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1.
Journal of Traditional Chinese Medicine ; (12): 192-197, 2024.
Article in Chinese | WPRIM | ID: wpr-1005370

ABSTRACT

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.

2.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 97-103, 2023.
Article in Chinese | WPRIM | ID: wpr-953928

ABSTRACT

ObjectiveTo observe the clinical efficacy of herb-partitioned moxibustion on the navel combined with Yishen Tongluo prescription in the treatment of infertility induced by idiopathic asthenozoospermia (iAZS) with kidney-Yang deficiency and collateral obstruction syndrome and its effect on sperm DNA damage and superoxide dismutase (SOD) in the seminal plasma. MethodsA total of 112 eligible patients who met the inclusion criteria were randomly divided into an observation group (56 cases) and a control group (56 cases). The patients in the observation group were treated with herb-partitioned moxibustion on the navel combined with Yishen Tongluo prescription,while those in the control group received levocarnitine oral liquid. The primary observation indicators included spouse pregnancy rate,progressive motility (PR),and total sperm motility,and the secondary observation indicators included sperm DNA fragmentation index (DFI),SOD in the seminal plasma, and improvement of TCM syndromes. The treatment cycle was 12 weeks. Before and after treatment,the PR,total sperm motility,sperm DFI,SOD in the seminal plasma, and TCM syndrome scores were recorded. The patients were followed up for 12 weeks and the pregnancy status of spouses within 24 weeks (half a year) was recorded. The clinical efficacy of the two groups was evaluated. ResultThe pregnancy rate of spouses in the observation group was 15.69% (8/51), higher than 3.85% (2/52) in the control group (χ2=4.118,P<0.05). The total effective rate of the observation group was 88.24%(45/51), superior to 69.23% (36/52)in the control group (Z=-3.402,P<0.01). After treatment, PR, total sperm motility,sperm DFI, SOD in the seminal plasma, and TCM syndromes of the two groups were improved compared with those before treatment (P<0.05), and the observation group was superior to the control group (P<0.05). ConclusionHerb-partitioned moxibustion on the navel combined with Yishen Tongluo prescription in the treatment of iAZS-induced infertility patients with kidney-Yang deficiency and collateral obstruction syndrome can increase PR,total sperm motility, and SOD level in the seminal plasma, reduce sperm DFI,improve the TCM symptoms of patients, and improve the pregnancy rate of spouses. The mechanism may be attributed to the fact that this treatment can increase the SOD level in the seminal plasma of patients,enhance the body's antioxidant function,protect sperm from oxidative stress damage,and reduce sperm DFI.

3.
Journal of Traditional Chinese Medicine ; (12): 2033-2036, 2023.
Article in Chinese | WPRIM | ID: wpr-988810

ABSTRACT

It is believed that the key pathogenesis of endometriosis combined with infertility is spleen and kidney yang deficiency and binding of dampness and stasis, for which the method of warming yang and removing turbidity is advocated, and self-made Wenyang Huazhuo Formula (温阳化浊方) is recommended with flexibility by stages in accordance with the rules of the changes of yin and yang in the menstrual cycle and the storing and drainage of uterus. Specifically, during the menstruation, it is suggested to warm channels and invigorate blood, drain dampness and remove dampness; during the late menstruation, the method of warming yang and replenishing yin, regulating and supplementing the chong mai (冲脉) and ren mai (任脉); for inter-menstruation period, it is advised to warm yang and replenish qi, rectify qi and harmonize blood; in terms of premenstrual period, the method of warming and supplementing spleen and kidney, warming uterus and assisting in fertility can be used. Accordingly, Formulas at the menstruation stage, follicular stage, ovulation stage, and luteal stage to warm yang and remove turbidity are recommended in their modifications, respectively.

4.
China Pharmacy ; (12): 671-677, 2023.
Article in Chinese | WPRIM | ID: wpr-965503

ABSTRACT

OBJECTIVE To investigate the effects of Wenyang jieyu decoction on phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and neurotransmitters in rats with kidney-yang deficiency depression. METHODS The SD rats were divided into blank group, model group, fluoxetine group (positive control of western medicine, 4.17 mg/kg), Xiaoyao powder group (positive control of TCM, 1.88 g/kg) and Wenyang jieyu decoction low-dose, medium-dose and high-dose groups (1.25, 2.50, 5.00 g/kg), with 15 rats in each group. Except for blank group, the other groups were treated with corticosterone 20 mg/kg subcutaneously to induce kidney-yang deficiency depressed model, meanwhile the mice were given relevant medicine intragastrically, once a day, for 28 consecutive days. The general conditions of rats were observed. The sucrose preference rate and the static time of forced swimming were detected, and organ indexes of rats were calculated. The levels/contents of neurotransmitters in serum were detected, the expressions of PI3K/Akt pathway-related proteins in hippocampus were detected, and the number of dendritic spines was determined. RESULTS Compared with blank group, model group suffered from the symptoms such as hair loss, fear of cold, curling up; sucrose preference rate, indexes of adrenal gland, thymus gland and spleen,serum levels of cyclic adenosine phosphate (cAMP), brain-derived neurotrophic factor and gamma-aminobutyric acid, the ratio of cAMP to cyclic guanosine monophosphate, the contents of norepinephrine, dopamine and 5-hydroxy-tryptamine, the expressions of PI3K, Akt, mammalian target of rapamycin, and the number of dendritic spines in the hippocampus were significantly decreased (P<0.01). The time of immobility, level of glutamic acid and protein expression of glycogen synthetase kinase-3β were prolonged and increased (P<0.01). Compared with model group, depression symptoms of rats in each administration group were improved, and the above indexes were mostly reversed (P<0.05 or P<0.01). CONCLUSIONS Wenyang jieyu decoction can improve depression-like behavior and the deficiency of kidney-yang, regulate the secretion of neurotransmitters, and activate PI3K/Akt signaling pathway, thus playing a role in protecting hippocampal neurons.

5.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 111-119, 2023.
Article in Chinese | WPRIM | ID: wpr-961690

ABSTRACT

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.

6.
China Journal of Chinese Materia Medica ; (24): 3664-3677, 2023.
Article in Chinese | WPRIM | ID: wpr-981496

ABSTRACT

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).

7.
China Journal of Chinese Materia Medica ; (24): 3032-3038, 2023.
Article in Chinese | WPRIM | ID: wpr-981433

ABSTRACT

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.


Subject(s)
Male , Mice , Animals , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Liver Glycogen , Yang Deficiency/drug therapy , Yin Deficiency/drug therapy , Kidney , Body Weight
8.
Chinese Acupuncture & Moxibustion ; (12): 45-50, 2023.
Article in Chinese | WPRIM | ID: wpr-969946

ABSTRACT

OBJECTIVE@#To observe the effect of fire needling on prostate symptoms, quality of life, average daily number of nightly urination, urine flow rate and prostat volume in patients with mild to moderate benign prostatic hyperplasia (BPH) of kidney yang deficiency.@*METHODS@#A total of 60 patients with mild to moderate BPH of kidney yang deficiency were randomly divided into an observation group (30 cases, 3 cases dropped off) and a control group (30 cases, 4 cases dropped off). The observation group was treated with fire needling at Guanyuan (CV 4), Shuidao (ST 28) and Qugu (CV 2) twice a week (2-3 d interval between each treatment), continuous treatment for 4 weeks. The control group received lifestyle advice and education, once a week for 4 weeks. In the two groups, the international prostate symptom score (IPSS), the quality of life (QoL) score and the average daily number of nightly urination were observed before treatment, after treatment and during the follow-up of the 4th week; the urinary maximum flow rate (Qmax), the average flow rate (Qave), and the prostate volume were assessed before and after treatment in the two groups. The safety was observed in the observation group.@*RESULTS@#After treatment and during follow-up, the IPSS scores, QoL scores, and the average daily number of nightly urination in the observation group were decreased compared with those before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). After treatment, there was no significant difference in Qmax, Qave and prostate volume between the two groups and within the each group (P>0.05). There were no fire needling-related adverse reactions, and no obvious abnormality was found in urine routine and coagulation function tests before and after treatment in the observation group.@*CONCLUSION@#Fire needling can improve lower urinary tract symptoms and quality of life, reduce frequency of nightly urination in patients with mild to moderate BPH of kidney yang deficiency, and has good safety.


Subject(s)
Male , Humans , Prostatic Hyperplasia/therapy , Quality of Life , Yang Deficiency , Treatment Outcome , Kidney
9.
Chinese Acupuncture & Moxibustion ; (12): 14-18, 2023.
Article in Chinese | WPRIM | ID: wpr-969940

ABSTRACT

OBJECTIVE@#To compare the therapeutic efficacy of governor vessel moxibustion combined with fluoxetine hydrochloride capsule, simple fluoxetine hydrochloride capsule and placebo moxibustion combined with fluoxetine hydrochloride capsule for mild to moderate depression with kidney-yang deficiency.@*METHODS@#A total of 126 patients with mild to moderate depression with kidney-yang deficiency were randomized into a governor vessel moxibustion group (42 cases, 2 cases dropped off), a western medication group (42 cases, 1 case dropped off) and a placebo moxibustion group (42 cases, 1 case dropped off). The western medication group was given fluoxetine hydrochloride capsule orally, 20 mg a time, once a day. On the basis of the treatment in the western medication group, governor vessel moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) in the governor vessel moxibustion group, once a week; placebo moxibustion was applied in the placebo moxibustion group, once a week. Treatment of 8 weeks was required in the 3 groups. Before and after treatment, the scores of Hamilton depression scale-17 (HAMD-17), Asberg's rating scale for side effects (SERS) and TCM clinical symptom were compared, and the clinical efficacy was evaluated.@*RESULTS@#After treatment, the scores of HAMD-17, SERS and TCM clinical symptom were decreased compared before treatment in the 3 groups (P<0.05), the decrease ranges of above scores in the governor vessel moxibustion group were larger than those in the western medication group and the placebo moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the governor vessel moxibustion group, which was higher than 75.6% (31/41) in the western medication group and 80.5% (33/41) in the placebo moxibustion group (P<0.05).@*CONCLUSION@#Governor vessel moxibustion combined with fluoxetine hydrochloride capsule can improve the degree of depression and relieve the clinical symptoms in mild to moderate depression patients with kidney-yang deficiency, the efficacy is superior to simple fluoxetine hydrochloride capsule, and can reduce the fluoxetine hydrochloride capsule-induced adverse effect to a certain extent.


Subject(s)
Humans , Moxibustion , Yang Deficiency/drug therapy , Depression/etiology , Fluoxetine , Acupuncture Points , Kidney
10.
Journal of Traditional Chinese Medicine ; (12): 2522-2531, 2023.
Article in Chinese | WPRIM | ID: wpr-1003897

ABSTRACT

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.

11.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 150-157, 2023.
Article in Chinese | WPRIM | ID: wpr-997668

ABSTRACT

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.

12.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 141-150, 2023.
Article in Chinese | WPRIM | ID: wpr-972296

ABSTRACT

ObjectiveTo analyze the characteristics of kidney Yang deficiency syndrome in different stages and time evolution of chronic kidney disease (CKD) to explore the evolution patterns of kidney Yang deficiency syndrome in CKD. MethodThe evidence information of 256 patients with CKD was collected from October 2020 to September 2022 according to relevant standards, and the "Kidney Yang Deficiency Syndrome Evaluation Scale for Chronic Kidney Disease" was developed. With SPSS Statistics 20.0, SPSS Modeler 18.0, Gephi 0.9.2, and R 4.2.1, the syndrome information of CKD patients at various stages and the syndrome changes after one year were statistically analyzed using complex network analysis, association rule analysis, probability transition matrix analysis, and chi-square test, and the kidney Yang deficiency syndrome of patients at various stages was comprehensively evaluated. ResultIn the CKD population, the proportion of females with kidney Yang deficiency syndrome was higher than that of males (P<0.01), and the proportion of people over 65 years old was higher than in people under 65 years old. The proportion of people with kidney Yang deficiency syndrome increased with the progression of kidney disease, and the proportion of Ⅳ-Ⅴ CKD patients with kidney Yang deficiency syndrome was higher than that of Ⅰ-Ⅱ CKD patients (P<0.01). From Ⅰ CKD to Ⅴ CKD, the frequency of dull tongue continued to increase, and the frequency of enlarged tongue and tooth-marked tongue continued to increase after Ⅲ CKD. The frequency of thick coating and greasy coating ranked in the top 3 of frequency distribution in Ⅴ CKD. After Ⅲ CKD, the top 3 tongue characteristics were weak pulse, deep pulse, and thready pulse, all of which were characteristics of kidney Yang deficiency syndrome. Complex network analysis of the tongue and pulse showed that the core tongue and pulse characteristics of patients with end-stage CKD were tooth-marked tongue with white coating and deep and thready pulse. The results of symptom frequency analysis and complex network analysis showed that aversion to cold and preference for warmth, weakness of the knees, and cold extremities were the top 3 symptoms in Ⅰ-Ⅲ CKD patients with kidney Yang deficiency syndrome, and in Ⅳ-Ⅴ CKD, the manifestations of the syndrome of Yang deficiency and water diffusion, such as drowsiness and fatigue, edema, and frequent urination at night became characteristic symptoms. The scores of edema, pale complexion, soreness and weakness of the waist and knees, loose stools, and mental depression symptoms, as well as the total score of kidney Yang deficiency syndrome gradually increased with disease progression, with statistical differences between different stages of CKD (P<0.05, P<0.01). The frequency analysis of disease-related syndrome elements showed that the frequencies of Yang deficiency syndrome, phlegm-dampness syndrome, blood stasis syndrome, and turbidity-toxin syndrome gradually increased with disease progression, and there were statistically significant differences in the distribution between different stages of CKD (P<0.05, P<0.01). The results of complex network analysis showed that Yang deficiency syndrome was the core syndrome element throughout all stages of CKD and was the main syndrome element type of CKD, while phlegm-dampness syndrome, blood stasis syndrome, and turbidity-toxin syndrome were gradually revealed in the middle and late stages of CKD. In the CKD population with kidney-Yang deficiency syndrome, the distribution of phlegm-dampness syndrome, blood stasis syndrome, and turbidity-toxin syndrome as concurrent syndromes in different CKD stages had statistically significant differences (P<0.05, P<0.01). The association rule analysis showed that as the disease progressed, associations between the concurrent syndromes, such as phlegm-dampness syndrome, blood stasis syndrome, turbidity-toxin syndrome, and fluid retention syndrome, and kidney-Yang deficiency syndrome were gradually enhanced. The comparison of the changes in CKD with kidney Yang deficiency syndrome within one year showed that the disease location was centered on the kidney and transmitted between the spleen, stomach, heart, and liver. There is a 23.81% probability of kidney-Yang deficiency syndrome transforming into Qi deficiency syndromes (Qi deficiency in the spleen and kidney, Qi deficiency in the liver, and Qi deficiency in the heart), 23.79% into Yin deficiency syndromes (Yin deficiency in the liver and kidney, Qi and Yin deficiency, and Yin deficiency in the liver and stomach), and 9.52% into dampness syndromes (phlegm-dampness internal obstruction and wind-dampness obstruction). In contrast, 20% of spleen and kidney Qi deficiency syndrome transformed into kidney Yang deficiency syndrome, and 33.33% of Qi deficiency and blood stasis syndrome transformed into kidney Yang deficiency syndrome. ConclusionAs Ⅰ CKD progresses to Ⅴ CKD, the severity of kidney Yang deficiency syndrome gradually increases, and the syndrome characteristics of kidney Yang deficiency become pronounced. Furthermore, the pathogenic factors, such as phlegm-dampness, blood stasis, and turbidity-toxin, gradually increase. With the change of time, kidney Yang deficiency syndrome in CKD tends to evolve into syndromes related to Qi deficiency, Yin deficiency, and dampness. The discovery of these rules provides a theoretical basis and reference guidance for the treatment of CKD based on syndrome differentiation.

13.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 126-132, 2023.
Article in Chinese | WPRIM | ID: wpr-972294

ABSTRACT

ObjectiveTo observe the clinical effect of modified Jichuanjian on senile patients with slow transit constipation of spleen-kidney yang deficiency syndrome and the influence on brain-gut peptide. MethodA total of 150 senile patients with slow transit constipation were randomized into control group (75 cases) and observation group (75 cases) with the random number table method. The observation group was given modified Jichuanjian (oral, 1 dose/day, 4 weeks), and the control group was treated with Biantong Capsules (oral, 3 capsules/time, twice/day, 4 weeks). Data before and after treatment were recorded, including the score of major constipation symptoms, score of Patient Assessment of Constipation Quality of Life (PAC-QOL), TCM syndrome score, spontaneous complete bowel movements (SCBM), colonic transit test, serum 5-hydroxytryptamine (5-HT), 5-HT 4 receptor (5-HT4R), somatostatin (SS), and vasoactive intestinal peptide (VIP), and recurrence. ResultThe total effective rate of the observation group was 93.06% (67/72), as compared with the 74.65% (53/71) in the control group (χ2=8.974 6, P<0.01). After treatment, the scores of major constipation symptoms, scores of four dimensions of PAC-QOL, total score of PAC-QOL, and TCM syndrome score were lower than those before treatment in the two groups (P<0.01), and lower in the observation group than in the control group (P<0.01). The SCBM in the observation group were more than those in the control group at the 2nd, 3rd, 4th weeks after treatment (P<0.01). The proportions of residual markers at 24, 48, 72 h after treatment were smaller than those before treatment in the two groups (P<0.01), and smaller in the observation group than in the control group (P<0.01). After treatment, the levels of serum 5-HT and 5-HT4R were higher (P<0.01) and the levels of serum SS and VIP were lower (P<0.01) than those before treatment in the two groups. In addition, the levels of serum 5-HT and 5-HT4R in the observation group were higher (P<0.01) and the levels of serum SS and VIP were lower (P<0.01) in the observation group than in the control group. The recurrence in the observation group was 29.85% (20/67) in comparison with the 58.49% (31/53) in the control group (χ2=9.932 4, P<0.01). ConclusionModified Jichuanjian is effective for senile patients with slow transit constipation of spleen-kidney yang deficiency syndrome, which can alleviate clinical symptoms, improve quality of life, regulate the level of serum brain-gut peptide, improve the colonic transit function, increase SCBM, and reduce the recurrence.

14.
Chinese Journal of Practical Nursing ; (36): 166-171, 2022.
Article in Chinese | WPRIM | ID: wpr-930594

ABSTRACT

Objective:To observe the curative effect and temperature safety management of ginger mud moxibustion of different thickness on ankylosing spondylitis patients with kidney yang deficiency type, and to explore the best curative effect combination and safety combination of ginger mud thickness in Du Meridian moxibustion.Methods:From March 2020 to March 2021, 90 patients with ankylosing spondylitis of kidney yang deficiency type who were treated with Du moxibustion in the Affiliated Hospital of Nanjing University of Chinese Medicine were selected. According to the thickness of ginger paste, they were randomly divided into 2 cm-thick ginger mud thickness group, 3 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group when the diameter and height of moxa wool were the same as 2 cm, 30 cases in each group. They were treated with Fu Yang Du moxibustion once a week for 60 minutes each time. Visual Analogue Scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), traditional Chinese medicine syndrome score were used to evaluate the curative effect of spinal function before and after the intervention for 6 weeks. The time when moxibustion temperature reached 43 ℃ and moxibustion temperature maintained at 43-45 ℃ were analyzed for safety evaluation.Results:After moxibustion, VAS scores of 2 cm-thick ginger mud thickness group, 3 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group were 2.89 ± 0.96, 2.01 ± 0.69, 2.93 ± 1.23, BASDAI scores were 3.51 ± 0.94, 2.69 ± 0.68, 3.13 ± 0.96 and BASFI scores were 1.71 ± 0.99, 0.99 ± 0.36, 1.61 ± 0.50, the traditional Chinese medicine syndrome scores were 15.97 ± 4.61, 12.08 ± 3.21, 13.79 ± 3.58. The scores of the three groups were statistically significant ( F values were 6.51-19.22, all P<0.05) . After the intervention, there were significant differences in the scores between 2 cm-thick ginger mud thickness group and 3 cm-thick ginger mud thickness group, 2 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group, 3 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group ( t values were -6.61-4.56, all P<0.05). Conclusions:Du moxibustion is an effective method to treat ankylosing spondylitis of kidney yang deficiency type. The best curative effect and safety combination is moxa velvet diameter height 2 cm, ginger mud thickness 3 cm.

15.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 8-14, 2022.
Article in Chinese | WPRIM | ID: wpr-940790

ABSTRACT

ObjectiveTo observe the clinical effect of governor meridian moxibustion combined with modified Youguiwan in treating erectile dysfunction of kidney Yang deficiency type and its influence on the level of sex hormones and penile hemodynamics. MethodA total of 120 patients were randomized into the control group (60 cases in total, 3 dropouts/lost to follow-ups, 57 finally included) and treatment group (60 cases in total, 2 dropouts/lost to follow-ups, 58 finally included) with the random number table method. Both groups received governor meridian moxibustion (1 time/w, a total of 4 times). In addition, the control group took oral compound Xuanju capsule (3 capsules/time, 3 times/d), and the treatment group was given Jiawei Youguiwan (Chinese medicine decoction, 1 dose/d). The administration lasted 4 weeks for both groups. The scores of 5th edition international index of erectile function (IIEF-5), erection quality scale (EQS), and erectile hardness score (EHS), traditional Chinese medicine (TCM) syndrome score, levels of sex hormones [testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL)], and parameters of penile hemodynamics [peak systolic velocity (PSV), end-diastolic volume (EDV), and resistance index (RI)] were recorded. ResultAfter treatment, the total effective rate was 87.93% (51/58) in the treatment group, higher than the 71.93% (41/57) in the control group (χ2=4.600 3, P<0.05). After treatment, compared with before treatment,the treatment group registered increase in the scores of IIEF-5, EQS, and EHS (P<0.01), decrease in TCM syndrome score (P<0.01), rise of serum T level (P<0.05), reduction in the levels of FSH, LH, and PRL (P<0.05), increase in the levels of PSV and RI (P<0.05), and down-regulation of EDV level (P<0.05). ConclusionGovernor meridian moxibustion combined with modified Youguiwan can effectively improve the penile erectile function, erectile hardness, and erection quality, and relieve the clinical symptoms of erectile dysfunction patients of kidney Yang deficiency type.

16.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 204-213, 2022.
Article in Chinese | WPRIM | ID: wpr-940192

ABSTRACT

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.

17.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 128-138, 2022.
Article in Chinese | WPRIM | ID: wpr-940184

ABSTRACT

ObjectiveTo explain the scientific connotation of Morindae Officinalis Radix (MOR) processed by Glycyrrhizae Radix et Rhizoma (Gly) by comparing the effect of raw products of MOR and processed products of MOR with different proportions of Gly (GMOs) on the improvement of renal function and hypothalamic-pituitary-gonadal (HPG) axis, the protein expression of Wnt/β-catenin and transforming growth factor-β1 (TGF-β1)/Smad signal pathways in kidney Yang deficiency model rats induced by adenine. MethodGMOs were prepared according to method under MOR in 2020 edition of Chinese Pharmacopoeia. Rat model of kidney Yang deficiency was established by intragastrical administration of adenine, levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and testosterone (T) were measured by enzyme-linked immunosorbent assay (ELISA). Levels of urea nitrogen (BUN) and serum creatinine (SCr) were measured by spectrophotometry, hematoxylin-eosin (HE) staining was used to evaluate the pathological changes of kidney, testis and epididymis. Immunohistochemistry (IHC) was used to analyze the protein expression of E-cadherin, α-smooth muscle actin (α-SMA), Wnt2b, β-catenin, Smad1 and Smad4. ResultMOR processed with 100∶6 and 100∶12 proportions of Gly (short for GMO/100∶6 and GMO/100∶12) had the most obvious improvement on the body posture of kidney Yang deficiency model rats. GMO/100∶12 had the best effect on reducing the levels of BUN, SCr, FSH, LH and the ratio of E2/T. GMO/100∶6 and GMO/100∶12 had the best effect on regulating the protein expression of E-cadherin, α-SMA, Wnt2b, β-catenin, Smad1 and Smad4. ConclusionGMO/100∶6 and GMO/100∶12 have the a good effect on the improvement of renal function and HPG axis in kidney Yang deficiency model rats induced by adenine, which is related with the fact that they can regulate Wnt/β-catenin pathway in renal and testicular tissue and TGF-β1/Smads pathway in testicular tissue.

18.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 204-213, 2022.
Article in Chinese | WPRIM | ID: wpr-940160

ABSTRACT

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.

19.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 128-138, 2022.
Article in Chinese | WPRIM | ID: wpr-940152

ABSTRACT

ObjectiveTo explain the scientific connotation of Morindae Officinalis Radix (MOR) processed by Glycyrrhizae Radix et Rhizoma (Gly) by comparing the effect of raw products of MOR and processed products of MOR with different proportions of Gly (GMOs) on the improvement of renal function and hypothalamic-pituitary-gonadal (HPG) axis, the protein expression of Wnt/β-catenin and transforming growth factor-β1 (TGF-β1)/Smad signal pathways in kidney Yang deficiency model rats induced by adenine. MethodGMOs were prepared according to method under MOR in 2020 edition of Chinese Pharmacopoeia. Rat model of kidney Yang deficiency was established by intragastrical administration of adenine, levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and testosterone (T) were measured by enzyme-linked immunosorbent assay (ELISA). Levels of urea nitrogen (BUN) and serum creatinine (SCr) were measured by spectrophotometry, hematoxylin-eosin (HE) staining was used to evaluate the pathological changes of kidney, testis and epididymis. Immunohistochemistry (IHC) was used to analyze the protein expression of E-cadherin, α-smooth muscle actin (α-SMA), Wnt2b, β-catenin, Smad1 and Smad4. ResultMOR processed with 100∶6 and 100∶12 proportions of Gly (short for GMO/100∶6 and GMO/100∶12) had the most obvious improvement on the body posture of kidney Yang deficiency model rats. GMO/100∶12 had the best effect on reducing the levels of BUN, SCr, FSH, LH and the ratio of E2/T. GMO/100∶6 and GMO/100∶12 had the best effect on regulating the protein expression of E-cadherin, α-SMA, Wnt2b, β-catenin, Smad1 and Smad4. ConclusionGMO/100∶6 and GMO/100∶12 have the a good effect on the improvement of renal function and HPG axis in kidney Yang deficiency model rats induced by adenine, which is related with the fact that they can regulate Wnt/β-catenin pathway in renal and testicular tissue and TGF-β1/Smads pathway in testicular tissue.

20.
China Pharmacy ; (12): 1313-1319, 2022.
Article in Chinese | WPRIM | ID: wpr-924354

ABSTRACT

OBJECTIVE To explore the regulatory mechanism of compatibility of ginseng and gecko dispensing granule on kidney yang deficiency model rats. METHODS Male SD rats were randomly divided into normal group (no modeling ,no administration),model group (modeling,no administration ),Jinkui shenqi pill group (modeling,dose of 2.33 g/kg),ginseng group(modeling,dose of 0.53 g/kg),gecko group (modeling,dose of 0.21 g/kg)and compatibility group (modeling,ginseng 0.53 g/kg and gecko 0.21 g/kg). The body mass and anal temperature of rats were measured at different time points ;the serum levels of cAMP ,cGMP,CRH,ACTH,CORT,T,T3,T4,E2,IgG and IgM were measured ;the pathomorphological changes of adrenal gland ,thyroid gland and testis were observed ;mRNA expression of CRH ,thyroid stimulating hormone releasing hormone (TRH)and gonadotropin releasing hormone (GnRH)in hypothalamus were detected. RESULTS Compared with model group ,the anal temperature ,the levels of cAMP ,CRH,ACTH,CORT,T3,T and cAMP/cGMP ,T/E2 in serum and mRNA expressions of TRH and GnRH in hypothalamus were significantly increased in the compatibility group (P<0.05 or P<0.01);the levels of cGMP,E2 and IgG in serum and mRNA expression of CRH in hypothalamus decreased significantly (P<0.05 or P<0.01); the pathological injuries of adrenal gland ,thyroid gland and testis were all improved. Compared with ginseng or gecko dispensing granules alone ,the anal temperature and T/E 2 of rats in the compatibility group increased significantly ,and mRNA expression of CRH in hypothalamus decreasedsignificantly (P<0.05 or P<0.01). CONCLUSIONS Thecompatibility of ginseng and gecko dispensing granule has a synergistic regulatory effect on kidney yang deficiency model rats , the mechanism of which may be associated with hypothalamus-pituitary-adrenal axis , hypothalamus-pituitary-thyroid axis , hypothalamus-pituitary-gonad axis and neuroendocrine immune network formed by immune function. Compatible drugs are better than single drugs.

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