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.

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

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.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

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.

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.

Objective To explore the association between aspartate aminotransferase(AST)/alanine aminotransferase(ALT)ratio and metabolic syndrome(MS)in elderly hypertensive patients,and to provide reference for early detection and prevention of MS in elderly hypertensive patients.Methods A questionnaire survey and physical examination were conducted among 616 elderly hypertensive patients at community health service centers.Participants were divided into two groups based on MS status:MS group(n=334)and non-MS group(n=282).According to AST/ALT levels,participants were divided into four groups:q1 group(AST/ALT ≤0.88,n=156),q2 group(0.88＜AST/ALT ≤ 1.10,n=155),q3 group(1.10＜AST/ALT ≤ 1.37,n=154),and q4 group(AST/ALT＞1.37,n=151).Blood biochemical parameters including triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),AST,ALT,and blood glucose were measured.The impact of AST/ALT levels on MS was analyzed using a Logistic regression model,while the risk prediction for MS occurrence was evaluated through receiver operating characteristic(ROC)curves.Results MS group showed higher body mass index(BMI),TG,ALT levels,abnormal glucose levels,female proportion,and abdominal obesity rate compared to non-MS group.HDL-C and AST/ALT values of MS group were lower than those in non-MS patients(P＜0.05).Logistic regression analysis revealed that after adjusting for BMI,smoking,alcohol consumption,physical activity,education level,marital status,TG,HDL-C,and glucose levels,both q3 and q4 groups demonstrated reduced MS risk compared to group q1 group(P＜0.05).ROC curve analysis indicated that the area under the curve for AST/ALT in MS was 0.638(P＜0.05).Conclusion The level of AST/ALT was negatively correlated with MS in elderly hypertensive patients,and AST/ALT has certain predictive value for the risk of MS in elderly hypertensive patients.

Objective:To investigate the mechanism by which histone deacetylase 6 (HDAC6) exerts immune protective effects in Chlamydia trachomatis respiratory tract infection. Methods:Wild-type (WT) C57BL/6 mice and HDAC6 gene knockout (HDAC6 -/-) mice were used to establish mouse models of Chlamydia muridarum ( Cm) respiratory infection by nasal inhalation of Cm. qPCR and Western blot were used to detect the relative expression of HDAC6 in lung tissues of WT mice after Cm infection. Intracellular factor staining was used to detect the percentages and absolute numbers of CD4 + T cell subsets (Th1, Th17 and Th2 cells)in mouse lung tissues after infection. The levels of IL-4 in spleen cell culture supernatants were measured by ELISA. One-way or two-way analysis of variance (ANOVA) was used for statistical analysis. Results:Cm respiratory tract infection significantly promoted the expression of HDAC6 at both mRNA and protein levels in lung tissues of WT mice ( P<0.001). HDAC6 -/- mice lost more weight than WT mice and took longer to recover to the normal level. Chlamydia load ( P<0.001 and P<0.05) and pathological damage ( P<0.05 and P<0.000 1) in lung tissues were more serious in HDAC6 -/- mice than in WT mice at 7 and 14 d after infection. Neither the percentage nor the absolute number of Th1 (CD4 + IFN-γ + T) and Th17 (CD4 + IL-17 + T) cells showed significant differences between WT and HDAC6 -/- mice, while the percentage and absolute number of Th2 (CD4 + IL-4 + T) cells increased in HDAC6 -/- mice ( P<0.05 and P<0.01). Moreover, in HDAC6 -/- mice, the expression of IL-4 mRNA increased ( P<0.000 1) and the level of IL-4 in the splenic cell culture supernatants increased ( P<0.01). Conclusions:HDAC6 plays an immune protective role in Cm infection. It can reduce the susceptibility of host to Cm respiratory tract infection and alleviates the pathological damage in lung tissues by inhibiting the immune response of Th2 cells.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.