Adult ; Burnout, Professional ; Female ; Humans ; Life Change Events ; Middle Aged ; Occupations ; Professional Competence ; Work ; psychology ; Young Adult

To explore an efficient strategy for the conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones, an azole heterocyclic ring of oxadiazole instead of the C-3 carboxylic acid group with a functionalized hydrazone group as a modified side-chain, fifteen novel 2-(fluoroquinolon-3-yl)-oxadiazole-5- sulfanylacetylhydrazone derivatives 7a-7o were designed and synthesized on the basis of the pharmacophore hybridization principle from pefloxacin, separately. The structures for fifteen title compounds were characterized by elemental analysis, 1H NMR and MS, and their in vitro antitumor activity against Hep-3B cell line was evaluated by a MTT assay. The results showed that the title compounds exhibited more significantly inhibitory activity than that of the parent pefloxacin, in which compounds with electron-withdrawing group attached on aryl ring had more potency than that of compounds with electron donating group, especially compounds with a carboxylic substituent were comparable to comparison doxorubicin. It suggests that it is favorable for an improvement of antitumor activity to remain a carboxylic acid unit at the aromatic ring.
Antineoplastic Agents ; chemical synthesis ; chemistry ; Cell Line, Tumor ; Fluoroquinolones ; chemistry ; Humans ; Oxadiazoles ; chemistry ; Structure-Activity Relationship

To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.
Animals ; Anti-Bacterial Agents ; chemical synthesis ; chemistry ; Antineoplastic Agents ; chemical synthesis ; chemistry ; Carboxylic Acids ; Carcinoma, Hepatocellular ; Cell Line ; Cell Proliferation ; Drug Design ; Escherichia coli ; drug effects ; Fluoroquinolones ; chemical synthesis ; chemistry ; HL-60 Cells ; Humans ; Leukemia L1210 ; Liver Neoplasms ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Mice ; Naphthyridines ; Triazines

Objective To examine the expressions of glyoxalase Ⅰ (GLO-Ⅰ ) in endometrial cancer tissues and cell lines and to investigate the roles of GLO-Ⅰ on proliferation and apoptosis in endometrial cancer cells. Methods Immunohistochemistry, western blot and RT-PCR were used to investigate the expressions of GLO-Ⅰ protein and mRNA in endometrial cancer tissues and Ishikawa cell lines ;enzyme activity of GLO-Ⅰ in normal endometrium, endometrial cancer and paraneoplastic tissue samples was detected with spectrophotometer; proliferation and apoptosis of Ishikawa cell before and after RNA interference (RNAi) procedure were detected by the methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. Results (1)There were significant differences of GLO-Ⅰ expression between normal endometrium (0/19) and endometrial cancer tissues ( 76%, 22/29 ); these were also significant differences of enzyme activity of GLO-Ⅰ among normal endometrium, paraneoplastic and endometrial cancer tissues( 1.1,0.8 vs 92.3 IU/mg; P <0.01 ). Enzyme activity of GLO-Ⅰ in fresh normal endometrium and paraneoplastic tissues was weak, while that of fresh endometrial cancer tissues was as high as 92. 3 IU/mg in average. (2)The expression of GLO-Ⅰ mRNA in Ishikawa cell transfected with GLO-Ⅰ siRNA was significantly lower than that in negative group (0.25 ± 0.06 vs 0.93 ± 0.10, P < 0.0l ), and the similar results that in the expression of GLO-Ⅰ protein (0.38 ±0.06 vs 0.94 ±0.13, P <0.01 ). (3) Proliferation in Ishikawa cell was significantly inhibited after silencing RNA expression of GLO-Ⅰ ( P = 0.028 ). The apoptosis rate of cells transfected with GLO- Ⅰ siRNA was significantly higher than that of negative control group and blank control group [ ( 6.7 ± 0.8 ) % vs ( 1.2 ± 0.4) %, ( 1.4 ± 0.4 ) %; P < 0.01 ]. Conclusion The expression and enzyme activity of GLO- Ⅰ is significantly increased in endometrial cancer, which could promote abnormal proliferation and inhibit apoptosis in endometrial cancer cells.

Objective To investigate the efficacy of spectral entropy measurement in reflection of depth of anesthesia and noxious stimulation. Methods Forty-five patients of ASAⅠorⅡ were randomly divided into three groups(n=15).Group A,B and C received fentanyl 1,3 and 5 ?g/kg,respectively,3 min before target controlled infusion(TCI) of propofol.Intubation was performed when the effect-site concentration(CE)reached 3.5 ?g/mL,which was maintained until 5 min after incision.Response entropy(RE),State entropy(SE) as well as heart rate(HR),mean arterial pressure(MAP) were measured at the time points of before fentanyl and 2,3 min after fentanyl,every CE of propofol steps,before intubation,immediately and 1,3,5 min after intubation,before skin incision,and 0.5,1,3,5 min after skin incision,respectively. Results Three minutes after receiving fentanyl,the values of RE and SE in the three groups decreased significantly in a dose-dependent manner,and increased obviously at the same degree during intubation and after skin incision.The values recovered to the level before stress stimulation 1 min after intubation and 5 min after skin incision.There were no differences in the fluctuation of RE and SE among the three groups when the CE of propofol reached 1.0 ?g/mL.Conclusion Spectral entropy may effectively reflect the depth of anesthesia,but not analgesia during anesthesia.

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.

AlM: To introduce a new color pediatric visual acuity chart and its clinical application.
METHODS:The color pediatric visual acuity chart was designed based on principle of visual angle. The optotype on the color chart had graphics. The progression rate of optotype size between 2 lines was 10 10 and 1. 2589. A regular geometric progression of optotype sizes and distribution was employed to arrange 8 lines with 11 optotype on the color chart. The testing distance was 3m. The visual acuity score could be recorded as logarithm of the minimum angle of resolution notation or decimal notation. The reliability of naked distant measurements with this new chart was tested in one eye of 100 children (4 ~ 6 years old) taking the Chinese national standard logarithm visual acuity chart standard.
RESULTS: The color pediatric visual acuity chart and logarithmic chart controls, visual acuity test results that in the two groups had no significant difference (t=1. 2671, P> 0. 05 ). Two sets of vision data existed positive correlation (r= 0. 924, P<0. 01). Cooperation rate was 100%, the recognition rate was more than 90%.
CONCLUSlON:Children are easier to accept used new color pediatric visual acuity chart to inspect vision. New chart is reliability and apply to children's vision screening.

BACKGROUND:Fibrin glue introduced into calcium phosphate cement has not been confirmed whether this way could overcome the compressive limits and the low degradation of calcium phosphate cement and to modify the biological properties of calcium phosphate cement. OBJECTIVE:To explore the mechanical and biological properties of calcium phosphate cement/fibrin glue at different powder/liquid ratio for bone regeneration in vitro. METHODS:Calcium phosphate cement and fibrin glue were mixed at ratios of 1:1, 3:1, 5:1 (mL/g), and the pure calcium phosphate cement served as controls. Setting time, scanning electron microscope and the biomechanical test were used to analyze the composite scaffold structure, physical performance and the mechanical properties. Passage 3 osteoblasts were respectively inoculated on the material surface of the four groups, and pure cells served as blank controls. celladhesion, proliferation and alkaline phosphatase activity were observed. RESULTS AND CONCLUSION:The initial and final setting time of calcium phosphate cement/fibrin glue at 1:1 and 3:1 (mL/g) was higher than that in the control group (P<0.05), while the initial and final setting time of calcium phosphate cement/fibrin glue at 5:1 (mL/g) was lower than that of the control group (P<0.05). Scanning electron microscope showed smoother and denser surface of composite scaffolds compared with the pure calcium phosphate cement. The aperture of the composite scaffolds was decreased with the increasing concentration of fibrin glue. The compressive strength of composite scaffolds at 3:1 and 5:1 was higher than that of the control group (P<0.05), while the modulus of the composite scaffolds at 1:1, 3:1, 5:1 was higher than that of the control group (P<0.05). celladhesion, proliferation and alkaline phosphatase activity showed no difference among the three composite scaffold and control groups, but al higher than the blank control group (P<0.05). These findings indicate that fibrin glue introduced into calcium phosphate cement can overcome the low-strength limits of calcium phosphate cement, and maintain the good biological properties of calcium phosphate cement for bone regeneration.

Objective To investigate the hypoglycemic effects of Laminaria japonica (L. japonica) on diabetic model induced by alloxan in rats. Methods Sixty healthy female rats were used to establish diabetic models by injecting alloxan peritoneally, and L.japonica was applied as raw materials for potential marine drugs.The levels of fasting blood glucose (FBG) were detected by automatic blood glucose device. Enzyme linkedimmunoabsorbant assay was applied to determine the insulin level in serum. The shape and structure of isletcells were observed with histopathological staining, and the expression of superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) in islet cells were detected by immunohistochemical technique. Results After the treatment, the levels of FBG of L.japonica treated group B [(9.37±1.70) mmol/LandC (9.18±1.65 ) mmol/L, F= 32.81, q=6.35～11.72, P<0.05 ] reduced, while the serum levels of insulin in treated group A, Band C (0.0378±0.0026, 0.0378±0.0027, 0.0367±0.0035) increased(F= 11.40, q=4.28～8.47, P<0.05) significantly than those of diabetic model group (0.0456 ±0.0057) . The shape and structure of islet cells improved with the up-expressing SOD(t=4.73～4.76, P<0.05)and down-expressing iNOS (t=4.81～5.30, P<0.05) in L.japonica treated group B and C than those in diabetic model group. Conclusion L.japonica might decrease the serum level of FBG through promoting the islet cell recovery by an anti-oxide effect.

Objective:To determine drug dose and usage of timolol maleate eye drops in the treatment of superficial infantile hemangioma.Methods:A total of 250 superficial hemangioma infants were recruited and assigned into 5 groups (n=50 for each group):an external application group and 4 exterior coating groups (2,4,6,8 times per day).We evaluated the therapeutic effect of different methods for drug application (external application or exterior coating) and the frequency for drug administration on superficial infantile hemangioma.Results:The external application group (twice a day and 0.5 hour per time) showed better effect than that in the exterior coating group with twice a day (P＜0.001).The difference in therapeutic effect between the exterior coating group with 6 times a day and exterior coating group with twice a day or with 3 times a day was significant (P＜0.001).The differences in drug efficacy were not found among the exterior coating group with 6 times a day,the exterior coating group with 8 times a day,or the external application group with twice a day (All P＞0.05).Conclusion:Drug dose may affect the therapeutic effect oftimolol maleate eye drops in superficial hemangioma infants,and exterior coating with 6 times a day may achieve the best curative effect.