1.Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy.
Yong WANG ; Kewen HE ; Yang ZHANG ; Yunhao CHEN ; Shijie WANG ; Kunlong ZHAO ; Zhiguo LIU ; Man HU
Journal of Pharmaceutical Analysis 2025;15(3):101082-101082
Real-time, noninvasive programmed death-ligand 1 (PD-L1) testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy. However, the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography (PET/CT) remains limited. This investigation involved the synthesis of [18F]AlF-NOTA-PCP2, which is a novel peptide-based radiolabeled tracer that targets PD-L1, and evaluated its imaging capabilities in orthotopic glioblastoma (GBM) models. Using this tracer, we could noninvasively monitor radiation-induced PD-L1 changes in GBM. [18F]AlF-NOTA-PCP2 exhibited high radiochemical purity (>95%) and stability up to 4 h after synthesis. It demonstrated specific, high-affinity binding to PD-L1 in vitro and in vivo, with a dissociation constant of 0.24 nM. PET/CT imaging, integrated with contrast-enhanced magnetic resonance imaging, revealed significant accumulation of [18F]AlF-NOTA-PCP2 in orthotopic tumors, correlating with blood-brain barrier disruption. After radiotherapy (15 Gy), [18F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51% ± 0.73% to 12.04% ± 1.43%, indicating enhanced PD-L1 expression consistent with immunohistochemistry findings. Fractionated radiation (5 Gy × 3) further amplified PD-L1 upregulation (13.9% ± 1.54% ID/cc) compared with a single dose (11.48% ± 1.05% ID/cc). Taken together, [18F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.
2.Relationship between lactate level and clearance during extracorporeal life support and prognosis in elderly cardiac intensive care patients
Kewen CHEN ; Xinhua MA ; Kang HUANG ; Huan HUANG ; Songbai WU ; Yao DAI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(11):1479-1483
Objective To investigate the presumed correlation between lactate level and clearance during extracorporeal life support(ECLS)and death in elderly cardiac intensive care patients.Methods A total of 93 elderly cardiac intensive care patients who received ECLS in Department of Critical Care Medicine,Xiangya Medical College Affiliated Changsha Hospital,Central South University,from March 2019 to October 2024 were retrospectively included to manage low cardiac production syndrome after major cardiac surgery.According to hospital outcomes,the patients were divided into a death group(n=45)and a survival group(n=48).Blood lactate measurements were performed every 4 hours from the beginning of ECLS treatment to calculate peak lactate and lactate clearance rate(LCR).Routine ICU scores,such as sequential organ failure score(SOFA)and reactive organ dysfunction(ROD)score,and postoperative complications were recorded.Results The death group received larger amounts of packed red blood cell concentrate,fresh frozen plasma and platelet concentrate,and exhibited higher ratios of norepinephrine and epinephrine administration and higher incidences of re-thoracotomy and hemolytic episodes when compared with the survival group(P<0.05,P<0.01).At the end of ECLS,higher SOFA and ROD scores were observed in the death group(P<0.01).The death group also demonstrated higher lactate level from venoarterial ECLS(P<0.001)and increased median peak lactate level,but lower median LCR than the survival group(P<0.01).Multivariate logistic analysis showed that peak lactate and LCR were independent prognostic factors in the elderly cardiac ICU patients(P<0.05,P<0.01).The AUC value(95%CI)of peak lactate and LCR in predicting patient outcomes was 0.723(95%CI:0.615-0.831)and 0.846(95%CI:0.761-0.932),respectively,and the value of their combination in predicting in-hospital death was 0.846(95%CI:0.762-0.931),with a sensitivity of 0.629 and a specificity of 0.937.Conclusion Lactate level and its clearance rate during ECLS can affect the survival rate of elderly cardiac intensive care patients.Peak lactate and LCR can predict the prognosis of elderly cardiac intensive care patients,and can be used as prognostic indicators for clinical monitoring.
3.Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy
Yong WANG ; Kewen HE ; Yang ZHANG ; Yunhao CHEN ; Shijie WANG ; Kunlong ZHAO ; Zhiguo LIU ; Man HU
Journal of Pharmaceutical Analysis 2025;15(3):599-609
Real-time,noninvasive programmed death-ligand 1(PD-L1)testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy.However,the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography(PET/CT)remains limited.This investigation involved the synthesis of[18F]AlF-NOTA-PCP2,which is a novel peptide-based radiolabeled tracer that targets PD-L1,and evaluated its imaging capabilities in orthotopic glioblastoma(GBM)models.Using this tracer,we could noninvasively monitor radiation-induced PD-L1 changes in GBM.[18F]AlF-NOTA-PCP2 exhibited high radiochemical purity(>95%)and stability up to 4 h after synthesis.It demonstrated specific,high-affinity binding to PD-L1 in vitro and in vivo,with a dissociation constant of 0.24 nM.PET/CT imaging,integrated with contrast-enhanced magnetic resonance imaging,revealed significant accumulation of[18F]AlF-NOTA-PCP2 in orthotopic tumors,correlating with blood-brain barrier disruption.After radiotherapy(15 Gy),[18F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51%±0.73%to 12.04%±1.43%,indicating enhanced PD-L1 expression consistent with immunohisto-chemistry findings.Fractionated radiation(5 Gy × 3)further amplified PD-L1 upregulation(13.9%±1.54%ID/cc)compared with a single dose(11.48%±1.05%ID/cc).Taken together,[18F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.
4.Physical therapy for Parkinson's disease from 2014 to 2023:a bibliometric analysis
Dandan LU ; Jingzhi YAO ; Zi LI ; Kewen WANG ; Xinliao SUN ; Jianmin CHEN ; Jianwen XU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(8):906-913
Objective To analyze the research hotspots and frontier trends in the field of physical therapy for Parkinson's disease(PD)from 2014 to 2023.Methods Relevant literatures published from January,2014 to December,2023 were retrieved from the Web of Science Core Collection.CiteSpace 6.3.R1 was used to conduct bibliometric analysis,generating visual maps of coun-tries,institutions,keyword co-occurrence,burst terms,timelines and clustering,and they were summarized based on both visual results and literature content.Results A total of 400 articles were included.The United States had the highest publication volume,followed by China,Italy and Brazil,and the international collaboration was relatively active.Major contributing institutions included Northwestern University,Rush University,Karolinska Institutet and Universidade de S?o Paulo.Keyword co-oc-currence analysis showed that researches mainly focused on interventions such as exercise,postural control,aero-bic exercise and transcranial direct current stimulation.Burst detection analysis showed that keywords with high attention in recent years included motor symptoms,executive function,resistance training and noninvasive brain stimulation.The timeline map indicated a shift in research themes from early focus on electrical stimulation to in-tegrated interventions involving both motor and cognitive functions.Conclusion Over the past decade,researches on physical therapy for PD has shown steady growth,with increasing diver-sity in intervention strategies.There is a clear trend toward multidimensional integration and interdisciplinary col-laboration.Future studies should strengthen interventions targeting non-motor symptoms and promote the clinical application of new rehabilitation technologies.
5.Physical therapy for Parkinson's disease from 2014 to 2023:a bibliometric analysis
Dandan LU ; Jingzhi YAO ; Zi LI ; Kewen WANG ; Xinliao SUN ; Jianmin CHEN ; Jianwen XU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(8):906-913
Objective To analyze the research hotspots and frontier trends in the field of physical therapy for Parkinson's disease(PD)from 2014 to 2023.Methods Relevant literatures published from January,2014 to December,2023 were retrieved from the Web of Science Core Collection.CiteSpace 6.3.R1 was used to conduct bibliometric analysis,generating visual maps of coun-tries,institutions,keyword co-occurrence,burst terms,timelines and clustering,and they were summarized based on both visual results and literature content.Results A total of 400 articles were included.The United States had the highest publication volume,followed by China,Italy and Brazil,and the international collaboration was relatively active.Major contributing institutions included Northwestern University,Rush University,Karolinska Institutet and Universidade de S?o Paulo.Keyword co-oc-currence analysis showed that researches mainly focused on interventions such as exercise,postural control,aero-bic exercise and transcranial direct current stimulation.Burst detection analysis showed that keywords with high attention in recent years included motor symptoms,executive function,resistance training and noninvasive brain stimulation.The timeline map indicated a shift in research themes from early focus on electrical stimulation to in-tegrated interventions involving both motor and cognitive functions.Conclusion Over the past decade,researches on physical therapy for PD has shown steady growth,with increasing diver-sity in intervention strategies.There is a clear trend toward multidimensional integration and interdisciplinary col-laboration.Future studies should strengthen interventions targeting non-motor symptoms and promote the clinical application of new rehabilitation technologies.
6.Relationship between lactate level and clearance during extracorporeal life support and prognosis in elderly cardiac intensive care patients
Kewen CHEN ; Xinhua MA ; Kang HUANG ; Huan HUANG ; Songbai WU ; Yao DAI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(11):1479-1483
Objective To investigate the presumed correlation between lactate level and clearance during extracorporeal life support(ECLS)and death in elderly cardiac intensive care patients.Methods A total of 93 elderly cardiac intensive care patients who received ECLS in Department of Critical Care Medicine,Xiangya Medical College Affiliated Changsha Hospital,Central South University,from March 2019 to October 2024 were retrospectively included to manage low cardiac production syndrome after major cardiac surgery.According to hospital outcomes,the patients were divided into a death group(n=45)and a survival group(n=48).Blood lactate measurements were performed every 4 hours from the beginning of ECLS treatment to calculate peak lactate and lactate clearance rate(LCR).Routine ICU scores,such as sequential organ failure score(SOFA)and reactive organ dysfunction(ROD)score,and postoperative complications were recorded.Results The death group received larger amounts of packed red blood cell concentrate,fresh frozen plasma and platelet concentrate,and exhibited higher ratios of norepinephrine and epinephrine administration and higher incidences of re-thoracotomy and hemolytic episodes when compared with the survival group(P<0.05,P<0.01).At the end of ECLS,higher SOFA and ROD scores were observed in the death group(P<0.01).The death group also demonstrated higher lactate level from venoarterial ECLS(P<0.001)and increased median peak lactate level,but lower median LCR than the survival group(P<0.01).Multivariate logistic analysis showed that peak lactate and LCR were independent prognostic factors in the elderly cardiac ICU patients(P<0.05,P<0.01).The AUC value(95%CI)of peak lactate and LCR in predicting patient outcomes was 0.723(95%CI:0.615-0.831)and 0.846(95%CI:0.761-0.932),respectively,and the value of their combination in predicting in-hospital death was 0.846(95%CI:0.762-0.931),with a sensitivity of 0.629 and a specificity of 0.937.Conclusion Lactate level and its clearance rate during ECLS can affect the survival rate of elderly cardiac intensive care patients.Peak lactate and LCR can predict the prognosis of elderly cardiac intensive care patients,and can be used as prognostic indicators for clinical monitoring.
7.Metabolomics analysis of serum and urine in patients with traumatic spinal cord injury
Jiating SONG ; Jianmin CHEN ; Kewen WANG ; Lanying HUANG ; Senming XU ; Yuchang GUI ; Jianwen XU
Chinese Journal of Tissue Engineering Research 2024;28(32):5085-5090
BACKGROUND:Traumatic spinal cord injury primarily relies on scale assessment and imaging examinations in clinical practice.However,there are limitations in predicting the prognosis of the injury.Therefore,the use of metabolomics technology for biomarker screening is significant for estimating the extent of damage,injury and recovery,as well as developing new therapies. OBJECTIVE:To characterize the metabolic features of patients with traumatic spinal cord injury using metabolomics technology and explore potential biomarkers and disrupted metabolic pathways. METHODS:Serum and urine samples were collected from 20 patients with traumatic spinal cord injury(observation group)and 10 healthy subjects(control group).Metabolites were analyzed and multivariate statistical analysis was then performed for data processing to screen differential metabolites.Metabolic pathway enrichment was performed using MetaboAnalyst software.Logistic regression was applied to construct a biomarker combination model,and its relationship with the American Spinal Injury Association grading was analyzed. RESULTS AND CONCLUSION:Significant differences in 160 and 73 metabolites were detected in the serum and urine samples of the two groups,respectively.Pathway enrichment analysis showed evident disturbances in lipid metabolism after traumatic spinal cord injury,including sphingolipid,arachidonic acid,α-linolenic acid,and arachidonic acid metabolism,as well as glycerophospholipid and inositol phosphate biosynthesis.The combination of two identified biomarkers,telmisartan and quercetin glycoside,showed a correlation with the American Spinal Injury Association grading in both serum and urine levels.Thus,metabolomics technology provides assistance in further understanding the pathological mechanisms of traumatic spinal cord injury and screening therapeutic targets.The identified metabolic biomarker combination may serve as a reference for assessing the severity of traumatic spinal cord injury.
8.The efficacy of pancreatic fluid molecular biomarkers for diagnosis of pancreatic cancer
Yu LIU ; Li WANG ; Bingfang CHEN ; Kewen SUN ; Yin ZHANG
The Journal of Practical Medicine 2024;40(21):3101-3106
Pancreatic cancer(PC)is one of the deadliest malignant tumors worldwide,known as the'king of cancers'due to its insidious onset,high malignancy,and high mortality rate.PC is highly malignant and pro-gresses rapidly,but its onset is insidious with atypical early symptoms,making it difficult to detect early lesions through conventional imaging studies.It is usually only discovered when symptoms like jaundice,abdominal and back pain occur.Surgical resection is currently the only curative option for PC.However,due to the difficulty in early diagnosis,the majority of patients are already in the middle to late stages at the time of diagnosis,missing the opportunity for surgery.Studies have confirmed that the progression of pancreatic cancer is relatively slow,with the initial tumor cells requiring at least 15 years to gain metastatic ability.Therefore,timely detection of pancreatic cancer through tumor markers could significantly improve the survival rate of patients.The most widely used and diagnostically valuable tumor marker in clinical practice is Carbohydrate antigen 199(CA199).However,due to about 3%~7%of pancreatic cancer patients being Lewis antigen-negative blood types and not expressing CA19-9,its sensitivity is only 79%~81%,which does not provide good efficacy for the diagnosis of pancreatic cancer.Pan-creatic juice,as a fluid near the tumor,has attracted much attention as a good source of tumor-related biomarkers.Many studies have confirmed the accuracy of using proteins,DNA,and exosomes in pancreatic juice for the diag-nosis of pancreatic cancer,showing great prospects for pancreatic juice as a source of tumor markers for the diagnosis of pancreatic cancer.Therefore,this thesis reviews the efficacy of pancreatic juice as a specimen for the diagnosis of pancreatic cancer.
9.Research advances on treatment of recurrent IgA nephropathy after kidney transplantation
Kewen CHEN ; Jinghai LIU ; Pei ZHANG ; Junhao YU ; Mingxing SUI ; Li ZENG
Chinese Journal of Organ Transplantation 2024;45(9):636-640
IgA nephropathy (IgAN) is one common type of glomerulonephritis caused by a deposition of immune complexes in mesangium and partial capillary loops. It is also an important risk factor for end-stage renal disease (ESRD). Kidney transplantation (KT) has been an ultimate treatment for IgAN patients progressing into ESRD. However, there is still a high risk of recurrence after transplantation. Currently no effective treatment is available for recurrent IgAN. This review summarized the latest researches of managing IgAN recurrence after KT, such as optimal treatment, immunosuppression, complement therapy and surgery.
10.Bioinformatics Analysis and Experimental Validation of Two Blood Stasis Patterns in Ischemic Stroke
Chenxi LIANG ; Xiaolu LI ; Jianmin CHEN ; Kewen WANG ; Yuchang GUI ; Yuqin ZHANG ; Jianwen XU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(10):2695-2702
Objective To explore the differential expression genes(DEGs)and related signaling pathways of the Qi deficiency and blood stasis(QDBS)and Yin deficiency and blood stasis(YDBS)syndromes in ischemic stroke(IS)at the molecular level,elucidating the potential mechanisms and biological basis of blood stasis syndrome in IS.Methods The mRNA expression profile dataset GSE100235 of the two syndromes of IS rats was downloaded from the GEO database,and the limma package of R language was used to screen DEGs.Subsequently,GO and KEGG analyses were performed using the DAVID database.The miRDB and miRWalk databases were used to predict the miRNAs of DEGs,and aa miRNA-mRNA regulatory network was constructed.A protein-protein interaction network was built using the STRING database,and the cytoHubba plug-in was utilized to identify the core target genes.The rat model of QDBS in IS was established by exhaustive swimming training combined with modified Longa's thread embolism,and the rat model of YDBS in IS was established by hydrocortisone injection and thread embolism.RT-qPCR was employed to validate the expression levels of core target genes in rat brain tissues of the two groups.Results A total of 47 DEGs were identified.These genes were mainly involved in biological processes such as neuronal apoptosis,inflammatory response,and adaptive immune response,as well as pathways related to lipid metabolism,atherosclerosis,and C-type lectin receptor signaling.The miRNA-mRNA interaction network consisted of 64 nodes and 55 edges.Five core target genes were obtained,including Ccl2,Selp,Timp1,Ccr1l1,and Fpr1.Conclusion There are significantly differentially expressed genes in QDBS and YDBS syndrome of IS rats.These genes are involved in a variety of biological processes and pathways,and are most closely related to lipid metabolism and atherosclerosis signaling pathways.

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