OBJECTIVE: To examine and determine the contents of endothelin (ET) and nitric oxide (NO) in plasma, and to observe the effects of gastrodin injection on blood pressure, ET and NO levels in old patients with refractory hypertension. METHODS: A total of 63 old patients with refractory hypertension, 30 patients with common hypertension and 30 healthy people were included. The contents of ET and NO in plasma of patients in different groups and healthy people were examined and analyzed. The old patients with refractory hypertension were randomly divided into two groups: gastrodin-treated and routine treatment groups. Besides conventional hypotensive drugs, intravenous drip infusion of 1 000 mg gastrodin was administered to the patients in gastrodin-treated group for two courses (4 weeks), while the patients in routine treatment group were treated only with conventional hypotensive drugs. The changes of blood pressure, ET and NO levels before and after treatment in different groups were measured. RESULTS: The plasma level of ET in refractory hypertension group was higher than that in common hypertension group (t=3.27, P=0.008), while the level of NO was lower (t=-3.81, P=0.002). The systolic pressure and pulse pressure difference in gastrodin-treated group were decreased significantly after one course of treatment (t=1.85, P=0.03; t=1.74, P=0.04). The level of ET in gastrodin-treated group decreased gradually after treatment, but there were no significant difference between before treatment and two courses of treatment, while the level of NO in gastrodin-treated group was increased after treatment (t=-2.70; P=0.04). CONCLUSION: Gastrodin injection is beneficial to old patients with refractory hypertension, and can improve the balance of ET and NO levels in plasma.

Objective: To select suitable conditions for prokaryotic expression and purification of rhIL-17. Methods: rhIL-17 was expressed in E. coli host under heat induction. After compared among the expression amounts in different media under different heat induction time, the most suitable conditions was selected. The target protein was present in the form of inclusion body. The precipitate of inclusion was obtained and purified after 6M guanidine solublization or 2% SDS solublization. Results: Either protocol could yield rhIL-17 with high purity and stable activity. The SDS solublization mehthod gives rise to much more higher productivity than the guanidine solublization method. Conclusion: rhIL-17 were expression in E. coli system and purified to homogenicity by SDS solublization methods with high productivity.

Objective To investigate the expression of PTTG and VEGF-C in laryngeal carcinoma and the effect of angiogene-sis .Methods Immunohistochemistry was used to detect the expression of PTTG 、VEGF-C and LMVD in 60 cases of laryngeal car-cinoma and 32 cases of para-carcinoma tissue .D2 40 positive products was used to locate lymphatic endothelial cell cytoplasm and cell membrane ,and count lymphatic microvessel density (LMVD) .Results The expression of PTTG and VEGF-C in laryngeal car-cinoma was significantly higher than that in para-carcinoma tissue(P<0 .05) .In laryngeal carcinoma ,the expression of PTTG and VEGF-C were associated with differentiation ,lymph node metastasis and clinical stage(P<0 .05) ,but independent of clinical classi-fication ,smoking history ,tumor′size ,sex and gender(P>0 .05) .The expression of LMVD in laryngeal carcinoma was significantly higher than that in para-carcinoma tissue(P<0 .05) .The expression of LMVD was associated with lymph node metastasis (P<0 .05) ,but independent of differentiation ,clinical classification ,clinical stage smoking history ,tumor′size ,sex and gender ( P>0 .05) .A significantly positive relation was found between PTTG and VEGF-C(P<0 .05) .And there were positive relation between PTTG and LMVD、VEGF-C and LMVD(P<0 .05) .Conclusion PTTG and VEGF-C might play an important role in the carcino-genesis and development of laryngeal carcinoma .PTTG and VEGF-C could be a prognostic factor of colorectal cancer and a new tar-get of gene therapy .

Objective To develop a subgroup analysis method that can simultaneously deal with longitudinal data containing measurement errors and dropouts.Methods Subgroup analysis was carried out based on a threshold regression model.A new generalized unbiased estimation equation is constructed by using the independence between repeated measurements to deal with measurement errors and introducing an inverse probability weighting matrix to deal with missing response.Results The computer stochastic simulation shows that the proposed estimation method is effective in dealing with measurement errors and dropouts,and has smaller bias and mean square error than the generalized estimation equation method without correcting measurement errors or dropouts.Conclusion In subgroup analysis,when there are measurement errors in covariables and missing values in response variables,it is usually necessary to deal with the measurement errors and missing values in order to obtain reliable parameter estimation.

Objective To evaluate the association between birth weight and subsequent risk of type 2 diabetes (T2DM) across two generations in Chinese females.Methods A cross-sectional survey was conducted among 10 324 blood-related females in Shanghai from November 2012 to January 2013.A structured questionnaire was used to collect data about demographic information,birth weight,lifestyle factors and diagnosis of T2DM.Path analysis was performed to estimate the matemal effect of birth weight and diabetes status on their offspring,and mediation analysis was conducted to test whether birth weight mediates the association between maternal and daughters' diabetes status.Results A positive association was observed between maternal and daughters' birth weight.One kg increase in maternal birth weight was associated with an average of 0.335 (95％CI:0.307-0.363) kg elevated birth weight in female offspring.Maternal diabetes status was also related with an average of 0.066 (95％ CI:0.025-0.107) kg increase in birth weight and tripled risk of subsequent T2DM (OR=3.173,95％CI:1.946-5.174) in female offspring.In all subjects aged ≥20 years,no significant relationship was observed between birth weight and risk of T2DM subsequently after adjusting for age.Offspring' s birth weight,as a mediator of maternal and daughters' diabetes status,explained 2.8％ of their association.Conclusion Maternal birth weight and diabetes status may influence their female offspring' s birth weight and subsequent risk of T2DM.

N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m⁶A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.