Objective:To construct A novel scoring model of immune signatures for colon cancer based on machine learning,which improve the survival prediction and immune therapy.Methods:Screening immune signatures from 1 301 immune-related genes(IRG)by the combined strategy of Lasso+bootstrap+multi Cox to calculate IRG scores of colon cancer patients from TCGA databases,and comprehensive the differences on function,prognostic status and immune therapy between high IRG scores group and IRG scores group.Results:Groups based on IRG scores were significantly different on the prognostic status of colon cancer patients,which were validated by other independent datasets.The IRG scores also could assess the effect of immune therapy of colon cancer.Conclusion:This study provides ideas for immune therapy and researches of colon cancer based on immune genes,and IRG scores can be used to assess the prognosis of colon cancer patients.

Objective To explore the value of multimodal MRI in evaluating the efficacy of retinoblastoma(RB)after selective ophthalmic artery infusion(SOAI)in children.Methods The MRI and clinical data of 80 children with intraocular RB with monocu-lar disease after chemotherapy were collected.The changes of MRI parameters in children with successful and failed eye protection before and after chemotherapy was analyzed.Results After chemotherapy,the maximum tumor diameter and △ SI were significantly reduced,the distance between tumor and optic disc and apparent diffusion coefficient(ADC)were significantly increased,the calcifi-cation/tumor ratio was increased,and the change of eyeball size was not obvious in the children with successful eye protection com-pared with before treatment.After chemotherapy,the maximum tumor diameter and the range of retinal detachment were significantly increased,and the cross-sectional area of the eyeball was significantly reduced,and △ SI,ADC and calcification/tumor ratio were not significantly changed compared with before treatment in the children with failed eye protection.Conclusion Multimodal MRI can accu-rately evaluate the effectiveness of chemotherapy in children and provide conclusive evidence for the formulation of subsequent treat-ment plans.

Objective This study aims to systematically evaluate the experiences of patients with hematologic neoplasm undergoing chimeric antigen receptor T-cell(CAR-T)therapy and nursing care,and to provide a reference basis for healthcare providers to develop personalized intervention strategies.Methods PubMed,Web of Science,Embase,CINAHL,Cochrane Library,PsycINFO,Scopus,Australia Joanna Briggs Institute(JBI)EBP Database,China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP Database,and China Biology Medicine(CBM)Database were systematically searched for qualitative studies on the experiences of patients with hematologic neoplasm undergoing CAR-T therapy and nursing care.The search period extended up to September 2023.The quality of the literature was reviewed according to the JBI Qualitative Assessment and Review Instrument,and a pooled analysis was applied to integrate the results.Results A total of 15 studies were included,generating 76 findings,which were then organized into 8 categories,resulting in 3 integrated findings.(1)Patients experienced conflicting emotions,with expectations often at odds with reality,leading to emotional fluctuations:expectations about treatment were entangled with concerns about risks;emotions fluctuated with expectations and actual experiences.(2)Patients experienced physical and social functional impairments,but as the disease eased,normal functioning recovered:rapid decline and improvement in physical functions;loss and recovery of social functions.(3)Patients desired access to professional guidance and psychosocial support.Conclusion Patients undergoing CAR-T therapy often contend with emotional conflicts.Changes in physical and social functions after the completion of treatment result in needs for seeking comprehensive medical and nursing support.It is recommended that healthcare providers conduct dynamic assessments and interventions regarding patients'emotional states before treatment,focus on early identification and management of adverse reactions after treatment,and offer continuous nursing services after discharge to enhance patients'confidence in participating in CAR-T therapy and improve their overall quality of life.

Objective To observe the expression of ciz1 in human colorectal cancer tissues and analyse the relationship between their expression and clinicopathologic features.Methods We detected the expression of Ciz1 and Ciz1 mRNA by immunohistochemistry and Western blotting.The relationship between the expression of ciz1 and clinicopathologic features was analied.Results According to immunohistochemical results,Ciz1 showed significant high expression in the primary lesion of colorectal cancer tissue,compared to normal adjacent tissues(66.7%vs.35.0%,P=0.001).Through Western blot analysis,it was found that the relative expression level in colorectal cancer tissue was 0.32±0.03,while in normal colorectal mucosal tissue it was 0.11±0.01.In addition,the relative expression level of Ciz1 in colorectal cancer tissue was significantly higher than that in normal intestinal mucosal tissue(P<0.05).The study found that the overexpression of Ciz1 in colorectal cancer tissue is significantly correlated with the T stage(P=0.018),lymph node metastasis(P=0.022),and AJCC stage(P=0.017)of the cancer.The age,gender,tumor location,degree of differentiation,and the presence of distant metastasis of patients were not correlated with this(P>0.05).The expression level of Ciz1 in colorectal cancer tissue is significantly increased,which is closely related to the T stage(P=0.018),lymph node metastasis(P=0.022),and American Joint Committee on Cancer stage(P=0.017)of colorectal cancer.Conclusion This association suggests that Ciz1 may play an important role in tumor staging,participating in the development and spread of tumors.Therefore,it can be foreseen that Ciz1 is expected to become a new biomarker for evaluating the prognosis of colorectal cancer patients.

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism.MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.

Phenome-wide association study (PheWAS) is a reverse genetic analysis method to identify the potential phenotypes associated with genetic variations. With the increasing availability of biomedical databases and electronic medical records (EMR), PheWAS has gradually become an effective tool to unveil the relationships between exposure and a broad range of health phenotypes. The unique advantage of this method is that it can simultaneously explore the associations of a specific exposure with a variety of disease outcomes, thus helping to reveal multiple causal relationships and the shared pathogenic mechanisms among diseases. However, PheWAS has limitations, including selecting instrumental variables and the heavy burden of various corrections. In addition, how to interpret the biological mechanisms underlying significant findings is another crucial issue of PheWAS. This review will focus on the methodology and application of PheWAS to provide meaningful suggestions and insights for future studies.

Parental perceptions of child vulnerability (PPCV) is widespread among pediatric patients, and has serious adverse effects on children, families, and society. This article reviews the concept, commonly used measurement tools, and research status of PPCV at home and abroad, and summarizes the influencing factors from three aspects, namely, pediatric factors, parental factors and social factors. This article analyzes the limitations of existing research and makes recommendations, with a view to providing references for future evaluation, prevention and intervention of PPCV.

Objective:To investigate the genetic characteristics of norovirus (NoV) in children with acute gastroenteritis in Shanghai.Methods:A total of 709 stool specimens were collected from outpatients with acute gastroenteritis in Children′s Hospital of Shanghai from October 2018 to September 2019. Real-time RT-PCR was used for qualitative detection of NoV, and RT-PCR was used to identify the genotypes of NoV with the primers of VP1 gene, RdRp region and RdRp-VP1 region. SPSS20.0 statistical software was used for data processing and bioinformatics software was used for homology, phylogenetic and recombination analysis of NoV gene sequences.Results:NoV was detected in 265 out of the 709 stool specimens with a positive rate of 37.4%. Sequence analysis of RdRp region and VP1 gene showed that seven different genotypes including GⅡ.P16-GⅡ.2, GⅡ.P12-GⅡ.3, GⅡ.Pe-GⅡ.4_Sydney 2012, GⅡ.P7-GⅡ.6, GⅡ.P8-GⅡ.8, GⅡ.P21-GⅡ.13 and GⅡ.P17-GⅡ.17 were detected from 111 NoV-positive specimens. The predominated genotype was GⅡ.P16-GⅡ.2 (30.6%, 34/111), followed by GⅡ.Pe-GⅡ.4_Sydney 2012 (27.0%, 30/111) and GⅡ.P12-GⅡ.3 (24.3%, 27/111). Two new NoV recombinant strains belonging to GⅡ.P21-GⅡ.13 genotype were identified and the recombination site was in the junction region of ORF1 and ORF2. NoV infection occurred every month, but the predominant genotype was different. No significant difference in the positive rates of NoV was found between male and female patients ( P=0.329). However, there were significant differences between different age groups ( P=0.011) and the children in the age groups of >11-12 years old and >2-3 years old had higher rates of NoV infection. Conclusions:The predominated recombinant NoV strains belonged to GⅡ.P16-GⅡ.2, GⅡ.Pe-GⅡ.4_Sydney 2012 and GⅡ.P12-GⅡ.3 genotypes, and two new recombinant NoV strains (GⅡ.P21-GⅡ.13) were found in Shanghai during October 2018 to September 2019. Gene sequencing across ORF1 and ORF2 was conducive to better understanding the NoV genotypes and recombination.

Objective:To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase.Methods:From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy.Results:The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) ( P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy ( P<0.001) and longer duration of imatinib therapy ( P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions:Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.