Study on blood pressure rhythm in hypertensive patients withdeficiency syndrome and a random forest model for predicting hypertension withdeficiency syndrome.

OBJECTIVE: To investigate blood pressure rhythm (BPR) in Yin deficiency syndrome of hypertension (YDSH) patients and develop a random forest model for predicting YDSH. METHODS: Our study was consistent with technical processes and specification for developing guidelines of Evidence-based Chinese medicine clinical practice (T/CACM 1032-2017). We enrolled 234 patients who had been diagnosed with primary hypertension without antihypertensive medications prior to the enrollment. All participants were divided into Yin deficiency group (YX, n = 74) and non-Yin deficiency group (NYX, n = 160). Participants were professionally grouped by three experienced chief Traditional Chinese Medicine (TCM) physicians according to four examinations (i.e., inspection, listening and smelling, inquiry and palpation). We collected data on 24 h ambulatory blood pressure monitoring (ABPM) and YDSH rating scale. We divided 24 h of a day into 12 two-hour periods [Chen-Shi (7:00-9:00), Si-Shi (9:00-11:00), Wu-Shi (11:00-13:00), Wei-Shi (13:00-15:00), Shen-Shi (15:00-17:00), You-Shi (17:00-19:00), Xu-Shi (19:00-21:00), Hai-Shi (21:00-23:00), Zi-Shi (23:00-1:00), Chou-Shi (1:00-3:00), Yin-Shi (3:00-5:00), Mao-Shi (5:00-7:00)] according to the theory of "midnight-midday ebb flow". We used random forest to build the diagnostic model of YDSH, with whether it was Yin deficiency syndrome as the outcome. RESULTS: Compared with NYX group, YX group had more female participants with older age, lower waist circumference, body mass index (BMI), diastolic blood pressure (DBP), and smoking and drinking rate (all P ＜ 0.05). The YDSH rating scores of YX group [28.5 (21.0-36.0)] were significantly higher than NYX group [13.0 (8.0-22.0)] (P < 0.001), and the typical symptoms of YX group included vexing heat in the chest, palms and soles, dizziness, dry eyes, string-like and fine pulse, soreness and weakness of lumbus and knees, palpitations, reddened cheeks, and tinnitus (all P < 0.05). The ratio of non-dipper hypertension in YX group was higher than in NYX group (56.9% vs 44.4%, P = 0.004). Compared with NYX group, 24 h DBP standard deviation (SD), nighttime DBP SD, Si-Shi DBP, Si-Shi mean arterial pressure (MAP), Hi-Shi systolic blood pressure (SBP), Hi-Shi DBP, Hi-Shi MAP, Zi-Shi SBP, Zi-Shi DBP, Zi-Shi MAP, Chou-Shi SBP SD, Chou-Shi DBP SD, Chou-Shi SBP coefficient of variation (CV) were lower in YX group (all P ＜ 0.05). Binary Logistic Regression analysis showed that the diagnosis of YDSH was positively correlated with age, heart rate, YDSH rating scores, and four TCM symptoms including vexing heat in the chest, palms and soles, string-like and fine pulse, soreness and weakness of lumbus and knees, and reddened cheeks (all P ＜ 0.05), but was negatively correlated with smoking (P﹥0.05). In addition, the diagnosis of YDSH was positively correlated with daytime SBP SD, nighttime SBP SD, nighttime SBP CV, and Hi-Shi SBP CV, but was negatively correlated with 24 h SBP CV, daytime DBP SD, nighttime DBP SD, and Hi-Shi DBP (all P ＜ 0.05). Hi-Shi SBP CV had independent and positive correlation with the diagnosis of YDSH after adjusting the variables of age, gender, course of hypertension, BMI, waist circumference, SBP, DBP, heart rate, smoking and drinking (P = 0.029). Diagnostic model of YDSH was established and verified based on the random forest. The results showed that the calculation accuracy, specificity and sensitivity were 77.3%, 77.8% and 76.9%, respectively. CONCLUSION: The BPR was significantly attenuated in YDSH patients, including lower 24 h DBP SD and nighttime DBP SD, and Hi-Shi SBP CV is independently correlated with the diagnosis of YDSH. The prediction accuracy of diagnosis model of YDSH based on the random forest was good, which could be valuable for clinicians to differentiate YDSH and non-Yin deficiency patients for more effective hypertensive treatment of TCM.

[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.

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.

Gene expression profiling of rat livers with yin-deficiency-heat syndrome.

OBJECTIVE: To explore the nature of "Yin internal heat caused by Yin-deficiency," in terms of the theory of Traditional Chinese Medicine, by studying energy metabolism in rats with Yin-deficiency-heat syndrome and analyzing the gene expression profile of their livers. METHODS: A Yin-deficiency-heat syndrome model was induced in rats using three Chinese medicinal herbs. Glycogen and triglycerides in blood plasma, and the enzyme activity of ATP in livers were measured colorimetrically. Triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone levels in blood plasma were also measured with enzyme linked immunosorbent assay. The gene expression profile of livers was detected with gene chip analysis. Differentially expressed genes were screened out and classified according to Gene Ontology. The accuracy of results were examined with reverse transcription-polymerase chain reaction. RESULTS: Compared with the control group, body weight (P < 0.05) and hepatic glycogen (P < 0.05) were significantly lower in the Yin-deficiency-heat syndrome group. Moreover, toe temperature (P < 0.01) and triglyceride (P < 0.05), Na(+) -K(+)-ATPase (P < 0.01), Mg(2+)-ATPase (P < 0.01), T3 (P < 0.05), and T4 (P < 0.01) levels were significantly higher. There were 99 differentially expressed genes in livers from the Yin-deficiency-heat syndrome group. Genes were mainly related to sterol synthesis (Pc = 0.0392), defense response (Pc = 0.0448), and sterol metabolism (Pc = 0.0533). CONCLUSION: Abnormal expression genes in rats with Yin-deficiency-heat syndrome prompted the synthesis and metabolism of cholesterol, increased energy consumption, and reduced defense response. This gene expression might be the molecular mechanism underlying "internal heat caused by Yin-deficiency" in the rats with Yin-deficiency-heat syndrome.

Increased yin-deficient symptoms and aggravated autonomic nervous system function in patients with metastatic cancer.

OBJECTIVES: The objectives of this study were to investigate the differences in severity of yin-deficiency syndrome (YDS) and function of the autonomic nervous system (ANS) between patients with cancer with metastasis and those without metastasis. SETTING: The setting was an outpatient clinic in a teaching hospital in central Taiwan. SUBJECTS: The subjects were a total of 124 patients who had been diagnosed with cancer on the basis of pathologic and clinical findings. Among them, 61 had distant metastasis, and the other 63 had no evidence of metastasis. The two groups were similar in terms of age and gender. INTERVENTIONS: The severity of YDS in each subject was evaluated using a questionnaire containing 12 items about symptoms and signs related to YDS. The severity of each symptom or sign was rated on a 4-point scale. OUTCOME MEASURES: The total score on the questionnaire represented the severity of YDS. ANS function in each subject was evaluated by measuring heart rate variability (HRV), including time and frequency domains. The questionnaire data were coded, and statistical analysis was performed using SPSS version 12.0. Data were analyzed using the Student's t test or the χ(2) test. RESULTS: The patients with metastasis had significantly higher average total YDS score and heart rate compared with the patients without metastasis. In contrast, they had significantly lower HRV, including standard deviation of the 5-minute average R-R interval, total power, very-low-frequency power, and low frequency (LF) power, but not high-frequency (HF) power and LF/HF ratio. CONCLUSIONS: The results of this study indicate that patients with metastatic cancer have more severe YDS and impaired ANS function than those without metastasis.

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.

Comfortable lifestyle-induced imbalance of neuro-endocrine-immunity network: a possible mechanism of vascular endothelial dysfunction.

OBJECTIVE: To observe the changes of vascular endothelial functions and general neuro-endocrine-immunity (NEI) network under the state of qi-deficiency syndrome induced by excessive idleness and to approach their internal relevance and illuminate initially the pathophysiological mechanism of vascular lesion induced by excessive idleness. METHODS: A total of 100 male Wistar rats were randomly divided into the control group and the qi-deficiency syndrome model group, 50 rats in each group. The qi-deficiency syndrome model was established by feeding the animals with hyper-alimentation diet in combination with restricting movement for 10 weeks. Changes of common chemical signal molecules related to NEI and vascular endothelial functions were measured by the end of the experiment. Furthermore, their internal relevance was analyzed by the method of canonical correlation analysis. RESULTS: The vascular endothelial structure and function were obviously injured in the model group. Compared with the control group, the chemical signal molecules, such as 5-hydroxytryptamine (5-HT), corticosterone (CORT), triiodothyronine (T3), tetraiodothyronine (T4), angiotensin II (Ang II), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) in peripheral blood of the model group (n=43) were changed significantly (P<0.05 or P<0.01). Canonical correlation analysis showed that vascular endothelial dysfunction was correlated to the changes of these signal molecules in the NEI network. CONCLUSIONS: Comfort-based lifestyle induced not only vascular endothelial dysfunction but also an imbalance of the NEI network. Vascular endothelial dysfunction and the imbalanced NEI network interacted with each other, and an imbalance of the NEI network may be the pathophysiologic basis for the genesis and development of vascular endothelial dysfunction, even diseases of the blood vessel.

Severity of Yin deficiency syndrome and autonomic nervous system function in cancer patients.

OBJECTIVE: To evaluate the distribution of symptoms related to Yin deficiency syndrome (YDS), and to analyze the relationship between the severity of YDS and the function of the autonomic nervous system (ANS) in cancer patients. SETTING: Outpatient clinic in a teaching hospital in central Taiwan. SUBJECTS: Eighty (80) patients had been diagnosed with cancer by pathologic and clinical findings. METHOD: The severity of YDS in each subject was evaluated by a questionnaire consisting of 12 items concerning symptoms and signs related to YDS, scored from 1 to 4 points. OUTCOME MEASURES: The total score for all 12 items represented the severity of YDS. ANS function in each subject was evaluated by measuring heart rate variability (HRV), including time-frequency analysis. We coded the collected questionnaire material and performed statistical analysis (description analysis, ANOVA, and Pearson's correlation coefficients) using SPSS v.12.0 software. RESULTS: The highest total YDS score was 36 points and the lowest was 10 points. The 3 most common YDS signs were dry mouth (58.8%), sleeplessness with annoyance (56.3%), and flush over face in the afternoon (22.5%). The total YDS scores had a significantly positive correlation with heart rate (HR), but had significantly negative correlation with the standard deviation of the 5-minute mean R-R intervals (SDANN), total HRV power, power in the very low frequency band, and in the low frequency band. CONCLUSIONS: The above results suggest that the severity of YDS in cancer patients was associated with increased HR and decreased ANS activity. There is a possibility that the disturbance of ANS function may contribute to the occurrence of YDS in cancer patients.

The distribution of Yin-Deficient symptoms and their relationship on survival rate in cancer patients with Yin-Deficiency.

Yin-Deficiency (YD), representing a status of the human body under lack of nutrition and fluid in traditional Chinese medicine, is commonly seen in late stage of cancer patients. It is not known whether the severity of YD related symptoms/signs can predict the survival rate of cancer patients. This study evaluated the distribution of Yin-deficiency symptoms/signs (YDS) in cancer patients with YD, and investigated whether the severity of YDS can predict the survival rate of cancer patients with YD. From 5 January 2007 to 5 May 2007, we selected 43 cancer patients with diagnosis of YD from hospitalized patients and outpatients. The severity of YD was evaluated by a questionnaire. We further estimated the cumulative probabilities of the survival rates over 4 months since the start of study by the Kaplan-Meier product-limit method, and compared the differences among groups with various severities in each symptom/sign with the use of the log-rank test. The results revealed that, the 3 most common YDS were sleeplessness with annoyance, less or non-coated tongue with or without redness and dry mouth. In the survival rate analysis, only 2 parameters, rapidly small pulse (p = 0.002) and less-or non-coated tongue with paleness (p = 0.017), were found to be related to the decrease of cancer patients with YD. This suggests that, both rapidly small pulse and less-or non-coated tongue without redness may be used as predictors for the estimation of survival rate in cancer patients with YD.

[Observation on effects of Zhiling Capsule in treating 400 patients with various types of cancer in mid-ad-vanced stage].

OBJECTIVE: To observe the efficacy of Zhiling Capsule (ZLC) in improving symptoms and quality of life (QOL) in patients with various types of cancer in mid-advanced stage. METHODS: A multi-centre randomized and controlled trial was conducted. Four hundred patients with mid-advanced cancer were assigned to two groups: the treatment group (300 cases) treated with ZLC and the control group (100 cases) with Pingxiao Capsule (PXC), both were given orally for two weeks. Clinical symptoms, QOL, weight and adverse reactions were observed before and after treatment. RESULTS: Improving rate of symptom, increasing rates of QOL and weight in the treatment group were all higher than those in the control group (P<0.05); and no obvious adverse reaction was observed in the two groups. CONCLUSION: ZLC could alleviate the qi-yin deficiency syndrome and pain syndrome and improve QOL in patients with various types of cancer in mid-advanced stage.

[Effect of regulation of kidney-yin and kidney-yang on hypothalamus-pituitary-adrenal-thymus axis in monosodium L-glutamate rats].

OBJECTIVE: To study the interrelationship between hypothalamus-pituitary-adrenal-thymus (HPAT) axis and Kidney-Yang and Kidney-Yin in arcuate nucleus destroyed rats. METHODS: Monosodium glutamate (MSG) 4 mg/g body weight was given subcutaneously to neonatal rats at 2, 4, 6, 8 and 10th day after born to destroy the ARC, and Zuogui pill or Yougui pill (5 g/kg daily) was given respectively by gastrogavage when the model rats entered adulthood. RESULTS: Immunohistochemical staining showed that in the model group the number of corticotropin-releasing hormone (CRH) positive neurons in hypothalamic paraventricular nucleus and anterior pituitary adrenotrophin (ACTH) positive secretory cells, which stained deeply, were more than those in the control group, the adrenal fasciculate zone disturbed with increased cells and obviously dilated sinusoid. The thymus atrophied with lymphocyte proliferation apparently lower, blood corticosterone, ACTH content and hypothalamic CRF level higher in the model than those in the control. Zuogui pill could improve above-mentioned pathophysiologic changes effectively but Yougui pill could not. CONCLUSION: Process of pathophysiology of HPA axis hyperfunction accompanied cell-mediated immunodeficiency may belong to the category of Kidney-Yin Deficiency Syndrome.