Huoxue Tongjiang decoction-resisted reflux esophagitis by activation stem cell factor/c-kit/interstitial cell of cajal pathway and regulating the T-helper 17/regulatory T-cells balance in rats

Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.

Meta-analysis of the efficacy and safety of Bushen Huoxue decoction in the treatment of Osteoporosis

Objective:To systematically evaluate the long-term efficacy of Bushen Huoxue Decoction combined with vertebroplasty(PVP or PKP)in the treatment of osteoporotic vertebral compression fractures(OVCF),in order to provide evidence-based reference for clinical application.Methods:To ensure the novelty of research data,a computer search was conducted between 2017 and February 2023 to publicly publish all randomized controlled studies and clinical trials at home and abroad on the treatment of OVCF with Bushen Huoxue Decoction combined with vertebroplasty published in CNKI,Wanfang,Vip,PubMed,CBM,and Cochrane libraries.Two researchers independently conducted literature screening and data extraction,evaluated the quality of randomized controlled trials included one by one according to the Cochrane collaboration network standards,and conducted a meta statistical analysis using RevMan5.3 for studies that met the inclusion criteria.Results:A total of 684 patients were included in 7 randomized controlled trials,including 342 patients in the observation group and 342 patients in the control group,with a ratio of 1:1;The meta-analysis results showed that in the observation group,the overall effective rate[RR=1.30,95%CI(1.14,1.47),P<0.001],visual analog pain(VAS)score[SMD=1.19,95%CI(0.77,1.61),P<0.0001],bone mineral density score[SMD=1.09,95%CI(0.15,2.04),P=0.02],COQOL score[SMD=0.99,95%CI(0.68,1.30),P<0.00001],OPG score[SMD=0.48,95%CI(0.18,0.77),P=0.002]The RANKL score[SMD=1.33,95%CI(1.00,1.65),P<0.0001]was significantly superior to the control group,with statistically significant differences.There was no significant difference in the Oswestry Disability Index(ODI)score[SMD=0.27,95%CI(-0.03,0.57),P=0.08],Cobb score[SMD=1.52,95%CI(-1.05,4.09),P=0.25],and vertebral height score[SMD=0.43,95%CI(-0.14,1.01),P=0.14].Conclusion:The results show that Bushen Huoxue Decoction combined with vertebroplasty has significant advantages in improving bone mineral density and alleviating pain in patients after OVCF,which is significantly superior to using OVCF alone.

Analysis on the Effect of Yiqi Huoxue Decoction Combined with Neuromuscular Electrical Stimulation in Improving ICU-Acquired Debility in Mechanically Ventilated Patients

Objective:To investigate the effect of Yiqi Huoxue decoction combined with neuromuscular electrical stimulation on improving intensive care unit(ICU)acquired debility in mechanically ventilated patients.Methods:50 patients who were admitted to the ICU and received mechanical ventilation treatment in our hospital from June 2022 to June 2023 and were complicated with ICU-acquired neurasthenia were selected,and randomly grouped using the randomized envelope method into two groups:control group with 25 patients who received neuromuscular electrical stimulation alone;observation group with 25 patients who received the traditional Chinese medicine Yiqi Huoxue decoction.Comparison indexes:treatment efficiency,degree of emotional recovery(APACHEⅡscore),muscle strength status(MRC score),motor status(FAC rating),and self-care ability(BI index score).Results:The treatment efficiency of patients in the observation group patients was higher as compared to those in the control group(P<0.05).There was no significant difference in the comparison of the results of the scores(ratings)of each index between the two groups before treatment(P>0.05).After the treatment,the APACHEⅡscores of patients in the observation group were significantly lower as compared to those in the control group,while the MRC scores,FAC ratings,and BI index scores were higher in the observation group than those of the control group patients(P<0.05).Conclusion:The combined application of Yiqi Huoxue decoction and neuromuscular electrical stimulation in the treatment of patients with ICU-acquired neurasthenia complicated by mechanical ventilation significantly enhanced the clinical efficacy,the patient’s muscle strength,motor status,and ability of self-care.Hence,it has high application value and is worthy to be popularized.

Liqi Huoxue dripping pill protects against myocardial ischemia-reperfusion injury via the PI3K/Akt/GSK-3β signaling pathway in rats

Background:Liqi Huoxue dripping pill(LQHXDP),a traditional Chinese drug for coronary heart disease,has a protective effect on the heart of rats with myocardial ischemia-reperfusion injury(MIRI)in previous studies;however,its mechanism of action remains unclear.The purpose of this study was to investigate the protective mechanism of LQHXDP on MIRI in rats and its relationship with the PI3K/Akt signaling pathway.Methods:In this study,Sprague-Dawley rats were pre-infused with LQHXDP(175 mg/kg/d)for 10 days.PI3K inhibitor LY294002(0.3 mg/kg)was intravenously injected 15 minutes before ischemia.The rat model of MIRI was established by ligating the left anterior descending coronary artery.Subsequently,cardiac hemodynamics,serum myocardial injury markers,inflammatory factors,myocardial infarct size,antioxidant indexes,myocardial histopathology,and phosphorylation levels of key proteins of PI3K/Akt signaling pathway were assessed in rats.Results:LQHXDP was found to improve cardiac hemodynamic indexes,reduce serum creatine kinase MB isoenzyme activity and cardiac troponin and heart-type fatty acid binding protein levels,lower serum interleukin-1 beta,interleukin-6 and tumour necrosis factorαlevels,reduce the myocardial infarct size and enhance the antioxidant capacity of myocardial tissue in MIRI rats.Pathological analysis revealed that LQHXDP attenuated the extent of myocardial injury and protected mitochondria from damage in MIRI rats.Immunoblot analysis revealed that LQHXDP increased the expression levels of p-Akt and p-GSK-3βin MIRI rat cardiomyocytes.PI3K inhibitor LY294002 could impair these effects of LQHXDP.Conclusion:LQHXDP attenuated myocardial injury,attenuated oxidative stress injury and reduced inflammatory response in MIRI rats,and its protective effects were mediated by activating of PI3K/Akt/GSK-3βsignaling pathway.

Effect of sitagliptin combined with Yiqi yangyin huoxue decoction on clinical efficacy and hemorheology in early diabetic nephropathy

BACKGROUND Early diabetic nephropathy(DN)is a complication of diabetes mellitus.It mainly affects kidney microvessels and glomerular function,and its timely and effective treatment is critical for early DN.However,the effects of treatments comprising simple Western medicine are not optimal.With the promotion and implementation of integrated Chinese and western medicine treatments,remarkable results have been achieved for many diseases.To this end,we explored the clinical efficacy of integrated traditional Chinese and western medicines for the treatment of early DN.AIM To investigate the effect of sitagliptin tablets combined with Yiqi yangyin huoxue decoction on clinical efficacy and hemorheology in patients with early DN.METHODS Through a retrospective analysis,123 patients with early DN were admitted to the endocrinology clinic of the Changzhou NO.7 People’s Hospital from January 2021 to October 2022 and were selected as study subjects.After rigorous screening,100 patients with early DN were enrolled.The control group(CG,n=50)and the observation group(OG,n=50)were divided according to the treatment method.The CG were treated with sitagliptin,and the OG were treated with sitagliptin plus the Yiqi yangyin huoxue decoction.Both groups were treated for 3 mo.For both groups,the baseline data and clinical efficacy were compared,and changes in blood glucose levels,lipid levels,renal function,and hematological indicators before(T0)and after(T1)treatment were assessed.RESULTS The total effective rate for the OG was 94.00%and that of the CG was 80.00%(P<0.05).After treatment(T1),the levels of fasting blood glucose,2 h postprandial glucose,total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol in OG patients were obviously lower than those in the CG(P<0.05),and cystatin C,homocysteine,urinary microalbumin,and blood creatinine values in OG patients were also obviously lower than those in the CG(P<0.05);erythrocyte deposition,plasma viscosity,whole blood high shear viscosity,and whole blood low shear viscosity were markedly lower in OG patients than in the CG(P<0.05).CONCLUSION Sitagliptin combined with Yiqi yangyin huoxue decoction has a remarkable effect when used to treat patients with early DN.Further,it is helpful in improving hemorheological indices and controlling disease progression.

Effect of Huoxue Yiqi recipe on proliferation,migration and tube formation of miR-484 overexpressed umbilical vein endothelial cells

Objective:To explore the possible mechanism of Huoxue Yiqi recipe promoting angiogenesis by targeting VEGF with miR-484.Methods:The model of miR-484 overexpressed in HUVEC was prepared and intervened with Huoxue Yiqi Recipe Freeze-dried powder.The effects of Huoxue Yiqi Recipe on proliferation,migration and tubular forming ability of HUVEC were separatly detected by CCK-8 method,cell scratch test and Matrigel three-dimensional forming test in vitro.The effect of Huoxue Yiqi Recipe on VEGFA mRNA expression was detected by real-time fluorescence quantitative PCR.Results:Compared with the control group,the proliferation and migration area of cells in miR-484 overexpression model group decreased,the length,number of branches and nodes involved in tube formation decreased,the tube formation ability decreased significantly,and the expression level of VEGFA mRNA decreased,with statistical significance.Compared with the model group,the cell proliferation ability,migration area,length,number of branches and nodes involved in tube formation,tube formation ability and expression level of VEGFA mRNA in the Huoxue Yiqi Prescription group were up-regulated,and the difference was statistically significant(P<0.05).Conclusion:MiR-484 inhibits the expression of VEGFA and the proliferation,migration and formation of HUVEC,and Huoxue Yiqi recipe has a certain negative regulation effect on this process,which may be a new target of Huoxue Yiqi recipe to promote angiogenesis.

Meta analysis and data mining of the method of yishenhuoxue in the treatment of nonproliferative diabetic retinopathy

Objective:To evaluate the efficacy and safety of the method of Yishen Huoxue in the intervention of nonproliferative diabetic retinopathy(NPDR)by Meta analysis and explore the medication regularity of Chinese Medicine(TCM)based on data mining.Methods:The related literature of TCM in the treatment of NPDR published in CNKI,VIP,WF,PubMed,the Cochrane Library,SinoMed,Embase were collected.The quality of the included literature was evaluated with reference to the Cochrane System Evaluators'Handbook,and statistical analysis was performed by applying Revman 5.4.1 software.After normalization of the Chinese medicine names,association rule analysis was performed by using SPSS Modeler 18,and then Cytoscape was used to produce complex network diagrams.Results:20 RCTs were included.Meta-analysis results showed that the method of Yishen Huoxue or Yishen Huoxue combined with western medicine were better than the control group in improving the total clinical efficiency[RR=1.21,95%CI(1.16,1.27),P<0.00001],TCM symptom efficacy[RR=1.28,95%CI(1.18,1.39),P<0.00001],and visual acuity[MD=0.11,95%CI(0.05,0.17),P=0.0001],HDL-C[MD=0.14,95%CI(0.03,0.25),P=0.02];reducing the number of fundus hemangiomas[MD=-3.51,95%CI(-5.73,-1.28),P=0.002],hemorrhagic spot area[MD=-0.70,95%CI(-0.95,-0.46),P<0.00001],CMT[MD=-35.31,95%CI(-55.47,-15.14),P=0.0006],FBG[MD=-0.39,95%CI(-0.72,-0.05),P=0.02],LDL-C[MD=-0.36,95%CI(-0.64,-0.08),P=0.01],whole high blood viscosity[MD=-0.43,95%CI(-0.75,-0.12),P=0.006],plasma viscosity[MD=-0.36,95%CI(-0.67,-0.06),P=0.02]and fibrinogen[MD=-0.50,95%CI(-0.81,-0.19),P=0.002].The differences were statistically significant.The 20 recipes entered involved a total of 70 herbal medicines.It is analyzed that the high-frequency drugs and the core drugsare gou qi,san qi,dan shen,haung qi,sheng di huang,et al.The association rule analysis summarizes the commonly used pairs including:sheng di huang-san qi,sheng di huang-gou qi,et al.Conclusions:Compared with western medicine treatment alone,the method of Yishen Huoxue or Yishen Huoxue combined with western medicine produce better effects,but it still needs to be verified by higher quality clinical studies.

Huoxue Rongluo Tablet reduces matrix metalloproteinase-9 expression in infarcted brain tissue

Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3：2：6：2：3：3：3：3. Huoxue Rongluo Tablet is a well-established and common pre- scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat- ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression.

Effect of JIANPI HUOXUE decoction on inflammatory cytokine secretion pathway in rat liver with lipopolysaccharide challenge

AIM： To evaluate the effect of Chinese traditional medicinal prescription, JIANPI HUOXUE decoction （JHD） on cytokine secretion pathway in rat liver induced by lipopolysaccharide （LPS）. METHODS： Twenty-four male SD rats were divided into normal group （n = 4）, model group （n = 10） and JHD group （n = 10） randomly. Rats in model group and JHD group were administrated with normal saline or JHD via gastrogavage respectively twice a day for 3 d. One hour after the last administration, rats were injected with LPS via tail vein, 50 μg/kg. Simultaneously, rats in normal group were injected with equivalent normal saline. After LPS stimulation for 1.5 h, serum and liver tissue were collected. Pathological change of liver tissues was observed through hematoxylineosin （H.E.） staining. Tumor necrosis factor alpha （TNF-α） in serum were assayed by enzyme linked immunosorbent assay （ELISA）. The protein expression of TNF-α, phosphorylated inhibit-κB （p-κB） and CD68 in liver were assayed by Western blot. The distribution of CD68 protein in liver was observed through immunohistochemical staining. The mRNA expression of TNF-α, interleukin-6 （IL-6）, CD14, toll-like receptor 2 （TLR2） and TLR4 in liver were assayed by real-time RT-PCR.RESULTS： Predominant microvesicular change, hepatocyte tumefaction and cytoplasm dilution were observed in liver tissues after LPS administration as well as obvious CD68 positive staining in hepatic sinusoidal. After LPS stimulation, serum TNF-α （31.35 ± 6.06 vs 12225.40 ± 9007.03, P 〈 0.05）, protein expression of CD68 （1.13 ± 0.49 vs 3.36 ±1.69, P 〈 0.05）, p-IκB （0.01 ±0.01 vs 2.07 ＋ 0.83, P 〈 0.01） and TNF-α （0.27 ± 0.13 vs 1.29 ± 0.37, P 〈 0.01） in liver and mRNA expression of TNF-α （1.96 ± 2.23 vs 21.45 ±6.00, P 〈 0.01）, IL-6 （4.80 ± 6.42 vs 193.50 ± 36.36, P 〈 0.01） and TLR2 （1.44 ± 0.62 vs 4.16 ± 0.08, P 〈 0.01） in liver were also increased significantly. These pathological changes were all improved in .1HD group. On the other hand, TLR4 mRNA （1.22 ± 0.30 vs 0.50 ± 0.15, P 〈 0.05） was down-regulated and CD14 mRNA increased but not significantly after LPS stimulation. CONCLUSION： JHD can inhibit cytokine secretion pathway induced by LPS in rat liver, which is probably associated with its regulation on CD68, p-IκB and endotoxin receptor TLR2.

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.

Tongqiao Huoxue Decoction combined with butylphthalide in the treatment of acute ischemic stroke and its effect on VEGF

Objective:To study the effect of Tongqiao Huoxue Decoction combined with butylphthalide soft capsules on acute ischemic stroke and its effect on serum vascular endothelial growth factor(VEGF).Methods:There are 76 patients with acute ischemic stroke(Acute Ischemic Stroke,AIS),including 38 cases in the control group and the observation group.All patients were treated with conventional treatment methods for this disease.On this basis,the control group was given butylphthalide soft capsules orally,0.2g/time,3 times a day,and the observation group was given Tongqiaohuoxue Decoction on the basis of oral butylphthalide soft capsules.One dose a day,two times in the morning and evening.All patients were treated for 20 days as a course of treatment.The clinical efficacy of the two groups of patients were compared,the collateral circulation rate before and after treatment,NIHSS,MoCA and MMSE,hemorheology(plasma viscosity,fibrinogen,whole blood high and low shear viscosity),VEGF levels and the occurrence of adverse reactions.Results:The effective rate of the two groups was 92.1%in the observation group and 73.7%in the control group,which was significantly different(P<0.05).The collateral circulation patency rate was 86.8%in the observation group and 57.9%in the control group,which was significantly different(P<0.05).After treatment,the MoCA,MMSE scores and VEGF levels of the observation group were significantly higher than those before the treatment and the control group,with significant differences(P<0.05).The NIHSS score and hemorheology were improved compared with those before the treatment and the control group.There are significant differences(P<0.05).Conclusion:Tongqiao Huoxue Decoction combined with butylphthalide soft capsules can significantly improve collateral circulation,hemorheology,neurological and cognitive functions in patients with acute ischemic stroke.The mechanism may be related to the increase of VEGF levels and the promotion of neovascularization.

Treatment of postoperative gastric cancer with Fuzheng Huoxue anticancer prescription

AIM Study on the effects of Fuzheng Huoxue anticancer prescription (Traditional Chinese Medicine) in treating gastric cancer. METHODS Sixty nine patients with gastric cancer of mid or late stage were confirmed histologically. They were divided into two groups. The treatment group included 35 cases (26 males and 9 females, 2 cases aged from 33～40 years, 18 from 41～60, 15 from 61～75, mean 58 4 years). The control group included 23 males and 11 females, 4 aged 33～40 years, 16 41～60, 14 61～75, averaging 56 8 years. The two groups were not significantly different in sex, age, clinical and pathological stages, operation mode, etc. The two group were given similar treatment. The treatment group was given Fuzheng Huoxue anticancer prescription. The cell line SGC 7901 was inoculated to the back of 30 nude mice under sterile condition. The nude mice were allocated randomly into control, traditional Chinese medicine and chemotherapeutic groups with 10 mice in each group with similar weight. Each nude mouse in control group received 0 5ml saline/day. The Fuzheng Huoxue anticancer prescreption was given to the traditional Chinese medicine group, 0 5ml/day (containing 1 5g crude drug) chamotherapentic group was injected with 1mg 5 Fu intraperitoneally once a week for 8 weeks. RESULTS Before treatment, OKT8 was 45 94±8 45%, OKT4/OKT8 was 0 89±0 19, AT Ⅲ was 29 9mg/dl±7 9mg/dl, Fa was 50 4%±24 4%, β TG was 91 0ng/dl±25 9ng/dl in treatment group; OKT8 was 49 21%±6 60%, OKT4/OKT8 was 0 94±0 20, AT Ⅲ was 32 3mg/dl±7 2mg/dl, Fa was 57 3%±24 6%, β TG was 87 5ng/dl±34 2ng/dl in controls before treatment. After treatment, OKT8 was 33 52%±7 80%, OKT4/OKT8 was 1 47±0 51, AT Ⅲ was 38 8mg/dl±5 5mg/dl, Fa was 102 6%±31 6%, β TG was 62 3ng/dl±15 1ng/dl in treatment group and OKT8 was 42 22%±7 07%, OKT4/OKT8 was 1 12±0 24, AT Ⅲ was 30 9mg/dl±8 0mg/dl, Fa was 64 6%±26 9%, β TG was 67 0ng/dl±42 1ng/dl in controls. After treatment, the T lymphocyte′s immunologic function of the patients with gastric cancer was significantly improved in the treatment group ( P <0 01). The hypercoagulability was improved ( P <0 001). OKT4/OKT8 ratio, antithrombin Ⅲ (AT Ⅲ), fibrinolytic activity, etc. were all normalized. The one year (86%), 3 year (69%) and 5 year (40%) suvival rates were increased as compared with controls, ( P <0 05). The mean tumor weighted 0 895g±0 289g in controls, 0 433g±0 177g in traditional Chinese medicine group and 0 357g±0 142g in chemotherapeutic group. The tumor inhibitory rates were 51 6% and 60 1% in traditional Chinese medicine group and chemotherapeutic group, respectively, significantly better than in the controls ( P <0 001). The mean tumor weight was 24 68±1 93g in traditional Chinese Medicine group, significantly higher than that in treatment group (22 96g±1 87g) and the controls (22 47g±2 18g). CONCLUSION Fuzheng Huoxue anticancer prescription can not only replenish vital fuction (Zheng qi), improve hypercoagulatory state, improve immunologic function and extend the survival of patient, but may also have direct inhibitory action on gastric tumor growth without side effects and toxicity.

Yiqi Huoxue Decoction attenuates ischemia/hypoxia-induced oxidative stress injury in H9c2 cardiomyocytes

Objective:Yiqi Huoxue Decoction (YQHX) has been widely used for clinical treatment of ischemic heart disease.While oxidative stress plays a key role in the pathogenesis of ischemic heart disease,the function and molecular mechanism underlying antioxidative protective effects of YQHX on H9c2 cardiomyocytes against ischemia/hypoxia (I/H) have yet to be well clarified.Methods:H9c2 cells were subjected to 12 h of hypoxia with serum-free conditions and then treated with or without YQHX (100-400 μg/mL).Cell viability was examined using a CCK-8 assay.Maleic dialdehyde (MDA) and superoxide dismutase (SOD) activity were detected using commercial kits.Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were measured using fluorescence microscopy and confocal laser-scanning microscopy,respectively.Ultrastructural details of mitochondria in H9c2 cells were observed using transmission electron microscopy.The antioxidative protective pathway was assessed by measuring mRNA and protein expression of Nrf2 and HO-1,as well as AMPK activation.Results:I/H injury gradually induced oxidative stress.Treatment with YQHX significantly increased cell viability and reversed I/H-induced oxidative stress,including reducing the production of oxidative stress products (ROS and MDA),increasing SOD levels,improving mitochondrial morphology,and increasing mitochondrial membrane potential.YQHX was also observed to increase I/H-induced expression of Nrf2 and HO-1,and the activation effects of YQHX were blocked by an AMPK inhibitor.In addition,HPLC analysis showed that YQHX contained two active antioxidative constituents (calycosin and ferulic acid).Conclusion:The results suggest that anti-oxidative effects exerted by YQHX in H9c2 cardiomyocytes may be linked to upregulation of the AMPK-mediated Nrf2/HO-1 pathway.

Cardioprotective effect of Yiqi Huoxue granule through regulation of mitophagy after myocardial infarction in rats

Objective:To investigate the cardioprotective effect of Yiqi Huoxue granule(YQHXG)in the regulation of autophagy in rats induced with myocardial infarction(MI).Methods:An acute MI animal model was established by ligation of the left anterior descending branch of the coronary artery in Sprague-Dawley rats.Besides,20 rats received sham operation were classified into a control group.The remaining 59 rats were randomly divided into MI model group(n=19),YQHXG group(n=20),and perindopril group(n=20).Relevant indicators on days 7 and 28 were observed in each group.Left ventricular function was determined by echocardiography.The structure and morphology of mitochondria,and the number of autophagic vesicles,were observed by transmission electron microscopy.The mRNA and protein expression levels of LC3,FUNDC1,Beclin-1,and BNIP3 were examined in the tissue of the MI marginal area.Results:Compared with the MI model group,YQHXG showed obvious improvements in cardiac functions.Observing the microscopic morphology of the heart tissue,myocardial tissue damage attenuated,autophagic signs of autophagosomes and autolysosomes reduced,vacuolization in mitochondria mitigated,and mitochondria arranged in order.YQHXG could reduce the degree of tissue lesion after MI and regulate the expression of autophagy-related molecules at different stages.On Day 7,YQHXG significantly downregulated the expression of Fundc1,Becn1,Bnip3 mRNA and reduced the levels of FUNDC1,Beclin-1,BNIP3,and LC3 B proteins expression(all P<.001).On Day 28,YQHXG could upregulate the expression of Becn1,Fundc1 and Bnip3 mRNA and increased the levels of the corresponding proteins expression(all P<.001).Besides,it also increased LC3 B protein expression level(P=.0344).Conclusion:YQHXG regulated the expression of mitochondrial autophagy-related factors in myocardial tissue and mitochondrial autophagic activity at different stages to protect the heart following MI.

Yiqi Huoxue Decoction modifies the expression of myocardial cytoskeleton-associated proteins by regulating the AMPK signaling pathway in H9c2 cells exposed to hypoxic conditions

Background:In myocardial ischemia,hypoxia leads to destruction of the cytoskeleton,and especially the imbalance of microtubule polymerization-depolymerization,which seriously affects the structure and function of cardiomyocytes.We previously showed that a Yiqi Huoxue Decoction (YQHX) improves mitochondrial function and decreases anti-oxidative effects in hypoxia-induced H9c2 cell injury.Therefore,in this study we investigated whether YQHX protects against hypoxia-induced damage by decreasing damage to the cardiac cytoskeleton.Methods:After reaching 70%-80% confluence,H9c2 cells were synchronized in serum-free Dulbecco's Modified Eagle Medium for 6 hours,then divided into control,model,and YQHX (100,200,400 μg/mL) groups,which were then grown in a hypoxic atmosphere for 12 hours.Cardiac cell viability was assessed using an xCELLigence system.The levels of lactate dehydrogenase,maleic dialdehyde,and superoxide dismutase in H9c2 cell supernatants were measured.Hoechst 33258 staining was employed to observe cardiac cell apoptosis.Confocal microscopy,immunofluorescence,and western blot analysis were performed to evaluate the protective effects of the YQHX against hypoxia-induced injury in the H9c2 cell line.Results:Cells that were pretreated with YQHX were more able to maintain their microtubule structure in the early stages of hypoxia and had better myocardial fitness in response to hypoxia compared with cells that were not pretreated.However,hypoxia-induced upregulation of α-tubulin and β-tubulin expression antagonized the protective effect of YQHX (100 μg/mL).In addition,YQHX (100 μg/mL) treatment significantly upregulated MAP4 protein expression (P =.003) and downregulated p-AMPKα protein expression (P <.001) compared with the model group.Conclusion:The results indicate that YQHX plays a role in protecting against oxidative stress injury and apoptosis in H9c2 cells.Notably,our results suggested that the YQHX could mitigate the damage to the cardiac cytoskeleton and the dysregulation of AMPK-related protein signaling pathways that are induced by hypoxia.

Effects of yiqi yangyin huoxue therapy on IgA nephropathy: a systematic review and meta-analysis of randomized controlled trials

Objective To assess the efficacy and safety of Yiqi Yangyin Huoxue therapy (YYHT) for the treatment of IgA nephropathy. Methods Databases articles about YYHT in treating IgAN patients were searched through February 2018. Comparisons were YYHT alone or YYHT in combination with western medicine as experimental intervention, and western medicine as the control. Randomized controlled trials (RCTs) were selected. Cochrane collaboration tool was used for assessing risk of bias to evaluate methodologies. RevMan 5.3 software was applied to analyze the data of included trials. Results A total of 21 studies involving 1473 patients were included. Meta-analysis results demonstrated that YYHT alone or YYHT in combination with western medicine were more efficacious than only western medicine in decreasing proteinuria [MD =-0.41, 95% CI (-0.53,-0.29), P < 0.00001] and the urine red blood cells [MD =-7.46, 95% CI (-9.28,-5.64), P < 0.00001]. There also showed improvement in the clinical total effective rate [OR = 2.78, 95% CI (2.14, 3.61), P < 0.00001] between the two groups. Some of the included trials did not report the adverse events. Conclusions Current evidence shows that YYHT can reduce proteinuria and urine red blood cells and improve the total efficacy rate. Since poor quality and publication bias of some included trials, more evidence-based medicine studies needed to define the role of YYHT in the treatment of IgAN.

Multicenter Randomized Double-Blind Controlled Clinical Study of Huoxue Tongluo Recipe(活血通络方)External Washing in the Treatment of Chemotherapy-Induced Peripheral Neuropathy

Objective: To objectively evaluate the efficacy of Huoxue Tongluo Recipe(活血通络方) in the treatment of chemotherapy-induced peripheral neuropathy(CIPN).Methods: A multicenter, randomized, double-blind, block, and parallel-controlled study was conducted in which 184 subjects who met the inclusion criteria were randomized into a trial group(92 cases), a control group(46 cases), a placebo group(46 cases) at a 2:1:1 ratio, respectively.Huoxue Tongluo Recipe(活血通络方) granules, Huangqi Guizhi Wuwu Decoction(黄芪桂枝五物汤) instant granules, placebo instant granules were given for hand and foot soaking, with water temperature 38 ℃-45 ℃, soaking for 20 minutes and the intervention time was 14 days.Results:(1) The total effective test drug was 41.30%, the control group was 32.61%, and the placebo group was 32.61%.There was no significant difference in the efficiency of the 3 groups by CMH chi-square test(P>0.05);(2) In the statistics of previous chemotherapy regimens including oxaliplatin or paclitaxel as stratification factors, the overall efficiency of the trial group was significantly different from the other 2 groups.Conclusion: Huoxue Tongluo Recipe(活血通络方) external washing can improve the peripheral nerve injury caused by chemotherapy to some extent, especially in patients with previous chemotherapy regimen including oxaliplatin and paclitaxel.

Meta-Analysis of Bushen Huoxue Method in the Treatment of Recurrent Spontaneous Abortion Due to Prethrombotic State

Objective:To evaluate the effectiveness and safety of Bushen Huoxue prescription in the treatment of recurrent spontaneous abortion(RSA)due to prethrombotic state(PTS).Methods:Databases such as CNKI,WanFang,VIP,CBM,PubMed,Embase,and Cochrane Library were searched for randomized controlled trials on Bushen Huoxue prescription in treating RSA due to PTS from inception to March 2021;meta-analysis was performed by RevMan Version 5.3.0 following quality evaluation.Results:Seven trials were included,with 496 patients;the meta-analysis indicated that Bushen Huoxue prescription has advantages on the improvement of total clinical effective rate[RR=1.22,95%CI(1.10,1.35),Z=3.80(P=0.0001)],embryo survival rate at pregnancy of 12 weeks[RR=1.25,95%CI(1.10,1.41),Z=3.53(P=0.0004)],D-dimer levels[SMD=-1.59,95%CI(-2.20,-0.97),Z=5.07(P<0.00001)],and fibrinogen levels[MD=-1.00,95%CI(-1.29,-0.70),Z=6.61(P<0.00001)],but the statistical heterogeneity was significant;in terms of incidence of adverse reactions,there was no statistical difference between Bushen Huoxue prescription and western medicine.Conclusion:Compared with western medicine alone,Bushen Huoxue prescription alone or in combination with western medicine showed significant advantages in improving the overall clinical efficiency,embryonic survival rate at 12 weeks of pregnancy,and reducing D-dimer values as well as fibrinogen levels,without any significant difference in the incidence of adverse effects;however,the number of included studies is small and there are drawbacks,such as small sample size and low quality;therefore,high-quality clinical studies with large sample size and rigorous trial designs are needed in the future to provide a reliable basis for the effectiveness and safety of TCM in reducing the incidence of RSA due to prethrombotic state.

Effect and Mechanism of Bushen Huoxue Recipe on Ovarian Reserve in Mice with Premature Ovarian Failure

The aim of the present study was to explore the effect and mechanism of Bushen Huoxue recipe（BHR） on ovarian reserve in mice with premature ovarian failure（POF）. Mice were divided into 3 groups： normal group, model group and BHR group. Intraperitoneal injection of cyclophosphamide was performed to create the POF model. Primordial follicular（PDF） number, ovarian wet weight, ovarian index, and estrous cycle were analyzed to evaluate the effect of BHR on POF. Meanwhile, the m RNA and protein level of Mouse Vasa Homologue（MVH） in the bone marrow, peripheral blood and ovary were detected, to explore the underlying mechanism of the treatment efficacy of BHR on ovarian reserve. By the time of BHR treatment for 28 days, BHR increased the PDF number and shortened the estrous cycle of POF mice. BHR also decreased the m RNA level of MVH in the bone marrow, and increased m RNA and protein level of MVH in the ovary of POF mice. Our results demonstrated a treatment efficacy of BHR on POF mice, and revealed that BHR might repair the dysfunction of germline stem cells in the bone marrow, and thus to improve the ovarian reserve and enhance the ovarian function of POF mice through neo-oogenesis.

Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction

OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.METHODS The patients with coronary heart disease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months,and the changes of cardiac function were observed.61 serum samples(including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group)were analyzed by non labeled proteomics.The disease group was used as the control group,and the protein with expression level difference of more than 1.2 folds(P<0.05)was screened.The molecular function,biological pathway and protein interaction of the different proteins were analyzed by bioinformatics,so as to identify the molecular and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction,regulate blood glucose and blood lipid levels,prolong thrombin time,and improve heart function.The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group.Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1,alpha-2 and other proteins to act on HDL assembly,platelet degradation,PI3K Akt signaling pathway,and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome.CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syndrome of coronary heart disease.It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins.This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.