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Abstract Background The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. Methods we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. Findings We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. Interpretation The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.

Summary: Increasing evidence indicates that immunotherapy is hindered by a hostile tumor microenvironment (TME) featured with deprivation of critical nutrients and pooling of immunosuppressive metabolites. Tumor cells and immunosuppressive cells outcompete immune effector cells for essential nutrients. Meanwhile, a wide range of tumor cell-derived toxic metabolites exerts negative impacts on anti-tumor immune response, diminishing the efficacy of immunotherapy. Nanomedicine with excellent targetability offers a novel approach to improving cancer immunotherapy via metabolically reprogramming the immunosuppressive TME. Herein, we review recent strategies of enhancing immunotherapeutic effects through rewiring tumor metabolism via nanomedicine. Attention is drawn on immunometabolic tactics for immune cells and stromal cells in the TME via nanomedicine. Additionally, we discuss future directions of developing metabolism-regulating nanomedicine for precise and efficacious cancer immunotherapy.

BackgroundThis study aimed to examine the associations of the Composite Dietary Antioxidant Index (CDAI) with sarcopenic obesity (SO) using the National Health and Nutrition Examination Survey (NHANES) database.MethodsData were gathered from NHANES between 2001 and 2004. To examine the relationship between CDAI and the occurrence of SO, multiple logistic regression analyses were performed. Subgroup analyses were performed to demonstrate the stability of the results. Restricted cubic splines were utilized to examine the non-linear correlations.ResultsA total of 2,333 elderly individuals were included in the study. In the multivariate logistic regression crude model, we revealed an odds ratio (OR) of 0.928 [95% confidence interval (CI), 0.891–0.965, p

Phthalates (PAEs) are synthetic compounds extensively employed in consumer products. Blood pressure (BP) in children can vary, the degree of visit-to-visit BP variability (VVV) is at least partially independent of BP. The interactions between PAEs exposure, pubertal-related genetic susceptibility and lifestyles on childhood VVV are not investigated. This study utilized data from a cohort collected from Oct 2017–2020 in Xiamen, China. Seven urine PAE metabolites were measured. The long-term VVV was characterized employing the standard deviation (SD) and average real variability. We constructed a genetic risk score (GRS) of pubertal-related genes and healthy lifestyle scores. Exposed to high levels of mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (OR=1.43, 95 %CI=1.07, 1.92) and mono-2-ethyl-5-oxohexyl phthalate (OR=1.36, 95 % CI=1.01, 1.83) was related to increased SBP-SD, and the OR for high SBP-SD related to high GRS was 1.38 (95 % CI=1.02, 1.85). Compared to participants who had low GRS and low MEHHP exposure, participants exhibiting high GRS and MEHHP levels were more likely to experience high SBP-SD (OR=2.00, P

Triclosan (TCS) is an environmental pollutant. In recent years, there has been increasing level of concern regarding the potential toxicity of TCS in animals and humans, especially its effects on the nervous system. However, whether TCS induces ADHD-like behaviour and the mechanism by which it affects neural function are unclear. The impact of 60 days of continuous exposure to TCS on the behaviour of offspring rats was assessed in this research. According to the results of this study, TCS exposure led to ADHD-like behaviour in offspring rats and activated microglia in the prefrontal cortex (PFC), inducing inflammatory factor release. In vitro studies showed that TCS increased the levels of inflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, in HMC3 cells. More importantly, we found that TCS regulated the STAT3 pathway by upregulating PKM2 via hnRNPA1. In summary, this study suggested that TCS can induce ADHD-like behaviour in offspring rats and continuously activate HMC3 microglia through the hnRNPA1-PKM2-STAT3 feedback loop, promoting inflammatory cytokine secretion.

In recent years, exposure to triclosan (TCS) has been linked to an increase in psychiatric disorders. Nonetheless, the precise mechanisms of this occurrence remain elusive. Therefore, this study developed a long-life TCS-exposed rat model, an SH-SY5Y cell model, and an atomoxetine hydrochloride (ATX) treatment model to explore and validate the neurobehavioral mechanisms of TCS from multiple perspectives. In the long-life TCS-exposed model, pregnant rats received either 0 mg/kg (control) or 50 mg/kg TCS by oral gavage throughout pregnancy, lactation, and weaning of their offspring (up to 8 weeks old). In the ATX treatment model, weanling rats received daily injections of either 0 mg/kg (control) or 3 mg/kg ATX via intraperitoneal injection until they reached 8 weeks old. Unlike the TCS model, ATX exposure only occurred after the pups were weaned. The results indicated that long-life TCS exposure led to attention-deficit hyperactivity disorder (ADHD)-like behaviors in male offspring rats accompanied by dopamine-related mRNA and protein expression imbalances in the prefrontal cortex (PFC). Moreover, in vitro experiments also confirmed these findings. Mechanistically, TCS reduced dopamine (DA) synthesis, release, and transmission, and increased reuptake in PFC, thereby reducing synaptic gap DA levels and causing dopaminergic deficits. Additional experiments revealed that increased DA concentration in PFC by ATX effectively alleviated TCS-induced ADHD-like behavior in male offspring rats. These findings suggest that long-life TCS exposure causes ADHD-like behavior in male offspring rats through dopaminergic deficits. Furthermore, ATX treatment not only reduce symptoms in the rats, but also reveals valuable insights into the neurotoxic mechanisms induced by TCS.

Abstract Background Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition. Methods A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test). Results Patients with BD showed significant cognitive impairment (p

Abstract Background Bipolar disorder (BD) is a severe mental disorder with heavy disease burden. Females with BD are special populations who suffer a lot from childhood trauma, social support, cognitive deficits, and suicidality. In this study, the relationship among childhood trauma, social support, and clinical symptoms of BD was investigated and the risk factors for suicidality were explored in female patients with BD. Methods This study included 57 drug-naive female BD patients, 64 female BD patients with long-term medication, and 50 age-matched female healthy controls. Childhood trauma, social support, clinical symptoms, cognition, and suicidality (suicide ideation, suicide plan, suicide attempt, suicide frequency) were measured with scales. Results Compared with healthy controls, females with BD showed higher levels of childhood trauma and suicidality, and lower levels of social support and cognitive deficits. In the drug-naïve BD group, social support mediated the relationship between childhood trauma and insomnia symptoms (indirect effect: ab = 0.025). In the BD with long-term medication group, mania symptom was associated with suicide plan (OR = 1.127, p = 0.030), childhood trauma was associated with suicide attempt (OR = 1.088, p = 0.018), and years of education (OR = 0.773, p = 0.028), childhood trauma (OR = 1.059, p = 0.009), and delayed memory (OR= 1.091, p= 0.016) was associated with suicide frequency (OR = 1.091, p = 0.016). Conclusions This study provides initial evidence that social support partially explains the relationship between childhood trauma and clinical symptoms in females with BD. Additionally, mania symptoms, childhood trauma, and delayed memory were risk factors for suicidality. Interventions providing social support and improving cognitive function may be beneficial for females with BD who are exposed to childhood trauma and with high suicide risk.

Summary: Background: The prevalence of metabolic-associated steatotic liver disease (MASLD) is rising precipitously among children, particularly in regions or countries burdened with high prevalence of obesity. However, identifying those at high risk remains a significant challenge, as the majority do not exhibit distinct symptoms of MASLD. There is an urgent need for a widely accepted non-invasive predictor to facilitate early disease diagnosis and management of the disease. Our study aims to 1) evaluate and compare existing predictors of MASLD, and 2) develop a practical screening strategy for children, tailored to local prevalence of obesity. Methods: We utilized a school-based cross-sectional survey in Beijing as the training dataset to establish predictive models for screening MASLD in children. An independent school-based study in Ningbo was used to validate the models. We selected the optimal non-invasive MASLD predictor by comparing logistic regression model, random forest model, decision tree model, and support vector machine model using both the Beijing and Ningbo datasets. This was followed by serial testing using the best performance index we identified and indices from previous studies. Finally, we calculated the potential MASLD screening recommendation categories and corresponding profits based on national and subnational obesity prevalence, and applied those three categories to 200 countries according to their obesity prevalence from 1990 to 2022. Findings: A total of 1018 children were included (NBeijing = 596, NNingbo = 422). The logistic regression model demonstrated the best performance, identifying the waist-to-height ratio (WHtR, cutoff value ≥0.48) as the optimal noninvasive index for predicting MASLD, with strong performance in both training and validation set. Additionally, the combination of WHtR and lipid accumulation product (LAP) was selected as an optimal serial test to improve the positive predictive value, with a LAP cutoff value of ≥668.22 cm × mg/dL. Based on the obesity prevalence among 30 provinces, three MASLD screening recommendations were proposed: 1) “Population-screening-recommended”: For regions with an obesity prevalence ≥12.0%, where MASLD prevalence ranged from 5.0% to 21.5%; 2) “Resources-permitted”: For regions with an obesity prevalence between 8.4% and 12.0%, where MASLD prevalence ranged from 2.3% to 4.4%; 3) “Population-screening-not-recommended”: For regions with an obesity prevalence

Abstract Background The relationship between lean body mass (LBM) and blood pressure (BP) is controversial and limited. This study investigated the associations between LBM indexes and BP in adults of different ages and with varying body fat distribution. Methods The data for the present analysis was obtained from a cross-sectional survey of 1,465 adults (50.7% males) aged 18–70 years conducted in Beijing, China. Regional LBM and fat distribution, including fat mass (FM) and android to gynoid fat ratio (AOI), were assessed using a dual-energy X-ray bone densitometer. Generalized Liner Model (GLM) was employed. Confounders, including age, sex, height, weight, smoking, and alcohol use, were evaluated through questionnaires and physical examinations. Results Males had higher rates of hypertension (11.19% vs. 4.92%) and prehypertension (21.57% vs. 14.59%) than females. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 122.04 mmHg and 76.68 mmHg. There were no significant associations between LBM and DBP (p > 0.05). However, arms LBM (β = 1.86, 95% CI: 0.77, 2.94) and trunk LBM (β = 0.37, 95% CI: 0.01, 0.73) were significantly associated with SBP. The association of LBM on DBP was stronger with increasing ages, and stronger in females than in males (p

BackgroundBeyond the direct effect of COVID-19 infection on young people, the wider impact of the pandemic on other infectious diseases remains unknown. ObjectiveThis study aims to assess changes in the incidence and mortality of 42 notifiable infectious diseases during the pandemic among children and adolescents in China, compared with prepandemic levels. MethodsThe Notifiable Infectious Disease Surveillance System of China was used to detect new cases and fatalities among individuals aged 5-22 years across 42 notifiable infectious diseases spanning from 2018 to 2021. These infectious diseases were categorized into 5 groups: respiratory, gastrointestinal and enterovirus, sexually transmitted and blood-borne, zoonotic, and vector-borne diseases. Each year (2018-2021) was segmented into 4 phases: phase 1 (January 1-22), phase 2 (January 23-April 7), phase 3 (April 8-August 31), and phase 4 (September 1-December 31) according to the varying intensities of pandemic restrictive measures in 2020. Generalized linear models were applied to assess the change in the incidence and mortality within each disease category, using 2018 and 2019 as the reference. ResultsA total of 4,898,260 incident cases and 3701 deaths were included. The overall incidence of notifiable infectious diseases decreased sharply during the first year of the COVID-19 pandemic (2020) compared with prepandemic levels (2018 and 2019), and then rebounded in 2021, particularly in South China. Across the past 4 years, the number of deaths steadily decreased. The incidence of diseases rebounded differentially by the pandemic phase. For instance, although seasonal influenza dominated respiratory diseases in 2019, it showed a substantial decline during the pandemic (percent change in phase 2 2020: 0.21, 95% CI 0.09-0.50), which persisted until 2021 (percent change in phase 4 2021: 1.02, 95% CI 0.74-1.41). The incidence of gastrointestinal and enterovirus diseases decreased by 33.6% during 2020 but rebounded by 56.9% in 2021, mainly driven by hand, foot, and mouth disease (percent change in phase 3 2021: 1.28, 95% CI 1.17-1.41) and infectious diarrhea (percent change in phase 3 2020: 1.22, 95% CI 1.17-1.28). Sexually transmitted and blood-borne diseases were restrained during the first year of 2021 but rebounded quickly in 2021, mainly driven by syphilis (percent change in phase 3 2020: 1.31, 95% CI 1.23-1.40) and gonorrhea (percent change in phase 3 2020: 1.10, 95% CI 1.05-1.16). Zoonotic diseases were not dampened by the pandemic but continued to increase across the study period, mainly due to brucellosis (percent change in phase 2 2020: 0.94, 95% CI 0.75-1.16). Vector-borne diseases showed a continuous decline during 2020, dominated by hemorrhagic fever (percent change in phase 2 2020: 0.68, 95% CI 0.53-0.87), but rebounded in 2021. ConclusionsThe COVID-19 pandemic was associated with a marked decline in notifiable infectious diseases in Chinese children and adolescents. These effects were not sustained, with evidence of a rebound to prepandemic levels by late 2021. To effectively address the postpandemic resurgence of infectious diseases in children and adolescents, it will be essential to maintain disease surveillance and strengthen the implementation of various initiatives. These include extending immunization programs, prioritizing the management of sexually transmitted infections, continuing feasible nonpharmaceutical intervention projects, and effectively managing imported infections.

BackgroundAn accelerated epidemiological transition, spurred by economic development and urbanization, has led to a rapid transformation of the disease spectrum. However, this transition has resulted in a divergent change in the burden of infectious diseases between urban and rural areas. The objective of our study was to evaluate the long-term urban-rural disparities in infectious diseases among children, adolescents, and youths in China, while also examining the specific diseases driving these disparities.Methods and findingsThis observational study examined data on 43 notifiable infectious diseases from 8,442,956 cases from individuals aged 4 to 24 years, with 4,487,043 cases in urban areas and 3,955,913 in rural areas. The data from 2013 to 2021 were obtained from China's Notifiable Infectious Disease Surveillance System. The 43 infectious diseases were categorized into 7 categories: vaccine-preventable, bacterial, gastrointestinal and enterovirus, sexually transmitted and bloodborne, vectorborne, zoonotic, and quarantinable diseases. The calculation of infectious disease incidence was stratified by urban and rural areas. We used the index of incidence rate ratio (IRR), calculated by dividing the urban incidence rate by the rural incidence rate for each disease category, to assess the urban-rural disparity. During the nine-year study period, most notifiable infectious diseases in both urban and rural areas exhibited either a decreased or stable pattern. However, a significant and progressively widening urban-rural disparity in notifiable infectious diseases was observed. Children, adolescents, and youths in urban areas experienced a higher average yearly incidence compared to their rural counterparts, with rates of 439 per 100,000 compared to 211 per 100,000, respectively (IRR: 2.078, 95% CI [2.075, 2.081]; p < 0.001). From 2013 to 2021, this disparity was primarily driven by higher incidences of pertussis (IRR: 1.782, 95% CI [1.705, 1.862]; p < 0.001) and seasonal influenza (IRR: 3.213, 95% CI [3.205, 3.220]; p < 0.001) among vaccine-preventable diseases, tuberculosis (IRR: 1.011, 95% CI [1.006, 1.015]; p < 0.001), and scarlet fever (IRR: 2.942, 95% CI [2.918, 2.966]; p < 0.001) among bacterial diseases, infectious diarrhea (IRR: 1.932, 95% CI [1.924, 1.939]; p < 0.001), and hand, foot, and mouth disease (IRR: 2.501, 95% CI [2.491, 2.510]; p < 0.001) among gastrointestinal and enterovirus diseases, dengue (IRR: 11.952, 95% CI [11.313, 12.628]; p < 0.001) among vectorborne diseases, and 4 sexually transmitted and bloodborne diseases (syphilis: IRR 1.743, 95% CI [1.731, 1.755], p < 0.001; gonorrhea: IRR 2.658, 95% CI [2.635, 2.682], p < 0.001; HIV/AIDS: IRR 2.269, 95% CI [2.239, 2.299], p < 0.001; hepatitis C: IRR 1.540, 95% CI [1.506, 1.575], p < 0.001), but was partially offset by lower incidences of most zoonotic and quarantinable diseases in urban areas (for example, brucellosis among zoonotic: IRR 0.516, 95% CI [0.498, 0.534], p < 0.001; hemorrhagic fever among quarantinable: IRR 0.930, 95% CI [0.881, 0.981], p = 0.008). Additionally, the overall urban-rural disparity was particularly pronounced in the middle (IRR: 1.704, 95% CI [1.699, 1.708]; p < 0.001) and northeastern regions (IRR: 1.713, 95% CI [1.700, 1.726]; p < 0.001) of China. A primary limitation of our study is that the incidence was calculated based on annual average population data without accounting for population mobility.ConclusionsA significant urban-rural disparity in notifiable infectious diseases among children, adolescents, and youths was evident from our study. The burden in urban areas exceeded that in rural areas by more than 2-fold, and this gap appears to be widening, particularly influenced by tuberculosis, scarlet fever, infectious diarrhea, and typhus. These findings underscore the urgent need for interventions to mitigate infectious diseases and address the growing urban-rural disparity.

Triclosan (TCS) is a widely used synthetic, with broad-spectrum antibacterial properties found in both pharmaceuticals and personal care products. More specifically, it is hepatotoxic in rodents and exhibits differential effects in mice and humans. However, the mechanisms underlying TCS-induced liver toxicity have not been elucidated. This study examined the role of the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB)/ nod-like receptor protein 3 (NLRP3) pathway in TCS-exposed liver toxicity by established a long-life TCS-exposed mice liver injury model. The 24 C57BL/6 pregnant mice exposed to TCS (0, 50 and 100 mg/kg) every day during the gestation and nursing period. After weaning, the male mice were left to continue administrate with TCS until 8 weeks of age. Then, mice in each group were sacrificed for investigation. Long-life exposure to TCS resulted in a reduction of body weight in growth mice. TCS exposure caused the increase of serum ALT, AST and ALP. The situation of inflammatory cell infiltration, macrophage recruitment and collagen fiber deposition in TCS-exposed mice liver tissues were performed by histological analysis including hematoxylin-eosin, Masson, Sirius red, and immunohistochemistry staining. Protein expression levels in TLR4/NF-κB/NLRP3 pathway was measured through Western blot, and the NLRP3 inflammasome activation was measured using real-time quantitative PCR (RT-qPCR). The results showed that exposure to TCS elevated TLR4, myeloid differentiation factor 88 (Myd88), TNF receptor associated factor 6 (TRAF6), enhanced NF-κB activation, and affected NLRP3 inflammasome activation in mice liver. Collectively, these findings indicate that long-life exposure to TCS-induced mice by upregulating the TLR4-Myd88-TRAF6 pathway, activating the NF-κB signaling cascade, initiating the NLRP3 inflammasome pathway, and ultimately leading to liver injury, including inflammation, hepatocyte pyroptosis and hepatofibrosis. Henceforth, the TLR4/NF-κB/NLRP3 pathway may now provide a theoretical basis and valuable therapeutic targets for overcoming TCS-induced liver toxicity.

Abstract Background Phthalate esters (PAEs) are known to have hormone-like properties, and there is a growing trend of children expressing a gender identity different from assigned sex. However, there has been limited research in the potential links between PAEs exposure and gender identity. Methods A total of 571 children (278 boys) completed the follow-up from Oct 2017 to Oct 2020 in Childhood Blood Pressure and Environmental Factors (CBPEF) cohort in Xiamen, China. Urinary PAE metabolites were measured at three time of visits using ultraperformance liquid chromatography-tandem mass spectrometry. The Children’s Sex Role Inventory scale was used to assess gender identity (masculinity, femininity, androgyny and undifferentiated), and Tanner definition was used to define puberty timing. Generalized linear models and log-binomial regression were used to assess the relationships between PAEs exposure, gender trait scores and gender identity. Results Overall, the concentration of most PAEs in more than 90% of participants was above the limit of detection values. In visit 1, there were 10.1% boys with femininity and 11.3% girls with masculinity; while these figures increased to 10.8% and 12.3% during follow-up, respectively. Early puberty onset accounted for 24.8% and 25.6% among boys and girls. Long-term exposure to mono-2-ethylhexyl phthalate (MEHP) (β = 1.20, 95%CI = 0.13, 2.28), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (β = 1.25, 95%CI = 0.22, 2.28) and mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 1.40, 95%CI = 0.24, 2.56) was associated with the increased differences of femininity trait scores in boys who enter puberty earlier, prolonged exposure to di(2-ethylhexyl) phthalate (DEHP) might also have such a positive impact (β = 1.38, 95%CI = 0.36, 2.41). For gender identity, persistent exposure to low molecular weight phthalates (LMWP) was negatively associated with undifferentiated type among boys entering puberty earlier (RR = 0.18, 95%CI = 0.05, 0.75, P 1 for their femininity. Conclusion Long-term exposure to PAEs increase the femininity trait scores in boys with early onset of puberty. Although the mechanisms remain to be determined, environmental pollution might have subtle, yet measurable effects on childhood gender identity. Reducing these chemicals exposure has important public implications on gender development.

Abstract Background This study aimed to compare the diagnostic efficiency of Ovarian-Adnexal Reporting and Data System (O-RADS) and doctors’ subjective judgment in diagnosing the malignancy risk of adnexal masses. Methods This was an analysis of 616 adnexal masses between 2017 and 2020. The clinical findings, preoperative ultrasound images, and pathological diagnosis were recorded. Each adnexal mass was evaluated by doctors’ subjective judgment and O-RADS by two senior doctors and two junior doctors. A mass with an O-RADS grade of 1 to 3 was a benign tumor, and a mass with an O-RADS grade of 4–5 was a malignant tumor. All outcomes were compared with the pathological diagnosis. Results Of the 616 adnexal masses, 469 (76.1%) were benign, and 147 (23.9%) were malignant. There was no difference between the area under the curve of O-RADS and the subjective judgment for junior doctors (0.83 (95% CI: 0.79–0.87) vs. 0.79 (95% CI: 0.76–0.83), p = 0.0888). The areas under the curve of O-RADS and subjective judgment were equal for senior doctors (0.86 (95% CI: 0.83–0.89) vs. 0.86 (95% CI: 0.83–0.90), p = 0.8904). O-RADS had much higher sensitivity than the subjective judgment in detecting malignant tumors for junior doctors (84.4% vs. 70.1%) and senior doctors (91.2% vs. 81.0%). In the subgroup analysis for detecting the main benign lesions of the mature cystic teratoma and ovarian endometriosic cyst, the junior doctors’ diagnostic accuracy was obviously worse than the senior doctors’ on using O-RADS. Conclusions O-RADS had excellent performance in predicting malignant adnexal masses. It could compensate for the lack of experience of junior doctors to a certain extent. Better performance in discriminating various benign lesions should be expected with some complement.

Abstract This paper investigates the adaptive robust control problem based on reinforcement learning for an affine nonlinear system with unknown time‐varying uncertainty. Inspired by the ability to estimate uncertainty of neural network, a novel policy iteration algorithm is proposed which alternates between the value evaluation, uncertainty estimation, and policy update steps until the adaptive robust control law is obtained. Especially during the step of uncertainty estimation, the unknown time‐varying uncertainty is approximated by a radial basis function neural network and introduce it into the reinforcement learning framework. By designing an appropriate utility function, the algorithm improves both convergence rate and final approximate error comparing with existing reinforcement learning algorithm. The Lyapunov stability theorem provides theoretical demonstrations of the stability and convergence. Furthermore, the uniformly ultimately bounded stability of the affine nonlinear system is demonstrated with unknown time‐varying uncertainty. Finally, the performance of the proposed algorithm is demonstrated through a torsion pendulum system.

Abstract Background Maresin-1 plays an important role in diabetic illnesses and ferroptosis is associated with pathogenic processes of diabetic retinopathy (DR). The goal of this study is to explore the influence of maresin-1 on ferroptosis and its molecular mechanism in DR. Methods ARPE-19 cells were exposed to high glucose (HG) condition for developing a cellular model of DR. The CCK-8 assay and flow cytometry were used to assess ARPE-19 cell proliferation and apoptosis, respectively. Furthermore, the GSH content, MDA content, ROS level, and Fe2+ level were measured by using a colorimetric GSH test kit, a Lipid Peroxidation MDA Assay Kit, a DCFH-DA assay and the phirozine technique, respectively. Immunofluorescence labelling was used to detect protein levels of ACSL4 and PTGS2. Messenger RNA and protein expression of HO-1, GPX4 and Nrf2 was evaluated through western blotting and quantitative real time-polymerase chain reaction (qRT-PCR). To establish a diabetic mouse model, mice were intraperitoneally injected 150 mg/kg streptozotocin. The MDA content, ROS level and the iron level were detected by using corresponding commercial kits. Results Maresin-1 promoted cell proliferation while reducing the apoptotic process in HG-induced ARPE-19 cells. Maresin-1 significantly reduced ferroptosis induced by HG in ARPE-19 cells, as demonstrated as a result of decreased MDA content, ROS level, Fe2+ level, PTGS2 expression, ACSL4 expression and increased GSH content. With respect to mechanisms, maresin-1 treatment up-regulated the mRNA expression and protein expression of HO-1, GPX4 and Nrf2 in HG-induced ARPE-19 cells. Nrf2 inhibitor reversed the inhibitory effects of maresin-1 on ferroptosis in HG-induced ARPE-19 cells. In vivo experiments, we found that Maresin-1 evidently repressed ferroptosis a mouse model of DR, as evidenced by the decreased MDA content, ROS level and iron level in retinal tissues of mice. Conclusion Maresin-1 protects ARPE cells from HG-induced ferroptosis via activating the Nrf2/HO-1/GPX4 pathway, suggesting that maresin-1 prevents DR development.

The estimation of Unmanned Aerial Vehicle (UAV) poses using visual information is essential in Global Navigation Satellite System (GNSS)-denied environments. In this paper, we propose a UAV visual navigation algorithm based on visual-geography Bundle Adjustment (BA) to address the challenge of missing geolocation information in monocular visual navigation. This algorithm presents an effective approach to UAV navigation and positioning. Initially, Visual Odometry (VO) was employed for tracking the UAV’s motion and extracting keyframes. Subsequently, a geolocation method based on heterogeneous image matching was utilized to calculate the geographic pose of the UAV. Additionally, we introduce a tightly coupled information fusion method based on visual-geography optimization, which provides a geographic initializer and enables real-time estimation of the UAV’s geographical pose. Finally, the algorithm dynamically adjusts the weight of geographic information to improve optimization accuracy. The proposed method is extensively evaluated in both simulated and real-world environments, and the results demonstrate that our proposed approach can accurately and in real-time estimate the geographic pose of the UAV in a GNSS-denied environment. Specifically, our proposed approach achieves a root-mean-square error (RMSE) and mean positioning accuracy of less than 13 m.

Abstract Objective: The relationships between childhood weight self-misperception and obesity-related factors particularly health markers have not been extensively discussed. This study aims to examine the associations between weight self-misperception and obesity-related knowledge, attitudes, lifestyles and cardio-metabolic markers among Chinese paediatric population. Design: Cross-sectional study. Setting: Data sourced from a national survey in Chinese seven provinces in 2013. Participants: Children and adolescents aged 5–19 years. Results: Of the total 14 079 participants, there were 14·5 % and 2·2 % participants over-estimated and under-perceived their weight, respectively. Multi-variable logistic regression was applied to calculate OR and 95 % CI (95 % Cl) of obesity-related behaviours and cardio-metabolic markers by actual and perceived weight status. Individuals who perceived themselves as overweight/obese were more likely to have prolonged screen time, insufficient dairy intake and over sugar-sweetened beverages consumption (all P < 0·05), regardless of their weight. Furthermore, actual overweight/obese individuals had higher odds of abnormal cardio-metabolic markers, but a smaller magnitude of association was found among weight under-estimators. Among non-overweight/obese individuals, weight over-estimation was positively associated with abdominal obesity (OR: 10·49, 95 % CI: 7·45, 14·76), elevated blood pressure (OR: 1·30, 95 % CI: 1·12, 1·51) and dyslipidemia (OR: 1·43, 95 % CI: 1·29, 1·58). Conclusions: Weight over-perception was more prevalent than under-estimation, particularly in girls. Weight over-estimators tended to master better knowledge but behave more unhealthily; both weight over-perception and actual overweight/obesity status were associated with poorer cardio-metabolic markers. Future obesity intervention programmes should additionally pay attention to the population with inaccurate estimation of weight who were easily overlooked.

Abstract Background Myopia and obesity in children and adolescents have become serious public health problems that endanger public health, especially in China. Unhealthy lifestyle behaviors are environmental drivers of both myopia and obesity. This protocol describes a study to evaluate the effectiveness of “22510SS”, that is 2 h of daytime outdoor activities (‘2’); Limit screen time to no more than 2 h per day (‘2’); Consume at least 5 servings of fruits and vegetables daily (‘5’); Attain 1 h of physical activity daily (‘1’); Consume 0 sugar-sweetened beverages (‘0’); Reasonable sleep duration (‘S’); Regular supervision (‘S’). A school-based, multifaceted intervention strategy for myopia and obesity prevention, and to assess and explore the implementation of “22510SS” with regards to acceptability, feasibility, adoption, usage and maintenance. Methods and analysis This study aims to develop a comprehensive intervention strategy "22510SS" based on the socio-ecological model, and A two-arm cluster randomized trial with a parallel-group of a 1:1 allocation ratio in 36 primary and secondary schools to test its evidence-based intervention programs on the effects and implementation of myopia and obesity epidemics in children and adolescents in grades 4 and 7. The primary outcomes will include differences in visual acuity, body mass index, outdoor activity indicators, screen time, fruit and vegetable intake, high-quality protein intake, sugar-sweetened beverage intake, sleep duration, and level of monitoring among children and adolescents. Secondary outcomes will assess the acceptability, feasibility, uptake, use, and maintenance of the intervention. Effects on the primary and secondary outcomes will be analyzed using linear and logistic regression analyses, as well as difference-in-difference analysis, taking into account cluster effects and possible confounding factors. Process assessments will also be conducted through quantitative and qualitative analyses, including acceptability, feasibility, gender, adoption, implementation, and sustainability. Discussion This study will evaluate the effectiveness of “22510SS” and examine its implementation in the school-based network nesting family and clinic. Following this intervention study, the integrated intervention program focused on myopia and obesity among children and adolescents have great potential to be implemented in China to promote and support healthy lifestyle behavior change and reduce the risk of myopia and obesity in children and adolescents. Trial registration NCT05275959. Registered 23 Mach 2022.

Abstract Background Infectious diseases pose a significant risk to the health and well-being of children and adolescents, and can even be life-threatening. Thus, our study aimed to explore the effectiveness of health education based on the social-ecological model in improving the knowledge of infectious diseases among this vulnerable population. Methods This study was a school-based intervention conducted in seven Chinese provinces in 2013, involving a total of 26,591 children and adolescents in the intervention group and 24,327 in the control group. The intervention group received a comprehensive health intervention based on the social-ecological model (SEM) over six months, which included a supportive environment, health education on infectious diseases, guidance on self-monitoring infectious disease-related behaviors, and other measures. Data on infectious disease-related knowledge and other characteristics were collected through questionnaires. The main outcome measure will be the difference in the effectiveness of health education regarding infectious diseases in children and adolescents between baseline and post-intervention. A mixed-effects regression model was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to assess the impact of infectious disease-related interventions on the participants. Results We utilized a socioecological model as the foundation for a six-month health education program on infectious diseases targeting children and adolescents in the intervention group. At the individual and community levels, the correct rate of health behavior related to infectious diseases in the intervention group was higher than that in the control group (P

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Ischemia-reperfusion (I/R) injury is considered the most common contributor to AMI. Hirsutine has been shown to protect cardiomyocytes against hypoxic injury. The present study investigated whether hirsutine improved AMI induced by I/R injury and the underlying mechanisms. In our study, we used a rat model of myocardial I/R injury. The rats were given hirsutine daily (5, 10, 20 mg/kg) by gavage for 15 days before the myocardial I/R injury. Detectable changes were observed in myocardial infarct size, mitochondrial function, histological damage, and cardiac cell apoptosis. According to our findings, hirsutine pre-treatment reduced the myocardial infarct size, enhanced cardiac function, inhibited cell apoptosis, reduced the tissue lactate dehydrogenase (LDH) and reactive oxygen species (ROS) content, as well as enhanced myocardial ATP content and mitochondrial complex activity. In addition, hirsutine balanced mitochondrial dynamics by increasing Mitofusin2 (Mfn2) expression while decreasing dynamin-related protein 1 phosphorylation (p-Drp1), which was partially regulated by ROS and calmodulin-dependent protein kinase II phosphorylation (p-CaMKII). Mechanistically, hirsutine inhibited mitochondrial-mediated apoptosis during I/R injury by blocking the AKT/ASK-1/p38 MAPK pathway. This present study provides a promising therapeutic intervention for myocardial I/R injury.

Abstract Background Endoplasmic reticulum stress (ER stress) may destroy endoplasmic reticulum homeostasis (ER homeostasis) and leads to programmable cell death. Unfolded protein response (UPR) originally stimulated by ER stress is critical for the survival of tumor cells through trying to re-establish ER homeostasis as an adaption to harsh microenvironment. However, mechanisms involving key regulators in modulating UPR remain underexplored. Methods The expression of LINP1 in cutaneous squamous cell carcinoma (cSCC) tissues and cell lines was assessed. Subsequently, LINP1 was knocked out, knocked down or overexpressed in cSCC cells. CCK-8 assays, colony forming assays, transwell migration assays and invasiveness measurement by matrigel-coated transwell were performed to examine the role of LINP1 in cSCC development through gain-of-function and loss-of-function experiments. Transcriptomic sequencing (RNA-Seq) was conducted and indicated the key downstream signaling events regulated by LINP1 including UPR and apoptosis signaling. Furthermore, the direct interaction between LINP1 and eIF2α to modulate UPR and apoptosis was confirmed by RNA pulldown, RNA immunoprecipitation (RIP), ChIP-qPCR and in vitro phosphorylation assays. Results In this study, LncRNA in non-homologous end joining pathway 1 (LINP1) was identified to be one of the top ten highest-expressed LncRNAs in cSCC, the second most common cancer in the world. Functional studies using in vitro and in vivo models revealed that LINP1 functions as an oncogene to promote cell proliferation, colony formation, migration and invasiveness while inhibiting cell apoptosis in cSCC. Transcriptomic sequencing after knockdown of LINP1 indicated LINP1 negatively regulates UPR-related pathways involving key effectors for activating UPR and the apoptosis following the prolonged UPR. Mechanistic study showed LINP1 physically interacts with eIF2α to inhibit its phosphorylation for avoiding unmitigated UPR. Loss of LINP1 followed by enhanced eIF2α phosphorylation led to overactivated UPR and induced DDIT3 expression, contributing to ER stress-induced apoptosis and suppression of cSCC development. Conclusions Our findings demonstrate a novel regulatory hierarchy of UPR by demonstrating LINP1 as a critical modulator for eIF2α phosphorylation and a suppressor of UPR-mediated apoptosis, which suggests a novel therapeutic target for cSCC treatment.

Currently, many fault diagnosis methods for rolling bearings based on deep learning are facing two main challenges. Firstly, the deep learning model exhibits poor diagnostic performance and limited generalization ability in the presence of noise signals and varying loads. Secondly, there is incomplete utilization of fault information and inadequate extraction of fault features, leading to the low diagnostic accuracy of the model. To address these problems, this paper proposes an improved dual-branch convolutional capsule neural network for rolling bearing fault diagnosis. This method converts the collected bearing vibration signals into grayscale images to construct a grayscale image dataset. By fully considering the types of bearing faults and damage diameters, the data are labeled using a dual-label format. A multi-scale convolution module is introduced to extract features from the data and maximize feature information extraction. Additionally, a coordinate attention mechanism is incorporated into this module to better extract useful channel features and enhance feature extraction capability. Based on adaptive fusion between fault type (damage diameter) features and labels, a dual-branch convolutional capsule neural network model for rolling bearing fault diagnosis is established. The model was experimentally validated using both Case Western Reserve University’s bearing dataset and self-made datasets. The experimental results demonstrate that the fault type branch of the model achieves an accuracy rate of 99.88%, while the damage diameter branch attains an accuracy rate of 99.72%. Both branches exhibit excellent classification performance and display robustness against noise interference and variable working conditions. In comparison with other algorithm models cited in the reference literature, the diagnostic capability of the model proposed in this study surpasses them. Furthermore, the generalization ability of the model is validated using a self-constructed laboratory dataset, yielding an average accuracy rate of 94.25% for both branches.

Droughts have a severe impact on the environment and social economy, and predicting their future changes is challenging due to significant uncertainties in climate change and human activities. Many countries have pledged to achieve carbon neutrality to limit global warming; however, few studies have focused on drought changes during the carbon-neutral period. Here, we analyzed the variations in drought characteristics across the Yellow River Basin (YRB) during the carbon-neutral period under two low-emission scenarios from 7 CMIP6 model outputs. The results show that the temperature and precipitation will increase significantly during the 2015–2100 period under both SSP1-1.9 and SSP1-2.6 scenarios. Compared to the historical period (1979–2014), the hydrological drought frequency is projected to decrease by 15.5% (13.0–18.1%), while drought severity is expected to increase by 14.4% (13.2–15.7%) during the carbon-neutral period. Meteorological droughts exhibit a similar changing trend, although the results vary between different regions. In general, more severe hydrological droughts may occur in the southern YRB in the carbon-neutral period under low-emission scenarios. This study has implications for future drought mitigation within the Yellow River Basin.

The effects of Helicobacter pylori eradication on gastric mucosa-colonizing microbes in patients with functional dyspepsia (FD) remain unclear. Here, we explored microbial variation induced by H. pylori infection and eradication treatment in FD patients. Gastric microbial abundance and diversity were significantly reduced in the H. pylori-infected FD patients. Eradication treatment increased alpha and beta diversity of gastric mucosa-colonizing microbes, and promoted the expansion of several probiotic microbes, such as Leuconostoc mesenteroides, which exhibited a matched antagonistic performance against H. pylori. Significant variation was observed in gastric mucosa-colonizing microbes between H. pylori-positive and H. pylori-negative FD patients. Eradication treatment induced microbial diversity recovery and may provide sufficient nutrition and space for probiotic microbes, such as Leuconostoc mesenteroides.

Background: Early onset of puberty could have significant impacts on childhood health, but the extent to which it was affected by phthalate esters (PAEs) and sex hormone disruption was not understood. The aim of this study is to investigate the associations between exposure to PAEs and sex hormone disruption and early onset of puberty in children. Methods: A longitudinal cohort study was conducted in China from May 2017 to Oct 2020, involving 740 children during consecutive visits. The onset of puberty was evaluated using Tanner definition, and early puberty was defined as an onset age less than the first 25 %, with cut-offs of 10.33 and 8.97 years for boys and girls, respectively. Serum testosterone (TT), estradiol (E2) and urinary PAE metabolites were measured during three visits. Generalized linear models were used to explore the associations between PAE and sex hormones with the age of puberty onset, while log-binomial regressions were applied to assess the associations of persistent exposure to PAEs and sex hormones with early pubertal onset. Results: Approximately 86.0 % of boys and 90.2 % of girls completed puberty onset from pre-puberty, and more than 95 % of participants had PAE concentrations higher than the limit of detection. Boys showed higher exposure to PAE pollutants and higher TT levels. Persistent exposure to PAEs was positively associated with early pubertal onset in girls (ARR = 1.97, 95 %CI = 1.12, 3.46). Moreover, persistent exposure to PAEs and E2 had synergistic associations with early pubertal onset in both boys (ARR = 4.77, 95 %CI = 1.06, 21.54) and girls (ARR = 7.07, 95 %CI = 1.51, 33.10). However, PAEs and TT had antagonistic associations only in boys (ARR = 0.44, 95 %CI = 0.07, 2.58). Conclusion: Long-term exposure to PAEs might increase the risk of early pubertal onset, and it appears to work in synergy with E2, while in antagonism with TT in boys’ early pubertal onset. Reducing PAEs exposure might promote pubertal health.

Abstract Cutaneous radiation injury (CRI) interrupts the scheduled process of radiotherapy and even compromises the life quality of patients. However, the current clinical options for alleviating CRI are relatively limited. Resveratrol (RSV) has been shown to be a promising protective agent against CRI; yet the mechanisms of RSV enhancing radioresistance were not fully elucidated and limited its clinical application. In this study, we demonstrate RSV promotes cutaneous radioresistance mainly through SIRT7. During ionizing radiation (IR) treatment, RSV indirectly phosphorylates and activates SIRT7 through AMPK, which is critical for maintaining the genome stability of keratinocytes. Immunoprecipitation and mass spectrometry identified HMGB1 to be the key interacting partner of SIRT7 to mediate the radioprotective function of RSV. Mechanistic study elucidated that SIRT7 interacts with and deacetylates HMGB1 to redistribute it into nucleus and “switch on” its function for DNA damage repair. Our findings establish a novel AMPK/SIRT7/HMGB1 regulatory axis that mediates the radioprotective function of RSV to alleviate IR-induced cutaneous DNA injury, providing an efficiently-curative option for patients with CRI during radiotherapy.

Abstract Hypertension is an important global public health issue because of its high morbidity as well as the increased risk of other diseases. Recent studies have indicated that the development of hypertension is related to the dysbiosis of the gut microbiota in both animals and humans. In this review, we outline the interaction between gut microbiota and hypertension, including gut microbial changes in hypertension, the effect of microbial dysbiosis on blood pressure (BP), indicators of gut microbial dysbiosis in hypertension, and the microbial genera that affect BP at the taxonomic level. For example, increases in Lactobacillus, Roseburia, Coprococcus, Akkermansia, and Bifidobacterium are associated with reduced BP, while increases in Streptococcus, Blautia, and Prevotella are associated with elevated BP. Furthermore, we describe the potential mechanisms involved in the regulation between gut microbiota and hypertension. Finally, we summarize the commonly used treatments of hypertension that are based on gut microbes, including fecal microbiota transfer, probiotics and prebiotics, antibiotics, and dietary supplements. This review aims to find novel potential genera for improving hypertension and give a direction for future studies on gut microbiota in hypertension.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human β-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.

Abstract Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer and the second most fatal cancer in the world despite the great therapeutic advances in the past two decades, which reminds us of the gap in fully understanding the oncogenic mechanism of HCC. To explore the key factors contributing to the progression of HCC, we identified a LncRNA, termed SALIS (Suppression of Apoptosis by LINC01186 Interacting with STAT5A), functions in promoting the proliferation, colony formation, migration and invasion while suppressing apoptosis in HCC cells. Mechanistic study indicated SALIS physically associates with transcription factor STAT5A and binds to the promoter regions of IGFBP3 and Caspase-7 to transcriptionally repress their expression and further inhibit apoptosis. Our findings identified SALIS as an oncogene to promote HCC by physically binding with STAT5A to inhibit the expression of pro-apoptotic IGFBP3 and Caspase-7, which suggests novel therapeutic targets for HCC treatments.

Purpose This study compared the diagnostic performance of the Ovarian-Adnexal Reporting and Data System (O-RADS), the Risk of Malignancy Index 4 (RMI4), the International Ovarian of Tumor Analysis Logistic Regression Model 2 (IOTA LR2), and the IOTA Simple Rules (IOTA SR) in predicting the malignancy of adnexal masses (AMs). Methods This retrospective study included 575 women with AMs between 2017 and 2020. All clinical messages, ultrasound images, and pathological findings were collected. Two senior doctors (group I) and two junior doctors (group II) used the four systems to classify AMs. The postoperative pathological diagnosis was used as the gold standard to evaluate the diagnostic efficiency. A receiver operating characteristic curve was used to test the diagnostic performance. The interrater agreement between the two groups was tested using kappa values. Results Of all 592 AMs, 447 (75.5%) were benign, 123 (20.8%) were malignant, and 22 (3.7%) were borderline. The intergroup consistency test yielded kappa values of 0.71, 0.92, 0.68, and 0.77 for the O-RADS, RMI4, IOTA LR2, and IOTA SR, respectively. To predict malignant lesions, the areas under the curve of the O-RADS, RMI4, IOTA LR2, and IOTA SR systems were 0.90, 0.89, 0.90, and 0.86 for group I and 0.89, 0.87, 0.88, and 0.84 for group II, respectively. The O-RADS had the highest sensitivity (91.0% in group I and 84.8% in group II). Conclusion The four diagnostic systems could compensate for junior doctors’ inexperience in predicting malignant adnexal lesions. The O-RADS performed best and showed the highest sensitivity.

IntroductionWe aimed to investigate the association between greenness around schools, long-term gaseous air pollution exposure (SO2 and CO), and blood pressure in children and adolescents.MethodsFrom 2006 to 2018, a total of 219,956 Chinese children and adolescents aged 7–17 years in Beijing and Zhongshan were included in this longitudinal study. Annual average concentrations of SO2 and CO and the mean values of normalized difference vegetation index around schools were calculated. We used the generalized estimation equation model, restricted cubic spline model, and Cox model to analyze the health effects.ResultsAmong all the subjects, 52,515 had the first onset of HBP. During the follow-up, HBP's cumulative incidence and incidence density were 23.88% and 7.72 per 100 person-year respectively. Exposures to SO2 and CO were significantly associated with SBP [β = 1.30, 95% CI: (1.26, 1.34) and 0.78 (0.75, 0.81)], DBP [β = 0.81 (0.79, 0.84) and 0.46 (0.44, 0.48)] and HBP [HR = 1.58 (1.57, 1.60) and 1.42 (1.41, 1.43)]. The risks of HBP attributed to SO2 and CO pollution would be higher in school-aged children in the low greenness group: the attributable fractions (AFs) were 26.31% and 20.04%, but only 13.90% and 17.81% in the higher greenness group. The AFs were also higher for normal-BMI children and adolescents in the low greenness group (AFs = 30.90% and 22.64%, but 14.41% and 18.65% in the high greenness group), while the AFs were not as high as expected for obese children in the low greenness group (AFs = 10.64% and 8.61%), nor was it significantly lower in the high greenness group (AFs = 9.60% and 10.72%).DiscussionGreenness could alleviate the damage effects of SO2/CO exposure on the risks of HBP among children and adolescents, and the benefit is BMI sensitivity. It might offer insights for policymakers in making effective official interventions to prevent and control the prevalence of childhood HBP and the future disease burden caused by air pollution.

Acoustic neuroma is one of the most common tumors in the cerebellopontine angle area. Patients with acoustic neuroma have clinical manifestations of the cerebellopontine angle occupying syndrome, such as tinnitus, hearing impairment and even hearing loss. Acoustic neuromas often grow in the internal auditory canal. Neurosurgeons need to observe the lesion contour with the help of MRI images, which not only takes a lot of time, but also is easily affected by subjective factors. Therefore, the automatic and accurate segmentation of acoustic neuroma in cerebellopontine angle on MRI is of great significance for surgical treatment and expected rehabilitation. In this paper, an automatic segmentation method based on Transformer is proposed, using TransUNet as the core model. As some acoustic neuromas are irregular in shape and grow into the internal auditory canal, larger receptive fields are thus needed to synthesize the features. Therefore, we added Atrous Spatial Pyramid Pooling to CNN, which can obtain a larger receptive field without losing too much resolution. Since acoustic neuromas often occur in the cerebellopontine angle area with relatively fixed position, we combined channel attention with pixel attention in the up-sampling stage so as to make our model automatically learn different weights by adding the attention mechanism. In addition, we collected 300 MRI sequence nuclear resonance images of patients with acoustic neuromas in Tianjin Huanhu hospital for training and verification. The ablation experimental results show that the proposed method is reasonable and effective. The comparative experimental results show that the Dice and Hausdorff 95 metrics of the proposed method reach 95.74% and 1.9476 mm respectively, indicating that it is not only superior to the classical models such as UNet, PANet, PSPNet, UNet++, and DeepLabv3, but also show better performance than the newly-proposed SOTA (state-of-the-art) models such as CCNet, MANet, BiseNetv2, Swin-Unet, MedT, TransUNet, and UCTransNet.

BackgroundLAMA2-related limb girdle muscular dystrophy (LGMD R23) is rare. The detailed clinical phenotypes and genetic information associated with LGMD R23 are unknown.MethodsWe conducted a retrospective cross-sectional and longitudinal study on 19 LGMD R23 patients.ResultsNormal early motor development was observed in 84.2% patients. Mild orthopedic complications were observed in 42.1% patients. 36.8% patients had seizures, which is unusually frequent in LGMD. Epilepsy was eventually diagnosed in 26.3% patients. 46.7% patients presented with motor neuropathy. Genetic analysis identified 29 pathogenic variants, with missense and frameshift variants being the most common. The mutant sites were mainly distributed in the N-terminal and G-like domains of laminin. The missense variants are distributed near the N-terminus (exons 3–11), whereas frameshift variants are distributed in exons 12–65. Five patients were diagnosed with epilepsy and all of them harbor at least one missense variants in exon 4. 71.4% variants of patients with motor neuropathy located in the LN domain.ConclusionsMissense variants in exon 4 maybe correlated with epilepsy and variants in the LN domain maybe correlated with motor neuropathy in Chinese patients. Our study expands the clinical and genetic spectrum caused by LAMA2 variations and provides novel genotype-phenotype correlations of LGMD R23.

Abstract Background Congenital myopathies are a group of rare neuromuscular diseases characterized by specific histopathological features. The relationship between the pathologies and the genetic causes is complex, and the prevalence of myopathy-causing genes varies among patients from different ethnic groups. The aim of the present study was to characterize congenital myopathies with infancy onset among patients registered at our institution. Method This retrospective study enrolled 56 patients based on the pathological and/or genetic diagnosis. Clinical, histopathological and genetic features of the patients were analysed with long-term follow-up. Results Twenty-six out of 43 patients who received next-generation sequencing had genetic confirmation, and RYR1 variations (12/26) were the most prevalent. Eighteen novel variations were identified in 6 disease-causing genes, including RYR1, NEB, TTN, TNNT1, DNM2 and ACTA1. Nemaline myopathy (17/55) was the most common histopathology. The onset ages ranged from birth to 1 year. Thirty-one patients were followed for 3.83 ± 3.05 years (ranging from 3 months to 11 years). No patient died before 1 year. Two patients died at 5 years and 8 years respectively. The motor abilities were stable or improved in 23 patients and deteriorated in 6 patients. Ten (10/31) patients developed respiratory involvement, and 9 patients (9/31) had mildly abnormal electrocardiograms and/or echocardiograms. Conclusion The severity of congenital myopathies in the neonatal/infantile period may vary in patients from different ethnic groups. More concern should be given to cardiac monitoring in patients with congenital myopathies even in those with static courses.

BackgroundThe number of empty nest elderly in China has gradually increased in recent years. There is growing concern about the physical and mental health of this population as empty nest elderly are commonly at the risk of compromising health, home safety and quality of life. This study reported the health and well-being of empty nest elderly with regards to their health status, depression and satisfaction, lifestyle as compared to non-empty nest elderly in China.MethodsData was collected from the 2018 follow-up interviews of China Health and Retirement Longitudinal Survey. We included 4,630 empty nest elderly and 6,188 non-empty nest elderly. Chi-square Test and Logistic Regression were used to compare the differences between these two groups.ResultsAs compared to the non-empty nest elderly, there was higher proportion of empty nest elderly who suffered from dyslipidemia, diabetes, chronic lung diseases, heart attack (27.0% vs. 25.0%; 16.6% vs. 15.1%; 19.4% vs. 16.4%; 26.3% vs. 23.4%, P < 0.05). The empty nest elderly had higher proportion of participants who drank more than once a month (25.3% vs. 23.9%, P < 0.05), who felt satisfied with their marriage (71.6% vs. 66.2%, P < 0.001), who were satisfied with their children's relationship (85.2% vs. 83.2%, P < 0.001). However, these significances disappeared in the Logistic Regression analysis (P > 0.05).ConclusionOur study showed that significant between-group difference was found between empty nest elderly and non-empty nest elderly in their health and wellbeing. However, disappearance of such difference in the multivariable analysis may indicate improved health and wellbeing among the empty nest elderly. Even though our study still suggested the importance of improving the health, lifestyles and family dynamics of the elderly and promoting the integration of health and social care for the elderly, especially among the empty nest elderly.

BackgroundCardiovascular health (CVH) in children and adolescents, which might be largely influenced by parental behaviors, may affect the incidence of cardiovascular diseases in adulthood. However, few studies have been conducted to explore the associations between parental behaviors and CVH status of offspring in China.MethodsData were obtained from a cross-sectional survey conducted in Chinese children and adolescents aged 7–18 years old, with a total of 10,043 parent–offspring pairs included. Parental behaviors included moderate to vigorous physical activity (MVPA), dietary behaviors, and weight status. The CVH status of offspring was consulted by The American Heart Association, including seven factors. The associations between parental behaviors and CVH status of offspring were evaluated by multilevel logistic regression. Stratified analyses were conducted to explore the potential modifying influence of sociodemographic factors.ResultsMost of the offspring had five ideal CVH factors; only 21.04% had six to seven ideal CVH factors. Parental unhealthy behaviors were associated with high odds of nonideal CVH status of offspring. Parental overweight/obesity, insufficient MVPA, and unhealthy dietary behaviors could increase the odds of owning one to three ideal CVH factors in offspring, with corresponding odds ratios (ORs) (95% confidence interval) of 1.61 (1.32–1.96), 1.31 (1.10–1.56), and 2.05 (1.43–2.94), respectively. There was a dose–response relationship between parental single unhealthy behavior and the odds of nonideal CVH status in offspring (P-trend

Abstract Aimed to investigate the associations between different growth patterns with high blood pressure, and further examine the mediation effect of BMI between growth patterns and high blood pressure among children and adolescents. A total of 31581 children and adolescents aged 7–18 years were selected based on the stratified cluster sampling method. Logistics regression models were used to calculate the odds rations (ORs) and 95% confidence interval (95%CI) of the association between different growth patterns and high blood pressure. Mediation effect analyses were applied to estimate the effect of BMI on the increase of blood pressure levels in different growth patterns. In different sex and ages, compared to reference group of normal growth, blood pressure levels and prevalence of high blood pressure of the catch‐up growth were higher, but that of the catch‐down growth were lower. The prevalence of high blood pressure was 11.69%, 16.06%, and 9.68% in normal growth, catch‐up growth, and catch‐down growth, respectively. In total, compared with the normal growth pattern, the ORs (95%CI) of high blood pressure, high systolic blood pressure and high diastolic blood pressure in the catch‐up growth were 1.171(1.073,1.280), 1.110(1.001,1.230) and 1.141(1.025,1.270) (p

Abstract Uncontrolled overactivation of autophagy may lead to autophagic cell death, suppression of which is a pro-survival strategy for tumors. However, mechanisms involving key regulators in modulating autophagic cell death remain poorly defined. Here, we report a novel long noncoding RNA, p53 upregulated regulator of p53 levels (PURPL), functions as an oncogene to promote cell proliferation, colony formation, migration, invasiveness, and inhibits cell death in melanoma cells. Mechanistic studies showed that PURPL promoted mTOR-mediated ULK1 phosphorylation at Ser757 by physical interacting with mTOR and ULK1 to constrain autophagic response to avoid cell death. Loss of PURPL led to AMPK-mediated phosphorylation of ULK1 at Ser555 and Ser317 to over-activate autophagy and induce autophagic cell death. Our results identify PURPL as a key regulator to modulate the activity of autophagy initiation factor ULK1 to repress autophagic cell death in melanoma and may represent a potential intervention target for melanoma therapy.

Based on traditional 3-D multi-component NS(Navier-stokes) equations, with chemical reaction Preconditioning method was analyzed and the preconditioning matrix was applied for the pseudo-time derivative term of the equations. Preconditioned AUSM+-up scheme was used for space discretization, with implicit time integration LU-SGS (Lower-Upper Symmetric Gauss-Seidel). These two schemes were combined to develop a unified algorithm for flows at all speeds. In addition, Numerical experiments of flows from low speed to high speed, with and without chemical reaction, were performed in this paper. By comparing the results of simulations with experiments showed the algorithm utilized the imposed preconditioning matrix, obtained better results. It was fairly well demonstrated that the improved methods can be applied efficiently for chemical reacting flow at all speeds.

BackgroundThis study investigated the associations between behavioral health risk factors (anxiety, depression, stress, insomnia, drinking, smoking) and abnormal eating attitudes among Chinese vocational high school students (CVHSS). Potential moderating relationships were also explored with relevant socio-demographic factors of the student's age, sex, rural or urban community, household income, family type and educational level of the father and mother.MethodsA total of 7,984 students from three vocational high schools in Hunan, China completed a questionnaire about their socio-demographic characteristics, alcohol use, smoking, and symptoms of depression, anxiety, stress (21-item version of the Depression Anxiety Stress Scale), insomnia (8-item Athens Insomnia Scale), and abnormal eating attitudes (19-item Chinese version of Eating Attitudes Test).ResultsThe prevalence rates for behavioral health problems among these students ranged widely depending on the risk factor: 42.5% insomnia, 41.3% anxiety, 26.2% depression, 14.4% stress, 13.7% drinking, and 8.3% smoking. Additionally, 61.7% of students were at-risk for at least one of these six behavioral health disorders. Abnormal eating attitudes were associated with depression (r = 0.422), anxiety (r = 0.490), stress (r = 0.490), and insomnia (r = 0.375), with all of these relationships being significant (p < 0.01) and large size statistical effects. However, other analyzes found that none of the socio-demographic background factors had meaningful associations with the behavioral health risk factors (0 of 28 tests) and very few background factors were associated with the abnormal eating attitude measures (only 3 of 35 tests). Females had higher levels than males on dieting and bulimia but not on the other two eating attitude components.ConclusionsThis study determined that behavioral health risk factors (sleep problems and anxiety in particular) were common among high school students in China and that mental health and sleep disorder risks also tended to co-occur in some students with abnormal eating attitudes. Therefore, prevention and early identification programs for behavioral risk factors are needed for this population. It is important to pay more attention to students with abnormal eating attitude-related symptoms, who may have also underlying mental health problems and need further evaluation.

Background: The structural similarity between sex hormones and exogenous phthalates (PAEs) enabled them as disrupters in regulating childhood blood pressure (BP). We aim to explore the association of sex hormones homeostasis and PAEs metabolites with childhood high BP (HBP). Methods: A cohort study was conducted with 1416 children aged 7–13 years at baseline and with 824, 819, and 801 children completing three waves' follow up. Serum testosterone (TT) and estradiol (E2) in children during three consecutive waves of surveys were measured by radioimmunoassay, and then TT/E2 ratio calculated as TT divided by E2 were used to represent sex hormones homeostasis. Seven urinary PAEs metabolites were measured in children of first wave. The BP Z-Scores and HBP across waves were obtained by sex, age, and height specific percentiles. Log-binomial regression models with adjusted risk ratios (aRR) after adjusting for confounders were utilized. Results: The prevalence of HBP at the baseline survey was 25.5%, and increased from 26.3% in the first wave of survey to 35.0% in the third wave of survey. PAEs were negatively correlated with E2, while positively correlated with TT and TT/E2 ratio. A positive association of the serum TT levels, TT/E2 ratio, and total PAEs was found with HBP prevalence (in wave 1, 2 and 3 with TT (aRR): 1.63, 1.37 and 1.45; with TT/E2: 1.63, 1.42 and 1.20; with PAEs: 1.40, 1.32 and 1.32), persistent HBP (with TT (aRR): 2.19; TT/E2: 2.16; PAEs: 2.57), occasional HBP (with TT (aRR): 1.94; TT/E2: 1.72; PAEs: 1.38), and new HBP incidence (with TT (aRR): 1.44; TT/E2: 1.57; PAEs: 1.67), but E2 had a negative association with HBP phenotypes (HBP prevalence in wave 1, 2 and 3 (aRR): 0.77, 0.93, and 1.10; persistent HBP: 0.47; occasional HBP: 0.96; new HBP incidence: 0.81). The E2 and PAEs had antagonistic effects on HBP risks in children, particularly in girls and those with high BMI group, but the TT levels, TT/E2 ratio and PAEs had synergistic effects on HBP risks in children, particularly in boys and those with high BMI group. Conclusion: Exogenous PAEs exposure and endogenous sex hormones homeostasis disruption independently increase the risks of HBP. Moreover, the exogenous PAEs exposure could disrupt the endogenous sex hormones homeostasis in children, thereby combinedly increased risks of childhood HBP.

Hypertension is a major threat to human health. Eucommia ulmoides Oliv. (EU) is a small tree and EU extract is widely used to improve hypertension in East Asia. However, its major constituents have poor absorption and stay in the gut for a long time. The role of the gut microbiota in the anti-hypertensive effects of EU is unclear. Here, we examined the anti-hypertensive effects of EU in high-salt diet and N(omega)-nitro-L-arginine methyl ester (L-NAME) induced mice. After receiving EU for 6 weeks, the blood pressure was significantly reduced and the kidney injury was improved. Additionally, EU restored the levels of inflammatory cytokines, such as serum interleukin (IL)-6 and IL-17A, and renal IL-17A. The diversity and composition of the gut microbiota were influenced by administration of EU; 40 significantly upregulated and 107 significantly downregulated amplicon sequence variants (ASVs) were identified after administration of EU. ASV403 (Parabacteroides) was selected as a potential anti-hypertensive ASV. Its closest strain XGB65 was isolated. Furthermore, animal studies confirmed that Parabacteroides strain XGB65 exerted anti-hypertensive effects, possibly by reducing levels of inflammatory cytokines, such as renal IL-17A. Our study is the first to report that EU reduces blood pressure by regulating the gut microbiota, and it enriches the Parabacteroides strain, which exerts anti-hypertensive effects. These findings provide directions for developing novel anti-hypertensive treatments by combining probiotics and prebiotics.

Objectives This study reports the life satisfaction of middle-aged and elderly patients who had a stroke in China, and explores its association with patients’ sociodemographic characteristics, health status, lifestyles and family relationship.Design Cross-sectional survey.Setting and participants The samples of this study were selected from the data of China Health and Retirement Longitudinal Study (CHARLS) in 2018, which covered 28 provinces, 150 countries/districts and 450 village/urban communities. 1154 patients who had a stroke aged 45 and over were included in this study as qualified samples.Outcome measures Descriptive analysis was used to report sociodemographic characteristics, health status, lifestyles, family relationship and life satisfaction of middle-aged and elderly patients who had a stroke. χ2 analysis and binary logistic regression were used to analyse the factors influencing the life satisfaction of the patients who had a stroke.Results Overall, 83.1% of patients who had a stroke were satisfied with their lives, although only 8.7% rated their own health as being good. Patients who had a stroke who were male, elderly, married, living with their spouses and having a pension were more likely to report satisfaction with life (p

BackgroundThis study aims to evaluate the effectiveness of the trial of national multicentric school-based health lifestyles intervention toward childhood obesity on the KBP at individual, family and schools' levels.MethodsThe national trial was a multi-centered, cluster-controlled trial, which was conducted in seven provinces from September 2013 to February 2014, aiming at preventing childhood overweight and obesity. Integrated intervention strategies focused on changing specific practice related to energy intake and expenditure, such as decreasing the consumption of sweetened fizzy drinks, increasing the consumption of vegetables, ensuring proper protein intake, reducing sedentary practice including screen time, and maintaining at least 1 h of moderate to vigorous physical activity. A total of 27,477 children and adolescents in the control group and 30,997 in the intervention group were recruited with a mean follow-up period of 6.7 months. The binomial response mixed-effects model was used for assessing the effects of the national school-based health lifestyles intervention on obesity-related KBP at students individual, parents' and schools' levels.ResultsChildren and adolescents in the intervention group mastered better obesity-related knowledge, and they had higher correct response rates to all questions about obesity-related knowledge compared to the control group (P < 0.05). In terms of obesity-related belief, individuals in the intervention group was more motivated than the control group, participants in the intervention group had higher correctness of 71.18, 52.94, and 56.60% than the control group of 68.61, 49.86, and 54.43%, (P < 0.05). In addition, healthier habits of eating breakfast and drinking milk every day were observed in the intervention group. For the beliefs toward obesity, parents of the intervention group had higher correctness than the control group. At the same time except for the fruit consumption, other obesity-related practice in the intervention group were healthier than the control group (P < 0.05). Except for some beliefs and practice, the intervention effect at the parent level was not significant in other aspects.ConclusionThe obesity-related knowledge and beliefs of children and adolescents got improved significantly. However, the effects on the knowledge, beliefs and certain practices of their parents and school administrators failed to reach significance.

BackgroundMetabolically healthy obesity (MHO) is a group of subjects with overweight/obesity who present a metabolically healthy profile; however, associated factors are complex and are far from completely understood. The aim of the current study was to estimate the prevalence of different metabolic body size phenotypes and investigate the associated factors in Chinese children and adolescents.MethodsA cross-sectional survey was conducted of 12,346 children and adolescents aged 7–18 years from seven provinces in China in 2013. Anthropometric, blood pressure, and biochemical measurements were obtained. A multi-component questionnaire covering demographic, neonatal, and lifestyle characteristics was administered. The classification of metabolic body size phenotype based on three definitions was compared. With metabolically healthy with normal weight (MHNW) as a reference group, logistic regression analyses were used to estimate the potential effects of associated risk factors, with adjustment for age, sex, single-child status, and residence area.ResultsThe prevalence of MHNW, MHO, metabolically unhealthy with normal weight (MUNW), and metabolically unhealthy overweight/obesity (MUO) phenotype was 68.6%, 2.0%, 26.4%, and 3.0%, respectively. There were 39.3% MHO and 60.7% MUO among obese participants and 72.2% MHNW and 27.8% MUNW among those with normal weight. Compared to cardiometabolic risk factor (CMRF) criteria and metabolic syndrome (MetS) component definition, the application of the 2018 consensus-based definition may identify more children with abnormal cardiovascular risks, independent of weight status. Compared to younger children, older-aged adolescents were positively associated with higher risks of MUNW (odds ratio (OR) = 1.38, 95% CI = 1.27–1.50) and MUO (OR = 1.29, 95% CI = 1.04–1.60), while factors positively associated with MHO were younger age, single-child status, urban residence, high birth weight, prolonged breastfeeding duration, parental overweight/obesity status, long screen time, and less physical activity.ConclusionThere were still a high proportion of children and adolescents at high cardiometabolic risk in China. Our findings reinforce the need for cardiometabolic risk prevention in children and adolescents irrespective of their weight statuses, such as parental educational programs and healthy lifestyle interventions.

IntroductionThe relationship between the characteristics of puberty growth and the stature (height and overweight and obesity) in late adolescence was not clear. We aimed to explore the effects of puberty growth patterns on the stature in late adolescence.MethodsA total of 13,143 children from a longitudinal cohort from 2006 to 2016 in Zhongshan city of China were included. The Preece–Baines growth curve was fitted for each individual child, and the age at peak height velocity (APHV), peak height velocity (PHV), and age at take-off (TOA) were obtained from the Preece–Baines model. To compare the difference in height in late adolescence (at 18 years old) at different pubertal height growth patterns (height spurt timing, intensity, and duration), the height at baseline was matched by using the propensity score matching. The log-binomial model was applied to assess the association between the three pubertal height growth patterns (timing, intensity, and duration) and overweight and obesity status in late adolescence, controlling the urbanity and body mass index (BMI) at baseline.ResultsAfter matching the baseline height, boys and girls in three pubertal patterns with early timing (P < 0.01), small intensity (P < 0.01), and short duration (P < 0.01) of height spurt had the lowest final height in the late adolescence. A 16% increase and 45% increase of risk for overweight and obesity were significantly associated with the early APHV in boys and girls, respectively, relative risk (RR) in boys, 1.16(95% confidence interval, CI: 1.03–1.30), P = 0.011; RR in girls, 1.45(1.21–1.75), P < 0.001. A 21% increase and 59% increase of risk for overweight and obesity were significantly associated with small PHV in boys and girls, respectively, RR in boys, 1.21(1.07–1.36), P < 0.001; RR in girls, 1.59(1.30–1.95), P < 0.001; and an 80% increase of risk for overweight and obesity with small spurt duration in girls (RR = 1.80; 95% CI: 1.49, 2.18; P < 0.001).ConclusionPubertal growth patterns, including earlier puberty onset timing, smaller puberty intensity, and shorter puberty spurt duration, had a positive association with lower height risks and higher overweight and obesity risks in late adolescence.