Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Objective: To investigate the incidence and prognosis of tricuspid regurgitation after transcatheter closure of perimembranous ventricular septal defects in pediatric patients as well as the risk factors of regurgitation occurrence or aggravation. Methods: Clinical data of 1 108 patients who underwent percutaneous closure in Shanghai Children′s Medical Center, School of Medicine, Shanghai Jiaotong University from January 2011 to January 2017 was analyzed retrospectively, and the prognosis and risk factors of postoperative tricuspid regurgitation and aggravation were also analyzed. Results: Mild tricuspid regurgitation occurred in 24 cases after surgery with the incidence of 2.1%.Among 5 cases with mild or above preoperative tricuspid regurgitation, the regurgitation was alleviated after surgery in 4 cases.No severe tricuspid regurgitation requiring surgical intervention occurred in any patient during follow-up.Univariate analysis showed that intervention time (P<0.05) and residual shunt (P<0.05) were risk factors for mild or above tricuspid regurgitation after intervention.Binary regression analysis indicated that the size of the occluder (mm) (OR=1.48, 95%CI: 1.13-1.90) and residual shunt (OR=6.53, 95%CI: 1.69-25.30) were risk factors for tricuspid regurgitation after intervention (all P<0.05). Conclusions There is a certain incidence of tricuspid regurgitation after transcatheter closure of perimembranous ventricular septal defects, but most tricuspid regurgitation do not need surgical intervention.The intervention time, size of occluder and residual shunt are risk factors of intraoperatively or postoperatively tricuspid regurgitation.

Objective To explore the effects of graphene oxide (GO)-polyethylene glycol (PEG)-folic acid (FA)-pyrenemethylamine hydrochloride (PyNH2)-mediated RNA interference (RNAi) of hypoxia-inducible factor-1α (HIF-1α) on the biological behaviors of human pancreatic cancer Patu8988 cells.Methods GO-PEG-FA-PyNH2 and RNAi targeting HIF-1α gene (GO-PEG-FA-PyNH2-HIF-1α-RNAi)was constructed.The expressions of HIF-1α and glucose transporter 1 (Glut-l) in Patu8988 cells were determined after knockdown of HIF-1α by RNAi.The invasive ability,the proliferation and the cell cycle of Patu8988 cells were investigated.The effect of HIF-1α knockdown on the uptake of 18F-fluorodeoxyglucose (FDG) in Patu8988 cells was also detected.Comparison of data was conducted by one-way analysis of variance and least significant difference t test.Results The GO-PEG-FA-PyNH2 was successfully constructed,and no cytotoxicity was found.Under the hypoxia or normoxia state,the mRNA and protein levels of HIF-1α and mRNA level of Glut-1 in cells transfected with GO-PEG-FA-PyNH2-HIF-1α-RNAi (study group) were lower than those in cells transfected with GO-PEG-FA-PyNH2 (negative group) and cells transfected with Opti-minimal essential medium (Opti-MEM,control group;F=30.25-32.58,t=3.66-5.81,all P＜0.05);the numbers of migrated cells in the study group were much lower than those in the negative group and the control group (F=38.63 and 41.35,t=20.51-35.25,all P＜0.01);the cell proliferation in the study group was significantly lower than that in the negative group and the control group (F=35.19 and 38.11,t =15.11-22.19,all P＜0.05).The proportions of G0/G1 cells in the study group were higher than those in the negative group and the control group (F=34.60 and 34.83,t=11.55-34.56,all P＜0.05);the 18 F-FDG uptake in the study group was lower than that in the negative group and control group (F=29.85 and 31.69,t =3.35-4.35,all P＜0.05).Conclusion GO-PEG-FA-PyNH2-mediated HIF-1α RNAi inhibits the expression of HIF-1α in pancreatic cancer cells,leading to changes in related biological behaviors.

Objective To evaluate the predictive value of 18F-fluorodeoxyglucose (FDG) PET/CT before or after autologous hematopoietic stem cell transplantation (Auto-HSCT) in patients with non-Hodgkin's lymphoma (NHL).Methods Fifty-eight NHL patients who underwent PET/CT scan before or after Auto-HSCT were retrospectively analyzed.Between June 2007 and May 2016,40 patients (32 males,8 females;median age 39 years) underwent 18F-FDG PET/CT pre-transplantation,and 34 patients (23 males,11 females;median age 34 years) underwent 18F-FDG PET/CT post-transplantation.There were 16 patients underwent both pre-and post-transplantation imaging.PET/CT results were categorized as positive or negative according to the standard response criteria.The predictive value of PET/CT was evaluated with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis and logrank test.Three-year PFS and OS of different groups were compared with Fisher exact test.Results (1) 18 F-FDG PET/CT before Auto-HSCT:PFS of patients in PET/CT negative group (n =27) and positive group (n=13) were significantly different (x2=4.187,P＜0.05),3-year PFS was 63.6％(14/22) vs 1/7 (P=0.031).However,OS of the 2 groups were not significantly different (x2=1.777,P＞0.05).(2)18F-FDG PET/CT after Auto-HSCT:PFS and OS of patients in PET/CT negative group (n=18) and positive group (n =16) were significantly different (x2 values:15.430,7.726,both P＜0.01).The 3-year PFS and OS of the 2 groups were 8/10 vs 2/12(P=0.005) and 8/10 vs 4/12 (P=0.038),respectively.Conclusion 18F-FDG PET/CT before or after Auto-HSCT could provide prognostic information for NHL patients.

Objective To compare the clinical efficacy and safety of carbon dioxide (CO2) versus high-frequency electroacupuncture based on the assistance of drilling and blunt dissection in the treatment of steatocystoma multiplex.Methods A randomized,self-controlled study was performed in 15 patients.The median line of the body served as the dividing line,and the lesions on the two sides of the median line of the body were randomly divided into 2 groups to be treated with CO2 laser or high-frequency electroacupuncture,which left micropathways into the cyst cavity.After the above treatment,contents in the cysts were squeezed out or drawn out with a mosquito clamp,and the cysts were bluntly dissected.The decrustation time,erythema subsiding time,adverse reactions and recurrence were compared among lesions at different sites or with different sizes.Results For the lesions at the same sites or with similar sizes after treatment,the decrustation time and erythema subsiding time were both significantly shorter in the CO2 laser group than in the high-frequency electroacupuncture group (both P ＜ 0.05).There were significant differences in the decrustation time and erythema subsiding time among lesions at different sites or with different sizes (all P ＜ 0.05).Mild pain occurred in the 2 groups,and no hematoma or secondary infection occurred.There were significant differences in the incidence of scar formation or pigmentation between the 2 groups (both P ＜ 0.05).During the follow-up of 6-18 months,relapse occurred in 1 patient in each group.Conclusion Compared with the high-frequency electroacupuncture,CO2 laser assisted by drilling and blunt dissection shows better efficacy in the treatment of steatocystoma multiplex,and it can remove lesions at various sites at one time.

Objective: To analyze the genome characteristics of an avian influenza A (H9N2) virus isolated from an 11-month-old infant, and to look for possible sources of infection. Methods: Throat swabs were collected from an infant with influenza-like illness in influenza sentinel surveillance hospitals and isolated for influenza viruses using cells. The isolates were identified for influenza virus types and subtypes by the method of hemagglutination assay, hemagglutination inhibition assay and fluorescence PCR. Whole genome sequencing of the isolated virus was carried out. The genome nucleic acid sequences and the deduced amino acid sequences were analyzed by comparing the phylogenetic trees which were constructed by bioinformatics software. Results: A seasonal un-typed influenza virus was isolated from the infant with influenza like illness. With fluorescent PCR method , it was identified as H9N2 subtype of avian influenza virus and the case was confirmed as a human infected with an avian influenza A(H9N2) virus. Epidemiological studies revealed that the case had no clear history of poultry contact and exposure. Blast analysis shows that eight segments of the viral genome are avian origin, and 97.5%-99.8% homology with that of viruses isolated from the live-poultry markets. The virus belongs to G57 genotype, deduced amino acid sequence analysis shows that the virus has typical low pathogenic avian influenza characteristics. Conclusions Although the case does not have a clear history of contact or exposure to poultry, molecular traceability suggests that possible sources of infection may be still from poultry.

Objective To evaluate the value of perioperative multimodal stratified analgesia guided by PPRS-CYMZ 2.0. Methods One hundred and sixteen patients of both sexes, aged 16-85 yr, of A-merican Society of Anesthesiologists physical statusⅠ-Ⅲ, scheduled for elective surgery in our hospital in August 2016, were included in this study and assigned into empirical analgesia group(group E, n=79) and stratified analgesia group(group S, n=73). The risk of postoperative pain was estimated by an expe-rienced associate chief anesthesiologist based on his clinical experience, and the perioperative analgesic protocol was determined in group E. The risk of postoperative pain was assessed using the perioperative pain risk scale PPRS-CYMZ 2.0 by another experienced associate chief anesthesiologist, the risk was stratified according to the scores, and the corresponding stratified analgesic protocol was determined in group S. Vis-ual analog scale scores and parents′satisfaction with analgesia were recorded on postoperative day 30. The requirement for preventive analgesia, total pressing times of patient-controlled analgesia(PCA)pump in 0-6 h, 6-24 h and 24-72 h periods, PCA background infusion dose and consumption of rescue analgesics were recorded. The development of adverse events during postoperative hospital stay and postoperative re-covery were also recorded. Analgesia-related parameters of medical economics were calculated. Results There was no significant difference in postoperative pain risk stratification between group E and group S(P>0.05), and the majority of patients were at moderate risk. Compared with group E, no significant change was found in visual analog scale scores on postoperative day 30, PCA background infusion dose or incidence of postoperative adverse effects(P>0.05), the requirement for preventive analgesia and satisfaction scores were significantly increased in high risk patients, the consumption of rescue analgesics was decreased in moderate risk patients(P<0.05), no significant change was found in the total pressing times of PCA pump in each time period in low risk patients(P>0.05), the total pressing times of PCA pump was significantly decreased, and the direct analgesic cost per patient and total analgesic cost were decreased in moderate and high risk patients, and the first ambulation time and length of postoperative hospital stay were shortened in high risk patients in group S(P<0.05). Conclusion PPRS-CYMZ 2.0 can achieve perioperative multi-modal stratified analgesia and individualized treatment.

OBJECTIVETo investigate the occupational health condition in a shipyard in Guangzhou, China, and to provide a basis for improving the working environment.

METHODSThe monitoring data on occupational harmful factors in the workplace and the data on health examination of the workers were analyzed, and the occupational health condition in the shipyard was evaluated with the related occupational health standards.

RESULTSExcept benzene, toluene, and electromagnetic radiation, the dust (2.02%), grinding wheel dust (3.85%), wood dust (2 out of 4 workers exceeded the standard), welding fume (16.85%), manganese dioxide (17.98%), dimethylbenzene (8.00%), and noise (53.20%) were all out of limits to different degrees. The health examination results of 2450 workers in the shipyard showed that the respiratory impairment of dust-exposed workers (3.19%) and the hearing impairment of noise-exposed workers (12.21%) were comparatively severe.

CONCLUSIONThe occupational health condition in this shipyard is not good. In order to protect the workers from health hazards, it is urgent and necessary to improve the working environment and strengthen the personal protective measures.

Air Pollutants ; Benzene ; China ; Construction Industry ; Dust ; Humans ; Noise ; Occupational Diseases ; Occupational Exposure ; Occupational Health ; Ships ; Surveys and Questionnaires ; Welding ; Workplace

Objective To evaluate the relationship between 18F-FDG uptake and P-gp expression in Bcap37 or Bcap37/MDR1 tumor-bearing BALB/c nude mice.Methods Bcap37 or Bcap37/MDR1 cells were injected into BALB/c nude mice (1× 107cells/ml,0.2 ml/mouse) to construct mice models.Bcap37 (n=5) or Bcap37/MDR1 (n=5) tumor-bearing mice fasted for 6 h before imaging.After anesthesia,the mice were injected with 7.4 MBq of 18F-FDG via tail vein.The dynamic microPET scans were carried out for 90 min.On the microPET images,the ROI was drawn and the TAC was obtained.The next day,those 10 mice underwent dynamic microPET scans after injected with elacridar (GF120918) and 18F-FDG.Another 10 mice,5 with Bcap37 tumors and 5 with Bcap37/MDR1 tumors,were used.After 7.4 MBq 18F-FDG with or without 2.0 mg/kg GF120918 was administered via tail vein,microPET images were acquired at 60 min.ROI was drawn over the tumors and SUV was obtained.Two-sample t test was used to analyze the data.Results GF120918 did not significantly alter the 18F-FDG accumulation curve in Bcap37 tumors,but significantly enhanced the 18F-FDG accumulation in Bcap37/MDR1 tumors.GF120918 did not influence 18F-FDG uptake (SUV) in Bcap37 tumors (1.052±0.028,1.028±0.045,t =1.792,P＞0.05),but significantly increased the SUV in Bcap37/MDR1 tumors (1.015±0.043,0.712±0.031,t=3.365,P＜0.05);The SUV of 18 F-FDG in Bcap37 tumors was significantly higher than that in Bcap37/MDR1 tumors without injection of GF120918 (t =3.952,P＜0.05).The SUV was not significantly different when GF120118 was injected (t=1.835,P＞0.05).Conclusions 18F-FDG is a substrate of P-gp.18F-FDG imaging combined with GF120918 injection may be an effective noninvasive method for the detection of tumor's MDR.

OBJECTIVETo establish a rat model of 1,2-dichloroethane (DCE)-induced subacute toxic encephalopathy.

METHODSSixty Sprague-Dawley rats were randomly divided into five groups: negative control, positive control, low-dose DCE (1 472 mg/m(3)), middle-dose DCE (2 550 mg/m(3)), and high-dose DCE (4 418 mg/m(3)). The three DCE groups received static inhalation of DCE 6 hours a day for 6 consecutive days. The positive control group received intraperitoneal injection of lipopolysaccharide (5 mg/kg) and were sacrificed 8 hours after injection. Blood and brain tissue were collected, followed by determination of brain water content and HE staining for pathological examination of brain tissue.

RESULTSThe rats in DCE groups suffered decreased body weight with increasing DCE dose (P < 0.01), and brain water content rose with increasing DCEdose. The brain water content of middle-dose DCE group (80.09 ± 0.14%) and high-dose DCE group (80.28±0.10%) increased significantly as compared with that of the negative control group (79.46±0.23%) (P < 0.001). Optical microscopy discovered loose structure and vasodilation in the brain tissue of middle-dose DCE group, indicating obvious brain edema; the high-dose DCE group and positive control group had spongiform and vacuolated brain tissues with severe vascular dilation, indicating severe brain edema.

CONCLUSIONA rat model of subacute toxic encephalopathy induced by 1, 2-dichloroethane has been successfully established.

Animals ; Disease Models, Animal ; Ethylene Dichlorides ; toxicity ; Male ; Neurotoxicity Syndromes ; Rats ; Rats, Sprague-Dawley