Spiritual needs and communicating about death in nonreligious theistic families in pediatric palliative care: A qualitative study.

BACKGROUND: Spiritual support should be offered to all patients and their families regardless of their affiliated status with an organized religion. AIM: To understand nonreligious theistic parents' spirituality and to explore how parents discuss death with their terminally ill children in mainland China. DESIGN: Qualitative study. SETTING/PARTICIPANTS: This study was conducted in the hematology oncology center at Beijing Children's Hospital. Participants in this study included 16 bereaved parents. RESULTS: Participants described themselves as nonreligious but showed a tendency toward a particular religion. Parents sought religious support in the face of the life-threatening conditions that affected their child and regarded the religious belief as an important way to get psychological and spiritual comfort after experiencing the death of their child. Religious support could partially address parents' spiritual needs. Parents' spiritual needs still require other supports such as bereavement services, death education, and family support groups. Some parents stated that it was difficult to find a way to discuss death with their children. For patients who come from nonreligious theistic families, their understanding of death was more complex and may be related to atheism. CONCLUSION: Religious support could be an element of spiritual support for nonreligious theistic parents of terminally ill children. Multiple strategies including religious supports and nonreligious supports should be rationally integrated into spiritual support of nonreligious theistic family. Patient's personal belief in death should be assessed before discussing death with them.

Reliability and validity of the Chinese mandarin version of PedsQL™ 3.0 transplant module.

BACKGROUND: Long-term health-related quality of life (HRQoL) of pediatric patients after hematopoietic stem cell transplantation (HSCT) is increasingly studied worldwide. However, few studies have been performed in China, where no uniform scale is available; the PedsQL™ Cancer Module 3.0 Chinese Mandarin version has been used to evaluate HRQoL of patients after HSCT in China. This study aimed to assess the reliability and validity of the Chinese Mandarin version of PedsQL™ 3.0 Transplant Module. METHODS: Patients between 2 and 18 years old, who underwent HSCT from January 2006 to June 2014, were recruited in Beijing Children's Hospital affiliated to Capital Medical University, the First Affiliated Hospital of Southern Medical University and Beijing Daopei Hospital. 207 parent reports and 182 child self-reports of the PedsQL™ 3.0 Transplant Module Chinese Mandarin version were assigned, of which 362 were returned. RESULTS: No missing item response was observed in the returned reports. Cronbach's alpha coefficient exceeded 0.7 in total scale and every dimension. The intraclass correlation coefficient exceeded 0.8 in all dimensions of child self-reports and parent reports. Spearman's rank correlation coefficients of items and their respective dimensions were 0.6-0.94 in parent reports, and 0.62-0.93 in child self-reports, while a weak association was found between the items and other dimensions. Exploratory factor analysis indicated a good extraction effect, and construct validity of the scale was >60 %. CONCLUSIONS: The Chinese Mandarin version of PedsQL™ 3.0 Transplant Module has good feasibility, reliability and validity. Its use may help improve the HRQoL of children after HSCT in China.

Restricted feeding regimens improve white striping associated muscular defects in broiler chickens.

The current study investigated the effects of intermittent feeding (IF) and fasting strategies at different times post-hatch on muscle growth and white striping (WS) breast development. In the first trial, 32 one-day-old Abor Acre broilers were fed ad libitum (AL) for 3 d post-hatch and then randomly allotted into 4 feeding strategies including AL, 1h-IF group (1 h IF, 4 times feeding/d, 1 h each time), 1.5h-IF (1.5 h IF, 4 times feeding/d, 1.5 h each time), and fasting (1d acute fasting, 6 d free access to feed) groups and fed for 7 d. Although angiogenic genes including VEGFA, VEGFR1, and VEGFR2, and myogenic genes including MYOG and MYOD were upregulated (P < 0.05), the breast muscle satellite cell (SC) number and PAX7, MYF5 expression were decreased by the IF strategies (P < 0.05). One-day fasting at 6 d of age also upregulated angiogenic genes and MYOD expression (P < 0.05), downregulated MYF5 expression (P < 0.05), but did not change SC number (P > 0.05). In the second trial, 384 one-day-old birds were fed AL for 1 wk and then randomly allotted to the above 4 feeding strategies starting at 8 d of age until 42 d of age. Similarly, IF and fasting strategies upregulated the expression of angiogenic and myogenic genes (P < 0.05). Both 1h-IF and 1.5h-IF increased breast muscle SC number (P < 0.05). At slaughter, breast muscle fiber diameter of 1.5h-IF was smaller but the SC number was larger than that of the birds fed AL (P < 0.05). The IF and fasting strategies prevented WS development, and reduced breast WS scores and triglyceride content (P < 0.05) without changing the body weight (P > 0.05). Fasting and 1h-IF reduced the expression of adipogenic genes ZNF423 and PDGFRα (P < 0.05). Moreover, IF and fasting strategies reduced fibrosis in breast muscle and reduced skeletal muscle-specific E3 ubiquitin ligases (TRIM63 and MAFBX) (P < 0.05). Fasting significantly reduced CASPASE-3 in breast muscle (P < 0.05). In conclusion, IF starting in the first week decreases SC number. Compared to AL, IF or fasting promotes muscular angiogenesis, increases SC number, prevents muscle degeneration, and prevents the development of WS without impairing the growth performance of broiler chickens.

Whole-body adipose tissue multi-omic analyses in sheep reveal molecular mechanisms underlying local adaptation to extreme environments.

The fat tail of sheep is an important organ that has evolved to adapt to extreme environments. However, the genetic mechanisms underlying the fat tail phenotype remain poorly understood. Here, we characterize transcriptome and lipidome profiles and morphological changes in 250 adipose tissues from two thin-tailed and three fat-tailed sheep populations in summer and winter. We implement whole-genome selective sweep tests to identify genetic variants related to fat-tails. We identify a set of functional genes that show differential expression in the tail fat of fat-tailed and thin-tailed sheep in summer and winter. These genes are significantly enriched in pathways, such as lipid metabolism, extracellular matrix (ECM) remodeling, molecular transport, and inflammatory response. In contrast to thin-tailed sheep, tail fat from fat-tailed sheep show slighter changes in adipocyte size, ECM remodeling, and lipid metabolism, and had less inflammation in response to seasonal changes, indicating improved homeostasis. Whole-genome selective sweep tests identify genes involved in preadipocyte commitment (e.g., BMP2, PDGFD) and terminal adipogenic differentiation (e.g., VEGFA), which could contribute to enhanced adipocyte hyperplasia. Altogether, we establish a model of regulatory networks regulating adipose homeostasis in sheep tails. These findings improve our understanding of how adipose homeostasis is maintained, in response to extreme environments in animals.

Pediatric acute myeloid leukemia patients with KMT2A rearrangements: a single-center retrospective study.

PURPOSE: Pediatric acute myeloid leukemia (AML) with KMT2A rearrangements has a very different prognosis. Poor outcomes cannot be avoided even after hematopoietic stem cell transplantation. In order to investigate the prognosis and efficacy, we conducted a retrospective analysis. PATIENTS AND METHODS: We retrospectively analyzed a total of 32 children with KMT2A rearrangements AML treated in our hospital between January 2015 and February 2021. RESULTS: The proportion of patients with KMT2A-rearranged in the medium-risk group of overall survival (OS) and event-free survival (EFS) was 100%. No differences in OS, EFS and cumulative incidence of relapse (CIR) were detected between the haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and full matched HSCT (P = 0.289, P = 0.303, P = 0.303). Acute graft-versus-host disease (aGVHD) was often detected in the haplo-HSCT cohort, while full matched HSCT had no obvious aGVHD, assessed as≤1 grade (P < 0.05). Patients in the medium-risk pediatric group could acquire 100% OS and EFS only after chemotherapy. There was no significant difference in OS, EFS and CIR between full matched HSCT and haploidentical transplantation in pediatric AML with KMT2A rearrangements, but full matched HSCT seemed to have a lower death rate. The severity of aGVHD in the full matched HSCT was less than that in the haploidentical transplantation group. CONCLUSION: The primary choice of donor can be HLA-matched sibling donors or matched unrelated donors for children with AML with KMT2A rearrangements, and the secondary choice can be haploid donors.

Neonatal vitamin A administration increases intramuscular fat by promoting angiogenesis and preadipocyte formation.

To explore the effects and underlying mechanism of vitamin A on beef marbling fat development, angus steers were injected vitamin A at birth and 1 month of age and in vitro experiments were performed to investigate the effects of retinoic acid (RA) on angiogenesis and adipogenesis of intramuscular stromal vascular (SVF) cells. Results showed that vitamin A administration increased the intramuscular PDGFRα+ adipose progenitors, improved adipogenic potential of intramuscular SVF cells and dramatically upregulated VEGFA. At slaughter, vitamin A increased intramuscular triacylglycerols by 45% without affecting overall fatness. In a 3D culture system, RA promoted capillary sprout development and promoted the subsequent adipogenesis of intramuscular SVF cells by activating VEGFA/VEGFR2 signaling. However, during terminal adipogenesis, RA downregulated PPARγ, C/EBPα and inhibited lipid accumulation. In conclusion, vitamin A/RA upregulate VEGFA and stimulate intramuscular vascular capillary development, which increases intramuscular adipose progenitors and contributes to adipocyte formation. When administrated at neonatal stage, vitamin A promotes beef marbling development without affecting overall fatness.

Allogeneic hematopoietic stem cell transplantation with the modified myeloablative conditioning regimen for children with chronic active Epstein-Barr virus infection.

Importance: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the only effective treatment for chronic active Epstein-Barr virus infection (CAEBV). The clinical efficacy and safety of allo-HSCT with different conditioning regimens in children with CAEBV remain unclear. Objective: To evaluate the effectiveness and safety of allo-HSCT with the modified myeloablative conditioning (MAC) regimen for children with CAEBV and also the factors affecting the outcomes. Methods: We retrospectively analyzed children with CAEBV who underwent allo-HSCT with the modified MAC regimen at Beijing Children's Hospital, Capital Medical University from October 2016 to June 2021. Data related to the clinical manifestations, engraftment, and outcome were extracted from the medical records. Results: The cohort comprised 41 patients (24 males, 17 females) with a median transplantation age of 92.6 (60.4, 120.7) months and a median follow-up time of 28.2 (15.3, 40.2) months. Four patients (9.8%) died, among which three died from primary disease relapse, and one died from grade IV acute graft-versus-host diseases (aGVHD) after stopping treatment. The 3-year overall survival (OS) and 3-year event-free survival (EFS) rates were 88.8% ± 5.4% and 85.0% ± 5.7%, respectively. The 3-year OS and EFS did not significantly differ between the patients with hemophagocytic lymphohistiocytosis (HLH) and the patient without HLH (87.7% ± 6.8% vs. 91.7% ± 8.0%, P = 0.790; 85.0% ± 6.9% vs. 84.6% ± 10.0%, P = 0.921), or among the patients with complete remission, partial remission, and activity disease before HSCT (all P > 0.05). Multivariate analysis showed that grade III-IV aGVHD was a risk factor for mortality (Hazards ratio: 11.65, 95% confidence interval: 1.00, 136.06; P = 0.050). Interpretation: Allo-HSCT with the modified MAC regimen is safe and effective for pediatric CAEBV. This treatment benefits patients with HLH or active disease. Patients with Grade III-IV aGVHD may be associated with worse outcomes.

Development levels of pediatric palliative care teams and the extent of palliative care understanding and implementation among pediatric oncologists in China.

IMPORTANCE: Pediatric palliative care (PPC) is an interdisciplinary collaboration that focuses on the prevention and relief of patient suffering. PPC has emerged as a critical field of medical expertise and practice. However, no information is available regarding the progress of PPC in the Chinese mainland. OBJECTIVE: This study investigated the geographic distribution, team structure, and services of PPC teams in the Chinese mainland. It also investigated the level of understanding and implementation among pediatric oncologists regarding PPC. METHODS: The PPC subspecialty group of the Pediatrics Society of the Chinese Medical Association included 45 PPC teams. The team structure and services were investigated using questionnaires mailed to the team leader of each PPC team. In addition, we sent questionnaires regarding the level of PPC understanding and implementation of PPC practices to 170 pediatric oncologists in 11 hospitals. RESULTS: The geographical distribution of PPC teams is uneven in China. Most PPC teams are concentrated in the eastern provincial capital of China. Most PPC teams had limited staff and services. The level of PPC understanding was considerably limited across all demographics; most pediatric oncologists reported "some understanding" (n = 71, 41.8%) or "poor understanding" (n = 50, 29.4%). Only 62.9% of pediatric oncologists had experience providing advice to family members regarding PPC matters. INTERPRETATION: China is currently experiencing a critical shortage of PPC resources. Most pediatric oncologists had a limited understanding of PPC and reported limited practical implementation of PPC, which leads to underutilization of PPC resources.

Haploidentical haematopoietic stem cell transplantation for malignant infantile osteopetrosis and intermediate osteopetrosis: a retrospective analysis of a single centre.

OBJECTIVE: To evaluate the clinical efficacy of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) for the treatment of malignant infantile osteopetrosis (MIOP) and intermediate osteopetrosis. METHODS: Children with MIOP and IOP who underwent haplo-HSCT in Beijing Children's Hospital, Capital Medical University, from January 2010 to May 2018 were retrospectively analysed. Data relating to the clinical manifestations, engraftment, and prognosis of the children were extracted from medical records. RESULTS: Twenty-seven patients, including 18 males and 9 females, with an onset age of 12 (0.04-72) months were enrolled in this study. The median time from diagnosis to transplantation was 4 (1-23) months. All patients received haplo-HSCT with a myeloablative conditioning regimen (including fludarabine, busulfan, and cyclophosphamide). Graft versus host disease (GVHD) prophylaxis was based on anti-human T lymphocyte porcine immunoglobulin/anti-human thymus globulin, methotrexate, and mycophenolate mofetil. The median observation time was 55.2 (0.3-126.2) months. By the end of follow-up, twenty patients survived and seven patients died. The 5 year overall survival rate was 73.9%. Stage I-II acute GVHD was observed in 20 patients, stage III GVHD in 1 patient and no patients had stage IV disease. Chronic GVHD was observed in 11 patients (40.7%) and was controlled by anti-GVHD therapy. CONCLUSIONS: Haplo-HSCT was an effective treatment for MIOP and IOP, with a high survival rate and significantly improved clinical symptoms. For patients with a vision impairment before HSCT, the improvement was slow after transplantation. The incidence of GVHD was high but mild and was effectively controlled by appropriate treatment. These data indicated that haplo-HSCT was a feasible treatment for MIOP and IOP.

Haploidentical hematopoietic stem cell transplantation for pediatric patients with chronic active Epstein-Barr virus infection: a retrospective analysis of a single center.

BACKGROUND: This study aimed to evaluate the feasibility and clinical effect of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for the treatment of pediatric patients with chronic active Epstein-Barr virus infection (CAEBV). METHODS: Children with CAEBV who did not have matched donors and underwent haplo-HSCT in Beijing Children's Hospital, Capital Medical University, from October 2016 to June 2020 were analyzed retrospectively. Data relating to the clinical manifestations, engraftment, and prognosis of the children were extracted from medical records. RESULTS: Twenty-five patients, including 16 males and 9 females, with an onset age of 5.0 ± 2.6 years and a transplantation age of 6.9 ± 2.9 years, were enrolled in this study. The mean time from diagnosis to transplantation was 3.8 (2.0-40.2) months. The mean observation time was 19.0 ± 12.0 months. Three patients received the reduced intensity conditioning regimen, and the remaining patients all received the modified myeloablative conditioning regimen. By the end of the follow-up, 23 patients were characterized by disease-free survival (DFS), 22 were characterized by event-free survival (EFS), and two died. One of the patients died of thrombotic microangiopathy (TMA), and another died of graft versus host disease (GVHD); this patient discontinued the treatment for economic reasons. The 3-year overall survival (OS) rate was estimated to be 92.0% ± 5.4%, and the 3-year EFS rate was estimated to be 87.4% ± 6.8%. All active patients survived after HSCT event-free. Acute GVHD degrees 1-3 were observed in ten patients (40.0%), and degree IV was observed in six (24.0%), who were all cured except for one patient. Chronic GVHD was observed in nine (36.0%), and most of these cases were mild. The incidence of TMA and veno-occlusive disease (VOD) was 28.0% and 4.0%. CONCLUSIONS: Haploidentical hematopoietic stem cell transplantation is safe and effective in the treatment of pediatric CAEBV and can be used as an alternative therapy without matched donors or emergency transplantation. Patients with active disease before HSCT also benefited from haplo-HSCT. Haplo-HSCT requires careful monitoring for complications, such as GVHD and TMA. Early detection of TMA and timely treatment can reduce mortality and can improve the survival rate.

Cognitive and psychological outcomes of pediatric allogeneic hematopoietic stem cell transplantation survivors in a single center in China.

To investigate the cognitive and psychological outcomes of pediatric allogeneic HSCT survivors in China.A total of 135 3 to 18 years old children and adolescents who underwent allo-HSCT and survived at least 3 months post-HSCT were recruited and completed the assessments. Cognitive and psychological functions were assessed via age-appropriate standardized measures. Clinical information was extracted from the medical records.Forty one 3 to 6 years old children completed Psychological Questionnaires for 3 to 6 years Children. The scores of 21(51.2%) children in cognitive development dimension, 18(43.9%) in motor development dimension, 16(39.0%) in language development and social development dimension, 15(36.6%) in emotion and will dimension and 14(34.1%) in living habits dimension were less than the standard. Fifty six 8 to 16 years old children and adolescents completed the Depression Self-rating Scale for Children and 9 (16.1%) of these met the criteria of depression. Sixty nine 7 to 16 years old children and adolescents completed the screening for Child Anxiety Related Disorders and 7 (10.1%) of these met the criteria of anxiety, especially social phobia and school phobia. Eighty nine 6 to 18 years old children and adolescents completed the Symptom Checklist-90 and 43.8% to 77.5% of these experienced mild symptoms like obsession-compulsion (77.5%), hostility (64%), and interpersonal sensitivity (60.7%). Children treated with total body irradiation (TBI) showed more cognitive impairments like motor deficits than those without TBI. Also older children and adolescents had more symptoms like psychoticism.These findings demonstrated cognitive and psychological late effects of pediatric allo-HSCT survivors in a single center in China and highlighted that the survivors conditioned with TBI had more cognitive impairments and older children and adolescents had more symptoms. Early intervention in these children and adolescents might minimize the cognitive losses and psychological effects.