To prepare the mimetic exosomes and co-delivery proteins and nucleic acids, and achieve efficient and safe co-delivery of multi-component drugs, an optimized formulation was designed by modifying a polylactic acid-glycolic acid copolymer (PLGA) matrix with a cationic lipid excipient dioleyl trimethylammonium propane (DOTAP), and a PLGA/DOTAP nanoparticles packaged protein and nucleic acid was prepared by double emulsion method, and the outermost membrane structure prepared by reverse phase evaporation method and consists of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol and membrane proteins. The structure of the mimetic exosomes is formed by ultrasonic dispersion and extrusion, and analyzed its characteristics and nature of the transfer effect. The size of mimetic exosomes was about 156.13 nm, with negative charge (-18.23 ± 0.57 mV), and it could efficiently co-transfer protein and siRNA, and siRNA could effectively inhibit the expression of target gene Trim28. The mimetic exosomes simulate the structure of exosomes and achieve safe and efficient co-delivery of multi-component drugs.

Objective: To analyze the ratio of pulmonary valve ring to aortic valve ring (GA ratio), and to explore the application value of GA ratio in predicting the need of transannular patch in the radical operation of children with tetralogy of Fallot (TOF). Methods: A retrospective analysis was performed in 355 children (182 males and 173 females) with TOF and underwent radical operation in the Pediatric Cardiac Center of Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2016 to December 2017.They were divided into transannular patch group and non-transannular patch group.The values of pulmonary valve ring and aortic valve ring in two groups were collected, and the Z-score of pulmonary artery and GA ratio were calculated respectively for statistical analysis. Results: Among the 355 patients, 156 children (43.9%) required a transannular patch, and 199 patients (56.1%) did not receive transannular patch.The GA ratio and the Z-score of of pulmonary artery in the transannular patch group were lower than those in the non-transannular patch group [0.45±0.12 vs. 0.54±0.15, (-1.75±0.98) scores vs.(-0.86±1.39) scores], and the differences were statistically significant (t=5.29, 6.32, all P<0.01). Receiver operating characteristic curve analysis showed that in the case of the Z-score of pulmonary artery of -2 for the children received transannular patch, the area under the curve (AUC) was 0.702 (95%CI: 0.64-0.76), sensitivity was 69%, and specificity was 83%; in the case of the GA ratio of 0.58 for the children received transannular patch, the AUC was 0.712 (95%CI: 0.66-0.77), sensitivity was 70%, and specificity was 87%. Conclusions The GA ratio is a simple and effective predictor of transannular patch in the radical operation of TOF and can be applied in clinical practice.

PURPOSE: We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era. MATERIALS AND METHODS: From 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses. RESULTS: For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05). CONCLUSION: Our findings suggest IMRT +/– chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.
Adult ; Bone Marrow ; Comorbidity ; Dermatitis ; Drug Therapy ; Humans ; Methods ; Mucositis ; Multivariate Analysis ; Proportional Hazards Models ; Radiotherapy ; Radiotherapy, Intensity-Modulated* ; Temporal Lobe

Objective To study the effect of relatively closed environment dispensing mode on insoluble particles in pharmaceuticals.Methods The numbers of insoluble particles in conventional manual dispensing mode and relatively closed environment dispensing mode in lass Ⅰ and class Ⅲ environment were detected, effect of different dispensing modes on the number of insoluble particles in pharmaceuticals was compared.Results When adopting manual dispensing, the numbers of 1-10 μm insoluble particulates in different groups in class Ⅰ environment were less than those in class Ⅲ environment respectively, differences were all statistically significant (all P＜0.05). When adopting a new mode of dispensing in relatively closed environment, there was no significant difference in the numbers of 1-15 μm insoluble particulates in different groups between class Ⅰ and class Ⅲ environment respectively (all P＞0.05). The numbers of 1-20 μm and 1-15 μm insoluble particles in different groups were less than those in manual dispensing when the new mode of dispensing were adopted in class Ⅲ and class Ⅰenvironment respectively, differences were all statistically significant (all P＜0.05). The numbers of 1-15 μm insoluble particles in different groups in manual dispensing in class Ⅰ environment were more than those in class Ⅲ environment respectively, difference were all statistically significant (all P＜0.05).Conclusion The relatively closed environment dispensing mode can effectively reduce environmental particulates entering intravenous infusion system during dispensing process.

Objective: To observe the effect of STC-1 gene expression was inhibited on the apoptosis, IL-1β and TNF-α expression and JAK2/STAT3 signal in esophageal cancer cells. Methods: Compared with normal human esophageal squamous epithelial cells Het-1 A, STC-1 expression was detected in human esophageal squamous cell carcinoma KYSE170, Eca109, TE1 and TE10 cells by RTPCR and Western blot; the siRNA sequence that the synthesized STC-1 and the si NRA sequence without interference were transfected into Eca109 cells, which were labeled as STC-1-siRNA group and NC group, and the blank control group was set, cells were transfected for 48 h, the expression of STC-1 were detected by RT-PCR and Western blot. Eca109 cell viability and apoptosis rate were detected by CCK8 and flow cytometry. IL-1β and TNF-α expression were detected by RT-PCR; the expression of Ki67, p53, p-JAK2 and p-STAT3 protein were detected by Western blot. Results: Compared with Het-1 A cells, expression of STC-1 mRNA and protein in KYSE170, Eca109, TE1 and TE10 cells were increased significantly ( P＜0. 05); compared with the control group, STC-1 expression was decreased significantly in STC-1-siRNA group, cell viability was decreased significantly in STC-1-siRNA group, the apoptosis rate was increased significantly in STC-1-siRNA group; IL-1β, TNF-α, Ki67, p-JAK2 and p-STAT3 expression were decreased significantly in STC-1-siRNA group, p53 expression was increased significantly in STC-1-siRNA group ( P＜0. 05). Conclusion: STC-1 was highly expressed in esophageal cancer cells; inhibiting of STC-1 expression could significantly reduce the activity of cancer cells, and increase apoptosis rate, this effect may be related to the inhibition of JAK2/STAT3 signaling pathways and inflammatory factors as IL-1β and TNF-α.

Objective To explore the significance of the initial clinical symptoms and clinical manifestations of neuroblastoma(NB)to achive early identification of NB. Methods A retrospective study was performed on patients diagnosed with NB,who attended the Hematology Oncology Center,Beijing Childrenˊs Hospital from March 31st ,2007 to March 31st,2015. The clinical characteristics were compared between the children 〈1_year_old and≥1_year_old. The result was analyzed to compare the difference in clinical symptoms and tumor biologic characteristics of patients with different initial clinical symptoms between 2 groups. Results A total of 330 patients were included in the study,43 of them were younger than 1 year old,and their most common symptoms were cough and fever( each 17 cases,and accounted for 39. 5%,respectively);while the most common symptoms in patients≥1_year_old(287 cases)was fe_ver(177 cases,61. 7%),followed by lymphadenopathy(107 cases,37. 3%),bone pain(97 cases,33. 8%)and anemia (48 cases,16. 7%). The frequency of symptoms differed significantly between 2 groups(all P〈0. 05),such as fever (39. 5% vs. 61. 7%,χ2 ﹦6. 68),anemia(4. 7% vs. 16. 7%,χ2 ﹦6. 00),bone pain(0 vs. 33. 8%,χ2 ﹦18. 99),abdo_minal pain(0 vs. 25. 3%,χ2 ﹦10. 19),diarrhea(16. 3% vs. 3. 0%,χ2 ﹦12. 73),lymphadenopathy(7. 0% vs. 37. 3%, χ2 ﹦14. 12)and anorexia(9. 3% vs. 33. 4%,χ2 ﹦9. 21). Datients had fever,anemia,lymphadenopathy,cutaneous hemorrhagic spot or periorbital ecchymosis,bone pain,abdominal pain,exophthalmos,and anorexia early in the initial course of the disease,whose serum lactate dehydrogenase values were significantly increased(P〈0. 05). Datients suf_fered from fever,anemia,lymphadenopathy,bone pain,limbs dysfunctions,abdominal pain at the beginning of the disease,whose urine vanillymandelic acid values were higher than normal(P〈0. 05). Conclusions The study of sympto_mology suggests the most common symptoms in patients with NB 〈1_year_old are cough and fever,while those ≥1_year_old are fever,lymphadenopathy,bone pain,and anemia. Por patients with symptoms mentioned,carrying out the necessary NB_diagnose_related laboratory and imaging studies was statistically relevant to patientsˊ ages(〈1_year_old and≥1_year_old),which may contribute to earlier identification and diagnosis of NB.

Objective :To compare short-term and midterm therapeutic effect between sirolimus-eluting stent implan-tation (SES-PCI) and coronary artery bypass graft (CABG) in aged patients with coronary heart disease (CHD) and multi-vessel coronary disease (MVD).Methods : Aged MVD patients undergoing selective revascularization were en-rolled and divided into CABG group (n＝301) and SES-PCI group (n＝289).Major adverse cardio-and cerebrovas-cular events (MACCE) were followed up for 30d ,one ,two and five years .Logistic multi-factor regression was used to analyze independent risk factors for different therapeutic methods .Results : Compared with CABG group after 30d follow-up ,there was significant reduction in all-cause mortality (6-3% vs.2-8%) and significant rise in a sec-ond revascularization rate (RVR ,1-3% vs.8-3%) in SES-PCI group , P＜0-05 or ＜0-01 ;compared with CABG group during one ,two and five-year follow up ,there were significant reductions in all-cause mortality [one year :(11-6% vs.4-8%) ,five years :(23-3% vs.12-1%)] and incidence rate of cerebrovascular accidents [one year :(8-6% vs .3-5%) ,five years :(18-3% vs.6-9%)] ,and significant rise in incidence rate of non-fatal myocardial infarction [one year :(6-6% vs.11-8%) ,five years :(12-0% vs.24-9%)] and a second RVR [one year :(3-0%vs.16-3%) ,five years :(9-3% vs.24-6%)] in SES-PCI group , P＜0-05 or ＜0-01- Logistic multi-factor regres-sion analysis indicated that DM and EH were independent risk factors for SES-PCI (OR＝ 45-772 ,13-218 , P＝0-001 both) ,while peripheral vascular disease was independent protective factor for SES-PCI (OR＝ 0-007 , P＝0-001).Conclusion : Compared with CABG ,there are significant reductions in short-term and midterm all-cause mortality ,and significant rise in a second RVR in MVD patients undergoing PCI .

To compare short‐and mid‐term therapeutic effect on aged patients with multi‐vessel coronary disease between minimally invasive coronary artery bypass grafting (MIDCAB) and coronary artery bypass grafting (CABG).Methods : A total of 72 patients with multi‐vessel disease , who were suitable for MIDCAB from 2016 to 2018 , were regarded as MIDCAB group .Another 96 patients with multi‐vessel disease , who were not suitable for MIDCAB , were enrolled as CABG group (received selective on‐pump CABG).Clinical data and incidence of major adverse cardio‐ and cerebrovascular events (MACCE ) within two‐year follow‐up were compared between two groups.Results : Men percentage of MIDCAB group was significantly higher than that of CABG group (83. 3% vs. 67. 7%, P＝0.022) ; compared with CABG group , there were significant reductions in percentages of left anterior descending proximal lesions (61.5% vs.34.7%) and chronic total occlusion disease (57.3% vs.34. 7%) in MID‐CAB group ( P＜0. 01 both) , there were no significant difference in other indexes between two groups , P＞ 0. 05 all.All subjects were followed up for two years , follow‐up rate was 90. 5% .There were no significant difference in incidence rates of all‐cause death and MACCE between two groups , P＞0.05 all.Conclusion : There is no signifi‐cant difference in incidence rate of short‐and mid‐term events between CABG and MIDCAB in patients with multi‐vessel coronary disease .MIDCAB is recommended for proper patients in clinic .

Objective To investigate the role of Toll-like receptor 4 ( TLR4 ) and NOD-like receptor 3 (NLRP3)inflammasome in the liver injury of acute necrotizing pancreatitis (ANP) rat with obesity. Methods Twenty-four SD rats were randomly divided into normal group, ANP group, obesity group and obesity ANP group. The obesity rat model was established by continuously feeding high fat diet and the ANP model was induced by retrograde infusion of 5％ sodium taurocholate into the biliopancreatic duct. Rats were killed at 12 h after model establishment, and automatic biochemical immune analyzer were used for detecting serum AMY, LIP, ALT, AST, TG and TC. Pathological changes of pancreas and liver tissue samples were observed by miscroscopy and pathological score was recorded. The levels of MPO, CD68 , TLR4, NLRP3 and IL-1βin liver tissue were detected by immunofluorescence, and NF-κB and caspase-3 in liver tissue were detected by immunohistochemistry. Results The serum ALT and AST in obesity ANP group were significantly increased than those in ANP group (233. 00 ± 34. 44 U/L vs 102. 83 ± 8. 90 U/L,388. 00 ± 41. 60 U/L vs 282. 00 ± 21. 06 U/L);and liver pathologic score was also significantly higher than ANP group (6. 66 ± 1. 21 vs 3. 33 ± 1. 03);and CD68 + /TLR4 +, CD68 + /NLRP3 +, TLR4 + /NLRP3 +, MPO, NF-κB, IL-1β and caspase-3 level were all greatly higher in obesity ANP than those in ANP group, respectively (24. 16 ± 1. 47 vs 6. 66 ± 1. 21, 25. 00 ± 2. 60 vs 7. 00 ± 1. 41, 14. 16 ± 1. 47 vs 5. 50 ± 1. 04, 35. 33 ± 6. 88 vs 20. 83 ± 2. 48, 58. 80 ± 6. 75 vs 37. 63 ± 2. 96, 50. 00 ± 2. 36 vs 35. 00 ± 2. 82, 66. 00 ± 4. 04 vs 55. 00 ± 2. 60); and all the differences were statistically significant (all P<0. 05). Conclusions Liver injury was more severe in ANP rats with obesity, which may be related to the fact that obesity may enhance the activation of TLR4/NLRP3 signal pathway and result in the release of more inflammatory factors.

Panic disorder (PD) is an acute paroxysmal anxiety disorder with poorly understood pathophysiology. The dorsal periaqueductal gray (dPAG) is involved in the genesis of PD. However, the downstream neurofunctional changes of the dPAG during panic attacks have yet to be evaluated in vivo. In this study, optogenetic stimulation to the dPAG was performed to induce panic-like behaviors, and in vivo positron emission tomography (PET) imaging with F-flurodeoxyglucose (F-FDG) was conducted to evaluate neurofunctional changes before and after the optogenetic stimulation. Compared with the baseline, post-optogenetic stimulation PET imaging demonstrated that the glucose metabolism significantly increased (P < 0.001) in dPAG, the cuneiform nucleus, the cerebellar lobule, the cingulate cortex, the alveus of the hippocampus, the primary visual cortex, the septohypothalamic nucleus, and the retrosplenial granular cortex but significantly decreased (P < 0.001) in the basal ganglia, the frontal cortex, the forceps minor corpus callosum, the primary somatosensory cortex, the primary motor cortex, the secondary visual cortex, and the dorsal lateral geniculate nucleus. Taken together, these data indicated that in vivo PET imaging can successfully detect downstream neurofunctional changes involved in the panic attacks after optogenetic stimulation to the dPAG.