Effects of 0.2% chloroprocaine combined with ropivacaine on epidural labor analgesia and EC50 of ropivacaine / 中国药房

OBJECTIVE To investigate the effects of 0.2% chloroprocaine combined with ropivacaine on epidural labor analgesia and median effective concentration （EC50） of ropivacaine. METHODS Totally 67 parturients who scheduled for vaginal delivery and required epidural labor analgesia were collected from our hospital from July to October 2023 and randomly divided into RL group （33 cases） and R group （34 cases）. The concentration of ropivacaine was determined by modified Dixon sequential method. RL group was given 0.2% Chloroprocaine hydrochloride injection+Ropivacaine hydrochloride injection+0.4 μg/mL Sufentanil citrate injection； R group was given Ropivacaine hydrochloride injection+0.4 μg/mL Sufentanil citrate injection. EC50 of ropivacaine， analgesic effect during delivery， total dosage of analgesic drugs， analgesic satisfaction score， the incidence of adverse reactions， delivery status， and Apgar score of newborns were observed in two groups. RESULTS EC50 of ropivacaine， onset time， remedial analgesia rate， the incidence of perineal distension and breakthrough pain and total dosage of analgesic drugs of RL group were significantly lower than R group， and analgesic satisfaction score was significantly higher than R group （P＜0.05）. There was no statistical significance in the incidence of adverse reactions such as numbness， weakness， and chills in the lower limbs， or the duration of labor， amount of bleeding， mode of delivery， and Apgar score of newborns between 2 groups （P＞0.05）. CONCLUSIONS For epidural labor analgesia， 0.2% chloroprocaine combined with ropivacaine can reduce EC50 of ropivacaine， improve analgesia effect and have good safety.

Application of knowledge distillation technology for fine segmentation of three-vessel and trachea views in fetal echocardiographic images / 中华超声影像学杂志

Objective:To explore the application value of fetal heart ultrasound image segmentation network model based on knowledge distillation technology in the fine segmentation of fetal heart ultrasound image at three-vessel and trachea (3VT) views.Methods:One thousand and three hundred fetals were retrospectively collected from Sir Run Run Shaw Hospital, Zhejiang University College of Medicine from January 2016 to December 2021, the two-dimensional grayscale ultrasound images of fetal heart at 3VT views were analyzed and then divided into training, validation, and test sets. The training and validation sets were used to construct the auxiliary diagnostic network models, and the test set was used to test the reliability of different network models (U-Net, DeepLabv3+ ). The 3VT views were collected and annotated by an experienced doctor as the reference standard. The intersection over union (IoU), pixel accuracy (PA) and Dice coefficient (Dice) were used as the 3 indexes to evaluate the segmentation accuracy, and the diagnostic efficiency of the training model was evaluated. The training model and the most commonly used segmentation models were identified, and the results were compared. A total of 101 images were randomly selected and assigned to junior doctors, AI and junior doctors assisted AI interpretation. Bland-Altman images were drawn to evaluate their consistency with the reference standard, and the results were compared.Results:The training model of knowledge distillation algorithm achieved better results than U-Net, DeepLabv3+ models on all evaluation indexes, and the average IoU, PA and Dice were 68.6%, 81.4% and 81.3%, respectively. Compared with the U-Net model and DeepLabv3+ model, more accurate segmentation boundaries were obtained by the knowledge distillation algorithm training model, and the quantitative evaluation indexes were improved. With the aid of the model, the diagnostic accuracy of junior doctors was improved.Conclusions:The knowledge distillation algorithm training model segmentation method can identify the anatomical structure of the fetal heart in the 3VT view of the fetal heart ultrasound image, and the recognition result is obviously better than other related methods, and can improve the accuracy of image recognition for doctors with low experience.

Correlation of RBP7 mRNA Expression in Breast Cancer Tissues with Tumor Immune Cell Infiltration and Prognosis Based on TCGA Database / 现代检验医学杂志

Objective To explore the role of retinol binding protein 7(RBP7)in breast cancer by bioinformatics.Methods R sofrware was used to explore the differential expression of the RBP7 gene in breast cancer by the cancer genome atlas(TCGA)dataset and the human protein atlas(HPA).Relationship between RBP7 and clinical data of breast cancer was evaluated by Kaplan-Meier survival analysis and receiver operating characteristic(ROC)curves.Correlation between high and low RBP7 expression groups and different tumor-infiltrating immune cells(TIICs)were analyzed based on the TCGA database.Gene set enrichment analysis(GSEA)was used to assess the distribute trends of RBP7 in gene tables sorted by phenotypic relatedness.Results RBP7 mRNA expression levels were down-regulated in breast cancer compared to paracancerous tissues,which were expressed in the nucleus.ROC curve analysis showed that the area under curve(AUC)of RBP7 for the diagnosis of breast cancer was 0.943(95%CI:0.926～0.960),and the best cut-off value of RBP7 was 6.29,with a sensitivity and specificity of 82.32%and 93.69%,respectively.Kaplan-Meier survival analysis showed that low expression of RBP7 was associated with overall survival rate in breast cancer patients(HR=0.68,95%CI:0.49～0.93,P=0.017),indicating that RBP7 was an independent risk factor for breast cancer.Spearman correlation showed that RBP7 was positively associated with pDC cells and NK cells(r=0.290,0.253,all P<0.05),and negatively associated with Th2 cells(r=-0.217,P<0.05)in breast cancer.GSEA showed that RBP7 was enriched in pathways such as adipogenesis,ribosome,peptiden ligand binding receptors,and calcium signaling pathway(all P<0.001).Conclusion RBP7 affects the occurrence and development of breast cancer,which may be a potential biomarker and therapeutic target for breast cancer.

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.

Associations between abnormal electroencephalogram microstates and childhood emotional abuse in adolescent depression / 中南大学学报(医学版)

Objective:Childhood traumatic experiences greatly influenced the brain network activities of patients with depression,and there is an urgent need to explore the temporal dynamics for these changes.This study aims to investigate the abnormalities of resting-state electroencephalogram(EEG)microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. Methods:Using resting-state EEG microstate analysis,we explored the temporal dynamics of brain activity in patients with adolescent depression.This study selected 66 adolescents with depression as a patient group,and 27 healthy adolescents as a healthy control group.A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates.Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. Results:In this study,significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group.Notably,there was a statistically significant difference(P＜0.05)in the occurrence of microstate A across 2 groups,exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores(Spearman's rho=-0.31,P=0.013).Furthermore,patient-specific,non-random transitions from microstate B to A(Spearman's rho=-0.30,P=0.015)and C to A(Spearman's rho=-0.31,P=0.013)were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group,showing statistically significant differences when comparing to the healthy controls(P＜0.05).Upon stratification into quartiles based on the emotional abuse factor scores,the occurrence of microstate A,as well as the transition rates from microstates B to A and C to A,retained statistical significance following adjustment for multiple comparisons(all P＜0.05). Conclusion:The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse.Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks.EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.

Quantitative study of atrial diameter and Z-score of normal fetuses in middle and late trimester by echocardiography / 中华超声影像学杂志

Objective:To analyze the correlation between left and right atrial diameters and fetal biological growth parameters of normal fetuses in middle and late trimester, and to establish normal reference and Z-score model for left and right atria.Methods:Three hundred and ninety-two fetuses in middle and late trimester were prospectively selected from July 2022 to October 2022 in Sir Run Run Shaw Hospital.Non-cardiac biometric parameters included biparietal diameter (BPD), femoral length (FL), and gestational age (GA) based on menstrual age were assessed.Left and right atrial widths (LAW, RAW) and atrial lengths (LAL, RAL) at end-systole, left and right atrial areas (LAA, RAA) at end-systole and the heart area (HA) at end-diastole were measured in standard apical four-chamber or basal four-chamber view. The ratio of RA and LA transverse diameters (RAW/LAW), the ratio of RA and LA length diameters (RAL/LAL), ratio of RA and LA area (RAA/LAA), spherical index of the ratio of RA and LA length to transverse diameter (RASI, LASI), ratio of LA and RA area to heart area (LAA/HA, RAA/HA) were calculated. The best regression equation was established using GA, BPD and FL as independent variables and LAL, LAW, LAA, RAL, RAW, RAA as dependent variable. The correlation between the standard deviation (SD) and the independent variables GA, BPD and FL was analyzed, and then the above statistics were used to calculate the corresponding Z-score for each variable of RA and LA using the regression equation.Results:①Significant positive correlations were found between LAW, RAW, LAL, RAL, LAA and RAA with the increase of GA, BPD and FL, and the highest degree of correlation between RAA, LAA and GA was denoted ( r=0.927, 0.920, all P<0.001). ②Taking GA as an example, there was no significant correlation between RAL/LAL, RAW/LAW and GA ( r=-0.064, 0.077; all P>0.05). RAA/LAA showed a very weak positive correlation with GA ( r=0.106, P=0.037), with normal reference values of 1.002±0.091, 1.091±0.093, 1.059±0.090, respectively. Interestingly RAL/LAL was found close to 1, while RAW/LAW and RAA/LAA were always >1. No significant correlations were found between LAA/HA, RAA/HA and GA ( r=0.003, 0.056; all P>0.05), with normal reference values of 0.155±0.026, 0.163±0.026, respectively, and RAA/HA was found larger than LAA/HA. LASI showed a very weak positive correlation with GA ( r=0.112, P=0.027), while there was no significant correlation between RASI and GA ( r=0.003, P>0.05), the normal reference values were 1.068±0.113, 0.980±0.105, respectively. ③The SD of LAL, LAW, etc.showed a simple linear relationship with the independent variables. Taking RAA and GA as examples, the linear regression equation for RAA was Y=-1.690+ 0.107 0GA ( r=0.927, P<0.001) and the linear regression equation for RAA-SD was Y=-0.107+ 0.010 4GA ( r=0.320, P<0.001). The Z-scores for LAL, LAW, LAA, RAL, RAW and RAA were relatively constant with the growth of GA, BPD and FL, with the corresponding Z-scores for GA were -1.817~3.631( r=0.000 3), -1.605~2.995( r<-0.000 1), -1.700~3.107( r<0.000 1), -1.617~3.466( r=0.000 1), -1.491~3.025( r<-0.000 1), -1.566~3.104( r=0.000 2), respectively. Conclusions:This study preliminarily establish the reference value ranges and Z-score of atrial diameters in normal fetuses during middle and late trimester, providing a reference basis for accurate quantitative evaluation of fetal atrial development and analysis of fetal congenital heart abnormalities, and contributing to the early detection of pathological conditions leading to abnormal atrial size.

Analysis for Key Points of Registration Applications and Difficulties of Process Control of 3D Printed Customized Dentures / 中国医疗器械杂志

With the highlighted advantages of 3D printing technology in the field of dental prosthodontics, there is increasing in the numbers of registration applications for additive manufacturing customized dentures. However, there is still a lack of unified analysis in the core elements of process control, the key points of registration and the safety production quality control. Based on the current research status of the industry, the study is intended to clarify confusion and difficulties, deeply analyse the mechanism of the product defects, sort the core elements of process control, then try to establish a systematic evaluation system from product performance research, key process verification, production quality control and the description of registration files, so that it can provide help for practitioners to clarify research direction, establishing quality management system, improving the efficiency of registration and ensuring product quality.

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.

Supervillin Isoform 4 (SV4) Regulates Mitosis by Enhancing Aurora A Activity / 中国生物化学与分子生物学报

Mitosis is important for cell proliferation in eukaryotes, and chromosome replication and accurate separation are essential for cell division. Supervillin is a membrane and microfilament actin binding protein. Previous studies have found that it regulates the dynamic changes of the cortical distribution of F-actin and myosin II in cytokinesis, thus ensuring the correct distribution of the contraction ring and participating in the final completion of cytoplasm divisions. But it is not clear whether it functions during metaphase. Supervillin has several splicing isomers, among which supervillin isoform 4 (SV4) is the largest splicing isomer. In this study, the expression of SV4 in cells was reduced by the RNA interference method, and the dynamic process of mitosis and the morphology of astral spindles were detected and observed by real-time microscopy and immunofluorescence staining, and the potential molecular mechanism of SV4 in mitosis was analyzed. The results showed abnormal cell divisions after SV4 reduction: delayed transition from metaphase to anaphase (P<0.001), abnormal assembly of microtubules, a twofold-increase of the number of cells with multipolar spindles, and decreased γ-tubulin signaling in the centrosome (P<0.001). Through GST pull-down and mass spectrometry experiments, we found that SV4 and Aurora A bind to each other, and SV4 regulates the localization and activation of Aurora A in the centrosome during mitosis. In summary, supervillin plays an important role in mitosis. The isomer SV4 regulates spindle integrity and γ-tubulin recruitment by interacting with Aurora A and recruiting it for proper localization and activation in the centrosome during the metaphase, thus promoting the correct assembly of bipolar spindles and ensuring the accurate separation of chromosomes and the smooth progress of mitosis.

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.

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.

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.

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.

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.

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.

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.

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.

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.