Conectar
by Ying Fei, Ming-Yi Gao, Nan Qiao, Jia Hu, Ling He, Jiao-Li Zhou, Ning-Ning Zheng, Ting-Ting Liu
BackgroundThe effect of fecal microbiota transplantation (FMT) in treating irritable bowel syndrome (IBS) may be attributed to the modulation of CD8 + T cells. This study aims to identify FMT-mediated key genes to explore the underlying mechanism.
MethodsTranscriptomic datasets GSE138297 (colonic biopsies from 8 IBS patients pre- and post-FMT) and GSE134649 (single-cell data from 3 healthy colon tissues) were obtained from GEO during December 2023–December 2024. Key genes were identified by intersecting differentially expressed genes (DEGs) and the most relevant co-expression module derived from weighted correlation network analysis. Functional enrichment, gene set enrichment analysis, immune infiltration profiling via TIMER 2.0, single-cell annotation using PanglaoDB and Seurat, and drug–gene interaction screening from DrugBank were conducted to decipher the regulatory mechanisms.
ResultsTen key genes were identified through integration of DEGs and the MEgreen module. Functional analyses revealed significant involvement in the positive regulation of CD8 + T cells activation. Immune infiltration assessment demonstrated a marked increase in CD8 + T cells abundance post-FMT. Single-cell data indicated predominant expression of LILRB1, P2RY13, CLEC10A, and CLEC12A in dendritic cells, and LILRB1, PIPOX, and CLEC11A were annotated within CD8 + T cells clusters in healthy colonic tissue. Nine (database-derived and speculative) drugs targeting seven key genes were identified, most implicated in the management of IBS symptoms or immunomodulation.
ConclusionAn association between key gene regulation and CD8 + T cell-related immunoregulation is correlated with the therapeutic effect of FMT in IBS.
by Wen Lin, Qiong-zhi Shi, Xiang-ru Liao, Yuan Zeng, Xiang-yang Xie, Gang-jian Ji, Yin-ke Li
Burn wound infections are frequently complicated by biofilm-forming and multidrug-resistant pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), posing major therapeutic challenges. Antimicrobial peptides (AMPs) such as PL-5 (peceleganan) exhibit broad-spectrum activity but are limited by instability, poor biofilm penetration, and reduced efficacy in complex wound environments. Here, a red-light-responsive, porphyrin-phospholipid (PoP)-containing cationic liposomal system for PL-5, aiming to enhance its antibacterial and antibiofilm performance was developed. Optimized liposomes achieved high encapsulation efficiency (~73%), uniform nanoscale size (~50 nm), narrow polydispersity, and positive surface charge. They demonstrated good storage stability and controlled peptide release under red-light irradiation (635 nm). In vitro, red-light activation significantly enhanced antimicrobial activity against MRSA and methicillin-susceptible S. aureus (MSSA), reducing minimum inhibitory concentration (MIC) values fourfold and accelerating bactericidal kinetics compared with free PL-5 and non-irradiated liposomes. Additionally, red-light-activated liposomes markedly inhibited biofilm formation. These results indicate that light-responsive liposomal delivery enables spatiotemporally controlled release of PL-5, significantly potentiating its antibacterial and antibiofilm efficacy. This approach offers a promising localized treatment strategy for biofilm-associated burn wound infections and a foundation for future translational studies.by Qian Li, Yilun Huang, Samuel Yeung-Shan Wong, Winnie W. S. Mak, Xue Yang
Background and objectiveA well-established link exists between depression and Internet gaming disorder (IGD) at the individual level, while it remains unexplored within the family system. This study aims to investigate the interdependent relationship between parent and adolescent depression and IGD, and to identify the potential mechanisms.
MethodsA cross-sectional dyadic study was conducted with adolescents and their parents (primary caregiver) in Hong Kong. Adolescents completed anonymous surveys in classrooms, and parents completed online surveys via WhatsApp or phone interviews. The Actor-Partner Interdependence Model (APIM) and Actor-Partner Interdependence Mediation Model (APIMeM) were utilized to test the interdependence and mediators between depression and IGD in parent-child dyads, respectively.
ResultsA total of 1,277 parent-child dyads were included. Depressive symptoms in parents (β = 0.072) and adolescents (β = 0.273, both p Conclusions
Adolescent depressive symptoms were positively associated with their own and parental IGD symptoms, which were mediated by adolescent-reported family relationships and adolescent gaming time. The influence of adolescents’ mental health problems on parents’ problematic behaviors within the family system should not be overlooked.
by Zhiheng Qian, Ni Jiang
BackgroundDelayed gastric emptying and gastroesophageal reflux represent critical yet frequently underrecognized complications in hospitalized patients, particularly in the context of polypharmacy. While multiple medication classes have been implicated in disrupting gastrointestinal motility, the comprehensive risk spectrum of individual drugs remains poorly characterized. This study aimed to conduct a comprehensive disproportionality analysis to identify drugs associated with delayed gastric emptying and reflux using large-scale pharmacovigilance data.
MethodsWe analyzed adverse event reports from the FDA Adverse Event Reporting System (FAERS; 2004–2025; n > 58 million) and validated findings against the Canada Vigilance Adverse Reaction Online Database (CVARD). Disproportionality analysis was performed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN). Weibull time-to-onset analysis was conducted to characterize temporal patterns of adverse event onset.
ResultsAmong the top 50 drugs screened, 20 demonstrated positive signals across all three algorithms. Glucagon-like peptide-1 (GLP-1) receptor agonists exhibited the strongest associations with gastric motility disorders, with semaglutide showing the highest ROR for impaired gastric emptying (ROR: 80.27; 95% CI: 76.39–84.34), validated in CVARD (ROR: 54.17). Insulin formulations, particularly insulin degludec (ROR: 18.90), bisphosphonates, angiotensin receptor blockers, and trofinetide also demonstrated significant signals. Weibull analysis revealed divergent temporal patterns, ranging from early-onset (trofinetide: median 6.6 days) to late-onset (immunoglobulin G: median 535.1 days).
ConclusionThis study identifies a broad spectrum of drug-associated gastric motility disorders with distinct temporal profiles. These findings provide evidence-based priorities for enhanced pharmacovigilance and inform clinical decision-making to mitigate this preventable cause of morbidity.
by Qingyuan Li, Yousong Yue
ObjectiveTo assess long-term trends in height, weight and body mass index (BMI) among children and adolescents from 2005 to 2020 in Macao Special Administrative Region (SAR), China.
MethodsHeight, weight and BMI data for Macao children and adolescents aged 6–18 years were obtained from the Physical Fitness Reports of Macao SAR Residents in 2005, 2010, 2015, and 2020. Sex-specific two-way analysis of variance was used to estimate the differences in means. The Bonferroni post hoc test was used for multiple comparisons.
ResultsDuring the entire period, the average height, weight and BMI increased by 2.1 cm (95% confidence interval (CI): 1.6 to 2.6 cm), 4.0 kg (95% CI: 3.2 to 4.8 kg), and 1.1 kg/m2 (95% CI: 0.8 to 1.3 kg/m2) for boys and 2.4 cm (95% CI: 1.9 to 2.9 cm), 2.6 kg (95% CI: 1.9 to 3.3 kg), and 0.5 kg/m2 (95% CI: 0.3 to 0.8 kg/m2) for girls, respectively (p Conclusion
There were positive long-term trends in growth among Macao children and adolescents since 2005. Sex differences in changes of weight and BMI over the past five years may be related to the pandemic, and efforts are needed by governments and public health departments.
by Hongzhen Yin, Tong Wang, Changshun Zhong, Yingya Cao, Xiaogan Jiang, Qiancheng Xu, Weihua Lu
Airway foreign-body aspiration in adults is uncommon but can be life-threatening.Flexible bronchoscopy is the standard first-line therapy,but critically ill patients may need extracorporeal life support.This study aims to characterize the diagnosis,management,and outcomes of adult airway foreign-body cases treated at a single center over nearly 12 years to inform a standardized clinical pathway.A single-center retrospective observational study of consecutive patients aged ≥14 years with confirmed airway foreign body who were treated at a tertiary hospital in China were conducted.Medical records of consecutive adolescent and adult patients diagnosed with airway foreign-body aspiration and admitted to the hospital from 01/01/ 2014–30/11/2025 were reviewed.Data included demographics,imaging,extraction method, respiratory support and so on.Descriptive statistics were reported as medians with interquartile ranges or counts and percentages.A total of 41 patients were included,with a median age of 59.5 years(interquartile ranges 51–72) and 65.85% male.Flexible bronchoscopy was attempted as the primary intervention in 38 patients(92.68%) and succeeded in 81.58%(31/38) to remove airway foreign body.Most patients(78.05%) required only nasal cannula oxygen,while nine patients(21.95%) needed advanced support including mechanical ventilation (14.63%),high-flow oxygen(4.88%),and extracorporeal life support (2.44%).At discharge,most survivors had a good neurological outcome,with 36 patients(87.80%) having a Cerebral Performance Categories score of 1.The 28-day survival rate was 92.68%.These findings show that flexible bronchoscopy is an effective first-line therapy,and rigid bronchoscopy or surgery is useful when flexible bronchoscopy fails.In unstable cases,timely extracorporeal life support can bridge to definitive removal.These results support a tiered,multidisciplinary approach incorporating early chest computed tomography,flexible bronchoscopy,and escalation to advanced airway or extracorporeal support.by Yanan Zhu, Qian Wang, Huiying Jia, Gaiyun Zhao, Yunpeng Lü, Xinhong Zhang, Haijing Dong
This randomized controlled trial is aimed at evaluating whether external fixation of the urinary catheter to the body surface represents a low-value nursing intervention for patients undergoing transurethral resection of the prostate (TURP). A total of 208 patients who received indwelling urinary catheters after TURP in a tertiary hospital in Qingdao, China between June 2024 and May 2025 were randomly assigned to one of two groups: a nonexternal fixation group (n = 103) and an external body surface fixation group (n = 105). A between-group comparison of outcomes included postoperative hematuria, incidence of catheter-associated urinary tract infection (CAUTI), unplanned catheter removal, occurrence of urinary catheter-related meatal pressure injury (UCR-MPI), and associated economic costs. No significant differences were observed between the two groups in terms of postoperative hematuria or CAUTI incidence (P > 0.05). Unplanned catheter removal did not occur in either group. However, UCR-MPI occurred significantly more frequently in the external fixation group (9 patients) than it did in the nonexternal fixation group (1 patient) (Pby Lu Zhang, Si Wang, Jie Lei, Lingrui Zeng, Ailin Lu, Yongqing Wu, Yuan Shi, Jing Yang, Mengrui Yuan, Hongyi Liu
BackgroundDiabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) and is closely linked to immune and inflammatory dysregulation. Multi-component pharmacological interventions have been explored as complementary approaches for metabolic and immune modulation; however, their effects on DPN and related mechanisms remain incompletely understood.
MethodsA rat model of T2DM-associated peripheral neuropathy was established, and a multi-component pharmacological intervention (MPCI) was administered for 8 weeks. Peripheral nerve dysfunction was evaluated by motor and sensory nerve conduction velocities (MNCV and SNCV), behavioral outcomes, and histological/ultrastructural assessments. In parallel, spleen tissues were collected for transcriptomic profiling. RNA sequencing was performed to identify differentially expressed genes and immune-related pathways, and representative molecules involved in inflammatory regulation were further validated using western blotting and quantitative real-time PCR in sciatic nerve tissue.
ResultsMPCI administration significantly ameliorated peripheral nerve dysfunction in T2DM rats, as evidenced by improved nerve conduction velocities and pathological features. Transcriptomic analysis of spleen tissue revealed that MPCI was associated with broad remodeling of diabetes-related immune and inflammatory gene programs. In parallel, sciatic nerve analyses showed attenuation of NF-κB/c-Jun–associated inflammatory signaling and modulation of inhibitory regulators at both the protein and mRNA levels.
ConclusionThese findings indicate that MPCI improves T2DM-associated DPN and is associated with splenic immune remodeling and attenuation of peripheral nerve inflammatory signaling, providing exploratory evidence for associations between splenic immune transcriptomic remodeling and peripheral nerve inflammatory signaling.
by Qian He, Xu Huang
BackgroundSepsis-induced immunosuppression is a key factor contributing to high mortality rates. However, suitable biomarkers for routine clinical monitoring of immune function are currently lacking. Serum cholinesterase levels are markedly diminished in sepsis and are associated with unfavorable prognoses, its role in the immunosuppression pathology and the mechanisms involved remain inadequately understood.
MethodsWe conducted a translational study integrating clinical research, bioinformatics analysis and animal experiments. Initially, within a single-center clinical cohort, we investigated the correlation between serum cholinesterase levels and lymphocyte subsets in patients suffering from sepsis, subsequently evaluating its association with disease severity (APACHE-II and SOFA scores) and clinical outcomes. Subsequently, by integrating sepsis transcriptome data with cholinergic anti-inflammatory pathways and immune-related gene sets, we identified the hub gene RORA and validated it across multiple dimensions using public databases. Finally, in the CLP sepsis mouse model, we measured cholinesterase activity and specifically quantified RORA mRNA expression in the spleen. We then analyzed the correlation between these measurements and changes in key immune cell counts.
ResultsClinical data revealed significantly reduced serum cholinesterase activity in sepsis patients. Decreased cholinesterase levels positively correlated with elevated disease severity scores (APAChE-II, SOFA) and reduced counts of CD4 ⁺ T cells, CD8 ⁺ T cells, and NK cells. Bioinformatics analysis identified RORA as a hub gene linking sepsis, cholinesterase, and immune responses. Across eight independent GEO datasets, RORA expression exhibited a consistent downregulation trend in sepsis with high diagnostic value. Analysis of immune cell infiltration revealed significant positive correlations between RORA and counts of CD4 ⁺ T, CD8 ⁺ T, and NK cells in sepsis. In the CLP mouse model, reductions in spleen CD3 ⁺ T, CD4 ⁺ T, and CD8 ⁺ T cell counts coincided with notable decreases in serum cholinesterase and spleen RORA mRNA levels. Both serum cholinesterase concentration and spleen RORA mRNA expression exhibited positive correlations with CD4 ⁺ T and CD8 ⁺ T cell counts.
ConclusionThis study establishes serum cholinesterase as a valuable clinical biomarker for assessing sepsis diagnosis, disease severity, and immunosuppression. For the first time, through multiomics integration and experimental validation, RORA has been identified as the key molecular bridge linking the cholinesterase activity and immunosuppression in sepsis. This not only provides a new direction for understanding immune dysregulation in sepsis but also lays a theoretical foundation for the future development of RORA-targeted immunomodulation and treatment strategies for sepsis.
by Shuhong Zheng, Renxiu Bian, Haixin Song, Zhiping Liao, Ting Gao, Min Yan, Heqing Huang, Zuodong Lou, Fangchao Wu, Jianhua Li
BackgroundLow-intensity focused ultrasound (LIFU) is a non-invasive neuromodulation technique with high spatial precision and the ability to reach deeper brain regions, offering potential advantages for post-stroke rehabilitation. Repetitive transcranial magnetic stimulation (rTMS) is a widely adopted non-invasive brain stimulation technique that modulates cortical excitability to promote neuroplasticity. However, direct head-to-head comparisons between these two modalities for post-stroke motor recovery remain limited.
ObjectiveTo perform a secondary head-to-head comparison of LIFU and repetitive transcranial magnetic stimulation (rTMS) for motor recovery after stroke, based on a prospectively registered randomized controlled trial.
MethodsThis secondary analysis included patients with subacute stroke who received two weeks of standard rehabilitation combined with either LIFU (n = 25) or rTMS (n = 25) targeting the ipsilesional primary motor cortex. LIFU parameters: 0.5 MHz, spatial-peak pulse-average intensity (ISPPA) 10.2 W/cm² (free-field), pulse duration 0.2 ms, duty cycle 20%, 20 minutes per session, five days per week for two weeks (10 sessions total). rTMS parameters: 10 Hz, 80% resting motor threshold, 1,000 pulses per session (20 trains of 5 seconds), 20 minutes per session, five days per week for two weeks (10 sessions total). Motor outcomes were assessed using the Fugl–Meyer Assessment (FMA; upper and lower extremities), Modified Barthel Index (MBI), and Brunnstrom stages. Resting-state functional near-infrared spectroscopy (fNIRS) was used to evaluate cortical activity and functional connectivity before and after the intervention. Primary analyses were conducted in the intention-to-treat (ITT) population (n = 50), with completer analyses (n = 43) performed as sensitivity analyses.
ResultsBoth groups showed significant within-group improvements in FMA and MBI after the intervention (all p 0.05), and completer analyses yielded consistent between-group conclusions. In contrast, change-from-baseline analyses demonstrated greater improvements in FMA scores in the LIFU group compared with the rTMS group (ΔFMA upper limb: median 7 [IQR 3–10.5] vs. 2 [1–3], p = 0.001; lower limb: 3 [1–4.5] vs. 1 [0–1.5], p Conclusion
LIFU and rTMS were associated with comparable short-term motor outcomes in subacute stroke. Differences observed in change-from-baseline motor improvements and exploratory neuroimaging measures suggest potential divergence in recovery dynamics and cortical modulation, warranting further investigation in larger, longitudinal studies.
Trial registrationThis study was derived from a prospectively registered, three-arm randomized controlled trial in the Chinese Clinical Trial Registry (ChiCTR2500114687). The present manuscript reports a secondary head-to-head comparison between the two neuromodulation intervention arms.
by Fangqing Liu
BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that activates vagal afferents projecting to prefrontal–limbic circuits implicated in attention, memory, and emotion regulation. Preliminary studies suggest that taVNS may enhance cognitive performance; however, the evidence remains fragmented across domains and populations.
ObjectivesThis systematic review and meta-analysis aim to (1) quantify the overall effects of taVNS on cognitive functions, (2) examine its efficacy across clinical and non-clinical populations, and (3) identify moderators influencing variability in outcomes, including stimulation parameters, participant characteristics, and study design features.
MethodsFollowing PRISMA-P guidelines, this protocol will be prospectively registered with PROSPERO. Six databases (PubMed, EMBASE, PsycINFO, Web of Science, CENTRAL, and Scopus) and major trial registries will be systematically searched. Eligible studies include randomised controlled trials assessing validated cognitive outcomes following taVNS compared with sham or active controls. Effect sizes will be calculated as Hedges’ g and pooled using random-effects models. Heterogeneity will be evaluated with I² and τ statistics; moderator and meta-regression analyses will explore dose–response and population effects. Risk of bias will be assessed with RoB 2 for randomised trials and ROBINS-I for non-randomised studies, and the certainty of evidence will be rated using GRADE separately by study design.
Expected Results and ConclusionsThis review will provide the first quantitative meta-analytic synthesis of taVNS-induced cognitive modulation across executive, attentional, affective, and learning domains in both clinical and healthy populations, complementing recent narrative syntheses by offering pooled effect size estimates, formal heterogeneity assessment, and a GRADE-rated evidence hierarchy. By delineating domain-specific efficacy and optimal stimulation parameters, the findings aim to inform future clinical applications and the development of standardized neuromodulation protocols.
by Zhilan Huang, Tingyi Xie, Mingwen Tang, Zhuni Chen, Dan Jia, Anqi Su, Zhujin Jin, Tuliang Liang, Wei Xie
BackgroundPulmonary fibrosis is a severe chronic lung disease whose prevalence has been rising in recent years, representing one of the major respiratory health challenges globally in the 21st century. The burden of this disease on the elderly population is garnering growing attention, particularly as the global population ages. The Global Burden of Disease (GBD) study has provided valuable insights; however, systematic analyses focused on this condition remain limited. To date, few studies have specifically examined interstitial lung disease and pulmonary sarcoidosis among individuals aged 55 years and older. This study aims to conduct a comprehensive analysis of burden trends from 1990 to 2021 for those aged 55 and above and to project future trends up to 2035.
MethodsOur approach utilizes the estimation of four broad component measures: incidence, prevalence, death and Disability-Adjusted Life Years (DALYs), using data on ILD&PS from the Global Burden of Disease (GBD) 2021 database. Joinpoint regression models were applied to calculate the average annual percentage change (AAPC) in order to analyze temporal trends in disease burden and to identify years with significant trend shifts. Analyses were further stratified by age, sex, region, country, and Sociodemographic Index (SDI). Additionally, a Bayesian age-period-cohort (BAPC) model was used to project future disease burden trends.
ResultsBetween 1990 and 2021, significant increases were observed in incidence, DALYs, and death rates for ILD&PS (AAPC incidence = 1.09, 95% CI: 1.04 to 1.15; AAPC DALYs = 1.10, 95% CI: 0.97 to 1.23; AAPC death = 1.65, 95% CI: 1.47 to 1.83). In 2021, the total number of incident cases reached 284,887 (95% UI 248,300–328,800), with the highest incidence rates observed in Andean Latin America. Across age- and sex-specific analyses, global burden trends were similar, though males consistently exhibited higher rates than females. The oldest age group (95 + years) had the highest incidence and DALYs rates among all age strata. Furthermore, incidence rates increased most markedly in high-SDI regions, showing a strong positive correlation between SDI and incidence. Bayesian age–period–cohort (BAPC) analyses indicated that while prevalence rates are projected to decline slightly, incidence rates are expected to continue rising. Both males and females showed a dip then rise in prevalence trends, but the increase was more pronounced among females. In 2035, the highest number of incident cases is projected to occur in the 65–69 age group, whereas the highest incidence rate is predicted in the 95 + age group.
ConclusionsA concerning upward trend in incidence, DALYs, and deaths related to ILD&PS was observed in the global population aged 55 years and older, particularly among females. To our knowledge, this is the first study to comprehensively analyze the burden of ILD&PS in this age group from 1990 to 2021. Our findings on epidemiological trends and their variations across geography, SDI, age, and sex can inform policy-makers in designing targeted strategies to mitigate the anticipated rise in disease burden.
by Yang Tong, Huang Qianzhen, Tan Bo, Hu Bin, Zhang Min
BackgroundAdvancing the development of centers for disease control and prevention (CDCs) has become a priority within global public health governance. However, public health governance capacity varies significantly among CDCs across different countries and regions, grassroots CDCs face particular disadvantages. Establishing stable, efficient collaborative development mechanisms among CDCs across diverse regions to maximize overall effectiveness and ensure sustainable development represents a critical public health science issue.
ObjectiveThis study aims to provide scientific references and a theoretical foundation for the coordinated development of grassroots CDCs within the Chengdu–Chongqing Economic Circle (CCEC) and the construction of public health systems.
MethodsA questionnaire for collaborative development needs indicators in grassroots CDCs, comprising 4 primary needs and 13 secondary needs, was developed through literature review, the Delphi expert consultation method, and the Kano model. Analysis focused on questionnaires collected from eight grassroots CDCs within the CCEC. The importance of needs was ranked using the better–worse coefficient and satisfaction sensitivity analysis.
ResultsAnalysis of the 110 valid questionnaires showed that for the must-be attribute, satisfaction sensitivity ranked as follows: performance compensation (0.883)> talent exchange and scientific research and innovation cooperation (0.824)> public health emergency rescue mechanism (emergency material reserve and cross-regional material mobilization; 0.817)> cross-regional case monitoring, investigation, and tracking (0.775). Regarding the one-dimensional attribute, the satisfaction sensitivity ranking was joint risk assessment and emergency command (0.937)> business archive co-construction and sharing mechanism (emergency response plan, and technical scheme) (0.909)> regional co-construction and sharing between the university and the local area (0.832). For the attractive attribute, the satisfaction sensitivity ranking was regional monitoring and early-warning information management system (0.922)> community chronic disease prevention and service (0.804)> coordinated transfer and diversion diagnosis and treatment of patient with infectious diseases within the region (0.734). However, the collaborative release and interaction mechanism of social integrated media information, public health collaborative governance entities, and the construction of a cross-regional expert database constitute indifferent attributes.
ConclusionsThis study provides preliminary scientific evidence for the precise allocation of public health resources and the establishment of localized collaborative development mechanisms. Simultaneously, the research methodology and analytical framework offer new theoretical references for similar studies in other regions globally.
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 Qin Zhang, Yuhong Hu, Xiaoju Li
With the rapid development of information and communication technologies, modern fire rescue models are evolving towards informatization, proactivity, and spatialization. Existing fire simulation models primarily focus on the impact of individual building parameters, lacking a systematic analysis of the multi-factor coupling effects on fire spread. As a result, it is difficult to accurately predict the trend of fire spread and meet the demands of dynamic escape routes for three-dimensional rescue systems. In this study, a typical L-shaped building was used as the research object, and a parameterized fire scenario database was constructed using the FDS (Fire Dynamics Simulator) fire simulation software, combined with experimental data for multi-factor coupling analysis. By simulating various factors such as initial fire locations (stairwell or corridor corner), floor height of ignition (low/mid/high area), and wind direction, this study systematically reveals the dynamic evolution process of smoke diffusion and the spatial distribution characteristics and interaction mechanisms of fire smoke in indoor and outdoor three-dimensional spaces. It also focuses on the time-dependent variations of smoke propagation in indoor escape routes, staircases, and external walls. The results indicate that the L-shaped building causes asymmetric smoke diffusion. The fire spread mode is a result of multi-factor coupling effects at the fire scene. Safe evacuation decisions are directly related to fire spread characteristics, smoke diffusion paths, the location of trapped individuals, fire alarm occurrence time, and rescue methods. Minor changes in each parameter can lead to significant differences in evacuation outcomes. Based on the situation at the site, generating real-time, dynamic escape paths is a crucial guarantee for improving rescue efficiency and success rates. The findings provide scientific support for the design and optimization of human-machine collaborative rescue systems and offer a data foundation for fire risk assessment and emergency response planning.by Meirong Shan, Qian Guo, Ruofei Li, Ni Li, Yanhua Fu, Huanyu Qi, Ge Zhang, Qian Wang, Xingli Xu, Jinchuan Lai
Hypertension is one of the main causes of cardiovascular diseases worldwide, affecting over one billion people. Although aliskiren offers a valuable option for inhibiting the renin-angiotensin system, its safety profile in the real world remains insufficiently explored, especially for rare or under-recognized adverse events (AEs), which have not been fully clarified. Therefore, leveraging large-scale post-marketing surveillance data is crucial for identifying rare AEs and guiding safer clinical practice. This study aims to elucidate pharmacovigilance signals associated with aliskiren (an antihypertensive drug) by systematically analyzing the characteristics of adverse events (AEs) from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and WHO-VigiAccess database, which provides a reliable scientific basis for clinical practice and regulatory decision-making. We conducted a retrospective quantitative analysis of aliskiren-related AE reports from the aforementioned two databases, employing the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) algorithms for signal detection. The results indicate that there were 5,596 and 5,549 aliskiren-related reports in the FAERS and WHO-VigiAccess databases, respectively. The median duration of these AEs during the observation period was 62 days, with an interquartile range (IQR) of 7–282 days. In both databases, signals for aliskiren were distributed across 28 System Organ Classes (SOCs), among which investigations, cardiac disorders, renal and urinary disorders, vascular disorders, and metabolism and nutrition disorders exhibited significant signals based on specific criteria applied across the four algorithms. A total of 607 preferred terms (PTs) with significant disproportionality signals were detected using the four algorithms, including potential AEs not previously well-documented, such as palpitations, myalgia, proteinuria, muscular weakness, pulmonary edema, and pollakiuria. This study not only confirms the known adverse reactions of aliskiren but also uncovers new potential risks, highlighting the importance of strengthening drug safety monitoring to enhance therapeutic efficacy and reduce the risk of adverse reactions. It provides valuable safety insights for physicians considering the use of aliskiren in the management of primary hypertension.by Hang Sun, Haozhi Xu, Junying Li, Xiaoman Xie, Junmei Zhang, Hongjie Dong, Huanhuan Xie, Qi Wang, Guihua Zhao, Kun Yin, Jingyu Yang, Jianwei Zhou, Ruili Wu, Chao Xu
Gastric cancer (GC) is one of the most common and lethal cancers globally. methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) RNA methylation plays a crucial role in tumor initiation and progression by regulating RNA function. STM2457, a highly efficient METTL3 inhibitor, can inhibit METTL3 activity and may serve as a potential therapeutic strategy in cancers. However, the role of STM2457 for GC cells is still unknown. In this study, we analyzed the expression profile data of GC in TCGA and GEO databases, and further explored the expression involvement of METTL3 in GC cell line, investigated the therapeutic effect of STM2457 targeted inhibition of METTL3 in GC both in vitro and in vivo experiments. The results indicated that STM2457 could suppress GC cell proliferation and migration by inhibiting METTL3, and also promoted cell apoptosis and arrest the cell cycle in S phase. In addition, STM2457 could inhibit tumor growth in subcutaneous xenotransplantation mouse model. Our findings suggested that STM2457 had great potential for the treatment of GC and could serve as a foundation for future clinical applications.by Siyu Xie, Qiang Gu, Guiyin Zhuang, Xiaojing Guo, Bo Sun
ObjectivesTo explore the pharmacotherapeutic efficacy of heparin in the management of meconium-induced acute lung injury (ALI) in near-term newborn rabbits subjected to mechanical ventilation (MV) and ancillary respiratory medications.
MethodsNewborn rabbits at 30-day gestation (term 31 days) were anesthetized, intratracheally intubated and received human meconium-saline suspension, followed by parallel MV with individually adjusted tidal volume in a multi-plethysmograph-ventilator system. When ALI was induced after initial 3-h MV, therapeutic effects of single or combined subcutaneous heparin (100 U/kg), surfactant (200 mg/kg), and inhaled nitric oxide (iNO, 10 ppm), were compared for lung protective ventilation and survival as outcome, analyzed with linear regression models.
ResultsSignificantly reduced respiratory compliance by meconium was reinstalled during ensuing 7-h MV, with improved survival, among the treatment groups. The impact was verified by lung injury severity, surfactant phospholipid pools, and multiple mRNA expressions of surfactant proteins, lung fluid clearance-related factors, inflammatory mediators, growth factors, endothelial cell injury and coagulation-related factors as subphenotyping biomarkers. The overall benefits of heparin alone, or exerted with the dual and triple regimens, were discernible by both generalized linear model and Cox proportional hazard ratio regression for survival and other major variables as outcome. Its adverse effects were intangible.
ConclusionThe comparable efficacy of heparin, alongside the PS and NO, was corroborated in attenuating meconium-mediated, ventilator-induced ALI, which should warrant clinical investigation to validate.
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.
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