1.Erratum: Author correction to "Generation of αGal-enhanced bifunctional tumor vaccine" Acta Pharm Sin B 12 (2022) 3177-3186.
Jian HE ; Yu HUO ; Zhikun ZHANG ; Yiqun LUO ; Xiuli LIU ; Qiaoying CHEN ; Pan WU ; Wei SHI ; Tao WU ; Chao TANG ; Huixue WANG ; Lan LI ; Xiyu LIU ; Yong HUANG ; Yongxiang ZHAO ; Lu GAN ; Bing WANG ; Liping ZHONG
Acta Pharmaceutica Sinica B 2025;15(2):1207-1207
[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].
2.Exercise preconditioning combined with bone marrow mesenchymal stem cell transplantation for myocardial infarction in rats
Zhikun WANG ; Shaoxuan BAI ; Wei ZHAO ; Chenyu WANG
Chinese Journal of Tissue Engineering Research 2025;29(1):65-73
BACKGROUND:Stem cell therapy has broad prospects in improving cardiac remodeling after myocardial infarction;however,alteration in the myocardial microenvironment affects the therapeutic efficacy of stem cells.Exercise preconditioning is similar to ischemic preconditioning and can have a protective effect on the myocardium.However,little attention has been paid to the effects and mechanisms of the combined effects of exercise preconditioning and stem cell transplantation. OBJECTIVE:To observe the effect of exercise preconditioning on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction and to explore the mechanism of local inflammatory microenvironment. METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group,and combination group,with 20 rats in each group.The rat model of myocardial infarction was made by ligating the left anterior descending branch of coronary artery.The sham operation group was only threaded without ligature.The transplantation and combination groups were injected with bone marrow mesenchymal stem cells of male rats into the myocardium after modeling.In addition,the combination group also required 8 weeks of treadmill exercise(i.e.,exercise preconditioning)before modeling.Four weeks after stem cell transplantation,exercise performance was measured by incremental exercise exhaustion test;cardiac structure and function were measured by echocardiography;left ventricular hemodynamics was measured by pressure-volume catheterization,and myocardial histopathology was observed by in situ staining and myocardial collagen volume fraction was obtained.Quantitative reverse transcription polymerase chain reaction was used to detect left ventricular pro-inflammatory factor(interleukin-1β,interleukin-6,tumor necrosis factor-α),anti-inflammatory factor(interleukin-10),sex-determining region of Y chromosome,and fetal genes(atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain)mRNA expression level at 1,7 days and 4 weeks after stem cell transplantation. RESULTS AND CONCLUSION:(1)Four weeks after stem cell transplantation:compared with sham operation group,exercise performance,and left ventricular ejection fraction were reduced(P<0.05);myocardial infarction area,cardiomyocyte cross-sectional area,and collagen volume fraction were increased(P<0.05);the mRNA expression of fetal genes and pro-inflammatory factors were up-regulated(P<0.05),and the mRNA expression of interleukin-10 was down-regulated(P<0.05)in the model group.Compared with the model group,exercise performance and left ventricular ejection fraction were increased(P<0.05);myocardial infarction area,cardiomyocyte cross-sectional area,and collagen volume fraction were decreased(P<0.05);mRNA expression of fetal genes and pro-inflammatory factors was down-regulated(P<0.05),and that of interleukin-10 had no significant change(P>0.05)in the transplantation group.Compared with the transplantation group,all the above indicators in the combination group were further improved(P<0.05).(2)One day and 7 days after stem cell transplantation,compared with the transplantation group,the mRNA expression of sex-determining region of Y chromosome in the combination group increased(P<0.05).(3)Correlation analysis showed that interleukin-1β,interleukin-6(except on the 1st day after transplantation),and tumor necrosis factor-α were negatively correlated with the mRNA expression of sex-determining region of Y chromosome(P<0.05),while interleukin-10 was positively correlated with that of sex-determining region of Y chromosome(P<0.05).These findings suggest that exercise preconditioning can enhance the effect of bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction,which is characterized by suppression of cardiac remodeling and further amelioration of cardiac function.The mechanism is related to the improvement of the myocardial inflammatory microenvironment to promote bone marrow mesenchymal stem cell retention and survival.
3.Predictive modeling of transient arrhythmia after PCI in patients with acute coronary syndromes
Zhiqiang LIU ; Zhikun ZHAO ; Wei MI ; Gang WANG ; Liang LI
The Journal of Practical Medicine 2025;41(13):2025-2032
Objective To explore the factors affecting the occurrence of transient arrhythmia after percuta-neous coronary intervention(PCI)in patients with acute coronary syndromes(ACS),to establish a risk prediction model,and to test the prediction effect.Methods 480 ACS patients who underwent PCI in Western Theater Air Force Hospital of PLA from August 2022 to February 2024 were selected as study subjects and were divided into 336 cases in the construct group and 144 cases in the validation group according to the ratio of 7:3.The data of the construct group were used to construct the model,and the validation group was used to validate the model.The patients in the constructed group were divided into 84 cases in the occurrence group and 252 cases in the non-occurrence group according to whether they had experienced postoperative transient arrhythmia,and the validation group was divided into 36 cases in the occurrence group and 108 cases in the non-occurrence group.The baseline data of the study subjects in the two groups were observed,and the predictive value of continuous variables was analyzed using the ROC experiment;the influencing factors of the occurrence of transient arrhythmia after PCI in ACS patients were analyzed using multifactorial logistic regression;the Nomogram prediction model was constructed using the R language;and the model was evaluated and validated using calibration curves and decision curves.Results The results of a one-way analysis of the constructed group showed that older age,the presence of a history of diabetes mellitus,the time from onset to admission≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS(P<0.05),and the prediction model established accordingly had an AUC of 0.865 and a 95%CI of 0.804~0.927,which was effective in predicting the occurrence of transient arrhythmia after PCI in patients with ACS.The model performed well in predicting the occurrence of transient arrhythmia after PCI,with a C-index of 0.858(0.753~0.865),and provided a good stan-dardized net benefit when its risk threshold was between 0.10 to 0.96.The validation group ROC curve and calibra-tion curve results are good,with an AUC of 0.846 and a C-index of 0.840(0.737~0.851),suggesting that the model has a good external predictive efficacy.The results of the validation group decision curve analysis indicated that the model could provide better standardized net returns when the risk threshold was between 0.06 and 0.94.Conclusion The results of univariate analysis showed that older age,the presence of a history of diabetes melli-tus,onset-to-admission time≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS,and the Nomogram model constructed on the basis of these four influenc-ing factors could effectively predict the risk of transient arrhythmia after PCI in patients with ACS.
5.Clinical Diagnosis and Prognosis Evaluation of Serum LRG1 and DPP4 Levels in Patients with Acute Watershed Cerebral Infarction
Leihua JIA ; Zhikun LÜ ; Mengmeng WEI ; Guozhen LI
Journal of Modern Laboratory Medicine 2025;40(2):98-103
Objective To investigate the diagnostic and prognostic value of serum leucine-rich alpha-2-glycoprotein 1(LRG1)and dipeptidyl peptidase 4(DPP4)levels in patients with acute cerebral watershed infarction(ACWI).Methods Selected 150 ACWI patients treated in the Baoding Second Central Hospital from January 2022 to December 2023 as the study subjects(ACWI group),and another 120 volunteers who underwent physical examinations were regarded as the control group.According to the prognosis of ACWI patients,they were separated into a good prognosis group(n=98)and a poor prognosis group(n=52).ELISA was used to detect serum LRG1,DPP4 and carcinoembryonic amtigen(CEA)levels,a biochemical analyzer was used to detect levels of albumin(ALB),adenosine deaminase(ADA),creatinine(Cre).Multivariate logistic regression was applied to analyze the influencing factors of poor prognosis in ACWI patients.Spearman correlation analysis of LRG1 and DPP4 levels with NIHSS and mRS scores in the ACWI group.The ROC curve was applied to analyze the diagnostic value of LRG1 and DPP4 levels for the occurrence of ACWI and prognosis,and Z-test was used to compare the differences in AUC.Results The serum LRG1(56.03±16.11pg/ml)and DPP4(9.90±3.25ng/L)levels in ACWI patients were higher than those in the control group(41.78±12.54pg/ml,7.34±2.32ng/L),the differences were statistically significant(t=7.951,7.272,all P<0.001).ACWI patients with poor prognosis had higher National Institute of Health Stroke Scale NIHSS scores,mRS scores,larger infarct proportion,LRG1 and DPP4 levels than those with good prognosis(t/χ2=3.258~17.208),but had lower ALB levels than those with good prognosis(t=3.143),the differences were statistically significant(all P<0.001).Multivariate logistic regression analysis showed that large area infarction,increased NIHSS score,mRS score,LRG1 and DPP4 levels were independent risk factors for poor prognosis in ACWI patients(Wald χ2=4.358~6.000,all P<0.05),while elevated ALB was an independent protective factor for poor prognosis in ACWI patients(Wald χ2=4.535,P<0.05).Spearman correlation analysis showed a positive correlation between serum LRG1 and DPP4 levels in ACWI patients(r=0.446,P<0.001).ROC curve analysis showed that the AUC(95%CI)for diagnosing ACWI with serum LRG1 and DPP4 were 0.788(0.734~0.835)and 0.790(0.736~0.837),respectively,while the AUC(95%CI)for combined diagnosis was 0.922(0.883~0.951),which was better than individual diagnosis(Z=5.798,5.612,all P<0.05).The AUC(95%CI)of LRG1 and DPP4 in diagnosing ACWI patients with poor prognosis was 0.796(0.722~0.857)and 0.800(0.727~0.861),respectively,and the AUC(95%CI)of combined diagnosis was 0.924(0.869~0.961),which was better than their respective individual diagnoses(Z=2.891,4.222,all P<0.05).Conclusion LRG1 and DPP4 levels are higher in the serum of ACWI patients and higher in patients with poor prognosis.The two levels are positively correlated,and the combination has a certain value in diagnosing the occurrence of ACWI and poor prognosis,which provides a theoretical basis for clinical diagnosis.
6.Clinical Diagnosis and Prognosis Evaluation of Serum LRG1 and DPP4 Levels in Patients with Acute Watershed Cerebral Infarction
Leihua JIA ; Zhikun LÜ ; Mengmeng WEI ; Guozhen LI
Journal of Modern Laboratory Medicine 2025;40(2):98-103
Objective To investigate the diagnostic and prognostic value of serum leucine-rich alpha-2-glycoprotein 1(LRG1)and dipeptidyl peptidase 4(DPP4)levels in patients with acute cerebral watershed infarction(ACWI).Methods Selected 150 ACWI patients treated in the Baoding Second Central Hospital from January 2022 to December 2023 as the study subjects(ACWI group),and another 120 volunteers who underwent physical examinations were regarded as the control group.According to the prognosis of ACWI patients,they were separated into a good prognosis group(n=98)and a poor prognosis group(n=52).ELISA was used to detect serum LRG1,DPP4 and carcinoembryonic amtigen(CEA)levels,a biochemical analyzer was used to detect levels of albumin(ALB),adenosine deaminase(ADA),creatinine(Cre).Multivariate logistic regression was applied to analyze the influencing factors of poor prognosis in ACWI patients.Spearman correlation analysis of LRG1 and DPP4 levels with NIHSS and mRS scores in the ACWI group.The ROC curve was applied to analyze the diagnostic value of LRG1 and DPP4 levels for the occurrence of ACWI and prognosis,and Z-test was used to compare the differences in AUC.Results The serum LRG1(56.03±16.11pg/ml)and DPP4(9.90±3.25ng/L)levels in ACWI patients were higher than those in the control group(41.78±12.54pg/ml,7.34±2.32ng/L),the differences were statistically significant(t=7.951,7.272,all P<0.001).ACWI patients with poor prognosis had higher National Institute of Health Stroke Scale NIHSS scores,mRS scores,larger infarct proportion,LRG1 and DPP4 levels than those with good prognosis(t/χ2=3.258~17.208),but had lower ALB levels than those with good prognosis(t=3.143),the differences were statistically significant(all P<0.001).Multivariate logistic regression analysis showed that large area infarction,increased NIHSS score,mRS score,LRG1 and DPP4 levels were independent risk factors for poor prognosis in ACWI patients(Wald χ2=4.358~6.000,all P<0.05),while elevated ALB was an independent protective factor for poor prognosis in ACWI patients(Wald χ2=4.535,P<0.05).Spearman correlation analysis showed a positive correlation between serum LRG1 and DPP4 levels in ACWI patients(r=0.446,P<0.001).ROC curve analysis showed that the AUC(95%CI)for diagnosing ACWI with serum LRG1 and DPP4 were 0.788(0.734~0.835)and 0.790(0.736~0.837),respectively,while the AUC(95%CI)for combined diagnosis was 0.922(0.883~0.951),which was better than individual diagnosis(Z=5.798,5.612,all P<0.05).The AUC(95%CI)of LRG1 and DPP4 in diagnosing ACWI patients with poor prognosis was 0.796(0.722~0.857)and 0.800(0.727~0.861),respectively,and the AUC(95%CI)of combined diagnosis was 0.924(0.869~0.961),which was better than their respective individual diagnoses(Z=2.891,4.222,all P<0.05).Conclusion LRG1 and DPP4 levels are higher in the serum of ACWI patients and higher in patients with poor prognosis.The two levels are positively correlated,and the combination has a certain value in diagnosing the occurrence of ACWI and poor prognosis,which provides a theoretical basis for clinical diagnosis.
7.Predictive modeling of transient arrhythmia after PCI in patients with acute coronary syndromes
Zhiqiang LIU ; Zhikun ZHAO ; Wei MI ; Gang WANG ; Liang LI
The Journal of Practical Medicine 2025;41(13):2025-2032
Objective To explore the factors affecting the occurrence of transient arrhythmia after percuta-neous coronary intervention(PCI)in patients with acute coronary syndromes(ACS),to establish a risk prediction model,and to test the prediction effect.Methods 480 ACS patients who underwent PCI in Western Theater Air Force Hospital of PLA from August 2022 to February 2024 were selected as study subjects and were divided into 336 cases in the construct group and 144 cases in the validation group according to the ratio of 7:3.The data of the construct group were used to construct the model,and the validation group was used to validate the model.The patients in the constructed group were divided into 84 cases in the occurrence group and 252 cases in the non-occurrence group according to whether they had experienced postoperative transient arrhythmia,and the validation group was divided into 36 cases in the occurrence group and 108 cases in the non-occurrence group.The baseline data of the study subjects in the two groups were observed,and the predictive value of continuous variables was analyzed using the ROC experiment;the influencing factors of the occurrence of transient arrhythmia after PCI in ACS patients were analyzed using multifactorial logistic regression;the Nomogram prediction model was constructed using the R language;and the model was evaluated and validated using calibration curves and decision curves.Results The results of a one-way analysis of the constructed group showed that older age,the presence of a history of diabetes mellitus,the time from onset to admission≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS(P<0.05),and the prediction model established accordingly had an AUC of 0.865 and a 95%CI of 0.804~0.927,which was effective in predicting the occurrence of transient arrhythmia after PCI in patients with ACS.The model performed well in predicting the occurrence of transient arrhythmia after PCI,with a C-index of 0.858(0.753~0.865),and provided a good stan-dardized net benefit when its risk threshold was between 0.10 to 0.96.The validation group ROC curve and calibra-tion curve results are good,with an AUC of 0.846 and a C-index of 0.840(0.737~0.851),suggesting that the model has a good external predictive efficacy.The results of the validation group decision curve analysis indicated that the model could provide better standardized net returns when the risk threshold was between 0.06 and 0.94.Conclusion The results of univariate analysis showed that older age,the presence of a history of diabetes melli-tus,onset-to-admission time≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS,and the Nomogram model constructed on the basis of these four influenc-ing factors could effectively predict the risk of transient arrhythmia after PCI in patients with ACS.
8.Effect of locking plate combined with cortical screw internal fixation on ankle function and quality of life in patients with ankle fracture combined with inferior tibiofibular separation
Zhikun WEI ; Xudong WANG ; Jinjie YANG ; Pengyan NIU ; Fei SHAO ; Shaohai REN
Journal of Clinical Surgery 2024;32(1):71-74
Objective To investigate the effect of locking plate combined with cortical screw internal fixation on ankle function and quality of life in patients with ankle fracture with tibiofibular separation.Methods A total of 120 patients with ankle fracture and distal tibiofibular separation treated in our hospital from May 2020 to December 2021 were selected and divided into control group and observation group according to random number table method,with 60 patients/group.The control group was treated with cortical screw fixation alone,and the observation group was treated with locking plate combined with cortical screw internal fixation.Before surgery and 6 months after surgery,the recovery function of the two groups was compared.X-ray,operation duration,healing time,intraoperative blood loss,postoperative complications were compared,and the living ability of the two groups of patients was evaluated.Results Before treatment,there was no difference in joint function between the two groups(P>0.05).After treatment,the longest walking of the control group(15.89±0.85),foot alignment(15.06±0.71),pain response(29.03±4.48)and ground walking(15.65±0.59).The longest walking distance(16.19±0.87),foot alignment(15.29±0.76),pain response(31.24±4.55)and ground walking(15.96±0.68)in the observation group,which were higher than those in control group(P<0.05).Compared with the control group,the intraoperative blood loss and healing time in the observation group were lower(P<0.05).BI index of the two groups before treatment had no difference(P>0.05);After treatment,BI index of observation group was higher than that of control group(P<0.05).There was no difference in the total complication rate between the two groups(P>0.05).Conclusion Locking plate combined with cortical screw internal fixation has a good therapeutic effect on improving ankle function,reducing intraoperative blood loss,promoting healing and improving behavioral ability in the treatment of ankle fracture combined with hypotibiofibular syndesmosis injury.
9.Exploration and clinical validation of the repair mode of the sclerotic zone of steroid-induced osteonecrosis of the femoral head based on Tandem Mass Tags technology
Zhikun ZHUANG ; Mincong HE ; Tianye LIN ; Rongkai WU ; Jinhua GUO ; Zhaoke WU ; Qiushi WEI
Chinese Journal of Tissue Engineering Research 2024;28(14):2191-2196
BACKGROUND:The sclerotic zone in the femoral head is an important imaging feature in the progression of steroid-induced femoral head necrosis,which is associated with disease prognosis.Peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α)has been shown to possess biological activities such as osteogenesis,angiogenesis and anti-mitochondrial apoptosis,which may be closely related to bone repair of steroid-induced femoral head necrosis. OBJECTIVE:To screen for the differential proteins in the sclerotic zone of steroid-induced osteonecrosis of the femoral head versus the normal zone,to screen for hub proteins in the sclerotic zone,and to verify the differential expression of hub proteins in the femoral head specimens following steroid-induced femoral head necrosis,and to to explore the repair pattern of the sclerotic zone following steroid-induced femoral head necrosis. METHODS:Femoral head samples were collected from patients with steroid-induced osteonecrosis of the femoral head receiving total hip arthroplasty.The differentially expressed genes in the sclerotic zone and the normal zone were screened by Tandem Mass Tags and analyzed by GO and KEGG signaling pathways to construct a protein-protein interaction network and screen hub genes.In addition,the expression of hub genes in the sclerotic zone was verified by immunohistochemistry and western blot. RESULTS AND CONCLUSION:Quantitative protein profiling by Tandem Mass Tags revealed that 609 proteins were significantly differentially expressed(Log2FC>1.20,Log2FC<0.84 and P<0.05)in the sclerotic zone of the femoral head compared with the normal zone,of which 290 proteins were upregulated and 319 proteins were downregulated.The GO and KEGG pathway enrichment analyses revealed that among the top 10 enriched pathways,Wnt signaling pathway and life-cycle regulatory pathway were closely related to bone repair;in the life-cycle regulatory pathway,PGC-1α was one of the important proteins.In addition,western blot results verified the low expression of PGC-1α and NRF1 in the sclerotic zone and high expression of Cleaved Caspase-3 in the sclerotic zone compared with the normal zone of steroid-induced femoral head necrosis specimens.Light microscopic immunohistochemical results showed the distribution of PGC-1α,NRF1 and Cleaved Caspase-3 positive expression in the sclerotic and normal zones in the femoral head tissue specimens,indicating the presence of their expression in bone trabeculae,osteoblasts and bone marrow.In contrast,the brown area of the sclerotic zone of femoral head necrosis stained darker and showed more obvious expression of Cleaved Caspase-3.To conclude,in the sclerotic zone of steroid-induced femoral head necrosis,biological behaviors including activation of osteogenesis-related pathways such as Wnt and oxidative apoptosis characterized by low expression of PGC-1 are observed.Low expression of PGC-1α in the sclerotic zone of steroid-induced femoral head necrosis may be associated with the activation of oxidative apoptosis.
10.Establishment of MRI classification for traumatic osteonecrosis of the femoral head and its correlation with femoral head collapse
Zhikun ZHUANG ; Ziqi LI ; Shihua GAO ; Hanglin QIU ; Zhiqing XU ; Zhibing GONG ; Qingwen ZHANG ; Zhaoke WU ; Wei HE
Chinese Journal of Orthopaedics 2024;44(13):881-888
Objective:To establish a classification system for the repair band in the subchondral bone origination point in MRI for traumatic osteonecrosis of the femoral head (ONFH) and preliminarily explore the correlation between this classification and the progression of femoral head collapse.Methods:A retrospective analysis was conducted on 73 cases of traumatic ON-FH treated at the Quanzhou Orthopedic-traumatological hospital from January 2000 to December 2019. Among them, there were 46 males and 27 females with an average age of 34.9±8.3 years (range 19-55 years). Clinical and radiological data such as age, gender, side, fracture classification, reduction quality, JIC classification, and bone repair band (BRB) classification were recorded. The progression of traumatic ONFH was assessed using the ARCO staging system, with stages IIIA and IIIB defined as mild collapse and progressive collapse, respectively. The BRB classification was established based on MRI findings, and the inter- and intra-observer consistency of the BRB classification was analyzed using Kappa test. The correlation between the BRB classification and progressive femoral head collapse was analyzed using the Kaplan-Meier survival curve and binary variable Cox regression analysis.Results:According to the BRB classification, 73 cases were divided into type 1 with superficial lesion in 38.4%, type 2 with uncertain lesion in 21.9%, and type 3 with extensive lesion in 39.7%. The inter-observer consistency Kappa value for the BRB classification was 0.798, and the intra-observer consistency Kappa value was 0.896, indicating a high level of consistency. A follow-up of 73 cases (54.8±34.9 months, range 24-165 months) showed a significant correlation between the BRB classification and ARCO staging at the last follow-up (χ 2=37.556, P<0.001), with progression to stages IIIA and IIIB as follows: type 1 had 3 and 1 cases, type 2 had 4 and 1 cases, and type 3 had 14 and 12 cases, respectively. Using the occurrence of progressive collapse (stage IIIB) as the endpoint, the risk of progression to stage IIIB for type 2 was not statistically different from type 1 [ HR=1.766, 95% CI (0.465, 6.702), P=0.403]; the risk of progression to stage IIIB for type 3 was significantly higher than for type 1 [ HR=15.126, 95% CI (4.708, 48.592), P<0.001]. Conclusion:The BRB classification is closely related to the progression of traumatic ONFH and is an independent risk factor for predicting the occurrence of progressive collapse; this classification is helpful for early diagnosis and predicting the progression of collapse and treatment plan decision-making.

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