Exploring the medication pattern and mechanism of action of traditional Chinese medicine in treating polycystic ovary syndrome with kidney deficiency and blood stasis based on data mining and network pharmacology

Background:Using network pharmacology to explore the potential molecular mechanism of traditional Chinese medicine in treating polycystic ovary syndrome(PCOS)with kidney deficiency and blood stasis syndrome.Method:Collect the related literature materials of PCOS with kidney deficiency and blood stasis syndrome treated by traditional Chinese medicine in four databases in recent ten years,extract the information of prescriptions and complete the frequency analysis.Traditional Chinese Medicine Systems Pharmacology Database was used to screen out the effective components.Use Online Mendelian Inheritance in Man and other databases to screen PCOS disease targets.The intersection targets obtained by clustering prescription and PCOS disease targets were submitted to STRING database for protein-protein interaction network analysis,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathways were analysed by Metascape.Result:There are 155 kinds of traditional Chinese medicines used in the literature.The most commonly utilized ones are Cuscutae Semen,Angelicae Sinensis Radix,and Rehmanniae Radix Praeparata.The results of the cluster analysis indicated that the plants most commonly found throughout the prescription were Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.GO results show that biological processes include cell reaction to organic nitrogen compounds and cell reaction to nitrogen compounds.The functional display of GO molecule includes cytokine receptor binding,signal receptor regulator activity and so on.Kyoto Encyclopedia of Genes and Genomes results show that the possible mechanisms of action are cancer pathway,an endocrine resistance signal pathway.Conclusion:Through data mining,the cluster prescription for PCOS with kidney deficiency and blood stasis syndrome is Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.The network pharmacology research of cluster prescription shows that the main drug components for treating PCOS with kidney deficiency and blood stasis syndrome are quercetin,kaempferol,luteolin,tanshinone IIA,etc.,which act on PTGS2,NCOA2,and other targets,and treat PCOS with kidney deficiency and blood stasis syndrome through cancer and endocrine resistance.

Clinical Nursing Intervention of Moxibustion on Abdominal Distension Symptoms in Heart Failure (Heart and Kidney Yang Deficiency and Blood Stasis Blocking Collaterals Syndrome)

Objective:To investigate the clinical nursing intervention effect of moxibustion on abdominal distension symptoms in heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome).Methods:62 patients with heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome)admitted to our hospital from February 2023 to February 2024 were selected and divided into the observation group(n=31)and the control group(n=31)by using the random numerical table method.The control group adopted conventional nursing interventions,and the observation group received the nursing program of the control group with the addition of moxibustion nursing interventions.The nursing effectiveness,quality of life scores,and nursing satisfaction were compared between the two groups.Results:The nursing effectiveness of the observation group was significantly higher than the control group(P<0.05);the quality of life score of the observation group was significantly higher than the control group(P<0.05);the nursing satisfaction of the observation group was significantly higher than that of the control group(P<0.05).Conclusion:The use of moxibustion nursing intervention in patients with heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome)can effectively relieve the symptoms of abdominal distension,improve patients'quality of life,and increase nursing satisfaction,which has promotion and application values.

Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease

Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.

Observation on Therapeutic Effects of Electroacupuncture on Polycystic Ovary Syndrome of Kidney Deficiency and Phlegm Dampness Type and Oxidative Stress Level

Objective:To observe the clinical effect of electroacupuncture on improving polycystic ovary syndrome(PCOS)of kidney deficiency and phlegm dampness type and serum oxidative stress level.Methods:There were 68 patients with polycystic ovary syndrome were randomly divided into observation group(34 cases)and the control group(34 cases),The observation group was treated by electroacupuncture,while the control group was treated by placebo electroacupuncture.Combined with the evaluation of menstrual cycle,menstrual color,quality,quantity and TCM symptom integral index,the difference of curative effect between the two groups was observed,and the levels of peripheral blood,sex hormones,insulin resistance and oxidative stress were detected before and after treatment for 3 months.Results:The total effective rate in the observation group was better than that in the control group(P<0.01);After intervention,serum LH,FSH,E_(2) and LH/FSH in the observation group were significantly different from those before intervention.The D values of serum LH,FSH,LH/FSH and E_(2) before and after intervention were significantly different between the two groups(P<0.01);Comparing the level of androgen,the serum A4 and T in the observation group were significantly different from those before intervention(P<0.01);After intervention,there was a significant difference in serum A4 and T between the two groups(P<0.01),and there was a significant difference in D value between the two groups before and after intervention;There was a difference in insulin resistance in the observation group before and after intervention(P<0.05),and there was a significant difference in D value between the two groups before and after intervention(P<0.01);After the intervention,the serum SOD,MDA,ROS in the observation group were significantly different from those before the intervention;After intervention,the results of serum SOD and ROS in the observation group were significantly different from those in the control group;There was no significant difference in serum MDA results.There were significant differences in SOD,MDA,ROS between the two groups before and after intervention.Conclusion:Electroacupuncture can improve oxidative stress injury,insulin resistance and hyperandrogenism in PCOS patients.

Proteomics analysis of IBS-D with spleen and kidney yang deficiency

Objective:To investigate the molecular mechanism underlying the development of diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen and kidney yang deficiency (SKYD) using a proteomics approach.Methods:Male Sprague-Dawley rats (n =22) were divided into IBS-D (n =12) and normal control (n =10) groups.SKYD was then modeled in IBS-D rats by a combination of acetic acid enema,bondage,rectal dilation,tail stimulation,and Senna gavage.Colon tissue samples were subsequently collected and examined by Q Exactive mass spectrometry to identify differentially expressed proteins between the two groups.Results:The occurrence of SKYD/IBS-D was associated with ribosomal protein S23 (Rps23),protein phosphatase 2 catalytic subunit alpha (Pp2a),and growth factor receptor-bound protein 2 (Grb2),which are involved in the ribosome,neurotrophin signaling,and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways.Conclusion:These data suggest that SKYD/IBS-D pathophysiology likely involves inflammation,cell growth,apoptosis,stress granule formation,immune activation,loss of epithelial cell integrity,and visceral hypersensitivity.

Age-related changes in prevalence and symptom characteristics in kidney deficiency syndrome with varied health status:a cross-sectional observational study

Objective:This study aimed to reveal the age-related changes in prevalence and symptom characteristics in kidney deficiency syndrome(KDS)with varied health status.Methods:This cross-sectional observational study was conducted in6 hospitals.Investigators queried participants aged 20e79 about their health,including symptoms if any,and completed questionnaires to collect participants responses.Prevalence,severity,and frequency of KDS and other relevant parameters were observed and recorded.Comparative analysis of countable variables,including prevalence,was performed by frequency analysis and c2 test and expressed as a composite ratio.Comparative analysis of quantitative scores of the severity and frequency of symptoms was performed by the rank-sum test.Regression analysis of the correlation of KDS with potential contributing factors was performed by non-conditional binary logistic stepwise regression of numerical variables.Results:Prevalence of KDS in healthy and unhealthy participants correlated with increasing age(P<0.05).In those with chronic disease,KDS prevalence was comparatively high,but the trend was not obvious.KDS prevalence in participants age 20e39 showed an increasing trend with deteriorating health(P<0.05).Compared to healthy individuals,KDS prevalence in subhealthy persons and those with chronic disease showed an increasing trend(P<0.05)in the 40e59 and 60e79 age groups,whereas there was no difference between subhealthy persons and those with chronic disease age 40e59 and 60e79.Symptom severity scores of KDS showed an increasing trend with increasing age and deteriorating health status(P<0.05).Higher symptom frequency scores were also positively correlated with increasing age(P<0.05),but health status deterioration was not significantly correlated(P>0.05).Age,health status,lower back pain,shin soreness or heel pain,tinnitus or deafness,hair loss or loose teeth,incomplete bladder emptying or incontinence,and sexual dysfunction or infertility were potential factors contributing to KDS(P<0.05),but age was the only independent variable for which OR>1.Moreover,the distribution of typical KDS-related symptoms showed dramatic regularities.Conclusion:Prevalence and symptom characteristics of KDS were found to increase consistently with increasing age and deteriorating health status.Kidney deficiency may be an important mechanism of aging in the subhealthy and chronic disease states.

Clinical efficacy of Chinese herbal compound in the treatment of infertility with kidney deficiency:A meta-analysis

Objective:Based on the current evidence system to evaluate the effect of traditional Chinese medicine compound on the clinical efficacy of infertility patients with kidney deficiency.Methods:Search the China Knowledge Resources Database(CNKI),Chinese Science and Technology Journal Database(VIP),China Academic Journal Database(Wanfang),PubMed,EMBASE,Ovid.The included studies are randomized controlled trials.The experimental group is Chinese medicine compound or Chinese medicine compound combined with western medicine,and the control group is western medicine.Two reviewers independently extracted and evaluated the literature data according to the Cochrane manual standards,and used Rev Man5.3 software for data synthesis and Meta-analysis.Results:32 studies were selected,a total of 2715 cases of infertility patients.The clinical pregnancy rate of the experimental group and the control group[n=29,OR(95%CI)=2.47(2.07,2.96),P<0.00001],the clinical total effective rate[n=20,OR(95%CI)=3.77(2.83,5.03),P<0.00001],TCM syndrome score[n=14,MD(95%CI)=4.34(3.08,5.61),P<0.00001],ovulation rate[n=20,OR(95%CI)=2.21(1.85,2.63),P<0.00001],the occurrence rate of two-way BBT[n=11,OR(95%CI)=2.65(2.02,3.48),P<0.00001].The GRADE scoring results show that the level of evidence is low and very low.Conclusion:Traditional Chinese medicine compound can increase the clinical pregnancy rate and clinical total effective rate of infertility with kidney deficiency syndrome,improve the scores of Chinese medical syndromes,increase its ovulation rate and the occurrence rate of BBT bidirectional type,and confirm the clinical efficacy of Chinese medicine compound from the perspective of evidence-based medicine.

Clinical observation on efficacy of compound of warming yang, descending turbidity and dredging collaterals in the treatment of diabetic kidney disease with Yin-Yang deficiency and blood stasis syndrome

Objective:To observe the clinical efficacy of compound of owarming yang,descending turbidity and dredging collaterals in the treatment of diabetic kidney disease with yin-yang deficiency and blood stasis syndrome.Methods:Seventy-six patients of diabetic kidney disease with yin-yang deficiency and blood stasis syndrome were randomly divided into observation group and control group,thirty-eight cases in each group.The control group was given conventional western medicine treatment,while the observation group took compound of owarming yang,descending turbidity and dredging collaterals orally on the basis of conventional western medicine treatment.The course of treatment covered for one month.Before and after treatment,we observed the scores of traditional Chinese medicine symptoms,indicators of renal function[serum creatinine(Scr),blood urea nitrogen(BUN),microalbuminuria(MALB)],indicators of glucose metabolism[fasting plasma glucose(FPG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbAlc)],indicators of hemorheology[plasma viscosity(PV),platelet aggregation rate(PAR),fibrinogen(FIB)],Cystatin-C(Cys-C),C-reactive protein(CRP)in the two groups.Results:After treatment,the clinical effect of the observation group was significantly better than the control group(P<0.05).The scores of traditional Chinese medicine symptoms,indicators of renal function(Scr、BUN、UAER),indicators of glucose metabolism(FPG、2hPG、HbAlc),indicators of hemorheology(PV、PAR、FIB),Cys-C and CRP in the two groups were decreased significantly compared with those before treatment(P<0.05),and the decrease in the observation group was superior to that in the control group(P<0.05).Conclusion:Compound of warming yang,descending turbidity and dredging collaterals has remarkable efficacy in treating of diabetic kidney disease patients with yin-yang deficiency and blood stasis syndrome by alleviating clinical symptoms,glucose metabolism,renal function and microcirculatory disturbance,and the mechanism related to alleviation of microinflammation.

Seasonal climate effect on organ proportion and morbidity in 'Bi-zheng' rats with kidney deficiency syndrome

Objective:Using the traditional Chinese medicine theory of 'Bi-zheng' caused by kidney deficiency,combined with modern medical science and technology,this study assessed the relationships among organ weight,cytokines,pathological manifestations,and traditional Chinese medicine kidney deficiency syndrome in rats with rheumatoid arthritis.Methods:Sixty Sprague-Dawley rats were randomly divided into normal,collagen-induced arthritis (ClA) model,and kidney deficiency arthralgia model groups.Rats in the kidney deficiency arthritis group underwent removal of the testis or ovary and administration of an inflammatory agent.Rats in the control group solely received an inflammatory agent.Type Ⅱ collagen-induced arthritis was induced within 1 week of the winter solstice or summer solstice,in order to sample organs and observe the mental state,posture,fur color,activity level,excrement,body weight,and organ weight of the rats.Results:Compared with the normal and CIA model groups,the kidney deficiency arthralgia model group showed fast and acute onset,prominent symptoms,most obvious potential joint swelling,worst general state,and least amount of weight gain.Compared with the normal group,the proportion of thymus,spleen,and adrenal glands of model rats were larger in winter,with varying degrees of hyperplasia and hypertrophy;these differences were statistically significant (P <.05).In summer,model coefficients were greater than normal in the spleen,while the thymus and adrenal gland coefficients were significantly different between the normal and kidney deficiency arthralgia groups.In summer,the thymus in the kidney deficiency arthralgia group exhibited hypertrophy and hyperplasia,whereas the thymus in the control group did not;this difference was statistically significant (P =.015).Thymus and adrenal gland proportions exhibited seasonal differences in CIA model rats;these were statistically significant (P <.05),with high performance in winter and low performance in summer.The spleen proportion exhibited a trend of high performance in winter and low performance in summer in the kidney deficiency arthralgia model rats.Conclusion:Kidney deficiency is an internal condition linked with the occurrence of arthralgia,and seasonal factors exhibit an impact on the morbidity of arthritis in rats.

Clinical Study of Acupotomy Trinity Lysis on Cervical Spondylotic Myelopathy with Liver and Kidney Deficiency Syndrome

Objective:To compare the therapeutic effects of acupotomy trinity lysis and traditional acupotomy on cervical spondylotic myelopathy.Methods:A total of 205 patients with cervical spondylotic myelopathy of liver and kidney deficiency syndrome were randomly divided into the experimental group(105 cases)and the control group(100 cases).The experimental group was relaxed with acupotomy in three positions:Heaven(tian),Human(ren)and Earth(di).Traditional acupotomy was used to relax Ashi acupoints of the affected vertebra in the control group.One treatment was conducted in one week,and the duration of one course of treatment was three weeks.The VAS,JOA score and NDI index were observed after treatment.Results:Before and after treatment,the total treatment efficiency of the treatment group was 95.23%,and that of the control group was 80.00%,there was significant difference between the two groups,P<0.05;Before operation,there was no significant difference in JOA score,NDI index score,and VAS score between the treatment group and the control group(P>0.05);there was no significant difference after 1 week(P>0.05),but there were significant differences between the two groups 2 weeks and 3 weeks after operation(P<0.05).Conclusion:Acupotomy trinity lysis is a safe,effective and economical treatment for cervical spondylotic myelopathy.

A Novel Approach for Iron Deficiency Anaemia with Liposomal Iron: Concept to Clinic

Iron deficiency anaemia is the most common nutritional deficiency disorder, contributing to 50 percent of all the anaemias in the world. Dietary changes alone are insufficient for the correction and management of iron deficiency anaemia. Hence, iron supplementation is necessary. Conventional oral iron therapy is limited in many patients because of dose dependent side effects, insufficient absorption, lack of compliance and limitation in various inflammatory conditions. Liposomal iron is a technologically designed, innovative form of iron which due to its differential delivery system ensures higher absorption and bioavailability, greater tolerability and least gastro-intestinal side effects unlike conventional oral iron preparations. This review provides a critical discussion and a comprehensive view based on the author’s review of the medical literature concerning the technology of liposomal iron preparation, mechanism of its absorption, its advantage over conventional iron preparations and clinical evidence on its usage in iron deficient states in pregnancy and certain inflammatory conditions.

Role of vitamin D in diabetes mellitus and chronic kidney disease

Approximately 30%-50% of people are recognized to have low levels of vitamin D,and insufficiency and deficiency of vitamin D are recognized as global health problems worldwide.Although the presence of hypovitamin D increases the risk of rickets and fractures,low vitamin D levels are also associated with hypertension,cancer,and cardiovascular disease.In addition,diabetes mellitus(DM) and chronic kidney disease(CKD) are also related to vitamin D levels.Vitamin D deficiency has been linked to onset and progression of DM.Although in patients with DM the relationship between vitamin D and insulin secretion,insulin resistance,and β-cell dysfunction are pointed out,evidence regarding vitamin D levels and DM is contradictory,and well controlled studies are needed.In addition,vitamin D influences the renin-angiotensin system,inflammation,and mineral bone disease,which may be associated with the cause and progression CKD.There is increasing evidence that vitamin D deficiency may be a risk factor for DM and CKD;however,it remains uncertain whether vitamin D deficiency also predisposes to death from DM and CKD.Although at this time,supplementation with vitamin D has not been shown to improve glycemic control or prevent incident DM,clinical trials with sufficient sample size,study periods,and optimal doses of vitamin D supplementation are still needed.This review focuses on the mechanism of vitamin D insufficiency and deficiency in DM or CKD,and discusses the current evidence regarding supplementation with vitamin D in patients with these diseases.

Based on the theory of“Kidney-blood-bone”to explore the mechanism of GH/IGF-1 system in the prevention and treatment of osteoporosis in Qing'e pill

Objective:To observe the changes of growth hormone(GH)/insulin-like growth factor-1(Igf-1)system in blood,kidney and bone tissue of rats,and to explore the preventive and therapeutic effect of Qing'e pill on osteoporosis due to kidney deficiency and its mechanism,to provide the basis for studying the etiology and pathogenesis of osteoporosis due to kidney deficiency.Methods:The rat osteoporosis model was established by ovariectomy,they were randomly divided into normal group,model group,Western Medicine Group,Jianpi Group,high-dose group,middle-dose group and low-dose group,the levels of serum alkaline phosphatase(ALP),tartrate acid phosphatase(TRACP),growth hormone(GH)and GHR(Ghr)in kidney,bone and blood were determined by Elisa,the contents of insulin-like growth factor-1(Igf-1)and insulin-like growth factor-1 receptor(IGF-1R)were analyzed by SPSS 25.0 software.Results:1.Compared with the normal group,the contents of TRACP and ALP in serum of the model group were significantly increased,suggesting that the rats developed highconversion osteoporosis.2.The levels of serum,bone and renal GHR,Igf-1 and insulin-like growth factor-1 receptor(IGF-1R)in the model group were significantly lower than those in the control group.3.Compared with the model group,the contents of TRACP and ALP in the high,middle and low dose groups were significantly decreased.4.Compared with the model group,the contents of GHR,Igf-1 and IGF-1R in blood,bone and kidney tissue of the high,middle and low dose groups were increased.Conclusion:1.Qing'e pill can improve the bone metabolism of osteoporosis.2.Qinge pill may prevent and cure osteoporosis by increasing the contents of GHR,Igf-1 and IGF-1R in blood,bone and kidney.

Effects of Liuwei Dihuang Granule(六味地黄颗粒)on the Outcomes of In Vitro Fertilization Pre-Embryo Transfer in Infertility Women with Kidney-Yin Deficiency Syndrome and the Proteome Expressions in the Follicular Fluid

Objective： To observe the effects of Liuwei Dihuang Granule （六味地黄颗粒, LDG） for tonifying Kidney （Shen） on the outcomes of in v/tro fertilization pre-embryo transfer （IVF-ET） of infertility women with Kidneyyin deficiency syndrome and to explore its mechanism by detecting the proteome expression in the follicular fluid. Methods： Sixty-six infertility patients of Kidney-yin deficiency syndrome who would undergo IVF-ET, were randomly assigned to a treatment group and a control group according to a random number table, 33 cases in each group. Another 33 cases of non-Kidney-yin deficiency syndrome was taken as a syndrome-control group. Besides Westem routine therapy, LDG was given 3 menstrual cycles before IVF to the treatment group, and a placebo granule to the control and syndrome-control groups. The scores of Kidney-yin deficiency symptoms （sore waist and knees, dry vagina, dysphoria with feverish sensation in the chest, palms and soles, etc.） were assessed, the number of retrieved oocytes, rates of high quality oocytes and embryos, fertility rate and clinical pregnancy rate were recorded, and the follicular fluid was collected on the day when the ovum was picked up, the differential protein expression was detected using two-dimensional gel electrophoresis, and then, matrix assisted laser desorption ionization time-of flight mass spectrometry （MALDI-TOF-MS） was applied to identify the proteins. Results： The syndrome score in the treatment group decreased significantly from 16.09 ± 2.58 to 8.67 ± 2.13, while it changed insignificantly in the control group, with a significant difference in the lowering score between the two groups （P〈0.05）; the high quality rates of oocytes and embryos and clinical pregnancy rate were all superior in the treatment group to the control group （82.29% vs 78.08%, 76.76% vs 68.79%, 63.64% vs 36.36%, all P〈0.05）. The protein expression map from the follicular fluid showed that compared with the control group, 33 differential protein expressions were found in the syndrome-control group, among which 18 were down-regulated, and 15 up-regulated; in the treatment group 28 differential protein expressions were found, among which 15 were down-regulated, and 13 up-regulated. Through MALDI-TOF-MS, 14 proteins were identified （P〈0.05）. Conclusions： For the infertility patients undergoing IVF, LDG could alleviate clinical symptoms, improve rates of high quality oocytes and embryos, so as to raise clinical pregnancy rate. The mechanism may be through regulating proteome expression in the follicular fluid to improve the developmental microenvironment for oocytes which would lead to a successful embryo implantation.

Liuwei Dihuang Pill(六味地黄丸)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 （六味地黄丸, 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 proldneticin 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 gone 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 gone 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 gone is an important gone associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gone expression and activation of the JAK/STAT signaling pathway.

Lysine deficiency impaired growth performance and immune response and aggravated inflammatory response of the skin,spleen and head kidney in grown-up grass carp (Ctenopharyngodon idella)

This dissertation was primarily focused on the immune response,inflammatory response and molecular mechanisms in the skin,head kidney and spleen of grown-up grass carp(Ctenopharyngodon idella).Six iso-nitrogen diets differing in lysine concentrations(5.6,8.5,11.6,14.4,17.5 and 20.7 g/kg)were fed to 540 grass carp(164.85±0.79 g)for 60 d.After that,grass carp were challenged by Aeromonas hydrophila for 6 d.This study revealed that lysine deficiency(1)suppressed the growth performa,nce of the fish and decreased their ability to resist skin lesion morbidity,(2)impaired the immune organ s immune response by decreasing the gene expressions of mucin,liver-expressed antimicrobial peptide(LEAP)-2B,β-defensin-1 and LEAP-2A and the production of antibacterial compounds of grown-up grass carp,and(3)aggravated the inflammatory response of immune organs in the fish by increasing the gene expressions of pro-inflammatory cytokines(interferon y2[IFN-γ2],tumor necrosis factorα[TNF-α],interleukin[IL]-15,IL-17D,IL-12p40,IL-6 and IL-8)and down-regulating anti-inflammatory cytokines(IL-11,transforming growth factorβ1[TGF-β1],IL-10 and IL-4/13A),which were tightly correlated with signal transducer and activator of transcription(STAT)1 and STAT3 signaling pathway,respectively.The different phenomenon in the skin,spleen and head kidney of fish may be correlated with the difference in gene subtype.In addition,using quadratic regression analysis of percent weight gain(PWG),skin lesion morbidity,and the lysozyme activities in the spleen and head kidney,the dietary lysine requirements for grown-up grass carp were estimated to be 13.58,13.51,14.56 and 14.18 g/kg,respectively.

Exploring pathogenesis in subjects with subjective Tinnitus having kidney deficiency pattern in terms of Traditional Chinese Medicine based on serum metabolic profiles

OBJECTIVE: To investigate the metabolic pathogenesis in subjects with subjective tinnitus(ST)having kidney deficiency pattern(KDP)(ST/KDP) in terms of Traditional Chinese Medicine.METHODS: Three groups of subjects, including healthy individuals, subjects with ST/KDP, and subjects who were healthy initially and then developed ST/KDP one year later(healthy → ST/KDP),were recruited for this study. Serum metabolic profiles of all subjects were analyzed using ultra-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry. The metabolic characteristics of the ST/KDP subjects were determined, and the corresponding biomarkers were predicted. The metabolomics data from the healthy → ST/KDP subjects were collected for further verification.RESULTS: Twelve metabolites in the ST/KDP subjects were different from those of the healthy control subjects. Of these metabolites, according to the prediction, except for octanoic acid, other metabolites might characterize ST/KDP. Ten metabolites at the outcome ST/KDP stage were different from those at the initial(control) stage. Through the comparison of these metabolites with the predicted metabolites, five common metabolites, including upregulated glutamate, serotonin, oroticacid and 8-oxoguanine, as well as downregulated taurine, were found. These common metabolites were significantly associated with canonical pathways including calcium signaling, γ-aminobutyric acid(GABA) receptor signaling, purine and pyrimidine biosynthesis, taurine biosynthesis, and serotonin receptor signaling.CONCLUSION: The metabolic pathogenesis in ST/KDP subjects was characterized by upregulated glutamate, serotonin, orotic acid and 8-oxoguanine, as well as downregulated taurine, additionally, perturbations of calcium signaling, GABA receptor signaling, purine and pyrimidine biosynthesis, taurine biosynthesis, and serotonin receptor signaling.

The Effect of Hormones of the Hypothalamic-pituitary-target Gland Axes in a Kidney-Yang Deficiency Syndrome Model

Kidney-yang deficiency syndrome(KYDS)is a diagnostic pattern in the traditional Chinese medicine.Studies have shown that KYDS is related to the functional disorder of hormones of the hypothalamic-pituitary-target gland axes.The standard procedure used to mimic KYDS is the injection of a high dose of exogenous glucocorticoid(hydrocortisone and corticosterone).Such a model showed symptoms such as exhaustion,body twists,cold limbs,lying crowded together,decreased rectal temperature,sexual dysfunction,decreased reaction speed,reduced spontaneous activity,hair loss,loss of appetite,and weight loss.Moreover,the model manifested an imbalance in mutual control among the hormones of the pituitary-target gland axes,including adrenocorticotrophic hormone,CORT,CRH,thyroid-stimulating hormone,triiodothyronine,thyroxine,T,E2,follicle-stimulating hormone,luteinizing hormone,and 17-OHCS.

The Fourier Transform Infrared Spectra of the Key Organs Derived from Kidney(Shen)-Yang Deficiency Syndrome Mice

Objective：To explore an approach to rapidly and accurately identify the compounds as biomarkers of Chinese medicine（CM）syndromes.Method：The Fourier transform infrared（FT-IR）spectrometry was applied to investigate the characteristic components of a mice model of Kidney（Shen）-yang deficiency syndrome（KDS）,and the remedial effect of a typical CM formula Shenqi Pill（肾气丸）.Thirty-six females and 18 males of Balb/c mice were randomly divided into KDS,Shenqi or control group.The females and males of the same group freely were mated for 96 h,and the males were taken out and only the female mice were raised.Females of the KDS group were threatened by a ferocious cat every other day for 14 d.After delivery,the KDS,or gestational threatened,offspring were raised at standard condition for 11 weeks.Then 10 male offspring were randomly selected,anaesthetized and their representative organs,i.e.testes,kidneys,lungs and feet were collected,for the FT-IR scan.Mice of the Shenqi group were intragastric administered Shenqi Pill;while mice in the KDS and control groups were given the same volume of saline.Results：The attenuated birth outcomes of the KDS group were displayed.The remarkable FT-IR differences of all organs between KDS mice and healthy control were mainly at 1,735-1,745 cm-1（indicating the increased levels of lipids）and at 1,640-1,647 cm-1and 1,539-1,544 cm-1（displaying the decreased proteins）.No statistic FT-IR difference between Shenqi and control mice was observed.Conclusion：In accordance with major traits of KDS,prenatal stress extensively impaired the building up of proteins and resulting in the excessive lipid storage,and FT-IR could effectively identify the biomarkers of KDS.