Assessment of monoclonal antibody glycosylation: a comparative study using HRMS, NMR, and HILIC-FLD.

Monoclonal antibodies (mAbs) represent the largest class of therapeutic protein drug products. mAb glycosylation produces a heterogeneous, analytically challenging distribution of glycoforms that typically should be adequately characterized because glycosylation-based product quality attributes (PQAs) can impact product quality, immunogenicity, and efficacy. In this study, two products were compared using a panel of analytical methods. Two high-resolution mass spectrometry (HRMS) workflows were used to analyze N-glycans, while nuclear magnetic resonance (NMR) was used to generate monosaccharide fingerprints. These state-of-the-art techniques were compared to conventional analysis using hydrophilic interaction chromatography (HILIC) coupled with fluorescence detection (FLD). The advantages and disadvantages of each method are discussed along with a comparison of the identified glycan distributions. The results demonstrated agreement across all methods for major glycoforms, demonstrating how confidence in glycan characterization is increased by combining orthogonal analytical methodologies. The full panel of methods used represents a diverse toolbox that can be selected from based on the needs for a specific product or analysis.

Case report: A novel perspective on the treatment of primary tracheal small cell carcinoma: a patient's experience with immuno-combined EP therapy and literature review.

Tracheal small cell carcinoma (SCC) is a rare malignancy, for which the optimal treatment strategy has yet to be determined. Currently, treatment largely aligns with the therapeutic guidelines established for small cell lung cancer, although numerous unresolved issues remain. This paper details a case study of a patient with Stage IIIB primary tracheal SCC, who was treated with an immune-combined etoposide-platinum(EP) regimen. This treatment offers valuable insights into innovative approaches for managing such malignancies. Furthermore, the study includes a comprehensive literature review to better contextualize the findings. The patient, admitted on May 2, 2023, had been experiencing persistent symptoms of airway discomfort for 15 days. A bronchoscopy performed on May 4 revealed tracheal SCC, classified as T4N2M0, IIIB. Following the CAPSTONE-1 study's methodology, the patient underwent six cycles of PD-L1(adebrelimab) combined with EP therapy, leading to significant relief of symptoms and the eventual disappearance of the tracheal mass.

Optimal vitamin D supplement dosage for improving insulin resistance in children and adolescents with overweight/obesity: a systematic review and network meta-analysis.

PURPOSE: We conducted a network meta-analysis which aims to evaluate the comparative efficacy of different supplementation dosages of vitamin D on cardiometabolic and bone-metabolic indicators as well as insulin resistance in children and adolescents with overweight/obesity. METHODS: Eligible studies published before December 10, 2022 were retrieved from PubMed, EMBASE, Cochrane Library, and Web of Science. Mean difference and 95% confidence interval (CI) were used to express pooled estimates. Network meta-analysis of multiple doses, including low (< 1000 IU/day, LDS), medium (1000-2000 IU/day, MDS), high (2000-4000 IU/day, HDS), and extremely high (> 4000 IU/day, EHDS) dosage strategy, was conducted using STATA/MP 14.0. RESULTS: Our network meta-analysis of 15 RCTs suggested that, compared with placebo and LDS, EHDS was increased 25-(OH)-D, with a pooled MD of 8.65 (95% CI 4.72-12.58) and 7.66 (95% CI 0.91-14.41), respectively. Meanwhile, EHDS also decreased ho meostasis model assessment-insulin resistance (HOMA-IR) (MD: - 0.74; 95% CI: - 1.45 to - 0.04) and C-reactive protein (CRP) (MD: - 18.99; 95% CI - 21.60 to - 16.38), and EHDS was also better than LDS (MD: - 18.47; 95% CI - 20.66 to - 16.28) and MDS (MD: - 19.69; 95% CI - 22.17 to - 17.21) in decreasing CRP. Ranking probability suggested that EHDS ranked best for increasing 25-(OH)-D, and decreasing HOMA-IR and CRP, with a probability of 86.1%, 83.1%, and 76.6%, respectively. CONCLUSIONS: The results of our network meta-analysis suggest that EHDS may be the best strategy for vitamin D supplementation to reduce inflammatory responses as well as improve insulin resistance in children and adolescents with overweight/obesity. PROSPERO REGISTRATION NUMBER: CRD42023387775.

Impacts of exposure to humidex on cardiovascular mortality: a multi-city study in Southwest China.

BACKGROUND: Many studies have reported the association between ambient temperature and mortality from cardiovascular disease (CVD). However, the health effects of humidity are still unclear, much less the combined effects of temperature and humidity. In this study, we used humidex to quantify the effect of temperature and humidity combined on CVD mortality. METHODS: Daily meteorological, air pollution, and CVD mortality data were collected in four cities in southwest China. We used a distributed lag non-linear model (DLNM) in the first stage to assess the exposure-response association between humidex and city-specific CVD mortality. A multivariate meta-analysis was conducted in the second stage to pool these effects at the overall level. To evaluate the mortality burden of high and low humidex, we determined the attributable fraction (AF). According to the abovementioned processes, stratified analyses were conducted based on various demographic factors. RESULTS: Humidex and the CVD exposure-response curve showed an inverted "J" shape, the minimum mortality humidex (MMH) was 31.7 (77th percentile), and the cumulative relative risk (CRR) was 2.27 (95% confidence interval [CI], 1.76-2.91). At extremely high and low humidex, CRRs were 1.19 (95% CI, 0.98-1.44) and 2.52 (95% CI, 1.88-3.38), respectively. The burden of CVD mortality attributed to non-optimal humidex was 21.59% (95% empirical CI [eCI], 18.12-24.59%), most of which was due to low humidex, with an AF of 20.16% (95% eCI, 16.72-23.23%). CONCLUSIONS: Low humidex could significantly increase the risk of CVD mortality, and vulnerability to humidex differed across populations with different demographic characteristics. The elderly (> 64 years old), unmarried people, and those with a limited level of education (1-9 years) were especially susceptible to low humidex. Therefore, humidex is appropriate as a predictor in a CVD early-warning system.

HIV associated factors among men who have sex with men in Maanshan, China: a cross-sectional study.

BACKGROUND: This study conducted a survey of men who have sex with men (MSM) in Maanshan City of Anhui Province to assess the risk behaviors related to human immunodeficiency virus (HIV) infection. METHODS: A cross-sectional survey was conducted from June 2016 to June 2019. The MSM were recruited by a peer-driven sampling method. A face-to-face interview with anonymous questionnaire was used for data collection. The information collected by the survey was summarized and epidemiology described the basic characteristics of MSM, and then the related factors were statistically analyzed. RESULTS: A total of 934 MSM were recruited with a average age was 30.5 (SD = 8.90) years old, including 816 (87.4%) HIV negative participants and 118 (12.6%) HIV positive ones. This study showed that freelancer (OR = 4.02, 95% CI: 1.96-8.23), scope of sexual partners distribution (OR = 1.78, 95% CI: 1.36-2.33), number of male sexual partners (OR = 2.11, 95% CI: 1.47-3.02), role of anal sex with men was receptive (OR = 2.54, 95% CI: 1.25-5.13) and versatile (OR = 2.34, 95% CI: 1.31-4.19) and non-steady sex partners (OR = 2.14, 95% CI: 1.56-2.93) were risk factors for HIV infection, while monthly income (OR = 0.68, 95% CI: 0.57-0.82), education level (OR = 0.79, 95% CI: 0.66-0.95), frequency of condom use (OR = 0.53, 95% CI: 0.35-0.81) and number of oral sex partners (OR = 0.35, 95% CI: 0.24-0.51) in the past 6 months were protective factors for HIV infection. CONCLUSION: Risk behaviors were common in MSM, and urgent need for targeted and comprehensive interventions to reduce risky sexual behaviour and to prevent HIV infection in MSM.

Establishment and Confirmation of a Postnatal Right Ventricular Volume Overload Mouse Model.

Right ventricular (RV) volume overload (VO) is common in children with congenital heart disease. In view of distinct developmental stages,the RV myocardium may respond differently to VO in children compared to adults. The present study aims to establish a postnatal RV VO model in mice using a modified abdominal arteriovenous fistula. To confirm the creation of VO and the following morphological and hemodynamic changes of the RV, abdominal ultrasound, echocardiography, and histochemical staining were performed for 3 months. As a result, the procedure in postnatal mice showed an acceptable survival and fistula success rate. In VO mice, the RV cavity was enlarged with a thickened free wall, and the stroke volume was increased by about 30%-40% within 2 months after surgery. Thereafter, the RV systolic pressure increased, corresponding pulmonary valve regurgitation was observed, and small pulmonary artery remodeling appeared. In conclusion, modified arteriovenous fistula (AVF) surgery is feasible to establish the RV VO model in postnatal mice. Considering the probability of fistula closure and elevated pulmonary artery resistance, abdominal ultrasound and echocardiography must be performed to confirm the model status before application.

Comprehensive N-Glycan Mapping using Parallel Reaction Monitoring LC-MS/MS.

PURPOSE: Glycan composition can impact a biotherapeutic's safety and efficacy. For example, changes in the relative abundance of different glycan attributes like afucosylation, galactosylation or high-mannose content can change the properties or functions of a monoclonal antibody (mAb). While established methods can effectively characterize major glycan species in biotherapeutic drug products, there is still a need for more sensitive and specific methods that can effectively monitor low abundance species which may impact mAb function. METHODS: Glycans released from two mAbs, adalimumab and trastuzumab, were derivatized with Rapifluor-MS™. Glycans were separated using HILIC and detected using either fluorescence (FLD) or mass spectrometry (MS). A parallel reaction monitoring (PRM) workflow was used for the MS analysis. RESULTS AND CONCLUSION: FLD analysis identified 18 and 19 glycan peaks in adalimumab and trastuzumab, respectively. Glycan identities were determined using MS-analysis and a high number of FLD peaks containing co-eluting glycan species were observed. PRM analysis quantified 38 and 39 glycan species in adalimumab and trastuzumab, respectively, and the increase in glycans that could be identified was due to superior sensitivity and selectivity compared to FLD. Notably, many low abundance glycans identified by PRM included species that were not reported in other studies. PRM also offered several additional advantages; unique structural features could be identified using the collected MS/MS spectra and de-coupling MS acquisition and data processing simplified the transfer of methods between instruments. The results established PRM as a precise, informative tool for glycan analysis and quantitation.

Mitral intervention for anomalous left coronary artery from the pulmonary artery: midterm outcomes.

OBJECTIVES: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is frequently associated with significant mitral regurgitation (MR). We aim to identify surgical outcomes in patients with or without concomitant mitral intervention. METHODS: All patients with ALCAPA who presented with >mild degree of MR at our institution between January 2008 and June 2020 were included in the retrospective study. MR recovery was defined as ≤mild MR at the last follow-up. RESULTS: The study cohort included 101 patients. The median age at repair was 7.6 months. The concomitant mitral intervention was performed in 66 patients (65%). MR grade significantly improved at the last follow-up. The cumulative incidence of MR recovery 3 years after ALCAPA repair was 34% [95% confidence interval (CI), 19-50%) in patients with mitral intervention, compared to 59% (95% CI, 41-73%) in patients without mitral intervention (P = 0.050). MR grade on postoperative day 1 was the predictor for MR recovery in patients with mitral intervention (hazard ratio, 0.080; 95% CI, 0.018-0.366; P = 0.001), whereas preoperative mitral annulus diameter z-score was the predictor in patients without mitral intervention (hazard ratio, 0.480; 95% CI, 0.232-0.993; P = 0.048). Freedom from mitral reoperation in patients with mitral intervention was 94% and 88% at 3 and 5 years after surgery, while freedom from mitral reoperation in patients without mitral intervention was 100% at both timepoints (P = 0.177). CONCLUSIONS: Despite significant MR improvement after ALCAPA repair, MR grade may not always return to normal regardless of the initial mitral management strategy, and reoperation for persistent MR is not rare.

Mid-Term Outcomes of Primary Arterial Switch Operation for Taussig-Bing Anomaly.

To identify risk factors associated with mortality and reintervention on primary arterial switch operation for Taussig-Bing anomaly in 225 cases over a 16-year period. From 2002 to 2017, 225 children with Taussig-Bing anomaly received a primary arterial switch operation at the Shanghai Children's Medical Center. Perioperative data and follow-up results were collected. Univariate and multivariable analysis was used to explore risk factors associated with early mortality. The competing risk analysis was used to identify risk factors related to reintervention. Early mortality was 12.9% (29/225) with a satisfactory long-term survival rate (10-year survival rate 85.0%). The median age at repair was 77 days (interquartile range, IQR, 48-139). The median duration of follow-up was 4.6 (range 0.1-18.3) years. 87 children (38.7%) received concomitant aortic arch repair. Prolonged cardiopulmonary bypass time (a-OR 1.18, 95% confidence interval [CI], 1.09-1.28, p < 0.001) is found to be an independent risk factor for early death. Larger weight at repair tends to be a protective factor (a-OR 0.66, 95% CI, 0.425-1.02, p = 0.060) and intramural coronary artery (a-OR 4.81, 95% CI, 0.927-24.9, p = 0.062) tends to be a risk factor for early mortality. The cumulative incidence rate of overall reintervention was 18.9% (95% CI, 10.3%-27.4%) at 5 years and 32.3% (95% CI, 17,0%-47.6%) at 10 years. No independent risk factors were identified for long-term overall reintervention. Prolonged aortic-cross clamp time was an independent risk factor for long-term right-sided reintervention (adjusted hazard ratio [a-HR] 1.12, 95% CI 1.005-1.25, p = 0.041). Neo-aortic regurgitation was a concern with an incidence rate of moderate or greater neo-AR of 16.1 % (95% CI 7.6%-24.7%) at 10 years. Intramural coronary artery remains a surgical challenge in primary arterial switch operation for the Taussig-Bing anomaly. Larger weight at ASO tends to be a protective factor for early death. Reintervention is frequently necessary but can be performed with satisfactory results.

Abnormal spinal curvature and associated factors among primary and secondary school students in Sichuan Province / 中国学校卫生

Objective@#To investigate abnormal spinal curvature among primary and secondary school students in Sichuan Province, so as to provide evidence for scientific prevention.@*Methods@#Using a stratified cluster random sampling method, a total of 210 713 students of grade 4 to grade 12 from 21 cities (prefectures) in Sichuan Province were selected for spinal curvature screening and questionnaire survey from September to November 2022. Chi-square test and multivariate Logistic regression model were used to analyze the influencing factors of abnormal spinal curvature.@*Results@#The detection rate of abnormal spinal curvature was 3.42%, with urban areas (4.54%) higher than that in suburban areas(2.57%), girls (3.86%) higher than that in boys(2.98%), high school students (4.70%) higher than that in middle school students (3.80%) and elementary school students(2.21%), the differences were statistically significant ( χ 2=606.96, 123.81, 645.24, P <0.01). Multivariate Logistic regression analysis showed that urban area, junior and senior high school, girl, carrying backpack on one shoulder, desks and chairs adjusted for student height less than ≤1 time every school year, moderate-to-vigorous physical activity less than 1 h per week, and indoors sedentary time more than 10 h/d were positively associated with abnormal spinal curvature ( OR=1.72, 1.75, 1.87, 1.26, 1.09, 1.07, 1.10, 1.25 , P <0.05).@*Conclusion@#The detection rate of abnormal spinal curvature of primary and secondary school students may be affected by the urbanicity, educational stage as well as gender in Sichuan Province. More attention should be paid to urban high school girls, and targeted strategies should be explored to reduce the incidence of abnormal spinal curvature.

Swelled Mechanism of Crumb Rubber and Technical Properties of Crumb Rubber Modified Bitumen.

Crumb rubber modified bitumen (CRMB) has excellent high-temperature performance and fatigue resistance, and is widely used in asphalt pavement to cope with increasing traffic axle load and changing climate. Under conventional preparation conditions, the swelling degree of CR can directly impact the comprehensive properties of CRMB; however, physical and chemical properties research on swelling crumb rubber (SCR) and crumb rubber recycled bitumen (CRRB) in CRMB is relatively lacking. In this paper, the working performance of CRMB and CRRB in high-temperature and low-temperature conditions were studied through physical and working performance testing of bitumen. The CR and SCR were tested by scanning electron microscope (SEM), Fourier transform infrared spectrometer (FTIR), gel permeation chromatography (GPC), and particle size distribution (PSD) tests to study the physicochemical behavior and microscopic effects before and after CR swelling. The results showed that CR dosage was in the range of 10%, 15%, and 20%, as well as that CR dosages have a positive effect on the high- and low-temperature performance, storage stability, and elastic recovery of bitumen. The high-temperature PG grades of bitumen were directly improved by four grades, and the elastic recovery rate increased by 339.9%. CR improved the ultra-low temperature crack resistance of bitumen. Due to the absorption of lighter components by CR, the relative content of the heavy component of bitumen increased; however, its low-temperature performance decreased significantly. After swelling, the CR particle size increased and the range became wider, the surface complexity of CR became higher, and the specific surface area was larger. At the same time, CR carried out the transformation process from large and medium molecules to small molecules. During the swelling process, a new benzene ring structure appeared in the CR, and the C-C bond and C-S bond of CR broke, forming part of the C=C bond.

Mucosal vaccine delivery: A focus on the breakthrough of specific barriers.

Mucosal vaccines can effectively induce an immune response at the mucosal site and form the first line of defense against microbial invasion. The induced mucosal immunity includes the proliferation of effector T cells and the production of IgG and IgA antibodies, thereby effectively blocking microbial infection and transmission. However, after a long period of development, the transformation of mucosal vaccines into clinical use is still relatively slow. To date, fewer than ten mucosal vaccines have been approved. Only seven mucosal vaccines against coronavirus disease 2019 (COVID-19) are under investigation in clinical trials. A representative vaccine is the adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV) developed by Chen and coworkers, which is currently in phase III clinical trials. The reason for the limited progress of mucosal vaccines may be the complicated mucosal barriers. Therefore, this review summarizes the characteristics of mucosal barriers and highlights strategies to overcome these barriers for effective mucosal vaccine delivery.

Role and Mechanisms of Tumor-Associated Macrophages in Hematological Malignancies.

Mounting evidence has revealed that many nontumor cells in the tumor microenvironment, such as fibroblasts, endothelial cells, mesenchymal stem cells, and leukocytes, are strongly involved in tumor progression. In hematological malignancies, tumor-associated macrophages (TAMs) are considered to be an important component that promotes tumor growth and can be polarized into different phenotypes with protumor or antitumor roles. This Review emphasizes research related to the role and mechanisms of TAMs in hematological malignancies. TAMs lead to poor prognosis by influencing tumor progression at the molecular level, including nurturing cancer stem cells and laying the foundation for metastasis. Although detailed molecular mechanisms have not been clarified, TAMs may be a new therapeutic target in hematological disease treatment.

Ross Procedure in the era of Handmade-Valved Conduits for Right Ventricular Outflow Tract Reconstruction in Children: Short-Term Surgical Outcomes.

Objective: Ross procedure is considered as the "gold standard" for aortic valve replacement, but the conduits used for right ventricular outflow tract (RVOT) reconstruction, such as homografts and bovine jugular vein (BJV) conduits, are of limited availability in China. Handmade expanded polytetrafluoroethylene-valved conduits (HVCs) have been used recently as the alternative for RVOT reconstruction, but their specific experience in Ross procedure is limited in the literature. Methods: This was a retrospective review of 27 children who underwent Ross procedure in our center from January 2018 to January 2022. Results: Mean age at surgery was 8.0 ± 3.8 years. During the study period, BJV conduits were used for RVOT reconstruction in 6 patients (22%), and HVCs were used in 21 patients (78%). Median conduit size was 20 mm (range, 16-24 mm), and mean conduit Z-score was +0.8 ± 0.9. Median time for cardiopulmonary bypass was 158 min (range, 109-275 min), and mean time for aortic crossclamping was 110 ± 21 min. There was no early mortality. During a median follow-up time of 1.4 years (range, 0.1-3.7 years), 3 patients (11%) with BJV conduits had peak conduit velocity of > 3.5 m/s; 3 patients (11%) with HVCs developed moderate conduit insufficiency; no patients had more than moderate conduit insufficiency. Three patients with BJV conduits had 5 reinterventions, and all received conduit replacement with HVCs. Conclusion: HVC is an appealing alternative to BJV conduit for RVOT construction for children undergoing Ross procedure, with favorable short-term outcomes.

Hot Deformation Behavior of the 25CrMo4 Steel Using a Modified Arrhenius Model.

25CrMo4 steel is widely used in the manufacturing of high-speed train axles due to its excellent mechanical properties. The purpose of this study is to develop an accurate modified constitutive model to describe the hot deformation behavior of the steel. Isothermal compression experiments were performed at different strain rates (0.01, 0.1, 0.5, and 1 s-1) and different temperatures (950, 1000, 1050, and 1100 °C) using a Gleeble-3800 thermal simulator. The microstructure after hot deformation was observed by the electron backscatter diffraction (EBSD), and the effects of temperature and strain rate were analyzed. The results showed that the coupling effect of temperature and strain rate on the dislocation density led to the change in the shape of the true stress-strain curve and that dynamic recovery (DRV) and dynamic recrystallization (DRX) caused the macroscopic softening phenomenon, with DRX being the main mechanism. Based on the true stress-strain curves, the strain-compensated Arrhenius constitutive model was calibrated. To improve prediction ability, a modified Arrhenius constitutive model was proposed, in which the temperature and strain rate coupling correction functions were incorporated. The original, modified Arrhenius models were evaluated according to the absolute relative error (ARE), the average absolute relative error (AARE), and the correlation coefficient (R2). Compared with the original model, the modified Arrhenius model has a higher prediction accuracy, with the ARE value mostly below 4%, the AARE value of 1.91%, and the R2 value of 0.9958.

Retinoic Acid-Induced 2 (RAI2) Is a Novel Antagonist of Wnt/ß-Catenin Signaling Pathway and Potential Biomarker of Chemosensitivity in Colorectal Cancer.

Objective: Aberrant activation of Wnt/ß-catenin signaling contributes to the maintenance of cancer stem cells and chemoresistance in colorectal cancer (CRC). Retinoic acid-induced 2 (RAI2) was proved to be a tumor suppressor in CRC in our previous report. In this study, the role of RAI2 in Wnt/ß-catenin signaling was further investigated. Methods: As a transcriptional co-regulator, C-terminal Binding Protein 2 (CtBP2) was reported to be involved in Wnt signaling in multiple and complex ways. The correlation of RAI2 and CtBP2 in CRC was analyzed by TCGA dataset, and the interaction between RAI2 and CtBP2 was explored by co-immunoprecipitation (Co-IP) in CRC cells. The effect of RAI2 on the activity of Wnt signaling and the location of ß-catenin was detected by Dual-Luciferase reporter assay and Immunofluorescence respectively. Western blotting analysis was performed to detect the expression of target genes involved in Wnt signaling. Sphere formation assay was employed to detect the effect of RAI2 on stem cell like properties. Cell viability assay was used to detect the chemosensitivity of cells before and after transfection of RAI2. Results: The interaction between RAI2 and CtBP2 was confirmed by Co-IP in CRC cells. Besides, the negative correlation of RAI2 and CtBP2 in CRC was found by analyzing the TCGA dataset. Re-expression of RAI2 in human colon cancer cells (HCT116 and LoVo) suppressed the fluorescent activity of Wnt signaling, increased the phosphorylation and inhibited nuclear translocation of ß-catenin, with down-regulation of target genes like c-Myc, CyclinD1, ASCL2, and LGR5. In contrast, the mutated RAI2, which can't interact with CtBP2, has no above effects. We observed low expression of RAI2 in 33.89% (101/298) of CRC patients, which was significantly associated with reduced phosphorylation of ß-catenin (r=0.8866, P<0.0001), poor 5-year relapse-free survival (RFS) (P = 0.0029) and overall survival (OS) (P = 0.0102). Restoration of RAI2 in HCT116 and LoVo cells inhibited stem cell-like properties of CRC cells and increased chemosensitivity of these cells to oxaliplatin and fluorouracil. Conclusion: Low expression of RAI2 can serve as an independent poor prognostic marker. RAI2 inhibits Wnt signaling by interacting with or down-regulating CtBP2, resulting in repression of stem cell-like properties and increased chemosensitivity of CRC cells.

Midterm Surgical Outcomes for ALCAPA Repair in Infants and Children.

BACKGROUND: Surgical correction of an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) has been associated with excellent survival during recent years. The purpose of this study was to evaluate the effectiveness of reimplantation of the coronary artery and to investigate the recovery of postoperative cardiac and mitral valve (MV) function. METHODS: From 2005 to 2015, 80 patients who had ALCAPA received surgical correction. Among them, 49 were infants. The median patient age was 7.8 months. Operative strategies included reimplantation of the coronary artery in 71 patients, the Takeuchi procedure in another 7 patients, and coronary artery ligation in the remaining 2 patients. RESULTS: There were 11 hospital deaths and 2 late deaths. Six patients required intraoperative or postoperative mechanical circulatory support. A significant improvement in the ejection fraction (EF) and shortening fraction (SF) was present in all surviving patients at discharge, at a 3-month follow-up and at a 1-year follow-up. MV function improved gradually after surgical repair with no late secondary intervention. CONCLUSIONS: The repair of ALCAPA can be accomplished by establishment of a dual-coronary system, which offers an acceptable mortality rate and will rarely require a second surgery. Left ventricular (LV) recovery is a progressive process, especially for infants with impaired LV function. Concomitant MV annuloplasty is safe and reliable and can be performed as necessary in patients with moderate or severe mitral valve regurgitation.

Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage.

Background: Pulmonary regurgitation caused by the correction or palliation of pediatric tetralogy of Fallot (TOF) leads to chronic right ventricular (RV) volume overload (VO), which induces adolescent RV dysfunction. A better understanding of the molecular mechanism by which VO initiates neonatal RV remodeling may bring new insights into the post-surgical management of pediatric TOF. Methods and Results: We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 1 (P1) using a rat model to induce neonatal VO. Echocardiography revealed that the velocity and velocity- time-integral of the pulmonary artery (PA) were significantly elevated, and hematoxylin and eosin (H&E) staining showed that the diameter of the RV significantly increased. RNA-seq analysis of the RV on P7 indicated that the top 10 enriched Gene Ontology (GO) terms and the top 20 enriched terms in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were associated with immune responses. Flow-cytometric analysis demonstrated that the number of CD4+and CD8+ immune cells were significantly augmented in the VO group compared with the sham group. Conclusions: A neonatal cardiac VO rat model on P1 was successfully created, providing a platform for studying the molecular biology of neonatal RV under the influence of VO. VO - induces an immune response at the neonatal stage (from P1 to P7), suggesting that immune responses may be an initiating factor for neonatal RV remodeling under the influence of VO and that immunosuppressants may be used to prevent pediatric RV remodeling caused by VO.

Chronic Stress Activates PlexinA1/VEGFR2-JAK2-STAT3 in Vascular Endothelial Cells to Promote Angiogenesis.

It is known that chronic stress modulates multiple processes in a complex microenvironment, such as angiogenesis and immune function. However, the role of chronic stress inducing tumor angiogenesis and how it contributes to tumor progression are not quite clear. The following study assess psychological state from numerous ambulatory cancer cases (n=332), and chronic stress-related hormone levels were further measured. Here, we show that chronic stress not only causes behavioral changes in human, most importantly attributed to an elevated level of stress-related hormones. To address this, isoprenaline, the agonist of ß2-adrenergic receptor (ß2-AR), was utilized for simulating chronic stress and demonstrating the mechanism of stress in tumor angiogenesis at molecular level both in vivo and in vitro. As suggested by this study, isoprenaline promote VEGF autocrine of HUVECs, which can induce plexinA1 and VEGFR2 expression. Moreover, we show that isoprenaline promoted the expression of p-JAK2 and p-STAT3 in vitro. The results reveal that, isoprenaline enhances the autocrine of VEGF in HUVECs and up-regulating plexinA1 and VEGFR2 levels, thus activating the phosphorylation of JAK2-STAT3 pathway, the two essential parts during angiogenesis. The present work indicates that, the mechanism of chronic stress in enhancing angiogenesis is probably achieved through activating the plexinA1/VEGFR2-JAK2-STAT3 signal transduction pathway within HUVECs, and this is probably a candidate target for developing a strategy against angiogenesis in cancer.

Association Between Preoperative Factors and In-hospital Mortality in Neonates After Cardiac Surgery in China.

Background: Little is known about preoperative factors affecting cardiac surgery outcomes of neonates in China. We sought to examine the association between characteristics of neonates with congenital heart disease (CHD) and early postoperative outcomes after cardiac repair in a tertiary care paediatric hospital. Methods: A single-centre retrospective cohort study of neonates who underwent cardiac surgery between January 2006 and December 2019 was performed. Demographic, institutional, and surgical characteristics of neonates were examined and their association with in-hospital mortality was analysed using multivariable logistic regression models. Results: During the study period, we analysed the outcomes of 1,078 neonates. In-hospital mortality decreased to 13.8% in the era 2017-2019. The overall in-hospital mortality rate was 16.3%. Normal weight at surgery [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.47-0.85; P = 0.003] was associated with lower mortality risk. Poor health status (emergent: OR, 3.11; 95% CI, 1.96-4.94; P < 0.001; elective: OR, 1.63; 95% CI, 1.11-2.40; P = 0.013), higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) categories (STAT 5 category: OR, 2.58; 95% CI, 1.04-6.43; P = 0.042), and limited individual surgeon experience (surgeon with 5-10 operations per year: OR, 1.43; 95% CI, 1.06-1.95; P = 0.021) were associated with higher odds of early death. Conclusion: In-hospital mortality after neonatal cardiac surgery remained high in our centre over the past 10 years. Some preoperative aspects, including low-weight at surgery, poor health status, increased surgical complexity, and limited surgeon experience were significantly associated with higher mortality. Based on the observed associations, the necessary practises to be modified, especially in preoperative care, should be identified and assessed in future research.