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Thyroid cancer is the most common malignant tumor of the endocrine system, and the incidence is increasing year by year, which seriously threatens people's health. Autophagy is a programmed mode of death that can be used as a potential target for anti-tumor therapy and plays an important regulatory role. Leucine-rich repeat kinase 2 (LRRK2) is a protein kinase encoded by PARK8 gene. The recent studies have confirmed that autophagy is closely related to thyroid cancer. This paper analyzes the possible regulatory mechanism of LRRK2 affecting thyroid cancer through autophagy, providing new ideas for basic research and clinical diagnosis and treatment of thyroid cancer.
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Objective To summarize our experience with surgical management of renal neoplasm involving inferoir veno cava.Methods We review the data of 115 patients,including 74 male patients and 41 female patients,with renal neoplasm involving venous system between March 1993 and December 2015.The mean age was 52 years old,ranging 22 to 77 years old.The tumor was found in right side in 77 cases and left side in 38 cases.There were 15 patients (13.0％) with renal vein thrombus,38 (33.1％) with infrahepatic thrombus,29 (25.2％) with low retrohepatic thrombus,20 (17.4％) with high retrohepatic thrombus,and 13 (11.3％) with supradiaphragmatic thrombus.The mean age was 52 years old,ranging 22 to 77 years old.The tumor was found in right side in 77 cases and left side in 38 cases.All patients accepted the radical nephrectomy.Primary outcomes were overall survival (OS),and cancer special survival (CSS) in patients with renal cell carcinoma (RCC) estimated by Kaplan-Meier method.Secondary outcome included operative and oncological features,past-operative complications and hospital mortality.Cox proportional hazard model was used to univariate and multivariate analysis for risk factor impacting on OS of RCC patients.Results Complete resections of renal neoplasm with tumor thrombus were achieved in 113 patients (98.3％),2 patients died intraoperatively due to the dropping of thrombus.Postoperative complication rate was 16.8％.Hospital mortality was 2.6％.Mean follow-up interval was 48 months.OS rates at 5-,and 10-year in RCC patients were 66.5％,and 61.8％,respectively.Metastasis was an independent risk factor affecting on OS (P =0.000).However,the level of thrombus was not an risk factor affecting the prognosis.Conclusions Radical resection of renal tumor and caval thrombus is an effective treatment for prolonging survival in patients with RCC extending into venous system.Retrohepatic caval tumor thrombus below or above the main hepatic vein should be dichotomized and managed respectively with diverse techniques.Metastatic rather than the level of thrombus was a risk factor impacting on RCC patient survival.
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Objective Using silkworm expression system to express human serum paraoxonase 1 (PON1) fusion protein with protein transduction domain P11 and to study its biological activity of fighting aginst the toxicity of dichlorvos. Methods P11-PON1 fusion gene was constructed in cloning sites of silkworm pFastBac 5B vector, the vector and was transformed to silkworm DH10BmBac competent cells. Virus particles and 5 instar silkworm was infected 96 hours after infection, parasites were collected and lyophilized crushed and preserved at-80℃. The protien was dissolved, sonicated and centrifuged before used. Supernatants were harvested. The fusion protein P11-PON1 proportion of the total protein was analyzed with SDS-PAGE electrophoresis and protein content was calculated. Mouse and zebrafish models were used to evaluate P11-PON1 fusion protein bioactivity. Each mouse was treated with 1 mg P11-PON1 fusion protein via intragastric or rectal administration. 0 and 3 hours after administration, 20 mg/kg dichlorvos were injected intraperitoneally. The status of intoxication was observed and the survival rate was scored. P11-PON1 fusion protein with concentrations of 1, 2.5, 5, 10, 20 mg/L was dissolved in zebrafish breeding water respectively. 0 and 3 hours after exposing dichlorvos were added with a final concentration of 50 mg/L. Observe their behavioral change.The survival rate of zebrafish was recorded. Results The content of P11-PON1 fusion protein was 8%of silkworm total protein. In mice experiments, P11-PON1 fusion protein by intragastric adminstration did not increase the survival of mouse. By intraperitoneal injection with dichlorvos 0h after rectal adminstration with protein,the survival rate of mouse did not significantly increase. In contrast, the mouse intraperitoneally injected with dichlorvos 3h after adminstration with protein, the survival rate increased extremely significantly (P < 0.01). In zebrafish experiments, the zebrafish exposed to dichlorvos 0 h after adminstration with protein, the survival rate was not significantly improved, while exposed to dichlorvos 3h after admindtration, the survival rate significantly increased. The survival rate of 20, 10, 5 mg/L group were 62.5%, 62.5%and 50%respectively at 24 h time point, compared to the control group. The survival rate increased extremely significantly (P < 0.01). 2.5 mg/L group was 41.7%, with the survival rate increasing significantly (P < 0.05). However, the survival rate of 1 mg/L group was 16.7%, compared to the control group. The increase had no sistatistical significance. Conclusion The PTD-containing PON1 fusion protein can be expressed in silkworm. Pretreatment with the fusion protein in mice and zebrafish decreased the toxicity of dichlorvos.
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OBJECTIVE To investigate the develop mental toxicity of muscone to embryos. METHODS With zebrafish embryos as a model,The 3 h post fertilization (hpf)embryos were exposed to muscone at 5,10,20,40,80 and 160 μmol·L -1 culture solutions for 96 h and inspected daily with mi-croscopy for larval morphology.The drug solution was replaced every 24 h.Spontaneous move ments were checked at 24 hpf.Heart rate at 48 hpf,hatching rate,e mbryo deformity rate and mortality rate were evaluated.The expression of sepn1 was determined with real-ti me quantitative PCR technique at 96 hpf.RESULTS The 24 hpf spontaneous move ments showed no significant difference.At 48 hpf, spine curvature,pericardial ede ma,yolk sac ede ma,and abnormal swi mming were observed.In addition, the 48 hpf heart beats(10 s)was decreased fro m 26.5 ±1 .0 to 18.0 ±1 .9(P <0.01 ).At 48 hpf , hatching rate of 5 ~40 μmol·L -1 decreased(P <0.05),while of 160 μmol·L -1 increased (P <0.05) co mpared with muscone 0 μmol·L -1 .Muscone had little effect on hatching rate at other ti me points;Mal-formation rate and mortality rate at higher concentrations were up to 100%.The sepn1 gene expression at 96 hpf in the exposure groups decreased co mpared with that of control group(P <0.01 ).CONCLU-SION Muscone had toxic effects on the develop ment of zebrafish embryos,including spine curvature, abnormal swi mming,and pericardial ede ma.These effects may be related to the inhibition of sepn1 gene expression by muscone.
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The mechanism of Tongmai Oral Liquid (TOL) for chronic nephritis rat model with Qi-deficiency and blood-stasis syndrome was studied.The model was established by adding Qi-deficiency and blood-stasis syndrome to the chronic nephritis rats. The experimental rats were randomly allocated to 5 groups: Group A (treated with high dosage of TOL), Group B (treated with low dosage of TOL), Group C (treated with Jinshuibao), Group D (model control group) and Group E (normal control group). After 4 weeks of treatment, general health state, biochemical indexes including T lymphocyte subgroup and blood rheology, and pathological damage of kidney tissue were much improved in Group A than Group B and Group C. It is indicated that TOL can improve the renal function and delay the occurrence of glomerular arteriosclerosis in rats by reinforcing Qi, activating blood flow, regulating immune function, lessening the hypercoagulative state and reducing renal damage.