Guangzhou Women & Childrens Medical Center

Identifying the definition of “being a good parent” facilitates the understanding of parents’ personal beliefs and deeds regarding their ill child.

The aim of this study was to explore the concept of “being a good parent to my ill child” during pediatric cancer treatment from the perspective of Chinese children, parents, and providers.

A descriptive qualitative study was conducted with 6 children, 18 parents, 5 doctors, 19 nurses, and 3 social workers by semistructured interviews at 3 Chinese hospitals.

Except for “letting the Lord lead,” 7 themes from the original conceptual model were validated, for example, “being there for my child” (n = 51, 100.0%); “doing right by my child” (n = 38, 74.5%), “being an advocate for my child” (n = 27, 52.9%), “conveying love to my child” (n = 26, 51.0%), “making my child healthy” (n = 18, 35.3%), “being a good life example” (n = 13, 25.5%), and “not allowing suffering” (n = 13, 25.5%). A new theme, “rebuilding myself” (n = 39, 76.5%), emerged in the Chinese context. “Being a good parent to my ill child” is perceived differently among stakeholders. Healthcare professionals’ facilitation to fulfill the concept included “recognizing the individualized good-parent definition,” “providing best available care” and “establishing a supportive environment.”

“Being a good parent to my ill child” is meaningfully expressed by Chinese parents and recognized by children and providers during pediatric cancer treatment.

It is important to support parents in conveying their internal good parent definition and sharing it with stakeholders. Attention should be paid to related cultural influencers, a supportive family-friendly environment, and shared decision making involving the child’s voice.

Ovarian cancer (OCa) remains a highly lethal disease, largely due to late-stage diagnosis and limited treatment options for recurrent metastatic tumors. Long non-coding RNAs (lncRNAs) have been recognized as key regulators of cancer hallmarks, yet their specific roles in driving OCa progression are not fully understood. In this study, we employed an integrated approach combining clinical correlation, functional assays, and mechanistic investigations to reveal that lncRNA ZFHX2-AS1 is significantly downregulated in OCa tissues and cells, with its reduced expression associated with poor clinical outcomes. Using in vitro and in vivo models, we demonstrated that overexpression of ZFHX2-AS1 suppresses OCa cell proliferation, migration and invasion, whereas ZFHX2-AS1 knockdown enhances these malignant phenotypes. Mechanistically, we defined that ZFHX2-AS1 interacts with and attenuates the enzymatic activity of the pseudouridine synthase DKC1, thereby reducing pseudouridylation and stabilizing the oncogenic ARHGAP5 mRNA. Re-expression of ARHGAP5 could partially reverse the tumor-suppressive effects of ZFHX2-AS1. Further, we found that ARHGAP5 promotes epithelial-mesenchymal transition (EMT) by regulating Rho GTPases activities, and that ZFHX2-AS1 inhibits EMT in OCa by downregulating ARHGAP5 expression and suppressing the Rho GTPase signaling pathway. Taken together, our findings identify ZFHX2-AS1 as a potent tumor suppressor in OCa, acting through the modulation of DKC1-mediated pseudouridylation of ARHGAP5 and the inhibition of the Rho GTPase pathway, thus offering a potential therapeutic target for combating OCa progression.

Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).

Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro–B-type natriuretic peptide) was an exploratory end point.

A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (N=187) or enalapril (N=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47–0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72–1.14]; P =0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children.

In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks.

URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02678312.