Identification of target behavior in process of intervention for children with feeding difficulty and relevant factors in randomized controlled trial

Objective To identify the target behavior in the process of behavioral intervention for children with feeding difficulty and relevant factors that may contribute to more effective intervention.Methods Children aged from 1 to 6 years with feeding difficulty randomly received interactive behavioral intervention(245 cases)or routine primary care(217 cases).By the end of the 1,3,6,and 9 months,the rating score of feeding difficulty and the body mass index(BMI)were assessed.The target behavior was determined based on the selecting criteria that simultaneously satisfied two conditions:①it was relevant to improving children's nutritional status;②it changed fast during intervention.Moreover,the relevant factors of target behavior were analyzed by multivariate analysis(Multi-Way ANOVA).Results Among nine behaviors of feeding difficulty,"eating slowly"was identified as a target behavior because it was closely relevant to the BMI z-score increment and had the biggest score reduction at early stage during intervention.Various factors were relevant to improving the target behavior,including parents acting as caregivers,caregiver's education level equal to and above junior college,and caregiver's concern about their children's feeding difficulty.Conclusion"Eating slowly"should be selected as the target behavior for early intervention for children with feeding difficulty and some social factors should be considered for optimizing the intervention.

Preliminary Evaluation of Hemodynamic Effects of Fontan Palliation on Renal Artery Using Computational Fluid Dynamics

Background:The assessment of renal function is important to the prognosis of patients needing Fontan palliation due to the reconstructed compromised circulation.To know the relationship between the kidney perfusion and hemodynamic characteristics during surgical design could reduce the risk of acute kidney injury(AKI)and the postoperative complications.However,the issue is still unsolved because the current clinical evaluation methods are unable to predict the hemodynamic changes in renal artery(RA).Methods:We reconstructed a three-dimensional(3D)vascular model of a patient requiring Fontan palliation.The technique of computational fluid dynamics(CFD)was utilized to explore the changes of RA hemodynamics under different possible blood flow rates.The relationship between the kidney perfusion and hemodynamic characteristics was investigated.Results:The calculated results indicated the declined tendency of the pressure and pressure drop as the flow rate decreased.When the flow rate decreased to two-thirds of its baseline,both the pressure of left renal artery(LRA)and the pressure of right renal artery(RRA)dipped below 50%,and the pressure of RRA fell more quickly than that of LRA.Uneven distribution of WSS was observed on the trunk of RA,and the lowest WSS was found at the distal of RA.The average WSS in RA dropped to around 50%as the flow rate reached one-third of its baseline.Conclusions:As a promising approach,CFD can be utilized to quantitatively evaluate the hemodynamic characteristics of RA and contribute to offsetting the drawbacks of clinical assessments of renal function,to help realize better prognosis for the patients with Fontan palliation.

Long-Range Electronic Effect-Promoted Ring-Opening Polymerization of Thioctic Acid to Produce Biomimetic Ionic Elastomers for Bioelectronics

Poly(disulfide)s have been widely used in flexible wearable electronics,smart materials,and drug delivery.The synthesis of poly(disulfide)s usually utilizes external stimuli or toxic initiators to promote the polymerization.Here,we indicated that the long-range electronic effect can significantly alter the reactivity of the disulfide group.Accordingly,we established deprotonation-promoted ring-opening polymerization of thioctic acid(TA)as a highly effective and simple method to synthesize poly(disulfide)s due to the long-range electronic effect and nucleophilic carboxylate.Without external stimuli and initiators,simple mixing of TA and deprotonation reagent,choline bicarbonate,in different ratios at room temperature rapidly produced a series of high molecular weight(up to 772 kDa)ionic liquid crystal poly(disulfide)s elastomers with room temperature self-healing ability,adjustable conductivity(2.39×10^(−2)∼0.28×10^(−2)S m^(−1)),degradability,biocompatibility,antibacterial property,and tissue-like softness(Young’s moduli ranging from 18.2±6.0 to 111.1±36.7 kPa).The experiments and density functional theory calculations also revealed the principle of long-range electronic effect to establish a new synthetic strategy of poly(disulfide)s with superior properties favorable for bioelectronics.

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

Background:Liver cancer is largely resistant to chemotherapy.This study aimed to identify the effective chemotherapeutics forβ-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1(CTNNB1),the most frequently altered proto-oncogene in hepatic neoplasms.Methods:Constitutiveβ-catenin-activated mouse embryonic fibroblasts(MEFs)were established by deleting exon 3(β-catenin^(Δ(ex3)/+)),the most common mutation site in CTNNB1 gene.A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibitedβ-catenin^(Δ(ex3)/+)but not for wild-type MEFs.Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis.The efficacy and selectivity of methotrexate(MTX)onβ-catenin-activated human liver cancer cells were determined in vitro.Immuno-deficient nude mice subcutaneously inoculated withβ-catenin wild-type or mutant liver cancer cells and hepatitis B virus(HBV);β-catenin^(lox(ex3)/+)mice were used,respectively,to evaluate the efficacy of MTX in the treatment ofβ-catenin mutant liver cancer.Results:MTX was identified and validated as a preferential agent against the proliferation and tumor formation ofβ-catenin-activated cells.Boosted nucleotide synthesis was the major metabolic aberration inβ-catenin-active cells,and this alteration was also the target of MTX.Moreover,MTX abrogated hepatocarcinogenesis of HBV;β-catenin^(lox(ex3)/+)mice,which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer.Conclusion:MTX is a promising chemotherapeutic agent forβ-catenin hyperactive liver cancer.Since repurposing MTX has the advantages of lower risk,shorter timelines,and less investment in drug discovery and development,a clinical trial is warranted to test its efficacy in the treatment ofβ-catenin mutant liver cancer.

A Novel Mutation of Notch homolog protein 2 gene in a Chinese Family with Hajdu-Cheney Syndrome

Hajdu-Cheney syndrome （HCS） is a rare disorder which is characterized by developmental delay, craniofacial anomalies, congenital heart defects, hearing deficit, polycystic kidneys, and bone abnormalities, including progressive osteoporosis, acroosteolysis, wormian bones, and abnormal bonefractures.

Optimized RNA interference therapeutics combined with interleukin-2 mRNA for treating hepatitis B virus infection

This study aimed to develop a pan-genotypic and multifunctional small interfering RNA(siRNA)against hepatitis B virus(HBV)with an efficient delivery system for treating chronic hepatitis B(CHB),and explore combined RNA interference(RNAi)and immune modulatory modalities for better viral control.Twenty synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and evaluated.The lipid nanoparticle(LNP)formulation was optimized by adopting HO-PEG_(2000)-DMG lipid and modifying the molar ratio of traditional polyethylene glycol(PEG)lipid in LNP prescriptions.The efficacy and safety of this formulation in delivering siHBV(tLNP/siHBV)along with the mouse IL-2(mIL-2)mRNA(tLNP/siHBVIL2)were evaluated in the rAAVHBV1.3 mouse model.A siRNA combination(terms“siHBV”)with a genotypic coverage of 98.55%was selected,chemically modified,and encapsulated within an optimized LNP(tLNP)of high efficacy and security to fabricate a therapeutic formulation for CHB.The results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA(up to 3log_(10)reduction;vs PBS)in dose-and time-dependent manners at single-dose or multi-dose frequencies,with satisfactory safety profiles.Further studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus,via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4^(+)and CD8^(+)T cell responses by expressed mIL-2 protein.By adopting tLNP as nucleic acid nanocarriers,the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV,thus offering a promising translational therapeutic strategy for treating CHB.