Background Inflammation and adipogenesis are two parallel processes with increasing activity in severe thyroid-associated ophthalmopathy(TAO),and mevastatin was proved to have the inhibiting effect on the differentiation of adipose.Objective The aim of this work was to investigate the effects of mevastatin on the expression of cyclooxygenase-2(COX-2)and peroxisome proliferator activated receptor-γ(PPAR-γ)and differentiation of TAO-derived orbital preadipocytes,and explore its modulation effects on lipopolysaccharide(LPS)induced inflammation and the differentiation of TAO-derived orbital preadipocytes in vitro.Methods The retroorbital adipose tissue was obtained from 4 TAO patients during the surgery.The orbital fibroblasts were cultured from orbital adipose tissues using explant culture method.To study the suppressing effect of mevastatin on inflammatory response,cultured cells were divided into 5 groups.The 1000 μg/L LPS orbital fibroblasts were stimulated for 8 hours in group A,and 1000 μg/L LPS combined with 5 μmol/L,10 μmoL/L or 20 μmoL/L mevastatin were used respectively for the substitute in the group B,group C and group D.The orbital fibroblasts in group E were cultured routinely without any intervention as control.To observe the inhibiting effect of mevastatin on the differentiation of adipose,the group A were then subdivided into group A1-A6.After 1000 μg/L LPS was used to treat the cells for 8 hours,the ceils were induced to differentiate into adipocytes.All orbital preadipocytes from A1 to A6 were stimulated to differentiate into mature adipocytes with cocktail differentiation medium for a 10-day duration.During the procedure,group A2,A3 and A4 were interfered with 5,10 or 20 μmol/L mevastatin,and in the group A5 and A6,10 μmol/L mevastatin were added at the fourth day or eighth day.Intracellular fat accumulation in differentiated adipocytes was determined by oil red O staining.The absorption(A492 nm)was measured in the ceils by enzyme-linked immunosorbent assay(ELISA).Expression of COX-2 and PPAR-γ mRNA was detected by reverse transcription polymerase chain reaction(RT-PCR),and the expression of COX-2 and PPAR-γ protein was detected by Westernblot.The level of PGE2 in the supernatant was detected by ELISA.Results The expression of COX-2 protein and mRNA as well as the PGE2 levels in B,C,D group decreased markedly in comparison with those in A group(P＜0.05).With the increase of mevastatin concentration,the expression of COX-2 protein and mRNA as well as the PGE2 levels in B,C,D groups decreased successively(F =228.380,101.745,1586.881,P＜0.05).The expression of COX-2 protein and mRNA and PGE2 levels in E group were lower significantly than those in A,B and C groups(P＜0.05),but no significant differences were found between E group and D group(P＞0.05).The A492 value and the expressions of PPAR-γ protein and mRNA in differentiated cells showed the successively decrease in A1-A4 group with the elevation of mevastatin concentration(P＜0.05),and the evidently decreased A492 value and the expressions of PPAR-γ protein and mRNA also were seen in A1 and A5 groups compared with A3 group(P ＜ 0.05).Conclusions Mevastatin inhibits LPS-induced COX-2 expression,PPAR-γ expression,PGE2 secretion and differentiation of TAO-derived orbital fibroblasts in vitro in dose-dependent manner.Mevastatin plays these effect more prominently in early stage of adipocytes differentiation.

The concentration of precursors for the production of taxol with Fusarium mairei K178 was optimized by response surface methodology.Firstly,Plackett-Burman design was undertaken to evaluate the effects of eight factors.With statistic regression analysis,the significant factors affecting taxol production were determined as follows: phenylalanine,sodium acetate and sodium benzoate.Box-Behnken design was used to optimize the three critical internal factors mentioned above,and the optimum concentration levels and the relationships among these factors was found out.By quadratic regression model equation with Design-Expert statistic methods,the optimal concentration of the variables were determined as: phenylalanine 2.8mg/L,sodium acetate 3.3g/L,sodium benzoate 31.8mg/L.Under such conditions,the taxol production was increased to 242.6?g/L,which was 15.6% higher than the maximum value in the single factor tests.The experiment values under the optimal conditions agreed with the predicted values,which indicated that the model was proper and effective.

To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC). The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.
Administration, Cutaneous ; Aerosols ; Animals ; Azepines ; chemistry ; Calorimetry, Differential Scanning ; Cellulose ; analogs & derivatives ; chemistry ; Citrates ; chemistry ; Drug Delivery Systems ; Estradiol ; administration & dosage ; pharmacokinetics ; Plasticizers ; chemistry ; Polymers ; chemistry ; Skin Absorption ; Swine

A UPLC-MS/MS method based on metabonomic skills was developed to study the serum metabolic changes of rats after acute liver injury induced by CCl4 and to evaluate the action mechanism of Si-Ni-San. The integrated data were exported for principal components analysis (PCA) by using SIMCA-P software, in order to find the potential biomarkers. It showed that clear separation of healthy control group, model group, silymarin group, Si-Ni-San group was achieved by using the PCA method. Nine significantly changed metabolites were identified as potential biomarkers of acute liver injury. Compared with the health control group, the model group rats showed higher levels of phenylalanine, tryptophan and GCDCA together with lower levels of LPC 16 : 0, LPC 18 : 0, LPC 18 : 1, LPC 16 : 1, LPC 20 : 4 and LPC 22 : 6. These changes of serum metabolites suggested that the disorders of amino acid metabolism, lipid metabolism, bile acid biosynthesis and anti-oxidative damage were related to acute liver injury induced by CCl4. Si-Ni-San might have the anti-liver injury effect on all these four metabolic pathways.

Objective To evaluate the efficacy and safety of photodynamic therapy(PDT)combined with intravitreaIinjection of bevacizumab for choroidal neovascularization(CNV)caused by agerelated macular degeneration(AMD). Methods A total of 21 eyes of 21 patients with AMD,which was diagnosed by examination of visual acuity,intraocular pressure,ocular fundus,fundus color photography,fundus fluoreseein angiography(FFA),indocyanine green angiography(ICGA)and optic coherence tomography(OCT),were underwent PDT combined with intravitreal injection of Bevacizumab.The patients,15 males(15 eyes)and 6 females(6 eyes),aged from 56 to 78 years,with the average of 68.6years.The best corrected visual acuity:counting fingers/10cm-0.9,logMAR was 1.04±0.41.CNV located in below or side central fovea of macula.There was obvious leakage of fluorescein which examined by FFA and ICGA.The average of retinal thickness of macular foveal was(258.91±78.66)μm.The treatment method of PDT has to according to the way of PDT for TAP and Verteporfin PDT for VIP.Intravitreal infeetion with 1.5mg bevacizumab was performed after three days under surface anesthesia.Follow-up time was 1,3,6,12 months after the treatment. Resuits At last visit,the best corrected visual acuity:counting fingers/10 cm-1.5,logMAR was 1.04±0.41,and the differences are statistically significant compared with before.The BCVA improved four or more lines in 6 eyes(28.57%),improved two to four lines in 9 eyes(42.86%),stabilized(±1 line or no change)in 6 eyes(28.57%)and decreased in none.The average intraocular pressure was(15.20±2.41)mmHg after surgery,and the differences was not statistically significant compared with before(P＞0.05).FFA and lCGA showed CNV complete closure in 13 eyes(61.90%).partial closure in 8 eyes(38.10%).The average of retinal thickness of macular foveal was(127.38±20.14)μm(P＜0.01). Conclusion Combining treatment with PDT and intravitreal injection of Bevacizumab is safe and effective for CNV which caused by AMD.It has significant improvement in BCVA.1eakage of CNV and retinal edema.

Objective To summarize the features of esophageal hiatus hernia (EHH) on contrast-enhanced ultrasound (CEUS) and investigate the diagnostic value of CEUS in EHH.Methods A retrospective analysis of 88 EHH patients and 50 healthy controls was conducted with focus on their findings on CEUS.Results The structures of the cardiac and abdominal esophagus were clear in 50 healthy controls,and the esophageal hiatus diameters were (1.96±0.39) cm.In contrast,the cardiac and abdominal esophagus in EHH patients were unable to be identified in subdiaphragm region.The esophageal hiatus was wider with a diameter of (3.24±0.76) cm.The difference was statistically significant(t=2.36,P＜0.05).The hernia sacs were found in 78 EHH patients at rest.And the hernia sacs were present on the diaphragm in 10 EHH patients after pressure.The maximum diameter of hernia sac was 7.6 cm.The size of hernia sac may change with abdominal pressure.In sliding EHH patients,the sac wall was found to slide up and down the diaphragm.A mass was found on the wall in 2 patients.The B ring was present in 76 patients.For healthy controls in supine position,contrast-enhanced ultrasound showed that the gastric bottom and diaphragm were at dependent or horizontal position.The gastric bottom and diaphragm was upward in 73 patients.Conclusions The EHH has characteristic appearance on CEUS.It is easy to detect and diagnose EHH with CEUS,which has a diagnostic value in detection of space-occupying lesions in hernia sac.CEUS can be used for EHH screening.

AIM: To investigate the mechanism of proliferation effect induced by (R,R)-XY-10 and (S,S)-XY-10 on retinal pigmented epithelial cells(ARPE-19).METHODS: Human retinal pigmented epithelial cells(ARPE-19) and human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of (R,R)-XY-10 and (S,S)-XY-10 on cell growth,and their mechanisms of proliferative action by using ERK、 AKT、PI3K、Protein kinase C (PKC)and Nitric oxide synthase (NOS) inhibitors.RESULTS: (R,R)-XY-10 and (S,S)-XY-10 dose-dependently increased ARPE-19 cell proliferation,but not on HUVECs. When treated with proliferative inhibitors,H7(5μmol/L)、hypericin(20μmol/L)、PD98059(2μmol/L)、LY294002(50μmol/L)、SH-5 (10μmol/L) and L-NAME (100μmol/L),the proliferative effect was reduced by H7、hypericin、PD98059 and LY294002,but not by SH-5 and L-NAME.CONCLUSION: (R,R)-XY-10 and (S,S)-XY-10 can induce cell proliferation through MAPK and PI3K dependent pathway. KEYWORDS: age-related macular degeneration; (R,R)-XY-10; (S,S)-XY-10; ARPE-19 cells; human umbilical vein endothelial cells; proliferation

Objective To observe the clinical effect of neonatal respiratory failure therapy with mechanical ventilation. Methods Forty - eight cases of neonatal respiratory failure were applied endotracheal intubation through mouth. At first, ventilation was given via the intermittent positive - pressure ventilation + peak end - expiratory pressure( IPPV + PEEP) way. Later, the breath parameters were regulated and transited to the intermittent mandatory ventilation( IMV) way according to original illness. When frac - tional concentration of in-spired gas(FiO2)

Objective To explore the incidence and distribution features of neonatal phenylketonuria(PKU) and congenital hypothyroidism(CH) in Lianyungang area.Methods The heel blood samples dried on filter paper was collected from newborns after 72 hours.As the screening indicators,PKU was detected through serum phenylalanine concentration(Phe) detection by Guthrie′s bacterial inhibition assay and CH was detected through serum thyroid stimulating hormone(TSH) levels detection by time-resolved fluorometry(TRFIA) or enzyme linked immunosorbent assay(ELISA).Results Sixty-four children with CH were diagnosed and the rate of CH was 1∶2423,41 patients were examined by thyroid gland nuclein kinescope picture,among which there were 23 patients whose thyroid glands were unusal.These patients lived in 45 towns(streets),which had no difference between men and women,city and country side.A couple of twins were screened for CH;15 cases of PKU was detected with an incidence of 1∶10 339.These patients′ parents were neither consanguineous marriage nor dominance hereditary family history.Their physical and mental development were similar to the same age children after interventive treatment.Conclusions The distribution of CH and PKU is diffuse in Lianyungang.Neonatal screening is the only valid means to find patients with CH and PKU.

BACKGROUND:Numerous studies have demonstrated that estrogen can regulate the proliferation and migration of endothelial progenitor cel s (EPCs), while EPCs can also promote the function and activity of bone marrow mesenchymal stem cel s (BMSCs) in vitro. OBJECTIVE:To evaluate the ability of the BMSCs and EPCs which construct the composite cel sheet in the repair of alveolar bone defect in ovariectomized rats. METHODS:BMSCs/EPCs composite sheet, EPCs sheet and BMSCs sheet were respectively implanted into the defects of the alveolar bone in ovariectomized rats. Rats with no implantation served as control group. Repaired alveolar bone was assessed by gross examination, histological observation and micro-CT scan at 2, 4, 8 weeks after operation. RESULTS AND CONCLUSION:BMSCs/EPCs composite sheet has greater osteogensis activity and bone repair capacity than BMSCs or EPCs sheet alone.