Palmitoylation of KSHV pORF55 is required for Golgi localization and efficient progeny virion production.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus etiologically associated with multiple malignancies. Both latency and sporadic lytic reactivation contribute to KSHV-associated malignancies, however, the specific roles of many KSHV lytic gene products in KSHV replication remain elusive. In this study, we report that ablation of ORF55, a late gene encoding a tegument protein, does not impact KSHV lytic reactivation but significantly reduces the production of progeny virions. We found that cysteine 10 and 11 (C10 and C11) of pORF55 are palmitoylated, and the palmytoilation is essential for its Golgi localization and secondary envelope formation. Palmitoylation-defective pORF55 mutants are unstable and undergo proteasomal degradation. Notably, introduction of a putative Golgi localization sequence to these palmitoylation-defective pORF55 mutants restores Golgi localization and fully reinstates KSHV progeny virion production. Together, our study provides new insight into the critical role of pORF55 palmitoylation in KSHV progeny virion production and offers potential therapeutic targets for the treatment of related malignancies.

Assessment of Cerebral White Matter Involvement in Amyotrophic Lateral Sclerosis Patients With Disease Progression and Cognitive Impairment by Fixel-Based Analysis and Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Previous studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses. PURPOSE: To detect WM microstructural changes in ALS patients using fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI. STUDY TYPE: Prospective. POPULATION: Thirty-six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years). FIELD STRENGTH/SEQUENCE: 3 T; NODDI and FBA (b-values = 0, 1000, and 2500 seconds/mm2 ). ASSESSMENT: Subgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS-ci/ALS-nci). Fiber density (FD), fiber-bundle cross-section (FC), combined fiber density and cross-section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined. STATISTICAL TESTING: Chi-square test, Mann-Whitney U test, two-sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P-value <0.05 was considered significant. RESULTS: ALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS-ci than ALS-nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = -0.408). DATA CONCLUSION: FBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression.

The Use of Diffusion Tensor Imaging in the Identification of Acute Rejection and Chronic Allograft Nephropathy After Renal Transplantation.

BACKGROUND: Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. PURPOSE: To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). STUDY TYPE: Prospective. SUBJECTS: Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). FIELD STRENGTH/SEQUENCE: 1.5 T/T2-weighted imaging and DTI. ASSESSMENT: The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. STATISTICAL TEST: One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. RESULTS: The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 µmol/L vs. 82.3 ± 20.9 µmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DATA CONCLUSION: DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

A non-metallic SERS-based immunoassay founded by light-harvesting effect and strengthened chemical enhancement.

Owing to its promising biocompatibility and reliable sensitivity, semiconductor-guided surface-enhanced Raman scattering (SERS) technology has aroused widespread concern in clinical immunoassays. Herein, the well-improved light capture capability of MoS2 with a novel three-dimensional (3D) flower-like morphology was combined with the synergistic chemical enhancement from a MoS2@red phosphorus (RP) hybrid system, facilitating an attractive non-metallic SERS-based detection of ferritin in serum. Owing to the remarkable enhancement factors of both the immunoprobe and immunosubstrate, which were comparable to noble metal, an extremely low limit detection of 11.5 pg mL-1 was achieved in the absence of fluorescence interference. In particular, the trace ferritin in the clinical serum sample was successfully monitored, demonstrating superior sensitivity to the traditional chemiluminescent method. Overall, this study convincingly revealed the feasibility and reliability of SERS-based immunoassays induced by biocompatible semiconductors, which has opened a new way to implement the detection and tracking of biomarkers in the human body.

lncRNA SNHG11 Promotes Gastric Cancer Progression by Activating the Wnt/ß-Catenin Pathway and Oncogenic Autophagy.

Long non-coding RNAs (lncRNAs) are under active investigation in the development of cancers, including gastric cancer (GC). Oncogenic autophagy is required for cancer cell survival. The present study aimed to investigate the regulatory role of lncRNA small nucleolar host gene 11 (SNHG11) in GC. We show that SNHG11 is upregulated in GC, and that its upregulation correlated with dismal patient outcomes. Functionally, SNHG11 aggravated oncogenic autophagy to facilitate cell proliferation, stemness, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in GC. Mechanistically, SNHG11 post-transcriptionally upregulated catenin beta 1 (CTNNB1) and autophagy related 12 (ATG12) through miR-483-3p/miR-1276, while the processing of precursor (pre-)miR-483/pre-miR-1276 was hindered by SNHG11. SNHG11 induced GSK-3ß ubiquitination through interacting with Cullin 4A (CUL4A) to further activate the Wnt/ß-catenin pathway. Intriguingly, SNHG11 regulated autophagy in a manner dependent on ATG12 rather than the Wnt/ß-catenin pathway, whereas SNHG11 contributed to the malignant behaviors of GC cells via both pathways. Finally, SNHG11 upregulation in GC cells was shown to be transcriptionally induced by TCF7L2. In conclusion, we reveal that SNHG11 is an onco-lncRNA in GC and might be a promising prognostic and therapeutic target for GC.

[Efficacy Evaluation of Three Endoscopic Therapies of Isolated Gastric Varices with Modified Tissue Adhesive].

Objective: To evaluate the efficacy of three endoscopic therapies of isolated gastric varices (IGV) with modified tissue adhesive. Methods: A retrospective analysis was conducted with the clinical data of 73 IGV patients who were treated between January 2008 and December 2019 at Beijing Ditan Hospital. Patient clinical data on age, sex, etiology, biochemistry findings, Child-Pugh classification, the type of spontaneous shunt, preoperative bleeding history, and the presence or absence of liver cancer were collected. The three therapies evaluated were endoscopic intravenous injection of tissue glue combined with lauromacrogol, endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, and endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. Their respective clinical treatment outcomes, including ectopic embolism rate, survival rate, rebleeding rate, amount of lauromacrogol and tissue glue used, the number of endoscopic clips used, and the number of times of the procedure the patient underwent, were evaluated. Results: In the patient baseline data, Child-Pugh grade, preoperative thrombus formation, and the presence or absence of liver cancer, showed significant difference between the three therapies ( P<0.05). There was no significant difference in the rates of ectopic embolism among the three methods ( P>0.05), but no ectopic embolism occurred after endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, or after endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. There was no significant difference in the survival rate, the rebleeding rate, amount of lauromacrogol and tissue glue used for the three therapies, but there was significant difference in the number of endoscopic clips used and the number of times the procedure was conducted within one year ( P<0.05). Conclusion: The two endoscopic therapies of intravenous injection of modified tissue glue, one assisted by clip and the other assisted by clip and LOOP, can help reduce the number of procedures IGV patients undergo within one year.

Prognosis of endotherapy versus splenectomy and devascularization for variceal bleeding in patients with hepatitis B-related cirrhosis.

OBJECTIVE: This study aimed to compare the long-term outcome of endotherapy versus a combination of splenectomy and devascularization for variceal bleeding in patients with hepatitis B-related cirrhosis (HBRC). MATERIALS AND METHODS: A total of 1074 patients with HBRC and acute variceal bleeding (AVB) treated with endotherapy and 248 patients with HBRC treated with a combination of splenectomy and devascularization surgery were included in the analysis. After one-to-one propensity score matching, 151 paired patients were selected. The primary end-point was death. The secondary outcomes were 3-year survival, 5-year survival, and rebleeding. Complications were recorded. RESULTS: The median follow-up time was 1165 days in the endoscopic group and 1709 days in the surgical group. Before matching, the 1-year, 3-year, and 5-year survival rates were significantly lower in the endoscopic group than in the surgical group (91.1 vs 96.3%, P = 0.017; 79.6 vs 91.6%, P = 0.001; 65.2 vs 81.3%, P = 0.001). After matching, no significant differences were found between groups (94.5 vs 95.2%, P = 0.767; 87.0 vs 88.9%, P = 0.635; 77.9 vs 77.9%, P = 0.905). The rebleeding rate was lower in the surgical group than in the endoscopic group; the rebleeding-free survival rate was similar in the two groups. No patient died of complications. No statistically significant difference was observed in complications between groups. CONCLUSIONS: Both endotherapy and a combination of splenectomy and devascularization are good choices for patients with AVB. The rebleeding rate was lower after the surgical procedure, but the long-term prognosis was similar.

Influence of transition readiness from paediatric to adult health care on quality of life in child-parent dyads with long-term conditions.

AIM: To delineate the impact of perspective of children's transition readiness from paediatric to adult health care on quality of life in child-parent dyads with long-term conditions. We used Actor-Partner Interdependence Model to identify actor effects (effect of one's own transition readiness on one's own quality of life) and partner effects (effect of one's own transition readiness on the partner's quality of life). DESIGN: A multi-centre cross-sectional survey. METHODS: The study was conducted in two paediatric hospitals in China from October 2018-August 2019. We used a researcher-designed questionnaire to collect demographic and clinical characteristics. Furthermore, we used four questionnaires assessing transition readiness and quality of life in child and parent respectively to collect data from 370 child-parent dyads. Structural equation modelling was applied to estimate the effect of actor-partner interdependence models. RESULTS: The total score of transition readiness had two actor effects on total child and parent quality of life controlling for age (ßchildren  = 3.335, p = .032 and ßparents  = 8.952, p < .001), while only one actor effect controlling for gender (ßparents  = 8.891, p < .001). Specific transition readiness dimensions had different partner effects on different domains of children and parents' quality of life. Moreover, younger children and fathers had a better quality of life. CONCLUSION: Our study verified inherently interpersonal relationship that transition readiness appeared to influence quality of life in child-parent dyads with long-term conditions. IMPACT: This study was the first to verify mutual influence of transition readiness and quality of life in child-parent dyad using actor-partner interdependence model. Nurses who design the transition promoting programs should consider the effective communication between healthcare provider and child-parent dyads and support parents' involvement to improve shared understanding about managing child's condition, especially for older children and mothers.

Psychometric properties of the 'Self-Management and Transition to Adulthood with Rx = Treatment Questionnaire' in Chinese children and young people with chronic diseases.

AIMS: The aims of this work were to translate, culturally adapt and evaluate the reliability and validity of the Chinese version of the Self-Management and Transition to Adulthood with Rx = Treatment Questionnaire. BACKGROUND: Children and young people with chronic diseases are expected to start self-managing their diseases and have a smooth and coordinated transition from paediatric- to adult-oriented care. DESIGN: This study involved the cultural adaptation of a questionnaire into Chinese and examined its factor structure. METHODS: This was a multicentre cross-sectional study of children and young people/adolescents (8-18 years) who were diagnosed with chronic diseases in China from June 2016 to December 2018. Exploratory and confirmatory factor analyses were performed to analyse the questionnaire's validity. RESULTS: Four major factors were identified in the Chinese version of the questionnaire, and it had a good fit to the target population. The internal reliability was good. All factors were positively and strongly correlated with the total score. The t test revealed that the Medication Management score was not significantly different between two age groups (8-11 and 12-18 years), but the scores of the other factors and overall scale were lower in the 8-11 years age group. CONCLUSION: The Chinese version of the questionnaire has good reliability and validity in the Chinese context.

New model predicting gastroesophageal varices and variceal hemorrhage in patients with chronic liver disease.

INTRODUCTION AND OBJECTIVES: The predictors for gastroesophageal varices (GOV) and hemorrhage development have not been well studied in different liver diseases or different population. This study aimed to evaluate whether a new algorithm focusing on chronic hepatitis B (CHB) patients is also applicable to other chronic liver diseases (CLDs) in Chinese population. PATIENTS OR MATERIALS AND METHODS: We retrospectively analyzed 659 CHB patients and 386 patients with other CLDs. A total of 439 CHB patients were included in training set, the other 220 CHB patients and other patients with CLDs were included in validation set. A new algorithm for diagnosing GOV was established and its sensitivity and specificity for predicting the varices was verified. RESULTS: Multivariable logistic regression revealed that the rough surface of the liver (p<0.001), splenic thickness (p<0.001), and liver stiffness (p=0.006) were independent predictors of GOV. The new algorithm was considered to be a reliable diagnostic model to evaluate the presence of varices. The AUROC was 0.94 (p<0.001) in CHB validation set and 0.90 (<0.001) in non-CHB validation set. When the cut-off value was chosen as -1.048, the sensitivity and specificity in diagnosing GOV in CHB population were 89.1% and 82.5%, respectively. Importantly, the new algorithm accurately predicted the variceal hemorrhage not only in CHB patients, but also in patients with other CLDs. CONCLUSION: The new algorithm is regarded as a reliable model to prognosticate varices and variceal hemorrhage, and stratified not only the high-risk CHB patients, but also in patients with other CLDs for developing GOV and variceal bleeding.

Long noncoding RNA FOXD3-AS1 promotes colon adenocarcinoma progression and functions as a competing endogenous RNA to regulate SIRT1 by sponging miR-135a-5p.

More and more documents have proved that the abnormal expression of long noncoding RNAs (lncRNAs) are correlated with the initiation and progression of colorectal cancer (CRC). lncRNA FOXD3-AS1 has been reported in glioma for its oncogenic property. According to the survival analysis of The Cancer Genome Atlas database, FOXD3-AS1 upregulation implied lower survival rate of patients with CRC. Quantitative real-time polymerase chain reaction showed the overexpression of FOXD3-AS1 in both CRC tissues and cells. The Kaplan-Meier method demonstrated the prognostic value of FOXD3-AS1 for patients with CRC. To explore the effect of FOXD3-AS1 on CRC progression, loss-of-function experiments were carried out, whose results indicated that knockdown of FOXD3-AS1 suppressed cell proliferation, migration, and invasion, inhibited cell cycle and promoted cell apoptosis in vitro. In vivo experiments affirmed that FOXD3-AS1 affected tumor growth. FOXD3-AS1 expression was enriched in the cytoplasm of CRC cells. Mechanism experiments revealed that FOXD3-AS1 served as a competing endogenous RNA to upregulate SIRT1 by sponging miR-135a-5p. In addition, SIRT1 silencing also restrained cell proliferation and motility. Rescue assays revealed the biological function of FOXD3-AS1/miR-135a-5p/SIRT1 axis in CRC progression. In conclusion, FOXD3-AS1 promotes CRC progression by regulating miR-135a-5p/SIRT1 axis, shedding lights on the way to CRC treatments.

Clip-assisted endoscopic cyanoacrylate injection for gastric varices with a gastrorenal shunt: a multicenter study.

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of clip-assisted endoscopic cyanoacrylate injection for gastric varices with a gastrorenal shunt. METHODS: Records were reviewed of patients with gastric varices and concomitant gastrorenal shunts who underwent clip-assisted endoscopic cyanoacrylate injection at three tertiary centers between April 2016 and October 2018. The assessed outcomes were technical success rate, eradication of gastric varices, cyanoacrylate embolization, and all-cause rebleeding. RESULTS: A total of 61 patients were analyzed. The procedure was successful in all patients (100 %). Gastric varices were eradicated in 30 of 33 patients (90.9 %) according to contrast-enhanced computed tomography re-examination within 1 month after the procedure. No symptoms or signs of cyanoacrylate embolization related to the procedure were observed. Four patients (6.6 %) were lost to follow-up. All-cause rebleeding occurred in 13/57 patients (22.8 %) during a median follow-up period of 225 days (interquartile range 114 - 507 days). CONCLUSIONS: Clip-assisted endoscopic cyanoacrylate injection appeared to be a safe procedure that was convenient and efficacious in the treatment of gastric varices with concomitant gastrorenal shunt.

Hierarchical porous carbon sheets derived on a MgO template for high-performance supercapacitor applications.

Carbon-based supercapacitors have attracted considerable academic and practical interest due to their advantages of low cost, high power density, and superior durability. Herein, we report the facile synthesis of hierarchical porous carbon sheets (HPCSs) featuring a high specific surface area (2788 m2 g-1), derived from pyrrole through a combination of MgO template carbonization and KOH activation. The hierarchical pores with the co-existence of micropores and mesopores were obtained in the HPCSs. Benefiting from the high surface area, well-balanced pore size distribution as well as high conductivity, the prepared HPCSs exhibited a high gravimetric specific capacitance of 226.4 F g-1 at a scan rate of 1 mV s-1 in the electrolyte of 1 M H2SO4 in the two-electrode configuration. Moreover, the excellent electrochemical long-cycle stability has been demonstrated by 10 000 cycles of rapid charging-discharging at 10 A g-1 with a capacitance retention of 97.3%. The electrochemical performance clearly indicates the promising potential of using HPCSs as electrode materials for supercapacitors.

Antiviral therapy reduces rebleeding rate in patients with hepatitis B-related cirrhosis with acute variceal bleeding after endotherapy.

BACKGROUND: The preventive effects of antiviral therapy to reduce rebleeding rate in patients with hepatitis B-related cirrhosis undergoing endoscopic treatment have not yet been reported. METHODS: In this retrospective cohort study, 1139 patients with chronic hepatitis B with first acute variceal bleeding after endoscopic therapy from September 2008 to December 2017 were included. Among them, 923 who received and 216 who did not receive antiviral therapy were followed up for rebleeding. Cumulative rebleeding rate was calculated using the Kaplan-Meier method. Univariate and multivariate logistic regression analyses were performed to estimate the effects of antiviral therapy on rebleeding risk. The propensity score matched method and inverse probability of treatment weighting analysis were used to calculate the rebleeding rate between the antiviral and non-antiviral groups. RESULTS: The rebleeding rates were 40.5, 60.7, 72.6, and 89.2% in antiviral group at 1, 2, 3, and 5 years, respectively. The corresponding rebleeding rates in the non-antiviral group were 54.2, 72.4, 84.4, and 93.3%, respectively. The multivariate logistic regression analysis revealed that antiviral therapy was an independent protective factor associated with rebleeding. CONCLUSION: Antiviral treatment significantly reduced rebleeding rate in patients with HBV-related cirrhosis who received endoscopic treatment after the first variceal bleeding.

Effects of caregiver-involved interventions on the quality of life of children and adolescents with chronic conditions and their caregivers: a systematic review and meta-analysis.

PURPOSE: Childhood chronic conditions have a considerable effect on the quality of life (QoL) of pediatric patients and their caregivers. The purpose of this meta-analysis was to evaluate the effects of caregiver-involved interventions on the QoL of children and adolescents with chronic conditions and their caregivers. METHODS: The PubMed, EMBASE, Web of Science, Cumulative Index of Nursing and Allied Health Literature, Academic Search Complete, Education Resource Information Center, and PsycINFO databases were searched for published randomized controlled trials from inception to April 2016. Two reviewers (NS and JM) independently screened included studies and assessed study quality. The meta-analyses and meta-regressions using random-effects models were performed with the Comprehensive Meta-analysis software (version 3, Biostat, Englewood, NJ). RESULTS: Fifty-four studies involving 10075 pediatric patients diagnosed with asthma, diabetes, cancer, hypersensitivity, cerebral palsy, arthritis, or sickle cell diseases and 10015 caregivers were included in our analysis. The interventions mainly involved education about disease, skill training, environment change, psychological intervention, physical exercise, experience sharing, monitoring, or social support. The results demonstrated that caregiver-involved interventions significantly improved the health-related QoL (HRQoL) of caregivers [standardized mean difference (SMD) = 0.26, 95% CI 0.14-0.38, p < 0.001], particularly those delivered through the face-to-face mode (SMD = 0.32, 95% CI 0.21-0.43, p < 0.001). However, no improvements in the QoL (SMD = 0.00, 95% CI - 0.22 to 0.22, p = 1.00) and HRQoL (SMD = 0.06, 95% CI - 0.02 to 0.14, p = 0.16) of children and both caregivers and children (SMD = 0.04, 95% CI - 0.08 to 0.17, p = 0.52) were observed. CONCLUSIONS: This meta-analysis provides evidence on the positive effects of caregiver-involved interventions on the HRQoL of caregivers. Moreover, face-to-face mode is the delivery approach with a promising effect on the HRQoL of caregivers. Further research on conditions not found in this review is warranted.

Impact of Neonatal Intensive Care Unit oral feeding on neuropsychomotor outcomes at 9 months of corrected age in Chinese low-birthweight preterm infants: A retrospective study.

AIMS AND OBJECTIVES: To examine the changes in neuropsychomotor development and investigate the effect of feeding progression in Neonatal Intensive Care Unit (NICU) on neuropsychomotor outcomes in low-birthweight preterm infants within 9 months of corrected age. BACKGROUND: Low-birthweight (LBW) preterm infants (<37 weeks of gestation and birthweight <2,500 g) are at a high risk for neuropsychomotor development delay. Therefore, exploring NICU practices related to neuropsychomotor development is important. DESIGN: This is a retrospective hospital-based cohort study. METHODS: This study included 196 LBW preterm infants who were admitted to the NICU between January 2014-March 2016 and attended the follow-up growth evaluation in the clinic after discharge. The neuropsychomotor development of preterm infants was assessed every 3 months to a corrected age of 9 months using the paediatric neuropsychomotor diagnostic scale (PNDS). Generalised linear mixed models (GLMM) were performed. RESULTS: The total PNDS scores had a downward trend, but the difference on pairwise comparison was not statistically significant. In total, 18.1%, 15.2% and 9.7% of preterm infants were examined for neuropsychomotor disorders at 3, 6 and 9 months of corrected age, respectively. The result of GLMM showed that the early initiation of oral feeding with breast milk was associated with optimal neuropsychomotor development. The first 3 months of corrected age is the critical period for neurodevelopmental disorders. CONCLUSIONS: This study showed the importance of the early initiation of oral feeding with breast milk as early as possible within the NICU setting and highlighted the importance of close developmental follow-up. RELEVANCE TO CLINICAL PRACTICE: The early initiation of oral feeding with breast milk may be recommended to promote neuropsychomotor development of LBW preterm infants within the NICU setting. Early identification of neuropsychomotor developmental delays within the first 3 months may guide early interventions.

Glt25d2 Knockout Directly Increases CD25+CD69- but Decreases CD25-CD69+ Subset Proliferation and is Involved in Concanavalin-Induced Hepatitis.

BACKGROUND/AIMS: The elaborate structure of the extracellular matrix (ECM) and the appropriate surface glycoforms upon it are indispensable to CD4+ T cell regulation. METHODS: To explore the effects of Glcα1,2Galß1 glycosylation mediated by GLT25D2 (Colgalt2) for CD4+ T cell regulation, we prepared C57BL/6J Glt25d2-/- mice. In the induction of hepatitis, after concanavalin A (Con A) challenge for 6, 12, and 24 h, more extensive parenchymal injury was noted in Glt25d2-/- mice than in wild-type (WT) mice at 12 h. Immunohistochemistry and laser scanning confocal microscopy were used to detect GLT25D2 expression, and subsets of CD4+T cells was analyzed by flow cytometry. A total of 26 cytokines in serum samples were determined using Luminex technology. RESULTS: The trend in liver injury score variation was consistent with serum alanine aminotransferase and aspartate aminotransferase levels. The levels of interleukin 4 (IL-4), IL-1ß, IL-9, and several chemokines such as macrophage inflammatory protein-2, eotaxin, and growth-related oncogene α were significantly increased in Glt25d2-/- mice compared with WT mice after Con A challenge. A further phenotype analysis of primary Glt25d2-/- CD4+ T cells showed that Glt25d2 knockout increased the frequency of the CD25+CD69- subset but decreased the frequency of the CD25-CD69+ subset after Con A challenge for 6, 12, and 24 h compared with those of WT CD4+ T cells. Activation-induced apoptosis was also significantly increased in Glt25d2-/- CD4+ T cells after Con A challenge compared with WT CD4+ T cells. Lectin microarray hybridization showed that Glt25d2 knockout increased the binding activity of Narcissus pseudonarcissus lectin to CD4+ T cells but Amaranthus caudatus lectin-binding activity was lost during Con A challenge. CONCLUSION: The present results suggest that collagen glycosylation mediated by GLT25D2 may regulate a subset of CD4+ T cells and be involved in the pathogenesis of Con A-induced hepatitis.

Dihydromyricetin inhibits caerulin-induced TRAF3-p38 signaling activation and acute pancreatitis response.

Acute pancreatitis (AP) is a common inflammatory disease in gastrointestinal tract. Our previous study has shown that caerulin induces TNF receptor-associated factor 3 (TRAF3)-p38 signaling activation and pro-inflammatory response in macrophages, causing damage to co-cultured pancreatic acinar cells. Dihydromyricetin (DHM) is a flavonoid extracted from Ampelopsis grossedentata, which has displayed anti-inflammation and anti-oxidant functions. Our results here show that DHM potently inhibited caerulin-induced expression and productions of multiple pro-inflammatory cytokines (IL-1ß, TNF-α and IL-17) in murine bone marrow-derived macrophages (BMDMs). DHM significantly inhibited caerulin-induced TRAF3 protein stabilization, TRAF3-mitogen-activated protein kinase kinase 3 (MKK3) association and following MKK3-p38 activation in BMDMs. Significantly, DHM was ineffective against caerulin in TRAF3-silenced BMDMs. Importantly, DHM supplement attenuated the cytotoxicity of caerulin-activated BMDMs to co-cultured pancreatic acinar cells, resulting in significantly decreased acinar cell death and apoptosis. In vivo, DHM co-administration largely attenuated pancreatic and systemic inflammation in caerulin-injected AP mice. Together, DHM inhibits caerulin-induced TRAF3-p38 signaling activation and AP response. DHM could be further studied as a potential anti-AP agent.

[Impact of transition readiness on quality of life in children with chronic diseases].

OBJECTIVE: To investigate the current quality of life in children with chronic diseases, and to explore the impact of transition readiness on quality of life. METHODS: A total of 332 children with chronic diseases from two children's hospitals in Shanghai, China were enrolled. A self-designed demographic questionnaire, Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQLTM 4.0), and Self-Management and Transition to Adulthood with Rx=Treatment (STARx) Questionnaire were used to evaluate transition readiness and quality of life. RESULTS: The children with chronic diseases had a significantly lower total quality of life score than the national norm (74.66±15.85 vs 81.81±12.03; P<0.001). Doctor-patient communication and health care responsibilities (the child's abilities to take care of himself/herself and adaptation to the process of diagnosis and treatment from childhood to adulthood) were positively correlated with the scores on each dimension of quality of life (P<0.05). Duration of disease, time of absence from school within six months, and the number of types of drugs taken orally were negatively correlated with the total quality of life score (rs=-0.172, -0.236, and -0.280; P<0.05). The residence (urban or rural area), monthly family income, parents' educational level, and father's occupation had significant influence on children's quality of life (P<0.05). The hierarchical multiple regression analysis revealed that doctor-patient communication and health care responsibilities led to a 14.3% increase in the explanation of the total variation in quality of life (P<0.001). CONCLUSIONS: Quality of life is not satisfactory in children with chronic diseases. Two domains of transition readiness, namely the abilities to communicate with health providers and health care responsibilities, are major factors influencing quality of life in these children.

Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis.

The current study focused on the role of Ku70, a DNA-dependent protein kinase (DNA-PK) complex protein, in pancreatic cancer cell resistance to gemcitabine. In both established cell lines (Mia-PaCa-2 and PANC-1) and primary human pancreatic cancer cells, shRNA/siRNA-mediated knockdown of Ku70 significantly sensitized gemcitabine-induced cell death and proliferation inhibition. Meanwhile, gemcitabine-induced DNA damage and subsequent pancreatic cancer cell apoptosis were also potentiated with Ku70 knockdown. On the other hand, exogenous overexpression of Ku70 in Mia-PaCa-2 cells suppressed gemcitabine-induced DNA damage and subsequent cell apoptosis. In a severe combined immune deficient (SCID) mice Mia-PaCa-2 xenograft model, gemcitabine-induced anti-tumor activity was remarkably pontificated when combined with Ku70 shRNA knockdown in the xenografts. The results of this preclinical study imply that Ku70 might be a primary resistance factor of gemcitabine, and Ku70 silence could significantly chemo-sensitize gemcitabine in pancreatic cancer cells.