConclusionSMZK can improve lung function and inhibit airway inflammation in rats with CVA. The underlying mechanism may be related to the regulation of IκBα/NF-κB protein expression in the lungs.
Abstract：ObjectiveTo compare and evaluate the clinical efficacy of five classical prescriptions for acute attack of bronchial asthma （BA） and cough variant asthma （CVA） in children， and to further compare and assess the effect of them on cold-induced asthma or heat-induced asthma.MethodRandomized controlled trials （RCT） on the treatment of acute attack of asthma with five classical prescriptions （Sanzi Yangqintang， Maxing Shigantang， Shegan Mahuangtang， Xiao Qinglongtang， and Dingchuantang） were retrieved from China Science and Technology Journal Database （VIP）， China National Knowledge Infrastructure （CNKI）， and Wanfang Data （from establishment to August 15， 2021）. The eligible RCT were evaluated and the data were extracted for network Meta-analysis by Stata 16.0.ResultA total of eligible 47 RCT were screened out， involving 5 114 children with acute attack of asthma and 10 intervention measures. Among them， 16 RCT （1 912 children， 6 intervention measures） were about the cold-induced asthma and 10 RCT （1 054 cases， 4 intervention measures） focused on the heat-induced asthma. According to the Meta-analysis， among the 10 interventions， Maxing Shigantang + routine treatment of western medicine demonstrated the most significant effect， and the effect of the interventions was in the following order： Maxing Shigantang + routine treatment of western medicine > routine treatment of western medicine， Shegan Mahuangtang + routine treatment of western medicine> Xiao Qinglongtang + routine treatment of western medicine > Shegan Mahuangtang > Dingchuantang + routine treatment of western medicine. For the cold-induced asthma， the effect of Shegan Mahuangtang + routine treatment of western medicine was remarkable， and for the heat-induced asthma， the corresponding intervention was Dingchuantang + routine treatment of western medicine. Shegan Mahuangtang was outstanding in improving the percentage of forced expiratory volume in the first second in predicted value （FEV1%）.ConclusionThe combination of western medicine with the five prescriptions was more effective than the western medicine alone， particularly the combination with Maxing Shigantang. The combination of Shegan Mahuangtang and western medicine was outstanding in the treatment of cold-induced asthma， while the corresponding intervention for heat-induced asthma was the combination of Dingchuantang and western medicine. However， a large number of RCT with scientific design and higher quality are still needed to verify the conclusion.
Abstract：ObjectiveTo investigate the effects and mechanism of baicalin （BA） on lipopolysaccharide （LPS）-induced acute lung injury in rats.MethodEighty healthy male SD rats were randomly divided into the control group， model group， low-dose BA （BA-L） group， medium-dose BA （BA-M） group， high-dose BA （BA-H） group， dexamethasone （DEX） group， SB203580 group， and BA + SB203580 group， with 10 rats in each group. The rats in the BA-L， BA-M， and BA-H groups were injected intraperitoneally with different doses （10， 50， 100 mg·kg-1） of BA solution， the ones in the DEX group with 5 mg·kg-1 DEX solution， the ones in the SB203580 group with 0.5 mg·kg-1 SB203580 solution， the ones in the BA + SB203580 group with 100 mg·kg-1 BA solution and 0.5 mg·kg-1 SB203580， and those in both the control group and model group with the same volume of normal saline， once per day， for seven successive days. One hour after the last administration， rats in all groups except for the control group were given 5 mg·kg-1 LPS via intratracheal instillation for inducing the acute lung injury， whereas those in the control group received the same volume of normal saline solution. Twelve hours later， the lung tissues were sampled and stained with htoxylin-eosin （HE） for observing the pathological changes， followed by the counting of the total number of cells and neutrophils in bronchoalveolar lavage fluid （BALF）. The wet/dry weight ratio of the lung tissue and the contents of serum superoxide dismutase （SOD） and malondialdehyde （MDA） were measured. The activity of reactive oxygen species （ROS） in the lung tissue was detected by immunofluorescence and the levels of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in BALF by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was conducted to determine the relative expression of p-p38 mitogen-activated protein kinase （MAPK） and Western blotting was carried out to detect the protein expression levels of p-p38 MAPK， thioredoxin interacting protein （TXNIP）， NOD-like receptor protein 3 （NLRP3）， and cysteinyl aspartate specific protease-1 （Caspase-1） in the lung tissue.ResultCompared with the control group， the model group displayed inflammatory pathological changes in lung tissue， elevated wet/dry weight ratio， total number of cells and neutrophils in BALF， and ROS and MDA levels （P<0.01）， decreased SOD activity （P<0.01）， and up-regulated IL-1， IL-18， IL-6， TNF-α， p-p38 MAPK， NLRP3， and Caspase-1 expression （P<0.01）. Compared with the model group， BA at different doses， SB203580， and BA + SB203580 all effectively alleviated the pathological changes in lung tissue induced by LPS， reduce the lung wet/dry weight ratio， the total number of cells and neutrophils in BALF， and ROS and MDA levels （P<0.05，P<0.01）， enhanced the activity of SOD （P<0.05，P<0.01）， and down-regulated the expression of IL-1β， IL-18， IL-6，TNF-α， p-p38 MAPK， NLRP3， and Caspase-1 in lung tissue （P<0.05，P<0.01）.ConclusionBA has a protective effect against LPS-induced acute lung injury， which may be related to its inhibition of p38MAPK/NLRP3 signaling pathway and the improvement of inflammatory response.
Keywords：baicalin （BA）;lipopolysaccharide （LPS）;acute lung injury;p38 mitogen-activated protein kinase （MAPK）/ NOD-like receptor protein 3 （NLRP3） signaling pathway
Abstract：ObjectiveTo evaluate the in vivo and in vitro toxicity of Evodia Fructus water extraction and its index components， and provide a basis for basic research on the toxic substances of Evodia Fructus.MethodInstitute of Cancer Research（ICR） mice were divided into high， medium and low dose groups of water extraction of Evodia Fructus and a blank control group. The administration groups were respectively given 80，60，40 g·kg-1 water extraction of Evodia Fructus， the blank control group was given distilled water in equal volume， blood was taken 24 hours later to determine the serum alanine aminotransferase（ALT）and aspartate aminotransferase（AST）values， the liver was weighed and histopathological examination was performed. Evodia Fructus water extract， evodiamine， rutaecarpine and limonin were respectively acted on HepG2 cells for 24 h， and cell counting kit-8（CCK-8） method was used to investigate the cytotoxicity. The ICR Mice were divided into two groups， one group was given by oral gavage and the other group was given intraperitoneal injection. The two routes of administration were separately given 3 index components of Evodia Fructus， and the dosage was 200 mg·kg-1. Take blood 24 hours after administration to determine the activity of ALT and AST in serum， and take liver to calculate liver index.ResultCompared with the blank group， the high and medium dose groups of Evodia Fructus water extract were depressed 24 hours after administration， and the behavior of the low dose group was not significantly abnormal. The serum biochemical results showed that the activities of serum ALT and AST in the high and medium dose groups were significantly increased （P<0.01）， the activities of serum ALT and AST in the low dose group were significantly increased， and the histopathological results showed that the high and medium dose groups were significantly increased Punctate necrosis and vacuolar degeneration appeared in the liver of the medium dose group， and there was no obvious abnormality in the low dose group. Compared with the blank group， evodiamine and rutaecarpine had a certain inhibitory effect on the proliferation of HepG2 cells， but the inhibitory effect was not strong. Limonin had no significant inhibitory effect on the proliferation of HepG2 cells. Compared with the control group， the 3 index components of Evodia Fructus have no effect after oral administration. There was no significant difference in the activity of ALT and AST in serum of mice， and there was no significant difference in liver index. Intraperitoneal injection of evodiamine and rutaecarpine can cause the activity of serum ALT and AST to increase， and limonin can cause ALT activity was significantly increased （P<0.01）， and the liver index was significantly increased （P<0.05）.ConclusionEvodia Fructus water extract can cause acute liver injury in mice， Oral administration of evodiamine， rutaecarpine and limonin had no damage to the liver of mice. Intraperitoneal administration of evodiamine and rutaecarpine had no effect on liver injury in mice， and intraperitoneal administration of limonin could cause acute liver injury in mice.
Abstract：ObjectiveTo observe the effect of Wenyang Jieyu decoction （WYJY） on the hippocampal structure of depressed rats with kidney-yang deficiency.MethodThe 105 SD rats were randomly divided into normal group， model group， fluoxetine group （4.17 mg·kg-1）， Xiaoyaosan group （1.88 g·kg-1）， and low-， medium- and high-dose （1.25，2.50，5.00 g·kg-1） WYJY groups，15 in each group. The depression model was induced by subcutaneous injection of corticosterone in rats except for those in the normal group and the rats were orally administered once a day for 28 days. The depression-like behaviors of rats were observed by sucrose preference test， novelty-suppressed feeding test， forced swimming test， and open field test. The morphology of hippocampal neurons was observed by hematoxylin-eosin（HE） staining， and the density of hippocampal neurons was detected by Nissl staining. The ultrastructure of hippocampal synapses was observed by transmission electron microscopy （TEM）. The expression of synaptophysin （SYP）， postsynaptic density-95 （PSD95）， and apoptosis-related protein Caspase-3 in hippocampal neurons was observed by immunohistochemistry， and bromodeoxyuridine （BrdU） and doublecortin （DCX） were used to observe the apoptosis and regeneration of hippocampal neurons.ResultWYJY could improve weight loss in depressed rats. As revealed by the behavioral tests， the model group showed depression-like behaviors， which were relieved in the WYJY groups and the positive drug groups. HE staining showed that the nuclei of hippocampal neurons in the model group were constricted， deeply stained， and sparsely arranged， while the neurons in the WYJY groups and the positive drug groups were significantly improved. Nissl staining demonstrated that the cell density of the model group was lower than that of the normal group （P<0.05）. Compared with model group， the groups with drug intervention showed increased cell density （P<0.05） and compact arrangement. According to the results in TEM， compared with normal group， the model group showed shortened synaptic active zone （P<0.05）， widened synaptic cleft （P<0.05）， and thinned tight zone （P<0.05）. Compared with model group， the groups with drug intervention showed shortened synaptic active zone （P<0.05）， narrowed synaptic cleft （P<0.05）， and thickened tight zone （P<0.05）. As displayed by the results of immunocytochemistry and immunofluorescence， compared with the normal group， the model group showed decreased protein expression of SYP， PSD95， BrdU， and DCX in the hippocampus （P<0.05） and increased protein expression of Caspase-3 （P<0.05）. Compared with the model group， the groups with drug intervention showed increased protein expression of SYP， PSD95， BrdU， and DCX in the hippocampus （P<0.05） and decreased protein expression of Caspase-3 （P<0.05）.ConclusionWYJY can promote the regeneration of hippocampal neurons in rats and improve the depression of rats.
Abstract：ObjectiveTo investigate the molecular mechanism of cordycepin inhibiting proliferation and promoting apoptosis of human hepatoma cells （HCCs）.MethodGlioma-associated oncogene homolog 1 （Gli1） gene was silenced by small interfering RNA （siRNA） and transfected into SMMC-7721 cells， and then cell proliferation was detected by cell counting kit-8 （CCK-8） assay and cell cloning assay. SMMC-7721 cells were treated with different concentration of cordycepin， and the cell proliferation and apoptosis were examined. The expression of Gli1 and the downstream related genes was determined by Real-time polymerase chain reaction（PCR） and Western blot.ResultThe mRNA and protein expression of Gli1 in SMMC-7721 cells was higher than that in normal liver cells （P<0.01）. The proliferation rate of SMMC-7721 with silenced Gli1 decreased at 72 and 96 h （P<0.05， P<0.01）， and the colony-forming capacity lowered （P<0.01） compared with those in the blank group. Compared with the control， 80 μmol·L-1 and 120 μmol·L-1 cordycepin significantly inhibited the proliferation of SMMC-7721 cells at 72 and 96 h （P<0.05， P<0.01）， and promoted the apoptosis of them （P<0.01）. Moreover， 80 and 120 μmol·L-1 cordycepin restrained the mRNA and protein expression of Gli1 in SMMC7721 cells （P<0.05， P<0.01）. At 120 μmol·L-1， cordycepin led to the decrease in the mRNA and protein levels of B-cell lymphoma-2 （Bcl-2） and c-Myc （P<0.05， P<0.01）， and the increase in the mRNA and protein expression of cysteine-aspartic acid protease-3 （Caspase-3） （P<0.05）.ConclusionGli1 is highly expressed in HCCs， and cordycepin can suppress the proliferation and enhance the apoptosis of HCCs by regulating Gli1 and the downstream apoptosis-related factors.
Abstract：ObjectiveTo study the protective effect of total flavonoids of lavender on skin photoaging induced by ultraviolet B （UVB） in mice and to explore its mechanism from the perspective of nuclear factor E2-related factor 2 （Nrf2） antioxidant pathway.MethodEighty-four female KM mice were randomly divided into seven groups， namely blank group， model group， solvent group， vitamin E （0.013 g·kg-1） group， as well as low-， middle-， and high-dose （0.25， 1.25， 2.50 g·kg-1） groups of total flavonoids of lavender. The naked skin on the back of mice was irradiated with UVB for inducing optical damage. Thirty minutes before irradiation， the skin was coated with the total flavonoids of lavender. After continuous irradiation for one week， the skin moisture and elasticity on the back of mice were evaluated， and the effects of total flavonoids of lavender on histopathological changes in mouse skin were investigated by hematoxylin-eosin （HE） and Van Gieson （VG） staining. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， total antioxidant capacity （T-AOC）， nitric oxide synthase （NOS）， and glutathione peroxidase （GSH-Px） after skin homogenization were detected by colorimetry， the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in skin tissue by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of Nrf2， Kelch-like epichlorohydrin-associated protein 1 （Keap1）， BTB-CNC homology 1 （Bach1）， heme oxygenase-1 （HO-1）， quinone oxidoreductase 1 （NQO1）， and glutamate-cysteine ligase catalytic subunit （GCLC） by real-time polymerase chain reaction （Real-time PCR）.ResultCompared with the blank group， the model group exhibited significantly increased appearance score （P<0.01）， reduced skin moisture and elasticity （P<0.01）， pronounced pathological changes in the skin tissue like epidermal thickening， scabbing， small abscess， and severe injury， elevated MDA， NOS， IL-1， IL-6 and TNF-α （P<0.05， P<0.01）， lowered SOD， T-AOC， Nrf2， Keap1， NQO1 and GCLC mRNA expression （P<0.05，P<0.01）， and up-regulated Bach1 mRNA expression （P<0.01）. Compared with the model group， the total flavonoids of lavender at the low， middle， and high doses all remarkably reduced the appearance score （P<0.01）， enhanced the skin moisture and elasticity （P<0.01）， diminished the MDA， NOS， IL-1， IL-6， and TNF-α （P<0.05， P<0.01）， increased SOD， T-AOC， Nrf2， Keap1， NQO1， HO-1 and GCLC mRNA expression （P<0.05， P<0.01）， and down-regulated the expression of Bach1 mRNA （P<0.01）.ConclusionThe protective effect of the total flavonoids of lavender against skin photoaging in mice is significant， which may be related to its activation of Keap1/Nrf2/ARE signaling pathway， regulation of oxidative stress， and improvement of inflammatory response.
Keywords：total flavonoids of lavender;skin photoaging;ultraviolet B （UVB）;Kelch-like epichlorohydrin-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor-2 （Nrf2）/antioxidant response element （ARE） signaling pathway
Abstract：ObjectiveTo explore the molecular mechanism of Yishen Tongluo prescription in inhibiting the apoptosis of glomerular podocytes in rats with membranous nephropathy （MN） based on the miR-514a-5p/tumor necrosis factor superfamily member 15 （TNFSF15） signaling pathway.MethodEighty SD rats were pre-immunized and injected with cationized bovine serum albumin （C-BSA） into the tail vein for inducing MN， and the successfully modeled MN rats were randomly divided into the model group， high-， middle-， and low-dose （26.44， 13.22， 6.61 g·kg-1） Yishen Tongluo prescription groups， and benazepril （10 mg·kg-1） group， with 10 rats in each group， and another 20 healthy rats were classified into the normal group. Rats in each group were gavaged with the corresponding drugs， once a day， for four successive weeks. After the administration， the 24-hour urine total protein （UTP） level， serum total cholesterol （TC）， triglyceride （TG）， albumin （ALB）， creatinine （SCr）， and urea nitrogen （BUN） levels were measured. The miR-514a-5p and TNFSF15 mRNA expression levels in the rat kidney tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the expression levels of podocyte marker proteins Nephrin， Podocin， Podocalyxin， Synaptopodin， TNFSF15， and podocyte apoptosis-related proteins B lymphocytoma-2 （Bcl-2）-related X protein （Bax）， Bcl-2-associated death promoter （BAD） protein， and B-cell lymphoma-extra large （Bcl-XL） by immunohistochemistry （IHC）. Western blot was used to detect the expression levels of TNFSF15， Bax， BAD， Bcl-2， and BCL-XL in the rat kidney tissue. The apoptosis rate of rat kidney tissue was measured using the in situ end labeling method （Tunnel）.ResultCompared with the normal group， the level of miR-514a-5p in the kidney tissue was significantly reduced （P<0.05）， and the TNFSF15 mRNA expression was significantly increased （P<0.05）. The expression levels of podocyte marker proteins Nephrin， Podocin， Podocalyxin， and Synaptopodin were down-regulated （P<0.05）. The protein expression levels of TNFSF15， Bax， and BAD were increased （P<0.05）， whereas the Bcl-2 and Bcl-XL protein expression levels were decreased （P<0.05）. The number of apoptotic cells diminished significantly （P<0.05）. Compared with the model group， the level of miR-514a-5p in the kidney tissue was significantly increased （P<0.05）， while the level of TNFSF15 mRNA was significantly decreased （P<0.05）. The expression levels of podocyte marker proteins Nephrin， Podocin， podocalyxin， and Synaptopodin were up-regulated （P<0.05）， whereas the TNFSF15， Bax， and BAD protein expression levels were down-regulated （P<0.05）. Bcl-2 and Bcl-XL protein expression levels rose （P<0.05）. The number of apoptotic cells significantly decreased （P<0.05）.ConclusionYishen Tongluo prescription reduces the apoptosis of rat kidney podocytes and alleviates the kidney injury of MN rats through the miR-514a-5p/TNFSF15 signaling pathway.
Abstract：ObjectiveTo explore the effect of Wuzhishan Callicarpa nudiflora （LHZZ） on the sensitivity of nasopharyngeal carcinoma （NPC） cells to cisplatin （DDP） and the mechanism.MethodCell counting kit-8 （CCK-8） assay was used to detect the survival rate of NPC HNE1 cells after treatment with different concentration of DDP （0，2，4，8，16，32 mg·L-1） and different concentration of LHZZ （0，25，50，75，100 mg·L-1）. The following groups were designed： control group （normal HNE1 cells），DDP group （8 mg·L-1 DDP，24 h），LHZZ group （50 mg·L-1 LHZZ，24 h），DDP + LHZZ group （8 mg·L-1 DDP + 50 mg·L-1 LHZZ，24 h），DDP + LHZZ + nuclear factor erythroid 2-related factor 2 （Nrf2） activator sulforaphane （SFN） group （8 mg·L-1 DDP + 50 mg·L-1 LHZZ，24 h， 10 μmol·L-1 SFN，24 h）. Then CCK-8 assay was employed to examine cell survival rate，colony formation test the colony-forming ability，flow cytometry and in situ terminal end-labeling（TUNEL） staining cell apoptosis，fluorescent probe 2'，7'-dichlorofluorescin diacetate （DCFH-DA） the level of reactive oxygen species （ROS） in cultured cells，Western blot the expression of apoptosis-related proteins in cells，such as B-cell lymphoma/leukemia-2 （Bcl-2），Bcl-2 associated X protein （Bax），and cysteinyl aspartate specific proteinase-3 （Caspase-3），and Real-time quantitative polymerase chain reaction （Real-time PCR） the expression of Nrf2 and antioxidant response element （ARE） mRNA in cells.ResultThe survival rates of cells treated with different concentration of DDP and different concentration of LHZZ decreased compared with that in the control group （P<0.05）. Compared with the DDP group and the LHZZ group，DDP + LHZZ group demonstrated decrease in cell survival rate，number of cell colonies，and Bcl-2 level，and increase in the apoptosis level and the expression of Bax and Caspase-3 （P<0.05）. However，after the addition of SFN，the Nrf2/ARE signaling pathway was activated and the above variation was inhibited （P<0.05）. In addition，the level of intracellular ROS in the LHZZ group was lower than that in the control group （P<0.05） and the level in the DDP + LHZZ group was lower than that in the DDP group （P<0.05）. Moreover，the ROS level in the DDP + LHZZ + SFN group was higher than that in the DDP+LHZZ group （P<0.05）.ConclusionLHZZ can enhance the sensitivity of DDP-induced NPC apoptosis，possibly by blocking the Nrf2/ARE signaling pathway and inhibiting the level of ROS.
Keywords：nasopharyngeal carcinoma;cisplatin;Wuzhishan Callicarpa nudiflora in Hainan province;apoptosis;sensitivity
Abstract：ObjectiveTo explore the structural characteristics and functional differences of intestinal flora in patients with type 2 diabetes mellitus （T2DM） of dampness heat trapping spleen（DHTS） syndrome and Qi-Yin deficiency（QYD） syndrome.MethodFrom June 2018 to January 2020，62 T2DM patients with DHTS syndrome and 60 with QYD syndrome were selected from Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Serum and fecal samples were collected to compare body mass index（BMI），glucose and lipid metabolism，fasting insulin （FINS） and fasting C-peptide （FCP） levels，and homeostasis model assessment of insulin resistance（HOMA-IR） of the two syndrome types. Fecal samples were extracted for DNA database construction，and 16S rDNA high-throughput sequencing was used to analyze and compare the intestinal flora and metabolic pathways.Result① The BMI，fasting plasma glucose（FPG），2-hour postprandial blood glucose （2 h PBG），total cholesterol（TC），triglyceride（TG），low density lipoprotein（LDL），FINS，FCP，and HOMA-IR were higher in patients with DHTS syndrome than in patients with QYD syndrome，and the high density lipoprotein（HDL） of the former was lower than that of the latter，（P<0.05，P<0.01）. ② In terms of species composition and differences，Bacteroidetes， Clostridia and Gammaproteobacteria were dominant at the class level，and the relative abundance of Clostridia，Mollicutes and Verrucomicrobiae in QYD syndrome group was higher than that in DHTS syndrome group. At the order level，Bacteroidales，Clostridiales and Enterobacteriales were mainly found. The relative abundance of Clostridiales，Erysipelotrichales and Verrucomicrobiales in QYD syndrome group was obviously higher than that in DHTS syndrome group，while Aeromonadales in the former was lower than that in the latter （P<0.05）. At the family level，Bacteroidaceae，Prevotellaceae and Ruminococcaceae were predominant. The relative abundance of Ruminococcaceae，Porphyromonadaceae and Erysipelotrichaceae in QYD syndrome group was higher than that in DHTS syndrome group（P<0.05）. At the genus level，Bacteroides，Prevotella and Parabacteroides were mainly found. The relative abundance of Parabacteroides，Butyrivibrio and Ruminiclostridium in QYD syndrome group was higher than that in DHTS syndrome group，while that of Klebsiella and Megasphaera in DHTS syndrome group was higher than that in QYD syndrome group（P<0.05）. ③ Through Venn analysis of operational taxonomic units（OTU），it was found that there were 49 OTUs in patients with DHTS syndrome patients and 47 OTUs in QYD syndrome patients. ④ The results of OTU β diversity and α analysis showed that Shannon and Simpson indexes had statistical differences，while Ace and Chao indexes had no statistical differences. The intestinal microbial diversity of patients with QYD syndrome was higher than that of patients with DHTS syndrome（P<0.05）. The analysis of similarities （ANOSIM） showed that the difference of β diversity between the two groups was significant（P<0.05）. ⑤ Linear discriminant analysis Effect Size（LEfSe） results demonstrated that Klebsiella，Megasphaera and Aeromonadales could be selected as the key biomarkers for DHTS syndrome； 14 bacteria such as Ruminiclostridium，Burkholderiaceae，Lautropia，Butyrivibrio，Erysipelotrichales can be selected as the key biomarkers for QYD syndrome. ⑥Functional annotation and analysis showed that the DHTS syndrome involved 9 metabolic pathways，including arginine and proline metabolism，lipopolysaccharide biosynthesis，nicotinic acid and nicotinamide metabolism，while the QYD syndrome involved 10 metabolic pathways，including acarbose and valinomycin biosynthesis，glucagon signaling pathway and NOD-like receptor signaling pathway.ConclusionThere are obvious differences in intestinal flora and functions in T2DM patients of DHTS syndrome and QYD syndrome，which can be used as reference for traditional Chinese medicine （TCM） syndrome differentiation and the target of TCM treatment.
Abstract：ObjectiveTo observe the clinical efficacy and anti-inflammatory and anti-oxidant effect of modified Guipitang combined with Xuefu Zhuyutang in the treatment of mild cognitive impairment （MCI） after cerebral infarction with syndromes of heart and spleen deficiency and blood stasis blocking collateral.MethodA total of 114 eligible patients were randomly divided into a control group and an observation group，with 57 cases in each group. Patients in the control group were given red deer ginseng tablets （po），4 tablets/time，2 times/day. Patients in the observation group were given modified Guipitang combined with Xuefu Zhuyutang （po，1 dose/day）for continuous 8 weeks. This study compared the scores of montreal cognitive assessment （MoCA） scale，Rivermead behavioral memory test （RBMT），activities of daily living （ADL），trail making test B （TMT-B），neuropsychiatric inventory questionnaire （NPI） and scores of traditional Chinese medcine（TCM） syndrome with syndromes of heart and spleen deficiency and blood stasis blocking collateral before and after treatment. Then we further detected the levels of 8-hydroxydeoxyguanosine （8-OHDG），malondialdehyde （MDA），oxidized low density lipoprotein （ox-LDL），superoxide dismutase （SOD），homocysteine （Hcy），interleukin-8 （IL-8），C-reactive protein （CRP） and fibrinogen （FIB） levels before and after treatment.ResultThe total effective rate for the treatment of cognitive function impairment in the observation group was 92.98% （53/57），which was higher than 78.95% （45/57） in the control group （χ2＝4.653，P<0.05）. The recovery rate of cognitive function in the observation group was 54.39% （31/57），which was higher than 33.33% （19/57） in the control group （χ2＝5.130，P<0.05）. The MoCA，RBMT and ADL scores of the observation group were higher than those of the control group （P<0.01），and the TMT-B time of the former was shorter than that of the latter （P<0.01）. In addition， the observation group showed lower scores of TCM syndrome，NPI-1 and NPI-2 scores than the control group （P<0.01）. The SOD level of the observation group was higher than that of the control group （P<0.01），and the levels of 8-OHDG，ox-LDL，MDA，Hcy，IL-8，CRP and FIB were lower than those of the control group （P<0.01）.ConclusionModified Guipitang combined with Xuefu Zhuyutang can improve cognitive function in MCI patients after cerebral infarction with syndromes of heart and spleen deficiency and blood stasis blocking collateral， with anti-inflammatory and anti-oxidant effect， and yield superior efficacy than red deer ginseng tablets.
Keywords：mild cognitive impairment;cerebral infarction;deficiency of both heart and spleen，blood stasis blocking collateral syndrome;Guipitang;Xuefu Zhuyutang;inflammatory factor;oxidative stress
Abstract：ObjectiveTo study the effect of Shenling Baizhusan on electrogastrogram in children with spleen deficiency diarrhea. To clarify the occurrence of gastric electrical rhythm disorder in children with this disease， and to study whether Shenling Baizhusan can improve the abnormal gastric motility in children with diarrhea （spleen deficiency）MethodA total of 125 children with spleen deficiency diarrhea in the outpatient department of Children's Hospital of Shanghai from October 2019 to March 2021 were selected as the research objects， and they were randomly divided into a control group （60 cases） and an observation group （65 cases）. The children in the control group were treated with Montmorillonite powder combined with probiotics treatment， and the children in the observation group were additionally treated with Shenling Baizhusan. The course of treatment for both groups was 1 week. The clinical efficacy of the two groups of children after treatment and the scores of main traditional Chinese medcine（TCM） symptoms before and after treatment were compared， and the changes in the main parameters of electrogastrogram in children before and after treatment were compared.ResultAfter treatment， the total effective rate of observation group （90.77%， 59/65） was higher than that of control group （76.67%，46/60） （χ2=4.617， P<0.05）. After treatment， scores of fecal morphology， frequency of defecation， fatigue， inappetence， and other symptoms in both groups were lower than that before treatment （P<0.05）， and the observation group was lower than the control group （P<0.05）. As compared with before treatment， the main frequency， the percentage of normal slow wave， and the percentage of normal gastric electrical rhythm in the two groups increased after treatment （P<0.05）， and the control group was lower than the observation group （P<0.05）. The proportion of children with slow gastric rhythm decreased （P<0.05） as compared with before treatment， and the control group was higher than the observation group （P<0.05）.ConclusionShenling Baizhusan can significantly relieve the diarrhea symptoms in children with spleen deficiency diarrhea and improve gastric motility with good clinical effects.
Abstract：ObjectiveTo develop a quantitative analysis of multi-components by single marker （QAMS） for determination of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills， and to provide a method for improving the national standard of the pills.MethodHigh performance liquid chromatography （HPLC） was developed for simultaneous determination of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills and the methodology validation was carried out. The chromatographic separation was performed on a Nucleosil 100-5 C18 column （4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile -0.1% potassium dihydrogen phosphate aqueous solution （pH adjusted to 3.2 with phosphoric acid） （48∶52）， and the flow rate was 0.6 mL·min-1， the detection wavelength was set at 296 nm and the column temperature was 35 ℃. Taking cinobufagin as the internal standard， the relative correction factors （RCFs） of bufalin and resibufogenin were calculated， and the key influencing factors of RCFs were investigated. Relative retention time was used for the chromatographic peak location of the analyte， combining with the on-line ultraviolet spectroscopy and accurate relative molecular weight obtained by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-QTOF/MS）. The external standard method was used to verify the contents of three components obtained by QAMS.ResultQAMS was established for the determination of bufalin， cinobufagin and resibufogenin in the samples， and RCFs of cinobufagin to bufalin and resibufogenin were 0.922 and 1.01， respectively. The total content of the three marker compounds in 11 batches of Shexiang Baoxin pills was 33.7-36.0 µg per pill. There was no significant difference between the quantitative results of QAMS and external standard method.ConclusionThe established method can be used for the quality control of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills. It is suggested that bufalin should be considered as one of three marker compounds， and the sum of bufalin， cinobufagin and resibufogenin should be used for the content limit of this preparation.
Keywords：Bufonis Venenum;Shexiang Baoxin pills;cinobufagin;bufalin;resibufogenin;quantitative analysis of multi-components by single marker （QAMS）;high performance liquid chromatography （HPLC）
Abstract：ObjectiveTo study the effects of different plant growth-promoting rhizobacteria （PGPR） on the growth of Paris polyphylla var. yunnanensis seedlings and the quality of its medicinal parts， in order to provide reference for the cultivation of high-quality P. polyphylla var. yunnanensis.MethodThe pot culture experiment at room temperature and the single-factor completely random design were employed for exploring the effects of five PGPR on physiological characteristics and inorganic elements of P. polyphylla var. yunnanensis.ResultThe results showed that the exogenous inoculation of different PGPR promoted the growth and development of P. polyphylla var. yunnanensis to varying degrees， delayed the senescence of leaves， and improved the medicinal value of new and old rhizomes. Compared with the non-inoculated control， the exogenous inoculation of compound microbial fertilizer （FH） and microbial agent Sanju Guanjin liquid （SJ） enhanced the root vigor， increased the content of photosynthetic pigments and the activities of anti-oxidant enzymes ［superoxide dismutase （SOD）， catalase （CAT）， and peroxidase （POD）］， and reduced the content of malondialdehyde （MDA） in leaves. Their inhibition rates against MDA were 10.46%-39.62% and 20.99%-53.12%， respectively. With the growth of P. polyphylla var. yunnanensis， the inhibition rate against MDA gradually increased， which effectively delayed the senescence of P. polyphylla var. yunnanensis leaves. In addition， the exogenous inoculation of different PGPR promoted the accumulation of nutrient elements in new and old rhizomes， lowered the heavy metal content to varying degrees， and improved the medicinal value of P. polyphylla var. yunnanensis rhizomes.ConclusionFH and SJ have exhibited the best promoting effect on the growth of P. polyphylla var. yunnanensis seedlings and also the best regulatory effect on the medicinal value of P. polyphylla var. yunnanensis rhizomes， which has provided reference for the application and promotion of PGPR in the growth of P. polyphylla var. yunnanensis.
Keywords：Paris polyphylla var. yunnanensis;plant growth-promoting rhizobacteria （PGPR）;physiological characteristics;nutrient;heavy metal elements
Abstract：ObjectiveTo improve the current standard of Belladonnae Herba in the 2020 edition of Chinese Pharmacopoeia.MethodTaking hyoscyamine sulfate， atropine sulfate and scopoletin as reference substances， and ethyl acetate-methanol-concentrated ammonia（17∶4∶2）as developing solvent， thin layer chromatography （TLC） was applied in the qualitative identification of Belladonnae Herba. The moisture， total ash and ethanol-soluble extract of Belladonnae Herba were determined based on the general principles in the 2020 edition of Chinese Pharmacopoeia （volume Ⅳ）. The contents of hyoscyamine sulfate and scopolamine hydrobromide were analyzed by high performance liquid chromatography （HPLC） with mobile phase of acetonitrile-54 mmol·L-1 phosphate buffer solution （14∶86）， flow rate of 1.0 mL·min-1 and detection wavelength at 210 nm.ResultThe spots in the TLC were clear with good separation and specificity. Hyoscyamine sulfate and scopolamine hydrobromide showed a good linearity with peak area in the range of 0.024 7-0.789 6 g·L-1 （r=0.999 9） and 0.003 9-0.124 0 g·L-1 （r=0.999 9）， the average recoveries of these two ingredients were 100.29% （RSD 1.6%） and 99.04% （RSD 1.4%）， respectively. The limits for moisture， total ash in Belladonnae Herba should be less than 13.0% and the limit for the ethanol-soluble extract should be more than 10.0%. Due to the low content and wide variation of scopolamine hydrobromide， the content of hyoscyamine sulfate should not be less than 0.098%.ConclusionThe established method is simple， specific and reproducible， which can be used to improve the quality control standard of Belladonnae Herba.
Abstract：ObjectiveTo develop safe and effective microbial agents against Panax ginseng root rot.MethodP. notoginseng endophytes were screened in plate confrontation tests， followed by morphological and molecular biological identification of antagonistic strains， optimization of strain fermentation conditions in a single factor test， and determination of optimal carriers and auxiliary agents of the microbial agent and their ratio using response surface methodology for formulating the production process. The prevention and control effects of the microbial agent were verified in the confrontation and pot culture experiments.ResultThe plate confrontation test yielded a strain named Fusarium pseudoanthophilum with significant resistance to root rot， and its antibacterial rate was 53.33%. According to the single factor test， the fermentation conditions of F. pseudoanthophilum were determined to be fermentation time 60 h， fermentation temperature 26 ℃， speed 120 r·min-1， and pH 6.5. The response surface optimization results showed that the number of viable bacteria reached the maximum （5.23×109 cfu·g-1） when the peat was 60.00 g， sodium carboxymethylcellulose 3.50 g， and sodium alginate 4.76 g. The influences of carriers and auxiliary agents on the number of viable bacteria were sorted by degree in a descending order as follows： peat>sodium carboxymethylcellulose >sodium alginate. The confrontation test results showed that when the microbial agent concentration was greater than 1.00 g·L-1， it had a significant inhibitory effect on the root rot pathogen F. oxysporum and the inhibitory rate was more than 42.3%. As demonstrated by the pot culture experiment， the inoculation of biocontrol agent for 28 d significantly reduced the incidence （66.99%） of root rot in P. ginseng seedlings and disease index （61.69%） and increased their leaf length （33.04%） and fresh weight （34.48%）.ConclusionF. pseudoanthophilum inoculant is efficient in preventing and controlling the root rot， making it worthy of further development and utilization.
Abstract：ObjectiveTo explore the effect of Buyang Huanwutang （BHD） on rehabilitation of ischemic stroke（IS） by cell membrane solid-phase chromatography and network pharmacology.MethodCell membrane solid-phase chromatography was performed to screen the specific binding components of BHD with hippocampal neurons. Targets of the specific components were retrieved based on PubChem and PharmMapper and those of IS were searched from Online Mendelian Inheritance in Man （OMIM） and GeneCards. Then， the protein-protein interaction （PPI） network was constructed with STRING and Cytoscape 3.7.1， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the hub genes in the PPI network. Thereby， the mechanism of BHD in promoting IS rehabilitation was clarified.ResultA total of 13 specific components were identified. The hub genes were mainly involved in the biological processes of regulation of cell proliferation， protein phosphorylation， hypoxia response， and angiogenesis， and the pathways of Forkhead box O （FoxO） signaling pathway， adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK） signaling pathway， nuclear factor kappa B （NF-κB） signaling pathway， and apoptosis pathway.ConclusionBHD may promote the recovery of IS by regulating FoxO， AMPK， NF-κB， and apoptosis pathways.
Abstract：ObjectiveTo investigate the compatibility rule of traditional Chinese patent medicines （TCPMs） against liver diseases through network analysis.MethodWith “liver” as the search term， TCPMs against liver diseases were retrieved from volume Ⅰ of Chinese Pharmacopoeia （2020 edition）， and the basic information of them was collected. TCPMs with same Chinese medicinal materials （CMMs）， usage， and indications， but different dosage forms， were unified as one formula. Mutual information entropy （MIE） of CMM couples was calculated to quantify the relationship between them， and the top 25% CMM pairs in MIE were used to construct the compatibility network， with CMM as node and the relationship between CMM pairs as the edge. Key CMM and frequently used CMM combinations were identified based on node centrality and cluster analysis， respectively. The indications of TCPMs related to the CMMs in clusters were recorded. Cytoscape 3.6.1 was employed for visualization and topology analysis of the compatibility network.ResultA total of 179 TCPMs， involving 428 CMMs， were retrieved. Angelicae Sinensis Radix， Paeoniae Radix Alba， and Glycyrrhizae Radix et Rhizoma were identified as key CMMs with high frequency， and Cuscutae Semen-Lycii Fructus， Citri Reticulatae Pericarpium-Cyperi Rhizoma， and Ecliptae Herba-Ligustri Lucidi Fructus combinations had high MIE. Furthermore， the CMMs were clustered into ten groups corresponding to different diseases which， however， all belonged to digestive diseases.ConclusionThis study unveils potential CMM pairs and common CMM combinations against liver diseases， which can serve as a reference for revealing compatibility rules of CMMs and research and development of Chinese medicine.
Keywords：Chinese Pharmacopoeia;liver disease;traditional Chinese patent medicines;mutual information entropy;compatibility network
Abstract：ObjectiveTo explore the mechanism of Xueniao capsule in the treatment of acute pyelonephritis （APN） by network pharmacology and experimental verification.MethodThe effect of Xueniao capsule on APN was investigated based on the APN model in rats. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Chemistryl Database， and SymMap were searched for the chemical components of Smilacis Chinae Rhizoma，Coicis Semen， and Trachycarpi Petiolus. The target information of the components was collected from PharmMapper and SwissTargetPrediction， and disease target information from Therapeutic Target Database （TTD）， DrugBank， DisGeNET， GeneCards， and Online Mendelian Inheritance in Man（OMIM）. The key genes of Xueniao capsule for APN underwent Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses by Metascap. Real-time quantitative polymerase chain reaction （PCR） and Western blot were employed to verify the prediction results.ResultCompared with the blank group and the sham operation group， the model group showed an increased ratio of the left kidney to the right kidney and organ index（P<0.05， P<0.01），up-regulated white blood cells （WBC），neutrophils （NEUT），monocytes （MONO）， and lymphocytes （LY）（P<0.05， P<0.01）， and elevated levels of nuclear factor-κB（NF-κB）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）（P<0.05， P<0.01）. Compared with the model group， the norfloxacin group， the low- and high-dose Xueniao capsule groups showed a decreased ratio of the left kidney to the right kidney and organ index（P<0.05， P<0.01）， dwindled levels of WBC， NEUT， MONO， and LY（P<0.05， P<0.01）， and reduced levels of NF-κB， IL-6， and TNF-α（P<0.05， P<0.01）. The medium-dose Xueniao capsule group showed a decreased ratio of the left kidney to the right kidney and organ index（P<0.05， P<0.01）， reduced levels of WBC， NEUT， MONO， and LY（P<0.05， P<0.01）， and dwindled levels of IL-6 and TNF-α（P<0.05， P<0.01）. Network pharmacological analysis revealed 17 active compounds from Smilacis Chinae Rhizoma， 18 active compounds from Coicis Semen， six active compounds from Trachycarpi Petiolus， and 39 key genes for the treatment of APN in Xueniao capsule. GO enrichment analysis demonstrated 704 biological processes， 22 cellular components， and 59 molecular functions. Sixty-two pathways were enriched in KEGG enrichment analysis. The experimental verification results showed that compared with the blank group， the model group showed increased mRNA expression of prostaglandin-endoperoxide synthase 2 （PTGS2）， mitogen-activated protein kinase 1 （MAPK1）/extracellular signal-regulated protein kinase 2 （ERK2），phosphoinositide 3 kinase （PI3K），protein kinase B2（Akt2），Janus kinase 2 （JAK2），and signal transducer and activator of transcription 3 （STAT3）and protein expression of PI3K， Akt2， JAK2， and STAT3 （P<0.05， P<0.01）. Compared with the model group， the low-dose Xueniao capsule group showed decreased mRNA expression of MAPK1， PI3K， JAK2， and STAT3 and protein expression of PI3K， JAK2， and STAT3 （P<0.05， P<0.01）. The medium-dose Xueniao capsule group showed decreased mRNA expression of MAPK1， PTGS2， PI3K， JAK2， and STAT3， and protein expression of PI3K， JAK2， and STAT3 （P<0.05， P<0.01）. The high-dose Xueniao capsule group showed reduced mRNA expression of PTGS2， MAPK1， PI3K， Akt2， JAK2， and STAT3 and protein expression of PI3K， Akt2， JAK2， and STAT3 （P<0.05， P<0.01）.ConclusionXueniao capsule has a certain curative effect on APN via multiple targets and multiple pathways. The mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and the JAK2/STAT3 signaling pathway.
Abstract：China Association of Chinese Medicine organized specialists in andrology of Chinese and western medicine to explore the population and treatment stage of benign prostatic hyperplasia （BPH） with Chinese medicine as the leading therapy. Chinese medicine has great advantages in the treatment of benign prostatic hyperplasia. However， it is necessary to make clear the stage when Chinese medicine or modern medical treatment can be used as the leading therapy， and the conditions under which Chinese and western medicine can be combined to achieve the best treatment efficacy. The specialists agreed Chinese medicine as the leading therapy for the treatment of BPH in the following populations or conditions： the elderly and weak patients with basic diseases， BPH symptoms， and cannot tolerate anesthesia and surgery， the patients with BPH symptoms and cannot tolerate the adverse reactions or the possible adverse reactions of western medicine； the patients with mild ［international prostatic symptom score （IPSS） ≤ 7］ or moderate lower urinary tract symptoms （IPSS ≥ 8） and the quality of life not significantly affected， the patients with bladder detrusor hypofunction， bladder dysfunction and cannot be treated surgically， or with incomplete bladder emptying after surgical treatment； the BPH patients with prostatitis as the main clinical manifestation， the patients with non-acute complications after operation. BPH is one of the dominant diseases in urology and andrology of Chinese medicine， and the symptoms， complications， and prognosis of BPH patients need to be fully considered during the clinical treatment. When Chinese medicine is taken as the leading therapy， it is essential to regularly review the serum level of prostate-specific antigen to exclude the possibility of prostate cancer， and apply Chinese medicine for full treatment course and cycle. At the same time， Chinese and western medicine can be combined to achieve the most effective， convenient， economical， and satisfactory treatment， which can carry forward the advantages of Chinese medicine in treating this disease.
Keywords：benign prostatic hyperplasia;dominant diseases;treatment led by Chinese medicine
Abstract：Benign prostatic hyperplasia （BPH） model， as a carrier of BPH， is vital for exploring the pathogenesis of the disease and evaluating the efficacy of corresponding drugs. This paper reviewed the in vivo and in vitro models of BPH， the modeling principles and methods， and evaluation indicators， and analyzed the advantages and disadvantages of different types of models. At present， the BPH model is getting closer to the clinical characteristics of human BPH， providing powerful support for the evaluation of drug efficacy. Furthermore， the model has been developed towards cytology to allow further research on the pathogenesis of BPH. The relevant testing indicators reflect the core pathological changes of BPH from different levels， providing a guarantee for further exploring the pathogenesis of BPH and the development of prevention and control drugs. However， no model can fully simulate the natural development process of human BPH， and each model and evaluation criterion has its unique advantages and limitations. In terms of model evaluation， most BPH models are assessed based on benign prostate enlargement （BPE）， and there is still a lack of reliable models to simulate BPH progression and combine with bladder dysfunction. In terms of indicator evaluation， symptom-reflected behavioral indicators are absent in the replication of BPH models in animals. The study of the BPH model in traditional Chinese medicine （TCM） only focuses on the replication and investigation of the "disease" model， rather than the "syndromes" and "signs"， which cannot simulate the syndrome differentiation and treatment under the guidance of the TCM theory. In view of the above deficiencies， we should further improve the modeling method based on clinical characteristics， explore the multifactor composite models， especially those of disease-syndrome combination suitable for basic research of TCM， replicate the model closing to disease development， and optimize the evaluation indicators， which is of great theoretical and practical significance to develop drugs for effective prevention and control of BPH.
Abstract：Benign prostatic hyperplasia （BPH）， a common disease in urology and andrology， is mainly manifested as enlarged prostate glands， bladder outlet obstruction， and lower urinary tract symptoms（LUTS）， which seriously affects the quality of life of middle-aged and elderly men. This disease falls into the categories of "retention of urine" and "prostatic hypertrophy" in traditional Chinese medicine （TCM）. In recent years，many doctors have put forward their understandings of BPH based on academic classics and their clinical experience. Clinical research on the treatment of BPH with TCM has become increasingly abundant. The basic pathogenesis of BPH lies in the disturbance of Qi transformation in the bladder and poor blood circulation due to kidney Qi deficiency in the aged. The disease is located in the kidney and the bladder and is related to the dysfunction of the lung and the kidney. It is basically characterized by deficiency in origin and excess in superficiality. A large number of clinical research reports have proved that TCM is efficient in alleviating the clinical symptoms of BPH patients， improving their quality of life， reducing the volume of the prostate， and decreasing postoperative complications. In addition， the external treatment methods of TCM， such as acupuncture therapy， moxibustion， hot water bathing， acupoint application， anal suppository， and enema therapy， are also widely used in clinical practice， demonstrating the diverse ways of TCM in treating BPH. TCM and western medicine complement each other's advantages in the treatment of BPH， thus enhancing the clinical efficacy and reducing the occurrence of long-term complications. This study reviewed the etiology， pathogenesis， and treatment progress of BPH with TCM in recent years， and summarized the current research status. From three aspects of producing high-quality clinical research， standardizing the clinical diagnosis and treatment of TCM， and combining cutting-edge research to explore the mechanism of TCM， it provided suggestions for clinical research on the treatment of BPH with TCM to promote the development and application of TCM in the treatment of this disease.
Keywords：benign prostatic hyperplasia （BPH）;traditional Chinese medicine （TCM）;etiology and pathogenesis;clinical research;review
Abstract：This study systematically combed and analyzed the use of such terms as "prohibition"， "contraindication"， and "use with caution" in ancient Chinese books on materia medica and prescriptions， Pharmacopoeia of the People's Republic of China（《中华人民共和国药典》）， and teaching materials and monographs of Chinese materia medica by means of hermeneutics， commentariology， textology， and data mining， and explored the historical evolution and conceptual connotations of "prohibition"， "contraindication"， and "use with caution" in Chinese materia medica， so as to provide reference for standardizing their understandings and clinical reasonable medication. The "prohibition"， "contraindication"， and "use with caution" of Chinese materia medica were first proposed in the period of pre-Qin and Han dynasties. "Prohibition" and "contraindication" were separately developed in the Sui， Tang， and Five dynasties and Song， Jin， and Yuan dynasties and have been widely used since the Ming and Qing dynasties. The "use with caution" becomes popular rapidly in modern times and is often present in clinical medication together with "prohibition" and "contraindication". "Prohibition" basically means strictly prohibited and "contraindication" means to avoid as much as possible. The terms "prohibition"， "contraindication"， and "use with caution" have experienced evolution from the pre-Qin period to modern times， and they are used to describe the degree of restriction on drug use（"prohibition" > " contraindication" > "use with caution"）.
Keywords："prohibition， contraindication， and use with caution";terms describing restrictions on drug use;Chinese materia medica;historical evolution;connotation
Abstract：The morbidity and mortality of cancer have been on the rise， making it atop the list of human health threats. It has been a conundrum of global magnitude. As the side effects of chemotherapeutics seriously affect the life quality of cancer patients， it is urgent to find effective anti-cancer drugs with small toxic and side effects. In recent years， the anti-cancer effects of traditional Chinese medicine have attracted the interest of scholars. Owing to the improvement of medical research， an increasing number of anti-cancer components with small toxic and side effects have been extracted from traditional Chinese medicine. Rutin， a unique flavonoid in Chinese medicinals and many plants， proves to inhibit the proliferation of breast cancer， colon cancer， lung cancer， and prostate cancer cells. In addition， rutin alone or in combination with other therapeutic drugs can regulate a variety of signaling pathways and signal mediators of inflammation， apoptosis， autophagy， and angiogenesis， thereby suppressing tumor progression. Moreover， it can also alleviate the drug resistance of tumors and the side effect of chemotherapeutics. Nevertheless， it is limited by the low bioavailability and low solubility， to which nano delivery system turns to be a solution. At the moment， the anti-cancer potential of rutin and the molecular targets of it against various cancers have not been summarized and comprehensively analyzed. Therefore， the authors retrieved articles on the anti-cancer effects of rutin in recent years， summed up the mechanisms and molecular targets， and discussed relevant drug delivery systems and the safety， aiming at laying a theoretical foundation for further development and application of the flavonoid.
Abstract：Diabetic cardiomyopathy， one of the cardiovascular complications of diabetes， is characterized by cardiac systolic and diastolic dysfunction at the early stage， which can later develop into heart failure. Due to the high incidence and mortality， it has been a hot topic in recent years. The pathogenesis of diabetic cardiomyopathy is complicated. It has been proved related to abnormal glucose and lipid metabolism， cardiac insulin resistance， mitochondrial dysfunction， abnormal calcium homeostasis， activation of renin-angiotensin-aldosterone system， increased oxidative stress， endoplasmic reticulum stress， inflammation， autophagy， and so on. The specific pathogenesis remains unclear. Currently， the diabetic cardiomyopathy is mainly tackled with both western medicine and traditional Chinese medicine （TCM）. Traditional western medicine has no specific remedy for diabetic cardiomyopathy， and the resulting side effect cannot be neglected. In order to improve the efficacy and reduce the side effects， researchers have tried some potential medical treatments， such as vaspin， melatonin， Coenzyme Q10， and non-coding RNA， which still need further clinical trials. Diabetic cardiomyopathy is not recorded in ancient TCM books. According to the symptoms and signs， modern physicians often consider it as a "consumptive disease"， whose main therapeutic principles lie in benefiting Qi， tonifying Yin， activating blood， and removing stasis. The individual Chinese herbs such as Astragali Radix and Salviae Miltiorrhizae Radix et Rhizoma and Chinese herbal compounds like Huotan Jiedu Tongluoyin are effective in protecting the heart. But there are few studies exploring the pharmacodynamic mechanisms of TCM. With the continuous emergence of new drugs， the integration of TCM with western medicine may be a more promising treatment in the future. In conclusion， the pathogenesis of diabetic cardiomyopathy is unclear， and there is a lack of effective prevention and treatment. This paper reviewed the latest findings in pathogenesis and treatment of diabetic cardiomyopathy， in order to provide reference for further research.
Abstract：Diabetes and depression are both incurable chronic diseases， which are complementary and integrated. They are clinically called diabetic depression. A large number of epidemiological and clinical studies have confirmed that diabetes interacts with depression， leading to complex conditions of diabetic depression， difficult treatment， and poor prognosis. Diabetes and depression are considered two independent diseases in the majority of the existing clinical methods for the treatment of diabetic depression， with many defects such as low efficiency and severe side effects. Traditional Chinese medicine （TCM） treatment of diabetic depression， characterized by multiple targets， multiple pathways， and overall coordination， can adjust the synergy between multiple systems of the body and is advantageous in the treatment of diabetic depression. However， the evaluation of the efficacy of TCM in the treatment of diabetic depression is mostly limited to the improvement of clinical symptoms， the control of blood sugar level， and the score of depression scale， and there is a lack of in-depth research on the mechanism of action. Therefore， many researchers are devoted to exploring the underlying mechanism of TCM in the treatment of diabetes combined with depression. Clarifying the comorbidity mechanism is the key in treating diabetic depression. In this study， we made an introduction according to the mechanism based on the relevant research reports on the treatment of diabetic depression with TCM and summarized its specific mechanisms， including insulin resistance， oxidative stress and inflammation， and nervous system disorder. The interaction between the various mechanisms has further aggravated the complexity of diabetic depression. We have drawn a diagram of the mechanism pathways of diabetic depression in order to provide new ideas for clinical diagnosis and treatment.
Keywords：diabetes;depression;comorbidity mechanism;Chinese medicinal compound;external treatment of traditional Chinese medicine
Abstract：Rehmanniae Radix is a common medicine of traditional Chinese medicine， which has the function of nourishing Yin and tonifying the kidney， and has a long application history of processing. This medicine was first recorded in Synopsis of Golden Chamber （《金匮要略》）， which was mainly produced by steaming and boiling. Its processing materials were diverse. In addition to rice wine， honey， Amomi Fructus， milk， Aquilariae Lignum Resinatum， and Carthami Flos were also recorded in ancient books， but with the evolution of time， the characteristic excipients gradually disappeared. Based on this， starting with different excipients， the author consulted the classics of materia medica and processing specifications in various regions， sorted out the historical evolution of Rehmanniae Radix processing， and explored new methods and new ideas to exert the maximum efficacy on this basis. At the same time， the effects of different processing excipients on the chemical components and pharmacodynamic effects of Rehmanniae Radix were analyzed. After literature review， it was found that Rehmanniae Radix mainly had the effects of clearing heat and cooling blood， nourishing Yin and generating fluid. Its traditional processing excipients generally used rice wine， Carthami Flos and others. After processing with different excipients， there was different effects on the chemical components and pharmacological effects of Rehmanniae Radix. In summary， this paper can provide useful reference for standardized research on different processed products of Rehmanniae Radix.