Objective To observe the effect of depside salt from Salvia Miltiorrhiza on platelet endothelial nitric oxide synthase(eNOS) activity in health adults.Methods Peripheral venous blood was collected,platelets were isolated with gel-filtration chromatography and incubated with eNOS agonist histamine,eNOS inhibitor L-NAME and different concentrations of depside salt from Salvia Miltiorrhiza(0.1,1,10,100,1000 mg/L) for 30 minutes,then eNOS activity was measured as formation of 3H-L-citrulline from 3H-L-arginine.Results(1)Platelet eNOS activity was significantly inhibited after incubated platelets with L-NAME and increased after incubated with histamine(P

Objective To investigate the relationship between abnormal bone mineral density (BMD) and subclinical thyroid dysfunction. Methods Thyroid function, biochemical indicators of bone metabolism and BMD were reviewed retrospectively in the subjects who received health checkups from July 1, 2009 to January 31, 2017 in the Health Check-up Department of Peking Union Medical College Hospital. People who had thyroid dysfunction, recognized risk factors for osteoporosis, and medication history were excluded. A cross-sectional analysis of thyroid status and biochemical indicators of bone metabolism was performed by the standard methods. BMD at the lumbar spine and femoral neck was measured using dual energy X-ray absorptiometry. Results A total of 6884 subjects (3726 women and 3158 men) were enrolled in the study, with an average age of (50.74 ± 10.41) years. They were divided into three groups:subclinical hyperthyroid, subclinical hypothyroid, and euthyroidism. The alkaline phosphatase in subclinical hyperthyroid group was higher than that in the euthyroidism group[ (67.95±20.64)U/L vs. (63.88±18.99)U/L]. Calcium and phosphorus in blood were higher in both subclinical hyperthyroid and subclinical hypothyroid groups. The rate of abnormal BMD in male euthyroidism, subclinical hyperthyroid and subclinical hypothyroid groups were 36.10％(1049/2906), 29.27％(12/41) and 27.01％(57/211), respectively. The rate of abnormal BMD showed no difference between subclinical hyperthyroid group and euthyroidism group (P>0.05). The rate of abnormal BMD was lower in subclinical hypothyroid group than in euthyroidism group (χ2=7.0901, P<0.01), especially in the males aged 40-49 years (χ2=10.4618, P<0.01). The rate of abnormal BMD in female euthyroidism, subclinical hyperthyroid and subclinical hypothyroid groups was 38.81％(1286/3314), 45.83％ (33/72) and 40.88％ (139/340), respectively. The rate of abnormal BMD showed no difference among the three groups (P>0.05). Conclusion There is no significant difference in the rate of abnormal BMD between subclinical thyroid dysfunction group and euthyroidism group, possibly because abnormal serum biochemical indicators preceded the presence of low BMD. More sensitive methods used to determine the status of bone metabolism await to be developed.

Objective The calcium oxalate stone is the most common type of the kidney stones.By building the rat renal calcium oxalate stone model, preliminary study the function of CaSR-Claudin14 regulating pathways on renal calcium oxalate stone for-mation model in rats. Methods 30 Male S-D rats were randomly divided into control group (n=15) and model group (n=15). Adult male S-D rats were given ethylene glycol and ammonium chloride to induce urolithiasis.Application of full automatic biochemical analyzer to test rat renal function and the changes of urine biochemical index.Immunohistochemistry was used to detect the expression of CaSR protein;RT-PCR was used to detect the Claudin-14 mRNA expression;Western Blotting was used to detect the expression of CaSR and Claudin-14 protein respectively. Results By observing model group has large stones crystallization under light microsco-py;model group rats 24 h urine calcium are significantly higher than control group([9.66 ±1.10]mmol vs [3.26 ±0.60]mmol, P<0.01); and model group 24 h urine volume are significantly higher than control group ([21.27 ±1.08]mL vs [13.2 ±0.55]mL, P<0.01 ); and urinary PH has no significant difference between the groups( P >0.05 ) .Expression of Claudin-14 mRNA in the model group is significantly higher than normal control group([0.150 ± 0.004] vs [0.047 ±0.008], P<0.01); Expression of Claudin-14 protein in the model group is significantly higher than normal control group([1.526 ±0.089] vs 0, P<0.01).Expression of CaSR protein in the model group is significantly higher than normal control group([6.697 ±0.051] vs [5.016 ±0.053], P<0.05). Conclusion CaSR can raise the expression of Claudin-14, increase re-nal tubular urinary calcium excretion to promote renal calcium oxalate stone formation.

Objective: To observe the effects of electroacupuncture (EA) on uterine prostaglandin F2α (PGF2α), cyclooxygenase 2 (COX-2) and nuclear factor κB (NF-κB) in rats with primary dysmenorrhea (PD) and to discuss the possible mechanism in EA intervening PD. Methods: Forty Sprague-Dawley female rats were randomly divided into a blank group, a model group, an EA group and an ibuprofen group, with 10 rats in each group. The PD model was established using estradiol benzoate combined with oxytocin in the model group, EA group and ibuprofen group. At the same time of modeling, rats in the EA group were given EA at Guanyuan (CV 4) and Sanyinjiao (SP 6) once a day for 20 min each time for 10 consecutive days. Ibuprofen was intragastrically administered once a day for 10 consecutive days in the ibuprofen group. The same amount of normal saline was intragastrically administered once a day for 10 consecutive days in the blank group and model group. The number of writhing of rats in each group within 30 min was compared on the 11th day just after the interventions. The uterine homogenate supernatant was separated and the PGF2α level was detected by enzyme-linked immunosorbent assay. Western blot was applied for the detection of the expression levels of COX-2, phospho-NF-κB p65 and NF-κB p65 proteins in uterine tissues. Results: Compared with the blank group, the number of writhing in the model group increased significantly (P<0.01), and the expression levels of PGF2α, COX-2, phospho-NF-κB p65 and NF-κB p65 proteins in uterine tissues were significantly increased (all P<0.01). Compared with the model group, the number of writhing in the EA group and ibuprofen group were significantly reduced (both P<0.01), and the expression levels of PGF2α and COX-2 protein in uterine tissues were significantly reduced (both P<0.01). Compared with the model group, the phospho-NF-κB p65 level in uterine tissues in the EA group was significantly reduced (P<0.01). Compared with the ibuprofen group, the phospho-NF-κB p65 level in the EA group was significantly reduced (P<0.01). Conclusion: The mechanism of EA for PD rats may be related to inhibiting the phosphorylation of NF-κB and reducing the levels of COX-2 and PGF2α in uterine tissues.

Purpose To investigate the clinicopathological characteristics and the survival outcomes of invasive lobular carcinoma. Methods A retrospective analysis of 98 patients with invasive lobular carcinoma and 530 invasive carcinoma of no special type was performed in order to observe the histological features and the clinical outcomes of invasive lobular carcinoma. Results Median follow-up was 68. 5 months for invasive lobular carcinoma and 67 months for invasive carcinoma of no special type. Invasive lobular carcinoma presented with a larger tumor size, more histopathological grade 2 tumors, increased rate of hormonal receptor positivity, human epider-mal growth factor 2 (HER-2) negativity, and had a lower proliferative index as compared to invasive carcinoma of no special type, more frequently presented with the luminal A subtype (P<0. 001). The classical invasive lobular carcinoma presented with a smaller tumor size, to have a lower histological grade and proliferative index compared to the non-classic type, and more frequently presented with the luminal A subtype, whereas the non-classic invasive lobular carcinoma patients more frequently presented with the luminal B, HER-2 overexpression, or triple negative subtype (P=0. 035). A statistically significant difference in the outcome was observed at un-ivariate analysis for patients with non-classic for disease-free survival (P=0. 043) and for overall survival (P=0. 048), as compared with patients with classical invasive lobular carcinoma. The disease-free survival difference between the invasive lobular carcinoma and the invasive carcinoma of no special type was not significant (P=0. 537), and the overall survival rates were not statistically different between the two groups (P=0. 397). A statistically significant difference of overall survival was observed at multivariate analysis for patients with HER-2 positive and triple negative subtypes versus patients with luminal A invasive lobular carcinoma (P=0. 015, P=0. 016) . Conclusions The outcome of invasive lobular carcinoma is significantly correlated with histological and immunohistochemi-cally defined molecular subtypes. New tailored strategies should be explored in these subgroups of patients with poor outcome.

Purpose To investigate the expression of EZH2 and p53 protein in breast cancer and to analyze their relationship with the clinical pathologic characteristics and prognosis. Methods The expression of EZH2 and p53 protein were detected by immunohisto-chemical method in 50 cases of breast adenosis tissues, 92 cases of breast invasive lobular carcinoma ( ILC) and 200 cases of breast in-vasive ductal carcinoma ( IDC) , and their correlation was also analyzed. Results There was no statistical significance of EZH2 be-tween ILC and IDC (P>0. 016 7), while its expression in breast adenosis tissues was lower than that in ILC and IDC (P<0. 016 7). In breast cancer the expression of EZH2 protein were not correlated with patient age, menopausal status, histological types, and pTNM stage. In contrast, its expression correlated with the tumor size, lymph node metastasis, molecular subtype, survival status and p53 (P<0. 05). There was no statistical significance of p53 between ILC and breast adenosis tissues (P>0. 016 7), while its expression in IDC was higher than that in ILC and breast adenosis tissues (P<0. 016 7). Its expression had no related to patient age, menopausal status, tumor size, lymph node metastasis in breast cancer, but related to histological types, pTNM stage, molecular subtype and sur-vival status (P<0. 05). The Kaplan-Meier survival analysis showed the expression of EZH2 and p53 had correlated with disease-free and overall survival rates of breast cancer (P<0. 05). Multivariate COX regression analysis showed that the expression of EZH2 and p53 were independent affecting factors to breast cancer patients. Conclusion The expression of EZH2 and p53 protein increase in the breast adenosis, ILC and IDC gradually, and they have positive correlation. The expression levels of EZH2 and p53 protein have im-portant value to evaluate the prognosis of breast cancer patients.

Objective To explore the status of iodine nutrition in 8～10 years children after universal salt iodization(USI)in the iodine deficiency area.Methods Probability proportion to size method(PPS)or simple random sampling methods were used to sample children aged 8～10 years in iodine deficiency area in the vear 1995,1997,1999,2002 and 2005, respectively.Goiter were detected by palpation and B-ultrasound, iodine concentration in salt was detected by direct titration method and that in urine by the method of As3+-Ce4+catalytic spectrophotometry.Results After USI has been implemented,the median of salt and urinary iodine tended to mcreaseand the goiter rate tended to decrease year by year.In 2005,the coverage rate of iodinated salt was elevated to 97.2%,qualified iodize salt rate was 97.1%and edible qualified iodinated salt rate was 94.3%in the whole iodine deficiency areas.The median of urinary iodine Was 227.7 μg/L 89.7%(323/360)of the population had a level of the urinary iodine over 100μg/L Goiter rate of 8～10 years children Wag decreased from 22.3%(282/1267)to 4.4%(53/1200) from 1995 to 2005.Conclusion After 10-year USI,the status of iodine nutrition in ShaJldong Province has been promoted obviously and it is in a suitable iodine nutritional status.

Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.
Acetaminophen ; administration & dosage ; chemistry ; Administration, Oral ; Drug Delivery Systems ; Electrical Equipment and Supplies ; Electrochemical Techniques ; instrumentation ; methods ; Hydrogen Bonding ; Kinetics ; Lipids ; chemistry ; Microspheres ; Solubility ; Taste ; drug effects ; beta-Cyclodextrins ; chemistry

ObjectiveTo look into the distribution of “iodine suitable” region in iodine-deficient areas in Shandong province and to provide a scientific basis for guiding the redesignate of iodine-deficient areas and launch scientific supply of iodine.Methods One to 3 copies of water source samples were collected in 105 existing iodine-deficient counties by village.Water iodine content was detected by arsenic-cerium catalytic spectrophotometry.The areas with water iodine content below 10 μg/L was defined as iodine-deficient areas and among 10 - 150 μg/L were “iodine suitable areas” and greater than 150 μg/L were high iodine areas.Results The research was carried out in 14 cities,105 counties,and 1337 towns.We collected 65 716 water samples.Sample recovery efficiency reached 99.8％.The median of water iodine was 5.57 μg/L.In the 1337 towns surveyed,there were 82.05％(1097/1337) of the township with water iodine median ＜ 10 μg/L,17.43％(233/1337) between 10 - 150 μg/L,and 0.52％(7/1337) ＞ 150 μg/L.Conclusions In Shandong province,the water “iodine suitable” regions are distributed scattered with considerable proportion.In iodine-deficient areas,there are areas with high water iodine,and iodine-deficient regions should be redrawn.Emphasis should be put on iodine nutritional status of residents in “high iodine and iodine suitable” regions,and iodine supplementation should be carries out scientifically.

Objective To survey the highly risk iodine deficiency regions of Shandong Province and to provide reference basis for further executing urgent iodine supply. Methods The annual document of cretinism in Licheng District in Jinan City and Shouguang City, the two iodine deficiency regions, were referred. Forty children aged 8-10 years of 2 targeted schools from 3 towns out of every targeted region underwent palpation, ultrasonography and As3+-Ce4+catalyzing speetrophotometry for ultra iodine examination. Twenty women aged 18-40 years from 2 villages sampled from every targeted town received ultra iodine examination and edible salt examination of iodine with direct titration. Results No new cretinism and suspected cretinism was found since 1995 in the regions. The goiter rates of children of the two regions detected with palpation and ultrasonography were 7.5% (18/241),6.2% (15/241) and 5.0% (13/259), 1.2% (3/259), respectively. Two hundred forty and 249 urine samples were respectively collected in school children, in which the median urinary iodine was 226.3,282.7 μg/L. One hundred twenty urine samples were respectively collected from the two group of women, resulting a median urinary iodine of 187.2,321.7 μg/L. Eight and 2 salt samples were free of iodine in 120 salt samples collected each region, respectively. The rate of qualified iodized salt was 100%. Conclusions It is not necessary to urgently implement iodine supply in Shouguang City and Licheng District. However, reinforcement of supervise on salt industry and eliminating the hazard from non-iodized and disqualified iodized salt remains in need.