Functional roles of circular RNAs in lung injury.

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury.

Near-infrared fluorescent probe for detection of hydrogen sulfide in water samples and food spoilage.

Hydrogen sulfide (H2S) is a common toxic gas that threatens the quality and safety of environmental water and food. Herein, a new near-infrared fluorescent probe DTCM was synthesized and characterized by single crystal X-ray diffraction for sensing H2S. It exhibited a remarkable "turn-on" near-infrared (NIR) emission response at 665 nm with a remarkably massive Stokes shift of 175 nm, super-rapid detection ability (within 30 s), excellent photostability, high selectivity and sensitivity (limit of detection, LOD = 58 nM). Additionally, the probe was successfully utilized for the detection of H2S in environmental water samples. The DTCM-loaded test papers enabled convenient and real-time monitoring of H2S produced by food spoilage.

Human herpesvirus-6 infection in a critically ill and immunocompetent patient: a case report.

BACKGROUND: Human herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series. CASE PRESENTATION: In this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively. CONCLUSION: This case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient.

A Cross-Sectional and Longitudinal Integrated Study on Brain Functional Changes in a Neuropathic Pain Rat Model.

Human and animal imaging studies demonstrated that chronic pain profoundly alters the structure and the functionality of several brain regions and even causes mental dysfunctions such as depression and anxiety disorders. In this article, we conducted a multimodal study cross-sectionally and longitudinally, to evaluate how neuropathic pain affects the brain. Using the spared nerve injury (SNI) model which promotes long-lasting mechanical allodynia, results showed that neuropathic pain deeply modified the intrinsic organization of the brain functional network 2 weeks after injury. There are significant changes in the activity of the left thalamus (Th_L) and left olfactory bulb (OB_L) brain regions after SNI, as evidenced by both the blood oxygen level-dependent (BOLD) signal and c-Fos expression. Importantly, these changes were closely related to mechanical pain behavior of rats. However, it is worth noting that after morphine administration for analgesia, only the increased activity in the TH region is reversed, while the decreased activity in the OB region becomes more prominent. Functional connectivity (FC) and c-Fos correlation analysis further showed these two regions of interest (ROIs) exhibit different FC patterns with other brain regions. Our study comprehensively revealed the adaptive changes of brain neural networks induced by nerve injury in both cross-sectional and longitudinal dimensions and emphasized the abnormal activity and FC of Th_L and OB_L in the pathological condition. It provides reliable assistance in exploring the intricate mechanisms of diseases.

Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study.

OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). PATIENTS AND METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. CONCLUSION: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

Temporal trends in neurosurgical volume and length of stay in a public healthcare system: A decade in review with a focus on the COVID-19 pandemic.

Background: Over the past decade, neurosurgical interventions have experienced changes in operative frequency and postoperative length of stay (LOS), with the recent COVID-19 pandemic significantly impacting these metrics. Evaluating these trends in a tertiary National Health Service center provides insights into the impact of surgical practices and health policy on LOS and is essential for optimizing healthcare management decisions. Methods: This was a single tertiary center retrospective case series analysis of neurosurgical procedures from 2012 to 2022. Factors including procedure type, admission urgency, and LOS were extracted from a prospectively maintained database. Six subspecialties were analyzed: Spine, Neuro-oncology, Skull base (SB), Functional, Cerebrospinal fluid (CSF), and Peripheral nerve (PN). Mann-Kendall temporal trend test and exploratory data analysis were performed. Results: 19,237 elective and day case operations were analyzed. Of the 6 sub-specialties, spine, neuro-oncology, SB, and CSF procedures all showed a significant trend toward decreasing frequency. A shift toward day case over elective procedures was evident, especially in spine (P < 0.001), SB (tau = 0.733, P = 0.0042), functional (tau = 0.156, P = 0.0016), and PN surgeries (P < 0.005). Over the last decade, decreasing LOS was observed for neuro-oncology (tau = -0.648, P = 0.0077), SB (tau = -0.382, P = 0.012), and functional operations, a trend which remained consistent during the COVID-19 pandemic (P = 0.01). Spine remained constant across the decade while PN demonstrated a trend toward increasing LOS. Conclusion: Most subspecialties demonstrate a decreasing LOS coupled with a shift toward day case procedures, potentially attributable to improvements in surgical techniques, less invasive approaches, and increased pressure on beds. Setting up extra dedicated day case theaters could help deal with the backlog of procedures, particularly with regard to the impact of COVID-19.

Bronchobiliary fistula caused after percutaneous transhepatic biliary drainage treatment: A case report.

RATIONALE: Percutaneous transhepatic biliary drainage (PTBD) plays a significant role especially in the diagnosis and decompression of bile duct obstruction. However, it is associated with complications such as hemobilia, occlusion of drainage, bile leakage, and even bronchobiliary fistula (BBF). PATIENT CONCERNS AND DIAGNOSES: We herein describe a patient with a complication of BBF caused by long-term indwelling PTBD catheters. She underwent multiple operations including bilioenteric anastomosis, hepatic left lateral lobectomy, and long-term PTBD treatment. Her symptoms were mainly cough, fever, and yellow sputum and her diagnosis was confirmed by sputum culture (bilirubin detection was positive). INTERVENTIONS AND OUTCOMES: The patient recovered uneventfully by minimally invasive treatment, was discharged after 1 week of hospitalization, and the drainage tube was removed 2 weeks later. During 2 years of follow-up, no recurrence of BBF was observed. LESSONS: Patients with long-term indwelling PTBD catheters for biliary tract obstruction may lead to BBF. The treatment plan of BBF is tailored to the patient's individualized characteristics. And minimally invasive treatments might be an effective alternate way for the treatment of BBF. The accurate diagnosis, precision treatment, and multidisciplinary team play important roles in the treatment of BBF.

The risk factors, antimicrobial resistance patterns, and outcomes associated with extended-spectrum ß-lactamases-Producing pathogens in pediatric urinary tract infection.

BACKGROUND: Extended-spectrum ß-lactamases-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis (ESBL-producing-EKP) are an increasingly common cause of childhood urinary tract infection (UTI) worldwide. Recognizing the risk factors and antimicrobial resistance patterns may guide new management in this population. METHODS: This is a retrospective cohort study of over 5 years in Taiwan (2017-2021). Inclusion criteria are hospitalized pediatric patients with the discharge diagnosis of UTI caused by E. coli, Klebsiella pneumoniae, or Proteus mirabilis. ESBL-producing-EKP and non-ESBL-producing-EKP UTI cases were reviewed for characteristics, urinary isolate antibiotics resistance, and clinical outcomes. RESULTS: The incidence rate of ESBL-producing-EKP UTI increased over the study period (Overall incidence rate: 14.1 %, 46/327 patients). Recent antibiotic therapy in ≤6 months (X2 = 11.83, p < 0.01) and a preterm gestational history (X2 = 8.11, p < 0.05) were associated with an increased risk. The proportion of patients with these two risk factors for ESBL acquisition were 37.5 % (X2 = 9.08, p < 0.05). The co-resistance rate of ESBL-producing-EKP to other antimicrobial agents was 63.0 % for gentamicin, 56.5 % for trimethoprim-sulfamethoxazole, 52.2 % for ciprofloxacin, 4.3 % for amikacin, and 2.2 % for imipenem. The generalized linear model analysis identified a significantly longer length of stay (ß: 2.85; 95 % confidence interval [CI]: 1.14-4.56; p < 0.01) and intensive care unit duration (ß: 5.86; 95 % CI: 1.59-10.12; p < 0.01) among patients with ESBL-producing-EKP UTI. CONCLUSION: Amikacin should be considered as an alternative antimicrobial choice beyond carbapenems for ESBL-producing-EKP UTI, especially in the context of carbapenem-resistant E. coli/Klebsiella pneumoniae (CRE/CRKP) emergence.

Porcine reproductive and respiratory syndrome virus upregulates SMPDL3B to promote viral replication by modulating lipid metabolism.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a severe threat to the health of pigs globally. Host factors play a critical role in PRRSV replication. Using PRRSV as a model for genome-scale CRISPR knockout (KO) screening, we identified a host factor critical to PRRSV infection: sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B). Our findings show that SMPDL3B restricted PRRSV attachment, entry, replication, and secretion and that its depletion significantly inhibited PRRSV proliferation, indicating that SMPDL3B plays a positive role in PRRSV replication. Our data also show that SMPDL3B deficiency resulted in an accumulation of intracellular lipid droplets (LDs). The expression level of key genes (ACC, SCD-1, and FASN) involved in lipogenesis was increased, whereas the fundamental lipolysis gene, ATGL, was inhibited when SMPDL3B was knocked down. Overall, our findings suggest that SMPDL3B deficiency can effectively inhibit viral infection through the modulation of lipid metabolism.

Abnormality of anxious behaviors and functional connectivity between the amygdala and the frontal lobe in maternally deprived monkeys.

OBJECTIVE: Anxious behaviors often occur in individuals who have experienced early adversity. Anxious behaviors can bring many hazards, such as social withdrawal, eating disorders, negative self-efficacy, self-injurious thoughts and behaviors, anxiety disorders, and even depression. Abnormal behavior are is closely related to changes in corresponding circuit functions in the brain. This study investigated the relationship between brain circuits and anxious behaviors in maternal-deprived rhesus monkey animal model, which mimic early adversity in human. METHODS: Twenty-five rhesus monkeys (Macaca mulatta) were grouped by two different rearing conditions: 11 normal control and mother-reared (MR) monkeys and 14 maternally deprived and peer-reared (MD) monkeys. After obtaining images of the brain areas with significant differences in maternal separation and normal control macaque function, the relationship between functional junction intensity and stereotypical behaviors was determined by correlation analysis. RESULTS: The correlation analysis revealed that stereotypical behaviors were negatively correlated with the coupling between the left lateral amygdala subregion and the left inferior frontal gyrus in both MD and MR macaques. CONCLUSION: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The normalization of the regions involved in the functional connection might reverse the behavioral abnormality. It provides a solid foundation for effective intervention in human early adversity. SIGNIFICANCE STATEMENT: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The higher the amygdala-prefrontal connection strength, the less stereotyped behaviors exhibited by monkeys experiencing early adversity. Thus, in the future, changing the strength of the amygdala-prefrontal connection may reverse the behavioral abnormalities of individuals who experience early adversity. This study provides a solid foundation for effective intervention in humans' early adversity.

MiR-199a-5p enhances neuronal differentiation of neural stem cells and promotes neurogenesis by targeting Cav-1 after cerebral ischemia.

AIMS: MicroRNAs (miRs) are involved in endogenous neurogenesis, enhancing of which has been regarded as a potential therapeutic strategy for ischemic stroke treatment; however, whether miR-199a-5p mediates postischemic neurogenesis remains unclear. This study aims to investigate the proneurogenesis effects of miR-199a-5p and its possible mechanism after ischemic stroke. METHODS: Neural stem cells (NSCs) were transfected using Lipofectamine 3000 reagent, and the differentiation of NSCs was evaluated by immunofluorescence and Western blotting. Dual-luciferase reporter assay was performed to verify the target gene of miR-199a-5p. MiR-199a-5p agomir/antagomir were injected intracerebroventricularly. The sensorimotor functions were evaluated by neurobehavioral tests, infarct volume was measured by toluidine blue staining, neurogenesis was detected by immunofluorescence assay, and the protein levels of neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), caveolin-1 (Cav-1), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) were measured by Western blotting. RESULTS: MiR-199a-5p mimic enhanced neuronal differentiation and inhibited astrocyte differentiation of NSCs, while a miR-199a-5p inhibitor induced the opposite effects, which can be reversed by Cav-1 siRNA. Cav-1 was through the dual-luciferase reporter assay confirmed as a target gene of miR-199a-5p. miR-199a-5p agomir in rat stroke models manifested multiple benefits, such as improving neurological deficits, reducing infarct volume, promoting neurogenesis, inhibiting Cav-1, and increasing VEGF and BDNF, which was reversed by the miR-199a-5p antagomir. CONCLUSION: MiR-199a-5p may target and inhibit Cav-1 to enhance neurogenesis and thus promote functional recovery after cerebral ischemia. These findings indicate that miR-199a-5p is a promising target for the treatment of ischemic stroke.

IPAC integrates rewarding and environmental memory during the acquisition of morphine CPP.

The association between rewarding and drug-related memory is a leading factor for the formation of addiction, yet the neural circuits underlying the association remain unclear. Here, we showed that the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) integrated rewarding and environmental memory information by two different receiving projections from ventral tegmental area (VTA) and nucleus accumbens shell region (NAcSh) to mediate the acquisition of morphine conditioned place preference (CPP). A projection from the VTA GABAergic neurons (VTAGABA) to the IPAC lateral region GABAergic neurons (IPACLGABA) mediated the effect of morphine rewarding, whereas the pathway from NAcSh dopamine receptor 1-expressing neurons (NAcShD1) to the IPAC medial region GABAergic neurons (IPACMGABA) was involved in the acquisition of environmental memory. These findings demonstrated that the distinct IPAC circuits VTAGABA→IPACLGABA and NAcShD1R→IPACMGABA were attributable to the rewarding and environmental memory during the acquisition of morphine CPP, respectively, and provided the circuit-based potential targets for preventing and treating opioid addiction.

Management of regional citrate anticoagulation for continuous renal replacement therapy: guideline recommendations from Chinese emergency medical doctor consensus.

Continuous renal replacement therapy (CRRT) is widely used for treating critically-ill patients in the emergency department in China. Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT. Regional citrate anticoagulation (RCA) has been shown to potentially be safer and more effective and is now recommended as the preferred anticoagulant method for CRRT. However, there is still a lack of unified standards for RCA management in the world, and there are many problems in using this method in clinical practice. The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association (CMDA) organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues, including the advantages and disadvantages of RCA in CRRT anticoagulation, the principle of RCA, parameter settings for RCA, monitoring of RCA (mainly metabolic acid-base disorders), and special issues during RCA. Based on the latest available research evidence as well as the paneled experts' clinical experience, considering the generalizability, suitability, and potential resource utilization, while also balancing clinical advantages and disadvantages, a total of 16 guideline recommendations were formed from the experts' consensus.

Predictive Impact of Prognostic Nutritional Index in Patients with Cancer Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

A few previous studies have investigated the prognostic value of the prognostic nutritional index (PNI) in patients treated with immune checkpoint inhibitors (ICIs); however, the results are inconsistent. Therefore, this study aimed to clarify the prognostic significance of PNI. The PubMed, Embase, and Cochrane Library databases were searched. A meta-analysis of the impact of PNI on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and rate of adverse events (AEs) in patients treated with ICIs was performed. Twenty-three studies involving 2,386 patients were included. Low PNI was associated with significantly poor OS (hazard ratio [HR] = 2.26, 95% confidence interval [CI]: 1.81-2.82, P < .001) and short PFS (HR = 1.75, 95% CI: 1.54-1.99, P < .001). Patients with low PNI tended to have a low ORR (odds ratio [OR] = 0.47, 95% CI: 0.34-0.65, P < .001) and DCR (OR = 0.43, 95% CI: 0.34-0.56, P < .001). However, the subgroup analysis demonstrated no significant association between PNI and survival time in patients receiving a programmed death ligand-1 inhibitor. PNI was significantly associated with survival time and treatment efficacy in patients treated with ICIs.

Prognostic values of the prognostic nutritional index, geriatric nutritional risk index, and systemic inflammatory indexes in patients with stage IIB-III cervical cancer receiving radiotherapy.

Background: Growing evidence suggests that nutritional status and inflammation are associated with survival in various cancers. This study aimed to evaluate the prognostic value of the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and systemic inflammatory indexes (neutrophil/lymphocyte ratio [NLR], monocyte/lymphocyte ratio [MLR], and platelet/lymphocyte ratio [PLR]) in patients with stage IIB-III cervical cancer receiving radiotherapy. Results: The ideal cutoff values for the PNI, GNRI, NLR, MLR, and PLR were 48.3, 97.04, 2.8, 0.41, and 186.67, respectively. Low PNI and GNRI scores were associated with poor OS and PFS. High NLR, MLR, and PLR also predicted inferior 5-year OS and PFS rates in patients with stage IIB-III cervical cancer. Multivariate Cox regression analysis identified tumor size, histological type, stage, number of metastatic lymph nodes, PNI, GNRI, NLR, PLR, and MLR as significant prognostic factors for OS and PFS. Conclusions: The current findings suggest that the PNI, GNRI, NLR, PLR, and MLR are essential parameters for predicting prognosis in patients with stage IIB-III cervical cancer receiving radiotherapy.

The loss of Halloween gene function seriously affects the development and reproduction of Diaphorina citri (Hemiptera: Liviidae) and increases its susceptibility to pesticides.

The citrus industry has suffered severe losses as a result of Huanglongbing spread by Diaphorina citri. Controlling the population of D. citri is the key to preventing and controlling the spread of Huanglongbing. Ecdysteroids are key hormones that regulate insect development and reproduction. Therefore, the Halloween gene family involved in the ecdysone synthesis of D. citri is an ideal target for controlling the population growth of this insect. In this study, we successfully cloned four Halloween genes expressed during D. citri development. Silencing of one of the four genes resulted in a significant decrease in 20E titers in nymphs and significant decreases in the developmental, survival and emergence rates. Inhibiting Halloween gene expression in adults impeded the growth of the female ovary, diminished yolk formation, lowered vitellogenin transcription levels, and hence impaired female fecundity. This showed that Halloween genes were required for D. citri development and reproduction. DcCYP315A1 and DcCYP314A1 were highly expressed when D. citri was exposed to thiamethoxam and cypermethrin, and silencing these two genes made D. citri more sensitive to these two pesticides. Inhibition of DcCYP315A1 and DcCYP314A1 expression not only significantly delayed the development and reproduction of D. citri but also increased its susceptibility to pesticides. Therefore, these two genes are more suitable as potential target genes for controlling D. citri.

D-chiro-inositol increases antioxidant capacity and longevity of Caenorhabditis elegans via activating Nrf-2/SKN-1 and FOXO/DAF-16.

D-chiro-inositol (DCI) is an isomer of inositol, abundant in many foods, such as beans and buckwheat, with insulin-sensitizing, anti-inflammatory, and antioxidant effects. DCI has been used to relieve insulin resistance in diabetes and polycystic ovary syndrome in combination with inositol or D-pinitol. Here, we investigated the effect of DCI on aging and stress resistance in C. elegans. We found that DCI could prolong the lifespan of C. elegans by up to 29.6 %. DCI significantly delayed the onset of neurodegenerative diseases in models of C. elegans. DCI decreased the accumulation of Aß1-42, alpha-synuclein, and poly-glutamine, the pathological causes of Alzheimer's, Parkinson's, and Huntington's diseases, respectively. DCI significantly increased the stress resistances against pathogens, oxidants and heat shock. Moreover, D-chiro-inositol reduced the content of ROS and malondialdehyde by increasing the total antioxidant capacity and the activity of superoxide dismutase and catalase. Above effects of DCI requires the transcription factors FOXO/DAF-16 and Nrf-2/SKN-1. DCI also increased the expression of downstream genes regulated by FOXO/DAF-16 and Nrf-2/SKN-1. In conclusion, DCI enhanced the antioxidant capacity and healthy lifespan of C. elegans by activating DAF-16, SKN-1, and HSF-1. Our results showed that DCI could be a promising antiaging agent that is worth further research on the mechanism and health supplemental application of DCI.

Predicting neurosurgical referral outcomes in patients with chronic subdural hematomas using machine learning algorithms - A multi-center feasibility study.

Background: Chronic subdural hematoma (CSDH) incidence and referral rates to neurosurgery are increasing. Accurate and automated evidence-based referral decision-support tools that can triage referrals are required. Our objective was to explore the feasibility of machine learning (ML) algorithms in predicting the outcome of a CSDH referral made to neurosurgery and to examine their reliability on external validation. Methods: Multicenter retrospective case series conducted from 2015 to 2020, analyzing all CSDH patient referrals at two neurosurgical centers in the United Kingdom. 10 independent predictor variables were analyzed to predict the binary outcome of either accepting (for surgical treatment) or rejecting the CSDH referral with the aim of conservative management. 5 ML algorithms were developed and externally tested to determine the most reliable model for deployment. Results: 1500 referrals in the internal cohort were analyzed, with 70% being rejected referrals. On a holdout set of 450 patients, the artificial neural network demonstrated an accuracy of 96.222% (94.444-97.778), an area under the receiver operating curve (AUC) of 0.951 (0.927-0.973) and a brier score loss of 0.037 (0.022-0.056). On a 1713 external validation patient cohort, the model demonstrated an AUC of 0.896 (0.878-0.912) and an accuracy of 92.294% (90.952-93.520). This model is publicly deployed: https://medmlanalytics.com/neural-analysis-model/. Conclusion: ML models can accurately predict referral outcomes and can potentially be used in clinical practice as CSDH referral decision making support tools. The growing demand in healthcare, combined with increasing digitization of health records raises the opportunity for ML algorithms to be used for decision making in complex clinical scenarios.

Wumei Wan attenuates angiogenesis and inflammation by modulating RAGE signaling pathway in IBD: Network pharmacology analysis and experimental evidence.

BACKGROUND: Wumei Wan (WMW) has been used to address digestive disorder for centuries in traditional Chinese medicine. Previous studies have demonstrated its anti-colitis efficacy, but the underlying mechanism of its action remains to be further clarified. PURPOSE: To investigate the underlying mechanisms of WMW in the treatment of chronic ulcerative colitis (UC) through network pharmacology and experimental validation. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform were used to identify the ingredients and potential targets of WMW. The microarray gene data GSE75214 datasets from GEO database was used to define UC-associated targets. Cytoscape3.7.2 was employed to construct the protein-protein interaction (PPI) network and compounds-disease targets network. GO enrichment analysis and KEGG pathway analysis were performed by R software for functional annotation. UPLC-TOF-MS/MS method was used to quantitatively analyze the active ingredients of WMW. For experimental validation, three cycles of 2% dextran sulfate sodium salt (DSS) were used to construct chronic colitis model. The hub targets and signal pathway were detected by qPCR, ELISA, western blotting , immunohistochemical and immunofluorescence. RESULTS: Through network analysis, 104 active ingredients were obtained from WMW, and 47 of these ingredients had potential targets for UC. A total of 41 potential targets of WMW and 13 hub targets were identified. KEGG analysis showed that WMW involved in advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE) signaling pathway. Taxifolin, rutaecarpine, kaempferol, quercetin, and luteolin of WMW were the more highly predictive components related to the AGE-RAGE signaling pathway. In vivo validation, WMW improved DSS-induced colitis, reduced the expression of inflammatory cytokines and chemokines. Notably, it significantly decreased the mRNA expression of Spp1, Serpine1, Mmp2, Mmp9, Ptgs2, Nos2, Kdr and Icam1, which were associated with angiogenesis. In addition, we confirmed WMW inhibited RAGE expression and diminished DSS-induced epithelial barrier alterations CONCLUSION: Our results initially demonstrated the effective components and the strong anti-angiogenic activity of WMW in experimental chronic colitis. Sufficient evidence of the satisfactory anti-colitis action of WMW was verified in this study, suggesting its potential as a quite prospective agent for the therapy of UC.