Purpose To observe the changes in the brain microstructure of children with global developmental delay(GDD)via MR diffusion kurtosis imaging(DKI).Materials and Methods A total of 34 children with GDD were included as the experimental group,and 34 children with normal development as the control group in the Third Affiliated Hospital of Zhengzhou University from September 2020 to March 2023,retrospectively.DKI and clinical data were collected.After post-processing,DKI parameters were obtained,including fraction anisotropy,mean kurtosis(MK),axial kurtosis and radial kurtosis(Kr).The differences in parameters in each region of interest of the two groups were analyzed,the correlation between DKI parameters and Gesell developmental scale was analyzed,and the receiver operating characteristic curve was drawn to analyze the diagnostic efficacy of DKI parameters.Results Compared with the control group,the MK value of the centrum semiovale decreased(Z=-2.723,P<0.01),the MK value and Kr value of the thalamus decreased(t/Z=-3.220,-3.128,both P<0.01),the MK value and axial kurtosis value of the anterior and posterior limb of internal capsule decreased(t/Z=-2.958,-2.573,-2.085,-2.403,all P<0.05),the Kr value of the anterior limb of internal capsule decreased(t=-2.155,P<0.05),the MK value and Kr value of frontal white matter decreased(Z=-2.177,-2.711,both P<0.05).The correlation analysis showed that the MK and Kr value of the anterior limb of the internal capsule and the MK value of the posterior limb of the internal capsule were positively correlated with the score of the gross motor functional area(r=0.379,0.378,0.405,all P<0.05),and the MK value of the posterior limb of the internal capsule was positively correlated with the fine motor functional area(r=0.461,P=0.006).The Kr value of the thalamus had the largest area under the curve at 0.721 when diagnosing GDD.Conclusion Children with GDD have changes in brain microstructure,and DKI has a certain value for diagnosis.

This study intends to establish a colorectal cancer(CRC)organoid model,expand and isolate CRC-reactive tumor-infiltrating lymphocytes(TILs),screen tumor-specific T cell receptors(TCRs)and perform functional verification,in order to provide a technological platform and research foundation for the clinical transformation of individualized adoptive T-cell immunotherapy for colorectal cancer.An organoid model derived from colon cancer patient tissues was constructed using in vitro 3D culture techniques,which then subjected to HE staining and immunohistochemistry for detecting morphological characteristics and representative molecular expression.Subsequently,CRC organoids were co-cultured with TILs for sorting reactive TILs using flow cytometry,and the characteristics of reactive TCR clones was analyzed through single T cell receptor gene cloning technology.Furthermore,the function of TCRs was verified through cytotoxicity experiments.Morphological analysis and representative molecules(CK20 and CDX2)expression indicated that there is high similarity between colorectal cancer organoids and patient tumors.In the in vitro expanded and cultured TILs,colorectal cancer-reactive T cells with upregulated CD137 expression and increased IFN-γ secretion were screened out successfully,among which TCR2-T cells demonstrated superior tumor reactivity and in vitro tumor killing function.In conclusion,a platform for screening and function validation of reactive TCRs based on CRC-Org has been established,providing a technological platform for the translational application of individualized T-cell therapy for colorectal cancer.

Objective To measure and compare the cerebral blood flow(CBF)of children with autism spectrum disorder(ASD),global developmental delay(GDD),and ASD with GDD groups via arterial spin labeling(ASL)technique,and to evaluate the diag-nostic value of CBF values.Methods ASL images of ASD,GDD,and ASD with GDD groups of children were firstly acquired,and the CBF values of frontal lobe,temporal lobe,parietal lobe,occipital lobe,striatum and thalamus region of interest(ROI)were fur-ther measured,respectively.One-way analysis of variance or Kruskal-Wallis H test was used to compare the differences in CBF values among these three groups,and the receiver operating characteristic(ROC)curve was used to analyze the efficacy of CBF values in distinguishing ASD with GDD from without GDD.Results ASD with GDD had significantly lower CBF values in the left and right frontal lobes than those with ASD or GDD alone,and the differences were statistically significant(P<0.05).The CBF values in the left and right frontal lobes effectively distinguished ASD with GDD from without GDD[area under the curve(AUC)>0.7].Conclusion ASL technique can noninvasively assess CBF in children with or without GDD,helping to understand the pathophysiology of ASD with GDD and improving diagnostic accuracy.

Objective:To explore chromosomal copy number variations (CNVs) and pregnancy outcomes in fetuses with mild to moderate isolated ventriculomegaly (IVM), but without other indications for invasive prenatal diagnosis.Methods:A retrospective analysis was conducted on clinical data of 215 singleton pregnancies with mild to moderate IVM (lateral ventricular width≥10-<15 mm) who underwent chromosomal microarray analysis (CMA), not indicated by advanced age, high risk in serum screening or abnormal history of pregnancy, at the Fujian Maternity and Child Health Hospital between June 2016 and March 2023. The 215 fetuses were grouped into mild ( n=167) and moderate ( n=48) IVM;unilateral ( n=142) and bilateral ( n=73) IVM; first diagnosis of IVM before 28 weeks ( n=138) and thereafter ( n=77). Anomalies other than IVM were excluded via three-dimensional color Doppler ultrasound examination between 22 and 26 weeks of gestation. Out of these cases, 129 were confirmed by fetal cranial MRI, 191 underwent chromosomal karyotype analysis, and 202 cases received cytomegalovirus DNA quantification test for amniotic fluid. The detection rates of pathogenic CNVs in various groups were compared using Fisher's exact test. Results:Among the 215 fetuses, 11 cases (5.1%) of chromosomal abnormalities were detected through CMA, including one trisomy 21, five pathogenic CNVs, and five CNVs of uncertain clinical significance. Within the pathogenic CNVs, there were two de novo mutations with 16p11.2 microdeletion and one de novo mutation with 16p11.2 microduplication, while one 16p11.2 microduplication and one Xp22.31 microdeletion were inherited maternally. Of the CNVs of uncertain significance, there were two 16p13.11 microduplications, each inherited from a different parent, one paternally and one maternally; meanwhile, family validation was refused in the other three cases with 3p22.1 microdeletion, 3p26.3 microdeletion, and 9q21.33q22.31 microduplication. The detection rate of pathogenic CNVs in the moderate IVM group was higher than that in the mild IVM group [6.3% (3/48) vs. 1.2% (2/167)], but the difference was not statistically significant ( P=0.083). Similarly, no significant difference was found in the detection rate of pathogenic CNVs when comparing the unilateral IVM group [2.1% (3/142)] with the bilateral IVM group [2.7% (2/73)], nor between the group diagnosed with VM before 28 weeks gestation [2.2% (3/138)] and that diagnosed ≥28 weeks [2.6% (2/77)] (both P>0.05). After the exclusion of fetuses with chromosomal pathogenic abnormalities ( n=11), cytomegalovirus infection( n=1), and additional ultrasound anomalies ( n=7), and several cases with missing data intrauterine outcomes were followed up in 169 IVM fetuses, including 104 (61.5%) improved, 60 (35.5%) unchanged, and five (3.0%) progressed. Follow-ups were successful for 194 women, of which eight pregnancies were terminated (including one trisomy 21, four pathogenic CNVs, one fetal cytomegalovirus infection, and two progressed to severe IVM). Among the 186 newborns, one was diagnosed with X-linked ichthyosis, and one child who progressed to severe IVM before born was followed until 20 months of age without notable phenotypic abnormalities. The rest 184 babies, including those with CNVs of uncertain clinical significance, exhibited no developmental abnormalities during follow-up between the ages of three months and six years. Conclusions:For those fetuses with isolated mild to moderate IVM, but without indications for prenatal diagnosis such as advanced maternal age, high risk in serum screening or abnormal history of pregnancy, remain having the risk for chromosomal aberrations, and 16p11.2 microdeletion/microduplication might be a frequent CNV associated with this condition. Aside from those with pathogenic chromosomal aberrations, fetal cytomegalovirus infection, or progressive enlargement of the lateral ventricles, most fetuses with isolated mild to moderate IVM have a good prognosis.

Objective:To investigate the clinical value of isolated fetal echogenic bowel (FEB) as an indicator for invasive prenatal diagnosis.Methods:This retrospective study enrolled 183 pregnant women who were diagnosed with isolated FEB and underwent invasive prenatal diagnosis in Fujian Maternity and Child Health Hospital from August 2013 to January 2021. Clinical data including the results of conventional karyotyping and chromosomal microarray analysis (CMA), cytomegalovirus (CMV) DNA loads in amniotic fluid and pregnancy outcomes were reviewed analyzed. Chi-square test was used for statistical analysis Results:Karyotyping was performed on all of the 183 fetuses and three (1.64%) aneuploidies (one case of trisomy 21, one trisomy 18 and one 47,XYY syndrome) were detected. One trisomy 21 and four pathogenic (P)/likely pathogenic (LP) copy number variation (CNV) were detected among 108 fetuses who received CMA. The detection rate of P/LP chromosomal abnormalities by CMA was higher than that by karyotyping, but there was no significant difference between them [4.63% (5/108) vs 0.93% (1/108), χ 2=1.54, P>0.05]. In addition, three cases of variants of uncertain significance (VOUS) were detected by CMA. CMV DNA loads of fetal cells in the amniotic fluid samples of the 166 cases were determined, and only one (0.6%) was positive (CMV DNA up to 7.01×10 6 copies/ml), and no abnormalities were found in karyotype analysis and CMA detection. A total of 176 cases were followed up, and among them only one case of intrauterine infection and seven cases (three aneuploidies and four P/LP CNV) of chromosomal abnormalities were terminated after genetic counseling. Three fetuses with VOUS and other 165 fetuses without chromosomal abnormalities had a good prognosis after birth. Conclusions:Isolated FEB may be the abnormal ultrasound finding in fetuses with chromosomal abnormalities or CMV infection. Prenatal genetic testing and the exclusion of intrauterine infection are important for management during pregnancy and prognosis assessment of FEB.

Objective:To conduct a Meta-analysis on the application effect of information management on safe in-hospital transfer of patients in China.Methods:Using computers to search for randomized controlled trials and quasi experimental studies on the effect of information management on safe in-hospital transfer of patients in China from China National Knowledge Infrastructure, VIP, Wanfang Database, China Biomedical Mediline disc, PubMed, Embase, Web of Science, CINAHL and Cochrane Library. The search period was from establishment of databases to May 17, 2022. Literature screening, quality evaluation and data extraction were conducted independently by two trained researchers. Stata 15.1 software was used for Meta-analysis.Results:A total of 14 articles were included, involving a total of 130 670 patients. The results of Meta-analysis showed that the incidence of adverse event in in-hospital transfer of patients in the information management group was shorter than that in the control group ( OR=0.24, 95% CI: 0.17-0.35, P<0.01), duration of in-hospital tranfer was longer than that in the control group ( WMD=-5.76, 95% CI: -8.30-3.22, P<0.01), and patients' satisfaction ( OR=1.11, 95% CI: 1.05-1.17, P<0.01) and satisfaction of medical personnel responsible for transfer ( OR=1.37, 95% CI: 1.13-1.66, P<0.01) were higher than those of the control group. Conclusions:Information management can effectively control the incidence of adverse events in in-hospital transfer of patients in China, shorten the time required for hospital transfers and improve the satisfaction of patients and medical staff in hospital transfers.

This study was performed to explore the impact of glutamine(Gln)on the anti-tumor immune response of CD8+ T cells and its mechanism.TCGA database was used to analysis the relationship between tumor Gln metabolism and the quantity and functionality of infiltrating CD8+ T cells.CRISPR/Cas9 was employed to knock down GLS expression in mouse MC38 cells,and a mouse tumor model was established.Flow cytometry was conducted to assess tumor proliferation,apoptosis,and the quantity and functionality of tumor-infiltrating immune cells.Lymphocytes isolated from health individuals were treated with Gln-deficient media,complete media or media supplemented with GSH,RSL3 in vitro.Then the apoptosis,the expression levels of GPX4,Lipid-ROS,and effector function protein of CD8+ T cells were detected by flow cytometry.Furthermore,RNA-seq was performed to analyze the differential gene expression on the Gln-depleted CD8+ T cells.Data showed that tumor Gln metabolism was inversely associated with the quantity and functionality of tumor-infiltrating CD8+ T cells.Low expression of GLS in MC38 cells could inhibit C57BL/6 tumor growth,decrease Ki-67 expression,promote casepase-3 expression,increase the amount of tumor-infiltrating immune cells,suppress PD-1,TIM-3,and LAG-3 expression,and enhance CD137,CD107a,IFN-γ and TNF-α expression in tumor-infiltrating CD8+ T cells.RNA-seq results indicated an upregulation of ferroptosis genes TFRC,HMOX1,CYBB and SLC7A11 in CD8+ T cells following glutamine deficiency.Gln deficiency led to lower CD137,CD107a,IFN-γ,GSH,GPX4 expression,increased Lipid-ROS level,and caused cell death in CD8+ T cells.Supplementation of GSH upregulated GPX4 expression,downregulated Lipid-ROS level,and increased IFN-γ secretion in CD8+ T cells.In conclusion,Gln deficiency inhibits the effector function of CD8+ T cells by inducing ferroptosis,and promotes tumor growth.

Objective:To explore the effect of visual mind mapping based on Mini-CEX evaluation combined with case-based learning (CBL) on improving the learning ability and teaching satisfaction of nursing students in department of general surgery.Methods:A total of 120 nurses rotating in the Department of General Surgery, Panzhihua Central Hospital (Clinical Medical College of Panzhihua University) from September 2019 to July 2020 were selected as research objects, and randomly divided into a control group and a study group, with 60 nurses in each group. The control group used traditional teaching, and the study group used visual mind mapping based on Mini-CEX evaluation combined with CBL. After the training, the clinical comprehensive ability of the nurses was evaluated by theoretical and practical assessment, and the self-learning ability and teaching satisfaction of the nurses were analyzed through self-made questionnaire survey. SPSS 22.0 was used for t test and chi-square test. Results:The theoretical and practical assessment scores of nursing students in the study group were significantly higher than those in the control group[(95.01±3.52) vs. (83.26±4.05); (96.14±3.22) vs. (81.17±4.30)] ( P=0.001). Before the rotation training, there was no statistical difference between the study group and the control group in the scores of self-motivation beliefs, task analysis, self-monitoring and adjustment, and self-evaluation ( P>0.05). After the rotation training, the scores of above 4 aspects were significantly higher in study group than the control group ( P<0.05). The nurse trainees in the study group were significantly superior to those in control group in the following 7 aspects: reasonable arrangement of the teaching plan, novelty of the teaching mode, improvement of clinical nursing skills, improvement of the nurse-patient communication ability, improvement of the emergency response ability, and overall teaching satisfaction ( P=0.001). Conclusion:Visual mind mapping based on Mini-CEX evaluation combined with CBL applied to clinical teaching training of nursing students in the department of general surgery can effectively improve the effectiveness of nursing teaching and teaching satisfaction, improve the learning ability of nurses, and improve the nursing level of nursing students in the department of general surgery.

Anaphylaxis is increasingly in children, which is currently undernotified, underdiagnosed, and undertreated in China.In order to further improved the understanding and management of anaphylaxis, this issue reviews the pathogenesis, triggers and risk factors, clinical diagnosis and management of anaphylaxis, thus offers the recommedations of anaphylaxis in Chinese children based on previous published evidence-based guidelines and practice parameters.Recommendation aims to develop guiding principles for the diagnosis and management of anaphylaxis in children, and provide a framework for the development of new guidelines.

[Abstract] Objective: To investigate the effects of exosome originated from bone marrow mesenchymal stem cell (BMSCs) on proliferation, migration and invasion of prostate cancer PC-3 cell and its mechanism. Methods: qPCR was used to detect the expression level of miR-21-5p in prostate cancer cell lines. The morphology of exosomes isolated from BMSCs was observed with an electron microscope. Western blotting was used to detect the expressions of exosome surface markers and the epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Vimentin). Dual luciferase reporter gene experiment was used to detect the targeted regulation relationship between miR-21-5p and PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2). PC-3 cells were co-cultured with 10 μl BMSCs exosomes suspension (Exo group), transfected with sh-PHLPP2 or antagomiR, then CCK-8 and Transwell experiments were used to detect changesinproliferation,migrationandinvasionofPC-3cell.Results: miR-21-5p was highly expressed in prostate cancer PC-3 cell line. The exosomes in the supernatant of BMSCs culture fluid were successfully isolated, and the typical vesicle-like structures of exosomes were observed under transmission electron microscope. Exosomes expressed specific proteins such as CD9, CD63 and CD81. In the Exo group, the proliferation, invasion, migration, as well as the expressions of N-cadherin, Vimentin and miR-21-5p in PC-3 cells were significantly higher than those in the control group (all P<0.05). PHLPP2 is a target gene of miR-21-5p. Compared with the control group, the expression of PHLPP2 in PC-3 cells of Exo group and sh-PHLPP2 group was significantly reduced (0.66±0.09, 0.42±0.05 vs 1.09±0.08, all P<0.01); cell viability, invasion and migration were significantly improved (all P<0.01); and E-cadherin expression level was significantly reduced while N-cadherin and Vimentin expressions were significantly increased (both P<0.05). Conclusion: miR-21-5p is highly expressed in prostate cancer PC-3 cell line. BMSC exosome miR-21-5p can increase the proliferation, migration and invasion ability of PC-3 cells through targeted down-regulation of PHLPP2.