Objective To investigate the effect of propofol on nNOS expression after focal cerebral ischemia-reperfusion in rats and the possible mechanism of protective effect of propofol on brain. Method Seventy-eight male Wistar rats, weighting 250 ~ 300 g, were randomly divided into 3 groups:(1)Sham operation group (S group, n=6) was performed with scham operation; (2) Ischemia-reperfusion group (group I-R, n=36) was subjected to 2-hour right middle cerebral artery occlusion and then reperfusion was followed, saline (1 mg/kg) was injected into the right lateral cerebral ventricle using microsyringe before reperfusion;(3) Propefol group (group P, n=36) was injected with propofol (1mg/kg) into the right lateral cerebral ventricle using microsyringe right after ischemia. Group I-R and group P were divided into 3 subgroups according to the reperfusion time: 1 h, 3 h and 6 h. The neurological function of all rats were tested before reperfusion. The cerebral infarction area of the whole brain was calculated with TIC staining (n=6). The pathological change of brain was observed from HE staining (n=6) and the nNOS protein expression was obtained by immuno- histochemical method (n=6). Results Compared with I-R group, the neurological function was better in group P(P

The COVID-19 outbreak has drawn attention to viral infectious diseases once again, and the development of antiviral drugs for both known and potentially emerging viruses is of great significance. In recent years, peptides and protein drugs are becoming a hot spot in the field of antiviral drug research and development. Phage display technology, as a powerful tool for screening peptides and protein drugs, has been increasingly concerned in the academic and industrial fields. The present review introduced the basic principle of phage display technology, summarized phage display libraries often used in antiviral drug discovery and their applications, discussed the challenges and future direction of antiviral drug research and development based on phage display technology.

Objective To evaluate the feasibility of making the osteoarthritis (OA) model in the medial collateral ligament and the medial meniscus excision in rats,and to explore the mechanism of MMP-13 and ADAMTS-5 protein in the cartilage of rat osteoarthritis models.Methods Forty SD rats were randomly divided into model group(n =30) and sham operation group(n =10).The knee joint OA model was made from the medial collateral ligament of the knee and the medial meniscus,and the sham operation group was sutured after opening the capsule of the knee joint.Rats in the model group were killed at 4,6,and 8 weeks after the operation,and the sham operation group died of the rats at 8 weeks after the operation.The articular cartilage tissue of rats was taken.The expression level of MMP-13 and ADAMTS-5 protein in cartilage tissue was detected by Western blot and immunohistochemistry.Results Cartilage degeneration was observed in the model group 4 weeks after operation,and degeneration was further aggravated at 6 and 8 weeks.There was no significant degeneration in the sham operation group.There was a significant difference in the articular cartilage score between the two groups (P ＜ 0.05).The results of Western blot detection showed that the protein expression of MMP-13 and ADAMTS-5 was low in the sham operation group.The MMP-13 model began to rise for 4 weeks,and continued to rise in the 6th week,and the 8th week was lower than that of the previous one.The protein expression had significant difference in all groups at 4 weeks,6 weeks and 8 weeks (P ＜ 0.05).The ADAMTS-5 model began to rise for 6 weeks,and the expression level was maintained before the model was maintained for 8 weeks.The protein expression at 4 weeks compared to that at 6 weeks and 8 weeks had significant difference(P ＜0.05).The protein expression in rat articular cartilage tissue at 6 weeks and 8 weeks had no significant difference (P ＞ 0.05).The expression trend of immunohistochemical detection protein was consistent with that of Western blot.Conclusion The animal model of OA can be established by using the method of medial collateral ligament dissection and medial meniscectomy.The expression level of MMP-13 and ADAMTS-5 in different stages of OA has changed significantly.Further research is needed to explore its related signaling pathways.

Objective To investigate the effects of a novel enhancer of Zeste homolog 2 (EZH2) inhibitor GSK126 in vitro on the cell proliferation and apoptosis in acute leukemia and lymphoma cells. Methods CCKˉ8 assay was used to measure the effects of GSK126 with different concentrations and time on the cell proliferation in human Tˉcell acute lymphoblastic leukemia (TˉALL) CEM cell line, acute monocytic leukemia U937 cell line and Burkitt lymphoma Raji cell line. Annexin V/PI double staining method was used to determine the effects of GSK126 on the cell apoptosis. The effect of GSK126 on the mRNA levels of EZH2, bclˉ2 and bclˉxL were measured by using quantitative polymerase chain reaction (qPCR). Results After the function for 24 h, 48 h and 72 h, compared to the negative control group (0 μmol/L), 5, 10, 15, 20, 25 μmol/L GSK126 treatment showed a significant doseˉand timeˉdependent cell proliferation suppression in CEM cells; 5, 10, 15, 20 μmol/L GSK126 treatment showed a significant doseˉand timeˉdependent cell proliferation suppression in U937 cells; 5, 10, 15, 20, 25, 30 μmol/L GSK126 treatment showed a significant timeˉdependent suppression in Raji cells (all P< 0.05). The 48 h 50% inhibitory concentration ( IC 50) of GSK126 on CEM, U937, Raji cells was (13.46 ±0.83), (11.65 ±1.02), (15.00 ±0.19) μmol/L, respectively. GSK126 treatment with the doses of 8, 12 and 16 μmol/L promoted the apoptosis of CEM and U937 cells compared with the negative control group (0 μmol/L), and there were statistical differences in the apoptosis rate (F＝ 167.995, P< 0.01; F＝ 158.400, P< 0.01). In Raji cells, only 16 μmol/L GSK126 treatment had a higher cell apoptosis rate compared with the control group (t＝ 47.998, P< 0.05). Furthermore, 8, 12 and 16 μmol/L GSK126 treatment suppressed the expressions of EZH2 mRNA in CEM, U937 and Raji cells compared with the control group (F＝82.035, P<0.01; F＝ 252.712, P< 0.01; F＝ 690.536, P< 0.01), and the expressions of bclˉ2 and bclˉxL mRNA (bclˉ2: F＝ 1 900.525, P< 0.01; F＝ 431.324, P< 0.01; F＝216.184, P<0.01; bclˉxL: F＝256.751, P<0.01; F＝147.019, P<0.01; F＝209.325, P<0.01). Conclusion EZH2 plays an important role in the occurrence and development of acute leukemia and lymphoma. GSK126 as a high selective inhibitor of EZH2 might be a potential new drug in treatment of hematological malignancies.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

BACKGROUNDThe aim of this study was to assess the performance of apparent diffusion coefficient (ADC) measurement obtained with diffusion-weighted magnetic resonance imaging (DW-MRI) to distinguish renal cell carcinomas (RCCs) from small benign solid renal tumors (≤ 4 cm).

METHODSIn this cross-sectional study, 49 consecutive patients with histopathologically confirmed small solid renal tumors, and seven healthy volunteers were imaged using nonenhanced MRI and DW-MRI. The ADC map was calculated using the b values of 0, 50, 400, and 600 s/mm 2 and values compared via the Kruskal-Wallis and Mann-Whitney tests. The utility of ADC for differentiating RCCs and benign lesions was assessed using a receiver operating characteristic curve. Multiple nonenhanced MRI features were analyzed by Logistic regression.

RESULTSThe tumors consisted of 33 cases of clear-cell RCCs (ccRCCs) and 16 cases of benign tumors, including 14 cases of minimal fat angiomyolipomas and 2 cases of oncocytomas. The ADCs showed significant differences among benign tumors ([0.90 ± 0.52] × 10-3 mm 2 /s), ccRCCs ([1.53 ± 0.31] × 10-3 mm 2 /s) and the normal renal parenchyma ([2.22 ± 0.12] × 10-3 mm 2 /s) (P < 0.001). Moreover, there was statistically significant difference between high and low-grade ccRCCs (P = 0.004). Using a cut-off ADC of 1.36 × 10-3 mm 2 /s, DW-MRI resulted in an area under the curve (AUC), sensitivity, and specificity equal to 0.839, 75.8%, and 87.5%, respectively. Nonenhanced MRI alone and the combination of imaging methods led to an AUC, sensitivity and specificity equal to 0.919, 93.9%, and 81.2%, 0.998, 97%, and 100%, respectively. The Logistic regression showed that the location of the center of the tumor (inside the contour of the kidney) and appearance of stiff blood vessel were significantly helpful for diagnosing ccRCCs.

CONCLUSIONSDW-MRI has potential in distinguishing ccRCCs from benign lesions in human small solid renal tumors (≤ 4 cm), and in increasing the accuracy for diagnosing ccRCCs when combined with nonenhanced MRI.

Adult ; Aged ; Carcinoma, Renal Cell ; diagnosis ; Cross-Sectional Studies ; Diffusion Magnetic Resonance Imaging ; methods ; Female ; Humans ; Kidney Neoplasms ; diagnosis ; Male ; Middle Aged ; Young Adult

OBJECTIVETo estimate the association between overweight, obesity and the risk of breast cancer in Chinese female population.

METHODSLiteratures published in China and abroad about overweight, obesity and breast cancer risk among Chinese females were searched. We used "breast cancer", "overweight", "obesity", "weight", "body mass index" and "risk factors" as keywords, to retrieve papers in Chinese literature databases including CNKI, Wanfang and Weipu database. The same strategy was used to retrieve English papers in English literature database including Embase database, PubMed, Science Direct, Elsevier and Cochrane database, supplemented by literature tracing method. Time range was from the founding of each database to April 2012. A total of 124 research papers were collected. Using Stata11.2 software, meta-analysis was conducted, combined odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the associations between overweight, obesity and the risk of breast cancer in Chinese female population.

RESULTSEighteen studies were included in meta-analysis, among them 12 studies were in Chinese and 6 were in English, with a number of 7217 cases and 81 605 controls. Results showed a 7.7% increased risk of breast cancer among overweight or obesity women (OR = 1.08, 95%CI: 1.04 - 1.12). Compared with normal BMI women, the OR (95%CI) of overweight or obesity women were 1.07 (1.03 - 1.11) and 1.56 (1.29 - 1.84) before and after the adjustment of menopausal status.

CONCLUSIONOverweight, obesity may be important risk factors of breast cancer in Chinese female population. The intervention and control activities may reduce the risk of breast cancer at population level.

Asian Continental Ancestry Group ; Breast Neoplasms ; epidemiology ; China ; epidemiology ; Female ; Humans ; Obesity ; epidemiology ; Overweight ; epidemiology ; Risk Factors

OBJECTIVETo study the impact of TNM staging and combined treatment mode on the survival of non-small cell lung cancer (NSCLC) patients.

METHODSFrom January 1997 to December 2002, 987 NSCLC patients were surgically treated in this hospital. Of those, 574 received combined modality therapy (surgery + chemotherapy/radiotherapy), while 413 underwent operation alone. Their clinicopathological data were retrospectively analyzed.

RESULTSThe 1-, 3-, 5-, and 10-year overall survival rates were 87.7%, 57.5%, 54.6% and 54.5%, respectively, for the whole group, which were 90.6%, 57.5%, 54.3% and 54.1% for the combined therapy group versus 83.8%, 57.6%, 55.2% and 55.2% for the group treated by surgical resection alone. The 1-year survival rate of the combined therapy group was significantly higher than that of the surgical resection alone group (90.6% vs. 83.8%) (P<0.01). With regard to the T factor, 5-year survival rate of the combined therapy group (surgery + radiotherapy) was higher than that of surgery alone group, especially in T4 cases (43.6% vs. 12.7%), with a significant difference between them (P<0. 05). As for the N factor, the 1-year survival rate of NO patients in the combined therapy group (surgery + chemotherapy/radiotherapy) was significantly higher than that of surgery alone group (94.4%, 97.9% vs. 90.0%) (P<0.05). The 1-year survival rate of N1 patients in the combined therapy group (surgery + chemotherapy or + chemotherapy and radiotherapy) was 91.7% and 100% versus 82.9% in the surgery alone group (P<0.01); The 1- and 3-year survival rates of N2 patients in the combined modality therapy group (surgery + chemotherapy) were 82.1% and 37.3%, while those of the surgery alone group were 69.4% and 26.5%, respectively, with a significant difference (P<0.05, P<0.01). All the severity of primary tumor, distance of lymph node involvement, and distant tumor metastasis significantly worsen the prognosis of the patients.

CONCLUSIONThe prognosis in NSCLC patients treated with combined modality therapy (surgery + chemotherapy/radiotherapy) is better than that with surgery alone. The larger the original tumor and the farther the lymph node and tumor metastases, the worse the prognosis is for NSCLC patients.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; pathology ; therapy ; Chemotherapy, Adjuvant ; Child ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; pathology ; therapy ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Pneumonectomy ; methods ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Young Adult

BACKGROUND AND OBJECTIVEPatients with clinical stage I seminoma accounts for 70%-80% of patients with this disease. This study was to analyze the relationship between different therapeutic methods and the prognosis of this disease.

METHODSThe data of all patients with clinical Stage I seminoma treated by multi-disciplinary approach from 1999 to 2008 in Sun Yat-sen University Cancer Center were analyzed. The patients were divided into 3 groups based on the treatment they received after orchiectomy: 30 patients treated with chemotherapy, 8 with radiotherapy, and 20 under surveillance. The prognosis of different treatment groups was evaluated.

RESULTSAmong the 58 patients with stage I seminoma, 57 were followed up successfully. The median follow-up time was 50 months (range, 8-115 months). No relapse or metastasis was seen in the chemotherapy group. One patient relapsed in the radiotherapy group. Four patients had metastasis of retroperitoneal lymph node in the surveillance group. The disease-free survival was higher in the chemotherapy group than that in the surveillance group (P=0.005). There was no significant difference in the relapse-free survival between the surveillance group and the radiotherapy group (P=0.364).

CONCLUSIONSChemotherapy is a safe and effective treatment for patients with Stage-1 seminoma after radical orchidectomy.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; therapeutic use ; Cisplatin ; therapeutic use ; Combined Modality Therapy ; Disease-Free Survival ; Etoposide ; therapeutic use ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Orchiectomy ; methods ; Retrospective Studies ; Seminoma ; drug therapy ; pathology ; radiotherapy ; surgery ; Testicular Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Treatment Outcome ; Young Adult