Association between CYP2C9 and VKORC1 genetic polymorphisms and efficacy and safety of warfarin in Chinese patients.

OBJECTIVES: Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy. METHODS AND RESULTS: Univariate analyses unveiled significant associations between two specific single nucleotide polymorphisms rs1057910 in CYP2C9 and rs9923231 in VKORC1 and stable warfarin dosage ( P  < 0.001). Further, employing multivariate logistic regression analysis adjusted for age, sex and height, the investigation revealed that patients harboring at least one variant allele in CYP2C9 exhibited a heightened risk of bleeding events compared to those with the wild-type genotype (odds ratio = 2.16, P  = 0.04). Moreover, a meta-analysis conducted to consolidate findings confirmed the associations of both CYP2C9 (rs1057910) and VKORC1 (rs9923231) with stable warfarin dosage. Notably, CYP2C9 variant genotypes were significantly linked to an increased risk of hemorrhagic complications ( P  < 0.00001), VKORC1 did not demonstrate a similar association. CONCLUSION: The associations found between specific genetic variants and both stable warfarin dosage and bleeding risk might be the potential significance of gene detection in optimizing warfarin therapy for improving patient efficacy and safety.

An integrated analysis identifies six molecular subtypes of pancreatic ductal adenocarcinoma revealing cellular and molecular landscape.

Pancreatic ductal adenocarcinoma (PDA) has been found to have a high mortality rate. Despite continuous efforts, current histopathological classification is insufficient to guide individualized therapies of PDA. We first define the molecular subtypes of PDA (MSOP) based on a meta-cohort of 845 samples from 11 PDA datasets. We then performed functional analyses involving immunity, fibrosis and metabolism. We recognized six molecular subtypes with different survival statistics and molecular composition. The squamous basal-like (SBL) subtype had a poor prognosis and high infiltration of ENO1+ (Enolase 1)/ADM+ (Adrenomedullin) cancer-associated fibroblasts (CAFs). The immune mesenchymal-like (IML) subtype and the normal mesenchymal-like (NML) subtype were characterized by genes associated with extracellular matrix (ECM) activities and immune responses, having favorable prognoses. IML was featured by elevated exhausted immune signaling and inflammatory CAFs infiltration, whereas NML was featured with myofibroblastic CAFs infiltration. The exocrine-like (EL) subtype was high in exocrine signals, while the pure classical-like (PCL) subtype lacked immunocytes infiltration. The quiescent-like (QL) subtype had diminished metabolic signaling and high infiltration of NK cells. SBL, IML and NML were enriched in innate anti-PD-1 resistance signatures. In sum, this MSOP depicts a vivid cell-to-molecular atlas of the tumor microenvironment of PDA and might facilitate to design a precise combination of therapies that target immunity, metabolism and stroma.

Tissue-resident innate lymphoid cells in asthma.

Asthma is a chronic airway inflammatory disease whose global incidence increases annually. The role of innate lymphoid cells (ILCs) is a crucial aspect of asthma research with respect to different endotypes of asthma. Based on its pathological and inflammatory features, asthma is divided into type 2 high and type 2 low endotypes. Type-2 high asthma is distinguished by the activation of type 2 immune cells, including T helper 2 (Th2) cells and ILC2s; the production of cytokines interleukin (IL)-4, IL-5 and IL-13; eosinophilic aggregation; and bronchial hyper-responsiveness. Type-2 low asthma represents a variety of endotypes other than type 2 high endotype such as the IL-1ß/ILC3/neutrophil endotype and a paucigranulocytic asthma, which may be insensitive to corticosteroid treatment and/or associated with obesity. The complexity of asthma is due to the involvement of multiple cell types, including tissue-resident ILCs and other innate immune cells including bronchial epithelial cells, dendritic cells, macrophages and eosinophils, which provide immediate defence against viruses, pathogens and allergens. On this basis, innate immune cells and adaptive immune cells combine to induce the pathological condition of asthma. In addition, the plasticity of ILCs increases the heterogeneity of asthma. This review focuses on the phenotypes of tissue-resident ILCs and their roles in the different endotypes of asthma, as well as the mechanisms of tissue-resident ILCs and other immune cells. Based on the phenotypes, roles and mechanisms of immune cells, the therapeutic strategies for asthma are reviewed.

Decrease of lncRNA MEG3 in Acute Myeloid Leukemia Affected the Expression of p53 and MDM2.

BACKGROUND: The aim was to determine the clinical role of long non coding maternally expressed gene 3 (lncRNA MEG3) in adult acute myeloid leukemia (AML). METHODS: The expression levels of lncRNA MEG3 in bone marrow of AML patients and healthy donors were determined by qPCR. The correlation between expression levels of lncRNA MEG3 and clinical features was also analyzed. MTT assay and flow-cytometric assay were employed to determine the role of lncRNA MEG3 on the cell viability and apoptosis of AML cell lines. Expression levels of caspase-9, Bcl-2, MDM2, and p53 in those cells were determined by western blot. RESULTS: The expression levels of lncRNA MEG3 was significantly down-regulated in AML patients. Expression levels of lncRNA MEG3 were positively correlated with overall survival of patients. Up-regulation of lncRNA MEG3 could not only inhibit the cell growth and promoted apoptosis, but also increased the expression of caspase-9 and p53 and decreased the expression of Bcl-2 and MDM2. CONCLUSIONS: These results suggest that down-regulation of lncRNA MEG3 in AML patients might promote tumor progression and affect the p53-MDM2 pathway.

A Seawater Salinity Sensor Based on Optimized Long Period Fiber Grating in the Dispersion Turning Point.

Variations of seawater salinity often cause ocean internal waves, water masses and stratification, which affect the stability of the ocean environment. Therefore, the study of seawater salinity is significant for the prediction of changes in the ocean environment. However, existing methods for measuring seawater salinity generally have the disadvantages of low sensitivity and low accuracy. In this work, we proposed a seawater salinity sensor based on long period fiber grating (LPFG) in the dispersion turning point (DTP), which has demonstrated the possibility to fabricate LPFG with a shorter grating period by CO2 laser in a thin single mode fiber (SMF) of 80 µm cladding diameter without etching. For obtaining higher sensitivity that could meet the measurement requirement in practice, the proposed sensor was optimized by combining etching cladding and DTP. After the LPFG working near DTP was fabricated by a CO2 laser, the cladding diameter was reduced to 57.14 µm for making cladding mode LP1,7 work near DTP by hydrofluoric acid (HF) solutions. The experimental results have demonstrated that a sensitivity of 0.571 nm/‱ can be achieved when the salinity increases from 5.001‱ to 39.996‱, and the sensor shows good repeatability and stability. Based on its excellent performance, the optimized LPFG is a prospective sensor to monitor seawater salinity in real time. Meanwhile, a low-cost way was provided to make LPFG work near DTP instead of ultraviolet exposure and femtosecond laser writing.

[Association between Gestational Diabetes Mellitus and Postpartum Depressive Episode].

Objective To explore the association between gestational diabetes mellitus (GDM) and postpartum depressive (PPD) episode and the influencing factors of PPD episode. Methods The clinical data of pregnant women who filed in the Department of Obstetrics,Peking Union Medical College Hospital from March 1,2020 to February 28,2021 were collected.Oral glucose tolerance test (OGTT,75 g) and determination of glycosylated hemoglobin (HbA1c) were carried out in the second trimester,and fasting blood glucose and glycosylated albumin (GA) were determined in the third trimester.Mini-International Neuropsychiatric Interview (MINI,5.0 Chinese version) was used to diagnose depressive episode and anxiety disorder within (42±7) days after delivery.We analyzed the influencing factors of PPD episode by multiple Logistic regression to explore the relationship between GDM and PPD episode.Fasting glucose and GA in the third trimester,as well as the incidence of PPD episode,between women with and without GDM were compared. Results The GDM,75 g OGTT,and HbA1c in the second trimester,as well as fasting blood glucose and GA in the third trimester,showed no significant differences between the PPD group and the non-PPD group (all P>0.05).Postpartum generalized anxiety disorder (OR=4.656,95%CI=1.130-19.184, P=0.033),obsessive-compulsive disorder (OR=11.989,95%CI=1.004-143.113, P=0.049),and the history of mental disorder before pregnancy (OR=13.567,95%CI=2.191-83.991, P=0.005) were the risk factors of PPD episode.The fasting blood glucose and GA in the third trimester,the incidence of PPD episode,and the PPD episode comorbidities of generalized anxiety disorder and obsessive-compulsive disorder had no significant differences between pregnant women with and without GDM (all P>0.05).Conclusions There is no association between GDM and PPD episode under routine blood glucose management. Special attention should be paid to pregnant women with a history of mental disorder before pregnancy.

Value of detecting peri-device leak and incomplete endothelialization by cardiac CT angiography in atrial fibrillation patients post Watchman LAAC combined with radiofrequency ablation.

OBJECTIVES: To explore the value of detecting the peri-device leak (PDL) and device endothelialization after left atrial appendage closure (LAAC) by cardiac computed tomography (CT) in patients with atrial fibrillation (AF), who underwent Watchman LAAC combined with radiofrequency ablation of atrial fibrillation (AFCA). METHODS: Patients with symptomatic drug-refractory atrial fibrillation at high risk of stroke (CHA2 DS2 -VASc Score ≥ 2), who underwent Watchman LAAC combined with AFCA in our center from March 2017 to December 2018 were enrolled. Maximum diameter of LAA orifice was determined by preoperative CCTA. A standardized view of Watchman device was obtained by postoperative CCTA multiplannar reconstruction to evaluate the PDL and device endothelialization. RESULTS: Approximately 84 patients post successful LAAC and AFCA were enrolled in this study. The satisfactory LAA occlusion rate was 100%. There was no death, bleeding, stroke, and device-related thrombus (DRT) events. At 6-month postprocedure, CCTA images evidenced complete endothelialization in 44 patients (no contrast enhancement in LAA); contrast enhancement in LAA and visible PDL in 33 patients; contrast enhancement in LAA but without PDL in seven patients (incomplete device endothelialization). Maximum diameter of LAA orifice could independently predict the occurrence of PDL (odds ratio, 1.31; 95% confidence interval, 1.11-1.55; p = .002), sensitivity was 69.7% and specificity was 80.4% with the cutoff value of maximum diameter of LAA orifice more than 28.2 mm on predicting PDL. CONCLUSIONS: CCTA is feasible to evaluate PDL and device endothelialization after LAAC. The maximum diameter of LAA orifice derived from CT can independently predict the occurrence of post-LAAC PDL.

Cytochrome P450 Enzymes and Drug Metabolism in Humans.

Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1-3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy.

[Fermentation of cellulase with multiple types of Salvia miltiorrhiza residues and other solid wastes from Chinese materia medica industrialization].

The solid wastes of Chinese materia dedica industrialization represented by Salvia miltiorrhiza residues have a strong small-molecule bio-recalcitrance in the process of high-value utilization of biotransformation. Highly tolerant strains were bred to break bio-recalcitrance of Salvia miltiorrhiza residues and produce high-value added cellulose, which has a significant significance for recycling and industrial utilization of solid waste. In this study, a strain of fungus, Penicillium expansum SZ13, was found with small-molecule antibacterial substance tanshinone contained in Salvia miltiorrhiza residues by a biological method. The optimal enzyme production process and peak period of SZ13 were determined. It was found that SZ13 could maintain peak enzyme production for 5 days by degrading residues under the conditions of temperature 35 ℃, rotation speed 180 r·min~(-1), 5% of residues addition, and 5% seed solution addition. Meanwhile, the ability of SZ13 to degrade the enzyme production of multiple types of residues was explored. The results showed a high enzyme activity and stable enzyme production of SZ13 in the process of degrading residues. SZ13 could efficiently utilize various types of Chinese medicine residues, such as Salvia miltiorrhiza residues, to realize the high-value utilization of cellulose in multiple types of residues.

Ultrasensitive Determination of Rare Modified Cytosines Based on Novel Hydrazine Labeling Reagents.

Modified cytosines are important epigenetic marks that exert critical influences in a variety of cellular processes in living organisms. However, biological functions of rare modified cytosines, especially certain functions of 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), are still unclear due to the extremely low abundance in biological samples. In this work, a series of novel hydrazine-based reagents, which held a hydrazine group as the reaction group, a hydrophobic triazine group, and two easily charged tertiary amine groups with different alkyl chains for adjusting the hydrophobicity of the labeling reagents, were first explored to label rare modified cytosines such as 5fC and 5caC. The derivatization reaction between 5fC and the labeling reagents was extremely fast, and more than 99% derivatization efficiency could be achieved only by vortexing without additional reaction time. The detection sensitivity of 5fC increased with the increase of the hydrophobicity of the labeling reagents, the best of which was dramatically enhanced by 125-fold. The limit of detection was as low as 10 amol, realizing the most sensitive genome-wide overall quantification for 5fC. Moreover, the labeling reagents were also successfully applied for the detection of 5caC with 100-fold improvement of sensitivity. With this method, we achieved the simultaneous detection of 5fC and 5caC in different mammalian tissues using only about 600 ng of genomic DNA, which was less than one-tenth of the sample consumption for other reported methods, providing an opportunity to monitor 5fC and 5caC in precious samples and biology processes that could not be investigated before.

GmBZL3 acts as a major BR signaling regulator through crosstalk with multiple pathways in Glycine max.

BACKGROUND: Brassinosteroids (BRs) play a crucial role in plant vegetative growth and reproductive development. The transcription factors BZR1 and BES1/BZR2 are well characterized as downstream regulators of the BR signaling pathway in Arabidopsis and rice. Soybean contains four BZR1-like proteins (GmBZLs), and it was reported that GmBZL2 plays a conserved role in BR signaling regulation. However, the roles of other GmBZLs have not been thoroughly studied, and the targets of GmBZLs in soybean remain unclear. RESULTS: In this study, we first characterized GmBZL3 in soybean from gene expression patterns, conserved domains in coding sequences, and genomic replication times of four GmBZL orthologous. The results indicated that GmBZL3 might play conserved roles during soybean development. The overexpression of GmBZL3P219L in the Arabidopsis BR-insensitive mutant bri1-5 partially rescued the phenotypic defects including BR-insensitivity, which provides further evidence that GmBZL3 functions are conserved between soybean and the homologous Arabidopsis genes. In addition, the identification of the GmBZL3 target genes through ChIP-seq technology revealed that BR has broad roles in soybean and regulates multiple pathways, including other hormone signaling, disease-related, and immunity response pathways. Moreover, the BR-regulated GmBZL3 target genes were further identified, and the results demonstrate that GmBZL3 is a major transcription factor responsible for BR-regulated gene expression and soybean growth. A comparison of GmBZL3 and AtBZR1/BES1 targets demonstrated that GmBZL3 might play conserved as well as specific roles in the soybean BR signaling network. Finally, the identification of two natural soybean varieties of the GmBZL3 mutantion by SNP analysis could facilitate the understanding of gene function during soybean development in the future. CONCLUSIONS: We illustrate here that GmBZL3 orchestrates a genome-wide transcriptional response that underlies BR-mediated soybean early vegetative growth, and our results support that BRs play crucial regulatory roles in soybean morphology and gene expression levels.

Determinants of postoperative left atrial structural reverse remodeling in patients undergoing combined catheter ablation of atrial fibrillation and left atrial appendage closure procedure.

INTRODUCTION: Catheter ablation of atrial fibrillation (AFCA) and left atrial appendage closure (LAAC) exert opposite effects on left atrial (LA) size. We aim to observe the net impact of combined AFCA and LAAC strategy on LA size and explore those factors which might affect the postprocedure LA structural remodeling. METHODS: A total of 53 patients, who underwent combined AFCA and Watchman LAAC in our center from March to December 2017, were enrolled. Atrial fibrillation (AF) recurrence was monitored after the procedure. Left atrial volume (LAV) and left atrial appendage volume (LAAV) were measured by Mimics based on dual-source computed tomography images. RESULTS: At 6 months, sinus rhythm (SR) was maintained in 79.2% patients. LAV was significantly reduced (130.2 ± 36.3 mL to 107.1 ± 30.0 ml; P < .001) in SR maintenance group, but not in AF recurrence group (138.8 ± 39.3 mL to 137.9 ± 36.9 mL; P = .671). In SR group, preoperative LAAV/LAV ratio (B = -0.894; P = .015), NT-proBNP (B = 0.005; P = .019) and left ventricular ejection fraction (LVEF) (B = -0.778; P < .001) could interactively affect the extent of postoperative LA structural reverse remodeling, among which LAAV/LAV ratio could independently predict the significance of reverse remodeling (≥15% reduction in LAV) (OR, 0.56; 95% CI, 0.34-0.90; P = .018). A preoperative LAAV/LAV ratio less than 7.1% is indicative of significant LA structural reverse remodeling in this patient cohort. CONCLUSIONS: LA structural reverse remodeling could be evidenced in patients with maintained SR following combined AFCA and LAAC. Smaller LAAV/LAV ratio, higher NT-proBNP or lower LVEF at baseline are associated with more significant LA structural reverse remodeling, while LAAV/LAV ratio can predict the significance of the process after one-stop treatment.

Soybean (Glycine max) SWEET gene family: insights through comparative genomics, transcriptome profiling and whole genome re-sequence analysis.

BACKGROUND: SWEET (MtN3_saliva) domain proteins, a recently identified group of efflux transporters, play an indispensable role in sugar efflux, phloem loading, plant-pathogen interaction and reproductive tissue development. The SWEET gene family is predominantly studied in Arabidopsis and members of the family are being investigated in rice. To date, no transcriptome or genomics analysis of soybean SWEET genes has been reported. RESULTS: In the present investigation, we explored the evolutionary aspect of the SWEET gene family in diverse plant species including primitive single cell algae to angiosperms with a major emphasis on Glycine max. Evolutionary features showed expansion and duplication of the SWEET gene family in land plants. Homology searches with BLAST tools and Hidden Markov Model-directed sequence alignments identified 52 SWEET genes that were mapped to 15 chromosomes in the soybean genome as tandem duplication events. Soybean SWEET (GmSWEET) genes showed a wide range of expression profiles in different tissues and developmental stages. Analysis of public transcriptome data and expression profiling using quantitative real time PCR (qRT-PCR) showed that a majority of the GmSWEET genes were confined to reproductive tissue development. Several natural genetic variants (non-synonymous SNPs, premature stop codons and haplotype) were identified in the GmSWEET genes using whole genome re-sequencing data analysis of 106 soybean genotypes. A significant association was observed between SNP-haplogroup and seed sucrose content in three gene clusters on chromosome 6. CONCLUSION: Present investigation utilized comparative genomics, transcriptome profiling and whole genome re-sequencing approaches and provided a systematic description of soybean SWEET genes and identified putative candidates with probable roles in the reproductive tissue development. Gene expression profiling at different developmental stages and genomic variation data will aid as an important resource for the soybean research community and can be extremely valuable for understanding sink unloading and enhancing carbohydrate delivery to developing seeds for improving yield.

Double-layer poly(vinyl alcohol)-coated capillary for highly sensitive and stable capillary electrophoresis and capillary electrophoresis with mass spectrometry glycan analysis.

Glycosylation plays an important role in protein conformations and functions as well as many biological activities. Capillary electrophoresis combined with various detection methods provided remarkable developments for high-sensitivity glycan profiling. The coating of the capillary is needed for highly polar molecules from complex biosamples. A poly(vinyl alcohol)-coated capillary is commonly utilized in the capillary electrophoresis separation of saccharides sample due to the high-hydrophilicity properties. A modified facile coating workflow was carried out to acquire a novel multiple-layer poly(vinyl alcohol)-coated capillary for highly sensitive and stable analysis of glycans. The migration time fluctuation was used as index in the optimization of layers and a double layer was finally chosen, considering both the effects and simplicity in fabrication. With migration time relative standard deviation less than 1% and theoretical plates kept stable during 100 consecutive separations, the method was presented to be suitable for the analysis of glycosylation with wide linear dynamic range and good reproducibility. The glycan profiling of enzymatically released N-glycans from human serum was obtained by the presented capillary electrophoresis method combined with mass spectrometry detection with acceptable results.

Comparison of Soybean Transformation Efficiency and Plant Factors Affecting Transformation during the Agrobacterium Infection Process.

The susceptibility of soybean genotype to Agrobacterium infection is a key factor for the high level of genetic transformation efficiency. The objective of this study is to evaluate the plant factors related to transformation in cotyledonary nodes during the Agrobacterium infection process. This study selected three genotypes (Williams 82, Shennong 9 and Bert) with high transformation efficiency, which presented better susceptibility to Agrobacterium infection, and three low transformation efficiency genotypes (General, Liaodou 16 and Kottman), which showed a relatively weak susceptibility. Gibberellin (GA) levels and soybean GA20ox2 and CYP707A2 transcripts of high-efficiency genotypes increased and were higher than those of low-efficiency genotypes; however, the opposite performance was shown in abscisic acid (ABA). Higher zeatin riboside (ZR) content and DNA quantity, and relatively higher expression of soybean IPT5, CYCD3 and CYCA3 were obtained in high-efficiency genotypes. High-efficiency genotypes had low methyl jasmonate (MeJA) content, polyphenol oxidase (PPO) and peroxidase (POD) activity, and relatively lower expression of soybean OPR3, PPO1 and PRX71. GA and ZR were positive plant factors for Agrobacterium-mediated soybean transformation by facilitating germination and growth, and increasing the number of cells in DNA synthesis cycle, respectively; MeJA, PPO, POD and ABA were negative plant factors by inducing defence reactions and repressing germination and growth, respectively.

A G-quadruplex based platform for label-free monitoring of DNA reaction kinetics.

Research on the kinetic characteristics and mechanisms of DNA reactions is crucial for bioengineering and biosensing. A G-quadruplex, which can form a peroxidase-mimicking DNAzyme with hemin, was for the first time used to establish a versatile platform for kinetic investigations on DNA reactions. G-quadruplex sequence EAD2 was incorporated into the corresponding nucleic acid reaction as product. The kinetic curves can be obtained rapidly and simply via the quantification of created DNAzyme. In this paper, the kinetics of isothermal linear strand displacement amplification reactions with different DNA lengths and isothermal exponential amplification reactions were successfully elucidated via the G-quadruplex based monitoring platform. As a safe and accessible alternative to the traditional methods, this robust, label-free, time-saving and high-throughput platform shows great potential for the exploration of more novel DNA reactions or circuits in an ingenious manner.

Hybridization chain reaction-based fluorescence immunoassay using DNA intercalating dye for signal readout.

A novel format of fluorescence immunosorbent assay based on the hybridization chain reaction (HCR) using a DNA intercalating dye for signal readout was constructed for the sensitive detection of targets, both in competitive and sandwich modes. In this platform, the capture and recognition processes are based on immunoreactions and the signal amplification depends on the enzyme-free, isothermal HCR-induced labelling event. After a competitive or a sandwich immunoreaction, a biotinylated capture DNA was bound to a biotinylated signal antibody through avidin, and triggered the HCR by two specific hairpins into a nicked double helix. Gene Finder (GF), a fluorescent probe for double-strand DNA, was intercalated in situ into the amplified chain to produce the fluorescence signal. The limit of detection (LOD) for rabbit IgG in competitive mode by HCR/GF immunoassay was improved at least 100-fold compared with the traditional fluorescence immunoassay using the fluorescein isothiocyanate-labelled-streptavidin or fluorescein isothiocyanate-labelled second antibody as the signal readout. The proposed fluorescence immunoassay was also demonstrated by using α-fetoprotein as the model target in sandwich mode, and showed a wide linear range from 28 ng mL(-1) to 20 µg mL(-1) with a LOD of 6.0 ng mL(-1). This method also showed satisfactory analysis in spiked human serum, which suggested that it might have great potential for versatile applications in life science and point-of-care diagnostics.

Nomogram establishment for short-term survival prediction in ICU patients with aplastic anemia based on the MIMIC-IV database.

OBJECTIVE: To establish an efficient nomogram model to predict short-term survival in ICU patients with aplastic anemia (AA). METHODS: The data of AA patients in the MIMIC-IV database were obtained and randomly assigned to the training set and testing set in a ratio of 7:3. Independent prognosis factors were identified through univariate and multivariate Cox regression analyses. The variance inflation factor was calculated to detect the correlation between variables. A nomogram model was built based on independent prognostic factors and risk scores for factors were generated. Model performance was tested using C-index, receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and Kaplan-Meier curve. RESULTS: A total of 1,963 AA patients were included. A nomogram model with 7 variables was built, including SAPS II, chronic pulmonary obstructive disease, body temperature, red cell distribution width, saturation of peripheral oxygen, age and mechanical ventilation. The C-indexes in the training set and testing set were 0.642 and 0.643 respectively, indicating certain accuracy of the model. ROC curve showed favorable classification performance of nomogram. The calibration curve reflected that its probabilistic prediction was reliable. DCA revealed good clinical practicability of the model. Moreover, the Kaplan-Meier curve showed that receiving mechanical ventilation could improve the survival status of AA patients in the short term but did not in the later period. CONCLUSION: The nomogram model of the short-term survival rate of AA patients was built based on clinical characteristics, and early mechanical ventilation could help improve the short-term survival rate of patients.

Effect of Acoustic Environment in Wards on Postoperative Rehabilitation in Patients with Oral Cancer: A Retrospective Study.

OBJECTIVE: The increase in patient flow, replacement of medical equipment, and variations in surrounding environments induce increasingly serious acoustic environment problems in hospitals. This study aims to provide additional bases for the formulation of subsequent management plans in clinical practice by analyzing the influence of the acoustic environment in wards and the postoperative rehabilitation effect among patients with oral cancer. METHODS: The medical records of 210 patients with oral cancer undergoing surgical treatment in Jinan Stomatological Hospital from February 2020 to October 2022 were selected for retrospective analysis. Patients with the acoustic environment in wards >55 and ≤55 dB were classified as groups A and B, respectively, according to the acoustic environment in wards. The effects of the acoustic environment in wards on postoperative blood pressure, blood viscosity, and blood glucose fluctuation (BGF) were observed to further analyze their relationship. RESULTS: No significant difference was observed in indices such as preoperative systolic pressure (SP), diastolic pressure (DP), cardiac output (CO), postoperative CO, total cholesterol, and low- and high-density lipoproteins between the two groups (P > 0.05). The SP, DP, whole blood low-shear viscosity (WBLSV), whole blood middle-shear viscosity (WBMSV), whole blood high-shear viscosity (WBHSV), and BGF in group B were significantly lower than group A (P < 0.05). Correlation results showed that the total mean value of the acoustic environment in wards was positively correlated with SP, DP, WBLSV, WBMSV, WBHSV, and BGF (P < 0.05). CONCLUSION: The high acoustic environment in wards is significantly positively correlated with postoperative blood pressure, blood viscosity, and BGF in patients with oral cancer. The hospital should focus on and strengthen the management of the acoustic environment in wards, providing additional schemes to promote the postoperative recovery of patients with oral cancer.

Biosynthesis of Chryseno[2,1,c]oxepin-12-Carboxylic Acid from Glycyrrhizic Acid in Aspergillus terreus TMZ05-2, and Analysis of Its Anti-inflammatory Activity.

Glycyrrhizic acid, glycyrrhetinic acid, and their oxo, ester, lactone, and other derivatives, are known for their anti-inflammatory, anti-oxidant, and hypoglycemic pharmacological activities. In this study, chryseno[2,1-c]oxepin-12-carboxylic acid (MG) was first biosynthesized from glycyrrhizic acid through sequential hydrolysis, oxidation, and esterification using Aspergillus terreus TMZ05-2, providing a novel in vitro biosynthetic pathway for glycyrrhizic acid derivatives. Assessing the influence of fermentation conditions and variation of strains during culture under stress-induction strategies enhanced the final molar yield to 88.3% (5 g/L glycyrrhizic acid). CCK8 assays showed no cytotoxicity and good cell proliferation, and anti-inflammatory experiments demonstrated strong inhibition of NO release (36.3%, low-dose MG vs. model), transcriptional downregulation of classical effective cellular factors tumor necrosis factor-α (TNF-α; 72.2%, low-dose MG vs. model), interleukin-6 (IL-6; 58.3%, low-dose MG vs. model) and interleukin-1ß (IL-1ß; 76.4%, low-dose MG vs. model), and decreased abundance of P-IKK-α, P-IKB-α, and P-P65 proteins, thereby alleviating inflammatory responses through the NF-κB pathway in LPS-induced RAW264.7 cells. The findings provide a reference for the biosynthesis of lactone compounds from medicinal plants.