Effects of remimazolam tosilate on gastrointestinal hormones and gastrointestinal motility in patients undergoing gastrointestinal endoscopy with sedation: a randomized control trial.

PURPOSE: To investigate the impacts of remimazolam tosilate on gastrointestinal hormones and motility in patients undergoing gastrointestinal endoscopy with sedation. METHODS: A total of 262 American Society of Anesthesiologists Physical Status I or II patients, aged 18-65 years, scheduled for gastrointestinal endoscopy with sedation, were randomly allocated into two groups (n = 131 each): the remimazolam tosilate group (Group R) and the propofol group (Group P). Patients in Group R received 0.2-0.25 mg/Kg remimazolam tosilate intravenously, while those in Group P received 1.5-2.0 mg/kg propofol intravenously. The gastrointestinal endoscopy was performed when the Modified Observer's Assessment of Alertness/Sedation scores were ≤3. The primary endpoints included the endoscopic intestinal peristalsis rating by the endoscopist; serum motilin and gastrin levels at fasting without gastrointestinal preparation (T0), before gastrointestinal endoscopy (T1), and before leaving the Post Anesthesia Care Unit (T2); and the incidences of abdominal distension during Post Anesthesia Care Unit. RESULTS: Compared with Group P, intestinal peristalsis rating was higher in Group R (P < .001); Group R showed increased motilin and gastrin levels at T2 compared with Group P (P < .01). There was a rise in motilin and gastrin levels at T1 and T2 compared with T0 and at T2 compared with T1 in both groups (P < .01). The incidence of abdominal distension was lower in Group R (P < .05). CONCLUSION: Compared with propofol used during gastrointestinal endoscopy with sedation, remimazolam tosilate mildly inhibits the serum motilin and gastrin levels, potentially facilitating the recovery of gastrointestinal motility.

Cross-Modal Consistency for Single-Modal MR Image Segmentation.

OBJECTIVE: Multi-modal magnetic resonance (MR) image segmentation is an important task in disease diagnosis and treatment, but it is usually difficult to obtain multiple modalities for a single patient in clinical applications. To address these issues, a cross-modal consistency framework is proposed for a single-modal MR image segmentation. METHODS: To enable single-modal MR image segmentation in the inference stage, a weighted cross-entropy loss and a pixel-level feature consistency loss are proposed to train the target network with the guidance of the teacher network and the auxiliary network. To fuse dual-modal MR images in the training stage, the cross-modal consistency is measured according to Dice similarity entropy loss and Dice similarity contrastive loss, so as to maximize the prediction similarity of the teacher network and the auxiliary network. To reduce the difference in image contrast between different MR images for the same organs, a contrast alignment network is proposed to align input images with different contrasts to reference images with a good contrast. RESULTS: Comprehensive experiments have been performed on a publicly available prostate dataset and an in-house pancreas dataset to verify the effectiveness of the proposed method. Compared to state-of-the-art methods, the proposed method can achieve better segmentation. CONCLUSION: The proposed image segmentation method can fuse dual-modal MR images in the training stage and only need one-modal MR images in the inference stage. SIGNIFICANCE: The proposed method can be used in routine clinical occasions when only single-modal MR image with variable contrast is available for a patient.

A single 24 h maternal separation at PND 9 promotes behavioral resilience of female C57BL/6J mice and the possible role of hippocampal Homer1a.

Early life stress (ELS) has been thought to increase vulnerability to developing psychiatric disorders later in life, while some researchers have found that adversity early in life may promote stress resilience. Studies investigating the resilient effect of maternal separation (MS) are still relatively few, and the underlying mechanisms remain unknown. In the current study, the effect of a single 24 h MS paradigm at postnatal day 9 (PND 9) in female C57BL/6J mice was investigated by assessing behavioral performance in middle adolescence. We demonstrated that, mice in MS group displayed decreased anxiety-like behavior and increased exploratory behavior than controls in the open field test and elevated plus maze test. Furthermore, MS mice exhibited improved hippocampal-dependent spatial learning in the Morris water maze test. This performance indicated behavioral resilience to early life stress. The protein expression levels of Homer1 isoforms, which are implicated in a variety of neuropsychiatric disorders, were evaluated using Western blot analysis. A significant increase in hippocampal Homer1a protein expression was observed immediately after MS, which subsequently decreased until adolescence (PND 27-42), when a significant increase was observed again. This distinctive change of hippocampal Homer1a protein expression pattern indicated that hippocampal Homer1a might play a role in behavioral resilience to MS in female C57BL/6J mice. In conclusion, this study demonstrated that exposure to a single 24 h MS at PND 9 promoted behavioral resilience of female C57BL/6J mice in middle adolescence. This behavioral resilience might be related to increased expression of hippocampal Homer1a.

Two-stage adversarial learning based unsupervised domain adaptation for retinal OCT segmentation.

BACKGROUND: Deep learning based optical coherence tomography (OCT) segmentation methods have achieved excellent results, allowing quantitative analysis of large-scale data. However, OCT images are often acquired by different devices or under different imaging protocols, which leads to serious domain shift problem. This in turn results in performance degradation of segmentation models. PURPOSE: Aiming at the domain shift problem, we propose a two-stage adversarial learning based network (TSANet) that accomplishes unsupervised cross-domain OCT segmentation. METHODS: In the first stage, a Fourier transform based approach is adopted to reduce image style differences from the image level. Then, adversarial learning networks, including a segmenter and a discriminator, are designed to achieve inter-domain consistency in the segmentation output. In the second stage, pseudo labels of selected unlabeled target domain training data are used to fine-tune the segmenter, which further improves its generalization capability. The proposed method was tested on cross-domain datasets for choroid or retinoschisis segmentation tasks. For choroid segmentation, the model was trained on 400 images and validated on 100 images from the source domain, and then trained on 1320 unlabeled images and tested on 330 images from target domain I, and also trained on 400 unlabeled images and tested on 200 images from target domain II. For retinoschisis segmentation, the model was trained on 1284 images and validated on 312 images from the source domain, and then trained on 1024 unlabeled images and tested on 200 images from the target domain. RESULTS: The proposed method achieved significantly improved results over that without domain adaptation, with improvement of 8.34%, 55.82% and 3.53% in intersection over union (IoU) respectively for the three test sets. The performance is better than some state-of-the-art domain adaptation methods. CONCLUSIONS: The proposed TSANet, with image level adaptation, feature level adaptation and pseudo-label based fine-tuning, achieved excellent cross-domain generalization. This alleviates the burden of obtaining additional manual labels when adapting the deep learning model to new OCT data.

Changing the spin disorder of two-dimensional magnetic Cr2TiC2Tx to long-range order through noble metal adhesion.

To enhance the use of Cr2TiC2Tx MXene in spin electronics, it is essential to transform its spin-disordered state into a long-range ordered spin state. In this study, first-principles calculations show that Rh layers adhered to the Cr2TiC2Tx surfaces can transform its spin disordered state into a long-range spin order by donating electrons to the O terminations, resulting in Cr2TiC2Tx becoming a single-layer A-type antiferromagnet. As the proportion of F termination increases from 0 to 100%, the exchange coupling constant J1 of the compound escalates from 0.5 to 15.9 meV. Concurrently, the Néel temperature experiences a significant rise from 8 K to 110 K. The analysis of the density of states reveals that the obtained Cr2TiC2Tx exhibits excellent conductivity with O termination and semiconductor characteristics with F termination. These unique features make Cr2TiC2Tx a promising magnetic material for application in spin electronics.

Simulated microgravity increases CD226+ Lin- CD117- Sca1+ mesenchymal stem cells in mice.

Microgravity is one of the most common causes counting for the bone loss. Mesenchymal stem cells (MSCs) contribute greatly to the differentiation and function of bone related cells. The development of novel MSCs biomarkers is critical for implementing effective therapies for microgravity induced bone loss. We aimed to find the new molecules involved in the differentiation and function of MSCs in mouse simulated microgravity model. We found CD226 was preferentially expressed on a subset of MSCs. Simulation of microgravity treatment significantly increased the proportion of CD226+ Lin- CD117- Sca1+ MSCs. The CD226+ MSCs produced higher IL-6, M-CSF, RANKL and lower CD200 expression, and promoted osteoclast differentiation. This study provides pivotal information to understand the role of CD226 in MSCs, and inspires new ideas for prevention of bone loss related diseases.

Automatic zoning for retinopathy of prematurity with a key area location system.

Retinopathy of prematurity (ROP) usually occurs in premature or low birth weight infants and has been an important cause of childhood blindness worldwide. Diagnosis and treatment of ROP are mainly based on stage, zone and disease, where the zone is more important than the stage for serious ROP. However, due to the great subjectivity and difference of ophthalmologists in the diagnosis of ROP zoning, it is challenging to achieve accurate and objective ROP zoning diagnosis. To address it, we propose a new key area location (KAL) system to achieve automatic and objective ROP zoning based on its definition, which consists of a key point location network and an object detection network. Firstly, to achieve the balance between real-time and high-accuracy, a lightweight residual heatmap network (LRH-Net) is designed to achieve the location of the optic disc (OD) and macular center, which transforms the location problem into a pixel-level regression problem based on the heatmap regression method and maximum likelihood estimation theory. In addition, to meet the needs of clinical accuracy and real-time detection, we use the one-stage object detection framework Yolov3 to achieve ROP lesion location. Finally, the experimental results have demonstrated that the proposed KAL system has achieved better performance on key point location (6.13 and 17.03 pixels error for OD and macular center location) and ROP lesion location (93.05% for AP50), and the ROP zoning results based on it have good consistency with the results manually labeled by clinicians, which can support clinical decision-making and help ophthalmologists correctly interpret ROP zoning, reducing subjective differences of diagnosis and increasing the interpretability of zoning results.

DRFNet: a deep radiomic fusion network for nAMD/PCV differentiation in OCT images.

Objective.Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) present many similar clinical features. However, there are significant differences in the progression of nAMD and PCV. and it is crucial to make accurate diagnosis for treatment. In this paper, we propose a structure-radiomic fusion network (DRFNet) to differentiate PCV and nAMD in optical coherence tomography (OCT) images.Approach.The subnetwork (RIMNet) is designed to automatically segment the lesion of nAMD and PCV. Another subnetwork (StrEncoder) is designed to extract deep structural features of the segmented lesion. The subnetwork (RadEncoder) is designed to extract radiomic features from the segmented lesions based on radiomics. 305 eyes (155 with nAMD and 150 with PCV) are included and manually annotated CNV region in this study. The proposed method was trained and evaluated by 4-fold cross validation using the collected data and was compared with the advanced differentiation methods.Main results.The proposed method achieved high classification performace of nAMD/PCV differentiation in OCT images, which was an improvement of 4.68 compared with other best method.Significance. The presented structure-radiomic fusion network (DRFNet) has great performance of diagnosing nAMD and PCV and high clinical value by using OCT instead of indocyanine green angiography.

Effects of glutaraldehyde and povidone-iodine on apoptosis of grass carp liver and hepatocytes.

Since disinfectants are used all over the world to treat illnesses in people and other animals, they pose a major risk to human health. The comprehensive effects of disinfectant treatments on fish liver, especially the impacts on oxidative stress, toxicological effects, transcriptome profiles, and apoptosis, have not yet been fully analyzed. In the current investigation, healthy grass carp were exposed to 80 µg/L glutaraldehyde or 50 µg/L povidone-iodine for 30 days. First, the findings of enzyme activity tests demonstrated that the administration of glutaraldehyde could considerably increase oxidative stress by lowering T-SOD, CAT, and GPx and raising MDA. Furthermore, KEGG research revealed that exposure to glutaraldehyde and povidone-iodine stimulated the PPAR signal pathway. To further elucidate the transcriptome results, the relative expressions of related DEGs in the PPAR signal pathway were verified. Glutaraldehyde induced apoptosis in liver tissue of grass carp; however, it activated cytotoxicity and apoptosis in grass carp hepatocytes when exposed to glutaraldehyde or povidone-iodine. According to the current study, disinfectants can cause the impairment of the immune system, oxidative stress, and attenuation of the PPAR signal pathway in the liver of grass carp, making them detrimental as dietary supplements for grass carp, particularly in the aquaculture sector.

Single-Cell Transcriptomics Reveals the Ameliorative Effect of Oridonin on Septic Liver Injury.

Sepsis is a life-threatening syndrome leading to hemodynamic instability and potential organ dysfunction. Oridonin, commonly used in Traditional Chinese Medicine (TCM), exhibits significant anti-inflammation activity. To explore the protective mechanisms of oridonin against the pathophysiological changes, the authors conducted single-cell transcriptome (scRNA-seq) analysis on septic liver models induced by cecal ligation and puncture (CLP). They obtained a total of 63,486 cells, distributed across 11 major cell clusters, and concentrated their analysis on four specific clusters (hepatocytes/Heps, macrophages, endothelial/Endos and T/NK) based on their changes in proportion during sepsis and under oridonin treatment. Firstly, biological changes in Hep, which are related to metabolic dysregulation and pro-inflammatory signaling, are observed during sepsis. Secondly, they uncovered the dynamic profiles of macrophage's phenotype, indicating that a substantial number of macrophages exhibited a M1-skewed phenotype associated with pro-inflammatory characteristics in septic model. Thirdly, they detected an upregulation of both inflammatory cytokines and transcriptomic factor Nfkb1 expression within Endo, along with slight capillarization during sepsis. Moreover, excessive accumulation of cytotoxic NK led to an immune imbalance. Though, oridonin ameliorated inflammatory-related responses and improved the liver dysfunction in septic mice. This study provides fundamental evidence of the protective effects of oridonin against sepsis-induced cytokine storm.

Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Defining the biogeographical map and potential bacterial translocation of microbiome in human 'surface organs'.

The microbiome in a specific human organ has been well-studied, but few reports have investigated the multi-organ microbiome as a whole. Here, we aim to analyse the intra-individual inter-organ and intra-organ microbiome in deceased humans. We collected 1608 samples from 53 sites of 7 surface organs (oral cavity, esophagus, stomach, small intestine, appendix, large intestine and skin; n = 33 subjects) and performed microbiome profiling, including 16S full-length sequencing. Microbial diversity varied dramatically among organs, and core microbial species co-existed in different intra-individual organs. We deciphered microbial changes across distinct intra-organ sites, and identified signature microbes, their functional traits, and interactions specific to each site. We revealed significant microbial heterogeneity between paired mucosa-lumen samples of stomach, small intestine, and large intestine. Finally, we established the landscape of inter-organ relationships of microbes along the digestive tract. Therefore, we generate a catalogue of bacterial composition, diversity, interaction, functional traits, and bacterial translocation in human at inter-organ and intra-organ levels.

Maternal exposure to dibutyl phthalate (DBP) impairs angiogenesis and AR signalling pathway through suppression of TGFB1I1 in hypospadias offspring.

Early exposure to dibutyl phthalate (DBP) can cause hypospadias in newborn foetuses. However, the underlying molecular mechanism is not well defined. Aberrant angiogenesis is associated with various dysplasias including urogenital deficits. In vivo and in vitro angiogenesis assays showed reduced angiogenesis in the hypospadias group and DBP exposed group. RNA-sequencing analysis of DBP-treated HUVECs revealed decreased expression of transforming growth factor beta 1-induced transcript 1 (TGFB1I1) and a significantly enriched angiogenesis-associated pathway. Further experiments revealed that decreased TGFB1I1 expression was associated with disrupted tube formation and migration, which resulted in decreased angiogenesis. Functional assays revealed that the overexpression of TGFB1I1 promoted tube formation and migration of HUVECs in the DBP-treated group. Moreover, we showed that the transcription factor AR was regulated by TGFB1I1 through inhibiting its translocation from the cytoplasm to the nucleus. Together, our results identified TGFB1I1 as a component of aberrant angiogenesis in hypospadias rats and its interaction with AR might be a potential target for hypospadias development.

20(S)-Ginsenoside Rg2 amino acid derivatives for anti hemorrhagic shock: Synthesis, characterization and evaluation.

The purpose of this study is to screen a novel Rg2 derivative for anti hemorrhagic shock. Eight Rg2 amino acid ester derivatives were designed and synthesized, and their effects on hypoxia and shock were studied. Among them, the derivative 1 (D1) exhibited excellent anti hypoxia by promoting survival rate of H9c2 cells damaged by hypoxia. D1 improved physiological indicators of the rats in hemorrhagic shock, such as blood pressure, heart rate, lactate, acid-base balance, and alleviate oxidative stress and inflammatory damage. Its latent mechanisms were explored by a method of plasma metabolomics based on UPLC-QTOF-MS. As a result, a total of 16 biomarkers were identified involving 6 metabolic pathways. The results of this study contained that the derivative 1 could be considered as potent drug candidates for anti shock and deserved further research and development.

Aldehyde Dehydrogenase 2 (ALDH2) rs671 Polymorphism is a Predictor of Pulmonary Hypertension Due to Left Heart Disease.

AIM: Pulmonary hypertension due to left heart disease (PH-LHD) is commonly seen in patients with heart failure (HF), but there are limited treatment options. Recent studies have shown an association between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and pulmonary hypertension (PH). Therefore, this study aimed to investigate the occurrence of ALDH2 rs671 polymorphisms, and the association between ALDH2 and risk of PH-LHD in patients with HF. It also investigated different ALDH2 genotypes and examined their association with cardiac structure and function in HF patients with PH-LHD. METHODS: A total of 178 HF patients were consecutively enrolled in this study: 102 without PH-LHD and 76 with PH-LHD. Clinical data, parameters of echocardiography, and relevant biochemical indexes were recorded in both groups. Differences in data obtained between groups were compared, and the risk of variant ALDH2 polymorphisms with PH-LHD in HF patients was analysed using univariate and multivariate logistic regression. RESULTS: The prevalence of ALDH2 rs671 GA/AA polymorphisms (variant ALDH2) was 24 of 102 patients (23.53%) in the HF without PH-LHD group, and 32 of 76 patients (42.10%) in the HF with PH-LHD group, with a statistically significant difference. Univariate and multivariate logistical regression showed that variant ALDH2 is an independent risk factor for HF combined with PH-LHD. A higher proportion of patients with variant ALDH2 in the HF with PH-LHD group had a tricuspid regurgitation velocity >2.8 m/s, and they had higher values of peak early diastolic velocity of the mitral orifice/peak velocity of the early diastolic wave of the mitral orifice, maximum frequency shift of pulmonary valve flow, and pulmonary artery stiffness. CONCLUSIONS: Variant ALDH2 may be an independent risk factor for HF combined with PH-LHD. Variant ALDH2 may also be involved in pulmonary artery remodelling and is a potential new target for clinical treatment of PH-LHD.

Diastereomers of Steroidal Alkaloids with Cytotoxic Activities against Non-Small-Cell Lung Cancer from the Bulbs of Fritillaria sinica.

Eleven new steroidal alkaloids, along with nine known related compounds, were isolated from the bulbs of Fritillaria sinica. Seven pairs of diastereomers were identified, including six and four 20-deoxy cevanine-type steroidal alkaloid diastereomers with molecular weights of 413 and 415, respectively. Structures were elucidated based on spectroscopic data analysis, chemical derivatization, and single-crystal X-ray diffraction analysis. Compounds 5, 9, 11, 12, 16, and 20 exhibited significant in vitro cytotoxic activity against non-small-cell lung cancer with CC50 values from 6.8 ± 3.9 to 12 ± 5 µM.

Identifying the function of the PI3K-AKT pathway during the pathogenic infection of Macrobrachium rosenbergii.

The phosphoinositide-3-kinase/protein kinase b (PI3K-Akt) pathway is a signalling pathway based on protein phosphorylation and can be activated by a wide range of factors. To investigate the function of the PI3K-AKT signalling pathway in antibacterial immunity, we analysed the gene expression level of three key factors (PI3K, AKT and FoxO) and innate immune factors in immune tissues at different time points after Vibrio parahaemolyticus and Staphylococcus aureus infection. Tissues analysis showed that PI3K, AKT, and FoxO were expressed at high levels in the intestinal, hemocytes and hepatopancreas. Moreover, the expression levels of PI3K, AKT and FoxO can be regulated postinfection by different pathogens. In hemocytes and the intestine, V. parahaemolyticus infection was found to regulate the levels of PI3K, AKT, and FoxO more rapidly; however, an S. aureus infection regulated the levels of these factors more rapidly in the hepatopancreas and gills. Analysis showed that V. parahaemolyticus and S. aureus infection caused changes in the gene expression level of crustin, caspase 3 and NF-κB. Therefore, PI3K-AKT regulates the downstream immune pathway differentially in different immune tissues and participates in the regulation of cell apoptosis and the inflammatory response by activating caspase and NF-κB, respectively, following infection with V. parahaemolyticus and S. aureus.

A Multi-Scale Fusion and Transformer Based Registration Guided Speckle Noise Reduction for OCT Images.

Optical coherence tomography (OCT) images are inevitably affected by speckle noise because OCT is based on low-coherence interference. Multi-frame averaging is one of the effective methods to reduce speckle noise. Before averaging, the misalignment between images must be calibrated. In this paper, in order to reduce misalignment between images caused during the acquisition, a novel multi-scale fusion and Transformer based (MsFTMorph) method is proposed for deformable retinal OCT image registration. The proposed method captures global connectivity and locality with convolutional vision transformer and also incorporates a multi-resolution fusion strategy for learning the global affine transformation. Comparative experiments with other state-of-the-art registration methods demonstrate that the proposed method achieves higher registration accuracy. Guided by the registration, subsequent multi-frame averaging shows better results in speckle noise reduction. The noise is suppressed while the edges can be preserved. In addition, our proposed method has strong cross-domain generalization, which can be directly applied to images acquired by different scanners with different modes.

TOPK promotes the development of psoriasis and worenine alleviates psoriasiform dermatitis by inhibiting TOPK activity.

BACKGROUND: Psoriasis is an inflammatory skin disease. The pathogenesis of psoriasis has not been fully elucidated. T-lymphokine-activated killer cell-originated protein kinase (TOPK) activity increases in a proinflammatory environment, and inhibiting TOPK blocks inflammation. However, whether TOPK is involved in the pathogenesis of psoriasis remains to be identified. OBJECTIVES: We aimed to study the role of TOPK in psoriasis and attempted to find a drug targeting TOPK for the prevention and treatment of psoriasis. METHOD: Firstly, the expressions of TOPK in psoriatic patients, psoriatic cell and animal model were analysed by Gene Expression Omnibus database, immunohistochemistry (IHC) staining and western blot (WB). After inhibiting TOPK by chemical or gene knockout, the effect of TOPK on the development of psoriasis was verified in cell and animal model by WB, qRT-PCR, ELISA, haematoxylin-eosin (H&E) and IHC staining. Moreover, phosphoproteomic analysis was performed to explore the signalling pathways regulated by TOPK in the occurrence and development of psoriasis. Then, an in vitro kinase assay was performed to prove TOPK kinase activity was inhibited by worenine. Ultimately, WB, qRT-PCR, ELISA, H&E and IHC staining were used to verify the anti-psoriasis effect of worenine by inhibiting TOPK was in cell and animal model. RESULTS: In this study, we found that TOPK was highly expressed in psoriasis patients, psoriatic cell and animal model, which suggests that TOPK might be associated with psoriasis pathogenesis. Interestingly, chemical or genetic inhibition of TOPK alleviated M5- and imiquimod (IMQ)-induced psoriasis-like dermatitis, which further confirmed the role of TOPK in promoting the development of psoriasis. Moreover, we determined that worenine inhibited TOPK kinase activity. In addition, worenine relieved M5- and IMQ-induced psoriasiform dermatitis by inhibiting TOPK activity. CONCLUSIONS: T-lymphokine-activated killer cell-originated protein kinase promotes the development of psoriasis. Therefore, TOPK might be a promising drug target for the prevention and treatment of psoriasis. Worenine alleviates psoriasiform dermatitis by inhibiting TOPK activity, providing new strategies for clinical intervention.