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Abstract As an autoimmune disease, the persistent systemic inflammatory response associated with connective tissue disease (CTD) is involved in the development of venous thromboembolism (VTE). However, clinical data showed that the risk of VTE in patients differed between subtypes of CTD, suggesting that different subtypes may have independent mechanisms to promote the development of VTE, but the specific mechanism lacks sufficient research at present. The development of pulmonary fibrosis also contributes to the development of VTE, and therefore, patients with CTD-associated interstitial lung disease (CTD-ILD) may be at higher risk of VTE than patients with CTD alone or patients with ILD alone. In addition, the activation of the coagulation cascade response will drive further progression of the patient’s pre-existing pulmonary fibrosis, which will continue to increase the patient’s risk of VTE and adversely affect prognosis. Currently, the treatment for CTD-ILD is mainly immunosuppressive and antirheumatic therapy, such as the use of glucocorticoids and janus kinase-inhibitors (JAKis), but, paradoxically, these drugs are also involved in the formation of patients’ coagulation tendency, making the clinical treatment of CTD-ILD patients with a higher risk of developing VTE challenging. In this article, we review the potential risk factors and related mechanisms for the development of VTE in CTD-ILD patients to provide a reference for clinical treatment and prevention.

IntroductionIschemic stroke patients commonly experience disorder of consciousness (DOC), leading to poorer discharge outcomes and higher mortality risks. Therefore, the identification of applicable electrophysiological biomarkers is crucial for the rapid diagnosis and evaluation of post-stroke disorder of consciousness (PS-DOC), while providing supportive evidence for cerebral neurology.MethodsIn our study, we conduct microstate analysis on resting-state electroencephalography (EEG) of 28 post-stroke patients with awake consciousness and 28 patients with PS-DOC, calculating the temporal features of microstates. Furthermore, we extract the Lempel-Ziv complexity of microstate sequences and the delta/alpha power ratio of EEG on spectral. Statistical analysis is performed to examine the distinctions in features between the two groups, followed by inputting the distinctive features into a support vector machine for the classification of PS-DOC.ResultsBoth groups obtain four optimal topographies of EEG microstates, but notable distinctions are observed in microstate C. Within the PS-DOC group, there is a significant increase in the mean duration and coverage of microstates B and C, whereas microstate D displays a contrasting trend. Additionally, noteworthy variations are found in the delta/alpha ratio and Lempel-Ziv complexity between the two groups. The integration of the delta/alpha ratio with microstates’ temporal and Lempel-Ziv complexity features demonstrates the highest performance in the classifier (Accuracy = 91.07%).DiscussionOur results suggest that EEG microstates can provide insights into the abnormal brain network dynamics in DOC patients post-stroke. Integrating the temporal and Lempel-Ziv complexity microstate features with spectral features offers a deeper understanding of the neuro mechanisms underlying brain damage in patients with DOC, holding promise as effective electrophysiological biomarkers for diagnosing PS-DOC.

Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted and associated with oxidative stress, unbalanced gut microbiota, and aberrant immune response. Indeed, oxidative stress can affect the progression and development of IBD by regulating the homeostasis of the gut microbiota and immune response. Therefore, redox-targeted therapy is a promising treatment option for IBD. Recent evidence has verified that Chinese herbal medicine (CHM)-derived polyphenols, natural antioxidants, are able to maintain redox equilibrium in the intestinal tract to prevent abnormal gut microbiota and radical inflammatory responses. Here, we provide a comprehensive perspective for implementing natural antioxidants as potential IBD candidate medications. In addition, we demonstrate novel technologies and stratagems for promoting the antioxidative properties of CHM-derived polyphenols, including novel delivery systems, chemical modifications, and combination strategies.

Background. There has been a gradual trend towards younger ageing of acute cerebral infarction in recent years. Atherosclerotic plaque rupture followed by dislodgement of emboli and resulting arterial embolism is an important mechanism for the development of acute cerebral infarction. Traditional independent risk factors for cerebral infarction have received attention from clinicians, but the risk factors for large artery atherosclerotic cerebral infarction are still unclear. Various blood biomarkers have an important role in the early diagnosis of large artery atherosclerotic cerebral infarction. Objective. To assess the diagnostic predictive value of a group of biomarkers for large artery atherosclerotic cerebral infarction. Methods. Lipoprotein-associated phospholipase A2 (LP-PLA2), trypsin-like protein (TPS), serum amyloid A (SAA), and supersensitive C-reactive protein (hs-CRP) levels were measured in the case group (30 cases) and control group (54 cases), respectively. Results. The differences in the general data between the two groups were not statistically significant (P>0.05). Logistic regression and ROC curve analysis showed that Lp-PLA2, TPS, and SAA were positively associated with the diagnosis of large atherosclerotic cerebral infarction (P

Polyphenols and their derivates, a kind of natural product distributed in herb plants, vegetables, and fruits, are the most abundant antioxidants in the human diet and have been found to display cancer-preventative effects in several epidemiological studies. The scientific community has also validated the anti-cancer bioactivities and low toxicities of polyphenolic compounds, including flavones, tannins, phenolic acids, and anthocyanins, through in vitro and in vivo studies. However, the low stability, weak targeting ability, poor solubility, and low bioavailability of pure polyphenolic agents have significantly impaired their treatment efficacy. Nowadays, nano-based technology has been applied to surmount these restrictions and maximize the treatment efficacy of polyphenols. In this review, we summarize the advantages and related mechanisms of polyphenols in cancer treatment. Moreover, aiming at the poor solubility and low bioavailability of pure polyphenols in vivo, the advantages of nano-based delivery systems and recent research developments are highlighted. Herein, particular emphasis is mainly placed on the most widely used nanomaterials in the delivery of natural products, including liposomes, micelles, and nanogels. Finally, we present an overview and the challenges of future implementations of nano-based delivery systems of polyphenolic compounds in the cancer therapeutic field.

Peroxiredoxin 6 (PRDX6) is widely distributed in several organs, especially the lungs. The role of PRDX6 in oxidative stress is controversial and even contradictory, as indicated by research conducted over the past 20 years. PRDX6 has anti-oxidant or pro-oxidant effects on oxidative stress in different diseases. It can even exhibit both anti-oxidant and pro-oxidant effects in the same disease. These findings are attributed to the fact that PRDX6 is a multifunctional enzyme. The peroxidase and phospholipase A2 activity of PRDX6 is closely related to its anti-oxidant and pro-oxidant effects, which leads to the conflicting regulatory effects of PRDX6 on oxidative stress in respiratory diseases. Moreover, PRDX6 interacts with multiple redox signaling pathways to interfere with cell proliferation and apoptosis. PRDX6 has become a new target in respiratory disease research due to its important regulatory role in oxidative stress. In this paper, the role of PRDX6 in oxidative stress in respiratory diseases and the research progress in targeting PRDX6 are reviewed.

Abstract Background The reference values of eNO have certain differences among people of different countries and races. We aimed to obtain the reference value of eNO in healthy children and adolescents (6–18 years old) in China and to explore the associations between the reference values with ages, gender, heights, BMI, and regions. Methods We measured FeNO50 levels in 5949 healthy Chinese children and adolescents, FeNO200 and CaNO levels in 658 participants from 16 provinces of 7 administrative areas in China aged 6–18. All persons were studied after obtaining informed consent from children and their parents. Results The mean FeNO50 of 5949 Chinese children and adolescents aged 6–18 years was 14.1 ppb, with a 95% confidence interval of 1-38.1 ppb. The mean FeNO200 of 658 persons was 6.9 ppb with a 95% upper confidence interval of 15.0 ppb, and the mean CaNO was 3.0 ppb with a 95% upper confidence interval of 11.2 ppb. In the 6–11 age group, age and height were correlated with the logarithm of FeNO50 (P 0.05). The logarithm of CaNO was correlated with gender (P

Abstract Background The high prevalence of sensory impairment and functional limitations in older adults is a significant concern, yet there is limited understanding of the relationship between these two conditions. Therefore, the objective of this study was to investigate the pathways connecting sensory impairment and functional limitations by examining serial multiple mediating effects of social isolation and cognition in older adults. Methods Using the China Health and Retirement Longitudinal Study dataset, a sample of 4871 older adults was selected. The study variables included sensory impairment, functional limitations, social isolation and cognition, and other covariates. A hierarchical multiple linear regression model was used to assess the association between sensory impairment and functional limitations. Mediation analysis was conducted to explore the sequential multiple mediating effects of social isolation and cognitive function in the relationship between sensory impairment and functional limitations. Results Our findings revealed a significant and positive association between sensory impairment and functional limitations (B = 0.615, 95% CI: 0.397, 0.834). After adjusting for social isolation and cognitive function, the impact of sensory impairment on functional limitations accounted for 87.19% of the total effect. Additionally, approximately 12.81% of the significant relationship between dual sensory impairment and functional limitations was mediated by social isolation and cognitive function. A serial multiple mediating pathway (sensory impairment → social isolation → cognition → functional limitations) was identified, with a coefficient of 0.013 (95% CI: 0.006, 0.020). Conclusions Our study provides evidence for the mediating effects of social isolation and cognition in the relationship between sensory impairment and functional limitations. Given the prevalence of functional limitations among older adults with sensory impairment, it is crucial to consider social isolation and cognitive function in efforts to reduce the burden of disability care. Future validation of these findings through longitudinal studies is necessary.

BackgroundExercise-induced oxidative stress and inflammation can impair muscular function in humans. The antioxidant and anti-inflammatory properties of molecular hydrogen (H2) highlight its potential to be as an effective nutritional supplement to support muscular function performance in healthy adults. However, the effects of H2 supplementation on muscular endurance performance in trained individuals have not been well characterized. This study aimed to assess the effects of intermittent hydrogen-rich water (HRW) supplementation before, during, and after resistance training on muscular endurance performance, neuromuscular status, and subjective perceptual responses after a 48-h recovery period.MethodsThis randomized, double-blinded, placebo-controlled cross-over study included 18 trained men aged 19.7 ± 0.9 years. Participants in this study were instructed to consume 1,920 mL of HRW or pure water (Placebo) daily for 7 days. Additionally, participants were required to supplement with HRW or pure water five times during the training day (1,260 mL total). This included drinking 210 mL 30 min and 1 min before training, 210 mL between training sets, 210 mL immediately after training, and 420 mL 30 min into the recovery period. Participants performed half-squat exercises with the load set at 70% of one repetition maximum for six sets (half-squat exercise performed to repetitions failure each set). We measured the power output and number of repetitions in the free barbell half-squat used to assess muscular endurance performance in participants. The countermovement jump (CMJ) height, total quality recovery scale (TQRS), and muscle soreness visual analog scale (VAS) scores were measured to assess fatigue recovery status after training, as well as at 24 and 48 h of recovery.ResultsThe total power output (HRW: 50,866.7 ± 6,359.9W, Placebo: 46,431.0 ± 9,376.5W, p = 0.032) and the total number of repetitions (HRW:78.2 ± 9.5 repetitions, Placebo: 70.3 ± 9.5 repetitions, p = 0.019) in the H2 supplemented group were significantly higher than in the placebo group. However, there was no statistically significant difference (p< 0.05) between the H2 and placebo groups in CMJ, TQRS, and VAS.ConclusionEight days of intermittent HRW intake could significantly improve muscular endurance performance in trained individuals, making it a promising strategy for athletes or fitness enthusiasts looking to boost muscular endurance during resistance training or competitions. However, it should be noted that HRW intake alone may not be adequate to accelerate recovery from muscle soreness or fatigue following high-intensity training.

The growth of root system directly affects the absorption and utilization of soil water and nitrogen, and understanding the responses of root characteristics to water and nitrogen regimes is thus crucial for optimizing water and nitrogen management. The root characteristics of each soil layer, i.e., root length, root surface area, and root volume, as well as fruit yield and water use efficiency of greenhouse tomato under drip fertigation in response to different irrigation levels and nitrogen rates were explored in northwest China. There were four irrigation levels, i.e., 50% ETC (W1), 75% ETC (W2), 100% ETC (W3), and 125% ETC (W4), where ETC is the crop evapotranspiration, and four nitrogen rates, i.e., 0 kg ha−1 (N1), 150 kg ha−1 (N2), 250 kg ha−1 (N3), and 350 kg ha−1 (N4). The results showed that reasonable irrigation and nitrogen regimes (W3N3) significantly increased fruit yield by 31.64% and root length, root surface area, and root volume by 45.03%, 61.24%, and 148.21% compare to W3N1, respectively. The promoting effect of increasing irrigation level on root characteristics increased with soil depth and had the greatest increases in root volume by 27.07%, 123.43%, and 211.47% for the 0–10, 10–20, and 20–30 cm soil layers, respectively. In addition, reducing irrigation level significantly increased the percentages of roots in the top soil by 29.71%, 26.77%, and 18.53% for root length, root surface area, and root volume, respectively. The reasonable nitrogen rate (N3) significantly increased fruit yield by 41.11%, water use efficiency by 34.42%, and root length, root surface area, and root volume by 40.42%, 41.44%, and 112.76%, respectively. The over-application of nitrogen (N4) reduced root characteristics of all soil layers, fruit yield, and water use efficiency. The promoting effect of increasing nitrogen rate on root length of each soil layer decreased with soil depth, by 71.01%, 48.96%, and 15.71% for 0–10, 10–20, and 20–30 cm soil layers, respectively. Irrigation level was the main factor dominating the root growth of each soil layer. The correlation analysis showed that fruit yield had significantly positive correlations with root characteristics in all soil layers, while water use efficiency had significantly positive correlations with the percentages of root length and root surface area in the 0–10 cm soil layer. In conclusion, rational water and nitrogen regimes achieved better fruit yield by promoting root growth of greenhouse tomato, and the water use efficiency of greenhouse tomato was improved by increasing the root percentage in the topsoil layer to alleviate the adverse effects under water stress conditions. This study reveals how irrigation volume and nitrogen application can enhance tomato yield and water use efficiency by regulating root characteristics and vertical root distribution, providing support for understanding the response of root systems to changes in soil water and nitrogen conditions.

The autonomous lane change maneuver is a critical component in the advancement of intelligent transportation systems (ITS). To enhance safety and efficiency in dynamic traffic environments, this study introduces a novel autonomous lane change strategy leveraging a quintic polynomial function. To optimize the trajectory, we formulate an objective function that balances the time required for lane changes with the peak acceleration experienced during the maneuver. The proposed method addresses key challenges such as driver discomfort and prolonged lane change durations by considering the entire lane change process rather than just the initiation point. Utilizing a fifth-order polynomial for trajectory planning, the strategy ensures smooth and continuous vehicle movement, reducing the risk of collisions. The effectiveness of the method is validated through comprehensive simulations and real-world vehicle tests, demonstrating significant improvements in lane change performance. Despite its advantages, the model requires further refinement to address limitations in mixed traffic conditions. This research provides a foundation for developing intelligent vehicle systems that prioritize safety and adaptability.

Background: Hypertension has emerged as a chronic disease prevalent worldwide that may cause severe cardiovascular complications, particularly in older patients. However, there is a paucity of studies that use risk factors and prediction models for cardiovascular complications associated with hypertension in older adults. Objectives: To identify the risk factors and develop prediction models for cardiovascular complications among older patients with hypertension. Methods: A convenience sample of 476 older patients with hypertension was recruited from a university-affiliated hospital in China. Demographic data, clinical physiological indicators, regulatory emotional self-efficacy, medication adherence, and lifestyle information were collected from participants. Binary logistic regression analysis was performed to screen for preliminary risk factors associated with cardiovascular complications. Two machine learning methods, Back-Propagation neural network, and random forest were applied to develop prediction models for cardiovascular complications among the study cohort. The sensitivity, specificity, accuracy, receiver operating characteristic curve, and area under the curve (AUC) values were used to assess the performance of the prediction models. Results: Binary logistic regression identified nine risk factors for cardiovascular complications among older patients with hypertension. The machine learning models displayed excellent performance in predicting cardiovascular complications, with the random forest model (AUC 0.954) outperforming the Back-Propagation neural network model (AUC 0.811), as confirmed by model comparison analysis. The sensitivity, specificity and accuracy of the Back-Propagation neural network model compared to the random forest model were 74.2% vs. 86.5%, 75.2% vs. 94.3%, and 74.7% vs. 90.4%, respectively. Conclusion: The machine learning methods employed in this study demonstrated feasibility in predicting cardiovascular complications among older patients with hypertension, with the random forest model based on nine risk factors exhibiting excellent prediction performance. These models could be used to identify high-risk populations and suggest early interventions aimed at preventing cardiovascular complications in such cohorts.

Abstract Background Currently, there are few such studies about establishing the frailty prediction model on the basis of the research on the factors influencing frailty in older patients, which can better predict frailty and identify its risk factors, and then guide the formulation of intervention measures precisely, especially in the hospital setting in China. Meanwhile, comprehensive geriatric assessment (CGA) can provide measurable and substantial health improvements for frail older people. The study aimed to develop a nomogram model for frailty risk among hospitalised older people using CGA data and validated its predictive performance for providing a basis for medical staff to grasp the risk and risk factors of older inpatients’ frailty conveniently and accurately, and to formulate reasonable nursing intervention plan. Methods We used CGA data of individuals over age 64. Demographic characteristics, geriatric syndrome assessment, and frailty assessment based on the FRAIL scale were included as potential predictors. Significant variables in univariate analysis were used to construct risk models by logistic regression analysis. We used the root mean square (rms) to develop the nomogram prediction model for frailty based on independent clinical factors. Nomogram performance was internally validated with Bootstrap resampling. The final model was externally validated using an independent validation data set and was assessed for discrimination and calibration. Results Data from 2226 eligible older inpatients were extracted. Five hundred sixty-two older inpatients (25.25%) suffered from frailty. The final prediction model included damaged skin, MNA-SF, GDS-15, Morse risk scores, hospital admission, ICI-Q-SF, Braden score, MMSE, BI scores, and Caprini scores. The prediction model displayed fair discrimination. The calibration curve demonstrated that the probabilities of frailty predicted by the nomogram were satisfactorily matched. Conclusions The prediction model to identify hospitalised older people at high risk for frailty using comprehensive geriatric assessment data displayed fair discrimination and good predictive calibration. Therefore, it is inexpensive, easily applied, and accessible in clinical practice, containing variables routinely collected and readily available through consultation. It will be valuable for grasp older inpatients at high risk of frailty and risk factors in hospital setting to guide the formulation of intervention measures precisely for reversing and preventing frailty.

Abstract Aim To evaluate role function and job satisfaction, determine their relationship, and explore the factors influencing job satisfaction among community nurses in China. Design Cross‐sectional study. Methods This study was conducted between March and June 2020 on a cluster random sampling of 302 community nurses from 24 community health centres and stations in Xi'an, China. Self‐reported data were collected using the Demographics Questionnaire, Role Function of Community Nurses Questionnaire, and Job Satisfaction of Community Nurses Scale. Descriptive statistics, Pearson's correlation analysis, and multiple linear regression analyses were performed to analyse data. Results Community nurses' main role function was organiser and manager (M = 2.56, SD = 0.987) and coordinator (M = 2.43, SD = 0.971). The lowest job satisfaction was for salary and benefits (M = 3.12, SD = 0.891) and personal development (M = 3.65, SD = 0.738). A positive correlation was found between the roles of caregiver, educator, navigator, and salary and benefits (p

Introduction: Clear aligners, while offering a more hygienic alternative to fixed appliances, are still associated with challenges including plaque accumulation and enamel demineralization. The aim of the present study was to investigate the antibiofilm and remineralization effectiveness of innovative flowable composite attachments containing bioceramic micro-fillers.Methods: Four experimental attachments were formulated and bonded to human enamel specimens: 3M Filtek Supreme flowable composite (Filtek SF) + 10% bioactive glass 45S5 (BAG), Filtek SF + 30% BAG, Filtek SF + 10% Bredigite (BRT), Filtek SF + 30% BRT. Plaque biofilms were grown on the bonded enamel using a standardized protocol and the biofilm-killing effect was assessed by confocal laser scanning microscopy and scanning electron microscopy. Vickers microhardness was measured to evaluate the remineralization effect of the attachments containing bioceramic fillers after acid challenge. Shear bond test was performed to assess the bonding strength.Results: Attachments with bioceramic fillers significantly inhibited plaque biofilm growth in 3 weeks on enamel, contributing over 20% bacterial cell killing in 10% filler groups and over 30% killing in 30% filler groups. All four experimental groups demonstrated significantly higher microhardness values than the control group without fillers on the attachment side. The shear bonding strength was not compromised in the attachments with micro-fillers.Discussion: Proper incorporation of bioceramic micro-fillers in attachments provides an innovative approach for clear aligner therapy with reinforced antibiofilm and remineralization effects without weakening shear bonding strength.

AbstractD-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a commonly used nonionic surfactant used as a pharmaceutical carrier in different drug delivery systems. TPGS can reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) and also has anticancer activities. It suggests that when designing antitumor drug preparation, it’s necessary to take into account the antitumor activity of TPGS. Our in vivo studies showed that TPGS exerted the strongest cytotoxicity in MCF-7-ADR cells when compared with seven other tumor cell lines. The further study revealed TPGS caused apoptosis and blocked MCF-7 cell growth in G2/M phase. Mechanistic insights suggested that TPGS increased intracellular calcium ion concentrations, leading to apoptosis via the mitochondrial pathway. Furthermore, two in vivo experiments were performed. One was TPGS, and DOX solution was administered by tail vein injection on MCF-7-ADR tumor bearing nude mice. The other was temperature sensitive TPGS gel (TPGS-TG) was administered by intratumoral injection on MCF-7-ADR tumor bearing nude mice combined with paclitaxel albumin nanoparticles (Abraxane®) administered by tail vein injection. The findings confirmed that TPGS could play its role in anti-tumor to reduce the toxicity of chemotherapeutic drugs and improve the efficiency of drug-resistant tumors, thereby enhancing the development of safe oncology therapeutics.

Abstract Objective To establish the predicted value of pulmonary function determined by impulse oscillometry (IOS) in children (4–17 years old) in China. Methods A total of 6270 healthy children aged 4–17 years in China were included. The Master Screen IOS pulmonary function device (Jaeger Co, Germany) was used to detect the respiratory impedance (Zrs), resonant frequency (Fres), respiratory system resistance (Rrs) and respiratory system reactance (Xrs) at various oscillation frequencies, and the indices above were analysed. Stepwise multivariate regression was used to establish the regression equation of related parameters of IOS in different sexes, ages, height, and weight. Results The differences in the main IOS parameters between different age stages were statistically significant regardless of sex (P

Abstract Background Guillain–Barre syndrome (GBS) is a rare neurological complication of brucellosis, and neurobrucellosis is the most common, but they have many similarities in clinical manifestations. Many clinicians are accustomed to merely explaining the manifestations of nervous system involvement with neurobrucellosis, but they ignore the possibility of GBS, and this leads to misdiagnosis, untimely treatment, and serious consequences. Case presentation A 55-year-old male patient was admitted to The First Affiliated Hospital of Harbin Medical University for intermittent fever, fatigue, and waist pain more than three months. Brucellosis was diagnosed from the blood test. Although anti-brucella treatment was given at the time of diagnosis, the disease continued to progress. At the time of the cerebrospinal fluid systematic physical examination and the neuroelectrophysiological test, acute motor sensory axonal neuropathy was diagnosed. The patient was given immediately administered immunoglobulin therapy. After three months of systemic treatment, the patient's muscle strength of the distal limbs gradually recovered. The numbness of the limbs eased slowly, and urination function and respiratory function returned to normal. He could sit by himself. Conclusions The possibility of GBS should be closely monitored for when a brucellosis patient shows typical clinical manifestations of progressive muscle weakness, protein-cell separation of the cerebral spinal fluid, and typical demyelinating sensorimotor polyneuropathy.

BackgroundMental health is a global issue requiring global attention. Depression and anxiety are two of the most common mental disorders (CMDs) and are characterized by high incidence and high comorbidity. In recent years, the prolonged COVID-19 pandemic and exacerbated social instability have posed significant challenges to the mental resilience and mental health outcomes of the global population. Now more than ever, with an increase in mental health needs, it has become even more crucial to find an effective solution to provide universal mental healthcare. Psychotherapy is of vital importance for those coping with symptoms of depression and anxiety and is used to enhance mental resilience. However, such therapy can be difficult to access in reality. In this context, the Micro-Video Psychological Training Camp (MVPTC) platform will be developed.ObjectivesAs an online self-help platform for psychological intervention, the MVPTC platform was developed for those who suffer from mild to moderate symptoms of depression and/or anxiety and is tasked with the goal of reducing depressive and anxious symptoms while improving mental resilience. Thus, this study will be carried out to verify its efficacy and applicability.MethodsIn this parallel-group, randomized controlled trial, a total of 200 mild to moderately depressed and/or anxious adults seeking self-help will be randomly recruited and assigned to either the micro-video psychological intervention group or the wait list control group. Online measurements by self-assessment will be taken at baseline, post-intervention, 1-month, and 3-month follow-up.ResultsThe primary results will involve symptoms of depression and anxiety. The secondary results will involve mental resilience. An analysis will be conducted based on the intention-to-treat principle.DiscussionThis trial will examine whether the MVPTC platform for the relief of symptoms and the enhancement of resilience in a population screened for depression and anxiety symptoms proves effective and applicable. Large-scale resilience enhancement may benefit public mental health in terms of preventive interventions, managing depressive and anxiety symptoms, and promoting mental health. With the MVPTC-based method being applied, a brief, efficient, and structured intervention model can potentially be established, having the potential to provide necessary and accessible mental support for an extensive target group.Clinical trial registrationhttp://www.chictr.org.cn/, identifier ChiCTR2100043725.

Abstract Anomaly detection has attracted considerable search attention. However, existing anomaly detection databases encounter two major problems. Firstly, they are limited in scale. Secondly, training sets contain only video‐level labels indicating the existence of an abnormal event during the full video while lacking annotations of precise time durations. To tackle these problems, we contribute a new Large‐scale Anomaly Detection (LAD) database as the benchmark for anomaly detection in video sequences, which is featured in two aspects. 1) It contains 2000 video sequences including normal and abnormal video clips with 14 anomaly categories including crash, fire, violence etc. with large scene varieties, making it the largest anomaly analysis database to date. 2) It provides the annotation data, including video‐level labels (abnormal/normal video, anomaly type) and frame‐level labels (abnormal/normal video frame) to facilitate anomaly detection. Leveraging the above benefits from the LAD database, we further formulate anomaly detection as a fully supervised learning problem and propose a multi‐task deep neural network to solve it. We firstly obtain the local spatiotemporal contextual feature by using an Inflated 3D convolutional (I3D) network. Then we construct a recurrent convolutional neural network fed the local spatiotemporal contextual feature to extract the spatiotemporal contextual feature. With the global spatiotemporal contextual feature, the anomaly type and score can be computed simultaneously by a multi‐task neural network. Experimental results show that the proposed method outperforms the state‐of‐the‐art anomaly detection methods on our database and other public databases of anomaly detection. Supplementary materials are available at http://sim.jxufe.cn/JDMKL/ymfang/anomaly‐detection.html.

ObjectiveWe aimed to study the cut-off values of estimated glomerular filtration rate (eGFR) and the urinary albumin creatinine ratio (UACR) in the normal range for diabetic kidney disease (DKD).MethodsIn this study, we conducted a retrospective, observational cohort study included 374 type 2 diabetic patients who had baseline eGFR ≥60 mL/min/1.73 m2 and UACR 0.05). The discrimination of eGFR at the cut-off value of 84.80 mL/min/1.73 m2 or UACR at 15.5mg/g with the largest Youden’s index was further confirmed in the validation cohort. The decrease rate of eGFR was faster in patients with UACR ≥15.5mg/g (P

Abstract Background The critical role of phosphoinositide 3-kinase (PI3K) activation in tumor cell biology has prompted massive efforts to develop PI3K inhibitors (PI3Kis) for cancer therapy. However, recent results from clinical trials have shown only a modest therapeutic efficacy of single-agent PI3Kis in solid tumors. Targeting autophagy has controversial context-dependent effects in cancer treatment. As a FDA-approved lysosomotropic agent, hydroxychloroquine (HCQ) has been well tested as an autophagy inhibitor in preclinical models. Here, we elucidated the novel mechanism of HCQ alone or in combination with PI3Ki BKM120 in the treatment of cancer. Methods The antitumor effects of HCQ and BKM120 on three different types of tumor cells were assessed by in vitro PrestoBlue assay, colony formation assay and in vivo zebrafish and nude mouse xenograft models. The involved molecular mechanisms were investigated by MDC staining, LC3 puncta formation assay, immunofluorescent assay, flow cytometric analysis of apoptosis and ROS, qRT-PCR, Western blot, comet assay, homologous recombination (HR) assay and immunohistochemical staining. Results HCQ significantly sensitized cancer cells to BKM120 in vitro and in vivo. Interestingly, the sensitization mediated by HCQ could not be phenocopied by treatment with other autophagy inhibitors (Spautin-1, 3-MA and bafilomycin A1) or knockdown of the essential autophagy genes Atg5/Atg7, suggesting that the sensitizing effect might be mediated independent of autophagy status. Mechanistically, HCQ induced ROS production and activated the transcription factor NRF2. In contrast, BKM120 prevented the elimination of ROS by inactivation of NRF2, leading to accumulation of DNA damage. In addition, HCQ activated ATM to enhance HR repair, a high-fidelity repair for DNA double-strand breaks (DSBs) in cells, while BKM120 inhibited HR repair by blocking the phosphorylation of ATM and the expression of BRCA1/2 and Rad51. Conclusions Our study revealed that HCQ and BKM120 synergistically increased DSBs in tumor cells and therefore augmented apoptosis, resulting in enhanced antitumor efficacy. Our findings provide a new insight into how HCQ exhibits antitumor efficacy and synergizes with PI3Ki BKM120, and warn that one should consider the “off target” effects of HCQ when used as autophagy inhibitor in the clinical treatment of cancer.

ABSTRACT Pneumonia is the leading cause of death in children; the pathogens are often difficult to diagnose. In this study, the performance of metagenomic next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) samples from 112 children with confirmed pneumonia has been evaluated. mNGS performed a significantly higher positive detection rate (91.07%, 95% confidence interval [CI] 83.80% to 95.40%) and coincidence rate against the final diagnosis (72.32%, 95% CI 62.93% to 80.15%) than that of conventional methods (70.54%, 95% CI 61.06% to 78.58% and 56.25%, 95% CI 46.57% to 65.50%, respectively) (P < 0.01 and P < 0.05, respectively). Bacteria, viruses, and their mixed infections were common in children with pneumonia. Streptococcus pneumoniae was the most common bacterial pathogen in children with pneumonia, while Haemophilus parainfluenzae and Haemophilus influenzae seemed more likely to cause nonsevere pneumonia in children. In contrast, human cytomegalovirus (CMV) infection and the simultaneous bacterial infections could cause severe pneumonia, especially in children with underlying diseases. After adjustments of antibiotics based on mNGS and conventional methods, the conditions improved in 109 (97.32%) children. mNGS of BALF samples has shown great advantages in diagnosing the pathogenic etiology of pneumonia in children, especially when considering the limited volumes of BALF and the previous use of empirical antibiotics, contributing to the timely adjustment of antibiotic treatments, which can potentially improve the prognosis and decrease the mortality. IMPORTANCE Our study indicates high efficiency of mNGS using BALF for the detection of causative pathogens that cause pneumonia in children. mNGS can be a potential diagnostic tool to supplement conventional methods for children’s pneumonia.