Meta-analysis Of Traditional Chinese Medicine In The Treatment Of Idiopathic Male Infertility And The Mechanism Of Effect Of Yishen Huoxue Decoction

Objective and Importance:The research objective was to study,analyze and propose workable treatment formula for Singapore children anorexia with Liver Stagnation and Spleen Deficiency.This research began with understanding the characteristics of Singapore children anorexia,its etiology and pathogenesis,followed by arriving at a proposal of treatment comprising prescriptions from the renowned Shang Han Lun(伤寒论)and TCM pediatric massage.The therapeutic principle was based on three levels of treatment principle in classical Shang Han Lun medical philosophy.These levels comprised firstly,treating human and its core composition instead of just treating the apparent illness and its symptoms.Secondly,applying and matching the right prescriptions to the corresponding syndromes.Thirdly,determining the root of illness and eradicate thoroughly.It was therefore proposed to cure children anorexia with Liver Stagnation and Spleen Deficiency by Spiriting the Liver and Sustaining the Spleen.In tandem with improvement in efficacy,this evidenced-based,standardized formula for diagnosis and treatment method would be suggested as a common guide to treat Singapore children anorexia with Liver Stagnation and Spleen Deficiency.With the successful result as a milestone,it is also the researcher’s wish to encourage further engagement in ShanghanLun’s theories and treatment methods for other medical projects and undertakings,with the goal of reducing patients’ long term medical burden.Research Methodology:This research began with questionnaires conducted for 450 children with anorexia.The purpose was to understand the causes,pathogenesis and different syndromes involved.The patients were mainly from Singapore ZhongHua TCM hospital and Jing Jing TCM clinic between September 2020 and April 2021.Statistical toolhad been applied to randomly assign 180 patients into group A,B and C of 60 patients each.Observation metrics consists of pediatric anorexia main and secondary symptoms as well as measurements relating to their quality of life.The treatment approach used was by spiriting the Liver’s stagnation and by sustaining the Spleen to rectify their deficiencies.Consequently,traditional Chinese medicine JianHe granules and TCM pediatric massage were applied either jointly or separately:Group A had been clinically assigned to be treated by JianHe granules and TCM pediatric massage jointly;Group B had been assigned to be treated solely with Chinese medicine-JianHe granules;Group C had been assigned to be treated purely by TCM pediatric massage.Network pharmacology had been applied to scientifically explain JianHe granules prescription composition rules,identify its core bioactive components and their effects to the human body and the disease.There was a 12 weeks of medical treatment period accompanied by another 6 weeks of post-treatment observation,covering a total of 18 weeks of research.The clinical research ended in October 2021.At the end of the research,the results were analyzed with statistical tools as well as Concept Lattice technique to arrive at conclusions pertaining Pathology and Quality of Life,two aspects of efficacy for the patients in question.Results:(1)Overall results suggested that A,B and C group had all achieved their respective efficacy upon completion of treatment course.(2)The Illness Healing efficacy at the end of 12 weeks of treatment showed that:Analyzing with the help of Kruskal-Wallis H test,the 3 methods attained statistical differences(P<0.01)in Illness efficacy,there had been significant improvement in Illness for all the 3 groups.As for the comparison between groups,uponBonferroni correction,there were statistical difference in treatment efficacy(P=0.030<0.05).Group A(combined use of JianHe granules and TCM pediatric massage)and group B(JianHe granules)statistically had no significant in efficacy(P=1.000>0.05).However,group A was statistically proven(P=0.043<0.05)to be more efficacious than group C(TCM pediatric massage).Group B and C had no statistical difference in efficacy(P=0.105<0.05).(3)The Illness Healing efficacy at the end of 18 weeks of treatment showed that:The 3 methods had significant statistical differences(P<0.01)in Illness efficacy,there had been prominent improvement for all the 3 groups.As for the efficacy comparison between groups,there was statistical difference(P=0.023<0.05)and differences were similar to those at the end of week 12.(4)The Syndrome Healing efficacy at every 2-week interval showed that:1)At Week 2:Wilcoxon’s Sign Rank Test showed that the 3 methods had statistical differences(P<0.01),there had been significant improvement in Syndrome efficacy for all the 3 groups.Kruskal-Wallis variance analysis showed no statistical difference for comparison between the groups(P=0.634>0.05).2)At Week 4:the 3 methods entirely had statistical differences(P=<0.01),there had been significant improvement in Syndrome efficacy for all the 3 groups.Variance analysis still showed no statistical difference for comparison between groups(P=0.131>0.05).3)At Week 6:the 3 methods entirely had statistical differences(P=<0.01),there had been an overall significant improvement in Syndrome efficacy for all the 3 groups.Variance analysis for between groups comparison,uponBonferroni correction,started to show significant statistical difference(P<0.01).4)At Week 12:at the end of treatment period,the 3 methods entirely had statistical differences(P<0.01),there had been an overall significant improvement in Syndrome efficacy for all the 3 groups.Variance analysis for between groups comparison showed significant statistical difference(P=0.006<0.01).Among them,group A and B statistically had no efficacy difference(P=1.000>0.05).Group A was statistically better than C(P=0.008<0.01),suggesting that group A’s Syndrome efficacy was significantly better than C.Group B was statistically better than group C(P=0.046<0.05),its Syndrome efficacy was more superior to C.5)At Week 18:at the end of the observation,the 3 methods entirely had statistical differences(P<0.01),there had been an overall significant improvement in Syndrome efficacy for all the 3 groups.Variance analysis for between groups comparison showed significant statistical difference(P=0.002<0.01).They yielded the same outcome as those at Week 12.6)Applying Concept Lattice to analyze Syndrome efficacy which suggested numbers of patients who had fully or distinctly recovered from syndrome effect,it was recorded that all 3 treatment methods had little efficacy at end of week 2.At the end of 18 week when the research clinical process was completed,group A achieved an overall efficacy rate of 53 cases out of 60 within group,representing 88%of the total patients.Group B scored 51 cases out of 60 within group,representing 85%of the total patients.Group C was the lowest,it had 38 cases out of 60,representing 63%of the group total.(5)The treatment efficacy of the 3 Main Symptoms for pediatric patients suffering from anorexia:1)At the end of 12 weeks of treatment period and another 6 weeks of observation period till week 18,results showed that the entire 3 groups have shown significant improvement in appetite,quantity of food intake and variety of food intake(P<0.01).2)Using Concept Lattice tool to analyze,when the full treatment course finished at week 18,group A had the best efficacy results.This group had 50 patients recovered from food quantity intake issue,48 recovered from food variety intake issue,and 39 recovered from appetite issue.Second best was group B,it had 43 patients recovered from food quantity intake issue,41 recovered from food variety intake issue,and 37 recovered from appetite problem.The last in ranking was group C,it had 35 patients recovered from food quantity intake issue,33 recovered from food variety intake issue,and 28 recovered from appetite issue.(6)The treatment efficacy of the twelve Secondary Symptoms for pediatric patients suffering from anorexia:1)At the end of 12 weeks of treatment period and another 6 weeks of observation period,the outcome had showed the entire 3 groups have exhibited significant improvement in the following Secondary Symptoms,namely,Weight,Facial Complexion,Spirit&Mood,Hypochondriac Distress,Irritation,Sleeping Disorder,Excitement,Stool,Tongue and Pulse symptoms(P<0.01).Except for the symptom of Bitterness&Sourness,Belching and Hiccupthat showed no improvement statistically(P>0.05).2)At the end of 12 weeks of treatment period and another 6 weeks of observation period,Variant analysis for comparison between groups showed that 4 symptoms,namely Facial Complexion,Hypochondriac Distress,Bitterness&Sourness and Stool recorded statistical differences(P<0.05).As for the other 8 secondary symptoms of Weight,Spirit&Mood,Belching&Hiccup,Irritation,Sleeping Disorder,Excitement,tongue and Pulse,comparison between groups showed no healing efficacy statistically(P>0.05).3)Concept Lattice tool reflected that when the full treatment course finished at week 18,group A again had the best efficacy results for the secondary symptoms with 40 patients returning to normal condition for 11 symptoms.They were Stool,Facial Complexion,Weight,Belching&Hiccup,Bitterness&Sourness,Spirit&Mood,Irritation,Sleeping disorder,Excitement,Hypochondriac Distress,and Pulse.Group B had 40 patients with 10 symptoms returning to normality.They were Stool,Irritation,Hypochondriac Distress,Excitement,Belching&Hiccup,Sleeping disorder,Facial Complexion,Bitterness&Sourness,Weight,and Pulse.Group C had 40 patients with just the symptoms of Belching&Hiccup and Stool returning to normal condition.Lattice analysis highlighted that group A and B treatment methods were effective for Stool,Belching&Hiccup,Irritation,Facial Complexion,Weight,Bitterness&Sourness,Excitement,Spirit&Mood,Hypochondriac Distress symptoms generally.Further to this,both group A and B have had more than 37 patients with completely 12 Secondary Symptoms returned to normality after 18 weeks,whereas only 30 patients in group C had achieved full symptom normality.Concept Lattice tool therefore reflected both group A and B performed better in Secondary Symptoms efficacy than C,both in terms of recovery time and number of patients recovered.(7)Quality of Life(QOL)assessment of overall efficacy:This research also took care of the well-being of patients by looking at the quality aspect of the patients.The QOL at the end of 12 weeks of treatment showed that group A had 28 patients(47%)achieved substantial improvement,another 21 patients(35%)achieved improvement,patients with ineffective results were 11(18%).It has an overall effective rate of 82%;Group B had 28 patients(47%)achieved substantial improvement,another 20 patients(33%)achieved improvement,ineffective numbers were 12(20%).It has an overall effective rate of 80%;Group C had 18 patients(30%)obtained substantial improvement,another 22 patients(37%)obtained improvement,ineffective numbers were 20(33%).The overall effective for the group was 67%.For comparison between groups,Kruskal-Wallis H statistical test showed thatthe 3 methods had statistical differences(P=0.049<0.05).Upon calibration by Bonferroni test,Group A and B statistically had no significant in QOL efficacy(P=1.000>0.05);Group A and C statistically had no significant in QOL efficacy(P=0.088>0.05);Group B and C statistically had no significant in QOL efficacy(P=0.113>0.05)The QOL at the end of 18th week showed that group A had 31 patients(52%)achieved substantial improvement,and another 28 patients(47%)attained improvement,ineffective QOL outcome was just 1 patient(2%).It has an overall effective rate of 98%;Group B had 30 patients(50%)achieved substantial improvement,and another 23 patients(38%)attained improvement,ineffective outcome was for 7 patients(12%).It has an overall effective rate of 88%;Group Chad 23 patients(38%)achieved substantial improvement,and another 27 patients(45%)attained improvement,ineffective outcome was for 10 patients(17).The overall effective for the group was 83%.Upon Kruskal-Wallis H statistical test,the 3 methods had no statistical differences(P=0.104>0.05)when comparing between groups.The reason being group C’s efficacy rate relatively improved faster than that of A and B during the observation period from week 12 to week 18,resulted in ending figures having no significance in statistical analysis.(8)Quality of Life(QOL)four main categories’assessment:The four main categories were Psychological,Cognitive,Physical and Social Relations functions.1)The psychological function was represented by Fear,Sad,Anger Uncontrollable and Sleeping Disorder,4 items of 60 patients each.Upon end of week 18 observation time,the efficacy rates for group A,B and C continued to improve(P<0.01).Between group comparison using generalized estimating equation(GEE)showed:statistical difference between Group A and B for Fear item;statistical difference between A and C for Sad item;the other items had no statistical significance in comparisons between pre and post treatment period.2)The Cognitive function was represented by Attention,Imitation and Expression,3 items of 60 patients each.At the end of week 18 observation time,the efficacy rates for group A,B and C continued to improve(P<0.01).As for between group comparison using GEE test,analysis showed that there was no statistical significancein treatment outcome among the 3 groups,except for Group A and B in Imitation item.3)The Physical function was represented by Bloat,Nausea,Liveliness and Hypersomnia,4 items of 60 patients each.At the end of week 18 observation time,the efficacy rates for group A,B and C continued to improve(P<0.01).As for between group comparison using GEE test,analysis showed that there was no statistical significancein treatment outcome among the 3 groups except for Nausea and Hypersomnia,Group A and C had statistical significance.4)The Social Relations function was represented by Participation,Eye contact,Avoidance,Smile,4 items of 60 patients each.Upon end of week 18 observation time,the efficacy rates for group A,B and C continued to improve(P<0.01).As for between group comparison using GEE test,analysis showed that there was no statistical significance in treatment outcome among the 3 groups except for Group A and C,all the 4 itemsof Participation,Eye contact,Avoidance,Smile had statistical significance.(9)Concept Lattice analysis of Quality of Life:The outcome of QOL applying Concept Lattice tool was in line with the illness efficacy outcome using statistical tools.This conclusion suggested that patients’ quality of life is closely linked to their physical health.(10)Applying network pharmacology to JianHegranules suggested that the analysis of this Chinese materia medica were scientifically consistent with their intended treatment effect.Conclusion and Significance:While Shaoyang and Taiyin channels were both dysfunctional thereby resultedchildren anorexia with Liver Stagnation and Spleen Deficiency,spiriting the Liver and sustaining the Spleen have proven both in medical healing efficacy and improvement in patients’quality of life in this research.Either treatment method of applying Chinese medicine JianHe granules or TCM pediatric massage could yield clinical efficacy and were safe to use.Their combined use achieved even better outcome.As this illness is common in Singapore,we would like to recommend their application for the patients.