1.A preclinical and first-in-human study of superstable homogeneous radiolipiodol for revolutionizing interventional diagnosis and treatment of hepatocellular carcinoma.
Hu CHEN ; Yongfu XIONG ; Minglei TENG ; Yesen LI ; Deliang ZHANG ; Yongjun REN ; Zheng LI ; Hui LIU ; Xiaofei WEN ; Zhenjie LI ; Yang ZHANG ; Syed Faheem ASKARI RIZVI ; Rongqiang ZHUANG ; Jinxiong HUANG ; Suping LI ; Jingsong MAO ; Hongwei CHENG ; Gang LIU
Acta Pharmaceutica Sinica B 2025;15(10):5022-5035
Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as 131I,177Lu, or 18F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, 18F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).
2.Research progress on the etiology and epidemiology of monkeypox
LIU Shan ; ZHANG Jingsong ; ZHANG Wenli ; WANG He ; ZHU Wenye ; SHA Kun
Journal of Preventive Medicine 2025;37(8):789-793,798
Monkeypox is a zoonotic disease caused by the monkeypox virus, which was previously limited to epidemics in Africa. Since 2022, monkeypox has rapidly spread worldwide, affecting 130 countries and regions. The World Health Organization declared it a public health emergency of international concern, in 2022 and 2024, respectively. The monkeypox virus has exhibited accelerated mutation rates, with diverse circulating strains. Children and men who have sex with men have emerged as the primary high-risk group. Additionally, the increase in asymptomatic infections and atypical mild rashes has complicated differential diagnosis, posing entirely challenges to the diagnosis, treatment, and prevention and control of monkeypox. This article reviews the research progress on the etiological characteristics, epidemiological features, clinical manifestations, and prevention and treatment strategies of monkeypox by retrieving the literature on monkeypox from January 1958 to January 2025, so as to provide the basis for the prevention and treatment of monkeypox.
3.The relationship between size distribution of circulating extracellular vesicles and coagulation function after cardiac surgery
Hongyu CAO ; Haoxiang YUAN ; Chao CHEN ; Yupeng JIAN ; Yuquan LI ; Xiaojun LIU ; Zhensheng MA ; Yan LI ; Jingsong OU
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(3):183-190
Objective:To investigate the relationship between the changes in extracellular vesicles (EVs) size distribution before and after cardiopulmonary bypass (CPB) cardiac surgery and postoperative coagulation function.Methods:A total of 103 patients undergoing cardiac surgery with CPB were enrolled. Venous blood samples were collected at preoperation, postoperative 12 h and 3 days. Additionally, 50 age- and gender-matched healthy volunteers served as a control group. EVs were isolated using gradient centrifugation, and their size distribution was assessed by dynamic light scattering (DLS). The relationship between EV size characteristics, including peak diameter, peak height, and interquartile range( IQR), and postoperative coagulation function was analyzed. Results:Compared to patients with normal postoperative coagulation function, those with postoperative coagulation dysfunction had lower size at peak and IQR, and significantly higher peak intensity. Logistic regression analysis indicated that elevated peak intensity and lower size at peak and IQR were risk factors for coagulation dysfunction. The area under the curve ( AUC) for diagnosing coagulation dysfunction with 12 h postoperative EVs peak intensity was 0.76, with a positive predictive value of 85% at the optimal cutoff of 8.2; the AUC for IQR was 0.84, with a sensitivity of 83%, specificity of 82%, and negative predictive value of 86% at the optimal cutoff of 125.05 nm. Conclusion:The size distribution of circulating EVs show a correlation with coagulation function after cardiac surgery with CPB and may serve as a novel biomarker to predict postoperative coagulation dysfunction.
4.Application of CRISPR-based one-pot droplet assay for BK virus nucleic acid detection
Yu LIU ; Jingsong XU ; Min LI ; Hua WANG
Chinese Journal of Laboratory Medicine 2025;48(6):743-749
Objective:To establish a method for quantitative detection of BK virus (BKV) nucleic acid using microfluidic droplet one-pot Recombinase polymerase amplification-clustered regularly interspaced short palindromic repeats, RPA-CRISPR/Cas13a.Methods:A methodology establishment study. Plasma or urine samples were collected from 50 post renal transplant patients and 40 healthy individuals in Renji Hospital, Shanghai Jiao Tong University School of Medicine, from May 16 to August 31, 2024, and the viral genomic DNA was extracted. In the renal transplant group, there were 28 males and 22 females aged (46.1±11.6) years; in the healthy control group, there were 21 males and 19 females aged (45.6±11.3) years. Three crRNAs were designed for screening the optimal crRNA in CRISPR/Cas13a reaction taking PCR product as templet. Two pairs of RPA primers targeting BKV sequences were designed and selected an optimal primer set from four combinations for RPA-CRISPR/Cas13a reaction. Microfluidic droplet generation chip was designed and fabricated for rapid quantitative detection of BKV nucleic acids, which was combined with a droplet reader. BKV plasmid standards were utilized to assess the detection sensitivity of the one-pot assay. The CRISPR droplet one-pot assay and qPCR were utilized to detect the BKV load in the above samples, respectively. The methodological consistency was then analyzed, and Kappa coefficients of the results were calculated using the Kappa test, and the correlation between the two methods was evaluated using linear regression analysis. Results:The RPA-CRISPR/Cas13a reaction system was combined with a droplet chip to establish a CRISPR microfluidic droplet one-pot assay for BKV detection. The sensitivity of the CRISPR microfluidic droplet one-pot assay for detecting BKV was 10 copies/ml, which surpassed that of qPCR (100 copies/ml) without cross-reaction with JC virus. Methodological consistency analysis demonstrated that the Kappa coefficient of the two methods was 0.96, and the coefficient of determination R 2 was 0.95. Conclusion:In this study, a novel BKV detection technology based on the one-pot CRISPR droplet assay was successfully established.
5.Establishment and application of a one-pot lyophilized CRISPR system for detecting CMV in liver transplant recipients
Junheng ZHANG ; Jingsong XU ; Yu LIU ; Haiqian HUANG ; Min LI ; Hua WANG
Chinese Journal of Laboratory Medicine 2025;48(10):1317-1322
Objective:To establish a one-pot lyophilized detection system based on recombinase polymerase amplification (RPA) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas13a) technology for the rapid diagnosis of cytomegalovirus (CMV) infection in liver transplantation recipients.Methods:This study is a methodology study. CRISPR RNA (crRNA) and RPA primers were designed targeting the CMV gene sequence. Optimal RPA primer sets were screened to establish the RPA-CRISPR/Cas13a-based CMV detection system. The limit of detection (LOD) was evaluated using gradient-diluted CMV plasmid standards. Cross-reactivity was assessed using genomic DNA from common opportunistic viruses in organ transplant recipients. Lyophilized reagents were validated with CMV-negative and positive samples. P-values were computed using two-sample t-tests for pairwise comparisons and one-way ANOVA for multi-group analyses to assess fluorescence value differences. Subsequently, lyophilized reagents were employed to detect 22 plasma samples from liver transplantation recipients collected at Renji Hospital, Shanghai Jiao Tong University School of Medicine, from June 3, 2024, to May 31, 2025. The test results were then compared with those obtained using quantitative real-time polymerase chain reaction (qPCR). Consistency between the two methods was evaluated using the Kappa coefficient calculated by Kappa test.Result:The established RPA-CRISPR/Cas13a system achieved a detection sensitivity of 1 copy/reaction and exhibited no cross-reactivity with other common opportunistic viruses in organ transplantation. Lyophilized RPA-CRISPR/Cas13a reagents demonstrated performance equivalent to non-lyophilized reagents. Concordance between lyophilized reagent detection and qPCR results for 22 clinical samples was 100% (22/22).Conclusion:A lyophilized CMV detection method based on RPA-CRISPR/Cas13a technology was successfully developed and validated for convenient diagnosing CMV infection in liver transplant recipients.
6.Correlation between magnetic resonance imaging characteristics and pain severity in joint damage related to Chikungunya virus infection as well as the assessment value of T2-Mapping value for the severity and prognosis of damage
Jingsong SUN ; Xiaozeng HUANG ; Yudong QIAN ; Ziwei LIU ; Cuiai DENG ; Ruiping WEN ; Xiujuan LIAO ; Zaopeng HE
Chinese Journal of Infection Control 2025;24(11):1563-1571
Objective To explore the magnetic resonance(MR)imaging characteristics of joint damage caused by Chikungunya virus(CHIKV)and its correlation with pain severity,and analyze the value of T2-Mapping in asse-ssing the severity and prognosis of such damage.Methods A multicenter retrospective study design was adopted,and patients with CHIKV infection accompanied by joint pain were included in analysis.Multi-joint MR scans were performed to assess joint effusion,synovial thickening,bone marrow edema,and cartilage damage.T2-Mapping values were measured.Pain severity was assessed using the Visual Analog Scale(VAS),and imaging findings were independently assessed by two radiologists.Results A total of 131 patients were included in the study.The inci-dence of joint cavity and/or synovial sac effusion was the highest(77.1%,n=101),with knee and ankle joint effu-sion accounting for 81.2%(severe,mild-moderate were 17 and 65 cases,respectively),other joint effusion were mild.78 cases had synovial thickening(14 and 64 were severe and mild-moderate cases,respectively),27 cases had tenosynovitis,21 cases had bone marrow edema(primarily in the knee and ankle joints).19 cases had cartilage damage,114 cases presented muscle soft tissue edema(17 and 97 were severe and mild-moderate cases,respective-ly),28 cases had Kager's fat pad edema.Patients with elevated T2-Mapping values exhibited more pronounced chronic joint pain,with T2-Mapping values in the cartilage damage site increasing by 40%-60%compared with normal cartilage site(19 cases in total).The T2-Mapping value for severely damaged soft tissue was(52.3+6.7)ms,while for mildly to moderately damaged soft tissue was(42.3±5.2)ms,both significantly higher than normal refe-rence values(<35 ms,both P<0.05).Among 17 patients with severe soft tissue damage,12 experienced persistent pain for over one month,with statistically significant differences in T2 values compared with those with mild-mode-rate damage(P<0.05).This further suggested that the degree of elevation in T2-Mapping values was closely related to the duration of pain and the severity of damage.After one-month follow-up,103 patients had pain relief.Among the 28 patients with ongoing pain,17 developed into subacute bone joint pain.Bone marrow edema(81.0%),ele-vation of T2-Mapping value of cartilage(89.5%),and severe synovial thickening(71.4%)were high-risk MR manifestations of subacute bone joint pain.The incidences of subacute joint cavity/sac effusion and subacute tenosy-novitis were 3.0%and 7.4%,respectively.Conclusion MR can clearly display the inflammatory and structural changes in CHIKV joint damage,and T2-Mapping values may serve as a potential imaging measurement parameter for assessing severity and prognosis of damage.
7.Correlation between magnetic resonance imaging characteristics and pain severity in joint damage related to Chikungunya virus infection as well as the assessment value of T2-Mapping value for the severity and prognosis of damage
Jingsong SUN ; Xiaozeng HUANG ; Yudong QIAN ; Ziwei LIU ; Cuiai DENG ; Ruiping WEN ; Xiujuan LIAO ; Zaopeng HE
Chinese Journal of Infection Control 2025;24(11):1563-1571
Objective To explore the magnetic resonance(MR)imaging characteristics of joint damage caused by Chikungunya virus(CHIKV)and its correlation with pain severity,and analyze the value of T2-Mapping in asse-ssing the severity and prognosis of such damage.Methods A multicenter retrospective study design was adopted,and patients with CHIKV infection accompanied by joint pain were included in analysis.Multi-joint MR scans were performed to assess joint effusion,synovial thickening,bone marrow edema,and cartilage damage.T2-Mapping values were measured.Pain severity was assessed using the Visual Analog Scale(VAS),and imaging findings were independently assessed by two radiologists.Results A total of 131 patients were included in the study.The inci-dence of joint cavity and/or synovial sac effusion was the highest(77.1%,n=101),with knee and ankle joint effu-sion accounting for 81.2%(severe,mild-moderate were 17 and 65 cases,respectively),other joint effusion were mild.78 cases had synovial thickening(14 and 64 were severe and mild-moderate cases,respectively),27 cases had tenosynovitis,21 cases had bone marrow edema(primarily in the knee and ankle joints).19 cases had cartilage damage,114 cases presented muscle soft tissue edema(17 and 97 were severe and mild-moderate cases,respective-ly),28 cases had Kager's fat pad edema.Patients with elevated T2-Mapping values exhibited more pronounced chronic joint pain,with T2-Mapping values in the cartilage damage site increasing by 40%-60%compared with normal cartilage site(19 cases in total).The T2-Mapping value for severely damaged soft tissue was(52.3+6.7)ms,while for mildly to moderately damaged soft tissue was(42.3±5.2)ms,both significantly higher than normal refe-rence values(<35 ms,both P<0.05).Among 17 patients with severe soft tissue damage,12 experienced persistent pain for over one month,with statistically significant differences in T2 values compared with those with mild-mode-rate damage(P<0.05).This further suggested that the degree of elevation in T2-Mapping values was closely related to the duration of pain and the severity of damage.After one-month follow-up,103 patients had pain relief.Among the 28 patients with ongoing pain,17 developed into subacute bone joint pain.Bone marrow edema(81.0%),ele-vation of T2-Mapping value of cartilage(89.5%),and severe synovial thickening(71.4%)were high-risk MR manifestations of subacute bone joint pain.The incidences of subacute joint cavity/sac effusion and subacute tenosy-novitis were 3.0%and 7.4%,respectively.Conclusion MR can clearly display the inflammatory and structural changes in CHIKV joint damage,and T2-Mapping values may serve as a potential imaging measurement parameter for assessing severity and prognosis of damage.
8.The relationship between size distribution of circulating extracellular vesicles and coagulation function after cardiac surgery
Hongyu CAO ; Haoxiang YUAN ; Chao CHEN ; Yupeng JIAN ; Yuquan LI ; Xiaojun LIU ; Zhensheng MA ; Yan LI ; Jingsong OU
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(3):183-190
Objective:To investigate the relationship between the changes in extracellular vesicles (EVs) size distribution before and after cardiopulmonary bypass (CPB) cardiac surgery and postoperative coagulation function.Methods:A total of 103 patients undergoing cardiac surgery with CPB were enrolled. Venous blood samples were collected at preoperation, postoperative 12 h and 3 days. Additionally, 50 age- and gender-matched healthy volunteers served as a control group. EVs were isolated using gradient centrifugation, and their size distribution was assessed by dynamic light scattering (DLS). The relationship between EV size characteristics, including peak diameter, peak height, and interquartile range( IQR), and postoperative coagulation function was analyzed. Results:Compared to patients with normal postoperative coagulation function, those with postoperative coagulation dysfunction had lower size at peak and IQR, and significantly higher peak intensity. Logistic regression analysis indicated that elevated peak intensity and lower size at peak and IQR were risk factors for coagulation dysfunction. The area under the curve ( AUC) for diagnosing coagulation dysfunction with 12 h postoperative EVs peak intensity was 0.76, with a positive predictive value of 85% at the optimal cutoff of 8.2; the AUC for IQR was 0.84, with a sensitivity of 83%, specificity of 82%, and negative predictive value of 86% at the optimal cutoff of 125.05 nm. Conclusion:The size distribution of circulating EVs show a correlation with coagulation function after cardiac surgery with CPB and may serve as a novel biomarker to predict postoperative coagulation dysfunction.
9.Application of CRISPR-based one-pot droplet assay for BK virus nucleic acid detection
Yu LIU ; Jingsong XU ; Min LI ; Hua WANG
Chinese Journal of Laboratory Medicine 2025;48(6):743-749
Objective:To establish a method for quantitative detection of BK virus (BKV) nucleic acid using microfluidic droplet one-pot Recombinase polymerase amplification-clustered regularly interspaced short palindromic repeats, RPA-CRISPR/Cas13a.Methods:A methodology establishment study. Plasma or urine samples were collected from 50 post renal transplant patients and 40 healthy individuals in Renji Hospital, Shanghai Jiao Tong University School of Medicine, from May 16 to August 31, 2024, and the viral genomic DNA was extracted. In the renal transplant group, there were 28 males and 22 females aged (46.1±11.6) years; in the healthy control group, there were 21 males and 19 females aged (45.6±11.3) years. Three crRNAs were designed for screening the optimal crRNA in CRISPR/Cas13a reaction taking PCR product as templet. Two pairs of RPA primers targeting BKV sequences were designed and selected an optimal primer set from four combinations for RPA-CRISPR/Cas13a reaction. Microfluidic droplet generation chip was designed and fabricated for rapid quantitative detection of BKV nucleic acids, which was combined with a droplet reader. BKV plasmid standards were utilized to assess the detection sensitivity of the one-pot assay. The CRISPR droplet one-pot assay and qPCR were utilized to detect the BKV load in the above samples, respectively. The methodological consistency was then analyzed, and Kappa coefficients of the results were calculated using the Kappa test, and the correlation between the two methods was evaluated using linear regression analysis. Results:The RPA-CRISPR/Cas13a reaction system was combined with a droplet chip to establish a CRISPR microfluidic droplet one-pot assay for BKV detection. The sensitivity of the CRISPR microfluidic droplet one-pot assay for detecting BKV was 10 copies/ml, which surpassed that of qPCR (100 copies/ml) without cross-reaction with JC virus. Methodological consistency analysis demonstrated that the Kappa coefficient of the two methods was 0.96, and the coefficient of determination R 2 was 0.95. Conclusion:In this study, a novel BKV detection technology based on the one-pot CRISPR droplet assay was successfully established.
10.Establishment and application of a one-pot lyophilized CRISPR system for detecting CMV in liver transplant recipients
Junheng ZHANG ; Jingsong XU ; Yu LIU ; Haiqian HUANG ; Min LI ; Hua WANG
Chinese Journal of Laboratory Medicine 2025;48(10):1317-1322
Objective:To establish a one-pot lyophilized detection system based on recombinase polymerase amplification (RPA) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas13a) technology for the rapid diagnosis of cytomegalovirus (CMV) infection in liver transplantation recipients.Methods:This study is a methodology study. CRISPR RNA (crRNA) and RPA primers were designed targeting the CMV gene sequence. Optimal RPA primer sets were screened to establish the RPA-CRISPR/Cas13a-based CMV detection system. The limit of detection (LOD) was evaluated using gradient-diluted CMV plasmid standards. Cross-reactivity was assessed using genomic DNA from common opportunistic viruses in organ transplant recipients. Lyophilized reagents were validated with CMV-negative and positive samples. P-values were computed using two-sample t-tests for pairwise comparisons and one-way ANOVA for multi-group analyses to assess fluorescence value differences. Subsequently, lyophilized reagents were employed to detect 22 plasma samples from liver transplantation recipients collected at Renji Hospital, Shanghai Jiao Tong University School of Medicine, from June 3, 2024, to May 31, 2025. The test results were then compared with those obtained using quantitative real-time polymerase chain reaction (qPCR). Consistency between the two methods was evaluated using the Kappa coefficient calculated by Kappa test.Result:The established RPA-CRISPR/Cas13a system achieved a detection sensitivity of 1 copy/reaction and exhibited no cross-reactivity with other common opportunistic viruses in organ transplantation. Lyophilized RPA-CRISPR/Cas13a reagents demonstrated performance equivalent to non-lyophilized reagents. Concordance between lyophilized reagent detection and qPCR results for 22 clinical samples was 100% (22/22).Conclusion:A lyophilized CMV detection method based on RPA-CRISPR/Cas13a technology was successfully developed and validated for convenient diagnosing CMV infection in liver transplant recipients.


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