[Survey on characteristics of menopause of Chinese women with the age of 40-60 years at gynecological clinic from 14 hospitals].

OBJECTIVE: To investigate the characteristics of menopause of Chinese women with the age of 40-60 years concerning gynecologic clinics in China. METHODS: From Mar.2008 to Sept.2008, a face-to-face questionnaire was conducted in gynecological clinic in perimenopausal and postmenopausal women in 14 hospitals in China, which included general demographic data, menstrual change process, climacteric symptoms and knowledge about menopause. Modified Kupperman index were used to evaluate climacteric symptoms during the recent week and awareness of hormonal replacement therapy were studied. RESULTS: A total of 1641 women were investigated. The ages of onset of menopause transition, climacteric symptoms and natural menopause were (47 ± 4), (46 ± 4), (49 ± 3) years old respectively. Climacteric symptoms could be found in 78.43% (1287/1641) women during menopausal transition, which were mainly mild to moderate symptoms. The top 5 symptoms were fatigue and weakness (71.48%, 1173/1641), irritability (68.68%, 1127/1641), insomnia (67.65%, 1110/1641), muscle and joint pain (64.11%, 1052/1641) and hot flush (57.90%, 950/1641). The climacteric symptoms were not constant during menopausal transition, usually more severe in late transition and postmenopausal periods, during which the moderate and severe symptoms were 59.1% (189/320) and 51.1% (291/570) respectively. Although most symptoms primarily appeared along with menstruation change, there are about 17.5% (172/981) patients experienced climacteric symptoms before menstruation change occurrence. There were 56.39% (733/1300) women had ever heard (mostly from gynecologist) about hormone replacement therapy from Obstetrician and Gynecologist. CONCLUSIONS: Most of the women during menopausal transition had climacteric symptoms, usually mild and moderate ones. Although most symptoms primarily appeared along with menstruation change, there are other patients' experienced climacteric symptoms before menstruation change occurrence.

Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying a bispecific T cell engager against hepatocellular carcinoma.

We previously established a hepatocellular carcinoma (HCC) targeting system of conditionally replicative adenovirus (CRAd) delivered by human umbilical cord-derived mesenchymal stem cells (HUMSCs). However, this system needed to be developed further to enhance the antitumor effect and overcome the limitations caused by the alpha-fetoprotein (AFP) heterogeneity of HCC. In this study, a bispecific T cell engager (BiTE) targeting programmed death ligand 1 controlled by the human telomerase reverse transcriptase promoter was armed on the CRAd of the old system. It was demonstrated on orthotopic transplantation model mice that the new system had a better anti-tumor effect with no more damage to extrahepatic organs and less liver injury, and the infiltration and activation of T cells were significantly enhanced in the tumor tissues of the model mice treated with the new system. Importantly, we confirmed that the new system eliminated the AFP-negative cells on AFP heterogeneous tumor models efficiently. Conclusion: Compared with the old system, the new system provided a more effective and safer strategy against HCC.

A Novel CD3/BCMA Bispecific T-cell Redirecting Antibody for the Treatment of Multiple Myeloma.

Multiple myeloma (MM) is a B-cell malignancy for which new treatments are urgently needed. Redirecting the activity of T cells by bispecific antibodies against tumor cells is a potent approach. The B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein and therefore is an ideal therapeutic target for T-cell redirecting therapies. The main objective of this work is to target the BCMA by generating BCMA-specific murine monoclonal antibody and construct a cluster of differentiation 3 (CD3)/BCMA-directed tandem diabodies (Tandab). In brief, using standard hybridoma technology, we developed a novel BCMA-specific monoclonal antibody (clone 69G8), that specifically bind with BCMA+ cell lines and MM patient sample; whereas BCMA- cells were not recognized. For T cells by bispecific antibodies application, we constructed a Tandab (CD3/BCMA) simultaneously targeting both CD3 and BCMA and our studies demonstrated that Tandab (CD3/BCMA) was functional with specific binding capability both for CD3+ cells and BCMA+ cells. It induced selective, dose-dependent lysis of BCMA+ cell lines, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA- cells were not affected. Furthermore, we demonstrated that Tandab activity correlates with BCMA expression, with higher potency observed in highly BCMA expressing tumor cells. In vivo, the purified Tandab (CD3/BCMA) significantly inhibited the tumor growth in a subcutaneous NCI-H929 xenograft model. Taken together, these results show that the Tandab (CD3/BCMA) displays potent and selective anti-MM activities and represents a promising immunotherapeutic for the treatment of MM.

Targeted Near-Infrared Fluorescent Turn-on Nanoprobe for Activatable Imaging and Effective Phototherapy of Cancer Cells.

A novel and green multifunctional nanoplatform as a nanocarrier for drug delivery, cell imaging, and phototherapy has been engineered. The nanoplatform is composed of stabilized carbon spheres (CSs) as cores, a coated polydopamine (PDA) shell, targeted folic acid (FA), and the loaded anticancer drug indocyanine green (ICG), obtaining CSs@PDA-FA@ICG nanocomposites (NCs). The biocompatible PDA shell provided a high fluorescence quenching efficiency and a surface rich in functional groups for anchoring FA for targeting cancer cells. Aromatic ICG could be effectively loaded into the CSs@PDA-FA system via hydrophobic interactions and π-π stacking with a loading efficiency of 58.9%. Notably, the activated NIR fluorescence in an intracellular environment made CSs@PDA-FA@ICG a sensitive "OFF" to "ON" nanoprobe that can be used for NIR imaging. Moreover, compared to ICG alone, the CSs@PDA-FA@ICG NCs could induce efficient photoconversion for simultaneous synergetic photodynamic therapy (PDT) and photothermal therapy (PTT) under a single NIR laser irradiation. The results demonstrated that CSs@PDA-FA@ICG NCs as a targeted and activated nanoplatform provide new opportunities to facilitate the accurate diagnosis of cancer and enhanced treatment efficacy. This work stimulates more interest in the design of the facile surface functionalization strategy to construct other multifunctional nanocomposites, such as nanotubes and nanorods.

Highly sensitive enzyme-free immunosorbent assay for porcine circovirus type 2 antibody using Au-Pt/SiO2 nanocomposites as labels.

Improving the performance of conventional enzyme-linked immunosorbent assay (ELISA) is of great importance to meet the demand of early clinical diagnosis of various diseases. Herein, we report a feasible enzyme-free immunosorbent assay (EFISA) system using antibody conjugated Au-Pt/SiO2 nanocomposites (APS NCs) as labels. In this system, Au-Pt/SiO2 nanospheres (APS NPs) were first synthesized by wet chemical method and exhibited intrinsic peroxidase and catalase-like activity with excellent water-solubility. Then APS NCs were utilized as labels to replace HRP conjugated antibody, and Fe3O4 magnetic beads (MBs) to entrap the analyte. To discuss the performance of EFISA system, Human IgG was served as a model analyte, and porcine circovirus type 2 (PCV2) serums as real samples. The system boosted the detection limit of HIgG to 75pgmL(-1) with a RSD below 5%, a 264-fold improvement as compared with conventional ELISA. This is the first time that APS NCs have been used and successfully optimized for the sensitive dilution detection of PCV2 antibody (5:10(7)) in ELISA. Besides, APS NCs have advantages related to low cost, easy preparation, good stability and tunable catalytic activity, which make them a potent enzyme mimetic candidate and may find potential applications in bioassays and clinical diagnostics.

[Effects of the liposomes coated by chitosan and its derivatives on the gastrointestinal transit of insulin].

AIM: To study the effect of the liposomes coated by chitosan and its derivatives as oral dosage form for peptide drugs on the gastrointestinal (GI) transit of drugs. METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. The in situ perfusion experiment was used to investigate the enteral absorption of insulin. The hypoglycemic effects of insulin were investigated using the glucose oxidase method after administration in rats. The insulin concentrations of serum and enteral tissues were determined by radio-immunoassay in rats. RESULTS: In in situ local intestinal perfusion experiment, the duodenum was the best segment for the absorption of the insulin liposomes coated by chitosan (CH) or chitosan-EDTA conjugates (CEC) , and double-coated by CH-CEC; the colon was the best segment for the absorption of the insulin solution from rat intestine; but the best segment for the absorption of the uncoated and N-trimethyl chitosan chloride (TMC) coated insulin liposomes was unclear. In all segments, the enteral absorption of the insulin liposomes double-coated by CH-CEC was superior to that of other insulin liposomes. CONCLUSION: The insulin-liposomes coated by chitosan and its derivatives can enhance enteral absorption of insulin and increase stability of insulin in GI tract.

Synthesis of functionalized 3D porous graphene using both ionic liquid and SiO2 spheres as "spacers" for high-performance application in supercapacitors.

In this work, a high-capacity supercapacitor material based on functionalized three-dimensional (3D) porous graphene was fabricated by low temperature hydrothermal treatment of graphene oxide (GO) using both ionic liquid (IL) and SiO2 spheres as "spacers". In the synthesis, the introduction of dual "spacers" effectively enlarged the interspace between graphene sheets and suppressed their re-stacking. In addition, the IL also acted as a structure-directing agent playing a crucial role in inducing the formation of unique 3D architectures. Consequently, fast electron/ion transport channels were successfully constructed and numerous oxygen-containing groups on graphene sheets were effectively reserved, which had unique advantages in decreasing ion diffusion resistance and providing additional pseudocapacitance. As expected, the obtained material exhibited superior specific capacitance and rate capability compared to single "spacer" designed electrodes and simultaneously maintained excellent cycling stability. In particular, there was nearly no loss of its initial capacitance after 3000 cycles. In addition, we further assembled a symmetric two-electrode device using the material, which showed outstanding flexibility and low equivalent series resistance (ESR). More importantly, it was capable of yielding a maximum power density of about 13.3 kW kg(-1) with an energy density of about 7.0 W h kg(-1) at a voltage of 1.0 V in 1 M H2SO4 electrolyte. All these impressive results demonstrate that the material obtained by this approach is greatly promising for application in high-performance supercapacitors.

[Studies on the insulin-liposomes double-coated by chitosan and chitosan-EDTA conjugates].

AIM: To evaluate the characteristics, the hypoglycemic efficacy and the pharmacokinetics of the insulin-liposomes double-coated by chitosan (CH) and chitosan-EDTA conjugates (CEC). METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. The protection of insulin against peptic and tryptic digestion was studied with HPLC. The hypoglycemic effects of insulin-liposomes were investigated using the glucose oxidase method after oral administration to rats. Serum insulin concentration in rats were determined by radio-immunoassay, and were assessed by Pkanalyst computer program. RESULTS: The insulin-liposomes double-coated by CH and CEC was shown to protect insulin against digestion of pepsin, trypsin and gastrointestinal contents. In glucose tolerance test in normal rats, as compared with phosphate buffer solution control group, the insulin-liposomes coated by CH and CEC could reduce the glucose-induced peak of hyperglycemia. The reduction of the insulin-liposomes double-coated by CH and CEC was superior to that of other insulin-liposomes. When administered intragastrically to normal rats, the insulin-liposomes coated by CH and CEC could reduce glycemia measured after an overnight fast. The hypoglycemic effect the insulin-liposomes double-coated by CH and CEC was superior to that of other insulin-liposomes, and the dosage of 50 mu x kg(-1) decreased by 45.98% of initial blood glucose level at 1 h. As compared with subcutaneous injection, the relative pharmacological bioavailability was 17.02% calculated by area under the curve of glucose level versus time profile after oral administration of the insulin-liposomes double-coated by CH and CEC to rats. The serum insulin concentration-time curves were found to best fit the one-compartment open model. As compared with subcutaneous injection, the relative bioavailability was 8.91% calculated by the area under the curve of serum insulin concentration versus time profile after oral administration of the insulin-liposomes double-coated by CH and CEC to rats. CONCLUSION: The stability and absorption of insulin-liposomes double-coated by CH and CEC was superior to that of the insulin-liposomes coated either by CH, or by CEC respectively.

[Trabeculectomy with amniotic membrane transplantation and combining suture lysis of scleral flap in complicated glaucoma].

OBJECTIVE: To study and evaluate the outcome of trabeculectomy with amniotic membrane transplantation combining suture lysis of scleral flap in complicated glaucoma. METHODS: This operation was performed in 48 patients (67 eyes) with complicated glaucoma. Amniotic membrane was implanted under the scleral flap and the conjunctival flap and combined with suture lysis for scleral flap to control the outflow of the aqueous humor. RESULTS: Follow-up period ranged from 5 to 38 months (mean 19.5 months). The intraocular pressure (IOP) was lowered from (43.86 +/- 7.12) mm Hg (preoperative IOP) to postoperative (19.63 +/- 2.57) mm Hg (postoperative IOP) in neovascular glaucoma (t = 4.96, P < 0.001); from (40.31 +/- 4.79) mm Hg to (18.09 +/- 2.21) mm Hg in glaucoma after IOL implant (t = 3.54, P < 0.05); from (37.94 +/- 5.63) mm Hg to (20.14 +/- 3.15) mm Hg in aphakic glaucoma (t = 5.12, P < 0.05); from (32.48 +/- 3.98) mm Hg to (16.54 +/- 1.84) mm Hg in juvenile glaucoma (t = 4.23, P < 0.01); from (36.01 +/- 4.13) mm Hg to (18.11 +/- 3.40) mm Hg in uveitic glaucoma (t = 4.47, P < 0.01); from (34.43 +/- 5.28) mm Hg to (18.31 +/- 1.52) mm Hg in glaucoma after failure of conventional filtering operation (t = 2.05, P < 0.05). Statistical significant difference was found in the IOP before and after the operation. The rate of formation of functional bulb was 80.6%. There were no reject reaction and severe complications. CONCLUSION: Trabeculectomy with amniotic membrane transplantation combining suture lysis of scleral flap is a useful method in complicated glaucoma.