Capturing cerium ions via hydrogel microspheres promotes vascularization for bone regeneration.

The rational design of multifunctional biomaterials with hierarchical porous structure and on-demand biological activity is of great consequence for bone tissue engineering (BTE) in the contemporary world. The advanced combination of trace element cerium ions (Ce3+) with bone repair materials makes the composite material capable of promoting angiogenesis and enhancing osteoblast activity. Herein, a living and phosphorylated injectable porous hydrogel microsphere (P-GelMA-Ce@BMSCs) is constructed by microfluidic technology and coordination reaction with metal ion ligands while loaded with exogenous BMSCs. Exogenous stem cells can adhere to and proliferate on hydrogel microspheres, thus promoting cell-extracellular matrix (ECM) and cell-cell interactions. The active ingredient Ce3+ promotes the proliferation, osteogenic differentiation of rat BMSCs, and angiogenesis of endotheliocytes by promoting mineral deposition, osteogenic gene expression, and VEGF secretion. The enhancement of osteogenesis and improvement of angiogenesis of the P-GelMA-Ce scaffold is mainly associated with the activation of the Wnt/ß-catenin pathway. This study could provide novel and meaningful insights for treating bone defects with biofunctional materials on the basis of metal ions.

Krüppel-like factor 4 modulates the miR-101/COL10A1 axis to inhibit renal fibrosis after AKI by regulating epithelial-mesenchymal transition.

Acute kidney injury (AKI) can progress to renal fibrosis and chronic kidney disease (CKD), which reduces quality of life and increases the economic burden on patients. However, the molecular mechanisms underlying renal fibrosis following AKI remain unclear. This study tested the hypothesis that the Krüppel-like factor 4 (KLF4)/miR-101/Collagen alpha-1X (COL10A1) axis could inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis after AKI in a mouse model of ischemia-reperfusion (I/R)-induced renal fibrosis and HK-2 cells by gene silencing, overexpression, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, dual-luciferase reporter assay, fluorescence in situ hybridization (FISH) and ELISA. Compared with the Sham group, I/R induced renal tubular and glomerular injury and fibrosis, and increased the levels of BUN, serum Scr and neutrophil gelatinase-associated lipocalin (NGAL), Col10a1 and Vimentin expression, but decreased E-cadherin expression in the kidney tissues of mice at 42 days post-I/R. Similarly, hypoxia promoted fibroblastic morphological changes in HK-2 cells and enhanced NGAL, COL10A1, Vimentin, and α-SMA expression, but reduced E-cadherin expression in HK-2 cells. These pathological changes were significantly mitigated in COL10A1-silenced renal tissues and HK-2 cells. KLF4 induces miR-101 transcription. More importantly, hypoxia upregulated Vimentin and COL10A1 expression, but decreased miR-101, KLF4, and E-cadherin expression in HK-2 cells. These hypoxic effects were significantly mitigated or abrogated by KLF4 over-expression in the HK-2 cells. Our data indicate that KLF4 up-regulates miR-101 expression, leading to the downregulation of COL10A1 expression, inhibition of EMT and renal fibrosis during the pathogenic process of I/R-related renal fibrosis.

All-optical interrogation of brain-wide activity in freely swimming larval zebrafish.

We introduce an all-optical technique that enables volumetric imaging of brain-wide calcium activity and targeted optogenetic stimulation of specific brain regions in unrestrained larval zebrafish. The system consists of three main components: a 3D tracking module, a dual-color fluorescence imaging module, and a real-time activity manipulation module. Our approach uses a sensitive genetically encoded calcium indicator in combination with a long Stokes shift red fluorescence protein as a reference channel, allowing the extraction of Ca2+ activity from signals contaminated by motion artifacts. The method also incorporates rapid 3D image reconstruction and registration, facilitating real-time selective optogenetic stimulation of different regions of the brain. By demonstrating that selective light activation of the midbrain regions in larval zebrafish could reliably trigger biased turning behavior and changes of brain-wide neural activity, we present a valuable tool for investigating the causal relationship between distributed neural circuit dynamics and naturalistic behavior.

Activation of mitophagy improves cognitive dysfunction in diabetic mice with recurrent non-severe hypoglycemia.

Recurrent non-severe hypoglycemia (RH) in patients with diabetes might be associated with cognitive impairment. Previously, we found that mitochondrial dysfunction plays an important role in this pathological process; however, the mechanism remains unclear. The objective of this study was to determine the molecular mechanisms of mitochondrial damage associated with RH in diabetes mellitus (DM). We found that RH is associated with reduced hippocampal mitophagy in diabetic mice, mainly manifested by reduced autophagosome formation and impaired recognition of impaired mitochondria, mediated by the PINK1/Parkin pathway. The same impaired mitophagy initiation was observed in an in vitro high-glucose cultured astrocyte model with recurrent low-glucose interventions. Promoting autophagosome formation and activating PINK1/Parkin-mediated mitophagy protected mitochondrial function and cognitive function in mice. The results showed that impaired mitophagy is involved in the occurrence of mitochondrial dysfunction, mediating the neurological impairment associated with recurrent low glucose under high glucose conditions.

COPA syndrome caused by a novel p.Arg227Cys COPA gene variant.

BACKGROUND: COPA syndrome is a recently described and rare monogenic autosomal dominant disease caused by heterozygous missense mutations in the Coatomer Protein Subunit alpha (COPA) gene that encodes the alpha subunit of coat protein complex I (COPI). Its main clinical manifestations are inflammatory lung disease, arthritis, and renal disease. The development of inflammation in COPA syndrome maybe due to abnormal autophagic response and abnormal activation of type I interferon pathway. To date, 59 cases of COPA have been reported worldwide. METHODS: In this case, Trio-whole exome sequencing was employed in the proband and her parents to identify the underlying genetic cause. COPA variant were detected and the clinical presentation of the patient was described. RESULTS: Herein, we report a case of a 5-year-old girl with COPA syndrome who presented with symptoms of arthritis combined with Anti-neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (AAV), and progressive renal decline with minimal pulmonary involvement. Trio-whole exome sequencing was performed which revealed a novel heterozygous likely pathogenic variation in the COPA gene (c.679C>T,p.Arg227Cys), which was maternally inherited. Her mother was a heterozygote, but she had no phenotypic manifestations. No other mutations associated with the clinical phenotype were identified. CONCLUSION: The present identification and characterization of a novel mutation expands the genotypic spectra of the COPA syndrome and provide reference data to guide future clinical diagnosis and treatment of COPA syndrome.

A Self-Adaptive Biomimetic Periosteum Employing Nitric Oxide Release for Augmenting Angiogenesis in Bone Defect Regeneration.

The periosteum plays a vital role in the regeneration of critical-size bone defects and highly comminuted fractures, promoting the differentiation of osteoblasts, accelerating the reconstruction of the vascular network, and guiding bone tissue regeneration. However, the materials loaded with exogenous growth factors are limited by the release and activity of the elements. Therefore, the material structure must be carefully designed for the periosteal function. Here, a self-adaptive biomimetic periosteum strategy is proposed, which is a novel interpenetrating double network hydrogel consisting of diselenide-containing gelatin and calcium alginate (modified natural collagen and polysaccharide) to enhance the stability, anti-swelling, and delayed degradation of the hydrogel. The diselenide bond continuously releases nitric oxide (NO) by metabolizing endogenous nitrosated thiols (RSNO), activates the nitric oxide-cycle guanosine monophosphate (NO-cGMP) signal pathway, coordinates the coupling effect of angiogenesis and osteogenesis, and accelerates the repair of bone defects. This self-adaptive biomimetic periosteum with the interpenetrating double network structure formed by the diselenide-containing gelatin and calcium alginate has been proven to be safe and effective in repairing critical-size bone defects and is expected to provide a promising strategy for solving clinical problems.

Retuning Mitochondrial Apoptosis/Mitophagy Balance via SIRT3-Energized and Microenvironment-Modulated Hydrogel Microspheres to Impede Osteoarthritis.

Full-range therapeutic regimens for osteoarthritis (OA) should consider organs (joints)-tissues (cartilage)-cells (chondrocytes)-organelles cascade, of which the subcellular mitochondria dominate eukaryotic cells' fate, and thus causally influence OA progression. However, the dynamic regulation of mitochondrial rise and demise in impaired chondrocytes and the exact role of mitochondrial metronome sirtuins 3 (SIRT3) is not clarified. Herein, chondrocytes are treated with SIRT3 natural agonist dihydromyricetin (DMY) or chemical antagonist 3-TYP, respectively, to demonstrate the positive action of SIRT3 on preserving cartilage extracellular matrix (ECM). Molecular mechanical investigations disclose that SIRT3-induced chondroprotection depended on the repression of mitochondrial apoptosis (mtApoptosis) and the activation of mitophagy. Inspired by the high-level matrix proteinases and reactive oxygen species (ROS) in the OA environment, by anchoring gelatin methacrylate (GelMA) and benzenediboronic acid (PBA) to hyaluronic acid methacrylate (HAMA) with microfluidic technology, a dual-responsive hydrogel microsphere laden with DMY is tactfully fabricated and named as DMY@HAMA-GelMA-PBA (DMY@HGP). In vivo injection of DMY@HGP ameliorated cartilage abrasion and subchondral bone sclerosis, as well as promoted motor function recovery in post-traumatic OA (PTOA) model via recouping endogenous mtApoptosis and mitophagy balance. Overall, this study unveils a novel mitochondrial dynamic-oriented strategy, holding great promise for the precision treatment of OA.

Mitophagy disorder mediates cardiac deterioration induced by severe hypoglycemia in diabetic mice.

Severe hypoglycemia is closely related to adverse cardiovascular outcomes in patients with diabetes; however, the specific mechanism remains unclear. We previously found that severe hypoglycemia aggravated myocardial injury and cardiac dysfunction in diabetic mice, and that the mechanism of damage was related to mitochondrial oxidative stress and dysfunction. Based on the key regulatory role of mitophagy in mitochondrial quality control, this study aimed to further explore whether the myocardial damage caused by severe hypoglycemia is related to insufficient mitophagy and to clarify their underlying regulatory relationship. After severe hypoglycemia, mitochondrial reactive oxygen species increased, mitochondrial membrane potential and ATP content decreased, and pathological mitochondrial damage was aggravated in the myocardium of diabetic mice. This was accompanied by decreased mitochondrial biosynthesis, increased fusion, and downregulated PTEN-induced kinase 1 (PINK1)/Parkin-dependent mitophagy. Treating diabetic mice with the mitophagy activator and polyphenol metabolite urolithin A activated PINK1/Parkin-dependent mitophagy, reduced myocardial oxidative stress and mitochondrial damage associated with severe hypoglycemia, improved mitochondrial function, alleviated myocardial damage, and ultimately improved cardiac function. Thus, we provide insight into the prevention and treatment of diabetic myocardial injury caused by hypoglycemia to reduce adverse cardiovascular outcomes in patients with diabetes.

Eccentricity-paced geomagnetic field and monsoon rainfall variations over the last 870 kyr.

Whether there are links between geomagnetic field and Earth's orbital parameters remains unclear. Synchronous reconstructions of parallel long-term quantitative geomagnetic field and climate change records are rare. Here, we present 10Be-derived changes of both geomagnetic field and Asian monsoon (AM) rainfall over the last 870 kyr from the Xifeng loess-paleosol sequence on the central Chinese Loess Plateau. The 10BeGM flux (a proxy for geomagnetic field-induced 10Be production rate) reveals 13 consecutive geomagnetic excursions in the Brunhes chron, which are synchronized with the global records, providing key time markers for Chinese loess-paleosol sequences. The 10Be-derived rainfall exhibits distinct ~100 kyr glacial-interglacial cycles, and superimposed precessional (~23 kyr) cycles that match with those in Chinese speleothem δ18O record. We find that changes in the geomagnetic field and AM rainfall share a common ~100 kyr cyclicity, implying a likely eccentricity modulation of both the geomagnetic field and climate.

Study on the correlation between maternal serum uric acid and foetal birth weight in Naqu, Tibet.

In high-altitude regions, low birth weight is mainly caused by hypoxia. We aimed to determine whether maternal serum uric acid (SUC) level was associated with decreased foetal birth weight. The relevant data of individual pregnant women who delivered between 37 and 40 weeks in the People's Hospital of Naqu City, Tibet were retrospectively collected. The correlation between maternal SUC and birth weight was examined using multivariate linear regression analysis and subgroup analysis. The results showed that there was a significant negative correlation between SUC and birth weight in pregnant women with proteinuria, female foetuses, and primiparas. Fitting smoothing curve analysis showed that there was a negative linear correlation between SUC and birth weight in primiparas and female foetuses. Maternal SUC is negatively associated with foetal birth weight in a single pregnancy with proteinuria, primipara, or female foetuses in the Naqu region of Tibet, China.IMPACT STATEMENTWhat is already known on this subject? Preeclampsia associated with hyperuricaemia can affect foetal birth weight, foetal birth weight in plains area is negatively correlated with maternal hyperuricaemia.What do the results of this study add? Maternal SUC was negatively correlated with foetal birth weight, especially in primipara, mothers with proteinuria, and pregnant girls.What are the implications of these findings for clinical practice and/or further research? The results suggest that attention should be paid to SUC in pregnant women, especially in primipara, mothers with proteinuria, and pregnant girls, in the prevention of low birth weight infants in Naqu Plateau area of Tibet.

Growth hormone treatment in pre-pubertal short Chinese children with chronic kidney disease prior to transplantation.

BACKGROUND: The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear. METHODS: This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks. RESULTS: A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P < 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P < 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P < 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P < 0.001], and height [P < 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention. CONCLUSIONS: Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety. IMPACT: The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice.

Mito-TEMPO, a Mitochondria-Targeted Antioxidant, Improves Cognitive Dysfunction due to Hypoglycemia: an Association with Reduced Pericyte Loss and Blood-Brain Barrier Leakage.

Hypoglycemia is associated with cognitive dysfunction, but the exact mechanisms have not been elucidated. Our previous study found that severe hypoglycemia could lead to cognitive dysfunction in a type 1 diabetes (T1D) mouse model. Thus, the aim of this study was to further investigate whether the mechanism of severe hypoglycemia leading to cognitive dysfunction is related to oxidative stress-mediated pericyte loss and blood-brain barrier (BBB) leakage. A streptozotocin T1D model (150 mg/kg, one-time intraperitoneal injection), using male C57BL/6J mice, was used to induce hypoglycemia. Brain tissue was extracted to examine for neuronal damage, permeability of BBB was investigated through Evans blue staining and electron microscopy, reactive oxygen species and adenosine triphosphate in brain tissue were assayed, and the functional changes of pericytes were determined. Cognitive function was tested using Morris water maze. Also, an in vitro glucose deprivation model was constructed. The results showed that BBB leakage after hypoglycemia is associated with excessive activation of oxidative stress and mitochondrial dysfunction due to glucose deprivation/reperfusion. Interventions using the mitochondria-targeted antioxidant Mito-TEMPO in both in vivo and in vitro models reduced mitochondrial oxidative stress, decreased pericyte loss and apoptosis, and attenuated BBB leakage and neuronal damage, ultimately leading to improved cognitive function.

Analysis of anti-M antibody status and blood transfusion strategy in Hunan, China.

Background: By analyzing the detection rate of anti-M antibody in patients with the MNS blood group system in the Hunan area, we aimed to explore its clinical significance and blood transfusion strategy. Methods: We retrospectively analyzed the clinical data of patients who had been confirmed to contain anti-M antibodies through serological methods such as the saline tube method and cassette anti-human globulin method. Results: Irregular antibody screening tests had been applied to 94,452 patients, from which 652 results were positive. Among those positive patients, 93 cases were positive for anti-M antibodies, accounting for 14.26% of the positive rate of irregular antibodies; 11 cases had a blood transfusion history, accounting for 11.8%; 59 cases had a pregnancy history, accounting for 63.4%; and 2 cases had a transplant history, accounting for 2.2%. The patients with anti-M antibodies included 23 pregnant woman, accounting for 24.7%, and 19 tumor patients, accounting for 20.4%. A total of 66 cases were immunoglobulin M (IgM) + immunoglobulin G (IgG) class, accounting for 71.0%, 26 cases were IgM class, accounting for 28.0%, and 1 case was IgG class, accounting for 1.0%. Conclusions: The detection rates of anti-M antibody in the Hunan area and unexpected antibodies in literature reports are mainly related to a pregnancy history, and the type of antibody is predominantly IgM + IgG class. The clinical significance of anti-M antibody cannot be ignored, and three media should be used for cross-matching of blood wherever possible to ensure the safety of blood transfusion.

Low FT3/FT4 Ratio Is Linked to Poor Prognosis of Acute Myocardial Infarction in Euthyroid Patients with Type 2 Diabetes Mellitus.

This is an observational, retrospective, single-center study aimed to determine whether the free triiodothyronine (FT3) to free thyroxine (FT4) ratio was related to acute myocardial infarction (AMI) prognosis in individuals with type 2 diabetes mellitus (T2DM). A total of 294 euthyroid T2DM patients with new-onset AMI were enrolled. FT3/FT4 ratio tertiles were used to categorize patients into Group 1 (FT3/FT4 ≥ 4.3), Group 2 (3.5 ≤ FT3/FT4 < 4.3), and Group 3 (FT3/FT4 < 3.5). Major adverse cardiac events (MACE), including nonfatal myocardial infarction, target vessel revascularization (TVR), and cardiac mortality, served as the primary endpoint. Group 3 demonstrated a considerably higher incidence of MACE than the other two groups over the average follow-up duration of 21 ± 6.5 months (all p < 0.001). Multivariable Cox regression analysis showed that a low FT3/FT4 ratio was an independent risk factor for MACE after AMI (Group 1 as a reference; Group 2: hazard ratio [HR] 1.275, 95% confidence interval [CI]: 0.563−2.889, p = 0.561; Group 3: HR 2.456, 95% CI: 1.105−5.459, p = 0.027). Moreover, the area under the receiver-operating characteristic curve (AUC) indicates a good predictive value of FT3/FT4 ratio for MACE (AUC = 0.70). Therefore, in T2DM patients with AMI, a low FT3/FT4 ratio was strongly linked to poor prognosis.

SIRT3 alleviates mitochondrial dysfunction induced by recurrent low glucose and improves the supportive function of astrocytes to neurons.

Hypoglycemia is an independent risk factor of cognitive impairment in patients with diabetes. Our previous study indicated that dysfunction of astrocytic mitochondria induced by recurrent low glucose (RLG) may account for hypoglycemia-associated neuronal injury and cognitive decline. Sirtuin 3 (SIRT3) is a key deacetylase for mitochondrial proteins and has recently been demonstrated to be an important regulator of mitochondrial function. However, whether mitochondrial dysfunction due to hypoglycemia is associated with astrocytic SIRT3 remains unclear, and few studies have focused on the impact of astrocytic SIRT3 on neuronal survival. In the present work, primary mouse cortical astrocytes cultured in normal glucose (5.5 mM) and high glucose (16.5 mM) were treated with five rounds of RLG (0.1 mM). The results showed that RLG suppressed SIRT3 expression in a glucose-dependent manner. High-glucose culture considerably increased the vulnerability of SIRT3 to RLG, leading to disrupted mitochondrial morphology in astrocytes. Overexpression of SIRT3 markedly improved astrocytic mitochondrial function and reduced RLG-induced oxidative stress. Moreover, SIRT3 suppressed a shift towards a neuroinflammatory A1-like reactive phenotype of astrocytes in response to RLG with reduced IL-1ß, IL-6, and TNFα levels. Furthermore, it elevated brain-derived neurotrophic factor (BDNF) levels and promoted neurite growth by activating BDNF/TrkB signaling in the co-cultured neurons. The present study reveals the probable crosstalk between neurons and astrocytes after hypoglycemic exposure and provides a potential target in treating hypoglycemia-associated neuronal injury.

Extendable Multiple Nodes Recurrent Tracking Framework With RTU+.

Recently, tracking-by-detection has become a popular paradigm in Multiple-object tracking (MOT) for its concise pipeline. Many current works first associate the detections to form track proposals and then score proposalns by manual functions to select the best. However, long-term tracking information is lost in this way due to detection failure or heavy occlusion. In this paper, the Extendable Multiple Nodes Tracking framework (EMNT) is introduced to model the association. Instead of detections, EMNT creates four basic types of nodes including correct, false, dummy and termination to generally model the tracking procedure. Further, we propose a General Recurrent Tracking Unit (RTU++) to score track proposals by capturing long-term information. In addition, we present an efficient generation method of simulated tracking data to overcome the dilemma of limited available data in MOT. The experiments show that our methods achieve state-of-the-art performance on MOT17, MOT20 and HiEve benchmarks. Meanwhile, RTU++ can be flexibly plugged into other trackers such as MHT, and bring significant improvements. The additional experiments on MOTS20 and CTMC-v1 also demonstrate the generalization ability of RTU++ trained by simulated data in various scenarios.

Interleukin-6 Downregulates the Expression of Vascular Endothelial-Cadherin and Increases Permeability in Renal Glomerular Endothelial Cells via the Trans-Signaling Pathway.

The pathogenesis of IgA nephropathy (IgAN) is still unknown, but reportedly, interleukin 6 (IL-6) is involved in this process. However, its role in damaging glomerular endothelial cells is still unclear. Therefore, in this study, to clarify the mechanism of the pathogenesis of IgAN, we investigated the effect of IL-6 on the permeability of glomerular endothelial cells. A rat model of IgAN was established, and the animals divided into two groups, namely, the normal and IgAN groups. Glomerular endothelial cell injury was evaluated via electron microscopy. Furthermore, IL-6-induced changes in the permeability of human renal glomerular endothelial cells (HRGECs) were measured via trans-endothelial resistance (TEER) measurements and fluorescein isothiocyanate-dextran fluorescence. Furthermore, vascular endothelial-cadherin (VE-cadherin) was overexpressed to clarify the effect of IL-6 on HRGEC permeability, and to determine the pathway by which it acts. The classical signaling pathway was blocked by silencing IL-6R and the trans-signaling pathway was blocked by sgp30Fc. In IgAN rats, electron microscopy showed glomerular endothelial cell damage and western blotting revealed a significant increase in IL-6 expression, while VE-cadherin expression decreased significantly in the renal tissues. IL-6/IL-6R stimulation also significantly increased the permeability of HRGECs (p < 0.05). This effect was significantly reduced by VE-cadherin overexpression (p < 0.01). After IL-6R was silenced, IL-6/IL-6R still significantly reduced VE-cadherin expression and sgp30Fc blocked the trans-signaling pathway as well as the upregulation of IL-6/IL-6R-induced VE-cadherin expression. This suggests that IL-6 mainly acts via the trans-signaling pathway. IL-6 increased the permeability of HRGECs by decreasing the expression of VE-cadherin via the trans-signaling pathway.

Establishment of prognostic nomogram for high-grade parotid gland mucoepidermoid carcinoma based on the SEER database.

Purpose: We aim to investigate the clinical factors that affect the prognosis of overall survival (OS) for patients with high-grade parotid gland mucoepidermoid carcinoma (high-grade pMEC) and construct a nomogram for prognosis prediction. Subjects and method: Totally, 519 patients diagnosed as high-grade pMEC from the surveillance, epidemiology, and end results (SEER) database between 2004 and 2015 were reviewed. Independent prognostic factors for OS were identified by univariate and multivariate Cox regression analyses. Nomogram was generated to predict the individual's 3- and 5- year OS rates by using R software. Prediction ability was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) and model calibration was evaluated through calibration plots. Decision curve analysis (DCA) was used to assess the clinical usefulness and net benefit. Results: The results of univariate analysis demonstrated that age, AJCC stage, T stage, N stage, M stage, extraparenchymal lesions, regional lymph nodes status, lymph node dissection status, radiotherapy, chemotherapy, and surgery were significantly correlated with the OS (P < 0.05). Multivariate Cox regression analyses showed that older age at diagnosis, advanced AJCC stage, and positive regional lymph nodes were independent risk factors for OS. In addition, the present study revealed that radiotherapy and surgery were independent protective factors for OS (P < 0.05). The nomograms showed accurate prognostic ability that individually predict 3-years and 5-years overall survival (OS) rates based on age, AJCC stage, regional lymph nodes status, radiotherapy, and surgery. The area under the receiver operating characteristic (ROC) curve (AUC) of the nomogram used to predict the 3-year and 5-year overall survival rate were 0.779 and 0.793, indicating that the model had a good predictive power for the overall survival in high-grade pMEC patient. Conclusions: Using the SEER database, we performed univariate and multivariate analyses to determine independent prognostic factors in high-grade pMEC patients. Subsequently, we constructed and validated a prognostic nomogram to predict 3-and 5-year OS rates based on the SEER database and can assist clinicians to intuitively evaluate prognosis of high-grade pMEC patients.

The association between skinfold thicknesses and estimated glomerular filtration rate in adolescents: a cross-sectional study.

BACKGROUND: Obesity is one of the causes of glomerular hyperfiltration. Studies on the relationship between body fat content and glomerular hyperfiltration have been limited to special children. Therefore, we aimed to evaluate the correlation between skinfold thickness, which represents body fat content, and estimated glomerular filtration rate (eGFR). METHODS: The cross-sectional study included 6655 participants (3532 boys and 3123 girls; age: 12 - 17.99 years); data was obtained from the National Health and Nutrition Examination Survey (NHANES; 2001-2010). The independent variables were subscapular skinfold thickness and triceps skinfold thickness. The dependent variable was eGFR. We used multivariate linear regression models to evaluate their associations and also performed subgroup analyses. RESULTS: After adjusting for age, standing height, race, family income, blood urea nitrogen and uric acid variables, multivariate regression analysis identified that triceps skinfold thickness and subscapular skinfold thickness were positively correlated with eGFR and glomerular hyperfiltration in boys. In subgroup analyses stratified by age and body mass index, triceps skinfold thickness was also associated with glomerular hyperfiltration in boys. There was a linear relationship between triceps skinfold thickness and eGFR in boys (ß = 0.389, P < 0.001) and girls (ß = 0.159, P = 0.0003). CONCLUSIONS: Triceps skinfold thickness and subscapular skinfold thickness are positively correlated with eGFR and glomerular hyperfiltration in US male adolescents. In all adolescents, there is a linear relationship between triceps skinfold thickness and eGFR.