Background: Patients with coarctation of the aorta (CoA) and an interrupted aortic arch (IAA) may present with small mitral valves (MVs) and a reduced left ventricular (LV) volume. Biventricular repair (BVR) in these patients is dependent on adequate size of the left cardiac structures.Purpose: This study evaluated the impact of the hemodynamic characteristics of atrial septal defects (ASDs) on MV growth following surgical repair. Methods: We retrospectively reviewed the data of patients diagnosed with CoA or IAA between 2007 and 2024. The z score for MV size measured 6 months postoperatively (Z2) was compared with the preoperative MV size (Z1). The factors associated with MV growth were also studied. Results: A total of 161 patients with CoA or IAA were included. Transthoracic echocardiography was used to assess the MV and LV dimensions preoperatively and 6 months postoperatively. Of the cohort, 155 (96.3%) underwent initial BVR and 6 underwent single-ventricle palliation. MV z scores significantly increased following BVR (mean change: +0.45±1.35; P<0.001) but decreased after single-ventricle repair (-0.56±0.49, P=0.04). Multivariate analysis identified the initial MV z score and ASD pressure gradient as independent predictors of MV growth (R2=0.39). Conclusion Annular growth of the MV was not observed in patients who underwent single-ventricle palliation. In contrast, among patients who achieved BVR, those with a small preoperative MV annulus and low ASD pressure gradient demonstrated subsequent catch-up MV growth, suggesting that adequate left-sided preload is essential for MV development.

Objective To analyze the epidemiological distribution,microbiological characteristics,drug-resistance status,and risk factors for mortality in adult intensive care unit(ICU)patients with Klebsiella pneumoniae infection.Methods This multi-center prospective cohort study included ICU patients with suspected infection from 67 hospitals across 16 Chinese provinces/municipalities between July 1,2021 and December 31,2022.Clinical data and microbiological results were collected,and patients were divided into survival and non-survival groups according to their survival status and drug-resistance situation.Risk factors for mortality and drug resistance in ICU patients with Klebsiella pneumonia infection were determined through univariate and multivariate logistic regression analyses.Results A total of 2964 ICU-infected patients were enrolled,with 12 175 microbial specimens submitted for testing.Among these,487 specimens tested positive for Klebsiella pneumoniae.Ultimately,314 patients with Klebsiella pneumoniae infection were identified,primarily from lung infections,with a drug-resistance rate of 78.3%.The in-hospital mortality rate of ICU patients infected with Klebsiella pneumoniae was 19.8%.Univariate and multivariate logistic regression analyses revealed that older age(P=0.027),high drug-resistance rate(P=0.028),and low clinical-effectiveness rate(P<0.001)were independent risk factors for mortality in ICU patients infected with Klebsiella pneumoniae.Drug-resistance analysis showed that,compared with non-resistant cases,ICU patients with drug-resistant Klebsiella pneumoniae infection had lower pathogen-clearance rates(P=0.003),clinical-effectiveness rates(P=0.004),and antibiotic-effectiveness rates(P<0.010),and higher mortality rates(P=0.006).Patients with Klebsiella pneumoniae abdominal infection(P=0.003)and urinary tract infection(P=0.007)had higher drug-resistance incidences.There were no statistically significant differences in clinical-effectiveness rate,Klebsiella pneumoniae clearance,drug-resistance incidence,mortality rate,or hospital-stay length between patients with lung infection and those with non-lung infection of Klebsiella pneumoniae(P>0.05).Compared with patients with non-bloodstream infection,patients with bloodstream infection of Klebsiella pneumoniae had lower clinical-effectiveness rates(P=0.027)and higher mortality rates(P=0.021).Conclusions Older age,high drug-resistance rate,and low clinical-effectiveness rate are independent risk factors for mortality in ICU patients infected with Klebsiella pneumoniae.ICU patients with bloodstream infection of Klebsiella pneumoniae may have lower clinical-effectiveness rates and higher mortality rates.ICU patients with abdominal and urinary tract infections caused by Klebsiella pneumoniae are more likely to develop drug resistance.

Generative Artificial Intelligence ishows a broad application prospect in the field of healthcare and has become an important technical means to promote the development of medical informatization.It addresses the multi-faceted challenges of medical record documentation,including efficiency,quality,and doctor-patient communica-tion.It analyzes the adaptability and feasibility of Generative Artificial Intelligence in different clinical scenarios of intelli-gent medical record generation.Additionally,it explores the issues present in current applications and proposes corre-sponding solutions,providing references for the effective application and continuous optimization of Generative Artifi-cial Intelligence in medical record documentation.This provides a theoretical foundation for further expanding the appli-cation scenarios of automatic medical record documentation in China's healthcare industry.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Objective To explore the effects of CDP-diacylglycerol synthase 1(CDS1)on autophagy and amyloid deposition in hippocampal neurons of mice and the related mechanism.Methods Congo red and immunohistochemical staining were used to observe the amyloid deposition in hippocampus of amyloid precursor protein(APP)/presenilin 1(PS1)double-transgenic mice.Lentivirus-mediated overexpression of APP was induced in HT22 cells,and Congo red staining was used to observe the amyloid deposition in HT22 cells.The protein expression levels of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ and P62 in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were detected by Western blotting.The differential protein CDS1 was screened based on the hippocampal proteomics results of APP/PS1 double-transgenic mice.The expression of CDS1 protein in hippocampal tissue of APP/PS1 transgenic mice and APP-overexpressed HT22 cells was detected by Western blotting.After lentivirus-mediated APP overexpression in HT22 cells,CDS1 was overexpressed,and the protein expression levels of LC3-Ⅱ and P62 were detected by Western blotting.Results β-amyloid protein(Aβ)was deposited in the hippocampus of APP/PS1 mice and in HT22 cells overexpressing APP.The levels of LC3-Ⅱ and P62 protein in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were significantly increased.A differential metabolic pathway,glycerophospholipid metabolic pathway,was screened by Kyoto Encyclopedia of Genes and Genomes pathway analysis in the proteomic results of APP/PS1 double-transgenic mice,and the differential protein CDS1 was obtained.Compared with wild-type C57BL/6 mice,APP/PS1 double-transgenic mice exhibited a significantly decrease in CDS1 protein expression in the hippocampus(0.46±0.07 vs 1.00±0.25,P＜0.01).Similarly,lentivirus-mediated overexpression of APP in HT22 cells resulted in decreased CDS1 protein levels compared to cells infected with empty viral vector controls(0.68±0.18 vs 1.00±0.13,P＜0.01).The autophagy flow of nerve cells was significantly restored after the CDS1 overexpression in APP-overexpressed HT22 cells(LC3-Ⅱ:1.00±0.15 vs 0.21±0.05,P＜0.01;P62:1.00±0.16 vs 0.67±0.10,P＜0.01),and Aβ deposition was significantly decreased.Conclusion Downregulation of CDS1 expression can induce dysfusion of autophagosome and lysosome,promoting amyloid deposition in hippocampus of mice with Alzheimer's disease.

The continuous accumulation of plastic waste such as polyethylene in the environment has caused serious environmental pollution issues.Considering the high similarity in the molecular structure of petroleum and polyolefin,it is feasible to apply rare earth-zeolite catalysts in polyolefin plastic upcycling,which is commonly used in fluid catalytic cracking(FCC)in the field of petroleum refining.In this study,Ce-modified HY(Ce-HY)zeolites were synthesized and characterized by a series of analytical methods,such as high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM),Fourier infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),etc.When introducing 5% Ce species into HY zeolites,the 5Ce-HY showed excellent catalytic performance in the catalytic cracking of low-density polyethylene(LDPE),which achieved 98.4% LDPE conversion with 91.5% selectivity of gaseous alkanes at 300℃,and 75.4% of them were isoparaffins.In addition,the effect of the location of rare earth species in Y zeolites on the catalytic performance was explored by fine X-ray diffraction(XRD)in the range of 11°-13°and in situ-Raman analyses.The Ce species located in the supercage of Y zeolites were more important,which enhanced the adsorption capacity and accessibility of substrate molecules,thus facilitating the entire catalytic cracking process.This method could be used to detect the location of rare earth elements in Y zeolites to understand the mechanism of rare earth catalysis.

Organophosphorus pesticides(OPs)are widely used in global agriculture,and pose a serious threat to ecological environment and human health due to their high environmental persistence and biological toxicity.Colorimetric sensing strategies based on the inhibition of acetylcholinesterase(AChE)have become an important method for detecting OPs because of their simplicity and high specificity.However,the sensitivity is limited by the insufficient catalytic efficiency of traditional nanozymes.In this study,a one-step solvothermal method was used to synthesize polyoxometalate nanoribbons(POM)loaded with gold nanoparticles(Au NPs),named Au-POM.Experimental results showed that Au-POM could catalyze the decomposition of H2O2 in an acidic environment(pH 4.0),demonstrating typical peroxidase-like activity.Based on this,an AChE,choline oxidase(ChOx)and Au-POM nano enzyme cascade catalytic system was constructed.In this system,AChE specifically catalyzed the hydrolysis of acetylcholine(ACh)to choline,and then ChOx mediated the oxidation of choline to produce H2O2.During this process,Au-POM acted as a peroxidase-like enzyme to catalyze the decomposition of H2O2 to generate reactive oxygen species,triggering a specific oxidation reaction of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine(TMB)into oxidized form.When the OP pesticide ethoprophos(EP)was present,it inhibited the activity of AChE and blocked the generation of ACh and H2O2,indirectly inhibiting the oxidation of TMB.The color and absorbance of the solution changed in a concentration-dependent manner.The detection limit of this method for EP was 1.05 μmol/L,and the linear response range was 20-180 μmol/L(R2=0.998).This method was applied to detection of environmental water samples and coriander samples with satisfactory results,providing a reliable technical platform for monitoring of OPs in environment and food.

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