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    2017 Year 23 Vol. 6 Issue

      OriginalPaper

    • Jiao Guo
      2017, 23(6): 403-409. DOI: 10.1007/s11655-017-2811-3
      Abstract:Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settings. However, increasing of the disease incidence, lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattern of the single disease, single target therapy, that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine (WM). On the basis of the combination of the advantages of integrated Chinese medicine (CM) and WM, with unified understanding of such diseases, the new concept of glucolipid metabolic disease (GLMD) is introduced. In this new concept, disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD. The key points of pathology included dysfunction of neuronal-endocrine-immune system, insulin resistance, oxidative stress, inflammation and intestinal flora imbalance. In the core pathogenic perspective of CM, it can be explained as "Gan (Liver) Shi Shu Xie" (dysfunction of Gan in metabolism and emotion regulation) that will lead to the occurence/production of endogenous dampness and phlegm, blood stasis and turbid. This leads to the new concept of "Liver-based regulatory system for metabolic homeostasis" to be introduced further. The comprehensive prevention and control strategy "Tiao Gan Qi Shu Hua Zhuo" (modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness). Its representative formula Fufang Zhenzhu Tiaozhi Capsule (复方贞术调脂胶囊) is innovated under such rationales. Comment for some commonly-used CM GLMD therapeutic drugs was presented. High-level evidence-based and epidemiological and mechanism studies should be carried out to further interpret and explain of the scientific connotation of GLMD.  
      Keywords:glucolipid metabolic disease;liver-based regulatory system for metabolic homeostasis;Tiao Gan (Liver) Qi Shu Hua Zhuo (modulating Gan;trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness);Chinese Medicine   
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      Published:2021-08-27
    • De-wei Ye,Xiang-lu Rong,Ai-min Xu,Jiao Guo
      2017, 23(6): 410-414. DOI: 10.1007/s11655-017-2810-4
      Abstract:Glucolipid metabolic disease (GLMD), a complex of interrelated disorders in glucose and lipid metabolism, has become one of the leading chronic diseases causing public and clinical problem worldwide. As the metabolism of lipid and glucose is a highly coordinated process under both physiological and diseased conditions, the impairment in the signals corresponding to the metabolism of either lipid or glucose represents the common mechanism underlying the pathogenesis of GLMD. The liver and adipose tissue are the major metabolic organs responsible for energy utilization and storage, respectively. This review article aims to summarize the current advances in the investigation of the functional roles and the underling mechanisms of the interplay between the liver and adipose tissue in the modulation of GLMD development. Fibroblast growth factor 21 (FGF21) and adiponectin represent the two major hormones secreted from the liver and adipose tissues, respectively. FGF21 exerts pleiotropic effects on regulating glucose and lipid homeostasis majorly through inducing the expression and secretion of adiponectin. Therefore, FGF21-adiponectin axis functions as the key mediator for the crosstalk between the liver and adipose tissue to exert the beneficial effects on the maintenance of the homeostasis of energy consumption. The liver- and adipose tissue-derived factors with pleiotropic effects on regulating of lipid and glucose metabolism function as the key mediator for the crosstalk between these two highly active metabolic organs, thereby coordinating the initiation and development of GLMD.  
      Keywords:obesity;type 2 diabetes mellitus;insulin resistance;glucolipid metabolic disease;Chinese Medicine   
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      Published:2021-08-27
    • Hao-ying Dou,Yuan-yuan Wang,Nan Yang,Ming-li Heng,Xuan Zhou,Huai-en Bu,Fang Xu,Tie-niu Zhao,He Huang,Hong-wu Wang
      2017, 23(6): 415-424. DOI: 10.1007/s11655-015-2290-3
      Abstract:To examine the association of genetic variants with characteristic symptoms of type 2 diabetes mellitus (T2DM). A matched case-control study was performed to investigate the association between common variants in four genes (CDKAL1, GLIS3, GRK5, and TCF7L2) and symptoms of T2DM. Symptoms were examined with questionnaire for 710 subjects. Genomic DNA was extracted from peripheral blood mononuclear cell by salting-out procedure. Genotyping was carried out by direct sequencing of the unpurified polymerase chain reaction products. Most of the T2DM patients pressented characteristic symptoms, such as feeling weak in limbs (P =0.0057), hand tremor (P =0.0208), bradymasesis (P =0.0234), and polyuria (P =0.0051). Some of the T2DM patients shared characteristic symptoms, such as desire for cold drinks (P =0.0304), polyphagia (P =0.0051), and furred tongue (P =0.028). The impaired glucose regulation (IGR) cases took only one characteristic symptom of frequent micturition (P =0.0422). GLIS3 rs7034200 and GRK5 rs10886471 were significantly associated with increased T2DM risk (GLIS3 rs7034200 under dominant model: P=0.0307; GRK5 rs10886471 under recessive model: P=0.0092). However, only the rs10886471 polymorphism in GRK5 showed a significant effect on both differentiated symptoms and T2DM risk. The C-allele was involved in both dampness-heat encumbering Pi (Spleen) syndrome (P =0.047) and qi-yin deficiency syndrome (P =0.002) via increased GRK5 expression. Both T2DM and IGR exhibited its corresponding characteristic symptoms. The variants of GRK5 were involved with both qi-yin deficiency syndrome and dampness-heat encumbering Pi syndrome.  
      Keywords:type 2 diabetes mellitus;impaired glucose regulation;Chinese Medicine;syndromes;genetic variants   
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      Published:2021-08-27
    • Lin Li,Yan-lin Li,Yun-feng Zhou,Zheng-yan Ge,Li-li Wang,Zhi-qiang Li,Yu-jie Guo,Long Jin,Ye Ren,Jian-xun Liu,Yang Xu
      2017, 23(6): 425-432. DOI: 10.1007/s11655-016-2595-x
      Abstract:To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe (降糖消脂方, JXR) in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were randomly divided into normal control group and diabetic group. Rats in the diabetic group were induced by intraperitoneal administration of STZ (50 mg/kg), and subdivided into 5 groups. Rats in the diabetic control group were given saline; four treatment groups were given metformin (300 mg/kg), JXR (2, 4 and 8 g/kg) respectively for 8 weeks, while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle. Body weight and food intake were measured every week. The hypoglycaemic effects were determined by testing fasting blood glucose (FBG) every other week, and hemoglobin A1c (HbA1c), insulin, and glucagon at the end of the treatment. The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining, and periodic acid-schiff staining. The effects were further evaluated by serum superoxide dismutase (SOD) activity and malondialdehyde (MDA). High-dose JXR significantly reduced FBG and HbA1c level at the 8th week of administration (P<0.01, P<0.05). JXR significantly increased insulin level (P<0.05), and decreased glucagon level (P<0.05). JXR showed the antioxidant defense with increased SOD activity and decreased MDA contents in diabetic rats. Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups. Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment. JXR have protective effect of diabetic retinopathy and its mechanism may be associated with the obvious hypoglycemic and antioxidant effect.  
      Keywords:Jiangtang Xiaozhi Recipe;Chinese Medicine;streptozotocin;diabetes mellitus;diabetic retinopathy   
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      Published:2021-08-27
    • Jinous Asgarpanah,Seyyed Jamal Hashemi,Elham Hashemi,Kiana Askari
      2017, 23(6): 433-437. DOI: 10.1007/s11655-015-2181-7
      Abstract:To investigate the antifungal activities of the extracts and sub-fractions of Phlomis olivieri, Verbascum speciosum, Sambucus ebulus and Erigeron hyrcanicus, four Persian medicinal plants used in Iranian folk medicine. Evaluation of the antifungal activity was performed on the clinical isolates of pathogenic fungi including Aspergillus fumigatus, A. flavus, Trichophyton mentagrophytes, T. rubrum, T. verrucosum, Microsporum canis, M. gypseum and Epidermophyton floccosum, and the yeast Candida albicans. The susceptibility tests were done by agar well diffusion method. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of active extracts and sub-fractions were measured using method of National Committee for Clinical Laboratory Standards (NCCLS). Only P. olivieri sub-fractions were found to have fungicidal activity among the other investigated plants. The MIC and MFC was found to be high in petroleum ether, chloroform and ethyl acetate fractions (100 and 200 mg/mL) against the studied pathogenic fungi and the yeast Candida albicans. P. olivieri sub-fractions significantly inhibited the growth of all pathogenic fungi and the yeast studied. If the antifungal activity of P. olivieri is confirmed by in vivo studies and if the responsible compound (s) is isolated and identified, it could be a good remedy for mycotic infections.  
      Keywords:antifungal activity;Phlomis olivieri;Verbascum speciosum;Sambucus ebulus;Erigeron hyrcanicus   
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      Published:2021-08-27
    • Chao-feng Hu,Li-ping Sun,Qin-he Yang,Da-xiang Lu,Sen Luo
      2017, 23(6): 438-444. DOI: 10.1007/s11655-016-2617-8
      Abstract:To investigate the effect of ginsenosides from stems and leaves of ginseng on ethanol-induced lipid deposition in human L02 hepatocytes. L02 cells were exposed to ethanol for 36 h and treated with or without ginsenosides. The viability of L02 cells was evaluated by methylthiazolyldiphenyl-tetrazolium bromide assay and the triglyceride (TG) content was detected. Lipid droplets were determined by oil red O staining. Intracellular reactive oxygen species (ROS) production and the mitochondrial membrane potential were tested by flow cytometry. The ATP level was measured by reverse phase high performance liquid chromatography. The expression of cytochrome p450 2E1 (CYP2E1) and peroxisome proliferator-activated receptor α (PPARα) was detected by reverse transcriptase-polymerase chain reaction and Western blotting, respectively. Ethanol exposure resulted in the increase of TG level, lipid accumulation and ROS generation, and the decrease of mitochondrial membrane potential and ATP production in the cells. However, ginsenosides significantly reduced TG content (9.69±0.22 μg/mg protein vs. 4.93±0.49 μg/mg protein, P<0.01), and ROS formation (7254.8±385.7 vs. 5825.2±375.9, P<0.01). Meanwhile, improvements in mitochondrial membrane potential (10655.33±331.34 vs. 11129.52±262.35, P<0.05) and ATP level (1.20±0.18 nmol/mg protein vs. 2.53±0.25 nmol/mg protein, P<0.01) were observed by treatment with ginsenosides. Furthermore, ginsenosides could down-regulate CYP2E1 expression (P<0.01) and upregulate PPARα expression (P<0.01) in ethanol-treated cells. Ginsenosides could prevent ethanol-induced hepatocyte steatosis in vitro related to the inhibition of oxidative stress and the improvement of mitochondrial function. In addition, the modulation of CYP2E1 and PPARα expression may also play an important role in the protective effect of ginsenosides against lipid accumulation.  
      Keywords:Ginsenosides;hepatocyte steatosis;reactive oxygen species;mitochondrial function;cytochrome P450 2E1;peroxisome proliferator-activated receptor α   
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      Published:2021-08-27
    • Xiao-ping Huang,Hua Tan,Bei-yang Chen,Chang-qing Deng
      2017, 23(6): 445-452. DOI: 10.1007/s11655-015-1965-0
      Abstract:To explore the effects and molecular mechanisms of the combination between total Astragalus extract (TAE) and total Panax notoginseng saponins (TPNS) against cerebral ischemia-reperfusion injury. C57BL/6 mice were randomly divided into sham-operated group, model group, TAE (110 mg/kg) group, TPNS (115 mg/kg) group, TAE-TPNS combination group and Edaravone (4 mg/kg) group, treated for 4 days, then, cerebral ischemia-reperfusion injury was established by bilateral common carotid artery (CCA) ligation for 20 min followed by reperfusion for 1 and 24 h. TPNS could increase adenosine triphosphate (ATP) level, TAE and TAE-TPNS combination increased ATP, adenosine diphosphate (ADP) contents and Na+-K+-ATPase activity, and the effects of TAE-TPNS combination were stronger than those of TAE or TPNS alone after reperfusion for 1 h. After reperfusion for 24 h, TAE, TPNS and TAE-TPNS combination significantly increased neurocyte survival rate and decreased the apoptosis rate as well as down-regulated the expression of phosphorylated c-June N-terminal kinase1/2 (p-JNK1/2), cytochrome C (Cyt C), cysteine aspartic acid-specific protease (Caspase)-9 and Caspase-3. Furthermore, the effects in TAE-TPNS combination were better than those in TAE or TPNS alone. The combination of TAE 110 mg/kg and TPNS 115 mg/kg could strengthen protective effects on cerebral ischemia injury, the mechanism underlying might be related to improving jointly the early energy metabolism, and relieving the delayed apoptosis via inhibiting the mitochondrial apoptosis pathway of JNK signal transduction.  
      Keywords:total Astragalus extract;total Panax notoginseng saponins;combination;cerebral ischemia-reperfusion;energy metabolism;C-Jun N-terminal kinase signal transduction;mitochondrial apoptosis pathway;Chinese Medicine   
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      Published:2021-08-27
    • Yu-tong Lu,Jie Li,Xin Qi,Ying-xia Pei,Wen-guang Shi,Hong-sheng Lin
      2017, 23(6): 453-460. DOI: 10.1007/s11655-016-2734-4
      Abstract:To observe the intervention effect of Shugan Jianpi Formula (疏肝健脾方, SGJPF) on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the development of breast cancer. The breast cancer model was induced by inoculation of breast cancer cells, the depression model was induced by chronic stress stimuli, and the depression cancer model was established by combining the two factors. The mice were divided into 7 groups: normal control, depression model, tumor model, depression tumor model, SGJPF, chemotherapy, and SGJPF+chemotherapy groups. The last 3 groups were depression breast cancer mice and treated respectively with SGJPF, chemotherapy drug gemcitabine (GEM), and SGJPF alongside GEM. The condition of the mice was evaluated by the expression of 5-hydroxytryptamine in hippocampus after the sucrose water test and open field test, weight change, and survival time. Tumor growth was monitored with in vivo imaging. Flow cytometry was used to analyze the level of myeloid-derived suppression cell (MDSC) in the mouse spleen, T cell subsets, and the early apoptosis of CD8+ T cells. The SGJPF+GEM group had the highest inhibition rate and the longest survival time (P<0.01). The MDSC level and the apoptosis rate of CD8+ T cells was the highest in the SGJPF+GEM group (P<0.05). Depressive disorders and tumor growth could suppress the immune function of mice to different degrees, and the microenvironment in late 4T1 inflammatory breast cancer may play an important role in the pathological process. SGJYF could regulate the immune microenvironment by reducing CD8+ T lymphocyte apoptosis and tumor cell activity, increasing immune surveillance capability, and inhibiting MDSC proliferation, thus prolonging the survival time of tumor-bearing mice.  
      Keywords:Breast Cancer;Shugan Jianpi Formula;Chinese Medicine;myeloid-derived suppression cell;depressive disorders;apoptosis   
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      Published:2021-08-27
    • Jie-wei Luo,Xiao-rong Meng,Xiao Yang,Ji-xing Liang,Fu-yuan Hong,Xing-yu Zheng,Wei-hua Li
      2017, 23(6): 461-468. DOI: 10.1007/s11655-016-2461-x
      Abstract:To determine the gene location of two Gitelman syndrome (GS) family SLC12A3 genes and explore treatments using Chinese medicine (CM) prescriptions. In order to locate the two GS mutations, samples were collected from 11 people from two different pedigrees for direct genetic sequencing and comparison of the 26 exons of SLC12A3. Furthermore, the change of serum potassium was monitored throughout the therapy and those two probands undertook a sequential superposition of Western medicine (including potassium, Panangin and potassium-sparing diuretics) with CM prescription based on Buyang Huanwu Decoction (补阳还五汤) and Sijunzi Decoction (四君子汤). The treatment included three stages, oral potassium chloride for the first 2 weeks (stage 1), potassium-sparing diuretic and Panangin with potassium chloride for the next 2 weeks (stage 2), CM along with the medicine in stage 2 for the final 2 weeks (stage 3). The three mutations occurring in proband 1 from pedigree I were Thr60Met, 965-1_976del13ins12 (small indels mutation) and Ala122Ala (homozygous silent mutation). Likewise, three mutations, Asn359Lys, Thr382Met and Arg913Gln, appeared in the proband 2 from pedigree II. The serum potassium levels increasing from baseline to sequential stages were 1.63 mmol/L (baseline), 2.5 mmol/L (stage 1), 3.1 mmol/L (stage 2) and 3.9 mmol/L (stage 3) in the proband 1, and 2.8 mmol/L (baseline), 3.1 mmol/L (stage 1), 3.5 mmol/L (stage 2) and 4.3 mmol/L (stage 3) in the proband 2, respectively. The symptoms (numbness of limbs, weakness, palpitations, etc.) of both probands were all alleviated. The mutations of both GS pedigrees can be defined as compound heterozygous mutations, most of which are known as missense mutations. Applying CM could be an appropriate choice for future intervention of GS.  
      Keywords:Gitelman syndrome;mutation;SLC12A3 gene;Chinese Medicine   
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      Published:2021-08-27
    • Yu Zhang,Li-li Qian,Jian-ping Shen,Jun-fa Chen,Yan-ting Gao,Jing-jing Xiang,Bao-dong Ye,Yu-hong Zhou
      2017, 23(6): 469-473. DOI: 10.1007/s11655-016-2276-9
      Abstract:To observe the influence of treatment based on Chinese medicine pattern identification on cellular immunophenotype of the myelodysplastic syndrome (MDS). Sixty patients with MDS were randomly and equally assigned to the treatment group and the control group using a randomized digital table. Thirty patients in each group included 3 risk levels (low, moderate and high risks) with each level 10 patients according to the international prognostic scoring system. The control group was given conventional therapy which was also used in the treatment group. While the treatment group was given Zuogui Pill (左归丸) and Yougui Pill (右归丸) for low risk patients; Qingwen Baidu Decoction (清瘟败毒饮) and Bazhen Decoction (八珍汤) for moderate risk patients; Gexia Zhuyu Decoction (膈下逐瘀汤) and Qinghao Biejia Decoction (青蒿鳖甲汤) combined with Shiquan Dabu Decoction (十全大补汤) for high risk patients. After the treatment, the differences of overall response rate and immunophenotype (CD13, CD14, CD15, CD33 and CD34) of each group were analyzed. The overall response rate of the treatment group was significantly higher than the control group in low risk and moderate risk patients (P=0.029), there was no statistical differences of overall response rate between the treatment group and the control group in high risk patients (P=0.089). The expressions of CD13, CD14, CD33 and CD34 in all three risk levels of the treatment group were obviously decreased after the treatment, while CD15 in all three risk levels of the treatment group was obviously increased after the treatment (P<0.05 or P<0.01). Meanwhile, the difference values of CD13 and CD33 in low risk level of the treatment group, CD33 and CD34 in moderate risk level of the treatment group as well as CD34 and CD15 in high risk level of the treatment group, were all greater than the control groups and they were statistically significant (P<0.05 or P<0.01). It shows a better therapeutic effect if the MDS patients treated with Chinese medicine pattern identification in addition to conventional therapy. Since the treatment may inhibit the malignant clones and improve the dysmaturity of granulocyte differentiation, it is a feasible option in clinical practice.  
      Keywords:myelodysplastic syndrome;Chinese Medicine;pattern identification;immunophenotype   
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      Published:2021-08-27
    • Jing-xian Li,Zhi-cheng Qiao,Hong-xia Ma,Yi-ting Li,En-chang Li,Peng-cheng Ji,Gang Huang
      2017, 23(6): 474-480. DOI: 10.1007/s11655-016-2628-5
      Abstract:To construct a quantitative ethical evaluation index system for the clinical approval of medical technology in China. Exploratory factor analysis (EFA) and first-order confirmatory factor analysis (CFA) based on a structure equation model (SEM), higher-order CFA and normalisation were used to establish an ethical evaluation index system for the clinical approval of medical technology. Data were processed in SPSS 13.0 and Lisre l5.3. There were 52 third class indices, 15 second class indices, and 3 first class indices in this ethical evaluation index system. The weight of each index was calculated by normalisation. This study developed a three-level ethical evaluation index system, comprising 70 indices, for the clinical approval of medical technology.  
      Keywords:medical technology;ethical review;factor analysis;structural equation model   
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