Objective:To explore the mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia using network pharmacology; To verify the mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia through animal experiments.Methods:The active components and potential targets of Shiwei Chaihu Shugan Powder were searched in TCMSP and Uniprot databases. Breast hyperplasia genes were searched in GeneCards and OMIM databases. The intersection targets were obtained by online tool Venny, and the "drug-component-target" network was constructed by Cytoscape 3.8.2 software. The protein interaction (PPI) network was constructed using the String platform, and GO function and KEGG pathway enrichment analysis were performed using the DAVID annotation database. Molecular docking was performed using PDB, PubChem database, PyMOL 2.1 and AutoDockvina 1.2.5 software to predict the biological mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia. Rats were divided into blank group, model group, tamoxifen group and Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups according to the random number table method, with 6 rats in each group. Except for the blank group, the other groups were prepared with the modified estrogen-progesterone-induced rat mammary hyperplasia model. Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups were intragastrically administered with Shiwei Chaihu Shugan Powder solution at 7.425 g/kg, 14.850 g/kg, and 29.700 g/kg respectively, while the tamoxifen group was intragastrically administered with 2.1 mg/kg tamoxifen. The blank group and the model group were intragastrically administered with the same volume of drinking water, once a day, for consecutive 28 d. The thickness of the mammary gland was measured by small animal ultrasound. The height and width of the nipples were measured by vernier calipers. The levels of serum E2 and P were detected by ELISA. The morphology of mammary tissue was observed by HE staining. The expressions of ERα, ERβ, SRC-1 and CBP/p300 proteins were detected by Western blot.Results:A total of 92 active components and 274 disease-drug intersection targets were screened out. GO functional enrichment analysis showed that Shiwei Chaihu Shugan Powder was closely related to positive regulation of gene expression, positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, negative regulation of apoptosis process, response to heterogeneous stimulation, and regulation of hormone levels. KEGG enrichment analysis showed that the core targets might be related to NF-κB signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, PI3K/Akt signaling pathway, and regulating hormone levels. Molecular docking results showed that the core components had a good binding energy with the core target and a stable conformation. Compared with the model group, the thickness of the mammary gland in the tamoxifen group and Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups decreased ( P<0.01), the serum P level increased ( P<0.05), the expressions of ERα, SRC-1, and CBP/p300 proteins decreased ( P<0.01), and the expression of ERβ protein increased ( P<0.01); the height of the nipples in the Shiwei Chaihu Shugan Powder medium- and high-dosage groups and the tamoxifen group decreased ( P<0.01), and the serum E2 level increased ( P<0.05). Conclusion:Shiwei Chaihu Shugan Powder may play a role in the treatment of breast hyperplasia by regulating the levels of estrogen and related proteins.

Aim To study the effects of telmisartan upon serum calcineurin.Methods 92 male SD rats with the same age were randomly divided into control group (N), sham operation group (S), 2K1C+distilled water group (K) and 2K1C+telmisartan group (T).S rats were performed the open-abdomen surgery without being restricted any renal artery, but the K and the T rats were restricted their left renal artery. Beginning from the third week after the surgery, the K rats started to be treated with the intragastric infusion of distilled water 10 ml·(kg·d)~(-1) , while the T rats with telmisartan 10 mg·(kg·d)~(-1) .And after being treated for 2, 4 and 8 weeks, rats were respectively measured the systolic blood pressure (SBP), the diastolic blood pressure (DBP) of the abdominal aorta. Before and after the operation, ultrasonography with probe of 7.5 MHz was used to obtain the structure and functional indexes, such as IVSd, IVSs, LVPWd, and serum calcineurin were evaluated by ELISA and colorimetric assay kit.Result Compared with the S group and the N group, ① the results of blood pressure (SBP, DBP) were significantly higher in K group (all P <0.01), after use of telmisartan, blood pressure was significantly reduced(P <0.01);② the thickness of interventricular septal and left ventricular posterior wall at the end of diastolic and systolic were significantly higher in K group (all P <0.01), after use of telmisartan, the thickness of those declined(all P <0.01);③ the level and activity of serum calcineurin were significantly higher in K group (all P <0.01), after use of telmisartan, the level and activity of calcineurin significantly fell(P <0.01).Conclusion The serum calcineurin of artery was also raised in the left ventricular remodeling. Telmisartan ameliorates ventricular remodeling effectively, which may be associated with decreasing the expression of artery serum calcineurin.

OBJECTIVETo explore the linkage relationship between specific genetic markers and arrhythmogenic right ventricular cardiomyopathy (ARVC) in Chinese pedigrees.

METHODSThe microsatellite genetic markers D2S152, D14S252, and D10S1664 were studied for their linkages to ARVC in five Chinese ARVC pedigrees and a normal population of 121 Chinese individuals. Genomic DNA of the pedigrees and normal population was amplified using PCR techniques. Denaturing polyacrylamide sequencing gel (4%) electrophoresis was used to detect microsatellite repeat polymorphisms. Gels were silver-stained. A classical linkage analysis program was used assuming models of autosomal dominance and recession.

RESULTSThe logarithm of the odds (LOD) scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were 2.174, -0.589, -infinity, - (indicating that linkage is not supported in this mode), and -infinity respectively in autosomal dominant model (recombination fraction = 0.000 respectively)and were -infinity, -infinity, -infinity, -infinity, and 0.182 respectively in the autosomal recessive model. The LOD scores of D14S252 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -, -infinity, -, and 0 respectively in autosomal dominant model, and were -infinity, -0.812, -infinity, -infinity, and 0.087 respectively in autosomal recessive model. The LOD scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -0.539, -, and 0.602 respectively in autosomal dominant model and were -, -infinity, -infinity, -infinity, and - infinity respectively in autosomal recessive model.

CONCLUSIONSThe LOD score for D2S152 in the LW pedigree was 2.174, indicating that the chance of linkage is about 150:1. This suggests that there is a possible ARVC-related gene near this marker. There were no clear linkage relationships between ARVC and D10S1664 and D14S252 in this family, and no linkages between ARVC and any of the three genetic markers in the other four families. These results also suggest that there is genetic heterogeneity in LW and in the other pedigrees.

Arrhythmogenic Right Ventricular Dysplasia ; genetics ; Asian Continental Ancestry Group ; China ; Female ; Genetic Linkage ; Genetic Markers ; Humans ; Lod Score ; Male ; Microsatellite Repeats

OBJECTIVELow or moderate consumption of red wine has a greater benefit than the consumption of other beverages in the prevention of atherosclerosis and coronary heart disease and this is increasingly attributed to the polyphenol compounds in red wine, such as resveratrol. In the present study, we investigated the effect of resveratrol on platelet aggregation in vitro and in vivo.

METHODSPlatelet aggregation in rabbits and normal subjects was measured using Born's method.

RESULTSResveratrol, at 10 - 1000 micromol/L, significantly inhibited platelet aggregation in vitro induced by collagen, thrombin, and ADP in healthy subjects. The inhibitory effect was concentration-dependent. Hypercholesterolemia induced by high-cholesterol diet enhanced ADP-induced platelet aggregation. Resveratrol 4 mg x kg(-1) x d(-1) inhibited ADP-induced platelet aggregation in vivo despite no changes in serum lipid levels.

CONCLUSIONSResveratrol inhibits platelet aggregation both in vitro and in vivo. This may be one of the mechanisms by which resveratrol prevents atherosclerosis.

Animals ; Arteriosclerosis ; prevention & control ; Cholesterol, LDL ; blood ; Humans ; Lipids ; blood ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; Rabbits ; Stilbenes ; pharmacology

OBJECTIVETo evaluate the safety and efficacy of the Amplatzer septal occluder for transcatheter closure in patients with secundum atrial septal defect (ASD II).

METHODSPatients with clinically confirmed ASD II were recommended for transcatheter closure of ASD II.

RESULTS30 ASD II patients (20 females) underwent transcatheter closure at a median age of 18.4 years (5-55 years). Both the stretched diameters of ASDs and the sizes of the devices were from 18 to 34 mm (25 +/- 7 mm). The successful placement rate was 100%. The rest shunt documented by color Doppler, was immediately after implantation in 40% of patients, in 9.9% after 24 hours, and in 3.3% trace at 3 months. No serious complications were observed. There was improvement in symptoms and in cardiac size. Septal motion abnormalities normalized in all patients after 3 months follow-up.

CONCLUSIONThe Amplatzer septal occluder is a safe and effective device for transcatheter closure of ASD II. Long-term follow-up is still required before widespread clinical use can be recommended.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Heart Septal Defects, Atrial ; surgery ; Humans ; Male ; Middle Aged ; Surgical Instruments

OBJECTIVETo investigate changes in the expression of sarcoplamic reticular Ca(2+)-ATPase (SERCA) and IP(3)-I receptors (IP(3)R(1)) mRNA in patients with atrial fibrillation.

METHODSThirty-eight patients with mitral stenosis undergoing open heart surgery were studied. 100 mg of atrial tissue was obtained during surgery from the right appendage and the right atrium. The amount of messenger ribonucleic acid (mRNA) amount of SERCA and IP(3)R(1) was measured by reverse transcription-polymerase chain reaction (RT-PCR) and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase (GAPDH).

RESULTSLevels of mRNA expression of SERCA in patients with AF, as compared with subjects in sinus rhythm, was lower and that of IP(3)R(1) was higher. The longer AF was sustained, the higher the levels of mRNA. There was no significant difference between right atrial free wall and right appendage.

CONCLUSIONSThe expression changes of SERCA and IP3R mRNA may correlate with the initiation or maintenance of AF.

Adult ; Aged ; Atrial Fibrillation ; genetics ; pathology ; Calcium Channels ; genetics ; Calcium-Transporting ATPases ; genetics ; Female ; Gene Expression ; Humans ; Inositol 1,4,5-Trisphosphate Receptors ; Male ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Receptors, Cytoplasmic and Nuclear ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sarcoplasmic Reticulum Calcium-Transporting ATPases