1.Exploratory study on noninvasive evaluation of renal histopathology by ultrasonic shear wave elastography
Jinyun PU ; Lei YE ; Yonghua HE ; Rongrong XU ; Siying YANG ; Huiqing YUAN ; Siyuan LIU ; Wenpei LIANG ; Liru QIU
Chinese Journal of Nephrology 2023;39(8):587-594
Objective:To determine a relationship between ultrasound shear wave elastography (SWE) and pathological lessions of renal tissues in children with chronic kidney disease (CKD).Methods:It was a cross-sectional observational study, involving children admitted to the Department of Pediatrics of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to December 2021 with definite pathological diagnosis through kidney biopsy. The SWE was used to determine the Young's modulus (elastic modulus) of the cortex and medulla of the upper, middle, and lower poles of the kidney. The renal histopathology was classified or graded. The statistical method was used to analyze the relationship between Young's modulus of the inferior polar cortex (YM cor) and medulla (YM med) of the right kidney and renal pathology. Results:The study included 110 children with definite pathological diagnosis through renal biopsy, aged (10.1±3.4) years old (2-17 years old), with 55 males (50.0%). The body mass index was (20.6±2.4) kg/m 2, and mean arterial pressure was (95±24) mmHg. There were 94 patients (85.4%) with CKD stage 1, 8 patients (7.3%) with CKD stage 2, and 8 patients (7.3%) with CKD stage 3. There was no significant difference of YM cor and YM med in the upper and middle poles of the right kidneys, and YM med in the lower poles of right kidneys in CKD patients with different stages (all P>0.05). Both YM cor [(15.75±3.36) kPa] and YM med [(13.50±2.43) kPa] of CKD stage 3 patients were significantly higher than those of CKD stage 1 patients [(12.94±2.45) kPa, (11.88±2.23) kPa](both P<0.05). There was no significant difference of YM cor and YM med in the lower poles of right kidneys between stage 1 and stage 2 CKD patients (both P>0.05). YM cor[(17.93±3.23) kPa] and YM med [(15.50±1.48) kPa] in patients with crescentic glomerulonephritis were higher than those in patients with focal segmental glomerulosclerosis [(12.71±2.42) kPa, (11.57±2.63) kPa] and mesangial proliferative glomerulonephritis [(12.73±2.04) kPa, (11.48±2.10) kPa](all P<0.05). There was no significant difference of YM cor and YM med between focal segmental glomerulosclerosis and mesangial proliferative glomerulonephritis (both P>0.05). YM cor [(16.30±2.63) kPa] and YM med [(15.54±1.59) kPa] of Lee's Ⅳ grade of IgA nephropathy were higher than those of Lee's Ⅲ grade [(13.32±2.70) kPa, (12.57±2.50) kPa](both P<0.05), while the International Study of Kidney Disease in Children grade of purpura nephritis had no significant correlation with YM cor and YM med (both P>0.05). YM cor [(15.41±2.37) kPa] and YM med [(13.82±2.59) kPa] of interstitial fibrosis/tubular atrophy (T1/T2) group of IgA nephropathy mixed with purpura nephritis were significantly higher than those of T0 group's [(12.99±2.40) kPa, (11.79±2.05) kPa] (both P<0.05). Moreover, crescent formation (C1) group had a higher YM cor [(14.21±2.77) kPa] and YM med [(12.80±2.47) kPa] than those in C0 group [(12.73±2.15) kPa, (11.59±1.97) kPa] (both P<0.05), while YM cor and YM med were unrelated to the mesangial hypercellularity (M), endocapillary cellularity (E), segmental sclerosis or adhesion (S) indicators (all P>0.05). In lupus nephritis patients, YM cor ( r=0.744, P=0.035) and YM med ( r=0.728, P=0.009) were favorably linked with the chronic index, but not with the activity index (both P>0.05). Conclusions:Renal interstitial fibrosis/tubular atrophy and crescentic development are connected with YM cor and YM med at the lower pole of the kidney as measured by SWE. SWE can be used to assess the chronic renal lesions in children with CKD in the early and middle stages. It may develop into a new noninvasive way to assess renal pathology.
2.Protective effect of Qideng Mingmu capsule on retinal vessels in mice with oxygen-induced retinopathy
Chunmeng LIU ; Shan DING ; Xuewen DONG ; Dandan ZHAO ; Siyuan PU ; Li PEI ; Fuwen ZHANG
Chinese Journal of Experimental Ophthalmology 2024;42(5):428-435
Objective:To investigate the effect of Qideng Mingmu capsule on the formation and remodeling of retinal neovascularization in mice with oxygen-induced retinopathy (OIR).Methods:Thirty-six postnatal day 7 (P7)SPF grade C57BL/6J pups were divided into normal group, OIR group, Qideng Mingmu capsule group and apatinib group by random number table method, with 9 mice in each group.The mice in the normal group were raised in normal environment.The mice in the other three groups were fed in hyperoxic environment of (75±2)% oxygen concentration for 5 days from P7 to P12 and then were fed in normal environment for 5 days from P12 to P17 to establish the OIR model.From P12, mice in Qideng Mingmu capsule group and apatinib group were given intragastric administration of Qideng Mingmu capsule (900 mg/kg) and vascular endothelial growth factor receptor 2 inhibitor apatinib (70 mg/kg) respectively, once a day for 5 consecutive days.On P17, paraffin sections of mouse eyeballs were made and stained with hematoxylin-eosin to count the number of vascular endothelial cells that broke through the internal limiting membrane.The retinal slices were prepared and stained with FITC-dextran to quantify the retinal non-perfusion area, neovascularization density and total vascular density.The distribution and fluorescence intensity of retinal vascular endothelial cell marker CD31 and pericyte marker α-smooth muscle actin (α-SMA) were observed by double immunofluorescence staining.Immunohistochemical staining was used to detect the expression and distribution of retinal hypoxia inducible factor-1α (HIF-1α) and vascular endothelial cadherin (VE-cadherin).The use and care of animals were in accordance with the Regulations on the Management of Laboratory Animals issued by the Ministry of Science and Technology.This study was approved by the Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine (No.2019-30).Results:The number of vascular endothelial cells breaking through the internal limiting membrane in normal group, OIR group, Qideng Mingmu capsule group and apatinib group were (2.83±4.40), (37.33±5.43), (23.83±6.79) and (14.00±9.34), respectively, with a statistically significant overall difference ( F=28.313, P<0.001).There were more vascular endothelial cells breaking through internal limiting membrane in OIR group than in normal group, Qideng Mingmu capsule group and apatinib group, showing statistically significant differences (all at P<0.05).In the observation of mouse retinal slices, there were large non-perfusion areas, neovascularization buds and disordered distribution of blood vessels in OIR group.The distribution of blood vessels was more uniform and the areas of non-perfusion and neovascularization were smaller in Qideng Mingmu capsule group and apatinib group than in OIR group.The relative area of central retinal non-perfusion area and neovascularization density were significantly lower in normal group, Qideng Mingmu capsule group and apatinib group than in OIR group (all at P<0.05).The immunofluorescence intensity of CD31 and the absorbance value of HIF-1α were significantly lower, and the immunofluorescence intensity of α-SMA and the absorbance value of VE-cadherin were significantly higher in normal group, Qideng Mingmu capsule group and apatinib group than in OIR group (all at P<0.05). Conclusions:Qideng Mingmu capsule can inhibit retinal neovascularization formation, increase vascular pericyte coverage, relieve retinal hypoxia and increase vascular integrity in OIR mice.It can protect the retinal vessels of OIR mice.