Choroid neovascularization (CNV) is pathological proliferation of choroid vascular,accompanying with bleeding and leakage,is one of the major factors caused blindness,so CNV inhibitors have become a research hotspot.At present,researches on inhibitors of vascular endothelial growth factors and their receptors,endogenous angiogenesis factors,redox and inflammatory response related factors,etc,have achieved certain progresses.In addition,as drugs with multiple targets for treatment,many Chinese herbs also show inhibition effect on CNV.This article reviews the research advances in inhibitors for CNV.

Objective To explore the relationship between disorders of lipid metabolism and avascular necrosis of femoral head after operation of femoral neck fracture .Methods 160 patients with a diagnosis of fresh femoral neck fractures treated with AO cannulated compressed screws in orthopedic department of our hospital from January 2007 to January 2012 were involved .All the patients were divided into two groups :ANFH or non ANFH group according to the features of femoral head .The levels of blood lipid were examined .Then ,Logistic regression was used to screening risk factors and evaluate the influence of blood lipid factors ac-cording to βrisk factor .Results The levels of TC ,TG ,LDL and Apo B in ANFH group were (5 .99 ± 1 .05)mmol/L ,(2 .63 ± 0 .85)mmol/L ,(4 .16 ± 1 .21)mmol/L ,(0 .99 ± 0 .28)g/L respectively ,which increased remarkably compared with the control group ;while HDL ,Apo A1 levels in the ANFH group were (0 .88 ± 0 .19)mmol/L ,(1 .20 ± 0 .17)g/L ,which was remarkably lower compared with the control group ,and there were statistically significant difference (P=0 .000) .Serum TC and LDL levels were risk factors impacted on postoperative ANFH .Conclusion Postoperative ANFH was related to disorders of lipid metabolism .Serum TC and LDL levels could be diagnostic values on postoperative ANFH .Early control of blood lipid levels may prevent the development of ANFH in patients treated with AO cannulated compressed screws .

cuses tumors. Survivin seems to be a promising marker for analyzing clinical stages and predicting the prognosis of TCC.

Objective To investigate and compare the action of curcuminoids on the causal pathogens of Candida albicans growth.Methods The effects of curcumin (CUR) and demethoxycurcumin (DMC) on C.albicans growth were first investigated and compared by microcalorimetry coupled with multiple analytical methods.The quantitative thermo-kinetic parameters obtained from these curves were analyzed to show difference of the actions.Results By analyzing the main parameters screened from principal component analysis together with 50％ inhibiting concentration values,it was demonstrated that both CUR and DMC showed good antifungal activities and CUR was stronger.It was further concluded from structure-activity relationship that the existence of methoxy group might enhance lipophilicity of the mother nucleus,which made it easier for the molecular to enter into the cell membrane of fungi to inhibit its growth.Conclusion This study provides a new method for screening new antifungal agents with high efficacy and low toxicity.Meanwhile,it contributes to the application of curcuminoids as food additive,colorant,and drug.Microcalorimetry is real-time,online,and dynamic,and it could be used to characterize the subtle difference among the effects of synthetic and natural products on the vital process of fungi.

Objective To investigate the role of T helper 17 cells/interleukin?17(Th17/IL?17) axis in the occurrence of vaginal candidiasis in mice. Methods A total of 120 female BALB/c mice were randomly and equally divided into Ei, En, Ci and Cn groups. Three days before vaginal inoculation, estrogen (Ei and En)groups and control(Ci and Cn)groups received subcutaneous injection of 0.05 mg estradiol and 0.1 ml sterilized soybean oil at the hind legs, respectively, and then the hormone treatment continued every other day until the end of experiment. Infected(Ei and Ci)groups and noninfected(En and Cn) groups were inoculated intravaginally with 10μl(5 × 104 conidia)of Candida albicans suspension and 10μl of sterilized phosphate?buffered saline, respectively. Ten mice were randomly selected from each group and sacrificed on day 3, 7 and 14 after inoculation. The intact vagina tissues were resected and then frozen in liquid nitrogen or embedded in paraffin. Real?time fluorescence?based quantitative PCR(qRT?PCR)and immunofluorescent staining were performed to measure mRNA expression and immunofluorescence intensities of retinoic acid?related orphan receptorγt(RORγt), RORα and IL?17, respectively. Western blot analysis was conducted to determine protein expression of RORγt and IL?17. Results Laser scanning confocal microscopy showed that RORγt, RORα and IL?17 immunofluorescence was mainly located at inflammatory cells of the lamina propria and blood vessels in En and Cn groups, at mucosal epithelium, adherent hyphae, and inflammatory cells of the lamina propria and blood vessels in Ci group, and at mucosal epithelium, vaginal canal and endocytosed hyphae, and inflammatory cells of the lamina propria and blood vessels in Ei group. qRT?PCR and immunofluorescent staining uncovered that mRNA expression and immunofluorescence intensities of RORγt, RORα and IL?17 were significantly higher in En, Ci and Ei groups than in Cn group at the same time points(all P<0.05), as well as in the Ei group than in En and Ci groups(both P<0.05), and were increased gradually over time in En, Ci and Ei groups, but not in the Cn group. Additionally, mRNA expression and immunofluorescence intensities of RORγt and RORαand IL?17 generally peaked on day 14 after inoculation, while the immunofluorescence intensity of IL?17 peaked on day 7 (P < 0.05). Western blot analysis revealed that protein expression of RORγt and IL?17 was significantly higher in the infected(Ei and Ci)groups than in the noninfected(En and Cn)groups at the same time points(RORγt:F=45.685, P<0.001;IL?17:F=29.655, P<0.01), and was highest in the Ei group(P<0.05);however, no significant differences were observed between Cn and En groups(both P>0.05). Moreover, RORγt and IL?17 protein expression in Ci and Ei groups was obviously up?regulated on day 7 after inoculation (RORγt: F = 13.137, P < 0.001; IL?17: F = 11.182, P < 0.001), but was not increased further on day 14. Conclusion Vaginal candida infection can up?regulate the expression of RORγt, RORα and IL?17, suggesting that Th17/IL?17 axis may be involved in the occurrence of vaginal candidiasis in BALB/c mice.

Objective To evaluate the efficacy and safety of focal fractional laser treatment(FFLT)for atrophic acne scars. Methods A randomized, self-controlled study was performed. A total of 20 patients with atrophic facial acne scars were enrolled into this study. Treatments were randomly administered in a split-face manner. Half of each subject′s face received FFLT(FFLT side), and the other half underwent full-face fractional CO2 laser resurfacing(control side), for one session. All the patients were followed up for 3 months after the treatment. Evaluation was based on the ECCA grading scale (échelle d′évaluation clinique des cicatrices d′acné)and patient satisfaction score. A VISIA skin detector was used to take photographs and evaluate skin texture. Moreover, physical parameters of the skin, including erythema index, melanin index and transepidermal water loss (TEWL), were measured. Adverse effects were recorded and evaluated. Statistical analysis was carried out by paired t test, Wilcoxon paired rank test, Fisher′s exact test and repeated-measure analysis of variance. Results The ECCA score decreased from 51.24 ± 17.61 at the baseline to 34.46 ± 14.99 at 3 months after the treatment at the FFLT side(t = 7.886, P < 0.05), and from 50.96 ± 18.96 to 38.29 ± 14.86 at the control side(t =6.123, P < 0.05), and was significantly lower in the FFLT side than in the control side (t = 4.462, P < 0.05)at 3 months after the treatment. The improvement rate was significantly higher in the FFLT side than in the control side (32.75% vs. 24.86%, P = 0.016 by Fisher′s exact test)at 3 months after the treatment. Decreased pain and edema scores were observed at the FFLT side compared with the control side at 1 hour after the treatment (both P < 0.05), but no significant difference was noted in the duration of erythema or crusting between the two sides (both P > 0.05). Compared with those before the treatment, skin texture scores decreased in both sides (both P < 0.05), and were significantly lower in the FFLT side than in the control side at 3 months after the treatment(P < 0.05). The erythema index was significantly lower in the FFLT side than in the control side in both scarred areas and non-scarred areas on day 1 after the treatment (both P < 0.05). Both melanin index and TEWL at the FFLT side were significantly increased in scarred areas, but decreased in non-scarred areas compared with those at the control side within 3 days after the treatment (all P < 0.05). Similarly, the water content of the stratum corneum at the FFLT side was significantly lower in scarred areas, but higher in non-scarred areas compared with that at the control side between day 1 and 7 after the treatment (both P < 0.05). No significant difference was observed in the erythema index, TEWL or water content of the stratum corneum between the FFLT side and control side at scarred areas or non-scarred areas(all P > 0.05)from 2 weeks to 3 months after the treatment(all P > 0.05). Conclusion FFLT can improve therapeutic outcomes in atrophic acne scars with reduced adverse reactions.

Inflammatory bowel disease (IBD) is a chronic recurrent non-specific inflammatory disease in the intestinal tract. About 10%-56% of children with Crohn's disease and about 10% of children with ulcerative colitis have growth retardation. This study reports four adolescents with IBD and growth hormone deficiency who were diagnosed with Crohn's disease. There were three boys and one girl, with an age of 11.0-13.9 years and a disease duration of 11-85 months at diagnosis. The four patients had the involvement of the small intestine only, the colon only, both the small intestine and the upper gastrointestinal tract, and both the small intestine and the colon respectively. The pediatric Crohn's disease activity index ranged from 27.5 to 45 points. All four patients had a height-for-age Z-score (HAZ) of <-2, and the growth hormone provocative test suggested growth hormone deficiency. Of all four patients, two received recombinant human growth hormone combined with infliximab, one received infliximab only, and one received recombinant human growth hormone combined with mercaptopurine. All four patients had an improvement in HAZ after treatment.
Adolescent ; Child ; Colitis, Ulcerative ; Crohn Disease ; Female ; Growth Hormone ; Humans ; Inflammatory Bowel Diseases ; Infliximab ; Male

OBJECTIVETo study changes of glycolipid metabolism and adipocyte function in an catch-up growth intrauterine growth retardation (IUGR) rat model.

METHODSIUGR rat model was established by maternal nutrition restriction during pregnancy. Newborn IUGR pups were used as IUGR group, and normal newborn pups were used as control group (appropriate for gestational age, AGA group). At age of 12 weeks, plasma samples were collected for the test of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), adiponectin and acylation stimulating protein (ASP). Oral glucose tolerance test (OGTT) was performed for the test of glucose and insulin levels, and insulin resistance index (IRI) was calculated. Expression of glucose transfer 4 (GLUT-4) in adipocytes was examined by confocal microscopy.

RESULTSBody weight and BMI in the IUGR group were significantly higher than in the AGA group by 12 weeks (P<0.01), and plasma TC, TG and LDL-C levels in the IUGR group were higher than in the AGA group, but HDL-C was lower (P<0.05). In the OGTT test, blood glucose level and IRI score in the IUGR group were higher than in the AGA group (P<0.05). Compared with the AGA group, the IUGR group had a higher ASP level (P<0.05) and a lower adiponection level (P<0.05). GLUT4 expression in the adipocytes was significantly lower in the IUGR group than in the AGA group (P<0.05).

CONCLUSIONSCatch-up growth may be obviously noted in IUGR rats after birth. Both hyperlipidaemia and insulin resistance occur at age of 12 weeks. Dysfunction of adipocytes decreased expression of GLUT-4 may be risk factors for insulin resistance in IUGR rats.

Adipocytes ; physiology ; Animals ; Blood Glucose ; analysis ; Body Mass Index ; Body Weight ; Carbohydrate Metabolism ; Female ; Fetal Growth Retardation ; physiopathology ; Glucose Transporter Type 4 ; analysis ; Lipid Metabolism ; Male ; Rats ; Rats, Sprague-Dawley

AIMTo explore whether the anti-tumor action of 17beta-estradiol is enhanced by re-expression of the homeodomain transcription factor Nkx3.1 in PC3 human prostate cancer cells.

METHODSPC3 cells were stably transfected with pcDNA3.1-Nkx3.1-His vector, which carries a full-length cDNA of human Nkx3.1. The PC3 cells stably transfected with vector pcDNA3.1 were set as a control. The expression of Nkx3.1 protein in the cells was confirmed by Western blot analysis. The effect of Nkx3.1 on cell proliferation of PC3 cells was examined with MTT assay. The antiproliferative and apoptotic effects of 17beta-estradiol alone or in combination with Nkx3.1 were estimated on PC3 cells by using MTT growth tests and flow cytometric analyses. The expression of apoptosis-related proteins was analyzed using Western blotting.

RESULTSThe plasmid carrying Nkx3.1 gene induced high expression of Nkx3.1 protein in PC3 cells. The re-expression of exogenous Nkx3.1 did not cause a significant reduction in cellular proliferation, whereas the expression of Nkx3.1 enhanced the 17beta-estradiol anti-proliferative effect in PC3 cells. Nkx3.1 expression promoted 17beta-estradiol-induced apoptosis of PC3 cells, as shown by analysis of Bcl-2, Bax, Caspase-3 and poly (ADP-ribose) polymerase expression.

CONCLUSIONThe present study demonstrates that re-expression of Nkx3.1 enhances 17beta-estradiol anti-tumor action in PC3 human prostate cancer cells. The in vitro study suggests that re-expression of Nkx3.1 is worthy of further consideration as an adjuvant treatment of androgen independent prostate cancer with estrogen anti-tumor therapies.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Androgen-Insensitivity Syndrome ; drug therapy ; genetics ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Estradiol ; pharmacology ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; drug effects ; genetics ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; genetics ; pathology ; Transcription Factors ; genetics ; metabolism ; Transfection

OBJECTIVEThis study examined the effects of PI3K inhibitor LY294002 on the differentiation of mouse preadipocytes and the expression of CCAAT enhancer binding protein α (C/EBPα) and peroxisome proliferation activated receptor γ (PPARγ), in order to study the possible roles of insulin receptor substrate (IRSs)/PI3K signal pathway in the differentiation of preadipocytes.

METHODSThe mouse 3T3-L1 cells were cultured normally and divided into experimental and control groups. 3T3-L1 cells in the experimental group were treated with PI3K inhibitor LY294002 (25 μmol/L) and those in the control group were treated with DMSO culture medium. 3-isobutyl-1-methylxanthine (IBMX) (0.5 mmol/L), dexamethasone (10-6 mol/L) and insulin (5 μg/mL) were used to induce the differentiation of 3T3-L1 preadipocytes in both groups. Before culture, and 2, 4 and 8 days after culture, the cells were collected to detect the expression of C/EBPα and PPARγ by real-time PCR and Western blot assays. The lipid droplets of 3T3-L1 preadipocytes were observed by oil-red O staining.

RESULTSPI3K inhibitor LY294002 did not affect the expression of C/EBPα and PPARγ in un-induced 3T3-L1 preadipocytes (P>0.05), but decreased the expression of C/EBPα and PPARγ during the in vitro induced differentiation of 3T3-L1 preadipocytes compared with the control group (P<0.05 or 0.01). The lipid droplets count was greatly reduced by LY294002.

CONCLUSIONSPI3K inhibitor LY294002 can inhibit the differentiation of mouse 3T3-LI preadipocytes and the expression of C/EBPα and PPARγ in the differentiation of 3T3-LI preadipoeytes, suggesting that IRSs/PI3K signal pathway may play an important role in the differentiation of 3T3-L1 preadipocytes by regulating the expression of C/EBPα and PPARγ.

3T3-L1 Cells ; Adipocytes ; cytology ; drug effects ; Animals ; CCAAT-Enhancer-Binding Protein-alpha ; analysis ; genetics ; Cell Differentiation ; drug effects ; Chromones ; pharmacology ; Gene Expression Regulation ; drug effects ; Mice ; Morpholines ; pharmacology ; PPAR gamma ; analysis ; genetics ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; RNA, Messenger ; analysis