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Low to moderate alcohol consumption across two decades and subclinical atherosclerosis at age 60: findings from the Northern Sweden Västerbotten Intervention Programme—visualisation of atherosclerosis (VIPVIZA) study
No full textBackgroundAlcohol consumption at low to moderate levels has long been debated in relation to cardiovascular risk, with inconsistent findings. Multi-decade cohort data with repeated exposure assessments are rare, especially in a northern Scandinavian population. This study aims to investigate associations between alcohol consumption at age 40, 50, and 60 and markers of subclinical atherosclerosis [carotid plaque and intima-media thickness (IMT)] at age 60 in a healthy below-risk-threshold alcohol-consuming cohort in Northern Sweden.MethodsParticipants in the Visualisation of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention (VIPVIZA) trial, aged 60 and with alcohol data from the Västerbotten Intervention Programme (VIP) at 40, 50, and 60, with below-risk-threshold alcohol consumption (>0 to ≤100 g/week) (n = 1,014) were included. Alcohol intake data were collected via a food frequency questionnaire in VIP. Carotid plaque and IMT were assessed at age 60 at VIPVIZA baseline.ResultsMean weekly alcohol consumption for the study period was 26 g (±21.4 g), higher in men (37.5 ± 23.8 g) than in women (19.2 ± 16.3 g) and increasing over time in both sexes. At age 60, 49.6% had carotid plaque, and mean IMT was 0.77 mm (±0.15). No indication of associations was found between midlife alcohol consumption and carotid plaque in the total cohort [odds ratio (OR): 1.00, 95% confidence interval (CI): 0.99–1.01], men (OR: 1.00, 95% CI: 0.99–1.01), or women (OR: 0.99, 95% CI: 0.99–1.00) per gram increase of weekly alcohol intake. No associations were observed across consumption groups (>25 to ≤50, >50 to ≤75, >75 to ≤100 vs. >0 to ≤25 g/week).ConclusionNo association was found between self-reported midlife alcohol consumption and subclinical atherosclerosis at age 60 in the VIPVIZA baseline cohort. Results were consistent across sexes and intake levels, contributing to the evidence base used to guide primary prevention and public health recommendations
Meta-analysis of the effects of probiotic supplementation on bone turnover markers in middle-aged and elderly patients with osteoporosis
No full textBackgroundOsteoporosis is highly prevalent among postmenopausal women and is characterized by a progressive 1–2% annual decline in bone mineral density (BMD). This deterioration contributes to more than 8.9 million fractures globally each year. The condition arises from an imbalance between bone formation and resorption. Emerging evidence suggests that probiotics may positively modulate bone metabolism through gut microbiota regulation, yet high-quality clinical data directly linking probiotic use to bone turnover markers remains limited. This meta-analysis investigates the effects of probiotic supplementation on bone formation and resorption markers in osteoporotic individuals.MethodsA systematic review and meta-analysis were conducted on 15 randomized controlled trials (RCTs) involving 1,432 participants. The studies assessed various probiotic strains, dosages, and intervention periods ranging from 8 weeks to 12 months. Pooled effect sizes were calculated for key bone formation markers—procollagen type 1 N-terminal propeptide (P1NP) and osteocalcin—and resorption markers, including C-terminal telopeptide of type I collagen (CTX-I), N-terminal telopeptide (NTX), and tartrate-resistant acid phosphatase 5b (TRAP-5b). Subgroup and dose–response analyses were also performed.ResultsProbiotic supplementation significantly improved bone metabolism. Bone formation markers showed notable increases, including a significant rise in P1NP (MD = +8.4 μg/L; 95% CI: 3.1–13.7) and osteocalcin. Bone resorption markers, especially CTX-I, demonstrated significant reductions (SMD = −0.35; 95% CI: −0.52 to −0.18). Multi-strain probiotic formulations produced greater improvements in both bone formation and resorption compared with single-strain interventions. A clear dose–response trend was observed, with higher probiotic doses correlating with stronger increases in P1NP. Subgroup analyses showed that postmenopausal women experienced more pronounced benefits than mixed-gender groups.DiscussionProbiotic supplementation is associated with enhanced bone formation and reduced bone resorption in individuals with osteoporosis. Multi-strain formulations and higher dosages yielded the greatest improvements, particularly among postmenopausal women. These findings support probiotics as a promising adjunctive strategy for improving bone health and potentially reducing fracture risk. However, longer-term trials and strain-specific mechanistic studies are needed to confirm clinical utility
Aligned piezoelectric fibrous scaffolds for prevention of traumatic neuroma formation
No full textPurposeTraumatic neuroma, a painful complication of peripheral nerve injury, arises from disorganized axonal regeneration and chronic inflammation. Existing treatments provide limited relief. This study aimed to evaluate the therapeutic potential of aligned piezoelectric poly (L-lactide) (PLLA) fibrous scaffolds in preventing neuroma formation by promoting nerve regeneration and mitigating inflammatory and pain-related responses.MethodsAligned PLLA fibrous scaffolds were fabricated using electrospinning and characterized for morphology and piezoelectricity. In vitro, Schwann cell proliferation, morphology, and expression of myelination-related genes (Mag, Mbp, Mpz) were assessed. In vivo, a rat sciatic nerve transection model was used to evaluate autotomy behavior, nerve regeneration, inflammatory and pain-related markers (TNF-α, IL-10, SP, c-Fos), and transcriptomic changes.ResultsPLLA scaffolds significantly promoted Schwann cell proliferation and upregulated myelination-related genes in vitro. In vivo, they reduced autotomy scores and suppressed the expression of inflammatory and nociceptive markers. Histological analyses demonstrated enhanced axonal regeneration and myelination, with greater NF200 and S100 expression, thicker myelin sheaths, and improved structural integrity. Transcriptome analysis revealed upregulation of neuroregenerative genes (e.g., Mag, Mpz, Sox10, Egr2) and anti-inflammatory cytokines (e.g., IL-10, TGF-β), alongside downregulation of proinflammatory and pain-associated genes (e.g., SP, c-Fos, Mmp9, Tnf-α).ConclusionAligned piezoelectric PLLA fibrous scaffolds facilitate functional nerve regeneration, promote remyelination, and attenuate neuropathic pain and inflammation. These findings suggest that such scaffolds offer a promising nanomedicine-based strategy for the prevention of traumatic neuroma following peripheral nerve injury
High mortality and mechanical ventilation in COVID-19-associated pulmonary aspergillosis: insights from a two-center retrospective cohort study
No full textBackgroundStudies on COVID-19-associated pulmonary aspergillosis (CAPA) have raised concerns regarding its high mortality rates. This study aims to assess the mortality of CAPA caused by Alpha and Omicron variants among intensive care unit (ICU) patients in China.MethodsWe enrolled 236 ICU patients admitted to Wuhan Huoshenshan Hospital from 4 January 2020, to 30 March 2022, during the Alpha variant epidemic, and 187 ICU patients admitted to Nanjing Jinling Hospital from 24 October 2022, to 19 January 2023, during the Omicron variant epidemic. We systematically collected clinical data for analysis, and all patients were confirmed to have SARS-CoV-2 infection through polymerase chain reaction (PCR) testing.ResultsThe incidence of CAPA was 5.1% (12/236) during the Alpha variant period and increased to 7.5% (14/187) during the Omicron variant period. The mortality rate among CAPA cases was 33.3% (4/12) for patients infected with the Alpha variant and 28.6% (4/14) for those infected with the Omicron variant. Both rates were higher than the mortality rates among patients without CAPA, which were 4.9% (11/224) during the Alpha period and 8.7% (15/173) during the Omicron period. Mechanical ventilation in CAPA patients requires careful consideration. Aspergillus fumigatus was the most commonly identified causative agent in CAPA cases, while Aspergillus flavus was found in only one case.ConclusionOur findings emphasize the necessity of implementing more effective mycological detection methods and promoting internationally recognized diagnostic criteria for CAPA
Predictive value of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio for three-year survival in patients with early esophageal cancer undergoing endoscopic submucosal dissection
No full textBackgroundEndoscopic submucosal dissection (ESD) has been widely applied as an effective treatment for early esophageal cancer. However, long-term prognosis after surgery remains highly variable. This study aimed to evaluate the clinical value of NLR, PLR, and MLR in patients with early esophageal cancer treated with ESD.MethodsA total of 325 patients with early esophageal cancer who underwent ESD were retrospectively included and categorized into survival and death groups based on their three-year postoperative outcomes. Baseline characteristics between groups were compared using univariate analysis. The Cox proportional hazards model was applied to assess the associations of NLR, PLR, MLR, and their interactions with three-year survival. Restricted cubic spline (RCS) regression was performed to explore the potential nonlinear relationships between NLR, PLR, MLR, and survival outcomes. Receiver operating characteristic (ROC) curves were used to evaluate the predictive ability of NLR, PLR, and MLR for three-year survival.ResultsBaseline characteristics were significantly better in the survival group compared with the death group. The Cox proportional hazards model revealed that higher discharge levels of NLR, PLR, and MLR were significantly associated with increased risk of three-year mortality, with notable synergistic effects observed with tumor location, depth of invasion, tumor size, and margin status. RCS analysis demonstrated significant linear or near-linear associations between NLR, PLR, MLR, and mortality risk. ROC curve analysis indicated that NLR, PLR, and MLR exhibited good predictive performance for three-year survival, with PLR showing superior predictive ability.ConclusionNLR, PLR, and MLR are significantly and positively associated with three-year mortality risk in patients with early esophageal cancer undergoing ESD, in either linear or near-linear patterns. These markers also exhibit synergistic interactions with tumor-related clinical features such as location, depth of invasion, and margin status. Among them, PLR demonstrated the best predictive performance. This study provides valuable evidence for postoperative risk assessment and individualized follow-up management in early esophageal cancer patients
Pharmacovigilance insights: safety profiles of antifungal agents for invasive aspergillosis
No full textBackgroundInvasive aspergillosis (IA) poses significant mortality risks, particularly in immunocompromised patients. The safety profiles of FDA-approved antifungal agents, triazoles (Voriconazole, Posaconazole, Isavuconazole), polyenes (Amphotericin B), and echinocandins (Caspofungin), are not yet fully characterized in real-world settings. This study employed pharmacovigilance data to systematically evaluate the comparative safety profiles of these agents, providing evidence-based insights for clinical practice.MethodsA retrospective analysis of the FDA Adverse Event Reporting System (FAERS) data (2004Q1–2024Q3) was conducted. Disproportionality analyses, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS), were employed to identify adverse event (AE) signals. Duplicate entries were identified and removed using CASE_ID and FDA_DT criteria, after which AE signals were classified according to MedDRA System Organ Classes (SOCs) and Preferred Terms (PTs).ResultsAmong 26,004 antifungal-associated AE reports, Amphotericin B exhibited the strongest renal toxicity signals (nephropathy toxic (i.e., nephrotoxicity): ROR = 24.86; renal tubular disorder: ROR = 46.46), while voriconazole was associated with hepatobiliary disorders (ROR = 4.61) and ocular toxicity (toxic optic neuropathy: ROR = 228.80). Caspofungin demonstrated marked hepatotoxicity (cholestasis: ROR = 23.79), whereas Posaconazole and Isavuconazole showed lower mortality rates (19.56% and 22.70%, respectively). Amphotericin B demonstrated the highest mortality rate (47.14%), which was statistically significantly higher compared to other agents (χ2 test, p < 0.001), and life-threatening AE rates (4.97%), contrasting with Isavuconazole’s favorable safety profile (1.89% life-threatening AEs). Time-to-onset analysis revealed delayed AE onset for Isavuconazole (median: 19.5 days) versus Caspofungin (6 days).ConclusionSignificant safety variations exist among antifungal agents for IA. Amphotericin B and Caspofungin are associated with severe renal/hepatic toxicities and higher mortality, while Isavuconazole and Posaconazole may offer safer alternatives with delayed AE onset. Clinicians should prioritize drug-specific risks when tailoring treatment for IA patients
Biomechanics-based analysis of technical characteristics in skeleton start and specific physical training strategies
No full textPurposeThis study employed kinematic and kinetic testing to analyze the sport-specific parameters of the skeleton start, thereby elucidating its technical characteristics and establishing an empirical basis for training.MethodsSpatiotemporal parameters were captured using a 3D motion system, while ground reaction forces, impulses, and plantar pressure distribution were collected via a Ki-Sprint force platform and custom pressure sensors. Statistical analysis employed descriptive statistics, two-way ANOVA to evaluate factor effects, and appropriate parametric or non-parametric tests for group comparisons.ResultsAthletes’ average starting distance was 18.45 ± 2.09 m, achieved in 12.20 ± 1.11 steps, with no gender difference. Starting speed (male: 6.97 ± 0.42 m/s, female: 6.25 ± 0.58 m/s) and acceleration range (male: 3.31–6.26 m/s2, female: 2.14–5.96 m/s2) differed significantly by gender. Step length differed between push-off (1.60 ± 0.14 m) and follow-up steps (2.09 ± 0.18 m), and between inner (2.60 ± 0.14 m, 0.44 ± 0.03 s) and outer steps (2.64 ± 0.13 m, 0.45 ± 0.03 s) in both length and duration. Take-off (2.71 ± 0.50 m) and preceding step (2.81 ± 0.58 m) lengths did not differ. The maximum horizontal force was 826.99 ± 217.18 N and average horizontal impulse was 264.43 ± 67.64 N·s, neither correlating with front-rear foot spacing. Average plantar pressure was higher during run-up (1.77 ± 0.76 kg/cm2) than take-off (1.19 ± 0.59 kg/cm2).ConclusionThe skeleton start is characterized by periodic speed-power movements akin to a hybrid of sprint acceleration and diving. Training should integrate regular sprints, specialized push simulations, and downhill sprinting to improve acceleration and maximal speed. Core stability, lower-limb maximal strength, and multi-joint power training should be implemented with consideration for gender-specific adaptations
EBUS-TBNA needle rinse fluid: a superior specimen for the molecular diagnosis of intrathoracic lymph node tuberculosis
No full textObjectivesTo evaluate EBUS-TBNA needle rinse fluid versus biopsy tissue for molecular diagnosis of intrathoracic lymph node tuberculosis (TB).MethodsRetrospective analysis of 63 patients with intrathoracic lymph node TB undergoing EBUS-TBNA (2018–2024). Rinse fluid and biopsy tissue were tested via TB-DNA (n=32) and Xpert MTB/RIF (n=31); positivity rates compared.ResultsThe study cohort had a median age of 31 years (interquartile range: 25–50.1 years), with 57.1% (36/63) being male. The most frequently sampled lymph node stations were subcarinal (station 7, 82.5%) and right lower mediastinal (station 4R, 66.7%). Clinically, 82.5% (52/63) of patients had concomitant pulmonary TB, while 17.5% (11/63) presented with isolated intrathoracic lymph node TB. For TB-DNA detection, the positivity rate of rinse fluid (71.9%, 23/32) was significantly higher than that of biopsy tissue (46.9%, 15/32; χ²=4.146, P = 0.042). Similarly, the Xpert MTB/RIF assay showed a higher positivity rate in rinse fluid (77.4%, 24/31) compared to tissue (41.9%, 13/31; χ²=8.11, P = 0.004).ConclusionsEBUS-TBNA rinse fluid demonstrates higher sensitivity than biopsy tissue for intrathoracic lymph node TB via TB-DNA/Xpert MTB/RIF. Routine rinse fluid testing improves diagnostic yield
Efficacy and safety of Traditional Chinese Medicine injections for no-reflow or slow flow in patients with acute coronary syndrome after percutaneous coronary intervention: a systematic review and network meta-analysis
No full textIntroduction: There is a possibility of ischemia-reperfusion injury following percutaneous coronary intervention (PCI). Traditional Chinese medicine (TCM) treatment features multi-target and multi-link interventions, along with relatively good safety profiles, making it a promising option for alleviating ischemia-reperfusion injury following PCI.MethodsWe searched the China National Knowledge Infrastructure (CNKI), VIP Journal Database, China Biomedical Literature Database, Wanfang Medical Database, PubMed, Web of Science, Embase, and Cochrane Library for randomized controlled trials published in Chinese and English regarding Chinese herbal injections for treating no-reflow or slow-reflow after PCI, from database inception to November 30, 2024.ResultsA total of 14 interventions were evaluated, involving 5,535 patients. The interventions encompassed 14 types, including Shenfu Injection, Ginseng Injection, Shengmai Injection, Tanshinone IIA Sodium Sulfonate Injection, Danhong Injection, Danshen Injection, Shuxuetong Injection, Tanshinone Injection, Salvianolate Lyophilized Injection, Xuesaitong Injection, Salvia Ligustrazine Injection, Ixeris Sonchifolia Injection, Ginkgo Damo Injection, and standard treatment. The results indicated that the combination of salvianolate lyophilized injection with standard treatment might provide the best efficacy in improving no-reflow or slow blood flow after PCI. For enhancing Left Ventricular Ejection Fraction (LVEF) and reducing Left Ventricular End-Diastolic Dimension (LVEDD), the effect of Danshen Injection combined with standard Western medicine treatment was the most significant. Regarding reducing Left Ventricular End-Systolic Diameter (LVESD) and decreasing the incidence of Major Adverse Cardiovascular Events (MACE), Shenfu Injection showed possibly the most ideal effect. Meanwhile, Danhong Injection combined with standard treatment significantly improved the incidence of no-reflow compared to standard treatment, while also exhibiting positive effects on LVEF, reducing LVESD, and effectively decreasing the occurrence of MACE.ConclusionTraditional Chinese Medicine (TCM) injections demonstrate significant efficacy and a favorable safety profile in treating no-reflow or slow blood flow after PCI in patients with acute coronary syndrome.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42024497449, PROSPERO CRD42024497449
Whole-genome identification of LdELF4s and analysis of their expression response to diurnal temperature variations in Lilium davidii var. willmottiae (E. H. Wilson) raffill
No full textIntroductionLanzhou lily (Lilium davidii var. willmottiae), a medicinal and edible plant endemic to China, synthesizes bioactive compounds regulated by diurnal temperature variations (DIFs). ELF4 family genes, key regulators coordinating endogenous rhythms with external changes, are unexplored in this species.MethodsWe analyzed nuclear–cytoplasmic phylogeny across 11 species and identified ELF4 homologs. Phylogenetic, collinearity, cis-element, and expression pattern analyses were conducted for Lanzhou lily ELF4s (LdELF4s). qRT–PCR assessed LdELF4 expression under different DIFs (20/20°C, 25/10°C, 20/5°C day/night), and corresponding phenotypes were evaluated.ResultsCytonuclear discordance was observed within Lilium. 62 ELF4 homologs were identified and classified into four subfamilies. Six LdELF4s were located on chromosomes LG01, LG08, LG09, LG12, showing structural variation compared to Lilium sargentiae. LdELF4.1, LdELF4.3, and LdELF4.6 were significantly upregulated at 25/10°C on day 14, while LdELF4.4 and LdELF4.5 were downregulated at 20/5°C. LdELF4.6 showed highest sensitivity. Phenotypically, 25/10°C and 20/5°C treatments delayed flowering by 12.5 and 7.8 days, respectively. The 25/10°C treatment increased stem diameter but reduced flower bud number.Discussion/ConclusionLdELF4.6 is a core candidate gene regulating DIF response in Lanzhou lily, with 25/10°C potentially optimal for bulb development. This study provides genetic resources for breeding climate-adaptive lilies
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