Evaluating the effect and mechanism of Yiqi Huayu Jiedu decoction combined with FLOT regimen neoadjuvant chemotherapy for the patients with locally advanced gastric cancer:protocol for a prospective,double-arm,randomized controlled clinical trial

Background:Neoadjuvant chemotherapy plays a vital role in the treatment of advanced gastric cancer(GC),however,optimizing its effectiveness remains an important research focus.Traditional Chinese medicine(TCM),a promising adjunctive therapy,has shown enhanced clinical outcomes when combined with postoperative adjuvant chemotherapy.Therefore,this study is designed to evaluate the clinical efficacy of Yiqi Huayu Jiedu decoction combined with neoadjuvant chemotherapy FLOT in the treatment of advanced GC.Methods:This study is a prospective,double-arm,randomized controlled trial.It involves a total of 260 patients diagnosed with advanced GC,who will be randomly assigned to two groups-a TCM treatment group and a control group,each comprising 130 patients.All patients will receive standard FLOT chemotherapy,and patients in the TCM treatment group will additionally receive TCM treatment with Yiqi Huayu Jiedu decoction.After four cycles of chemotherapy,GC D2 radical surgery will be performed.The primary objective is to evaluate the postoperative pathological response rate of the tumor.The secondary objectives include evaluating the perioperative nutritional status,the efficacy of TCM syndrome,and adverse events associated with both chemotherapy and surgery.Discussion:Currently,no trials have investigated the impact of TCM in combination with neoadjuvant chemotherapy on the preoperative treatment in patients with advanced GC.Accordingly,it is imperative to conduct this prospective study to evaluate the clinical efficacy and safety of this regimen,meanwhile providing high-level clinical evidence for TCM combined with neoadjuvant chemotherapy and introducing an innovative regimen for preoperative comprehensive treatment of GC.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.

Therapeutic effects of Buzhong Yiqi decoction in patients with spleen and stomach qi deficiency after routine surgery and chemotherapy for colorectal cancer

BACKGROUND According to the theory of traditional Chinese medicine(TCM),the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry.After surgery and chemotherapy,patients with colorectal cancer often develop spleen and stomach qi deficiency syndrome,leading to decreased immune function.Buzhong Yiqi decoction,a classic TCM prescription,has the effect of tonifying middle-jiao and invigorating qi,boosting Yang,and suppressing immune-related inflammation.Moreover,it is widely used in the treatment of spleen and stomach qi deficiency syndrome.AIM To investigate the effect of Buzhong Yiqi decoction on spleen and stomach qi deficiency in patients with colorectal cancer.METHODS One hundred patients with colorectal cancer who underwent preoperative chemotherapy and laparoscopy at The First TCM Hospital of Changde from January 2022 to October 2023 were retrospectively analyzed.The patients were divided equally into control and observation groups.Both groups underwent conventional rehabilitation surgery,and the observation group was supplemented with Buzhong Yiqi decoction.SPSS 26.0 was used for statistical analyses.Theχ2 test was used for univariate analysis;independent sample t-tests were used in all cases.RESULTS No significant differences were observed preoperatively in the general characteristics of the two groups.Fourteen days post-surgery,the abdominal distension,emaciation,loose stool,loss of appetite,and vomiting scores were significantly lower in the observation group than in the control group(P<0.05).Immune function and interleukin(IL)-10 levels in the observation group were significantly higher than those of the control group,whereas IL-6,tumor necrosis factor-α,and C-reactive protein levels,tumor biological indexes,and adverse reactions in the observation group were significantly lower than those of the control group(P<0.05).One month after surgery,the patients’quality of life in the observation group was significantly higher than that of the patients in the control group(P<0.05).CONCLUSION Buzhong Yiqi decoction can regulate inflammatory responses and metabolic processes by enhancing immune function,thereby promoting overall immune nutrition and restoring the body’s balance.

Effect of Qingre Huayu Decoction on Autophagy and Apoptosis of Neurons in Rats with Ischemic Brain Injury by Regulating Ca^(2+)/CaMKKβ-AMPK-mTOR Pathway

[Objectives]To explore the neuroprotective mechanism of Qingre Huayu Decoction on rats with acute cerebral ischemia injury.[Methods]SD rats were divided into sham operation group,ischemia model group,low,medium and high dose groups of Qingre Huayu De-coction,with 10 rats in each group.Referring to the MCAO operation model,both the sham operation group and the model group were given normal saline by gavage,and the Qingre Huayu Decoction group was given different doses of Qingre Huayu Decoction by gavage.After the op-eration,the rats were scored for neurological deficit,neurons were stained with HE,apoptotic cells were detected with TUNEL,and the levels of autophagy and apoptotic proteins in the Ca^(2+)/CaMKKβ-AMPK-mTORpathway in brain tissue were detected with Western-blot.[Results]Compared with the model group,the neurological function score of Qingre Huayu Decoction Group decreased significantly(P<0.05),the pathological damage of neurons in Qingre Huavu Decoction Group decreased.the proportion of apoptosis-positive cells detected by TUNEL de-creased(P<0.05),and the expression of CaMKKβand AMPK increased,expression of mTOR decreased,expression of Beclin-1 and LC3 increased,and expression of Caspase-3decreased in Qingre Huayu Decoction Group(P<0.05).[Conclusions]Qingre Huayu Decoction may play a neuroprotective role by activating Ca^(2+)/CaMKKβ-AMPK-mTOR pathway and regulating the level of apoptosis and autophagy.

Protective effect of Liangxue Huayu decoction on human retinal pigment epithelial cell(ARPE-19)injury induced by hypoxia through autophagy pathway

Background:Exploring the protective mechanism of the Liangxue Huayu(LXHY)decoction on human retinal pigment epithelial(RPE)cells induced by hypoxia through the autophagy pathway.Methods:The appropriate LXHY decoction concentration was determined by CCK-8.ARPE-19 cells were divided into the normal control group(A group),CoCl_(2)group(B group),3-Methyladenine(3-MA)group(treated with 3-MA(the inhibition of autophagy pathway))(C group),blank serum(BS)group(D group),LXHY drug-contained serum(DCS)group(E group),and Rapamycin(RAP)group[treated with LXHY drug-contained serum combined with rapamycin group(the activation of autophagy pathway)](F group).Counting the number of autophagosomes and autolysosomes in each group of cells under transmission electron microscopy.After infection of cells in each group by mRFP-GFP-LC3 fusion protein adenovirus,the strength of autophagic flux was detected.The mRNA expression levels of LC3 and Beclin-1 were detected by Q-PCR.Results:CCK-8 assay results showed that LXHY DCS could inhibit the cell proliferation of ARPE-19 under hypoxia(all P<0.05).As the transmission electron microscopy assay result showed,compared with the normal control group,the number of autolysosomes was significantly increased in the CoCl_(2)group(P<0.05).Compared with CoCl_(2)group,the number of autolysosomes was significantly reduced the 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.001).As autophagic flux assay result showed,compared with the normal control group,the level of autophagosomes and autolysosomes were significantly risen in CoCl_(2)group(all P<0.001).Compared with the CoCl_(2)group,the level of autophagosomes and autolysosomes were significantly fell down in 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.05).The level of autolysosomes in the LXHY drug-contained serum group was lower than in the blank serum group(P<0.05).Compared with the LXHY drug-contained serum group,the levels of autophagosomes and autolysosomes were significantly risen in the LXHY drug-contained serum combined with the rapamycin group(all P<0.05).As the Q-PCR result showed,compared with the normal control group,the expression of LC3 and Beclin-1 mRNA were significantly reduced in the CoCl_(2)group(all P<0.001).Compared with the CoCl_(2)group,the expression of LC3 mRNA were significantly increased in the 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.001).Beclin-1 mRNA expression was increased significantly(all P<0.001)in the blank serum group and the LXHY drug-contained serum group.And Beclin-1 mRNA expression in the LXHY drug-contained serum group was statistically significant increased than blank serum group(P<0.001).In the LXHY drug-contained serum combined with the rapamycin group,the LC3 and Beclin-1 mRNA expression was reduced significantly compared with the LXHY drug-contained serum group(all P<0.001).Conclusion:The LXHY DCS has the ability to protect the human retinal pigment epithelial cell(ARPE-19)damage under hypoxia through the autophagy pathway.

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.

Effect of Buzhong Yiqi Decoction (补中益气汤) on Murine Liver Damage Induced by Food Allergy

Objective: To investigate the effect of Buzhong Yiqi decoction (补中益气汤, BZYQD) on liver damage induced by food allergy in mice. Methods: Nc/Jic strain mice with high levels of serum IgE were sensitized by ovalbumin (OVA), and then divided into two groups and respectively treated with BZYQD (treated group) or normal saline (model group). Samples of serum, liver tissues and small intestine were collected two weeks later, and another group of non-sensitized mice was set as the normal group. The levels of serum alanine aminotransferase (ALT) were measured with spectrophotometry. The liver tissue and small intestine were stained with hematoxylin and eosin (HE) for pathologic analysis. The liver samples were also subjected to analysis of CD4-T helper cell and cytokine (interleukin-4, IL-4, interleukin-6, IL-6) expression with immunohistochemical (avidin-biotin complex, ABC) method. Results: Serum ALT levels decreased and obvious pathologic improvements were seen in the mice treated with BZYQD. And compared with the model mice, the number of positive cells of IL-4, IL-6 and CD4 cell decreased significantly in those treated with BZYQD. Conclusion: BZYQD can effectively decrease the production of cytokines associated with allergic reaction in the liver of mice thus effective in treating liver damage caused by food allergy.

Clinical Observation of Jiawei Buzhong Yiqi Decoction in the Treatment of Obese Polycystic Ovarian Syndrome

[Objectives] To observe the clinical efficacy of Jiawei Buzhong Yiqi Decoction in the treatment of polycystic ovarian syndrome(PCOS).[Methods]Obese patients with PCOS were recruited for the study in September 2014-December 2016 from Chinese medicine gynecological clinic in the affiliated hospital of Hubei University of Medicine.All these patients were given one dose of Jiawei Buzhong Yiqi Decoction one time a day for three months.Body mass index(BMI) was measured before and after treatment.Sex hormone levels and ovulation were measured,and the improvement of clinical symptoms was compared before and after treatment.[Results] After treatment,the levels of BMI and serum luteinizing hormone(LH),testosterone(T) were significantly decreased,and the level of serum estradiol(E2) was significantly higher than that before treatment.Ovarian enlargement and polycystic changes,menstrual cycle,menstrual flow and menstrual period were improved in varying degrees.[Conclusions] Jiawei Buzhong Yiqi Decoction has a good clinical effect in the treatment of obese PCOS.

Determination of Salvianolic Acid B in Yiqi Huayu Prescription by HPLC

[Objectives]To determine the content of salvianolic acid B in Yiqi Huayu Prescription by HPLC.[Methods]The chromatographic column was ZORBAX Eclipse Plus C 18(4.6 nm×250 nm,5μm);the mobile phase was acetonitrile-0.1%phosphoric acid(21:79),the detection wavelength was 286 nm,the column temperature was 30℃,and the flow rate was 1.0 mL/min.A method for determination of salvianolic acid B in Yiqi Huayu Prescription was established.[Results]The linear relationship of salvianolic acid B was good in the range of 0.0214-0.4064 mg/mL.The regression equation was Y=5995.98984 X-0.07332,r=0.9999.The average recovery rate was 98.88%(RSD=1.6%).[Conclusions]The method is reliable,accurate and specific,and can be used for the determination of salvianolic acid B in Yiqi Huayu Prescription.

Intervention of Peiyuan Huayu Decoction on the neuron damage in model rats with acute subdural hematoma

Objective:To study the intervention effect of Peiyuan Huayu Decoction on the neuron damage in model rats with acute subdural hematoma (ASDH).Methods: 160 SD rats were randomly divided into four groups, and the ASDH model rats were made by stereotactic autoblood injection, and sham operation group received craniotomy without blood injection. Sham operation group and model group were normally bred after model establishment, and 6 h after model establishment, the treatment group received intragastric administration of Peiyuan Huayu Decoction, and control group received intragastric administration of Piracetam Tablets, 1 time a day. On the 1d, 3d, 5d and 7d after model establishment, the general conditions of rats (activity, food intake and mental state) were observed, blood was collected via auricula dextra, ELISA method was used to determine peripheral plasma NSE and S100β protein contents, routine HE staining was conducted after perfusion fixation, the neurons in blood injection side of brain tissue were counted, and the neuron damage was observed.Results: 26 rats were dead in the experiment. The general conditions of sham operation group were significantly better than those of other groups, treatment group was significantly better than model group and control group on the 5d group (P<0.05), and there was no significant difference on the 1d, 3d and 7d (P>0.05);neuron count of sham operation group was basically stable, treatment group was not different from model group and control group on the 1d (P>0.05), treatment group was better than model group (P<0.05), and not different from control group (P>0.05) on the 3d, and treatment group was better than model group and control group on the 5d and 7d (P<0.05);peripheral plasma S100β protein and NSE contents of sham operation group were at lower levels, treatment group was not significantly different from model group and control group on the 1d (P>0.05), S100β protein and NSE contents decreased significantly on the 3d, and treatment group was significantly different from model group and control group (P<0.05), S100β protein and NSE contents increased on the 5d and 7d, the increase in treatment group was slower than that in model group and control group, and there was significant difference (P<0.05).Conclusion:Peiyuan Huayu Decoction has obvious protective effect on the neurons in ASDH model rats, and this effect may be based on the inhibition of secondary neuron damage.

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.

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.

Clinical observation of treatment with Yiqi Jianpi decoction combined with FOLFOX4 for the postoperation patients of colorectal cancer

Objective: The aim of the study was to observe the clinical efficacy with Yiqi Jianpi decoction combination with FOLFOX4 for the postoperative patients of colorectal cancer (CRC). Methods: Eighty-five patients were randomly divided into two groups. The treated group (n = 41) received Yiqi Jianpi decoction combined with FOLFOX4 chemotherapy and the control group (n = 44) received FLOFOX4 chemotherapy alone. A treatment course of 6 months was applied to both groups. Results: The life quality, symptomatic improvement and adverse side effects reducing in the treated group were better than those of the control group. Conclusion: Yiqi Jianpi decoction combination with FOLFOX4 chemotherapy is effective in the treatment of the postoperative patients with colorectal cancer.

Hemostatic mechanism of the effect of Jianpi Yiqi Shexue decoction on vascular factors in immune thrombocytopenia model mice

Objective: To explore the hemostatic mechanism of Jianpi Yiqi Shexue decoction(JYSD) by regulating vascular factors in an immune thrombocytopenia(ITP) mouse model.Methods: An ITP mouse model was established by the passive-immune modeling method, and interventional drugs used were prednisone tablets and JYSD. The platelet count;vascular activity-related factors v WF, VCAM-1, and TM;and VEGF and b FGF were used as observational indicators.Results: On the 8th day of administration, compared with the model group, platelet counts in the prednisone and JYSD groups increased(both P <.001). Compared with the control group, the levels of v WF, VCAM-1, and TM in the other groups were lower(all P <.05). The VCAM-1 level in the JYSD group was higher than that in the prednisone group(P =.012), but without significant difference compared with the model group(P =.051). The TM level in the JYSD group was the lowest(vs. the model group,P =.047;vs. the prednisone group, P =.006). Compared with the control group, the IOD values of VEGF and b FGF in the other three groups were lower(all P <.01). The IOD values of VEGF in the prednisone and JYSD groups were both higher than those in the model group(P =.002 and P <.001, respectively). The IOD values of b FGF among the model, prednisone, and JYSD groups were not statistically significant(P >.05).Conclusion: A vascular factor disorder is involved in the pathogenesis of ITP. JYSD can increase the platelet count, upregulate VEGF expression, and reduce the TM level. JYSD has the same effect as prednisone tablets in regulating platelet, v WF, VEGF, and b FGF, with a stronger effect in normalizing VCAM-1 and TM levels. The hemostatic mechanism of JYSD is closely related to the effective balance of vascular factors.

Effects of Jiawei Buzhong Yiqi Decoction on the Endometrial Receptivity of Rats with Polycystic Ovary Syndrome

[Objectives]The study aims to discuss the effects of Jiawei Buzhong Yiqi Decoction on the endometrial receptivity of rats with polycystic ovarian syndrome(PCOS).[Methods]Adult female SD rats were selected and randomly divided into the model group and control group.In the model group,the PCOS model was established by using the method of Poretsky L.Rats in the control group were given physiological saline intervention at the same time.The successfully modeled rats were randomly divided into the PCOS group and traditional Chinese medicine group.Among them,rats in the Chinese medicine group were given Jiawei Buzhong Yiqi Decoction by gavage;rats in the model group and the control group were given normal saline for 14 d.All rats were killed by anesthesia after the last administration,and serum and uterine specimens were collected.Serum sex hormones(including T,E_(2),and P),glucose and insulin levels were detected;the equivalent diameter and area of endometrial gland and gland cavity,and the endometrial thickness of rats were measured;the expression of endometrial leukemia inhibitory factor(LIF),integrinαvβ3 protein and mRNA was detected by using Elisa and RT-PCR methods.[Results]The serum T,glucose,and insulin levels of rats in the PCOS group were significantly higher than those of the control group and the traditional Chinese medicine group,and there was no significant difference in the above indicators between the control group and the traditional Chinese medicine group;there was no significant difference in the E_(2) and P levels between the three groups.The equivalent diameter and area of endometrial gland and gland cavity,and the endometrial thickness of rats in the PCOS group were lower than those of the control group and the traditional Chinese medicine group;there was no significant difference in the above indicators between the traditional Chinese medicine group and the control group.The expression of LIF,integrinαvβ3 protein and mRNA in the endometrium of rats in various groups was basically the same.The expression of LIF and integrinαvβ3 in the endometrium of rats in the PCOS group was significantly lower than that of the control group and the traditional Chinese medicine group;there was no significant difference in the above indicators between the control group and the traditional Chinese medicine group.[Conclusions]The endometrial receptivity of PCOS rats was decreased;Jiawei Buzhong Yiqi Decoction can improve the endometrial receptivity of PCOS rats by increasing the expression of LIF and integrinαvβ3 in the endometrium.

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.

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.

Analysis of mechanism of Buzhong Yiqi Decoction in treating senile functional constipation via network pharmacology

Objective:To explore the molecular mechanism of buzhong yiqi decoction in the treatment of senile functional constipation based on network pharmacology.Methods:Chemical compositions and selected targets related to the eight traditional Chinese medicine herbs were searched through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Through GeneCards database and OMIM database,disease targets of senile functional constipation were searched.R language was used to screen the common targets between drugs and disease,and then the interaction network diagram of the targets was constructed by String.Cytoscape3.7.0 was applied to construct the traditional Chinese medicines-chemical compositions-disease targets network.GO enrichment analysis and KEGG enrichment analysis of the targets were based on DAVID.Results:Five main chemical compositions including quercetin,kaempferol,nobiletin,naringenin and formononetin were screened,and five key targets including PTGS2,ESR1,AR,NOS2 and PPARG were identified.622 GO functional entries and 125 pathways were yielded by gene enrichment analysis.Conclusion:Buzhong yiqi decoction may play the role of anti-inflammatory and anti-oxidation through multi-component,multi-target and multi-channel,so as to improve senile functional constipation.

Yiqi Fusheng Decoction reverses cisplatin resistance in colorectal cancer by down-regulating HIF-1αand p-ERK1/2

Objective:To explore the reversing resistance mechanisms of Yiqi Fusheng Decoction(YQFS)on human multidrug-resistant colorectal cancer cell HT-29/DDP.Methods:Colorectal cancer cell HT-29/DDP was treated with YQFS for 48h and MTT assay was used to detect the effect of HT-29/DDP cells on the sensitivity of chemotherapeutic drugs.Cell apoptosis was measured by flow cytometry.The effects of YQFS on the expression of HIF-1α,ERK1/2 and p-ERK1/2 in HT-29/DDP cells were detected by Western blot.Results:High concentration and low concentration YQFS groups can significantly inhibit the proliferation of HT-29/DPP cells compared with the control group(P<0.01).And the high concentration YQFS group has a more significant inhibitory effect on cell proliferation.Compared with the cisplatin group,the proliferation of HT-29/DDP cells in YQFS and cisplatin group decreased dramatically and cell apoptosis increased significantly(P<0.01).Moreover,the expressions of HIF-1αand p-ERK were reduced in the YQFS group compared with the cisplatin group(P<0.01).Conclusion:YQFS can increase the sensitivity of multidrug-resistant colorectal cancer cells to chemotherapeutic drugs and promote cell apoptosis by down-regulating the expressions of HIF-1αand p-ERK1/2.

Effect of Huoxue Huayu Lishui Decoction on P65 and TAK1 of acute soft tissue injury in rats

Objective:To explore the mechanism of the action of Huoxue Huayu Lishui prescription on acute ankle joint injury.Methods:Forty-eight SPF rats were randomly divided into blank group,model group,Shujin Huoluo capsule group,low,medium and high dose groups for promoting blood circulation and removing blood stasis.The blank group was not modeled,and the other groups were modeled.Each group of 8 animals,the Shujin Huoluo capsule group was given 0.2g/ml mixed liquid by gavage,and the low,medium and high blood circulation and blood stasis Lishui prescription group was given 1.03g/ml,2.06g/ml,4.12g/ml decoction For the stomach,the normal group was given 1.5ml/100g,once a day for 1 week.The expression of NF-κB P65 and transforming growth factor kinase 1(TAK1)protein in the soft tissue around the ankle joint of rats was detected by sports protein immunoblotting method,and the mRNA expression of NF-κB P65 and TAK1 was detected by PCR technology.Results:One day after modeling,the expressions of P65 and TAK1 mRNA and protein in the model group,the positive drug group,and low,medium and high doses of Huoxue Huayu Lishui Recipe were significantly different from those of the blank control group(P<0.05).After taking the medicine for 7 days,compared with the model group,the expressions of P65 and TAK1 mRNA and protein in the Shujin Huoluo capsule group and the low,medium and high dose Huoxue Huayu Lishui Recipe group were all decreased(P<0.05).After 7 days of taking the medicine,compared with the Shujin Huoxue Capsule group,there was no difference in P65 protein in the low-dose Huoxue Huayu Lishui Recipe group.The expression of P65 protein in the middle and high groups and the Shujin Huoxue Capsule group were all decreased(P<0.05).Compared with the Shujin Huoxue Capsule group,the expressions of TAK1 protein,P65 and TAK1 mRNA in the low,medium,and high groups and the Shujin Huoxue Capsule group were all decreased(P<0.05).The results suggest that Huoxue Huayu Lishui Recipe can inhibit the expression of NF-κB P65 and TAK1 protein in ankle joint injury.Conclusion:Huoxue Huayu Lishui prescription may regulate the expression of NF-κB P65 and TAK1 in ankle joint injury of NF-κB rats,so as to improve the clinical symptoms of local swelling and pain in the ankle joint.