AIMTo study the regulation mechanism of GP on plasma lipoprotein metabolism and To explore its mechanism of anti-lipoperoxidation in the experimental hyperglycemia rats.

METHODSThe rats were raised with high fat diet for six weeks,and the model of hyperglycemia was then established. After that, those rats were treated with high or low dose of GP and xuezhikang as a masculine comparison for four weeks. Then, those rat were executed, and detected the plasma TC, TG, LDL-C, HDL-C, GSH-Px, at the same time the SOD, CAT and MDA concentration also be mensurated.

RESULTSThe results showed that high and low dose of GP could decrease the concentration of serum LDL-C, cholesterol and triglyceride remarkably and raise the concentration of HDL-C. The activity of GSH-Px, SOD and CAT in GP groups were promoted and the level of MDA was decreased distinctly.

CONCLUSIONThe GP can therapy the abnormity of serum lipid and has obviously anti-lipoperoxidation affection.

Animals ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; Gynostemma ; Hyperlipidemias ; drug therapy ; metabolism ; Lipid Peroxidation ; Lipids ; blood ; Lipoproteins, HDL ; blood ; Male ; Phytotherapy ; Plant Extracts ; therapeutic use ; Rats ; Rats, Wistar ; Triglycerides ; blood

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer (TNBC). Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2) every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response (pCR), which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Thirty-nine (90.7%) patients were at clinical stages IIB-IIIC. Thirty-seven (86%) completed 4-6 cycles of preoperative chemotherapy, and objective response rate (ORR) was 81.4% (35/43). Forty-two patients underwent radical surgery subsequently. The pCR rate was 14.3% (6/42). The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting (88.4%, 38/43) and neutropenia (88.4%). After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally advanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemoradiotherapy, Adjuvant ; methods ; Disease-Free Survival ; Epirubicin ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; methods ; Neoplasm Recurrence, Local ; pathology ; prevention & control ; Neoplasm, Residual ; pathology ; prevention & control ; Paclitaxel ; administration & dosage ; Taxoids ; administration & dosage ; Treatment Failure ; Treatment Outcome ; Triple Negative Breast Neoplasms ; drug therapy ; pathology

OBJECTIVE Paeoniflorin (PF) and albiflorin (AF) are the major active components of total peony glucosides(TPG)from Paeonia lactiflora Pal,which have many biological activities such as anti-inflammatory, antioxidation and anti-hypertension effects. The drug-drug pharmacokinetic interaction among PF,AF and TPG,the pharmacokinetic comparisons of AF between hypoxia and normoxia,the transport of AF cross the blood-brain barrier cell model and the transport of AF/PF/TPG cross Caco-2 cell model were investigated.METHODS A highly sensitive and rapid UPLC-MS method with multiple-reaction monitoring(MRM)scanning via electrospray ionization(ESI)source operating both in the positive and negative ionization mode was successfully developed and validated for simultaneous quantitation of PF and AF in rat plasma after an oral administration of PF,AF and TPG. RESULTS The validated and developed UPLC-MS/MS method was successfully applied to simultaneously determine the AF and PF concentration in rat plasma and investigate pharmacokinetic interactions after a single intragastrical ad-ministration of PF,AF,co-administration of PF with AF and TPG,respectively.The elimination of both PF co-administered with AF and PF in TPG were slower than those for PF alone and the distribution in the tissues was wider.The combination of PF with AF or TPG could significantly increase the values of the AUC, MRT and t1/2of the drug PF, and reduce the values of CL of PF. From a comparison of the main pharmacokinetic parameters among AF alone, AF combined with PF and AF in TPG, the values of the MRT and t1/2of AF in TPG were greater than that of AF alone,and there were statistically signifi-cant differences in these parameters(P<0.05,P<0.01).It was also noticed that AUC and Cmaxof PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The multiple active components in TPG may lead to DDIs between some P-gp substrates. CONCLUSION The clinical performance of total peony glucosides would be better than that of single constitute. The outcomes of the study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.

OBJECTIVETo analyze the relevance between lymph node status and pathological response after neoadjuvant chemotherapy and survival in breast cancer patients.

METHODSThe clinicopathological data of 653 needle biopsy proved breast cancer patients, who underwent neoadjuvant chemotherapy and surgery in our hospital from July 1998 to April 2012, were retrospective analyzed.

RESULTSThe median follow up time was 59.3 months. The 653 cases were classified into ypN0 (242 cases), ypN1 (182 cases), ypN2 (135 cases), and ypN3 (94 cases) stages, and the 5-year overall survival rates in the four groups were 93.4%, 93.4%, 87.4%, and 83.0%, respectively. The Log rank test showed a significant difference in the overall survival rates between the ypN0, ypN1, ypN2 stages and ypN3 stage (P=0.046). No significant differences were observed between the disease free survival (DFS) rates in the four groups (P>0.05). Multivariate analysis indicated that the postoperative pathological response of metastatic lymph nodes was a major prognostic factor affecting the overall survival and disease-free survival (RR=1.051, P=0.007; RR=1.028, P=0.028).

CONCLUSIONThe stage and pathological response of axillary lymph nodes after neoadjuvant chemotherapy are effective indicators for predicting the OS and DFS in breast cancer patients.

Axilla ; Breast Neoplasms ; drug therapy ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Survival Rate

OBJECTIVETo evaluate the efficacy, safety and survival of combination of carboplatin plus paclitaxel as neoadjuvant chemotherapy (NACT) for patients with locally advanced triple-negative breast cancer (TNBC), and explore an optimal regimen for TNBC.

METHODSPatients with core needle biopsy confirmed pathological diagnosis of IIA ∼ IIIC invasive breast cancer, negative for estrogen and progesterone receptors and HER2 by immunohistochemistry, and with indication for NACT were eligible in this study. The biopsy tumor tissues were tested for CK5/6, CK14, EGFR and Ki67. The patients received paclitaxel 175 mg/m(2) on day 1, carboplatin at an area under the curve 5 mg×min/ml on day 2 of every 21 days. The clinical response was evaluated every 2 cycles according to Standard RECIST 1.0 criteria and surgery was done after four to six cycles. Pathological complete remission (pCR) was defined if absence of invasive tumor in the breast and axillary lymph nodes samples or residual carcinoma in situ only.

RESULTSOverall, thirty-one patients were enrolled from January 2008 to November 2010. The median age was 51 years and 83.9% of the patients were diagnosed as stage IIB to IIIC diseases. 30 Patients completed chemotherapy as planed while one patient changed regimen due to paclitaxel allergy. Twenty-eight patients could be evaluated for clinical efficacy, of which CR, PR, SD, PD were achieved in 4, 20, 3 and 1 women, respectively. The objective response rate was 85.7%. The expression rate of CK5/6, CK14 and EGFR were 88.9% (24/27), 59.3% (16/27) and 63% (17/27), respectively. Among 27 patients who received modified radical mastectomy or breast-conserving surgery, 11 patients obtained pCR, with a pCR rate of 40.7% (95%CI 22.2% - 59.3%). Five of six CK5/6- and CK14-positive patients achieved pCR. All the 31 patients could be evaluated for toxicity according to the NCI-CTC v3.0 criteria. The major toxicities were neutropenia (93.5%), vomiting (45.2%) and ALT/AST increase (32.3%), and grade 3-4 toxicities accounted for 74.2%, 3.2%, 0, respectively. Until December 2011, at a median follow-up of 28.9 months (range 5 - 47.9), eight patients developed recurrence including 5 patients died. Among 11 patients with pCR, one suffered from lung metastasis at 45 months after diagnosis and survived with tumor until now. The other ten were alive and disease free. The 3-year DFS and OS were 62% and 74.7%, respectively.

CONCLUSIONSAs a neoadjuvant treatment for triple-negative breast cancer, carboplatin plus paclitaxel regimen achieves notable higher objective response rate and pCR rate compared with the anthracycline plus paclitaxel regimen reported in the literature, and is well tolerable. It is an optimized regimen for TNBC.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Biopsy, Large-Core Needle ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Carboplatin ; administration & dosage ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; secondary ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neutropenia ; chemically induced ; Paclitaxel ; administration & dosage ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Remission Induction ; Survival Rate ; Young Adult

OBJECTIVETo evaluate the effects of nasal mometasone furoate on moderate to severe allergic rhinitis.

METHODSPatients with moderate to severe allergic rhinitis were enrolled and received mometasone furoate nasal spray 200 microg once daily for four weeks. Four hundreds and sixty-three patients completed the study. We weekly interviewed the patients to evaluate the symptoms, and the affection of disease on night sleep and daily life. Mini Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ) and Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) were used to evaluate the quality of life.

RESULTSThe individual and total symptomatic scores of week 1, week 2 and week 4 decreased compared with baseline. The scores of Mini-RQLQ and NRQLQ of week 1, week 2 and week 4 decreased compared with baseline too. The scores of the next visit were significantly lower than those of the previous visit (P < 0.01).

CONCLUSIONSA four-week administration of mometasone furoate nasal spray can effectively treat allergic rhinitis.

Administration, Intranasal ; Adolescent ; Adult ; Aged ; Anti-Allergic Agents ; administration & dosage ; therapeutic use ; Child ; Female ; Humans ; Male ; Middle Aged ; Mometasone Furoate ; Pregnadienediols ; administration & dosage ; therapeutic use ; Quality of Life ; Rhinitis, Allergic, Perennial ; drug therapy ; Surveys and Questionnaires ; Young Adult

Objective To investigate the expression of semaphorin 3A (Sema3A) and its receptor neuropilin-1 (NRP-1) in gastric cancer and its correlation with microvessel density (MVD), and then to explore the effect of recombinant human Sema3A on angiogenesis of gastric cancer and the associated mechanisms. Methods Forty cases of gastric cancer tissues and its corresponding adjacent normal tissues were used to detecte the expression of Sema3A, NRP-1 and MVD in tissues by immunohistochemistry method . The expression level of Sema3A in serum of gastric cancer patient group and normal control group were measured by Enzyme-linked immuno-sorbent assay (ELISA). Western blotting was used to detect the expression of Sema3A and NRP-1 in five gastric cancer cell lines (MGC-803,HGC-27,MKN-28,SGC-7901,MKN-45) and human gastric mucosal epithelial cell (GES-1). Transwell chamber was used to construct non-contact in vitro co-culture system, in which the effects of different concentrations of recombinant human Sema3A on angiogenesis in gastric cancer were analyzed by tube formation assay preliminarily. The expression levels of vascular endothelial growth factor receptor 2 (VEGFR2) and NRP-1 in co-culture system were detected by Western blotting. Results The expression levels of Sema3A in gastric cancer tissues, cell lines and patient serum were significantly lower than that in the control group(P<0. 05), while the expression of NRP-1 in gastric cancer tissues and MKN-28 cells was significantly increased, and both of them were associated with TNM staging of gastric cancer (P < 0. 05) . In vitro co-culture system, The tube forming abilities of human umbilical vein endothelial cell (HUVEC) were decreased in recombinant human Sema3A treated group, and this phenomenon was concentration dependent. The expression of VEGFR2 protein was down-regulated by recombinant human Sema3A. Conclusion The expression of Sema3A was decreased in gastric cancer tissues, cell lines and patient serum, and negatively correlated with microvessel density. The recombinant human Sema3A could inhibit the angiogenesis of gastric cancer in vitro, which may be related to down-regulation of VEGFR2 protein expression.

OBJECTIVE: To analyze the effect of Xuezhikang on the markers of the serum lipid levels of cholesterol synthesis and absorption in early menopausal women with hypercholesterolemia, and preliminarily explore its lipid-lowering mechanism. METHODS: A total of 90 early menopausal women with hypercholesterolemia were enrolled from December, 2014 to May, 2016 from Beijing Anzhen Hospital, Capital Medical University, who were randomly allocated to receive Xuezhikang (1200 mg/d, orally) or atorvastatin (10 mg/d, orally) according to a random number table. Serum levels of some related biomarkers, including cholesterol synthesis markers (squalene, dihydrocholesterol, dehydrocholesterol, and lathosterol), and absorption markers (campesterol, stigmasterol, and sitosterol) as well as safety indices were obtained at baseline and after 8 weeks of the intervention. RESULTS: Eight weeks after treatment, both Xuezhikang and atorvastatin significantly reduced the levels of total cholesterol, triglycerides, low density cholesterol compared to baseline (all P<0.01). Xuezhikang significantly reduced the levels of squalene, dehydrocholesterol and lathosterol compared to baseline (all P<0.01), but atorvastatin only significantly reduced the level of squalene (P<0.01), compared to baseline. All cholesterol absorption markers showed no significant differences before and after treatment (P>0.05), however, a more obvious downward trend was shown in the Xuezhikang group. In addition, all the safety indices showed no significant differences between the two groups. Although the creatinekinase level in the Xuezhikang group was significantly higher, it remained within the safe range. CONCLUSIONS Xuezhikang may have more comprehensive effects on the markers of cholesterol synthesis and metabolism in early menopausal women with hypercholesterolemia through ergosterol and flavonoids in its "natural polypill."
Biomarkers ; Cholesterol ; Drugs, Chinese Herbal ; Female ; Humans ; Hypercholesterolemia/drug therapy* ; Menopause

Objective : To investigate the factors influencing the pregnancy outcomes during frozen-thawed embryo transfer (FET) cycles in patients with polycystic ovary syndrome (PCOS) . Methods : A retrospective analysis was conducted on patients ’data from 882 FET cycles . According to the pregnancy outcome , the patients were divided into non-implantation group (Group A) , abortion group ( Group B1) and live birth group ( Group B2) . Clinical data and laboratory parameters were compared among the three groups , and ordered Logistic regression analysis was used to study the factors influencing pregnancy outcomes after FET. Patients were also divided into four groups (C1-C4) based on the number of high-quality embryos obtained (0 - 3 , 4 - 6 , 7 - 10 , ≥11) , and their clinical data and laboratory parameters were compared . Results : The clinical pregnancy rate , live birth rate , and miscarriage rate in the 882 treatment cycles were 71 . 09% (627/882) , 61 . 68% (544/882) , and 13 . 24% (83/627) ,respectively. Single-factor analysis showed significant differences in body mass index (BMI) , infertility type , human chorionic gonadotropin (hCG) day estradiol ( E2 ) level , number of retrieved oocytes , and number of high-quality embryos among Groups A , B1 , and B2 (P < 0. 05) . Further multiple Logistic regression analysis revealed that BMI(OR = 1 . 046 , 95% CI:1 . 001 - 1 . 093 , P = 0. 044) and a history of previous pregnancy(OR = 1 . 417 , 95% CI:1 . 030 - 1 . 950 , P = 0. 032) were independent risk factors for successful FET in PCOS patients , while an increased number of high-quality embryos was an independent protective factor for successful pregnancy. Based on the results of Group B2 , compared to Group A , OR = 0. 920 , 95% CI:0. 880 - 0. 962 , P = 0. 000;compared to Group B1 , OR = 0. 923 , 95% CI:0. 862 - 0. 988 , P = 0. 022 . Compared with the other three groups( C1-C3) , the total amount of gonadotropin (Gn) in the C4 group was the lowest and the number of oocytes obtained was the highest (P < 0. 05) . Multiple comparisons showed that Group C4 had lower BMI , follicle-stimulating hormone (FSH) , very low-density lipoprotein ( vLDL) levels , a higher luteinizing hormone and follicle-stimulating hormone ( LH/FSH) ratio compared to Group C1 (P < 0. 05) . Group C4 had lower fasting insulin (FINS) and homeostasis model assessment of insulin resistance ( HOMA-IR) levels compared to Group C3 , and higher high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A1) levels compared to Groups C2 and C3 (P < 0. 05) . Conclusion BMI , the history of previous pregnancy and the number of high-quality embryos were both independent factors for predicting pregnancy outcomes in PCOS patients undergoing FET cycles . Patients with a higher number of high-quality embryos have a higher clinical pregnancy rate during FET cycles .