Efficacy and Safety of Insulin Degludec/Insulin Aspart versus Biphasic Insulin Aspart 30 in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Background: We systematically reviewed and analyzed the efficacy and safety of insulin degludec/insulin as-part (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes (T2D). Methods: We used computers to search the Embase, PubMed, Clinical Trials, and the Cochrane Library database, and collected randomized controlled trials (RCTs) on the treatment of IDegAsp versus BIAsp 30 in T2D patients. The research period was from the establishment of the database to May 19, 2023. We used Review Manager 5.20 statistical software for systematic meta-analysis. Results: We included 8 RCTs with 2281 participants. IDegAsp was better to BIAsp30 in improving fasting plasma glucose (FPG) levels (P<0.001) and reducing the endpoint daily average insulin dose (P<0.01). Furthermore, compared with BIAsp30, IDegAsp significantly reduced the risk of nocturnal hypoglycemic events (P<0.001). However, there was no significant difference in the improvement of body weight change (P=0.99), glycosylated hemoglobin (P=0.50), the overall risk of hypoglycemic events (P=0.57) and adverse events (P=0.89) between the two groups. Conclusion: Compared with BIAsp30, IDegAsp could significantly reduce FPG levels, insulin dosage, and the risk of nocturnal hypoglycemic events in T2D patients, without increasing the overall risk of adverse events.

Eruptive xanthomas in a patient with severe hypertriglyceridemia: A case report.

BACKGROUND: Xanthomatosis, a metabolic disorder causing yellow growths (xanthomas), poses challenges in lipid metabolism. This case study introduces the first documented instance within China's Yi population, emphasizing the need to explore dietary habits and treatment strategies tailored to this specific community. CASE SUMMARY: Xanthomatosis is a metabolic disorder where lipid metabolism goes awry, resulting in the development of yellowish growths called xanthomas. A male patient, 47 years of age, from China's Yi population, who is obese, visited our dermatology clinic complaining of widespread, non-painful rashes that have been present for two weeks. The patient works as a chef and has a diet that frequently includes oily and greasy foods. This case represents the initial documentation of xanthomatosis within the Yi population in China, offering a theoretical foundation for understanding dietary patterns and treatment options specific to the Yi community. CONCLUSION: The first report of xanthomatosis in the Yi population in China lays a theoretical foundation for understanding Yi dietary patterns and treatment.

The diagnosis and management of multiple ground-glass nodules in the lung.

The prevalence of low-dose CT (LDCT) in lung cancer screening has gradually increased, and more and more lung ground glass nodules (GGNs) have been detected. So far, a consensus has been reached on the treatment of single pulmonary ground glass nodules, and there have been many guidelines that can be widely accepted. However, at present, more than half of the patients have more than one nodule when pulmonary ground glass nodules are found, which means that different treatment methods for nodules may have different effects on the prognosis or quality of life of patients. This article reviews the research progress in the diagnosis and treatment strategies of pulmonary multiple lesions manifested as GGNs.

Pleural carbohydrate antigen 50 and malignant pleural effusion: a prospective, double-blind diagnostic accuracy test.

Background: Serum carbohydrate antigen 50 (CA50) is an auxiliary diagnostic marker for various solid tumors, but it remains unclear whether CA50 in pleural fluid can assist in the diagnosis of malignant pleural effusion (MPE). This study aimed to evaluate the diagnostic accuracy of pleural fluid CA50 for MPE in pleural effusion patients with undetermined causes. Methods: This study prospectively recruited pleural effusion patients with undetermined causes who visited the Affiliated Hospital of Inner Mongolia Medical University between September 2018 and July 2021. We measured pleural fluid CA50 level with an electrochemiluminescence assay. We analyzed the diagnostic accuracy of CA50 and carcinoembryonic antigen (CEA) for MPE with the receiver operating characteristic (ROC) curve. The net benefits of CA50 and CEA were analyzed using the decision curve analysis (DCA). Results: We enrolled 66 MPEs and 87 benign pleural effusions (BPEs). MPE patients had significantly higher CA50 and CEA than BPE patients. The area under the ROC curve (AUC) of CA50 was 0.72 (95% CI: 0.63-0.80). CA50 had a sensitivity of 0.30 (95% CI: 0.19-0.41) and a specificity of 1.00 (95% CI: 1.00-1.00) at the threshold of 15 IU/mL. The decision curve of CA50 was above the reference line at the calculated risk probability of between 0.30 and 1.00. Venn diagram indicated that some patients with low CEA (<50 or <150 ng/mL) and/or negative cytology can be identified by positive CA50 (>15 IU/mL). Conclusions: Pleural fluid CA50 has moderate accuracy and net benefit for detecting MPE. CA50 >15 IU/mL can be used to diagnose MPE. The combination of CA50 and CEA improves the diagnostic sensitivity for MPE.

Rosmanol Triggers Apoptosis Against MNNG-induced Gastric Carcinogenesis in Rats through Attenuation of the P13K/AKT/HMBG1 Signaling Pathway.

BACKGROUND: Gastric cancer (GC) is a frequent malignant neoplasm found in China. Despite numerous therapeutic methodologies to ameliorate the well-being of GC patients, their efficiency remains inadequate. OBJECTIVE: Rosmanol (RML) is a phenolic diterpene compound with antioxidant and anticancer activities. In the current research, the apoptotic efficacy of RML on methylnitronitrosoguanidine (MNNG)-induced GC model was determined. MATERIALS AND METHODS: The rats were allocated into four sets, viz., normal control, MNNG (200 mg/kg bw) + NaCl, MNNG + RML (20 mg/kg), and RML (20 mg/kg) orally treated for 20 weeks. RESULTS: The results exposed that GC rats revealed higher (P<0.05) levels of TBARS and reduced antioxidant status in the stomach and liver tissues counter to other groups. In contrast, the TBARS level was substantially alleviated (P<0.05) and restored the antioxidant status in RMLadministered rats. Histopathologic assessment of gastric tissue unveiled that an MNNG-induced group presented squamous cell carcinoma with keratin pearls. The administration of RML reduced GC incidence, and only mild dysplasia was observed. Further, RML alleviated Bcl-2, P13K, AKT, and HMGB1, as evidenced by RT-PCR and Western blot analysis. CONCLUSION: Furthermore, RML triggered caspase-mediated mitochondrial apoptosis through the inactivation of the PI3K/AKT/HMGB1 pathway, eventually leading to GC cell death. This highlights that RML may be a potential natural antioxidant employed as a chemoprotective agent in GC rats.

Plexin D1 negatively regulates macrophage-derived foam cell migration via the focal adhesion kinase/Paxillin pathway.

BACKGROUND: Macrophage-derived foam cell formation is a hallmark of atherosclerosis and is retained during plaque formation. Strategies to inhibit the accumulation of these cells hold promise as viable options for treating atherosclerosis. Plexin D1 (PLXND1), a member of the Plexin family, has elevated expression in atherosclerotic plaques and correlates with cell migration; however, its role in macrophages remains unclear. We hypothesize that the guidance receptor PLXND1 negatively regulating macrophage mobility to promote the progression of atherosclerosis. METHODS: We utilized a mouse model of atherosclerosis based on a high-fat diet and an ox-LDL- induced foam cell model to assess PLXND1 levels and their impact on cell migration. Through western blotting, Transwell assays, and immunofluorescence staining, we explored the potential mechanism by which PLXND1 mediates foam cell motility in atherosclerosis. RESULTS: Our study identifies a critical role for PLXND1 in atherosclerosis plaques and in a low-migration capacity foam cell model induced by ox-LDL. In the aortic sinus plaques of ApoE-/- mice, immunofluorescence staining revealed significant upregulation of PLXND1 and Sema3E, with colocalization in macrophages. In macrophages treated with ox-LDL, increased expression of PLXND1 led to reduced pseudopodia formation and decreased migratory capacity. PLXND1 is involved in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK. Additionally, FAK inhibitors counteract the ox-LDL-induced migration suppression by modulating the phosphorylation states of FAK, Paxillin and their downstream effectors CDC42 and PAK. CONCLUSION: Our findings indicate that PLXND1 plays a role in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK to promoting atherosclerosis.

Global climate change: Effects of future temperatures on emergency department visits for mental disorders in Beijing, China.

Rising temperatures can increase the risk of mental disorders. As climate change intensifies, the future disease burden due to mental disorders may be underestimated. Using data on the number of daily emergency department visits for mental disorders at 30 hospitals in Beijing, China during 2016-2018, the relationship between daily mean temperature and such visits was assessed using a quasi-Poisson model integrated with a distributed lag nonlinear model. Emergency department visits for mental disorders attributed to temperature changes were projected using 26 general circulation models under four climate change scenarios. Stratification analyses were then conducted by disease subtype, sex, and age. The results indicate that the temperature-related health burden from mental disorders was projected to increase consistently throughout the 21st century, mainly driven by high temperatures. The future temperature-related health burden was higher for patients with mental disorders due to the use of psychoactive substances and schizophrenia as well as for women and those aged <65 years. These findings enhance our knowledge of how climate change could affect mental well-being and can be used to advance and refine targeted approaches to mitigating and adapting to climate change with a view on addressing mental disorders.

Coping with alpine habitats: genomic insights into the adaptation strategies of Triplostegia glandulifera (Caprifoliaceae).

How plants find a way to thrive in alpine habitats remains largely unknown. Here we present a chromosome-level genome assembly for an alpine medicinal herb, Triplostegia glandulifera (Caprifoliaceae), and 13 transcriptomes from other species of Dipsacales. We detected a whole-genome duplication event in T. glandulifera that occurred prior to the diversification of Dipsacales. Preferential gene retention after whole-genome duplication was found to contribute to increasing cold-related genes in T. glandulifera. A series of genes putatively associated with alpine adaptation (e.g. CBFs, ERF-VIIs, and RAD51C) exhibited higher expression levels in T. glandulifera than in its low-elevation relative, Lonicera japonica. Comparative genomic analysis among five pairs of high- vs low-elevation species, including a comparison of T. glandulifera and L. japonica, indicated that the gene families related to disease resistance experienced a significantly convergent contraction in alpine plants compared with their lowland relatives. The reduction in gene repertory size was largely concentrated in clades of genes for pathogen recognition (e.g. CNLs, prRLPs, and XII RLKs), while the clades for signal transduction and development remained nearly unchanged. This finding reflects an energy-saving strategy for survival in hostile alpine areas, where there is a tradeoff with less challenge from pathogens and limited resources for growth. We also identified candidate genes for alpine adaptation (e.g. RAD1, DMC1, and MSH3) that were under convergent positive selection or that exhibited a convergent acceleration in evolutionary rate in the investigated alpine plants. Overall, our study provides novel insights into the high-elevation adaptation strategies of this and other alpine plants.

Diagnostic accuracy and cellular origin of pleural fluid CXCR3 ligands for tuberculous pleural effusion.

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.

Antimicrobial Activities of α-Helix and ß-Sheet Peptides against the Major Bovine Respiratory Disease Agent, Mannheimia haemolytica.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one ß-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2 being the most efficacious against multiple isolates. At 8-16 µg/mL, WK2 was bactericidal against Mh 330 in broth, and at 32 µg/mL in the presence of BT cells, it reduced the population by 3 logs CFU/mL without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine) and ONPG (o-Nitrophenyl ß-D-galactopyranoside), with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

Cistanche phenylethanoid glycosides induce apoptosis and pyroptosis in T-cell lymphoma.

Cistanche deserticola, known for its extensive history in Traditional Chinese Medicine (TCM), is valued for its therapeutic properties. Recent studies have identified its anticancer capabilities, yet the mechanisms underlying these properties remain to be fully elucidated. In this study, we determined that a mixture of four cistanche-derived phenylethanoid glycosides (CPhGs), echinacoside, acteoside, 2-acetylacteoside, and cistanoside A, which are among the main bioactive compounds in C. deserticola, eliminated T-cell lymphoma (TCL) cells by inducing apoptosis and pyroptosis in vitro and attenuated tumor growth in vivo in a xenograft mouse model. At the molecular level, these CPhGs elevated P53 by inhibiting the SIRT2-MDM2/P300 and PI3K/AKT carcinogenic axes and activating PTEN-Bax tumor-suppressing signaling. Moreover, CPhGs activated noncanonical and alternative pathways to trigger pyroptosis. Interestingly, CPhGs did not activate canonical NLRP3-caspase-1 pyroptotic signaling pathway; instead, CPhGs suppressed the inflammasome factor NLRP3 and the maturation of IL-1ß. Treatment with a caspase-1/4 inhibitor and silencing of Gasdermin D (GSDMD) or Gasdermin E (GSDME) partially rescued CPhG-induced cell death. Conversely, forced expression of NLRP3 restored cell proliferation. In summary, our results indicate that CPhGs modulate multiple signaling pathways to achieve their anticancer properties and perform dual roles in pyroptosis and NLRP3-driven proliferation. This study offers experimental support for the potential application of CPhGs in the treatment of TCL.

Polygonatum sibiricum (Huang Jing) polysaccharide reduces diabetic cardiomyopathy through increasing cyclic guanosine monophosphate-protein kinase G signaling in diabetic mice.

AIMS/INTRODUCTION: Diabetic cardiomyopathy (DCM) is a prevalent condition among individuals with diabetes, and is associated with a high mortality rate. The anti-oxidant properties of Jing Huang or Polygonatum sibiricum polysaccharide (PSP) have been extensively used to treat diabetes-related disorders; however, its potential effectiveness against DCM remains unknown. This study aimed to investigate PSP's therapeutic effects on DCM in an experimental diabetic mouse model. MATERIALS AND METHODS: To induce insulin resistance, mice were fed a high-fat diet for 3 months, followed by intraperitoneal streptozotocin injection to induce slight hyperglycemia and develop DCM. Both DCM and control mice were given PSP orally for 3 weeks. Western blotting was used to detect the protein expressions of protein kinase G, C/EBP homologous protein, glucose-regulated protein 78, phosphodiesterase type 5, protein kinase R-like endoplasmic reticulum (ER) kinase, and phospho-protein kinase R-like endoplasmic reticulum kinase in heart tissue. RESULTS: The results showed a reduction in bodyweight and blood glucose levels in the PSP therapy group compared with DCM group. PSP also improved cardiac function and had a negligible effect on malondialdehyde activity. Furthermore, the findings showed that PSP alleviated ER and oxidative stress observed in DCM mice hearts, leading to the inhibition of cyclic guanosine monophosphate-specific phosphodiesterase type 5 and cardiac cyclic guanosine monophosphate reactivation. Phosphodiesterase type 5 inhibition reduced high-fat diet-induced cardiac dysfunction and decreased ER stress. CONCLUSIONS: PSP could effectively protect diabetic myocardium by inhibiting endoplasmic reticulum stress. These findings provide crucial insights into the potential of PSP to ameliorate DCM conditions in diabetic mice by decreasing ER and oxidative stress, and enhancing cyclic guanosine monophosphate protein kinase G signaling.

Beta-informativeness-diffusion multilayer graph embedding for brain network analysis.

Brain network analysis provides essential insights into the diagnosis of brain disease. Integrating multiple neuroimaging modalities has been demonstrated to be more effective than using a single modality for brain network analysis. However, a majority of existing brain network analysis methods based on multiple modalities often overlook both complementary information and unique characteristics from various modalities. To tackle this issue, we propose the Beta-Informativeness-Diffusion Multilayer Graph Embedding (BID-MGE) method. The proposed method seamlessly integrates structural connectivity (SC) and functional connectivity (FC) to learn more comprehensive information for diagnosing neuropsychiatric disorders. Specifically, a novel beta distribution mapping function (beta mapping) is utilized to increase vital information and weaken insignificant connections. The refined information helps the diffusion process concentrate on crucial brain regions to capture more discriminative features. To maximize the preservation of the unique characteristics of each modality, we design an optimal scale multilayer brain network, the inter-layer connections of which depend on node informativeness. Then, a multilayer informativeness diffusion is proposed to capture complementary information and unique characteristics from various modalities and generate node representations by incorporating the features of each node with those of their connected nodes. Finally, the node representations are reconfigured using principal component analysis (PCA), and cosine distances are calculated with reference to multiple templates for statistical analysis and classification. We implement the proposed method for brain network analysis of neuropsychiatric disorders. The results indicate that our method effectively identifies crucial brain regions associated with diseases, providing valuable insights into the pathology of the disease, and surpasses other advanced methods in classification performance.

Serum proteomics identify CSF1R as a novel biomarker for postoperative recurrence in chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) presents a high rate of postoperative recurrence, but its recurrent mechanisms are not fully clarified. In this study, we aim to explore biomarkers associated with the recurrence of CRSwNP and shed light on the underlying recurrent mechanisms using serum proteomics. Methods: A prospective cohort of CRSwNP patients was conducted, and serum samples were subjected to proteomic profiling. Participants were followed up for 2 years and divided into non-Recurrence and Recurrence groups and differentially expressed proteins (DEPs) were compared. The top 3 DEPs were validated in the serum and tissue samples in a validation cohort, and their predictive values for recurrence and their associations with macrophages were evaluated. In vitro, circulating macrophages were utilized to explore the influence of candidate proteins on macrophage polarization in underlying recurrent mechanisms of CRSwNP. Results: Sixteen CRSwNP patients completed the follow-up schedule, including 10 patients in the non-Recurrence group and 6 patients in the Recurrence group. Serum proteomics revealed a distinctive protein expression profile between the 2 groups. A validation cohort comprising 51 non-recurrent and 24 recurrent CRSwNP patients was recruited. Enzyme-linked immunosorbent assay (ELISA) results revealed that circulating levels of CSF1R and CDC42 were significantly higher, and DHRS9 levels were lower in the Recurrence group in comparison with the non-Recurrence group. In addition, tissue CSF1R and CDC42 were identified to be enhanced in the Recurrence group compared to the non-Recurrence group. Receiver-operated characteristic (ROC) curves and Kaplan-Meier survival analysis suggest that both serum and tissue CSF1R were associated with the risk of postoperative recurrence. Tissue immunofluorescence (IF) revealed that CSF1R was enhanced in the tissues of patients with recurrence, especially in the mesenchymal region. Multiplex IF highlighted that CSF1R was significantly co-expressed with M2 macrophage markers. In vitro experiments confirmed that CSF1R overexpression promoted macrophage M2 polarization and cytokine production. Conclusion: Serum proteomic signatures may affect postoperative recurrence in CRSwNP patients. CSF1R is a potential biomarker for predicting CRSwNP recurrence. Mechanistically, the recurrence of CRSwNP appears to involve the CSF1R-driven M2 polarization process.

The Interaction Mechanism of Picolinamide Fungicide Targeting on the Cytochrome bc1 Complex and Its Structural Modification.

Picolinamide fungicides, structurally related to UK-2A and antimycin-A, bind into the Qi-site in the bc1 complex. However, the detailed binding mode of picolinamide fungicides remains unknown. In the present study, antimycin-A and UK-2A were selected to study the binding mode of picolinamide inhibitors with four protonation states in the Qi-site by integrating molecular dynamics simulation, molecular docking, and molecular mechanics Generalized Born surface area (MM/GBSA) calculations. Subsequently, a series of new picolinamide derivatives were designed and synthesized to further understand the effects of substituents on the tail phenyl ring. The computational results indicated that the substituted aromatic rings in antimycin-A and UK-2A were the pharmacophore fragments and made the primary contribution when bound to a protein. Compound 9g-hydrolysis formed H-bonds with Hie201 and Ash228 and showed an IC50 value of 6.05 ± 0.24 µM against the porcine bc1 complex. Compound 9c, with a simpler chemical structure, showed higher control effects than florylpicoxamid against cucumber downy mildew and expanded the fungicidal spectrum of picolinamide fungicides. The structural and mechanistic insights obtained from the present study will provide a valuable clue for the future designing of new promising Qi-site inhibitors.

Nitazoxanide reduces inflammation and bone erosion in mice with collagen-induced arthritis via inhibiting the JAK2/STAT3 and NF-κB pathways in fibroblast-like synoviocytes.

Our recent study showed that Nitazoxanide (NTZ), an FDA-approved anti-parasitic drug, prevents ovariectomy-induced bone loss by inhibiting osteoclast activity. However, there have been no investigations to determine whether NTZ has preventive potential in other bone resorbing diseases, especially rheumatoid arthritis (RA). In this study, the primary RA fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) murine model were used to evaluate the effect of NTZ. The results showed that NTZ potently inhibited proliferation, migration and invasion capacity of RA-FLS in a dose dependent manner by restraining cell entry into S phases, without induction of cell apoptosis. NTZ obviously reduced spontaneous mRNA expression of IL-1ß, IL-6 and RANKL, as well as TNF-α-induced transcription of the IL-1ß, IL-6, and MMP9 genes. In terms of molecular mechanism, NTZ significantly inhibited the basal or TNF-α-induced activation of JAK2/STAT3 (T705) and NF-κB pathway, but not MAPK and STAT3 (S727) phosphorylation. Moreover, NTZ ameliorated synovial inflammation and bone erosion in CIA mice through reducing the production of inflammatory mediators and osteoclast formation, respectively. Collectively, our findings indicate that NTZ exhibits anti-inflammatory and anti-erosive effects both ex vivo and in vivo, which provides promising evidence for the therapeutic application of NTZ as a novel therapeutic agent for RA.

Seizure Pathways Changes at the Subject-Specific Level via Dynamic Step Effective Network Analysis.

The variability in the propagation pathway in epilepsy is a main factor contributing to surgical treatment failure. Ways to accurately capture the brain propagation network and quantitatively assess its evolution remain poorly described. This work aims to develop a dynamic step effective network (dSTE) to obtain the propagation path network of multiple seizures in the same patient and explore the degree of dissimilarity. Multichannel stereo-electroencephalography (sEEG) signals were acquired with ictal processes involving continuous changes in information propagation. We utilized high-order dynamic brain networks to obtain propagation networks through different levels of linking steps. We proposed a dissimilarity index based on singular value decomposition to quantitatively compare seizure pathways. Simulated data were generated through The Virtual Brain, and the reliability of this method was verified through ablation experiments. By applying the proposed method to two datasets consisting of 29 patients total, the evolution processes of each patient's seizure networks was obtained, and the within-patient dissimilarities were quantitatively compared. Finally, three types of brain network connectivity patterns were found. Type I patients have a good prognosis, while type III patients are prone to postoperative recurrence. This method captures the evolution of seizure propagation networks and assesses their dissimilarity more reliably than existing methods, demonstrating good robustness for studying the propagation path differences for multiple seizures in epilepsy patients. The three different patterns will be important considerations when planning epilepsy surgery under sEEG guidance.

Results and analysis of examination doses for paediatric CT procedures based on a nationwide survey in China.

OBJECTIVE: To report the results of a dose survey conducted across 31 provinces in mainland China from 2017 to 2018 and to analyse the dose level to determine the national diagnostic reference levels (DRLs) for paediatric CT procedures. METHODS: At least ten patients for each age group (0- < 1, 1- < 5, 5- < 10, 10- < 15 years) and each procedure (head, chest and abdomen) for each CT scanner were selected from four to eight hospitals in each province. The dose information (CTDIvol and DLP) was collected from the HIS or RIS-PACS systems. The median values in each CT scanner were considered the representative dose values for the paediatric patients in CT scanning. The national DRLs were estimated based on the 75th percentile distribution of the median values. RESULTS: A total of 24,395 patients and 319 CT scanners were investigated across 262 hospitals. For paediatric CT scanning in 4 different age groups, the median (P50) and the 75th percentile (P75) of CTDIvol and DLP for each scanning procedure were calculated and reported. National DRLs were then proposed for each procedure and age group. CONCLUSION: The dose level of CT scanning for children in mainland China was reported for the first time. The DRLs for paediatric CT in the present study are similar to those in some Asian countries but higher than those in European countries. CLINICAL RELEVANCE STATEMENT: The paediatric CT is an extensively used tool in diagnosing paediatric disease; however, children are more sensitive to radiation. Establishing the diagnostic reference level of paediatric CT examination is necessary to reduce the dose of CT in children and promote the optimisation of medical exposure. KEY POINTS: • The DRLs for 3 paediatric CT procedures (head, chest and abdomen) and 4 age groups (0- < 1, 1- < 5, 5- < 10, 10- < 15 years) were proposed in mainland China first time. • The examination parameter and dose for children need to be further optimised in China, especially to lower the tube voltage in paediatric CT.