Abstract：ObjectiveTo investigate the effects of Da Jianzhongtang on substance P （SP）， mast cells （MC）， Toll like receptor 2 （TLR2）， TLR4 on MC model and nuclear transcription factor （NF）-κB p65 in visceral pain rats with irritable bowel syndrome （IBS）， and explore its mechanism of action on IBS visceral pain.MethodForty-eight 3-day-old SD rats were randomly divided into 6 groups： the control group （control）， irritable bowel syndrome group （IBS）， ketotifen group （Ketotifen，0.18 mg·kg-1）， Da Jianzhongtang low， medium and high dose groups （DJZT-L， DJZT-M， DJZT-H，2.16，1.08，0.54 g·kg-1）， with 8 rats in each group. Intragastric administration lasted for 2 weeks. Maternal separation method was used to establish the IBS visceral pain model in rats. The visceral sensitivity of rats was evaluated at 60， 40 and 20 mmHg （1 mmHg≈0.133 kPa） with Abdominal wall withdrawal response （AWR） scale. SP and NF-κB p65 protein expression levels in colon tissue were detected with Western blotting technique. TLR2 and TLR4 proteins on mast cell membrane were detected by immunofluorescence staining. The degranulation rate of mast cells in colon tissue was detected by toluidine blue staining.ResultCompared with normal rats， AWR scores of model rats significantly increased at 60， 40， and 20 mmHg pressure （P<0.05，P<0.01）， the degranulation rate of mast cells in colon tissue and SP protein expression in colon tissue significantly increased （P<0.01）， TLR2， TLR4， and nuclear NF-κB p65 expression on mast cell membrane significantly increased （P<0.01）. Compared with model rats， the AWR scores of DJZT-H group （pressure of 40， 20 mmHg） and DJZT-M group （pressure of 60， 40， 20 mmHg） significantly decreased. Meanwhile， the degranulation rate of colon mast cells， and the SP， TLR2， TLR4， and NF-κB p65 expression also significantly decreased （P<0.05，P<0.01）.ConclusionDa Jianzhongtang can affect mast cell activity and finally decrease visceral pain of IBS rats by down-regulating SP in colon tissue.
Abstract：ObjectiveTo investigate the effect of Guizhi Fulingwan on ovulation dysfunction in rats with polycystic ovary syndrome with insulin resistance （PCOS-IR） induced by letrazole combined with high fat emulsion.MethodA total of 72 female SD rats were randomly divided into control group， model group， metformin group and Guizhi Fulingwan low， medium and high dose groups， with 12 rats in each group. Except for control group， rats were given letrozole 0.001g·kg-1 combined with high-fat emulsion 15 mL·kg-1 for 21 consecutive days to establish model of PCOS-IR. Guizhi Fulingwan low， medium and high-dose groups were administrated with Guizhi Fulingwan 0.31， 0.62， 1.24 g·kg-1 respectively， metformin group was administrated with metformin 0.27 g·kg-1， control group and model group were administrated with 12 mL·kg-1 of normal saline daily for 30 days. Hematoxylin-eosin（HE） staining was used to observe ovarian tissue pathology morphology， and enzyme-linked immunoassay method （ELISA） was used to detect serum follicle stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， fasting insulin （FINS） level，and LH/FSH and insulin resistance index （HOMA-IR） were calculated． Western blot was used to detect the expression levels of autophagy key molecular Atg6 yeast homologue （Beclin-1）， autophagy related gene 5（Atg5）， microtubule associated protein light chain 3 （LC3） Ⅱ proteins in the phosphatidylinositol 3-kinase/protein kinase B/rapamycin target protein （PI3K/Akt/mTOR） signaling pathway and autophagy related indicators in rat ovarian tissue. Beclin-1 and LC3Ⅱ protein expressions were detected by immunohistochemistry （IHC）.ResultCompared with control group， the thickness of follicles and follicular granulosa cells in the ovary of the model group also decreased， and the number of corpus luteum significantly decreased， while the white membrane thickness of the ovary increased， and the number of atresia follicles and cystic dilatation follicles increased significantly. Serum T， LH， LH/FSH， FINS， FINS， HOMA-IR were significantly increased （P<0.01）. Phosphorylated （p） -PI3K， p-Akt， and p-mTOR proteins in ovarian tissue were all decreased （P<0.05，P<0.01）. The relative expression levels of autophagy-related protein LC3Ⅱ and Beclin-1 were significantly increased （P<0.05，P<0.01）. Compared with model group， the number of follicles in the low， medium and high dose Guizhi Fulingwan group and the metformin group decreased， the number of follicles in atresia and atresia increased， and the follicular granulosa cell layer thickness increased. Serum T， LH， LH/FSH， FINS and HOMA-IR of Guizhi Fulingwan group were significantly decreased （P<0.05，P<0.01）， and serum FINS and HOMA-IR of metformin group were significantly decreased （P<0.01）. The expressions of p-PI3K， p-Akt， and p-mTOR proteins were increased （P<0.05，P<0.01）. The expression levels of LC3Ⅱ， Atg5 and Beclin-1 in the medium and high dose groups were significantly decreased （P<0.01）.ConclusionGuizhi Fulingwan can activate the PI3K/Akt/mTOR signaling pathway of granular cells， inhibit excessive autophagy of granular cells， improve ovarian function and insulin resistance， and restore ovulation， and the effect is better with high dose.
Abstract：ObjectiveTo observe the effect of Zuoguiwan on bone metabolism and Wnt/β-catenin signaling pathway in ovariectomized osteoporotic rats model， and to explore the molecular biological mechanism of Zuoguiwan in the prevention and treatment of osteoporosis.MethodThe rat model of postmenopausal osteoporosis was established by bilateral ovariectomy， 60 female SD rats were randomly divided into sham operation group， model group， positive group （estradiol valerate tablet 0.05 mg·kg-1·d-1） and low， middle and high dose groups of Zuoguiwan （5.5，11，22 g·kg-1·d-1）.After successful establishment of the model in the 13th week， intragastric administration （ig） was given once a day for a total of 12 weeks. After administration， the histomorphological changes of femur in rats were observed by hematoxylin-eosin （HE） staining， the bone mineral density （BMD） and bone mineral content（BMC） of femur were measured by dual energy X-ray apparatus， and the biomechanical properties of bone were measured by MTS Acumen3 biomechanical testing system. The contents of bone alkaline phosphatase （BALP）， bone glaprotein（BGP），estradiol （E2） ，and tartrate-resistant acid phosphatase （TRAP）， type Ⅰ procollagen N-terminal propeptide （PINP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein level of Wnt2，β-catenin，low density lipoprotein related receptor protein 5 （LRP5） and the phosphorylation level of glycogen synthase kinase-3β（GSK-3β） in rat tibia.ResultCompared with sham operation group， the maximum load and stiffness of BMD，BMC， in the model group decreased significantly（P<0.01）， the contents of E2 and PINP in serum decreased significantly（P<0.01）， the content of BALP，BGP，TRAP increased significantly（P<0.01）， the expression levels of Wnt2，p-GSK-3β Ser9，LRP5 and β-catenin protein in bone tissue decreased significantly（P<0.01）， the trabecula of femur became thinner and thinner， the number of bone trabeculae decreased. Compared with model group， the maximum load and stiffness of BMD，BMC， in estradiol group and Zuoguiwan group were significantly increased （P<0.05，P<0.01）， the contents of serum E2 and PINP were significantly increased （P<0.05，P<0.01）， the content of BALP，BGP，TRAP was significantly decreased （P<0.01）， and the expression level of Wnt2，p-GSK-3β Ser9，LRP5， β-catenin protein in bone tissue was significantly increased （P<0.05，P<0.01） ， the trabeculae of femur became thicker， the number increased， the structure was basically clear.ConclusionZuoguiwan has a certain preventive and therapeutic effect on osteoporosis in ovariectomized rats， and its mechanism may be related to increasing the level of estrogen， activating Wnt/β-catenin signaling pathway， up-regulating the expression of Wnt2 and LRP5 protein， inhibiting the activity of GSK-3β， reducing the degradation of β-catenin， coordinating the dynamic coupling balance between bone formation and bone resorption， correcting the disorder of bone metabolism and improving bone morphology.
Keywords：Zuoguiwan;postmenopausal osteoporosis（PMOP）;Wnt/β-catenin signaling pathway;glycogen synthase kinase-3β（GSK-3β）;low density lipoprotein receptor related protein 5（LRP5）;bone metabolism
Abstract：ObjectiveTo explore the effect of Trichosanthis Fructus-Allii Macrostemonis Bulbus medicine on the proliferation and autophagy levels of aortic plaque vascular smooth muscle cells （VSMCs） in ApoE-/- mice with atherosclerosis （AS）.MethodA total of 40 ApoE-/- mice were fed with high-fat diet to replicate AS animal models. They were randomly divided into model group， Trichosanthis Fructus-Allii Macrostemonis Bulbus group， rapamycin group and atorvastatin group， and 10 mice with normal diet C57BL/6J mice were the blank group. The blank group and the model groups were given normal saline by gavage， while Trichosanthis Fructus-Allii Macrostemonis Bulbus group， rapamycin group and atorvastatin group were given corresponding drugs by gavage for 8 weeks. After the experiment， the mice were sacrificed. Total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） levels were detected by the Microplate reader， the ratio of the aortic plaque area to the total area was observed and measured by staining with aortic gross oil red O. Western blot method was used to detect the proliferation-related protein proliferating cell nuclear antigen （PCNA） and α-smooth muscle actin （α-SMA） levels of VSMCs in the aortic media. Transmission electron microscopy was used to observe the autophagosomes of VSMCs and detect the expressions of VSMCs autophagy-related proteins Beclin-1， light chain proteinⅡ （LC3Ⅱ） and p62.ResultCompared with the model group， the Trichosanthis Fructus-Allii Macrostemonis Bulbus group showed significant reduction in the aortic lipid accumulation and plaque area of AS mice and the levels of TC， TG， LDL-C （P<0.01） and increase of HDL-C （P<0.05）. Trichosanthis Fructus-Allii Macrostemonis Bulbus significantly reduced the levels of proliferation-related antigens PCNA and α-SMA in aortic VSMCs （P<0.01）， and inhibited the excessive proliferation of VSMCs. Trichosanthis Fructus-Allii Macrostemonis Bulbus significantly up-regulated Beclin-1 and LC3Ⅱ in aortic VSMCs protein expression， decreased p62 accumulation （P<0.01）， increased the expressions of VSMCs autophagosomes， and increased the autophagy level of VSMCs.ConclusionTrichosanthis Fructus-Allii Macrostemonis Bulbus regulates blood lipid levels in AS mice， and inhibits the excessive proliferation of aortic VSMCs and plaque formation in the aorta of AS mice. The mechanism may be related to the up-regulation of the autophagy activity of VSMCs.
Abstract：ObjectiveTo observe the effect of modified Si Junzitang on the level of lactic acid in gastric mucosa and the expression of Carboxylic acid transporter 1（MCT1）， monocarboxylic acid transporter 4（MCT4）， and extracellular matrix metalloproteinase inducer （CD147）in rats with gastric precancerous lesions（GPL）.MethodSeventy-four SD male rats were randomly divided into normal group （12 rats） and model group （62 rats）. N-methyl-N'-nitro-N-nitrosoguanidine（MNNG）-ammonia compound method was used to establish GPL rat models， and at the 9th week， the model rats were randomly divided into model group， folic acid group（2.7 mg·kg-1）， modified Si Junzitang high， medium and low dose groups（12.6， 6.3， 3.15 g·kg-1）， with 12 rats in each group. After intragastric administration for 12 weeks， the general conditions of the rats were observed. Hematoxylin-eosin（HE）staining was used to observe the histopathological changes of gastric mucosa in rats， chemical colorimetry was used to detect the content of lactic acid in gastric mucosa； immunohistochemistry and real-time polymerase chain reaction（Real-time PCR）were used to detect MCT1， MCT4， CD147 protein and mRNA expression in gastric mucosal tissues.ResultModified Si Junzitang significantly improved the pathological manifestations in GPL rats such as gastric mucosal epithelial gland structure， disorder of arrangement and cell atypia. Compared with the normal group， the lactic acid content of the gastric mucosa tissue in the model group increased significantly（P<0.01）， and the protein and mRNA expressions of MCT1， MCT4， CD147 significantly increased（P<0.05， P<0.01）. Compared with the model group， the lactic acid content in each dose group of modified Si Junzitang was significantly reduced（P<0.05， P<0.01）， and the protein expression levels of MCT4 and CD147 were also significantly reduced in each dose group of modified Si Junzitang（P<0.05， P<0.01）. The mRNA expression of MCT4 was significantly reduced in the middle and high dose groups（P<0.05， P<0.01）， and the mRNA expression of CD147 was significantly reduced in the high dose group（P<0.05）. Modified Si Junzitang showed no significant regulatory effect on MCT1.ConclusionModified Si Junzitang can significantly improve the abnormal histopathology of gastric mucosal epithelium in GPL model rats. Its mechanism may be related to down-regulating the overexpression of MCT4 and CD147， inhibiting lactic acid outflow， and improving the acidic microenvironment of gastric mucosal epithelium.
Abstract：ObjectiveTo explore the therapeutic effect of Fuzheng Huayu capsule on nonalcoholic fatty liver fibrosis induced by high trans fatty acid and high sugar diet in mice.MethodForty SPF male C57/B6 mice were randomly divided into 4 groups （normal group， model group， Obelcholinic acid group， and Fuzheng Huayu capsule group）， with 10 mice in each group. Except 10 mice in the normal group， nonalcoholic fatty liver fibrosis was induced by high-fat and high-sugar diet for 24 weeks in the other 30 mice. From the 25th week of modeling， 4 groups received intragastric administration for 4 weeks， once a day： Fuzheng Huayu capsule group 4.8 g·kg-1. Oxycholic acid group 10 mg·kg-1. Model control group and normal group received the same volume of normal saline. Liver tissue and serum samples were collected at the end of the 28th week. The pathological changes of liver tissue of mice in each group were observed by hematoxylin-eosin （HE） staining， the degree of liver fibrosis was observed by Sirius red staining， the degree of lipid deposition was observed by oil red O staining， the content of hydroxypropylamine （Hyp） in liver tissue was determined by alkaline hydrolysis， and the change of triglyceride （TG） in liver tissue was detected by enzyme method. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST） activities and fasting blood glucose （FBG） were detected by kit method， enzyme-linked immunosorbent assay （ELISA） was used to detect fasting Insulin （INS） level and calculate the changes of insulin resistance index （HOMA-IR）， liver fibrosis related mRNA and proteins of were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， Western blot and Immunohistochemistry.ResultCompared with the normal group， the liver tissue in the model group showed significant collagen fiber deposition， at mostly F2-F3 fibrosis stages， with increased number of inflammatory foci in liver tissue， obvious balloon degeneration and fatty degeneration of liver cells， significantly increased contents of Hyp and TG in liver tissue （P<0.01）， significantly increased activities of ALT and AST in serum and levels of FBG， INS and HOMA-IR （P<0.01）， and increased type I collagen （Col-Ⅰ）， Col-Ⅳ， α-smooth muscle agonist protein （α-SMA） and transforming growth factor-β （TGF-β） protein and mRNA in liver tissue. Compared with the model group， the collagen fiber deposition in liver tissue of mice in Fuzheng Huayu capsule group was significantly reduced， at mostly F0-F1 fibrosis stages， with significantly improved balloon-like change of hepatocytes， and significantly reduced number of inflammatory foci in lobules （P<0.05，P<0.01）. Compared with the model group， Fuzheng Huayu capsule can significantly reduce the content of Hyp in liver tissue， the levels of serum ALT and AST， and the expression of Col-Ⅰ， Col-Ⅳ， α-SMA and TGF-β genes and proteins in mice （P<0.05，P<0.01）.ConclusionFuzheng Huayu capsule has a good therapeutic effect on nonalcoholic fatty liver fibrosis induced by high trans fatty acid and high sugar diet in mice.
Abstract：ObjectiveTo observe the effect of modified Shengjiangsan on renal fibrosis in rats with membranous nephropathy （MN） and to explore the mechanism of its complications of renal fibrosis.MethodRats were injected with cationized bovine serum albumin（C-BSA）in the tail vein to establish a rat model of membranous nephropathy. The normal group，model group，modified Shengjiangsan group （27.3 g·kg-1）and benazepril group（10 mg·kg-1）were established in this study. Each group was given corresponding dosage of the drug once a day for 4 weeks of continuous intervention. After the administration，we observed the pathological changes of rat kidneys by the technology of Masson staining， silverhexylamine iodate （PASM） staining， transmission electron microscopy （TEM）， immunofluorescence technology （IF） was used to detect immunoglobulin（Ig）G deposition in rat kidneys. The levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） in rat serum were detected by enzyme-linked immunosorbent assay （ELISA） method. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and immunohistochemistry （IHC） were used to detect the mRNA and protein expression levels of monocyte chemotactic protein 1 （MCP-1）， intercellular adhesion molecule 1 （ICAM-1）， nuclear factor kappa B （NF-κB）， Toll-like receptor 4 （TLR4）， plasminogen activator inhibitor 1 （PAI-1）， transforming growth factor-β1 （TGF-β1）， α-smooth muscle actin （α-SMΑ） and type Ⅳ Collagen （Collagen Ⅳ） in rat kidney tissues.ResultCompared with normal group， the kidney tissue of the model group was obviously fibrotic， the serum levels of IL-1β， IL-6， and TNF-α were significantly increased（P<0.05）， and the expressions of MCP-1， ICAM-1， NF-κB， TLR4， PAI-1， TGF-β1， α-SMA and Collagen Ⅳ mRNA and protein in kidney tissue were significantly increased（P<0.05）. Compared with model group， modified Shengjiangsan and benazepril significantly improved renal fibrosis in rats， reduced the levels of IL-1β， IL-6， and TNF-α in the serum of MN rats（P<0.05）， down-regulated MCP-1， ICAM-1， NF-κB， TLR4， PAI-1， TGF-β1， α-SMA and Collagen Ⅳ mRNA and protein expression in kidney tissue（P<0.05）.ConclusionModified Shengjiangsan can reduce the release and expression of inflammatory factors by down-regulating the TLR4/NF-κB signaling pathway， inhibit renal fibrosis， and reduce renal damage in MN rats.
Abstract：ObjectiveTo investigate the effect of Weiwei Tongtiao decoction on gastric mucosal pathology and the expression level of inhibitor kappa B kinase β（IKKβ） and B-cell lymphoma-2（Bcl-2）in rats with chronic atrophic gastritis （CAG） precancerous lesion.MethodSD rats were randomly divided into normal group， model group， positive drug Weifuchun group， Weiwei Tongtiao decoction high， medium and low dose treatment groups. The rat model of CAG precancerous lesion was prepared by N-methyl-N'-nitro-N-nitrosoguanidine （MNNG）compound modeling method. weiwei Tongtiao decoction high， medium and low dose treatment groups received intragastric administration of 24， 12， 6 g·kg-1 Weiwei Tongtiao decoction respectively， while Weifuchun group received 0.45 g·kg-1 Weifuchun suspension， once per day for 12 weeks. The pathological changes of gastric mucosa of rats were observed by hematoxylin-eosin（HE）staining， and the mRNA and protein levels of IKKβ and Bcl-2 in gastric mucosa of rats were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry（IHC）and Western blot.ResultCompared with the normal group， 100% inherent gland atrophy， mild to severe intestinal metaplasia， and 25% low-grade intraepithelial neoplasia were observed under microscope in model group. All Weifuchun group and Weiwei Tongtiao decoction groups could improve the atrophy of gastric glands， moderate to severe intestinal metaplasia and pathological injury of low-grade intraepithelial neoplasia， especially at high dose group. Compared with the normal group， IKKβ， Bcl-2 mRNA and protein expressions in the gastric mucosa of the model group were up-regulated （P<0.01）. Compared with the model group， the mRNA and protein expressions of IKKβ and Bcl-2 in gastric mucosa of rats in the Weifuchun group and the Weiwei Tongtiao decoction high， medium and low dose groups were down-regulated （P<0.05，P<0.01）， showing a dose-dependent relationship， and such levels in the Weiwei Tongtiao decoction high-dose intervention group were similar to those in normal group.ConclusionWeiwei Tongtiao decoction can improve and even reverse gastric mucosa with CAG precancerous lesions in rats， and its intervention mechanism may be related to down-regulating the expressions of IKKβ and Bcl-2 in gastric mucosa.
Abstract：ObjectiveTo discuss the efficacy of Bushen Huoxue decoction for recovery in patients with intra uterine adhesions （IUA） after trans cervical resection adhesions （TCRA） operation， and to investigate its effect on fibrosis factor.MethodThe 110 patients were randomly divided into two groups by random number table （55 cases for control group and 55 cases for observation group）. The patients in both groups got TCRA， and after the operation， they got estradiol valerate tablets+progesterone capsules. The patients in control group additionally got Jinfengwan before meals， 10 g/time， 2 times/day. Patients in observation additionally got syndrome differentiation and treatment by Bushen Huoxuetang， 1 dose/day. The treatment course was 3 months in both groups， and 6 months' follow-up was recorded. Before and after treatment， menstrual volume， period and cycle were recorded. During the follow-up， pregnancy， ectopic pregnancy and abortion were also recorded. Endoscopy and vagina color Doppler ultrasound were conducted to detect endometrial thickness， uterine volume， resistance index （RI）， pulsation index （PI） and blood flow index （FI）. Scores of IUA and syndrome of kidney deficiency and blood stasis were graded. At the 6th months after treatment， rate of intrauterine re-adhesion was recorded. Levels of transforming growth factor-β1 （TGF-β1）， connective tissue growth factor （CTGF）， matrix metalloproteinase inhibitor-1 （TIMP-1）， platelet-derived growth factor （PDGF）， insulin-like growth factor-1 （IGF-1） and matrix metalloproteinase-9 （MMP-9） were detected， and safety was evaluated.ResultTotal effective rate of clinical efficacy was 96.36% （53/55） in observation group， higher than 83.64% （46/55） in control group （χ2=4.959， P<0.05）. Recovery rate of menstrual volume， period and cycle were 92.73% （51/55）， 90.91% （50/55）， and 94.55% （52/55） in observation group， higher than 72.73% （40/55）， 76.36% （42/55）， and 76.36% （42/55） in control group（χ2=7.698，χ2=4.245，χ2=7.313，P<0.05， P<0.01）. During the follow-up， rate of intrauterine re-adhesions was 23.64% （13/55） in observation group， lower than 43.64% （24/55） in control group （χ2=4.927，P<0.05）. Pregnancy rate was 45.45% （25/55）， higher than 25.45% （14/55） in control group（χ2=4.807，P<0.05）. Score of syndrome of kidney deficiency and blood stasis and IUA scores in observation group were lower than those in control group （P<0.01）. Endometrial thickness， uterine volume， and FI were higher than those in control group （P<0.01）. Levels of RI， PI， TGF-β1， CTGF， PDGF， IGF-1 and TIMP-1 were lower than those in control group （P<0.01）， while level of MMP-9 was higher than that in control group （P<0.01）. No adverse reactions related to traditional Chinese medicine were found.ConclusionBushen Huoxue decoction can promote the recovery of menstruation， increase the thickness of endometrium， improve the blood circulation of uterus， regulate the expression of fibrogenic factors in vivo， prevent and treat intrauterine adhesions， reduce the rate of intrauterine re-adhesions， and improve the rate of pregnancy， with a good comprehensive effect and high safety for clinical use.
Keywords：intra uterine adhesions;hysteroscopic separation of intra uterine adhesions;kidney deficiency and blood stasis syndrome;Bushen Huoxue decoction;intrauterine re-adhesions;fibrotic factors;endometrial repair;pregnancy outcome
Abstract：ObjectiveTo observe the clinical efficacy of addition and subtraction therapy of Jinkui Shenqiwan combined with Buzhong Yiqitang to postmenopausal osteoporosis （PMO） with deficiency of spleen and kidney， and to investigate its regulation effect on immune inflammatory factors.MethodOne hundred and sixty patients were randomly divided into observation group and control group， with 80 cases in each group. Both groups got comprehensive western medicine treatment measures. Patients in control group additionally got Zhuanggu Zhitong capsule， 4 capsules/time， 3 times/day. Patients in observation group additionally got addition and subtraction therapy of Jinkui Shenqiwan combined with Buzhong Yiqitang， 1 dose/day. The treatment was continued for 24 weeks. Before and after treatment， lumbar L2-4 bone mineral density （BMD） was detected by Dual energy X-ray absorptiometry （DXA） and lumbar BMD was detected by quantitative CT （QCT）. Scores of traditional Chinese medicine（TCM） syndromes and Chinese osteoporosis-targeted quality of life questionnaire （COQOL） were graded. Levels of Estradiol （E2）， type Ⅰ procollagen amino terminal pro peptide （PINP）， serum osteocalcin （OC）， osteoprotegerin （OPG）， type Ⅰ collagen cross-linked C-terminal peptide （S-CTX）， tartrate resistant acid phosphatase （TRACP） and urinary pyridinoline （PYD） were detected. Levels of CD4+ T cells， CD8+ T cells， interleukin-17 （IL-17）， tumor necrosis factor-α （TNF-α）， γ-interferon（IFN-γ） and interleukin-4 （IL-4） were calculated. The proportion of T helper cell （Th）17 and regulatory T cell （Treg） in CD4+ T cells was calculated. Besides， the safety was evaluated.ResultBone density was detected by DXA in observation group， and its T-value and bone density detected by QCT were all higher than those in control group （P<0.01）. After treatment， scores of TCM syndrome and COQOL were lower than those in control group （P<0.01）. Levels of PINP， OC， S-CTX， TRACP and PYD/Cr were all lower than those in control group （P<0.01）. Levels of OPG， CD8+ and Treg were higher than those in control group （P<0.05）， levels of Th17， Th17/Treg， CD4+/CD8+， IL-17， TNF-α and IFN-γ were lower （P<0.01）， and levels of IL-4 and E2 were higher than those in control group （P<0.01）. The clinical efficacy in observation group was better than that in control group （Z=2.103， P<0.05）.ConclusionOn the basis of calcium and vitamin D supplementation， Jinkui Shenqiwan combined with Buzhong Yiqitang can improve levels of E2 and bone density， reduce clinical symptoms， improve quality of life， regulate bone metabolism index and immune inflammation reaction， with better clinical efficacy and safety.
Keywords：postmenopausal osteoporosis;deficiency of spleen and kidney;Jinkui Shenqiwan;Buzhong Yiqitang;bone mineral density;bone metabolism index;T cell subsets;T helper cell （Th）17;regulatory T cell （Treg）
Abstract：ObjectiveTo explore the clinical efficacy of Shugan Lidan decoction（SLD） combined with laparoscopic cholecystectomy on acute calculous cholecystitis（ACC），and explore its mechanism based on network pharmacology.MethodIn a retrospective analysis， 121 patients with ACC were divided into laparoscopic cholecystectomy+SLD group （observation group， 68 cases） and laparoscopic cholecystectomy group（control group，53 cases）. The postoperative recovery of the patients （time to first exhaust，time to temperature recovery，antibiotic use time and hospitalization time），serum inflammatory factor levels ［white blood cell count（WBC），C-reactive protein（CRP），interleukin-6（IL-6）］，immune index levels［claster of differentiation（CD）3+，CD4+/CD8+，immunoglobulin M（IgM）］ and safety were compared between these two groups. The TCMSP，BATMAN-TCM and TCMIP databases were used to collect all chemical components and targets of SLD. GeneCard and OMIM databases were combined to search ACC-related targets，and then the intersection ones of SLD-related targets and ACC-related targets were extracted to obtain the potential action targets of SLD for treatment of ACC. The STRING database platform was used to establish and analyze the protein-protein interaction （PPI） network，and Bioconductor software package was used for Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment of the targets.ResultThe time to first exhaust，antibiotic use time and hospitalization time of observation group were shorter than those of control group，and the differences were statistically significant（P<0.05）. After treatment，the postoperative WBC，CRP，IL-6，CD4+/CD8+ and IgM in the two groups of patients were lower than those before treatment，and the postoperative CD3+ was higher than that before treatment，with statistically significant differences（P<0.05）. The postoperative WBC，CRP，IL-6，CD4+/CD8+ and IgM in the observation group were lower than those in control group，and the CD3+ was higher than that of control group，with statistically significant differences（P<0.05）. There was no statistical difference in adverse reactions between the two groups. Totally 159 components in SLD were screened，which acted synergistically on key targets such as IL-6，vascular endothelial growth factor A（VEGFA），insulin（INS），and epidermal growth factor receptor（EGFR），and participated in the regulation of HIF-1 signaling pathway，EGFR tyrosine kinase inhibitor resistance and PI3K-Akt signaling pathway in the treatment of ACC.ConclusionSLD may regulate HIF-1 pathway and other signaling pathways by acting on IL-6，VEGFA，INS，EGFR and other targets，thereby reducing postoperative inflammatory factors，improving immune function，and promoting postoperative recovery in patients with ACC.
Abstract：ObjectiveTo observe the efficacy of addition and subtraction therapy of Danshenyin combined with Wendantang in the treatment to stable angina pectoris （SAP） with stagnation of phlegm and blood stasis， and to explore its protection mechanism for myocardial ischemia.MethodOne hundred and thirty-two patients were randomly divided into control group and observation group equally. Finished the 63 cases study both in control group and observation group after dropout， loss of follow-up and withdrawal. Patients in control group and observation group got antianginal drugs and the treatment of drug therapy to control the risk factors. All patients were treated with anti-angina drugs and risk factors control drugs. Patients in control group got Danlou Tablets by oral administration， 5 tablets/time， 3 times/day. Patients in observation group got dispensing decoction pieces of Danshenyin and Wendantang 1 dose/day. The treatment continued for 3 months in both groups. Scores of angina attack were graded every week. Before and after treatment， electrocardiogram treadmill exercise test was made to evaluate myocardial ischemia of coronary heart disease， and scores of phlegm stasis block syndrome and Seattle Angina questionnaire （SAQ） were graded for TCM symptoms and quality of life. Levels of hemorheology index， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， intercellular adhesion molecule-1 （ICAM-1）， Cystatin C （CysC）， homocysteine （Hcy）， ischemic modified albumin （IMA） and macrophage migration inhibitory factor were detected. In addition， safety was evaluated.ResultAfter treatment， scores of times， duration， degree of angina pectoris， nitroglycerin dosage of angina pectoris and nitroglycerin dosage in the observation group were lower than those in the control group （P<0.01）. Total exercise time， duration of ST depression for 1.0 mm， occurrence time of stable angina pectoris， metabolic equivalent and scores of Duke in the observation group were more than those in the control group （P<0.01）. Score of stagnation of phlegm and blood stasis in the observation group was lower than that in the control group （P<0.01）， while score of SAQ was higher than that in the control group （P<0.01）. Levels of IL-6， TNF-α， ICAM-1， CysC， IMA， Hcy， MIF， whole blood viscosity （low cut， high cut）， whole blood reducing viscosity， plasma viscosity， platelet aggregation rate and fibrinogen （FIB） in the observation group were lower than those in the control group （P<0.01）. Effect of angina pectoris in observation group was superior to that in control group （Z=2.091， P<0.01）. No adverse reactions related to Danshenyin combined with Wendantang were found.ConclusionAddition and subtraction therapy of Danshenyin combined with Wendantang based on the routine western medicine treatment can control the attack of angina pectoris， relieve the symptoms of phlegm and stasis block syndrome， and improve the quality of life for patients with SAP， showing superior clinical efficacy and safety. In addition， it can improve the hemorheology of patients， inhibit the inflammatory reaction， reduce the stenosis or obstruction of lumen in order to improve the degree of myocardial ischemia.
Abstract：ObjectiveTo observe the clinical efficacy of Qufeng Juanyin Decoction on bronchial asthma in children （syndrome of wind phlegm blocking lung） during the stage of attack， and the regulatory effect on T helper cell 17 （Th17）/regulatory T cell （Treg） and related factors.MethodOne hundred and thirty patients were randomly divided into observation group （65 cases） and control group （65 cases） by random number table. In control group， 61 cases completed the treatment， including 1 fell off or lost visit， 3 was eliminated because of breach of protocol. And in observation group， 63 patients completed the treatment， including 2 cases fell off or lost visit. Both of the groups got Budesonide suspension by atomizer， 1 mg/time， 2 times/day， and severe children were added with Terbutaline Sulfate Aerosol every morning and evening， 2 sprays/time. Patients in control group got Suhuang Zhike capsules， 2 grains/time， 3 times/day. Patients in observation group got Qufeng Juanyin Decoction， 1 dose/day. The course of treatment lasted for 7 days. Onset and mitigation times of asthma were recorded. And before and after treatment， pulmonary function was evaluated， and daily variation rate of peak expiratory flow （PEF）， first second expiratory flow as a percentage of expected （FEV1%） and ratio of first second forced expiratory volume （FEV1） and forced vital capacity （FVC） were recorded， and scores of syndrome of wind phlegm blocking lung and exhaled nitric oxide were detected. At the first week after the treatment， asthma control test in children （C-ACT） was made. Levels of Th17 cells， Treg cells， interleukin-17 （IL-17）， IL-6， IL-10， IL-22 and IL-35 were also detected. And the safety was evaluated.ResultOnset and mitigation times of asthma in observation group were shorter those in control group （P<0.01）. The daily variation rate of PEF in observation group was lower than that in control group （P<0.01）， while levels of FEV1% and FEV1/FVC were higher than those in control group （P<0.01）. Asthma control in observation group was better than that in control group （Z=2.106， P<0.05）. FeNO and score of syndrome of wind phlegm blocking lung were lower than those in control group （P<0.01）. Levels of Th17， Th17/Treg， IL-17， IL-6 and IL-22 were lower than those in control group （P<0.01）， whereas levels of proportion of Treg cells， IL-10 and IL-35 were higher than those in control group （P<0.01）. The total effective rate in observation group was 96.83% （61/63）， which was better than 85.25% （52/61） in control group （χ2=5.141， P<0.05）. And the total effective rate of traditional Chinese medicine （TCM） syndrome was 98.41% （62/63）， which was better than 86.89% （53/61） in control group （χ2=4.525， P<0.05）. And there was no adverse reaction caused by Qufeng Juanyin Decoction.ConclusionQufeng Juanyin Decoction can shorten the course of disease， improve the lung function， regulate the expressions of Th17/Treg cells and related factors， promote the immune balance of Th17 / Treg， reduce airway inflammation and airway hyperresponsiveness， and effectively control the attack of asthma， with a good clinical efficacy and safety on bronchial asthma in children （syndrome of wind phlegm blocking lung） during the stage of attack.
Keywords：bronchial asthma;children;attack stage;syndrome of wind phlegm blocking lung;Qufeng Juanyin Decoction;airway inflammation;T helper 17 cell;regulatory T cell
Abstract：ObjectiveTo investigate the intervention of Hedyotis diffusa （HDW） on colitis associated cancer （CAC） model mice and explore its mechanism.MethodThe CAC mouse model was established by synergistic action of azoxymethane （AOM） and dextran sulfate sodium （DSS）. The intervention of HDW on CAC mice was evaluated by disease activity index （DAI）， colonic tissue morphology， pathological injury score and tumorigenesis rate. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and multivariate statistical analysis were used to analyze the metabonomics of mice serum and to explore the mechanism of HDW intervention on CAC.ResultHDW could significantly improve the general condition of CAC mice， decrease DAI， colon gross morphological score， histopathological score and tumorigenesis rate. Compared with the normal group， 38 kinds of differential metabolites were screened in the model group， including 11 potential biomarkers， involving 11 main metabolic pathways. HDW could significantly regulate 9 kinds of differential metabolites ［niacinamide， uridine， 4-pyridoxic acid， LysoPC （18∶0）， LysoPE （0∶0/20∶0）， myo-inositol， purine， sphinganine 1-phosphate and tetradecanedioic acid］ in the model group， including 2 kinds of potential biomarkers （myo-inositol and niacinamide）， and HDW could regulate nicotinate and nicotinamide metabolism and inositol phosphate metabolism.ConclusionHDW has a therapeutic effect on CAC， which may be achieved by regulation of energy metabolism and glucose metabolism.
Abstract：ObjectiveTo study the effect of sedimentary type Limonitum on hemostatic indexes in blood and metal ions in serum of rats with hemorrhage.MethodThe hemorrhagic rat models were established by warfarin sodium. The experimental animals were divided into control group，model group，powder group and water decoction group. On day 15 from drug administration， the contents of 6-keto prostaglandin F1α（6-keto-PGF1α），thromboxane B2（TXB2），arachidonic acid（AA），endothelin 1（ET-1），platelet activating factor（PAF），P-selectin（PS），and Ca2+ in the whole blood of rats in each group were determined by enzyme-linked immunosorbent assay（ELISA）. The contents of Na，Mg，K，Ca，Fe，Al，Li，Be，Ti，V，Cr，Mn，Co，Ni，Cu，Zn，As，Sr，Cd，Sn，Sb，Ba，and Pb in serum samples were determined by inductively coupled plasma optical emission spectrometer（ICP-OES） and inductively coupled plasma mass spectrometry（ICP-MS）.ResultCompared with the model group，the content of 6-keto-PGF1α was reduced in the powder group and water decoction group （P<0.05），and the contents of TXB2，AA，ET-1，PAF，PS，Ca2+ weresignificantly increased（P<0.01），with a positive and beneficial regulatory effect. In the powder group， 10 kinds of metal elements in serum of rats were significantly and positively regulated： Na，K，Ca，Fe，Li，Ti，V，Co，Cu，and Zn（P<0.05，P<0.01）. In the water decoction group， 10 metal elements with significant positive regulation were as follows： Na，K，Ca，Fe，Li，V，Ni，Cu，Zn，and Sr（P<0.05，P<0.01）. In addition，the content of Cr（P<0.01） in the powder group and Cr（P<0.01），Pb（P<0.05） in the water decoction group were significantly reduced.ConclusionThe powder and water decoction of sedimentary type Limonitum had definite and positive intervention effect on warfarin hemorrhage model rats，which could play a coagulation role by enhancing the vasoconstriction ability，promoting the activation of platelets，and increasing the platelet aggregation rate and blood viscosity. The metal elements such as Na，K，Ca，Fe，Li，Ti，V，Co，Cu，Zn，Ni and Sr may be the material basis for sedimentary type Limonitum to exert hemostatic effect. According to the above indicators，the intervention effect of powder group and decoction group was basically the same.
Keywords：mineral Chinese medicine（MCM）;Limonitum;hemostatic effects;Warfarin;metal elements;material basis;mechanism of action
Abstract：ObjectiveTo analyze the chemical constituents in Euodiae Fructus by ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS/MS）.MethodThe chromatographic separation was performed on an ACQUITY UPLC BEH C18 column （2.1 mm×100 mm， 1.7 μm） with acetonitrile （A）-0.1% formic acid aqueous solution （B） as mobile phase （0-3 min， 6%A； 3-4 min， 6%-10%A； 4-7 min， 10%-12%A； 7-8 min， 12%-14%A； 8-13 min， 14%-15%A； 13-15 min， 15%-20%A； 15-18 min， 20%-30%A； 18-21 min， 30%-49%A； 21-25 min， 49%-51%A； 25-27 min， 51%-73%A； 27-30 min， 73%-80%A； 30-31 min， 80%-100%A； 31-32 min， 100%A） for gradient elution. The column temperature was 35 ℃， and the flow rate was 0.4 mL·min-1. Mass spectrometry was performed using an electrospray ionization and data were collected in positive and negative ion modes， and the detection range was m/z 100-1 200. The chemical constituents in Euodiae Fructus were identified rapidly and comprehensively based on the accurate relative molecular mass and combined with literature data and reference substances.ResultA total of 92 chemical constituents were speculatively identified from the 70% methanol extract of Euodiae Fructus， including 39 alkaloids， 19 flavonoids， 12 limonoids， 20 phenolic acids and 2 organic acids. Among them， 26 compounds were confirmed by the reference substances.ConclusionThe compound types of Euodiae Fructus are multiple and quite different in polarity. The chemical compositions of Euodiae Fructus from different regions and species are similar. The established method is rapid and accurate， with which the chemical compositions of Euodiae Fructus have been identified comprehensively. Therefore， this study provides an experimental reference for further clarifying active and toxic constituents of Euodiae Fructus.
Abstract：ObjectiveChemical constituents in hypoglycemic effective fractions of Longan Folium were isolated and identified by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） to clarify the hypoglycemic substance basis of Longan Folium.MethodChemical constituents in hypoglycemic effective fractions of Longan Folium were isolated on a Thermo Hypersil GOLD C18 column （2.1 mm×100 mm， 1.9 μm）， the mobile phase was 0.1% formic acid acetonitrile solution and 0.1% formic acid solution （containing and 10 mmol ammonium acetate） for gradient elution. HRMS was operated in the positive and negative ion modes with the scanning range of m/z 100-1 500.ResultThe secondary fragment ion information of target compounds was selected and compared with the compounds reported in the databases and related literature to further confirm these compounds. Nine compounds were identified in the ethanol fraction of Longan Folium， including cynaroside， kaempferol， quercitrin， luteolin， shikimic acid， citric acid， L-tyrosine， adenosine and nicotinamide. A total of 11 compounds were determined in the ethyl acetate fraction （cynaroside， quercitrin， kaempferol， luteolin， shikimic acid， gallic acid， protocatechuic acid， adenosine， nicotinamide， L-phenylalanine and scopoletin）， and 10 compounds were identified in the n-butanol fraction （cynaroside， kaempferol-3-O-rutinoside， kaempferol， astragalin， luteolin， citric acid， gallic acid， adenosine， nicotinamide and 5-hydroxymethylfurfural）. And five common compounds were identified in these three hypoglycemic effective fractions.ConclusionThe established UPLC-Q-Orbitrap HRMS can quickly identify chemical constituents in three hypoglycemic effective fractions of Longan Folium， their main chemical constituents are flavonoids and their glycosides， organic acids and nitrogen-containing compounds， which provides technical support and scientific evidence for the study on pharmacodynamic material basis and quality control of Longan Folium.
Abstract：Tsaoko Fructus is a type of food with the homology of medicine and food，and has a long history of cultivation and application in China. With the deepening of the development and utilization of Tsaoko Fructus，its economic value has appeared obviously，and relevant industries have great potential，with an important role in poverty alleviation in mountainous areas. However，the plants source of Tsaoko Fructus are confused in the process of actual production and resource utilization，and there is a lack of systematic report about the origin of varieties and medicinal history. The paper focused on a textual research for its names，plant sources，changes of the genuine producing areas and traditional efficacy through consulting the herbal works and the analysis of modern literature. The results showed that the medicine of Tsaoko Fructus was first recorded in ancient literatures of the Song dynasty，and there were many aliases and synonyms of the herb， with a great difference between ancient and modern times. In modern records，the medicinal alias names such as Hongcaoguo，Tucaoguo，Caoguoren are similar with the Chinese name of Caoguo，but they are not the same kind of plant and shall be distinguished. In the Ming dynasty，variety and source of the herb was complicated，and it was often recorded as the same class of medicinal materials with Amomi Fructus Rotundus and Alpiniae Katsumadai Semen，until it was listed as a class of medicinal material and distinguished from confounding medicines in the Qing Dynasty. The prescriptions containing Tsaoko Fructus include Caoguoyin，Caoguosan，Caoguowan，Caoguoshushui. Tsaoko Fructus could be used as medicine with peel or only kernel according to different diseases，and mainly processed with water or wine. In addition，there are other processing methods，such as frying，salt-processing， ginger- processing，simmering flour. Ancient literatures have basically the same records on properties，efficacies and indications of Tsaoko Fructus，considering it was warm in nature with the effect in relieving vomiting，eliminating food，intercepting malaria，expelling phlegm. This study provided a theoretical basis for its origin，quality control and resource development and utilization.
Keywords：Tsaoko Fructus;medicinal textual research;product name;origin;change of producing area
Abstract：ObjectiveTo review and summarize the current research status of traditional Chinese medicine（TCM） for the treatment of chronic atrophic gastritis（CAG），provide references and hints for relevant studies，and contribute to the further understanding of TCM and the application of TCM in the treatment of CAG with scientific evidence.MethodThe PubMed and Web of Science databases were searched for relevant literature on the treatment of CAG with TCM from their establishment to August 31，2020. Eligible randomized controlled trials （RCTs） and animal studies were included according to the inclusion and exclusion criteria，and then the information of the included studies was extracted，summarized，and organized for further analysis.ResultA total of 4 RCTs and 21 animal studies （including 13 papers on compound studies，3 papers on single herb studies，and 5 papers on monomer studies） about TCM treatment for CAG were included in this study. RCTs showed that TCM could work well in improving the pathological state of gastric mucosa and clinical symptoms in patients. However，there were problems of low study quality，and non-uniform diagnostic criteria for gastric mucosal pathology and clinical efficiency evaluation. Animal experiments mainly focused on the study of drug mechanism exploration，and their results showed that TCM treatment of CAG was characterized by multi-target action. However，the animal experiments also had some problems such as inconsistence of CAG animal model establishment，positive drug selection，drug intervention methods as well as intervention cycles among different experiments.ConclusionThe efficacy of TCM in the treatment of CAG has gradually gained global recognition，but there is still a need for further standardization and unification of research methods. In the future，high-quality clinical trials and standardized animal experiments are still needed to conduct in-depth studies on the time for intervention，intervention methods，active ingredients and mechanisms of TCM，so as to make contributions to the full understanding and application of TCM in the treatment of CAG.
Keywords：chronic atrophic gastritis;traditional Chinese medicine;randomized controlled trials;animal experiments;research status;literature study
Abstract：ObjectiveTo explore the reasonable combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in treatment of cerebral malaria and investigate its mechanism based on network pharmacology.MethodThe traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and SymMap were used to obtain all the chemical components of Artemisiae Annuae Herba and Chuanxiong Rhizoma and the action targets were screened to construct a component target protein-protein interaction （PPI） network. Target genes related to cerebral malaria were collected with use of GeneCards and DisGeNET databases. Common targets were screened by overlapping drug targets and disease targets， and protein-protein interaction network analysis was performed to get key targets. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out to get main signaling pathways. Furthermore， the classical experimental cerebral malaria mouse model was used to detect survival curve， protozoanemia level， survival rate， experimental cerebral malaria （ECM） coma and behavior scores. RayBio® cytokine antibody array was used to detect the expression level of cytokines in tissues and experiment was conducted for verification.ResultAfter combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma， 23 active ingredients， 179 drug targets， and a total of 100 common targets of the drug and disease were obtained. GO functional analysis identified 59 items （P<0.05）， involving cytokine activity， growth factor activity， immune response， etc. KEGG pathway analysis revealed 51 related signaling pathways. The experimental results showed that the combined use of Artemisiae Annuae Herba and Chuanxiong Rhizoma could significantly improve the clinical signs of ECM mice， such as survival state， coma and behavioral scores. In the detection of expression levels of related cytokines in mice， the expression levels of γ-interferon （IFN-γ）， interleukin-10 （IL-10）， IL-4， and IL-1β in the compatible drug combination drug were significantly higher than those in the model group （P<0.05）， which was consistent with the overlapping core targets predicted by network pharmacology.ConclusionBased on the network pharmacology analysis and in vivo experiment verification， this study confirmed the synergistic effect of the combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in the treatment of cerebral malaria， providing clear direction for further mechanism research， and a new possibility for the clinical intervention of cerebral malaria.
Abstract：For rheumatoid arthritis， glucocorticoids or immunosuppressive agents are currently used in clinical treatment， but long-term use of these drugs has large side effect on humans， and immunosuppressive agents are expensive. To a certain extent， its wide application is limited. The treatment of rheumatoid arthritis with traditional Chinese medicine（TCM） has a long history and little toxic and side effect， but its specific mechanism of action needs further exploration. The process of autophagy is an active biological process in which cells themselves are stimulated by the outside world through intracellular signal transduction to maintain a stable internal environment. Its abnormality is involved in the occurrence of many diseases. At present， studies have shown that abnormal autophagy is closely related to the occurrence and development of rheumatoid arthritis， which can interfere with the pathological changes of RA pannus formation， synovial inflammation and bone destruction and affect the disease process. In recent years， many studies have found that traditional Chinese medicine and its active ingredients can affect the pathological development of rheumatoid arthritis by regulating autophagy. This article investigates the relevant literature on the intervention of rheumatoid arthritis by regulating autophagy through using TCM， with a view to providing new ideas for basic research， new drug development and clinical treatment of rheumatoid arthritis.
Keywords：rheumatoid arthritis;autophagy;synovial arthritis;bone destruction;pannus;traditional Chinese medicine
Abstract：Rheumatoid arthritis （RA） is a common immune-mediated inflammatory autoimmunity disease. Due to its clinical characteristics， RA is classified into the category of "Bi syndrome" in traditional Chinese medicine. Huangqi Guizhi Wuwutang （HGW）， originated from Synopsis of Golden Chamber Jinkui Yaolue， is composed of Astragali Radix， Cinnamomi Ramulus， Paeonial actiflora， Zingiberis Rhizoma Recens， and Jujubae Fructus. It has been used for treatment of blood "Bi syndrome" in clinical practice， and nowadays， it is also widely used for treatment of RA or RA with wind-cold-dampness Bi syndrome or Qi and blood deficiency Bi syndrome. In 2018， HGW was collected in the Catalogue of Ancient Classical Prescriptions （the First Batch）. In order to provide insight for standardized clinical medication and lay a solid foundation for its further development， we herein reviewed literatures of clinical and animal studies on HGW treatment in RA. According to the basic pathogenesis of RA， HGW can be used for treatment of general RA， RA with wind-cold-dampness Bi syndrome or Qi and blood deficiency Bi syndrome alone or in combination with other drugs. The mechanisms of HGW were related to inhibition of inflammatory cytokines expression， inhibition of lipid peroxidation of synovium， and promotion of apoptosis. However， many issues in the current research still needed to be addressed， such as lack of standardization of drug compatibility and dosage， lack of standardization of clinical trial scheme，undefined drug interaction and unclear safety on the combination of Chinese medicine with chemistry drugs， lack of proper syndrome animal model， and limited study about molecular mechanisms. We propose that future research should focus on the standardization of the clinical trial scheme and RA syndrome of HGW， clarify the principle of drug compatibility and dosage， drug interaction and safety. In terms of mechanistic study， the research should focus on animal models of RA syndrome using multiple dimensions such as genetics， transcription， and metabolism.
Abstract：Atherosclerosis is one of the most common diseases that threaten human health. How to effectively inhibit atherosclerosis， extend the survival time and improve the quality of life has become one of the most urgent issues to be solved clinically. Mongolian medicine， with a long history of managing human diseases， is an important part in traditional Chinese medicine （TCM） and has distinct ethnic characteristics. It has been gradually formed and developed by absorbing some theories of Tibetan medicine， Indian medicine and relevant knowledge of TCM. Mongolian medicine has many advantages， including but not limited to， low toxicity and diverse structure. However， the action mechanism of Mongolian medicine in preventing and managing atherosclerosis has yet to be fully clarified， which has been a major obstacle for further promotion and application of Mongolian medicine in clinical settings. In this review， the up-to-date research findings on Mongolian medicine were collected， analyzed and summarized， and the anti-atherogenic action mechanism of Mongolian medicine were reviewed from the aspects of anti-inflammatory， lipid-lowering， anti-oxidative stress， vascular endothelial cell protection， and inhibition of vascular smooth muscle cell proliferation and migration.
Keywords：Mongolian medicine;anti-atherosclerosis;mechanism of action;atherosclerosis;research progress
Abstract：Quality evaluation based on character identification of traditional Chinese medicinal materials is the wisdom crystallization of the long-term medication experience of the pharmacists in the past dynasties， and is a quality evaluation system with the characteristics of traditional Chinese medicine （TCM）. Because of its simple language， easy to understand and easy to operate， it plays an important guiding role in the quality evaluation of TCM. Modern electronic sensory apparatus technology can realize the objective expression of TCM characters. Some scholars correlated their expression results with the contents of the main chemical components in TCM， proving that quality evaluation based on character identification of traditional Chinese medicinal materials has a certain scientific basis. However， the scientific connotation of quality evaluation based on character identification of traditional Chinese medicinal materials has not yet been clearly clarified. There is a lack of systematic research on which characters of TCM can truly reflect its quality. Therefore， the author summarizes quality evaluation based on character identification of traditional Chinese medicinal materials from three aspects. It makes clear that the idea of quality evaluation based on character identification of traditional Chinese medicinal materials is derived from analogical thinking， and combs the four stages of germination， development， prosperity and maturity experienced in its formation process， summarizes the modern research progress of this theory， clarifies that the role of the theory in evaluating the quality of medicinal materials， guiding the classification of commodity specifications， and harvesting and processing of medicinal materials. It is recommended that the follow-up should be strengthened on the research of quality evaluation based on character identification of traditional Chinese medicinal materials， make full use of electronic sensory instruments， liquid-mass spectrometry， biological efficacy evaluation and other technologies， strengthen the objective description of the characteristics of TCM， and attach importance to the analysis of the correlation between the overall characteristics of TCM and its efficacy， and establish a new research model related to the characteristics-active ingredients-pharmaceutical effects of TCM， in order to elucidate the scientific connotation of quality evaluation based on character identification of traditional Chinese medicinal materials， so as to better serve the quality evaluation of TCM.
Keywords：quality evaluation based on character identification of traditional Chinese medicinal materials;analogical thought;historical evolution;character-quality;correlation analysis;application value;electronic sensory apparatus
Abstract：Dendrobium（Orchidaceae） is traditional Chinese medicine with a high healthcare value，which can nourish Yin and tonify deficiency. Eighty-nine flavonoids were isolated from Dendrobium，mainly including flavones，flavanoes and flavonols. Among them，there were 40 flavonoids，the main aglycones were apigenin and chrysoeriol；20 flavanones；and 15 flavonols，and the main aglycones were kaempferol and quercetin. D. officinale and several other species also have flavanonols，anthocyanidins，chalcone and isoflavones. There were 34 species of Dendrobium containing flavonoids，including 38 flavonoids in D. officinale，28 flavonoids in D. huoshanense，19 flavonoids in D. devonianum，12 flavonoids in D. wardianum，5 flavonoids in D. thyrsiflorum，4 flavonoids in D. denneanum and D. findlayanum. Common flavonoids included naringenin，quercetin，rutin，which had pharmacological effects of resisting oxidation，lowering blood sugar，improving blood circulation，lowing cholesterol，and protecting the cardiovascular system. The existing studies of Dendrobium-related species，flavonoids and their physiological functions were reviewed in the expectation to promote the attention of the industry to Dendrobium flavonoids and explore values of Dendrobium plants in efficacy and food fields.
Abstract：Astragali Radix-Angelicae Sinensis Radix （AA） is a basic pair of drugs mainly targeting the syndrome characteristics of Qi and blood diseases. LI Dong-yuan's Danggui Buxuetang （DBT） is composed of AA， which is mainly used to tonify Qi and generate blood， with main indications of Qi deficiency and blood deficiency， blood heat and so on. It is favored by doctors because of its refined prescription and remarkable curative effect. However， there are many compatibility ratios of AA in different prescriptions in ancient books， and their efficacy and indications are also slightly different. This research showed that DBT also had the effect of invigorating Qi and activating blood， and the previous study of the group showed that 3∶1 compatibility ratio of the two herbs in the total amount of 36 g had more obvious effect of invigorating Qi and activating blood. By consulting the relevant literature， it was found that the drug pair had a certain effect of invigorating Qi and activating blood in various compatibility ratios such as 1∶1， 3∶1， 1∶5， 3∶2， 2∶1， 5∶1. The corresponding pharmacological effect mainly included regulating the energy metabolism of substances， regulating immune function， reducing blood viscosity， anti-oxidation stress， anti-inflammation， lowering blood lipids， lowering blood sugar， protecting heart function， protecting blood vessel wall， intervening angiogenesis， fighting against organ tissue fibrosis and so on. Regardless of the AA single-medicine's activating blood effect and the theory that "Qi circulation leads to blood circulation" or the drug pair's manifestation in modern pharmacological effects， all of these have confirmed that AA's effect of invigorating Qi and activating blood does exist， and the difference of action performance caused by different ratios of AA is closely related to dosage and proportion， which needs further study. Based on the study focusing on the effect of tonifying Qi and generating blood， it is easy to ignore the effect of invigorating Qi and activating blood， which limits the clinical application of the latter. Therefore， the tonifying Qi and activating blood circulation effect of the drug pair is reviewed in this paper， so as to provide a theoretical basis for its clinical rational drug use and related research.
Abstract：Xihuangwan is composed of four Chinese medicines： Bovis Calculus， Olibanum， Myrrha， and Moschus. Modern pharmacology studies have shown that Xihuangwan has anti-inflammatory， antibacterial， anti-tumor， anti-mammary gland hyperplasia effect， and can enhance the body's immune function. Cancer seriously endangers public health and safety-of-life， and is a major cause of mortality of Chinese citizens. It is a disease with intricate etiopathogenesis caused by the joint action of circumstances and hereditary factors. At present， anti-tumor chemotherapy drugs in clinical application not only have toxic and side effect， but also affect clinical efficacy and prognosis of patients. Long-term use will also lead to drug resistance of tumors. As a traditional classic anti-cancer prescription， Xihuangwan has been used more and more in tumor research with the rise of Chinese medicine culture. It is provided with remarkable inhibitory effect on liver cancer， gastric cancer， carcinoma of the lungs， mammary gland， colorectal carcinoma and other malignant tumors. In clinical practice， Xihuangwan ， mostly used as adjuvant drugs in combined use with chemotherapy drugs for anti-tumor effect， can reduce the side effect of chemotherapy drugs and the untoward reaction of sufferers， improve the survivability of patients to chemotherapy， reduce or delay postoperative tumor recurrence， enhance the body's immune function， and reverse the tolerance of tumor cells. Based on the anti-tumor research of Xihuangwan， we summarized its mechanisms in inducing cell apoptosis， regulating amino acid metabolism， reversing drug resistance， interfering with cell cycle， resisting tumor metastasis and invasion， regulating immune function， improving tumor microenvironment， and regulating signal pathways， as well as its clinical combination with chemotherapeutic anti-tumor drugs， analyzed the current anti-tumor research status of Xihuangwan's research， and put forward the shortcomings and unresolved problems in order to provide theoretical basis for further research and clinical application of Xihuangwan.
Keywords：Xihuangwan;anti-tumor;mechanism of action;combined use for anti-tumor;research status
Abstract：Citri Reticulatae Semen is a traditional Chinese medicine in our country. By referring to the relevant literature and materials such as the works of ancient and modern materia medica， this paper summarizes the historical evolution of processing， quality analysis， pharmacological effects and other aspects of Citri Reticulatae Semen. The results showed that the processing methods of Citri Reticulatae Semen in the past dynasties mainly included stir-frying， processing with wine， baking with wine， etc. The modern stir-baking with salt solution was developed on the basis of the ancient stir-frying with green salt， most of the national and provincial processing standards contained crude and salt-processed products of Citri Reticulatae Semen. The properties and flavors of Citri Reticulatae Semen in the past dynasties were basically consistent with those in modern times. It is bitter in taste and neutral in nature. It belongs to the liver and kidney meridians and has the effects of regulating Qi， dispersing knots and relieving pain. Citri Reticulatae Semen contains limonins， fatty acids， proteins and mineral elements， etc. High performance liquid chromatography （HPLC）， gas chromatography-mass spectrometry （GC-MS） and thin layer chromatography （TLC） were commonly used to detect and analyze Citri Reticulatae Semen. Citri Reticulatae Semen has anti-tumor， anti-inflammatory， analgesic and antibacterial activities， and processing can change the content of its chemical components to a certain extent. In a word， the current research about Citri Reticulatae Semen is not enough in-depth， it is necessary to further analyze the material basis of efficacy of Citri Reticulatae Semen and its processed products， explore the change law of chemical components before and after processing and the relationship between chemical composition and activity， and clarify the processing mechanism for providing scientific basis for its standardized processing， quality control and clinical rational use.
Abstract：The root of Tripterygium wilfordii has the effect in dispelling wind and eliminating dampness. Now it is mostly used in the treatment of systemic lupus erythematosus and other diseases. Triptonide is a diterpene small molecule compound extracted from T. wilfordii. In the early years， it was studied as a potential drug with anti-inflammatory and anti-reproductive effects. Recently， researchers found that its anti-tumor effect was particularly prominent because triptonide could inhibit the growth of a variety of tumors with different mechanisms at the nanomole dose， with a potential to be used as a broad-spectrum anti-cancer drug. In addition， due to the low yield from T. wilfordii， low bioavailability due to poor water solubility and anti-reproductive side effect as an antitumor drug， it will become study hotspots to exploring its synthesis and preparation and modifying its structure to reduce cost， improve bioavailability and reduce side effect， while maintaining its pharmacological activity. The authors reviewed domestic and foreign studies and patents on triptonide， and summarized its pharmacological activity and mechanism. It is found that although current studies on triptonide are still in the preliminary stage， there have been increasingly more studies on its anti-tumor mechanism year by year since 2014. This paper mainly introduces the antitumor pharmacological activity and mechanism of triptonide. In addition， it reviews anti-inflammatory， immunosuppression and anti-reproductive pharmacological effect of triptonide， as well as the existing studies on its toxicity， synthesis and structural modification. The authors put forward some personal ideas on its future study direction， in the hope to provide thinking and inspirations for other researchers and provide references for further development and research.
Abstract：Hydroxytyrosol as one of natural anti-oxidants，extracted from the fruits and leaves of Olea europaea，is a natural polyphenol compound in the form of esters. Recently，considerable studies showed that hydroxytyrosol demonstrated intrinsic biological activity for metabolic syndromes， cardiovascular- and neurodegenerative-related diseases，and it was revealed to play the roles in the anti-activities of cancerous，inflammatory as well as depressing issues. In addition，hydroxytyrosol is an oleophilic and hydrophilic compound with high bioavailability and low cellular cytotoxicity. It could be absorbed by various tissues and could easily passe through blood brain barrier. Therefore，hydroxytyrosol was introduced as one of the key subjects targeted by innovative drug development. However，it has a short half-life in vivo and non-tissue specific，which lead to its limitation in clinical application， so further in-depth studies are still needed. The authors had a literature review of hydroxytyrosol，and summarized the basic properties of its pharmacokinetic，pharmacological effects and molecular mechanisms. This article mainly focused on it’s pharmacological activity and the mechanism involved in treating damages induced by the oxidative stress，in alleviating cardiovascular diseases and in inhibition of neurodegenerative diseases. In this article， its anti-inflammatory，anti-tumor，anti-depressant effects，other biological activities，and pharmacokinetics were also briefly reviewed. The authors put forward some personal thoughts on its future research direction，hoping to provide ideas and inspirations for the vast number of researchers，and provide references for its further development，research and application.