ObjectiveTo investigate whether the CD151 YXXφ motif point mutant affects vascular permeability by regulating vesicle internalization and recycling. MethodsCD151 knockout （KO） and wild-type （WT） mice were used. A modified Miles assay was performed to compare vascular permeability in the dorsal and postauricular skin of the two groups of mice under vascular endothelial growth factor A （VEGF-A） stimulation. The CD151 YXXφ motif point mutant YALA was constructed and transfected into human endothelial cells （EA.hy926） using an adenoviral vector. Multiple experimental groups were set up to detect the permeability of endothelial cell monolayers to FITC-dextran under baseline conditions and after VEGF-A stimulation. Western blot （WB）， RT-qPCR， and immunofluorescence were used to examine the expression and distribution of VE-cadherin. The internalization rate of VE-cadherin was quantitatively compared using a cell surface biotinylation assay. Phalloidin was used to label F-actin to observe changes in cytoskeletal tension. ResultsThe Miles assay showed that under VEGF-A stimulation， dye extravasation in the dorsal and postauricular skin of KO mice was significantly higher than that in WT mice （all P<0.05）. At 60 min and 120 min after VEGF-A stimulation， the permeability of endothelial cell monolayers overexpressing the YALA mutant to FITC-dextran significantly increased （P<0.05）. WB and RT-qPCR results indicated that the YALA mutant did not affect the total protein or mRNA expression levels of VE-cadherin. Immunofluorescence revealed that the YALA mutant disrupted the continuous distribution of VE-cadherin on the cell membrane and its perinuclear co-localization with CD151 under VEGF-A stimulation. The cell surface biotinylation assay confirmed that the YALA mutant significantly reduced the internalization rate of VE-cadherin （P<0.05）. Cytoskeletal staining showed that the YALA mutant caused the formation of thick tension fibers in the actin cytoskeleton of endothelial cells， indicating cell contraction. ConclusionThe CD151 YXXφ motif point mutation affects vesicle internalization and recycling in endothelial cells， influences the expression and internalization of VE-cadherin， and consequently affects vascular permeability.

Objective:To evaluate the efficacy of an etoposide (Vp16) -intensified conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of relapsed/refractory acute myeloid leukemia (AML).Method:A retrospective analysis was conducted on the clinical data of 27 recipients with relapsed/refractory AML who underwent allo-HSCT using a Vp16-intensified conditioning regimen at Aerospace Center Hospital from January 2019 to January 2022. Transplantation-related complications and treatment outcomes were observed. Kaplan-Meier survival analysis was used to assess the overall survival (OS) and disease-free survival (DFS) rates.Result:Among the 27 recipients, there were 14 males and 13 females, with a median age of 41 years (range: 12~55 years). Except for one recipient who experienced primary graft failure, the remaining 26 recipients achieved hematopoietic reconstitution. The median neutrophil and platelet engraftment times were 13 days (range: 9~20 days) and 13.5 days (range: 11~33 days), respectively. Regimen-related toxicity (RRT) was mainly gastrointestinal toxicity and oral mucositis, and no deaths were attributed to RRT. A total of 12 recipients (44.44%) developed acute graft-versus-host disease (aGVHD), of whom 3 cases (11.11%) had grade III~IV aGVHD. Chronic GVHD (cGVHD) occurred in 13 recipients (48.15%), including 8 cases (29.63%) of extensive cGVHD. The median follow-up time after transplantation was 17 months (range: 1~48 months). Fifteen recipients (55.56%) survived without disease, while 12 recipients (44.44%) died— 9 due to relapse and 3 due to transplant-related complications. The 1-year overall survival and DFS rates were 74.07% and 59.26%, respectively; the 2-year overall survival and DFS rates were 59.26% and 55.56%, respectively. The 2-year relapse rate and transplant-related mortality (TRM) were 33.33% and 11.11%, respectively.Conclusion:The Vp16-intensified conditioning regimen in allo-HSCT appears to be a viable treatment option for patients with relapsed/refractory AML, offering favorable efficacy and manageable safety.

Objective : To explore the effect and mechanism of CD151 on vascular permeability by regulating vesicle internalization and recycling. Methods: Wild-type mice and CD151 knockout mice were divided into WT-con group, WT-model group, KO-con group and KO-model group, with 6 mice in each group. WT-model group and KO-model group were intraperitoneally injected with LPS to prepare sepsis ALI model, and WT-con group and KO-con group were intraperitoneally injected with phosphate buffer saline(PBS) as a control. 24 h after modeling, pulmonary vascular permeability was measured by Miles test. The siRNA silencing CD151 expression(si-CD151) and negative control si-NC were transfected into EA.hy 926 cells. The permeability of endothelial cell layer to FITC-dextran at different time points was observed under basic conditions and vascular endothelial growth factor-A(VEGF-A) stimulation conditions. Transcriptome sequencing of endothelial cells in si-CD151 group and si-NC group; the distribution and internalization of CD151 in each group were measured using immunofluorescence. Western blot and real-time quantitative RT-qPCR were used to detect the expression of VE-cadherin in si-CD151 groupand other groups. The distribution and internalization of VE-cadherin in each group were measured using immunofluorescence. Results : Miles experiment results indicated that dye exudation in lung tissue of WT-model group was significantly higher than that of WT-con group(P<0.01). The dye exudation in the lung tissue of KO-model group increased compared with WT-model group(P<0.05). The results of endothelial cell layer permeability test showed that the permeability of FITC-dextran in si-CD151 group was significantly higher than that in control group after VEGF-A stimulation for 30, 60 and 120 min(P<0.05). Transcriptome sequencing results suggested that CD151 in endothelial cells was closely related to vesicle-mediated transport. Compared with other groups, protein and mRNA levels of VE-cadherin in CD151 knockdown endothelial cells was significantly lower(allP<0.01). The immunofluorescence assay demonstrated that after VEGF-A stimulation, the decrease of CD151 expression significantly impaired the expression of VE-cadherin at cell-cell contacts and reduced the CD151-VE-cadherin colocalization in the perinuclear region compared with other groups. Conclusion The absence of CD151 affects the internalization and recycling of endothelial cell vesicles, affects the expression and internalization of VE-cadherin, and then influences vascular permeability.

Objective:To evaluate the efficacy of an etoposide (Vp16) -intensified conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of relapsed/refractory acute myeloid leukemia (AML).Method:A retrospective analysis was conducted on the clinical data of 27 recipients with relapsed/refractory AML who underwent allo-HSCT using a Vp16-intensified conditioning regimen at Aerospace Center Hospital from January 2019 to January 2022. Transplantation-related complications and treatment outcomes were observed. Kaplan-Meier survival analysis was used to assess the overall survival (OS) and disease-free survival (DFS) rates.Result:Among the 27 recipients, there were 14 males and 13 females, with a median age of 41 years (range: 12~55 years). Except for one recipient who experienced primary graft failure, the remaining 26 recipients achieved hematopoietic reconstitution. The median neutrophil and platelet engraftment times were 13 days (range: 9~20 days) and 13.5 days (range: 11~33 days), respectively. Regimen-related toxicity (RRT) was mainly gastrointestinal toxicity and oral mucositis, and no deaths were attributed to RRT. A total of 12 recipients (44.44%) developed acute graft-versus-host disease (aGVHD), of whom 3 cases (11.11%) had grade III~IV aGVHD. Chronic GVHD (cGVHD) occurred in 13 recipients (48.15%), including 8 cases (29.63%) of extensive cGVHD. The median follow-up time after transplantation was 17 months (range: 1~48 months). Fifteen recipients (55.56%) survived without disease, while 12 recipients (44.44%) died— 9 due to relapse and 3 due to transplant-related complications. The 1-year overall survival and DFS rates were 74.07% and 59.26%, respectively; the 2-year overall survival and DFS rates were 59.26% and 55.56%, respectively. The 2-year relapse rate and transplant-related mortality (TRM) were 33.33% and 11.11%, respectively.Conclusion:The Vp16-intensified conditioning regimen in allo-HSCT appears to be a viable treatment option for patients with relapsed/refractory AML, offering favorable efficacy and manageable safety.

Objective To investigate the correlations of serum Apelin-13 and fatty acid binding protein 4 (FABP4) levels with metabolic and bone metabolic indicators in postmenopausal women with different bone mass. Methods A total of 145 postmenopausal women were selected as subjects and divided into three groups based on bone mineral density (BMD) test results: normal bone mass group(49 cases), osteopenia (ON) group(51 cases), and osteoporosis (OP) group(45 cases). Serum Apelin-13, FABP4 levels, bone metabolic indicators, and biochemical indicators were measured and compared among the three groups. Spearman correlation analysis was used to analyze the correlations of Apelin-13, FABP4, and other indicators with BMD. Multivariate Logistic regression analysis was performed to analyze the risk factors for OP, and the receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of serum Apelin-13 for postmenopausal osteoporosis (PMOP). Results The serum Apelin-13 level in the OP group was lower than that in the ON group and the normal bone mass group (P < 0.05). No significant difference in serum FABP4 levels was found among the three groups (P>0.05). The levels of serum parathyroid hormone (PTH), alkaline phosphatase (ALP), type Ⅰ procollagen amino-terminal propeptide (PⅠNP), type Ⅰ collagen cross-linked C-terminal peptide (CTXⅠ), and bone-specific alkaline phosphatase (BALP) in the OP group were higher than those in the ON group and the normal bone mass group (P < 0.05). Lumbar post-menopause BMD was positively correlated with serum Apelin-13 levels (P < 0.05), but had no correlation with serum FABP4 levels (P>0.05). Lumbar BMD was negatively correlated with serum PTH, ALP, PⅠNP, CTXⅠ, BALP, and age (P < 0.05), but positively correlated with body weight, body mass index, T-score, fasting insulin, and insulin resistance index (P < 0.05). Multivariate Logistic regression analysis showed that serum Apelin-13, PTH, ALP, PⅠNP, CTXⅠ, and BALP levels were independent factors influencing the occurrence of OP in postmenopausal women (P < 0.05). ROC curve results showed that the optimal cut-off value of serum Apelin-13 for predicting PMOP was 18.51 pg/mL, with an area under the curve of 0.716, a sensitivity of 70.0%, and a specificity of 64.4%. Conclusion Apelin-13 is lowly expressed in the serum of PMOP patients, and its expression level is closely related to lumbar BMD, which may serve as an early screening indicator and potential therapeutic target for PMOP.

Objective:To investigate the relationship between fat-to-muscle mass ration(FMR) and cognitive impairment in older adults with type 2 diabetes mellitus and to further explore the gender difference.Methods:A cross-sectional study was conducted on 768 elderly type 2 diabetes mellitus patients(≥60 years old) who were hospitalized in the Endocrinology Ward of Tianjin Union Medical Center from July 2018 to May 2022. The body composition was measured by bioelectrical impedance analysis(BIA), and the cognitive function was assessed using mini mental state examination(MMSE) and Montreal cognitive assessment(MoCA). According to the cognitive scale screening, type 2 diabetes mellitus patients were divided into normal cognitive function group and cognitive impairment group with stratified analysis by gender. New FMR indicators were developed based on BIA measurements, including fat mass(FM)/ appendicular skeletal muscle mass(ASM), FM/ skeletal muscle mass(SMM), and FM/ fat free mass(FFM). Binary logistic regression was used to analyze the relationship between FMRs and cognitive impairment risk, stratified by gender.Results:FMR indicators were not associated with cognitive impairment in females. In males, after adjusting for multiple factors, higher FMR values were significantly associated with an increased risk of cognitive impairment(FM/FFM: OR=1.722, 95% CI 1.230-2.409, P=0.002; FM/SMM: OR=1.337, 95% CI 1.118-1.599, P=0.001; FM/ASM: OR=1.240, 95% CI 1.077-1.427, P=0.003) and was independent of body mass index. For FM/FFM, every 0.1-unit increase raised the risk of cognitive impairment by 77.2%. FMR had a stronger association with cognitive impairment in the normal-weight group(body mass index<25 kg/m 2) than in the overweight/obese group(body mass index≥25 kg/m 2). The prevalence of cognitive impairment increased progressively with higher FMR . Conclusion:In men over 60 years with type 2 diabetes mellitus, FMR may be an independent risk factor for cognitive function.

Objective:To investigate the relationship between fat-to-muscle mass ration(FMR) and cognitive impairment in older adults with type 2 diabetes mellitus and to further explore the gender difference.Methods:A cross-sectional study was conducted on 768 elderly type 2 diabetes mellitus patients(≥60 years old) who were hospitalized in the Endocrinology Ward of Tianjin Union Medical Center from July 2018 to May 2022. The body composition was measured by bioelectrical impedance analysis(BIA), and the cognitive function was assessed using mini mental state examination(MMSE) and Montreal cognitive assessment(MoCA). According to the cognitive scale screening, type 2 diabetes mellitus patients were divided into normal cognitive function group and cognitive impairment group with stratified analysis by gender. New FMR indicators were developed based on BIA measurements, including fat mass(FM)/ appendicular skeletal muscle mass(ASM), FM/ skeletal muscle mass(SMM), and FM/ fat free mass(FFM). Binary logistic regression was used to analyze the relationship between FMRs and cognitive impairment risk, stratified by gender.Results:FMR indicators were not associated with cognitive impairment in females. In males, after adjusting for multiple factors, higher FMR values were significantly associated with an increased risk of cognitive impairment(FM/FFM: OR=1.722, 95% CI 1.230-2.409, P=0.002; FM/SMM: OR=1.337, 95% CI 1.118-1.599, P=0.001; FM/ASM: OR=1.240, 95% CI 1.077-1.427, P=0.003) and was independent of body mass index. For FM/FFM, every 0.1-unit increase raised the risk of cognitive impairment by 77.2%. FMR had a stronger association with cognitive impairment in the normal-weight group(body mass index<25 kg/m 2) than in the overweight/obese group(body mass index≥25 kg/m 2). The prevalence of cognitive impairment increased progressively with higher FMR . Conclusion:In men over 60 years with type 2 diabetes mellitus, FMR may be an independent risk factor for cognitive function.

Objective:To assess the altered right atrial(RA) function using two-dimensional speckle-tracking imaging(2D-STI) in patients with persistent pulmonary hypertension of the newborn(PPHN), and investigate the diagnostic value of different right heart strain parameters in PPHN.Methods:Ultrasound images of 42 newborns with clinically confirmed diagnosis of PPHN in the neonatal intensive care unit of Shenzhen Children′s Hospital (median gestational age 37 + 1 weeks, median age 6 d) and 30 normal newborns (control group, median gestational age 37 + 3 weeks, median age 6.5 d) from January 2020 to January 2023 were retrospectively analyzed, all with gestational age ≥34 gestational weeks. 2D-STI was applied to evaluate RA function: RA strain(RA LS) and area change fraction(RA FAC), where RA LS included RA reservoir strain (εs), RA conduit strain (εe) and RA active contract strain (εa), while evaluating right ventricle(RV) function: RV global longitudinal strain(RV GLS), RV FAC, etc. And the degree of pulmonary artery pressure(PAP) was assessed by tricuspid regurgitation velocity(TRV). The above parameters were compared between the PPHN group and the control group, and the correlations between RA function parameters, RV function parameters and PAP in PPHN group were analyzed. The area under ROC curve (AUC) was used to compare the accuracy of each parameter in the evaluation of impaired cardiac function in PPHN patients. Results:Compared with the control group, RA function (εs, εe, εa and RA FAC) were impaired in PPHN patients (all P<0.05). εs was positively correlated with RV GLS, RA FAC ( r=0.494, 0.356, both P<0.05) and negatively correlated with minimum right atrial area (RAA min), pulmonary artery diameter (PAD), and tricuspid annular internal diameter ( rs=-0.285, r=-0.495, -0.396; both P<0.05); εe was negatively correlated with PAD ( rs=-0.256, P<0.05); εa was positively correlated with RV GLS ( r=0.499, P<0.05) and negatively correlated with PAD and tricuspid annular internal diameter ( r=-0.390, -0.380; both P<0.05); RA FAC was positively correlated with RV GLS ( r=0.365, P<0.05) and negatively correlated with PAD and tricuspid annular internal diameter ( r=-0.439, -0.328; both P<0.05). RA LS and RA FAC had no correlations with TRV-estimated PAP ( P>0.05). ROC analysis showed that the sensitivity and specificity of εs<40.50% for diagnosing PPHN was 0.905 and 0.800, respectively, with an AUC of 0.929; the sensitivity and specificity of RV GLS<18.55% for diagnosing PPHN were 0.905 and 0.900, respectively, with an AUC of 0.963; εs combined with RV GLS was the best indicator for early detection of right heart functional impairment in PPHN, with sensitivity and specificity of 0.905 and 1.000, respectively, and AUC was 0.985. Conclusions:RA function and RV function are both impaired in PPHN patients. εs combined with RV GLS is the best indicator for early assessment of right heart function impairment and diagnosis of PPHN.

Objective::This study investigates the efficacy of analyzing fetal heart rate (FHR) signals based on Artificial Intelligence to obtain a baseline calculation and identify accelerations/decelerations in the FHR through electronic fetal monitoring during labor.Methods::A total of 43,888 cardiotocograph(CTG) records of female patients in labor from January 2012 to December 2020 were collected from the NanFang Hospital of Southern Medical University. After filtering the data, 2341 FHR records were used for the study. The ObVue fetal monitoring system, manufactured by Lian-Med Technology Co. Ltd., was used to monitor the FHR signals for these pregnant women from the beginning of the first stage of labor to the end of delivery. Two obstetric experts together annotated the FHR signals in the system to determine the baseline as well as accelerations/decelerations of the FHR. Our cardiotocograph network (CTGNet) as well as traditional methods were then used to automatically analyze the baseline and acceleration/deceleration of the FHR signals. The results of calculations were compared with the annotations provided by the obstetric experts, and ten-fold cross-validation was applied to evaluate them. The root-mean-square difference (RMSD) between the baselines, acceleration F-measure (Acc.F-measure), deceleration F-measure (Dec.F-measure), coefficient of synthetic inconsistency (SI) and the morphological analysis discordance index (MADI) were used as evaluation metrics. The data were analyzed by using a paired t-test. Results::The proposed CTGNet was superior to the best traditional method, proposed by Mantel, in terms of the RMSD.BL (1.7935 ± 0.8099 vs. 2.0293 ± 0.9267, t=-3.55 , P=0.004), Acc.F-measure (86.8562 ± 10.9422 vs. 72.2367 ± 14.2096, t= 12.43, P <0.001), Dec.F-measure (72.1038 ± 33.2592 vs. 58.5040 ± 38.0276, t= 4.10, P <0.001), SI (34.8277±20.9595 vs. 54.8049 ± 25.0265, t=-9.39, P <0.001), and MADI (3.1741 ± 1.9901 vs. 3.7289 ± 2.7253, t= -2.74, P= 0.012). The proposed CTGNet thus had significant advantages over the best traditional method on all evaluation metrics. Conclusion::The proposed Artificial Intelligence-based method CTGNet delivers good performance in terms of the automatic analysis of FHR based on cardiotocograph data. It promises to be a key component of smart obstetrics systems of the future.

Objective::This study investigates the efficacy of analyzing fetal heart rate (FHR) signals based on Artificial Intelligence to obtain a baseline calculation and identify accelerations/decelerations in the FHR through electronic fetal monitoring during labor.Methods::A total of 43,888 cardiotocograph(CTG) records of female patients in labor from January 2012 to December 2020 were collected from the NanFang Hospital of Southern Medical University. After filtering the data, 2341 FHR records were used for the study. The ObVue fetal monitoring system, manufactured by Lian-Med Technology Co. Ltd., was used to monitor the FHR signals for these pregnant women from the beginning of the first stage of labor to the end of delivery. Two obstetric experts together annotated the FHR signals in the system to determine the baseline as well as accelerations/decelerations of the FHR. Our cardiotocograph network (CTGNet) as well as traditional methods were then used to automatically analyze the baseline and acceleration/deceleration of the FHR signals. The results of calculations were compared with the annotations provided by the obstetric experts, and ten-fold cross-validation was applied to evaluate them. The root-mean-square difference (RMSD) between the baselines, acceleration F-measure (Acc.F-measure), deceleration F-measure (Dec.F-measure), coefficient of synthetic inconsistency (SI) and the morphological analysis discordance index (MADI) were used as evaluation metrics. The data were analyzed by using a paired t-test. Results::The proposed CTGNet was superior to the best traditional method, proposed by Mantel, in terms of the RMSD.BL (1.7935 ± 0.8099 vs. 2.0293 ± 0.9267, t=-3.55 , P=0.004), Acc.F-measure (86.8562 ± 10.9422 vs. 72.2367 ± 14.2096, t= 12.43, P <0.001), Dec.F-measure (72.1038 ± 33.2592 vs. 58.5040 ± 38.0276, t= 4.10, P <0.001), SI (34.8277±20.9595 vs. 54.8049 ± 25.0265, t=-9.39, P <0.001), and MADI (3.1741 ± 1.9901 vs. 3.7289 ± 2.7253, t= -2.74, P= 0.012). The proposed CTGNet thus had significant advantages over the best traditional method on all evaluation metrics. Conclusion::The proposed Artificial Intelligence-based method CTGNet delivers good performance in terms of the automatic analysis of FHR based on cardiotocograph data. It promises to be a key component of smart obstetrics systems of the future.