ABSTRACT
Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.
Subject(s)
COVID-19 , Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Mice , SARS-CoV-2/geneticsABSTRACT
Neurovascular coupling serves as an essential neurophysiological mechanism in functional neuroimaging, which is generally presumed to be robust and invariant across different physiological states, encompassing both task engagement and resting state. Nevertheless, emerging evidence suggests that neurovascular coupling may exhibit state dependency, even in normal human participants. To investigate this premise, we analyzed the cross-frequency spectral correspondence between concurrently recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data, utilizing them as proxies for neurovascular coupling during the two conditions: an eye-open-eye-close (EOEC) task and a resting state. We hypothesized that given the state dependency of neurovascular coupling, EEG-fMRI spectral correspondences would change between the two conditions in the visual system. During the EOEC task, we observed a negative phase-amplitude-coupling (PAC) between EEG alpha-band and fMRI visual activity. Conversely, in the resting state, a pronounced amplitude-amplitude-coupling (AAC) emerged between EEG and fMRI signals, as evidenced by the spectral correspondence between the EEG gamma-band of the midline occipital channel (Oz) and the high-frequency fMRI signals (0.15-0.25 Hz) in the visual network. This study reveals distinct scenarios of EEG-fMRI spectral correspondence in healthy participants, corroborating the state-dependent nature of neurovascular coupling.
Subject(s)
Magnetic Resonance Imaging , Neurovascular Coupling , Humans , Magnetic Resonance Imaging/methods , Neurovascular Coupling/physiology , Brain Mapping/methods , Electroencephalography/methods , Eye , Brain/diagnostic imaging , Brain/physiologyABSTRACT
Nonvolatile electrical control of two-dimensional (2D) van der Waals (vdW) magnetism is important for spintronic devices. Here, using first-principles calculations, we systematically investigated the magnetic properties of the MXene Hf2MnC2O2 combined with the ferroelectric MXene Sc2CO2. When flipping the electric polarization of Sc2CO2, a transition between a semiconductor and a half-metal occurs in the Hf2MnC2O2 monolayer. Moreover, the ferromagnetic exchange parameter J1 can be enhanced to 9.67 meV under polarized P↑ of Sc2CO2, much larger than those of the pristine Hf2MnC2O2 monolayer and Hf2MnC2O2/Sc2CO2-P↓. In addition, the easy magnetization axis of the Hf2MnC2O2 monolayer is also dependent on the polarization orientation of Sc2CO2. Our results indicate a multiferroic heterostructure based on MXenes, offering an effective way for obtaining nonvolatile electrical control of electronic and magnetic properties.
ABSTRACT
OBJECTIVE: The clinical manifestations of methamphetamine (METH)-associated psychosis (MAP) and acute paranoid schizophrenia (SCZ) are similar. This study aims to assess regional cerebral blood flow (rCBF) in individuals who use METH and in those with SCZ using the MRI arterial spin labeling (ASL) technique. METHODS: We prospectively recruited 68 participants and divided them into four groups: MAP (N = 15), SCZ (N = 13), METH users with no psychosis (MNP; N = 22), and normal healthy controls (CRL; N = 18). We measured rCBF using an MRI three-dimensional pseudo-continuous ASL sequence. Clinical variables were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS). Group-level rCBF differences were analyzed using a two-sample t-test. RESULTS: Decreased rCBF was found in the precuneus, premotor cortex, caudate nucleus, dorsolateral prefrontal cortex, and thalamus in the MNP group compared with the CRL group. The MAP group had significantly decreased rCBF in the precuneus, hippocampus, anterior insula, inferior temporal gyrus, inferior orbitofrontal gyrus, and superior occipital gyrus compared with the MNP group. Increased rCBF in the precuneus and premotor cortex was seen in the MAP group compared with the SCZ group. rCBF in the precuneus and premotor cortex significantly correlated negatively with the PANSS but correlated positively with BACS scores in the MAP and SCZ groups. CONCLUSION: METH exposure was associated with decreased rCBF in the precuneus and premotor cortex. Patients with MAP exhibited higher rCBF than those with SCZ, implying preserved insight and favorable outcomes. rCBF can therefore potentially serve as a diagnostic approach to differentiate patients with MAP from those with SCZ.
ABSTRACT
Practicing mindfulness, focusing attention on the internal and external experiences occurring in the present moment with open and nonjudgement stance, can lead to the development of emotional regulation skills. Yet, the effective connectivity of brain regions during mindfulness has been largely unexplored. Studies have shown that mindfulness practice promotes functional connectivity in practitioners, potentially due to improved emotional regulation abilities and increased connectivity in the lateral prefrontal areas. To examine the changes in effective connectivity due to mindfulness training, we analyzed electroencephalogram (EEG) signals taken before and after mindfulness training, focusing on training-related effective connectivity changes in the frontal area. The mindfulness training group participated in an 8-week mindfulness-based stress reduction (MBSR) program. The control group did not take part. Regardless of the specific mindfulness practice used, low-gamma band effective connectivity increased globally after the mindfulness training. High-beta band effective connectivity increased globally only during Breathing. Moreover, relatively higher outgoing effective connectivity strength was seen during Resting and Breathing and Body-scan. By analyzing the changes in outgoing and incoming connectivity edges, both F7 and F8 exhibited strong parietal connectivity during Resting and Breathing. Multiple regression analysis revealed that the changes in effective connectivity of the right lateral prefrontal area predicted mindfulness and emotional regulation abilities. These results partially support the theory that the lateral prefrontal areas have top-down modulatory control, as these areas have high outflow effective connectivity, implying that mindfulness training cultivates better emotional regulation.
Subject(s)
Emotional Regulation , Mindfulness , Mindfulness/methods , Brain/physiology , Electroencephalography , Multivariate AnalysisABSTRACT
Uromodulin (Umod, Tamm-Horsfall protein) is the most abundant urinary N-glycoprotein produced exclusively by the kidney. It can form filaments to antagonize the adhesion of uropathogens. However, the site-specific N-glycosylation signatures of Umod in healthy individuals and patients with IgA nephropathy (IgAN) remain poorly understood due to the lack of suitable isolation and analytical methods. In this study, we first presented a simple and fast method based on diatomaceous earth adsorption to isolate Umod. These isolated glycoproteins were digested by trypsin and/or Glu-C. Intact N-glycopeptides with or without HILIC enrichment were analyzed using our developed EThcD-sceHCD-MS/MS. Based on the optimized workflow, we identified a total of 780 unique intact N-glycopeptides (7 N-glycosites and 152 N-glycan compositions) from healthy individuals. As anticipated, these glycosites exhibited glycoform heterogeneity. Almost all N-glycosites were modified completely by the complex type, except for one N-glycosite (N275), which was nearly entirely occupied by the high-mannose type for mediating Umod's antiadhesive activity. Then, we compared the N-glycosylation of Umod between healthy controls (n = 9) and IgAN patients (n = 9). The N-glycosylation of Umod in IgAN patients will drastically decrease and be lost. Finally, we profiled the most comprehensive site-specific N-glycosylation map of Umod and revealed its alterations in IgAN patients. Our method provides a high-throughput workflow for characterizing the N-glycosylation of Umod, which can aid in understanding its roles in physiology and pathology, as well as serving as a potential diagnostic tool for evolution of renal tubular function.
ABSTRACT
OBJECTIVE: To compare the outcome of using a double J (DJ) stent combined with pyelostomy tube with a DJ stent alone in laparoscopic pyeloplasty (LP) for pediatric ureteropelvic junction obstruction (UPJO). METHODS: A retrospective review of all patients with UPJO treated with LP between January 2017 and November 2021 was conducted in our center. According to different postoperative drainage methods patients were divided into a DJ stent group (52 cases) and a DJ stent combined with pyelostomy tube group (combination group, 41 cases). Operative time, bleeding volume, perirenal drainage stent removal time, postoperative hospital stay, postoperative complications, and renal function recovery were compared between the two groups. Renal ultrasound and diuretic renogram (DR) were used for preoperative and postoperative follow-up. RESULTS: A total of 52 patients were in the DJ stent group and 41 patients in the combination group. The mean hospital stay was 6.46 ± 2.66 days in the DJ stent group and 5.22 ± 1.63 days in the combination group (p < 0.05). Postoperative complications developed in 14 out of 52 patients in the DJ stent group (26.9%), while complications developed in 8 out of 41 patients in the combination group (19.5%) (p > 0.05). Non-catheter-related complications developed in 10/52 patients in the DJ stent group (19.2%) and only 1/41 patients in the combination group (2.4%) (p < 0.05). The renal function and renal cortex thickness in both groups were improved. CONCLUSION: Both the DJ stent drainage and the DJ stent combined with pyelostomy drainage are safe and effective. We should fully consider the patient's preoperative and intraoperative conditions and choose appropriate drainage methods. A DJ stent combined with pyelostomy tube can reduce non-catheter related complications, facilitate postoperative recovery, and the hospital stay was significantly shorter than the DJ stent group. However, it is necessary to pay attention to the nursing treatment of the pyelostomy tube and guard against the occurrence of pyelostomy tube shedding.
Subject(s)
Laparoscopy , Ureteral Obstruction , Child , Humans , Kidney Pelvis/surgery , Laparoscopy/methods , Urologic Surgical Procedures/methods , Kidney/physiology , Ureteral Obstruction/surgery , Nephrotomy , Retrospective Studies , Stents , Postoperative Complications/epidemiology , Postoperative Complications/surgery , Treatment OutcomeABSTRACT
BACKGROUND/AIMS: Myocardial ischemia-reperfusion injury leads to aggravated cardiac remodeling and heart failure. After myocardial infarction (MI), angiogenesis plays a vital role in the repair and regeneration of tissue. The purpose of the current study was to determine the effect of Tanshinone IIA (Tan IIA) on angiogenesis and elucidate its related mechanism. METHODS: The C57BL/6 mice MI model was established to evaluate the therapeutic effect of Tan IIA in vivo. MicroRNA (miRNA) microarray and bioinformatics analysis were performed to determine the differential expressions of miRNAs after Tan IIA administration. Cell proliferation, migration, and angiogenesis capacity were detected by EdU, Transwell, and Tube formation assay in vitro, respectively. The relationship between miR-499-5p (miR-499) and paired phosphate and tension homolog deleted on chromosome ten (PTEN) was confirmed by using a Dual-luciferase reporter assay. RESULTS: Our results showed that Tan IIA administration improved cardiac function after MI by activating angiogenesis. Further miRNA microarray and bioinformatics analysis revealed that miR-499 was significantly down-regulated, while PTEN was remarkably upregulated after Tan IIA administration post-MI. In addition, we found that miR-499 knock-down effectively promotes cell proliferation, migration, and tube formation ability of HUVECs. Dual-luciferase reporter assay demonstrated that PTEN contains a direct binding site for miR-499-5p. CONCLUSION: Tan IIA improves cardiac function post-MI by inducing angiogenesis. In terms of the mechanism, Tan IIA promotes therapeutic angiogenesis by regulating miR-499-5p/PTEN signaling pathway.
Subject(s)
MicroRNAs , Myocardial Infarction , Myocardial Reperfusion Injury , Neovascularization, Physiologic , PTEN Phosphohydrolase , Abietanes/pharmacology , Abietanes/therapeutic use , Animals , Cardiovascular Agents/pharmacology , Cardiovascular Agents/therapeutic use , Disease Models, Animal , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , MicroRNAs/metabolism , Myocardial Infarction/drug therapy , Myocardial Infarction/genetics , Myocardial Infarction/metabolism , Myocardial Ischemia/drug therapy , Myocardial Ischemia/genetics , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/genetics , Myocardial Reperfusion Injury/metabolism , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Neovascularization, Physiologic/drug effects , Neovascularization, Physiologic/genetics , Neovascularization, Physiologic/physiology , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolismABSTRACT
Consciousness is a mental characteristic of the human mind, whose exact neural features remain unclear. We aimed to identify the critical nodes within the brain's global functional network that support consciousness. To that end, we collected a large fMRI resting state dataset with subjects in at least one of the following three consciousness states: preserved (including the healthy awake state, and patients with a brain injury history (BI) that is fully conscious), reduced (including the N1-sleep state, and minimally conscious state), and lost (including the N3-sleep state, anesthesia, and unresponsive wakefulness state). We also included a unique dataset of subjects in rapid eye movement sleep state (REM-sleep) to test for the presence of consciousness with minimum movements and sensory input. To identify critical nodes, i.e., hubs, within the brain's global functional network, we used a graph-theoretical measure of degree centrality conjoined with ROI-based functional connectivity. Using these methods, we identified various higher-order sensory and motor regions including the supplementary motor area, bilateral supramarginal gyrus (part of inferior parietal lobule), supragenual/dorsal anterior cingulate cortex, and left middle temporal gyrus, that could be important hubs whose degree centrality was significantly reduced when consciousness was reduced or absent. Additionally, we identified a sensorimotor circuit, in which the functional connectivity among these regions was significantly correlated with levels of consciousness across the different groups, and remained present in the REM-sleep group. Taken together, we demonstrated that regions forming a higher-order sensorimotor integration circuit are involved in supporting consciousness within the brain's global functional network. That offers novel and more mechanism-guided treatment targets for disorders of consciousness.
Subject(s)
Anesthesia/methods , Consciousness/physiology , Nerve Net/physiology , Sensorimotor Cortex/physiology , Sleep, REM/physiology , Wakefulness/physiology , Adult , Anesthetics, Intravenous/administration & dosage , Consciousness/drug effects , Electroencephalography/methods , Female , Humans , Magnetic Resonance Imaging/methods , Male , Nerve Net/diagnostic imaging , Nerve Net/drug effects , Sensorimotor Cortex/diagnostic imaging , Sensorimotor Cortex/drug effects , Sleep, REM/drug effects , Wakefulness/drug effects , Young AdultABSTRACT
Bereavement, the experience of losing a loved one, is one of the most catastrophic but inevitable events in life. It causes grief and intense depression-like sadness. Recent studies have revealed the effectiveness and proficiency of mindfulness-based cognitive therapy (MBCT) in emotional regulation among bereavement populations. MBCT improves the well-being of the bereaved by enhancing cognitive performances. Regarding the neural correlates of bereavement grief, previous studies focused on the alleviation of emotion-cognition interferences at specific brain regions. Here, we hypothesized that the bereavement grief fundamentally triggers global alterations in the resting-state brain networks and part of the internetwork connectivity could be reformed after MBCT intervention. We recruited 19 bereaved individuals who participated the 8-week MBCT program. We evaluated (a) the large-scale changes in brain connectivity affected by the MBCT program; as well as (b) the association between connectivity changes and self-rated questionnaire. First, after MBCT, the bereaved individuals showed the reduction of the internetwork connectivity in the salience, default-mode and fronto-parietal networks in the resting state but not under emotional arousal, implying the alleviated attention to spontaneous mind wandering after MBCT. Second, the alterations of functional connectivity between subcortical (e.g., caudate) and cortical networks (e.g., cingulo-opercular/sensorimotor) were associated with the changes of the mindfulness scale, the anxiety and the emotion regulation ability. In summary, MBCT could enhance spontaneous emotion regulation among the bereaved individuals through the internetwork reorganizations in the resting state.
Subject(s)
Anxiety/diagnostic imaging , Bereavement , Brain/diagnostic imaging , Cognitive Behavioral Therapy/methods , Mindfulness/methods , Nerve Net/diagnostic imaging , Adult , Aged , Anxiety/psychology , Anxiety/therapy , Brain/physiology , Female , Grief , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Nerve Net/physiology , Prospective Studies , Rest/physiologyABSTRACT
Immunoglobulin G (IgG) molecules modulate an immune response. However, site-specific N-glycosylation signatures of plasma IgG in patients with chronic kidney disease (CKD) remain unclear. This study aimed to propose a novel method to explore the N-glycosylation pattern of IgG and to compare it with reported methods. We separated human plasma IgG from 58 healthy controls (HC) and 111 patients with CKD. Purified IgG molecules were digested by trypsin. Tryptic peptides without enrichment of intact N-glycopeptides were analyzed using a combination of electron-transfer/higher-energy collisional dissociation (EThcD) and stepped collision energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (EThcD-sceHCD-MS/MS). This resulted in higher spectral quality, more informative fragment ions, higher Byonic score, and nearly twice the depth of intact N-glycopeptide identification than sceHCD or EThcD alone. Site-specific N-glycosylation mapping revealed that intact N-glycopeptides were differentially expressed in HC and CKD patients; thus, it can be a diagnostic tool. This study provides a method for the determination of glycosylation patterns in CKD and a framework for understanding the role of IgG in the pathophysiology of CKD. Data are available via ProteomeXchange with identifier PXD027174.
Subject(s)
Renal Insufficiency, Chronic , Tandem Mass Spectrometry , Glycopeptides , Humans , Immunoglobulin G , Renal Insufficiency, Chronic/diagnosis , Systems AnalysisABSTRACT
Despite of the good stability with Li-metal, Li6.75 La3 Zr1.75 Ta0.25 O12 (LLZTO) suffers from large interfacial resistance and severe Li-metal penetration. Herein, a dual layer ceramic electrolyte of Ti-doped LLZTO(Ti-LLZTO)/LLZTO was developed, with the reducible Ti-LLZTO layer contacting Li-metal and the LLZTO layer contacting cathode. The identical crystal structures of Ti-LLZTO and LLZTO enables a seamless contact and a barrierless Li+ transport between them. The densities of Ti-LLZTO pellets are higher than that of LLZTO. With an inâ situ reduction of Ti-LLZTO by Li-metal, the interfacial wettability was improved and a mixed ion-electron conducting layer was created. Both features help to reduce defects/pores on interface and homogenize the interfacial ionic/electronic flux, facilitating the reduction of interfacial resistance and suppression of dendrites. With the help of Ti-LLZTO layer, long-term stable lithium plating/stripping was reached in an areal capacity of 3.0â mAh cm-2 .
ABSTRACT
PURPOSE: Resting-state functional MRI (rs-FMRI) has shown potential for presurgical mapping of eloquent cortex when a patient's performance on task-based FMRI is compromised. The seed-based analysis is a practical approach for detecting rs-FMRI functional networks; however, seed localization remains challenging for presurgical language mapping. Therefore, we proposed a data-driven approach to guide seed localization for presurgical rs-FMRI language mapping. METHODS: Twenty-six patients with brain tumors located in left perisylvian regions had undergone task-based FMRI and rs-FMRI before tumor resection. For the seed-based rs-FMRI language mapping, a seeding approach that integrates regional homogeneity and meta-analysis maps (RH+MA) was proposed to guide the seed localization. Canonical and task-based seeding approaches were used for comparison. The performance of the 3 seeding approaches was evaluated by calculating the Dice coefficients between each rs-FMRI language mapping result and the result from task-based FMRI. RESULTS: With the RH+MA approach, selecting among the top 6 seed candidates resulted in the highest Dice coefficient for 81% of patients (21 of 26) and the top 9 seed candidates for 92% of patients (24 of 26). The RH+MA approach yielded rs-FMRI language mapping results that were in greater agreement with the results of task-based FMRI, with significantly higher Dice coefficients (P < .05) than that of canonical and task-based approaches within putative language regions. CONCLUSION: The proposed RH+MA approach outperformed the canonical and task-based seed localization for rs-FMRI language mapping. The results suggest that RH+MA is a robust and feasible method for seed-based functional connectivity mapping in clinical practice.
Subject(s)
Brain Neoplasms , Language , Brain Mapping , Brain Neoplasms/diagnostic imaging , Cerebral Cortex , Humans , Magnetic Resonance ImagingABSTRACT
Nonrapid eye movement (NREM) sleep is associated with fading consciousness in humans. Recent neuroimaging studies have demonstrated the spatiotemporal alterations of the brain functional connectivity (FC) in NREM sleep, suggesting the changes of information integration in the sleeping brain. However, the common stationarity assumption in FC does not satisfactorily explain the dynamic process of information integration during sleep. The dynamic FC (dFC) across brain networks is speculated to better reflect the time-varying information propagation during sleep. Accordingly, we conducted simultaneous EEG-fMRI recordings involving 12 healthy men during sleep and observed dFC across sleep stages using the sliding-window approach. We divided dFC into two aspects: mean dFC (dFCmean ) and variance dFC (dFCvar ). A high dFCmean indicates stable brain network integrity, whereas a high dFCvar indicates instability of information transfer within and between functional networks. For the network-based dFC, the dFCvar were negatively correlated with the dFCmean across the waking and three NREM sleep stages. As sleep deepened, the dFCmean decreased (N0~N1 > N2 > N3), whereas the dFCvar peaked during the N2 stage (N0~N1 < N3 < N2). The highest dFCvar during the N2 stage indicated the unstable synchronizations across the entire brain. In the N3 stage, the overall disrupted network integration was observed through the lowest dFCmean and elevated dFCvar, compared with N0 and N1. Conclusively, when the network specificity (dFCmean ) breaks down, the consciousness dissipates with increasing variability of information exchange (dFCvar ).
Subject(s)
Brain/diagnostic imaging , Consciousness/physiology , Nerve Net/diagnostic imaging , Sleep Stages/physiology , Adult , Brain/physiology , Brain Mapping , Electroencephalography , Female , Humans , Magnetic Resonance Imaging , Male , Nerve Net/physiology , Neural Pathways/diagnostic imaging , Neural Pathways/physiology , Young AdultABSTRACT
Rapid eye movement (REM) sleep has been frequently associated with dreaming. However, mounting evidence obtained from behavioral, pharmacological, and brain imaging studies suggests that REM sleep is not indicative of the dream report and may originate from diverse neural substrates in brain functionality. The aim of the current study was to investigate the functional systems associated with inter-individual differences in dream recall and REM sleep through assessments of the resting-state functional connectivity. We collected resting-state functional magnetic resonance imaging (fMRI) data for functional connectivity evaluations from 43 healthy adult volunteers (23 men) before and after sleep. For assessment of the dream recall frequency, a 2-week sleep diary was maintained by all volunteers. In addition, whole-night polysomnography was performed for measuring the REM sleep percentage. Voxel-wise correlation analyses of 12 functional connectivity networks of interest with the dream recall frequency and REM sleep percentage were conducted using general linear model analysis. Both the dream recall frequency and REM sleep percentage showed negative associations with multiple brain functional networks. However, the dream recall frequency was mainly related to functional connectivity within the lateral visual network and thalamus, whereas the REM sleep percentage was mainly associated with connectivity within the frontoparietal networks and cerebellum. In addition, the dream recall frequency showed stronger coupling with the lateral visual network connectivity at night, whereas the coupling between the REM sleep percentage and cerebellum was higher in the morning. This indicated a significant time of day effect. Our results provide neuroimaging evidence that the functional system associated with the dream recall frequency is different from that associated with the REM sleep percentage.
Subject(s)
Brain/physiology , Dreams/physiology , Mental Recall/physiology , Sleep, REM , Adult , Brain Mapping , Female , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/physiology , Polysomnography , Young AdultABSTRACT
BACKGROUND: The worldwide prevalence of obesity is increasing. Obesity is associated with a variety of chronic diseases, including chronic kidney disease. Several studies suggested that body mass index (BMI) could be an independent risk factor for progression of IgA nephropathy (IgAN). However, whether high BMI is associated with progression of IgAN remains uncertain. METHODS: This retrospective study included patients with biopsy proven IgAN from 2006 to 2017 in Sichuan Provincial People's Hospital. BMI was categorized according to the WHO Asian guideline: underweight (< 18.5 kg/m2), normal weight (18.5-25 kg/m2), overweight (25-28 kg/m2) and obese (≥28 kg/m2). The main outcome was development of end-stage renal disease (ESRD) or a decline in eGFR by at least 30%. The association of BMI and IgAN progression was determined by propensity-score-matched cohort analysis. RESULTS: Four hundred eighty one patients with IgAN were finally enrolled in this study. The mean age was 37 ± 11 years and 40.3% were men. There was no significant difference in clinical and pathological characteristics among the four-group patients categorized by BMI. After matching with propensity scores, no significant correlation between BMI and renal outcomes was seen. However, compared with the reference group (18.5â¦BMIâ¦25 kg/m2), being overweight (odd ratio [OR], 2.28; 95%CI: 1.06-4.88; P = 0.034) and obese (OR, 3.43; 95%CI: 1.06-11.04; P = 0.039) was associated with a high risk of interstitial fibrosis. In the cross figure demonstrating the association of BMI subgroup and interstitial fibrosis on renal outcomes, ORs of interstitial fibrosis groups were higher than those of no interstitial fibrosis. Compared with other BMI subgroups, patients with 18.5-25 kg/m2 had lowest ORs. CONCLUSIONS: High BMI and interstitial fibrosis were associated with progression of IgAN. Interstitial fibrosis appears to be common in IgAN patients with elevated BMI.
Subject(s)
Body Mass Index , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/pathology , Kidney/pathology , Obesity/complications , Thinness/complications , Adolescent , Adult , Disease Progression , Female , Fibrosis , Glomerular Filtration Rate , Glomerulonephritis, IGA/physiopathology , Humans , Ideal Body Weight , Kidney Failure, Chronic/etiology , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Peritoneal dialysis (PD) is one of the important treatment strategies for end stage renal disease (ESRD). In this study, we aimed to study the patients on PD of Sichuan province in the registry system and to explore the risk factors. METHODS: This was a retrospective study based on data from the Chinese National Renal Data System (CNRDS). The outcomes were prevalence and incidence of patients receiving PD, all-cause mortality, technical failure, end events and peritonitis. RESULTS: This study included 2654 patients between 1 January 2010 and 31 December 2016. From 2010 to 2016, despite there were increasing numbers of patients requiring PD. Primary and secondary glomerular diseases were the main causes of ESRD. Erythropoietin, iron and antihypertensive agents were the most commonly used medications in this cohort. 12.43% of patients died and the most important cause of death was cardiac events (30.30%). The incidences of peritonitis were 0.09, 0.16, 0.11, 0.09, 0.08, 0.12 and 0.06 per patient-year, respectively. The most common etiological agent of peritonitis was staphylococcus. We divided the patients into four groups according to the incident months of peritonitis. Compared with <20 months group, the level of calcium and platelet in >60 months group were higher, and the level of ferritin in >60 months group was lower. CONCLUSION: Our results, representing the first largest report of peritoneal dialysis in the Southwest of China, indicated increasing numbers of patients receiving peritoneal dialysis, which will require need for medical resource.
Subject(s)
Kidney Failure, Chronic/mortality , Peritoneal Dialysis , Peritonitis/epidemiology , Adult , Age Distribution , Aged , Cause of Death , China/epidemiology , Female , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Peritonitis/etiology , Registries , Retrospective Studies , Risk Factors , Sex Distribution , Time Factors , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: THSD7A is a new target antigen of idiopathic membranous nephropathy (IMN). Moreover, malignancies are also found in patients with THSD7A-positive membranous nephropathy. We aimed to systematically evaluate the prevalence of THSD7A in IMN patients and malignancies in THSD7A-positive patients. METHODS: We searched English and Chinese database to 31 December 2017 with the term 'THSD7A' or 'thrombospondin type 1 domain-containing 7A'. Meta-analysis was used to explore the positive rate of THSD7A in the IMN patients. Subgroup analysis was performed according to the race, sample size, and detecting method of THSD7A. RESULTS: Ten studies involving 4121 participants were eventually included. The prevalence of THSD7A was 3% (95% CI, 3%-4%) in all patients and 10% (95% CI, 6%-15%) in PLA2R-negative patients. 77 patients had positive circulating antibodies, and the prevalence of THSD7A was also low at 3% (95% CI, 2%-4%). Overall, 72 patients had positive THSD7A staining on renal biopsy, and the prevalence was 3% (95% CI 2%-4%). Subgroup analysis showed significant differences in the prevalence of THSD7A based on the study sample sizes, however, no significant differences were seen in different ethnic groups. Furthermore, among THSD7A-positive patients, 3/10 studies reported malignancies with the incidence varied from 6% to 25%. CONCLUSIONS: The prevalence of THSD7A is more common in the PLA2R-negative patients than the IMN patients. Screening for malignancies in THSD7A-positive MN patients is recommended.
Subject(s)
Autoantibodies/blood , Glomerulonephritis, Membranous/diagnosis , Kidney Neoplasms/epidemiology , Thrombospondins/blood , Autoantibodies/immunology , Autoantigens/immunology , Biopsy , Glomerulonephritis, Membranous/blood , Glomerulonephritis, Membranous/immunology , Glomerulonephritis, Membranous/pathology , Humans , Incidence , Kidney Glomerulus/immunology , Kidney Glomerulus/pathology , Kidney Neoplasms/blood , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology , Prevalence , Receptors, Phospholipase A2/metabolism , Thrombospondins/immunologyABSTRACT
The effectiveness of pulsed thermography (PT) for detecting delamination in carbon fiber-reinforced polymer (CFRP) plates has been widely verified. However, delaminations are usually characterized by weak visibility due to the influences of inspection factors and the delaminations with weak visibility are easily missed in real inspections. In this study, by introducing a deep learning algorithm-stacked autoencoder (SAE)-to PT, we propose a novel approach (SAE-PT) to enhance the visibility of delaminations. Based on the ability of SAE to learn unsupervised features from data, the thermal features of delaminations are extracted from the raw thermograms. The extracted features are then employed to construct SAE images, in which the visibility of delaminations is expected to be enhanced. To test the performance of SAE-PT, we inspected CFRP plates with prefabricated delaminations. By implementing SAE-PT on the raw inspection data, the delaminations were more clearly indicated in the constructed SAE images. We also compare SAE-PT to the widely used principal component thermography (PCT) method to further verify the validity of the proposed approach. The results reveal that compared to PCT, SAE-PT can show delaminations in CFRP with higher contrast. By effectively enhancing the delamination visibility, SAE-PT thus has potential for improving the inspection accuracy of PT for non-destructive testing (NDT) of CFRP.
ABSTRACT
PURPOSE: To evaluate the age effect on working memory (WM) performance and functional activation after mild traumatic brain injury (MTBI). MATERIALS AND METHODS: This study was approved by the local research ethics committee. All participants provided written informed consent. N-back WM cerebral activation was assessed with functional magnetic resonance (MR) imaging in 13 younger (mean age, 26.2 years ± 2.9; range, 21-30 years) and 13 older (mean age, 57.8 years ± 6.6; range, 51-68 years) patients with MTBI and 26 age- and sex-matched control subjects. Two functional MR images were obtained within 1 month after injury and 6 weeks after the initial study. Group comparison and regression analysis were performed among postconcussion symptoms, neuropsychologic tests, and WM activity in both groups. RESULTS: In younger patients, initial hyperactivation was seen in the right precuneus and right inferior parietal gyrus (P = .047 and P = .025, respectively) in two-back greater than one-back conditions compared with younger control subjects, whereas in older patients, hypoactivation was seen in the right precuneus and right inferior frontal gyrus (P = .013 and P =.019, respectively) compared with older control subjects. Increased WM activity was associated with increased postconcussion symptoms in the right precuneus (r = 0.57; P = .026) and right inferior frontal gyrus (r = 0.60; P = .019) and poor WM performance in the right precuneus (r = -0.55; P = .027) in younger patients at initial studies but not in older patients. At follow-up examinations, partial recovery of activation pattern and decreased postconcussion symptoms (P = .04) were observed in younger patients but not in older patients. CONCLUSION: The different manifestations of postconcussion symptoms at functional MR imaging between younger and older patients confirmed the important role of age in the activation, modulation, and allocation of WM processing resources after MTBI. These findings also supported that younger patients have better neural plasticity and clinical recovery than do older patients.