1.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.
2.Efficacy and Safety of Polatuzumab Vedotin Combined with Chemotherapy in the Treatment of Relapsed and Refractory Diffuse Large B-Cell Lymphoma
Ke-Ting JIN ; Jin-Dan XIA ; Chu-Yun QIAN ; Qian ZHANG ; Qian JIANG ; Song-Di CHEN ; Wei-Ze ZHANG ; Lu-Ling MAO ; Yi ZHAO
Journal of Experimental Hematology 2025;33(6):1617-1622
Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.
3.Analysis of Neurological Complications and Related Risk Factors After Left Ventricular Assist Device Implantation
Haotian ZHANG ; Xingtong ZHOU ; Zelin YIN ; Juan DU ; Fengqing ZHANG ; Haibo CHEN ; Ping QING ; Xiaohu WANG ; Ze ZHANG ; Liang ZOU ; Yi CHEN ; Yan JIN ; Xianqiang WANG
Chinese Circulation Journal 2025;40(4):359-366
Objectives:To evaluate the incidence of neurological complications following left ventricular assist device(LVAD)implantation and to investigate related risk factors.Methods:A retrospective analysis was conducted on 151 patients who underwent LVAD implantation at Fuwai Hospital between June 2017 and September 2024.Clinical characteristics and postoperative survival outcomes were compared between patients with and without neurological complications.Results:Neurological complications occurred in 21 patients(13.9%)postoperatively,15 cases were ischemic strokes,5 cases were symptomatic intracranial hemorrhages or subarachnoid hemorrhages,and 1 case was transient ischemic attack(TIA).The total incidence of neurological complications was 0.08 events per person-year(EPPY),ischemic stroke was 0.06 EPPY and hemorrhagic stroke was 0.02 EPPY.Compared with patients without neurological complications,patients with neurological complications had a higher proportion of preoperative aortic regurgitation and tricuspid regurgitation,lower triglyceride levels,a lower rate of concurrent left atrial appendage resection and a higher rate of concurrent aortic valve replacement surgery.Multivariate cox regression analysis revealed that higher preoperative triglyceride levels(HR=0.21,95%CI:0.08-0.56,P=0.002)were associated with neurological complications.The median follow-up time was 508.0(186.5,931.5)days,12 out of 15 cases of ischemic stroke experienced no long-term sequelae,while 3 patients had varying degrees of residual deficits.All 5 patients with hemorrhagic stroke died,with 2 deaths directly attributed to hemorrhage.Kaplan-Meier survival curve analysis indicated that patients with neurological complications had a significantly lower survival rate(log-rank P=0.005).Conclusions:Neurological complications after LVAD implantation are predominantly ischemic strokes.Although less frequent,hemorrhagic strokes are associated with worse outcomes.Higher preoperative triglyceride levels is associated with neurological complications.
4.Effect of Draxin on the migration characteristics of trunk neural crest cells in the embryonic mouse spinal cord
Zu-Qi CUI ; Xiao-Jin MIAO ; Ze-Lin GU ; Meng-Fei GONG ; Huan CHEN ; Shu-Han YANG ; Tong-Yu LIU ; San-Bing ZHANG ; Yu-Hong SU
Acta Anatomica Sinica 2025;56(2):150-157
Objective To investigate the effect of dorsal repulsive axon guidance protein(Draxin)on the migration of trunk neural crest cells during the early development of embryonic mouse spinal cord.Methods Immunohistochemistry and in situ hybridization were used to detect the expression characteristics of Draxin in early embryonic spinal cord(8 mice each group);In situ hybridization was used to detect the change of migration characteristics of trunk neural crest cells in early embryonic spinal cord of different types of mouse(5 mice each group);in vitro culture method was used to check the effect of Draxin on the migration characteristics of embryonic mouse trunk neural crest cells(16 mice each group).Resultsβ-galactosidase gene Z(LacZ)gene was introduced when Draxin gene was knocked out to produce Draxin gene knockout mice.β-galactosidase staining was used to detect LacZ gene expression in Draxin knockout embryonic mice,and the result showed that Draxin expression was observed in the spinal cord of early embryonic mice since 9.5 days(E9.5).Draxin expression was obvious in the embryonic mice spinal cord in E10.5 period.In situ hybridization was used to detect the expression of Draxin gene in the spinal cord of wild type embryonic mice,and the result further verified the obvious expression of Draxin in the early embryonic mice spinal cord in El0.5 period.Sox10 in situ hybridization was used to detect neural crest cell migration in the spinal cord of embryonic mice in E10.5 period.The result showed that segmental migration of neural crest cells in the early embryonic spinal cord of some Draxin knockout mice was delayed compared with the wild type mice.The effect of Draxin on the migration of wild type early embryonic mice trunk neural crest cells in vitro was tested.The result showed that Draxin reduced the migration distance of neural crest cells in vitro.Conclusion In the early developmental stage of embryonic spinal cord(E9.5-E10.5),neural crest cells migrated exuberant.At the same time,Draxin plays an important inhibitory function in the formation of the specific migration pathways of trunk neural crest cells by promoting neural crest cells migrating away from Draxin expressing regions.
5.Effect of different layers of masseter on the bony structure of facial lateral area
Yu-Qi ZHAO ; Jin-Rui JIANG ; Jin-Ran CHEN ; Ze-Chuan WANG ; Hou-En ZHOU ; Wen-Di XU ; Liu-Jun YONG
Acta Anatomica Sinica 2025;56(2):208-213
Objective To observe the morphology of the superficial,middle,and deep layers of the masseter muscle and related bony structures in the lateral facial region of adults through gross anatomy,and to probe into the effects of these muscle layers on the bony structures of the lateral facial region.Methods The bilateral masseter muscles of 12 adult cadavers were exposed,and the superficial,middle,and deep layers were separated and measured for muscle length,tendon length,and muscle belly length.After the masseter muscles were stripped,the total thickness was measured,and the mandible and zygomatic arch were exposed to measure the angle of the mandibular angle,thickness of the zygomatic arch,and width of the zygomatic arch.Observations were made of the masseter tuberosities,and statistical analysis was conducted on their interrelations.Results The zygomatic arch thickness was positively correlated with the length of superficial,middle and deep masseter muscles and the length of superficial and middle masseter belly(r superficial masseter length=0.624,r middle masseter length=0.787,r deep masseter length=0.423,r superficial masseter belly length=0.493,r middle masseter belly length=0.548).The width of the zygomatic arch was positively correlated with the lengths of the superficial and middle muscle layers and the middle muscle belly length(r superficial masseter length=0.527,r middle masseter length=0.521,r middle masseterbelly length=0.437).The angle of the mandibular angle was only negatively correlated with the middle muscle belly length(r=-0.422).The tuberosities of the superficial and middle masseter muscles were not affected by the corresponding muscle layers;However,the tuberosity of the deep masseter was negatively correlated with the length of the deep muscle and the length of the deep tendon(r deep masseter length=-0.543,r deep masseter tendon length=-0.443).Conclusion In the masseter muscle layers of Chinese individuals,the superficial and middle layers have the most significant impact on the bony structures structures of the lateral facial region.These findings are of guiding significance for the remodeling of structures in the lateral facial region.
6.The impact of medical insurance payment reform on medical services and costs:A case study of Jinhua
Miao YU ; Ze-yao LI ; Hong-wu TUO ; Yan-sui YANG ; Guan-pin WU ; Hua-qiang JIN ; Xiao-zhou JIANG
Chinese Journal of Health Policy 2025;18(1):43-50
Objective:This study empirically analyzes the relationship between outpatient and inpatient services under the impact of healthcare payment reform,and evaluates the effects of the reform.Methods:Data from healthcare services and basic medical insurance payments in eight districts of Jinhua City from 2020 to 2022 were used.A fixed-effects model for outpatient and inpatient services was constructed to analyze the impact of healthcare payment reforms and outpatient services on inpatient services.Results:The DRG-based payment had a significant positive effect on inpatient visits and a significant negative effect on employee basic medical insurance inpatient costs.The"capitation+APG"outpatient payment policy had a significant negative effect on inpatient visits and a significant negative effect on residents'basic medical insurance inpatient costs.The interaction between outpatient payment and outpatient visits had a significant negative effect on employee basic medical insurance inpatient visits,while the interaction between outpatient payment and outpatient costs had a significant negative effect on both overall and employee inpatient costs.Conclusions:The DRG payment reform led to an increase in inpatient visits and a reduction in employee basic medical insurance inpatient costs.The outpatient"capitation+APG"payment reform reduced inpatient visits and lowered residents'basic medical insurance inpatient costs,thereby slowing down the complementary effect between outpatient and inpatient services.
7.Construction of Human-derived Chondrocyte PIEZO2 Overexpressing Cell Line and Identification of Osteoarthritis Phenotype
Bo-Yang XU ; Yi-Fei FAN ; Yu-Qing DU ; Meng-Ze SUN ; Jun-Yan WANG ; Jin CHENG ; Ying-Fang AO ; Xiao-Qing HU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):871-878
To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49%).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50%of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10%strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.
8.OBE-based Design of Biochemistry Teaching:Taking the Teaching of"Classification and Specificity of Enzymes"as an Example
Hua HAI ; Li-Yan NA ; Ming-Lei HE ; Hong-Ze YANG ; Li-Ming JIN ; Chun-Bin LI ; Hua JIN ; Quan ZHOU ; De-Fu ZHI
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):903-913
Biochemistry,as a fundamental course for science and engineering majors related to biology and chemistry,holds a significant position in the curriculum.The course team at Dalian Minzu University is committed to teaching innovation,adopting the outcome-based education(OBE)concept for teaching de-sign and incorporating ideological and political elements,in order to achieve the dual goals of knowledge transmission and value guidance.The team has established a three-dimensional teaching goal of"knowl-edge,morality,and ability",covering"consolidating core knowledge,cultivating moral sentiment,and enhancing innovation ability".Through a multi-dimensional integrated teaching method of"three integra-tions and five combinations",multiple rounds of teaching practice have been carried out in the applied chemistry major using"classification and specificity of enzyme"as an example.The output of teaching re-sults and survey questionnaires show that students highly recognize the teaching design and its"process-based learning"evaluation method,fully reflecting the student-centered teaching idea.Research has shown that OBE design combined with ideological and political elements can effectively promote students' knowl-edge acquisition,moral growth,and innovation ability improvement in the course of Biochemistry.This teaching design not only helps students construct correct worldviews,outlooks on life,and values,but also significantly enhances their innovative thinking and practical abilities.This teaching design can not only ef-fectively improve the teaching quality of the course,but also provide new perspectives and ideas for the teaching design of Biochemistry,realizing the organic integration of professional knowledge imparting and i-deological and political education,and has certain innovation and practical significance.
9.Clinical analysis of splenic circulation control technology applied in minimally invasive radical resection of pancreatic neck and body cancer
Qicong ZHU ; Ze JIN ; Weiwei JIN ; Yiping MOU ; Yucheng ZHOU ; Chao LU
Chinese Journal of Surgery 2025;63(8):727-731
Objective:To evaluate the effectiveness of splenic circulation control technology in minimally invasive radical resection surgery for pancreatic neck/body cancer.Methods:This is a retrospective case series study. Retrospective analysis of clinical data of 12 patients who underwent laparoscopic or robotic radical resection for pancreatic neck/body cancer at the Department of Gastrointestinal and Pancreatic Surgery,Zhejiang Provincial People′s Hospital between January 2024 and January 2025. There were 7 males and 5 females,with mean age of 68 years (range: 52 to 79 years). Clinical data including preoperative,intra-operative and postoperative outcomes were analyzed. Postoperative follow-up was conducted via outpatient visits and telephone interviews,with the follow-up ending on April 1,2025.Results:All 12 patients underwent minimally invasive radical resection of pancreatic neck/body cancer using splenic circulation control technology,consisted of 3 laparoscopic and 9 robotic procedures. The mean operative time was 185 minutes (range: 140 to 315 minutes),and the average blood loss was 100 ml (range: 30 to 300 ml). Two cases involved combined organ resection.There was no conversion to open surgery. Postoperative complications were observed in 2 patients. One patient developed grade B pancreatic leakage,managed by ultrasound-guided puncture.The patient was discharged with drainage tube. The other patient experienced chylous leakage,recovered with conservative treatment. No delayed gastric emptying,hemorrhage or reoperations were observed. The median postoperative hospital stay was 13 days (range: 8 to 20 days).Conclusion:The splenic circulation control technique is simple and safe,and shows certain application prospects in minimally invasive radical resection of pancreatic neck and body cancer.
10.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.

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