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.

Jianpi Fuzheng Decoction in the Treatment of Gastric Cancer-Related Fatigue

Objective:To observe the clinical effects of Jianpi Fuzheng Decoction in patients with gastric cancer and cancer-related fatigue(CRF).Methods:Using the random number table method as a reference,68 cases of gastric CRF were randomly divided into two groups.One group served as the control group and received basic treatment,while the other was the observation group.The observation group,in addition to the control group’s treatment,received Jianpi Fuzheng Decoction.The clinical treatment effectiveness,fatigue scores,immune function indicators,and treatment safety were compared between the two groups.Results:The total clinical treatment effectiveness of the observation group and the improvement in immune function indicators after treatment were higher than those of the control group.The fatigue score after treatment was lower in the observation group than in the control group(P<0.05).No serious adverse reactions occurred during the treatment in either group.Conclusion:Jianpi Fuzheng Decoction can enhance the clinical treatment effectiveness for gastric cancer patients with CRF.It facilitates the acceleration of fatigue symptom improvement and immune function enhancement.The medication’s safety is guaranteed,making it worthy of promotion.

Clinical Thoughts and Cases of Jianpi Yishen Sechang Decoction Combined with Acupuncture in the Treatment of Functional Diarrhea

Functional diarrhea(FDr)accounts for a relatively high proportion of digestive diseases.It is an infection that is not accompanied by abdominal pain and shows negative results in laboratory tests for bacteria and viruses.The main symptoms are persistent or recurrent discharge of watery and soft stools.The course of the disease is prolonged and recurring,and the treatment cost is higher and greatly affects the patient’s daily life.The incidence rate has a gradual increase in the trend.Its pathogenesis is complex where Western medicine is mostly used in symptomatic drug treatment.The treatment can be fast-acting and effective in relieving diarrhea.However,the long-term use of Western medicine poses a high risk in terms of side effects and a high chance of recurring upon stopping medication.At the same time,some diarrhea patients show the existence of drug-resistant strains of bacteria,and the overall efficacy of the drug is limited.Chinese medicine is mild and able to provide excellent treatment of diarrhea.With its lower price and cost,most families can afford it.Fengliang Tian,director of traditional Chinese medicine,implemented the“needle and medicine”method,which combines medicine and acupuncture,involving the usage of Jianpi Yishen Sechang Decoction and acupuncture in the treatment of functional diarrhea.The method has a low price,fewer side effects,is easy to accept,and can significantly reduce the recurrence rate with high efficacy.The study would like to share the clinical thinking and cases as follows to provide ideas and methods for the treatment of functional diarrhea by traditional Chinese medicine.

Jianpi Qingchang decoction alleviates ulcerative colitis by inhibiting nuclear factor-κB activation

To investigate the therapeutic effect of Jianpi Qingchang decoction (JPQCD) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice.METHODSC57BL/c mice were injected intragastrically with 5% DSS instead of drinking water for 7 d, and their body weight, diarrhea severity and fecal bleeding were monitored, while the mice in the control group were treated with standard drinking water, without DSS. After 7 d, the DSS drinking water was changed to normal water and the DSS group continued with DSS water. The control and DSS groups were given normal saline by intragastric injection. The 5-aminosalicylic acid (5-ASA) group was treated orally with 5-ASA at a dose of 100 mg/kg daily. The JPQCD group was treated orally with JPQCD at a dose of 17.1 g/kg daily. On day 14, the colon length was measured, the colorectal histopathological damage score was assessed, and protein levels of interleukin (IL)-1β, IL-8 and tumor necrosis factor-alpha (TNF-α) in colon supernatants were measured by enzyme-linked immunosorbent assay. mRNA expression of IL-1β, IL-8, TNF-α and nuclear factor-kappa B (NF-κB) was detected by real-time quantitative polymerase chain reaction. Western blotting was used to detect the protein expression of NF-κB and inhibitor of kappa B.RESULTSAcute inflammation occurred in the mice administered DSS, including the symptoms of losing body weight, loose feces/watery diarrhea and presence of fecal blood; all these symptoms worsened at 7 d. The colons of mice treated with DSS were assessed by histological examination, and the results confirmed that acute inflammation had occurred, as evidenced by loss of colonic mucosa and chronic inflammatory cell infiltration, and these features extended into the deeper layer of the colon walls. The expression levels of IL-1β, IL-8 and TNF-α in the DSS group were higher than those in the control group (P < 0.05), and the expression levels of IL-1β, IL-8 and TNF-α in the JPQCD and 5-ASA groups were lower than those in the DSS group after treating with JPQCD and 5-ASA. Comparing with the DSS group, the mRNA level of IL-1β, IL-8, TNF-α and NF-κB was significantly reduced by 5-ASA and JPQCD. The difference between JPQCD and 5-ASA groups was not statistically significant (P > 0.05). Comparing with the DSS group, due to using JPQCD and 5-ASA, significant suppression of activation in DSS-induced NF-κB and increased phosphorylation of IκB in mice with experimental colitis occurred (P < 0.05). The difference between the JPQCD group and the 5-ASA group was not statistically significant (P > 0.05).CONCLUSIONActivation of the NF-κB signaling pathway is inhibited by JPQCD, which shows the potential mechanism by which JPQCD treats UC.

Jianpi Qingchang decoction regulates intestinal motility of dextran sulfate sodium-induced colitis through reducing autophagy of interstitial cells of Cajal

AIM To investigate the underlying effect of Jianpi Qingchang decoction(JQD) regulating intestinal motility of dextran sulfate sodium(DSS)-induced colitis in mice. METHODS C57BL/6 mice were randomly divided into four groups: the control group, the DSS group, the JQD group, and the 5-aminosalicylic acid group. Except for the control group, colitis was induced in other groups by giving distilled water containing 5% DSS. Seven days after modeling, the mice were administered corresponding drugs intragastrically. The mice were sacrificed on the 15^(th) day. The disease activity index, macroscopic and histopathologic lesions, and ultrastructure of colon interstitial cells of Cajal(ICC) were observed. The levels of tumor necrosis factor-alpha(TNF-α), interleukin(IL)-1β, IL-10 and interferon gamma(IFN-γ), the expression of nuclear factor-kappa B(NF-κB) p65, c-kit, microtubule-associated protein 1 light chain 3(LC3-Ⅱ) and Beclin-l m RNA, and the colonic smooth muscle tension were assessed. RESULTS Acute inflammation occurred in the mice administered DSS. Compared with the control group, the levels of IL-1β, TNF-α, IL-10 and IFN-γ, the expression of LC3-Ⅱ, Beclin-1 and NF-κB p65 m RNA, and the contractile frequency increased(P < 0.05), the expression of c-kit m RNA and the colonic smooth muscle contractile amplitude decreased in the DSS group(P < 0.05). Compared with the DSS group, the levels of IL-10 and IFN-γ, the expression of c-kit m RNA, and the colonic smooth muscle contractile amplitude increased(P < 0.05), the levels of TNF-α and IL-1β, the expression of LC3-Ⅱ, Beclin-1 and NF-κB p65 m RNA, and the contractile frequency decreased in the JQD group(P < 0.05).CONCLUSION JQD can regulate the intestinal motility of DSS-induced colitis in mice through suppressing intestinal inflammatory cascade reaction, reducing autophagy of ICC, and regulating the network path of ICC/smooth muscle cells.

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.

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.

Jianpi Qingchang Bushen decoction improves inflammatory response and metabolic bone disorder in inflammatory bowel disease-induced bone loss

BACKGROUND Bone loss and osteoporosis are commonly described as extra-intestinal manifestations of inflammatory bowel disease(IBD).Jianpi Qingchang Bushen decoction(JQBD)is a prescription used in clinical practice.However,further studies are needed to determine whether JQBD regulates the receptor activator of nuclear factor kappa B(NF-κB)(RANK)/receptor activator of NF-κB ligand(RANKL)/osteoprotegerin(OPG)pathways and could play a role in treating IBD-induced bone loss.AIM To evaluate the therapeutic effect of JQBD in IBD-induced bone loss and explore the underlying mechanisms.METHODS An IBD-induced bone loss model was constructed by feeding 126-to-8-wk-old interleukin-10(IL-10)-knockout mice with piroxicam for 10 d.The mice were randomly divided into model and JQBD groups.We used wild-type mice as a control.The JQBD group was administered the JQBD suspension for 2 wk by gavage,while the control and model groups were given normal saline at the corresponding time points.All mice were killed after the intervention.The effect of JQBD on body weight,disease activity index(DAI),and colon length was analyzed.Histopathological examination,colon ultrastructure observation,and micro-computed tomographic scanning of the lumbar vertebrae were performed.The gene expression of NF-κB,tumor necrosis factor-α(TNF-α),IL-1β,IL-6,and IL-8 in the colon was evaluated by real-time polymerase chain reaction.Colon samples were assessed by Western blot for the expression of RANKL,OPG,RANK,and NF-κB proteins.RESULTS The model group lost body weight,had a shorter colon,and showed a dramatic increase in DAI score,whereas JQBD had protective and therapeutic effects.Treatment with JQBD significantly improved inflammatory cell infiltration and reduced crypt abscess and ulcer formation.Threedimensional imaging of the vertebral centrum in the model group revealed a lower bone mass,loose trabeculae,and“rod-shaped”changes in the structure compared to the control group and JQBD groups.The bone volume/total volume ratio and bone mineral density were significantly lower in the model group than in the control group.JQBD intervention downregulated the NF-κB,TNF-α,IL-1β,IL-6,and IL-8 m RNA expression levels.The RANKL and OPG protein levels were also improved.CONCLUSION JQBD reduces inflammation of the colonic mucosa and inhibits activation of the RANK/RANKL/OPG signaling pathway,thereby reducing osteoclast activation and bone resorption and improving bone metabolism.

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.

Clinical application of Bushen Jianpi Gutai Decoction in threatened abortion

Objective:To discuss the clinical application of the"seven,five and three"odd-numbered law theory and analyze the effect on serum sex hormone level.Methods:A total of 100 patients with early threatened abortion admitted from January 2021 to October 2021 were randomly divided into study group and control group,with 50 patients in each group.Patients in the control group were treated with dydrogesterone tablets,while patients in the study group were treated with Bushen JianpiGutai Decoction combined with dydrogesterone tablets.Clinical efficacy and progesterone level before and after treatment were observed and compared between the two groups,as well as clinical symptom relief time of the two groups,including hemostasis time,abdominal pain relief time and lumbar acid relief time,and sex hormone level of the two groups were observed and compared.Results:The clinical efficacy was significantly better than control patients(P<0.05),no significant difference in progesterone level comparison before treatment(P>0.05),significantly better than control patients(P<0.05),hemostasis,abdominal pain remission and waist acid remission were significantly shorter than control patients(P<0.05),and both significantly better sex hormone levels after treatment(P<0.05).Conclusion:Traditional Chinese medicine has certain advantages in the treatment of threatened abortion,odd-numbered law theoryguidesthe regulation of Yin and Yang in the female menstrual cycle and reproductive function is mainly the regular change of Yin and Yang.Under the guidance of"seven,five,three"odd-numbered law theoryof Traditional Chinese medicine master Xia Guicheng,master the key date and the best time of its transformation,regulate Yin and Yang in the female body,to prevent the occurrence and development of menstrual diseases and adverse childbirth.Bushen Jianpi Gutai decoction can effectively treat threatened abortion,significantly improve the clinical symptoms,improve the level of serum sex hormone,worthy of clinical promotion.

Exploring the molecular biological mechanism of Shugan Jianpi Decoction in the treatment of depression-related breast cancer based on network pharmacology

Objective:To explore the molecular biological mechanism of Shugan Jianpi Decoction in treating depression-related breast cancer based on network pharmacology.Methods:The active compounds of Shugan Jianpi Decoction were explored to obtain their drug targets,and the venny network,"TCM-component-target"network,PPI network,"pathway-gene"network,GO and KEGG enrichment results were constructed using relevant softwares.Results:A total of 121 active ingredients,250 genes,2357 GO functions and 184 KEGG pathways were obtained.Conclusion:The active ingredients of Shugan Jianpi Decoction are quercetinll、kaempferol、luteolin、naringenin.The key targets are MAPK1,MAPK3,RELA,and AKT1.GO functions include cellular response to hormone stimulus、cellular response to lipid、cellular response to oxidative stress and so on.KEGG mainly involves PI3K-Akt,microRNAs,and FoxO signaling pathways.This study preliminarily explores the molecular biological mechanism of Shugan Jianpi Decoction in the treatment of depression-related breast cancer,and speculates that it mainly acts by arresting the cell cycle,inhibiting cancer cell proliferation,mediating cancer cell apoptosis,and preventing its recurrence and metastasis,which provides new evidence and new direction for subsequent clinical application and experimental research.

Jianpi Qingchang Decoction-containing serum regulates the autophagy ofinterstitial cells

Objective： To investigate the effects of Jianpi Qingchang Decoction-containing serum （JQD-CS） on interstitial cells ofCajal （ICCs） autophagy and cell cycle arrest in vitro. Methods： ICCs were collected from the small intestines of miceand analyzed using an anti-c-Kit antibody. ICCs were divided into five groups： the blank group, the rapamycin group （anautophagy inducer）, the 5% （rapamycin ＋ 5% JQD-CS）, the 20% （rapamycin ＋ 20% JQD-CS） JQD-CS groups, and the3-Methyladenine （3-MA） group （rapamycin ＋ 3-MA; positive control）. Transmission electron microscopy was used toobserve the ultrastructure of ICCs. Western blotting was used to detect the expression of microtubule-associated protein1 light chain 3 （LC3-II）, Beclin-1, phosphatidylinositol 3-kinase （PI3K）, p-PI3K, protein kinase B （AKt）, p-AKt,mammalian target of rapamycin （mTOR）, and p-mTOR. Ca2＋ current was examined by patch-clamp experiments. Cellcycle was detected by flow cytometry. Results： Unlike in the rapamycin group, the ICC structures were more integratedand a lower number of autophagic vacuoles were observed in the 20% JQD-CS group. Moreover, the expression ofLC3-II and Beclin-1 decreased, the expression of c-Kit, p-PI3K, p-AKt increased, the maximum current density valuedecreased, and the number of cells in the G1 phase increased while those in the G2/M phase decreased, with the additionof 20% JQD-CS. Conclusion： JQD-CS can antagonize rapamycin-induced autophagy in ICCs in vitro by promoting thephosphorylation of PI3K/AKt pathway, inhibiting Ca2 ＋ inflow, and regulating the cell cycle.

Effect of Acupuncture and Jianpi Bushen Decoction on Ovarian Function and Metabolic Disorders in Patients with PCOS

Objective:To study the effects of acupuncture combined with Jianpi Bushen Decoction on ovarian function and metabolic disorders in patients with polycystic ovary syndrome(PCOS).Methods:A total of 100 PCOS patients admitted in our hospital from October 2018-January 2020 were selected,and the patients were divided into the Jianpi Bushen Decoction group and the combined group with 50 patients each according to a completely random method.The patients in the Jianpi Bushen Decoction group were given Jianpi Bushen Decoction;the combined group was given acupuncture on the basis of the Jianpi Bushen Decoction group.Detection of follicle stimulating hormone(FSH),testosterone(T),pituitary prolactin(PRL),estradiol(E2),fasting insulin(FIN),fasting blood glucose(FBG),insulin resistance index(HOMA-IR),triglyceride Ester(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),endometrial thickness,ovarian volume,number of ovarian sinus follicles,C-reactive protein(CRP),procalcitonin(PCT).Statistical treatment is effective.Results:After treatment,FSH,T,PRL,FIN,FBG,HOMA-IR,TG,TC and LDL-C were lower in Jianpi Bushen Decoction group,and E2 and HDL-C levels were higher than Jianpi Bushen Decoction group(P<0.05).The endometrial thickness of the combined group was higher than that of Jianpi Bushen Decoction group,and the ovarian volume and the number of ovarian sinus follicles were lower than that of Jianpi Bushen Decoction group(P<0.05).The levels of CRP and PCT in the combination group were lower than those in the Jianpi Bushen Decoction group(P<0.05).The total effective rate of patients in combination group was higher than that in Jianpi Bushen Decoction group(P<0.05).Conclusion:Acupuncture combined with Jianpi Bushen Decoction has significant therapeutic effects on patients with PCOS,effectively improves patients'ovarian function,improves endocrine and metabolic disorders,and reduces inflammatory reactions,which deserves clinical promotion.

Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase

ObjectiveTo provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction(JP)and to explore its mechanism of anti-cancer cachexia.MethodsA mouse model of colon cancer(CT26)-induced cancer cachexia(CC)was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate(MPA).Thirty-six mice were equally divided into 6 groups:normal control,CC,MPA(100 mg·kg^(−1)·d^(−1)),MPA+low-dose(20 mg·kg^(−1)·d^(−1))JP(L-JP),MPA+medium-dose(30 mg·kg^(−1)·d^(−1))JP(M-JP),and MPA+high-dose(40 mg·kg^(−1)·d^(−1))JP(H-JP)groups.After successful modeling,the mice were administered by gavage for 11 d.The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation.The liver,heart,spleen,lung,kidney,tumor and gastrocnemius muscle of mice were collected and weighed.The pathological changes of the tumor was observed,and the cross-sectional area of the gastrocnemius muscle was calculated.The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot.In addition,an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy.In vitro experiments were divided into control,model,and JP serum groups.After 2-d administration,microscopic photographs were taken and myotube diameters were calculated.Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase.ResultsJP combined with MPA restored tumor-induced weight loss(P<0.05,vs.CC)and muscle fiber size(P<0.01,vs.CC).Mechanistically,JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo(P<0.05,vs.CC).In addition,JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation(P<0.05 or P<0.01 vs.model group)in C2C12 myotubes treated with dexamethasone in vitro.ConclusionsAdministration of JP combined with MPA restores tumor-induced cachexia conditions.In addition,the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis(E3 ubiquitinase system).

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin(Heart)-Pi(Spleen)Deficiency Syndrome:A Multi-centre Randomized Controlled Study

Objective:To evaluate the efficacy and safety of Jianpi Jieyu Decoction(JJD)for treating patients with mild-to-moderate depression of Xin(Heart)-Pi(Spleen)deficiency(XPD)syndrome.Methods:In this multi-center,randomized,controlled study,140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019.They were randomly divided into JJD group and paroxetine group by using a random number table,with 70 cases in each group.The patients in the JJD group were given JJD one dose per day(twice daily at morning and evening,100 m L each time),and the patients in the paroxetine group were given paroxetine(10 mg/d in week 1;20 mg/d in weeks 2-6),both orally administration for a total of 6 weeks.The primary outcome was the change of 17-item Hamilton Depression Rating Scale(HAMD-17)score at week 6 from baseline.The secondary outcomes included the Hamilton Anxiety Scale(HAMA)score,Traditional Chinese Medicine Symptom Scale(TCMSS),and Clinlcal Global Impression(CGI)scores at the 2nd,4th,and 6th weekends of treatment,HAMD-17 response(defined as a reduction in score of>50%)and HAMD-17 remission(defined as a score of 7)at the end of the 6th week of treatment.Adverse events(AEs)were also recorded.Results:From baseline to week 6,the HAMD-17 scores decreased 10.2±4.0 and 9.1±4.9 points in the JJD and paroxetine groups,respectively(P=0.689).The HAMD-17 response occurred in 60%of patients in the JJD group and in 50%of those in the paroxetine group(P=0.292);HAMD-17 remission occurred in 45.7%and 30%of patients,respectively(P=0.128).The differences of CGI scores at the 6th week were not statistically significant(P>0.05).There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week(P=0.001 and P=0.014).The HAMA scores declined 8.1±3.0 and 6.9±4.3 points from baseline to week 6 in the JJD and paroxetine groups,respectively(P=0.905 between groups).At 4th week of treatment,there was a significant difference in HAMA between the two groups(P=0.037).TCMSS decreased 11.4±5.1,and 10.1±6.8 points in the JJD and paroxetine groups,respectively(P=0.080 between groups).At the 6th week,the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group(7.14%vs.22.86%,P<0.05).Conclusion:Compared with paroxetine,JJD was associated with a significantly lower incidence of AEs in patients with mild-tomoderate depression of XPD syndrome,with no difference in efficacy at 6 weeks.(Trial registration No.Chi CTR2000040922).

Structural Shifts of Gut Flora in Rat Acute Alcoholic Liver Injury and Jianpi Huoxue Decoction's(健脾活血汤)Effect Displayed by ERIC-PCR Fingerprint

Objective： To study the structural shifts of gut flora in rats with acute alcoholic liver injury （AALI）, and the effect of Jianpi Huoxue Decoction （健脾活血汤, JPHXD） on the gut flora. Methods： Thirty-six Sprague- Dawley rats were randomly allocated to the control, AALI and JPHXD groups equally. The rats in the control group were given water and those in AALI and JPHXD groups were given ethanol by intragastric gavage for 5 days, while rats in the JPHXD group were administered JPHXD simultaneously. The blood and liver tissue were collected at the end of the experiment. The activities of serum alkaline aminotransferase （ALT）, aspartate aminotransferase （AST）, hepatic γ/-glutamyitranspetidase （γ-GT） and hepatic tdglyceride （TG） levels were determined. Plasma endotoxin level in the portal vein was measured. Pathological changes of liver tissues were determined by hematoxylin and Eosin （HE） staining and oil red O staining. The total DNA of gut flora were extracted from fecal samples by Bead-beating method and determined by ERIC-PCR fingerprint method. The similarity cluster analysis and principal component analysis were performed to analyze the ERIC-PCR fingerprint respectively. Results： In the AALI group, the ratio of liver/body weight, activities of ALT, AST and hepatic γ-GT, amount of hepatic TG were elevated significantly compared with those in the control group （all P〈0.01）. JPHXD decreased the ratio, activities of ALT, AST, γ-GT and TG significantly compared with those in the AALI group （P〈0.05 or P〈0.01）. HE and oil red O staining showed that fat deposited markedly in liver tissue, while JPHXD alleviated pathological changes markedly. Plasma LPS level in rat portal vein in the AALI group increased significantly （P〈0.01）, but it was decreased significantly in the JPHXD group （P〈0.01）. The cluster analysis and principal component analysis of ERIC-PCR fingerprint showed that gut flora in the hALl group changed markedly, and JPHXD could recover gut flora to some extent. Conclusion： The structure of gut flora shifted markedly during acute alcoholic liver injury, JPHXD had prevention effect through the modification of gut flora.

Intervention Effects of Jianpi Liqi Huoxue Decoction (健脾理气活血汤) on Lipid Peroxidative Liver Injury Induced by Alcohol

Objective： To study the intervention effects of Jianpi Liqi Huoxue Decoction （健脾理气活血汤, JLHD） on lipid peroxidative liver injury induced by alcohol. Methods： The rat alcoholic model of liver disease （ALD） induced by Lieber-DeCarli liquid diet was established. Thirty-two male SD rats were randomly divided into 4 groups ： the normal group （ n = 5）, the control group （ n = 9）, the model group （ n = 9） and the JLHD group （ n =9）. From the 4th week after modeling, the rats were given JLHD or distilled water by gastrogavage respectively, and the samples of blood and liver tissues were taken out from the rats for determination by the end of the 8th week. The hepatic pathological changes were observed with HE staining; the liver injury related indices, including activity of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum, γ-glutamyl transpeptidase （γ-GT） activity and triglyceride （TG） content in liver tissues, as well as the lipid peroxidation related indices, including malonaldehyde （MDA） content and nitric oxide synthase （NOS） activity in liver tissue, serum Fe^2＋ level, and the anti-peroxidation capacity related indices, including superoxide dismutase （SOD） activity, glutathion （GSH） content and reactive oxygen species （anti- ROS） activity in liver tissues were determined. Results： （ 1 ） There were obvious figures of fatty degeneration and inflammatory infiltration in liver tissues of the model group. As compared with the control group, in the model group, the activity of ALT and AST, and Fe^2＋ content in serum, γ-GT and NOS activity, TG and MDA content in liver tissues were significantly higher （ P〈0. 01 ）, while the activity of SOD, GSH and anti-ROS in liver tissues were significantly lower （P〈0.01）. （2） The fatty degeneration and inflammatory infiltration of liver tissues in the JLHD group were significantly lessen as compared with those in the model group; and the abnormalities of all the indexes revealed in the model rats were restored to certain extent in the JLHD group, and especially significant were the levels of ALT activity, MDA content and Fe^2＋ , which were nearly normal. Conclusion： JLHD has significant effects against alcoholic liver injury, the acting mechanism of which is likely to be related with its anti-lipid peroxidative effect.

Therapeutic Effect of Jianpi Decoction Combined with Chemotherapy on Postoperative Treatment of Colorectal Cancer: A Systematic Review and Meta-analysis

Objective:The purpose of this systematic review is to assess the therapeutic effect of Jianpi decoctions in Chinese herbal medicines(CHM)combined with chemotherapy on the postoperative treatment of colorectal cancer.Methods:Literatures were obtained from Wanfang database,CNKI,Pub Med,Cqvip,MEDLINE,Cochrane,CBM,and Springer LINK as well as other conference papers and theses.The search included all documents in English or Chinese published before September 2018.We selected randomized controlled trials based on specific criteria and the most important criteria were that Jianpi decoction should be applied in combination with chemotherapy on the postoperative treatment of colorectal cancer.Results:Publications in eight electronic databases were extensively searched and 20 trials were included for analysis eventually.A total of 1652 patients in total were enrolled in these studies.Among them,879 patients received CHM and Western medicine combination therapy and another 773 participants only got Western medicine therapy.Compared with those patients receiving Western medicine alone,the survival rate of 1-year(odds ratio[OR]=2.35,95%confidence limit[Cl]=1.30–4.28,P<0.05),3-year(OR=2.02,95%Cl=1.49–2.73,P<0.001),and 5-year survival rate(OR=2.32,95%Cl=1.56–3.45,P<0.001)of patients in the group of Jianpi decoctions in CHM and chemotherapy combination has significantly increased.Moreover,results also showed positive effects on immunoregulation such as CD3^+(OR=0.68,95%confidence interval[CI]=0.52–0.85,P<0.0001),CD4^+/CD8^+(OR=0.77,95%CI=0.29–1.26,P<0.05).Side effects caused by chemotherapy such as nausea(OR=0.35,95%CI=0.25–0.50,P<0.0001)and vomiting(OR=0.32,95%CI=0.22–0.46,P<0.0001),diarrhea(OR=0.42,95%CI=0.30–0.60,P<0.0001),as well as metastasis and recurrence(OR=0.38,95%CI=0.24–0.61,P<0.001)were remarkably reduced.The quality of life(OR=4.40,95%Cl=2.86–6.77,P<0.0001)has been improved.Moreover,there was no statistically significant bias in the overall studies.Conclusion:This systematic review suggests that Jianpi decoction in CHM can reduce the chemotherapy toxicity,enhance the patient's immunity,prolong their survival rate,improve their quality of life as well as prevent metastasis,and recurrence for patients in postoperative treatment of colorectal cancer.

Patients with Metastatic Colorectal Cancer after Failure of Second-Line Treatment May Benefit from Low-Dose Apatinib and S-1 Combined with Jianpi Bushen Jiedu Decoction

Objective: To evaluate the effect and safety of low-dose of apatinib and S-1 combined with Jianpi Bushen Jiedu Decoction(JBJD) in patients with metastatic colorectal cancer(mCRC) who have failed second or above lines treatment, in order to provide more treatment option for mCRC patients by integrated medicine. Methods: Thirteen patients were selected from a single-arm, open-label clinical study from April 2019 to September 2020. The patients were treated with low-dose apatinib(250 mg, once a day) and S-1(20 mg, twice a day) combined with JBJD for at least one cycle and were followed up to August 2021. The primary endpoint was disease progression-free survival(PFS). Disease control rate(DCR), objective response rate(ORR), and overall survival(OS) of patients were observed as the secondary endpoints. Adverse events were recorded as well. Results: The average age of the 13 patients was 56.5±13.0 years and 76.9% were male. The median PFS and median OS were 4.6 and 8.3 months, respectively. The ORR was 7.7%(1/13) while the DCR was 61.5%(8/13). The common adverse events were hypertension, proteinuria, elevated transaminase, and thrombocytopenia. One patient experienced thrombocytopenia of grade 3. Conclusions: Patients with mCRC after failure of the second or above lines of treatment may potentially benefit from the treatment of low-dose apatinib and S-1 combined with JBJD because of its similar effect as the standard dose of target therapy and relatively better safety.(Registration No. ChiCTR1900022673)