Effect of dexmedetomidine hydrochloride combination with conventional anesthesia on serum cortisol, inflammatory factors and cellular immunity during surgery on children with congenital anus atresia

Purpose: To study the effect of a combination of dexmedetomidine hydrochloride (DXM) and conventional anesthesia on surgical anesthesia in pediatric congenital anoplasty.Methods: Fifty children with congenital anus atresia were divided into control and study group. Both groups underwent anal angioplasty or colostomy, with the control group under conventional anesthesia, while the study group received both conventional anesthesia and DXM. Heart beat rate, arterial blood pressure, changes in oxygen saturation were recorded. Blood loss were noted. Venous blood was collected at various time points for assay of serum cortisol, IL-6, and T-lymphocyte subsets.Results: The arterial pressure and heart beat of the study group at T1 and T2 were significantly lower than those of the control group (p ˂ 0.05). Blood loss was significantly lower in the study group than in the control group (p ˂ 0.05). Serum cortisol and IL-6 levels at T1, T2 and T3 in both groups significantly increased, compared with T0, with levels in the study group significantly lower than those in the control group (p < 0.05). Values of CD3 +, CD4 + and CD4 +/CD8 + in both groups significantly decreased at T2, when compared with corresponding values at T0, while the levels in the study group were significantly lower than those in the control group (p < 0.05).Conclusion: Dexmedetomidine hydrochloride combined with conventional anesthesia is more effective than conventional anesthesia during surgery on congenital anal atresia.Keywords: Dexmedetomidine hydrochloride, Congenital anal atresia, Cortisol, IL-6, T-lymphocyte subset

Actuator and Sensor Fault Classification for Wind Turbine Systems Based on Fast Fourier Transform and Uncorrelated Multi-Linear Principal Component Analysis Techniques

In response to the high demand of the operation reliability and predictive maintenance, health monitoring and fault diagnosis and classification have been paramount for complex industrial systems (e.g., wind turbine energy systems). In this study, data-driven fault diagnosis and fault classification strategies are addressed for wind turbine energy systems under various faulty scenarios. A novel algorithm is addressed by integrating fast Fourier transform and uncorrelated multi-linear principal component analysis techniques in order to achieve effective three-dimensional space visualization for fault diagnosis and classification under a variety of actuator and sensor faulty scenarios in 4.8 MW wind turbine benchmark systems. Moreover, comparison studies are implemented by using multi-linear principal component analysis with and without fast Fourier transform, and uncorrelated multi-linear principal component analysis with and without fast Fourier transformation data pre-processing, respectively. The effectiveness of the proposed algorithm is demonstrated and validated via the wind turbine benchmark

Zinc inhibits TRPV1 to alleviate chemotherapy-induced neuropathic pain

Zinc is a transition metal that has a long history of use as an anti-inflammatory agent. It also soothes pain sensations in a number of animal models. However, the effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy remain unknown. Here we show that locally injected zinc markedly reduces neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy drug, in a TRPV1-dependent manner. Extracellularly applied zinc also inhibits the function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm. Moreover, TRPA1 is required for zinc-induced inhibition of TRPV1-mediated acute nociception. Unexpectedly, zinc transporters, but not TRPA1, are required for zinc-induced inhibition of TRPV1-dependent chronic neuropathic pain produced by paclitaxel. Together, our study demonstrates a novel mechanism underlying the analgesic effect of zinc on paclitaxel-induced neuropathic pain that relies on the function of TRPV1

Data-Driven Fault Classification for Non-Inverting Buck–Boost DC–DC Power Converters Based on Expectation Maximisation Principal Component Analysis and Support Vector Machine Approaches

Data-driven fault classification for power converter systems has been taking more into considerations in power electronics, machine drives, and electric vehicles. It is challenging to classify the different topologies of faults in the real time monitoring control systems. In this paper, a data-driven and supervised machine learning-based fault classification technique is adopted by combining and consolidating with Expectation Maximisation Principal Component Analysis (EMPCA) and Support Vector Machine (SVM) to substantiate the availability of fault classification. The proposed methodology is applied to the non-inverting Buck–Boost DC–DC power converter systems subjected to the incipient fault and serious fault, respectively. Finally, the feasibility of the approach is validated by intensive simulations and comparison studies

Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

Dopaminergic signaling plays a critical role in the nervous system, but little is known about its potential role in breast cancer and bone metabolism. A screening of ~1,000 biologically active compounds revealed that a selective agonist of dopamine receptor D1 (DRD1), A77636, inhibited proliferation of 4T1.2 mammary tumor cells as well as MDA-MB-231 breast cancer cells. Herein, we examined the effect of A77636 on bone quality using a mouse model of bone metastasis from mammary tumor. A77636 inhibited migration of cancer cells in a DRD1-dependent fashion and suppressed development of bone-resorbing osteoclasts by downregulating NFATc1 through the elevation of phosphorylation of eIF2α. In the mouse model of bone metastasis, A77636 reduced osteolytic lesions and prevented mechanical weakening of the femur and tibia. Collectively, we expect that dopaminergic signaling might provide a novel therapeutic target for breast cancer and bone metastasis

Regional and Cellular Mapping of Sortilin Immunoreactivity in Adult Human Brain

Sortilin is a member of the vacuolar protein sorting 10 protein (VPS10P) domain receptor family, which carries out signal transduction and protein transport in cells. Sortilin serves as the third, G-protein uncoupled, receptor of neurotensin that can modulate various brain functions. More recent data indicate an involvement of sortilin in mood disorders, dementia and Alzheimer-type neuropathology. However, data regarding the normal pattern of regional and cellular expression of sortilin in the human brain are not available to date. Using postmortem adult human brains free of neuropathology, the current study determined sortilin immunoreactivity (IR) across the entire brain. Sortilin IR was broadly present in the cerebrum and subcortical structures, localizing to neurons in the somatodendritic compartment, but not to glial cells. In the cerebrum, sortilin IR exhibited differential regional and laminar patterns, with pyramidal, multipolar and polymorphic neurons in cortical layers II–VI, hippocampal formation and amygdaloid complex more distinctly labeled relative to GABAergic interneurons. In the striatum and thalamus, numerous small-to-medium sized neurons showed light IR, with a small group of large sized neurons heavily labeled. In the midbrain and brainstem, sortilin IR was distinct in neurons at the relay centers of descending and ascending neuroanatomical pathways. Dopaminergic neurons in the substantia nigra, cholinergic neurons in the basal nuclei of Meynert and noradrenergic neurons in the locus coeruleus co-expressed strong sortilin IR in double immunofluorescence. In comparison, sortilin IR was weak in the olfactory bulb and cerebellar cortex, with the mitral and Purkinje cells barely visualized. A quantitative analysis was carried out in the lateral, basolateral, and basomedial nuclei of the amygdaloid complex, as well as cortical layers II–VI, which established a positive correlation between the somal size and the intensity of sortilin IR among labeled neurons. Together, the present study demonstrates a predominantly neuronal expression of sortilin in the human brain with substantial regional and cell-type variability. The enriched expression of sortilin in pyramidal, dopaminergic, noradrenergic and cholinergic neurons suggests that this protein may be particularly required for signal transduction, protein trafficking and metabolic homeostasis in populations of relatively large-sized projective neurons

Parkin Modulates ERRα/eNOS Signaling Pathway in Endothelial Cells

Background/Aims: Although a number of reports documented the important role of parkin in mitophagy, emerging evidence also indicated additional functions of parkin besides mitophagy. The present study was undertaken to investigate the role of parkin in the regulation of ERRα/eNOS pathway in endothelial cells (ECs). Methods: Mouse aortic endothelial cells (MAECs) and cardiac muscle HL-1 cells were transfected with parkin plasmid or siRNA. ERRα inhibitor XCT-790, autophagy inhibitor 3-MA and Bafilomycin A1, and caspase inhibitor Z-VAD-FMK were used to block autophagy or apoptosis. Western blotting was performed to examine the protein levels. Flow cytometry was applied to determine the cell apoptosis and ROS production. Mitochondrial membrane potential was measured using JC-1 and TMRM. Immunoprecipitation was performed to confirm the parkin effect on ERRα ubiquitination. Results: Overexpression of parkin resulted in a significant reduction of total-eNOS and p-eNOS in parallel with the downregulation of ERRα (a regulator of eNOS) protein and the enhancement of ERRα ubiquitination. To test the role of ERRα in regulating eNOS in this experimental setting, we treated ECs with ERRα inhibitor and found a decrement of total-eNOS and p-eNOS. On the contrary, overexpression of ERRα increased the levels of total-eNOS and p-eNOS. Meanwhile, parkin overexpression induced mitochondrial dysfunction and cell apoptosis in both ECs and HL-1 cells. Finally, we confirmed that the parkin effect on the regulation of eNOS was independent of the autophagy and apoptosis. Conclusion: These findings suggested that parkin overexpression downregulated eNOS possibly through the ubiquitination of ERRα in endothelial cells

Exome sequencing in fetuses with short long bones detected by ultrasonography: A retrospective cohort study

Background: Prenatal diagnosis of fetal short long bones (SLBs) was reported to be associated with skeletal dysplasias, chromosomal abnormalities, and genetic syndromes. This study aims to identify the genetic causes for fetal short long bones, and retrospectively evaluate the additional diagnostic yield of exome sequencing (ES) for short long bones following the use of conventional genetic testing.Methods: A cohort of ninety-four fetuses with sonographically identified short long bones was analyzed by trio-exome sequencing between January 2016 and June 2021. Fetuses with abnormal results of karyotype or chromosomal microarray analysis were excluded. Variants were interpreted based on ACMG/AMP guidelines. All diagnostic de novo variants were validated by Sanger sequencing.Results: Of the 94 fetuses, 38 (40.4%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in sixteen genes with 38 variants. Five fetuses (5.3%) had variant(s) of uncertain significance. Thirty-five cases (37.2%) were diagnosed as genetic skeletal dysplasias including 14 different diseases that were classified into 10 groups according to the Nosology and Classification of Genetic Skeletal Disorders. The most common disease in the cohort was achondroplasia (28.9%), followed by osteogenesis imperfecta (18.4%), thanatophoric dysplasia (10.5%), chondrogenesis (7.9%), and 3-M syndrome (5.3%). The diagnostic yield in fetuses with isolated short long bones was lower than the fetuses with non-isolated short long bones, but not reached statistical significance (27.3% vs. 44.4%; p = 0.151). Whereas, the rate in the fetuses with other skeletal abnormalities was significantly higher than those with non-skeletal abnormalities (59.4% vs. 32.5%, p = 0.023), and the diagnostic rate was significantly higher in femur length (FL) below -4SDs group compared with FL 2-4SDs below GA group (72.5% vs. 16.7%; p < 0.001). A long-term follow-up showed that outcomes for fetuses with FL 2-4SDs below GA were significantly better than those with FL below -4SDs. Additionally, fourteen (36.8%) novel short long bones-related variants were identified in the present study.Conclusion: The findings suggest that in fetuses with short long bones routine genetic tests failed to determine the underlying causes, exome sequencing could add clinically relevant information that could assist the clinical management of pregnancies. Novel pathogenic variants identified may broaden the mutation spectrum for the disorders and contributes to clinical consultation and subsequent pregnancy examination