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Abstract Background The connection between lipid-related obesity indices and severe headache or migraine in young and middle-aged people aged 20–60 remains ambiguous, and there are gaps in the discriminative ability of different indicators for severe headaches or migraines. Consequently, we set out to look into this association utilizing National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004. Methods After the values of waist-to-height ratio (WHtR), body-mass index (BMI), body roundness index (BRI), visceral adiposity index (VAI), lipid accumulation product (LAP), triglyceride glucose index (TyG), cardiac metabolism index (CMI), waist triglyceride Index (WTI), conicity index (CI) and weight-adjusted waist index (WWI) were estimated, with minimal sufficient adjustment for confounders determined by directed acyclic graph (DAG), weighted univariable and multivariable logistic regression analyses were carried out to ascertain the relationship between them and migraine. Stratified analysis and cross-effect analysis were implemented to examine the variability of intergroup correlations. Restricted cubic splines (RCS) and receiver operating characteristic (ROC) were then employed to examine nonliner relationships and its discriminatory ability for severe headache or migraine, respectively. Results 3354 United States adults were involved in our study, of whom 839 (25.01%) had severe headache or migraine. After adjusting for relevant covariables, WHtR, BRI, BMI, LAP, WTI and VAI were all associated with migraine and WHtR (OR = 6.38, 95% CI: 2.25,18.09, P 0.05). Conclusions Among those ten lipid-related obesity indicators evaluated in the study, WHtR, BMI and BRI demonstrated linear positive dose-response relationships with the prevalence of migraine in young and middle-aged individuals within the United States and WHtR showed the best predictive ability. Our study can provide important insight into epidemiological research and comprehensive management of obese patients with migraine.

Abstract Objective This study aims to investigate the influence of social determinants of health (SDoH) on cognitive performance. Methods This study surveyed a sample of older adults aged 60 years and older from the 2011–2014 cohort of participants in the U.S. National Health and Nutrition Examination Survey (NHANES). Data were collected during each survey cycle on self-reported domains of SDoH, which included eight subscales: employment, family income-to-poverty ratio, food security, education level, health insurance coverage, type of health insurance, home ownership, and marital status. Cognitive performance was evaluated using three tests: the Digit Symbol Substitution Test (DSST) for processing speed, the Animal Fluency Test (AFT) for executive function, and a subtest from the Coalition to Establish an Alzheimer’s Disease Registry (CERAD) for memory. Multifactorial linear regression modeling was employed to explore the association between SDoH and cognitive performance. Results A total of 2,819 elderly subjects were included in this study for analysis, with a mean age of 69.14 ± 0.19 years, 54.36% female and 45.64% male. The study found a negative association between the accumulation of unfavorable SDoH factors and cognitive performance. Similarly, certain unfavorable SDoH domains were negatively associated with cognitive performance. Conclusion The findings suggest that unfavorable SDoH domains, particularly when unfavorable SDoH factors accumulate, are linked to decreased cognitive performance. Actively investigating the relationship between these factors may be a crucial strategy for delaying dementia onset.

Abstract The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profile the immunogenicity of AR-MPXV5, a penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates. Immunization with two doses of AR-MPXV5 to cynomolgus macaques effectively elicits antibody responses and cellular responses. Importantly, based on the challenge model with a contemporary MPXV clade II strain, AR-MPXV5 demonstrates effective efficacy in preventing skin lesions, eliminating viremia and reducing viral loads in multiple tissues after challenge in naive male animals. More importantly, AR-MPXV5 is well-tolerated in stable chronic SIV-infected rhesus monkeys, while eliciting comparable MPXV-specific humoral and cellular responses in both naive and SIV-infected monkeys. Together, these results support further clinical development of the AR-MPXV5 vaccine.

Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressing, life-threatening syndrome characterized by excessive immune activation, often presenting as a complex cytokine storm. This hyperactive immune response can lead to multi-organ failure and systemic damage, resulting in an extremely short survival period if left untreated. Over the past decades, although HLH has garnered increasing attention from researchers, there have been few advancements in its treatment. The cytokine storm plays a crucial role in the treatment of HLH. Investigating the detailed mechanisms behind cytokine storms offers insights into targeted therapeutic approaches, potentially aiding in early intervention and improving the clinical outcome of HLH patients. To date, there is only one targeted therapy, emapalumab targeting interferon-γ, that has gained approval for primary HLH. This review aims to summarize the current treatment advances, emerging targeted therapeutics and underlying mechanisms of HLH, highlighting its newly discovered targets potentially involved in cytokine storms, which are expected to drive the development of novel treatments and offer fresh perspectives for future studies. Besides, multi-targeted combination therapy may be essential for disease control, but further trials are required to determine the optimal treatment mode for HLH.

Abstract Background Colony stimulating factor 1 (CSF1) is generally expressed by immune cells in response to pro-inflammatory stimuli. The CSF1 receptor (CSFR) is activated by CSF1, and plays a key role in macrophage homeostasis. Furthermore, the CSF1R+ macrophages maintain homeostasis in the intestinal epithelium. The aim of this study was to explore the functions of CSF1-expressing and CSF1R+ macrophages in necrotizing enterocolitis (NEC), which commonly affects the ileum of neonates. Methods In-situ CSF1 expression in the intestines of neonates with NEC or intestinal atresia (n = 4 each) was detected by immunofluorescence staining. The CSF1 levels in the intestinal crypt-derived organoid cultures were measured by ELISA. Peripheral blood monocyte-derived Mφ macrophages were co-cultured with the organoids and stimulated with lipopolysaccharide (LPS) to mimic the inflamed state of the ileum in NEC patients. Results CSF1 was expressed in the intestinal epithelial cells of the fetal and neonatal samples, but suppressed in the NEC samples. Furthermore, CSF1 expression was downregulated in the intestinal crypt-derived organoids by LPS. CSF1R+ macrophages were detected near the intestinal crypts in the non-inflamed intestines but were absent in tissues obtained from pediatric NEC patients. Peripheral blood monocyte-derived macrophages promoted intestinal organoid proliferation in vitro following CSF1 stimulation. Finally, low concentrations of LPS slightly enhanced the proliferation of organoids co-cultured with the macrophages, whereas higher doses had a significant inhibitory effect. Conclusions Intestinal epithelial cells express CSF1 to regulate the resident macrophages, maintain epithelial homeostasis, and resist infection. The abundant CSF1R+ macrophages in the fetal intestine may overexpress TNF-α upon activation of the TLR4/NF-κB pathway, resulting in epithelial damage and NEC induction.

Abstract Nitrous acid (HONO), a key precursor of hydroxyl radicals (OH), is one of the factors affecting atmospheric chemistry and air quality. Currently, the proposed sources of HONO are not able to fully explain observed HONO concentrations. In this study, a comprehensive field observation of HONO was conducted in the autumn of 2021 in urban Beijing. The box model using a default Master Chemical Mechanism (MCM) was unable to reproduce the observed HONO concentrations with a normalized mean bias (NMB) of −92.8%. The NMB improved to −46.1% after the inclusion of seven additional HONO formation pathways. Several factors like vehicle emission factor (1.23%) and nocturnal NO2 heterogeneous uptake coefficient on the ground surface (8.25 × 10−6) were calculated based on observational data. The enhancement factor for nocturnal NO2 heterogeneous conversion was established as a function of relative humidity (RH) and incorporated into the model, which compensated for the missing nocturnal HONO sources and well-reproduced the observed HONO concentrations, with an NMB of −5.1%. The major source of HONO at night was found to be the heterogeneous reaction of NO2 on the ground surface, contributing up to 85.6%. During the daytime, it was the homogeneous reaction of NO with OH, accounting for 41.8%. The daytime primary source of OH was mainly the photolysis of HONO, which constituted 73.6% and therefore promoted the formation of secondary pollutants and exacerbated haze events.

Chlorophyll is an important nutrient in celery and one of the main indexes of quality evaluation. RNA editing in chloroplasts is an important factor affecting chloroplast development and chlorophyll biosynthesis. Multisite organelle RNA editing factor (MORF) protein is a necessary regulator of chloroplast RNA editing. In this study, a total of 8 MORF genes in celery were identified, which were named AgMORF1a, AgMORF1b, AgMORF2a, AgMORF2b, AgMORF3, AgMORF7, AgMORF8 and AgMORF9 according to their subfamily classification. The physicochemical property, conserved motifs, cis-acting elements and protein interaction were predicted according to the sequences. The phylogenetic relationships and evolutionary selective pressure between MORF genes in celery and other Apiaceae plants were further analyzed. The results showed that AgMORF1b, AgMORF2a, AgMORF2b and AgMORF9 were predicted to be localized in chloroplasts. The evolution of MORF genes in 4 Apiaceae plants including celery, carrot, coriander and water dropwort was influenced by purify selection. Transcriptome data showed that the transcriptional levels of AgMORF2a, AgMORF2b, AgMORF8 and AgMORF9 were relatively higher among all MORF genes in petioles of celery, indicating their major role. RT-qPCR data showed that the expression levels of the above 4 genes were significantly higher in petioles of green celery than those of white celery. This study provided a basis for analyzing the effects of MORF proteins on chloroplast development of celery with different chlorophyll accumulation.

Background To construct and evaluate a predictive model for in-hospital mortality among critically ill patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT), based on nine machine learning (ML) algorithm.Methods The study retrospectively included patients with AKI who underwent CRRT during their initial hospitalization in the United States using the medical information mart for intensive care (MIMIC) database IV (version 2.0), as well as in the intensive care unit (ICU) of Huzhou Central Hospital. Patients from the MIMIC database were used as the training cohort to construct the models (from 2008 to 2019, n = 1068). Patients from Huzhou Central Hospital were utilized as the external validation cohort to evaluate the models (from June 2019 to December 2022, n = 327). In the training cohort, least absolute shrinkage and selection operator (LASSO) regression with cross-validation was employed to select features for constructing the model and subsequently established nine ML predictive models. The performance of these nine models on the external validation cohort dataset was comprehensively evaluated based on the area under the receiver operating characteristic curve (AUROC) and the optimal model was selected. A static nomogram and a web-based dynamic nomogram were presented, with a comprehensive evaluation from the perspectives of discrimination (AUROC), calibration (calibration curve) and clinical practicability (DCA curves).Results Finally, 1395 eligible patients were enrolled, including 1068 patients in the training cohort and 327 patients in the external validation cohort. In the training cohort, LASSO regression with cross-validation was employed to select features and nine models were individually constructed. Compared to the other eight models, the Lasso regularized logistic regression (Lasso-LR) model exhibited the highest AUROC (0.756) and the optimal calibration curve. The DCA curve suggested a certain clinical utility in predicting in-hospital mortality among critically ill patients with AKI undergoing CRRT. Consequently, the Lasso-LR model was the optimal model and it was visualized as a common nomogram (static nomogram) and a web-based dynamic nomogram (https://chsyh2006.shinyapps.io/dynnomapp/). Discrimination, calibration and DCA curves were employed to assess the performance of the nomogram. The AUROC for the training and external validation cohorts in the nomogram model was 0.771 (95%CI: 0.743, 0.799) and 0.756 (95%CI: 0.702, 0.809), respectively. The calibration slope and Brier score for the training cohort were 1.000 and 0.195, while for the external validation cohort, they were 0.849 and 0.197, respectively. The DCA indicated that the model had a certain clinical application value.Conclusions Our study selected the optimal model and visualized it as a static and dynamic nomogram integrating clinical predictors, so that clinicians can personalized predict the in-hospital outcome of critically ill patients with AKI undergoing CRRT upon ICU admission.

In order to study the flow blending and transporting process of hydrogen that injects into the natural gas pipelines, a three-dimensional T-pipe blending model is established and the flow characteristics are investigated systematically by the large eddy simulation (LES). Firstly, the mathematical formulation of hydrogen-methane blending process is provided and the LES method is introduced and validated by a benchmark gas blending model having experimental data. Subsequently, the T-pipe blending model is presented, and the effects of key parameters, such as the velocity of main pipe, hydrogen blending ratio, diameter of hydrogen injection pipeline, diameter of main pipe and operating pressure on the hydrogen-methane blending process, are studied systematically. The results show that, under certain conditions, the gas mixture will be stratified downstream of the blending point, with hydrogen at the top of the pipeline and methane at the bottom of the pipeline. In the no-stratified scenario, the mixing distance increases at lower hydrogen mixing ratio and larger diameter of the hydrogen injection pipe or the main pipe. Finally, based on the numerical results, the underlying physics of the stratification phenomenon during the blending process are explored and an indicator for stratification is proposed using the ratio between the Reynolds numbers of the natural gas and hydrogen.

BackgroundDiabetes mellitus (DM) is the common comorbidity with lung cancer (LC), and metabolic disorders have been identified as significant contributors to the pathogenesis of both DM and LC. The causality between diabetes mellitus and lung cancer is still controversial. Hence, the causal effects of DM on the risk of LC was systemically investigated, and the mediating role of blood metabolites in this relationship was further explored.MethodsThis study utilized a comprehensive Mendelian randomization (MR) analysis to investigate the association between diabetes mellitus and lung cancer. The inverse variance weighted method was employed as the principle approach. MR Egger and weighted median were complementary calculations for MR assessment. A two-step MR analysis was performed to evaluate the mediating effects of blood metabolites as potential intermediate factors. Simultaneously, sensitivity analyses were performed to confirm the lack of horizontal pleiotropy and heterogeneity.ResultsThe two-sample MR analysis illustrated the overall effect of type 1 diabetes mellitus (T1DM) on lung squamous cell carcinoma (LUSC) (OR: 1.040, 95% CI: 1.010–1.072, p = 0.009). No causal connection was found between T2DM and the subtypes of lung cancer. Two-step MR identified two candidate mediators partially mediating the total effect of T1DM on LUSC, including glutamine conjugate of C6H10O2 levels (17.22%) and 2-hydroxyoctanoate levels (5.85%).ConclusionOur findings supported a potentially causal effect of T1DM against LUSC, and shed light on the importance of metabolites as risk factors in understanding this relationship.

ABSTRACT: Cadmium (Cd) is a heavy metal that pollutes the environment and threatens human and animal health via the food chain. The spleen is one of the target organs affected by Cd toxicity. However, the mechanism of Cd toxicity is not fully understood. In this study, 80 chicks were allocated into 4 groups (n = 20) and exposed to different doses of CdCl2 (0 mg/kg, 35 mg/kg, 70 mg/kg and 140 mg/kg) for 90 d. The pathological changes in the spleen, mitochondrial dynamics-related factors, cytochrome P450 (CYP450) enzyme system contents, activities, transcription levels, nuclear receptors (NRs) response molecule levels, and mitochondrial unfolded protein-related factors were detected. The findings indicate that exposure to Cd significantly leads to spleen injury. In Cd groups, the total contents of CYP450 and cytochrome b5 (Cyt b5) increased, and the activities of the CYP450 enzyme system (APND, ERND, AH, and NCR) changed. The NRs response was induced, and the gene levels of AHR/CAR and corresponding CYP450 isoforms (CYP1B1, CYP1A5, CYP1A1, CYP2C18, CYP2D6 and CYP3A4) were found altered. The study found that Cd exposure altered the mRNA expression levels of mitochondrial dynamics-related factors, such as OPA1, Fis1, MFF, Mfn1, and Mfn2, breaking mitochondrial fusion and cleavage and ultimately leading to mitochondrial dysfunction. Changes were detected in the gene levels of several mitochondrial unfolded protein response (mtUPR)-related factors, namely (SIRT1, PGC-1α, NRF1, TFAM, SOD2, and HtrA2). Cd also altered the gene levels of mitochondrial function-related factors (VDAC1, Cyt-C, COA6, PRDX3, RAF and SIRT3). It is showed that Cd can initiate the NRs response, influence the homeostasis of the CPY450 enzyme system, trigger the mtUPR, impair mitochondrial function, and ultimately lead to Cd toxicity in the spleen of chickens.

ObjectivesEndoscopic retrograde cholangiopancreatography(ERCP) with endoscopic metallic biliary endoprosthesis(EMBE) serves as a crucial palliative treatment for advanced malignant biliary obstruction(MBO). While endoscopic nasobiliary drainage(ENBD) effectively reduces post-ERCP cholangitis (PEC) incidence, its impact on PEC in MBO patients is unclear. This study evaluates ENBD’s effects on PEC in patients undergoing EMBE and identifies risk factors.MethodsThis retrospective cohort study at the First Hospital of Jilin University involved MBO patients who underwent EMBE from September 2011 to September 2022. Propensity score matching (PSM) was applied to minimize selection bias. Primary and secondary outcomes included the incidence and recovery rate/time of PEC, biliary drainage success, and hospitalization duration. Univariate, multivariate, and Lasso regression analyses identified independent risk factors.ResultsIn this study of 1,008 patients, 730 were analyzed after PSM(365 each in the EMBE+ENBD and EMBE groups). No significant differences were observed in PEC incidence(10.7% vs 11.2%, p=0.9057) or recovery rates(48.7% vs 31.7%, p=0.1855). However, PEC recovery time was shorter in the EMBE+ENBD group(4.0 days [3.0, 6.0] vs 5.0 days [4.0, 7.5], p=0.0240), as was hospitalization duration(6.0 days [4.0, 8.0] vs 7.0 days [5.0, 10.0], p=0.0146), and a higher success rate of biliary drainage(54.0% vs 43.3%, p=0.0049). Tumor location(HR 1.10, 95% CI 1.00-1.20) and preoperative total bilirubin(HR 2.13, 95% CI 1.66-2.73) were identified as independent risk factors.ConclusionIn this large-scale PSM study, ENBD did not reduce PEC incidence but expedited recovery and shortened hospital stays. Patients with hilar MBO of Bismuth III-IV or high preoperative bilirubin were more prone to PEC.

Background: Exposed, infected and necrotic tendons often occur in the middle and late stages of diabetic foot ulcers (DFUs). The exposed tendon is both a potential source and route of infection, which prolongs the treatment period and affects recovery, leading to amputation and even death. Therefore, management of the exposed tendon in patients with DFU is the key to treatment. This study aimed to evaluate the clinical efficacy of Shengji ointment combined with bromelain in the treatment of DFU with tendon exposure and to provide clinical treatment options and evidence-based medicine. Methods: This study was a multicenter, nonblinded, randomized, positive controlled clinical trial involving 180 patients with DFU with tendon exposure at four tertiary-grade A-class hospitals. The included patients were randomly assigned 1:1 to an observation group (n = 90) that received Shengji ointment combined with bromelain and a control group (n = 90) that received hydrocolloid dressing, with dressing changes once daily for 4 weeks. Patients in both groups continued with conventional treatments, such as blood glucose and blood pressure medication, lipid regulation, and antiplatelets. The primary outcome measure was wound coverage with granulation tissue. The secondary outcome measures included the wound healing rate, time to granulation, Maryland foot score, time to debridement of necrotic tendon tissue, and granulation tissue score. We performed measurements before enrollment and after the end of treatment for comparison. Results: There was no significant difference in the baseline data between the two groups before treatment (P > 0.05). After treatment, the primary outcome indicators of the two groups were compared, and the wound granulation tissue coverage rate of the treatment group was greater than that of the control group (P = 0.003). For the secondary outcome outcomes, the wound healing rate, time to granulation, Maryland foot function score, time to debridement of necrotic tendon tissue, and granulation tissue score in the treatment group were significantly better than those in the control group (P

Objective Surgical decision‐making for congenital kyphosis (CK) with failure of anterior segmentation (type II) has been contradictory regarding the trade‐off between the pursuit of correction rate and the inherent risk of the osteotomy procedure. This study was designed to compare the clinical and radiographic measurement in type II CK underwent SRS‐Schwab Grade 4 osteotomy and vertebral column resection (VCR), the most‐adapted osteotomy techniques for CK, and to propose the strategy to select between the two procedures. Methods This retrospective observational comparative study evaluated surgical outcomes in type II CK patients underwent VCR or SRS‐Schwab Grade 4 osteotomy at our institution between January 2015 and January 2020. Patients operated with VCR and SRS‐Schwab Grade 4 osteotomy were allocated to Group 1 and Group 2 respectively. Radiographic parameters and SRS‐22 quality of life metrics were assessed at pre‐operation, post‐operation, and during follow‐up visits for both groups, allowing for a comprehensive comparison of surgical outcomes. Results Thirty‐one patients (19 patients in Group 1 and 12 patients in Group 2) aged 16.3 ± 10.4 years were recruited. Correction of segmental kyphosis was similar between groups (51.1 ± 17.6° in Group 1 and 48.4 ± 19.8° in Group 2, p = 0.694). Group 1 had significantly longer operation time (365.9 ± 81.2 vs 221.4 ± 78.9, p

Abstract Necrotizing enterocolitis (NEC) involves intestinal epithelial damage and inflammatory response and is associated with high morbidity and mortality in infants. To improve therapeutic prospects, elucidating underlying molecular mechanisms of intestinal epithelial damage during NEC is of the essence. Poly (ADP-ribose) polymerase 1 (PARP1)-dependent parthanatos is a programmed inflammatory cell death. In the present study, the presence of parthanatos-associated proteins PARP1 and poly (ADP-ribose) (PAR), along with high expression of DNA damage-associated biomarkers, 8-hydroxy-2’-deoxyguanosine (8-OHdG) and phosphorylation of histone H2AX (γH2AX), were discovered in the intestinal tissues of NEC infants. Additionally, the upregulated expression of PARP1 and PAR in NEC intestinal tissues correlated distinctly with clinical indices indicative of NEC incidence and severity. Furthermore, we demonstrated that inhibiting the expression of parthanatos-associated proteins, by either pharmacological blockage using 3-aminobenzamide (3-AB), an inhibitor of PARP1, or genetic knockout using Parp1-deficient mice, resulted in substantial improvements in both histopathological severity scores associated with intestinal injury and inflammatory reactions. Moreover, in an in vitro NEC model, reactive oxygen species (ROS)-induced DNA damage promoted the formation of PAR and nuclear translocation of apoptosis-inducing factor (AIF), thus activating PARP1-dependent parthanatos in Caco-2 cells and human intestinal organoids. Our work verifies a previously unexplored role for parthanatos in intestinal epithelial damage during NEC and suggests that inhibition of parthanatos may serve as a potential therapeutic strategy for intervention of NEC.

Abstract Exploring novel diagnostic and therapeutic biomarkers is extremely important for osteosarcoma. YME1 Like 1 ATPase (YME1L), locating in the mitochondrial inner membrane, is key in regulating mitochondrial plasticity and metabolic activity. Its expression and potential functions in osteosarcoma are studied in the present study. We show that YME1L mRNA and protein expression is significantly elevated in osteosarcoma tissues derived from different human patients. Moreover, its expression is upregulated in various primary and immortalized osteosarcoma cells. The Cancer Genome Atlas database results revealed that YME1L overexpression was correlated with poor overall survival and poor disease-specific survival in sarcoma patients. In primary and immortalized osteosarcoma cells, silencing of YME1L through lentiviral shRNA robustly inhibited cell viability, proliferation, and migration. Moreover, cell cycle arrest and apoptosis were detected in YME1L-silenced osteosarcoma cells. YME1L silencing impaired mitochondrial functions in osteosarcoma cells, causing mitochondrial depolarization, oxidative injury, lipid peroxidation and DNA damage as well as mitochondrial respiratory chain complex I activity inhibition and ATP depletion. Contrarily, forced YME1L overexpression exerted pro-cancerous activity and strengthened primary osteosarcoma cell proliferation and migration. YME1L is important for Akt-S6K activation in osteosarcoma cells. Phosphorylation of Akt and S6K was inhibited after YME1L silencing in primary osteosarcoma cells, but was strengthened with YME1L overexpression. Restoring Akt-mTOR activation by S473D constitutively active Akt1 mitigated YME1L shRNA-induced anti-osteosarcoma cell activity. Lastly, intratumoral injection of YME1L shRNA adeno-associated virus inhibited subcutaneous osteosarcoma xenograft growth in nude mice. YME1L depletion, mitochondrial dysfunction, oxidative injury, Akt-S6K inactivation, and apoptosis were detected in YME1L shRNA-treated osteosarcoma xenografts. Together, overexpressed YME1L promotes osteosarcoma cell growth, possibly by maintaining mitochondrial function and Akt-mTOR activation.

Abstract Aims Acute myocardial infarction (AMI) is a cardiovascular disease with high morbidity and mortality. We collected patients with AMI from the Medical Information Mart for Intensive Care IV (v2.0) database and explored the association between serum albumin‐corrected anion gap (ACAG) level and mortality in patients with AMI. Methods and results Data of adult patients with AMI were collected. According to the 360 day prognosis, patients were divided into survival and non‐survival groups. Based on the ACAG level, patients were then divided into normal and high ACAG groups. Cox hazard proportional models and restricted cubic splines (RCSs) were used to investigate the correlation between ACAG and mortality. Kaplan–Meier curves were created to compare the cumulative survival rates between the high and normal ACAG groups. The receiver operating characteristic (ROC) curve was used to analyse the predictive value of ACAG for the prognosis of patients with AMI. Sensitivity and subgroup analyses were conducted to revalidate the results. Finally, 1783 patients were included. Elevated ACAG (>20 mmol/L) was significantly associated with 30 and 360 day mortality (P 20 mmol/L) was an independent risk factor of increased all‐cause mortality in patients with AMI (hazard ratio 1.423, 95% confidence interval 1.206–1.678, P

Abstract Background Cardiac arrest (CA) is one of the leading causes of death globally, characterized by high incidence and mortality. It is of particular significance to determine the prognosis of patients with CA early and accurately. Therefore, we aim to investigate the correlation between albumin-corrected calcium (ACC) and the prognosis in patients diagnosed with CA. Methods We retrospectively collected data from medical information mart for intensive care IV database. Patients were divided into two groups (survival and non-survival groups), according to the 90-day prognosis. In the Restricted cubic spline (RCS) analysis, the cut-off values (8.86 and 10.32) were obtained to categorize patients into three groups: low ACC group ( 10.32). The least absolute shrinkage and selection operator with a ten-fold cross-validation regression analysis was performed to identify variables linked to the mortality. The inverse probability treatment weighting (IPTW) was used to address the confounding factors, and a weighted cohort was generated. RCS, Kaplan–Meier curve, and Cox regression analyses were used to explore the relationship between ACC and the mortality. Sensitivity analysis was employed to validate the stability of the results. Results Cut-off values for ACC of 8.86 and 10.32 were determined. RCS analyses showed that there was an overall non-linear trend relationship between ACC and the risk of 90-day and 360-day mortalities. After IPTW adjustment, compared to the moderate ACC group, the 90-day and 360-day mortalities in the high ACC group were higher (P 10.32) were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P

Abstract Autistic Children often struggle with social interaction and communication, studies have found that many of them prefer to interact with objects than people. However, there is a lack of research exploring the specific characteristics and factors involved in interactions within families with autistic children where objects are the center of the interaction. This paper describes the process and findings of a diary study exploring how young autistic children interact with their families through objects in natural scenarios. A one-week diary study was conducted with six families with young autistic children. Diary videos were recorded onsite and coded later according to a social interaction behavior scheme with corresponding diary entries. Qualitative data analysis was conducted to reveal possible patterns. Results revealed ongoing difficulties in establishing and maintaining family interaction and identified influential factors of object-centered family interaction. The most prevalent pattern observed was parents taking the lead in interactions, followed by the child's confirmation response. Remarkably, daily necessities emerged as potential physical mediums for enhancing family interactions, opening avenues for exploring tangible designs in human–computer interaction. These findings offer valuable implications for future research and the development of innovative designs that promote enriching interactions for autistic children and their families.

Abstract Background The global prevalence of VCI has increased steadily in recent years, but diagnostic biomarkers for VCI in patients with non-disabling ischemic cerebrovascular incidents (NICE) remain indefinite. The primary objective of this research was to investigate the relationship between peripheral serological markers, white matter damage, and cognitive function in individuals with NICE. Methods We collected clinical data, demographic information, and medical history from 257 patients with NICE. Using the MoCA upon admission, patients were categorized into either normal cognitive function (NCF) or VCI groups. Furthermore, they were classified as having mild white matter hyperintensity (mWMH) or severe WMH based on Fazekas scores. We then compared the levels of serological markers between the cognitive function groups and the WMH groups. Results Among 257 patients with NICE, 165 were male and 92 were female. Lymphocyte count (OR = 0.448, P

Objective Clinical and radiographic degenerative spondylolisthesis (CARDS) classification was proposed to differentiate homogenous lumbar degenerative spondylolisthesis (LDS) subgroups. The sitting radiograph exhibited lumbar malalignment with maximum lumbar kyphosis, intervertebral kyphosis, and spondylolisthesis.This study aimed to assess the sitting radiograph for distribution of clinical and radiographic degenerative spondylolisthesis classification, and to elucidate its significance for exhibiting kyphotic alignment (CARDS type D) and segmental instability. Methods A cohort of 101 patients with symptomatic lumbar degenerative spondylolisthesis (LDS) between September 2018 and December 2020 were recruited. The distribution and relibility of CARDS classification with or without sitting radiograph was assessed. The translational and angular range of motion and segmental instability was also evaluated. Univariate analysis of variance was used for multiple groups, and the least significant difference for two groups. Kappa consistency test of intrarater and interrater was evaluated for CARDS classification with or without sitting radiograph. Chi‐square test was used to compare paried categorical data. Results Utility of sitting radiographs for CARDS classification revealed higher percentage of type D than that without the sitting radiograph (p

Abstract Background The molecular targets and associated mechanisms of hepatocellular carcinoma (HCC) have been widely studied, but the roles of PDZK1 in HCC are unclear. Therefore, the aim of this study is to explore the role and associated mechanisms of PDZK1 in HCC. Results It was found that the expression of PDZK1 in HCC tissues was higher than that in paired paracancerous tissues. High expression of PDZK1 was associated with lymph node metastasis, degree of differentiation, and clinical stage. Upregulation of PDZK1 in HCC cells affected their proliferation, migration, invasion, apoptosis, and cell cycle, and also induced PI3K/AKT activation. PDZK1 is a downstream target gene of miR-101-3p. Accordingly, increase in the expression of miR-101-3p reversed the promotive effect of PDZK1 in HCC. Moreover, PDZK1 was found to accelerate cell proliferation and promote the malignant progression of HCC via the PI3K/AKT pathway. Conclusion Our study indicated that the miR-101-3p/PDZK1 axis plays a role in HCC progression and could be beneficial as a novel biomarker and new therapeutic target for HCC treatment.

Background Pulmonary hypertension (PH) is often caused by left heart disease (group 2 PH) , which is difficult to diagnose early and with a high mortality rate. Potassium channel dysfunction is a marker of PH, however, the epidemiological data of the disease and the effect of potassium ions on PH still remain unclear. Objective To investigate the correlation of serum potassium level with myocardial markers, echocardiographic indicators and length of hospital stay in patients with group 2 PH, and evaluate the predictive value of serum potassium levels for the severity of group 2 PH, so as to provide the oretical basis for clinical diagnosis and treatment. Methods The clinical data of 400 adult inpatients diagnosed with group 2 PH in the First Hospital of Shanxi Medical University from January 2020 to December 2021 were retrospectively collected as follows: (1) general data: gender, age, BMI, length of hospital stay, smoking status, smoking index (SI) and drinking history; (2) underlying diseases (diabetes mellitus, hypertension) ; (3) laboratory data: serum potassium level, myocardial markers[procalcitonin, N-terminal pro-brain natriuretic peptide (NT-proBNP) , cardiac troponin I, cardiac troponin T, creatine kinase-MB], echocardiographic indicators (left atrial diameter, right ventricular diameter, right atrial area, left ventricular ejection fraction, shortening fraction, peak tricuspid regurgitation velocity, pulmonary artery systolic pressure) . The patients were divided into 5.5 mmol/L group (n=3) according to the serum potassium level. Spearman correlation analysis was used to explore the correlation of serum potassium level with myocardial markers and echocardiographic indicators. Log-rank (Mantel-Cox) test was used to compare the discharge rate of patients with different serum potassium levels. Receiver operating characteristic curve (ROC curve) was plotted to evaluate the predictive value of serum potassium level for the severity of group 2 PH. Results Procalcitonin and NT-proBNP levels of patients in the >5.5 mmol/L group were significantly higher than the 5.5 mmol/L to investigate its relationship with length of hospital stay in depth. Log-rank (Mantel-Cox) testresults showed that for group 2 PH patients greater than average hospitalization levels, there was a significant difference in cumulative hospitalization rates among patients with different serum potassium levels (5.5 mmol/L) (P=0.022) . ROC analysis showed that the diagnostic value of serum potassium level for non-mild PH (AUC=0.577, cut-off value=3.91 mmol/L, sensitivity=64.7%, specificity=52.5%) was similar to that of NT-proBNP (AUC=0.585, cut-off value=1 070.69 pg/mL, sensitivity=78.1%, specificity=39.6%) , which can effectively predict the severity of group 2 PH. Conclusion Serum potassium level can predict the severity of group 2 PH and the length of hospital stay. Intervention of serum potassium levels may be one of the new approach to prevent and treat PH.

Objective Isthmic spondylolisthesis (IS) is distinguished by a congenital defect or acquired fracture of the pars interarticularis. Numerous studies on L5 low‐grade IS have been carried out; however, there is a paucity of data regarding the condition of L5 IS concomitant with L4/5 disc herniation. This study aimed to identify the incidence rate and to illustrate the possible risk factors for L4/5 disc herniation in L5 low‐grade IS patients. Methods A total of 268 consecutive patients diagnosed as L5/S1 low‐grade IS between May 2017 and May 2022 were retrospectively enrolled in this study. Depending on the presence of L4/5 disc herniation or not, patients were divided into an L4/5 disc herniation group (L4/5 DH) and an L4/5 non‐disc herniation group (L4/5 non‐DH). Radiographic parameters were measured, and the ratios of L4–S1 segmental lordosis (SL) to lumbar lordosis (LDI), L4 inferior endplate (IEP) to L5 superior endplate (SEP) (L4 IEP/L5 SEP), and L5 IEP to S1 SEP (L5 IEP/S1 SEP) were compared between groups. The Pfirrmann grade of the L4/5 disc and the L5/S1 disc, and Roussouly classifications of each patient were also recorded. Univariate analysis (including independent‐samples t‐test and χ2‐test) and multiple logistic regression analysis were performed to analyze the data. Results There were 40 patients (14.9%) in the L4/5 DH group. The Roussouly classification differed significantly between groups. As demonstrated by the Pfirrmann grade, the L4/5 DH group showed more advanced disc degeneration at L4/5 than the L4/5 non‐DH group. In contrast to the L4/5 non‐DH group, the L4/5 DH group had a significantly larger L4 IEP, L4 IEP/L5 SEP, S1 SEP, and LDI while smaller L4/5 disc angle, L4/5 disc height, slip percentage, lumbar lordosis, and sacral slope. Multivariate logistic regression analysis revealed that higher L4/5 disc Pfirrmann grade (p = 0.004), decreased L4/5 disc height (p

Abstract As museums continue to play an increasingly significant role in the preservation, innovation, and dissemination of cultural heritages, the products sold in their souvenir shops have become a vital carrier of cultural and creative industries. The creativity of these products has drawn intensive attention from various industries. However, the evaluation of museum products’ creativity still lacks objectivity, scientific rigour, and systematisation. This study aims to construct a contextual and comprehensive measurement model to evaluate the creativity of products purchased in souvenir shops affiliated with urban historical museums in China. Based on the literature, ten related hypotheses were introduced, and a conceptual model was illustrated. Six relevant dimensions and 28 corresponding indicators were identified, and then a 7-point Likert-styled questionnaire was developed. An online survey was conducted, which invited 931 participants to take part. Among them, 708 responses are valid (rate 76.05%). The overall reliability of the survey is 0.96 (Cronbach’s α). Then, exploratory factor analysis, confirmatory factor analysis and a structural equation modelling analysis using SPSS and SmartPLS were conducted. The results supported most hypotheses proposed by this study and confirmed the validity of the museum product creativity measurement (MPCM). The validated instrument comprises five dimensions: Affect, Usefulness, Aesthetics, Cultural Values and Novelty, with a total of 21 indicators. Additionally, the findings revealed that Aesthetics mediates Affect, and Cultural Values mediate Usefulness. Moreover, a negative moderating effect of Educational Level on the perception of Cultural Values was detected.

Auricularia heimuer is drought tolerant, but the mechanism underlying its physiological response to drought has not been systematically studied. We selected 13 strains of A. heimuer and simulated drought stress using a complete yeast medium (CYM) containing 20% polyethylene glycol (PEG), while the medium used for the control treatments did not contain PEG. Strains were cultured on a shaker incubator at 25 °C at 120 rpm for 15 days under dark conditions. The contents of soluble sugars (SS) and soluble proteins (SP), the activities of superoxide dismutase (SOD) and catalase (CAT), the content of malondialdehyde (MDA), and the biomass were measured. Between the 20% PEG treatment and the control, as well as among different strains, there were significant differences in all of the physiological indices. The tested strains were classified into the following four categories according to their membership function values: the first category consisted of the highly drought-tolerant strain A; the second consisted of the drought-tolerant strains A127 and C; the third consisted of the moderately drought-tolerant strains A124, A14, A386, A462, A184, A496, A125, and B; and the fourth consisted of the drought-sensitive strains A356 and A508. Transcriptome analysis was performed on C before and after drought stress treatment, and 1762 differentially expressed genes (DEGs) were obtained, including 798 up- and 964 down-regulated genes. Through KEGG enrichment analysis, it was found for the first time that the synthesis pathway for trehalose in A. heimuer is trehalose phosphate synthase–trehalose phosphate phosphatase (TPS-TPP), which is involved in the response of A. heimuer to drought stress. In addition, two key enzyme genes involved in trehalose synthesis, namely trehalose-6-phosphate synthase (AhTPS) and trehalose-6-phosphate phosphatase (AhTPP), were significantly up-regulated after drought stress. The trehalose content significantly increased in 11 strains after drought stress treatment. This study discovered, for the first time, that the synthesis pathway of trehalose is involved in the response of edible fungi to drought stress, thus providing a reference for the genetic improvement of A. heimuer and the selection of drought-tolerant strains, laying a theoretical foundation for the resistance breeding of other edible fungi.

The formation and evolution of SmCo5/Sm2Co17 (1:5H/2:17R/H) cellular structures play an essential role in understanding the coercivity of Sm-Co magnets. Herein, the pristine and different elemental-doped 1:5/2:17R and 1:5/2:17H interfaces are investigated to evaluate the elemental site preferences, interface configurations, and magnetic properties in Sm2Co17-type magnets with general alloy elements M (M = Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Al, Si, and Ga). Comparing the calculated results of 1:5/2:17H with those of the 1:5/2:17R interface, we found that Cu and Mn always segregate at the 1:5 phase, and Ga elements first appear at the 1:5 phase in 1:5/2:17H and then change to the 2:17 phase in 1:5/2:17R. While Ti, V, Fe, Zn, Al, and Si elements always tend to segregate at the 2:17 phase, Ni first segregates at the 2:17 phase in 1:5/2:17H and then occupies the 1:5 phase of 1:5/2:17R. The 1:5/2:17H interface along the c-axis expands about 1.98~3.28%, while the 1:5/2:17R interface slightly shrinks about 0.04~0.87% after element doping. This suggests that different interface stress behaviors exist for high-temperature and room-temperature phase Sm2Co17-type magnets. Furthermore, Mn, Fe, and Ga doping improved the saturation magnetization strength. Our results provide new insights into understanding the effect of elemental doping at the interfaces of 1:5H/2:17R cellular structures.