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The dry skin tortures numerous patients with severe itch. The transient receptor potential cation channel V member 1 (TRPV1) and A member 1 (TRPA1) are two essential receptors for peripheral neural coding of itch sensory, mediating histaminergic and nonhistaminergic itch separately. In the dorsal root ganglion, transmembrane protein 100 (TMEM100) is structurally related to both TRPV1 and TRPA1 receptors, but the exact role of TMEM100 in itch sensory coding is still unknown. Here, in this study, we find that TMEM100 + DRG neurons account for the majority of activated neurons in an acetone-ether-water (AEW)-induced dry skin itch model, and some TMEM100 + DRG neurons are colocalized with both TRPA1 and the chloroquine-related Mrgpr itch receptor family. Both the expression and function of TRPA1 channels, but not TRPV1 channels, are upregulated in the AEW model, and specific DRG Tmem100 gene knockdown alleviates AEW-induced itch and rescues the expression and functional changes of TRPA1. Our results strongly suggest that TMEM100 protein in DRG is the main facilitating factor for dry skin-related chronic itch, and specific suppression of TMEM100 in DRG could be a novel effective treatment strategy for patients who suffer from dry skin-induced itch.

Hepatocyte-derived liver progenitor-like cells (HepLPCs) exhibit a remarkable capacity to support liver function by detoxifying ammonia, promoting native liver regeneration, and suppressing inflammation, which leads to improvements in the recovery and survival of animals with acute liver failure (ALF). However, the mechanism through which HepLPCs promote liver regeneration is unclear. Here, we isolated HepLPC-derived extracellular vesicles (HepLPC-EVs) from conditioned media and performed microRNA sequencing analysis. Our results showed HepLPC-EVs promoted liver regeneration in mice with carbon tetrachloride or acetaminophen induced ALF. Cell cycle progression and proliferation of primary human hepatocytes were promoted after coculture with HepLPC-EVs. Exosomal miRNA sequencing confirmed that HepLPC-EVs were enriched with miR-183-5p, which played an essential role in ameliorating ALF. Mechanistically, HepLPC-derived exosomal miR-183-5p negatively regulated the expression of the target gene FoxO1, activated the Akt/GSK3β/β-catenin signaling pathway, and thereby promoted liver regeneration and restoration of normal liver function. These results indicate that during ALF, HepLPC-Exos mediate liver regeneration mainly through a paracrine exosome-dependent mechanism and these effects accelerate liver regeneration and lead to the restoration of normal liver function. [ABSTRACT FROM AUTHOR]

The rostral ventromedial medulla (RVM) exerts bidirectional descending modulation of pain attributable to the activity of electrophysiologically identified pronociceptive ON and antinociceptive OFF neurons. Here, we report that GABAergic ON neurons specifically express G protein-coupled estrogen receptor (GPER). [GPER.sup.+] neurons exhibited characteristic ON-like responses upon peripheral nociceptive stimulation. Optogenetic activation of [GPER.sup.+] neurons facilitated, but their ablation abrogated, pain. Furthermore, activation of GPER caused depolarization of ON cells, potentiated pain, and ameliorated morphine analgesia through desensitizing [micro]-type opioid receptor-mediated (MOR-mediated) activation of potassium currents. In contrast, genetic ablation or pharmacological blockade of GPER attenuated pain, enhanced morphine analgesia, and delayed the development of morphine tolerance in diverse preclinical pain models. Our data strongly indicate that GPER is a marker for GABAergic ON cells and illuminate the mechanisms underlying hormonal regulation of pain and analgesia, thus highlighting GPER as a promising target for the treatment of pain and opioid tolerance., Introduction It is well known that the brain may impose powerful bidirectional descending control on the ascending transmission of pain signals and that pain sensation is ultimately determined by integrated [...]

Fetal cleft lip is a common congenital defect. Considering the delicacy and difficulty of observing fetal lips, we have utilized deep learning technology to develop a new model aimed at quickly and accurately assessing the development of fetal lips during prenatal examinations. This model can detect ultrasound images of the fetal lips and classify them, aiming to provide a more objective prediction for the development of fetal lips. This study included 632 pregnant women in their mid-pregnancy stage, who underwent ultrasound examinations of the fetal lips, collecting both normal and abnormal fetal lip ultrasound images. To improve the accuracy of the detection and classification of fetal lips, we proposed and validated the Yolov5-ECA model. The experimental results show that, compared with the currently popular 10 models, our model achieved the best results in the detection and classification of fetal lips. In terms of the detection of fetal lips, the mean average precision (mAP) at 0.5 and mAP at 0.5:0.95 were 0.920 and 0.630, respectively. In the classification of fetal lip ultrasound images, the accuracy reached 0.925. The deep learning algorithm has accuracy consistent with manual evaluation in the detection and classification process of fetal lips. This automated recognition technology can provide a powerful tool for inexperienced young doctors, helping them to accurately conduct examinations and diagnoses of fetal lips. [ABSTRACT FROM AUTHOR]

Aims: The parabrachial nucleus (PBN) promotes wakefulness states under general anesthesia. Recent studies have shown that glutamatergic neurons within the PBN play a crucial role in facilitating emergence from anesthesia. Our previous study indicates that vesicular glutamate transporter 2 (vglut2) expression neurons of the PBN extend into the extended amygdala (EA). However, the modulation of PBNvglut2‐EA in general anesthesia remains poorly understood. This study aims to investigate the role of PBNvglut2‐EA in alterations of consciousness during sevoflurane anesthesia. Methods: We first validated vglut2‐expressing neuron projections from the PBN to the EA using anterograde tracing. Then, we conducted immunofluorescence staining of c‐Fos to investigate the role of the EA involved in the regulation of consciousness during sevoflurane anesthesia. After, we performed calcium fiber photometry recordings to determine the changes in PBNvglut2‐EA activity. Lastly, we modulated PBNvglut2‐EA activity under sevoflurane anesthesia using optogenetics, and electroencephalogram (EEG) was recorded during specific optogenetic modulation. Results: The expression of vglut2 in PBN neurons projected to the EA, and c‐Fos expression in the EA was significantly reduced during sevoflurane anesthesia. Fiber photometry revealed that activity in the PBNvglut2‐EA pathway was suppressed during anesthesia induction but restored upon awakening. Optogenetic activation of the PBNvglut2‐EA delayed the induction of anesthesia. Meanwhile, EEG recordings showed significantly decreased δ oscillations and increased β and γ oscillations compared to the EYFP group. Furthermore, optogenetic activation of the PBNvglut2‐EA resulted in an acceleration of awakening from anesthesia, accompanied by decreased δ oscillations on EEG recordings. Optogenetic inhibition of PBNvglut2‐EA accelerated anesthesia induction. Surprisingly, we found a sex‐specific regulation of PBNvglut2‐EA in this study. The activity of PBNvglut2‐EA was lower in males during the induction of anesthesia and decreased more rapidly during sevoflurane anesthesia compared to females. Photoactivation of the PBNvglut2‐EA reduced the sensitivity of males to sevoflurane, showing more pronounced wakefulness behavior and EEG changes than females. Conclusions: PBNvglut2‐EA is involved in the promotion of wakefulness under sevoflurane anesthesia. Furthermore, PBNvglut2‐EA shows sex differences in the changes of consciousness induced by sevoflurane anesthesia. [ABSTRACT FROM AUTHOR]

Aim: To explore the regulatory mechanisms of microglia‐mediated cytotoxic CD8+ T‐cell infiltration in the white matter injury of perioperative stroke (PIS). Methods: Adult male C57BL/6 mice were subjected to ileocolic bowel resection (ICR) 24 h prior to permanent distant middle cerebral artery occlusion (dMCAO) to establish model PIS. White matter injury, functional outcomes, peripheral immune cell infiltration, and microglia phenotype were assessed up to 28 days after dMCAO using behavioral phenotyping, immunofluorescence staining, transmission electron microscopy, western blot, and FACS analysis. Results: We found surgery aggravated white matter injury and deteriorated sensorimotor deficits up to 28 days following PIS. The PIS mice exhibited significantly increased activation of peripheral and central CD8+ T cells, while significantly reduced numbers of mature oligodendrocytes compared to IS mice. Neutralizing CD8+ T cells partly reversed the aggravated demyelination following PIS. Pharmacological blockage or genetic deletion of receptor‐interacting protein kinase 1 (RIPK1) activity could alleviate CD8+ T‐cell infiltration and demyelination in PIS mice. Conclusion: Surgery exacerbates demyelination and worsens neurological function by promoting infiltration of CD8+ T cells and microglia necroptosis, suggesting that modulating interactions of CD8+ T cells and microglia could be a novel therapeutic target of long‐term neurological deficits of PIS. [ABSTRACT FROM AUTHOR]

The quality and standardized training and certification of young physicians is key to the quality of health care in the future. In contrast to the American system, there is no nationwide and standardized oral examination in the training and certification process for anesthesiologists in China. The adoptability of the American anesthesia oral examination in China, as well as potential roadblocks, has not been specifically discussed. In this commentary, we share our experience of introducing the American oral examination to an audience of Chinese anesthesiologists and propose a pragmatic approach for adopting the anesthesia oral examination in China. This initiative has the potential to reform the current anesthesia training and certification process and improve the quality of anesthetic care in China.

At present, prenatal ultrasound is one of the important means for screening fetal malformations. In the process of prenatal ultrasound diagnosis, the accurate recognition of fetal facial ultrasound standard plane is crucial for facial malformation detection and disease screening. Due to the dense distribution of fetal facial images, no obvious structure contour boundary, small structure area, and large area overlap in the middle of the structure detection frame, this paper regards the fetal facial standard plane and its structure recognition as a universal target detection task for the first time, and applies real‐time YOLO v5s to the fetal facial ultrasound standard plane structure detection and classification task. First, we detect the structure of a single slice, and take the structure of a slice class as the recognition object. Second, we carry out structural detection experiments on three standard planes; then, on the basis of the previous stage, the images of all parts included in the ultrasound examination of multiple fetuses were collected. In the single‐class structure detection experiment and the structure detection and classification experiment of three types of standard planes, the overall recognition effect of Precision and Recall index data is better, with Precision being 98.3% and 98.1%, and Recall being 99.3% and 98.2%, respectively. The experimental results show that the model has the ability to identify fetal facial anatomy and standard sections in different data, which can help the physician to automatically and quickly screen out the standard sections of each fetal facial ultrasound. Synopsis: By automatically identifying key anatomical structures within ultrasound images, it provides a theoretical basis for doctors to choose standard planes. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is a severe complication that can lead to fatalities in multiple trauma patients. Nevertheless, the incidence rate and early prediction of ARDS among multiple trauma patients residing in high-altitude areas remain unknown. Methods: This study included a total of 168 multiple trauma patients who received treatment at Shigatse People's Hospital Intensive Care Unit (ICU) between January 1, 2019 and December 31, 2021. The clinical characteristics of the patients and the incidence rate of ARDS were assessed. Univariable and multivariable logistic regression models were employed to identify potential risk factors for ARDS, and the predictive effects of these risk factors were analyzed. Results: In the high-altitude area, the incidence of ARDS among multiple trauma patients was 37.5% (63/168), with a hospital mortality rate of 16.1% (27/168). Injury Severity Score (ISS) and thoracic injuries were identified as significant predictors for ARDS using the logistic regression model, with an area under the curve (AUC) of 0.75 and 0.75, respectively. Furthermore, a novel predictive risk score combining ISS and thoracic injuries demonstrated improved predictive ability, achieving an AUC of 0.82. Conclusions: This study presents the incidence of ARDS in multiple trauma patients residing in the Tibetan region, and identifies two critical predictive factors along with a risk score for early prediction of ARDS. These findings have the potential to enhance clinicians' ability to accurately assess the risk of ARDS and proactively prevent its onset. [ABSTRACT FROM AUTHOR]

Aims: Itch, a common uncomfortable sensory experience, occurs frequently in inflammatory or allergic disorders. In recent years, with the discovery of itch‐specific pathways in the peripheral and central nervous system, the association between immunology and neural pathways has gradually emerged as the main mechanism of itch. Although many studies have been conducted on itch, no bibliometric analysis study focusing on this topic has been conducted. This study aimed to explore the research hotspots and trends in the itch field from a bibliometric perspective. Methods: Publications relevant to itch, published from 2003 to 2022, were retrieved from the Science Citation Index‐Expanded of Web of Science Core Collection. Publications were critically reviewed and analyzed with CiteSpace software, Vosviewer, and the bibliometric online analysis platform. Visual maps were conducted in terms of annual production, collaborating countries or institutions, productive authors, core journals, co‐cited references, and keyword bursts. Results: 2395 articles on itch that met our criteria were identified and the quantity of publications has been increasing rapidly since 2012. The USA was the most influential country. University Hospital Münster was the institution with the most publications. Gil Yosipovitch was the most prolific author. Atopic dermatitis (AD), intradermal serotonin, chronic pruritus, mechanical itch, gastrin‐releasing peptide, substance p, interleukin‐31 receptor, histamine‐induced itch, bile acid, scratching behavior, and h‐4 receptor were the top 11 clusters in co‐citation cluster analysis. Keyword burst analysis suggested that treatment, inflammation, and AD are current research hotspots. Conclusion: Global publications on itch research have increased steadily and rapidly over the past 20 years. Inflammation and AD are current research hotspots. The neuroimmunological and neuroinflammatory mechanisms of itch, as well as clinical assessment methods and therapeutic targets, will be novel research directions in the future. This study provides guidance for further itch research. [ABSTRACT FROM AUTHOR]