Hepatic metabolomics combined with network pharmacology to reveal the correlation between the anti-depression effect and nourishing blood effect of Angelicae Sinensis Radix / 中国天然药物

Angelicae Sinensis Radix (AS) is reproted to exert anti-depression effect (ADE) and nourishing blood effect (NBE) in a rat model of depression. The correlation between the two therapeutic effects and its underlying mechanisms deserves further study. The current study is designed to explore the underlying mechanisms of correlation between the ADE and NBE of AS based on hepatic metabonomics, network pharmacology and molecular docking. According to metabolomics analysis, 30 metabolites involved in 11 metabolic pathways were identified as the potential metabolites for depression. Furthermore, principal component analysis and correlation analysis showed that glutathione, sphinganine, and ornithine were related to pharmacodynamics indicators including behavioral indicators and hematological indicators, indicating that metabolic pathways such as sphingolipid metabolism were involved in the ADE and NBE of AS. Then, a target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis, where a total of 107 pathways were collected. Moreover, 37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer (UPLC-Triple-TOF/MS) in AS extract that passed the filtering criteria were used for network pharmacology, where 46 targets were associated with the ADE and NBE of AS. Pathway enrichment analysis further indicated the involvement of sphingolipid metabolism in the ADE and NBE of AS. Molecular docking analysis indciated that E-ligustilide in AS extract exhibited strong binding activity with target proteins (PIK3CA and PIK3CD) in sphingolipid metabolism. Further analysis by Western blot verified that AS regulated the expression of PIK3CA and PIK3CD on sphingolipid metabolism. Our results demonstrated that sphingolipid metabolic pathway was the core mechanism of the correlation between the ADE and NBE of AS.

Effect of Modified Shiquan Dabutang on Inflammatory and Bone Metabolism Indexes in Elderly Patients with Osteoporotic Intertrochanteric Fractures Due to Qi and Blood Deficiency / 中国实验方剂学杂志

Objective:To explore the application value of modified Shiquan Dabutang in the treatment of elderly patients with osteoporotic intertrochanteric fractures （OIFs） due to Qi and blood deficiency by observing its impacts on inflammatory and bone metabolism indexes. Method:Ninety-eight elderly patients admitted to our hospital for OIFs of Qi and blood deficiency syndrome from April 2018 to April 2020 were randomized into an observation group （<italic>n</italic>=49） and a control group （<italic>n</italic>=49）. Following the proximal femoral nail antirotation （PFNA） fixation， patients in the control group were treated with Guipiwan， while those in the observation group received the modified Shiquan Dabutang. The clinical efficacy， inflammatory and bone metabolism indexes， and complications were compared between the two groups after four weeks of treatment. Result:The levels of such serum indexes as fibroblast growth factor-2 （FGF-2）， osteoprotegerin （OPG）， transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， <italic>β</italic>-endorphin （<italic>β</italic>-EP）， bone-specific alkaline phosphatase （BALP）， and osteocalcin （BGP） in the observation group after treatment were significantly elevated as compared with those in the control group （<italic>P</italic><0.05）， whereas the serum tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and <italic>D</italic>-dimer （<italic>D</italic>-D） declined （<italic>P</italic><0.05）. The TCM symptom score in the observation group after treatment was obviously lower than that in the control group， while the Harris Hip Score （HHS） was higher （<italic>P</italic><0.05）. The overall response rate of the observation group was 93.88% （46/49）， higher than 75.51% （37/49） of the control group （<italic>χ²</italic>=6.376， <italic>P</italic><0.05）. The total incidence of incision infection， deep vein thrombosis of lower limbs， and pulmonary infection in the control group was 24.49% （12/49）， significantly higher than 6.12% （3/49） in the observation group （<italic>χ²</italic>=6.607， <italic>P</italic><0.05）. Conclusion:The modified Shiquan Dabutang is able to alleviate inflammation， regulate bone metabolism， promote bone repair， and reduce the incidence of complications in elderly patients with OIFs due to Qi and blood deficiency.

Effect of Modified Bazhentang on Nutritional Status and Immune Function of Gastric Cancer Patients with Neoadjuvant Chemotherapy / 中国实验方剂学杂志

Objective:To observe the effect of modified Bazhentang on the nutritional status and immune function of patients with Qi and blood deficiency syndrome in neoadjuvant chemotherapy （NAC） for gastric cancer. Method:One hundred and ten patients were randomly divided into observation group and control group with 55 cases each. Both groups accepted FOLFOX6 protocol. Patients in control group took Jianpi Shengxue tablets orally， 3 tablets/time， 3 times/day. Patients in observation group received modified Bazhentang， 1 dose/day. The course of treatment was six weeks in both groups. Before and after treatment， scores were graded according to patient generated-subjective global assessment （PG-SGA）， Qi and blood deficiency syndrome， and the Revised Piper Fatigue Scale （PFS-R）. Levels of serum total protein （TB）， albumin （ALB）， prealbumin （PAB）， CD4⁺， CD8⁺， helper T lymphocyte 17 （Th17）， regulatory T cell （Treg）， immunoglobulin G （IgG）， IgM， and IgA were detected before and after therapy. Body mass index （BMI） and fat free mass index （FFMI） were measured before and after treatment. Weight loss was recorded， and the acute or subacute toxicity of anticancer drugs was evaluated. Result:The degree of malnutrition in the observation group was lower than that in the control group （<italic>Z</italic>=2.401，<italic>P</italic><0.01）. The levels of TB， ALB and PAB in the observation group were higher than those in the control group （<italic>P</italic><0.01）. The CD4⁺， Treg and CD4⁺/CD8⁺ levels in the observation group were higher than those in the control group （<italic>P</italic><0.01）. The CD8⁺， Th17 and Th17/Treg levels were lower than those in the control group （<italic>P</italic><0.01）. Besides， the levels of IgM and IgA in the observation group were higher than those in the control group （<italic>P</italic><0.01）. The PG-SGA score and weight loss in the observation group were lower than those in the control group （<italic>P</italic><0.01）. The BMI and FFMI data of the observation group were higher than those of the control group （<italic>P</italic><0.05）. The scores of PFS-R and Qi-blood deficiency syndrome were lower than those of the control group （<italic>P</italic><0.01）. The incidence of nausea and vomiting in the observation group was 45.45% （25/55）， lower than 65.45% （36/55） in the control group （<italic>χ</italic>²=4.452，<italic>P</italic><0.05）. Conclusion:Modified Bazhentang can be used to assist gastric cancer patients with NAC， which can improve nutritional status and immune function， promote immune balance， reduce clinical symptoms and fatigue， and reduce chemotherapy toxicity and side effects， so it is worthy of clinical use.

Effect of Dingkundan in Adjuvant Treatment of Patients with Radiotherapy and Chemotherapy After Endometrial Carcinoma Operation / 中国实验方剂学杂志

Objective:To observe the effect of Dingkundan in adjuvant treatment of clinical symptoms， quality of life， immune function and prognosis of patients with radiotherapy and chemotherapy after endometrial carcinoma （EC） operation. Method:Patients were divided into control group （82 cases） and observation group （86 cases） according to random number table. A total of 75 patients in control group completed the study （4 patients fell off or lose visit， and 3 patients were eliminated）， while 77 patients in observation group completed the study （5 patients fell off or lose visit， and 4 patients were deleted）. After operation， patients got brachytherapy， external pelvic irradiation and chemotherapy. Patients in control group got Bazhenwan， 1 pill/time， 2 times/day， and those in observation group got Dingkundan， 7 g/time， 2 times/day. The course of treatment lasted for 4 months， and long-time follow-up data was recorded. Before treatment， and at the second and fourth month after treatment， deficiency of Qi and blood was scored. Toxic reactions after radiotherapy and chemotherapy were recorded， and incidence rate of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level were compared. And levels of T lymphocyte subsets （CD3⁺， CD4⁺， CD8⁺ and CD4⁺/CD8⁺） were detected， European collaborative quality of life Cancer Core Scale （EORTC QLQ-C30） was evaluated， and expressions of pce125 （CA125）， epididymis protein 4 （HE4）， Dickkopf-related protein-1 （DKK1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9） and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） were tested before and after treatment. The follow-up was made for every three months， and the progression （recurrence/metastasis） of patients was recorded. Result:Scores of deficiency of Qi and blood in observation group were lower than those in control group at the second and fourth week after treatment （<italic>P</italic><0.01）. Incidence rates of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level and incidence rates of bone marrow suppression， gastrointestinal toxicity， neurotoxicity were lower than those in control group （<italic>P</italic><0.05）. Five functional dimensions and overall quality of life score based on EORTC and QLQ-C30 in observation group were higher than those in control group （<italic>P</italic><0.01）， and scores of three symptom dimensions were lower than those in control group （<italic>P</italic><0.01）. Levels of CD3⁺， CD4⁺ and CD4⁺/CD8⁺ were higher than those in the control group （<italic>P</italic><0.01）， and CD8⁺ was lower than those in the control group （<italic>P</italic><0.01）. Levels of CA125， HE4， DKK1， VEGF， MMP-9 and TGF-<italic>β</italic>₁ were lower than those in the control group （<italic>P</italic><0.01）. The disease progression rate in observation group was 18.18% （14/77）， which was lower than 33.33% （25/75） in control group （<italic>χ</italic>²=4.572， <italic>P</italic><0.05）. Conclusion:In adjuvant treatment of patients with radiotherapy and chemotherapy after EC operation， Dingkundan can reduce the symptoms of Qi and blood deficiency syndrome and side effects caused by radiotherapy and chemotherapy， improve the quality of life and immune function， inhibit the expression of tumor markers and tumor growth factor， delay the progression of tumor and improve the prognosis.

Analysis of Effect of Siwutang on Natural Aging Mice Based on Chinmedomics / 中国实验方剂学杂志

Objective: Through metabonomics research methods,the effect of Siwutang on metabolites and metabolic pathways in natural aging mice were observed.The related targets and mechanism of Siwutang intervention in natural aging mice were analyzed. Method: Taking 20-month-old natural aging model mice(equivalent to 60-65 years old of human beings) as the experimental subjects,at the same time,mice aged 3 months were established as the youth group.UPLC-Q-TOF-MS technique was employed to analyze the mouse plasma with mobile phase of acetonitrile(containing 0.1%formic acid)-0.1%formic acid solution for gradient elution and positive ion mode of electrospray ionization,and the metabolic markers were analyzed by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA),and their metabolic pathways were summarized. Result: Siwutang had obvious reversal effect on the expression levels of 16 aging-related metabolites,among which 9 metabolic markers were statistically significant(PConclusion: Siwutang can affect the metabolites in the plasma of 20-month-old natural aging mice,and the metabolic disorder during the aging process of mice can be improved by glutathione metabolism,pyrimidine metabolism,selenium amino acid metabolism and other pathways,and this paper can provide biological information for the study of material basis of this compound for aging.

Correlate Analysis of Qi and Blood Deficiency Syndrome's Principal Components of Chronic Fatigue Syndrome and TCM Syndrome Differentiation / 中国中医药信息杂志

Objective To analyze the relationship of Qi and blood deficiency syndrome's principal components of chronic fatigue syndrome (CFS) and TCM syndrome differentiation. Methods Syndrome principal components of 25 CFS Qi deficiency patients and 23 CFS blood deficiency patients were researched and combined with TCM syndrome differentiation, then their relationship were analyzed. Results There was significantly positive relationship between CFS Qi deficiency syndrome principal component 1 and CFS Qi deficiency syndrome. And there were significantly positive relationships between CFS blood deficiency syndrome principal component l, 2 and CFS blood deficiency syndrome. Conclusion The CFS Qi deficiency syndrome and blood deficiency syndrome's principal components were accord with TCM syndrome differentiation. We could improve the TCM syndrome differentiation's impersonality and nicety, and predigest TCM diagnosis program if we combined two analysis ways.

Correlate Analysis of Blood Deficiency Syndrome’s Principal Components of Chronic Fatigue Syndrome and Mental Health and Quality of Life / 中国中医药信息杂志

Objective To analyse the relationship of blood deficiency syndrome’s principal components of chronic fatigue syndrome (CFS) and mental state and quality of life. Methods 23 cases of CFS blood deficiency syndrome were collected to pick up principal components, and combined with mental state (SCL-90) and quality of life (SF-36). Then, the relationship was analyzed. Results There was significant relationship between CFS blood syndrome principal component 1 and GH, VT and BP in SF-36. And there was significant relationship between CFS blood syndrome principal component 2 and patients’ somatization, obsessive compulsive, interpersonal sensitive, depression, anxiety, hostility and paranoid in SCL-90, and between principal component 1 and somatization. Conclusion There were two principal components in CFS blood deficiency syndrome, one influenced patients’ quality of life, the other influenced their mental state.

Effect of Siwu Decoction on Liver Mitochondrial Proteome of Blood Deficiency Model Rats / 中医杂志

Objective To observe the mechanism of Siwu Decoction (Decoction of four ingredients) on blood deficiency syndrome.Methods Wistar rats were randomized into 3 groups: model group, treatment group, and normal group, 6 ones in each. Rats of the model group and the treatment group were injected 2% acetylphenylhydrazine (APH) saline subcutaneously on the first, forth and seventh day. From the forth day, the model group was treated with saline by gavage, the treatment group was treated with Siwu Decoction by gavage, and the normal group was treated with saline for 7 days in succession. Then the amount of peripheral blood cells, wet weight of liver and spleen were detected. Liver mitochondrial proteome of all rats were extracted. Proteomic technology was used to measure the regulated proteins by Siwu Decoction.Results In the model group, the rats had decreased general status significantly such as pale, enlarged liver and spleen, lowered red blood cells (RBC) and hemoglobin (HGB), increased white blood cells (WBC) and reticulocyte (RCT) (P