Objective To observe the changes of type 2 diabetes mellitus patients in blood sugar,TC,TG,HDL C,plasma insulin,body mass index(BMI), microalbuminuria,etc before and after moderate intensity exercise training.Methods 28 patients with mean age of 59.0?7.6 years did moderate intensity exercise training for 1～1.5 hours every day for 12 month.At the same time they received the treatment of diet and oral antidiabetic drug com pared with 40 controls without exercise training. Before and after the observing period we measured the values of items above.Results Plasma glucose level , HbAlc,AUCGS(the area under the curve of glucose sugar) and BMI in fat diabetes with training team were obviously decreased compared with those before observation( P 0.05).Conclusion Exercise training can significantly descend blood sugar, insulin resistance and BMI of obese people ,improve lipidmetabolism and ascend insulin sensitivity. So the action of exercise can't be replaced by the diet and oral drug.

Objective To investigate the possibility of differentiation of multipotent adult progenitor cells from human bone marrow(hMAPCs) into hepatocytes with hepatocyte growth factor (HGF) and fibroblast growth factor-4 (FGF-4) in vitro to find a new cell source for liver tissue engineering. Methods (1) Harvest of the hMAPCs: The bone marrow mononuclear cells were obtained from bone marrow obtained from volunteers by gradient centrifuging. The adherent mononuclear cells were cultured. The mesenchymal stem cells(MSCs) were isolated and collected by magnetic activated cell sorting(MACS) through depletion selection by the use of CD45 and GlyA microbeads. (2) The hMAPCs were induced to differentiate with HGF(20ng/ml) +FGF-4(10ng/ml). L-02 human hepatocytes (cell lines) were used as the control, with undifferentiated hMAPCs serving as the contrast. (3)The expression of albumin (ALB), alpha fetoprotein (AFP), cytokeratin-18(CK-18), cytokeratin-19(CK-19) was detected with immunocytochemistry to identify the characters of the differentiated cells at different time, and to determine the ratio of positive cells. (4) ALB expression of the differentiated cells at different time was detected by Western blot on day 21 and 25. Results (1) The result of immunocytochemistry: The differentiated hMAPCs expressed the late markers (ALB, CK-18) of hepatocyte at all the time but did not express CK-19. The differentiated hMAPCs expressed AFP on day 7. (2) The result of Western blot assay: the differentiated cells expressed the late markers (ALB) of hepatocyte on day 21 and 35. Conclusions hMAPCs can differentiate into hepatocyte-like cells under specific inducing conditions.

Accidents, Occupational ; Humans ; Hydrogen Sulfide ; poisoning

Objective To evaluate the security of big animals with a new bioartificial liver system .Methods Six Tibet pigs re-spectively received treatment of hybrid artificial liver and simple bioartificial liver ,observed and recorded the vital signs ,venous pressure ,transmembrane pressure and slurry pot pressure each hour ,and collected blood to make endotoxin and bacterial culture test in the zero hour ,fourth and eighth hour .Results Compared with the zero hour ,venous pressure ,transmembrane pressure ,slur-ry pot pressure were much higher in the fifth hour (P< 0 .05) ,and there were no significant difference in the rest of other time points(P>0 .05) .The mean arterial pressure and respiratory rate in all time point showed no significant changes (P>0 .05) .Com-pared with the zero hour ,the heart rate was much lower in the second hour (P<0 .01) .The values of blood endotoxin were less than 0 .5 EU/mL in the zero hour ,fourth and eighth hour from beginning ,and the bacterial culture test showed no growth of bacteria . Conclusion The experiment of big animals with a new bioartificial liver system was safe ,the efficacy in the treatment of hepatic failure could be assessed further .

Adult ; Embolism, Amniotic Fluid ; etiology ; therapy ; Female ; Humans ; Pregnancy

Nanocrystal drugs have many advantages, such as no carrier materials, easy industrialization, diversified dosage forms, and can significantly improve the solubility and bioavailability of insoluble drugs, so many drugs have been on the market. The traditional nanocrystal preparation technology has the problems of low preparation efficiency and process limitation of the smallest achievable particle size. With the progress of pharmaceutical preparation technology, the preparation technology of nanocrystal drugs is constantly improving, and new preparation technologies are constantly emerging. The emergence of new technologies has greatly shortened the process time and makes it possible to prepare nanocrystal drugs with smaller particle diameters. In this paper, the preparation technologies of nanocrystal drugs, especially the new preparation technologies such as high gravity controlled precipitation, microfluidic reaction technology and various combination technologies, are reviewed from three aspects: "Top-down" technology, "Bottom-up" technology and combination technology. This article also prospects the development of new preparation technologies, hoping to provide reference for the related research of nano-preparations.

Objective To investigate the expression of extraeellular signal-regulated protein kinase (ERK1/2)pathway in rat brains with fluorosis and the effects of fluoride on learning and memory of the rats,and to reveal the mechanisms of damaged nervous system resulted from the toxicity of the ion.Methods Seventy-two SD rats were divided into 3 groups and 24 rats were in each group.Three groups were fed respectively with different concentrations of fluoride(NaF)for 6 months to establish rat models with fluorosis.Controls were fed with tap water (NaF＜0.5 mg/L):lower and higher concentration group were fed with water containing NaF(5,50 ms/L).Animals are sacrificed after 6 months of treatment with fluoride and the dissected brains were kept for analysis.The protein levels of ERK1/2 in rat brains were detected by Western-blotting and the mRNA level by RT-PCR. The spatial learning and memorizing ability was measured by Morris water maze test. Results The ERK1/2 protein in control group,lower and higher concentration group was 0.944±0.10,1.253±0.02,1.953±0.07,the differece being statistieally sighificant between any two groups (P ＜ 0.05). The phospho-ERKl/2 protein in control group,lower and higher concentration group was 0.73±0.08,0.77±0.07,1.28±0.11,the differece being statistieally sighificant between any two groups(P ＜ 0.05);the activation rate of phospho-ERK1/2 in lower and higher concentration group [(68.4± 3.8)%,(64.1±3.2)%] was decreased compared to control group[ (82.3±10.7)%],the differece being significant(P ＜ 0.05). In the navigation trial,longer escape latencies of lower concentration group on the second, the third,the fifth and the sixth day were observed[ (46.0±8.0),(24.0±2.7),(8.9±5.3),(7.4±4.1 )s] compared to the control[ (39.3±6.9),(19.1±9.1 ),(8.3±3.4),(4.8±2.7)s],the differece being significant (P ＜ 0.05 or ＜ 0.01 );the similar results were also observed in the higher concentration group[ (36.9±16.8),(37.7±12.9), (19.7±7.6),(12.2±5.7 )s],and the escape latencies of the higher concentration group on the third,the fifth and the sixth day were longer than that in lower concentration group. In the probe test,the rats took more time to reach the first cross in lower and higher concentration group[(1.17±0.75),(4.18±1.10)s] than control group[ (5.89± 0.56 ) s ],the differece being significant (P ＜ 0.05 or ＜ 0.01 ) ;stayed shorter [ ( 17.05±4.25 ),(18.20±4.57 ) s ] than control [(25.37±5.65 )s ] in platform area (P ＜ 0.01 );the activation rates of ERK1/2 were directly correlated with the time taken to reach the first cross platform located in the probe test(r = 0.364,P ＜ 0.05) and the activation rates were also directly correlated with the escape latencies on the sixth day(r = 0.497,P ＜ 0.05). Conclusion Long-term exposure of excessive fluoride induces the change of expression and activating rate of the ERK1/2 in rat brains,leading to the decreased capacity of learning and memory.

Objective To investigate the expression and distribution of the downstream substrate of extracellular regulated protein kinase(ERK1/2) pathway, ternary complex factor phospho-Elk-1, in rat brains with chronic fluorosis, and reveal the mechanism of the impaired learning and memory ability caused by chronic fluorosis. Methods Seventy-two SD rats, weighing 100 - 120 g, were randomly divided into 3 groups, 24 in each group (half male and half female). The rats in control group were fed with tap water (fluoride < 0.5 mg/L); low- and high-dose fluoride groups were fed with tap water with different concentrations of NaF(5.0,50.0 mg/L F-, respectively). After 6 months, body weight was weighed, dental fluorosis was determined by observation and urinary fluoride and bone fluoride were detected by fluorine ion-selective electrode; the learning ability of rats was measured by navigation test of Morris water maze, and memory ability by spatial probe test in Morris water maze; the expression and distribution of phospho-Elk-1 in different brain regions were detected by immunohistochemistry method. Results In low- and high-fluoride groups, the body weight of rat[(449.2 ± 77.1), (312.8 ± 89.7)g] was significantly decreased than that of control [(635.5 ± 76.2 )g, all P< 0.05], the varying degrees of dental fluorosis were observed(x2 = 7.83, P<0.05), urinary fluoride[(2.56 ±0.91),(5.73 ±3.14)mg/L] and bone fluoride[(709.2 ± 37.4) ,(1306.3 ± 102.4) mg/kg] were significantly higher than those in controls[(0.92 ± 0.30)mg/L,(348.5 ± 89.2)mg/kg, all P< 0.05]. The escape latency of low- and high-fluoride groups[ (7.4 ± 4.1), (12.2 ± 5.7)s] was longer than that of control [(4.8 ± 2.7 )s, all P < 0.05] and the escape latency in high-fluoride group was significantly longer than that in other groups (all P < 0.05); in spatial probe test, the time of first crossing platform was longer in rats with fluorosis [(4.18 ± 1.10),(5.89 ± 0.56)s] as compared to control[(1.17 ± 0.75)s, all P< 0.05]. Expressions of phospho-Elk-1 in the hippocampus CA1(167.4 ± 8.3,163.2 ± 9.4), CA2(175.7 ± 5.0,183.3 ± 4.2), CA3(165.2 ± 11.6,162.9 ± 4.4), CA4(168.7± 6.9,169.5 ±5.3), fascia dentate (185.2 ±4.0,193.1 ±6.1) and caudate putamen( 181.4 ± 3.8, 179.8 ± 5.5) in low- and high-fluoride groups were higher than those of controls(142.4 ± 8.1,144.9 ± 8.4,143.6 ± 5.8, 116.8 ± 9.1,140.2 ± 7.8,163.1 ± 13.1, all P< 0.05). Conclusion Chronic fluorosis can cause increased expression of phospho-Elk-1 in the hippocampus and caudate putamen region of rat brains, which might be related to the mechanisms of decreased learning and memory ability of rats overexposed to fluoride.

Objective To investigate the changes of oxidative stress level in brain tissues and serum, and learning and memory in rats with oxidative stress level in nerve damage in chronic fluorosis. Methods The rats were randomly divided into 3 groups according to the body weight, eight rats in each group, i.e., control group, drinking water containing less than 0.5 mg/L of fluoride; lower fluoride exposure group, drinking water containing 5 mg/L of fluoride; higher fluoride exposure group, drinking water containing 50 mg/L of fluoride. The animals were examined six months after initiating the experiment. The total antioxidant capacity (T-AOC) and malondialdehyde (MDA), as well as learning and memory, were measured. Results Escape latency in higher fluoride exposed group[ (14.37±3.48)s] was significantly higher than that of controls[ (5.84±1.87)s] and exposed te lower fluoride [ (7.18±1.42)s], the difference being statistically signifieant(P<0.05). As compared with controls[ (2.17±0.11)× 103 U/L , (0.79±0.11)×103 U/g Pr] ,the rats exposed to higher fluoride and lower fluoride exhibited lower levels of T-AOC [(1.37±0.27)×103 U/L,(0.24±0.06)×103 U/g Prand (1.20±0.14) x 103 U/L,(0.41 ~ 0.10)×103 U/g Pr], the difference being statistically signifieant(P<0.05). As compared with controls[ (2.34±0.16) mmoL/L, (2.97±0.11)mmol/g Pr] and low fluoride exposed group[ (2.68±0.33)mmoL/L, (3.38±0.21)mmol/g Pr], higher level of MDA were observed in higher fluoride exposed group[ (3.72±0.59)retool/L, (4.01±0.21)mmol/g Pr], the difference being statistically significant(P<0.05). Conclusion The results indicated that higher amount of fluoride induced an increased level of oxidation, which might result in the decreased capacity of intelligence of rats with fluorosis.

Background Heat shock proteins (HSPs) are highly conserved proteins that are induced in cells when confronted with a wide variety of proteotoxic stresses.HSP27 has a high degree of similarity with α-crystallin protein.The abnormality of HSP27 structure and expression are closely related to the formation of cataracts.Our previous study showed sodium salieylate has the protective effect on H2O2-induced lens damage.Objective This study was to investigate the roles of MAPK signal pathway in sodium salicylate-induced the expression of HSP27 in human lens epithelial cells (LECs) in vitro.Methods Human LECs were incubated in the fresh media containing sodium salicylate at different concentrations (0-55 mmol/L) for different times (1-5 hours) and allowed to be recovered in fresh medium without sodium salicylate for 1-24 hours with or without pretreatment with P38MAPK inhibitor (SB203580), ERK1/2 inhibitor (PD98059) and JNK/SAPK inhibitor ( SP600125). The expressions of P38MAPK, EBK1/2, JNK/SAPK, phosphorylated P38MAPK, phosphorylated ERK1/2, phosphorylated JNK/SAPK and HSP27 were detected by Western blot. HSP27 mRNA was detected by RT-PCR. The expression of HSP27 was also detected by immunohistochemistry. Results There was only weak expression of HSP27 in normal human LECs.After stimulation of 35-55 mmol/L sodium salicylate was removed and human LECs were cultured again for 6 hours,the expression of HSP27 in LECs were significantly increased ( F= 509. 953,P<0. 01). HSP27 was absent expressed in human LECs in 55 mmol/L sodium salicylate stimulation for 1-5 hours groups, but LECs were re-cultured for 3,6 hours after removed the stimulation, the expression of HSP27 was elevated (F = 452. 534, P<0. 01). Activation of P38 M APK occurred after sodium salicylate stimulation 30 minutes and 1 hour ( F = 865.68, P<0. 01). However, ERK 1/2 was expressed after sodium salicylate was eliminated for 1-6 hours ( F = 388.84, P<0. 01). JNK/SAPK was inactived by sodium salicylate. The expression of HSP27 could be down-regulated with the pretreatment of SB203580 and PD98059. Conclusion Sodium salicylatc can induce the expression of HSP27 in human (LECs) . The effects are mediated,at least in part ,through the activation of P38MAPK and ERK1/2 signaling pathway .