AlM: To investigate the efficacy of photodynamic therapy ( PDT) and intravitreal injection with ranibizumab on macular choroidal neovascularization ( CNV ) of pathologic myopia ( PM) .
METHODS: There were patients ( 32 eyes ) who were diagnosed as PM with CNV. Randomly selected 16 cases ( 16 eyes ) which were given the PDT treatment ( PDT group ) . The remaining were given both PDT and intravitreal injection with ranibizumab ( combination group) . There is no significant difference on macular edema between two groups. We analyzed the changes in the best corrected visual activity ( BCVA) , optic coherence tomograph ( OCT ) and fundus fluorescein angiography (FFA) before and 1, 6mo after treatment.
RESULTS:One month after the treatment in PDT group:the BCVA increased while the CMT decreased compared with that of pretreatment (P<0. 05). One month after the treatment in combination group: the BCVA increased while the CMT decreased significantly compared with that of pretreatment (P<0. 01);the changes of BCVA and CMT showed statistically significant between the two groups ( P<0. 05). Six month after the treatment in PDT group: the BCVA increased while the CMT decreased compared with that of pretreatment ( P <0. 05 ). Six month after the treatment in combination group: the BCVA increased while the CMT decreased significantly compared with that of pretreatment ( P <0. 01 ); compared with changes of BCVA and CMT in two groups, the difference was significant after treatment (P<0. 05). Compared 1mo with 6mo after treatment:there was no significant difference in the BCVA and CMT changes (P>0. 05). One month after treatment: in PDT group, FFA showed no leakage or reduced leakage of CNV in 11 eyes (69%), and the fundus remained leaky in 5 eyes ( 31%); in combination group, FFA showed no leakage or reduced leakage of CNV in 13 eyes (81%);the fundus remained leaky in 3 eyes (19%). Six month after treatment:in PDT group, FFA showed no leakage or reduced leakage in 10 eyes ( 62. 5%); the fundus remained leaky in 4 eyes ( 25%); two eyes ( 12. 5%) relapsed leakage; in combination group, FFA showed no leakage or reduced leakage of CNV in 15 eyes (94%);the fundus remained leaky in 1 eye (6%).
CONCLUSlON: Not only PDT but also PDT and intravitreal injection with ranibizumab can block CNV of pathologic myopia completely or partly, and reduce the danger causing descent of vision. Effects and the stability of the combination therapy is superior to PDT treatment.

Objective:To study the antiviral effect of ISG20 on HCV replicon.Methods:Wild type ISG20/mutated ISG20 cDNAs were obtained by RT-PCR/two step-PCR directed mutagenesis, and wild type ISG20 and dominant negative mutated ISG20 mammal expression vectors were consuructed. The constructed pISG20wt and pISG20m expressing vectors were transfected into Huh7 cells or Huh7 cells containing HCV replicon to investigate its effects on HCV replicon replication.Results:The ISG20wt/ISG20m expression vectors were constructed and the expressions of these two vectors were confirmed at both mRNA and protein levels. The effects of ISG20wt on HCV replicon replication were evaluated by Northern blot and Western blot. The results showed that expression of ISG20wt had significant inhibitory effect on HCV RNA replication.Conclusion:ISG20 participates in the anti-HCV action of IFN-? on HCV replicon system.

Objective Through the evaluation of acute myocardial infarction patients care burden of caregivers,to understand caregiver stress con?dition,and to investigate the effective predictors of acute myocardial infarction patients care burden of caregivers,so as to provide the basis for im?provement of the care burden. Methods A cross?sectional study was conducted through convenience sampling using Zarit Caregiver Burden Inter?view as the measuring tool. Questionnaires were collected by face?to?face structured interviews towards caregivers. Care burden of caregivers was eval?uated on these primary caregivers of patients with acute myocardial infarction. Results Caregivers of patients with myocardial infarction endure high care burden level. There were statistically significance among patients with different ages or revenue,the relationship of caregivers with patients,nurs?ing hours per day,psychological alignment and patients′self?care ability. Conclusion Caregivers of patients with myocardial infarction endure high care burden level. The relationship between caregivers and patients,the patient′s gender,nursing total time,nursing time every day,and the pa?tient's life self?care ability are contributed to be predictive factors. Future interventions should be strengthen on the psychological ability of the align?ment as well as measures to improve the self?care ability of the patient's life.

Objective To explore the value of 18 F-fluorodeoxyglucose (i8 F-FDG) PET/CT examination in the differential diagnosis of the gastric cancer and primary gastric lymphoma (PGL).Methods The clinical data of 80 patients with gastric cancer (60 with non-mucinous adenocarcinoma and 20 with mucinous adenocarcinoma) and 47 patients with PGL [22 with mucosa-associated lymphoid tissue (MALT) and 25 with diffuse large B-cell lymphoma (DLBCL)] who were admitted to the Tianjin Medical University Cancer Institute and Hospital from June 2006 to May 2014 were retrospectively analyzed.Spiral CT scan was first done and then followed by PET.The CT value of the lesions,maximum standardized uptake value (SUVmax) of patients and maximal gastrointestinal wall thickness (THKmax) were analyzed by the ANOVA test.The SUVmax comparison between groups was evaluated with the Student-Newman-Keuls.The lesions type was analyzed by the chi-square test.The THKmax and SUVmax among groups were analyzed by the Pearson correlation analysis.Results 18 F-FDG PET/CT imaging of patients with gastric cancer and PGL showed different types of gastric wall thickening,segmental and limited thickening of gastric wall were the main features of gastric cancer and diffuse and segmental thickening of gastric wall were the main features of PGL.The type Ⅰ,Ⅱ and Ⅲ of lesions were detected in 12,21 and 27 of 60 patients with nonmucinous adenocarcinoma,in 2,7 and 11 of 20 patients with mucinous adenocarcinoma,in 8,8 and 6 of 22 patients with MALT and in 13,7 and 5 of 25 patients with DLBCL respectively.There were significant differences in the 4 pathological types of lesions among all the patients (x2 =14.849,P ＜ 0.05).The lymph nodes beneath the renal hilum and at the retroperitoneum were involved in 16 patients with gastric cancer and in 10 patients with PGL,and 7 patients with gastric cancer and 12 patients with PGL were complicated with splenomegalia,respectively,showing a significant difference in the splenomegalia between patients with PGL and gastric cancer (x2=7.506,P ＜0.05).There was no significant difference in the metastasis of lymph nodes beneath the renal hilum and at the retroperitoneum between patients with PGL and gastric cancer (x2=0.178,P ＞0.05).Among 80 patients with gastric cancer,positive 18F-FDG was detected in 79 patients and negative 18F-FDG in 1 patient with T3 stage of mucinous adenocarcinoma.Among 47 patients with PGL,positive 18 F-FDG was detected in 46 patients and negative 18F-FDG in 1 patient with stage Ⅰ of MALT.The CT value of the lesion,SUVmax and THKmax in patients with non-mucinous adenocarcinoma,mucinous adenocarcinoma,MALT and DLBCL were (40 ± 8)HU,(39±11)HU,(41±11)HU,(38±9)HU and 9.9 ±6.6,5.6±1.9,4.6 ±2.9,18.3±7.6 and (2.1 ± 1.2) cm,(1.9 ± 0.9) cm,(1.3 ± 1.1) cm and (2.6 ± 1.5) cm,respectively,showing significant differences in the SUVmax among all the groups (F =26.920,P ＜ 0.05).In the pairwise comparisons,there were no significant difference between the MALT group and mucinous adenocarcinoma group (P ＞ 0.05),and significant differences among the other groups (P ＜ 0.05).The CT value of the lesions and THKmax among all the patients were compared,with no significant differences (F =0.578,4.510,P ＞ 0.05).There were no significant differences in the SUVmax and THKmax among all the patients (r =0.055,0.346,0.226,0.133,P ＞ 0.05).Conclusions There is an important diagnosis value of PET/CT examination in patients with gastric cancer and PGL.The pathological types of the lesions in patients with gastric cancer and PGL are different.The occurrence of splenomegalia in patients with PGL is easier than that with gastric cancer.SUVmax of patients with DLBCL is higher than those with gastric cancer and MALT.FDG uptake in patients with mucinous adenocarcinoma and MALT are not enough,and these may lead to false negative result of PET/CT examination.

Objective: Lung metastases are common in patients with differentiated thyroid carcinoma (DTC). Post-therapeutic 131I-whole-body scan (WBS) was conventionally administered after the radioactive iodine treatment (RAI) of DTC lung metastases. This study aimed to investigate the influencing factors of WBS imaging on the RAI of DTC lung metastases. Methods:DTC patients (n=60) with lung metastases treated with 131I were retrospectively included. Before treatment, the thyroid function was assessed. Neck and chest computed tomography (CT) was performed, and WBS was inspected. Patients with lung metastases were classified into negative and positive subgroups according to the imaging of 131I WBS, and the relative influencing factors were analyzed. Results:Univariate analy-sis showed that age and chest CT imaging, which revealed pulmonary fibrosis, calcification, and patchy shadows, were related to WBS imaging. Binary variable logistic regression analysis revealed that pulmonary fibrosis (OR=0.175, P<0.001) and calcification (OR=0.088, P<0.05) went against the development of WBS. Conclusion:WBS imaging on RAI of lung metastases was not obvious in the el-derly. The fibrosis, calcification, and patchy shadows of the lung were not conducive for WBS imaging. The fibrosis and calcification of the lung were the main factors that affect WBS imaging.

Adult ; Female ; Humans ; Nasal Mucosa ; pathology ; Nose Neoplasms ; diagnosis ; surgery ; Papilloma ; diagnosis ; surgery

Objective To investigate the effects of p300/CBP on histone acetylation of Foxp3 gene and its roles in the immunological pathogenesis of Kawasaki disease (KD).Methods Forty-six children with KD and twenty-eight age-matched health children were consented to participate in this study.Co-immunoprecipitation and real-time PCR were performed to detect Foxp3-associated acetylation levels of histone H4 and binding abilities of p300, CBP, pSmad3 (phosphorylated mothers against decapentaplegic homolog 3) and NF-AT (nuclear factor of activated T cells) with Foxp3 gene in CD4+ T cells.The percentages of CD4+CD25high Foxp3+ cells (Treg) and the expression of Foxp3, CTLA4 (cytotoxic T-lymphocyte-associated protein 4), p300, CBP, TGF-βRⅡ (transforming growth factor β receptor Ⅱ) and pLAT1 at protein level were analyzed by flow cytometry.Quantitative real-time PCR was used to measure the expression of Foxp3, IL-10, TGF-β, TGF-βRⅠ, Egr-1 (early growth response protein 1), RARα (retinoic acid receptor α) and PLCγ1 (phospholipase C-γ1) in Treg cells at mRNA level.Plasma concentrations of TGF-β and retinol acid (RA) were measured by enzyme-linked immunosorbent assay.Results (1) The percentages of Treg cells, levels of Foxp3 and molecules associated with suppressive function of Treg cells (TGF-β, IL-10 and CTLA4), acetylation levels of histone H4 associated with promoter, conserved non-coding DNA sequence 1 (CNS1) and CNS2 of Foxp3 gene decreased remarkably during acute KD (P<0.05), but were restored after IVIG therapy (P<0.05).Meanwhile, all of the aforementioned items in KD patients with coronary artery lesions (KD-CAL+) were lower than those without coronary artery lesions (KD-CAL-) (P<0.05).No significant differences in histone H4 acetylation associated with CNS3 were found among different groups (P>0.05).(2) The levels of p300 and CBP in Treg cells and their binding abilities with Foxp3 gene were down-regulated significantly during acute KD (P<0.05), but were restored to some extent after IVIG treatment (P<0.05).The Foxp3-associated histone acetylation was positively correlated with the expression of p300 and CBP at mRNA level during acute KD (r=0.65, 0.42, P<0.05).Furthermore, the expression of p300 and CBP and their binding abilities with Foxp3 gene in KD-CAL+ group were lower than those in KD-CAL-group (P<0.05).(3) Compared with healthy subjects, plasma concentrations of TGF-β and RA and the expression of TGF-βRⅠ/Ⅱ/Egr-1, RARα and pLAT1/PLCγ1 were down-regulated during acute KD (P<0.05);the binding abilities of pSmad3 and NFAT with Foxp3 gene were reduced remarkably in patients with acute KD (P<0.05).All the items mentioned above were restored after IVIG treatment (P<0.05).Moreover, the ten items aforementioned in KD-CAL+ group were lower than those in KD-CAL-group (P<0.05).(4) Higher acetylation levels of histone H4 associated with promoter, CNS1 and CNS2, and enhanced binding abilities of p300 and CBP with Foxp3 gene were found in CD4+ T cells isolated from patients with acute KD after co-stimulation with TGF-β, RA and anti-CD3/CD28 antibodies as compared with those in CD4+ T cells without stimulation (P<0.05).However, no statistical difference in the acetylation level of histone H4 associated with CNS3 was found between the two groups (P>0.05).Conclusion Hypoacetylation of histone H4 associated with Foxp3 gene caused by insufficient expression of p300/CBP and their impaired binding abilities might be involved with immune dysfunction in KD.IVIG therapy regulates the expression of p300/CBP and their binding abilities with Foxp3 gene through up-regulating TGF-β signal.

Objective To investigate the effects of SMYD3 and MLL5 on histone methylation of Transcription factor forkhead box protein 3 (Foxp3) gene and its roles in the immunological pathogenesis of Kawasaki disease (KD). Methods Forty-two children with KD and 26 age-matched healthy children were consented to participate in this study. Co-Immunoprec-ipitation and real-time polymerase chain reaction (PCR) was performed to determine Foxp3-associated histone methylation levels of H3K4me3 and H3K27me3, and binding levels of SMYD3 and MLL5 with Foxp3 gene in CD4+T cells. The proportion of CD4+CD25high Foxp3+cells (Treg) and protein levels of Foxp3, cytotoxic T lymphocyte associated antigen-4 (CTLA4), TGF-βRⅡand pSmad3 were analyzed by flow cytometry. Quantitative real-time PCR was used to evaluate levels of Foxp3, interleukin (IL)-10, GITR, TGF-βRⅠand RARαmRNA in CD4+T cells. Plasma concentrations of TGF-βand retinol acid (RA) were measured by enzyme-linked Immunosorbent assay. Independent-samples t-test was used as the statistical method in this study. Results ① The proportion of Treg, expression levels of Foxp3 and molecules associated with suppressive function of Treg cells(IL-10, GITR and CTLA4), and histone methylation levels of H3K4me3 associating with promoter, conserved non-coding DNA sequence (CNS) 1 and CNS2 of Foxp3 gene decreased remarkably during acute KD [Promoter:(5.4±1.8)%vs (9.1±2.2)%;CNS1:(2.6±0.9)% vs (3.8±1.1)%; CNS2: (2.4±0.8)% vs (4.2±1.0)%; t=5.50, 6.02, 9.56, 7.92, 7.97, 4.76, 7.73, 5.01, 8.66; P<0.05], and restored after intravenous immunoglobulins (IVIG) therapy [Promoter: (7.2 ±2.1)% vs (5.4 ±1.8)%; CNS1:(3.6±1.4)% vs (2.6±0.9)%; CNS2: (3.6±1.4)% vs (2.4±0.8)%; t=5.56, 4.59, 7.01, 6.04, 5.89, 4.83, 4.45, 4.00, 5.12; P<0.05]. Meanwhile, the nine former items in KD patients with coronary artery lesions (KD-CAL+) were lower than those without coronary artery lesions (KD-CAL-) [Promoter: (4.11±1.45)% vs (6.16±1.93)%; CNS1:(1.99±0.87)%vs (2.96±1.10)%;CNS2: (1.75±0.63)%vs (2.72±1.16)%;t=6.28, 3.24, 4.56, 3.69, 3.38, 4.40, 3.65, 3.00, 3.51; P<0.05]. No significant difference of H3K4me3 associated with CNS3 and H3K27me3 were found among the groups (t=1.03, 0.91, 1.48 and 0.79, 0.82, 1.53; P>0.05). ② Binding levels of SMYD3 and MLL5 with Foxp3 gene in CD4+T cells were down-regulated significantly during acute KD (t=6.63, 6.15; P<0.05), and restored to some extent after IVIG treatment (t=5.36, 4.56; P<0.05). Positive correlations between binding levels of SMYD3 and MLL5 and expression level of Foxp3 mRNA were detected in patients with acute KD (r=0.62、0.45, P<0.05). Furthermore, Binding levels of SMYD3 and MLL5 with Foxp3 gene in KD-CAL+group were lower than those in KD-CAL- group (t=4.11, 4.31; P<0.05). ③ Compared with healthy controls, plasma concentration of TGF-β and RA, and expressions of TGF-βRⅡ, TGF-βRⅠ, pSmad3 and RARα were down-regulated during acute KD (t=11.54, 12.81, 7.43, 16.10, 8.25, 12.06; P<0.05), and elevated remarkably after IVIG treatment (t=8.40, 6.24, 5.94, 11.78, 6.27, 8.30; P<0.05). Simultaneously, all the items aforementioned in KD-CAL+ group were found to be lower than those in KD-CAL-group (t=3.58, 3.30, 3.82, 5.27, 4.71, 3.78; P<0.05). Conclusion Hypomethylation of H3K4me3 associated with Foxp3 gene caused by insufficient binding levels of SMYD3/MLL5 may be involved with immune dysfunction in Kawasaki disease.

Objective To investigate the changes and significances of IL-17-associated histone methylation in the acute phase of Kawasaki disease (KD). Methods Forty-two children with KD and 28 age-matched healthy children were recruited in this study. Co-immunoprecipitation and real-time PCR were performed to detect the IL-17-associated histone methylation in CD4+ T cells. The percentages of CD4+IL-17+ T cells (Th17) and the expression of IL-17 and pSTAT3 at protein level were analyzed by flow cytome-try. Quantitative real-time PCR was used to measure the expression of IL-17, IL-6Rα, gp130, IL-23R, IL-23Rβ1, ETV5, SOCS1, SOCS3, TLR4, MyD88/TRIF, TNFR1 and RIP1 at mRNA level and the expres-sion of miR155 in CD4+ T cells. The levels of IL-6, IL-23 and TNF-αin plasma samples were measured by enzyme-linked immunosorbent assay. Results (1) The children with acute KD showed increased percenta-ges of Th17 cells and enhanced expression of IL-17 and H3K4me3, but inhibited expression of H3K27me3 [H3K4me3:(3.79±1. 45)% vs (1. 93±0. 31)%, H3K27me3: (54. 51±13. 60)% vs (73. 96± 22. 32)%;P<0. 05]. Moreover, the three former indexes in KD patients complicated with coronary artery lesions ( KD-CAL+) were higher than those in KD patients without coronary artery lesions ( KD-CAL-) , while the levels of H3K27me3 in KD-CAL+ group were lower than those in KD-CAL- group [ H3K4me3:(5. 11±1. 68)% vs (2. 98±0. 99)%, H3K27me3:(45. 02±14. 83)% vs (60. 35±12. 51)%;P<0. 05]. A positive correlation was observed between the ratio of H3K4me3/H3K27me3 and IL-17 at transcriptional level in patients with acute KD (r=0. 69, P<0. 05). Treatment with intravenous immunoglobulin (IVIG) restored Th17 cells, expression of IL-17 and methylation levels of H3K4me3 and H3K27me3 to normal levels [H3K4me3:(2. 44 ± 0. 77)% vs (3. 79 ± 1. 45)%, H3K27me3: (66. 52 ± 15. 73)% vs (54. 51 ± 13. 60)%;P<0. 05]. (2) The expressions of pSTAT3, ETV5 and miR155 increased significantly in pa-tients with acute KD, while the expressions of negative regulators of pSTAT3 ( SOCS1 and SOCS3 ) were down-regulated. The expressions of pSTAT3, ETV5 and miR155 in KD-CAL+ group were higher than those in KD-CAL- group (P<0. 05), while the levels of SOCS1 and SOCS3 in KD-CAL+ group were lower than those in KD-CAL- group (P<0. 05). IVIG therapy restored the indexes mentioned above to some extent (P<0. 05). (3) Compared with the healthy subjects, the levels of inflammatory cytokines (IL-6, IL-23 and TNF-α) in plasma and the expressions of surface receptors (TLR4, IL-6Rα/gp130, IL-23R/IL-23Rβ1 and TNFR1) and its downstream adaptors (MyD88, TRIF, RIP1) in CD4+T cells were up-regulated in patients with acute KD (P<0. 05), but were down-regulated significantly after IVIG treatment (P<0. 05). Moreo-ver, all of the indexes mentioned above in KD-CAL+ group were found to be higher than those in KD-CAL-group (P<0. 05). Conclusion Aberrant patterns of IL-17-associated histone methylation might be related to the immune dysfunction in patients with KD.

Objective To study the best formulation and technology of quercetin-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate(PLGA-TPGS) nanoparticles(QPTN) with QT as model drug and PLGA-TPGS as polymer materials by orthogonal tests,and to investigate the in vitro stability of QPTN. Methods To ensure the best formula-tion and technology for preparing QPTN,single-factor test was established to determine the influence of the ratio of quercetin to PLGA-TPGS,the concentration of TPGS as emulsifiers,the ultrasonic power and ultrasonic time to the particle size,drug loading (DL) and entrapment efficiency(EE).According to single-factor test,the factor levels of nanoparticles were set to select the best prescription and technology of QPTN by orthogonal test.The stability of QPTN was examined using the effecting factor test,accel-eration test and long-term test. Results The best formulation and technology of QPTN was that the ratio of quercetin to PLGA-TPGS was 3:10 (W:W) with 0.05% TPGS as emulsifier,the mixed solution was sonicated for 6 min at 200 W.The average particle size,DL and EE of QPTN prepared under the conditions described above were (155.4 ± 2.7) nm,(21.6 ± 1.5)% and (93.7±2.9)% (n=6),respectively.In the in vitro stability test,QPTN showed a good stability at high temperature,high humidity and strong light condition. Conclusion The best formulation and preparation technology of QPTN was selected.QPTN got small particle size,high DL and EE,and good in vitro stability.