Objective To construct machine learning models that can be used to predict AUC fold change(FC)using a database of existing pharmacokinetic(PK)and drug-drug interaction(DDI)information,which can be used to explore the possibility of predicting existing drug interactions and to provide certain rational recommendations for clinical drug use.Methods PK data of DDIs and AUC fold change data were extracted from FDA-approved drug labels.Peptide and pharmacodynamic(PD)information related to drug interactions were retrieved through DrugBank,and PPDT identification of relevant peptide IDs was performed using Protein Resource(UniProt),and a matrix normalization code was used to generate multidimensional vector data that were easy to analysis.The effect of PPDT on the AUC,and the resulting multiplicity change was used as the dependent variable for machine learning model construction.The model with the smallest root mean square error(RMES)value was used for model construction to train a bagged decision tree(Bagged)prediction model.The models were tested using the trained models for some of the drug tests.The models were evaluated by reviewing the available literature findings on detection of drug interaction pairs and analyzing and comparing the predicted values.Results A total of 16 pairs of model drug pairs were tested for the effects of 16 drugs on tacrolimus,and it was found that the accuracy of the prediction of the presence or absence of drug interactions was 81.25％;the prediction results were classified according to the FDA standard classification of the strong and weak for the strength of drug interactions,and the results showed that the prediction of the strength of drug interactions,with a large deviation from the larger prediction was less.Conclusion The evaluation of the model to predict the presence or absence of drug interactions was general;however,after classifying the strengths and weaknesses of drug interactions,the prediction of drug interactions was better,and the prediction results indicated that the model prediction performance has a certain reference value for potential DDI assessment before clinical trials.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

OBJECTIVE: To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT). METHODS: The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed. RESULTS: Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G^-) bacteria (62.8%), 40 Gram-positive (G⁺) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G⁺ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001). CONCLUSION The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;
Bacteremia/epidemiology* ; Bacteria ; Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies ; Sepsis

Objective: To evaluate the effectiveness and safety of Pul-Stent as the treatment of postoperative branch pulmonary artery stenosis in children with congenital heart disease. Methods: This was a retrospective study. Thirty-three patients who underwent Pul-Stent implantation in Shanghai Children's Medical Center due to postoperative residual pulmonary artery stenosis from August 2014 to June 2015 were included. The immediate curative effect, follow-up and complications of Pul-Stent implantation were assessed. Comparisons between groups were performed with unpaired Student t test. Results: Pul-Stent implantation of 33 patients (19 males and 14 females) were performed successfully. Thirty-one patients underwent percutaneous stenting, and 2 patients underwent hybrid stenting. A total of 35 Pul-Stents were implanted (19 of model small, 15 of model medium and one of model large), 23 stents were planted in the proximal left pulmonary artery and 12 stents were in the proximal right pulmonary artery. The initial diameter of dilation balloon ranged from 6 to 16 mm, and the long sheath of percutaneous implantation ranged from 8 to 10 F in 29 patients (29/31, 94%). After stenting, the diameter of the narrowest segment of pulmonary artery increased from (4.0±1.7) mm to (9.1±2.1) mm in all patients (t=-21.60, P<0.001). The pressure gradient at the stenosis in 26 patients after biventricular correction decreased from (30.5±12.3) mmHg (1 mmHg=0.133 kPa) to (9.9±9.6) mmHg (t=12.92, P<0.001), and the right ventricular to aortic pressure ratio decreased from 0.57±0.14 to 0.44±0.12 (t=7.44, P<0.001). The pressure of the superior vena cava after stenting in 5 patients after cavopulmonary anastomosis decreased from (17.0±1.9) mmHg to (14.0±0.7) mmHg (t=2.86, P=0.046). Two patients died during reoperation for repairing other cardiac malformations. The remaining 31 patients were clinically stable during the follow-up period of (5.3±1.6) years, and one stent fracture was found on chest X-ray. Cardiac catheterization reexaminations in 16 patients showed that restenosis was found in one stent, while stent position and patency were satisfactory in the remaining stents. Nine children underwent post-dilation without stent fracture, displacement or aneurysm formation. Cardiac tomography showed no stent stenosis, fracture observed, or significant change in diameter of the stent in 8 patients. The inner diameter and pulmonary blood perfusion could not be accurately evaluated due to artifacts by cardiac magnetic resonance imaging in 4 patients. Conclusions: Pul-Stent has good compliance and adequate radial strength, and can dilate further over time to accommodate for somatic growth. It performs safely and effectively in treating post-operative branch pulmonary artery stenosis in children.
Child ; China ; Female ; Follow-Up Studies ; Heart Defects, Congenital/surgery* ; Humans ; Male ; Pulmonary Artery/surgery* ; Retrospective Studies ; Stenosis, Pulmonary Artery/surgery* ; Stents ; Treatment Outcome ; Vena Cava, Superior

OBJECTIVE: To study the value of airway pH monitoring in determining the association between chronic cough and laryngopharyngeal reflux (LPR) in children. METHODS: A total of 274 children with chronic cough who were treated from January 2016 to December 2019 were enrolled. The DX-pH detection system was used to conduct 24-hour airway pH monitoring. The association between chronic cough and LPR was analyzed. RESULTS: Among the 274 children, there were 168 boys and 106 girls, with a median age of 62.8 months and a median airway pH value of 7.3. Of all the 274 children, 99 (36.1%) had LPR, and the incidence rate of LPR was 36.9% (62/168) in boys and 34.9% (37/106) in girls ( CONCLUSIONS LPR is highly associated with the development of chronic cough, and airway pH monitoring may be a safe and effective method for the diagnosis of LPR.
Child ; Child, Preschool ; Chronic Disease ; Cough/etiology* ; Esophageal pH Monitoring ; Female ; Humans ; Hydrogen-Ion Concentration ; Laryngopharyngeal Reflux ; Male

Objective:To analysis the impact of public health emergencies on mood fluctuations of depression and the related factors in the elderly in Shanghai, in order to provide a new evidence for early psychological intervention.Methods:A cross-sectional survey was conducted among 983 elderly in the Department of Geriatrics of Xinhua Hospital Affiliated to Shanghai Jiaotong University and two communities in Changning and Hongkou Districts of Shanghai by using a self-compiled social life questionnaire and Geriatric Depression Scale(GDS-30)during corona virus disease(COVID)-19 outbreak from 1 February to 15 February 2020.The mood fluctuations of depression and the related influencing factors were analyzed by comparing the current GDS-30 scores with the scores within previous six months.Results:Of 983 questionnaires, 867 were valid.The incidence of mild fluctuations of depression was increased from 20.9%(181/867)to 27.2%(235/867)during the public health emergencies( P<0.05), with 3 cases of newly emerged severe depression.The GDS-30 scores were higher during the public health emergencies than before the emergencies(9.88±3.85 vs.7.67±3.54, P<0.05). The four risk factors inducing fluctuations of depression in the elderly were the number of coexisted chronic diseases ≥2( P=0.036), the lack of visits or communication from families( P=0.015), the family members exposing a risk to COVID-19( P<0.01), and the daily viewing of epidemic news more than 4 h( P=0.023). Linear regression analysis showed that cough, sore throat, dizziness, sleep disturbance and dyspnea were significantly related to the aggravation of depression(based on the increase of GDS-30 score)( P<0.05). Conclusions:Public health emergencies may exacerbate depression in the elderly.They are more likely to experience the aggravation of depression when they suffer from multiple chronic diseases, lack the child visits or communications, have the family members exposing a risk to COVID-19 and pay excessive attention to the epidemic.

Objective:To compare and explore the characteristics of striatum functional connectivity in major depression and schizophrenic.Methods:Thirty-six patients with major depressive disorder (MDD), schizophrenia, and health controls were recruited in this study. All subjects underwent rest-stating functional magnetic resonance imaging (rs-fMRI). Routine preprocessing of rs-fMRI data was performed. The regional homogeneity (ReHo), and fractional amplitude of low frequency fluctuation (fALFF) values of the three groups were calculated, separately. Based on the results of one-way analysis of covariance, different brain areas were superimposed to obtain the overlapping regions (the left striatum). Next, the superimposed brain region (the left striatum) was used as the region of interest (ROI), and the customized ROI method was used for the whole-brain functional connectivity analysis. Finally, Pearson correlation analysis was performed between the functional connectivity of the brain regions and clinical features of MDD and schizophrenia.Result:Among the three groups, left striatum extending to the insula and Rolland′s insula showed significant differences of the ReHo values ( P<0.001, AlphaSim correction, voxel number >99);while left superior parietal areas and bilateral insula extending to lentiform nucleus showed significant differences of fALFF values (AlphaSim correction, P<0.001, voxel number >90). The left striatum were superimposed and revealed significant ReHo and fALFF values. The ROI analysis showed that the brain area with different functional connections in the three groups was left inferior temporal gyrus (AlphaSim correction, P<0.001, volume element number>42). The pairwise comparative analysis showed that compared with healthy controls (0.24±0.03), patients with MDD (0.15±0.02) and schizophrenia (0.09±0.01) showed decreased functional connections between the left striatum and the inferior temporal gyrus, and the decline was more significant in patients with schizophrenia. The functional connectivity value of left inferior temporal gyrus was not correlated with HAMD score in MDD( r=-0.02, P=0.93). The functional connectivity value of left inferior temporal gyrus was positively correlated with PANSS positive score in patients with schizophrenia ( r=-0.40, P=0.02). Conclusion:Both MDD and schizophrenia patients may have abnormal function connections of the striatum and the abnormal function connection with the left temporal inferior gyrus may closely related to clinical symptoms of schizophrenia. The brain function activity of striatum and its abnormal connection with the left temporal inferior gyrus may play an important role in the neuropathology of schizophrenia and MDD.

Objective:To compare and explore the characteristics of striatum functional connectivity in major depression and schizophrenic.Methods:Thirty-six patients with major depressive disorder (MDD), schizophrenia, and health controls were recruited in this study. All subjects underwent rest-stating functional magnetic resonance imaging (rs-fMRI). Routine preprocessing of rs-fMRI data was performed. The regional homogeneity (ReHo), and fractional amplitude of low frequency fluctuation (fALFF) values of the three groups were calculated, separately. Based on the results of one-way analysis of covariance, different brain areas were superimposed to obtain the overlapping regions (the left striatum). Next, the superimposed brain region (the left striatum) was used as the region of interest (ROI), and the customized ROI method was used for the whole-brain functional connectivity analysis. Finally, Pearson correlation analysis was performed between the functional connectivity of the brain regions and clinical features of MDD and schizophrenia.Result:Among the three groups, left striatum extending to the insula and Rolland′s insula showed significant differences of the ReHo values ( P<0.001, AlphaSim correction, voxel number >99);while left superior parietal areas and bilateral insula extending to lentiform nucleus showed significant differences of fALFF values (AlphaSim correction, P<0.001, voxel number >90). The left striatum were superimposed and revealed significant ReHo and fALFF values. The ROI analysis showed that the brain area with different functional connections in the three groups was left inferior temporal gyrus (AlphaSim correction, P<0.001, volume element number>42). The pairwise comparative analysis showed that compared with healthy controls (0.24±0.03), patients with MDD (0.15±0.02) and schizophrenia (0.09±0.01) showed decreased functional connections between the left striatum and the inferior temporal gyrus, and the decline was more significant in patients with schizophrenia. The functional connectivity value of left inferior temporal gyrus was not correlated with HAMD score in MDD( r=-0.02, P=0.93). The functional connectivity value of left inferior temporal gyrus was positively correlated with PANSS positive score in patients with schizophrenia ( r=-0.40, P=0.02). Conclusion:Both MDD and schizophrenia patients may have abnormal function connections of the striatum and the abnormal function connection with the left temporal inferior gyrus may closely related to clinical symptoms of schizophrenia. The brain function activity of striatum and its abnormal connection with the left temporal inferior gyrus may play an important role in the neuropathology of schizophrenia and MDD.

Objective:To compare the characteristics and correlation of brain activity and cognitive function between depression and schizophrenia.Methods:36 normal controls (NC), major depression disorder (MDD) and schizophrenia (SZ) patients participated in this study. Digital symbol test (DST), digital span test (DSPT), and verbal fluency test (VFT) were performed. All subjects underwent resting-state fMRI. Routine preprocessing of resting-state fMRI data was performed. The regional homogeneity (ReHo) and fractional amplitude of low frequency fluctuation(fALFF) values were calculated. Cognitive function assessment and brain functional activity characteristics were compared among the three groups. Pearson correlation was used to analyze the correlation between cognitive impairment and brain functional activity.Results:(1) Compared with NC （68.75±10.40, 9.22±1.07, 5.95±1.67, 22.39±4.53）, DST, DSPT and VFT scores decreased in MDD (60.86±10.75, 8.06±0.80, 5.19±1.12, 19.36±2.85） and SZ (46.64±9.50, 7.50±0.91, 4.08±1.05, 14.86±3.78).The decline was more significant in the schizophrenia group （ F=2.39, 1.43, 1.52, 2.16, P<0.01）. (2) Significant differences of the ReHo values in the three groups were all in the left lentiform nucleus-insula-Roland′s island ( F=22.1, P<0.001, AlphaSim correction, voxel number>99), with higher ReHo value in MDD, while lower in SZ. Significant differences of fALFF value in the three groups were in the left superior parietal areas and bilateral insula-lentiform nucleus ( F=28.46, 13.12, P<0.001, AlphaSim correction, voxel number>90). Compared with MDD and NC, SZ showed higher fALFF value in the left superior parietal areas and the bilateral insula-lentiform nucleus （ P<0.05）.(3) The results of correlation analysis showed that DST score of MDD was negatively correlated with ReHo value in the left lentil-insula region ( r=-0.38, P=0.02). DSPT score was negatively correlated with fALFF value in insula-lentiform nucleus in SC ( r=-0.39, P=0.02). Conclusion:The cognitive impairment of schizophrenia is more serious than that of depression; Abnormal activity of parietal lobe, insula and striatum can be prominent in both depressive and schizophrenias patients, and the three brain regions might be the key locations that distinguish schizophrenia from depression in terms of the cognitive impairment.

Objective:To compare the characteristics and correlation of brain activity and cognitive function between depression and schizophrenia.Methods:36 normal controls (NC), major depression disorder (MDD) and schizophrenia (SZ) patients participated in this study. Digital symbol test (DST), digital span test (DSPT), and verbal fluency test (VFT) were performed. All subjects underwent resting-state fMRI. Routine preprocessing of resting-state fMRI data was performed. The regional homogeneity (ReHo) and fractional amplitude of low frequency fluctuation(fALFF) values were calculated. Cognitive function assessment and brain functional activity characteristics were compared among the three groups. Pearson correlation was used to analyze the correlation between cognitive impairment and brain functional activity.Results:(1) Compared with NC （68.75±10.40, 9.22±1.07, 5.95±1.67, 22.39±4.53）, DST, DSPT and VFT scores decreased in MDD (60.86±10.75, 8.06±0.80, 5.19±1.12, 19.36±2.85） and SZ (46.64±9.50, 7.50±0.91, 4.08±1.05, 14.86±3.78).The decline was more significant in the schizophrenia group （ F=2.39, 1.43, 1.52, 2.16, P<0.01）. (2) Significant differences of the ReHo values in the three groups were all in the left lentiform nucleus-insula-Roland′s island ( F=22.1, P<0.001, AlphaSim correction, voxel number>99), with higher ReHo value in MDD, while lower in SZ. Significant differences of fALFF value in the three groups were in the left superior parietal areas and bilateral insula-lentiform nucleus ( F=28.46, 13.12, P<0.001, AlphaSim correction, voxel number>90). Compared with MDD and NC, SZ showed higher fALFF value in the left superior parietal areas and the bilateral insula-lentiform nucleus （ P<0.05）.(3) The results of correlation analysis showed that DST score of MDD was negatively correlated with ReHo value in the left lentil-insula region ( r=-0.38, P=0.02). DSPT score was negatively correlated with fALFF value in insula-lentiform nucleus in SC ( r=-0.39, P=0.02). Conclusion:The cognitive impairment of schizophrenia is more serious than that of depression; Abnormal activity of parietal lobe, insula and striatum can be prominent in both depressive and schizophrenias patients, and the three brain regions might be the key locations that distinguish schizophrenia from depression in terms of the cognitive impairment.