1.Protective effects of myocardium-targeted nanoparticles loaded L-arginineon on sepsis-induced myocardial injury
Zefang PENG ; Ming ZHANG ; Minzhi OUYANG ; Xiangnan OUYANG ; Ganqiong XU ; Jiawei ZHOU ; Meixiang ZHANG
Chinese Critical Care Medicine 2020;32(8):953-959
Objective:To prepare primary cardiomyocyte (PCM) specific peptide-conjugated mesoporous silicon nanoparticles (MSN) with L-arginine (LA) as a core (PCM-MSN@LA), and evaluate its specific protective effect on septic myocardium.Methods:PCM-MSN@LA was prepared by condensation reaction, the characterization of PCM-MSN@LA, the amount of LA modification and release was detected, and the phagocytosis of PCM-MSN@LA and its affinity to myocardial tissue was observed. ① Experiment one: SD neonatal rat cardiomyocytes were divided into control group (Con group), lipopolysaccharide (LPS) group, MSN@LA/LPS group and PCM-MSN@LA/LPS group. The LPS group was stimulated with 5 mg/L LPS for 16 hours, while the MSN@LA/LPS group and PCM-MSN@LA/LPS group were treated with 5 mg/L LPS and 25 mg/L LA-containing nanoparticles (MSN@LA and PCM-MSN@LA) for 16 hours. Cell viability and reactive oxygen species (ROS) production levels were detected. Apoptosis was observed via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method (TUNEL). Western Blot was used to detect the changes in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) proteins. ② Experiment two: 64 healthy male C57BL/6 mice were divided into Sham group, LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group by random number table method, 16 mice in each group. LPS group were injected 50 mg/kg LPS intraperitoneally. MSN@LA/LPS group and PCM-MSN@LA/LPS group were injected with 0.5 mg/kg MSN@LA and PCM-MSN@LA via tail vein immediately after intraperitoneal injection of LPS. Eight animals in each group were used to observe the 24-hour survival rate, and the other 8 mice were used to detect cardiac function by echocardiography at 12 hours after operation; mRNA expressions of interleukin (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) were measured by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR).Results:PCM-MSN@LA was spherical, with particle size of about 180 nm, Zeta potential of about -21 mV, with LA loaded. The amount of LA modification and release rate were 12.3% and 24.3%, respectively. Cell phagocytosis experiments showed that PCM-MSN@LA had the targeting ability of cardiomyocytes and myocardial tissue. Experiment one: after LPS stimulation of myocardial cells, cell viability decreased, while ROS generation, apoptosis, eNOS and iNOS protein expressions increased. Compared with LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group had higher cell viability, reduced ROS levels and apoptosis, increased expressions of eNOS and iNOS. PCM-MSN@LA/LPS group changed the above effect further than MSN@LA/LPS group [cell viability ( A value): 0.51±0.08 vs. 0.41±0.03, ROS (relative fluorescence intensity): 28 450±1 941 vs. 35 628±2 551, TUNEL positive cells/total cells: 0.27±0.03 vs. 0.35±0.04, eNOS/β-Tubulin: 1.467±0.046 vs. 1.201±0.131, iNOS/β-Tubulin: 1.700±0.033 vs. 1.577±0.068, all P < 0.05]. Experiment two: the number of 24-hour survive in MSN@LA/LPS group and PCM-MSN@ LA/LPS group were higher than LPS group (number: 2, 4 vs. 1, P values were 0.36 and 0.03 respectively). Compared with Sham group, the cardiac function of LPS group was significantly inhibited and the mRNA expression of inflammatory factors increased. The PCM-MSN@LA/LPS group had higher left ventricular ejection fraction (LVEF) and left ventricular short-axis shortening rate (LVFS) than LPS group, and lower mRNA expressions of IL-1, IL-6, and TNF-α mRNA [LVEF: 0.456±0.019 vs. 0.337±0.017, LVFS: (21.97±1.78)% vs. (15.53±1.67)%, IL-1 mRNA (2 -ΔΔCT): 169.22±8.95 vs. 189.79±6.79, IL-6 mRNA (2 -ΔΔCT): 19.90±1.60 vs. 23.74±1.45, TNF-α mRNA (2 -ΔΔCT): 8.21±0.81 vs. 11.00±1.48, all P < 0.05]. There was no significant difference in each index between the MSN@LA/LPS group and LPS group. Conclusion:PCM-MSN@LA with myocardial targeting characteristic significantly increased the activity of myocardial cells, down-regulated the expression of inflammatory factors and the production of ROS, alleviated cardiac insufficiency in sepsis, and achieved the targeted treatment of myocardial injury in sepsis.
2.Preoperative ultrasonography of thyroid cancers:is it overdiagnosis or underdiagnosis?
Jiawei LI ; En OUYANG ; Zuofeng LI ; Jin ZHOU ; Kai ZHANG ; Xiaoyan ZHANG ; Cai CHANG
Chinese Journal of Ultrasonography 2018;27(4):308-313
Objective To investigate the accuracy and missed diagnosis rate of preoperative ultrasound in the diagnosis of thyroid carcinoma . Methods With the method of natural language recognition ,816 solitary thyroid nodules which received thyroidectomy were enrolled for the analysis of preoperative ultrasound examination and post-operative pathology results . The accuracy and the rate of missed diagnosis of ultrasonography for the diagnosis of thyroid carcinoma and lymph node metastasis were evaluated with the pathological results as the gold standard . Results There were 783 ( 96 .0% ) malignant thyroid tumors ,6 ( 0 .7% ) follicular tumor with uncertain malignant potential ,and 27 ( 3 .3% ) benign thyroid tumors . Ultrasonography yielded an accuracy of 96 .1% in the differential diagnosis between benign and malignant thyroid nodules and an accuracy of 94 .5% in the quantification of nodule numbers . 5 .5% of solitary nodules reported by ultrasound were proved to be 2 or more malignant nodules after the surgery . Regarding the diagnosis of central lymph node ,the preoperative ultrasound yielded an accuracy of 73 .0%and a misdiagnosis rate of 38 .7% . For the lateral neck lymph node ,the accuracy was 88 .3% ,and the misdiagnosis rate was 3 .4% . Conclusions Natural language recognition method can assist clinical research . Ultrasonography is valuable in the diagnosis of thyroid carcinomas and neck lymph nodes . However , ultrasonography has a certain rate of misdiagnosis for the quantification of nodule numbers ,and for the diagnosis of lymph nodes in central and lateral necks .
3.Epidemiological characteristics of traumatic spinal cord injury in China in 2018
Dingjun HAO ; Baorong HE ; Liang YAN ; Jinpeng DU ; Xiao QI ; Shicheng YU ; Jiaojiao ZHANG ; Wenjing ZHENG ; Rongqiang ZHANG ; Dageng HUANG ; Junsong YANG ; Ming ZHU ; Jiawei OUYANG ; He ZHAO ; Keyuan DING ; Haodong SHI ; Yang CAO ; Ying ZHANG ; Qinghua TANG ; Yuan LIU ; Zilong ZHANG ; Yuhang WANG ; Ye TIAN ; Hao CHEN ; Lulu BAI ; Heng LI ; Chenchen MU ; Youhan WANG ; Xiaohui WANG ; Chao JIANG ; Jianhua LIN ; Bin LIN ; Shunwu FAN ; Lin NIE ; Jiefu SONG ; Xun MA ; Zengwu SHAO ; Yanzheng GAO ; Zhong GUAN ; Yueming SONG ; Weihu MA ; Qixin CHEN
Chinese Journal of Trauma 2021;37(7):618-627
Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions,9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury,injury level,severity of injury,segment and type of fracture,complications,death and other data were collected by medical record questionnaire,and analyzed according to geographical region,age and gender.Results:Medical records of 4,134 patients were included in this study,with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million (95% CI 50.122-50.846). The highest incidence in the Eastern region was 53.791 / 1 million (95% CI 53.217-54.365). In the whole country,the main causes of injury were high falls (29.58%),as well as in the Western region (40.68%),while the main causes of injury in the Eastern and Central regions were traffic injuries (31.22%,30.10%). The main injury level was cervical spinal cord in the whole country (64.49%),and the proportion of cervical spinal cord injury in the Central region was the highest (74.68%),and the proportion of lumbosacral spinal cord injury in the Western region was the highest (32.30%). The highest proportion of degree of injury was incomplete quadriplegia (55.20%),and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation,77.95% in the Western region and only 54.77% in the Central region. In the whole country,the head was the main combined injury (37.87%),as well as in the Eastern and Central regions,while the proportion of chest combined injury in the Western region was the highest (38.57%). A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients (0.56%) died in hospital,of which 17(73.91%) died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level,incomplete quadriplegia as the main degree of injury,head as the main combined injury,and respiratory complications as the main complication.
4.Targeting a novel inducible GPX4 alternative isoform to alleviate ferroptosis and treat metabolic-associated fatty liver disease.
Jie TONG ; Dongjie LI ; Hongbo MENG ; Diyang SUN ; Xiuting LAN ; Min NI ; Jiawei MA ; Feiyan ZENG ; Sijia SUN ; Jiangtao FU ; Guoqiang LI ; Qingxin JI ; Guoyan ZHANG ; Qirui SHEN ; Yuanyuan WANG ; Jiahui ZHU ; Yi ZHAO ; Xujie WANG ; Yi LIU ; Shenxi OUYANG ; Chunquan SHENG ; Fuming SHEN ; Pei WANG
Acta Pharmaceutica Sinica B 2022;12(9):3650-3666
Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.