Omics Analysis of Ferroptosis and Establishment of Prognostic Model for multiple myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients.@*METHODS@#Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM.@*RESULTS@#36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients.@*CONCLUSION@#Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.

Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes / 中国实验血液学杂志

OBJECTIVE@#To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes.@*METHODS@#The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score.@*RESULTS@#A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect.@*CONCLUSION@#Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.

Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients. @*Materials and Methods@#A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored. @*Results@#TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion. @*Conclusion@#This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.

Quantitative evaluation of right atrial function in fetuses with moderate to severe tricuspid regurgitation by two-dimensional speckle tracking echocardiography / 中华超声影像学杂志

Objective:To explore the application value of two-dimensional speckle tracking echocardiography (2D-STE) in measuring the global longitudinal peak strain of the right atrium (PRAGLS) in normal fetuses and evaluating PRAGLS in assessing right atrial function in fetuses with moderate and severe tricuspid regurgitation (TR).Methods:A total of 25 fetuses diagnosed with moderate and severe TR, who underwent fetal echocardiography at Run Run Shaw Hospital, Zhejiang University College of Medicine between October 2020 and May 2022, were selected as the case group. Their gestational age ranged from 25.00(24.00, 30.00)weeks. Additionally, 100 normal singleton fetuses were chosen as the control group, with a gestational age of 25.83(23.00, 28.75)weeks. Standard basal or apical four-chamber clips were acquired and inputted into TOMTEC-ARENA offline cardiac analysis software for analysis. The fetal PRAGLS values of the two groups were obtained, as well as the routine obstetric ultrasound measurements and fetal echocardiographic parameters of both groups: fetal heart rate (FHR), biparietal diameter (BPD), femur length (FL), aortic annulus inner diameter (AO), pulmonary annulus inner diameter (PA), PA/AO ratio, right atrial end-systolic length (RAESL), right atrial end-systolic diameter (RAESD), right atrial end-systolic area (RAESA), right ventricular end-diastolic diameter (RVEDD), and tricuspid annular plane systolic excursion (TAPSE). The peak TR velocity and pressure gradient were simultaneously measured in the case group.The differences in fetal PRAGLS and other parameters between the two groups were compared and analyzed. The correlation between fetal PRAGLS and gestational age (GA) and routine measurements was assessed for both groups. Intra- and inter-observer repeatability tests were conducted using the intragroup correlation coefficient (ICC).Results:A significant difference in PRAGLS was observed between the two groups ( t=11.55, P<0.01). The TAPSE difference between the two groups was also statistically significant ( Z=3.45, P=0.01). Notable differences were found in AO, PA, PA/AO, RAESL, RAESD, and RAESA between the two groups (all P<0.05), but no significant differences were identified in age, GA, FHR, BPD, FL, and RVEDD between the two groups (all P>0.05). PRAGLS in the control group exhibited a moderate negative correlation with GA ( r=-0.47, P<0.01) and were correlated with BPD, FL, AO, PA, RAESL, RAESD, RAESA, and RVEDD ( r=-0.50, -0.46, -0.39, -0.43, -0.45, -0.36, -0.43, -0.32, all P<0.05). No significant correlation was observed with maternal age, FHR, PA/AO, and TAPSE (all P>0.05). No significant correlation between PRAGLS and GA or other conventional parameters was found in the case group (all P>0.05). The inter-measurer and intra-measurer ICC of PRAGLS in the control group were 0.87 and 0.79, respectively, while the inter-measurer and intra-measurer ICC of PRAGLS in the case group were 0.94 and 0.97, respectively, demonstrating good consistency. Conclusions:2D-STE exhibits strong feasibility and reproducibility in assessing fetal atrial function.Fetuses with moderate and severe TR display decreased PRAGLS, suggesting impaired right atrial reservoir function. Right atrial strain introduces a novel method for evaluating fetal cardiac function.

Preliminary study of cardiac morphology and function in fetuses with tetralogy of Fallot using fetal heart quantification / 中华超声影像学杂志

Objective:To evaluate the fetal heart shape and function in tetralogy of Fallot (TOF) by fetal heart quantitative analysis (fetal HQ).Methods:A total of 52 fetuses with TOF diagnosed by fetal echocardiography and 200 normal fetuses matched with their gestational weeks from March 2020 to March 2022 at Sir Run Run Shaw Hospital, Zhejiang University were retrospectively evaluated. The basic parameters of fetal cardiac blood vessels in the two groups were measured by fetal HQ technology and conventional M-mode ultrasound technology: aortic valve diameter(AV), pulmonary artery valve diameter(PV), main pulmonary artery diameter (MPA) and Z-score. The overall morphometric measurements including end-diastolic length diameter, transverse diameter, area, and global spherical index (GSI) of the fetal heart in the 4-chamber view(4CV), area and length of the right and left ventricles and their ratios. Measurements of left and right ventricular function included ejection fraction (EF), fraction area change rate (FAC), tricuspid annular plane systolic excursion (TAPSE), left and right ventricular global longitudinal strain (GLS), and left and right ventricular end-diastolic diameter (ED), spherical index (SI), and fractional shortening rate (FS) of 24-segments. The differences of above parameters between TOF group and control group were compared. In addition, the relationships between the absolute value of left and right ventricular GLS of TOF fetus and PV/AV, PV Z-score and MPA Z-score were analyzed. The optimal critical values of GSI, left ventricular EF and left ventricular FAC of TOF fetus were determined by ROC curve, and their corresponding sensitivity and specificity were obtained.Results:Compared with control group, there were significant differences in 4CV end-diastolic length, area, GSI, left ventricular area, left ventricular length, left ventricular EF, left ventricular FAC and left ventricular GLS in TOF group (all P<0.05). There were significant differences in ED between left ventricular 15-24 segments and right ventricular 1-21 segments (all P<0.05). There were significant differences in SI between left ventricular 1-16 segments, 21-24 segments and all segments of right ventricle (all P<0.05). The differences in FS were statistically significant (all P<0.05) when comparing all segments of the left ventricle and 1-2 segments of the right ventricular, and the remaining parameters were not statistically significant (all P>0.05). The left ventricular GLS absolute value of TOF fetuses was positively correlated with PV/AV, PV Z-score and MPA Z-score( rs=0.338, 0.441 and 0.458, all P<0.05), the right ventricular GLS absolute value of TOF fetuses was positively correlated with PV AV, PV Z-score and MPA Z-score( rs=0.418, 0.368 and 0.338, all P<0.05). The optimal critical values of GSI, left ventricular EF, and left ventricular FAC in the diagnosis of fetal TOF were 1.19, 59.05%, and 44.4%, respectively. At this time, the sensitivities of diagnosis of TOF were 0.78, 0.75, and 0.80, respectively. The specificities were 0.88, 0.88 and 0.83, respectively. The areas under ROC curve were 0.89, 0.88 and 0.89, respectively. Conclusions:Fetal HQ technology can provide a simple and reliable quantitative evaluation of fetal heart shape and function, and provide certain theoretical parameters for the study of fetal heart shape and function.

Investigation of fetal cardiac size, morphology and function in fetuses with right ventricular outflow obstruction using fetal heart quantification / 中华超声影像学杂志

Objective:To investigate the application value of fetal heart quantification (fetal HQ) in the evaluation of fetal heart size, morphology and function in fetuses with right ventricular outflow obstruction (RVOTO).Methods:Fifty-five fetuses diagnosed as RVOTO by fetal echocardiography in Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University from April 2020 to February 2021 were selected. They were divided into simple pulmonary artery stenosis (PS) group and conus arteriosus malformation (CTD) group according to whether they were combined with other cardiovascular malformations. On the standard four chamber view, the end diastolic basal apical length (4CV length) and transverse width (4CV width) were obtained by fetal HQ analysis technique, and the cardiac global spherical index (4cv-gsi) was calculated. The left and right ventricles (LV and RV) were divided into 24 segments from the base to the apex. The endocardial curve was obtained by total HQ tracking. The 24 segment transverse width (ED), spherical index (SI), short axis shortening (FS) and its Z-score were calculated. The LV and RV of RVOTO fetuses were compared and analyzed from the aspects of heart size, morphology and function.Results:The 4CV length of RVOTO fetal heart was in the normal range, 4CV width increased in varying degrees, GSI decreased, and the whole heart showed spherical changes. In PS group, LV-ED was larger than that of RV and the difference was statistically significant in 5-24 segments( P<0.05). LV was more spherical than RV. There was no significant difference in ED between LV and RV in CTD group( P>0.05), and RV was more spherical than LV. Twenty-four segment FS decreased in different degrees in RVOTO fetal heart, and the decrease of RV was more obvious than that of LV. There was significant difference between the LV and RV in PS group from S5 to 19 ( P<0.05), and there was significant difference between the left and right ventricles in CTD group from S1 to 11 ( P<0.05). Conclusions:Fetal HQ can provide new insights of cardiac size, morphology and function in fetuses with RVOTO.

Study on establishing the reference range of atrial septal excursion index and foramen ovale membrane angle in normal fetuses aged 16-40 weeks / 中华超声影像学杂志

Objective:To establish the normal reference range of atrial septal excursion index (ASEI) and foramen ovale membrane angle in normal fetuses aged 16-40 weeks, and to analyze the correlation between ASEI and foramen ovale membrane angle in normal fetuses.Methods:A total of 378 normal singletons with gestational ages of 16-40 weeks undergoing by fetal echocardiography were selected in the Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, from January to June 2021, and 349 fetuses successfully finished all measurements. After all fetuses completed the systematic fetal echocardiography, fetal foramen ovale diameter and foramen ovale membrane angle were measured on the four chamber view. The maximum distance of foramen ovale valve from the base of atrial septum to the free wall of left atrium and the transverse diameter of left atrium were measured, and ASEI was calculated. The differences of ASEI, foramen ovale membrane angle and foramen ovale diameter of the groups with different gestational weeks were compared. The correlations among ASEI, foramen ovale membrane angle and foramen ovale diameter were analyzed by Pearson correlation analysis.Results:All 349 fetuses were divided into 6 groups according to their gestational weeks, including 17 cases at 16-20 weeks, 46 cases at 21-24 weeks, 114 cases at 25-28 weeks, 105 cases at 29-32 weeks, 31 cases at 33-36 weeks and 36 cases at 37-40 weeks. The ± s of ASEI was 0.492 7±0.059 7, 95% CI was 0.486 4-0.499 0, 95% normal reference value range was 0.375 7-0.609 8. Significant differences were found in ASEI among different groups( P<0.05). The ± s of foramen ovale membrane angle was (44.03±5.48)°, 95% CI was 43.46-44.61°, 95% normal reference value range was 33.29-54.78°. Significant differences were found in the foramen ovale membrane angle among different groups( P<0.05). The ± s of foramen ovale diameter was (4.32±1.30)mm, 95% CI was 4.18-4.45 mm, the differences among different groups were significant( P<0.05) and foramen ovale diameter was found increased with the increase of gestational weeks. There was a significant positive correlation between ASEI and foramen ovale membrane angle ( r=0.558, P<0.05). There was no correlation between foramen ovale diameter and ASEI and foramen ovale membrane angle ( r=-0.166, -0.084; all P>0.05). Conclusions:The normal reference ranges of ASEI and foramen ovale valve angle of normal fetuses aged 16-40 weeks was successfully established. These parameters may be useful for evaluating diastolic cardiac function by assessing foramen ovale.

m7G-lncRNAs are potential biomarkers for prognosis and tumor microenvironment in patients with colon cancer / 南方医科大学学报

OBJECTIVE@#To assess the value of m7G-lncRNAs in predicting the prognosis and microenvironment of colorectal cancer (CRC).@*METHODS@#We screened m7G-lncRNAs from TCGA to construct an m7G-lncRNAs risk model using multivariate Cox analysis, which was validated using ROC and C-index curves. Calibration and nomogram were used to predict the prognosis of CRC patients. Point-bar charts and K-M survival curves were used to assess the correlation of risk scores with the patients' clinical staging and prognosis. CIBERSORT and ESTIMATE were used to explore the association between the tumor microenvironment and immune cell infiltration in patients in high and low risk groups and the correlation of risk scores with microsatellite instability, stem cell index and immune checkpoint expression. A protein-protein interaction network was constructed, and the key targets regulated by m7G-lncRNAs were identified and validated in paired samples of CRC and adjacent tissues by immunoblotting.@*RESULTS@#We identified a total of 1722 m7G-lncRNAs from TCGA database, from which 12 lncRNAs were screened to construct the risk model. The AUCs of the risk model for predicting survival outcomes at 1, 3 and 5 years were 0.727, 0.747 and 0.794, respectively. The AUC of the nomogram for predicting prognosis was 0.794, and the predicted results were consistent with actual survival outcomes of the patients. The patients in the high-risk group showed more advanced tumor stages and a greater likelihood of high microsatellite instability than those in the low-risk group (P < 0.05). The tumor stemness index was negatively correlated with the risk score (r=-0.19; P=7.3e-05). Patients in the high-risk group had higher stromal cell scores (P=0.0028) and higher total scores (P=0.007) with lowered expressions of activated mast cells (r=-0.11; P=0.045) and resting CD4+ T cells (r=-0.14; P=0.01) and increased expressions of most immune checkpoints (P < 0.05). ATXN2 (P= 0.006) and G3BP1 (P=0.007) were identified as the key targets regulated by m7G-lncRNAs, and their expressions were both higher in CRC than in adjacent tissues.@*CONCLUSION@#The risk model based on 12 m7G-lncRNAs has important prognostic value for CRC and can reflect the microenvironment and the efficacy of immunotherapy in the patients.

Analysis of Mycobacterium tuberculosis drug susceptibility test results and its spatial distribution characteristics in Dali Bai Autonomous Prefecture from 2017 to 2019 / 中华检验医学杂志

Objective:Analyze the drug resistance of Mycobacterium tuberculosis (MTB) to commonly used anti-tuberculosis drugs and its spatial distribution in Dali Bai Autonomous Prefecture from 2017 to 2019, which would provid a reference for the treatment of tuberculosis and the prevention and control of drug-resistant tuberculosis. Methods:A total of 1 013 Mycobacterial strains were isolated from sputum samples in the tuberculosis laboratories of the designated People′s hospital of 12 counties (cities) of Dali Bai Autonomous Prefecture from January 2017 to December 2019. Proportional method was used to conduct drug susceptibility tests and strain identification of 6 anti-tuberculosis drugs. Further used ArcMap10.2 and GeoDa1.14 software to visualize the map display and spatial autocorrelation analysis of the drug resistance of MTB.Results:From 2017 to 2019, the drug resistance rates of MTB in Dali Prefecture were 10.33%(28/271), 10.35%(55/531) and 30.00%(51/170), respectively, showing an rising trend ( χ2=26.62, P<0.05). Among 1 030 samples, 972 strains (95.95%) was MTB and 41 strains (4.05%) was non-tuberculous Mycobacterium (NTM). The total resistance rate of 972 strains of MTB was 13.79% (134/972), of which the single resistance rate was 6.59% (64/972), the multi-drug resistance rate was 4.84% (47/972), and the poly-drug resistance rate was 2.06% (20/972), the rate of extensive drug resistance is 0.31% (3/972). There are 25 combinations of drug resistance patterns. The detection rate of NTM was 4% (41/1 013), among which Midu County had the highest detection rate (0.89%, 9/1 013). The spatial distribution showed that the number of MTB resistant strains among counties and cities had a negative spatial correlation (Moran′s I value was -0.367, P<0.05). It shows that there is no clustering of drug resistance among counties and cities, and the resistance is serious in individual counties and cities. Yongping County and Nanjian Yi Autonomous County had low and high aggregation, and Yunlong County had high and low aggregation. Conclusions:The drug resistance of MTB showed an rising trend in Dali Bai Autonomous Prefecture from 2017 to 2019. The number of drug-resistant strains among regions was not randomly distributed, the regional difference was large, and spatial autocorrelation analysis provided theoretical clues and basis for the formulation of drug resistance prevention and control measures for tuberculosis in the whole state.

Investigation of fetal cardiac function and morphology in fetuses with left ventricular outflow tract obstruction using fetal heart quantification / 中华超声影像学杂志

Objective:To explore the application value of fetal heart quantification (fetal HQ) in evaluation of fetal cardiac function and morphology in fetuses with left ventricular outflow tract obstruction (LVOTO).Methods:Twenty-five fetuses with LVOTO diagnosed by fetal echocardiography in Sir Run Run Shaw Hospital, Zhejiang University Medical College from April to July 2020 were enrolled. The end-diastolic basal apical length(BAL), transverse length (TL), global spherical index (GSI) of fetal four-chamber view, and the left and right ventricular end-diastolic area, long diameter, 24-segment end-diastolic transverse length (ED) and its Z-scores adjusted by gestational age and 24-segment spherical index(SI) were calculated by using fetal HQ. Subsequently the Z-scores of left and right ventricle fractional shortening (FS) in 24 segments were obtained by gestational age.Results:SI of 24-segments of left ventricles in fetuses with LVOTO were significantly different from that of right ventricles (all P<0.05). There was significant difference between left and right ventricular areas ( P<0.05). There was no significant difference between left and right ventricular lengths ( P>0.05). There were significant differences between the 24-segment Z-scores of left and right ventricular ED(all P<0.05). The ratios of RVED to LVED of 24 segments were analyzed by box diagram. The results showed that the transverse length of right ventricle was significantly higher than that of left ventricle. The highest value was 1.49(1.26-1.86), and the lowest value was 1.40(1.26-1.86), both significantly higher than the normal value of 1.19. There were no significant differences between the 1-19-segment Z-scores of left and right ventricular FS( P>0.05). There were significant differences between the 20-24-segment Z-scores of left and right ventricular FS( P<0.05). Conclusions:Fetal HQ can be used to quantitatively analyze left ventricular shape, size and function of fetuses with LVOTO, which provides a new method for quantitative analysis of fetal heart function.

Study on the feasibility of automatic quantification of cardiac axis by fetal intelligent navigation echocardiography / 中华超声影像学杂志

Objective:To explore the feasibility of fetal intelligent navigation echocardiography (FINE) in automatic quantitation of cardiac axis (CA).Methods:A total of 62 pregnant women of which 2 with twins′ pregnancy in the second and third trimesters from May to June 2020 in Sir Run Run Shaw Hospital Zhejiang University College of Medicine were enrolled in this non-selective and prospective study. After excluding those who could not be analyzed, they were assigned into four groups according to their CA measuring methods: ①Group with manual measuring CA in systole (CAS); ②Group with manual measuring CA in diastole(CAD); ③Group with CA measured by FINE in three-steps; ④Group with CA measured by FINE in seven-steps. The CAS among groups were compared in order to analyze the consistency and correlation of CAS achieved by different methods, meanwhile, the intra-observer and inter-observer consistency and repeatability were also evaluated.Results:A total of 64 fetuses with 187 volume data were collected, of which 60 cases of fetal data can be included in the study, 57 cases of normal CA, 3 cases of abnormal CA, a total of 158 volume data can be used for data analysis, the success rate was about 84.5%. Because of the small number of abnormal CA cases (3 cases), only 57 cases of normal CA were statistically analyzed in this study. Three-step and seven-step FINE automatic quantitative CA showed significantly different from those obtained with manual measurements of CAD ( P=0.005, P<0.001). There were no significant differences in quantitative analysis of CA between three-step or seven-step FINE and manual measurements of CAS ( P=0.458, 0.883), however, there was no correlation between CA using three-step FINE and manual measurement of CAS ( rs=0.056, P=0.679), but there was a positive correlation between CA using seven-step FINE and manual measurement of CAS ( rs=0.599, P<0.001). The linear regression equation was constructed as follows: Y=10.96+ 0.73 X ( R2=0.431, P<0.001). There was no correlation between three-step method and seven-step method for automatic quantitative CA ( rs=0.158, P=0.241). There was significant difference( P<0.001), but strong correlation between manual measurement of CAS and manual measurement of CAD ( rs=0.973, P<0.001), the average difference was ΔCA=(4.5± 3.8)°. The linear regression equation was constructed as follows: Y=-2.94+ 0.96 X ( R2=0.950, P<0.001). Intra-observer and inter-observer measurements had shown no significant difference in consistency and repeatability (all P>0.05). Conclusions:The measurement of fetal CA by seven-step FINE is superior to the three-step FINE when the fetal CA is in normal range. This may be considered a promising aspect that seven-step FINE automatic quantitation of fetal CA can replace the manual measurement of CAS. Future research is needed to deliminate the reliability of automatic quantification of fetal CA by seven-step FINE with the CA in abnormal range.

Bioinformatics Analysis of the Influence of Coronavirus Infection on Hematopoietic System and Potential Intervention Drugs and Their Significance for COVID-19 / 中国实验血液学杂志

OBJECTIVE@#To analyze and predict the effect of coronavirus infection on hematopoietic system and potential intervention drugs, and explore their significance for coronavirus disease 2019 (COVID-19).@*METHODS@#The gene expression omnibus (GEO) database was used to screen the whole genome expression data related with coronavirus infection. The R language package was used for differential expression analysis and KEGG/GO enrichment analysis. The core genes were screened by PPI network analysis using STRING online analysis website. Then the self-developed apparent precision therapy prediction platform (EpiMed) was used to analyze diseases, drugs and related target genes.@*RESULTS@#A database in accordance with the criteria was found, which was derived from SARS coronavirus. A total of 3606 differential genes were screened, including 2148 expression up-regulated genes and 1458 expression down-regulated genes. GO enrichment mainly related with viral infection, hematopoietic regulation, cell chemotaxis, platelet granule content secretion, immune activation, acute inflammation, etc. KEGG enrichment mainly related with hematopoietic function, coagulation cascade reaction, acute inflammation, immune reaction, etc. Ten core genes such as PTPRC, ICAM1, TIMP1, CXCR5, IL-1B, MYC, CR2, FSTL1, SOX1 and COL3A1 were screened by protein interaction network analysis. Ten drugs with potential intervention effects, including glucocorticoid, TNF-α inhibitor, salvia miltiorrhiza, sirolimus, licorice, red peony, famciclovir, cyclosporine A, houttuynia cordata, fluvastatin, etc. were screened by EpiMed plotform.@*CONCLUSION@#SARS coronavirus infection can affect the hematopoietic system by changing the expression of a series of genes. The potential intervention drugs screened on these grounds are of useful reference significance for the basic and clinical research of COVID-19.

Exploration of Mechanism of Guben Qingyuan Prescription Combined with Androgen Deprivation Therapy Against Castration-resistant Prostate Cancer from AR/AR-V7 Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the efficacy and mechanism of Guben Qingyuan prescription combined with androgen deprivation therapy （ADT） in the treatment of castration-resistant prostate cancer （CRPC）. Method:A CRPC-bearing mouse model was established. When the tumor volume reached about 100 mm³， 50 CRPC-bearing BALB/c nude mice were randomly divided into the model group， ADT group， and ADT+low-， medium-， high-dose Guben Qingyuan prescription groups， with 10 mice in each group. After grouping， it was ensured that there was no statistically significant difference in tumor volume between groups. The mice in the model group was treated with the same amount of normal saline （10 mL·kg^-1） by gavage， twice a day， while those in the other groups were provided with bicalutamide （5 mg·kg^-1） for intragastric administration， once a day， and then with goserelin （0.36 mg·kg^-1） for intraperitoneal injection on the 10th day. On the basis of ADT， the ones in the ADT+Guben Qingyuan prescription groups further received Guben Qingyuan prescription at the low （2.5 g·kg^-1）， medium （25 g·kg^-1）， and high doses （50 g·kg^-1） by gavage， twice a day. After 25 days of continuous administration， the tumor tissue was harvested for recording the tumor growth and calculating the tumor inhibition rate. The mRNA and protein expression levels of androgen receptor （AR）， androgen receptor splice variant-7 （AR-V7）， and prostate-specific antigen （PSA） were detected by real-time polymerase chain reaction （Real-time PCR） and Western blot assay. Result:The tumor inhibition rates of the ADT+low-， medium-， and high-dose Guben Qingyuan prescription groups were 27.95%， 46.71%， and 44.46%， respectively， and the inhibition rates in the ADT+medium- and high-dose Guben Qingyuan prescription groups were significantly increased as compared with that in the ADT group （<italic>P</italic><0.05）. As revealed by comparison with the ADT group， Guben Qingyuan prescription at the medium and high doses significantly down-regulated the mRNA and protein expression levels of AR， AR-V7， and PSA （<italic>P</italic><0.05）. Conclusion:Guben Qingyuan prescription combined with ADT is efficient in controlling the tumor growth in CRPC-bearing mice， which is related to the regulation of AR/AR-V7 signaling pathway.

A preliminary study of 24-segment spherical indexes of fetal ventricles in the middle and late trimestries by automatic fetal heart quantification / 中华超声影像学杂志

Objective:To explore the clinical application value of fetal heart quantification (fetal HQ) in the analysis of 24-segment spherical index (SI) of fetal heart in normal second and third trimestries.Methods:In July 2019, sixty-five normal singletons with gestational age (GA) of 28(24, 31) weeks were examined by echocardiography in Sir Run Run Shaw Hospital. The global spherical index (GSI) of the heart was measured and the dynamic images of the standard four chamber view were collected. Twenty-four-segment SI of the left and right ventricles were measured by using the fetal HQ analysis system and the correlation between SI and gestational age was analyzed.Results:There were no significant correlations between GSI, SI of left and right ventricles and gestational age ( r s=-0.22-0.14, all P>0.05). The SI of the first segment of left ventricle was lower than those of the other 23 segments (all P<0.05). There were no significant differences of SI among the second to the eleventh segments of the left ventricle (all P>0.05). In the 13th to the 24th segments of the left ventricle, the closer to the apex of the heart, the greater the SI of the segment were noted (all P<0.05). For the right ventricle, the closer to the apex of the heart, the greater the SI of the 4th to the 24th segments were found (all P<0.05), and there were no significant differences in SI among the first to third segment( P>0.05). The success rate of fetal HQ software was 95.4%. Conclusions:The 24-segment SI of RV and LV provides a feasible and reliable quantitative method which allows for the assessment of fetal heart function from the four-chamber view.

Quantification of Z-scores of normal fetal left and right ventricular diameters using early fetal echocardiography / 中华超声影像学杂志

Objective:To investigate the association of left and right ventricular diameters in normal early pregnancy and early middle pregnancy to the biological growth parameters of fetus, and to establish the reference and Z-score model for left and right ventricles.Methods:Two hundred and forty-six fetuses in normal early pregnancy (11-13 + 6 weeks) and early middle pregnancy (14-17 + 6 weeks) from February 2019 to May 2019 in Sir Run Run Shaw Hospital were examined by routine ultrasound. Non-cardiac fetal biometric parameters included crown-rump length (CRL), biparietal diameter (BPD) and femoral length (FL) and gestation age (GA) based on menstrual age were assessed. The left and right ventricular widths (LVW, RVW) and ventricular lengths (LVL, RVL) were measured at the end of diastolic period by obtaining the standard four chamber view of fetal echocardiography. The end-diastolic areas (LVA, RVA) as the products of the ventricular widths and lengths, the global spherical indexes (GSI) of left and right ventricles (LVSI, RVSI), the ratios of left and right ventricular widths (LVW/RVW), the length ratios (LVL/RVL) and the area ratios (LVA/RVA) of both ventricles were calculated.GA, BPD and FL were used as independent variables. The predicted cardiac parameters and its derivative parameters were used as dependent variables. The corresponding reference range was established. The correlation between each standard deviation (SD) and independent variables was analyzed, and the corresponding Z-scores of left and right ventricular diameters were calculated by using the formula. Results:①LVW, RVW, LVL, RVL were found positively correlated with the increase of GA, BPD and FL, and the correlation between GA and LVW, RVW was the highest ( r=0.928, 0.930; all P<0.000 1). ②There was a positive correlation between LVA, RVA and GA ( r=0.868, 0.872; all P<0.000 1). LVSI, RVSI were found negatively correlated with GA ( r=-0.844, -0.861; all P<0.000 1), and LVSI>RVSI. LVW/RVW<1 and almost close to 1, the ratios decreased with the increase of GA( r=0.147, P<0.000 1). LVL/RVL>1, the ratios increased with the increase of GA( r=0.313, P<0.000 1). LVA/RVA>1, but there was no correlation with GA. ③The SD values of LVW, RVW, LVL, RVL positively correlated with independent variables. Taking GA and LVW as an example, the linear regression equation of LVW was Y=-5.338+ 0.549GA ( r=0.928, P<0.000 1), and the linear regression equation of LVW-SD was Y=-0.322+ 0.037GA( r=0.131, P<0.000 1). The Z-scores of LVW, RVW, LVL, RVL, LVA, RVA did not change with the changes of GA, BPD, and FL. Conclusions:The normal reference range and Z-scores of left and right ventricular lengths and widths can be simply and reliably established using statistical analysis, and these parameters might have potentials for more accurately and more early evaluating the normal development of fetal heart.

Clinical value of sonography based volume computer aided display heart (SonoVCADheart) in the display of key diagnostic elements in basic fetal echocardiographic views / 中华超声影像学杂志

Objective:To evaluate the clinical value of sonography based volume computer aided display heart (SonoVCADheart) in the display of key diagnostic elements in basic fetal echocardiographic views.Methods:4D volume data based on fetal four-chamber view of 80 singleton fetuses (including 57 normal fetuses and 23 fetuses with heart abnormalities) were collected by using a volumetric probe from the Sir Run Run Shaw Hospital, Zhejiang University College of Medicine from January 8-22, 2019. Four to five volume datasets based on four-chamber view of the heart were rapidly acquired from each fetus. Three doctors (Doctor A: Engaged in fetal echocardiography diagnosis for more than 15 years, Doctor B and C: 6 months of regular fetal echocardiography training but lack of experience) with different fetal echocardiographic experiences performed off-line processing using SonoVCADheart combined tomographic ultrasound imaging (TUI) at different times to obtain eight standard echocardiographic diagnostic views, and to score the elementary contents of each echocardiographic view. The scores of the same doctor at different times, the scores of less experienced doctors and experienced doctor, and the scores between normal and abnormal fetuses, and the time required for analysis and diagnosis among all doctors were analyzed and compared, respectively. The diagnostic coincidence rates of SonoVCADheart for fetuses with cardiac malformations were also assessed.Results:A total of 279 volume datasets obtained from 57 normal fetuses, an average of 4.89/fetus, and 109 volume datasets obtained from 23 fetuses with cardiovascular abnormalities, an average of 4.74/fetus, and all volume datasets were used for SonoVCADheart analysis. The volume percentage of all the elements in the 8 diagnostic views with image quality≥2 points shown by SonoVCADheart in the normal fetuses was about 70.61%-74.91%, in the abnormal fetuses was about 53.21%-55.96%. There were no significant differences in the scores between the same doctor at different times, the scores between inexperienced doctors, and the scores among experienced and less experienced doctors(all P>0.05). There were significant differences in the scores between normal and abnormal fetuses except for all of the superior and inferior vena cava view and the aorticarch view of doctors A and C(all P<0.05). The time required for experienced doctor A and inexperienced doctors B and C to obtain 8 diagnostic views and to complete the diagnosis was statistically significant ( P<0.05). There was no significant difference in the time required for the inexperienced doctors B and C to obtain 8 diagnostic sections and to complete the diagnosis ( P>0.05). There was statistically significant difference in the diagnosis time required for doctor A using SonoVCADheart and two-dimensional echocardiography in fetuses with cardiovascular malformations ( P<0.05). However, there was no statistically significant difference in the time required in the normal fetus between SonoVCADheart and two-dimensional echocardiography ( P>0.05). The diagnostic coincidence rate of SonoVCADheart for fetuses with cardiac malformations is about 89.91%-90.83%. Conclusions:SonoVCADheart is a repeatable and stable novel fetal heart processing tool enabling displaying eight standard diagnostic sections of the fetal heart, and has potential clinical application value in the standardization of image acquisition and sequence display.

Study on diagnostic performance of fetal intelligent navigation echocardiography for congenital heart defect / 中华超声影像学杂志

Objective:To explore the sensitivity and specificity of fetal intelligent navigation echocardiography(FINE, 5D Heart) in the prenatal detection of congenital heart defect(CHD), and to compare its diagnostic performance with spatiotemporal image correlation(STIC) loop (STICloop).Methods:A total of 250 pregnant women having a singleton pregnancy in the second and third trimesters from April 2018 to May 2019 in Sir Run Run Shaw Hospital, Zhejiang University College of Medicine were enrolled in this prospective study. 2D ultrasound diagnosis has been made before acquiring STIC volume data set. After the appropriateness of each volume data set was preliminarily determined, all identifying informations were concealed and the appropriate volumes were randomly distributed to less experienced sonographer for analysis using 5D Heart software. The sensitivity and specificity, positive and negative likelihood ratios, as well as area under the receiver operating characteristic curve (AUC) of the two methods were determined respectively, and the differences between the two methods were statistically analyzed.Results:The diagnostic performance of 5D Heart for the prenatal detection of CHD was: sensitivity of 95.45% (105/110), specificity of 94.29% (132/140), positive likelihood ratio of 16.72, negative likelihood ratio of 0.05, and AUC of 0.95, respectively. Among cases with confirmed CHD, the 5D Heart diagnosis completely matched the final diagnosis in 77.27% (85/110). The diagnostic performance of STICloop for the prenatal detection of CHD was: sensitivity of 90.91% (100/110), specificity of 92.86% (130/140), positive likelihood ratio of 12.73, negative likelihood ratio of 0.10, and AUC of 0.92. The sensitivity and secificity of 5D Heart in diagnosing CHD were both higher than 90%, and it could successfully detect a broad spectrum of severe fetal CHD. Among cases with confirmed CHD, even the STICloop diagnosis completely matched the final diagnosis in 61.81%(68/110), its diagnostic accuracy was relatively lower than 5D Heart ( P=0.013). However, there were no statistical differences between the two methods in sensitivity and specificity(all P>0.05). Conclusions:The sesitivity and specifity of 5D Heart in diagnosis CHD were both higher than 90%, and it could successfully detect a broad spectrum of severe fetal CHD. STICloop could be used for preliminary screening of CHD, as it has the same high sensitivity and specificity as 5D Heart. Further examination may be recommended when fetal heart abnormalities are suspected.

Value of sonography based volume computer aided display heart in quantitative evaluation of fetal aortic and pulmonary artery diameters / 中华超声影像学杂志

Objective:To explore the feasibility of Sonography based Volume Computer Aided Display Heart (SonoVCADheart) in the display of the fetal ventricular outflow views, and compare diameters of fetal aorta (AO) and pulmonary artery (PA) measured by two-dimensional echocardiography (2DE) and SonoVCADheart.Methods:Eighty singleton fetuses in the second and third trimesters of pregnancy in January 2019 in Sir Run Run Shaw Hospital, Zhejiang University College of Medicine were enrolled. Conventional 2DE examinations were performed. The volume datasets were analyzed offline using the new automatic image processing software SonoVCADheart. The diameters of AO and PA were measured by 2DE and SonoVCADheart, respectively. Pearson correlation analysis was used to evaluate the correlation between the two methods. The consistency of the two methods was verified by Bland-Altman analysis, and he reliability of SonoVCADheart was assessed using the intraclass correlation coefficient (ICC).Results:Fetal ventricular outflow views were successfully obtained using SonoVCADheart in 73(91.2%) of 80 fetuses. There were good correlations between the two methods for measuring the diameters of AO and PA ( r=0.953, 0.971; all P<0.001). The 95% agreement limits of AO and PA were (-0.669, 0.568)mm and (-0.632, 0.580)mm, respectively. ICC demonstrated that SonoVCADheart achieved great repeatability both between and within observers. Conclusions:SonoVCADheart may have potentials for the quantitative evaluation of fetal ventricular outflow tracts with its good repeatability and reliability.

Analysis of immunological features of 135 patients with corona virus disease 2019 in Guangzhou City / 中华传染病杂志

Objective:To investigate the immunological features of 135 patients with corona virus disease 2019 (COVID-19), and to provide reference for the pathogenesis of the disease.Methods:The clinical and laboratory data of 135 confirmed COVID-19 patients in Guangzhou Eighth People′s Hospital from January 23 to February 29, 2020 were collected. The features of lymphocytes (CD4 + and CD8 + T lymphocytes, B lymphocytes, natural killer cells and natural killer T cells), and cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) of patients at a median of 19 (14, 27) days of admission were analyzed. Kruskal-Wallis test, Mann-Whitney U test, chi-square test and Spearman rank correlation were used for statistical analysis. Results:Patients were divided into three groups according to the relevant diagnostic criteria, including mild group (14 cases), ordinary group (92 cases) and severe group (29 cases). Decreased CD4 + T lymphocytes were found in 44.4% (60/135) patients, while decreased CD8 + T lymphocytes were found in 42.2%(57/135) patients. Compared to mild group and ordinary group, level of CD4 + T lymphocytes in severe group was significant lower ( Z=4.379 and 3.799, respectively, both P<0.01), and level of CD8 + T lymphocytes was also significant lower ( Z=2.684 and 3.306, respectively, P=0.022 and 0.003, respectively). Decreased B lymphocytes were found in 25.3% (24/95) patients and significant different among the three groups, with the lowest levels ((88(56, 189)/μL; Z=6.199, P=0.045) and most frequency of decreased levels ((52.2%(12/23); χ2=11.723, P=0.003) in the severe group. Compared to the mild group and the ordinary group, IL-6 level in severe group was significant higher ( Z=-4.022 and -4.108, respectively, both P<0.01) and IL-10 level was also significant higher ( Z=-3.261 and -4.006, respectively, both P<0.01). Similar levels of IL-2, IL-4, TNF-α and IFN-γ were found among three groups (all P>0.05). The IL-6 level was positively correlated with the persistence of viral shedding ( r=0.301, P=0.007). Conclusion:The immune-mediated inflammation may be the important cause of disease deterioration of COVID-19, which might be the key target of the treatment of severe cases.

Spatiotemporal correlation analysis of the etiology of hand, foot, and mouth disease in Dali Bai Autonomous Prefecture from 2013 to 2018 / 中华传染病杂志

Objective:To analyze the etiological spatialtemporal distribution characteristics of coxsackievirus A16 (CoxA16) and enterovirus 71 (EV71) in children with hand, foot, and mouth disease (HFMD) in Dali Bai Autonomous Prefecture, and to provide references for its prevention and control.Methods:Real-time polymerase chain reaction(PCR) was used to detect the etiology of children with HFMD in Dali Bai Autonomous Prefecture from January 1, 2013 to December 31, 2018, including CoxA16 and EV71. Spatialtemporal correlation analysis of CoxA16 and EV71 were performed by ArcGIS 10 and SaTScanv 9.6 softwares.Results:Among 3 527 pathogen samples, EV71 was dominant with 12.0%(91/758) in 2013, 40.4%(180/446) in 2014, and 26.7%(155/581) in 2017. CoxA16 was the dominant pathogen with 29.9%(162/541) in 2015, 40.0%(219/547) in 2016, and 13.8%(90/654) in 2018. According to the pathogen detection data from 2013 to 2018, the detection rate of CoxA16 pathogen was higher than that of EV71 ( χ2=1 128.72, P<0.05). CoxA16 and EV71 were aggregated from summer to autumn. CoxA16 was presented with clustered distribution ( Moran′ s index=0.344, P<0.05), and the hot spots of CoxA16 were Xiangyun County ( Z=2.72, P<0.01) and Midu County ( Z=1.68, P<0.1). The radius radiates was 39.00 km from the center of Xiangyun County (log likelihood ratio ( LLR)=40.178, P<0.05). EV71 was presented with discretely distribution ( Moran′ s index=-0.194, P>0.05), and the hot spots of EV71 were Heqing County ( Z=2.14, P<0.05), Jianchuan County ( Z=1.76, P<0.1) and Dali City ( Z=1.71, P<0.1). The main gathering area was the radiation radius of 64.21 km centered of Eryuan County ( LLR=39.376, P<0.05). Conclusions:There are spatiotemporal aggregations of CoxA16 and EV71 in childhood cases with HFMD. The monitoring should be strengthened, and the disease should be scientifically prevented and controlled.