1.Effect of silencing Notch1 gene on proliferation, apoptosis and Akt/mTOR pathyway inhibition in clear cell renal cell carcinoma
Zhiming ZHUANG ; Tianqi LIN ; Jiangui LIN ; Minggen YANG ; Hongjie LIU ; Zhouda ZHENG ; Xudong MA
Chinese Journal of Urology 2017;38(2):136-140
Objective To investigate the effect of silencing Notch1 gene by RNA interference on the proliferation,apoptosis and Akt/mTOR signaling pathway in clear renal cell carcinoma.Methods The optimal segment targeting Notch1 gene was designed and transfected into 786-O cells by Lipofectamine TM2000.The Notch1 mRNA and protein were detected by RT-PCR and Western blot.The proliferation rate of 786-O cells was evaluated by MTT and the variation of apoptosis was measured by TUNEL.The protein expression level of apoptosis-related protein Bcl-2,caspase-3,caspase-9,and signaling pathway protein Akt,p-Akt,p-mTOR,p-P70S6K were detected by Western blott.Results Notchl mRNA and protein was markedly suppressed by the siRNA targeting Notch1.Treated with 0,40,60,80,100 and 120 nmol/L of Notch1 siRNA for 24 hours,cell proliferation rates were (98.51 ± 1.33) %,(87.34 ± 2.26) %,(64.72 ± 3.24)%,(57.68 ±3.32)%,(31.91 ± 1.85)% and (19.27 ±2.73)%,and the difference was statistically significant (P < 0.01).Treated with 0,40,80,and 120 nmol/L of Notchl siRNA for 24 hours,apoptosis rates were (7.6 ± 3.8) %,(21.5 ± 4.8) %,(32.3 ± 3.5) %,and (46.3 ± 4.7%),the difference was statistically significant (P < 0.05).Decreased expression of Akt signaling pathway proteins p-Akt,p-mTOR,p-70S6K and apoptosis-related protein Bcl-2,procaspase-3 was detected,but no change in the total protein of Akt.Conclusions Depletion of Notch1 gene could inhibit cell growth and induce apoptosis in 786-O cell line.It inhibits Akt/mTOR signaling pathway by dephosphorylated.
2.The role of the NOD-like receptor thermal protein domain associated protein 3 inflammasome in children with antineutrophil cytoplasmic antibody-associated vasculitis
Jingyi WU ; Lizhi CHEN ; Daojing YING ; Hongjie ZHUANG ; Xiaoyun JIANG
Chinese Journal of Applied Clinical Pediatrics 2022;37(24):1854-1860
Objective:To investigate the role of the NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome and its downstream interleukin(IL)-1β, IL-6, and IL-18 in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis(AAV) in children.Methods:A retrospective study was conducted.Specifically, the localization and expression of the NLRP3 inflammasome in renal tissues of 22 children who were diagnosed with primary AAV and underwent renal biopsy in the Department of Pediatric Nephrology and Rheumatology, the First Affiliated Hospital of Sun Yat-Sen University from September 2003 to September 2020 were detected by the immunohistochemical method.The IL-1β, IL-6 and IL-18 levels in serum and urine were measured by enzyme-linked immunosorbent assay.The measurement data conforming to normal distribution were compared by the t test between two groups and by the single factor ANOVA test among multiple groups.The measurement data that did not conform to normal distribution were compared by the Wilcoxon signed rank sum test.Classification variables were examined by the χ2 test. Pearson correlation coefficient or Spearman rank correlation coefficient were used to analyze the correlation among variables. Results:NLRP3 was widely expressed in the tubulointerstitium, and the expression level in the active group was higher than that in the control group, the semi-quantitative scores of NLRP3 in the renal tubule and glomeruli in the active group were higher than those in the control group ( F=0.859, 8.320, all P<0.05). In the active group, the semi-quantitative score of NLRP3 in the renal tubule was higher than that in the glomeruli( F=3.517, P<0.05). The semi-quantitative score of NLRP3 in the renal tubule was positively correlated with the pediatric vasculitis activity score at renal biopsy ( r=0.471, P=0.027)and negatively correlated with the estimated glomerular filtration rate at renal biopsy ( r=-0.548, P=0.008)in the active group.The serum IL-1β, serum IL-18 and urinary IL-6 levels in the active group were higher than those in the remission group and the control group ( F=16.449, 16.449, 0.637, 29.891, 27.612, 7.464, all P<0.05). The serum IL-18 level in the remission group was higher than that in the control group( F=18.671, P<0.05). In the active group, a positive correlation was found between the serum IL-1β level and the semi-quantitative score of NLRP3 in the renal tubule( r=0.805, P=0.002), between the serum IL-6 level and the C-reactive protein level at renal biopsy ( r=0.728, P=0.017), and between the urinary IL-6 level and the crescent proportion at renal biopsy ( r=0.677, P=0.032). The serum IL-18 level in the active group was positively correlated with the semi-quantitative score of NLRP3 in the renal tubule, pediatric vasculitis activity score and glomerular sclerosis proportion at renal biopsy, and negatively correlated with the estimated glomerular filtration rate at renal biopsy ( r=0.644, 0.612, 0.695, -0.577, all P<0.05). The urinary IL-18 level was positively correlated with the complement C 4 level at renal biopsy ( r=0.855, P<0.05). Conclusions:The NLRP3 inflammasome and its downstream IL-1β, IL-6, and IL-18 may be involved in the pathogenesis and progression of AAV, and can be used as one of the reference indicators for disease activity assessment.
3.Clinical efficacy of hepatic artery infusion chemotherapy combined with immunotherapy plus target therapy in the treatment of advanced hepatocellular carcinoma
Song CHEN ; Wenbo GUO ; Zhiqiang WU ; Wenquan ZHUANG ; Hongjie CAI ; Fan WANG
Chinese Journal of Digestive Surgery 2021;20(S2):32-36
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and the new cases of HCC in China account for more than half of the global cases every year. High incidence mortality and limited treatment methods are the main challen-ges for HCC prevention and treatment in China. Immunotherapy has brought new treatment options and hope of prolonging the survival to patients with advanced HCC. Data from the IMbrave 150 study published in the New England Journal of Medicine in May 2020 showed that the median overall survival of all patients was 19.2 months, and the median overall survival of the Chinese subgroup was 24.0 months, which suggested significant efficacy in prolongating patient survival and controlling tumor. Interven-tional therapy has been playing an important role in the treatment of HCC, and more and more clinical studies have adopted systematic therapy combined with interventional therapy. Interven-tional therapy and systematic therapy have synergistic efficacy which lead to significant clinical efficacy. The authors introduce the diagnosis and treatment of an advanced HCC patient undergoing interventional therapy combined with bevacizumab plus attilizumab treatment, which lead to signifi-cant clinical efficacy of tumor controlling.
4.Advances in the research on the relationship between brown adipose tissue and metabolism in burn and trauma.
Shubo ZHUANG ; Jiake CHAI ; Hongjie DUAN
Chinese Journal of Burns 2014;30(3):251-253
Hypermetabolism and insulin resistance are prominent features of trauma including burn injury, surgery, and infection. Hypermetabolism results in insufficiency in energy supply, which induces organ function lesion, immune suppression, high infection rate, and wound healing delay, thus exerting a strong impact on patients' quality of life and prognosis. The molecular mechanism in the occurrence and development of hypermetabolism is very complicated, and it has not been fully elucidated. Recently, brown adipose tissue (BAT) was found to be present not only in rodents but also in humans, and its activity was associated with resting metabolic rate. BAT may become the new target of research in prevention and control of metabolic disorder.
Adipose Tissue, Brown
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metabolism
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Animals
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Burns
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metabolism
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Energy Metabolism
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Insulin Resistance
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Quality of Life
5.Clinical application and efficacy analysis of castor stent graft in the treatment of aortic diseases
Jiaxiang ZHUANG ; Ren WANG ; Xianlu MA ; Qi XIE ; Zhi DOU ; Fuzhen ZHENG ; Haiyu CHEN ; Yuanxiang CHEN ; Licheng YAN ; Hongjie ZHOU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(2):79-84
Objective:To summarize the use of Castor stent graft in aortic diseases and to analyze their efficacy.Methods:The clinical data of patients with aortic diseases treated with Castor stent graft from November 2017 to August 2022 in Fujian Provincial Hospital were collected and divided into branched stent group and branched stent co-operative group according to the operation method, and the clinical data of both groups were summarized.Results:A total of 75 cases of aortic disease were treated with Castor stents, and finally 53 cases were classified as branched stent group and 22 cases as branched stent co-operative group. The operations in both groups were successful. The median operative time in the branched stent group was 120(100, 160)min, and the median postoperative hospital stay was 7.0(5.5, 10.5)days.There was no postoperative ischemic stroke, no spinal cord ischemia. One case of new aortic dissection occurred. During follow-up, there was one lost case and two deaths, and the rest did not have endoleak, branch stent stenosis, ischemic stroke or re-intervention. In the branched stent co-operative group, there was one postoperative ischemic stroke, one case of slight stenosis of the left subclavian artery stent during follow-up, the remaining cases had satisfactory postoperative outcomes.Conclusion:Castor stent graft is a safe and effective procedure in the treatment of aortic diseases. And Castor stent graft can be used in combination with other endovascular repair techniques in the treatment of complex aortic diseases, with safe and reliable postoperative outcomes.