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Medicine Jun 2024Our aim is to evaluate serum Raftlin levels as a biomarker for diagnosing and monitoring disease activity in patients with axial spondyloarthritis (axSpA) and Psoriatic... (Observational Study)
Observational Study
Our aim is to evaluate serum Raftlin levels as a biomarker for diagnosing and monitoring disease activity in patients with axial spondyloarthritis (axSpA) and Psoriatic arthritis (PsA). This trial included 40 axSpA patients, 40 PsA patients, and 40 healthy participants as the control group. Disease activity was assessed with Ankylosing Spondylitis Disease Activity Score for axSpA patients and The Disease Activity Index for Psoriatic Arthritis for PsA patients. The Spondyloarthritis Research Consortium of Canada index, health assessment questionnaire-disability index, and numeric rating scale were used to evaluate the enthesitis severity, disability, and pain status of all patients. Serum Raftlin levels were determined using the ELISA method. The 3 groups had no statistical differences regarding gender, age, weight, height, BMI, educational status, and exercise habits. The axSpA group had higher Raftlin levels than the PsA and control groups, and Raftlin levels were statistically significant in predicting the likelihood of axSpA. We found no statistically significant differences between the PsA and control groups. We found no statistically significant difference in Raftlin levels in HLA-B27 positive versus HLA-B27 negative patients in both axSpA and PsA groups. Our results also did not detect any correlation of Raftlin levels with Ankylosing Spondylitis Disease Activity Score, C-reactive protein, erythrocyte sedimentation rate, health assessment questionnaire-disability index, numeric rating scale, and Spondyloarthritis Research Consortium of Canada index in axSpA patients. Receiver operating characteristic analysis determined that Raftlin level ≥ 6.31 ng/mL discriminates axSpA from normal individuals with 92.5% sensitivity, 59% specificity, and an area under the curve of 0.738. Our results demonstrate that although serum Raftlin levels are elevated in axSpA patients, Raftlin cannot be used as an alone diagnostic marker for axSpA. Furthermore, it was not found to be related to the monitoring of disease activity, the level of pain, disability, or severity of enthesitis. This study is prospectively registered at www.clinicaltrials.gov (ID: NCT05771389).
Topics: Humans; Male; Female; Biomarkers; Arthritis, Psoriatic; Adult; Axial Spondyloarthritis; Severity of Illness Index; Middle Aged; Membrane Proteins; Case-Control Studies
PubMed: 38941376
DOI: 10.1097/MD.0000000000038770 -
Medicine Jun 2024The mortality rate related to variceal bleeding is high in patients with liver cirrhosis. Early detection and treatment of varices can reduce the risk of hemorrhage and...
The mortality rate related to variceal bleeding is high in patients with liver cirrhosis. Early detection and treatment of varices can reduce the risk of hemorrhage and thus decrease the mortality rate related to variceal bleeding. The study comprised 81 cirrhotic patients in training set, who were categorized into 2 groups: the patients with esophageal varices (EVs group) and the patients without esophageal varices (non-EVs group). The disparity in Cystatin C/albumin ratio (CAR) was assessed between these 2 groups. Subsequently, a regression model was constructed by generating a receiver operating characteristic (ROC) curve to calculate the area under the curve (AUC). Then an external validation was performed in 25 patients. Among patients with cirrhosis in training set, a statistically significant difference in CAR was observed between the EVs group and non-EVs group (P < .05). At the CAR cutoff value of 2.79*10-5, the AUC for diagnosing EVs were 0.666. Further, a multivariate logistic regression model was constructed, after adjusting the model, the AUC for EVs diagnosis were 0.855. And the external validation showed that the model could not be considered as a poor fit. CAR exhibits potential as an early detection marker for EVs in liver cirrhosis, and the regression model incorporating CAR demonstrates a strong capability for early EVs diagnosis.
Topics: Humans; Esophageal and Gastric Varices; Liver Cirrhosis; Cystatin C; Male; Female; Middle Aged; Early Diagnosis; Biomarkers; ROC Curve; Aged; Serum Albumin; Adult; Retrospective Studies; Area Under Curve
PubMed: 38941375
DOI: 10.1097/MD.0000000000038481 -
Medicine Jun 2024As chronic autoimmune inflammatory diseases, rheumatoid arthritis (RA) and Crohn disease (CD) are closely associated and display a significant positive correlation....
As chronic autoimmune inflammatory diseases, rheumatoid arthritis (RA) and Crohn disease (CD) are closely associated and display a significant positive correlation. However, the underlying mechanisms and disease markers responsible for their cooccurrence remain unknown and have not been systematically studied. Therefore, this study aimed to identify key molecules and pathways commonly involved in both RA and CD through bioinformatic analysis of public sequencing databases. Datasets for RA and CD were downloaded from the GEO database. Overlapping genes were identified using weighted gene co-expression network analysis and differential analysis crossover, and enrichment analysis was conducted for these genes. Protein-protein interaction networks were then constructed using these overlapping genes to identify hub genes. Expression validation and receiver operating characteristic curve validation were performed for these hub genes using different datasets. Additionally, the immune cell correlation, single-cell expression cluster, and the immune cell expression cluster of the core gene were analyzed. Furthermore, upstream shared microRNAs (miRNA) were predicted and a miRNA-gene network was constructed. Finally, drug candidates were analyzed and predicted. These core genes were found to be positively correlated with multiple immune cells that are infiltrated by the disease. Analysis of gene expression clusters revealed that these genes were mostly associated with inflammatory and immune responses. The miRNA-genes network analysis suggested that hsa-miR-31-5p may play an important role in the common mechanism of RA and CD. Finally, tamibarotene, retinoic acid, and benzo[a]pyrene were identified as potential treatment options for patients with both RA and CD. This bioinformatics study has identified ITGB2, LCP2, and PLEK as key diagnostic genes in patients with both RA and CD. The study has further confirmed that inflammation and immune response play a central role in the development of both RA and CD. Interestingly, the study has highlighted hsa-miR-31-5p as a potential key player in the common mechanism of both diseases, representing a new direction in research and a potential therapeutic target. These shared genes, potential mechanisms, and regulatory networks offer new opportunities for further research and may provide hope for future treatment of patients with both RA and CD.
Topics: Humans; Crohn Disease; Arthritis, Rheumatoid; Computational Biology; MicroRNAs; Protein Interaction Maps; Gene Regulatory Networks; Biomarkers; Gene Expression Profiling
PubMed: 38941374
DOI: 10.1097/MD.0000000000038690 -
Medicine Jun 2024Alterations in signaling pathways and modulation of cell metabolism are associated with the pathogenesis of cancers, including hepatocellular carcinoma (HCC). Small... (Observational Study)
Observational Study
Alterations in signaling pathways and modulation of cell metabolism are associated with the pathogenesis of cancers, including hepatocellular carcinoma (HCC). Small ubiquitin-like modifier (SUMO) proteins and NF-κB family play major roles in various cellular processes. The current study aims to determine the expression profile of SUMO and NF-κB genes in HCC tumors and investigate their association with the clinical outcome of HCC. The expression of 5 genes - SUMO1, SUMO2, SUMO3, NF-κB p65, and NF-κB p50 - was quantified in tumor and adjacent non-tumor tissues of 58 HBV-related HCC patients by real-time quantitative PCR and was analyzed for the possible association with clinical parameters of HCC. The expression of SUMO2 was significantly higher in HCC tumor tissues compared to the adjacent non-tumor tissues (P = .01), while no significant difference in SUMO1, SUMO3, NF-κB p65, and NF-κB p50 expression was observed between HCC tumor and non-tumor tissues (P > .05). In HCC tissues, a strong correlation was observed between the expression of SUMO2 and NF-κB p50, between SUMO3 and NF-κB p50, between SUMO3 and NF-κB p65 (Spearman rho = 0.83; 0.82; 0.772 respectively; P < .001). The expression of SUMO1, SUMO2, SUMO3, NF-κB p65, and NF-κB p50 was decreased in grade 3 compared to grades 1 and 2 in HCC tumors according to the World Health Organization grades system. Our results highlighted that the SUMO2 gene is upregulated in tumor tissues of patients with HCC, and is related to the development of HCC, thus it may be associated with the pathogenesis of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; Middle Aged; Small Ubiquitin-Related Modifier Proteins; SUMO-1 Protein; NF-kappa B; Adult; Transcription Factor RelA; Hepatitis B virus; NF-kappa B p50 Subunit; Aged; Gene Expression Regulation, Neoplastic; Ubiquitins; Hepatitis B
PubMed: 38941371
DOI: 10.1097/MD.0000000000038737 -
Medicine Jun 2024Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast surgery patients.
METHODS
In this study, breast cancer patients undergoing modified radical mastectomy were randomized into 3 groups for anesthesia (30 patients in each group): standard general (group C), Erector Spinae Plane Block (ESPB) with ropivacaine (group R), and ESPB with ropivacaine plus hydromorphone (group HR). Diagnosis: Breast cancer patients. Postsurgery, pain levels, IL-6, anesthetic doses, additional analgesia needs, and recovery milestones were compared to evaluate the efficacy of the ESPB enhancements.
RESULTS
The 3 groups were not significantly different in baseline characteristics, operation time, number of cases with postoperative nausea, and serum IL-6 concentrations at T1 (the time of being returned to the ward after surgery). At T2 (at 6:00 in the next morning after surgery), the serum IL-6 concentration in group HR was significantly lower than that in groups R and C (P < .05); the intraoperative doses of remifentanil, sufentanil, and propofol were significantly lower in groups HR and R than those in group C (P < .05); Groups HR and R had significantly lower visual analog scale scores at T3 (4 hours postoperatively), T4 (12 hours postoperatively), and T5 (24 hours postoperatively) than those in group C (P < .05); the proportions of patients receiving postoperative remedial analgesia were significantly lower in groups HR and R than in group C (P < .05); groups HR and R had significantly lower proportions of patients with postoperative nausea than group C (P < .05); the time to the first anal exhaust and the time to the first ambulation after surgery were significantly shorter in groups HR and R than those in group C (P < .05).
CONCLUSION
Hydromorphone combined with ropivacaine for ESPB achieved a greater postoperative analgesic effect for patients receiving MRM under general anesthesia. The combined analgesia caused fewer adverse reactions and inhibited the expression level of the inflammatory factor IL-6 more effectively, thereby facilitating postoperative recovery. ESPB using hydromorphone with ropivacaine improved pain control post-MRM, reduced adverse effects, and more effectively suppressed IL-6, enhancing recovery.
Topics: Humans; Ropivacaine; Female; Hydromorphone; Middle Aged; Nerve Block; Pain, Postoperative; Prospective Studies; Anesthetics, Local; Breast Neoplasms; Mastectomy, Modified Radical; Analgesics, Opioid; Adult; Interleukin-6; Paraspinal Muscles; Ultrasonography, Interventional; Drug Therapy, Combination; Pain Measurement
PubMed: 38941366
DOI: 10.1097/MD.0000000000038758 -
Medicine Jun 2024NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) is a novel lipid parameter. However, the association between NHHR and sleep...
NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) is a novel lipid parameter. However, the association between NHHR and sleep disorders remains unknown.; A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2016. The association between NHHR and sleep disorders was explored using weighted multivariate logistic regression and generalized summation models. Subgroup analyses were employed to verify the robustness of this association. The prevalence of sleep disorders was 25.83% in a total of 22,221 participants. Compared to the lowest quartile of NHHR, participants in the top quartile had a 14% higher odds of sleep disorders prevalence in fully adjusted model (OR: 1.14, 95% CI: 1.06-1.23). After subgroup analyses and interaction tests, sex, race, marital status, education level, body mass index (BMI), person income ratio (PIR), alcohol consumption, smoking status, hypertension, and diabetes mellitus were not significantly associated with this positive association (P for interaction > 0.05). The NHHR is positively associated with sleep disorders in US adults. The management and monitoring of NHHR may have a potential role in improving sleep disorders.
Topics: Humans; Male; Female; Nutrition Surveys; United States; Cross-Sectional Studies; Sleep Wake Disorders; Middle Aged; Adult; Cholesterol, HDL; Prevalence; Risk Factors; Aged
PubMed: 38941362
DOI: 10.1097/MD.0000000000038748 -
PLoS Pathogens Jun 2024Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to...
Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73+CD80+ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.
PubMed: 38941356
DOI: 10.1371/journal.ppat.1012334 -
PloS One 2024Prenatal alcohol exposure (PAE) causes cognitive impairment and a distinctive craniofacial dysmorphology, due in part to apoptotic losses of the pluripotent cranial...
Prenatal alcohol exposure (PAE) causes cognitive impairment and a distinctive craniofacial dysmorphology, due in part to apoptotic losses of the pluripotent cranial neural crest cells (CNCs) that form facial bones and cartilage. We previously reported that PAE rapidly represses expression of >70 ribosomal proteins (padj = 10-E47). Ribosome dysbiogenesis causes nucleolar stress and activates p53-MDM2-mediated apoptosis. Using primary avian CNCs and the murine CNC line O9-1, we tested whether nucleolar stress and p53-MDM2 signaling mediates this apoptosis. We further tested whether haploinsufficiency in genes that govern ribosome biogenesis, using a blocking morpholino approach, synergizes with alcohol to worsen craniofacial outcomes in a zebrafish model. In both avian and murine CNCs, pharmacologically relevant alcohol exposure (20mM, 2hr) causes the dissolution of nucleolar structures and the loss of rRNA synthesis; this nucleolar stress persisted for 18-24hr. This was followed by reduced proliferation, stabilization of nuclear p53, and apoptosis that was prevented by overexpression of MDM2 or dominant-negative p53. In zebrafish embryos, low-dose alcohol or morpholinos directed against ribosomal proteins Rpl5a, Rpl11, and Rps3a, the Tcof homolog Nolc1, or mdm2 separately caused modest craniofacial malformations, whereas these blocking morpholinos synergized with low-dose alcohol to reduce and even eliminate facial elements. Similar results were obtained using a small molecule inhibitor of RNA Polymerase 1, CX5461, whereas p53-blocking morpholinos normalized craniofacial outcomes under high-dose alcohol. Transcriptome analysis affirmed that alcohol suppressed the expression of >150 genes essential for ribosome biogenesis. We conclude that alcohol causes the apoptosis of CNCs, at least in part, by suppressing ribosome biogenesis and invoking a nucleolar stress that initiates their p53-MDM2 mediated apoptosis. We further note that the facial deficits that typify PAE and some ribosomopathies share features including reduced philtrum, upper lip, and epicanthal distance, suggesting the facial deficits of PAE represent, in part, a ribosomopathy.
Topics: Animals; Neural Crest; Zebrafish; Ribosomes; Ethanol; Tumor Suppressor Protein p53; Apoptosis; Mice; Proto-Oncogene Proteins c-mdm2; Cell Nucleolus; Ribosomal Proteins; Skull; Zebrafish Proteins
PubMed: 38941348
DOI: 10.1371/journal.pone.0304557 -
PloS One 2024A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel...
A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel therapeutic options, few antibiotics targeting MDR have been approved by the Food and Drug Administration (FDA). Lactic acid bacteria have emerged as a promising therapeutic alternative due to their demonstrated ability to combat MDR pathogens in vitro. Our previous co-culture studies showed Lacticaseibacillus rhamnosus CRL 2244 as having a potent killing effect against carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Here we report that cell-free conditioned media (CFCM) samples obtained from Lcb. rhamnosus CRL 2244 cultures incubated at different times display antimicrobial activity against 43 different pathogens, including CRAB, methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase Klebsiella pneumoniae (KPC)-positive strains. Furthermore, transwell and ultrafiltration analyses together with physical and chemical/biochemical tests showed that Lcb. rhamnosus CRL 2244 secretes a <3 kDa metabolite(s) whose antimicrobial activity is not significantly impaired by mild changes in pH, temperature and various enzymatic treatments. Furthermore, sensitivity and time-kill assays showed that the bactericidal activity of the Lcb. rhamnosus CRL 2244 metabolite(s) enhances the activity of some current FDA approved antibiotics. We hypothesize that this observation could be due to the effects of Lcb. rhamnosus CRL 2244 metabolite(s) on cell morphology and the enhanced transcriptional expression of genes coding for the phenylacetate (PAA) and histidine catabolic Hut pathways, metal acquisition and biofilm formation, all of which are associated with bacterial virulence. Interestingly, the extracellular presence of Lcb. rhamnosus CRL 2244 induced the transcription of the gene coding for the CidA/LgrA protein, which is involved in programmed cell death in some bacteria. Overall, the findings presented in this report underscore the promising potential of the compound(s) released by Lcb. rhamnosus CRL2244 as an alternative and/or complementary option to treat infections caused by A. baumannii as well as other MDR bacterial pathogens.
Topics: Lacticaseibacillus rhamnosus; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Acinetobacter baumannii; Drug Synergism; Methicillin-Resistant Staphylococcus aureus; Culture Media, Conditioned; Bacterial Proteins
PubMed: 38941324
DOI: 10.1371/journal.pone.0306273 -
PloS One 2024We aimed to determine the rate and impact of post-pericardiotomy syndrome after native valve-sparing aortic valve surgery and the perioperative factors associated with...
BACKGROUND
We aimed to determine the rate and impact of post-pericardiotomy syndrome after native valve-sparing aortic valve surgery and the perioperative factors associated with its occurrence.
METHODS
All consecutive patients who underwent native valve-sparing aortic valve surgery (i.e., repair ± ascending aorta replacement, valve-sparing root replacement, Ross procedure ± ascending aorta replacement) at our institution between January 2021 and August 2023 served as our study population. Post-pericardiotomy syndrome was diagnosed if patients showed at least two of the following diagnostic criteria: evidence of (I) new/worsening pericardial effusion, or (II) new/worsening pleural effusions, (III) pleuritic chest pain, (IV) fever or (V) elevated inflammatory markers without alternative causes. A logistic regression model was calculated.
RESULTS
During the study period, 91 patients underwent native valve-sparing aortic valve surgery. A total of 21 patients (23%) developed post-pericardiotomy syndrome early after surgery (PPS group). The remaining 70 patients (77%) showed no signs of post-pericardiotomy syndrome (non-PPS group). Multivariate logistic regression revealed blood type O (OR: 3.15, 95% CI: 1.06-9.41, p = 0.040), valve-sparing root replacement (OR: 3.12, 95% CI: 1.01-9.59, p = 0.048) and peak C-reactive protein >15 mg/dl within 48 hours postoperatively (OR: 4.27, 95% CI: 1.05-17.29, p = 0.042) as independent risk factors. 73% (8/11) of patients displaying all three risk factors, 60% (9/15) of patients with blood type O and valve-sparing root replacement, 52% (11/21) of patients with blood type O and early postoperative peak C-reactive protein >15 mg/dl and 45% (13/29) of patients with early postoperative peak C-reactive protein >15 mg/dl and valve-sparing root replacement developed post-pericardiotomy syndrome.
CONCLUSION
In summary, blood type O, valve-sparing root replacement and peak C-reactive protein >15 mg/dl within 48 hours postoperatively are significantly associated with post-pericardiotomy syndrome after native valve-sparing aortic valve surgery. Particularly, the presence of all three risk factors is linked to a particularly high risk of post-pericardiotomy syndrome.
Topics: Humans; Male; Female; Middle Aged; Aortic Valve; Postpericardiotomy Syndrome; Aged; Risk Factors; Postoperative Complications; Retrospective Studies; Pericardiectomy; Adult
PubMed: 38941316
DOI: 10.1371/journal.pone.0306306