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

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

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

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

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

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

Serum Levels of Interleukin-1 Beta, Interleukin-6 and Melatonin over Summer and Winter in Kidney Deficiency Syndrome in Bizheng Rats

Objective To observe the seasonal changes in serum levels of interleukin-1 beta(IL-1β), interleukin-6(IL-6) and melatonin(MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis. Methods One hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer(n=80) and winter(n=80) respectively: normal group, collagen-induced arthritis(CIA) model group, operation group, and sham-operation group(n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was. The serum levels of IL-1β, IL-6 and MT in different groups were measured by radioimmunoassay. Results Compared with the normal group, the serum levels of IL-1β and IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter(IL-1β in summer, P=0.008, P<0.01, P=0.012; IL-1β in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024; IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1β and IL-6 in winter were higher than in summer, but with no statistically significant differences(P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group(P=0.002, 0.008) and the sham-operation group(P=0.003, 0.007), while significantly decreased in the operation group(P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter(P=0.947). Conclusions The increase of serum levels of IL-1β and IL-6 may exacerbate the inflammatoryreaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1β, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.

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

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

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

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

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

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

Preventive online and offline health management intervention in polycystic ovary syndrome

BACKGROUND Polycystic ovary syndrome(PCOS) is characterized by hyperandrogenism, hyperinsulinemia, ovarian polycystic changes, and irregular ovulation, often occurring in women of childbearing age for whom it can be a cause of infertility. Hypothalamus-pituitary-ovarian axis dysregulation is important in the pathogenesis of PCOS and the associated chronic excess of sex hormones can lead to cardiovascular and cerebrovascular diseases, diabetes, and malignancies such as endometrial cancer, and breast cancer. At present, most scholars agree that lifestyle interventions in conjunction with drug treatment can help PCOS patients achieve their goals of successful pregnancy and childbirth.AIM To investigate the clinical effect of an online and offline(O2O) preventive health management model on PCOS with kidney deficiency and phlegm dampness.METHODS A total of 82 patients with PCOS of the kidney deficiency and phlegm dampness type who were admitted to Beijing Luhe Hospital Affiliated to Capital Medical University from April 2019 to June 2020 were randomly divided into two groups. The treatment group was treated with oral Diane-35 for 3 mo and received preventive O2O medical health management for 6 mo(including eating and living, exercise, drug management). The control group was treated with oral Diane-35 for 3 mo and completed outpatient health education. The traditional Chinese medicine(TCM) syndrome score, acne score, hair score, sex hormone level and clinical effects were compared between the two groups before and after the intervention. RESULTS After treatment, the TCM syndrome score, acne score, and serum luteinizing hormone/follicle stimulating hormone level were significantly lower in the treatment group than in the control group(P < 0.05). After 3 mo of treatment, the TCM syndrome curative effect index in the treatment group was 97.30% compared to 54.05% in the control group(P < 0.05), whereas the total treatment effect in the treatment group was 91.89%, compared to 54.05% in the control group(P < 0.05).CONCLUSION An integrated therapeutic approach incorporating medication, TCM methods and social media is more effective than standard treatment for PCOS.

Clinical treatment of myasthenia gravis with deficiency of spleen and kidney based on combination of disease with syndrome theory

OBJECTIVE: To study the use of Jianjining in the treatment of myasthenia gravis (MG) patients with a deficiency of both spleen and kidney via the theory on the combination of disease with syndrome. METHODS: Sixty MG patients with a deficiency of both spleen and kidney were randomly divided into an treatment group (n=30) treated with Jianjining granules and Western Medicine (prednisone or pyridostigmine bromide) and a control group (n= 30) treated with Jianjining granules. The dosage of the three drugs was reduced over the course of treatment. After 3 and 6 months of treatment, the curative effect was evaluated with the muscle weakness severity scale (MWSS). RESULTS: The MWSS score after treatment declined significantly in both groups. The score in the treatment group was much lower than that in thecontrol group (P<0.05). The total effective rate was 63.33% (19/30) in the treatment group and 36.67% (11/30) in the control group after 3 months of treatment, and 80.00% (24/30) and 50.00% (15/30), respectively, after 6 months of treatment. The obvious and total effective rates in the treatment group were much higher than those in the control group (P<0.05). After 6 months of treatment, there were no obvious differences (P>0.05) in the obvious and effective rates between the 2 groups. However, the total effective rate in the treatment group was much higher than that in the control group (P<0.01). CONCLUSION: Using the theory on the combination of disease with syndrome, we found that the curative effect of Jianjining and Western Medicine on MG patients with deficiency of both spleen and kidney is worth further exploration.

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

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

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

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

Shen(Kidney)-Tonifying Principle for Primary Osteoporosis:to Treat Both the Disease and the Chinese Medicine Syndrome

Primary osteoporosis （POP） is one of the most common diseases in the elderly people resulting in high risk of fracture and poor quality of life. In addition to the pathological changes in bone mass, most of the POP patients also suffer from Chinese medicine （CM） syndromes of Shen （Kidney） essence deficiency. Shen essences are highly related to bone. Shen essence deficiency plays an important part in the development of POP and a better diagnosis of POP could be made by combining CM syndromes with Western medicine risk factors. Treatments of POP should aim at both increasing the bone mass and relieving the syndromes of Shen essence deficiency. Clinical study confirmed that treating POP patients with Shen-tonifying herbs could increase the bone mass and relieve the CM syndromes of POP patients. Basic researches clarified the mechanism by which Shen-tonifying herbs increased bone mass in animal models. The mechanisms by which Shentonifying herbs relieve the CM syndromes are still in investigation.

Study on Molecular Mechanism of Liver Yang Ascending Syndrome in Hypertension

Objective: To investigate the molecular mechanism of Liver Yang Ascending Syndrome (LYAS) in hypertension. Methods: The plasma norepinephrine (NE), epinephrine (E) contents in patients with LYAS or Liver and Kidney Yin Deficiency Syndrome (LKYDS) of hypertension and normal controls were determined by high performance liquid chromatography-electrochemical detector (HPLC-ECD). The polymorphism of tyrosine hydroxylase (TH) gene in the three groups were analysed by Southern Blot assay. The polymorphism of TH and monoamine oxidation A(MAO-A), monoamine oxidation B(MAO-B) gene microsatellite in these groups were analysed by polymerase chain reaction (PCR)-SSCP. At the same time, the LYAS model was established by administering Aconitum preparation (AP) to spontaneous hypertension rats (SHR). The adrenal gland medulla of the experimental animal was examined for their TH expression at the protein level after ABC immuno-histochemical staining with the TH monoclonal antibody (McAb). The adrenal TH gene mRNA expression was demonstrated by in situ hybridization with the synthetized TH oligonucleic acid probe. The results of immuno-histochemistry and in situ hybridization were analyzed with the image analysis system (IAS). Results: The plasma NE and E contents in patients with LYAS were more obviously increased than those in LKYDS and normal controls. The TH gene amplified and the type A1 TH microsatellite D11S4046 was markedly higher in the LYAS group than those in the other groups. The TH mRNA protein expression in the adrenal tissue of the AP induced LYAS model in SHR elevated. Conclusion: The LYAS of hypertension has the characters as amplified TH gene and increased TH mRNA and protein expression, which suggested that the overexpression of TH is probably the mechanism of LYAS in hypertension.

长蛇灸对肾阳虚大鼠HPA轴及肝脏11β-HSD1的影响

Objective:To observe the effects of long-snake moxibustion on the hypothalamic-pituitary-adrenocortical(HPA)axis and hepatic 11β-hydroxy steroid dehydrogenase type 1(11β-HSD1)expression in rats with kidney yang deficiency to provide a basis for later in-depth exploration of the action mechanism of longsnakemoxibustion on suchrats.Methods:Fifteen SPF-grade,male,SD rats were randomly divided into a blank control group,a model group,and a long-snake moxibustion treatment group,with five rats in each group.Hydrocortisone powder(30 mg/kg)was administered by gavage at a volume of 10 mL/kg to prepare the rat model of kidney yang deficiency.After successful modeling,the rats in the long-snake moxibustion treatment group underwent long-snake moxibustion treatment every other day along the governor vessel from Dazhui(GV14)to Shenshu(BL23),for a period of 14 days.The remaining two groups were secured in the same way as the long-snake moxibustion treatment group,although they did not receive any treatment.The body weight,rectal temperature,and spontaneous activity count of the rats,as well as serum levels of corticotropin releasing hormone(CRH)and corticosterone(CORT)were detected by ELISA before modeling,after modeling,and after treatment.The amount of 11β-HSD1 protein in rat liver was determined by immunohistochemistry and Western blot analysis.Results:Compared with the rats in the blank control group,those in the model group exhibited a significant decrease in the trend of body weight growth and in rectal temperature(P<0.05),as well as a slight yet non-significant decrease in spontaneous activity count(P>0.05);compared with the rats in the model group,the rats in the treatment group exhibited a significant increase in rectal temperature(P<0.05)and in spontaneous activity count(P<0.05).Moreover,after 14 days of treatment,compared with the rats in the blank,the rats in the model group exhibited a significant decrease in serum cORT content(P<0.05)and in the expression of 11β-HSD1 in the liver(P<0.05),as well as a slight yet non-significant decrease in serum CRH content(P>0.05);compared with the rats in the model group,the rats in the treatment group exhibited a significant increase in serum CRH content(P<0.05)and in the expression of 11β-HSD1 in the liver(P<0.05),as well as a slight yet non-significant increase in serum CORT content(P>0.05).Conclusion:Long-snake moxibustion can increase the rectal temperature and spontaneous activity count of rats with kidney yang deficiency,improve the function of the HPA axis,and increase the expression of 11β-HSD1 in the liver.

Efficacy and Safety of Guilingji Capsules(龟龄集胶囊)for Treating Mild-to-Moderate Cognitive Impairment:Study Protocol for A Randomized,Double-Blind,Positive-Controlled,Multicenter and Noninferiority Trial

Background:The incidence of cognitive impairment(CI)is gradually increasing,which has attracted more attention from medical researchers worldwide.Definitive mechanisms of pathogenesis remain elusive,and there are few medications that have been proven effective for CI.The utilization of Chinese herbal medicine has shown positive therapeutic effects for a broad spectrum of diseases,including CI.Objective:The purpose of this study is to evaluate the safety and efficacy of Guilingji Capsules(GLJC,龟龄集胶囊)in treating mild-to-moderate CI with Shen(Kidney)and marrow deficiency syndrome.Methods:This is a randomized,double-blind,positive-controlled,multicenter clinical trial with a noninferiority design that included 348 participants randomly divided into an experimental arm and an active comparator arm.Individuals in the experimental arm(174 cases)took 0.6 g of GLJC once a day and 19.2 mg of Gingko biloba extract mimetic 3 times a day.Individuals in the active comparator arm(174 cases)took 0.6 g of GLJC mimetic once a day and 19.2 mg of Gingko biloba extract in tablet form 3 times a day.The intervention period included two sessions over 24 weeks.The primary outcome be the effectiveness of GLJC on cognitive improvement after 24 weeks of treatment,which was defined as an increase in the Mini Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA)Scale.The secondary outcomes were improvement in independence,daily living ability,and Chinese medicine(CM)syndrome,which were measured with the Alzheimer’s disease Rating Scale-Cognitive Project(ADAS-Cog),Clinical Dementia Rating(CDR)Total Score,Activities of Daily Living(ADL)Total Score and the Chinese Medicine Symptom Scale(CM-SS),respectively.Serum acetylcholine,acetylcholinesterase,bax and bcl-2 were monitored to explore the mechanism of GLJC on CI.In addition,safety measures,including vital signs,electrocardiography,laboratory indicators(full blood count,kidney and liver function tests,routine urine test and routine stool test)and adverse events,were also recorded.Discussion:The purpose of this trial is to evaluate the efficacy and safety of GLJC in patients with mild-to-moderate CI with kidney and marrow deficiency syndrome.If successful,the results would provide a viable treatment for patients with mild-to-moderate CI.