Association between Psoriasis and Renal Functions: An Integration Study of Observational Study and Mendelian Randomization.

Psoriasis is an autoimmune-mediated disease with several comorbidities in addition to typical skin lesions. Increasing evidence shows the relationships between psoriasis and renal functions, but the relationship and causality remain unclear. We aimed to investigate the associations and causality between psoriasis and four renal functions, including the estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), urine albumin to creatinine ratio (UACR), and chronic kidney disease (CKD). For the population-based study, we analyzed the National Health and Nutrition Examination Survey (NHANES) data from five cycles (2003-2006 and 2009-2014) on psoriasis and renal functions. Subgroup analyses were conducted among different categories of participants. Meanwhile, a bidirectional two-sample Mendelian randomization (TSMR) study in European populations was also performed using summary-level genetic datasets. Causal effects were derived by conducting an inverse-variance weighted (MR-IVW) method. A series of pleiotropy-robust MR methods was employed to validate the robustness. Multivariable MR (MVMR) was conducted to complement the result when five competing risk factors were considered. A total of 20,244 participants were enrolled in the cross-sectional study, where 2.6% of them had psoriasis. In the fully adjusted model, participants with psoriasis had significantly lower eGFR (p = 0.025) compared with the healthy group. Individuals who are nonoverweight are more likely to be affected by psoriasis, leading to an elevation of BUN (Pint = 0.018). In the same line, TSMR showed a negative association between psoriasis and eGFR (p = 0.016), and sensitive analysis also consolidated the finding. No causality was identified between psoriasis and other renal functions, as well as the inverse causality (p > 0.05). The MVMR method further provided quite consistent results when adjusting five confounders (p = 0.042). We detected a significant negative effect of psoriasis on eGFR, with marginal association between BUN, UACR, and CKD. The adverse of psoriasis on the renal should merit further attention in clinical cares.

Quantitative analysis of IKZF1 gene deletions in pediatric B-cell precursor acute lymphoblastic leukemia: higher levels are associated with a poorer prognosis.

To assess the prognostic effect of different levels of IKZF1 gene deletions in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). IKZF1 Δ2-8/ALB deletions were quantified using multiplex real-time quantitative PCR in newly diagnosed pediatric BCP-ALL patients. Seventy-four patients with IKZF1 deletions ≥ 0.01% were included. Clinical characteristics, laboratory data, and treatment outcomes were analyzed. The patients were divided into two groups: IKZF1 deletions <1% (group A) and ≥1% (group B). Group B patients had a higher BCR-ABL1 positive rate than group A patients. The proportions of patients who had an age at onset ≥10 years old, and white blood cell count ≥50 × 109/L were significantly higher in group B than in group A. The 3-year overall survival (OS) and 3-year event-free survival (EFS) rates in group B were 79 ± 8.8% and 62.4 ± 9.7%, respectively, being significantly lower than those in group A (97.7 ± 2.2% and 83.2 ± 5.8%, respectively). The level of IKZF1 deletions ≥1% and the central nervous system leukemia were independent risk factors of EFS. Pediatric BCP-ALL patients with high levels of IKZF1 gene deletions have a poorer prognosis than those with low levels.

Hsa_circ_001659 serves as a novel diagnostic and prognostic biomarker for colorectal cancer.

Colorectal cancer (CRC) is prevalent worldwide and novel diagnostic and prognostic biomarkers are needed to improve precision medicine. Circular RNAs (circRNAs) are currently being considered as emerging tumor biomarkers. Herein, we aimed to explore the possible clinical application of circRNAs in the early diagnosis and prognostic prediction of CRC. First, candidate circRNA was selected by integrating analysis of Gene Expression Omnibus (GEO) database using GEO2R program. ROC curve analysis demonstrated the predictive values and likelihood ratios of circ_001659 were satisfactory for the diagnosis of CRC, including patients in early-stage disease or patients with carcinoembryonic antigen (CEA)-negative status. Moreover, serum circ_001659 may be a novel biomarker in the assessment of successful treatment and remission of cancer tracking. We further investigated the oncogenic role of circ_001659. In vivo and in vitro experiments indicated that circ_001659 could promote CRC cell invasion and migration. Mechanistically, circ_001659 was localized in the nucleus, recruited the RBBP5 to Vimentin promoter and increased H3K4 trimethylation level on the Vimentin promoter region, which epigenetically activated Vimentin transcription. Our findings demonstrate that circ_001659 could be a useful serum biomarker for CRC diagnosis and prognosis. Targeting circ_001659 and its pathway may be meaningful for treating patients with CRC.

Malignancy-associated hemophagocytic lymphohistiocytosis in children: a 10-year experience of a single pediatric hematology center.

Objective: Malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH) in children is a relatively rare but life-threatening secondary hemophagocytic lymphohistiocytosis (sHLH). Until now, only a limited number of cases regarding children with M-HLH has been reported. Methods: We conducted a retrospective study of 27 children with M-HLH, who admitted to our center between July 2007 and October 2019. The clinical data and laboratory data were analyzed. Results: The median age of the children with M-HLH was 7 years. Underlying diseases included myeloid malignancy (n = 6), lymphoid malignancy (n = 18) and unknown type lymphoma (n = 3). The one-year mortality rate was 56%. All patients had persistent fever. The clinical manifestations included hepatomegaly (89%), splenomegaly (67%) and central nervous system symptoms (56%). Thirteen children (48%) had Epstein-Barr virus (EBV) infection. No significant differences were observed between EBV-positive and negative M-HLH patients in terms of most clinical indicators. However, EBV-positive M-HLH patients showed prolonged activated partial thromboplastin time (APTT) and more hemophagocytosis in the bone marrow (BM) in contrast to EBV-negative patients. Eighteen patients (67%) received the HLH-94/04 regimen as the initial treatment. There were no significant differences in the overall survival (OS) between EBV-positive and negative patients. Patients with prolonged APTT had a significantly poorer OS than other patients (p = 0.012). Conclusions: The M-HLH children with EBV infection are more likely to have prolonged APTT and more hemophagocytosis in BM. The M-HLH children had a poor prognosis, especially those with prolonged APTT.

Evaluation on the diagnostic and prognostic values of long non-coding RNA BLACAT1 in common types of human cancer.

A growing number of evidence has indicated that long non-coding RNAs (lncRNA) may have many functions in the development and progression of cancer, and cloud serve as good diagnostic and prognostic biomarkers in cancers. However, these studies often revealed the changes of lncRNAs within a specific cancer type. Here, we focused on BLACAT1 and provided a comprehensive pan-cancer analysis to evaluate the diagnostic and prognostic values of BLACAT1. The expression data of BLACAT1 were came from the quantitative real-time polymerase chain reaction (qRT-PCR) and The Cancer Genome Atlas (TCGA) database, respectively. Our results showed that the change of serum BLACAT1 expression was similar to those in matched tissues. The expression level of BLACAT1 both in serum and tissues in multiple cancer types were significantly upregulated compared to those of matched non-cancer participants. The serum BLACAT1 had a high diagnostic performance among these 12 types of cancer. The relative AUC of serum BLACAT1 in cancer patients ranged from 0.833 to 0.967 compared to that in healthy subjects. Surprisingly, Kaplan-Meier survival analysis revealed that the high expression level of BLACAT1 was significantly associated with poor overall survival only in uterine corpus endometrial carcinoma (p = 0.002, log-rank test). These findings demonstrated that BLACAT1 could act as a non-specific diagnostic biomarker for cancers and a potential biomarker for prognosis prediction of endometrial cancer.

Serum long non-coding RNAs MALAT1, AFAP1-AS1 and AL359062 as diagnostic and prognostic biomarkers for nasopharyngeal carcinoma.

Circulating RNAs in serum, plasma or other body liquid have emerged as useful and highly promising biomarkers for noninvasive diagnostic application. Herein, we aimed to establish a serum long non-coding RNAs (lncRNAs) signature for diagnosing nasopharyngeal carcinoma (NPC). In this study, we recruited a cohort of 101 NPC patients, 20 patients with chronic nasopharyngitis (CN), 20 EBV carriers (EC) and 101 healthy controls. qRT-PCR was performed with NPC cells and serum samples to screen a pool of 38 NPC-related lncRNAs obtained from the LncRNADisease database. A profile of three circulating lncRNAs (MALAT1, AFAP1-AS1 and AL359062) was established for NPC diagnosis. By Receiver Operating Characteristic (ROC) curve analysis, this three-lncRNA signature showed high accuracy in discriminating NPC from healthy controls (AUC = 0.918), CN (AUC = 0.893) or EC (AUC = 0.877). Furthermore, high levels of these three lncRNAs were closely related to advanced NPC tumor node metastasis stages and EBV infection. Serum levels of these three lncRNAs declined significantly in patients after therapy. Our present study indicates that circulating MALAT1, AFAP1-AS1 and AL359062 may represent novel serum biomarkers for NPC diagnosis and prognostic prediction after treatment.

Meta-signature LncRNAs serve as novel biomarkers for colorectal cancer: integrated bioinformatics analysis, experimental validation and diagnostic evaluation.

The aim of this study is to explore the differentially expressed lncRNAs, which may have potential biological function and diagnostic value in colorectal cancer (CRC). Through integrated data mining, we finally identified nine differentially expressed lncRNAs and their potential mRNA targets. After a series of bioinformatics analyses, we screened significant pathways and GO terms that are related to the up-regulated and down-regulated transcripts respectively. Meanwhile, the nine lncRNAs were validated in 30 paired tissues and cell lines by qRT-PCR and the results were basically consistent with the microarray data. We also tested the nine lncRNAs in the serum of 30 CRC patients matched with the CRC tissue, 30 non-cancer patients and 30 health controls. Finally, we found that BLACAT1 was significant for the diagnosis of CRC. The area under the curve (AUC), sensitivity and specificity were 0.858 (95% CI: 0.765-0.951), 83.3% and 76.7% respectively between CRC patients and health controls. Moreover, BLACAT1 also had distinct value to discriminate CRC from other non-cancer diseases. The results indicated that the differentially expressed lncRNAs and their potential target transcripts could be considered as potential therapeutic targets for CRC patients. Meanwhile, lncRNA BLACAT1 might represent a new supplementary biomarker for the diagnosis of CRC.

Remission and relapse of hemophagocytic lymphohistiocytosis in a patient harboring a PRF1 homozygous mutation: a case report.

The aim of this paper was to describe a case of familial hemophagocytic lymphohistiocytosis (HLH) in a pediatric patient with a PRF1 homozygous mutation. An 8-year-old boy diagnosed with HLH was in remission after undergoing nonspecific treatment; however, merely 2 months later, he was presented at our hospital with a relapse of HLH. His genetic analysis showed that he had a homozygous mutation c.1066C>T in the PRF1 gene. Timely distinction of primary HLH from secondary HLH is critical.

Increased cysteinyl leukotriene concentration and receptor expression in tonsillar tissues of Chinese children with sleep-disordered breathing.

BACKGROUND: Evidence suggests that increased leukotriene level and receptor protein expression emerged in the adenotonsillar tissue of children with sleep-disordered breathing (SDB). Nevertheless, few studies have investigated the contribution of disease severity in the cysteinyl leukotriene (CysLT) production and cysteinyl leukotriene receptor (CysLTR) expression. Furthermore, the relationship between local upper-airway and systemic inflammatory responses remains undefined. METHODS: A prospective, observational study that included standard questionnaires, physical examinations and overnight polysomnography. CysLTs were determined from serum, urine and tonsillar homogenate supernatant by means of enzyme-linked immunosorbent assays. The protein expressions of CysLTR were measured using Western blot analysis. RESULTS: Children with SDB had increased intratonsillar CysLT levels as well as CysLT subtype 1 receptor (CysLT1-R) and CysLT subtype 2 receptor (CysLT2-R) protein expression than the control group. CysLT concentration was positively correlated with body mass index z-score and apnea-hypopnea index (r=0.454 and 0.487, p<0.001 respectively), and negatively correlated with pulse oximetric saturation nadir (r=-0.518, p<0.001). Upper-airway intratonsillar CysLT production was positively correlated with systemic production (vs. urinary LTE4: r=0.456, p<0.001; vs. serum CysLTs: r=0.440, p<0.001). Immunoblots showed that CysLT1-R protein expressions were modestly higher in the severe group when compared to the mild group. In contrast, there were no differences in CysLT2-R protein appearing among the SDB subgroups. CONCLUSIONS: Increased CysLT level and receptor expression in upper-airway tonsillar tissues are related to disease severity in SDB children. The local and systemic CysLT production were positively correlated.

[Advances of study on glucose and lipids metabolism of chlorogenic acid regulating].

Chlorogenic acid (CGA) could be a phenolic acid, which was widely found in food of plant origin and coffee drinks. The studies showed that biological activities of chlorogenic acid could be good for human health. The biological activity of regulating glucose and lipids metabolism and enhancing the sensitivity of insulin of CGA were focused the scientific evidence of preventing and treating the chronic diseases such as obesity and diabetes through the diet. The evolvement of study concerning the relation between CGA and glucose and lipids metabolism, and its mechanism were reviewed in this article.