1.Establishment and assessment of deep vein thrombosis model in rats in a plateau hypoxic environment
Xiaobo HAN ; Yahao CHAI ; Jiawei GAO ; Xinkai DENG ; Xiao LI ; Jialin WU ; Xiaoli HAN ; Guoxiang LI ; Yinjie ZHAO ; Xi YANG ; Qi AO ; Lei ZHANG ; Hongwei HAN ; Zhixue LIU
Acta Laboratorium Animalis Scientia Sinica 2025;33(8):1133-1143
Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P<0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P<0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.
2.Establishment and assessment of deep vein thrombosis model in rats in a plateau hypoxic environment
Xiaobo HAN ; Yahao CHAI ; Jiawei GAO ; Xinkai DENG ; Xiao LI ; Jialin WU ; Xiaoli HAN ; Guoxiang LI ; Yinjie ZHAO ; Xi YANG ; Qi AO ; Lei ZHANG ; Hongwei HAN ; Zhixue LIU
Acta Laboratorium Animalis Scientia Sinica 2025;33(8):1133-1143
Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P<0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P<0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.
3.Development and preliminary clinical evaluation of an optical digital border molding technique for soft tissue movement boundary in edentulous jaws
Xinkai XU ; Kehui DENG ; Sukun TIAN ; Hu CHEN ; Weiwei LI ; Xing SU ; Xiaobo ZHAO ; Xiaojun CHEN ; Chao MA ; Yongjie JIA ; Shujuan XIAO ; Yuchun SUN
Chinese Journal of Stomatology 2025;60(6):611-617
Objective:To address the critical issue of missing dynamic border molding information in edentulous direct digital impression technology, this study explores innovative digital solutions and conducts preliminary application validation.Methods:Based on the myostatic line theory, a methodology was established: intraoral scanner (IOS) high-frequency video was utilized to dynamically capture functional molding data of soft tissues, integrated with a self-developed mobility gradient recognition algorithm to achieve dynamic threshold segmentation between the muscle dynamic zone and myostatic zone, termed "optical digital molding technology". Ten edentulous patients with well-fitting complete dentures, treated at the Department of Prosthodontics, Peking University School and Hospital of Stomatology from January 2024 to December 2024, were enrolled. The standard deviation between the muscle static line (generated by mobility gradient algorithm with thresholds of 0.3-0.7 mm) and the denture border curve was analyzed to optimize the dynamic threshold, followed by single-case clinical validation.Results:Among the mobility thresholds of 0.3-0.7 mm, the 0.5 mm threshold yielded the smallest standard deviation between the myostatic line and denture border. Clinical validation demonstrated that dentures designed with this threshold exhibited no displacement during dynamic functional tests, with marginal sealing meeting clinical standards.Conclusions:The optical digital border molding technique for edentulous soft tissue boundaries translates the myostatic line theory into quantifiable parameters for the first time. Based on data from 10 cases, a mobility threshold of 0.5 mm is recommended for clinical application.
4.Correlation analysis of RNFT2,MFAP2,and AFF3 expression with tumor pathological features and prognosis in gastric cancer patients
Zhuang CHEN ; Xinkai ZHAO ; Wenjun WANG ; Shanshan QIU
Journal of Clinical Surgery 2025;33(2):144-148
Objective To investigate the expression of RNFT2,MFAP2,and AF4/FMR2 family member 3(AFF3)in gastric cancer(GC)tissues,and to analyze their correlation with tumor pathological features and prognosis.Methods GC tissue specimens and adjacent tissue specimens were collected from 98 GC patients who underwent surgery in our hospital from May 2018 to January 2020,clinical data were also collected.Immunohistochemical methods were applied to detect the expression of RNFT2,MFAP2,and AFF3;Kaplan-Meier method was applied to analyze the relationship between the expression of RNFT2,MFAP2,and AFF3 and the prognosis of GC patients;multivariate Cox regression was applied to analyze the influencing factors of prognosis in GC patients.Results Compared with adjacent tissues,the positive rates of RNFT2 and MFAP2 proteins in GC tissue were obviously higher(75.51%vs.29.59%,70.41%vs.19.39%),while the positive rate of AFF3 protein was obviously lower(26.53%vs.68.37%,P<0.05).The expression of RNFT2,MFAP2,and AFF3 proteins was obviously corr-elated with TNM staging and differentiation degree(P<0.05);Kaplan-Meier method showed that the 3-year survival rates of RNFT2 and MFAP2 positive expression patients were lower than those of RNFT2 and MFAP2 negative expression patients,respectively,the 3-year survival rate of AFF3 positive expression patients was higher than that of AFF3 negative expression patients(P<0.05).Multivariate Cox regression analysis showed that RNFT2,MFAP2,AFF3,TNM staging,and differentiation degree were prognostic factors for GC patients.Conclusion RNFT2 and MFAP2 are obviously upregulated in GC tissue,while AFF3 is obviously downregulated,which is closely related to clinical pathological features(such as TNM staging and differentiation)and prognosis,and has important value for the prognosis and survival of GC patients.
5.Cost-effectiveness of angiographic quantitative flow ratio-guided coronary intervention: A multicenter, randomized, sham-controlled trial.
Yanyan ZHAO ; Changdong GUAN ; Yang WANG ; Zening JIN ; Bo YU ; Guosheng FU ; Yundai CHEN ; Lijun GUO ; Xinkai QU ; Yaojun ZHANG ; Kefei DOU ; Yongjian WU ; Weixian YANG ; Shengxian TU ; Javier ESCANED ; William F FEARON ; Shubin QIAO ; David J COHEN ; Harlan M KRUMHOLZ ; Bo XU ; Lei SONG
Chinese Medical Journal 2025;138(10):1186-1193
BACKGROUND:
The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system.
METHODS:
This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China.
RESULTS:
At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained.
CONCLUSION:
In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system.
TRIAL REGISTRATION
ClinicalTrials.gov , NCT03656848.
Humans
;
Cost-Benefit Analysis
;
Percutaneous Coronary Intervention/methods*
;
Male
;
Female
;
Coronary Angiography/methods*
;
Middle Aged
;
Aged
;
Coronary Artery Disease/surgery*
;
Quality-Adjusted Life Years
;
Fractional Flow Reserve, Myocardial/physiology*
6.Correlation analysis of RNFT2,MFAP2,and AFF3 expression with tumor pathological features and prognosis in gastric cancer patients
Zhuang CHEN ; Xinkai ZHAO ; Wenjun WANG ; Shanshan QIU
Journal of Clinical Surgery 2025;33(2):144-148
Objective To investigate the expression of RNFT2,MFAP2,and AF4/FMR2 family member 3(AFF3)in gastric cancer(GC)tissues,and to analyze their correlation with tumor pathological features and prognosis.Methods GC tissue specimens and adjacent tissue specimens were collected from 98 GC patients who underwent surgery in our hospital from May 2018 to January 2020,clinical data were also collected.Immunohistochemical methods were applied to detect the expression of RNFT2,MFAP2,and AFF3;Kaplan-Meier method was applied to analyze the relationship between the expression of RNFT2,MFAP2,and AFF3 and the prognosis of GC patients;multivariate Cox regression was applied to analyze the influencing factors of prognosis in GC patients.Results Compared with adjacent tissues,the positive rates of RNFT2 and MFAP2 proteins in GC tissue were obviously higher(75.51%vs.29.59%,70.41%vs.19.39%),while the positive rate of AFF3 protein was obviously lower(26.53%vs.68.37%,P<0.05).The expression of RNFT2,MFAP2,and AFF3 proteins was obviously corr-elated with TNM staging and differentiation degree(P<0.05);Kaplan-Meier method showed that the 3-year survival rates of RNFT2 and MFAP2 positive expression patients were lower than those of RNFT2 and MFAP2 negative expression patients,respectively,the 3-year survival rate of AFF3 positive expression patients was higher than that of AFF3 negative expression patients(P<0.05).Multivariate Cox regression analysis showed that RNFT2,MFAP2,AFF3,TNM staging,and differentiation degree were prognostic factors for GC patients.Conclusion RNFT2 and MFAP2 are obviously upregulated in GC tissue,while AFF3 is obviously downregulated,which is closely related to clinical pathological features(such as TNM staging and differentiation)and prognosis,and has important value for the prognosis and survival of GC patients.
7.Development and preliminary clinical evaluation of an optical digital border molding technique for soft tissue movement boundary in edentulous jaws
Xinkai XU ; Kehui DENG ; Sukun TIAN ; Hu CHEN ; Weiwei LI ; Xing SU ; Xiaobo ZHAO ; Xiaojun CHEN ; Chao MA ; Yongjie JIA ; Shujuan XIAO ; Yuchun SUN
Chinese Journal of Stomatology 2025;60(6):611-617
Objective:To address the critical issue of missing dynamic border molding information in edentulous direct digital impression technology, this study explores innovative digital solutions and conducts preliminary application validation.Methods:Based on the myostatic line theory, a methodology was established: intraoral scanner (IOS) high-frequency video was utilized to dynamically capture functional molding data of soft tissues, integrated with a self-developed mobility gradient recognition algorithm to achieve dynamic threshold segmentation between the muscle dynamic zone and myostatic zone, termed "optical digital molding technology". Ten edentulous patients with well-fitting complete dentures, treated at the Department of Prosthodontics, Peking University School and Hospital of Stomatology from January 2024 to December 2024, were enrolled. The standard deviation between the muscle static line (generated by mobility gradient algorithm with thresholds of 0.3-0.7 mm) and the denture border curve was analyzed to optimize the dynamic threshold, followed by single-case clinical validation.Results:Among the mobility thresholds of 0.3-0.7 mm, the 0.5 mm threshold yielded the smallest standard deviation between the myostatic line and denture border. Clinical validation demonstrated that dentures designed with this threshold exhibited no displacement during dynamic functional tests, with marginal sealing meeting clinical standards.Conclusions:The optical digital border molding technique for edentulous soft tissue boundaries translates the myostatic line theory into quantifiable parameters for the first time. Based on data from 10 cases, a mobility threshold of 0.5 mm is recommended for clinical application.
8.Evaluation of the accuracy of three-dimensional data acquisition from liquid-inter-ference surfaces assisted by a scanner head with a compressed airflow system
Xinkai XU ; Jianjiang ZHAO ; Sukun TIAN ; Zhongning LIU ; Xiaoyi ZHAO ; Xiaobo ZHAO ; Tengfei JIANG ; Xiaojun CHEN ; Chao MA ; Yuchun SUN
Journal of Peking University(Health Sciences) 2025;57(1):121-127
Objective:To quantitatively evaluate the accuracy of data obtained from liquid-interference surfaces using an intraoral 3D scanner(IOS)integrated with a compressed airflow system,so as to pro-vide clinical proof of accuracy for the application of the compressed airflow system-based scanning head in improving data quality on liquid-interference surfaces.Methods:The study selected a standard model as the scanning object,adhering to the"YY/T 1818-2022 Dental Science Intraoral Digital Impression Scanner"guidelines,a standard that defined parameters for intraoral scanning.To establish a baseline for accuracy,the ATOS Q 12M scanner,known for its high precision,was used to generate true reference values.These true values served as the benchmark for evaluating the IOS performance.Building on the design of an existing scanner,a new scanning head was developed to integrate with a compressed airflow system.This new design aimed to help the IOS capture high-precision data on sur-faces where liquid-interference,such as saliva,might otherwise degrade scanning accuracy.The tradi-tional scanning method,without airflow assistance,was employed as a control group for comparison.The study included five groups in total,one control group and four experimental groups,to investigate the effects of scanning lens obstruction,airflow presence,liquid media,and the use of the new scan-ning head on scanning process and accuracy.Each group underwent 15 scans,generating ample data for a robust statistical comparison.By evaluating trueness and precision in each group,the study as-sessed the impact of the compressed airflow system on the accuracy of IOS data collected from liquid-interference surfaces.Additionally,we selected Elite and Primescan scanners as references for numeri-cal accuracy values.Results:The scanning accuracy on liquid-interference surfaces was significantly reduced in terms of both trueness and precision[Trueness:18.5(6.5)vs.38.0(6.7),P<0.05;Preci-sion:19.1(8.5)vs.31.7(15.0),P<0.05].The use of the new scanning head assisted by the com-pressed airflow system significantly improved the scanning accuracy[Trueness:22.3(7.6)vs.38.0(6.7),P<0.05;Precision:25.8(9.6)vs.31.7(15.0),P<0.05].Conclusion:The scanning head based on the compressed airflow system can assist in improving the accuracy of data obtained from liquid-inter-ference surfaces by the IOS.
9.Establishment of a New Hyperglycemic Obesity Cardiac Dysfunction Mouse Model with Triacsin C
Xiaona ZHAO ; Peng WANG ; Maoqing YE ; Xinkai QU
Laboratory Animal and Comparative Medicine 2024;44(6):605-612
Objective This study aims to establish a novel hyperglycemic obesity mouse model by utilizing Triacsin C, an inhibitor of acyl-CoA synthetase long-chain family member 1 (ACSL1), combined with a high-fat diet, to simulate the changes in adipose tissue and cardiac function observed in patients with obesity-related type 2 diabetes. MethodsTwenty adult SPF-grade male C57BL/6J mice were randomly divided into two groups: the Control group (injected intraperitoneally with citric acid-sodium citrate buffer, Con group) and the TC group (injected intraperitoneally with Triacsin C, TC group). After four consecutive weeks of intraperitoneal injections, both groups were fed high-fat diets. Body weight and glucose tolerance of the mice were assessed every eight weeks. The models were considered successful if fasting blood glucose exceeded 8 mmol/L or blood glucose was above 15 mmol/L two hours after glucose injection. Cardiac function, including ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), end-diastolic interventricular septal thickness (EDIVS), left ventricular ejection fraction (LVEF), and left ventricular short-axis fractional shortening (FS), was measured by echocardiography. HE staining was used to detect the changes in epididymal white adipose tissue (WAT) and brown adipose tissue (BAT). Immunofluorescence technology was used to analyze changes in CD31 and UCP1 in BAT. ACSL1 expression in myocardial tissue was tested by Western blotting. ResultsThe fasting blood glucose levels were (8.14±1.43) mmol/L in the Con group and (8.18±0.85) mmol/L in the TC group (P>0.05) , and the 2-hour postprandial blood glucose levels were (19.8±4.01) mmol/L in the Con group and (22.60±3.97) mmol/L in the TC group (P<0.05). This indicated that both groups of diabetic mouse models were successfully established. Compared to the Con group, the TC group showed poor glucose tolerance; significant decreases in LVEDD, LVEF and FS (P<0.05); significant increases in WAT and BAT areas (P<0.05); significant decreases in CD31 and UCP1 expression (P<0.05); and a significant decrease in the expression of ACSL1 in myocardial tissues (P<0.05). ConclusionCompared with the high-fat diet-induced type 2 diabetes model, the new hyperglycemic obesity and cardiac dysfunction mouse model, created by the combination of Triacsin C and a high-fat diet, is feasible and allows for easier observation of brown adipose tissue whitening, insulin resistance and cardiac dysfunction.
10.Effect and mechanism of targeted delivery of VEGF and CD47 dual-modifiedexosomes in treatment of acute kidney injury induced by heat stroke in rats in the desert dry hot environment.
Xiaobo HAN ; Xinkai DENG ; Hong LI ; Chao LIU ; Jiawei GAO ; Xiao LI ; Yahao CHAI ; Xiaoli HAN ; Hongwei HAN ; Yinjie ZHAO ; Xi YANG ; Lei ZHANG
Journal of Army Medical University 2024;46(18):2057-2068
Objective To develop an effective method for delivering VEGF and CD47 double-modified exosomes to treat renal damage induced by heat stroke so as to reduce and repair renal damage.Methods A plasmid fusion-expressing VEGF and CD47 targeting renal injury was constructed,transfected into rat bone marrow derived mesenchymal stem cells (BMMSCs),and then fusion-exosomes were isolated and extracted.Transmission electron microscopy,nanoparticle tracking analysis,and Western blotting were used to identify the obtained exosomes.Rats were intravenously injected with 200 μg of DiD-labeled unmodified exosomes,VEGF-modified exosomes and VEGF-CD47 double-modified exosomes,respectively,through the tail vein,and the effects of exosomes on the kidneys were detected and analyzed using a small animal in vivo imaging instrument.A total of 60 SD rats were randomly divided into 6 groups,with 10 rats in each group,that is,blank control group (group A),heat stroke-induced renal injury model receiving PBS in 12,24 and 36 h after modelling (group B),empty plasmid group (group C),Exos group (group D),ExosVEGF group (group E) and ExosVEGF-CD47.Kidney tissue and blood samples were collected in 72 h after 3 times of treatment.Pathological changes in kidney tissue were observed at the tissue level and the damage were scored.Changes in serum blood urea nitrogen (BUN)and serum creatinine (Scr)levels were detected to evaluate the therapeutic effect.Western blotting and qRT-PCR were used to analyze the expression of the pro-inflammatory factors TNF-α and NF-κB,the proliferation regulatory signaling molecules Ki67,FGF2,pAMPK and pERK,and the fibrosis regulatory molecule FGF23,in order to comprehensively analyze the effects on proliferation and inhibition of fibrosis.Results BMMSCs and ExosVEGF-CD47 were successfully isolated and characterized,and a rat model of acute kidney injury was effectively constructed.Higher fluorescence intensity was found in the kidney tissue of the Exos VEGF-CD47group than the Exos-Ctrl group and Exos VEGF group (P<0.05).In 72 h after treatment,the ExosVEGF-CD47 group had significantly lower serum BUN and Scr levels (P<0.0001),and notably lower Tubular casts score (P<0.0001),decreased levels of pro-inflammatory factors TNF-α and NF-κB (P<0.0001),up-regulated Ki67 and FGF2 expression (P<0.05),and down-regulated FGF23 expression (P<0.0001)when compared with the AKI+Exos group and AKI+ExosVEGF group.Conclusion VEGF and CD47 show promise in targeting acute kidney injury induced by heat stroke,effectively mitigate damage and facilitate repair,which may be due to exosome-mediated inhibition of renal tissue inflammation,promotion of proliferation,and inhibition of fibrosis.

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