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.

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.

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.

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

BackgroundIt has been proved that as a chemokine,interferon-inducible protein-10(IP-10)can regulate the immuno-inflammatory reaction.Some new researches showed that IP-10 also played role in regulating the neovascular vessel formation.Corneal neovascularization (CNV) is associated with multiple cellular factors,but its mechanism is below clear.Objective The present study was to address the roles of exogenous mouse IP-10 in alkali burn-induced CNV.Methods Eighty-two SPF BALB/c mice were used in this experiment and grouped according to random number table.The corneal alkali burn models were established by putting the filter paper with 1 mol/L NaOH at the central corneas of the left eyes for 40 seconds.10 mg/L IP-10 was topically administered from the first day or 14 days after modeling in the early intervene group( 10 eyes)or middle-late intervene group(5 eyes).CNV area was measured as a percentage of whole cornea.0.2％ sodium hyaluronate(HA) as vehicle was utilized in the model control group.Angiogenic factor expression in corneal tissue in the early intervene group was quantified by reverse transcriptase polymerase chain reaction (RT-PCR)and compared with model control group.All animal experiments were performed in accordance with the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research and complied with the standards of Guidelines for the Care and Use of Laboratory Animals of Soochow University. ResultsThe CNV percentage was(88.67±10.22) ％ in the model control mice,showing a significant increase in comparison with that of IP-10 early intervene group (70.06±12.21)％ (t=3.77,P=0.00).In 21 days after corneal alkali burn,the CNV percentage was(87.33±13.47)％ in the model control mice,and that of the IP-10 middle-late intervene group was ( 86.56± 12.47 ) ％ without significant difference between them ( t =1.26,P＞0.05 ).Two days or four days after IP-10 early intervene,the expressions of chemokine receptor type 3 ( CXCR3 ) in corneal tissue were significant higher than model control group( t =3.13,3.07,P＜0.05 ),but the expressions of vascular endothelial growth factor (VEGF) in cornea were lowed ( t =5.99,6.27,P＜0.01),and so were transforming growth factor-β1 (TGF-β1) (t =8.50,P＜0.01;t =4.53,P＜0.05).Conclusions The early topical administration of the exogenous mouse IP-10 can inhibit CNV by up-regulating CXCR3 expression and down-regulating VEGF and TGF-β1 expression in cornea.However,middle-later usage of the IP-10 is uneffective.

Objective To evaluate the efficacy and safety of fully covered self-expandable metal stents (FCSEMS) implanted by endoscopic retrograde cholangiopancreatography (ERCP) for patients with benign biliary stricture (BBS).Methods The clinical data of 38 patients with BBS underwent ERCP and FCSEMS placement between January 2012 and January 2016 were retrospectively recorded.Success rate of BBS,adverse events related to ERCP and stricture recurrence were analyzed.Results A total of 38 patients underwent FCSEMS placement with a mean time of stent in dwelling for 8 months (range:3-13months).During follow-up after the stent was removed,death of 1 patient after liver transplantation was due to unrelated cause.The mean follow-up time was 13 months (range:2-52 months) for other patients.Stricture recurrence occurred in 6 patients,including 2 cases of gallstone-related biliary strictures,1 case of chronic pancreatitis-related biliary strictures,2 cases of liver transplantation-related biliary strictures,and 1 case of post surgical-related biliary strictures.Stricture resolution occurred in 31 cases with 83.8％ (31/37) success rate,including 90.0％ (18/20) gallstone-related biliary strictures,75.0％ (3/4) chronic pancreatitis-related biliary strictures,80.0％ (8/10) liver transplantation-related biliary strictures,and 66.7％ (2/3)post surgical-related biliary strictures.The incidence of post-ERCP complications was 21.1％ (8/38),including mild pancreatitis in 5 case,hyperamylasemia in 2 cases,cholangitis in 1 case.All patients were cured by conservative treatment.Conclusion FCSEMS are effective and safe for BBS.Further studies are needed to assess the indwelling time of FCSEMS,whether FCSEMS are superior to multiple plastic stents and the different efficacy of FCSEMS for BBS caused by different etiology.

Malignant tumors are major diseases that endanger human health. Due to their complex and variable microenvironment, most anti-tumor drugs cannot precisely reach the focal tissue and be released in a controlled manner. Intelligent responsive nano carriers have become a hot spot in the field of anti-tumor drug delivery systems. As an excellent nano material, mesoporous silica has the advantages of non-toxic, stable, adjustable pore volume and pore diameter, and easy functional modification on the surface. By virtue of its perceptive response to the tumor microenvironment or physiological changes, it can achieve the targeted drug release or controlled drug release of the drug delivery system in the tissue, making it an ideal carrier for intelligent response drug delivery system. In this paper, we review the design strategies and current research status of smart responsive anti-tumor drug delivery systems based on mesoporous silica, in order to provide a reference for the development of anti-tumor drug nanoformulations.

A series of cycloberberine derivatives were designed, synthesized and evaluated for their anti-cancer activities in vitro. Among these analogs, compounds 6c, 6e and 6g showed strong inhibition on human HepG2 cells. They afforded a potent effect against DOX-resistant MCF-7 breast cells as well. The primary mechanism showed that cell cycle was blocked at G2/M phase of HepG2 cells treated with 6g using flow cytometry assay. It significantly inhibited the activity of DNA Top I at the concentration of 0.1 mg mL-1. Our results provided a basis for the development of this kind of compounds as novel anti-cancer agents.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Berberine ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; DNA Topoisomerases, Type I ; metabolism ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Molecular Structure ; Structure-Activity Relationship

Objective To evaluate the damage caused by high intensity ultrasound(HIU)on tumor micro- vessels.Methods Rabbit models of the VX_2 tumor were set up.The target hepatic carcinomas were treated with HIU,and the results were observed using hematoxylin-eosin(HE)staining,vascular endothelial cell biotinylated-ulex europaeus agglutininiⅠ(UEAI)immunohistochemical staining,tumor micro-vessel counts,and electron microscopy. Results Histological examination through HE staining indicated that HIU induced carcinoma vascularities with whole tumor tissue coagulative necrosis.The UEAI immunohistochemical staining of the target lesions treated by HIU was ne- gative,and complete tumor micro-vessel uhrastructure damage was observed under the electron microscope.Conclu- sion HIU can damage tumor micro-vessels thoroughly,in such way that it may inhibit tumor growth and metastasis.

Head and Neck Neoplasms ; surgery ; Hemangioma, Cavernous ; surgery ; Humans ; Infant ; Thoracic Neoplasms ; surgery