This article provides a systematic interpretation and review of the Society of Critical Care Medicine 2024 Guidelines on Adult ICU Design. Developed based on the Grading of Recommendations Assessment, Development and Evaluation methodology, the guideline address five core themes: ICU layout, room design, infection control, infrastructure, and staff spaces, and put forward 17 evidence-based recommendations, including 5 good practice statements. This article briefly introduces the guideline development methods and evidence characteristics, and focuses on summarizing key recommendations, including high-visibility layouts, single-bed ward settings, natural lighting and noise reduction strategies, integrated infection prevention and control design, remote monitoring, and flexible capacity expansion capabilities. Furthermore, it delves into the applicability and localized implementation pathways within China's healthcare environment, analyzing limitations in terms of evidence quality, specialty applicability, and cost-effectiveness. Furthermore, by integrating the Chinese Guidelines for the Construction and Development of Critical Care Medicine (2025 Edition) and current domestic practices, the article proposes tiered and phased implementation recommendations. This article aims to provide domestic healthcare institutions with a scientific reference that balances international cutting-edge concepts with China's real-world conditions for the construction and renovation of ICUs, thereby promoting the development of intensive care environments centered on patient safety, healthcare worker well-being, and infection control.

ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); however, its underlying neurological pathogenic mechanisms remain incompletely understood. Endogenous formaldehyde (FA), a metabolic byproduct of methylation-demethylation cycles, has recently been implicated in neurotoxicity, oxidative damage, and cognitive impairment. This study aimed to investigate whether excessive FA contributes to myelin sheath demyelination in mice and to evaluate the protective effects and mechanisms of two FA-elimination strategies: sodium bisulfite (NaHSO₃), a classical FA scavenger, and polyethylene glycol-modified astaxanthin nanoparticles (PEG-ATX@NPs), a brain-targeted nano-antioxidant formulation. MethodsA chronic demyelination model was established by feeding female C57BL/6J mice a diet containing 0.2% cuprizone (CPZ) for four weeks, followed by a two-week intervention period. Eighty mice were randomly assigned to four groups: NS (normal saline), CPZ+NS, CPZ+NaHSO₃, and CPZ+PEG-ATX@NPs. Behavioral tests, including open-field, Y-maze, and pole-climbing assays, were conducted to assess locomotor activity, motor coordination, and working memory. FA levels in serum, corpus callosum, and spinal cord were measured using an Na-FA fluorescent probe and quantified via in vivo and ex vivo fluorescence imaging. Neuroinflammatory responses were evaluated by measuring TNF-α, IL-1β, and IL-6 levels using ELISA, while oxidative stress was assessed by reactive oxygen species (ROS) fluorescence intensity. Demyelination was examined via Luxol fast blue staining, and microglial activation was analyzed by Iba1 immunofluorescence. Correlation analyses were performed to explore relationships among FA levels, inflammatory cytokines, ROS intensity, and behavioral parameters. ResultsCompared with the NS group, mice in the CPZ+NS group exhibited significant weight loss, impaired motor coordination and memory, and markedly reduced myelin regeneration (P<0.05). FA levels and pro-inflammatory cytokines were significantly elevated in serum, corpus callosum, and spinal cord (P<0.05). FA-associated fluorescence in brain and spinal tissues, as well as ROS intensity across all tissues examined, also increased substantially (P<0.05). CPZ treatment induced pronounced microglial activation and severe demyelination in the corpus callosum (P<0.01). Both NaHSO₃ and PEG-ATX@NPs effectively reduced FA accumulation in the brain and spinal cord, attenuated demyelination, suppressed microglial activation, decreased inflammatory cytokine levels, and improved motor and cognitive performance. These results confirm that CPZ induced severe demyelination accompanied by oxidative stress, neuroinflammation, and abnormal FA accumulation. Following intervention with either NaHSO₃ or PEG-ATX@NPs, endogenous FA levels in the CNS were substantially reduced. Both treatments alleviated demyelination and significantly decreased the number of activated microglia. Levels of TNF-α, IL-1β, and IL-6 in serum, corpus callosum, and spinal cord were downregulated. Behavioral performance improved significantly, as evidenced by enhanced locomotor activity, better coordination, and improved memory function. These findings indicate that both FA-scavenging agents mitigate CPZ-induced biochemical and behavioral abnormalities. ConclusionThis study demonstrates that excessive endogenous FA is closely associated with cognitive impairment, inflammatory dysregulation, and demyelination in a CPZ-induced chronic demyelination mouse model. Clearing abnormally elevated FA effectively reduces neuroinflammation, suppresses microglial overactivation, decreases oxidative stress, and alleviates demyelination, ultimately improving motor and cognitive outcomes in mice. These results suggest that targeting endogenous FA represents a promising therapeutic strategy for MS and other demyelinating disorders. Further investigations are warranted to explore the long-term safety, dosage optimization, and molecular pathways involved in FA-mediated neurotoxicity.

ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); however, its underlying neurological pathogenic mechanisms remain incompletely understood. Endogenous formaldehyde (FA), a metabolic byproduct of methylation-demethylation cycles, has recently been implicated in neurotoxicity, oxidative damage, and cognitive impairment. This study aimed to investigate whether excessive FA contributes to myelin sheath demyelination in mice and to evaluate the protective effects and mechanisms of two FA-elimination strategies: sodium bisulfite (NaHSO₃), a classical FA scavenger, and polyethylene glycol-modified astaxanthin nanoparticles (PEG-ATX@NPs), a brain-targeted nano-antioxidant formulation. MethodsA chronic demyelination model was established by feeding female C57BL/6J mice a diet containing 0.2% cuprizone (CPZ) for four weeks, followed by a two-week intervention period. Eighty mice were randomly assigned to four groups: NS (normal saline), CPZ+NS, CPZ+NaHSO₃, and CPZ+PEG-ATX@NPs. Behavioral tests, including open-field, Y-maze, and pole-climbing assays, were conducted to assess locomotor activity, motor coordination, and working memory. FA levels in serum, corpus callosum, and spinal cord were measured using an Na-FA fluorescent probe and quantified via in vivo and ex vivo fluorescence imaging. Neuroinflammatory responses were evaluated by measuring TNF-α, IL-1β, and IL-6 levels using ELISA, while oxidative stress was assessed by reactive oxygen species (ROS) fluorescence intensity. Demyelination was examined via Luxol fast blue staining, and microglial activation was analyzed by Iba1 immunofluorescence. Correlation analyses were performed to explore relationships among FA levels, inflammatory cytokines, ROS intensity, and behavioral parameters. ResultsCompared with the NS group, mice in the CPZ+NS group exhibited significant weight loss, impaired motor coordination and memory, and markedly reduced myelin regeneration (P<0.05). FA levels and pro-inflammatory cytokines were significantly elevated in serum, corpus callosum, and spinal cord (P<0.05). FA-associated fluorescence in brain and spinal tissues, as well as ROS intensity across all tissues examined, also increased substantially (P<0.05). CPZ treatment induced pronounced microglial activation and severe demyelination in the corpus callosum (P<0.01). Both NaHSO₃ and PEG-ATX@NPs effectively reduced FA accumulation in the brain and spinal cord, attenuated demyelination, suppressed microglial activation, decreased inflammatory cytokine levels, and improved motor and cognitive performance. These results confirm that CPZ induced severe demyelination accompanied by oxidative stress, neuroinflammation, and abnormal FA accumulation. Following intervention with either NaHSO₃ or PEG-ATX@NPs, endogenous FA levels in the CNS were substantially reduced. Both treatments alleviated demyelination and significantly decreased the number of activated microglia. Levels of TNF-α, IL-1β, and IL-6 in serum, corpus callosum, and spinal cord were downregulated. Behavioral performance improved significantly, as evidenced by enhanced locomotor activity, better coordination, and improved memory function. These findings indicate that both FA-scavenging agents mitigate CPZ-induced biochemical and behavioral abnormalities. ConclusionThis study demonstrates that excessive endogenous FA is closely associated with cognitive impairment, inflammatory dysregulation, and demyelination in a CPZ-induced chronic demyelination mouse model. Clearing abnormally elevated FA effectively reduces neuroinflammation, suppresses microglial overactivation, decreases oxidative stress, and alleviates demyelination, ultimately improving motor and cognitive outcomes in mice. These results suggest that targeting endogenous FA represents a promising therapeutic strategy for MS and other demyelinating disorders. Further investigations are warranted to explore the long-term safety, dosage optimization, and molecular pathways involved in FA-mediated neurotoxicity.

OBJECTIVE To compare the efficacy and safety of evolocumab and probucol in patients with ultra-high-risk atherosclerotic cardiovascular disease （ASCVD） following percutaneous coronary intervention （PCI）. METHODS A retrospective analysis was conducted on 156 ultra-high-risk ASCVD patients who underwent PCI in our institution between January 1， 2023 and December 31， 2024. According to the lipid-lowering regimen， the patients were categorized into evolocumab group （ n ＝86） and probucol group （ n ＝70）. Changes in lipid parameters [total cholesterol （TC）， low-density lipoprot ein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， triglycerides， lipoprotein （a）， and lipid goal achievement rate ] ， inflammatory markers [interleukin-6 （IL-6） and C-reactive protein （CRP） ] ， and cardiac function indices （left ventricular ejection fraction， left ventricular end-systolic diameter， left ventricular end-diastolic diameter， and N-terminal pro-B-type natriuretic peptide） were compared between two groups at baseline and after 6 months of treatment. The incidence of adverse clinical events during treatment， including acute myocardial infarction， in-stent restenosis， acute heart failure， cerebral hemorrhage， and stroke， was also evaluated. RESULTS No statistically significant differences were observed between the two groups at baseline （ P ＞0.05）. After 6 months of treatment， both groups demonstrated significant improvements in lipid profiles （except HDL-C） and inflammatory markers compared to those at baseline （ P ＜0.05）. The evolocumab group exhibited greater reductions in TC， LDL-C， IL-6， and CRP， along with a higher lipid target achievement rate， compared with the probucol group （ P ＜0.05）. There were no statistically significant differences in the cardiac function-related indicators before and after treatment between the two groups， nor in the incidence of adverse events during the treatment （ P ＞0.05）. CONCLUSIONS For ultra-high-risk ASCVD patients after PCI， both of the above treatment options are associated with improvements in blood lipid and inflammatory response， with good safety during short-term follow-up. Evolocumab shows superior efficacy in TC， LDL-C and inflammatory markers reduction and lipid target achievement， compared to probucol.

Objective To comprehensively analyze the current epidemic characteristics and disease burden of brucellosis in Tongliao City, and to provide a basis for the prevention and control strategy of brucellosis in Tongliao City. Methods The report data of brucellosis in Tongliao City from 2018 to 2023 were collected. Descriptive methods were used for data analysis, and the disability-adjusted life years and indirect economic losses were calculated. Results From 2018 to 2023, a total of 22 034 cases were reported in Tongliao City, with an average annual incidence of 136.17/100 000. The incidence was statistically different between men and women ( χ²=12.23, P=0.032). The majority of cases were farmers (94.25%), followed by herdsmen (1.67%). The age group was concentrated between 30-60 years old (79.30%), among which the majority of cases were in the 40-50 years group (6 883/22 034). The onset time had seasonal characteristics, and the peak period was from March to August (the seasonal index was between 115.40%-151.29%). In terms of regional distribution, cases were reported in all counties (banners). The average annual incidence was highest in Kulun Banner (233.85/100 000) and Zalut Banner (210.13/100 000), and lowest in Keerqin District (42.28/100 000) and Holingol City (31.87/100 000). The analysis of disease burden showed that a total of 677.55 person-years (YLD) were lost from 2018 to 2023, with an average annual loss of 112.92 person-years. The total indirect economic loss was 59.3576 million yuan, with an average annual loss of 9.892 9 million yuan, and the people over 60 years old had the lowest annual loss. Conclusion The overall brucellosis epidemic in Tongliao City has shown a fluctuating downward trend. The epidemic prevention and control should be strengthened in farmers, people aged 40-50 years old, and areas such as Zalut Banner and Kulun Banner to further control the epidemic of brucellosis.

Background Arsenic exposure has been demonstrated to induce apoptosis. The fibronectin type III structural domain 3B protein (FNDC3B) has been shown to promote cancer cell proliferation; however, its role in arsenic-induced apoptosis remains to be elucidated. Objective To investigate the effects of sodium arsenite (NaAsO₂) and its metabolites on the expression of FNDC3B gene in A549 cells and to understand the function of FNDC3B gene in A549 cells. Methods (1) A549 cells were exposed to varying final concentrations of NaAsO₂ and their optical density at 450 nm values were measured by Cell Counting Kit-8 (CCK-8) after 48 h. Survival curves were plotted, and a final exposure dose was selected according to the survival rate. Total protein and RNA were extracted by exposing A549 cells to high (30 µmol·L⁻¹), medium (20 µmol·L⁻¹), and low (10 µmol·L⁻¹) NaAsO₂ concentrations, high (30 µmol·L⁻¹) monomethylarsinic acid (MMA), and high (30 µmol·L⁻¹) dimethylarsinic acid for a period of 48 h. mRNA expression and the protein expression of the FNDC3B gene was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB), while the protein ubiquitination expression of the FNDC3B gene was detected by co-immunoprecipitation (CO-IP) and WB assay. (2) Knockdown of FNDC3B gene expression was achieved in A549 cells by siRNA interference. The si-FNDC3B fragment was transfected in A549 cells for 48 h. The mRNA and protein expression of FNDC3B gene was then detected by qRT-PCR and WB assay. Cell viability was determined through CCK-8 assay. Hoechst 33342/propidium iodide (PI) double staining and JC-1 mitochondrial membrane potential assay were employed to detect both early and late apoptosis, while cleaved caspase3 protein and P53 signalling pathway related protein expressions were evaluated by WB. Results (1) The CCK-8 results demonstrated a decline in the viability of A549 cells with an increase in NaAsO₂ concentration, with an inhibitory concentration at 50% of 38.12 µmol·L⁻¹. The qRT-PCR results demonstrated that compared to the control group, varying concentrations of NaAsO₂ (10, 20, and 30 µmol·L⁻¹) significantly upregulated the mRNA expression of FNDC3B gene (P<0.01). In contrast, MMA and DMA showed no significant effect on FNDC3B mRNA expression (P>0.05). The WB analysis revealed that the protein expression of FNDC3B was reduced in the NaAsO₂-treated group compared to the control, accompanied by elevated ubiquitination levels of FNDC3B protein, particularly at the K48 ubiquitination site. MMA and DMA exhibited no impact on FNDC3B protein expression. (2) Following the specific knockdown of FNDC3B expression in A549 cells, the CCK-8 assay demonstrated a significant reduction in cell viability in the silenced FNDC3B group (si-FNDC3B) compared to the control group. The JC-1 assay demonstrated that the mitochondrial membrane potential was diminished in the si-FNDC3B group relative to the control group. The Hoechst 33342/PI staining assay revealed that the si-FNDC3B group exhibited a notable degree of apoptosis. The si-FNDC3B group also displayed substantial apoptosis. The WB analysis indicated that the relative expressions of cleaved caspase3, P53, MDM2, Bad, and Bax proteins were elevated in the si-FNDC3B group in comparison to the control group. Conclusion The presence of NaAsO₂ is observed to promote the ubiquitination expression of the FNDC3B protein, which in turn reduces the expression of FNDC3B protein. However, the main metabolites DMA and MMA have no effect on the expression of FNDC3B. Furthermore, the silencing of FNDC3B is observed to inhibit the viability of A549 cells and promote apoptosis, a phenomenon related to the activation of P53 signaling pathway.

BACKGROUND:Leonurine has many biological activities such as improving microcirculation,anti-oxidation,anti-apoptosis,scavenging free radicals,anti-inflammation,and anti-fibrosis,and can promote osteogenic differentiation of bone marrow mesenchymal stem cells,which has the potential to be applied in the treatment of periodontitis. OBJECTIVE:To explore the anti-inflammatory and osteogenic effects of leonurine loading into chitosan/sodium glycerophosphate/sodium alginate hydrogel. METHODS:(1)Chitosan/sodium glycerophosphate/sodium alginate hydrogel(blank hydrogel)and chitosan/sodium glycerophosphate/sodium alginate/leonurus alkali hydrogel were prepared respectively.RAW 264.7 and MC3T3-E1 cells were inoculated with the two kinds of hydrogel.The cytotoxicity of hydrogels was detected by CCK-8 assay and live/dead cell staining.(2)RAW 264.7 cells were cultured in five groups.The blank group was cultured for 24 hours routinely.The lipopolysaccharide group was treated with lipopolysaccharide.The simple hydrogel group was treated with lipopolysaccharide and blank hydrogel.The drug-loaded hydrogel group was treated with lipopolysaccharide and drug-loaded hydrogel.The inhibitor group was treated with lippolysaccharide,drug-loaded hydrogel,and PI3K inhibitor LY294002.24 hours later,mRNA expression of inflammation-related factors was detected by qRT-PCR.Western blot assay was utilized to detect the protein expression of inflammation-related factors and PI3K/AKT signaling pathway.(3)MC3T3-E1 cells were inoculated in four groups.The blank group was cultured without any material.The simple hydrogel group was treated with blank hydrogel.The drug-loaded hydrogel group was treated with drug-loaded hydrogel.The inhibitor group was treated with drug-loaded hydrogel and PI3K inhibitor LY294002 for 7 days.Alkaline phosphatase staining was performed.mRNA expression levels of osteogenic factors were detected by qRT-PCR.The protein expression levels of the PI3K/AKT signaling pathway were detected by western blot assay. RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead cell staining showed that the two kinds of hydrogels had no cytotoxic effect and had good cytocompatibility.(2)Compared with the blank group,the mRNA and protein expression levels of interleukin 6,tumor necrosis factor α,and interleukin 1β were significantly increased(P<0.05),and the protein expression levels of p-AKT,p-PI3K,p-p65,and p-IκBα were significantly increased in the lipopolysaccharide group(P<0.05).Compared with lipopolysaccharide group,mRNA and protein expression levels of the above indexes were decreased in drug-loaded hydrogel group(P<0.05).Compared with the drug-loaded hydrogel group,the mRNA and protein expression levels of the above indexes were decreased in the inhibitor group(P<0.05).(3)The activity of alkaline phosphatase in drug-loaded hydrogel group was higher than that in the blank group,simple hydrogel group,and inhibitor group(P<0.05).Compared with blank group,the mRNA expression levels of alkaline phosphatase,Runx2,osteocalcin,and type I collagen were increased(P<0.05),and the protein expression levels of p-AKT and p-PI3K were increased in the simple hydrogel group(P<0.05).Compared with the simple hydrogel group,the mRNA and protein expression levels of the above indexes were increased in the drug-loaded hydrogel group(P<0.05).Compared with the drug-loaded hydrogel group,the mRNA and protein expression levels of the above indexes were decreased in the inhibitor group(P<0.05).(4)These findings conclude that chitosan/sodium glycerophosphate/sodium alginate/leonurine hydrogel has anti-inflammatory and osteogenic effects,which may be related to the regulation of PI3K/AKT signaling pathway.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

OBJECTIVE: To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. METHODS: A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using "SETD1B" and "epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. RESULTS: The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely c.5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+PM2_Supporting+PP2+PP3). The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no significant difference in incidence between males and females. CONCLUSION SETD1B gene variants may cause neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.
Humans ; Female ; Child ; Epilepsy/genetics* ; Language Development Disorders/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Exome Sequencing ; Male