Thrombocytopenia remains a formidable clinical challenge across a broad spectrum of medical conditions, as it substantially elevates hemorrhagic risk and complicates established therapeutic protocols. Although platelet transfusions have traditionally served as the cornerstone of management, their utility is frequently constrained by transient efficacy and inherent logistical burdens. The emergence of thrombopoietic agents, particularly second-generation thrombopoietin receptor agonists (TPO-RAs), has shifted the treatment landscape by offering a more direct and targeted way to stimulate platelet production. This review evaluates the mechanisms and clinical utility of contemporary therapies, spanning from recombinant human thrombopoietin (rhTPO) and established TPO-RAs (eltrombopag, romiplostim, and herombopag) to emerging classes such as spleen tyrosine kinase (SYK) and Bruton tyrosine kinase (BTK) inhibitors. We delineate their specific roles in the management of immune thrombocytopenia (ITP), chemotherapy-induced thrombocytopenia (CIT), chronic liver disease (CLD), and aplastic anemia (AA). Despite these advancements, challenges including inconsistent response rates, long-term safety considerations, and accessibility barriers persist. Looking ahead, the field is pivoting toward personalized management strategies and next-generation agents to further refine patient care and optimize clinical outcomes.
Immune-mediated inflammatory diseases (IMIDs), including psoriasis, lupus, multiple sclerosis, and inflammatory bowel disease, are chronic conditions characterized by immune dysregulation and excessive inflammatory cytokine expression. Biologic therapies have transformed IMID management, and the introduction of biosimilars has improved treatment accessibility by reducing costs and alleviating the burden on healthcare systems. Despite regulatory approval and demonstration of similarity to reference biologics, biosimilar adoption remains limited due to uncertainties regarding interchangeability and extrapolation, insufficient communication among stakeholders, and the nocebo effect that influences patient and physician confidence. Although regulatory agencies provide detailed guidance and European Public Assessment Reports, regulatory and perceptual barriers persist in clinical practice. This work reviews real-world and clinical trial data on switching from reference biologics to biosimilars in IMIDs and demonstrates comparable safety and efficacy outcomes. However, patient perceptions and communication strategies significantly influence treatment success. Despite the available evidence, negative perceptions and a lack of confidence persist among both patients and healthcare professionals. Promoting understanding and confidence in biosimilars can increase access and availability and, consequently, enhance the benefits associated with their wider use. Therefore, addressing educational, regulatory, and clinical practice gaps is essential for optimizing biosimilar integration in IMID management.
Bone morphogenetic proteins (BMPs) are bone-derived osteokines that regulate energy metabolism and combat obesity by promoting brown adipocyte differentiation. BMP4, BMP7, BMP8B, and BMP9 are highly expressed in osteoblasts and bone matrix, from which they are released into circulation. They act as endocrine factors that induce brown adipogenesis, increase mitochondrial biogenesis, and increase thermogenesis via conserved signaling pathways (Smad, MAPK, and PGC1α). Concurrently, these BMPs maintain skeletal homeostasis and mediate crosstalk between bone and metabolic organs, including adipose tissue and the hypothalamus, thereby regulating appetite and energy balance. Preclinical studies have confirmed that BMP-based interventions can increase energy expenditure, improve insulin sensitivity, and alleviate obesity-related complications. However, clinical translation remains hindered by adverse effects, short half-lives, and obesity-induced BMP resistance. This review first elucidates the peripheral and central regulatory mechanisms of BMPs in energy metabolism, clarifies the subtype-specific metabolic effects of major BMPs, further evaluates their therapeutic potential against obesity and metabolic syndrome, and finally analyzes the core obstacles to clinical implementation and corresponding solution strategies.
Romiplostim, a second‑generation thrombopoietin receptor agonist (TPO‑RA), has been increasingly investigated for aplastic anemia (AA) across various populations and treatment settings; however, its overall efficacy, optimal dose, safety profile, and sources of heterogeneity across studies have not been systematically quantified and validated. This study aims to perform an up‑to‑date systematic review and single‑arm meta‑analysis to comprehensively assess the overall efficacy and safety of romiplostim in AA patients.
We systematically searched PubMed, Embase, Web of Science, Cochrane Library, and CNKI from inception to March 3, 2026, without language restrictions. Two independent reviewers screened literature, extracted data, and assessed methodological quality using the Newcastle–Ottawa Scale (NOS) and Methodological Index for Non-Randomized Studies (MINORS). A random-effects model was applied in Stata 15.1 to pool overall response rate (ORR) and complete response rate (CRR); subgroup, sensitivity, and publication bias analyses were performed to explore heterogeneity and robustness.
Nineteen studies with 382 patients were included. The pooled ORR was 72.4% (95% CI: 61.9%–81.9%), and CRR was 25.5% (95% CI: 18.4%–33.1%). Patients receiving 20 μg/kg romiplostim achieved higher ORR (77.6% vs. 51.7%) and CRR (29.3% vs. 17.0%) than those receiving 10 μg/kg (P = 0.081). Patients aged <60 years showed higher ORR (74.9% vs. 49.3%) than those ≥60 years (P = 0.298). Tolerability was favorable, with low discontinuation rate (2.1%) and no treatment-related deaths.
Romiplostim demonstrates promising efficacy and safety in AA, with enhanced outcomes at 20 μg/kg and in younger patients. Further high-quality trials are warranted.
The peptide-loading complex (PLC) is a pivotal endoplasmic reticulum (ER) protein machinery that facilitates peptide translocation, editing, and loading onto major histocompatibility complex class I (MHC-I) to allow recognition of infected or transformed cells by CD8⁺ cytotoxic T lymphocytes (CTLs). PLC comprises the peptide transporter complex formed of transporters associated with antigen processing (TAP1/2), the adapter protein tapasin, chaperones such as calreticulin (CRT) and ERp57, and β2-microglobulin (β2M), ensuring the proper assembly of MHC-I/peptide complexes for subsequent antigen presentation on the cell surface. In cancer, tumorigenesis often involves structural malfunctions and transcriptional, post-transcriptional, and epigenetic modifications that impair the functioning of PLC proteins. This eventually causes loss of MHC-I cell-surface expression, failure of antigen presentation, and escape from CTL-mediated immunosurveillance. Although malfunctions in antigen-processing machineries are well known, herein we provide an overview of the PLC as a major determinant of tumor immune escape and a potential therapy target. In this regard, recent evidence indicates that individual PLC components not only affect MHC-I/antigen presentation but also influence tumor development and progression, immune evasion, and treatment resistance. Furthermore, we explore existing or evolving therapeutic approaches to recover/reprogram PLC functions such as IFN-γ-induced PLC activation, TAP1 and tapasin gene therapy, epigenetics-based treatments such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), and microRNA targeting strategy.
Parkinson’s disease (PD) is the most prevalent neurodegenerative movement condition. Tremors, stiffness, bradykinesia/akinesia, and postural instability are its primary motor symptoms; nevertheless, the clinical features also include non-motor and additional motor symptoms. Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is present in several human tissues and performs a range of cell-dependent regulatory actions. Various neurological diseases, such as PD, Alzheimer’s disease (AD), and Huntington’s disease (HD), have been linked to KLF4, which regulates some neurophysiological and neuropathological processes in the brain. Recent data indicate that KLF4 plays a crucial regulatory role in the neurophysiological and neuropathological processes underlying PD, suggesting that it might be a viable therapeutic target for neurodegenerative diseases. This review focuses on the potential molecular mechanism underlying KLF4-mediated neuroinflammation, oxidative stress, mitochondrial dysfunction, and apoptosis. KLF4-mediated pathways are clarified by the information gathered here, and targeting them appears to be a viable therapeutic strategy for treating PD. Nevertheless, there is insufficient information on this subject, and more investigations are needed to fully understand the translational significance of the KLF4-oriented therapeutic strategy in PD.
Neuromodulation technology, an interdisciplinary field integrating neuroscience, engineering, and clinical medicine, offers novel therapeutic paradigms for numerous intractable diseases. In pain medicine, it modulates nervous system function through electrical or chemical signals, emerging as a core approach for managing refractory pain. However, the rapid advancement of this technology has coincided with a persistent underappreciation of the core value and multidimensional roles of pain physicians. This paper systematically elucidates the essence and scope of neuromodulation technology, analyzes its unique advantages in addressing the diagnostic and therapeutic challenges of refractory pain, and reviews its rapid developmental trajectory. It critically highlights the indispensable, yet often underestimated, role of pain physicians in driving the high-quality advancement of this field. Furthermore, this paper explores safety concerns in clinical applications and highlights the need to establish robust monitoring, evaluation, and education systems. Finally, future directions for pain specialists in leading the evolution of neuromodulation are outlined.
Osteoporosis is typically characterized by reduced bone mass and deterioration of microarchitecture. However, bone mineral density (BMD) does not fully account for the wide variations in skeletal fragility. In this study, we propose that matrix competence is the capacity of the mineralized extracellular matrix (ECM), the lacunar–canalicular network (LCN), and the osteocyte network to ensure material integrity, maintain network connectivity, and present appropriate cell–matrix adhesion cues. When these properties are degraded, matrix-to-signal breakdown occurs: mechanical and inflammatory inputs are no longer translated efficiently into coordinated remodeling. Research findings on bone material biology, osteocyte regulation, mechanotransduction, and osteoimmunology indicate that load-adaptive formation requires efficient signal amplification and propagation across matrix and cellular networks. During aging and unloading, the properties of collagen–mineral material decrease, LCN and osteocyte coupling decrease, and anabolic adaptation becomes blunted. Chronic low-grade inflammation and immune remodeling can further exploit altered ECM positioning and adhesion, reinforcing resorptive remodeling. We suggest that reduced matrix competence provides a tissue-level explanation for the relationships among BMD, fracture risk, and therapeutic response. This framework places matrix material properties, network structural integrity, and remodeling coordination at the center of osteoporosis phenotyping independent of BMD.
To address the urgent need for non-invasive diagnosis of endometriosis, this study developed a novel microfluidic platform utilizing a three-dimensional (3D) polydimethylsiloxane scaffold microchip to efficiently capture circulating endometrial cells (CECs).
A prospective single-center study was performed from June 2022 to June 2023. Presurgical peripheral blood was collected from 42 patients with endometriosis and 20 controls. Microchips were functionalized with antibodies against epithelial cellular adhesion molecule (EpCAM) and cluster of differentiation 10 (CD10). They were used to capture and identify CECs for diagnostic evaluation.
The presence of CD10 was observed in 88.10% of cases (37/42), significantly higher than in controls (35%, 7/20, P < 0.001). Similarly, the levels of EpCAM were detected in 52.38% of cases (22/42) and 30% of controls (6/20, P = 0.25). In preoperative diagnosis, integrating CECs with clinical parameters achieved superior accuracy (AUC = 0.870) compared to CA125 (AUC = 0.813) and clinical-only models (AUC = 0.606–0.923). When comparing CEC levels before and after surgery, the CEC-integrated clinical model demonstrated robust diagnostic performance (AUC = 0.877).
This 3D microfluidic platform enables precise, convenient, and non-invasive endometriosis identification via efficient CEC capture, offering significant potential for clinical translation.
Hysterectomy significantly increases the risk of pelvic organ prolapse (POP). However, the underlying molecular changes remain unclear. The aim of this study was to elucidate potential molecular associations by comparing single-cell transcriptomic profiles of vaginal tissues from postmenopausal women across three groups: normal controls, POP patients with an intact uterus, and post-hysterectomy POP patients.
A single-cell transcriptomic dataset of prolapsed vaginal tissues was used to analyze genes that were differentially expressed between fibroblasts and macrophages in the two prolapse types. Key transcriptional regulators of myofibroblast differentiation were identified. Cell subtypes were identified, and macrophage polarization states were assessed to evaluate immune responses in different POP subtypes.
Post-hysterectomy POP patients exhibited impaired myofibroblast differentiation, downregulated expression of wound-healing genes, and disrupted extracellular matrix (ECM) remodeling. In contrast, uterus-intact POP patients showed stronger immune activation, enhanced fibroblast‒macrophage crosstalk, and upregulated expression of genes related to leukocyte-mediated immunity. Key transcriptional regulators were linked to myofibroblast differentiation. Macrophage profiling revealed predominant M2 polarization in post-hysterectomy patients, indicating a potential compensatory response to biomechanical instability, whereas uterus-intact POP patients maintained more active immune responses.
This study revealed that hysterectomy alters vaginal homeostasis through ECM disorganization, impaired wound healing, and macrophage reprogramming. Our findings highlight distinct molecular changes in fibroblasts and macrophages between uterus-intact POP patients and post-hysterectomy POP patients, advancing the understanding of POP pathogenesis.
A significant gap exists in medical support for organ transplant patients during out-of-hours (OOH). General large language models (LLMs), affected by AI hallucinations, are unsuitable for complex post-transplant care. We built the first post-transplant AI agent based on LLMs to address these issues.
We constructed a specialized “post-transplant AI agent” (named Doctor Xiao Yi) and conducted a mixed-methods study comparing it to a hospital-wide general AI agent (named Nan Xiao Yi). Data included 20,176 real-world logs (June–December 2025) and a cross-sectional survey of 152 transplant patients. We examined patterns of use over time, the types of questions raised, and the factors influencing patient behavior.
Unlike Nan Xiao Yi, Doctor Xiao Yi remained active during OOH, with a peak at 4:00 AM (P < 0.001). The general agent handled admin tasks like appointments, while the specialist agent provided clinical support such as diet, symptoms, and medication. Survey found 60.5% of OOH use by transplant patients due to reluctance to disturb human doctors. Furthermore, 63.8% of transplant patients were satisfied with the specialist agent's responses, and 48% reported they would decide on further hospital treatment based on AI suggestions.
The specialist AI agent effectively fills the gap in medical and psychological services during OOH for transplant recipients. Based on the “dual-source knowledge base + GraphRAG + multi-agent framework” architecture, our specialist AI agent offers safe, reliable post-transplant care.
To develop and internally validate an interpretable machine-learning model using routine precollection variables to predict mononuclear cell (MNC) collection efficiency (CE) during leukapheresis for CAR-T manufacturing.
This retrospective study included 206 consecutive patients who underwent leukapheresis between 2022 and 2025. Candidate variables were screened with Pearson correlation, Boruta, recursive feature elimination, and variance-threshold filters. Six supervised algorithms were trained with nested cross-validation, using an inner fivefold loop for tuning and an outer tenfold loop repeated three times for performance estimation. Bootstrap resampling (1000 iterations) generated confidence intervals, and SHAP analysis was used for interpretation.
Extreme gradient boosting (XGBoost) showed the best continuous prediction performance, with an R2 of 0.67 (95% CI: 0.64–0.70), Pearson r = 0.82, RMSE = 12.4%, and MAE = 9.8%. In the secondary triage analysis, observed high CE was defined as CE ≥ 60% (33/206, 16.0%). The predicted CE score discriminated high CE with an AUC of 0.84. A predicted-CE threshold of ≥ 50% yielded sensitivity of 84.8%, specificity of 97.1%, PPV of 84.8%, and NPV of 97.1%. The leading predictors were precollection lymphocyte count, lymphocyte/WBC ratio, age, body surface area, and monocyte count.
Routine precollection variables estimated MNC CE with good internal validity and may support individualized leukapheresis planning before CAR-T manufacturing.
Peptic ulcer disease (PUD) represents an ongoing global public health concern and is responsible for significant illness and mortality. Despite considerable advancements in medical therapy, the distribution and overall burden of PUD vary substantially across different regions and population segments worldwide. This research provides a comprehensive analysis of the global PUD burden, examining trends from 1990 to 2021 and forecasting patterns until 2050. The findings of this research, which use the most up-to-date epidemiological data available, are significant for epidemiology and disease management.
We leveraged data from the Global Burden of Disease (GBD) 2021 study, which covers 195 countries and territories. Our analysis assessed key metrics of disease impact, including disability-adjusted life years (DALYs), mortality rates, incidence and prevalence data, years lived with disability (YLDs), and years of life lost (YLLs). We calculated age-standardized rates (ASRs) to allow for consistent comparisons across populations. Temporal changes were quantified using estimated annual percentage changes (EAPCs) derived from linear regression. Furthermore, we applied hierarchical cluster analysis to investigate regional patterns in the PUD burden. These methods were chosen because of their robustness and ability to provide a comprehensive understanding of the global burden of PUD.
PUD was responsible for an estimated 6.06 million DALYs in 2021 (ASR: 71.56 per 100,000). This burden increased substantially with advancing age, peaking among individuals aged 80 and above. Compared with females, males had higher DALY rates (ASR: 87.02 vs 57.05 per 100,000) and considerably higher mortality rates. Regions with low and low-middle sociodemographic index (SDI) presented the highest ASRs (e.g., 178.38 per 100,000 in low-SDI areas). The highest DALY rates were observed in South Asia and parts of sub-Saharan Africa. Between 1990 and 2021, the global DALY ASR decreased markedly (EAPC: −2.96), though absolute DALY numbers remained elevated in populous, low- to middle-SDI regions. Model-based projections (exponential smoothing and ARIMA), assuming the continuation of recent trends, suggest that ASRs may continue to decline through 2050.
Over the past three decades, the global age-standardized burden of PUD has markedly decreased. However, significant challenges remain, particularly for older adults, males, and individuals in low-SDI areas, such as South Asia and sub-Saharan Africa. Although forecasts suggest further reductions in ASRs, the overall burden, influenced by population changes, underscores the crucial need for ongoing, targeted prevention and control efforts. This should prioritize Helicobacter pylori detection and eradication, safer NSAID use with gastroprotection in high-risk patients, and improved access to timely diagnosis and emergency care for ulcer complications in low-SDI regions. These efforts should focus on high-risk groups and regions to ensure equitable progress and should be a priority for all healthcare professionals, researchers, and public health policymakers.
Transpapillary therapy remains a critical treatment modality for main pancreatic duct (MPD) injury after acute necrotizing pancreatitis. This study aimed to verify the factors linked to the technical success of transpapillary drainage by endoscopic retrograde cholangiopancreatography (ERCP) in managing MPD injury, and the impact of technical success on tube duration and overall survival.
A retrospective analysis was conducted on patients who underwent ERCP for MPD injuries following acute pancreatitis from May 2019 to April 2021. Univariate and multivariate logistic regression analyses were employed to identify factors associated with successful treatment. Kaplan–Meier curves were used to analyze the impact of technical success on tube duration and overall survival.
We included 63 patients in whom MPD opacification was achieved (43 technical successes and 20 failures). The technical success group had a significantly higher proportion of patients whose interval from onset of acute pancreatitis to endoscopic transpapillary drainage (IOP) was less than 90 days (58.14%) than the failure group (20.00%, P = 0.005). Multivariate analysis revealed that an IOP < 90 days (OR = 0.24, 95% CI: 0.06–0.91, P = 0.036) and MPD injury located outside the head and neck of the pancreas (OR = 4.66, 95% CI: 1.10–19.77, P = 0.036) were independently associated with technical success. Technical success was associated with a shorter median tube indwelling time (10.3 months, 95% CI: 7.3–13.3) compared to technical failure (16.8 months, 95% CI: 12.3–21.3, P = 0.025).
ERCP should be performed within 90 days in patients with MPD injury, and the procedure has a higher success rate when the injury occurs outside the head and neck of the pancreas. This technical success significantly shortens drainage tube indwelling time and improves patients’ quality of life.
To evaluate the associations between transcription factor (TF)-defined molecular lineages and the clinical characteristics of pituitary neuroendocrine tumors (PitNETs).
A retrospective cohort analysis was performed in 274 patients who underwent extra-pseudocapsular transsphenoidal resection. Tumors were classified by TF-defined lineage and invasion grade (0–3) and Knosp score. Group differences were tested, and predictors of gross total resection (GTR) were examined using hierarchical multivariable logistic regression.
TF-defined lineage classification improved diagnostic precision. Among tumors with an immunonegative hormone profile, 74.7% received a definitive lineage assignment. The pituitary transcription factor 1–growth hormone/prolactin (PIT1–GH/PRL) subgroup had the highest incidence and grade of invasion; SRY-box transcription factor 2 (SOX2) positivity was most frequent in this subgroup (41.7%), which also exhibited the lowest GTR rate (58.3%). SOX2-positive tumors were associated with significantly higher preoperative adrenocorticotropic hormone (ACTH) (median: 38.80 vs. 31.60 pg/mL, P = 0.032) and GH (median: 1.12 vs. 0.43 ng/mL, P = 0.046) levels. SOX2 positivity was 20.5% in multilineage tumors and 20.0% in the recurrent cohort (n = 20). Compared with Trouillas grade alone, the combination of invasion grade and intraoperative features (capsule status and vascularity) significantly improved the ability to predict GTR (AUC, 0.866 vs. 0.795; ΔAUC = 0.071; DeLong 95% CI, 0.022–0.120; P = 0.005).
The 2022 WHO TF-defined lineage system improves diagnostic precision and facilitates the interpretation of PitNET differentiation and molecular pathology. Tumors in the PIT1–GH/PRL subgroup demonstrate more aggressive invasive features. SOX2 positivity was relatively frequent in multilineage tumors, whereas the observation in recurrent cases was limited by the small exploratory cohort and requires validation in larger longitudinal studies.
Previous studies have confirmed the opioid-sparing and analgesic properties of perioperative esmolol, yet relevant clinical evidence specifically focusing on patients with ischemic heart disease (IHD) remains scarce, and the spinal nociceptive mechanism underlying esmolol-induced pain relief has not been fully elucidated. This study aimed to investigate the association between perioperative esmolol administration and early postoperative opioid demand in IHD patients undergoing elective non-cardiac surgery, and further explore the role of spinal 5-hydroxytryptamine (5-HT)/5-HT2B signaling in incisional pain using a female rat plantar incision model.
For the clinical retrospective cohort, eligible IHD patients were divided into esmolol-exposed and non-exposed groups balanced via 1:1 propensity score matching. The primary outcome was cumulative 24-h postoperative opioid consumption converted to intravenous morphine equivalents (IME); secondary endpoints included early Numeric Rating Scale (NRS) pain scores, opioid-related adverse events and perioperative cardiovascular safety indicators. In animal experiments, intrathecal esmolol or selective 5-HT2B antagonist RS127445 was delivered to the female rats with plantar incision, followed by detection of mechanical withdrawal thresholds and spinal 5-HT/5-HT2B expression.
After matching, 52 patients were included in each group. Perioperative esmolol was associated with a 3.0 mg reduction in 24 h IME (mean difference [MD] = −3.0, 95% CI [−4.9, −1.1], P = 0.002), alongside lower post-anesthesia care unit (PACU) opioid consumption (MD = −2.3, 95% CI [−4.2, − 0.3], P = 0.022) and decreased resting NRS scores in PACU (MD = −0.8, 95% CI [−1.3, −0.2], P = 0.006) and at postoperative 6 h (MD = −0.6, 95% CI [−1.1, −0.02], P = 0.043); no intergroup difference in NRS was observed at 24 h (P = 0.379). All opioid-related adverse events showed comparable incidence between groups (all P > 0.05). Intraoperative heart rate was significantly lower in the esmolol group (MD = −4.4 beats/min, 95% CI [−7.8, −1.0], P = 0.012), while intraoperative mean arterial pressure (MAP) and major cardiovascular complications exhibited no between-group differences (all P > 0.05). In rats, the results revealed transiently elevated paw withdrawal mechanical thresholds after intrathecal esmolol (P < 0.05 at 5 and 10 min), accompanied by suppressed surgery-induced upregulation of spinal 5-HT and 5-HT2B protein (P < 0.05). Intrathecal RS127445 also significantly alleviated mechanical hypersensitivity at 1 h post-administration (P < 0.01), with loss of efficacy at 2 h (P > 0.05).
Perioperative esmolol is associated with early opioid-sparing and mild relief of acute postoperative pain in IHD patients receiving elective non-cardiac surgery, without increasing cardiovascular risks, whereas this regimen fails to reduce opioid-associated side effects. Preclinical data suggest that spinal 5-HT/5-HT2B signaling contributes to incision-induced mechanical hyperalgesia and may mediate the transient analgesic effect of esmolol.
To overcome the trade-off between the low viscosity required for printability and the high mechanical strength required for functionality in dental resins for vat photopolymerization 3D printing by developing a hydrogen-bond engineering strategy.
Three dental oligomers (Bis-GMA, UDMA, and Bis-EMA) were blended with four diluents differing in hydrogen-bonding ability. Fourier transform infrared (FTIR) spectroscopy, rheometry, three-point bending tests and 3D printing performance tests were carried out to evaluate hydrogen bond formation, viscosity, mechanical properties, printability and accuracy.
FTIR and rheological tests confirmed strong hydrogen bonding between MAA and matrix oligomers. The optimized formulation, n(MAA): n(UDMA) = 2:1, achieved flexural strengths of 228 MPa (mold-filled) and 178 MPa (3D-printed) and elastic modulus of 5.3 GPa and 4.0 GPa, respectively, whereas the viscosity was only 307 mPa·s—a dramatic improvement over that of neat UDMA (viscosity 9689 mPa·s, mold-filled mechanical strength 174 MPa and 3.8 GPa). The hydrogen-bonding diluents also demonstrated significant advantages in composite resin formulations.
Hydrogen bond engineering decouples viscosity from mechanical strength, enabling the fabrication of low-viscosity, high-strength dental resins for 3D printing. This scalable platform overcomes the longstanding viscosity–strength trade-off, offering promising potential for dentistry and other fields of photocurable additive manufacturing.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality rates. While previous studies have focused primarily on the epidemiological and clinical aspects of SFTS, indicators of renal injury at admission have received limited attention.
We retrospectively analyzed 260 patients with SFTS admitted to the study hospital between April 1, 2023, and July 18, 2024, who were classified into the survival group (n = 163) and death group (n = 97) on the basis of 28-day prognosis. Renal-related data were collected upon admission. Univariate and multivariate Cox regression analyses were used to identify independent predictors, and a nomogram was constructed. Receiver operating characteristic (ROC) curves and calibration curves were used to assess the discrimination and calibration of the model. Kaplan–Meier curves were used to assess the cumulative survival rate of patients with these risk factors. External validation was conducted in 40 patients with SFTS who were admitted to an affiliated branch hospital during the same period.
The 28-day mortality rate was 37.3% (97/260). Multivariate analysis revealed age (HR = 1.053; 95% CI 1.027–1.079; P < 0.001), viral load (HR = 2.006; 95% CI 1.684–2.390; P < 0.001), and UREA (HR = 1.059; 95% CI 1.027–1.093; P < 0.001) as independent risk factors. The area under the curve (AUC) of the nomogram was 0.900 (95% CI 0.861–0.937), with 82.5% sensitivity and 84.0% specificity at the optimal cutoff (0.292). The calibration curve showed close agreement between the predicted and observed probability lines, indicating good model calibration. External validation yielded an AUC of 0.863 (95% CI 0.723–0.954), confirming favorable performance.
Renal injury-related indicators at admission were strongly associated with fatal outcomes in patients with SFTS. Nomograms based on age, viral load, and UREA provide accurate and easily applicable tools for early risk stratification and may support individualized clinical management.
To investigate the contribution of endoplasmic reticulum (ER) stress to the progression of thyroid cancer (TC) and to construct a prognostic gene signature.
Differential expression analysis was performed on 572 samples from The Cancer Genome Atlas (TCGA). ER stress-related genes (ERSGs) were obtained from the GeneCards database. Overlap analysis revealed 178 differentially expressed ERSGs. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were used to construct a prognostic risk model. The model was validated in a test set (n = 172) and an independent clinical cohort (n = 90) by RT-qPCR. Immune infiltration, immune checkpoint expression, and drug sensitivity were compared between the high- and low-risk groups using the CIBERSORT algorithm and the Genomics of Drug Sensitivity in Cancer (GDSC) database.
A total of 5,253 differentially expressed genes and 518 ERSGs were identified, yielding 178 overlapping genes. An 11-gene prognostic model (CDKN1A, HTR2A, ATF3, MTTP, BRSK2, EGF, CASP12, HSPA5, IL1A, FOXRED2, CASQ2) was constructed. Patients in the high-risk group had significantly worse overall survival than those in the low-risk group did (log-rank P < 0.001; hazard ratio [HR] = 2.34; 95% CI: 1.58–3.47). The model showed good predictive performance, with AUC values of 0.74, 0.72, and 0.71 for 1-, 3-, and 5-year overall survival, respectively. Significant differences in tumor immune cell infiltration (e.g., Tregs, P < 0.01; M2 macrophages, P < 0.05) and drug sensitivity (e.g., gefitinib, P < 0.05) were detected between the two groups. In 90 clinical samples, the expression patterns of the 11 genes were validated by RT-qPCR (all P < 0.05), which was consistent with the bioinformatics findings.
The 11-gene ER stress-related signature independently predicted prognosis in patients with TC across both the TCGA cohort and an independent cohort. This study provides new insight into the role of ER stress in TC and may facilitate the identification of prognostic biomarkers and support clinical decision-making.
Emerging evidence suggests the involvement of the renin-angiotensin system (RAS) in the pathogenesis and progression of autoimmune dermatological diseases. In a small exploratory study, we investigated angiotensin-converting enzyme (ACE) activity in blood obtained from male probands with psoriasis vulgaris (n = 4) and atopic dermatitis (AD, n = 5).
The degradation capacity of dabsylated synthetic bradykinin (DBK) with and without inhibition was determined using a thin-layer chromatography (TLC)-based neuropeptide reporter assay.
We observed a significantly reduced capacity for cleavage of DBK in psoriasis patients compared with that in AD patients and controls. In patient samples, the variation in the measured values was generally greater than that in healthy controls. We could not confirm the increased ACE activity in the circulation in psoriasis patients reported by others, likely because of different study designs and detection methods. We did not include samples of female patients and focused on younger men to avoid hormonal effects and minimize age-related factors.
This preliminary study of the hypothesis-generating nature lacks power, but it certainly adds a question to the current view of the role of ACE in psoriasis. Treatments targeting specific components of the RAS could ameliorate inflammatory responses; thus, research in this area is becoming increasingly important.
To investigate the feasibility of 2D convolutional neural networks (CNNs) in the automatic classification of anterior talofibular ligaments (ATFLs) on MR images.
A total of 560 transverse T2-weighted MR images of the ATFL were collected from Center A, and 96 from Center B; manual segmentation of the ATFL was performed. The ATFL segmentation model was trained on YOLO11 and was validated on images from Center B. The dice similarity coefficient (DSC) between manual and automatic segmentation was calculated. A total of 1,103 T2-weighted MR images of the ATFL were further collected from Center C and divided into three groups: normal, partial, and total tear, and ATFL was automatically segmented for all the images. The 2D ResNet model was then trained for ATFL classification. Finally, the segmentation model and classification model were applied to 420 images from Center D.
The median DSC for the YOLO11 segmentation model was 0.95. For Center D data, the automatic workflow achieved an accuracy of 92.6% (389/420). It showed 95.0% (190/200) sensitivity and 93.6% (206/220) specificity for abnormal ATFL detection, slightly below the junior radiologist’s 97.0% (194/200) sensitivity and 95.5% (210/220) specificity, but the difference did not reach statistical significance (P = 0.22). Automatic classification of the Center D dataset took 3 minutes, compared with manual 14 minutes for the junior radiologist.
Automatic segmentation and classification of ATFL on MR images based on CNNs are feasible for evaluating ATFL.
Sepsis is a dysregulated response of the host to infection that can lead to life-threatening organ dysfunction and remains a leading cause of mortality. Early recovery of impaired organ function is crucial for the outcomes of sepsis. Electroacupuncture (EA) is a promising adjunctive therapy for sepsis, but no study has focused on the efficacy of EA for organ dysfunction. This study aimed to investigate the efficacy and safety of EA in improving organ dysfunction among intensive care unit (ICU) patients with sepsis.
In this single-center, randomized, sham-controlled clinical trial, an adaptive sample size of 154–500 patients diagnosed with sepsis will be included. Eligible patients will be randomly assigned to receive EA or sham EA treatment at a 1:1 ratio using block randomization. Patients in the two groups will receive 6 consecutive sessions of 30-min EA or sham EA treatment, with the initial acupuncture treatment being completed within 24 h after randomization. The primary outcome is the change in the total score of the Sepsis-Related Sequential Organ Failure Assessment (SOFA) on day 7 after randomization compared with baseline. Secondary outcomes include changes in the SOFA score and related serological outcomes, mortality, ICU-free days, hospital-free days and organ support-free days from baseline to day 28. Statistical analyses will be performed on a full analysis set (FAS) and a per-protocol set (PPS).
We expect the findings of this trial to provide evidence that the use of EA as an adjunctive therapy to ICU treatment can promote the recovery of organ function and other outcomes in sepsis patients.
ClinicalTrials.gov identifier: NCT06666946. Registered on 28 October 2024.