Screening of potential biomarkers for Yin-deficiency-heat syndrome based on UHPLC-MS method and the mechanism of Zhibai Dihuang granule therapeutic effect.

BACKGROUND: Yin-deficiency-heat (YDH) syndrome is a subhealth state of the individual, mainly manifested as oral ulcers, dry mouth, constipation, and other symptoms. Zhibai Dihuang granule (ZDG), as a classic traditional Chinese medicine, is effective in treating YDH syndrome. We screened the potential biomarkers for diagnosing YDH syndrome, and explored the mechanisms of the therapeutic effect of ZDG. METHODS: Plasma samples from the Pinghe (PH, healthy control) group, the Shanghuo (SH, YDH syndrome) group, and the ZDG treated group (therapeutic group) were analyzed by using metabolomics profiling. The data were analyzed by multivariate statistical and bioinformatics analyses. RESULTS: We screened four differential metabolites such as, decanoylcarnitine, dodecanoylcarnitine, phosphatidylcholine (PC), and Aspartate (Asp) Arginine (Arg) Proline (Pro) in the SH group and the PH group. The results showed that the combination of above four metabolites could serve as a potential biomarker for the early diagnosis of YDH syndrome. The metabolites decanoylcarnitine and glucose were found to be differentially expressed in the YDH syndrome group and tended to be normalized after ZDG treatment. CONCLUSION: The increased levels of four differential metabolites (decanoylcarnitine, dodecanoylcarnitine, PC, and Asp Arg Pro) revealed that individuals with YDH syndrome may have increased energy metabolism in the body, which could lead to disorders of fatty acids ß-oxidation and immune function. The levels of two differential metabolites including decanoylcarnitine and glucose returned to normal after ZDG treatment, indicating that ZDG could treat YDH syndrome by regulating glucose metabolism and fatty acids ß-oxidation. Our study provides a new method for the diagnosis of YDH syndrome, and may provide theoretical basis for novel therapeutic strategies of YDH syndrome.

A group of serum proteins as potential diagnostic biomarkers for Yin-deficiency-heat syndrome.

Yin-deficiency-heat (YDH) syndrome is a very common subhealth status in Traditional Chinese Medicine. However, currently, there is no unified standard for diagnosing YDH syndrome. We applied the iTRAQ-2D LC-MS/MS method to explore the potential of serum protein profiles as biomarker for YDH syndrome. A total of 120 differentially expressed proteins (79 downregulated and 41 upregulated) were identified by the proteomic profiling. The results of KEGG pathway analysis showed that the functions of the differentially expressed proteins were mainly involved in complement and coagulation cascades. The clinical data showed that YDH syndrome was closely related to inflammation and coagulation, compared with the healthy controls. The ELISA validation results indicated that the expression levels of ALB, CFI, and KLKB1 were downregulated in the YDH syndrome group (p < .05). Moreover, we established a decision tree model based on the combination of these three proteins and achieved a sensitivity of 87.5%, a specificity of 84.4%, and AUC of 0.891. The results indicated that the combination of ALB, CFI, and KLKB1 may serve as potential biomarkers for diagnosing YDH syndrome. Our study can provide a new method for YDH syndrome diagnosis, and may also provide an experimental basis to understand the molecular mechanism of YDH syndrome.

Identification of potential metabolic biomarkers in Yin deficiency syndrome using LC-MS.

Yin and Yang are the two counter-balancing aspects in ancient Chinese philosophy. In traditional Chinese medicine, Yin deficiency syndrome (YDS) is a common sub-health state with complex causes. While the syndrome may be treated to various degrees of effectiveness with traditional Chinese medicine, efficient modern methods are yet to be developed for diagnosing and treating the YDS. Here we performed a metabolomics study on YDS in rats. Serum metabolites in rats were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method to identify potential biomarkers for YDS. The rats were divided randomly into the healthy control group, the untreated YDS group, and the anemarrhena treated YDS group. Compared with the control group, significant increase in the metabolites such as dihydrotestosterone (DHT) and 5ß-DHT, 4-imidazolone-5-propanoate, 4-(L-alanin-3-yl)-2-hydroxy-cis,cis-muconate 6-semialdehyde, and 5-(L-alanin-3-yl)-2-hydroxy-cis,cis-muconate 6-semialdehyde were observed in the serum of untreated YDS group, which returned to normal in the anemarrhena treated group. Therefore, these metabolites may serve as potential biomarkers for YDS, and may facilitate the diagnosis and treatment of YDS.

Plasma metabolic profiling on postoperative colorectal cancer patients with different traditional Chinese medicine syndromes.

OBJECTIVES: This study aims to investigate the metabolic profiles of postoperative colorectal cancer (PCRC) patients with different traditional Chinese medicine (TCM) syndromes and to discuss the metabolic mechanism under PCRC progression and TCM syndrome classification. METHODS: Fifty healthy controls (HC) and 70 PCRC patients, including 10 Dampness and heat syndrome (DHS), 33 Spleen deficiency syndrome (SDS), 19 Liver and kidney Yin deficiency syndrome (LKYDS) and 8 with non-TCM syndrome (NS) were enrolled. Plasma metabolic profiles were detected by Gas chromatography-mass spectrometry (GC-MS) and analyzed by principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA). Furthermore, pathway enrichment was analyzed based on KEGG and DAVID databases and metabolic network was constructed via metaboanalyst and cytoscape. RESULTS: The top-3 metabolites with higher abundance in PCRC compared with HC were terephthalic acid (165.417-fold), ornithine (24.484-fold) and aminomalonic acid (21.346-fold). And the cholesterol (0.588-fold) level was decreased in PCRC. l-Alanine, 1, 2-ethanediamine, urea, glycerol, glycine, aminomalonic acid, creatinine and palmitic acid were specifically altered in the DHS, while d-tryptophan was exclusively changed in SDS, and l-proline, 1, 2, 3-propanetricarboxylic acid, d-galactose and 2-indolecarboxylic acids in LKYDS. CONCLUSIONS: The plasma metabolic profiles were perturbed in PCRC patients. Increased levels of terephthalic acid might indicate high risk of relapse and elevated ornithine may contribute to the post-operational recovery or may raise the susceptibility to PCRC recurrence. The metabolic profiles of DHS, SDS, LKYDS and NS were almost separately clustered, indicating the possibility of explaining TCM syndromes classification using metabolomics. Furthermore, creatinine and aminomalonic acid alternation might correlate with the formation of DHS, while d-tryptophan may associate with SDS and d-galactose and 1, 2, 3-propanetricarboxylic acid may relate to LKYDS. As numbers of patients in each TCM syndrome are small, further study is needed to verify those results.

[Exploration on the treatment of xiaoke in terms of the conception vessel].

Diabetes is in the category of xiaoke in TCM, which is mainly discussed in light of yin deficiency. The conception vessel is the sea of yin meridians, acting on regulating the accumulation and irrigation of qi and blood of twelve meridians and collaterals. The physiological function of the conception vessel is closely related to the pathogenesis of xiaoke, its running course is highly coincident with the location of xiaoke and the symptoms of xiaoke are relevant with the indications of the conception vessel. Hence, harmonizing qi and blood of the conception vessel may be an effective approach to the prevention and treatment of xiaoke.

Characteristics of blood glucose excursions in type 2 diabetes mellitus patients with three different Traditional Chinese Medicine syndromes.

OBJECTIVE: To explore the characteristics of blood glucose excursions of type 2 diabetes mellitus patients with three different Traditional Chinese Medicine (TCM) syndromes. METHODS: One hundred and nine patients with type 2 diabetes mellitus were recruited from the Department of Endocrinology and the Department ***of TCM of the Sixth People's Hospital affiliated to Shanghai Jiao Tong University. Subjects were divided into three groups according to TCM syndrome: intrinsic Damp (n = 42), Yin deficiency and internal Heat (n = 25), and Qi and Yin deficiency (n = 42). Subcutaneous interstitial glucose was monitored with a continuous glucose monitoring system for 3 consecutive days to investigate the glycemic profile in each group. Plasma C-peptide levels were measured, and an arginine test was taken in 10 patients randomly selected from each group. Glucose data and glycemic variability were analyzed to investigate the differences among the groups. The change in C-peptide levels and the results from arginine trial were used to evaluate ß cell function. RESULTS: Indicators reflecting blood glucose level were the highest in subjects with Yin deficiency and internal Heat syndrome, and parameters reflecting glycemic variability were the lowest in those with Qi and Yin deficiency syndrome. The change in C-peptide levels showed that subjects with Qi and Yin deficiency syndrome had the best ß cell function among the three groups; this was confirmed by the arginine trial. CONCLUSION: Patients with Qi and Yin deficiency syndrome had a more stable blood glucose profile, as glycemic variability was higher in those with intrinsic Damp syndrome and those with Yin deficiency and internal Heat syndrome.

An integrated metabonomic and proteomic study on Kidney-Yin Deficiency Syndrome patients with diabetes mellitus in China.

AIM: To investigate specific changes in metabolites and proteins of Kidney-Yin Deficiency Syndrome (KYDS) patients with diabetes mellitus (DM) in China. METHODS: KYDS (n=29) and non-KYDS (n=23) patients with DM were recruited for this study. The KYDS was diagnosed by two senior TCM clinicians separately. The metabonomic and proteomic profiles of the patients were assessed using a metabonomic strategy based on NMR with multivariate analysis and a proteomic strategy based on MALDI-TOF-MS, respectively. RESULTS: Eighteen upregulated peptides and thirty downregulated peptides were observed in the plasma of the KYDS patients. Comparing the proteomic profiles of the KYDS and non-KYDS groups, however, no significantly differentially expressed peptides were found. At the same time, major metabolic alterations were found to distinguish the two groups, including eight significantly changed metabolites (creatinine, citrate, TMAO, phenylalanine, tyrosine, alanine, glycine and taurine). The levels of creatinine, citrate, TMAO, phenylalanine and tyrosine were decreased, whereas the levels of alanine, glycine and taurine were increased in the KYDS patients. These biochemical changes were found to be associated with alterations in amino acid metabolism, energy metabolism and gut microflora. CONCLUSION: The identification of distinct expression profiles of metabolites and signaling pathways in KYDS patients with DM suggests that there are indeed molecular signatures underlying the principles of 'Syndrome Differentiation' in traditional Chinese medicine.

[Differentially expressed proteins in serum among different Chinese medical syndrome types of primary liver cancer in the perioperative period of interventional treatment].

OBJECTIVE: To explore different expressions of serum proteins among different Chinese medical syndrome types of primary liver cancer (PLC) in the perioperative period of interventional treatment, and to explore its significance. METHODS: Totally 154 PLC patients were assigned to Gan depression syndrome (GDS, 37 cases), Pi deficiency syndrome (PDS, 45 cases), dampness heat syndrome (DHS, 18 cases), blood stasis syndrome (BSS, 28 cases), and yin deficiency syndrome (YDS, 26 cases). The mass spectra of serum proteins were analyzed by using surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS). By combining the features of Chinese medical syndromes, the different expressions of serum proteins among different Chinese medical syndrome types of PLC in the perioperative period of interventional treatment were explored. RESULTS: One week before interventional treatment, there was statistical difference in the expression of serum protein peak with mass-to-charge ratio (M/Z) being 3,392, 4,970, 5,911, 6,200, and 8,575 Da (P <0.05, P < 0.01). The aforesaid differentially expressed protein peaks occurred simultaneously in PDS and BSS. One week after interventional treatment, the expression of the serum protein peak was down-regulated in YDS syndrome with M/Z being 8,575 Da, showing statistical difference (P <0.01). CONCLUSION: Different peaks of serum proteins occurred in different Chinese medical syndrome types of PLC in the perioperative period of interventional treatment.

Discrimination of type 2 diabetes mellitus corresponding to different traditional Chinese medicine syndromes based on plasma fatty acid profiles and chemometric methods.

AIMS OF THE STUDY: Traditional Chinese medicine (TCM) has a long history and particular advantages in the diagnosis and treatment of type 2 diabetes mellitus (T2DM). Syndrome differentiation is the foundation and essence of TCM theories. The aims of the study are to discriminate T2DM corresponding to different syndromes (Qi-deficiency, Qi and Yin-deficiency and Damp heat) and discover syndrome-related biomarkers using metabolomics technology. MATERIALS AND METHODS: Plasma fatty acid profiles of 85 clinical samples were established by high performance liquid chromatography (HPLC). Moreover, some of the lipid parameters, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), were obtained through clinical testing methods. Orthogonal signal correction-partial least squares (OSC-PLS) and uncorrelated linear discriminant analysis (ULDA) were employed to establish two-class models for three different syndromes. RESULTS: Compared with the plasma fatty acid profiles of healthy controls, the characteristic fatty acids of three TCM syndromes were discovered (p<0.01). Totally, the plasma fatty acids of T2DM were up-regulated, while significant differences existed in different syndromes. Results of ULDA indicate that the three TCM syndromes could be effectively separated by the plasma fatty acid profiles and the syndrome-related biomarkers were also screened. CONCLUSIONS: The fact that three TCM syndromes can be separated indicates certain metabolic differences in different TCM syndromes of T2DM really exist and such differences can be manifested by fatty acids and lipid parameters. The results benefit modern biological interpretation of the three TCM syndromes and in a sense the diagnosis and treatment of diabetes.

Analysis of plasma proteome from cases of the different traditional Chinese medicine syndromes in patients with chronic hepatitis B.

A proteomic analysis method, two dimensional gel electrophoresis (2-DE) followed by matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF-MS), was used to explore the link between plasma proteome and the different syndromes of traditional Chinese medicine (TCM) in patients with chronic hepatitis B (CHB). In compared with the plasma proteomes from health donors, the alterations in protein expression from cases of the five TCM syndromes, including damp heat stasis in the middle-Jiao syndrome, liver Qi stagnation and spleen deficiency syndrome, spleen and kidney Yang deficiency syndrome, liver and kidney Yin deficiency syndrome, and blood stasis into collateral syndrome with CHB were identified (P<0.05). In the cases of the five TCM syndromes with CHB, immunoglobulin J-chains (IGJ) and C-reactive protein (CRP) were up-regulated, while haptoglobin (HPT), retinol binding protein (RBP) and vitronectin were down-regulated. To further confirm these results, four proteins, including CRP, IGJ, HPT and RBP, from more plasma samples were quantified by ELISA. The results showed that the changes of protein levels were consistent with those from the 2-DE experiment. Importantly, the upregulation tendency of IGJ level in plasma is related with the different TCM syndromes with CHB (P<0.05). Our results show that IGJ may serve as a novel potential biomarker for diagnosis of the different TCM syndromes in patients with CHB.

[Nourishing-yin effect and mechanism of different parts of Cornu Elaphuri Davidiani in rats].

OBJECTIVE: To investigate nourishing-yin effect and mechanism of different parts of Cornu Elaphuri Davidiani in rats. METHOD: The model of yin asthenia rats was built by thy roxine. The substance metabolism, pain threshold, hormone levels and biochemical indicators in serum were measured. RESULTS: The ethanol extract of Cornu Elaphuri Davidiani could regulate the substance metabolism and raise the pain threshold in yin asthenia model rats. Furthermore, it could regulate the hormone levels, biochemical indicators in serum and it could improvte the antioxidant ability. CONCLUSION: The ethanol extract of Cornu Elaphuri Davidiani showed significant nourishing-yin effect in rats and the possible mechanism is correlated with regulating the neuroendocrine network.

[Basic pathogenesis of asthenia of healthy energy and blood stasis in liver cirrhosis studied by serum proteomics].

OBJECTIVE: To study the basic pathogenesis of "asthenia of healthy energy and blood stasis" in liver cirrhosis studied by Chinese syndromes and serum proteomics. METHODS: The information of four methods of examinations and serum samples were collected from 44 cases of male cirrhotic patients and 17 cases of healthy male volunteers. The different syndrome groups were summarized according to syndrome differentiation and frequency analysis using the patient's information of four methods of examinations. The serum proteins were isolated by magnetic beads and detected by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The proteins expressed differently between cirrhotic patients of different syndrome types and healthy volunteers were analyzed by statistical analysis software (product of Bruker Corporation ClinProTools 2.1 software). The diagnosis model was established by QC algorithm. RESULTS: The liver cirrhosis syndrome with the appearance frequency of more than 30% was sequenced from high to low as fatigue, listlessness, spider telangiectasia, liver palms, anorexia, bleeding from the nose, the gum or the subcutaneous tissue, the abdominal distention, shortness of breath while moving, dim facial complexion, pricking pain of the flank, weak waist and knees, dull pain in the flank, burning sensation of five centers, or low fever, hectic fever, and night sweat. The cases belonging to Child-Pugh A in the seventeen patients of the Pi-qi asthenia syndrome group accounted for 64.7%. The cases belonging to Child-Pugh C in the twelve patients of the Gan-Shen yin deficiency syndrome group accounted for 66.7%. The cases belonging to Child-Pugh A were similar to the cases belonging to Child-Pugh C in the fifteen patients of the blood stasis syndrome group, being more than 40%. Such syndromes as spider telangiectasia, liver palms, shortness of breath while moving, burning sensation of five centers, or low fever, hectic fever, and night sweat, varicose vein of the abdominal wall, and edema of lower extremities appeared more frequently in Child-Pugh C than in Child-Pugh A (all P < 0.05). The characteristic protein expression peak with mass-to-charge ratio of 4642.81, 4963.91, 5247.8, 5805.95, 6305.27, and 12447.7 in the Pi-qi asthenia syndrome diagnosis model were chosen. The former five peaks could be found in Child-Pugh A and Child-Pugh C. The protein expression peak with mass-to-charge ratio of 9 290. 3 was the characteristic protein expression peak in the Gan-Shen yin deficiency syndrome diagnosis model. The protein expression peak with mass-to-charge ratio of 9290.06 and 7 768. 29 were down-regulated in the Gan-Shen yin deficiency syndrome group compared with the other two syndromes groups. The protein expression peaks 9290.3 and 7768.29 were included in the diagnosis model of hepatitis B cirrhosis. They did not appear in Child-Pugh A, while they were gradually down-regulated in Child-Pugh B and Child-Pugh C. Of the other seventeen protein expression peaks in patients of the Gan-Shen yin deficiency syndrome, eight expressed in Child-Pugh A. The protein expression peaks 4964.55 and 5806.83 that expressed both in Child-Pugh A and Child-Pugh C constituted the characteristic protein peaks of the hepatitis B cirrhosis blood stasis diagnosis model. The diagnosis model of the Pi-qi asthenia syndrome was established with the sensitivity of 100% and the specificity of 82.35%. The diagnosis model of the Gan-Shen yin deficiency syndrome was established with the sensitivity of 100% and the specificity of 94.12%. The diagnosis model of the blood stasis syndrome was established with the sensitivity of 100% and the specificity of 100%. CONCLUSIONS: Asthenia of healthy energy and blood stasis was the basic pathogenesis during the whole process of liver cirrhosis. Asthenia of healthy energy covers Pi-qi asthenia and Gan-Shen yin deficiency. Gan-Shen yin deficiency was obvious in the compensation stage of liver cirrhosis, but it has manifested in this stage. So early treatment was necessary.

[Experimental study on Qi deficiency and blood stasis induced by muti-factor stimulation in rats].

OBJECTIVE: Animal model of Qi deficiency and blood stasis was established by muti-factor stimulation in rats. METHOD: Healthy SD rats were chronically stimulated randomly by muti-factor methods (chronic sleep deprivation and feed with moderately high lipid and sugar food). Then the indices of hemorheology, plasma total lipids, vasoactive molecules, blood pressure (BP) and ventricular pressure (VP) were measured. RESULT: The results as well as the analysis of etiology and pathology suggested that model rats could objectively reflect the clinical characteristics of Qi deficiency and blood stasis syndrome. Blood viscosity at low level, plasma content of angiotensin II (Ang II) and endothelin (ET) significantly increased in model rats, while BP and VP significantly decreased (P < 0.05). On the other hand, Buyang Huanwu decoction could lower down the level of AngII in serum and blood viscosity at low level in rats induced by some stimulus, whereas BP and VP elevated significantly (P < 0.05). CONCLUSION: Animal model of Qi deficiency and blood stasis induced by muti-factor stimulation including chronic sleep deprivation and feed with moderately high lipid and sugar food could facilitate further study on blood stasis syndrome and screening of Chinese herbal drugs in promoting blood circulation and removing blood stasis.

Multi-central clinical research into treating 80 cases of chronic thrombocytopenia with qi-supplementing and yin-nourishing therapy and western medicine.

OBJECTIVE: To probe the effects of qi-supplementing and yin-nourishing therapy (blood-increasing decoction and blood generating powder) on chronic thrombocytopenia. METHODS: Two hundred patients with chronic thrombocytopenia were randomly divided into control (n = 100) and test groups (n = 100) with Amino-polypeptide as a basic treatment for both. Test group patients consumed a blood-increasing decoction and blood-generating powder for 1-3 months. Improvements in platelet counts and TCM syndrome were observed. RESULTS: One hundred and sixty-four (80 in the test group and 84 in the control group) of 189 total participants were treated for 3 months. The total effective rate in improving TCM syndrome was 95.00% in the test group and 79.76% in the control group (P < 0.05). There was significant difference (P < 0.05) in the accumulated score of TCM syndrome between the two groups treated at different time points. The total effective rate of platelet counts was 86.25% in the test group and 59.52% in the control group (P < 0.05). There was a significant difference in platelet counts before and after treatment in the two groups (P < 0.05). There was no significant differences in platelet count between the two groups treated for 1-2 months; however, a significant difference was found between the two groups after treatment for 3 months (P < 0.05). CONCLUSIONS: After a 3-month treatment of chronic thrombocytopenia patients with qi-supplementing and yin-nourishing therapy, TCM syndrome was improved and platelet counts increased with no obvious side effects, and the quality of life of the participants was enhanced with noticeable long-term curative effects.

Effect of Yinian Jiangya Yin on primary hypertension in early stage--a clinical observation on 40 patients.

OBJECTIVE: To observe the effect of Yinian Jiangya Yin (Decoction for lowering blood pressure to prolong life) on patients with early hypertension and its mechanism on the function of vascular endotheliocytes. METHODS: The 79 patients with early primary hypertension belonging to the TCM syndrome of stagnation of phlegm and blood stasis in meridians and hyperactivity of the liver-yang were randomly divided into a treatment group of 40 patients treated with Yinian Jiangya Yin and a control group of 39 patients treated with Tianma Gouteng Yin (Decoction of Gastrodia and Uncaria). The changes in score of TCM syndrome and in blood pressure before and after treatment were observed in the two groups. The contents of nitrogen monoxide (NO) and endothelin (ET) in serum after treatment were determined. RESULTS: There was a statistical difference (P < 0.05) in score of TCM syndrome, effect of lowering blood pressure, and the contents of ET and NO in serum after treatment between the two groups. CONCLUSION: The effect of Yinian Jiangya Yin on improving TCM syndrome of patients with primary hypertension in early stage and on lowering blood pressure may be related to its regulating the imbalanced condition between ET and NO for restoring the function of endothelium-dependent vasodilation.

Clinical observation on the endocrinal and immune functions in subjects with yin-deficiency constitution.

OBJECTIVE: To explore the relationship between yin-deficiency constitution (YDC) and biochemical indexes by way of observing the endocrinal and immune functions in subjects with YDC. METHODS: On the basis of epidemiological investigation, 60 subjects with YDC and 50 with gentle constitution (GC) were selected according to the pertinent criteria. From each subject, 8 mL of fasting venous blood was drawn at 8:00-9:00 in the morning, with the serum separated by centrifugation 3 000 r/min for 5 min and preserved at -70 degrees Celsius in a freezer. Serum levels of corticosterone, cortisol, adrenocorticotrophic hormone (ACTH), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), free triiodothyronine (FT3), free thyroxine (FT4), throtropic stimulation hormone, interleukin 1beta (IL-1beta) and interleukin 2 (IL-2) were detected by double-antibody sandwich ELISA; cAMP/cGMP ratio was calculated, and the difference between the two constitutions in terms of these indexes was analyzed. RESULTS: Serum FT3 was 4.16 + or - 1.38 pmol/L in subjects with YDC, which was higher than that in subjects with GC (3.71 + or - 0.55 pmol/L), but levels of cortisol (124.58 + or - 45.36 ng/mL), ACTH (58.92 + or - 14.55 pg/mL), cGMP (66.00 + or - 18.02 pmol/mL) and FT4 (12.33 + or - 3.12 pmol/L) in YDC were lower than those in GC (13.43 + or - 2.31 pmol/L), showing significant difference (P<0.05). CONCLUSION: YDC is related to some extent with the disturbances in the hypothalamus-pituitary-adrenal axis, hypothalamus-pituitary-thyroid axis, cyclic nucleoside system and immune function.

[Relationship between Chinese medicine pattern with blood levels of sex hormone, lipid and glucose in climacteric women patients with hypertension].

OBJECTIVE: To find the objective indices for traditional Chinese medicine (TCM) pattern identification in women patients with climacteric hypertension (CH) by exploring the relationship between TCM pattern with blood levels of sex hormone, lipid and glucose. METHODS: TCM syndrome differentiation was made in 75 women CH patients, 43 as yin-deficiency with inner dryness pattern (YDD) and 32 as non-YDD, and correlation analyses were conducted on TCM patterns and blood levels of estradiol (E2), lipids and glucose. RESULTS: Besides the level of E2 in YDD was lower than that in non-YDD [(112.26 -/+ 66.81) pmol/L vs (146.69 +/- 83.59) pmol/L, P < 0.05), no difference between the two patterns was found in the other indices measured (P > 0.05). Further subunit analysis showed that in patients with CH grade 1, blood levels of total cholesterol (TC), high density lipoprotein (HDL) and apoprotein A-I (ApoA-I) were higher in the 13 patients of YDD than those in the 9 of non-TDD (P < 0.05); in patients with CH grade 2, levels of E2, progesterone (T), HDL and ApoA-I were lower but level of follicle stimulating hormone (FSH) was higher in the 20 YDD than those in the 10 non-YDD (all P < 0.05); while in patients with CH grade, no statistically significant difference was shown between 3 patients of 10 with YDD and 13 with non-YDD in all the indices measured (P > 0.05). CONCLUSION: Blood level of E2 shows different characteristics between CH patients of YDD and non-YDD patterns, suggesting that it may provide some help to syndrome micro-differentiation, and taking it as an objective index for syndrome typing of climacteric hypertension in female is considerable.

[Expression of TNF-alpha signaling adapter proteins in peripheral blood mononuclear cells in lupus nephritis patients of different TCM asthenia syndromes].

OBJECTIVE: To investigate the mRNA expressions of the TNF adapter proteins, including TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor-interacting protein 1 (RIP-1) and TNF receptor-associated factor-2 (TRAF-2) in peripheral blood mononuclear cells (PBMCs) of lupus nephritis (LN) patients of various TCM asthenia syndromes. Methods Fifty-one inpatients with LN were differentiated according to TCM syndrome differentiation, 13 cases of yin-deficiency with inner heat syndrome (A); 26 cases of both qi-yin deficiency syndrome (B), 12 cases of Pi-Shen yang-deficiency syndrome (C). Peripheral venous blood samples from the 51 LN patients and 17 healthy subjects were collected to separate PBMCs. The mRNA expressions of TNF adapter molecules (TRADD, FADD, RIP-1 and TRAF-2), as well as Caspase-3 and interleukin-1beta (IL-1beta) were analyzed by quantitative real-time PCR and the differences among them were compared. RESULTS: (1) As compared with the healthy subjects, expression of TRADD mRNA in patients of syndrome A, B and C was lowered to 0.54, 0.32, and 0.38-fold, respectively (P < 0.05, P < 0.01), showing insignificant difference among the three syndromes; (2) FADD mRNA lowered to 0.79, 0.62, and 0.72-fold respectively, only with significance shown in syndrome B (P < 0.05); (3) RIP-1 mRNA lowered to 0.79, 0.50, and 0.60-fold respectively with significance shown in syndrome B and C (P < 0.01, P < 0.05), and insignificant difference was shown among the three syndromes; (4) TRAF-2 lowered to 0.70, 0.52, and 0.50-fold respectively (P < 0.01, P < 0.01, P = 0.07), significance shown in syndrome B and C (P < 0.01), but with insignificant difference among the three; (5) Caspase-3 elevated in all patients of the three syndromes (all P < 0.01); (6) IL-1beta in syndrome A was apparently lower ed to the normal range and also lower than that in the other two syndromes (both P < 0.05). CONCLUSIONS: Expressions of TRADD, FADD, RIP-1 and TRAF-2 mRNA decreased in all the patients of various TCM asthenia syndromes, the decrement in patients of syndrome B and C was lesser than that in syndrome A. These abnormal low expressions of signal proteins might be the substantial bases for asthenia syndromes of LN patients, and the apoptotic signal mediated by them may involve in the formation of asthenia syndrome in LN.

[Relationship between plasma protein expression profiles and states of Zang-Fu organs in patients with phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis].

OBJECTIVE: To investigate the relationship between the plasma biomarker proteins and the states of Zang-Fu organs in patients with phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis. METHODS: The states of Zang-Fu organs in 146 patients with hyperlipidemia and atherosclerosis were diagnosed by syndrome differentiation of traditional Chinese medicine. The plasma proteins from these patients were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE). Differential protein profiling was established by Image Master 6.0 software, and the differential proteins were analyzed by quadrupole time of flight mass spectrometry (Q-TOF-MS). The association between the plasma biomarker proteins and the states of Zang-Fu organs was analyzed by graphical models. RESULTS: The biomarker proteins such as fibrinogen gamma chain, albumin and apolipoprotein AI (precursor) in discrimination of the patients with phlegm syndrome from phlegm accumulating with stagnation syndrome were correlated with the deficiency of kidney-qi, heart-qi and spleen-qi. Among the four biomarker proteins in discrimination of the patients with phlegm syndrome from blood stagnation syndrome, albumin, adrenomedullin binding protein (precursor) and haptoglobin (precursor) were correlated with the deficiency of kidney-qi and heart-qi, but complement component C4 was independent of the deficient Zang-Fu organs. The biomarker albumin was associated with the deficiency of kidney-qi, heart-qi and spleen-qi, and adrenomedullin binding protein (precursor) was correlated with the deficiency of spleen-qi in discrimination of the patients with blood stagnation syndrome from phlegm accumulating with stagnation syndrome. As the potential biomarker proteins in discrimination of the patients with non-phlegm and non-stagnation syndrome from phlegm accumulating with stagnation syndrome, the fibrinogen beta chain was related with the deficiency of kidney-qi, and apolipoprotein AI (precursor) was correlated with both the deficiency of kidney-qi and heart-qi. CONCLUSION: There exists inherent correlation between the states of Zang-Fu organs and the plasma probable biomarker proteins in the patients with different phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis.

[The effect of gengnianningshentang on treating 72 patients with female climacteric syndrome of fever due to yin-deficiency].

OBJECTIVE: To observe the clinical effect of gengnianningshentang on the treatment of the climacteric syndrome of fever due to yin-deficiency. METHODS: 108 patients with climacteric syndrome of fever due to yin-deficiency were divided randomly into treatment group (76 cases)and control group (32 cases). Treatment group was treated by gengnianningshentang, and control group was treated by Vitamin E for 3 months. Level of serum E2, LH and FSH were determined, while the variation of symptom scores of climacteric syndrome was observed. RESULTS: Level of serum E2 in treatment group increased significantly and serum LH and FSH decreased significantly after treatment (p < 0.01). The post treatment total scores of climacteric syndrome in the treament group were significantly improved (p < 0.01). CONCLUSION: Gengnianningshentang can significantly improve the levels of E2, FSH and LH, and climacteric syndrome in patients of fever due to yin-deficiency. The total effect of gengnianningshentang is much better than western medicine.