AIM: Using optical coherence tomography angiography (OCTA) to observe the changes and clinical significance of macular blood flow density in patients with diabetic retinopathy (DR).METHODS: Totally 47 eyes (28 patients) with diabetic retinopathy (DR) were enrolled in the DR group.According to the international clinical grading criteria of diabetic retinopathy, 30 eyes (19 patients) with non-proliferative diabetic retinopathy were classified as the NPDR group, and 17 eyes (11 patients) with proliferative diabetic retinopathy were classified as PDR group.A total of 46 (27 subjects) healthy eyes with matched age were enrolled in the control group.All the subjects underwent the 3mm×3mm scanning of macular retina by optical coherence tomography angiography (OCTA), obtaining 4 levels of macular blood flow density map.The macular blood flow density at 3 levels, including superficial retinal layer, deep retinal layer and choroidal capillaries layer, were measured.RESULTS: The macular blood flow density of superfical retinal layer, deep retinal layer and choroidal capillaries layer in DR group were 0.4963±0.0840, 0.4798±0.0801 and 0.5290±0.0528, respectively.Among them, the blood flow density of each layer were 0.5064±0.0843,0.4983±0.0766,0.5345±0.0529, respectively, for the NPDR group, and were 0.4786±0.0830, 0.4473±0.0778,0.5192±0.0526, respectively, for the PDR group.For the control group, the density of each layers were 0.5919±0.0704, 0.6301±0.0527, 0.5691±0.0169, respectively.The macular blood flow density was significantly different in the superficial retinal layer, deep retinal layer and choroidal capillary layer between the control group and the NPDR group, as well as the PDR group and the DR group (total P<0.001).Statistically significant difference was found between the NPDR group and the PDR group in the deep retina layer (P=0.029), but not in the superficial retina layer and choroid capillary layer (P=0.236, 0.268).CONCLUSION: Compared with the control group, the macular blood flow density of superficial retinal layer, deep retinal layer and choroidal capillary layer in the patients with diabetic retinopathy decreased significantly.It indicated that the macular ischemia existed in both retina and choroid.By quantitatively measurement of the macular blood flow, OCTA may be used for monitoring the progression of diabetes, and early detection of diabetic retinopathy.

Background Anti-VEGF drugs are generally applied in the treatment of ocular neovascular diseases.However,the therapy effect is unsatisfactory in some patients.Studing the effect of hypoxia-inducible factor-1 (HIF-1),a upstream regulatory gene of VEGF,and its limiting enzyme prolyl-4-hydroxylase domain proteins (PHDs) is of important clinical significance.Objective This study was to investigate the negtive regulation of exogeneous PHDs on HIF-1 pathway in human RPE cells.Methods pFLAG-PHD1,pFLAG-PHD2 and pFLAG-PHD3 plasmids were constructed by extracting RNA from Hela cell line and coloning PHD1,PHD2 and PHD3 using reverse transcription PCR with restriction enzyme.The plasmids were identified by gene sequencing.ARPE-19 cells were cultured at 21％ O2 (normoxia group),1％ O2 (hypoxia group),or in hypoxia-mimicking agents (CoCl2,anoxia group),respectively,and then were transfected with plasmids encoding FLAG-tagged PHD1,PHD2,PHD3 and pFLAGCMV2 transfected cells served as blank control.The expressional intensities of PHD1,PHD2 and PHD3 in the cells were detected and compared among different groups by using Western blot assay.The transcriptional activity of HIF-1 in the cells was evaluated with dual luciierase reporter assay.Results Western blot assay showed that PHD1,PHD2 and PHD3 all were expressed in ARPE-19 cells in the normoxia group,hypoxia group and anoxia group.The expression was strong in PHD2 protein and was weak in PHD3 protein,a statistically significant difference was found between PHD2 protein expression and PHD1 or PHD3 expressions (all at P＜0.05).Endogenous HIF-1 activity was elevated in pFLAG-CMX transfected cells in the hypoxia group and anoxia group than that in the normoxia group.Compared with pFLAG-CMX transfected cells,no obvious change was seen in the endogenous HIF-1 activity in the normoxia group,however,HIF-1 activity was declined in the hypoxia group and anoxia group after pFLAG-PHD1,pFLAG-PHD2 or pFLAG-PHD3 transfection.Under the same oxygen environment,HIF-1 activity was lower in the pFLAG-PHD2 transfected cells than that in the pFLAG-PHD1 or pFLAG-PHD3 transfected cells (both at P＜0.05).Conclusions PHDs play a negative regulation to HIF-1 activating pathway in human RPE cells,especially in hypoxia and anoxia cells.Among PHDs proteins,PHD2 presents the strongest inhibition on HIF-1 activating pathway.

Objective:To preliminarily explore the synthesis of a quercetin derivative 3′,4′,5,7-four-(O-methoxy carbonyl meth-yl) quercetin and its pharmacological activities. Methods:Quercetin as the reactant and N,N-dimethyl-formamide ( DMF) as the sol-vent, the target product 3′,4′,5,7-four-(O-methoxy carbonyl methyl) quercetin was obtained by the slow addition of methyl chloroace-tate in the presence of anhydrous K2 CO3 to introduce ether bond at 3′,4′,5,7- bit. The structure was characterized by LC-MS, 1 H-NMR and element analysis. The nanoemulsion of the product was prepared using a film dispersion method, and with intraperitoneal in-jection, the effect on pituitrin-induced myocardial ischemia cardiovascular system in rats was observed. Results:3′,4′,5,7-Four-(O-methoxy carbonyl methyl) quercetin was successfully synthesized, and could be metastasized to a demethylation product containing dis-tal free carboxyl with increased polarity proved by metabolic tests in vitro. The results of electrocardiogram and animal experiments showed that the compound had improving effects on pituitrin-induced myocardial ischemia in rats. Conclusion: The nanoemulsion of 3′,4′,5,7-four-(O-methoxy carbonyl methyl) quercetin with intraperitoneal injection shows significant antagonism against pituitrin-in-duced myocardial ischemia in rats.

OBJECTIVE:To detect the expressions of five gastric cancer cell metastasis associated genes induced by arsenic trioxide METHODS:The expressions of CD44,P53,nm23,H-ras,PCNA induced by arsenic trioxide were examined by immunohistochemistry method RESULTS:Arsenic trioxide induced the decrease of the expressions of CD44,P53,PCNA in gastric cancer cells;the expressions of nm23 and H-ras were not changed by As2 O 3 CONCLUSION:It is tentatively proved that the antineoplastic action of As2 O 3 may be related to the down-regulation of CD44,P53 and PCNA

OBJECTIVETo explore potency material bases of Xuebijing (XBJ) formula, and to analyze its effects at the molecular network level.

METHODSTotally 16 sepsis-related targets were selected and classified into three categories such as inflammation, immune, and coagulation referring to biological roles. Then molecular database of chemical compositions in XBJ formula were constructed to explore mutual actions with inflammation, immune, and coagulation targets.

RESULTSDanshen root and safflower, with more effector molecules with immune and coagulation targets, have extensive anticoagulation and anti-inflammation effects. The former 10 molecules with better mutual actions with sepsis targets were sequenced as tryptophane, danshensu, gallic acid, salvianolic acid D, protocatechuic acid, salvianolic acid A, danshensu C, vanillic acid, rosmarinic acid, phenylalanine. There existed two phenomena in XBJ formula as follows. One component had stronger actions with multi-targets, for example, danshensu had actions with 13 targets. Meanwhile, different components acted on the same target protein, for example, 8 molecules acted with MD-2.

CONCLUSIONXBJ formula had certain potential synergistic effects with sepsis targets, which could provide certain referential roles for findina new type anti-septic drugs.

Caffeic Acids ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Gallic Acid ; Hydroxybenzoates ; Inflammation ; Lactates ; Sepsis ; drug therapy

Objective To explore the feasibility of imaging and treatment of cervical cancer xenograft model using 131I mediated by hNIS gene transfection. Methods The cervical cancer xenograft models were established with Hela-NIS( +) cells and Hela cells, respectively. Five Hela-NIS( +) xenograft models and five Hela xenograft models were dynamically imaged at 0.5, 1, 2, 4, 8, 16 and 20 h postinjection of 131I(7.4 MBq). Five Hela-NIS( +) xenograft models were imaged at 0. 5,1,2,4,8,16, 20 and 25 h postinjection of 99TcmO4-(11.1 MBq). Twenty Hela-NIS( +) cervical cancer xenograft models were randomly divided into four groups: Three 131I treating groups and one control group. The therapeutic effects of 131I at threelevels (74,111,148 MBq) were investigated following intraperitoneal injection. Results Hela-NIS( +)human cervical cancer xenografts were established successfully in nude mice. The Hela-NIS( +) xenografts significantly accumulated radioactivity after intraperitoneal injection of 131I, and the radioactivity was persistently present until 20 h postinjection, but Hela xenografts had no radioactive accumulation. The T/B value of the Hela-NIS( +) xenografts reached 17.34 at 8 h postinjection. The imaging with 99TcmO4- showed that the radioactivity was persistently present in Hela-NIS( +) xenografts for almost 25 h. The Hela-NIS( +)xenografts shrinked after 131I treatment. The inhibition ratios of tumor growth in 111 MBq and 148 MBq groups were both significantly higher than that of 74 MBq group (t: 2.74-5.75, P ＜0.05). Conclusions Hela-NIS( +) cervical cancer xenografts in nude mice could persistently accumulate 131I and 99TcmO4- and could be treated successfully with 131 I. 131 I treatment mediated by hNIS gene transfection could be a promising cancer treatment method.

Background Ginkgolide B (GB) has been proved to have neuroprotective and anti-apoptotic effects and can effectively inhibit apoptosis of retinal photoreceptor cells.But the high hydrophobic feature and low bioavailability of GB limit its clinical application.Self microemulsifying drug delivery system (SMEDDS) can effectively improve the infusibility drug dissolution and bioavailability in the retina.Objective This study was to investigate the pharmacokinetics and drug-time change of GB-loaded SMEDDS in retina.Methods Eighty SD rats were randomized into 2 groups,2.5％ GB(40 mg/kg) of SMEDDS or GB suspension(0.1％ DMSO dissolve) were gastrically given respectively in two groups.The rats were sacrificed and retinas were isolated 15,30,45 minutes and 1 hour,2,4,8,12 hours to prepare the retinal suspension.The content of GB in retina was assayed with high performance liquid chromatography-electrospray ionization-(1) (1)ss spectrum (HPLC-ESI-MS) and contrasted with standard curve.Practical drug dynamics program 3p87 was used to detect the pharmacokinetics parameters.The maximal content(Cmax,mg/g),time to peak (Tmax,h),clearance ratio (Ke/h),high-life period (t1/2) and area under the concentration-time curve(AUC0-∞,mg/(g · h)) of GB in various time points in retina after a single oral dose were calculated and compared between two groups.Results The standard curve was obtained over the concentration range of 1-32 mg/L with a linear regression equation,Y =0.0732X + 0.056 (r =0.992).A similar content-time curve was seen between GB suspension group and GB-SMEDDS group.The GB content was higher in GB-SMEDDS group than that in GB suspension group from 30 minutes through 12 hours after administration of drugs.The Cmax of GB-SMEDDS group and GB suspension group were(15.83±1.84) mg/g and(2.65±0.10) mg/g,the AUC0-∞ were(15.30±0.11)mg/(g· h)and(6.42±0.19)mg/(g · h).Conclusions HPLC-ESI-MS is proved to be a rapid,accurate,sensitive and suitable method for pharmocokinetic study of GB.SMEDDS can raise the concent of GB in retina,and it probably improve the bioavailability of GB.

Objective To investigate the pathogen culturing of the catheter related infection(CRI),cathe-ter related bloodstram infection(CRB)and risk factors after central venous catheter(CVC)of cardiovascular surgery in order to provide the beneficial reference.Methods From Jan 2005 to Dec 2005,a total of 300 cases central ve-nous cathers were determined,and the cusp of the catheters was determined by bacteria cultivation,and blood bacte-ria cultivation.Results The infection happened in 35 of 300 patients with inserted central venous catheter.The cusps of CRI rate was 11.7%.CRB rate was 1.7%.54.3%pathogens were gram-positive cocci,34.3% were gram-negative bacilli,11.4% were fungi.The most common strain were Staphylococcus epidermis,Staphylococcus aureus,Klebsiella pneumoniae,Pseudomonas aeruginose,and Candiadia albicans.The infection rate increased obviously when the dwelling time>6 d.Conclusion CRI and CRB are the most severe complication of CVC,and it is important to cut down the death with the early diagnosis and applying antibiotics rationally.

Objective To investigate the clinical value of amplitude integrated electroencephalogram on early diagnosis and prognosis evaluation of brain injury caused by neonatal asphyxia.Methods A total of 34 full-term asphyxiated neonates(asphyxia group)hospitalized in NICU of our hospital from January 2015 to September 2015 were selected;meanwhile,34 full-term healthy infants(control group)of the same term were selected.All cases were monitored for the activities of aEEG background,sleep-awakening cycle(SWC)and epileptic activity(SA)within 6 hours after birth.Meanwhile,the relationships between various indexes and asphyxia degree and brain injury were analyzed.Results The electroencephalogram of the asphyxia group was 52.9％and the rate of SWC was 58.8％,which were lower than those of the control group,and the difference had statistic significance(P<0.05).Meanwhile,neonates with epileptic activity in asphyxia group accounted for 11.8％,which was higher than that of control group significantly(P<0.05).Conclusion The AEEG changes of neonates at early period after birth are closely related to perinatal asphyxia and brain injury after asphyxia.The application of amplitude integrated electroencephalogram has an important significance on early diagnosis of neonatal asphyxia.

Objective To evaluate the immune effects of virus-like particles ( VLPs) of VP1 pro-teins derived from norovirus GⅠ. 1 and GⅡ. 4 genotypes expressed in Hansenula polymorpha expression sys-tem. Methods SDS-PAGE and Western blot assay were performed to detect the purity of GⅠ. 1 and GⅡ. 4 VP1 proteins after purification. Morphologies of the recombinant VLPs were observed under transmission electron microscopy ( TEM) . Sizes and distributions of the VLPs were analyzed by dynamic light scattering analyzer. BT50(50% of blocking titer) was detected by HBGA (histo-blood group antigen) blocking assay in BALB/c mice immunized with different regimens. Results SDS-PAGE analysis of the purified recombinant GⅠ. 1 and GⅡ. 4 VP1 proteins showed that their purity were greater than 90%. Western blot assay con-firmed the specific bands of VLPs. TEM images showed that the sizes of purified GⅠ. 1 and GⅡ. 4 VP1 VLPs were at a mean diameter of 30-50 nm with clear border and high homogeneity, which was similar to that of wild virus. BT50 significantly increased in the groups, in which Al( OH) 3 was used as adjuvant. Con-clusion Animal studies have shown that administration of GⅠ. 1 and GⅡ. 4 VP1 VLPs in the presence of Al( OH) 3 induces detectable HBGA-blocking antibody, indicating that GⅠ. 1 and GⅡ. 4 VP1 VLPs are promising candidates for norovirus vaccine.