by Xuying Zhang, Johanna Mainzer, Isabella Giambra, Tong Yin, Petra Engel, Hannah Hümmelchen, Henrik Wagner, Axel Wehrend, Christiane Egerer, Katharina Gerhards, Gerald Reiner, Sven König
Long tails trigger tail biting in pigs and increase the risk of flystrike infections in sheep. Tail docking has been a common management practice in both species for decades, but increasingly conflicts with legal animal welfare guidelines. Sustainable solutions require breeding strategies targeting shorter tails. In consequence, the aims were to conduct whole-genome sequencing (WGS)-based genome-wide association studies (GWAS) and comparative genomic analyses (CGA) to explore functional elements influencing tail traits. Phenotypically divergent experimental populations of pigs and sheep were established through unified selection and mating experiments. Tail traits included tail length (TL) measured at birth, and tail abnormalities (TA) assessed radiographically at 14 weeks of age. WGS-based GWAS identified a significant locus on SSC18 in pigs and suggestive loci for TL in both species, which, together with previously reported loci for TA, were further analyzed by CGA. The genomic windows of the significant locus on SSC18 in pigs and the TL GWAS locus on OAR4 in sheep were found to be conserved, harboring six common genes with predicted functional variants. These variants were jointly associated with TL (Plm ) in both species in linear regression models adjusted for sex, age of the dam, body length, and body weight. In other GWAS locus windows (±1 Mb), species-specific TL candidate genes were identified in sheep (HOXB13, MUC5B, EPB41L3, MTCL1, PIEZO2, MPPE1, and LOXHD1) and in pigs (KNL1, DISP2, SPRED1, TGFB2, and HAND1), each harboring associated putative functional variants. For TA, sheep-specific candidates (PGM2, LRRC66, CRACD, LOC105601916, and SH2D4B) and pig-specific candidates (MYOT, TMCO6, and PCDHAC2) were revealed using logistic regression models (Pglm ). GO analyses of candidate genes predicted shared biological processes between sheep and pigs, whereas pathway analyses indicated that common carbohydrate metabolism pathways, along with species-specific immune and inflammatory signaling, and pig-specific TGF-β signaling and endochondral ossification, may contribute to tail length variation and abnormalities. These findings provided deeper insights into the genetic basis of differential embryonic tail morphogenesis and perinatal tail development across species.by Xiangxiang Kong, Lujie Karen Chen, Sancharee Hom Chowdhurry, Ryan B. Felix, Shiming Yang, Peter Hu, Neeraj Badjatia, Jamie Erin Podell
Paroxysmal sympathetic hyperactivity (PSH) is a syndrome that occurs in a large subset of critically ill traumatic brain injury (TBI) patients and is associated with complications and poor recovery. PSH is defined by recurrent episodic vital sign elevations in the appropriate clinical context. However, standard diagnostic criteria rely heavily on subjective judgment, leading to challenges and delays in recognition, monitoring, and management. The objective of this study was to develop automated PSH detection and quantification tools that exclusively utilize objective bedside continuous vital sign data. Using a cohort of 221 critically ill acute TBI patients with at least 14 days of continuous physiologic data (of which 107 were clinically diagnosed with PSH) we developed a high-resolution clinical feature scale based on established PSH-Assessment Measure criteria and two artificial intelligence-based episode detection models including an expert system approach and a machine learning model approach, using a clinician-annotated case example as ground truth. For the episode detection methods, PSH was quantified as the number, duration, and overall temporal burden of detected episodes. To evaluate performance, we compared quantifications across PSH cases and controls and explored precision and recall. All three methods demonstrated initial face validity to delineate PSH cases from non-PSH TBI controls. Future optimization and implementation of the described computational frameworks with real-time patient data could improve the standard monitoring and management of this challenging clinical syndrome.by Yaosen Du, Yiyong Yang, Xiaolong Wu, Pengju Gao, Hanchen Ma
To enhance the efficiency, safety, and data accuracy of drilling engineering, this study developed an integrated business management platform for drilling engineering grassroots units based on the Business Model Driven (BMD) approach. The platform is built on a “five horizontal, three vertical” cloud computing architecture, establishing a five-layer system from the infrastructure layer to the user layer horizontally, and supported by standard specifications, safety, and maintenance systems vertically, enabling collaboration across multiple business scenarios and data integration. Currently, four major modules with over 20 functionalities have been developed, supporting applications such as task coordination, engineering supervision, data analysis, and accident handling. Operational results demonstrate that the platform effectively promotes integrated management of drilling engineering through real-time data sharing, full-process quality control, and intelligent decision-making, thereby enhancing operational quality and safety, reducing accident risks, and providing critical technological support for the digital transformation and upgrading of the drilling industry.by Peiling Zuo, Huanhuan Zhu, Chunying Sun, Xiaohan Ma, Sheng Chen, Rong Tang, Tong Wu, Ding Zhang, Xiao Tang, Wenquan Lv, Wenzhong Chen, Xiawei Wei, Encun Hou, Minsheng Wu, Minghe Jiang
BackgroundEvidence indicates that the Endothelial Activation and Stress Index (EASIX) is a predictor of mortality in endothelium-related conditions; however, its association with mortality risk in atrial fibrillation (AF) remains uncertain. Accordingly, this study examines the relationship between EASIX and mortality risk among patients with AF.
MethodsThis retrospective analysis utilized data from the Medical Information Marketplace in Intensive Care IV (MIMIC-IV) database, which includes critically ill patients diagnosed with AF. To examine the association between EASIX scores and mortality, Kaplan–Meier survival analysis, Cox proportional hazards models, and restricted cubic spline regression were applied to evaluate the relationship between EASIX and all-cause mortality. Subgroup analyses were conducted to explore potential interactions with key patient characteristics, and sensitivity analyses were performed to further confirm the robustness of the results.
ResultsA total of 3,193 patients were included in the analysis. KM survival analysis showed that elevated EASIX levels were associated with a higher risk of both in-hospital and ICU mortality. After adjusting for potential confounders, increased EASIX levels remained significantly associated with in-hospital mortality [HR, 1.09 (95% CI 1.03, 1.15), P = 0.0002] and ICU mortality [HR, 1.10 (95% CI 1.04, 1.17), P = 0.0002]. Stratified analyses revealed a significant interaction between sepsis, respiratory failure, and EASIX in relation to both in-hospital and ICU mortality. To evaluate the robustness of the findings, a sensitivity analysis was performed. After additionally adjusting for metoprolol and heparin as covariates, patients in the highest EASIX group continued to demonstrate the greatest mortality risk: the HR for in-hospital death was 2.08 (95% CI: 1.51–2.85), and the HR for ICU death was 1.83 (95% CI: 1.21–2.65).
ConclusionElevated EASIX levels correlate with higher mortality rates, underscoring its potential as an accessible tool for identifying high-risk patients and informing clinical decisions. However, further studies are needed to explore the underlying mechanisms and validate its applicability across diverse patient populations.
by Ruyi Li, Shaoping Jiang, Zhaoke Pi, Guisu Chen
Pathological and neuroimaging changes in the cerebellum of Alzheimer’s disease (AD) patients have been well documented. However, the changes in cerebellar amyloid plaque deposition connectivity networks during AD progression based on positron emission tomography (PET) imaging remain unclear. We selected 18F-florbetapir PET (18F-AV45 PET) imaging data from the Alzheimer’s disease neuroimaging initiative (ADNI) dataset (n = 612) and employed graph theoretical analysis to examine amyloid plaque deposition connectivity, comparing the connectivity differences across cognitively normal (CN), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and AD groups. In addition, we combined graph theoretical features with the standardized uptake value ratio (SUVR) of regions of interest and applied them to machine learning models for the early diagnosis of AD. As cognitive decline progressed, significant changes in cerebellar network connectivity were observed across groups. Regarding local connectivity, changes in betweenness centrality were evident in multiple cerebellar regions at different cognitive stages. Cerebellar amyloid networks revealed early changes in amyloid plaque deposition connectivity. The machine learning model achieved an area under the curve (AUC) of 0.950 for distinguishing AD from CN, 0.995 for CN vs. EMCI, 0.964 for EMCI vs. LMCI and 0.632 for LMCI vs. AD. These findings provide new insights into the cerebellar pathological features of AD and highlight the potential of this approach for early identification and prediction of AD progression.by Achilleas Livieratos, Maria Kudela, Yuxi Zhao, All-shine Chen, Xin Luo, Junjing Lin, Di Zhang, Sai Dharmarajan, Sotirios Tsiodras, Vivek Rudrapatna, Margaret Gamalo
BackgroundNetwork meta-analysis (NMA) can compare several interventions at once by combining head-to-head and indirect trial evidence. However, identifying, extracting, and modelling these often takes months, delaying updates in many therapeutic areas.
ObjectiveTo develop and validate MetaMind, an end-to-end, transformer-driven framework that automates NMA processes—including study retrieval, structured data extraction, and meta-analysis execution—while minimizing human input.
MethodsMetaMind integrates Promptriever, a fine-tuned retrieval model, to semantically retrieve high-impact clinical trials from PubMed; a multi-agent LLM architecture--Mixture of Agents (MoA)-- pipeline to extract PICO-structured (Population, Intervention, Comparison, Outcome) endpoints; and GPT-4o–generated Python and R scripts to perform Bayesian random-effects NMA and other NMA designs within a unified workflow. Validation was conducted by comparing MetaMind’s outputs against manually performed NMAs in ulcerative colitis (UC) and Crohn’s disease (CD).
ResultsPromptriever outperformed baseline SentenceTransformer with higher similarity scores (0.7403 vs. 0.7049 for UC; 0.7142 vs. 0.7049 for CD) and narrower relevance ranges. Promptriever performance achieved 82.1% recall, 91.1% precision and an F1 score of 86.4% when compared to a previously published NMA. MetaMind achieved 100% accuracy on a limited set of remission endpoints regarding PICO (Population, Intervention, Comparator, Outcome) element extraction and produced comparative effect estimates and credible intervals closely matching manual analyses.
ConclusionsIn our validation studies, MetaMind reduced the end-to-end NMA process to less than a week, compared with the several months typically needed for manual workflows, while preserving statistical rigor. This suggests its potential for future scaling of evidence synthesis to additional therapeutic areas.
by Erschena Reichle, Martin Frei-Erb, Sven Streit
The shortage of general practitioners (GPs) and the aging workforce of established GPs in Switzerland are persistent. Furthermore, data on GPs with additional training in complementary medicine (CM) are lacking. This study aimed to obtain information on GPs with training in CM. A nationwide cross-sectional study was conducted using an anonymous online survey to assess the demographics, practice structures, workloads, and future perspectives. The participants were members of four CM societies representing doctors with CM certificates (n = 1,067) in traditional Chinese medicine/acupuncture (TCM/A), homeopathy (HOM), anthroposophical medicine, and phytotherapy. Overall, 206 GPs were included and divided into three groups: TCM/A (n = 73), HOM (n = 76), and others (n = 57). Most participants were male, and approximately half worked in double or group practices. They worked an average of 36 h per week, which had decreased by 13 h over the past 5 years, with plans for further reduction in the future. Approximately 18% planned to continue working beyond the retirement age, and 4% wanted to retire before that age. The majority expressed optimism about the future of CM in Swiss healthcare but less for individual CM disciplines. Compared to the 2015 Swiss Workforce Study, more CM GPs were female, worked less often in group practices, made fewer house calls, and were more optimistic about the future. CM-GPs in Switzerland face the same challenges as conventional GPs. National action and collaboration are needed to improve working conditions and to address the trend towards part-time work and an ageing workforce to safeguard healthcare for the population.by Ran Chen, Yan Sun, Wenlin Tai
BackgroundPrimary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by cholestasis caused by intrahepatic small bile duct injury. Promoting the molecular mechanism of OTU deubiquitinase 5 (OTUD5) in the treatment of PBC requires further exploration. This study unraveled the molecular underpinnings of PBC through bio-informatics analysis and experimental verification for the development of targeted therapeutic strategies.
MethodsThis study screened immune-related genes and validated their expression patterns in whole blood of patients with PBC using microarray based on GEO datasets. The expression level of OTU deubiquitinase 5 (OTUD5) was validated in peripheral blood samples using RT-qPCR and immunofluorescence. Subsequently, proteomic bioinformatics analyses were conducted utilizing STRING and InBio Discover databases to predict interactions with the mitochondrial antiviral signalling protein (MAVS). Furthermore, immunochemical and immunofluorescence analyses of MAVS expression in liver tissues were conducted with a thorough analysis of immune cell infiltration specific to the disease by utilizing single-cell RNA sequencing (scRNA-seq) technology in peripheral blood mononuclear cells (PBMCs) derived from both patients with PBC and healthy controls.
ResultsCompared with those of healthy controls, the liver tissues of patients with PBC presented increased NK cell activation, monocyte/mast cell numbers, and eosinophil numbers. Compared with those in 10 healthy controls, the expression of OTUD5 and MAVS was increased in 16 tissues of patients with PBC. High expression of OTUD5-MAVS in subpopulation 11 mononuclear macrophages was screened by PBMC scRNA-seq, and mononuclear cells with the subgroup 11 phenotype presented highly differentiated characteristics. The expression of OTUD5 and MAVS was inhibited in RAW264.7 cells when OTUD5 was knocked down (P Conclusion
This study focused on the overexpression of OTUD5 and its interaction with MAVS within macrophage subset 11 in patients with primary biliary cholangitis (PBC). The expression of OTUD5 and MAVS is increased in patients with PBC and is a potential target for the diagnosis and treatment of PBC.
by Fang-Yi Chen, Chin-Chu Chen, Chuan-Chin Chiao
The regenerative capacity of mammalian RGC neurites after damage, such as glaucoma, is limited. Numerous studies have utilized herbal extracts to promote neural regeneration and exert neuroprotective effects in the hope of mitigating glaucoma. In the present study, we investigated the effect of extracts from the cicada fungus (Cordyceps cicadae) and the Lion’s mane mushroom (Hericium erinaceus) on neurite outgrowth of retinal explants and isolated RGCs. We also examined whether these extracts affect the number of apoptotic cells and neurite outgrowth activity of RGCs. The results showed that an aqueous extract of Cordyceps cicadae, an ethanol extract of Hericium erinaceus, and the purified compound Erinacine Sare able to promote neurite outgrowth in retinal explants. Given its role as a key bioactive compound, Erinacine S was further investigated on isolated RGCs, where it also significantly enhanced neurite outgrowth, demonstrating a direct effect on RGC regeneration. In addition, these extracts have no significant drawbacks in terms of cell apoptosis and RGC neurite outgrowth activity at specific concentrations. The present study thus demonstrates that while excessively high concentrations of these extracts may inhibit neurite growth, at moderate concentrations some extracts from Cordyceps cicadae and Hericium erinaceus have the potential of promoting neurite regeneration in the mammalian retina. Further research targeting the molecular mechanisms behind these effects may shed light on their potential application as a medicine or nutraceutical for facilitating neural regeneration.by Chao Feng, Guodong Chen, Yan Shu, Jing Chen, Wenxin Ye, Ligang Ren
IntroductionGiven the high recurrence rate of bladder cancer (BCa) and the significant adverse effects associated with conventional treatments, it is urgent to search for new clinical therapeutic targets and safer natural-derived compounds. Resveratrol (Res) has been demonstrated to exhibit cytotoxicity against various tumors. However, the signaling pathways and targets involved in inhibition of BCa cells still need further exploration. This study aims to investigate the mechanism of Res in Bca via suppression of the AURKA/STAT3 axis, providing important theoretical basis for subsequent further researches on Res for treating BCa.
MethodsDifferentially expressed genes were identified through bioinformatics methods and the binding sites of resveratrol were also identified. The cell survival rate was detected by the CCK8 method to calculate the concentrations of Res for 30% inhibition and for 50% inhibition. Then, flow cytometry was used to detect the cell cycle and apoptosis after treatment with different concentrations of Res. Immunofluorescence staining was used to detect the effects of Res and MLN8237 on the expression of STAT3. Western blot and qPCR analyses were used to verify the reliability of the effects of Res and MLN8237 on target proteins.
ResultsAURKA was identified as the potential target of Res by computational analysis. Further validation through CCK8 assays and flow cytometry demonstrated that Res could inhibit BCa cells and their cell cycle in a time- and dose-dependent manner. Immunofluorescence staining revealed both Res and MLN8237 suppressed STAT3 expression in BCa cells. Additionally, western blot and qPCR analysis confirmed that Res and MLN8237 inhibited the expression of AURKA and known target genes (VEGF, Bcl-2, and Cyclin D1).
ConclusionOur findings suggest that Res may regulate BCa cell expression through the AURKA/STAT3 axis, providing a theoretical foundation for the structural optimization of Res and the development of multi-target drugs for clinical application.
by Kexuan Chen, Sarah Miller, Kristine Goy, Tina Lam, Marlène Maeusli, Rosemary She, Brad Spellberg, Brian Luna
Metallo-β-lactamases (MBLs) hydrolyze the beta-lactam ring in beta-lactam antibiotics, rendering them ineffective. Infections caused by MBL-harboring bacteria result in higher mortality, more costs and prolonged hospital stays due to the limited treatment options. Recently, antimicrobial susceptibility testing using RPMI-1640 has been found to have more accuracy in predicting in vivo efficacy due to its zinc deficiency. We sought to expand the previous studies of accessing in vivo efficacy using zinc-limited media versus conventional media to more antimicrobial agents and MBL-producing strains. The susceptibility of isolates was determined by performing minimum inhibitory concentration (MIC) assays using traditional cation-adjusted Mueller Hinton broth (CAMHB) or zinc-limited media. In vivo outcomes were evaluated using the Galleria mellonella infection model and neutropenic mouse thigh infection model. The MICs of MBL-harboring strains decreased in zinc-limited media compared to in nutrient-rich media, suggesting susceptibility of a subset of resistant strains when tested in zinc-limited media. Notably, we observed statistically significant MICs decreasing against imipenem, which demonstrated the best efficacy among the six tested antibiotics. Additionally, the outcomes of in vivo tests in both the G. mellonella model and the mouse model were better predicted with in vitro MIC assays performing in zinc-limited media. The use of zinc-limited media may lead to increased accuracy of the prediction of in vivo efficacy of beta-lactams against MBL-harboring bacteria.by Ernest V. Boiko, Elena V. Samkovich, Irina E. Panova, Alexander A. Ivanov, Sergey B. Shevchenko, Sergey L. Vorobyev, Elizaveta S. Kalashnikova, Victoria G. Gvazava, Elizaveta A. Masian, Alexandra E. Kim
PurposeTo define optimal exposure parameters and the therapeutic window for transscleral photodynamic therapy (TSPDT) with chlorin e6 by evaluating clinical, histological, and thermal effects of subthreshold, therapeutic, and suprathreshold settings in rabbit eyes.
MethodsThe study was conducted on 21 healthy rabbits. TSPDT was performed using a 660 nm laser and chlorin e6 (2.5 mg/kg). Transscleral probes (5 mm: 0.1 W, 0.17 W, 0.3 W; 10 mm: 0.3 W, 0.6 W) with integrated thermosensors were used. Enucleation and histological analysis were performed 14 days post-irradiation.
ResultsFundus examination on day 14 revealed distinct treatment zones correlating with laser settings. The therapeutic window was defined as 0.14–0.17 W (5 mm probe; power density: 0.693–0.866 W/cm²; energy density: 415.8–519.6 J/cm²) and 0.48–0.6 W (10 mm probe; 0.611–0.764 W/cm²; 366.6–458.4 J/cm²) with 600 s exposure time, achieving selective choroidal damage without scleral or retinal injury (ΔT ≤ 4.5°C). Suprathreshold settings (≥0.3 W for 5 mm; ≥ 0.6 W for 10 mm) induced retinal necrosis (up to 50%) and scleral coagulation (ΔT ≥ 8°C) with power densities exceeding 0.866 W/cm² (5 mm) and 0.764 W/cm² (10 mm).
ConclusionTSPDT with chlorin e6 enables selective targeting of intraocular pathological tissues while preserving scleral and retinal integrity. Defining the therapeutic window and using real-time thermal monitoring enhances treatment safety. These findings lay a foundation for clinical protocols for uveal melanoma and other intraocular tumors.
by Zihao Li, Xuejiao Chen, Wanli Hu, Gefei Li, Xiaoke Zhang, Datian Gao, Haiyun Gao, Songhe Shi
ObjectiveTo evaluate the longitudinal association between the Metabolic Score for Insulin Resistance (METS-IR) and the risk of diabetes mellitus in rural Chinese adults.
MethodsThis retrospective cohort study included 53,120 participants aged ≥18 years from 2018 to 2023. Participants were stratified by quartiles of the METS-IR metrics. Cox proportional hazards models assessed the association between METS-IR and incident diabetes. Restricted cubic spline (RCS) models examined nonlinear trends. Subgroup analysis, interaction tests, and multiple sensitivity analyses were performed. Predictive ability was evaluated using time-dependent receiver operating characteristic (ROC) curves.
ResultsDuring 176,413.4 person-years of follow-up (median 3.83 years), 14,397 participants developed diabetes. After multifactorial adjustment, METS-IR was significantly and positively associated with diabetes onset (hazard ratio (HR)=1.094,95% confidence interval (CI): 1.076–1.112, P Conclusion
METS-IR is significantly correlated with the onset of diabetes, and the relationship is nonlinear. While it demonstrates limited discriminatory performance as a standalone screening tool, it remains suitable for initial risk stratification in primary health care institutions with limited resources.
by Weiheng Chen, Shouxi Zhu, Kequan Shao, Kejia Liang
To examine the impact of work-family conflict on occupational burnout among pilots following the COVID-19 pandemic, this study employed the Maslach Burnout Inventory-General Survey and the Zhao Xinyuan Bi-directional Scale of Work-Family Conflict as research instruments. The data were analyzed using correlation analysis and Structural Equation Modeling (SEM) to explore the relationship between work-family conflict and burnout. The results indicate a significant correlation between work-family conflict and burnout, as well as the three dimensions of burnout. Specifically, the correlation coefficients between work interfering with family (WIF) and family interfering with work (FIW) with occupational burnout were found to be 0.737 and 0.496, respectively. In the path analysis of the SEM, the estimated effects of WIF and FIW on burnout were both 0.49. Mediation analysis revealed that WIF indirectly influences burnout through FIW, with a mediation effect value of 0.117. Additionally, while pilot-related factors did not significantly affect burnout, they were found to have a notable impact on work-family conflict. These findings underscore the significant role of work-family conflict in contributing to burnout and provide a theoretical foundation for targeted interventions aimed at mitigating burnout among pilots.by Yonggang Chen, Jintai Luo, Yingying Zheng, Xiaomei Jiang, Zixiang Yang, Xiaobing Liu
BackgroundDiabetic kidney disease (DKD) poses a significant health burden with inadequate diagnostic sensitivity. This study develops non-invasive biomarkers by integrating urinary and renal single-cell sequencing with machine learning.
MethodsThis study analyzed DKD single-cell and bulk transcriptomic data from public repositories. We established a computational pipeline to distinguish kidney-originating cells in urinary sediments, enabling the identification of injury-associated gene signatures. These signatures were refined using machine learning to develop a diagnostic model, which was validated in independent cohorts. The biomarkers were further verified in DKD renal tissues at single-cell resolution and across multiple nephropathies. Functional and spatial analyses confirmed biological relevance using transcriptomic and histological validation.
ResultsSingle-cell analysis of 2,089 urine-derived cells identified eight renal cell types, including injured proximal tubule cells (Inj-PTC) showing upregulated injury markers (HAVCR1, VCAM1) and enriched apoptotic/TGF-β pathways. A machine learning-selected biomarker panel (PDK4, RHCG, FBP1) demonstrated strong diagnostic value (area under the curve, AUC > 0.9), with consistent downregulation across multiple chronic kidney diseases. PDK4 and FBP1 were specifically suppressed in DKD renal Inj-PTC (p Conclusions
This study identifies a three-gene biomarker panel (PDK4, RHCG, FBP1) as a promising non-invasive diagnostic tool for DKD. While demonstrating excellent diagnostic performance. It represents a tubular injury-associated gene signature that is detectable in urinary cells and shows strong association with DKD in transcriptomic datasets, presenting a promising candidate for a non-invasive diagnostic assay.
by Yun Feng, Wei Chen, Yang Lu, Haifei Zhou
PurposeThe aim of this study is to evaluate the changes of white matter microstructure in breast cancer patients before and after chemotherapy based on automated fiber quantification (AFQ),as well as determine if these dispersion indexes are significantly correlated with clinical data.
Materials and MethodsTwenty-four breast cancer patients scheduled for chemotherapy were enrolled. Diffusion tensor imaging (DTI), neuropsychological tests and self-report measures, and hematological tests were conducted before chemotherapy(time 0,T0) and within one week after chemotherapy(time 1,T1). AFQ was used to track 20 fiber tracts in the brain. The correlation between average abnormal tracts and changes in neuropsychological tests and self-report measures and blood indicators was analyzed.
ResultsCompared to T0, subjects at T1 showed decreased scores on the verbal fluency test; increased scores on the self-rating anxiety scale(SAS)and self-rating depression scale (SDS). Estrogen concentration was lower while luteinizing hormone(LH), follicle-stimulating hormone, and triglyceride levels were higher. Mean fractional anisotropy (FA) value decreased in the right cingulum cingulate(CGC)while mean radial diffusivity (RD) increased in the right CGC; mean axial diffusivity (AD) value decreased in callosum forceps major and callosum forceps minor. Changes in FA with in the right CGC were positively correlated with changes in SDS and LH, while changes in RD with in the right CGC were negatively correlated with changes in SDS and LH.
ConclusionEarly changes observed in brain white matter fiber tracts, along with persistent hormone and triglyceride metabolism disorders, could potentially serve as neurobiological markers for monitoring chemotherapy-induced cognitive impairment.
by Yinyin Wu, Wei Ding, Yuying Liu, Qianhong Deng, Fengqin Tao, Hanbin Chen, Chang Chen, Meng Xiao, Bilong Feng
BackgroundStandardized guidelines for optimal tunnel length in tunneled peripherally inserted central catheters (PICCs) are lacking.
ObjectivesThe objective of this study was to evaluate the real-world impact of tunnel length on clinical outcomes.
MethodsThis retrospective cohort study included 207 cancer patients who received tunneled PICCs, categorized into a control group (tunnel length > 4 cm, n = 134) and an observation group (tunnel length ≤ 4 cm, n = 73). Propensity score matching (PSM) was used to address baseline heterogeneity. Cox regression analyses were used to assess the risk of complication during a 120-day follow-up.
ResultsCompared to the control group (tunnel length > 4 cm), the observation group (tunnel length ≤ 4 cm) had a significantly higher adjusted overall complication risk (HR = 2.92, 95% CI: 1.07–7.94, P = 0.036) and unplanned catheter removal rate (4.4% vs. 0.0%, P = 0.027), confirming the safety of longer tunnels despite comparable comfort levels between groups. After PSM, Cox regression analysis showed results consistent with those from the unmatched cohort. Subgroup analyses revealed a reduced risk of complications with longer tunnels in patients with BMI ≤ 25 kg/m² (HR = 0.29, 95% CI: 0.11–0.82), without hypertension (HR = 0.36, 95% CI: 0.13–1.00), without diabetes (HR = 0.38, 95% CI: 0.15–0.97), and with solid tumors (HR = 0.31, 95% CI: 0.11–0.85).
ConclusionThe results show that tunnel lengths > 4 cm reduce overall complications and prolong catheter retention, supporting the implementation of standardized protocols while advocating for personalized adjustments based on BMI, comorbidities, and cancer type.
by Lei Guo, Jun Ge, Li Cheng, Xinyi Zhang, Zhengzheng Wu, Meili Liu, Hanmei Jiang, Wei Gong, Yi Liu
BackgroundThe incidence of ulcerative colitis (UC) remains high, with an increasing prevalence among elderly patients. Cellular senescence has been widely recognized as a contributor to UC susceptibility; however, the underlying molecular mechanisms remain incompletely understood. This study aimed to identify senescence-associated biomarkers in UC to provide new insight for diagnosis and treatment.
MethodsBy integrating transcriptomic data from UC patients with established aging-related databases, we identified aging-associated differentially expressed genes (DEGs). Using weighted gene co-expression network analysis (WGCNA) and Cytoscape, we pinpointed the core genes involved. A diagnostic model for UC was then developed based on these core genes, and their expression patterns were characterized at single-cell resolution. The roles of these genes were ultimately validated through in vitro and animal experiments.
ResultsWe identified 24 aging-related DEGs in UC, which were primarily implicated in inflammatory responses and cytokine-receptor interactions. Further analyses pinpointed three core genes (CXCL1, MMP9, and STAT1) that were predominantly expressed in macrophages. A diagnostic model constructed using these genes exhibited robust predictive performance. Experimental validation confirmed that the expression levels of all three core genes were significantly upregulated in both a UC mouse model and in macrophages compared to controls. Additionally, pathway analyses revealed elevated levels of CXCL12 and VEGFA in the enriched pathways.
DiscussionOur findings underscore the pivotal roles of CXCL1, MMP9, and STAT1 in UC-associated cellular senescence. The analysis positions these molecules as promising macrophage-mediated diagnostic biomarkers and therapeutic targets. Collectively, this work provides novel insights into UC pathogenesis and lays a foundation for developing precision medicine strategies that target senescence pathways.
by Bing-Nan Zhao, Zi-Yang Xie, Jia-Ning Liu, Xiao-Ran Chen, Xin-Xin Wang, Jia-Yi Li, Rui Zhang, Chao Si
Fermented spent coffee grounds (FSCG) serve as a valuable soil amendment to improve soil structure and fertility, while earthworms play a well-established role in enhancing soil processes and plant growth. However, their combined effects on bioactive compound accumulation in medicinal plants remain unclear. This study investigated the individual and interactive effects of FSCG (0%, 10%, and 20%, v/v) and earthworms (with and without Pheretima guillelmi) on the growth and phytochemical content of Glechoma longituba, a common medicinal herb, under greenhouse conditions. Results showed that 10% FSCG generally promoted plant growth, whereas 20% FSCG generally enhanced the accumulation of total flavonoids, chlorogenic acid, and soluble protein. Earthworms enhanced aboveground biomass and node number but significantly reduced chlorogenic acid content. These findings highlight the potential of FSCG as a sustainable soil amendment in medicinal plant cultivation and underscore the need to consider earthworm activity when optimizing both plant biomass and phytochemical quality.by Linna Zhao, Juanjuan Zhang, Weizhe Liu, Cheng Dai, Aiying Li
Diabetes mellitus (DM) is identified as a potential modifier of clinical outcomes in acute heart failure (AHF), yet its prognostic impact is not fully determined. This systematic review and meta-analysis aimed to assess the prognostic impact of DM on survival outcomes in AHF patients by synthesizing evidence from 26 studies involving 326,928 subjects collected from Cochrane Library, PubMed, Web of Science, and Embase databases up to 1 June 2024. Both prospective/retrospective cohort and case-control studies published since 2000 were included, with outcomes evaluated through multivariate, univariate, and binary analyses using the Newcastle-Ottawa Scale for quality assessment. Multivariate analysis indicated that DM significantly increased the risk of all-cause mortality in AHF patients (cohort studies: HR = 1.21, 95%CI (1.13, 1.29), OR=1.15, 95%CI (1.05, 1.26); case-control studies: HR = 1.39, 95%CI (1.26, 1.53), OR=1.43, 95%CI (1.10, 1.84)]. Univariate analysis confirmed this finding in case-control studies [HR = 1.30, 95%CI (1.01, 1.67)], but not in cohort studies. In both cohort [RR = 1.27, 95%CI (1.12, 1.43)] and case-control [OR=1.21, 95%CI (1.08, 1.35)] studies, DM increased the risk of all-cause mortality. AHF patients with DM had a higher risk of cardiovascular mortality [cohort studies: HR = 1.85, 95%CI (1.46, 2.33); case-control: OR=1.70, 95%CI (1.17, 2.47)]. While multivariate analysis showed no association between DM and in-hospital mortality, case-control studies indicated an increased risk [OR=1.21, 95%CI (1.03, 1.42)]. DM also increased the risk of readmission [cohort studies: HR = 1.32, 95%CI (1.14, 1.53); case-control studies: HR = 1.44, 95%CI (1.23, 1.69); binary data: OR=1.19, 95%CI (1.07, 1.31)].This updated meta-analysis demonstrates that DM imposes significant adverse effects on all-cause mortality, cardiovascular-related mortality, and readmission risk in AHF patients. However, no significant connection was found between diabetes and survival outcomes with respect to the co-endpoint of death or readmission and the endpoint of in-hospital mortality. These findings underscore the necessity for implementing targeted diabetes management within AHF care protocols to enhance clinical outcomes, an essential consideration for future practice.