Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Cancer stem cells (CSCs) represent a distinct subpopulation of cells characterized by self-renewal capacity, differentiation potential, and critical roles in driving tumor progression, therapeutic resistance, recurrence, and maintenance of the tumor microenvironment. Targeting CSCs has emerged as a pivotal direction in cancer research, offering novel strategies to overcome drug resistance and prevent metastasis and relapse. Lysosomes, traditionally recognized as central organelles for intracellular degradation and recycling, are indispensable for cellular homeostasis. Dysregulation of lysosomal function is intimately linked to various diseases, including cancer. In tumors, aberrant lysosomal activity can promote malignant progression through mechanisms such as altering metabolic pathways, enhancing lysosomal exocytosis, modulating drug resistance, and interfering with autophagy-lysosomal pathways. Recent studies have underscored the involvement of lysosomes in regulating CSC properties. This review synthesizes findings on lysosomal regulation of CSCs through the following aspects. (1) Lysosomes exert complex and critical bidirectional control over CSC stemness maintenance through three degradation pathways that are dependent on their degradative function. (i) The lysophagy pathway. This pathway exhibits dual roles. Activation can sustain CSC functions; for instance, in glioblastoma, hypoxia upregulates Gal-8 via the STAT3/HIF1α signaling axis to induce autophagy, supporting stem cell survival. In head and neck squamous cell carcinoma, degradation of GSK3β activates the Wnt pathway, enhancing stemness. Conversely, this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A, thereby impairing CSC self-renewal capacity. (ii) Mitophagy pathway. In non-small cell lung cancer stem cells, mitophagy-related mechanisms, such as the accumulation of mitochondrial DNA (mtDNA) activating the TLR9-Notch1-AMPK signaling axis, have been shown to promote CSC proliferation. (iii) Autophagosome-dependent lysosomal degradation pathway. This pathway directly regulates stemness-related proteins in a bidirectional manner. Enhanced degradative function can promote CSC properties, exemplified by the degradation of NUMB to activate Notch signaling. Conversely, attenuated degradative function can also enhance stemness by stabilizing oncoproteins (e.g., protecting Frizzled-1 from degradation to sustain Wnt signaling) or preventing the degradation of tumor suppressors (e.g., inhibiting Notch degradation). (2) Constituent proteins of lysosomes, including membrane proteins and luminal acid hydrolases, participate in regulating CSC stemness. Regarding membrane proteins, LAMP2A facilitates chaperone-mediated autophagy to maintain stemness in glioblastoma and ovarian cancer. V-ATPase, by maintaining an acidic luminal environment, promotes proliferation and drug resistance in glioma stem cells. Among hydrolases, cathepsins B and L are highly expressed in pancreatic and ovarian cancers and correlate with poor prognosis. Furthermore, targeting lysosomes to induce lysosomal membrane permeabilization (LMP) triggers lysosome-mediated cell death, presenting a potential therapeutic strategy for eradicating CSCs.(3) The acidic luminal environment, single-membrane structure, and the presence of transmembrane transporters (e.g., ABCA3) enable lysosomes to passively trap or actively uptake and sequester chemotherapeutic drugs. Subsequent drug extrusion via exocytosis confers drug resistance. In CSCs, this lysosome-mediated drug sequestration, often cooperating with autophagy, establishes multimodal drug resistance. Therefore, targeting lysosomal function represents a potential strategy to overcome therapy resistance. The central role of lysosomes in regulating CSC stemness and resistance positions them as highly promising therapeutic targets. Strategies aimed at disrupting lysosomal function to selectively eliminate CSCs include: inhibiting the lysosome-autophagy system using agents like IITZ or lovastatin; inducing lysosomal membrane permeabilization (LMP) with compounds such as hexamethylene amiloride to compromise membrane stability; and disrupting the acidic luminal environment using drugs like siramesine or the K/H transport compound 2. In conclusion, lysosomes critically regulate CSC stemness maintenance and drug resistance through degradative pathways, membrane protein functions, luminal hydrolase activities, and drug sequestration mechanisms. This redefines the lysosome from a traditional “waste disposal unit” to a “signal integration center” in CSCs. The duality and context-dependency of lysosomal function in CSCs offer novel insights into the heterogeneity observed across different tumors. Targeting lysosomal vulnerabilities—such as inducing LMP, disrupting acidity, or blocking autophagic flux—provides a strategy to bypass canonical CSC resistance mechanisms and directly trigger cell death. This establishes the lysosome as a key target to overcome CSC-mediated therapy resistance, paving the way for developing diverse candidate drugs and innovative combination therapies in oncology.

Robotic-assisted pedicle screw placement and full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) are established minimally invasive spine techniques. Their integration has the potential to combine navigation accuracy with the muscle-preserving advantages of uniportal endoscopy. This technical note describes a hybrid approach using the Mazor X Stealth edition robotic system to enhance workflow, safety, and efficiency during FE-TLIF. A 74-year-old patient with metabolic syndrome presented with severe back and radicular leg pain that was refractory to conservative treatment. Magnetic resonance imaging demonstrated bilateral lateral recess stenosis, disc height loss, and facet arthropathy at L4–5, with dynamic instability observed on flexion-extension radiographs. Preoperative computed tomography imaging was uploaded to the robotic system for trajectory planning. Following registration, the robotic arm guided percutaneous pedicle screw placement via Wiltse incisions. Uniportal endoscopic access enabled hemilaminotomy, facetectomy, discectomy, endplate preparation, and insertion of an expandable L4–5 interbody cage under direct visualization. Robotic guidance facilitated precise screw trajectory placement without repeated fluoroscopic localization, reduced intraoperative radiation exposure, and avoided muscle disruption associated with open approaches. Endoscopic visualization enabled controlled facet resection and preservation of neural elements during cage placement. Postoperative radiographs confirmed appropriate implant positioning. The combined workflow improved surgical ergonomics and minimized tissue trauma while maintaining fusion stability. Robotic-assisted FE-TLIF represents a safe and feasible hybrid minimally invasive surgery technique that enhances pedicle screw accuracy and complements endoscopic fusion. Despite a steep learning curve, this approach may reduce perioperative morbidity, improve procedural efficiency, and enhance postoperative recovery. Further comparative studies are required to evaluate long-term clinical and radiographic outcomes.

Introduction: Accurate diagnosis of thyrotoxicosis, a condition resulting from excessive thyroid hormone activity, is essential for appropriate management. However, access to diagnostic tools such as thyrotropin receptor antibody (TRAb) assays and thyroid ultrasonography remains limited in resource-constrained settings, highlighting the need for cost-effective alternatives. Recent studies suggest that the free triiodothyronine to free thyroxine (FT3/FT4) ratio may serve as a potential biomarker for differentiating the causes of thyrotoxicosis. Methodology: This cross-sectional study evaluated the FT3/FT4 ratio in newly diagnosed thyrotoxicosis patients aged ≥18 years recruited from Hospital Tengku Ampuan Rahimah, Hospital Banting, Klinik Kesihatan Pelabuhan Klang, and Klinik Kesihatan Pandamaran between February and December 2025. All participants underwent thyroid function testing (FT3, FT4, and TSH) and autoantibody assessment (TRAb and anti-thyroid peroxidase [anti-TPO]). Diagnostic performance of the FT3/FT4 ratio for Graves’ disease was assessed using receiver operating characteristic (ROC) curve analysis. Results: Fifty-eight patients were included, of whom 58.6% were diagnosed with Graves’ disease. Patients with Graves’ disease had significantly higher FT3 levels (median 16.8 pmol/L; IQR 10.9–25.7) compared to those with non-Graves’ thyrotoxicosis (median 8.3 pmol/L; IQR 5.3–13.5; p <0.001), with similar trends observed for FT4 levels (p <0.001). However, the FT3/ FT4 ratio did not differ significantly between groups (p >0.05), with an overall ROC AUC of 0.572, indicating poor discriminatory ability. Subgroup analysis based on FT4 levels improved performance; at FT4 <30 pmol/L, the FT3/FT4 ratio demonstrated 75.0% sensitivity, 91.7% specificity, and 87.5% diagnostic accuracy at a cutoff of 0.3445 (AUC = 0.813; 95% CI: 0.570–1.000; p = 0.069). No significant association was observed between the FT3/FT4 ratio and TRAb or anti-TPO. Conclusion The FT3/FT4 ratio has limited overall diagnostic utility but may provide adjunctive value in selected biochemical contexts, particularly in settings with limited access to immunological testing.
Diagnosis, Differential ; Thyroxine ; Triiodothyronine ; Thyrotoxicosis ; Cross-Sectional Studies

Muscle-invasive bladder cancer (MIBC) is an aggressive cancer with a high recurrence risk due to micrometastases. Standard treatment, neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy, is not suitable for all patients, with many being ineligible or experiencing recurrence, alongside significant toxicity concerns.Current Concepts: The introduction of immune checkpoint inhibitors (ICIs) into the perioperative setting —including neoadjuvant ICI use in cisplatin-ineligible patients, adjuvant ICI use in high-risk individuals, and chemoimmunotherapy in either the preoperative or postoperative period—has demonstrated promising clinical outcomes. Additionally, bladder preservation strategies are currently under investigation in select patients who exhibit favorable treatment responses, aiming to maintain quality of life without compromising oncologic outcomes. Nevertheless, challenges such as overtreatment, long-term toxicity, and immune-related adverse events remain significant, underscoring the necessity for precise patient selection.Discussion and Conclusion: To personalize perioperative management of MIBC, it is essential to develop and clinically implement robust predictive biomarkers. Assessment of molecular residual disease using circulating tumor DNA is emerging as a promising method to stratify risk, guide adjuvant treatment decisions, and monitor therapeutic response in real time. Future research should prioritize the validation of these biomarkers, refinement of patient selection criteria for bladder preservation strategies, and evaluation of novel therapeutic agents such as antibody-drug conjugates and fibroblast growth factor receptor inhibitors in the perioperative setting. Ultimately, adopting a precision oncology approach will be critical for balancing oncologic efficacy with toxicity management and achieving patient-centered outcomes.

Objectives: Hip fracture is a global public concern exhibiting high mortality rates but often underrecognized. We compared the mortality rates, risk, and secular trend of hip fractures with common cancers in females and males, aiming to call attention to hip fractures. Methods: In 2010–2020, 193,767 patients with the first diagnosed hip fractures and the top 5 prevalent cancers in each sex and aged 50 years and above were included. Age-standardized mortality rates were adjusted to the WHO Standard Population and the sex-specific relative risk of mortality was computed using Cox proportional hazards models, adjusted for potential confounders. The trend analyses used joinpoint regression to compute annual percent changes in age-standardized mortality rates. Results The 1-year and 5-year age-standardized mortality rates and sex-specific mortality risk of hip fracture are greater than those of breast cancer (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90 to 0.97) and thyroid cancer (HR: 0.55, 95% CI: 0.47 to 0.64) in females and prostate cancer (HR: 0.56, 95% CI: 0.53 to 0.58) in males. Moreover, mortality rates in lung cancer, male liver cancer, female breast cancer, and male prostate cancer have decreased in the past decade. For hip fracture, the mortality rates have significantly decreased in females, while in males, we observed only a decreasing trend in 1-year hip fracture mortality, not in 5-year Conclusions: Hip fractures exhibit higher mortality compared to female breast and thyroid cancers and male prostate cancer. More attention is needed to enhance the management and prevention of hip fractures.

Objective:To strengthen the management of low-value consumables in public hospitals by introducing the Supply Processing Distribution(SPD)management model,and to explore refined operational management strategies and path optimization for low-value consumables.Methods:The SPD management model was introduced,and the entire process of hospital consumables was refinedly managed using third-party supply chain information management platforms,visualized tertiary department warehouses,Radio Frequency Identification(RFID)technology and intelligent cabinet systems,Unique Device Identification(UDI)coding,"four-code integration"and other supporting technologies.Results:Based on the analysis of the current situation in the target Hospital,specific measures related to the management of low-value consumables were introduced after the introduction of the SPD model.Conclusion:It provides a reference and guidance for the hospital's medical consumables management department to promote refined management of medical consumables under the SPD model.

Aim To investigate the mechanism of 8-hydroxygenistein(8-OHG)in mitigating high-altitude induced heart injury(HAHI)via network pharmacolo-gy,molecular docking and animal experiment.Meth-ods 8-OHG-related targets were obtained from Swis-sTargetPrediction,Similarity ensemble approach,Su-perPred and PharmMapper databases.Genecards and OMIM databases were utilized for retrieving HAHI-re-lated targets.Venn diagram was drawn using R pack-age.STRING 11.5 and Cytoscape 3.9.1 were used to construct the protein-protein interaction network and screen core targets.GO and KEGG enrichment analysis were carried out using DAVID database.AutoDock Vi-na software was used for molecular docking.Visualiza-tion was performed using PyMOL 3.0.0 software.The HAHI model was established,and the the mice were randomly divided into the control group,model group and 8-OHG group.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of myo-cardial tissue.Western blot was applied for detecting the expression levels of related proteins in myocardial tissue.Results A total of 73 overlapping targets be-tween 8-OHG and HAHI were screened,with ALB,AKT1,ESR1,HSP90AA1,NFKB1 and MMP9 were regarded as core targets.Molecular docking results in-dicated that 8-OHG had strong binding ability with these core targets.GO functional enrichment analysis obtained 185 biological processes,including negative regulation of apoptosis,response to hypoxia and in-flammatory response,38 cell compositions,including cytosol,cytoplasm,plasma membrane,as well as 71 molecular functions,including protein binding,metal ion binding,enzyme binding and so on.Altogether 55 signaling pathways were identified via KEGG enrich-ment analysis,including PI3 K/Akt signaling pathway,HIF-1 signaling pathway and MAPK signaling pathway.The results of animal experiments showed that 8-OHG could significantly improve the myocardial histopatho-logical change induced by high-altitude hypoxia expo-sure.Western blot results showed that compared with the normal group,the ratio of p-PI3K/PI3K and p-Akt/Akt in the myocardial tissue of mice in the model group significantly decreased,while the protein expres-sion of Beclin-1 and the ratio of LC3B-Ⅱ/LC3B-Ⅰsignificantly increased,while 8-OHG could reverse these changes.Conclusion The mechanism of 8-OHG in alleviating HAHI is related to its activation of PI3K/Akt signaling pathway,thereby inhibiting auto-phagy induced by high-altitude hypoxia exposure.

Objective:To investigate the effects of radiofrequency technology combined with electrical stimulation biofeedback training on stress urinary incontinence in female patients.Methods:This is a prospective study that included 360 female patients with stress urinary incontinence who visited the Department of Gynecology and Obstetrics at Lianyungang Maternal and Child Health Hospital from June 2021 to June 2023. The patients were divided into three groups using a random number table method: a radiofrequency treatment group ( n = 120, treated with radiofrequency technology), an electrical stimulation treatment group ( n = 120, treated with electrical stimulation biofeedback training), and a combined treatment group ( n = 120, treated with a combination of radiofrequency technology and electrical stimulation biofeedback training). The clinical efficacy of the three groups was evaluated. Before and after treatment, a 1-hour pad test and urine test were conducted. The Incontinence Questionnaire-Urinary Incontinence Short Form was used to assess the surface electromyography values of the pelvic floor muscles in patients across the three groups. Results:The effective treatment rate in the combined treatment group was 87.50% (105/120), which was significantly higher than the rates in the radiofrequency treatment group (69.17%, 83/120) and the electrical stimulation treatment group (71.67%, 86/120) ( χ2 = 13.05, P < 0.05). After treatment, the 1-hour pad test showed that the urine leakage amounts and the Incontinence Questionnaire-Urinary Incontinence Short Form scores for the combined treatment group were (1.14 ± 0.16) g and (4.15 ± 0.48), respectively. In comparison, the values in the radiofrequency treatment group were (3.04 ± 0.42) g and (8.66 ± 0.89), while in the electrical stimulation treatment group they were (3.01 ± 0.39) g and (8.78 ± 0.91). Differences among the three groups were statistically significant ( F = 1 024.37, 1 354.96, all P < 0.05). After treatment, the surface electromyography values during the rapid contraction, sustained contraction, and endurance contraction phases for the combined treatment group were (31.97 ± 3.24) μV, (27.01 ± 3.02) μV, and (20.05 ± 2.11) μV, respectively. For the radiofrequency treatment group, the values were (27.85 ± 2.72) μV, (21.63 ± 2.39) μV, and (15.14 ± 1.63) μV, while the electrical stimulation treatment group showed values of (27.93 ± 2.75) μV, (22.04 ± 2.41) μV, and (15.39 ± 1.67) μV. Differences among the three groups were also statistically significant ( F = 78.49, 156.43, 278.16, all P < 0.05). Conclusions:Radiofrequency technology combined with electrical stimulation biofeedback training can substantially improve pelvic floor muscle strength and reduce urinary incontinence symptoms in female patients with stress urinary incontinence.

Objective To investigate the effects of synovial fluid from patients with rheumatoid arthritis(RA)on the polarization of normal neutrophils and the MEK/ERK signaling pathway,thereby providing experimental evidence to elucidate the pathological mechanisms of RA and offering novel insights into its treatment.Methods Synovial fluid samples were collected from 20 RA patients and 20 osteoarthritis(OA)patients.ELISA was used to measure the levels of interferon-gamma(IFN-γ),tumor necrosis factor-alpha(TNF-α),transforming growth factor-beta(TGF-β)and interleukin-8(IL-8)in the synovial fluid.Neutrophils were isolated from the peripheral blood of healthy donors,and their purity was confirmed by flow cytometry.Neutrophils were then treated with synovial fluid and divided into four groups:Control(untreated),RA(treated with 10％RA synovial fluid),OA(treated with 10％OA synovial fluid),and anti-IFN-β(treated with 20 μg anti-IFN-β antibody as an N2-type control).Western blot was used to assess the changes in the expression of IFN-γ,TNF-α,TGF-β,MEK,p-MEK,ERK and p-ERK.Additionally,the MEK inhibitor PD0325901 was used to block the MEK/ERK pathway,and subsequent changes in IFN-γ and TGF-β expression in neutrophils were evaluated.Results The levels of IFN-γ,TNF-α,TGF-β and IL-8 in the synovial fluid of RA patients were significantly higher than those in OA patients.After intervention with RA synovial fluid,the relative expression of IFN-γ and TNF-α in neutrophils were significantly increased compared to those in the untreated control group and the OA group.While,TGF-β expression in the RA group was lower than that in both the control and anti-IFN-β groups.The relative expression of p-MEK and p-ERK in the RA group were significantly higher than those in the control,OA and Anti-IFN-β groups.Upon addition of the MEK inhibitor,the relative expression of p-MEK and p-ERK were reduced.Furthermore,in both the RA and OA groups,the relative expression levels of IFN-γ decreased,while the expression of TGF-β increased.Conclusion Synovial fluid from RA patients contains higher of IFN-γ,TNF-αand TGF-β,which activate neutrophils through phosphorylation of the MEK/ERK signaling pathway,promoting their polarization toward the pro-inflammatory N1 phenotype.