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.RBMX overexpression inhibits proliferation,migration,invasion and glycolysis of human bladder cancer cells by downregulating PKM2
Qiuxia YAN ; Peng ZENG ; Shuqiang HUANG ; Cuiyu TAN ; Xiuqin ZHOU ; Jing QIAO ; Xiaoying ZHAO ; Ling FENG ; Zhenjie ZHU ; Guozhi ZHANG ; Hong HU ; Cairong CHEN
Journal of Southern Medical University 2024;44(1):9-16
Objective To investigate the role of RNA-binding motif protein X-linked(RBMX)in regulating the proliferation,migration,invasion and glycolysis in human bladder cancer cells.Methods A lentivirus vectors system and RNA interference technique were used to construct bladder cancer 1376 and UC-3 cell models with RBMX overexpression and knockdown,respectively,and successful cell modeling was verified using RT-qPCR and Western blotting.Proliferation and colony forming ability of the cells were evaluated using EdU assay and colony-forming assay,and cell migration and invasion abilities were determined using Transwell experiment.The expressions of glycolysis-related proteins M1 pyruvate kinase(PKM1)and M2 pyruvate kinase(PKM2)were detected using Western blotting.The effects of RBMX overexpression and knockdown on glycolysis in the bladder cancer cells were assessed using glucose and lactic acid detection kits.Results RT-qPCR and Western blotting confirmed successful construction of 1376 and UC-3 cell models with RBMX overexpression and knockdown.RBMX overexpression significantly inhibited the proliferation,clone formation,migration and invasion of bladder cancer cells,while RBMX knockdown produced the opposite effects.Western blotting results showed that RBMX overexpression increased the expression of PKM1 and decreased the expression of PKM2,while RBMX knockdown produced the opposite effects.Glucose consumption and lactate production levels were significantly lowered in the cells with RBMX overexpression(P<0.05)but increased significantly following RBMX knockdown(P<0.05).Conclusion RBMX overexpression inhibits bladder cancer progression and lowers glycolysis level in bladder cancer cells by downregulating PKM2 expression,suggesting the potential of RBMX as a molecular target for diagnosis and treatment of bladder cancer.
3.RBMX overexpression inhibits proliferation,migration,invasion and glycolysis of human bladder cancer cells by downregulating PKM2
Qiuxia YAN ; Peng ZENG ; Shuqiang HUANG ; Cuiyu TAN ; Xiuqin ZHOU ; Jing QIAO ; Xiaoying ZHAO ; Ling FENG ; Zhenjie ZHU ; Guozhi ZHANG ; Hong HU ; Cairong CHEN
Journal of Southern Medical University 2024;44(1):9-16
Objective To investigate the role of RNA-binding motif protein X-linked(RBMX)in regulating the proliferation,migration,invasion and glycolysis in human bladder cancer cells.Methods A lentivirus vectors system and RNA interference technique were used to construct bladder cancer 1376 and UC-3 cell models with RBMX overexpression and knockdown,respectively,and successful cell modeling was verified using RT-qPCR and Western blotting.Proliferation and colony forming ability of the cells were evaluated using EdU assay and colony-forming assay,and cell migration and invasion abilities were determined using Transwell experiment.The expressions of glycolysis-related proteins M1 pyruvate kinase(PKM1)and M2 pyruvate kinase(PKM2)were detected using Western blotting.The effects of RBMX overexpression and knockdown on glycolysis in the bladder cancer cells were assessed using glucose and lactic acid detection kits.Results RT-qPCR and Western blotting confirmed successful construction of 1376 and UC-3 cell models with RBMX overexpression and knockdown.RBMX overexpression significantly inhibited the proliferation,clone formation,migration and invasion of bladder cancer cells,while RBMX knockdown produced the opposite effects.Western blotting results showed that RBMX overexpression increased the expression of PKM1 and decreased the expression of PKM2,while RBMX knockdown produced the opposite effects.Glucose consumption and lactate production levels were significantly lowered in the cells with RBMX overexpression(P<0.05)but increased significantly following RBMX knockdown(P<0.05).Conclusion RBMX overexpression inhibits bladder cancer progression and lowers glycolysis level in bladder cancer cells by downregulating PKM2 expression,suggesting the potential of RBMX as a molecular target for diagnosis and treatment of bladder cancer.
4.Correlation between lung ultrasound score and adverse prognosis in shock patients in intensive care unit
Zeyu CHEN ; Duanhui LIU ; Xinbo HUANG ; Zhimei GAN ; Yi MO ; Zhenjie LIANG
Journal of Chinese Physician 2023;25(2):232-235,241
Objective:To investigate the correlation of lung ultrasound score and poor prognosis in internal shock patients in intensive care unit (ICU).Methods:The clinical data of 200 shock patients admitted to the ICU of Wuzhou Red Cross Hospital from July 2019 to June 2021 were selected for study. According to the prognosis of patients, they were divided into survival group and death group. The clinical data of shock patients in ICU with different prognosis were analyzed by single factor analysis, multiple factor regression analysis and predictive value analysis.Results:All patients were followed up. The end point of the study was death or transfer from ICU. The follow-up period was 28 days, with a median of 16 days. The 28-day survival rate (OS) of all patients was 62.5%(125/200). The Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, prothrombin time (PT), Fbg, D-dimer(D-D), lactic acid, oxygenation index and lung ultrasound score of the patients in the survival group and the death group were significantly different (all P<0.05), while other indexes were not significantly different (all P>0.05). The results of COX multivariate analysis showed that APACHE Ⅱ score, lactate, and lung ultrasound score were independent prognostic factors of shock patients in ICU (all P<0.05). The survival curves of patients with different lung ultrasound scores were significantly different ( P<0.05). The higher the lung ultrasound score, the lower the 28-day survival rate ( P<0.05). The receiver operating characteristic(ROC) curve analysis showed that the area under curve (AUC), sensitivity and specificity of predicting the prognosis of patients with lung ultrasound score were 0.753, 76.0% and 71.2%, respectively; The AUC , sensitivity and specificity of APACHE Ⅱ score were 0.774, 77.3% and 79.2% respectively; The AUC, sensitivity and specificity of lactic acid were 0.783, 81.3% and 68.8% respectively, with no significant difference (all P>0.05). Conclusions:The lung ultrasound score , lactic acid and APACHE Ⅱ scores are independent risk factors affecting the prognosis of ICU shock patients, and have considerable predictive value.
5.Research on the construction of innovative experimental teaching system of pathogenic biology and immunology
Zhenjie HUANG ; Danying QIU ; Xiuxiu XU ; Shuzeng CHEN ; Lixia CHEN ; Yonghua XIE
Chinese Journal of Medical Education Research 2021;20(4):442-444
Relying on the practice platform of P2 laboratory, researchers reform and explore the contents and forms of experimental teaching for pathogenic biology and immunology, creating an innovative experimental teaching system suitable for training medical students' professional quality and innovative ability. By improving teaching conditions (construction of P2 laboratory), improving teaching methods and innovating experimental teaching contents, and introducing comprehensive design experiment, students' consciousnesses of service and biosafety have been strengthened, meanwhile, their ability to analyze and solve problems has been improved, and their critical and creative thinking has been cultivated.
6.Choice of reoperation for recurrent hepatocellular carcinoma: a study based on propensity score matching
Zhenjie DING ; Huagang LUO ; Yong YANG ; Ke WANG ; Jing HUANG ; Shengdong WU ; Caide LU ; Jiongze FANG
Chinese Journal of Organ Transplantation 2021;42(2):68-74
Objective:The aims of this study were to compare the efficacy between salvage liver transplantation (sLT) and rehepatectomy (RR) basing on the propensity score matching (PSM), and to explore the prognositc factors of patients with recurrent hepatocellular carcinoma (HCC).Methods:124 patients with intrahepatic recurrence after hepatectomy in our center from January 2012 to August 2018 were divided into sLT group( n=46) and RR group( n=78). 34 patients were selected for data analysis base on 1∶1 propensity score matching (PSM). The advantages and disadvantages of the two surgical methods and the prognostic factors of the patients were discussed by comparing the basic clinical data, OS and DFS of the two groups before and after matching. Results:Before matching, the pre-operative serum total bilirubin, the occurrence of multiple tumors, the proportion of preoperative TACE and the proportion of patients within Milan criteria of the sLT group were higher than those of the RR group, and the maximum tumor diameter of the sLT group was shorter than that of the RR group ( P<0.05); the time of operation, the amount of intra-operative blood loss, the positive of MVI and the proportion of postoperative Clavien grade Ⅲ and above of RR group were higher than those of RR group ( P<0.05). After matching, the operation time, intra-operative blood loss and the proportion of postoperative complications of sLT group were higher than those of RR group; there was nosignificant difference between 1-, 3- and 5- years OS of sLT group and RR group( P>0.05), the 1-, 3- and 5-years DFS of sLT group were better than those of RR group( P<0.05); AFP≥100 μg/L was the independent risk factor of OS, and the type of operation and AFP≥100 μg/L were independent risk factors of DFS. Conclusions:The pre-operative condition of sLT group was more severe, and the operation time, intra-operative blood loss and post-operative severe complication rate of sLT group were higher than those of RR group, and the DFS time of sLT group was longer than that of RR group, but there was no significant difference in OS between the two groups.
7.Effect of tea polyphenois on the growth of human papilIomavirus 16 subgenes-immortalized human cervical epithelial cells
Ziyin MO ; Quan CHEN ; Huaping LI ; Xinyue DAI ; Liqian PENG ; Zhonghao YIN ; Jiusui HUANG ; Bihua LIANG ; Runxiang LI ; Zhenjie LI ; Ridong YANG ; Huilan ZHU
Chinese Journal of Dermatology 2018;51(12):892-896
Objective To explore the effect of tea polyphenols on the growth of human papillomavirus 16 (HPV16) subgenes-immortalized human cervical epithelial cells (H8 cells).Methods Cultured H8 cells were divided into 5 groups to be treated with 0 (control group),6.25,12.5,25 and 50 mg/L tea polyphenols respectively for 24,36,and 48 hours,and then cell counting kit-8 (CCK8)assay was performed to detect cell proliferation.After 24 hours of incubation,flow cytometry was conducted to detect cell apoptosis and cell cycle,and fluorescence microscopy to observe the morphology of apoptotic cells.Results After incubation with tea polyphenols at different concentrations for 24,36 and 48 hours,the proliferation of H8 cells was inhibited,and 12.5 mg/L tea polyphenols could inhibit the relative growth rate of H8 cells in a time-dependent manner.Flow cytometry showed that there was a significant difference in cell apoptosis rate among the 6.25-,12.5-,25-,50-mg/L tea polyphenols groups and the control group (52.62% ± 0.62%,52.22% ± 0.72%,42.52% ± 0.90%,45.96% ± 2.11%,29.96% ± 0.70% respectively,F =272.0,P < 0.05).Moreover,all the tea polyphenol groups showed significantly increased cell apoptosis rate compared with the control group (all P < 0.05).Fluorescence microscopy showed karyopyknosis,nuclear fragmentation and other typical apoptotic morphological changes in H8 cells in tea polyphenols groups.There were significant differences in the percentage of cells in G1,G2 phase and cell proliferation index among the 5 groups (all P < 0.05).Compared with the control group,the 6.25-,12.5-,25-mg/L tea polyphenols groups showed significantly increased percentage of cells in G1 phase (55.96% ± 0.72%,54.12% ± 3.20%,65.30% ± 1.51% respectively,all P < 0.05),but significantly decreased percentage of cells in G2 phase (3.17 ± 1.82%,4.94 ± 1.46%,4.65 ± 4.26% respectively,all P < 0.05) and lower cell proliferation index(0.44 ± 0.01,0.46 ± 0.02,0.36 ± 0.01 respectively,all P < 0.05).Conclusion Tea polyphenols can inhibit the proliferation of H8 cells,induce cell apoptosis,and block cell cycle progression.
8.Integrated perinatal management and prognosis of 32 neonates prenatally diagnosed with congenital diaphragmatic hernia
Lin LIN ; Qi CHEN ; Hua HUANG ; Junpeng DU ; Zhenjie CAO ; Xuanxuan CHEN
Chinese Journal of Perinatal Medicine 2018;21(3):175-180
Objective To investigate the integrated perinatal management and prognosis of prenatally diagnosed congenital diaphragmatic hernia (CDH).Methods Clinical data of 32 cases of neonatal CDH that were diagnosed and treated in the Third Affiliated Hospital of Zhengzhou University from June 2015 to June 2017 were collected and retrospectively analyzed.All cases were classified into mild,moderate and severe groups based on prenatal lung-to-head ratio (LHR),observed to expected LHR and observed to expected total fetal lung volume.The integrated perinatal management included prenatal management (prenatal diagnosis and consultation),intrapartum management (delivery) and postnatal management (postnatal diagnosis,neonatal treatment and surgical treatment).Neonatal outcomes were analyzed.Statistical analysis was performed using Chi-square test and t-test.Results All of the 32 cases were diagnosed by prenatal ultrasonography and assessed by MRI.There were 18 mild,nine moderate and five severe CDH cases,respectively.Left-sided and right-sided CDH were respectively found in 27 and five cases.Thirty neonates underwent surgery when the diagnosis had been confirmed after birth and the conditions were stable after comprehensive treatment.The total survival rate was 81% (26/32).The neonatal survival rates of severe and mild groups were 1/5 and 18/18,respectively.The more severe the CDH,the lower the survival rate (x2=16.538,P<0.001).Among the 18 neonates with mild CDH,five neonates underwent minimally invasive laparoscopic surgery had shorter fasting time,duration of postoperative antibiotic administration and hospital stay than those received open surgery (n=13)[(2.4±0.5) vs (4.6±1.2) d,t=-3.939;(7.6±1.2) vs (9.8±1.4) d,t=-3.144;(14.4±1.1) vs (19.7±2.8) d,t=-4.064;all P<0.01].Neonates who were discharged alive received a three months to two years postoperative treatment and follow-up and one received a second operation due to recurrence and all recovered.Conclusions Prognosis of neonatal CDH are closely related to prenatal conditions.Integrated management is of great significance in CDH.
9.Technical specification for clinical application of critical ultrasonography
Wanhong YIN ; Xiaoting WANG ; Dawei LIU ; Yangong CHAO ; Xiangdong GUAN ; Yan KANG ; Jing YAN ; Xiaochun MA ; Yaoqing TANG ; Zhenjie HU ; Kaijiang YU ; Dechang CHEN ; Yuhang AI ; Lina ZHANG ; Hongmin ZHANG ; Jun WU ; Lixia LIU ; Ran ZHU ; Wei HE ; Qing ZHANG ; Xin DING ; Li LI ; Yi LI ; Haitao LIU ; Qinbing ZENG ; Xiang SI ; Huan CHEN ; Junwei ZHANG ; Qianghong XU ; Wenjin CHEN ; Xiukai CHEN ; Daozheng HUANG ; Shuhan CAI ; Xiuling SHANG ; Jian GUAN ; Juan DU ; Li ZHAO ; Minjia WANG ; Song CUI ; Xiaomeng WANG ; Ran ZHOU ; Xueying ZENG ; Yiping WANG ; Liwen LYU ; Weihua ZHU ; Ying ZHU ; Jun DUAN ; Jing YANG ; Hao YANG ; Chinese Critical Ultrasound Study Group ; Gritical Hemodynamic Therapy Collabration Group
Chinese Journal of Internal Medicine 2018;57(6):397-417
Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.
10. Effects of percutaneous nephrolithotomy in the treatment of medullary sponge kidney with calculi
Yang HONG ; Qingquan XU ; Xiaobo HUANG ; Zhenjie ZHU ; Haiyun YE ; Fengshi ZHANG ; Qingya YANG ; Lizhe AN ; Tao XU
Chinese Journal of Surgery 2017;55(10):742-745
Objective:
To evaluate the effects of percutaneous nephrolithotomy (PNL) in the treatment of medullary sponge kidney with calculi.
Methods:
A total of 77 patients (91 renal units) of medullary sponge kidney with calculi (MSK group) and 77 patients (77 renal units) with common kidney stone (control group) received PNL at Department of Urology in Peking University People′s Hospital from September 2006 to February 2016 were analyzed retrospectively. The MSK group included 33 males and 44 females with a mean age of (42.1±13.2) years, the mean stone burden was (3.9±1.8) cm. The control group included 36 males and 41 females with a mean age of (45.3±13.0) years, the mean stone burden was (3.6±1.5) cm. The numbers of tracts, the time of operation, the drop of hemoglobin, the change of creatine, the time of hospitalization, the stone free rate and major complications were compared between the two groups. The measurement data and numeration data were compared with

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