Type 2 diabetes mellitus (T2DM) is a global health crisis, with cardiovascular disease (CVD) accounting for 75% of mortality in this population. Despite advances in managing traditional risk factors, such as low-density lipoprotein cholesterol (LDL) cholesterol reduction (IMPROVE-IT, FOURIER), antithrombotic therapies (PEGASUS, COMPASS), and triglyceride-lowering agents (REDUCE-IT), a substantial residual cardiovascular risk persists, driven in part by chronic low-grade systemic inflammation. Chronic low-grade inflammation is a central driver of cardiovascular-kidney-metabolic (CKM) syndrome in T2DM, perpetuating residual cardiovascular risk despite optimal management of traditional risk factors. This narrative review synthesizes evidence on how inflammation accelerates coronary heart disease (CHD), heart failure (HF), stroke, diabetic kidney disease (DKD), and peripheral artery disease (PAD). We evaluate the anti-inflammatory mechanisms of current therapies such as statins, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists, as well as emerging agents like colchicine and interleukin (IL)-1β/IL-6 inhibitors, emphasizing their differential efficacy across CKM traits. By integrating pathophysiological insights with clinical trial data, we propose biomarker-guided strategies to target inflammation as a modifiable risk factor, offering a roadmap to bridge the gap in diabetes-related cardiovascular care.

Cancer remains a major cause of mortality worldwide, driving ongoing innovation in therapeutic strategies. Immunotherapy has transformed cancer care by leveraging the immune system to target tumors, but its effectiveness is limited by tumor heterogeneity, immune resistance, and unpredictable toxicities. Moreover, the absence of robust biomarkers to predict therapeutic response and manage adverse effects remains a significant challenge. Recent advances in biomarker discovery, including liquid biopsy technologies and gut microbiota profiling, are enhancing the precision of immunotherapy and enabling more personalized cancer management. Here, we present a Comprehensive Oncological Biomarker Framework that integrates genetic and molecular testing, imaging, histopathology, multi-omics, and liquid biopsy to generate a molecular fingerprint for each patient. This holistic approach supports individualized diagnosis, prognosis, treatment selection, and response monitoring. Incorporating emerging biomarkers, such as microbiome signatures, further refines patient stratification, guiding the optimization of therapy. By uniting molecular insights with clinical and social factors, this framework aims to address tumor heterogeneity and immune evasion, ultimately improving patient outcomes through precision oncology.

Tissue-type plasminogen activator (tPA) is a serine protease that contains five functional domains, and it acts through influencing different substrates, binding proteins, and receptors. Studies revealed that tPA has been observed to have both neurotrophic and neurotoxic effects. It is still unclear how these opposite functions are modulated by tPA but the degree of maturity and/or the type of neurons, structure of the tPA, origin, and amount have been suggested as effective factors. The sole FDA-approved thrombolytic medication for acute ischemic stroke is tPA, yet worries about its limits still exist. Due to tPA’s limitations, conventional thrombolytic therapy for ischemic stroke by tPA occasionally results in problems or insufficient therapeutic effects. The results indicated that if tPA was given within the time latency window of up to 3 h it could significantly increase the propensity for cell survival. tPA’s ability to influence different cellular pathways suggest that targeting the desired ones could increase the therapeutic window of tPA in stroke recovery. To provide even better neuroprotection following an acute cerebral infarct, future therapeutics could focus on preventing the neurotoxic damage caused by tPA. In this review, we will discuss the current overview abroad tPA and the current knowledge concerning the natural history of tPA and aim to identify the relevant cellular signaling mechanisms underlying the tPA-mediated effects in-vitro. We also reviewed the present applications of several nanocarriers intended for the administration of tPA in ischemic strokes while also reviewing the biology, thrombolytic mechanism, and pleiotropic roles of tPA in the brain. We’ve also discussed the difficulties and the probable future of tPA-based Nano thrombolysis in stroke treatments.

Introduction: Virtual Reality (VR) is a promising distraction technique that immerses the participant in a 3-dimensional virtual presence. The purpose of this study is to investigate the effect of VR on reducing pain in adult patients during laceration repair in the emergency department (ED). Methods: This is a randomized clinical trial conducted in the EDs of Rasoul Akram, Haftom-e-Tir and Firouzgar hospitals, all under supervision of Iran University of Medical Sciences. A total of 160 patients with laceration that needed suturing were divided into two equal groups of 80 patients; One group received the VR glasses during the suturing while the other group did not receive them. All patients in both groups received local analgesics. The pain intensity of the patients before and after the intervention was obtained using a numerical scale (from 1 to 10). Patient satisfaction was measured in terms of pain reduction based on a Likert scale: 1=bad, 2=poor, 3=moderate, 4=good, 5=excellent. The collected data of pain intensity and patient satisfaction were compared before and after the intervention. Results: The average age of patients in the VR+ group and VR- group was 37.04 ± 17.21 and 39.18 ±5.09 years, respectively. The average pain intensity of VR+ patients before and after using VR glasses were 4.87 ± 1.2 and 2.13 ± 1.32, respectively, of which demonstrated a significant reduction in the pain intensity of VR+ patients (P-value =0.028). The level of VR+ patients' satisfaction in terms of pain intensity before and after using VR glasses was 1.44 ± 0.52 and 3.23 ± 0.64, respectively, indicating a significant increase in the patients' satisfaction in terms of pain reduction after using VR glasses (P-value =0.033). Conclusion: VR has a positive effect on attenuating patients' pain and increasing their satisfaction in terms of pain reduction.

Aim: COVID‐19 can lead to encephalopathy and loss of consciousness. This double‐blinded randomized clinical trial conducted in Tehran, Iran, aimed to assess the potential effectiveness of modafinil in patients with COVID‐19‐related encephalopathy.Methods: Nineteen non‐intubated COVID‐19 patients with encephalopathy were randomized into two groups: a treatment group receiving crushed modafinil tablets and a placebo group receiving starch powder. Modafinil was administered at a dose of 100 mg every 2 h, reaching a peak dosage of 400 mg. The level of consciousness was assessed using the Glasgow Coma Score (GCS) at multiple time points on the day of medication administration. The trial was registered under IRCT20170903036041N3 on 23/5/2021.Results: The average age in the modafinil and placebo groups was 75.33 and 70 years, respectively. No significant differences were observed between the two groups in terms of chronic conditions, clinical symptoms, or laboratory data. GCS scores were similar between the groups at baseline (p‐value = 0.699). After four doses of modafinil, GCS scores were slightly higher in the treatment group, but this difference was not statistically significant (p‐value = 0.581). GCS scores after each round of drug administration didn't significantly differ between the treatment and placebo groups (p‐value = 0.908).Conclusion: Modafinil exhibited a slight improvement in the level of consciousness among COVID‐19 patients with encephalopathy, although this improvement did not reach statistical significance when compared to the control group. Further research with larger sample sizes and longer treatment durations is recommended to explore modafinil's potential benefits in managing altered consciousness in COVID‐19 patients.

Introduction: Virtual Reality is a promising distraction technique immersing the participant in a 3-dimentional virtual presence. The purpose of this study is to investigate the effect of virtual reality on reducing pain in adult patients during laceration repair in the emergency department. Methods: This is a randomized clinical trial conducted in the emergency departments of Rasoul Akram, Haftom-e-Tir and Firozgar hospitals, all under supervision of Iran University of Medical Sciences. A total of 160 patients with laceration in need of suturing were divided into two equal groups of 80 patients; one group receiving virtual reality glasses during the suturing whilst the other group did not. All the patients in both groups received local analgesics. The pain intensity of the patients was obtained before and after the intervention using a numerical scale (from 1 to 10). The patients\' satisfaction in terms of pain reduction was measured based on the Likert scale score as: 1=bad, 2=poor, 3=moderate, 4=good, 5=excellent. The gathered data of both pain intensity and patient satisfaction was compared before and after the intervention. Results: The average age of patients in the VR+ group and VR- group was 37.04 ± 17.21 and 39.18 ± 5.09 years, respectively. The average pain intensity of VR+ patients before and after using VR glasses were 4.87 ± 1.2 and 2.13 ± 1.32, respectively, of which demonstrated a significant reduction in the pain intensity of VR+ patients (P-value =0.028). The level of VR+ patients\' satisfaction in terms of pain intensity before and after using VR glasses was 1.44 ± 0.52 and 3.23 ± 0.64, respectively, indicating a significant increase in the patients\' satisfaction in terms of pain reduction after using VR glasses (P-value =0.033). Conclusion: Virtual Reality has a positive effect on attenuating patients\' pain and increasing their satisfaction in terms of pain reduction.