Conectar
by Yuzhong Feng, Jiazhen Cui, Xuan Huang, Yupeng Li, Haolong Dong, Xianghua Xiong, Gang Liu, Qingyang Wang, Huipeng Chen
Uricase-based drugs excel at treating refractory hyperuricemia and tumor lysis syndrome by directly degrading uric acid but are limited by immunogenicity. Here, we engineered RAW264.7 macrophages with ectopic co-expression of Aspergillus flavus uricase and murine urate anion transporter 1 (URAT1), forming a “transport-degradation” system: URAT1 actively transports uric acid into cells for intracellular degradation. Recombinant lentiviral vectors carrying target genes were transfected into RAW264.7 cells, followed by puromycin screening. In vitro assays showed that the engineered macrophages nearly completely degraded uric acid (from 556.0 ± 37.0 μmol/L to 0.7 ± 0.6 μmol/L) at 72 h. URAT1 inhibition with benzbromarone abolished uric acid degradation in URAT1-expressing cells. In both acute dietary-induced and chronic genetic hyperuricemic mouse models, RAW-afUri-URAT1 exerted robust and sustained uric acid-lowering activity, maintaining serum uric acid at 77.14 ± 37.48 μmol/L on day 16 in yeast extract gavaged mice and normalizing serum uric acid to 76.2 ± 15.9 μmol/L in liver uricase conditional knockout mice, both significantly superior to the rebound levels observed in mice treated with Rasburicase (143.19 ± 38.21 μmol/L and 142.4 ± 17.4 μmol/L, respectively; Pby Weifeng Wang, Xianli Meng, Yan Zhao, Wei Gong, Xiaochen Jiang, Wenjuan Cao, Xueling Qiu, Chenxi Sun, Fan Sun, Yuchen Wang, Lu Tang
BackgroundTo alleviate pain in burn patients during dressing changes, it is necessary to identify an effective analgesic method. Conventional opioid analgesics have many limitations. Nitrous oxide is a fast-acting, safe and reversible inhaled analgesic gas. This systematic review will evaluate the effectiveness and safety of nitrous oxide in the treatment of pain during dressing changes in burn patients.
MethodThe protocol was developed according to the PRISMA-P checklist and registered on PROSPERO (CRD42024550197). A systematic search will be performed in the following databases: PubMed, EMBASE, Web of Science, Cochrane Library to identify clinical trials comparing nitrous oxide inhalation with standard care in pain management during dressing changes in burn wounds. The search of all databases will be conducted on October 15, 2025.Our search scope will include studies published between each database creation and search date.Two researchers will independently screen studies, extract data, and evaluate study quality using the Risk of Bias2 tool. Primary outcomes will include pain, anxiety, side effects, among others.R statistical software (version 4.3.1) and R studio will be used to perform meta-analyses.Effect size will be expressed by 95% confidence interval (Cl) of weighted mean difference (MD) and risk ratio (RR). Subgroup analyses and sensitivity analyses will be performed to explore sources of heterogeneity and assess the robustness of the results.Publication bias will be assessed using funnel plot and Egger test. We will use the Grading of Recommendation, Evaluation, Development and Evaluation (GRADE) to assess the quality of the evidence.
DiscussionOperative pain has always been a difficult problem for burn patients. This study will evaluate the analgesic effect of nitrous oxide on dressing change in burn patients through comprehensive search and rigorous methods, and provide evidence support for clinical decision-making.
by Deye Ge, Liyan Wu, Jingrong Yang, Jingxian Sun, Jinying Wang, Jingxin Wang, Huihui Song, Ran Wei, Zecheng Xu, Binbin Zhao, Rongfei Sun, Yifei Wang
The U.S. Food and Drug Administration (FDA) approved intravenous edaravone for the treatment of amyotrophic lateral sclerosis (ALS) in 2017, followed by the approval of the oral formulation in 2022. This study aims to utilize the FDA#39;s Adverse Event Reporting System (FAERS) to investigate the spectrum and timing of adverse events (AEs) associated with edaravone administration, employing repeatability analysis, the Reporting Odds Ratio (ROR) approach, Weibull distribution, and stratification methods. The investigation focuses on data collected from the first quarter of 2017 through the fourth quarter of 2024, aiming to identify adverse event signals and their temporal patterns related to both intravenous and oral edaravone administration. In total, 3,262 records of edaravone-related adverse reactions were identified; among these, 1,534 incidents were associated with intravenous administration, while 453 incidents pertained to oral administration. The analysis revealed distinct adverse reaction profiles for the two routes of administration. Notably, the spectrum of adverse reactions resulting from oral administration predominantly involved the respiratory system, digestive system, and skin damage. In contrast, intravenous administration was more frequently linked to complications associated with invasive procedures and local tissue damage. Furthermore, the timing of adverse reactions exhibited significant variability between the two routes. Weibull distribution analysis indicated that the median onset time for adverse reactions following intravenous administration was 35 days, whereas for oral administration, it was 27 days. Both analytical approaches identified early failure signals, suggesting that the risk of adverse events diminishes over time.by Zonghan Lei, Yaoqi Hou, Xiangqin Song
Long-term motor training is thought to reshape brain organization, yet how golf expertise influences large-scale brain networks remains unclear. Using T1-weighted MRI and an individualized structural covariance network (SCN) approach, we compared 20 expert golfers, 20 novice golfers, and 20 non-golfer controls. Experts showed higher global clustering coefficient and local efficiency than novices, indicating enhanced modular processing. At the nodal level, experts exhibited increased clustering in regions supporting visual–sensorimotor integration (e.g., right supramarginal gyrus, Heschl’s gyrus, and left middle temporal pole), alongside reduced global efficiency in the left calcarine cortex and altered path length in the right cerebellum. Importantly, the clustering coefficient mediated the association between training duration and stroke accuracy. These cross-sectional findings suggest that extensive golf training is linked to a brain network reconfiguration that favors local specialization over global integration—potentially supporting the refined sensorimotor control required in elite performance. This study advances understanding of experience-dependent neuroplasticity by integrating individualized network analysis with behavioral outcomes in motor expertise.by Simon Söderholm, Martin Ulander, Vanessa William Toma, Sara Kaufmann, Xiangyu Qiao, Daniel Berglind, Susanna Calling, Bledar Daka, Ludger Grote, Mats Martinell, Frida Bergman, Pontus Henriksson, Carl-Johan Östgren, Wen Zhong, Claudio Cantù, Fredrik Iredahl
Coffee is the most common drink in the world, second only to water. This makes caffeine, the ingredient of coffee known for its wakefulness-promoting effects, one of the most used psychoactive substances. The psychoactive property of caffeine is well-characterized, and entails its interaction with the adenosine receptors, involved in sleep regulation. While studies have shown a deleterious immediate effect of caffeine on sleep, less is known about the effects of chronic caffeine exposure. In the present cross-sectional study, we investigated this relationship across a large cohort of 30,154 individuals participating in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), which allowed us to compare habitual coffee intake with sleep habits, subjective estimate of daytime sleepiness, and underlying genetic variants. According to our analyses, different degrees of coffee consumption, confirmed by statistical association with previously reported genetic variants, showed very low association with estimated patterns of sleep habits or perceived daytime sleepiness. These results indicate that coffee may be less impactful on sleep habits than previously thought, or that other mechanisms, such as the adaptive capabilities of the adenosine system in adult coffee users, may dampen its psychoactive potency.by Jingwen Ji, Xiangyuan Wu
Heavy metal pollution in coastal agricultural soils poses significant threats to food security, human health, and marine ecosystems. Effective prevention and control require systematic analysis of their spatial distribution and sources. This study integrated geostatistics, principal component analysis (PCA), positive matrix factorization (PMF), and finite mixture modeling (FMM) to comprehensively analyze the spatial variability and sources of five heavy metals (Cr, Pb, Cd, Hg, As) across 877 sampling sites in the coastal area of eastern Zhejiang. The results indicate that overall soil quality is good, though enrichment occurs at some sites due to anthropogenic activities. Pollution displays a spatial pattern of lower levels in the south and higher levels in the north. Pb is widely distributed, while Cd, Hg, and As are concentrated in agricultural plain areas. PMF-based source apportionment revealed that mobile sources (traffic) contributed the most (52.5%), followed by industrial sources (30.4%) and agricultural sources (17.1%). The consistency of multi-model results validated the reliability of source identification. By implementing precise management strategies based on pollution source contributions, it is expected to effectively curb the further deterioration of heavy metal pollution in agricultural soils in Zhejiang Province, gradually improve soil environmental quality, and ensure the safety of agricultural products and the sustainable development of agriculture.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 Qiaoling Li, Jing Zhang, Shasha Meng, Fengxiang Tian, Qinqin Mei, Hui Wang, Hong Qi
BackgroundSelf-regulated fatigue is often assessed in studies of chronic diseases. Research is needed on the self-regulation of fatigue and physical activity in lung cancer patients undergoing treatment, and the impact of these factors on this population.
ObjectiveThe goal of this study is to investigate the current status, influencing factors, and correlation between self-regulatory fatigue and physical activity in lung cancer patients undergoing comprehensive treatment.
MethodsWe used a convenience sampling method to enroll 188 lung cancer patients admitted to two tertiary hospitals in Chengdu from October 2024 to April 2025. Data were collected using a general information questionnaire and two scales: the Self-Regulatory Fatigue Scale (SRF-S) and The International Physical Activity Questionnaire-long form (IPAQ-L).
ResultsThe mean self-regulatory fatigue score was 42.19 ± 9.06. The total metabolic equivalent (MET) of physical activity was 544.00 (0.00, 1386.00) MET-min/week, with leisure-time activity accounting for 429.00 (0.00, 1188.00) MET-min/week (data presented as median and interquartile range). Significant negative correlations were observed between Self-Regulatory Fatigue total scores and energy expenditure from housework, leisure activities, as well as total physical activity expenditure. Furthermore, self-regulatory fatigue was negatively correlated with both moderate-intensity and low-intensity physical activity, but positively correlated with high-intensity physical activity (P P R² = 0.306).
ConclusionEngaging in appropriate leisure and household activities at moderate-to-low intensity may help alleviate the severity of self-regulatory fatigue in lung cancer patients undergoing comprehensive treatment. Healthcare providers should encourage appropriate activity to reduce the psychological burden and conserve self-regulatory resources.
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 Zihang Zhao, Xiang Zhang, Xi Hou, Zihan Liu, Zhiyong Hou, Lianxin Song, Ruipeng Zhang
Percutaneous Bunnell repair and open modified Kessler repair remain debated options for acute Achilles tendon rupture (AATR). We retrospectively compared a minimally invasive percutaneous Bunnell technique (Group A) with an open modified Kessler repair (Group B) within a standardized early functional rehabilitation (EFR) protocol at a single center. Fifty-five adults with closed AATR treated between January 2021 and December 2022 were analyzed (Group A, n = 25; Group B, n = 30). Between-group comparisons used Welch t tests for continuous variables and χ² or Fisher exact tests for categorical variables; American Orthopaedic Foot & Ankle Society (AOFAS) and Achilles Tendon Total Rupture Score (ATRS) were assessed at 12 and 24 weeks, with Holm adjustment applied within each scale. Compared with Group B, Group A had shorter operative time (56.6 ± 15.1 vs 68.2 ± 23.2 minutes; mean difference −11.6; 95% CI −22.05 to −1.15; P = 0.030), less intraoperative blood loss (28.4 ± 8.4 vs 74.7 ± 19.4 mL; −46.3; 95% CI −54.22 to −38.38; Pby Xianxiang Lu, Yangrui Duan
Resilience is a crucial ability of an economy to withstand sudden events and uncertain shocks. Using the entropy method, this study measures the economic resilience of 281 Chinese cities (prefecture-level and above) from 2017 to 2022, and empirically examines the impact of COVID-19 on this resilience, as well as its transmission channels. The results show that COVID-19 adversely affected overall urban economic resilience, with contrasting effects across its sub-dimensions: an insignificant negative impact on shock resistance, a significant negative impact on adaptive recovery, and an insignificant positive impact on innovative transformation. Transmission channels analysis reveals COVID-19 impaired urban economic resilience through the channels of employment structure, consumption, investment, and unrelated diversification, with consumption identified as the predominant one. Heterogeneity analysis reveals that the economic resilience of cities in both the high and low manufacturing specialization groups was more adversely affected by COVID-19 than that of cities in the medium group. Regarding services specialization, the economic resilience of cities with a medium degree of services specialization were more negatively affected by COVID-19 than that of cities with low services specialization. Furthermore, the economic resilience of cities with a higher degree of related diversification was less negatively affected by COVID-19. This study provides a replicable analytical framework and empirical evidence for enhancing urban economic resilience in China and other countries in post-pandemic era.by Bing Wu, Pengli Wei, Jiaxiang Deng, Yuanyuan Rui
BackgroundThe atherogenic index of plasma (AIP) is a recognized marker of atherosclerosis and cardiovascular disease (CVD). However, the association between AIP and the risk of acute kidney injury (AKI) in critically ill patients with sepsis has not yet been investigated.
MethodsThe data used in this study were derived from the Medical Information Mart for Intensive Care (MIMIC-IV) database. The clinical outcome was the occurrence of AKI. Logistic regression was used to assess the association between AIP and the risk of AKI in sepsis patients. Restricted cubic spline (RCS) analysis was applied to explore potential non-linear relationships. Threshold analysis confirmed a turning point at this value. Subgroup analyses evaluated the consistency of the association across different strata. Mediation analysis was performed to explore potential intermediate variables.
ResultsAmong 1,874 sepsis patients, higher AIP levels were associated with increased AKI incidence. Logistic regression showed a significant association between AIP and AKI in unadjusted and partially adjusted models, but the association was no longer significant after full adjustment. RCS analysis revealed a nonlinear relationship with a peak AKI risk at AIP = 1.333. Threshold analysis confirmed a turning point at this value. Subgroup analyses showed consistent associations, while nonlinear effects were more evident in specific groups. Mediation analysis suggested that SOFA score, creatinine, WBC count, and respiratory rate partially mediated the AIP-AKI relationship.
ConclusionAIP was nonlinearly associated with AKI in sepsis, with a clear threshold effect. This relationship was partially mediated by SOFA score, creatinine, WBC, and respiratory rate. AIP may serve as a useful marker for AKI risk assessment.
by Xiaoliang Wan, Feiyao Deng, Xue Bai, Chenxi Xiang, Chuan Xu, Linxiao Qiu
Dysregulated serum chloride levels are prevalent in critically ill patients. However, their clinical impact remains unclear. This first systematic review and meta-analysis quantified the prevalence of hypochloremia and hyperchloremia, and their associations with mortality and acute kidney injury (AKI) in critically ill populations. We searched PubMed, Embase, Web of Science, and the Cochrane Library for studies reporting hyperchloremia prevalence or outcomes in adult ICU patients until August 2025. Statistical analyses were conducted using Stata v16.0, and study quality was assessed using the Newcastle-Ottawa Scale. 34 studies (n = 175,021 patients) were included. The aggregated prevalence of hyperchloremia was 34% (95% CI [26%−43%]) and hypochloremia was 14% (95% CI [1%−28%]). Meta-analysis demonstrated that both hyperchloremia and hypochloremia were significantly associated with increased mortality, conferring a 28% (OR = 1.28, 95% CI [1.08–1.52]) and 55% (OR = 1.55%, 95% CI [1.33–1.81]) elevated risk for mortality, respectively. Crucially, a dose-response analysis revealed a non-linear relationship between serum chloride levels and mortality, confirming that the risk is independently elevated at both extremes. Furthermore, hyperchloremia was linked to an increased risk of AKI (OR = 1.40, 95% CI [1.07–1.85]). These findings establish dysregulated serum chloride as a common and clinically significant biomarker, underscoring the necessity of monitoring and managing both high and low chloride levels in critically ill patients. Future large-scale studies are warranted to validate these results and elucidate the mechanistic pathways linking chloride dysregulation to such adverse outcomes.by Yunhao Jiang, Gang Liu, Yulun Du, Siteng Cai, Zhichao Si, Jing He, Xiangbing Zhou
Urban large-scale complexes, such as shopping malls, pose significant challenges for fire safety management due to their intricate spatial layouts, high population density, and diverse occupancy characteristics. Efficient fire evacuation strategies are critical for minimizing casualties and economic losses; however, existing approaches often overlook the dynamic interplay between fire propagation and human behavior, resulting in suboptimal safety assessments. This study proposes an integrated simulation framework to optimize evacuation strategies by coupling fire dynamics with pedestrian flow modeling, aiming to enhance both evacuation efficiency and personnel safety. The methodology comprises three key steps: (1) Fire scenario simulation: A Building Information Modeling (BIM)-based digital platform is constructed to simulate fire propagation. Critical fire parameters (e.g., heat release rate, combustion model) are calibrated to quantify temporal variations in smoke temperature, CO concentration, and visibility across different zones. (2) Evacuation dynamics modeling: A pedestrian evacuation model is developed by integrating demographic factors (age structure, movement speed, population density) and fire-induced regional risks, enabling realistic simulation of crowd movement under fire conditions. (3) Safety performance evaluation and strategy optimization: Safety margins at staircases are assessed by comparing Required Safe Egress Time (RSET) and Available Safe Egress Time (ASET), followed by a safety grading system to identify high-risk bottlenecks. Evacuation strategies are then optimized to mitigate these risks. A case study was conducted on a shopping mall in Chengdu to validate the framework. Simulation results indicate an initial evacuation time of 260.4 seconds. Safety performance analysis revealed critical risks at staircases A and C (1st floor) and D (2nd floor) due to insufficient safety margins. After strategy optimization, the total evacuation time was reduced to 245.5 seconds, with safety margins at the three high-risk staircases increased by 130.8 s, 115.2 s, and 72 s, respectively, fully meeting safety requirements. The overall evacuation efficiency was significantly improved. This study demonstrates the effectiveness of the proposed framework in quantifying fire risks and optimizing evacuation strategies for large-scale complexes. The integrated simulation approach provides a scientific basis for evidence-based safety management and evacuation planning, offering valuable insights for urban fire safety engineering and emergency response optimization.by Wenxiang He, Jianwu Chen
Sirtuin 4 (SIRT4) plays a critical role in regulating oxidative stress, apoptosis, and mitochondrial dysfunction in diabetic nephropathy (DN). This study employed a multi-step in silico strategy to identify novel SIRT4 modulators with potential therapeutic relevance for DN. A ligand-based pharmacophore model was developed using UBCS182, followed by virtual screening of 3,285 compounds from major chemical libraries. Molecular docking revealed strong binding affinities (−9.46 to −8.41 kcal/mol), with CSC057320968, PubChem-162316407, and ChemDiv-V013-1548 emerging as top candidates. ADMET analysis confirmed their favorable pharmacokinetic and toxicity profiles. Subsequent 200 ns molecular dynamics simulations demonstrated the stability of protein–ligand complexes, with CSC057320968 exhibiting the most stable interaction profile based on RMSD, RMSF, Rg, and contact frequency analyses. Principal component analysis and free energy landscapes indicated conformational rigidity and energetic favorability for CSC057320968. Density Functional Theory (DFT) analysis further validated its reactivity and chemical softness, supporting its potential as a lead scaffold. This integrated computational pipeline provides novel insights into SIRT4 modulation and offers a rational framework for targeting mitochondrial dysfunction in DN.by Min Lu, Zixuan Bu, Nana Xiang, Juebo Yu
COVID-19 Vaccinations are associated with higher allergic reactions risk among adults. However, evidence on whether no vaccinated with COVID-19 vaccine is associated with fewer incidence among individuals with atopic diseases remains limited. This study is to investigate whether COVID-19 Vaccination is associated with increased risk of adult atopic diseases. A cross-sectional survey was conducted using data from the 2021 US National Health Interview Survey (NHIS) that included 29201 respondents aged 18 years or older adults. Multivariable logistic regression was conducted to estimate the association of COVID-19 vaccination and atopic disease. Crude and adjusted odds ratios (aORs) and 95% CIs were estimated. Analysis of the data was performed from October 01, 2023, to January 22, 2024. Of 29201 respondents (mean [SD] age, 52.6 [18.4] years; 13240 [45.3%] male), the US prevalence was 49.6% (unweighted, 95% CI, 49.1%−50.2%) from all years of the2021 NHIS for self-reported hay fever, 13.7% (unweighted,95% CI, 13.3%− 14.1%) for asthma, 10.9% (unweighted, 95% CI,10.1%−11.3%) for skin allergy, 10.0% (unweighted,95% CI, 9.7%−10.4%) for food allergy, and 45.1% (unweighted,95% CI, 45.6%−45.7%) for no COVID-19 vaccination, 6.4% (95% CI, 6.1%−6.9%) for one COVID-19 vaccination, 43.1% (unweighted, 95% CI, 42.6%−43.7%) for two COVID-19 vaccinations, 5.3% (unweighted, 95% CI, 5.1%−5.6%) for more than 2 COVID-19 vaccinations. In multivariable analysis across the 2021 NHIS, COVID-19 vaccinations does not increase the risk of skin allergy(aOR, 1.03;95%CI, 0.86–1.28; P = 0.135), asthma (aOR, 1.05;95%CI,0.98–1.13; P = 0.164), and food allergy (aOR, 1.03;95%CI, 0.95–1.12; P = 0.437) in adults, compared with adults without COVID-19 vaccination; whereas, in patients with COVID-19 vaccination had significantly higher odds of hay fever (aOR, 1.21;95% CI, 1.15–1.27;P
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