Search Results (456)

Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) and autoimmune hemolytic anemia (AIHA) are both life-threatening hematologic syndromes that rarely present together outside of malignancy. Advanced acquired immunodeficiency syndrome (AIDS) creates a milieu of profound immune dysregulation and hyperinflammation, predisposing patients to atypical overlaps of these disorders. Case Presentation: A 30-year-old woman with poorly controlled AIDS presented with three weeks of jaundice, fever, and fatigue. Initial labs revealed pancytopenia, hyperbilirubinemia, and elevated ferritin level. Direct anti-globulin testing confirmed warm AIHA (IgG⁺/C3d⁺) with transient cold agglutinins. Despite intravenous immunoglobulin (IVIG), rituximab, and transfusions, she developed hepatosplenomegaly, extreme hyperferritinemia, and sIL-2R > 10,000 pg/mL, meeting HLH-2004 criteria. Bone marrow biopsy excluded malignancy; further work-up revealed Epstein–Barr virus (EBV) viremia and cytomegalovirus (CMV) reactivation. Dexamethasone plus reduced-dose etoposide transiently reduced soluble interleukin-2 receptor (sIL-2R) but precipitated profound pancytopenia, Acute respiratory distress syndrome (ARDS) from CMV/parainfluenza pneumonia, bilateral deep vein thrombosis (DVT), and an ST-elevation myocardial infarction (STEMI). She ultimately died of hemorrhagic shock after anticoagulation despite maximal supportive measures. Conclusions: This case underscores the diagnostic challenges of HLH-AIHA overlap in AIDS, where cytopenias and hyperferritinemia mask the underlying cytokine storm. Pathogenesis likely involved IL-6/IFN-γ overproduction, impaired cytotoxic T-cell function, and molecular mimicry. While etoposide remains a cornerstone of HLH therapy, its myelotoxicity proved catastrophic in this immunocompromised host, highlighting the urgent need for cytokine-targeted agents to mitigate treatment-related mortality. Full article

Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is challenging this perception, highlighting a potentially critical role for the immune system in STS biology. Objective: Building on our previous findings suggesting impaired natural killer (NK) cell activity in STS patients, we aimed to perform an in-depth characterization of peripheral NK cells in STS. Methods: Peripheral blood samples from STS patients and sex- and age-matched healthy donors were analyzed to assess NK cell degranulation, IFNγ production, and receptor repertoire. Results: Functional assays revealed a notable reduction in both degranulation and IFNγ production in NK cells from STS patients. STS patients also exhibited dysregulated expression of activating and inhibitory NK cell receptors. Principal component analysis (PCA) identified CD27 and NKp44 as critical markers for distinguishing STS patients from healthy donors. Increased CD27 expression represents a shift towards a more regulatory NK cell phenotype, and we found that CD27 expression was negatively correlated with NK cell degranulation and IFNγ production. ROC curve analysis demonstrated strong potential to distinguish between the groups for both CD27 (AUC = 0.85) and NKp44 (AUC = 0.94). Conclusion: In conclusion, STS patients exhibited impaired NK cell function, altered receptor repertoire, and a shift towards a less cytotoxic and more regulatory phenotype. Full article

Cold-water immersion (CWI), as a common recovery method, has been widely used in the field of post-exercise fatigue recovery. However, there is still a lack of comprehensive and systematic scientific evaluation of the combined effects of cold-water immersion combined with other therapies (CWI + Other). The aim of this study was to compare the effects of CWI and CWI + Other in post-exercise fatigue recovery and to explore the potential benefits of CWI + Other. We systematically searched PubMed, Embase, Web of Science, Cochrane Library and EBSCO databases to include 24 studies (475 subjects in total) and performed a meta-analysis using standardized mean difference (SMD) and 95% confidence intervals (CIs). The results showed that both CWI + Other (SMD = −0.68, 95% CI: −1.03 to −0.33) and CWI (SMD = −0.37, 95% CI: −0.65 to −0.10) were effective in reducing delayed-onset muscle soreness (DOMS). In subgroup analyses of athletes, both CWI + Other (SMD = −1.13, 95% CI: −1.76 to −0.49) and CWI (SMD = −0.47, 95% CI: −0.87 to −0.08) also demonstrated significant effects. In addition, CWI + Other significantly reduced post-exercise C-reactive protein (CRP) levels (SMD = −0.62, 95% CI: −1.12 to −0.13), and CWI with water temperatures higher than 10 °C also showed a CRP-lowering effect (MD = −0.18, 95% CI: −0.30 to −0.07), suggesting a potential benefit in anti-inflammation. There were no significant differences between the two interventions in the metrics of creatine kinase (CK; CWI: SMD = −0.01, 95% CI: −0.27 to 0.24; CWI + Other: SMD = 0.26, 95% CI: −0.51 to 1.03) or countermovement jump (CMJ; CWI: SMD = 0.22, 95% CI: −0.13 to 0.57; CWI + Other: SMD = 0.07, 95% CI: −0.70 to 0.85). Full article

Accurate prediction of drug–drug interactions (DDIs) is essential for ensuring medication safety and optimizing combination-therapy strategies. However, existing DDI models face limitations in handling interactions related to stereochemistry and precisely locating drug interaction sites. These limitations reduce the prediction accuracy for conformation-dependent interactions and the interpretability of molecular mechanisms, potentially posing risks to clinical safety. To address these challenges, we introduce LSA-DDI, a Spatial-Contrastive-Attention-Based Drug–Drug Interaction framework. Our 3D feature extraction method captures the spatial structure of molecules through three features—coordinates, distances, and angles—and fuses them to enhance the model of molecular spatial structures. Concurrently, we design and implement a Dynamic Feature Exchange (DFE) mechanism that dynamically regulates the flow of information across modalities via an attention mechanism, achieving bidirectional enhancement and semantic alignment of 2D topological and 3D spatial structure features. Additionally, we incorporate a dynamic temperature-regulated multiscale contrastive learning framework that effectively aligns multiscale features and enhances the model’s generalizability. Experiments conducted on public drug databases under both warm-start and cold-start scenarios demonstrated that LSA-DDI achieved competitive performance, with consistent improvements over existing methods. Full article

Botulism is a severe muscle paralysis disease mediated by the botulinum toxin. Here, we reported a foodborne botulism case caused by Clostridium botulinum subtype A5(b3) from self-packaged vacuum spicy rabbit heads. Treatment for this case was delayed due to misdiagnosis and insufficient diagnostic capacity in three hospitals, which resulted in progressive clinical deterioration, and eventually, the patient was transferred to Shandong Public Health Clinical Center for specialized therapy. The case was suspected as foodborne botulism by the Qilu Medical-Prevention Innovation Integration pathway and multi-disciplinary consultation. An epidemiological investigation and laboratory confirmation revealed that the botulinum neurotoxin originated from vacuum-packaged spicy rabbit heads distributed via interprovincial cold chain logistics. After treatment with botulism antiserum, the patient’s condition significantly improved, and they were discharged after recovery. We revealed that this foodborne botulism outbreak was caused by the Clostridium botulinum A5(b3) subtype from food by whole-genome sequencing and SNP typing. All the strains belonged to Group I carrying the botulinum neurotoxin gene classified as the ha cluster. Toxin A was confirmed by MBA and other methods, while toxin B was non-functional due to the truncated bont/B gene. Other virulence genes and antibiotic resistance genes were also detected. Our findings indicate that self-packaged vacuum meat products represent an emerging risk factor for botulism transmission when stored improperly. Importantly, the recurrent misdiagnosis in this case underscored the urgent need to enhance the training of healthcare professionals in medical institutions to improve the diagnostic accuracy and clinical management of botulism. Full article

(1) Objective: Cold atmospheric plasma (CAP) is a safe and effective alternative to radiotherapy for cancer treatment. Its anticancer effects are attributed to increased intracellular reactive oxygen species (ROS). Glutathione, a key antioxidant derived from glutamine, is critical for cell proliferation. This study investigated whether CAP-induced ROS elevation results from reduced glutamine–glutathione conversion and elucidates the underlying mechanisms. (2) Methods: Using esophageal squamous carcinoma cell models (Ec9706 and Eca109), we analyzed CAP’s effects on key enzymes in glutamine metabolism (Glutaminase 1 and γ-glutamylcysteine ligase) and proliferation-related genes (e.g., Retinoblastoma and Nuclear respiratory factor 2). Transcriptome analysis further explored molecular pathways involved in CAP-mediated anticancer effects. (3) Results: CAP reduced Glutaminase 1 and γ-glutamylcysteine ligase expression, leading to lower intracellular glutathione, higher ROS activity, and enhanced apoptosis. Transcriptome data confirmed CAP’s role in oxidation-reduction reactions and glutamine metabolism. (4) Conclusions: This study provides the first mechanistic insights into CAP’s anticancer effects by targeting glutamine metabolism. While based on in vitro assays, these findings guide the development of novel CAP therapies for currently incurable cancers. Full article

Cold atmospheric plasma (CAP) interacts with tissues, leading to fast wound disinfection. Given the frequent global burden of burn injuries and the risks of infection associated with acute full-thickness burns (FTBs), this investigation examined CAP as a potential therapeutic method for wound healing due to its antimicrobial and pro-healing effects. Here, we examined the impacts of CAP on the healing of wounds resulting from acute FTSBs. We established an animal model that included four groups: (1) healthy control animals without burns, (2) untreated animals with acute FTSBs, (3) animals with acute FTSBs treated with CAP for 5 s per day for 21 days, and (4) animals with acute FTSBs treated with CAP for 10 s per day for 21 days. Wound healing was assessed using immunohistological methods. In animals with FTSBs, CAP therapy was accompanied by (i) accelerated wound closure, (ii) enhanced regeneration of the dermis and epidermis, and (iii) increased protein expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF). These changes were more pronounced following CAP treatment for 10 s per day compared to CAP treatment for 5 s per day. Full article

Background: Glioblastoma (GBM) resists current therapies due to its rapid proliferation, diffuse invasion, and heterogeneous cell populations. We previously showed that a single cold atmospheric plasma discharge tube (DT) reduces GBM viability via broad-spectrum electromagnetic (EM) emissions. Here, we tested whether two DTs arranged in a helmet configuration could generate overlapping EM fields to amplify the anti-tumor effects without thermal injury. Methods: The physical outputs of the single- and dual-DT setups were characterized by infrared thermography, broadband EM field probes, and oscilloscope analysis. Human U87-MG cells were exposed under the single or dual configurations. The viability was quantified with WST-8 assays mapped across 96-well plates; the intracellular reactive oxygen species (ROS), membrane integrity, apoptosis, and mitochondrial potential were assessed by multiparametric flow cytometry. Our additivity models compared the predicted versus observed dual-DT cytotoxicity. Results: The dual-DT operation produced constructive EM interference, elevating electric and magnetic field amplitudes over a broader area than either tube alone, while temperatures remained <39 °C. The single-DT exposure lowered the cell viability by ~40%; the dual-DT treatment reduced the viability by ~60%, exceeding the additive predictions. The regions of greatest cytotoxicity co-localized with the zones of highest EM field overlap. The dual-DT exposure doubled the intracellular ROS compared with single-DT and Annexin V positivity, confirming oxidative stress-driven cell death. The out-of-phase operation of the discharge tubes enabled the localized control of the treatment regions, which can guide future treatment planning. Conclusions: Two synchronously operated plasma discharge tubes synergistically enhanced GBM cell killing through non-thermal mechanisms that coupled intensified overlapping EM fields with elevated oxidative stress. This positions modular multi-DT arrays as a potential non-invasive adjunct or alternative to existing electric-field-based therapies for glioblastoma. Full article

Background: The aim of this study was to evaluate the effect of Photobiomodulation Therapy (PBMT) on the eruption rate of impacted maxillary canines after surgery, using a split-mouth design. Methods: A 16-year-old patient was referred to the Department of Oral and Maxillo-Facial Sciences of “Sapienza” University of Rome. Clinical examination revealed the persistence of maxillary primary canines and the absence of a palpable canine bump. CBCT scans confirmed that both upper permanent canines were impacted in the palatal osteomucosal region and showed a mesial inclination. Conventional surgery with cold blade was performed for both impacted canines, and PBMT was applied on element 2.3 for three sessions after surgery. Since this is a case report, no statistical analysis was performed. Results: The eruption movement of the two impacted canines was evaluated 16 weeks after surgery. The extent of the spontaneous eruption movement of element 1.3 was 0.21 mm, while element 2.3, which underwent three sessions of PBMT following surgery, moved 3.16 mm. Conclusions: The element that underwent PBMT appears to respond positively in terms of spontaneous eruption following disinclusion surgery compared to the contralateral element that was not stimulated with the laser. These findings suggest that photobiomodulation therapy could be effective in accelerating the eruption of palatally impacted canines following surgery, avoiding the need to use orthodontic traction. Future randomized controlled clinical trials are needed to demonstrate these preliminary results. Full article

Background/Objectives: Actinic keratosis (AK) occurs on sun-damaged skin and is considered a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) and red light, is a common treatment for AK. However, its clinical efficacy for invasive tumors such as SCC is limited by the poor penetration and distribution of the photosensitizer. Cold atmospheric plasma (CAP), a partially ionized gas, increases skin permeability and exhibits anti-cancer properties through the generation of reactive oxygen species (ROS). In a previous study, CAP showed promising synergistic effects when combined with ALA-PDT for the treatment of SCC cells in vitro. The present study investigated the effects of combining CAP with ALA-PDT on cutaneous AK and SCC induced by ultraviolet B (UV-B) irradiation in SKH1 hairless mice. Methods: We compared various application sequences (CAP-ALA–red light, ALA–red light–CAP, and ALA-CAP–red light) against conventional ALA-PDT using visual, histological, and molecular assessments of the affected skin. Results: The results demonstrated that combined treatments strongly inhibited the growth of UV-B-induced skin lesions. TUNEL staining revealed increased apoptosis following both single and combined therapies, while Ki-67 staining indicated reduced keratinocyte proliferation and diminished DNA damage in treated areas. mRNA expression analysis showed the upregulation of apoptosis-related genes (p16^INK4a, p21^CIP1) alongside enhanced anti-tumor immune responses (IL-6, IL-8) in the affected tissue samples. Notably, the combined treatment enhances the therapeutic effect, whereas the sequence of application does not seem to be relevant for therapeutic efficacy in vivo. Conclusions: Overall, these results suggest that CAP may enhance the anti-tumor effect of conventional ALA-PDT, supporting previous findings on SCC cells. Full article

Background and Objectives: Chronic pain is a significant global health issue, with conventional treatment strategies often proving insufficient or causing undesirable side effects. Interventional pain management techniques, including neuromodulation, have gained increasing interest as alternative therapeutic options. Cryoneurolysis, a technique leveraging extreme cold to modulate pain pathways, has emerged as a promising tool in chronic pain management. However, its efficacy and role within current clinical practice remain under evaluation. Methods: A narrative review was conducted by searching PubMed, Scopus, Embase, and Web of Science databases for studies published between 2010 and 2024 using the keywords “Cryoneurolysis”, “Cryoanalgesia”, “Cryoablation”, and “Chronic pain.” Only English-language studies were included. Studies that examined intraoperative cryoablation or lacked statistical analyses (except case reports) were excluded. Results: A total of 55 studies were included: 4 randomized controlled trials (RCTs), 16 retrospective studies, 4 prospective observational studies, and 31 case reports or small case series. The studies displayed significant heterogeneity in patient selection, targeted nerves, procedural protocols, and follow-up durations. While two RCTs demonstrated a significant pain reduction compared to control groups, other RCTs reported no significant improvement. Observational studies and case reports frequently report positive outcomes, with some achieving complete pain relief. Cryoneurolysis appears to be most effective in treating neuropathic pain, particularly in patients with peripheral nerve involvement. Conclusions: Cryoneurolysis is a safe technique for chronic pain management, which has been successfully applied, particularly for selected neuropathic pain conditions. However, the current evidence is limited by study heterogeneity and a lack of high-quality comparative trials. Further well-designed randomized studies are necessary to define its long-term efficacy and its potential role relative to other interventional pain therapies, such as radiofrequency ablation. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) is a painful condition recalcitrant to current available therapies. CIPN pain can be severe and dose-limiting or dose-reducing for life-extending chemotherapeutics and, to date, there is no treatment to alter the progression of CIPN. For these experiments we used docetaxel, a first-line therapy for metastatic prostate cancer in humans and investigated the soluble epoxide hydrolase inhibitor EC5026 for its analgesic efficacy against this CIPN pain. Male SD rats (n = 10/group) were pretreated with 1 mg/kg EC5026 in formulated drinking water or vehicle for one week prior to docetaxel injections. The rats continued the formulated drinking water during three once-a-week docetaxel 10 mg/kg i.p. injections and were maintained on treatment until the end of week 5 when all groups were transitioned to normal drinking water. Nociceptive testing occurred throughout the entire experiment including after transitioning to normal drinking water. EC5026 increased mechanical withdrawal thresholds and latencies on the cold plate compared to docetaxel-treated controls. There were no motor effects of the compound, and the formulated drinking water provided favorable exposure. These results demonstrated that EC5026 administered prophylactically was both analgesic and able to limit the severity of mechanical and cold sensitivities in the docetaxel CIPN rat model. Full article

Background and Objectives: The common cold (acute rhinopharyngitis) and acute rhinosinusitis are highly prevalent conditions that significantly impact quality of life, often leading to nasal congestion, inflammation, and discomfort. Given the growing demand for non-pharmacological treatment options, particularly for vulnerable populations such as children and pregnant women, alternative therapies are increasingly being explored. NESOSPRAY HE-C, a nasal spray formulated with a glycerol-based filmogenic solution, acts by forming a protective osmotic film on the nasal mucosa. This mechanism facilitates mechanical cleansing, enhances decongestion, and reduces inflammation while preserving mucosal integrity. Its purely topical and mechanical mode of action provides a non-systemic alternative for symptom management. Materials and Methods: This randomized, double-blind, parallel-group clinical trial evaluated the efficacy and safety of NESOSPRAY HE-C (n = 29) compared to a placebo nasal spray (n = 26) in patients aged ≥ 3 years diagnosed with the common cold or acute rhinosinusitis. Participants had a baseline Rhinosinusitis Symptom Severity Score (RSSS) of ≥25/50. Treatment consisted of administering 2–3 sprays per nostril, four times daily, every 4 to 6 h, for up to 8 days or until symptom resolution. The primary outcomes included changes in total RSSS, Wisconsin Upper Respiratory Symptom Survey (WURSS) score, and individual symptom scores (rhinorrhea, nasal congestion, cough, poor sleep, facial pain, and fever). Safety assessments included adverse event monitoring and treatment tolerability, with subgroup analyses performed for children and pregnant women. Results: Baseline demographics were comparable between the treatment groups. NESOSPRAY HE-C demonstrated a significantly greater reduction in total RSSS from Day 3 onward (p = 0.0008), with sustained superiority through Day 8 (p < 0.0001). Significant improvements in rhinorrhea and nasal congestion were observed within 2 h of administration (p = 0.0089), while reductions in cough (p = 0.0052), poor sleep (p = 0.0005), and facial pain (p = 0.0111) emerged by Day 3. Fever reduction was most pronounced on Days 6 (p = 0.0001) and 8 (p = 0.0312), indicating a delayed but significant effect. In terms of the WURSS score, NESOSPRAY HE-C showed a significant improvement from Day 1, with a greater reduction in symptom severity compared to placebo. This trend of greater improvement continued through Day 8. The treatment was well tolerated, with no reports of serious adverse events or allergic reactions. Efficacy was consistent across all subgroups, including children, pregnant women, and adults. Conclusions: NESOSPRAY HE-C provides rapid and sustained symptom relief for the common cold and acute rhinosinusitis, serving as a safe and effective non-pharmacological alternative to conventional treatments. By leveraging its osmotic action and barrier-forming properties, it facilitates mechanical cleansing, enhances decongestion, and reduces inflammation while preserving mucosal integrity. Additionally, by forming a protective film on the nasal mucosa, it protects against future irritations, further supporting its role as a valuable therapeutic option, particularly for individuals seeking non-systemic symptom management. Full article

Background: Thermal ablation of centrally located liver tumors carries an increased risk of bile duct injury due to their proximity to the biliary tree. We aim to evaluate whether biliary cooling using a nasobiliary tube can effectively mitigate bile duct injury during the ablation process. Methods: We retrospectively analyzed the data of 322 patients who underwent thermal ablation at Dalin Tzu Chi Hospital from July 2020 to June 2023 and identified those who received prophylactic biliary cooling during thermal ablation for central liver tumors. Data including demographics, tumor characteristics, procedural details, and clinical outcomes were analyzed. Results: Among the 322 patients who underwent thermal ablation, 9 with central liver tumors received prophylactic biliary cooling. The median distance between the tumor and the central bile duct was 1 mm (range: 0–4 mm), the temperature of the cold normal saline was 4 °C, and the mean volume of normal saline infused was 150 mL (range: 100–200 mL). Complete ablation was achieved in all patients in a single session without any biliary injury. One patient developed acute cholangitis after ENBD placement, which resolved with antibiotic therapy. Conclusions: Biliary cooling with 4 °C cold saline through a nasobiliary tube can improve the safety and effectiveness of thermal ablation for central liver tumors. Full article

Advanced prostate cancer (PCa) remains lethal despite standard therapies, and immune checkpoint inhibitors offer limited benefit in its “immune-cold” microenvironment. T-cell engagers (TCEs)—bispecific antibodies linking CD3 on T-cells to tumor-associated antigens (TAAs)—provide potent, MHC-independent cytotoxicity, overcoming a key resistance mechanism. While early PSMA-targeted TCEs established proof-of-concept, recent data, notably for six transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeting agents like Xaluritamig, demonstrate more substantial objective responses, highlighting progress through improved target selection and molecular design. This review synthesizes the evolving landscape of TCEs targeting PSMA, STEAP1, and DLL3 in PCa. We critically evaluate emerging clinical evidence, arguing that realizing the significant therapeutic potential of TCEs requires overcoming key challenges, including cytokine release syndrome (CRS), limited response durability, and antigen escape. We contend that future success hinges on sophisticated engineering strategies (e.g., affinity tuning, masking, multispecific constructs) and rationally designed combination therapies tailored to disease-specific hurdles. Strategies for toxicity mitigation, the crucial role of biomarker-driven patient selection, and potential integration with existing treatments are also discussed. Accumulating evidence supports TCEs becoming a new therapeutic pillar for advanced PCa, but achieving this demands sustained innovation focused on optimizing efficacy and safety. This review critically connects molecular engineering advancements with clinical realities and future imperatives. Full article