Meta-analysis of evaluating neuron specific enolase as a serum biomarker for sepsis-associated encephalopathy.

INTRODUCTION: Brain dysfunction in sepsis is known as Sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk of death. Neuron specific enolase (NSE) may serve as an important neurocritical biomarker for detection and longitudinal monitoring in SAE patients. Our Meta-analysis aimed to explore the diagnostic and prognostic value of serum NSE in SAE patients. Currently, no systematic Review and Meta-analysis have been assessed that NSE as a biomarker of SAE. METHODS: The study protocol was registered in the PROSPERO database (CRD42023398736) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a systematic review and Meta-analysis to evaluate the serum NSE's diagnostic accuracy for SAE and prognostic strength for probability of death of septic patients. We systematic searched electronic bibliographic databases from PubMed, MEDLINE, Web of Science, Embase, Cochrane databases, CNKI, CQVIP, and WFSD. QUADAS-2 assessment tool was used to evaluate quality and risk of bias of the selected studies. Subgroup analyses, funnel plots, sensitivity analyses were also carried out. Review Manager version 5.4 and Stata16.0. was used for statistical analysis. RESULTS: This Meta-analysis included 22 studies with 1361 serum samples from SAE patients and 1580 serum samples from no-encephalopathy septic (NE) patients. The Meta-analysis showed that individuals with SAE had higher serum NSE level than NE controls (SMD 1.93 (95 % CI 1.51-2.35), P < 0.00001). In addition, there are 948 serum samples from survival septic patients and 446 serum samples from non-survival septic patients, septic patients with survival outcomes had lower serum NSE levels than those with death outcomes (SMD -1.87 (95 % CI -2.43 to -1.32), P < 0.00001). CONCLUSION: Our Meta-analysis reveals a significant association between elevated NSE concentrations and the increased likelihood of concomitant SAE and mortality during septic patients. This comprehensive analysis will equip ICU physicians with up-to-date insights to accurately identify patients at risk of SAE and implement appropriate intervention strategies to mitigate morbidity and improve neurological outcomes. However, it is important to note that the presence of substantial heterogeneity among studies poses challenges in determining the most effective discrimination cutoff values and optimal sampling collection time.

Circular RNA DNAH14 molecular mechanism in an experimental model of hepatocellular carcinoma treated with Cobalt chloride to mimic the hypoxia-like response of transcatheter arterial chemoembolization.

Transcatheter arterial chemoembolization (TACE) is the primary local treatment for patients with unresectable hepatocellular carcinoma (HCC). Numerous studies have demonstrated the pivotal role of circular RNAs (circRNAs) in TACE efficacy. This study aimed to investigate the function of circular RNA DNAH14 (circDNAH14) in TACE for HCC and to elucidate its molecular mechanisms. To simulate hypoxia conditions experienced during TACE, HCC cells were treated with cobalt chloride. The expression levels of circDNAH14, microRNA-508-3p (miR-508-3p), and Prothymosin Alpha (PTMA) were modulated via transfection for knockdown or overexpression. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, flow cytometry, and Transwell assays, along with epithelial-mesenchymal transition (EMT) evaluations, were employed to assess cell proliferation, apoptosis, invasion, migration, and EMT. The results indicated that hypoxia treatment downregulated the expression of circDNAH14 and PTMA while upregulating miR-508-3p. Such treatment suppressed HCC cell proliferation, invasion, migration, and EMT, and induced apoptosis. Knockdown of circDNAH14 or PTMA intensified the suppressive effects of hypoxia on the malignant behaviors of HCC cells. Conversely, upregulation of miR-508-3p or PTMA mitigated the effects of circDNAH14 overexpression and knockdown, respectively. Mechanistically, circDNAH14 was found to competitively bind to miR-508-3p, thereby regulating PTMA expression. In vivo, nude mouse xenograft experiments demonstrated that circDNAH14 knockdown augmented the hypoxia-induced suppression of HCC tumor growth. In conclusion, circDNAH14 mitigates the suppressive effects of hypoxia on HCC, both in vitro and in vivo, by competitively binding to miR-508-3p and regulating PTMA expression.

Current practices and challenges in application of trauma-informed care for accidentally injured patients: An exploratory qualitative study.

AIM: To explore the Chinese nurses' current practices and challenges to trauma-informed care (TIC) for accidentally injured patients, which can provide the way forward of improvement in the future. DESIGN: A qualitative study. METHODS: Sixteen Chinese nurses who had experience working with accidentally injured patients were invited into the semi-structured interviews. Following each interview, the dialogue was transcribed verbatim. Subsequently, we analysed the data in accordance with the principles of thematic analysis. RESULTS: Four common themes emerged from the analysis: (a) Awareness of patients' psychological trauma; (b) Recognition of psychological trauma; (c) Response to psychological trauma; (d) Perceived barriers to implementing TIC. This research indicated an urgent need for interventions in the future, such as TIC education and training, time constraints, heavy workload, emotional exhaustion and mood self-regulation, giving policy incentives, strengthening leadership support and internal cooperation. Identifying those factors of TIC practice among accidentally injured patients helps promote TIC development in hospitals.

Development of a Questionnaire for Measuring Trauma-Informed Care of Nurses Working with Traumatically Injured Patients.

Purpose: To develop a new questionnaire for assessing nurses' current situation of knowledge, attitude and practice related to trauma-informed care (TIC) for patients with traumatic injury. Methods: By literature review, qualitative interview and Delphi consultation, the 46 preliminary items about trauma-informed care of nurses working with traumatically injured patients were selected. After that, the preliminary questionnaire was distributed to 293 Chinese nurses in relevant departments. The collected data were analyzed by internal reliability, split-half reliability, structural validity and content validity. Results: The questionnaire was developed with a total of 30 items in 3 dimensions: 8 items in the TIC knowledge dimension, 10 items in the TIC attitude dimension and 12 items in the TIC practice dimension. The Cronbach's alpha coefficient was 0.939, and the content validity was 0.971. Conclusion: This designed questionnaire shews receptable reliability and validity, which could be used to assess the knowledge, attitude and practice of nurses in application of trauma-informed care for traumatically injured patients.

Renal pedicle lymphatic ligation for non-parasitic chyluria via retroperitoneal laparoscopic surgery: a single-center 12-year experience.

Background: Chyluria is a rare disease in which chylous is excreted in the urine. Currently, management of chyluria includes conservative treatments and surgical measures. This study aimed to report our experience in treating non-parasitic chyluria with retroperitoneal laparoscopic ligation of the renal lymphatic vessels. Methods: Data from 52 patients who underwent retroperitoneoscopic ligation of the renal lymphatic vessels for non-parasitic chyluria between December 2009 and May 2022 were reviewed. After general anesthesia, the patients were passively placed in the healthy lateral decubitus position and underwent three-port retroperitoneal laparoscopy. Detailed medical data, including demographic characteristics, intraoperative outcomes, postoperative data, and complications, were reviewed. Results: Fifty-two patients received surgery treatment at our institution. The mean disease course was 89.3 months. The mean age was 58.8 years, with females accounting for 57.7% (30/52); the majority of patients (33/52) had the laterality of chyluria on the left and 9 (17.3%) had a history of previous thoracic or abdominal surgery. Compared with the urine and blood data before the operation and on the first day after the operation, urinary protein, urinary tract infection, urinary red blood cells, hemoglobin, albumin, and serum total protein significantly improved 3 months after the operation. However, there were no significant differences in blood creatinine and blood urea nitrogen levels among the three groups. The mean surgery time was about 110.0 minutes, and the estimated total blood loss was 81.2 mL. The postoperative drainage volume was 229.9 mL. The average time to start a liquid diet and to be out of bed were 1.5 and 1.9 days, respectively. Transient postoperative gross hematuria occurred in eight patients, and complications occurred in five patients after surgery. The mean length of hospitalization was 6.6 days. The follow-up duration ranged from 3 to 152 months, and except for three patients who did not respond to treatment, the remaining patients had no recurrence and did not require reoperation. Conclusions: Our long-term follow-up results showed that renal pedicle lymphatic ligation via retroperitoneal laparoscopic surgery is an effective, safe, and reliable surgical option for patients with non-parasitic chyluria.

Lifestyle factors, serum parameters, metabolic comorbidities, and the risk of kidney stones: a Mendelian randomization study.

Background and objective: The early identification of modifiable risk factors is important for preventing kidney stones but determining causal associations can be difficult with epidemiological data. We aimed to genetically assess the causality between modifiable factors (lifestyle factors, serum parameters, and metabolic comorbidities) and the risk of kidney stones. Additionally, we aimed to explore the causal impact of education on kidney stones and its potential mediating pathways. Methods: We conducted a two-sample Mendelian randomization (MR) study to explore the causal association between 44 modifiable risk factors and kidney stones. The FinnGen dataset initially explored the causal relationship of risk factors with kidney stones and the UK Biobank dataset was used as the validation set. Then, a meta-analysis was conducted by combining discovery and validation datasets. We used two-step MR to assess potential mediators and their mediation proportions between education and kidney stones. Results: The combined results indicated that previous exposures may increase the risk of kidney stones, including sedentary behavior, urinary sodium, the urinary sodium/potassium ratio, the urinary sodium/creatinine ratio, serum calcium, 25-hydroxyvitamin D (25OHD), the estimated creatinine-based glomerular filtration rate (eGFRcrea), GFR estimated by serum cystatin C (eGFRcys), body mass index (BMI), waist circumference, type 2 diabetes mellitus (T2DM), fasting insulin, glycated hemoglobin, and hypertension. Coffee intake, plasma caffeine levels, educational attainment, and the urinary potassium/creatinine ratio may decrease the risk of kidney stones. Ranked by mediation proportion, the effect of education on the risk of kidney stones was mediated by five modifiable risk factors, including sedentary behavior (mediation proportion, 25.7%), smoking initiation (10.2%), BMI (8.2%), T2DM (5.8%), and waist circumference (3.2%). Conclusion: This study provides MR evidence supporting causal associations of many modifiable risk factors with kidney stones. Sedentary lifestyles, obesity, smoking, and T2DM are mediating factors in the causal relationship between educational attainment and kidney stones. Our results suggest more attention should be paid to these modifiable factors to prevent kidney stones.

Knockdown of lncRNA MALAT1 attenuates renal interstitial fibrosis through miR-124-3p/ITGB1 axis.

Renal interstitial fibrosis (RIF) considered the primary irreversible cause of chronic kidney disease. Recently, accumulating studies demonstrated that lncRNAs play an important role in the pathogenesis of RIF. However, the underlying exact mechanism of lncRNA MALAT1 in RIF remains barely known. Here, the aim of our study was to investigate the dysregulate expression of lncRNA MALAT1 in TGF-ß1 treated HK2/NRK-49F cells and unilateral ureteral obstruction (UUO) mice model, defining its effects on HK2/NRK-49F cells and UUO mice fibrosis process through the miR-124-3p/ITGB1 signaling axis. It was found that lncRNA MALAT1 and ITGB1 was significantly overexpression, while miR-124-3p was downregulated in HK2/NRK-49F cells induced by TGF-ß1 and in UUO mice model. Moreover, knockdown of lncRNA MALAT1 remarkably downregulated the proteins level of fibrosis-related markers, ITGB1, and upregulated the expression of epithelial marker E-cadherin. Consistently, mechanistic studies showed that miR-124-3p can directly binds to lncRNA MALAT1 and ITGB1. And the protect effect of Len-sh-MALAT1 on fibrosis related protein levels could be partially reversed by co-transfected with inhibitor-miR-124-3p. Moreover, the expression trend of LncRNA MALAT1/miR-124-3p/ITGB1 in renal tissues of patients with obstructive nephropathy (ON) was consistent with the results of cell and animal experiments. Taken together, these results indicated that lncRNA MALAT1 could promote RIF process in vitro and in vivo via the miR-124-3p/ITGB1 signaling pathway. These findings suggest a new regulatory pathway involving lncRNA MALAT1, which probably serves as a potential therapeutic target for RIF.

Poly- and perfluoroalkyl substances exposure during pregnancy and postpartum depression: Evidence from the Shanghai birth cohort.

BACKGROUND: Exposure to poly-and perfluoroalkyl substances (PFASs) has been linked to psychiatric disorders in the general population. Because women in the postpartum period are susceptible to mental disorders, we aimed to investigate the association between exposure to PFASs during pregnancy and postpartum depression (PPD). METHODS: Our study consisted of 2741 pregnant women who were enrolled in the Shanghai Birth Cohort during the early pregnancy and gave birth to a singleton live birth between 2013 and 2016. A total of 10 PFASs were measured in maternal plasma collected in early gestation by high-performance liquid chromatography/tandem mass spectrometry. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS) at 42 days after the child birth. We used multivariable logistic regression to estimate the association between exposure to PFASs and PPD, adjusted for potential confounders. Negative binomial regression was used to assess the association between PFASs exposure during pregnancy and EPDS subscales including anhedonia, anxiety, and depression. A quantile-based g-computation approach was used to evaluate the joint and independent effects of PFASs on PPD. RESULTS: Around 11.7% of the mothers had probable PPD (EPDS cut-off ≥10). Overall, exposure to PFASs in early pregnancy was not associated with PPD or EPDS subscales. Quantile g-computation method also showed that increasing PFASs mixture by one quartile was not associated with PPD (odds ratio, 1.08; 95% confidence interval: 0.91, 1.29). CONCLUSION: Our findings indicate that exposure to PFASs during pregnancy was not associated with PPD at 6 weeks postpartum.

Changes of anhedonia and cognitive symptoms in first episode of depression and recurrent depression, an analysis of data from NSSD.

BACKGROUND: Anhedonia and cognitive impairment are core features of major depressive disorder (MDD), and are essential to the treatment and prognosis. Here, we aimed to investigate anhedonia and its cognitive correlates between first episode of depression (FED) and recurrent depression (RD), which was part of the National Survey on Symptomatology of Depression. METHODS: In this study, 1400 drug naïve FED patients and 487 on medicine RD patients were included. Differences of anhedonia, cognitive symptoms and other clinical characteristics between groups were compared via Student's t-test, or the chi-square test as appropriate. Partial correlation analysis was used to analyze the correlations between anhedonia and cognitive symptoms after adjusting for potential confounders. A stepwise logistic regression analysis was performed to identify relapse risk factors among symptomatic variables, demographic factors, clinical characteristics and medication use. RESULTS: Compared to FED, RD patients displayed more comprehensive depressive, impaired cognitive and anhedonia symptoms. Cognitive symptoms were significantly related with the anhedonia symptoms with varying aspects. Patients taking emotional stabilizers displayed more abnormal cognitive symptoms, followed by benzodiazepines, and finally SSRIs, SNRIs and TCAs. The effect of drug use on anhedonia is not as extensive as that of cognitive symptoms. CONCLUSION: Collectively, the results of this investigation advance the knowledge on changes in anhedonia and cognitive symptoms in MDD. LIMITATIONS: As this is a cross sectional study, it is difficult to draw any causal conclusions between cognitive impairment and anhedonia in MDD, and to ascertain the worse cognitive performances identified here were induced by current drug use.

Gut Microbiota and Tumor Immune Escape: A New Perspective for Improving Tumor Immunotherapy.

The gut microbiota is a large symbiotic community of anaerobic and facultative aerobic bacteria inhabiting the human intestinal tract, and its activities significantly affect human health. Increasing evidence has suggested that the gut microbiome plays an important role in tumor-related immune regulation. In the tumor microenvironment (TME), the gut microbiome and its metabolites affect the differentiation and function of immune cells regulating the immune evasion of tumors. The gut microbiome can indirectly influence individual responses to various classical tumor immunotherapies, including immune checkpoint inhibitor therapy and adoptive immunotherapy. Microbial regulation through antibiotics, prebiotics, and fecal microbiota transplantation (FMT) optimize the composition of the gut microbiome, improving the efficacy of immunotherapy and bringing a new perspective and hope for tumor treatment.

Transabdominal Laparoscopic Ureteroureterostomy With the Intraoperative Retrograde Ureteroscopy-Assisted Technique for Multiple Ureteral Polyps: A Single-Center 10 Years Experiences.

Background: The purpose of this study was to report our experience in treating multiple ureteral polyps with transabdominal laparoscopic ureteroureterostomy (LAP-UU) with intraoperative retrograde ureteroscopy (RU)-assisted technique. Methods: The data of 32 patients who underwent transabdominal LAP-UU with the intraoperative RU-assisted technique due to multiple ureteral polyps between January 2011 and March 2021 were reviewed at our institute. After administration of anesthesia, patients were placed in a passive position and underwent a three-port transabdominal laparoscopy with RU. Detailed data were reviewed, such as demographic characteristics, intraoperative outcomes, postoperative data, complications, and pathology reports. Results: Thirty-two patients were diagnosed with multiple ureteral polyps underwent this surgery method at our institution. The mean duration of symptoms at the time of diagnosis was approximately 7.1 months. The mean age of patients was 42.4 years, with men accounting for 68.8% (22/32), lesion of left for 56.3% (18/32), and the upper ureter for 62.5% (20/32). Furthermore, the median length of the polyps was 3.6 cm, the mean operative time was 174.6 min, and the estimated blood loss (EBL) was about 86.8 ml. The mean time to begin a liquid diet and to be out of bed were 1.7 and 2.3 days, respectively. The average length of hospital stay was 6.3 days. The ureteral stent was removed by cystoscope 2-3 months after surgery. Follow-up duration ranged from 3 to 112 months and none of the patients required another surgery for recurrence. Conclusion: Transabdominal LAP-UU combined with the intraoperative RU-assisted technique is an effective, safe, and reliable surgical option for patients with multiple ureteral polyps. Further long-term follow-up is recommended.

MicroRNA miR-4709-3p targets Large Tumor Suppressor Kinase 2 (LATS2) and induces obstructive renal fibrosis through Hippo signaling.

Obstructive renal fibrosis is the consequence of abnormal extracellular matrix assembly, which eventually results in renal failure, acute, and end­stage renal infection. MicroRNAs (miRNAs), a particular category of small RNAs, modulate the expression of genes post-transcriptionally and regulate biological activities, including fibrogenesis. The study probed to estimate the key functions of miR-4709-3p in obstructive renal fibrosis. This investigation used TGF-ß1 stimulated HK-2 in-vitro model, unilateral ureteral occlusion (UUO) mice model, and human Diabetic nephropathy (DN) and Renal interstitial fibrosis (RIF) specimens to depict the abundance of the miR-4709-3p level using FISH and RT-qPCR. MiR-4709-3p mimics and inhibitors were utilized to evaluate the functions of miR-4709-3p in-vitro. Luciferase assay was exploited to verify miR-4709-3p and LATS2 3'UTR binding. Finally, to depict the functions of miR-4709-3p in-vivo, the UUO model was injected with miR-4709-3p inhibitors. Results exhibited the upregulation of miR-4709-3p in UUO-induced in-vivo model, TGF-ß1 stimulated HK-2, and human RIF and DN samples. Moreover, it was determined that modulating miR-4709-3p regulated the level of fibrosis markers. Luciferase assay miR-4709-3p modulates renal fibrosis by targeting LATS2. Finally, it was found that miR-4709-3p regulates obstructive renal fibrosis through the Hippo signaling pathway. Overall, the study concludes that aberrant miR-4709-3p expression plays an essential function in the renal fibrosis progression, and miR-4709-3p overexpression could advance obstructive renal fibrosis via LATS2 targeting in Hippo signaling pathway. Therefore, miR-4709-3p inhibition may be a potential renal fibrosis therapy target.

α-Klotho released from HK-2 cells inhibits osteogenic differentiation of renal interstitial fibroblasts by inactivating the Wnt-ß-catenin pathway.

Randall's plaques (RP) are well established as precursor lesions of idiopathic calcium oxalate (CaOx) stones, and the process of biomineralization driven by osteogenic-like cells has been highlighted in RP formation, but the mechanism is poorly understood. Given the inhibitory role of α-Klotho (KL), an aging suppressor protein with high expression in kidneys, in ectopic calcification and the close association between KL gene polymorphisms and urolithiasis susceptibility, we determined the potential role of KL in RP formation. This study found that both soluble KL (s-KL) and transmembrane KL (m-KL) were downregulated, and that s-KL but not m-KL was inversely correlated with upregulation of osteogenic markers in RP tissues. Additionally, s-KL expression was markedly suppressed in human renal interstitial fibroblasts (hRIFs) and slightly suppressed in HK-2 cells after osteogenic induction, intriguingly, which was echoed to the greater osteogenic capability of hRIFs than HK-2 cells. Further investigations showed the inhibitory effect of s-KL on hRIF osteogenic differentiation in vitro and in vivo. Moreover, coculture with recombinant human KL (r-KL) or HK-2 cells suppressed osteogenic differentiation of hRIFs, and this effect was abolished by coculture with KL-silenced HK-2 cells or the ß-catenin agonist SKL2001. Mechanistically, s-KL inactivated the Wnt-ß-catenin pathway by directly binding to Wnt2 and upregulating SFRP1. Further investigations identified activation of the Wnt-ß-catenin pathway and downregulation of SFRP1 and DKK1 in RP tissues. In summary, this study identified s-KL deficiency as a pathological feature of RP and revealed that s-KL released from HK-2 cells inhibited osteogenic differentiation of hRIFs by inactivating the Wnt-ß-catenin pathway, not only providing in-depth insight into the role of s-KL in renal interstitial biomineralization but also shedding new light on the interaction of renal tubular epithelial cells with interstitial cells to clarify RP formation.

Phosphoproteomics identifies potential downstream targets of the integrin α2ß1 inhibitor BTT-3033 in prostate stromal cells.

BACKGROUND: Integrin α2ß1 inhibitor BTT-3033 (1-(4-fluorophenyl)-N-methyl-N-[4[[(phenylamino)carbonyl]amino]phenyl]-1H-pyrazole-4-sulfonamide) was recently reported to inhibit neurogenic and thromboxane A2-induced human prostate smooth muscle contraction, and thus represents a target with a different inhibition spectrum than that of α1-blockers in benign prostate hyperplasia (BPH) treatments. Clarifying the underlying mechanisms of the inhibition effects will provide insights into the role of integrin α2ß1 in prostate contraction and enable new intracellular targets for smooth muscle contraction to be explored. METHODS: ProteomeHD was used to predict and enrich the top co-regulated proteins of integrin α2 (ITGA2). A phosphoproteomic analysis was conducted on human prostate stromal cells (WPMY-1) treated with 1 or 10 µM of BTT-3033 or solvent for controls. A clustering analysis was conducted to identify the intracellular targets that were inhibited in a dose-dependent manner. Gene ontology (GO) and annotation enrichments were conducted to examine any functional alterations and identify possible downstream targets. A Kinase-substrate enrichment analysis (KSEA) was conducted to identify kinases-substrate relationships. RESULTS: Enrichments of the actin cytoskeleton and guanosine triphosphatases (GTPases) signaling were predicted from the co-regulated proteins with ITGA2. LIM domain kinases, including LIM domain and actin-binding 1 (LIMA1), zyxin (ZYX), and thyroid receptor-interacting protein 6 (TRIP6), which are functionally associated with focal adhesions and the cytoskeleton, were present in the clusters with dose-dependent phosphorylation inhibition pattern. 15 substrates were dose-dependently inhibited according to the KSEA, including polo-like kinase 1 (PLK1), and GTPases signaling proteins, such as disheveled segment polarity protein 2 (DVL2). CONCLUSIONS: In this study, we proposed that the mechanisms underlying the contractile and proliferative effects of integrin α2ß1 are the LIM domain kinases, including the ZYX family, and substrates, including PLK1 and DVL2.

Online Learning Performances of Children and Adolescents With Attention Deficit Hyperactivity Disorder During the COVID-19 Pandemic.

To investigate attention deficit hyperactivity disorder (ADHD) core symptoms that impair executive function (EF), emotional state, learning motivation, and the family and parenting environment of children and adolescents with ADHD, both with and without severe difficulties. This will be explored within an online learning environment during the period of COVID-19 pandemic. A total of 183 ADHD children diagnosed using DSM-V criteria were selected and divided into 2 groups high difficulties during online learning (HDOL) and low difficulties during online learning (LDOL) according to the answer of Home Quarantine Investigation of the Pandemic (HQIP). The participants filled out a set of questionnaires to assess their emotional state and learning motivation, and their parents also filled out the questionnaires about ADHD core symptoms, EF, and family and parenting environment. Compared with ADHD children in the LDOL group, the children in the HDOL group had significant symptoms of inattention, hyperactivity, oppositional defiant, behavioral and emotional problems according to the Swanson, Nolan, and Pelham Rating Scale (SNAP). They also had more severely impaired EF according to the Behavior Rating Inventory of Executive Function (BRIEF), more difficulties and disturbances in the family by the Chinese version of Family Environment Scale (FES-CV), and lower parenting efficacy and satisfaction by Parenting Sense of Competence (PSOC). With regard to the self-rating questionnaires of children and adolescents, the HDOL group reported lower learning motivation according to the Students Learning Motivation Scale (SLMS). By Screening for Child Anxiety-Related Emotional Disorders and Depression Self-Rating Scale for Children (DSRSC), those in HDOL presented more negative emotions. The HDOL group spent significantly more time on both video games and social software per day and significantly less time on multiple activities per week, when compared to those in the LDOL group. This study demonstrated that ADHD children and adolescents with HDOL had more inattention-related behaviors, more severe emotional problems and EF impairment, weaker learning motivation, and poorer family and parenting environment. Meanwhile, digital media use should be supervised and appropriate extracurricular activities should be encouraged by parents and schools.

Liproxstatin-1 attenuates unilateral ureteral obstruction-induced renal fibrosis by inhibiting renal tubular epithelial cells ferroptosis.

Renal fibrosis is a common pathological process that occurs with diverse etiologies in chronic kidney disease. However, its regulatory mechanisms have not yet been fully elucidated. Ferroptosis is a form of non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. It is currently unknown whether ferroptosis is initiated during unilateral ureteral obstruction (UUO)-induced renal fibrosis and its role has not been determined. In this study, we demonstrated that ureteral obstruction induced ferroptosis in renal tubular epithelial cells (TECs) in vivo. The ferroptosis inhibitor liproxstatin-1 (Lip-1) reduced iron deposition, cell death, lipid peroxidation, and inhibited the downregulation of GPX4 expression induced by UUO, ultimately inhibiting ferroptosis in TECs. We found that Lip-1 significantly attenuated UUO-induced morphological and pathological changes and collagen deposition of renal fibrosis in mice. In addition, Lip-1 attenuated the expression of profibrotic factors in the UUO model. In vitro, we used RSL3 treatment and knocked down of GPX4 level by RNAi in HK2 cells to induce ferroptosis. Our results indicated HK2 cells secreted various profibrotic factors during ferroptosis. Lip-1 was able to inhibit ferroptosis and thereby inhibit the secretion of the profibrotic factors during the process. Incubation of kidney fibroblasts with culture medium from RSL3-induced HK2 cells promoted fibroblast proliferation and activation, whereas Lip-1 impeded the profibrotic effects. Our study found that Lip-1 may relieve renal fibrosis by inhibiting ferroptosis in TECs. Mechanistically, Lip-1 could reduce the activation of surrounding fibroblasts by inhibiting the paracrine of profibrotic factors in HK2 cells. Lip-1 may potentially be used as a therapeutic approach for the treatment of UUO-induced renal fibrosis.

Knockdown of lncRNA XIST inhibited apoptosis and inflammation in renal fibrosis via microRNA-19b-mediated downregulation of SOX6.

BACKGROUND: Kidney damage often develops into renal fibrosis. Apoptosis and inflammatory response are the main factors driving the process of renal fibrosis. Here we showed that lncRNA XIST/ miR-19b / SOX6 signal axis regulated apoptosis and inflammation of renal fibrosis. METHODS: HK-2 cells were treated with TGF-ß1 to construct cell fibrosis model, and UUO surgery was performed to construct mouse renal fibrosis model. The expression of XIST, miR-19b and SOX6 were examined by qPCR. And levels of fibrosis-related proteins were detected by western blotting. Levels of IL-1ß and TNF-α were assessed by qPCR and ELISA, respectively. Renal pathology and fibrosis were evaluated by HE and Masson staining. Flow cytometry and TUNEL staining were employed to evaluate cell apoptosis in cell fibrosis model and mouse renal fibrosis model, respectively. Besides, dual luciferase reporter assay was employed to verify whether XIST had a binding site to miR-19b, and whether miR-19b had a binding site to SOX6. RESULTS: Here we showed that XIST and SOX6 were upregulated in both HK-2 cells treatment of TGF-ß1 and kidneys of UUO mice, while miR-19b was downregulated. Dual luciferase reporter assay displayed that XIST directly bound to miR-19b, and SOX6 was the target of miR-19b. Knockdown of XIST inhibited apoptosis, inflammation and fibrosis in HK-2 cells treatment of TGF-ß1 via miR-19b-mediated downregulation of SOX6, while inhibition of miR-19b reversed the effect. Similarly, knockdown of XIST in vivo inhibited apoptosis, inflammation and fibrosis in kidneys of UUO mice via miR-19b-mediated downregulation of SOX6. DISCUSSION: These results provided evidence that knockdown of XIST inhibited apoptosis and inflammation of renal fibrosis via miR-19b-mediated downregulation of SOX6.

Long Non-coding RNA: An Emerging Contributor and Potential Therapeutic Target in Renal Fibrosis.

Renal fibrosis (RF) is a pathological process that culminates in terminal renal failure in chronic kidney disease (CKD). Fibrosis contributes to progressive and irreversible decline in renal function. However, the molecular mechanisms involved in RF are complex and remain poorly understood. Long non-coding RNAs (lncRNAs) are a major type of non-coding RNAs, which significantly affect various disease processes, cellular homeostasis, and development through multiple mechanisms. Recent investigations have implicated aberrantly expressed lncRNA in RF development and progression, suggesting that lncRNAs play a crucial role in determining the clinical manifestation of RF. In this review, we comprehensively evaluated the recently published articles on lncRNAs in RF, discussed the potential application of lncRNAs as diagnostic and/or prognostic biomarkers, proposed therapeutic targets for treating RF-associated diseases and subsequent CKD transition, and highlight future research directions in the context of the role of lncRNAs in the development and treatment of RF.

Callous-unemotional traits in Chinese preschool children with attention-deficit/hyperactivity disorder.

BACKGROUND: Children with early onset of Callous-Unemotional (CU) traits are at a higher risk for long-term, persistent psychosocial problems. The current study aimed to explore the characteristics of CU in preschool children with Attention Deficit Hyperactivity Disorder (ADHD) and the diagnostic significance of CU traits in ADHD. METHODS: A total of 176 preschool children (89 with ADHD and 87 Typically Developing Children [TDC]) aged 4-5 years old were recruited to the study. The participants were assessed for CU traits, emotional and behavioral problems, and how their executive functioning was associated with ADHD using multiple assessment scales. Multiple linear regression analysis was performed to assess the incremental validity of the Inventory of Callous-Unemotional Traits (ICU), adjusting for possible covariates by child's sex, conduct problems, and oppositional defiant symptoms. RESULTS: The results showed that there was a significant difference of ICU scores between the ADHD and TDC groups (F = 30.12, P < 0.001). In terms of callousness, ADHD + Oppositional Defiant Disorder (ODD) group showed a significant high score, and the ADHD only group scored significantly higher than the TDC group (F = 20.42, P < 0.001). The ICU was negatively associated with the prosocial behaviour subscale (γ = - 0.57, P < 0.01) and showed low to moderate positive correlations with emotional and behavioural problems, as well as executive function (γ = 0.24-0.67, P < 0.05). The ICU scores explained 6% of the incremental validity in ADHD symptoms. The diagnostic value of the ICU for ADHD was medium and acceptable. CONCLUSIONS: The current study indicated that early identification of CU traits may help clinicians better understand symptoms and behavioural problems in children with ADHD. CU traits therefore could be considered as a useful assessment tool for ADHD.

NEAT1 functions as a key mediator of BMP2 to promote osteogenic differentiation of renal interstitial fibroblasts.

Aim: To clarify the mechanism of NEAT1, an aberrantly upregulated lncRNA in Randall's plaques (RP) similar to biomineralization, in mediating osteogenic differentiation of human renal interstitial fibroblasts. Materials & methods: A comprehensive strategy of bioinformatic analysis and experimental verification was performed. Results:BMP2 silence abolished the osteogenic differentiation of human renal interstitial fibroblasts promoted by NEAT1. Mechanically, NEAT1 not only induced the nucleolar translocation of EGR1 binding to BMP2 promotor, but also functioned as a sponge of miR-129-5p in the cytoplasm to promote BMP2 expression. Moreover, there was a positive correlation between NEAT1 and BMP2 expression in RP instead of normal renal papilla. Conclusion:NEAT1 acted as a key mediator of BMP2 to promote human renal interstitial fibroblast osteogenic differentiation, through which NEAT1 might be involved in RP formation.

Lay abstract Kidney stones affect one in ten people in the world, and calcium oxalate (CaOx) stones account for 80% of kidney stones. Calcium and oxalate originate from Randall's plaques (RP) which was identified as an anchor for CaOx in renal papilla (parts of the kidney where collecting ducts open to allow urine to flow to the ureter). RP formation shares similarities with bone formation and blood vessel calcification (hardening caused by calcium salt accumulation). Our findings revealed that long non-coding RNA (long nucleotide sequence not made into protein) NEAT1 controlled genes relating to bone formation in kidney cells known as human renal interstitial fibroblasts which are involved in kidney repair processes. This finding implies human renal interstitial fibroblasts might contribute to kidney calcium phosphate deposits prior to RP formation. Collectively, our study provided a new understanding of how NEAT1 might be involved in RP formation by changing the function of osteogenic-like cells in the kidney.