Objective:To explore the effects of hinokiol on the cell cyle and apoptosis of CNE1 nasopharyngeal carcinoma cells and the relevant molecular mechanism.Methods:The CNE1 cells were cultured in vitro and incubated with different concentrations of honokiol, and the cells were divided into blank control group, 10 μmol/L, 20 μmol/L and 40 μmol/L hinokiol treatment groups, and 10 μg/ml cisplatin group. Cell viability was determined by methylthiazolyldiphenyl- tetrazolium bromide (MTT) method, the cell cycle distribution was detected by flow cytometry, mitochondrial membrane potential was detected by mitochondrial membrane potential test kit, apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and the proteins expression of proliferating cell nuclear antigen (PCNA) and G 1/S specific cyclin D1 (cyclin D1) were detected by immunoblotting. RNA-Seq was conducted in the hinokiol-treated cells. The mRNA expression of yes-associated protein delta (YAP) was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The proteins expression of phosphor-YAP (p-YAP) and nuclear YAP were detected by immunoblotting, the nuclear distribution of YAP protein was detected by immunofluorescence in the cells with or without treated with the mammalian STE20-like kinase 1/2 (MST1/2) inhibitor (XMU-MP-1), hinokiol, and XMU-MP-1+hinokiol. Statistical analysis of the data was conducted using GraphPad Prism 8.0 software. Resluts Compared with the control group, the cell viablity of CNE1 cells, the levels of mitochondrial membrane potential, the proteins expression of PCNA and cyclin D1 in hinokiol treatment groups were markedly decreased (all P values<0.05), while the proportion of G 0/G 1 phase cells and the ratio of TUNEL-positive cells were significantly increased (both P values<0.05). Transcriptome analysis showed that differential genes were mainly enriched in Wnt signaling pathway, tumor necrosis factor pathway, and Hippo signaling pathway. The mRNA level of YAP and the protein expression of YAP in the nucleus were decreased and the level of p-YAP protein was increased in cells treated with hinokiol, which were significantly different from control group (all P values<0.05). Compared with the hinokiol group, XMU-MP-1+hinokiol groups showed the decrease of p-YAP protein expression (1.157±0.076 vs 0.479±0.038, t=37.120, P<0.05), the increase of YAP protein expression in the nucleus (0.143±0.012 vs 0.425±0.031, t=29.181, P<0.05), the reduced proportion of cells in G 0/G 1 phase [(72.494±3.309)% vs (58.747±2.865)%, t=17.265, P<0.05], and the decrease of apoptosis ratio [(53.158±3.376)% vs (29.621±2.713)%, t=28.584, P<0.05]. Conclusion:Hinokiol can arrest the cell cycle and induce the cell apoptosis of CNE1 cells via Hippo/YAP signaling pathway.

Objective To screen out the biomarkers linked to prognosis of breast invasive carcinoma based on the analysis of transcriptome data by random forest(RF),extreme gradient boosting(XGBoost),light gradient boosting machine(LightGBM),and categorical boosting(CatBoost).Methods We obtained the ex-pression data of breast invasive carcinoma from The Cancer Genome Atlas and employed DESeq2,t-test,and Cox univariate analysis to identify the differentially expressed protein-coding genes associated with survival prog-nosis in human breast invasive carcinoma samples.Furthermore,RF,XGBoost,LightGBM,and CatBoost mod-els were established to mine the protein-coding gene markers related to the prognosis of breast invasive cancer and the model performance was compared.The expression data of breast cancer from the Gene Expression Omnibus was used for validation.Results A total of 151 differentially expressed protein-coding genes related to survival prog-nosis were screened out.The machine learning model established with C3orf80,UGP2,and SPC25 demonstrated the best performance.Conclusions Three protein-coding genes(UGP2,C3orf80,and SPC25)were screened out to identify breast invasive carcinoma.This study provides a new direction for the treatment and diagnosis of breast invasive carcinoma.

Humans ; Carcinogenesis/genetics* ; Gene Expression Regulation, Neoplastic ; Genes, cdc ; Nasopharyngeal Carcinoma/genetics* ; Nasopharyngeal Neoplasms/genetics* ; RNA Helicases/metabolism*

Objective:To investigate the efficacy and safety of Treprostinil in the treatment of children with early decompensation after the Fontan procedure.Methods:A retrospectively analysis was performed on the clinical data of 16 children with early decompensation after the Fontan procedure treated with Treprostinil injection from December 2017 to June 2020 at Fuwai Central China Cardiovascular Hospital.A total of 16 patients were included, including 5 boys (31.2%) and 11 girls (68.8%). The age was (4.6 ±1.2) years, the weight was (16.0±2.1) kg.The changes of central venous pressure (CVP), heart rate (HR), systolic blood pressure (SBP), central venous oxygen saturation (ScvO 2), lactic acid (Lac), oxygenation index and B-type natriuretic peptide (BNP) were recorded at the infusion of Treprostinil and 3 hours, 24 hours, 48 hours and 72 hours after the infusion.The short-term efficacy of Treprostinil was observed[mortality, mechanical ventilation time, and length of intensive care unit (ICU) stay]; paired t-test was used to analyze the above indexes at different time points.The adverse reactions during the administration were also recorded. Results:Of the 16 children, the median mechanical ventilation time was 9 (5, 22) h, and the median ICU stay time was 2 (1, 12)days.After 72 hours of drug administration, CVP, Lac, BNP and HR decreased: CVP decreased from(16±5) mmHg (1 mmHg=0.133 kPa) to (11±2) mmHg ( P<0.001), Lac decreased from(6.8±3.2) mmol/L to (3.2±1.2) mmol/L ( P=0.002), BNP decreased from(980±223) ng/L to (250±120) ng/L( P<0.001), HR decreased from(150±20) times/min to (125±16) times/min( P=0.002); SBP, ScvO 2 and oxygenation index increased: SBP increased from(83±10) mmHg to (98±12) mmHg( P<0.001), ScvO 2 increased from 0.53±0.13 to 0.65±0.11 ( P=0.003), oxygenation index increased from (200±72) mmHg to (298±13) mmHg ( P<0.001), and the differences were statistically significant(all P< 0.05). One case died (6.3%), 2 cases (12.5%) had transient blood pressure drop and 1 case (6.3%) had nausea and vomiting.Besides, no other treatment-related complications were observed. Conclusions:As for children with early decompensation after the Fontan procedure, the intravenous application of Treprostinil can reduce pulmonary artery pressure rapidly, effectively improve circulatory status and oxygenation and ultimately improve the prognosis.

Objective:To evaluate the medium-term clinical and hemodynamic outcomes of percutaneous pulmonary valve implantation (PPVI) using a domestic Venus-P self-expanding valve in the treatment of severe pulmonary regurgitation after Tetralogy of Fallot (TOF).Methods:Retrospective study.From December 2017 to December 2020, 13 TOF patients with (17.8±4.7) years old and (50.2±12.3) kg underwent PPVI using the Venus-P self-expanding valve in the Department of Children′s Heart Center, Zhengzhou University People′s Hospital were recruited.The mean valve size was (31.9±3.1) mm.All patients received the transannular patch surgery and developed severe pulmonary regurgitation.After PPVI, 13 patients were followed up for at least 12 months.The operation-related complications, improvement of valve and heart function and the durability and reintervention of the Venus-P self-expanding valve were analyzed.The right ventricular end-diastolic volume index (RVEDVi) before and after operation was compared by the paired t-test, and the New York Heart Association (NYHA) class was compared by the paired Wilcoxon signed rank sum test. Results:PPVI was successfully performed in all 13 patients without death.At 6 months post-PPVI, cardiac magnetic resonance imaging findings showed that RVEDVi was significantly reduced[(145.7±9.6) mL/m 2vs.(100.2±12.2) mL/m 2, P<0.05], and the NYHA class was significantly improved ( P<0.05). One patient presented moderate pulmonary valve regurgitation at 12 months postoperatively.No vegetation was found on echocardiography, and blood culture was negative in this case.Six patients did not have postoperative pulmonary valve regurgitation, and the remaining presented mild or less pulmonary regurgitation.One patient had sudden ventricular tachycardia on the 6 th day postoperatively, which was converted to sinus rhythm after synchronous electrocardiography.Only one case underwent appendectomy 7 months after operation due to acute appendicitis, and the remaining did not require valve-related reintervention after implantation.During the follow-up for (22.8±8.0) months, no patients had perivalve leakage, stent migration and rupture.Complications like embolization and coronary artery compression were not reported. Conclusions:PPVI using the Venus-P self-expanding valve is safe and effective in patients with severe pulmonary valve regurgitation after TOF surgery, showing an acceptable medium-term follow-up outcome.Studies with a large sample size and long follow-up period are still needed to validate our findings.

Objective : To investigate the pathogenic factors and clinical manifestations of contact stomatitis, and to provide references for its clinical diagnosis and prevention. Methods: The data of 55 subjects with contact stomatitis were analyzed retrospectively, including age, gender, pathogenic factors, type of lesions and site of occurrence. Results: Among the 55 patients, contact stomatitis occurred at all ages, 19 were male, 36 were female, and the ratio of males to females was 1∶1.89. Among 55 patients, 78.18% (43/55) were caused by oral mucosal contact with dental materials: amalgam fillings accounted for 52.73% (29/55), metal crowns accounted for 9.09% (5/55), removable denture plastic bases accounted for 9.09% (5/55), resin fillings accounted for 5.45% (3/55), and alginate impression materials accounted for 1.82% (1/55); 21.82% (12/55) were caused by oral mucosal contact with food and daily necessities. The clinical manifestations of contact stomatitis include lichenoid reaction, erythema and erosion. The most common site of contact stomatitis was the cheek, followed by the tongue, and the lips, and the gingival and palatal areas were relatively rare. In the buccal mucosa, the incidence of lichenoid reaction was 55% (22/40), which was higher than that of erosion (20%) and erythema (25%), and the difference was statistically significant (P < 0.05). For tongue, lip, gingiva and palate, there was no significant difference in the incidence of the three lesion types（P > 0.05）. Conclusion Contact stomatitis occurred at all ages, and there are more female patients than males with contact stomatitis. Dental materials, especially metal and acrylic materials (such as the plastic base of removable dentures, resin fillings, adhesives, and self-setting plastics), are the main pathogenic factors. In buccal mucosa, the incidence of lichenoid reaction is higher.

Objective: To investigate the efficacy of Levosimendan in the treatment of postoperative low cadiac output syndrome (LCOS) in infants with congenital heart disease (CHD). Methods: Clinical data of patients with CHD developed postoperative LCOS in the Children Heart Center of Fuwai Central China Cardiovascular Hospital from January to December 2018 was collected.In patients that traditional vasoactive drugs failed to alleviate LCOS, the efficacy of continuous infusion of 0.1 μg/(kg·min) Levosimendan was observed.Besides, the mechanical ventilation time, ICU stay time, mortality, the changes of ejection fraction (EF) and central venous oxygen saturation (ScvO₂) at the infusion of Levosimendan and 48 h after infusion, as well as the changes of heart rate (HR), systolic blood pressure (SBP), vasoactive drugs score (VIS) and lactic acid at the infusion of Levosimendan and 3 h, 6 h, 12 h, 24 h and 48 h after infusion were recorded. Results: There were 29 cases, including 17 males (58.6%) and 12 females (41.4%), with median age of 2 (0.5, 40.0) months, median body mass of 4.7 (2.6, 13.5) kg, median mechanical ventilation time of 109.5 (42.5, 367.0) h, ICU stay time of 187.5 (83, 446) h, and 1 case died (3.4%). EF (48% vs.52%) and ScvO₂ (53% vs.58%) increased 48 h after infusion, and the differences were statistically significant (all P<0.01). HR level (173 times/min, 176 times/min, 175 times/min, 173 times/min, 170 times/min, 170 times/min) and lactic acid level (4.72 mmol/L, 4.65 mmol/L, 4.34 mmol/L, 3.79 mmol/L, 3.28 mmol/L, 2.74 mmol/L) gradually decreased after infusion, and the differences of both between the beginning of infusion and 48 h after infusion were statistically significant (P=0.029); SBP decreased and then increased (74 mmHg, 70 mmHg, 71 mmHg, 73 mmHg, 74 mmHg, 75 mmHg, 1 mmHg=0.133 kPa), and VIS increased and then decreased (26 scores, 27 scores, 27 scores, 26 scores, 25 scores, 25 scores) at different time points after infusion, however, the data of both between the beginning of infusion and 48 h after infusion had no significant differences (P=0.294, 0.151). Conclusions Levosimendan can increase EF, enhance myocardial contractility and systemic tissue perfusion, thus improving the prognosis, when Levosimendan was applied for the treatment of postoperative LCOS of infants with CHD.

Objective:To explore the risk factors of puncture- or catheter-related lower extremity venous thrombosis after surgery for congenital heart disease(CHD).Methods:A retrospective analysis was performed on 683 children with venipuncture or venous catheterization in the lower extremities who underwent surgery for CHD in Children′s Heart Center Intensive Care Unit, Henan Provincial People′s Hospital from January 2017 to December 2018, and there were 55 children suspected thrombosis, among whom, 26 cases of thrombosis confirmed by ultrasound were included in the thrombosis group, and 29 cases without thrombosis seen by ultrasound were assigned to the control group.A comparative analysis was carried out to see whether there were statistical differences in the possible risk factors between the 2 groups, and the risk factors of puncture- or catheter-related lower extremity venous thrombosis after operation of CHD.Results:The incidence of puncture- or catheter-related lower extremity venous thrombosis after surgery for CHD was 3.81% (26/683 cases). The differences between the thrombosis group and the control group in age (62 d vs.92 d), weight [(3.92±0.66) kg vs.(4.61±0.86) kg], CHD postoperative critical score (Vasoactive-Ventilation-Renal score, VVR)[(29.58±15.50) scores vs.(22.14±11.72) scores], peak blood lactate within 24 hours after surgery [(3.59±0.66) mmol/L vs.(1.71±1.13) mmol/L], postoperative blood transfusion[76.9%(20/26 cases) vs.34.5%(10/29 cases)], co-infection[53.8%(14/26 cases) vs.24.1%(7/29 cases)], cyanotic congenital heart disease [84.6%(22/26 cases) vs.34.5%(10/29 cases)] and puncture difficulty[69.2%(18/26 cases) vs.17.2%(5/29 cases)] were statistically significant(all P<0.05). Logistic regression analysis showed postoperative VVR score ( OR=0.88, 95% CI: 0.77-0.99, P=0.04), blood lactate peak within 24 hours after surgery ( OR=6.62, 95% CI: 1.35-32.46, P=0.02), and cyanotic congenital heart disease ( OR=0.04, 95% CI: 0.00-0.63, P=0.04) were risk factors for venous thrombosis in the lower extremities. Conclusions:High postoperative VVR score, high 24 h blood lactate peak after surgery and cyanotic congenital heart disease are high risk factors for puncture- or catheter-related lower extremity venous thrombosis after surgery for CHD.

The E3 ligase HERC4 is overexpressed in human breast cancer and its expression levels correlated with the prognosis of breast cancer patients. However, the roles of HERC4 in mammary tumorigenesis remain unclear. Here we demonstrate that the knockdown of HERC4 in human breast cancer cells dramatically suppressed their proliferation, survival, migration, and tumor growth in vivo, while the overexpression of HERC4 promoted their aggressive tumorigenic activities. HERC4 is a new E3 ligase for the tumor suppressor LATS1 and destabilizes LATS1 by promoting the ubiquitination of LATS1. miRNA-136-5p and miRNA-1285-5p, expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, are directly involved in suppressing the expression of HERC4. In summary, we discover a miRNA-HERC4-LATS1 pathway that plays important roles in the pathogenesis of breast cancer and represents new therapeutic targets for human breast cancer.

Objective To investigate the distribution of LAP+CD4+T cells in gastric carcinoma microenvironment and the correlation of LAP + CD4 + T cells with the progression of gastric tumor. Methods Forty gastric tumor patients and 20 healthy donors were enrolled in this study. The percentage of LAP+CD4+T cells in the peripheral blood and tumor tissue was detected by flow cytometry. The correlation of LAP+CD4+T cells with the progression of gastric tumor was analyzed. Results The percentage of LAP+CD4+T cells in the peripheral blood of gastric tumor patients was higher than that of health donors:(10.9±3.3)%vs. (4.3 ± 1.2)%;the percentage of LAP+CD4+T cells from tumor tissue was higher than that from non-tumor tissue:(13.5 ± 5.3)%vs. (4.7 ± 1.4)%. The percentage of LAP+CD4+T cells in peripheral blood from metastasis patients was higher than that from non-metastasis patients and health donors: (10.1 ± 6.4)% vs. (4.5 ± 1.3)% and (4.3 ± 1.2)%. Conclusions LAP+ CD4+ T cells accumulates in gastric carcinoma microenvironment and the percentage of LAP+CD4+T cells increases along with the progression of gastric tumor.