The efficacy of conventional chemotherapy in solid tumors remains limited due to tumor microenvironment barriers that impede efficient drug transport and compromise therapeutic outcomes. Thermosensitive liposomes (TSLs) combined with focused ultrasound-induced hyperthermia offer a promising strategy for localized, temperature-triggered drug release. Despite experimental progress, a quantitative understanding of the coupled physical and biological mechanisms underlying this therapy is yet to be fully elucidated. Here, a three-dimensional multiphysics computational model was developed to investigate the interplay between focused ultrasound-induced hyperthermia and temperature-sensitive liposome-mediated drug delivery in solid tumors, integrating acoustic propagation, tissue heating and temperature-dependent drug release. Model predictions were validated against published experimental data, demonstrating good agreement with tumor growth and intratumoral drug concentration data. Sensitivity analysis showed that focused ultrasound parameters and liposome properties strongly influence treatment efficacy. Prolonged focused ultrasound exposure (20-30 min) produced greater tumor reduction than frequency variations (2-5 MHz). Treatment timing was also critical: For highly proliferating tumors, early therapy yielded markedly improved outcomes. Faster drug release kinetics enhanced intracellular drug accumulation and tumor regression. Intermediate-sized TSLs (~ 50 nm in radius) achieved optimal efficacy under moderate vascular permeability conditions, while larger liposomes (~ 65 nm in radius) were more effective in tumors with highly permeable vessels due to increased extravasation. This work provides a computational framework with predictive potential for optimizing the combined focused ultrasound-thermosensitive liposomes therapy and assisting to the design of thermally triggered nanocarriers.

Bladder cancer, particularly in older adults, poses significant therapeutic challenges due to its high recurrence rates, metastatic potential, and the toxicity associated with standard treatments. This case report describes a 75-year-old male with advanced muscle-invasive urothelial carcinoma of the bladder, exhibiting metastases to the prostate and lymph nodes. Following intolerance to conventional palliative chemotherapy, the patient underwent a structured integrative oncology protocol (systemic cancer therapies combined with adjuvant complementary therapies) that combined metabolic therapies, oncothermia, high-dose intravenous vitamin C, targeted nutraceutical supplementation, acupuncture, laser therapy, diet therapy, and yoga-based interventions. After initial metabolic optimization, an oral chemotherapy regimen comprising Afatinib, Axitinib, Relugolix, and Abiraterone was initiated. The patient demonstrated excellent tolerance to treatment, significant symptomatic relief, normalization of cancer-related biomarkers, and marked metabolic response with stable residual metabolic activity on PET-CT within six months. Quality of life measures improved substantially, and prognostic indices, including the Chuang Survival Score, reflected enhanced survival potential. This report underscores the potential of systemic cancer therapies along with integrative oncology to improve clinical outcomes, mitigate treatment-related toxicity, and enhance quality of life in advanced bladder cancer. While the findings are encouraging, they warrant validation through larger, controlled studies to better define the role of integrative approaches within the contemporary oncology framework.

Electrokinetically driven squeezing flows are of increasing relevance in biomedical transport and microscale pumping systems, particularly in understanding complex blood dynamics in constricted arteries. This study explores the electroosmotic bi-layered hybrid nano-blood flow through a cardiovascular squeezing channel, incorporating nanolayer and thermal slip effects. The lower layer consists of Casson-type non-Newtonian blood with SWCNTs and gold nanoparticles, while the upper layer is modeled as a Newtonian fluid. The controlling equations for various flow quantities are presented using nonlinear partial differential equations and subsequently converted to a scale-invariant form through scale-invariant transformations. The coupled nonlinear system is numerically resolved through the Runge-Kutta-Fehlberg (RKF45) approach in conjunction with a shooting scheme, executed in Mathematica to achieve stable and precise computational results. Results indicate that temperature enhances with increasing Hartmann number due to magnetic heating but diminishes with stronger interfacial ratio parameter. The Casson region exhibits more pronounced thermal and velocity gradients compared to the Newtonian region, reflecting physiological shear-thinning characteristics. This study employs an artificial neural network for rapid and precise evaluation of the skin friction coefficient demonstrating strong predictive accuracy with minimal error rates of 0.01%. These findings provide new insights into the interplay between electromagnetic and electroosmotic forces in nanofluidic blood transport. The model offers potential applications in optimizing targeted drug delivery, hyperthermia treatments and microvascular flow control in cardiovascular systems.

Tumor growth within physiological systems such as the gastrointestinal tract, ducts, or blood vessels can progressively obstruct fluid transport, impair organ function, and reduce the efficacy of therapeutic interventions like drug delivery and hyperthermia. In this study, a mathematical model is developed to investigate and characterize the mechanisms of peristaltic flow in a channel obstructed by transient tumor growth. The model incorporates fundamental conservation laws of mass and momentum, while a bump function is used to represent tumor-induced geometric deformation of the channel wall. In addition, a transverse magnetic field is introduced to account for magnetohydrodynamic effects relevant to biomedical applications such as magnetic hyperthermia. Tumor growth is modeled as a linear time-dependent process, and the flow is analyzed under low Reynolds number and lubrication theory assumptions, which are suitable for physiological flows. Analytical solutions are derived under simplified conditions to examine the influence of tumor growth rate and magnetic field strength on velocity distribution, pressure gradient, wall shear stress, streamline patterns and particle trajectories. The results suggest that early-stage tumor growth produces minimal flow disturbance, whereas progressive enlargement significantly obstructs flow, increases local pressure and skin friction and alters streamline patterns. An increase in Hartmann number enhances magnetic resistance, leading to a reduction in axial velocity and volumetric flow rate. Furthermore, parametric sensitivity analysis reveals that tumor geometric parameters play a dominant role in governing flow behavior compared with magnetic and peristaltic effects.

Malignant hyperthermia (MH) is a rare, life-threatening anesthetic complication caused by dysregulated skeletal muscle calcium homeostasis. We report a 25-year-old trauma patient who developed refractory hypotension with rising Etco2 despite progressive increases in minute ventilation, followed by hyperthermia, 2.5 hours after exposure to succinylcholine and sevoflurane. Hemodynamic instability was unresponsive to fluids and vasopressors but reversed rapidly after treatment for probable MH with dantrolene (Ryanodex). This case highlights early hemodynamic instability as a prominent manifestation of MH and emphasizes rising Etco2 despite increased ventilation as a critical diagnostic clue requiring prompt dantrolene administration.

Since the discovery of unique molecular building blocks (MBBs) such as tetraphenylethylene, aggregation-induced emission fluorescence imaging probes have witnessed revolutionary progress. For plasmon-free Raman imaging probes, the fundamental bottleneck is the discovery of unique Raman-active MBBs to improve the intrinsic scattering. We herein proposed a new concept of quencher-enhanced Raman scattering (QERS) based on nonfluorescent diammonium MBBs to fabricate bright Raman probes in second near-infrared window through improving rigid electronic resonance scattering while simultaneously suppressing concomitant fluorescence backgrounds. The home-made large π-conjugated diammonium quencher displays high photon-absorption but ultra-low fluorescence quantum yield (0.0001) under rigid resonant excitation at 1064 nm. Upon nanoprecipitation, these MBBs produce QERS probes with giant Raman cross-section (1.27 × 10[-19] cm[2]) as well as remarkable photostability, enabling high-precision Raman-guided surgical removal of tumor in living mice. Moreover, QERS probes achieve a high photothermal conversion efficiency up to 60.5%, allowing for effective hyperthermia ablation of drug-resistant bacteria in postsurgical infected wounds in the mice. QERS may suggest a robust and efficient strategy for developing plasmon-free Raman probes.

The complex immunosuppressive microenvironment of triple-negative breast cancer (TNBC) remains a major obstacle in attaining long-term clinical success and halting metastatic progression. To address this, the rational design of tumor microenvironment (TME)-responsive nanotheranostics is crucial for converting 'cold' tumors into 'hot' ones through synchronized imaging and precision therapy. Herein, we present a biomimetic, stimuli-activatable assembly (Au/Ag@HMON-NLG@CCM) utilizing a H2O2-responsive Au/Ag core to facilitate NIR-II ratiometric photoacoustic (PA) detection and thermal ablation. By encapsulating the IDO inhibitor NLG919 within a hollow mesoporous organosilica (HMON) shell and coating with cancer cell membrane (CCM), the system achieves superior tumor-targeting and synergistic immuno-photothermal effects. Specifically, TME-overexpressed H2O2-induces the oxidative degradation of the Ag, shifting the absorption into the NIR-II window to enable robust ratiometric PA visualization and efficient PTT (η = 42.8%). The resulting hyperthermia triggers immunogenic cell death (ICD) to initiate antigen release, while NLG919-mediated IDO1 blockade alleviates local immunosuppression, collectively remodeling the 'cold' TME. In bilateral tumor models, this integrated strategy effectively suppresses both primary lesions and distant metastases, demonstrating a potent systemic abscopal effect and durable antitumor immunity. Overall, this multifunctional nanoplatform provides a transformative strategy for NIR-II-guided precision medicine, offering a robust approach to eradicating metastatic and immunosuppressive malignancies.

Anti-angiogenesis therapy has offered an innovative strategy to fight gastric cancer (GC) in the clinic. However, the systemic acquired resistance, low drug specificity, as well as diffusional hindrance of agents to the tumor site severely limit this mono-therapeutic method. To overcome the obstacles, we design and prepare a parallel targeted nanoplatform (Src-I1/CR NPs), which is self-assembled by Src kinase inhibitor (Src-I1) and near-infrared (NIR) phototherapeutic agent (CR) to fight GC. Under laser irradiation, the Src-I1/CR NPs can induce localized cellular apoptosis with mitochondrial and lysosomal damage, triggering excellent GC hyperthermia-ablation. Simultaneously, the nano-conjugate blocks the Src/STAT3/VEGF pathway to activate the anti-angiogenesis effect for tumor starving by inhibiting the supply of nutrients and oxygen. More importantly, Src-I1/CR NPs also restrain the Src-mediated PI3K/AKT pathway to comprehensively suppress cancer cell proliferation, invasion, and migration. Overall, multimodal NIR Src-I1/CR NPs initiate precise parallel targeting cancer cells with serious mitochondrial and lysosomal dysfunction as well as desired cellular apoptosis for augmented photo-ablation, which offers a promising avenue in further GC preclinical investigation.

The development of small molecule-based nanoagents that simultaneously possess an ultrahigh extinction coefficient, bright near-infrared IIb (NIR-IIb, 1500-1700 nm) fluorescence emission, efficient reactive oxygen species (ROS) generation in hypoxic microenvironments, and excellent photothermal performance is of considerable importance for high-efficiency phototheranostics, yet it remains difficult to realize in a single system. Herein, a tactic centering on "regulating the electron-donating ability of the weak donor (D) unit" is applied for the construction of small molecules with enhanced light-harvesting capability, thereby optimizing fluorescence emission and photodynamic/photothermal performances. As a proof-of-concept, by coupling the strong acceptor (A) and D' moieties with different weak D moieties, three A-D'-D-D'-A type molecules (DP2F, DPOF, and DP2O) are designed. Compared to DP2F and DPOF, the maximum absorption wavelength of DP2O exhibited an obvious redshift due to the enhanced electron-donating ability of the D unit. Notably, the corresponding DP2O nanoparticles (NPs) possess an ultrahigh extinction coefficient (ε) of (2.6 ± 0.1) × 10[5] M[-1] cm[-1] at 831 nm. To the best of our knowledge, this value of ε is considerably higher than those of most reported organic nanomaterials. Consequently, the DP2O NPs exhibited strong NIR-IIb fluorescence emission, enabling high-resolution in vivo imaging of the whole vessel network and tumors. Moreover, the DP2O NPs displayed satisfactory type-I/II ROS generation and hyperthermia induction, leading to efficient inhibition of tumor growth in vivo.

Background and aim Diabetes is the main cause of foot ulcers and limb amputation. The primary aim of our study was to identify clinical risk factors for the development of foot ulcers in patients with diabetes. The secondary aim was to evaluate the benefits of using a thermal camera and AI to detect feet at high risk of developing foot ulcers. Methods A two-year prospective study was conducted including all diabetic patients admitted to the endocrinology department at Mohammed VI University Hospital of Agadir. Data were collected from patient records, and thermal imaging was performed in all diabetic patients, with or without foot ulcers, after obtaining informed consent. Results The study included 158 diabetic patients admitted to the endocrinology department at Mohammed VI University Hospital of Agadir. Foot ulcer prevalence was 14.6% (n = 23). In patients with ulcers, the average age was 51 years, with a predominance of males (56%) (n = 13); the average time since diagnosis of diabetes was 6.5 years. High blood pressure was found in 26% (n = 6) of the patients, hyperlipidemia in 30% (n = 7), smoking in 47% (n = 11), and overweight in 34% (n = 8), with an average body mass index of 27 kg/m², poor diabetes control with an average hemoglobin A1c of 11%, and a high average fasting blood glucose level of 3.6 g/L. Foot examination of patients with ulcers revealed neuropathy in 86% (n = 20) and peripheral artery disease with a low ankle-brachial index in 82% (n = 19). We found that 56% (n = 13/23) of the patients with ulcers had a positive thermal imaging delta on admission, with an average delta of 3.3 ± 0.6 °C. In the group of patients with ulcers, a statistically significant correlation was found with smoking (p = 0.001), overweight (p = 0.017), poor glycemic control (p = 0.002), diabetic retinopathy (p < 0.001), diabetic neuropathy (p < 0.001), peripheral artery disease (p < 0.001), and foot deformity (p < 0.001). Finally, high thermal delta was found to be significantly more common in the ulcer group (p < 0.001). Conclusions Evaluating a foot at risk of ulceration requires time and trained medical staff, making thermal imaging cameras useful for detecting hyperthermia 15 days before an ulcer appears. The assessment of a diabetic foot at risk of developing an ulcer requires a physical examination to identify the main risk factors in our study: neuropathy, arteriopathy, and foot deformity. Hyperthermia detected by a thermal imaging camera is a new marker that may enable the early detection of foot ulcers, allowing earlier intervention to prevent amputations.

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening hypermetabolic reaction to dopamine-antagonist drugs that may progress to profound rhabdomyolysis, extreme hyperkalemia, and cardiac arrest (CA). Evidence guiding extracorporeal cardiopulmonary resuscitation (ECPR) for metabolic or toxic etiologies is scarce, and its use in NMS has not yet been described. We report the case of a 23 year old woman who presented with hyperthermia, severe muscular rigidity and laboratory evidence of NMS. In the emergency-department arrival she developed witnessed asystolic CA, unresponsive to conventional treatment. After a transient return of spontaneous circulation and a second refractory CA, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) was initiated. Continuous hemodiafiltration facilitated rapid correction of extreme hyperkalemia, whereas dantrolene and active cooling normalized core temperature. Valid cardiac activity recovered after 36 hours, allowing ECMO weaning. However, devastating hypoxic-ischemic brain injury led to brain death, which was declared on day 5. Heart and liver procurement for transplantation were successfully performed. To our knowledge, implementation of ECPR in the context of NMS was not previously documented in the literature. Our case suggests that timely V-A ECMO might bridge extreme hyperkalemic arrest to cardiac recovery, offering both a chance of patient survival and, when neurological prognosis is dismal, an opportunity for organ donation.