Exploring the effect of Bushen Bitong recipe-containing serum on IL-1β-induced chondrocyte apoptosis based on SOX9/NF-κB/MMP-13 signaling pathway

Objective:To observe the effect and possible mechanism of action of Bushen Bitong recipe(BSBT)containing serum on IL-1β-induced chondrocyte apoptosis.Methods:Generation 3 rat chondrocytes were randomized into Control,IL-1β,IL-1β+BSBT(L),IL-1β+BSBT(M),and IL-1β+BSBT(H)groups(5%,10%and 15%BSBT-containing serum),and then 24h after intervention respectively,the cell proliferation and Apoptosis rate;Western blot detected the expression levels of Bcl-2,BAX,Caspase-3,SOX9,NF-κB p65,MMP-13 proteins in chondrocytes.ELISA detected the levels of TNF-α,IL-6,and bFGF in the supernatants of chondrocyte culture.Results:Compared with Control group,cell proliferation activity decreased,apoptosis rate increased,NF-κB p65,MMP-13 protein level and TNF-α,IL-6 level increased,and SOX9 protein level and bFGF level decreased in IL-1βgroup;compared with IL-1βgroup,different concentrations of BSBT-containing serum group,cell proliferation activity increased,and apoptosis rate decreased.NF-κB p65,MMP-13 protein level and TNF-α,IL-6 level decreased,SOX9 protein level and bFGF level increased;compared with IL-1β+BSBT(L)group,cell proliferation activity increased,apoptosis rate decreased in IL-1β+BSBT(M)and IL-1β+BSBT(H)groups,and NF-κB p65,MMP-13 protein level and TNF-αlevel decreased.13 protein levels and TNF-αand IL-6 levels decreased,and SOX9 protein levels and bFGF levels increased.Conclusion:BSBT-containing serum may promote IL-1β-induced proliferation of chondrocytes,reduce apoptosis,improve the microenvironment of chondrocytes,and promote cartilage repair through the SOX9/NF-κB/MMP-13 signaling pathway.

Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome

BACKGROUND Chronic heart failure is a complex clinical syndrome.The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure;however,the underlying molecular mechanism is still not clear.AIM To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure.METHODS The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target genes of chronic heart failure were searched in the Genecards database.The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drugdisease targets,which were then used to construct a key chemical componenttarget network using Cytoscape 3.7.2 software.The protein-protein interaction network was constructed using the String database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database.Finally,our previously published relevant articles were searched to verify the results obtained via network pharmacology.RESULTS A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified,of which quercetin,kaempferol,7-methoxy-2-methyl isoflavone,formononetin,and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3,MAPK3,AKT1,JUN,MAPK1,TP53,TNF,HSP90AA1,p65,MAPK8,MAPK14,IL6,EGFR,EDN1,FOS,and other proteins.The pathways identified by KEGG enrichment analysis include pathways in cancer,IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,calcium signaling pathway,cAMP signaling pathway,NF-kappaB signaling pathway,AMPK signaling pathway,etc.Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α,IL-6,MAPK,cAMP,and AMPK pathways to affect the mitochondrial structure of myocardial cells,oxidative stress,and energy metabolism,thus achieving the therapeutic effects on chronic heart failure.CONCLUSION The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes,oxidative stress,energy metabolism,and other processes.Future studies are warranted to investigate the role of the IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

A Meta-analysis on the Treatment of Insulin Resistance in Polycystic Ovary Syndrome by Bushen Huatan Recipe

Objective:To systematically evaluate the efficacy and safety of Bushen Huatan recipe compared with metformin in the treatment of insulin resistance in polycystic ovary syndrome(PCOS).Methods Researches were reviewed by searching the China National Knowledge Infrastructure(CNKI),VIP network,WanFang database,SinoMed,Cochrane Library,Web of Science,PubMed and Embase up to December 8,2019.We retrieved the RCTs of Bushen Huatan recipe and metformin in the treatment of insulin resistance in polycystic ovary syndrome and applied Revman5.3 software for meta analysis.Results A total of 5 RCTs were included,with a total of 285 PCOS patients.The results showed:①There was no significant difference between the two groups in LH[WMD=-2.68,95%CI(-6.21,0.84),P=0.14]、FSH(WMD=0.36,95%CI(-0.59,1.32),P=0.45]、LH/FSH(WMD=-0.29,95%CI(-1.06,0.48),P=0.46)、fasting blood glucose(FPG)[WMD=0.05,95%CI(-0.18,0.28),P=0.67]、fasting insulin(FINS)[WMD=-0.91,95%CI(-15.28,13.46),P=0.9].②TCM syndrome score:Bushen Huatan recipe group[WMD=-3.10,95%CI(-5.39,-0.81),P=0.008]was better than metformin group;③Total clinical effective rate:Bushen Huatan recipe group[RR=1.50,95%CI(1.18,1.92),P=0.001]was better than metformin group.Conclusion Bushen Huatan recipe has the same effect as metformin in improving the sex hormones and glucose metabolism of patients with PCOS complicated with insulin resistance,and can effectively improve the clinical symptoms of patients,reduce TCM syndrome score,and improve the total therapeutic efficiency.

Efficacy of Jianpi Bushen Huatan Recipe in the treatment of obese polycystic ovarian syndrome:A meta-analysis

Objective:To evaluate the effects of Jianpi Bushen Huatan Recipe on sex hormone levels、blood lipid and blood glucose levels in the treatment of obese poly-cystic ovarian syndrome(PCOS).Methods:Data bases including the CNKI、Vip、Wanfang were searched.Studies about randomized controlled trials(RCT)of the effectiveness of Jianpi Bushen Huatan Recipe Combined with Metformin in the Treatment of obese PCOS were included.Rev Man 5.3 software was used for meta analysis.Results:A total of 11 studies were enrolled.Meta-analysis showed that Jianpi Bushen Huatan Recipe Combined with Metformin significantly improved the clinical total effective rate of patien ts(RR=1.32,95%CI(1.20,1.45),P<0.00001);reduced the body mass index(BMI)(SMD=-0.92,95%CI(-1.13,-0.72),P<0.00001),luteinizing hormone(LH)(SMD=-1.00,95%CI(-1.37,-0.62),P<0.00001),LH/FSH(SMD=-1.03,95%CI(-1.34,-0.71),P<0.00001),insulin resistant index(HOMA-IR)(SMD=-0.59,95%CI(-0.79,-0.40),P<0.00001),fasting insulin(FIN)(SMD=-0.77,95%CI(-1.19,-0.35),P=0.0003),total cholesterol(TC)(SMD=-0.63,95%CI(-0.88,-0.38),P<0.00001),triglycerides(TG)(SMD=-0.60,95%CI(-0.83,-0.36),P<0.00001),highdensity lipoprotein(HDL)(SMD=-0.41,95%CI(-0.51,-0.32),P<0.00001).However,there was no statistically significant in waist-to-hip ratio(WHR),follicle stimulating hormone(FSH),fasting blood sugar(FBS)and low density lipoprotein(LDL).Conclusions:Jianpi Bushen Huatan Recipe Combined with Metformin in the treatment of obese PCOS has an advantage in improving the sex hormone level,blood lipid and blood glucose level,and is superior to metformin alone.

Antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” and chemotherapy on transplanted animal hepatocarcinoma

AIM： To investigate the antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” （recipe for invigorating the kidney, removing blood stasis and toxic substances） and chemotherapy on mice hepatocarcinoma. METHODS： Bushen huayu jiedu recipe （BSHYJDR） consisting of Chinese Cassia Bark, Psoralea, Zedoary, Rhubarb, etc. is equal to 1.5 g/mL liquid of originated herbs after being decoded, filtered, and concentrated. Kunming mice, weighing 18-22 g, were injected with 0.2 mL ascitic hepatocarcinoma H22 containing 1 × 10^7 cells/mL into armpit of the right forelimb of mice. After 24 h, the mice were weighed and randomly divided into tumor-bearing model control group, cisplatin （DDP） group, BSHYJDR high dosage group, low dosage BSHYJDR group, DDP combined with high and low dosage BSHYJDR group, 10 mice in each group. DDP group received injection intraperitoneally （ip） at the dosage of 1 mg/kg （equal to 1/10 LD50）, once a day for 4 d. High and low dosage BSHYJDR groups received intragastric BSHYJDR at the dosages of 26.6 and 13.3 g/kg （20 and 10 times each of clinical adult dosage） respectively, while tumor-bearing model group received the equal volume of distilled water once a day for 10 d. On the 11^th d, the mice were weighed and killed, then the tumor was dissected and weighed, the repression rate （RR） was calculated according to the mean weight of tumor （MWT）. RESULTS： Compared to the model group （MWT： 1.30±0.73）, DDP group （MWT： 0.41±0.09, RR： 68.46%） had a significant difference in the inhibition of hepatocarcinoma H22 （P〈0.01）. High dosage BSHYJDR group （MWT： 0.69±0.29, RR： 46.92%） also had a significant difference in inhibition （P〈0.05）, while no difference was found in low dosage BSHYJDR group （MVVT： 0.85±0.34, RR： 34.62%） （P〉0.05）. When DDP was combined with high dosage BSHYJDR （MWT： 0.29±0.17, RR： 77.69%） and low dosage BSHYJDR （MWT： 0.38±0.21, RR： 70.77%） respectively, we could see improvement of the inhibition effect of DDP on transplanted hepatocarcinoma H22. DDP combined with high dosage BSHYJDR had a significant difference （P〈0.001） compared to DDP, while DDP combined with low dosage BSHYJDR only had a little improvement that is not remarkable. CONCLUSION： Chinese medicine BSHYJDR in combination with chemotherapy can inhibit transplanted hepatocarcinorna in mice.

Effect of Bushen Yiqi Huoxue Recipe on Placental Vasculature in Pregnant Rats with Fetal Growth Restriction Induced by Passive Smoking

Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation （D 15, D 18 and D21）. The rats were randomly assigned into 3 groups： normal group, model group [fetal growth restriction （FGR） model], and Bushen Tqi Huoxue （BYHR） recipe treatment group （BYHR group, the pregnant rats with FGR were treated with BYHR recipe）. Morphological analysis indicated that during initial villous formation, fetal nucle- ated erythrocytes （FNEs） appeared in maternal blood sinus （MBS）. Subsequently, FNEs were sur- rounded by endothelial cells to form fetal capillary （FC） and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining （EIS） in normal and BYHR groups. Whereas, villous formation was suppressed, normal in- crease in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flkl mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while de- creased on D21 in model group as compared with normal group and BYHR group. Immunohistochemi- cally, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D 15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.

Effect of Bushen Yiqi Hexue Recipe (补肾益气和血方) on Pinopodes Expression on Endometrial Surface in Embryo Implantation Dysfunctional Mice

Objective: To explore the therapeutic mechanism of Bushen Yiqi Hexue recipe (补肾益气血方, BYHR), and observe its effect on pinopodes expression on endometrial surface in mifepristone induced embryo implantation dysfunctional mice. Methods: Pregnant Kunming mice were randomly divided into the normal group, the control group and the treated group. Mice in the treated group were administered with BYHR, and those in the normal group and the control group were administered with normal saline, starting from the very first day of pregnancy (Pd1). On the Pd4, mifepristone (RU486) was subcutaneously injected into mice in the control group and the treated group. Pinopodes expression on endometrial surface at 09:30-10:00 pm on Pd4 (regarded as time point 1, T1) and at 09:30-10:00 am on Pd5 (as time point 2, T2) was determined by scanning electron microscopy. Pregnancy rate and average implanted embryos were observed on Pd7. Results: Pregnancy rate and average implanted embryos in the control group were obviously lower than those in the normal group (all P<0.01), while the two parameters were significantly higher in the treated group (P<0.05, P<0.01, respectively) than those in the control group. In the normal group, abundant developing pinopodes were distributed over the whole endometrial surface in T1, and they were altered to a great deal of fully developed pinopodes in T2. But in the control group, only a few pinopodes were expressed locally on endometrial surface in T1, showing a nonsynchronous figure of development, and they completely disappeared in T2. In the treated group, a lot of developing pinopodes were expressed like those in the normal group but somewhat lagged behind, whereas many fully developed pinopodes were expressed in T2. Conclusion: The decrease of the pinopodes in T1 and the cleaning up of them in T2 is possibly the partial mechanism of mifepristone in inducing embryo implantation dysfunction. It is indicated that BYHR could improve pinopodes expression on endometrial surface, eventually better the uterine receptivity and improve the embryo implantation.

Clinical efficacy of angina pectoris after pci in patients with coronary heart disease complicated with type 2 diabetes by Yiqi Yangyin and Huatan Tongluo recipe

Objective:To evaluate the clinical efficacy of Yiqi Yangyin and Huatan Tongluo Recipe in improving the symptoms of angina pectoris and cardiac function in patients with coronary heart disease complicated with type 2 diabetes after PCI.Methods Sixty-two patients with coronary heart disease complicated with type 2 diabetes after PCI were randomly divided into treatment group and control group,with 31 patients in each group.Both groups were treated with western medicine.The treatment group added Yiqi Yangyin and Huayu Tongluo Recipe granules.The changes of metabolic equivalent(METs),angina symptoms,TCM symptoms,BNP,hypersensitive C-reactive protein(hs-CRP),Interleukin-6(IL-6),Tumor necrosis factor-(TNF-α)and left ventricular ejection fraction(LVEF)were analyzed after 1 course of treatment and Corrected TIMI Frame Count(CTFC)after six month.Results The improvement of METS and LVEF in the treatment group was better than that in the control group(P<0.05);the improvement of BNP,hs-CRP,IL-6,TNF-αand CTFC in the treatment group was better than that in the control group;the curative effect of angina pectoris in the treatment group was better than that in the control group;the effective rate of TCM syndrome improvement in the treatment group was better than that in the control group.Conclusion Yiqi Yangyin and Huatan Tongluo Recipe can effectively alleviate angina pectoris symptoms in patients with coronary heart disease complicated with type 2 diabetes after PCI,suggesting cardiac function,inhibiting inflammatory response,and improving microcirculation disturbance.

Jianpi Bushen Recipe affects epithelial-mesenchymal transition in hepatocellular carcinoma through TGF-β and Twist

Backgroud:To explore the effects of Jianpi Bushen Recipe on the epithelial-mesenchymal transition(EMT)of nude mice with transplanted human liver cancer SK-HEP-1 cells.Methods:To establish models with transplanted liver cancer cells,nude mice were divided randomly into three groups:blank group,traditional Chinese medicine(TCM)group and control group.They were given normal saline,Jianpi Bushen Recipe and solafeni through administration by gavage for four weeks.The expression of TGF-β and twist mRNA were detected by real-time PCR.The expression of E-cadherin was detected by Western blot.Results:Compared with the blank group,the expression of transforming growth factor-P(TGF-β)mRNA and twist mRNA in the TCM group and the control group decreased significantly(P<0.05).There was no significant difference between the two groups(P>0.05).The expression of E-cadherin protein in TCM group and control group increased significantly(P<0.01).There was no significant difference between the two groups(P>0.05).Conclusion:Jianpi Bushen Recipe can inhibit the EMT of liver cancer SK-HEP-1 cells in vivo by down-regulating the expression of TGF-β/twist signaling and indirectly up-regulating E-cadherin expression in transplanted liver cancer tissue,indicating the potential of Jianpi Bushen Recipe to inhibit invasion and metastasis of liver cancer.

A meta-analysis on the improvement of endometrial receptivity of PCOS by Bushen recipe combined with Clomiphene

Objective: To systematically evaluate the efficacy and safety of Bushen Recipe combined with clomiphene compared with clomiphene in improving endometrial receptivity of polycystic ovary syndrome. Methods: The time limit is from the establishment of the database to January 2, 2020. A randomized controlled trial was conducted to compare the effects of Bushen Recipe combined with clomiphene and clomiphene on the endometrial receptivity of polycystic ovary syndrome (PCOS). Meta analysis was performed with RevMan5.3 software. Results: A total of 13 RCTS were included, with a total of 797 PCOS patients. The results of this meta-analysis show: there were statistically significant differences in the improvement of endometrial thickness [WMD=1.62,95%CI(1.22, 2.01), P <0.00001], endometrial type[RR=1.51,95%CI(1.28, 1.78), P <0.00001], uterine artery pulse index(PI) [WMD=-0.18,95%CI(-0.27, -0.09) , P <0.0001], uterine artery resistance index(RI)[WMD=-0.08,95%CI(-0.11, -0.05) , P <0.00001], pregnancy rate [RR=2.18,95%CI(1.55, 3.05), P <0.00001], TCM syndrome score[WMD=-6.97,95%CI(-8.97, -4.97) , P <0.00001], effective rate [RR=1.25, 95%CI (1.13, 1.37), P < 0.00001]. Conclusion: Compared with clomiphene alone, Bushen Recipe combined with clomiphene can effectively increase the thickness of endometrium and improve the type of endometrium, promote the blood perfusion of endometrium, improve the pregnancy rate, improve the clinical symptoms, reduce the TCM syndrome score, improve the total efficiency of treatment, with high clinical application value.

Effect of Jiangtang Bushen Recipe (降糖补肾方) in Intervention Treatment of Patients with Impaired Glucose Tolerance

Objective:To evaluate the intervention effect of diet, exercise and Jiangtang Bushen Recipe (JBR, 降糖补肾方), a Chinese herbal recipe, in preventing the progress of patients with impaired glucose tolerance ( IGT ) to diabetes mellitus (DM) type 2. Methods: Fifty-one IGT patients with their diagnosis conformed to the diagnosis standard of WHO, 1999, were randomly divided into the control group (n = 26) and the TCM group (n=25). Patients in the control group attended to the educational course for DM and received dietotherapy and kinetotherapy, and to those in the TCM group, under these treatments, JBR was given additionally. Oral glucose tolerance test (OGTT), body weight index (BWI), levels of blood lipids and fasting insulin of all the patients were examined after 3 months, 6 months and 12 months of treatment. The total observation time was 1 year. Results:Except the 6 cases out of the 51 patients (11.7%), on whom the observa-tion discontinued, in the control group, as compared with before treatment, levels of fasting insulin and fasting blood glucose after treatment were not changed significantly ( P > 0. 05 ) , also insignificant difference was shown in levels of total cholesterol (TC) and triglyceride (TG), thoughthe two indexes lowered slightly after treatment (P>0. 05), but significant difference was shown in comparison of OGTT/2h, blood glucose and BWI (P<0. 05). While in the TCM group, fasting blood glucose was changed insignificantly (P> 0. 05) , but there was significant difference in comparison of fasting insulin, TC, BWI, OGTT/2h and plasma glucose levels (P<0. 01) respectively before and after treatment. At the end of the stud-y, the cumulative cases with conversion to diabetes were 3 (13. 6%) in the control group, and 1 (4. 3%) in the TCM group, x2 test showed insignificant difference in comparison of diabetes conversion rate between the two groups (P>0. 05), however, the TCM group showed a better year conversion rate of normal glucose tolerance than that in the control group (x2 = 8. 31, P<0. 01). Conclusion: TCM intervention is possibly effective in delaying the conversion of IGT to DM type 2, and plays integrative effeciency in impelling IGT patients to health. The favorable education and treatment of DM controlling, including dieto- and kineto-therapy may also be advantageous in IGT intervention, but could not be effective in blocking the advance of IGT.Original article on CJITWM (Chin) 2004 ;24 (4): 317

Effect of bushen tiaopi recipe on sex hormones, immune function and oxidative stress in patients with climacteric syndrome

Objective: To explore the effect of Bushen Tiaopi Recipe on sex hormones, immune function and oxidative stress in patients with climacteric syndrome and guide clinical medication. Methods: A total of 140 cases of climacteric syndrome patients who were treated in our hospital from May 2016 to May 2017 were selected according to the lottery method, 70 cases in each group. Control group was given Li Fumin treatment, and the observation group was given Li Fumin combined with Bushen Tiaopi Recipe. The levels of sex hormones, T lymphocyte subsets, leptin, adiponectin and oxidative stress were measured before and after treatment in both groups. Result: There was no significant difference in the levels of sex hormones, T lymphocyte subsets, leptin, adiponectin and oxidative stress before treatment between the two groups. After 12 weeks of drug treatment, the level of sex hormone P increased and the levels of LH and FSH decreased in both groups. And the research group P was (21.89±2.29) nmol/L higher than the control group, and the LH and FSH were (4.28±0.43) IU/L and (4.91±0.50) IU/L were lower than the control group. The LP level was decreased and the APN level increased in both groups. Moreover LP level in the research group was (15.34±1.52) μg/L lower than that in the control group, and the APN level was (8.39±0.84) mg/L higher than that in the control group. The SOD level was increased and MDA level decreased in both groups. And SOD level in the research group was (33.27±3.29) U/L, which was higher than that in the control group, and the MDA level was (12.47±1.25) nmol/mL, which was lower than that in the control group. CD4+and CD4+/CD8+levels were significantly elevated in both groups, and CD8+levels were significantly decreased. In the research group, CD4+and CD4+/CD8+were (28.87±2.69)% and (1.41±0.14), respectively, higher than the control group, and the number of CD8+cells was (21.05±2.23)% lower than the control group. Conclusion:Bushen Tiaopi can significantly improve sex hormone levels in climacteric syndrome patients, improve immune function, relieve oxidative stress, and improve treatment effects.

Effect of Combination of Bushen Jianpi Recipe (补肾健脾方) and Erythropoietin on Serum Tumor Necrosis Factor a in Patients with Anemia

Objective: To study the effect of treatment of renal anemia by combination of Bushen Jianpi Recipe (补贤健脾方, BJR, a Chinese experienced recipe for supplementing Shen and supporting Pi) and low dosage erythropoietin (EPO), and the influence of treatment on change of serum tumor necrosis factor α (TNF-α) so as to explore the possible mechanism of integrative Chinese and Western medicine (ICWM) in treating renal anemia. Methods: Patients with renal anemia were randomly divided into two groups, the ICWM group and the control group, supporting treatment such as dialysis, supplementing of ferrous, foliac acid and vitamin B12, was given to both groups. Additionally, to the ICWM group, 50 IU/kg of EPO subcutaneous injection for twice every week, and oral intake of BJR, one dose per day taken in two parts, were given, and to the control group, EPO alone, 50IU/kg by subcutaneous injecting, 3 times perweek, was given. The therapeutic course for two groups was 3 months. Blood levels of hemoglobin (Hb), hematocrit (Hct), TNF-α were measured before treatment and the therapeutic effect was observed. Results: After treatment, the levels of Hb and Hct increased significantly in both groups (P<0. 01) , comparison between the two groups in Hb and Hct after treatment for 3 months showed significant difference (P<0. 05). The serum level of TNF-α was markedly higher than normal range in both groups before treatment, it significantly lowered after treatment in the ICWM group (P< 0.05), but unchanged in the control group. Conclusion: Combination of BJR and EPO could significantly inhibit the production of TNF-α, this may be an important factor for ICWM in effectively improving sensitivity to EPO.Original article on CJITWM (Chin) 2004;24 (2): 106

Effective ingredients, potential targets and mechanism in cancers treatment of Bushen Jiedu Sanjie recipe

Objective: To analyze the active compounds, potential drug targets and corresponding therapy cancer of Bushen Jiedu Sanjie Recipe (BSJDSJR) based on network pharmacology and bioinformatics technology. Methods: The network databases including Cancer HSP, TCMSP, TCMID, TCM-PTD, TCM Database@Taiwan and DrugBank were applied to screen the active compounds, potential drug targets and corresponding cancers of BSJDSJR. Cytoscape3.3 software was used to construct the network between active compounds of Chinese medicine and the corresponding targets. Then, the enrichment of biological processes and KEGG pathways of BSJDSJR were analyzed using DAVID database. Results: According to Oral bioavailability (OB)≥30% and drug like index (DL)≥0.18, 129 active compounds in BSJDSJR were screened out and they targeted to 301 proteins. These targets were closely associated with the occurrence of various cancers, such as bladder cancer, pancreatic cancer, non-small cell lung cancer and colorectal cancer. Further investigation showed that, there were lots of active compounds in BSJDSJR are closely connected with the COX-2/β-catenin signaling pathway, STAT3 signaling pathway and MAPK/ERK signaling pathway. Conclusions: Based on the network pharmacology, the study disclosed the active chemical compounds, potential targets and possible action cancers of BSJDSJR.

醒脑开窍针刺法合并补肾化痰活血方治疗急性脑梗死风痰瘀阻证的临床研究

目的:探究醒脑开窍针刺法合并补肾化痰活血方治疗急性脑梗死风痰瘀阻证的临床效果。方法:选择北京中医药大学孙思邈医院2021年1月-2023年12月收治的急性脑梗死风痰瘀阻证患者106例,采用随机数字表法分为针刺组和联合组,每组53例。两组均给予抗凝、改善微循环、控制血压、神经保护、吸氧、心脏监测等常规西医治疗,针刺组给予醒脑开窍针刺法治疗,联合组在针刺组基础上给予补肾化痰活血方口服治疗。观察两组患者的中医证候积分、神经功能指标、血流动力学指标、神经功能与运动功能及日常生活能力评分、临床疗效、不良反应发生情况。结果:治疗后,两组中医证候积分、美国国立卫生研究院卒中量表(NIHSS)评分、神经胶质纤维酸性蛋白(GFAP)、神经元特异性烯醇化酶(NSE)、中枢神经特异蛋白(S100β)、血流峰值时间(TTP)与阻力指数(RI)水平均较治疗前降低(P<0.05),且联合组低于针刺组(P<0.01);治疗后,两组血清神经生长因子(NGF)、脑血容量(CBV)、平均血流量(Qmean)水平、简式Fugl-Meyer评分(FMA)与Barthel指数(BI)评分均较治疗前升高(P<0.05),且联合组高于针刺组(P<0.01);联合组治疗总有效率高于针刺组(P<0.05);两组不良反应总发生率差异无统计学意义(P>0.05)。结论:醒脑开窍针刺法合并补肾化痰活血方治疗急性脑梗死风痰瘀阻证可降低中医证候积分,缓解临床症状,增加脑血流量,改善神经功能,提高临床疗效,且安全性较高。

补肾化痰汤对多囊卵巢综合征不孕患者卵巢功能及性激素水平的影响

目的观察补肾化痰汤对多囊卵巢综合征(PCOS)不孕患者卵巢功能及性激素水平的影响。方法本研究为随机对照试验。选取陕西省中医医院2023年9月至2024年6月收治的PCOS不孕患者114例,按随机数字表法分研究组与对照组各57例。研究组年龄(27.91±3.15)岁;体重指数(BMI)(25.47±2.59)kg/m^(2);不孕时间(3.57±0.62)年;初潮年龄(13.86±1.15)岁。对照组年龄(28.14±3.25)岁;BMI(25.88±2.64)kg/m^(2);不孕时间(3.45±0.71)年;初潮年龄(14.03±1.06)岁。对照组口服氯米芬,50 mg/次,1次/d,月经周期第5天开始服用,连服5 d。研究组加用补肾化痰汤(200 ml药汁分早晚两次服下,每日一剂),月经结束后第1天连续服用至下次月经。两组均连续治疗3个月经周期。治疗后评估两组疗效;治疗前后,比较两组中医证候积分、卵巢功能[卵巢体积、卵泡数量、抗米勒管激素(AMH)、子宫内膜厚度]、性激素[促黄体生成素(LH)、睾酮(T)、雌二醇(E2)、促卵泡生成素(FSH)];统计两组不良反应发生情况。采用t检验、χ^(2)检验进行统计学分析。结果研究组总有效率高于对照组[91.23%(52/57)比75.44%(43/57)](P<0.05)。治疗后,两组各项中医证候积分均下降,且研究组低于对照组(均P<0.05)。治疗后,两组卵巢体积、卵泡个数、AMH均下降,且研究组[(10.53±2.46)cm^(3)、(6.71±0.95)个、(7.13±2.08)μg/L]低于对照组[(13.94±3.02)cm^(3)、(9.03±1.02)个、(9.05±4.33)μg/L];两组子宫内膜厚度均上升,且研究组[(9.83±0.64)mm]高于对照组[(9.05±0.62)mm](均P<0.05)。治疗后,两组LH、T均下降,且研究组[(6.24±1.79)mIU/ml、(1.42±0.29)nmol/L]低于对照组[(9.05±2.16)mIU/ml、(1.93±0.34)nmol/L];E2均上升,且研究组[(182.16±15.98)ng/L]高于对照组[(166.72±14.03)ng/L](均P<0.05);两组FSH无显著变化(均P>0.05)。两组不良反应总发生率差异无统计学意义(P>0.05)。结论补肾化痰汤对PCOS不孕患者疗效较佳,可有效减轻患者症状,改善卵巢功能及性激素紊乱,且安全性较高。

基于Akt/mTOR信号通路探讨补肾活血方对去卵巢大鼠软骨细胞自噬的影响

目的:研究补肾活血方是否可以通过调控Akt/mTOR信号通路促进去卵巢大鼠软骨细胞自噬反应来保护关节软骨。方法:选取30只SPF级12周龄雌性SD大鼠,体重(247.0±7.0)g,先随机选择6只为空白对照组,剩余大鼠采用卵巢切除术结合右膝关节腔注射碘乙酸钠(monosodium iodoacetate,MIA)建立绝经后膝骨关节炎模型,随机分为模型组、BSHXR-L组、BSHXR-M组、BSHXR-H组,每组6只。运用肉眼观察评分、番红O-固绿染色、免疫组化等方法明确补肾活血方对大鼠关节软骨损伤的保护作用,Western-blot检测自噬相关蛋白的表达,qPCR检测Akt、mTOR及下游自噬基因的相对表达。结果:造模后BSHXR(L、M、H)各组均可减轻软骨组织形态学损伤,免疫组化示Collagen-Ⅱ、Aggrecan表达逐渐升高,基质金属蛋白酶-13(matrix metallopriteinase-13,MMP-13)表达逐渐降低,其中BSHXR-M组和BSHXR-H组与模型组相比差异均有统计学意义(P<0.05)。Western-blot结果示BSHXR(L、M、H)各组自噬通路蛋白p-Akt/Akt、p-mTOR/mTOR受到抑制,下游蛋白Beclin-1、LC3Ⅱ表达逐渐升高,而p62逐渐降低,呈剂量效应。qPCR结果示BSHXR(L、M、H)各组均可促进Beclin-1、LC3ⅡmRNA的相对表达,抑制p62、Akt、mTOR mRNA的相对表达,与模型组相比差异有统计学意义(P<0.05)。结论:补肾活血方可以通过抑制Akt/mTOR信号通路增强软骨细胞自噬反应,进而发挥保护软骨的作用。

补肾固胎方联合黄体酮注射液治疗肾虚型早期先兆流产疗效及对妊娠激素水平和Th1/Th2细胞因子的影响

目的 观察补肾固胎方联合黄体酮注射液治疗肾虚型早期先兆流产疗效及对妊娠激素水平和Th1/Th2细胞因子的影响。方法 采用随机数字表法将符合入选标准的120例肾虚型早期先兆流产患者分为观察组和对照组。对照组予黄体酮注射液治疗,观察组同联合补肾固胎方治疗。连续治疗2周后,比较两组中医证候积分(妊娠期阴道流血、小腹坠胀或疼痛、腰酸痛、膝关节酸软)、妊娠激素水平[雌二醇(Estradiol, E_(2))、人绒毛膜促性腺激素(Human chorionic gonadotropin, β-HCG)、孕酮(Progesterone, P)]、Th1/Th2细胞因子[白细胞介素2(interleukin-2,IL-2)、白细胞介素4(interleukin-4,IL-4)、γ干扰素(Interferon-γ,INF-γ)]改善情况,统计两组治疗总有效率、妊娠结局及不良反应发生率。结果 两组治疗后妊娠期阴道流血、小腹坠胀或疼痛、腰酸痛、膝关节酸软积分,IL-2、INF-γ水平均低于治疗前(P<0.05),且观察组治疗后以上中医证候积分和IL-2、INF-γ水平均低于对照组(P<0.05);两组治疗后IL-4水平均高于治疗前(P<0.05),且观察组治疗后IL-4水平高于对照组(P<0.05);观察组总有效率为(91.7%,55/60),高于对照组(75.0%,45/60)(P<0.05);观察组足月分娩率为(85.0%,51/60),高于对照组(56.7%,34/60)(P<0.05);观察组不良反应发生率为3.3%,低于对照组(25.0%)(P<0.05)。结论 补肾固胎方联合黄体酮注射液能够有效调节肾虚型早期先兆流产患者妊娠激素水平和Th1/Th2细胞因子水平,纠正免疫功能紊乱,降低患者流产率,提高足月妊娠率,改善妊娠结局。

补肾降浊方在糖尿病肾病中的作用及其机制研究

目的 探究补肾降浊方在糖尿病肾病中的作用及其机制研究。方法 复制糖尿病肾病大鼠模型,使用11.04 g/(kg·d)补肾降浊方治疗。根据不同方法将大鼠随机分为Control组、DN组、DN+补肾降浊方组,每组6只。通过生化分析仪测定尿样中的尿白蛋白水平、血尿素氮和血肌酐含量,HE染色检测肾组织病理损伤,Masson染色检测肾组织纤维化情况,实时荧光定量聚合酶链反应检测SIRT1 mRNA,Western blotting检测MAPK/NF-κB信号通路相关蛋白的表达。结果 DN组血尿素氮、血清肌酐、尿白蛋白水平较Control组升高(P <0.05),补肾降浊方组较DN组降低(P <0.05)。DN组SIRT1 mRNA相对表达量较Control组降低(P <0.05),DN+补肾降浊方组较DN组升高(P <0.05)。Control组肾小球和肾小管形态完整,而DN组肾小管基底膜增厚,肾小球肥大,表明DN组大鼠肾功能受到严重损害。与DN组比较,DN+补肾降浊方组大鼠肾小管基底膜增厚和肾小球肥大情况明显减少。与Control组比较,DN组肾小球和肾小管腔中胶原蛋白的沉积量明显增加。与DN组比较,DN+补肾降浊方组大鼠肾小球和肾小管腔中胶原蛋白的沉积量明显减少。DN组SIRT1蛋白较Control组降低(P <0.05),p-p38/p38、p-NF-κB p65/NF-κB p65较Control组升高(P <0.05);DN+补肾降浊方组SIRT1蛋白较DN组升高(P <0.05),pp38/p38、p-NF-κB p65/NF-κB p65较DN组降低(P <0.05)。结论 补肾降浊方促进SIRT1的表达,抑制MAPK/NF-κB信号通路,改善糖尿病肾病肾组织损伤。

补肾活血方治疗肾虚血瘀型卵巢储备功能下降患者的临床疗效观察

目的观察补肾活血方对肾虚血瘀型卵巢储备功能下降(DOR)患者的治疗效果。方法选取北京妇产医院中医科2021年1月至2022年12月就诊的180例诊断为DOR的肾虚血瘀型患者作为研究对象,采用计算机随机分组法分为雌二醇片/雌二醇地屈孕酮片组(西药组)、补肾活血方组(中药组)和补肾活血方联合雌二醇片/雌二醇地屈孕酮片组(联合组),各60例。观察三组治疗前后卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E_(2))、抗米勒管激素(AMH)、窦卵泡数(AFC)、卵巢体积、卵巢动脉和子宫动脉阻力指数(RI)、子宫内膜厚度的变化,比较三组中医证候评分及疗效。结果11例患者(4例来自西药组,3例来自中药组,4例来自联合组)退出研究。6个月后,三组FSH和LH均显著降低,E_(2)和AMH升高(P<0.05);西药组和联合组较中药组FSH降低更显著,E_(2)升高更显著(P<0.01)。治疗后,中药组和联合组卵巢体积增加(P<0.05),AFC显著增加(P<0.01),卵巢动脉RI显著降低(P<0.01);西药组卵巢体积增加不显著(P>0.05),AFC显著增加(P<0.05),卵巢动脉RI显著降低(P<0.05);三组子宫动脉RI均无显著改善(P>0.05)。三组子宫内膜厚度均显著增加(P<0.05),西药组和联合组较中药组增加更显著(P<0.01)。与治疗前相比,三组治疗后中医证候评分均显著降低(P<0.05),且中药组和联合组中医证候评分降低的程度大于西药组(P<0.05)。西药组总有效率为71.43%,中药组为82.46%,联合组为85.96%;联合组的疗效优于西药组(P<0.05)。结论补肾活血方能够通过平衡激素水平、促进排卵和修复子宫内膜对DOR患者产生良好的治疗效果,联合应用雌二醇片/雌二醇地屈孕酮片可能是治疗DOR的一种行之有效的治疗策略。