A gradient model of renal ischemia reperfusion injury to investigate renal interstitial fibrosis.

Background: The progression from acute kidney injury to chronic kidney disease poses a significant health challenge. Nonetheless, a constraint in existing animal models of renal ischemia/reperfusion (I/R) injury is the necessity for a severe injury, almost reaching a life-threatening level, to trigger the subsequent onset of renal fibrosis. Hence, we explored an adapted gradient approach to induce I/R injury, aiming to promote the progression of renal fibrosis while preserving the overall normal functioning of the kidney. Methods: In each group, 6-8 male C57BL/6 mice were used for model construction, with all undergoing sodium pentobarbital anesthesia and left kidney removal. Subsequently, a silk thread was passed beneath the lower renal branch, elevating the right kidney under a 20-g weight's tension via a pulley system for durations of 30, 40, or 60 min. Afterwards, we lowered the kidney, sutured the wound, and administered intraperitoneal saline. Mice in different groups were euthanized following reperfusion for 1, 3, 7, or 28 days. Results: We observed a complete cessation of blood flow in the lower pole, while an incomplete cessation in the upper pole in the elevated kidney. Significant renal impairment was evident on day 1 with a 60min ischemic period (187.0 ± 65.3 vs 17.9 ± 4.8 µmol/L serum creatinine in normal; p < .001), but not with 30 or 40min. On day 1, tubular necrosis and hyaline cast formation was evident in both lower and upper poles. On day 3, renal function returned to normal and remained normal through day 28. Histologic damage resolved in the upper pole over days 3 to 7, resulting in normal histology on day 28. By contrast, there was sustained tubular damage tubular in the lower pole on days 3 and 7, which failed to resolve and led to significant renal fibrosis by day 28. Conclusion: We created a model demonstrating clinically "silent" renal fibrosis.

Multimodal High-Resolution Imaging in Retinitis Pigmentosa: A Comparison Between Optoretinography, Cone Density, and Visual Sensitivity.

Purpose: Retinitis pigmentosa (RP), the most common inherited retinal disease, is characterized by progressive photoreceptor degeneration. It remains unknown to what extent surviving photoreceptors transduce light and support vision in RP. To address this, we correlated structure and functional measures using adaptive optics scanning laser ophthalmoscopy (AOSLO), adaptive optics microperimetry, and adaptive optics optical coherence tomography (AO-OCT)-based optoretinograms (ORGs). Methods: Four patients with RP were imaged with AOSLO across the visual field covering the transition zone (TZ) of normal to diseased retina. Cone density was estimated in discrete regions spanning the TZ. Visual sensitivity was assessed by measuring increment thresholds for a 3-arcmin stimulus targeted via active eye tracking in AOSLO. ORGs were measured at the same locations using AO-OCT to assess the cones' functional response to a 528 ± 20-nm stimulus. Individual cone outer segment (COS) lengths were measured from AO-OCT in each subject. Results: Cone density was significantly reduced in patients with RP. Density reduction correlated with TZ location in 3 patients with RP, while a fourth had patches of reduced density throughout the retina. ORG amplitude was reduced in regions of normal and reduced cone density in all patients with RP. ORG response and COS length were positively correlated in controls but not in patients with RP. Despite deficits in cone density and ORG, visual sensitivity remained comparable to controls in three of four patients with RP. Conclusions: ORG-based measures of retinal dysfunction may precede deficits in cone structure and visual sensitivity. ORG is a sensitive measure of RP disease status and has significant potential to provide insight into disease progression and treatment efficacy.

PM2.5 constituents associated with mortality and kidney failure in childhood-onset lupus nephritis: A 19-year cohort study.

BACKGROUND: Childhood-onset lupus nephritis (cLN) is a severe form of systemic lupus erythematosus (SLE) with high morbidity and mortality. The impact of long-term exposure to fine particulate matter (PM2.5) on adverse outcomes in cLN remains unclear. METHODS: We combined a 19-years cLN cohort from seven provinces in China with high-resolution PM2.5 dataset from 2001 to 2020, investigating the association between long-term exposure to PM2.5 and its constituents (sulfate, nitrate, organic matter, black carbon, ammonium) with the risk of death and kidney failure, analyzed with multiple variables Cox models. We also evaluated the association between 3-year average PM2.5 exposure before study entry and baseline SLE disease activity index (SLEDAI) scores using linear regression models. RESULTS: Each 10 µg/m3 increase in annual average PM2.5 exposure was associated with an increased risk of death and kidney failure (HR = 1.58, 95 % CI: 1.24-2.02). Black carbon showed the strongest association (HR = 2.14, 95 % CI: 1.47-3.12). Higher 3-year average exposures to PM2.5 and its constituents were significantly associated with higher baseline SLEDAI scores. CONCLUSIONS: These findings highlight the significant role of environmental pollutants in cLN progression and emphasize the need for strategies to mitigate exposure to harmful PM2.5 constituents, particularly in vulnerable pediatric populations.

Learnable sparse dictionary compressed sensing for channeled spectropolarimeter.

Channeled spectropolarimetry enables real-time measurement of the polarimetric spectral information of the target. A crucial aspect of this technology is the accurate reconstruction of Stokes parameters spectra from the modulated spectra obtained through snapshot measurements. In this paper, a learnable sparse dictionary compressed sensing method is proposed for channeled spectropolarimeter (CSP) spectral reconstruction. Grounded in the compressive sensing framework, this method defines a variable sparse dictionary. It can learn prior knowledge from the measured modulated spectra, continuously optimizing its own structure and parameters iteratively by removing redundant basis functions and refining the matched basis functions. The learned sparse dictionary, post-training, can provide a more accurate sparse representation of the Stokes parameters spectra, enabling the proposed method to achieve more precise reconstruction results. To assess the efficacy of the proposed method, simulations and experiments were conducted, both of which consistently demonstrated the superior performance of the proposed approach. The suggested method is well-positioned to enhance the efficiency and accuracy of polarimetric spectral information retrieval in CSP applications.

Optimal exposure of mycophenolic acid for induction therapy of childhood lupus nephritis patients: an observational cohort study.

OBJECTIVES: Mycophenolic acid (MPA) is recommended for lupus nephritis (LN) treatment, but with large inter-individual variability in pharmacokinetics (PK). The aim of this study is to reveal the relationship between MPA exposure and disease response and adverse drug reactions in pediatric LN patients. METHOD: This was a population-based observational cohort study. A total of 86 pediatric LN patients treated with mycophenolate mofetil (MMF) for induction therapy were enrolled. The area-under the concentration-time curve (AUC) was calculated using MPA concentrations according to a limited sampling strategy. Receiver operating characteristic analysis was performed to assess the MPA-AUC threshold values. The cumulative incidence of renal remission and inactive systemic lupus erythematosus (SLE) over time was evaluated by Kaplan-Meier's analysis. RESULTS: MPA-AUC was identified as an independent factor associated with renal remission and lupus activity at 6 and 12 months after MMF treatment, and the improved renal remission rates were correlated with higher MPA-AUC, with thresholds of 29.81 and 30.63 µg·h·mL-1 at 6 months and 12 months, respectively. Furthermore, the thresholds for maintaining the hypoactive state of LN were 30.96 and 31.19 µg·h·mL-1at 6 months and 12 months, respectively. Patients reaching target thresholds for MPA-AUC achieved renal response or stable disease earlier. In addition, the MPA-AUC threshold for decreasing MMF-related adverse reactions was 50.80 µg·h·mL-1. CONCLUSION: The initial and long-term treatments of pediatric LN patients with MMF should be individualized according to the MPA-AUC, and the recommended MPA exposure is 31.19-50.80 µg·h·mL-1.

Early Rituximab as an Add-On Therapy in Children With the Initial Episode of Nephrotic Syndrome.

Introduction: The approximately 70% 12-month relapse in children experiencing the initial episode of steroid-sensitive nephrotic syndrome (SSNS) is a significant concern, with over 50% developing frequent relapses or steroid-dependent nephrotic syndrome (FRNS/SDNS). There is a lack of strategies to reduce relapse after the onset. Whether early administration of rituximab, which effectively reduces relapses in FRNS/SDNS, may be a solution has not been evaluated. Methods: A prospective, multicenter, open-label, single-arm trial was conducted in China, with a 12-month follow-up. Children aged 1 to 18 years with the first episode of nephrotic syndrome (NS) were screened for eligibility. Proteinuria was evaluated daily using dipsticks. A dose of 375 mg/m2 of rituximab was intravenously infused within 1 week after achieving corticosteroid-induced remission. The main outcome was 12-month relapse-free survival. Results: Out of the initially 66 children screened, 44 were enrolled and received rituximab, with all but 1 participant completing the 12-month follow-up. The median age at diagnosis was 4.3 years (interquartile range [IQR]: 3.4-5.9), and 33 (77%) of the participants were male. In the rituximab group, the 12-month relapse-free survival was significantly higher compared to historical controls (32 of 43 [74.4%] vs. 10 of 33 [30.3%]; P < 0.001; hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.80-7.81). The post hoc analysis revealed a higher 24-month relapse-free survival and a lower incidence of FRNS/SDNS at the 12-month follow-up. Treatment with rituximab was well-tolerated. Conclusion: Our findings support that early administration of rituximab may be associated with a higher 12-month relapse-free survival and a reduced incidence of FRNS/SDNS in children experiencing the initial episode of SSNS.

Trends and socioeconomic inequality of the burden of congenital abnormalities of the kidney and urinary tract among children and adolescents.

BACKGROUND: Although congenital abnormalities of the kidney and urinary tract (CAKUT) is the leading cause of childhood onset chronic kidney disease (CKD) and kidney failure, comprehensive information on the disease burden among children and adolescents globally is lacking. We aim to report the trends and socioeconomic inequality of CAKUT burden for people aged 0-24 years from 1990 to 2019·. METHODS: We reported the prevalence, mortality and disability-adjusted life-years (DALYs) for CAKUT based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, quantified the association of disease burden and socio-demographic index (SDI), calculated the slope index of inequality (SII) the relative index of inequality (RII) and concentration index. RESULTS: In 2019, the global prevalence, mortality, and DALYs of CAKUT among individuals aged 0-24 years were 167.11 (95%Confident Interval 166.97, 167.25), 0.30 (0.29, 0.30), and 32.22 (32.16, 32.29) per 100 000 population. The greatest prevalence, mortality and DALYs were recorded in the 0-4 year age group. The greatest mortality and DALYs were recorded in low SDI countries and territories. During 1990 to 2019, the prevalence, mortality and DALYs decreased globally, while in low and low-middle countries and territories the reduction was much less slower. India, Nigeria and Pakistan had the highest DALYs. Saudi Arabia and China exhibited a markedly decrease of CAKUT burden. Globally for every 0.1 increase in SDI, there was a 20.53% reduction in mortality, a 16.31% decrease in DALYs, but a 0.38% rise in prevalence. CONCLUSIONS: Inequality for disease burden of varying SDI was increasing globally. Thus, specific preventive and health service measures are needed to reduce the global burden from CAKUT.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism.

Renal interstitial fibrosis is an important mechanism in the progression of chronic kidney disease (CKD) to end-stage kidney disease. However, we lack specific treatments to slow or halt renal fibrosis. Ribosome profiling identified upregulation of a secreted micropeptide, C4orf48 (Cf48), in mouse diabetic nephropathy. Cf48 RNA and protein levels were upregulated in tubular epithelial cells in human and experimental CKD. Serum Cf48 levels were increased in human CKD and correlated with loss of kidney function, increasing CKD stage, and the degree of active interstitial fibrosis. Cf48 overexpression in mice accelerated renal fibrosis, while Cf48 gene deletion or knockdown by antisense oligonucleotides significantly reduced renal fibrosis in CKD models. In vitro, recombinant Cf48 (rCf48) enhanced TGF-ß1-induced fibrotic responses in renal fibroblasts and epithelial cells independently of Smad3 phosphorylation. Cellular uptake of Cf48 and its profibrotic response in fibroblasts operated via the transferrin receptor. RNA immunoprecipitation-sequencing identified Cf48 binding to mRNA of genes involved in the fibrotic response, including Serpine1, Acta2, Ccn2, and Col4a1. rCf48 binds to the 3'UTR of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis that operates as an RNA-binding peptide to promote the production of extracellular matrix.

Numerical simulation and fast method for the 0D-1D multi-scale coupled model and its application in ischemic brain tissue blood flow problems.

As living standards rise, more and more people are paying attention to their own health, especially issues such as cerebral thrombosis, cerebral infarction, and other cerebral blood flow problems. An accurate simulation of blood flow within cerebral vessels has emerged as a crucial area of research. In this study, we focus on microcirculatory blood flow in ischemic brain tissue and employ a 0D-1D geometric multi-scale coupled model to characterize this process. Given the intricate nature of human cerebral vessels, we apply a numerical method combining the finite element method and the third-order Runge-Kutta method to resolve the coupled model. To enhance computational efficiency, we introduce a fast method based on the reduced-order extrapolation algorithm. Our numerical example underscores the stability of the method and convergence accuracy to O h 3 + τ 3 , while significantly improving the accuracy and efficiency of blood flow simulation, making the mechanism analysis more accurate. Additionally, we present examples detailing variations and distribution of intracranial pressure and blood flow in ischemic brain tissue throughout a cardiac cycle. Both reduced vascular compliance and vascular stenosis can have adverse effects on intracranial cerebral pressure and blood flow, leading to insufficient local oxygen supply and negative effects on brain function. Meanwhile, there will also be corresponding changes in volume flow and pulsatile blood pressure.

(±)-Involucrasin D, a pair of enantiomeric bisflavonoid from the roots of Shuteria involucrata and its anti-inflammatory activity.

An undescribed bisflavonoid, named involucrasin D (1), along with two known flavonoids, 2(S)7,3',5'-trihydroxydihydroflavone (2) and sigmone (3) were isolated from the roots of Shuteria involucrata. A further chiral separation of 1 to yielded a pair of enantiomers (+)-1 and (-)-1. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Among them, bisflavonoid 1 and its enantiomers displayed remarkable anti-inflammatory effects by inhibiting the production of TNF-α and IL-6 in a dose-dependent manner.

Broadband light absorption by a hemispherical concentric nanoshell array.

Achieving highly efficient broadband absorption is an important research area in nanophotonics. In this paper, a novel method is proposed to design broadband near-perfect absorbers, consisting of a four-layer hemispherical concentric nanoshell array. The proposed nanostructure supports absorptivity exceeding 95% in the entire visible region, and the absorption bandwidth is determined by the interaction or 'hybridization' of the plasmons of the inner and outer metal-based nanoshells. Moreover, the designed absorber has wide-angle capability and is insensitive to polarization. The simple structure, as well as the stable absorption properties, suggests that such core-shell nanostructures can serve as a potential candidate for many applications such as solar energy harvesting, photo-detection, and emissivity control.

Risk factors and renal outcomes of AKI in children with secondary steroid-resistant nephrotic syndrome.

BACKGROUND: Acute kidney injury (AKI) is increasingly prevalent in children with nephrotic syndrome (NS). It is associated with adverse outcomes in NS, especially steroid-resistant nephrotic syndrome (SRNS). The incidence, risk factors and outcomes of AKI in secondary SRNS remain undefined. The main objectives of this study were to determine the risk factors and prognosis of AKI in hospitalized children with secondary SRNS. MATERIAL AND METHODS: This retrospective study was conducted from January 2014 to December 2019, involving 172 hospitalizations with secondary SRNS admitted to the First Affiliated Hospital of Sun Yat-sen University. AKI was defined and classified in accordance with the 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines. RESULTS: AKI was found in 67 (39.0%) of 172 hospitalizations with secondary SRNS. Average age of onset in our group is 4.4 (3.1, 6.7) years with AKI and 3.7 (1.8, 5.6) years without AKI. Urea nitrogen level is 5.9 (4.1, 10.0) mmol/L with AKI and 5.1 (3.7, 7.0) mmol/L. Uric acid level is 446.0 (340.0, 567.0) umol/L with AKI and 401.0 (303.0, 496.0) umol/L. 24-h urinary protein level is 4.14 (2.9, 6.5) g with AKI and 2.5 (1.3, 5.3) without AKI. Multivariate logistic regression revealed that infection (OR = 5.287; 95% confidence interval, 2.349 to 11.899; p < 0.001), age at onset (OR = 1.180; 95% confidence interval, 1.032 to 1.349; p = 0.015) and uric acid level (OR = 1.003; 95% confidence interval, 1.000 to 1.006; p = 0.031) were significantly associated with the development of AKI in children with secondary SRNS. Among 72 children with secondary SRNS, six went to end-stage kidney disease (ESKD). Children in the AKI group were more likely to progress to ESKD compared with children in the non-AKI group (p = 0.017) with a median follow-up of 48.5months. CONCLUSION: AKI occurred in 39.0% of total hospitalizations associated with secondary SRNS. Risk factors including infection, age of onset, and uric acid level are associated with AKI in children with secondary SRNS. Furthermore, AKI was identified as a risk factor for the progression of secondary SRNS to ESKD.

Single-cell profiling reveals kidney CD163+ dendritic cell participation in human lupus nephritis.

OBJECTIVES: The current work aimed to provide a comprehensive single-cell landscape of lupus nephritis (LN) kidneys, including immune and non-immune cells, identify disease-associated cell populations and unravel their participation within the kidney microenvironment. METHODS: Single-cell RNA and T cell receptor sequencing were performed on renal biopsy tissues from 40 patients with LN and 6 healthy donors as controls. Matched peripheral blood samples from seven LN patients were also sequenced. Multiplex immunohistochemical analysis was performed on an independent cohort of 60 patients and validated using flow cytometric characterisation of human kidney tissues and in vitro assays. RESULTS: We uncovered a notable enrichment of CD163+ dendritic cells (DC3s) in LN kidneys, which exhibited a positive correlation with the severity of LN. In contrast to their counterparts in blood, DC3s in LN kidney displayed activated and highly proinflammatory phenotype. DC3s showed strong interactions with CD4+ T cells, contributing to intrarenal T cell clonal expansion, activation of CD4+ effector T cell and polarisation towards Th1/Th17. Injured proximal tubular epithelial cells (iPTECs) may orchestrate DC3 activation, adhesion and recruitment within the LN kidneys. In cultures, blood DC3s treated with iPTECs acquired distinct capabilities to polarise Th1/Th17 cells. Remarkably, the enumeration of kidney DC3s might be a potential biomarker for induction treatment response in LN patients. CONCLUSION: The intricate interplay involving DC3s, T cells and tubular epithelial cells within kidneys may substantially contribute to LN pathogenesis. The enumeration of renal DC3 holds potential as a valuable stratification feature for guiding LN patient treatment decisions in clinical practice.

Economic burden attributable to healthcare-associated infections at western China hospitals: 6 Year, prospective cohort study.

OBJECTIVES: Healthcare-associated infections (HAIs) represent a major threat to patient safety and are associated with significant economic burden. Calculating the costs attributable to HAIs is challenging given the various sources of bias. Although HAIs as a reasonably preventable medical harm should have been closely linked to medical insurance incentives, there was little linkage between HAIs and medicare in western China owing to the lack of economic evaluation data. The present study aimed to generate estimates of the attributable costs associated with HAIs and the magnitude of costs growth. METHODS: In this cohort study designed horizontally and vertically from 2016 to 2022, we compared outcomes of randomly sampling patients with HAIs and individually matched patients without HAIs in two cohorts at a 6-year interval at 34 hospitals in western China. The primary outcome was the direct medical cost for the entire hospital stay, converted to US dollars ($ for the benchmark year), discounted at 3% annually, and estimated separately in the full analysis set (FAS) and the per protocol set (PPS). We used multiple linear regression to adjust the discounted costs and to assess subgroups effects within each cohort. We nested a dynamic vertical comparison of costs attributable to HAIs between the front and rear cohorts. RESULTS: A total of 230 patients with HAIs in 2016 and 204 patients with HAIs in 2022 were enrolled. After a 1:1 match, all 431 pairs were recruited as FAS, of which 332 pairs as PPS met all matching restrictions. Compared to the 2016 cohort in FAS, the patients with HAIs in 2022 had a significantly older age (64.40 ± 16.45 years), higher repeat hospitalization rate (65 [32.02%] of 203), and lower immune function (69 [33.99%] of 203). The discounted costs and adjusted-discounted costs for patients with HAIs in the 2022 cohort were found to be significantly higher than those of patients without HAIs (discounted costs: $5484.60 [IQR 8426.03] vs $2554.04(4530.82), P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3040.21(1823.36), P < 0.001, respectively), and also higher than those of patients with HAIs in the 2016 cohort (discounted costs: $5484.60 [8426.03] vs $3553.00 [6127.79], P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3703.82 [3159.14], P < 0.001, respectively). In vertical comparison of PPS, the incremental costs of the 2022 cohort are 1.48 times higher than those of the 2016 cohort ($964.63(4076.15) vs $652.43 [2533.44], P = 0.084). CONCLUSIONS: This meticulously designed study in western China has successfully and accurately examined the economic burden attributable to HAIs. Their rapidly increasing tendency poses a serious challenge to patients, hospitals, and the medical insurance. A closer linkage between HAIs and ongoing motivating system changes is urgently needed in western China.

LncRNA KCNQ1OT1/miR-496/HMGB1 Signaling Axis Promotes Invasion and Migration of Non-small Cell Lung Cancer Cells.

Enhanced invasion and migration of non-small cell lung cancer (NSCLC) cells is the major cause of metastasis and poor prognosis in NSCLC. This study was conducted to investigate the role and mechanism of lncRNA KCNQ1OT1 in the proliferation, invasion, and migration of NSCLC cells. The expression of KCNQ1OT1 in NSCLC was analyzed in the StarBase database, and the target miRNA of KCNQ1OT1 as well as the target genes of the miRNA was predicted. Then, the mRNA expression levels of KCNQ1OT1, miR-496, and HMGB1 were detected in clinical tissue samples and cells by qRT-PCR assay. Besides, the protein levels of HMGB1 were detected by Western blot. MTT assay, transwell assay, and scratch assay were used to determine the proliferation, invasion, and migration ability of NSCLC cells, respectively. Correlation analysis was performed to assess the correlation between the expression of KCNQ1OT1, miR-496, and HMGB1 in clinical NSCLC samples. Dual-luciferase reporter gene assay was conducted to analyze the interaction between KCNQ1OT1 and miR-496 and between miR-496 and HMGB1. The database results showed that KCNQ1OT1 was highly expressed in NSCLC. Similarly, we found that the expression level of KCNQ1OT1 was significantly higher in NSCLC tissues and cells than that in the corresponding normal tissues and cells. The results of MTT assay, transwell assay, and scratch assay demonstrated that KCNQ1OT1 significantly enhanced the proliferation, invasion, and migration of NSCLC cells. Further mechanism exploration revealed that KCNQ1OT1 could sponge miR-496, and miR-496 directly targeted and regulated the expression of HMGB1. The expression of miR-496 and either KCNQ1OT1 or HMGB1 were negatively correlated in NSCLC, while the expression of KCNQ1OT1 and HMGB1 were positively correlated. Compared with normal paracancer tissues, miR-496 was much lower and HMGB1 was much higher expressed in NSCLC tissues. The results of cotransfection also further demonstrated that miR-496 inhibitor or sh-HMGB1 cotransfected with sh-KCNQ1OT1 could significantly decrease or increase the ability of sh-KCNQ1OT1 to inhibit the proliferation, invasion, and migration of H1299 cells, respectively. In conclusion, lncRNA KCNQ1OT1 promotes the invasion and migration of NSCLC cells through miR-496/HMGB1 signaling axis.

Impact of using peer role-playing on the clinical skills performance of pediatric trainees.

OBJECTIVE: The aim of this study was to evaluate the impact of peer role-playing on the clinical skills performance of pediatric trainees. METHODS: Seventy-eight clinical medicine trainees were randomly divided into a role-playing group and a traditional teaching group, with 39 students in each group. The role-playing group alternated between the roles of clinicians and patients, while the traditional teaching group received the bedside teaching mode of verbal instruction. After two weeks traineeship, mini-Clinical Evaluation Exercise(Mini-CEX) was used to evaluate the trainees' competence in physician-patient communication and clinical practice. A questionnaire was given to the role-playing group to assess their satisfaction with the method. RESULTS: The Mini-CEX scores showed that the role-playing group had superior clinical skills (p < 0.05), including communication, history taking, professionalism, organization, clinical skills, and physical examination, compared to the traditional teaching group. Furthermore, trainee satisfaction was high with the role-playing method,and the satisfaction were more than 95%. CONCLUSION: The role-playing method effectively improved the clinical skills of pediatric trainees, developed clinical communication skills, and enhanced the application of medical knowledge in a simulated medical environment.

PEGA-BA@Ce6@PFCE Micelles as Oxygen Nanoshuttles for Tumor Hypoxia Relief and Enhanced Photodynamic Therapy.

Tumor hypoxia, which is mainly caused by the inefficient microvascular systems induced by rapid tumor growth, is a common characteristic of most solid tumors and has been found to hinder treatment outcomes for many types of cancer therapeutics. In this study, an amphiphilic block copolymer, poly (ethylene glycol) methyl ether acrylate-block-n-butyl acrylate (PEGA-BA), was prepared via the ATRP method and self-assembled into core-shell micelles as nano radiosensitizers. These micelles encapsulated a photosensitizer, Chlorin e6 (Ce6), and demonstrated well-defined morphology, a uniform size distribution, and high oxygen loading capacity. Cell experiments showed that PEGA-BA@Ce6@PFCE micelles could effectively enter cells. Further in vitro anticancer studies demonstrated that the PEGA-BA@Ce6@PFCE micelles significantly suppressed the tumor cell survival rate when exposed to a laser.

Th1-polarized MtrE-based gonococcal vaccines display prophylactic and therapeutic efficacy.

ABSTRACTGlobal dissemination of high-level ceftriaxone-resistant Neisseria gonorrhoeae strains associated with the FC428 clone poses a threat to the efficacy ceftriaxone-based therapies. Vaccination is the best strategy to contain multidrug-resistant infections. In this study, we investigated the efficacy of MtrE and its surface Loop2 as vaccine antigens when combined with a Th1-polarizing adjuvant, which is expected to be beneficial for gonococcal vaccine development. Using in vitro dendritic cell maturation and T cell differentiation assays, CpG1826 was identified as the optimal Th1-polarizing adjuvant for MtrE and Loop2 displayed as linear epitope (Nloop2) or structural epitope (Intraloop2) on a carrier protein. Loop2-based antigens raised strongly Th1-polarized and bactericidal antibody responses in vaccinated mice. Furthermore, the vaccine formulations provided protection against a gonococcal challenge in mouse vaginal tract infection model when provided as prophylactic vaccines. Also, the vaccine formulations accelerated gonococcal clearance when provided as a single therapeutic dose to treat an already established infection, including against a strain associated with the FC428 clone. Therefore, this study demonstrated that MtrE and Loop 2 are effective gonococcal vaccine antigens when combined with the Th1-polarizing CpG1826 adjuvant.

Misdiagnosed Branchio-Oto-Renal syndrome presenting as proteinuria and renal insufficiency with insidious signs since early childhood: a report of three cases.

BACKGROUND: Branchio-oto-renal (BOR) syndrome is an inherited multi-systemic disorder. Auricular and branchial signs are highly suggestive of BOR syndrome but often develop insidiously, leading to a remarkable misdiagnosis rate. Unlike severe morphological abnormalities of kidneys, knowledge of glomerular involvement in BOR syndrome were limited. CASE PRESENTATION: Three cases, aged 8 ~ 9 years, visited pediatric nephrology department mainly for proteinuria and renal insufficiency, with 24-h proteinuria of 23.8 ~ 68.9 mg/kg and estimated glomerular filtration rate of 8.9 ~ 36.0 mL/min/1.73m2. Moderate-to-severe albuminuria was detected in case 1, while mixed proteinuria was detected in case 2 and 3. Insidious auricular and branchial fistulas were noticed, all developing since early childhood but being neglected previously. EYA1 variants were confirmed by genetic testing in all cases. Delay in diagnosis was 8 ~ 9 years since extra-renal appearances, and 0 ~ 6 years since renal abnormalities. In case 1, therapy of glucocorticoid and immunosuppressive agents to accompanying immune-complex mediated glomerulonephritis was unsatisfying. CONCLUSIONS: BOR syndrome is a rare cause of proteinuria and abnormal kidney function and easily missed, thus requiring more awareness. Careful medical history taking and physical examination are essential to early diagnosis. Massive proteinuria was occasionally seen in BOR syndrome, which might be related to immune complex deposits. A novel pathogenic variant (NM_000503.6 (EYA1): c.1171delT p.Ser391fs*9) was firstly reported.