1.Imaging assessment of osteosarcoma chemotherapy efficacy based on multi-scale lesion attention network
Jie ZANG ; Ze-Qun SONG ; Zhen-Yu TANG ; Fang-Zhou HE ; Chao-Wei DING ; Ling-Feng WANG ; Xiao-Dong TANG
Acta Anatomica Sinica 2025;56(1):30-36
Objective To propose a high-precision deep learning-based image assessment method of osteosarcoma chemotherapy efficacy for clinical treatment,as existing methos have low accuracy of osteosarcoma assessment.Methods The low incidence of osteosarcoma led to the small scale of its imaging data and the problem of imbalance in data categories.This study combined deep learning with clinical medical information,combined the bone sarcoma generation module of BoneGAN and the scale lesion information capture module,and proposed OMLA-Net,a deep learning assessment network for chemotherapy effect of bone sarcoma based on multi-scale lesion attention network,which achieved computer-aided bone tumor assessment with integrated data augmentation and focused lesion information through pre-training and generalized loss training.Results In this study,40 cases of osteosarcoma MRI data were used as the basis for the comparison test on the generated dataset,and the OMLA-Net assessment outperformed the SOTA method Conv-LSTM-GAN in terms of the assessment effects such as accuracy and F1 scores,and the difference was statistically significant(Bootstrap statistical method P<0.05);the subsequent K-fold cross-validation ablation experiments further demonstrated the effectiveness of each module proposed by OMLA-Net.Conclusion OMLA-Net can effectively perform the impact assessment of chemotherapy effect on osteosarcoma,which provides a new idea for subsequent clinical application.
2.Synthesis and Application of Benzimidazole-Carbazole-based Fluorescent Probe for Detection of Phosgene
Guang-Mei XU ; Ze-Yu SONG ; Qin-Qin TIAN ; Xiao-Hong ZHU ; Jin-Chao SHEN ; Wei HE
Chinese Journal of Analytical Chemistry 2025;53(10):1705-1713,中插37-中插41
Phosgene is a highly reactive chemical substance and a prevalent chemical warfare agent,and it is vitally important for rapid and accurate detection of phosgene to counteract terrorist threats and industrial accidents.In this work,a phosgene probe,designated as SX-Pho,which incorporated benzimidazole and hydroxyl groups as recognition motifs,was prepared through Suzuki coupling and Debus-Radziszewski methodologies to incorporate an electron-donating carbazole moiety.This probe exhibited a large Stokes shift(Approximately 130 nm).Upon exposure to triphosgene/triethylamine conditions(in situ phosgene generation),the fluorescence emission of probe at 470 nm underwent significant quenching,with a 20-fold reduction in intensity,while the fluorescence lifetime decreased from 3.30 ns to 3.06 ns.Concentration titration experiments demonstrated that SX-Pho achieved a lower detection limit of 57.8 nmol/L with high specificity and interference resistance.Preton nuclear magnetic resonance spectroscopy(1H NMR),high-resolution mass spectrometry,and density functional theory(DFT)calculations confirmed the cyclization reaction between hydroxyl groups,imines,and phosgene.The extent of overlap between the highest occupied molecular orbital(HOMO)and the lowest unoccupied molecular orbital(LUMO)was notably decreased,leading to the suppression of radiative transitions.The energy gap underwent a reduction of 0.43 eV,while the non-radiative transition was augmented,resulting in fluorescence quenching and achieving rapid detection of phosgene.Based on this,probe-loaded test strips were prepared.The color change under 365 nm illumination allowed visual discrimination of phosgene at concentrations below 20 μL/L.Furthermore,using a smartphone's built-in RGB application to measure the intensity of the blue(B)channel after the test strips were exposed to phosgene enabled both qualitative and quantitative detection.The detection range was 1.82-50 μL/L,with a limit of detection(LOD)of 1.814 μL/L.
3.Treating Type 2 Diabetic Nephropathy by Down-regulating NOX4 to Inhibit the Oxidative Stress Pathway in Mesenchymal Stem Cells
Shu-Qi FENG ; Guo-Rong JIN ; Qun-Hang XUE ; Min HE ; Ze-Hang WANG ; Jia-Xin YAO ; Long CHEN ; Yu-Jiao WANG ; An-Xiu ZHANG ; Sheng HE ; Bing-Rui ZHOU ; Jun XIE
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):730-740
Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P<0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P<0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P<0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P<0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P<0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.
4.Prognostic Value of Dynamic Monitoring of WT1 Expression Levels for Relapse and Overall Survival in AML Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation During First Complete Remission
Xiao-Ya HE ; Han-Yun REN ; Yu-Jun DONG ; Li JI ; Qing-Yun WANG ; Yuan LI ; Yue YIN ; Ze-Yin LIANG ; Qian WANG ; Wei-Lin XU ; Jin-Ping OU ; Bing-Jie WANG ; Wei LIU
Journal of Experimental Hematology 2025;33(6):1790-1796
Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0%.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1%.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26%(range:0%-23.64%),with an upper quartile value of 0.74%.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels>0.74%at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P<0.001)compared to patients with WT1 levels ≤0.74%.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level>0.74%at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95%CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95%CI:0.749-16.100,P=0.037).Only WT1 level>0.74%at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95%CI:2.402-19.738,P<0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.
5.Prognostic Value of Dynamic Monitoring of WT1 Expression Levels for Relapse and Overall Survival in AML Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation During First Complete Remission
Xiao-Ya HE ; Han-Yun REN ; Yu-Jun DONG ; Li JI ; Qing-Yun WANG ; Yuan LI ; Yue YIN ; Ze-Yin LIANG ; Qian WANG ; Wei-Lin XU ; Jin-Ping OU ; Bing-Jie WANG ; Wei LIU
Journal of Experimental Hematology 2025;33(6):1790-1796
Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0%.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1%.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26%(range:0%-23.64%),with an upper quartile value of 0.74%.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels>0.74%at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P<0.001)compared to patients with WT1 levels ≤0.74%.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level>0.74%at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95%CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95%CI:0.749-16.100,P=0.037).Only WT1 level>0.74%at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95%CI:2.402-19.738,P<0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.
6.Treating Type 2 Diabetic Nephropathy by Down-regulating NOX4 to Inhibit the Oxidative Stress Pathway in Mesenchymal Stem Cells
Shu-Qi FENG ; Guo-Rong JIN ; Qun-Hang XUE ; Min HE ; Ze-Hang WANG ; Jia-Xin YAO ; Long CHEN ; Yu-Jiao WANG ; An-Xiu ZHANG ; Sheng HE ; Bing-Rui ZHOU ; Jun XIE
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):730-740
Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P<0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P<0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P<0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P<0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P<0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.
7.A multicenter retrospective cohort study on the attributable risk of patients with Acinetobacter baumannii sterile body fluid infection
Lei HE ; Dao-Bin JIANG ; Ding LIU ; Xiao-Fang ZHENG ; He-Yu QIU ; Shu-Mei WU ; Xiao-Ying WU ; Jin-Lan CUI ; Shou-Jia XIE ; Qin XIA ; Li HE ; Xi-Zhao LIU ; Chang-Hui SHU ; Rong-Qin LI ; Hong-Ying TAO ; Ze-Fen CHEN
Chinese Journal of Infection Control 2024;23(1):42-48
Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3%,and that of non-infected group was 23.1%,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2%(95%CI:-2.3%-22.8%).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P>0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P>0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.
8.The impact of programming optimization for atrioventricular synchrony after Micra AV leadless pacemakers implantation
Ze ZHENG ; Yu-Chen SHI ; Song-Yuan HE ; Shao-Ping WANG ; Shi-Ying LI ; Shu-Juan CHENG ; Jing-Hua LIU
Chinese Journal of Interventional Cardiology 2024;32(2):71-75
Objective To analyze the atrioventricular synchronization rate after implantation of Micra AV leadless pacemaker,and the impact of postoperative programming optimization on atrioventricular synchronization rate.Methods A prospective cohort study was conducted to select patients with complete atrioventricular block who underwent Micra AV leadless pacemaker implantation at Beijing Anzhen Hospital from August 2022 to June 2023.Programming optimization were performed at 1 week,1 month,and 3 months postoperatively,and atrioventricular synchronization rate,electrical parameters,and echocardiography were recorded.Results A total of 68 patients with complete atrioventricular block implanted with Micra AV were selected,with an average age of(68.2±9.7)years,including 47 males(69.1%).All patients were successfully implanted with Micra AV,and there were no serious postoperative complications;The average threshold,sense,and impedance parameters were stable during 1 week,1 month,and 3 months after the procedure;There was no significant difference in the EF value of postoperative echocardiography(P=0.162);The average atrioventricular synchronization rates at 1 week,1 month,and 3 months postoperatively were(75.2%vs.83.8%vs.91.6%,P=0.001).Conclusions As an mechanical atrial sensing,Micra AV requires personalized adjustment of relevant parameters;Postoperative follow-up programming optimization plays an important role in the atrioventricular synchronization and comfort level in patients with complete atrioventricular block after implantation of Micra AV leadless pacemaker.
9.Research status in immunotherapy of colitis-related cancer with MDSCs
Jia CHEN ; Qi XIA ; Yu-Jie HE ; Yue LI ; Ze-Ting YUAN ; Pei-Hao YIN
The Chinese Journal of Clinical Pharmacology 2024;40(2):294-298
Colitis-associated cancer(CAC)is a specific type of colorectal cancer that develops from inflammatory bowel disease(IBD).Myeloid-derived suppressor cells(MDSCs)are a group of myeloid cells with immunosuppressive properties,and MDSCs in the tumor microenvironment proliferate and activate during the development of colitis-associated cancer,inhibiting T-cell production and impairing their function,which impedes the immunotherapeutic effect of colitis-associated cancer.In this paper,we review the immunosuppressive mechanisms of MDSCs in the development of inflammatory bowel disease to colitis-associated cancers and the current drugs targeting MDSCs for immunotherapy of inflammatory colorectal cancers,with a view to providing new strategies for the treatment of colitis-associated cancers.
10.Effects of cinbufagin on proliferation,migration and invasion of human colon cancer cells via JAK2/STAT3 pathway
Jia CHEN ; Qi XIA ; Yi-Nan LI ; Yu-Jie HE ; Ze-Ting YUAN ; Yue LI ; Pei-Hao YIN
The Chinese Journal of Clinical Pharmacology 2024;40(12):1764-1768
Objective To investigate the effects of cinbufagin(CB)on the proliferation,migration and invasion ability as well as epithelial-mesenchymal transition(EMT)of human colon cells HCT116.Methods Logarithmically grown HCT116 cells were randomly divided into blank group and experimental-L,-M,-H groups;the blank group did not receive any treatment(0 nmol·L-1),and experimental-L,-M,-H groups were cultured in 1 640 medium containing 17.5,35 and 70 nmol·L-1 cinbufagin for 48 h.Cell counting kit-8(CCK-8)was used to detect the effect of cinbufagin on the survival rate of HCT116 cells;cloning assay was used to detect the effect of cinbufagin on the proliferation of HCT116 cells;cell scratch assay and Transwell assay were used to detect the effect of cinbufagin on the migration and invasive ability of HCT116 cells;Western blot was used to detect the expression levels of janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)pathway and EMT-related proteins of HCT116 cells.Results The number of clone formation in blank group and experimental-L,-M,-H groups were 122.67±24.42,73.67±15.82,44.33±4.51 and 21.67±1.53;the rates of migration of scratches were(44.64±9.15)%,(26.91±2.94)%,(19.28±1.52)%and(6.33±2.30)%;the number of invaded cells were 120.33±1.15,58.33±9.07,33.33±1.53 and 18.33±3.21;the relative protein expression of phosphorylated JAK-2(p-JAK-2)/JAK-2 were 1.02±0.06,0.94±0.05,0.75±0.22 and 0.49±0.22;relative protein expression of phosphorylated STAT3(p-STAT3)/STAT3 were 0.89±0.10,0.72±0.04,0.65±0.06 and 0.52±0.18;relative protein expression of E-cadherin were 0.30±0.14,0.41±0.13,0.49±0.14 and 0.69±0.17;relative protein expression of N-cadherin were 0.96±0.11,0.78±0.04,0.69±0.12 and 0.40±0.15;Snail relative protein expression were 0.89±0.08,0.62±0.15,0.44±0.15 and 0.27±0.09;Vimentin relative protein expression were 0.92±0.09,0.76±0.13,0.63±0.01 and 0.43±0.09,respectively.The above indexes in experimental-H group showed statistically significant differences compared to blank group(all P<0.05).Conclusion HCT116 can inhibit the invasion and metastasis of human colorectal cancer cells HCT116 by inhibiting epithelial-mesenchymal transition through JAK2/STAT3 pathway.

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