Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression. / æ²‰é»˜ä¿¡æ¯è°ƒèŠ‚å› å­2åœ¨èƒ†ç®¡ç™Œä¸­çš„è¡¨è¾¾åŠå ¶å¯¹å¯åˆ‡é™¤èƒ†ç®¡ç™Œæ‚£è€ é¢„åŽçš„é¢„æµ‹ä»·å€¼.

OBJECTIVES: To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma (CCA) based on the expression of silence information regulator 2 (SIRT2). METHODS: The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases. Gene set enrichment analysis (GSEA) was used to explore potential mechanisms of SIRT2 in CCA. The expression of SIRT2 protein in CCA tissues and normal tissues (including 44 pairs of specimens) was also detected by immunohistochemistry (IHC) in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021. The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed. A survival prediction model for patients with resectable CCA was constructed with COX regression results, the calibration curve and the time-dependent receiver operating characteristic curve (ROC) were used to evaluate the performance of the constructed model, and the predictive power between this model and the American Joint Committee on Cancer (AJCC)/TNM staging system (8th edition) was compared. RESULTS: SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases. IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues. GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway, such as fatty acid metabolism, oxidative phosphorylation and amino acid metabolism. SIRT2 expression was related to serum triglycerides level, tumor size and lymph node metastasis (all P<0.05). The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival (OS) than patients with lower SIRT2 expression (P<0.05). Univariate COX regression analysis suggested that pathological differentiation, clinical stage, postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients (all P<0.05). Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients (both P<0.05). A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed. The C-index of the model was 0.675, and the area under the time-dependent ROC curve (AUC) for predicting survival in the first, second, and third years was 0.879, 0.778, and 0.953, respectively, which were superior to those of AJCC/TNM staging system (8th Edition). CONCLUSIONS: SIRT2 is highly expressed in CCA tissues, which is associated with poor prognosis in patients with resectable CCA. The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system (8th edition) in prediction of survival of postoperative CCA patients.

[Methylselenocysteine Promotes Etoposide Cytotoxicity by Enhancing Homotypic Gap Junctions Composed of Connexin 26].

Objective: To investigate the effect of methylselenocysteine (MSC) on the function of homotypic gap junction (GJ) composed of connexin (Cx) 26 and its regulation of chemotherapeutic drug cytotoxicity. Methods: The Tet-on HeLa cells transfected with and stably expressing Cx26 were used as the tool cells. Effects of MSC on cell growth, GJ function, and Cx26 protein expression were examined by MTT method, parachute assay, and Western blot analysis, respectively. The cytotoxicity of chemotherapeutic drugs was determined by standard colony-forming assay, and the relationship between MSC's effect on cytotoxicity of these chemotherapeutic drugs and its regulation of GJ was further analyzed. Results: In Tet-on HeLa cells, doxycycline (Dox) can induce the expression of Cx26, which could then form functional GJs. Within a concentration range of 50 µmol/L, MSC had no significant effect on HeLa cell growth. Non-toxic concentrations of MSC can enhance GJs in a concentration-dependent manner and exert its effect at the nanomolar level. This effect was associated with an induction of Cx26 protein expression by MSC. Among the three common chemotherapeutic agents with different mechanisms of action, etoposide (Eto) presented cytotoxicity differences between HeLa cells cultured at low density (nonconfluent, no GJ formed) and high density (confluent, GJ formed). What's more, the inhibitory effect of Eto combined with MSC on HeLa cell colony formation was stronger than that of Eto alone, and this effect occurred only in HeLa cells with GJ formation. Conclusion: MSC can potentiate the cytotoxicity of Eto by enhancing the GJs composed of Cx26, indicating that combined strategy of selenide and chemotherapy shows potential value in the treatment of malignant tumors.

Value of pulmonary annulus index in predicting transannular patch in tetralogy of Fallot repair.

OBJECTIVE: It is very important to accurately assess the transannular patch (TAP) in the surgical treatment of tetralogy of Fallot (TOF). The pulmonary annulus index (PAI; the actual pulmonary annulus diameter divided by the expected pulmonary annulus diameter), GA ratio (the ratio of pulmonary annulus and aortic annulus), PAAI (the ratio of pulmonary annulus cross-section and aortic annulus cross-section), and pulmonary annulus Z score (PA Z score) were compared. This study aimed to analyze and explore the application value of PAI in predicting the need for TAP in children undergoing TOF repair. METHODS: In total, 130 patients who were diagnosed with TOF and underwent TOF repair in Beijing Anzhen Hospital affiliated to Capital Medical University from December 2018 to December 2019 were retrospectively studied. In total, 112 cases were included in this study and 18 cases were excluded, of which 16 cases were aged above 18 years and 2 cases suffered from Down syndrome. They were divided into TAP group and no TAP group; the values of the pulmonary annulus and aortic annulus were measured. GA ratio, PAI, PAAI, the pulmonary annulus Z score, and main pulmonary artery (MPA) Z score were calculated to perform statistical analysis. RESULTS: A total of 112 patients were included in the study, aged 4-177 months, with an average of 22.87 ± 30.21 months; 66 males and 46 females; weighing 5.3-29 kg, with an average of 9.94 ± 4.08 kg; three cases died, one case died of sepsis caused by pulmonary infection, one case died of low cardiac output syndrome, and one case died of multiple organ failure. In total, 62 cases (55.8%) did not undergo TAP and 50 cases (44.2%) underwent TAP. The pulmonary annulus Z score, main pulmonary artery Z score, and PAI in the TAP group were smaller than those in the no TAP group (p < .05). Receiver operating curve (ROC) analysis showed that when the cut-off value of pulmonary annulus was -1.98, the area under the curve (AUC) was 0.88, the sensitivity was 80%, and the specificity was 71%; when the cut-off value of PAI was 0.53, AUC was 0.85, the sensitivity was 75%, and the specificity was 80%; when the cut-off value of GA ratio was 0.55, AUC was 0.85, the sensitivity was 76%, and the specificity was 80%. The area under the PAAI curve was 0.85, the sensitivity was 76%, and the specificity was 79%. When the pulmonary valve Z score, PAI, GA ratio, PAAI, and MPA Z score were all greater than the dividing value, TAP was avoided in more than 90% of children with TOF. When the pulmonary valve Z score, PAI, GA ratio, PAAI, and the main pulmonary artery Z score were all below the dividing value, more than 90% of children with TOF needed TAP. CONCLUSION: The predictive effect of PAI as a simple and effective predictor of TAP in TOF radical operation is the same as that of pulmonary annulus Z score, and combining it with the main pulmonary artery Z score was the most accurate method of prediction.

Extremely Stretchable Vitrimers.

Vitrimers are covalent adaptable networks, having many interesting versatile abilities with unprecedented potentials. Here, the combination of a low-Tg polymer system with dioxaborolane metathesis is used to develop catalyst-free vitrimers that can be stretched to more than 8900× their original length at a moderate stretching rate (≈50 mm min-1 ). Superstretchable vitrimers are prepared from biodegradable xylitol-based polyol oligomers and cross-linked by dioxaborolane linkages. They are also found to be remarkable in terms of mechanical strength and other properties, such as malleability, self-healing ability, puncture resistance, and processing stability. Furthermore, the repeated rearrangements of dioxaborolane linkages and hydrogen bonds give rise to efficient energy dissipation with a maximum efficiency of 88%, allowing the superstretchable vitrimers to be promising for energy absorbing applications.

Analysis of clinical features of heart failure in children with cardiomyopathy and improved ejection fraction.

Background: The prognosis of children with heart failure varies considerably. After treatment, left ventricular ejection fraction (LVEF) can be improved in some children. The aim of this study was to analyze the clinical features of children with heart failure accompanied by cardiomyopathy and recovered ejection fraction [heart failure with recovered ejection fraction (HFrecEF)] and to identify the predictors of improved LVEF. Methods: Children diagnosed with heart failure in Beijing Anzhen Hospital Affiliated to Capital Medical University from 2018 to 2021 were retrospectively enrolled. According to the baseline and change of LVEF, the patients were divided into two groups: a reduced ejection fraction (HFrEF) group and an HFrecEF group. The t-test was used to evaluate the difference between the two groups. The predictive factors of ejection fraction improvement were analyzed with a logistic regression model. Results: A total of 72 children were included in this study, including 31 (43.1%) in the HFrEF group and 41 (56.9%) in the HFrecEF group. Compared with children in the HFrEF group, children in the HFrecEF group were younger and had faster resting heart rates, lower creatinine, lower suppression of tumorigenicity 2 (ST2) expression, a lower platelet-to-lymphocyte (PLT:LYM) ratio, and smaller left atrial diameter. After a mean follow-up of 35.87 months, 26 cases returned to normal ejection fraction. In the HFrEF group, sudden cardiac death occurred in two cases, and four cases received heart transplantation. Logistic analysis showed that virus infection [odds ratio (OR) =1.279; 95% confidence interval (CI): 0.374-4.379; P=0.007], low ST2 expression (cutoff value =1.89 ng/mL: OR =1.042; 95% CI: 1.007-1.082; P=0.032), and treatment with intravenous immunoglobulin (IVIG) (OR =5.077; 95% CI: 1.458-17.684; P=0.011) were predictors of improvement in LVEF in patients with heart failure after treatment. Conclusions: In some patients with HFrecEF, LVEF eventually returned to normal. The combination of viral infection, low ST2 expression, and the application of IVIG therapy were found to be independent predictors of LVEF improvement in patients with heart failure after treatment.

A Retrospective Study of 1,526 Cases of Transcatheter Occlusion of Patent Ductus Arteriosus.

BACKGROUND: Patent ductus arteriosus (PDA) is one of the most common congenital heart diseases and began to get treated by transcatheter occlusion since 1997 in China. Since then, several devices have been invented for occluding PDA. This study aimed to evaluate the technical feasibility, safety, and efficacy of transcatheter occlusion of PDA with different devices. METHODS: One thousand five hundred and twenty-six patients (537 boys, 989 girls) with PDA from January 1997 to September 2014 underwent descending aortogram and transcatheter occlusion procedure. We retrospectively analyzed data of these patients, including gender, age, weight, size and morphology of PDA, and devices used in transcatheter occlusion, outcomes, and postoperational complications. RESULTS: Median age and median weight were 4.0 years (range: 0.3-52.0 years old) and 15.3 kg (range: 4.5-91.0 kg), respectively. Mean ductal diameter, aortic ductal diameter, ductal length, and pulmonary artery pressure were 3.50 ± 2.15 mm, 10.08 ± 2.46 mm, 7.49 ± 3.02 mm, and 30.21 ± 17.28 mmHg, respectively. Morphology of PDA assessed by descending aortogram was of type A in 1428 patients, type B in 6 patients, type C in 79 patients, type D in 4 patients, and type E in 9 patients according to the classification of Krichenko. Of all the 1526 patients, 1497 patients underwent transcatheter PDA closure, among which 1492 were successful. Devices used were Amplatzer duct occluder I (ADO I, 1280, 85.8%), Cook detachable coils (116, 7.8%), ADO II (ADO II, 68, 4.6%), muscular VSD occluder (12, 0.8%), and Amplatzer vascular plug (16, 1.0%). CONCLUSIONS: Excellent occlusion rates with low complication rates were achieved with all devices regardless of PDA types. With transcatheter occlusion technique and devices developing, more patients with PDA can be treated with transcatheter closure both safely and efficiently.

Two congenital coronary abnormalities affecting heart function: anomalous origin of the left coronary artery from the pulmonary artery and congenital left main coronary artery atresia.

BACKGROUND: The anomalous origin of the left coronary artery (LCA) from the pulmonary artery (ALCAPA) and congenital left main coronary artery atresia (CLMCA-A) are two kinds of very rare coronary heart diseases which affect heart function profoundly. This study aimed to retrospectively illustrate the clinical features and therapy experience of ALCAPA and CLMCA-A patients. METHODS: From April 1984 to July 2012, in Beijing Anzhen Hospital, 23 patients were diagnosed with ALCAPA and 4 patients with CLMCA-A. We summarized the clinical data of the 27 cases and retrospectively analyzed the clinical manifestation, diagnosis, and treatments of these two kinds of congenital coronary abnormalities. RESULTS: The 23 patients (13 males and 10 females, aged ranging from 2.5 months to 65 years) identified with ALCAPA were classified into infantile type (age of onset younger than 12 months, 16 cases) and adult type (age of onset older than 12 months, 7 cases). Four patients were diagnosed with CLMCA-A (three males and one female, aged ranging from 3 months to 2 years). The main clinical manifestations of infantile-type ALCAPA and CLMCA-A include repeated respiratory tract infection, heart failure, dyspnea, feeding intolerance, diaphoresis, and failure to thrive. And these two congenital coronary abnormalities might be misdiagnosed as endocardial fibroelastosis, dilated cardiomyopathy, and acute myocardial infarction. As for the adult-type ALCAPA, cardiac murmurs and discomfort of the precordial area are the most common presentations and might be misdiagnosed as coronary heart disease, myocarditis, or patent ductus arteriosus. In ECG examination: Infantile-type ALCAPA and CLMCA-A showed abnormal Q waves with T wave inversion in leads I, avL, and V4-V6, especially in lead avL. However, ECG of adult-type ALCAPA lacked distinct features. In chest radiography: pulmonary congestion and cardiomegaly were the most common findings in infantile-type ALCAPA and CLMCA-A, while pulmonary artery segment dilation was more common in adult type. In echocardiography, the common features of infantile-type ALCAPA and CLMCA-A included left ventricular enlargement, left ventricular systolic function normal or mildly reduced in CLMCA-A or significantly reduced in ALCAPA, and moderate to large mitral valve. It was performed in 9 of 23 cases of ALCAPA and showed the origin of the dilated right coronary artery (RCA) from the right sinus of the aortic root and absence of LCA origin in angiography. After opacification of RCA, reverse flow in the LCA and pulmonary artery was visualized through coronary artery collateral circulation. Angio was performed in three of the four cases of CLMCA-A and showed left main coronary artery was a blind end, with diameter of only 1.1-2.0 mm. Treatment and prognosis: 21 patients with ALCAPA had cardiac surgery and 6 of them died postoperatively. Fifteen postoperative patients survived without overt symptoms within the follow-up period of 6-166 months (median 17 months). As for treatment of CLMCA-A, four patients took digoxin and diuretics without undergoing cardiac surgery. Their clinical symptoms improved during the close follow-ups. CONCLUSIONS: ALCAPA and CLMCA-A are two rare coronary artery abnormalities that affect cardiac function in infants and children. In younger patients with cardiomegaly and heart dysfunction these two congenital coronary diseases should be noticed.