Association of underweight and obesity with adverse postoperative renal outcomes in infants and young children undergoing congenital heart surgery.

Postoperative acute kidney injury (AKI) is a prevalent condition and associated with increased morbidity and mortality following cardiac surgery. This study aimed to investigate the association of underweight and obesity with adverse postoperative renal outcomes in infants and young children undergoing congenital heart surgery. This retrospective cohort study included patients aged from 1 month to 5 years who underwent congenital heart surgery with cardiopulmonary bypass at the Second Xiangya Hospital of Central South University from January 2016 to March 2022. On the basis of the percentile of body mass index (BMI) for age and sex, eligible participants were divided into three nutritional groups: normal bodyweight, underweight (BMI P5), and obesity (BMI P95). Primary outcomes included postoperative AKI and major adverse kidney events within 30 days (MAKE30). Multivariable logistic regression was performed to determine the association of underweight and obesity with postoperative outcomes. The same analyses were reproduced for classifying patients using weight-for-height instead of BMI. A total of 2,079 eligible patients were included in the analysis, including 1,341 (65%) patients in the normal bodyweight group, 683 (33%) patients in the underweight group, and 55 (2.6%) patients in the obesity group. Postoperative AKI (16% vs. 26% vs. 38%; P < 0.001) and MAKE30 (2.5% vs. 6.4% vs. 9.1%; P < 0.001) were more likely to occur in the underweight and obesity groups. After adjusting for potential confounders, underweight (OR1.39; 95% CI 1.08-1.79; P = 0.008) and obesity (OR 3.85; 95% CI 1.97-7.50; P < 0.001) were found to be associated with an increased risk of postoperative AKI. In addition, both underweight (OR 1.89; 95% CI 1.14-3.14; P = 0.014) and obesity (OR 3.14; 95% CI 1.08-9.09; P = 0.035) were independently associated with MAKE30. Similar results were also found when weight-for-height was used instead of BMI.    Conclusion: In infants and young children undergoing congenital heart surgery, underweight and obesity are independently associated with postoperative AKI and MAKE30. These results may help assess prognosis in underweight and obese patients, and will guide future quality improvement efforts. What is Known: • Postoperative acute kidney injury (AKI) is prevalent and associated with increased morbidity and mortality following pediatric cardiac surgery. • Major adverse kidney events within 30 days (MAKE30) have been recommended as a patient-centered endpoint for evaluating AKI clinical trajectories. A growing concern arises for underweight and obesity in children with congenital heart disease. What is New: • Prevalence of underweight and obesity among infants and young children undergoing congenital heart surgery was 33% and 2.6%, respectively. • Both underweight and obesity were independently associated with postoperative AKI and MAKE30 following congenital heart surgery.

Exploring the binding mechanism and functional properties of lactoferrin-berberine complex: Based on multispectral analysis, molecular docking, and dynamics simulations.

Denaturation and/or aggregation of proteins under adverse environmental conditions can greatly impair their bioactivity and functional properties. Based on this, this study aims to improve the functional properties of lactoferrin by complexing with berberine and investigate the mechanism using multispectral techniques, molecular docking and dynamics simulations. The results showed that berberine bound to lactoferrin through hydrogen bonding and van der Waals forces and altered its conformation, surface hydrophobicity, amino acid microenvironment, and secondary structure. Molecular docking and dynamics simulations further revealed that berberine inhibited the drastic changes in the lactoferrin structure, contributing to the complex stability. Consequently, the denaturation temperature and degradation temperature (224 °C to 230 °C) and the tolerance to extreme pH, high temperature, and ions of the lactoferrin-berberine complex were improved. This study systematically revealed the mechanism of berberine to improve the functional properties of lactoferrin, contributing to the development and application of novel functional ingredients.

Innate immunity and primary biliary cirrhosis: activated invariant natural killer T cells exacerbate murine autoimmune cholangitis and fibrosis.

UNLABELLED: Murine models of autoimmunity allow the study of the earliest events in disease pathogenesis. Our laboratory has developed a xenobiotic induced model of primary biliary cirrhosis (PBC) following immunization of mice with 2-octynoic acid coupled to bovine serum albumin (2-OA-BSA), an antigen selected following quantitative structure-activity relationship analysis of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the immunodominant autoantigen of PBC. Recent data in humans with PBC has suggested that a major component of liver pathology is due to activation of innate immunity. We took advantage of our 2-OA-BSA model and immunized mice with and without the addition of α-galactosylceramide (α-GalCer), an invariant natural killer T cell activator. Importantly, we report herein that 2-OA-BSA-immunized mice exposed to α-GalCer develop a profound exacerbation of their autoimmune cholangitis, including significant increases in CD8(+) T-cell infiltrates, portal inflammation, granuloma formation, and bile duct damage. Furthermore, such mice produce increased levels of antimitochondrial antibodies and have evidence of fibrosis, a feature not previously reported in the murine models of PBC. CONCLUSION: Our data suggests a primary role of innate immunity in the exacerbation of autoimmune cholangitis and also become a logical explanation for the recurrence of PBC following liver transplantation in the absence of major histocompatability complex compatibility. We submit that PBC begins with loss of tolerance to PDC-E2 and a multilineage antimitochondrial response in which autoreactive CD8(+) T cells are critical. However, the perpetuation of disease and its exacerbation will also be modulated by innate immune mechanisms.

Gene therapy for allergic diseases.

Allergic diseases, such as allergic asthma, allergic rhinitis, atopic dermatitis, conjunctivitis, urticaria, food allergy, and/or anaphylaxis, are associated with the skewing of immune responses towards a T helper 2 (TH2) phenotype, resulting in eosinophilic inflammation. TH2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13, promote IgE production, mast cell differentiation, and eosinophil growth, migration and activation which then lead to the pathologic abnormalities in allergic diseases. Moreover, the impaired function of regulatory T cells has been noted in allergic diseases. To date, treatments for allergic diseases, such as antihistamines, corticosteroids, bronchodilators and some allergen-specific immunotherapy, are effective but costly and require long-term and recurrent drug administration. Gene therapy has been shown to be an easy, effective, and convenient treatment by delivering the allergen or the therapeutic protein in the form of plasmid DNA in vivo to modulate allergic immune responses. We summarize here the recent advances of gene therapy in allergic diseases and discuss the challenges in clinical application.

Omega-3 polyunsaturated fatty acids and reduction of depressive symptoms in older adults: A systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to systematically review the efficacy of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplements in reducing depressive symptoms among older adults aged 60 and above. METHODS: Relevant electronic databases were searched from their inception to June 4, 2018, including Medline, Embase, Web of Science, Cochrane Library, PsycINFO, Global Health, CINAHL, ClinicalTrials.gov and Chinese Biomedical Medicine Database. Two reviewers independently screened for eligible studies, extracted data, and assessed risk of bias of the included studies. The effect size data were analyzed using robust variance estimation in meta-regression. RESULTS: Nine studies were included. The overall treatment effects of n-3 PUFA supplements in reducing depressive symptoms for older adults was not statistically significant (d = -0.202, 95% CI = -0.463, 0.060). Meta-regression found interventions with dosage of n-3 PUFA greater than 1.5 g/d had an average effect size of -0.428, with a 95% confidence interval of [-0.822, -0.035], which is statistically significant. Meta-regression did not find significant moderating effects of comorbidity, baseline depression, intervention duration, and EPA-DHA ratio, potentially due to limited statistical power. LIMITATIONS: The current review only included 9 studies based on literature search in major English and Chinese databases, which provided limited statistical power for moderator analysis and the results are suggestive only. CONCLUSIONS: The meta-analysis of 9 RCTs found mixed findings of the efficacy of n-3 PUFA in the treatment of depressive symptoms among older adults aged 60 and above. More high-quality, large-scale RCTs are needed to confirm the current conclusions.