1.Validation of the Oxford classification for pediatric IgA nephropathy
Huijuan ZHANG ; Qingyin GUO ; Wensheng ZHAI ; Xianqing REN ; Ying DING ; Xiaoqing YANG
International Journal of Pediatrics 2013;40(5):532-534,537
Objective To assess the validity of the Oxford classification for pediatric patients with primary IgA nephropathy (IgAN) and to analyze the correlations between clinical characteristics at time of biopsy and the Oxford classification,which identified four definitive histological features:mesangial hypereellularity,endocapillary proliferation,segmental sclerosis and tubular atrophy/interstitial fibrosis.Methods Clinical and pathological characteristics of 35 children with primary IgAN were analyzed.The scoring sheet was based on the Oxford classification of IgAN,and four pathological variables,namely mesangial hypercellularity (M),endocapillary proliferation (E),segmental sclerosis (S),and tubular atrophy/interstitial fibrosis (T) were assessed.A total of 35 children with IgAN were grouped according to the scores(M,E,S,T):the M0 and M1 group,E0 and E1 group,S0 and S1 group,T0 and T1/T2 group.These groups were compared in terms of estimated glomeralar filtration rate (eGFR),mean artery pressure (MAP) and proteinuria at time of biopsy.Results We found that the Oxford classification was significantly negatively correlated with eGFR (Pearson's correlation coefficient r =-0.48).However,the Oxford classification was shown to be positively associated with initial proteinuria per day(Pearson's correlation coefficient r =0.35).The M,E,S,T scores were strongly associated with proteinuria at biopsy (P < 0.05),and the lesion S was not correlated with eGFR (P > 0.05).The lesion T was significantly associated with eGFR (P =0.001) and MAP (P =0.03) at biopsy.Conclusion We confirmed that the Oxford classification of IgA nephropathy was valid for children.In addition,our study indicated that the four histological lesions M,E,S and T were significantly associated with clinical features.
2.Research Progress of Henoch-Schonlein Purpura Experimental Animal Model Based on the Combination of Disease and Syndrome
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(12):3955-3960
Henoch-Schonlein purpura(HSP)combination of disease and syndrome model has short modeling time,strong operability and high repeatability,which is more suitable for the research of TCM and integrated traditional Chinese and Western medicine.However,there are still the following deficiencies:①Lack of model evaluation criteria.What criteria should be used to establish successful animal models and whether the diagnostic criteria for human HSP are of reference significance?In the future,we should cooperate with Chinese veterinary medicine to carry out omics studies at various levels including genome,proteome and metabolome by combining the unique information of animals with the theories and methods of systems biology,and formulate the criteria for determining HSP animal models through data integration.In terms of syndrome:all the existing models are the model of animal stasis and heat syndrome caused by gavage of heat-induced drugs,but there is no criterion for the successful establishment of syndrome.In the future,it can be combined with ethanol,high-fat diet and fatty milk on the basis of simple heat-induced drug gavage,and compare different combination groups.In the aspect of syndrome evaluation,the four-diagnosis quantitative syndrome differentiation system was introduced to establish the TCM syndrome model evaluation scale of Henoch-Schonlein Purpura's stasis and heat.② There are great differences between animal model and clinical practice,and the reproducibility is low.At present,the combined models of disease and syndrome focus on purpura nephritis,and in the establishment of the animal model of pure dermal allergic purpura,the skin damage rate of the animal model(such as purpura,purpura)is low.In the future,we can learn from the modeling method of other allergic diseases,and increase the excitation times in the operation steps,in order to improve the skin damage rate.③All the existing HSP models are the syndrome model of blood stasis and heat first,and the disease model of HSP is reconstructed.However,the actual disease occurrence is the syndrome in the disease,and the syndrome is the pathological summary at a certain stage in the development of the disease,which is dynamic.In the future,the intervention operation of the etiology and syndrome should be carried out on experimental animals at the same time,so as to build a stable time window for the combination of disease and syndrome.
3.The clinical and pathological features of capillary proliferative purpura nephritis in 19 children
Chundong SONG ; Ying DING ; Zonggang ZHAI ; Wensheng ZHAI ; Xianqing REN ; Qingyin GUO ; Xia ZHANG ; Meng YANG ; Jian ZHANG
Journal of Clinical Pediatrics 2016;34(6):414-417
Objective To explore the clinical and pathological features, treatment, and prognosis of capillary proliferative purpura nephritis (DEP-HSPN) in children.MethodsThe clinical data of 19 children diagnosed with DEP-HSPN were retrospectively analysis. Fifty-five children diagnosed with HSPN by renal biopsy were randomly selected as control group. ResultsThe average age was 10.6±2.6 years old, and the average course of disease were 19.4±7.4 days before renal biopsy in 19 children with DEP-HSPN (14 males and 5 females) who make up 3.92% of anaphylactic purpura nephritis children conifrmed by renal biopsy in the same period. In these 19 children, there were 10 cases having nephrotic syndrome and 9 case having hematuria and proteinuria type, all of whom were received immunosuppressive therapy. Finally, 14 cases achieved completely remission and 5 cases had partly remission. All of their classiifcations of renal pathology wereⅢb levels, accompanied with 6.38% to 36.36% of crescents. Compared with 55 age and sex matched children with renal pathology classiifcation ofⅢb, the DEP-HSPN children had shorter disease course, higher level of proteinuria, and lower pathological score of chronic renal injury (P all?0.05). There was similar percentage of crescent between two groups.ConclusionsChildren with DEP-HSPN usually have rapid onset, severe clinical manifestations, more active lesions and less chronic lesions. There is no evidence that the capillary proliferative lesion is a risk factor in the prognosis of HSPN so far.
4.Characteristics of Syndrome Differentiation and Immune Imbalance in Children with Atopic Dermatitis
Panpan ZHAI ; Yanjie HUANG ; Xiaofeng MEI ; Jiajia LI ; Xiumin LI ; Xia ZHANG ; Wensheng ZHAI ; Xianqing REN ; Ying DING ; Chenhong XUE ; Ge QIAN ; Mingsan MIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(6):2168-2173
Objective To investigate the syndrome differentiation characteristics of children with atopic dermatitis(AD)and the immune imbalance status in children with different syndrome types of AD.Methods A total of 159 AD children and 100 normal control children were enrolled.The peripheral blood eosinophil(Eo)count was measured by impedance method,total serum immunoglobulin E(IgE)by immunoturbidimetric assay,and interferon-gamma(IFN-γ),interleukin-4(IL-4),interleukin-5(IL-5)and interleukin-17(IL-17)were measured by multiple microspheres flow immunofluorescence assay.Results Among 159 AD children,syndrome of heart-fire and spleen-deficiency was most commom,accounting for 38.4%,followed by syndrome of blood-deficiency and wind-dryness(22.0%),syndrome of heat accumulation in heart and spleen(20.1%)and syndrome of spleen-deficiency and dampness-accumulation(19.5%).Compared with normal control group,there was no significant difference in serum IFN-γ level among different syndrome types of AD.The levels of peripheral blood Eo,serum total IgE,IL-4 and IL-17 in AD with heart-fire and spleen-deficiency syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo,IL-4,IL-5 and IL-17 in AD with blood-deficiency and wind-dryness syndrome were significantly increased(P<0.05).The levels of IL-4,IL-5 and IL-17 in AD with heat accumulation in heart and spleen syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo and serum IL-4 in AD with spleen-deficiency and dampness-accumulation syndrome were significantly increased(P<0.05).Conclusion Heart-fire and spleen-deficiency syndrome is the most common type in children with AD,however,the main type under 3 years old is heat accumulation in heart and spleen syndrome.Th2/Th17 immune imbalance are the main pathogenesis in heart-fire and spleen-deficiency syndrome,blood-deficiency and wind-dryness syndrome and heat accumulation in heart and spleen syndrome,and Th2 immune imbalance is the main pathogenesis of spleen-deficiency and dampness-accumulation syndrome.
5.Discussion on the Pathogenesis and Treatment of Children Enuresis Based on the Theory "Kidney-Marrow-Brain" Axis and "Yin Heel Channel (阴跷脉)"
Bo ZHANG ; Xianqing REN ; Wen FU ; Yuying SUN ; Xiaoyu LIU ; Chundong SONG ; Xia ZHANG ; Qingyin GUO ; Ying DING
Journal of Traditional Chinese Medicine 2024;65(9):909-914
Guided by the theory of "kidney generates marrow", the study elaborates the viewpoint that the route of Yin Heel Channel (阴跷脉) is consistent with the "kidney-marrow-brain" axis from the perspective of the circulation of the meridians and the relationship between the zang-fu organs. Accordingly, it is believed that disease of Yin Heel Channel and dysfunction of the "kidney-marrow-brain" axis are the core pathogenesis of children enuresis, and it is elaborated from the following three major aspects, firstly, insufficient kidney essence, dysfunction of the "kidney-marrow-brain" axis, secondly, disease of Yin Heel Channel and deficiency and cold in lower jiao, and thirdly, disease of Yin Heel Channel and loss of nourishment of Chong Vessel. It is proposed to use the mode of "firstly needle, secondly moxibustion, and lastly consolidation" to treat children enuresis. Needle is to adjust yin and yang, warm yang and tonify kidney, and wake up the brain and open the orifices. The acupoints in Yin Heel Channel such as Zhaohai (KI 6), Jiaoxin (KI 8) and confluence points of the eight extraordinary vessels such as Waiguan (TE 5), Zulinqi (GB 41) are used, together with Baihui (GV 20), Yintang (EX-HN 3), Guanyuan (CV 4), Qixue (KI 13), Dazhong (KI 4). Moxibustion is to reinforce healthy qi and warm yang, bank up the root and consolidate the original qi by moxibustion at Shenque (CV 8), Mingmen (GV 4), and Xuanshu (GV 5). Consolidation is to use acupoints application to consolidate the therapeutic effect, and Guanyuan (CV 4) & Pangguangshu (BL 28), Qihai (CV 6) & Zhishi (BL 52), and Shenque (CV 8) & Ciliao (BL 32) are commonly used as the three groups of acupoints to warm the kidney and stop collapse, regulate and tonify the qi and blood.
6.Effect of Tripterygium wilfordii Polyglycoside on Expression of NFAT2/COX-2 in Kidney Tissues of Rats with Diabetic Nephropathy
Fengyang DUAN ; Chundong SONG ; Dan SONG ; Ying DING ; Xianqing REN ; Xia ZHANG ; Wensheng ZHAI ; Ting GUO ; Yaoxian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):16-23
ObjectiveTo explore the underlying mechanism of Tripterygium wilfordii polyglycoside tablets (TWPT) in the prevention and treatment of kidney injury in diabetic nephropathy (DN) through the nuclear factor of activated T-cells 2(NFAT2)/cyclooxygenase-2(COX-2) pathway. MethodForty-two male SD rats of SPF grade were selected and randomly divided into a normal group (n=8) and an experimental group (n=34) after one week of adaptive feeding. The rats in the normal group were fed conventionally. The DN model was established in rats of the experimental group by intraperitoneal injection of streptozotocin (STZ) following one week of feeding on a high-fat and high-glucose diet. After the death and failure cases during modeling were eliminated, the remaining 24 model rats were randomly divided into model group, valsartan (8.33 mg·kg-1·d-1) group, and TWPT (5 mg·kg-1·d-1) group. Rats in normal group and model group were given equal amounts of normal saline by gavage. After six weeks, body weight was measured and urine samples were collected. Blood samples were collected from the abdominal aorta, and then the rats were sacrificed for sampling. Biochemical indicators, such as serum blood urea nitrogen (BUN), serum creatinine (SCr), alanine aminotransferase (ALT), blood lipid, blood glucose, and 24-hour urine total protein (24 h UTP), were determined. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathology of the kidney. Enzyme-linked immunosorbent assay (ELISA) was used to detect NFAT2 and COX-2 expression levels in the serum. Western blot and Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)were adopted to detect NFAT2, COX-2 protein and mRNA expression in kidney tissues, respectively. ResultCompared with the normal group, the model group showed elevated 24 h UTP, BUN, SCr, CHO, TG, and FBG, increased serum NFAT2 and COX-2 production and expression (P<0.01), and elevated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues (P<0.01). In addition, the pathology of the kidney showed enlarged glomeruli, mild proliferation of mesangial cells, and widened mesangial stroma. Compared with the model group, the TWPT group showed decreased 24 h UTP, BUN, SCr, CHO, TG, and FBG (P<0.05,P<0.01), basically normal glomerular morphology, decreased expression of serum NFAT2 and COX-2 (P<0.01), and down-regulated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues (P<0.01). ConclusionTWPT can alleviate 24 h UTP in DN model rats, protect renal function, and improve renal pathology, and its mechanism of action may be related to the down-regulation of NFAT2/COX-2 expression in the serum and kidney tissues.
7.Effect of Yiqi Yangyin Huoxue Prescription on NLRP3/Caspase-1/GSDMD Pyroptosis Pathway in Diabetic Kidney Disease Rats
Pingping JIA ; Chundong SONG ; Fengyang DUAN ; Ningli WANG ; Ying DING ; Yaoxian WANG ; Xianqing REN ; Wensheng ZHAI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):75-81
ObjectiveTo explore the possible mechanism of Yiqi Yangyin Huoxue prescription in the prevention and treatment of kidney injury of diabetic kidney disease(DKD)rats based on NOD-like receptor protein 3(NLRP3)/cysteine protease-1(Caspase-1)/gasdermin D (GSDMD)pyroptosis pathway. MethodFifty male SD rats were randomly divided into normal group (n=8) and modeling group (n=42). The modeling group was given a one-time intraperitoneal injection of streptozotocin (STZ) after high-sugar and high-fat diet for 6 weeks to induce the establishment of a DKD rat model. After successful modeling, the rats were randomly divided into model group, valsartan group (8.33 mg·kg-1), and Yiqi Yangyin Huoxue prescription low-dose and high-dose group (11,22 g·kg-1). After continuous gavage for 6 weeks, the fasting blood glucose (FBG), total cholesterol (CHO), triglyceride (TG), blood urea nitrogen (BUN), serum creatinine (SCr) and 24-hour urine protein quantification (24 h-UTP) were detected in each group of rats. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of kidney tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels. The protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue of rats in each group were determined by Western blot and real-time quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the conditions in normal group, the levels of FBG, CHO, TG, BUN, SCr, 24 h-UTP and serum IL-1β and IL-18 as well as the protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue in model group were increased (P<0.01), and the kidney tissue lesions were severe. Compared with the conditions in model group, the levels of FBG, CHO, TG, BUN, SCr, 24 h-UTP and serum IL-1β and IL-18 as well as the protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue in each intervention group were decreased (P<0.05, P<0.01), and the degree of kidney tissue lesions was improved, with Yiqi Yangyin Huoxue prescription high-dose group showing the optimal effect. ConclusionYiqi Yangyin Huoxue prescription could inhibit pyroptosis by regulating the NLRP3/Caspase-1/GSDMD pathway, and thus relieve the inflammatory response of DKD rats and alleviate the pathological damage of the kidneys.