1.Establishment of a mouse model of chronic renal insufficiency induced by repeated administration of cisplatin
Tongsheng HUANG ; Yun GUO ; Chen YANG ; Ning AN ; Lin YE ; Haoxuan TANG ; Xijie HUANG ; Yongzhi XU ; Qingjun PAN ; Huafeng LIU
Acta Laboratorium Animalis Scientia Sinica 2018;26(1):20-28
Objective To observe the changes of renal tubular injury and the extent of interstitial fibrosis in the C57BL/6 mouse models of chronic kidney disease(CKD),and provide experimental animal evidence for study of the pro-gression of acute kidney injury(AKI)to chronic kidney disease as well as its mechanisms. Methods Twenty-four 8-week-old male C57BL/6 mice were randomly and equally divided into control group, low-dose, medium-dose, and high-dose cisplatin groups,6 mice in each group. Mice in the cisplatin groups were administrated with 5,7 or 10 mg/kg cispla-tin by intraperitoneal injection once a week for 4 weeks. Plasma creatinine and 24-hour urinary protein were detected to as-sess the renal function. The mice were sacrificed, and plasma and kidney samples were collected for subsequent tests. Pathological changes were observed using periodic acid-Schiff(PAS)staining. To evaluate renal tubules injury, the ex-pression of kidney injury molecule 1(KIM-1)was examined by immunohistochemistry and the level of urinary N-Acetyl-β-D-glucosaminidase was detected with a commercial kit. The infiltration of CD3-positive T cells and F4/80-positive macro-phages was observed by immunohistochemistry(IHC)and immunofluorescence. The expression of collagen I and α-smooth muscle actin(α-SMA)were tested by immunohistochemistry to assess the renal fibrosis, while total kidney collagen was detected by Picrosirius red staining. Results In contrast to the normal control group,the kidney injury became more seri-ous in the cisplatin-treated mice as cisplatin concentration increased. Particularly,significant kidney damage was observed in the high-dose cisplatin group. Compared with the control group,the plasma creatinine and 24-hour urinary protein were significantly increased in the high-dose cisplatin group(P<0.05 and P<0.001)indicating impaired renal function. Mor-phologically,numerous clear vacuoles and necrosis were present in renal tubule epithelial cells in the high-dose cisplatin group. The expression of KIM-1 was markedly up-regulated and the level of urinary NAG was elevated. Infiltration of CD3-positive T cells and F4/80-positive macrophages was enhanced in the mice of high-dose cisplatin group. Data from immuno-histochemistry and picrosirius red staining showed that mice of the high-dose cisplatin group developed renal fibrosis evi-denced by markedly up-regulated expression of collagen I and α-SMA. Conclusions Repeated administration of 10 mg /kg cisplatin for 4 weeks can induce chronic renal insufficiency in mice,which may serve as a novel model for the research on underlying mechanisms of progression from acute kidney injury to chronic kidney disease.
2.Progress in clinical application of urgent lung transplantation
Haoxuan LI ; Heng HUANG ; Haoji YAN ; Hongtao TANG ; Xiangyun ZHENG ; Han ZHANG ; Qinchun QIAN ; Kaiyuan JIANG ; Dong TIAN
Organ Transplantation 2021;12(5):539-
Lung transplantation is the only effective treatment of end-stage lung diseases. Nevertheless, shortage of donor lungs has become increasingly prominent worldwide. A large quantity of patients died while waiting for lung transplantation. Urgent lung transplantation is a prioritized allocation strategy for donor lung transplantation according to the urgency of diseases, aiming to shorten the waiting time for donor lungs and reduce the fatality of patients on the waiting list for lung transplantation. However, no consensus has been reached worldwide on the definition, criteria and application of the terminology of urgent lung transplantation. In addition, the survival and net benefits of lung transplant recipients based on this allocation system are still controversial. On the basis of previous clinical research on urgent lung transplantation, the definition criteria, risk factors, survival outcomes, limitations and optimization measures were explicitly elucidated in this article, aiming to provide theoretical reference for comprehensive evaluation of the feasibility of urgent lung transplantation and further optimizing the allocation system of donor lungs.
3.The reliability and validity of the Chinese version of the Edinburgh visual gait score for children with cerebral palsy
Meihuan HUANG ; Qiuxu ZHAO ; Zhen LV ; Ruihao LI ; Haoxuan ZHEN ; Guojun YUN ; Jianguo CAO
Chinese Journal of Physical Medicine and Rehabilitation 2023;45(2):151-156
Objective:To evaluate the reliability and validity of the Chinese version of the Edinburgh visual gait score (EVGS-CN) for children with cerebral palsy.Methods:The EVGS-CN was established following international guidelines for translation and cross-cultural validation of health status questionnaires. Videos of 30 children with cerebral palsy were assessed independently by six raters (with different levels of experience in gait analysis) using the EVGS-CN. Inter- and intra- observer reliability were evaluated using intraclass correlation coefficients (ICCs). The correlation analysis and group comparison were used to test the technique′s criteria-related validity, convergent validity, and discriminant validity.Results:The ICC values of the 17 items in the EVGS-CN ranged from 0.20 to 0.87 for inter-observer reliability, and from 0.41 to 0.90 for intra-observer reliability. Most items showed good inter- and intra-observer reliability among experienced raters, but only a moderate level when used by inexperienced raters. The EVGS-CN results were strongly correlated with those of physician rating scale (PRS) ( r=0.77, P≤0.001) and observational gait scale (OGS) ( r=-0.85, P≤0.001), moderately correlated with the total gross motor function measure-D/E (GMFM-D/E) score ( r=-0.55, P≤0.01), and strongly correlated with 10MWT times ( r=-0.69, P≤0.001) and timed up and go (TUG) times ( r=0.60, P≤0.001). Moreover, significant differences in average EVGS score were found between different gross motor function classification system (GMFCS) levels and between affected limbs on different sides. Conclusion:The EVGS-CN demonstrates satisfactory reliability and validity in evaluating children with cerebral palsy when it is used by an experienced or inexperienced rater.
4.Correlation between triglyceride-glucose index and high on-treatment platelet reactivity during clopidogrel treatment in patients with ischemic stroke
Haoxuan CHEN ; Li YANG ; Zhenzhen LOU ; Yibo ZHAN ; Huiying OUYANG ; Guixian CHEN ; Changlin ZHANG ; Hui MAO ; Xiaojun LI ; Zhiping HUANG ; Zequan ZHENG ; Haoyou XU ; Longlong WEN ; Min ZHAO ; Yuanqi ZHAO
International Journal of Cerebrovascular Diseases 2023;31(4):253-258
Objective:To investigate the correlation between triglyceride-glucose (TyG) index and high on-treatment platelet reactivity (HTPR) during clopidogrel treatment in patients with ischemic stroke.Methods:Patients with ischemic stroke who received maintenance dose of clopidogrel (75 mg/d) in the Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine from January 2017 to March 2021 were retrospectively included. The highest quartile (Q4) of the TyG index was defined as insulin resistance. Platelet reactivity was assessed by thromboelastogram and clopidogrel HTPR was defined as the clot strength induced by adenosine diphosphate (MA ADP) >47 mm. Multivariate regression model was used to analyze the independent correlation between TyG index and platelet reactivity. Results:A total of 83 patients were included. The TyG index showed a linear correlation with MA ADP. The patients were divided into 4 groups according to the quartile of TyG index. The incidence of clopidogrel HTPR increased significantly with the increase of the quartile of the TyG index ( Ptrend=0.017). Multivariate analysis showed that there was a significant independent correlation between insulin resistance and clopidogrel HTPR (odds ratio 4.597, 95% confidence interval 1.285-16.446; P=0.019). Conclusions:In patients with ischemic stroke treated with clopidogrel, the incidence of clopidogrel HTPR gradually increases with the increase of the quartile of the TyG index. The insulin resistance assessed by the TyG index is independently associated with clopidogrel HTPR.
5.Experimental Study on Respiratory Mechanical Parameters of the Patient with Aute Respiratory Distress Syndrome under High Flow Nasal Cannula
Yueyang YUAN ; Li ZHOU ; Xingshuo HU ; Haoxuan HUANG ; Chao HE
Journal of Medical Biomechanics 2022;37(4):E650-E656
Objective T o analyze the influence of high flow nasal cannula (HFNC) on trespiratory mechanical parameters of the patient with acute respiratory distress syndrome (ARDS) based on ventilation experiment, and investigate the therapeutic and side effects of the HFNC. Methods The HFNC ventilation system model based on MATLAB and the physical experiment platform based on active simulated lung ASL5000 were developed to simulate the respiratory movement of ARDS patients with different lung compliance, and a series of the HFNC ventilation experiments were carried out. Both experimental results in MATLAB and physical platform were compared and analyzed. Results The results from the Matlab model-based simulation experiment and physical platform based-physical experiment uniformly showed that increasing the output flow of HFNC would decrease the relevant respiratory mechanical parameters of respiratory flow and tidal volume, but increase the intrapulmonary pressure and the functional residual capacity (FRC). Under the condition of small flow, the output flow from HFNC might be smaller than the inspiratory flow required by the patient, and an inspiratory compensation flow was necessary to make up for the inspiratory flow. Conclusions The necessary reliable compensation flow in inspiration will promote the security of HFNC. Understanding the changes in respiratory mechanical parameters of ARDS patient will be beneficial to pre-evaluate the HFNC, improve the ventilation effect and reduce the ventilation risks.
6.Clinical application of different shimming methods for two-dimensional and three-dimensional T 2 weighted imaging at 7.0 T MR
Xiaoyu WANG ; Song WANG ; Caohui DUAN ; Jianxun QU ; Kun CHENG ; Xiangbing BIAN ; Raphael TOMI-TRICOT ; Linchang LIU ; Yongqin XIONG ; Haoxuan LU ; Jiayu HUANG ; Xin LOU
Chinese Journal of Radiology 2023;57(11):1187-1192
Objective:To evaluate the clinical value of different shimming methods at 7.0 T MR in two-dimensional (2D) and three-dimensional (3D) T 2WI. Methods:Totally 23 healthy volunteers were prospectively recruited from the First Medical Center of PLA General Hospital from November, 2022 to May, 2023, including 12 volunteers who underwent 2D shimming mode and 14 volunteers who underwent 3D shimming mode. 2D shimming mode included patient-specific (PS) mode, direct signal control (DSC) mode, the standard circularly polarized (CP) mode, and volume-specific (VS) mode. 3D shimming mode included universal pulses (UP) mode and CP mode. The image quality for the subtentorial and supratentorial region was assessed by the subjective image quality score and signal-to-noise ratio. Comparisons of quantitative indices between multiple groups were performed using repeated-measures ANOVA or Friedman′s test; comparisons of quantitative indices between 2 groups were performed using paired-samples t test or Wilcoxon signed-rank test. Results:The image quality of subtentorial region and SNR was significant differences in 2D T 2WI with PS mode, DSC mode, CP mode and VS mode ( F=26.74, P<0.001; F=28.24, P<0.001), and the image quality score and SNR of PS mode, DSC mode, VS mode were better than CP mode ( P<0.05). In 2D T 2WI, there was no significant difference in image quality score and SNR of supratentorial region in PS mode, DSC mode, CP mode ( P>0.05). Besides, in 3D T 2WI, the image quality score for subtentorial and supratentorial region of UP mode were better than those of CP mode ( Z=-2.74, P=0.006; Z=-3.24, P=0.001); SNR of subtentorial region was significantly better in UP mode than those in CP mode ( t=3.49, P=0.004). But there was no significant difference in SNR of supratentorial region between the UP mode and CP mode in 3D T 2WI ( P>0.05). Conclusion:T 2WI with different shimming methods at 7.0 T MR can provide data support for the clinical application, which is helpful for the accurate diagnosis of patients with subtentorial lesions.
7.Modeling the noninvasive bi-level positive airway pressure ventilation therapy system and simulated application.
Yueyang YUAN ; Li ZHOU ; Haoxuan HUANG ; Wei LIU ; Xingshuo HU ; Lixin XIE
Journal of Biomedical Engineering 2023;40(2):343-349
Without artificial airway though oral, nasal or airway incision, the bi-level positive airway pressure (Bi-PAP) has been widely employed for respiratory patients. In an effort to investigate the therapeutic effects and measures for the respiratory patients under the noninvasive Bi-PAP ventilation, a therapy system model was designed for virtual ventilation experiments. In this system model, it includes a sub-model of noninvasive Bi-PAP respirator, a sub-model of respiratory patient, and a sub-model of the breath circuit and mask. And based on the Matlab Simulink, a simulation platform for the noninvasive Bi-PAP therapy system was developed to conduct the virtual experiments in simulated respiratory patient with no spontaneous breathing (NSB), chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). The simulated outputs such as the respiratory flows, pressures, volumes, etc, were collected and compared to the outputs which were obtained in the physical experiments with the active servo lung. By statistically analyzed with SPSS, the results demonstrated that there was no significant difference ( P > 0.1) and was in high similarity ( R > 0.7) between the data collected in simulations and physical experiments. The therapy system model of noninvasive Bi-PAP is probably applied for simulating the practical clinical experiment, and maybe conveniently applied to study the technology of noninvasive Bi-PAP for clinicians.
Humans
;
Respiration, Artificial/methods*
;
Positive-Pressure Respiration/methods*
;
Respiration
;
Ventilators, Mechanical
;
Lung
8.Six new coumarins from the roots of Toddalia asiatica and their anti-inflammatory activities.
Haoxuan HE ; Niping LI ; Yunqi FAN ; Qian HUANG ; Jianguo SONG ; Lixia LV ; Fen LIU ; Lei WANG ; Qi WANG ; Jihong GU
Chinese Journal of Natural Medicines (English Ed.) 2023;21(11):852-858
We reported the discovery of six novel coumarins, toddasirins A-F (1-6), each endowed with modified isoprenyl or geranyl side chains, derived from the roots of Toddalia asiatica. Comprehensive structural elucidation was achieved through multispectroscopic analyses, single-crystal X-ray diffraction experiments, and advanced quantum mechanical electronic circular dichroism (ECD) calculations. Furthermore, the anti-inflammatory activity of these compounds was assessed. Notably, compounds 1-3 and 6 demonstrated notable inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells, with 50% inhibitory concentration (IC50) values of 3.22, 4.78, 8.90, and 4.31 μmol·L-1, respectively.
Mice
;
Animals
;
Coumarins/chemistry*
;
Rutaceae/chemistry*
;
Anti-Inflammatory Agents/pharmacology*
;
Plant Extracts/chemistry*
;
RAW 264.7 Cells
;
Nitric Oxide
;
Molecular Structure