Reliability and validity of the Chinese version of the PedsQL Multidimensional Fatigue Scale in children with acute leukemia

Background:The PedsQL Multidimensional Fatigue Scale(PedsQL^(TM)MFS)is widely used to rate fatigue in children living in English-speaking countries.However,insufficient instruments are available to conduct parallel assessment on fatigue in parents and children in China.In this regard,an appropriate measurement method must be developed.Objectives:This study aims to determine the reliability and validity of the Chinese-language PedsQL^(TM)MFS.Methods:Children with cancer(n=125)and their parents were surveyed in Guangzhou,China.The parents of children aged 2e4 years completed the PedsQL^(TM)MFS proxy reports,whereas the other children and their parents completed the questionnaires by themselves.Results:The PedsQL^(TM)MFS-Chinese version demonstrated satisfactory internal consistency reliability(child self-report Cronbach's a=0.87;parent self-report Cronbach's a=0.93).The factor loadings of the items ranged from 0.78 to 0.87 for general fatigue,0.56e0.78 for sleep/rest fatigue,and 0.62e0.89 for cognitive fatigue.Conclusion:This study proves that the PedsQL^(TM)MFS-Chinese version is an effective tool for screening fatigue in Chinese children with cancer.

Hedgehog signaling in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment

The Hedgehog(HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment(TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance.The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6(IL-6) and interferon-g(IFN-g), macrophages, and T cell-dependent immune responses, play a vital role in tumor growth by affecting the HH signaling pathway. Moreover, inhibition of proliferating cancer-associated fibroblasts(CAFs) and inflammatory factors can normalize the TME by suppressing HH signaling. Furthermore, aberrant HH signaling activation is favorable to both the proliferation of cancer stem cells(CSCs) and the drug resistance of gastrointestinal tumors. This review discusses the current understanding of the role and mechanism of aberrant HH signaling activation in gastrointestinal carcinogenesis, the gastrointestinal TME,tumor immune tolerance and drug resistance and highlights the underlying therapeutic opportunities.

Gene therapy for neurodegenerative disorders:advances, insights and prospects

Gene therapy is rapidly emerging as a powerful therapeutic strategy for a wide range of neurodegenerative disorders, including Alzheimer’s disease(AD), Parkinson’s disease(PD) and Huntington’s disease(HD). Some early clinical trials have failed to achieve satisfactory therapeutic effects. Efforts to enhance effectiveness are now concentrating on three major fields: identification of new vectors,novel therapeutic targets, and reliable of delivery routes for transgenes. These approaches are being assessed closely in preclinical and clinical trials, which may ultimately provide powerful treatments for patients. Here, we discuss advances and challenges of gene therapy for neurodegenerative disorders,highlighting promising technologies, targets, and future prospects.

VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses

Diabetic nephropathy(DN)is considered the primary causes of end-stage renal disease(ESRD)and is related to abnormal glycolipid metabolism,hemodynamic abnormalities,oxidative stress and chronic inflammation.Antagonism of vascular endothelial growth factor B(VEGF-B)could effi-ciently ameliorate DN by reducing renal lipotoxicity.However,this pharmacological strategy is far from satisfactory,as it ignores numerous pathogenic factors,including anomalous reactive oxygen species(ROS)generation and inflammatory responses.We found that the upregulation of VEGF-B and downregulation of interleukin-22(IL-22)among DN patients were significantly associated with the progression of DN.Thus,we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS.To meet these challenges,a novel anti-VEGFB/IL22 fusion protein was developed,and its therapeutic effects on DN were further studied.We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses via the inhibition of renal oxidative stress and mitochondrial dysfunction.Moreover,the fusion protein could also improve diabetic kidney disease by increasing insulin sensitivity.Collectively,our findings indicate that the bifunctional VEGF-B antibody and IL-22 fusion protein could improve the progression of DN,which highlighted a novel therapeutic approach to DN.