Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

Objective To evaluate the changes of perivascular space(PVS)in patients with subacute ischemic stroke(IS),as well as the relationship between PVS and cognitive dysfunction in IS patients,and to analyze the relationship between PVS indicators and cognitive function in subacute IS patients of different ages.Methods A total of 44 healthy controls(HC)and 39 patients with subacute IS were prospectively included.Automated quantitative analysis of MRI data was conducted to determine pPVS in the white matter and subcortical regions.Differences in pPVS between patients with subacute IS and HC were compared.Correlations between age,pPVS,and cognitive dysfunction were analyzed and modeled.Results Compared with the HC,the white matter pPVS in patients with subacute IS was significantly reduced(t=-2.21,P=0.031).In patients with subacute IS,the white matter pPVS showed a significant positive correlation with lesion volume(r=0.42,P=0.030)and mini-mental state examination(MMSE)scores(r=0.44,P=0.018).Both white matter pPVS(r=-0.42,P=0.010)and MMSE scores(r=-3.82,P=0.000 7)were negatively correlated with age.When age was over 61.35 years,there was a positive correlation between the white matter pPVS and MMSE scores.Conclusion PVS are closely related to cognitive impairment in patients with subacute IS.Age is a significant modulating factor in the relationship between PVS and cognitive dysfunction.Early monitoring of PVS and targeting it for intervention may positively impact the improvement of cognitive dysfunction following IS.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.

Objective:To explore the effect of sacubitril/valsartan(LCZ696)on intestinal microbiota and serological parameters associ-ated with its derived metabolites in rats with right ventricular remodeling due to hypoxic pulmonary hypertension(HPH).Methods:A total of 24 male rats were randomly divided into Control group,Hypoxia group,and H-LCZ696 group.Since day 1,the rats in the H-LCZ696 group were given LCZ696 by gavage,while those in the other two groups were given normal saline by gavage,both for 4 con-secutive weeks.Related indicators were measured after experiment,including hemodynamics,color Doppler ultrasound of right heart,and right ventricular remodeling.Histopathological staining and transmission electron microscopy were used to observe tissue struc-tures;the metagenomics technique was used to analyze the characteristics and functional annotation of intestinal microbiota in the fe-ces of the rats;ELISA was used to measure the serological parameters of the metabolites derived from intestinal microbiota.Results:There was a significant difference in mean pulmonary arterial pressure(mPAP)between the three groups of rats(F=101.797,P=0.000).Compared with the Control group,the Hypoxia group had an increase in mPAP,a reduction in right ventricular function,and in-creases in the indicators for pulmonary vascular remodeling and right ventricular remodeling.Compared with the Hypoxia group,the H-LCZ696 group had a reduction in mPAP,an improvement in right ventricular function,and reductions in the indicators for pul-monary vascular remodeling and right ventricular remodeling.Trans-mission electron microscopy showed that the Hypoxia group had disordered myocardial myofibrils of the right ventricle and mitochon-drial swelling,while such ultrastructural damage was improved after LCZ696 intervention.The metagenomics analysis showed that the Hypoxia group had a reduction in the diversity of intestinal microbiota,with increases in the abundance of pathogenic bacteria(such as Proteobacteria,Prevotella,and Clostridium)and reductions in the abundance of probiotic bacteria(such as Lachnospiraceae and Lacto-bacillus),and such changes were partially reversed after LCZ696 intervention,with inhibition of the proliferation of pathogenic bacteria such as Clostridiales,the failure to restore the diversity of intestinal microbiota,and a further reduction in the abundance of some probi-otic bacteria(such as Lactobacillus).ELISA showed that compared with the Control group,the Hypoxia group had increases in the serum levels of pro-inflammatory metabolites,and compared with the Hypoxia group,the H-LCZ696 group had reductions in the se-rum levels of pro-inflammatory metabolites.Conclusion:LCZ696 can alleviate right ventricular remodeling in HPH and regulate pathogenic bacteria and serum pro-inflammatory metabolites,with a main therapeutic effect on the cardiovascular system and a regula-tory effect on intestinal microbiota.

Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.

Eukaryotic translation initiation factor 5A (eIF5A) is the only known protein in eukaryotes that contains a hydroxyputrescine lysine modification. Only the modified form of eIF5A is biologically active and is widely involved in protein translation, mRNA degradation, autophagy, and other intracellular processes. Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells transform into mesenchymal phenotype cells through a highly regulated program. It plays a key role in embryonic development, tissue regeneration, and wound healing. Based on its biological functions, EMT can be classified into three types: I, II, and III. Type III EMT is the core mechanism underlying malignant tumor cell invasion and metastasis. This EMT mechanism involves the canonical pathway induced by transforming growth factor-β (TGF-β) and is regulated by various growth factors (TRAF6, EGF, IGF, HGF, VEGF), transcription factors (Twist, Slug, NF-κB, E12/E47, SIP1, ZEB1, etc.), and signaling pathways such as Wnt/β-catenin and PEAK1. eIF5A can influence tumor cell proliferation, invasion, and metastasis by regulating EMT-related signaling pathways. The known signaling pathways through which eIF5A regulates EMT include the canonical Smad signaling pathway and non-canonical pathways such as Rho/Rac1, Twist, STAT3, and MAT1. Additionally, certain miRNA family members, such as miR-30b, miR-599, and miR-203, can bind to the 3'-UTR of eIF5A2, inhibiting its expression and subsequently suppressing the EMT process in cancer cells, including gastric cancer and colorectal cancer. GC7, an inhibitor targeting the key enzyme DHPS involved in eIF5A modification, has been shown to reverse the EMT mechanism in oral squamous cell carcinoma, lung cancer, and breast cancer by regulating cytokine-mediated signaling pathways, including HIF-1α, STAT3/c-MYC, and Twist. However, to date, no inhibitors directly targeting eIF5A have been developed. In recent years, the mechanism of eIF5A activation catalyzed by DHPS and DOHH has become increasingly clear. As the only protein involved in lysine deoxyhydroxymethylation, DHPS may play a more critical role than eIF5A in the overall signal transduction process. Through in-depth analysis of the DHPS protein structure and its active site, researchers have shifted their approach to DHPS inhibitor development from substrate analog inhibitors (such as GC7, CNI-1493, DHSI-15, etc.) to allosteric inhibitors (11g, 26d, 8m, GL-1, etc.). GC7 is not suitable for clinical trials due to its lack of specificity and low bioavailability, and the therapeutic potential of novel allosteric inhibitors has yet to be clarified. Therefore, there is a significant gap in the development of covalent drugs targeting DHPS for cancer treatment in clinical settings. This paper reviews the research progress on eIF5A in regulating EMT, focusing on the molecular mechanisms by which eIF5A influences tumor cell invasion and migration. It also discusses the characteristics and current limitations of inhibitors targeting the hypusine pathway, aiming to provide insights for studying tumor metastasis mechanisms and drug discovery.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

Objective To investigate the association of endometrial thickness(EMT)with obstetric and neonatal outcomes of monoparous pregnancy in fresh cleavage embryos transfer.Methods A total of 1 845 patients of monoparous pregnancy after fresh cleavage embryos transfer cycles from Jan 2016 to Mar 2022 at Shanghai First Maternity and Infant Hospital,Tongji Universtiy were analyzed retrospectively.Patients were categorized into three groups by EMT on transferation day:≤8 mm(group A),8-14 mm(group B)and≥14 mm(group C).The primary outcomes were preterm birth(PTB),birth weight and birth weight z-score,small-for-gestation age,large-for-gestation age,very low birth weight,low birth weight and macrosomia.The second outcomes were pregnancy and perinatal complications.The relationship between EMT and adverse neonatal outcomes was estimated by Logistic regression analysis.Results The rate of ectopic pregnancy was increased significantly in group A.No significant differences were found among the three groups in gestation age,birth weight,birth weight z-score,PTB,small for gestation age,large for gestation age,low birth weight,very low birth weight and macrosomia.Compared with group B,the odds of adverse neonatal outcomes did not show significant differences before and after adjustment in both group A and group C by Logistic regression analysis.Conclusion Thinner EMT in fresh cleavage embryos transfer is associated with higher rate of ectopic pregnancy,while it is not independently associated with adverse perinatal outcomes.