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Objective:To build a performance appraisal system for full-time researchers in specialized children′s hospitals, so as to mobilize their enthusiasm and improve their efficiency of scientific and technological output.Methods:Based on structure-process-result model, the library of indexes was initialized by such means as literature review and talent performance appraisal management experiences. From November 2020 to March 2021, Delphi method was adopted to finalize the appraisal indexes and weight of each index, while the quantifiable standards of the indexes were formulated by brainstorming, hence establishing the performance appraisal model index system for these researchers. Using both the new model and the original performance appraisal system of the hospital respectively, five full-time research staffs of research-oriented children′s hospital were selected for an empirical research on performance appraisal.Results:Fifteen experts carried out two rounds of Delphi research, finalizing a performance appraisal model for these researchers. The model comprises 3 level-1 indexes, 8 level-2 indexes and 23 level-3 indexes. Among them, the weight of scientific research output, scientific research process and scientific research investment of level-1 indexes were 0.507, 0.267 and 0.226, respectively. Empirical research showed that compared with the original appraisal indexes, the results of the new performance appraisal model were more targeted, enabling the research team to identify setbacks.Conclusions:The indexes set in the model built in this study prove more scientific, objective, and more reasonable in weight assignment. Such indexes can positively motivate and encourage the researchers, promoting the clinical-basic research integration, as well as the disciplinary development and research talent cultivation of the hospital.
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Chimeric antigen receptor T (CAR-T) cell therapy, which adoptively transfers engineered T cells expressing synthetic receptors to target specific antigens, has achieved great clinical success in treating hematological malignancies. Though FDA has approved two CAR-T products, CAR-T therapy can cause some side effects, such as cytokine release syndrome (CRS), neurotoxicity and B cell aplasia. Meanwhile, lacking tumor specific antigen and the suppressive tumor environment limit the efficacy of CAR-T therapy in solid tumor. This review focuses on the structural components, clinical applications and synthetic biology approaches on CAR-T cell design, and summarizes the challenges and perspectives of CAR-T therapy as a revolutionary cancer immunotherapy.
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Child , Humans , Cell- and Tissue-Based Therapy , Immunotherapy , Immunotherapy, Adoptive , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen , T-LymphocytesABSTRACT
Objective To determine the clinical characteristics of acute lower respiratory tract infections (ALRIs)induced wheezing,and to explore the impact of wheezing ALRIs on the subsequent respiratory diseases and lung function. Methods A total of 1726 hospitalized infants who were diagnosed with ALRIs in Children′s Hospital of Fudan University between March 2011 and February 2012 were enrolled and classified into wheezing group and non -wheezing group. Data were collected regarding demographic characteristics,family status,clinical presentations,respira-tory pathogens,and pulmonary function tests (PFTs). Subjects were followed up with questionnaires in 6 months and 1 year after discharge. PFTs were performed in 50 wheezing infants at 6 months after discharge. Results In the 1726 hospitalized infants,471 cases had a wheezing episode (27. 3％). The majority (262 / 471 cases,55. 6％)of infants with wheezing were reported with a family history of atopy. The total detection rate of viruses in wheezing group was 73. 7％ . The detection rate of respiratory syncytial virus (RSV)in wheezing group was higher than that of non-whee-zing group (68. 6％ vs. 47. 0％),and the difference was significant (P < 0. 001). For infants less than 3 months,the wheezing group had less time to peak tidal expiratory flow as a percentage of total expiratory time (TPTEF/ TE)and volume to peak tidal expiratory flow as a percentage of total expiratory volume (VPTEF/ VE),compared with the non -wheezing group [(22. 9 ± 9. 8)％ vs. (29. 2 ± 12. 3)％ and (25. 7 ± 8. 0)％ vs. (29. 8 ± 9. 6)％,respectively],and the differences were significant (all P < 0. 05). After 6 months,the wheezing group increased TPTEF/ TE and VPTEF/VE [(24. 0 ± 9. 0)％ vs. (19. 9 ± 6. 7)％,(25. 8 ± 7. 0)％ vs. (23. 2 ± 5. 0)％,respectively],and the differences were significant (all P < 0. 05),but still below normal level. Patients with wheezing were more likely to develop subse-quent wheezing during the following 1 year (20. 0％ vs. 10. 6％),and the difference was significant (P < 0. 001). Conclusion Wheezing in infants with ALRIs is related to family history of atopy and viral infections,especially to RSV. Hospitalization for wheezing ALRIs is associated with impaired lung function and a higher frequency of subsequent wheezing.
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AIM: To investigate the therapeutic effect of endothelial progenitor cell-conditioned medium (EPC-CM) on the lung structure of neonatal rat exposed to hyperoxia, and to explore the mechanisms.METHODS: Bone marrow-derived endothelial progenitor cells (EPCs) were collected from new born Sprague-Dawley (SD) rats and the EPCs were identified.The conditioned medium from the passage 3 EPCs was collected.Newborn SD rats (n=40) were randomly divided into 4 groups.The rats in room air group were exposed to the room air (21% O2) for 21 d.The rats in hyperoxia group were exposed to hyperoxia (85% O2) for 21 d.The rats in endothelial cell basal medium (EBM) group were exposed to hyperoxia for 21 d, and received 100 μL EBM on postnatal day 14 (P14) in a single intratracheal (IT) injection.The rats in EPC-CM group were exposed to hyperoxia for 21 d, and received 100 μL EPC-CM on P14 in a singlie IT injection.The rats were sacrified on the 21st day.The left lungs were excised, placed in 4% paraformaldehyde, serially dehydrated in ethanol and embedded by paraffin.Serial sectioning of the paraffin-embedded left lung tissues was prepared for 5 μm thickness, and stained with hematoxylin and eosin.The pulmonary radical alveolar count (RAC) and alveolar mean linear intercept (MLI) were then calculated.The microvascular density was determined by FVIII immunostaining.The mRNA expression of KGF, VEGF, SP-A and SP-C in the right lung tissues was detected by real-time fluorescence quantitative PCR.RESULTS: The cultured cells had typical EPC morphological characteristics, and had the abilities to bind to FITC-UEA-1 and uptake DiI-ac-LDL.The body weight of the rats on day 21, RAC, MLI and microvascular density were significantly lower in hyperoxia group and EBM group than those in room air group (P<0.05).The EPC-CM group had significantly higher RAC and microvascular density than those in hyperoxia group and EBM group (P<0.05), but the body weight and MLI had no significant difference.The mRNA expression levels of KGF, VEGF, SP-A and SP-C in hyperoxia group and EBM group were significantly lower than those in room air group (P<0.05).The mRNA expression levels of KGF, VEGF, SP-A and SP-C in EPC-CM group were significantly higher than those in hyperoxia group and EBM group (P<0.05).CONCLUSION: EPC-CM promotes the lung alveolarization and microvascular formation in neonatal rats exposed to hyperoxia.These benefits may be correlated with the increased KGF and VEGF mRNA expression.
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Objective To study the effect of transplanted endothelial progenitor cell (EPC) on hyperoxia-induced lung injury in neonatal rats.Methods Rat bone marrow mononuclear cells were cultured in endothelial cell growth medium to obtain EPCs,which were identified by morphology,phagocytosis and CD34+ analyses.Sixty neonatal Sprague-Dawley rats were allowed to acclimate in room air for 24 h after birth,and were then divided into four groups (15 per group),including the air group,the hyperoxia group,the EPCs transplantation group and the N ω-nitro-L-arginine methyl ester (L-NAME) intervention group.Neoborn rats in the Air and Hyperoxia groups were fed in the room air or hyperoxia (85％ oxygen) for 28 days.For rats in transplantation group were exposed continuously to hyperoxia for 28 days,and got an EPC (1 × 105 cells) injection on the 21st day.Rats in Intervention group were exposed continuously to hyperoxia for 28 days,got an EPC (1 × 105 cells) injection on the 21st day,and a daily injection of L-NAME from day 21 to day 28,with a daily dose of 20 mg/kg.Levels of circulating CD34+ cells and serum VEGF expression were detected.Specimens from lung tissues were analyzed by immunohistochemistry or immunofluorescence.The expression of vascular endothelial growth factor (VEGF),VEGF receptor 2 (VEGFR2) and eNOS were detected by realtime polymerase chain reaction and Western-blotting.NO production were detected by nitrate reductase assay.One way ANOVA and Bonferroni test were used for statistical analysis.Results (1) The cultured cells had a typical cobblestone appearance; double positive cell binding of fluorescein Ulex Europaeus agglutinin-1 and uptake of Dil-labeled acetylated low density lipoprotein accounted for approximately 85％ of the total number of cells.CD34+ cells accounted for 68.2％-72.4％ of total cultured cells.(2) Circulating CD34+ cells in the air group,hyperoxia group,EPC transplantation group and L NAME intervention group were (1.91 ± 0.34)％,(1.06 ± 0.10)％,(1.47 ± 0.06)％ and (0.77 ± 0.11)％ (F=32.710,P=0.000).The number of circulating CD34+ cells in the hyperoxia group was lower than the air group,in the EPC transplantation group the number of these cells was higher than the hyperoxia group,and in the L-NAME intervention group the number of these cells was lower than that in the EPC transplantation group,and the differences between these two groups were statistically significant (P ＜ 0.05,respectively).Serum VEGF in the four groups was (7.90±2.72),(6.38±0.72),(14.00± 1.66) and (11.70± 1.91) pg/ml,respectively.The difference between the four groups was statistically significant (F=22.809,P=0.000),and serum VEGF in the EPC transplantation group was higher than that in the hyperoxia group (P ＜ 0.05).(3) Transplanted EPCs could engraft in pulmonary vascular endothelium and alveolar interstitium,and L-NAME intervention significantly reduced the engraftment of EPCs in the lungs (10.7±0.47 / field vs 16.95±0.5 /field,t=17.820,P=0.000).(4) There were significant differences in the radial alveolar count (RAC) and number of microvessels between the four groups (F=859.580 or 211.150,P=0.000,respectively).RAC and the number of microvessels in the hyperoxia group were less than those in the air group (7.98±0.23 vs 13.12±0.20,3.98±0.42 vs 9.50±0.22,P ＜ 0.05,respectively).The number of microvessels in the EPC transplantation group was 5.40±0.41,being higher than that in the hyperoxia group (P＜0.05).(5) VEGF mRNA in lungs in the hyperoxia group was lower than that in the air group (0.23 ± 0.16 vs 1.05 ± 0.33,P ＜ 0.05); in the EPC transplantation group,VEGF mRNA was higher than that in the hyperoxia group (0.69 ± 0.09 vs 0.23 ± 0.16,P ＜ 0.05); and in the L-NAME intervention group,VEGF mRNA was lower than that in the EPC transplantation group (0.31 ±0.08 vs 0.69±0.09,P ＜ 0.05).VEGF protein in the lungs in the hyperoxia group was lower than the air group (0.52±0.01 vs 0.82±0.01,P ＜ 0.05),and was higher in the EPC transplantation group than the hyperoxia group (0.58±0.05 vs 0.52±2501,P ＜ 0.05).VEGFR2 mRNA in the hyperoxia group was lower than the air group (0.35±0.13 vs 1.07±0.45,P ＜ 0.05).eNOS mRNA in the hyperoxia group was lower than the air group (0.46±0.10 vs 1.05±0.36,P ＜ 0.05).eNOS protein in the hyperoxia group was lower than the air group (0.32±0.01 vs 0.51 ±0.03,P ＜ 0.05),and was higher in the EPC transplantation group than the hyperoxia group (0.86±0.02 vs 0.32±0.01,P ＜ 0.05).Conclusion Transplanted EPC can engraft in the lung tissue,improving alveolar and pulmonary vascular development,which may be associated with upregulation of the expression of eNOS and VEGF in lung.
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Funds management,which has a direct effect on the development of scientific research projects,is an important part of the scientific research management in hospitals.By investigating the present situation of the scientific research funds management in a local hospital in Shanghai,this paper analyzes the problems commonly found in the scientific research funds management.Based on the findings of the analysis,this paper proposes some corresponding recommendations and countermeasures to improve the management.
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<p><b>OBJECTIVE</b>To investigate the clinical epidemiologic characteristics and analyze risk factors for acute respiratory syncytial virus (RSV) infection in hospitalized infants with acute lower respiratory tract infection (ALRI).</p><p><b>METHOD</b>ALRI infants admitted to Children's Hospital of Fudan University from March 1st, 2011 to February 29th, 2012, were enrolled in this study. Patient information included demographic characteristics, feeding history, family status, clinical presentation, accessory examination, treatment and prognosis. According to the etiology of ALRI infants, we compared the seasonal distribution, demographic characteristics, household characteristics and underlying diseases between RSV-positive patients and RSV-negative patients. Univariate and multiple Logistic regression analyses were used to determine factors that were associated with risk of RSV infection.</p><p><b>RESULT</b>Among 1 726 ALRI infants, there were 913 RSV-positive infants (52.9%). The occurrence of RSV infection had a seasonal variation, with a peak in winter (59.1%). The median (P25, P75) age of RSV infants was 64 (21-155) days. The gestational age (GA) and body weight (BW) was (37.5 ± 2.4) weeks and (3.07 ± 0.66) kg, respectively. The male/female ratio among these was 1.9: 1. RSV infection was more popular among infants in the families with smoking members, crowded living conditions, history of atopic mother. Differences of the proportion of patients with underlying disease between RSV-positive and negative groups were statistically significant (59.4% vs. 54.2%, P < 0.05). Univariate logistic regression demonstrated that factors increasing the risk of RSV infection were: GA<37 weeks (OR = 1.346, 95%CI: 1.037-1.748), birth weight <2 500 g (OR = 1.447, 95%CI: 1.103-1.898), underlying diseases (OR = 1.232, 95%CI: 1.018-1.492), underlying CHD (OR = 1.391, 95%CI: 1.120-1.728), environmental tobacco smoke exposure (OR = 1.254, 95%CI: 1.035-1.519), mother with atopic diseases (OR = 1.827, 95%CI: 1.296-2.573), crowded house with four or more than four family members (OR = 1.232, 95%CI: 1.013-1.498), autumn or winter infection (OR = 1.351, 95%CI: 1.024-1.783; OR = 1.713, 95%CI: 1.332-2.204). Multivariate logistic regression determined the factors increasing the risk of RSV infection were: underlying CHD (OR = 1.298, 95%CI: 1.002-1.681), mother with atopic diseases (OR = 1.766, 95%CI: 1.237-2.520), autumn or winter infection (OR = 1.481, 95%CI: 1.105-1.985; OR = 1.766, 95%CI: 1.358-2.296).</p><p><b>CONCLUSION</b>The prevalence of RSV infection was the highest in winter, while preterm and low birth weight infants were more susceptible. Underlying diseases were found in 59.4% cases, CHD was the most common one. The factors increasing the risk of RSV infection were: CHD, mother with atopic diseases, autumn or winter infections.</p>
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Female , Humans , Infant , Infant, Newborn , Male , Acute Disease , China , Epidemiology , Environmental Exposure , Hospitalization , Logistic Models , Prevalence , Respiratory Syncytial Virus Infections , Epidemiology , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Epidemiology , Virology , Retrospective Studies , Risk Factors , Seasons , Socioeconomic Factors , Tobacco Smoke PollutionABSTRACT
<p><b>OBJECTIVE</b>Body plethysmography is a typical method to measure functional residual capacity (FRC) and airway resistance (Raw). The aim of the study was to test the feasibility of measuring lung function with the body plethysmography in young children with acute lower respiratory tract infection (ALRI) by evaluating changes and prognosis of lung function for infants with ALRI with or without wheezing via body plethysmograph.</p><p><b>METHOD</b>Pulmonary function tests (PFTs) were performed by using body plethysmography in 444 children with ALRI, aged 1-36 months, to assess their tidal breathing parameters such as ratio of time to peak tidal expiratory flow to total expiratory time (TPTEF/TE), ratio of volume to peak tidal expiratory flow to total expiratory volume (VPTEF/VE), plethysmographic functional residual capacity (FRCP), FRCP per kilogram (FRCP/kg), specific effective airway resistance (sReff), effective airway resistance (Reff), Reff per kilogram (Reff/kg), etc. According to whether there was wheezing or not, children who had ALRI with wheezing were classified as Group-W, or without wheezing as Group-N. Changes or correlations of tidal breathing parameters and plethysmographic parameters were compared.One hundred and three contemporaneous healthy controls aged 1-36 months underwent the same tests for comparison. And 36 wheezing children accepted PFTs at follow-up in recovery phase.</p><p><b>RESULT</b>Mean values of TPTEF/TE in Group-W,Group-N and the Control respectively were (20.5 ± 6.7)%,(22.8 ± 6.5)%,(34.6 ± 5.0)% (F = 110.500, P < 0.001), while VPTEF/VE respectively were (23.0 ± 6.3)%,(25.2 ± 6.8)%,(34.5 ± 4.2)% (F = 107.800, P < 0.001). Compared to the Control,Group-W and Group-N had significantly higher values of FRCP (226 vs. 176 vs. 172 ml, χ(2) = 64.870, P < 0.001), FRCP/kg(24.40 vs.17.80 vs.17.60 ml/kg,χ(2) = 68.890, P < 0.001), sReff(1.00 vs. 0.52 vs. 0.46 kPa·s,χ(2) = 75.240, P < 0.001), Reff (3.90 vs.2.74 vs.2.20 kPa·s/L, χ(2) = 36.480, P < 0.001) and Reff/kg [0.42 vs. 0.29 vs.0.22 kPa·s/(L·kg), χ(2) = 29.460, P < 0.001]. Although 25 (12.8%) wheezing children with ALRI had normal values of tidal breathing parameters, they already had increased FRCP, FRCP /kg, sReff, Reff and Reff/kg (t = 2.221, 1.997, 2.502, 2.587, 2.539, all P < 0.05). Values of FRCP and Reff in infants caught ALRI were inversely correlated to that of TPTEF/TE and VPTEF/VE (P < 0.05); 36 children with wheezing who accepted PFTs at follow-up had shown significant decline in the specific parameters of plethysmography such as FRCP, FRCP/kg, sReff, Reff and Reff/kg (Z = -1.999, -2.195, -2.038, -1.823, -2.054, all P < 0.05), while no improvement in the main parameters of tidal breathing such as TPTEF/TE.</p><p><b>CONCLUSION</b>Measuring lung function with the body plethysmography in young children with ALRI is feasible. FRC and Raw, as special lung function testing parameters of body plethysmography, were sensitive indicators reflecting impairment of lung function in infants with ALRI (especially for children caught ALRI with wheezing) and shows significant correlation with parameters from lung function testing via tidal breathing. Therefore plethysmography is worthy of clinical promotion.</p>
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Child, Preschool , Female , Humans , Infant , Male , Airway Resistance , Physiology , Case-Control Studies , Functional Residual Capacity , Physiology , Lung , Plethysmography, Whole Body , Respiratory Function Tests , Respiratory Sounds , Diagnosis , Respiratory Tract Diseases , Diagnosis , Tidal VolumeABSTRACT
ObjectiveTo establish a method for measuring exhaled nitric oxide (eNO)concentrations in neonates with and without hypoxemic respiratory failure ( HRF), and to investigate the relationship between eNO and respiratory parameters in neonates with HRF. Methods Twenty-two newborn infants with HRF and 26 control neonates were included within the first 24 hours of postnatal life.Their eNO levels were detected with a rapid-response chemiluminescence analyzer daily during the first week of their postnatal life, and lung mechanics and gas exchange efficiency were monitored at the same time, such as pulse oxygen saturation ( SpO2 ), inspired fraction of oxygen ( FiO2 ) and other parameters.Wilcoxon Mann-Whitney U tests were used to compare eNO, SpO2/FiO2 and eNO/ ( SpO2/FiO2 × 100) in two groups. Pearson's correlation analyses were used to determine the relationships between eNO levels and indices of hypoxemic respiratory failure. ResultsDuring the first two days of postnatal life, eNO values of HRF neonates were higher than those of the control neonates[day 1,(7. 9 ± 3.2 )× 10-9 vs. (5.8 ±1.8)×10-9, P＜0.05;day2, (8.8±3.2)×10-9vs. (6.0±2.4)×10-9, P＜0. 05], butthere were no significant differences in the following days. With SpO2/FiO2 increasing, difference of eNO values between the HRF and non-HRF controls became narrowed, but there was still two fold difference of eNO/(SpO2/FiO2 × 100) on day 5-7. ConclusionsA method for measuring eNO was established and there was difference in neonates with and without HRF, which diminished with prolonged postnatal days, reflecting pathophysiological characteristics of HRF.
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Objective To establish a method of isolation, purification and identification of type Ⅱ alveolar epithelial cells (AEC- K ) from neonate piglet lungs of 1 ～ 3 days old and to investigate effects of proinflammatory cytokines on expression of growth factors (GFs). The yield, viability and purity of AEC- Ⅱ obtained using different enzyme digestion and purifying methods were compared. Methods After the first 24-hour culture of AEC- Ⅱ ,the media containing interleukin (IL)-1β,IL-6 and IGF-Ⅰ at different concentrations were used to culture AEC-Ⅱ for another 48 hours. And then the cells were counted and the expressions of insulin-like growth factor (IGF-Ⅰ ), platelet-derived growth factor ( PDGF), surfactant proteins (SP) -A and SP-B mRNA were determined by real time PCR. Results A significantly higher yield of AEC-Ⅱ was achieved by digesting the lung with 30 unit/ml elastase and 0.1 % trypsin at 37 t for 20 min, the yield was (5.33 ±0.54) × 106 after adjusted by the weight of lung and heart (P <0.01). The number of purified AEC-II obtained by immune adherence method was (38.0 ±28.0) × 106 perpiglet which was higher than by the method of percoll. The optimal phenotype maintenance time of AEC- Ⅱ was the first 24～96 hours in the primary culture. With increasing concentrations of IL-1 β and IL-6, there were decreased proliferation and expression of SP-A and IGF-Ⅰ mRNA in the cultured AEC- Ⅱ ,but SP-B mRNA expression was not affected. Both AEC-Ⅱ proliferation and expression of SP-A, SP-B mRNA decreased significantly after cultured with anti-IGF-Ⅰ. Conclusion In a new model of cultured AEC-Ⅱ from neonate piglets, IL-1β and IL-6 inhibited AEC- Ⅱ proliferation and SP-A mRNA expression through IGF-Ⅰ -dependent mechanisms.
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Objective To explore the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in hyperoxia-induced lung injury in preterm rats. Methods At the 2 nd postnatal day Sprague-Dawley preterm rats were randomly assigned to air group and hyperoxia group (exposed to about 85% of O 2). At 3,7,14 and 21 days after exposure, six rats of each group were used to assess lung histologic changes and expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in lungs by immunohistochemistry. At 3,7 and 14 days after exposure, gelatinase activity in bronchoalveolar lavage fluid (BALF) of another six rats in each group by gelatin zymography was examed. Results Except 3 d after exposure, hyperoxia group showed lung injury characterized by subacute alveolitis and inhibition of lung development. Expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in hyperoxia group was stronger than that in air group at every time (P