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Abstract Background Hepatitis B remains a significant global health concern with widespread communicability. Nevertheless, data on its burden and trends in children and adolescents were limited. We aim to evaluate the global, regional, and national trends of total burden related to hepatitis B in children and adolescents aged 0–19 years from 1990 to 2021. Methods The age-standardized incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated by the Global Burden of Disease (GBD) study from 1990 to 2021. These indicators were stratified by sex, age, socio-demographic index (SDI), and disease stage. We calculated the correlation between them and SDI. The temporal trends were examined using the annual average percentage change (AAPC) and joinpoint regression. Results The global age-standardized incidence of hepatitis B in children and adolescents decreased from 1385.20 per 100,000 population in 1990 to 418.68 per 100,000 population in 2021, with an AAPC of -3.76%. Similarly, age-standardized DALYs decreased from 70.78 per 100,000 population to 36.31 per 100,000 population, with an AAPC of -2.13%. The age-standardized prevalence (AAPC − 3.53%) and mortality (AAPC − 2.09%) of hepatitis B also decreased significantly. From 1990 to 2021, the age-standardized incidence and prevalence among males exhibited a higher trend compared to females, although both declined over time. These two indicators also decreased across all age subgroups, with consistently higher rates observed in the 15–19 age group compared to other age groups. The burden of hepatitis B demonstrated a notable reduction in countries with high-middle SDI, while it was highest in countries with low SDI. In 2021, Central sub-Saharan Africa and West sub-Saharan Africa reported the highest age-standardized incidence. For age-standardized DALYs, South Asia was the only region to experience an increase (AAPC 1.09%), while East Asia showed the largest decline (AAPC − 7.58%). Alcohol and drug use remained important risk factors for DALYs among people aged 15–19 years. Furthermore, the impact of drug use on disease burden was increasing, particularly in high-SDI countries. Conclusions The global burden and trends of hepatitis B decreased significantly in children and adolescents, exhibiting regional and national variations. Management of alcohol and drug use remains a major challenge for people aged 15–19 years.

Objectives: This study aimed to survey the geriatric nursing competencies of clinical nursing staff in Chongqing City, China, and provide suggestions to enhance these competencies. Methods: This study was conducted in 204 hospitals in Southwest China from December 24, 2022 to January 7, 2023. The “Geriatric Nursing Competence of Clinical Nurse Investigation Tool” was used to explore factors that influence geriatric nurses’ competencies via stratified sampling. The survey was conducted by distributing and collecting questionnaires through the online platform Wenjuanxing. Results: A total of 10,692 nurses answered the questionnaires. Of these questionnaires, 9,442 were valid. The total geriatric nursing competence score of the clinical nursing staff was 2.29 ± 0.81, the secondary hospital score was 2.23 ± 0.78, and the tertiary hospital’s overall mean score was 2.33 ± 0.83. The factors that influenced secondary hospitals included the department of medicine, age of nurses and total length of career (P

Abstract Abdominal aortic aneurysms (AAA) are a significant health concern in developed countries due to their considerable mortality rate. The crucial factor of the progression of AAA is the release of neutrophils and neutrophil extracellular traps (NETs). Magnetic particle imaging (MPI) is a new imaging technique that offers the capability to detect superparamagnetic iron oxide nanoparticles (SPION) with exceptional sensitivity. We aimed to investigate the functional imaging of MPI for the detection and monitoring of neutrophil infiltration within AAA. A novel multimodal imaging agent targeting neutrophils, PEG-Fe3O4-Ly6G–Cy7 nanoparticles (Ly6G NPs), were designed by coupling Fe3O4 nanoparticles with Ly6G antibodies and Cy7. The targeting and sensitivity of Ly6G NPs were assessed using MPI and fluorescence imaging (FLI) in the AAA mouse model. After the inhibition of NETosis, the degree of neutrophil infiltration and AAA severity were assessed using MPI with Ly6G NPs. Ly6G NPs accurately localized and quantitatively analyzed AAA lesion sites in mice using MPI/FLI/CT. Compared to the control group, elevated MPI and FLI signal intensities were detected at the abdominal aortic lesion site, and neutrophil infiltration and NETs accumulation were detected by histological analysis in the AAA models. After the inhibition of NETs accumulation in vivo, pathological damage in the abdominal aorta was significantly reduced, along with a decrease in the accumulation of Ly6G NPs and MPI signals. This multimodal MPI strategy revealed that nanoparticles targeting Ly6G can be used to detect neutrophil infiltration within AAA and monitor AAA severity.

Abstract Human enteroviruses are highly prevalent world-wide. Up to more than 100 subtypes of enteroviruses can cause several diseases, including encephalitis, meningitis, myocarditis, hand-foot-mouth disease, conjunctivitis, respiratory diseases, and gastrointestinal diseases, thus posing a great threat to human health. This study aimed to investigate the epidemiological characteristics of enterovirus in children in Hangzhou, China before and after the COVID-19 outbreak. Systematic monitoring of enterovirus infections was performed by collecting samples from the children admitted to the inpatient wards and outpatient departments in the Children’s Hospital, Zhejiang University School of Medicine, between January 2019 and May 2023. A commercial real-time RT PCR kit was utilized to detect enteroviruses. Among the 34,152 samples collected, 1162 samples, accounting for 3.4% of the samples, were tested positive for enteroviruses. The annual positive rates of the enteroviruses were 5.46%, 1.15%, 4.43%, 1.62%, and 1.96% in 2019, 2020, 2021, 2022, and May 2023, respectively. The positivity rate of the enteroviruses was highest among children aged 3–5 years and 5–7 years. Moreover, the monthly positivity rate of enterovirus infection ranged from 0.32% to 10.38%, with a peak in June and July. Serotypes, especially EV71 and CA16, causing severe symptoms such as HFMD, were decreasing, while the proportion of unidentified serotypes was on the rise. The incidence of enteroviruses in Hangzhou was higher in children aged 1–3 years and 7–18 years.

Abstract Background Pseudomonas juntendi is a newly identified opportunistic pathogen, of which we have limited understanding. P. juntendi strains are often multidrug resistant, which complicates clinical management of infection. Methods A strain of Pseudomonas juntendi (strain L4326) isolated from feces was characterized by MALDI-TOF-MS and Average Nucleotide Identity BLAST. This strain was further subject to whole-genome sequencing and Maximum Likelihood phylogenetic analysis. The strain was phenotypically characterized by antimicrobial susceptibility testing and conjugation assays. Results We have isolated the novel P. juntendi strain L4236, which was multidrug resistant, but retained sensitivity to amikacin. L4236 harbored a megaplasmid that encoded bla OXA−1 and a novel bla IMP−1 resistance gene variant. P. juntendi strain L4236 was phylogenetically related to P. juntendi strain SAMN30525517. Conclusion A rare P. juntendi strain was isolated from human feces in southern China with a megaplasmid coharboring bla IMP−1−like and bla OXA−1. Antimicrobial selection pressures may have driven acquisition of drug-resistance gene mutations and carriage of the megaplasmid.

BackgroundBile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks.MethodsIn this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology.Results(1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets.ConclusionThis study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids.

Purpose: Leptin resistance represents a primary pathological manifestation in obesity. Investigating potential treatments and associated mechanisms to restore leptin sensitivity is crucial for effective obesity management. This study aimed to explore the therapeutic potential of acupoints catgut embedding (ACE) in addressing obesity and its associated leptin resistance. Methods: A simple obesity model was established by subjecting C57 male mice to a high-fat diet (HFD) for 12 weeks, followed by ACE treatment administered to half of the obese mice for a duration of 4 weeks. The levels of leptin and its receptor-lepRb, were assessed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. Autophagy progression markers were evaluated through quantitative polymerase chain reaction (qPCR) and Western blot analysis. Also, the liver autophagosomes were photographed using electron microscopy. The role of autophagy in regulating leptin resistance was elucidated using an autophagy suppression model. Results: Comparative analyses demonstrated that ACE treatment resulted in a significant reduction in body weight and blood lipid levels compared to the HFD group. Furthermore, serum leptin levels decreased, while liver lepRb expression increased following ACE treatment. The mRNA and protein expression levels of autophagy in liver were adjusted by ACE treatment. Interestingly, the beneficial effects of ACE were attenuated upon the administration of an autophagy inhibitor. Additionally, ACE treatment led to the activation of the AMPK-mTOR signaling pathway, a crucial regulator of autophagy. Conclusion: These findings suggest that ACE therapy holds promise for recovering leptin resistance by enhancing autophagy progression, mediated via the AMPK-mTOR signaling pathway in liver.

Background: The immune microenvironment and oxidative stress of melanoma show significant heterogeneity, which affects tumor growth, invasion and treatment response. Single-cell and bulk RNA-seq data were used to explore the heterogeneity of the immune microenvironment and oxidative stress of melanoma. Methods: The R package Seurat facilitated the analysis of the single-cell dataset, while Harmony, another R package, was employed for batch effect correction. Cell types were classified using Uniform Manifold Approximation and Projection (UMAP). The Secreted Signaling algorithm from CellChatDB.human was applied to elucidate cell-to-cell communication patterns within the single-cell data. Consensus clustering analysis for the skin cutaneous melanoma (SKCM) samples was executed with the R package ConsensusClusterPlus. To quantify immune infiltrating cells, we utilized CIBERSORT, ESTIMATE, and TIMERxCell algorithms provided by the R package Immuno-Oncology Biological Research (IOBR). Single nucleotide variant (SNV) analysis was conducted using Maftools, an R package specifically designed for this purpose. Subsequently, the expression levels of PXDN and PAPSS2 genes were assessed in melanoma tissues compared to adjacent normal tissues. Furthermore, in vitro experiments were conducted to evaluate the proliferation and reactive oxygen species expression in melanoma cells following transfection with siRNA targeting PXDN and PAPSS2. Results: Malignant tumor cell populations were reclassified based on a comprehensive single-cell dataset analysis, which yielded six distinct tumor subsets. The specific marker genes identified for these subgroups were then used to interrogate the Cancer Genome Atlas Skin Cutaneous Melanoma (TCGA-SKCM) cohort, derived from bulk RNA sequencing data, resulting in the delineation of two immune molecular subtypes. Notably, patients within the cluster2 (C2) subtype exhibited a significantly more favorable prognosis compared to those in the cluster1 (C1) subtype. An alignment of immune characteristics was observed between the C2 subtype and unique immune functional tumor cell subsets. Genes differentially expressed across these subtypes were subsequently leveraged to construct a predictive risk model. In vitro investigations further revealed elevated expression levels of PXDN and PAPSS2 in melanoma tissue samples. Functional assays indicated that modulation of PXDN and PAPSS2 expression could influence the production of reactive oxygen species (ROS) and the proliferative capacity of melanoma cells. Conclusion: The constructed six-gene signature can be used as an immune response and an oxidative stress marker to guide the clinical diagnosis and treatment of melanoma.

The human multidrug transporter P-glycoprotein (P-gp) is physiologically essential and of key relevance to biomedicine. Recent structural studies have shed light on the mode of inhibition of the third-generation inhibitors for human P-gp, but the molecular mechanism by which these inhibitors enter the transmembrane sites remains poorly understood. In this study, we utilized all-atom molecular dynamics (MD) simulations to characterize human P-gp dynamics under a potent inhibitor, tariquidar, bound condition, as well as the atomic-level binding pathways in an explicit membrane/water environment. Extensive unbiased simulations show that human P-gp remains relatively stable in tariquidar-free and bound states, while exhibiting a high dynamic binding mode at either the drug-binding pocket or the regulatory site. Free energy estimations by partial nudged elastic band (PNEB) simulations and Molecular Mechanics Generalized Born Surface Area (MM/GBSA) method identify two energetically favorable binding pathways originating from the cytoplasmic gate with an extended tariquidar conformation. Interestingly, free tariquidar in the lipid membrane predominantly adopts extended conformations similar to those observed at the regulatory site. These results suggest that membrane lipids may preconfigure tariquidar into an active ligand conformation for efficient binding to the regulatory site. However, due to its conformational plasticity, tariquidar ultimately moves toward the drug-binding pocket in both pathways, explaining how it acts as a substrate at low concentrations. Our molecular findings propose a membrane-assisted mechanism for the access and binding of the third-generation inhibitors to the binding sites of human P-gp, and offer deeper insights into the molecule design of more potent inhibitors against P-gp-mediated drug resistance.

Abstract Background The association of glycemic variability with severe consciousness disturbance and in-hospital all-cause mortality in critically ill patients with cerebrovascular disease (CVD) remains unclear, This study aimed to investigate the association of glycemic variability with cognitive impairment and in-hospital death. Method We extracted all blood glucose measurements of patients diagnosed with CVD from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Glycemic variability was defined as the coefficient of variation (CV), which was determined using the ratio of standard deviation and the mean blood glucose levels. Cox hazard regression models were applied to analyze the link between glycemic variability and outcomes. We also analyzed non-linear relationship between outcome indicators and glycemic variability using restricted cubic spline curves. Results The present study included 2967 patients diagnosed with cerebral infarction and 1842 patients diagnosed with non-traumatic cerebral hemorrhage. Log-transformed CV was significantly related to cognitive impairment and in-hospital mortality, as determined by Cox regression. Increasing log-transformed CV was approximately linearly with the risk of cognitive impairment and in-hospital mortality. Conclusion High glycemic variability was found to be an independent risk factor for severe cognitive decline and in-hospital mortality in critically ill patients with CVD. Our study indicated that enhancing stability of glycemic variability may reduced adverse outcomes in patients with severe CVD.

Abstract Background and aims There are no clear conclusions as to whether heart failure (HF) and coronary heart disease (CAD) increase the risk of erectile dysfunction (ED).In our study, we used Mendelian randomization (MR) analysis to discover a causal relationship between HF, CAD and ED. Methods Single nucleotide polymorphisms (SNPs) associated with HF, CAD and ED were obtained from the MRC IEU Open Genome-Wide Association Study (GWAS) database.After a series of screenings, the remaining SNPs were selected as instrumental variables (IVs) for HF and CAD for MR analysis to assess the relationship between genetically predicted HF or CAD and the pathogenesis of ED.Among them, we used the random-effects inverse variance weighted (IVW) method as the primary analysis method.Finally, Cochran’s q-test, funnel plots, MR-Egger regression, Leave-one-out method and MR-PRESSO were used for sensitivity analysis. Results In the IVW method, there was no significant causal relationship between genetically predicted HF and CAD and the incidence of ED.(HF: OR = 1.17, 95% CI 0.99–1.39; p = 0.074;CAD: OR = 1.08, 95% CI 0.99–1.17, p = 0.068)。The results of sensitivity analyses supported our conclusion that no horizontal pleiotropism was found. Conclusion This study did not find a causal relationship between HF or CAD and ED in European populations, which requires further in-depth research.

Artificial intelligence generated content technology is reshaping the production and consumption patterns of digital content.The research was based on the basic concepts and technological development process of artificial intelligence generated content technology, focusing on exploring ethical risks and governance challenges such as privacy leakage, algorithm hegemony, digital divide, intellectual property protection and employment impact caused by artificial intelligence generated content.After reviewing the typical governance paths and experiences of developed countries abroad, this paper summarized and proposed measures and development suggestions for China to address the potential risks of AI generated content.One was to prioritize development and coordinate layout; Second was to strengthen the full factor investment in the research and development of artificial intelligence technology; Third was to improve the governance rule system of artificial intelligence technology; Fourth was to accelerate the research and development of artificial intelligence governance technology.

Abstract Background The emergence and wide spread of carbapenemase-producing Enterobacteriaceae (CPE) poses a growing threat to global public health. However, clinically derived carbapenemase-producing Citrobacter causing multiple infections has rarely been investigated. Here we first report the isolation and comparative genomics of two bla NDM-5 carrying Citrobacter freundii (C. freundii) isolates from a patient with bloodstream and urinary tract infections. Results Antimicrobial susceptibility testing showed that both bla NDM-5 carrying C. freundii isolates were multidrug-resistant. Positive modified carbapenem inactivation method (mCIM) and EDTA-carbapenem inactivation method (eCIM) results suggested metallo-carbapenemase production. PCR and sequencing confirmed that both metallo-carbapenemase producers were bla NDM-5 positive. Genotyping and comparative genomics analyses revealed that both isolates exhibited a high level of genetic similarity. Plasmid analysis confirmed that the bla NDM-5 resistance gene is located on IncX3 plasmid with a length of 46,161 bp, and could successfully be transferred to the recipient Escherichia coli EC600 strain. A conserved structure sequence (ISAba125-IS5-bla NDM-5-trpF-IS26-umuD-ISKox3) was found in the upstream and downstream of the bla NDM-5 gene. Conclusions The data presented in this study showed that the conjugative bla NDM-5 plasmid possesses a certain ability to horizontal transfer. The dissemination of NDM-5-producing C. freundii isolates should be of close concern in future clinical surveillance. To our knowledge, this is the first study to characterize C. freundii strains carrying the bla NDM-5 gene from one single patient with multiple infections.

Abstract Objective To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML). Methods We used R software to conduct a meta-analysis of prospective clinical trials of IDH inhibitors in the treatment of IDH-mutated AML published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to November 15th, 2022. Results A total of 1109 IDH-mutated AML patients from 10 articles (11 cohorts) were included in our meta-analysis. The CR rate, ORR rate, 2-year survival (OS) rate and 2-year event-free survival (EFS) rate of newly diagnosed IDH-mutated AML (715 patients) were 47%, 65%, 45% and 29%, respectively. The CR rate, ORR rate, 2-year OS rate, median OS and median EFS of relapsed or refractory (R/R) IDH-mutated AML (394 patients) were 21%, 40%, 15%, 8.21 months and 4.73 months, respectively. Gastrointestinal adverse events were the most frequently occurring all-grade adverse events and hematologic adverse events were the most frequently occurring ≥ grade 3 adverse events. Conclusion IDH inhibitor is a promising treatment for R/R AML patients with IDH mutations. For patients with newly diagnosed IDH-mutated AML, IDH inhibitors may not be optimal therapeutic agents due to low CR rates. The safety of IDH inhibitors is controllable, but physicians should always pay attention to and manage the differentiation syndrome adverse events caused by IDH inhibitors. The above conclusions need more large samples and high-quality RCTs in the future to verify.

Objective To investigate BRCA1 / 2 gene mutations and their relationship with clinicopathological features in patients with breast cancer in Zhoushan Islands. Methods High-throughput whole-exome gene sequencing was used to detect BRCA1 / 2 mutations in 776 breast cancer patients in Zhoushan Islands. Results The BRCA1 / 2 mutation rate of breast cancer patients in Zhoushan Islands was 4.38% (34/776). BRCA1 mutations were significantly correlated with age, molecular type, and family history of breast and ovarian cancers. BRCA2 mutations were most commonly found in invasive lobular carcinoma. Moreover, the BRCA2 mutation rate of cancers with molecular type luminal B (receptor protein–tyrosine kinase [HER2]-negative) was also relatively high. Conclusion The rate of BRCA1 / 2 mutations in breast cancer patients from Zhoushan Islands is approximately 4.38%, and BRCA1 mutation is related to age, molecular type, and family history of breast and ovarian cancers.

Background Diabetes and diabetes complications are on the rise in US adults aged

Chemotherapy leads to significant side effects in patients, especially in the gut, resulting in various clinical manifestations and enhanced economic pressure. Until now, many of the underlying mechanisms remain poorly understood. Here, we used Drosophila melanogaster (fruit fly) as in vivo model to delineate the side effects and underlying mechanisms of Irinotecan (CPT-11). The results showed that administration of CPT-11 delayed larval development, induced imbalance of male to female ratio in offspring, shortened lifespan, impaired locomotor ability, changed metabolic capacity, induced ovarian atrophy, and increased excretion. Further, CPT-11 supplementation dramatically caused intestinal damages, including decreased intestinal length, increased crop size, disrupted gastrointestinal acid-based homeostasis, induced epithelial cell death, and damaged the ultrastructure and mitochondria structure of epithelial cells. The cross-comparative analysis between transcriptome and bioinformation results showed that CPT-11 induced intestinal damage mainly via regulating the Toll-like receptor signaling, NF-kappa B signaling, MAPK signaling, FoxO signaling, and PI3K-AKT signaling pathways. In addition, CPT-11 led to the intestinal damage by increasing ROS accumulation. These observations raise the prospects of using Drosophila as a model for the rapid and systemic evaluation of chemotherapy-induced side effects and high-throughput screening of the protective drugs.

Abstract Background and objectives Phenotypic switching in vascular smooth muscle cells (VSMCs) has been linked to aortic aneurysm, but the phenotypic landscape in aortic aneurysm is poorly understood. The present study aimed to analyse the phenotypic landscape, phenotypic differentiation trajectory, and potential functions of various VSMCs phenotypes in aortic aneurysm. Methods Single-cell sequencing data of 12 aortic aneurysm samples and 5 normal aorta samples (obtained from GSE166676 and GSE155468) were integrated by the R package Harmony. VSMCs were identified according to the expression levels of ACTA2 and MYH11. VSMCs clustering was determined by the R package ‘Seurat’. Cell annotation was determined by the R package ‘singleR’ and background knowledge of VSMCs phenotypic switching. The secretion of collagen, proteinases, and chemokines by each VSMCs phenotype was assessed. Cell‒cell junctions and cell–matrix junctions were also scored by examining the expression of adhesion genes. Trajectory analysis was performed by the R package ‘Monocle2’. qPCR was used to quantify VSMCs markers. RNA fluorescence in situ hybridization (RNA FISH) was performed to determine the spatial localization of vital VSMCs phenotypes in aortic aneurysms. Results A total of 7150 VSMCs were categorize into 6 phenotypes: contractile VSMCs, fibroblast-like VSMCs, T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs. The proportions of T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs were significantly increased in aortic aneurysm. Fibroblast-like VSMCs secreted abundant amounts of collagens. T-cell-like VSMCs and macrophage-like VSMCs were characterized by high chemokine levels and proinflammatory effects. Adipocyte-like VSMCs and mesenchymal-like VSMCs were associated with high proteinase levels. RNA FISH validated the presence of T-cell-like VSMCs and macrophage-like VSMCs in the tunica media and the presence of mesenchymal-like VSMCs in the tunica media and tunica adventitia. Conclusion A variety of VSMCs phenotypes are involved in the formation of aortic aneurysm. T-cell-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs play pivotal roles in this process. Video Abstract

In order to investigate effects of fatty acid unsaturation on the gel properties of myosin, four kinds of fatty acids (stearic acid, oleic acid, linoleic acid, and α-linolenic acid) with different saturation was added into hairtail myosin. The changes of gel strength, water holding capacity, chemical forces, rheological properties, gel electrophoresis and protein secondary structure of myosin were analyzed. The results showed that gel strength and water holding capacity of myosin increased first and then decreased with the increasing of fatty acid unsaturation. The gel strength and water holding capacity of myosin-linoleic acid composite system were the highest, increasing by 59.73% and 15.73% compared with control group, respectively. The results of the rheological and electropherogram indicated that the storage modulus (G') and loss modulus (G'') of myosin containing fatty acids were higher than that of control group. The G' and G'' increased first and then decreased with the increasing of fatty acid unsaturation, and reached the maximum value in the myosin-linoleic acid group. However, there was no significant change in protein composition among all the groups. Infrared spectroscopy showed that the unsaturation of fatty acid had no obvious effect on the molecular backbone of myosin, but stearic acid, oleic acid, and linoleic acid promoted the conformation transform of myosin to irregular direction. In summary, fatty acid unsaturation had a significant effect on the gel properties of myosin, and linoleic acid was the best at improving the gel properties of hairtail myosin.

Abstract Background To determine the efficacy of hyperbaric oxygen therapy (HBO) in the treatment of necrotizing soft tissue infections (NSTI), we conducted a meta-analysis of the available evidence. Methods Data sources were PubMed, Embase, Web of Science, Cochrane Library, and reference lists. The study included observational trials that compared HBO with non-HBO, or standard care. The primary outcome was the mortality rate. Secondary outcomes were the number of debridement, amputation rate and complication rate. Relative risks or standardized mean differences with 95% confidence intervals were calculated for dichotomous and continuous outcomes, respectively. Results A total of retrospective cohort and case-control studies were included, including 49,152 patients, 1448 who received HBO and 47,704 in control. The mortality rate in the HBO group was significantly lower than that in the non-HBO group [RR = 0.522, 95% CI (0.403, 0.677), p 0.05]. In terms of complications, the incidence of MODS was lower in the HBO group than in the non-HBO group [RR = 0.205, 95% CI (0.164, 0.256), p 0.05). Conclusion The current evidence suggests that the use of HBO in the treatment of NSTI can significantly reduce the mortality rates and the incidence rates of complications. However, due to the retrospective nature of the studies, the evidence is weak, and further research is needed to establish its efficacy. It is also important to note that HBO is not available in all hospitals, and its use should be carefully considered based on the patient's individual circumstances. Additionally, it is still worthwhile to stress the significance of promptly evaluating surgical risks to prevent missing the optimal treatment time.

Geological movements can affect carbon distribution patterns and turnover mechanisms in terrestrial ecosystems by altering surface landscape patterns. However, little is known about how changes in surface landscape features after geological hazards affect the microecological mechanisms of soil carbon. In this study, eight landslides with similar standing conditions and formation times but different scales were selected in the geologically active zone of Southwest China. A macro genome sequencing approach was used to study the microbial changes in the soil carbon functions of landslides after earthquakes. The results indicated that the scale of landslide scale was a significant factor affecting soil carbon stocks after earthquake. Among the landslide scale factors, landslide width had a greater effect on soil carbon storage than length or area. Landslide width corresponded with increased microbial decomposition of plant (lignin, hemicellulose) and fungal (chitin) carbon sources, but both chitinous soil content and its decomposition function gene abundance were low and had a small effect on the total carbon pool. The major bacterial phyla (Actinobacteria, Candidatus Rokubacteria, and Acidobacteria) mineralize carbon sources from plant and fungal biomass fractions through their selective adaptation mechanisms based on the landslide scale. Starch and polysaccharide related metabolic pathways differed significantly between landslides at different scales. Overall, our results emphasize the importance of microbes in surface carbon dynamics driven by geological movements. It is also noted that the scale of landscape degradation following geological disturbance is a key indicator that soil carbon and that microbes influence postdisaster soil carbon recovery and accumulation by regulating their selection and utilization of plant-derived carbon. The findings of this study help to estimate the turnover and distribution of terrestrial ecosystem carbon driven by geological movements at a larger scale.

Objective: The objective of this research was to assess the level and determinants of medical personnel's knowledge, attitudes, and practices regarding the management of sexual health in breast cancer survivors residing in western China. Background: Sexual well-being is a crucial aspect of one's overall satisfaction with life. Once female sexual dysfunction (FSD) occurs, it will affect patients' satisfaction and life quality seriously. In all healthcare settings, the management of sexual health relies heavily on the vital contribution of medical personnel. Nevertheless, the sexual requirements of individuals with breast cancer are still partially unmet. Design: A web-based questionnaire was used to conduct a multi-centered, cross-sectional study involving medical staff from 26 hospitals in nine cities of Guizhou Province, China. Methods: Data was gathered from healthcare professionals using a validated tool, the knowledge, attitudes, practices assessment scale for managing the sexual health of breast cancer patients in medical staff. This tool was used to evaluate the knowledge, attitudes, and practices of medical staff regarding sexual health management. Results: In this study, a grand total of 3181 healthcare professionals took part. The overall KAP scores, including knowledge, attitudes, and practices, were 47.15 ± 11.91, 72.55 ± 12.56, and 58.61 ± 11.45, respectively. Three variables exhibited a strong and favorable correlation. The study identified significant concerns regarding the limited understanding of medical personnel regarding effective strategies for enhancing sexual health function in breast cancer patients, as well as their diminished confidence in addressing FSD. The scores of knowledge, attitudes, and practices related to sexual health management were significantly influenced by whether or not training was received. Conclusions: The study results emphasize the importance of adopting a holistic approach to enhance the understanding, perspectives, and behaviors of healthcare professionals regarding the management of sexual health. In addition to enhancing the standard of care for individuals with breast cancer.

Objectives: This study aimed to determine the incidence of falls and risk factors associated with falling in discharged older adults. Methods: A prospective study was conducted on older adults who had been issued a discharge order in a Class A tertiary hospital in Chongqing, China, from May 2019 to August 2020. The risk of falling, depression, frailty, and daily activities were evaluated at discharge using the mandarin version of the fall risk self-assessment scale, Patient Health Questionnaire-9 (PHQ-9), FRAIL scale, and Barthel Index, respectively. The cumulative incidence function estimated the cumulative incidence of falls in older adults after discharge. And the risk factors of falls were explored using the sub-distribution hazard function in the competing risk model. Results: In a total of 1,077 participants, the total cumulative incidence of falls at 1, 6 and 12 months after discharge was 4.45%, 9.03%, and 10.80%, respectively. The cumulative incidence of falls in older adults with depression (26.19%, 49.93%, and 58.53%, respectively) and those with physical frailty (21.59%, 41.67%, and 48.73%, respectively) was much higher than that in those without depression and physical frailty (P

Abstract Objective To analyze the incidence and risk of hypertension associated with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in cancer patients and provide reference for clinicians. Methods We used R software to conduct a meta-analysis of phase II/III randomized controlled trials (RCT) on PARP inhibitors for cancer treatment published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to July 29th, 2022. Results We included 32 RCTs with 10,654 participants for this meta-analysis. For total PARP inhibitors, the incidence and risk ratio of all-grade hypertension were 12% and 1.22 (95% CI: 0.91–1.65, P = 0.19, I2 = 81%), and the incidence and risk ratio of grade 3–4 hypertension were 4% and 1.24 (95% CI: 0.74–2.08, P = 0.42, I2 = 68%). Compared with the control group, the niraparib group, olaparib 800 mg/day group, and olaparib plus cediranib group increased the risk of any grade and grade 3–4 hypertension, while the veliparib group and rucaparib group did not increase the risk of any grade and grade 3–4 hypertension, and olaparib 200 mg-600 mg/day group (exclude olaparib plus cediranib regime) reduced the risk of any grade and grade 3–4 hypertension. Conclusion Olaparib 200-600 mg/day (excluding olaparib plus cediranib regimen) may be the most suitable PARP inhibitor for cancer patients with high risk of hypertension, followed by veliparib and rucaparib. Niraparib, olaparib 800 mg/day and olaparib combined with cediranib may increase the risk of developing hypertension in cancer patients, clinicians should strengthen the monitoring of blood pressure in cancer patients and give medication in severe cases.

Abstract Background Insomnia and poor sleep quality are highly prevalent conditions related to coronavirus disease 2019 (COVID-19) complications among clinical nurses. Although cognitive behavioral therapy for insomnia (CBT-I) is a first-line treatment, CBT-I suffers from several major drawbacks. This study investigates whether the application of the internet-delivered mindfulness-based stress reduction (iMBSR) intervention will produce effects that are non-inferior to the internet-delivered CBT-I (iCBT-I) intervention in reducing the severity of insomnia in clinical nurses with insomnia at the end of the study. Methods This study protocol presents an internet-delivered, parallel-groups, assessor-blinded, two-arm, non-inferiority randomized controlled trial. The primary outcome is sleep quality, assessed by the Insomnia Severity Index. Secondary outcomes include depression, dysfunctional beliefs, five facets of mindfulness, and client satisfaction. Conclusion It is expected that this study may address several gaps in the literature. The non-inferiority study design is a novel approach to evaluating whether a standardized, complementary treatment (i.e., MBSR) is as practical as a gold standard treatment rather than its potential benefits. This approach may lead to expanded evidence-based practice and improve patient access to effective treatments. Trial registration Trial registration number: ISRCTN36198096 . Registered on 24th May 2022.

Abstract Background Gastric cancer has a high incidence and mortality rate. Angiogenesis is necessary for tumor infiltration and metastasis and affects patient prognosis. YKL-39 has monocyte chemotactic activity and pro-angiogenic activity in some tumors. In this study, we investigated the relationship between YKL-39 and tumor-associated macrophages and microangiogenesis in gastric cancer to determine its potential as a prognostic biomarker. Materials and methods A total of 119 patients with gastric cancer who had undergone gastrectomy at the 940th Hospital of the Joint Security Force between 2014 and 2018 were included in this study. We assayed the protein expression of YKL-39, CD68, and CD34 by immunohistochemistry in tissues of 119 patients with gastric cancer, as well as the intracellular expression of YKL-39 and CD68 by immunofluorescence. Data were analyzed with SPSS Statistics 25.0 to explore the impact of expression of YKL-39, CD68, and CD34 in gastric cancer patients and the relationship among them. Results Our results show that YKL-39 was expressed in both the nucleus and cytoplasm of gastric cancer cells and tumor mesenchyme. YKL-39 protein expression was associated with the depth of tumor infiltration, lymph node metastasis, and TNM stage; CD68 protein expression was associated with lymph node metastasis and TNM stage; CD34 protein expression was not associated with clinicopathological characteristics. Expression of YKL-39 was positively correlated with CD68 and CD34 (p

Abstract A decade ago, an online survey resulted in the “Protecting Cantonese Movement” (PCM) in Guangzhou, Guangdong Province, China, around which some articles were produced. Based on the bibliometric analysis of data retrieved from the China National Knowledge Infrastructure (CNKI), the Web of Science, and Google Scholar keyword searches during 2010 and 2021, this paper reviews the PCM literature to summarize its major features and general trends. It reveals that the published journals or newspaper articles focus on interpretating PCM, analyzing its causes from sociocultural, sociolinguistic, socioeconomic and media environmental perspectives, and proposing countermeasures and suggestions at political, ideological and sociolinguistic environmental levels. It concludes that PCM is of far-reaching significance to the continuous research ranging from Cantonese preserving, promotion of Mandarin, language planning, language policy, and language conflict to language ecology.

BackgroundStudies have shown that deaf individuals distribute more attention to the peripheral visual field and exhibit enhanced visual processing for peripheral stimuli relative to hearing individuals. This leads to better detection of peripheral target motion and simple static stimuli in hearing individuals. However, when threatening faces that represent dangerous signals appear as non-targets in the periphery, it remains unclear whether deaf individuals would retain an advantage over hearing individuals in detecting them.MethodsIn this study, 23 deaf and 28 hearing college students were included. A modified perceptual load paradigm and event-related potentials (ERPs) were adopted. In the task, participants were instructed to search for a target letter in a central letter array, while task-irrelevant face distractors (happy, neutral, and angry faces) were simultaneously presented in the periphery while the central perceptual load was manipulated.ResultsBehavioral data showed that angry faces slowed deaf participants' responses to the target while facilitating the responses of hearing participants. At the electrophysiological level, we found modulation of P1 amplitude by central load only in hearing individuals. Interestingly, larger interference from angry face distractors was associated with higher P1 differential amplitude only in deaf individuals. Additionally, the amplitude of N170 for happy face distractors was smaller than that for angry and neutral face distractors in deaf participants.ConclusionThe present data demonstrates that, despite being under central perceptual load, deaf individuals exhibit less attentional inhibition to peripheral, goal-irrelevant angry faces than hearing individuals. The result may reflect a compensatory mechanism in which, in the absence of auditory alertness to danger, the detection of visually threatening information outside of the current attentional focus has a high priority.

Nanotheranostic agents capable of simultaneously enabling real-time tracking and precise treatment at tumor sites play an increasingly pivotal role in the field of medicine. In this article, we report a novel near-infrared-II window (NIR-II) emitting downconversion rare-earth nanoparticles (RENPs) to improve image-guided therapy for breast cancer. The developed α-NaErF4@NaYF4 nanoparticles (α-Er NPs) have a diameter of approximately 24.1 nm and exhibit superior biocompatibility and negligible toxicity. RENPs exhibit superior imaging quality and photothermal conversion efficiency in the NIR-II range compared to clinically approved indocyanine green (ICG). Under 808 nm laser irradiation, the α-Er NPs achieve significant tumor imaging performance and photothermal effects in vivo in a mouse model of breast cancer. Simultaneously, it combines X-ray computed tomography (CT) and ultrasound (US) tri-modal imaging to guide therapy for cancer. The integration of NIR-II imaging technology and RENPs establishes a promising foundation for future medical applications.

Objectives The aim of this study was to investigate the level of practice of peripherally inserted central catheter (PICC) maintenance among nurses in Guizhou province, China, and to explore its influencing factors.Design Cross-sectional study.Setting 11 tertiary and 26 secondary hospitals of Guizhou province, China.Participants A total of 832 nurses engaged in clinical work of PICC maintenance participated in the present study.Primary outcome measures PICC maintenance knowledge questionnaire, PICC maintenance attitude questionnaire and PICC maintenance practice questionnaire were administrated online for measuring participants’ knowledge, attitude and practice of PICC maintenance, respectively.Results The mean score of nurses’ practice of PICC maintenance was 79.77±12.13 and 60.8% of participants reported acceptable practices of PICC maintenance. The availability of PICC guidelines (β=0.10, p=0.002), previous training on PICC maintenance (β=0.18, p

BackgroundFeather pecking (FP) is a maladaptive behavior in laying hens that is associated with numerous physiological traits, including those involving the central neurotransmitter system and the immune system, which have been identified in many species as being regulated by the gut microbiota via the “microbiota-gut-brain” (MGB) axis. Yet, it is unknown whether and how gut microbiota influences FP by regulating multiple central neurotransmission systems and immune system.MethodsThis study was measured the prevalence of severe FP (SFP) in the commercial layer farm. The chicken flock with the highest frequency of SFP were selected for FP phenotype identification. Nontargeted metabolomics was performed to investigated the differences in the peripheral and central metabolites and 16S rDNA sequencing was performed to investigated the differences in gut microbiome of laying hens with different FP phenotypes. Correlation analysis was performed to determine the potential mechanism by which the disturbed gut microbiota may modulate host physiology and behavior.ResultsThe results showed that pullets (12 weeks of age) showed significantly higher SFP frequencies than chicks (6 weeks of age) and adults (22 weeks of age; p

In the realm of daily activity planning, precise weather forecasting services hold paramount significance. However, the prevalent dissemination of weather forecasts through conventional channels like radio, television, and the internet often yields only generalized regional predictions. This limitation contributes to diminished forecast reach, inadequate accuracy, and a lack of individualization, thwarting the effective distribution of meteorological insights and inhibiting the fulfillment of personalized forecast demands. Addressing these concerns, our study proposes a personalized weather forecasting approach that harnesses machine learning techniques and leverages the 5G messaging platform. By amalgamating projected user travel data, we augment personalized weather reports and extend user coverage to achieve tailored, timely, and high-quality weather services. Concretely, our research commences with an extensive analysis of large-scale user travel behavior data to extract pertinent travel attributes. Subsequently, we construct a user’s future location prediction model—dubbed the Loc-PredModel—by employing the Extreme Gradient Boosting (XGBoost) algorithm to forecast users’ trip destinations and arrival times. Anchored in the anticipated outcomes of user travel behavior, personalized weather data reports are formulated. Experimental results underscore the Loc-PredModel’s remarkable predictive prowess, demonstrating a root mean squared error (RMSE) value of 0.208 and a coefficient of determination (R2) value of 0.935, affirming its efficacy in prognosticating users’ trip destinations and arrival times. Furthermore, our 5G message-driven platform, rooted in intelligent personalized meteorological services, underwent testing within Chengdu city and garnered positive user feedback. Our research effectively surmounts the limitations of conventional weather forecasting platforms by furnishing users with more precise and customized weather information predicated on behavioral analysis and the 5G information ecosystem. This study not only advances the theoretical groundwork of intelligent meteorology but also offers invaluable insights and guidance for future advancement. By providing users with a more personalized and timely intelligent meteorological service experience, our approach exhibits transferability, with the research methodology and model potentially extendable nationwide or even on a larger scale beyond the study’s Chengdu-based scope.

Abstract Background Invasive candidal infection combined with bacterial bloodstream infection is one of the common nosocomial infections that is also the main cause of morbidity and mortality. The incidence of invasive Candidal infection with bacterial bloodstream infection is increasing year by year worldwide, but data on China is still limited. Methods We included 246 hospitalised patients who had invasive candidal infection combined with a bacterial bloodstream infection from January 2013 to January 2018; we collected and analysed the relevant epidemiological information and used machine learning methods to find prognostic factors related to death (training set and test set were randomly allocated at a ratio of 7:3). Results Of the 246 patients with invasive candidal infection complicated with a bacterial bloodstream infection, the median age was 63 years (53.25–74), of which 159 (64.6%) were male, 109 (44.3%) were elderly patients (> 65 years), 238 (96.7%) were hospitalised for more than 10 days, 168 (68.3%) were admitted to ICU during hospitalisation, and most patients had records of multiple admissions within 2 years (167/246, 67.9%). The most common blood index was hypoproteinemia (169/246, 68.7%), and the most common inducement was urinary catheter use (210/246, 85.4%). Moreover, the most frequently infected fungi and bacteria were Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis by machine learning method are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, C-Reactive protein (CRP), leukocyte count, neutrophil count, Procalcitonin (PCT), and total bilirubin level. Conclusion Our results showed that the most common candida and bacteria infections were caused by Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, CRP, leukocyte count, neutrophil count, PCT and total bilirubin level.

Co-infection of RNA viruses may contribute to their recombination and cause severe clinical symptoms. However, the tracking and identification of SARS-CoV-2 co-infection persist as challenges. Due to the lack of methods for detecting co-infected samples in a large amount of deep sequencing data, the lineage composition, spatial–temporal distribution, and frequency of SARS-CoV-2 co-infection events in the population remains unclear. Here, we propose a hypergeometric distribution–based method named Cov2Coinfect with the ability to decode the lineage composition from 50,809 deep sequencing data. By resolving the mutational patterns in each sample, Cov2Coinfect can precisely determine the co-infected SARS-CoV-2 variants from deep sequencing data. Results from two independent and parallel projects in the United States achieved a similar co-infection rate of 0.3–0.5 % in SARS-CoV-2 positive samples. Notably, all co-infected variants were highly consistent with the co-circulating SARS-CoV-2 lineages in the regional epidemiology, demonstrating that the co-circulation of different variants is an essential prerequisite for co-infection. Overall, our study not only provides a robust method to identify the co-infected SARS-CoV-2 variants from sequencing samples, but also highlights the urgent need to pay more attention to co-infected patients for better disease prevention and control.

Machine game is a kind of artificial intelligence in which machines imitate the way people think and make decisions.It is currently the most challenging research direction in the field of artificial intelligence, whose research status largely represents the development level of artificial intelligence.The basic concepts, research status and typical applications of machine game were summarized, its challenges and development trends were discussed, and the possible applications of machine game on the social governance were analyzed.Then, a social cognitive parallel game method based on the parallel systems and the machine game were proposed, aiming at providing new ideas for the research of social governance.

Abstract Background To study the competency of general practitioners (GPs) in Shanghai, China on prevention and management of type 2 diabetes, also understand factors that may prohibit it. Methods A survey questionnaire with 25 questions was designed based on 2013 Chinese Type 2 Diabetes Prevention Guidelines and Chinese Type 2 Diabetes Prevention Guidelines (Grassroots Edition) and conducted among 789 GPs who work at 54 community healthcare centers (CHCs) within 16 districts at Shanghai, China. Excel 2016 and SPSS 24.0 were used for data analysis, and a difference of P

ObjectiveTo study the incidence and distribution of adverse events in immune checkpoint inhibitors (ICI) for digestive system cancers and to provide a reference for the safe, rational, and effective use of immune detection site inhibitors.MethodsWe searched for articles published in English between January 1, 2010, and May 18, 2022. All clinical trials of ICI-based therapies for digestive system cancers were investigated, including only randomized controlled trials that reported data on the overall incidence of treatment-related adverse events (trAEs) or immune-related adverse reactions (irAEs) or tables.ResultsWe searched 2048 records, of which 21 studies (7108 patients) were eligible for inclusion. The incidence of ICI trAEs of any grade was 82.7% (95% CI 73.9-90.0), and the incidence of grade 3 or higher trAEs was 27.5% (95% CI 21.3-34.1). The pooled rate of ICI irAEs of any grade was 26.3% (95% CI 11.8-44.0), and the incidence of grade 3 or higher irAEs was 9.4% (95% CI 1.1-24.6). In multivariate analysis, the incidence, characteristics, and distribution of AEs varied by cancer type, combination therapy modality (single/two-drug), and different agent types.ConclusionOur meta-analysis summarizes AEs associated with ICI in digestive system cancers. The incidence, characteristics, and distribution of AEs vary by cancer type, combination therapy modality, and different agent types. These findings can be considered for the early identification of AEs and provide effective interventions to reduce the severity of these patients. It can provide a clinical reference and may contribute to clinical practice.

BackgroundNilotinib, which inhibits cellular Abelson tyrosine kinase, may be an effective treatment for patients with Parkinson's disease (PD). The purpose of this study is to evaluate the outcomes of different doses of nilotinib in patients with PD.MethodsWe searched PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Clinical Trials from inception to 7 March 2022 to identify all randomized controlled trials (RCTs) of nilotinib reporting outcomes of interest in patients with PD. Outcomes included tolerability, efficacy, safety, and CSF biomarker levels. Review manager 5.4 software was used to analyze all data.ResultsThree RCTs with a total of 163 patients were included. No significant difference was found between 150 mg nilotinib or 300 mg nilotinib and placebo in terms of tolerability, adverse events, or HVA levels. 300 mg nilotinib showed significantly higher Movement Disorder Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) scores [SMD = 0.52, 95%CI = (0.12, 0.92), P = 0.01] and 3,4-dihydroxyphenylacetic acid (DOPAC) levels [SMD = 0.52, 95%CI = (0.12, 0.92), P = 0.01], and lower α-synuclein levels [SMD = −2.16, 95%CI = (−3.38, −1.84), P < 0.00001] compared with placebo. And compared with 150 mg nilotinib, 300 mg nilotinib showed significantly lower α-synuclein levels [SMD = −1.16, 95%CI = (−1.70, −0.61), P < 0.0001].ConclusionsAlthough our study demonstrated favorable tolerability and safety of different doses of nilotinib, and improvement in part of CSF biomarker levels of 300 mg nilotinib, the poor efficacy on motor outcomes indicated that nilotinib had no advantages in the clinic.

Remote ischemic preconditioning (RIPC) may improve exercise performance. However, the influence of RIPC on aerobic performance and underlying physiological mechanisms during hypobaric hypoxia (HH) exposure remains relatively uncertain. Here, we systematically evaluated the potential performance benefits and underlying mechanisms of RIPC during HH exposure. Seventy-nine healthy participants were randomly assigned to receive sham intervention or RIPC (4 × 5 min occlusion 180 mm Hg/reperfusion 0 mm Hg, bilaterally on the upper arms) for 8 consecutive days in phases 1 (24 participants) and phase 2 (55 participants). In the phases 1, we measured the change in maximal oxygen uptake capacity (VO2max) and muscle oxygenation (SmO2) on the leg during a graded exercise test. We also measured regional cerebral oxygenation (rSO2) on the forehead. These measures and physiological variables, such as cardiovascular hemodynamic parameters and heart rate variability index, were used to evaluate the intervention effect of RIPC on the changes in bodily functions caused by HH exposure. In the phase 2, plasma protein mass spectrometry was then performed after RIPC intervention, and the results were further evaluated using ELISA tests to assess possible mechanisms. The results suggested that RIPC intervention improved VO2max (11.29%) and accelerated both the maximum (18.13%) and minimum (53%) values of SmO2 and rSO2 (6.88%) compared to sham intervention in hypobaric hypoxia exposure. Cardiovascular hemodynamic parameters (SV, SVRI, PPV% and SpMet%) and the heart rate variability index (Mean RR, Mean HR, RMSSD, pNN50, Lfnu, Hfnu, SD1, SD2/SD1, ApEn, SampEn, DFA1and DFA2) were evaluated. Protein sequence analysis showed 42 unregulated and six downregulated proteins in the plasma of the RIPC group compared to the sham group after HH exposure. Three proteins, thymosin β4 (Tβ4), heat shock protein-70 (HSP70), and heat shock protein-90 (HSP90), were significantly altered in the plasma of the RIPC group before and after HH exposure. Our data demonstrated that in acute HH exposure, RIPC mitigates the decline in VO2max and regional oxygenation, as well as physiological variables, such as cardiovascular hemodynamic parameters and the heart rate variability index, by influencing plasma Tβ4, HSP70, and HSP90. These data suggest that RIPC may be beneficial for acute HH exposure.

COVID-19 has affected millions of people around the globe. People's mental health, especially those of nurses, has been primarily affected by the fear of this virus. More focus has been paid to vaccination and treatment of the virus, but less attestation has been given to addressing the mental health of people affected by the virus. Empirical studies show that different external factors are not easily manageable and controllable by the individual. This study preliminarily explores the connection between fear of COVID-19 and secondary traumatic stress in nurses. Further, it examines the moderating effects of occupational self-efficacy on the relationship between fear of COVID-19 and secondary traumatic stress. Data for the study was collected from the nurses of six large hospitals in Karachi, Pakistan. The final analysis was performed on 243 samples. Studies on COVID-19 suggest that increased occupational self-efficacy decreases fear and its impact. This study offers insights for managers to develop stress management programs and provide proper training and counseling sessions to the nurses to motivate them emotionally. Theoretically, this study broadens the understanding of the theory of emotions by using the pandemic as a stressor. Future studies may explore different roles of occupational self-efficacy and study its influential role in managing different kinds of emotions explained by the theory of emotions. Managers at the workplace could design different self-efficacy training for nurses to increase their self-motivation to fight different types of stress they face at the workplace.

To better understand and control the crystallization of different polymorphs, a comprehensive crystal structure analysis was conducted by using fluralaner as a model compound, and the thermodynamic stability, phase transformation, and selective nucleation mechanisms were studied. Various analytical techniques such as powder X-ray diffraction, thermal analysis, and FT-IR spectra were used to comprehensively characterize Form I, Form Ⅱ, and Form III of fluralaner, and it was found that there is structural similarity between Form I and Form III, which was further confirmed by single crystal X-ray diffraction. However, it was found that Form Ⅱ had unique molecular conformation and packing pattern. The lattice energy was calculated by Materials Studio 7.0 and the thermodynamic stability of three forms was explored by phase transformation experiments, which suggested that the order of thermodynamic stability was Form Ⅱ > Form I > Form III. The selective nucleation of Form I and Form III with similar structure was studied through FT-IR spectra and molecular dynamics simulations. The results indicated that the addition of n-hexane may hinder the solute–solute interaction in the solution, thus resulting in the nucleation of different polymorphs.

Abstract Background Hypoxia, which affects the development, metastasis and prognosis of cancer, represents a key feature of cancer. This study describe a hypoxia risk factor model, with predicting the prognosis of cervical cancer. Methods Based on hypoxia pathway related genes, we divided cervical cancer samples into high and low expression groups. A cox analysis was then performed. Genes from these cervical cancer samples showing a significant impact on OS were selected for cluster analysis to obtain two subtypes. The TPM dataset of TCGA was divided into training and validation sets. For the training set, a lasso analysis was conducted as based on cox analysis of meaningful genes and a risk factor model was constructed. The constructed model was verified in internal and external data sets. Finally, RT-PCR, immunohistochemistry were used to detect the expression of relative genes or proteins and functional assays were used to evaluate the biological function of signature genes. Results Two molecular subtypes were obtained, Cluster2 vs Cluster1.These subtypes were obtained by clustering with a total of 149 DEGs (Differential expressed genes) being in line with this standard, of which 27 were up-regulated and 122 were down-regulated. The five genes with lambda = 0.0571 were selected to construct the model, the RiskScore = AK4*0.042 + HK2*0.021 + P4HA1*0.22 + TGFBI*0.1 + VEGFA*0.077. Further, in order to verify the signature, we used TCGA-test and GSE44001 chip datasets to test, and finally got a good risk prediction effect in those datasets. Moreover, the result of RT-PCR and immunohistochemistry demonstrated that AK4, HK2, P4HA1, TGFBI and VEGFA were all highly expressed in these cervical cancer tissue samples. The functional study shown that expression of AK4, HK2, P4HA1, TGFBI and VEGFA can regulate the proliferation, migration, and invasion ability of cervical cancer cells in vitro. Conclusions In summary, we developed a 5-gene signature prognostic hierarchical system based on the hypoxic pathway of cervical cancer, which is independent of clinical characteristics. And also conducted experimental verifications on these signature gene. Therefore, we propose that use of this classifier as a molecular diagnostic test can provide an effective means for evaluating the prognostic risk of cervical cancer patients, and provide potential targets for the treatment of cervical cancer patients.

It is suggested that remote ischemic preconditioning (RIPC) may be a promising treatment for improving healthy adults’ cognitive control. However, direct empirical evidence was absent. Therefore, this study aims to provide evidence for the impact of RIPC on cognitive control. Sixty healthy young male volunteers were recruited, and 30 of them received 1-week RIPC treatment (RIPC group), while the rest did not receive RIPC (control group). Their cognitive control before and after RIPC treatment was evaluated using the classic Stroop task, and the scalp electricity activity was recorded by event-related potentials (ERPs). The behavioral results showed a conventional Stroop interference effect of both reaction times (RTs) and the accuracy rate (ACC), but the Stroop interference effect of RTs significantly decreased in the posttest compared to the pretest. Furthermore, at the electrophysiological level, ERP data showed that N450 and SP for incongruent trials were larger than that for congruent trials. Importantly, the SP differential amplitude increased after RIPC treatment, whereas there was no significant change in the control group. These results implied that RIPC treatment could improve cognitive control, especially conflict resolving in the Stroop task.

Bacteraemia has attracted great attention owing to its serious outcomes, including deterioration of the primary disease, infection, severe sepsis, overwhelming septic shock or even death. Candidemia, secondary to bacteraemia, is frequently seen in hospitalised patients, especially in those with weak immune systems, and may lead to lethal outcomes and a poor prognosis. Moreover, higher morbidity and mortality associated with candidemia. Owing to the complexity of patient conditions, the occurrence of candidemia is increasing. Candidemia-related studies are relatively challenging. Because candidemia is associated with increasing mortality related to invasive infection of organs, its pathogenesis warrants further investigation. We collected the relevant clinical data of 367 patients with concomitant candidemia and bacteraemia in the first hospital of China Medical University from January 2013 to January 2018. We analysed the available information and attempted to obtain the undisclosed information. Subsequently, we used machine learning to screen for regulators such as prognostic factors related to death. Of the 367 patients, 231 (62.9%) were men, and the median age of all patients was 61 years old (range, 52–71 years), with 133 (36.2%) patients aged >65 years. In addition, 249 patients had hypoproteinaemia, and 169 patients were admitted to the intensive care unit (ICU) during hospitalisation. The most common fungi and bacteria associated with tumour development and Candida infection were Candida parapsilosis and Acinetobacter baumannii, respectively. We used machine learning to screen for death-related prognostic factors in patients with candidemia and bacteraemia mainly based on integrated information. The results showed that serum creatinine level, endotoxic shock, length of stay in ICU, age, leukocyte count, total parenteral nutrition, total bilirubin level, length of stay in the hospital, PCT level and lymphocyte count were identified as the main prognostic factors. These findings will greatly help clinicians treat patients with candidemia and bacteraemia.

Flexible CZTSSe solar cells have attracted much attention due to their earth-abundant elements, high stability, and wide application prospects. However, the environmental problems caused by the high toxicity of the Cd in the buffer layers restrict the development of flexible CZTSSe solar cells. Herein, we develop a Cd-free flexible CZTSSe/ZnO solar cell. The influences of the ZnO films on device performances are investigated. The light absorption capacity of flexible CZTSSe solar cells is enhanced due to the removal of the CdS layer. The optimal thickness of the ZnO buffer layers and the appropriate annealing temperature of the CZTSSe/ZnO are 100 nm and 200 °C. Ultimately, the optimum flexible CZTSSe/ZnO device achieves an efficiency of 5.0%, which is the highest efficiency for flexible CZTSSe/ZnO solar cells. The systematic characterizations indicate that the flexible CZTSSe/ZnO solar cells based on the optimal conditions achieved quality heterojunction, low defect density and better charge transfer capability. This work provides a new strategy for the development of the environmentally friendly and low-cost flexible CZTSSe solar cells.

ObjectiveTo investigate the effects of sport stacking on the overall cognition and brain function in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI).MethodsA single-blind randomized controlled design was performed using sport stacking for 30 min, 5 days/week for 12 weeks. Forty-eight subjects with mild AD or MCI were randomly divided into the sport stacking group (T-mAD = 12, T-MCI = 12) and the active control group (C-mAD = 11, C-MCI = 13). Auditory Verbal Learning Test (AVLT), Alzheimer's Disease Cooperative Study–Activities of Daily Living scale (ADCS-ADL), Geriatric Depression Scale (GDS-30), and Pittsburgh Sleep Quality Index (PSQI) were performed, the level of amyloid β-protein-40 (Aβ-40), Aβ-42, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1(IGF-1), tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and soluble trigger receptor expressed on myeloid cells 2 (sTREM2) in plasma were tested, and brain functional connectivity in resting state and activation under finger movement task were analyzed by functional near-infrared spectroscopy (fNIRS).ResultsThirty-nine patients completed the trial. After 4 weeks, we found a significant increase in AVLT score in T-MCI (6.36 ± 5.08 vs. −1.11 ± 4.23, p = 0.004), and T-mAD group (4.60 ± 4.77 vs. −0.11 ± 2.89, p = 0.039). After 12 weeks, there was a significantly improved in AVLT (9.64 ± 4.90 vs. −0.33 ± 6.10, p = 0.002) and ADCS-ADL (3.36 ± 3.59 vs. −1.89 ± 2.71, p = 0.003) in T-MCI. There was a significant improvement in AVLT (5.30 ± 5.42 vs. 0.44 ± 2.40) in T-mAD (p < 0.05). Plasma levels of BDNF were upregulated in both T-MCI and T-mAD, and IGF-1 increased in T-MCI (P < 0.05) compared to the control groups. The functional connectivity in MCI patients between DLPFC.R and SCA.R, SMA.L, and SCA.R was decreased. In contrast, in mAD patients, the brain regional function connection was increased between DLPFC.R and Broca's.L. The activation of channel 36 located in the left primary somatosensory cortex was significantly increased after 12-week training, which was correlated with the improved AVLT and the increase of BDNF.ConclusionOur findings suggested that sport stacking is effective for patients with MCI and mild AD, possibly through increasing the expression of neuroprotective growth factors and enhancing neural plasticity to improve neurocognitive performance.Clinical Trial Registrationhttps://www.ClinicalTrials.gov, ChiCTR.org.cn, identifier: ChiCTR-2100045980.