Objective:To standardize the management of pediatric Investigator-Initiated Trails (IIT) and improve the execution quality, this study takes a tertiary hospital for children in Shanghai as an example to analyze and summarize the main quality problems in the implementation of pediatric IIT projects and provide appropriate suggestions.Methods:From 2020 to 2022, based on the quality indicators of the IIT project of Shanghai Jiao Tong University School of Medicine, and combined with the characteristics of pediatrics, a centralized monitoring method was used to conduct spot checks and evaluations on the IIT project of a tertiary hospital for children in Shanghai.Results:From 2020 to 2022, a total of 77 IIT projects were inspected, including 27 in the initiation stage, 36 in the execution stage, and 14 in the conclusion stage. In terms of ethical compliance, there are issues with researchers′ weak ethical awareness and non-standard signing of informed consent in the pediatric IIT project. The main problems in terms of execution quality and science include non-standard CRF table design, insufficient awareness of safety management, lack of emphasis on research registration and specialized data management, randomization and blind methods. There are issues with low enrollment rate and low funding execution rate in terms of execution progress.Conclusions:There are certain quality problems during the execution of pediatric IIT projects. Strengthen the establishment of an effective process management and supervision system to improve the quality management of pediatric IIT research processes is needed.

Objective:To construct a drug knowledge base based on drug instructions.Methods:Six hundred randomly selected drug instructions were labeled manually and divided into training set and test set. The training was based on bidirectional long short-term memory(Bi-LSTM) and conditional random fields(CRF) model to complete the recognition of medical entities. The extracted entities were standardized by the hybrid model of " similarity calculation and rule mapping table" , and then the drug information was imported into the Access database.Results:In the task of named entity recognition based on Bi-LSTM and CRF model, except for the crowd entities, the other entities had achieved good results with an F-value higher than 85%. Based on the hybrid model of " similarity calculation and rule mapping table" , the accuracy of entity standardization was 88.23%.Conclusions:The effect of the machine learning model in this study is similar to that of other named entity recognition and entity standardization studies, which can complete the task of drug knowledge base construction satisfactorily.

Objective:To explore the influence of hypophosphatemia on weaning from mechanical ventilation.Methods:An observational study was conducted. The medical records of 30 mechanical ventilated patients with hypophosphatemia admitted to intensive care unit of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to August 2020 were analyzed; another 60 mechanical ventilated patients with normophosphatemia around the same time were enrolled as controls by 1∶2 case-control matching based on gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score. And then the duration of invasive mechanical ventilation, times of spontaneous breathing trial (SBT), the diaphragmatic ultrasonography movement indexes, and outcome of weaning and prognosis during hospitalization were compared between the two groups. Receiver operator characteristic curve (ROC curve) was plotted to calculate the areas under ROC curve (AUC) and cut-off values of serum phosphorus for successful weaning and hospital survival. The correlations between the diaphragmatic ultrasonography movement indexes and serum phosphorus were analyzed by Pearson partial correlation analysis.Results:Compared with normophosphatemic group, the duration of invasive mechanical ventilation in hypophosphatemia group was significantly longer [days: 13.0 (7.0, 22.0) vs. 10.0 (5.5, 14.0), P < 0.05], and SBT attempts were more often [times: 3 (0, 5) vs. 1 (1, 2), P < 0.01], while the rate of successful weaning was lower (53.3% vs. 91.7%, P < 0.01), and the hospital mortality was higher (20.0% vs. 1.7%, P < 0.01). ROC curve analysis showed that serum phosphorus could predict successful weaning of mechanical ventilated patients, the AUC was 0.795, and the optimum cut-off value of serum phosphorus was 0.85 mmol/L with sensitivity of 73.2% and specificity of 84.2%. Serum phosphorus could predict hospital survival of mechanical ventilated patients, the AUC was 0.782, and the optimum cut-off value of serum phosphorus was 0.48 mmol/L with sensitivity of 81.9% and specificity of 85.7%. Compared with normophosphatemic group, diaphragm thickness at the end of inspiration (DTei), diaphragm thickness at the end of expiration (DTee), diaphragm thickening fraction (DTF), diaphragm excursion (DE) in hypophosphatemia group were all significantly decreased [DTei (cm): 0.19±0.07 vs. 0.27±0.08, DTee (cm): 0.14±0.05 vs. 0.19±0.06, DTF: (33.55±16.17)% vs. (45.04±18.66)%, DE (cm): 1.17±0.49 vs. 2.28±0.69, all P < 0.01]. Pearson partial correlation analysis showed that linear correlations were found between serum phosphorus and DTei, DTee, DTF, DE ( r values were 0.442, 0.351, 0.293, 0.628 respectively, all P < 0.01). Conclusions:Serum phosphorus may have correlation with the diaphragmatic ultrasonography movement indexes. Hypophosphatemia may impair the contractile properties of diaphragm, induce more SBT attempts and longer duration of invasive mechanical ventilation, and affect outcome of weaning and prognosis.

PURPOSE: Developing a risk prediction model for invasive fungal disease based on an analysis of the disease-related risk factors in critically ill patients in the intensive care unit (ICU) to diagnose the invasive fungal disease in the early stages and determine the time of initiating early antifungal treatment. METHODS: Data were collected retrospectively from 141 critically ill adult patients with at least 4 days of general ICU stay at Sun Yat-sen Memorial Hospital, Sun Yat-sen University during the period from February 2015 to February 2016. Logistic regression was used to develop the risk prediction model. Discriminative power was evaluated by the area under the receiver operating characteristics (ROC) curve (AUC). RESULTS: Sequential organ failure assessment (SOFA) score, antibiotic treatment period, and positive culture of Candida albicans other than normally sterile sites are the three predictors of invasive fungal disease in critically ill patients in the ICU. The model performs well with an ROC-AUC of .73. CONCLUSION: The risk prediction model performs well to discriminate between critically ill patients with or without invasive fungal disease. Physicians could use this prediction model for early diagnosis of invasive fungal disease and determination of the time to start early antifungal treatment of critically ill patients in the ICU.
Adult ; Candida albicans ; Critical Care* ; Critical Illness* ; Early Diagnosis ; Humans ; Intensive Care Units* ; Logistic Models ; Retrospective Studies ; Risk Factors ; ROC Curve ; Solar System

Objective To investigate the effect of precondition with Toll-like receptor 4 monoclonal antibody (TLR4mAb) on lipopolysaccharide (LPS) -induced acute lung injury in mice.Methods A total of 45 male BALB/c mice were randomly divided into 3 groups:the control group ( group C),the sepsis group (group S) and the pretreatment group (group P).Mice in the group P and group S were injected intraperitoneally with LPS ( 10 mg/kg) to produce acute lung injury models.Mice in the group P was injected intraperitoneally with TLR4mAb (5 μg/g) 1 h before the injection of LPS.Expression of TLR4mRNA in lung tissue,expression of TNF-α and IL-6 in serum,water content of lung,and the pathomorphologic changes of lung were detected after 6 h,12 h and 24 h.One-way ANOVA was used for inter-group comparison and two-way ANOVA was used for intra-group comparison.Results Compared to group C,water content significantly increased at 12 h and 24 h in group S and group P; compared to group S,water content significantly decreased in group P at 12 h and 24 h.Compared to group C,the expression of IL-6 and TNF-α significantly increased in group S and group P at 6 h,12 h and 24 h; compared to group S,the expression of IL-6 and TNF-α significantly decreased at 6 h,12 h and 24 h in group P.Compared to group C,the expression of TLR4 mRNA increased significantly in group S and group P at 6 h,12 h and 24 h; compared to group S,the expression of TLR4 mRNA decreased significantly in group P at6 h,12 h and 24 h.Compared to group S,pathological damage of the lung was improved significantly in group P.Conclusions Precondition with TLR4mAb can attenuate LPS-induced acute lung injury,suppress the expression of inflammatory factors.Regulation of TLR4 pathway may be a promising therapeutic strategy for ALI.

Objective To verify whether the concomitant performance of modified radical inguinal lymphadenectomy and penectomy may increase complications and compromise oncological effectiveness.Methods From June 2002 to June 2010,a total of 110 simultaneous inguinal lymphadenectomies were performed on 55 patients (mean age 49 years),including 107 modified radical lymphadenectomies,2 radical lymphadenectomies and 1 lymphadenectomy before which the sapheous vein was resected.The records of all patients were reviewed.Results Of 107 simultaneously modified radical inguinal lymphadenectomy,only 1 (0.9％) had wound infection.There were 18 ( 16.8％ ) leg lymphedema and 6 (5.6％) skin flap necrosis,postoperatively.The average number of inguinal lymph nodes dissected was 11 (3 -23 ).Overall 3-year survival was 84％.Conclusions Penile surgery combined with simultaneously modified radical inguinal lymphadenectomy could be feasible,which may have oncological control without increasing the risk of surgical complications.

Objective To report a modified radical inguinal lymphadenectomy the aim of which is to reduce the incidence of the complication of skin necrosis.Methods One hundred and twenty-six modified radical inguinal dissections were performed in 63 patients with penile carcinoma from June 2002 to June 2010.A modified radical inguinal dissection characterized by an S-shaped incision and precisely separating layers using an anatomical mark was performed.The boundaries of dissection were the same as classic radical inguinal lymphadenectomy.The incidences of complications of skin flap necrosis were retrospectively analyzed.Results The follow-up time ranged from 12 to 93 months.A total of 37 complications occurred,including 7 minimal skin necroses (5.6％),3 wound infections (2.4％),19 lymphedemas (15.1％),2 seroma formations (1.6％),5 lymphocele (4.0％),and 1 deep venous thrombosis (0.8％).There were no complications in 106 dissections (84.1％ ),and 20 dissections had one or two minor complications ( 15.9％ ).Conclusions The complication of skin necrosis related to groin dissection in patients with penile carcinoma could be reduced by using this modified inguinal dissection technique,which characterized by an S-shaped incision and precisely separating layers with using an anatomical landmark.

Objective To explore the effect of glutamine on changes in the expression of intercellular adhesion molecule-1(ICAM-1)and E-selectin and the characteristics of pulmonary vascular endothelial cells(VECs)in sepsis rats.Method Totally 56 Sprague-Dawley rats were randomly divided into three groups:a control group,a sepsis group and a treatment group.All experiments were performed at the animal research center at Sun Yat-sen University in Guangzhou.Sepsis was induced by injecting 4 mg/kg lipopolysaccharide(LPS).The treatment group was injected with 4 mg/kg LPS and 0.3 g/kg glutamine.The control group was not injected with either LPS or glutamine.The rats were killed at 6,12 or 24 h after treatment and pulmonary tissue samples were obtained.The expression of ICAM-1 and E-selectin in VECs was detected by reverse transcription-polymerase chain reaction and immunohistochemistry.Apoptosis of VECs lung tissue was analyzed by Hoechest-33258 staining.The ultramicrostructure of VECs was observed under an electron microscope.Data were analyzed using analysis of variance using SPSS 13.0.Results At 6,12 and 24 h,the expression of ICAM-1 and E-selectin was significantly higher in the sepsis group(relative expression;ICAM-1:0.0864 ± 0.0101,0.141 ± 0.0147 and 0.1677 ± 0.0127,respectively;E-selectin:0.1535 ±0.0180,0.0811 ±0.0107 and 0.0505 ± 0.0031,respectively)compared with the control group(ICAM-1:0.021 ±0.0032,0.0228±0.0042 and 0.0204±0.0059,respectively;E-selectin:0.0423 ±0.0108,0.0412 ±0.0066 and 0.0418 ±0.0092,respectively)(all:P＜0.01).Glutamine treatment significantly decreased(P＜0.01)the expression of ICAM-1(0.0646±0.0136,0.1202±0.0143 and 0.1378 ±0.0085,respectively)and E-selectin(0.1071 ±0.0189,0.0628±0.0088 and0.0463±0.0049,respectively)at all time points compared with the sepsis group.However,the expression of ICAM-1 and E-selectin remained significantly higher than that in the control group(all:P＜0.05).There were similar changes in the expression of pulmonary ICAM-1,E-selectin mRNA and the results of VEC apoptosis.Electron microscopy confirmed these findings.Conclusions The expression of ICAM-1 and E-selectin was significantly increased in sepsis rats,leading to necrosis and apoptosis of VECs,and the onset of acute lung injury.Glutamine had a protective effect in VECs against lipopolysaccharide-induced sepsis.

Objective To explore the changes of matrix metalloproteinase-9 and blood brain barrier in cardiopulmonary resuscitation rats and effects of MMP-9 inhibitor on them.Method One hundred and twenty Sprague-Dawley(SD) rats were randomly divided into 3 groups:the sham-operated group,the resuscitation with treatment group and the resuseimfion without treatment group as control.The experiment was made in the animal experiment center of Sun Yat-sen University in Gtlangzhou.The rat eardiopulmonary resuscitation model was made by clipping trachea until asphyxia,and the restoration of spontaneous circulation(ROSC)Was defined by restoration of superventricular rhythm and mean artery pressure (MAP)≥60 mmHg for more than 5 min utes.The rats of sham-operated group were anesahetized only and endotracheal intubation WaS performed.In the resuscitation with treaUnent group ss-3cr(25,ng/ks body weight)Was given intraperitoneally after ROSC.The rats were sacrificed and samples of the brain tissue were taken inmaediately and 3 h,9 h,24 h and 48 h later.After that,the expression of MMP-9 and MMP-9 mRNA in brain tissue were detected.Water oontent and Evans blue in brain tissue Were observed.The uhmmicrostructure of brain tissue was observed under electron microscope.Analysis ofvariance wilE, done with Spssll.0 software.Results 11le expressions of MMP.9 and MMP-9m RNA ofbraintissueiUthe shanloperated group didn't show significant changees in all specimens taken at different intervals and neither the water content and tvans blue did.The Pvalue were 1.0000,0.6831,0.7124 and 0.99r75,respectively.There was no u1.tramicrostruclure change in the sham-operated group.The expressions of MMP_9 and MMP-9 mRNA in the resuscitation control group obviously increased after eardiopulmonary resuscitation,80 did the water content and Evans blue content.Compared with sham-operated group,the P value were 0.0264,0.0163,0.0000 and 0.0412,respee.tively.111e elge of ultmmicrostmeture in the resuscitation control group at different intervals were obvious.The changes of obove biomarkers in the resuscitation treatment group Was siroilar to but less in magnitude than those in the resuscitation control group.The P valHe were 0.0392,0.0373,0.O004 and 0.0180,respectively.Conclusions The expressions of MMP-9 and MMP.9 mRNA obviously increases in the cerebral ischemia model of rats with CPR,and reaches peak at 24 h.Water content and Evans blue content in brain risque obviously increases in the cerebral ischemia model of rats with CPR.BBB iS destroyed.and the peak time iS at 24 h.The injury of ultrami.crostructure of brain tissue under electron microscope iS obvious,and the peak time is at 24 h.The SB-3CT.specif-iC inhibitor of MMP-9 could decrease the expression of MMP-9 and decrease cerebral edema in the cerebral is.chemia modeJ of rats with CPR,and the protection from cerebral isehemia/reperfusion injury after CPR is obvious.

Objective:To observe the changes and significance of pulmonary vascular endothelial cells (VEC),ICAM-1 and E-selectin in sepsis rats.Methods:60 SD rats were randomly divided into 2 groups:the control group and the sepsis group.The sepsis model was prepared by injection of lipopolysaccharide(4 mg/kg).The expression of ICAM-1 and E-selectin in pulmonary VEC of rats was detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical method.The VEC apoptosis in lung was analyzed with Hoechest-33258 staining.The ultramicrostructure of pulmonary VEC was observed under electron microscope.Results:Compared with the control group,the expression of ICAM-1 was significantly increased in the sepsis group (P<0.01),the expression of ICAM-1 was increased gradually and achieved the peak value at 24 h.The expression of E-selectin was achieved the peak value at 6 h and decreased gradually during 24 h.The apoptosis and necrosis of pulmonary VEC was increased gradually and achieved the peak value at 24 h (P<0.01).Conclusion:The expression of ICAM-1 and E-selectin in sepsis rats is significantly increased,probably leading to both necrosis and apoptosis of pulmonary VEC,resulting in the occurrence of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).