Meta-analysis Of Traditional Chinese Medicines For The Treatment Of BPH And Real-world Clinical Study Of Lingze Tablets For The Treatment Of BP

Benign prostatic hyperplasia(BPH)is a histological diagnosis of hyperplasia of smooth muscle and epithelial cells in the transition zone of the prostate.The number of patients increases with age and the symptoms are more common.Western medicine treatment has certain limitations.Patients with mild symptoms or moderate to severe disease mostly choose to watch and wait;drug treatment still has many adverse reactions,and there are many side effects;although the methods of surgery are diversified,its cost,safety and patient acceptance need to be further improved.Traditional Chinese medicine has significant advantages in the treatment of benign prostatic hyperplasia,which can effectively make up for the deficiency of western medicine in the treatment of this disease.Preliminary clinical trials have confirmed that Lingze tablets have certain advantages in the treatment of benign prostatic hyperplasia with kidney deficiency,blood stasis and dampness obstruction,and have obvious advantages in improving the International Prostate Symptom Score(IPSS),and have fewer adverse reactions.Based on the meta-analysis of Chinese patent medicine in the treatment of benign prostatic hyperplasia and the mechanism of action of Lingze tablets in the treatment of benign prostatic hyperplasia based on network pharmacology and molecular docking,the real-world clinical application of Lingze tablets in the treatment of benign prostatic hyperplasia will be carried out.Observation of the curative effect of traditional Chinese medicine in order to provide better ideas for the treatment of benign prostatic hyperplasia with Chinese patent medicine.Research 1:Meta-analysis of Chinese patent medicine in the treatment of benign prostatic hyperplasiaObjective:To objectively evaluate the clinical related indexes of Chinese patent medicine in the treatment of benign prostatic hyperplasia by means of Meta analysis,and to provide an objective basis for the clinical application of Chinese patent medicine in the treatment of benign prostatic hyperplasia.Methods:The databases of China National Academic Journals Full-text Database(CNKI),Chinese Scientific and Technological Periodicals Full-text Database(VIP),Wanfang Database,PUBMED,Cochrane and SCI were searched.In Chinese,the search terms are"benign prostatic hyperplasia" or "prostatic hyperplasia" or "benign prostatic hypertrophy" or"prostatic hypertrophy" or "BPH" and "Chinese patent medicine";in English,"Lower urinary tract syndrome","Luts","Benign prostatic hyperplasia","BPH","Chinese patent medicine"are search terms.The dates are set to run from January 2010 to March 2022.Relevant clinical literature studies were screened.In addition,to prevent missed detections,we performed an additional review of the references of the corresponding articles.Two people performed backto-back screening,data extraction,quality assessment,and data analysis of the retrieved articles according to the inclusion and exclusion criteria,respectively.Results:Meta-analysis of the 14 included papers found that:1.The effect of Chinese patent medicine treatment on IPSS score:the experimental group was significantly better than the control group in reducing IPSS score,the difference was statistically significant(WMD=-1.48,95%CI[-2.46,-0.50],Z=2.95(P<0.01);2.The effect of Chinese patent medicine treatment of BPH on QOL score:the experimental group was significantly better than the control group in reducing QOL score,with statistical significance(WMD=-0.44,95%CI[-0.55,-0.34],Z=8.33(P<0.01);3.The effect of Chinese patent medicine treatment on the maximum urine flow rate:the experimental group was significantly better than the control group in improving the maximum urine flow rate,the difference was statistically significant(WMD=1.38,95%CI[0.90,1.87],Z=5.59(P<0.01);4.Effect of Chinese patent medicine treatment on bladder residual urine volume:the experimental group was significantly better than the control group in improving bladder residual urine volume,the difference was statistically significant(WMD=-3.97,95%CI[-7.66,-0.28],Z=2.11(P<0.05);5.The effect of Chinese patent medicine treatment on prostate volume:there was no statistical significance in improving prostate volume in the experimental group compared with the control group(WMD=-0.43,95%CI[-1.70,0.87],Z=0.64(P>0.05);6.Efficacy analysis of Chinese patent medicine in the treatment of BPH:the experimental group was significantly better than the control group in clinical efficacy,and the difference was statistically significant(OR=0.11,95%CI[0.07,0.15],Z=5.12,P<0.01).Conclusion:Chinese patent medicine has obvious advantages in treating benign prostatic hyperplasia.Compared with the control group,it had significant advantages in effective rate,IPSS score,QOL score,maximum urine flow rate and residual urine volume of bladder.Compared with the control group,there was no statistical difference in the reduction of prostate volume in the treatment of BPH,and no significant effect was shown.Proprietary Chinese medicines have advantages in the treatment of benign prostatic hyperplasia in terms of adverse reactions.In the clinical use process,occasionally a small number of patients have some mild digestive symptoms,and no allergic reaction,liver and kidney function damage and other serious adverse reactions occur,which is of high safety and worthy of clinical promotion.Research 2:Based on network pharmacology and molecular docking,the mechanism of action of Lingze tablets in the treatment of benign prostatic hyperplasia was revealedObjective:To investigate the bioactive components and potential mechanism of Lingze tablets in the treatment of benign prostatic hyperplasia.Methods:Based on oral bioavailability and drug similarity,the main active components of Lingze tablets were screened using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP).GeneCard,OMIM,DisGeNET,DrugBank,PharmGkb,and Therapeutic Target Database were used to create a target database for benign prostatic hyperplasia.The "active ingredient-target-disease" visual interactive network diagram was constructed by Cytoscape software.The STRING database was used to construct a protein interaction network and analyze the interaction relationship of related proteins.The Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway and Gene Ontology(GO)biological process enrichment analysis were performed on the core targets.Molecular docking validation of active pharmaceutical ingredients and disease targets using Discovery Studio software.Results:23 active ingredients of Lingze tablets were screened,including 506 common targets.The benign prostatic hyperplasia targets obtained from the database were summarized,and the duplicates were deleted,and a total of 914 targets were obtained.After the intersection of compound drug targets and disease targets,a total of 146 intersection target genes were obtained.The results of network analysis showed that the predicted effects of Lingze tablets components on Proteoglycans in cancer signaling pathway,AGE-RAGE in diabetic complications signaling pathway,Focal adhesion signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,Calcium signaling pathway,Hepatitis B signaling pathway,Apoptosis signaling pathway,and Toxoplasmosis signaling pathway play a therapeutic role.Molecular docking results showed that the core active ingredients of Lingze tablets,7-Nitroindazole,Guanosine 3’,5’-cyclic,and Sildenafil,had good affinity and binding activity with key targets TNF,AKT1,and CASP3.Conclusion:Lingze tablets have the characteristics of multi-system,multi-component and multi-target in the treatment of benign prostatic hyperplasia.Its possible mechanisms of action include inhibiting tumor growth,inhibiting inflammation,regulating apoptosis,and reducing oxidative stress to control the occurrence and development of diseases.Research 3:Observation of curative effect of real-world clinical application of Lingze tablets in the treatment of benign prostatic hyperplasiaObjective:To observe the clinical efficacy and safety of Lingze tablets in the treatment of benign prostatic hyperplasia(BPH)in the real world.Methods:Selected 603 patients with benign prostatic hyperplasia who went to Beijing University of Traditional Chinese Medicine Dongzhimen Hospital and other hospitals from June 2019 to March 2020.The patients with benign prostatic hyperplasia included in the study were treated with Lingze tablets,and at the same time they were not treated.Intervention patients were taking other BPH-related drugs,and the International Prostate Symptom Score(IPSS),patient quality of life score(QOL)before and during treatment(day 30,60,and 90),and patients before treatment were observed.The nocturia frequency and urine flow rate after 90 days of treatment were compared with those before treatment,and the clinical efficacy of Lingze tablets in the treatment of benign prostatic hyperplasia was evaluated according to the observation indicators.Results:Compared with before treatment,the IPSS scores of each group decreased significantly after 30,60 and 90 days of treatment after Lingze tablets alone and in combination,and the difference was statistically significant(P<0.01).After 90 days of treatment,the QoL scores of each group decreased to varying degrees,and the difference was statistically significant(P<0.01).The maximum urine flow rate in each group was significantly increased after days,and the difference was statistically significant(P<0.01).No serious adverse reactions were found in all patients.Conclusion:The real-world study found that Lingze tablets are safe and effective in the treatment of benign prostatic hyperplasia,and can effectively reduce the IPSS score and QOL score of BPH patients,reduce the number of nocturia,increase the urinary flow rate,and improve prostate symptoms and patients’ quality of life.In the treatment of benign prostatic hyperplasia,Lingze tablets are worthy of clinical promotion.To sum up,this paper conducted network pharmacology and molecular docking for Lingze tablets in the treatment of BPH on the premise that the meta-analysis found that Proprietary Chinese medicines were safe and effective in the treatment of BPH and Lingze tablets had outstanding efficacy in the treatment of BPH.On the basis of the prediction results,further observation of the clinical application in the real world was carried out,and it was found that Lingze tablets had significant curative effect in the treatment-of patients with benign prostatic hyperplasia with syndrome of kidney deficiency and blood stasis and dampness obstruction,which is worthy of clinical promotion.