1.Hurthle cell neoplasms in the thyroid gland
Chinese Journal of General Surgery 1994;0(05):-
The comprehensive paper of thyroid Hurthle cell neoplasms(NCNs) is made on the literatures review.This paper reveals the follows:(1)HCNs differ significantly from follicular neoplasms on a molecular level;(2)Clinical and morphological parameters were not helpful in predicting recurrence and in differentiating benign from malignancy neoplasms;(3) The treatment of choice for adenoma is lobo-isthmectomy. For malignant Hurthle cell tumor, total thyroidectomy is the most rational treatment associated with cervical lymphadenectomy in the presence of matastatic nodes. In all cases, long-term periodical follow-up should be done; (4)HCNs represent a pathological entity;(5)The criteria of differentiating adenoma from carcinoma needs further investigation to guide the clinical treatment ;(6)Treatment process of HCNs should be individualized according to the clinical and histopathological results.
2.Effect and mechanism of PCSK9 on lipid homeostasis and cell damage of podocytes
Meiyan WU ; Zhi CHEN ; Chongsen ZANG ; Fuzhe MA ; Jie HOU ; Zhonggao XU
Chinese Journal of Nephrology 2021;37(7):583-590
Objective:To evaluate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on lipid homeostasis and cellular injury of podocytes, and to clarify its mechanism.Methods:Twelve-week old C57BL/6 wild-type mice ( n=10) and PCSK9 knockout ( PCSK9 KO) mice ( n=10) were selected as the animal models. The renal tissues were taken after perfusion through heart. Mouse podocytes were transfected with PCSK9 siRNA to downregulate PCSK9 expression. BODIPY 493/503 staining was performed for evaluating lipid accumulation, and standard transmission electron microscopy (TEM) was used to observe the foot process of podocytes, the shape of mitochondria and lipid droplet in podocytes. TUNEL staining was carried out to evaluate cell apoptosis in glomerulus. The parameters about mitochondria function (key enzymes such as PGC-1α, CPT-1 and Acox-1) and apoptosis were quantified through qPCR and western blotting. Results:The lipid accumulation in glomerulus of PCSK9 KO mice were more serious than controls. The expression of PGC-1α protein and PGC-1α, CPT-1 and Acox-1 mRNA in PCSK9 KO mouse kidney tissues were decreased than controls (all P<0.05), and mitochondria swelling and cristae disappearance in podocytes of PCSK9 KO mice were observed. In PCSK9 KO group, the foot process of podocytes partially fused and disappeared, and the apoptosis index increased compared with the control group ( P<0.05). In vitro, compared with the control group, the lipid accumulation was more significant, transcription level of key enzymes related to mitochondrial function was decreased, mitochondrial structure was damaged and the apoptosis index was increased in cultured podocyte PCSK9 siRNA group (all P<0.05). Conclusions:PCSK9 is involved in the lipid homeostasis of podocytes. The decrease of PCSK9 results in the increase of intracellular lipid accumulation, accompanied by the mitochondrial structure damage and disfunction of podocytes, and leads to cell apoptosis.
3.The role of PCSK9 on lipid accumulation and injury in the kidney of C57BL/6 mice
Meiyan WU ; Chongsen ZANG ; Fuzhe MA ; Bin CHEN ; Weixia SUN ; Mindan SUN ; Hang YUAN ; Zhonggao XU ; Ye JIA
Chinese Journal of Nephrology 2018;34(11):845-850
Objectives To evaluate the role of PCSK9 (proprotein convertase subtilisin kexin type 9) on the lipid accumulation and kidney injury of C57BL/6 mice. Methods The 24 h urine of 12 weeks old wide type C57BL/6 mice and PCSK9 knockout (KO) mice were collected through a metabolic cage, followed by perfusion and sacrifice. Urinary microalbumin?to?creatinine ratio (UACr), total cholesterol and triglyceride in kidney tissues were measured by ELISA. BODIPY 493/503 staining and standard transmission electron microscopy (TEM) of kidney tissues was performed for evaluating lipid accumulation and podocyte foot effacement in the kidney. Kidney tissues were also evaluated by PAS stain and TUNNEL stain. PCSK9, podocin and nephrin were quantified through real?time PCR, and the Bcl?2, Bax and cleaved caspase 3 were evaluated by Western blotting. Results Total cholesterol and triglyceride contents were higher in the kidneys of PCSK9 KO mice than controls (P<0.05). The level of lipid accumulation in glomeruli and tubules through BODIPY 493/503 stain, and the amount of lipid drop in TEM were more serious in PCSK9 KO mice. UACr and podocyte foot process effacement were increased, and the transcription of podocin and nephrin were decreased in the kidneys of PCSK9 KO mice (all P<0.05). The expression of Bcl?2 was decreased, and Bax and cleavedcaspase 3 were increased in the kidney samples of PCSK9 KO mice. Conclusion PCSK9 might be reversely involved in lipid homeostasis and accumulation, resulting in injury and apoptosis in the kidneys of C57BL/6 mice.