Diabetes Mellitus, Type 2 ; complications ; Humans ; Non-alcoholic Fatty Liver Disease ; complications

Objective:To compare the dissolution results of doxazosin mesylate extended release tablets determined by a fiber-optic method and the imported drug registration standard method. Methods:The drug release process was determined directly with a FODT-601 fiber-optic medicine dissolution/ release rate process monitoring system. Aqueous solution of hydrochloric acid and sodium chloride was used as the dissolution medium, the paddle rotation rate was 75 r·min-1 , the detection wavelength was set at 246 nm while the reference wavelength was 550 nm. The detection length was 5 mm. Results:The standard curve of doxazosin mesylate was linear within the concentration range of 0. 468 1-11. 700 0μg·ml-1 and r values were greater than 0. 999 0. The intra-and inter-day RSD (n=6) was 1. 6% and 2. 0%, respectively. The recovery of doxazosin mesylate was 99. 0% and RSD was 1. 4(n=9). The results determined by the fiber-optic method were generally higher than those determined by the standard method, and there were some differences in the measurement results. Conclusion:Fiber-optic method shows the whole dissolution process objectively. It is particularly prominent in the research on the dissolution of rapid, extended and controlled release preparations. However, it can not replace the standard method yet.

Biochemical markers of bone metabolism are some of the final product which are released into the blood during the process of bone resorption or bone formation.Accumulative evidence shows that biochemical markers of bone metabolism through enzyme-linked immunoassay (ELISA) are more sensitive and specific than imaging examination.Moreover,biochemical markers of bone metabolism also display their superiorities on the early diagonosis,monitoring efficacy and prognosis evaluation in patients with bone metastases.Applications of biochemical markers of bone metabolism combined with imaging examination are more value for the early diagonosis,monitoring efficacy and prognosis evaluation in patients with bone metastases.

Objective To study the effect of Toll-like receptor 4(TLR4)on the expression of IRF-3 and IFN-β during the inflammatory reaction induced by cerebral ischemia reperfusion in mice.Methods Totally 144 mice were randomly divided into 3 groups:(1)ischemia reperfusion group(I group):the mice were subjected to 12 minutes ischemia by bilateral common carotid arteries(CCA)occlusion,and reperfusion without additional intervention;(2)TLR4 blocking group(T group):after 10 minutes of bilateral CCA occlusion,TLR4 antibody was injected slowly into right CCA within 2 minutes;(3)sham group(S group):no CCA occlusion was performed.At 1,2,3 and 4 d after ischemia reperfusion,the expression levels of TLR4,IRF-3 and IFN-β protein in the cortex was respectively examined by Western blot.Results In the right cortex,the expression levels of TLR4,IRF-3 and IFN-β of I group were distinctly higher than that of S and T gtoup(P<0.05);the expression levels of the 3 protein of T group were significantly higher than those of S group(P<0.05).Conclusion The cerebral ischemia reperfusion could activate TLR4 expression in the cortex of the mice.TLR4 might participate in the cerebral ischemia reperfusion through upregulating the expression of IRF-3 and IFN-β.

BACKGROUND:Overweight and obesity can lead to a disorder of sex hormone in men. The increase in female hormone levels may inhibit the synthesis and secretion of male hormone, increase fat accumulation and form a vicious circle. Exercise can effectively reduce body fat. OBJECTIVE: To investigate the effects of different exercise loads on sex hormone and the quality of sperm in obese male mice. METHODS: Weanling male C57BL/6J mice were divided into normal control group and obesity group. Mice in the obesity group were given high fat diet for 10 weeks to establish mouse model of obesity. The amount of food and water was recorded daily. Body weight was weighed once every week. After model induction, models were assigned to obesity moderate load exercise group and obesity high load exercise group. These models did exercises for 8 weeks. Body length was measured. Body weight, abdominal fat, testis, epididymis and seminal vesicle were weighed. Sperm activity and motility were observed by the sperm counting method in the epididymis tail. Enzyme linked immunosorbent assay was used to measure serum progesterone, folicle stimulating hormone, testosterone and estradiol. RESULTS AND CONCLUSION:Compared with the normal control group, body weight, abdominal fat weight, and lee’s index were increased (P < 0.01); the coefficient of testis and seminal vesicle were significantly decreased (P < 0.01); serum levels of luteinizing hormone, folicle stimulating hormone and testosterone were significantly decreased and estradiol level was significantly increased (P< 0.05); sperm count and activity were significantly decreased in the obesity group (P < 0.01). Compared with the obesity group, body weight, abdominal fat weight and lee’s index were significantly decreased (P < 0.05 orP < 0.01); the coefficient of testis and seminal vesicle were significantly increased in the obesity moderate load exercise group and obesity high load exercise group (P < 0.05 orP < 0.01). Serum luteinizing hormone, folicle stimulating hormone and testosterone levels were significantly increased (P < 0.05 orP < 0.01); estradiol levels were significantly decreased (P < 0.05); sperm count and activity were significantly increased (P < 0.01,P < 0.05) in the obesity moderate load exercise group. Compared with the obesity moderate load exercise group, abdominal fat weight and lee’s index were significantly reduced (P < 0.05); serum luteinizing hormone, folicle stimulating hormone, testosterone, sperm count and activity were decreased in the obesity high load exercise group (P < 0.01). These results indicate that long-term high fat diet leads to early obesity in males, inhibits the development of the reproductive gland and reproductive organs, and causes the decrease of the level of male hormone and sperm quality. Long-term moderate load exercise effectively reduces body fat, improves the inhibitory effect on male reproductive organs and glands, and relieves the negative effect of obesity on reproductive function. The effect of long-term large load exercise on reducing body fat is better than medium load exercise, but it has little effect on improving the level of male hormone in obese mice or on relieving the negative effect of obesity on reproductive function, even has a tendency to aggravate.

Bone-modifying agents (BMA) is a series drugs to alleviate the pain,pathological fractures,spinal cord compression,hypercalcemia,bone-related events which induced by bone metastases.Bisphosphonate drugs and denosumab are two dominant kinds of BMA at present.It has been proved that BMA is used in bone metastases patients with bone destruction,as adjuvant therapy for chemotherapy and radiotherapy,which can significantly improve the efficacy and prolong the survival of patients.In addition,some traditional Chinese medcine can effectively relieve a series of related symptoms caused by bone metastases and improve prognosis.Choosing right medication in clinical work can maximize the reduction of pain caused by bonerelated events and improve the quality of life of patients.

Objective To explore the radiosensitizatian of paclitaxel in human lung adenocareinoma cells. Methods A human lung adenocarcinoma cell line A973 was used in this study. The cytotoxicity of paclitaxel was investigated by using clonngenic assay to define the IC10,IC50 and IC90. The cells received either radiation(with different doses) alone or paclitaxel administrated before and after irradiation. Cell survival fractions were determined by clonogenic assay. Single hit multi-target model was used to determine survival curve parameters. Flow cytometry was performed to analyze the cell cycle distribution. Results The IC10, IC50 and IC90 of paclitaxel in A973 cells were 0.5,2.6 and 8.7 nmol/L,respectively. According to Do,Dq and SF2 value,the sensitivity enhancement ratio(SER) of IC10 was 0.97,1.01 and 2.00 when paclitaxel was added before irradiation, and 0.97,1.02 and 1.02 when after irradiation ; The SER of IC50 was 1.06,129.00 and 2.61 when paclitaxel was added before irradiation, and 0.94,220. O0 and 2.14 when after irradiation ;The SER of IC90 were 1.00,220. 00 and 2.09 when paclitaxel was added before irradiation,and 0.98,220.00 and 2.09 when after irradiation. The IC10 of paclitaxei failed to increase G2+M arrest of A973 cells.The maximal G2+M accumulation was reached at 2 h and 18 h after IC50 and IC90 of paclitaxel treatment,respectively. Conclusions Paclitaxel is able to enhance the radiation sensitivity of A973 cells. Sequence of treatment is not associated with radiosensitivity. Moderate and high dose of paclitaxel combined with low-dose radiation can produce the best effect of radiosensitiation.

The lymphatic metastasis affects prognosis and survival of colorectal cancer seriously,and lymphangiogenesis plays an important role in the lymphatic metastasis. Many factors such as COX-2 and MMP-7 which are found in many researches recently can promote the expression of VEGF-C which can promote the lym-phangiogenesis by connecting with its receptor and activating the relevant signal pathway. At present,as these related factors of lymphangiogenesis are found in colorectal cancer,the process of lymphangiogenesis in colorec-tal cancer becomes more clear,but the exact mechanism of these factors needs to be researched in future.

Objective To evaluate the preclinical safety of 2-methoxyestradiol nanosuspension. Methods The safety of 2-methoxyestradiol nanosuspension for injection was observed through vascular stimulation test of the ear vein on rabbits, hemolytic test using rabbit erythrocytes, active systemic anaphylaxis (ASA) test on guinea pigs and acute toxicity test on mice. Results 2-Methoxyestradiol nanosuspension injection had no irritating effects on vessels, and no haemocytolysis, agglutination and ASA occurred.ASA test showed no allergy symptoms such as piloerection, nose rubbing and dyspnea in guinea pigs 30 min after sensitization.Acute toxicity test revealed that no pathological changes, including black spots and hyperaemia, were visually observed on the heart, liver and lungs after 14 days of intravenous administration. Conclusion 2-Methoxyestradiol nanosuspension injection is relatively safe, with low toxicity, and no hemolytic, anaphylactic and irritating effects. It may be clinically used for injection.

Objective:To investigate the effect of compound Sanggou granules on the activity of Fib, AT-Ⅲ, t-PA, PAI-1 and t-PA/ PAI-1 in hyperlipidemic rats. Methods: The hyperlipidemic rat model was established by feeding high fat diet to SD male rats. Sixty healthy SD rats were randomly divided into five groups: the normal diet control group, high fat control group, high dose drug group, low dose drug group and fluvastatin sodium group. Four weeks after the administration, the blood samples were withdrawn for the determination of the levels of blood lipid, Fib, A-Ⅲ, t-PA, PAI-1 and t-PA/ PAI-1. Results:Compared with those of the normal diet control group, the levels of TC, LDL-C, Fib and PAI-1 were increased and the levels of HDL-C, t-PA , AT-Ⅲand t-PA/ PAI-1 were decreased significantly (P<0. 01) in the high fat control group. Compared with those of the high fat control group, the levels of TC, LDL-C, PAI-1 and Fib were decreased(P<0. 01 or P<0. 05),and the levels of HDL-C, t-PA AT-Ⅲ and t-PA/PAI-1 were in-creased significantly in the high dose drug group (P<0. 05 or P<0. 01). The similar effects were shown in the fluvastatin sodium group with the stability of AT-Ⅲ. The levels of TC, LDL-C and PAI-1 were decreased and the levels of t-PA/PAI-1 were increased no-tably in the low dose drug group. Conclusion: Compound Sanggou granules exhibit hypolipidemic effect in hyperlipidemic rats, and can improve hypercoagulability and enhance anticoagulation and fibrinolytic activity in hyperlipidemic rats. Furthermore, compound Sanggou granules at high dose show the same effect as fluvastatin sodium, even in anticoagulation, the granules are superior to fluvasta-tin sodium.