Journal of Investigative Medicine最新文献

Galectin-9 (Gal-9) has a significant regulatory function in autoimmune disorders, including systemic lupus erythematosus (SLE). The objective of this study was to assess the blood levels of Galectin-9 in patients with SLE and investigate the correlation between the protein and disease activity. The study employed a case-control design involving 75 participants, aged between 25 and 55 years, representing both sexes, all of whom had been diagnosed with SLE and were either in a quiescent or active phase of the disease. Three equal groups of participants were created. It was shown that Galectin-9 has 88% sensitivity and 80% specificity, with an area under the curve (AUC) of 0.901. With a computed positive predictive value of 81% and a negative predictive value of 87%, the total accuracy was 84%. In addition, a strong positive connection (R = 0.606) was found between anti-double strand DNA and Gal-9 levels, urea (R = 0.482), creatinine (R = 0.530), proteinuria (R = 0.488), albumin-to-creatinine ratio (R = 0.7), and SLEDAI (R = 0.815) and there is negative correlation with hemoglobin (R = -0.772), white blood cells (R = -0.849), platelets (R = -0.481), and complement 3 (R = -0.578). Compared to healthy persons, patients with SLE had considerably higher serum concentrations of Gal-9. Patients without active illness did not have elevated levels of Gal-9; those with active SLE did. Moreover, Gal-9 showed a robust association with the activity of SLE illness, indicating a possible involvement in the onset of SLE.

Graves' disease (GD) is an autoimmune thyroid disorder characterized by excessive thyroid hormone production driven by thyroid-stimulating hormone (TSH) receptor antibodies (TRAb). This study aimed to investigate the relationship between serum spexin (SPX) levels, TRAb levels, thyroid ultrasound findings, and metabolic parameters in GD patients while evaluating SPX as a potential biomarker for autoimmune inflammation. A prospective, single-center study included 45 GD patients and 45 healthy controls. Serum TSH, free T3, free T4, anti-thyroglobulin, antithyroid peroxidase, TRAb, and SPX levels were measured. Thyroid ultrasonography classified patients into mild, moderate, and high heterogeneity groups. SPX levels were significantly higher in GD patients compared to controls (p < 0.001) and showed a strong positive correlation with TRAb levels (r = 0.579, p < 0.001) and thyroid heterogeneity (p < 0.001). Newly diagnosed patients (<6 months) exhibited the highest SPX levels, which decreased with prolonged disease duration. Receiver operating characteristic analysis identified a cutoff value of 105 pg/mL for SPX, yielding 60% sensitivity and 91.1% specificity (area under the curve: 0.765, p < 0.001). SPX levels were also inversely correlated with disease duration and positively associated with inflammatory markers, suggesting its utility in monitoring disease activity and progression. These findings highlight SPX as a novel biomarker for assessing disease severity and autoimmune inflammation in GD. Incorporating SPX measurements into clinical practice may aid in early diagnosis, disease stratification, and therapeutic monitoring, ultimately improving personalized care for GD patients.

Liver biopsy remains the diagnostic gold standard for assessing liver fibrosis severity; however, its cost and invasiveness highlight the need for accurate, noninvasive alternatives. This study evaluates the performance of FibroPredict, a novel algorithm, for detecting advanced liver fibrosis in high-risk populations. It compares its accuracy to transient elastography (TE), the current noninvasive reference standard. A retrospective cohort study of 316 high-risk individuals used electronic health record (EHR) data and routine laboratory results to calculate FibroPredict, APRI (Aspartate Aminotransferase-to-Platelet Ratio Index), and FIB-4 scores, which were then compared to liver stiffness measurements (LSM) obtained through TE. FibroPredict demonstrated a sensitivity of 96.8% and a negative predictive value (NPV) of 90.9% at a cutoff score of ≥135 for detecting advanced fibrosis (LSM ≥ 8 kPa), outperforming FIB-4 in sensitivity and the ability to rule out advanced fibrosis. APRI, at a cutoff of 1.5, showed high specificity (98.41%) but low sensitivity (6.32%), making it more suitable for confirming rather than excluding advanced fibrosis. However, FibroPredict's specificity was low (21.0%), resulting in higher false-positive rates. FIB-4, with a cutoff of ≥2.67, showed lower sensitivity but better specificity (46.8%). FibroPredict's excellent sensitivity and high NPV make it a promising tool for ruling out advanced fibrosis, particularly in resource-limited settings. However, its low specificity underscores the need for confirmatory tests, such as TE, or combining it with APRI to enhance diagnostic accuracy.

The global impact of COVID-19, caused by SARS-CoV-2, has extended beyond acute infection, with post-acute COVID-19 syndrome (PACS) affecting an estimated 10% of recovered individuals. PACS manifests a range of debilitating symptoms, including fatigue, cognitive impairment, and gastrointestinal issues. While vaccination has proven effective in mitigating severe COVID-19 outcomes, the role of booster doses in preventing PACS remains unclear. This study aimed to evaluate whether COVID-19 booster vaccinations reduce the incidence and severity of PACS in individuals with prior SARS-CoV-2 infection. A systematic review and meta-analysis were conducted, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Databases PubMed, Embase, and Cochrane were searched for peer-reviewed studies published in English from January 2020 to August 2023. Inclusion criteria encompassed randomized controlled trials, prospective cohort studies, and case-control studies comparing PACS prevalence between booster recipients and non-recipients. The risk of bias was assessed using the Joanna Briggs Institute appraisal tool. Data synthesis included pooled prevalence estimates and narrative analyses. Of 849 identified studies, 22 met inclusion criteria, with 12 providing complete data for meta-analysis. Among 38,718 participants, a trend toward lower PACS prevalence was observed in booster recipients (RR: 0.66; 95% CI: 0.41-1.09), though heterogeneity (I² = 98%) limited statistical significance. Risk of bias analysis classified most studies as low or moderate risk, with two high-risk studies reporting higher PACS rates in boosted individuals. This study suggests a potential protective effect of booster vaccinations against PACS, though findings were not statistically significant. Further research with larger, standardized cohorts is essential to validate these observations and guide vaccination strategies.Prospero Record Number: CRD42023461326.

Drug resistance restrains the efficacy of platinum-based chemotherapy against esophageal squamous cell carcinoma (ESCC). Long noncoding RNAs (lncRNAs) play crucial roles in various cancers. In this study, we conducted bioinformatical analysis to search for key lncRNAs involved in ESCC progression. Experimental validations focused on a candidate lncRNA, HMGA2-AS1. The roles of the lncRNA HMGA2-AS1 in ESCC growth and cisplatin resistance were explored. The clinical significance of HMGA2-AS1 in ESCC was also determined. Our data demonstrated that HMGA2-AS1 was significantly upregulated in ESCC relative to adjacent normal tissues and correlated with tumor size (p = 0.0035) and tumor stage (p = 0.0001). Knockdown of HMGA2-AS1 suppressed the proliferation and colony formation and increased cisplatin sensitivity in ESCC cells. In vivo tumorigenic studies showed that depletion of HMGA2-AS1 impaired tumorigenesis of ESCC cells. Enforced expression of HMGA2-AS1 promoted ESCC proliferation and cisplatin resistance. HMGA2-AS1 interacted with HMGA2 protein in the nucleus of ESCC cells, promoting HMGA2-dependent transactivation of Snail2. Silencing of HMGA2 abrogated HMGA2-AS1-induced proliferation and cisplatin resistance in ESCC cells, which were rescued by overexpression of Snail2. In conclusion, our results highlight the importance of HMGA2-AS1 in ESCC growth and cisplatin resistance. HMGA2-AS1-induced aggressive phenotype in ESCC depends on the interaction with HMGA2. HMGA2-AS1 may serve as a potential therapeutic target for ESCC.

This study aims to delineate the underlying mechanism by which propofol triggers ferroptosis in lung cancer cells through the inhibition of the circZFR/IGF2BP2/GPX4 axis. The expression levels of circZFR, insulin-like growth factor 2 binding protein 2 (IGF2BP2), and glutathione peroxidase 4 (GPX4) in lung cancer cells were assessed using quantitative real-time polymerase chain reaction and Western blot analysis. Cell viability was evaluated with the cell counting kit-8 assay, and ferroptosis-related indicators were measured using appropriate kits. The interactions between circZFR and IGF2BP2, as well as between GPX4 and IGF2BP2, were investigated through RNA pull-down and RNA immunoprecipitation assays, and their effects on ferroptosis were analyzed using rescue assays. In addition, xenograft assays in nude mice were conducted to evaluate the impact of propofol on tumor growth and ferroptosis in vivo. Propofol treatment induced cell ferroptosis, as evidenced by decreased cell viability and elevated levels of malondialdehyde (MDA), Fe²⁺, and lipid reactive oxygen species in H1299 and SPC-A-1 cells. In addition, propofol reduced the expression of circZFR and GPX4 in lung cancer cells. Notably, the overexpression of circZFR inhibited propofol-induced ferroptosis in these cells. CircZFR interacts with IGF2BP2 to regulate the stability of GPX4 mRNA and its protein expression. Furthermore, circZFR inhibited GPX4-mediated ferroptosis by enhancing IGF2BP2 expression in both H1299 and SPC-A-1 cell lines. Moreover, propofol inhibited tumor growth in nude mice, downregulated the expression of circZFR, IGF2BP2, and GPX4, and increased MDA and Fe²⁺ levels in tumor tissues. Propofol downregulates circZFR to inhibit the expression of GPX4 by interacting with IGF2BP2, thereby triggering ferroptosis in lung cancer cells.

The expression of nicotinamide-phosphoribosyl transferase (NAMPT) was demonstrated to increase in various dysplastic and malignant conditions, usually consistent with the severity of the disease. This study was conducted to assess the utility of extracellular NAMPT (eNAMPT) in the management of cervical dysplasia in human papillomavirus (HPV) infected women. Circulating eNAMPT concentrations in high-risk HPV-infected women who were diagnosed with high-grade squamous intraepithelial lesion (HSIL) or invasive cancer (cervical intraepithelial neoplasia 2+ (CIN2+) lesions) and who were revealed to have no cervical dysplasia or low-grade squamous intraepithelial lesion (LSIL) were evaluated and compared. One hundred fifty nine high-risk HPV-infected patients for cervical biopsies under colposcopy guidance between February 2022 and February 2023 were included in this case-control study. Study group composed of consecutively enrolled 84 women with histological diagnosis of HSIL or cervical cancer (CIN2+ lesions) and control group composed of consecutively enrolled 75 women with LSIL or normal cervical biopsies. Circulating eNAMPT concentrations of cases with CIN2+ lesions and cases with LSIL or normal cervical biopsies were compared. No significant difference was found between median peripheral venous blood eNAMPT concentration of cases with histologic diagnosis of CIN2+ lesions and cases with LSIL or normal cervical biopsies (9.4 ng/mL (0.19-192) vs 8.9 ng/mL (0.19-176.9); p = 0.07, respectively). Multivariate linear regression analysis revealed no independent predictor of circulating eNAMPT concentrations among possible predictor variables. In conclusion, circulating eNAMPT concentrations of cases with CIN2+ lesions and cases with LSIL or normal cervical biopsies were found to be similar. Further research that evaluates cervical fluid eNAMPT concentrations might define novel noninvasive tools in cervical dysplasia management.

Greater than 25% of the American population has a disability. The demand for disability-informed physicians underscores the need to better prepare physicians to care for patients with disabilities. This study presents findings from three Qualtrics survey studies that investigated (1) medical students' exposure to patients with disabilities while on clinical rotations at Western University of Health Sciences, (2) students' perceived preparedness to care for patients with disabilities nationwide, and (3) the effectiveness of Special Olympics online modules to teach students about caring for patients with disabilities. Descriptive analysis from these studies together indicated that medical students did not feel prepared to care for patients with disabilities. To remedy this, Special Olympics online modules for healthcare professionals were found to effectively enhance student physician training. These findings highlight a critical need for improved medical training to prepare the next generation of physicians to care for patients with disabilities, while outlining a possible educational tool that could be incorporated into medical school curriculum.

Cirrhosis, an advanced stage of liver disease, induces cirrhosis-associated immune dysfunction syndrome (CAIDS), characterized by both innate and adaptive immune dysfunction. Inflammation triggered by factors such as alcohol, viruses, toxins, and cholesterol induces metabolic reprogramming of both innate and adaptive immune cells. Our study specifically sought to investigate the compromised adaptive immune response in cirrhosis by focusing on assessing T-cell exhaustion and activation markers on helper and cytotoxic T cells. A prospective observational study involving 19 liver cirrhosis patients and 36 healthy controls was conducted. The hepatic decompensation degree was assessed using various parameters, including serum bilirubin, albumin, international normalized ratio, ascites, and hepatic encephalopathy. T cell activation (CD38, CD44, CD69, HLADR) and exhaustion markers (CTLA-4, PD-1, TIM-3, LAG-3) were assessed on helper and cytotoxic T cells by flow cytometry. Cirrhosis patients showed reduced T cells with no alteration in the CD4:CD8 T cell ratio. Among activation markers, HLADR showed increased expression on CD8+ T cells (p = 0.031). Regarding exhaustion markers, LAG-3 and TIM-3 exhibited increased expression in cirrhotic patients compared to controls in both CD4 and CD8 T cells (p = 0.004, p = 0.016, p = 0.001, p = 0.004, respectively). Neither cirrhotic nor healthy controls showed CTLA expression. PD-1 did not differ significantly between the two groups. Co-expression of PD-1/TIM-3 on CD8+ T cells was notably higher in cirrhotic patients (p < 0.002). The observation of impaired adaptive immunity with notable T-cell exhaustion and activation in cirrhosis underscores the potential relevance of immunotherapy.

Mortality prediction in the intensive care unit (ICU) is essential in patient management. Emerging methods such as machine learning (ML) can be employed to predict ICU patients' mortality. Patients receiving treatment in the ICU of the internal medicine department were subjected to ML analysis upon admission, considering demographic, laboratory, and medical scores. Data from 787 internal medicine ICU patients were analyzed, with only a subset (220) included in the study for the 30-day mortality prediction model. The performance of boosting and Logistic Regression models in mortality prediction was compared. Categorical boosting (CatBoost) achieved the highest area under the curve (AUC) of 0.90, while extreme gradient boosting reached a maximum AUC of 0.85, and Logistic Regression attained the highest AUC of 0.83. Incorporating Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, and Sequential Organ Failure Assessment scores with clinical and laboratory values, CatBoost demonstrated the strongest predictive performance with high sensitivity and specificity. In the ICU of the internal medicine department, it was concluded that the ML models successfully predict mortality.