tRNA-derived fragments: Unveiling new roles and molecular mechanisms in cancer progression.

tRNA-derived fragments (tRFs) are novel small noncoding RNAs (sncRNAs) that range from approximately 14 to 50 nt. They are generated by the cleavage of mature tRNAs or precursor tRNAs (pre-tRNAs) at specific sites. Based on their origin and length, tRFs can be classified into three categories: (1) tRF-1 s; (2) tRF-3 s, tRF-5 s, and internal tRFs (i-tRFs); and (3) tRNA halves. They play important roles in stress response, signal transduction, and gene expression processes. Recent studies have identified differential expression of tRFs in various tumors. Aberrantly expressed tRFs have critical clinical value and show promise as new biomarkers for tumor diagnosis and prognosis and as therapeutic targets. tRFs regulate the malignant progression of tumors via various mechanisms, primarily including modulation of noncoding RNA biogenesis, global chromatin organization, gene expression regulation, modulation of protein translation, regulation of epigenetic modification, and alternative splicing regulation. In conclusion, tRF-mediated regulatory pathways could present new avenues for tumor treatment, and tRFs could serve as promising therapeutic targets for cancer therapy.

The role of NAD-dependent deacetylase sirtuin-2 in liver metabolic stress through regulating pyruvate kinase M2 ubiquitination.

NAD-dependent deacetylase Sirt2 is involved in mammalian metabolic activities, matching energy demand with energy production and expenditure, and is relevant to a variety of metabolic diseases. Here, we constructed Sirt2 knockout and adeno-associated virus overexpression mice and found that deletion of hepatic Sirt2 accelerated primary obesity and insulin resistance in mice with concomitant hepatic metabolic dysfunction. However, the key targets of Sirt2 are unknown. We identified the M2 isoform of pyruvate kinase (PKM2) as a key Sirt2 target involved in glycolysis in metabolic stress. Through yeast two-hybrid and mass spectrometry combined with multi-omics analysis, we identified candidate acetylation modification targets of Sirt2 on PKM2 lysine 135 (K135). The Sirt2-mediated deacetylation-ubiquitination switch of PKM2 regulated the development of glycolysis. Here, we found that Sirt2 deficiency led to impaired glucose tolerance and insulin resistance and induced primary obesity. Sirt2 severely disrupted liver function in mice under metabolic stress, exacerbated the metabolic burden on the liver, and affected glucose metabolism. Sirt2 underwent acetylation modification of lysine 135 of PKM2 through a histidine 187 enzyme active site-dependent effect and reduced ubiquitination of the K48 ubiquitin chain of PKM2. Our findings reveal that the hepatic glucose metabolism links nutrient state to whole-body energetics through the rhythmic regulation of Sirt2.

Effects of rhythm-control and rate-control strategies on cognitive function and dementia in atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that atrial fibrillation (AF) is an independent risk factor for cognitive impairment and dementia, even in the absence of thromboembolic events and stroke. Whether rhythm-control therapy can protect cognitive function remains unclear. We aimed to evaluate the efficacy of rhythm-control strategies in patients with AF regarding cognitive function and dementia risk. METHODS: We systematically searched the PubMed, Embase and Cochrane Library databases for randomised clinical trials, cohort and case-control studies evaluating the associations between rhythm-control strategies and cognitive function outcomes up to May 2023. We assessed the risk of bias using the ROBINS-I and the Cochrane risk-of-bias tool. Both fixed- and random-effects models were used to create summary estimates of risk. RESULTS: We included a total of 14 studies involving 193,830 AF patients. In the pooled analysis, compared with rate-control, rhythm-control therapy was significantly associated with a lower risk of future dementia (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.62-0.89; I2 = 62%). Among the rhythm-control strategies, AF ablation is a promising treatment that was related to significantly lower risks of overall dementia (HR 0.62; 95% CI 0.56-0.68; I2 = 42%), Alzheimer's disease (HR 0.78; 95% CI 0.66-0.92; I2 = 0%) and vascular dementia (HR 0.58; 95% CI 0.42-0.80; I2 = 31%). Pooled results also showed that compared with patients without ablation, those who underwent AF ablation had significantly greater improvement in cognitive score (standardized mean difference (SMD) 0.85; 95% CI 0.30-1.40; P = 0.005; I2 = 76%). CONCLUSIONS: Rhythm-control strategies, especially ablation, are effective in protecting cognitive function, reducing dementia risk and thus improving quality of life in AF patients.

M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis.

BACKGROUND: Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms. METHODS: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated ß-gal (SA-ß-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed. RESULTS: Herein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the m6A demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition. CONCLUSION: H-Exs secreted circBRCA1 regulated by m6A modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.

Associations of latent patterns of parent‒child communication with communication quality and mental health outcomes among Chinese left-behind children.

BACKGROUND: Parent‒child communication in migrant families is essential to family bonds and the mental health of left-behind children (LBC). Little is known about the different patterns of communication between migrant parents and LBC and associated communication quality and mental health outcomes. METHODS: A sample of 2,183 Chinese children (mean age = 12.95 ± 1.29 years) from Anhui province, including LBC whose parents had both migrated (n = 1,025) and children whose parents had never migrated (never-LBC, n = 1,158), was analyzed. With the LBC sample, latent class analysis was applied to identify the patterns of parent‒child communication. Multinomial logistic regression analysis was conducted to assess the associations between the sociodemographic variables and class membership of LBC. Analysis of covariance and chi-square tests were used to compare communication quality and mental health outcome differences among the classes of LBC and between each of the classes and never-LBC. RESULTS: Five latent classes of communication formed through different media or channels between migrant parents and their LBC were identified. Higher household economic status (OR = 2.81, p < 0.05) was associated with adequate communication. LBC in Class 1, defined by frequent technologically-mediated and face-to-face communication, had a significantly higher quality of communication with their migrant parents (F = 8.92, p < 0.001) and better mental health than those in other latent classes; these children did not have significantly worse mental health outcomes compared to never -LBC. CONCLUSIONS: Facilitating multichannel parent‒child communication is a practical way of reducing mental health inequities between LBC and their peers.

Single-cell transcriptional profiling uncovers the association between EOMES+CD8+ T cells and acquired EGFR-TKI resistance.

Acquired resistance to tyrosine kinase inhibitors (TKIs) is reportedly inevitable in lung cancers harboring epidermal growth factor receptor (EGFR) mutations, emphasizing the need for novel approaches to predict EGFR-TKI resistance for clinical monitoring and patient management. This study identified a significant increase in eomesodermin (EOMES)+CD8+ T cells in the TKI-resistant patients, which was correlated with poor survival. The increase in EOMES+CD8+ T cells was further confirmed in both tissue samples and peripheral blood of patients with TKIs resistance. The integrated analysis of pseudotime and Gene set variation showed that the increase in EOMES+CD8+ T cells may be attributed to TRM T cell conversion and metabolic reprogramming. Overall, this work suggested an association between the increased number of EOMES+CD8+ T cells and acquired TKI drug resistance, supporting the utility of EOMES+CD8+ T cells as a biomarker for TKI treatment response.

Nutritional improvement status of primary and secondary school students in the pilot nutrition improvement areas of Hainan, China from 2014 to 2021.

OBJECTIVE: By meticulously tracking the evolving growth, development, and nutritional status of primary and secondary school students in Qiongzhong County from 2014 to 2021 post-implementation of the "Nutrition Improvement Program for Rural Compulsory Education Students"(NIPRCES, This project provides a supplementary food allowance of at least ï¿¥4 per person per day for primary and secondary school students. The project area undergoes annual routine monitoring.), this study aims to offer a scientific basis for enhancing and promoting the project. Through thorough monitoring of students' nutritional status changes influenced by this program, we strive to establish a comprehensive and evidence-based framework for its future advancement. METHODS: From 2014 to 2021, this study employed a multi-stage sampling method utilizing cluster sampling to select six primary and six secondary schools in Qiongzhong County, Hainan Province. Data on the growth and development of respondents were collected. This cohort was a dynamic cohort with a total of 18,762 final data recovered. The prevalence of malnutrition was evaluated using the Cochran Armitage Trend Test (CATT) to assess year-to-year changes. Furthermore, height/weight and the prevalence of malnutrition between groups were compared using the t-test, χ2 test, and Bonferroni's corrected analysis. RESULTS: The average height of both boys and girls has increased. In 2021, boys and girls of all ages showed an average height increase of 2.31 cm and 1.98 cm, respectively, compared to 2014. Nevertheless, the growth and development levels, and rate of improvement of these students remain comparatively lower than their rural counterparts across China, who are of the same age. From 2014 to 2021, the prevalence of undernutrition (mainly wasting) showed a significant downward trend (P < 0.05) from 29.30% to 22.19%, and the prevalence of overnutrition showed an upward trend (both P < 0.05). The prevalence of undernutrition was higher among boys, students in grades 1-3 and those of Li nationality. Meanwhile, the prevalence of overnutrition was higher among boys, students in grades 1-3 and those of Han nationality. CONCLUSIONS: Over the 8-year period of NIPRCES, there has been progress in the growth and development of students, yet levels still lag behind the national average for rural students of the same age. While malnutrition prevalence have decreased, they remain high, with a concerning rise in overnutrition prevalence. Undernutrition and overweight/obesity are more prevalent among boys and younger students. Li students show higher prevalence of undernutrition, while overnutrition is a growing issue among Han students. Simultaneously, local education and health care departments must acknowledge the disparities in growth and nutritional status among primary and secondary school students residing in rural areas within the tropics and those in rural areas across the entire nation. Nutritional improvement measures should be tailored to local conditions.

Chronic exercise improves renal AT1 and ETB receptor functions via modulating GRK4 expression in obese Zucker rats.

BACKGROUND: Physical activity has profound benefits on health, especially in patients with cardiovascular and metabolic disease. Exercise training can reduce oxidative stress, improve renal function, and thus lower blood pressure. However, the effect of exercise training on angiotensin II type 1 receptors (AT1R) and endothelin subtype B receptors (ETBR)-mediated diuresis and natriuresis in obese Zucker rats is unclear. METHODS: Lean and obese Zucker rats were exercised or placed on a nonmoving treadmill for 8 weeks. Blood pressure was measured by tail-cuff plethysmography, and functions of AT1R and ETBR in the kidney were measured by natriuresis, respectively. RESULTS: Our data showed that exercise training improved glucose and lipid metabolism, renal function and sodium excretion in obese Zucker rats, accompanied by decreased oxidative stress and GRK4 expression in obese Zucker rats. Moreover, exercise training reduced the Candesartan-induced an increase in diuresis and natriuresis and increased ETBR agonists (BQ3020)-mediated diuresis and natriuresis in obese Zucker rats, which were associated with decreased renal AT1R expression and ETBR phosphorylation levels. CONCLUSIONS: The results demonstrate that exercise training lowers blood pressure via improving renal AT1R and ETBR function through modulating GRK4 expression in Obese Zucker Rats and provides potentially effective targets for obesity-related hypertension.

Ivabradine Alleviates Experimental Autoimmune Myocarditis-Mediated Myocardial Injury.

Ivabradine (IVA) reduces heart rate by inhibiting hyperpolarization-activated cyclic nucleotide-gated channels (HCNs), which play a role in the promotion of pacemaker activity in cardiac sinoatrial node cells. HCNs are highly expressed in neural and myocardial tissues and are involved in the modulation of inflammatory neuropathic pain. However, whether IVA exerts any effect on myocardial inflammation in the pathogenesis of heart failure is unclear. We employed single-cell RNA sequencing (scRNA-seq) in porcine cardiac myosin-induced experimental autoimmune myocarditis rat model to determine the effects and mechanisms of IVA. Lewis rats (n = 32) were randomly divided into the normal, control, high-dose-IVA, and low-dose-IVA groups. Heart rate and blood pressure were measured on days 0 and 21, respectively. Echocardiography was performed on day 22, and inflammation of the myocardium was evaluated via histopathological examination. Western blot was employed to detect the expression of HCN1-4, MinK-related protein 1 (MiRP1), matrix metalloproteinase 2 (MMP-2), MMP-9, and transforming growth factor-ß (TGF-ß). Furthermore, enzyme-linked immunosorbent assay was performed to measure serum IL-1, IL-6, and TNF-α. The relative mRNA levels of collagen I, collagen III, and α-smooth muscle actin (α-SMA) were determined via qRT-PCR. We found that IVA reduced the total number of cells infiltrated into the myocardium, particularly in the subset of fibroblasts, endocardia, and monocytes. IVA administration ameliorated cardiac inflammation and reduced collagen production. Results of the echocardiography indicated that left ventricular internal diameter at end-systole LVIDs increased whereas left ventricular ejection fraction and left ventricular fractional shortening decreased in the control group. IVA improved cardiac performance. The expression of HCN4 and MiRP1 protein and the level of serum IL-1, IL-6, and TNF-α were decreased by IVA treatment. In conclusion, HCNs and the helper proteins were increased in the profile of myocardial inflammation. HCNs may be involved in the regulation of myocardial inflammation by inhibiting immune cell infiltration. Our findings can contribute to the development of IVA-based combination therapies for the future treatment of cardiac inflammation and heart failure.

Prediction of lymph node metastasis in patients with papillary thyroid cancer based on radiomics analysis and intraoperative frozen section analysis: A retrospective study.

INTRODUCTION: To evaluate the diagnostic efficiency among the clinical model, the radiomics model and the nomogram that combined radiomics features, frozen section (FS) analysis and clinical characteristics for the prediction of lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC). METHODS: A total of 208 patients were randomly divided into two groups randomly with a proportion of 7:3 for the training groups (n = 146) and the validation groups (n = 62). The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for the selection of radiomics features extracted from ultrasound (US) images. Univariate and multivariate logistic analyses were used to select predictors associated with the status of LN. The clinical model, radiomics model and nomogram were subsequently established by logistic regression machine learning. The area under the curve (AUC), sensitivity and specificity were used to evaluate the diagnostic performance of the different models. The Delong test was used to compare the AUC of the three models. RESULTS: Multivariate analysis indicated that age, size group, Adler grade, ACR score and the psammoma body group were independent predictors of lymph node metastasis (LNM). The results showed that in both the training and validation groups, the nomogram showed better performance than the clinical model, albeit not statistically significant (p > .05), and significantly outperformed the radiomics model (p < .05). However, the nomogram exhibits a slight improvement in sensitivity that could reduce the incidence of false negatives. CONCLUSION: We propose that the nomogram holds substantial promise as an effective tool for predicting LNM in patients with PTC.

Nanopore sequencing of full rRNA operon improves resolution in mycobiome analysis and reveals high diversity in both human gut and environments.

High-throughput sequencing has substantially improved our understanding of fungal diversity. However, the short read (<500 bp) length of current second-generation sequencing approaches provides limited taxonomic and phylogenetic resolution for species discrimination. Longer sequences containing more information are highly desired to provide greater taxonomic resolution. Here, we amplified full-length rRNA operons (~5.5 kb) and established a corresponding fungal rRNA operon database for ONT sequences (FRODO), which contains ONT sequences representing eight phyla, 41 classes, 109 orders, 256 families, 524 genera and 1116 species. We also benchmarked the optimal method for sequence classification and determined that the RDP classifier based on our FRODO database was capable of improving the classification of ONT reads, with an average of 98%-99% reads correctly classified at the genus or species level. We investigated the applicability of our approach in three representative mycobiomes, namely, the soil, marine and human gut mycobiomes, and found that the gut contains the largest number of unknown species (over 90%), followed by the marine (42%) and soil (33.8%) mycobiomes. We also observed a distinct difference in the composition of the marine and soil mycobiomes, with the highest richness and diversity detected in soils. Overall, our study provides a systematic approach for mycobiome studies and revealed that the previous methods might have underestimated the diversity of mycobiome species. Future application of this method will lead to a better understanding of the taxonomic and functional diversity of fungi in environmental and health-related mycobiomes.

Mechanism of lnRNA-ICL involved in lung cancer development in COPD patients through modulating microRNA-19-3p/NKRF/NF-κB axis.

The incidence of lung cancer (LC) in chronic obstructive pulmonary disease (COPD) patients is dozens of times higher than that in patients without COPD. Elevated activity of nuclear factor-k-gene binding (NF-κB) was found in lung tissue of patients with COPD, and the continuous activation of NF-κB is observed in both malignant transformation and tumor progression of LC, suggesting that NF-κB and its regulators may play a key role in the progression of LC in COPD patients. Here, we report for the first time that a key long non-coding RNA (lncRNA)-ICL involved in the regulation of NF-κB activity in LC tissues of COPD patients. The analyses showed that the expression of ICL significantly decreased in LC tissues of LC patients with COPD than that in LC tissues of LC patients without COPD. Functional experiments in vitro showed that exogenous ICL only significantly inhibited the proliferation, invasion and migration in primary tumor cells of LC patients with COPD compared to LC patients without COPD. Mechanism studies have shown that ICL could suppress the activation of NF-κB by blocking the hsa-miR19-3p/NKRF/NF-κB pathway as a microRNA sponge. Furthermore, In vivo experiments showed that exogenous ICL effectively inhibited the growth of patient-derived subcutaneous tumor xenografts (PDX) of LC patients with COPD and significantly prolonged the survival time of tumor-bearing mice. In a word, our study shows that the decrease of ICL is associated with an increased risk of LC in patients with COPD, ICL is not only expected to be a new therapeutic target for LC in COPD patients, but also has great potential to be used as a new marker for evaluating the occurrence, severity stratification and prognosis of LC in patients with COPD.

Magnetic resonance spectroscopy and liquid chromatography-mass spectrometry metabolomics study may differentiate pre-eclampsia from gestational hypertension.

OBJECTIVE: To investigate the findings of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and serum metabolomics for differentiating pre-eclampsia (PE) from gestational hypertension (GH). METHODS: This prospective study enrolled 176 subjects including a primary cohort with healthy non-pregnant women (HN, n = 35), healthy pregnant women (HP, n = 20), GH (n = 27), and PE (n = 39) and a validation cohort with HP (n = 22), GH (n = 22), and PE (n = 11). T1 signal intensity index (T1SI), apparent diffusion coefficient (ADC) value, and the metabolites on MRS were compared. The differentiating performances of single and combined MRI and MRS parameters for PE were evaluated. Serum liquid chromatography-mass spectrometry (LC-MS) metabolomics was investigated by sparse projection to latent structures discriminant analysis. RESULTS: Increased T1SI, lactate/creatine (Lac/Cr), and glutamine and glutamate (Glx)/Cr and decreased ADC value and myo-inositol (mI)/Cr in basal ganglia were found in PE patients. T1SI, ADC, Lac/Cr, Glx/Cr, and mI/Cr yielded an area under the curves (AUC) of 0.90, 0.80, 0.94, 0.96, and 0.94 in the primary cohort, and of 0.87, 0.81, 0.91, 0.84, and 0.83 in the validation cohort, respectively. A combination of Lac/Cr, Glx/Cr, and mI/Cr yielded the highest AUC of 0.98 in the primary cohort and 0.97 in the validation cohort. Serum metabolomics analysis showed 12 differential metabolites, which are involved in pyruvate metabolism, alanine metabolism, glycolysis, gluconeogenesis, and glutamate metabolism. CONCLUSIONS: MRS is expected to be a noninvasive and effective tool for monitoring GH patients to avoid the development of PE. KEY POINTS: • Increased T1SI and decreased ADC value in the basal ganglia were found in PE patients than in GH patients. • Increased Lac/Cr and Glx/Cr, and decreased mI/Cr in the basal ganglia were found in PE patients than in GH patients. • LC-MS metabolomics showed that the major differential metabolic pathways between PE and GH were pyruvate metabolism, alanine metabolism, glycolysis, gluconeogenesis, and glutamate metabolism.

Association of severity and prognosis with elevated blood pressure and heart rate levels in patients with intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) has a high mortality and morbidity in the world. Elevated blood pressure (BP) and heart rate (HR) have been identified as independent risk factors, with potential to predict prognosis and recurrence of cardiovascular diseases. Our study aimed to elucidate the association between BP and HR levels and the severity, as well as prognosis, of patients diagnosed with ICH. METHODS: The basic characteristics of patients and laboratory examination results, inclusive of BP and HR levels upon admission, were recorded as baseline data. The modified Rankin Scale and living status were taken into account for all patients at a 1-year follow-up. The relationship between various BP and HR levels and clinical outcome was analyzed using logistic regression and the Kaplan-Meier survival method. RESULTS: A total of 1,416 patients with acute ICH from 13 hospitals in Beijing were enrolled in our study. Logistic regression analysis indicated that patients with higher HR and BP (group 4), along with those with higher HR but lower BP (group 2), exhibited a poorer prognosis compared to those with lower BP and HR (group 1). This result was particularly pronounced in younger, male subgroups (OR (95% CI) = 4.379(2.946-6.508), P < 0.0001 for group 4; OR (95% CI) = 1.819 (1.219-2.714), P = 0.0034 for group 2). At the 1-year follow-up, group 4 patients demonstrated a significantly higher rate of fatal incidence compared to other groups (P < 0.01). CONCLUSIONS: Higher HR and BP levels, suggestive of an autonomic dysfunction, were independently associated with a poorer 1-year prognosis and reduced survival rate in ICH patients. Our findings underscore the need for early intervention to modulate these physiological parameters in patients with ICH.

Subarachnoid extension and unfavorable outcomes in patients with supratentorial intracerebral hemorrhage.

OBJECTIVE: Our study aimed to investigate the association between the subarachnoid extension of intracranial hemorrhage (SAHE) and clinical outcomes in patients with supratentorial intracerebral hemorrhage (ICH). METHODS: We analyzed the data from a prospective, multi-center, and registry-based database. Two experienced investigators independently assessed ICH imaging data. We compared baseline characteristics and follow-up outcomes. Multivariable logistic regression analysis was used to evaluate the association between SAHE and poor clinical outcomes. We also performed Kaplan-Meier curves and Cox proportional hazards regression analyses to analyze whether SAHE was relevant to a higher mortality rate. RESULTS: A total of 931 patients were included in this study (SAHE vs. no SAHE, 121 [13.0%] vs. 810 [87.0%]). Patients with SAHE had more severe neurological deficits, higher scores of the mRS, and more remarkable mortality rates at follow-up (all p values < 0.05). In multivariable-adjusted models, SAHE was independently associated with a higher risk of poor outcomes (adjusted OR [95%CI]: 2.030 [1.142-3.608] at 3 months; 2.348 [1.337-4.123] at 1 year). In addition, SAHE remained an independent association with an increased death rate at 1 year (adjusted HR [95%CI], 1.314[1.057-1.635]). In the subgroup analysis, the correlation between SAHE and prognosis exists in patients with lobar or deep ICH. CONCLUSIONS: SAHE is independently associated with poor outcomes in patients with supratentorial ICH. It may provide a promising target for developing new predictive tools targeting ICH.

Development and evaluation of a culturally adapted digital-platform integrated multifaceted intervention to promote the utilization of maternal healthcare services: a single-arm pilot study.

BACKGROUND: The utilization of hospital delivery and antenatal care (ANC) is essential for improving maternal and newborn outcomes. However, social and cultural barriers in underdeveloped rural areas hindered maternal care utilization. This study aims to design and evaluate the effectiveness of a culturally adapted digital-platform intervention to promote maternal care utilization among women in ethnic minority communities in China. METHODS: From January 1st, 2020, to December 31st, 2021, all pregnant women in Mianshan town, Liangshan Autonomous Prefecture, were invited to participate in the intervention. The multifaceted intervention included participatory and cultural-tailored health education on a popular social media platform, transportation subsidies, and capacity building and economic incentives for healthcare providers. The effectiveness of the intervention was evaluated by comparing two groups: mothers who gave live birth before the intervention (January 1st to December 31st, 2019) and mothers whose entire pregnancy period was covered by the intervention. The primary outcomes were the rate of hospital delivery and ANC utilization. Data on pregnant women were retrospectively collected through telephone surveys and the maternal and newborn's health monitoring system. RESULTS: A total of 237 intervention sample and 138 pre-intervention sample were included. The intervention group demonstrated significantly higher rates of hospital delivery (97.5% vs. 87.7%, p < 0.001), timely initiation of ANC (73.0% vs. 62.3%, p = 0.031), and timely completion of five-time ANC visits (37.1% vs.4.3%, p < 0.001) compared to the pre-intervention group. The intervention group was more likely to utilize hospital delivery (OR = 9.26, 95%CI [2.83-30.24], p < 0.001) and ANC, including timely initiation of ANC (OR = 2.18, 95%CI [1.31-3.62], p = 0.003), completion of five ANC visits (OR = 1.72, 95%CI [1.05-2.83], p = 0.032), and timely completion of five ANC visits (OR = 15.12, 95%CI [6.24-36.64], p < 0.001). CONCLUSIONS: The culturally adapted digital-platform integrated multifaceted intervention effectively promoted the utilization of hospital delivery, timely initiation of ANC, and completion of ANC visits in the Yi ethnic community in China. This study provides valuable insights for future interventions targeting maternal healthcare services in underdeveloped ethnic minority communities worldwide. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300073219. Registered 4 July 2023 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=199202 .

Systemic inflammation and immune index predicting outcomes in patients with intracerebral hemorrhage.

OBJECT: Recent evidence has suggested that systemic inflammatory and immune index (SIRI) and systematic inflammation index (SII) could predict prognosis in stroke patients. This study aimed to determine the effects of SIRI and SII on predicting in-hospital infections and unfavorable outcomes in patients with acute intracerebral hemorrhage (ICH). METHODS: We used the data from a prospective and registry-based study recruiting ICH patients between January 2014 and September 2016 in a single comprehensive stroke center. All patients were stratified by quartiles of SIRI or SII. Logistic regression analysis was used to estimate the associations with follow-up prognosis. The receiver operating characteristics (ROC) curves were performed to examine the predictive utility of these indexes for infections and prognosis. RESULTS: Six hundred and forty spontaneous ICH patients were enrolled in this study. Compared with the lowest quartile (Q1), SIRI or SII values both showed positive correlations with increased risks for poor 1-month outcomes (adjusted ORs in Q4 was 2.162 [95% CI: 1.240-3.772] for SIRI, 1.797 [95% CI: 1.052-3.070] for SII). Additionally, a higher level of SIRI, but not SII, was independently associated with a higher risk of infections and an unfavorable 3-month prognosis. The C-statistic for the combined SIRI and ICH score was higher than SIRI or ICH score alone for predicting in-hospital infections and poor outcomes. CONCLUSION: Elevated SIRI values were associated with in-hospital infections and poor functional outcomes. It may provide a new biomarker for ICH prognosis prediction, especially in the acute stage.

Ferrous sulfate reverses cerebral metabolic abnormality induced by minimal hepatic encephalopathy.

Orally administered ferrous iron was previously reported to significantly improve the cognition and locomotion of patients with minimal hepatic encephalopathy (MHE). However, the metabolic mechanisms of the therapeutic effect of ferrous iron are unknown. In this study, MHE was induced in rats by partial portal vein ligation (PPVL), and was treated with ferrous sulfate. The Morris water maze was used to evaluate the cognitive condition of the rats. The metabolites observed by NMR and validated by liquid chromatography-mass spectrometry were defined as the key affected metabolites. The enzyme activities and trace element contents in the rat brains were also investigated. The Mn content was found to be increased but the ferrous iron content decreased in the cortex and striatum in MHE. Decreased oxoglutarate dehydrogenase activity and increased glutamine synthetase (GS) and pyruvate carboxylase (PC) activity were observed in the cortex of MHE rats. Decreased pyruvate dehydrogenase activity and increased GS and PC activity were observed in the striatum of MHE rats. The levels of BCAAs and taurine were significantly decreased, and the contents of GABA, lactate, arginine, aspartate, carnosine, citrulline, cysteine, glutamate, glutamine, glycine, methionine, ornithine, proline, threonine and tyrosine were significantly increased. These metabolic abnormalities described above were restored after treatment with ferrous sulfate. Pathway enrichment analysis suggested that urea cycle, aspartate metabolism, arginine and proline metabolism, glycine and serine metabolism, and glutamate metabolism were the major metabolic abnormalities in MHE rats, but these processes could be restored and cognitive impairment could be improved by ferrous sulfate administration.

1α,25-dihydroxyvitamin D3 supplementation alleviates perfluorooctanesulfonate acid-induced reproductive injury in male mice: Modulation of Nrf2 mediated oxidative stress response.

Perfluorooctanesulfonate acid (PFOS) is a typical persistent organic pollutant that widely exists in the environment. To clarify the toxic effects and mechanisms of PFOS and to find effective intervention strategies have been attracted global attention. Here, we investigated the effects of PFOS on the male reproductive system and explored the potential protective role of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3 ). Our results showed that 1α,25(OH)2 D3 intervention significantly improved PFOS-induced sperm quality decline and testicular damage. Moreover, 1α,25(OH)2 D3 aggrandized the total antioxidant capacity. Furthermore, after PFOS exposure, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1, NQO1, and SOD2. Meanwhile, 1α,25(OH)2 D3 ameliorated PFOS-induced augment of Nrf2 and target genes. These findings indicated that 1α,25(OH)2 D3 might attenuate PFOS-induced reproductive injury in male mice via Nrf2-mediated oxidative stress.

Effectiveness of oncology nurse navigator on the incidence of postoperative pulmonary complications in gastric cancer patients undergoing radical gastrectomy.

BACKGROUND: Management of postoperative pulmonary complications (PPCs) can be challenging in gastric cancer patients undergoing radical gastrectomy and is always associated with poor prognosis. Even though oncology nurse navigator (ONN) provide effective and critical individualized care to patients, little is known about their impact on the occurrence of PPCs in gastric cancer patients. This study aimed to determine whether ONN decreases the incidence of PPCs in gastric cancer patients. METHODS: This was a retrospective review in which data for gastric cancer patients at one centre was evaluated before and after an ONN hired. An ONN was introduced to patients at their initial visit to manage pulmonary complications throughout treatment. The research was conducted from 1 August 2020 to 31 January 2022. The study participants were divided into the non-ONN group (from 1 August 2020 to 31 January 2021) and the ONN group (from 1 August 2021 to 31 January 2022). The incidence and severity of PPCs between the groups were then compared. RESULTS: ONN significantly decreased the incidence of PPCs (15.0% vs. 9.8%) (OR = 2.532(95% CI: 1.087-3.378, P = 0.045)), but there was no significant difference in the components of PPCs including pleural effusion, atelectasis, respiratory infection, and pneumothorax. The severity of PPCs was also significantly higher in the non-ONN group (p = 0.020). No significant statistical difference was observed for the major pulmonary complications ([Formula: see text] 3) between the two groups (p = 0.286). CONCLUSIONS: Role of ONN significantly decrease the incidence of PPCs in gastric cancer patients undergoing radical gastrectomy.