Traditional Chinese medicine Lingguizhugan decoction treating non-alcoholic fatty liver disease with spleen-yang deficiency pattern: Study protocol for a multicenter randomized controlled trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease characterized by excessive fat accumulation in the liver. One of the underlying pathophysiological mechanisms is insulin resistance (IR). Traditional Chinese medicine (TCM) has showed potential benefits in the management of NAFLD. Lingguizhugan decoction (LGZG) is a representative Chinese herbal formula; however, there is still no rigorous clinical trial supporting its application. METHODS/DESIGN: This study will be a three-arm, dose-optimization, randomized, double-blinded, placebo-controlled clinical trial. A total of 243 patients with NAFLD will be recruited and randomly assigned to the standard dose LGZG (SLGD) group, low dose LGZG (LLGD) group, or the placebo group based on a ratio of 1:1:1. The treatment period will be 12 weeks and the follow-up period will last 4 weeks. The primary outcome will be the proportions of participants with at least a 1-unit decrease of HOMA-IR from baseline to 12 weeks. Secondary outcomes will include the changes of body weight, body mass index, liver function, blood lipid metabolism, blood glucose metabolism, inflammatory responses, liver-kidney echo ratio by ultrasound, and various scales. Biological samples will also be collected for future researches on mechanism exploration. DISCUSSION: This study will provide initial evidence regarding the efficacy and safety of LGZG in the treatment of NAFLD with spleen-yang deficiency pattern and promote its application in community healthcare centers. In addition, potential mechanisms will be explored based on studies of oral and gut microbiota. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800014364. Registered on 1 January 2018. The final protocol version was V3.0.

Traditional Chinese Medicine syndrome elements of male infertility revealed by latent tree model analysis.

OBJECTIVE: To explore the features of Traditional Chinese Medicine (TCM) syndromes in male infertility using computer-based analyses. METHODS: Latent class analysis was used to analyze the TCM syndrome data from 813 patients with male infertility and establish a latent tree model. RESULTS: A latent tree model with a Bayesian information criterion score of -11 263 was created. This model revealed that the characteristics of basic TCM syndromes in patients with male infertility were kidney Yang deficiency, kidney Qi deficiency, spleen Yang deficiency, liver Qi stagnation, Qi stagnation and blood stasis, and dump-heat; moreover, most patients with male infertility had complex syndromes (spleen-kidney Yang deficiency and liver Qi stagnation) rather than simple single syndromes. CONCLUSION: The hidden tree model analysis revealed the objective and quantitative complex relationships between the TCM symptoms of male infertility, and obtained the quantification and objective evidence of TCM syndromes in male infertility.

Novel chinmedomics strategy for discovering effective constituents from ShenQiWan acting on ShenYangXu syndrome.

Elucidation of the efficacy of traditional Chinese medicine (TCM) is of importance for scientists of modern medicine to understand the value of TCM clinical experience, and it is necessary to have a biological language to scientifically describe the efficacy of TCM. With this background?Chinmedomics has been proposed by our team, which includes integrating serum pharmacochemistry and metabolomics technology, defining theory and research methods for expressing the efficacy of TCMs based on the biomarkers discovery of TCM syndrome and elucidating the efficacy of TCM formulae, discovering effective constituents, and finally elucidating the scientific value of TCM. In the present study, the innovative chinmedomics strategy was conducted to evaluate the therapeutic effects of ShenQiWan (SQW) acting on ShenYangXu (kidney-yang deficiency syndrome, KYDS). We analyzed the urine metabolic trajectory between the model and control groups, and identified the biomarkers by the multivariate analysis. We found that SQW caused significant restoration of abnormal metabolism of KYDs. Using the method of metabolomics, 17 potential urine biomarkers were analyzed through 4 repeated tests in our serial studies on SQW and KYDS. Under the premise of therapeutic efficacy, a total of 56 peaks were tentatively characterized in vivo by the use of serum pharmacochemistry. Correlation analysis between marker metabolites and in vivo constituents of SQW showed that 28 compositions had a close relationship with urine biomarkers of therapeutic effects, whichmight play a key role in the therapeutic effect of SQW. These compounds were imported into an online database to predict their targets. Twenty-three important potential targets were identified, which were related to the metabolism of steroid hormone, tryptophan utilization, and thyroid hormone. In conclusion, chinmedomics is a useful strategy for discovery of potentially effective constituents from complex TCM formulae.

[Effect of electroacupuncture at Zhongwan(CV 12) on skin microcirculatory blood perfusion units along the conception vessel in yang-deficiency volunteers].

OBJECTIVE: To observe the effect of electroacupuncture(EA) at Zhongwan(CV 12) on the energy metabolism along the conception vessel(CV) in volunteers with yang-deficiency constitution,and to explore the relationship of electroacupuncture regulation and body constitution. METHODS: Eighteen volunteers with mild constitution and 18 volunteers with yang-deficiency constitution were collected out of 200 students of Fujian University of TCM by body constitution questionnaire. Skin microcirculatory blood perfusion units (MBPU) at Danzhong (CV 17), Xiawan(CV 10) and Qihai(CV 6) of CV were measured by a laser Doppler flowmetry in the normal condition and after EA stimulation at Zhongwan(CV 12) for 20 min. RESULTS: (1)Before treatment, (1)MBPU values at Danzhong(CV 17), Xiawan(CV 10) and Qihai(CV 6) in the yang-deficiency constitution group were lower than those in the mild constitution group,but there was no statistical significance (both P>0. 05) except Danzhong(CV 17) (P<0. 01). (Z)As for the three acupoints in the mild constitution group, MBPU level of Danzhong(CV 17) was higher than that of Xiawan(CV 10) without statistical significance(P->0. 05),and MBPU values of Danzhong(CV 17) and Xiawan(CV 10) were higher than that of Qihai(CV 6) (both P<0. 01). (3About the three acupoints in the yang-deficiency constitution group, MBPU result of Danzhong(CV 17) was lower than the value of Xiawan(CV 10), but higher compared with Qihai(CV 6)(P<0. 05, P<0. 01). MBPU of Xiawan(CV 10) was higher than Qihai (CV 6) as well(P<0. 01). (2) MBPU values of Danzhong(CV 17), Xiawan(CV 10) and Qihai(CV 6) were increased apparently compared with those before treatment after EA stimulation at Zhongwan(CV 12) for 20 min in the two groups(all P<0. 01). (3) The rise rates of MBPU level about Danzhong(CV 17) and Qihai(CV 6) in the yang-deficiency constitution group were higher than those in the mild constitution group without statistical significance after EA at Zhongwan(CV 12) for 20 min(both P>0. 05). CONCLUSION: The energy metabolism in CV of volunteers with yang-deficiency constitution is declined, especially Danzhong(CV 17). EA can rise energy metabolism in CV of mild or yang-deficiency constitution volunteers through regulating MBPU along meridian.

[Correlation of propagated sensation along meridian and TCM constitution].

OBJECTIVE: To explore the correlation between propagated sensation along meridian (PSM) and TCM constitution at different age stages. METHODS: According to age, 840 participants were divided into a youth group (326 cases), a middle aged group (243 cases) and an elderly group (271 cases). The TCM constitution of all the participants was evaluated, and the PSM test was performed. The distribution of TCM constitution, the occurring rate and transmission of PSM in each group were observed and compared; the correlation between PSM and the TCM constitution was preliminary investigated by Logistic regression analysis. RESULTS: The distribution of nine types of TCM constitution in three groups:the proportion of normal constitution and partial constitution were significantly different (all P<0.05); the occurring rate and transmission of PSM in three groups were not significantly different (all P>0.05); the proportion of occurring rate for nine types of TCM constitutions in the whole population, from high to low, presented special intrinsic quality, neutral quality, yin-deficiency quality, qi-deficiency quality, yang-deficiency quality, damp-heat quality, phlegm-dampness quality, qi-stagnation quality and blood-stasis quality; besides, the proportion of occurring rate for different TCM constitutions in the youth group, middle aged group and elderly group was similar to that of whole population. The Logistic regression analysis results indicated the neutral quality (P=0.025) and special intrinsic quality (P=0.018) were positively while blood-stasis quality (P=0.043) was negatively related with PSM in all subjects; the qi-deficiency quality (P=0.025), phlegm-dampness quality (P=0.019), blood-stasis quality (P=0.012) and qi-stagnation quality (P=0.035) were negatively related with PSM in youth group; the neutral quality (P=0.001) was positively related with PSM inthe middle aged group; the neutral quality (P=0.006) and yin deficiency quality (P=0.004) were positively related with PSM in the elderly group. CONCLUSIONS: The occurrence of PSM in different age stages is related with TCM constitution, which could be increased in clinical treatment to improve acupuncture efficacy.

[Characteristics of Deqi Induced by Needling Zusanli (ST 36) in 527 Healthy Volunteers with Different Constitutions].

OBJECTIVE: To explore the relationship between the theory of constitution in terms of Chinese medicine and clinical efficacy of acupuncture treatment via analyzling the characteristics of Deqi during acupuncture stimulation of Zusanli (ST 36) in healthy volunteers with different constitutions. METHODS: In the present study, a total of 527 healthy undergraduate student volunteers (267 girls and 260 boys) were recruited. They received questionnaire first about their constitutions in accordance with Professor WANG Qi's Classification and Determination of Constitution in terms of Chinese medicine. Then, the subjects were asked to take a supine position on a check-bed, a qualified acupuncturist held a sterilized fifiform needle to rapidly insert it into ST 36 and manipulated the acupuncture needle with uniform reinforcing-reducing technique at a frequency of about 60-90 times/min and an amplitude of 0.3-0.5 cm. The status of Deqi was assessed by using visual analogue scale (VAS). RESULTS: Needling sensations mainly involve soreness, numbness, heaviness, distension, dull pain and propagated sensations along meridian (PSC). During acupuncture stimulation, most subjects experienced distension sensation, accounting for 90.3%, followed by soreness, accounting for 45.9%. Except for PSC reaction, the rest 5 needling sensations had no statistical difference in their occurrence rates in those subjects with different constitutions (P>0.05). The PSC appeared a higher incidence in yin-yang harmony(balanced) constitution subjects than in qi- deficiency, yang-deficiency, blood-stagnation and qi-stagnation constitution subjects (P<0.05). The intensity of soreness was obviously stronger in the balanced constitution subjects than in qi-deficiency, yang-deficiency, yin-deficiency, phlegm-damp, damp-heat and qi-stagnation constitution subjects (P<0.05), while the intensity of distension sensation was apparently stronger in the balanced constitution subjects than in simpleyang-deficiency subjects (P<0.05). CONCLUSIONS: Except for PSC, the Deqi sensations of soreness, numbness, heaviness, distension and dull pain induced by acupuncture stimulation of ST 36 are comparable in the occurrence rates in healthy volunteer subjectswith different (9 types of) constitutions in terms of Chinese medicine, whereas the intensity of soreness may be the important factor for acupuncture induced pain relief. A certain correlation between the constitution and acupuncture effectiveness exists, suggesting that acupuncture treatment should vary from patient to patientin clinical practice.

[Clinical observation on obesity and hyperlipidemia of yang deficiency of spleen and kidney syn- drome in female patients treated with warm acupuncture combined with auricular acupuncture].

OBJECTIVE: To compare the differences of clinical effects in female patients with obesity and hyperlipidemia of yang deficiency of spleen and kidney syndrome between warm acupuncture combined with auricular acupuncture and simple warm acupuncture. METHODS: One hundred and thirty patients were randomly divided into an observation group and a control group, 65 cases in each one. In the control group, acupuncture was used at Pishu (BL 20), Zhongwan(CV 12), Shenshu(BL 23), Zhongji(CV 3), Guanyuan(CV 4), Mingmen(GV 4), Taibai(SP 3), Fenglong(ST 40), etc.; warm acupuncture was applied at Pishu(BL 20), Zhongwan(CV 12), Shenshu(BL 23) and Zhongji(CV 3); the treatment was required once every two days and for 3 months continuously. In the observation group, based on the treatment in the control group, thumbtack intradermal needles were embedded at auricular points, including pi(CO13), shen(CO10), pangguang(CO9), sanjiao(CO17), neifenmi(CO18), neishengzhiqi(TF2), etc. Obesity indices [body mass(W), obesity degree(A), body mass index(BMI), body fat percentage(F%)] blood lipid indices [serum total cholesterol(TC), triglyceride(TG), low density lipoprotein(LDL-C), high density lipoprotein(HDL-C)] and clinical efficacy were observed before and after treatment in the two groups. Results After treatment in the two groups, the obesity indices of W, A, BMI, F% and the blood lipid levels of TC, TG, LDL-C were obviously decreased compared with those before treatment (all P<0. 01) and the HDL-C levels were apparently increased than those before treatment (both P<0. 01). After treatment, the improvement of TC and HDL-C in the observation group was superior to that in the control group (both P<0. 01). The difference was not statistically significant in the aspect of improving every obesity index between two groups (all P>. 05). The comprehensive total effective rate of the observation group was 95.4% (62/65), which was better than 84. 6% (55/65) of the control group (P<0. 001). CONCLUSION: Warm acupuncture combined with auricular acupuncture and simple warm acupuncture can both benignly adjust abnormal lipid metabolism of obesity patients with hyperlipidemia, and warm acupuncture combined with auricular acupuncture are superior to simple warm acupuncture treatment on antiobesity action and improving the TC and HDL-C levels.

[Acupuncture Stimulation of Acupoints of Multiple Meridians for Patients with Diminished Ovarian Reserve of Both Yin and Yang Deficiency].

OBJECTIVE: To observe the effect of acupuncture stimulation of acupoints of the Conception Vessel, Kidney Meridian, Spleen Meridian, and Bladder Meridian on menstrual cycles and duration, and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estrogen 2 (E(2)) levels in patients with diminished ovarian reserve (DOR). METHODS: A total of 96 patients with DOR of both yin and yang deficiency were randomly divided into medication group and acupuncture group (n = 48 cases in each group). Patients of the medication group were treated by Estradiol Valerate tablets, 2 mg/d on the first 10 days, and Estradiol Cyproterone, 3 mg/d from day 11 to 21, followed by 5 -7 days' rest, and the next therapeutic course, continuously for 6 months. For patients of the acupuncture group, filiform acupuncture needles were separately inserted into every 5 points of the Conceptional Vessel, Kidney, Spleen and Bladder Meridians, manipulated with uniform reinforcing and reducing methods till Deqi, and retained for 40 min. The treatment was conducted once daily for consecutive 10 days in one menstrual cycle, beginning from the 10(th) day on after menstruation, which was repeated for 6 months. The integrative scores (normal = 0, mild=2, moderate=4 and severe=6 points) of menstrual cycle, menstrual duration, amount, color, quality [blood blot or ame- nia, symptoms of traditional Chinese medicine (TCM)] were assessed according to "Guiding Principles for Clinical Trials of New Drugs of Chinese Materia Medica". Serum FSH, LH and E(2) contents were detected by Roche's electrochemical luminescence method. RESULTS: After the treatment, of the two 48 cases in the medication and acupuncture groups, 12 (25.0%) and 20 (4.7) were cured, 11 (22.9 %) and 12 (25.0 %) experienced marked improvement in their symptoms, 20 (41.7%) and 10 (20.8%) were effective, and 5 (10.4%) and 6 (12.5%) failed, with the effective rate being 89.6% and 87.5%, respectively. The integral score of TOM symptoms, menstrual cycle, serum FSH, LH and E2 contents were considerably diminished in both groups after 6 months of treatment (P<0.05), and the TOM symptom score, menstrual cycle, and serum FSH, LH and E2 levels were significantly lower in the acupuncture group than in the medication group 6 months after cease of the treatment (P<0.05), while the menstrual duration in each cycle was notably longer in both groups after the treatment, and evidently longer in the acupuncture group than in the medication group 6 months after cease of the treatment (P<0.05). No significant differences were found between the two groups in the effective rate, score of TOM symptoms, menstrual cycle and duration, and serum FSH, LH and E(2) contents following the treatment (P>0.05). CONCLUSION: Acupuncture stimulation of acupoints of the Conception Vessel, Kidney, Spleen, and Bladder Meridians is effective in improving clinical symptoms of DOR patients with deficiency of both yin and yang, and has a longer effect, which may be closely associated with its functions in lowering serum FSH, LH and E(2) levels through regulating the hypothalamic-pituitary-ovarian axis.

Spleen-yang-deficiency patients with polycystic ovary syndrome have higher levels of visfatin.

OBJECTIVE: To study serum visfatin levels in women with polycystic ovary syndrome (PCOS) grouped by Traditional Chinese Medicine (TCM) patterns. To study the correlations of serum visfatin levels with homeostatic model assessment insulin resistance (HOMA-IR), fasting plasma glucose (FPG), fasting insulin (FINS), body mass index (BMI), testosterone (T), total cholesterol (TC), and triglycerides (TG). METHODS: Two hundred and twelve PCOS patients were placed into the following TCM pattern subgroups: Kidney-Yang deficiency (KYD) group, Spleen-Yang deficiency (SYD) group, stagnant Liver-Qi transforming into heat (SLQTH) group, and Kidney-Yin deficiency (KYIND) group. The correlations between serum visfatin levels and HOMA-IR, FPG, FINS, BMI, T, TC, and TG were analyzed. RESULTS: Of all patients with PCOS, there were 82 in the KYD group (38.6%), 67 in the SYD group (31.6%), 37 in the SLQTH group (17.5%), and 26 in the KYIND group (12.3%). Visfatin levels in all PCOS subgroups were higher than those in the control group (P < 0.01 or P < 0.05). Among these subgroups, the visfatin levels in the SYD group were significantly higher than those in the other three TCM pattern groups (P < 0.05). There were no statistical differences among the remaining three pattern groups. The levels of BMI, FINS, HOMA-IR, T, and TG were significantly higher in all subgroups than those in the control group (P < 0.05). There were no significant differences in FPG and TC between all PCOS subgroups and the control group (P > 0.05). The SYD group had higher levels of FINS and HOMA-IR compared with the KYD, SLQTH, and KYIND groups (P < 0.05). In all subgroups, after controlling for BMI, TG, TC, and age, visfatin was positively correlated with FINS (r = 0.197, P = 0.015) and HOMA-IR (r = 0.173, P = 0.033), and was not correlated with T. CONCLUSION: KYD and SYD patterns are most common in PCOS patients. Increased visfatin is a common pathophysiologic manifestation in PCOS patients. The SYD group had the highest levels of visfatin, and visfatin was positively correlated with FINS and HOMA-IR.

[Clinical study on primary osteoporosis treated with spreading moxibustion for warming yang and activating blood circulation].

OBJECTIVE: To observe the efficacy on primary osteoporosis treated with spreading moxibustion for warming yang and activating blood circulation so as to provide the effective clinical therapeutic methods for osteoporosis. METHODS: Sixty cases of primary osteoporosis were randomized into a spreading moxibustion group (30 cases) and a calcium tablet group (30 cases). In the calcium tablet group, caltrate was prescribed for oral administration, 600 mg per day. In the spreading moxibustion group, on the basis of the treatment as the calcium tablet group, the spreading moxibustion was applied at Dazhui (GV 14) to Yaoshu (GV 2) for warming yang and activating blood circulation. The duration of treatment was 12 weeks. Visual analogue scale (VAS) score, TCM clinical symptom score and bone mineral density (BMD) were observed and compared before and after treatment in the patients between the two groups. RESULTS: VAS scores were reduced apparently after treatment in the two groups (both P < 0.01) and the results in the spreading moxibustion group were obviously superior to that in the calcium tablet group (2.36 +/- 0.43 vs 4.52 +/- 0.35, P < 0.01). BMD were all increased in the two groups (P < 0.05, P < 0.01) and the results in the spreading moxibustion group were superior to those in the calcium tablet group (both P < 0.05). The total clinical effective rate was 86.67% (26/30) in the spreading moxibustion group, apparently better than 63.33% (19/30) in the calcium tablet group (P < 0.05). TCM clinical symptom scores after treatment were all reduced apparently in the two groups (both P < 0.01), and the result in the spreading moxibustion group was obviously superior to that in the calcium tablet group (4.72 +/- 1.90 vs 6.82 +/- 2.30, P < 0.01). The total effective rate of TCM symptoms was 93.33% (28/30) in the spreading moxibustion group, apparently better than 70.00% (21/30) in the calcium tablet group (P < 0.05). CONCLUSION: The combined therapy of spreading moxibustion for warming yang and activating blood circulation and the oral administration of caltrate apparently relieves pain and TCM clinical symptoms, improves BMD in the patients of osteoporosis and achieves definite clinical efficacy in the patients of osteoporosis.

Metabolic profiling reveals therapeutic biomarkers of processed Aconitum carmichaeli Debx in treating hydrocortisone induced kidney-yang deficiency syndrome rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Kidney-yang deficiency syndrome (KYDS) is a diagnostic pattern in traditional Chinese medicine (TCM) and clinical data showed that the unbalance in adrenal cortical hormone is the key issue in KYDS patients. The processed Ranunculaceae aconitum carmichaeli debx (bai-fu-pian in Chinese, BFP) is one of the most commonly used Chinese herbs for treating KYDS. The present study was conducted to explore the therapeutic biomarkers of the BFP in treating hydrocortisone administration induced KYDS rats. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomly divided into five groups with six in each group. KYDS in rats was induced by i.p. injection of hydrocortisone at the dose of 10mg/kg per day for 15 days as described previously. The rats with KYDS were administered orally, starting from the day of hydrocortisone administration stopped, with BFP extract at the dose of 0.32g/kg, 0.64g/kg and 1.28g/kg per day respectively for 15 days. The blood samples were collected for the liquid chromatography quadruple time-of-flight mass spectrometry (LC-Q-TOF-MS) test, as well as radioimmunoassay to determine the concentrations of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and adrenocorticotrophic hormone (ACTH). The metabolic responses to BFP administration were investigated by using the principal components analysis (PCA) and orthogonal partial least squares analysis (OPLS). Bioinformatics analyses were performed by using the Ingenuity Pathway Analysis (IPA). Variance analysis and linear regression analysis were used in this study. RESULTS: The signs and concentrations of cAMP, cGMP and ACTH in the model rats were similar to those previously described about KYDS rats and BFP treatment can reverse the changes. Seventeen significantly changed metabolites among different groups were identified. Thirteen metabolites were identified in the KYDS rats comparing to healthy rats with nine up-regulated and four down-regulated. After BFP treatment at three dosages, five up-regulated metabolites including phosphate, betaine, (4-hydroxyphenyl) acetaldehyde, 5-hydroxyindol-3-acetic acid and 5'-phosphoribosyl-N-formylglycinamide were dose-dependently reversed. The network analysis with IPA showed that four canonical pathways including superpathway of methionine degradation, purine nucleotides de novo biosynthesis II, tyrosine synthesis and serotonin receptor signaling involved the therapeutic mechanism of BFP in treating the KYDS rats. CONCLUSIONS: Five therapeutic biomarkers (phosphate, betaine, (4-hydroxyphenyl) acetaldehyde, 5-hydroxyindol-3-acetic acid and 5'-phosphoribosyl-N-formylglycinamide) and two corresponding canonical pathways (amino acid metabolism and purine nucleotide metabolism) were identified to be involved in the therapeutic mechanism of BFP treating the KYDS.

[Research on building method of spleen kidney Yang deficiency diarrhea rats model].

Spleen kidney Yang deficiency (SKYD) diarrhea is a common syndrome in tranditional Chinese medicine (TCM). Until now, there is not an ideal SKYD diarrhea rat model for the research. In this study, we compared single factor way (method I, injecting hydrocortisone and gavaging Sennae Folium) with compound factors way(method II, gavaging adenine, improper diet, exhaustion, and gavaging Sennae Folium) on establishing SKYD diarrhea rat model. After modelling, diarrhea index, D-xylose excretory rate, NOS/cGMP signal transduction system, organ index and histopathology examination were used to evaluate the two ways. The results showed that, compared with health group, all the assessment criterias of method I and method II had significant differences (P < 0.01, 0.05). In addition, the index such as diarrhea index, NOS/cGMP signal transduction system, organ index (kidney, testis and thymus) and histopathology examination had significant differences (P < 0.01, 0.05) between method I and method II. In conclusion, the compound factors modelling method better conforms to the symptom of diarrhoea model caused by SKYD. This new modelling method provides a basis for studying on TCM astringents warming and tonifying the spleen and kidney, relieving diarrhea.

Bone marrow angiogenesis in patients presenting with differential Chinese medicine syndrome: correlation with the clinico-pathological features of aplastic anemia.

OBJECTIVE: To explore differences in bone marrow angiogenesis seen in aplastic anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome, and to correlate these differences with clinical pathology. METHODS: Thirty-five patients were enrolled, including 18 with "yang deficiency syndrome" and 17 with "yin deficiency syndrome." Bone marrow biopsies and serum were collected. Microvessel density (MVD) and positive expression of vascular endothelial-derived growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible factor -1α (HIF-1α), and VEGF expression were assayed by enzyme-linked immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. RESULTS: Counts for leukocytes, absolute neutrophils and platelets in "yin deficiency syndrome" were lower than those found in "yang deficiency syndrome" (P<0.05). MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in AA, especially in "yin deficiency syndrome" (P<0.01 or P<0.05). "Yin deficiency syndrome" displayed decreased VEGF and LDH expression, and enhanced expression of HIF-1α as compared to "yang deficiency syndrome" (P<0.05). Levels of IL-4 and IL-6 were higher in AA (P<0.01), but IL-10 was decreased (P<0.05). High TNF-α expression was seen in "yang deficiency syndrome" and IFN-γ expression was decreased in "yin deficiency syndrome" as compared with normals (P <0.01 and P<0.05, respectively). CONCLUSION: AA patients have lower MVD than normals, especially in "yin deficiency syndrome." MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN-γ were negatively associated while IL-6 and TNF-α were positively associated with MVD.

[Determination pharmacokinetics parameters of raw and different processed epimediums by pharmacology effect method].

OBJECTIVE: To determine the pharmacokinetics parameters of raw and different processed epimediums with pharmacology effect method. METHODS: The kidney-yang deficiency model mice induced with hydrocortisone was used and oxidative stress level was taken as index to estimate main pharmacokinetics parameters of raw and different processed epimediums. RESULTS: After raw and different processed epimediums po. in mice, the main pharmacokinetics parameters were: raw epimedium AUC(0-t) = 184.77 (g/kg) x h, AUC(0-infinity) = 342.30 (g/kg) x h, MRT(0-t) = 5.95 h, MRT (0-infinity) = 28.58 h,Tmax, = 0.75 h, Cmax = 57.67 g/kg; Fried epimedium AUC(0-t) = 208.08 (g/kg) x h, AUC(0-infinity) = 523.95 (g/kg) x h, MRT(0-t) = 5.86 h, MRT(0-infinity) = 22.55h, Tmax = 1 h, Cmax = 62.53 g/kg; Fat-fried epimedium AUC (0-t) = 232.17 (g/kg) x h, AUC(0-infinity) = 629.96 (g/kg) x h, MRT(0-t) = 5.28 h, MRT(0-infinity) = 19.62 h, Tmax = 1.5 h, Cmax = 81.84 g/kg. CONCLUSION: The differences of Cmax and AUC between processed products and raw products are significant, and the sequence is as follows: fat-fried products > fried products > raw products.

[Treatment of ulcerative colitis with spleen and kidney yang deficiency by kuijiening plaster: a randomized controlled study].

OBJECTIVE: To explore the clinical efficacy of ulcerative colitis with spleen and kidney yang deficiency by kuijiening plaster and the impacts on IFN-gamma and IL-4 contents, as well as make the comparison with oral medication of sulfasalzine (SASP). METHODS: Sixty patients of ulcerative colitis with spleen and kidney yang deficiency were randomized into a Kuijiening plaster group, a SASP group and a combined therapy group, 20 cases in each one. In the Kuijiening plaster group, Kuijiening plaster and oral administration of placebo SASP were applied. The plaster was used at Shangjuxu (ST 37), Tianshu (ST 25), Zusanli (ST 36), Mingmen (GV 4) and Guanyuan (CV 4). In the SASP group, was applied Kuijiening plaster placebo at the points and SASP oral administration was adopted. In the combined therapy group, Kuijiening plaster and SASP oral administration were given. The duration of treatment was 60 days. The follow-up visit was 2 months after treatment. The comprehensive efficacy, the efficacy on TCM syndrome and the changes in serum IFN-gamma and IL-4 before and after treatment were compared among the three groups. RESULTS: The efficacy on TCM syndrome in the Kuijiening plaster was similar to the SASP group [85.0% (17/20) vs 75.0% (15/20), P > 0.05]. The efficacy on TCM syndrome in the Kuijiening plaster group was superior to the western medicine group [80.0% (16/20) vs 60.0% (12/20), P < 0.05]. The total effective rate of the comprehensive efficacy in the combined therapy group was 95.0% (19/20) and that of TCM syndrome efficacy was 90.0% (18/20), which were all superior to the other two groups (all P < 0.05). The differences in serum IFN-gamma and IL-4 were statistically significant before and after treatment in all of the three groups (all P < 0.05). The treatments in the three groups reduced serum IFN-gamma content and increased serum IL-4 content. The results in the Kuijiening plaster group were superior to the SASP group (P < 0.05) and the results in the combined therapy group were superior to the other two groups (all P < 0.05). CONCLUSION: Kuijiening plaster is effective in the treatment of ulcerative colitis of spleen and kidney yang deficiency, which is not inferior to that of SASP. The efficacy of kuijiening plaster on relieving TCM syndrome and improving body immunity is much superior to SASP. The effect is much better with SASP combined in the treatment.

[Evaluation of the key indicators in the pituitary-target gland axes in the animal model with shenyang deficiency syndrome using factor analysis].

OBJECTIVE: To evaluate the key indicators in the pituitary-target gland axes in the animal model of Shen-yang deficiency syndrome (SYDS). METHODS: The 8 biological indicators [thyroid stimulating hormone (TSH), 3, 3', 5-triiodothyronine (T3), thyroxine (T4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), adrenocorticotropic hormone (ACTH), and cortisol (CORT)] in the pituitary-target gland axes were grouped using factor analysis. Then the sensitivity of every indicator was calculated according to the sensitivity function defined in this paper, so as to find all the most sensitive indicators in every group as key indicators of SYDS. RESULTS: The key indicators in the early period of SYDS were T, LH, T4, and CORT. The key indicators in the middle period were LH,T, CORT, and ACTH. The key indicators in the late period were LH, T, CORT, and FSH. CONCLUSIONS: T, LH, and CORT were the common key indicators of the three periods, and other different key indicator of SYDS in the early, middle and late period were T4, ACTH, and FSH respectively, which changed from the thyroid axis to the adrenal axis and then to the gonadal axis as the period changed. The key indicators in the late period were mainly in the gonadal axis, showing gonadal dysfunction in the late period.

Traditional Chinese medicine diagnoses in persons with ketamine abuse.

OBJECTIVES: To explore the distribution of TCM patterns in ketamine users and the inter-rater reliability of TCM diagnosis among TCM practitioners. METHODS: Eighty-four subjects recruited from substance abuse clinics and non-governmental counseling services catering for ketamine abusers were examined by one or two TCM practitioners. The distribution and inter-rater reliability of the TCM diagnoses between the two TCM practitioners were described and measured. RESULTS: Seven TCM patterns were differentiated. The four most common patterns were the Heart Yin deficiency (29.8%), Kidney Yang deficiency (26.2% Kidney Yin deficiency (19.0%), and Spleen Yang deficiency (14.3%). The agreement between the two TCM practitioners was 59%; the kappa for the three most common patterns was 0.472 (P = 0.003). The proportion of men was lower in the Kidney Yin deficiency group (18.8%), in comparison to the Heart Yin deficiency (60.0%, P = 0.009) and Kidney Yang deficiency group (59.1%, P = 0.013). CONCLUSION: The differences between the TCM groups in terms of the source of referral and number of drug uses other than ketamine were of borderline significance. Further research should focus on validating diagnostic tools and improving inter-rater reliability in TCM to enhance the quality of clinical trials of TCM treatments for ketamine abuse.

An integrated plasma and urinary metabonomic study using UHPLC-MS: intervention effects of Epimedium koreanum on 'Kidney-Yang Deficiency syndrome' rats.

A metabonomic strategy based on UHPLC-MS with principal component analysis was developed to investigate the intervention effects of Epimedium koreanum on metabolism characters of 'Kidney-Yang Deficiency syndrome' rats. The rats were injected intraperitoneally hydrocortisone once daily for 15 days to simulate 'Kidney-Yang Deficiency syndrome' and then administered orally E. koreanum extract once daily for the following 15 days. Plasma and urine samples before hydrocortisone injection, on day 15 of hydrocortisone injection and on days 3, 6, 9, 12, 15 exposed to E. koreanum extract were collected. Significant metabolic disorders were observed in 'Kidney-Yang Deficiency syndrome' rats and sixteen potential biomarkers were identified. The disturbed plasma levels of phenylalanine, tryptophan, cholic acid, lysophosphatidylcholines and urinary levels of phenylalanine, hippurate, phenylacetylglycine, N(2)-succinyl-l-ornithine, creatinine, α-ketoglutarate, citrate, phenol sulfate, indoxyl sulfate, cresol sulfate in model rats were gradually restored to normal after administration of E. koreanum extract, which indicated that E. koreanum had time-dependent recovering effects via regulating oxidant-antioxidant balance, amino acid metabolism, lipid metabolism, energy metabolism, and gut microflora. This work highlights that metabonomics is a promising tool for studying the essence of Chinese medicine's syndrome theory and the action mechanism of traditional Chinese medicine, and provides scientific and reasonable information on safety and efficacy of traditional Chinese medicine.

[Comparative study on kidney tonifying and yang supporting effects of different processed products of Morinda officinalis].

To compare the pharmacological effects for tonifying kidney and supporting Yang of different processed products of Morinda officinalis. The oral administration of adenine was performed to establish the kidney-Yang deficiency mice model. Four different processed products, namely M. officinalis, morinda pulp, salt-steamed M. officinalis and licorice-processed M. officinalis, were administered, with Guifu Dihuang pills as the control drug, and mice signs, weight, testicular coefficient, seminal vesicle coefficient, serum testosterone, serum cortisol and serum creatinine as evaluation indexes. The results showed that all of the four processed products of M. officinalis could improve the symptoms of the kidney-Yang deficient mice. Among them, salt-steamed M. officinalis had the most significant effect, which was followed by licorice-processed M. officinalis, morinda pulp and M. officinalis.

[Effect of electroacupuncture on spleen lymphocyte apoptosis-related gene expression in aging rats with yang deficiency].

OBJECTIVE: To observe effects of electroacupuncture (EA) of "Guanyuan" (GV 4)-"Housanli" (ST 36)-"Baihui" (GV 20,"Shuanggu Yitong" acupoint prescription) on the expression of splenic lymphocyte apoptosis-related genes Fas, Bax, and Bcl-2 in aging rats with yang defiency. METHODS: Thirty Sprague-Dawley aged female rats were randomly and e-ic qually divided into normal control, yang deficiency model (model) and EA groups. The yang deficiency model was established by subcutaneous injection of D-galactose (125 mg/kg) and hydrocortisone(1.5 mg/100 g). EA (2 Hz, 1 mA) was applied to "Guanyuan"(GV 4), "Housanli" (ST 36) and "Baihui" (GV 20) for 15 min, once daily, 6 times per week for 4 weeks. The expression of pro-apoptotic genes Fas, Bax and anti-apoptosis gene Bcl-2 in the spleen tissues were detected by real-time quantitative RT-PCR. RESULTS: In comparison with the normal control group, splenic Fas mRNA and Bax mRNA expression levels were upregulated significantly, and Bcl-2 mRNA expression level was down-regulated considerably in the model group (P < 0. 01). After EA intervention, splenic Fas mRNA and Bax mRNA expression levels were down-regulated markedly, while Bcl-2 mRNA expression up-regulated remarkably in the EA group (P < 0.05, P < 0.01). CONCLUSION: EA of acupoint prescription ["Guanyuan" (GV 4), "Housanli" (ST 36) and "Baihui" (GV 20)] can down-regulate spleen Fas mRNA and Bax mRNA expression, and up-regulate Bcl-2 mRNA expression in aging rats with yang deficiency, which may contribute to its effect in improving yang deficiency in clinic.