Single-cell RNA-seq reveals cellular heterogeneity from deep fascia in patients with acute compartment syndrome

IntroductionHigh stress in the compartment surrounded by the deep fascia can cause acute compartment syndrome (ACS) that may result in necrosis of the limbs. The study aims to investigate the cellular heterogeneity of the deep fascia in ACS patients by single-cell RNA sequencing (scRNA-seq).MethodsWe collected deep fascia samples from patients with ACS (high-stress group, HG, n=3) and patients receiving thigh amputation due to osteosarcoma (normal-stress group, NG, n=3). We utilized ultrasound and scanning electron microscopy to observe the morphologic change of the deep fascia, used multiplex staining and multispectral imaging to explore immune cell infiltration, and applied scRNA-seq to investigate the cellular heterogeneity of the deep fascia and to identify differentially expressed genes.ResultsNotably, we identified GZMK+interferon-act CD4 central memory T cells as a specific high-stress compartment subcluster expressing interferon-related genes. Additionally, the changes in the proportions of inflammation-related subclusters, such as the increased proportion of M2 macrophages and decreased proportion of M1 macrophages, may play crucial roles in the balance of pro-inflammatory and anti-inflammatory in the development of ACS. Furthermore, we found that heat shock protein genes were highly expressed but metal ion-related genes (S100 family and metallothionein family) were down-regulated in various subpopulations under high stress.ConclusionsWe identified a high stress-specific subcluster and variations in immune cells and fibroblast subclusters, as well as their differentially expressed genes, in ACS patients. Our findings reveal the functions of the deep fascia in the pathophysiology of ACS, providing new approaches for its treatment and prevention

Association between sleep duration and quality with rapid kidney function decline and development of chronic kidney diseases in adults with normal kidney function: The China health and retirement longitudinal study

Research have shown that sleep is associated with renal function. However, the potential effects of sleep duration or quality on kidney function in middle-aged and older Chinese adults with normal kidney function has rarely been studied. Our study aimed to investigate the association of sleep and kidney function in middle-aged and older Chinese adults. Four thousand and eighty six participants with an eGFR ≥60 ml/min/1.73 m2 at baseline were enrolled between 2011 and 2015 from the China Health and Retirement Longitudinal Study. Survey questionnaire data were collected from conducted interviews in the 2011. The eGFR was estimated from serum creatinine and/or cystatin C using the Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI). The primary outcome was defined as rapid kidney function decline. Secondary outcome was defined as rapid kidney function decline with clinical eGFR of <60 ml/min/1.73 m2 at the exit visit. The associations between sleep duration, sleep quality and renal function decline or chronic kidney disease (CKD) were assessed based with logistic regression model. Our results showed that 244 (6.0%) participants developed rapid decline in kidney function, while 102 (2.5%) developed CKD. In addition, participants who had 3–7 days of poor sleep quality per week had higher risks of CKD development (OR 1.86, 95% CI 1.24–2.80). However, compared with those who had 6–8 h of night-time sleep, no significantly higher risks of rapid decline in kidney function was found among those who had <6 h or >8 h of night time sleep after adjustments for demographic, clinical, or psychosocial covariates. Furthermore, daytime nap did not present significant risk in both rapid eGFR decline or CKD development. In conclusion, sleep quality was significantly associated with the development of CKD in middle-aged and older Chinese adults with normal kidney function

Research on an online self-organizing radial basis function neural network

A new growing and pruning algorithm is proposed for radial basis function (RBF) neural network structure design in this paper, which is named as self-organizing RBF (SORBF). The structure of the RBF neural network is introduced in this paper first, and then the growing and pruning algorithm is used to design the structure of the RBF neural network automatically. The growing and pruning approach is based on the radius of the receptive field of the RBF nodes. Meanwhile, the parameters adjusting algorithms are proposed for the whole RBF neural network. The performance of the proposed method is evaluated through functions approximation and dynamic system identification. Then, the method is used to capture the biochemical oxygen demand (BOD) concentration in a wastewater treatment system. Experimental results show that the proposed method is efficient for network structure optimization, and it achieves better performance than some of the existing algorithms

Design of Deep Belief Networks for Short-Term Prediction of Drought Index Using Data in the Huaihe River Basin

With the global climate change, drought disasters occur frequently. Drought prediction is an important content for drought disaster management, planning and management of water resource systems of a river basin. In this study, a short-term drought prediction model based on deep belief networks (DBNs) is proposed to predict the time series of different time-scale standardized precipitation index (SPI). The DBN model is applied to predict the drought time series in the Huaihe River Basin, China. Compared with BP neural network, the DBN-based drought prediction model has shown better predictive skills than the BP neural network for the different time-scale SPI. This research can improve drought prediction technology and be helpful for water resources managers and decision makers in managing drought disasters

Lipopolysaccharide and palmitic acid synergistically induced MCP-1 production via MAPK-meditated TLR4 signaling pathway in RAW264.7 cells

Abstract Background Obesity increases the risk of developing diabetes mellitus. Clinical studies suggest that risk factors like palmitic acid (PA) and lipopolysaccharide (LPS) exist simultaneously in diabetes with obesity. Combination of PA and LPS even at low concentration can induce strong inflammatory reaction. Monocyte chemoattractant protein-1 (MCP-1) is an important inflammatory chemokine related to insulin resistance and type II diabetes. Our previous study using PCR array revealed that LPS and PA synergistically induce MCP-1 mRNA expression in macrophage cells RAW264.7, while the protein expression of MCP-1 in this case was not investigated. Moreover, the underling mechanism in the synergistic effect of MCP-1 expression or production induced by treatment of LPS and PA combination remains unclear. Methods Protein secretion of MCP-1 was measured by the enzyme-linked immunosorbent assay (ELISA) and mRNA levels of MCP-1 and Toll-like receptor 4 (TLR4) were measured by real-time PCR. Statistical analysis was conducted using SPSS software. Results LPS could increase MCP-1 transcription as well as secretion in RAW264.7, and PA amplified this effect obviously. Meanwhile, combination of LPS with PA increased TLR4 mRNA expression while LPS alone or PA alone could not, TLR4 knockdown inhibited MCP-1 transcription/secretion induced by LPS plus PA. Moreover, not NF-κB inhibitor but inhibitors of mitogen-activated protein kinase (MAPK) signaling pathways, including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPK were found to block MCP-1 generation stimulated by LPS plus PA. Conclusion LPS and PA synergistically induced MCP-1 secretion in RAW264.7 macrophage cells, in which MCP-1 transcription mediated by MAPK/TLR4 signaling pathways was involved. Combined treatment of PA and LPS in RAW264.7 cells mimics the situation of diabetes with obesity that has higher level of PA and LPS, MAPK/TLR4/ MCP-1 might be potential therapeutic targets for diabetes with obesity

Clinical Effects of the Probing Method with Depth Gauge for Determining the Screw Depth of Locking Proximal Humeral Plate

Background. The use of locking plates has gained popularity to treat proximal humeral fractures. However, the complication rates remain high. Biomechanical study suggested that subchondral screw-tip abutment significantly increased the stability of plant. We present a simple method to obtain the proper screw length through the depth gauge in elderly patients and compared the clinical effects with traditional measuring method. Methods. 40 patients were separated into two groups according to the two surgical methods: the probing method with depth gauge and the traditional measuring method. The intraoperative indexes and postoperative complications were recorded. The Constant and Murley score was used for the functional assessment in the 12th month. Results. Operative time and intraoperative blood loss indicated no statistical differences. X-ray exposure time and the patients with screw path penetrating the articular cartilage significantly differed. Postoperative complications and Constant and Murley score showed no statistical differences. Conclusions. Probing method with depth gauge is an appropriate alternative to determine the screw length, which can make the screw-tip adjoin the subchondral bone and keep the articular surface of humeral head intact and at the same time effectively avoid frequent X-ray fluoroscopy and adjusting the screws

Docosahexaenoic acid antagonizes the boosting effect of palmitic acid on LPS inflammatory signaling by inhibiting gene transcription and ceramide synthesis.

It is well known that saturated fatty acids (SFAs) and unsaturated fatty acid, in particular omega-3 polyunsaturated fatty acids (n-3 PUFAs), have different effects on inflammatory signaling: SFAs are pro-inflammatory but n-3 PUFAs have strong anti-inflammatory properties. We have reported that palmitic acid (PA), a saturated fatty acid, robustly amplifies lipopolysaccharide (LPS) signaling to upregulate proinflammatory gene expression in macrophages. We also reported that the increased production of ceramide (CER) via sphingomyelin (SM) hydrolysis and CER de novo synthesis plays a key role in the synergistic effect of LPS and PA on proinflammatory gene expression. However, it remains unclear if n-3 PUFAs are capable of antagonizing the synergistic effect of LPS and PA on gene expression and CER production. In this study, we employed the above macrophage culture system and lipidomical analysis to assess the effect of n-3 PUFAs on proinflammatory gene expression and CER production stimulated by LPS and PA. Results showed that DHA strongly inhibited the synergistic effect of LPS and PA on proinflammatory gene expression by targeting nuclear factor kappa B (NFκB)-dependent gene transcription. Results also showed that DHA inhibited the cooperative effect of LPS and PA on CER production by targeting CER de novo synthesis, but not SM hydrolysis. Furthermore, results showed that myriocin, a specific inhibitor of serine palmitoyltransferase, strongly inhibited both LPS-PA-stimulated CER synthesis and proinflammatory gene expression, indicating that CER synthesis is associated with proinflammatory gene expression and that inhibition of CER synthesis contributes to DHA-inhibited proinflammatory gene expression. Taken together, this study demonstrates that DHA antagonizes the boosting effect of PA on LPS signaling on proinflammatory gene expression by targeting both NFκB-dependent transcription and CER de novo synthesis in macrophages