Acute kidney injury in children with lymphoma.

OBJECTIVE: To analyze the epidemiology of acute kidney injury (AKI) in children with lymphoma and to assess the incidence, risk profile of AKI, and effects on renal function in children with lymphoma during their first 30 days of hospitalization. MATERIALS AND METHODS: This was a retrospective screen of electronic hospital and laboratory databases to select hospitalized children who were first diagnosed and treated for lymphoma at Beijing Children's Hospital between 2020 and 2021. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. We analyzed the incidence and risk factors for AKI in children with lymphoma during their first 30 days of hospitalization. We also analyzed mortality rate and the incidence of kidney recovery over a 1-year follow-up period. RESULTS: Of the 295 children with lymphoma (which were all non-Hodgkin lymphoma), 42 (16.5%) experienced AKI events during the first their 30 days of hospitalization. The proportion of patients with lymphoma clinical stage 4 was higher in the AKI group than in the non-AKI group (66.7 vs. 43.7%, p < 0.05). Tumor lysis syndrome (TLS), lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma. Severe AKI was associated with TLS, sepsis, and a higher need for intensive care. Over 1-year of follow-up, none of the survivors developed impaired renal function or proteinuria. However, the mortality of children in the AKI group was significantly higher than that in the non-AKI group (p < 0.05). CONCLUSION: TLS, lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma during the first 30 days of hospitalization. Clinicians should increase their awareness of AKI in hospitalized patients with lymphoma.

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis: a nationwide retrospective study in China.

BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).

Clinical relevance of glomerular C4d deposition in children with early IgA nephropathy or Henoch-Schönlein purpura nephropathy.

BACKGROUND: Both IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephropathy (HSPN) are characterized by glomerular mesangial IgA deposition. Several large studies on adults have suggested that glomerular C4d deposition has prognostic value in IgAN. However, there are few relevant studies on the clinical value of C4d deposition in children with IgAN or HSPN. METHODS: We performed a retrospective cohort study in pediatric patients with IgAN or HSPN. Clinicopathological data were collected at the time of kidney biopsy. Kidney C4d deposition was analyzed by immunohistochemistry. The end point was defined as a ≥ 20% decrease in estimated glomerular filtration from baseline. RESULTS: We enrolled 75 children, including 36 children with IgAN and 39 with HSPN. The prevalence of C4d deposition was 36% (27/75). C4d deposition was more abundant in children with proteinuria ≥ 50 mg/kg/day (51.9% versus 20.8%, P = 0.006) or nephrotic syndrome (37.0% versus 10.4%, P = 0.006). Mesangial hypercellularity (hazard ratio [HR], 5.745, 95% confidence interval [CI], 1.670-19.761, P = 0.006) and IgM deposition (HR, 4.522, 95% CI, 1.321-15.478, P = 0.016) were associated with C4d deposition. After a median follow-up of 22 months, seven (19.4%) IgAN patients and one (2.6%) HSPN patient had decreased kidney function. In children with IgAN, positive C4d was associated with decreased kidney function (P = 0.047). CONCLUSION: Glomerular C4d deposition was associated with mesangial hypercellularity and glomerular IgM deposition in IgAN and HSPN. Glomerular C4d deposition may be a risk factor for eGFR decline in children with IgAN. A higher resolution version of the Graphical abstract is available as Supplementary information.

Contrast-enhanced ultrasonography for assessing histopathology in pediatric immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis.

BACKGROUND: Glomerular disease, including immunoglobulin A nephropathy (IgAN) and Henoch-Schönlein purpura nephritis, is one of the most common kidney diseases in children. The diagnosis of these diseases depends on pathological biopsy, although this procedure is seriously limited by its invasive and high-risk nature. OBJECTIVE: To investigate the potential of contrast-enhanced ultrasonography (CEUS) for evaluating the histopathological severity of IgAN and Henoch-Schönlein purpura nephritis (HSPN). MATERIALS AND METHODS: We investigated a total of 13 children with IgAN and 12 children with HSPN confirmed by renal histopathology. We reevaluated the pathological lesions of the children according to the Oxford classification and the Lee grading system and then all the children underwent CEUS. Using SonoLiver software, we constructed time-intensity curves of CEUS for regions of interest in the renal cortex. We analyzed CEUS quantitative parameters for IgAN and HSPN and used Spearman correlation analysis to examine the correlation between CEUS parameters and clinicopathological indexes in the study cohort. RESULTS: The CEUS parameters rise time (RT) and time to peak (TTP) were significantly higher in children with Lee grade IV than in those with Lee grades II or III. Spearman correlation analysis revealed a positive correlation between rise time and time to peak with Lee grade in the overall cohort of children, and a positive correlation between rise time and time to peak and severity of crescents in the Oxford classification scoring system. CONCLUSION: Contrast-enhanced US may be used as a noninvasive imaging technique to evaluate the severity of renal pathology and formation of crescents in children with IgAN and HSPN.

Mesangial C3 deposition and serum C3 levels predict renal outcome in IgA nephropathy.

BACKGROUND: Complement activation plays an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed to evaluate the relationship between mesangial C3 deposition and histologic lesions and to investigate the role of mesangial C3 deposition and serum C3 reduction in predicting renal outcome in IgAN children. METHODS: We performed a retrospective cohort study in children with biopsy-proven IgAN. Mesangial C3 deposition (< 2+ vs. ≥ 2+) was detected by the immunofluorescence. Histopathologic kidney grades were determined by the Oxford classification. A decreased serum C3 concentration (hypoC3) was defined when C3 < 90 mg/dl. The endpoint was composite kidney outcome with either a 30% decline in glomerular filtration rates from baseline or kidney failure during the follow-up period. RESULTS: A total of 98 children were analyzed. Mesangial hypercellularity (M) was an independent factor associated with mesangial C3 deposition (HR 3.267; 95% CI 1.028-10.389; P = 0.045). After a median follow-up period of 25 months (interquartile range 18-36 months), 6 (6.1%) children reached the endpoint. Compared with other children, a significantly higher proportion of children with composite kidney outcomes had mesangial C3 deposition ≥ 2+ and hypoC3 (3.4% versus 27.3%, P = 0.002). After adjustment for clinicopathologic risk factors, mesangial C3 deposition ≥ 2+ and hypoC3 were associated with renal outcome (HR 9.772; 95% CI 1.264-75.518; P = 0.029). CONCLUSION: Mesangial C3 deposition was associated with M in IgAN. Mesangial C3 deposition and hypoC3 were risk factors for renal outcome in children with IgAN.

Long non-coding RNA DUXAP8 promotes the cell proliferation, migration, and invasion of papillary thyroid carcinoma via miR-223-3p mediated regulation of CXCR4.

Papillary thyroid carcinoma (PTC) is a differentiated type of thyroid malignancy with a high incidence. Long non-coding RNA (lncRNA) DUXAP8 has been reported to participate in the proliferation, migration, and invasion of several cancer types. However, its association with PTC has not yet been reported. The current study aimed to investigate the role of DUXAP8 in PTC and revealed the underlying mechanisms. The expression of DUXAP8 was knocked down in two PTC cell lines and the effects of DUXAP8 on the PTC biological behavior were examined by cell counting kit-8 (CCK-8), wound healing, and transwell invasion assays. Luciferase reporter assay was used to detect the binding activity between miR-223-3p and DUXAP8. We found that knockdown of DUXAP8 inhibited the proliferation, migration, and invasion of PTC cells. DUXAP8 could sponge miR-223-3p through the specific binding site. CXCR4 was a target of miR-223-3p. The malignant phenotypes of the PTC cells were suppressed by the over-expression of miR-223-3p. Moreover, miR-223-3p inhibition or CXCR4 over-expression partly restored the proliferation, migration, and invasion activities of DUXAP8-downregulated PTC cells. The results evidenced that DUXAP8 acted as an oncogene in PTC, these effects seemed to partly dependent on the miR-223-3p/CXCR4 axis.

BrainIAK: The Brain Imaging Analysis Kit.

Functional magnetic resonance imaging (fMRI) offers a rich source of data for studying the neural basis of cognition. Here, we describe the Brain Imaging Analysis Kit (BrainIAK), an open-source, free Python package that provides computationally optimized solutions to key problems in advanced fMRI analysis. A variety of techniques are presently included in BrainIAK: intersubject correlation (ISC) and intersubject functional connectivity (ISFC), functional alignment via the shared response model (SRM), full correlation matrix analysis (FCMA), a Bayesian version of representational similarity analysis (BRSA), event segmentation using hidden Markov models, topographic factor analysis (TFA), inverted encoding models (IEMs), an fMRI data simulator that uses noise characteristics from real data (fmrisim), and some emerging methods. These techniques have been optimized to leverage the efficiencies of high-performance compute (HPC) clusters, and the same code can be se amlessly transferred from a laptop to a cluster. For each of the aforementioned techniques, we describe the data analysis problem that the technique is meant to solve and how it solves that problem; we also include an example Jupyter notebook for each technique and an annotated bibliography of papers that have used and/or described that technique. In addition to the sections describing various analysis techniques in BrainIAK, we have included sections describing the future applications of BrainIAK to real-time fMRI, tutorials that we have developed and shared online to facilitate learning the techniques in BrainIAK, computational innovations in BrainIAK, and how to contribute to BrainIAK. We hope that this manuscript helps readers to understand how BrainIAK might be useful in their research.

Serum levels of galactose-deficient IgA1 in Chinese children with IgA nephropathy, IgA vasculitis with nephritis, and IgA vasculitis.

OBJECTIVE: IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAV-N) are related diseases. Galactose-deficient IgA1 (Gd-IgA1) plays an important role in the pathology of IgAV-N and IgAN, so we aim to compare the serum levels of Gd-IgA1 in Chinese pediatric patients with IgAN, IgAV-N, and IgAV. METHODS: We retrospectively enrolled 52 patients with IgAN, 57 patients with IgAV-N, 26 patients with IgAV, and 40 healthy children. The serum levels of Gd-IgA1 were measured at the time of biopsy using a lectin-based ELISA method. RESULTS: Gd-IgA1 levels in IgAV-N patients and IgAN patients were higher than in healthy controls (303.94 ± 39.37 U/ml, 314.91 ± 47.79 U/ml vs. 273.57 ± 48.29 U/ml, P < 0.001), and Gd-IgA1 levels in IgAV-N patients were higher than in IgAV patients (303.94 ± 39/ml vs. 286. 21 ± 38.81 U/ml, P = 0.059), but the latter result is not statistically significant. The Gd-IgA1 levels in IgAV patients were comparable with those in healthy controls (286.21 ± 38.81 U/ml vs. 273.57 ± 48.29 U/ml, P = 0.267). Among the four groups, we did not observe significant correlations of Gd-IgA1 levels with eGFR, proteinuria, or the MEST-C score. CONCLUSION: Serum Gd-IgA1 maybe involved in the pathogenesis of the IgAV-N and IgAN. However, we found no statistically significant correlation between Gd-IgA1 levels and clinical and pathological features.

Upregulation of TRIAP1 by the lncRNA MFI2-AS1/miR-125a-5p Axis Promotes Thyroid Cancer Tumorigenesis.

BACKGROUND: Thyroid cancer is a very common endocrine cancer worldwide. How long noncoding RNA (lncRNA) regulates thyroid cancer is elusive. LncRNA MFI2-AS1 has been demonstrated to initiate colorectal cancer. Nevertheless, the role of MFI2-AS1 in thyroid cancer remains unknown. This study aims to determine the roles of MFI2-AS1 in thyroid cancer. METHODS: qRT-PCR was used to determine the expression of MFI2-AS1 in thyroid cancer tissues and cells. Proliferation was determined by using CCK8 and colony formation assays. Transwell assay was utilized to analyze migration and invasion. Luciferase reporter assay was performed to confirm the interaction between MFI2-AS1 and miR-125a-5p. RESULTS: MFI2-AS1 was shown to be highly expressed in thyroid cancer tissues and predicted poor prognosis. Knockdown of MFI2-AS1 inhibited proliferation, colony formation, migration and invasion of thyroid cancer cells in vitro. Bioinformatics screening identified MFI2-AS1 as the sponge for miR-125a-5p. And miR-125a-5p was further confirmed to target TRIAP1 directly. Our data further demonstrated that MFI2-AS1 promoted TRIAP1 expression via repressing miR-125a-5p. Finally, TRIAP1 was found to be upregulated in thyroid cancer tissues and its restoration reversed the effects of MFI2-AS1 depletion. CONCLUSION: Our results elucidated a novel mechanism that MFI2-AS1 promotes thyroid cancer progression via the miR-125a-5p/TRIAP1 pathway.

NIR triggered PLGA coated Au-TiO2 core loaded CPT-11 nanoparticles for human papillary thyroid carcinoma therapy.

MDR (multi-drug resistance) is one of the significant deterrents of effective chemotherapy for malignant growth. One of the powerful ways to deal with defeat of the MDR is to utilize inorganic nanoparticle-intervened tranquilize conveyance to build the medication aggregations in cancerous growth cells. In this work, we have developed the presentation that is accurately made of medication conveyance framework dependent on the TiO2 nanoparticles stacked CPT-11 to defeat the thyroid malignancy cells. The synthesized nanoparticles are characterized by spectroscopy methods (UV-vis, XPS, SEM, TEM, and DLS). The TEM results suggested that the shape of PLGA-Au-TiO2@CPT-11 of nanoparticles is ∼250 nm. After successful synthesis, we have evaluated the MTT of PLGA-Au-TiO2@CPT-11 nanoparticles with and without NIR radiations. Further, the morphological changes were observed using various biochemical stainings, such as acridine orange and ethidium bromide (AO-EB) and nuclear staining through Hoechst-33258. Also, migration and cell invasion were examined. The results show that these PLGA-Au-TiO2@CPT-11 and PLGA-Au-TiO2@CPT-11 + NIR nanoparticles exhibited promising antimetastatic property and reduced the cell invasion activity in B-CPAP and FTC-133 thyroid cancer cell lines. Based on the above findings, these PLGA-Au-TiO2@CPT-11 and PLGA-Au-TiO2@CPT-11 + NIR nanoparticles can be used as a promising candidate for the malignant thyroid cells.

Incorporating structured assumptions with probabilistic graphical models in fMRI data analysis.

With the wide adoption of functional magnetic resonance imaging (fMRI) by cognitive neuroscience researchers, large volumes of brain imaging data have been accumulated in recent years. Aggregating these data to derive scientific insights often faces the challenge that fMRI data are high-dimensional, heterogeneous across people, and noisy. These challenges demand the development of computational tools that are tailored both for the neuroscience questions and for the properties of the data. We review a few recently developed algorithms in various domains of fMRI research: fMRI in naturalistic tasks, analyzing full-brain functional connectivity, pattern classification, inferring representational similarity and modeling structured residuals. These algorithms all tackle the challenges in fMRI similarly: they start by making clear statements of assumptions about neural data and existing domain knowledge, incorporate those assumptions and domain knowledge into probabilistic graphical models, and use those models to estimate properties of interest or latent structures in the data. Such approaches can avoid erroneous findings, reduce the impact of noise, better utilize known properties of the data, and better aggregate data across groups of subjects. With these successful cases, we advocate wider adoption of explicit model construction in cognitive neuroscience. Although we focus on fMRI, the principle illustrated here is generally applicable to brain data of other modalities.

MicroRNA-205 targets HER3 and suppresses the growth, chemosensitivity and metastasis of human nasopharyngeal carcinoma cells.

PURPOSE: Nasopharyngeal carcinoma is one of the lethal cancers prevalent in Southeast Asia and Southern China. The frequent relapses, development of drug resistance, the adverse effects of chemotherapy and lack of therapeutic targets form the major hurdles in nasopharyngeal carcinoma treatment. This study was undertaken to investigate the role and therapeutic potential of miR-205 in human nasopharyngeal carcinoma cells. METHODS: Expression analysis was performed by qRT-PCR. The WST-1 and colony formation assays were used for the assessment of the cell viability. Autophagy was detected by electron microscopy and apoptosis was detected by DAPI staining. Protein expression was determined by western blot analysis. RESULTS: The expression of miR-205 was significantly downregulated in human nasopharyngeal carcinoma cells. Overexpression of miR-205 caused significant inhibition in the proliferation of CNE1 nasopharyngeal carcinoma cells. The miR-205-triggered growth inhibition was found to be mainly due to the induction of autophagy which was associated with increase in LC3B II and decrease in p62 expression. The miR-205 overexpression also caused apoptotic cell death of CNE1 cells which was concomitant with increase in the Bax/Bcl-2 ratio. Additionally, miR-205 enhanced the chemosensitivity of the nasopharyngeal carcinoma cells to cisplatin and suppressed their migration and invasiveness. In silico analysis showed that miR-205 exerts its effects by inhibiting human epidermal growth factor receptor 3 (HER3). The expression of HER3 was found to be significantly upregulated in nasopharyngeal carcinoma cells and overexpression of HER3 could nullify the effects of miR-205 on the proliferation of nasopharyngeal carcinoma cells. CONCLUSION: miR-205 may exhibit therapeutic implications in the treatment of nasopharyngeal carcinoma.

BrainIAK tutorials: User-friendly learning materials for advanced fMRI analysis.

Advanced brain imaging analysis methods, including multivariate pattern analysis (MVPA), functional connectivity, and functional alignment, have become powerful tools in cognitive neuroscience over the past decade. These tools are implemented in custom code and separate packages, often requiring different software and language proficiencies. Although usable by expert researchers, novice users face a steep learning curve. These difficulties stem from the use of new programming languages (e.g., Python), learning how to apply machine-learning methods to high-dimensional fMRI data, and minimal documentation and training materials. Furthermore, most standard fMRI analysis packages (e.g., AFNI, FSL, SPM) focus on preprocessing and univariate analyses, leaving a gap in how to integrate with advanced tools. To address these needs, we developed BrainIAK (brainiak.org), an open-source Python software package that seamlessly integrates several cutting-edge, computationally efficient techniques with other Python packages (e.g., Nilearn, Scikit-learn) for file handling, visualization, and machine learning. To disseminate these powerful tools, we developed user-friendly tutorials (in Jupyter format; https://brainiak.org/tutorials/) for learning BrainIAK and advanced fMRI analysis in Python more generally. These materials cover techniques including: MVPA (pattern classification and representational similarity analysis); parallelized searchlight analysis; background connectivity; full correlation matrix analysis; inter-subject correlation; inter-subject functional connectivity; shared response modeling; event segmentation using hidden Markov models; and real-time fMRI. For long-running jobs or large memory needs we provide detailed guidance on high-performance computing clusters. These notebooks were successfully tested at multiple sites, including as problem sets for courses at Yale and Princeton universities and at various workshops and hackathons. These materials are freely shared, with the hope that they become part of a pool of open-source software and educational materials for large-scale, reproducible fMRI analysis and accelerated discovery.

A clinicopathological comparison between IgA nephropathy and Henoch-Schönlein purpura nephritis in children: use of the Oxford classification.

BACKGROUND: There is controversy over whether IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) are the same diseases. This study focuses on the clinicopathological comparison between HSPN and IgAN in children. METHODS: Children with IgAN and HSPN who had a diagnostic renal biopsy were enrolled. This study collected the clinical data of patients at biopsy, re-evaluated the pathological lesions of patients according to the Oxford Classification (MEST-C), and made a retrospective comparison between IgAN and HSPN on different stratifications of the course (Tc) and proteinuria. RESULTS: A total of 142 children with IgAN and 57 children with HSPN were enrolled. Various stratification showed the same result, which suggested that IgAN showed more mesangial proliferation (M). HSPN showed more segmental glomerulosclerosis in the Tc > 12 m group than IgAN (S 60.0% vs. 9.10%, P = 0.008). In the non-nephrotic-range and nephrotic-range proteinuria group, there were no significant differences in MEST-C scores between IgAN and HSPN. CONCLUSION: M is more common in IgAN. HSPN had more S than IgAN over the course of more than 12 months. These results indicate the differences in the pathogenesis in IgAN and HSPN. We propose early biopsy and active treatment of HSPN within 12 months to delay the development of chronic lesions.

Novel design of NIR-triggered plasmonic nanodots capped mesoporous silica nanoparticles loaded with natural capsaicin to inhibition of metastasis of human papillary thyroid carcinoma B-CPAP cells in thyroid cancer chemo-photothermal therapy.

In the search for developing a biomedicine based nanomaterial for therapeutic applications, here we described a new benign development of Photo-triggered Gold nanodots capped mesoporous silica nanoparticles Au@MSNs loaded with capsaicin (Cap) for photothermal therapy of cancer cells. Electron microscopic techniques (SEM and TEM) studies depict the anisotropic shape of Cap-Au@MSNs with mean size ≈110 nm. The successful amine functionalization and covalent interaction of Au nanodots on the mesoporous silica surface were confirmed from the results of FTIR, XPS and UV-vis spectral analyses, which directly indicates the composition of synthesized mesoporous silica surface. Additionally, Dynamic Light Scattering (DLS) revealed that synthesized cap-AuMSNs were stable with highly negatively charged. Cap-AuMSNs exhibited extraordinary in vitro antitumor activity against the tested twp thyroid cancer cell lines (i.e., FTC-133 and B-CPAP). 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay determined that capsaicin and Cap-AuMSNs conferred strong cytotoxicity against the FTC-133 and B-CPAP cell lines. Further, evaluation of the mechanism showed that anticancer activity was achieved by inducing apoptosis in thyroid cancer cells. In addition, we found that such compounds exhibited promising antimetastatic activity and reduced the invasiveness of cancer cells. Hence, we suggesting that these Cap-Au@MSNs can be used as promising candidates for cancer therapy and deserve further investigation.

A novel CLDN16 mutation in familial hypomagnesemia with hypercalciuria and nephrocalcinosis
.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubulopathy caused by mutations in either the CLDN16 or CLDN19 genes. Two children from a consanguineous family of Chinese presented with enuresis, polyuria, polydipsia, and failure to thrive. Laboratory studies revealed hypomagnesemia, hypercalciuria, sterile leukocyturia, microscopic hematuria, and renal insufficiency. Renal ultrasound showed bilateral medullary nephrocalcinosis and urolithiasis. Gene sequencing showed compound heterozygous, missense mutations c.416C>T (p.Ala139Val) and c.320T>C (p.Leu107Pro) within CLDN16 gene in both patients, and the mutation c.320T>C (p.Leu107Pro) had never been described before. The genetic findings will expand the understanding of FHHNC.

Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR-155-5p.

PURPOSE: In the present study, we evaluated the expression and function of human long noncoding RNA (lncRNA) activated by DNA damage (NORAD) in human epithelial ovarian cancer (EOC). METHODS: NORAD expression was evaluated by qRT-PCR in EOC cell lines and in situ EOC clinical samples. Lentivirus-mediated NORAD downregulation was conducted in OVCAR-3 and ES-2 cells, and its effect on cancer cell proliferation, bufalin chemoresistance, cell-cycle transition in vitro, and xenotransplantation in vivo were examined, respectively. The likelihood of an lncRNA-microRNA (miRNA) signaling pathway was examined by probing the possible downstream competing target of NORAD, hsa-miR-155-5p. Moreover, hsa-miR-155-5p was knocked down in NORAD-downregulated EOC cells to functionally evaluate the correlation between NORAD and hsa-miR-155-5p in EOC. RESULTS: We found that NORAD was substantially upregulated in both EOC cell lines and human tumors. In OVCAR-3 and ES-2 cells, lentivirus-mediated NORAD downregulation had significant anticancer effects, as it suppressed cell proliferation, decreased bufalin chemoresistance, arrested cell-cycle transition, and inhibited xenograft growth. Also, hsa-miR-155-5p was confirmed to be the competing target of NORAD in EOC, and its knockdown in OVCAR-3 and ES-2 cells reversed the NORAD downregulation-induced anticancer functions. CONCLUSIONS: NORAD is upregulated in EOC. Inhibition of NORAD, possibly through endogenously competing against hsa-miR-155-5p, can be a new tumor-suppressing strategy in EOC.

Derivation and validation of a prediction score for acute kidney injury secondary to acute myocardial infarction in Chinese patients.

BACKGROUND: Acute kidney injury (AKI) is a major complication of acute myocardial infarction(AMI), which can significantly increase mortality. This study is to analyze the related risk factors and establish a prediction score of acute kidney injury in order to take early measurement for prevention. METHODS: The medical records of 6014 hospitalized patients with AMI in Beijing Anzhen Hospital from January 2010 to December 2016 were retrospectively analyzed. These patients were randomly assigned into two cohorts: one was for the derivation of prediction score (n = 4252) and another for validation (n = 1762). The criterion for AKI was defined as an increase in serum creatinine of ≥ 0.3 mg/dL or ≥ 50% from baseline within 48 h. On the basis of odds ratio obtained from multivariate logistic regression analysis, a prediction score of acute kidney injury after AMI was built up. RESULTS: In this prediction score, risk score 1 point included hypertension history, heart rate > 100 bpm on admission, peak serum troponin I ≥ 100 µg/L, and time from admission to coronary reperfusion > 120 min; risks score 2 points included Killip classification ≥ class 3 on admission; and maximum dosage of intravenous furosemide ≥ 60 mg/d; risks score 3 points only included shock during hospitalization. In addition, when baseline estimated glomerular filtration rate (eGFR) was less than 90 ml/min·1.73 m2, every 10 ml/min·1.73 m2 reduction of eGFR increased risk score 1 point. Youden index showed that the best cut-off value for prediction of AKI was 3 points with a sensitivity of 71.1% and specificity 74.2%. The datasets of derivation and validation both displayed adequate discrimination (an area under the ROC curve, 0.79 and 0.81, respectively) and satisfactory calibration (Hosmer-Lemeshow statistic test, P = 0.63 and P = 0.60, respectively). CONCLUSIONS: In conclusion, a prediction score for AKI secondary to AMI in Chinese patients was established, which may help to prevent AKI early.

Synergistic combination of PEGylated selenium nanoparticles and X-ray-induced radiotherapy for enhanced anticancer effect in human lung carcinoma.

In this study, PEGylated selenium nanoparticles (PSNP) was successfully prepared and combined with X-ray for effective anticancer efficacy in lung cancer cells. The particles were nanosized and observed in spherical shape. The combination of PSNP and X-ray effectively killed the cancer cells and decreased the cell viability in a concentration dependent manner. PSNP combined with X-ray showed a significantly higher apoptosis of cancer cells with around 23% of cells in late apoptosis stage. Consistently, Caspase-3 activity was significantly higher when exposed to X-ray than in the absence of X-ray. The caspase-3 activity has been doubled in the presence of X-ray and PSNPs were actively involved in the activation of effector caspase-3 and downstream target. Importantly, treatment with the combination of PSNP and X-ray showed predominant red fluorescence which is indicative of dead cells. The results clearly indicate the cytotoxic potential of PSNP + X-ray combination against lung cancer cells. Overall, novel strategy of combination of PSNP and X-ray could be an alternative and effective chemo-radiotherapy.

Attention to Automatic Movements in Parkinson's Disease: Modified Automatic Mode in the Striatum.

We investigated neural correlates when attending to a movement that could be made automatically in healthy subjects and Parkinson's disease (PD) patients. Subjects practiced a visuomotor association task until they could perform it automatically, and then directed their attention back to the automated task. Functional MRI was obtained during the early-learning, automatic stage, and when re-attending. In controls, attention to automatic movement induced more activation in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex, and rostral supplementary motor area. The motor cortex received more influence from the cortical motor association regions. In contrast, the pattern of the activity and connectivity of the striatum remained at the level of the automatic stage. In PD patients, attention enhanced activity in the DLPFC, premotor cortex, and cerebellum, but the connectivity from the putamen to the motor cortex decreased. Our findings demonstrate that, in controls, when a movement achieves the automatic stage, attention can influence the attentional networks and cortical motor association areas, but has no apparent effect on the striatum. In PD patients, attention induces a shift from the automatic mode back to the controlled pattern within the striatum. The shifting between controlled and automatic behaviors relies in part on striatal function.