Aim To study the molecular mechanism of retinal toxicity induced by N-methyl-N-nitrosourea (MNU) in SD rats. Methods A single intraperitoneal injection of 60 mg?kg~(-1) MNU was given to 50-day-old female SD rats. After MNU treatment for different times, the rats were sacrificed and both eyes were enucleated immediately and processed for histological examination. The apoptotic index of photoreceptor cells was calculated by TUNEL labeling and the expression of c-jun and c-fos genes was detected by RT-PCR technique. Results After the application of MNU for 24 h,the disorientation of photoreceptor outer segments was seen. The outer nuclear layer and photoreceptor layer were almost completely lost at 7 d. Apoptosis had already started at 12 h post-MNU and peaked at 24 h. MNU time-dependently up-regulated the expression of c-jun and c-fos genes. Conclusion MNU has a toxic effect on retina by up-modulating expression of c-jun and c-fos genes to promote photorecptor cells apoptosis.

Objective To investigate the mechanism of the toxic effect of N-methyl-N-nitrosourea (MNU) on photoreceptor cell apoptosis of rat′s retina. Methods Thirty 50-day-old female Sprague-Dawley ( SD ) rats were intraperitoneally injected with MNU (60 mg/kg) and were put to death by dislocation of cervical vertebra 12, 24, 48, and 72 hours and 7 days after the injection, respectively. The photoreceptor cell apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and transmission electron microscope. The expression of proliferating cell nuclear antigen (PCNA), vimentin and glial fibrillary acidic protein (GFAP) was detected at different time after injection by immunohistochemical methods. Results The apoptotic index of the retina in the posterior pole was (33.6?2.3)%, (46.5?5.7)%, (20.1?5.3)%, (8.2?3.6)% and (2.5?1.3% at the 12th, 24 th, 48 th, and 72nd hour and on the 7th day, respectively, after injection. Karyopyknosis was found in most photoreceptor cells 24 hours after injection. The expression of PCNA was found in internal granular layer and between internal granular layer and choroid 24 hours after injection, reached the peak after 72 hours, and reduced obviously after 7 days. The positive expression of GFAP and vimentin was found in internal and external granular layer 24 hours after injection, reached the peak after 72 hours, and reduced obviously after 7 days. Conclusion MNU may selectively lead the photoreceptor cell apoptosis and proliferation of M?ller cells.

Aim To explore the effects and its mechanisms of ginsenoside-Rg1 on level of t-PA and PAI-1.Methods Type 1 plasminogen activator inhibitor(PAI-1) and tissue type plasminogen activator(t-PA) activity in plasma were assayed using chromogenic substrate.Results The results showed that ginsenoside-Rg1 in vitro or in vivo significantly inhibited PAI-1activity,while increased t-PA activity.These effects were concentration-dependent.Intravenous Panax notoginsenoside Rg1 at 30,60,120 and 240 mg?kg~(-1) markedly suppressed PAI-1 level in plasma as well as platelet-released substances stimulated by thrombin,while increased plasma t-PA activity.And release level of PAI-1 owing to blood platelet was greatly decreased by ginsenoside-Rg1.Conclusion Ginsenoside-Rg1 showed potent antithrombosis due to the inhibition of PAI-1 and increase of t-PA.It might also be a advantagous mechanism to its antithrombsis.

BACKGROUND: Retinitis pigmentosa (RP) is a non-inflammatory, bilaterally progressive, retinal degeneration characterized by loss of photoreceptor cells via an apoptotic mechanism, and it eventually leads to blindness.Research shows that the traditional Chinese medicines of Astragalus has great prospect on blocking the progression of RP disease.OBJECTIVE: To observe the protective effect of Astragalus on N-methylN-nitrosourea (MNU)-induced retinal damage in Sprague-Dawley (SD) rats and provide the optimal treatment for RP in humans.DESIGN: Randomized controlled experiment.SETTING: School of Pharmaceutical Sciences, Xinxiang Medical College.MATERIALS :The experiment was completed in Pharmacological Laboratory of Zhongshan Ophthalmic Centre, Sun Yat-sen University between March to December 2004. Totally 114 female SD rats were purchased from the Animal Center of Zhongshan Medical College, Sun Yat-sen University.MNU was purchased from Sigma Company of America. Astragalus injection was purchased from Chengdu Diao Jiuhong Pharmaceutical Factory (Batch No. Z99060535, 2 mL/ampoule, main ingredient: Astragalus).METHODS: Among 114rats, 30 were for morphometric analysis of retinal layers, 30 were for detection of apoptosis and 54 were for detection of NF-κB p65 activity. All of them were randomly divided into different groups and each group had 6 rats. Astragalus at doses of 2.5, 5 and 10 g/kg were injected intraperitoneally into 47-day rats once a day. Meanwhile, a single intraperitoneal injection of 60 mg/kg MNU was given to 50-day rats in model and Astragalus groups. At different intervals after MNU treatment,the animals were sacrificed. Retinal damage was evaluated based on retinal thickness, the apoptotic index of the photoreceptor cells was detected by TUNEL labeling and the DNA-binding activity of NF-κB p65 was analyzed according to transcription factor assay kit.MAIN OUTCOME MEASURES: Comparison of retinal thickness, apoptotic index and the activity of nuclear NF-κB p65.RESULTS: Totally 114 rats entered the result analysis. Pretreatment with Astragalus could dose-dependently suppress MNU-induced photoreceptor cell loss and decreased the apoptotic index. Astragalus at dose of 10 g/kg also time-dependently up-regulated the activity of nuclear NF-κB p65.However, protective effect of Astragalus on MNU-induced central retinal damage was not found.CONCLUSION: Astragalus partially protects against MNU-induced retinal damage by up-modulating the activity of nuclear NF-κB p65 to inhibit apoptosis of photoreceptor cells in a dose-dependent manner.

To promote the construction of first-class disciplines of "Double First-Class" universities in China, the construction of a comprehensive evaluation system was explored, so as to provide suggestions for the development of these disciplines.Essential Science Indicators (ESI), InCites and Derwent Innovation Index databases, together with range transformation method and entropy weight method, were employed to analyze the data in the field of pharmacology and toxicology from some universities; the construction approaches and index performance of the system were studied. The score performances of the sample universities in the index system are different from their ESI rankings, suggesting that the system has certain practical value.ESI rankings cannot fully reflect the development levels of disciplines, while the multi-dimensional index evaluation system can overcome this shortcoming to a certain extent.This paper establishes an evaluation system with published papers and granted patents as the main evaluation objects, covering as many multi-angle indicators of scientific research output as possible, and trying to overcome the disadvantages due to lack of information in a single or few index systems.It is suggested that universities should formulate their discipline development plans from the perspectives of publishing high-quality original research results, leading or widely participating in scientific research cooperation, strengthening university-enterprise cooperation, promoting the application of research results, promoting open science and encouraging open access.

Objective To investigate the effects of L-carnitine on myocardial enzymes in infants with congenital heart disease undergoing open cardiac operation with cardio pulmonary bypass (CPB).Methods From Mar.2011 to Nov.2012,there were 60 infants with ventricular septal defects,whom were divided randomly into the test (n =30) and control (n =30) groups.L-carnitine was put in the cold crystal cardiac arresting liquid in the test group (6 g/L),other experimental conditions were the same between two groups.Before CPB,at 1 h,24 h,7 d after the pump-off,venous blood was drawn to test the level of serum creatine kinase (CK),CK-MB isozyme,cardiac Troponin I (cTnI).Blood samples were taken at different time points for the analysis of tlymphocyte and its subtype by flow cytometry.Observing the dopamine and other vasoactive drug 8 hours and 24 hours after the pump-off,using data obtained from the t-test done statistically.Results The levels of CK and CK-MB and cTnI had no difference between two groups before operation.From the end of CPB,the levels of CK and CK-MB and cTnI were significantly lower in the test group than that in the control group (P ＜0.05).The automatic jump higher rate (95％ vs 70％,P ＜ 0.05) and the amount of dopamine were significantly less than the control group (P ＜ 0.05).Conclusions L-carnitine improved obviously microcirculation of ischemic cardiac reperfusion injury undergoing open cardiac operation under CPB and heart function.It had a good protective effect on myocardium in infants.

AIM:To investigate the expression and function of store-operated calcium channels ( SOCC) in human circulating fibrocytes.METHODS:Peripheral blood mononuclear cells ( PBMCs) were isolated and cultured in ser-um-free media.After 7 d, the PBMCs differentiated into fibrocytes.RT-PCR and real-time PCR were performed to deter-mine the mRNA expression of ORAI1-3 and STIM1-2 in the fibrocytes.SOCC inhibitor SKF-96365 was used to elucidate the role of SOCC in the differentiation of fibrocytes.RESULTS:The results of real-time PCR showed that the mRNA ex-pression of ORAI1-3 and STIM1-2 was positive in cultured fibrocytes.SKF-96365 (10μmol/L) significantly inhibited the differentiation of fibrocytes.CONCLUSION:SOCC-related proteins ORAI1-3 and STIM1-2 are abundantly expressed in the fibrocytes, and may play an important role in the differentiation of these cells.

Objective:This study examined the associations between the levels of bile acids in early pregnancy and the occurrence of overweight.Methods:From 2010 to 2012, 22 302 pregnant women were recruited by Tianjin Women and Children′s Health Center to investigate gestational diabetes. Two hundred and forty-three women with gestational diabetes mellitus provided overnight fasting blood samples in the first trimester, and 243 counterparts without gestational diabetes mellitus matched on age were selected randomly to establish a nested case-control study. The association between bile acids and overweight were evaluated by binary logistic regression with data from 166 overweight pregnant women (body mass index≥24.0 kg/m 2) and 320 normal weight subjects (body mass index <24.0 kg/m 2). Results:Compared to non-overweight group, the level of primary unconjugated bile acids in overweight group was significantly higher. After adjustment of confounding factors, the OR of cholic acid (CA)>0.086 nmol/mL for overweight was 2.09 (95% CI 1.14-3.80, adjusted P=0.040), and OR of chenodeoxycholic acid (CDCA)>0.043 nmol/mL was 2.15 (95% CI 1.22-3.78, adjusted P=0.040) compared with the lower groups. However, the significant associations between the other bile acids and overweight were not detected. Stepwise selection was used to identify significant bile acid species in logistic regression. We found that only CA was independently associated with overweight, and the OR of CA>0.086 nmol/mL vs≤0.086 nmol/mL was 2.03 (95% CI 1.11-3.74, P=0.022). Conclusion:CA and CDCA in early pregnancy maybe associated with overweight, and CA might be independently associated with overweight.

Objective:To explore the clinical application value of sentinel lymph node biopsy (SLNB) in patients with early breast cancer after local excision surgery.Methods:A total of 93 breast cancer patients with clinical stage T is/T 1-2N 0M 0 who underwent SLNB and were confirmed by using tumor mass excision biopsy from March 2012 to November 2018 in Shanxi Bethune Hospital were retrospectively analyzed. According to the postoperative paraffin pathology, the patients who were successfully detected sentinel lymph node (SLN) were divided into SLN-positive group with metastasis or SLN-negative group without metastasis. The clinicopathological data were used to analyze influencing factors of SLN metastasis and SLN detection number after excision biopsy of breast masses in the two groups. Results:A total of 87 out of 93 patients were successfully detected SLN and the detection rate was 93.5% (87/93). A total of 255 SLN were detected, and the average number was 2.93 in per patient. All were subjected to rapid intraoperative freezing pathological, and 11 cases with positive SLN were detected. There were 17 patients who underwent axillary lymph node dissection (ALND), including 11 cases with positive SLN and 6 cases with SLN undetected. The paraffin pathology showed that 14 patients were confirmed as positive SLN, including 13 macrometastasis and 1 micrometastasis. The SLN false negative rate was 2.1% (3/14) of intraoperative frozen diagnosis. Univariate analysis showed that histological grade and intravascular thrombus of carcinoma were associated with SLN metastasis after breast cancer local excision; the number of SLN detection was effected by body mass index and staining method; the methylene staining method combined with radionuclide method could improve the detection rate of SLN (all P < 0.05). Multivariate analysis showed that the SLN non-detection of obesity patients was 2.651 times as much as that of normal patients (95% CI 1.592-8.194, P=0.010). Conclusion:The SLNB and appropriate tracer method will have a high SLN detection rate and better clinical application value for early breast cancer patients after breast mass resection.

Objective: To investigate the relationship between breast cancer and thyroid cancer. Methods: A cohort of 747 female patients with stage Ⅰ-Ⅲ invasive breast cancer were enrolled in this retrospective study. The differences of clinical and pathological data were compared between the simple breast cancer group (723 cases) and the breast cancer with thyroid cancer group (24 cases), to analyze the relevant factors of second primary thyroid cancer in patients with breast cancer. Results: There were significant differences in the menstrual status and estrogen receptor (ER) status between the group of patients with breast cancer only and breast cancer patients with secondary primary thyroid cancer (P<0.05). Breast cancer patients with secondary primary thyroid cancer were more likely to be premenopausal (75%) and ER-positive (83.3%). Multivariate logistic regression analysis showed that the patient′s menstrual status (compared with premenopausal patients, peri-menopausal odds ratio=0.53, 95% CI 0.07-4.25; post-menopausal odds ration=0.23, 95%CI 0.08-0.65) and body mass index (BMI, odds ratio=1.14, 95%CI 1.02-1.28) were independent risk factors for secondary primary thyroid cancer in patients with breast cancer. Conclusion Thyroid cancer is associated with breast cancer, and is more likely to occur in obesity patients and premenopausal patients.