Abstract：ObjectiveTo observe the effect of Shaoyaotang on the contents of cell adhesion molecule-1 （ICAM-1） and transforming growth factor-β1 （TGF-β1） in serum of large intestine damp-heat syndrome of ulcerative colitis （UC） in rats， and the gene and protein expressions of leukocyte differentiation antigen14 （CD14）， Fas-related death domain protein （FADD） and cysteinyl aspartate specific protease-8 （Caspase-8） in the focal colon tissue.MethodA total of 80 SPF Wistar rats were randomly divided into the blank group （n=10） and modeling group （n=70）. The large intestine damp-heat syndrome of UC rats was replicated by the combination of disease and syndrome， which was high-fat， high-sugar and spicy diets combined with 2， 4-dinitrobenzene sulfonic acid （DNBS） and ethanol. After successful modeling， the modeled groups were divided into model group， sulfasalazine （SASP）control group， and low， medium and high-dose Shaoyaotang groups by the method of random number table， with14 rats in each group. Low， medium and high doses of Sulfasalazine 0.2 g·kg-1·d-1 and Shaoyaotang （6， 12， 24 g·kg-1·d-1）were given by gavage. The blank group and the model group were given equal volume of normal saline for 21 days. The contents of serum ICAM-1 and TGF-β1 were detected by enzyme-linked immunosorbent assay （ELISA）， the expressions of CD14， FADD and Caspase-8 mRNA in colon tissues were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the expressions of CD14， FADD and Caspase-8 protein in colon tissues were detected by Western blot.ResultCompared with the blank group， the serum ICAM-1 level in the model group were significantly increased， whereas the content of TGF-β1 were significantly decreased （P<0.05）. The relative expression levels of CD14， FADD， Caspase-8 mRNA and protein were significantly increased （P<0.05）. Compared with the model group， the content of ICAM-1 in the serum of the rats in the medium， high-dose Shaoyaotang groups and the SASP group were significantly decreased， while the content of TGF-β1 in the serum of the rats in the low， medium， high-dose Shaoyaotang groups and the SASP group were significantly increased （P<0.05）. The expression levels of CD14， FADD， Caspase-8 mRNA and protein in each intervention group were significantly decreased （P<0.05）， especially in the high-dose Shaoyaotang group and the SASP group.ConclusionShaoyaotang has a certain intervention effect on UC rats with large intestine damp-heat syndrome， and its mechanism may be related to the inhibition of CD14， FADD and Caspase-8 genes and proteins expression.
Keywords：Shaoyaotang;ulcerative colitis;leukocyte differentiation antigen 14 （CD14）;Fas-related death domain protein （FADD）;cysteinyl aspartate specific protease-8 （Caspase-8）
Abstract：The classical prescription Kaixinsan，which is recorded in an ancient medical book named Beiji Qianjin Yaofang，is one of the famous prescriptions used by ancient physicians to treat amnesia. Research on classical prescriptions has attracted more and more attention from scientific research institutions and related enterprises. Based on ancient books，textual research on origins and development of prescriptions，combing the evolution of prescriptions，preparations，oral ways，taboos and others are the important contents of the study on classical prescriptions. The research results show that the creation of Kaixinsan in Beiji Qianjin Yaofang can be traced back to Kaixinsan recorded in Jiyanfang and Dingzhiwan recorded in Gujinluyanfang. Later generations of physicians created many associated prescriptions in the process of applying Kaixinsan，and the efficacy of these prescriptions was constantly expanded with the development of the times. In the Tang and Song dynasties，Kaixinsan and its associated prescriptions were mainly used to treat amnesia，sorrow，fear，and other diseases. In the Jin and Yuan dynasties，these prescriptions were also used to treat convulsions and yawning. In the Ming dynasty， they were mainly for the treatment of hyperopia， myopia， sprematorrhea，and constipation. In the Qing dynasty，these herbs could be used to treat auricular deafness， aging and sweating. The dosage of Ginseng Radix et Rhizoma and Poria should be increased in the treatment of farsightedness，spermatorrhea and blurred urine，and in the treatment of nearsightedness，the dosage of Polygalae Radix and Haliotidis Concha should be increased. The main pathogenesis of the disease that Kaixinsan and its associated prescriptions treated could be summarized as the deficiency of heart and spleen，imbalance between heart-Yang and kidney-Yin，and the internal resistance of phlegm stagnation. By summarizing the contents of the preparation of tradition Chinese medicine products for Kaixinsan and its associated prescriptions，it is suggested that the dosage form of Kaixinsan can be pills，with the specification size confroming to the most record of ancient generations of physicians，as big as Firmiana platanifolia's fruit.The volume of a single pill is about 0.25 mL and the weight is about 0.3 g. The initial dosage is fifteen pills，which can be modified according to the severity of the illness，with no more than forty pills for each time，three times a day. Also，some excitant food like the sour food，sweet food and mutton should be avoided during the medication. The above research results can provide literature basis for the development of compound tradition Chinese Medicine preparation of Kaixinsan.
Keywords：famous classical formulas;Kaixinsan;associated prescriptions;compound preparation;textual research
Abstract：ObjectiveTo investigate the neuroprotective effects of Danggui Shaoyaosan （DSS） on APPswe/PS1ΔE9 transgenic （APP/PS1） mice and its mechanism related to circular RNA （circRNA）.MethodTotally twenty 6-month-old APP/PS1 mice were divided into model group and DSS group， and 10 C57BL/6 wild-type mice were set as the normal control group. The normal group and model group received the same volume of normal saline， and DSS group received drug by gavage administration， all for 8 weeks. The differentially expressed circRNA of APP/PS1 mice before and after DSS intervention was analyzed by circRNA sequencing to construct circRNA-miRNA mRNA interaction network. The results of cricRNA sequencing were then verified by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of phosphoinositide 3-kinase （PI3K）， p-PI3K， protein kinase B1 （Akt1）， p-Akt1， B lymphocytoma-2 （Bcl-2）， and Bcl-2-Associated X protein （Bax） in the hippocampus were detected by immunoblotting （Western blot）. The protein expression of Caspase-3 in the hippocampus was detected by immunohistochemistry and the level of apoptosis in the hippocampus was detected by the TUNEL method.ResultCompared with the model group， there were 90 differentially expressed circRNA after intervention with DSS， of which 46 were up-regulated and 44 down-regulated. Compared with the normal group， the expression levels of circRNA1398 and circRNA1399 in the model group decreased， and the expression levels of miR-103-3p， miR-153-3p， miR-143-3p， and miR-143-5p increased. Compared with the model group， the expression levels of circRNA1398 and circRNA1399 in the DSS group were up-regulated， while the expression levels of miR-103-3p， miR-153-3p， miR-143-3p， and miR-143-5p were down-regulated. Compared with the normal group， the expression of p-PI3K， Akt1， p-Akt1， and Bcl-2 in the model group decreased （P<0.05， P<0.01）， and the expression of Bax and Caspase in the model group increased （P<0.01）. Compared with the model group， the expression of p-PI3K， Akt1， p-Akt1， and Bcl-2 in the hippocampus of the DSS group increased （P<0.01）， and the protein expression of Bax and Caspase decreased （P<0.01）. Compared with the normal group， the apoptosis level in the hippocampus of the model group increased， with an apoptosis rate of （43.76±2.92）%. Compared with the model group， the apoptosis rate of DSS group was （24.64±3.39）%.ConclusionDSS can activate PI3K/Akt pathway and inhibit apoptosis in hippocampal neurons of APP / PS1 mice， and play a neuroprotective role. The specific mechanism may be related to the regulation of circRNA1398 and circRNA1399 expression and the corresponding miRNA expression.
Abstract：ObjectiveTo explore the possible mechanism of Kaixinsan in improving cognitive impairment in Alzheimer's disease （AD） model rats based on the epichlorohydrin associated protein-1 （Keap-1）/nuclear factor E2 related factor （Nrf2）/manganese superoxide dismutase （MnSOD） signaling pathway.MethodThe AD model was established by injecting Amyloid β1-42 （Aβ1-42， 5 μL） into the lateral ventricle. After modeling， the experimental rats were randomly divided into model group， donepezil group， and Kaixinsan low dose， medium dose and high dose groups. Another normal control group was also established. The donepezil group received donepezil tablets （1.8 g·kg-1·d-1）， Kaixinsan low dose， medium dose and high dose groups received corresponding doses of Kaixinsan （10， 20， 40 g·kg-1·d-1， respectively）， and the normal control group and model group were given with equal volume of pure water. Morris water maze was used to test the learning and memory ability of rats. The pathological morphology of hippocampal CA3 area was observed by Nissl staining. The expression levels of myeloperoxidase （MPO）， inducible nitric oxide synthase （iNOS） and superoxide dismutase （SOD） in serum were detected by colorimetry， and the protein expression levels of Keap-1， Nrf2 and MnSOD in hippocampus were detected by immunohistochemistry （IHC） and Western bolt.ResultCompared with the normal control group， the escape latency， total swimming distance and first arrival time of the plateau in the model group increased （P<0.01）， while the times of crossing the plateau and the time in target quadrant decreased （P<0.01）. Compared with the model group， the rats in donepezil group and Kaixinsan groups showed less latency， lower total swimming distance and first arrival time on the platform （P<0.05， P<0.01）， while the times of crossing the platform and time in target quadrant increased （P<0.05， P<0.01）. Compared with the normal control group， the expression levels of MPO and iNOS in serum of the model group increased （P<0.01）， while the expression levels of SOD decreased （P<0.01）. Compared with model group， the expression of MPO and iNOS in serum of donepezil group and Kaixinsan groups decreased （P<0.05， P<0.01）， while the expression of SOD increased （P<0.05， P<0.01）. In the normal control group， the neurons in the hippocampal CA3 of the rats were arranged neatly， without obvious Nissl body shrinkage. The neurons in the CA3 of the hippocampus of the model group were not arranged neatly， with obvious neuron loss and pyknosis of Nissl body. The neurons in the CA3 of the hippocampus of the rats in the donepezil group and Kaixinsan groups were arranged neatly， with increased number of neurons and decreased Nissl body shrinkage. Compared with the normal control group， the integrated optical density （IA） and protein level of Keap-1 in the hippocampus of the model group decreased（P<0.01）， while the IA and protein level of Nrf2 and MnSOD increased （P<0.01）. Compared with model group， IA and protein levels of Keap-1 and MnSOD in hippocampus of rats in donepezil group and Kaixinsan groups increased （P<0.05， P<0.01）， while IA and protein levels of Nrf2 decreased （P<0.05， P<0.01）.ConclusionKaixinsan could alleviate memory impairment in AD rats， and its mechanism may be related to its regulation of Keap-1/Nrf2/MnSOD signaling pathway.
Abstract：ObjectiveTo study the effect of Bushen Huatan prescription on helper T cell 17 （Th17）/T regulatory cells （Treg） balance of immune T cell subsets in the prevention and treatment of postmenopausal osteoporosis.MethodSixty 6-month-old female SD rats were randomly divided into sham operation group， model group， estradiol valerate group （0.184 mg·kg-1） and Bushen Huatan prescription low， medium and high groups （4.7， 9.4， 18.8 g·kg-1） according to the random number table. All the groups except the sham operation group received ovariectomy to make postmenopausal osteoporosis model. Intragastric administration was started 1 week after operation， and the rats in model group and sham operation group received equal volume of normal saline， once a day for 12 weeks. Microcomputed tomography （Micro CT） was then used to detect bone mass and microstructure of rats， the contents of Forkhead box protein （Foxp3） and retinoic acid related nuclear orphan receptor （RORγt） in serum were detected by enzyme-linked immunosorbent assay （ELISA）， the mRNA expression levels of Foxp3 and RORγt in bone tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot was used to detect the protein expression of Foxp3 and RORγt in bone tissues， the number of Th17 and Treg cells in each group was analyzed and compared by flow cytometry.ResultCompared with the sham operation group， the bone mass and trabeculae of the model group decreased （P<0.01）， the bone microstructure was destroyed， the concentration of Foxp3 in serum decreased， the concentration of RORγt increased （P<0.01）， the mRNA and protein expression levels of Foxp3 in bone tissues decreased， RORγt increased， the number of Treg cells in bone tissues decreased， number of Th17 cells increased （P<0.01）， and Th17/Treg ratio increased （P<0.01） in model group. Compared with the model group， the bone mass in each treatment group increased （P<0.05， P<0.01）， Foxp3 concentration in serum increased， RORγt concentration decreased （P<0.01）， the mRNA and protein expression levels of Foxp3 in bone tissues increased significantly （P<0.05， P<0.01）， but no statistical difference was shown in mRNA expression between low dose group and the model group. In addition， the mRNA and protein expression of RORγt decreased （P<0.05， P<0.01）， number of Treg cells increased， number of Th17 cells decreased （P<0.05， P<0.01）， and Th17/Treg ratio decreased in treatment groups （P<0.01）.ConclusionBushen Huatan prescription can increase bone mass， improve bone microstructure， increase the number of Treg cells and decrease the number of Th17 cells in ovariectomized rats. It is concluded that Bushen Huatan prescription may play a role in preventing and treating postmenopausal osteoporosis by regulating Th17/Treg balance.
Abstract：ObjectiveTo investigate the therapeutic effect and mechanism of modified Wenjingtang on endometriosis （EM） rats with kidney deficiency and blood stasis.MethodThe 10 from 105 SPF female healthy SD rats were randomly selected as the blank group. The rest constructed the rat model of kidney deficiency and blood stasis by compound factorial method. After the model was successfully established， 10 rats were randomly selected as the sham operation group， with only laparotomy and no intima suture， and the remaining rats were established with EM kidney deficiency and blood stasis type by autologous intimal transplantation. Fifty rats which were randomly selected from 56 successful rats were treated with the modified Wenjingtang （5，10，20 g·kg-1） and danazol group（63 mg·kg-1）， 1 time daily ， for 4 weeks. The endometrial tissues of each group were stained with hematoxylin eosin （HE） to observe the histopathology. The levels of inflammatory factors interleukin-10 （IL-10） and interleukin-17 （IL-17） in serum supernatant were detected by enzyme linked immunosorbent assay （ELISA）. Measuring the length（D1），width （D2） and height （D3） of the heterotopic foci in each group before and after treatment. Then calculating the volume of them. The expression of tyrosine kinase 2（JAK2），transcription factor 3 （STAT3），phosphorylation transcription factor 3 （p-STAT3）， vascular endothelial growth factor （VEGF）， tumor necrosis factor-α （TNF-α） and thrombospondin-1 （TSP-1） were detected by immunohistochemistry （IHC）. The expression of VEGF，TNF-α and TSP-1 was detected by Western blot.ResultMicroscopic pathological observation showed that the endometrial glandular cells of the blank group were arranged in order， and the glandular and stromal cells grew well， compared with the blank group， the endometrial structure of the model group was complete， showing a cavity like or annular closed structure， with cyst formation， and the epithelium was cubic or columnar epithelium， most of the epithelial cells had secretion， the stroma was dense， and the matrix showed a little fibrosis There were a few glands and inflammatory cell infiltration. Compared with the blank group， the content of IL-10 in serum of model group was significantly decreased （P<0.01）， and the content of IL-17 was significantly increased （P<0.01）， the protein expression of JAK2， STAT3，p-STAT3， VEGF， TNF-α in endometrial tissue of model group was significantly increased （P<0.05）， and the expression of TSP-1 protein was significantly decreased （P<0.05）. Compared with the model group， the serum IL-10 content of rats in modified Wenjingtang treatment group increased significantly （P<0.01）， the IL-17 content decreased significantly （P<0.01）， and the volume of ectopic foci decreased significantly （P<0.01）. While the level of JAK2，STAT3，p-STAT3，TNF-α，VEGF protein in intimal tissue of modified Wenjingtang high and middle dose group decreased significantly （P<0.05） and the level of TSP-1 protein increased significantly （P<0.05）.ConclusionModified Wenjingtang can inhibit the invasion of ectopic foci in EM rats with kidney deficiency and blood stasis， the mechanism may be related to the intervention of immune barrier and block angiogenesis function mediated by JAK2/STAT3 signaling pathway activation.
Abstract：ObjectiveTo investigate the effect and mechanism of PAE2， a polypeptide of Periplaneta americana， in reversing multidrug resistance （MDR） for liver cancer in vivo.MethodBalb/c-nude mice were inoculated with HepG2 and HepG2/ADM cells under the armpits to establish animal models of liver cancer sensitive strains and animal models of MDR respectively. After successful modeling， the nude mice were randomly divided into normal group， HepG2 model group， HepG2/ADM model group， sorafenib group （positive drug control group， ig 30 mg·kg-1）， HepG2/ADM+PAE2 （iv） low， medium and high dose groups （50， 100， 200 mg·kg-1）， HepG2/ADM+PAE2 （ig） low， medium， and high dose groups （50， 100， 200 mg·kg-1）， skim cream group （ig 200 mg·kg-1）， and CⅡ-3 group （ig 200 mg·kg-1）， all of which received corresponding drug treatment. The body weight and tumor volume of nude mice were measured and recorded every 2 days. The next day after the last administration， tumor tissues of nude mice were taken to record the tumor weight. The effect of P. americana polypeptide PAE2 on permeability-glycoprotein（P-gp）， lung resistance protein（LRP） ， breast cancer resistance protein（BCRP）， protein kinase C（PKC）， glutathione S-transferase-π（GST-π）， topo-isomerase typeⅡ（ToPoⅡ）， multidurg resistance gene 1（MDR1）and Multidrug resistance-associated proteins（MRP1） of the protein level and gene level expression in tumor tissues were determined by immunohistochemistry （IHC） and real-time quantitative polymerase chain reaction （Real-time PCR）. In addition， both oral and intravenous administration groups were set up at the same time for preliminary study on the basic pharmacokinetic characteristics of P. americana polypeptide PAE2.ResultAfter the successful modeling， the body weight of the nude mice was significantly lower than that in the normal mice（P<0.05）. After treatment with corresponding drugs， the body weight increased to a certain extent， but it was still not as good as the normal nude mice. In iv administration， the medium-dose P. americana polypeptide PAE2 showed the best anti-tumor effect as compared with the model group （P<0.05）， while in oral administration， the anti-effect increased with the increase of the dose， so the high-dose group showed the best effect （P<0.05）. Preliminary crude extract CII-3 had no obvious anti-tumor effect， and skim cream showed a certain anti-tumor effect （P<0.05）. P. americana polypeptide PAE2 had certain effects on MDR related proteins and enzymes in vivo， mainly by inhibiting the expression of LRP and BCRP in tumor tissues and affecting the expression of these related proteins and genes to different degrees to inhibit intracellular drugs outflow， thereby promoting tumor apoptosis， and the effect was superior to that of the P. americana crude extract CⅡ-3 and skim cream.ConclusionP. americana polypeptide PAE2 may reduce the drug efflux， promote intracellular drug accumulation and apoptosis by affecting the expression of related proteins and enzymes that mediate multidrug resistance， thereby exerting a reverse effect on HepG2/ADM cells Balb/c MDR in nude mice.
Keywords：Periplaneta americana polypeptide PAE2;anti-tumor;multi-drug resistance
Abstract：ObjectiveTo study the effect of Fushengong prescreption on the regulation-antagonism effect of angiotensin converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ 1 receptor （ACE-AngⅡ-AT1R） axis and angiotensin converting enzyme 2-angiotensin （1-7）-Mas receptor［ACE2-Ang（1-7）-MASR］ axis of rats with chronic renal failure（CRF）， and to explore its mechanism of delaying the development of CRF.MethodThe 65 male SD rats were randomly divided into normal group （n=10） and modeling group （n=55）. The normal group was routinely reared， while the modeling group were administered by gavage with 0.25 g·kg-1d-1 adenine suspension for 28 days. After the model was successfully established， the survival model rats were randomly divided into model group， benazepril group（0.01 g·kg-1·d-1）and low，medium and high dose of Fushengong prescreption groups （4，8，16 g·kg-1·d-1）. The normal group and model group were administered the same volume of normal saline by gavage， lasted for 28 days. After the experiment， systolic blood pressure （SBP） and diastolic blood pressure （DBP） of caudal artery were measured， and 24-hour urine was collected to determine 24-hour urine protein （24 h U-pro）. The content of serum creatinine（SCr） and blood urea nitrogen （BUN） in the serum were measured， the histological morphology was observed by hematoxylin eosin（HE）staining， and the degree of renal interstitial fibrosis was observed by Masson staining. Enzyme linked immunosorbent assay （ELISA） was used to determine the contents of AngⅡ， Ang （1-7） and Cystatin C （CysC） in serum and renal homogenate. The protein level of ACE， ACE2， AT1R and MASR were detected by Western blot. The expression of ACE and ACE2 protein in renal tissues were detected by immunohistochemistry.ResultCompared with normal group， the expression levels of SCr， BUN and CysC in model group were significantly increased（P<0.05）， the content of AngⅡ in serum and kidney tissues were significantly increased， the content of Ang （1-7） were significantly decreased（P<0.05）， the expression of ACE and AT1R protein in renal tissues were significantly increased（P<0.05）， and the expression of ACE2 and MASR protein were significantly decreased（P<0.05）. Compared with model group and benazepril group， after the intervention with Fushengong prescreption， the serum SCr，BUN and CysC decreased（P<0.05），the content of AngⅡ in serum and kidney tissues decreased significantly，Ang（1-7） increased significantly（P<0.05）， the expression of ACE and AT1R protein in renal tissues decreased significantly（P<0.05）， ACE2 and MASR protein increased significantly（P<0.05）. The high-dose Fushengong prescreption has the best effect. The high， medium and low-dose effects of Fushengong prescreption were dose-dependent.ConclusionFushengong prescreption improved renal function and pathological change of kidney in adenine-induced rats with chronic renal failure. The mechanism may be related to the inhibition of ACE-AngⅡ-AT1R axis and promotion of ACE2-Ang（1-7）-MASR axis ，which leads to the delaying of the progression of chronic renal failure.
Abstract：ObjectiveTo investigate the antitumor effect and the mechanism of Dunhuang Pingweiwan and its decomposed recipes based on phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway in SCG-7901 gastric cancer-mice.MethodThe subcutaneous tumor bearing model of SCG-7901 gastric cancer in mice was established， and the the mice were randomized into model group， Dunhuang Pingweiwan group （14.04 g·kg-1·d-1）， Huoxue Jiedu group （6.50 g·kg-1·d-1）， Wenzhong Sanhan group （3.64 g·kg-1·d-1） and cisplatin group （2 mg·kg-1·d-1）， with 8 mice in each group. From the 8th day of inoculation， the mice were administered for 10 consecutive days. The mice were weighed and the general conditions were observed every other day. On the next day of the last administration， the mice were sacrificed， and the tumor was removed and weighed to calculate the anti-tumor rate. The histopathological changes were observed by hematoxylin-eosin （HE） staining， and the mRNA and protein expressions of PI3K， Akt， and mTOR in tumor tissues were detected by real-time polymerase chain reaction（Real-time PCR） and immunohistochemistry （IHC）， respectively.ResultFrom the 10th day of inoculation， the mice in cisplatin group were generally in poor condition and their body mass decreased. The mice in model group， Dunhuang Pingweiwan group， Huoxue Jiedu group and Wenzhong Sanhan group were generally fair， and their body mass increased without significant difference among groups. The tumor inhibition rates of Dunhuang Pingweiwan， Huoxue Jiedu， Wenzhong Sanhan and cisplatin groups were 30.74%， 24.80%， 4.19% and 63.84%， respectively. Except for Wenzhong Sanhan group， tumor weight of the other treatment groups was significantly lower than that of the model group （P<0.01）， and there was no significant difference between the Dunhuang Pingweiwan and Huoxue Jiedu group. Dunhuang Pingweiwan and Huoxue Jiedu group could significantly reduce tumor cell density and cause tumor cell necrosis. Compared with the model group， the expressions of PI3K， Akt， and mTOR mRNA and protein in the Dunhuang Pingweiwan， Huoxue Jiedu and cisplatin groups significantly decreased （P<0.05， P<0.01）， and there was no significant difference between the Dunhuang Pingweiwan group and Huoxue Jiedu group.ConclusionDunhuang Pingweiwan and its decomposed recipes （Huoxue Jiedu） have a certain anti-tumor effect on the SCG-7901 gastric cancer-mice， and the mechanism may be related to the down-regulation of key molecules in the PI3K/Akt/mTOR signaling pathway.
Keywords：Dunhuang Pingweiwan;gastric cancer;phosphatidylinositol 3-kinase （PI3K）;protein kinase B （Akt）;mammalian target of rapamycin （mTOR）
Abstract：ObjectiveTo investigate whether the adverse reactions of Xuebijing injection (XBJJ) are mainly pseudoallergic reactions and explore the influencing factors of its pseudoallergic reactions.MethodMouse model of pseudoallergic reaction was used to study the anaphylactoid reaction of XBJJ which at 0.5, 1 and 2 times of the highest clinical concentration. Next, we compared the differences in pseudoallergic reactions caused by XBJJ for different storage times after preparation. Specifically, XBJJ was prepared into different concentrations, stored for 10 minutes, 2.5 hours, 6 hours and 24 hours, and then injected into the tail vein of mice. Finally, three different injection speeds of 3 seconds, 45 seconds and 90 seconds were selected for XBJJ injection, and then the differences in the paeudoallergic reactions induced by XBJJ in mice under different injection speeds were compared.ResultXBJJ induces pseudoallergic reactions in mice when the drug concentration is higher than the clinically recommended concentration. Compared with storage for 10 minutes after preparation, the degree of pseudoallergic reaction in mice induced by the same concentration of XBJJ increased with the extension of storage time. In addition, when XBJJ was injected in 3 s (the injection rate was 0.083 mL·s-1), it produced the strongest pseudoallergic reaction.ConclusionThe adverse reactions induced by XBJJ are mainly pseudoallergic reactions. Excessive storage time after preparation and fast injection speed of XBJJ will lead to aggravation of pseudoallergic reactions in mice. When XBJJ is used clinically, it should strictly follow the usage, dosage, concentration, and drip rate recommended in the drug instruction manual. Rational drug use is of positive significance for improving the safety of XBJJ.
Keywords：Xuebijing injection;adverse reaction;pseudoallergic reaction;rational administration of drug
Abstract：ObjectiveTo evaluate the effect of Mashao Pingchuan decoction on traditional Chinese medicine （TCM） symptoms， quality of life， peripheral blood eosinophils （Eos） and serum inflammatory factors interleukin-6 （IL-6） and interleukin-8 （IL-8） in patients with cold asthma syndrome of bronchial asthma.MethodA total of 67 patients with cold asthma who attended the Respiratory Clinic of Anhui Provincial Hospital of TCM from January 2018 to December 2019 were selected and randomly divided into a control group and an observation group. The control group was given basic treatments such as budesonide formoterol powder inhalation， and the observation group was given Mashao Pingchuan decoction on the basis of the control group. Both groups intervened for 7 consecutive days. Observe and record the general condition， TCM symptom score， asthma control questionnaire （ACQ）-7 score， Marks-asthma quality of life questionnaire （Marks-AQLQ） score of the two groups of asthma patients， the peripheral blood Eos count was measured by hematology analyzer， and the serum IL-6 and IL-8 levels of the subjects were measured by enzyme-linked immunosorbent assay （ELISA）.ResultThe total effective rate of TCM symptoms in the two groups was 100%（30/30）， and the effect in the observation group was more obvious （Z=-2.169，P<0.05）. After treatment， the scores of TCM symptoms in the two groups were significantly lower than those before treatment （P<0.01）. The scores of phlegm in the throat， expectoration， cough， and chills in the observation group were lower than those in the control group （P<0.05）. After treatment， the ACQ-7 scores and Marks-AQLQ scores of the two groups were significantly lower than before treatment （P<0.01）. There was no statistically significant difference between the observation group and the ACQ-7 scores and Marks-AQLQ scores. After treatment， the peripheral blood Eos counts and serum IL-6 and IL-8 levels in the two groups were significantly lower than before treatment （P<0.01）. Peripheral blood Eos count and serum IL-6 and IL-8 contents in observation group were lower than those in control group （P<0.05）.ConclusionMashao Pingchuan decoction combined with budesonide formoterol powder inhalation can effectively improve the clinical effectiveness of asthma （cold asthma）， improve the symptoms of asthma in TCM， ACQ-7 score， Marks-AQLQ score， peripheral blood Eos count， serum inflammatory factor content.
Keywords：Mashao Pingchuan decoction;bronchial asthma;cold asthma;curative effect evaluation;quality of life
Abstract：ObjectiveTo explore the efficacy and mechanism of modified Da Chengqitang in treating hyperlipidemic acute pancreatitis （HLAP） with damp heat accumulation syndrome.MethodA total of 110 patients with HLAP with damp heat accumulation syndrome treated at our hospital were randomly divided into control group and observation group， with 55 cases in each group， both groups were treated with low molecular weight heparin calcium， insulin and alprostadil injection. Control group was given Huazhironggan granules in addition to the basic therapy， while observation group was given modified Da Chengqitang in addition to the basic therapy. After 7 days， the clinical efficacy， traditional Chinese medicine (TCM） syndrome score， gastrointestinal function recovery， acute pancreatitis bedside index （BISAP）， acute physiology and chronic health status Ⅱ （APACHE Ⅱ）， inflammatory factors， such as tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and C-reactive protein （CRP）， oxidative stress， such as malondialdehyde （MDA）， oxidized glutathione （GSSG）， total antioxidant capacity （T-AOC）， total cholesterol （TC）， triglyceride （TG）， high and low density lipoprotein （HDL-C， LDL-C） blood lipid indicators and safety were evaluated.ResultThe clinical efficacy of observation group was significantly better than that of control group （Z=3.353， P<0.05）， and the total effective rate of observation group was 94.55%， which was higher than 74.55% of control group （χ2=8.419， P<0.01）. After treatment， the scores of abdominal pain， stool obstruction， chest tightness and fever in observation group were significantly lower than those of control group （P<0.05）. The gastric tube indwelling exhaust time， defecation time and recovery time of bowel sounds in observation group were significantly lower than those of control group （P<0.05）. The scores of BISAP and APACHE Ⅱ in two groups were significantly decreased， and the BISAP and APACHE Ⅱ scores of observation group were lower than control group （P<0.05）. After treatment， the serum levels of TNF-α， IL-6 and CRP in observation group were significantly lower than those in control group. The levels of serum MDA， GSSG in two groups were significantly decreased， whereas the T-AOC level was significantly increased； and the level of serum MDA， GSSG observation group was lower than control group， while the T-AOC level was higher than control group （P<0.05）. After treatment， the levels of TC， TG and LDL-C in two groups were decreased， while the level of HDL-C was increased， the levels of TC， TG and LDL-C in observation group were lower than those in control group， and the HDL-C was higher than that control group （P<0.05）.Conclusionmodified Da Chengqitang has a definite clinical efficady in treating HLAP with damp heat accumulation syndrome， and can alleviate TCM syndrome and patient symptoms， reduce inflammatory factors， inhibit oxidative stress of the body. It has a good safety， and is worthy of clinical application.
Abstract：ObjectiveTo explore the regulatory effect of modified Liu Junzitang on the immune function， nutritional status and intestinal microecology in advanced gastric cancer patients with syndrome of deficiency of Qi and blood.MethodThe 86 advanced gastric cancer patients with syndrome of deficiency of Qi and blood were randomly divided into control group and observation group according to their admission numbers， with 43 cases in each group. The control group was given Yiqi Yangxue oral liquid on the basis of basic treatment while the observation group was given modified Liu Junzitang. After 4 weeks， compare the clinical efficacy of two groups of patients， traditional Chinese medicine （TCM） syndrome score， gastrointestinal function recovery， adverse reaction and quality of life， immune function， T cell subsets CD3+， CD4+， CD8+， C3 and C4 levels， immunoglobulin A （IgA）， immunoglobulin G （IgG）， immunoglobulin M （IgM）， nutritional status： albumin （propagated）， prealbumin （PA）， serum total protein （TP） and hemoglobin （Hb） content changes， the intestinal micro ecology： Bifidobacterium， Lactobacillus， Enterococcus aureus， Escherichia coli content changes.ResultThe total effective rate of the observation group was 95.35% （41/43）， which was significantly higher than 79.07% （34/43） of the control group （χ2=5.108，P<0.05）， after treatment， the TCM syndromes such as dizziness， pale complexion， palpitation， shortness of breath and fatigue in the observation group were significantly lower than those in the control group （P<0.05）， the bowel sound recovery， exhaust and defecation time of the observation group were significantly lower than those of the control group （P<0.05）， the quality of life scores in the observation group， such as the nature-to-human correspondence， form and spirit integration， specific modules， functional areas， and overall health score， were significantly higher than those in control group （P<0.05）， the CD3+， CD4+， CD4+/CD8+， C3， C4， IgA， immune function indexes such as IgG and IgM were significantly higher than those of the control group， and the CD8+ level was lower than which of control group （P<0.05）， the nutritional status levels such as Alb， PA， TP and Hb in the observation group were significantly higher than those of the control group （P<0.05）， Bifidobacterium， Lactobacillus， and E. faecalis in the observation group were higher than those in the control group， and E. coli was lower than the control group （P<0.05）， the adverse reaction rate of the observation group was 11.63% （5/43） and the control group was 16.28% （7/43） ， and there was no statistical difference between two groups.ConclusionModified Liu Junzitang has a good clinical effect on advanced gastric cancer patients with syndrome of deficiency of Qi and blood. It can improve TCM syndromes and gastrointestinal function， improve quality of life， and its mechanism is related to improving immune function， enhancing nutritional status， and improving intestinal microecology， and it has good safety.
Keywords：modified Liu Junzitang;advanced gastric cancer;syndrome of deficiency of Qi and blood;immune function;nutritional status;intestinal microecology
Abstract：ObjectiveTo discuss the clinical efficacy of Qingfei Xiegantang on chronic inflammation and endothelial function of people of Taiyin constitution with metabolic syndrome （MS）.MethodPatients （162 cases） were divided into control group （80 cases） and observation group （82 cases）. Both groups got lifestyle intervention and treatment with lipid regulation， blood pressure reduction and hypoglycemia according to MS. Patients in observation group got Qingfei Xiegantang， 1 dose/day. Patients in control group got placebo granules of Qingfei Xiegantang. The treatment lasted for 4 months. Before and after treatment， weight， height， waist （WC）， hip， body mass index （BMI） and waist hip ratio （WHR） were calculated. Levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （2 hPG）， glycosylated hemoglobin （HbA1c） and fasting insulin （FINS） were measured. Insulin resistance index （HOMA-IR）， insulin sensitivity index （ISI） and islet beta cell function index （HOMA-β）， systolic blood pressure （SBD）， diastolic blood pressure （DBP）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， leptin （LP）， adiponectin （ADP）， nitric oxide （NO）， endothelin-1 （ET-1）， endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were detected and recorded. Then the safety was evaluated.ResultLevels of body mass， BMI， WHR， TG， TC， LDL-C， FBG， 2 hPG， HbA1c， HOMA-IR， SBD， DBP， TNF-α， IL-6， LP， ET-1 and iNOS were all lower than those in control group. Levels of HDL-C， InISI， HOMA-β， ADP， NO and eNOS were higher than those in control group （P<0.01）. And score of syndrome differentiation of Taiyin people was lower than that in control group （P<0.01）. The compliance rate of BMI in observation group was 70.27% （52/74）， which was higher than 53.42% （39/73） in control group （χ2=4.421， P<0.05）. The compliance rate of blood pressure was 95.95% （71/74）， was higher than 84.93% （62/73） in control group （χ2=5.171， P<0.05）. The compliance rate of blood fat was 87.84% （65/74）， which was higher than 72.60% （53/73） （χ2=5.386， P<0.05）.ConclusionQingfei Xiegantang can regulate the obesity， blood pressure， blood glucose and blood lipid components of MS， relieve clinical symptoms， improve IR， insulin sensitivity and islet β cell function， reduce inflammatory reaction， and increase vascular endothelial function of people of taiyin constitution with metabolic Syndrome.
Keywords：metabolic syndrome;people of Taiyin constitution;Qingfei Xiegantang;insulin resistance;inflammatory response;vascular endothelial function
Abstract：ObjectiveTo observe the effect of Dingkundan in adjuvant treatment of clinical symptoms， quality of life， immune function and prognosis of patients with radiotherapy and chemotherapy after endometrial carcinoma （EC） operation.MethodPatients were divided into control group （82 cases） and observation group （86 cases） according to random number table. A total of 75 patients in control group completed the study （4 patients fell off or lose visit， and 3 patients were eliminated）， while 77 patients in observation group completed the study （5 patients fell off or lose visit， and 4 patients were deleted）. After operation， patients got brachytherapy， external pelvic irradiation and chemotherapy. Patients in control group got Bazhenwan， 1 pill/time， 2 times/day， and those in observation group got Dingkundan， 7 g/time， 2 times/day. The course of treatment lasted for 4 months， and long-time follow-up data was recorded. Before treatment， and at the second and fourth month after treatment， deficiency of Qi and blood was scored. Toxic reactions after radiotherapy and chemotherapy were recorded， and incidence rate of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level were compared. And levels of T lymphocyte subsets （CD3+， CD4+， CD8+ and CD4+/CD8+） were detected， European collaborative quality of life Cancer Core Scale （EORTC QLQ-C30） was evaluated， and expressions of pce125 （CA125）， epididymis protein 4 （HE4）， Dickkopf-related protein-1 （DKK1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9） and transforming growth factor-β1 （TGF-β1） were tested before and after treatment. The follow-up was made for every three months， and the progression （recurrence/metastasis） of patients was recorded.ResultScores of deficiency of Qi and blood in observation group were lower than those in control group at the second and fourth week after treatment （P<0.01）. Incidence rates of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level and incidence rates of bone marrow suppression， gastrointestinal toxicity， neurotoxicity were lower than those in control group （P<0.05）. Five functional dimensions and overall quality of life score based on EORTC and QLQ-C30 in observation group were higher than those in control group （P<0.01）， and scores of three symptom dimensions were lower than those in control group （P<0.01）. Levels of CD3+， CD4+ and CD4+/CD8+ were higher than those in the control group （P<0.01）， and CD8+ was lower than those in the control group （P<0.01）. Levels of CA125， HE4， DKK1， VEGF， MMP-9 and TGF-β1 were lower than those in the control group （P<0.01）. The disease progression rate in observation group was 18.18% （14/77）， which was lower than 33.33% （25/75） in control group （χ2=4.572， P<0.05）.ConclusionIn adjuvant treatment of patients with radiotherapy and chemotherapy after EC operation， Dingkundan can reduce the symptoms of Qi and blood deficiency syndrome and side effects caused by radiotherapy and chemotherapy， improve the quality of life and immune function， inhibit the expression of tumor markers and tumor growth factor， delay the progression of tumor and improve the prognosis.
Keywords：endometrial cancer;Qi and blood deficiency syndrome;Dingkundan;quality of life;immune function;tumor markers;disease progression
Abstract：ObjectiveTo investigate the chemical constituents and antioxidant activities of Violae Herba from the Violaceae.MethodThe 5 kg of Violae Herba was refluxing extracted with 3 times the amount of 95% ethanol for three times， then the extracting solution was combined， filtrated， concentrated under vacuum to get the total extract. Seven corresponding fractions were eluted with petroleum ether， dichloromethane， dichloromethane-methanol （50∶1， 10∶1， 5∶1， 2∶1） and methanol by silica gel column chromatography （60-100 mesh） on the total extract. Each fraction was isolated and purified by normal phase silica gel column chromatography， octadecylsilane chemically bonded silica （ODS） column chromatography， Sephadex LH-20 column chromatography and preparative high performance liquid chromatography （HPLC）， respectively. The structures of the obtained compounds were identified by spectroscopic methods of nuclear magnetic resonance （NMR）， mass spectroscopy （MS） and infrared spectroscopy （IR）. Meanwhile， some of these compounds isolated from Violae Herba were carried on the 1，1-diphenyl-2-picrylhydrazyl （DPPH） free radical scavenging experiment.ResultFourteen compounds were isolated from the 95% ethanol extract of Violae Herba， including N-acetyl-1-ethyl ester glutamic acid （1）， N-acetyl glutamic acid-1-ethyl-5-methyl ester （2）， aurantiamide （3）， rel-（2α，3β）-7-O-methylcedrusin （4）， oleanolic acid （5）， α-tocopherol-quinone （6）， tectochrysin （7）， isoscopoletin （8）， esculetin （9）， 24-ethylcholesta-4，24（28）Z-dien-3-one （10）， stigmasta-4，25-dien-3-one （11）， β-sitostenone （12）， β-sitosterol （13）， （24R）-3β-hydroxy-ethylcholest-5-en-7-one （14）.ConclusionCompound 2 is a new natural product， compounds 1， 4， 6， 7， 10-12 are isolated from the genus Viola for the first time. Compound 9 has significant antioxidant activity， while compounds 2， 6 and 8 have certain DPPH free radical scavenging activity.
Abstract：ObjectiveTo analyze the sequence characteristics，chromosomal location，gene structure，conserved motifs，phylogenetic evolution and differential gene expressions of the Cannabis sativa YABBY transcription factor family，in order to provide a molecular basis for in-depth study of YABBY gene function and theoretical support for the selection and breeding of superior hemp varieties.MethodThe bio-informatics method was used to identify and analyze the CsYABBY gene family of the original hemp seed plant. PlantTFDB，ExPASy，MEME，CELLO，PLANTCARE and other online websites and TBtools，MEGA，DNAMAN and other software were used for prediction，visualization and analysis.ResultC. sativa contains 6 YABBY gene members distributed on 5 chromosomes，in which 5 members are localized in the nucleus and 1 in extracellular， they consist of 185-235 amino acids， and the isoelectric point is between 5.05 and 9.34， the molecular weight is between 20 582.45-26 282.7 Da. All of CsYABBY proteins contain two conserved domains， namely Zinc finger domain and YABBY domain. CsYABBY genes have multiple cis-acting elements，and their expressions differ in different tissues and cultivars.ConclusionThe expressions of CsYABBY may be affected by hormones and externally environmental factors. CsYABBY gene expressions are tissue-specific. In addition，YABBY transcription factor family may play an important role in regulating the development of C. sativa female flowers，and subfamilies YAB1 and YAB5 may be involved in the synthesis of cannabinoids.
Abstract：ObjectiveTo study on the quality regionalization of Angelica sinensis，in order to guide the rational cultivation of A. sinensis.MethodThrough visits and field surveys，a total of 857 batches of A. sinensis were collected from different counties of Dingxi，relevant geographic information such as longitude，latitude，altitude of each sampling point were obtained by using the global positioning system（GPS），the content of 8 indexes in A. sinensis was detected by UPLC， and based on national ecological environment factor data，the suitability analysis of the quality of A. sinensis was performed by using MaxEnt，ArcGIS，SPSS.ResultThe suitable areas of A. sinens were concentrated in central and southern Dingxi. In the suitable areas，the content of ferulic acid，coniferyl ferulate，senkyunolide H decreased from south to north，the content of chlorogenic acid decreased from north to south，the content of senkyunolide A，senkyunolide I decreased from east to west，the distribution regularity of butenyl phthalide was not strong，the highest-content areas were in western Min county，Qingyuan town of Qingyuan county，Shangwan Township and Huichuan town. The content of ligustilide was consistent in the suitable area，and the highest content were in the middle of Weiyuan county and the northern Tongwei county. The results showed that it had a higher index components and comprehensive quality in Min county，Zhang county，southern Weiyuan county and northern Tongwei county.ConclusionIn this study，the quality suitability areas of A. sinensis in Dingxi were graded. The chemical components and the quality suitability zoning maps were generated. The findings could provide references for the comprehensive utilization of A. sinensis，the selection and construction of high-quality A. sinensis raw material base，and the scientific guidance for the production and regional development of A. sinensis in Dingxi.
Abstract：ObjectiveTo establish the grade evaluation standard of Salviae Miltiorrhizae Radix et Rhizoma decoction pieces combining traditional character evaluation and modern intrinsic quality analysis.MethodThe appearance character parameters （thickness and weight） and contents of internal index components （tanshinones and salvianolic acid B） of 18 batches of Salviae Miltiorrhizae Radix et Rhizoma decoction pieces were determined， and the relative quality constant was calculated. The maximum value of the percentage quality constants of the tested samples was assumed to be 100%， the value ≥80% was classified as the first-class， ≥50% and <80% as the second-class， <50% as the third-class.ResultThe relative quality constants of 18 batches of Salviae Miltiorrhizae Radix et Rhizoma decoction pieces ranged from 349 to 884. According to the percentage quality constant， 18 batches of samples were successfully divided into three grades. The relative quality constant of the first-class product was ≥707， including samples ds5， ds8 and ds14， accounting for about 17% of the total number of samples. The relative quality constant of the second-class product was ≥442 and <707， accounting for about 61% of the total number of samples. the other samples were of the third-class， and their relative quality constants were all <442.ConclusionThe method of relative quality constant overcomes the one-sidedness of the single method in the grade evaluation of Salviae Miltiorrhizae Radix et Rhizoma decoction pieces， and the evaluation results can objectively， reasonably and scientifically classify the grade of the decoction pieces， which can provide reference for the establishment of the grade standard of other decoction pieces.
Keywords：Salviae Miltiorrhizae Radix et Rhizoma;quality constant;decoction pieces;grade evaluation;tanshinones;salvianolic acid B;appearance
Abstract：ObjectiveTo explore the molecular mechanism of Jiangtang Xiaozhi tablets （JTXZT） in the treatment of non-alcoholic fatty liver disease （NAFLD） by means of network pharmacology and molecular docking.MethodWith the help of traditional Chinese medicine （TCM） Systems Pharmacology Database and Analysis Platform （TCMSP）， TCMs Integrated Database （TCMID）， Encyclopedia of TCM （ETCM） and Bioinformatics Analysis Tool for Molecular Mechanism of TCM （BATMAN-TCM）， the chemical compositions of medicinal materials in JTXZT were obtained， the compound targets were predicted in SwissTargetPrediction database and STITCH database. The targets of NAFLD were searched by The Human Gene Database （GeneCards）， Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD） and DisGeNET， and intersection analysis was performed with the targets of the active ingredients to obtain the targets of JTXZT for treatment of NAFLD. Based on STRING 11.0 database， the protein-protein interaction （PPI） network of therapeutic targets was constructed， and the enrichment analysis of therapeutic targets was carried out by DAVID 6.8. Finally， the interaction characteristics of key components and core therapeutic targets of JTXZT for treatment of NAFLD were verified based on molecular docking.ResultThe key components of JTXZT for treatment of NAFLD were quercetin， luteolin， kaempferol， berberine， isorhamnetin， betulinic acid， oleanolic acid， ursolic acid. formononetin and hexitol， and the core targets of JTXZT for treatment of NAFLD were mitogen-activated protein kinase 1 （MAPK1）， Jun proto-oncogene， activator protein-1 （AP-1） transcription factor subunit （JUN）， MAPK3， protein kinase B1 （AKT1 or Akt1）， tumor protein p53 （TP53）， E1A binding protein p300 （EP300）， Fos proto-oncogene， AP-1 transcription factor subunit （FOS）， tumor necrosis factor （TNF），amyloid beta precursor protein （APP） and cytochrome P450 family 2 subfamily E member 1 （CYP2E1）. Biological function and pathway enrichment analysis showed that JTXZT mainly through xenobiotic metabolic process， oxidation-reduction process， cholesterol metabolic process and other biological processes， regulating phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， MAPK signaling pathway， NAFLD and insulin signaling pathway to play a role in the treatment of NAFLD. The results of molecular docking showed that the active components of JTXZT had a good affinity with the core targets of JTXZT for the treatment of NAFLD.ConclusionJTXZT treats NAFLD through multiple active components， multiple key targets and multiple action pathways.
Keywords：network pharmacology;molecular docking;Jiangtang Xiaozhi tablets;non-alcoholic fatty liver disease （NAFLD）;quercetin;mitogen-activated protein kinase （MAPK）;phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）
Abstract：ObjectiveBased on database mining， the high-frequency compatibility of Caryophylli Fols as the core in formulas for treating diarrhea was analyzed， and the network pharmacology was used to elucidate the mechanism of the core drug group containing Caryophylli Fols in the treatment of diarrhea.MethodThe online database of traditional Chinese medicine （TCM） was intelligently crawled by Python 3.8.1 programming， and the compatibility rules of Caryophylli Fols were analyzed， and the TCM with support≥0.30， confidence≥0.90 and lift≥1.00 was set as the core drug group of Caryophylli Fols. The components were searched and screened by TCM Systems Pharmacology Database and Analysis Platform （TCMSP）， and the disease targets were collected in Therapeutic Target Datebase （TTD）， GeneCards and DisGeNET database with "Diarrhea" as the key word. The network diagram of "TCM-ingredients-potential targets" was constructed by Cytoscape 3.7.1 software， and the network of protein-protein interaction （PPI） was constructed by STRING 11.0. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis of potential targets was analyzed by R language， and the components of the core drug group were preliminarily verified and evaluated by Discovery Studio Client 2016 software.ResultA total of 155 formulas containing Caryophylli Fols for treating diarrhea were screened， involving 54 TCMs. The analysis of association rules showed that Caryophylli Fols was strongly associated with Myristicae Semen， Glycyrrhizae Radix et Rhizoma， Aucklandiae Radix and Atractylodis Macrocephalae Rhizoma in the treatment of diarrhea. The core drug group composed of these five TCMs involved 119 kinds of TCM ingredients and 114 potential targets， of which 104 potential targets were distributed in the nervous system， and the key targets were tumor protein p53 （TP53）， transcription factor activator protein-1 （JUN）， mitogen-activated protein kinase 8 （MAPK8）， interleukin-6 （IL-6）， 90 kDa heat shock protein αA1 （HSP90AA1） and so on. GO enrichment analysis mainly involved biological processes such as the regulation of neurotransmitter levels， blood circulation， hormone-mediated signal pathway and regulation of chemical synaptic transmission. IL-17 signal pathway， helper T cell 17 （Th17） cell differentiation， epidermal growth factor receptor and salmonella infection in KEGG pathways were closely related to the treatment of diarrhea. Molecular docking showed that the key target protein had high affinity with quercetin， kaempferol and β-sitosterol.ConclusionThe multi-components， multi-targets and multi-pathways involved in the core drug group of Caryophylli Fols are closely related to inflammation and nervous system， so it is speculated that it may treat diarrhea by repairing intestinal shielding integrity and regulating the levels of neurotransmitters.
Abstract：ObjectiveTo explore the effect of chemical compound of aconitum alkaloid on the lipopolysaccharide （LPS）-induced inflammatory response of RAW264.7 macrophages and investigate its mechanism.MethodThe chemical compounds of Aconitum Kusnezoffii Reichb were collected from TCMSP database with consideration of oral bioavailability （OB）≥30% and drug-likeness （DL）≥0.18. The potential targets of each chemical component were predicted with use of Pubchem database and Swiss Target Prediction database. Rheumatoid arthritis （RA） targets were collected from GeneCards database and selected by intersection screening. Gene ontology （GO） classification enrichment and Pathway enrichment analysis were carried out with use of DAVID database. Cytoscape was used to construct "Chemical Compound-Potential Targets-Pathway-Disease" network. Protein-protein interaction （PPI） network was constructed by using STRING database and Cytoscape software. RAW264.7 macrophages were stimulated by LPS to establish macrophage inflammation model in vitro. Western blot was used to detect the effects of chemical compounds on the expression of tumor necrosis factor-α （TNF-α） and cyclooxygenase-2 （COX-2） in RAW264.7 cells induced by LPS， as well as on the expression of JAK kinase and nuclear transcription factor- kappa B （NF-κB） signal pathway.ResultA total of 27 chemical compounds were obtained by searching TCMSP database and consulting literature （OB≥30%， DL≥0.18）. 12 chemical compounds were obtained after screening. 177 potential targets were obtained after database prediction and screening， and 97 targets were obtained as potential targets for the treatment of RA after intersection between 177 potential targets and 4 329 RA targets. A total of 32 biological processes （BP）， 5 cellular components （CC）， and 12 molecular functions （MF） were enriched by DAVID database. The construction of network topology map showed that different chemical compounds can act on the same target and the same chemical compound can also act on different targets in the treatment of RA. Aconitum alkaloid can be connected with the same pathway through different targets or with different pathways through the same target， indicating that different targets may have synergistic effect， which fully reflected the complex multi-compound， multi-targets and multi-pathways mechanism. Different concentrations of LPS in stimulation （0-200 μg·L-1） can significantly up-regulate the expression of COX-2 protein in RAW264.7 macrophages （P<0.05）， indicating that the inflammatory model was successful. Compared with the normal group， the expression of TNF-α and COX-2 protein in the inflammatory model of RAW264.7 cells increased significantly（P<0.05）， while the expression of TNF-α and COX-2 protein in bulleyaconitine A（BLA）， songorine， yunaconitine and karacoline groups decreased in varying degrees compared with the model group （P<0.05）. Compared with the normal group， the expression of IRAK4， NF-κB， JAK1 and STAT3 in the inflammatory model of RAW264.7 cells were significantly increased （P<0.05）， while such levels in BulleyaconitineA， songorine， yunaconitine and Karacoline groups were significantly lower than those in the model group（P<0.05）.ConclusionBased on systematic pharmacology and in vitro experiments， the related targets and signal pathways were analyzed to provide new insights into the pathogenesis of RA， reveal the molecular mechanism of aconitum alkaloid in the treatment of RA， and provide new ideas for the application of Mongolian medicine in modern medicine.
Abstract：ObjectiveTo explore the potential targets and mechanism of action of "Clematis Radix et Rhizoma-Trichosanthis Radix" based on network pharmacology.MethodChinese Medicine System Pharmacology Analysis Platform（TCMSP） was used to screen out active ingredients and corresponding target proteins of Clematis Radix et Rhizoma and Trichosanthis Radix according to oral bioavailability（OB） and drug likeness（DL），cancer disease targets were screened out using GeneCards and OMIM databases，R language software was used to screen out common targets of clematis，trichosanthin and cancer diseases， Cytoscape 3.7.2 software was used to construct a network map of "drug-active ingredient-disease-target"， STRING database was used to draw protein protein interaction（PPI）of common target proteins， R language software was used to perform enrichment analysis of gene ontology（GO） functions and Kyoto encyclopedia of genes and genomes（KEGG） channels on effective targets.ResultA total of 9 effective active ingredients were obtained from Clematis Radix et Rhizoma-Trichosanthis Radix powder pair. A total of 31 target genes were searched，and 814 relevant target genes were searched from cancer diseases. The two kinds of relevant target genes were matched to obtain 9 common target genes，which mainly involved endopeptidase，cysteine-type endopeptidase activities involving in the apoptosis process and cancer necrosis factor receptor superfamily binding and other biological processes，and played a role in the treatment of cancers by regulating apoptosis，measles，hepatitis B，kaposi sarcoma-associated herpesvirus infection，p53，interleukin-17（IL-17），tumor necrosis factor（TNF） and many other pathways.ConclusionThe mechanism of Clematis Radix et Rhizoma-Trichosanthis Radix in the treatment of cancer is preliminarily studied. Clematis Radix et Rhizoma-Trichosanthis Radix has multiple active ingredients and can play a role in treating cancer through multiple targets and multiple pathways.
Keywords：internet pharmacology;Clematis Radix et Rhizoma;Trichosanthis Radix;anticancer;mechanism;targets
Abstract：This study aims to investigate the etiology， pathogenic properties and pathogenic characteristics of corona virus disease-2019 （COVID-19） in traditional Chinese medicine（TCM）， so as to provide ideas for clinical treatment based on syndrome differentiation. Efforts were made to retrive relevant literature concerning clinical studies， theoretical discussions and TCM diagnosis and treatment schemes issued by the state and various provinces， municipalities， autonomous regions and municipalities directly under the central government in relation to TCM from China Knowledge Network（CNKI） and Wanfang Database， and to analyze and summarize the etiology， pathology， theoretical viewpoints， clinical symptoms and signs， syndrome differentiation and medication rules. Currently， the common understanding of the etiology of COVID-19 in the field of TCM is the infection of "pestilential pathogen". However， there is a dispute over cold and heat or mixed understanding of cold and heat in terms of pathogenic attributes. The pathogenic factors are different from each other in dampness， toxin， dryness， fire （heat）， wind， filth， depression， etc. There are various understandings on the pathogenesis including dampness， cold， heat， toxin， stasis， phlegm， stagnation， knot， dryness， filth， deficiency， blocking， collapse and asthma， etc. The etiology and pathogenesis are often mixed up. Integration of cold and heat， dryness and dampness， and other contradictory pathogens or pathogenesis is widely seen， which lacks the logicality of theoretical systems， and does not in line with the thinking characteristics of TCM on the etiology， pathogenesis， and syndrome differentiation of exogenous diseases. The main idea of medication in treatment is to diffuse the lung， clear away heat， eliminate dampness， resolve phlegm and repel foulness with aromatics. Maxing Shigantang is used as the core prescription. Chosen warm acrid drugs are mainly the ones with the effect of fragrance， removing dampness， resolving phlegm， and invigorating spleen. They are not the ones with the effects of warming yang and dissipating cold， but the combination of cold and heat， suggesting the complexity of etiology and pathogenesis. COVID-19 is categorized as plaque in TCM， and its etiology is "pestilential pathogen". This pestilential pathogen possesses not only the basic properties of toxin and filth， but also the characteristics of dampness， heat and wind. Throughout the course of the disease， phlegm， stasis， stagnation and other secondary pathogenic factors also occur. The evolution of pathogenesis is characterized by depression， blocking， and deficiency. There are more evidences that the pestilential pathogen of COVID-19 belongs to heat property no matter in the aspects of clinical manifestation， transmission law （syndrome differentiation at different stages）， or in compatibility of medication.
Keywords：corona virus disease-2019 （COVID-19）;etiology of traditional Chinese medicine（TCM）;pathogenic properties;pathogenic characteristics
Abstract：Malignant tumors are important diseases that threaten human health. Although targeting and immunotherapy have been gradually applied in the treatment of malignant tumors in recent years， which can alleviate the suffering of patients to a certain extent， there are still problems of large adverse reactions and easy drug resistance. At present， chemotherapy is still the main method for the treatment of malignant tumors. While killing tumor cells， chemotherapy also damages normal cells， which often leads to drug toxicity， such as bone marrow suppression， gastrointestinal adverse reactions， liver and kidney function damage， and oral mucosal reactions. Although modern medicines have a certain effect on the toxicity of chemotherapy drugs， there are still limitations. Traditional Chinese medicine（TCM） has a long history of treating malignant tumors， and considers that chemotherapy is a drug with toxin invading the body， exacerbating the "deficiency"， "toxin" and "stasis" of the body， causing damage to Qi， blood and organs， especially in spleen， stomach， liver and kidney， and leading to bone marrow suppression， liver and kidney function injury and other adverse reactions. Studies have confirmed that the use of TCM treatment has a better clinical efficacy. Therefore， new therapies shall be explored based on the basic theory of traditional Chinese medicine. As the core part of the theoretical system of TCM， Viscera-state doctrine is closely related to looking， listening， questioning and feeling the pulse of TCM， and has constantly developed and improved. It has important significance in guiding diagnosis and treatment of diseases. This study is guided by viscera-state doctrine of TCM and based on the etiology and pathogenesis of TCM. It starts with the clinical manifestations of common drug toxicity of chemotherapy drugs， such as bone marrow suppression， gastrointestinal adverse reactions， liver and kidney function damage， oral mucosal reactions， which are external signs of the toxicity of chemotherapeutic drugs， and associates pathological manifestations of viscera to physiological functions. From elephants and Tibetans， it systematically summarizes the viscera characteristics of various common chemotherapeutic drugs and provides new ideas and methods for clinical use of TCM in treating the toxicity of chemotherapeutic drugs， so as to promote the application of viscera-state doctrine in diagnosis and treatment of diseases.
Keywords：viscera-state doctrine;chemotherapeutic drug toxicity;bone marrow depression;gastrointestinal adverse reactions;liver and kidney injury;oral mucosal reaction
Abstract：Heart failure is a complex clinical syndrome，which is the final result of compensatory failure of heart injury caused by various reasons. Long-term persistent cardiac stress leads to mitochondrial dysfunction，which in turn further damages cardiomyocytes and leads to disease progression. Timely removal of damaged mitochondria in cardiomyocytes and maintaining a good living environment of viable mitochondria is not only an effective means to protect cardiomyocytes，but also a new way to prevent and treat heart failure and ventricular remodeling. Mitochondrial quality control is a series of cellular activities for mitochondria to maintain their structural and functional stability，including oxidative stress response，regulation of mitochondrial dynamics，mitochondrial autophagy，intracellular calcium regulation and so on. Traditional Chinese medicine（TCM） mostly uses drugs of replenishing Qi and activating blood circulation in the treatment of chronic heart failure，and Qi and mitochondria are similar in function. According to TCM，the performance of the body as "static，descending and inhibitory" in the case of Qi deficiency can also be compared with the energy defect of mitochondria. The classical method of tonifying qi and activating blood circulation in TCM can be applied here. In recent years，TCM takes mitochondria as the target and carries out many related experimental studies from the point of view of myocardial energy supply. It is found that Chinese herbs for replenishing Qi and activating blood circulation can participate in regulating the quality control mechanism of intracellular mitochondria with multiple targets and links. It is proved by experiments that Chinese herbs for replenishing Qi and activating blood circulation can exert myocardial protective effect through this mechanism.
Keywords：replenishing Qi and activating blood circulation;heart failure;mitochondrial;intervention
Abstract：Moringa oleifera is a typical tropical multi-functional fast-growing tree species， which is native to India and now widely planted in various tropical regions. After some research and textual research， the records of M. oleifera in China can be traced back to the The Bower Manuscript（volume Ⅱ）（about the 4th—6th century A.D.） unearthed in Kuqa， Xinjiang. M. oleifera contains a variety of active ingredients such as flavonoids， alkaloids， glycosides， organic esters and rich nutrients， which has outstanding medicinal and economic value. As a result， M. oleifera is widely used in food additives， water purification agents， medicine and health care and other fields. In 2012， the Ministry of Health approved M. oleifera as a new resource food. In the current trend of medicine diet and health preservation of traditional Chinese medicine， M. oleifera stands out， which not only expands the direction for the development of health products， but also enriches the development demand of traditional Chinese medicine in our country. However， in our country， the research on M. oleifera is mainly focused on the extraction of chemical components， analysis of nutritional components， consumption and content determination， and the research on its composition and pharmacological action is one-sided. For this purpose， this paper briefly reviewed the active components， hypoglycemic and treatment of diabetic complications， hypolipidemic， antioxidant， anti-inflammatory and applied research status of M. oleifera， and looked forward to the future development and utilization of M. oleifera leaves in China.
Abstract：Plantaginis Semen is a traditional Chinese medicine （TCM） commonly used in China， which is one of the authentic medicinal materials in Jiangxi. It has great development prospects. However， the current research on Plantaginis Semen is not in-depth enough， mainly involving chemical components and pharmacological activities. There are few researches on processing and variety of Plantaginis Semen. In order to further develop and utilize the resources of Plantaginis Semen， we summarized 4 varieties that have been studied more at present， the processing contents of Plantaginis Semen in ancient and modern literature were consulted and sorted out， and its processing historical evolution were summarized. The influences of different processing technologies and methods on the chemical composition and pharmacological effects of Plantaginis Semen were analyzed， the possible processing mechanism was discussed. Meanwhile， and the quality evaluation methods of Plantaginis Semen varieties included in the 2020 edition of Chinese Pharmacopoeia were summarized. The author mainly analyzed the researches status of Plantaginis Semen and its decoction pieces in the three aspects of variety， processing and quality evaluation， and summarized its current major problems such as insufficient use and development of varieties， unclear processing mechanisms， and undetermined quality evaluation standards. And combined with the national standardization project of TCM to carry out the prospect and analysis for it， in order to solve the problems in the actual production and use of Plantaginis Semen， and provide reference for its further development， production of the high-quality decoction pieces， analysis of the processing mechanism， and establishment of the quality control system.
Keywords：Plantaginis Semen;processing;quality evaluation;varieties;historical evolution;genuine medicinal materials;standardization of traditional Chinese medicine （TCM）
Abstract：Cisplatin， as one of the commonly used broad-spectrum anti-tumor drugs in clinical practice， is used to treat testicular cancer， ovarian cancer， head and neck cancer， bladder cancer， lung cancer， cervical cancer and other solid cancers. It has obvious curative effect but strong toxic and side effect， and is easy to cause great damage to the body. The toxic reaction may involve serious toxic damages to different organs， and induce nephrotoxicity， hepatotoxicity， ototoxicity， cardiotoxicity， neurotoxicity and other toxicity. Animal experiments have shown that the toxic damage induced by cisplatin is the result of many factors in a time-and dose-dependent manner. In the course of clinical use， the therapeutic dose of cisplatin is also greatly limited due to toxic damage， which seriously affects the quality of life in patients. Therefore， it is the main research direction to find a suitable treatment plan or to use drugs in combination with cisplatin to reduce toxicity and increase efficiency. With the increasing clinical participation of traditional Chinese medicine（TCM）， TCM has shown its unique advantages in treating diseases， and can effectively reduce the cisplatin chemotherapy-induced toxic reaction by improving the oxidative stress state of the body， inhibiting normal apoptosis and inflammatory injury， activating autophagy， regulating the abnormal expression of drug transporters， etc. In this paper， the mechanism of cisplatin-induced toxic damage to various organs and the mechanism of TCM in prevention and treatment of cisplatin-induced toxic damage were summarized in detail， including the dose and mechanism of cisplatin-induced toxic damage to different organs， the effective treatment dose， combined medication mode and prevention and treatment mechanism of combined application of TCM and cisplatin， in order to provide a basis for rational application and clinical medication of TCM combined with chemotherapy drugs such as cisplatin.
Keywords：traditional Chinese medicine;cisplatin;prevention and control;toxic damage;strengthening body resistance and eliminating pathogenic factors
Abstract：Rheumatoid arthritis （RA） is a chronic and systemic autoimmune disease with aggressive and symmetrical polyarthritis as the main clinical manifestations. The exact pathogenesis is unknown. Its basic pathological changes include chronic inflammation of the joint synovium， increased joint cavity effusion， pannus formation， gradual cartilage damage and bone erosion， eventually leading to joint deformity and loss of function. It has been found that the onset and development of RA are related to heredity， environment and other factors. The drugs for RA mainly include non-steroidal anti-inflammatory drugs （NSAIDs）， corticosteroids， disease-modifying anti-rheumatic drugs （DMARDs） and biological agents. However， long-term use of these drugs can cause a variety of side effects and adverse reactions， such as myocardial infarction， peptic ulcer， poor wound healing， and liver and kidney dysfunction. In addition， natural medicines have a good application prospect because of their various pharmacological activities and few side effects. Quercetin is a flavonoid found in Morus alba and tetrandrine， with diverse pharmacological activities， including cardiovascular diseases， joint movement， tumor immunology and so on. Not only have the clinical trials shown good efficacy of quercetin， but the experimental studies have also proven that quercetin can improve RA by reducing inflammatory response， inhibiting the formation of synovial pannus， synovial hyperplasia， neutrophil NETs formation， osteoclast function， regulating Th17/Treg balance and other mechanism. In this article， we will briefly summarize the regulatory mechanism of quercetin and discuss the complexed effect of quercetin on rheumatoid arthritis.