A real-world data analysis-based study of Chinese medicine treatment patterns after breast cancer surgery.

Based on the real clinical data of Hospital Information System to explore the common clinical syndromes of traditional Chinese medicine after breast cancer surgery, analysis of traditional Chinese medicine in the treatment of breast cancer after the compatibility law. The real medical records of breast cancer patients after surgery in a tertiary hospital in Sichuan Province were collected and screened to build a medical record database. Python language was used for data preprocessing to remove outliers and fill in missing values. Using International Business Machines Corporation (IBM) Statistical Product and Service Solutions (SPSS) Modeler software, Apriori association rules algorithm for data analysis, mining Chinese medicine treatment of breast cancer after common syndromes and the corresponding medication rules. A total of 472 cases of clinical real medical record data were included. Data analysis showed that there were 42 TCM syndromes after breast cancer surgery, of which the highest frequency was liver depression and spleen deficiency, qi deficiency and blood stasis, qi stagnation and blood stasis, qi and blood deficiency, qi and yin deficiency, phlegm and blood stasis. A total of 416 kinds of traditional Chinese medicine were involved. High-frequency drugs included angelica sinensis, coix seed, bupleurum, ginger magnolia bark, keel, oyster, astragalus, platycodon grandiflorum, antler frost, vinegar tortoise shell, poria cocos, lily, Jianqu, Ophiopogon japonicus (Maidong), Shancigu, etc. A total of 18 pairs of commonly used drug combinations were excavated, such as Fushen-Gancao-Chaihu-Angelica, Huangqi-Baishao-Jianghoupu, Chaihu-Huanhua-Maidong-Lily, Baizhu-Huangqi-Maidong, Fuling-Baishao, etc. The clinical syndrome type of traditional Chinese medicine after breast cancer surgery is mainly liver depression and spleen deficiency syndrome. The clinical treatment is mainly soothing liver and relieving depression, and harmonizing liver and spleen. Analyze the syndrome type and the corresponding drug compatibility law, and provide decision support for the clinical dialectical prescription of traditional Chinese medicine after breast cancer surgery.

[Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics].

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).

[Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway].

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

Comparing steamed and wine-stewed Rehmanniae Radix in terms of Yin-nourishing effects via metabolomics and microbiome analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmanniae Radix Praeparata (RRP), the processed root of Rehmannia glutinosa, has been widely used to treat Yin deficiency syndrome in traditional Chinese medicine. RRP is available in two forms: processed by steaming with water (SRR) or processed by stewing with yellow rice wine (WRR). Previous work has documented chemical differences in the secondary metabolomes and glycomes of SRR and WRR. AIM OF THE STUDY: This study aimed to compare SRR and WRR in terms of Yin-nourishing effects via metabolomics and microbiome analysis. MATERIALS AND METHODS: ICR mice were orally administered with thyroxine for 14 d to induce Yin deficiency. Changes in biochemical indices and histopathology were detected. Serum metabolomics analysis and microbial 16S rRNA sequencing were performed to compare the therapeutic effects and mechanisms between SRR and WRR in treating thyroxine-induced Yin deficiency. RESULTS: Both SRR and WRR decreased serum T3, T4 and MDA levels, and increased SOD activity. SRR more effectively decreased serum Cr, and ameliorated kidney injury, while WRR showed better regulation on ratio of cAMP/cGMP and serum TSH, and relieved thyroid injury. Both SRR and WRR regulated tyrosine, glycerophospholipid, and linoleic acid metabolism and the citric acid cycle. Additionally, SRR regulated fatty acid metabolism, while WRR influenced alanine, aspartate and glutamate metabolism, and bile acid biosynthesis. SRR significantly enriched the genera Staphylococcus and Bifidobacterium in the gut microbiome, while WRR significantly enriched the genera Akkermansia, Bacteroides and Parabacteroides, and decreased the abundance of Lactobacillus. CONCLUSIONS: SRR displayed better protective effects on kidney, while WRR showed stronger effects on thyroid in thyroxine-induced Yin deficient mice. These differences might be due to different regulating effects of SRR and WRR on the metabolome and gut microbiota.

Twelve-component pharmacokinetic study of rat plasma after oral administration of You-Gui-Wan in osteoporosis rats with kidney-yin deficiency and kidney-yang deficiency.

You-Gui-Wan is a widely used traditional Chinese medicine preparation for the treatment of osteoporosis with kidney-yang deficiency, and is composed of both yang-invigorating and kidney-tonifying herbs, and yin-nourishing and kidney essence-replenishing herbs. Considering that the pharmacokinetics of drugs might differ in different pathological conditions, it is necessary to study the pharmacokinetic characteristics of You-Gui-Wan under different osteoporotic conditions. In this study, the pharmacokinetic behaviors of You-Gui-Wan in osteoporosis rats with kidney-yin and kidney-yang deficiency were compared. The results showed that the absorption, metabolism, and disposition of You-Gui-Wan varied widely in animals with different types of osteoporosis. The active components belonging to the yang-invigorating herbs, such as aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypacoitine, benzoylmesaconine, chlorogenic acid and pinoresinol diglucoside, had a higher uptake and slower elimination in osteoporosis rats with kidney-yang deficiency, which corresponds to the opinion that You-Gui-Wan is used to treat kidney-yang deficiency syndrome, and indicates the scientific nature of Bian-Zheng-Lun-Zhi.

Synergistic effect of constituent drugs of Baibutang on improving Yin-deficiency pulmonary fibrosis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Baibutang (BBT) is an ancient prescription for the treatment of pulmonary fibrosis. Previous experiments have shown that BBT had a good therapeutic effect on pulmonary fibrosis. However, there had been no study on the synergy between drugs composed of BBT. Due to the interaction between the constituent drugs, exploring their synergy profile is of great significance for explaining the essence of BBT's efficacy in improving pulmonary fibrosis. AIM OF THE STUDY: Based on the pharmacodynamic value, this study aimed to explore a method for the evaluation of the synergy profile between constituent drugs in traditional Chinese medicine (TCM) compounds. MATERIALS AND METHODS: Nine herbs of BBT were divided into Zhikeqingre (ZK), Yangyinyiqi (YY) and Lishijianpi (LS) groups. A rat model of Yin-deficiency pulmonary fibrosis induced by thyroxine-bleomycin was used to evaluate the effects of BBT and the three groups. The pathological changes of lung tissue and the changes of biomarkers associated with fibrosis, Yin-deficiency and water-fluid metabolism were detected. After standardization of pharmacodynamics value (PV), the compatibility coefficient (CC) of the three groups, the relative PV (RPV) and contribution value (CV) of each group on every index were calculated. RESULTS: The average CC on fibrosis indexes was 0.44, indicating that 44% of the efficacy of BBT came from the synergistic effect of the three groups. ZK group had the highest RPV (0.80) in improving fibrosis indexes such as histopathological changes, α-SMA, collagen-I and renin-angiotensin system. The average CC on Yin-deficiency indexes was 0.25, and YY group had the highest RPV (0.96) in improving deficiency indexes such as body temperature, cAMP/cGMP ratio, and PDEs, PGE2 and COX-2 levels. The average CC on water-fluid metabolism indexes was 0.15, and LS group had the highest RPV (1.52) in improving water-fluid metabolism indexes such as aquaporins, mucins, and surfactant proteins. The results also showed that 29% of the improvement effect of BBT on all indexes came from the synergistic effect of the three groups, and the contribution of ZK, YY and LS groups to the efficacy of BBT were 25%, 25% and 21%, respectively. CONCLUSION: The established semiquantitative method can clearly and simply evaluate the synergy of the three groups in BBT, which will help to promote the research on the synergy of TCM compounds and other multiple-components combinations.

Visual analysis and evaluation of clinical research on Traditional Chinese medicine compounds in treating insomnia of Yin deficiency syndrome.

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 cocos（Schw.）Wolf, 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.

[Priority ranking of Chinese patent medicine prescriptions for type 2 diabetes mellitus (syndrome of deficiency of both Qi and Yin): based on analytic hierarchy process (AHP)].

Clinical expertise, patient preference, and the best evidence are the three elements of evidence-based medicine. Based on high-level and high-quality evidence, qualitative and quantitative analysis of the prescribing decisions of physicians is beneficial to improving clinical efficacy. A mature methodological system is available for the retrieval, analysis, summary, evaluation, and recommendation of the evidence, but there are still few studies on physicians' prescribing decisions. How to analyze the trend of physicians' prescribing decisions based on the priority ranking in addition and subtraction of prescriptions? Analytic hierarchy process(AHP) is a method for decision making, which arranges the elements of the decision problem into overall goal, criteria, and operational sub-criteria, and uses the matrix eigenvector method to solve the problem. This study aims to analyze the priority of physicians' prescribing decisions for diabetes mellitus with deficiency of both Qi and Yin based on AHP. To be specific, a database of diabetes mellitus cases with deficiency of both Qi and Yin was established and AHP was used to yield the priority ranking of Chinese patent medicine prescriptions in specific clinical scenarios. In the selected cases of diabetes mellitus with deficiency of both Qi and Yin, Xiaoke Pills was the best prescription for the treatment of type 2 diabetes mellitus(deficiency of both Qi and Yin)(normalized=0.388), followed by Liuwei Dihuang Pills(normalized=0.269), Qishen Capsules(normalized=0.230), and Shengmai Injection(normalized=0.113). According to the analysis the available data, for type 2 diabetes mellitus(deficiency of both Qi and Yin), Xiaoke Pills was the most effective prescription in specific scenarios. When the physicians' prescribing decisions are consistent with the evidence, quantitative analysis of physicians' cognition will boost the evidence-based medical decision-making. However, the research results are also affected by the quality of literature, evidence level and priority, which are thus have some limitations. It is recommended that further small data research based on individual cases be carried out to lay a evidence-based basis for the clinical decision-making of type 2 diabetes mellitus.

[Pharmacoeconomic evaluation of Qidong Yixin Oral Liquid in treatment of viral myocarditis (Qi-Yin deficiency syndrome) with TreeAge Pro].

To evaluate the pharmacoeconomic value of Qidong Yixin Oral Liquid in the treatment of viral myocarditis(Qi-Yin deficiency syndrome) by supplementing Qi, nourishing the heart, calming the mind, and relieving palpitation, the present study performed the Meta-analysis based on the published papers on Qidong Yixin Oral Liquid by AMSTAR and carried out pharmacoeconomic evaluation using TreeAge Pro by the cost-effectiveness analysis. The results showed that the quality of the included papers was good. After four weeks of treatment, Qidong Yixin Oral Liquid combined with the conventional treatment regimen was superior to the conventional treatment in improving creatine kinase isoenzyme, and the difference was statistically significant. Furthermore, the treatment cost was also higher than that of conventional treatment, with an incremental cost-effectiveness ratio of CNY 95.89, accounting for 0.30% of per capita disposable income. The results of sensitivity analysis showed that the research results were robust. Therefore, based on the assumption that the per capita disposable income in 2020 was the threshold of patients' willingness to pay, it is more economical for patients with viral myocarditis to use Qidong Yixin Oral Liquid combined with conventional secondary prevention regimen than conventio-nal secondary prevention regimen alone. The economic evaluation of Qidong Yixin Oral Liquid in the treatment of viral myocarditis will help physicians and patients choose optimal treatment options, improve rational clinical medication, and provide references for the efficient allocation and utilization of medical resources in China.

[Effects of Angelicae Sinensis Radix on cAMP/Epac signaling pathway in the treatment of chronically infected cough mice with Yin deficiency syndrome].

OBJECTIVE: To investigate the effects of Angelicae Sinensis Radix (ASR) on cyclic adenosine monophosphate (cAMP) /exchange protein activated by cAMP (Epac) signaling pathway in the treatment of chronically infected cough mice with Yin deficiency syndrome. METHODS: Mice were randomly divided into blank control group, model control group, positive control group and ASR group (n=8). The chronic cough mouse model of hyperreactive and infected airway with Yin deficiency syndrome was established with fumigation (once a day, 30 days in total), lipopolysaccharide nasal drip (every 3 days 10 µl, 10 times in total), intragastric administration of thyroid gland (120 mg/kg, once a day, a total of 15 days) and inhalation of ammonia (3 min / time × 10 times). On the basis of observing eating and drinking water, body weight and autonomic activities, the effects of ASR on metabolic level, autonomous activities, antitussive effect, cell factor in bronchoalveolar lavage fluid (BALF) brain tissue 5-HT and lung tissue related active factors(SP, PGP9.5, cAMP, Epac1) were detected. RESULTS: ASR could significantly restrain cough, alleviate the pathological changes of bronchioles, reduce the contents of IL-4, IL-13, TNF-α in BALF and the levels of SP, PGP9.5, cAMP and Epac1 in lung tissues, increase the content of 5-HT in brain tissue (P＜0.05, 0.01). CONCLUSION: ASR has some effects on restraining cough and one of its mechanisms is to down-regulate cAMP/Epac signaling pathway, to alleviate airway neurogenic inflammation and reduce sensitivity of cough neural pathway.

Zuogui Wan alleviated maternal kidney-yin deficiency-induced thymic epithelial cell dysfunction in newborn rats through Wnt/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Kidney-yin deficiency (KYD) during pregnancy is common and associated with possibility of thymus hypoplasia in neonates. Zuogui Wan (ZGW) is a classic traditional medicine to treat KYD. AIM OF STUDY: The Wnt/ß-catenin signaling pathway is essential for thymic epithelial cell (TEC) viability, function and for thymus integrity. We evaluated whether maternal diets with ZGW in KYD rats ameliorates epithelial cell dysfunction in the fetal thymus, and investigated its underlying mechanism in which the Wnt/ß-catenin signaling pathway is involved. MATERIALS AND METHODS: Rats were randomly assigned to four groups (n = 8). Two experimental groups received KYD induction with or without ZGW supplementation. The other 2 vehicle groups were sham operated and administrated with normal saline or ZGW. KYD was established using periodically chronic shaken stimulus and threaten stress. Success of the model induction was evaluated by the general observation, changing of the body weight and plasma thyroxine level. Then, pregnant of vehicle and KYD rats were fed with or without ZGW-supplemented diet throughout the F1 gestation. Postnatal thymi samples were obtained after delivery for histological examination. In vitro, TECs of the newborn rats whose mother suffered KYD were isolated, and cultured using the serum containing ZGW with or without the supplement of Wnt4/ß-catenin pathway inhibitor ICG-001. Cell viability was evaluated by CCK-8 assay. Meanwhile, the thymi tissues and TECs were collected for biochemical analysis. Levels of thymosin ß4 (TMSß4) and thymosin α1 (Tα1) were detected by ELISA assay. The mRNA and protein expression of Wnt4, ß-catenin, and Foxn1 were determined by RT-qPCR and Western blot respectively. RESULTS: In vivo, KYD resulted in significantly increased apoptosis of TECs and atrophy of the thymi, especially in the medullary zone. The morphological changes observed in KYD rats were ameliorated by ZGW treatment. Meanwhile, the decreased TMSß4, Tα1, Wnt4, ß-catenin, and Foxn1 levels in KYD rats were also significantly alleviated by ZGW administration. In vitro, elevated TMSß4 and Tα1 levels accompanied with upregulated Wnt4, ß-catenin, and Foxn1 expressions in the TECs were observed after ZGW intervention, however, which were significantly downregulated by ICG-001 supplement. CONCLUSIONS: Maternal kidney-yin deficiency could result in TEC dysfunction in newborn rats. ZGW was able to improve the growth and development of TEC, potentially by regulating the Wnt/ß-catenin pathway.

[Effect of Dendrobium officinale on Yin deficiency constipation induced by warm-drying medicine in mice].

Dendrobium officinale is a sacred product for nourishing Yin and has a clear "thick gastrointestinal" effect. Modern pharmacological studies had found that it could improve gastrointestinal function. This study observed the improvement effect of D. officinale on constipation model mice with Yin deficiency caused by warm-drying medicine. It provided experimental basis for the treatment of Yin deficiency constipation. The male and female ICR mice were randomly divided into normal group, model group, D. officinale high, medium and low dose groups(0.6, 0.4, 0.2 g·kg~(-1)), and phenolphthalein tablets group. The model mice of Yin deficiency constipation were established by gavage with warm-drying medicine. The overall state and body temperature of the mice were observed and recorded. The number of feces, feces weight, fecal moisture content and intestinal propulsion were measured. The morphological damage of colon tissue was observed by hematoxylin-eosin(HE) staining. The expression of inducible nitric oxide synthase(iNOS) in the colon was detected by Western blot and immunohistochemical method. The expression of iNOS mRNA in the colon was detected by Real-time fluorescence quantitative PCR, and the serum cyclic guanosine phosphate(cGMP) level was detected the enzyme-linked immunosorbent assay(ELISA). The results showed that D. candidum could reduce the body temperature of mice with Yin deficiency constipation, increase the number of feces, wet feces, dry feces and intestinal propulsion ability, reduce the expression of iNOS protein and mRNA in the colon, and reduce the content of cGMP in the serum. It showed that D. candidum could improve the symptoms of Yin deficiency constipation mice caused by warm-drying medicine, and the mechanism may be related to reducing the expression of iNOS in the colon and increasing intestinal motility.

Modified Maimendong decoction in the treatment of patients with idiopathic pulmonary fibrosis: Study protocol for a randomized controlled trial.

INTRODUCTION: With dissatisfaction of western medicine, traditional Chinese medicine becomes alternative treatment for idiopathic pulmonary fibrosis patients. The common syndrome of idiopathic pulmonary fibrosis (IPF) is qi and yin deficiency syndrome. The prescription, Modified Maimendong Decoction (MMD), is usually used for IPF patients with qi and yin deficiency syndrome. However, there is no convinced evidence for the efficacy and safety of MMD to treat IPF. METHODS: A double-blind, placebo-controlled, randomized clinical trial was put forward by us. After a 1-day run-in period, 60 eligible patients will be included in the study. These subjects will be allocated to the experiment group or control group in a 1:1 ratio. Patients in the experiment group will take MMD plus Pirfenidone capsule. At the same time, patients in the control group will receive a matched placebo plus Pirfenidone capsule. All subjects will receive 24 weeks of treatment and follow-up period. The primary outcomes are the mean change from the baseline in forced vital capacity and times of acute exacerbations at week 4, 12, 24. Secondary outcomes are the mean change from baseline in the St. George's respiratory questionnaire total score, forced expiratory volume in 1 second percentage/forced vital capacity, diffusing capacity of Carbon monoxide, brain natriuretic peptide, and curative effect of traditional Chinese medicine syndrome at week 4, 12, and 24. Any side effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide the evidence for the effect of MMD in patients with idiopathic pulmonary fibrosis.

[Effect of electroacupuncture combined with Yuyin pill on sex hormone and Th2 cytokines in patients of decreased ovarian reserve function with liver-kidney yin deficiency].

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with Yuyin pill on clinical symptoms, levels of serum sex hormone and Th2 cytokines in patients of decreased ovarian reserve function (DOR) with liver-kidney yin deficiency, and to compare the efficacy between EA combined with Yuyin pill and Yuyin pill alone. METHODS: Sixty patients with DOR were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 1 case dropped off). The patients in the control group were treated with Yuyin pill, 1 pill each time, 3 times a day. Based on the treatment of the control group, the patients in the observation group were additionally treated with acupuncture at Guanyuan (CV 4), Zhongji (CV 3), Guilai (ST 29), Zigong (EX-CA 1), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3) and Taichong (LR 3); EA was applied at bilateral Zusanli (ST 36) and Sanyinjiao (SP 6), with continuous wave, in frequency of 20 Hz and current intensity of 1 to 4 mA, for 20 min. The treatment was given 3 times a week. All the patients terminated treatment during menstrual period, and the treatment was given for 3 continuous menstrual cycles. The menstrual condition score and systemic symptom score were compared between the two groups before and after treatment. The levels of serum sex hormones on 2nd to 3rd day of menstruation, including follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), and the serums levels of interleukin (IL) -4 and IL-10 secreted by Th2 cytokines were compared between the two groups before and after treatment. RESULTS: After the treatment, the menstruation condition scores and systemic symptom scores in the two groups were reduced (P<0.05), and the scores in the observation group were lower than those in the control group (P<0.05). After the treatment, the levels of serum FSH, LH and FSH/LH were reduced (P<0.05), and the E2 levels were increased in the two groups (P<0.05), and the levels of FSH, LH in the observation group were lower than those in the control group (P<0.05), and the E2 level was higher than that in the control group (P<0.05). After the treatment, the levels of serum IL-4 and IL-10 in the two groups were increased (P<0.05), and the levels of IL-4 and IL-10 in the observation group were higher than those in the control group (P<0.05). CONCLUSION: EA combined with Yuyin pill could significantly improve menstruation, systemic symptoms and serum sex hormone levels in patients of decreased ovarian reserve function with liver-kidney yin deficiency, which may restore ovarian function by up-regulating the expression of Th2 cytokines.

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.

Synergistic nourishing 'Yin' effect of iridoid and phenylpropanoid glycosides from Radix Scrophulariae in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Scrophulariae (RS), is a renowned traditional Chinese medicine used as nourishing 'Yin'. The iridoid glycosides (IG) and phenylpropanoid glycosides (PG) are main chemical constituents in RS. However, there had been no pharmacological experiment studies of synergy between IG and PG. Due to the constituents interactions, exploring their synergy profile is of great important for explaining the essence of nourishing 'Yin' efficacy of RS. AIM OF STUDY: The present study was undertaken to evaluate synergistic nourishing 'Yin' effect of IG and PG from RS in vivo and in vitro through their immunoregulation and antioxidant activities. MATERIALS AND METHODS: In this study, IG and PG fractions in RS were isolated and identified by High Performance Liquid Chromatography coupled with tandem quadrupole time-of-flight Mass Spectrometry (HPLC-Q-TOF-MS). The synergistic nourishing 'Yin' effect of two fractions were investigated in vivo and in vitro with thyroxine-induced 'Yin' deficiency (YD) mice model and primary splenic lymphocyte, respectively. The exterior syndrome signs and serologic and cellular biomarkers changes were detected. Then, the synergistic coefficient (SC) of IG and PG on every pharmacodynamics index were calculated by Webb method. RESULTS: Compared with model and mono-therapy group (IG or PG group), IG combined with PG group significantly ameliorated YD by exerting immunoregulation and antioxidant effects. Based on the SC, IG and PG possessed a synergistic effect on heart rate, average speed, upright times, spleen index, LPO, SOD, IL-6, Na+-K+-ATP enzyme in vivo, and cAMP/cGMP, IFN-γ/IL-10, and MDA in vitro with SC > 1. CONCLUSIONS: The nourishing 'Yin' benefits were clearly produced when IG and PG were used in combination, which provided the scientific evidence of multiple-components and multiple-approach synergistic effect of Chinese traditional herbal medicine to control and management of diseases.

[Therapeutic effect and mechanism of three kinds of Dendrobium on constipation in rats with spleen Yin deficiency].

Books on Chinese herbal medicines have shown that Dendrobium has the effect of nourishing Yin and reinforcing Yin,usually used for constipation induced by spleen Yin deficiency in clinical application. D. huoshanense,as an independent species among many species of Dendrobium,has no experimental studies about its effects on spleen Yin deficiency-type constipation. The purpose of this experiment was to illustrate the therapeutic effect of D. huoshanense on the constipation of spleen Yin deficiency type in rats,investigate its preliminary mechanism,and compare it with the D. officinale and D. nobile contained in the Chinese Pharmacopoeia to clarify its characteristics. The spleen Yin deficiency model was replicated in 70 rats by the composite factor method,and then the model rats were randomly divided into 7 groups: model group,Liuwei Dihuang Pills group( LWDHP),D. huoshanense high( DHS-H),medium( DHS-M),low( DHS-L) dose groups,D. nobile group( DNS),and D. officinale group( DOS),and another 10 rats were used as normal group( Normal). After 7 continuous days of administration,the fecal water content and intestine propulsion rate of each group were detected. HE staining was used to observe the pathological damage of ileum and colon in each group. Immunohistochemistry and Western blot were used to detect aquaporin 3( AQP3) expressions,while the expression levels of the somatostatin( SS) and motilin( MTL) in the ileum of each group were detected by enzyme-linked immunosorbent assay. The results showed that as compared with the model group,the rats in each drug-administered group had increased number of fecal pellets,increased fecal water content,and the increased intestinal propulsion rate( P<0. 01),while the pathological damage of the ileum and colon was significantly reduced; the expression of AQP3 protein was significantly decreased( P<0. 01); the level of MTL was significantly increased and the level of SS was decreased( P<0. 01). All DHS groups showed a good dose-effect relationship,and the same dose treatment effect was equivalent to that of DOS,but it was superior to DNS. Therefore,DHS has a significant therapeutic effect on constipation of spleen Yin deficiency type,and its mechanism may be related to intestinal motility and water-liquid metabolism,with a good therapeutic effect.

Characteristics of the traditional Liu-Wei-Di-Huang prescription reassessed in modern pharmacology.

Liu-Wei-Di-Huang (LW) is a Yin nourishing and kidney tonifying prescription in traditional Chinese medicine with promising pharmacological characteristics that can be further exploited and developed in modern medicine. We provide a comprehensive and detailed literature report on the clinical and experimental pharmacology of LW, including its quality control parameters, phytochemistry, pharmacokinetics, and toxicology. Our literature review indicates that the LW prescription possesses a unique combination of pharmacological characteristics that can be safely used for treating very different diseases. Quality control and pharmacokinetic parameters of LW are mostly based on its major bioactive phytochemical constituents. We postulate that modulating or rebalancing the neuroendocrine immunomodulation network in the body is the underlying mechanism of the multiple pharmacological activities displayed by LW.

Broad range metabolomics coupled with network analysis for explaining possible mechanisms of Er-Zhi-Wan in treating liver-kidney Yin deficiency syndrome of Traditional Chinese medicine.

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.

Liuwei Dihuang pill cures postmenopausal osteoporosis with kidney-Yin deficiency: Potential therapeutic targets identified based on gene expression profiling.

This study aimed to investigate the potential therapeutic targets of Liuwei Dihuang pill (LDP) in the treatment of postmenopausal osteoporosis with kidney-Yin deficiency (PMO-KY).Gene expression data were downloaded from the GEO database, including 4 PMO-KY samples and 3 healthy postmenopausal controls from GSE56116, as well as 3 PMO-KY samples before LDP treatment and 3 PMO-KY samples after three months of LDP treatment from GSE57273. Limma package was used to identify differentially expressed genes (DEGs). Afterwards, the potential target genes of LDP (namely key DEGs) were identified according to the comparison of DEGs in PMO-KY group and the DEGs in LDP treatment groups. Subsequently, iRegulon plugin in Cytoscape software was used to predict potential transcription factors (TFs) that regulated the key DEGs, and Comparative Toxicogenomics Database was utilized to identify known PMO-related genes among the key DEGs.Totally, 202 and 2066 DEGs were identified between PMO-KY and controls, as well as after-treatment and before-treatment groups, respectively. Among them, 52 DEGs were up-regulated in PMO-KY but down-regulated after LDP treatment, and 8 TFs were predicted to these DEGs. Furthermore, 34 DEGs were down-regulated in PMO-KY but up-regulated after treatment, and 7 TFs were predicted to regulate these DEGs. Additionally, 43 of the 86 key DEGs were known PMO-related genes.NCOA3, TCF4, DUSP6, PELI2, and STX7 were predicted to be regulated by HOXA13. In the PMO-KY treatment, NCOA3, TCF4, DUSP6, PELI2, and STX7 might be the potential therapeutic targets of LDP. However, further investigation is required to confirm these genes.