High-resolution full-coverage ozone (O3) estimates using a data-driven spatial random forest model in Beijing-Tianjin-Hebei region, China.

The Beijing-Tianjin-Hebei (BTH) region is severely polluted by ozone (O3). Accurate O3 estimates are essential for identifying high-polluted zones and developing targeted interventions to relieve the burden of diseases. Although many studies have estimated high-resolution O3 concentrations in BTH, the estimation accuracies are still insufficient. In this study, we incorporated data-driven spatial weight matrices (DDWs) into a random forest (RF) model to fully utilize both the spatial homogeneity and heterogeneity of maximum daily 8-h ozone concentration (MDA8O3), and obtained full-coverage MDA8O3 concentrations at 1 km×1 km in BTH from 2014 to 2022. DDW-RF exhibited satisfactory accuracy (10-fold cross-validation R2 =0.937, RMSE=13.919 µg/m3). Overall O3 level presented a spatial pattern of lower in the north and higher in the southeast and showed a distinct temporal trend, i.e., first increasing and then decreasing during 2014-2021 and increasing slightly in 2022. The accurate MDA8O3 estimates indicates that more attention and resources should be poured into the areas adjacent to Bohai Rim, Shandong and Henan. Regulated operation of factories under specific meteorological conditions and upgrading industrial structure and production modes are recommended to mitigate the formation of O3 precursors and reduce O3 generation. Our findings provide evidence and reference for environmental cleaning policies and targeted interventions.

High-resolution modeling and projection of heat-related mortality in Germany under climate change.

BACKGROUND: Heat has become a leading cause of preventable deaths during summer. Understanding the link between high temperatures and excess mortality is crucial for designing effective prevention and adaptation plans. Yet, data analyses are challenging due to often fragmented data archives over different agglomeration levels. METHOD: Using Germany as a case study, we develop a multi-scale machine learning model to estimate heat-related mortality with variable temporal and spatial resolution. This approach allows us to estimate heat-related mortality at different scales, such as regional heat risk during a specific heatwave, annual and nationwide heat risk, or future heat risk under climate change scenarios. RESULTS: We estimate a total of 48,000 heat-related deaths in Germany during the last decade (2014-2023), and the majority of heat-related deaths occur during specific heatwave events. Aggregating our results over larger regions, we reach good agreement with previously published reports from Robert Koch Institute (RKI). In 2023, the heatwave of July 7-14 contributes approximately 1100 cases (28%) to a total of approximately 3900 heat-related deaths for the whole year. Combining our model with shared socio-economic pathways (SSPs) of future climate change provides evidence that heat-related mortality in Germany could further increase by a factor of 2.5 (SSP245) to 9 (SSP370) without adaptation to extreme heat under static sociodemographic developments assumptions. CONCLUSIONS: Our approach is a valuable tool for climate-driven public health strategies, aiding in the identification of local risks during heatwaves and long-term resilience planning.

Heat is becoming a major cause of preventable deaths during the summer. We developed a computer model to estimate heat-related deaths at specific times and in different districts. Using this model for Germany, we estimate that over the past decade (2014­2023), around 48,000 deaths were heat-related, with most occurring during heatwaves. For example, a heatwave from July 7­14, 2023, contributed to 1100 out of 3900 heat-related deaths that year. Our model also suggests that, without adaptation, heat-related deaths in Germany could increase remarkably due to climate change. The insights from our model can help identify areas at high risk and support long-term public health planning to reduce the impact of heatwaves.

Application of third-generation sequencing technology for identifying rare α- and ß-globin gene variants in a Southeast Chinese region.

BACKGROUND: Third-generation sequencing (TGS) based on long-read technology has been gradually used in identifying thalassemia and hemoglobin (Hb) variants. The aim of the present study was to explore genotype varieties of thalassemia and Hb variants in Quanzhou region of Southeast China by TGS. METHODS: Included in this study were 6,174 subjects with thalassemia traits from Quanzhou region of Southeast China. All of them underwent common thalassemia gene testing using the DNA reverse dot-blot hybridization technology. Subjects who were suspected as rare thalassemia carriers were further subjected to TGS to identify rare or novel α- and ß-globin gene variants, and the results were verified by Sanger sequencing and/or gap PCR. RESULTS: Of the 6,174 included subjects, 2,390 (38.71%) were identified as α- and ß-globin gene mutation carriers, including 40 carrying rare or novel α- and ß-thalassemia mutations. The αCD30(-GAG)α and Hb Lepore-Boston-Washington were first reported in Fujian province Southeast China. Moreover, the ßCD15(TGG> TAG), ßIVS-II-761, ß0-Filipino(~ 45 kb deletion), and Hb Lepore-Quanzhou were first identified in the Chinese population. In addition, 35 cases of Hb variants were detected, the rare Hb variants of Hb Jilin and Hb Beijing were first reported in Fujian province of China. Among them, one case with compound αααanti3.7 and Hb G-Honolulu variants was identified in this study. CONCLUSION: Our findings may provide valuable data for enriching the spectrum of thalassemia and highlight the clinical application value of TGS-based α- and ß-globin genetic testing.

TRIM40 interacts with ROCK1 directly and inhibits colorectal cancer cell proliferation through the c-Myc/p21 axis.

BACKGROUND: Colorectal cancer (CRC) is the most common malignancy of the digestive tract, and to date, morbidity and mortality rates remain high. While existing therapeutic methods have achieved certain effective outcomes, there are still many problems in treating this disease. Therefore, it is still urgent to constantly find new therapeutic targets in CRC that could lead to new therapeutics. METHODS: Immunohistochemistry, Real-time PCR and Western Blot were employed to measure mRNA and protein levels of the target protein, respectively. The proliferation ability of CRC cells was evaluated using ATP assay, Soft agar assay, and nude mouse subcutaneous tumorigenesis assay. Protein Degradation Assay was conducted to determine protein degradation rate, while Ubiquitination assay was used to assess the ubiquitination modification level of target proteins. Immunoprecipitation assay was used to study protein interactions, and pull-down assay was employed to investigate direct interactions between proteins. RESULTS: TRIM40 was significantly down-regulated in CRC tissues, with its expression levels positively correlating with disease prognosis. Using both in vitro and in vivo approaches, it was demonstrated that TRIM40 could significantly inhibit the proliferation of CRC cells. Molecular mechanism studies showed that TRIM40 directly binds to and ubiquitinates ROCK1 protein, accelerating its degradation and subsequently reducing the stability of c-Myc protein. This cascade of events results in the release of transcriptional inhibition of p21 by c-Myc, leading to increased p21 expression and G0/G1 phase arrest in CRC cells. CONCLUSION: This research suggests that TRIM40 could be a valuable therapeutic target for the treatment of CRC.

Predictive value of IL-8 for mortality risk in elderly sepsis patients of emergency department.

BACKGROUND: Sepsis significantly impacts morbidity and mortality, particularly among older adults. Despite extensive research, early recognition and prognosis prediction of sepsis remain challenging. IL-8, a chemokine produced by inflammatory cells like monocytes and endothelial cells, has shown potential in predicting mortality in sepsis patients, though its role in elderly sepsis remains unexplored. OBJECTIVES: The present study aimed to explore the predictive ability of interleukin-8 (IL-8) for mortality risk in elderly septic patients. METHODS: 220 elderly sepsis patients were included in the present study. Serum samples were obtained within 1 h of admission to assess serum IL-8, white blood cell (WBC), procalcitonin (PCT), C-reactive protein (CRP), and lactic acid (LAC) levels. The Sequential Organ Failure Score (SOFA) and Acute Physiological and Chronic Health Assessment II (APACHE II) were recorded. Logistic regression analysis was employed to identify independent predictors of mortality within 28 days for elderly patients diagnosed with sepsis. Further, the capacity of these factors to predict 28-day mortality within this patient cohort was evaluated. RESULTS: SOFA score, APACHE II score, LAC, and IL-8 were all significant independent predictors for 28-day mortality in elderly sepsis patients (P < 0.05). The AUC of the ROC curve for IL-8 was calculated to be 0.701, indicating a moderately predictive performance. In comparison, the AUC for LAC was marginally higher at 0.708. Nevertheless, the results of the statistical analysis revealed no significant difference in the predictive value between IL-8 and LAC. Moreover, the present findings indicate that the combined assessment of IL-8 and SOFA score demonstrated superior predictive value for mortality compared to using IL-8 alone. CONCLUSIONS: IL-8 LAC, APACHE II, and SOFA can be considered independent predictors factors for mortality of elderly sepsis patients. Utilizing the combination of IL-8 and SOFA demonstrates a heightened predictive capability compared to using any single index alone.

Impact of awareness of sports policies, school, family, and community environmental on physical activity and fitness among children and adolescents: a structural equation modeling study.

BACKGROUND: Understanding the impact of environmental factors on physical activity (PA) and physical fitness (PF) is crucial for promoting a healthy lifestyle among children and adolescents. This study examines how awareness of sports policies, school, family, and community environments influence PA and PF in Chinese youth. METHODS: A cross-sectional study was conducted with 2747 children and adolescents (mean age 12.90 ± 2.49; 48.2% male) from 17 schools across five Chinese cities. Environmental factors were assessed via questionnaires, and PA levels were measured using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). PF metrics, including BMI, waist-to-height ratio, grip strength, vertical jump, and 20-m shuttle run test (20-mSRT), were measured onsite. Structural Equation Modeling (SEM) was used to explore relationships between environmental factors and PA/PF outcomes. RESULTS: The school environment scored highest (78.0 ± 9.5), while the community environment scored lowest (38.7 ± 18.0). Family environment positively influenced low-intensity PA (LPA) (ß = 0.102, P < 0.001) but negatively affected moderate-to-vigorous PA (MVPA) (ß = -0.055, P = 0.035). Community environment and awareness of sports policies positively impacted MVPA (ß = 0.216, P < 0.001; ß = 0.072, P = 0.009, respectively). Family environment positively influenced BMI reduction (ß = -0.103, P < 0.001) but negatively affected grip strength (ß = -0.063, P = 0.018). Community environment improved grip strength and 20-mSRT performance (ß = 0.088, P = 0.002; ß = 0.065, P = 0.027). CONCLUSIONS: School environments, despite high scores, do not significantly impact PA and PF. Community environments, though scoring lower, positively affect MVPA, grip strength, and 20-mSRT. Awareness of sports policies boosts MVPA, while family environments support LPA and BMI but are inversely related to MVPA and grip strength. Integrated strategies involving community infrastructure, family support, and policy awareness are essential for promoting active lifestyles among children and adolescents.

Optimal exercise dose and type for improving schizophrenia symptoms in adults: A systematic review and Bayesian network meta-analysis.

BACKGROUND: Exercise has shown promise in aiding patients with schizophrenia, potentially improving symptoms, quality of life, mood, and cognition. This review evaluates the effectiveness of different physical activities in this context, aiming to guide treatment and research towards the most beneficial exercise interventions for schizophrenia management. METHODS: This systematic review and network meta-analysis searched PubMed, MEDLINE, Embase, PsycINFO, Cochrane CENTRAL, Web of Science, and CNKI up to March 30, 2024. We utilized the "gemtc," "MBNMAdose," "metafor," and "ggplot2" packages for data analysis in R. Additionally, our results were reported as standardized mean differences with 95 % confidence intervals. To assess the risk of bias in the included studies, we used ROB2 and CINeMA tools. RESULTS: In the results section of our systematic review and network meta-analysis, we analyzed data from 47 studies involving 4031 participants. Our findings indicate that among the various exercise interventions examined for schizophrenia patients, yoga emerged as the most effective in improving Total symptoms, positive and negative symptoms. RT+AE (Resistance Training + Aerobic Exercise) showed the greatest improvement in general symptoms, whereas Tai Chi (TC) was the least effective. In terms of improvement of cognitive functions and depression, AE proved the most beneficial, while TC was found to be the least effective. EX+PT (Physical Exercise + Psychological Nursing) was identified as the most effective approach for improved quality of life, with TC again showing the least efficacy. The optimal total exercise dose to improve the patient's total symptoms was estimated to be 1200 METs-min/week. (SMD: -0.956, 95 %Crl: -1.376 to -0.536). CONCLUSIONS: Yoga, RT+AE, EX+PT, and Baduanjin have demonstrated enhanced efficacy in alleviating clinical symptoms, quality of life, depressive states, and cognitive functions in patients with schizophrenia. We identified optimal overall exercise doses and provided exercise guidance recommendations for healthcare professionals.

Correlation Analyses Between Serum Interleukin-7, Interleukin-15 and Lactate Provide Insights Into Their Potential Roles in the Regulation of Inflammation in Elderly Septic Patients.

Background: Our previous research have identified Interleukin (IL)-7 and IL-15 as prognostic biomarkers for elderly septic patients, however, little is known about the link between the serum levels of IL-7, IL-15, and lactate as well as their potential roles in the regulation of inflammation in elderly septic patients. Objectives: This study aimed at investigating the link between the serum levels of IL-7, IL-15, and lactate as well as with other factors in elderly septic patients. Design: This is a retrospective study including 129 elderly patients with sepsis who were divided into the survival group (N = 34) and the nonsurvival group (N = 95) and further subgrouped based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Methods: The baseline data and clinical parameters were recorded within 24 h upon admission. Serum levels of the cytokines were quantified by the Luminex assay. Spearman correlation analysis were performed. Results: Serum levels of IL-6, IL-7, IL-15, and tumor necrosis factor-α (TNF-α) were significantly higher in the nonsurvival group (P < .05). Correlations between serum levels of IL-7 and platelet-derived growth factor-AA (PDGF-AA), as well as correlations between IL-15, IL-6, and TNF-α were confirmed (P < .05). Both the serum levels of lactate and IL-15 correlated with the total counts of platelet (PLT) in the survival subgroup with low APACHE Ⅱ scores while the serum levels of IL-7, IL-15, and total counts of monocytes correlated with each other in the nonsurvival subgroup with different APACHE Ⅱ scores (P < .05). Conclusion: Knowledge of the regulation networks between serum levels of IL-7, IL-15, lactate, and other cytokines may provide insights into potential mechanisms in the modulation of inflammation in elderly septic patients and facilitate more prompt and accurate treatment to reduce the mortality rate.

Mendelian randomization demonstrates a causal link between peripheral circulating acylcarnitines and intracranial aneurysms.

Intracranial aneurysm (IA) is the most prevalent type of cerebral vascular disease causing life-threatening subarachnoid hemorrhages (SAH). A long-term vascular structure remodeling is considered as the main pathophysiological feature of IAs. However, the causal factors triggering the pathophysiological process are not clear. Recently, the abnormalities of peripheral circulating proteins and metabolites have been found in IAs patients and associated with the ruptures. We comprehensively investigated the potential causal relationship between blood metabolites and proteins and IAs using the mendelian randomization (MR) analysis. We applied two-sample MR to explore the potential causal association between peripheral circulating metabolites (191 blood metabolites) and proteins (1398 proteins) and IAs using data from the FinnGen study and the GWAS datasets published by Bakker et al. We identified palmitoylcarnitine, stearoylcarnitine and 2-tetradecenoylcarnitine as causal contributors of IAs and ruptures. Further two-step mediation MR analysis suggested that hypertension as one of the contributors of IAs and ruptures mediated the causal relationship between palmitoylcarnitine, stearoylcarnitine and 2-tetradecenoylcarnitine and IAs. Together, our study demonstrates that blood metabolic palmitoylcarnitine, stearoylcarnitine and 2-tetradecenoylcarnitine are causally linked to the formation and rupture of IAs. Hypertension partially mediates the causal effects.

Association between depressive duration and cognitive decline in middle-aged and older adults: Evidence from the Health and Retirement Study 2010-2018.

BACKGROUND: Depression has been found to be associated with cognitive decline, but whether longer depressive durations lead to more severe cognitive declines has not been investigated. We aimed to estimate the association between depressive duration and cognitive decline in middle-aged and older Americans based on a large-scale representative population study. METHODS: We included 27,886 participants from the Health and Retirement Study (HRS) in 2010-2018. Four datasets with 2-, 4-, 6-, and 8-year consecutive interviews were further derived which involving persistent depressed and persistent depression-free individuals. Multiple linear regressions were constructed to estimate the effects of each depressive duration on the decline in global cognition, memory and mental status. Meta-regressions were performed to test the linear trends and to explore the heterogeneity between sex, age and baseline cognitive function along with subgroup analyses. RESULTS: Depressive durations of 2, 4, 6, and 8 years were associated with reductions in global cognitive scores of 0.62 points (95% CI: 0.51-0.73), 0.77 points (95% CI: 0.60-0.94), 0.83 points (95% CI: 0.55-1.10), and 1.09 points (95% CI: 0.63-1.55), respectively, indicating a linear trend (P = 0.016). More pronounced associations were observed in middle-aged adults and females. Similar patterns were found in the associations between depressive duration and two subdomains, i.e., memory and mental health. LIMITATIONS: This study is essentially a cross-sectional study and therefore cannot provide causal associations. CONCLUSIONS: Longer depressive durations were linearly related to more severe cognitive declines. Timely intervention for depression targeted middle-aged adults can more effectively alleviate cognition-related burdens.

IL-17B alleviates the pathogenesis of systemic lupus erythematosus by inhibiting FASN-mediated differentiation of B cells.

The interleukin 17 (IL-17) family of cytokines has emerged as a critical player in autoimmune disease, including systemic lupus erythematosus (SLE). However, the role of IL-17B, a poorly understood cytokine, in the pathogenesis of SLE is still not known. In this study, we investigated the role of IL-17B in the activation and differentiation of B cells, and the pathogenesis of SLE. Intriguingly, IL-17B deficiency aggravated disease in lupus-prone mice and promoted the activation of B cells and the differentiation of germinal center B cells and plasma cells, while recombinant mouse IL-17B (rmIL-17B) significantly alleviated disease in lupus-prone mice. Mechanistically, rmIL-17B inhibited the activation of the Toll-like receptor and interferon pathways in B cells by downregulating fatty acid synthase-mediated (FASN-mediated) lipid metabolism. Loss of FASN significantly alleviated the disease in lupus-prone mice and inhibited the activation and differentiation of B cells. In addition, B cells had greater FASN expression and lower IL-17RB levels in patients with SLE than in healthy controls. Our study describes the role of IL-17B in regulating B cell activation and differentiation, and alleviating the onset of SLE. These findings will lay a theoretical foundation for further understanding of the pathogenesis of SLE.

SelK promotes glioblastoma cell proliferation by inhibiting ß-TrCP1 mediated ubiquitin-dependent degradation of CDK4.

BACKGROUND: Glioblastoma (GB) is recognized as one of the most aggressive brain tumors, with a median survival of 14.6 months. However, there are still some patients whose survival time was greater than 3 years, and the biological reasons behind this clinical phenomenon arouse our research interests. By conducting proteomic analysis on tumor tissues obtained from GB patients who survived over 3 years compared to those who survived less than 1 year, we identified a significant upregulation of SelK in patients with shorter survival times. Therefore, we hypothesized that SelK may be an important indicator related to the occurrence and progression of GBM. METHODS: Proteomics and immunohistochemistry from GB patients were analyzed to investigate the correlation between SelK and clinical prognosis. Cellular phenotypes were evaluated by cell cycle analysis, cell viability assays, and xenograft models. Immunoblots and co-immunoprecipitation were conducted to verify SelK-mediated ubiquitin-dependent degradation of CDK4. RESULTS: SelK was found to be significantly upregulated in GB samples from short-term survivors (≤ 1 year) compared to those from long-term survivors (≥ 3 years), and its expression levels were negatively correlated with clinical prognosis. Knocking down of SelK expression reduced GB cell viability, induced G0/G1 phase arrest, and impaired the growth of transplanted glioma cells in nude mice. Down-regulation of SelK-induced ER stress leads to a reduction in the expression of SKP2 and an up-regulation of ß-TrCP1 expression. Up-regulation of ß-TrCP1, thereby accelerating the ubiquitin-dependent degradation of CDK4 and ultimately inhibiting the malignant proliferation of the GB cells. CONCLUSION: This study discovered a significant increase in SelK expression in GB patients with poor prognosis, revealing a negative correlation between SelK expression and patient outcomes. Further mechanistic investigations revealed that SelK enhances the proliferation of GB cells by targeting the endoplasmic reticulum stress/SKP2/ß-TrCP1/CDK4 axis.

Collagen-rich liver-derived extracellular matrix hydrogels augment survival and function of primary rat liver sinusoidal endothelial cells and hepatocytes.

Liver sinusoidal endothelial cells (LSECs) are key targets for addressing metabolic dysfunction-associated steatotic liver disease (MASLD). However, isolating and culturing primary LSECs is challenging due to rapid dedifferentiation, resulting in loss of function. The extracellular matrix (ECM) likely plays a crucial role in maintaining the fate and function of LSECs. In this study, we explored the influence of liver-ECM (L-ECM) on liver cells and developed culture conditions that maintain the differentiated function of liver cells in vitro for prolonged periods. Porcine liver-derived L-ECM, containing 34.9 % protein, 0.045 % glycosaminoglycans, and negligible residual DNA (41.2 ng/mg), was utilized to culture primary rat liver cells in generated hydrogels. Proteomic analyses and molecular weight distribution of proteins of solubilized L-ECM revealed the typical diverse ECM core matrisome, with abundant collagens. L-ECM hydrogels showed suitable stiffness and stress relaxation properties. Furthermore, we demonstrated that collagen-rich L-ECM hydrogels enhanced LSECs' and hepatocytes' viability, and reduced the dedifferentiation rate of LSECs. In addition, hepatocyte function was maintained longer by culture on L-ECM hydrogels compared to traditional culturing. These beneficial effects are likely attributed to the bioactive macromolecules including collagens, and mechanical and microarchitectural properties of the L-ECM hydrogels.

Relationship between cognitive function and sleep quality in middle-aged and older adults for minimizing disparities and achieving equity in health: Evidence from multiple nationwide cohorts.

BACKGROUND: Cognitive decline, a heavy burden on middle-aged and older adults as global aging is aggravated, was found to be associated with sleep quality. However, the country-between heterogeneity of the association prevented us from quantifying underlying relationship and identifying potential effect modifiers for vulnerable populations and targeted interventions. METHODS: We collected data from 79,922 eligible adults in five nationwide cohorts, examined the respective relationships between cognitive function and sleep quality, synthesized underlying average relationships by meta-analysis, and explored effect modifiers by meta-regressions. Additionally, we conducted subgroup and interaction analyses to identify vulnerable populations and to determine their disparities in vulnerability. RESULTS: Although country-between disparities exist, cognitive function is robustly associated with sleep quality in middle-aged and older adults worldwide, with an effect (ß) of 0.015 [0.003, 0.027]. Executive function is the subdomain most relevant to sleep quality. Disparities in the effects of sleep quality on subdomains exist in populations with different sexes (orientation: ßfemale/ßmale = 1.615, P = 0.020), marital statuses (orientation: ßunmarried/ßmarried = 2.074, P < 0.001), education levels (orientation:ßuneducated/ßeducated = 2.074, P < 0.001) and chronic disease statuses (memory: ßunhealthy/ßhealthy = 1.560, P = 0.005). CONCLUSIONS: Cognitive function decreases with worsening sleep quality in middle-aged and older adults. Vulnerability to poor sleep generally persists in singles, females, the uneducated and people with chronic diseases. To minimize disparities and achieve health equity, we advocate for targeted interventions, i.e., encouraging socialization in singles, confirming effectiveness of hormone replacement therapy in females, employing compulsory education in middle-aged and older adults.

Factors influencing the survival status of the hip joint in post-collapse femoral head necrosis.

BACKGROUND: Despite hip function typically deteriorating in the post-collapse stage of osteonecrosis of the femoral head (ONFH), some patients can still demonstrate long-term favorable hip function, a state termed "survival with collapse". This study aims to identify the characteristics of patients suitable for "survival with collapse" in cases of ONFH. METHODS: This cross-sectional study included 65 patients (87 hips) diagnosed with post-collapse ONFH for ≥ 3 years (average 9.1 years, range 3-23 years). Hip function was assessed using the Harris Hip Score (HHS). Demographic, clinical, and radiographic data were compared between the favorable group (HHS > 80) and the poor group (HHS ≤ 80). Independent protective factors for hip function were identified by multivariate analysis and receiver operating characteristic (ROC) curve analysis was further applied to evaluate these factors' diagnostic efficacy. RESULTS: The favorable and poor groups included 46 and 41 hips, respectively. Significant differences were found in body mass index (BMI), Association Research Circulation Osseous (ARCO) stage, collapse degree, Japanese Investigation Committee (JIC) classification, necrotic size, and hip subluxation between the two groups (p < 0.05). Multivariate logistic regression identified collapse < 3 mm(OR:14.49, 95%CI: 3.52-59.68, p < 0.001), JIC types B (OR: 11.08, 95% CI: 1.07-115.12, p < 0.05) and C1(OR: 5.18, 95% CI: 1.47-18.20, p < 0.05) as independent protective factors for hip function, while BMI (OR: 0.76, 95% CI: 0.59-0.97, p = 0.029) was an independent risk factor. ROC curve analysis demonstrated that both collapse degree (AUC = 0.798, sensitivity = 91.3%, specificity = 68.3%, p < 0.0001) and JIC classification (AUC = 0.787, sensitivity = 80.4%, specificity = 73.2%, p < 0.0001) had satisfactory diagnostic value for hip function. Combining JIC classification and collapse degree (AUC = 0.868, sensitivity = 76.1%, specificity = 85.4%, p < 0.0001) significantly enhanced diagnostic efficacy compared to using either alone (p < 0.05). CONCLUSION: In ONFH, femoral head collapse does not necessarily determine a poor prognosis. Patients with mild collapse (< 3 mm) and preserved anterolateral wall are more likely to retain satisfactory hip function, making them candidates for "survival with collapse."

Single-cell transcriptomic analysis of immune cell dynamics in the healthy human endometrium.

The microenvironment of the endometrial immune system is crucial to the success of placental implantation and healthy pregnancy. However, the functionalities of immune cells across various stages of the reproductive cycle have yet to be fully comprehended. To address this, we conducted advanced bioinformatic analysis on 230,049 high-quality single-cell transcriptomes from healthy endometrial samples obtained during the proliferative, secretory, early pregnancy, and late pregnancy stages. Our investigation has unveiled that proliferative natural killer (NK) cells, a potential source of endometrial NK cells, exhibit the most robust proliferative and differentiation potential during non-pregnant stages. We have also identified similar differentiation trajectories of NK cells originating from proliferative NK cells across four stages. Notably, during early pregnancy, NK cells demonstrate the highest oxidative phosphorylation metabolism activity, and, in conjunction with macrophages and T cells, exhibit the strongest type II interferon response. With spatial transcriptome data, we have discerned that the most robust immune-non-immune interactions are associated with the promotion and inhibition of cell proliferation, differentiation and migration during four stages. Furthermore, we have compiled lists of stage-specific risk genes implicated in reproductive diseases, which hold promise as potential disease biomarkers. Our study provides insights into the dynamics of the endometrial immune microenvironment during different reproductive cycle stages, thus serving as a reference for detecting pathological changes during pregnancy.

Experimental study on axial tensile properties of basalt fibre reinforced recycled aggregate concrete.

In order to investigate the tensile properties of basalt fibre reinforced recycled aggregate concrete (BFRAC), the axial tensile tests were carried out on BFRAC specimens using the concrete axial tensile testing device. The effects of basalt fibre (BF) content and recycled aggregate replacement rate on the tensile properties of BFRAC were quantitatively investigated, and the tensile damage mechanism of BFRAC was analysed. The following conclusions were drawn: The volume fraction of BF had the most prominent effect on the axial tensile properties of BFRAC. The axial tensile strength and peak tensile strain of BFRAC both showed the change rule of first increasing and then decreasing with the increase of BF volume fraction. The replacement rate of recycled aggregate is negatively correlated with the tensile properties of BFRAC. The larger the replacement rate, the worse the tensile properties of BFRAC. When the replacement rate of recycled aggregate is 30 % and the volume fraction of BF is 0.3 %, the tensile properties of BFRAC are better, as well as its economic and environmental performance. The axial tensile strength and peak tensile strain were 2.08 MPa and 114 × 10-6, respectively. BFRAC exhibits the toughening and crack arresting effect of BF, and the crack development is relatively slow, showing more obvious plastic damage characteristics.

ß-glucan: a potent adjuvant in immunotherapy for digestive tract tumors.

The immunotherapy for gastrointestinal tumors, as a significant research direction in the field of oncology treatment in recent years, has garnered extensive attention due to its potential therapeutic efficacy and promising clinical application prospects. Recent advances in immunotherapy notwithstanding, challenges persist, such as side effects, the complexity of the tumor immune microenvironment, variable patient responses, and drug resistance. Consequently, there is a pressing need to explore novel adjunctive therapeutic modalities. ß-glucan, an immunomodulatory agent, has exhibited promising anti-tumor efficacy in preclinical studies involving colorectal cancer, pancreatic cancer, and gastric cancer, while also mitigating the adverse reactions associated with chemotherapy and enhancing patients' quality of life. However, further clinical and fundamental research is warranted to comprehensively evaluate its therapeutic potential and underlying biological mechanisms. In the future, ß-glucan holds promise as an adjunctive treatment for gastrointestinal tumors, potentially bringing significant benefits to patients.

Optimal dosage ranges of various exercise types for enhancing timed up and go performance in Parkinson's disease patients: a systematic review and Bayesian network meta-analysis.

Objective: To examine the dose-response relationship between specific types of exercise for alleviating Timed up and Go (TUG) in Parkinson's disease PD. Design: Systematic review and Bayesian network meta-analysis. Data sources: PubMed, Medline, Embase, PsycINFO, Cochrane Library, and Web of Science were searched from inception until February 5th, 2024. Study analysis: Data analysis was conducted using R software with the MBNMA package. Effect sizes of outcome indicators were expressed as mean deviation (MD) and 95% confidence intervals (95% CrI). The risk of bias in the network was evaluated independently by two reviewers using ROB2. Results: A total of 73 studies involving 3,354 PD patients. The text discusses dose-response relationships in improving TUG performance among PD patients across various exercise types. Notably, Aquatic (AQE), Mix Exercise (Mul_C), Sensory Exercise (SE), and Resistance Training (RT) demonstrate effective dose ranges, with AQE optimal at 1500 METs-min/week (MD: -8.359, 95% CI: -1.398 to -2.648), Mul_C at 1000 METs-min/week (MD: -4.551, 95% CI: -8.083 to -0.946), SE at 1200 METs-min/week (MD: -5.145, 95% CI: -9.643 to -0.472), and RT at 610 METs-min/week (MD: -2.187, 95% CI: -3.161 to -1.278), respectively. However, no effective doses are found for Aerobic Exercise (AE), Balance Gait Training (BGT), Dance, and Treadmill Training (TT). Mind-body exercise (MBE) shows promise with an effective range of 130 to 750 METs-min/week and an optimal dose of 750 METs-min/week (MD: -2.822, 95% CI: -4.604 to -0.996). According to the GRADE system, the included studies' overall quality of the evidence was identified moderate level. Conclusion: This study identifies specific exercise modalities and dosages that significantly enhance TUG performance in PD patients. AQE emerges as the most effective modality, with an optimal dosage of 1,500 METs-min/week. MBE shows significant benefits at lower dosages, catering to patients with varying exercise capacities. RT exhibits a nuanced "U-shaped" dose-response relationship, suggesting an optimal range balancing efficacy and the risk of overtraining. These findings advocate for tailored exercise programs in PD management, emphasizing personalized prescriptions to maximize outcomes.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024506968).