Artificial intelligence-based prognostic model accurately predicts the survival of patients with diffuse large B-cell lymphomas: analysis of a large cohort in China.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) display high molecular heterogeneity, but the International Prognostic Index (IPI) considers only clinical indicators and has not been updated to include molecular data. Therefore, we developed a widely applicable novel scoring system with molecular indicators screened by artificial intelligence (AI) that achieves accurate prognostic stratification and promotes individualized treatments. METHODS: We retrospectively enrolled a cohort of 401 patients with DLBCL from our hospital, covering the period from January 2015 to January 2019. We included 22 variables in our analysis and assigned them weights using the random survival forest method to establish a new predictive model combining bidirectional long-short term memory (Bi-LSTM) and logistic hazard techniques. We compared the predictive performance of our "molecular-contained prognostic model" (McPM) and the IPI. In addition, we developed a simplified version of the McPM (sMcPM) to enhance its practical applicability in clinical settings. We also demonstrated the improved risk stratification capabilities of the sMcPM. RESULTS: Our McPM showed superior predictive accuracy, as indicated by its high C-index and low integrated Brier score (IBS), for both overall survival (OS) and progression-free survival (PFS). The overall performance of the McPM was also better than that of the IPI based on receiver operating characteristic (ROC) curve fitting. We selected five key indicators, including extranodal involvement sites, lactate dehydrogenase (LDH), MYC gene status, absolute monocyte count (AMC), and platelet count (PLT) to establish the sMcPM, which is more suitable for clinical applications. The sMcPM showed similar OS results (P < 0.0001 for both) to the IPI and significantly better PFS stratification results (P < 0.0001 for sMcPM vs. P = 0.44 for IPI). CONCLUSIONS: Our new McPM, including both clinical and molecular variables, showed superior overall stratification performance to the IPI, rendering it more suitable for the molecular era. Moreover, our sMcPM may become a widely used and effective stratification tool to guide individual precision treatments and drive new drug development.

In silico and in vivo discovery of antioxidant sea cucumber peptides with antineurodegenerative properties.

Since oxidative stress is often associated with neurodegenerative diseases, antioxidants are likely to confer protection against neurodegeneration. Despite an increasing number of food-derived peptides being identified as antioxidants, their antineurodegenerative potentials remain largely unexplored. Here, a sea cucumber peptide preparation - the peptide-rich fraction of <3 kDa (UF<3K) obtained by ultrafiltration from Apostichopus japonicus protein hydrolyzate - was found to protect PC12 cells and Caenorhabditis elegans from neurodegeneration by reducing oxidative stress and apoptosis, demonstrating its in vitro and in vivo neuroprotective effects. As many food-originated peptides are cryptides (cryptic peptides - short amino acid sequences encrypted in parent proteins) released in quantities by protein hydrolysis, UF<3K was subjected to sequencing analysis. As expected, a large repertoire of peptides were identified in UF<3K, establishing a sea cucumber cryptome (1238 peptides in total). Then 134 peptides were randomly selected from the cryptome (>10%) and analyzed for their antioxidant activities using a number of in silico bioinformatic programs as well as in vivo experimental assays in C. elegans. From these results, a novel antioxidant peptide - HoloPep#362 (FETLMPLWGNK) - was shown to not only inhibit aggregation of neurodegeneration-associated polygluatmine proteins but also ameliorate behavioral deficits in proteotoxicity nematodes. Proteomic analysis revealed an increased expression of several lysosomal proteases by HoloPep#362, suggesting proteostasis maintenance as a mechanism for its antineurodegenerative action. These findings provide an insight into the health-promoting potential of sea cucumber peptides as neuroprotective nutraceuticals and also into the importance of training in silico peptide bioactivity prediction programs with in vivo experimental data.

LncRNA RGMB-AS1 inhibits HMOX1 ubiquitination and NAA10 activation to induce ferroptosis in non-small cell lung cancer.

Ferroptosis, an iron-dependent regulated cell death caused by excessive lipid peroxide accumulation, has emerged as a promising therapeutic target in various cancers, including non-small cell lung cancer (NSCLC). In this study, we identified the long non-coding RNA RGMB-AS1 as a key regulator of ferroptosis in NSCLC. Mechanistically, RGMB-AS1 interacted with heme oxygenase 1 (HMOX1) and prevented its ubiquitination by the E3 ligase TRC8, leading to increased HMOX1 stability and enhanced ferroptosis. Additionally, RGMB-AS1 bound to the 82-87 amino acid region of N-alpha-acetyltransferase 10 (NAA10), stimulating its acetyltransferase activity and promoting the conversion of acetyl-CoA to HMG-CoA, further contributing to ferroptosis. The RGMB-AS1-HMOX1 and RGMB-AS1-NAA10 axes synergistically inhibited NSCLC growth both in vitro and in vivo. Clinically, low RGMB-AS1 expression was associated with advanced tumor stage and poor overall survival in NSCLC patients. Furthermore, adeno-associated virus-mediated RGMB-AS1 overexpression significantly suppressed tumor growth in mouse xenograft models. Our findings uncover a novel lncRNA-mediated regulatory mechanism of ferroptosis and highlight the potential of RGMB-AS1 as a prognostic biomarker and therapeutic target in NSCLC.

Association of Monocyte-to-HDL Cholesterol Ratio with Endothelial Dysfunction in Patients with Type 2 Diabetes.

Aims: To explore the relationship between monocyte-to-HDL cholesterol ratio (MHR) and endothelial function in patients with type 2 diabetes (T2DM). Methods: 243 patients diagnosed with T2DM were enrolled in this cross-sectional study. Patients were divided into two groups by flow-mediated dilation (FMD) quintile as nonendothelial dysfunction (FMD ≥ 6.4%) and endothelial dysfunction (FMD < 6.4%). The relationship between MHR and FMD was analyzed using Spearman's correlation, partial correlation, and multiple logistic regression analysis. ROC curve was fitted to evaluate the ability of MHR to predict endothelial dysfunction. Results: Endothelial dysfunction was present in 193 (79%) patients. Patients with endothelial dysfunction had higher MHR (p < 0.05) than those without endothelial dysfunction. Furthermore, MHR had a significantly positive correlation with endothelial dysfunction (r = 0.17, p < 0.05), and the positive association persisted even after controlling for confounding factors (r = 0.14, p < 0.05). Logistic regression showed that MHR was an independent contributor for endothelial dysfunction (OR: 1.35 (1.08, 1.70), p < 0.05) and the risk of endothelial dysfunction increases by 61% with each standard deviation increase in MHR (OR: 1.61 (1.12, 2.30), p < 0.05) (model 1). After adjusting for sex, age, BMI, disease course, hypertension, smoking, and drinking (model 2) as well as HbA1c, HOMA-IR, C-reactive protein, and TG (model 3), similar results were obtained. In ROC analysis, the area of under the ROC curve (AUC) for MHR was 0.60 (95% CI 0.52-0.69, p < 0.05). Conclusion: MHR was independently associated with endothelial dysfunction in T2DM patients. It could be a new biomarker for vascular endothelial function assessment.

Identification and assessment of new PIM2 inhibitors for treating hematologic cancers: A combined approach of energy-based virtual screening and machine learning evaluation.

PIM2, part of the PIM kinase family along with PIM1 and PIM3, is often overexpressed in hematologic cancers, fueling tumor growth. Despite its significance, there are no approved drugs targeting it. In response to this challenge, we devised a thorough virtual screening workflow for discovering novel PIM2 inhibitors. Our process includes molecular docking and diverse scoring methods like molecular mechanics generalized born surface area, XGBOOST, and DeepDock to rank potential inhibitors by binding affinities and interaction potential. Ten compounds were selected and subjected to an adequate evaluation of their biological activity. Compound 2 emerged as the most potent inhibitor with an IC50 of approximately 135.7 nM. It also displayed significant activity against various hematological cancers, including acute myeloid leukemia, mantle cell lymphoma, and anaplastic large cell lymphoma (ALCL). Molecular dynamics simulations elucidated the binding mode of compound 2 with PIM2, offering insights for drug development. These results highlight the reliability and efficacy of our virtual screening workflow, promising new drugs for hematologic cancers, notably ALCL.

Chondroitin Sulfate Improves Mechanical Properties of Gelatin Hydrogel for Cartilage Regeneration in Rats.

Cartilage injury is a common disease in daily life. Especially in aging populations, the incidence of osteoarthritis is increasing. However, due to the poor regeneration ability of cartilage, most cartilage injuries cannot be effectively repaired. Even cartilage tissue engineering still faces many problems such as complex composition and poor integration of scaffolds and host tissues. In this study, chondroitin sulfate, one of the main components of extracellular matrix (ECM), is chosen as the main natural component of the material, which can protect cartilage in a variety of ways. Moreover, the results show that the addition of chondroitin sulfate improves the mechanical properties of gelatin methacrylate (GelMA) hydrogel, making it able to effectively bear mechanical loads in vivo. Further, chondroitin sulfate is modified to obtain the oxidized chondroitin sulfate (OCS) containing aldehyde groups via sodium periodate. This special group improves the interface integration and adhesion ability of the hydrogel to host cartilage tissue through schiff base reactions. In summary, GelMA/OCS hydrogel is a promising candidate for cartilage regeneration with good biocompatibility, mechanical properties, tissue integration ability, and excellent cartilage repair ability.

Deciphering and advancing CAR T-cell therapy with single-cell sequencing technologies.

Chimeric antigen receptor (CAR) T-cell therapy has made remarkable progress in cancer immunotherapy, but several challenges with unclear mechanisms hinder its wide clinical application. Single-cell sequencing technologies, with the powerful unbiased analysis of cellular heterogeneity and molecular patterns at unprecedented resolution, have greatly advanced our understanding of immunology and oncology. In this review, we summarize the recent applications of single-cell sequencing technologies in CAR T-cell therapy, including the biological characteristics, the latest mechanisms of clinical response and adverse events, promising strategies that contribute to the development of CAR T-cell therapy and CAR target selection. Generally, we propose a multi-omics research mode to guide potential future research on CAR T-cell therapy.

Tyrosol attenuates lipopolysaccharide­induced inflammation in HUVECs to promote vascular health against atherosclerosis challenge.

The role of vascular endothelial cells in acute and chronic vascular inflammatory response has long been recognized. Therefore, persistent vascular inflammation may lead to endothelial dysfunction, thus resulting in the release of pro-inflammatory cytokines and the expression of adhesion molecules, which in turn promote monocyte/macrophage adhesion. Inflammation serves a key role in the development of vascular diseases, such as atherosclerosis. Tyrosol is a natural polyphenolic compound with diverse biological functions, found in large quantities in olive oil or in Rhodiola rosea. The current study aimed to investigate the regulatory in vitro effects of tyrosol on pro-inflammatory phenotypes using Cell Counting Kit-8, cell adhesion assay, wound healing, ELISA, western blotting, duel-luciferase, reverse transcription-quantitative PCR and flow cytometry. The results showed that tyrosol significantly inhibited the adhesion of THP-1 human umbilical vein endothelial cells, reduced lipopolysaccharide-induced cell migration and decreased the release of pro-inflammatory factors and the expression levels of adhesion-related molecules, such as TNF-α, monocyte chemotactic protein-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Previous studies indicate that NF-κB could serve a pivotal role in initiating the inflammatory responses of endothelial cells and particularly in regulating the expression of adhesion molecules and inflammatory factors. The results of the current study demonstrated that tyrosol was associated with decreased expression of adhesion molecules and monocyte-endothelial cell adhesion, thus suggesting that tyrosol could be a novel pharmacological approach for treating inflammatory vascular diseases.

Mammary Paget's Disease of Young Females: Case Reports and Comparison With Middle-Aged and Elderly Patients.

Purpose: Mammary Paget's disease (PD) in young women has seldom been reported. The aim of this study was to improve the knowledge of the clinicopathological characteristics in young patients with PD to provide a basis for the precise treatment of young patients. Methods: The medical records and pathological slides of 8 young patients (younger than 40 years old) with PD were reviewed. The data of 20 patients over 40 years old within the same period were used as controls. Results: The average age was 32.00 ± 3.96 years for the young patient group, with the youngest aged 27 years. The first symptom, physical examination, Paget cell morphology, and immunohistochemical marks were the same in different age groups. But young patients have varied tumor distribution patterns, fewer interstitial inflammatory cells, and advanced pathological local lymphatic metastasis than older patients in the same period. Conclusions: PD in young women has unique histopathological features. These manifestations seem to provide personalized treatment for PD treatment in young patients. More research is needed to clarify the significance of this research.

Peripheral immune cell profiling of double-hit lymphoma by mass cytometry.

BACKGROUND: Double-hit or Triple-hit lymphoma (DHL/THL) is a subset of high-grade B cell lymphoma harboring rearrangements of MYC and BCL2 and/or BCL6, and usually associate with aggressive profile, while current therapies tend to provide poor clinical outcomes and eventually relapsed. Further explorations of DHL at cellular and molecular levels are in demand to offer guidance for clinical activity. METHODS: We collected the peripheral blood of DHL patients and diffused large B cell lymphoma (DLBCL) patients from single institute and converted them into PBMC samples. Mass cytometry was then performed to characterize these samples by 42 antibody markers with samples of healthy people as control. We divided the immune cell subtypes based on the expression profile of surface antigens, and the proportion of each cell subtype was also analyzed. By comparing the data of the DLBCL group and the healthy group, we figured out the distinguished immune cell subtypes of DHL patients according to their abundance and marker expression level. We further analyzed the heterogeneity of DHL samples by pairwise comparison based on clinical characteristics. RESULTS: We found double-positive T cells (DPT) cells were in a significantly high percentage in DHL patients, whereas the ratio of double-negative T cells (DNT) was largely reduced in patients. Besides, CD38 was uniquely expressed at a high level on some naïve B cells of DHL patients, which could be a marker for the diagnosis of DHL (distinguishing from DLBCL), or even be a drug target for the treatment of DHL. In addition, we illustrated the heterogeneity of DHL patients in terms of immune cell landscape, and highlighted TP53 as a major factor that contributes to the heterogeneity of the T cells profile. CONCLUSION: Our study demonstrated the distinct peripheral immune cell profile of DHL patients by contrast to DLBCL patients and healthy people, as well as the heterogeneity within the DHL group, which could provide valuable guidance for the diagnosis and treatment of DHL.

Can radiomics replace the SPARCC scoring system in evaluating bone marrow edema of sacroiliac joints in patients with axial spondyloarthritis?

OBJECTIVES: To develop an objective and efficient method based on radiomics to evaluate bone marrow edema (BMO) of sacroiliac joints (SIJs) by magnetic resonance imaging (MRI) in patients with axial spondyloarthritis (axSpA) and to compare with the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. METHODS: From September 2013 to March 2022, patients with axSpA who underwent 3.0T SIJ-MRI were included and were randomly divided into training and validation cohorts at a ratio of 7:3. The optimal radiomics features selected from the SIJ-MRI in the training cohort were included to generate the radiomics model. The performance of the model was evaluated by ROC analysis and decision curve analysis (DCA). Rad scores were calculated using the radiomics model. The responsiveness was compared for Rad scores and SPARCC scores. We also assessed the correlation between the Rad score and SPARCC score. RESULTS: A total of 558 patients were finally included. The radiomics model showed favorable discrimination of a SPARCC score <2 or ≥2 both in the training (AUC, 0.90; 95% CI: 0.87-0.93) and validation cohorts (AUC, 0.90; 95% CI, 0.86-0.95). DCA confirmed that the model was clinically useful. Rad score showed higher responsiveness to treatment-related change than SPARCC score. Furthermore, a significant correlation was noted between the Rad score and SPARCC score when scoring the status of BMO (rs=0.80, P < 0.001), and a strong correlation was noted when scoring the change in BMO (r=0.70, P < 0.001). CONCLUSION: The study proposed a radiomics model to accurately quantify the BMO of SIJs in patients with axSpA, providing an alternative to the SPARCC scoring system. Key Points • The Rad score is an index with high validity for the objective and quantitative evaluation of bone marrow edema (BMO) of the sacroiliac joints in axial spondyloarthritis. • The Rad score is a promising tool to monitor the change of BMO upon treatment.

Astragalus polysaccharide ameliorates vascular endothelial dysfunction by stimulating macrophage M2 polarization via potentiating Nrf2/HO-1 signaling pathway.

BACKGROUND: Oxidative stress and chronic non-infectious inflammation caused vascular endothelial dysfunction (VED) is a critical and initiating factor in Type 2 diabetes induced vascular complications, while macrophage polarization plays a regulatory role in VED. Astragalus polysaccharide (APS) has been widely used for treating diabetic vascular diseases, but its mechanisms of action have not been fully elucidated. PURPOSE: This study aimed to investigate the modulatory effects of APS on macrophage polarization and to reveal the potential mechanisms of APS in LPS and HG stimulated macrophages and diabetic model rats. METHODS: In vitro and in vivo studies were used to explore the mechanism of APS. The macrophage polarization and reactive oxygen species (ROS) release was monitored by flow cytometry and the associated inflammatory factors were detected by ELISA. For oxidative stress regulatory pathway detection, protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) was measured by Western blotting. The vascular endothelial functions were measured by transwell, tube formation assay, scratch assay, adhesion assay. The thoracic aorta pathological changes were evaluated by Haematoxylin-eosin and immunohistochemistry. RESULTS: In vitro, APS inhibited the LPS/HG-stimulated THP-1 macrophage differentiated into macrophage M1, coupling with reduction in the ROS production and pro-inflammatory factors (TNF-α, IL-6, IL-12) release. Furthermore, endothelial cells proliferation and apoptosis were ameliorated after APS treatment. Meanwhile, APS-treated THP-1/macrophage occurred a differentiation into M2 polarization and anti-inflammatory factors (IL-4, IL-10, and Arg-1) release via enhancing Nrf2/HO-1 signaling pathway, which could be disturbed by using siNrf2. APS promoted the migration and angiogenesis of endothelial cells in co-cultured of HUVECs and macrophages under high glucose. Finally, similar results were observed in vivo, APS alleviated thoracic aorta complications of diabetic rats accompanied by a remarkable reduction in inflammation and an increased in the number of anti-inflammatory macrophage polarization. CONCLUSION: Our results demonstrated that APS ameliorated vascular endothelial dysfunction in diabetes by stimulating macrophage polarization to M2 via enhancing the Nrf2/HO-1 pathway.

Berberine inhibits gluconeogenesis in spontaneous diabetic rats by regulating the AKT/MAPK/NO/cGMP/PKG signaling pathway.

This work was aimed to investigate the action mechanism of berberine (BBR) on gluconeogenesis. The effects of BBR were examined in rat primary hepatocytes and confirmed in vivo in spontaneous diabetic rats. Protein levels were assessed by Western blot. Immunofluorescence staining was utilized for visualizing protein expression, while qRT-PCR helped for the determination of gene expression at the mRNA level. Besides, cGMP concentration was measured using ELISA, whereas NO level was assessed by spectrophotometry. BBR inhibited gluconeogenesis by downregulating G6Pase and PEPCK via inhibition of CREB phosphorylation. Moreover, BBR enhanced NO and cGMP concentrations, leading to the activation of the NO/cGMP/PKG signaling via activating AKT1/MAPK axis. The in vivo experiments were consistent with the findings obtained in vitro. Hence, BBR represents a drug candidate for diabetic patients and its mechanism of action may be driven via the AKT/MAPK/NO/cGMP/PKG pathway.

Effect of integrin α7 on cell proliferation, invasion, apoptosis and the PI3K/AKT pathway, and its association with clinicopathological features in endometrial cancer.

Targeting integrin α7 (ITGA7) suppresses malignant progression of several types of cancer, including tongue squamous cell carcinoma, hepatocellular carcinoma and non-small cell lung cancer, while the effect of its knockdown on cell function and its association with clinicopathological features in endometrial cancer (EC) is unclear. The present study aimed to investigate this issue. ITGA7 was knocked down by short-interfering (si)RNA in Ishikawa and RL95-2 cells followed by western blotting and reverse transcription-quantitative PCR assays. Subsequently, cell proliferation, apoptosis, invasion and expression levels of PI3K, phosphorylated (p-) PI3K, AKT and p-AKT were determined using Cell Counting Kit-8, TUNEL, Transwell assays and western blotting. Moreover, ITGA7 in tumor and adjacent tissues from 50 patients with endometrial cancer was detected using immunohistochemical assay. ITGA7 expression was increased in EC cell lines (HEC-1A, RL95-2, Ishikawa and KLE) compared with telomerase-immortalized human endometrial stromal cells (THESCs). In both Ishikawa and RL95-2 cells, three ITGA7 siRNAs all demonstrated good efficiency on ITGA7 knockdown, amongst which the one with the highest efficiency was selected for the following experiments. ITGA7 knockdown reduced cell proliferation and invasion, while inducing apoptosis; moreover, it suppressed p-PI3K/PI3K and p-AKT/AKT ratios. In patients with EC, ITGA7 expression was increased in tumor tissues compared with adjacent tissues, and its lower tumor expression was associated with myometrial invasion (<1/2), non-lymphovascular invasion and decreased FIGO stage. In conclusion, ITGA7 knockdown repressed proliferation, invasion and the PI3K/AKT pathway while inducing apoptosis in EC cell lines, and its insufficiency was associated with less advanced tumor features in EC patients. These results indicated that ITGA7 may be a potential target for the treatment of EC.

Epothilone B inactivation of Sirtuin1 promotes mitochondrial reactive oxygen species to induce dysfunction and ferroptosis of Schwann cells.

Epothilone B (EpoB) is an FDA-approved anti-neoplastic agent used to treat metastatic breast cancer; However, its usage is limited due to its severe peripheral neurotoxicity. Ferroptosis is a type of programmed cell death triggered by iron accumulation, and it is induced by lipid peroxidation. Ferroptosis has been linked to multiple diseases, including cancer, type 2 diabetes, and neurodegenerative disorders. Here, we assessed the role of ferroptosis in EpoB-induced neural dysfunction. Our results revealed that EpoB induced ferroptosis, which was significantly reduced by the ferroptosis inhibitor Fer-1. In addition, EpoB decreased the mitochondrial membrane potential and the cytochrome c levels in Schwann cells (SCs). The antioxidant MitoTEMPO, which targets the mitochondria, reduced ferroptosis brought on by EpoB. Moreover, we demonstrated that in vivo EpoB-induced myelin degradation and neuronal dysfunction were mitigated by SRT1720, a Sirtuin1 (SIRT1) activator, and by SRT1720 and mitoquinone mesylate (mitoQ). Our results suggest that ferroptosis elicited by EpoB is caused by mitochondrial damage mediated by SIRT1 inactivation and that ferroptosis causes neural dysfunction following EpoB.

Construction of Molecular Subtype and Prognosis Prediction Model of Osteosarcoma Based on Aging-Related Genes.

Background: Osteosarcoma (OS) is a rare form of malignant bone cancer that is usually detected in young adults and adolescents. This disease shows a poor prognosis owing to its metastatic status and resistance to chemotherapy. Hence, it is necessary to design a risk model that can successfully forecast the OS prognosis in patients. Methods: The researchers retrieved the RNA sequencing data and follow-up clinical data related to OS patients from the TARGET and GEO databases, respectively. The coxph function in R software was used for carrying out the Univariate Cox regression analysis for deriving the aging-based genes related sto the OS prognosis. The researchers conducted consistency clustering using the ConcensusClusterPlus R package. The R software package ESTIMATE, MCPcounter, and GSVA packages were used for assessing the immune scores of various subtypes using the ssGSEA technique, respectively. The Univariate Cox and Lasso regression analyses were used for screening and developing a risk model. The ROC curves were constructed, using the pROC package. The performance of their developed risk model and designed survival curve was conducted, with the help of the Survminer package. Results: The OS patients were classified into 2 categories, as per the aging-related genes. The results revealed that the Cluster 1 patients showed a better prognosis than the Cluster 2 patients. Both clusters showed different immune microenvironments. Additional screening of the prognosis-associated genes revealed the presence of 5 genes, i.e., ERCC4, GPX4, EPS8, TERT, and STAT5A, and these data were used for developing the risk model. This risk model categorized the training set samples into the high- and low-risk groups. The patients classified into the high-risk group showed a poor OS prognosis compared to the low-risk patients. The researchers verified the reliability and robustness of the designed 5-gene signature using the internal and external datasets. This risk model was able to effectively predict the prognosis even in the samples having differing clinical features. Compared with other models, the 5- gene model performs better in predicting the risk of osteosarcoma. Conclusion: The 5-gene signature developed by the researchers in this study could be effectively used for forecasting the OS prognosis in patients.

Clinical safety study of photobiomodulation in acute spinal cord injury by scattering fiber.

The study aimed to design a reliable and straightforward PBM method by implanting a medical scattering fiber above surgically exposed spinal cord in SCI patients. Moreover, the safety of this method was examined. Twelve patients with acute SCI (ASIA B) requiring posterior decompression were recruited. The medical scattering fiber was implanted above the spinal cord, and was continuously irradiated at 810 nm, 300 mW, 30 min/day, once per day for 7 days. The vital signs (temperature, blood pressure, respiratory rate, heart rate, and oxygen saturation), infection indicators (WBC, NEUT, hs-CRP, and PCT), photo-allergic reaction indicators (Eosinophil and Basophil), coagulation function indicators (PT, APTT, TT) and neurological stability indicators (ASIA sensory and motor scores) were recorded to evaluate the safety of PBM. Three months after surgery, 12 patients completed follow-up. In our study, direct PBM on SCI site did not cause clinically pathologic changes in vital signs of the patients. All patients had higher WBC, NEUT, and hs-CRP at day 3 during irradiation than those before surgery, and returned to normal at day 7. The changes in Eosinophil and Basophil that were closely associated with allergic reactions were within normal limits throughout the course of irradiation. The coagulation function (PT, APTT, and TT) of patients were also in the normal range. The ASIA sensory and motor scores of all patients had no changes throughout the irradiation process. However, in the follow-up, both ASIA sensory and motor scores of all patients had minor improvement than those in pre-irradiation, and 7 patients had adverse events, but they were not considered to be related to PBM. Our study might firstly employ direct PBM in the SCI by using scattered optical fibers. In a limited sample size, our study concluded that direct PBM at the site of SCI would not produce adverse effects within the appropriate irradiation parameters. The method is safe, feasible, and does not add additional trauma to the patient. Our preliminary study might provide a new methodology for the clinical PBM treatment of acute SCI.

Development and Validation of a Nomogram for Predicting Generalization in Patients With Ocular Myasthenia Gravis.

Background: This study aims to develop and validate a nomogram for predicting 1- and 2-year generalization probabilities in patients with ocular myasthenia gravis (OMG). Methods: In total, 501 eligible patients with OMG treated at seven tertiary hospitals in China between January 2015 and May 2019 were included. The primary outcome measure was disease generalization. A nomogram for predicting 1- and 2-year generalization probabilities was constructed using a stepwise Cox regression model. Nomogram performance was quantified using C-indexes and calibration curves. Two-year cumulative generalization rates were analyzed using the Kaplan-Meier method for distinct nomogram-stratified risk groups. The clinical usefulness of the nomogram was evaluated using decision curve analysis (DCA). Result: The eligible patients were randomly divided into a development cohort (n=351, 70%) and a validation cohort (n=150, 30%). The final model included five variables: sex, onset age, repetitive nerve stimulation findings, acetylcholine receptor antibody test results, and thymic status. The model demonstrated good discrimination (C-indexes of 0.733 and 0.788 in the development and validation cohorts, respectively) and calibration, with good agreement between actual and nomogram-estimated generalization probabilities. Kaplan-Meier curves revealed higher 2-year cumulative generalization rates in the high-risk group than that in the low-risk group. DCA demonstrated a higher net benefit of nomogram-assisted decisions compared to treatment of all patients or none. Conclusion: The nomogram model can predict 1- and 2-year generalization probabilities in patients with OMG and stratified these patients into distinct generalization risk groups. The nomogram has potential to aid neurologists in selecting suitable patients for initiating immunotherapy and for enrolment in clinical trials of risk-modifying treatments.

CircWDR26 regulates endometrial carcinoma progression via miR-212-3p-mediated typing genes MSH2.

BACKGROUND: Circular RNAs (circRNA) are important in mediating tumor progression, but their roles in endometrial carcinoma (EC) are not fully understood yet. Many circRNAs are dysregulated and may contribute to EC progression. The functions of circWDR26 in EC remain unknown. METHODS: The expression of circWDR26 in EC and adjacent normal tissues, and cell lines was determined by qPCR. The proliferation, apoptosis, migration, and invasion of EC cells was examined by CCK-8 assay, flow cytometry, wound healing assay and Transwell assay. The interaction between circWDR26, MSH2 and miR-212-3p was determined by luciferase assay. EC cells were inoculated into nude mice and tumor burden was determined by measuring tumor dimensions, size, and weight. The proliferative marker Ki67 in EC tissue was determined by immunohistochemistry. RESULTS: The expression of circWDR26 in EC tissues or cell lines was higher than in the normal tissue or endometrial epithelial cells. Downregulation of circWDR26 resulted in attenuated proliferation, increased apoptosis, reduced migration and invasion of EC cells. Mechanistically, circWDR26 targeted and suppressed the expression of miR-212-3p. We further found that MSH2 was the novel target of miR-212-3p and was upregulated by circWDR26 via inhibiting miR-212-3p. In vivo experiment demonstrated that circWDR26 was essential for EC tumor growth. CONCLUSION: circWDR26 promoted EC progression by regulating miR-212-3p/MSH2 axis and provided novel insights into anti-cancer treatment.

The Relationship Between Baseline Cortisol Levels and Surgery Method of Primary Bilateral Macronodular Adrenal Hyperplasia.

Aim was to explore the associations between baseline cortisol levels and surgery method of primary bilateral macronodular adrenal hyperplasia (PBMAH). We retrospectively reviewed the clinical features and management of 30 patients (18 females and 12 males) who were diagnosed with PBMAH in our center between 2005 and 2019. Based on surgery method, we divided the patients into two groups: unilateral adrenalectomy (UA) group; and bilateral adrenalectomy (BA) group. Serum cortisol rhythm and 24-hour urinary free cortisol (UFC/24 h) levels were assayed using chemiluminescence method. Associations between baseline cortisol levels and BA were assessed using logistic regression. The predictive value of baseline cortisol levels for BA was calculated using receiver operating characteristic (ROC) curves. Twenty patients (66.7%) underwent UAs and ten patients (33.3%) underwent BAs. After adjusting for age, sex, BMI, SBP, and adrenal volume, the concentrations of baseline serum cortisol (8 AM, 4 PM, and 0 AM) and UFC/24 h were associated with bilateral adrenalectomy (all p<0.05). The area under the ROC curve based on 8 AM serum cortisol level model was larger than that in models based on 4 PM, 0 AM serum cortisol levels and UFC/24 h, but the differences were non-significant (all p>0.05). According to maximum Youden index criteria, the optimal cutoffs of 8 AM serum cortisol level and UFC were 26.89 µg/dl and 406.65 µg/24 h, respectively, for BA. The baseline cortisol levels are positively associated with BA. Increased levels of baseline cortisol levels may predict higher possibility of BA, which should be confirmed by prospective studies.