BACKGROUND:Hematopoietic stem cell transplantation (HSCT) cures many hematologic malignancies, but peri‑engraftment complications like delayed engraftment and high transfusion requirements remain challenging. Prior studies examined the independent effects of transplant type, hemoglobin, and platelets on post‑transplant outcomes, but whether their associations with these outcomes vary by transplant type is unknown. METHODS:In this retrospective cohort of 341 HSCT patients, we examined whether the associations between pre-transplant hemoglobin and platelet levels and four key peri-engraftment outcomes (RBC transfusion volume, granulocyte engraftment time, megakaryocyte engraftment time, and platelet transfusion requirements) varied by transplant type (allogeneic vs. autologous). Multiple linear regression models for each outcome included diagnosis, transplant type,centered CD34+(C_CD34+),centered prothrombin time (C_PT), centered hemoglobin (C_Hb),and centered platelet (C_PLT) as main effects, with interaction terms: transplant type × C_Hb and transplant type × C_PLT. Bootstrap with 1000 resamples was used to estimate 95% CIs. RESULTS:The transplant type × hemoglobin interaction was significant for granulocyte engraftment time (p = 0.014) and RBC transfusion volume (p = 0.029). Simple slope analyses showed that the adverse effect of allogeneic transplantation was largest at low hemoglobin (-1 SD: +2.67 days , +2.93 units) and smallest at high hemoglobin (+1 SD: +1.48 days , +1.43 units). No significant interactions were observed for platelet‑related outcomes (all p > 0.05). CONCLUSIONS:Higher pre‑transplant hemoglobin attenuated the adverse effects of allogeneic HSCT on granulocyte recovery and RBC transfusion requirements, suggesting baseline hemoglobin may serve as a useful risk indicator for peri‑engraftment management in allogeneic recipients, warranting prospective validation.
Introduction The curriculum of the Doctor of Medicine program at The University of Kansas School of Medicine includes a substantial portion of content delivered via small-group, case-based collaborative learning (CBCL) activities. As critical stakeholders in continuous quality improvement in their education, medical students are poised to make contributions to curriculum enhancement, though they are often underutilized resources.Methods Without a faculty-led curriculum revision committee, we piloted a student-led Case-Based Collaborative Learning Review Committee (SCRC) to systematically incorporate student feedback into curriculum revision efforts by reviewing three CBCL activities. The SCRC provided structured anonymous edits and feedback to faculty authors. Qualitative (thematic) data analysis used mixed methods to assess the intervention’s impact and develop guidance for future iterations.Results Sessions were well-received by participating students and receiving faculty based on satisfaction surveys. Thematic analysis of student-generated suggested edits revealed five primary categories of revisions: simple edits, pre-work recommendations, relevancy of social constructs, clarification, and ‘need more’.Conclusion Overall, the intervention demonstrated that student-led review was feasible and yielded valuable multi-level feedback on small-group learning activities, such as CBCL. Further research could help determine if similar work could be feasible and effective for lectures and flipped classroom material and whether such continuous quality improvement should be required in our medical education curriculum processes.
BACKGROUND:Spinal muscular atrophy (SMA) is a recessively inherited autosomal neuromuscular disorder that is associated with deletions or disease-causing variants in the survival motor neuron 1 (SMN1) gene. Delayed diagnosis of SMA remains a common issue worldwide, particularly in regions with unequal medical resources. CASE PRESENTATION:Patient 1 was a 21-year-old man who had experienced limb weakness and muscle atrophy for 20 years. At the age of 6, he underwent genetic testing and was diagnosed with SMA type II. Patient 2 was a 26-year-old man who had been complaining of progressive limb weakness for 11 years and muscle atrophy for 5 years. When he was 20 years old, he experienced muscle atrophy of both legs and was diagnosed with SMA type III after genetic testing. Patient 3 was a 40-year-old man who presented with slowly progressive lower limb weakness since the age of 15. He was misdiagnosed with Duchenne muscular dystrophy in age 20. He was referred to our clinic at the age 40 and was ultimately confirmed to have SMA after genetic testing. Patients 4 and 5 were sisters, who complained of lower limb weakness and were recently diagnosed with SMA. CONCLUSIONS:This case series highlights the current status and possible reasons for delayed diagnosis and delayed initiation of treatment for SMA, including limited awareness of SMA, low accessibility of genetic testing, and uneven distribution of medical resources.
Background Pulmonary arterial hypertension (PAH) causes substantial premature mortality and disability. Updated evidence comparing long-term PAH burden in China with the Group of Twenty (G20) aggregate remains limited. We assessed changes from 1990 to 2023 and projected future trends.Methods PAH estimates for China and the G20 aggregate were extracted from the Global Burden of Disease Study 2023. Outcomes included incidence, prevalence, deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs), expressed as absolute counts and age-standardized rates. Temporal trends were assessed using Joinpoint regression. Sex-specific and age-specific patterns and demographic decomposition were examined. Autoregressive integrated moving average (ARIMA) models projected overall burden through 2050. Bayesian age-period-cohort (BAPC) models projected sex-specific patterns through 2038.Results From 1990 to 2023, incident and prevalent cases and YLDs increased in both settings, whereas deaths, DALYs, and YLLs declined. In China, prevalent cases increased by 63.5%, from 17,020.87 to 27,834.41, while the age-standardized death rate decreased by 74.3%, from 0.29 to 0.08 per 100,000 population. Similar declines in mortality-related age-standardized indicators occurred in the G20 aggregate. Females generally had higher age-standardized prevalence and YLD rates than males, although sex differences in mortality-related outcomes varied by setting. Absolute burden shifted toward older age groups. Population growth and aging contributed to increases in absolute burden, whereas epidemiological change generally acted in the opposite direction. Projections suggested continued declines in age-standardized mortality-related burden through 2050, alongside increases in incident and prevalent case numbers.Conclusion Mortality-related PAH burden declined in China and the G20 aggregate, while absolute case numbers increased. Population growth and aging contributed to this divergence, underscoring the need for continued surveillance and long-term health-service planning.
BACKGROUND:Conventional age <50 versus ≥50 years grouping may obscure colorectal cancer (CRC) burden patterns around the contemporary screening boundary. We examined whether adults aged 45-49 years occupy a threshold-adjacent position not captured by conventional grouping. METHODS:Using GBD 2023 data, we analyzed CRC incidence, deaths, and DALYs from 1990 to 2023 across four age groups (15-44, 45-49, 50-74, 75+ years). We assessed global and SDI-stratified trends, inequality, empirical lower-bound burden frontiers, and decomposition of burden change. Sensitivity analyses included conventional age regrouping, High versus Non-High SDI decomposition, split-period analyses, and adjacent 5-year age-group comparisons. RESULTS:Incidence rose most in adults aged 15-44 (+16.8%) and 45-49 years (+11.0%), with smaller increases in those aged 50-74 (+7.5%) and 75+ (+3.6%). Deaths and DALYs declined more clearly above age 50. In adults aged 45-49, incidence inequality remained positive but narrowed (CI: 0.304 to 0.253; relative SII: 1.693 to 1.412), while DALY inequality weakened (CI: 0.159 to 0.068). During 2010-2023, the residual rate-change component contributed positively to incidence in adults aged 45-49 globally (31.5%) but was slightly negative in those aged 50-74 (-2.6%). Post-2018 amplification in High-SDI populations was consistent with screening-related detection effects. CONCLUSIONS:Adults aged 45-49 occupy a context-dependent threshold-adjacent position in global CRC burden redistribution. These findings inform population-level surveillance and policy evaluation rather than individual-level clinical decision-making.
BACKGROUND:The role of preoperative β-blocker therapy in patients with ventricular dysfunction undergoing coronary artery bypass grafting (CABG) remains unclear. OBJECTIVE:We aim to evaluate heterogeneous treatment effects of preoperative β-blocker therapy in patients with ventricular dysfunction undergoing CABG and to identify subgroups that may derive greater benefit from preoperative β-blocker therapy than untreated controls. METHODS:To investigate the heterogeneous treatment effects of preoperative β-blocker therapy on 30-day mortality in patients with ventricular dysfunction undergoing CABG, we analyzed data on 6,492 patients in the Chinese Cardiac Surgery Registry database between 2017 and 2020. After propensity score matching, we applied a machine-learning iterative causal forest (iCF) algorithm to estimate individualized treatment effects (ITEs) of β-blockers on 30-day all-cause mortality after CABG. RESULTS:The iCF models showed heterogeneity in the effects of preoperative β-blockers on 30-day mortality. Estimated glomerular filtration rate (eGFR), left ventricular end-diastolic diameter (LVEDD) and body mass index (BMI) were identified by the algorithm to distinguish patients with heterogeneous treatment effects. Among patients with eGFR 66 mL/min/1.73 m2 or less, preoperative β-blocker therapy was associated with a significantly lower risk of death from any cause (adjusted odds ratio [aOR], 0.39; 95% CI, 0.22 to 0.67; p = 0.001). No significant benefits were found for other subgroups. CONCLUSION:Machine learning analysis revealed treatment effect heterogeneity, with preoperative β-blockers demonstrating superior outcomes specifically in CABG patients with ventricular dysfunction and concomitant renal dysfunction (eGFR ≤ 66 mL/min/1.73 m2).
BACKGROUND:Perioperative administration of esketamine has been reported to improve early quality of recovery (QoR). However, data on its effects in outpatient surgery are limited. This study aimed to assess the impact of esketamine on QoR in patients undergoing outpatient gynecological procedures. METHODS:In this investigator-initiated, double-blind, randomized clinical trial, patients aged 18-65 years scheduled for outpatient gynecological surgery under sedation were allocated to receive esketamine (0.2 mg/kg) or sufentanil (0.1 μg/kg) combined with propofol (1.5-3 mg/kg). The primary outcome was quality of recovery on postoperative day (POD) 1. Secondary outcomes included quality of recovery on POD2, sedation success rate, length of post-anesthesia care unit (PACU) stay, injection pain, postoperative pain, nausea and vomiting, fatigue, patient and clinician satisfaction, sleep quality, and anxiety and depression. RESULTS:A total of 126 patients were randomized, with 63 assigned to the esketamine group and 63 to the sufentanil group. Of these, 125 patients were included in the final analysis (62 in the esketamine group and 63 in the sufentanil group), as one patient lacked follow-up data. The mean (SD) QoR-15 score on POD1 was 137.9 (14.5) in the esketamine group and 137.8 (10.7) in the sufentanil group, with no significant difference between groups (absolute difference, 0.2; 95% CI, -4.2 to 4.6; p = 0.93). For secondary outcomes, the esketamine group had a longer PACU stay (median, 28.0 vs. 23.0 min; p < 0.001), a lower incidence of severe injection pain (22.6% vs. 50.8%; p = 0.002), a higher proportion of patients with pain scores ≥ 4 at 30 min postoperatively (30.6% vs. 6.3%; p = 0.001), and higher fatigue scores (median, 3.0 vs. 2.0; p = 0.01). Other secondary outcomes did not differ significantly between groups. CONCLUSION:Among patients undergoing sedation for outpatient gynecological procedures, esketamine did not significantly improve quality of recovery on POD1 compared to sufentanil. TRIAL REGISTRATION:Chinese Clinical Trial Registry, ChiCTR2500098466.
BACKGROUND:The country-level co-burden of esophageal cancer and lip and oral cavity cancer (LOC) among older adults remains poorly characterised. We examined global spatiotemporal patterns and associated population-level exposures. MATERIALS AND METHODS:We analyzed Global Burden of Disease 2021 data for adults ≥ 55 years across 203 countries and territories. Incidence rates were classified into quartile-based co-burden categories, comparing 1990-2021 trends with Socio-demographic Index (SDI) trajectories. After screening 58 candidate exposures, random forests and SHapley Additive exPlanations ranked 36. Following variance inflation factor screening, the top 25 entered multivariable negative binomial models with population offsets. RESULTS:Countries and territories were classified as consistent (n=73), esophageal cancer-dominant (n=61), or LOC-dominant (n=69). Increasing SDI generally coincided with declining esophageal cancer incidence, whereas LOC incidence increased in several high-SDI settings. Both cancers were associated with high alcohol use (esophageal RR=1.32, 95% CI: 1.13-1.53; LOC RR=1.27, 95% CI: 1.13-1.43) and diets low in nuts and seeds (esophageal RR=1.16, 95% CI: 1.05-1.27; LOC RR=1.08, 95% CI: 1.01-1.16). Esophageal cancer was additionally associated with iron deficiency (RR=1.31, 95% CI: 1.14-1.52), occupational exposure to particulate matter, gases, and fumes(RR=1.29, 95% CI: 1.13-1.49), and high red meat diets (RR=1.16, 95% CI: 1.02-1.33). LOC was associated with chewing tobacco (RR=1.32, 95% CI: 1.22-1.44) and high-sodium diets (RR=1.10, 95% CI: 1.01-1.20). CONCLUSIONS:These ecological associations indicate geographic heterogeneity in cancer co-burden and exposure profiles, informing regionally tailored prevention priorities without establishing individual-level causality.
BACKGROUND:Acute type A aortic dissection (ATAAD) is associated with a high risk of postoperative severe organ dysfunction. Preoperative risk scores alone may not capture early postoperative pathophysiological recovery. This study aimed to develop and temporally validate a dynamic inflammation-perfusion-coagulation recovery failure index (dIPC-RFI), based on routinely available preoperative, immediate postoperative, and 24-hour postoperative laboratory and blood gas variables, for risk restratification of severe organ dysfunction beyond 24 h after ATAAD surgery. METHODS:Patients with ATAAD who underwent emergency surgical repair at The University of Hong Kong-Shenzhen Hospital between August 2021 and December 2025 were retrospectively included. Postoperative 24 h was used as the fixed risk-assessment starting point; only patients who were alive, free from the primary outcome, and had complete variables required for dIPC-RFI assessment at 24 h were included. Patients were split chronologically into a derivation cohort (first 70%) and a temporal validation cohort (last 30%). The primary outcome was severe organ dysfunction occurring after 24 h until discharge or within 30 days, defined as any of the following: continuous renal replacement therapy, mechanical ventilation for ≥72 h, neurological complications, multiple organ dysfunction syndrome, in-hospital death after 24 h or 30-day death, intra-aortic balloon pump support, extracorporeal membrane oxygenation, or tracheostomy. dIPC-RFI consisted of three domains-inflammation, perfusion, and coagulation-each including one static 24-hour variable and one dynamic change variable. Cutoffs were derived using receiver operating characteristic curves and the Youden index in the derivation cohort and then fixed for the validation cohort. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), Brier score, calibration curve, calibration intercept and slope, and decision curve analysis. RESULTS:A total of 330 patients were included, of whom 134 (40.6%) developed severe organ dysfunction after 24 h. Event rates were 39.0% in the derivation cohort and 44.4% in the temporal validation cohort (p = 0.392). In the validation cohort, dIPC-RFI achieved an AUC of 0.873 (95% CI, 0.794-0.935) and a Brier score of 0.1387, outperforming the simplified clinical model (AUC = 0.762) and the extended clinical model (AUC = 0.735). The combined model integrating the simplified clinical model and dIPC-RFI further improved discrimination (AUC = 0.908) and reduced the Brier score to 0.1243. Component-specific analyses showed acceptable discrimination for major components with sufficient validation events, including CRRT, prolonged mechanical ventilation, neurological complications, and MODS component. The no-CRRT sensitivity analysis and the death-or-MODS sensitivity analysis supported the robustness of the main findings. CONCLUSIONS:dIPC-RFI provides a simple 24-hour postoperative framework for identifying incomplete recovery across inflammation, perfusion, and coagulation after ATAAD surgery. It may help ICU teams identify patients who require intensified monitoring, repeated lactate and coagulation assessment, early multidisciplinary review, and preparation for organ support. dIPC-RFI should be used as a risk-restratification aid rather than a stand-alone treatment trigger, and prospective multicenter validation is required before routine implementation.
OBJECTIVE:To evaluate the predictive value of the preoperative haemoglobin-albumin-lymphocyte-platelet (HALP) index for in-hospital mortality in patients undergoing cardiopulmonary bypass (CPB)-assisted type A aortic dissection surgery. METHODS:This single-centre retrospective cohort study enrolled 750 adult patients who underwent type A aortic dissection surgery with CPB at a tertiary hospital from January 2021 to December 2025. The HALP index was calculated using preoperative laboratory data, with in-hospital mortality as the primary endpoint. Variables with p < 0.1 in univariate analysis were included in multivariate logistic regression to identify independent risk factors, and receiver operating characteristic (ROC) curves were used to assess the predictive performance of HALP and the combined model. RESULTS:The in-hospital mortality rate was 12.8%. Patients in the mortality group had significantly lower HALP scores than survivors (49.27 ± 15.06 vs. 71.53 ± 25.98). Multivariate analysis identified age (OR = 1.06), chronic kidney disease (CKD) (OR = 2.71), reduced left ventricular ejection fraction (LVEF) (OR = 0.92) and low HALP (OR = 2.87) as independent predictors. ROC analysis showed that HALP (area under the curve (AUC) = 0.74) outperformed individual indicators (age, CKD, LVEF: AUC 0.60-0.65), and the combined model achieved the best predictive performance (AUC = 0.79). CONCLUSIONS:The preoperative HALP index is an independent predictor of in-hospital mortality after type A aortic dissection surgery with CPB, with good discriminatory performance. As a simple and low-cost biomarker, it effectively supplements traditional risk scoring systems and supports preoperative risk stratification and clinical decision-making. Specifically, patients with low HALP values at admission may benefit from proactive blood product preparation, early nutritional support and intensified postoperative monitoring, thereby optimizing perioperative management and improving outcomes.
BACKGROUND:Alpha-Gal syndrome (AGS) is a growing burden worldwide associated with arthropods and allergies with pathologies such as urticaria, digestive and anaphylactic reactions. These reactions commonly appear 2-6 h after consumption of mammalian meat and derived pharmaceuticals mediated by immunoglobulin E against the oligosaccharide alpha-Gal epitope. OBJECTIVE:Despite the increasing incidence of AGS, it is underdiagnosed and requires information and initiatives to reduce disease risks and incidence while improving prevention and treatment. CONTENT:Our hypothesis is that Galactosyltransferase associated with alpha-Gal synthesis appeared and evolved in bacteria during the Mesoproterozoic Era ca. 1000 million years ago (Mya). Then, in Mollusca during the Cambrian and in Arthropoda and Mammalia during the Triassic period associated with improved fitness in organisms repopulating the Earth after Permian-Triassic Great Dying extinction event but affected Hominidae leading to catastrophic selection in the Oligocene. CONCLUSIONS:With global rapidly changing climate and population dynamics, it should be considered that multiple arthropod species evolved to synthesize alpha-Gal as a guidance to develop preventive and control measures to reduce the risks of exposure to AGS. Accordingly, research should focus on the role of other organisms in addition to ticks in the evaluation and prevention of risks associated with the AGS with education for patients and medical staff to improve prevention and management of patients with AGS.Key messagesThe alpha-Gal synthesis evolved across multiple Arthropoda, Mollusca and MammaliaHominids developed to produce anti-alpha-Gal antibodies with protective capacityAlpha-Gal syndrome (AGS) in humans is associated with arthropods and allergic reactionsOther organisms are potential overlooked sources of alpha-gal.
BACKGROUND:The Kessler Psychological Distress Scale (K6) is in widespread use to screen for psychological distress, but evidence to support the quality of the Japanese version (JK6) remains limited, in particular with respect to item response theory (IRT)-based item parameters and the test information function (TIF). Evidence concerning measurement invariance across gender and age groups likewise remains limited. Therefore, this study examined the structural validity and measurement invariance of the JK6 in an online community sample of 6632 Japanese-speaking adults aged 20-59 years. MATERIALS AND METHODS:Confirmatory factor analysis (CFA) was used to compare one- and two-factor models. Using IRT with a graded response model, item discrimination and threshold parameters were estimated and item information functions and the TIF were derived. Measurement invariance across gender and age groups was tested using multi-group CFA (MCFA), and differential item functioning (DIF) was examined via ordinal logistic regression. RESULTS:The CFA results supported a primarily unidimensional interpretation of the JK6. IRT analyses showed very high item discrimination, and the TIF indicated high measurement precision for mild-to-moderate levels of psychological distress. MCFA supported scalar invariance across gender and age groups, and the DIF effect sizes were negligible. CONCLUSIONS:These findings indicate that the JK6 is a primarily unidimensional measure of psychological distress that provided precise and comparable assessment across gender and age groups in an online community sample of Japanese-speaking adults aged 20-59 years. Further studies should be undertaken to examine the generalizability of these findings across the broader Japanese adult population, including older adults and clinical populations.
BACKGROUND:Implant-based breast reconstruction after mastectomy causes acute pain. OBJECTIVE:To determine whether a single-shot T5 erector spinae plane block (ESPB) reduces postoperative pain. DESIGN:Single-center, RCT with allocation concealment; blinded assessors and statisticians. SETTING:Tertiary cancer center in China. PATIENTS:100 adults scheduled for radical mastectomy with implant reconstruction were randomized (1:1); follow-up complete. INTERVENTION:Before induction, ESPB was given under ultrasound guidance at T5 with 30 mL of 0.375% ropivacaine plus dexmedetomidine 1 μg/kg; controls received no block. Standardized general anesthesia and postoperative PCA for both groups. MAIN OUTCOME MEASURES:Resting NRS at 6 h (MCID=1). Secondary outcomes were opioid consumption, quality of recovery, and PONV. RESULTS:ESPB did not significantly reduce resting pain at 6 h at the median (τ =0.50; adjusted difference -0.9; p = 0.08). At the upper tail, pain intensity was lower (τ = 0.75; -1.8; p <0.01). Repeated measures provided additional time-point information, improving estimation precision and test sensitivity. ESPB get lower pain scores at 6, 12, and 24 hours (all p <0.01). But, the 95% CI includes the MCID, the clinical benefit remains uncertain. Opioid use decreased at 24 h (-13.5 mg; p <0.01) and 48 h (-6.6 mg; p <0.01). Quality of recovery improved at 24 h (difference 5 points; p <0.01), but not later. No differences were observed in intraoperative hemodynamics or PONV. CONCLUSIONS:Single-shot T5 ESPB with perineural dexmedetomidine may reduce postoperative pain and opioid requirements and improve early recovery. Further large trials are warranted. Clinical relevance remains to be confirmed. TRIAL REGISTRATION:ClinicalTrials.gov NCT06143020.
BACKGROUND:Obesity, purine metabolism disorders, and dyslipidemia are recognized risk factors for sarcopenia, yet reliable biomarkers for risk stratification in this population are lacking. We integrated the uric acid to high-density lipoprotein cholesterol ratio (UHR) with the body roundness index (BRI) to construct a multiple composite risk index, UHR-BRI, and evaluated its associations with sarcopenia and its comorbidities. METHODS:We analyzed two nationally representative cohorts: the China Health and Retirement Longitudinal Study (CHARLS) and the National Health and Nutrition Examination Survey (NHANES). The association between UHR-BRI and sarcopenia was evaluated using weighted logistic regression. Subgroup and mediation analyses were performed to investigate the interactions across subgroups, and the mediating role of oxidative balance score (OBS). RESULTS:A total of 8,537 participants from CHARLS and 8,510 from NHANES were included, among whom 1,082 and 716 were diagnosed with sarcopenia. The area under the curve (AUC) value of the UHR-BRI index was higher than that of the other indices in both cohorts. In fully adjusted models, participants in the highest UHR-BRI quartile exhibited a significantly increased risk of sarcopenia (OR:3.01, 95% CI:2.45-3.72) compared to those in the lowest quartile in CHARLS. This finding was validated in NHANES (OR:17.14, 95% CI:11.55-26.60). Subgroup analyses further demonstrated robustness across different subgroups. Furthermore, UHR-BRI was also significantly associated with sarcopenia comorbidities. Mediation analyses confirmed that OBS mediated the associations between UHR-BRI and sarcopenia and its comorbidities. CONCLUSION:UHR-BRI is significantly associated with sarcopenia and its common comorbidities, and OBS was identified as a potential mediator.
BACKGROUND:Olfactory dysfunction is associated with adverse health outcomes such as neurodegenerative diseases. However, few large-scale epidemiological studies in China have focused on olfactory function using psychophysical testing. This study seeks to investigate the prevalence of olfactory dysfunction among healthy adults through a large-scale, nationwide survey and to examine its associations with demographic and other factors. METHODS:The study was conducted across multiple locations in China between 2023 and 2024, involving local residents aged 20 and above. A total of 12,153 participants underwent the T&T olfactometer test and completed a questionnaire survey. We reported the epidemiological burden of olfactory dysfunction and identify its demographic, behavioural and clinical correlates. RESULTS:The overall prevalence of olfactory dysfunction in the participants was 15.3%. Age (PR increased with age, ≥70 years PR = 54.70; 95% CI, 17.60-170.08; p < 0.01), rural residence (PR = 1.93; 95% CI, 1.76-2.12; p < 0.01), current smoking (PR = 1.20; 95% CI, 1.04-1.39; p < 0.01) and self-reported olfactory dysfunction (PR = 3.97; 95% CI, 3.61-4.37; p < 0.01) were independently associated with a higher prevalence of olfactory dysfunction, while being female (PR = 0.78; 95% CI, 0.71-0.85; p < 0.01), having more years of education (High school PR = 0.60; 95% CI, 0.54-0.66; College and above PR = 0.45; 95% CI, 0.38-0.52; p < 0.01), and higher income level (p < 0.01) were independently associated with lower prevalence. CONCLUSION:Large-scale olfactory screening with the T&T olfactometer is viable. The prevalence of olfactory dysfunction demonstrates a progressive increase with advancing age. Independent factors associated with olfactory dysfunction include male gender, residing in rural areas, having lower educational levels, low income, current smoking and self-reported olfactory dysfunction.
BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumour microenvironment (TME), which contributes to its resistance to immunotherapy. Although mast cells (MCs) have been implicated in PDAC progression, their functional heterogeneity and candidate signaling models of immune modulation remain poorly understood. METHODS:Through an integrated analysis of multiple single-cell RNA sequencing (scRNA-seq) datasets, we identified a significant enrichment of MCs in PDAC tissues and established a characteristic gene signature (TPSAB1, TPSB2, CPA3, HPGDS, KIT, LTC4S) for their precise identification. RESULTS:Single-cell RNA-seq analysis categorized MCs in PDAC into resting, activated, and proliferating subpopulations. To functionally validate these transcriptomic predictions, in vitro co-culture experiments showed that pancreatic cancer cells promote the activation and proliferation of MCs. Cell-cell communication analysis suggested that activated MCs preferentially interact with regulatory T cells (Tregs) via the MIF-(CD74/CXCR4) signaling axis. This interaction was associated with an immunosuppressive T-cell landscape, characterized by an expanded population of Tregs exhibiting a highly activated immunosuppressive phenotype. Spatial transcriptomics and immunofluorescence validated the confirmed the spatial proximity of MCs and Tregs in PDAC tissues. Clinically, high expression of MC-Treg signature genes correlated with poor patient survival. CONCLUSIONS:Our study suggests that MCs are key orchestrators of immunosuppression in PDAC, predicted to interact with Tregs through the MIF-CD74/CXCR4 axis, offering a novel rationale for targeting the MC-Treg axis in future immunotherapeutic strategies.
BACKGROUND/OBJECTIVE:Virtual reality (VR) exergaming enhances several cognitive domains through multisensory engagement. Acute cognitive benefits of VR are established, but evidence for direct comparisons with non-immersive controls is limited. This study aimed to determine whether VR exercise provides additional cognitive and cognitive-motor benefits beyond a matched non-immersive active stick-fight video (SFV) intervention, and whether effects persist after training. METHODS:In this randomized quasi-experimental study, N = 55 healthy adults (VR: n = 30; SFV: n = 25; 25.5 ± 7.1 years; 41.8% female) completed an 8-week program (2 × 30 min/week), of VR or SFV matched in movement patterns, frequency, intensity and duration. Measurements included reaction time (RT), Stroop Test (versions 1-3), Letter Cancellation Test (LCT), Trail Making Test (TMT), Trail Walking Test (TWT) and Fitts task (difficulty level 1-4). Data were analyzed using mixed-design ANOVAs. RESULTS:Improvements were observed in Stroop reading (F(1,53) = 14.84, p < .001, η2 = 0.219), Stroop inhibition (F(1,53) = 10.99, p = .002, η2 = 0.172), and LCT (F(1,53) = 4.57, p = .037, η2 = 0.079). A time × group interaction was found for TMT (F(1,53) = 6.55, p = .031, η2 = 0.110), indicating greater changes following VR training. Both groups improved cognitive-motor performance (TWT: F(1,25) = 55.32, p < .001, η2 = 0.689; Fitts3: F(1,53) = 44.97, p < .001, η2 = 0.459), with greater gains for VR in Fitts3 (p = .006). CONCLUSION(S):Eight weeks of VR and SFV enhanced cognitive and cognitive-motor performance. VR provided domain-specific advantages in executive function, but these effects were not uniformly persistent. SFV sustained more improvements in real-world-relevant cognitive-motor tasks.
BACKGROUND:Clear cell renal cell carcinoma (ccRCC) exhibits heterogeneous postoperative outcomes. This study aimed to evaluate systemic immunoinflammatory biomarkers and pathological features and develop an integrated prognostic model for overall survival (OS) in patients with ccRCC. METHODS:This multicenter retrospective study initially screened 1,662 patients who underwent surgery between January 2010 and December 2024. After excluding 27 patients with substantial missing data, 1,635 were included in baseline analyses, of whom 1,429 with complete data were included in prognostic modeling. Candidate predictors identified by univariable Cox regression were selected using elastic net regression and subsequently evaluated by multivariable Cox regression. Model performance was assessed using the C-index, time-dependent area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS:Sixteen variables with p < 0.20 in univariable analyses were considered candidate predictors, and 12 were retained by elastic net regression. ISUP grade, tumor necrosis, platelet count, recurrence/metastasis status, and systemic inflammation response index (SIRI) were independently associated with OS. The nomogram showed good discrimination, with C-indices of 0.849 and 0.869 in the training and internal testing cohorts, respectively. The 1-, 3-, and 5-year AUCs ranged from 0.829 to 0.897. Calibration was satisfactory, and risk stratification identified groups with significantly different survival outcomes (p < 0.001). CONCLUSIONS:An internally evaluated nomogram integrating systemic inflammatory indices and pathological features demonstrated good prognostic performance for OS in patients with ccRCC.
