Fundus neovascularization disease is a series of clinicopathological changes caused by pathological vascular growth of choroid and retina.It is a kind of fundus disease that seriously affects vision.At present, it is believed that the main cause of the disease is the imbalance between the promoters and inhibitors of angiogenesis.Currently widely used drugs against vascular endothelial growth factor (VEGF) are still ineffective in many patients with fundus neovascularization.Adiponectin (APN) is an endogenous bioactive protein secreted by adipocytes, which has the functions of increasing insulin sensitivity, regulating sugar and lipid metabolism, anti-inflammatory, and inhibiting neovascularization.In recent years, it has been found that APN and its receptors play an important role in fundus neovascularization diseases.Many studies have demonstrated the clinical predictive value of APN gene polymorphism in fundus neovascularization diseases. In vivo and in vitro models have verified the important proportion of APN in the pathological mechanism of chronic inflammation and neovascularization.The mechanism may be that APN inhibits VEGF-stimulated endothelial cell migration, and maintains normal vascular endothelial cell function .At this point we do not know whether APN is pro or anti angiogenic molecule in eye.Understanding the role of APN and its receptors in fundus neovascularization diseases is expected to provide potential therapeutic targets and new ideas for the prevention and treatment of fundus neovascularization diseases.This article reviews the role of APN and its receptor in fundus retinal neovascularization disease.

Objective:To investigate the genetic safety of allogeneic bone marrow mesenchymal stem cells (BMSCs) transplantation in traumatic brain injury (TBI).Methods:(1) In vivo experiment: BMSCs from male SD rats were isolated and cultured. Moderate TBI models were prepared by implanting and fixing micro-drug injection cannula into the left ventricle of 12 female SD rats, and 3 d after that, striking the right cerebral cortex of the rats with pneumatic precision percussion device was performed. Four h, and 3, 6, 9, and 12 d after modeling, TBI rats were given a single/multiple BMSCs infusion (2.5×10 5/time, total volume 10 μL) by cannula; 48 and 72 h, and 10 and 14 d after modeling, brain tissues of TBI rats (3 at each time point) were prepared into paraffin specimens. Immunofluorescent staining was used to detect the microglia activation, and RNAscope ? technology was used to detect the co-localization of astrocytes, neurons, microglia and transplanted BMSCs to observe whether the allogeneic BMSCs were integrated with the host brain cells after transplantation into TBI host. (2) In vitro experiment: the frozen and revived microglial cell line BV2 was transfected with green fluorescent protein (GFP)-positive lentiviral particles, and then, BMSCs prelabeled with pHrodo RED probe and BV2 cells pretreated with lipopolysaccharide were co-cultured in a certain ratio (BV2:BMSCs=1:1, 1:2, 2:1); after 36 and 72 h of co-culture, the phagocytosis between the 2 kinds of cells was observed under confocal fluorescence inverted microscope to observe the specific action forms of microglia on BMSCs. Results:(1) In vivo experiment: 48 and 72 h, and 10 and 14 d after modeling, no colocalization of transplanted BMSCs with astrocytes or neurons was found in paraffin sections of brain tissue in TBI rats; however, 10 and 14 d after modeling, microglia in TBI rats were obviously activated and migrated to the left lateral ventricle and choroid plexus, and co-localization of microglia with transplanted BMSCs was observed. (2) In vitro experiment: phagocytosis occurred after co-culture of BV2 cells at different proportions with BMSCs for 36 and 72 h. Conclusion:After transplantation, allogeneic BMSCs do not integrate with astrocytes or neurons of the TBI host, but they could be phagocytosed by microglia, indicating that allogeneic BMSCs transplantation for TBI is genetically safe.

Humans ; Nitric Oxide ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms ; Lung ; Nitric Oxide Synthase ; Macrophages, Alveolar ; Pulmonary Alveoli

Objective:To investigate the current situation of telephone cardiopulmonary resuscitation (T-CPR) in China, and analyze the reasons for the low implementation rate of T-CPR.Methods:This was a multicenter cross-sectional survey. Twenty cities were selected from six geographical regions of China by convenient sampling method. Anonymous online electronic questionnaires were sent to emergency medical service staffs in each city. All respondents were divided into the routine T-CPR group and control group. Student's t test and Chi-square test were used to analyze the difference between groups. Multivariate logistic regression was used to analyze the influencing factors of T-CPR. Results:⑴A total of 1 191 questionnaires were collected. 80.94% of respondents knew T-CPR. Nine hundred and sixty respondents, who knew T-CPR and completed the questionnaires, were included in the study, and were divided into the routine T-CPR group ( n=401) and control group ( n=559). Nine hundred and thirty-nine (97.81%) responders believed that T-CPR should be implemented for cardiac arrest patients that could be confirmed by telephone.⑵Four hundred and one (41.77%) responders routinely implemented T-CPR. Among them, 237 (24.68%) responders always did and 164 (17.08%) responders often did. ⑶Multivariate logistic regression analysis showed that male ( OR=1.787, 95% CI: 1.235-2.587, P=0.002), age ( OR=1.025, 95% CI: 1.004-1.047, P=0.020), clinical medicine background ( OR=2.926, 95% CI: 1.387-6.171, P =0.005), dispatcher ( OR=5.305, 95% CI: 3.463-8.126, P<0.01), using medical priority dispatch system (MPDS) system ( OR=1.941, 95% CI: 1.418-2.656, P<0.01), and T-CPR policy or procedure ( OR=3.879, 95% CI: 2.652-5.674, P<0.01) were favorable factors for T-CPR. ⑷The top three reasons for implementing T-CPR in the routine T-CPR group were that they had received T-CPR training (67.08%), believed that T-CPR could improve survival rate (63.59%), and had standard T-CPR process (63.09%). The top three reasons for not implementing T-CPR in the control group were that worrying about bystander compliance (42.04%), worrying about the quality of bystander cardiopulmonary resuscitation (CPR) (38.28%), and worrying about medical dispute (36.14%). Conclusions:The awareness and implementation of T-CPR among emergency medical service staffs need to be improved. The implementation of T-CPR depend on telephone dispatchers with clinical medicine background, clear T-CPR policy, standardized operation procedure, and professional assistant tools. To improve the public's awareness of cardiac arrest and cardiopulmonary resuscitation, and to improve the supporting legal system are also conducive to the implementation of T-CPR.

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Objective:To investigate the reproducibility of inflow-based vascular-space-occupancy (iVASO)-MRI in quantifying skeletal muscle perfusion and its potential clinical value in patients with dermatomyositis (DM).Methods:Totally 15 consecutive patients with DM and 15 healthy volunteers were enrolled in this prospective study from December 2018 to April 2019 at Nanfang Hospital, Southern Medical University. All subjects underwent T 1WI, short-tau inversion recovery (STIR) T 2WI, and iVASO-MRI of thigh on a 3.0 T MR scanner. According to findings on T 1WI and STIR T 2WI, the muscles were divided into normal, unaffected, edematous and atrophic or fat-infiltrated groups. Maximum arteriolar muscular blood volume (MBVa_max) and mean MBVa (MBVa_mean) of these 4 groups of muscles were obtained by 2 radiologists independently. In order to evaluate the reproducibility of iVASO, the repeated scan was performed 3 days later in 17 subjects (12 healthy volunteers and 5 DM patients), and the MBVa values were measured to calculate the intraclass correlation coefficients (ICC). The MBVa_max and MBVa_mean among the 4 groups were compared by using Kruskal-Wallis H test and the differences of each 2 groups was compare by using Mann-Whitney U test. Results:The ICC between the 2 observers was 0.95 and 0.96 for MBVa_max and MBVa_mean, respectively. The ICC between repeated tests was 0.87 and 0.89 for MBVa_max and MBVa_mean, respectively.There was significant difference among normal muscles, unaffected muscles, edematous muscles and atrophic or fat-infiltrated muscles ( P<0.001). Post hoc comparisons of MBVa_max and MBVa_mean showed that compared to normal muscles, unaffected muscles, edematous muscles and atrophic or fat-infiltrated muscles had a significant decrease of MBVa ( P<0.05). Unaffected muscles and edematous muscles showed no significant difference in terms of MBVa_max and MBVa_mean (both P=0.99), which were significantly higher than those of atrophic or fat-infiltrated muscles ( P<0.05). Conclusions:iVASO-MRIcan reliably quantify the MBVa of thigh muscular arteriolar, and it is potentially valuable in the diagnosis of DM.

Objective: To identify the differentially expressed miRNAs in the exosomes secreted from γ-ray irradiated cells and provide new clues in disclosing the mechanisms of radiation-induced bystander effects. Methods: The human bronchial epithelial cells (BEP2D) were irradiated with ⁶⁰Co γ-rays, and the exosomes were collected by ultracentrifugation from the culture medium of 2 Gy-irradiated cells and non-irradiated control. The exosomes were identified by an electron microscopy. The miRNA microarray technique was used to analyze the miRNA expression profiles in the exosomes. qRT-PCR was used to verify the miRNAs expression. The functional pathways of miRNAs targeting genes were predicted by informatic analysis using the databases of TargetScan, miRanda, GO and KEGG. Results: Sixteen miRNA with significantly increased expression (P<0.05) were identified in the exosomes of BEP2D cells at 4 h post-2 Gy irradiation as compared with the non-irradiated control cells, among which miR-100-5p, miR-1246, miR-29b-3p, and miR-7-5p were further confirmed to be unregulated by qRT-PCR assay (P<0.05). Meanwhile, the expression changes of above-mentioned four miRNAs were also investigated in the irradiated cells. The data indicated the expression was significantly increased at 2 h post-2 Gy irradiation for the miR-100-5p, miR-1246, miR-29b-3p in addition to miR-7-5p. However, all these four miRNAs were downregulated in the cells at 4 h post-irradiation and then gradually recovered. Bioinformatics analysis showed that the targeted genes of these differentially expressed miRNAs might participate in the biological processes and signal pathways of cell adhesion, mTOR signal pathway, chromatin modification, HR and NHEJ pathways of DNA repair and so on. Conclusions Radiation-inducible miRNAs have been identified in the exosomes from the irradiated BEP2D cells. The target genes of these miRNAs play roles in a series of important biological processes and functional pathways, which provides new clues in elucidating the mechanisms of radiation-induced bystander effects.

OBJECTIVETo assess the association of programmed cell death 1 (PDCD1) gene polymorphisms with the susceptibility and/or progression of colorectal cancer.

METHODSA hospital-based case-control study was carried out, which recruited 426 colorectal cancer patients and 500 healthy individuals. Five single nucleotide polymorphisms, namely rs36084323, rs11568821, rs2227981, rs2227982 and rs10204525, were selected for the study and genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.

RESULTSThe G allele of rs36084323 under a dominant model was associated with increased risk of advanced TNM staging of colorectal cancer progression (OR=1.59, 95%CI=1.02-2.48). Haplotypes G-G-C-T-A and A-G-C-C-G of the rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525 were negatively associated with the occurrence of colorectal cancer.

CONCLUSIONThe G allele of rs36084323 is associated with increased risk of advanced TNM staging of colorectal cancer. Conversely, the incidence of colorectal cancer is negatively associated with the haplotypes G-G-C-T-A and A-G-C-C-G of rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525.

Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; ethnology ; Colorectal Neoplasms ; genetics ; pathology ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Neoplasm Staging ; Polymorphism, Single Nucleotide ; Programmed Cell Death 1 Receptor ; genetics

OBJECTIVE:To establish a method for the determination of brucine concentration in plasma of rats,and to compare the pharmacokinetic differences between brucine and its nanostructure lipid carrier (NLC) in rats. METHODS:Sixteen male SD rats were randomly divided into brucine NLC solution group and brucine solution group(using normal saline as solvent, and containing brucine 1.28 mg/mL),with 8 rats in each group. They were given relevant solution 10 mg/kg via tail vein. Blood sample 0.5 mL was collected from fundus venous plexus capillary before medication and 15,20,30,40,45,60,90,120,150, 180,210,240,480 min after medication. HPLC method was adopted. The determination was performed on Dikma C18column with mobile phase consisted of methanol-water containing acetic acid and triethylamine(30∶70,V/V)at the flow rate of 1 mL/min. The detection wavelength was set at 265 nm,and column temperature was 30 ℃. Sample size was 10 μ L. Pharmacokinetic parameters of rats in 2 groups were calculated by using DAS 2.0 software,and the difference of them were compared by F test. RESULTS:The linear range of brucine plasma concentration were 1.03-66.00 μg/mL(R2＝0.999 6);the limit of quantitation was 1.03 μg/mL,and lowest detection limit was 0.515 μg/mL. RSDs of intra-day and inter-day were lower than 5%;method recoveries were 84.90%-100.88%, extraction recoveries were 80.60%-91.98%(all RSDs were lower than 10%). Average plasma concentration-time curve of single administration of brucine NLC solution and brucine solution were all in line with two-compartment model after medication via tail vein. The pharmacokinetic parameters included t1/2αwere(0.24±0.11)and(0.06± 0.03)h;t1/2 βwere (2.90 ± 0.22) and (0.57 ± 0.32)h;AUC0-twere (88.00 ± 6.98) and (28.50 ± 5.87)μg·h/mL;AUC0-∞were (109.96±7.99)and(45.06±6.66)μg·h/mL. Compared with brucine solution group,t1/2 α,t1/2 β,AUC0-tand AUC0- ∞of brucine NLC solution group were increased significantly;while CL, k10and k12were decreased significantly, with statistical significance (P＜0.05 or P＜0.01). There was no statistical significance in k21between 2 groups (P＞0.05). CONCLUSIONS: Established HPLC method is simple, specific,sensitive,precise and highly recoverable. It can be used for the determination of plasma concentration and phamacokinetic study of brucine in rats. After brucine NLC is prepared,the pharmacokinetic parameters of brucine change significantly;retention time of brucine is significantly prolonged and the clearance rate decreases significantly.