1.Treatment of idiopathic membranous nephropathy in 35 children
Haiyun GENG ; Yong YAO ; Jiyun YANG ; Fang WANG ; Xiaoyu LIU ; Xuhui ZHONG ; Huijie XIAO
Chinese Journal of Applied Clinical Pediatrics 2016;31(5):341-344
Objective To investigate the prognosis and efficiency of glucocorticoid and immunosuppressor in the treatment of idiopathic membranous nephropathy(IMN)in children. Methods A retrospective analysis of 35 cases of biopsy - proven membranous nephropathy without secondary factors was performed,who were found present with ne-phrotic proteinuria and admitted to hospital from March 2004 to July 2013,to explore the efficiency of treatment with glucocorticoid and immunosuppressor and its prognosis. Results The 35 IMN cases included 18 boys and 17 girls,and the ratio was 1. 1∶ 1. 0. The mean age at onset was(11. 3 ± 0. 5)years with a range of 3. 0 - 17. 1 years. Five cases with gross hematuria,24 cases present with microscopic hematuria,8 cases with hypertension,1 case with chronic renal insufficiency,and 2 cases were complicated with thrombosis. According to membranous nephropathy staging criteria,9 cases(25. 7% )were in stage Ⅰ,16 cases(45. 7% )in stage Ⅱ,10 cases(28. 6% )in stage Ⅲ;about 94. 3%(33 / 35 cases)had mesangial cells and mesangial matrix with mild to moderate hyperplasia. They were all treated with glucocor-ticoid initially and one of them showed sensitive to flucocorticoid but developed flucocorticoid resistance after relapse, while all the others were flucocorticoid - resistant. Cyclophosphamide A(CsA)was introduced to 17 cases and at least lasted for 3 months,in which 13 cases(76. 5% )reached complete remission and 3 cases reached partial remission, while 1 case didn't achieve remission,and the mean time for proteinuria to disappear was(4. 9 ± 3. 7)months;5 cases were treated with Mycophenolate mefetil( MMF),among which 4 cases reached complete remission in 2 months,4 months,5 months,and 9 months separately,while 1 case reached partial remission. Cyclophosphamide(CTX)was intro-duced to 6 cases,in which the mean cumulative dosage was(91. 2 ± 46. 5)mg/ kg,among them 1 case(87 mg/ kg) reached complete remission,1 case(160 mg/ kg)partial remission,but 4 cases didn't achieve remission. One case reached remission after Rituximab(RTX)was introduced. One case got partial remission after Leflunomide(LEF)was introduced,and the complete remission rate was higher in those treated with combined therapy of glucocorticoid and CsA than those treated with glucocorticoid only(76. 5% vs 12. 5% ,P = 0. 004),but the total efficacy showed no difference (94. 2% vs 62. 5% ,P = 0. 081). The complete remission rate(76. 5% vs 38. 5% ,P = 0. 042)and total efficacy (94. 1% vs 61. 5% ,P = 0. 040)were higher in those with combined therapy of steroid and CsA than those treated with steroid and other immunosuppressor. The complete remission rate(76. 5% vs 16. 7% ,P = 0. 018)and total efficacy (94. 1% vs 33. 3% ,P = 0. 008)were also higher than those treated with steroid and CTX,but the complete remission rate(76. 5% vs 80. 0% ,P = 0. 687)and total efficacy(94. 1% vs 100. 0% ,P = 0. 773)showed no difference com-pared with those treated with steroid and MMF. Conclusions IMN shows glucocorticoid resistance mostly,while CsA had definite efficiency and may be better than CTX. And the efficiency of MMF should be noted.
2.S100A10 promotes proliferation and invasion of lung adenocarcinoma cells by activating the Akt-mTOR signaling pathway.
Huijie WANG ; Zhengui SUN ; Wenying ZHAO ; Biao GENG
Journal of Southern Medical University 2023;43(5):733-740
OBJECTIVE:
To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.
METHODS:
Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.
RESULTS:
The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).
CONCLUSION
S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.
Animals
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Mice
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Adenocarcinoma of Lung/pathology*
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Cell Proliferation
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Lung Neoplasms/pathology*
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Mice, Nude
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Proto-Oncogene Proteins c-akt
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Signal Transduction
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TOR Serine-Threonine Kinases
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Humans
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S100 Proteins/genetics*
3.Relationship between zinc finger protein A20, CTGF and FibroScan and fibrosis in chronic hepatitis B patients
Song ZHANG ; Zilong ZHAO ; Qian HU ; Jian LI ; Xiaojing WANG ; Huijie GENG ; Haiyan KANG ; Dianxing SUN ; Zhengrong GUO
Journal of Public Health and Preventive Medicine 2024;35(3):133-136
Objective Studies on the expression and location of zinc finger protein A20 (A20) and connective tissue growth factor (CTGF) in liver tissues of patients with chronic hepatitis B were conducted, and the relationship between them and liver fibrosis was determined by FibroScan. Methods Studies on A20 and CTGF in liver tissues of 160 patients with chronic hepatitis B were conducted in accordance with the stage of pathological fibrosis and inflammation of the liver, and quantitative immunohistochemistry test was conducted, and statistical analysis was conducted by FibroScan. Results The expressions of A20 and CTGF in liver tissues increased with the aggravation of liver pathological fibrosis and inflammation, and there were significant differences between each stage and the control group (P<0.05), and there were significant differences between adjacent groups (P<0.05). Studies have shown that FibroScan increases along with pathological fibrosis and inflammation in the liver. There are significant differences between the stage and the control group (P<0.05), and no significant differences between the adjacent groups (P>0.05). There was positive correlation between liver A20 and CTGF, r=0.796 (P<0.05). Conclusions In patients with chronic hepatitis B, A20, CTGF and FibroScan are positively correlated with the degree of liver fibrosis, and A20 and CTGF are also positively correlated with the degree of liver inflammation, which can be used as indicators to evaluate the degree of liver inflammation and fibrosis, and further guide the anti-inflammatory and anti-fibrosis treatment of patients.