Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Objective:To investigate the application effect of situational simulation combined with the Debriefing-GAS method in the teaching of prenatal genetic counseling.Methods:A total of 30 medical students of the five- and eight-year programs in the classes of 2017 and 2018 who received genetic counseling training in The First Affiliated Hospital of Sun Yat-sen University from May 2021 to May 2022 were selected as research subjects, and situational simulation combined with the debriefing-GAS method was used for the teaching of prenatal genetic counseling. Assessment was performed by the teacher to evaluate the change in genetic counseling abilities during the teaching process, and a questionnaire survey was conducted to investigate the degree of satisfaction with teaching among the students. SPSS 26.0 software was used for data analysis; normally distributed continuous data were expressed as mean±standard deviation, non-normally distributed continuous data were expressed as M d(P 25,P75), and categorical data were expressed as frequency and rate; the paired samples t-test was used for comparison of assessment scores before and after teaching. Results:After teaching, there were significant increases in the assessment scores of genetic counseling [(74.5±18.6) points vs. (87.2±14.5) points, t=4.10, P<0.001] and comprehensive abilities such as clinical ability [(35.4±9.6) points vs. (41.1±6.9) points, t=3.72, P=0.001], doctor-patient communication [(17.5±4.6) points vs. (20.8±3.8) points, t=4.34, P<0.001], professional literacy [(11.0±2.5) points vs. (12.5±2.3) points, t=2.89, P=0.007], teamwork [(3.5±1.0) points vs. (4.2±0.8) points, t=3.67, P=0.001], and organizational effectiveness [(7.1±2.0) points vs. (8.3±1.7) points, t=2.94, P=0.006]. The questionnaire survey showed that the degree of satisfaction among students was rated above satisfaction for the reasonability of the implementation process and links of genetic counseling teaching [3.0 (3.0, 4.0) points], teaching quality [3.5 (3.0, 4.0) points], whether the teaching model could effectively increase the interest and initiative in learning [4.0 (3.0, 4.0) points], the improvement in theoretical knowledge [4.0 (3.0, 4.0) points], communication skills in genetic counseling [3.0 (3.0, 4.0) points], and the understanding of related techniques and application prospect [3.0 (3.0, 4.0) points]. However, two students (6.7%) thought that this teaching model could not efficiently reach teaching objectives, since the teaching process was slightly complicated. Conclusions:Situational simulation combined with the debriefing-GAS method has achieved a good effect in the teaching of prenatal genetic counseling and can help undergraduates to master the theoretical knowledge of prenatal genetic counseling and improve their comprehensive clinical abilities, with a relatively high degree of satisfaction, and therefore, it holds promise for clinical application.

Objective:To develop an imaging-assisted diagnostic tool for schizophrenia based on multimodal magnetic resonance imaging and artificial intelligence techniques.Methods:Three independent datasets were utilized. For each subject, four brain structural metrics including grey matter volume (GMV), white matter volume (WMV), cortical thickness (CT) and deformation-based morphometry (DBM) indicators were extracted from the structural magnetic resonance imaging (sMRI) data, and three brain functional metrics including amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were extracted from the functional magnetic resonance imaging (fMRI) data. To distinguish patients with schizophrenia and healthy controls, single-metric classification models and multi-metrics-fusion classification models were trained and tested using a within-dataset and a between-dataset cross-validation strategy.Results:The results of within-dataset cross-validation showed that the highest accuracy of the single-metric classifications for schizophrenia diagnosis was 86.18% (FC), while the multi-metric-fusion classifications could reach an accuracy of 90.21%. The results of between-datasets cross-validation showed that the highest accuracy of the single-metric classifications for schizophrenia diagnosis was 69.02% (ReHo), while the multi-metric-fusion classifications could reach an accuracy of 71.25%.Conclusion:The functional metrics generally outperforms the structural metrics for the classification between patients with schizophrenia and heathy controls. Additionally, fusion of multi-modal brain imaging metrics can improve the classification performance. Specifically, the fusion of CT, DBM, WMV, FC and ReHo demonstrates the highest classification accuracy, which is a potential tool for imaging-assisted diagnosis of schizophrenia.

Objective:To systematically evaluate the qualitative studies on the decision dilemma of blood glucose management during pregnancy in patients with gestational diabetes mellitus, so as to provide reference for the subsequent formulation of intervention strategies.Methods:The qualitative studies on the decision dilemma of blood glucose management during pregnancy in patients with gestational diabetes mellitus in the Cochrane Library, CINAHL, EMbase, PubMed, PsycINFO, ProQuest, Web of Science, China National Knowledge Internet, Wanfang, VIP and Chinese Biomedical Database were searched from inception to May 2022. The JBI Critical Appraisal Tool for qualitative studies in Australia (2016) was used to evaluate the literature quality, and research results were summarized and integrated by integrating methods.Results:A total of 13 studies were included, 56 themes were extracted, and they were summarized into 9 categories, forming 3 integrated results as following, lack of personalized and professional information on blood glucose management, worring about the influence of blood glucose management on the health of mothers and children, conflict between daily life and blood glucose management plan.Conclusions:Health care workers should provide gestational diabetes mellitus patients with adequate personalized professional information support on blood glucose management to facilitate scientific decision-making during pregnancy, and also analyze the benefits and risks of different decisions for patients to help them make the best decision and strengthen their external support system to help them implement blood glucose management decisions.

Objective:To investigate the role of heparin-binding protein (HBP) as a predictor of early bacterial infections in patients with traumatic intracerebral hemorrhage.Methods:Patients with traumatic intracerebral hemorrhage admitted to the Emergency Department of the First Hospital of Shanxi Medical University from September 2021 to June 2022 were collected prospectively. Patients with bacterial infection diagnosed by pathogenic examination were classified as the infected group, and those with negative pathogenic examination were classified as the non-infected group. Peripheral blood HBP counts were measured within 48 h of admission, and general information and relevant laboratory tests were collected. The differences of the indicators between the two groups were compared, the receiver operating characteristic (ROC) curve was drawn, the predictive value of the indicators for patients with co-infection was assessed, and the valuable predictors were screened out using multivariate logistic regression analysis.Results:Eighty-five patients [44 males and 41 females, aged (55.09±1.18) years] , were included in the study. Among the patients included in the study, 39 patients had bacterial infection and 46 were non-infected. Patients in the infected group were older , and had more surgeries, higher respiratory rate and injury severity score, and higher levels of HBP [(33.00±3.49) ng/mL vs. (16.27±1.61) ng/mL, P<0.001], leukocytes, and neutrophils [(15.32±3.19) ×10 9/L vs. (6.69±0.57) ×10 9/L, P=0.005] than in the non-infected group, while the Glasgow Coma Scale [(8.72±0.63) vs. (11.37±0.48), P=0.001] was lower than that in the non-infected group, with statistically significant differences (all P<0.05). There was no significant differences in lymphocytes, red blood cells, platelets, calcium, procalcitonin and coagulation indexes between the two groups (all P>0.05). Logistic regression analysis showed that neutrophils ( OR=1.252, 95% CI: 1.075-1.457, P=0.004) and HBP ( OR=1.081, 95% CI: 1.025-1.141, P=0.004) were independent risk factors for infection in patients with traumatic cerebral hemorrhage. The area under ROC curve for HBP of diagnosing early co-infection in patients with traumatic intracerebral hemorrhage was 0.82 (95% CI: 0.71-0.88), the sensitivity was 92.31%, and the specificity was 52.17%. Conclusions:HBP is a valuable predictor of early traumatic intracerebral hemorrhage complicated with bacterial infection in the emergency department, and has a good supplementary value to the existing test indicators.

Objective:To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases.Methods:From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) .Results:① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups ( P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups ( P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively ( P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % ( P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion:The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.

Objective:To evaluate the clinical value of percutaneous transhepatic one-step biliary fistulation(PTOBF)lithotomy plus laparoscopic cholecystectomy(LC) in the treatment of choledocholithiasis combined with cholecystolithiasis.Methods:From Jul 2012 to Jun 2018, 44 patients with cholecystolithiasis and choledocholithiasis were treated by PTOBF + LC ( n=20) vs laparoscopic common bile duct exploration(LCBDE)+ LC( n=24). Results:The success rate of one-step operation in both groups was 100%.The average intra-operative hemorrhage and the average hospital stay after operation were higher in LCBDE+ LC group (all P<0.05). The post-operative complication rate of PTOBF lithotomy + LC group was 10.0% (2/20), recurrence rate of observation period was 10.0% (2/20), while that of LCBDE+ LC group was 8.3% (2/24), and 12.5% (3/24), the difference was not statistically significant (all P>0.05). Conclusion:PTOBF lithotomy combined with LC is a safe, effective and feasible minimally invasive method for the treatment of choledocholithiasis combined with gall stones.

Objective To investigate the outcomes of fetuses with hemolytic anemia caused by red cell alloimmunization following intrauterine transfusion (IUT),and to analyze the influence of hydrops fetalis on IUT treatment.Methods A retrospective analysis was conducted on 70 fetuses,who were admitted to the Fetal Medicine Center,the First Affiliated Hospital of Sun Yat-sen University from January 2005 to May 2018,with hemolytic disease requiring IUT.Clinical data of the fetuses and the gravidas were collected and divided into hydrops group (17 cases) and non-hydrops group (53 cases) based on their conditions before IUT.Results of routine blood tests before and after the first IUT,gestational age at the first IUT,prognosis and outcomes of the fetuses were compared between two groups.t-test,rank-sum test,Chi-square test (or Fisher's exact test) and multivariant logistic regression analysis were used for data analysis.Results Totally,the 70 fetuses underwent 231 times of IUT.Compared with the non-hydrops group,the hydrops group had a significantly increased incidence of severe anemia [14/17 vs 47.2％ (25/53),x2=6.458,P=0.011],but decreased hemoglobin [(38.5 ± 21.4) vs (68.7± 19.3) g/L,t=5.471,P＜0.001] and hematocrit level [0.110 (0.044-0.246) vs 0.222 (0.077-0.299),Z=-4.390,P＜0.001] before the first IUT.After the IUT,the survival rate of the fetuses in hydrops group was significantly lower than that of the non-hydrops group [11/15 vs 94.3％ (50/53),P=0.038].There was no significant difference in gestational age at birth,birth weight,neonatal hemoglobin level at birth,the incidence of exchange transfusion,the number of blood transfusions required or the incidence of severe neonatal complication between the two groups (all P＞0.05).Logistic regression analysis indicated that the fetal hydrops was an independent risk factor for fetal survival (OR=12.8,95％CI:1.2-136.4,P=0.035).Conclusions Hydrops fetalis might reduce the survival rate of fetal hemolytic disease after 1UT.

Objective: To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) . Methods: Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression. Results: The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ²=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ²=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) . Conclusion High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.