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Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of butorphanol on ALI and investigated its underlying mechanisms. We established a “two-hit” rat model and “two-hit” cell model to prove our hypothesis. Rats were divided into four groups [control, “two-hit” (OA + LPS), “two-hit” + butorphanol (4 mg/kg and 8 mg/kg) (OA + LPS + B1 and OA + LPS + B2)]. RPMVE cells were divided into four groups [control, “two-hit” (OA + LPS), “two-hit” + butorphanol (4 μM and 8 μM) (OA + LPS + 4 μM and OA + LPS + 8 μM)]. Inflammatory injury was assessed by the histopathology and W/D ratio, inflammatory cytokines, and arterial blood gas analysis. Apoptosis was assessed by Western blotting and flow cytometry. The effect of NF-κB p65 was detected by ELISA. Butorphanol could relieve the “two-hit” induced lung injury, the expression of TNF, IL-1β, IL-6, and improve lung ventilation. In addition, butorphanol decreased Bax and cleaved caspase-3, increased an antiapoptotic protein (Bcl-2), and inhibited the “two-hit” cell apoptosis ratio. Moreover, butorphanol suppressed NF-κB p65 activity in rat lung injury. Our research showed that butorphanol may attenuate “two-hit”-induced lung injury by regulating the activity of NF-κB p65, which may supply more evidence for ALI treatment.

In this study, we have, for the first time, demonstrated the beneficial effects of transcranial magneto-acoustic stimulation (TMAS), a technique based on focused ultrasound stimulation within static magnetic field, on the learning and memory abilities and neuroplasticity of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Our results showed that chronic TMAS treatment (2 weeks) improved the outcome of Morris water maze, long-term potentiation (LTP), and dendritic spine densities in the dentate gyrus (DG) region of the hippocampus of PD model mice. To further investigate into the underlying mechanisms of these beneficial effects by TMAS, we quantified the proteins in the hippocampus that regulated neuroplasticity. Results showed that the level of postsynaptic density protein 95 was elevated in the brain of TMAS-treated PD model mice while the level of synaptophysin (SYP) did not show any change. We further quantified proteins that mediated neuroplasticity mechanisms, such as brain-derived neurotrophic factor (BDNF) and other important proteins that mediated neuroplasticity. Results showed that TMAS treatment elevated the levels of BDNF, cAMP response element–binding protein (CREB), and protein kinase B (p-Akt) in the PD model mouse hippocampus, but not in the non-PD mouse hippocampus. These results suggest that the beneficial effects on the neuroplasticity of PD model mice treated with TMAS could possibly be conducted through postsynaptic regulations and mediated by BDNF.

Background Thyroid carcinoma is the most common malignant endocrine tumour, and its prevalence has been on the rise in recent years. However, mechanisms underlying the metastasis of thyroid carcinoma and candidate biomarkers remain elusive. In this study, we screened genes involved in the virulence and metastasis of papillary thyroid carcinoma (PTC). Methods Oxford Nanopore Technology full-length transcriptome sequencing and bioinformatic analyses were performed to analyse differentially expressed genes (DEGs) in PTC. We collected 15 cancerous and paracancerous tissue pairs from patients with PTC for RNA sequencing. The significance thresholds for DEGs were |log2(fold change)| ≥ 1 and false discovery rate (FDR) < 0.01. Gene Ontology and Kyoto Encyclopaedia Gene and Genome pathway enrichment analyses of the 50 most significant DEGs were performed. Immunohistochemistry was used to evaluate LAMB3 expression in tissue microarrays (58 pairs of PTC samples) and its correlation with clinicopathological parameters. Differences in gene expression between cancerous and paracancerous tissues were analysed using the Wilcoxon test. The correlation between gene expression and clinical variables was assessed using Fisher’s exact test. Results Transcriptomic analysis revealed the presence of 1,687 DEGs in PTC, and the expression of 804 and 883 genes was found to be upregulated and downregulated, respectively. LAMB3 expression was significantly elevated in cancerous tissues when compared to that in paracancerous tissues ( p  < 0.001). LAMB3 expression was significantly positively associated with PTC tumour tissue size ( p  = 0.001, r  = 0.49) and T stage ( p  = 0.017, r  = 0.339). Conclusions Our findings suggest that LAMB3 expression significantly increases in PTC and it is associated with tumor size and T stage.

The Internet of Things (IoT) leads the era of interconnection, where numerous sensors and devices are being introduced and interconnected. To support such an amount of data traffic, wireless communication technologies have to overcome available spectrum shortage and complex fading channels. The transform domain communication system (TDCS) is a cognitive anti-interference communication system with a low probability of detection and dynamic spectrum sensing and accessing. However, the non-continuous and asymmetric spectrum brings new challenges to the traditional TDCS block-type pilot, which uses a series of discrete symbols in the time domain as pilots. Low efficiency and poor adaptability in fast-varying channels are the main drawbacks for the block-type pilot in TDCS. In this study, a frequency domain non-uniform pilot design method was proposed with intersecting, skewing, and edging of three typical non-uniform pilots. Some numerical examples are also presented with multipath model COST207RAx4 to verify the proposed methods in the bit error ratio and the mean square error. Compared with traditional block-type pilot, the proposed method can adapt to the fast-varying channels, as well as the non-continuous and asymmetric spectrum conditions with much higher efficiency.

Nonalcoholic steatohepatitis (NASH) is a prevalent chronic disease, yet its exact mechanisms and effective treatments remain elusive. Nuclear receptor subfamily 5 group A member 2 (NR5A2), a transcription factor closely associated with cholesterol metabolism in the liver, has been hindered from comprehensive investigation due to the lethality of NR5A2 loss in cell lines and animal models. To elucidate the role of NR5A2 in NASH, we generated hepatocyte-specific knockout mice for Nr5a2 (Nr5a2 HKO ) and examined their liver morphology across different age groups under a regular diet. Furthermore, we established cell lines expressing haploid levels of NR5A2 and subsequently reintroduced various isoforms of NR5A2. In the liver of Nr5a2 HKO mice, inflammation and fibrosis spontaneously emerged from an early age, independent of lipid accumulation. Pyroptosis occurred in NR5A2-deficient cell lines, and different isoforms of NR5A2 reversed this form of cell death. Our findings unveiled that inhibition of NR5A2 triggers pyroptosis, a proinflammatory mode of cell death primarily mediated by the activation of the NF-κB pathway induced by reactive oxygen species (ROS). As a transcriptionally regulated molecule of NR5A2, aldehyde dehydrogenase 1 family member B1 (ALDH1B1) participates in pyroptosis through modulation of ROS level. In conclusion, the diverse isoforms of NR5A2 exert hepatoprotective effects against NASH by maintaining a finely tuned balance of ROS, which is contingent upon the activity of ALDH1B1. Highlights NR5A2 hepatocyte knockout mice aggravate NASH through NF-κB pathway and pyroptosis. NR5A2 transcriptionally upregulates ALDH1B1, inhibiting ROS. ALDH1B1 rescue experiments underscored its significance in NR5A2 mediated pyroptosis. Distinct NR5A2 isoforms exert consistent effect on ALDH1B1 expression and pyroptosis.

Background The SARS-CoV-2 RNA was detected positive again after discharged from hospital in some COVID-19 patients, with or without clinical symptoms such as fever or dry cough. Methods 1008 severe COVID-19 patients, with SARS-CoV-2 RNA positive detected with the mixed specimen of nasopharyngeal swab and oropharyngeal swab by real-time fluorescence quantitative PCR (RT-qPCR), were selected to monitor SARS-CoV-2 RNA with the 12 types of specimens by RT-qPCR during hospitalization. All of 20 discharged cases with COVID-19 were selected to detect SARS-CoV-2 RNA in isolation period with 7 types of specimens by RT-qPCR before releasing the isolation period. Results Of the enrolled 1008 severe patients, the nasopharyngeal swab specimens showed the highest positive rate of SARS-CoV-2 RNA (71.06%), followed by alveolar lavage fluid (66.67%), oropharyngeal swab (30.77%), sputum (28.53%), urine (16.30%), blood (12.5%), stool (12.21%), anal swab (11.22%) and corneal secretion (2.99%), and SARS-CoV-2 RNA couldn’t be detected in other types of specimen in this study. Of the 20 discharged cases during the isolation period, the positive rate of SARS-CoV-2 RNA was 30% (6/20): 2 cases were positive in sputum at the eighth and ninth day after discharge, respectively, 1 case was positive in nasopharynx swab at the sixth day after discharge, 1 case was positive in anal swab at the eighth day after discharge, and 1 case was positive in 3 specimens (nasopharynx swab, oropharynx swab and sputum) simultaneously at the fourth day after discharge, and no positive SARS-CoV-2 RNA was detected in other specimens including stool, urine and blood at the discharged patients. Conclusions SARS-CoV-2 RNA should be detected in multiple specimens, such as nasopharynx swab, oropharynx swab, sputum, and if necessary, stool and anal swab specimens should be performed simultaneously at discharge when the patients were considered for clinical cure and before releasing the isolation period.

The relationship between antimitochondrial antibody (AMA) levels and the severity or prognosis of primary biliary cholangitis (PBC) is unclear. This study explored the clinical significance of serum IgG antimitochondrial M2 antibody (IgG-M2) levels. From 2008 to 2017, a retrospective analysis was conducted with PBC patients who had available quantitative values of serum IgG-M2 levels obtained with ELISA based on triple expression hybrid clones. The patients were divided into two groups based on high and low concentrations of IgG-M2. Baseline parameters, the incidence of adverse events, and prognosis were compared. Among the 530 PBC patients, the levels of albumin, cholinesterase, hemoglobin, fibrinogen and triglycerides and the red blood cell count were significantly lower in the high-concentration group than in the low-concentration group (n = 263, 49.6%). The red cell distribution width (RDW) and levels of serum immunoglobulin (Ig) G, IgM and IgA were significantly higher in the high-concentration group than in the low-concentration group. Spearman's correlation analysis suggested that the correlation between the above baseline indicators and IgG-M2 levels was statistically significant but weak (r < 0.2, P < 0.05). In total, 203 patients were followed up, of whom 87 (42.9%) were in the high-concentration group. During the median follow-up period of 52 months (range: 28-75), 121 (59.6%) experienced hepatic decompensation, and 37 (18.2%) died or underwent liver transplantation. There was no significant difference in the incidence of complications or survival (log-rank test: P = 0.079) between the two groups. One year after ursodeoxycholic acid (UDCA) treatment, the two groups had similar responses. In addition, the levels of IgG-M2 did not fluctuate significantly during treatment. IgG-M2 levels were not related to the disease severity, prognosis or efficacy of UDCA. The levels of IgG-M2 did not change significantly during treatment.

Nonalcoholic fatty liver disease (NAFLD) is due to the excessive lipid accumulation within hepatocytes. Metabolic nuclear receptors (MNRs) play great roles in lipid homeostasis. We have identified a novel long noncoding RNA (lncRNA), lnc-HC, which regulates hepatocytic cholesterol metabolism through reducing Cyp7a1 and Abca1 expression. Here, we further elucidate its roles in hepatic fatty acid and triglyceride (TG) metabolism through a novel lncRNA regulatory mechanism. The most prominent target of lnc-HC identified by in vitro study is PPARγ. Further studies revealed that lnc-HC negatively regulates PPARγ at both the mRNA and protein levels and suppresses hepatocytic lipid droplet formation. Importantly, the function of lnc-HC in regulating PPARγ expression depends on modulating miR-130b-3p expression from the transcriptional to the post-transcriptional level, not through lncRNA’s critical modulating patterns. In vivo, the reduction of lnc-HC expression significantly decreases miR-130b-3p expression, induces PPARγ expression, and increases TG concentration in rat livers with hyperlipidemia. These findings further help in understanding the regulatory pattern of lnc-HC in hepatic lipid metabolism and might present a possible therapeutic target for improving lipid homeostasis. [Display omitted]

Aims and objectives To construct a risk assessment scale for medical adhesive‐related skin injuries (MARSI) at the peripherally inserted central catheter (PICC) insertion site in oncology patients and test its reliability and validity. Design The STARD 2015 statement guided this study. Methods Literature research and a modified Delphi method were adopted in this study. A total of 31 experts participated in two rounds of consultation to build the assessment scale. A convenient sampling method was used to select 195 oncology patients at the PICC clinic from January to June 2022. Inter‐rater reliability was used to test the reliability of the scale. Validity was evaluated using the content validity index (CVI) and predictive validity. Results After the two rounds of consultation, the assessment scale with five dimensions and 13 primary entries and 36 secondary entries was developed, and the expert authority coefficients for both were 0.90. The inter‐rater reliability was 0.968. The CVIs of the items ranged from 0.83 to 1.00. The area under the subject's work characteristic curve was 0.757, and the sensitivity and specificity of the scale were 80.0% and 65.6%, respectively, at a cutoff score of 15.5.

Objective Thyroid capsule invasion (TCI) predicts early progression in papillary thyroid microcarcinoma (PTMC). This study aimed to develop an integrated model that combines handcrafted peri-tumoral radiomics features with deep learning (DL)-derived intra-tumoral features for accurate early prediction of TCI, to support clinical decision-making. Materials and methods Retrospective data from 964 patients with 964 pathologically confirmed PTMC lesions across three centers were collected. Radiomics features were extracted from multiple peri-tumoral regions, and the optimal peri-tumor region with the best radiomics features was selected using a support vector machine (SVM). The selected radiomics features were then combined with intra-tumoral DL features extracted from the tumors before being fed into four different DL models for training and validation. Performance was validated on the internal ( n  = 177) and external ( n  = 84) test sets. Six radiologists (senior/attending/junior) assessed TCI with/without DL assistance. Results The radiomics features, which achieved the best diagnostic performance with an AUC of 0.795 using SVM, were extracted from the peri-tumor region with 30% expansion from the original tumor. By further combining these radiomics features with intra-tumoral DL features, four different DL models were established to identify TCI in PTMC. Swin-Transformer achieved superior performance (internal AUC: 0.923; external AUC: 0.892). With DL model assistance, the AUCs of six radiologists significantly improved, for example, from 0.720 to 0.796 and from 0.725 to 0.790 for senior radiologists, and similar gains were observed for attending and junior radiologists. Conclusions As an effective clinical assistive tool,  this integrated model can provide TCI identification with high level of accuracy. With its ability to enhance radiologists’ diagnostic performance, it supports early PTMC risk stratification and personalized intervention. Critical relevance statement This retrospective multicenter study establishes an integrated model for identifying TCI in PTMC. The model significantly enhances radiologists’ diagnostic precision across multiple experience levels, supporting early clinical decision-making for optimized intervention strategies. Key Points Accurate prediction of TCI facilitates early assessment of PTMC progression and guides subsequent individualized clinical management. DL significantly improves the predictive performance for TCI. DL effectively assists radiologists in TCI diagnosis. Graphical Abstract