Meta-analysis of Tonifying-Kindney and Soothing-Liver traditional Chinese medicine method in the treatment of polycystic ovary syndrome

Background:To systematically evaluate the clinical efficacy of Tonifying-Kindney and Soothing-Liver method in the treatment of polycystic ovary syndrome(PCOS).Methods:The literatures of randomized controlled trials(RCTs)on the treatment of PCOS with traditional Chinese medicine(TCM)published at home and abroad until March 2020 were retrieved,and RCTs on the treatment of PCOS with Tonifying-Kindney and Soothing-Liver method were collected.According to the systematic evaluation method of the Cochrane Collaboration Network,RevMan5.3 software was used to perform quality evaluation and data extraction for meta-analysis of tests that met the inclusion criteria.Results:A total of 30 eligible RCTs were included,including 2244 patients.Meta-analysis results show that the method of tonifying the kidney and Soothing-Liver has certain advantages in the treatment of PCOS.Compared with Western medicine alone group,tonifying the kidney and Soothing-Liver TCM method alone or combined with Western medicine could improve the total effective rate[OR=3.52,95%CI(2.67,4.63),I2=0%,P<0.00001].It is superior to the control group in improving ovulation rate[OR=2.01,95%CI(1.46,2.78),I2=0%,P<0.0001],pregnancy rate[OR=2.82,95%CI(2.28,3.49),I2=0%,P<0.00001],reducing LH[MD=-2.65,95%CI(-3.43,-1.88),I2=92%,P<0.00001]and ovarian stimulating hormone levels[MD=-0.52,95%CI(-0.85,-0.18),I2=94%,P=0.002].There was no statistical difference in reducing serum testosterone levels[SMD=-0.56,95%CI(-1.22,0.09),I2=96%,P=0.09]and improving TCM symptoms[MD=-0.09,95%CI(-4.75,4.56),I2=97%,P=0.97].Conclusion:The method of tonifying the kidney and Soothing-Liver has a certain effect in treating polycystic ovary syndrome,but the evidence is still very limited,and a large sample of high-quality randomized controlled studies is still needed in order to make a more rigorous evaluation.

The Diagnostic Criteria of Blood-Stasis Syndrome:Considerations for Standardization of Pattern Identification

Pattern identification （PI）, also called Bian Zheng （辨证）, syndrome differentiation, pattem diagnosis, or pattem classification, is the basic principle and the key concept of Chinese medicine （CM）. The core of PI is CM syndrome, on which CM theory, therapeutic method, prescribing formula and the use of Chinese herbal medicine are basically based. PI, in fact, is another classification method anticipated to improve the clinical efficacy. How to make an exact PI seems to be very important for taking full advantage of PI in clinical practice. Therefore, the establishment of diagnostic criterion of pattern has been the prerequisite for the standardization of PI. In recent years, a lot of diagnostic criteria of different CM patterns have been formulated. Taking the diagnostic criteria for blood-stasis syndrome as a model, the methodologies and considerations in establishing a pattern diagnostic criterion were discussed in this paper, which might be of great reference value in future PI standardization research.

Expression of T-Helper 17 Cells and Signal Transducers in Patients with Psoriasis Vulgaris of Blood-Heat Syndrome and Blood-Stasis Syndrome

Objective： To investigate the levels of cytokines related to T-helper （Th） 17 cells in serum and signal transducers in the psoriatic lesions of patients with psoriasis vulgaris of blood-heat syndrome （BHS） and blood-stasis syndrome （BSS）. Methods： Sixty patients with psoriasis vulgaris were divided into the BHS and BSS groups according to the syndrome differentiation of Chinese medicine （CM）. Ten healthy subjects were considered as the control group. Cytokine levels of interleukin （IL）-17, IL-23 and IL-6 in serum were determined by enzyme-linked immunosorbent assay. Expression levels of signal transducer and activator of transcription 3 （STAT3）, p38-mitogen-activated protein kinase （MAPK） and STAT6 in the psoriatic lesions were determined using immunohistochemistry （IHC）, Western blot, and real-time quantitative reverse transcription polymerase chain reaction, respectively. Results： Production of IL-17, IL-23 and IL-6 in the BHS group and BSS group were significantly increased compared with those in the control group （P〈0.05）. Levels of IL-17 and IL-23 in the BHS group were higher than those in the BSS group （P〈0.05）. Compared with the control group, IHC positive expressions and protein expressions of STAT3 and p38-MAPK, and the STAT3 mRNA expressions in the BHS and BSS groups were significantly higher （P〈0.05 or P〈0.01）. The protein expression of STAT3 in the BHS group was significantly higher than that in the BSS group （P〈0.05）. Conclusions： Cytokines in serum and signal transducers in the psoriatic lesions alter with various CM syndromes of psoriasis. The results provide scientific basis for the treatment based on syndrome differentiation of CM in treating psoriasis vulgaris.

Relationship between Platelet Activation Related Factors and Polymorphism of Related Genes in Patients with Coronary Heart Disease of Blood-stasis Syndrome

Objective： To comparatively study the expressive conditions of platelet activation related factors （GPⅠb, GPⅡb-Ⅲa and GMP-140） in healthy subjects and patients with coronary heart disease （CHD） of blood-stasis （BS） or non-blood-stasis （non-BS） syndrome, and to analyze the relationship between the activities of various glycoproteins and the polymorphism of genes. Methods： With case control design adopted, patients with the CHD （40 of BS, 37 of non-BS） and 39 healthy subjects for control, all fitting to the inclusion criteria, were selected in this study. The number of affected coronary branches was recorded by the contrast examination. The mean fluorescence intensity （MFI） of GPⅠb, GPⅡb-Ⅲa, and GMP-140 （CD42b, CD61, CD62p） in patients and healthy persons was measured with flow cytometry, the polymorphism of HPA-3 gene was detected by Taqman probe technique and that of HPA-2 gene was determined by gene sequencing. Results： MFI of CD61 and CD62p was higher in the CHD patients than in the healthy control, which was also higher in patients of BS syndrome than in patients of non-BS syndrome （P〈0.05）; MFI of CD42b was lower in the CHD patients than in the healthy control （P〈0.05）, but showing insignificant difference between BS and non-BS syndrome （P〉0.05）; at the same time, no significant difference of all the above-mentioned three MFI could be found in patients with various numbers of affected coronary branches, neither in patients with different genotypes at GPⅡb HPA-3 and GPⅠb HPA-2 polymorphism loci （P〉0.05）. Conclusion： （1） The activities of GP Ⅱ b-Ⅲa and GMP-140 were obviously increased in the genesis and developing process of CHD and CHD of BS syndrome, and so they could be taken as one of the objective indexes for microscopic diagnosis of BS syndrome. （2） The level of GPⅠb was lower in CHD patients than in healthy persons, but it was not a sensitive indicator for BS syndrome of CHD. （3） Levels of GP Ⅱb-Ⅲa, GPⅠb and GMP-140 were not related with the number of affected coronary branches in CHD patients. （4） The changes in amino-acids expression induced by the two loci brought no significant influence on GPⅠb and GP Ⅱb-Ⅲa activities.

Differential Expression of MicroRNA in Endothelial Cells Incubated with Serum of Hypertension Patients with Blood-Stasis Syndrome

Objective： To screen out blood-stasis syndrome （BSS）-associated microRNA and therefore determine the possible target for treating hypertension. Methods： A high-energy sequencing method and digital gene expression sequencing theory were adopted to sequence microRNA （miRNA） and messenger RNA （mRNA）, and to determine differential expression in human umbilical vein endothelial cells incubated with serum samples from hypertension patients with or without BSS, and healthy controls. The results were confirmed using gene prediction software. Results： A total of 13 miRNAs and 11 mRNAs showed statistical difference both in the BSS/normal groups and BSS/non-BSS groups, respectively. Four pairs of target mRNNmiRNA were identified： FRMD4Nhsa-miR-34a, MAP3K14/hsa-miR-34a, PER1/hsa-miR-34a, and FGF2/hsa-miR-132. Conclusion： Four mRNNmiRNA pairs mentioned above seem to be involved in pathogenesis and maintenance of hypertension with BSS.

Circulating Levels of Inflammatory Cytokines in Patients with Psoriasis Vulgaris of Different Chinese Medicine Syndromes

Objective： To investigate whether the serum levels of inflammation-related cytokines might be different between the healthy individuals and the psoriatic patients diagnosed of three varied Chinese medicine （CM） syndromes [blood-stasis syndrome （BSS）, blood-dryness syndrome （BDS） and wind-heat syndrome （WHS）]. Methods： A total of 62 psoriatic patients were recruited and assigned to 3 groups according to their CM syndromes, including 27 patients of BSS, 21 of BDS and 14 of WHS. Another 20 sex- and age- matched healthy subjects were enrolled into the control group. Serum concentrations of multiple cytokines, including monocyte chemotactic protein-1 （MCP-1）, macrophage inflammatory protein-1α （MIP-1α）, soluble CD40 ligand （SCD40L）, tumor necrosis factor-α （TNF-α）, epidermal growth factor （EGF）, interleukin-8 （IL-8）, interleukin-17 （IL-17）, interferon γ inducible protein-10 （IP-10） and vascular endothelial growth factor （VEGF）, were measured by a multiplexed flow cytometric assay. Results： The circulating levels of MIP-1α, TNF-α, IL-8, and IP-10 were significantly increased in the psoriatic patients compared with the healthy controls （P〈0.01）. Male and female patients tended to have higher serum levels of MCP-1 and IP-10, respectively （P〈0.05）. Interestingly, compared with the control group, 6 out of the 9 cytokines （MCP-1, MIP-1α, TNF-α, EGF, IL-8 and IP-10） were substantially increased in the BSS group （P〈0.05 or P〈0.01）, whereas only MIP-1α and IL-8 levels were elevated in the BDS group （P〈0.05 or P〈0.01） concurrent with lowered concentrations of SCD40L and IL-17 （P〈0.05）. In the WHS group, MIP-1α was the only cytokine whose level was evidently increased （P〈0.01）, in contrast to IL-17 which was decreased as compared with the control （P〈0.05）. The psoriatic patients overall owned higher levels of MIP-1 a and IL-8 in the circulation which were comparable among the 3 groups of CM syndromes （P〈0.01）. In contrast, TNF-α level of the BSS group was the highest among the three （P〈0.01）, followed by the BDS and the WHS groups. Conclusions： The expression profiles of cytokines in the circulation might not be necessarily identical for psoriatic patients with different CM syndromes. Accordingly, the serum concentrations of certain cytokines could potentially be used as the ancillary indices for the clinical classification of psoriatic CM syndromes.

Differential Gene Expression Profiles in Coronary Heart Disease Patients of Blood Stasis Syndrome in Traditional Chinese Medicine and Clinical Role of Target Gene

Objective:To investigate the differential gene expression profiles in coronary heart disease(CHD) patients of blood-stasis syndrome(BSS) by oligonucleotide microarray technique,and the clinical significance of target gene.Methods:Subjects were assigned to CHD patients with BSS(n=8),CHD patients without BSS (n=8),and BSS patients without CHD(n=8) based on coronary angiography and the diagnostic criteria of BSS. The sex- and age-matched healthy volunteers(n=8) were enrolled as the control group.Venous blood s...

Study on the Relationship between Blood Stasis Syndrome and Clinical Pathology in 227 Patients with Primary Glomerular Disease

To investigate the relationship between the severity of Chinese medicine(CM) bloodstasis syndrome(BSS) with clinical features and renal lesion indexes of the primary glomerular disease. Methods:An epidemiological survey was conducted to collect the data of 227 patients diagnosed as chronic primary glomerular diseases,and their severity of BSS were scored three days before renal biopsies were performed.The following clinical indexes were analyzed:age,course of glomerular diseases,24-h urine protein ration(Up...

The Change-Over of Yin-yang and Gene Regulation in Kidney Deficiency Syndromes

The present paper studies gene regulation in kidney deficiency syndromes from the simple Nephrotic Syndrome and with the principle of positive-negative regulation to control the change-over ofyin-yang, the modem molecular biological techniques can be used, such as gene chip, representational difference analysis （RDA） and gene sequence analysis, so as to investigate the inner relationship between the genes and kidney deficiency syndromes and prove the effect given by these genes on the pathophysiological status of change-over ofyin-yang in kidney deficiency syndromes. This philosophical approach and method can also be adopted for studies of the related genes in other TCM syndromes.

Constructing protein-protein interaction network of hypertension with blood stasis syndrome via digital gene expression sequencing and database mining

OBJECTIVE： To construct a protein-protein interaction（PPI） network in hypertension patients with blood-stasis syndrome（BSS） by using digital gene expression（DGE） sequencing and database mining techniques.METHODS： DGE analysis based on the Solexa Genome Analyzer platform was performed on vascular endothelial cells incubated with serum of hypertension patients with BSS. The differentially expressed genes were f iltered by comparing the expression levels between the different experimental groups. Then functional categories and e nriched pathways of the unique genes for BSS were analyzed using Database for Annotation, Visualization and Integrated Discovery（DAVID） to select those in the enrichment pathways. I nterologous Interaction Database（I2D） was used to construct PPI networks with the selected genes for hypertension patients with BSS. The potential candidate genes related to BSS were identif ied by comparing the number of relationships among genes. Confi rmed by quantitative reverse transcription-polymerase chain reaction（q RTPCR）, gene ontology（GO） analysis was used to infer the functional annotations of the potential candidate genes for BSS.RESULTS： With gene enrichment analysis using DAVID, a list of 58 genes was chosen from the unique genes. The selected 58 genes were analyzed using I2 D, and a PPI network was constructed. Based on the network analysis results, candidate genes for BSS were identifi ed：DDIT3, JUN, HSPA8, NFIL3, HSPA5, HIST2H2 BE, H3F3 B, CEBPB, SAT1 and GADD45 A. Verif ied through qRT-PCR and analyzed by GO, the functional annotations of the potential candidate genes were explored.CONCLUSION： Compared with previous methodologies reported in the literature, the present DGE analysis and data mining method have shown a great improvement in analyzing BSS.