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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.
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Objective To investigate the diagnostic value of ultrasound ADNEX model in ovarian tumors.Methods 226 patients with pathological-confirmed ovarian tumor from Jun.2014 to Jun.2018 were selected,and the preoperative ultrasound imaging,clinical and pathological data were analyzed.The ultrasound imaging was recorded,and ovarian tumor was diagnosed through ADNEX model.The diagnostic efficiency of ADNEX model for ovarian benign and malignant tumors was analyzed with pathological findings as the gold standard.Results The differences of onset age,CA125 level,tumor solid components maximum diameter and ratio,＞10 locules and ascites were all statistically significant between each ovarian tumor group (P＜0.05).The overall accuracy rate of ADNEX model in diagnosing different ovarian tumors was 83.2％,which has a good consistency with histopathological findings (Kappa=0.782,P＜0.05).The sensitivity and specificity of the prediction model in predicting benign,borderline,stage Ⅰ,stage Ⅱ-ⅣV and metastatic ovarian tumor were respectively 85.5％ and 95.7％,69.2％ and 96.0％,81.6％ and 93.8％,89.1％ and 94.4％,80.0％ and 98.5％.Conclusion Ultrasound ADNEX model is helpful in differential diagnosis of benign and malignant ovarian tumor,and it has important significance for clinical treatment and prognosis evaluation.
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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.
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Objective To investigate the correlation between the blood flow characteristics of contrastenhanced ultrasound (CEUS) and malignancy of patients with ovarian tumor.Methods 60 cases with ovarian tumors treated by surgery and confirmed by pathology were selected,including 28 cases of ovarian cancer and 32 cases of benign ovarian tumor.The time of arrival (AT),peak time (TTP) and intensity of enhancement (EI) were determined by CEUS,and microvessel density (MVD) of tumor tissue was detected by immunohistochemistry.The correlation of the above parameters with MVD and tumor staging was analyzed.Results AT,TTP of the malignant tumor group (10.8±2.1,25.3±10.5) was significantly lower than those of the benign tumor group (15.4±2.7,59.4±11.2).EI of the malignant tumor group (28.6±2.9) was significantly higher than that of the benign tumor group (14.9±2.6),with statistical significance (P＜0.05).MVD of the malignant tumor group (62.8± 13.6) was significantly higher than that of the benign tumor group (21.5±11.4),with significant difference (P＜0.05).AT and TTP were negatively correlated with MVD and FIGO staging (r=-0.562,r=-0.504,r=-0.636,r=-0.623),while EI was positively correlated with MVD and FIGO staging (r=0.839 and r=0.785),with statistical difference (P＜0.05).Conclusions Blood flow characteristics of CEUS are closely related to the malignancy of ovarian tumors.CEUS can accurately evaluate angiogenesis,blood perfusion and malignancy of ovarian tumors.
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Objective To investigate the correlation of serum concentration of B vitamins B1,B6,B12) with the incidence of epilepsy.Methods We recruited 50 newly diagnosed patients with epilepsy (not receiving antiepileptic drugs) and 50 patients without epilepsy.Serum concentrations of B vitamins (B1,B6,and B12) in both groups were detected with a LK3000V vitamin detector.Results The concentrations of vitamin B1 and B12 in epileptic patients were (132.81 ±7.3l) nmol/L and (221.41 ±26.09) pg/ml,respectively,not significantly different from those in non-epileptic patients [(130.44 ± 5.12) nmol/L,P =0.095 ;(197.87 ± 19.36) pg/ml,P =0.077].The concentration of vitamin B6 in epileptic children was (44.61 ±2.49) μmol/L,significantly lower than that in non-epileptic children [(64.63 ± 5.71) μmol/L,P =0.031].Conclusion Though serum concentrations of vitamin B1 and B12 may not be associated with epilepsy,lower concentration of vitamin B6 in serum may increase the risk of epilepsy.
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Objective To assess the efficacy and safety of lanthanum carbonate in treatment of hyperphosphatemia in end-stage renal disease (ESRD).Methods Randomized controlled trails of lanthanum carbonate in treatment of hyperphosphatemia in ESRD patients were searched in the database of MEDLINE,Cochrane Central Register of Controlled Trials,EMBASE,CNKI,Wanfang database.Data extracted from the literatures were analyzed with the Cochrane Collaboration's RevMan 5.1 software.Results Lanthanum carbonate group was similar with calcium carbonate group in treating hyperphosphatemia[RR =1.00,95 ％ CI (0.92-1.09),P =0.97],and more effective than placebo [RR=4.69,95％ CI (2.63-8.39),P＜ 0.01] (intervention dose≤ 1500 mg) and [RR =18.92,95％ CI (7.42-48.22),P ＜ 0.01] (intervention dose ＞ 1500 mg).In comparison with calcium carbonate group,the incidence of hypercalcinemia of lanthanum carbonate group was lower [RR =0.06,95 ％ CI (0.01-0.72),P =0.03],while the incidence of nausea [RR =1.80,95 ％ CI(0.70-4.64),P =0.22],vomiting [RR =3.94,95％ CI (0.45-34.38),P=0.22] and constipation [RR=0.82,95％ CI (0.49-1.37),P=0.45] were similar.The incidence of nausea and vomiting of lanthanum carbonate group were similar with placebo,with lower incidence of constipation [RR =0.19,95 ％ CI (0.06-0.59),P ＜ 0.01].Conclusions The efficacy of lanthanum carbonate in treating hyperphosphatemia is similar with calcium carbonate.The incidence of hypercalcinemia of lanthanum carbonate is lower than that of calcium carbonate,and the incidence of gastrointestinal adverse effect such as nausea,vomiting and constipation are similar with calcium carbonate.
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A PAGE IEF immunoassay was established to detect the ORM, Pi, AHSG and GC phenotypes slmultaneously in human bloodstains. The cumulative discriminating power and probability of paternity exclusion were 0. 9878 and 0. 6648 respectively. Human sera diluted 100 times and bloodstains kept at room temperature for 4 weeks could be typed for these four blood groups correctly. The phenotypes of ORM, AHSG and GC could be determined correctly in bloodstains kept at room temperature within 24 weeks. This provides a good approach for individual identification of human bloodstains.