Changes in metabolic parameters and serum YKL-40 levels in Chinese rheumatoid arthritis patients during tocilizumab therapy.

OBJECTIVE: To investigate the metabolic changes during therapy of tocilizumab (TCZ) and methotrexate (MTX) in non-diabetic rheumatoid arthritis (RA) patients and for the first time explore the associations between metabolic parameters and serum YKL-40 (sYKL-40) levels. METHODS: We enrolled active non-diabetic RA patients who were refractory to MTX. Patients received intravenous TCZ (8 mg/kg) once every 4 weeks combined with MTX for 24 weeks. Metabolic parameters and sYKL-40 levels were measured before TCZ infusion at baseline, week 4, week 12, and week 24. Correlations were assessed by the Spearman's rank correlation analysis. RESULTS: A total of 91 non-diabetic RA patients were enrolled in this study. At week 24, we observed a significant elevation in body mass index (BMI), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels. In contrast, there was a significant decrease in TC/HDL­C ratio. No apparent changes in insulin resistance were found. Additionally, we detected a significant reduction in sYKL-40 levels during the study. At week 24, changes in sYKL-40 levels showed a significant negative correlation (r = -0.334, p = 0.002) with changes in TC levels. CONCLUSION: The combined therapy of TCZ and MTX resulted in a significant increase in BMI and lipid levels, while an evident decrease in the TC/HDL­C ratio and sYKL-40 levels in RA patients. Additionally, there was a significant correlation between the decrease in sYKL-40 levels and the increase in TC levels during treatment with TCZ and MTX. Key Points • Lipid levels elevated significantly and sYKL-40 levels decreased obviously after therapy of TCZ combined with MTX in Chinese RA patients. • There was a significant correlation between the increase in TC levels and the decrease in sYKL-40 levels during treatment with TCZ and MTX in RA patients.

Two maize homologs of mammalian proton-coupled folate transporter, ZmMFS_1-62 and ZmMFS_1-73, are essential to salt and drought tolerance.

Folates are essential to the maintenance of normal life activities in almost all organisms. Proton-coupled folate transporter (PCFT), belonging to the major facilitator superfamily, is one of the three major folate transporter types widely studied in mammals. However, information about plant PCFTs is limited. Here, a genome-wide identification of maize PCFTs was performed, and two PCFTs, ZmMFS_1-62 and ZmMFS_1-73, were functionally investigated. Both proteins contained the typical 12 transmembrane helixes with N- and C-termini located in the cytoplasm, and were localized in the plasma membrane. Molecular docking analysis indicated their binding activity with folates via hydrogen bonding. Interference with ZmMFS_1-62 and ZmMFS_1-73 in maize seedlings through virus-induced gene silencing disrupted folate homeostasis, mainly in the roots, and reduced tolerance to drought and salt stresses. Moreover, a molecular chaperone protein, ZmHSP20, was found to interact with ZmMFS_1-62 and ZmMFS_1-73, and interference with ZmHSP20 in maize seedlings also led to folate disruption and increased sensitivity to drought and salt stresses. Overall, this is the first report of functional identification of maize PCFTs, which play essential roles in salt and drought stress tolerance, thereby linking folate metabolism with abiotic stress responses in maize.

Combined Use of Endoscopic Techniques and Virtual Surgical Planning for Intraoral Approach for Hemi-mandibular Resection and Reconstruction.

Background: The study aimed to describe our experience in using endoscopic procedures to aid hemi-mandibular reconstruction with bone flaps through transoral approach. Methods: Five patients with huge benign mandibular tumors underwent transoral mandibulectomy and hemi-mandibular reconstruction, using endoscopy. Facial symmetry, occlusion, bone healing, and mandibular similarity were all evaluated postoperatively. The paired-samples t test was used to compare quantitative data, and a P value less than 0.05 was considered a significant difference. Results: All five patients who received transoral mandibular surgery recovered in terms of TMJ functionality, facial symmetry, and aesthetic results. Endoscopy monitored and ensured that bone flaps were correctly connected and fixed. The accuracy of endoscopy-guided mandibular reconstruction was confirmed by quantitative examination for four cases, which revealed no statistically significant variations between postoperative CT analysis and preoperative virtual surgical planning data. Conclusions: Endoscopy-assisted virtual surgery may resolve concerns with transoral hemi-mandibular reconstruction and broaden indications for mini-invasive mandibular reconstruction. However, only patients with benign mandibular tumors were included in our study, so surgeons should be very cautious if applying this technique to malignant lesions or bony tumors invading soft tissues.

Causal associations between gut microbiota, metabolites and asthma: a two-sample Mendelian randomization study.

BACKGROUND: While several traditional observational studies have suggested associations between gut microbiota and asthma, these studies are limited by factors such as participant selection bias, confounders, and reverse causality. Therefore, the causal relationship between gut microbiota and asthma remains uncertain. METHODS: We performed two-sample bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationships between gut microbiota and asthma as well as its phenotypes. We also conducted MR analysis to evaluate the causal effect of gut metabolites on asthma. Genetic variants for gut microbiota were obtained from the MiBioGen consortium, GWAS summary statistics for metabolites from the TwinsUK study and KORA study, and GWAS summary statistics for asthma from the FinnGen consortium. The causal associations between gut microbiota, gut metabolites and asthma were examined using inverse variance weighted, maximum likelihood, MR-Egger, weighted median, and weighted model and further validated by MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis. RESULTS: We identified nine gut microbes whose genetically predicted relative abundance causally impacted asthma risk. After FDR correction, significant causal relationships were observed for two of these microbes, namely the class Bacilli (OR = 0.84, 95%CI = 0.76-0.94, p = 1.98 × 10-3) and the order Lactobacillales (OR = 0.83, 95%CI = 0.74-0.94, p = 1.92 × 10-3). Additionally, in a reverse MR analysis, we observed a causal effect of genetically predicted asthma risk on the abundance of nine gut microbes, but these associations were no longer significant after FDR correction. No significant causal effect of gut metabolites was found on asthma. CONCLUSIONS: Our study provides insights into the development mechanism of microbiota-mediated asthma, as well as into the prevention and treatment of asthma through targeting specific gut microbiota.

Association between n-3 PUFA and lung function: results from the NHANES 2007-2012 and Mendelian randomisation study.

This study aimed to investigate the association between n-3 PUFA and lung function. First, a cross-sectional study was conducted based on the National Health and Nutrition Examination Survey (NHANES) 2007-2012 data. n-3 PUFA intake was obtained from 24-h dietary recalls. A multivariable linear regression model was used to assess the observational associations of n-3 PUFA intake with lung function. Subsequently, a two-sample Mendelian randomisation (MR) was performed to estimate the potential causal effect of n-3 PUFA on lung function. Genetic instrumental variables were extracted from published genome-wide association studies. Summary statistics about n-3 PUFA was from UK Biobank. Inverse variance weighted was the primary analysis approach. The observational study did not demonstrate a significant association between n-3 PUFA intake and most lung function measures; however, a notable exception was observed with significant findings in the highest quartile for forced vital capacity (FVC) and % predicted FVC. The MR results also showed no causal effect of circulating n-3 PUFA concentration on lung function (forced expiratory volume in one second (FEV1), ß = 0·01301, se = 0·01932, P = 0·5006; FVC, ß = -0·001894, se = 0·01704, P = 0·9115; FEV1:FVC, ß = 0·03118, se = 0·01743, P = 0·07359). These findings indicate the need for further investigation into the impact of higher n-3 PUFA consumption on lung health.

Efficacy of omalizumab in adult patients with allergic bronchopulmonary aspergillosis: a multicentre study in China.

Despite conventional glucocorticoid and antifungal therapy, acute exacerbation and hospitalization occur frequently in patients with allergic bronchopulmonary aspergillosis (ABPA). Whether omalizumab is an effective and safe treatment for adult patients with ABPA complicating asthma. Patients with ABPA complicating asthma who were treated with omalizumab from October 2019 to May 2023 were collected from five tertiary hospitals and evaluated. The frequencies of acute exacerbation and hospitalization; the number of eosinophils; the total IgE levels; and the average monthly medical dosages after 3, 6, and 12 months of omalizumab treatment were analysed, and the data before and after treatment (up to one year) were compared. The efficacy and safety of omalizumab treatment were assessed. In total, 26 patients were enrolled. The average monthly glucocorticoid dosage significantly decreased (median 0 vs. 24 mg/m) after 6 months of omalizumab treatment compared with 3 months; 73.68% of patients discontinued glucocorticoids after ≤ 12 months of treatment. Similarly, the average monthly dosage of antifungal agents was significantly decreased (median 0 vs. 3.49 g/m) after 12 months of treatment compared with 3 months. The average monthly glucocorticoid dosage (median 213.75 vs. 65.42 mg/m, P = 0.002) and the frequency of acute exacerbation (median 0.94 vs. 0.44 events, P = 0.033) were considerably reduced after omalizumab treatment. Omalizumab is effective in reducing the frequency of acute exacerbation and the necessary dosage of glucocorticoids in adult patients with ABPA complicating asthma. Patient age and BMI may affect the efficacy of treatment.

Harnessing microbial interactions with rice: Strategies for abiotic stress alleviation in the face of environmental challenges and climate change.

Rice, which feeds more than half of the world's population, confronts significant challenges due to environmental and climatic changes. Abiotic stressors such as extreme temperatures, drought, heavy metals, organic pollutants, and salinity disrupt its cellular balance, impair photosynthetic efficiency, and degrade grain quality. Beneficial microorganisms from rice and soil microbiomes have emerged as crucial in enhancing rice's tolerance to these stresses. This review delves into the multifaceted impacts of these abiotic stressors on rice growth, exploring the origins of the interacting microorganisms and the intricate dynamics between rice-associated and soil microbiomes. We highlight their synergistic roles in mitigating rice's abiotic stresses and outline rice's strategies for recruiting these microorganisms under various environmental conditions, including the development of techniques to maximize their benefits. Through an in-depth analysis, we shed light on the multifarious mechanisms through which microorganisms fortify rice resilience, such as modulation of antioxidant enzymes, enhanced nutrient uptake, plant hormone adjustments, exopolysaccharide secretion, and strategic gene expression regulation, emphasizing the objective of leveraging microorganisms to boost rice's stress tolerance. The review also recognizes the growing prominence of microbial inoculants in modern rice cultivation for their eco-friendliness and sustainability. We discuss ongoing efforts to optimize these inoculants, providing insights into the rigorous processes involved in their formulation and strategic deployment. In conclusion, this review emphasizes the importance of microbial interventions in bolstering rice agriculture and ensuring its resilience in the face of rising environmental challenges.

Clinical features of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with macrophage activation syndrome.

OBJECTIVES: This study aimed to describe the clinical features of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) who had macrophage activation syndrome (MAS). METHODS: We retrospectively examined 44 patients with anti-MDA5-positive DM and compared the clinical features between patients with MAS (n = 11) and those without (n=33). Patients without MAS were selected randomly in the same year as those with MAS at a ratio of 3:1. Among patients with MAS, we compared the features between non-survivors and survivors. We used Fisher's exact test, Student's t test, the Mann-Whitney U test and the log-rank test for statistical analysis. RESULTS: Patients complicated with MAS had a significantly higher incidence of infection, heliotrope sign, Gottron's papule, V-neck sign, and higher serum levels of ferritin, aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) than those without MAS (p<0.05). Among the 11 patients with MAS, 4 (36.4%) died after intensive treatment. Deceased patients were older, given more combination therapy with tofacitinib (TOF) and had a higher incidence of rapid progressive interstitial lung disease, infection, heart failure and renal impairment than those who survived (p<0.05). CONCLUSIONS: Among anti-MDA5-positive DM, Infection, DM typical rashes, and higher serum levels of ferritin, AST, LDH, and CK were more common in patients complicated with MAS. The mortality of patients with MAS was high, particularly among patients who were older, given more combination therapy with TOF, and had RP-ILD, infection, heart failure and renal impairment.

FGL1 in plasma extracellular vesicles is correlated with clinical stage of lung adenocarcinoma and anti-PD-L1 response.

Fibrinogen-like protein-1 (FGL1) is confirmed a major ligand of lymphocyte activation gene-3 which could inhibit antigen-mediated T-cell response and evade immune supervision. Although hepatocytes secrete large amounts of FGL1, its high expression also be detected in solid tumors such as lung cancer, leading to a poor efficacy of immune checkpoint inhibitors therapy. Here we reported that FGL1 was overexpressed in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma. However, FGL1 in tissue and plasma can only distinguish LUAD patients from healthy donors and cannot correlate with clinical Tumor Node Metastasis (TNM) stage. Using lung cancer cell lines, we confirmed that FGL1 can be detected on extracellular vesicles (EVs) and we established a method using flow cytometry to detect FGL1 on the surface of EVs, which revealed that FGL1 could be secreted via EVs. Both animal model and clinical samples proved that plasma FGL1 in EVs would increase when the tumor was loaded. The level of FGL1 in plasma EVs was correlated with clinical TNM stage and tumor size, and a higher level indicated non-responsiveness to anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy. Its effect on tumor progression and immune evasion may be achieved by impairing the killing and proliferating capacities of CD8+ T cells. Our result demonstrates that FGL1 levels in plasma EVs, but not total plasma FGL1, could be a promising biomarker that plays an important role in predicting anti-PD-L1 immune therapy in LUAD and suggests a new strategy in LUAD immunotherapy.

Application of Methionine Increases the Germination Rate of Maize Seeds by Triggering Multiple Phenylpropanoid Biosynthetic Genes at Transcript Levels.

Methionine is an essential amino acid that initiates protein synthesis and serves as a substrate for various chemical reactions. Methionine metabolism plays an important role in Arabidopsis seed germination, but how methionine works in seed germination of maize has not been elucidated. We compared the changes in germination rate, the contents of methionine and folates, and transcriptional levels using transcriptome analysis under water or exogenous methionine treatment. The results indicate that the application of methionine increases seed germination rate (95% versus 70%), leading to significant differences in the content of methionine at 36 h, which brought the rapid increase forward by 12 h in the embryo and endosperm. Transcriptome analysis shows that methionine mainly affects the proliferation and differentiation of cells in the embryo, and the degradation of storage substances and signal transduction in the endosperm. In particular, multiple phenylpropanoid biosynthetic genes were triggered upon methionine treatment during germination. These results provide a theoretical foundation for promoting maize seed germination and serve as a valuable theoretical resource for seed priming strategies.

Why Dissolving Salt in Water Decreases Its Dielectric Permittivity.

The dielectric permittivity of salt water decreases on dissolving more salt. For nearly a century, this phenomenon has been explained by invoking saturation in the dielectric response of the solvent water molecules. Herein, we employ an advanced deep neural network (DNN), built using data from density functional theory, to study the dielectric permittivity of sodium chloride solutions. Notably, the decrease in the dielectric permittivity as a function of concentration, computed using the DNN approach, agrees well with experiments. Detailed analysis of the computations reveals that the dominant effect, caused by the intrusion of ionic hydration shells into the solvent hydrogen-bond network, is the disruption of dipolar correlations among water molecules. Accordingly, the observed decrease in the dielectric permittivity is mostly due to increasing suppression of the collective response of solvent waters.

Clinical characteristics and prognosis in systemic lupus erythematosus-associated pulmonary arterial hypertension based on consensus clustering and risk prediction model.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE). This study aims to explore the clinical characteristics and prognosis in SLE-PAH based on consensus clustering and risk prediction model. METHODS: A total of 205 PAH (including 163 SLE-PAH and 42 idiopathic PAH) patients were enrolled retrospectively based on medical records at the First Affiliated Hospital of Zhengzhou University from July 2014 to June 2021. Unsupervised consensus clustering was used to identify SLE-PAH subtypes that best represent the data pattern. The Kaplan-Meier survival was analyzed in different subtypes. Besides, the least absolute shrinkage and selection operator combined with Cox proportional hazards regression model were performed to construct the SLE-PAH risk prediction model. RESULTS: Clustering analysis defined two subtypes, cluster 1 (n = 134) and cluster 2 (n = 29). Compared with cluster 1, SLE-PAH patients in cluster 2 had less favorable levels of poor cardiac, kidney, and coagulation function markers, with higher SLE disease activity, less frequency of PAH medications, and lower survival rate within 2 years (86.2% vs. 92.8%) (P < 0.05). The risk prediction model was also constructed, including older age at diagnosis (≥ 38 years), anti-dsDNA antibody, neuropsychiatric lupus, and platelet distribution width (PDW). CONCLUSIONS: Consensus clustering identified two distinct SLE-PAH subtypes which were associated with survival outcomes. Four prognostic factors for death were discovered to construct the SLE-PAH risk prediction model.

A new nomogram for the individualized prediction of children's mortality risk in pediatric intensive care unit.

OBJECTIVE: We developed a new nomogram for the prediction of mortality risk in children in pediatric intensive care units (PICU). METHODS: We conducted a retrospective analysis using the PICU Public Database, a study that included a total of 10,538 children, to develop a new risk model for mortality in children in the intensive care units (ICU). The prediction model was analyzed using multivariate logistic regression with predictors including age and physiological indicators, and the prediction model was presented as a nomogram. The performance of the nomogram was evaluated based on its discriminative power and was internally validated. RESULTS: Predictors contained in the individualized prediction nomogram included the neutrophils, platelets, albumin, lactate, oxygen saturation (P<0.1). The area under the receiver operating characteristic (ROC) curve for this prediction model is 0.7638 (95% CI: 0.7415-0.7861), which has effective discriminatory power. The area under the ROC curve of the prediction model in the validation dataset is 0.7404 (95% CI: 0.7016-0.7793), which is still effectively discriminative. CONCLUSION: The mortality risk prediction model constructed in this study can be easily used for individualized prediction of mortality risk in children in pediatric intensive care units.

New Genes Identified as Modulating Salt Tolerance in Maize Seedlings Using the Combination of Transcriptome Analysis and BSA.

(1) Background: Salt stress is an abiotic factor that limits maize yield and quality. A highly salt-tolerance inbred AS5 and a salt-sensitive inbred NX420 collected from Ningxia Province, China, were used to identify new genes for modulating salt resistance in maize. (2) Methods: To understand the different molecular bases of salt tolerance in AS5 and NX420, we performed BSA-seq using an F2 population for two extreme bulks derived from the cross between AS5 and NX420. Transcriptomic analysis was also conducted for AS5 and NX420 at the seedling stage after treatment with 150 mM of NaCl for 14 days. (3) Results: AS5 had a higher biomass and lower Na+ content than NX420 in the seedling stage after treatment with 150 mM NaCl for 14 days. One hundred and six candidate regions for salt tolerance were mapped on all of the chromosomes through BSA-seq using F2 in an extreme population. Based on the polymorphisms identified between both parents, we detected 77 genes. A large number of differentially expressed genes (DEGs) at the seedling stage under salt stress between these two inbred lines were detected using transcriptome sequencing. GO analysis indicated that 925 and 686 genes were significantly enriched in the integral component of the membrane of AS5 and NX420, respectively. Among these results, two and four DEGs were identified as overlapping in these two inbred lines using BSA-seq and transcriptomic analysis, respectively. Two genes (Zm00001d053925 and Zm00001d037181) were detected in both AS5 and NX420; the transcription level of Zm00001d053925 was induced to be significantly higher in AS5 than in NX420 (41.99 times versus 6.06 times after 150 mM of NaCl treatment for 48 h), while the expression of Zm00001d037181 showed no significant difference upon salt treatment in both lines. The functional annotation of the new candidate genes showed that it was an unknown function protein. (4) Conclusions: Zm00001d053925 is a new functional gene responding to salt stress in the seedling stage, which provides an important genetic resource for salt-tolerant maize breeding.

Omega-3 polyunsaturated fatty acids ameliorate PM2.5 exposure induced lung injury in mice through remodeling the gut microbiota and modulating the lung metabolism.

Short-term or long-term exposure to fine particulate matter (PM2.5) is related to increased incidences of respiratory diseases. This study aimed to investigate the influences of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) supplementation on oxidative stress, inflammation, lung metabolic profile, and gut microbiota in PM2.5-induced lung injury mice. Mice were divided into four groups (n = 15, per group): two unsupplemented groups, control group and PM2.5 group, and two supplemented groups with ω-3 PUFAs, ω-3 PUFAs group, and ω-3 PUFAs + PM2.5 group. Mice in the supplemented groups were placed on an ω-3 PUFAs-enriched diet (ω-3 PUFAs, 21 g/kg). During the 5th to 6th week of dietary supplementation, mice were exposed to PM2.5 by intra-tracheal instillation. ω-3 PUFAs ameliorate lung histopathological injury, reduce inflammatory responses and oxidative stress, affect lung metabolite profile, and modulate gut microbiota in PM2.5-induced lung injury mice. Thus, supplementary ω-3 PUFAs showed effectiveness in attenuation of PM2.5-induced lung injury, indicating that the interventions exhibited preventive and therapeutic potential.

Integration of high-throughput phenotyping, GWAS, and predictive models reveals the genetic architecture of plant height in maize.

Plant height (PH) is an essential trait in maize (Zea mays) that is tightly associated with planting density, biomass, lodging resistance, and grain yield in the field. Dissecting the dynamics of maize plant architecture will be beneficial for ideotype-based maize breeding and prediction, as the genetic basis controlling PH in maize remains largely unknown. In this study, we developed an automated high-throughput phenotyping platform (HTP) to systematically and noninvasively quantify 77 image-based traits (i-traits) and 20 field traits (f-traits) for 228 maize inbred lines across all developmental stages. Time-resolved i-traits with novel digital phenotypes and complex correlations with agronomic traits were characterized to reveal the dynamics of maize growth. An i-trait-based genome-wide association study identified 4945 trait-associated SNPs, 2603 genetic loci, and 1974 corresponding candidate genes. We found that rapid growth of maize plants occurs mainly at two developmental stages, stage 2 (S2) to S3 and S5 to S6, accounting for the final PH indicators. By integrating the PH-association network with the transcriptome profiles of specific internodes, we revealed 13 hub genes that may play vital roles during rapid growth. The candidate genes and novel i-traits identified at multiple growth stages may be used as potential indicators for final PH in maize. One candidate gene, ZmVATE, was functionally validated and shown to regulate PH-related traits in maize using genetic mutation. Furthermore, machine learning was used to build predictive models for final PH based on i-traits, and their performance was assessed across developmental stages. Moderate, strong, and very strong correlations between predictions and experimental datasets were achieved from the early S4 (tenth-leaf) stage. Colletively, our study provides a valuable tool for dissecting the spatiotemporal formation of specific internodes and the genetic architecture of PH, as well as resources and predictive models that are useful for molecular design breeding and predicting maize varieties with ideal plant architectures.

DeePKS + ABACUS as a Bridge between Expensive Quantum Mechanical Models and Machine Learning Potentials.

Recently, the development of machine learning (ML) potentials has made it possible to perform large-scale and long-time molecular simulations with the accuracy of quantum mechanical (QM) models. However, for different levels of QM methods, such as density functional theory (DFT) at the meta-GGA level and/or with exact exchange, quantum Monte Carlo, etc., generating a sufficient amount of data for training an ML potential has remained computationally challenging due to their high cost. In this work, we demonstrate that this issue can be largely alleviated with Deep Kohn-Sham (DeePKS), an ML-based DFT model. DeePKS employs a computationally efficient neural network-based functional model to construct a correction term added upon a cheap DFT model. Upon training, DeePKS offers closely matched energies and forces compared with high-level QM method, but the number of training data required is orders of magnitude less than that required for training a reliable ML potential. As such, DeePKS can serve as a bridge between expensive QM models and ML potentials: one can generate a decent amount of high-accuracy QM data to train a DeePKS model and then use the DeePKS model to label a much larger amount of configurations to train an ML potential. This scheme for periodic systems is implemented in a DFT package ABACUS, which is open source and ready for use in various applications.

Diabetes associated with HPV infection in women aged over 50 years: A cross-sectional study from China's largest academic woman's hospital.

Background: Metabolic disturbances and immune alterations caused by diabetes are not just bystanders of HPV infection, but the conclusion that diabetes increases the risk of HPV infection requires more clinical epidemiological evidence to confirm. Our aim was to evaluate the association of diabetes with HPV infection risk in female patients aged over 50 years in the cervical clinic. Methods: We conducted a cross-sectional study of 6402 women aged over 50 years in the cervical clinic between May 2019 and March 2022 from China's largest academic woman's hospital. The quantitative-effect relationship between diabetes and HPV infection was observed by dose-response graph. Segmented multivariate logistic regression analysis was conducted to estimate the relative risk of HPV infection in diabetes patients. Multivariable predicted marginal proportions from logistic regression models were used to compute adjusted risk ratios. Results: There is a nonlinear relationship between HbA1c and the risk of HPV infection. When the HbA1c exceeds 5.7%, there is a saturation effect. After adjustment for confounders, the risk ratio for HPV infection in women with prediabetes was 1.09 (95% CI: 1.00-1.18) compared with women with HbA1c <5.7%, and the risk ratio for HPV infection in women with diabetes was 1.18 (95%). CI: 1.04-1.33). Sensitivity analysis showed that the risk ratio for HPV infection was 1.47 (95% CL: 1.07-1.91) when diabetes was associated with vaginitis. E-value analysis suggested robustness to unmeasured confounding. Conclusions: Diabetes and prediabetes are at increased risk of coinfection with HPV in female patients aged over 50 years in the cervical clinic.

Reduced serum cholinesterase is an independent risk factor for all-cause mortality in the pediatric intensive care unit.

Objective: Our aim was to assess the relationship between serum cholinesterase levels at intensive care unit admission and all-cause mortality in the pediatric intensive care unit. Methods: We used the pediatric intensive care unit database (a large pediatric intensive care database in China from 2010 to 2018) to conduct a retrospective analysis to evaluate the serum cholinesterase levels at intensive care unit admission of 11,751 critically ill children enrolled to the intensive care unit. We analyzed the association between serum cholinesterase and all-cause mortality. Adjusted smoothing spline plots, subgroup analysis and segmented multivariate logistic regression analysis were conducted to estimate the relative risk between proportional risk between serum cholinesterase and death. Results: Of the 11,751 children, 703 (5.98%) died in hospital. After adjusting for confounders, there was a negative association between serum cholinesterase and the risk of death in pediatric intensive care unit. For every 1,000 U/L increase in serum cholinesterase, the risk of death was reduced by 16% (adjusted OR = 0.84, 95% CI: 0.79, 0.89). The results of sensitivity analysis showed that in different stratified analyses (age, intensive care unit category, albumin, alanine aminotransferase, creatinine, neutrophils), the effect of serum cholinesterase on all-cause mortality remained stable. Conclusion: After adjusting for inflammation, nutrition, and liver function factors, cholinesterase reduction is still an independent risk factor for pediatric intensive care unit all-cause mortality.