Clinical Study of Modified Shenqi Pill （肾气丸） Plus Tongdu Tiaoshen Acupuncture （通督调神针刺） for Neurogenic Bladder After Spinal Cord Injury of Kidney-Yang Deficiency Syndrome / 中医杂志

ObjectiveTo observe the clinical efficacy of modified Shenqi Pill （肾气丸） plus Tongdu Tiaoshen Acupuncture （通督调神针刺） in the treatment of neurogenic bladder after spinal cord injury of kidney-yang deficiency syndrome. MethodsForty-six patients were randomly divided into 23 cases each in the control group and the treatment group. Both groups were given conventional treatment， i.e. oral methylcobalamin tablets （0.5 mg each time， 3 times a day） and paraplegic conventional acupuncture （once a day， 6 consecutive days a week）. The control group was given simple bladder function rehabilitation training on the basis of the conventional treatment； and the treatment group was given modified Shenqi Pill orally （1 dose a day， 150 ml each time， taken warmly in morning and evening） and Tongdu Tiaoshen Acupuncture （once a day， 6 consecutive days per week） in addition to what were given to the control group. The treatment course lasted for 4 weeks. The 24 h urination frequency， 24 h urine leakage frequency， 24 h single urine volume， bladder residual urine volume， international lower urinary tract symptom （LUTS） score， traditional Chinese medicine （TCM） syndrome score were compared between the two groups， and clinical effectiveness and TCM syndrome effectiveness were compared between the two groups after treatment. ResultsTwenty patients in each group were finally analyzed in this study. The number of 24 h urination， the number of 24 h urine leakage， bladder residual urine volume， LUTS score， and the TCM syndrome scores decreased after treatment in both groups， and the 24 h single urine volume increased （P＜0.01）； and much more improvement was found of each index in the treatment group than in the control group （P＜0.05 or P＜0.01）. The total clinical effectiveness and TCM syndrome effectiveness in the treatment group was 85.00% （17/20） respectively， which were statistically significantly higher than 45.00% （the total clinical effectiveness， 9/20） and 60.00% （TCM syndrome effectiveness， 12/20） in the control group （P＜0.01）. ConclusionModified Shenqi Pill plus Tongdu Tiaoshen Acupuncture can signi-ficantly improve the clinical symptoms of neurogenic bladder patients after spinal cord injury of kidney-yang deficiency syndrome， having better effectiveness than simple bladder function rehabilitation training， and its mechanism may be related to the improvement of the injured nerve function innervating the bladder.

Association between Yang Deficiency Syndrome and the End-point Events of Diabetic Kidney Disease： A Retrospective Cohort Study / 中医杂志

ObjectiveTo investigate the impact of yang deficiency syndrome on the progression to end-point events of diabetic kidney disease （DKD）. MethodsA retrospective study among patients with stage Ⅳ DKD admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from September 1st， 2016 to September 30th， 2021 was conducted. Data on the patients' general information， clinical indicators including duration of diabetes， duration of proteinuria， history of smoking and drinking， hemoglobin （HGB）， fasting blood glucose （FBG）， albumin （ALB）， serum creatinine （Scr）， urea nitrogen （BUN）， uric acid （UA）， cholesterol （TC） ， triglycerides （TG）， low-density lipoprotein （LDL）， 24-hour urine protein quantification （24h-UTP） and estimated glomerular filtration rate （eGFR）， and TCM syndromes including symptoms， tongue and pulse， and syndrome scores were collected. The patients were divided into exposure group （yang-deficiency group） and non-exposure group （non-yang-deficiency group）. The general information， clinical indicators and incidence rates of end-point events were compared， and the impact of yang deficiency syndrome on the end-point events of stage Ⅳ DKD was analyzed. Survival analysis was performed using Kaplan-Meier method， and multivariate Cox proportional risk models were used to identify independent predictors of end-point events. ResultsA total of 160 patients with stage Ⅳ DKD were included in the study， including 43 cases of yang deficiency syndrome and 117 cases of non-yang deficiency syndrome. Compared to those in the non-yang deficiency group， the waist circumference， BUN and the incidence of end-point events in the yang deficiency group were significantly higher （P＜0.05 or P＜0.01）. Spearman correlation analysis showed that yang deficiency syndrome was positively correlated with incidence of end-point events of stage Ⅳ DKD （r = 0.167， P = 0.035）. Furthermore， 24h-UTP and BUN levels were also positively correlated with end-point events in stage Ⅳ DKD patients （P＜0.01）， while ALB and HGB levels were negatively correlated （P＜0.01）. Kaplan-Meier survival curves showed that yang deficiency syndrome was associated with an increased risk of end-point events （Log Rank P = 0.011）. Moreover， 24h-UTP levels ≥3500 mg， BUN level ≥8 mmol/L， ALB level ＜30 g and HGB level ＜11 g were all associated with the increase of the risk of end-point events （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that yang deficiency syndrome was an independent risk factor for patients with stage Ⅳ DKD to progress into end-point events （HR = 2.36， 1.32 to 4.21； P = 0.004）， as well as 24h-UTP ≥ 3500 mg， BUN ≥ 8 mmol/L， HGB＜11 g and ALB＜30 g （P＜0.05 or P＜0.01）. ConclusionsFor stage Ⅳ DKD， patients with yang deficiency syndrome are more likely to have end-point events， which is an independent risk factor for the progression into end-point events.

Vascular Cognitive Impairment with Kidney Yang Deficiency Syndrome and DNA Methylation Essence / 中国实验方剂学杂志

ObjectiveTo investigate the distribution of vascular cognitive impairment （VCI） with kidney Yang deficiency syndrome and explore the biological nature of VCI with kidney Yang deficiency syndrome from the perspective of DNA methylation under the combination of disease and syndrome， so as to provide an epigenetic target for traditional Chinese medicine （TCM） treatment of this disease with this syndrome in the future. MethodCommunity residents in Beijing were screened out for cognitive impairment from September 2020 to November 2022 through the scale， and VCI patients were analyzed for the syndrome. VCI patients with kidney Yang deficiency syndrome and healthy people were enrolled in this study. Peripheral venous blood was collected and subjected to genome-wide DNA methylation detection by Illumina Human Methylation 850K BeadChip. Then， differentially methylated genes （DMGs） were screened out for bioinformatics analysis. ResultA total of 1 902 people were investigated in this study， and 201 of them had VCI， accounting for 10.57%， including 72.14% with kidney Yang deficiency syndrome. The methylation results showed that compared with the normal group， the VCI group had 386 differential methylation sites， and 136 DMGs were annotated. The Kyoto Encyclopedia of Gene and Genomes（KEGG） signaling pathway enrichment analysis showed that the DMGs between the two groups were mainly involved in mammalian target of rapamycin（mTOR） signaling pathway， Estrogen signaling pathway， cyclic adenosine monophosphate（cAMP） signaling pathway， etc. Protein-protein interaction （PPI） analysis showed that DMGs， such as epidermal growth factor receptor（EGFR）， epidermal growth factor （EGF）， and signal transducer and activator of transcription 3（STAT3）， played important roles in the network. ConclusionKidney Yang deficiency is the main syndrome in VCI patients. DMGs including EGFR， EGF， and STAT3 and the related pathways such as mTOR signaling pathway， Estrogen signaling pathway， and cAMP signaling pathway may play a vital role in the occurrence and development of VCI with kidney Yang deficiency syndrome.

Constructing a Syndrome Differentiation Model by Combining Latent Structure Analysis of Association Rules： An Example of Kidney Yang Deficiency Syndrome in Primary Osteoporosis / 中医杂志

ObjectiveTo construct a quantitative differentiation model of traditional Chinese medicine （TCM） syndromes by taking primary osteoporosis （POP） with kidney yang deficiency syndrome as an example， and to provide methodological reference for the standardization of syndrome differentiation. MethodsHigh-frequency clinical features of POP were screened by descriptive statistical analysis， and strong association features of POP were obtained by association rule algorithm. On this basis， a latent structure （latent tree） model was established through latent structure analysis， and the implicit and explicit variables （features） related to POP with kidney yang deficiency syndrome were comprehensively clustered， and the clustering results were interpreted by the indexes of mutual information and cumulative information coverage， to explore the primary and secondary symptoms， and to deduce the categories of POP with kidney yang deficiency syndrome based on the probability of the features appearing in the various latent categories. Based on the categories， the clinical feature scores and identification thresholds were calculated， and the syndrome differentiation model of POP with kidney yang deficiency was initially constructed by combining the comprehensive judgment rules. Finally， the results of TCM professionals' judgment were used as the gold standard to further evaluate the effectiveness of the model in assisting the syndrome differentiation. ResultsThe 32 features strongly associated with POP were obtained， and the Bayes information critedon score of the further constructed latent tree model was -15291.93. Based on the mutual information and the cumulative information coverage， the main symptoms of POP with kidney yang deficiency syndrome were bone weakness， fatigue， pale tongue， clear urine， frequent nocturnal urination， cold limbs， thin pulse， white coating， and secondary symptoms were weakness， loss of libido， loose stool， frequent urination， lumbar and knee weakness， and fear of cold. From the probability of the occurrence of each clinical feature in different latent categories of POP with kidney yang deficiency syndrome， the state was introduced as S0 category （none/mild kidney yang syndrome）/ S1 category （moderate kidney yang syndrome）/ S2 category （severe kidney yang syndrome）. Optimizing the preliminary rules of state identification and refining the state of S1 category， the results showed that among 970 patients with POP， there were 520 patients having no/mild kidney yang deficiency syndrome， 224 patients with moderate to mild kidney yang deficiency syndrome， 81 patients with moderate to severe kidney yang deficiency syndrome， and 145 patients with severe kidney yang deficiency syndrome. During the evaluation and validation process， the correct rate of the model assessment index was 0.8835， while the sensitivity was 0.7181， and the specificity was 0.9437. ConclusionCombined with the latent structure analysis of the association rule， the syndrome differentiation model for POP with kidney yang deficiency could be constructed， and the model shows a good quantitative identification effect， which can provide methodological supports for clinicians to improve the efficiency and accuracy of TCM diagnosis.

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).

Study on the objectivity and biological mechanism of Psoralea corylifolia Linn.'s 'Great dryness damages the liver' / 药学学报

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Quantitative Analysis of Syndromes in 558 Cases of Kidney Yang Deficiency Syndrome Based on Factor Analysis / 世界科学技术-中医药现代化

Objective Through factor analysis of the quantified syndrome information of 558 cases of kidney yang deficiency syndrome,the constructing feature of kidney yang deficiency syndrome was revealed,which provides clinical data support for the objectification,standardization and normalization of kidney Yang deficiency syndrome.Methods Firstly,the frequency analysis of symptoms,tongue and pulse signs of 558 patients with kidney Yang deficiency syndrome was carried out,and then the main syndrome information of the patients with kidney Yang deficiency syndrome was quantified.Finally,the common factors and their representative variables of kidney Yang deficiency syndrome were screened out through factor analysis,and the constructing feature of kidney Yang deficiency syndrome was analyzed combined with TCM syndrome knowledge.Results Eight common factors with eigenvalues greater than 1 were extracted by principal component analysis,and the cumulative contribution rate was 60.483%.After the factor rotation,the representative variables with the absolute value of load coefficient greater than 0.45 in each common factor were selected.The representative variables of F1 are afraid of cold and fond of warmth(0.947)and intolerance to cold(0.932).The representative variables of F2 are waist pain(0.754),waist and knee weakness(0.720)and cold in waist and knees(0.466).The representative variables of F3 are depression(0.749),insomnia(0.711)and diarrhoea(0.470).The representative variables of F4 are thin fur(0.819)and white fur(0.768).The representative variable of F5 are tinnitus and deafness(0.687),frequent nocturnal urination(0.591)and decreased libido(0.587).The representative variables of F6 are pulse sinking(0.766)and pulse weakness(0.736).The representative variables of F7 is thready pulse(0.942).The representative variable of F8 is pale tongue(0.961).External syndrome of disease location involved in these common factors are waist,bone,brain,ear,anterior Yin,posterior Yin and reproductive function.The disease nature involved in these common factors is deficiency and cold.Conclusion The basic constituent units of kidney Yang deficiency syndrome include disease location syndrome elements and disease nature syndrome elements.The disease location is kidney,and the abnormal changes of kidney location are mainly external symptoms of waist,bone,brain,ear,anterior Yin,posterior Yin and reproductive function.Its disease nature is deficiency and cold.Yang deficiency leads to external cold.Yang Qi deficiency can not warm the body surface resulting in the appearance of external cold syndrome.

Mechanism of Zhenwu Decoction in improving renal inflammatory injury in mice with DN of spleen-kidney Yang deficiency syndrome by regulating ROCK/IKK/NF-κB pathway / 中国中药杂志

To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1β, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.

Identification of Kidney-Yang Deficiency Syndrome in Osteoporosis Patients Based on Rule Ensemble Method of Bagging Combining LASSO Regression / 中国实验方剂学杂志

ObjectiveTo investigate the identification of kidney Yang deficiency syndrome of patients with osteoporosis（OP）， and to form the clinical syndrome identification rules of traditional Chinese medicine（TCM）. MethodBasic information， etiology， clinical symptoms and other characteristics of 982 OP patients were included， and statistical tests were used to screen the variables associated with kidney Yang deficiency syndrome. Taking the decision tree as the base model， bootstrap aggregation algorithm（Bagging algorithm） was utilized to establish the classification model of kidney Yang deficiency syndrome in OP， generating numerous rules and removing redundancy. Combining least absolute shrinkage and selection operator（LASSO） regression to screen key rules and integrate them to construct an identification model， achieving the identification of kidney Yang deficiency syndrome in OP patients. ResultEighteen key identification rules were screened out， and of these， where 11 rules with regression coefficients>0 correlated positively with the kidney Yang deficiency syndrome， the rule with the highest coefficient was chilliness（present）&feverish sensation over the palm and sole（absent）. The other 7 rules with regression coefficients<0 correlated negatively with the syndrome， the rule with the lowest coefficient was reddish tongue（present）&diarrhea（absent）&deficiency of endowment（absent）. According to the regression coefficients of each key rule， variables with importance>0.2 were ranked as chilliness， reddish tongue， feverish sensation over the palm and sole， cold limbs， clear urine， diarrhea， deficiency of endowment， prolonged illness. The results of the partial dependence analysis of the identification model showed that compared to OP patients without chilliness， those with chilliness（present） had a 0.266 8 higher probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identification of the syndrome. Similarly， compared to OP patients without reddish tongue， those with reddish tongue had a 0.141 9 lower probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identifying non-kidney Yang deficiency syndrome. The accuracy， sensitivity， specificity and area under receiver operating characteristic curve（AUC） of the established kidney Yang deficiency syndrome identification model in the test set were 0.865 9， 0.853 7， 0.872 0 and 0.931 5， respectively. ConclusionA precise identification model of OP kidney Yang deficiency syndrome is conducted basing on the rule ensemble method of Bagging combining LASSO regression， and the screened key rules can explain the identification process of kidney Yang deficiency syndrome. In this research， according to the regression coefficients of rules， the importance and partial dependence of variables， combined with the thinking of TCM， the influence of patient characteristics on the identification of syndromes is described， so as to reveal the primary and secondary syndromes of identification and assist the clinical identification of kidney Yang deficiency syndrome.

Correlations of Characteristics of Kidney Yang Deficiency Syndrome with Clinical Indicators and Risk Factors of Chronic Kidney Disease / 中国实验方剂学杂志

ObjectiveTo study the correlations of the characteristics of kidney Yang deficiency syndrome in patients with chronic kidney disease （CKD） with clinical indicators and to explore the risk factors of kidney Yang deficiency in CKD. MethodThe differentiation of traditional Chinese medicine （TCM） syndrome classified the 225 CKD patients who met the inclusion criteria into two groups： one group of kidney Yang deficiency syndrome （99 patients） and one group of non-kidney Yang deficiency syndrome （126 patients）. The symptoms， tongue manifestation， pulse manifestation， and accompanied symptoms of the kidney Yang deficiency syndrome group were recorded. The syndrome characteristics were summarized by factor analysis and clustering analysis. The levels of hemoglobin, red blood cell count, urinary protein, urinary glucose, creatinine, urea nitrogen and glomerular filtration rate were compared between the kidney Yang deficiency syndrome group, the non-kidney Yang deficiency syndrome group and the normal control group by ANOVA and non-parametric test. The binary logistic regression model was employed to analyze the correlations of lifestyle， body mass index （BMI） with syndrome. ResultThe high-frequency symptoms of CKD patients with kidney Yang deficiency syndrome were waist pain， fear of cold， favor of warm， lethargy， fear of cold at waist and knees， etc. The patients mainly presented deep pulse， thready pulse， or weak pulse， and the tongue with white coating， greasy coating， or thin coating. A total of 13 common factors were obtained， which can be classified into 5 categories. The patients with kidney Yang deficiency syndrome mainly had symptoms in limbs （especially lower limbs）， chest， bladder， fleshy exterior， and stomach， with the main manifestations of deficiency-cold， Qi deficiency， fluid retention， and blood stasis. The clustering analysis classified the patients into 11 categories， which reflected that kidney Yang deficiency syndrome mainly presented the symptoms of Qi deficiency， blood stasis， and fluid retention， with fleshy exterior， limbs， spleen， stomach， ears， mind， and bladder involved. The results of clustering analysis and factor analysis were consistent， both of which indicated that the patients were weak with deficiency-cold， accompanied by fluid retention and blood stasis. Frequency analysis also showed that common symptoms mainly included Qi deficiency， fluid retention， cold-dampness， and blood stasis. Compared with the non-kidney Yang deficiency group， the kidney Yang deficiency group showed a large proportion of patients in stage 3-5 CKD， elevated urea nitrogen （P<0.05）， decreased glomerular filtration rate， hemoglobin， and red blood cell count （P<0.05）， and increased qualitative grade of urine protein. In addition， the results of regression analysis showed that female， little or no exercise， and diet preference were the risk factors for kidney Yang deficiency syndrome in CKD （P<0.05）. ConclusionThe disease location and manifestations have correspondence in the CKD patients with kidney Yang deficiency syndrome. The TCM symptoms are correlated with clinical indicators. Hemoglobin， red blood cell count， glomerular filtration rate， urea nitrogen， and urine protein can reflect the connotation of kidney Yang deficiency syndrome in CKD to a certain extent. Additionally， related risk factors in life can affect the occurrence of kidney Yang deficiency syndrome in CKD.

Correlations of Characteristics of Kidney Yang Deficiency Syndrome with Clinical Indicators and Risk Factors of Chronic Kidney Disease / 中国实验方剂学杂志

ObjectiveTo study the correlations of the characteristics of kidney Yang deficiency syndrome in patients with chronic kidney disease （CKD） with clinical indicators and to explore the risk factors of kidney Yang deficiency in CKD. MethodThe differentiation of traditional Chinese medicine （TCM） syndrome classified the 225 CKD patients who met the inclusion criteria into two groups： one group of kidney Yang deficiency syndrome （99 patients） and one group of non-kidney Yang deficiency syndrome （126 patients）. The symptoms， tongue manifestation， pulse manifestation， and accompanied symptoms of the kidney Yang deficiency syndrome group were recorded. The syndrome characteristics were summarized by factor analysis and clustering analysis. The levels of hemoglobin, red blood cell count, urinary protein, urinary glucose, creatinine, urea nitrogen and glomerular filtration rate were compared between the kidney Yang deficiency syndrome group, the non-kidney Yang deficiency syndrome group and the normal control group by ANOVA and non-parametric test. The binary logistic regression model was employed to analyze the correlations of lifestyle， body mass index （BMI） with syndrome. ResultThe high-frequency symptoms of CKD patients with kidney Yang deficiency syndrome were waist pain， fear of cold， favor of warm， lethargy， fear of cold at waist and knees， etc. The patients mainly presented deep pulse， thready pulse， or weak pulse， and the tongue with white coating， greasy coating， or thin coating. A total of 13 common factors were obtained， which can be classified into 5 categories. The patients with kidney Yang deficiency syndrome mainly had symptoms in limbs （especially lower limbs）， chest， bladder， fleshy exterior， and stomach， with the main manifestations of deficiency-cold， Qi deficiency， fluid retention， and blood stasis. The clustering analysis classified the patients into 11 categories， which reflected that kidney Yang deficiency syndrome mainly presented the symptoms of Qi deficiency， blood stasis， and fluid retention， with fleshy exterior， limbs， spleen， stomach， ears， mind， and bladder involved. The results of clustering analysis and factor analysis were consistent， both of which indicated that the patients were weak with deficiency-cold， accompanied by fluid retention and blood stasis. Frequency analysis also showed that common symptoms mainly included Qi deficiency， fluid retention， cold-dampness， and blood stasis. Compared with the non-kidney Yang deficiency group， the kidney Yang deficiency group showed a large proportion of patients in stage 3-5 CKD， elevated urea nitrogen （P<0.05）， decreased glomerular filtration rate， hemoglobin， and red blood cell count （P<0.05）， and increased qualitative grade of urine protein. In addition， the results of regression analysis showed that female， little or no exercise， and diet preference were the risk factors for kidney Yang deficiency syndrome in CKD （P<0.05）. ConclusionThe disease location and manifestations have correspondence in the CKD patients with kidney Yang deficiency syndrome. The TCM symptoms are correlated with clinical indicators. Hemoglobin， red blood cell count， glomerular filtration rate， urea nitrogen， and urine protein can reflect the connotation of kidney Yang deficiency syndrome in CKD to a certain extent. Additionally， related risk factors in life can affect the occurrence of kidney Yang deficiency syndrome in CKD.

Clinical Efficacy of Modified Jingui Shenqitang in Treatment of Renal Hypertension with Spleen-kidney Yang Deficiency Syndrome / 中国实验方剂学杂志

Objective::To explore the efficacy of modified Jingui Shenqitang in the treatment of renal hypertension with spleen-kidney yang deficiency syndrome and its effect on blood lipids, renal function and vascular endothelial function. Method::Totally 110 patients were randomly divided into control group and observation group by random number table method, with 55 cases in each group. Control group was given levamlodipine (2.5-5 mg every time, once/day) and enalapril maleate (10 mg every time, once/day), and observation group was given modified Jingui Shenqitang in addition to the therapy of control group (1 dose/day). They were treated for 12 weeks. Blood pressure monitoring was performed, the systolic blood pressure (SBD) and diastolic blood pressure (DBP) were compared before and after treatment, and the blood pressure compliance was calculated. The 24 h urinary protein quantification (24 hUpr), serum creatinine (SCr), albumin (ALB) and urea nitrogen (BUN) were detected before and after treatment, the glomerular filtration rate (eGFR) was calculated, and the triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HLD-C) and low-density lipoprotein( LDL-C) were detected before and after treatment. The spleen-kidney Yang deficiency syndromes were scored before and after treatment. The levels of nitric oxide (NO), plasma endothelin (ET) and angiotensin Ⅱ (Ang Ⅱ) were detected before and after treatment. Result::The blood pressure efficacy in observation group was better than that in control group (Z=1.905, P<0.05). The efficacy of traditional Chinese medicine(TCM) syndromes in observation group was better than that in control group (Z=2.416, P<0.01). The compliance rate of causal blood pressure in observation group was higher than that in control group (88.89% vs 71.25%) (χ2=7.861, P<0.01). SBP and DBP in observation group were lower than those in control group (P<0.05). TC and LDL-C in observation group were lower than those in control group (P<0.01). The 24 hUpr, BUN and SCr in observation group were lower than those in control group (P<0.05), while the eGFR was higher than that in control group (P<0.05). The levels of ET-1 and Ang Ⅱ in observation group were lower than those in control group (P<0.05), whereas the NO level was higher than that in control group (P<0.01). Conclusion::In addition to the routine intervention with western medicine, modified Jingui Shenqitang for patients with spleen-kidney Yang deficiency syndrome can further control blood pressure level, improve blood pressure compliance rate, regulate lipid metabolism, protect kidney function, and regulate vascular endothelial function, with a better clinical efficacy than pure western medicine.

Effect of Wenshen Zhuyang Tiaozhou Method on Sex Hormones, Insulin and Ovulation in PCOS Patients with Kidney-Yang Deficiency Syndrome Based on PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

Objective::To investigate the effect of Wenshen Zhuyang Tiaozhou method on sex hormones, insulin and ovulation in polycystic ovary syndrome (PCOS) patients with kidney-Yang deficiency syndrome based on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Method::Totally 60 PCOS patients with kidney-Yang deficiency syndrome treated at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from February 2017 to July 2018 were selected and divided into observation group and control group according to the random number table method, with 30 cases in each group. The control group was orally treated with ethinylestradiol and cycloproterone acetate tablets, in addition to this therapy, the observation group also received Wenshen Zhuyang Tiaozhou method. Both groups were followed up after three months of treatment. Sex hormone levels, fasting plasma glucose (FPG) and fasting insulin (FINS) levels were measured in all patients. Homeostasis model assessment-insulin resistance(HOMA-IR) was calculated by homeostasis model assessment method, and the expression levels of Akt and p-Akt proteins in endometrium were detected by Western blot. Result::After treatment, the levels of FSH and LH in both groups decreased, and the level of E2 sex hormone increased (P<0.05). After treatment, the levels of FSH and LH in observation group were lower than those in control group, whereas the level of E2 sex hormone was higher than that in control group (P<0.05). After treatment, the levels of FPG and FINS in two groups were significantly lower (P<0.05), while the levels of FPG and FINS in observation group were significantly lower than those in control group (P<0.05). After treatment, the ovarian volume and the number of sinusoidal oocytes in two groups decreased significantly, while the endometrial thickness increased (P<0.05). After treatment, the ovarian volume and the number of sinusoidal oocytes in observation group were significantly lower than those in control group, and the endometrial thickness was significantly lower than that in observation group (P<0.05). After treatment, the ovarian volume and the number of sinusoidal oocytes in observation group were significantly lower than those in control group, and the endometrial thickness was larger than that of control group (P<0.05). After treatment, the Akt and p-Akt proteins in the endometrium of observation group and control group were significantly decreased, while the Akt and p-Akt proteins in the endometrium of observation group were significantly lower than those of control group (P<0.05). Conclusion::Wenshen Zhuyang Tiaozhou method can effectively ameliorate the sex hormone level, regulate insulin and promote the recovery of ovarian function in PCOS patients with kidney-Yang deficiency syndrome. This may be related to the blocking of the phosphorylation of Akt and the inhibition of the activation of PI3K/Akt signaling pathway.

Effect of Yinfupian and Yangfupian on Brown Adipose Tissue of Yang Deficiency Mice / 中国实验方剂学杂志

Objective:To observe the expression of brown adipose tissue (BAT), cells, proteins and corresponding genes in Yang deficiency model mice induced by Rhei Radix et Rhizoma suspension, and to explore the thermogenesis of processed products of Aconiti Lateralis Radix Praeparata with Jianchang faction characteristics. Method:Twenty mice, half male and half female, were randomly selected as the normal female and male groups. And the other 80 mice were administrated with Rhei Radix et Rhizoma suspension (the content of 0.25 g·mL-1) to establish Yang deficiency model, after the model was established, they were randomly divided into the model female and male groups, female and male groups of Shengfupian, female and male groups of Yinfupian, female and male groups of Yangfupian, 10 mice in each group. Mice were intragastric administrated with corresponding medical solution for two weeks (1.54 g·kg-1·d-1) according to groups. Normal group and model group were given equal volume distilled water. After administration, BAT of scapular region of mice was collected and the changes of BAT cells were observed by hematoxylin-eosin (HE) staining. The expression of uncoupling protein 1 (UCP1) and its mRNA were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result:Compared with the normal group of the same sex, the proportion of BAT in the model group decreased significantly (P<0.01). Compared with the model group of the same sex, the proportion of BAT in female mice from Shengfupian and Yinfupian groups increased significantly (P<0.01), while there was no significant difference between each administration group and model group in the male mice. Compared with normal mice of the same sex, there were many scattered vacuoles in BAT cells of the model group, and fewer cells could be observed due to larger vacuoles. Compared with the model group of the same sex, BAT cells in mice from the Shengfupian group showed fewer vacuoles, smaller cells and tight arrangement, the density of BAT cells in mice from the Yangfupian group also increased significantly, while the vacuoles in BAT cells of mice from the Yinfupian group decreased relatively and the cells did not increase significantly. Compared with the same sex mice, the expression level of UCP1 in the model group and the normal group was statistically significant (P<0.05, P<0.01). In the female mice, the expression level of UCP1 in Yangfupian group was significantly higher than that in the model group (P<0.05), each administration group of male mice was significantly different from that of the model group of the same sex (P<0.05), of which Yangfupian was the most significant. The relative expression of UCP1 mRNA in the model group was significantly lower than that in the normal group of the same sex (P<0.05, P<0.01). In the female mice, compared with the model group, the relative expression levels of UCP1 mRNA in Yangfupian group, Shengfupian group and Yinfupian group increased significantly (P<0.05, P<0.01), compared with Yangfupian group, the relative expression levels of UCP1 mRNA in Shengfupian and Yinfupian were also significantly different (P<0.05). In the male mice, compared with the model group, the relative expression of UCP1 mRNA in Yangfupian group was significantly increased (P<0.01), but there was no significant difference in Shengfupian group and Yinfupian group, in addition, compared with Yangfupian group, the relative expression of UCP1 mRNA in Shengfupian group and Yinfupian group had significant difference (P<0.05). Conclusion:Shengfupian, Yinfupian and Yangfupian all have obvious improvement on Yang deficiency syndrome induced by Rhei Radix et Rhizoma suspension. The mechanism may be to promote the expression of UCP1 protein and its mRNA and enhance the activity of BAT. And the effect of Yangfupian is the best.

Clinical observation of main symptoms relief by Chinese Jing Liqueur in patients with Kidney Yang Deficiency Syndrome / 中成药

AIM To investigate the efficacy and safety of Chinese Jing Liqueur (Curculiginis Rhizoma,Angelicae sinensis Radix,Cistanches Herba,etc.) in relieving main symptoms of patients with Kidney Yang Deficiency Syndrome.METHODS Within eight-week trial,one hundred and twenty patients randomly and equally assigned to control group and experimental group took 50 mL Chinese Jing Liqueur and 50 mL 10％ diluted Chinese Jing Liqueur,respectively.The grading scale for Kidney Yang Deficiency Syndrome and change curve for body surface temperature after drinking were established on day 0,the 4th week day and the 8th week day.The blood samples were collected for blood hemorheologies detection as well.An array of measurements before and after drinking,the Kidney Yang Deficiency Syndrome scores,single symptom scores,body surface temperature and hemorheologies between the two groups were thus compared.RESULTS The experimental group displayed a significantly higher clinical cure rate (31.034％) than the control group (5.172％) (P =0.000),total effective rate (69.966％)than the control group (34.483％) (P =0.000).The experimental group didn't compromise its superiority to the control group if evaluated by improvement in chilly sensation and the cold limbs (35.593％ to 6.667％,P =0.000);and by the fibrinogen level [(2.845 ± 0.724) g/L to (2.500 ± 0.395) g/L,P =0.004)].No significant difference in incidence of adverse reactions between the two groups was observed (P =0.619).Meanwhile,Chinese Jing Liqueur's power in improving the patients' fatigue and weakness of waist and knees,hyposexuality,listlessness,nocturia and lower extremity edema was noticed as well.CONCLUSION For patients with Kidney Yang Deficiency Syndrome,Chinese Jing Liqueur proves its efficacy in improving their main symptoms through enhancing the basic skin temperature and prolonging the duration of skin temperature rise.

Effect of Acaí (Euterpe oleracea) on biological expression characteristics of deficiency-heat and deficiency-cold rats / 中国中药杂志

To study the effects of Acaí on biological expression characteristics in rats with deficiency-heat and deficiency-cold syndromes, SD rats were divided into blank group, deficiency-heat model group, deficiency-heat+Phellodendri Chinensis Cortex group, deficiency-heat+Acaí high dose and low dose groups, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Acaí high dose and low dose groups. The rats were treated with intramuscular injection of hydrocortisone (20 mg•kg⁻¹) or dexamethasone sodium phosphate (0.35 mg•kg⁻¹) for 21 days to set up deficiency-heat model and deficiency-cold models. The levels of cAMP, cGMP, T3, T4 and rT3 were detected by radioimmunoassay. The levels of TP, UA, TC, TG and ALB were detected by colorimetry. The level of cAMP, cAMP/cGMP in serum were reduced in Acaí high dose group (P<0.05, P<0.001). The levels of T3, T4 and rT3 were significantly reduced in the Acaí high dose group (P<0.01, P<0.001, P<0.05). The levels of TP, UA, TC, TG and ALB were significantly reduced in the Acaí high dose group (P<0.001, P<0.05, P<0.05, P<0.05, P<0.01). However, Acaí had no obvious effects on deficiency-cold models. Acaí showed the same effect with Phellodendri Chinensis Cortex in adjusting the levels of deficiency-heat rats; but unlike Cinnamomi Cortex, Acaí showed no obvious effects in adjusting the levels of deficiency-cold rats.

Chinmedomics strategy to discover effective constituents and elucidate action mechanism of Nanshi capsule against kidney-yang deficiency syndrome / 中国中药杂志

The chinmedomics method was used to explore the effect of Nanshi capsule on endogenous metabolites of rats with kidney-yang deficiency syndrome, investigate the metabolites and metabolic pathways closely related to kidney-yang deficiency syndrome (KYDS)and identify the therapeutic basis of Nanshi capsule(NPC)as well as its action mechanism for KYDS. The routine biochemical indexes of serum were detected and histomorphology was observed. Based on the chinmedomics technology platform, discriminatory analysis in multivariate modes was conducted for rat blood and urine, thus to investigate the biomarkers of KYDS and the therapeutic effect of NPC against KYDS. Meanwhile, the main constituents of NPC in rat serum were also detected to analyze its correlation between the constituents in vivo and the biomarkers of KYDS, and determine the potential effective compounds for therapeutic effect. Eleven biomarkers of KYDS were identified in the rat models, involving steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism. It was found that NPC could regulate steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism; PCMS analysis showed that caffeic acid, 2-hydroxy-1-methoxy-anthraquinone, 1-hydroxy-2-methoxyanthraquinone, ferulic acid glucuronide conjugation, deacetylasperulosidic acid, cynaroside, betaine and umbelliferone were the main effective compounds of NPC for KYDS. In this study, cynaroside, betaine, umbelliferone and other compounds in NPC could integrally regulate the disturbance of metabolic profile in KYDS by improving the hormone synthesis, hormone synthesis pathway, hormone synthesis and release pathway in tyrosine metabolism and linoleic acid synthesis pathway in linoleic acid metabolism. These results indicated that the NPC had the characteristics of multi-pathway, multi-target and overall regulation in the treatment of KYDS. Chinmedomics approach can provide methodology support to discover innovative drug from traditional Chinese medicine.

Clinical Observation of Yang-supplementing Fire Moxibustion for Chronic Obstructive Pulmonary Disease in Stable Stage / 上海针灸杂志

Objective To observe the clinical efficacy of yang-supplementing fire moxibustion in treating chronic obstructive pulmonary disease (COPD) in stable stage. Method Totally 120 COPD patients of yang deficiency type in stable stage were divided into 3 groups by the random number table, a yang-supplementing fire moxibustion group (yang-supplementing group), a dry mild moxibustion group (mild moxibustion group), and a regular Western medication group (regular group), 40 cases in each group, and 30-day treatment was taken as a course. They were treated and observed for a course, followed by a 3-month follow-up study. The pulmonary function indexes, yang-deficiency signs, quality of life, and comprehensive therapeutic efficacy were observed in the three groups. Result After treatment, the pulmonary function indexes, yang deficiency signs, quality of life, and comprehensive therapeutic efficacy were significantly improved in the three groups (P<0.01); the percent of predicted forced expiratory volume in one second (FEV1%) and yang deficiency signs were significantly improved after intervention in the mild moxibustion group (P<0.05); meanwhile, the quality of life was also significantly improved after intervention in the mild moxibustion group and regular group (P<0.01); the therapeutic efficacy of the yang-supplementing group was better than that of the mild moxibustion group and regular group, and the efficacy of the mild moxibustion group was better than that of the regular group. Conclusion Yang-supplementing fire moxibustion can improve the pulmonary function, postpone the progressive decrease of pulmonary function, significantly improve the yang deficiency constitution, enhance the quality of life and comprehensive therapeutic efficacy in treating yang-deficient COPD patients in stable stage.

Clinical Observation of Yang-supplementing Fire Moxibustion for Cancer-induced Fatigue of Yang-deficiency Type / 上海针灸杂志

Objective To observe the clinical efficacy of yang-supplementing moxibustion in treating cancer-induced fatigue of yang-deficiency type. Method Seventy-five patients with cancer-induced fatigue of yang-deficiency type were randomized into 3 groups by using random number table: yang-supplementing fire moxibustion group, fire therapy group, and a conventional control group, 25 patients in each group. The improvements of fatigue, quality of life and traditional Chinese medicine (TCM) syndrome were observed. Result The three treatment protocols were all effective in improving fatigue, quality of life and TCM syndrome, and the effects of yang-supplementing fire moxibustion were more significant than the other two treatments, and that of fire therapy group was superior to that of the conventional control group. Conclusion Yang-supplementing fire moxibustion can effectively improve fatigue, yang-deficiency symptoms, and the quality of life in cancer-induced fatigue of yang-deficiency type.

An investigation on clinical therapeutic effect of acupoint injection combined with health education for treatment of spleen kidney yang deficiency syndrome in patients with chronic obstructive pulmonary disease at stable stage / 中国中西医结合急救杂志

Objective To observe the clinical efficacy of Chuankezhi acupoint injection combined with nursing health care education for treatment of patients with chronic obstructive pulmonary disease (COPD) at stable stage complicated with spleen kidney deficiency syndrome.Methods A prospective study was conducted. 118 patients with stable COPD and spleen kidney yang deficiency syndrome admitted to Hangzhou Third People's Hospital and Zhejiang Xinhua Hospital from February to April 2014 were enrolled, and they were divided into an experimental group (60 cases) and a control group (58 cases) according to the random number table. Both groups were given conventional treatment [including oxygen therapy, bronchodilators, corticosteroids, rehabilitation therapy in accord with the Global Initiative COPD (GOLD)]. Simultaneously, in the experimental group, Chuankezhi acupoint injection was additionally given, once daily for 12 weeks, and appropriate corresponding health education was mentioned. The lung function, quality of life and prognoses of the patients were regularly followed up for 9 months and compared between the two groups.Results After 12 weeks, one second forced expiratory volume (FEV1), FEV1/forced vital capacity (FVC) and maximum voluntary ventilation (MVV) per minute in the experimental group were significantly higher than those in control group [FEV1 (L): 1.57±0.42 vs. 1.35±0.35, FEV1/FVC: (58.62±4.56)% vs. (50.36±4.35)%, MVV (L/min): 60.62±7.56 vs. 56.95±6.33, allP < 0.05]. The quality of life evaluation form for COPD (QLICD-COPD) was used to evaluate the physical function, psychological function, social function and specific modules scores, showing that the above items in the experimental group were significantly higher than those in control group (total score: 74.69±8.92 vs. 68.62±8.95, physical function score: 74.16±8.55 vs. 66.31±7.15, mental function score: 78.69±9.79 vs. 72.64±8.45, social function score: 75.45±6.75 vs. 70.36±6.12, specific modules score: 67.52±6.33 vs. 61.36±6.17, allP < 0.05); Barthel index score was also significantly higher than that in the control group (75.41±9.24 vs. 68.43±7.95,P < 0.05). Within 9 months of follow-up, the incidence of acute exacerbation of COPD in the experimental group was significantly lower than that in the control group [5.00% (3/60) vs. 17.24% (10/58),P < 0.05]. The re-admission rate was also significantly less in patients in experimental group compared with that of control group [1.67% (1/60) vs. 12.07% (7/58),P < 0.05]. Conclusion Chuankezhi acupoint injection with health education for treatment of patients with COPD at stable stage and spleen kidney yang deficiency syndrome has good clinical efficacy, worthy to be applied more widely.