Objective At the level of human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)and neonatal rat cardiomyocytes(NRVMs),investigate the role of serum glucocorticoid regulated kinase 1(SGK1)in the myocardial injury caused by sunitinib and the potential protective effect of berberine.Methods Enzyme-linked immunosorbent assay was used to detect the effect of sunitinib and incubation with berberine on the level of NT-proBNP and cTn-I in hiPSC-CMs.The effect of sunitinib and incubation with berberine on the activity of SGK1 in hiPSC-CMs was quantitatively tested using kinase activity photometry.Western blot was used to detect the expression of SGK1 in NRVMs.And the above indicators were detected again after SGK1 blockade using SGK1 blocker.Results Sunitinib and SGK1 inhibitor significantly increased the NT-proBNP and cTn-I level of hiPSC-CMs(P<0.01),and incubation with berberine activated SGK1 could significantly protect hiPSC-CMs from the increase in NT-proBNP level caused by sunitinib(P<0.01),while the SGK1 inhibitor resisted the protective effect of berberine(P<0.01).Sunitinib and SGK1 inhibitor significantly decreased the activity of SGK1 in hiPSC-CMs(P<0.01),and incubation with berberine activated SGK1,which significantly protected hiPSC-CMs from the inhibition of SGK1 activity caused by sunitinib(P<0.01).Sunitinib and SGK1 inhibitors significantly reduced SGK1 protein expression in NRVMs(P<0.01),and incubating berberine to activate SGK1 significantly protected SGK1 protein expression decrease induced by sunitinib(P<0.01).Conclusions Sunitinib inhibits the activity of SGK1,leading to myocardial injury,while berberine activates SGK1 and has protective effects.

Objective To explore the reasons for the activation of the RNA-binding protein ZC3H15 in non-small cell lung canc-er and its biological functions in the tumorigenesis of non-small cell lung cancer.Methods Based on the whole genome sequencing data of The Cancer Genome Atlas(TCGA)database,the relationship between ZC3H15 copy number variation and its expression was analyzed,and the differential expression of ZC3H15 between normal and non-small cell lung cancer groups,its variation across different TNM sta-ges,and its prognostic analysis were investigated.A549 cells and PC9 cells were divided into si-NC group and si-c-Myc group,re-spectively.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and chromatin immunoprecipitation were used to explore the regulatory relationship between the transcription factor c-Myc and ZC3H15.A549 cells and PC9 cells were divided into si-NC group,si-ZC3H15 1# group,si-ZC3H15 2# group,Vector group,pcDNA-ZC3H15group.RT-qPCR was used to detect the ex-pression of ZC3H15,MTT assay was used to detect cell viability,colony formation assay was used to examine cell proliferation capacity,and Transwell assay was used to measure cell migration ability.The A549 cells were stably transfected with sh-Ctrl and sh-ZC3H15,and the nude mouse xenograft model was used to detect the impact of ZC3H15 on the proliferation ability of non-small cell lung cancer cells in vivo.Results TCGA non-small cell lung cancer data analysis showed that the expression level of ZC3H15 in the copy-number-amplified group was higher than that in the copy-number-deleted group(P＜0.05).ZC3H15 copy number was positively correlated with expression level(P＜0.05).In both paired and unpaired non-small cell lung cancer groups,the expression level of ZC3H15 was up-regulated compared to the normal group(P＜0.05).The expression level of ZC3H15 was higher in stage Ⅲ/Ⅳ group than that in stage Ⅰ/Ⅱ group(P＜0.05).The low-expression ZC3H15group had a higher survival rate than the high-expression group(P＜0.05).Compared to the si-NC group,the expression level of ZC3H15 and Input reference percentage after c-Myc antibody treatment in the si-c-Myc group were both decreased(P＜0.05).The results of RT-qPCR showed that in A549 cells and PC9 cells,the expression level of ZC3H15 in the si-ZC3H15 1# and si-ZC3H15 2# groups were lower than those in the si-NC group(P＜0.05),while the expression level of ZC3H15 in the pcDNA-ZC3H15group was higher than that in the Vector group(P＜0.05).Further cell func-tion studies found that the proliferation and migration capacity of non-small cell lung cancer cells with ZC3H15 knockdown were decreased(P＜0.05),and the overexpression of ZC3H15 could enhance the proliferation and migration capacity of non-small cell lung cancer cells(P＜0.05).At the in vivo level,subcutaneous tumor-bearing experiments in nude mice showed that ZC3H15 knockdown could significant-ly reduced the tumor growth rate(P＜0.05).Conclusion Copy number amplification and c-Myc transcriptional activation were important reasons for ZC3H15 activation in non-small cell lung cancer.ZC3H15 is a key functional molecule to promote the tumorigenesis of non-small cell lung cancer,and can provide some theoretical basis for clinical diagnosis and treatment of non-small cell lung cancer.

Objective At the level of human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)and neonatal rat cardiomyocytes(NRVMs),investigate the role of serum glucocorticoid regulated kinase 1(SGK1)in the myocardial injury caused by sunitinib and the potential protective effect of berberine.Methods Enzyme-linked immunosorbent assay was used to detect the effect of sunitinib and incubation with berberine on the level of NT-proBNP and cTn-I in hiPSC-CMs.The effect of sunitinib and incubation with berberine on the activity of SGK1 in hiPSC-CMs was quantitatively tested using kinase activity photometry.Western blot was used to detect the expression of SGK1 in NRVMs.And the above indicators were detected again after SGK1 blockade using SGK1 blocker.Results Sunitinib and SGK1 inhibitor significantly increased the NT-proBNP and cTn-I level of hiPSC-CMs(P<0.01),and incubation with berberine activated SGK1 could significantly protect hiPSC-CMs from the increase in NT-proBNP level caused by sunitinib(P<0.01),while the SGK1 inhibitor resisted the protective effect of berberine(P<0.01).Sunitinib and SGK1 inhibitor significantly decreased the activity of SGK1 in hiPSC-CMs(P<0.01),and incubation with berberine activated SGK1,which significantly protected hiPSC-CMs from the inhibition of SGK1 activity caused by sunitinib(P<0.01).Sunitinib and SGK1 inhibitors significantly reduced SGK1 protein expression in NRVMs(P<0.01),and incubating berberine to activate SGK1 significantly protected SGK1 protein expression decrease induced by sunitinib(P<0.01).Conclusions Sunitinib inhibits the activity of SGK1,leading to myocardial injury,while berberine activates SGK1 and has protective effects.

Objective To explore the reasons for the activation of the RNA-binding protein ZC3H15 in non-small cell lung canc-er and its biological functions in the tumorigenesis of non-small cell lung cancer.Methods Based on the whole genome sequencing data of The Cancer Genome Atlas(TCGA)database,the relationship between ZC3H15 copy number variation and its expression was analyzed,and the differential expression of ZC3H15 between normal and non-small cell lung cancer groups,its variation across different TNM sta-ges,and its prognostic analysis were investigated.A549 cells and PC9 cells were divided into si-NC group and si-c-Myc group,re-spectively.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and chromatin immunoprecipitation were used to explore the regulatory relationship between the transcription factor c-Myc and ZC3H15.A549 cells and PC9 cells were divided into si-NC group,si-ZC3H15 1# group,si-ZC3H15 2# group,Vector group,pcDNA-ZC3H15group.RT-qPCR was used to detect the ex-pression of ZC3H15,MTT assay was used to detect cell viability,colony formation assay was used to examine cell proliferation capacity,and Transwell assay was used to measure cell migration ability.The A549 cells were stably transfected with sh-Ctrl and sh-ZC3H15,and the nude mouse xenograft model was used to detect the impact of ZC3H15 on the proliferation ability of non-small cell lung cancer cells in vivo.Results TCGA non-small cell lung cancer data analysis showed that the expression level of ZC3H15 in the copy-number-amplified group was higher than that in the copy-number-deleted group(P＜0.05).ZC3H15 copy number was positively correlated with expression level(P＜0.05).In both paired and unpaired non-small cell lung cancer groups,the expression level of ZC3H15 was up-regulated compared to the normal group(P＜0.05).The expression level of ZC3H15 was higher in stage Ⅲ/Ⅳ group than that in stage Ⅰ/Ⅱ group(P＜0.05).The low-expression ZC3H15group had a higher survival rate than the high-expression group(P＜0.05).Compared to the si-NC group,the expression level of ZC3H15 and Input reference percentage after c-Myc antibody treatment in the si-c-Myc group were both decreased(P＜0.05).The results of RT-qPCR showed that in A549 cells and PC9 cells,the expression level of ZC3H15 in the si-ZC3H15 1# and si-ZC3H15 2# groups were lower than those in the si-NC group(P＜0.05),while the expression level of ZC3H15 in the pcDNA-ZC3H15group was higher than that in the Vector group(P＜0.05).Further cell func-tion studies found that the proliferation and migration capacity of non-small cell lung cancer cells with ZC3H15 knockdown were decreased(P＜0.05),and the overexpression of ZC3H15 could enhance the proliferation and migration capacity of non-small cell lung cancer cells(P＜0.05).At the in vivo level,subcutaneous tumor-bearing experiments in nude mice showed that ZC3H15 knockdown could significant-ly reduced the tumor growth rate(P＜0.05).Conclusion Copy number amplification and c-Myc transcriptional activation were important reasons for ZC3H15 activation in non-small cell lung cancer.ZC3H15 is a key functional molecule to promote the tumorigenesis of non-small cell lung cancer,and can provide some theoretical basis for clinical diagnosis and treatment of non-small cell lung cancer.

Objective:To investigate the clinical features, diagnosis, treatment and prognostic factors of intracranial ependymoma in children.Methods:The clinical data of 32 children with intracranial ependymoma treated in the Department of Neurosurgery, Beijing Children′s Hospital of Capital Medical University from January 2012 to December 2020 were retrospectively analyzed.There were 23 males and 9 females.The median age of diagnosis was 4.5 years old (0.7-10.0 years old). Twelve cases (37.5%) were less than 3 years old and 20 cases (62.5%) were more than 3 years old.Tumors were supratentorial in 14 cases and infratentorial in 18 cases.All patients underwent tumor resection.Eighteen cases received postoperative radiotherapy, and 20 cases received chemotherapy.Four cases took neither radiotherapy nor chemotherapy. Kaplan- Meier method was used to establish the survival curve the intracranial ependymoma patients.Whether the difference of a single variable was significant was examined by the Log- rank test. Results:Of the 32 patients, 30 cases underwent gross total resection and 2 underwent subtotal resection.The mean follow-up time was 24 months (1-62 months). By the time of the last follow-up, 26 cases survived and 6 cases died.The 1-year and 3-year survival rates were 88% and 78%, respectively.Univariate analysis showed that the tumor location ( OR=1.5, 95% CI: 1.082-2.079, P=0.040) greatly affected the overall survival time in children with intracranial ependymoma, and chemotherapy ( OR=0.5, 95% CI: 0.125-1.999, P=0.034) had significant impact on the overall survival time of patients younger than 3 years old. Conclusions:Intracranial ependymoma is more prone to occur in the infratentorial region than the supratentorial region.The tumor location is an important factor affecting the survival of children with ependymoma.For children younger than 3 years old, postoperative chemotherapy can well improve the prognosis, but cannot change the progress of the disease development.

Objective: Exploring the feasibility of the 2014 European Society of Cardiology(ESC)guideline′s risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD) in Chinese patients. Methods: The study population consisted of a consecutive cohort of 172 Chinese patients with HCM without prior sudden cardiac death (SCD) event who were in patients in Nanjing Drum Tower Hospital from December 2010 to October 2015.The endpoint event was a composite of SCD and appropriate implantable cardioverter-defibrillator (ICD) therapy.Clinical data were collected to calculate the 5-year SCD risk using the HCM Risk-SCD formula and to observe the actual risk during the follow-up.Receiver operating characteristic curves (ROC) and the area under curve (AUC) were calculated for the HCM Risk-SCD and risk stratification methods of the 2011 American Heart Association (AHA) guideline. Results: During follow-up of (2.69±1.36) years, five patients achieved the endpoint event.The predicated rate of SCD event using HCM Risk-SCD was (2.36±1.73)%, (1.93±0.78)%, (5.18±0.65)%, (8.77±2.38)% for all patients, low-risk group, medium-risk group and high-risk group respectively.However, the actual rate of SCD event was 2.91%, 1.27%, 25.00% and 14.29%, respectively.The AUC of 2014 ESC guideline and 2011 AHA guidelinewas 0.93(95%CI 0.85-1.00) vs. 0.87(95%CI 0.75-0.98). Conclusion The predicated rate of SCD event calculated by HCM Risk-SCD is lower than actual rate of SCD, but the prediction efficiency and indication for ICD implantation of HCM Risk-SCD are better than that of 2011 AHA guideline.

Objective To analyze the value of plane QRS-T angle on prediction of malignant ventricular arrhythmia (MVA) occurred after emergency percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods The clinical data of 418 patients with STEMI who underwent PCI within 12 h of symptom onset were retrospectively analyzed, and the patients were divided into plane QRS-T angle ≤ 90° group (324 cases) and plane QRS-T angle>90° group (94 cases) according to the plane QRS-T angle after PCI. The clinical data were compared between 2 groups. Results Compared with patients in plane QRS-T angle ≤ 90° group, patients in plane QRS-T angle > 90° group was older: (67.4 ± 11.8) years vs. (63.6 ± 12.0) years, QTc interval was longer: (438.60 ± 34.97) ms vs. (425.24 ± 25.49) ms, rate of left ventricular ejection fraction (LVEF) <45% was higher: 57.4% (54/94) vs. 35.8% (116/324), rate of using of beta-blockers was less: 74.5% (70/94) vs. 84.9% (275/324), but the incidences of hypertension and MVA were higher:79.8%(75/94) vs. 64.5%(209/324) and 10.6%(10/94) vs. 1.2%(4/324), and there were statistical differences (P<0.01 or<0.05). Logistic regression analysis showed that plane QRS-T angle >90° was an independent risk factor of MVA after PCI in STEMI patients (OR = 9.640, P =0.001), and using of beta-blockers was a protective factor (OR = 0.266, P = 0.028). Conclusions Plane QRS-T angle>90° is an independent risk factor of MVA after PCI in STEMI patients, while the use of beta-blockers is a protective factor. Paients with STEMI after PCI should be alert to the occurrence of MVA in the condition of plane QRS-T angle>90° and not taking beta-blockers.

Objective To retrospectively assess the diagnostic value of nuchal translucency (NT) thickness and facial profile ultrasonic markers [including frontomaxillary facial (FMF) angle,and the ratio of prenasal thickness to nasal bone length (PT/NBL)] for trisomy 21 syndrome in first-trimester fetuses.Methods Ultrasonograhic images of 35 fetuses with trisomy 21 syndrome and 70 gestational age matched normal fetuses were analyzed in first-trimester.NT,FMF angle and the PT/NBL ratio were measured retrospectively in stored images from digital database between January 2012 and December 2015.The diagnostic value of NT,FMF angle and PT/NBL ratio were compared with different combinations.Results (1) The mean NT was significantly higher in the trisomy 21 group than that in controls (t =7.401,P =0.00).The NT above 2.5mm was observed in 20 trisomy 21 fetuses (57.1％) and in 3 normal fetuses (4.3％).(2) The mean FMF angle was significantly higher in the trisomy 21 group than that in controls (t =-5.283,P =0.00).The FMF angle above the 95th percentile (93.6°) was observed in 13 trisomy 21 fetuses (37.1％) and in 1 normal fetus (1.4％).(3) The mean PT/NBL ratio was significantly higher in the trisomy 21 group than that in controls (t =-7.826,P =0.00).The PT/NBL ratio above the 95th percentile (0.93) was observed in 19 trisomy 21 fetuses (54.3％) and in 4 normal fetuses (5.7％).(4) The sensitivity and Youden index for trisomy 21 increased gradually,which were 57.1 ％ and 0.528 by using NT,and 74.3％ and 0.686 by using NT and FMF angle,and 91.4％ and 0.828 by using NT,FMF angle and PT/NBL ratio.There were significant differences in the detection rates of trisomy 21 among the three strategies,while the diagnostic specificity of the three strategies were more than 90％.Conclusions The three parameters are significantly increased in trisomy 21 fetus in first-trimester.First,increased NT was most commonly detected,followed by increased PT/NBL ratio,and increased FMF angle again.Detection rates for trisomy 21 fetuses in first-trimester by ultrasound screening can be significantly improved if combination of all three parameters rather than just one parameter are performed.

Objective To explore the correlation of the TIAM2 functional gene mutations with the bleeding events in patients with coronary heart disease who undergone PCI and postoperative taken anti-platelet drug clopi-dogrel. Methods One hundred and twenty Chinese Han patients who had undergone PCI and postoperative taken anti-platelet drug clopidogrel were orderly enrolled from Guangdong General Hospital. Followed for 6 months after PCI, PCR sequencing was applied to test TIAM2 promoter region genotyping assay. Results After follow-up six months , 113 cases were remained lost of 7 cases , , including 19 cases with bleeding and 94 cases without bleed-ing; Bleeding risk in patients with diabetes mellitus (OR=3.115) or taking statins (OR=11.539), may be high, but there was no significant difference (P > 0.05); TIAM2 promoter region had three variants (c.3168+3116C>T, c.3168+3261A>G,c.3168+3596A>C), including wild-type, heterozygous, and homozygous. The probability of pa-tients with bleeding were 36.84%, 52.63%and 10.53%, and there is a certain chain of state , but the genotype was not significantly correlated with bleeding events of clopidogrel antiplatelet therapy (P>0.05). Conclusion Clopi-dogrel antiplatelet therapy bleeding events were not significantly correlated with TIAM2 functional gene mutation.

Objective To investigate the impact of migration inhibitory factor (MIF) over-expression on the epithelial to mesenchymal transition in human cervical cancer SiHa cells.Methods Recombinant plasmid pEGFP-N1-MIF was transfected into SiHa cells,and then of MIF mRNA relative quantitative expression was tested by RT-PCR.The mRNA and protein expression level of E-cadherin and vimentin were detected by RT-PCR and immunocytochemistry,respectively.Results RT-PCR results showed that MIF mRNA expression quantity in experimental group was higher than that in control group cells (F =2 950.278,P ＜ 0.01).In MIF-overexpressing SiHa cells,vimentin mRNA was increased and E-cadherin mRNA was decreased determined by RT-PCR (Fvalues were 2 135.048,1 893.563,P＜ 0.01).Immunocytochemistry results showed that vimentin expression quantity in experimental group cells were higher than that in control group cells,however,E-cadherin expression quantity was lower than that in control group cells (F values were 2 348.021,1 789.421,P ＜ 0.01).Conclusions The over-expression of MIF gene can significantly up-regulate the expression of vimentin,and down-regulate the expression of E-cadherin.Consequently,MIF over-expression induces epithelial to mesenchymal transition in human cervical cancer SiHa cells.