The effects of umbilical cord-derived macrophage exosomes loaded with cisplatin on the growth and drug resistance of ovarian cancer cells.

Objective: To assess the feasibility of an exosome-based drug delivery platform for the potent chemotherapeutic agent cisplatin to treat ovarian cancer.Significance: Exosomes have recently been used as drug delivery vehicles because of their natural advantages. Platinum-resistant forms of ovarian cancer require novel drug delivery methods to improve patient outcomes.Methods: We developed and compared different methods of loading exosomes released by mononuclear M1 and M2 macrophages from umbilical cord blood with cisplatin. We characterized the morphology, drug capacity, method of cellular entry, and antitumor efficacy of the exosomes in vitro.Results: Disruption of the exosomal membrane by sonication facilitated a high loading efficiency. Importantly, incorporation of cisplatin into umbilical cord blood-derived M1 macrophage exosomes increased its cytotoxicity 3.3× in drug-resistant A2780/DDP cells and 1.4× in drug-sensitive A2780 cells over chemotherapy alone. Loading of cisplatin into M2 exosomes increased its cytotoxicity by nearly 1.7× in drug-resistant A2780/DDP cells and 1.4× in drug-sensitive A2780 cells.Conclusions: We conclude that cisplatin-loaded M1 exosomes are potentially powerful new tools for the delivery of chemotherapeutics to treat cancers regardless of drug resistance.

[Effect of LINE1-ORF1p overexpression on the proliferation of nephroblastoma WT_CLS1 cells].

OBJECTIVE: To prepare the LINE1-ORF1p polyclonal antibody, and to study the effect of LINE1-ORF1p on the proliferation of nephroblastoma WT_CLS1 cells. METHODS: A genetic engineering method was used to achieve prokaryotic expression of LINE1-ORF1p, and rabbits were immunized with LINE1-ORF1p to prepare polyclonal antibody. Indirect ELISA was used to evaluate antibody titer, and Western blot and immunohistochemistry were used to evaluate the specific ability of antibody to recognize LINE1-ORF1p. The eukaryotic expression vector pEGFP-N1-LINE1-ORF1 was constructed and used to transfect WT_CLS1 cells. Western blot and qRT-PCR were used to measure the protein and mRNA expression of LINE1-ORF1, respectively, and cell proliferation assay and colony-forming assay were used to evaluate the effect of LINE1-ORF1p on the proliferation of WT_CLS1 cells and the formation of tumor cell clone. RESULTS: The LINE1-ORF1p antibody prepared had a titer of >1:16 000 and could specifically recognize LINE1-ORF1p in cells and tumor tissue. WT_CLS1 cells transfected with pEGFP-N1-LINE1-ORF1 had significant increases in the mRNA and protein expression of LINE1-ORF1 and significantly enhanced cell proliferation ability and colony formation ability (P<0.05). CONCLUSIONS: LINE1-ORF1p can promote the growth of nephroblastoma cells and the formation of tumor cell clone, and may be involved in the pathogenesis of nephroblastoma.

The glucagon like peptide 1 analogue, exendin-4, attenuates oxidative stress-induced retinal cell death in early diabetic rats through promoting Sirt1 and Sirt3 expression.

This study was aimed to further investigate the possible mechanisms by which the glucagon like peptide 1 analogue, exendin-4 (EX4), protects rat retinal cells at the early stage of diabetes. EX4 was injected intravitreally into normal and early-stage streptozotocin-diabetic rats. Cell death, reactive oxygen species (ROS), and electroretinogram (ERG) were measured. Sirtuin (Sirt) mRNA and protein were analyzed. In retinas of diabetic rats 1 month after diabetes onset, cell death and ROS level increased significantly, and the b-wave amplitudes and OPs were significantly reduced. Four days after intravitreal EX4 treatment, retinal cell death and ROS level in retinas reduced significantly, and visual function was recovered. In the retinas of early-stage diabetic rats, the expressions of Sirt1 and Sirt3 were also found to be significantly decreased, and both were back to normal levels after intravitreal injection of EX4. In R28 cells, hydrogen peroxide (H2O2) treatment increased ROS and cell death and decreased Sirt1 and Sirt3. With the addition of EX4 into the culture system, the expressions of Sirt1 and Sirt3 were increased, and the H2O2-induced ROS and cell death were significantly reduced. These results confirm a mechanism for EX4 to protect retinal cells from diabetic damage and oxidative injury. EX4 reduces retinal cell death and ROS generation by upregulating Sirt1 and Sirt3 expressions in the retina of early-stage diabetic rats as well as in H2O2-treated R28 cells.

A label-free DNAzyme-cleaving fluorescence method for the determination of trace Pb(2+) based on catalysis of AuPd nanoalloy on the reduction of rhodamine 6G.

The substrate chain of double-stranded DNA (dsDNA) could be specifically cleaved by Pb(2+) to release single-stranded DNA (ssDNA) that adsorbs onto the AuPd nanoalloy (AuPdNP) to form a stable AuPdNP-ssDNA complex, but the dsDNA can not protect AuPdNPs in large AuPdNP aggregates (AuPdNPA) under the action of NaCl. AuPdNP-ssDNA and large AuPdNPA could be separated by centrifugation. On increasing the concentration of Pb(2+) , the amount of released ssDNA increased; AuPdNP-ssDNA increased in the centrifugation solution exhibiting a catalytic effect on the slow reaction of rhodamine 6G (Rh6G) and NaH2 PO2 , which led to fluorescence quenching at 552 nm. The decrease in fluorescence intensity (ΔF) was linear to the concentration of Pb(2+) within the range 0.33-8.00 nmol/L, with a detection limit of 0.21 nmol/L. The proposed method was applied to detect Pb(2+) in water samples, with satisfactory results.

A nanogold resonance Rayleigh scattering method for determination of trace As based on the hydride nanoreaction.

In H2 SO4 solution, As(III) was reduced to arsine (AsH3 ) by NaBH4 , and was absorbed in HAuCl4 solution to form nanogold particles (NGs) that exhibited a resonance Rayleigh scattering (RRS) effect at 370 nm. Under the selected conditions, when the As(III) concentration increased the RRS peak also increased due to the formation of more NGs. There was a linear correlation between RRS intensity and As(III) concentration in the range 6-1000 ng/mL, with a detection limit of 3 ng/mL. This new hydride generation-nanogold reaction RRS (HG-NG RRS) method was applied to determine trace amounts of As in milk samples, with satisfactory results.

A simple and sensitive resonance Rayleigh scattering method for determination of As(III) using aptamer-modified nanogold as a probe.

A simple and selective aptamer (ssDNA)-modified nanogold probe (AussDNA) was prepared for the determination of trace As(III) in HEPES buffer solution (pH 8.2) containing 0.05 mol/L NaCl. The method coupled the aptamer reaction of AussDNA-As(III) and the resonance Rayleigh scattering (RRS) of nanogold aggregations at 278 nm. When the As(III) concentration increased, the RRS intensity at 278 nm increased to form more nanogold aggregation and a stable As(III)-ssDNA complex. Under selected conditions, the increased RRS intensity (ΔI) was linear to the concentration of As(III) in the range 3.8-230.4 ng/mL, with a detection limit of 1.9 ng/mL. This RRS method was applied to detect As(III) in water samples, with simplicity, sensitivity and selectivity.

A new method of alkalinity remediation for Cd-contaminated groundwater by PAAS-modified MgCO3/Mg(OH)2 colloid.

Mg(OH)2 dissolves slowly and can provide a long-term source of alkalinity, thus a promising alternative reagent for the in situ remediation of heavy metal polluted groundwater. Unfortunately, it exhibits a relatively poor stabilization effect on heavy metal Cd due to the higher solubility of the resulting stabilized product, Cd(OH)2. To overcome this limitation, we investigated the use of MgCO3/Mg(OH)2 colloid modified by sodium polyacrylate (PAAS) to remove Cd from groundwater. Through ultrasonic dispersion, the molecular chains of PAAS are broken, causing a transformation from flocculation to surface modification, resulting in the production of a stable colloid. The colloidal particles of MgCO3/Mg(OH)2 have a smaller size and a negatively charged surface, which significantly enhances their migration ability in aquifers. The combination of MgCO3 and Mg(OH)2 provides a complementary effect, where MgCO3 effectively precipitates Cd in the aquifer while Mg(OH)2 maintains the required pH level for stabilization. The optimal compounding ratio of MgCO3 to Mg(OH)2 for achieving the best stabilization effect on Cd is found to be 1:1. Column experiments demonstrate that the injection of MgCO3/Mg(OH)2 colloid substantially enhances Cd stability, reducing the exchangeable fraction of Cd in aquifer media from 88.61% to a range of 22.50-34.38%. Based on these results, the MgCO3/Mg(OH)2 colloid shows great potential as a reactive medium for remediating Cd-contaminated groundwater.

Fructose-1,6-bisphosphatase deficiency: estimation of prevalence in the Chinese population and analysis of genotype-phenotype association.

Objective: Fructose-1,6-bisphosphatase deficiency (FBP1D) is a rare inborn error due to mutations in the FBP1 gene. The genetic spectrum of FBP1D in China is unknown, also nonspecific manifestations confuse disease diagnosis. We systematically estimated the FBP1D prevalence in Chinese and explored genotype-phenotype association. Methods: We collected 101 FBP1 variants from our cohort and public resources, and manually curated pathogenicity of these variants. Ninety-seven pathogenic or likely pathogenic variants were used in our cohort to estimate Chinese FBP1D prevalence by three methods: 1) carrier frequency, 2) permutation and combination, 3) Bayesian framework. Allele frequencies (AFs) of these variants in our cohort, China Metabolic Analytics Project (ChinaMAP) and gnomAD were compared to reveal the different hotspots in Chinese and other populations. Clinical and genetic information of 122 FBP1D patients from our cohort and published literature were collected to analyze the genotype-phenotypes association. Phenotypes of 68 hereditary fructose intolerance (HFI) patients from our previous study were used to compare the phenotypic differences between these two fructose metabolism diseases. Results: The estimated Chinese FBP1D prevalence was 1/1,310,034. In the Chinese population, c.490G>A and c.355G>A had significantly higher AFs than in the non-Finland European population, and c.841G>A had significantly lower AF value than in the South Asian population (all p values < 0.05). The genotype-phenotype association analyses showed that patients carrying homozygous c.841G>A were more likely to present increased urinary glycerol, carrying two CNVs (especially homozygous exon1 deletion) were often with hepatic steatosis, carrying compound heterozygous variants were usually with lethargy, and carrying homozygous variants were usually with ketosis and hepatic steatosis (all p values < 0.05). By comparing to phenotypes of HFI patients, FBP1D patients were more likely to present hypoglycemia, metabolic acidosis, and seizures (all p-value < 0.05). Conclusion: The prevalence of FBP1D in the Chinese population is extremely low. Genetic sequencing could effectively help to diagnose FBP1D.

A Boundary-Enhanced Decouple Fusion Segmentation Network for Diagnosis of Adenomatous Polyps.

Adenomatous polyps, a common premalignant lesion, are often classified into villous adenoma (VA) and tubular adenoma (TA). VA has a higher risk of malignancy, whereas TA typically grows slowly and has a lower likelihood of cancerous transformation. Accurate classification is essential for tailored treatment. In this study, we develop a deep learning-based approach for the localization and classification of adenomatous polyps using endoscopic images. Specifically, a pre-trained EGE-UNet is first adopted to extract regions of interest from original images. Multi-level feature maps are then extracted by the feature extraction pipeline (FEP). The deep-level features are fed into the Pyramid Pooling Module (PPM) to capture global contextual information, and the squeeze body edge (SBE) module is then used to decouple the body and edge parts of features, enabling separate analysis of their distinct characteristics. The Group Aggregation Bridge (GAB) and Boundary Enhancement Module (BEM) are then applied to enhance the body features and edge features, respectively, emphasizing their structural and morphological characteristics. By combining the features of the body and edge parts, the final output can be obtained. Experiments show the proposed method achieved promising results on two private datasets. For adenoma vs. non-adenoma classification, It achieved a mIoU of 91.41%, mPA of 96.33%, mHD of 11.63, and mASD of 2.33. For adenoma subclassification (non-adenomas vs. villous adenomas vs. tubular adenomas), it achieved a mIoU of 91.21%, mPA of 94.83%, mHD of 13.75, and mASD of 2.56. These results demonstrate the potential of our approach for precise adenomatous polyp classification.

Site-Directed Mutagenesis of VvCYP76F14 (Cytochrome P450) Unveils Its Potential for Selection in Wine Grape Varieties Linked to the Development of Wine Bouquet.

Bouquet is a fascinating wine characteristic that serves as an indicator of wine quality, developing during the aging process. The multifunctional monoterpenol oxidase VvCYP76F14 in wine grapes sequentially catalyzes three reactions to produce (E)-8-carboxylinalool, a crucial precursor for wine bouquet. Previous studies indicated that the activity of VvCYP76F14 derived from different wine grape varieties did not correlate with the amino acid sequence differences. In this study, 54 wine grape varieties were categorized into neutral, aromatic, and full-bodied types based on the sequence differences of VvCYP76F14, closely correlated with the content of wine lactone precursors. Computer modeling and molecular docking analysis of the full-bodied CYP76F14 revealed 17, 19, and 18 amino acid residues in the VvCYP76F14-linalool, VvCYP76F14-(E)-8-hydroxylinalool, and VvCYP76F14-(E)-8-oxolinalool complexes, respectively. Site-directed mutagenesis and in vitro enzyme activity analysis confirmed the substitutions of the key amino acid residues in neutral and aromatic varieties. Notably, the D299 mutation of VvCYP76F14 resulted in the complete loss of (E)-8-oxolinalool and (E)-8-carboxylinalool activities, aligning with the undetectable levels of (E)-8-oxolinalool and (E)-8-carboxylinalool in "Yantai 2-3-37", which harbors the D299T substitution. Favorably, VvCYP76F14 could serve as a cost-effective fingerprint marker for screening superior hybrid offspring with the desired levels of wine lactone precursors.

Association of family income to poverty ratio and vibration-controlled transient elastography quantified degree of hepatic steatosis in U.S. adolescents.

Introduction: Inequality in socioeconomic status plays an important role in the prevalence of metabolic diseases in adolescents. The purpose of this study was to explore the association between family income and the degree of hepatic steatosis quantified by vibration-controlled transient elastography (VCTE) among U.S. adolescents. Methods: This cross-sectional study included two cycles of the National Health and Nutrition Examination Survey (NHANES) 2017-2020. Multivariate linear regression and smoothing curve fitting were used to investigate the linear and nonlinear relationship between PIR and hepatic steatosis, respectively. Subgroup analysis and interaction tests were used to test whether this relationship was stable across groups. Results: Of the 1,574 adolescent participants, 456 lived in poor households and 307 lived in wealthy households. After adjusting for all covariates, PIR (Ratio of family income to poverty) was significantly negatively associated with the degree of hepatic steatosis [-4.78 (-7.39, -2.17)], and this remained stable after converting PIR to a categorical variable. In addition, this significant negative association was more pronounced in women [-7.62 (-11.38, -3.87)], non-Hispanic blacks [-7.19 (-14.43, 0.06)], Mexican Americans [-6.80 (-13.63, 0.03)], and participants with BMI >30 cm2 [-10.83 (-19.70, -1.96)]. Conclusions: PIR was significantly and negatively associated with the degree of hepatic steatosis in US adolescents. Additional prospective studies are needed to confirm our findings.

Association between urine caffeine metabolites and bone mineral density: A population-based study.

The association between coffee intake and bone mineral density (BMD) remains a subject of debate in epidemiological research. Furthermore, the potential relationship between BMD and urine caffeine or caffeine metabolites has not yet been explored. Therefore, the present study aimed to investigate the possible association between BMD and urine caffeine and its metabolites in U.S. adults. We employed multivariate linear and logistic regression models to analyze the relationship between urine caffeine and caffeine metabolites and lumbar BMD using data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014. Additionally, fitted smoothing curves and generalized additive models were used. After adjusting for several factors, we found no significant association between urine caffeine and its metabolites and BMD. However, subgroup analyses stratified by gender and ethnicity showed that the relationship between urine caffeine and its metabolites and lumbar BMD remained consistent. Our investigation revealed that the inflection points for the U-shaped relationship between urinary theophylline and paraxanthine and BMD were observed at levels of 0.006 mmol/L for theophylline and 0.052 mmol/L for paraxanthine. In this cross-sectional study, we found no significant correlation between urine caffeine and its metabolites and BMD. However, more research is required to confirm our findings, as well as to investigate the underlying mechanisms.

A prognostic nomogram and risk classification system of elderly patients with extraosseous plasmacytoma: a SEER database analysis.

BACKGROUND: The survival trends and prognostic factors of patients with extraosseous plasmacytoma (EOP) or extramedullary plasmacytoma (EMP) have not been reported in recent years. The objective of this study was to develop a novel nomogram and risk stratification system for predicting the overall survival (OS) of elderly patients with EOP based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: The demographic characteristics of 900 patients aged 60 years and above, diagnosed with EOP between 2000 and 2019, were extracted from the SEER database. The patient population was randomly divided into a training cohort and an internal validation cohort in a ratio of 7:3. Univariate and multivariate Cox regression analyses were conducted to identify independent predictors of prognosis in elderly EOP patients, followed by developing a nomogram for prognostic assessment. The performance of the model was evaluated through receiver-operating characteristic (ROC) curves, C-index, calibration curves for calibration accuracy assessment, and decision curve analysis (DCA) to assess its clinical utility. All elderly EOP patients were stratified into three risk subgroups by cutoff value utilizing X-tile software based on their total OS scores for comparative analysis purposes. Kaplan-Meier (K-M) survival curve analysis was employed to validate any observed differences in OS among these three risk groups. RESULTS: Six factors including age, year of diagnosis, marital status, primary site, surgery, and prior tumor history were identified to be independently predictive of the OS of elderly patients with EOP, and these predictors were included in the construction of the nomogram. The 1-, 3-, and 5-year area under the curves (AUCs) for OS were 0.717, 0.754, and 0.734 in the training cohort and 0.740, 0.730, and 0.765 in the validation cohort, respectively. The C-index values in the two cohorts were 0.695 and 0.690. The calibration curves and DCA exhibit commendable consistency and validity, respectively, thereby demonstrating their robust performance. The training set was stratified into low-, medium-, and high-risk subgroups based on the optimal cutoff points (167.8 and 264.8) identified. The K-M curve and cumulative risk curve exhibited statistically significant disparities in survival rates among the groups. CONCLUSIONS: We developed a nomogram and risk classification system, which can serve as an intuitive and effective tool for clinicians to enhance the prediction of OS in elderly EOP patients, thereby facilitating the formulation of more rational and personalized treatment strategies.

Global trends in research on oxidative stress related to heart failure from 2012 to 2021: a bibliometric analysis and suggestion to researchers.

Background: Oxidative stress leads to an increase in reactive oxygen in the body. During heart failure (HF), when the body's antioxidant defense system fails to remove excessive reactive oxygen species, myocardial cells will be damaged or even die. Over the past ten years, the number of research publications on oxidative stress related to HF has increased. Methods: We searched publications published in 2012-2021 and the Web of Science Core Collection (WoSCC) recording information. Based on the VOSviewer and CiteSpace, we conducted a bibliometric analysis of the overall distribution of journals, keywords, authors, major countries, annual output, active institutions, and cocited literature. The Global Citation Score (GCS) was used to evaluate the impact and quality of highly cited papers. Results: We retrieved 5,616 articles and reviews. Over the past ten years, the number of annual publications on oxidative stress related to HF has increased. USA has published the largest number of articles and obtained the highest number of citations (NC) and H-index. The University of California and PLoS One are the most productive affiliations and journals in terms of publications on oxidative stress related to HF. The GCS of articles written by Paulus WJ in 2013 was 1,632, which was the top ranking. The most frequent keywords are "oxidative stress", "heart failure", "inflammation", "dysfunction" and "apoptosis". The top three authors are Kang Yuming, Ren Jun and Okoshi Katashi. "Impact", "induced myocardial infarction", "cardiovascular outcome", "empagliflozin", "sglt2 inhibitor", "protect", and "Na+/H+ exchanger" have become popular research topics. Conclusions: Our research shows the research focus and development trends of oxidative stress related to HF in the past decade. Understanding the most important indicators of oxidative stress related to HF and the hot spots in the field of oxidative stress research related to HF can assist scholars, countries and policy-makers in the field in better understanding oxidative stress related to HF and can also lead to better decisions in oxidative stress treatment.

The haplotype-resolved T2T genome of teinturier cultivar Yan73 reveals the genetic basis of anthocyanin biosynthesis in grapes.

Teinturier grapes are characterized by the typical accumulation of anthocyanins in grape skin, flesh, and vegetative tissues, endowing them with high utility value in red wine blending and nutrient-enriched foods developing. However, due to the lack of genome information, the mechanism involved in regulating teinturier grape coloring has not yet been elucidated and their genetic utilization research is still insufficient. Here, the cultivar 'Yan73' was used for assembling the telomere-to-telomere (T2T) genome of teinturier grapes by combining the High Fidelity (HiFi)， Hi-C and ultralong Oxford Nanopore Technologies (ONT) reads. Two haplotype genomes were assembled, at the sizes of 501.68 Mb and 493.38 Mb, respectively. In the haplotype 1 genome, the transposable elements (TEs) contained 32.77% of long terminal repeats (LTRs), while in the haplotype 2 genome, 31.53% of LTRs were detected in TEs. Furthermore, obvious inversions were identified in chromosome 18 between the two haplotypes. Transcriptome profiling suggested that the gene expression patterns in 'Cabernet Sauvignon' and 'Yan73' were diverse depending on tissues, developmental stages, and varieties. The transcription program of genes in the anthocyanins biosynthesis pathway between the two cultivars exhibited high similarity in different tissues and developmental stages, whereas the expression levels of numerous genes showed significant differences. Compared with other genes, the expression levels of VvMYBA1 and VvUFGT4 in all samples, VvCHS2 except in young shoots and VvPAL9 except in the E-L23 stage of 'Yan73' were higher than those of 'Cabernet Sauvignon'. Further sequence alignments revealed potential variant gene loci and structure variations of anthocyanins biosynthesis related genes and a 816 bp sequence insertion was found in the promoter of VvMYBA1 of 'Yan73' haplotype 2 genome. The 'Yan73' T2T genome assembly and comparative analysis provided valuable foundations for further revealing the coloring mechanism of teinturier grapes and the genetic improvement of grape coloring traits.

Clinical features of infants with SARS-CoV-2 infection: a systematic review and meta-analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to coronavirus disease 2019 (COVID-19) and is a public health problem. This meta-analysis reviewed the clinical features of SARS-CoV-2 infection among infants. METHODS: PubMed, Scopus, Web of Science, and the Cochrane Library were searched for studies on clinical features of infants with SARS-CoV-2 published before May 1, 2022. Two authors screened and extracted data on the number of infants with SARS-CoV-2 infection, clinical features, and number of clinical features. The proportion of asymptomatic infection, mild symptoms, moderate symptoms, severe symptoms, and the clinical features were analyzed. RESULTS: Forty-four studies with 6,304 infants with SARS-CoV-2 infections were included in this study. The proportion of asymptomatic infection was 20% (95% CI: 11-28%, I2=97%, P<0.01) in infants with SARS-CoV-2 infections. The proportion of infants with mild, moderate, and severe symptoms was 48% (95% CI: 30-65%, I2=96%, P<0.01), 27% (95% CI: 10-44%, I2=93%, P<0.01), and 8% (95% CI: 0-16%, I2=90%, P<0.01), respectively. Notably, the most common clinical features of infants with SARS-CoV-2 infection were fever (64%), cough (34%), and nasal symptoms (31%). CONCLUSIONS: This meta-analysis found that 20% of infants with SARS-CoV-2 infections were asymptomatic, while most infants with COVID-19 presented with mild symptoms.

Application Effect of Whole-Process Seamless Nursing Model Based on Smart Healthcare Mode in Perioperative Period of Patients Undergoing Hematoma Removal.

OBJECTIVE: To explore the application effect of a whole-process seamless nursing model based on the smart healthcare mode in the perioperative period of patients undergoing hematoma removal. METHODS: In this retrospective study, 50 patients with hematoma removal admitted to our hospital from August 2018 to August 2019 were included as the control group (CG), while 50 patients with hematoma removal admitted to our hospital from September 2019 to September 2020 were included as the experimental group (EG). During the period of hematoma removal, CG received routine perioperative nursing, while EG received the whole-process seamless nursing model based on the smart healthcare mode. The perioperative indexes, hemodynamic indexes, and the incidence of postoperative complications were compared between the two groups, and the incidence of nursing staff's work omissions in different periods was analyzed. RESULTS: Notable differences were observed in surgical time, intraoperative blood loss, hematoma clearance rates, length of ICU stay, hospitalization time, removal time of ventricular drainage tube, and cerebral edema volume at 1 week after surgery between EG and CG (P < 0.05). Compared with CG, EG achieved obviously better hemodynamic indexes (P < 0.001) and a lower incidence of bedsore, muscle atrophy, and eating/swallowing disorders (P < 0.05). During the implementation of smart healthcare, the incidence of nursing staff's work omissions was remarkably reduced (P < 0.05). CONCLUSION: Under the smart healthcare, the incidence of nursing staff's work omissions is lower, and the effect of the whole-process seamless nursing is better, which can optimize the perioperative indexes of patients, stabilize the postoperative hemodynamics, and reduce the incidence of complications. Therefore, the whole-process seamless nursing model based on the smart healthcare mode has promotion value in clinic.

Diagnostic utility of rapid sequencing in critically ill infants: a systematic review and meta-analysis.

BACKGROUND: Genetic disorders are a major cause of death in critically ill infants. Several studies have assessed the diagnostic yield of rapid genomic sequencing in critically ill infants. This meta-analysis aimed to summarize the diagnostic utility of rapid genomic sequencing in critically ill infants. METHODS: PubMed, Scopus, Web of Science, and Cochrane Library, were searched before 1 July 2022. Studies reported diagnostic rate of rapid genomic sequencing in critically ill infants were selected. Two authors screened and extracted data regarding the method of genetic test, total number of patients, and number of diagnosed patients. RESULTS: Twenty-three studies, comprising 1567 critically ill infants were included in the meta-analysis. In the overall analysis, the pooled diagnostic utility of rapid genomic sequencing was 0.42 (95% CI: 0.37-0.49, I2 = 79%, P < 0.1). Moreover, the pooled diagnostic rates of rapid whole-exome and rapid whole-genome sequencing were 0.50 (95% CI: 0.41-0.61; I2 = 74%; P < 0.01) and 0.37 (95% CI: 0.30-0.46; I2 = 77%; P < 0.01), respectively. Sensitive analysis showed that the results were stable in the overall analysis. Additionally, publication bias was not observed in the overall analysis. CONCLUSIONS: This meta-analysis proved that rapid genomic sequencing has a good diagnostic utility for critically ill infants.

Estimation of hereditary fructose intolerance prevalence in the Chinese population.

BACKGROUND: Hereditary fructose intolerance (HFI) caused by aldolase B reduction or deficiency that results in fructose metabolism disorder. The disease prevalence in the Chinese population is unknown, which impedes the formulation of HFI screening and diagnosis strategies. MATERIALS AND METHODS: By searching a local cohort (Chinese Children's Rare Disease Genetic Testing Clinical Collaboration System, CCGT) and public databases (ClinVar and Human Gene Mutation Database) and reviewing HFI-related literature, we manually curated ALDOB pathogenic or likely pathogenic (P/LP) variants according to ACMG guidelines. Allele frequency (AF) information from the local database CCGT and the public databases HuaBiao and gnomAD for ALDOB P/LP variants was used to estimate and the HFI prevalence in the Chinese population and other populations by the Bayesian framework. We collected the genotype and clinical characteristics of HFI patients from the CCGT database and published literature to study genotype-phenotype relationships. RESULT: In total, 81 variants of ALDOB were curated as P/LP. The estimated Chinese HFI prevalence was approximately 1/504,678, which was much lower than that for non-Finland European (1/23,147), Finnish in Finland (1/55,539), admixed American (1/132,801) and Ashkenazi Jewish (1/263,150) populations. By analyzing the genetic characteristics of ALDOB in the Chinese population, two variants (A338V, A338G) had significantly higher AFs in the Chinese population than in the non-Finland European population from gnomAD (all P values < 0.05). Five variants (A150P, A175D, N335K, R60*, R304Q) had significantly lower AFs (all P values < 0.1). The genotype-phenotype association analyses were based on 68 reported HFI patients from a literature review and the CCGT database. The results showed that patients carrying homozygous variant sites (especially A150P) were more likely to present nausea, and patients carrying two missense variant sites were more likely to present aversion to sweets and fruit (all P values < 0.05). Our research reveals that some gastrointestinal symptoms seem to be associated with certain genotypes. CONCLUSION: The prevalence of HFI in the Chinese population is extremely low, and there is no need to add HFI testing to the current newborn screening programs if medical costs are considered. A genetic testing strategy is suggested for early diagnosis of HFI.

Paeoniflorin ameliorates chronic stress-induced depression-like behavior in mice model by affecting ERK1/2 pathway.

Depression is a mental and emotional disorder that has made an opening great burden to the society. Paeoniflorin showed remarkable antidepressant-like effects in multiple animal models with depressive disorders. However, the molecule of paeoniflorin on depression is less studied. This study aims to explore the effect and the molecular mechanism of paeoniflorin on depression in a chronic restraint stress (CRS) mice model. CRS model of C57BL/6 J mice was set up. Sucrose preference test (SPT), tail suspension test (TST), open field test (OFT) and forced swimming test (FST) were used to assess depression symptoms. Immunofluorescence staining, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were implemented to detect the expression changes of the proteins involved in extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Results showed that paeoniflorin treatment decreased the degree of depression in the CRS mice. Further analysis showed that the expression of ERK1/2 proteins was significantly downregulated, while paeoniflorin could elevate the expression of ERK1/2 proteins in CRS mice. Finally, it showed that inhibiting signaling ERK1/2 pathway could aggravate the depressive behavior when treatment with ERK-specific inhibitor U0126, while the condition could be partially relieved when treated with paeoniflorin. In conclusion, the present study demonstrated that paeoniflorin attenuated chronic stress-induced depression-like behavior in mice by affecting the ERK1/2 pathway. These findings provided the basis for the molecular mechanism of paeoniflorin on the effect of depression, which support paeoniflorin might act as an important drug in the treatment of depression.