Background The widespread use of herbicides has led to environmental contamination and has implications for human health. The liver is an important organ for the detoxification of environmental pollutants; however, studies on the association between herbicide exposure and liver function are limited. Objectives To investigate the association between baseline serum herbicide levels and changes in liver enzyme levels and liver enzyme abnormalities over a 5-year period in middle-aged and older adults. Methods This study was based on a nested case-control population of type 2 diabetes established in the Dongfeng-Tongji cohort, with a total of 1388 subjects included in this study and followed up for 5 years. Epidemiological data were collected through questionnaires, and baseline serum concentrations of three herbicides (metolachlor, propham, and acetochlor) were measured by gas chromatography-triple quadrupole mass spectrometry. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were detected at baseline and follow-up visits. The associations between baseline serum herbicide levels and changes in AST and ALT over 5 years were assessed using linear regression models with herbicide levels categorized into quartiles, adjusting for age, sex, education level, smoking status, drinking status, physical activity, body mass index, and new-onset type 2 diabetes occurred during follow-up. The relationship between baseline serum herbicide levels and the risk of liver enzyme abnormalities during follow-up was further analyzed using logistic regression models. Results The positive rates of metolachlor, propham, and acetochlor were all higher than 80%, and their spiked rates of recovery ranged from 73.46% to 106.77%. The mean ± standard deviation of the age of subjects at baseline was (62.7±7.6) years, with 34.1% being male. The median serum levels of metolachlor, propham, and acetochlor at baseline were 0.05, 0.16, and 0.03 ng·mL⁻¹, respectively. There was no significant difference in baseline serum herbicide levels between the normal and abnormal liver enzyme groups at follow-up (P >0.05). The baseline liver enzyme levels and the changes in AST and ALT over 5 years in those who developed abnormal liver enzymes were significantly higher than those in the normal liver enzyme group (P <0.05). The linear regression analysis showed that the changes in AST increased progressively over 5 years in the second, third, and fourth quartiles of propham compared to the lowest quartile group (the second quartile: b=1.49, 95%CI: 0.10, 2.87; the third quartile: b=1.52, 95%CI: 0.14, 2.90; the fourth quartile: b=1.69, 95%CI: 0.31, 3.08; P <0.05). The associations of serum metolachlor and acetochlor with changes in AST were not significant. Additionally, no significant relationships were found between the three serum herbicides and the changes in ALT over 5 years or the risk of liver enzyme abnormalities. Conclusion Serum propham levels in middle-aged and older adults are positively associated with changes in liver enzyme AST, which may have an effect on liver function. More studies are needed to provide scientific evidence for the association between herbicide exposure and liver function.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Mesenchymal stem cells(MSCs)hold great promise in regenerative medicine due to their multi-lineage differentiation potential and immunomodulatory properties.However,their functional heter-ogeneity and strong dependency on the microenvironment remain major challenges for clinical application.In recent years,the combination of single-cell transcriptome sequencing(scRNA-seq)and spatial tran-scriptomics sequencing(ST-seq)has provided revolutionary tools for systematically deciphering the heter-ogeneity,functional diversity,and microenvironmental interactions of MSCs.Using scRNA-seq,re-searchers have successfully resolved the functional heterogeneity of MSCs and identified key functional subpopulations,such as pro-angiogenic,immunoregulatory,and matrix-remodeling subsets.Meanwhile,ST-seq has revealed the distinct spatial distribution of MSCs within tissues and their dynamic interaction networks with the microenvironment.The integration of these two technologies has not only enabled the construction of a three-dimensional"identity-location-function"atlas of MSCs,but also uncovered spatio-temporal dynamic regulatory mechanisms of specific subpopulations during tissue repair.Looking forward,the combination of ultra-high-resolution ST-seq platforms such as Xenium,multi-omics integration,and artificial intelligence-driven analysis will shift MSCs research from descriptive studies toward precise inter-vention,offering new strategies for functional subpopulation screening and microenvironment reprogram-ming therapy.This review systematically summarizes the latest advances in scRNA-seq and ST-seq tech-nologies in MSC research,discusses their applications in elucidating cellular heterogeneity,spatial micro-environment,and clinical translation,and provides a theoretical basis and technical guidance for preci-sion treatment in regenerative medicine.

Progressive symmetric erythrokeratodermia(PSEK)is a rare hereditary skin disease charac-terized by symmetrical erythema,hyperkeratosis and multiorgan lesions.Its clinical phenotypes are highly heterogeneous and may be accompanied by symptoms such as thrombocytopenia,which can be fatal in se-vere cases.The genotype-phenotype association mechanism of PSEK is extremely complex.Currently,it is known that mutations in multiple genes such as GJB3,KDSR,and KRT83 can cause the disease.A-mong them,3-ketodihydrosphingosine reductase(KDSR)has been found to harbor nearly 20 clinical mu-tations.These mutations interfere with the de novo ceramide synthesis pathway,disrupt the homeostasis of the skin barrier,and cause platelet production disorders and multi-organ lesions,making it a current research hotspot in the molecular mechanism of PSEK.The pathogenic mutations of KDSR are widely and uniformly distributed throughout the entire protein,rather than being limited to the traditionally recog-nized active center,suggesting that the impairment of the KDSR enzymatic activity is not the only cause of PSEK.In view of this,this study selected four typical mutants of KDSR(KDSRQG55-56R,KDSRn38C,KDSRY186F,KDSRG182S),and first used recombinant expression technology to prepare pure and homoge-neous mutant proteins.Subsequently,thermal stability experiments as well as oligomerization analysis were conducted on these four mutant proteins.The results showed that the Tm values of the four mutants were significantly lower than that of the wild type.Particularly,KDSRF138C and KDSRQG55-56R were nearly completely denatured at physiological temperature.This result was perfectly consistent with the further Rosetta energy analysis.In conclusion,this study took several pathological mutations of the PSEK patho-genic factor KDSR as the research object and discovered that the conformational stability of KDSR might be closely related to the occurrence of PSEK pathogenicity,indicating that the imbalance of conformation-al homeostasis is very likely to be one of the common contributing factors of many genetic diseases,inclu-ding PSEK.This provides a new theoretical basis and reference for explaining the molecular mechanism of genotype-phenotype heterogeneity in many genetic diseases.

Objective To explore the damage results and structural response laws of medical cabins in ships under explosion attack.Methods Firstly,the cabin structure was equivalently regarded as a T-shaped plate frame based on the explosion load theory,then four finite element models for the medical cabins were established with the dimensions(length ×width×height)of 2.8 m×2.6 m×2.3 m,3.2 m×3.2 m×2.4 m,4.2 m×3.2 m×2.5 m and 5.4 m×4.0 m×2.6 m.Secondly,an explosion damage model was constructed using ABAQUS simulation software,and explosion damage simulation was carried out with the explosion locating at the cabin center and the outside of the bulkhead and the explosion energy of 10 kg and 100 kg trinitrotoluene(TNT)equivalent.Finally,the 10 kg and 100 kg TNT explosion damage results were ananlyzed at the cabin center and the outside of the bulkhead.Results At the cabin center,10 kg TNT explosion resulted in local deformation and limited affected area of the large-sized cabin,while 100 kg TNT explosion lead to extensive affected ranges in the functional areas and severe deformation and damage in the small-sized cabin.At the outside of the bulkhead,10 kg TNT explosion gave rise to breaches in some areas of the small-sized cabin and local deformation of the large-sized cabin,while 100 kg TNT explosion caused large breaches in all the cabins.Conclusion The explosion load induces serious deformation and damage and complicated breaches in the cabin with small size and weak structural strength.The cabin with large size and thick bulkhead and stiffener behaves well in explosion resistance,while high equivalent explosions may bring about serious damage to its local structure.[Chinese Medical Equipment Journal,2025,46(1):27-32]

This studyobtained the proteins of virulence factors EsxA and EsxB from Mycobacterium haemophilum and explored their interactions both in vitro and in vivo.The aim was to lay a foundation for further analysis of the functional mechanisms of EsxA and EsxB,and to further the development of drugs targeting Mycobacterium haemophilum.On the basis of bioinformatics analysis of the virulence factors EsxA and EsxB from Mycobacterium haemophilum,we performed molecular cloning,using Mycobacterium haemophi-lum as a template to construct recombinant plasmids EsxA-pGl01,EsxB-pGl01,and EsxB-pET-29b.The proteins of EsxA,EsxB,and their complex were expressed with a prokaryotic system,then purified through nickel-affinity chromatography and gel filtration chromatography.Intracellular colocalization was determined through fluorescence colocalization.Prokaryotic expression systems for EsxA,EsxB,and their complex were successfully constructed,and purified proteins were obtained.Fluorescence colocalization indi-cated that EsxA and EsxB interacted in vivo.In vivo fluorescence colocalization and in vitro complex formation suggested that EsxA and EsxB interacted both intracellularly and extracellularly.Our findings lay a foundation for studying the pathogenic mechanisms of the virulence factors EsxA and EsxB in Mycobacterium haemophilum,and performing structural analysis of their complex.

Ankylosing spondylitis(AS)is a chronic autoimmune disease characterized by inflammatory involvement of the axial skeleton and pathological bone formation.The T helper 17 cell(Th17 cell)subset of lym-phocytes plays a central role in mediating the inflammatory processes associated with AS.This review summarizes recent advances in the regulation of Th17 cell differentiation in AS,with a focus on the complex mechanisms governed by cytokine microenvironments,transcription factor networks,and metabolic and epigenetic regulatory pathways.Key regulatory components discussed include the IL-23/STAT3 signaling axis,the CCL20/CCR6 chemo-tactic axis,and the master transcription factor RORγt.Additionally,this review critically evaluates emerging thera-peutic strategies targeting metabolic reprogramming(e.g.,PKM2),epigenetic regulators(e.g.,JMJD3,EZH2),engineered exosome delivery systems,and modulators of metabolic enzymes.By analyzing the limitations of current treatment approaches,the review proposes future research directions emphasizing multi-target therapeutic strategies and highlights the importance of personalized medicine in achieving precise and effective treatment for AS.These developments reveal promising new avenues for modulating Th17-mediated immunity,offering transformative poten-tial for the clinical management of AS.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Objective To explore the abnormal expression of the MT-ND family in pan-cancers and its prognostic value.Methods Transcriptome expression and clinical data of 33 cancers were downloaded from the TCGA database,thereby analyzing the expression differences of the MT-ND family in tissuesof different types of cancers and normal tissues.The prognostic role of the MT-ND family in pan-cancers was explored by univariate Cox regression analysis and Kaplan-Meier survival analysis.Results The expression of the MT-ND family was upregulated in the kidney chromophobe,acute myeloid leukemia and thymoma,and downregulated in the remaining tumors.The expression of the MT-ND family was associated with the overall survival rate of different types of cancers.In addition,the MT-ND family were significantly correlated with the immune invasion subtypes,and were correlated with stromal cell invasion and tumor cell stemness to varying degrees.The expression of MT-ND4 was downregulated in brain lower grade glioma,which was a protective factor for prognosis;while the expression of MT-ND4 in thymoma was upregulated,which was a risk factor for prognosis.Conclusion Pan-cancer analysis has confirmed that the MT-ND family can predict the tumor prognosis,which provides new ideas and strategies for the precision treatment and prognostic management of cancer.

Objective To evaluate the efficacy of cefoperazone-sulbactam(CS)combined with ulinastatin in the treatment for stroke-associated pneumonia(SAP)after endovascular treatment of acute large vessel occlusive stroke(AIS-LVO).Methods This study retrospectively included patients who developed SAP after endovascular treatment of AIS-LVO admitted to the intensive care unit of the Department of Neurology at the First Affiliated Hospital of Xi'an Jiaotong University from March 2022 to December 2023.Patients were randomly divided into the ulinastatin group(combined application of ulinastatin and CS)and the control group(sole application of CS)using a random number table.Baseline and clinical data,including sex,age,infarct laterality,culprit vessel,trial of Org 10172 in acute stroke treatment(TOAST)classification,baseline National Institutes of Health stroke scale(NIHSS)score,baseline Glasgow coma scale(GCS)score,medical history(hypertension,diabetes,coronary heart disease,atrial fibrillation,past history of stroke),history of smoking and alcohol consumption,admission baseline blood pressure,laboratory test results at admission(including red blood cell count,white blood cell count,neutrophil count,platelet count,random blood glucose levels,albumin,creatinine,low-density lipoprotein cholesterol,uric acid,and D-dimer),and endovascular therapies(including mechanical retrieval of thrombus,stenting,balloon dilatation,arterial thrombolysis and combination therapy)were collected from both groups.After the diagnosis of SAP,patients in both groups underwent conventional treatment such as sputum expectoration and clearance,antipyretic and antitussive treatment,oxygen therapy,respiratory support,fluid and nutrition support,along with CS anti-infective therapy.In contrast to the control group,the ulinastatin group additionally received continuous ulinastatin treatment for at least 7 days.The adverse reactions of the two groups after initiating SAP treatment including allergic reactions(such as sudden dyspnea,skin redness,and shock),decrease in peripheral white blood cell count(below 4.0 × 109/L),nausea and vomiting,diarrhea,rash and/or itching,and liver enzymes(aspartate aminotransferase or alanine aminotransferase)elevation(more than twice the upper limit of normal)were compared between the two groups.The efficacy indicators encompassing arterial blood gas analysis(oxygenation index)and inflammatory factor indicators(interleukin-6[IL-6],procalcitonin)after 7 days of SAP treatment,pneumonia-related symptoms and signs before and after SAP treatment(including body temperature,heart rate,respiratory rate,sputum volume and characteristics,changes in lung rales,etc.),imaging examinations(such as head CT and chest CT).The evaluation of therapeutic efficacy is classified as(1)markedly effective:following treatment,significant relief was observed on pneumonia-related symptoms and signs,with body temperature returned to normal,and arterial blood gas analysis and inflammatory factor indicators returned to normal levels;post-treatment imaging studies reveal that over 2/3 of lung inflammation has been absorbed;(2)effective:after treatment,some improvement was observed in pneumonia-related symptoms and signs,with mild improvement in arterial blood gas analysis and inflammatory factor indicators;post-treatment imaging studies reveal some absorption of lung inflammation;(3)ineffective:no improvement or further deterioration of pneumonia-related symptoms,arterial blood gas analysis,and inflammatory factor indicators after treatment.The arterial blood gas analysis,inflammatory factor indicators and efficacy indicators were evaluated and compared between the control and the ulinastatin group.Compare the prognosis(improvement of the lesion in the chest CT after 7 days of treatment,length of stay in the intensive care unit,total length of hospital stay,and modified Rankin scale[mRS]score assessed via telephone follow-up or outpatient revisit 90 days after endovascular treatment[with an mRS score ≤2 indicating a good prognosis],as well as mortality).Results A total of 99 patients with AIS-LVO who developed SAP after endovascular treatment were included in this study,with 69 males(69.7％)and 30 females(30.3％),and an average age of(68±10)years.Among them,there were 46 cases in the ulinastatin group and 53 cases in the control group.(1)No statistically significant differences were observed in baseline or clinical characteristics between the two groups(all P＞0.05).(2)The overall effective(markedly effective and effective)rate of SAP treatment was greater in the ulinastatin group than that in the control group(89.1％[41/46]vs.69.8％[37/53],P=0.019).(3)No statistically significant differences were observed in serum IL-6 levels,procalcitonin levels,or arterial oxygenation index between the ulinastatin group and the control group before treatment(all P＞0.05).seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[64.39±52.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.31±0.20]μg/L)in the ulinastatin group were significantly lower compared to those before treatment(all P＜0.01),and the arterial oxygenation index was significantly higher than that before treatment([359.35±92.56]mmHg vs.[273.34±95.65]mmHg,P＜0.01).Seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[31.90±21.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.26±0.24]μg/L)in the ulinastatin group were significantly lower than those in the control group(all P＜0.01),and the arterial oxygenation index was significantly higher than that of the control group([359.35±92.56]mmHg vs.[314.81±81.97]mmHg,P=0.020).(4)In the ulinastatin group,there was 1 case of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 6.5％(3/46).In the control group,there were 2 cases of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 7.5％(4/53).No statistically significant differences were observed in the adverse reaction rate between the two groups(P＞0.05).(5)After 7 days of treatment,the ulinastatin group exhibited a greater improvement rate in chest CT lesions compared to the control group(93.5％[43/46]vs.77.4％[41/53],P=0.026).No statistically significant differences were observed between the two groups in terms of the length of stay in the intensive care unit or the total length of hospital stay(both P＞0.05).Additionally,the 90-day mortality rate after intravascular treatment was lower in the ulinastatin group compared to the control group(6.5％[3/46]vs.20.8％[11/53],P=0.040).No statistically significant differences were observed in the good prognosis rate between the two groups(P=0.119).Conclusions Combined treatment with CS and ulinastatin can improve the clinical symptoms,inhibit inflammatory factors and reduce mortality rate in SAP patients after receiving endovascular treatment for AIS-LVO.The results of this study still need to be further confirmed by large-scale prospective studies.