IL-33 regulates adipogenesis via Wnt/ß-catenin/PPAR-γ signaling pathway in preadipocytes.

Interleukin-33 (IL-33), an emerging cytokine within the IL-1 family, assumes a pivotal function in the control of obesity. However, the specific mechanism of its regulation of obesity formation remains unclear. In this study, we found that the expression level of IL-33 increased in visceral adipose tissue in mice fed with a high-fat diet (HFD) compared with that in mice fed with a normal diet (ND). In vitro, we also found the expression level of IL-33 was upregulated during the adipogenesis of 3T3-L1 cells. Functional test results showed that knockdown of IL-33 in 3T3-L1 cells differentiation could promote the accumulation of lipid droplets, the content of triglyceride and the expression of adipogenic-related genes (i.e. PPAR-γ, C/EBPα, FABP4, LPL, Adipoq and CD36). In contrast, overexpression of IL-33 inhibits adipogenic differentiation. Meanwhile, the above tests were repeated after over-differentiation of 3T3-L1 cells induced by oleic acid, and the results showed that IL-33 played a more significant role in the regulation of adipogenesis. To explore the mechanism, transcriptome sequencing was performed and results showed that IL-33 regulated the PPAR signaling pathway in 3T3-L1 cells. Further, Western blot and confocal microscopy showed that the inhibition of IL-33 could promote PPAR-γ expression by inhibiting the Wnt/ß-catenin signal in 3T3-L1 cells. This study demonstrated that IL-33 was an important regulator of preadipocyte differentiation and inhibited adipogenesis by regulating the Wnt/ß-catenin/PPAR-γ signaling pathway, which provided a new insight for further research on IL-33 as a new intervention target for metabolic disorders.

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.

Mitochondrial micropeptide MOXI promotes fibrotic gene transcription by translocation to the nucleus and bridging N-acetyltransferase 14 with transcription factor c-Jun.

Progressive fibrosis is a hallmark of chronic kidney disease, but we lack effective treatments to halt this destructive process. Micropeptides (peptides of no more than 100 amino acids) encoded by small open reading frames represent a new class of eukaryotic regulators. Here, we describe that the micropeptide regulator of ß-oxidation (MOXI) regulates kidney fibrosis. MOXI expression was found to be up-regulated in human fibrotic kidney disease, and this correlated with the degree of fibrosis and loss of kidney function. MOXI was expressed in the cytoplasm and mitochondria of cultured tubular epithelial cells and translocated to the nucleus upon Transforming Growth Factor-ß1 stimulation. Deletion of Moxi protected mice against fibrosis and inflammation in the folic acid and unilateral ureteral obstruction models. As a potential molecular therapy, treatment with an antisense MOXI oligonucleotide effectively knocked-down MOXI expression and protected against kidney fibrosis in both models. Bimolecular fluorescence complementation identified the enzyme N-acetyltransferase 14 (Nat14) and transcription factor c-Jun as MOXI binding partners. The MOXI/Nat14/c-Jun complex enhances basal and Transforming Growth Factor-ß1 induced collagen I gene promoter activity. Phosphorylation at T49 is required for MOXI nuclear localization and for complex formation with Nat14 and c-Jun. Furthermore, mice with a MoxiT49A point mutation were protected in the models of kidney fibrosis. Thus, our studies demonstrate a key role for the micropeptide MOXI in kidney fibrosis and identify a new function of MOXI in forming a transcriptional complex with Nat14 and c-Jun.

Ultrasensitive Self-Driven Terahertz Photodetectors Based on Low-Energy Type-II Dirac Fermions and Related Van der Waals Heterojunctions.

The exotic electronic properties of topological semimetals (TSs) have opened new pathways for innovative photonic and optoelectronic devices, especially in the highly pursuit terahertz (THz) band. However, in most cases Dirac fermions lay far above or below the Fermi level, thus hindering their successful exploitation for the low-energy photonics. Here, low-energy type-II Dirac fermions in kitkaite (NiTeSe) for ultrasensitive THz detection through metal-topological semimetal-metal heterostructures are exploited. Furthermore, a heterostructure combining two Dirac materials, namely, graphene and NiTeSe, is implemented for a novel photodetector exhibiting a responsivity as high as 1.22 A W-1 , with a response time of 0.6 µs, a noise-equivalent power of 18 pW Hz-0.5 , with outstanding stability in the ambient conditions. This work brings to fruition of Dirac fermiology in THz technology, enabling self-powered, low-power, room-temperature, and ultrafast THz detection.

Incidence of relapse and frequently relapsing/steroid-dependent nephrotic syndrome in Chinese children with steroid-sensitive nephrotic syndrome: A cohort study.

AIM: This study aimed to investigate the incidence of relapse and FR/SDNS in Chinese children with SSNS and to develop clinical prediction models for relapse and FR/SDNS. METHODS: This retrospective cohort study involved 339 newly onset SSNS patients between 2006 and 2016. The incidence of relapse and FR/SDNS were estimated using the Kaplan-Meier method. Prediction models were constructed based on Cox proportional-hazards regression. RESULTS: The median follow-up time was 8.7 years. The cumulative incidence of relapse at 1-, 2-, and 5-year was 51.0%, 62.5%, and 66.6%. The cumulative incidence of FR/SDNS at 1-, 2-, and 5-year was 18.4%, 29.0%, and 32.9%. The final prediction model for first relapse included four variables (serum albumin, triglycerides, IgM, and time to first remission). The model's discriminative ability was low (Harrell's C index = 0.62). The final prediction model for FR/SDNS included four variables (serum albumin, lipoprotein(a), time to first remission, and time to first relapse). The discrimination and calibration of the prediction model for FR/SDNS were acceptable (Harrell's C index = 0.73, Brier score at 1- and 2-year were 0.11 and 0.17). CONCLUSION: The first relapse and FR/SDNS mainly occurred in the first 2 years after initial SSNS onset. The prediction model for relapse developed using common clinical parameters performed poorly, while the prediction model for FR/SDNS might be useful.

Attachment style and attention bias to emotional information: The moderating effect of stress, stimulus characteristics, and attention stage.

OBJECTIVE: We examined whether insecurely attached individuals exhibit an attention bias to emotional information, and further tested the potential moderating role of stress, information valence, information attachment relevance, and attention stage. BACKGROUND: Attachment style can predict people's attention to emotional information. However, the empirical findings are inconsistent, making it difficult to determine the associations between attachment style and attention bias to emotional information. METHOD: We included 68 studies (N = 5417) across 46 published and unpublished articles (the initial pool was 627 articles) in the meta-analysis. RESULTS: People high on attachment avoidance exhibited decreased attention toward emotional stimuli (d = -0.129, p = 0.020), which was not affected by stress, information valence, information attachment relevance, or attention stage. Conversely, people high on attachment anxiety exhibited increased attention toward emotional stimuli, especially under stress, if the information was attachment-related, and during late-stage attentional processing. They exhibited an early bias away from and a late bias toward emotional information, which was intensified under stress. CONCLUSION: Our findings support the proposition that people high on attachment avoidance use deactivating strategies in attentional processing; whereas people high on attachment anxiety use hyperactivating strategies, especially when resources are limited (under stress). When resources are available, and it is relatively early in the process, people high on attachment anxiety respond similarly to those high on attachment avoidance.

Monolayer Graphene Terahertz Detector Integrated with Artificial Microstructure.

Graphene, known for its high carrier mobility and broad spectral response range, has proven to be a promising material in photodetection applications. However, its high dark current has limited its application as a high-sensitivity photodetector at room temperature, particularly for the detection of low-energy photons. Our research proposes a new approach for overcoming this challenge by designing lattice antennas with an asymmetric structure for use in combination with high-quality monolayers of graphene. This configuration is capable of sensitive detection of low-energy photons. The results show that the graphene terahertz detector-based microstructure antenna has a responsivity of 29 V·W-1 at 0.12 THz, a fast response time of 7 µs, and a noise equivalent power of less than 8.5 pW/Hz1/2. These results provide a new strategy for the development of graphene array-based room-temperature terahertz photodetectors.

Boosting attachment security promotes prosociality: The mediating effect of moral disengagement.

While attachment security is known to promote prosocial behaviour, a closer examination is needed to clarify the active mechanism in this relationship. We addressed this issue by examining the mediation effect of moral disengagement in two studies. Participants were assigned to the control priming group or the attachment security priming group. After the priming procedure, they completed the measurements of a sense of security, moral disengagement and prosocial behaviour. The results from both studies showed that compared with control priming, attachment security priming enhanced prosociality. Furthermore, mediation analysis showed that moral disengagement mediated the relationship between attachment security and prosociality. The present findings extend the understanding of the underlying mechanisms of attachment security and prosociality, and provide insights into the effectiveness of boosting attachment security in intervening in moral disengagement.

Application of adrenocorticotropic hormone in recurrent focal segmental glomerulosclerosis post-transplantation: A case report and literature review.

BACKGROUND: The recurrence rate of focal segmental glomerulosclerosis (FSGS) post-renal transplantation is as high as 30%-50%. However, the pathogenesis is unclear. At present, there is no unified standard for the treatment of recurrent FSGS post-transplantation. Its treatment is full of risks and challenges. METHODS: We report a child with recurrent FSGS with massive proteinuria 6~9 g/m2 /day and resistance to plasma exchange (PE) and rituximab (RTX). On the basis of receiving anti-rejection therapy of prednisone, tacrolimus, and mycophenolate mofetil (MMF), we treated the child with adrenocorticotropic hormone (ACTH), and reviewed the literature on the application of ACTH in the recurrence of FSGS post-transplantation. RESULTS: After 1 year of treatment with ACTH, the patient's urinary protein decreased and fluctuated between 0.6 and 1.1 g/m2 /day. The albumin (ALB) and cholesterol (CHOL) returned to the normal range. The patient achieved complete remission after 19 months of ACTH treatment and maintained until now. There was no obvious adverse reaction. Literature review showed that up to February 2021, a total of 8 studies showed the use of ACTH in kidney transplant patients, and all the patients in the study achieved remission. CONCLUSIONS: ACTH is a potential option for treating recurrent FSGS post-transplantation with fewer side effects and relatively safe for patients. However, further evaluation is needed to better adapt to different populations.

Dyslipidemia may be a risk factor for progression in children with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is often chronically progressive and commonly accompanied by dyslipidemia. However, the intrinsic relationship between dyslipidemia and IgAN remains to be elucidated. This study aimed to investigate the impact of different types of dyslipidemia on clinical and pathological characteristics in children with IgAN. METHODS: In our retrospective cohort study from January 2006 to January 2021, 276 children with IgAN were ultimately included in the baseline analysis, and 169 were included in the follow-up analysis. The clinical and pathological features of different types of dyslipidemia and their effect on kidney prognosis were analyzed. RESULTS: Children in the dyslipidemia group had more severe clinical characteristics (higher blood urea nitrogen, serum uric acid, and 24-h proteinuria; higher proportion of hypertension; and lower serum albumin and estimated glomerular filtration rate) and pathological changes (higher proportion of Lee grades IV-V and E1, S1, and C2 in MEST-C). Furthermore, the clinical and pathological characteristics were worse in the mixed hyperlipidemia group. Multivariate logistic analysis showed that hypertension, steroid treatment, lower serum albumin, severe proteinuria, and segmental glomerulosclerosis were independent risk factors for dyslipidemia in children with IgAN. The Kaplan-Meier analysis revealed that the probability of kidney survival in children with dyslipidemia was lower than that in those without dyslipidemia, with a median follow-up of 5.9 years. CONCLUSIONS: Children with IgAN and dyslipidemia, especially mixed hyperlipidemia, are prone to more severe clinical and pathological changes. Our study provides further insight into dyslipidemia as a potential risk factor in children with IgAN. A higher resolution version of the Graphical abstract is available as Supplementary information.

Small Foreign Object Debris Detection for Millimeter-Wave Radar Based on Power Spectrum Features.

Foreign object debris (FOD) detection can be considered a kind of classification that distinguishes the measured signal as either containing FOD targets or only corresponding to ground clutter. In this paper, we propose a support vector domain description (SVDD) classifier with the particle swarm optimization (PSO) algorithm for FOD detection. The echo features of FOD and ground clutter received by the millimeter-wave radar are first extracted in the power spectrum domain as input eigenvectors of the classifier, followed with the parameters optimized by the PSO algorithm, and lastly, a PSO-SVDD classifier is established. However, since only ground clutter samples are utilized to train the SVDD classifier, overfitting inevitably occurs. Thus, a small number of samples with FOD are added in the training stage to further construct a PSO-NSVDD (NSVDD: SVDD with negative examples) classifier to achieve better classification performance. Experimental results based on measured data showed that the proposed methods could not only achieve a good detection performance but also significantly reduce the false alarm rate.

Oocyte-dependent activation of MTOR in cumulus cells controls the development and survival of cumulus-oocyte complexes.

Communication between oocytes and their companion somatic cells promotes the healthy development of ovarian follicles, which is crucial for producing oocytes that can be fertilized and are competent to support embryogenesis. However, how oocyte-derived signaling regulates these essential processes remains largely undefined. Here, we demonstrate that oocyte-derived paracrine factors, particularly GDF9 and GDF9-BMP15 heterodimer, promote the development and survival of cumulus-cell-oocyte complexes (COCs), partly by suppressing the expression of Ddit4l, a negative regulator of MTOR, and enabling the activation of MTOR signaling in cumulus cells. Cumulus cells expressed less Ddit4l mRNA and protein than mural granulosa cells, which is in striking contrast to the expression of phosphorylated RPS6 (a major downstream effector of MTOR). Knockdown of Ddit4l activated MTOR signaling in cumulus cells, whereas inhibition of MTOR in COCs compromised oocyte developmental competence and cumulus cell survival, with the latter likely to be attributable to specific changes in a subset of transcripts in the transcriptome of COCs. Therefore, oocyte suppression of Ddit4l expression allows for MTOR activation in cumulus cells, and this oocyte-dependent activation of MTOR signaling in cumulus cells controls the development and survival of COCs.

Diffusion kurtosis MRI versus conventional diffusion-weighted imaging for evaluating inflammatory activity in Crohn's disease.

PURPOSE: To assess the efficacy of diffusion kurtosis imaging (DKI) and to compare DKI-derived parameters with that of conventional diffusion-weighted imaging (DWI) for grading the inflammatory activity of Crohn's disease (CD). MATERIALS AND METHODS: In all, 38 patients with CD underwent 3T magnetic resonance enterography (MRE) with DKI (b values of 0-2000 s/mm2 ). The inflammatory activity of the bowel segments was graded by magnetic resonance index of activity (MaRIA) as inactive (<7), mild (≥7 and <11), or moderate-severe (≥11). Apparent diffusion for non-Gaussian distribution (Dapp ) and apparent kurtosis coefficient (Kapp ) on DKI as well as apparent diffusion coefficient (ADC) on DWI were compared. RESULTS: In all, 86 bowel segments including inactive (20), mild (19), and moderate-severe (47) CD were analyzed. The differences in Kapp , Dapp , and ADC among inactive, mild, and moderate-severe CD were significant (all P < 0.05). Kapp (r = 0.862), Dapp (r = -0.755), and ADC (r = -0.713) correlated well with MaRIA in all segments. Stronger correlation with MaRIA in moderate-severe CD was found for Kapp (r = 0.647) than that of Dapp (r = -0.414) and ADC (r = -0.580). Receiver operating characteristic (ROC) curve analysis showed high accuracy of Kapp , Dapp , and ADC for differentiating active from inactive CD (AUC: 0.953 for Kapp , 0.944 for Dapp , 0.907 for ADC) as well as differentiating inactive-mild from moderate-severe CD (AUC: 0.946 for Kapp , 0.887 for Dapp , 0.846 for ADC). The threshold Kapp of 0.731 allowed differentiation of active from inactive CD with 89.4% sensitivity and 95% specificity. CONCLUSION: DKI of CD is clinically feasible and might be superior to conventional DWI for grading the inflammatory activity of CD. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:702-709.

T2* Mapping to characterize intestinal fibrosis in crohn's disease.

BACKGROUND: Assessing bowel fibrosis in patients with Crohn's disease (CD) has important therapeutic implications. PURPOSE: To determine the utility of T2* mapping versus that of contrast enhanced (CE) imaging in grading intestinal fibrosis in patients with CD using surgical pathology as the reference standard. STUDY TYPE: Prospective. SPECIMENS: 102 specimens from 27 patients with CD. FIELD STRENGTH/SEQUENCE: 3.0T; T2WI; T1WI; T2*WI. ASSESSMENT: The T2*WI values of the bowel wall targeted for resection were measured by two radiologists by drawing regions of interest on the thickened bowel wall. The resected bowel specimens with pathological fibrosis and type I collagen were classified into four severity grades (0-3) by a pathologist using a semi-quantitative scoring system. STATISTICAL TESTS: The differences in the T2*WI values among the different histological grades were analyzed using one-way analysis of variance or the Kruskal-Wallis test, and their correlations were analyzed. The ability of the T2*WI values to discriminate between various degrees of fibrosis was assessed using a receiver operating characteristic (ROC) curve. RESULTS: Significant differences were observed in the T2* values of mild (23.56 ± 1.60 ms), moderate (16.19 ± 0.55 ms), and severe (13.59 ± 0.53 ms) fibrosis types (F = 35.84; P < 0.001). T2* values were moderately associated with histological fibrosis (r = -0.627; P < 0.001) and type I collagen scores (r = -0.588; P < 0.001). T2* values were highly accurate, with an area under the ROC curve (AUC) of 0.951 (P < 0.001) for differentiating moderate-to-severe fibrosis from nonfibrosis and mild fibrosis, followed by an AUC of 0.508 for the percentage of enhancement gain (P = 0.908). A threshold T2* value of 18.06 ms was recommended for diagnosing moderate-to-severe fibrosis with 94.7% sensitivity and 78.3% specificity. DATA CONCLUSION: MRI T2* mapping outperforms CE parameters in distinction of various degrees of bowel fibrosis in CD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Real-world impact of non-breast cancer-specific death on overall survival in resectable breast cancer.

BACKGROUND: The real-world occurrence rate of non-breast cancer-specific death (non-BCSD) and its impact on patients with breast cancer are poorly recognized. METHODS: Women with resectable breast cancer from 1990 to 2007 in the Surveillance, Epidemiology, and End Results database (n = 199,963) were analyzed. The outcome events of breast cancer were classified as breast cancer-specific death (BCSD), non-BCSD, or survival. Binary logistics was used to estimate the occurrence rates of non-BCSD and BCSD with different clinicopathological factors. The Gray method was used to measure the cumulative incidence of non-BCSD and BCSD. The ratio of non-BCSDs to all causes of death and stacked cumulative incidence function plots were used to present the impact of non-BCSD on overall survival (OS). Models of Cox proportional hazards regression and competing risk regression were compared to highlight the suitable model. RESULTS: There were 12,879 non-BCSDs (6.44%) and 28,784 BCSDs (14.39%). The oldest age group (>62 years), black race, and a single or divorced marital status were associated with more non-BCSDs. With adjustments for age, a hormone receptor-positive (HoR+) status was no longer related to increased non-BCSDs. In patients with grade 1, stage I disease and an HoR+ status as well as the oldest subgroup, a great dilution of non-BCSD on all causes of death could be observed, and this led to incorrect interpretations. The inaccuracy, caused by the commonly used Cox proportional hazards model, could be corrected by a competing risk model. CONCLUSIONS: OS was largely impaired by non-BCSD during early breast cancer. For some future clinical trial planning, especially for the oldest patients and those with HoR+ breast cancer, non-BCSD should be considered a competing risk event. Cancer 2017;123:2432-43. © 2017 American Cancer Society.

Gd-EOB-DTPA-enhanced magnetic resonance imaging combined with T1 mapping predicts the degree of differentiation in hepatocellular carcinoma.

BACKGROUND: Variable degrees of differentiation in hepatocellular carcinoma(HCC)under Edmondson-Steiner grading system has been proven to be an independent prognostic indicator for HCC. Up till now, there has been no effective radiological method that can reveal the degree of differentiation in HCC before surgery. This paper aims to evaluate the use of Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging combined with T1 mapping for the diagnosis of HCC and assessing its degree of differentiation. METHODS: Forty-four patients with 53 pathologically proven HCC had undergone Gd-EOB-DTPA enhanced MRI with T1 mapping before surgery. Out of the 53 lesions,13 were grade I, 27 were gradeII, and 13 were grade III. The T1 values of each lesion were measured before and at 20 min after Gd-EOB-DTPA administration (T1p and T1e). The absolute reduction in T1 value (T1d) and the percentage reduction (T1d %) were calculated. The one-way ANOVA and Pearson correlation were used for comparisons between the T1 mapping values. RESULTS: The T1d and T1d % of grade I, II and III of HCC was 660.5 ± 422.8ms、295.0 ± 99.6ms、276.2 ± 95.0ms and 54.0 ± 12.2 %、31.5 ± 6.9 %、27.7 ± 6.7 % respectively. The differences between grade Iand II, grade Iand III were statistically significant (p < 0.05), but there was no statically significant difference between grade II and III. The T1d % was the best marker for grading of HCC, with a Spearman correlation coefficient of -0.676. CONCLUSIONS: T1 mapping before and after Gd-EOB-DTPA administration can predict degree of differentiation in HCC.

Signet ring cell carcinoma of resectable metastatic colorectal cancer has rare surgical value.

BACKGROUND AND OBJECTIVES: Signet ring cell carcinoma (SRCC) is a uniquely separated subgroup in metastatic colorectal cancer (mCRC). The aims are to investigate the value of resection in patients with resectable metastatic signet ring cell colorectal cancer. METHODS: Patients with mCRC who underwent resection in Surveillance, Epidemiology, and End Results database during 1998-2010 were retrospectively analyzed. Kaplan-Meier and COX models were used to analyze the differences in the survival. Logistic regression models were used to evaluate the relationship between SRCC and other clinicopathological factors. RESULTS: Among the 3,568 patients, 94 (2.63%) patients had SRCC. The median survival time of patients with SRCC and non-SRCC were 17 and 29 months, respectively (P < 0.001). Multivariate analysis indicated that SRCC was an independent prognostic factor for poor overall survival. Logistic regression model based on variables identified by univariate analysis indicated that younger age (≤50 years old) (P = 0.005), female (P < 0.001), location in colon (P = 0.012), and N positive status (P = 0.003) were independent variables correlated with the SRCC subgroup. SRCC had a dramatically higher invalid surgical outcome rate than non-SRCC (P = 0.001). CONCLUSION: SRCC patients might benefit little from the resection of primary and metastatic lesions with a high rate of undergoing invalid operations. J. Surg. Oncol. 2016;114:1004-1008. © 2016 Wiley Periodicals, Inc.

Plasma levels of oxidative stress in children with steroid-sensitive nephrotic syndrome and their predictive value for relapse frequency.

BACKGROUND: Oxidative stress has been reported to play an important role in children with primary nephrotic syndrome (PNS). However, the results of previous studies are controversial. METHODS: Forty children with steroid-sensitive nephrotic syndrome (SSNS) and 20 age- and sex-matched healthy controls were enrolled. Patients were followed-up for 12-18 months and divided into three subgroups: frequent relapse (n = 10), non-frequent relapse (n = 12), and non-relapse (n = 18). The plasma levels of advanced oxidation protein products (AOPP), malondialdehyde (MDA), and superoxide dismutase (SOD) were tested in controls and patient group at first presentation and after 4 weeks of steroid treatment. RESULTS: Patients had higher AOPP and MDA levels but lower SOD compared with controls. AOPP levels were significantly higher in the frequent relapse subgroup compared with the non-frequent relapse and non-relapse subgroups, respectively. No significant differences were found in the plasma levels of MDA and SOD among the three subgroups. AOPP >87.55 µmol/l before steroid treatment and AOPP >78.5 µmol/l after 4-week steroid treatment were positively correlated with the relapse frequency in patients with SSNS. CONCLUSIONS: Children with SSNS have oxidative stress. The plasma levels of AOPP before and after 4-week steroid treatment may predict whether patients with SSNS will relapse frequently.

Twenty-eight-year review of childhood renal diseases from renal biopsy data: A single centre in China.

AIM: The aim of the present study was to investigate the clinicopathologic characteristics of biopsy-proven childhood renal diseases and to compare the trends and changes during two different time intervals between 1984 and 2011 at the First Affiliated Hospital of Sun Yat-sen University in China. METHODS: We retrospectively analyzed kidney biopsy data from children with renal diseases and compared the data during two time intervals, namely 1984-1997 and 1998-2011. RESULTS: A total of 1313 children were enrolled in the present study. There were 921 children with primary glomerular disease (PGD) and 312 children with secondary glomerular disease (SGD), accounting for 70.1% and 23.8% of participants, respectively. The major clinical manifestation of PGD was nephrotic syndrome (NS), which accounted for 31.2% of cases, while the main aetiology of SGD was lupus nephritis (40.7%). The main biopsy patterns of PGD were IgA nephritis (27.6%), minimal change disease (24.0%), and mesangial proliferative glomerulonephritis (16.9%). PGD was the major class of disease in both time intervals, but the ratio of PGD decreased over time, while the ratio of SGD and other glomerular diseases increased. PGD was also the major class of disease in each age group; however, the incidence of PGD decreased with increasing age. CONCLUSION: The incidence patterns of paediatric renal diseases changed over the 28-year period of this study. Our results show that different renal diseases characterize different age intervals. Furthermore, there are several associations between clinical presentation and biopsy features in childhood renal disease.

The Smad3/Smad4/CDK9 complex promotes renal fibrosis in mice with unilateral ureteral obstruction.

Transforming growth factor-ß1 (TGF-ß1)/Smad signaling has a central role in the pathogenesis of renal fibrosis. Smad3 and Smad4 are pro-fibrotic, while Smad2 is anti-fibrotic. However, these Smads form heterogeneous complexes, the functions of which are poorly understood. Here we studied Smad complex function in renal fibrosis using the mouse model of unilateral ureteric obstruction. Mice heterozygous for Smad3/4 (Smad3/4+/-) exhibited substantial protection from renal fibrosis through day 7 of obstruction, whereas Smad2/3+/- and Smad2/4+/- mice showed only modest protection. Formation of Smad3/Smad4/CDK9 complexes was an early event following obstruction in wild-type mice, which involved nuclear phosphorylation of the linker regions of Smad3. Significantly, Smad3 or Smad4 deficiency decreased the formation of Smad4/CDK9 or Smad3/CDK9 complex, Smad3 linker phosphorylation, and fibrosis but at different degrees. In vitro, TGF-ß1 stimulation of collagen I promoter activity involved formation of Smad3/Smad4/CDK9 complexes, and overexpression of each component gave additive increases in collagen promoter activity. Co-administration of a CDK9 inhibitor and Smad3-specific inhibition achieved better protection from TGF-ß1-induced fibrotic response in vitro and renal interstitial fibrosis in vivo. Thus formation of Smad3/Smad4/CDK9 complex drives renal fibrosis during ureteral obstruction. Formation of this complex represents a novel target for antifibrotic therapies.