Objective To analyze the clinicopathological features of bilateral primary breast cancer (BPBC) by molecular subtypes.Methods Clinical data of 145 BPBC patients were reviewed focusing on the clinicopathological features of different molecular subtype and the concordance of molecular subtype between first and second primary breast cancers.Results Of the first primary breast cancers ( FPBC),91 cases (62.8％ ) were Luminal A subtype,Luminal B subtype in 13 cases (9.0％ ),Human epidermal growth factor receptor 2 (HER-2) subtype in 14 cases (9.7％ ),triple negative breast cancer (TNBC) in 27 cases ( 18.6％ ).Of the second primary breast cancers ( SPBC ),Luminal A subtype was found in 93 (64.1％ ) cases,Luminal B subtype in 10(6.9％ ) cases,HER-2 subtype in 14(9.7％ ) cases and TNBC in 28( 19.3％ ) cases.Most TNBC patients were young ( age ≤ 50 ) with high frequency of grade Ⅲ in FPBC.Molecular subtypes do not vary with tumor size,clinical stage,lymph node status and pathological types ( P ＞ 0.05 ).Most FPBC of Luminal A and TNBC were concordant same subtypes in SPBC ( K ＞ 0.04 ),while Luminal B and HER-2 subtypes often had discordant phenotypes in SPBC ( K ＜ 0.04).BPBC were more likely to have concordant subtypes if the two tumors developed in short time interval.Conclusions The distribution and clinical leatures of each subtype in BPBC is similar to unilateral breast cancer.Patients whose FPBC are Luminal A or TNBC often have concordant phenotypes for their SPBC,a short time interval between two cancers also predicts concordance.

Objective To compare the mRNA expressions of interleukin (IL)-17 and IL-23 in peripheral blood of patients with psoriasis vulgaris versus healthy individuals,assess the relationship of these parameters with psoriasis area and severity index (PASI) score,and to investigate the therapeutic mechanisms of total glucosides of peony (TGP) for psoriasis vulgaris.Methods Fifty patients with psoriasis vulgaris and 40 healthy individuals were enrolled in this study.Of these patients,42 were treated with TGP of 600-900 mg twice a day for 8 weeks.Blood samples were obtained from all the healthy individuals,50 patients before treatment,42 patients after 4-week treatment,and 23 patients after 8-week treatment.Real-time fluorescence-based quantitative reverse transcription PCR (RT-PCR) was used to determine the mRNA expression levels of IL-17 and IL-23 in the blood samples.The severity of psoriasis was evaluated using PASI score before and after the treatment.Statistical analysis was done by t test,rank sum test,and Pearson correlation analysis using the SPSS16.0 software.Results The IL-17 and IL-23 mRNA expression levels (given in △Ct value) in the patients before treatment were significantly higher than those in the healthy controls (IL-17,-5.32 ± 0.80 vs.2.79 ± 0.76,t =47.71,P ＜ 0.05; IL-23,-5.43 ± 0.68 vs.-3.77 ± 0.86,t =10.38,P ＜ 0.05),and positively correlated with the PASI score (r =0.61,0.52 respectively,both P ＜ 0.05).A significant decrease was observed in the mRNA expression levels of IL-17 and IL-23 as well as PASI score in the 42 patients after 4-week treatment with TGP compared with those before treatment(IL-17,-2.24 ± 0.61 vs.-5.30 ± 0.78,t =20.40,P ＜ 0.05; IL-23,-1.97 ± 0.74 vs.-5.44 ± 0.68,t =21.69,P ＜ 0.05; PASI,5.8 ± 2.7 vs.9.4 ± 4.2,t =4.68,P ＜ 0.05),and in the 23 patients after 8-week treatment compared with those after 4-wek treatment(IL-17,-1.51 ± 0.78 vs.-2.21 ± 0.59,t =3.50,P ＜ 0.05; IL-23,-1.27 ± 0.81 vs.-1.89 ± 0.72,t =2.70,P＜ 0.05; PASI,3.8 ± 1.8 vs.7.3 ± 2.5,t =5.47,P＜ 0.05).Conclusions It seems that both IL-17 and IL-23 are involved in the pathogenesis of psoriasis vulgaris,and TGP treatment can reduce the mRNA expression levels of IL-17 and IL-23 as well as PASI score in patients with psoriasis vulgaris.

Objective:To research the application of flurbiprofen compound small dose fentanyl with self-control vein analgesia after laparoscopic cholecystectomy and the influence on blood coagulation function.Methods:102 cases with laparoscopic cholecystectomy who were treated in our hospital from November 2015 to November 2016 were selected and divided into the control group and the research group,with 51 cases in each group.The patients in the control group were treated with postoperative intravenous analgesia with low-dose fentanyl,while the patients in the research group were treated with postoperative intravenous analgesia with flurbiprofen ester compound low-dose fentanyl.Then the fibrinogen (Fg),activated partial prothrombin time (APTT),prothrombin time (PT),platelet count (PLT),substance P,5-hydrocarbon serotonin (5-HT),interleukin 6,8 (IL-6,IL-8) and complications between two groups were observed and compared.Results:Before treatment,there was no statistically significant difference about the Fg,APTT,PT,PLT,substance P,5-HT,IL-6 and IL-8 between two groups (P＞0.05);After treatment,the Fg,APTT,PT,PLT,substance P,5-HT,IL-6 and IL-8 increased in the two groups,while the research group was lower than that of the control group,and the differences were statistically significant (P＜0.05).The postoperative complication rate of research group was lower than that of the control group (P＜0.05).Conclusion:Flurbiprofen ester compound small dose fentanyl with self-control vein analgesia can relieve coagulation function,and inhibit the levels of inflammatory factors.

Histone deacetylases (HDACs) inhibition causes hyperacetylation of histones leading to growth arrest, differentiation and apoptosis of tumor cells, representing a new strategy in cancer therapy. Many of previously reported HDACs inhibitors are hydroxamic acid derivatives, which could chelate the zinc ion in the active site in a bidentate fashion. However, hydroxamic acids occasionally have produced problems such as poor pharmacokinetics, severe toxicity and low selectivity. Herein we describe the identification of a new series of non-hydroxamate HDACs inhibitors bearing diketo ester moieties as zinc binding group. HDACs inhibition assay and antiproliferation assays in vitro against multiple cancer cell lines were used for evaluation. These compounds displayed low antiproliferative activity against solid tumor cells, while good antiproliferative activity against human leukemic monocyte lymphoma cell line U937. Compound CPUYS707 is the best with GI50 value of 0.31 micromol x L(-1) against U937 cells, which is more potent than SAHA and MS-275. HDACs inhibition activity of these compounds is lower than that expected, further evaluation is needed.

Aim To investigate the effects of diallyl di-sulfide( DADS) on G2/M arrest in Chk1/MGC803 and Chk2/MGC803 cells so as to establish stable human gastric cancer MGC803 cells with overexpression of Chk1/2 gene. Methods The colony formation, flow cytometry, RT-PCR and Western blot were used to de-tect the proliferation, cell cycle, and expression of Chk1/2 mRNA and protein, p-Chk1/2, CDC25C and cyclinB1, respectively. Results The colony formation showed that the colony forming efficiency in Chk1/MGC803 and Chk2/MGC803 cells treated by 30 mg· L-1 DADS was lower than in control group and vector group ( P <0. 05 ) . Flow cytometry demonstrated that 41. 3%, 57. 4%, 68. 9% and 42. 9% of G2/M cells in Chk1/MGC803 were increased than in MGC803 and Chk2/MGC803 , respectively after treated by DADS in 12,24, 36 and 48 h(P <0. 05). At the same time, RT-PCR disclosed that expression of Chk1 and Chk2 mRNA had no marked change. Western blot showed that total proteins of Chk1 and Chk2 and p-Chk2 had invisible change, but expression of p-Chk1 was up-reg-ulated, and CDC25C and cyclinB1 were down-regula-ted time-dependently in Chk1/MGC803 cells ( P <0. 05 ) . Conclusion DADS arrests MGC803 cells at G2/M by increasing p-Chk1 expression to cause down-regulation of CDC25C and cyclinB1 simultaneously.

Objective: To explore the association of hypertriglyceridemic waist phenotype ( HTGW ) with impaired fasting glucose ( IFG ) and diabetes, so as to provide reference for the early prevention and control of diabetes. Methods: The survey was conducted among 35 to 75-year-old residents in 8 project sites in Jiangsu Province from 2015 to 2019. The information about demography and lifestyle was collected by the general information questionnaire and the primary screening questionnaire from the National Center for Cardiovascular Diseases; waist circumference, height, weight, triglyceride, high-density lipoprotein cholesterol, total cholesterol and fasting plasma glucose were measured. The multinomial logistic regression model was employed to analyze the association of HTGW with IFG and diabetes. Results: A total of 118 383 subjects were included, among whom 21 851 cases of HTGW, 27 245 cases of IFG and 22 899 cases of diabetes were identified, with the prevalence of 18.46%, 23.01% and 19.34%. The multinomial logistic regression analysis showed HTGW was statistically associated with IFG ( OR=1.414, 95%CI: 1.343-1.489 ) and diabetes ( OR=2.216, 95%CI: 2.098-2.341 ). Conclusion HTGW is associated with IFG and diabetes, which make it possible to be an indicator for screening and assessment of glucose abnormality in middle-aged and elderly population.

OBJECTIVETo study the endothelioid differentiation effect of Epimedin C on murine embryonic mesenchymal stem cells (C3H/10T1/2).

METHODSC3H/10T1/2 cells were cultivated in vitro. The cytotoxicity of Epimedin C at different concentrations was determined by MTT assay and crystal violet assay. Morphological changes were observed under microscope after treated with Epimendin C. The effect of Epimendin C on the cell cycle distribution was determined by flow cytometry. mRNA expression levels of endothelial markers, such as CD31, CD34, vascular endothelial zinc finger 1 (Vezf1), angiopoietin 1 (Ang1), and angiopoietin 2 (Ang2) were detected by semi-quantitative PCR. Protein expression levels of platelet endothelial adhesive molecule 1 (CD31), ecto-5'-nucleotidase (CD73), endothelial cell specific molecule-1 (ESM-1), and integrin β5 were determined by immunocytochemical (IHC) staining.

RESULTSEpimedin C could not affect the survival rate of C3H/10T1/2 cells at 1-30 μmol/L. Its cell cycle distribution was not significantly changed after treated by 30 μmol/L Epimedin C for 24 h. C3H/10T1/2 cells were differentiated to vascular endothelial cells by Epimedin C treatment, with significant morphological changes (whirlpool-like structure). PCR results indicated that mRNA levels of classic endothelial mark- ers, namely CD34, Vezf1, Ang1, and Ang2 were significantly increased in C3H/10T1/2 cells after treated with Epimedin C for 5 days (P < 0.05, P < 0.01). Protein expression levels of CD31, CD73, and ESM-1 were also positively expressed after treated with Epimedin C for 5 days, showing statistical difference when compared with those of the control group (P < 0.01, P < 0.05).

CONCLUSIONEpimendin C could induce C3H/10T1/2 cells to differentiate into endothelioid cells.

Animals ; Cell Differentiation ; drug effects ; Cell Line ; Cells, Cultured ; Flavonoids ; pharmacology ; therapeutic use ; In Vitro Techniques ; Mesenchymal Stromal Cells ; physiology ; Mice ; RNA, Messenger

OBJECTIVETo study the effect of Qianyang Recipe (QYR) on the Gan-yang hyperactivity syndrome (GYHS), the blood pressure, and correlated vascular regulatory factors of hypertension rat.

METHODSThirty SD rats were randomly divided into the normal control group, the model group, and the QYR group, ten in each. Hypertension rat model of GYHS was prepared using Aconiti Praeparata Decoction plus ephedrine plus salt water. Rats in the QYR group orally took QYR physic liquor, while distilled water was given to rats in the normal control group and the model group. They were medicated for 28 successive days. The facial temperature, the grip strength, and the systolic pressure were determined once every 7 days. Rats' irritable degree and feather color were observed and recorded once every 14 days. After the last administration the plasma renin (PR), angiotensin II (Ang II), aldosterone (ALD), atrial natriuretic peptide (ANP), calcitonin gene-related peptide (cGRP) were determined.

RESULTSCompared with the model group of the same phase, the facial temperature of rats in the QYR group significantly decreased on the 14th, 21th and 28th day after administration. The systolic pressure obviously decreased on the 21st day after administration. On the 28th day after administration symptoms such as irritability, dry hair were improved, and the Ang II level decreased. There was significant difference in all these changes (P<0.05, P<0.01).

CONCLUSIONSQYR could relieve GYHS rats' symptoms such as facial hotness, irritability, dry hair, and so on, and decrease the systolic pressure. Decreased Ang II level might be one of its mechanisms.

Aldosterone ; blood ; Angiotensin II ; blood ; Animals ; Atrial Natriuretic Factor ; blood ; Calcitonin Gene-Related Peptide ; blood ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypertension ; blood ; diagnosis ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Renin ; blood

Objective:To test the expression of Minichromosome maintenance complex component 7(MCM7) protein in hepato-cellular carcinoma(HCC) of different species including human, rat and tree shrew (tupaia) by cross-species oncogenomics approach, and to investigate the relationship between the expression of MCM7 and the development of hepatocellular carcinoma and its clinical significance. Methods:Western blot and Immunohistochemistry were applied to detect the expression levels of MCM7 protein in HCC tissues,corresponding HCC-adjacent liver tissues and normal liver tissues collected from different species including human, rat and tree shrew, respectively. The clinicopathologic factors were also analyzed with the results of Immunohistochemistry. Results:Western blot analysis showed that the expression of MCM7 protein in HCC tissues of human and rat were higher than that in corresponding HCC-ad-jacent liver tissues and normal liver tissues, respectively and significantly (P<0.05). However, the expression of MCM7 protein in HCC tissues of tree shrew were also higher than that in corresponding HCC-adjacent liver tissues and normal liver tissues, but no significant difference was found among three types of tissues (P>0.05).There was also no significant difference between HCC-adjacent liver tis-sues and normal liver tissues in three species (P>0.05). Immunohistochemical analysis showed that MCM7 protein was mainly ex-pressed in nucleus of HCC cells, and the positive rate of MCM7 protein in HCC tissues of human, rat and tree shrew were significantly higher than that in corresponding HCC-adjacent liver tissues and normal liver tissues, respectively (P<0.05). However, no significant difference was found between HCC-adjacent liver tissues and normal liver tissues (P>0.05). Moreover, the protein level of MCM7 was intimately related to patient's HCC stage, extrahepatic metastases and postoperative recurrence (P<0.05). Conclusion:MCM7 protein might play a pivotal role in hepatocarcinogenesis. In addition, it was probably related to patient's HCC stage, extrahepatic metastases and postoperative recurrence. It seems very likely that MCM7 may be applied as a new molecular target in HCC prevention and treat-ment.

ObjectiveThis study evaluates the feasibility of intensity-modulated radiation therapy (IMRT) to treat patients with 1 -5 brain metastases from non-small cell lung cancer (NSCLC).Methods 30 IMRT patients with brain metastases for NSCLC studied retrospectively.Whole brain radiotherapy plus three-dimensional conformal radiotherapy (WBRT + 3DCRT) and WBRT plus stereotactic radiotherapy ( WBRT + SRT) plans were generated.Planning target volume ( PTV ) and organs at risk dose were measured and compared by dose volume histogram.Differences were analyzed in the three techniques by Wilcoxon Z -test.Results D99％ of the shoulder ( D99％-D90％ ) from IMRT were higher than from WBRT +3DCRT and WBRT+SRT in all cases.From D15％ of slope (D90％-D10％) to D5％ of tail (D10％ -D1％ ),IMRT were lower than WBRT + 3DCRT and WBRT + SRT ( Z =- 4.72,P =0.000 and Z =- 4.72,P =0.000).D10％ and D5％ of IMRT were (35.1 ±1.42) Gy and (37.7 ±2.91) Gy,WBRT +3DCRT were (36.5±2.86) Gy and ( 39.1 ± 3.56) Gy ;WBRT + SRT were (36.2 ± 2.57) Gy and ( 38.7 ± 3.67) Gy.IMRT vs WBRT+ 3DCRT and WBRT + SRT were significant ( Z=-3.18,-3.18,P=0.001,0.001 and Z=- 4.11,- 3.02,P =0.000,0.002) in 13 patients with 3 - 5 brain metastases.The total mean monitor units were 14756.3,9614.8 and 9043.2 for IMRT,WBRT +3DCRT and WBRT + SRT plans,respectively,with a 38.7％ reduction from IMRT to WBRT + SRT (Z =-4.78,-4.78,P =0.000,0.000).The brain doses around metastases were similar in the three techniques with 1 -2 metastases,but IMRT was the best with 3 -5 metastases.ConclusionsIMRT can advance brain metastases dose and improve the planning target minimum dose and spare the dose around brain metastases.Only IMRT is the best choice for just sparing the dose around brain metastases among 3 -5 brain metastases.