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Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).
Subject(s)
Ovarian Reserve , Yin Deficiency , Humans , Yin Deficiency/drug therapy , Yang Deficiency/drug therapy , Syndrome , Proteinuria , BiomarkersABSTRACT
Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).
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ObjectiveTo investigate the effects of spleen-Yin deficiency on gastrointestinal absorption， water metabolism and intestinal flora in rats with spleen-Yin deficiency syndrome. MethodA rat model of spleen-Yin deficiency syndrome was established by using the composite factors， including irregular meat and vegetable diet， weight-bearing fatigue swimming and gavage with warm-heat injury-Yin drugs. The changes of body weight， food intake， water intake and duration of swimming in the blank and model groups were observed. Hematoxylin-eosin（HE） staining was used to observe the histopathological damage of the stomach and colon. Urinary excretion rate of D-xylose was determined by phloroglucinol method. The content of gastrin（GAS） in serum was determined by enzyme-linked immunosorbent assay（ELISA）. The relative expression levels of vasoactive intestinal peptide（VIP）， aquaporin 3（AQP3） and AQP4 in gastric tissues were detected by Western blot. The relative mRNA expression levels of VIP， AQP3 and AQP4 in gastric tissues were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the changes of intestinal flora were analyzed by 16S rDNA sequencing. ResultCompared with the blank group， the results of general physical signs showed that the body weight and food intake of rats in the model group were significantly decreased， the water intake was significantly increased（P<0.05， P<0.01）， and the duration of swimming was significantly decreased（P<0.01）. Pathological examination results showed that in the mucosa of gastric tissues of rats in the model group appeared to be misaligned， the mucosa of colonic tissues could be seen to be obviously thinned or mutilated， and the epithelial cells appeared to be necrotic or even exfoliated. Compared with the blank group， the urinary D-xylose excretion rate of rats in the model group was significantly decreased（P<0.01）， and the serum GAS content was significantly decreased（P<0.05）. Compared with the blank group， Western blot results showed that the relative expression level of VIP protein in gastric tissues of rats in the model group was significantly decreased， while the relative expression levels of AQP4 and AQP3 proteins were significantly increased（P<0.01）. Compared with the blank group， Real-time PCR results showed that the relative expression level of VIP mRNA in gastric tissues of rats in the model group was significantly decreased（P<0.01）， and the relative mRNA expression levels of AQP3 and AQP4 were significantly increased（P<0.05， P<0.01）. Compared with the blank group， the results of intestinal flora analysis showed that the number of operational taxonomic units（OTUs） and α-diversity increased and β-diversity decreased significantly in the model group， the abundance of Porphyromonadaceae was increased significantly， and the abundance of Oscillibacter_ruminantium was decreased significantly（P<0.05）. Spearman correlation analysis showed that Porphyromonadaceae was significantly positively correlated with AQP4 protein level， while Oscillibacter_ruminantium was significantly positively correlated with VIP protein level， and negatively correlated with AQP3 and AQP4 protein levels（P<0.05）. Linear discriminant analysis effect size（LEfSe） analysis results showed that there were significant differences in a variety of intestinal bacteria between groups， and the intestinal bacteria of the model group were significantly enriched in the phylum/order/family/genus of Elusimicrobia， Betaproteobacteria， Burkholderiales， Sutterellaceae and Parasutterella（P<0.05）. ConclusionSpleen-Yin deficiency syndrome can weaken the digestion and absorption capacity of gastrointestinal tract， and cause the disturbance of water metabolism and intestinal flora. AQP4， AQP3 and VIP protein levels of gastric mucosa are closely related to Porphyromonadaceae and Oscillibacter_ruminantium. And AQP4， AQP3 and VIP may be involved in the regulation of intestinal flora in order to affect the physiological function of spleen governing transportation and transformation.
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ObjectiveTo evaluate the effect of Shengmaisan granules on myocardial fibrosis in chronic heart failure patients with Qi-Yin deficiency syndrome by cardiac magnetic resonance （CMR） imaging and serological indicators. MethodSixty-six chronic heart failure patients with Qi-Yin deficiency syndrome who visited the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine， Nanjing University of Chinese Medicine from October 2021 to January 2023 were selected. The patients were assigned into a control group （33 cases） and an observation group （33 cases） by the minimization random method. Both groups received standardized Western medicine treatment for heart failure. In addition， the control group was treated with placebo granules， and the observation group with Shengmaisan granules for a course of 6 months. The baseline data， clinical efficacy， TCM symptom scores， serological indicators ［high-sensitivity C-reactive protein （hs-CRP）， soluble growth stimulation expressed gene 2 protein （sST2）， pro-collagen Ⅲ N-terminal peptide （PⅢNP）， interleukin （IL）-6， IL-11， transforming growth factor-β1 （TGF-β1）］， echocardiography ［Left atrial diameter （LAD）， left ventricular end systolic diameter （LVEDs）， left ventricular end diastolic diameter （LVEDd）］ and CMR indicators ［left ventricular ejection fraction （LVEF）， myocardial extracellular volume fraction （ECV）， and longitudinal relaxation time （T1）］ were compared between the two groups. ResultFinally， 31 patients in the control group and 30 patients in the observation group were included. There was no significant difference in baseline data or indicators between the two groups before treatment. Compared with those before treatment， the scores of TCM symptoms （shortness of breath， fatigue， palpitations， spontaneous or night sweats， thirst/dry throat， feverish feeling in palms and soles， and edema in lower limbs）， total score of TCM symptoms， ECV， T1， inflammation/fibrosis indicators （hs-CRP， sST2， PⅢNP， IL-6， IL-11， and TGF-β1） in observation group decreased （P<0.05， P<0.01）， and the scores of TCM symptoms （except feverish feeling in palms and soles）， T1， and inflammation/fibrosis indicators in the control group decreased （P<0.05， P<0.01）. After treatment， the observation group had lower scores of TCM symptoms （except feverish feeling in palms and soles and edema in lower limbs）， ECV， T1， and inflammation/fibrosis indicators than the control group （P<0.05， P<0.01）. After treatment， the total response rate in the observation group was 93.33% （28/30）， which was higher than that （80.65%， 25/31） in the control group （Z=2.976， P<0.01）. There was no significant difference in adverse reactions between the two groups during treatment. ConclusionFor patients with chronic heart failure with Qi-Yin deficiency syndrome， Shengmaisan Granules can alleviate the TCM symptoms， reduce inflammation， and inhibit myocardial fibrosis by regulating the TGF-β1/IL-11 signaling axis.
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According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.
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ETHNOPHARMACOLOGICAL RELEVANCE: Insomnia is a common form of sleep disorder. Traditional Chinese medicine (TCM) compounds have definite curative effects and a low incidence of adverse reactions, which is recognized to be an effective intervention means for the treatment of insomnia. AIM OF THE STUDY: Based on mining the clinical research data of treating insomnia of yin deficiency syndrome (IYDS) with TCM compounds systematically, the study is to analyze the research hotspots and development trends in this field, explore the medication rule, evaluate the quality of research, so as to provide reference and direction for clinical application and scientific research in this field. MATERIALS AND METHODS: The relevant literature was retrieved and managed by evidence-based medicine strategy and EndNote software respectively. The bibliometric method was used to mine and analyze data characteristics. The VOSviewer software was used to make visual knowledge maps, the IBM SPSS Modeler software was used for association rule analysis of herbs, and the Cochrane tool and MINORS scale were used for quality analysis of literature. RESULTS: (1) A total of 184 related studies were included according to the inclusion and exclusion criteria. (2) The research popularity showed a dynamic upward trend and the research hotspot showed a trend of migration and refinement, etc. (3) The commonly used herbs in this field were Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F.Chow, etc; the commonly used TCM prescriptions were Huanglian Ejiao Decoction, etc; the commonly used dosage forms were traditional decoction, etc; the commonly used combinations of herbs included Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F.Chow-Poria cocosï¼Schw.ï¼Wolf, etc. (4) The rate of the studies containing ethical review numbers and clear inclusion standards did not reach 50%, and the risk bias of methodological was high. However, a separate analysis of data showed that the specification of study design was on the rise obviously in recent years, and Meta-analysis and sensitivity analysis could confirm the effectiveness and stability of clinical efficacy which was the key indicator in treating IYDS with TCM prescriptions. There were significant differences among administration protocols of different clinical studies of the same name TCM compounds. However, the scientific significance of each unique dosing regimen were expected to be elaborated or discussed. CONCLUSION: The clinical research number of TCM compounds treating IYDS was in a dynamic upward trend, and the outcome indicators tended to be diversified and detailed. The dosage forms mainly included decoction, supplemented by Chinese patent medicine. The design of clinical studies in this field was not standardized enough, but the key indicators were scientific and stable. We expected that later studies could pay more attention to improving the standardization of trial design, reducing the risk bias in the process of methodological design, conducting high-quality standardized multicenter, large-sample randomized controlled clinical trials to provide scientific evidence with high evidentiary strength, establishing the recognized administration protocols for the same name TCM prescriptions or clarifying the targeting of different protocols, and promoting the application and popularity of TCM compounds in treating IYDS.
Subject(s)
Drugs, Chinese Herbal , Sleep Initiation and Maintenance Disorders , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional/methods , Multicenter Studies as Topic , Research Design , Sleep Initiation and Maintenance Disorders/drug therapy , Syndrome , Yin Deficiency/drug therapyABSTRACT
ObjectiveTo explore the structural characteristics and functional differences of intestinal flora in patients with type 2 diabetes mellitus （T2DM） of dampness heat trapping spleen（DHTS） syndrome and Qi-Yin deficiency（QYD） syndrome. MethodFrom June 2018 to January 2020，62 T2DM patients with DHTS syndrome and 60 with QYD syndrome were selected from Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Serum and fecal samples were collected to compare body mass index（BMI），glucose and lipid metabolism，fasting insulin （FINS） and fasting C-peptide （FCP） levels，and homeostasis model assessment of insulin resistance（HOMA-IR） of the two syndrome types. Fecal samples were extracted for DNA database construction，and 16S rDNA high-throughput sequencing was used to analyze and compare the intestinal flora and metabolic pathways. Result① The BMI，fasting plasma glucose（FPG），2-hour postprandial blood glucose （2 h PBG），total cholesterol（TC），triglyceride（TG），low density lipoprotein（LDL），FINS，FCP，and HOMA-IR were higher in patients with DHTS syndrome than in patients with QYD syndrome，and the high density lipoprotein（HDL） of the former was lower than that of the latter，（P<0.05，P<0.01）. ② In terms of species composition and differences，Bacteroidetes， Clostridia and Gammaproteobacteria were dominant at the class level，and the relative abundance of Clostridia，Mollicutes and Verrucomicrobiae in QYD syndrome group was higher than that in DHTS syndrome group. At the order level，Bacteroidales，Clostridiales and Enterobacteriales were mainly found. The relative abundance of Clostridiales，Erysipelotrichales and Verrucomicrobiales in QYD syndrome group was obviously higher than that in DHTS syndrome group，while Aeromonadales in the former was lower than that in the latter （P<0.05）. At the family level，Bacteroidaceae，Prevotellaceae and Ruminococcaceae were predominant. The relative abundance of Ruminococcaceae，Porphyromonadaceae and Erysipelotrichaceae in QYD syndrome group was higher than that in DHTS syndrome group（P<0.05）. At the genus level，Bacteroides，Prevotella and Parabacteroides were mainly found. The relative abundance of Parabacteroides，Butyrivibrio and Ruminiclostridium in QYD syndrome group was higher than that in DHTS syndrome group，while that of Klebsiella and Megasphaera in DHTS syndrome group was higher than that in QYD syndrome group（P<0.05）. ③ Through Venn analysis of operational taxonomic units（OTU），it was found that there were 49 OTUs in patients with DHTS syndrome patients and 47 OTUs in QYD syndrome patients. ④ The results of OTU β diversity and α analysis showed that Shannon and Simpson indexes had statistical differences，while Ace and Chao indexes had no statistical differences. The intestinal microbial diversity of patients with QYD syndrome was higher than that of patients with DHTS syndrome（P<0.05）. The analysis of similarities （ANOSIM） showed that the difference of β diversity between the two groups was significant（P<0.05）. ⑤ Linear discriminant analysis Effect Size（LEfSe） results demonstrated that Klebsiella，Megasphaera and Aeromonadales could be selected as the key biomarkers for DHTS syndrome； 14 bacteria such as Ruminiclostridium，Burkholderiaceae，Lautropia，Butyrivibrio，Erysipelotrichales can be selected as the key biomarkers for QYD syndrome. ⑥Functional annotation and analysis showed that the DHTS syndrome involved 9 metabolic pathways，including arginine and proline metabolism，lipopolysaccharide biosynthesis，nicotinic acid and nicotinamide metabolism，while the QYD syndrome involved 10 metabolic pathways，including acarbose and valinomycin biosynthesis，glucagon signaling pathway and NOD-like receptor signaling pathway. ConclusionThere are obvious differences in intestinal flora and functions in T2DM patients of DHTS syndrome and QYD syndrome，which can be used as reference for traditional Chinese medicine （TCM） syndrome differentiation and the target of TCM treatment.
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Objective:To observe the effects of modified Huangqi Biejiatang combined with auricular acupressure on diabetic peripheral neuropathy （DPN） due to Qi and Yin deficiency and serum myeloid differentiation factor 88/inhibitor of nuclear factor-<italic>κ</italic>B （MyD88/I<italic>κ</italic>B） signaling pathway. Method:One hundred and forty cases were randomly divided into an observation group （<italic>n</italic>=70） and a control group （<italic>n</italic>=70）. In addition to routine treatments like dietary intervention and the regulation of fasting blood glucose （FBG） and blood pressure， the modified Huangqi Biejiatang combined with auricular acupressure was further provided in the observation group， while mecobalamine was administered in the control group. After four-week intervention， the toronto clinical scoring system （TCSS） score， traditional Chinese medicine （TCM） syndrome score， the conduction velocities of motor and sensory nerves （median nerve， common peroneal nerve， tibial nerve， and ulnar nerve）， glucose metabolism indexes ［fasting plasma glucose （FPG）， 2 h postprandial blood glucose （2 h PG）， and hemoglobin A1c （HbA1c）］， intestinal genera （<italic>Clostridium</italic>， <italic>Prauserella</italic>， <italic>Bacteroides</italic>， and <italic>Faecalibacterium</italic>）， as well as the serum MyD88， I<italic>κ</italic>B<italic>α</italic>， and phosphorylated I<italic>κ</italic>B<italic>α </italic>（p-I<italic>κ</italic>B<italic>α</italic>） levels in the MyD88/I<italic>κ</italic>B signaling pathway before and after treatment were observed in the two groups， for comparing their clinical efficacy and safety. Result:The total effective rate of the observation group was 85.3% （58/68）， which was higher than 48.5% （32/66） of the control group （<italic>χ</italic><sup>2</sup>=6.143， <italic>P</italic><0.05）. The comparison with the control group revealed that the scores of TCSS and TCM syndrome， the levels of FPG， 2 h PG， HbA1c， MyD88， and p-I<italic>κ</italic>B<italic>α</italic>， as well as the abundances of <italic>Clostridium</italic> and <italic>Prauserella</italic> in the observation group were decreased （<italic>P</italic><0.05）， while the conduction velocities of motor and sensory nerves （median nerve， common peroneal nerve， tibial nerve， and ulnar nerve） were significantly accelerated （<italic>P</italic><0.05）. Besides， the abundances of <italic>Bacteroides</italic> and <italic>Faecalibacterium</italic> and I<italic>κ</italic>B<italic>α</italic> level were significantly elevated （<italic>P</italic><0.05）. The incidence of adverse reactions in the observation group was 1.5% （1/68）， lower than 12.1% （8/66） in the control group （<italic>χ</italic><sup>2</sup>=4.328， <italic>P</italic><0.05）. Conclusion:The modified Huangqi Biejiatang combined with auricular acupressure alleviates DPN due to Qi and Yin deficiency， which may be attributed to the regulation of serum MyD88/I<italic>κ</italic>B signaling pathway.
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Objective:To explore the clinical efficacy of modified Zhizhutang in treating senile primary constipation due to Qi-Yin deficiency and its influences on gastrointestinal neurotransmitters and gastrointestinal motility. Method:One hundred and twenty-one eligible patients were randomly divided into a control group （<italic>n</italic>=60） and an observation group （<italic>n</italic>=61）. On the basis of lifestyle adjustments， patients in the control group further received oral Qihuang Tongmi soft capsule，three capsules per time，three times per day， whereas those in the observation group were further treated with modified Zhizhutang，one bag per day， for eight successive weeks. The number of complete spontaneous bowel movements （CSBM， normal defecation was considered if CSBM ≥ three times per week） before and after treatment was recorded. The main symptoms of constipation，the patient assessment of constipation quality of life （PAC-QOL）， and the traditional Chinese medicine （TCM） syndrome before and after treatment were scored， followed by the anorectal pressure measurement and colonic transit test before and after treatment. The levels of somatostatin （SS），motilin （MTL），substance P （SP） and vasoactive intestinal peptide （VIP） before and after treatment were detected. Result:The weekly average number of CSBM in the observation group was greater than that of the control group （<italic>P</italic><0.01）， but the TCM syndrome score was lower than that of the control group （<italic>P</italic><0.01）. The normal defecation rate in the observation group was 57.38% （35/61），which was higher than 35% （21/60） of the control group （<italic>χ</italic><sup>2</sup>=6.092，<italic>P</italic><0.05）. The scores of the main symptoms of constipation in the observation group were significantly lower than those in the control group （<italic>P</italic><0.01）. The PAC-QOL subscale scores and the total score of the observation group significantly declined as compared with those of the control group （<italic>P</italic><0.01）. The anal resting pressure and anal maximum systolic pressure of the observation group were higher than those of the control group （<italic>P</italic><0.01），while the first sensation volume， urge sensation volume and maximum tolerable volume were lower （<italic>P</italic><0.01）. The excretion rates of markers in the observation group at 24 h，48 h and 72 h were significantly elevated in comparison with those in the control group （<italic>P</italic><0.01）. Compared with the control group， the observation group also exhibited increased serum MTL and SP （<italic>P</italic><0.01） and decreased SS and VIP （<italic>P</italic><0.01）. The recurrence rate in the observation group was 34.29% （12/35），obviously lower than 61.90% （13/21） in the control group （<italic>χ</italic><sup>2</sup>=5.051，<italic>P</italic><0.05）. The total effective rates in the observation group and the control group were 95.08% （58/61） and 81.67% （49/60） ， implying a significant difference （<italic>χ</italic><sup>2</sup>=5.321，<italic>P</italic><0.01）. Conclusion:For the elderly with primary constipation due to Qi-Yin deficiency， oral administration of modified Zhizhutang helps to regulate gastrointestinal neurotransmitters，improve gastrointestinal motility and gastrointestinal emptying rate， alleviate the symptoms of constipation， restore spontaneous bowel movements， improve their quality of life， and lower the recurrence rate. Its clinical effects were better than those of Qihuang Tongmi soft capsule.
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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.
Subject(s)
Biomarkers/blood , Medicine, Chinese Traditional , Metabolomics , Yin Deficiency/diagnosis , Animals , Chromatography, Liquid , Female , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry , Yin Deficiency/bloodABSTRACT
ShenqiJiangtang Granule is composed of Panax ginseng, Astragali Radix and other valuable Chinese herbal medicines and extract, which has the effect of replenishing qi and nourishing yin, nourishing spleen and kidney, and it is also widely used in the treatment of type 2 diabetes and complications. After more than 20 years of clinical application, abundant research data have been accumulated. In order to accurately locate the clinical position and promote the rational use of drugs, a project was established by the Chinese Society of Traditional Chinese Medicine and experts organized by the Diabetes Branch to compile this consensus. This consensus defines the application of ShenqiJiangtang Granule in the clinical treatment of prediabetes, type 2 diabetes and its complications. It is suitable for clinicians at all levels of hospitals and grass-roots medical and health institutions across the country (traditional Chinese medicine, Western medicine, integrated traditional Chinese and Western medicine).
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ETHNOPHARMACOLOGICAL RELEVANCE: Er-Zhi-Wan (EZW), a famous traditional Chinese formulation, is used to prevent, or to treat, various liver and kidney diseases for its actions of replenishing liver and kidney. However, the mechanisms of treating Liver-kidney Yin deficiency syndrome (LKYDS) of EZW have not been comprehensively investigated. AIM OF THE STUDY: In this study, a broad range metabolomics strategy coupled with network analysis was established to investigate possible mechanisms of EZW in treating LKYDS. MATERIALS AND METHOD: The rat models of LKYDS were established using the mixture of thyroxine and reserpine, and the changes of biochemical indices in serum and histopathology were detected to explore the effects of EZW. Next, a broad range metabolomics strategy based on RPLC-Q-TOF/MS and HILIC-Q-TOF/MS has been developed to find the possible significant metabolites in the serum and urine of LKYDS rats. Then, network analysis was applied to visualize the relationships between identified serum and urine metabolites and in detail to find hub metabolites, which might be responsible for the effect of EZW on rats of LKYDS. Furthermore, the shortest path of "disease gene-pathway protein-metabolite" was built to investigate the possible intervention path of EZW from the systematic perspective. RESULTS: Five hub metabolites, namely, arachidonic acid, L-arginine, testosterone, taurine and oxoglutaric acid, were screened out and could be adjusted to recover by EZW. After that, the shortest path starting from disease genes and ending in metabolites were identified and disclosed, and the genes of aging such as CAV1 and ACO1 were selected to explain the pathological mechanism of LKYDS. CONCLUSION: Broad range metabolomics coupled with network analysis could provide another perspective on systematically investigating the molecular mechanism of EZW in treating LKYDS at metabolomics level. In addition, EZW might prevent the pathological process of LKYDS through regulating the disturbed metabolic pathway and the aging genes such as CAV1 and ACO1, which may be potential targets for EZW in the treatment of LKYDS.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Kidney/drug effects , Liver/drug effects , Yin Deficiency/drug therapy , Aging/genetics , Animals , Disease Models, Animal , Kidney/metabolism , Kidney/pathology , Liver/metabolism , Liver/pathology , Male , Mass Spectrometry , Medicine, Chinese Traditional/methods , Metabolomics/methods , Rats , Rats, Sprague-Dawley , Syndrome , Yin Deficiency/metabolismABSTRACT
Objective:To observe the effect of addition and subtraction therapy of Guyinjian on oocyte quality, pregnancy outcome and ovarian reserve function in patients with poor ovarian response (POR) with kidney Yin deficiency syndrome. Method:Ninety patients were randomly divided into control group (45 cases) and observation group (45 cases) by random number table. The patients in both groups got antagonist. Based on such treatment, the patients in observation received additional addition and subtraction therapy of Guyinjian. The using time and amount of gonadotropin (Gn), ovum taking cycle, cycle canceling rate, fertilization rate, available embryo rate, quality embryo rate, ovulation cycle clinical pregnancy rate were recorded. Levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), serum estradiol (E2) and endometrial thickness, anti mullerian hormone (AMH), resistance index (RI), pulsation index (PI), end diastolic velocity (EDV) and peak systolic velocity (PSV) were detected. Ratio of PSV/EDV (S/D) was calculated, and scores of kidney yin deficiency syndrome were graded before and after treatment. Result:Total amount of Gn in observation group was less than that in control group (PP2 were higher than those in control group (PPPχ2=5.124, Pχ2=5.767, PPPPPConclusion:Addition and subtraction therapy of Guyinjian can increase ovarian blood supply, improve high ovarian reserve function, reduce Gn consumption, increase number of acquired eggs, alleviate symptoms of kidney yin deficiency, and can ameliorate ovarian responsiveness and pregnancy outcome.
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Objective: To explore the laws of core symptom and traditional Chinese medicine(TCM) prescription in treatment of the Yin deficiency syndrome of systemic lupus erythematosus (SLE), in order to provide the objective basis for the treatment of SLE with TCM based on complex network. Method: Complex network analysis method was used to retrospectively study 322 TCM prescriptions collected from the First Affiliated Hospital of Guangzhou University of Chinese Medicine between January 2011 and May 2017 and 134 literatures about treatment of SLE with TCM through computer retrieval. The topological property parameters of the complex network were calculated, and used to analyze the structure of the core network and the compatibility rule of symptom and TCM. Then the core syndrome, herbs, compatibility rules and characteristics of commonly used prescriptions for SLE were analyzed. Result: The results of analysis of complex network showed that the core TCM herbs for Yin deficiency syndrome of SLE mainly included Rehmanniae Radix, Moutan Cortex, Paeoniae Radix Rubra, Anemarrhenae Rhizoma, Scutellariae Radix, Artemisiae Annuae Herba, Cornt Fructus, Gentianae Macrophyllae Radix, Trionycis Carapax, Ligustri Lucidi Fructus, Paeoniae Radix Alba, Poria, Alismatis Rhizoma, Coicis Semen, Dioscoreae Rhizoma, Glycyrrhizae Radix et Rhizoma, Pinelliae Rhizoma.Core prescriptions included Qinghao Biejia Tang and Liuwei Dihuang Wan. Core syndromes included fatigue, poor sleep, anorexia, low fever, five upset heat, night sweats, dizziness, rash, skin erythema, facial red butterfly erythema, dark red rash, alopecia, weak waist and knees, joint pain, muscle pain, tinnitus, thirst, sore throat, red tongue, tongue with less fur, and thready and rapid pulse. Compared with the diagnostic criteria of the syndrome, the core symptoms included some new common clinical symptoms, such as poor sleep, anorexia, facial red butterfly erythema, dark red rash. Conclusion: The main pathogenesis of SLE is Yin deficiency and blood heat, so the treatment should be nourishing Yin and generating body fluid, removing pathogenic heat from blood and clearing deficient heat. In this study, the results of clinical retrospective review and computer retrieval by the complex network analysis method were basically consistent with the clinical application. It can be used as a reference for the clinical syndrome differentiation and treatment of Yin deficiency syndrome of SLE.
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Objective:To observe the clinical efficacy of addition and subtraction therapy of Liuwei Dihuangwan combined with Huanglian Ejiaotang to primary insomnia in the elderly (liver and kidney Yin deficiency syndrome), and to investigate its regulation effect on neurotransmitter. Method:Randomly 136 patients were divided into control group (68 cases) and observation group (68 cases) by number table. Patients in control group got Estazolam tablets by oral administration before going to bed, 1-2 mg/time, 1 time/day. Patients in observation group got addition and subtraction therapy of Liuwei Dihuangwan combined with Huanglian Ejiao tang, 1 dose/day. Both groups of patients received sleep guidance and cognitive behavior guidance, with treatment course of 8 weeks. During the observation period, physical therapy and acupuncture could not been used. Before and after treatment, pittsburgh sleep quality index (PSQI), whole night polysomnography, sleep latency (SL), awakening times (AT), sleep efficiency (SE), rapid eye movement (REM), latency (RL), total actual sleep time (TST) and proportion of N1, N2, N3 and REM in the whole sleep stage were recorded. Scores of self-rating depression scale (SDS), self-rating anxiety scale (SAS), kidney Yin deficiency syndrome score and treatment emergent symptom scale (TESS) were graded, and levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid(5-HIAA), gamma-aminobutyric acid (GABA), norepinephrine (NE) and dopamine (DA) were detected. Result:In rank sum test, clinical efficacy in observation group was better than that in control group (Z=2.115, PPPPPPPPχ2=9.945, PConclusion:Addition and subtraction therapy of Liuwei Dihuangwan combined with Huanglian Ejiaotang can improve sleep quality, prolong sleep time, alleviate depression, anxiety, and can also regulate neurotransmitters to improve sleep effect. The efficacy of PSQI is better than that of Estazolam tablets.
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[Objective] To systematically study the characteristics of the key syndromes of systemic lupus erythematosus(SLE),summarize its clinical efficacy,and explore the mechanism of traditional Chinese medicine(TCM).[Methods] The main clinical syndrome features of SLE are heat-toxicity,blood stasis and Yin-deficiency.Compared with glucocorticoids(GCs) alone,combination with JP can significantly improve the clinical efficacy and reduce the glucocorticoid treat consumption effectively.[Results]Our results showed that in MRL/LPR model mice,JP could restore the balance between TH17 and regulatory T cells through CaMK4 signaling pathway,and the interaction between T cells and B cells.JP could promote DNA methylation,inhibit the over-activated lymphocytes,improve the prognosis of SLE and prevent renal damage.JP could up-regulate the concentration of eicosapentaenoic acid (EPA) and the level of glycine,phenylalanine and tryptophan dramatically.Furthermore,JP could reduce the abundance of pathogenic bacteria(such as Parabacteroides) and increase the abundance of beneficial bacteria (such as Odoribacter and Ruminococcus) by regulating gastrointestinal function,which was not found in GCs treated subjects.JP can also obviously reduce the expression of TLR7,TLR9 and IL-6 in intestinal mucosa,showing the effect of multi-target therapy on SLE.[Conclusion] The most common clinical syndromes of SLE are heat-toxicity,blood stasis and Yin-deficiency.JP can effectively control the progress of SLE and exert its clinical function from different aspects.Our research laid the scientific basis for the popularization and application of TCM in clinical treatment of SLE.
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AIM To investigate the clinical effects of Qingrun Yangmu Oral Liquid combined with artificial tears on dry eye visual fatigue patients due to Liver-Kidney Yin Deficiency Syndrome.METHODS Ninety patients (180 eyes) randomly and equally were divided into artificial tears group (0.1％ Sodium Hyaluronate Eye Drops),oral liquid group (Qingrun Yangmu Oral Liquid) and combination group (0.1％ Sodium Hyaluronate Eye Drops and Qingrun Yangmu Oral Liquid) underwent a ten-day course of treatment,and they had their subjective symptom score,tear secretory volume (Schirmer Ⅰ test,SIT),tear film break-up time (BUT),corneal fluorescein staining (CFS) score and visuognosis persistence observed prior to the treatment,and on the 1 lth,21st,30th days after the treatment.RESULTS All the aforementioned indices in the three groups were improved after the treatment,especially of the 11th day (P ＜0.01).Obvious changes of BUT,CFS score and visuognosis persistence at different time points,in the three groups were found as compared with those data prior to the treatment (P ＜0.05),so were the subjective symptom score and SIT in the oral liquid group and combination group (P ＜ 0.05).The combination group displayed significantly better results than the other two groups (P ＜ 0.05),which exhibited no obvious differences between the interventions of artificial tears and oral liquid (P ＞ 0.05).A markedly higher total efficacy rate of combination group than the other two groups was achieved as well (P ＜ 0.05).CONCLUSION For patients of dry eye visual fatigue due to Liver-Kidney Yin Deficiency Syndrome,Qingrun Yangmu Oral Liquid combined with artificial tears can relieve their symptoms in terms of tear secretory promotion and prolonged BUT.
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Angelicae Sinensis Radix, with nourishing Yin, promoting blood circulation, and moisturizing dryness functions, is commonly used in clinical medicine. In order to investigate the effects and mechanism of Angelica sinensis(AS) on Th1/Th2 and Th17/Treg in mice with asthma and Yin deficiency syndrome, asthmatic and Yin deficiency syndrome Balb/c mice models were established by injecting and inhaling ovalbumin(OVA) and thyroxin. The models were treated with dexamethasone(DXM), AS extract and AS extract+DXM, respectively. Pathological examination of lung tissues was conducted by HE staining, and ELISA was used to detect the levels of IL-4, IL-17, IFN-γ, TGF-ß as well as retinoic acid receptor-related orphan receptor (RORγt). Results showed that AS could significantly improve the situation of inflammation infiltration, increase ratios of IFN-γ/IL-4 and TGF-ß/IL-17, decrease the levels of RORγt in lung tissues. The AS+DXM group showed a best treatment effect. The results indicated that AS played a therapeutic role for asthma with Yin deficiency syndrome and improved airway inflammation by inhibiting the expression of RORγt in lung tissues and regulating the balance of Th1/Th2 and Th17/Treg.
Subject(s)
Angelica sinensis/chemistry , Asthma/drug therapy , Drugs, Chinese Herbal/pharmacology , T-Lymphocytes, Helper-Inducer/drug effects , T-Lymphocytes, Regulatory/drug effects , Yin Deficiency/drug therapy , Animals , Cytokines/metabolism , Disease Models, Animal , Lung/drug effects , Lung/metabolism , Mice , Mice, Inbred BALB C , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Ovalbumin , T-Lymphocytes, Helper-Inducer/cytology , T-Lymphocytes, Regulatory/cytology , Th17 Cells/cytology , Th17 Cells/drug effectsABSTRACT
Coronary heart disease (CHD) is a disease with high incidence which is threat to human health. CHD belongs to the chest pain, palpitations, etc in traditional Chinese medicine (TCM). Nowadays the research on TCM syndrome type of coronary artery disease animal model gradually becomes hot topics in the study of traditional Chinese medicine. Through the comprehensive retrieval and analysis of the related literatures of TCM syndromes of CHD, it is found that qi and yin deficiency syndrome is the main type of syndrome of CHD. This article takes CHD qi and yin deficiency syndrome as the research object, through the strict inclusion and exclusion criteria and retrieval system, all the literatures related to clinical trials of CHD qi and yin deficiency syndrome were collected. Through the analysis on literatures of clinical evaluation, the evaluation indexes of CHD qi and yin deficiency syndrome animal model are explored, and aims to build evaluation standard for CHD qi and yin deficiency syndrome animal model.
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Objective To seek for the differentially-expressed proteins in patients with kidney-yin deficiency syndrome and to screen out the specific proteins,so as to provide evidence for the establishment of objective standard of kidney deficiency syndrome of traditional Chinese medicine (TCM).Methods Five patients with typical kidney-yin deficiency syndrome and 6 normal healthy volunteers were enrolled into the study.Plasma proteins in both groups were detected by antibody chip,and then the plasma proteins profile was compared and analyzed.Results A total of 25 differentially-expressed proteins between kidney-yin deficiency group and normal control group were found,of which 2 were up-regulated and 23 were down-regulated.Conclusion The differentially-expressed proteins in patients with kidney-yin deficiency syndrome are mainly related to immune disorder,protein biosynthesis,metabolism,oxidative stress,cell apoptosis,signal transduction,and so on.
