Anaplastic thyroid carcinoma(ATC)is the most aggressive malignancy with poor prognosis.The pathogenesis of ATC is complex,and there is no effective treatment at present.In recent years,with the deep understanding of the genetic(such as BRAF V600E,TP53,TERT,PIK3CA mutations,etc.)and epigenetic(such as histone methylation,histone deacetylation,microRNA regulatory pathways,etc.)changes driving ATC,molecular targeted therapy has brought new hope to ATC patients.This article reviews the molecular mechanisms of ATC and the latest achievements in targeted therapy and other therapies.

Objective:To investigate the expression of HBB in anaplastic thyroid cancer(ATC)cells and its regulatory effect on proliferation,invasion,migration and apoptosis of ATC cells and its potential mechanism.Methods:The expression of HBB in thyroid cancer and paracancerous tissues was analyzed through TIMER database.The correlation between the expression of HBB and the overall survival time of thyroid cancer patients was analyzed through KM-plotter database.The expression of HBB mRNA in ATC cells was detected by RT-qPCR.The HBB knockout or overexpression plasmid was transfected into ATC cells.The expression of HBB protein was detected by Western blot.The proliferation activity was detected by CCK-8 assay.The migration and invasion ability was detected by Transwell assay.The apoptosis was detected by flow cytometry.The expression of β-catenin was detected by Western blot.Results:The expression of HBB was low in thyroid cancer,and the overall survival time of patients with high expression of HBB was high.The expression of HBB protein was down-regulated in ATC cells.Knockout of HBB increased the ability of proliferation,migration and invasion of ATC cells and the expression of β-catenin protein,and inhibited apoptosis.However,overexpression of HBB decreased the ability of proliferation,migration and invasion of ATC cells and the expression of β-catenin protein,and promoted apoptosis.Conclusions:High HBB expression is associated with higher overall survival in patients with thyroid cancer.It may inhibit the proliferation,migration and invasion of ATC cells and promote apoptosis through Wnt/β-catenin signal pathway.

Objective To explore the effects of the long non-coding RNA(lncRNA)NK2 homeobox 1-antisense RNA 1(NK2-1-AS1),which mediates the microRNA(miR)-96-5p/PR domain-containing protein 16(PRDM16)axis,on anaplastic thyroid cancer(ATC)cell proliferation,migration,and invasion in vitro and transplanted tumor growth in vivo.Methods The differentially expressed lncRNA NKX2-1-AS1 in ATC tissues and cells,its target miRNA miR-96-5p,and its downstream target gene PRDM16 were screened using a bioinformatics analysis.The dual-luciferase reporter assay validated the relationship between NKX2-1-AS1 and miR-96-5p as well as the connection between miR-96-5p and PRDM16.Western blotting was performed to detect the effect of miR-96-5p overexpression on PRDM16 in CAL-62 cells overexpressed with NKX2-1-AS1.Plate clone formation,scratch,and Transwell assays were used to detect the effects of PRDM16knockdown on the proliferation,migration,and invasion of CAL-62 cells overexpressing NKX2-1-AS1.CAL-62 cells were injected subcutaneously into nude mice and the effect was observed of PRDM16knockdown on the growth of transplanted tumors of CAL-62 cells overexpressing NKX2-1-AS1.Results The bioinformatics analysis revealed that the NK2-1-AS1/miR-96-5p/PRDM16 axis was involved in regulating ATC development.The dual-luciferase reporter assay demonstrated that NKX2-1-AS1 bound to miR-96-5p and miR-96-5p bound to PRDM16.NKX2-1-AS1 overexpression upregulated PRDM16 protein expression in CAL-62 cells,while miR-96-5p overexpression reversed this phenomenon.NKX2-1-AS1 overexpression inhibited CAL-62 cellular proliferation,migration,and invasion in vitro and transplanted tumor growth in vivo,while knocking down PRDM16 reversed these phenomena.Conclusion NK2-1-AS1 may compete with miR-96-5p as an endogenous RNA to bind to its downstream target gene,PRDM16,and upregulate its expression,thus inhibiting ATC cell proliferation,migration,and invasion in vitro and transplanted tumor growth in vivo.

Objective To explore the effect of transcription factor E2F7 on the proliferation,migration,invasion,and tumor growth of anaplastic thyroid cancer(ATC)cells in vitro and to elucidate the underlying mechanisms.Methods Lentivirus transfection was used for a stable E2F7 knockdown in CAL-62 cells,and real-time PCR was used to detect E2F7 expression in these cells to verify the trans-fection efficiency.CAL-62 cells were divided into sh-NC and sh-E2F7 groups,and cell proliferation was measured using the CCK-8 assay,whereas cell migration and invasion abilities were measured using the Transwell assay.CAL-62 cells were subcutaneously injected into nude mice to observe tumor growth.The EPD website predicted an E2F7 binding site on the CXCL5 promoter,and the dual-lucif-erase reporter gene assay measured the effect of E2F7 knockdown on the luciferase activity of the CXCL5 promoter.The impact of E2F7 knockdown on CXCL5 levels in CAL-62 cells was assessed through real-time PCR and ELISA.Further,CAL-62 cells were divided into sh-E2F7+vector and sh-E2F7+CXCL5 groups to study the effects of CXCL5 overexpression on cell proliferation,migration,invasion,and the CXCR2/ERK signaling pathway following E2F7 knockdown.Results E2F7 knockdown inhibited CAL-62 cell proliferation,migra-tion,and invasion in vitro and tumor growth in vivo.The CXCL5 promoter has an E2F7 binding site,and E2F7 knockdown reduced the luciferase activity of the CXCL5 promoter.CXCL5 overexpression reversed the inhibitory effect of E2F7 knockdown on cell proliferation,migration,invasion,and the CXCR2/ERK signaling pathway in CAL-62 cells.Conclusion E2F7 promotes ATC cell proliferation,migra-tion,invasion,and tumor growth in vitro by activating the CXCL5/CXCR2/ERK signaling pathway mediated by CXCL5 transcription.

OBJECTIVE To investigate the modulating effect of neotropics on form deprivation myopia(FDM)in guinea pigs.METHODS Tricolour guinea pigs were randomly divided into normal control group,FDM model group,FDM+saline group,FDM+atropine group,and FDM+neotropine group,with eight animals in each group.Except for the normal control group,the right eyes of the guinea pigs were covered for 14 d to establish a guinea pig FDM model.The drug administration groups were injected with 10 μL of saline,1%atropine,or 1%neotropine into the vitreous cavity once every other day.The changes in the refractive error and axial length of both eyes were recorded for 1 d before the intervention and for 14 d after the intervention.Then,the eyeballs of guinea pigs were taken from the right eyes.HE staining was used to evaluate the histopathological structure of the sclera while sirius red staining was used to detect the collagen protein content in the sclera.RT-qPCR was used to detect the mRNA expressions of transforming growth factor-β1(TGF-β1),matrix metalloproteinase(MMP-2)and tissue inhibitor of metalloproteinase(TIMP-2)in guinea pigs'sclera.The protein expression levels of collagen type Ⅰ(Col-Ⅰ)and TGF-β1 in guinea pig sclera were detected by Western blotting while those of MMP-2,TIMP-2 and Ki-67 were detected by immunohistochemical staining.RESULTS Compared with the nor-mal control group,eyes of guinea pig in the FDM model group showed a significantly lower refractive error(P<0.01),significant elongation of the ocular axis(P<0.01),scattered distribution of scleral fibre bundles,sparse collagen cells,reduced scleral thickness(P<0.01),and a significantly lower collagen protein content(P<0.01).The mRNA and protein expressions of TIMP-2 and TGF-β1 were lower(P<0.05,P<0.01),and MMP-2 was higher(P<0.01)in scleral tissue.The protein expression level of Col-Ⅰwas lower(P<0.05)while that of Ki-67 was elevated(P<0.01)in scleral tissue.Compared with the FDM model group,there were no significant changes in any of the indexes in the FDM+saline group.The refractive error of the right eyes of guinea pigs in the FDM+neotropium group and the FDM+atropium group were significantly higher(P<0.05),the length of the ocular axis was significantly shorter(P<0.05),the collagen fibres were arranged more tightly,the fibre bundles were distributed more orderly,the distribution of the collagen cells was more uniform,and the thickness of the sclera was significantly increased(P<0.01).Collagen protein contents were significantly higher(P<0.05,P<0.01),the mRNA and protein expressions of TIMP-2 and TGF-β1 were significantly higher(P<0.01),MMP-2 mRNA and protein expressions were significantly lower(P<0.05,P<0.01).The protein expression level of Col-Ⅰwas higher(P<0.05,P<0.01),and that of Ki-67 was lower(P<0.05,P<0.01)in scleral tissue.CONCLU-SION The muscarinic antagonist neotropine inhibits the development of myopia in guinea pigs in the FDM model by reversing both the down-regulation of TGF-β1 and the up-regulation of MMP-2 in scleral tissues and inhibiting the remodeling of the scleral extracellular matrix.

Objective:To summarize the surgical experience of carotid body tumor (CBT)and analyze the risk factors.Methods:The clinical and follow-up data of 133 patients with carotid body tumor undergoing surgery at the First Medical Center of PLA General Hospital from Nov 2005 to Apr 2019 were retrospectively analyzed.Results:All of 142 tumors were successfully resected. No patients died perioperatively. Thirty-three (23.2%) cases underwent simple tumor resection, 82 (57.8%) cases underuent tumor resection combined with external carotid artery ligation, 13 (9.2%) cases did internal carotid artery reconstruction, 10 (7.0%) cases had total or external carotid artery repairment, and 4 (2.8%) cases underwent total or internal carotid artery ligation. There were 53 complications, including 43 cases of cranial nerve injury, with an average operating time of 161min (60-500 min), an average blood loss of 308 ml (20-3 000 ml). The follow-up time ranged from 1 to 162 months. No death occurred during the follow-up period.Conclusions:Tumor size and Shamblin typing are surgical risk factors. Most of ShamblinⅠtype tumor can do simple resection, but type Ⅱ and Ⅲ often need to ligate the external carotid artery. Use of great saphenous vein has a favorable long-term patency rate.

Objective:To summarize the midterm to long-term outcomes and experiences of endovascular treatment (ET) of spontaneous isolated superior mesenteric artery dissection (SISMAD).Methods:The clinical data of 31 SISMAD patients from Jan 2011 to Dec 2019 treated with ET was retrospectively analyzed.Results:Successful ET was achieved in 29 patients with a technical success rate of 93.5%. A total of 36 self-expandable bare stents were planted in 28 patients and plain old balloon angioplastry (POBA) was performed in 1 patient. Abdominal pain disappeared within 24 hours in 89.3% of the patients after stenting. The rate of perioperative complication was 3.2%. There was no SMA dissection rupture bleeding, nor perioperative death occurred. The mean follow-up time was 53.5 (range, 6 to 110) months. There was no dissecting aneurysm formation, no SMA rupture and bleeding, and no stent rupture during the follow-up. The post ET 1-year, 3-year, and 5-year free from reintervention rate were 100%, 100%, and 91.7%, respectively.Conclusions:ET for SISMAD is safe and effective with satisfactory perioperative and midterm to long-term outcomes.

Objective To investigate the safety and mid-term efficacy of percutaneous endovascular angioplasty(PTA) and stent implantation for transplantation renal arterial stenosis (TRAS).Methods Retrospective analysis was performed on 18 patients with TRAS admitted to of department vascular surgery,PLA General Hospital from Jan 2011 to Dec 2018.Results PTA and stent implantation were performed in all 18 patients via ipsilateral or contralateral femoral artery including 4 cases of PTA alone,8 cases of PTA plus stent,6 cases of stent implanted directly.Three of the 18 patients underwent ipsilateral femoral artery catheterization and 15 underwent contralaterally.A total of 14 stents were implanted,all of were balloon expanding stents,of which 2 were drug-coated stents,and the technical success rate was 100％.The average dosage of contrast agent was 64 ml,the stenosis rate of renal artery before interventional treatment was 50％-99％,and that after interventional treatment reduced to 10％-30％.The systolic blood pressure decreased from (157.2 ± 43.0) mmHg preoperatively to (129.8 ± 8.6) mmHg postoperatively.The SCr level decreased from (258.8 ± 214.7) μ mol/L to (176.3 ± 101.1) μmol/L.Preoperative urea nitrogen decreased from (15.7 ± 1.6) mmol/L to (10.6 ± 1.1) mmol/L postoperatively (P ＜ 0.05).Mean postoperative follow-up time was 42.4 months (3-93 months).17 cases were cured,1 case was ineffective,1 case suffered restenosis after 30 days,and was given remedy PTA plus stenting.Conclusions TRAS is a vascular factor leading to grafted renal failure,the endovascular treatment of TRAS is safe,effective and has good mid-term result.

Objective: To evaluate the safety and efficacy of the drug coated balloon(DCB) for complex TASC C/D superficial femora-popliteal artery diseases. Methods: Patency, target lesion revascularization (TLR) rate, clinical improvement and safety endpoints of femora-popliteal lesions in 68 patients from PLA General Hospital treated with DCB were retrospectively analyzed from June 2016 to June 2018. The mean age of the patients were (72.7±13.2) years old. Rutherford categories were from 2 to 5, and ABI baseline were 0.56±0.22. Results: There were 76 limbs treated by DCB in total in this study. Mean lesion length was (26.7±15.3) cm. 73.6% of lesions were totally occluded, 26.4% were of stenosis and 61.8% were highly calcified. Stent implantation was performed in 36.8% cases. Kaplan Meier estimates of primary patency were 74.2%±7.6% and 67.7%±6.4% at 1 and 2 years, respectively, whereas freedom from TLR was 81.4%±5.1% and 73.6%±5.4%. ABI were 0.83±0.16 at 1 year, and 0.79±0.24 at 2 years. Major amputation rate was 2.9% and mortality rate was 2.9% and 4.4% at 1 year and 2 years respectively. Diabetes, highly calcification, renal insufficiency and re-stenotic lesions were identified as predictors of restenosis. Conclusions DCB are safe and effective in delaying restenosis in complex TASC C/D superficial femora-popliteal artery disease as found by midterm follow-up.

Objective? To develop a nurse-patient communication process for patient with cancer in China based on the American CICARE communication model and to provide standardized and processed guidance for communication between clinical nurses and cancer patients. Methods? Totally 5 clinical nursing experts from a Class Ⅲ Grade A hospital in Beijing were selected by purposive sampling and interviewed using focus group discussion between November and December 2018. Results? The nurse-patient communication process was developed based on the CICARE communication model after two rounds of focus group discussions, whose six steps were polite connection, complete introduction, professional explanation, careful asking, patient response and proper exit, which included role adaptation of nurses, admission evaluation, coordination during hospitalization, case management, care and health education. Conclusions? A nurse-patient communication process for cancer patients in China is developed using nurse-patient communication models from other countries and clinical nursing practice for reference, which provides a reference for nurse-patients communication and lays a foundation for carrying out the optimal nursing service demo projects and refined management.