To assess the effect of cycloplegia on keratometry and horizontal white to white (WTW) measurements in presbyopic patients with type 2 diabetes.

The post-hoc analysis included 88 eyes from 88 patients with type 2 diabetes aged >40 years. Flat keratometry (Kf), steep keratometry (Ks), mean keratometry (Km), corneal astigmatism (CA), and WTW were measured using the RC-5000 auto kerato-refractometer (Tomey Inc., Nagoya, Japan), before and thirty minutes after the instillation of two drops (administered five minutes apart) of either 0.5% (46 patients) or 1% tropicamide (42 patients).

The mean changes in Kf, Ks, Km, CA, and WTW were - 0.01 ± 0.26 D, -0.05 ± 0.23 D, -0.03 ± 0.19 D, -0.04 ± 0.31 D, and 0.05 ± 0.24 mm, respectively, in the 0.5% tropicamide group. These values were - 0.07 ± 0.28 D, 0.01 ± 0.23 D, -0.03 ± 0.21 D, 0.08 ± 0.29 D, and 0.04 ± 0.15 mm, respectively, in the 1% tropicamide group. The changes following cycloplegia were not statistically significant (P ˃ 0.05).

Post-cycloplegia keratometry and WTW measurements were comparable to pre-cycloplegia values in presbyopic patients with type 2 diabetes, suggesting that these measurements can be reliably obtained after cycloplegia.

IRCT.ir, registration number: IRCT20200829048553N1, 2021-05-31.

gov, ID: NCT04932213, 2021-06-21.

Kounis syndrome-an acute coronary syndrome occurring in the setting of allergic or hypersensitivity reactions-remains an under-recognised clinical entity. In many cases, the diagnosis is largely probabilistic, particularly in the absence of confirmatory evidence such as mast-cell activation markers or intracoronary imaging. In the present context, while the clinical history of bee sting strongly supports Kounis syndrome as the most likely differential diagnosis, definitive confirmation is limited by the lack of objective mast-cell-related investigations. We report a 72-year-old man with hypertension and diabetes mellitus, a reformed smoker, who presented following multiple (three to four) bee stings localised to the right shoulder. At presentation, he exhibited features limited to a local allergic reaction, with no evidence of systemic involvement or anaphylaxis. He was managed with sting removal, antihistamines, and analgesics, and remained asymptomatic and stable on continuous monitoring during a 12-hour observation period. He was subsequently discharged in stable condition. Approximately one hour post-discharge, he became unresponsive at home, and bystander cardiopulmonary resuscitation (CPR) was initiated. On arrival at the emergency department, he was found to be in asystole. Advanced cardiac life support was continued, and return of spontaneous circulation (ROSC) was achieved. Post-resuscitation electrocardiography revealed inferior ST-elevation myocardial infarction with reciprocal changes. Bedside echocardiography demonstrated inferior wall hypokinesia with a left ventricular ejection fraction of 40%. Coronary angiography showed complete occlusion of the mid-right coronary artery with a non-obstructive left coronary system. A drug-eluting stent was successfully deployed, restoring TIMI 3 flow. However, approximately four to five hours after successful revascularisation, the patient developed refractory ventricular arrhythmias and succumbed despite ongoing resuscitative efforts.

This case highlights a temporally plausible, though not definitively established, instance of delayed probable Type II Kounis syndrome following an apparently mild, local Hymenoptera sting reaction. It underscores the need for continued vigilance for delayed coronary events even after seemingly benign allergic presentations, and emphasises the inherent challenge of distinguishing Kounis syndrome from conventional atherosclerotic ST-elevation myocardial infarction in the absence of confirmatory allergic or mechanistic evidence.

This study aimed to examine the relationship between type 1 diabetes mellitus (T1DM) and dental caries among children and adolescents through a meta-analysis, and to assess the potential causal link between these conditions using Mendelian randomization (MR) techniques.

A comprehensive literature review was carried out to identify relevant studies, and meta-analyses were conducted utilizing Stata statistical software. For the MR analyses, summary-level data from genome-wide association studies (GWAS) regarding T1DM and dental caries in childhood and adolescence were gathered.

The meta-analysis indicated that the decayed, missing, and filled teeth (DMFT) index for permanent teeth was notably higher in children with T1DM compared to the control group, yielding a pooled standardized mean difference (SMD) of 0.19 (95% CI: 0.06-0.31; I² = 26.6%). However, the MR analysis did not reveal a significant causal relationship between T1DM and the prevalence of dental caries in children and adolescents (OR = 0.98, 95% CI: 0.94-1.02, P = 0.308).

While children and adolescents with T1DM are at an elevated risk for dental caries, no statistically significant causal link was observed.

https://www.crd.york.ac.uk/PROSPERO/view/177851 identifier CRD2020177851.

Programmed death 1 (PD-1) inhibitors have transformed the treatment of advanced non-small cell lung cancer (NSCLC), but durable responses remain limited to a subset of patients. Conventional biomarkers, including PD-L1 expression and tumor mutational burden, are constrained by tissue accessibility, intratumoral heterogeneity, and limited capacity for dynamic monitoring. Circulating cytokines offer a minimally invasive alternative because they reflect systemic inflammation, antitumor immunity, and treatment-related immune activation. Evidence indicates that serum levels and on-treatment changes in TNF-α, IFN-γ, IL-6, IL-8, IL-17A, IL-1β, IL-2, IL-5, and IL-10 are associated with response, survival, and immune-related adverse events during PD-1 blockade. In general, declines in IL-6, IL-8, IL-17A, and IL-10, together with transient increases in IFN-γ and TNF-α, may indicate favorable immune reinvigoration, although findings remain inconsistent across studies. This review summarizes the biological functions, mechanistic roles, and clinical relevance of circulating cytokines as dynamic biomarkers, evaluates their potential values and current limitations in predicting the efficacy of PD-1 inhibitor therapy in NSCLC.

Because of its limited treatment choices and high recurrence rates, bladder cancer (BCa) presents a significant clinical issue. As a result, current research is concentrated on creating novel approaches for early diagnosis and more specialized treatments. Nanorobots hold significant potential as precise medicine-delivery systems and as in situ diagnostic vectors within this dynamic environment. Personalized treatments are becoming increasingly feasible thanks to new insights into the molecular pathways driving tumor growth, revealed through studies on exosomes and non-coding RNAs (ncRNAs), however, their true potential lies in integrating these findings. This review analyzes the role of nanorobots, exosomes and ncRNAs in BCa and, more importantly, proposes a synergistic framework where active nanorobots are used for the targeted delivery of therapeutic exosomes (loaded with ncRNAs), overcoming the physiological limitations of intravesical administration. The interplay between nanorobots, exosomes and ncRNAs outlines a coherent and synergistic therapeutic approach with nanorobots enabling active navigation, exosomes offering stable and biocompatible loading, and ncRNAs providing the precision molecular functions required for targeted intervention. Their integration constitutes the core rationale driving this emerging approach and this technological convergence may open new avenues for precision diagnosis and targeted therapy. Incorporating these state-of-the-art technologies could ultimately transform the treatment of BCa and greatly enhance patient outcomes and quality of life. The aim of this review is to evaluate the current evidence on these three technologies and to define an integrated strategy that addresses existing clinical barriers and advances precision medicine in BCa.

Background: While radical cystectomy is standard for muscle-invasive bladder cancer (MIBC), micrometastasis-related recurrence is common. Cisplatin-based neoadjuvant therapy (NAT) confers modest benefits, while immune checkpoint inhibitors (ICIs) provide new efficacy-enhancing strategies. This study aims to compare the efficacy and safety of ICIs with chemotherapy (NAC-ICI), neoadjuvant chemotherapy (NAC), and no neoadjuvant therapy (NNAT). It also explores potential biomarkers predictive of NAT response and evaluates the real-world efficacy of NAC-IC. Method: This single-center retrospective analysis included 80 radical cystectomy patients, with 51 NNAT group and 29 in the NAT group. Survival outcomes were evaluated by Kaplan-Meier survival curves, with log-rank test and restricted mean survival time (RMST) for comparisons. Pathological responses were assessed by complete response (pCR) and downstaging (pDS). Treatment-related adverse events (TRAEs) and predictive hematological biomarkers were analyzed. Results: Kaplan-Meier curves showed NAT is non-significant survival advantage over NNAT (p = 0.30). The RMST analysis showed the NAC-ICI had significantly longer RMST than the NNAT (56.00 vs. 47.73 months; Δ = +8.27 months; p = 0.0008). Fisher's exact test showed that NAC-ICI had a numerically higher pCR rate (42.10%) than NAC (20.00%), but the difference was non-significant (p = 0.414) ROC analysis showed baseline platelet count (PLT) was a significant negative predictor of pCR after NAC-ICI. Conclusions: This study indicates potential feasibility and safety of NAT for MIBC patients. Chemoimmunotherapy trends toward better pathological and survival outcomes than chemotherapy alone, but no statistically significant differences were observed. Baseline PLT may be a potential prdictive biomarker.

Backgrounds: Fruquintinib is a selective vascular endothelial growth factor receptor (VEGFR)-1/2/3 inhibitor approved for previously treated metastatic colorectal cancer. As its use expands across gastrointestinal (GI) malignancies and combination regimens, randomized evidence is needed to define the toxicity profile most relevant to clinical monitoring, particularly hypertension, dermatologic toxicity, renal toxicity, bleeding, and thrombotic events. The objective of this study was to synthesize randomized controlled trial evidence to quantify the incidence and relative risk of key toxicities associated with fruquintinib in gastrointestinal malignancies. Methods: MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception through 1 January 2026 for phase II-III randomized controlled trials of fruquintinib in GI cancers reporting hypertension, proteinuria, hemorrhage, venous thromboembolism (VTE), and hand-foot skin reaction or palmar-plantar erythrodysesthesia (HFSR/PPE). Trial-reported CTCAE adverse events were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using Mantel-Haenszel random-effects models. Exploratory subgroup analyses were performed in metastatic colorectal cancer (mCRC). Results: Four randomized trials (n = 1872) were included. Fruquintinib significantly increased grade ≥3 hypertension (RR 9.01, 95% CI 4.67-17.40) and grade ≥3 HFSR/PPE (RR 26.00, 95% CI 6.42-105.29). Any-grade proteinuria was also increased (RR 1.89, 95% CI 1.30-2.74). Grade ≥3 hemorrhage occurred at low absolute rates and was numerically higher with fruquintinib, but the pooled estimate did not reach statistical significance (RR 1.82, 95% CI 0.92-3.61). VTE estimates were imprecise because of sparse events (any-grade VTE: RR 1.23, 95% CI 0.53-2.88; grade ≥3 VTE: RR 1.96, 95% CI 0.52-7.36). Conclusions: In randomized evidence across GI malignancies, the principal safety signals associated with fruquintinib are grade ≥3 hypertension and grade ≥3 HFSR/PPE, together with increased any-grade proteinuria. Grade ≥3 hemorrhage was uncommon and numerically higher, whereas VTE estimates remained imprecise. These findings support early blood pressure optimization, proactive dermatologic management, routine urinalysis monitoring, and individualized assessment of bleeding and thrombotic risk when initiating therapy.

Bladder cancer (BC) is a prevalent malignancy characterized by a high recurrence rate and the necessity for long-term surveillance demands, creating a need for accurate yet practical tools for early detection and monitoring. While current standards including cystoscopy, urinary cytology, and imaging remain indispensable, their clinical utility is constrained by invasiveness, suboptimal sensitivity for selected lesions or low-grade lesions, inter-observer variability, and cumulative costs. Currently, biomarker research has expanded from single protein assays to multi-analyte strategies encompassing DNA, RNA, proteins, extracellular vesicle-associated cargo, and metabolomics signatures. This review synthesizes recent advances in diagnostic, surveillance, prognostic, and treatment-predictive biomarkers, with emphasis on assay principles, analytical platforms and reported performance where available. Furthermore, we delineate critical barriers to translation, including limited prospective multicenter validation, heterogeneous pre-analytical workflows, inconsistent thresholds, and the persistent trade-off between sensitivity and specificity in real-world benign urologic conditions. Ultimately, while emerging biomarkers and multi-omics panels hold transformative potential as non-invasive adjuncts in risk-adapted clinical pathways, their routine adoption is contingent upon rigorous clinical integration and standardized validation.

Cervical cancer remains a leading cause of cancer death in women, and outcomes in recurrent or metastatic disease remain poor despite chemoradiation and bevacizumab. The HPV-driven biology that defines the disease-viral E6/E7 oncoproteins, an inflamed microenvironment and exploitable surface antigens-has enabled a rapid expansion of novel systemic therapies, yet existing reviews tend to catalogue these agents by class or report individual trials in isolation, leaving their comparative efficacy, safety and clinical positioning unresolved. Here we organise emerging anti-tumour agents by mechanism of action and array them along a translational maturity gradient, from approved regimens through phase 1/2 candidates to preclinical assets, appraising efficacy and safety in parallel. We cover immune checkpoint inhibitors, bispecific antibodies, antibody-drug conjugates (ADCs), therapeutic HPV vaccines and adoptive cell therapy, and integrate China-developed agents-including the PD-1/CTLA-4 bispecific cadonilimab and the Nectin-4 conjugate 9MW2821-into the global landscape. Departing from a purely descriptive account, we compare class-specific toxicity profiles and predictive biomarkers side by side and, most importantly, translate the fragmented evidence into a resistance-directed treatment framework anchored on platinum-resistant disease. We further argue that, because access to newly approved agents varies widely between health systems, the line of therapy at which an agent is introduced-rather than its approval status alone-may influence survival, a decision-relevant question that current guidelines leave unanswered. This mechanism-based, decision-oriented synthesis is intended to guide rational agent selection, sequencing and combination strategy across diverse clinical settings.

Objectives: MET inhibitors have demonstrated clinical efficacy in several MET-driven malignancies; however, their therapeutic potential in pancreatic cancer remains insufficiently characterized. This study aimed to evaluate the antitumor activity of the selective MET inhibitor savolitinib in MET-high pancreatic cancer and to investigate the role of autophagy in the cellular response to MET inhibition. Methods: MET-high pancreatic cancer cell lines (AsPC-1 and BxPC-3) were treated with savolitinib. Cell viability, apoptosis, transcriptomic profiling, and signaling pathway analyses were performed to characterize its antitumor effects and underlying mechanisms. Autophagy induction was assessed using monodansylcadaverine (MDC) staining, transmission electron microscopy, lysosomal co-localization analysis, and western blotting of autophagy-related markers. The therapeutic efficacy of combining savolitinib with the autophagy inhibitor chloroquine was further evaluated in vitro and in BxPC-3 xenograft models. Results: Savolitinib significantly inhibited MET phosphorylation and reduced the viability of MET-high pancreatic cancer cells while inducing apoptosis, as evidenced by increased levels of cleaved PARP, cleaved caspase-3, and an elevated Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio. Transcriptomic analysis revealed significant enrichment of autophagy-related pathways among savolitinib-responsive genes. Savolitinib induced autophagy-associated vesicular changes and autophagic flux, accompanied by suppression of AKT/mTOR signaling. Pharmacological inhibition of autophagy with chloroquine markedly enhanced savolitinib-induced apoptosis in vitro and significantly improved tumor growth inhibition in vivo, achieving a tumor growth inhibition rate of 84.96% in the combination-treatment group without obvious systemic toxicity under the tested conditions. Conclusion: Savolitinib-induced autophagy functions as an adaptive cytoprotective response in MET-high pancreatic cancer. Combined inhibition of MET and autophagy enhances antitumor activity and warrants further evaluation in MET-high pancreatic cancer models.