Metabolic characteristics of Qi-Yin deficiency and heat stagnation in liver meridian patterns of dry eye based on tear metabolomics

Objective To explore the metabolic differences between dry eye patients with Qi-Yin defi-ciency and heat stagnation in liver meridian patterns,and clarify their metabolic characteris-tics.Methods Patients with dry eye who were treated in the Ophthalmology Ward and Outpatient Department of the First Hospital of Hunan University of Chinese Medicine from October 1,2020,to October 30,2021 were enrolled as the research participants in the study.They were assigned to two groups based on traditional Chinese medicine(TCM)syndrome types:heat stagnation in liver meridian pattern group and Qi-Yin deficiency pattern group.Healthy vol-unteers who underwent health check-ups in the Health Management Department were in-cluded as healthy group following the random number table method.The tears of the pa-tients and the healthy volunteer participants were tested by high-performance liquid chro-matography-mass spectrometry(LC-MS).The differential metabolites were screened out by multivariate statistical analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment was performed on the differential metabolites.Finally,the association analysis of differential proteins and metabolites was conducted to verify and supplement the metabolites.Results A total of 32 dry eye patients were enrolled,including 16 cases with heat stagnation in liver meridian pattern and 16 cases with Qi-Yin deficiency pattern.Fourteen healthy volun-teers were included as healthy group.There were no significant differences in baseline char-acteristics among the three groups(P>0.05).A total of 412 biomarkers were determined in Qi-Yin deficiency pattern group,mainly including lipids,lipid-like molecules,organic acids and their derivatives,organic heterocyclic compounds,and nucleosides and their analogues.For heat stagnation in liver meridian pattern group,112 metabolites were determined,main-ly including organic acids and their derivatives,lipids,and lipid-like molecules.The KEGG enrichment results of pathways and the relative content analysis of differential markers de-monstrate that purine metabolism and caffeine metabolism pathways are common metabol-ic characteristics of all dry eyes.Among them,deoxyinosine monophosphate(dIMP)and 2-(formamido)-N1-(5-phospha-D-ribosyl)acetamidine can serve as their biomarkers.The main characteristics of Qi-Yin deficiency syndrome pattern were the significant enhancement of metabolic pathways such as lysine degradation,ovarian steroidogenesis,cholesterol metabolism,pyrimidine metabolism,and bile secretion(P<0.05).Dry eye associated with the heat stagnation in liver meridian pattern is mainly characterized by inhibition of the valine,leucine,and isoleucine biosynthesis pathways(P<0.05).Conclusion Metabolomics can be used as an effective basis for TCM syndrome classification.Different patterns of dry eye syndrome exhibit typical characteristics in the types and concen-trations of metabolites,which correspond to the syndrome classification in TCM.This study initially confirms the rationality of TCM syndrome classification and provides significant ref-erence for the mechanism of dry eye and drug development.

Comparative evaluation in treating qi-yin deficiency and phlegm stasis syndrome of type 2 diabetes mellitus in a rat model

Objective:To compare the efficacy of traditional Chinese medicine (TCM),western medicine and integrative medicine in treating type 2 diabetes mellitus (T2DM) in a rat model.Methods:The T2DM rat model was established with a high-fat diet (HFD) for 35 days and a single injection of streptozotocin (STZ,30 mg/kg).The T2DM-induced rats were divided into three groups,and treated with Yiqi Yangyin Huatan (YQYYHT) granules (3.84 g/kg per day),pioglitazone (1.35 mg/kg per day) or YQYYHT granules + pioglitazone (3.84 g/kg per day+1.35 mg/kg per day) respectively for 14 days.Clinical features and behavioral changes,as well as T2DM indicators,were recorded to evaluate therapeutics effects in each treatment group.Results:The T2DM rat model expressed insulin resistance (IR),with features similar to qi-yin deficiency and phlegm stasis syndrome,including decreased cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio,decreased levels of Na+-K+-ATPase,superoxide dismutase (SOD) and high density lipoprotein-cholesterol (HDL-C),and increased levels of serum triglyceride (TG),total cholesterol (TC) and low density lipoprotein (LDL-C).All three treatment groups showed significant decreases in fasting blood glucose (FBG) and fasting insulin (Fins),and improvement of TCM syndrome to different degrees.Importantly,YQYYHT improved the most of the indicators of T2DM,followed by integrative medicine and pioglitazone alone.Conclusion:Compared with western medicine or integrative medicine,prescription of TCM based on syndrome differentiation may offer more advantages in the prevention and treatment of T2DM.

Efficacy of Yangyin Yiqi Huoxue Granule (养阴益气活血颗粒) in Treatment of Ischemic Stroke Patients with Qi-Yin Deficiency and Blood Stasis Syndrome: A Randomized, Double-Blind, Multicenter, Phase-2 Clinical Trial

Objective To evaluate the efficacy and safety of Yangyin Yiqi Huoxue Granule(养阴益气活血颗粒,YYHG)in the treatment of ischemic stroke(IS)patients with qi-yin deficiency and blood stasis syndrome(QYDBSS),and to explore its effective dosage.Methods The total of 288 patients were randomly assigned to the YYHG high-dose,YYHG low-dose,positive control(administered Xiaoshuantong Granule,XSTG,消栓通颗粒),or placebo control(administered inert granule)groups(72 cases per group)by software-drived competitive block randomization.The trial was conducted for a 28-day period,with a 180-day follow-up period.The primary outcome was the comprehensive curative evaluation,and secondary outcomes were the National Institute of Health Stroke Scale(NIHSS)score,Barthel activities of daily living(ADL)index score,the quality of life index(QLI)score,and the Chinese medicine syndrome(CMS)score.All analyses were done on an intention-to-treat basis.The clinical safety was also assessed.Results The total of 288 participants were recruited between June 1,2008 and September 30,2009,and 287 patients received intervention;the treatment groups were well balanced at baseline.The comprehensive cure rates of YYHG high-dose,low-dose,positive and placebo control groups were 63.38%,31.94%,36.11%and 6.14%,respectively;there was a statistical difference between the two groups(P<0.01),while the high-dose YYHG treatment group was significantly higher than the other 3 groups(P<0.01).The improvement of NIHSS,ADL,QLI and CMS scores of the YYHG high-dose and low-dose groups was significantly better than that of the positive control group and the placebo control group(P<0.05).In terms of improving the classification of the NIHSS scale and the assessment of the ADL scale,the YYHG high-dose group was significantly better than the other three groups(P<0.05),and the YYHG low-dose group was better than the placebo control group(P<0.01).At the same time,except for the QLI score,the high-dose group was better than the low-dose group(P<0.05).In terms of safety,adverse reactions after YYHG treatment were generally mild(3.78%),and no serious adverse reactions have been reported.Conclusion YYHG is safe and effective in the treatment of IS patients with QYDBSS.

Detwmination of Blood Flow in the Lower Leg of Patients withDiabetes Mellitus and the Effects of Treatment with thePrinciple of Vitalizing Blood and Solubilizing Thrombus

Blood flow in the lower leg was determined in 50 cases of non-insulin dependent diabetesmellitus using an XLJ-2 bipolar rheoencephalometry impedance rheogram. In patients with leg pain (85legsi and diabetic foat (15 legs3, the blood flow of the lower leg was decreased as compared withhealthy legs (P<0. 01￣0. 001) . The group with diabetic foot showed a bigger decrease compared withthe leg pain group (PMO. 051 . Atter treatment with the principle of vitalizing blood and solubilizing throm-bus, 22 cases with leg pain (32 legs) showed a significant increase of blood flow in the lower leg (P<0. 001). The group with diabetic foot failed to show any significant increase, indicating the importance ofearly treatment. This method of determining blood flow in the lower leg will help early discovery of abnor-mal changes of blood supply in the lower leg. Treatment with the principle of vitalizing blood and solubiliz-ing thrombus can help improve the conditions of the patients.