Background and Objectives: Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus, yet its molecular mechanisms remain incompletely understood. This study aimed to identify key candidate genes and pathways associated with LN by integrated bioinformatics analysis and molecular validation. Methods: Gene expression data from the GSE32591 database, including glomerular and tubulointerstitial renal biopsy compartments from 32 patients with LN and 15 healthy controls, were analyzed to identify differentially expressed genes (DEGs). Functional enrichment analysis was performed using Metascape, while protein-protein interaction networks and hub genes were identified using STRING, Cytoscape, and CytoHubba. To further validate the bioinformatics results, the mRNA expression of hub genes was examined by quantitative real-time PCR in peripheral blood mononuclear cells (PBMCs) from 25 patients with LN and 25 healthy controls. Results: We identified 334 DEGs in the glomerular compartment and 125 DEGs in the tubulointerstitial compartment, with 66 overlapping DEGs between the two compartments. Enrichment analyses showed that these genes were mainly involved in interferon signaling, activation of the immune response, regulated exocytosis, phagocytosis, and lymphocyte activation. Network analyses highlighted TLR2/4 signaling and interleukin-4/interleukin-13 signaling as potentially relevant pathways. Ten hub genes were identified, among which eight genes (IFIT1, MX2, IFIT3, IFI6, IFIT2, OAS1, MX1, and ISG15) were significantly upregulated in PBMCs from patients with LN compared with healthy controls. Conclusion: Our findings indicate that interferon-related immune activation is a prominent molecular feature shared across renal compartments in LN. These results provide candidate genes and pathways for further validation as potential biomarkers and therapeutic targets in LN.
Health Technology Assessment (HTA) plays a central role in evidence-informed health policymaking by improving efficiency, equity, and transparency in allocating scarce healthcare resources. Despite advances in economic evaluation, clinical effectiveness assessment, and evidence synthesis, the institutionalization of HTA remains inconsistent, particularly in low- and middle-income countries. A major challenge lies in translating technical evidence into enforceable policy decisions. This Perspective argues that the limited institutionalization of HTA stems less from methodological shortcomings than from inadequate attention to Political Economy Analysis (PEA). HTA decisions are inherently political and distributive, often creating competing interests among stakeholders operating within complex institutional contexts. We propose integrating PEA into HTA processes to better understand actor incentives, governance arrangements, and political opportunities for reform. Three interrelated dimensions are highlighted: (i) actor and incentive mapping to facilitate coalition building, (ii) institutional analysis of formal and informal governance mechanisms, and (iii) identification of political feasibility windows for policy implementation. We also discuss emerging efforts to integrate governance and implementation science into HTA and outline future directions for embedding political economy perspectives. By linking technical evidence with political feasibility, PEA can strengthen HTA institutionalization and improve its translation into sustainable policy action.
Background and Objectives: Flumazenil is the standard antidote for benzodiazepine overdose but poses risks like seizures and a short half-life. Recent studies suggest caffeine may enhance recovery in benzodiazepine toxicity. This study evaluates caffeine's effect on consciousness recovery in benzodiazepinepoisoned patients and monitored its side effects. Methods: In a triple-blind, randomized controlled trial at Loghman Hakim Hospital, Tehran, patients with confirmed benzodiazepine poisoning were enrolled. Participants were randomized to receive either caffeine (100 mg every 8 hours) plus flumazenil (200 mcg/h intravenously) or flumazenil alone. The primary outcome was change in Glasgow Coma Scale (GCS) scores at 12, 24, 36, and 48 hours. Secondary outcomes included discharge rates, mortality, intubation, and hospitalization duration. Results: The study included 60 patients (31 females, 29 males) aged 16-98 years (mean 44). Baseline GCS scores were comparable between the intervention (9.7 +/- 2.5) and control (10.8 +/- 2.0) groups, with no significant differences in medical history or co-ingestion. The intervention group demonstrated significantly greater improvements in GCS at 12, 24, and 36 hours compared to controls (P < 0.05). By 48 hours, both groups achieved near-complete recovery. Earlier improvement in the intervention group was associated with shorter hospitalization (P = 0.040). Intubation and mortality rates did not differ significantly (P > 0.05). Conclusion: Caffeine combined with flumazenil accelerated recovery of consciousness and reduced hospitalization duration in benzodiazepine-poisoned patients. These findings suggest caffeine may be a useful adjunct in management of benzodiazepine overdose, particularly in resource-limited settings. Further studies are needed to optimize dosing and evaluate outcomes in severe cases.
Background and Objectives: Accurate early risk stratification in acute pancreatitis (AP) is essential to guide management and improve outcomes. Nucleated red blood cells (NRBCs) have been proposed as prognostic markers in critical illness; however, their role in AP remains unclear. In this study, we sought to investigate the success of nucleated red blood cells (NRBCs) in predicting disease severity and mortality in patients with AP. Methods: This single-center, retrospective study was conducted in AP patients admitted to the emergency department. NRBCs values and other laboratory data were recorded in the study form. Patients were divided into three groups according to disease severity (mild, moderate and severe) and two groups according to outcome (survivors and non-survivors). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of NRBCs for disease severity and in-hospital mortality. Results: Half of the 296 patients included in the study were male and the mean age was 55.6 +/- 17.9 years. NRBCs values were higher in severe cases tfhan in mild and moderate groups. In the Receiver operating characteristic (ROC) analysis performed to determine disease severity, the specificity, sensitivity and area under curve (AUC) values for NRBCs were 58,8%, 91.8%, and 0.755, respectively. NRBC values were higher in non-survivor patients compared with survivors. In the ROC analysis performed to detect non-survivors, the specificity sensitivity and AUC values for NRBCs were 63,6%, 90,9% and 0.770, respectively. The multivariable logistic regression analysis, NRBC was identified as an independent risk factor for both disease severity and mortality (P<0.001 for both analyses). Conclusion: In AP patients, high NRBCs levels may be successful in predicting both disease severity and mortality. However, more studies are needed for clinical use.
Background and Objectives: Myoclonus, caused by etomidate during general anesthesia induction, can lead to serious complications. Objectives: To determine how remimazolam pretreatment influences reduction in the incidence and severity of etomidate-related myoclonus. Methods: In this randomized controlled trial, 216 patients were assigned to 4 groups. Prior to etomidate induction, three groups received pretreatment with remimazolam at 0, 0.025, and 0.05 mg/kg doses (E, LRE, and HRE groups, respectively). The fourth group was anesthetized with 0.2 mg/kg remimazolam alone (R group). The primary outcome was myoclonus incidence and severity. Complications were also documented. The chi-square test/Fisher's exact test and two-way analysis of variance were used for the corresponding data. Results: Myoclonus frequency was lower in the LRE group (14/50, 28%), the HRE group (8/51, 16%), and the R group (0/51, 0%) than in the E group (28/52, 54%); myoclonus incidence showed a similar trend (P<0.001). Additionally, the HRE group performed better than the LRE group (P<0.001). Compared to the E group, the HRE, LRE, and R groups exhibited significantly lower incidence of intraoperative and postoperative complications (P=0.001); moreover, the HRE and LRE groups showed no significant difference in intraoperative and postoperative complications, while the R group had a lower incidence of complications than the HRE and LRE groups (P<0.001). Conclusion: Remimazolam pretreatment was feasible to prevent etomidate-associated myoclonus during gastroscopy. Remimazolam shows more efficacy at 0.05 mg/kg dose than at 0.025 mg/kg dose.
