She Medicine （畲药） Diren Zishen Formula （地稔滋肾方） Combined with Acupuncture as Adjunctive Treatment for 32 Cases of Primary Biliary Cholangitis with Liver and Kidney Yin Deficiency Syndrome / 中医杂志

ObjectiveTo observe the clinical effectiveness and safety of She medicine （畲药） Diren Zishen Formula（地稔滋肾方） combined with acupuncture as adjunctive treatment for primary biliary cholangitis with liver and kidney yin deficiency syndrome. MethodsSeventy patients of primary biliary cholangitis with liver and kidney yin deficiency syndrome were randomly divided into a control group and a treatment group， with 35 patients in each group. The control group received oral ursodeoxycholic acid capsules （250 mg per dose， three times daily）. The treatment group received She medicine Diren Zishen Formula oral decoction （one dose daily， 200 ml per dose in the morning and evening， served warm） and acupuncture ［bilateral Sanyingjiao （SP6）， Taichong （LR3）， Ganshu （BL18）， Zusanli （ST36）， Fenglong （ST17）， once daily， 5 consecutive days per week］ in addition to the same treatment as the control group. The treatment duration was three months for both groups. Comparisons were made between the two groups before and after treatment for the following parameters， which were four traditional Chinese medicine （TCM） symptoms scores （skin itching， fatigue， jaundice， and flank pain）， TCM syndrome scores， liver function indicators including aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， gamma-glutamyl transferase （GGT） and total bilirubin （TBiL）， liver fibrosis markers including serum laminin （LN）， serum hyaluronic acid （HA）， serum type Ⅳ collagen （Ⅳ-C） and serum type Ⅲ procollagen （PC-Ⅲ）， and inflammatory factor indicators including serum interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α）. The effectiveness of TCM syndrome between the two groups was compared and safety evaluations were also conducted after treatment. ResultsA total of 32 cases were finally analyzed in the treatment group， while the control group had 31 cases. The total effective rate of TCM syndrome in the treatment group （87.50%， 28/32） was higher than that in the control group （67.74%， 20/31） （P＜0.05）. After treatment， the TCM symptom scores， syndrome scores， liver function， and liver fibrosis markers in both groups signi-ficantly decreased， while in the treatment group， the inflammatory factor indicators decreased after treatment， and more decreases were found than those in the control group （P＜0.05 or P＜0.01）. Both groups had good safety， and no adverse reactions were observed. ConclusionThe combination of She medicine Diren Zishen Formula and acupuncture as an adjunctive treatment for primary biliary cholangitis can significantly improve the clinical effectiveness， improve liver function， reduce inflammatory response， and alleviate liver fibrosis， with good safety.

Combined Therapies of Traditional Chinese Medicine Treat Low-prognosis Patients Undergoing IVF-ET Again / 中国实验方剂学杂志

ObjectiveTo objectively evaluate the clinical efficacy of multiple therapies of traditional Chinese medicine （TCM） in low-prognosis patients who received antagonist protocol for in vitro fertilization and embryo transfer （IVF-ET） again. MethodA total of 128 patients with kidney Yin deficiency， liver depression， and blood stasis who planned to receive antagonist protocol for IVF-ET in the West China Second Hospital of Sichuan University were enrolled and assigned into two groups by random number table method. The observation group （64 casces） was treated by oral administration of Chinese medicine decoction + enema of kidney-tonifying and blood-activating method + auricular point sticking + oral administration of dehydroepiandrosterone （DHEA）， while the control group （64 casces） was treated by only oral administration of DHEA. After treatment for three menstrual cycles， both groups received the antagonist protocol for IVF-ET. The TCM syndrome scores， basic sex hormone levels， antral follicle count （AFC）， the usage of gonadotropin （Gn）， endometrial receptivity indicators， embryo quality indicators， and pregnancy outcomes were compared between the two groups. ResultAfter treatment， the observation group showed decreased follicle-stimulating hormone （FSH）/luteinizing hormone （LH） ratio， lowered level of estradiol （E2）， increased AFC， decreased amount and days of Gn usage， improved endometrial receptivity indicators （endometrial thickness on trigger and ET days， proportion of endometrial type A in endometrial types and the level of E2 on trigger day） and embryo quality indicators （the rates of mature follicles， fertilization， normal fertilization， and premium embryos）， and decreased TCM syndrome scores （P<0.05， P<0.01）. Moreover， the observation group had lower FSH/LH ratio， E2 level， and amount of Gn usage， higher AFC， poorer endometrial receptivity and embryo quality indicators， and lower TCM syndrome scores than the control group after treatment （P<0.05， P<0.01）. In addition， except for 3 cases of natural pregnancy， the observation group outperformed the control group in terms of improving the clinical pregnancy rates during initiation cycle and transplantation cycle and clinical pregnancy rate and decreasing biochemical pregnancy rate and early abortion rate （P<0.05）. ConclusionCombined therapies of TCM can alleviate the clinical symptoms， reduce TCM syndrome scores， reduce the Gn usage amount， improve the number and quality of embryos and endometrial receptivity， and coordinate the synchronous development of endometrium and embryo. In this way， they can increase the clinical pregnancy rate and reduce biochemical pregnancy rate and early abortion rate in the low prognosis patients with kidney yin deficiency， liver depression， and blood stasis who are undergoing IVF-ET again.

[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.

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.

Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics / 中国中药杂志

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).

Mechanism of Artemisia annua L. in GIOP with kidney-yin deficiency based on network pharmacology / 药学实践杂志

Objective To predict and preliminarily verify the potential targets and related signaling pathways of Artemisia annua L. in treating glucocorticoid-induced osteoporosis (GIOP) with kidney-yin deficiency by network pharmacology and in vitro experiments. Methods The pharmacological targets of Artemisia annua L. were obtained from TCMSP database and were converted to gene names through Uniprot database. The target genes of GIOP with kidney-yin deficiency were obtained from GeneCards database, OMIM database and Drugbank database, and the common target genes were obtained by cross analysis with drug target gene. Protein-protein interaction (PPI) network was constructed by String database, and visualization analysis and core targets screening were performed by Cytoscape 3.9.0. All common targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis through Metascape database. Finally, the prediction results were verified by in vitro experiments. Results Ninety-eight targets of Artemisia annua L. to GIOP with kidney-yin deficiency were screened, including 17 core genes. The results of GO and KEGG functional enrichment analysis indicated that Artemisia annua L. treating GIOP with kidney-yin deficiency was related to biological processes such as hormonal response, positive regulation of cell death and extracellular stimulation response, et al, as well as signaling pathways such as PI3K/AKT, AGE/RAGE, MAPK and IL-17 et al. The number of genes enriched in PI3K/AKT signaling pathway was the largest. In vitro experiment results showed that Artemisia annua L. promoted the proliferation of osteoblasts damaged by dexamethasone (DEX), increased alkaline phosphatase activity, activated PI3K/AKT pathway, and promoted the phosphorylation of AKT. Conclusion Artemisia annua L. treating GIOP with kidney-yin deficiency has the characteristics of multi-targets and multi-pathway, which could promote the proliferation and differentiation of osteoblasts through multiple pathways. The PI3K/AKT signaling pathway is an important pathway. Artemisia annua L. treating GIOP with kidney-yin deficiency might be related to its ability to promote the PI3K/AKT signaling pathway and promote the phosphorylation of AKT.

Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway / 中国中药杂志

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.

Pharmacokinetics and pharmacodynamics of Astragali Radix-Corni Fructus Herb-pair Extract, in kidney-yin deficiency model

Abstract To investigate the pharmacokinetics and pharmacodynamics of Astragali Radix-Corni Fructus herb-pair in kidney-yin deficiency model, which was made by continuously oral gavage of thyroxine. A simple and rapid LC-MS/MS method was developed and validated for the determination of loganin and morroniside in rat plasma and used for the pharmacokinetics study. The kidney-yin deficiency significantly changed the AUC(0-∞), Cmax and CLz/F of loganin and morroniside. The T1/2z of morroniside increased significantly in the kidney-yin deficiency rats. For the pharmacodynamics study, the liver index, kidney index, and ALT, TBIL, UREA, CREA level in the kidney-yin deficiency mice were examined. The herb-pair had been proved to be effective for the treatment of kidney-yin deficiency by affecting the liver, kidney, ALT, UREA and CREA, which showed positively correlated with the dose. The pharmacokinetics and pharmacodynamics studies in the pathological status could offer more valuable information for the future application of Astragali Radix-Corni Fructus herb-pair.

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.

A Case Report of Infant Alopecia Areata Successfully Treated with Rokumigan Modified Formula / 日本東洋医学雑誌

We report a case of a 3-year-old girl who suffered from alopecia areata and was successfully treated with rokumigan modified formula. Initially, alopecia areata appeared on her left temporal region at the age of 3. The hair loss range had spread rapidly over the whole head. She visited our Kampo clinic because of insufficient effect of antiallergic drug. We prescribed her yokukansan, shimotsuto and juzentaihoto but the effect was insufficient. Finally, we thought this might be caused by kidney yin deficiency and liver blood deficiency because she had symptoms of pale white complexion, fine pulse, pale tongue with thin fur, and night sweating. Therefore, we administered rokumigan modified formula : rokumigan, tokiinshi and lycium fruit. Her hair began to grow after administering this formulation. There was not the re-hair loss during taking medicine for about 4 months. According to the traditional Chinese medicine, alopecia areata can be classified into 4 types : blood heat type, blood stasis type, dual deficiency type of yin and blood, dual deficiency type of qi and blood. We diagnosed this case as a dual deficiency type of yin and blood and selected rokumigan modified formula. Rokumigan is effective for various symptoms of kidney yin deficiency, and rokumigan modified formula may be useful for the treatment of infant alopecia areata.

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.

[Reproduction-related proteins differentially expressed in the testes of the mice with kidney-yang or kidney-yin deficiency].

OBJECTIVE: To compare the differentially expressed proteins in mice with kidney-yang deficiency and those with kidney-yin deficiency induced by hydrocortisone, and explore the similar and different material bases of male infertility caused by the two types of kidney deficiency. METHODS: Thirty Kunming mice were equally randomized into a normal control, a kidney-yang deficiency and a kidney-yin deficiency group. The animals of the normal control group were injected intraperitoneally with normal saline at 0.2 ml qd for 7 days, while those of the latter two groups with hydrocortisone at 25 mg/kg/d for 10 days and 50 mg/kg/d for 7 days, respectively, for establishment of kidney-yang deficiency and kidney-yin deficiency models. Then the pathological changes in the testicular tissue of the mice were observed by HE staining and the differentially expressed proteins were compared among different groups using isobaric tags for relative and absolute quantitation (iTRAQ) and the bioinformatics method. RESULTS: Sod1 was found to be a reproduction-related node protein differentially expressed in the testis tissues of the two types of kidney-deficiency mice, more highly expressed in the kidney-yin than in the kidney-yang deficiency group (P < 0.05). Five reproduction-associated node proteins were co-expressed in the testes of the two groups of kidney-deficiency mice, with significantly up-regulated expression of Rps28 and down-regulated expressions of Rpl11, Rplp2, Svs2 and Svs3a (P < 0.01). CONCLUSIONS: Sod1 may be one of the key material bases for the differentiation of male infertility caused by kidney-yang deficiency from that induced by kidney-yin deficiency, while Rps28, Rpl11, Rplp2, Svs2 and Svs3a may be the common material bases of male infertility caused by the two types of kidney deficiency.

Effect of Yangjing Zhongyu Tang in Treating Kidney-Yin Deficiency Due to Repeated Implantation Failure and on LIF,VEGF,IL-1β,MCP-1 Levels / 中国实验方剂学杂志

Objective:To explore the clinical efficacy of Yangjing Zhongyu Tang in treating kidney-Yin deficiency due to repeated implantation failure (RIF). Method:Totally 70 patients with kidney yin deficiency due to repeated implantation failure (RIF) who received the periodic Frozen thawed embyo (FET) after in vitro fertilization (IVF) embryo cryopreservation were selected from the Integrative Medicine Reproductive and Genetics Center of Affiliated Hospital of Shandong University of Traditional Chinese Medicine(TCM). They were randomly divided into observation group and control group, with 35 cases in each group. All patients were received long protocol controlled ovarian hyperstimulation. Observation group was given Yangjing Zhongyu Tang from the 5th day to the 14th day of the menstrual cycle 1 month before transplantation, and continued to take it on the 5th day of the menstrual cycle in the month of the transplantation. Control group did not given TCM. After treatment, TCM syndrome scores, endometrial thickness, typing, uterine artery pulsation index (PI) and resistance index (RI) of HCG, endometrial secretion leukemia inhibitory factor (LIF), blood vessels endothelial growth factor (VEGF), interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1), number of eggs obtained, fertilization rate and embryo transfer results were observed. Result:After treatment, the scores of TCM syndromes in observation group were significantly improved, with statistically significant difference (PPPβ and LIF of observation group were higher than those of control group, and the MCP-1 was lower than that of control group (PPConclusion:Yangjing Zhongyu Tang can significantly alleviate the clinical symptoms of patients with kidney-Yin deficiency due to RIF, effectively improve the type A endometrial morphology of RIF patients, reduce the uterine artery blood flow resistance, optimize endometrial implantation, and significantly improve the clinical pregnancy rate.

Influence of Addition and Subtraction Therapy of Guyinjian to Ovarian Reserve Function for Patients with Poor Ovarian Response with Kidney Yin Deficiency Syndrome / 中国实验方剂学杂志

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.

Observation of Addition and Subtraction Therapy of Liuwei Dihuangwan Combined with Huanglian Ejiaotang to Primary Insomnia in Elderly Liver and Kidney Yin Deficiency Syndrome / 中国实验方剂学杂志

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.

Clinical Observation on Modified Huqianwan in Treatment of Rheumatoid Arthritis Liver-kidney Yin Deficiency Syndrome / 中国实验方剂学杂志

Objective: To explore the clinical efficacy and safety of modified Huqianwan in treatment of rheumatoid arthritis (RA) liver-kidney Yin deficiency syndrome, and investigate its possible mechanism. Method: A total of 184 patients with RA liver-kidney Yin deficiency syndrome were randomly divided into Chinese medicine group (62 cases), western medicine group (57 cases) and integrated Chinese and western medicine group (65 cases) according to the digital table method. The patients in Chinese medicine group were treated with Huqianwan; the patients in western medicine group were treated with methotrexate tablets and leflunomide tablets; and the patients in integrated Chinese and western medicine group received Huqianwan+methotrexate tablets and leflunomide tablets,with a treatment course of 12 weeks in all groups. The pain visual analog scale (VAS), swelling and tenderness scores of 28 joints (DAS28), average hands grip strength, morning stiffness time and liver-kidney Yin deficiency syndrome differentiation of traditional Chinese medicine (TCM) syndrome score were compared between groups before and after treatment. The changes of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), immunoglobulin (Ig) G, tumor necrosis factor-alpha (TNF-α) and rheumatoid factor (RF) were detected in all groups after treatment. Clinical efficacy, and incidence of adverse reactions such as gastrointestinal response, liver injury, leukopenia, serum glutamate oxaloacetic aminotransferase (GOT) and platelet (PLT) level changes were compared between the groups, so as to investigate the efficiency and safety of the different medicines. Result: After 12 weeks of treatment, the total clinical effective rate was 79.0%, 80.7%, and 92.3% respectively in Chinese medicine group, western medicine group, and integrated Chinese and western medicine group; the integrated Chinese and western medicine group was significantly better than the Chinese medicine group and western medicine group (PPPPConclusion: The efficacy in treating RA liver and kidney Yin deficiency syndrome shows no significant difference between modified Huqianwan and methotrexate tablets+leflunomide tablets. In the treatment of RA liver and kidney Yin deficiency syndrome, Huqianwan has fewer adverse reactions. Huqianwan combined with methotrexate tablets+leflunomide tablets is superior to that in methotrexate tablets+leflunomide tablets in treatment of RA liver-kidney Yin deficiency syndrome.

Reproduction-related proteins differentially expressed in the testes of the mice with kidney-yang or kidney-yin deficiency / 中华男科学杂志

Objective@#To compare the differentially expressed proteins in mice with kidney-yang deficiency and those with kidney-yin deficiency induced by hydrocortisone, and explore the similar and different material bases of male infertility caused by the two types of kidney deficiency.@*METHODS@#Thirty Kunming mice were equally randomized into a normal control, a kidney-yang deficiency and a kidney-yin deficiency group. The animals of the normal control group were injected intraperitoneally with normal saline at 0.2 ml qd for 7 days, while those of the latter two groups with hydrocortisone at 25 mg/kg/d for 10 days and 50 mg/kg/d for 7 days, respectively, for establishment of kidney-yang deficiency and kidney-yin deficiency models. Then the pathological changes in the testicular tissue of the mice were observed by HE staining and the differentially expressed proteins were compared among different groups using isobaric tags for relative and absolute quantitation (iTRAQ) and the bioinformatics method.@*RESULTS@#Sod1 was found to be a reproduction-related node protein differentially expressed in the testis tissues of the two types of kidney-deficiency mice, more highly expressed in the kidney-yin than in the kidney-yang deficiency group (P < 0.05). Five reproduction-associated node proteins were co-expressed in the testes of the two groups of kidney-deficiency mice, with significantly up-regulated expression of Rps28 and down-regulated expressions of Rpl11, Rplp2, Svs2 and Svs3a (P < 0.01).@*CONCLUSIONS@#Sod1 may be one of the key material bases for the differentiation of male infertility caused by kidney-yang deficiency from that induced by kidney-yin deficiency, while Rps28, Rpl11, Rplp2, Svs2 and Svs3a may be the common material bases of male infertility caused by the two types of kidney deficiency.

Liuwei Dihuang Pill () Treats Postmenopausal Osteoporosis with Shen (Kidney) Yin Deficiency via Janus Kinase/Signal Transducer and Activator of Transcription Signal Pathway by Up-regulating Cardiotrophin-Like Cytokine Factor 1 Expression.

OBJECTIVES: To investigate the mechanism of Liuwei Dihuang Pill (, LDP) in treating postmenopausal osteoporosis (PMOP) with Shen (Kidney) yin deficiency. METHODS: In this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group (Group A), PMOP Shen-yang deficiency group (Group B), PMOP without Shen deficiency group (Group C), and control group (Group N). Real-time polymerase chain reaction (RT-PCR) and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 (CLCF1), ankyrin repeat and SOCS box containing 1 (ASB1), and prokineticin 2 (PROK2) genes and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. RESULTS: The mRNA (P<0.05) and protein (P<0.01) expression levels of the CLCF1 gene in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gene were obviously up-regulated (P<0.01). After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated (both P<0.01), and the average bone density of the top femur had significantly increased (P<0.05). In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3. CONCLUSIONS: The CLCF1 gene is an important gene associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gene expression and activation of the JAK/STAT signaling pathway.

Clinical effects of Qingrun Yangmu Oral Liquid combined with artificial tears on dry eye visual fatigue patients due to Liver-Kidney Yin Deficiency Syndrome / 中成药

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.