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Bismuth halide hybrid perovskites have emerged as promising alternatives to their lead halide homologs because of high chemical stability, low toxicity, and structural diversity. However, their advancements in optoelectronic field are plagued with poor charge transport, due to considerable microstrain triggered by bulky spacer. Herein, the di-tertiary ammonium spacer (N,N,N',N'-tetramethyl-1,4-butanediammonium, TMBD) is explored to direct stable 1D bismuth bromide lattice structure with relaxed microstrain. Compared to the primary pentamethylenediamine (PD)2+, the (TMBD)2+ adopting alternating alignment enables a unique H-bonds mode to distort the configuration of inorganic layers to form corner-sharing [BiBr5] near-regular chains with narrower bandgap, lower exciton binding energy, and reduced carrier-lattice interactions, thereby facilitating charge-carrier transport. Moreover, the (TMBD)2+ spacers largely suppress ion migration in perovskite lattice, as substantiated by the experimental and theoretical investigations. Consequently, (TMBD)BiBr5 single crystal photodetector delivers a 185-fold increase in current on/off ratio with respect to (PD)BiBr5 under white light irradiation, considerable responsivity (≈82.97 mA W-1), detectivity (≈8.06 ×1011 Jones) under weak light (0.02 mW cm-2) irradiation, in the top rank of the reported hybrid bismuth halide perovskites. This finding offers novel design criterion for high-performance lead-free perovskites.
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PURPOSE: This study aims to develop and validate a prediction model for delirium in elderly ICU patients and help clinicians identify high-risk patients at the early stage. METHODS: Patients admitted to ICU for at least 24 h and using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database (76,943 ICU stays from 2008 to 2019) were considered. Patients with a positive delirium test in the first 24 h and under 65 years of age were excluded. Two prediction models, machine learning extreme gradient boosting (XGBoost) and logistic regression (LR) model, were developed and validated to predict the onset of delirium. RESULTS: Of the 18,760 patients included in the analysis, 3463(18.5%) were delirium positive. A total of 22 significant predictors were selected by LASSO regression. The XGBoost model demonstrated superior performance over the LR model, with the Area Under the Receiver Operating Characteristic (AUC) values of 0.853 (95% confidence interval [CI] 0.846-0.861) and 0.831 (95% CI 0.815-0.847) in the training and testing datasets, respectively. Moreover, the XGBoost model outperformed the LR model in both calibration and clinical utility. The top five predictors associated with the onset of delirium were sequential organ failure assessment (SOFA), infection, minimum platelets, maximum systolic blood pressure (SBP), and maximum temperature. CONCLUSION: The XGBoost model demonstrated good predictive performance for delirium among elderly ICU patients, thus assisting clinicians in identifying high-risk patients at the early stage and implementing targeted interventions to improve outcome.
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BACKGROUND AND AIMS: The role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. METHODS AND RESULTS: Leveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3-5. The study finally included 2644 patients with CKD stages 3-5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. CONCLUSIONS: Both higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3-5.
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Biomarcadores , Enfermedades Cardiovasculares , Causas de Muerte , Hiperuricemia , Encuestas Nutricionales , Insuficiencia Renal Crónica , Ácido Úrico , Humanos , Ácido Úrico/sangre , Masculino , Femenino , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Persona de Mediana Edad , Medición de Riesgo , Biomarcadores/sangre , Anciano , Hiperuricemia/sangre , Hiperuricemia/mortalidad , Hiperuricemia/diagnóstico , Factores de Tiempo , Pronóstico , Estados Unidos/epidemiología , Factores de Riesgo , Adulto , Factores de Riesgo de Enfermedad CardiacaRESUMEN
BACKGROUND: This network meta-analysis (NMA) aimed to compare the clinical advantage of four commonly used peritoneal dialysis catheters (PDCs) including the Swan neck segment with straight tip (Swan neck + S), Tenckhoff segment with straight tip (Tenckhoff + S), Swan neck segment with coiled tip (Swan neck + C) and Tenckhoff segment with coiled tip (Tenckhoff + C). METHODS: Randomised clinical trials were searched from PubMed, Embase, the Cochrane Register of clinical trials, China National Knowledge Infrastructure (CNKI) and ChinaInfo from their inception until July 31, 2022. Meta-analysis was performed using Stata 14.0 and RevMan 5.3.5 software to evaluate the four commonly used PDCs. RESULTS: Seventeen studies involved 1578 participants were included. NMA showed that compared with Swan neck + C, Swan neck + S significantly reduced catheter tip migration (OR 0.47 95% CI 0.22-0.99). Tenckhoff + S was more effective in reducing catheter dysfunction (OR 0.42, 95% CI 0.23-0.79), catheter tip migration with dysfunction (OR 0.19, 95% CI 0.05-0.78) and catheter removal (OR 0.56, 95% CI 0.34-0.93) which were consistent with the pairwise meta-analysis. According to the surface under the cumulative ranking curve, Swan neck + S emerged as the best PDC in the reduction of catheter tip migration (83.3%), followed by Tenckhoff + S (79.4%). Moreover, Tenckhoff + S (86.5%, 76.3%) and Swan neck + S (72.3, 86.9%) ranked as the first and second PDC for 1 and 2-year technique survival which was significantly higher than those of the other two PDCs. CONCLUSION: Our NMA showed Swan neck + S and Tenckhoff + S tended to be more efficacious than Swan neck + C and Tenckhoff + C in lowering the mechanical dysfunction and prolonging the technique survival, which may contribute to better clinical decisions. More randomised controlled trials with larger scales and higher quality are needed in order to obtain more credible evidence.
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The family of polar hybrid perovskites, in which bulk photovoltaic effects (BPVEs) drive steady photocurrent without bias voltage, have shown promising potentials in self-powered polarization-sensitive photodetection. However, reports of BPVEs in 3D perovskites remain scare, being mainly hindered by the limited dipole moment or lack of symmetry breaking. Herein, a polar 3D perovskitoid, (BDA)Pb2Br6 (BDA = NH3C4H8NH3), where the spontaneous polarization (Ps)-induced BPVE drives self-powered photodetection of polarized-light is reported. Emphatically, the edge-sharing Pb2Br10 dimer building unit allows the optical anisotropy and polarity in 3D (BDA)Pb2Br6, which triggers distinct optical absorption dichroism ratio of ≈2.80 and BPVE dictated photocurrent of 3.5 µA cm-2. Strikingly, these merits contribute to a polarization-sensitive photodetection with a high polarization ratio (≈4) under self-powered mode, beyond those of 2D hybrid perovskites and inorganic materials. This study highlights the potential of polar 3D perovskitoids toward intelligent optoelectronic applications.
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Background: The incidence of concurrent immunoglobulin A nephropathy and membranous nephropathy (cIgAN/MN) is low and rarely reported, and the prognosis of patients with cIgAN/MN remains unclear. This study was designed to compare the clinical and prognostic characteristics of cIgAN/MN with IgAN and MN and to identify crucial factors influencing the outcomes of patients with cIgAN/MN. Methods: We included biopsy-proven cIgAN/MN patients between December 2012 and December 2020 at Xijing Hospital. In the same period, propensity score matching was employed to select an equal number of IgAN and MN patients according to the following criteria: age, sex, and follow-up time. The primary endpoint was defined as a composite of eGFR decline ≥30 %, end-stage renal disease, or death. The patient survival rate was examined using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis models were utilized to identify the risk factors affecting renal prognosis. Results: A total of 135 patients were finally included in this study and 35 (25.9 %) reached the primary endpoint. The median follow-up time of cIgAN/MN was 45.9 (24.0, 72.0) months. Compared to the IgAN group, the cIgAN/MN group exhibited a lower cumulative incidence rate of composite renal endpoints (P = 0.044), while no significant difference was found between MN and cIgAN/MN patients (P = 0.211). Univariate Cox analysis revealed that mean arterial pressure, serum potassium, blood urea nitrogen, serum IgA, segmental glomerulosclerosis (S1), and MN staging were associated with an increased risk of renal composite endpoints. The multivariate Cox regression analysis of clinical variables plus histological lesion scoring demonstrated that potassium (HR = 14.350, 95 % CI 2.637-78.090, P = 0.002), serum IgA (HR = 1.870, 95 % CI 1.109-3.153, P = 0.019), and S1 (HR = 11.965, 95 % CI 2.166-66.105, P = 0.004) were independent risk factors influencing renal outcomes in cIgAN/MN patients. Conclusion: The prognosis of cIgAN/MN patients may exhibit an intermediate pattern between IgAN and MN, leaning towards being more similar to MN in certain aspects. Within the cIgAN/MN cohort, potassium, and serum IgA may be more predictive of rapid progression of renal endpoints, and S1 may indicate a more aggressive disease course.
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The detection of intrinsic protein fluorescence is a powerful tool for studying proteins in their native state. Thanks to its label-free and stain-free feature, intrinsic fluorescence detection has been introduced to polyacrylamide gel electrophoresis (PAGE), a fundamental and ubiquitous protein analysis technique, to avoid the tedious detection process. However, the reported methods of intrinsic fluorescence detection were incompatible with online PAGE detection or standard slab gel. Here, we fulfilled online intrinsic fluorescence imaging (IFI) of the standard slab gel to develop a PAGE-IFI method for real-time and quantitative protein detection. To do so, we comprehensively investigated the arrangement of the deep-UV light source to obtain a large imaging area compatible with the standard slab gel, and then designed a semi-open gel electrophoresis apparatus (GEA) to scaffold the gel for the online UV irradiation and IFI with low background noise. Thus, we achieved real-time monitoring of the protein migration, which enabled us to determine the optimal endpoint of PAGE run to improve the sensitivity of IFI. Moreover, online IFI circumvented the broadening of protein bands to enhance the separation resolution. Because of the low background noise and the optimized endpoint, we showcased the quantitative detection of bovine serum albumin (BSA) with a limit of detection (LOD) of 20 ng. The standard slab gel provided a high sample loading volume that allowed us to attain a wide linear range of 0.03-10 µg. These results indicate that the PAGE-IFI method can be a promising alternative to conventional PAGE and can be widely used in molecular biology labs.
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Imagen Óptica , Albúmina Sérica Bovina , Electroforesis en Gel de PoliacrilamidaRESUMEN
Halide composition engineering has been demonstrated as an effective strategy for optical and electronic properties modulation in 3D perovskites. While the impact of halide mixing on the structural and charge transport properties of 3D perovskitoids remains largely unexplored. Herein, it is demonstrated that bromine (Br) mixing in 3D (NMPDA)Pb2 I6 (NMPDA = N-methyl-1,3-propane diammonium) perovskitoid yields stabilized (NMPDA)Pb2 I4 Br2 with specific ordered halide sites, where Br ions locate at the edge-sharing sites. The halide ordered structure enables stronger H-bonds, shorter interlayer distance, and lower octahedra distortion in (NMPDA)Pb2 I4 Br2 with respect to the pristine (NMPDA)Pb2 I6 . These attributes further result in high ion migration activation energy, low defect states density, and enhanced carrier mobility-lifetime product (µτ), as underpinned by the electrical properties investigation and DFT calculations. Remarkably, the parallel configured photodetector based on (NMPDA)Pb2 I4 Br2 single crystal delivers a high on/off current ratio of 3.92 × 103 , a satisfying photoresponsivity and detectivity of 0.28 A W-1 and 3.05 × 1012 Jones under 10.94 µW cm-2 irradiation, superior to that of (NMPDA)Pb2 I6 and the reported 3D perovskitoids. This work sheds novel insight on exploring 3D mixed halide perovskitoids toward advanced and stable optoelectronic devices.
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Polyacrylamide gel electrophoresis (PAGE) is one of the most popular techniques for the separation and detection of nucleic acids. However, it requires a complicated detection procedure and offline detection format, which inevitably leads to band broadening and thus compromises the separation resolution. To overcome this problem, we developed an online PAGE (OPAGE) platform by integrating the gel electrophoresis apparatus with the gel imaging system, so as to obviate the need for the complicated detection procedure. Notably, OPAGE enabled the real-time monitoring of the separation process and the immediate imaging of the separation results once the electrophoresis ended. Using a series of synthetic DNAs with different lengths as samples, we demonstrated that the OPAGE platform enhanced 32-64 % of the number of theoretical plates, showed a robust dynamic range of 0.1-12.5 ng/µL, and realized a limit of detection as low as 0.08 ng/µL DNA. Based on our results, we anticipate that the OPAGE platform is a promising alternative to traditional nucleic acid gel electrophoresis for simple and high-resolution detection and quantification and nucleic acid.
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ADN , Ácidos Nucleicos , Electroforesis en Gel de PoliacrilamidaRESUMEN
BACKGROUND: Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of the gut microbiota in individuals with LN have not been fully clarified. METHODS: The PubMed, Web of Science, and Embase databases were systematically searched for clinical and animal studies related to the relationship between LN and gut microbiota from inception until October 1, 2023. A semiquantitative analysis was used to assess the changes in gut microbial profiles. RESULTS: A total of 15 clinical studies were selected for analysis, which included 138 LN patients, 441 systemic lupus erythematosus patients, and 1526 healthy controls (HCs). Five different types of LN mouse models were included in 5 animal studies. The alpha diversity was decreased in LN patients compared to HCs. A significant decrease in the Firmicutes/Bacteroidetes (F/B) ratio is considered a hallmark of pathological conditions. Specifically, alterations in the abundance of the phylum Proteobacteria, genera Streptococcus and Lactobacillus, and species Ruminococcus gnavus and Lactobacillus reuteri may play a critical role in the pathogenesis of LN. Remarkably, the gut taxonomic chain Bacteroidetes-Bacteroides-Bacteroides thetaiotaomicron was enriched in LN patients, which could be a crucial characteristic of LN patients. The increased level of interleukin-6, imbalance of regulatory T cells and T helper 17 cells, and decreased level of the intestinal tight junction proteins zonula occludens-1 and claudin-1 also might be related to the pathogenesis of LN. CONCLUSIONS: Specific changes in the abundance of gut microbiota such as decreased F/B ratio, and the level of inflammatory indicators, and markers of intestinal barrier dysfunction may play a crucial role in the pathogenesis of LN. These factors could be effective diagnostic and potential therapeutic targets for LN.
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Microbioma Gastrointestinal , Enfermedades Intestinales , Lupus Eritematoso Sistémico , Nefritis Lúpica , Animales , Ratones , Humanos , Interleucina-6RESUMEN
Broadband emissions from low-dimensional hybrid perovskites have aroused intense interest. However, the achievement of broadband red emission in lead halide perovskites remains challenging. Herein, we report a one-dimensional (1D) hybrid lead bromide perovskitoid, (HM)Pb2Br6 (HM = hexamethonium), featuring a corrugated "3 × 3" [Pb2Br6]2- chain. The unique structure results in intriguingly red emission peaking at 692 nm, with a PLQY of around 6.24%. Our spectroscopic and computational studies reveal that the red emission derives from self-localized Pb23+, Pb3+ and Br2- species confined within the inorganic lead bromide lattice that function as radiative centres. This finding will benefit the design of perovskite systems for efficient red emission.
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Acute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifest that Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increase in AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this study aims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.
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Lesión Renal Aguda , Insuficiencia Renal Crónica , Humanos , Triptófano/metabolismo , Insuficiencia Renal Crónica/etiología , Quinurenina , Transducción de Señal , Lesión Renal Aguda/etiologíaRESUMEN
Decades of knockout analyses have highlighted the crucial involvement of estrogen receptors and downstream genes in controlling mating behaviors. More recently, advancements in neural circuit research have unveiled a distributed subcortical network comprising estrogen-receptor or estrogen-synthesis-enzyme-expressing cells that transforms sensory inputs into sex-specific mating actions. This review provides an overview of the latest discoveries on estrogen-responsive neurons in various brain regions and the associated neural circuits that govern different aspects of male and female mating actions in mice. By contextualizing these findings within previous knockout studies of estrogen receptors, we emphasize the emerging field of "circuit genetics", where identifying mating behavior-related neural circuits may allow for a more precise evaluation of gene functions within these circuits. Such investigations will enable a deeper understanding of how hormone fluctuation, acting through estrogen receptors and downstream genes, influences the connectivity and activity of neural circuits, ultimately impacting the manifestation of innate mating actions.
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Estrógenos , Receptores de Estrógenos , Animales , Masculino , Femenino , Ratones , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Neuronas/fisiología , Encéfalo/fisiologíaRESUMEN
BACKGROUND: Delirium is a common complication clinically and is associated with the poor outcomes, yet it is frequently unrecognised and readily disregarded. Although the 3-minute diagnostic interview for confusion assessment method-defined delirium (3D-CAM) has been used in a variety of care settings, a comprehensive evaluation of its accuracy in all available care settings has not been performed. OBJECTIVE: This study aimed to evaluate the diagnostic test accuracy of the 3D-CAM in delirium detection through a systematic review and meta-analysis. METHODS: We systematically searched PubMed, EMBASE, the Cochrane Library, Web of Science, CINAHL (EBSCO) and ClinicalTrials.gov published from inception to 10 July 2022. The quality assessment of the diagnostic accuracy studies-2 tool was applied to evaluate methodological quality. A bivariate random effects model was used to pool sensitivity and specificity. RESULTS: Seven studies with 1,350 participants and 2,499 assessments were included, which were carried out in general medical wards, intensive care units, internal medical wards, surgical wards, recovery rooms and post-anaesthesia care units. The prevalence of delirium ranged from 9.1% to 25%. The pooled sensitivity and specificity were 0.92 (95% confidence interval [CI] 0.87-0.95) and 0.95 (95% CI 0.92-0.97), respectively. The pooled positive likelihood ratio was 18.6 (95% CI 12.2-28.2), the negative likelihood ratio was 0.09 (95% CI 0.06-0.14) and the diagnostic odds ratio was 211 (95% CI 128-349). Moreover, the area under the curve was 0.97 (95% CI 0.95-0.98). CONCLUSIONS: The 3D-CAM has good diagnostic accuracy for delirium detection in different care settings. Further analyses illustrated that it had comparable diagnostic accuracy in older adults and patients with dementia or known baseline cognitive impairment. In conclusion, the 3D-CAM is recommended for clinical delirium detection.
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Delirio , Humanos , Anciano , Delirio/diagnóstico , Sensibilidad y Especificidad , Unidades de Cuidados Intensivos , Hospitales , Habitaciones de PacientesRESUMEN
Intrinsic fluorescence imaging (IFI) has been used for the stain-free detection of proteins in slab gel. However, complicated detection setups and small irradiation area limited the development of facile, online, and portable imaging of the whole slab gel. We here designed a quadruple UV LED array to produce even and powerful area light for direct irradiation of gel electrophoresis chip (GEC) at 275 nm. In addition, we only used a filter of 365 nm, a UV camera lens, and a CCD for IFI detection. We integrated the simple detection setup with the small GEC to construct the IFI-GEC device with a portable size of 15 × 15 × 38 cm. We detected three model proteins to demonstrate the good evenness of the LED array and the online imaging of the whole GEC. Furthermore, the reproducible IFI-GEC detection was completed within 10 min and the LOD was as low as 40 ng for lysozyme detection. All results indicated the potential of the IFI-GEC device for online and portable detection of proteins without staining.
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Electroforesis , Proteínas , Imagen Óptica/métodos , Proteínas/análisis , Coloración y EtiquetadoRESUMEN
BACKGROUND: The spectrum of biopsy-confirmed kidney disease varies with regions and periods. We describe the distribution of pathological types and epidemiological characteristics of kidney diseases in Northwest China due to regional differences in geographical environment, social economy, and dietary habits. METHODS: Kidney biopsy cases from 2005 to 2020 in Xijing Hospital were retrospectively analyzed. Pathological characteristics of patients in different periods were analyzed using the t test or chi-square test. Joinpoint regression was used to analyze trends in pathological types and disease spectrum. RESULTS: A total of 10,528 eligible patients were included. Primary glomerular disease (PGD) accounted for the majority of the cases and exhibited an obvious downward trend, whereas secondary glomerular disease (SGD) showed an obvious upward trend. Among PGD, immunoglobulin A nephropathy (IgAN) remained the most common pathological type, and the detection rate of membranous nephropathy (MN) was significantly increased. Among SGD, Henoch-Schönlein purpura nephritis (HSPN) was the most common pathological type and may present a significant characteristic of Northwest China. Diabetic nephropathy (DN) exhibited the most obvious upward trend in the whole process, whereas the fastest growth since 2012 was in hypertensive nephropathy. CONCLUSION: The proportion of SGD increased whereas PGD declined. IgAN remained the most common PGD, and HSPN was the most common SGD. MN and DN showed the most obvious upward trend among PGD and SGD, respectively. Changes in the spectrum of kidney disease, especially the constituent ratio of SGD, pose a great challenge to public health.
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Objective: To investigate the effect of uric acid on the clinicopathological characteristics and prognosis of immunoglobulin A nephropathy (IgAN) in patients with stage 3-4 chronic kidney disease (CKD). Methods: The clinical and pathological data of 263 IgAN patients who had stage 3-4 CKD and who had confrimed diagosis through renal biopsy at the First Affiliated Hospital of Air Force Medical University between December 2008 and January 2020 were retrospectively collected. According to the levels of uric acid, the patients were divided into a hyperuricemia group (n=102) and a normal uric acid group (n=161), and the clinicopathological characteristics of the two groups were compared accordingly. With progression to end-stage renal disease or death as the endpoint event, the renal survival rate of the two groups was compared by the Kaplan-Meier method and the relationship between uric acid and the prognosis was analyzed by Cox regression and LASSO regression. Results: Compared with the normal uric acid group, the hyperuricemia group had a significantly higher proportion of male patients and patients with a history of hypertension, a significantly higher level of blood urea nitrogen, and lower levels of estimated glomerular filtration rate and high-density lipoprotein. In terms of pathology, patients in the hyperuricemia group had significantly higher proportion of glomerulosclerosis, higher mesangial hypercellularity, and higher tubular atrophy/interstitial fibrosis (P<0.05). Kaplan-Meier curve showed that there was a significant difference in renal survival rate between the two groups (P<0.0001). LASSO regression showed that high uric acid was a risk factor for the prognosis of IgAN patients with stage 3-4 CKD. Further multivariate Cox analysis showed that, compared with the normal uric acid group, the hyperuricemia group had a higher risk of incurring composite outcomes (hazard ratio [HR]=1.61, 95% confidence interval [CI]: 1.10-2.34). When uric acid was used as a continuous variable, the increase of 1 mg/dL in uric acid concentration was associated with an increased HR of 1.18 (95% CI: 1.08-1.29) for the composite outcome. Conclusion: High uric acid is a risk factor for poor renal prognosis in IgAN patients with stage 3-4 CKD and reducing uric acid levels may effectively improve the prognosis of high-risk IgAN patients.
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Glomerulonefritis por IGA , Hiperuricemia , Insuficiencia Renal Crónica , Humanos , Masculino , Glomerulonefritis por IGA/complicaciones , Estudios Retrospectivos , Ácido Úrico , Hiperuricemia/complicaciones , Hiperuricemia/patología , Progresión de la Enfermedad , Pronóstico , Insuficiencia Renal Crónica/complicaciones , Tasa de Filtración GlomerularRESUMEN
Behavioral observations suggest a connection between anxiety and predator defense, but the underlying neural mechanisms remain unclear. Here we examine the role of the anterior hypothalamic nucleus (AHN), a node in the predator defense network, in anxiety-like behaviors. By in vivo recordings in male mice, we find that activity of AHN GABAergic (AHNVgat+) neurons shows individually stable increases when animals approach unfamiliar objects in an open field (OF) or when they explore the open-arm of an elevated plus-maze (EPM). Moreover, object-evoked AHN activity overlap with predator cue responses and correlate with the object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHNVgat+ neurons reduces object and open-arm avoidance. Furthermore, retrograde viral tracing identifies the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHNVgat+ neurons in driving avoidance behaviors in anxiogenic situations. Thus, convergent activation of AHNVgat+ neurons serves as a shared mechanism between anxiety and predator defense to promote behavioral avoidance.
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Núcleo Hipotalámico Anterior , Neuronas GABAérgicas , Masculino , Animales , Ratones , Trastornos de Ansiedad , Ansiedad , HipocampoRESUMEN
Background: Emerging evidence revealed that gut microbial dysbiosis is implicated in the development of plasma cell dyscrasias and amyloid deposition diseases, but no data are available on the relationship between gut microbiota and immunoglobulin light chain (AL) amyloidosis. Methods: To characterize the gut microbiota in patients with AL amyloidosis, we collected fecal samples from patients with AL amyloidosis (n=27) and age-, gender-, and BMI-matched healthy controls (n=27), and conducted 16S rRNA MiSeq sequencing and amplicon sequence variants (ASV)-based analysis. Results: There were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of Actinobacteriota and Verrucomicrobiota was significantly higher, while Bacteroidota reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including Bifidobacterium, Akkermansia, and Streptococcus were enriched, while only 4 genera including Faecalibacterium, Tyzzerella, Pseudomonas, and Anaerostignum decreased evidently in patients with AL amyloidosis. Notably, 5 optimal ASV-based microbial markers were identified as the diagnostic model of AL amyloidosis and the AUC value of the train set and the test set was 0.8549 (95% CI 0.7310-0.9789) and 0.8025 (95% CI 0.5771-1), respectively. With a median follow-up of 19.0 months, further subgroup analysis also demonstrated some key gut microbial markers were related to disease severity, treatment response, and even prognosis of patients with AL amyloidosis. Conclusions: For the first time, we demonstrated the alterations of gut microbiota in AL amyloidosis and successfully established and validated the microbial-based diagnostic model, which boosted more studies about microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis in the future.
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Microbioma Gastrointestinal , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Humanos , Microbioma Gastrointestinal/fisiología , ARN Ribosómico 16S/genética , Disbiosis/microbiología , Heces/microbiología , BiomarcadoresRESUMEN
Multiple myeloma (MM), an incurable hematological malignancy with clonal proliferation of plasma cells, is mainly characterized by excessive production of monoclonal immunoglobulins and free light chains (FLCs). Kidney injury is one of the main clinical manifestations and is also a significant predictor of the prognosis of symptomatic MM patients, especially those who require dialysis-supported treatment. Overproduction of FLCs is the trigger for kidney injury, as they can induce the transcription of inflammatory and profibrotic cytokines in the proximal tubule and bind to Tamm-Horsfall protein in the distal tubules to form casts that obstruct the tubules, leading to kidney injury and even renal fibrosis. In addition to traditional antimyeloma treatment, high-cutoff hemodialysis (HCO-HD), which can effectively remove FLCs in vitro, has attracted much attention in recent years. Due to its greater membrane pore size, it has significant advantages in removing larger molecules and can be applied in rhabdomyolysis, sepsis, and even myeloma cast nephropathy. However, mounting questions have recently been raised regarding whether HCO-HD can truly provide clinical benefits in MM patients with acute kidney injury (AKI). Therefore, in this study, we discussed the pathological causes of AKI secondary to MM and summarized the current situation of HCO-HD in MM patients compared with other available extracorporeal techniques. In addition, pivotal clinical trials that reflect the ability of the clearance of FLCs and the side effects of HCO-HD are highlighted, and the relevant protocol of HCO-HD is also provided to assist clinicians in decision-making.